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Abstract Introduction: Knee osteoarthritis is a debilitating disease that has been increasing in prevalence, especially due to the aging population and rising incidence of obesity. Biological therapies (orthobiologics) have emerged, demonstrating efficacy in improving functional scores, including the injection of microfragmented Adipose Tissue (mFAT). The purpose of this study is to evaluate the safety of adipose tissue harvesting and mFAT injection under local anesthesia. Materials/methods: A case series involving 34 patients who underwent adipose tissue collection from the abdomen under local anesthesia, without sedation, in a sterile environment, and who received the infiltration of microfragmented adipose tissue after single-time preparation, using a fat washing and microfragmentation kit. Results: Evaluation was performed at the time of the procedure and after 7 days of follow-up. Only ecchymosis (76.5 %) and mild discomfort at the harvested site (70.6 %), as well as mild discomfort at the infiltrated knee (61.8 %), were identified. No major adverse events were identified. Conclusion: The harvesting and injection of mFAT under local anesthesia is safe, with no major adverse events identified during this procedure.

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Abstract Introduction: Cervical Human Papillomavirus (HPV) infection, a common sexually transmitted infection, can lead to cervical cancer. This study investigates the impact of Photodynamic Therapy (PDT) on cellular immune function in cervical HPV-infected patients. Methods: From October 2022 to February 2023, 60 patients with cervical HPV infection were randomly assigned to a control group (conventional treatment) or a PDT group (PDT treatment), each with 30 patients. Peripheral blood samples and cervical tissue were collected before treatment, at 3 months, and at 6 months post-treatment. Flow cytometry assessed T-cell subsets (CD4+, CD8+, CD3+), and ELISA measured cytokine levels (TNF-α, IL-6, IL-8). Results: Baseline characteristics were similar between the PDT and control groups. The PDT group showed significantly higher HPV clearance rates at 3-months (70.00 %) and 6 months (100.00 %) compared to the control group 43.33 % and 80.00 %, respectively (p < 0.05). PDT significantly increased CD3+ and CD4+ cell levels at 3- and 6-months post-treatment compared to controls (p < 0.05). CD8+ levels and the CD4+/CD8+ ratio also significantly increased in the PDT group at 6 months. Additionally, PDT significantly reduced IL-6, IL-8, and TNF-α levels at 3- and 6-months post-treatment (p < 0.05). Conclusion: PDT enhances cellular immune function in cervical HPV-infected patients by increasing CD4+ and CD8+ T-cells and reducing pro-inflammatory cytokines. These findings highlight the potential of PDT in modulating immune responses and improving therapeutic strategies for cervical HPV infection.

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Abstract Introduction: The use of Hormone Dosage (HD) in Fine Needle Aspiration Biopsy (FNA) needle washout fluid, introduced in the 1990s, initially aimed at measuring Thyroglobulin (TG). Elevated TG concentration in an extrathyroidal cervical lesion suggests metastases of Well-Differentiated Thyroid Carcinomas (WDTC). Over the years, HD has evolved to incorporate Calcitonin (CT) and Parathormone (PTH), improving sensitivity and specificity in diverse clinical scenarios. Despite varying cutoffs in the literature, existing data underscore significant advancements in diagnostic accuracy. Methods: This paper presents a case series of 762 cervical lesions with FNA cytology and HD in different cervical regions. Results: It was possible to establish the histogenesis of the lesion based on a combination of the FNA cytology and PTH HD findings, so PTH was useful to determine parathyroid origin in all regions, Thyroglobulin (TG) and PTH together provide insights on cell origin in difficult cases. Thyroglobulin (TG) dosage enhances the accuracy of detecting well-differentiated thyroid carcinomas. In post-thyroidectomy by bed lesions, dosages help to determine non-thyroid/parathyroid lesions. Discussion: The case series and review underscore the valuable contribution of HD in fine-needle aspiration for the evaluation of cervical lesions. By integrating HD with cytological, ultrasound, and clinical data, clinicians can enhance the accuracy and specificity of FNA in diagnosing various cervical lesions, ultimately improving patient care and management.

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Abstract Background and aim: Malignant hilar obstruction usually presents in advanced-stage disease with a poor prognosis. Effective biliary drainage is essential for the beginning of palliative chemotherapy. There is a debate on the amount of liver parenchyma that should be drained to achieve clinical success. This study aimed to correlate the volume of liver drained with clinical success rate. Methods: The authors conducted a retrospective study including patients with malignant hilar biliary obstruction who underwent retrograde endoscopic cholangiography for biliary drainage from January 2014 to December 2018. The main outcome was a correlation of clinical success rate with hepatic volume drained. Secondary outcomes were correlation of clinical success rate with the quantity of liver sectors drained and unilateral versus bilateral drainage. Results: 82 patients met inclusion criteria (58.5 % female), with a mean age of 60±13 years. The main cause of hilar obstruction was cholangiocarcinoma (32.9 %) followed by lymph node metastasis (23.2 %). Technical success was achieved in 75 patients (91.5 %), and clinical success in 45 patients (60 %). The authors found a significant correlation between clinical success rate when at least 50 % of viable parenchyma was drained (p = 0.016; OR = 4.15, 95 % CI 1.4–12.5). Considering liver sectors, higher clinical success rates were found when at least 2 sectors were drained (p < 0.001; OR = 8.50, 95 % CI 2.7–26.7). The correlation between unilateral versus bilateral drainage and clinical success was not statistically significant. Conclusion: Drainage of at least 50 % of volume hepatic parenchyma was associated with better outcomes as well as drainage of at least 2 hepatic sectors, regardless of if unilateral or bilateral.

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Abstract Background: Lactylation plays an essential role in pancreatic cancer, but the precise role of lactylated histone in the diagnosis and prognosis of pancreatic cancer remains to be further clarified. Methods: Twenty-one patients diagnosed with pancreatic cancer were enrolled in this study, and the clinico-pathologic characteristics were collected. Lactylation levels of total proteins and histone H3 Lysine-18 (H3K18) of tissues were determined by western blotting and laboratory indicators including serum levels of lactate, Cancer Antigen 19–9 (CA19–9), and Carcinoembryogenic Antigen (CEA) were obtained. Results: Total protein lactylation was found in both pancreatic cancer tissues and para-carcinoma normal tissues, and was more potent in tumor tissues. H3K18la was also highly expressed tumor tissues. Furthermore, H3K18la protein expression correlated positively with serum lactate (r = 0.774, p < 0.001), CA19–9 (r = 0.744, p < 0.001), and CEA (r = 0.589, p < 0.01). The Area Under the Curve (AUC) of H3K18la for the diagnosis of pancreatic cancer was 0.848 in serum (p < 0.001). Conclusion: The present findings suggested that H3K18 may be used as a novel potential biomarker for the diagnosis and prognosis of pancreatic cancer patients.

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Abstract Background: Primary Health Care (PHC) plays a pivotal role in the healthcare system as the initial point of contact for users and patients. In the healthcare area, claims are presented and managed through a web app. It also enables systematic analysis of emerging information to drive continuous improvement. The present objective was to describe the complaints filed at PHC in 2022. Methods: A cross-sectional study was conducted, examining complaints filed by patients in 2022. For inclusion of the complaints, it was established that it had to do with the treatment received by healthcare personnel and that was presented through the web app. Complaint texts signaling dissatisfaction with the information received were subjected to qualitative coding. Results: The study involved 326 users who submitted a total of 358 complaints specifically related to treatment and information. The average age of the participants was 33.5 ± 16.2 years, and the majority were women (72.4 %, n = 236). In 2022, the Cumulative Incidence (CCI) was 55.2 complaints per 100,000 healthcare act and the Complaint Incidence Rate (CIR), defined as the number of complaints/1000 users/year, was 6.5. The prevalence of complaints related to information was 12.4 %. The main reasons for complaints about information were issues related to communication with the patient (79 %), followed by the patient’s disagreement with the techniques applied by healthcare staff (17 %). Conclusions: Results show us the fundamental characteristics of complaints in primary care with respect to the information received by health professionals, not allowing us to know where the authors can influence through interventions or training actions to try to improve.

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Abstract Introduction: The Marginal Mandibular Nerve (MMN), despite being didactically described as being a unique branch of the other branches of the Facial Nerve, has in practice an abundant anatomical variation. Both in relation to its ramifications and the positioning of these in relation to the lower edge of the mandible, as well as its anastomoses along its path, play a fundamental role in the surgical strategy during the approach of this cervicofacial site, and can generate, as underestimated its characteristics, inadvertent injuries and motor consequences to the patient. Objective: To analyze the types of anatomical variations of the MMN in relation to its position, ramification, and distance from reference points, as well as its incidence that could imply technical difficulties in surgery. Methods: A systematic review was conducted in the literature in search of anatomical studies, in vivo or in cadavers, between 1981 and 2024, which described the quantification of the MMN branches, their positioning and peculiarities in relation to anastomoses with other peripheral nerves. Results: 511 hemifaces were studied, with the identification of 290 cases of single nerve, 160 cases of double branch, 54 cases of triple branch, and 7 cases of quadruple branch. Of the 456 nerves that were possible to study, the average distance when superior to the lower limit of the mandible was 1.61 cm, while its lower analysis was 2.53 cm. The branches presented different proportions of presentation in relation to this reference point depending on how many branches it had, being more common to remain below it. Anastomoses were identified between the MMN and the buccal and cervical branch of the Facial Nerve, as well as with the Trigeminal Nerve. Conclusion: The varied presentations of the MMN, both in its anatomical positioning and in the number of branches leads us to question whether the surgical thinking when performing an exploration in this site may not be the reason whythe authors verify several motor complaints superior to described injuries.

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Abstract Background: The study was to investigate circRBM33 in septic acute lung injury (ALI). Methods: Treatment of Murine Lung Epithelial-12 cells (MLE-12) cells was performed using 10 ng/mL Lipopolysaccharide (LPS). circRBM33, miR-15a-5p, and Enhancer of zeste homolog 1 (EZH1) were ascertained through RT-qPCR or Western blot analysis. The viability of MLE-12 cells was measured using the MTT assay, and their rate of apoptosis was ascertained through flow cytometry. B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X (Bax) were determined using Western blot analysis. Oxidative stress levels were assessed with ELISA kits, and levels of malondialdehyde(MDA) content, Superoxide Dismutase (SOD) activity, and glutathione (GSH) were detected. Dual luciferase reporter gene and RIP assays verified the targeting link between miR-15a-5p and circRBM33 or EZH1. The role of circRBM33 in ALI in vivo was determined by performing cecum ligationperforation (CLP) surgery. HE staining, W/D pulmonary edema, and histological damage scores were taken to assess the extent of lung tissue damage. ELISA was performed to determine proinflammatory factors in lung tissue and cells. Results: CircRBM33 downregulation ameliorated ALI-induced edema, apoptotic, and inflammatory reactions in mouse lung tissues. In addition, apoptosis and inflammation mediated by LPS in MLE-12 cells were ameliorated by circRBM33 downregulation, whereas miR-15a-5p knockdown or EZH1 elevation eliminated the action of silencing circRBM33. circRBM33 mediated EZH1 expression by competitive adsorption of miR-15a-5p. Conclusion: CircRBM33 improves ALI in septic mice by targeting the miR-15a-5p/EZH1 axis.

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Abstract Objective: To investigate the effect of Mometasone furoate (Elocon Cream) Nasal Spray (MFNS) treatment on hearing secretory Otitis Media (SOM) in younger children. Methods: Seventy-six children with SOM (ages 5 to 10 years-old) were selected as study subjects and divided into two groups of 38 cases each using a randomized numerical table. The control group was given conventional treatment, and the observation group was treated with MFNS based on the control group. Both groups were treated for 12 weeks. The improvements in clinical symptoms and hearing were compared between the two groups at weeks 4, 8 and 12 of treatment, respectively. Results: The total effective rate of treatment in the observation group was higher than that in the control group. The middle ear resonance frequency of the children in the observation group was higher than that of the control group at weeks 4, 8 and 12 of treatment, and the air-conduction hearing threshold was lower than that of the control group. The total effective rate of the observation group after 12-weeks of treatment was 92.11 %, which was significantly higher than that of the control group (73.68 %). In addition, the T-ETDQ score of the observation group was lower than that of the control group after treatment. Conclusion: MFNS has clinical efficacy in the treatment of SOM in young children, which can improve clinical symptoms, promote the recovery of hearing and eustachian tube function, reduce the local inflammatory response, and improve immune function.

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Abstract Objective: To investigate the clinical and swallowing profiles of patients with post-intubation tracheal or laryngotracheal stenosis requiring tracheostomy prior to surgical or corrective airway interventions. Methods: A retrospective cohort clinical study. Patients who met the inclusion criteria underwent a swallowing evaluation, as well as imaging studies of the neck and chest. At 6 and 12-months after the initial assessment, all patients participated in follow-up speech pathology consultations to evaluate the current state of swallowing and the progress of airway stenosis treatment. Results: Twenty-five patients with a median tracheostomy duration of 30.52 months were assessed. The study found a female predominance (68%) and a high prevalence of subglottic stenosis (44%). Most patients required intubation due to severe acute respiratory failure and airway protection due to a decreased level of consciousness. Imaging revealed additional airway abnormalities, including laryngotracheobronchitis and laryngeal edema. Swallowing assessments showed that 20% had significant dysphagia. After one year, only two patients were successfully decannulated, while others remained tracheostomy dependent. Conclusion: The study underscores the need for personalized, multidisciplinary care for these patients. It finds that while treatments like reconstructive surgeries and the Montgomery T-tube can be effective, complications such as clinical instability and dysphagia can worsen outcomes and extend the need for tracheostomy.

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Abstract Introduction This study aimed to investigate the associations among seizures, clinical characteristics, and brain injury on Magnetic Resonance Imaging (MRI) in infants with Hypoxic Ischemic Encephalopathy (HIE), and to determine whether these findings can predict unfavorable neurodevelopmental outcomes. Method Clinical and electrographic seizures were assessed by amplitude-integrated electroencephalogram, and the extent of brain injury was evaluated by using MRI. At 12‒24 months of age, developmental impairment or death was assessed. Between 2012 and 2020, 143 newborns were admitted for HIE, and 8 infants were excluded from the study. Results Eighty-five infants were diagnosed with greater than moderate HIE and 65 infants underwent therapeutic hypothermia. In addition, 38 infants experienced clinical seizures (clinical seizure group, CSG), 49 infants had electrographic seizures (Electrographic Seizure Group, ESG), and 48 infants had no seizures (no seizure group, NSG). The proportion of infants with neurodevelopmental impairment or death was significantly higher in the CSG than in the NSG (57.7 % and 26.1 %, p = 0.026). A risk factor analysis indicated that cord blood pH (adjusted Odds Ratio [aOR = 0.01]; 95 % Confidence Interval [95 % CI 0.001‒0.38]; p = 0.015) and MRI findings (aOR = 4.37; 95 % CI 1.25‒15.30; p = 0.012) were independently associated with abnormal neurodevelopment, after adjustment. Discussion Clinical seizures in infants with HIE were independently associated with abnormal neurodevelopment. However, cord blood pH and abnormal brain MRI findings were consistently linked to long-term neurodevelopmental outcomes.

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Abstract Background Chronic Obstructive Pulmonary Disease (COPD) is a common chronic respiratory disease with a long course and recurrent symptoms, seriously affecting patients' quality of life. Objectives This study aimed to explore the interventional value of eight-section brocade exercises in combination with comprehensive measures of the physical function status of patients with COPD. Method This is a retrospective study. A total of 94 COPD patients admitted to the studied hospital were divided into two groups according to different intervention methods. The control group was treated with comprehensive intervention, and the research group received eight-section brocade exercises combined with comprehensive intervention. Results After an intervention, the research group exhibited longer exercise endurance time (p < 0.05); the modified Medical Research Council (mMRC) scores and quality of life scores in the research group were lower than those in the control group (p < 0.05); sleep quality scores of the research group being lower than those of the control group (p < 0.05); both groups experienced a decrease in adverse emotion scores, with the research group scoring lower than the control group (p < 0.05); the research group achieving better physical function status than the control group (p < 0.05); the nursing efficiency rate and satisfaction rate in the research group was higher than those in the control group (p < 0.05). Conclusions Eight-section brocade exercises can enhance the exercise endurance of and improve the lung function of COPD patients, which is of great significance for the recovery of patients’ physical function.

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Abstract Objective To investigate the value of Contrast-Enhanced Ultrasound (CEUS) combined with Procalcitonin (PCT) in differentiating Tuberculous Lymph Nodes (TLN) from Metastatic Lymph Nodes (MLN). Methods This prospective cohort study included 207 consecutive patients diagnosed with CTL. Before confirming through pathology or laboratory tests, every patient received standard ultrasound, CEUS, and MRI examinations, with the imaging results analyzed afterward. Serum indicators were measured by Enzyme-Linked Immunosorbent Assay (ELISA). Predictive modeling was performed by multifactorial logistic regression. Evaluate the diagnostic and calibration performance of the predictive model by drawing Receiver Operating Characteristic (ROC) curves and calibration curves, and using Area Under the Curve (AUC) and Hosmer-Lemeshow (H-L) tests. Results The presence of lymph node lesions was confirmed by routine ultrasound and MRI in 207 patients, of which 102 (49.27 %) had a pathological or laboratory diagnosis of metastatic lymph nodes (MLN), and 50.8 % were tuberculous lymph nodes (TLN). According to imaging findings of CEUS, TLN was more commonly associated with enhanced concentric performance in the arterial phase (67.65 % vs. 40.95 %) and heterogeneous enhancement pattern in lymph nodes (70.59 % vs. 52.38 %). Peak Intensity (PI) of lesions was higher in patients with MLN. Increased age-enhanced concentric performance in the arterial phase, increased PI, and serum PCT greater than 5.39 ng/mL were independent risk factors for MLN. The prediction model of serum PCT combined with CEUS had a higher diagnostic value for MLN. The H-L test indicated a satisfactory model fit (all p > 0.05), and the calibration curve closely approximates the ideal diagonal. Conclusion CEUS combined with serum PCT has better clinical application value in the differential diagnosis of TLN and MLN.

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Abstract Objective Based on Toll Like Receptor 4 (TLR4)/Nuclear Factor-κB (NF-κB) Exploring the effects of Licochalcone A (LCA) on the proliferation, invasion, and drug resistance of glioma cells through signaling pathways. Methods Cultivate human glioma cell line U251 in vitro, induce drug-resistant cell line U251/TMZ with Temozolomide (TMZ), and validate the results. Different concentrations of licorice chalcone A were used to treat U251 cells and U251/TMZ cells, and were named as control group, low-dose group, medium-dose group, and high-dose group, respectively. CCK-8 assay, cell adhesion assay, and Transwell assay were used to detect cell survival rate, cell adhesion rate, number of migrating cells, and number of invading cells, respectively. Results The cell survival rate, cell adhesion rate, number of migrating and invading cells in the high-dose group were lower than those in the medium-dose group and lower than those in the control group. High-dose group TLR4, NF-κB mRNA and protein levels were lower than those in the medium dose group and lower than those in the control group (p < 0.05). Compared with the si-NC group, the si-TLR4 group showed a decrease in cell survival rate and adhesion rate, as well as a decrease in the number of migrating and invading cells, the levels of CyclinD1 and N-cadherin proteins decreased, while the levels of E-cadherin protein increased (p < 0.05). Conclusion LCA could inhibit the proliferation and metastasis of glioma cells and reverse drug resistance, possibly by inhibiting the TLR4/NF-κB signaling pathway.

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Abstract Background Gastric Cancer (GC) was the third highest mortality rate among malignant tumors. Currently, no specific treatment is utilized to prevent the progression of GC. The detailed mechanism of GC was still elusive and this study aimed to clarify the mechanism of GC occurrence and development. Method This study was performed to clarify the molecular mechanisms of CST1 promoting GC development through activating AKT. The normal gastric tissue cells and GC cell was obtained, followed by transfection with oe-CST1 or sh-CST1, and their apoptosis and viability were evaluated. Finally, Western blot, Flow cytometry assay, Transwell assay, and Scratch assay were used to elucidate the molecular mechanisms of CST1 promoting GC development through activating the AKT pathway. Results Research outcomes show a significant elevation in CST1 and AKT protein as well as mRNA quantities in both the model and CST1-activator cohorts in relation to the control. Conversely, these proteins and mRNA concentrations were notably decreased in the presence of the CST1 inhibitor when compared to the model group, a difference that was statistically significant as evidenced by the p-value. Conclusion CST1 can promote the gastric cancer process by targeting the AKT pathway.

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ABSTRACT Background Hospitalization for Transurethral Prostate Resection (TURP) involves circadian rhythm disturbance - a possible cause of Postoperative Neurocognitive Disorder (POCD) in elderly patients. This study investigated whether melatonin ameliorated this effect. Methods A double-blind, randomized clinical trial used a battery of neuropsychological tests to evaluate cognitive performance of 118 patients aged ≥ 60, before TURP with spinal anesthesia, and at 21- and 180-days PO. Patients received 10 mg of melatonin, or a placebo, on the night before surgery and 1-, 2- and 3-days PO. Delayed neurocognitive recovery in the two groups at 21 days PO was compared using the Chi-Squared test; individual performances in each test at each date were compared using the General Mixed Model. Results with p < 0.05 were considered significant. Results Pre-surgery, both groups had significant cognitive deficits. Delayed cognitive recovery at 21 days PO was the same in both. There were no cases of POCD at 180 days. The melatonin group performed better in the delayed-recall FOME, which assesses memory, and in the Digit Span test, which assesses attention and cognitive flexibility. Unexpectedly, global neurocognitive performance was improved at 180 PO in both groups. Conclusions Melatonin had no statistical effect on POCD, but a selective beneficial effect was observed in two cognitive areas. The high prevalence of preoperative cognitive impairment may be related to the lower urinary tract symptoms which were reasons for the surgery; the unexpected improvement of cognitive performance in all patients at 180 days PO may reflect alleviation of these symptoms.

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Abstract Mycobacteria infections are caused by species of the Mycobacterium tuberculosis complex (MTB) and other species called Non-Tuberculosis Mycobacteria (NTM). Identification of mycobacteria species is very important to define treatment and it can be achieved by direct culture. However, the lack of clear protocols regarding the use of culture or molecular tests on specimens diagnosed with granulomatous lesions causes delays in the diagnosis of the etiological agents and, consequently, the definition of the right treatment. This work aimed to characterize the incidence of mycobacteria species in pulmonary granulomatous lesions and the contribution of Polymerase Chain Reaction (PCR) in Formalin-Fixed Paraffin-Embedded Tissue (FFPE), direct culture, and Ziehl-Neelsen histological stain to the diagnosis. The authors performed an observational, centralized, and retrospective study in a cohort of 336 cases with pulmonary granulomatous lesions. Mycobacteria were detected by ZNS in 54/323 (16.72 %) and by direct culture in 40/198 (20.20 %). MTB DNA was detected by PCR in 10/57 (17.54 %). Mycobacterial culture results revealed MTB in 26/40 (65.00 %), whereas NTM was detected in 13/40 (32.50 %). NTM was represented by M. avium (n = 4), M. intracellulare (n = 3), M. kansasii (n = 3), M. colombiense (n = 1), M. paraffinicum (n = 1), and M. abscessus subsp. massiliense (n = 1). In conclusion, this study demonstrated that mycobacteria are detected in 16.72 % to 20.20 % of pulmonary granulomatous lesions. Moreover, MTB and NTM were detected in these lesions. The use of different methods for mycobacteria detection, in addition to culture, is complementary and contributes to fastening and increasing the detection of mycobacteria in these lesions.

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Abstract Introduction People Living with Human Immunodeficiency Virus (PLHIV) appear to be at a higher risk of developing sarcopenia. Various factors seem to influence the risk of sarcopenia, and its prevalence may differ depending on the screening tool used. This study aimed to (i) Screen the risk of sarcopenia in PLHIV using the SARC-F and SARC-Calf and identify associated factors; (ii) Analyze the agreement between the instruments in PLHIV. Methods Cross-sectional study including PLHIV taking antiretroviral therapy. The authors assessed sarcopenia risk using the SARC-F and SARC-Calf tools with ≥4 and ≥11 cutoff points, respectively, and a wide spectrum of variables was analyzed. Results Participated 76 patients (44.9 ± 12.7 years). Sarcopenia risk, according to the SARC-F, was 27.6 % and was associated with socioeconomic status (p = 0.004), smoking (p = 0.001), disease status (p < 0.001), opportunistic infections (p = 0.001), CD4 T-cell count (p < 0.001), Handgrip Strength (HGS) (p < 0.001), and Gait Speed (GS) (p = 0,001). Using the SARC-Calf, sarcopenia risk was 36.8 % and was associated with work activity (p = 0.029), socioeconomic status (p = 0.004), smoking (p = 0.009), disease status (p < 0.001), opportunistic infections (p = 0.015), CD4 T-cell count (p = 0.002), HGS (p = 0.001), Appendicular Skeletal Muscle Mass Index (ASMMI) (p = 0.009), and GS (p < 0.001). The agreement between tools was moderate (k = 0.49). Conclusion Sarcopenia risk, as determined by both tools, was higher in low-income PLHIV with opportunistic infections, CD4 T-cell count ≤ 200 cells/mm3, low HGS, and low GS, and lower in asymptomatic and non-smoking individuals. The authors recommend investigating these factors in hospital and outpatient settings. The SARC-Calf proved to be more appropriate for screening sarcopenia risk in PLHIV.

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Abstract Background Fibroadenomas are common benign breast lumps that can cause anxiety due to malignancy concerns, and Centchroman, a selective estrogen receptor modulator, has shown promise in reducing their size. This study aimed to evaluate the efficacy of Centchroman in reducing fibroadenoma size, mastalgia, anxiety, and depression in affected patients. Methodology A parallel-arm randomized controlled trial was conducted at a tertiary care Breast Clinic with 104 patients aged 18‒45 years having fibroadenomas ≤ 3 cm. Group A received Centchroman (30 mg on alternate days) and Group B received a placebo for 12 weeks. The primary outcome was fibroadenoma volume reduction measured by ultrasound, while secondary outcomes included reductions in mastalgia and improvements in anxiety and depression (HADS scores). Results Both groups showed fibroadenoma volume reduction over 12-weeks, with a greater reduction in the intervention group (3.67 ± 1.65 cm3 to 2.29 ± 1.04 cm3) than the control group (3.12 ± 1.16 cm3 to 2.73 ± 0.78 cm3), though the difference was not statistically significant (p = 0.342 and p = 0.781). However, 28.8 % of the intervention group experienced over 50 % volume reduction compared to 13.5 % in the control group (p = 0.007). Mastalgia significantly improved in the intervention group (VAS: 5.76 ± 2.13 to 2.24 ± 0.93, p = 0.023), with minimal improvement in controls. Anxiety and depression scores significantly decreased in the intervention group, with anxiety dropping from 9 to 5 and depression from 6 to 4 (p = 0.001). Conclusion Centchroman effectively reduces fibroadenoma size especially those with multiple fibroadenoma, mastalgia, and psychological distress in patients with fibroadenoma.

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Abstract Objective Acute Pulmonary Embolism (APE) is a disease with increasing incidence worldwide. Antithrombotics are the cornerstone of the treatment. Bleeding is an adverse event related to this therapy. The objective was to evaluate the prevalence of bleeding in a sample of Brazilian patients hospitalized with APE and the impact of this complication on mortality. Additionally, the performance of some bleeding predictive scores was evaluated in this sample. Methods A retrospective cohort study was carried out on patients hospitalized with APE from January 2009 through August 2017. The medical records of these patients were reviewed, and the bleeding recorded during hospital stay was classified according to the “Thrombolysis in Myocardial Infarction (TIMI) bleeding risk.” Five different predictive scores for bleeding after APE (RIETE, PE-SARD, VTE-BLEED, Kuijer, and ATRIA) were applied. Overall mortality at 30 days and one year were assessed. Results One hundred fifty-nine patients were included. The prevalence of any bleeding was 36/159 (23 %), major bleeding was 10/159 (06 %), minor bleeding was 11/159 (07 %), and bleeding requiring attention was 15/159 (10 %). Only major bleeding was associated with higher mortality at one-year follow-up with a Relative Risk (RR) of 2.00 (95 % CI 1.16-3.57; p = 0.044). All bleeding predictive scores evaluated showed low accuracy in identifying patients at higher risk of bleeding. Conclusion Patients hospitalized with APE in Brazil had a high prevalence of bleeding. The major bleeding increased the one-year mortality. The bleeding predictive scores assessed showed limited accuracy in identifying patients at high risk of bleeding.

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Abstract Background Sevoflurane (Sev) is an inhalational anesthetic for surgical procedures where it can trigger cognitive dysfunction and neuronal apoptosis. Gyosaponin (GpS) was studied for its effects on brain morphology and cognitive behaviors in Sev-anesthetized rats. Methods Male Sprague-Dawley rats were induced by 3 % Sev anesthesia, and 25 mg/kg and 100 mg/kg GpS were injected into the rats by tail vein. The in vitro model of Sev anesthesia was constructed by treating primary rat hippocampal neurons with 4.1 % Sev in the presence of GpS (5, 10, and 20 μM). The neuroprotective effects of GpS against Sev-induced cognitive deficits in rats were evaluated using the open field and Morris water maze tests. The apoptosis of hippocampal neurons was observed using HE staining and TUNEL assay. Apoptosis-related proteins and proteins related to the PI3K/Akt/mTOR pathway were determined via Western blot. Also, pro-inflammatory factors were measured via ELISA. Results GpS diminished the Sev-triggered apoptosis in neurons and Cleaved caspase-3, BAX, TNF-α, IL-6, lessened oxidative stress damage, and stimulated the PI3K/Akt/mTOR pathway. GpS therapy markedly enhanced learning and memory abilities in rats suffering from Sev-related cognitive impairments. Conclusion GpS ameliorates Sev-induced neurotoxicity and cognitive dysfunction by modulating the PI3K/Akt/mTOR pathway and alleviating neuronal apoptosis and oxidative stress.

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Highlights OSVE and multiple-choice tests can be used interchangeably in the context of formative assessment. OSVE and multiple-choice tests as effective tools to enhance intern training and monitoring. OSVE holds promise as a transformative tool, capable of ensuring the continuity and integrity of clinical skills assessment in medical education.

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Highlights We identified a distinctive pattern of serum metabolic signatures in juvenile idiopathic arthritis patients under methotrexate therapy. Methotrexate use is associated with a more efficient mitochondrial function. A decreased mitochondrial metabolism was observed in polyarticular and systemic JIA subtypes, with a decrease of several acylcarnitines’ concentrations.

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Highlights Renal Doppler marker variations within the initial 24 h in sepsis patients. RRI reduction after 24h of ICU treatment can be used for early detection of SA-AKI. Critical ultrasound for dynamic monitoring of renal perfusion.

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Highlights Incidence of frailty in elderly patients varies widely among different tools. FP and FS could be employed as tools for predicting frail conditions. Different tools had low consistency in predicting frail conditions.

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Highlights Question - Extension of the biliopancreatic loop increases l-cell activity after surgery bariatric? Findings - l-cell activity increased independent of extension of the biliopancreatic limb. Meaning - The additional beneficial effects of long BPL may be due to more rapid delivery of food and bile salts to more distal portions of the intestine.

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Highlights Guidelines recommended pulmonary rehabilitation in COPD. Self-driven pulmonary rehabilitation is an undertreatment for COPD patients in China. Chinese patients with COPD have worse clinical conditions. Treatment with pulmonary rehabilitation at institutes improves clinical outcomes. Chinese COPD patients are required to be treated as per proper guidelines.

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Highlights After cataract surgery, the prevalence rate of Descemet membrane Detachment was significantly higher in the group with keratome incisions (63.2 %) compared to that with femtolaser incisions (22.2 %).

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Highlights Restless legs syndrome is associated with lower information processing speed. Obstructive sleep apnea is not associated with lower information processing speed. Managing sleep disorders is critical for improving cognition in multiple sclerosis.

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Highlights Adverse effects of lenalidomide for Newly Diagnosed Multiple Myeloma (NDMM) cannot be ignored. Lower-dose PLD administered with dexamethasone and subcutaneous bortezomib is associated with a good durable response. Lenalidomide is retained as maintenance or salvage therapy if the DVD regimen fails.

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Highlight TRIB3 over-expression was related to the poor prognosis of LSCC. Patients with methylation related to high TRIB3 expression had a poorer prognosis. Knock-down of TRIB3 expression suppresses the growth, invasion and migration of LSCCs via PI3K- AKT- mTOR. TRIB3 may be viewed as a possible cancer biomarker.

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Highlights hsa_circ_0000105 modulates malignancy of NPC cells. hsa_circ_0000105 influences the malignant behavior of NPC via downstream miR-541-3p. hsa_circ_0000105 positively regulates S100A11 to accelerate the malignant behavior of NPC. hsa_circ_0000105 inhibits NPC tumor growth in vivo.

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Highlights Dry eye is more frequent in the urban than in the rural population. Dry eye is associated with dyslipidemia, visual display terminal, and ocular surface problems. Dry eye is more frequent in women and the associated factors are associated with antiallergics, chronic pelvic pain, and fibromyalgia. Dry eye in the elderly has distinct clinical associated factors.

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Highlights Stem cell therapy is a promising alternative in the spinal cord injury arsenal. Challenges in stem cell treatment in SCI: phase uncertainty and cell type controversy. Umbilical cord mononuclear cells may enhance recovery via multiple mechanisms. Umbilical cord mononuclear cells can promote histological improvement after SCI.

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Highlights Construction of a personalized risk prediction model for in-hospital mortality in patients with acute myocardial infarction undergoing Percutaneous Coronary Intervention (PCI). Identification of risk factors associated with in-hospital mortality in AMI patients who underwent PCI. Development of a nomogram prediction model for in-hospital mortality in AMI patients after emergency PCI. Evaluation of the nomogram model's effectiveness through c-index, internal validation, Hosmer-Lemeshow test, and calibration curve analysis.

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Highlights circLOC375190 reduction ameliorates neuronal autophagy and apoptosis in tMCAO mice. circLOC375190 knockdown improves OGD/R-mediated neuronal autophagy and apoptosis. circLOC375190 affects OGD/R-mediated neuronal apoptosis and autophagy by adsorbing miR-93-5p. circLOC375190 affects OGD/R-mediated neuronal apoptosis and autophagy by regulating the miR-93-5p/MKNK2 axis. circLOC375190 affects AIS autophagy by regulating the mTORC1/TFEB axis.

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Highlights Respiratory symptoms of PACS are associated with high serum Myl9 levels. Patients who have had COVID-19 can be divided into two groups according to their serum Myl9 levels. The neutrophil count is correlated with the Myl9 level at 6 months after infection.

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Highlights Correlation between pathologic complete response and endoluminal complete response. Half of pathologic complete responses do not achieve an endoluminal complete response. Gross findings do not perfectly reflect microscopic findings.

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Highlights NHANES data from 1999 to 2006 show a positive link between serum CRP levels and low muscle mass risk in US adults. An inverse J-shaped pattern emerges, indicating a non-linear association between CRP levels and low muscle mass risk, with critical points at 0.273 mg/dL for the overall population, 0.172 mg/dL for males, and 0.296 mg/dL for females. This nationally representative study underscores the crucial role of inflammation in muscle function and advocates for future research and clinical strategies to address inflammation's impact on muscle mass and function.

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Highlights ADSCs increased the viability (significantly less necrosis) of a TRAM flap in rats. Vessel formation in the ischemic segment of the flap was also enhanced by the ADSCs. Fluorescence microscopy indicated no differentiation of ADSCs into endothelial cells.

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Abstract Background and objective Colon Cancer (CC) is a common malignant tumor. The aim of this study was to investigate the role and regulatory mechanism of circular RNA pappalysin-1 (circ-PAPPA; hsa_circ_0088233) in CC. Methods In cancer tissues from CC patients, circ-PAPPA expression was measured and its relationship with patients’ clinical features was analyzed. Plasmid vectors or oligonucleotides interfering with the expression of circ-PAPPA, microRNA (miR)-656-3p or G-protein subunit Gamma-5 (GNG5) were transfected into CC cells. Cell viability was detected by MTT and colony formation assay; apoptosis was detected by flow cytometry; and cell migration and invasion were detected by wound healing assay and Transwell. Glycolytic capacity of CC cells was assessed by measuring glucose uptake and lactate production using commercial kits. The targeting relationship between miR-656-3p and circ-PAPPA or GNG5 was verified by bioinformatics website starBase and dual luciferase reporter gene assay assays. Results Circ-PAPPA was upregulated in CC and was negatively correlated with benign pathological features and 5-year survival rates of CC patients. Circ-PAPPA silencing inhibited the growth and glycolysis of CC cells through upregulating miR-656-3p. GNG5, a target of miR-656-3p, could reverse the impacts of silencing circ-PAPPA on CC cells. Conclusion Circ-PAPPA may play an oncogenic role in CC by promoting cell growth and glycolysis through the miR-656-3p/GNG5 axis.

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ABSTRACT Objective: This study investigated the predictive value of thrombin generation indices and Wells score in the development of Pulmonary Embolism (PE) in patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD). Methods: 160 patients who were admitted for AECOPD and underwent CT Pulmonary Arteriography (CTPA) were collected. Among them, a total of 62 cases were diagnosed with PE as the AECOPD with PE group, and the other 98 cases were not diagnosed with PE as the AECOPD group. The general data, past history and combined basic diseases, laboratory tests and other related clinical data of the two groups were compared, and the data collected were statistically analyzed to explore the diagnostic indexes that can predict PE in AECOPD. Results: History of venous thromboembolism, D-Dimer as well as Endogenous Thrombin Potential (ETP), Activated Partial Thromboplastin Time (APTT) coagulation indices, and Wells score was significantly higher in the AECOPD with PE group than in the AECOPD group, and Time to Peak (ttpeak), Albumin (ALB) and total protein were lower than those in the AECOPD group. The Wells score had a positive correlation with ETP and APTT and a negative correlation with ttpeak, which were all independent risk factors for PE in AECOPD. The Wells score had the best efficacy in predicting the occurrence of PE in patients with AECOPD with a cutoff value of 4.62. Conclusion: Significant correlations were found between the thrombin generation indices (ETP, APTT and ttpeak) and the Wells score, which can also be used for early diagnosis of PE in patients with AECOPD.

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ABSTRACT Objective: To assess the performance of pembrolizumab for the treatment of Gestational Trophoblastic Neoplasia (GTN). Methods: The Medical Subject Headings related to immunotherapy/pembrolizumab and GTN were used alone or in combination to retrieve relevant articles. The authors searched in EMBASE, MEDLINE/PubMed, Elsevier’s Scopus, and Web of Science until November/2024. The authors included any randomized controlled trials, cohort studies, case series, and case reports focusing on pembrolizumab treatment in GTN. Meta-analysis of proportions was carried out employing a random-effects model. The meta-analysis employed the inverse variance method, with the arcsine link function for the analysis of proportional data. All analyses were performed using Stata 18. For all analyses, a p-value < 0.05 indicated statistical significance. This study was registered on PROSPERO (CRD42023493329). Results: A total of 550 studies were identified after a literature search among which 15 original studies were included in the systematic review and in the meta-analysis. Pembrolizumab induced complete sustained remission in 71.59% (95% CI 53.27-84.78%; I2 = 0.00%, H2 = 1.00, p = 0.90) of cases. The subgroups metaanalysis showed pembrolizumab had similar performance, regardless of age (< 40 vs. ≥ 40-years-old, p = 0.38), GTN histopathology (Placental Site Trophoblastic Tumor [PSTT], Epithelioid Trophoblastic Tumor [ETT]/ noninvasive mole/others versus invasive mole/choriocarcinoma, p = 0.48), time from diagnosis to the beginning of immunotherapy (< 4 vs. ≥ 4-years, p = 0.84), pembrolizumab combined with chemotherapy (yes vs. no, p = 0.66). Conclusions: Pembrolizumab seems an effective treatment for patients with high-risk GTN with chemoresistant or relapsed disease, including cases of PSTT/ETT, notwithstanding patient age, time to initiate immunotherapy and whether or not it was associated with chemotherapy.

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ABSTRACT To analyze whether there is a significant difference in the virulence, symptoms, and outcomes of different Coronavirus Disease 2019 (COVID-19) variants in children under 2-years of age. We collected data from the Sistema de Informação de Vigilância Epidemiológica da Gripe, a nationwide Brazilian database on severe acute respiratory syndrome. The patients were classified according to four variants of concern: wild-type, gamma, delta, and omicron. The wild-type variant was defined as the baseline. A total of 11,153 patients were analyzed. The risk of presenting dyspnea (adjusted Odds Ratio[Aor = 1.20], 95 % Confidence Interval [95 % CI 1.07-1.34]) was higher in patients with gamma infection. Respiratory discomfort was more likely to be present for the omicron (Aor = 1.29, 95 % CI 1.15-1.43) and gamma (aOR = 1.26, 95 % CI 1.13-1.41) infections. Desaturation was more likely to be present for the omicron (aOR = 1.67, 95 % CI 1.50-1.86), gamma (aOR = 1.16, 95 % CI 1.43-1.79), and delta (aOR 1.41, CI 95 % 1.18-1.68) infections. Infection by the omicron variant was a protective factor for intubation (aOR = 0.78, 95 % CI 0.67-0.91) and death (aOR = 0.43, 95 % CI 0.35-0.53). Additionally, delta infection was a protective factor against death (aOR = 0.60, 95 % CI 0.43-0.85). The wildtype variant was responsible for most of the cases that evolved with death. Omicron appears to be responsible for milder symptoms than delta. Children between 1 and 6 months of age account for most cases, which is a concern because there is no vaccination coverage.

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ABSTRACT Objective: This study aimed to determine whether ultrasound measurements of the hands could predict treatment failure in treatment-naive women with early rheumatoid arthritis. Method: In a prospective case-control study, 48 women underwent blind assessments four times over 48-weeks, considering three failure stages: failure 1 (methotrexate), failure 2 (leflunomide), and failure 3 (adalimumab). Bilateral ultrasound exams evaluated wrist, 2nd, and 3rd Metacarpophalangeal Joints (MCPs), and Proximal Interphalangeal Joints (PIPs) for inflammatory indicators (synovial and tenosynovial proliferation using grayscale and Power Doppler [PD]) and joint damage (bone erosion and cartilage damage). Results: The study involved 48 women, aged 47.7 ± 11.6 years, with an average disease duration of 7.5 ± 3.5 months. Of these, 41 (85.41 %) experienced failure 1, 25 (52 %) experienced failure 2, and 5 (10.5%) experienced failure 3. Predictors for failure 1 included PD/Q10 total score > 2.5 (OR = 18.00), PD/SQ10 total score > 5.0 (OR = 23.2), PD/Q MCP score > 1.5 (OR = 14.58), and PD/SQ MCP score > 3.0 (OR = 35). For failure 2, predictors encompassed PD/Q10 total score > 4.5 (OR = 4.81), PD/SQ10 total score > 9.5 (OR = 4.81), PD/Q MCP score > 2.5 (OR = 4.92), PD/SQ MCP score >5.0 (OR = 6.22), and PD/Q PIP score > 1.5 (OR = 6.66). In relation to failure 3, a PD/Q wrist score > 2.5 (AUC = 0.79; p = 0.035) was indicative. Conclusions: Power Doppler proved to be a predictive indicator for treatment failure in early rheumatoid arthritis among treatment-naive women. It emerged as a predictor for both the initial and 2nd DMARD treatments, as well as the 1st immunobiological treatment, based on hand joint assessments. Trial registration: Clinical trials.gov NCT04752748.

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ABSTRACT Objective: The aim of this study was to evaluate monocyte subtypes and the chemokine receptors, comparing individuals with and without Chronic Venous Insufficiency (CVI). Method: The authors included patients undergoing surgery for varicose veins of the lower limbs (Classification of Venous Disorders - CEAP: C1-C3). Results: There were increased levels of classical and non-classical monocytes in the case group and a reduction in intermediate monocytes. Besides, there was higher expression of CCR5 in the non-classical monocytes and lower expression of CX3CR1 in the classical monocytes in the case group. Conclusions: The inflammatory process present in patients with CVI can modulate the monocyte phenotype and the expression of the chemokine receptors at the protein level.

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ABSTRACT The incorporation of long-acting reversible contraceptives (LARCs) into reproductive health strategies is crucial for enhancing access to effective contraception and reducing unplanned pregnancies (UPs). Evidence shows that even a modest shift from short-acting methods to LARCs can yield significant cost savings and improve health outcomes, both for individuals and public health systems. By facilitating single-visit placements and expanding the training of multidisciplinary teams, including nurses, healthcare providers can increase access to these effective contraceptive options.

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ABSTRACT In response to the high false positive rate of traditional Low-Dose Computed Tomography (LDCT) in diagnosing pulmonary malignant nodules, this study aimed to investigate the effectiveness of scoring of blood-based noninvasive biological metabolite detection combined with artificial intelligent scoring of non-invasive imaging in the clinical diagnosis of Pulmonary Nodules (PNs). In this retrospective study, risk scoring was performed in patients positive for pulmonary nodules and subsequently, PNs were sampled by invasive procedures for pathological examinations. The pathological classification was used as the gold standard, and statistical and machine learning methods showed, that in 210 patients (23 benign PN and 187 malignant PN), the risk score of Metabonomics, radiomics, and multi-omics had different levels of performance in different risk groups based on various predictive models. The Area Under the receiver operating Characteristic Curve (AUC) of the multi-omics model was 0.823. The present results indicate that a multi-omics model is more effective than a single model in the non-invasive diagnosis of pulmonary malignant nodules.

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ABSTRACT Objective: This study aims to analyze the risk factors for depression in peritoneal dialysis patients and to develop a predictive nomogram model for assessing these risks. Methods: A total of 326 peritoneal dialysis patients treated between August 2021 and December 2023 were selected as the training set. These patients were categorized into a non-depression group (229 cases) and a depression group (97 cases) based on the presence of depression. Additionally, 104 peritoneal dialysis patients from the same period were selected as the validation set. Clinical data were collected from all patients for analysis. Results: The depression group had higher proportions of female patients, non-employed individuals, those with a per capita monthly income of <2000-yuan, cardiovascular complications, cerebrovascular complications, and sleep disorders compared to the non-depression group. Additionally, the levels of hemoglobin and blood uric acid were lower in the depression group than in the non-depression group (p < 0.05). Gender, work status, per capita monthly income, cardiovascular complications, cerebrovascular complications, and sleep disorders are risk factors for depression in peritoneal dialysis patients (p < 0.05), while hemoglobin and blood uric acid are protective factors for depression in peritoneal dialysis patients (p < 0.05). Calibration curve analysis results showed that the predicted probability was basically consistent with the actual incidence rate. The results of the Decision Curve Analysis (DCA) demonstrated that the nomogram model developed in this study has strong clinical applicability. Conclusion: The nomogram model for predicting depression in peritoneal dialysis patients, which incorporates factors such as gender, work status, per capita monthly income, cardiovascular complications, cerebrovascular complications, sleep disorders, hemoglobin levels, and blood uric acid levels, demonstrates excellent calibration and discrimination. Additionally, it has high clinical applicability.

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ABSTRACT Objectives: The primary goal of this study is to evaluate the educational effects of medical students’ participation in a health expedition project. Specific objectives include assessing students’ perceptions of the educational value of the program, measuring gains in clinical knowledge and skills, evaluating behavioral changes, professional orientation, and students’ willingness to work within the public health system (SUS) after graduation. Methods: A quantitative methodology was employed, following Kirkpatrick’s four-level evaluation model. Questionnaires were administered before and after participation in the expedition to assess students’ reactions, learning, and empathy. The sample comprised all 15 students who participated in the expedition, with data analysis performed using R software. Results: The analysis highlighted that the expedition experience significantly impacted student’s career trajectories. Approximately 80 % of participants reported that the expedition positively influenced their career decisions, and 60 % expressed interest in working within the SUS. These findings suggest that while expeditions may not yield quantifiable gains in clinical competence in the short term, they can be catalysts in forming physicians oriented towards public service and social sensitivity. Conclusions: Health expeditions like the one conducted may not offer significant improvements in measurable clinical competencies in the short term but have a substantial effect on students’ career decisions, aligning with public health needs and reinforcing commitment to service in vulnerable contexts. This influence suggests that practical experiences in community settings play a crucial role in shaping medical students’ professional aspirations, emphasizing the importance of such programs in medical education aimed at social responsibility and health equity.

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ABSTRACT Introduction: The uterine leiomyoma is a pelvic solid tumor more frequent in women. The Magnetic Resonance-Guided Focused Ultrasound (MRgFUS) is a technique aimed at diminishing hypermenorrhagia and dysmenorrhea in symptomatic women. Objective: To show the effects subsequent to MRgFUS application on symptoms, quality of life, and myoma volume in symptomatic women. Methods: Fifty-two patients with symptomatic uterine myomas underwent MRgFUS followed by clinical evaluation, pelvis MRI, and administration of the UFS-QoL questionnaire at 6 months and 12 months to detect symptom improvements and decrease in myoma volume. Results: The mean myoma volume decreased 24 % after 6 months and 42 % after 12 months. The mean score on the UFS-QoL questionnaire increased 54 % after 6 months and 81 % after 12 months. There were no serious complications. Four patients had first-degree burns. No infection cases were reported. Two patients progressed to a myomectomy by surgical hysteroscopy and one of them underwent total hysterectomy 11 months after the MRgFUS treatment. Conclusion: This case series suggests that MRgFUS therapy is viable and effective in reducing symptoms and improving the life quality of symptomatic patients.

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ABSTRACT Objective: In the fight against Colorectal Cancer (CRC), chemotherapy resistance is a major obstacle. Therefore, it is imperative to identify effective biomarker therapeutics. Despite microRNAs (miRs) playing a crucial role in drug resistance, the mechanisms comprising miR-519d-3p’s role in CRC drug resistance have not been fully understood. Therefore, the present study aimed to investigate the biological function of miR-519d-3p in the chemosensitivity of CRC cells to 5-Fluorouracil (5-FU). Methods: CRC cells were treated with 5-FU and transfected. Cellular proliferation, invasion, and apoptosis were evaluated. The relationship between miR-519d-3p and 6-Phosphofructokinase-2/Frucose-2, 6-Biphosphatase-3 (PFKFB3) was analyzed, and their interaction in CRC was further investigated. In vivo tumor experiments were conducted to investigate the function of miR-519d-3p and 5-FU in CRC. Results: As determined, CRC cells overexpressing miR-519d-3p were more sensitive to 5-FU in vitro, as miR-519d-3p inhibits proliferation and invasion and stimulates apoptosis. miR-519d-3p directly targeted PFKFB3. In CRC cells, PFKFB3 overexpression rescued miR-519d-3p-induced 5-FU toxicity. In vivo results showed that mice co-treated with miR-519d-3p mimics and 5-FU showed higher antitumor activity. Conclusion: Overall, it may be possible to improve 5-FU chemosensitivity of CRC cells by targeting miR-519d-3p and PFKFB3.

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ABSTRACT Objective: To provide a protocol for the diagnosis and management of Acute Abnormal Uterine Bleeding (AUB) during menacme, addressing common causes, clinical evaluation, and treatment options. Methods: A review of current evidence and guidelines was performed to create a structured approach for healthcare professionals. Results: Acute AUB, defined as excessive uterine bleeding unrelated to pregnancy, requires immediate intervention. Causes vary by age and include coagulopathies, anovulation, and structural anomalies. Clinical stability, lab workups, and imaging are pivotal in guiding management. Initial treatment focuses on hemodynamic stabilization followed by medical therapies such as antifibrinolytics, hormonal agents, or surgical intervention when necessary. Conclusion: Early intervention in AUB ensures optimal outcomes, reduces complications, and allows transition to maintenance therapy to prevent recurrence.

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ABSTRACT Background: This study aimed to assess the predictive value of 7 routinely available inflammation biomarkers for stroke and all-cause mortality in 229 non-valvular AF patients. Methods and results: C-reactive protein, Albumin (ALB), d-dimer, fibrinogen, the number of platelets, lymphocytes, monocyte and neutrophils were measured. The Multivariable Cox proportional hazard model was used to assess the predictive value of the inflammation biomarkers for stroke and all-cause mortality, the c-statistic, Net Reclassification Improvement (NRI), and Integrated Discrimination Improvement (IDI) were calculated. Lymphocyte Monocyte Ratio (LMR) was the most informative biomarker for predicting stroke, and adding LMR to the CHA2DS2-VASc score did not improve its predictive ability for stroke, but it did improve its reclassification ability. Similar results were observed when comparing LMR+ CHA2DS2-VASc score with the ABC stroke score. For all-cause mortality, a Systemic Inflammation Score (SIS) score was calculated using ALB, fibrinogen and LMR, and adding SIS to the CHA2DS2-VASc score showed a significant improvement in its predictive ability and reclassification ability. There were no significant differences in predictive and reclassification ability for all-cause mortality between SIS+CHA2DS2-VASc score and ABC death score. Conclusions: Adding routinely available inflammatory biomarkers to the CHA2DS2-VASc score increased its ability to predict all-cause mortality, suggesting this cost-effective biomarker strategy may help to improve decision support in AF.

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ABSTRACT Background: Acute Obstructive Septic Cholangitis (AOSC) is a serious infectious disease of the biliary system. It is prone to develop into septic shock without prompt management. Methods: Bile was collected from 71 AOSC patients (45 AOSC without septic shock, 26 AOSC with septic shock) during biliary drainage and on days 1 and 3 postoperatively. The levels of High Mobility Group Protein 1 (HMGB1), Interleukin (IL)-1, IL-6, and Tumor Necrosis Factor alpha (TNF-α) were measured. The differences in the levels of biliary factors and their correlation with clinical biochemical indicators were assessed in the two groups. Results: HMGB1 gradually decreased in both groups in the postoperative period. Intraoperative levels of biliary HMGB1 were significantly higher in patients with AOSC with septic shock. TNF-α and HMGB1 decreased slowly in patients with AOSC with septic shock on postoperative days 1 and 3, and the levels of the factors decreased less. Biliary HMGB1 levels were negatively correlated with white blood cell count and positively correlated with blood urea nitrogen, blood creatinine, procalcitonin, and C-reactive protein. A bile HMGB1 level of 1108.3 pg/mL was the cut-off value to differentiate patients with AOSC with or without septic shock. Conclusion: Biliary HMGB1 levels are elevated in patients with AOSC with septic shock and decrease slowly in the postoperative period. This suggests that HMGB1 is of considerable importance as a potential therapeutic target in the pathogenesis of septic shock in AOSC patients.

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ABSTRACT Background: Uterine fibroids affect maternal and neonatal outcomes adversely. Pregnancy-Associated Plasma Protein-A (PAPP-A) and Uterine Artery Doppler (UAD) are used in the first and second trimesters to predict maternal and neonatal outcomes, including maternal preeclampsia, Small-for-Gestational-Age (SGA), and Low Birth Weight (LBW) babies. Methods: A retrospective review of medical records over 8-months was carried out for 60-patients who presented to the antenatal outpatient clinic. Inclusion criteria were the identification of fibroids in the first-trimester scan, PAPP-A blood test performed at the first visit, and UAD recorded at 20-weeks scan. Demographic characteristics, clinical parameters, pregnancy-related complications, and obstetric outcomes were extracted for data collection. Data analysis was performed to determine correlations between UAD parameters and PAPP-A levels and fibroid measurements for different fibroid types, and to determine the effect of fibroid presence on actual and estimated fibroid weight. Findings: Of 60 included patients, the mean age of patients was 35.8 ± 4.8 years, and each pregnant woman had an average of 2.9 ± 1.7 fibroids, with the majority (73 %) being large (> 5 cm). No complications, such as gestational hypertension, gestational diabetes, preeclampsia, abruption, and preterm birth were reported; only 6 (10 %) of women were sonographically diagnosed with SGA babies, while 2 (3.3 %) babies were LBW. UAD parameters and PAPP-A levels had no significant association with fibroid size (p > 0.05). Conclusion: There is a possible role of UAD and PAPP-A in determining pregnancy outcomes in the presence of fibroids, which needs to be explored by prospective studies.

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Abstract Objective Medical education is undergoing a profound transformation due to technological advancements. Integrating cutting-edge tools like virtual environments and computer-based simulators heralds a new era in teaching methodologies. The objective of the study is to analyze the performance and satisfaction levels of residents undergoing basic surgical skills training using virtual reality. Methods The authors recruited residents from the first year in general surgery and allocated them randomly into three groups: a) Text; b) Practice and c) Virtual reality. Initially, the residents completed a pretest for an evaluation and then they were trained according to the group they were assigned to. All the residents performed a 30-minute training session. After that, they took a posttest. Both tests were composed of multiple-choice ten questions. At the end of this study, the authors determined the score by calculating the delta of the performance (Δ = posttest -pretest). After the training, all the participants filled in a five-question satisfaction questionnaire. Results Regarding the difference between the pretest and post-test, there was no difference between groups. Only one participant (1/8) showed nausea in the virtual groups. The recommendation and satisfaction after the task were higher in the Virtual reality group compared to the Text group. There was an association between satisfaction after the exercises (VR) and recommendation score. Conclusions Virtual reality is safe and non-inferior to traditional surgical instrumentation training. This tool might be a practical and attractive alternative to the traditional instrumentation classes.

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Abstract Objective Isometric exercise can be an alternative approach to lowering blood pressure in individuals with hypertension. However, it is uncertain whether the muscle mass involved can influence Post-Exercise Hypotension (PEH). Thus, the authors evaluate the acute effect of an isometric exercise session with a Small Muscle Mass (SMM) and a Large Muscle Mass (LMM) on Systolic (SBP) and Diastolic (DBP) blood pressure in individuals with hypertension. Method Randomized clinical trial with 36 volunteers aged 40‒70y with hypertension allocated into (n = 12/group): control group (no exercise), SMM group (bilateral isometric handgrip contractions using a hydraulic handheld dynamometer), and LMM group (bilateral isometric full knee extension on a leg extension machine). Both exercise interventions consisted of 4 × 2 min of bilateral contraction at 30 % of the individual's maximum capacity. The authors used 24-hour Ambulatory Blood Pressure Monitoring (ABPM) after the interventions. One-way ANOVA or Generalized Estimation Equations (GEE) were used to test for potential differences (p < 0.05). Results The authors found no increase in SBP/DBP immediately after the interventions. However, 24 h ABPM revealed lower SBP post-intervention in the SMM group (Δ-4.1 mmHg; p = 0.044) and the LMM group (Δ-5.6 mmHg; p = 0.040) compared to the control group, with no difference between these groups. DBP did not change over a period of 24 h ABPM. Conclusions In conclusion, isometric exercise-induced PEH assessed by 24 h ABPM regardless of the muscle mass involved. This study shows that both interventions may contribute to lowering blood pressure in individuals with hypertension. Trial registration: www.clinicaltrials.gov; ID NCT03982758.

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Abstract Objective This study aimed to determine the normal range of fetal weight by ultrasound in pregnant women followed at the Obstetric Clinic of the Hospital das Clínicas of the Faculty of Medicine, University of São Paulo. Methods This retrospective cohort study included singleton pregnant women without associated maternal diseases, at 15-41 weeks of gestation, who underwent their last ultrasound up to 7 days before birth. Fetal parameters analyzed for the normal range were biparietal diameter, femur length, head and abdominal circumference. 3rd, 10th, 50th, 90th, and 97th weight percentiles were determined for each gestational age. Newborns were classified by birth weight as Small (SGA), Appropriate (AGA), or Large (LGA) for gestational age. Results Among 837 women admitted without maternal diseases, 136 were included and 379 examinations performed at 15-41 weeks of gestation. Multiple linear regression models were generated to develop the normal range of fetal weight. Three equations were selected, and six normal ranges were created considering the total population and stratified by fetal sex. Weight estimates were calculated for the 3rd, 10th, 50th, 90th, and 97th percentiles for each gestational age. Among the 136 newborns, 107 (78.7 %) were classified as AGA, 23 (16.9 %) as SGA, and 6 (4.4 %) as LGA. Conclusion The normal range of the fetal weight determined by ultrasound in this population showed a good correlation with gestational age, enabling the fetal weight gain pattern evaluation. The equation based on four parameters, including days before birth, presented the lowest percentage error variation to estimate the normal range.

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Abstract Objective To identify clinical and laboratory risk factors for Pulmonary Arterial Hypertension (PAH) in Idiopathic-Inflammatory-Myopathy (IIM) patients as well as construct a predicting model for PAH. Methods An IIM cohort in southeastern China was established, including 504 adult IIM patients who met the inclusion and exclusion criteria, and were hospitalized at four divisions of the First Affiliated Hospital, Zhejiang University School of Medicine (FAHZJU) from January 1st, 2018, to April 30st 2022. Serum cytokine profiles, myositis-specific antibodies as well as other factors of patients who met the inclusion and exclusion criteria were collected and analyzed. Results Of the 504 adult IIM patients, 25 IIM patients developed PAH and 48.0 % of them deceased within six months. IIM patients complicated with PAH were found to suffer from worse outcome (p < 0.001). After multivariate logistic regression analysis, age (p < 0.001), bacterial infection (p = 0.005), MYOACT score (p = 0.009), Interleukin (IL)-17A (p = 0.017), anti-SRP antibody (p = 0.011) and steroid monotherapy (p = 0.001) were identified as factors significantly associated with PAH in IIM patients. A “BAIMS” model was constructed by including the above six items to predict PAH with a cut-off value of ≥ 3 and an Area Under the Curve (AUC) of 0.877. Conclusion PAH is a rare but potentially fatal complication in IIM patients. Aging, complication of bacterial infection, elevated disease activity, increased serum IL-17A level, positivity of anti-SRP antibody and steroid monotherapy were significantly correlated with development of PAH in IIM patients. In addition, the BAIMS model was found valuable in prediction and early-identification of PAH in IIM patients.

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Abstract Background In transplantation, sex-mismatched procedures correlate with poorer outcomes. Previous research has indicated that females respond worst to Brain Death (BD) and that organ damage varies with the speed of BD induction. The authors aimed to investigate the effects of slow BD-induction on lung and kidney responses in male and female rats. Methods Males and female rats were subjected to slow induction of BD and kept for 4h. Blood gas samples were taken at 0 h and 4h. At 4 h, blood, urine and tissue samples were collected. IL-1β was measured in plasma, lung homogenate and lung culture. IL-6 was quantified in plasma, lung culture, and kidney homogenate. Leukocyte infiltration/activation was evaluated. Biochemical analyses of creatinine were performed in the plasma. Naïve animals were used as controls. Results Males presented reduced testosterone levels after 4h. Females presented reduced progesterone, whereas estradiol remained similar at 0 h and 4h. Compared with Naive, BD-groups presented increased plasma IL-1β and IL-6. Males and females presented reduced pO2 after BD, with females presenting even lower values at 4h. In lung tissue, males presented increased expression of IL-1β, whereas IL-1β was elevated in females in lung culture. Females presented increased cell infiltration/activation. In the kidney, males presented increased plasma creatinine, increased expression of caspase-3, and increased leukocyte migration to renal tissue than females. Conclusions The authors observed an organ and sex-dependent response to the slow-induction of BD. These results suggest that management strategies should consider the sex of the donor to achieve the best treatment, improving graft quality.

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Abstract Background Myocardial fibrosis contributes to LV mechanical dyssynchrony and fibroblast activation protein is considered as a specific biomarker related to tissue remodeling. The authors aimed to explore the relationship between LVMD and myocardial fibrosis, and patterns of LV fibrosis distribution in CAD and Degenerative Mitral Valve Regurgitant (DMVR) participants by the technique of 18F-AlF-FAPI PET/MR. Methods 37 CAD and DMVR participants with LVMD and normal ones underwent cardiac PET/MR imaging, the correlations between SUVmean of FAPI-uptakes and score/percentage of LV wall thickening, peak myocardial strains, and displacements were analyzed in PET/MR images, and ejection fractions and function parameters of mitral valve were compared. Results There was inverse correlation between SUVmean and score/percentage of LV wall thickening, peak circumferential and short-axial radial myocardial strains, and global peak myocardial strains and ejection fractions showed a decrease significantly in participants with heart diseases. In CAD participants, FAPI was distributed in the ischemic coronary arteries regions. Functions of myocardium in LAD and RCA regions were sensitive to fibrosis, however, those in LCX regions were resistant to fibrosis. In DMVR participants, high uptakes of FAPI were the locations of the valve annulus and papillary muscles, and SUVmean in the basal inferospetal/basal inferior segments were a positive correlation with function parameters of the mitral valve. Conclusion Uptake of 18F-AlF-FAPI in the myocardium could detect fibrosis and predict LVMD in CAD and DMVR participants. Moreover, there were different distributions of FAPI-uptake in those participants. In DMVR participants, SUVmean in the basal inferospetal/basal inferior segments could assess dysfunction of the mitral valve.

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Abstract Within the intricate tapestry of the global SARS-CoV-2 pandemic, this study delves into the intricate interplay of clinical data to elucidate prognostic factors associated with complications in patients concomitantly afflicted with hematological disorders and SARS-CoV-2. An exhaustive analysis of 71 individuals, spanning the period from November 2022 to March 2023, aims to unveil distinctive clinical characteristics and explicate the nuanced determinants steering the trajectory of the disease. The updated findings reveal a multi-faceted correlation, underscoring the complex interplay of clinical parameters. Among individuals with hematological disorders, anomalously elevated ferritin levels are closely associated with the development of SARS-CoV-2 pneumonia, while interferon-γ is intricately linked to the severity of SARS-CoV-2. Conversely, elevated ferritin levels, increased D-dimer and fibrin degradation products, along with significantly elevated iron levels, manifest a significant association with patient mortality. Intriguingly, those in patients in complete hematologic remission confront an augmented risk of developing SARS-CoV-2 pneumonia, while those abstaining from anti-tumor treatments exhibit mitigated case severity. This study unveils the intricate interplay of clinical factors impacting the prognosis of SARS-CoV-2 complications in individuals with hematological disorders. The cognizance of aberrant interferon-γ activation and nuanced associations with ferritin, iron levels, and coagulation markers contributes to a more holistic comprehension of the prognostic landscape.

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Abstract Introduction Renal Ischemia-Reperfusion Injury (RIRI) often arises due to heightened oxidative stress, rendering it a central focus of research. Sestrin2 plays a pivotal role in regulating oxidative stress; nevertheless, its impact on the renoprotective properties of Eugenol (EU) during RIRI warrants further investigation. Methods Mice and TCMK-1 cells were categorically assigned into six groups: Sham/Control, Ischemia-Reperfusion (IR)/HR (Hypoxia-Reoxygenation), IR/HR+EU, Sham/Control+Sestrin2-KO, IR/HR+Sestrin2-KO, and IR/HR+EU+Sestrin2-KO. The effects of EU and the involvement of Sestrin2 in RIRI/HR were evaluated using Urea Nitrogen (BUN), Creatinine (Scr), Superoxide Dismutase (SOD), Glutathione (GSH), Catalase (CAT), and Malondialdehyde (MDA) assay kits; western blotting; cell viability assays; HE-staining; and Reactive Oxygen Species (ROS) detection. Results Following RIRI/HR, a marked deterioration in kidney function and a significant surge in oxidative stress levels were observed. However, EU treatment ameliorated renal injury and inhibited oxidative stress. Additionally, EU upregulated Sestrin2 expression, and the renoprotective effects of EU were reversed upon Sestrin2 knockdown. Conclusion The present study posits that EU effectively mitigates RIRI/HRI (Hypoxia-Reoxygenation Injury), and its mechanism of renal protection potentially involves the upregulation of Sestrin2, coupled with the inhibition of oxidative and Endoplasmic Reticulum Stress (ERS).

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Abstract Background A 2 mm-thick dermal allograft and autologous Long Head of the Biceps Tendon (LHBT) Superior Capsule Reconstruction (SCR) could provide improved clinical and radiographic outcomes for posterosuperior Massive Irreparable Rotator Cuff Tears (MIRCTs). Methods A retrospective study was conducted between April 2019 and October 2021. The LHBT was rerouted 5 mm posteriorly to the bicipital groove, and a 2 mm-thcick dermal allograft was used to cover the rerouted LHBT. Clinical assessment included Constant-Murley Shoulder score (CMS), American Shoulder and Elbow Surgeons (ASES) score, Subjective Shoulder Value (SSV), Visual Analog Scale (VAS) pain scores, and active ROM measurements. The radiological assessment included Acromiohumeral Distance (AHD), Superior Capsular Distance (SCD), muscle Fatty Infiltration (FI), and follow-up SCR integrity using ultrasound two years after surgery. Results 25 patients (7 male, 18 female) were included with a mean age of 64.2 ± 6.9 years. Active ROM, AHD, and SCD did not change significantly after the surgery. Patients' VAS (8.3 ± 0.7 to 1.3 ± 0.6, p < 0.001), SSV (22.4 ± 8.6 to 77.6 ± 12.7, p < 0.001), CMS (36.2 ± 6.8 to 79.9 ± 8.4, p < 0.001), and ASES (37.2 ± 10.0 to 80.5 ± 5.7, p < 0.001) improved significantly at final follow-up. The ultrasound examination of all patients demonstrated a healed dermal allograft on the supraspinatus footprint. One patient (4 %) had a postoperative trauma causing irreparable subscapularis tear, leading to reverse total shoulder arthroplasty during revision surgery. Conclusions The combined SCR technique using a 2 mm dermal allograft and autologous LHBT for posterosuperior MIRCTs significantly improved the patient-reported outcomes.

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Abstract Objective To explore the role of hsa_circ_0095812 (circLRRC4C) in periodontitis and its mechanism with miR-485-3p and Thrombospondin-1 (THBS1). Methods Periodontal tissues were collected from periodontitis patients. Periodontal Ligament Cells (PDLCs) were stimulated with Lipopolysaccharide (LPS) and transfected. Cell viability, inflammation, apoptosis, and pyroptosis were analyzed. A mouse model of periodontitis was constructed and injected with a lentiviral plasmid vector targeting circLRRC4C. Immunohistochemistry was performed on the periodontal tissue of model mice. The relevant expression level of genes was measured via real-time reverse transcriptase-polymerase chain reaction or Western blot. The relationship between circLRRC4C and THBS1 with miR-485-3p was analyzed. Results CircLRRC4C was highly expressed in periodontitis tissues of patients and LPS-treated PDLCs. Downregulating circLRRC4C attenuated LPS-induced PDLC inflammation, apoptosis and pyroptosis and recovered cellular viability. CircLRRC4C acted as a sponge for miR-485-3p. CircLRRC4C affected LPS-induced PDLC apoptosis, pyroptosis and inflammation by regulating miR-485-3p. THBS1 was the target gene of miR-485-3p. Inhibition of THBS1 effectively improved LPS-induced periodontitis. CircLRRC4C aggravated LPS-induced PDLC apoptosis, pyroptosis and inflammation by regulating the miR-485-3p/THBS1 axis. Suppressing circLRRC4C effectively improved periodontitis in mice. Conclusion CircLRRC4C induces periodontitis progression by adsorbing miR-485-3p-mediated THBS1 expression.

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Abstract Objective p53 is a key tumor suppressor, aCnd loss of p53 function promotes the progression of many cancers. Helicobacter Pylori (HP) is mainly involved in the progression of gastric carcinoma, but its role in Oral Squamous Cell Carcinoma (OSCC) is controversial. The primary objectives of this study were to investigate the expression levels of p53 in OSCC tissues and to examine the serum levels of CagA in OSCC patients. Additionally, the authors aimed to explore the potential association between p53 expression and CagA levels in OSCC. Method A total of 65 patients diagnosed with OSCC and 42 healthy volunteers were recruited in this study. The clinical pathological parameters of all patients were collected. Reverse transcription-quantitative polymerase chain reaction was performed to detect the expression of p53 in tissues. Receiver Operating Characteristics Curve (ROC) analysis was used to assess the sensitivity of p53 for the diagnosis of OSCC. The concentration of Cytotoxin-Associated gene A (CagA) in serum was assessed by enzyme-linked immuno sorbent assay. Results The results indicated that the p53 expression in oral mucosal tissues was downregulated while the concentration of CagA in serum was increased in OSCC patients. Besides, p53 expression was correlated with tumor stage. OSCC patients showed a higher HP positive rate than in healthy people. Conclusions In conclusion, this study demonstrated that decreased p53 expression and elevated serum CagA levels might be correlated with OSCC progression and diagnosis.

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Abstract Introduction Leukoreduction is performed to decrease the occurrence of adverse effects of transfusion, and can be performed by pre-storage (bench or in-line) or post-storage filtration (bedside) moment. The authors verified the effect of the leukoreduction filtration moment of Red Blood Cell (RBC) and Platelet Concentrate (PC) on the occurrence of Adverse Transfusion Reactions (ATRs), the presence of Healthcare-Associated Infections (HAIs), Length of Hospital Stay (LOS), and hospital death. Methods Retrospective cohort conducted at the Hospital das Clínicas of the Medicine Faculty of the University of São Paulo, and at the Fundação Pró-Sangue Hemocentro in São Paulo, Brazil. Adult patients, hospitalized for >24 hours, who received leukoreduced RBC and/or PC transfusion between 2017‒2020 were included. The generalized mixed effects model and the Wald test were applied in the analysis with a significance level of 5 %. Results The authors evaluated 3668 patients who received 23,782 transfusions and we found no evidence of a leukoreduction filtration moment effect for ATR (p = 0.991) or HAI (p = 0.982), regardless of the transfused blood component. Meanwhile, the leukoreduction filtration moment had an effect (p < 0.001) on LOS, depending on the blood component transfused (p = 0.023), with pre-storage RBC filtration showing better performance, while in-line filtration stood out for PC. Both the leukoreduction filtration moment and the blood component (p = 0.041) influenced hospital death, with emphasis on the protective effect of bench RBC filtration and pre-storage PC filtration. Conclusion The leukoreduction filtration moment associated with the blood component had an effect on the LOS and hospital death of patients undergoing transfusion.

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ABSTRACT Introduction Retinoblastoma-Binding Protein 4 (RBBP4), belonging to the WD-40 family, is an important member of the Polycomb Repressor Complex 2 (PRC2), the Nucleosome Remodeling and Deacetylation complex (NuRD), and is involved in chromatin remodeling, histone deacetylation, and H3K27 methylation. Methods The effects of cisplatin treatment on cell viability were evaluated using the MTT assay. Western blotting was employed to analyze protein expression, and RNA interference-mediated knockdown of RBBP4 and cyclin D1 was conducted using Lipofectamine 2000. The formation of colonies was evaluated following a 14-day cisplatin treatment period. Cisplatin uptake was quantified by atomic absorption spectrophotometry. RNA sequencing was conducted on total RNA extracted from cells, and lentiviral vectors were employed for gene overexpression, followed by puromycin selection. Immunohistochemistry was performed on tissue microarrays of lung and cervical adenocarcinoma in order to evaluate RBBP4 expression. Results In this study, cisplatin was found to induce RBBP4 expression in human lung cancer A549 cells, and RBBP4 expression in cisplatin-resistant A549/DDP cells was significantly higher than in A549 cells. Downregulating RBBP4 expression by small interfering RNA significantly increased the sensitivity of A549 and A549/DDP cells to cisplatin. Conversely, lentiviral-mediated RBBP4 overexpression reduced sensitivity to cisplatin. Mechanistic studies showed that downregulated RBBP4 increased cell sensitivity to cisplatin mainly by inhibiting cyclinD1 expression, and lentiviral-mediated cyclinD1 caused the opposite effects. These same results were verified in human HeLa cells and in cisplatin-resistant HeLa/DDP cells. Discussion This study showed that RBBP4 regulates the sensitivity of tumor cells to cisplatin and is a potential target for reversing cisplatin resistance in tumor cells.

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Abstract Objective To provide an overview of the activities and impact of an Evidence-Based Care Program (EBCP) on professionals’ decision-making in a large hospital located in São Paulo, Brazil. Methods Retrospective descriptive analysis of a hospital EBCP's database (covering a 40-month period), involving data from the studies conducted and an online feedback survey. Results Since its inception, the EBCP performed 95 scientific technical reports, including 55 Rapid Systematic Reviews (RSR) and 40 Literature Reviews (LR). The authors identified 21 review topics, with the 3 most common being inpatients (n = 20), oncology (n = 11), and surgical procedure (n = 9). The 3 most common technologies assessed were medical devices (n = 28), drugs (n = 27), and scale/questionnaire (n = 16). Studies were mainly used to update policy or procedure (n = 59), support scientific research (n = 10), support clinical program development (n = 8), provide clinical guidance (n = 7), or as a communication tool (n = 5). Among the requestors who responded to the feedback survey (76/95), 97 % agreed or strongly agreed that they were satisfied with the review delivered, and 100 % indicated that they likely would request a review in the future and would indicate the EBCP to a coworker. Among the RSR responders (51/55), 94 % agreed or strongly agreed that the EBCP work informed their project or final decision, and 32 % reported that the result presented changed their perspective about the technology assessed. Conclusion Employing evidence-based methodology, the program provided timely and pertinent evidence for local decision-making. Health professionals who utilized the EBPC expressed high satisfaction with the process and reported a positive shift in their decision-making.

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Abstract Background Gastric Cancer (GC) remains a leading global cause of cancer mortality, underscoring the urgent need for advanced prognostic tools. This study aimed to construct and evaluate a prognostic risk signature based on Supramolecular Polymer-Related Genes (SPRGs) in gastric cancer. Methods The authors downloaded data from TCGA-STAD, GEO, and CCLE databases for patients with GC and validation cohorts. Through consensus clustering, Cox proportional hazards models, LASSO Cox regression, and nomogram development, the authors identified and constructed a GC Prognostic risk Index (SPI). Additionally, the authors conducted drug sensitivity analysis and immune landscape assessment. Functional evaluations were conducted through colony formation, transwell invasion, and wound healing assays. Results The authors identified that 182 SPRGs were significantly upregulated and 226 were downregulated in gastric cancer. Consensus clustering revealed two molecular subtypes, with cluster 1 having significantly lower overall survival compared to cluster 2. SPI effectively distinguished high-risk and low-risk patients across all cohorts. Furthermore, SPI was associated with tumor stage, lymph node metastasis, and tumor size, and could predict drug sensitivity in GC patients. Immune landscape analysis showed higher infiltration of naïve B cells, M2 macrophages, and activated NK cells in high-SPI patients. A nomogram model for GC prognosis using SPI and patient age was developed. KLC1 knockdown significantly suppressed GC cell proliferation, while markedly attenuating metastatic potential and invasion capacity. Conclusion This study constructed a prognostic risk signature based on SPRGs in gastric cancer, which is closely related to clinical pathological features, drug sensitivity, and immune landscape, providing new insights for personalized treatment.

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Abstract Introduction Brugada Syndrome (BrS) typically manifests with a dynamic type 1 Brugada pattern (Br1ECGp) that depends on the dominance of the sympathetic or parasympathetic nervous system. This pattern is more prominent during activities that stimulate the vagus nerve, such as sleeping and after meals. By conducting the tilt table test and adding high precordial leads to the standard protocol, it is possible to provoke sympathetic or parasympathetic responses, providing valuable information. Materials and methods This was an observational, cross-sectional and hypothesis-generating pilot study. The tilt table test was performed with high precordial leads on three Brugada patients to assess the Br1ECGp during the test. The ECG features were continuously recorded to analyze variations during all phases of the test. Results The first patient exhibited a significant Br1ECGp that disappeared during the upward phase of the tilt table test and reappeared during the recovery phase. The second patient had a Br1ECGp in three leads that persisted during both the upward and recovery phases of the tilt table test. The third patient displayed a Br1ECGp in three leads, which was maintained during the upward phase in two leads and recovered during the recovery phase. The third patient was the only one to experience cardioinhibitory syncope. Conclusion This study provided insights into the dynamics of the Br1ECGp during the tilt table test when enhanced by high precordial leads. It reaffirmed that the Brugada ECG pattern is influenced by sympathetic or parasympathetic dominance.

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Abstract Background To investigate the combined effect of transperineal ultrasound and Shear Wave Elastography (SWE) in the evaluation and monitoring of pelvic floor functions after total hysterectomy. Methods Fifty-two women who planned to undergo total hysterectomy from January 2019 to December 2022 in Nantong Third People's Hospital were selected, and the pelvic floor functions were assessed using transperineal ultrasound combined with SWE. The dynamic alterations in pelvic floor functions at different time points were compared after hysterectomy. The differences in pelvic floor parameters were compared between Transabdominal Total Hysterectomy (TAH) and Laparoscopic Total Hysterectomy (LTH). Results The Posterior Urethravesical Angle at rest and Valsalve maneuver (R-PUA, V-PUA), antero-posterior diameter of the hiatus at rest and Valsalve maneuver (R-HAPD, V-HAPD), and elastic modulus of left and right puborectalis at rest (R-L-PRE, R-R-PRE), the Urethral Rotation Angle (URA)were obviously higher at 3 mon after surgery than before surgery and at 1-mon after surgery; the bladder neck-symphyseal distance at rest and Valsalve maneuver (R-BSD,V-BSD), and the difference in elasticity between the left and right puborectalis muscles (L-∆E, R-∆E) were markedly lower at 3 mon than before surgery and at 1 mon after surgery; V-BSD, L-∆E, R-∆E were obviously decreased and the Bladder Neck Descen (BND), URA, V-PUA were obviously increased in the TAH group in comparison with the LTH group. Conclusion Pelvic floor functions start to be weak at 3 months after total hysterectomy. TAH causes more significant damage to the structures and functions of the pelvic floor.

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Abstract Background Laryngeal Squamous Cell Carcinoma (LSCC) may be treated clinically or surgically as a therapeutic option with a curative intention. The aim of this study is to compare direct medical costs and overall survival associated with the treatment of LSCC. Methods Retrospective cost-consequence analysis, from the perspective of a Brazilian public hospital that included patients with LSCC, from 2014 to 2017. Unit costs were estimated using a macro-costing approach. The Propensity Score Matching method was used. Survival analyses were performed using the Kaplan-Meier method. Results The therapeutic modalities were similar in terms of total costs: USD 32,259.65 for the clinical group and USD 34,385.87 for the surgical group (p = 0.215). Patients in the surgical group showed better overall survival than the clinical group (HR 0.53; p = 0.047). Conclusion Both therapeutic modalities for the treatment of LSCC showed similar total costs. Nevertheless, overall survival was better in the surgical group.

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Abstract Objective The COVID-19 pandemic has a significant impact on the physical and mental health of people around the world. Parkinson's patients need to visit hospitals regularly to evaluate and adjust the dosage of drugs. Studies have shown that anxiety, exacerbated by existing conditions ‒ including the challenges posed by the COVID-19 pandemic ‒ can aggravate the symptoms of Parkinson's disease. This study aims to assess the impact of the quarantine period on the severity of movement symptoms, quality of life, non-motor symptoms, and the relationship with sex, education level, and age in patients with Parkinson's disease. Methods This descriptive cross-sectional study includes 200 patients with Parkinson's disease who were treated in Bu Ali Hospital from April 2019 to the end of 2021. Primary data was collected using the patients' files, which included information on age, gender, education level, medications and dosage, duration of Parkinson's disease, the severity of the disease was evaluated based on the Hohen and Yehr (H&Y) criteria, and Quality of Life (QOL) and the impact of the quarantine period on their illness and quality of life has been collected through the Parkinson's Disease Questionnaire (PDQ-39) questionnaire. The collected data were analyzed using SPSS software, descriptive statistics, t-test, and analysis of variance. Results The quarantine period has a significant effect on the severity of Parkinson's disease and quality of life. The mean severity of the disease increased from 2.85 before quarantine to 3.30 during quarantine (p < 0.05), indicating an increase in motor symptoms. Similarly, quality of life scores in all dimensions decreased from 62.8 before quarantine to 48.2 during quarantine (p < 0.05), indicating a decrease in quality of life. Pearson's correlation test was used to investigate the relationship between age and the change in patients’ quality of life and the change in disease severity (p < 0.05). Conclusion The quarantine period due to the COVID-19 epidemic has had a significant impact on the severity of Parkinson's disease and the quality of life of patients. The findings of this study indicate the need to develop strategies to provide better health care, social support, and physical activity for patients with Parkinson's disease during quarantine and the pandemic.

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Abstract Objective To verify the effect of 12 weeks of Combined Training (CT) in patients suffering from COVID-19 of mild to moderate intensity. Methods 69 participants diagnosed with mild to moderate COVID-19 were evaluated, with shortness of breath as the main symptom. All of them were sent by the Centro de Atendimento ao Funcionário do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (CEAC-HCFMUSP). The sample was divided into three groups: Group 1 (G1) - 26 patients diagnosed with COVID-19 evaluated before and after combined training together with nutritional guidance. Group 2 (G2) - 21 patients diagnosed with COVID-19 were evaluated before and after 12 weeks. Patients in G2 (control) did not participate in the protocol but were instructed to train outside the hospital and did not receive nutritional guidance. Group 3 (G3) - 22 patients diagnosed with COVID-19 were evaluated before and after combined training along with nutritional monitoring and post-workout whey protein supplementation throughout the duration of the protocol. Results The three groups did not have significant statistical differences when compared to each other, but there was significant intragroup improvement in the analyzed variables. There was an improvement in cardiorespiratory, metabolic, and muscular fitness. Furthermore, late symptoms of the disease were reduced at the end of the program. Conclusion The results of the dependent variables analyzed were significant within groups, CT was an efficient training model in improving the patient's general condition (fatigue and dyspnea) when training was controlled with supervision.

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abstract Objectives Using the Triglyceride-Glucose (TyG) index to categorize patients and to compare the effects of different oils on metabolic biomarkers among diabetic patients. Methods A total of 98 diabetic patients were included in this retrospective hospital-based study of which data were obtained from medical and dietary records. The participants were divided into soybean oil groups or olive oil groups according to the dietary packages they chose during hospitalization, which merely differed in the kinds of cooking oil (olive oil vs. soybean oil). After being matched based on propensity scores in a 1:1 ratio with a 0.2 caliber width, 70 subjects were finally included in the analysis. Results Compared to admission, blood pressure, lipids, and postprandial blood glucose were decreased at discharge in both groups. Grip strength levels of both hands increased in the olive oil group, while no statistical differences were found for these measures in the soybean oil group. In both the soybean oil and olive oil groups, metabolic biomarkers showed broader improvements at discharge for participants with high TyG levels compared to those with low TyG levels. Additionally, patients with high TyG levels in the olive oil group experienced the greatest benefits in terms of blood glucose, lipids, blood pressure, and handgrip strength before and after hospitalization. Conclusions Olive oil may have more advantages in improving metabolic risk factors among diabetic patients. The TyG index can be a valuable tool for clinically screening and categorizing patients for personalized precision treatment.

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Abstract Objective This study aimed to evaluate the success and complication rates of the Susanna UF Glaucoma Drainage Device (SUFGDD) in treating refractory primary congenital glaucoma. Patients and methods In this prospective non-comparative clinical trial, patients with refractory primary congenital glaucoma, under 18-years-old, who had unsuccessful prior glaucoma surgeries, underwent standardized SUFGDD implant surgery. All procedures were performed by a single surgeon (A.D.P.R.). Pre and postoperative intraocular pressure (IOP), number of antiglaucoma eye drops, surgical complications, and any subsequent related events were recorded. Success criteria were defined as follows: (I) IOP ≥ 5 and ≤ 21 mmHg; (II) IOP ≥ 5 and ≤ 18 mmHg. Each group was further categorized as absolute success (without medication) or qualified success (including those with medication). Results The study included 45 eyes from 31 patients, with an average age of 6.14 ± 5.02 years (range: 9 months‒18 years). The mean follow-up time was 37.78 ± 10.44 months. Mean IOP decreased from 28.18 ± 5.69 mmHg to 14.73 ± 2.90 mmHg (p < 0.05). The average number of antiglaucoma medications was reduced from 2.96 ± 0.74 to 1.40 ± 1.23 (p < 0.05). At 36-months postoperatively, the qualified success rates for criteria I and II were 93.3 % and 77.8 %, respectively. Seven eyes (15.6 %) experienced complications, all of which required reoperation; six cases were successfully managed, while one case resulted in permanent vision loss due to endophthalmitis. There were no significant associations between complications and analyzed risk factors (e.g., number of previous surgeries, age at surgery, past glaucoma surgeries, preoperative IOP, and number of preoperative eye drops). However, an association was observed between the occurrence of complications and surgical failure in the qualified success group for criterion II (HR = 6.50; 95 % CI 1.20‒31.35; p = 0.029). Conclusion In this studied cohort, SUFGDD achieved qualified success rates of 93.3 % and 77.8 %, for criteria I and II, respectively, at 36-months, with a complication rate of 15.6 %.

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Abstract Objective The study explored the molecular mechanism of circNOLC1 influencing Testicular Germ Cell Tumor (TGCT) progression. Methods The study used TGCT tissue samples and cell lines for investigations. The circNOLC1 and miR-140-5p expression in TGCT tissues were done through RT-qPCR. Analysis of the association of circNOLC1 with TGCT clinic-pathological features was also done. Transfections of circNOLC1, miR-140-5p or Insulin-like GrowthFfactor 1 Receptor (IGF1R)-related sequences or plasmids into TCAM-2 and NCCIT TGCT cells were done. The circNOLC1, miR-140-5p, and IGF1R mRNA expression in cells were done through RT-qPCR. Interaction between miR-140-5p, circNOLC1, and IGF1R was examined using a dual-luciferase reporter assay. MTT assay and colony-forming assay were used to investigate cell proliferation. Apoptosis was determined by flow cytometry. Transwell assay was used to investigate cell invasion. IGF1R protein expression was determined through a western blot. Results Increased circNOLC1 in TGCT tissues was correlated with lymph node metastasis, clinical stage, and pathological grade of TGCT patients. CircNOLC1 knock-down inhibited TGCT cell proliferation, colony formation, and invasion, and promotedapoptosis. MiR-140-5p was reduced while IGF1R was upregulated in TGCT tissues and cell lines. Moreover, miR-140-5p mimic could reverse the effect of circNOLC1 knock-down on malignant behaviors of TGCT cells. The authors demonstrated that elevated IGF1R reversed the negative effect of miR-140-5p mimic on TGCT cell proliferation, colony formation, and invasion. CircNOLC1 can act as a sponge of miR-140-5p to up-regulate the IGF1R expression level. Conclusion The study highlights that circNOLC1 promotes the progression of TGCT by regulating the miR-140-5p/IGF1R axis.

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Abstract Introduction The imbalance between the demand for liver transplants and the shortage of donors can be addressed by expanding the donor pool, including using extended criteria donors. This strategy may reduce waiting time and list mortality but can increase poor graft function rates, affecting short-term outcomes. Tools to predict and diagnose Early Allograft Dysfunction (EAD) are crucial. Elastography for Liver Stiffness Measurement (LSM) may predict EAD and graft loss early post-transplant. Methods In this prospective observational study, the authors assessed the diagnostic accuracy of elastography for predicting EAD or loss in liver transplant recipients admitted to the ICU of Hospital das Clínicas, Universidade de São Paulo, from 2016 to 2018. Patients underwent daily LSM from ICU admission to day 7 post-transplant. EAD was defined by Olthoff et al.'s criteria, and allograft loss was defined by the need for retransplantation or death within 180 days. Results EAD developed in 27 patients (44.3 %). The median LSM was 2.12 m/s (IQR 1.87-2.67 m/s) for the EAD group and 1.70 m/s (IQR 1.55-1.90 m/s) for the non-EAD group. For predicting EAD, elastography on day 1 had a c-statistic of 0.83, sensitivity 41 %, specificity 97 %, and accuracy 83 % at a cutoff of 2.39 m/s. For predicting early allograft loss, the c-statistic was 0.93, with a sensitivity 76 %, specificity 100 %, and accuracy 93 % at a cutoff of 2.25 m/s on day 1. Conclusion Elastography demonstrated robust performance in predicting EAD and early graft loss post-transplant, outperforming traditional prognostic scores. Further multicenter studies are needed to confirm these findings.

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Abstract SARS-CoV-2 presents a hyperinflammatory scenario due to systemic inflammatory response syndrome with intense cytokine release, with consequent extrapulmonary involvement in 20 % of patients. The authors studied whether COVID-19 intestinal damage is a direct action of the virus on intestinal epithelial cells, with damage mainly at the tight junction. This is a retrospective observational study in a tertiary hospital emergency department. The authors studied 87 patients (46 patients over 61 years and 41 patients under 60 years old) with severe SARS-CoV-2 infection. The authors measured two plasma markers, LPS-Binding Protein (LBP) and ileal Fatty Acid-Binding Protein (iFABP). Furthermore, the authors evaluated the interaction between the two markers. TNF-α and IL-1 β were higher in bacterial co-infected patients and TNF-α was also higher in the older patients. Plasma iFABP levels were not statistically different in patients with bacterial co-infection; however, higher levels were found in the older population. Plasma LBP levels were higher in patients with bacterial co-infection when compared to patients without infection; however, when comparing plasma LBP levels in the older population with younger patients, no differences could be found. LBP, FABP, and cytokines can discriminate between bacterially infected patients and also discriminate elderly patients. The present study suggests that intestinal barrier dysfunction in SARS-CoV-2 infections is mainly due to damage to the intestinal tight junction complex with a disproportionately lower damage to enterocyte. In the older population, the authors also observed an increase in intestinal epithelial damage.

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Abstract Aim Chronic Hepatitis-C Virus (HCV) treatment has evolved significantly in recent years with Direct-Acting Antivirals (DAAs). The traditional care cascade includes several steps that limit its impact, and simplification protocols have emerged. Therefore, the authors explore a simplified treatment strategy for HCV in a healthcare system with limited access to specialized care. Subject and methods Chronic HCV, DAA-naïve patients waiting for in-person specialized care were invited to a single-arm non-inferiority trial to evaluate a simplified treatment protocol with a single face-to-face appointment and minimal monitoring of antiviral therapy. The unique visit consisted of an HCV presentation followed by individual medical consultation, blood tests, and delivery of sofosbuvir-velpatasvir pills for a 12-week treatment. Patients were remotely monitored without scheduled on-treatment appointments or phone calls. After treatment, teleconsultation using video was offered. The primary outcome was Sustained Virological Response (SVR) 12-weeks post-treatment. It was analyzed with Intention-To-Treat (ITT) and Per-Protocol (PP) approaches. ClinicalTrials.gov: NCT04039698. Results The authors included 144 patients, of which 54.2 % were male, mean age was 52 years. Most individuals (84.7 %) had an APRI score < 1. All patients received at least one dose of DAA, 139 completed antiviral therapy, and 131 had SVR evaluation. The ITT SVR rate was 90.3 % (130/144 patients; 95 % CI 84.2 %‒94.6 %), and the PP SVR was 99.2 % (130/131 patients; 95 % CI 95.8 %‒100 %). Eighty-three adverse events were reported, and 93 % were handled with remote care. Conclusion This simplified strategy achieved a high SVR rate in a population with restricted access to specialized care. Telehealth tools and minimal monitoring are promising components for policies aimed at HCV elimination.

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Abstract Objective This research aimed to determine the feasibility and accuracy of CLR and clinical features to formulate a prediction model for Peptic Ulcer (PU)-induced Upper Gastrointestinal Bleeding (UGIB). Methods The clinical data of 146 PU patients were prospectively collected, and patients were divided into the UGIB group (n = 48) and the non-UGIB group (n = 98). The factors affecting UGIB were analyzed using multifactorial logistic regression and collinearity analysis. The prediction model of UGIB was constructed, the predictive value of which was analyzed using the Receiver Operating Characteristic Curve (ROC) and Area Under the Curve (AUC), while the accuracy was analyzed using the calibration curve and Hosmer Lemeshow goodness-of-fit tests, and the application value was assessed using decision curve analysis (DCA). Results Statistical significance was observed between the two groups regarding HP infection, ulcer diameter, ulcer stage, use of nonsteroidal anti-inflammatory drugs, Neutrophil, LYM, NEUT/LYM Ratio (NLR), CRP, and CLR. HP infection, ulcer stage, use of NSAIDs, NLR, and CLR were independent risk factors for UGIB, and PCT was a non-independent risk factor. The AUC for this model was 0.921. The calibration curve of the model matched the actual curve. The model achieved a better fitting effect in predicting UGIB (χ2 = 8.5069, df = 8, p = 0.3856) and had a better clinical application value. Conclusion A predictive model for PU-induced UGIB, based on CLR and clinical features, can assist in developing clinical treatment plans to prevent UGIB.

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Abstract Objectives COVID-19 vaccines prevented severe disease outcomes worldwide. As part of a vaccine effectiveness study, the authors summarized demographic and health profiles, vaccination data, SARS-CoV-2 variants, and disease outcomes from patients hospitalized due to COVID-19-like symptoms in Latin America between February and December 2022. Methods LIVE was an observational-prospective study with a test-negative case-control design (NCT05282017). Adults admitted with COVID-19-like symptoms were recruited across five Latin American countries. Patients were tested for SARS-CoV-2, and variants were identified through sequencing. Data were collected from medical records and interviews. Results Participants recruited (536 cases, 250 controls) had a mean age of 60.5 years. COVID-19 cases (63.7, SD = 19.1) were slightly older than controls (53.8, SD = 20.4). Disorders of the cardiovascular system were the most prevalent comorbidities, and most participants (73.0 %) reported at least one comorbidity. COVID-19 cases mostly presented with moderate (51.1 %) disease. Overall, 50.6 % of participants were unvaccinated against COVID-19, with a higher percentage in cases (56.3 %) than in controls (38.2 %). Viral genomic analysis identified the most prevalent SARS-CoV-2 lineages, BQ.1.1 (11.9 %) among Omicron BA.5 and XBB.1.15 (2.5 %) among recombinant variants. The study was underpowered to estimate vaccine effectiveness due to the low number of COVID-19 hospitalization cases. Conclusion The present study revealed key demographic and clinical characteristics of patients hospitalized due to COVID-19. Notably, an older age among confirmed cases, a substantial proportion of unvaccinated individuals, and the decrease in hospitalizations emphasize the complexity of the COVID-19 landscape in Latin America and the need for continued research to inform public health strategies.

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Abstract Objective This study aimed to determine the cost-effectiveness of selective laser trabeculoplasty (SLT) as a replacement for hypotensive eye drops in the Brazilian Unified Health System (SUS). Methods The authors conducted a cost-effectiveness economic assessment using data from a previously published prospective, non-randomized, single-arm interventional study. The costs were estimated from the perspective of the SUS, using data from the SIGTAP. The authors proposed a value of R$ 588.00 for bilateral SLT, based on the observed cost reduction with medications in the SLT group. Effectiveness was assessed as a reduction in intraocular pressure (IOP). Results The average annual cost of medications per patient was R$ 669.53 in the reference group (continuous use of eye drops) and R$ 80.62 in the intervention group (SLT). The average IOP reduction was 9.3 mmHg in the reference group and 9.8 mmHg in the intervention group. SLT proved to be a dominant strategy compared to the continuous use of eye drops, presenting a greater reduction in IOP and a lower total annual cost. The incremental cost-effectiveness ratio (ICER) was negative (-R$ 1.82), indicating that SLT is more effective and less costly. Conclusions SLT is a cost-effective alternative to hypotensive eye drops in the treatment of glaucoma in the SUS. The adoption of SLT can optimize resource allocation and improve clinical outcomes for patients with glaucoma. Implementing SLT at the proposed procedural cost optimizes spending by substantially reducing long-term medication costs and offering a sustainable alternative within the healthcare system.

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Abstract Background Neuroblastoma is one of the most common extracranial solid tumors in children and it frequently displays high heterogeneity throughout the course of the disease. It has previously been described those changes in the ATRX gene (Alpha Thalassemia/Mental Retardation, X-linked) are the most common recurring events in the indolent clinical subtype (∼30 %) of MYCN amplified neuroblastoma. There is no effective treatment for this type of neuroblastoma, which is associated with overall poor survival. On the other hand, few studies have detected an association between high-risk (stage IV) non-amplified MYCN neuroblastoma patients and mutant ATRX. Methods In this study, 37 tumor samples from Brazilian patients with stages I to IV MYCN non-amplified neuroblastoma, according to the International Neuroblastoma Staging System (INSS), were analyzed using the panel Oncomine™ Childhood Cancer Research Assay. Results The authors found two older children (NB1 and NB2) with advanced MYCN non-amplified neuroblastoma carried each one of the two following novel nonsense ATRX variants (p.Gln1670* or p.Glu1984*). These variants created a stop codon in the helicase domain of the ATRX gene, leading to ATRX loss-of-function. These mutations were confirmed by Sanger sequencing and the protein loss-of-function was confirmed by immunohistochemistry. The finding of these heterozygous mutations in two patients with MYCN non-amplified neuroblastoma deserves further investigation. Thus, the authors analyzed each of these cases to better understand how these mutations may be related to disease severity and prognosis. Conclusion ATRX loss-of-function from p.Gln1670* or p.Glu1984* mutations turn MYCN non-amplified neuroblastoma more aggressive and similar to what is seen in MYCN amplified neuroblastoma. This information may help clinical decision-making and facilitate establishing an accurate prognosis for patients with MYCN non-amplified neuroblastoma.

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Abstract Objective This study aimed to investigate the carcinogenic role of circPOLA2 in Breast Cancer (BC) and reveal its potential mechanism as a competitive endogenous RNA. Methods Differentially expressed circRNAs, miRNAs, and mRNAs in BC tissues and cell lines were screened and analyzed by RT-qPCR. The interaction among circPOLA2, miR-1224-5p, and HMGA2 was tested using dual luciferase reporter assay and RNA pull-down assay. Cell proliferation was detected by MTT and colony formation assay, apoptosis was detected by flow cytometry, migration, and invasion was detected by Transwell assay, and EMT-related proteins were detected by Western blot. Results circPOLA2 and HMGA2 levels were elevated in BC, while miR-1224-5p level was reduced. Knocking down circPOLA2 decreased the expression of HMGA2 by elevating miR-1224-5p expression. Knocking down circPOLA2 or HMGA2 or elevating miR-1224-5p reduced the proliferative, migratory, invasive, and anti-apoptotic capacities of BC cells. Conclusion Knockdown of circPOLA2 inhibits BC cell proliferation, migration, and invasion and delays BC tumor progression by regulating the miR-1224-5p/HMGA2 axis, providing a new strategy and target for therapeutic intervention in BC.

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Abstract Objective This study aimed to evaluate the effect of Omega-3 Fatty Acids (ω-3 PUFAs) on endometriosis. Design The authors conducted a comprehensive search of the PubMed, Embase, Cochrane Library and Web of Science databases, focusing exclusively on Randomised Controlled Trials (RCTs) to study the impact of ω-3 PUFAs on endometriosis. The included studies were assessed for methodological quality using the Cochrane bias risk assessment tool and analyzed using data analysis software. Results The search yielded five RCTs conducted between the database's inception and July 2023, with a total sample size of 424 patients with endometriosis. The meta-analysis results showed no statistically significant effects of ω-3 Polyunsaturated Fatty Acids (PUFAs) on pain (Mean Difference [MD = -0.387], 95 % Confidence Interval [95 % CI -1.742-0.967], I2 = 93.3 %, z = 0.56, p = 0.575), sexual activity (MD = 0.143, 95 % CI -0.210-0.497, I2 = 0 %, z = 0.79, p = 0.427), pain intervention (MD = -0.216, 95 % CI -0.717-0.285, I2 = 0.0 %, z = 0.84, p = 0.399), catastrophic thinking (MD = 0.158, 95 % CI -0.315-0.632, I2 = 0.0 %, z = 0.66, p = 0.512) and the 12-item short form health survey (MD = 0.001, 95 % CI -0.053-0.503, I2 = 0.0 %, z = 0.00, p = 1.000), which were all statistically insignificant. However, ω-3 PUFAs appeared to reduce the inflammatory response in patients with endometriosis (MD = -5.20, 95 % CI -6.21--4.20, I2 = 0 %, z = 10.13, p < 0.001). Conclusion Based on the available evidence, ω-3 PUFAs may reduce the inflammatory response in patients with endometriosis, specifically by decreasing levels of pro-inflammatory cytokines, such as TNF-alpha, IL-6 and IL-1, indicating potential anti-inflammatory properties that warrant further investigation. Trial registration PROSPERO: CRD42023441699.

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Abstract Background The use, timing, and dosage of morphine in septic patients with a history of Chronic Heart Failure (CHF) are poorly studied, and it is still unclear if morphine administration affects sepsis survival. This study aims to elucidate the relationship between early morphine administration and 30-day mortality among septic patients with a history of CHF. Methods Utilizing data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, this retrospective cohort study focuses on septic patients with CHF. The authors investigated the effects of early morphine administration (within 24 h of ICU admission) on 30-day mortality, employing Cox proportional hazards modeling and Propensity Score Matching (PSM) for analysis. Results The authors analyzed 7424 adult septic patients with CHF, among whom 6495 received early morphine and 929 were managed without morphine. The early morphine group exhibited a significantly lower 30-day mortality rate compared to the nonmorphine group (post-matched 16.4 % vs. 25.7 %, Absolute Risk Reduction (ARR) 9.3 % (95 % Confidence Interval [95 % CI 5.1-13.6], p < 0.001). Among septic patients with CHF, early morphine administration was associated with a reduction in 30-day death in all adjusted variables (HR = 0.539‒0.735, p < 0.001). After PSM, only <15 mg of morphine was correlated to a lower 30-day mortality rate (HR = 0.233, 95 % CI 0.086-0.632, p < 0.001). Conclusion This investigation reveals a significant association between the early administration of morphine and reduced risk-adjusted 30-day mortality in septic patients with CHF.

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Abstract Objective To determine the malignancy risk of thyroid nodules with Isolated Macrocalcifications (IMC) based on surgical results and evaluate the postoperative risk of malignant nodules with IMC. Methods A total of 46 thyroid nodules with IMC were enrolled from 3680 consecutive patients who underwent thyroidectomy between August 2018 and September 2023. The malignancy risk of IMC nodules, postoperative risk of malignant nodules, and whether the ultrasonic features of IMC (smooth, lobulated, or focal disruption of the anterior margin) were associated with malignancy were investigated. The nodules were further divided into three groups (group A, maximum diameter < 10 mm; group B, maximum diameter of 10‒14 mm and group C, maximum diameter ≥ 15 mm). Differences in malignancy and Lymph Node Metastasis (LNM) risks were also evaluated among the three groups. Results The malignancy risk of the IMC nodules was 30.43% (14/46). Four patients developed LNM. Eight nodules were staged as T1aN0M0 and low-risk, whereas six nodules were staged as T1bN1aM0 and intermediate-risk. Focal disruption of the anterior margin of IMC was significantly associated with malignancy. Malignant and LNM risk showed no differences among nodules with different sizes. Conclusions IMC nodules with different sizes had a lower intermediate risk of malignancy and exhibited the same aggressive behavior. The cutoff value of these nodules for further Fine Needle Aspiration (FNA) warranted further investigation. Interruption of IMC was more often seen in malignant nodules, and more attention should be paid to these nodules.

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Abstract Background This study aimed to investigate the role of kynurenine in Colorectal Cancer (CRC) and the underlying mechanism. Methods Enzyme-linked immunosorbent assay was employed to assess the kynurenine concentration. Flow cytometry was utilized to analyze the percentages of CD3+CD4+ and CD3+CD8+ T-cells. Immunofluorescence was used to measure the expression of Programmed Death-Ligand 1 (PD-L1). RNA modification levels in CRC cells were analyzed using a dot blot assay. The interaction between NAT10 and PD-L1 was assessed via RNA immunoprecipitation, dual-luciferase reporter, and immunofluorescence assays. A xenograft tumor rat model was established. Results Results indicated that kynurenine suppressed T-cell activation and promoted immune escape. Besides, kynurenine promoted N-Acetyltransferase 10 (NAT10)-mediated N4-acetylcytidine (ac4C) modification. Moreover, NAT10 inhibition improved T-cell activation and suppressed immune escape. Mechanically, NAT10 is bound with the mRNA of PD-L1. Rescue experiments showed that PD-L1 inhibitor treatment reversed the suppressed T-cell activation and the promoted immune escape induced by NAT10 overexpression. In vivo, studies indicated that NAT10 deficiency reversed the promoted tumor growth induced by kynurenine treatment. Conclusion In conclusion, kynurenine promoted the immune escape of CRC cells via NAT10-mediated ac4C acetylation of PD-L1.

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Abstract Objectives Heart failure, especially in the elderly, is a growing global issue. This research explores the safety of human albumin infusion in treating heart failure patients with hypoalbuminemia, despite limited clinical data on its use with diuretic therapy. Methods Data were collected from the Medical Information Mart for Intensive Care III (MIMIC-III) database, which included a cohort of 6094 patients diagnosed with heart failure. Propensity score matching, logistic regression, Kaplan-Meier curves, and Locally Weighted Scatterplot Smoothing (LOWESS) curves were used to examine how albumin administration correlates with different clinical results. The evaluated results comprised in-hospital mortality, cumulative fluid output over 24 hours, Length of Stay in the Intensive Care Unit (ICU LOS), and overall hospitalization duration (hospital LOS). Results Infusing albumin was found to be markedly linked with higher in-hospital mortality among heart failure patients whose serum albumin levels were ≤ 2.9 g/dL (p < 0.001). However, no statistically significant correlation was found between the patients with levels > 2.9 g/dL (p = 0.62). Following propensity score matching in the ≤ 2.9 g/dL serum albumin group, albumin infusion was linked to prolonged hospital and ICU stays (p = 0.002, p < 0.001), but showed no significant association with total 24 hour fluid output and 90-day survival (p = 0.173, p = 0.656). Conclusion The use of albumin has been linked to increased risk-adjusted mortality during hospitalization, as well as prolonged stays in both hospital and ICU settings for patients with heart failure and low levels of serum albumin. Physicians should exercise caution when considering the administration of albumin in these cases.

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Abstract Background and objectives Sarcomas represent a heterogeneous group of malignancies characterized by varying clinical behaviors and treatment responses. Liquid biopsy has emerged as a promising non-invasive method for monitoring tumor dynamics by detecting actionable mutations in cancer patients. The emergence of circulating DNA as a non-invasive biomarker offers promising avenues for improving diagnostic accuracy and treatment monitoring in sarcoma patients. Methods In this study, the authors employed mutation-specific droplet digital PCR (ddPCR) to analyze tumor-derived cell-free DNA, also known as circulating tumor DNA (ctDNA), belonging to plasma samples of sarcoma patients, aiming to characterize mutation profiles in the IDH2 and TP53 genes. Between July 2019 and June 2023, the authors collected and analyzed 38 samples from patients diagnosed with osteosarcoma, chondrosarcoma, or Ewing's sarcoma. Histopathological confirmation of diagnoses was performed, followed by ddPCR analysis on 36 valid plasma samples. Results The results showed mutations in three out of thirty-six sarcoma patients. Patient 1 exhibited a 12.6 % mutant IDH2 (R172S) allele fraction, Patient 2 had a 0.27 % mutant TP53 (R175H), and Patient 3 showed a 17 % mutant IDH2 (R172K). Notably, Patients 1 and 2 were diagnosed with chondrosarcoma, while Patient 3 had osteosarcoma. Conclusions The present study provided evidence for the feasibility of ctDNA detection in sarcoma patients, where mutations were found in IDH2 and TP53 genes, including a novel IDH2 mutation in osteosarcoma. The evaluation of ctDNA has the potential to transform clinical strategies in this challenging group of malignancies and this may be further confirmed in larger cohort studies. Continued research efforts are essential to optimize ctDNA detection methods and validate its utility across diverse sarcoma subtypes.

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Abstract Background Alterations in 5-methyladenosine (m5C) RNA methyltransferase have been implicated in the pathogenesis of lung cancer. However, the role of NSUN3, a key m5C regulator, in modulating PD-L1 expression and immune evasion in Non-Small Cell Lung Cancer (NSCLC) remains poorly understood. Methods NSUN3 expression levels in NSCLC tissues and cell lines were quantified using quantitative Reverse Transcription PCR (RT-qPCR). The impact of NSUN3 expression modulation on lung cancer cell viability and proliferation was assessed through CCK-8 assays and colony formation experiments. To evaluate immune cell interactions, CD8+ T-cells were co-cultured with NSCLC cells, and cytotoxic activity was measured by an LDH cytotoxicity detection kit. The in vivo tumorigenic role of NSUN3 was investigated using subcutaneous tumor xenograft models. Mechanistic insights into NSUN3-PD-L1 interactions were obtained through m5C-RIP, RIP, and dual-luciferase reporter assays. Results Elevated NSUN3 mRNA levels were observed in NSCLC tissues compared to normal controls. Functional studies demonstrated that NSUN3 knockdown significantly inhibited cell viability and proliferation in both A549 and PC9 cell lines. Furthermore, NSUN3 depletion enhanced CD8+ T-cell-mediated cytotoxicity against NSCLC cells and suppressed tumor growth in vivo. Mechanistically, NSUN3 inhibition was found to stabilize PD-L1 mRNA, suggesting a regulatory role in immune checkpoint modulation. Conclusions The present findings establish NSUN3 as an oncogenic driver in NSCLC pathogenesis, functioning through PD-L1 mRNA stabilization. The identification of this NSUN3-PD-L1 regulatory axis provides new insights into the molecular mechanisms underlying immune escape in NSCLC and offers promising directions for developing targeted immunotherapies.

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Abstract Background Generalized Anxiety Disorder (GAD) is a common and disabling psychiatric disorder that negatively impairs patients' quality of life. Studies suggest that inadequate consideration of interpersonal problems may contribute to the poor treatment response in psychotherapy for GAD. Interpersonal Psychotherapy (IPT) is an evidence-based psychosocial intervention that focuses on symptoms by improving interpersonal functioning, and research demonstrates that IPT is efficacious in treating social anxiety and panic disorders. To date, however, there are no studies examining IPT for patients with GAD. Methods The authors developed and pilot-tested an IPT manual for the treatment of GAD in groups with two cohorts of patients. Pre- and post-test measures of anxiety were collected and analyzed. Results The authors successfully developed a treatment manual for Group IPT for Anxiety using iterative qualitative methods. Significant improvement from baseline was noted in the GAD scores for patients in both patient cohorts. Conclusions The results suggest that IPT can be successfully used for GAD in group formats and that future large-scale randomized trials should be warranted. The results also suggest that online group therapy is feasible and warrants further study and that it may be used to deal with access and logistical barriers faced by many patients.

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Abstract Objective To characterize practices and knowledge regarding PA counseling at a large tertiary hospital. Design Cross-sectional observational study. Participants and setting Physicians with an active medical practice within the university hospital were invited to respond to an online survey. Interventions A questionnaire designed to capture information on medical training, life habits and knowledge about PA. Main outcomes measures Sedentary behavior, clinical practice and self-efficacy were assessed by Likert-type questions, whereas regular practice, previous training, and knowledge of PA were evaluated through dichotomous questions (answers: “yes or no” or “true or false”). Results Response rate was 11.5 % (50.6 % female, 44.9 ± 12.8 years), 67.7 % were physically active, and 63.3 % had 4 to 8 h/day of sedentary behavior. Only 40.7 % had previous training on PA, 99.7 % recognized the importance of recommending PA, but only a small part (48.4 %) recommended PA in all consultations (the main barrier was lack of specific training). In addition, 69.2 %, 58.7 % and 65.5 % rated their abilities to collect PA history, assess contraindications, and engage the patient as good/excellent, respectively. Knowledge of PA was rated as low to very low, with correct answers ranging from 49 % to 17 % and as low as ∼10 % (when considering the pediatric population). Conclusion Although physicians recognize the importance of PA counseling and have high perceived self-efficacy in relation to counseling skills, few put them into practice. This may be due to insufficient training on PA and/or the complexity of services provided at the tertiary hospital. The present results corroborate the need for improvements in medical training on PA.

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Abstract Objective Examination of the current status of acute fatigue in patients with acute ischemic stroke and analysis of contributing factors. Methods A convenience sampling method was utilized to recruit 420 patients diagnosed with acute ischemic stroke, who were admitted to the affiliated hospital of Putian University in Fujian Province, China, between October 2022 and December 2023. Data collection involved the administration of a general information questionnaire, the Fatigue Severity Scale (FSS), the Fear of Progression Questionnaire (FoP-Q-SF), the Perceived Social Support Scale (PSSS), the Barthel Index, and the Modified Rankin Scale (MRS). Results The mean score for Post-stroke Fatigue (PSF) was 3.08 ± 1.52, and the prevalence rate of elevated PSF was 37.4 %. Unconditional logistic regression analysis revealed that social support functioned as a protective factor against fatigue in patients with acute ischemic stroke. Conversely, being female, having chronic comorbidities, having a stroke located in the basal ganglion, high Modified Rankin Scale (MRS) scores, poor self-care ability, and fear of disease progression were identified as risk factors for fatigue (p < 0.05 or p < 0.01). Conclusion Perceived Stress Factor (PSF) is a common and serious consequence following stroke, which considerably impacts patients’ recovery and overall quality of life. Consequently, clinical practice should prioritize the identification and management of PSF through early intervention and targeted therapeutic strategies to enhance patient prognosis and quality of life. Additionally, further research is warranted to investigate the underlying biological mechanisms of PSF and to develop potential intervention strategies. This study adopted a cross-sectional research design.

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Abstract Objectives Oncology has exhibited gender inequalities in leadership and authorship, alongside significant differences in cancer incidence, mortality, and survival rates between sexes. These disparities highlight the urgent need for sex- and gender-specific scientific reporting to improve research accuracy and clinical applications and encourage the same opportunities in research careers. Methods The integration of gender perspective in cancer was assessed by analyzing scientific publications comparing 2011 and 2021. The correlation between the gender of the authors and the different types of cancer studied was examined, as well as the inclusion of the sex and gender variables in the content of the research. The study was STROBE compliant. Results 3,194 papers were published in 2011 and 6,781 in 2021, signed by at least one Spanish institution. The ratio of female authors per article was 0.39 in 2011 compared to 0.43 in 2021, reaching parity. Gender bias in the content of scientific articles, as measured by a 10-item checklist, showed an unfavorable score for perspective integration in both years (1.7/10 and 1.8/10, respectively). In terms of the Gender Balance Index in the analyzed samples of the papers (cells, animals or volunteers/patients), there was an increase from 29 % in 2011 to 43 % in 2021. Breast cancer research was dominated by female authors, whereas lung cancer research was predominantly by parity or male authorship, and no differences in author groups in colorectal cancer research were observed. Conclusions Greater efforts and commitments are needed from government institutions, funding agencies, and academic structures to promote sex/gender integration in cancer research.

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Abstract Objectives To investigate the practicality, accuracy, and consistency of a computer-based Optokinetic Nystagmus (OKN) analyzer for vision diagnosis in preschoolers. Design A comparative study evaluating the performance of a computerized OKN analyzer against the traditional E-word visual acuity chart in assessing visual acuity in preschool children. Participants A total of 138 children aged 2 to 6 years were enrolled in the study, divided into five age groups: 2 years (29 children), 3 years (27 children), 4 years (28 children), 5 years (28 children), and 6 years (26 children). Methods Visual acuity was tested using both the nystagmus meter and the E-word visual acuity chart. Statistical analyses, including correlation coefficient calculation and chi-square tests, were conducted to evaluate the testability and consistency of the methods. Results Out of 138 participants, 125 (90.6 %) successfully completed the test using the computerized OKN analyzer. There was no significant difference in the measurability across different age groups. The testability of the E-word visual acuity chart was significantly lower at 71.0 %. A strong correlation (R = 0.872) was found between the results from the nystagmus meter and the E-word visual acuity chart, indicating high consistency between the two methods. Conclusion The computerized OKN analyzer is a reliable, accurate, and practical tool for assessing visual acuity in preschoolers. It offers a non-invasive alternative to traditional methods, with high testability and strong correlation with standard visual acuity tests, making it a valuable tool for early detection of vision impairments in young children.

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Abstract Background Endometrioid Endometrial Carcinoma (EEC), an estradiol-related disease, remains a serious health threat to women because of its high incidence and trend of rejuvenation. Accumulating evidence has highlighted that microRNAs (miRNAs) and messenger RNAs (mRNAs) play important roles in various biological processes involved in the pathogenesis of EEC. This study aimed to identify the potential prognostic biomarkers associated with EEC regulated by estradiol. Methods RNA expression profiles of EEC were obtained from The Cancer Genome Atlas database (n = 408) and the original sequencing, which was performed on endometrial cancer Ishikawa cells treated with 250 nM estradiol (n = 3), 50 nM estradiol (n = 3) or control (n = 3). The TargetScan database was used to predict the target genes of prognosis-related differentially expressed miRNAs (DEMs). Subsequently, functional enrichment analysis and topological analysis were performed on the overlaps of target genes and differentially expressed mRNAs (DEGs). Kaplan-Meier analysis was used to predict prognosis‐related target genes to identify prognostic biomarkers and cell population landscapes, and gene expression analysis was performed to locate prognosis-related DEGs based on single-cell transcriptomic sequencing data from the NCBI Sequence Read Archive database. Results Four estradiol-related DEGs were associated with prognosis, and 235 overlapping target DEGs were screened and incorporated into the functional enrichment analysis and protein-protein interaction network visualization studies. Additionally, SACS and GPR157 were identified as potential biomarkers for EEC prognosis through survival analyses. Furthermore, single-cell transcriptome data were analyzed to show changes in gene expression levels in specific cell types. Conclusions This study demonstrates that miR-142-5p-SACS and miR-30a-5p-GPR157, which are regulated by estradiol, may hold promise as diagnostic and prognostic biomarkers and novel therapeutic targets for EEC.

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Abstract Objective To explore the association of obesity comprehensively defined by Body Mass Index (BMI) and Body Fat percentage (BF%) with osteopenia. Methods In this cross-sectional study, data of adult men and postmenopausal women aged ≥ 50 years old were obtained from the National Health and Nutrition Examination Surveys (NHANES) database. Weighted logistic regression analysis was conducted to investigate the association of BF% obesity with osteopenia in participants who had different gender and BMI obesity conditions. The association of obesity comprehensively evaluated by BMI and BF% with osteopenia was also explored in the total population and in gender subgroups. Results Among 1720 eligible subjects, 1054 had osteopenia. Multivariate analysis suggested that in males, BMI obesity combined with BF% obesity was associated with higher osteopenia odds compared to BMI obesity only (Odds Ratio [OR = 4.01], 95% Confidence Interval [95% CI 1.43‒11.27]). Compared to participants with both BMI and BF% obesity, those with BMI obesity have lower osteopenia odds (OR = 0.46, 95% CI 0.28‒0.76), whereas those with BF% obesity have higher odds of osteopenia (OR = 2.03, 95% CI 1.35‒3.05, p = 0.002). In females, compared to BMI obesity combined with BF% obesity, BF% obesity (OR = 3.37, 95% CI 1.47‒7.73) or non-obesity (OR = 2.11, 95% CI 1.18‒3.75) was respectively associated with higher osteopenia odds. In males, BMI obesity was linked to lower osteopenia odds compared to both BMI and BF% obesity (OR = 0.25, 95% CI 0.10‒0.62). Conclusions The comprehensively assessed obesity by BMI and BF% may be more meaningful in the evaluation of potential osteopenia risk, as well as further prevention and intervention of osteoporosis.

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Abstract Background This study aimed to investigate the effects of LDE-MTX on acute cerebral infarction. The study focuses on how LDE-MTX can influence the outcomes of ischemic stroke in a rat model, specifically examining its neuroprotective properties. Methods Radioactively labeled LDE uptake by brain tissue was determined after IV injection in rats with Endothelin-1 (ET-1)-induced cortical ischemic stroke (n = 11) and controls (n = 18). Two groups of 5 animals were treated with LDE-MTX (1 mg/kg, IV) or LDE-alone 4 h post-stroke induction. After 7days, tissues were analyzed by immunohistochemistry for neuronal bodies, astrocytes, and microglia. Results LDE uptake was fivefold higher in ischemic rats than in controls (p = 0.0003). LDE-MTX significantly inhibited microglial activation, resulting in a tenfold decrease in activated macrophages, and increased neuronal survival by 319 % in the periinfarct area. LDE-MTX had no effect on astrocytosis or primary infarct size. Conclusions LDE-MTX demonstrated neuroprotective effects and shows potential as a novel strategy to limit ischemic stroke damage. The results suggest that LDE-MTX could be a promising treatment option for reducing ischemic damage in stroke patients, particularly through its effect on microglial activation and neuronal survival.

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Abstract Objective Retinoblastoma (RB) is a type of intraocular tumor in childhood with a high lethality rate. N4-acetylcytosine (ac4C) modification is known to regulate multiple cancers, which is mediated by the only known ac4C writer N-Acetyltransferase 10 (NAT10). In this study, the authors aimed to reveal the mechanism of RB progression regulated by ac4C modification. Method Phenotypically, dot blot assay and quantitative real-time PCR were used to detect the ac4C levels and NAT10 expression in clinical samples and RB cell lines. Then, NAT10 was knocked down to assess its effect on glycolysis. Mechanically, RNA immunoprecipitation assay, immunofluorescence assay, and dual luciferase report were used to explore the mRNA modified by NAT10-mediated ac4C modification. Mice xenograft model was used to determine the effect of NAT10 on tumor growth in vivo. Results The present results demonstrated that the levels of ac4C and NAT10 were increased in cancer tissues and RB cell lines. Furthermore, NAT10 knockdown inhibited the glycolysis in RB cell lines. Moreover, the authors revealed that NAT10 knockdown decreased the ac4C modification and mRNA stability of HK1, while the inhibition of glycolysis by NAT10 knockdown was reversed by HK1 overexpression. Finally, NAT10 knockdown relieved the growth of tumors in mice models. Conclusion The authors illustrated that NAT10 plays an important role in the progression of RB by regulating the ac4C modification on HK1 mRNA and affects its stability, which may provide a novel theoretical basis for the treatment of RB.

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Abstract Objective Chest wall reconstruction plays an important role in the outcomes of chest wall resection. However, there being a huge variety of materials at disposable, the best option has not yet been well defined. The Vitagraft® is a synthetic and absorbable material, that works as an osteoinduction and osteoconduction for bone regeneration. It consists of a β-phase Tricalcium Phosphate Ceramic (β-TCP) and the Polylactic Glycolic Acid Polymer (PLGA). Therefore, this study intends to assess the safety of Vitagraft® use in the chest wall. Methods A prospective study, in which the patient’s chest was reconstructed with Vitagraft®. Each patient was followed after the procedure for at least three months. The following variables were considered: KPS, ECOG, preoperative treatment, defect size, myocutaneous flap, the time between surgeries, complications, and mortality. Results Eight resections were performed due to tumor findings. One reconstruction was a treatment for sternal cleft, another for Poland’s syndrome, and finally as a consequence of late sternal dehiscence. Primary closure was performed in 63.6 % of the patients. Vitagraft® was used in association with mesh in eight cases. Reoperation was required in two cases, and prosthesis removal for one of them. Respiratory failure and major systemic complications were not evidenced. Conclusion In the present study, the first to assess Vitagraft® in chest wall reconstruction, the second operation was necessary for 28 %, and removal was mandatory for 14 %. Until now, chest postoperative tomography has been showing good prosthesis biocompatibility. The authors need further details about the ossification time especially relating to the size of the resection.

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Abstract Objective To evaluate the performance of Grayscale Ultrasound (GSU), Color Doppler Ultrasound/Power Doppler Ultrasound (CDU/PDU), Transrectal Real-Time Tissue Elastography (TRTE) and Contrast-Enhanced Ultrasound (CEUS) in the diagnosis of Prostate Cancer (PCa). Method All analyzed patients underwent GSU, CDU/PDU, TRTE and CEUS examinations before radical prostatectomy. Receiver Operating Characteristic (ROC) curves were drawn, and the Areas Under the Curve (AUCs) were calculated for the four ultrasonic modalities alone and in combination. Binary logistic analysis was used to evaluate the predictive value of lesion features observed with the 4 modalities. Results The results of the chi-square test showed that the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy rate of TRTE for diagnosing PCa were higher than those of CEUS (p-values were < 0.05 for all). The ROC curves analysis showed that the diagnostic performance of TRTE for PCa was better than that of CEUS (p = 0.046). Moreover, the diagnostic performance of the combination of four ultrasonic technologies (AUC = 0.873) was significantly better than that of any technology alone. Multivariate binary logistic regression analysis showed that enhancement strength on CEUS, presence of a blue area on TRTE and total serum Prostate Specific Antigen (PSA) level were independent predictors for prostate malignancy. Conclusions The diagnostic performance of TRTE was higher than that of CEUS. Early hyperenhancement on CEUS and stiffness on TRTE had high predictive value for the diagnosis of PCa. The combination of multiple ultrasonic modalities can significantly improve the positive diagnostic rate for PCa over that of a single ultrasonic mode.

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Abstract Background Existing systematic reviews provide evidence that art therapy is an effective intervention for reducing symptoms of depression in children and adolescents. This study aims to systematically review and quantify the impact of art-based interventions on depressive symptoms in this demographic through meta-analysis. Method A systematic search of databases and journals identified eligible studies for inclusion in a meta-analysis examining the efficacy of art therapy interventions on depressive symptom reduction. A random-effects meta-analysis was conducted using the Standardized Mean Difference (SMD). Results The meta-analysis of twelve (randomized) controlled trials revealed a significant effect (SMD = -0.72; 95 % CI [-1.28, -0.16], p = 0.01), indicating that children and adolescents (n = 333) who received art therapy experienced a more significant reduction in depressive symptoms compared to those (n = 344) in the control groups. Limitations The existing evidence is limited to studies with low statistical power and methodological quality. Furthermore, the included studies were highly heterogeneous in terms of the intervention type, measurement tools, participant samples, and study designs. Conclusions The findings suggest that art-based interventions can be effective in reducing depressive symptoms in children and adolescents. However, future research requires more methodologically rigorous and well-controlled studies to strengthen the evidence base.

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Abstract Background and objectives Fatty liver disease is often associated with renal impairment in many patients. Early detection and prompt intervention are crucial for improving patient quality of life and reducing mortality rates. This study aimed to develop and validate a nomogram for detecting the risk of Chronic Kidney Disease (CKD) comorbidity in adults with Nonalcoholic Fatty Liver Disease (NAFLD) in the United States. Methods From the NHANES (2017‒2020) database, the authors enrolled 2848 NAFLD participants, of whom 633 also had CKD. The authors employed the Least Absolute Shrinkage and Selection Operator (LASSO) regression and multivariate logistic regression to identify variables with predictive value. The overlapping features were selected to construct a predictive model, which was presented as a nomogram. The effectiveness of the nomogram was evaluated using Receiver Operating Characteristic (ROC) curves, calibration plots, and decision curve analysis. Results Six indicators were included in the model: age, systolic blood pressure, serum albumin, high-sensitivity C-reactive protein, total cholesterol, and triglycerides. The area under the curve of the nomogram for predicting CKD in the training set was 0.772, with a 95 % Confidence Interval (95 % CI) of 0.746 to 0.797. In the validation set, the area under the curve was 0.722, with a 95 % CI of 0.680 to 0.763. The calibration curve analyses demonstrated that the prediction outcomes of the model aligned well with the actual outcomes, indicating good clinical applicability. Conclusions The nomogram demonstrated excellent performance and has the potential to serve as an auxiliary tool for detecting CKD in NAFLD patients.

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ABSTRACT Objective To explore the effects of Baihu Guizhi decoction on the degree of joint swelling and levels od inflammatory cytokines in rats with Acute Gouty Arthritis (AGA). Method AGA was induced by injecting sodium urate crystal solution into the ankles of rats. After the successful preparation of the model, Baihu Guizhi's decoction was given. Ankle swelling index, joint dysfunction index, and inflammation index were measured. The rats were euthanized and the synovial tissue of the knee joint was collected. Nuclear Factor-κB (NF-κB) in the synovium was detected by immunohistochemical method. Meanwhile, TNF-α, IL-1β, and IL-6 levels were detected by ELISA in the abdominal aorta. TLR4 and MyD88 were measured by RT-qPCR and Western blotting in the synovial tissue. Results In AGA rats, the diameter of the right ankle joint and levels of TNF-α, IL-1β, and IL-6 in joint soft tissues were increased. Baihu Guizhi decoction decreased ankle swelling index, relieved inflammation, and reduced TLR4 and MyD88 expression, while these effects could be further enhanced by miR-17–5p-mimics. NF-κB expression in the synovium was reduced by Baihu Guizhi decoction, especially by Baihu Guizhi decoction + miR-17–5p-mimics. Conclusions Baihu Guizhi decoction can alleviate the joint inflammation of AGA rats by targeting miR-17–5p to regulate the TLR4/Myd88/NF-κB signaling pathway and reduce inflammatory responses.

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ABSTRACT Background The circadian system plays a crucial role in managing cardiovascular functions, with disturbances in this system associated with Myocardial Infarction (MI). Despite this connection, the exact mechanisms by which clock genes influence MI occurrence are not well-defined. This research focused on investigating the link between clock genes and MI. Methods The authors examined MI microarray datasets (GSE151412 and GSE60993) from the GEO database, concentrating on Differentially Expressed Genes (DEGs) associated with the circadian system. To clarify critical biological functions and pathways, the authors performed enrichment analyses using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Through Lasso regression, the authors pinpointed hub genes and confirmed their relevance using both the GSE66360 dataset and quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR). Furthermore, the authors conducted single-Gene Set Enrichment Analysis (GSEA) to reveal pathways linked to the hub gene. The analysis extended to exploring drug interactions and networks involving competing endogenous RNA (ceRNA). Results The present analysis identified ten clock genes associated with circadian rhythms that showed differential expression between MI patients and healthy controls. Enrichment analysis suggested these genes’ roles in pathways like the Gap junction and circadian rhythm pathways. Following Lasso regression and validation, RPS27A was identified as the main hub gene. GSEA further highlighted enriched pathways, such as mismatch repair. Additionally, immune infiltration analysis revealed notable differences in B-cell and CD4+ T-cell populations between the MI group and the control group. Conclusion The present findings suggest that the clock-related gene RPS27A is associated with MI, potentially influencing its development through circadian rhythm regulation. These results enhance the understanding of MI pathogenesis and may offer new avenues for therapeutic intervention.

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ABSTRACT Objectives Meditation has been shown to influence physical and psychological health and well-being, modulating stress response, resilience, emotional regulation, mood, empathy, compassion, and improving quality of life. The authors aim to characterize the psychosocial profile of experienced practitioners of Meditation on the Essence of Self, the Gurusakásha, whose technique is based on visualization and mantra from the Indian tantric tradition. Methods Meditation experts (n = 23) were paired to an age-, gender- and educational level-matched control group (n = 29). Clinical data (presence of baseline diseases, use of medications, habits), stress level (PSS), resilience (CD-RISC), subjective mood states (VAMS), empathy (IRI), quality of life (WHOQOL-BREF), and general lifestyle profile (PEVI) were compared between groups. Results Experienced meditators had lower levels of perceived stress, and better scores on resilience, empathic concern, quality of life, and lifestyle profile suggesting that Meditation on the Essence of Self improves health and well-being. Conclusions These results suggest that experienced meditators on the Essence of Self have higher levels of psychological well-being and quality of life when compared to non-meditators.

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ABSTRACT Objective To investigate the mechanism by which circHIPK3 enhances FASN stability by inhibiting the ubiquitinated degradation of ALYREF on Gallbladder Cancer (GBC). Methods RT-qPCR was performed to detect circHIPK3 in GBC tissues and to analyze the relationship between circHIPK3 and clinicopathological characteristics of GBC patients. CCK-8 and colony formation assays were performed to study the proliferation of GBC cells, flow cytometry to detect apoptosis, tube formation assay to test angiogenesis, and Transwell assay to study migration and invasion. A nude mice implantation assay was conducted. CircHIPK3, FASN and SKP2 were assessed using RT-qPCR and western blot. Ubiquitination assay was performed to detect ALYREF ubiquitination, and RNA pull-down and RIP to investigate the binding relationship between circHIPK3, ALYREF and FASN. Results CircHIPK3 was upregulated in GBC tissues, with elevated expression correlating with TNM stages and lymph node metastasis. CircHIPK3 knockdown suppressed GBC progression by inhibiting proliferation, angiogenesis, migratory and invasive capacity while promoting apoptosis in vitro, paralleled by reduced tumor growth in vivo. CircHIPK3 stabilized ALYREF via inhibiting ubiquitination-mediated degradation. ALYREF knockdown phenocopied the tumor-suppressive effects of circHIPK3 depletion, whereas ALYREF overexpression rescued circHIPK3 knockdown-induced suppression of malignant phenotypes. CircHIPK3 stabilizes FASN mRNA through ALYREF. Overexpressing FASN counteracted the actions of circHIPK3 downregulation on cellular angiogenesis and apoptosis. Conclusion CircHIPK3 enhances FASN stability by inhibiting ALYREF ubiquitination degradation, promoting angiogenesis, and inhibiting apoptosis in GBC. This study positions circHIPK3 as a promising prognostic biomarker and therapeutic target in GBC, with ALYREF and FASN emerging as critical mechanistic nodes within this oncogenic pathway.

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ABSTRACT Objectives To evaluate the impact of Fiberoptic Bronchoscopy (FOB) with Bronchoalveolar Lavage (BAL) on infection control in patients with severe Ventilator-Associated Pneumonia (VAP) and compare it with conventional treatments to provide a reliable basis for clinical therapy. Method This retrospective study included 86 patients with severe VAP who were admitted to the hospital between November 2019 and June 2023. Based on the treatment regimen, the patients were divided into two groups: a control group (conventional lavage and suction therapy, n = 32) and an observation group (FOB with BAL, n = 54). Results The bacterial clearance rate of the observation group was significantly higher than in the control group (87.93 % vs. 70.27 %, p < 0.05). On days 5 and 7 post-treatment, the CPIS scores of the observation group were markedly lower than those of the control group (p < 0.05). After Post-treatment, the observation group demonstrated significantly superior respiratory mechanics (PIP, Cdyn, Raw), blood gas analysis parameters (PaO2, PaO2/FiO2, PaCO2), and pulmonary function indicators (PEF, PEEPi) compared to the control group (p < 0.05). The levels of inflammatory markers in the observation group were notably reduced (p < 0.05). Additionally, the duration of mechanical ventilation, infection control, and length of stay were significantly shorter in the observation group (p < 0.05). There was no significant difference in the incidence of complications between the two groups (p > 0.05). Conclusions FOB with BAL as adjunctive therapy for VAP demonstrated significant advantages in enhancing respiratory mechanics, pulmonary function, blood gas analysis, inflammatory response, and bacterial clearance rate while effectively reducing mechanical ventilation duration and length of stay.

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ABSTRACT Objective To investigate the incidence of postoperative venous thromboembolism in women with uterine adenomyosis treated using different surgical methods, and to evaluate the associated clinical and laboratory parameters, including thromboembolism assessment after laparoscopic excision of adenomyosis. Methods (1) A retrospective collection of clinical data was conducted for 411 women with uterine adenomyosis and 33 women without adenomyosis who underwent surgical treatment at Hubei Provincial Maternal and Child Healthcare Hospital from March 2020 to December 2022. The clinical data, surgical methods, and preoperative and postoperative coagulation parameters were compared between the two groups. (2) The incidence of venous thromboembolism in women with and without uterine adenomyosis was analyzed. (3) The differences in the incidence of venous thromboembolism among women with uterine adenomyosis who underwent different surgical methods were analyzed, including clinical data and preoperative and postoperative coagulation parameters of women who did not experience venous thromboembolism. (4) The incidence of venous thromboembolism was compared between women receiving mechanical thromboprophylaxis and those receiving a combination of mechanical and pharmacological prophylaxis. Results (1) Comparative analysis of clinical data showed that women with uterine adenomyosis had fewer pregnancies and births, lower hemoglobin levels, and larger uterine volumes compared to women without adenomyosis (p < 0.05). There were no significant differences in preoperative and postoperative coagulation parameters between the two groups (p > 0.05). (2) The preoperative platelet count and postoperative d-dimer levels were higher in women with uterine adenomyosis than in those without adenomyosis (p < 0.05). (3) The incidence of venous thromboembolism was higher in the uterine adenomyosis group (9.78 %) than in the non-adenomyosis group (3.03 %). Among the women with uterine adenomyosis, the incidence of venous thromboembolism after laparoscopic lesion excision (18.46 %) was higher than that after laparoscopic hysterectomy (7.86 %). (4) Compared with the mechanical prophylaxis group, the mechanical plus pharmacological prophylaxis group had a significantly lower incidence of venous thromboembolism [18.52 % (15/81) vs. 7.62 % (25/328)], with a statistically significant difference (p < 0.05). Conclusion The incidence of postoperative venous thromboembolism is relatively high in women with uterine adenomyosis, particularly in those who underwent laparoscopic lesion excision. Even in the absence of typical symptoms and despite thromboprophylaxis, screening for venous thromboembolism should be considered within 7 days postoperatively.

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ABSTRACT Objective To explore the relationship between PIK3CA mutations and clinicopathological features and prognosis in breast cancer patients. Methods This retrospective cohort study included 283 patients with invasive breast cancer who underwent surgery from June 2017 to June 2022. PIK3CA exon 9 and 20 mutations were detected using PCR and sequencing. Patients were divided into recurrence (n = 47) and non-recurrence (n = 236) groups based on follow-up data to identify postoperative recurrence factors and build a prediction model. Kaplan-Meier analysis was used to evaluate recurrence rates. Results PIK3CA mutations were identified in 41% of patients, with exon 20 mutations being the most common (62.1%). Mutations correlated with tumor quadrant, histological subtype, clinical stage, perineural invasion, and high NLR (p < 0.05). Recurrence group patients showed higher BMI, multiple tumors, non-luminal types, advanced clinical stage, lymph node metastasis, and higher NLR (p < 0.05). Multivariate analysis identified high BMI, multiple tumors, lymph node metastasis, advanced clinical stage, and perineural invasion as independent recurrence risk factors (p < 0.05). Notably, no significant difference in disease-free survival was observed between PIK3CA mutant and wild-type patients (p > 0.05). Conclusion PIK3CA mutations are associated with specific clinicopathological features but do not significantly impact prognosis in breast cancer patients.

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ABSTRACT Background Improving diagnostic accuracy in EBUS image analysis using machine learning is a current challenge. This study aimed to identify the most effective transfer learning model for predicting lymph node malignancy. Methods EBUS images collected between 2020–2023 were retrospectively analyzed. Demographic data, sampled lymph nodes, and pathology results were retrospectively collected from the files. Eight pre-trained CNN models (VGG, ResNet, InceptionNet, Xception, MobileNet, DenseNet, NasNet, EfficientNet) were evaluated. Results The study shows that the VGG19, EfficientNetV2L and DenseNet201 models have the highest performance in malignancy prediction, achieving areas under the curve of 0.96, 0.96 and 0.95 respectively, with consistent training and testing accuracy, indicating successful models without overfitting. In contrast, the ResNet152V2, Xception, and NasNet models show lower performance with areas under the curve of 0.88, 0.85, and 0.84 respectively, indicating overfitting due to discrepancies between training and test data. The MobileNetV2 model, with an area under the curve of 0.50, fails to discriminate between benign and malignant cases, resulting in an accuracy of only 0.51. Conclusions The application of transfer learning to the analysis of EBUS images offers significant potential for improving diagnostic accuracy in thoracic medicine, particularly in lung cancer.

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ABSTRACT Objective This study aimed to analyze cesarean section rates among women with GDM classified according to the Robson system and to identify independent factors associated with vaginal delivery. Method A retrospective cohort study was conducted with pregnant women receiving care at the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, between 2012 and 2020. A total of 1508 pregnant women with GDM were included and divided into two groups based on the mode of delivery. Statistical analyses were performed to assess differences between groups and identify predictive factors for vaginal delivery using Binary logistic regression. Results The overall c-section rate was 65.3 %. Robson group 5 was the most representative, accounting for 39.53 % of all cesarean deliveries, with a single previous uterine scar being the primary indication (40.2 %). Spontaneous labor onset was the strongest independent predictor of vaginal delivery (OR = 8.601, 95 % CI 6.029–12.270), whereas previous cesarean delivery (OR = 0.093, 95 % CI 0.065–0.134), fetal distress (OR = 0.110, 95 % CI 0.071–0.171), and multiple pregnancy (OR = 0.096, 95 % CI 0.036–0.259) significantly reduced this likelihood. Conclusions The high cesarean section rate among women with GDM, particularly in group 5, highlights the importance of previous uterine scar in determining the mode of delivery in this population. Encouraging spontaneous labor onset, provided that maternal and fetal conditions are adequately monitored, may be an effective strategy to reduce unnecessary cesarean sections in pregnancies complicated by GDM.

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ABSTRACT Introduction Pancreatic Fistula (PF) is a major complication following Pancreatoduodenectomy (PD), making its prediction crucial for individualized treatment. The aim of this study is to develop a preoperative nomogram to predict PF after PD. Material and methods From January 2009 to January 2018, patients who underwent PD were reviewed. Variables with p < 0.1 from univariate analysis were selected for a multivariate analysis. Variables with p < 0.05 were then included in the nomogram, which was internally validated in a different group of patients. Results 262 patients underwent PD during the period of the study. The risk factors for PF identified in the derivation group were male gender (OR = 2.89), higher BMI (OR = 1.14) and pancreatic duct diameter ≤ 3 mm (OR = 3.52). Preoperative weight loss exceeding 10 % within six months was protective against PF (OR = 0.16). A preoperative nomogram incorporating these four variables was developed and demonstrated good performance in the validation set, with an area under the ROC curve of 0.798. Conclusions male gender, a main pancreatic duct ≤ 3 mm and higher BMI are risk factors for PF, while weight loss is protective. The developed nomogram accurately predicts PF occurrence using these variables.

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Abstract Objective To investigate the causal associations between 41 circulating inflammatory factors and Tic Disorders (TD) via the Mendelian Randomization (MR) approach. Methods Single-Nucleotide Polymorphisms (SNPs) related to 41 circulating inflammatory factors were obtained from published Genome-Wide Association Studies (GWASs). The outcome event, TD, was sourced from the FinnGen Biobank database. MR was employed to explore the causal relationship between these inflammatory factors and TD. Causal inference was performed via Inverse Variance Weighted (IVW), MR-Egger, and Weighted Median (WM) methods. Heterogeneity was assessed by Cochran's Q statistic and the leave-one-out method. Horizontal pleiotropy was examined with MR-Egger regression and MR-PRESSO. SNPs with horizontal pleiotropy were removed via the PhenoScanner database to ensure result reliability. Results MR analysis revealed significant causal associations between three circulating inflammatory factors and TD. Increased levels of Interleukin-17 (IL-17) and macrophage Migration Inhibitory Factor (MIF) were associated with an increased risk of TD (OR = 2.329, 95 % CI [1.069-5.078], p = 0.033; OR = 2.267, 95 % CI [1.097-4.686], p = 0.027), whereas increased levels of Platelet-Derived Growth Factor BB (PDGF-BB) were linked to a reduced incidence of TD (OR = 0.750, 95 % CI [0.387-1.453], p = 0.023). No causal relationships were found for other inflammatory factors. No heterogeneity or horizontal pleiotropy was detected during the study, and the MR statistical power (power > 80 %) confirmed the reliability of these three findings. Conclusion MR analysis revealed causal links between IL-17, MIF, PDGF-BB and TD, suggesting important clinical implications for the development of targeted prevention and treatment strategies for TD.

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Abstract Objective This work analyzes the effect of the combination of Oxytocin (OXT) combined with cervical balloon dilators on stress injury indicators and inflammatory factors in pregnant women with high-risk pregnancies. Methods Ninety-three pregnant women with high-risk pregnancies from June 2021 to November 2023 were collected and analyzed retrospectively, of which 43 cases were induced by OXT (control group), and 50 cases were induced by OXT combined with cervical balloon dilators (observation group). The differences in blood pressure and Heart Rate (HR) between the two groups were compared, and the pre-and post-treatment oxidative stress indicators Norepinephrine (NE), Adrenaline (AD), and Cortisol (Cor) and the inflammatory factors Tumor Necrosis Factor-α (TNF-α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6), and Prostaglandin E2 (PGE2). In addition, postpartum complications were counted in both groups. Results The observation group had higher BP and lower HR than the control group (p < 0.05). After treatment, NE, AD, Cor, TNF-α, IL-1β, IL-6, and PGE2 increased in both groups, but the observation group was lower than the control group (p < 0.05). In addition, there was no difference in the incidence of postpartum complications between the observation group and the control group (p > 0.05). Conclusion OXT combined with cervical balloon dilators can effectively ameliorate oxidative stress injury and reduce inflammatory response in high-risk pregnancy women.

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Abstract Purpose: Alzheimer’s disease is a debilitating neurological disorder that requires accurate diagnosis for the most effective therapy and care. Methods: This article presents a new vision transformer model specifically created to evaluate magnetic resonance imaging data from the Alzheimer’s Disease Neuroimaging Initiative dataset in order to categorize cases of Alzheimer’s disease. Contrary to models that rely on convolutional neural networks, the vision transformer has the ability to capture large relationships between far-apart pixels in the images. The suggested architecture has shown exceptional outcomes, as its precision has emphasized its capacity to detect and distinguish significant characteristics from MRI scans, hence enabling the precise classification of Alzheimer’s disease subtypes and various stages. The model utilizes both the elements from convolutional neural network and vision transformer models to extract both local and global visual patterns, facilitating the accurate categorization of various Alzheimer’s disease classifications. We specifically focus on the term ’dementia in patients with Alzheimer’s disease’ to describe individuals who have progressed to the dementia stage as a result of AD, distinguishing them from those in earlier stages of the disease. Results: Precise categorization of Alzheimer’s disease has significant therapeutic importance, as it enables timely identification, tailored treatment strategies, disease monitoring, and prognostic assessment. Conclusion: The stated high accuracy indicates that the suggested vision transformer model has the capacity to assist healthcare providers and researchers in generating well-informed and precise evaluations of individuals with Alzheimer’s disease.

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Abstract Introduction Valproic acid (VPA) is a broad-spectrum antiepileptic drug; but its therapeutic efficacy varies significantly among individuals. The objective of this study is to identify the specific biomarkers that can predict the efficacy of VPA. Methods The GSE143272 dataset from the Gene Expression Omnibus (GEO) was utilized to identify Differentially Expressed Genes (DEGs) between responders and non-responders to VPA. Weighted Gene Co-expression Network Analysis (WGCNA) was employed to identify genes related to the non-responder phenotype. Intersection genes were selected to obtain the core genes affecting VPA tolerance. Lasso regression was applied to determine the core genes that influence the VPA effect. Lasso regression was applied to screen these core genes, using their expression values as independent variables and VPA response as the dependent variable in constructing a univariate logistic regression model. Peripheral blood samples from epileptic patients treated solely with VPA were collected according to nano-discharge standard. The expression levels of target genes were determined by qPCR to validate the accuracy of the model. Results 86 genes were closely related to the response phenotype through WGCNA. 13 intersection genes were obtained by intersection with 97 DEGs, which mainly involve mRNA splicing function and transport pathway. Ultimately, 3 genes-NELL2, SNORD3A and mir-1974 were included in the final model. The Area Under Curve (AUC) for this predictive model was found to be 0.70 (95 % CI: 0.70). qPCR analysis revealed a significant difference in the relative expression of the SNORD3A gene between the responder and non-responder groups. Conclusion Epilepsy patients are at an increased risk of developing drug resistance when undergoing VPA monotherapy. The risk prediction model based on Lasso-Logistic regression demonstrates strong predictive capabilities. The SNORD3A gene may serve as a valuable biomarker for predicting the likelihood of VPA resistance.

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Abstract Background Type 2 Diabetes Mellitus (T2DM) is common worldwide. Patients with T2DM often experience reduced lung function, but the relationship between the two conditions remains uncertain. This study employed Mendelian Randomization (MR) to explore the causal link between T2DM and lung function, and to identify the factors that mediate this relationship. Methods Genome-wide association study data were obtained from public databases. Four glycemic traits were considered exposures, whereas lung function was considered an outcome. Inverse Variance Weighting (IVW) was used to investigate causality, supplemented by MR-Egger and weighted medians methods. Multivariable MR (MVMR) analysis investigated whether T2DM had an independent impact on lung function. Mediation analysis was employed to examine potential mediating impacts. Results IVW revealed that T2DM was associated with decreased forced expiratory volume in 1s (FEV1) (p = 0.012) and Forced Vital Capacity (FVC) (p = 0.004). After adjusting for potential confounders, the effects of T2DM on FEV1 and FVC remained significant. Mediation analysis demonstrated that smoking and Systolic Blood Pressure (SBP) partially mediated the causal relationship between T2DM, and FEV1 and FVC. The proportions mediated by smoking, SBP, and both factors on FEV1 were 0.302, 0.412, and 0.418, respectively, while the proportion mediated by SBP on FVC was 0.594. Conclusions This study validated the causal relationship between T2DM and decreased lung function, with smoking and SBP acting as mediators. This study provides a novel perspective on the occurrence and development mechanisms of reduced lung function as well as potential new targets for metabolic intervention in treatment.

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Abstract Objective Based on the data in clinical studies, the authors explored the potential link between cancer immunotherapy and Neurological Adverse Events (NAEs), and established a clinical picture. Methods The authors searched PubMed, Embase, Cochrane Library, Web of Science databases, and ClinicalTrials.gov for Randomized Controlled Trials (RCTs) using PD-1/PD-L1 inhibitors for cancer until November 2023. A total of 141 articles were included, covering 12 PD-1/PD-L1 inhibitors and 18 cancer types. Results Finally, 90,079 patients of 141 RCTs met the eligibility criteria. Data showed no significant difference in the incidence of NAEs in patients receiving PD-1/PD-L1 inhibitors compared to the control group (OR = 1.07; 95 % CI 0.95, 1.21; p = 0.25). However, the authors surprisingly found that the incidence of serious NAEs in the PD-1/PD-L1 group was higher than the control group (OR = 1.34; 95 % CI 1.24, 1.44; p < 0.00001), the same with NAEs in atezolizumab subgroup (OR = 1.66; 95 % CI 1.08, 2.56; p = 0.02). It is worth noting that the intra-group heterogeneity of the serious NAEs subgroup was relatively small (I2 = 16 %, p = 0.06). Conclusion The authors first proposed the opinion that the incidence of serious NAEs in immunotherapy patients was significantly higher than in other groups, providing a novel direction for research.

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Abstract Background Stomach Adenocarcinoma (STAD) poses a significant burden due to its high prevalence and costly, painful treatments, exerting considerable pressure on individuals. Objectives This study intends to explore novel therapeutic targets to enhance prognosis and alleviate patient stress. Materials and methods Quantitative Real-time Polymerase Chain Reaction was employed to detect MCF2L-AS1 expression in STAD tissues and cell lines. The correlation between this expression and patients' clinical conditions and prognosis was analyzed utilizing the Chi-squared test and Kaplan-Meier method. To investigate the regulatory mechanism of MCF2L-AS1, the Luciferase reporter gene system and transfection experiments were implemented. Cellular behaviors were analyzed through CCK8 and Transwell assays. Results MCF2L-AS1 expression was upregulated in STAD tissues and cells, strongly correlating with TNM stage and lymph node metastases. High MCF2L-AS1 levels were associated with reduced 5-year survival rates compared to the low-expression groups. miR-503-5p, a downstream miRNA, was downregulated in STAD and inversely correlated with MCF2L-AS1. Knockdown of MCF2L-AS1 suppressed miR-503-5p expression, indicating its role as a competitive endogenous RNA. Low miR-503-5p expression reversed the inhibitory effects of MCF2L-AS1 knockdown on STAD cell behaviors. Conclusions The oncogene role of MCF2L-AS1 in STAD is mediated through the negative regulation of miR-503-5p, highlighting its potential as a prognostic marker and therapeutic target.

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Abstract Objective To assess the cognitive and motor effects of an intervention utilizing commercial immersive virtual reality (IVR) games in older adults diagnosed with mild neurocognitive disorder (mild NCD) or mild major neurocognitive disorder and compare these effects with those of a motor-cognitive integrated exercise program. Methods This randomized controlled trial will include volunteers aged 60 years and older diagnosed with mild NCD or mild major NCD. Participants will be randomly assigned to two groups, each undergoing two 45-minute sessions weekly for seven weeks. The Virtual Reality Group (VRG) will engage in six IVR games, while the Exercise Group (EG) will perform integrated motor-cognitive exercises. Outcomes will be measured using the mini-BESTest, Dynamic Gait Index, Box and Block Test, 1-minute sit-to-stand test, Grip Strength Test, Neurocognitive Battery, Word Accentuation Test, Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, Montreal Cognitive Assessment, and Functional Activities Questionnaire. Sample size calculation indicates 32 participants (16 per group) to achieve 80 % power with α = 0.05, accounting for 20 % attrition. The trial is registered at the Brazilian Clinical Trials Registry (RBR-2kk9vnh). Results It is hypothesized that participants in the VRG will demonstrate greater improvements in cognitive and motor performance compared to the EG. Conclusions This study aims to determine whether commercial IVR games can serve as effective cognitive and motor interventions for individuals with mild NCD or mild major NCD.

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Abstract Objectives To evaluate the trends in serum folate test ordering and their abnormal results. Methods The authors retrieved data from an anonymized laboratory database from a single, large, academic hospital from Brazil. The authors retrieved serum folate test results, the number of repetitions and other laboratory measurements obtained in the same time window, ordering setting and clinic. The authors then evaluated the trends in test ordering, and prevalence of low (< 3 ng/dL) results, and assessed targets for improvement in test ordering. Results From January 1st, 2018, to December 31st, 2022, 181,379 folate tests were ordered from 82,052 patients, with 0.7 % of low results, rising from 33,988 in 2018 to 44,187 in 2022. The outpatient setting was the most frequent (89.5 %). The clinics that most frequently ordered folate tests were Gastroenterology (33 %) and Nephrology (9.8 %). Most patients had more than one test ordered (74.8 %). The 135,787 re-tests were performed in 36,300 patients. Many exams were repeated within three (22,570) or six months (46,881). Only 24,243 repetitions were made more than a year after the prior exam. Conclusions Folate test ordering is an increasing trend in this large academic hospital, suggestive of non-clinical guided test ordering and low-value testing.

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Abstract Introduction The importance of the Fibrinogen-to-Albumin Ratio (FAR) as a novel inflammatory and thrombotic biomarker in the development of carotid Intraplaque Neovascularization (IPN) is not well understood. This study aims to investigate the relationship between FAR and carotid IPN characteristics in patients with asymptomatic carotid stenosis. Methods We enrolled patients with carotid plaques for the AngioPLUS examination, and clinical and laboratory indicators were collected. Carotid IPN was evaluated by semi-quantitative visual grading of IPN and Intraplaque Microvascular Flow (IMVF). Binary logistic regression models were performed to determine potential associations between various variables and the presence of high IPN and IMVF. Results In the study, a total of 187 patients were included, with 73 in the high IPN group and 98 in the high IMVF group. The IPN score was positively correlated with the IMVF grade, as indicated by a correlation coefficient of 0.815 (p < 0.001). A FAR value of 7.578 was the optimal cutoff value to differentiate high and low IPN as well as high and low IMVF. After adjusting for various factors, multivariate logistic regression models demonstrated that FAR was a strong predictor of the presence of high IPN and IMVF. Furthermore, a high FAR level was also significantly correlated with the presence of high IPN (OR = 2.81, 95 % CI 1.49‒3.30, p = 0.001) and high IMVF (OR = 2.55, 95 % CI 1.39‒4.68, p = 0.002) when the variable FAR grouping was included in the above models. Conclusion Elevated FAR is closely correlated with the presence of high IPN and IMVF on AngioPLUS and may facilitate plaque vulnerability.

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Abstract Objective To explore the relevant regulation of Plasminogen Activator Urokinase Receptor (PLAUR) by non-coding RNAs (ncRNAs) and the relationship between PLAUR and immune cell infiltration and biomarkers. Methods This is a cross-sectional study. A total of 10 paired primary NSCLC tissues and adjacent noncancerous tissues were collected from Tianjin Medical University General Hospital for RT-qPCR. Clinical data were extracted for RNA sequencing expression data of the PLAUR gene. The authors performed PLAUR’s prognostic value analysis in NSCLC using The Cancer Genome Atlas (TCGA). The authors then identified ncRNAs contributing to PLAUR overexpression by combining analyses of expression, correlation, and survival. Kaplan-Meier curves and log-rank tests were used to evaluate Overall Survival (OS) and Disease-Free Survival (DFS) differences based on PLAUR expression levels. Finally, the relationship between PLAUR and immune cell infiltration, as well as immune cell biomarkers, was analyzed by immune cell infiltration analysis. Results Both the quantitative real-time polymerase chain reaction and the TCGA database results showed significant differences in the expression of PLAUR in NSCLC types. The results showed that patients with a high expression of PLAUR had poorer prognoses, and PLAUR can serve as a prognostic biomarker for patients with NSCLC. The results of studying the regulatory microRNAs (miRNAs) upstream of PLAUR indicated that hsa-miR-340-5p may be the most important regulatory miRNA of PLAUR in NSCLC. Further predictions for upstream long ncRNAs (lncRNAs) in hsa-miR-340-5p indicated that AC008555.6, AC026356.1, TRHDE-AS1, and SNHG14 were the upstream lncRNAs of the has-miR-340-5p/PLAUR axis with the most potential in NSCLC. The expression of PLAUR was significantly correlated with the expression of all immune cells in NSCLC. Conclusion Plasminogen activator urokinase receptor was differently expressed and positively correlated with an unfavorable prognosis in NSCLC. The MIRLET7BHG/hsa-miR-127-3p axis was identified as the most likely upstream ncRNA-related pathway for PLAUR in NSCLC. This study provides insights into the molecular mechanism of action of PLAUR in NSCLC, which may help to develop new drugs to regulate PLAUR expression or its function in tumor development and provide new targets for the treatment of NSCLC.

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Abstract Objectives To evaluate the impact of implementing a structured prioritization process on surgical waiting times and compliance with time-to-intervention targets for non-elective surgeries in a tertiary academic emergency hospital. Methods This observational retrospective single-center cohort study compared two periods before and after implementing a prioritization system. All non-elective surgeries performed from June to August 2022 (pre-intervention) and from November 2022 to January 2023 (post-intervention) were analyzed. The intervention included urgency classification, a real-time Kanban dashboard, and daily multidisciplinary scheduling meetings. The primary outcome was the median time from surgical indication until surgical procedure. The secondary outcome included adherence to predefined acceptable waiting time windows. Statistical comparisons were performed using Chi-Square, Fisher's exact, or Mann-Whitney U tests. A significance level of p < 0.05 was adopted. Results 1851 surgeries were analyzed (967 pre-implementation and 884 post-implementation). The median waiting time was significantly reduced from 17h20min to 8h52min (p < 0.001). Compliance with acceptable waiting time windows increased from 60.5 % to 77.1 % (OR = 2.205; 95 % CI 1.799-2.701). Conclusions Introducing a structured prioritization strategy significantly reduced waiting times and improved adherence to surgical timelines in a high-complexity emergency environment. The model proved feasible, effective, and well-accepted by multidisciplinary teams. The long-term impact of the implementation of the model could be further addressed in future studies.

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Abstract Objective This randomized controlled trial aimed to compare the efficacy and safety of indobufen versus aspirin in reducing Target Vessel Restenosis (TVR) after Drug-Eluting Balloon (DEB) angioplasty in patients with Coronary Artery Disease (CAD). Background Despite advancements in Percutaneous Coronary Intervention (PCI) techniques, TVR remains a significant challenge. Antiplatelet therapy is crucial in managing patients post-PCI, and while aspirin is the standard, indobufen may offer a more favorable safety profile by reducing gastrointestinal adverse reactions. Methods The authors conducted a prospective, single-blind, randomized controlled trial involving patients with CAD undergoing PCI with DEB. Patients were randomly allocated to receive either indobufen 100 mg twice daily or aspirin 100 mg daily, both in conjunction with clopidogrel 75 mg daily, for at least 12-months post-procedure. The primary endpoint was TVR assessed by quantitative coronary angiography at 12-months, while secondary endpoints included Major Adverse Cardiovascular Events (MACE), bleeding complications, and patient-reported outcomes. Results A total of 240 patients were evenly distributed between the indobufen and aspirin groups. No significant differences were observed in the rates of TVR (5.83 % vs. 7.50 %, p = 0.603) and MACE (5.00 % vs. 5.83 %, p = 0.776) between the two groups at one-year post-procedure. Importantly, no significant difference in gastrointestinal bleeding rates was observed between the indobufen and aspirin groups (p = 0.156). Conclusion Indobufen demonstrated non-inferior efficacy to aspirin in preventing TVR and MACE after DEB angioplasty in patients with CAD, with comparable safety profiles and no significant difference in gastrointestinal bleeding rates. However, indobufen is relatively more expensive than aspirin. While the present results suggest that indobufen may be a viable alternative to aspirin, particularly in patients at higher risk of gastrointestinal adverse reactions, this conclusion should be interpreted with caution due to the study's limitations, including its single-blind design and relatively small sample size.

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Abstract Background Antidepressants, a cornerstone of depression treatment, are increasingly scrutinized for their safety concerns. The seizure risk of antidepressants has garnered attention. However, the current research on the relationship between antidepressant use and seizures remains unclear, prompting this study to investigate potential associations using data from the FAERS database. Aim This study sought to assess the correlation between seizures and different antidepressants in individuals without pre-existing epilepsy or neurological comorbidities, as well as to explore potential variations in the occurrence of adverse events linked to each specific antidepressant drug. Methods A disproportionality analysis was conducted to identify potential risk indicators within the FAERS database. Signals were detected using both the Reporting Odds Ratio (ROR) via the frequency approach and the Information Component (IC) through the Bayesian approach. Results A total of 15,940,383 FAERS reports from January 1, 2004, to December 31, 2023, were analyzed. 14 antidepressant drugs were associated with seizures, as defined by 41 preferred terms. Conclusion This study identified 14 antidepressant drugs that showed significant associations with seizures. Bupropion had the highest seizure ROR among the antidepressant drugs evaluated in this study.

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Abstract Objective The aim of this study was to investigate the potential of hsa_circ_0004276 as a diagnostic marker for Postmenopausal Osteoporosis (PMO) and its potential interaction with the RNA-binding protein ELAV-like RNA binding protein-1 (ELAVL1). Methods The circRNA expression profiles obtained from the GSE159121 dataset were used to screen for differentially expressed circRNAs in patients with PMO. hsa_circ_0004276 was further analyzed and validated for its circular structure using a bioinformatics website, actinomycin D, and RNase R assays. Serum samples from 115 PMO patients and 103 healthy controls were collected. RT-qPCR and western blot were applied to assess hsa_circ_0004276 and ELAVL1. The effects of hsa_circ_0004276 and ELAVL1 on osteogenic differentiation of human Bone Marrow Mesenchymal Stem Cells (BMSCs) were investigated by in vitro experiments. Results hsa_circ_0004276 was highly expressed in PMO patients and negatively correlated with low bone mineral density. hsa_circ_0004276 had high specificity and sensitivity for the diagnosis of PMO. hsa_circ_0004276 significantly interacted with ELAVL1. During BMSC osteogenic differentiation, hsa_circ_0004276 knockdown significantly increased calcium deposition and ALP activity, while hsa_circ_0004276 overexpression showed the opposite effect. In addition, ELAVL1 expression was reduced in PMO patients and positively correlated with hsa_circ_0004276. Conclusion hsa_circ_0004276 regulates osteogenic differentiation of BMSCs through its interaction with ELAVL1 in PMO pathogenesis. This finding provides a new perspective for the study of the molecular mechanism of PMO and a theoretical basis for the development of new therapeutic targets.

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Abstract Background Organic foods are often considered healthier and more sustainable, yet healthcare professionals’ understanding and perceptions remain unclear. This study aimed to evaluate their knowledge and perceptions related to organic foods and associated barriers. Methods A cross-sectional survey was conducted among employees at a large hospital in São Paulo, Brazil, between June and July 2024. Using a non-probabilistic convenience sample, an online questionnaire collected sociodemographic data, lifestyle characteristics, and information on participants’ knowledge and perception of organic foods. Descriptive statistics, Chi-Square tests, and logistic regression were applied to identify factors associated with the lack of knowledge. Results A total of 199 questionnaires were completed. Nearly half of the respondents (49.2 %) were not fully aware of what defines organic food. Women represented 80.2 % of the sample. Smoking was significantly associated with a lack of knowledge regarding organic foods. Approximately 30 % were uncertain about cardiovascular risks related to non-organic foods, and cost was identified as a major barrier to consumption. Although most recognized environmental benefits and a potential role in reducing global warming, understanding how organic consumption intersects with human health has remained limited. Adjusted analyses revealed that higher education (without postgraduate training), smoking, and comorbidities were associated with knowledge gaps. Conclusion These findings highlight substantial knowledge gaps among healthcare professionals regarding organic foods.

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Abstract Objective In a prospective, randomized phase II study, exploratory data analysis was conducted to evaluate angiogenesis-associated plasma protein levels in patients with locally advanced cervical cancer Methods Participants were divided into two groups: Group A received neoadjuvant cisplatin and gemcitabine treatment (NAC) followed by chemoradiation with cisplatin and brachytherapy (CRT), while Group B received only CRT. Plasma samples were collected from patients in Group A at three time points: baseline, after NAC, and after CRT. Group B patients had samples taken at two time points: baseline and after CRT. The study analyzed an angiogenesis-associated panel of plasma proteins, including angiopoietin-2, G-CSF, endothelin-1, FGF-1, FGF-2, follistatin, IL-8, HGF, EGF, HB-EGF, PLGF, VEGF-A, VEGF-C, and VEGF- D. Receiver Operating Characteristic (ROC) analyses assessed the predictive value of baseline biomarkers for 12, 24, and 36-month survival outcomes. Additionally, Principal Component Analysis (PCA) was applied to post-CRT biomarker changes to identify coordinated modulation patterns. PCA was based on normalized delta values and eigenvector loadings, enabling identification of biomarkers aligned with Progression-Free Survival (PFS) and Overall Survival (OS). Results Significant differences were observed in the levels of HB-EGF, IL-8, PLGF, and VEGF-C between Groups A and B following CRT. Additionally, angiopoietin-2 levels showed a significant increase in Group B only. NAC treatment in Group A appeared to downregulate IL-8. CRT induced significant changes in HB-EGF, IL-8, PLGF, and VEGF-C levels in both groups. Patients in Group B demonstrated improved PFS and OS compared to those in Group A. Despite these differences in survival outcomes, the authors observed no significant intergroup differences in the tested biomarkers after completion of CRT. ROC analysis of baseline angiogenesis biomarkers demonstrated limited predictive sensitivity for survival outcomes. However, PCA of biomarker changes following CRT highlighted VEGF-A, HB-EGF, and angiopoietin-2 as variables associated with PFS and OS. Conclusion Baseline biomarker levels were not predictive of long-term outcomes. In contrast, CRT alone modulated key angiogenic biomarkers, and post-CRT biomarker changes were associated with improved survival. Such biomarker alterations were not observed following NAC, which was not associated with clinical benefit in this study. These findings underscore the value of dynamic biomarker evaluation and highlight how treatment strategies differentially impact biomarker profiles in advanced cervical cancer.

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Abstract Background Previous studies have indicated that perioperative serum haptoglobin levels are associated with the risk of Acute Kidney Injury (AKI). However, the relationship between haptoglobin and AKI in sepsis patients remains unclear. This study aimed to investigate the association between serum haptoglobin levels and AKI in critically ill sepsis patients. Methods The authors conducted a retrospective cohort study using data extracted from the Medical Information Mart for the Intensive Care (MIMIC) IV database version 3.0. Multivariable logistic regression analysis was used to control for potential confounders. Curve fitting was performed to assess the linearity of the association, and subgroup analyses were conducted to validate the robustness of the findings. Results This study included 1324 participants (mean age 64.7 ± 17.6 years; 53.8 % male). The fully adjusted model showed an inverse association between serum haptoglobin levels and AKI. Each 10 mg/dL increase in haptoglobin decreased AKI odds by 1.4 % (OR = 0.986, 95 % CI 0.973‒0.999, p = 0.037). Patients in the highest haptoglobin group had 34.5 % lower AKI risk versus the lowest group (OR = 0.655, 95 % CI 0.439‒0.976, p = 0.038). The linear relationship (p for non-linearity = 0.152) remained robust in subgroup analyses. Conclusion The present findings suggest that elevated serum haptoglobin levels may serve as a protective factor against AKI in critically ill sepsis patients. Nevertheless, prospective, randomized, controlled studies are required to confirm the findings presented in this investigation.

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Abstract Background and aims Observational studies have indicated a potential association between serum uric acid levels and the risk of intracerebral hemorrhage and subarachnoid hemorrhage. To explore whether this relationship is causal, the authors performed a two-sample Mendelian randomization analysis. Methods and results The authors sourced data on single-nucleotide polymorphisms related to serum uric acid levels from the European Bioinformatics Institute ‒ Association database, along with information on intracerebral hemorrhage and subarachnoid hemorrhage from the same repository. The primary analysis for the Mendelian Randomization was conducted using the inverse variance weighted method, accompanied by sensitivity analyses to validate the findings. The Mendelian Randomization analysis revealed a positive causal association between serum uric acid and the risk of ICH Odds Ratio (OR = 1.29; 95 % CI 1.07-1.54, p = 0.007) and SAH (OR = 1.27; 95 % CI 1.04-1.54, p = 0.018). Conclusion The present research offers direct evidence suggesting that higher serum uric acid levels could raise the risk of Intracerebral Hemorrhage (ICH) and Subarachnoid Hemorrhage (SAH). Additional investigations are needed to explore the mechanisms by which serum uric acid influences these types of hemorrhagic events.

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Abstract Objective Mechanical Ventilation (MV) is a common intervention in Cardiac Intensive Care Units (CICUs); however, its effect on in-hospital mortality remains controversial. This study aimed to investigate the association between MV and in-hospital mortality among patients in the CICU using data from the eICU Collaborative Research Database. Methods Patients were categorized based on whether they received MV, and propensity score matching was applied to adjust for baseline differences. The primary outcome was in-hospital mortality, which was analyzed using logistic regression and sensitivity analyses. Results A total of 12,480 patients in the CICU were included, with 4390 receiving MV and 8090 not receiving MV. In-hospital mortality was notably higher among MV patients (16.0 %) than among those who did not receive MV (4.7 %, p < 0.001). After adjusting for confounding factors, MV remained associated with increased mortality, with an odds ratio of 4.16 (95 % CI 3.40‒5.12) in the matched cohort. Sensitivity analyses confirmed these findings, particularly in patients with acute respiratory failure and shock. Conclusion These results demonstrate that CICU patients receiving MV have a higher mortality risk, underscoring the need for judicious clinical use of MV.

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Abstract Objective This study aimed to assess the extent of Left Atrial (LA) structural and functional reverse remodeling following Radiofrequency Catheter Ablation (RFCA) for Atrial Fibrillation (AF) in patients with persistent AF and Heart Failure with preserved Ejection Fraction (HFpEF). Methods A cohort study was performed following the STROBE Statement. Thirty consecutive HFpEF patients with persistent AF were prospectively enrolled and planned for RFCA. Prior to the procedure, transthoracic echocardiography was performed to assess LA structure, LA strain, and LA contractile function. The same evaluation of LA structure and functional parameters was performed post-ablation at discharge, 1-month, 3-months, 6-months, and 12-months. Baseline data was compared between patients with AF recurrence and non-recurrence post-ablation. Results Among the 30 enrolled patients, 4 patients experienced AF recurrence after 3-months, and 7 were lost to follow-up due to the COVID-19 pandemic. Nineteen patients completed the 12-month follow-up without AF recurrence. Structural reverse remodeling was observed in patients without recurrent AF post-ablation, measured by a significant reduction in LA diameters and volumes. LA reservoir Strain (LASres) showed significant improvement at 1-month follow-up, in parallel with the recovery and improvement in LA contractile Strain (LASct). Greater improvement in LA contractile function evaluated via echocardiographic LA imaging parameters was seen in patients who maintained sinus rhythm following ablation. Conclusion In patients with persistent AF and HFpEF, RFCA for AF with resultant preservation of sinus rhythm results in the reversal of LA morphological remodeling and notable improvements in LA reservoir and contractile function.

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Abstract Background Research has shown that long noncoding RNAs (lncRNAs) play a role in Idiopathic Pulmonary Fibrosis (IPF), but their specific functions and patterns of expression are still unclear. Method A diagnostic study was conducted by utilizing analysis techniques. RNA sequencing (RNA-seq) data from 12 IPF patients and 5 controls was used to study lncRNA functions in IPF. The authors identified Differentially Expressed lncRNAs (DElncRNAs) and explored co-expression networks in a transient manner, as well as using Weighted Gene Co-expression Network Analysis (WGCNA) to identify modules associated with IPF. Results The study found 541 differentially expressed lncRNAs in IPF, with 201 up-regulated and 340 down-regulated. DElncRNAs, especially the up-regulated, were significantly correlated with DEmRNAs at their expression levels. DEmRNAs showed extracellular matrix-related biological functions in addition to increased lncRNAs. WGCNA results demonstrated that Module Eigengene green (MEgreen) and MEred modules indicated the highest negative correlation significance with IPF phenotype, and eigengene patterns of both modules were downregulated in IPF samples. The authors identified six significant lncRNAs in these two modules, including FAM13A-AS1, RP11-180C16.1, MYO16-AS1, AC007278.2, BACH1-IT2, and RP11-153M7.5, and their co-expressed DE mRNAs were enriched in inflammatory response pathways. The authors used single-cell RNA sequencing (scRNA-seq) data to investigate dysregulated lncRNAs and their co-expressed mRNAs. The authors found that five DEmRNAs that were co-expressed with DElncRNAs exhibited dysregulated expression patterns in multiple cell types of the IPF samples. Conclusion LncRNAs are functionally active and potentially involved in the inflammatory response in pathological processes of IPF. It is also important to consider some specific lncRNAs as potential diagnostic biomarkers or therapeutic targets for preclinical and clinical studies with IPF in the future.

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Abstract Background Lung cancer is a leading cause of cancer deaths worldwide, underscoring the need for new biomarkers. Circular RNAs (circRNAs) exhibit potential as biomarkers for lung cancer. ZBTB46 is linked to lung cancer prognosis. This study intends to investigate circRNA expression and the role of ZBTB46 in predicting and treating lung cancer. Methods CircRNAs demonstrate differential expression in lung cancer and paracarcinoma tissues, as identified by high-throughput sequencing (RNA-seq). DEcircRNAs were analyzed through GO and KEGG analyses. A potential circRNA-miRNA-mRNA axis was predicted based on ceRNA theory. ZBTB46 expression in lung cancer tissue was compared to normal tissue. Using the TCGA database, protein expression was compared through the CPTAC and HPA databases. Results We identified 411 differentially expressed circRNAs, of which 365 were down-regulated and 46 were up-regulated. By combining qRT-PCR validation results, ceRNA theory, and intersecting data from several databases, hsa_circ_0002872/hsa-miR-29b-1-5p/ZBTB46 was predicted as the most promising downstream regulatory axis. ZBTB46 mRNA and protein expression were reduced in human lung cancer tissue compared to normal tissue. Conclusions hsa_circ_0002872/hsa-miR-29b-1-5p/ZBTB46 represents an axis that may influence lung cancer progression, with the molecule ZBTB46 potentially inhibiting lung cancer progression and serving as a useful prognostic indicator.

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Abstract Objective To evaluate the effectiveness of AI-based chest Computed Tomography (CT) in a Multidisciplinary Diagnosis and Treatment (MDT) model for differentiating benign and malignant pulmonary nodules. Methods This retrospective study screened a total of 87 patients with pulmonary nodules who were treated between January 2019 and December 2020 at Binzhou People's Hospital, Qingdao Municipal Hospital, and Laiwu People's Hospital. AI analysis, MDT consultation, and a combined diagnostic approach were assessed using postoperative pathology as the reference standard. Results Among 87 nodules, 69 (79.31 %) were malignant, and 18 (20.69 %) were benign. AI analysis showed moderate agreement with pathology (κ = 0.637, p < 0.05), while MDT and the combined approach demonstrated higher consistency (κ = 0.847, 0.888, p < 0.05). Sensitivity and specificity were as follows: AI (89.86 %, 77.78 %, AUC = 0.838), MDT (100 %, 77.78 %, AUC = 0.889), and the combined approach (100 %, 83.33 %, AUC = 0.917). The accuracy of the combined method (96.55 %) was superior to MDT (95.40 %) and AI alone (87.36 %) (p < 0.05). Conclusion AI-based chest CT combined with MDT may improve diagnostic accuracy and shows potential for broader clinical application.

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Abstract Background Acute viral bronchiolitis is the most common lower respiratory tract infection in infants < 2-years of age. Airway Clearance Techniques (ACTs) aim to reduce airway obstruction, thereby decreasing airway resistance, improving gas exchange, and reducing respiratory load, all of which can lead to improved clinical stability. Methods One hundred ninety-two infants were randomly allocated to one of the following ACTs using flow-based techniques: Assisted Autogenic Drainage (AAD; n = 62), Prolonged Slow Expiration (PSE; n = 63), or a control group (n = 67). The sessions were performed in an outpatient setting, with a duration of 20 min and repeated 48 h later. The outcome measures were the Acute Bronchiolitis Severity Scale (ABSS), Bronchiolitis Score of Sant Joan de Déu (BROSJOD), and peripheral oxygen saturation (SpO2) recorded immediately after each intervention. Results Both airway clearance techniques, PSE and AAD, demonstrated significant improvements in clinical severity scores (ABSS and BROSJOD) and SpO2 levels compared to the control group, with PSE showing the most pronounced effects. ABSS (ATSboot p = 0.001; η2 p = 0.105) and BROSJOD (ATSboot p = 0.003; η2 p=0.037) significantly differed and interacted with time, decreasing from baseline to 48 h post-treatment. PSE outperformed the controls in reducing ABSS (p < 0.001; Hedges' g = 1.4 vs. g = 0.37). ACTs improved ABSS and BROSJOD scores compared to controls, with PSE showing the greatest SpO2 increase and wheezing reduction at 20 minutes and one hour post-baseline. At 48 h, the AAD and PSE groups had greater ABSS changes than the controls and fewer retractions at 20 min post-baseline. The AAD group had a lower heart rate, while the controls had higher respiratory rates, and the PSE group had the lowest heart rate. No significant clinical adverse effects were observed. Conclusions Both ACTs using flow-based techniques significantly reduced ABSS and BROSJOD scores immediately after treatment and 48 h later in non-hospitalized infants with moderate acute viral bronchiolitis than in the control group. However, PSE intervention showed greater effectiveness in reducing ABSS and increasing SpO2 than the control and AAD groups.

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Abstract Objective This study explored the effect of Lactate Metabolism-Related Genes (LMRGs) in the diagnosis and prognosis of Sepsis. Methods 599 LMRGs were gained via the Molecular Signatures and GeneCards databases. Next, the authorssifted out Differently Expressed LMRGs (DE-S-LMRGs) through differential expression analysis, Protein-Protein Interactions (PPI) networks, and Weighted Gene Co-expression Network Analysis (WGCNA). Then, DE-S-LMRGs were subjected to Least-Absolute Shrinkage and Selection Operator (LASSO), gene expression patterns, Receiver Operating Characteristic (ROC), and Kaplan-Meier (K-M) survival analyses for obtaining diagnostic genes. Subsequently, the authorsyielded independent factors via univariate and multivariate COX analyses. The diagnostic genes expression levels, immune cell infiltration, immune checkpoint, Human Leukocyte Antigen (HLA) molecules, and K-M survival curves between the clusters were compared. Finally, the authorsapplied quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) for verifying the expression of diagnostic genes in the light of normal and Sepsis samples. Results Four diagnostic genes (APRT, ARG1, UMPS, and LDHB) were identified, which were mainly concentrated in energy metabolism-related functions and immune-related pathways. In addition, age and ARG1 were selected as independent prognostic factors. The two clusters of GSE65682 datasets show significant differences in the expression, immune cells, immune checkpoints, HLA molecules, and survivability of the four diagnostic genes. qRT-PCR revealed that the expression levels of four diagnostic genes were congruent with the results of bioinformatics analysis. Conclusion APRT, ARG1, UMPS, and LDHB might be new ideas for studies related to the diagnosis and treatment of Sepsis.

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Abstract Background The Systemic Immune-Inflammation Index (SII) is widely studied for its role in evaluating Cardiovascular Disease (CVD) and mortality. However, its association with all-cause and CVD mortality in non-elderly diabetic adults remains unclear. This study aims to explore the relationship between SII and both all-cause and CVD mortality in non-elderly diabetic adults in the United States. Methods Cox proportional hazards models and subgroup analyses were used to assess the link between SII and mortality. Restricted Cubic Splines (RCS) examined the nonlinear association between SII and mortality. Results Data from 4680 participants in NHANES (2001‒2018) were analyzed. Over an average follow-up of 98.3 months, there were 625 all-cause deaths and 162 CVD-related deaths. Participants were categorized into two SII groups (higher: > 947.625, lower: ≤ 947.625). Multivariable-adjusted models showed that higher SII levels were significantly associated with an increased risk of both CVD mortality (HR = 3.05; 95 % CI 1.85, 5.01) and all-cause mortality (HR = 1.97; 95 % CI 1.50, 2.58). Subgroup analyses confirmed the consistency of these associations. RCS analysis revealed a nonlinear relationship between SII and all-cause mortality, while the association with CVD mortality was linear. Conclusion Higher SII levels in non-elderly diabetic adults in the U.S. are linked to an increased risk of both CVD and all-cause mortality.

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Abstract Background While Transcatheter Aortic Valve Replacement (TAVR) is increasingly performed in patients with severe aortic stenosis, the impact of Hematologic Malignancies (HM) on associated outcomes, remains unclear. The authors The authors used a contemporary national database to investigate whether HM is associated with adverse clinical and financial outcomes following elective TAVR. Materials and methods The authors The authors identified all adult (≥ 18-years) hospitalizations for elective TAVR in the 2016-2021 Nationwide Readmissions Database. Multivariable models were constructed to evaluate the association of HM with in-hospital mortality, major complications, non-home discharge, Length of Stay (LOS), index hospitalization costs, and 30-/90-day non-elective readmissions. Results Of an estimated 336,998 TAVR procedures, 6123 (1.8 %) involved patients with HM. After risk adjustment, HM was not linked to in-hospital mortality (AOR = 0.96; 95 % CI 0.65-1.40; p = 0.82) or major complications, but conferred a modestly prolonged LOS (β+0.12 days; 95 % CI 0.01-0.25; p = 0.04) and increased costs (β+$1300; 95 % CI $400-$2300; p = 0.01). Moreover, HM was associated with higher odds of 30-day (AOR = 1.27; 95 % CI 1.13-1.42; p < 0.001) and 90-day (AOR = 1.33; 95 % CI 1.20-1.48; p < 0.001) non-elective readmissions. Notably, among 217 HM patients with a history of stem cell transplantation, in-hospital mortality risk was substantially elevated (AOR = 7.7; 95 % CI 1.53-38.8; p = 0.01). Conclusion In conclusion, although HM did not adversely impact in-hospital mortality or major complications following TAVR, it was linked to modestly increased resource utilization and readmission. Patients with prior stem cell transplantation represent a particularly vulnerable subgroup, underscoring the need for multidisciplinary pre-operative evaluation and specialized perioperative care pathways.

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Abstract Introduction Traffic accidents pose a significant public health concern, particularly for motorcyclists, who are especially susceptible to severe and debilitating injuries. These injuries can impair work activities and diminish the overall quality of life. Objective This study aims to assess the functionality, quality of life, and return-to-work status of patients who sustained lower limb fractures due to traffic accidents. Methods The authors conducted a retrospective observational study involving patients hospitalized with lower limb fractures due to traffic accidents at the Institute of Orthopedics and Traumatology at the Hospital das Clínicas, Faculty of Medicine, University of São Paulo, from 2018 to 2022. The authors performed the Timed Up and Go (TUG) test, and the 10-meter walk test, and administered the SF-12 questionnaire to evaluate quality of life. Additional questions regarding their return to work were also included. Results A total of thirty-nine patients were evaluated six months or more following their last surgery. The results indicated that the average TUG time was 12.3 ± 3.3 seconds, and the average speed in the 10-meter walk test was 1.6 ± 0.3 m/s. The SF-12 results revealed a mean score of 48.6 ± 10.9 points in the mental domain and 39.9 ± 9.5 points in the physical domain. Notably, 72 % of patients had not returned to work. The length of hospital stay and the severity of injuries were significant factors influencing patient recovery. Conclusion Although patients demonstrated normal functional status, the majority reported difficulties in performing daily activities and experienced low quality of life even after rehabilitation. This highlights the considerable impact that traffic accidents have on individuals' lives.

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Abstract Background It is unclear to what extent the cardiac cycle influences carotid intima-media thickness CIMT values, especially in individuals with major Cardiovascular Risk Factors (CVRF). The authors analyzed CIMT variability across the cardiac cycle using baseline data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Methods The authors analyzed data from 9546 ELSA-Brasil participants, aged 35 to 74 in six Brazilian cities. CIMT image acquisition was ECG-gated during three cardiac cycles (70 to 90 frames). The authors calculated the Coefficient of Variation (CV), range, and interquartile range to assess variability using frame-by-frame data. In addition, the authors stratified the sample according to the presence of five major CVRFs: hypertension, diabetes, dyslipidemia, smoking, and family history of premature CVD. Results The mean age of the sample is 51.5 years (56% women). CIMT variability was higher in individuals with major CVRF, except for a family history of premature CVD. As expected, variability was higher in measurements of the near wall (CV: 5.8% and 4.9% for left and right CCA, respectively) than those of the far wall (CV: 2.1% for both CCA). A significant positive trend was observed between variability measurements and the number of major CVRFs (all p < 0.001). Discussion The authors found a significant CIMT variability across the cardiac cycle in a very large sample. The magnitude of this phenomenon is more important among individuals with CVRFs. CIMT acquisition protocols must consider the effect of the cardiac cycle to improve risk estimation and reproducibility.

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Abstract Background This Cross-sectional study with 516 elderly individuals aimed to measure the prevalence of Low Back Pain (LBP) at different periods and identify associated factors in the elderly population from Barra Mansa, Rio de Janeiro. Methods A questionnaire on the prevalence of LBP was applied, covering three periods: at the time of the interview, in the last year, and at some point in life, with sociodemographic, clinical, behavioral, and occupational variables in addition, the Numerical Pain Scale and the Roland Morris questionnaire. The significance level established was 5 %. Results The prevalence of LBP was high at the time of the interview, 52.1 % (95 % CI 0.467‒0.575), 93 % in the last year (95 % CI 0.899‒0.954), and 77.4 % at some point in life (95 % CI 0.710‒0.800). The intensity of pain and functional incapacity were considered moderate. The LBP was associated with lower body mass index, female sex, high blood pressure, greater functional disability and perception of regular health. More active elderly people had less LBP, while the white race had a higher prevalence, and emotional problems had impacted severely at the time of the interview. Diabetes mellitus and being widowed were associated with a greater prevalence of LBP at some point in life. Greater functional disability worsened LBP at the time of the interview, while lower disability increased the prevalence of LBP at some point in life. Greater pain intensity was associated to higher LBP in the last year. Conclusion The findings indicate a high prevalence of LBP in different periods associated with sociodemographic, clinical and behavioral factors.

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Abstract Introduction Long-term Familial Adenomatous Polyposis (FAP) outcomes depend on timely diagnosis and treatment. Purpose To analyse the experience in FAP management over a 40-year period. Material and methods Charts from FAP patients (1982‒2023 were reviewed. Demographic data and surgical outcomes were compared between an early (1982 to 2006) and a recent period (2007 to 2023). Results 176 FAP patients were identified. Mean age at treatment (35.6 vs. 29.7), at diagnosis (35.6 vs. 29.7), and younger than 30-years (30.6 % vs. 50 %) showed that most patients were diagnosed earlier in the recent period. The authors detected a reduction of asymptomatic patients (93.5 % vs. 59.5 %, p = 0.0001) and symptoms duration (21.5 vs. 10.6 months, p = 0.0001). Simultaneously, both polyposis diagnoses were motivated by family clustering (26.1 % to 57.1 %, p = 0.02) and not associated with CRC (40.2 % to 67.8 %, p = 0.003) increased. Global CRC incidence decreased from 59.7 % to 32.1 % (p = 0.003). Gradually, pouch surgery (69 %) and the laparoscopic approach (92.7 %) turned out to be the most frequent surgical choices. Long-term mortality also diminished (19.5 % to 9.5 %) mainly due to fewer deaths resulting from CRC (11.9 % to 4.8 %). Diagnosis of desmoid disease (9.8 % to 22.6 %) and duodenal cancer (8.7 % to 2.4 %) changed differently. Conclusions Comparison of outcomes during a 40-year period revealed a clear improvement in FAP management. This scenario resulted from 1) Continuous orientation to family members to advise an earlier diagnosis; 2) Prophylactic surgical treatment with reduced CRC association, and 3) Increased use of laparoscopic techniques with less morbidity and better outcomes.

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Abstract Objective Skin cancer is widely recognized as one of the most perilous diseases on a global scale. Early identification of skin lesions can significantly enhance the treatment effects by aiding in clinical decision-making, hence mitigating the risk of disease progression and metastasis. Unfortunately, the skin images used for training are usually limited and imbalanced. Methods To tackle the aforementioned challenges, a considerable number of deep learning models have been introduced for distinguishing skin cancer. And promising findings have been achieved by these algorithms. Nevertheless, the cross-domain adaptability and resilience of these models remain unresolved for actual clinical applications. One limitation of convolutional neural network-based deep models is their difficulty in finding the embeddings of global relationships for an image. This issue arises from the restricted receptive field of the convolutional operator, which primarily focuses on local information. To address this disparity, the present work introduces an innovative approach based on a vision transformer, with the aim of achieving skin cancer categorization. The presented model leverages the attention mechanism. Furthermore, transfer learning is employed to enhance the weighting parameters of the proposed model. Results Experimental results show the superior performance of the proposed approach compared to traditional approaches, indicating the efficacy of the proposed vision transformer architecture. Conclusions The promising results demonstrate that the proposed approach is a potentially valuable instrument for skin cancer identification.

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Abstract Objective To investigate the effects of Bifid Triple Viable (BTV) capsule on inflammatory factors and intestinal barrier function in children with abdominal infection. Methods 100 children with abdominal infections were selected. The control group (50 cases) was given conventional treatment, and the observation group (50 cases) was given BTV capsule treatment on the basis of the control group. The remission of clinical symptoms was compared, and the changes in inflammatory factors, intestinal mucosal barrier function indices, intestinal flora number, and immune function indices were observed, and the occurrence of adverse reactions during treatment was statistically analyzed. Results The time of vomiting remission, fever remission, stool recovery, and abdominal pain remission in the observation group was shorter than those in the control group. IL-6, CRP, and TNF-α in the observation group were lower and IFN-γ was higher compared with the control group. DAO, D-lactic acid, LPS, Occludin, and ZO-1 in the observation group were lower than those in the control group. The quantity of bifidobacterium, acidobacteria, and clostridium leptum in the observation group was higher than that in the control group, and the quantity of enteric bacillus and enterococcus was lower. IgA and IgG levels in the observation group were lower than those in the control group after treatment. Conclusion BTV capsule can reduce the local inflammatory response of abdominal infection and improve the intestinal mucosal barrier function and immune function.

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Abstract Objectives The mechanisms following glycemic control after RYGB are still not fully elucidated. The objective of the present study was to compare the effects of similar weight loss induced by a Very Low Calorie Diet (VLCD) and by Roux-en-Y Gastric Bypass (RYGB) on the glycemic and gut hormone profile in patients with severe obesity and T2DM. Methods A prospective controlled observational study with 10 patients evaluated before (pre-0), after 10 % weight loss induced by VLCD (pre-1), and after 10 % weight loss induced by RYGB (post). Oral Glucose Tolerance Test (OGTT) was performed in pre-0 and pre-1. In all periods, glycemic (glycemia, insulin) and gut hormone profile (Ghrelin, GIP and GLP1) were evaluated in fasting condition (T0) and 30-, 60-, 90- and 120-minutes after a standard meal (Nutren 1.5®). Results After 10 % weight loss induced by VLCD 5 patients had remission of T2DM in OGTT. There was a significant increase in ghrelin levels after 10 % weight loss with VLCD (pre-1; p < 0.001). There was no difference in GIP levels. There was a significant increase in GLP1 levels between pre-0 and pre-1 (p < 0.004) at T0 and between pre-1 and post at all times after a standard meal (p = 0.01; p = 0.002; p = 0.002; p = 0.01; p = 0.04). Conclusions 50 % of patients had glycemic control after diet-induced weight loss. After RYGB, all patients had improved glycemic control. The increase of GLP1 after weight loss induced by metabolic surgery is responsible for glycemic control.

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Abstract Background and Aims This multi-center retrospective study evaluated the long-term effects of pioglitazone therapy on liver stiffness, hepatic steatosis, and other non-invasive biomarkers in patients with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). Methods A total of 65 patients from three Brazilian public hospitals treated with pioglitazone at doses of 30‒45 mg/day up to 10-years were retrospectively analyzed. Hepatic parameters, including Vibration-Controlled Transient Elastography (VCTE), Controlled Attenuation Parameter (CAP), and FibroScan-AST score, were evaluated before and after treatment. Patients were stratified into two groups based on treatment duration: 1‒3 years and 4‒10 years. Results Significant reductions in Alanine Aminotransferase (ALT) and Gamma-Glutamyl Transferase (GGT) levels were observed in both treatment groups, indicating improvement in liver enzyme profiles. A significant decrease in CAP levels was observed only in the 4‒10 year group (p = 0.002), suggesting a reduction in liver steatosis. Improvement in FAST™ scores was observed in both groups (1‒3 years, p = 0.042; 4‒10 years, p = 0.012). In logistic regression analysis, dyslipidemia was associated with a non-significant trend toward higher odds of liver stiffness reduction (adjusted OR = 1.92, 95 % CI 0.58‒6.45, p = 0.284). Conclusions These findings highlight both the metabolic and hepatic benefits of long-term pioglitazone therapy. They reinforce its potential as a cost-effective and accessible treatment option for MASLD, particularly in resource-limited settings where newer therapeutic alternatives are unavailable.

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Abstract Introduction Conventional mortality statistics that concentrate only on the underlying cause of death may offer a limited view of the complexity of this condition and not fully capture the true extent of mortality from hepatitis C. Objective To describe and analyze deaths due to chronic hepatitis C (CHC) in Brazil, as both a underlying and multiple cause of death, from 2000 to 2019. Methods This ecological study used data extracted from the Mortality Information System and descriptively analyzed causes of death and sociodemographic variables for the deceased. Results During 2000-2019 there were 33,115 deaths with CHC listed on any line of the death certificate, and 25,390 (76.67 %) with CHC mentioned as the underlying cause. The authors found CHC mortality was underenumerated by 30.42 %, considering that 7725 death certificates mentioned this disease as an associated cause. Of these, liver cancer was reported as the underlying cause of 6510 deaths (84.27 %). When CHC was listed as the underlying cause, illnesses of the digestive tract were often associated with these deaths. The total number of deaths in which CHC was one of the multiple causes listed occurred predominantly in men, white people, aged 60 or over and with 12 or more years of education. Conclusion An under-enumeration of mortality from CHC in Brazil was observed from 2000 to 2019, due to the inadequate classification of causes of death on the death certificates. Reviewing the processes of completing death certificates and coding causes is strongly recommended to obtain a more precise indicator of hepatitis C mortality.

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Abstract Objective To identify risk factors and develop a validated nomogram for predicting pneumothorax after CT-guided coaxial biopsy with synchronous Microwave Ablation (MWA) in Ground-Glass Nodules (GGNs). Methods 383 GGN patients were divided into a training set (n = 268) and a validation set (n = 115) in a 7:3 ratio. Univariate and multivariate logistic regression were employed to identify risk factors, followed by the construction of a nomogram model. Receiver Operating Characteristic (ROC) curves and calibration plots were generated to evaluate model performance, with further validation in the independent cohort. Decision curve analysis was applied to assess clinical utility. Results Pneumothorax occurred in 72 cases (26.87 %) in the training set and 32 cases (27.83 %) in the validation set. Multivariate logistic regression revealed that BMI, lesion location, lesion depth, needle diameter, and number of punctures were independent risk factors for pneumothorax (all p < 0.05). Factor importance ranking was as follows: number of punctures > BMI > lesion depth > lesion location > needle diameter. The nomogram demonstrated robust calibration and predictive accuracy, with C-index values of 0.877 (training set) and 0.897 (validation set). The areas under the ROC curve (AUC) were 0.875 (95 % CI: 0.825-0.926) and 0.897 (95 % CI: 0.829-0.965), respectively. Sensitivity and specificity were 0.855/0.813 (training set) and 0.765/0.823 (validation set). Conclusion Key determinants of postprocedural pneumothorax in GGN patients were identified through logistic regression and nomogram modeling. The validated predictive model exhibited excellent discriminative ability and clinical applicability, providing a scientific basis for individualized risk assessment and intervention strategies.

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Abstract Background With frequent new variants of SARS-CoV-2 and vaccine coverage below 50 % in low-income countries, COVID-19 remains a global health challenge, underscoring the need to update evidence-based health strategies and to understand the pandemic from a historical standpoint. Brazil is an important model for study because of the initial widespread infection and subsequent high population adherence to vaccination. Objective To compare severity outcomes in a setting of initial low vaccination and after mass vaccination (> 95 %) according to COVID-19 test positivity. Methods A prospective study with 673 patients tested for COVID-19, followed up until final outcome, in an isolation unit in southern Brazil. We compare the main outcomes and symptoms between the three epidemic waves in Brazil. Results The vaccination coverage was 0.4 %, 35.0 %, and 97.6 % during the three waves, while severe cases decreased significantly from the first to the third. Black and brown ethnicity were more frequent among cases during the second wave, and lower income was associated with the second and third. In the multivariate analysis, higher heart rate and black and brown ethnicity were new factors associated with positive diagnosis and severity independently of period. Conclusions As vaccination progressed, ethnicity and lower income emerged as increasingly important risk factors, uncovering complex relationships between vaccine coverage and access to information in Brazil. The present results offer a broad view of the clinical features of COVID-19 over almost the entire pandemic period and can help evaluate public policies for subsequent management decisions and strategies to reduce health inequities.

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Abstract Introduction Some scales evaluate the self-efficacy of asthmatic adolescents, but do not consider issues related to age and the correct use of medication. Goal To translate to cross-culturally adapt to Portuguese and to test the psychometric properties of the Adolescent Asthma Self-Efficacy Questionnaire (AASEQ). Methods The questionnaire was translated and adapted to Portuguese. The final version was applied in two moments with an interval between seven and fourteen days. Asthma-related Quality of Life Questionnaires (PedsQL and PAQLQA) were also applied. Reliability, agreement, construct validity, ceiling and floor effect, and confirmatory factor analysis were evaluated. Results A total of 135 adolescents (median age 14 (interquartile range 12‒16) were evaluated, and the severity of asthma was mild in 63 (47 %), with controlled symptoms in 90 (67 %). The internal consistency of the AASEQ was adequate (Cronbach's alpha 0.70). The standard error of measurement was very good (SEM = 5.82 points and MDC90 % = 6.68), with moderate reliability (ICC3,1: 0.68 [95 % CI: 0.55-0.77], p < 0.0001. The validity of the AASEQ construct was poor with PedsQL (r = 0.28 and p < 0.05) and PAQLQA (r = 0.27 and p > 0.05). The floor and ceiling effects were adequate. Conclusion AASEQ is a reliable tool to assess self-efficacy in Brazilian adolescents with asthma.

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Abstract Background Endotoxin-induced Acute Lung Injury (ALI) is a severe clinical syndrome with limited treatment. Oxycodone can alleviate the endotoxin-induced ALI, but the exact mechanism remains unclear. The previous study showed that Heme Oxygenase-1 (HO-1) plays a protective role against endotoxin-induced ALI by regulating mitophagy. Thus, the authors aimed to elucidate whether oxycodone attenuates lung injury by regulating mitophagy via the HO-1 pathway. Methods Lipopolysaccharide (LPS) ‒ stimulated mice and Mouse Lung Epithelial (MLE12) cells were used to create the model of ALI. After pre-treatment with Oxycodone for the LPS-induced model in vivo and in vitro, markers of cell and tissue damage, oxidative stress, inflammation, and mitophagy were detected. HO-1 knockout mice and HO-1 siRNA in vitro were used to further clarify the role of Oxycodone. Results Pre-treatment with oxycodone could alleviate lung pathological damage, reduce oxidative stress and inflammatory cytokines, increase the expression of HO-1 while down-regulate the mitophagy-related proteins (PINK1, Parkin, LC3 II/I). Furthermore, treatment with oxycodone in HO-1-knockout mice or HO-1 siRNA-transfected MLE12 cells revealed the protective role of the HO-1 pathway on oxycodone-mediated mitophagy in LPS-induced ALI. Conclusion HO-1 deficiency partially counteracts the beneficial effects of oxycodone on pulmonary protection and inhibition of mitophagy both in vivo and in vitro. Oxycodone pretreatment attenuated LPS-induced systemic inflammation and subsequent lung injury by regulating mitophagy via the HO-1 pathway.

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Abstract Background Inflammation caused by ongoing sepsis stimulation significantly contributes to immunosuppression. However, the alterations in lymphocyte subsets and transcriptome profiles in the development of sepsis-induced acute respiratory distress syndrome (ARDS) remain unclear. Methods Peripheral blood mononuclear cells were collected from patients with sepsis at various points after admission. RNA sequencing was utilized to investigate the transcriptional changes in sepsis patients with and without ARDS. The immune cell composition of patients was dynamically monitored using flow cytometry. The comparisons were made between the changes in T cell subsets in sepsis patients without ARDS and those who developed ARDS during their hospitalization. Furthermore, the authors continuously tracked CD8+ T-cells in sepsis patients who progressed to ARDS. The role of CD8+ T-cells in the worsening of sepsis into ARDS was evaluated. Results There were significant transcriptome gene differences between sepsis patients with and without ARDS. According to KEGG enrichment analysis, most of the differentially expressed genes between these patients were connected to infection, immunological response, cell proliferation, and death. Additional GO enrichment analysis revealed that many genes were linked to T-cell activation, proliferation, and growth. Compared with sepsis patients without ARDS, the number and percentage of lymphocytes, especially CD8+ T-cells, were lower in patients with sepsis-induced ARDS. The recovery of CD8+ T-cells in these patients was slow, too. The results of area analysis under the ROC curve suggested that by the seventh day of hospitalization, sepsis patients with ARDS typically have a CD8+ T-cell count of less than 162.5. Conclusion Sepsis patients with and without ARDS exhibit markedly different genes and immune cells. Patients with ARDS typically exhibited reduced CD8+ T-cell counts and experienced a more protracted recovery process. Monitoring the immune cell composition of sepsis patients regularly and identifying ARDS as soon as possible is critical.

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Abstract Background Acute Myocardial Infarction (AMI) and Heart Failure (HF) are the leading global causes of death from Cardiovascular Diseases (CVD). This study aimed to investigate the association of serum Zinc (Zn), Copper (Cu), and thiol levels with CVD and new potential biomarkers. Methods The study included serum samples from 150 participants, including 50 AMI patients, 50 HF patients, and 50 healthy individuals. Oxidative stress, trace elements (Cu and Zn), and thiol levels were investigated by automated kits in AMI and HF patients compared to the control group. Results T-thiol, N-thiol and Cu levels were higher in the AMI group than in the control group (p < 0.05, p < 0.01, p < 0.01, respectively). Cu and Zn levels were higher in the HF group compared to the control group (p < 0.001, p < 0.01, respectively). Compared to the HF group, T-thiol (p < 0.05), N-thiol (p < 0.05), and Zn (p < 0.001) levels were higher in the AMI group. By ROC analysis, Zn, Cu and thiol levels showed moderate discriminative power, emphasizing their candidacy as biomarkers. Conclusions Despite the limitations of age-related variations and sample size, this study pioneers the comparative analysis of AMI and HF, contributing to the elucidation of the complex connections between Zn, Cu and thiol levels in cardiovascular pathologies. It increases the importance of Zn, Cu and thiol levels in CVD’s status, necessitating further research on this topic with refined methodologies.

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Abstract Objective This study aimed to assess patient and caregiver perceptions following discharge from a hospital transitional care unit in a public university hospital in Brazil. Method: This cross-sectional study collected data through telephone contact using the adapted Brazilian version of the Care Transitions Measure (CTM-15 Brazil). Results The present study showed better results in addressing key patient preferences and challenges in the care plan. The main results indicated that patients with chronic diseases or injuries had higher approval of the transitional care service. The main findings indicated that patients with chronic diseases or injuries had higher approval of the transitional care service. Additionally, a significant correlation was found between age and total score (positive) and age and care plan (negative). Conclusions Hospital transitional care units are crucial for reintegrating patients after hospitalization. Evaluating services with validated scales, like the CTM-15 Brazil, helps identify improvement areas and track outcomes.

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Abstract Objectives Despite the availability of bivalent vaccines targeting both the ancestral SARS-CoV-2 strain and Omicron subvariants, vaccination rates remain low in South Korea. This study aims to evaluate the neutralizing activity against Omicron subvariants following the third SARS-CoV-2 vaccination in patients undergoing chemotherapy, as well as to assess the need for additional vaccinations. Methods Between April and November 2022, the authors assessed the neutralizing activity of the third SARS-CoV-2 vaccine dose in 63 patients undergoing chemotherapy using an ELISA-based surrogate Virus Neutralization Test (sVNT). The authors examined the influence of factors such as prior COVID-19 infection, cancer type (solid vs. hematologic malignancy), type of chemotherapy regimen (cytotoxic chemotherapy, targeted therapy, immune checkpoint inhibitors), and vaccine type (homologous vector, homologous mRNA, heterologous) on neutralizing activity. Results Among the 57 patients included in the analysis, 26 (45.6 %) had a history of SARS-CoV-2 infection. Patients with hematologic cancers exhibited lower neutralizing antibody responses compared to those with solid tumors for Omicron subvariants BA.1 (24.44 % vs. 71.68 %, p = 0.020), BA.2 (48.22 % vs. 94.59 %, p = 0.006), and BA.4/5 (24.76 % vs. 78.06 %, p = 0.046). Among uninfected patients (n = 31), sVNT inhibition scores were significantly lower across all subvariants (e.g., 5.89 % for BA.1 vs. 58.11 % in infected, p = 0.0025). Treatment delays due to infection were observed in 9 patients (17.75 days on average). Although no deaths were directly attributed to infection, one patient died due to disease progression following a treatment delay caused by the infection. Conclusions Patients undergoing chemotherapy displayed weak neutralizing responses against Omicron subvariants, especially those with hematologic cancers or no prior infection. Consequently, it is crucial to actively recommend additional vaccinations with bivalent or newly developed vaccines for these vulnerable patients.

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Abstract Introduction The association between Fibromyalgia (FM) and the FMR1 gene premutation has been suggested, but remains inconclusively established. Previous studies often focus on whether women with FM have the FMR1 premutation, while a more appropriate approach would involve examining FM manifestation in women with the premutation. FM is a condition with multifactorial etiology, and while the rarity of the FMR1 premutation makes it unlikely that most FM cases are linked to this variation, an increased prevalence of FM among premutation carriers is still plausible. The authors present a pilot study with a more effective approach for sample definition that shows a trend toward confirming this association. Objective To investigate the association between FM and the FMR1 premutation, using a study design that focuses on FM occurrence in women with the premutation, rather than the presence of the premutation in women with FM. Method FM occurrence was evaluated in 140 Brazilian women aged 30 to 59, including 70 premutation carriers and 70 controls. Results FM was diagnosed using the 2016 American College of Rheumatology (ACR) criteria. FM frequency was 25.71% among premutation carriers, compared to 12.86% in controls (p = 0.087). Relative risk (RR = 2) analysis showed a higher risk in the premutation group (95% Confidence Interval: 0.965‒4.143, p = 0.0621). Conclusions This study employs a robust methodology with an improved sample definition and consistent diagnostic criteria. However, larger studies are needed to confirm the association and achieve statistical significance; the authors also provide a sample size calculation for future research.

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Abstract Background Endometriosis diagnosis is challenging due to non-specific symptoms that overlap with other gynaecological conditions. This study proposes a non-invasive Machine Learning (ML) ‒ based urine test using Attenuated Total Reflection Fourier Transform Infrared (ATR-FTIR) spectroscopy for rapid, high-throughput screening. Methods A total of 302 symptomatic patients presenting with pelvic pain and MRI referral indications were recruited. After applying exclusion criteria, 100 patients (50 endometriosis-positive, 50 endometriosis-negative with other gynaecological conditions) were included. Urine samples were self-collected during the first visit and analysed via ATR-FTIR spectroscopy. Two Machine Learning (ML) algorithms, sensitivity-tuned and specificity-tuned, were developed using ∼1,700 spectral variables per patient to prioritize either sensitivity or specificity. Results There were no statistically significant differences in patient characteristics between groups, as patients with negative results for endometriosis presented with other gynaecological disorders. The sensitivity-tuned algorithm achieved 93 % sensitivity and 57 % specificity, while the specificity-tuned version reached 93 % specificity but only 27 % sensitivity. Given an endometriosis prevalence of 30 % in symptomatic population, the sensitivity-tuned test reduced unnecessary MRI referrals by 42 %, prioritizing patients most likely to have endometriosis. The analysis time was 40 s per replicate, enabling same-day results. Conclusion This proof-of-concept study demonstrates the clinical potential of a rapid, urine-based ML test to reduce diagnostic delays and imaging costs. Validation in larger, multi-center cohorts is underway to enhance robustness and generalizability.

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Abstract Background Tracheal intubation surgeries are generally challenging procedures compared to other surgeries. Alfentanil is generally used to treat postoperative pain, but it has respiratory depression. The study examined four anesthetic techniques propofol/alfentanil, sevoflurane/alfentanil, propofol/sevoflurane, and propofol/sevoflurane/alfentanil to see if there is an association with a variety of anesthetic parameters for tracheal intubation surgery while maintaining spontaneous breathing. Methods In retrospective analyses, patients received intravenous propofol and bolus alfentanil (PA cohort, n = 105) or exposed to sevoflurane gas and received bolus alfentanil (SA cohort, n = 107) or received intravenous propofol and exposed to sevoflurane gas (PS cohort, n = 109) or received intravenous propofol and bolus alfentanil and exposed to sevoflurane gas (SD cohort, n = 02). Results Patients of the SD cohort achieved the best airway conditions, characterized by faster loss of eyelash reflex and quicker laryngeal mask insertion. However, patients of the SD cohort also exhibited worse hemodynamic stability, shorter operative times, higher postoperative complications, and prolonged hospital stays. Those results were followed for the patients of the PA, PS, and SA cohorts (p < 0.05 for all comparisons). Patients of the SD cohort required fewer numbers of postoperative administrations of a bolus dose of alfentanil than those of patients of the PS, PA, and SA cohorts (p < 0.05 for all comparisons). Conclusions While the propofol-sevoflurane-alfentanil combination improved airway conditions, it caused universal hypotension and frequent bradycardia. Fixed-dose alfentanil (10 µg/kg) without titration may be unsafe in spontaneous breathing protocols due to respiratory depression.

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Abstracts Objective This study aimed to investigate the causal relationship between Telomere Length (TL) and Autoimmune Thyroid Disease (AITD) in Europeans using Mendelian Randomization (MR). Methods Single nucleotide polymorphisms associated with TL and AITD were obtained from genome-wide association studies. MR analysis was conducted using inverse variance weighted as the primary method. Cochran's Q test and leave-one-out sensitivity analysis were employed to assess heterogeneity and robustness, respectively. Results TL was significantly associated with reduced genetic susceptibility to Graves' Disease (GD) in Europeans (Odds Ratio [OR = 0.776], 95 % Confidence Interval [95 %CI 0.625-0.964]; p = 0.022). However, no association was found between TL and Autoimmune Thyroiditis (AIT) (OR = 1.474, 95 % CI 0.870-2.497; p = 0.149). Cochran's Q test and leave-one-out sensitivity analysis confirmed that the findings were free of heterogeneity and robust. Conclusion MR analysis revealed that TL shortening is associated with increased genetic susceptibility to GD in Europeans, but no such association was observed for AIT. Further research is needed to elucidate the mechanisms through which TL influences AITD.

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Abstract Introduction The morphology-based differential diagnosis of Hydatidiform Mole (HM) of the Complete (CHM) and Partial (PHM) types is challenging because of earlier diagnosis of HM owing to the universal application of ultrasound during antenatal care. HMs may present with amplified oncogenes or other gene mutations, resulting in recurrent or neoplastic disease. The cell proliferation markers Ki-67 and HER2 may contribute to the final HM subtype and prognosis. Much is known about the basic mechanisms of HM development; however, other molecular diagnostic and predictive markers need to be investigated. Methods This was an ambispective anatomopathological study of 108 HMs cases. A tissue microarray was used for Ki-67 or HER2 immunostaining analysis. Associations between immunomarker scores and postmolar Gestational Trophoblastic Neoplasia (GTN) were analyzed via Fisher’s exact and linear-by-linear association tests. Results A statistically significant trend toward increased Ki-67 immunostaining in CHM samples was observed. Seventeen HM patients developed GTN, of whom 6 (35 %) had a Ki-67 score of 3+ and 9 (53 %) had Ki-67 score of 2+. Two (12 %) HM patients had a HER2 score of 3+, and 4 (23 %) HM patients had a HER2 score of 2+, of whom 2 (12 %) patients exhibited oncogene amplification by FISH HER2. Discussion Ki-67 and HER2 markers may be useful for the diagnosis and prediction of HM development, providing alternative targeted therapies. This study needs to be interpreted with caution due to its small sample size, high sample exclusion rate, and the absence of significant associations between biomarkers and clinical outcomes.

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Abstract Objective To evaluate the effects of Riociguat treatment in patients with Chronic Thromboembolic Pulmonary Hypertension (CTEPH) at a Brazilian reference center. Methods This observational study was conducted at INCOR-SP and included 8 patients diagnosed with CTEPH between 2016 and 2024 who were treated with Riociguat. Clinical parameters (NYHA functional class, BNP levels, and 6-minute walk distance) and hemodynamic measurements (right atrial pressure, cardiac index, and pulmonary vascular resistance) were assessed pre- and post-treatment, along with risk stratification using COMPERA 2.0. Results The retrospective cohort (mean age 56 ± 17 years; 100 % female) comprised 2 inoperable patients and 6 with residual PH post-PEA. Significant improvements were observed in functional class (p < 0.05), 6-minute walk distance (increased from 398.5 ± 45 m to 413 ± 110 m; p < 0.05), and BNP levels (decreased from 140 ± 191 pg/mL to 28 ± 235 pg/mL; p < 0.05). Additionally, risk stratification according to COMPERA 2.0 improved significantly. However, no significant changes were detected in the hemodynamic parameters (mean pulmonary arterial pressure, right atrial pressure, cardiac index, or pulmonary vascular resistance). Conclusion Riociguat treatment significantly enhanced functional capacity, reduced BNP levels, and improved risk stratification in CTEPH patients, corroborating international evidence. The absence of significant hemodynamic changes underscores the need for larger, prospective studies to fully elucidate the cardiovascular impact of Riociguat. Importantly, the limited availability of Riociguat in Brazil remains a critical challenge that hinders the effective management of CTEPH.

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Abstract Objectives Vascular Cognitive Impairment (VCI) results from reduced cerebral blood flow, leading to cognitive dysfunction. This multicentre randomized controlled trial evaluated the clinical efficacy of acupuncture in improving cognitive function, daily living abilities, and quality of life in patients with Vascular Cognitive Impairment (VCI). In addition to standardized functional assessments, the authors also measured serum levels of BDNF, IL-6, and TNF-α as exploratory biomarkers of neuroplasticity and inflammation. Methods This investigation was designed as a randomized controlled trial, encompassing patients who had been clinically diagnosed with VCI between July 2022 and March 2024. Participants were divided into three distinct groups based on the type of treatment they received. One group was treated with oral donepezil, representing the medicine intervention group. A second group underwent sham acupuncture, serving as the sham acupuncture comparison group. The third group received actual acupuncture treatment, denoting the acupuncture intervention group. The cognitive and functional capabilities of the participants across all three groups were systematically evaluated using comprehensive assessment tools. Results Of the 270 recruited patients, 262 completed treatment and follow-up. Participants received oral donepezil (medicine group), sham acupuncture, or acupuncture. After 4 weeks, all groups showed significant MoCA, MMSE, and ADL score improvements (p < 0.001), with the acupuncture group demonstrating the greatest gains (MoCA: 20.39 ± 3.15 to 25.47 ± 3.14; MMSE: 23.05 ± 2.71 to 27.42 ± 2.57, p < 0.05). These benefits persisted through 12 weeks, while the sham group showed moderate improvements, outperforming the medicine group. SF-36 results indicated significant enhancements in physical, psychological, and social function across all groups (p < 0.001), with the acupuncture group consistently scoring highest (p < 0.05). While improvements in the acupuncture group remained stable, the other groups experienced partial regression. All treatments were well tolerated, with no severe adverse effects. These findings highlight acupuncture’s superior and lasting benefits for cognitive function, daily living, and quality of life in VCI patients. Acupuncture also modulated serum (BDNF ↑) and inflammatory markers (IL-6/TNF-α ↓), suggesting neuroprotective and anti-inflammatory mechanisms. Conclusion Evidence indicates that acupuncture can notably improve cognitive abilities and daily living skills, while presenting few side effects. This research backs the clinical use and endorsement of acupuncture in treating VCI. These findings support the use of acupuncture as an effective and safe intervention for VCI, with sustained functional gains and favorable modulation of peripheral inflammatory and neurotrophic biomarkers.

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Abstract Background: Sarcopenia is a prevalent but underrecognized complication in elderly patients with Type 2 Diabetes Mellitus (T2DM). Its complex etiology limits early diagnosis and intervention. This study developed and internally validated a nomogram for individualized sarcopenia risk assessment in this population. Methods: A cross-sectional study was conducted involving 300 elderly patients diagnosed with T2DM from two tertiary medical centers. Sarcopenia was identified based on the Asian Working Group for Sarcopenia (AWGS) criteria, incorporating both dual-energy X-Ray Absorptiometry (DXA) measurements and handgrip strength assessments. Potential risk predictors were initially filtered using the Least Absolute Shrinkage and Selection Operator (LASSO) method, followed by multivariable logistic regression to ascertain independent factors. A nomogram model was then established integrating these variables. Model performance was assessed through Receiver Operating Characteristic (ROC) curve analysis, calibration plots, and Decision Curve Analysis (DCA) for clinical applicability. Results: Sarcopenia was present in 22 % of participants. Independent predictors included age, sex, glycosylated Hemoglobin (HbA1c), serum albumin, thyroid dysfunction, and physical activity level. The nomogram demonstrated strong predictive accuracy, with an area under the ROC curve of 0.891 in the development cohort and 0.868 in the validation cohort. Calibration and decision curve analyses confirmed its reliability and clinical utility. Conclusions: The proposed nomogram enables early identification of sarcopenia risk in elderly patients with T2DM, supporting personalized intervention strategies. Prospective validation in diverse populations is warranted to enhance its generalizability.

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Abstract Objective Ferritin is independently associated with oxidized Low-Density Lipoprotein (LDL). While high LDL levels are known independent risk factors for cardiovascular diseases, few studies have investigated the relationship between serum ferritin levels and long-term outcomes in CAD patients. Methods A prospective cohort study of CAD participants was performed in Xinjiang Medical University Affiliated First Hospital from December 2016 to October 2021. 1089 CAD patients were divided into two groups according to baseline serum ferritin concentration (ferritin < 160, n = 715 and ferritin ≥ 160, n = 374). The authors investigated long-term mortality as the primary endpoint, including All-Cause Mortality (ACM) and Cardiac Mortality (CM). The longest follow-up duration was 60 months. Results In this study, a total of 17 ACMs, 12 CMs, 34 MACEs, and 41 MACCEs were recorded. There were significant differences between the two groups in the incidence of ACM (p = 0.002) and CM (p = 0.019). After controlling for covariates, multivariate Cox regression analysis showed that ferritin was an independent predictor ACM (Hazard Ratio [HR = 2.674], 95 % Confidence Interval [95 % CI 1.197‒5.971], p = 0.016) in CAD patients. Conclusions High ferritin levels are strongly associated with a higher risk of ACM in CAD patients.

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Abstract Objective This study investigated the cardiopulmonary function of prepubertal patients with Kawasaki Disease (KD) and compared it with that of healthy controls. Study design Retrospective cohort study Methods Data were collected from two medical centers in Taiwan from January 2014 to December 2023. Patients aged 8 to 12 years with a KD history were recruited. All patients and controls (age-, sex-, and body mass index -matched) underwent Cardiopulmonary Exercise Test (CPET) and pulmonary function test. Results A total of 117 KD patients (mean age 9.64 ± 1.66 years; 68 males (58.1 %); (Body Mass Index [BMI] 19.21 ± 4.20 kg/m2) and 121 controls (mean age 9.72 ± 1.66 years; 71 males (58.7 %); BMI 18.47 ± 3.30 kg/m2) were analyzed. The average time from illness onset to enrollment was 7.94 ± 2.84 years. No significant differences in demographic characteristics or pulmonary function were observed. However, the KD group exhibited lower aerobic capacity (24.32 ± 5.02 vs. 26.08 ± 4.89 mL/min/kg, p < 0.001) and peak exercise tolerance (35.43 ± 7.31 vs. 38.48 ± 6.24 mL/min/kg, p < 0.001) compared to controls. Furthermore, the KD group had lower cardiopulmonary function than the control group among males, whereas the difference in females did not reach statistical significance. Conclusions Prepubertal individuals with a KD history demonstrated lower aerobic capacity and peak exercise tolerance than healthy peers, particularly among males. Despite this, they can safely engage in moderate-to-vigorous physical activities, which are essential for maintaining cardiopulmonary health in later life. Encouraging regular exercise among these patients is crucial.

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Abstract Objective The readmission rate of critically ill Heart Failure (HF) patients remains high during the vulnerable phase. However, predictive models based on more comprehensive comorbidities and medication histories are lacking. This study aims to extract these factors to develop interpretable models for predicting readmission risk. Methods The authors recruited critically ill HF patients from the MIMIC-IV database (as training and internal validation cohorts) as well as from the MIMIC-III database (as external validation cohorts). Four models, including Neural Multitasking Logistic Regression (NMTLR) were constructed and evaluated. Furthermore, Shapley Additive Explanations (SHAP) interpreted feature importance, simplifying the optimal model based on variable importance. Results A total of 12,126 patients were included in this study. Among four predictive models, the NMTLR model demonstrated the best predictive performance with the Area Under the Curve (AUC) of 0.752 (internal) and 0.785 (external), with the C-index of 0.7408 (internal) and 0.7724 (external), and with the mean cumulative/dynamic Area Under the Curve (mean AUC) score of 0.747 (internal) and 0.763 (external). Moreover, the Integrated Brier Score (IBS) of the NMTLR model was 0.062 (internal) and 0.043 (external). The SHAP analysis showed over one-third of the top 20 features in the NMTLR model were comorbidities and medications, including a newly relevant drug named psychoanaleptics. Furthermore, the compact NMTLR model also performed well. Conclusion Despite the limited representation of modern HF medications, both the full and compact NMTLR models are useful for predicting HF readmission. Additionally, psychoanaleptics might be a new predictor of readmission, warranting increased clinical attention.

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Abstract Background Sarcopenia contributes significantly to falls, frailty, and functional decline. Falls result from multiple factors. Objectives To assess whether sarcopenia assessment tools can predict falls and recurrent falls in patients with mild to moderate Parkinson’s Disease (PD). Methods The authors conducted a cohort study from March 2021 to March 2023 at a Brazilian tertiary public hospital, including patients aged 50 or older with mild to moderate PD who could stand and walk independently. The authors utilized tests recommended by the revised European consensus on sarcopenia (2019): SARC-F, grip strength, Short Physical Performance Battery, and body composition via DEXA scan. SARC-F is a cost-effective tool for assessing sarcopenia risk, evaluating perceived physical limitations. Participants completed a standardized fall report and were monitored monthly for twelve months. Results Among 103 patients, 48 (46.6 %) experienced falls, and 23 (22.3 %) had recurrent falls, totaling 159 falls. Longer disease duration predicted both falls and recurrent falls over 12-months. A history of falls in the last six months and dysautonomia also predicted falls, while SARC-F scores and type-2 diabetes predicted recurrent falls. SARC-F accuracy ranged from 58.06 % at a score of 4 % to 78.64 % at 10, with a correlation to UPDRS Part III. Conclusions SARC-F, disease duration, and type-2 diabetes were independent predictors of recurrent falls. A history of falls, disease duration, and dysautonomia predicted falls. Confirmed sarcopenia did not predict falls or recurrent falls in this cohort.

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Abstract Purpose The present study aimed to use the C-reactive protein-to-Lymphocyte Ratio (CLR) to investigate the impact of inflammation-immune imbalance on the prognosis of aneurysmal Subarachnoid Hemorrhage (aSAH) patients. Patients and methods A total of 650 eligible aSAH patients were prospectively enrolled in this study. CLR was examined within 24 h after symptom onset and calculated by C-reactive protein levels (mg/L) divided by lymphocyte count (109/L). The main outcome was 3-month unfavorable functional outcomes (modified Rankin Scale score of 4‒6). The secondary outcome was all-cause death (modified Rankin Scale score of 6). Multivariable logistic-regression analysis was performed to explore the relationship between CLR and clinical outcomes. Results Univariate analysis revealed that elevated CLR levels were associated with poor functional outcomes (p = 0.03) and all-cause death (p < 0.01). After adjusting for potential confounding indices, higher CLR levels (> 6.02 mg/109) were significantly associated with increased risk of 3-month poor functional outcomes (adjusted Odds Ratios: 2.89 [95 % CI: 1.02‒8.17]), but not related to all-cause death (adjusted Odds Ratios: 1.46 [95 % CI: 0.56‒3.80]). Conclusions CLR during the hyperacute phase after aSAH might not only be utilized as a reliable biomarker to predict clinical outcomes of aSAH but also provide promising insight into future research to develop tailored treatments targeting inflammation-immune imbalance.

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Abstract Background This study explores potential associations between asthma and the Systemic Immune-Inflammation Index (SII). Methods The study primarily focuses on adults with complete data on SII and asthma from the National Health and Nutrition Examination Survey database (2015-2020). SII is calculated using the formula: platelet count × neutrophil count / lymphocyte count. The connection between SII and asthma was assessed through baseline feature analysis, weighted multivariate regression, subgroup analysis, and smooth curve fitting. Results A total of 13,334 participants were included, with 2045 individuals (15.34 %) having asthma. Subgroup analysis and interaction tests revealed no significant impact of gender, age, body mass index, vitamin C, magnesium, coronary heart disease, or diabetes on the observed association (p for interaction > 0.05). Conclusion Higher SII levels are associated with an increased incidence of asthma. Further prospective studies are needed to confirm these findings.

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Abstract Objective In Brazil — a country of continental dimensions with marked socioeconomic disparities — the use of self-collected samples and first-void urine for cervical cancer screening may be particularly valuable. This study aimed to assess the acceptability of two self-sampling approaches - first-void urine collection and vaginal self-sampling - among women diagnosed with high-grade cervical lesions (CIN2+) referred to a tertiary care center. Additionally, the study evaluated the concordance of high-risk HPV (hrHPV) test results obtained from self-collected samples compared to those collected by a healthcare professional. Methods This cross-sectional study included 100 women. Participants completed a structured questionnaire on clinical history, demographics, gynecological and obstetric background. Following an instructional video, they performed self-collection of urine and vaginal samples. All participants then underwent colposcopic examination for lesion assessment and therapeutic planning. HPV DNA testing was conducted, and agreement analysis was performed between sample types. Results Both urine and vaginal self-collection methods were reported as easy and comfortable. Instructions were considered easy or very easy by nearly all participants for all collection methods. Clinician-collected sampling was associated with higher embarrassment and discomfort. Agreement analysis showed excellent concordance for HPV 16 and other high-risk HPV types between self-collected, urine, and clinician-collected samples, with all comparisons reaching statistical significance. Conclusions Urine and vaginal self-collection are feasible, acceptable, and reliable methods. Urine sampling was the preferred method in the present study. High concordance with clinician-collected samples confirms their clinical utility, and the positive response to instructional videos highlights the importance of educational support.

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Abstract Objectives This study sought to investigate the effect of muscle mass, muscle strength, and physical function on postural balance in Sarcopenia. Methods A total of 1026 subjects aged 60-years and older were screened for sarcopenia and assessed using clinical tests including the Romberg's test, Single Leg Standing Test (SLS), Five Times Sit to Stand Test (FTSST), Timed Up & Go Test (TUGT), and Y-Balance Test (YBT). Results The authors identified distinct predictive patterns: 1) Hand grip strength(muscle strength) emerged as the dominant predictor of static balance performance, while 2) Dynamic balance outcomes were jointly influenced by gait speed (physical function), muscle strength, and age. Notably, dynamic balance demonstrated greater susceptibility to age-related skeletal muscle decline compared to static balance. Conclusion These findings propose clinically actionable pathways: resistance training to target muscle strength deficits for static balance improvement, and combined strength-functional training protocols for dynamic balance rehabilitation in sarcopenia management.

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Abstract Objective This study determined the role of circRNA MALAT1 (circ-MALAT1) in Choroidal Neovascularization (CNV). Methods CNV mice were induced by laser photocoagulation, and Hypoxic human Retinal Microvascular Endothelial Cells (HRMECs) were induced using cobalt chloride. circ-MALAT1 expression pattern was determined in CNV mice and hypoxic HRMECs. Hematoxylin-eosin staining and fluorescein fundus angiography were performed to examine focal areas in CNV mice. Endothelial cell proliferation and migration assay, tubule formation assay, and apoptosis assay were conducted to determine angiogenesis in vitro. Circ-MALAT1-mediated CNV development was investigated using bioinformatics, luciferase analysis, and RNA immunoprecipitation. Results circ-MALAT1 expression was upregulated in laser-induced CNV mice and hypoxic HRMECs. circ-MALAT1 silencing delayed structural disorganization of choroidal membranes and the formation of CNV, which was abolished by miR-96-5p inhibitors. circ-MALAT1 silencing decreased HRMEC viability, proliferation, migration, and tube formation and promoted apoptosis. circ-MALAT1 acted as a miR-96-5p sponge, chelating and inhibiting miR-96-5p activity, which led to increased expression of FOXK2. miR-96-5p overexpression mimicked the anti-angiogenic effects mediated by circ-MALAT1 silencing. FOXK2 overexpression diminished circ-MALAT1 silencing-mediated inhibition of endothelial cell progression. Furthermore, significant upregulation of circ-MALAT1 and FOXK2 expression was detected in clinical samples from neovascular age-related macular degeneration patients. Conclusion The introduction of circ-MALAT1/miR-96-5p/FOXK2 as a potential therapeutic target in this study provides new insights into the molecular pathogenesis of CNV, but our preliminary study only hints at the possibility of this axis as a target for CNV intervention, and its clinical significance still needs to be validated with larger sample sizes.

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Abstract Objective To map studies that assessed the Health Literacy (HL) of people with diabetes, provide a global view of this level of literacy, and investigate its relationship between glycemic target and complication rates. Materials and methods The authors conducted a systematic and sensitive search across the following electronic databases, including publications from inception to August 2021: Embase, LILACS, Cochrane Library, and MEDLINE. Any type of study that assessed any clinical question related to HL in adults with Type 2 Diabetes Mellitus (T2DM) was selected. In the study, participants had to fill out questionnaires that assessed their level of HL with one of the following tools: TOFHLA, S-TOFHLA, NVS, and REALM. Results A total of 57 records were included in this review. The prevalence of inadequate HL ranged between 4.7% and 71.7%. Twenty-six studies evaluated the association between HL and glycemic target, and four investigated the association between HL rates and diabetes complications. Ten of them found an inverse association between HL and glycated hemoglobin, suggesting that inadequate diabetic control was more frequent among patients with lower levels of HL. Conclusions This study found that, apparently, there is a direct relationship between the level of HL and disease control as well as an inverse relationship between HL and the risk of developing some complications. These findings could justify the routine assessment of HL among patients with T2DM, as well as the development of strategies to improve their levels.

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Abstract Background and aims The World Health Organization (WHO) recommends physical activity for a better quality of life (QoL). However, it is unknown if a lesser or an additional physical activity than the WHO recommendation impacts the QoL. The aim of the study was to verify whether people who engage in physical activity above or below the levels recommended by the WHO show differences in quality of life. Methods The International PA Questionnaire (IPAQ) was used to determine the PA characteristics, and the 36-Item Short-Form Health Survey (SF-36) to QoL (SF-36 scores range from 0-100, and a higher score indicates better QoL). A total of 180 men (44.9 ± 14.5 years) were divided into: Group 1 (< 150 min moderate or < 75 min vigorous PA per week); Group 2 (150-600 min of moderate PA or 75-300 min of vigorous PA per week); and Group 3 (> 600 min moderate or > 300 min vigorous PA per week). Results: Group 1 presented significantly lower scores than Group 2 for the overall physical domain (mean difference = 15.5, 95% IC = 22.1 to 8.9, p < 0.001) and overall mental domain (mean difference = 19.1, 95% IC = 27.5 to 10.6, p < 0.001). Group 2 presented similar results to group 3 for the overall physical domain (mean difference = -0.5, 95% IC = 7.1 to -8.2, p = 1.00) and overall mental domain (mean difference = 3.1, 95% IC = 12.9 to -6.6, p =1.00). Conclusion Individuals who comply with the amount of weekly physical activity recommended by the WHO have better QoL (physical and mental) than those who do less physical activity than recommended; however, those who do much more physical activity than the recommended amount do not present additional benefits for QoL.

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Abstract Objective To evaluate temporal and geographical trends of early Neonatal Mortality Rate (NMR) associated with perinatal asphyxia in newborns ≥ 37-weeks’ gestation without congenital anomalies in Brazil, from 2000 to 2020. Method The database was built based on live birth and death certificates, according to the municipality where birth occurred. Perinatal asphyxia was considered if ICD-10 codes were present in any line of the death certificate: intrauterine hypoxia (P20), birth asphyxia (P21) or neonatal aspiration of meconium (P24.0). Prais-Winsten method tested the temporal trend of early NMR associated with perinatal asphyxia per thousand live births. The geographical distribution was analyzed by municipality. Results Over the 21 years, 55,204,633 live births were ≥ 37-weeks’ gestation without congenital anomalies, and 35,443 died with perinatal asphyxia up to day 7 of postnatal life. Early NMR associated with perinatal asphyxia decreased from 0.86 in 2000 to 0.45 in 2020 (annual change: -3.23%; 95% CI: -4.16% to -2.29%). This reduction was observed in all regions of the country, but North and Northeast showed, in 2020, rates above those found in 2000 in Southeast, South, and Midwest. The number of municipalities with early NMR associated with perinatal asphyxia >1.50 in Brazil decreased from 482 vs. 200 in 2000‒2005 vs. 2016‒2020. Conclusion Since 2000, there has been a significant decline in early neonatal mortality rates associated with perinatal asphyxia among infants born at ≥ 37-weeks’ gestation without congenital anomalies in Brazil. However, in 2020, 0.45 per 1,000 of these live births still resulted in death, with marked regional disparities persisting.

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Abstract Objective KAT2A, as a kind of epigenetic enzyme, has been found to be involved in ferroptosis in recent years, so this research is to explore the role and molecular role of KAT2A-mediated modification of histone succinylation by inhibiting ferroptosis and its involvement in asthma. Method An asthma model was established, and the expression of KAT2A, GPX4 and SLC7A11 proteins was analyzed by Western blot and qPCR; Masson staining, TUNEL staining and HE staining were used to observe the pathological changes of lung tissues; The Clone Formation Assay and Cell Counting Kit 8 (CCK-8) were used to assess the cell viability and proliferation; and ELISA was performed for the detection of inflammatory factors; Immune cells were counted with kits. The expression of ferroptosis indicators was evaluated using qPCR and Western blot; ChIP-qPCR was performed to analyze H3K79succ and RNA pol II on the SLC7A11 promoter. Results In vitro assays verified that KAT2A regulates asthma through ferroptosis; in vivo assays verified KAT2A-mediated IL-13 succinylation modification and its effect on asthma; KAT2A controls ferroptosis via SLC7A11 and subsequently regulates asthma; Erastin significantly increased the levels of Fe2+, lipid ROS, SOD, Iron, and MDA, and decreased the expression of GPX4 and SLC7A11 and reduced inflammatory response. Conclusions The authors verified that KAT2A can reduce the inflammatory response caused by asthma, and further clarified that KAT2A-mediated histone succinylation modification participates in the occurrence of asthma by inhibiting ferroptosis, which may become a potential target for asthma treatment.

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ABSTRACT Introduction Asthma-COPD Overlap (ACO) combines characteristics of both asthma and COPD, resulting in fixed airflow obstruction. During the COVID-19 pandemic, these patients may have experienced a decline in quality of life. Objectives To identify demographic, biochemical, and inflammatory markers and their relationship with quality of life during the COVID-19 pandemic in individuals with ACO. Methods This was a cross-sectional study including 174 participants from the ELSA-Brazil study in São Paulo during the COVID-19 pandemic. Participants were allocated into four groups: control (n = 42), asthma (n = 42), Non-Obstructed Smokers (NOS) (n = 38), and ACO (n = 49). Quality of life was assessed using the SF-36 short, CAT, and WHOQOL-bref questionnaires. Complete blood count and C-Reactive Protein (CRP) were analyzed, and serum levels of interleukins IL-4, IL-5, IL-6, IL-8, IL-13, IL-17, and TNF-α were measured using Luminex analysis. Pre- and post-bronchodilator performance of FVC, FEV1, FEV1/FVC ratio, and FEF 25 %‒75 % was evaluated. Correlation analyses were conducted between interleukins and questionnaires, blood count, and spirometry results. Results Quality-of-life questionnaires showed poor mental, physical, and social health during the COVID-19 pandemic, with SF-36 indicating worsened functional capacity in the control and NOS groups, while CAT revealed a moderate impact in the ACO group. The asthma group had elevated IgE levels, and inflammation, as expressed by cytokines (TNF-α, IL-6, IL-8, IL-4, IL-17A, and IL-13), was highest in the NOS group. The ACO and asthma groups showed reduced post-bronchodilator values for FEV1, FEV1/FVC, and FEF 25 %‒75 %. Correlations were found between cytokines and quality of life, lymphocytes, leukocytes, neutrophils, and hemoglobin levels. Conclusion During the pandemic, low quality of life levels were observed in all groups. IgE levels were higher in asthmatics, while the NOS group exhibited greater inflammation. Spirometry indicated lung function impairment in the asthma and ACO groups. Correlations were observed between inflammatory mediators, interleukins, and quality of life.

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Abstract Introduction Fear of Falling (FOF) is a common and natural behavior experienced by most of the elderly population during aging. It is thought to be caused by previous falls, dizziness, depression, and neuromotor impairments. However, the association between FOF and salivary biomarkers such as Cortisol (COR), Testosterone (TT), Dehydroepiandrosterone (DHEA), and alpha-amylase activities has not been consistently explored. Objective To explore the association between FOF and general health status, Functional Fitness (FF), and salivary-related stress biomarkers in institutionalized older women. Materials and method A total of 278 older women were assessed and grouped as having Higher (n = 176) or Lower FOF (n = 102), according to the Falls Efficacy Scale. Saliva samples were collected. Results The Higher FOF group had superior scores in the depressive state and comorbidity scale (p ≤ 0.05). Participants with Lower FOF showed better FF scores. Salivary levels of cortisol were higher, and DHEA levels were lower in the High FOF group (p ≤ 0.05). Spearman's Rank test showed that FOF was inversely correlated with DHEA, alpha-amylase, and FF, whereas COR was directly associated with the FOF scale. Regression analysis indicated that functional fitness indicators were significantly associated with variations in FOF. However, after adjusting for covariates, the influence of physical-functional fitness was reduced, while depressive symptoms and DHEA levels remained statistically significant in the model, suggesting their stronger association with FOF. The observed associations between FOF and biomarkers, especially DHEA, add important evidence to the growing body of literature exploring the multifactorial nature of FOF. These findings contribute to a deeper understanding of the biological components involved and may help inform fall-risk monitoring strategies in institutionalized older populations.

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Abstract Background Myofascial Pain Syndrome (MPS) is regarded as an extremely common clinical disorder, but is not fully understood. Shoulder pain has a lifetime prevalence of up to 66.7% in the general population, and pain due to Myofascial Trigger Points (MTPs) located in the deltoid muscle is fairly common. Analyses of the correlations between innervation patterns and trigger point locations have been successful in other muscular groups. Objective The objective of this study was to provide a mathematical analysis of the entry points of the axillary nerve into the deltoid muscle and correlate them with the described areas of myofascial pain. Method Ten cadavers were carefully dissected to measure a series of parameters in each deltoid muscle. The entry points of the axillary nerve into the deltoid muscle were placed in a cartesian graph created by dividing the deltoid muscle into 4-quadrants. Statistical analysis was carried out on the number of points in each quadrant. Results Quadrant 1 had the largest number of axillary nerve entry sites, with a mean of 6.85 sites (63%), followed by quadrant 3 with 2.75 sites (25%), quadrant 2 with 1.15 sites (10%), and quadrant 4 with 0.25 sites (2%). Conclusion In accordance with the clinical literature, the branches of the axillary nerve in the deltoid muscle corresponded to the described areas of the MTPs. Anatomical correlations between MTPs may be useful tools for gaining a better understanding of the physiopathology of these disorders and providing a basis for their treatment.

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Abstract Background Hepatocellular Carcinoma (HCC) is one of the most prevalent forms of malignancies worldwide, with a low overall survival rate and limited treatments. SESTD1 is upregulated in a variety of cancers and may serve as a potential prognostic indicator and therapeutic target. However, the expression pattern and functional relevance of SESTD1 in HCC are still unknown. Methods SESTD1 expression and its prognostic value in HCC were evaluated by parsing multiple databases, including the Cancer Genome Atlas (TCGA), GEO databases, and Kaplan-Meier (KM) plotter. Gene Ontology (GO) and Gene Set Enrichment Analysis (GSEA) were conducted to investigate the potential biological functions and regulatory pathways of SESTD1. The relationship between SESTD1 expression and immune-infiltration levels was investigated in the Tumor Immune Estimation Resource (TIMER). RT-qPCR and Western blot analysis of tumor tissues were performed to verify SESTD1expression in HCC. CCK8, colony formation, and transwell assays were used to evaluate the influence of SESTD1 on HCC cell proliferation and migration. Results The authors identified significantly elevated SESTD1 expression in Hepatocellular Carcinoma (HCC) tissues, which is associated with poor patient prognosis. Functional enrichment analysis revealed that SESTD1 regulates cell proliferation and the cell cycle, and in vitro experiments validated that silencing SESTD1 suppresses HCC cell proliferation and metastasis. Mechanistically, SESTD1 appears to modulate immune cell infiltration within the tumor microenvironment and shows a positive correlation with the expression of immune checkpoint molecules PD-1 and PD-L1. Conclusion SESTD1 may serve as a diagnostic and prognostic marker, as well as a potential target for immunotherapy in HCC.

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Abstract Introduction The PNPLA3 rs738409 C>G polymorphism has been associated with fibrosis and steatosis in Chronic Hepatitis C (CHC) patients. However, its impact on Hepatocellular Carcinoma (HCC) development in this population remains unclear. This study aimed to evaluate the impact of the PNPLA3 polymorphism on the risk of HCC development in CHC patients in Brazil. Methods This retrospective case-control study included 235 CHC patients with advanced fibrosis, 119 with HCC, and 116 without HCC. The PNPLA3 polymorphism was analyzed using both the dominant and recessive models. Multivariate logistic regression was performed to assess factors independently associated with HCC development. Results The HCC group exhibited a higher proportion of male patients (p < 0.0001), alcohol abuse (p < 0.001), tobacco consumption (p < 0.0001), and ALBI grade 2‒3 (p < 0.001). The PNPLA3 genotype frequencies were CC 45.4%, CG 46.2% and GG 8.4% in the HCC group, and CC 51.7%, CG 40.5% and GG 7.8% in the non-HCC group. No significant differences in genotype frequencies were observed for the dominant model (p = 0.33) or the recessive model (p = 0.92). Gender (p = 0.001), tobacco consumption (p < 0.001), and ALBI score (p = 0.012) were identified as independent factors associated with HCC development. However, the PNPLA3 G allele was not an independent factor associated with HCC risk in either the univariate analysis (OR = 1.15, 95% CI 0.63‒2.08, p = 0.65) or the multivariate analysis (OR = 0.99, 95% CI 0.49‒2.00, p = 0.98). Conclusion The PNPLA3 rs738409 polymorphism was not associated with HCC development in CHC patients with advanced fibrosis in the Brazilian population. Further studies are required to confirm this finding.

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Abstract Purpose Medical education often provides limited exposure to urology, despite the growing prevalence of urological conditions. To address this gap, the Urological Medical Student Interest Group (UMSIG) was established in 2006. This study aimed to evaluate the educational and professional impact of UMSIG participation among its current and former members. Materials and methods An electronic survey was distributed to 226 former and current UMSIG members between December 2023 and February 2024, collecting data on demographics, motivations for joining, perceptions of UMSIG activities, and influence on career decisions. Quantitative data were analyzed using descriptive statistics. Results We received 111 responses (49.1 % response rate). The primary motivations for joining UMSIG included a desire to deepen urology knowledge (77.5 %) and recommendations from peers (56.8 %). Most respondents (71.2 %) reported that UMSIG enhanced their urology education beyond the standard curriculum through practical experiences. Participation also had impact on career trajectories: 52.0 % of non-urologists indicated that UMSIG influenced their current specialty, while 78.6 % of urologists cited it as a decisive factor in their choice of specialization. Overall satisfaction was high, with a median rating of 9/10, and 55.9 % considered UMSIG superior to other medical student interest groups. Conclusion Participation in UMSIG provided a valuable supplement to formal medical education by offering practical clinical experience and research opportunities. The program influenced participants' career decisions, reinforcing interest in urology and related surgical fields. These findings underscore the important role of structured extracurricular programs in medical education, particularly in specialties with limited curricular presence.

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Abstract Lower eyelid malposition, a commonly encountered eyelid disorder, is often linked to discomfort, visual disturbances, and cosmetic concerns. Various treatment modalities have been employed to address these conditions, but their effectiveness and safety remain subjects of debate. This systematic review, aiming to compare and evaluate these treatments, produced a comprehensive analysis of diverse approaches to managing lower eyelid malposition. The search encompassed electronic databases, clinical trial registries, and relevant journals from inception to September 2023. Fifteen studies meeting the inclusion criteria, involving 709 patients (855 eyelids), were reviewed, comprising 12 randomized controlled trials and 3 ongoing trials. We assessed the quality of each included study using the Cochrane Risk-of-Bias tool for randomized trials (RoB v2). We analyzed success rates, recurrence rates, adverse events, and patient satisfaction. Results revealed that modifications to the conventional Lateral Tarsal Strip exhibited high success rates and low recurrence rates. Other treatments, including Everting Sutures, Retraction Pelication, and Orbicularis Muscle Shortening, showed promise in specific cases. Complications, generally mild and manageable, were reported across all modalities, with patients expressing overall satisfaction. The systematic review highlights the effectiveness and safety of various surgical interventions for lower eyelid malposition, offering durable outcomes and minimal recurrence. Tailoring treatments based on patient characteristics and anatomical variations is crucial. Further research is warranted to refine indications for each treatment option in this evolving field.

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Abstract This mini-review explores the potential of precision medicine and personalized nutrition in addressing health challenges faced by perimenopausal women, focusing on the role of genetic polymorphisms in key metabolic pathways. Specifically focus on the single nucleotide polymorphisms (SNPs) in the COMT, FUT2, and MTHFR genes, which influence neurotransmitter metabolism, gut microbiota composition, and folate homeostasis, respectively. These polymorphisms are critical in modulating hormonal fluctuations, metabolic imbalances, and nutrient absorption during perimenopause. The review highlights the impact of COMT rs4680 on stress response and mood disorders, FUT2 rs602662 and rs601338 on vitamin B12 absorption and cortisol metabolism, and MTHFR rs1801133 and rs1801131 on homocysteine levels and cardiovascular risk. Furthermore, the integration of machine learning in precision medicine is discussed, offering insights into how genetic data can optimize personalized interventions. This approach enables targeted nutritional and therapeutic strategies to mitigate the metabolic and psychological effects of perimenopause. Overall, this review underscores the importance of incorporating genetic testing into preventive care for perimenopausal women to enhance quality of life and promote healthy aging.

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Abstract Introduction Autism Spectrum Disorder (ASD) is a neurodevelopment spectrum characterized by persistent deficits in social communication and interpersonal interaction, along with restricted and repetitive patterns of behavior, interest, or activities. The appropriate screening and diagnosis must be realized to improve the children's prognosis. Moreover, appropriate treatments are necessary to promote better social integration and development. In this scenario, this systematic review aims to evaluate the impacts of behavioral therapies applied in healthcare settings for patients with ASD. Methods This systematic review followed the PRISMA guidelines. The databases MEDLINE, Embase, CENTRAL (Cochrane), and Lilacs were accessed, and gray and manual searches were performed. The search strategy was created with terms referring to autism and behavioral therapy. The studies were assessed qualitatively. Results Randomized clinical trials and observational studies demonstrated improvements in cognitive and verbal components of patients who received behavioral therapies in therapeutic settings. These results indicate a positive impact of both cognitive-behavioral therapy and ESDM on the development of patients’ skills. Among the cognitive-behavioral therapies, the one based on the MASSI protocol did not impact the reduction of anxious symptoms. As for cognitive-behavioral therapy, one study demonstrated that the Behavioral Intervention for Anxiety in Children with Autism (BIACA), when compared to the Coping Cat protocol, improves cognition and reduces anxiety symptoms. Despite these results, further randomized clinical trials comparing behavioral therapies with one another are needed. Conclusion In the context of behavioral therapy within a healthcare setting, the Early Start Denver Model (ESDM) showed improvements in the cognitive, verbal, and social aspects of the evaluated patients. Improvement in scores sometimes is achieved independently of the group and related to the time of interventions.

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Highlights Ethnopharmacological knowledge is passed down through generations by women in the community, who use plants especially for sexual and postpartum care.

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Highlights Knowledge was low mainly about contraceptive methods of high effectiveness. The acceptance of the chosen contraceptive method by deaf women was satisfactory. There are no intervention studies to improve contraceptive use among deaf women.

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Highlights Mitochondria regulate cellular functions, and mtDNA mutations can affect metabolism. mtDNA mutations are promising biomarkers for cancer detection and tumor progression. These mutations might influence therapy response, drug resistance, and patient outcomes. Tools and models advance precision oncology and mitochondrial-targeted treatments.

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Highlights NMES+ can improve the aerobic capacity of individuals in functional decline. NMES+ appears to improve physical functional capacity in general. More RCTs are needed to better evaluate the evidence found.

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ABSTRACT Background: Antidepressant-Induced Sexual Dysfunction (AISD) is a significant public health concern, and pharmacological treatments may offer potential solutions for managing this side effect. This study aims to assess the efficacy of these therapies in treating AISD in women, as well as their impact on improving depressive symptoms. Methods: The authors conducted a search of PubMed, Cochrane, Scopus, Web of Science, Embase, and ClinicalTrials.gov databases up to July 3, 2024, including Randomized Controlled Trials (RCTs) comparing pharmacological treatments with placebo. The risk of bias was assessed using the Cochrane Risk of Bias tool (RoB 2.0). Data synthesis was performed with RevMan 5.4, and the certainty of the evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Results: Eleven studies, with 859 women, were included in the review. Two studies were used in the metaanalysis. The participants’ ages ranged from 28 to 48 years. The interventions studied included Aphrodite, bupropion SR, ephedrine, maca root, rosa damascena, saffron, sildenafil, testosterone, and the compound VML-670. Bupropion SR 150 mg/b.i.d. showed improvements in three sexual function domains: desire (1.74 [1.03, 2.44], p = 0.00001), arousal (1.30 [1.16, 1.43], p = 0.00001), and orgasm (1.90 [1.78, 2.02], p = 0.00001) compared to placebo. However, it did not improve depressive symptoms (0.46 [-0.71, 1.63], p = 0.44). The GRADE rating for the evidence quality was low. Conclusions: Bupropion SR 150 mg/b.i.d. is the most effective pharmacological treatment for AISD in women, though the evidence quality is low. Further clinical trials focusing on women with rigorous methodologies are needed to strengthen these findings. PROSPERO registration number: CRD42024496931.

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ABSTRACT Background and aim: Minimally invasive techniques offer alternatives to conventional surgery in the treatment of early-stage colorectal cancer, reducing morbidity. Transanal Endoscopic Microsurgery (TEM) and Transanal Minimally Invasive Surgery (TAMIS) are widely used, while Endoscopic Submucosal Dissection (ESD) is gaining attention for its ability to achieve complete resection with low recurrence rates. This study compares the efficacy and safety of ESD with Transanal Endoscopic Surgery (TES). Methods: The authors performed a systematic review and meta-analysis of comparative studies involving patients with endoscopically resectable rectal lesions. Electronic searches were conducted in MEDLINE, EMBASE, Cochrane, and LILACS. Outcomes included recurrence rate, complete resection, en bloc resection, hospital stay, procedure time, and complication rate. Results: The analysis included ten observational studies and one Randomized Controlled Trial (RCT) involving 1,094 patients. No significant differences were found in terms of recurrence rate, en bloc resection, R0 resection, and complications between techniques. The RCT showed a shorter procedure time in the TES (RD = 16.6; 95 % CI 8.88 to 24.32; p < 0.0001), whereas observational studies found no significant difference. In addition, observational studies found a shorter hospital stay duration in the ESD (MD = −1.22; 95 % CI −2.11 to −0.33; I2 = 82 %; p < 0.007), while the RCT found no difference. Conclusion: ESD and TES are safe and effective for the treatment of early-stage rectal tumors. Rates of local recurrence, block resection, R0 resection, complications, and procedure time were similar. However, the RCT showed a shorter procedure time with TES, while observational studies showed a shorter hospital stay with ESD.

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Abstract Phyllodes Tumor (PT) of the breast is a rare type of fibroepithelial neoplasm, classified into benign, borderline, and malignant subtypes. These tumors are known to be locally aggressive and have an inherent potential for Local Recurrence (LR), even after adequate surgical treatment. Establishing strategies to reduce LR has become increasingly important, as 21 % to 36 % of patients experience disease recurrence despite achieving negative surgical margins. Although surgical resection of the lesion is the gold standard treatment for all subtypes of phyllodes tumors, the ideal extent of the surgical margin remains a topic of debate with no consensus in the literature. Adjuvant radiotherapy is suggested as a tool to improve local control of the disease and reduce the recurrence rate; however, published data on this approach are currently conflicting. In this review paper, the authors will provide a detailed analysis of the current evidence on the diagnosis, treatment, follow-up, outcomes, and future perspectives of phyllodes tumors.

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Abstract A medical error is a preventable adverse effect of medical care. These errors are usually avoidable. They are a vast source of ethical, financial, and even mental problems affecting patients, physicians, and healthcare organizations. The negative impact on patients can be physical, generating sequelae or disability. It could lead to a loss of trust in the patient and his family in the doctor or the hospital where he has been treated. On the other hand, doctors resist disclosing their errors to the patient, fearing lawsuits and financial losses. Disclosure errors are also an imperative moral duty. In this narrative review, the authors discuss obstacles that exist and prevent an adequate open disclosure, including flaws in medical education, and propose ten steps to proceed with an open disclosure if a medical error occurs.

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Abstract Objective This meta-analysis aimed to determine the efficacy of melatonin on mortality in patients with severe-to-critical illness COVID-19. Methods A systematic search was made of PubMed, Embase, Cochrane Library, and clinicaltrials.gov, without language restrictions. Randomized Controlled Trials (RCTs) on the treatment of severe-to-critical COVID-19 with melatonin, compared with placebo or blank, were reviewed. Studies were pooled to Odds Ratios (ORs), with 95 % Confidence Intervals (95 % CIs). Results Three RCTs (enrolling 451 participants) met the inclusion criteria. Melatonin showed a significant effect on in-hospital mortality (OR = 0.19, 95 % CI 0.05 to 0.74; p = 0.02). Conclusions Melatonin significantly reduced in-hospital mortality in patients with severe-to-critical COVID-19. Melatonin should be considered for severe-to-critical COVID-19 patients.

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Abstract Introduction Uterine transplantation is indicated for women with absolute uterine factor infertility, which is usually associated with congenital causes (the most common being Mayer-Rokitansky-Kuster-Hauser syndrome) or acquired via hysterectomy. For these women, uterus transplantation is the only possibility for them to be able to conceive and have a biological child. The aim of this study was to understand the motivations that lead women with absolute uterine factor infertility to wish to undergo a uterus transplant. Methods A systematic literature review was performed in the following databases: Medline (PubMed), Embase, Cochrane (CENTRAL), Scopus, Web of Science, and LILACS. Results 439 articles were identified, and nine studies were finally selected. Uterine transplantation was the preferred choice over adoption and surrogacy in most studies (ranging from 45 % to 97.5 %). The main motivations for this type of transplant include the desire to conceive a pregnancy, the desire to have a genetic child, the desire to have control over pregnancy, the physiological repair of the body, the restoration of femininity, and the desire to contribute to science. Conclusion The motivations for uterus transplantation go far beyond the desire to get pregnant and include personal and unique motivations.

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Abstract Objectives To systematically evaluate the efficacy and superiority of glucocorticoids in the treatment of severe pneumonia. Method Randomized Controlled Trials (RCTs) on glucocorticoids in the treatment of severe pneumonia were retrieved from CNKI, CBM, China Science and Technology Journal Database (VIP), Wanfang Database, and PubMed as of January 1, 2017. The literature was independently and objectively screened, extracted, and evaluated by two researchers, and a meta-analysis of the extracted data was performed using Revman 5.3 software. Results Ten studies that met the inclusion criteria were included, with a cumulative total of 1120 cases. The meta-analysis results confirmed that the observation group was superior to the control group in terms of efficacy rate, temperature recovery time, cough relief time, rale disappearance time, and serum CRP level. There was no statistically significant difference in terms of the incidence of adverse reactions, mortality rate, and reinfection rate between the two groups. Conclusions Glucocorticoids showed an obvious clinical efficacy in patients with severe pneumonia. However, due to the small number of included studies and the ambiguity of numerous bias risk assessments, high-quality and large-sample RCTs are still needed to provide corroborating evidence.

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Abstract Objective To evaluate the comparative outcomes of Minimally Invasive Radical Prostatectomy (MIRP) versus Open Radical Prostatectomy (ORP) to treat localized prostate cancer, using only Randomized Controlled Trials (RCTs) to ensure high-quality evidence. Method A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines, focusing solely on RCTs comparing MIRP (robot-assisted or laparoscopic surgery) and ORP. Literature searches across multiple databases, including Cochrane Library, Medline, Embase, Lilacs, Scopus, Web of Science, NIH, Clinical Trials, and EU Clinical Trials Register, identified studies meeting predefined PICOT criteria. Four RCTs met inclusion criteria ‒ two representing the same cohort of patients ‒ and were analyzed for perioperative, functional, and oncologic outcomes. Quality assessment utilized the ROB-2 tool to gauge the risk of bias. Results Three RCTs encompassing 1051 patients were analyzed. MIRP demonstrated statistically significant benefits over ORP in terms of reduced perioperative blood loss (Standardized Mean Difference [SMD = -3.058], p = 0.006), lower transfusion rates (Odds Ratio [OR = 0.137]; p = 0.009), and fewer overall complications (OR = 0.465; p = 0001). However, no significant differences were found in long-term oncologic and functional outcomes, including urinary continence and erectile function. Positive surgical margins and additional treatments also did not differ significantly between groups. Conclusion This systematic review and meta-analysis of RCTs indicated that MIRP offers perioperative advantages over ORP, supporting its role as a safe and effective option for localized prostate cancer.

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Abstract Objective The growth of ground-glass nodules in the lungs is an independent risk factor for the occurrence of lung cancer, which provides the basic conditions for the occurrence of lung cancer. However, risk factors for the growth of ground-glass nodules in the lungs have not been fully identified. The purpose of this meta-analysis was to assess risk factors for the growth of ground-glass nodules in the lungs. Methods Computerized searches of the electronic databases of PubMed, Web of Science, Cochrane Library and Scopus for published studies on risk factors for the growth of ground-glass nodules in the lungs. The search time limit is from the establishment of the database to March 2024. Two review authors independently searched the studies according to the inclusion and exclusion criteria, and the quality of the selected studies was evaluated using the Newcastle-Ottawa Scale (NOS), and RevMan 5.4 software was used for meta-analysis. This review is registered in the International Prospective Register of Systematic Reviews (PROSPERO) (identifier CRD42024499763). Results Fourteen studies involving 2059 patients were included, and 14 statistically significant risk factors were identified. The results of meta-analysis showed that age (WMD = 4.61, 95 % CI [1.73∼7.49], p = 0.002), female (OR = 0.65, 95 % CI [0.51∼0.82], p = 0.0003), history of smoking (OR = 1.76, 95 % CI [1.07∼2.92], p = 0.03), history of malignancy (OR = 1.53, 95 % CI [1.16∼2.02], p = 0.003), lesion size (≥ 8 mm) (OR = 1.19, 95 % CI [1.12∼1.26], p < 0.00001), air bronchial sign (OR = 6.09, 95 % CI [3∼12.33], p < 0.00001), lobulation sign (OR = 2.3, 95 % CI [1.58∼3.36], p < 0.00001), spiculated sign (OR = 5.56, 95 % CI [1.39∼22.3], p = 0.02), vascular bundle sign [OR = 2.54, 95 % CI [1.85∼3.48], p < 0.00001), initial diameter (≥ 8 mm) (OR = 1.89, 95 % CI [1.34∼2.67], p = 0.0003), vacuolar sign (OR = 2.62, 95 % CI [1.46∼4.69], p = 0.001), solid nodules (OR = 4.6, 95 % CI [1.96∼10.79], p = 0.0005), solid components (OR = 13.77, 95 % CI [7.08∼26.78], p < 0.00001) and nodule roundness (OR = 2.85, 95 % CI [1.19∼6.81], p = 0.02) were risk factors for the growth of ground-glass nodules in the lungs. However, pleural adhesion (p = 0.47) and pleural retraction (p = 0.07) were not statistically significant. Conclusion This systematic review and meta-analysis showed that there are many risk factors for the growth of ground-glass nodules in the lungs, and medical staff should identify the above risk factors as early as possible in clinical work and formulate targeted interventions for precise prevention.

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Abstract Objectives No meta-analysis has been conducted on the relationship between the MCP-1-2518A/G gene polymorphism and tuberculosis susceptibility in the Chinese population. The aim of this study was to investigate whether MCP-1-2518A/G polymorphism is associated with susceptibility to TB in Chinese. Method Publications addressing the association between the MCP-1-2518A/G polymorphism and TB risk were selected from the PubMed, Embase, CNKI and Wanfang databases. Data were extracted from the studies by two independent reviewers. Statistical analysis was performed using RevMan 5.1 and STATA 12 software. Results Ten case-control studies were extracted from 10 articles on polymorphisms involving 1634 TB patients and 1768 controls. The results of the meta-analysis showed that a significantly increased risk for TB was found for Chinese individuals with the polymorphism as follows: dominant model (GG+GA vs. AA Odds Ratio [OR = 1.53], 95 % CI 1.14‒2.07, p = 0.000); recessive model (GG vs. GA+AA Odds Ratio [OR = 1.63], 95 % CI 1.13‒2.35, p = 0.009); and a homozygote comparison (GG vs. AA Odds Ratio [OR = 1.93], 95 % CI 1.19‒3.13, p = 0.008). In the subgroup analysis by ethnicity, significantly elevated risks were found in non-Han Chinese individuals but not in Han Chinese individuals (mutant homozygous GG vs. AA: OR = 3.81, 95 % CI 2.07‒7.00, p = 0.000). Conclusions This meta-analysis suggested that the -2518A/G polymorphism of the MCP-1 gene is a risk factor for TB in Chinese individuals. In the GG vs. AA model, non-Han Chinese individuals had a higher risk of tuberculosis than Han Chinese individuals.

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Abstract Objective To identify the impact of using electromyographic biofeedback on pelvic floor rehabilitation in men with post-prostatectomy urinary incontinence. Materials and methods Searches in the databases were carried out: Pubmed/Medline, Latin American and Caribbean Literature in Health Sciences, Physiotherapy Evidence Database, Cochrane Library, Embase, Scopus, Web of Science, and in gray literature. The study included randomized clinical trials that treated men with post-prostatectomy urinary incontinence using electromyographic biofeedback in pelvic rehabilitation compared to other resources or no treatment. Studies including incontinent men with sphincter implants, pharmacological treatments, or studies with incomplete data were excluded. Assessment of risk of bias using the Critical Appraisal Tool developed by Joanna Briggs Institute for randomized clinical trials and the GRADE approach to assess the certainty of evidence of meta-analysis results were used. Results 16 articles were included, of which, 7 studies were subjected to two meta-analyses to assess the relative risk of men becoming continent and the reduction of urine loss through pad. Participants who received treatment showed a 1.78 times greater risk of achieving continence compared to those who did not receive treatment (RR = 1.78; 95% CI 1.29‒2.45; I2 = 77%). The limitations of the present study are the lack of high-quality evidence, in which existing trials suffered from a lack of standardized outcome measures. Conclusion Electromyographic biofeedback in pelvic rehabilitation seems to contribute to the faster achievement of continence in prostatectomized men compared to those who did not undergo any intervention. Additionally, helps to reduce pad weight.

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Abstract Cancer is a leading cause of death worldwide, and despite the introduction of new therapeutic approaches for advanced cases aimed at improving patient survival, only a subset of patients benefits from a complete response. In this context, there is a growing need for new cancer biomarkers and therapeutic strategies, and the use of Extracellular Vesicles (EVs) has been widely explored in various approaches. As circulating lipid-bilayer particles carrying a variety of biological information from tumor cells, EVs can be employed as good biomarkers of diagnosis, prognosis, therapy evaluation, and as adjuvants in cancer treatment. In this review, we provide a brief overview of the different types of EVs and their biogenesis and discuss how tumor-derived EV cargo can serve as a potential biomarker in clinical settings through liquid biopsy. We also highlight recent advances in EV nanoengineering and their potential as adjuvants in cancer treatment. Finally, we discuss the key unknowns, gaps, and bottlenecks that must be addressed to fully integrate EVs into precision oncology.

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ABSTRACT Introduction The existing literature presents conflicting findings regarding the relationship between Age At Menarche (AAM) and depression. Thus, to address this gap, this systematic review and meta-analysis aimed to evaluate current evidence to clarify the association between AAM and depression. Methods Medline (PubMed), Scopus, Embase, Web of Science, and Google Scholar were searched from 2000 until June 2024 to include cross-sectional, case-control, and cohort studies. The quality of the evidence was assessed using the Newcastle-Ottawa Scale (NOS) instrument. The odds ratio (OR) of depression and its 95 % Confidence Interval (95 % CI) were calculated using the random effects model and inverse variance method. The protocol is registered in PROSPERO, number CRD42024551838. Results From a total of 2175 search records, 13 studies were included comprising 434,838 participants with NOS scores ranging from 7 to 9. The present findings showed that early menarche is associated with significantly higher odds of depression compared to both normative AAM (OR = 1.36, 95 % CI: 1.20–1.53) and late AAM (OR = 1.52, 95 % CI 1.22–1.90). Also, females with later menarche had lower odds of depression compared to females with normal AAM (OR = 0.91, 95 % CI 0.76–1.09); however, this association was not statistically significant. Conclusion The present findings demonstrated that early menarche is associated with elevated odds of depression compared to females of both normative AAM and late AAM.

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Abstract Over the past four years, pivotal discoveries have deepened the understanding of the relationship between genetic factors and SARS-CoV-2 infection. Numerous genes associated with severe COVID-19 suggest a potential genetic predisposition, which may help explain why some individuals develop more serious illnesses. Emerging evidence highlights the role of genes involved in pulmonary immunity, such as Forkhead box Protein P4 (FOXP4), whose increased expression in lung tissue has been linked to more severe disease. Other genes - Transmembrane Protease Serine-2 (TMPRSS2), Leucine Zipper Transcription Factor Like-1 (LZTFL1), Solute Carrier family 6 member 20 (SLC6A20), Tyrosine Kinase-2 (TYK2), Angiotensin-Converting Enzyme (ACE), and FYVE and Coiled-Coil Domain-Containing-1 (FYCO1) - have also been implicated in COVID-19 severity. In contrast, certain genetic variants - such as the T-allele of rs12329760 in the TMPRSS2 gene and rs35705950-T in the Mucin-5B (MUC5B) gene - may confer protection against severe disease. Overall, the evidence suggests that genetic factors can influence both susceptibility to and protection from severe COVID-19, although these associations are likely shaped by complex interactions with environmental, behavioral, and other biological factors. This review summarizes current knowledge on genetic determinants linked to COVID-19 outcomes.

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Abstract This review synthesizes current evidence regarding optimal breast cancer screening strategies for women with dense breasts, a population at increased risk due to decreased mammographic sensitivity. A systematic literature review was performed in accordance with PRISMA criteria, covering MEDLINE, EMBASE, CINAHL Plus, Scopus, and Web of Science until May 2025. The analysis examines advanced imaging techniques such as digital breast tomosynthesis (DBT), contrast-enhanced spectral mammography (CESM), ultrasound, and magnetic resonance imaging (MRI), assessing their effectiveness in addressing the shortcomings of traditional mammography in dense breast tissue. The review rigorously evaluates the incorporation of risk stratification models, such as the BCSC, in customizing screening regimens, in conjunction with innovative technologies like liquid biopsy and artificial intelligence-based image analysis for improved risk prediction. A key emphasis is placed on the heterogeneity in international screening guidelines and the challenges in translating research findings to diverse clinical settings, particularly in resource-constrained environments. The discussion includes ethical implications regarding compulsory breast density notification and the possibility of intensifying disparities in health care. The review ultimately encourages the development of evidence-based, context-specific guidelines that facilitate equitable access to effective breast cancer screening for all women with dense breasts.

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Abstract Medical confidentiality is a fundamental element of the doctor-patient relationship, ensuring a secure environment for sharing sensitive information. This narrative review examines the ethical and legal challenges faced by physicians in Brazil when balancing professional secrecy with the legal duty to report, particularly in the context of criminal investigations. Grounded in the core bioethical principles of autonomy, beneficence, non-maleficence, and justice, the study analyzes Brazilian constitutional and infra-constitutional norms, including the Penal Code, the Code of Criminal Procedure, and the Code of Medical Ethics. The methodology is qualitative and descriptive-analytical, based on thematic and interpretive analysis of legal documents, court decisions, professional guidelines, and ethical frameworks. Comparative perspectives from Portugal, the United States, and international declarations (e.g., WMA Geneva Declaration, UNESCO Bioethics Declaration) are also included to situate Brazil’s legal approach in a global bioethical context. The study highlights the risks of breaching confidentiality without just cause, emphasizing real-life cases involving abortion, HIV disclosure, and unlawful access to patient data. Findings indicate that while breaches may be justified in exceptional situations ‒ such as imminent risk to third parties ‒ confidentiality must remain the standard. The article concludes that ethically informed and legally compliant medical practice requires a careful balance between respecting patient privacy and fulfilling public health and judicial responsibilities. Upholding confidentiality strengthens the therapeutic alliance, protects vulnerable individuals, and ensures alignment with both national law and international bioethical standards.

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Abstract Objective To provide an updated overview of Premature Ovarian Insufficiency (POI), focusing on the current evidence regarding diagnosis, hormonal treatment, and clinical management. Methods A narrative review was conducted using data from the FEBRASGO protocol and updated international guidelines, complemented by recent publications from PubMed and Scopus. Results POI affects up to 3.5 % of women under 40-years of age and is associated with significant physical and psychological repercussions due to early hypoestrogenism. The diagnosis is established based on persistent amenorrhea and elevated FSH levels, and etiological diagnosis should be encouraged. Hormone Therapy (HT) is the cornerstone of management and must be continued at least until the age of natural menopause. New evidence emphasizes the use of l17β-estradiol (preferably non-oral route) combined with cyclic or continuous progestogens. Fertility preservation and sexual health should be addressed early in management. Conclusion Hormonal replacement in POI is essential to prevent long-term complications and improve quality of life. Guidelines for healthy lifestyle habits should be reinforced and clinical decisions should be individualized, guided by age, symptom profile, and reproductive plans.

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Abstract Purpose Evaluate the effects of resistance and aerobic training on the quality of life (QoL), functional capacity, and body composition of patients with liver cirrhosis. Methods Studies published in the MEDLINE database via PubMed, Cochrane Library, and Web of Science were analyzed. Patients with liver cirrhosis who performed aerobic or resistance exercises in the experimental group and controlled and randomized clinical trials (RCTs) were included, whereas publications with only abstracts, control groups that performed aerobic and/or resistance training, and studies that included cointervention in the experimental and control procedures were excluded. Study variables were QoL, VO2peak, body mass index (BMI), distance covered in the 6-minute walk test (6 MWT), and thigh circumference. PRISMA systematization was used to prepare this review. Results Six RCTs were included in this review, including 244 participants aged 53-63 years with Child-Pugh stages A, B, or C, and mostly men. With QoL as a continuous variable, the difference in standardized means was 0.36 [0.01 - 0.76]; p = 0.04 for studies that performed resistance training. With 6 MWT as a continuous variable, significant improvement was seen after resistance and aerobic training, and the difference in means was 49.39 [16.53 - 82.24]; p = 0.03. No difference was observed after performing aerobic and resistance exercises in relation to VO2peak, thigh circumference, or BMI (p > 0.05). Certainty of evidence assessed by the GRADE was between very low and moderate. Conclusion Aerobic and resistance physical training appear to improve the QoL and functional capacity without changing body composition in patients with liver cirrhosis.

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Abstract Gastroesophageal reflux disease is a common digestive disorder, typically classified into three types based on its pathological characteristics: erosive esophagitis, non-erosive reflux disease, and Barrett's esophagus. Recently, a subset of patients has exhibited poor responses to standard treatments, and they have been diagnosed with refractory gastroesophageal reflux disease. The etiology of refractory gastroesophageal reflux disease is multifactorial, and its management remains challenging, making it a focus of current research. This review aims to systematically summarize the etiology of refractory gastroesophageal reflux disease and evaluate integrated treatment strategies combining traditional Chinese and Western medicine with the purpose of guiding clinical practice.

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Abstract Objective To evaluate the current evidence in the literature about partial prostatectomy as a treatment for localized prostate cancer. Methods A systematic search of nine databases was conducted up to December 2024 to identify studies involving patients with localized prostate cancer who underwent partial prostatectomy reporting clinical epidemiological characteristics, diagnostic strategies, histopathological findings, tumor staging, functional and oncological outcomes. The primary outcome was biochemical recurrence rate. Secondary outcomes were overall survival, disease-free survival, erectile dysfunction, urinary incontinence, and perioperative complications. The extracted data were systematically synthesized. Results The authors analyzed five studies with a total of 48 patients (three prospective and two retrospective), all with low- or intermediate-risk disease. The mean surgical duration ranged from 129.2 to 208 min, with a single Clavien-Dindo Grade III complication reported. Only one study defined and reported biochemical recurrence, with a rate of 28 %. Urinary continence was preserved in 92 %-100 % of cases, while erectile function in 40 %-100 % ‒ which may represent a point of concern for this procedure. Overall survival and disease-free survival were consistently reported at 100 %. The lack of standardized reporting and the absence of randomized clinical trials prevented the performance of a meta-analysis and hindered the applicability of the findings to clinical practice. Conclusion Randomized clinical trials are still needed to provide stronger evidence regarding partial prostatectomy, as current data remain insufficient to support its routine use. With further research, partial prostatectomy may become an option for patients with favorable and intermediate-risk disease with unilateral lesions and concordance between magnetic resonance imaging and biopsy findings. Until then, radical prostatectomy remains the cornerstone of treatment for this patient profile.

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Abstract Bronchial Asthma, characterized by chronic airway inflammation and remodeling, poses significant clinical challenges. Long-term use of conventional therapies often leads to metabolic complications and drug resistance. The bioactive alkaloid Tetramethylpyrazine, derived from Ligusticum chuanxiong Hort. (Apiaceae), demonstrates multi-target therapeutic potential through pathway modulation. TMP restores Th1/Th2 and Th17/Treg immune balance via Gαs/cAMP/PKA and AMPK/NF-κB signaling while suppressing ORMDL3-mediated collagen deposition. Clinical evidence demonstrates effective symptom alleviation with minimal adverse effects, establishing TMP as a promising complementary strategy for asthma management.

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Abstract Background Postoperative Nausea and Vomiting (PONV) is one of the patient-important outcomes, as its management reduces morbidity associated with surgery. This systematic review with meta-analysis aims to evaluate the efficacy and safety of prophylactic aprepitant and fosaprepitant within the first 24 hours after surgery in adult patients who underwent general anaesthesia. The authors The authors combined the outcomes only with identical evaluation times. Methods The authors The authors searched six databases (MEDLINE, EMBASE, CENTRAL, WHO, ICTRP, SCIELO) for randomized controlled trials that compared aprepitant or fosaprepitant for PONV against control in different time assessments within the first 24 hours after surgery in adult patients who underwent general anaesthesia. Results This systematic review includes 35 articles with 6241 participants in total. The authors The authors observed that aprepitant, from 0h to 24 h after surgery, significantly reduces the incidence of nausea (RR = 0.80, 95 % CI 0.67-0.97, I2 = 42 %, p = 0.07), vomiting (RR = 0.41, 95 % CI: 0.31-0.55, I2 = 51 %, p = 0.008), the use of rescue antiemetics (RR = 0.79, 95 % CI 0.66-0.95, I2 = 54 %, p = 0.009), and increases the complete response rate (RR = 1.19, 95 % CI 1.04-1.37, I2 = 51 %, p = 0.04). On the other hand, fosaprepitant, from 0 to 24 hours after surgery, showed a reduction only in the incidence of vomiting (RR = 0.35, 95 % CI 0.19-0.64, I2 = 33 %, p = 0.20). Conclusion Aprepitant reduces the incidence of postoperative nausea, vomiting and the use of rescue antiemetics and increases the complete response rate among adult patients from 0 to 24 hours after surgery. Fosaprepitant reduces the incidence of vomiting from 0 to 24 hours after surgery. Findings primarily reflect female patients; male applicability requires further study. PROSPERO registry CRD42023427076.

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Abstract Background Pulmonary Epithelioid Haemangioendothelioma (PEH) is a rare vascular tumor with specific clinical symptoms (e.g., cough, chest pain) and imaging manifestations (multiple nodules in both lungs) that can be easily misdiagnosed or lead to a poor prognosis. Objective To systematically analyse the pathological features, diagnostic challenges, and therapeutic strategies of PEH to provide evidence for its clinical management. Main findings Diagnostic basis: Histologically, spindle cells, cytoplasmic vacuolation and vasculogenic characteristics. Immunochemically, strong positivity for CD31, CD34, and ERG supports an endothelial origin. The genetic biomarker WWTR1-CAMTA1 is present in most patients. The treatment strategy for patients is as follows: surgery is the preferred option for localized lesions (5-year survival rate > 80 %); antiangiogenic agents or chemotherapy can be used for those with multiorgan involvement, but the efficacy is limited. Prognostic risk factors included multiorgan metastasis, male sex, and age ≥ 55 years. Future directions Precision treatment exploring targeted gene fusions (e.g., WWTR1-CAMTA1, YAP1-TFE3); research on the effects of Bartonella infection and EGFR overexpression on tumor progression; and the development of early diagnostic models based on radiomics.

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Abstract Pneumonia is one of the main causes of intensive care unit admission and death in Brazil. There is a need to standardize the use of microbiological tests for the diagnosis of pneumonia. Objective To evaluate microbiological diagnostic data for severe pneumonia. Method: Comparative studies that evaluated the microbiological diagnosis of community pneumonia and hospital-acquired pneumonia were analyzed. The literature review was guided by two questions and used flowcharts prepared by experts. Results and Discussion Diagnostic tests for pneumonia should be requested based on the severity of the disease, the patient´s immune status, and the risk of infection by multidrug-resistant bacteria. Gram staining may aid in excluding S. aureus pneumonia and evaluating the quality of respiratory samples, while culture of these clinical samples may identify the infectious agent in up to half of the cases and allow antimicrobial susceptibility testing to be carried out. Blood cultures have a low sensitivity but may be useful for diagnosing extrapulmonary infections or situations involving sepsis or septic shock. Rapid molecular panels have high sensitivity and specificity for viral and bacterial targets for both types of pneumonia, and their use can reduce the length of hospital and intensive care stays and allow optimization of antimicrobial therapy. RT-PCR is highly accurate in diagnosing SARS-CoV-2 pneumonia. Conclusion The rational use of molecular panels for the diagnosis of severe pneumonia can reduce the length of hospital and intensive care stays and 90-day mortality.

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Abstract Introduction After hospitalization for COVID-19, patients may present impairment in functionality and require physical therapy after hospital discharge for functional recovery. Objective To understand the association between Covid-19 functional impacts and physical therapy indication and access 30 days and 1 year after hospital discharge of severely and critically ill patients. Methods Cross-sectional study with two assessments: 30 days and one year after hospital discharge, in individuals ≥ 18 years of age, admitted to a referral hospital in São Paulo between June 2020 and July 2021. A convenience sample of 345 patients was used. The Poisson test was used to estimate the prevalence ratio for the association between Covid-19 functional impacts and physical therapy indication and access, with ≤ 0.05 considered significant. Results Of the 185 patients included, 67 % (n: 104) were indicated for physical therapy and the majority (53 %; n:79) could not access it 30 days after hospital discharge. Post-Covid-19 functional limitations were associated with physical therapy indication (PR: 1.69; 95 %CI 1.1-2.5) and impairment in basic activities of daily living (BADLs) with access 30 days (PR: 1.81; 95 %CI 1.2 -2.6) and 1 year after discharge (PR: 1.70; 95 %CI 1.2-2.3). Physical therapy indication was significant, with a 4.07 and 2.06 likelihood of access 30 days and 1 year after discharge. Conclusion Despite the lack of functional criteria at discharge, patients with poor functional performance perceived the need for physical therapy indication and referral. Indication was essential for access to physiotherapy within the healthcare network.

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Abstract This study aimed to perform a comprehensive examination of the prevalence of psoriasis in people with HIV, aiming to offer valuable evidence for informed resource allocation and policy formulation. Methods: The authors systematically gathered literature on psoriasis prevalence among those with HIV from multiple sources. These sources comprise databases such as CNKI, VIP, Wanfang Database, PubMed, Cochrane Library, and EMBASE up to June 30, 2024. Additionally, manual searches were conducted to supplement the data collection process. Two independent researchers carried out literature screening, relevant data extraction, and assessment of potential bias. Meta-analysis was conducted with RevMan 5.3 software. Results Fifteen investigations were incorporated, involving 130,032 individuals with HIV. The meta-analysis of these fifteen pieces showed that the occurrence rate of psoriasis in those infected with HIV was 2.0 % (95 % CI: 2.0 %-2.0 %). Divide the survey years into two subgroups: 2000-2022 years and 1984-1994 years, with prevalence rates of 1.00 % (1.00 %-1.00 %) and 5.00 % (3.00 %-7.00 %), respectively. According to regional latitude, it is divided into two subgroups: latitude ≥ 30° N/S and latitude ˂ 30° N/S, with prevalence rates of 2.0 % (1.0 %-2.0 %) and 3.0 % (2.0 %-5.0 %), respectively. The results of the funnel plot, Begg's test (Z = 0.038, p = 0.856), and Egger's test (t = 4.68, p ˂ 0.001) showed publication bias in the literature. Sensitivity analysis revealed no substantial difference between the analysis of the FEM and that of the REM for psoriasis prevalence, suggesting that the stability of the findings in this study is satisfactory. Conclusion The incidence of psoriasis in HIV-infected individuals has shown a slight downward trend, and the differences are not significant in different latitude regions.

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Abstract Background Anti-neutrophil cytoplasmic Antibody-Associated Vasculitis (AAV) is an immune-mediated disease characterized by Anti-Neutrophil Cytoplasmic Antibody (ANCA) positivity. Patients with AAV are known to be at high risk for the occurrence of Interstitial Lung Disease (ILD). The authors aimed to explore the risk factors in patients with AAV-ILD to enhance awareness among the public and healthcare providers, and to facilitate the timely adoption of effective strategies for prevention and management. Methods The authors searched PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure Database (CNKI), the WanFang Database, Chinese biomedical literature service system (SinoMed), and China Science and Technology Journal Database (VIP) for studies that focused on the risk factors in patients with AAV-ILD from database inception to 21 September 2024. Methodological quality was assessed using the Newcastle-Ottawa Scale (NOS). The authors used a random-effects model or a fixed-effects model to evaluate the underlying risk factors of AAV-ILD. Results A total of 25 studies were included, including 13 case-control studies, 5 cohort studies, and 7 cross-sectional studies, respectively. The authors identified preliminary risk factors for AAV-ILD, including age, male, smoking history, KL-6, ESR, MPO-ANCA, cough, dyspnea, and HRCT findings such as honeycombing, interlobular septal thickening, and lattice shadows, Ear, nose & throat involvement, Hb, alb, BVAS, and fever. The study design type, follow-up (time), Country, sample, type of AAV, quality score, and were initially considered not to be sources of heterogeneity. Conclusions This study has preliminarily identified multiple risk factors associated with ILD in AAV patients, encompassing sociodemographic, lifestyle, and clinical factors. While these findings may serve as a reference for further investigation, large-scale prospective cohort studies or longitudinal research remain necessary for validation. Systematic review registration PROSPERO, identifier CRD42024592874.

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Abstract This study highlights the use of REDCap as an effective tool for the clinical follow-up of bariatric surgery patients. By manually entering data from medical records spanning 2000 to 2020, the study provides insights into REDCap’s capabilities in organizing and analyzing large datasets. Key findings demonstrate its value in monitoring weight changes, biochemical parameters, and adherence to supplementation protocols, contributing to improved patient management and research efficiency. While REDCap’s utility is clear, limitations include the retrospective and single-site nature of the study, which may affect generalizability. Future efforts will focus on expanding data collection and integrating the database into routine clinical workflows.

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Abstract Introduction High-Intensity Interval Training (HIIT), involving brief bouts of intense exercise with rest or low-intensity intervals, benefits cardiovascular, metabolic health, and body composition. However, its impact on serum metal concentrations in adults remains unclear. This study investigated the effects of a 16-week HIIT protocol on serum metal levels. Methods Adults over 18-years-old with a Body Mass Index (BMI) above 25 kg/m2. Participants trained for 40-minutes three times per week, with two supervised and one unsupervised session. Each session included a 10-minute warm-up at 70 % of maximum Heart Rate (HRmax), followed by four 4-minute intervals at 90 % HRmax, interspersed with three 3-minute active pauses at 70 % HRmax. Before and after the 16-week intervention, anthropometric and biochemical parameters were assessed. Results Fifteen participants [mean (SD) age: 42 (6); BMI: 30.6 (2.7)] completed the study. Significant reductions were observed in both toxic (e.g., mercury, lithium, lead, nickel, aluminum) and essential metals (e.g., manganese): mercury (p = 0.025, Cohen’s d = 0.58), lithium (p = 0.009, d = 1.01), aluminum (p = 0.025, d = 0.49), manganese (p = 0.009, d = 0.96), nickel (p = 0.025, d = 0.58), and lead (p = 0.025, d = 0.40). A negative correlation was found between the change in hip circumference and manganese (r = -0.538; p = 0.047), and a positive correlation with nickel (r = 0.600; p = 0.023). Conclusion These findings suggest potential associations between changes in metal concentrations and anthropometric outcomes following HIIT.

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Abstract Background This study aimed to compare the chronic effects of High-Intensity Interval Training (HIIT) aqua aerobics performed once a week (G1) versus twice a week (G2) on sleep quality, daytime sleepiness, anxiety, and depression in older adults with multimorbidities. Methods Both groups performed the same exercises (9 in total) with identical volume (4 sets of 30 seconds of activity followed by 30 seconds of rest) and intensity (80 %-90 % of Heart Rate max, corresponding to 8-9 on the Borg Scale), in 40-minute sessions. Mental health parameters were assessed 48 hours after the last training session. To analyze the effects of HIIT, a two-way analysis of variance (anova), with Bonferroni post hoc tests, was used with a significance level set at p < 0.05. Results Initially, one hundred and twenty-nine older adults were assessed for eligibility. Fifty-six older adults with multimorbidities, including diabetes, hypertension, and depression, completed the study. Significant improvements were observed only in G2 (sessions performed twice a week), with increases in sleep quality (+49 %, p = 0.032) and reductions in daytime sleepiness (-50 %, p = 0.041), anxiety (-45 %, p = 0.047), and depression (-62 %, p = 0.017). Conclusions The results suggest that HIIT aqua aerobics improves mental health outcomes in older adults with multimorbidities only when performed at least twice a week. Trial registration Brazilian Registry of Clinical Trials (ReBEC) RBR-9kqwd5f. Registered on January 14, 2024.

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Abstract Objective This is a methodological study. The goal is to describe and implement statistical tests based on the Youden index to evaluate the performance of diagnostic tests, using Prostate-Specific Antigen (PSA) as the primary example and including additional diagnoses to illustrate how these evaluations can be generalized. Methods Quantitative analysis using the Youden index was applied to assess diagnostic test performance across three different experimental designs: a single condition, two independent conditions (between-groups), and two dependent conditions (within-group), revisiting 2 × 2 tables from previous studies. Results The Youden method combines sensitivity and specificity into a single index and requires only a 2 × 2 contingency table summary, incorporating both point estimates and confidence intervals. This allows for the evaluation of many studies where raw data are unavailable. Conclusion PSA seems insufficient for effective prostate cancer screening, despite numerous efforts over decades claiming improvements in sensitivity, specificity, or diagnostic capability. However, the statistical method presented here can be applied to any symptom, sign, or laboratory test, current or future. By providing open-source code, the authors aim to bridge the gap between statistical methods and their practical application, improving diagnostic processes. The R package and other supplemental materials to replicate this study are available on Harvard Dataverse at https://doi.org/10.7910/DVN/5QTMBW.

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Abstract Background To explore whether β-glucan combined with anti-PD-L1 reverses the immunosuppressive Tumor Microenvironment (TME) in residual pancreatic cancer after Microwave Ablation (MWA). Methods The effect of β-glucan on the activation of Dendritic Cells (DCs) was assessed in vitro. Subcutaneous and orthotopic pancreatic tumor models with incomplete MWA were treated with β-glucan, anti-PD-L1, or both. Tumor growth, immune cell populations in TME, and survival were analyzed. Results β-glucan elevated MHCII+DCs, meanwhile combination therapy increased the CD8+/Treg ratio, suggesting enhanced anti-tumor immunity. This immunomodulatory effect translated into the combination therapy demonstrated significantly greater efficacy in suppressing residual tumor growth and prolonging overall survival. Conclusion β-glucan administration increased MHCII+DCs, and in combination therapy, this led to an elevated CD8+/Treg ratio, enhancing the anti-tumor immunity. β-glucan therapy reversed the immunosuppressive TME in pancreatic cancer following MWA ablation, thereby enhancing the anti-PD-L1-associated antitumor responses. This resulted in a significant suppression of residual tumor growth, leading to prolonged survival in mice establishing orthotopic pancreatic tumors.

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ABSTRACT Objective: Periodontitis is a multifactorial progressive disease predominantly related to bacterial infection. Human Periodontal Ligament Stem Cells (hPDLSCs) are important cell populations for repair and regeneration in periodontal tissue. Recently, Methyltransferase-Like-3 (METTL3) is demonstrated to be closely related to the osteogenic differentiation of stem cells by modulating m6A levels. Additionally, through the bioinformatic analysis, CARD11 was demonstrated to be closely related to periodontitis. Therefore, this study was performed to investigate the role of METTL3 in the osteogenic differentiation of hPDLSCs and the periodontitis rat model. Methods The biomarkers of hPDLSCs were analyzed by flow cytometry. qRT–PCR was performed to measure METTL3 and CARD11 levels. The protein levels of Runx2, Osterix, Osteocalcin, p-p65, and p-IκBα were detected by western blotting. Alizarin red and alkaline phosphatase staining were carried out. The relationship between METTL3 and CRAD11 was confirmed by RIP and dual luciferase report. Results: The results showed that METTL3 and CARD11 were dramatically upregulated in periodontitis patients. In addition, METTL3 silencing dramatically decreased the m6A and mRNA levels of CARD11 and increased the Runx2, Osterix, and Osteocalcin levels. Alizarin red and alkaline phosphatase staining showed that METTL3 silencing promoted the osteogenic differentiation of hPDLSCs. Additionally, overexpression of CARD11 neutralized the role of CARD11 in hPDLSCs and inactivated the NF-κB signaling pathway. Finally, METTL3 knockdown relieved the periodontitis progression in vivo. Conclusions In conclusion, METTL3 participates in periodontitis progression by regulating CARD11 levels through the NF-κB signaling pathway.

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ABSTRACT Objective: To analyse factors associated with fatal occupational accidents in Brazil in 2023, using data from the Notifiable Diseases Information System (SINAN). Methods: A quantitative, analytical, retrospective case-control study was conducted with 267,482 occupational accident notifications, of which 2716 (1 %) were fatal. Univariate and multiple logistic regression analyses were performed, with significance set at p < 0.05. Results: Most injured workers were male (77.2 %), non-white (51.9 %), and had at least completed high school (43.9 %). The average age was 36.5-years. About 75.8 % were formally employed, and 41 % had less than one year of job experience. Accidents mainly occurred in the morning (50.5 %) and on the employer’s premises (66.6 %). Logistic regression showed that male workers had a higher risk of fatality (OR=2.59; 95 % CI 2.07–3.24). The risk increased progressively with age, being 3.89-times higher among workers aged 60–65 years than those aged 16–19. Education had a protective effect compared to illiteracy. Workers in the North, Northeast, and Central-West had a 25 % higher risk of death than those in the South and Southeast. Informal work increased fatality odds by 1.77 times, and workers with over 20 years of experience had a 43 % higher risk than those with under one year. Night-time accidents were 1.65 times more lethal than daytime incidents. Race, accident location, type, and body part affected were not significant in multivariate analysis. Conclusion: Vulnerable groups ‒ men, older workers, the illiterate, informal workers, and those in underdeveloped regions ‒ face higher fatality risks, highlighting the need for targeted policies such as mandatory safety training for informal workers and regional surveillance strategies.

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ABSTRACT Background and aim: Portal Vein Thrombosis (PVT) is the most common cause of Portal Hypertension (pH) in children. This study aimed to present the experience of a large university center by analyzing patients with portal hypertension caused by portal vein thrombosis in search of prognostic factors, types of treatments, and results. Methods: We retrospectively analyzed 110 pediatric patients treated from 2000 to 2019, who were divided into two groups: endoscopic procedures (67 patients) and surgical assistance protocols (43 patients). Results: Among the patients who underwent the surgical protocol, 22 underwent Meso-Rex Shunt (MRS) and 21 underwent other surgical techniques: distal splenorenal shunt (DSRS - 11 patients), azigoportal dissociation with partial splenectomy (6 patients), and mesocaval shunt (4 patients). Five patients with meso‑Rex developed graft thrombosis (5/22, 22.72 %). There were no differences between the groups regarding endoscopic findings (first and last), no correlation with the need for surgery, and no definition of the initial endoscopic characteristics that could predict worsening disease. The only observed difference was the increase in platelet count in the surgical group (median 25.02 thousand/mL, interquartile interval 118.00), which was greater than that observed in the endoscopic group (-42.50 thousand/mL, interquartile interval 56, p < 0.001, Mann-Whitney test). Only umbilical catheterization could predict the need for exclusive endoscopic treatment. Conclusions: As the evolution of children treated endoscopically was not different from that of children treated surgically, we conclude that a more conservative approach should be adopted, whenever possible.

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ABSTRACT Introduction and objectives: After Liver Transplantation (LT), patients often gain weight and develop metabolic comorbidities. This study aimed to assess the prevalence and severity of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) after LT and the incidence of New-Onset Diabetes After LT (NODALT). Methods: Post-LT patients were recruited from an outpatient clinic. Hepatic ultrasound and 2D shear-wave elastography were performed. Results: A total of 142 patients were included, 63 % male with median age 60 (Interquartile Range [IQR] 47‒68 years). Median follow-up time post-LT was 137 (IQR 77‒205 months). MASLD was diagnosed in 26 %. Patients with MASLD exhibited a higher prevalence of central obesity (92 % vs. 68 %, p = 0.006), diabetes (65 % vs. 38 %, p = 0.005), hypertriglyceridemia (51 % vs. 26 %, p = 0.008), and metabolic syndrome (69 % vs. 41 %, p = 0.006) compared to those without MASLD. MASLD was independently associated with hypertriglyceridemia (Odds Ratio [OR = 2.80], 95 % Confidence Interval [95 % CI 1.22‒6.43], p = 0.015) and post-LT diabetes (OR = 2.65, 95 % CI 1.15‒6.10, p = 0.022). NODALT occurred in 36 % and was independently associated with older age (OR = 1.05, 95 % CI 1.01‒1.08, p = 0.01), time from LT (OR = 1.01, 95 % CI 1.003‒1.016, p = 0.006), body mass index (OR = 1.12, 95 % CI 1.02‒1.22, p = 0.02) and MASLD (OR = 2.99, 95 % CI 1.13‒7.92, p = 0.028). Advanced fibrosis occurred in 9 % of MASLD patients, which was similar from patients without MASLD. Conclusion: After LT, the prevalence of MASLD was 26 % ant the incidence of NODALT was 36 %. MASLD was associated with diabetes and hypertriglyceridemia, while NODALT was linked to older age, longer follow-up post-LT and MASLD. These findings emphasize the importance of preventing post-LT metabolic complications.

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ABSTRACT Background: Human Periodontal Ligament Stem Cells (PDLSCs) represent a subset of mesenchymal stem cells originating from the periodontal ligament, a connective tissue responsible for anchoring teeth to alveolar bone. This study explored the functional role of Methyltransferase-Like-1 (METTL1)-mediated N7-methylguanosine (m7G) modification in regulating the osteogenic differentiation capacity of PDLSCs. Methods: PDLSCs were isolated from periodontal ligament tissues. Osteogenic differentiation was assessed through Alkaline Phosphatase (ALP) activity assays and Alizarin Red S (ARS) staining. Expression levels of Runt-related Transcription Factor-2 (RUNX2), Osteocalcin (OCN), and Osteopontin (OPN) were quantified using Real-Time quantitative Polymerase Chain Reaction (RT-qPCR). Western blot analysis was employed to detect protein expression of METTL1, NOP2/Sun RNA Methyltransferase-2 (NSUN2), and WD Repeat Domain-4 (WDR4). Total m7G content in PDLSCs was measured via m7G dot blot assays. The interaction between METTL1 and RUNX2 was validated using luciferase reporter assays. Results: The present findings demonstrated that METTL1 exhibited elevated expression levels in PDLSCs, with further upregulation during osteogenic induction. METTL1 knockdown significantly impaired osteogenic differentiation, characterized by decreased ALP activity, reduced ARS staining intensity, and downregulated osteogenic marker gene expression. Mechanistically, the authors identified that METTL1 enhanced m7G modification of key osteogenic genes, including RUNX2, OCN, and OPN, thereby improving their mRNA stability and translational efficiency. Notably, forced overexpression of RUNX2 partially reversed the osteogenic differentiation defects induced by METTL1 suppression. Conclusion: METTL1 promotes osteogenic differentiation in PDLSCs through m7G modification-mediated stabilization of RUNX2 expression. This discovery unveils a novel epigenetic regulatory mechanism involving m7G modification in periodontal tissue regeneration, offering potential therapeutic targets for bone defect repair applications.

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ABSTRACT Objective: This investigation evaluates the efficacy of acupuncture used alongside conventional interventions for Perimenopausal Insomnia (PMI). The research aims to provide clinically relevant evidence, support individualized treatment planning, and improve sleep quality and overall well-being in perimenopausal women. Methods: A systematic search was conducted up to December 2024, encompassing six major databases, including international (PubMed, Web of Science, Cochrane Library, Embase) and Chinese-language sources (CNKI, Wanfang). The search focused exclusively on Randomized Controlled Trials (RCTs) investigating acupuncture as an adjunctive treatment for PMI. To evaluate result stability and identify potential heterogeneity sources, the authors performed sensitivity and subgroup analyses utilizing Review Manager (v5.4) and Stata (v15.0). Results: The study included 32 RCTs involving 2,673 participants. Compared with control interventions, the use of adjunctive acupuncture was associated with significantly improved therapeutic effects (RR = 1.25, 95 % CI [1.20, 1.30]). The observation group receiving adjunctive acupuncture therapy demonstrated significant advantages over the non-acupuncture group in improving: Pittsburgh Sleep Quality Index (PSQI) (SMD = -1.00, 95 % CI [-1.21, -0.79]), Menopause-Specific Quality of Life (MENQOL) (SMD = -0.56, 95 % CI [-0.88, -0.23]), Traditional Chinese Medicine Syndrome Score Scale (TCMSSS) (SMD = -1.40, 95 % CI [-2.55, -0.24]), Adverse Drug Reactions (ADR) (RR = 0.35, 95 % CI [0.17, 0.71]), Epworth Sleepiness Scale (ESS) (SMD = -0.57, 95 % CI [-0.83, -0.31]), and Insomnia Severity Index (ISI) (SMD = -0.94, 95 % CI [-1.43, -0.46]). Conclusion: Acupuncture as an adjunctive therapy enhances treatment outcomes for PMI, offering superior efficacy with minimal risks. Given the intrinsic limitations of the present study, additional investigations are necessary to substantiate these outcomes. Systematic Review Registration: PROSPERO database (ID: CRD420251020144).

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Abstract Purpose Sorafenib-induced Hand-Foot Skin Reaction (HFSR) significantly impairs patient quality of life, yet its underlying mechanisms remain poorly understood. This study investigates the pivotal role of Epiregulin (EREG), an Epidermal Growth Factor Receptor (EGFR) ligand, in driving keratinocyte hyperproliferation and the pathogenesis of HFSR. Methods The authors established a murine HFSR model using oral sorafenib (100 mg/kg) and analyzed paw tissues for histopathological changes (H&E staining) and EREG expression (immunohistochemistry). In vitro, HaCaT keratinocytes were treated with sorafenib and recombinant EREG to assess proliferation (CCK-8 assay). Results Sorafenib-treated mice exhibited hallmark HFSR features, including erythema, neutrophil infiltration, and thickened keratin layers (p < 0.001). EREG expression was markedly upregulated in affected tissues (p < 0.001). Notably, recombinant EREG dose-dependently enhanced HaCaT cell proliferation (p < 0.05), while sorafenib alone showed no direct proliferative effect. Conclusion The present findings identify EREG as a critical mediator of keratinocyte hyperproliferation in sorafenib-induced HFSR, offering a novel therapeutic target. Moreover, EREG expression may serve as a predictive biomarker for HFSR severity, guiding personalized prophylaxis. Clinical exploration of EREG inhibition could provide a tailored approach to alleviate HFSR, improving patient adherence and treatment outcomes.

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Abstract Background Chronic Kidney Disease (CKD) is a worldwide health problem. Researchers have reported the close relation of the Hemoglobin Glycation Index (HGI) with metabolism, inflammation, and prognosis of disease. The prognostic value of HGI in CKD patients has not been assessed. This study aims to explore the association between HGI and mortality in critically ill patients with CKD. Methods Data on critically ill patients diagnosed with CKD were extracted from the Medical Information Mart for Intensive Care-IV database. The HGI is the difference between an observed glycated hemoglobin A1c(HbA1c) and a predicted HbA1c obtained by inserting Fasting Plasma Glucose (FPG) into a regression equation describing the linear relationship between FPG and HbA1c in a reference population. The follow-up started on the patients’ first admission to the Intensive Care Unit (ICU). The primary outcome was 30-day mortality. 90-day and 365-day mortality were the secondary outcomes. Cox proportional hazards models were used to investigate the associations between HGI and mortality of CKD patients. Subgroup analyses were performed to assess the consistency of the association. Results 1,831 critically ill patients with CKD were included in the present study (64.1 % male, 60.2 % white, 71.93±12.72 years). For 30-day mortality, the Hazard Ratio (HR) value of the high-HGI group was 0.50 and 95 % Confidence Interval (95 % CI) was (0.39, 0.65) compared with the reference of the low-HGI group (p < 0.0001). When adjusted for age, gender and ethnicity, the adjusted HR (95 % CI) value of the high-HGI group was 0.53 (0.41, 0.68). When further adjusted for heart rate, diabetes mellitus, and SOFA score in Model II, the adjusted HR value of the high-HGI group was still statistically significant (HR = 0.57, 95 % CI: 0.44‒0.75, p < 0.0001). Similar results were also shown in the secondary outcomes of 90-day and 365-day mortality. Further subgroup analysis showed the above stable association between HGI and 30-day mortality of CKD patients. Conclusions High level of HGI is associated with reduced short- and long-term all-cause mortality of critically ill patients with CKD. HGI can independently predict the prognosis of critically ill patients with CKD.

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Abstract Objective This study aims to investigate the correlation between Systemic Immune-Inflammation (SII) index and Health Assessment Questionnaire (HAQ) scores and disease activity in patients with Rheumatoid Arthritis (RA). Methods Clinical and laboratory data of 132 RA patients, including SII index, disease activity scores, and HAQ scores were collected. The patients were categorized as moderate disease activity and High Disease Activity (HAD). Univariate and multivariate linear analyses were performed to find correlations between the SII index and HAQ with DAS28-CRP and DAS-ESR. Results The HAD-RA cohort had a higher SII index (1.28 [IQR: 0.97, 2.10] vs. 0.89 [IQR: 0.66, 1.27], p < 0.001) and HAQ (1.80 [1.40, 2.10] vs. 1.05 [IQR: 0.71, 1.40], p < 0.001). A relationship was found between the SII index, HAQ scores, and disease activity, where individuals with worse functional status had higher disease activity. Multifactor linear analysis further validated the independent correlation between the SII index and HAQ scores with RA disease activity. Decreased hemoglobin was a relevant factor affecting DAS28-CRP and DAS-ESR. The AUC of the SII index was 73.69 with a cutoff value of 0.93, and the AUC of HAQ was 84.41 with a cutoff value of 1.45. The combination of the two resulted in an AUC of 85.76, which increased the sensitivity and specificity to 83.99 % and 94.00 %, respectively. Conclusion Both the SII index and the HAQ scores are significantly associated with disease activity in RA patients. These insights support the accurate assessment of the disease, the design of personalized treatment plans, and the evaluation of treatment efficacy.

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Highlights VSIG4 is highly expressed in renal fibrosis tissues. VSIG4 may be an important mediator involved in renal fibrosis. VSIG4 may be a potential biomarker for renal fibrosis.

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Abstract Purpose This study aimed to explore the impact of treatment modalities on the survival outcomes of HER2-positive patients with early-stage invasive ductal breast cancer. Methods Hierarchical clustering analysis was used to identify distinct subgroups based on treatment modalities. Comparative analysis between the clusters identified significant treatment-related variables. Cox regression analysis was performed to construct a survival prediction model and nomogram incorporating these variables. Random Survival Forest (RSF) and SHapley Additive exPlanations (SHAP) analysis were employed for further validation and interpretation. Results A total of 9569 patients with early-stage HER2+ invasive ductal breast cancer were included, and five treatment-related clusters were identified using hierarchical clustering. Post-clustering analysis revealed that survival outcomes were influenced by various treatment factors, including time length from diagnosis to treatment, surgery approach, response to neoadjuvant therapy, combination with radiation, chemotherapy and/or systemic therapy, and treatment sequence. A prediction model and nomogram were developed, demonstrating good discriminatory ability and excellent predictive performance at 3-, 5-, and 8-years. Conclusions The study highlighted the importance of an aggressive and comprehensive treatment approach for patients with early-stage HER2-positive breast cancer. It emphasized the multifaceted nature of treatment outcomes and the need to consider multiple treatment factors beyond surgery alone. The developed survival prediction model provided valuable insights into the contribution of different treatment modalities to survival outcomes.

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Abstract Background The relationship between negative emotions and chronic respiratory diseases remains largely unexplored. In this study, we employ Mendelian Randomization (MR) to investigate the potential causal relationship between negative emotions and chronic respiratory diseases. Methods The data used in this study were derived from the publicly available GWAS summary statistics in the IEU Open GWAS database, including 12 negative emotions and 6 chronic respiratory diseases: asthma, Chronic Obstructive Pulmonary Disease (COPD), bronchiectasis, sarcoidosis, sleep apnea syndrome, and Idiopathic Pulmonary Fibrosis (IPF). Five models were established for MR analysis. Leave-one-out sensitivity analysis, MR pleiotropy residual sum, and MR-PRESSO, and Cochran's Q test were utilized to confirm heterogeneity and pleiotropy. Results This study indicates a causal relationship between negative emotions and chronic respiratory disease. Specifically, neuroticism, experiencing mood swings, feeling nervous and feeling worried were associated with an increased risk of asthma. Additionally, neuroticism, feeling miserable, experiencing mood swings, feeling guilty, and worrying too long after an embarrassing experience were associated with an increased risk of COPD. Similarly, neuroticism, experiencing mood swings, and feeling hurt increased the risk of sleep apnea syndrome. No causal association was observed between negative emotions and bronchiectasis, IPF, or sarcoidosis. In MVMR analysis, negative emotions were also associated with asthma and sleep apnea syndrome, while only the causal effect of experiencing mood swings persisted with COPD. Conclusion This study indicated a causal effect between negative emotions and chronic respiratory diseases, highlighting the importance of early intervention measures targeting negative emotions in the prevention of chronic respiratory diseases.