Miracle-dz/UniFAR-FTUs huggingface dataset:
Prospective analyses of testosterone and sex hormone‐binding globulin with the risk of 19 types of cancer in men and postmenopausal women in UK Biobank

We investigated the associations of estimated free and total circulating testosterone and sex hormone‐binding globulin (SHBG) with cancer risk in men and postmenopausal women, using a pan‐cancer approach, including 19 cancers in UK Biobank. Risk was estimated using multivariable‐adjusted Cox regression in up to 182 608 men and 122 112 postmenopausal women who were cancer‐free at baseline. Participants diagnosed with cancer within 2 years of baseline were excluded. Hazard ratios (HRs) and confidence intervals (CIs) were corrected for regression dilution bias using repeat measurements. We accounted for multiple testing using the false discovery rate. In men, higher free testosterone was associated with higher risks of melanoma and prostate cancer (HR per 50 pmol/L increase = 1.35, 95% CI 1.14‐1.61 and 1.10, 1.04‐1.18, respectively). Higher total testosterone was associated with an elevated risk of liver cancer (HR per 5 nmol/L = 2.45, 1.56‐3.84), and higher SHBG was associated with a higher risk of liver cancer (HR per 10 nmol/L = 1.56, 1.31‐1.87) and a lower risk of prostate cancer (0.93, 0.91‐0.96); the associations with liver cancer were partially attenuated after excluding men diagnosed within 4.7 years from baseline. In postmenopausal women, free and total testosterone and SHBG were associated with risks of endometrial (HR per 10 pmol/L = 1.59, 1.32‐1.90; HR per 0.5 nmol/L = 1.34, 1.18‐1.52 and HR per 25 nmol/L = 0.78, 0.67‐0.91, respectively) and breast cancer (1.32, 1.22‐1.43; 1.24, 1.17‐1.31 and 0.88, 0.83‐0.94, respectively). We report a novel association of free testosterone with malignant melanoma in men, and confirm known associations between testosterone and risks for prostate, breast and endometrial cancers. The association with liver cancer in men may be attributable to reverse causation.
Gastric Angiolipoma Resected with Endoscopic Submucosal Dissection

Angiolipoma is a benign fatty neoplasm that has components of proliferating blood vessels. These types of lesions commonly occur in the subcutaneous tissue of the limbs and trunk. Angiolipoma in the gastrointestinal tract is extremely rare, and the final diagnosis generally depends on histological examination of the excised biopsy. In most previously reported cases, the lesions were diagnosed and treated with surgical management. In this study, we report a case of gastric angiolipoma of approximately 4 cm in size that was diagnosed and treated with endoscopic submucosal dissection.
Revisiting the Functional Severity Scale of the Boston Carpal Tunnel Questionnaire, a comment concerning the use of digital communication technology

trodiagnostic examination in patients with radiculopathies. Muscle Nerve. 1998;21:1612-1631. 4. Merot O. Does the location of the disc herniation (medial or lateral) influence the clinical features and prognosis of lumboradiculalgia? [La localisation de la hernie discale (médiane ou latérale) influence-t-elle la présentation clinique et le pronostic de la lomboradiculalgie? ], Thèse de Médecine: Angers 2013. 5. Trummer M, Flaschka G, Unger F, Eustacchio S. Lumbar disc herniation mimicking meralgia paresthetica: case report. Surg Neurol. 2000;54: 80-81. 6. Cedoz ME, Larbre JP, Lequin C, Fischer G, Llorca G. Upper lumbar disk herniations. Rev Rhum Engl Ed. 1996;63:421-426. 7. Yang SN, Kim DH. L1 radiculopathy mimicking meralgia paresthetica: a case report. Muscle Nerve. 2010;41:566-568.
PI3K/AKT/MTOR and ERK1/2-MAPK signaling pathways are involved in autophagy stimulation induced by caloric restriction or caloric restriction mimetics in cortical neurons

Caloric restriction has been shown to robustly ameliorate age-related diseases and to prolong lifespan in several model organisms, and these beneficial effects are dependent on the stimulation of autophagy. Autophagy dysfunction contributes to the accumulation of altered macromolecules, and is a key mechanism of promoting aging and age-related disorders, as neurodegenerative ones. We have previously shown that caloric restriction (CR), and CR mimetics Neuropeptide Y (NPY) and ghrelin, stimulate autophagy in rat cortical neurons, however by unknown molecular mechanisms. Overall, we show that CR, NPY, and ghrelin stimulate autophagy through PI3K/AKT/MTOR inhibition and ERK1/2-MAPK activation. The knowledge of these kinases in autophagy regulation and the contribution to the understanding of molecular mechanism facilitates the discovery of more targeted therapeutic strategies to stimulate autophagy, which is relevant in the context of age-related disorders.
Phase transition in Poly(N-isopropylacrylamide) hydrogels induced by phenols

Poly(N-isopropylacrylamide) gels swollen at 20 °C in aqueous solutions of weak aromatic acids (phenol and resorcinol) display a volume transition at aromatic acid concentrations close to 50 mM. Owing to selective solvation, phenol exhibits an excess equilibrium concentration inside the swollen gels that is 7% greater than that in the surrounding bath, while for resorcinol the excess is 20%. The elastic modulus G of the gels at small strains follows the expected behavior of standard network theory, i.e., G ∝ φ1/3, where φ is the polymer volume fraction. Dynamic light scattering measurements, in which light from the thermodynamic fluctuations is heterodyned by that from the large-scale network heterogeneities, show that the collective diffusion coefficient Dc decreases at high aromatic content, while the Rayleigh ratio of the dynamic component of the scattering intensity, Rdyn, increases. No divergence of Rdyn close to the transition is observed, however, in accord with first-order nature of the transition.
Case-Control Study of Individuals with Discrepant Nucleocapsid and Spike Protein SARS-CoV-2 IgG Results

Abstract Background Laboratory-based methods for SARS-CoV-2 antibody detection vary widely in performance. However, there are limited prospectively-collected data on assay performance, and minimal clinical information to guide interpretation of discrepant results. Methods Over a 2-week period, 1080 consecutive plasma samples submitted for clinical SARS-CoV-2 IgG testing were tested in parallel for anti-nucleocapsid IgG (anti-N, Abbott) and anti-spike IgG (anti-S1, EUROIMMUN). Chart review was conducted for samples testing positive or borderline on either assay, and for an age/sex-matched cohort of samples negative by both assays. CDC surveillance case definitions were used to determine clinical sensitivity/specificity and conduct receiver operating characteristics curve analysis. Results There were 52 samples positive by both methods, 2 positive for anti-N only, 34 positive for anti-S1 only, and 27 borderline for anti-S1. Of the 34 individuals positive for anti-S1 alone, 8 (24%) had confirmed COVID-19. No anti-S1 borderline cases were positive for anti-N or had confirmed/probable COVID-19. The anti-N assay was less sensitive (84.2% [95% CI 72.1-92.5%] vs 94.7% [95% CI 85.4-98.9%]) but more specific (99.2% [95% CI 95.5-100%] vs 86.9% [95% CI 79.6-92.3%]) than anti-S1. Abbott anti-N sensitivity could be improved to 96.5% with minimal effect on specificity if the index threshold was lowered from 1.4 to 0.6. Conclusion Real-world concordance between different serologic assays may be lower than previously described in retrospective studies. These findings have implications for the interpretation of SARS-CoV-2 IgG results, especially with the advent of spike antigen-targeted vaccination, as a subset of patients with true infection are anti-N negative and anti-S1 positive.
Rationale and Design for a Higher (Dairy) Protein Weight Loss Intervention That Promotes Muscle Quality and Bone Health in Older Adults with Obesity: A Randomized, Controlled Pilot Study

Abstract In contrast to recommendations for young and middle-aged adults, intentional weight loss among older adults remains controversial and is inconsistently advised. Recent research suggests that a higher protein diet can mitigate loss of lean mass during periods of intentional weight loss among older adults with obesity; however, the effects of intentional weight loss on skeletal muscle and bone are not fully understood. The Dairy in the Diet Yields New Approaches for Muscle Optimization (DDYNAMO) trial is a 6-month, randomized, controlled pilot study assessing the effects of combining regular, generous intakes of high quality protein (30 g/meal; primarily from dairy) with caloric restriction (−500kcal/d) and low-intensity resistance exercise (30 min/3 times per week) on muscle quality, muscle composition, bone mineral density in men and women aged ≥60 years with obesity and mild to moderate functional impairment (Short Physical Performance Battery [SPPB] score ≥4 to ≤10). Participants will be re-assessed at 18 months to evaluate weight maintenance, bone mineral density, physical function, and other secondary measures. ClinicalTrials.gov Identifier: NCT02437643
A prediction model of delayed graft function in deceased donor for renal transplant: a multi-center study from China

Abstract Background Kidneys obtained from deceased donors increase the incidence of delayed graft function (DGF) after renal transplantation. Here we investigated the influence of the risk factors of donors with DGF, and developed a donor risk scoring system for DGF prediction. Methods This retrospective study was conducted in 1807 deceased kidney donors and 3599 recipients who received donor kidneys via transplants in 29 centers in China. We quantified DGF associations with donor clinical characteristics. A donor risk scoring system was developed and validated using an independent sample set. Results The incidence of DGF from donors was 19.0%. Six of the donor characteristics analyzed, i.e., age, cause of death, history of hypertension, terminal serum creatinine, persistence of hypotension, and cardiopulmonary resuscitation (CPR) time were risk factors for DGF. A 49-point scoring system of donor risk was established for DGF prediction and exhibited a superior degree of discrimination. External validation of DGF prediction revealed area under the receiver-operating characteristic (AUC) curves of 0.7552. Conclusions Our study determined the deceased donor risk factors related to DGF after renal transplantation pertinent to the Chinese cohort. The scoring system developed here had superior diagnostic significance and consistency and can be used by clinicians to make evidence-based decisions on the quality of kidneys from deceased donors and guide renal transplantation therapy.
Generation of avian-derived anti-B7-H4 antibodies exerts a blockade effect on the immunosuppressive response

For highly conserved mammalian protein, chicken is a suitable immune host to generate antibodies. Monoclonal antibodies have been successfully targeted with immunity checkpoint proteins as a means of cancer treatment; this treatment enhances tumor-specific immunity responses through immunoregulation. Studies have identified the importance of B7-H4 in immunoregulation and its use as a potential target for cancer treatment. High levels of B7-H4 expression are found in tumor tissues and are associated with adverse clinical and pathological characteristics. Using the phage display technique, this study isolated specific single-chain antibody fragments (scFvs) against B7-H4 from chickens. Our experiment proved that B7-H4 clearly induced the inhibition of T-cell activation. Therefore, use of anti-B7-H4 scFvs can effectively block the exhaustion of immunity cells and also stimulate and activate T-cells in peripheral blood mononuclear cells. Sequence analysis revealed that two isolated scFv S2 and S4 have the same VH complementarity-determining regions (CDRs) sequence. Molecule docking was employed to simulate the complex structures of scFv with B7-H4 to analyze the interaction. Our findings revealed that both scFvs employed CDR-H1 and CDR-H3 as main driving forces and had strong binding effects with the B7-H4. The affinity of scFv S2 was better because the CDR-L2 loop of the scFv S2 had three more hydrogen bond interactions with B7-H4. The results of this experiment suggest the usefulness of B7-H4 as a target for immunity checkpoints; the isolated B7-H4-specific chicken antibodies have the potential for use in future cancer immunotherapy applications.
Effects of tailored lateral wedge insoles on medial knee osteoarthritis based on biomechanical analysis: 12-week randomized controlled trial

Background: Lateral wedge insoles adjusted by biomechanical analysis may improve the condition of patients with medial knee osteoarthritis. Design: This is a prospective, randomized, controlled, single-blind clinical trial. Setting: The study was conducted in a biomechanics laboratory. Subjects: A total of 38 patients with medial knee osteoarthritis were allocated to either an experimental group (lateral wedge insoles) or a control group (neutral insoles). Interventions: Experimental group (n = 20) received an adjusted lateral wedge insole of 2, 4, 6, 8, or 10 degrees, after previous biomechanical analysis. Control group (n = 18) received a neutral insole (0 degrees). All patients used the insoles for 12 weeks. Main measures: Visual analogue scale, Knee Injury and Osteoarthritis Outcome Score questionnaire, biomechanical parameters: first and second peak of the external knee adduction moment and knee adduction angular impulse, and physical performance tests: 30-second sit-to-stand test, the 40-m fast-paced walk test, and the 12-step stair-climb test. Results: After 12 weeks, between-group differences did not differ significantly for pain intensity (−12.5 mm, (95% CI −29.4–4.4)), biomechanical parameters (p = 0.05), Knee Injury and Osteoarthritis Outcome Score, and physical performance tests, except on the Knee Injury and Osteoarthritis Outcome Score subscale other symptoms (p = 0.002; 13.8 points, (95% CI 5.6–22.0)). Conclusion: Tailored wedge insoles were no more effective at improving biomechanical or clinically meaningful outcomes than neutral insoles, except on symptoms. More participants from the experimental group reported they felt some improvement. However, these effects were minimal and without clinical significance.
Overweight is associated with better one-year survival in elderly patients after cardiac surgery: a retrospective analysis of the MIMIC-III database

Background The relationship of body mass index (BMI) to short- and long-term outcomes after cardiac surgery remains controversial, and the dose-response relationship between BMI and mortality in patients receiving cardiac surgery is unclear. Furthermore, the influence of age, concomitant disease, and types of surgery on the prognostic role of BMI has yet to be determined. Methods A retrospective cohort study with 6,473 adult patients receiving cardiac surgery was conducted using the Multiparameter Intelligent Monitoring in Intensive Care (MIMIC-III) database. Multivariate Cox proportional hazard analysis and multivariate logistic regression analysis were used to assess the association of BMI with 1-year and in-hospital mortality. Restricted cubic regression splines were used to evaluate the effect of BMI as a continuous variable and to determine appropriate cut points. Subgroup analyses were performed based on age, hypertension and types of surgery. Results The baseline characteristics of patients differed between BMI categories. On multivariable analysis, overweight patients (BMI 25–30 kg/m2) had a lower 1-year mortality [hazard ratio (HR) =0.660, 95% confidence interval (CI): 0.516–0.843, P=0.001] when compared with normal weight patients (BMI 18.5–25 kg/m2). For patients with BMI <30 kg/m2, each 1 kg/m2 BMI increase was independently associated with a significant decrease in the 1-year mortality risk (HR =0.936, 95% CI: 0.899–0.975, P=0.002), while in patients with BMI ≥30 kg/m2, an increase in BMI did not increase the 1-year mortality risk (HR =1.032, 95% CI: 0.998–1.067, P=0.064). Subgroup analyses suggested the protective effect of overweight on post-cardiac surgery survival was confined to patients with advanced age (>60 years), hypertension and those undergoing isolated coronary artery bypass grafting (CABG). Conclusions Overweight was associated with better 1-year survival in patients after cardiac surgery when compared to normal weight. The protective effect of overweight on post-cardiac surgery survival was confined to elderly patients (>60 years).
Sarcopenia is a Predictor for Adverse Clinical Outcome in Pediatric Inflammatory Bowel Disease

Supplemental Digital Content is available in the text ABSTRACT Objectives: Inflammatory bowel disease (IBD) has a high impact on nutritional status. Sarcopenia is related to higher risk of surgery and rescue therapy in adults with IBD; however, comparable data in pediatric populations are scarce. We evaluated muscle mass as a predictor of disease outcome in pediatric IBD. Methods: All pediatric IBD patients who underwent magnetic resonance enterography (MRE) during 2008 to 2019 were included. Muscle mass was assessed by measuring the area of the psoas muscle at the upper level of L3 on MRE. The psoas area divided by the body surface area (BSA) yielded the psoas index. Clinical and radiological data, including disease location, activity, course, and medications were documented. The control group included non-IBD children who underwent an MR imaging study. Results: We enrolled 101 IBD patients, 69 (68.3%) with Crohn disease (CD) and 32 (31.7%) with ulcerative colitis (UC) (mean age 15.03 ± 3.27 years). The psoas index was significantly lower in the IBD patients compared with the 87 controls (326 vs 528, respectively, P < 0.001). Patients with a psoas index in the lowest quartile had significantly higher risk for biologic therapy (multivariate analysis, hazard ratio [HR] = 12.1, P = 0.046) and disease exacerbation (HR = 9, P = 0.047) independently of body mass index, compared with patients with a psoas index in the uppermost quartile. Conclusions: Sarcopenia correlates with the radiological severity of pediatric IBD and serves as a predictor for adverse clinical disease outcome. Muscle mass measurement in MRE studies may serve as a possible marker for disease outcome in this population.
Indirect White Matter Pathways Are Associated With Treated Naming Improvement in Aphasia

Background White matter disconnection of language-specific brain regions associates with worse aphasia recovery. Despite a loss of direct connections, many stroke survivors may maintain indirect connections between brain regions. Objective To determine (1) whether preserved direct connections between language-specific brain regions relate to better poststroke naming treatment outcomes compared to no direct connections and (2) whether for individuals with a loss of direct connections, preserved indirect connections are associated with better treatment outcomes compared to individuals with no connections. Methods We computed structural whole-brain connectomes from 69 individuals with chronic left-hemisphere stroke and aphasia who completed a 3-week-long language treatment that was supplemented by either anodal transcranial direct current stimulation (A-tDCS) or sham stimulation (S-tDCS). We determined differences in naming improvement between individuals with direct, indirect, and no connections using 1-way analyses of covariance and multivariable linear regressions. Results Independently of tDCS modality, direct or indirect connections between the inferior frontal gyrus pars opercularis and angular gyrus were both associated with a greater increase in correct naming compared to no connections (P = .027 and P = .039, respectively). Participants with direct connections between the inferior frontal gyrus pars opercularis and middle temporal gyrus who received S-tDCS and participants with indirect connections who received A-tDCS significantly improved in naming accuracy. Conclusions Poststroke preservation of indirect white matter connections is associated with better treated naming improvement in aphasia even when direct connections are damaged. This mechanistic information can be used to stratify and predict treated naming recovery in individuals with aphasia.
Undergraduate Nursing Student Mental Health Clinical Experiences in Saudi Arabia: Findings From a Qualitative Study

BACKGROUND: Clinical experience is an important way of resolving preregistration challenges. Negative feelings toward pursuing a career in mental health nursing may be modified by well-structured practicums. AIMS: To explore nursing student perspectives of clinical practicums in mental health in Saudi Arabia for the purpose of enhancement of nurse education in mental health care. METHODS: This qualitative study used thematic analysis from semistructured focus group interviews of 20 female undergraduate nursing students. Inductive outcomes and emergent conceptual data were reviewed by investigators, doctoral prepared faculty peers, and members of the sample. NVivo 10.1 software was used to suggest conceptual groupings into themes based on inductive codes. RESULTS: The core theme—enhancement of mental health care skills—comprised four emerging subthemes, including the application of theory for clinical improvement, positive feelings, and motivation toward removal of discrimination and stigmatization, experience with apprehension, anxiety, fear, and stress, and therapeutic communication skills. DISCUSSION: Clinical placement in mental health-related practice may assist undergraduate nursing students in addressing anxiety and stress related to contacting patients, confronting stigmatizing and negative emotions, applying theoretical knowledge to clinical practice, having therapeutic communication skills, and enhancing overall professional experiences of nursing students. It is hoped that undergraduate clinical mental health placement will contribute valuable skills and viewpoints to nursing students who aim to enter professional practice in all areas and especially mental health.
Validity of Surrogate Endpoints and Their Impact on Coverage Recommendations: A Retrospective Analysis across International Health Technology Assessment Agencies

Background Surrogate endpoints (i.e., intermediate endpoints intended to predict for patient-centered outcomes) are increasingly common. However, little is known about how surrogate evidence is handled in the context of health technology assessment (HTA). Objectives 1) To map methodologies for the validation of surrogate endpoints and 2) to determine their impact on acceptability of surrogates and coverage decisions made by HTA agencies. Methods We sought HTA reports where evaluation relied on a surrogate from 8 HTA agencies. We extracted data on the methods applied for surrogate validation. We assessed the level of agreement between agencies and fitted mixed-effects logistic regression models to test the impact of validation approaches on the agency’s acceptability of the surrogate endpoint and their coverage recommendation. Results Of the 124 included reports, 61 (49%) discussed the level of evidence to support the relationship between the surrogate and the patient-centered endpoint, 27 (22%) reported a correlation coefficient/association measure, and 40 (32%) quantified the expected effect on the patient-centered outcome. Overall, the surrogate endpoint was deemed acceptable in 49 (40%) reports (k-coefficient 0.10, P = 0.004). Any consideration of the level of evidence was associated with accepting the surrogate endpoint as valid (odds ratio [OR], 4.60; 95% confidence interval [CI], 1.60–13.18, P = 0.005). However, we did not find strong evidence of an association between accepting the surrogate endpoint and agency coverage recommendation (OR, 0.71; 95% CI, 0.23–2.20; P = 0.55). Conclusions Handling of surrogate endpoint evidence in reports varied greatly across HTA agencies, with inconsistent consideration of the level of evidence and statistical validation. Our findings call for careful reconsideration of the issue of surrogacy and the need for harmonization of practices across international HTA agencies.