Miracle-dz/UniFAR-FTUs huggingface dataset:
Optimal splitting for rare-event simulation

Simulation is a popular tool for analyzing large, complex, stochastic engineering systems. When estimating rare-event probabilities, efficiency is a big concern, since a huge number of simulation replications may be needed in order to obtain a reasonable estimate of the rare-event probability. The idea of splitting has emerged as a promising variance reduction technique. The basic idea is to create separate copies (splits) of the simulation whenever it gets close to the rare event. Some splitting methods use an equal number of splits at all levels. This can compromise the efficiency and can even increase the estimation variance. This article formulates the problem of determining the number of splits as an optimization problem that minimizes the variance of an estimator subject to a constraint on the total computing budget. An optimal solution for a certain class of problems is derived that is then extended to the problem of choosing the better of two designs, where each design is evaluated via rare-event simulation. Theoretical results for the improvements that are achievable using the methods are provided. Numerical experiments indicate that the proposed approaches are efficient and robust.
Profiling students via clustering in a flipped clinical skills course using learning analytics

Abstract Flipped classrooms have become popular as a student-centered approach in medical education because they allow students to improve higher-order thinking skills and problem-solving applications during in-class activities. However, students are expected to study videos and other class materials before class begins. Learning analytics and unsupervised machine learning algorithms (clustering) can be used to examine the pre-class activities of these students to identify inadequate student preparation before the in-class stage and make appropriate interventions. Furthermore, the students’ profiles, which provide their interaction strategies towards online materials, can be used to design appropriate interventions. This study investigates student profiles in a flipped classroom. The learning management system interactions of 375 medical students are collected and preprocessed. The k-means clustering algorithms examined in this study show a two-cluster structure: ‘high interaction’ and ‘low-interaction. ’ These results can be used to help identify low-engaged students and give appropriate feedback.
Electrophoretic mobilization in capillary isoelectric focusing by a weak acid or an acidic ampholyte as catholyte assessed by computer simulation

Capillary isoelectric focusing (CIEF) with cationic electrophoretic mobilization induced via replacing the catholyte with the anolyte or a solution of another acid or amino acid was investigated by computer simulation for a wide range pH gradient bracketed between two amphoteric spacers and short electrode vials with a higher id than the capillary. Dynamic simulations provide insight into the complexity of the mobilizing process in a hitherto inaccessible way. The electrophoretic mobilizing process begins with the penetration of the mobilizing compound through the entire capillary, is followed by a gradual or steplike decrease of pH, and ends in an environment with a non‐homogenous solution of the mobilizer. Analytes do not necessarily pass the point of detection in the order of decreasing pI values. Cationic mobilization encompasses an inherent zone dispersing and refocusing process toward the capillary end. This behavior is rather strong with phosphoric acid and citric acid, moderate with aspartic acid, glutamic acid (GLU), formic acid, and acetic acid and less pronounced in the absence of the cathodic spacer. The data reveal that optical detectors should not be placed before 90% of capillary length. Aspartic acid, GLU, formic acid, and acetic acid provide an environment with a continuously decreasing pH that explains their successful use in optimized two‐step CIEF protocols.
Chronic Sub-Clinical Systemic Metabolic Acidosis – A Review with Implications for Clinical Practice

When arterial serum pH remains near the lower pH limit of 7.35 for protracted periods of time, a low-grade, sub-clinical form of acidosis results, referred to in this review as chronic, sub-clinical, systemic metabolic acidosis (CSSMA). This narrative review explores the scientific basis for CSSMA, its consequences for health, and potential therapeutic interventions. The major etiology of CSSMA is the shift away from the ancestral, alkaline diet which was rich in fruit and vegetables, toward the contemporary, acidogenic ‘Westernized’ diet characterized by higher animal protein consumption and lack of base forming minerals. Urine pH is reduced with high dietary acid load and may be a convenient marker of CSSMA. Evidence suggests further that CSSMA negatively influences cortisol levels potentially contributing significantly to the pathophysiology thereof. Both CSSMA and high dietary acid load are associated with the risk and prognosis of various chronic diseases. Clinical trials show that CSSMA can be addressed successfully through alkalizing the diet by increasing fruit and vegetable intake and/or supplementing with alkaline minerals. This review confirms the existence of a significant body of evidence regarding this low-grade form of acidosis as well as evidence to support its diverse negative implications for health, and concludes that CSSMA is a condition warranting further research.
GC-globulin/vitamin D-binding Protein is Required for Pancreatic α Cell 2 Adaptation to Metabolic Stress.

GC-globulin (GC), or vitamin D-binding protein, is a multifunctional protein involved in transport of circulating vitamin 25(OH)D and fatty acids, as well as actin-scavenging. In the pancreatic islets, the gene encoding GC, GC, is highly-localized to glucagon-secreting α cells. Despite this, the role of GC in α cell function is poorly understood. We previously showed that GC is essential for α cell morphology, electrical activity and glucagon secretion. We now show that loss of GC exacerbates α cell failure during metabolic stress. High fat diet-fed GC-/- mice have basal hyperglucagonemia, which is associated with decreased α cell size, impaired glucagon secretion and Ca2+ fluxes, and changes in glucose-dependent F-actin remodelling. Impairments in glucagon secretion can be rescued using exogenous GC to replenish α cell GC levels, increase glucagon granule area and restore the F-actin cytoskeleton. Lastly, GC levels decrease in α cells of donors with type 2 diabetes, which is associated with changes in α cell mass, morphology and glucagon expression. Together, these data demonstrate an important role for GC in α cell adaptation to metabolic stress.
Validity of Visuoconstructional Assessment Methods within Healthy Elderly Greek Australians: Quantitative and Error Analysis.

AIMS Visuospatial skills are frequently assessed with drawing tests. Research has suggested that the use of drawing tasks in low educated groups may lack the ability to discriminate healthy individuals from clinical populations. The aims of this study were to investigate the validity of visuoconstructional tests in a sample of older Greek Australian immigrants and compare their performances to a matched sample of patients with Alzheimer's disease (ad). METHOD We assessed visuoconstructional performances in a sample of 90 healthy older Greek Australians, with a primary school level of education, and compared performances to a demographically matched sample of 20 Greek Australians with a diagnosis of ad on four visuoconstructional drawing tests: Greek cross, four-pointed star, intersecting pentagons, and the Necker Cube. RESULTS While healthy participants tended to outperform the ad group on most copy tasks, high fail rates within the healthy sample were observed for the intersecting pentagons and Necker cube (78% and 73% fail rates, respectively) when using established clinical cut-off scores. High rates of curved angle, omission, distorted relation between elements, spatial disorganization and three-dimensional design errors were found across the four-pointed star, intersecting pentagons, and the Necker cube in both healthy participants and those with ad. Exploratory receiver operating characteristic curve analysis revealed that, with perhaps the exception of the Greek cross, meaningful sensitivity and specificity could not be reached for the four-pointed star, intersecting pentagons, and Necker cube. CONCLUSION Cognitively healthy immigrants with low education appear to be at a disadvantage when completing visuoconstructional drawing tests, as their performance may be misinterpreted as indicating cognitive impairment. Future research is needed to identify alternative approaches to assess visuoconstructional ability in culturally and linguistically diverse older cohorts with limited education.
Pierre3D: a 3D stochastic rockfall simulator based on random ground roughness and hyperbolic restitution factors

The use of dynamic computational methods has become indispensable for addressing problems related to rockfall hazard. Although a number of models with various degrees of complexity are available, model parameters are rarely calibrated against observations from rockfall experiments. A major difficulty lies in reproducing the apparent randomness of the impact process related to both ground and block irregularities. Calibration of rigorous methods capable of explicitly modeling trajectories and impact physics of irregular blocks is difficult, as parameter spaces become too vast and the quality of model input and observation data are insufficient. The model presented here returns to the simple “lumped-mass” approach and simulates the characteristic randomness of rockfall impact as a stochastic process. Despite similarities to existing approaches, the model presented here incorporates several novel concepts: (i) ground roughness and particle roughness are represented as a random change of slope angle at impact.
Effects of green tea catechins and exercise training on body composition parameters

Abstract The impact of phytochemicals, as green tea catechins, on body composition measures has become a relevant topic as ongoing epidemiological evidence suggests their potential role in weight loss. Although catechins have been shown to modulate fat and energy metabolism, clinical effects of green tea consumption still remain controversial. Given the role played by physical exercise in weight management, it is important to determine whether the association of catechins and exercise is able to improve outcomes over and above the beneficial effects of exercise alone. Considering that scientific findings on this topic are not entirely consistent, aim of the present review was to assess the current scientific literature regarding the interplay between green tea catechins and exercise in overweight and obese populations. In particular, it was evaluated whether the addition of green tea supplementation to exercise training was able to further improve the exercise‐induced changes in body composition parameters.
Parental Risk and Protective Factors in Child Maltreatment: A Systematic Review of the Evidence

This study systematically reviews and synthesizes evidence on parental risk and protective factors along with identifying differences in the presence of these factors based on maltreatment type. In all, 68 quantitative, published, empirical studies were included from electronic databases for the systematic review. Quality appraisal did not exclude any studies and data were extracted from all. Results were narratively synthesized using the Risk and Resilience Ecological framework. The findings revealed more risk factors on the micro (individual and family) ecological level compared to mezzo and macro levels. At the micro level, findings mirror results of prior systematic reviews such as parental substance abuse, history of childhood maltreatment, and intimate partner violence (IPV). Social support was the most significant protective factor across all ecological levels and across all maltreatment types except child sexual abuse but differed in definition widely across studies. Physical abuse had the most risk factors unique to this type followed by neglect, and IPV was a common risk factor across all maltreatment types. Fewer studies on emotional abuse, sexual abuse, and protective factors were identified. The findings of this review delineated key parental risk and protective factors at various ecological levels along with associations between distinct factors and types of maltreatment. Interventions working with parents to reduce child maltreatment risk can use these findings to guide development of targeted programs for families based on risk and maltreatment type. For researchers, the findings can guide further investigation in under-researched areas of parental sexual and emotional abuse and protective factors.
Monitoring of 3C 66A during an extended outburst. I. The light curves

We present results from a two year intensive monitoring of BL Lac object 3C 66A (PKS 0219+428). This object was observed in outburst during these two years. It reached the brightest ever observed magnitude on V =13.59 (1.2.1995) and on K =10.59 (15.2.1994). The optical and infrared light curves are characterised by randomly distributed fast flares, lasting a few days and well defined outbursts lasting a week or two. On top of these flares we can occasionally see small amplitude microvariability. No clear correlation can be found between the spectral behaviour and the occurrence of these flares. In the radio bands 3C 66A was quite faint and very stable compared to the optical variations. The light curves will be presented with preliminary analysis and discussions on the possible causes for the observed variations.
Piezo1 channel‐mediated Ca2+ signaling inhibits lipopolysaccharide‐induced activation of the NF‐κB inflammatory signaling pathway and generation of TNF‐α and IL‐6 in microglial cells

Microglial cells are crucial in maintaining central nervous system (CNS) homeostasis and mediating CNS disease pathogenesis. Increasing evidence supports that alterations in the mechanical properties of CNS microenvironments influence glial cell phenotypes, but the mechanisms regulating microglial cell function remain elusive. Here, we examined the mechanosensitive Piezo1 channel in microglial cells, particularly, how Piezo1 channel activation regulates pro‐inflammatory activation and production of pro‐inflammatory cytokines, using BV2 and primary microglial cells. Piezo1 expression in microglial cells was detected both at mRNA and protein levels. Application of Piezo1 channel activator Yoda1 induced Ca2+ flux to increase intracellular Ca2+ concentration that was reduced by treatment with ruthenium red, a Piezo1 inhibitor, or Piezo1‐specific siRNA, supporting that Piezo1 functions as a cell surface Ca2+‐permeable channel. Priming with lipopolysaccharide (LPS) induced microglial cell activation and production of TNF‐α and IL‐6, which were inhibited by treatment with Yoda1. Furthermore, LPS priming induced the activation of ERK, p38 MAPKs, and NF‐κB. LPS‐induced activation of NF‐κB, but not ERK and p38, was inhibited by treatment with Yoda1. Yoda1‐induced inhibition was blunted by siRNA‐mediated depletion of Piezo1 expression and, furthermore, treatment with BAPTA‐AM to prevent intracellular Ca2+ increase. Collectively, our results support that Piezo1 channel activation downregulates the pro‐inflammatory function of microglial cells, especially production of TNF‐α and IL‐6, by initiating intracellular Ca2+ signaling to inhibit the NF‐κB inflammatory signaling pathway. These findings reveal Piezo1 channel activation as a previously unrecognized mechanism regulating microglial cell function, raising an interesting perspective on targeting this molecular mechanism to alleviate neuroinflammation and associated CNS pathologies.
Comparison of Clinical Outcomes and Complications Between Endoscopic and Minimally Invasive Transforaminal Lumbar Interbody Fusion for Lumbar Degenerative Diseases: A Systematic Review and Meta-analysis

Study design Systematic review and meta-analysis. Objective Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is a classic surgical procedure for the treatment of lumbar degenerative diseases (LDD). With the development of endoscopic technology, endoscopic transforaminal lumbar interbody fusion (Endo-TLIF) can also achieve adequate decompression and interbody fusion. However, whether Endo-TLIF is superior to MIS-TLIF has not been adequately studied. In this systematic review and meta-analysis, we aimed to evaluate the treatment difference between Endo-TLIF vs MIS-TLIF. Methods We conducted a systematic review and meta-analysis of the studies to compare the clinical outcomes and complications associated with Endo-TLIF vs. MIS-TLIF for the treatment of LDD. A literature search was conducted using the PubMed, Embase, Cochrane Library and Scopus databases for studies published up to April 1, 2022. Both retrospective and prospective studies that compared between Endo-TLIF and MIS-TLIF were included. Results A total of 8 studies involving 581 patients were finally included in this meta-analysis. Endo-TLIF significantly prolonged the operation time, but reduced the blood loss amount and length of hospital stay. Moreover, Endo-TLIF was superior to MIS-TLIF on relief of back pain and functional recovery in the early postoperative period. However, there were no significantly differences in long-term clinical outcomes, fusion rate and incidence of complications between Endo-TLIF and MIS-TLIF. Conclusions Endo-TLIF was similar to MIS-TLIF in the long-term clinical outcomes, fusion and complication rates. Endo-TLIF prolongs the operation time, but shortens the length of hospital stay, and has the advantages of less surgical trauma, less blood loss, faster recovery, and early postoperative back pain relief.
Workplace violence among nurses in a Penang hospital: Prevalence and risk factors.

INTRODUCTION Workplace violence (WPV) has become a universal concern and is perceived as a serious safety and health threat, especially in healthcare settings. Very few studies have been done previously to determine the prevalence of WPV and associated risk factors among nurses in Malaysia. Among the health professionals, nurses spend most of their time with patients compared to other healthcare professionals. Several studies suggested that nurses had a higher risk of experiencing WPV. This study determined the prevalence and associated risk factors of WPV among nurses in a government hospital. MATERIALS AND METHODS This cross-sectional study involved 410 randomly selected respondents among nurses in a government hospital in Penang, Malaysia. Data were gathered through a self-administered questionnaire consisting of a standardised questionnaire regarding WPV. RESULTS The prevalence of reported WPV was 43.9%. The most common forms of WPV were verbal abuse (82.2%), followed by psychological violence (8.9%), physical violence (8.3%), and sexual violence (0.6%). The perpetrators were primarily among relatives of patients (51.7%), followed by patients (30%). Multiple logistic regression demonstrated that nurses working in the emergency department (ED) were six times more likely to experience WPV than in other departments (adjusted odds ratio (AOR) 6.139, 95% CI: 1.28 - 4.03). In addition, nurses in the age group of ≤30 years old were twice more likely to experience WPV (AOR 2.275, 95% CI: 3.4-11.08). CONCLUSION This study indicates that the prevalence of WPV among nurses is high and most common among young nurses and those working in ED. Hence, hospital management should develop guidelines and comprehensive policies to prevent WPV. In addition, education and training, especially among young nurses and those working in the ED, are needed to increase their knowledge in the management and prevention of WPV and counselling sessions for nurses who have experienced WPV.
Long-term benefits of nonpharmaceutical interventions for endemic infections are shaped by respiratory pathogen dynamics

Significance Nonpharmaceutical interventions, such as mask wearing, introduced to limit the spread of COVID-19 have proved effective at reducing cases of other respiratory diseases. A key public health question is whether these interventions could be introduced long term to limit outbreaks of diseases such as influenza. Here, we use epidemic models to show that the effect of mask wearing on endemic disease is likely short lived. Over longer time horizons, outbreaks may return while interventions are in place, as population immunity decreases.
Image analysis workflows to reveal the spatial organization of cell nuclei and chromosomes

ABSTRACT Nucleus, chromatin, and chromosome organization studies heavily rely on fluorescence microscopy imaging to elucidate the distribution and abundance of structural and regulatory components. Three-dimensional (3D) image stacks are a source of quantitative data on signal intensity level and distribution and on the type and shape of distribution patterns in space. Their analysis can lead to novel insights that are otherwise missed in qualitative-only analyses. Quantitative image analysis requires specific software and workflows for image rendering, processing, segmentation, setting measurement points and reference frames and exporting target data before further numerical processing and plotting. These tasks often call for the development of customized computational scripts and require an expertise that is not broadly available to the community of experimental biologists. Yet, the increasing accessibility of high- and super-resolution imaging methods fuels the demand for user-friendly image analysis workflows. Here, we provide a compendium of strategies developed by participants of a training school from the COST action INDEPTH to analyze the spatial distribution of nuclear and chromosomal signals from 3D image stacks, acquired by diffraction-limited confocal microscopy and super-resolution microscopy methods (SIM and STED). While the examples make use of one specific commercial software package, the workflows can easily be adapted to concurrent commercial and open-source software. The aim is to encourage biologists lacking custom-script-based expertise to venture into quantitative image analysis and to better exploit the discovery potential of their images. Abbreviations: 3D FISH: three-dimensional fluorescence in situ hybridization; 3D: three-dimensional; ASY1: ASYNAPTIC 1; CC: chromocenters; CO: Crossover; DAPI: 4',6-diamidino-2-phenylindole; DMC1: DNA MEIOTIC RECOMBINASE 1; DSB: Double-Strand Break; FISH: fluorescence in situ hybridization; GFP: GREEN FLUORESCENT PROTEIN; HEI10: HUMAN ENHANCER OF INVASION 10; NCO: Non-Crossover; NE: Nuclear Envelope; Oligo-FISH: oligonucleotide fluorescence in situ hybridization; RNPII: RNA Polymerase II; SC: Synaptonemal Complex; SIM: structured illumination microscopy; ZMM (ZIP: MSH4: MSH5 and MER3 proteins); ZYP1: ZIPPER-LIKE PROTEIN 1.