Miracle-dz/UniFAR-FTUs huggingface dataset:
A large case-control study on vaccination as risk factor for multiple sclerosis

Objective To investigate the hypothesis that vaccination is a risk factor for multiple sclerosis (MS) by use of German ambulatory claims data in a case-control study. Methods Using the ambulatory claims data of the Bavarian Association of Statutory Health Insurance Physicians covering 2005–2017, logistic regression models were used to assess the relation between MS (n = 12,262) and vaccinations in the 5 years before first diagnosis. Participants newly diagnosed with Crohn disease (n = 19,296) or psoriasis (n = 112,292) and participants with no history of these autoimmune diseases (n = 79,185) served as controls. Results The odds of MS were lower in participants with a recorded vaccination (odds ratio [OR] 0.870, p < 0.001 vs participants without autoimmune disease; OR 0.919, p < 0.001 vs participants with Crohn disease; OR 0.973, p = 0.177 vs participants with psoriasis). Lower odds were most pronounced for vaccinations against influenza and tick-borne encephalitis. These effects were consistently observed for different time frames, control cohorts, and definitions of the MS cohort. Effect sizes increased toward the time of first diagnosis. Conclusions Results of the present study do not reveal vaccination to be a risk factor for MS. On the contrary, they consistently suggest that vaccination is associated with a lower likelihood of being diagnosed with MS within the next 5 years. Whether this is a protective effect needs to be addressed by future studies.
Meta‐analysis of unplanned readmission to hospital post‐appendectomy: an opportunity for a new benchmark

Appendicitis is the most common cause of acute abdominal pain requiring surgical intervention. While many studies report readmission, a meta‐analysis of readmission post‐appendectomy has not been published. This meta‐analysis was undertaken to determine rates and predictors of hospital readmission following appendectomy and to potentially provide a metric benchmark.
Epidemiology of amyotrophic lateral sclerosis: an update of recent literature

Purpose of review The cause of amyotrophic lateral sclerosis (ALS) remains unknown for most of the patients with the disease. Epidemiologic studies can help describe disease burden and examine its potential risk factors, providing thereby evidence base for future mechanistic studies. With this review, we aimed to provide a summary of epidemiologic studies published during the past 18 months, which studied the incidence and risk factors for ALS. Recent findings An increasing incidence and prevalence of ALS continue to be reported from different parts of the world. Several previously studied risk factors are confirmed as causally related to ALS by Mendelian randomization analysis. The previously known prognostic indicators for ALS appear to be the same across populations. Summary Provided with the increasing number of patients diagnosed with ALS and the improved societal awareness of the disease, more resources should be allocated to the research and care of ALS. Population-based studies, especially population-based disease registers, should be the priorities in ALS research, and more data from outside Europe are needed in gaining a better global perspective of the disease.
Cardiovascular effect of discontinuing statins for primary prevention at the age of 75 years: a nationwide population-based cohort study in France

Abstract Aims The role of statin therapy in primary prevention of cardiovascular disease in persons older than 75 years remains a subject of debate with little evidence to support or exclude the benefit of this treatment. We assessed the effect of statin discontinuation on cardiovascular outcomes in previously adherent 75-year-olds treated for primary prevention. Methods and results A population-based cohort study using French national healthcare databases was performed, studying all subjects who turned 75 in 2012–14, with no history of cardiovascular disease and with a statin medication possession ratio ≥80% in each of the previous 2 years. Statin discontinuation was defined as three consecutive months without exposure. The outcome was hospital admission for cardiovascular event. The hazard ratio comparing statin discontinuation with continuation was estimated using a marginal structural model adjusting for both baseline and time-varying covariates (cardiovascular drug use, comorbidities, and frailty indicators). A total of 120 173 subjects were followed for an average of 2.4 years, of whom 17 204 (14.3%) discontinued statins and 5396 (4.5%) were admitted for a cardiovascular event. The adjusted hazard ratios for statin discontinuation were 1.33 [95% confidence interval (CI) 1.18–1.50] (any cardiovascular event), 1.46 (95% CI 1.21–1.75) (coronary event), 1.26 (95% CI 1.05–1.51) (cerebrovascular event), and 1.02 (95% CI 0.74–1.40) (other vascular event). Conclusion Statin discontinuation was associated with a 33% increased risk of admission for cardiovascular event in 75-year-old primary prevention patients. Future studies, including randomized studies, are needed to confirm these findings and support updating and clarification of guidelines on the use of statins for primary prevention in the elderly.
Optimism/hope associated with low anxiety in patients with advanced heart disease controlling for standardized cardiac confounders

Anxiety is an under-investigated comorbidity in heart disease patients. Optimism/hope is a character strength that indicates confidence or favorable expectation about the future. Previous research has consistently reported optimal health outcomes among optimists. However, many studies have lacked adjustment for medical confounders and/or used small clinical samples. To bridge this gap, we tested the hypothesis that optimism/hope was inversely related to anxiety in 400+ patients with advanced heart disease during the stressful waiting period prior to open-heart surgery. The findings supported the hypothesis after controlling for general health, illness impact, behavioral risks, and cardiac medical indices used by surgeons.
Exploring Pedagogical Foundations of Existing Virtual Reality Educational Applications: A Content Analysis Study

New virtual reality (VR) applications for education appear frequently in the marketplace but rarely contain explicit pedagogies. The research objective of this study was to identify and categorize principles and practices of pedagogy that are evident but not articulated in selected VR applications for education. Analysis of public content for the VR applications showed most were experiential while others were categorized as discovery learning, constructivism, situated cognition, direct instruction, or unclassified approaches. Educators and VR designers could use explicit pedagogical frameworks to support faculty development, construct extended, and congruent curricular options that stimulate reflections, build insights, and insure innovative and measurable outcomes.
Mapping the open education landscape: citation network analysis of historical open and distance education research

The term open education has recently been used to refer to topics such as Open Educational Resources (OERs) and Massive Open Online Courses (MOOCs). Historically its roots lie in civil approaches to education and open universities, but this research is rarely referenced or acknowledged in current interpretations. In this article the antecedents of the modern open educational movement are examined, as the basis for connecting the various strands of research. Using a citation analysis method the key references are extracted and their relationships mapped. This work reveals eight distinct sub-topics within the broad open education area, with relatively little overlap. The implications for this are discussed and methods of improving inter-topic research are proposed.
Bayesian Estimation of Past Population Dynamics in BEAST 1.10 Using the Skygrid Coalescent Model

Abstract Inferring past population dynamics over time from heterochronous molecular sequence data is often achieved using the Bayesian Skygrid model, a nonparametric coalescent model that estimates the effective population size over time. Available in BEAST, a cross-platform program for Bayesian analysis of molecular sequences using Markov chain Monte Carlo, this coalescent model is often estimated in conjunction with a molecular clock model to produce time-stamped phylogenetic trees. We here provide a practical guide to using BEAST and its accompanying applications for the purpose of drawing inference under these models. We focus on best practices, potential pitfalls, and recommendations that can be generalized to other software packages for Bayesian inference. This protocol shows how to use TempEst, BEAUti, and BEAST 1.10 (http://beast.community/; last accessed July 29, 2019), LogCombiner as well as Tracer in a complete workflow.
Signal coordination before, during, and after stomatal closure in response to drought stress.

Signal coordination in response to changes in water availability remains unclear, as does the role of embolism events in signaling drought stress. We exposed sunflowers to two drought treatments of varying intensity while simultaneously monitoring changes in stomatal conductance, acoustic emissions (AE), turgor pressure, surface-level electrical potential, organ-level water potential, and leaf abscisic acid (ABA) concentration. Leaf, stem, and root xylem vulnerability to embolism were measured with the single vessel injection technique. In both drought treatments, we found that AE events and turgor changes preceded the onset of stomatal closure, while electrical surface potentials shifted concurrently with stomatal closure. Leaf-level ABA concentration did not change until after stomata were closed. Roots and petioles were equally vulnerable to drought stress based on the single vessel injection technique. However, anatomical analysis of the xylem indicated that the increased AE events were not a result of xylem embolism formation. Additionally, roots and stems never reached a xylem pressure threshold that would initiate runaway embolism throughout the entire experiment. We conclude that stomatal closure was not embolism driven, but rather changes in leaf turgor were the hydraulic signal that most closely correlated with the onset of stomatal closure. This article is protected by copyright. All rights reserved.
Is valve-sparing root replacement a safe option in acute type A aortic dissection? A systematic review and meta-analysis.

OBJECTIVES There are conflicting views regarding the status of valve-sparing root replacement (VSRR) as a proper treatment for acute type A aortic dissection (AAAD). Our goal was to compare the early and late outcomes of VSRR versus those of the Bentall procedure in patients with AAAD. METHODS We performed a systematic review and meta-analysis of 9 studies to compare the outcomes of VSRR with those of the Bentall procedure in patients with AAAD. We focused on the following issues: early and late mortality rates, re-exploration, thromboembolization/bleeding events, infective endocarditis and reintervention rates. RESULTS A total of 706 patients with AAAD who underwent aortic root surgery were analysed; 254 patients were treated with VSRR and 452 with the Bentall procedure. VSRR was associated with a reduced risk of early death [odds ratio (OR) 0.34; 95% confidence interval (CI) 0.21-0.57] and late death (OR 0.34; 95% CI 0.21-0.57) compared with the Bentall procedure. No statistically significant difference was observed between the VSRR and Bentall groups with pooled ORs (OR 0.77; 95% CI 0.47-1.27, OR 0.61; 95% CI 0.32-1.18 and OR 0.71; 95% CI 0.23-2.15) for re-exploration, thromboembolization/bleeding and postoperative infective endocarditis, respectively. An increased risk of reintervention was observed for the VSRR compared to the Bentall group (OR 3.79; 95% CI 1.27-11.30). The pooled rate of reintervention incidence was 1.6% (95% CI 0.0-3.7%) and 0.4% (95% CI 0.0-1.3%) for the VSRR and the Bentall groups, respectively. CONCLUSIONS VSRR in patients with AAAD can be performed in experienced centres with excellent short- and long-term outcomes compared to those with the Bentall procedure and thus should be recommended especially for active young patients.
Hierarchical Structure in Sequence Processing: How to Measure It and Determine Its Neural Implementation

Abstract In many domains of human cognition, hierarchically structured representations are thought to play a key role. In this paper, we start with some foundational definitions of key phenomena like “sequence” and “hierarchy," and then outline potential signatures of hierarchical structure that can be observed in behavioral and neuroimaging data. Appropriate behavioral methods include classic ones from psycholinguistics along with some from the more recent artificial grammar learning and sentence processing literature. We then turn to neuroimaging evidence for hierarchical structure with a focus on the functional MRI literature. We conclude that, although a broad consensus exists about a role for a neural circuit incorporating the inferior frontal gyrus, the superior temporal sulcus, and the arcuate fasciculus, considerable uncertainty remains about the precise computational function(s) of this circuitry. An explicit theoretical framework, combined with an empirical approach focusing on distinguishing between plausible alternative hypotheses, will be necessary for further progress.
Predisposing factors for bacterial mastitis in ewes.

Objective of this review paper is the appraisal of predisposing factors for bacterial mastitis in ewes. Factors that predispose ewes to mastitis can be classified into non-animal-related factors (environmental and climatological factors, housing, nutrition, milking practices) and animal-related factors (anatomic, genetic, litter size - ethological factors, number and stage of lactation period, health problems). There are clear management - environment - animal interactions in mastitis development in ewes, which underline its multi-factorial nature. Research and studies regarding risk factors are important, in order to develop strategies for their elimination, control or correction. Control measures for bacterial mastitis, which attempt to eliminate predisposing factors for infection, can thus be developed and implemented. This article is protected by copyright. All rights reserved.
Downregulated LINC00460 inhibits cell proliferation and promotes cell apoptosis in prostate cancer.

OBJECTIVE LINC00460 has been confirmed to contribute to cancer development. However, the role and function of LINC00460 in prostate cancer is not identified. The purpose of this study was to evaluate the expression and effect of LINC00460 on prostate cancer cell malignant behaviors. PATIENTS AND METHODS The expression of LINC00460 in cancer tissues and cell lines were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) assay. The LINC00460 expression was downregulated by siRNA. The cell counting kit-8 (CCK-8) assay was used to detect cell proliferation. The cell migration and invasion were detected by migration and Matrigel invasion assays. The Western blot assay was used to detect the altered expression levels of Ki67, Cyclin D1, PI3K, p-AKT, T-AKT, Bcl2, and Bax. RESULTS LINC00460 was increased in human prostate cancer tissues and cell lines. LINC00460 high expression was related to Tumor Size (T1-T2/T3-T4; p=0.004), and high Gleason Score (≤8/>8, p=0.000). Downregulation of LINC00460 by siRNA could inhibit cancer cell proliferation and decreased Ki67 and Cyclin D1 expression. Meanwhile, downregulation of LINC00460 promoted apoptosis of cell lines and was related to PI3K/AKT pathway. CONCLUSIONS LINC00460 could regulate cell proliferation and cell apoptosis, which might be a novel marker in prostate cancer.
FAME 3: Predicting the Sites of Metabolism in Synthetic Compounds and Natural Products for Phase 1 and Phase 2 Metabolic Enzymes

In this work we present the third generation of FAst MEtabolizer (FAME 3), a collection of extra trees classifiers for the prediction of sites of metabolism (SoMs) in small molecules such as drugs, drug-like compounds, natural products, agrochemicals and cosmetics. FAME 3 was derived from the MetaQSAR database (J Med Chem 2018, 61, 1019-1030), a recently published data resource on xenobiotic metabolism that contains more than 2,100 substrates annotated with more than 6,300 experimentally confirmed SoMs related to redox reactions, hydrolysis and other non-redox reactions, and conjugation reactions. In tests with holdout data, FAME 3 models reached competitive performance, with Matthews correlation coefficients (MCCs) ranging from 0.50 for a global model covering phase 1 and phase 2 metabolism, to 0.75 for a focused model for phase 2 metabolism. A model focused on cytochrome P450 metabolism yielded an MCC of 0.57. Results from case studies with several synthetic compounds, natural products and natural product derivatives demonstrate the agreement between model predictions and literature data even for molecules with structural patterns clearly distinct from those present in the training data. The applicability domains of the individual models were estimated by a new, atom-based distance measure ("FAMEscore") that is based on a nearest neighbor search in the space of atom environments. FAME 3 is available as a self-contained Java software package, free for academic and non-commercial research.
Protocol for a prospective observational study on the association of variables obtained by contrast-enhanced ultrasonography and sepsis-associated acute kidney injury

Introduction Sepsis commonly results in acute kidney injury (AKI), whereas about 50% of AKI cases are due to sepsis. Sepsis-associated acute kidney injury (SA-AKI) increases morbidity and mortality especially among critically ill patients. This study aims to monitor renal microcirculation perfusion during sepsis using contrast-enhanced ultrasonography (CEUS), and to explore whether CEUS is useful for predicting the development of SA-AKI. Methods and analysis This prospective observational study will enrol patients who were diagnosed with sepsis-3 definition. The total of septic or septic shock patients were stratified into AKI (including stages 1, 2 and 3) and non-AKI groups according to Kidney Disease Improving Global Outcomes criteria on days 0, 1, 2 and 7 after admission to the emergency intensive care unit, meanwhile, the CEUS technique will be performed to monitor renal microcirculation perfusion. A multivariable model including all CEUS variables were expected to create for predicting the development of AKI during sepsis. Ultrasonography results, demographic information, therapeutic interventions, survival outcomes, laboratory and other clinical datas will also be collected for further analysis. Ethics and dissemination The study protocol was approved on 2 August 2017 by the Ethics Committee of Sir Run Run Shaw Hospital (Zhejiang University Medical College) (approval number: 2016C91401). The results will be published in a peer-reviewed journal and shared with the worldwide medical community within 2 years after the start of the recruitment. Trial registration number ISRCTN14728986
Pregnancy level of estradiol attenuated virus-specific humoral immune response in H5N1-infected female mice despite inducing anti-inflammatory protection

ABSTRACT Estradiol, a major female steroid produced during pregnancy, has been reported to protect ovariectomized animals against H1N1 influenza infections via its anti-inflammatory effects. However, it remains unclear why pregnant women with high gestational estradiol levels are highly susceptible to influenza infections. This study was aimed to investigate the effects of pregnancy level of estradiol on female immunity against H5N1 infection in Balb/c mice. A sex-dependent susceptibility to H5N1 infection (higher morbidity and higher mortality) was observed in both pregnant and non-pregnant female mice as compared to male mice. Subcutaneous implantation of estradiol pellets increased serum estradiol concentrations of non-pregnant female mice to the pregnancy level. These mice were protected from H5N1 infection through downregulation of pulmonary pro-inflammatory cytokines. However, the production of virus-specific antibodies after infection was significantly delayed in estradiol-implanted mice when compared to placebos. Virus-specific IgG-secreting and IL-4-secreting cells were also reduced in estradiol-implanted mice. Similarly, lower antibody titers to seasonal vaccine antigens were found in pregnant women as compared to non-pregnant females without hormone usage. Our results indicate that estradiol levels equivalent to those found during pregnancy have divergent effects on female immunity against influenza, highlighting the importance of vaccination during pregnancy to prevent severe influenza infections.
New peril on our roads: a retrospective study of electric scooter-related injuries.

INTRODUCTION The electric scooter has been gaining popularity locally as a commute mode. We aimed to understand the current landscape of electric scooter-related injuries in Singapore. METHODS A retrospective review was performed of the medical records of patients seen from 2015 to 2016 at an emergency department (ED) in Singapore. Patient demographics, circumstances of the accident, injuries sustained and clinical progress were analysed. RESULTS There were 36 cases, all of whom were electric scooter users. The median age was 34 (range 17-70) years and 66.7% were male. There was a 2.3-fold increase in the number of cases from 2015 to 2016. In 11 (30.6%) of cases, another road user was implicated. Two cases involved the use of protective equipment. 14 (38.9%) cases were conveyed by Emergency Medical Services. In the ED, 4 (11.1%), 17 (47.2%) and 15 (41.7%) cases were triaged as P1 (emergent), P2 (urgent) and P3 (ambulatory), respectively. Investigations were performed in the ED for 31 (86.1%) cases. External injuries were most common (72.2%), followed by extremity injuries (33.3%) with median Abbreviated Injury Scale scores of 1 and 2, respectively. Overall, the median Injury Severity Score was 1. Nine patients were admitted to the hospital with three requiring surgery. The median length of stay was 2 (range 1-6) days. CONCLUSION The incidence of electric scooter-related injuries appears to be on the rise and may potentially incur significant morbidity and healthcare costs. Further efforts at safety education and enforcement should be made to prevent accidents and minimise the impact of these injuries.
Localized algorithms for redundant readers elimination in RFID networks

ABSTRACT Redundant readers elimination is one of the fundamental optimization research problems in RFID networks. The problem is NP-hard and can be solved approximately using best known centralised set cover algorithms. However, either distributed or localised solutions for this problem are much more realistic and useful in practice. Different distributed and a few local algorithms are known in the literature. We propose a set of cellular automaton based algorithms for the redundant readers elimination optimization problem that are strictly local. We compare the performance of our algorithms in terms of eliminating redundant readers, tag read/write operation with other local algorithms and establish that our algorithms give much better results. We also compare our algorithms with the best known centralised approximation algorithms and find very competitive results even though our algorithms are localised. Graphical Abstract Redundant readers in RFID systems.