Miracle-dz/UniFAR-FTUs huggingface dataset:
“Pushing the Limits”: Rethinking Motor and Cognitive Resources After a Highly Challenging Balance Training Program for Parkinson Disease

Background There is growing evidence for the positive effects of exercise training programs on balance control in Parkinson disease (PD). To be effective, balance training needs to be specific, progressive, and highly challenging. Little evidence exists, however, for how people with PD‐related balance impairments perceive highly challenging and progressive balance training programs with dual‐task components. Objective The purpose of this study was to explore and describe perceptions of a highly challenging balance training program among people with mild to moderate PD. Design This study was qualitative in nature. In‐depth interviews were conducted with 13 individuals with mild to moderate PD who had participated in a highly challenging balance training program. Interview transcripts were analyzed using qualitative content analysis, with an inductive approach. Results The analysis revealed 3 subthemes concerning participants’ perceptions of highly challenging and progressive balance training: (1) movement to counter the disease, (2) dual‐task training in contrast to everyday strategies, and (3) the struggle to maintain positive effects. The first subtheme reflects how physical activity was used as a short‐term and long‐term strategy for counteracting PD symptoms and their progression. The second subtheme incorporates the described experiences of being maximally challenged in a secure and supportive group environment, circumstances that stood in contrast to participants’ everyday lives. The third subtheme describes participants’ long‐term struggle to maintain program effects on cognitive and physical function in the face of disease progression. Interpretation of the underlying patterns of these subthemes resulted in one overarching theme: training at the limits of balance capacity causes a rethinking motor and cognitive resources. Limitations The findings of this study cannot be considered to reflect the beliefs of those with weaker or negative beliefs concerning physical activity or be transferred to those at more severe stages of the disease. Conclusions Findings from this study suggest that being pushed to the limits of balance capacity provoked people with mild to moderate PD to rethink their individual motor and cognitive resources, a process that was further enabled by the PD‐specific group setting.
Drinking water contamination from perfluoroalkyl substances (PFAS): an ecological mortality study in the Veneto Region, Italy

Background Perfluoroalkyl substances (PFAS), a heterogeneous group of highly stable man-made chemicals, have been widely used since 1960s and can be detected almost ubiquitously in all environmental matrices. In Italy, on January 2014, drinking water contamination in an area of the Veneto Region was detected mainly due to the drain of fluorinated chemicals by a manufacturing company operating since 1964. Methods The present ecological mortality study was aimed at comparing mortality for some causes of death selected on the basis of previous reported associations, during the period 1980-2013, in municipalities with PFAS contaminated and uncontaminated drinking water on the basis of the levels indicated by the Italian National Health Institute (ISS). Sex-specific number, standardized mortality rates and rate ratios (RR) for PFAS contaminated and uncontaminated areas were computed for each cause of death through the ENEA epidemiological database. Results In both sexes, statistically significant RRs were detected for all causes mortality, diabetes, cerebrovascular diseases, myocardial infarction and Alzheimer's disease. In females, RRs significantly higher than 1.0 were also observed for kidney and breast cancer, and Parkinson's disease. Increased risk, although not statistically significant, was observed for bladder cancer in both sexes, and for testicular cancer, pancreatic cancer and leukemia in males only. Conclusions Higher mortality levels for some causes of death, possibly associated with PFAS exposure, were detected in contaminated municipalities in comparison with uncontaminated ones with similar socioeconomic status and smoking habits. These results warrant further individual level analytic studies to delineate casual associations.
Delegated persist ordering

Systems featuring a load-store interface to persistent memory (PM) are expected soon, making in-memory persistent data structures feasible. Ensuring persistent data structure recoverability requires constraints on the order PM writes become persistent. But, current memory systems reorder writes, providing no such guarantees. To complement their upcoming 3D XPoint memory, Intel has announced new instructions to enable programmer control of data persistence. We describe the semantics implied by these instructions, an ordering model we call synchronous ordering. Synchronous ordering (SO) enforces order by stalling execution when PM write ordering is required, exposing PM write latency on the execution critical path. It incurs an average slowdown of 7.21x over volatile execution without ordering in PM-write-intensive benchmarks. SO tightly couples enforcing order and flushing writes to PM, but this tight coupling is unneeded in many recoverable software systems. Instead, we propose delegated ordering, wherein ordering requirements are communicated explicitly to the PM controller, fully decoupling PM write ordering from volatile execution and cache management. We demonstrate that delegated ordering can bring performance within 1.93x of volatile execution, improving over SO by 3.73x.
Optimizing Adaptive Checkpointing Schemes for Grid Workflow Systems

One of the major challenges in wide use of grid workflow systems is fault tolerance and avoidance. Checkpointing schemes provide a way of fault detection and recovery. In our research, we focus on performance optimization of checkpointing schemes for grid workflow systems. We propose a set of adaptive checkpointing schemes that dynamically adjust the checkpointing intervals online by using store-checkpoints (SCPs) and compare-checkpoints (CCPs). These schemes can efficiently utilize comparison and storage operations and significantly improve the performance. Further, these schemes can calculate the optimal numbers of checkpoints by which minimize the mean execution time. We also expand the schemes from single-task execution scenarios to multitask execution scenarios. Simulation results show these schemes outstandingly increase the likelihood of timely task completion when faults occur
Dose–response modeling in mental health using stein‐like estimators with instrumental variables

A mental health trial is analyzed using a dose–response model, in which the number of sessions attended by the patients is deemed indicative of the dose of psychotherapeutic treatment. Here, the parameter of interest is the difference in causal treatment effects between the subpopulations that take part in different numbers of therapy sessions. For this data set, interactions between random treatment allocation and prognostic baseline variables provide the requisite instrumental variables. While the corresponding two‐stage least squares (TSLS) estimator tends to have smaller bias than the ordinary least squares (OLS) estimator; the TSLS suffers from larger variance. It is therefore appealing to combine the desirable properties of the OLS and TSLS estimators. Such a trade‐off is achieved through an affine combination of these two estimators, using mean squared error as a criterion. This produces the semi‐parametric Stein‐like (SPSL) estimator as introduced by Judge and Mittelhammer (2004). The SPSL estimator is used in conjunction with multiple imputation with chained equations, to provide an estimator that can exploit all available information. Simulated data are also generated to illustrate the superiority of the SPSL estimator over its OLS and TSLS counterparts. A package entitled SteinIV implementing these methods has been made available through the R platform. © 2017 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.
Eosinophilic colitis

A 57-year-old man, diagnosed with colon cancer stage III in July/2010, underwent surgery and received adjuvant chemotherapy with FOLFOX 4 (5-fluorouracil; calcium folinate and oxaliplatin), which ended in March/2011 after 12-cycles. It was then decided to maintain periodical surveillance. About 1 year later, the patient developed several episodes of diarrhoea, mainly during the night, and presented persistent peripheral eosinophilia in the blood count (range 585–1300 eosinophils/µL). Colonoscopy was performed, with the histological result showing eosinophilic infiltration of the colon, compatible with eosinophilic colitis. The patient was treated with a short course of budesonide, achieving resolution of symptoms, and has remained asymptomatic.
Concurrent Treatment with Prolonged Exposure for Co-Occurring Full or Subthreshold Posttraumatic Stress Disorder and Substance Use Disorders: A Randomized Clinical Trial

Background: To test whether an integrated prolonged exposure (PE) approach could address posttraumatic stress disorder (PTSD) symptoms effectively in individuals with co-occurring substance use disorders (SUD), we compared concurrent treatment of PTSD and SUD using PE (COPE) to relapse prevention therapy (RPT) for SUD and an active monitoring control group (AMCG). Methods: We conducted a randomized 12-week trial with participants (n = 110; 64% males; 59% African Americans) who met Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision criteria for full or subthreshold PTSD and SUD. Participants were randomly assigned to COPE (n = 39), RPT (n = 43), or AMCG (n = 28). Results: At the end-of-treatment, COPE and RPT demonstrated greater reduction in PTSD symptom severity relative to AMCG (COPE-AMCG = -34.06, p < 0.001; RPT-AMCG = -22.58, p = 0.002). Although the difference between COPE and RPT was not significant in the complete sample, the subset of participants with full (vs. subthreshold) PTSD demonstrated significantly greater reduction of PTSD severity in COPE relative to RPT. Both treatments were superior to AMCG in reducing the days of primary substance use (COPE-AMCG = -0.97, p = 0.01; RPT-AMCG = -2.07, p < 0.001). Relative to COPE, RPT showed significantly more improvement in SUD outcome at end-of-treatment (RPT-COPE = -1.10, p = 0.047). At 3-month follow-up, COPE and RPT maintained their treatment gains and were not significantly different in PTSD severity or days of primary substance use. Conclusion: COPE and RPT reduced PTSD and SUD severity in participants with PTSD + SUD. Findings suggest that among those with full PTSD, COPE improves PTSD symptoms more than a SUD-only treatment. The use of PE for PTSD was associated with significant decreases in PTSD symptoms without worsening of substance use.
Quality assurance concepts for adhesive bonding of composite aircraft structures – characterisation of adherent surfaces by extended NDT

In order to ensure the performance of adhesively joined load-critical composite structures, suitable technologies are needed to steadily monitor adherent surfaces prior to bonding and to detect adhesion properties of bonded components. A novel class of non-destructive testing (NDT) techniques, classified as extended non-destructive testing (ENDT), is required to ascertain selected physicochemical properties which are important for the performance of adhesive bonds in place of detecting material defects like conventional NDT methods do. The European FP7 project, ‘ENCOMB – Extended non-destructive testing of composite bonds’ aims in the identification, development, adaptation and validation of ENDT methods for characterisation of adherent surfaces and adhesive bond quality. Here, recent NDT techniques such as optically stimulated electron emission (OSEE) and aerosol wetting test (AWT) as well as laser-induced breakdown spectroscopy (LIBS) were advanced and applied in field, and without contacting carbon fibre-reinforced polymer (CFRP) surfaces for detecting different contamination layers such as release agent, moisture or hydraulic oil as well as thermal degradation of CFRP adherent surfaces before performing an adhesive bonding process. Sensitivity and accuracy of these techniques allow distinguishing surface states which are suitable for bonding of CFRP adherents from surface states which are unfavourable for bonding. ENDT using OSEE, AWT and LIBS facilitated the detection of layers of release agent as thin as one nanometre and thin layers resulting from hydraulic oil. OSEE investigations of adherent surfaces before adhesive bonding allowed the indication of all surface states of potential CFRP adherents, which according to previous studies, were related to application scenarios reducing the joint strength of resulting adhesive joints by 20–70%.
Impact of sleep deprivation on anaesthesia residents’ non-technical skills: a pilot simulation-based prospective randomized trial

Background Sleep deprivation is common in anaesthesia residents, but its impact on performance remains uncertain. Non-technical skills (team working, situation awareness, decision making, and task management) are key components of quality of care in anaesthesia, particularly in crisis situations occurring in the operating room. The impact of sleep deprivation on non-technical skills is unknown. We tested the hypothesis that in anaesthesia residents sleep deprivation is associated with impaired non-technical skills. Methods Twenty anaesthesia residents were randomly allocated to undergo a simulation session after a night shift [sleep-deprived (SLD) group, n =10] or after a night of rest [rested (R) group, n =10] from January to March 2015. The simulated scenario was a situation of crisis management in the operating room. The primary end point was a composite score of anaesthetists' non-technical skills (ANTS) assessed by two blinded evaluators. Results Non-technical skills were significantly impaired in the SLD group [ANTS score 12.2 (interquartile range 10.5-13)] compared with the R group [14.5 (14-15), P <0.02]. This difference was mainly accounted for by a difference in the team working item. On the day of simulation, the SLD group showed increased sleepiness and decreased confidence in anaesthesia skills. Conclusions In this randomized pilot trial, sleep deprivation was associated with impaired non-technical skills of anaesthesia residents in a simulated anaesthesia intraoperative crisis scenario. Trial registration NCT02622217.
Heart of glass anchors Rasip1 at endothelial cell-cell junctions to support vascular integrity

Heart of Glass (HEG1), a transmembrane receptor, and Rasip1, an endothelial-specific Rap1-binding protein, are both essential for cardiovascular development. Here we performed a proteomic screen for novel HEG1 interactors and report that HEG1 binds directly to Rasip1. Rasip1 localizes to forming endothelial cell (EC) cell-cell junctions and silencing HEG1 prevents this localization. Conversely, mitochondria-targeted HEG1 relocalizes Rasip1 to mitochondria in cells. The Rasip1-binding site in HEG1 contains a 9 residue sequence, deletion of which abrogates HEG1’s ability to recruit Rasip1. HEG1 binds to a central region of Rasip1 and deletion of this domain eliminates Rasip1’s ability to bind HEG1, to translocate to EC junctions, to inhibit ROCK activity, and to maintain EC junctional integrity. These studies establish that the binding of HEG1 to Rasip1 mediates Rap1-dependent recruitment of Rasip1 to and stabilization of EC cell-cell junctions. DOI: http://dx.doi. org/10.7554/eLife.11394. 001
A Randomized, Placebo-Controlled Study of High-Dose Baclofen in Alcohol-Dependent Patients—The ALPADIR Study

Aims Alcohol dependence is a major public health issue with a need for new pharmacological treatments. The ALPADIR study assessed the efficacy and safety of baclofen at the target dose of 180 mg/day for the maintenance of abstinence and the reduction in alcohol consumption in alcohol-dependent patients. Methods Three hundred and twenty adult patients (158 baclofen and 162 placebo) were randomized after alcohol detoxification. After a 7-week titration, the maintenance dose was provided for 17 weeks, then progressively decreased over 2 weeks before stopping. Results The percentage of abstinent patients during 20 consecutive weeks (primary endpoint) was low (baclofen: 11.9%; placebo: 10.5%) and not significantly different between groups (OR 1.20; 95%CI: 0.58 to 2.50; P = 0.618). A reduction in alcohol consumption was observed from month 1 in both groups, but the difference of 10.9 g/day at month 6 between groups, in favour of baclofen, was not statistically significant (P = 0.095). In a subgroup of patients with high drinking risk level at baseline, the reduction was greater with a difference at month 6 of 15.6 g/day between groups in favour of baclofen (P = 0.089). The craving assessed with Obsessive-Compulsive Drinking Scale significantly decreased in the baclofen group (P = 0.017). No major safety concern was observed. Conclusions This study did not demonstrate the superiority of baclofen in the maintenance of abstinence at the target dose of 180 mg/day. A tendency towards a reduction in alcohol consumption and a significantly decreased craving were observed in favour of baclofen. Short summary Baclofen was assessed versus placebo for maintenance of abstinence and reduction in alcohol consumption in alcohol-dependent patients. This study did not demonstrate the superiority of baclofen in the maintenance of abstinence. A tendency towards a reduction in alcohol consumption and a significantly decreased craving were observed in favour of baclofen.
Co-activation of STAT3 and YES-Associated Protein 1 (YAP1) Pathway in EGFR-Mutant NSCLC

Background: The efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in EGFR-mutant non–small cell lung cancer (NSCLC) is limited by adaptive activation of cell survival signals. We hypothesized that both signal transducer and activator of transcription 3 (STAT3) and Src-YES-associated protein 1 (YAP1) signaling are dually activated during EGFR TKI treatment to limit therapeutic response. Methods: We used MTT and clonogenic assays, immunoblotting, and quantitative polymerase chain reaction to evaluate the efficacy of EGFR TKI alone and in combination with STAT3 and Src inhibition in three EGFR-mutant NSCLC cell lines. The Chou-Talalay method was used for the quantitative determination of drug interaction. We examined tumor growth inhibition in one EGFR-mutant NSCLC xenograft model (n = 4 mice per group). STAT3 and YAP1 expression was evaluated in tumors from 119 EGFR-mutant NSCLC patients (64 in an initial cohort and 55 in a validation cohort) by quantitative polymerase chain reaction. Kaplan-Meier and Cox regression analyses were used to assess the correlation between survival and gene expression. All statistical tests were two-sided. Results: We discovered that lung cancer cells survive initial EGFR inhibitor treatment through activation of not only STAT3 but also Src-YAP1 signaling. Cotargeting EGFR, STAT3, and Src was synergistic in two EGFR-mutant NSCLC cell lines with a combination index of 0.59 (95% confidence interval [CI] = 0.54 to 0.63) for the PC-9 and 0.59 (95% CI = 0.54 to 0.63) for the H1975 cell line. High expression of STAT3 or YAP1 predicted worse progression-free survival (hazard ratio [HR] = 3.02, 95% CI = 1.54 to 5.93, P = .001, and HR = 2.57, 95% CI = 1.30 to 5.09, P = .007, respectively) in an initial cohort of 64 EGFR-mutant NSCLC patients treated with firstline EGFR TKIs. Similar results were observed in a validation cohort. Conclusions: Our study uncovers a coordinated signaling network centered on both STAT3 and Src-YAP signaling that limits targeted therapy response in lung cancer and identifies an unforeseen rational upfront polytherapy strategy to minimize residual disease and enhance clinical outcomes.
Seaweed-mediated indirect interaction between two species of meso-herbivores

Previous studies on trait-mediated trophic interactions in marine ecosystems were restricted to pair-wise interactions between one species of meso-herbivore and plant, though multi-grazer interactions are more common in nature. We investigated whether the feeding of one consumer, either the periwinkle Littorina littorea or the isopod Idotea baltica, affected consumption by the other consumer via anti-herbivory defence induction in the brown seaweed Fucus vesiculosus. To test the generality of our findings, we ran similar experiments with seaweed/grazer populations in the North and Baltic Seas (NE Atlantic). Grazer-specificity in induction strength was assessed by using the same species of grazer for induction and consumption. ‘Indirect’ induction effects were assessed by using different species of grazers for induction and consumption. Palatability assays were run with live algae and with reconstituted food to distinguish between different mechanisms of resistance. Grazing by herbivores induced a chemical defence in F. vesiculosus. In the North Sea population, the induced defences were only effective against I. baltica, regardless of inducer identity. The sensitive responses of I. baltica to the induced defences were also detected in the reconstituted food assays using Baltic Sea organisms. Thus, marine meso-grazers may be affected by previous feeding through the same or a different species of consumer by modified prey traits, such as induced chemical defences. Furthermore, the magnitude of the effect in the induced defences can be determined by species-specific sensitivity.
DEEPre: sequence-based enzyme EC number prediction by deep learning

Motivation Annotation of enzyme function has a broad range of applications, such as metagenomics, industrial biotechnology, and diagnosis of enzyme deficiency‐caused diseases. However, the time and resource required make it prohibitively expensive to experimentally determine the function of every enzyme. Therefore, computational enzyme function prediction has become increasingly important. In this paper, we develop such an approach, determining the enzyme function by predicting the Enzyme Commission number. Results We propose an end‐to‐end feature selection and classification model training approach, as well as an automatic and robust feature dimensionality uniformization method, DEEPre, in the field of enzyme function prediction. Instead of extracting manually crafted features from enzyme sequences, our model takes the raw sequence encoding as inputs, extracting convolutional and sequential features from the raw encoding based on the classification result to directly improve the prediction performance. The thorough cross‐fold validation experiments conducted on two large‐scale datasets show that DEEPre improves the prediction performance over the previous state‐of‐the‐art methods. In addition, our server outperforms five other servers in determining the main class of enzymes on a separate low‐homology dataset. Two case studies demonstrate DEEPre's ability to capture the functional difference of enzyme isoforms. Availability and implementation The server could be accessed freely at http://www.cbrc. kaust.edu. sa/DEEPre. Contact xin.gao@kaust.edu. sa Supplementary information Supplementary data are available at Bioinformatics online.