Miracle-dz/UniFAR-FTUs huggingface dataset:
Managing reversal of direct oral anticoagulants in emergency situations

Summary Anticoagulation is the cornerstone of prevention and treatment of venous thromboembolism (VTE) and stroke prevention in patients with atrial fibrillation (AF). However, the mechanisms by which anticoagulants confer therapeutic benefit also increase the risk of bleeding. As such, reversal strategies are critical. Until recently, the direct oral anticoagulants (DOACs) dabigatran, rivaroxaban, apixaban, and edoxaban lacked a specific reversal agent. This report is based on findings from the Anticoagulation Education Task Force, which brought together patient groups and professionals representing different medical specialties with an interest in patient safety and expertise in AF, VTE, stroke, anticoagulation, and reversal agents, to discuss the current status of anticoagulation reversal and fundamental changes in management of bleeding associated with DOACs occasioned by the approval of idarucizumab, a specific reversal agent for dabigatran, as well as recent clinical data on specific reversal agents for factor Xa inhibitors. Recommendations are given for when there is a definite need for a reversal agent (e.g. in cases of life-threatening bleeding, bleeding into a closed space or organ, persistent bleeding despite local haemostatic measures, and need for urgent interventions and/or interventions that carry a high risk for bleeding), when reversal agents may be helpful, and when a reversal agent is generally not needed. Key stakeholders who require 24–7/around-the-clock access to these agents vary among hospitals; however, from a practical perspective the emergency department is recommended as an appropriate location for these agents. Clearly, the advent of new agents requires standardised protocols for treating bleeding on an institutional level.
The role of latitudinal, genetic and temperature variation in the induction of diapause of Papilio glaucus (Lepidoptera: Papilionidae)

A key adaptation in insects for dealing with variable environmental conditions is the ability to diapause. The tiger swallowtail butterflies, Papilio glaucus and P. canadensis are ideal species to explore the genetic causes and population genetic consequences of diapause because divergence in this trait is believed to be a salient factor in maintaining a hybrid zone between these species. Yet little is known about the factors that influence diapause induction in this system. Here we explored how spatial (latitudinal), environmental (temperature) and genetic (hybridization) factors affect diapause induction in this system. Specifically, a series of growth chamber experiments using wild caught individuals from across the eastern United States were performed to: (1) evaluate how critical photoperiod varies with latitude, (2) isolate the stage in which induction occurs, (3) test whether changes in temperature affected rates of diapause induction, and (4) explore how the incidence of diapause is affected in hybrid offspring. We find that induction occurs in the larval stage, is not sensitive to a relatively broad range of temperatures, appears to have a complex genetic basis (i.e., is not simply a dominant trait following a Mendelian inheritance pattern) and that the critical photoperiod increases by 0.4 h with each increasing degree in latitude. This work deepens our understanding of how spatial, environmental and genetic variation influences a key seasonal adaptation (diapause induction) in a well‐developed ecological model system and will make possible future studies that explore how climatic variation affects the population dynamics and genetics of this system.
Analysing predictors for future high-cost patients using German SHI data to identify starting points for prevention.

BACKGROUND Demographic change influences not only the terms of health care, but also its financing. Hence, prevention is becoming a more important key to facing upcoming challenges. Aim of this study was to identify predictors for future high-cost patients and derive implications for potential starting points for prevention. METHODS Claims data from a German statutory health insurance agency were used. High-cost patients were defined as the 10% most expensive persons to insure in 2011. The predictors stemmed from the previous year. Logistic regression with stepwise forward selection for 10 sex- and age-specific subgroups was performed. Model fit was assessed by Nagelkerke's R-squared value. RESULTS Model fit values indicated well-suited models that yielded better results among younger age-groups. Identified predictors can be summarized as different sets of variables that mostly pertain to diseases. Some are rather broad and include different disorders, like the set of mental/behavioural disorders including depression and schizophrenia; other sets of variables are more homogenous, such as metabolic diseases, with diabetes mellitus (DM) being the dominant member of every subgroup. CONCLUSION Because diabetes was a significant predictor for future high-cost patients in all analysed subgroups, it should be considered as a potential starting point for prevention. The disease is specific enough to allow for the implementation of effective prevention strategies, and it is possible to intervene, even in patients already affected by DM. Furthermore, the monetary savings potential is probably high because the long-term complications of DM are expensive to treat and affect a large part of the population.
High rates of obesity prevalence in adults living in Central Greece: Data from the ARGOS Study

OBJECTIVE: To investigate the prevalence of obesity in adults of a large region of Central Greece. DESIGN: The target group was adults aged 18 to 79 years who were residents of the region of Thessaly for at least one year. A sample of 852 individuals stratified for sex and age were included. Each subject underwent a thorough physical examination and body mass index (BMI) was calculated from body weight and height. Waist and hip circumferences as well as body fat content were additionally measured. RESULTS: Mean (SD) BMI for the total population was 27.5±5.5 and was significantly higher in males than in females (28.2±4.4 vs. 26.9±6.2, p<0.001). The overall prevalence of obesity was 26.6% distributed equally between men (27.8%) and women (25.6%), whereas prevalence of overweight was 39.4% with male predominance (50.8% vs. 29.3%, p<0.001). Morbid obesity (MO) was found in 3.5% with female predominance. The prevalence of central obesity, using waist circumference cut-off points (>102cm for men, >88cm for women), was comparable in males (40.4%) and females (35.3%). There was a positive association between obesity, central obesity, and age. The prevalence of overweight (19.5%) and obesity (9.4%) in the age-range of 18–29 years almost doubled in the next decade of age and attained the highest value, respectively, in the age-range of 50 to 59 (48.2%), and of 60 to 70 years group (38.9%). CONCLUSIONS: The rates of overweight and obesity in the population of Thessaly are relatively high with overweight being more prominent in males than in females, whereas MO was higher in females compared to males.
Independent and cooperative regulation of staphylopine biosynthesis and trafficking by Fur and Zur

Staphylococcus aureus expresses the Cnt system implicated in the active transport of trace metals by synthesizing (CntKLM) and exporting (CntE) staphylopine, a metallophore chelating metals and then taken up by an ABC‐transporter (CntABCDF). This machinery is encoded in the cntKLMABCDFE operon, preceded by a non‐coding region (PcntK) and containing an internal promoter region (PcntA). PcntK comprises a Fur box followed by a Zur box, a sRNA transcription start and a repeated region, while PcntA comprises a Fur box that overlaps a Zur box. We found that PcntK promoter activity is attenuated by the repeated sequence and strictly controlled by Fur or Zur binding to its respective target sequences. Interestingly, we discovered a cooperative regulation of the PcntA activity by both Fur and Zur binding to the Fur/Zur box, by identifying a tripartite complex with DNA. Repression of PcntA is less sensitive to metal concentration and therefore loosely repressed as compared to PcntK activity. Furthermore, the Cnt system is essential for the optimal import of zinc, thereby linking regulation and function of Cnt. Overall, our results highlight the need for fine and differential tuning of staphylopine biosynthesis and trafficking in order to efficiently respond to metal starvation and optimize metal recovery.
Pulmonary Vascular Morphology as an Imaging Biomarker in Chronic Thromboembolic Pulmonary Hypertension

Patients with chronic thromboembolic pulmonary hypertension (CTEPH) have morphologic changes to the pulmonary vasculature. These include pruning of the distal vessels, dilation of the proximal vessels, and increased vascular tortuosity. Advances in image processing and computer vision enable objective detection and quantification of these processes in clinically acquired computed tomographic (CT) scans. Three-dimensional reconstructions of the pulmonary vasculature were created from the CT angiograms of 18 patients with CTEPH diagnosed using imaging and hemodynamics as well as 15 control patients referred to our Dyspnea Clinic and found to have no evidence of pulmonary vascular disease. Compared to controls, CTEPH patients exhibited greater pruning of the distal vasculature (median density of small-vessel volume: 2.7 [interquartile range (IQR): 2.5–3.0] vs. 3.2 [3.0–3.8]; P = 0.008), greater dilation of proximal arteries (median fraction of blood in large arteries: 0.35 [IQR: 0.30–0.41] vs. 0.23 [0.21–0.31]; P = 0.0005), and increased tortuosity in the pulmonary arterial tree (median: 4.92% [IQR: 4.85%–5.21%] vs. 4.63% [4.39%–4.92%]; P = 0.004). CTEPH was not associated with dilation of proximal veins or increased tortuosity in the venous system. Distal pruning of the vasculature was correlated with the cardiac index (R = 0.51, P = 0.04). Quantitative models derived from CT scans can be used to measure changes in vascular morphology previously described subjectively in CTEPH. These measurements are also correlated with invasive metrics of pulmonary hemodynamics, suggesting that they may be used to assess disease severity. Further work in a larger cohort may enable the use of such measures as a biomarker for diagnostic, phenotyping, and prognostic purposes.
Association between COL11A1 (rs1337185) and ADAMTS5 (rs162509) gene polymorphisms and lumbar spine pathologies in Chinese Han population: an observational study

Objectives A previous study identified a significant association between several single nucleotide polymorphisms (SNPs) and lumbar disc degeneration (LDD) in Indians. To validate the association between these SNPs and specific lumbar spine pathologies, we performed a case–control study in Chinese Han population. Design An observational study. Setting University Hospital in Nanning, China. Participants This study included 428 patients with LDD and 400 normal controls. Outcome measures Patients with LDD were classified into four subgroups, including disc herniation only (subgroup 1), discopathies or/and osteochondrosis associated with disc herniation (subgroup 2), spinal stenosis or/and spondylolisthesis (subgroup 3) and degenerative scoliosis (subgroup 4). This study was conducted by examining two aspects: environmental factors and SNP genotyping. The environmental factors were evaluated with a questionnaire survey including questions about body mass index, smoking habits, the physical demands of their job and exposure to vibrations. Rs1337185, rs5275, rs5277, rs7575934, rs3213718 and rs162509 were genotyped using a PCR-based invader assay. Results The physical workload was significantly higher in patients with lumbar spine pathologies than in the normal controls (p=0.035). The genotype and allele frequencies of rs1337185 and rs162509 were significantly different between the patients with LDD and the normal controls. In rs1337185, a significant association was found between the C allele (risk allele) and the presence of disc herniation (OR=1.80; 95% CI 1.21 to 2.68; p=0.003, adjusted p=0.012) and the presence of spinal stenosis and spondylolisthesis (OR=1.92; 95% CI 1.29 to 2.89; p=0.001, adjusted p=0.004). In rs162509, the G allele represented 1.58-fold increased risk to suffer from disc herniation (OR=1.58; 95% CI 1.20 to 2.09; p=0.001, adjusted p=0.004). Conclusion The SNPs rs1337185 in COL11A1 and rs162509 in ADAMTS5 are associated with susceptibility to LDD. The C allele of rs1337185 is risky for patients who are affected by lumbar pathologies such as disc herniation, stenosis and spondylolisthesis. The G allele of rs16250 represents a risk factor for the development of disc herniation.
Sequential regulatory activity prediction across chromosomes with convolutional neural networks

Models for predicting phenotypic outcomes from genotypes have important applications to understanding genomic function and improving human health. Here, we develop a machine-learning system to predict cell type-specific epigenetic and transcriptional profiles in large mammalian genomes from DNA sequence alone. Using convolutional neural networks, this system identifies promoters and distal regulatory elements and synthesizes their content to make effective gene expression predictions. We show that model predictions for the influence of genomic variants on gene expression align well to causal variants underlying eQTLs in human populations and can be useful for generating mechanistic hypotheses to enable fine mapping of disease loci.
Transmission of Staphylococcus aureus from Humans to Green Monkeys in The Gambia as Revealed by Whole-Genome Sequencing

ABSTRACT Staphylococcus aureus is an important pathogen of humans and animals. We genome sequenced 90 S. aureus isolates from The Gambia: 46 isolates from invasive disease in humans, 13 human carriage isolates, and 31 monkey carriage isolates. We inferred multiple anthroponotic transmissions of S. aureus from humans to green monkeys (Chlorocebus sabaeus) in The Gambia over different time scales. We report a novel monkey-associated clade of S. aureus that emerged from a human-to-monkey switch estimated to have occurred 2,700 years ago. Adaptation of this lineage to the monkey host is accompanied by the loss of phage-carrying genes that are known to play an important role in human colonization. We also report recent anthroponotic transmission of the well-characterized human lineages sequence type 6 (ST6) and ST15 to monkeys, probably because of steadily increasing encroachment of humans into the monkeys' habitat. Although we have found no evidence of transmission of S. aureus from monkeys to humans, as the two species come into ever-closer contact, there might be an increased risk of additional interspecies exchanges of potential pathogens. IMPORTANCE The population structures of Staphylococcus aureus in humans and monkeys in sub-Saharan Africa have been previously described using multilocus sequence typing (MLST). However, these data lack the power to accurately infer details regarding the origin and maintenance of new adaptive lineages. Here, we describe the use of whole-genome sequencing to detect transmission of S. aureus between humans and nonhuman primates and to document the genetic changes accompanying host adaptation. We note that human-to-monkey switches tend to be more common than the reverse and that a novel monkey-associated clade is likely to have emerged from such a switch approximately 2,700 years ago. Moreover, analysis of the accessory genome provides important clues as to the genetic changes underpinning host adaptation and, in particular, shows that human-to-monkey switches tend to be associated with the loss of genes known to confer adaptation to the human host.
What if I Had No Smells?

What would have happened if I did not have any code smell? This is an interesting question that no previous study, to the best of our knowledge, has tried to answer. In this paper, we present a method for implementing a what-if scenario analysis estimating the number of defective files in the absence of smells. Our industrial case study shows that 20% of the total defective files were likely avoidable by avoiding smells. Such estimation needs to be used with the due care though as it is based on a hypothetical history (i.e., zero number of smells and same process and product change characteristics). Specifically, the number of defective files could even increase for some types of smells. In addition, we note that in some circumstances, accepting code with smells might still be a good option for a company.
Micro-computed tomography studies of biomaterials and bone

This thesis is presented in two parts; the first part is a study of the structure and properties of bioceramic scaffolds used for orthopaedic tissue engineering and how these factors may influence bone regeneration. The second part of this thesis is a study of the effects of bone microarchitecture on the mechanical properties of the human proximal femur. Strategies for orthopaedic tissue engineering involve the use of a porous ceramic or polymer scaffold to serve as a template for bone regeneration. However, the design and engineering of these scaffolds is ad hoc. The effect of porosity, pore size, shape, interconnectivity, transport and mechanical properties on bone ingrowth is not well understood and remains a significant challenge to successful bone regeneration. We use a 3D micro-CT imaging and analysis approach to generate measures of local and non local pore size, pore interconnectivity, transport and mechanical properties directly from images of explanted hydroxyapatite constructs from a sheep model. We develop a method to accurately phase separate pore, bone and scaffold phases using a three-phase segmentation algorithm. We also observe a strong correlation with bone ingrowth andmeasures of non local pore size which account for pore accessibility. This study demonstrates the utility of micro-CT and quantitative 3D analysis to analyse tissue engineered implants. Osteoporosis and bone fracture at the hip are increasingly common with an aging population. Current methods to diagnose and treat osteoporosis are ambiguous about the role of bone microstructure in bone fragility. A micro-CT and 3D imaging approach on 13 proximal femora is implemented. We derive corrections to the standard Hip Structural Analysis assumptions of square and circular cross section at the femoral neck. A finite element method (FEM) is used to estimate the full anisotropic elastic stiffness tensor and correlations are noted with age, and structural parameters (such as topology and porosity). The strength of hips has been inferred via modulus-porosity relationships undertaken on trabeculae from within the femoral head and neck. We show that the modulus-porosity relationships at the whole hip scale differ significantly (by 100-200%) from relationships derived on trabecular subsets. Therefore, empirical relationships of modulus-porosity for trabeculae do not match data at the whole hip scale; a different empirical scaling and better fit is derived. Decreases in Young’s and shear moduli were observed with age while
IS-ASGD: Accelerating Asynchronous SGD using Importance Sampling

Variance reduction (VR) techniques for convergence rate acceleration of stochastic gradient descent (SGD) algorithm have been developed with great efforts recently. VR's two variants, stochastic variance-reduced-gradient (SVRG-SGD) and importance sampling (IS-SGD) have achieved remarkable progresses. Meanwhile, asynchronous SGD (ASGD) is becoming more critical due to the ever-increasing scale of the optimization problems. The application of VR in ASGD to accelerate its convergence rate has therefore attracted much interest and SVRG-ASGDs were proposed. However, we found that SVRG suffers dissatisfying performance in accelerating ASGD when datasets are sparse and large-scale. In such case, SVRG-ASGD's iterative computation cost is magnitudes higher than plain ASGD which makes it very inefficient. On the other hand, IS achieves improved convergence rate with few extra computation cost and is invariant to the sparsity of datasets. These advantages make it very suitable for the acceleration of ASGD on large-scale sparse datasets. In this paper we propose a novel IS-combined ASGD for efficient convergence rate acceleration, namely, IS-ASGD. We theoretically prove the superior convergence bound of IS-ASGD. Experimental results also demonstrate our statements.
Diversification and convergence of aposematic phenotypes: truncated receptors and cellular arrangements mediate rapid evolution of coloration in harlequin poison frogs

Aposematic signals represent one of the classical systems to study evolution and, as such, they have received considerable empirical and theoretical investigation. Despite the extensive literature on aposematic coloration, much uncertainty remains about genetic changes responsible for the repeated evolution of similar signals in multiple lineages. Here, we study the diversification and convergence of coloration among lineages of aposematic harlequin poison frogs (Oophaga histrionica complex). Our results suggest that different background phenotypes, showing different color and/or luminance contrast, have evolved independently at least twice in this group. We suggest that cellular arrangements are behind the striking diversity of color and patterns in this group and propose that differences in dorsal background color may be related to either or both, the presence/absence of xanthophores and the dispersion of melanosomes. Our genetic analyses support a role for the melanocortin receptor MC1R in melanosome aggregation, and we show evidence that two different mutations (∆433 and C432A) are responsible for the darker phenotypes that may display a more detectable, easier to learn, aposematic signal.
A National Study of Survival Trends and Conditional Survival in Nasopharyngeal Carcinoma: Analysis of the National Population-Based Surveillance Epidemiology and End Results Registry

Purpose Conditional survival (CS) provides important information on survival for a period of time after diagnosis. Currently, information on CS patterns of patients with nasopharyngeal carcinoma (NPC) is lacking. We aimed to analyze survival rate over time and estimate CS for NPC patients using a national population-based registry. Materials and Methods Patients diagnosed with NPC between 1973 and 2007 with at least 5-year follow-up were identified from the Surveillance Epidemiology End Results registry. Traditional survival rates and crude CS estimateswere calculated using Kaplan-Meier analysis. Risk-adjusted survival curves were plotted from the proportional hazards model using the correct group prognosis method. Results registry. Traditional survival rates and crude CS estimateswere calculated using Kaplan-Meier analysis. Risk-adjusted survival curves were plotted from the proportional hazards model using the correct group prognosis method. Results For 7,713 patients analyzed, adjusted baseline 5-year overall survival improved significantly from 36.0% in patients diagnosed in 1973-1979, 41.7% in 1980-1989, 46.6% in 1990-1999, to 54.7% in 2000-2007 (p < 0.01). CS analysis demonstrated that for every additional year survived, adjusted probability of surviving the next 5 years increased from 66.7% (localized), 54.0% (regional), and 35.3% (distant) at the time of diagnosis, to 83.7% (localized), 75.0% (regional), and 62.2% (distant) for patients who had survived 5 years. Adjusted 5-year CS differed among age, sex, tumor histology, ethnicity, and stage subgroups initially, but converged with time. Conclusion Treatment outcomes of NPC patients have greatly improved over the decades. Increases in CS become more prominent in patients with distant disease than in those with localized or regional disease as patients survive longer. CS provides more dynamic prognostic information for patients who have survived a period of time after diagnosis.