Miracle-dz/UniFAR-FTUs huggingface dataset:
Serum 25-Hydroxyvitamin D Concentrations at Birth in Children Screened for HLA-DQB1 Conferred Risk for Type 1 Diabetes

Abstract Context Vitamin D has several effects on the immune system that might be of relevance for the pathogenesis of type 1 diabetes (T1D). Objective To evaluate whether umbilical cord serum concentrations of 25-hydroxy-vitamin D (25[OH]D) differ in children developing either islet autoimmunity (IA) or overt T1D during childhood and adolescence. Design Umbilical cord serum samples from 764 children born from 1994 to 2004 with HLA-DQB1 conferred risk for T1D participating in the Type 1 Diabetes Prediction and Prevention Study were analyzed for 25(OH)D using an enzyme immunoassay. Setting DIPP clinics in Turku, Oulu, and Tampere University Hospitals, Finland. Participants Two hundred fifty children who developed T1D diabetes at a median age of 6.7 years (interquartile range [IQR] 4.0 to 10.1 years) and 132 additional case children who developed IA, i.e., positivity for multiple islet autoantibodies. Cases were matched for date of birth, gender, and area of birth with 382 control children who remained autoantibody negative. The median duration of follow up was 9.8 years (IQR 5.7 to 13.1 years). Main Outcome Measure The median 25(OH)D concentrations. Results The median 25(OH)D concentration in cord serum was low [31.1 nmol/L (IQR 24.0 to 41.8); 88% <50 nmol/L], but not statistically different between children who developed T1D or IA and their control groups (P = 0.70). The levels were associated mainly with geographical location, year and month of birth, age of the mother, and maternal intake of vitamin D during pregnancy. Conclusions The 25(OH)D concentrations at birth are not associated with the development of T1D during childhood.
Factors at de novo donor‐specific antibody initial detection associated with allograft loss: a multicenter study

We aimed to evaluate patient factors including nonadherence and viral infection and de novo donor‐specific antibody (dnDSA) characteristics [total immunoglobulin G (IgG), C1q, IgG3, and IgG4] as predictors of renal allograft failure in a multicenter cohort with dnDSA. We performed a retrospective observational study of 113 kidney transplant recipients with dnDSA and stored sera for analysis. Predictors of death‐censored allograft loss were assessed by Cox proportional modeling. Death‐censored allograft survival was 77.0% (87/113) during a median follow‐up of 2.2 (IQR 1.2–3.7) years after dnDSA detection. Predictors of allograft failure included medication nonadherence [HR 6.5 (95% CI 2.6–15.9)], prior viral infection requiring immunosuppression reduction [HR 5.3 (95% CI 2.1–13.5)], IgG3 positivity [HR 3.8 (95% CI 1.5, 9.3)], and time post‐transplant (years) until donor‐specific antibody (DSA) detection [HR 1.2 (95% CI 1.0, 1.3)]. In the 67 patients who were biopsied at dnDSA detection, chronic antibody‐mediated rejection [HR 11.4 (95% CI 2.3, 56.0)] and mixed rejection [HR 7.4 (95% CI 2.2, 24.8)] were associated with allograft failure. We conclude that patient factors, including a history of viral infection requiring immunosuppression reduction or medication nonadherence, combined with DSA and histologic parameters must be considered to understand the risk of allograft failure in patients with dnDSA.
No evidence so far of a major role of AKT1 and GSK3B in the pathogenesis of antipsychotic‐induced tardive dyskinesia

AKT1 and GSK3B take part in one of the intracellular cascades activated by the D2 dopamine receptor (DRD2). This receptor is antagonized by antipsychotics and plays a role in the pathogenesis of antipsychotic‐induced tardive dyskinesia (TD). The present study investigated association of several polymorphisms in the two candidate genes, AKT1 and GSK3B, with TD in antipsychotic‐treated patients with schizophrenia.
Prevalence of depressive symptoms and associated factors among adolescents living with HIV/AIDS in South Western Uganda

ABSTRACT Adolescents living with HIV (ALHIV) are prone to depression, which can have detrimental effects including disease progression, poor treatment adherence and mortality. We aimed to determine the prevalence of depressive symptoms and their associated factors among ALHIV in Uganda. We conducted a cross-sectional survey among ALHIV (10–19 years) attending urban and rural clinics in Mbarara, Uganda between March and May 2017. Presence of depressive symptoms was assessed using the Centre for Epidemiological Studies’ Depression scale. We interviewed 336 adolescents with a median age of 13 years, 62% of whom were female. A third (37%) had disclosed their HIV/AIDS status and 13% were sexually active. Overall, 154 (∼46%, [95% CI: 40.5–51.2]) had depressive symptoms. On bivariate analysis, the odds of having depressive symptoms were higher among adolescents who were ≥ 15 years, had disclosed HIV status, traveled >30 min for routine care and had risky sexual practices. On multiple variable analysis, only travel time to the clinic of >30 min was independently associated with depressive symptoms (AOR = 1.6 [95% CI: 1.02–2.7]). With the high prevalence of depressive symptoms among ALHIV in Uganda, screening and prompt treatment of depression should be incorporated within their routine care.
Effects of skeletal unloading on the antibody repertoire of tetanus toxoid and/or CpG treated C57BL/6J mice

Spaceflight affects the immune system, but the effects on the antibody repertoire, responsible for humoral immunity, has not been well explored. In particular, the complex gene assembly and expression process; including mutations, might make this process vulnerable. Complementarity determining region 3 (CDR3), composed of parts of the V-(D-)J-gene segments, is very important for antigen binding and can be used as an important measure of variability. Skeletal unloading, and the physiological effects of it, parallel many impacts of space flight. Therefore, we explored the impact of skeletal unloading using the antiorthostatic suspension (AOS) model. Animals were experimentally challenged with tetanus toxoid (TT) and/or the adjuvant CpG. Blood was analyzed for anti-TT antibody and corticosterone concentrations. Whole spleen tissue was prepared for repertoire characterization. AOS animals showed higher levels of corticosterone levels, but AOS alone did not affect anti-TT serum antibody levels. Administration of CpG significantly increased the circulating anti-TT antibody concentrations. AOS did alter constant gene usage resulting in higher levels of IgM and lower levels of IgG. CpG also altered constant gene region usage increasing usage of IgA. Significant changes could be detected in multiple V-, D-, and J-gene segments in both the heavy and light chains in response to AOS, TT, and CpG treatments. Analysis of class-switched only transcripts revealed a different pattern of V-gene segment usage than detected in the whole repertoire and also showed significant alterations in gene segment usage after challenge. Alterations in V/J pairing were also detected in response to challenge. CDR3 amino acid sequence overlaps were similar among treatment groups, though the addition of CpG lowered overlap in the heavy chain. We isolated 3,045 whole repertoire and 98 potentially TT-specific CDR3 sequences for the heavy chain and 569 for the light chain. Our results demonstrate that AOS alters the repertoire response to challenge with TT and/or CpG.
Astragaloside IV ameliorates endoplasmic reticulum stress-induced apoptosis of Aβ25-35-treated PC12 cells by inhibiting the p38 MAPK signaling pathway

Endoplasmic reticulum stress (ERS) serves a vital role in the pathological development of Alzheimer's disease (AD). ERS can promote programmed cell death (apoptosis) during AD; however, the specific molecular mechanisms that lead to ERS remain unclear. It is very important that a drug for the treatment of AD is identified. Our previous studies indicated that astragaloside IV (AST IV) has anti-inflammatory effects and helps cells resist oxidative stress. In the present study, western blotting and reverse transcription semi-quantitative polymerase chain reaction were used to detect protein and mRNA expression levels, flow cytometry was used to measure intracellular reactive oxygen species (ROS) levels, and superoxide dismutase (SOD) and malondialdehyde (MDA) activity was detected using commercially available kits. The results demonstrated that SOD activity was decreased, and MDA content, ROS levels, and the expression levels of p38 mitogen-activated protein kinase (MAPK) and ERS-associated proteins, including binding immunoglobulin protein/glucose-regulated protein and growth arrest- and DNA damage -inducible gene 153/C/EBP homologous protein, were increased in amyloid β (Aβ)25-35-treated PC12 cells. Furthermore, to investigate the role of p38 MAPK and the effects of AST IV in an in vitro model of AD, SB203580, a p38 MAPK signaling pathway inhibitor, and AST IV were administered to Aβ25-35-treated PC12 cells. The results revealed that AST IV protected the cells against AD. This effect may be caused by decreases in ROS levels, which may inhibit the p38 MAPK signaling pathway and thereby suppress ERS in Aβ25-35-treated PC12 cells.
Building the Arrow of Time… Over Time: A Sequence of Brain Activity Mapping Imagined Events in Time and Space.

When moving, the spatiotemporal unfolding of events is bound to our physical trajectory, and time and space become entangled in episodic memory. When imagining past or future events, or being in different geographical locations, the temporal and spatial dimensions of mental events can be independently accessed and manipulated. Using time-resolved neuroimaging, we characterized brain activity while participants ordered historical events from different mental perspectives in time (e.g., when imagining being 9 years in the future) or in space (e.g., when imagining being in Cayenne). We describe 2 neural signatures of temporal ordinality: an early brain response distinguishing whether participants were mentally in the past, the present or the future (self-projection in time), and a graded activity at event retrieval, indexing the mental distance between the representation of the self in time and the event. Neural signatures of ordinality and symbolic distances in time were distinct from those observed in the homologous spatial task: activity indicating spatial order and distances overlapped in latency in distinct brain regions. We interpret our findings as evidence that the conscious representation of time and space share algorithms (egocentric mapping, distance, and ordinality computations) but different implementations with a distinctive status for the psychological "time arrow. "
Work-Related Musculoskeletal Symptoms among Loggers in the Ark-La-Tex Region

ABSTRACT Background: The U.S. logging sector is among the most dangerous industrial sectors, with high fatality and non-fatal injury rates. Limited research has addressed work-related musculoskeletal disorders among logging machine operators (LMOs). The purpose of this study was to estimate the 12-month prevalence of musculoskeletal symptoms and the associated work-related risk factors among LMOs in the Arkansas, Louisiana, and Texas (Ark-La-Tex) logging region. Methods: A self-administered 93-item questionnaire with six different sections: (1) demographics, (2) lifestyle and medical background, (3) work experience, (4) job training, (5) occupational heat-related stress, and (6) occupational injuries and MSS was administered to LMOs (n = 88) using Qualtrics Mobile Survey Software®. Poisson regression models were used to estimate crude prevalence ratios (PR), adjusted PR [aPR], and corresponding 95% confidence intervals (95% CI). Results: Regarding organizational, ergonomic, and handling equipment occupational factors and 12-month MSS prevalence, the adjusted model controlled for age, BMI, smoking status, and drinking status. For organizational, the most problematic factors for the lower back were performing a task over and over (63.2%) and working very fast, for short periods (60.0%). For ergonomics, the most problematic factor for the lower extremities was awkward or cramped conditions (58.1%) and for the lower back was bending/twisting back awkward (55.9%). Last, for handling equipment, the most problematic for both the lower back and lower extremities was handling or grasping small objects (57.1%). Conclusion: Our findings revealed associations between work-related MSS and specific job factors (e.g., organizational, ergonomic, handling equipment, etc.), extreme environmental conditions or environmental, and personal risk factors. In particular, study findings suggest lower back and lower extremities MSS are associated with the a majority of job-related risk factors, lower extremities with extreme environmental conditions, and neck and upper back with personal risk factors.
Impact of adjuvant treatment on outcome in high-risk early-stage endometrial cancer: a retrospective three-center study

Objective High grade and non-endometrioid endometrial cancers carry a poor prognosis, and the lack of randomized prospective data has led to a wide range of practice regarding adjuvant therapy. The objective of this study was to evaluate the outcomes of different treatment strategies in patients with high-risk, early-stage endometrial cancer. Methods Patients with high-grade endometrioid, serous endometrial cancer and carcinosarcoma diagnosed between 2000 and 2012 were identified from databases in three gynecologic oncology divisions, in Toronto and in Israel. Adjuvant treatment practices differed across the centers, creating a heterogeneous cohort. A comparison of stage I patients stratified by adjuvant treatment was undertaken. Log-rank tests and Cox proportional hazards models were employed to compare recurrence and survival across treatment groups. Results 490patients with high risk endometrial cancer were identified, among them 213 patients with stage I disease. Israeli patients received more chemotherapy (41% vs 10% in stage I disease; P<0.001) than patients in Toronto. Chemotherapy was not associated with improved disease-free, disease-specific or overall survival, nor was it associated with fewer distant recurrences (50% vs 54%). Radiation was also not associated with improved recurrence or survival, nor did it affect the pattern of recurrence. On Cox multivariable analysis, neither radiation treatment nor chemotherapy were significantly associated with outcome (HR for recurrence, 0.72 for pelvic radiation (P=0.46) and 1.99 for chemotherapy (P=0.09); HR for death, 0.67 for pelvic radiation (P=0.29) and 1.03 for chemotherapy (P=0.94)). Conclusions In this retrospective analysis, neither adjuvant radiation nor chemotherapy were associated with improved outcome in stage I, high risk endometrial cancer.
Occlusion of anion-binding exosite 2 in meizothrombin explains its impaired ability to activate factor V

The proteolytic conversion of factor V to factor Va is central for amplified flux through the blood coagulation cascade. Heterodimeric factor Va is produced by cleavage at three sites in the middle of factor V by thrombin, yielding an N terminus–derived heavy chain and a C terminus–derived light chain. Here, we show that light chain formation resulting from the C-terminal cleavage is the rate-limiting step in the formation of fully cleaved Va. This rate-limiting step also corresponded to and was sufficient for the ability of cleaved factor V to bind Xa and assemble into the prothrombinase complex. Meizothrombin, the proteinase intermediate in thrombin formation, cleaves factor V more slowly than does thrombin, resulting in a pronounced defect in the formation of the light chain. A ∼100-fold reduced rate of meizothrombin-mediated light chain formation by meizothrombin corresponded to equally slow production of active cofactor and an impaired ability to amplify flux through the coagulation cascade initiated in plasma. We show that this defect arises from the occlusion of anion-binding exosite 2 in the catalytic domain by the covalently retained propiece in meizothrombin. Our findings provide structural insights into the prominent role played by exosite 2 in the rate-limiting step of factor V activation. They also bear on how factor V is converted into a cofactor capable of assembling into prothrombinase.
Clinicopathologic and prognostic significance of tumor-infiltrating CD8+ T cells in patients with hepatocellular carcinoma

Background: In patients with hepatocellular carcinoma (HCC), the clinicopathologic and prognostic roles of tumor-infiltrating CD8+ T cells for survival are still controversial. A meta-analysis was performed to resolve this issue. Methods: We identified studies from PubMed, Embase, and the Cochrane Library to evaluate the clinicopathologic and prognostic value of tumor-infiltrating CD8+ T cells in patients with HCC. A meta-analysis was conducted to estimate clinicopathologic characteristics, overall survival (OS), and disease-free survival. The hazard ratio (HR) and 95% confidence interval (CI) were calculated employing fixed-effect or random-effect models depending on the heterogeneity of the included trials. Results: A total of 3509 patients from 21 observational studies were enrolled. The meta-analysis revealed that high levels of intratumoral CD8+ tumor-infiltrating lymphocytes (TILs) were associated with better OS (OS; HR = 0.676, P = .001) and disease-free survival (disease-free survival [DFS]; HR = 0.712, P = .002). The pooled analysis also demonstrated high density of infiltration of CD8+ TILs in margin of tumor (MT) was statistically significant associated with better OS (HR = 0.577; P <.001). Moreover, the patients with low CD8+ TILs infiltration had negative HBSAg (OR = 1.67, P = .02), large tumor size (OR = 1.74, P <.01), and later TNM stage (OR = 1.70, P <.01). Conclusions: Our findings suggested that low levels of CD8+ TILs predict large tumor size, later TNM stage and might be a promising prognostic factor of HCC especially for Asian patients. High-quality randomized controlled trials are needed to determine if CD8+ TILs could serve as targets for immunotherapy in hepatocellular carcinoma.
Bros Will Be Bros? The Effect of Fraternity Membership on Perceived Culpability for Sexual Assault

To examine the link between fraternity membership and sexual assault perpetration, we used an experimental design to assess the role of perceptions in an ambiguous sexual assault scenario. Undergraduates (N = 408) were randomly assigned to either an experimental group where the perpetrator is a fraternity member or a control group where no fraternity information is given. Males rated perpetrators as less guilty and victims as more culpable when the perpetrator was a fraternity member, suggesting that sexual violence may be reinforced among fraternity members as they are both more likely to perpetrate sexual assault and less likely to be blamed.
Power-Type Varying-Parameter RNN for Solving TVQP Problems: Design, Analysis, and Applications

Many practical problems can be solved by being formulated as time-varying quadratic programing (TVQP) problems. In this paper, a novel power-type varying-parameter recurrent neural network (VPNN) is proposed and analyzed to effectively solve the resulting TVQP problems, as well as the original practical problems. For a clear understanding, we introduce this model from three aspects: design, analysis, and applications. Specifically, the reason why and the method we use to design this neural network model for solving online TVQP problems subject to time-varying linear equality/inequality are described in detail. The theoretical analysis confirms that when activated by six commonly used activation functions, VPNN achieves a superexponential convergence rate. In contrast to the traditional zeroing neural network with fixed design parameters, the proposed VPNN has better convergence performance. Comparative simulations with state-of-the-art methods confirm the advantages of VPNN. Furthermore, the application of VPNN to a robot motion planning problem verifies the feasibility, applicability, and efficiency of the proposed method.
Aging Expectations and Attitudes: Associations With Types of Older Adult Contact

Objectives: To evaluate the role of contact with older adults in explaining expectations about aging and attitudes toward own aging. Method: A representative sample of 3,026 U.S. adults aged 30–89 years completed a survey online or by telephone. The survey assessed types of contact with older adults, anticipated need for help during aging, and attitudes toward their own aging. Results: Relative to older adults’ (65+ years) need for help with finances, activities of daily living, social support, and health care during aging, 30- to 64-year-old adults overestimated their expected need for help. Contact with dependent older adults was associated with greater overestimation. Diverse types of contact with older adults were associated with increased positivity toward one’s own aging. Discussion: Aging expectations may be ameliorated by exposure to diverse exemplars of aging. Future research should quantify effects of exposure types on both negative and positive attitudes toward own aging.
Prevalence of Anemia in Children from Latin America and the Caribbean and Effectiveness of Nutritional Interventions: Systematic Review and Meta–Analysis

Anemia affects 1.62 billion people worldwide. Latin America and the Caribbean (LAC) comprise several developing countries where children are a population at risk. This systematic review and meta-analysis aimed to estimate the prevalence of anemia in this population. Electronic databases, reference lists, and websites of health ministries were searched until December 2018. Stratified analyses were performed using RevMan5.3 to estimate the overall prevalence of anemia in preschool and school-age children. The effectiveness of nutritional interventions was also evaluated. We included 61 studies from the 917 reviewed, which included 128,311 preschool- and 38,028 school-age children from 21 LAC countries. The number of anemic children was 32.93% and 17.49%, respectively, demonstrating a significant difference according to age (p < 0.01). No difference was observed by gender and only school-age children from low/very low socioeconomic status (SES) (25.75%) were more prone to anemia than those from middle SES (7.90%). It was not a concern in the Southern Cone but constituted a serious public health problem in the Latin Caribbean. Nutritional interventions reduced the prevalence from 45% to 25% (p < 0.01). Anemia is still a public health problem for children in LAC countries. National surveys should include school-age children. Further nutritional interventions are required to control anemia.
Human trisomy 21 fibroblasts rescue methotrexate toxic effect after treatment with 5‐methyl‐tetrahydrofolate and 5‐formyl‐tetrahydrofolate

Trisomy 21 causes Down syndrome (DS), the most common human genetic disorder and the leading genetic cause of intellectual disability. The alteration of one‐carbon metabolism was described as the possible metabolic cause of the intellectual disability development in subjects with DS. One of the biochemical pathways involved in the one‐carbon group transfer is the folate cycle. The cytotoxic drug methotrexate (MTX) is a folic acid (FA) analogue which inhibits the activity of dihydrofolate reductase enzyme involved in the one‐carbon metabolic cycle. Trisomy 21 cells are more sensitive to the MTX effect than euploid cells, and in 1986 Jérôme Lejeune and Coll. demonstrated that MTX was twice as toxic in trisomy 21 lymphocytes than in control cells. In the present work, the rescue effect on MTX toxicity mediated by FA and some of its derivatives, tetrahydrofolate (THF), 5‐formyl‐THF, and 5‐methyl‐THF, in both normal and trisomy 21 skin fibroblast cells, was evaluated. A statistically significant rescue effect was obtained by 5‐formyl‐THF, 5‐methyl‐THF, and their combination, administered together with MTX. In conclusion, trisomy 21 fibroblast cell lines showed a good response to the rescue effects of 5‐formyl‐THF and 5‐methyl‐THF on the MTX toxicity almost as normal cell lines.