Miracle-dz/UniFAR-FTUs huggingface dataset:
Sources of variability and accuracy of performance assessment in the clinical pharmacology quality assurance (CPQA) proficiency testing program for antiretrovirals.

BACKGROUND The Clinical Pharmacology Quality Assurance (CPQA) program provides semi-annual proficiency testing of antiretroviral analytes for eleven U.S. and international clinical pharmacology laboratories to ensure inter-laboratory comparability. In this manuscript, we provide estimates of the main sources of variability and assess the accuracy of the algorithm for the assessment of performance. METHODS Descriptive statistics are reported from thirteen proficiency testing rounds from 2010-2016. Eight of the most common antiretroviral analytes were examined. Variance components analysis was employed to rank the relative contributions of clinical pharmacology laboratories, antiretroviral analyte and concentration category (low, medium and high) to bias and variability using mixed models. Binary classification metrics of the proficiency testing assessment algorithm are calculated in comparison to a model employing 95% prediction limits around estimated regression equations. RESULTS Clinical pharmacology laboratories provided 4,109 reported concentrations of 65 unique samples for each of the eight antiretroviral analytes across 13 proficiency testing rounds. Individual clinical pharmacology laboratory accounted for the greatest amount of total variability (4.4%). Individual clinical pharmacology laboratory and analyte combination (interaction) accounted for the greatest amount of bias (8.1%). Analyte alone accounted for 0.5% or less for total variability and bias. Overall, employing a ±20% acceptance window around the final target, 97% of individual reported concentrations were scored acceptable and 96% of antiretroviral /Round Scores were deemed satisfactory. Comparison with the regression model gave 100% sensitivity but only 34.47% specificity. Narrowing the acceptance window to ±15% improved specificity to 84.47% while maintaining a 99.17% sensitivity. CONCLUSION The current CPQA proficiency testing scoring algorithm which employ a ± 20% acceptance window appears to suffer from a low specificity and may be too lenient. A stricter ±15% acceptance window would increase specificity and overall accuracy while lowering the overall pass rate by only 3%.
White matter NAA/Cho and Cho/Cr ratios at MR spectroscopy are predictive of motor outcome in preterm infants.

PURPOSE To determine (a) whether diffuse white matter injury of prematurity is associated with an increased choline (Cho)-to-creatine (Cr) ratio and a reduced N-acetylaspartate (NAA)-to-Cho ratio and whether these measures can be used as biomarkers of outcome and (b) if changes in peak area metabolite ratios at magnetic resonance (MR) spectroscopy are associated with changes in T2 and fractional anisotropy (FA) at MR imaging. MATERIALS AND METHODS The local ethics committee approved this study, and informed parental consent was obtained for each infant. At term-equivalent age, 43 infants born at less than 32 weeks gestation underwent conventional and quantitative diffusion-tensor and T2-weighted MR imaging. Single-voxel point-resolved proton (hydrogen 1) MR spectroscopy was performed from a 2-cm(3) voxel centered in the posterior periventricular white matter. Outcome was evaluated by using Bayley scales at a corrected age of 1 year. Associations were investigated with Pearson product moment or Spearman rank order correlation. Differences in ratios in infants with and infants without impairment were tested by using t tests. RESULTS NAA/Cho and Cho/Cr ratios correlated with the scaled gross motor score and the composite motor score, independent of gestational age (P < .05). FA at diffusion-tensor MR imaging and T2 at MR imaging correlated with the NAA/Cho ratio (P < .05 for both) but not with the Cho/Cr ratio. Infants with motor scores of less than 85 (impaired) had an increased Cho/Cr ratio (P < .03) and a reduced NAA/Cho ratio (P < .01) compared to those without impairment. A combination of increased Cho/Cr ratio and decreased NAA/Cho ratio predicted impaired motor outcome at a corrected age of 1 year with a sensitivity of 0.80 (95% confidence interval [CI]: 0.57, 0.94) and a specificity of 0.80 (95% CI: 0.66, 0.88). CONCLUSION The combination of Cho/Cr and NAA/Cho ratios measured in the posterior periventricular white matter at term-equivalent age is predictive of motor outcome at 1 year in infants born at less than 32 weeks gestation.
Complete mitochondrial genome of maritime striped squirrel Tamiops maritimus (Rodentia: Sciuridae)

Abstract The complete mitochondrial genome of the maritime striped squirrel (Tamiops maritimus) was first sequenced and characterized. The genome was 16 523 bp in length, and the composition and the arrangement of genes were analogous to other rodents. The sequence of T. maritimus was used to construct phylogenetic tree with additional mitochondrial genomes of seven sciurid species available on GenBank. Phylogenetic result indicated that T. maritimus has a close relationship with T. swinhoei. Our mitochondrial genome data may provide information for species identification, diversity evaluation, and other studies about this genus.
Short‐term starvation stress at young adult stages enhances meiotic activity of germ cells to maintain spermatogenesis in aged male Caenorhabditis elegans

To survive and reproduce, living organisms must evolve numerous mechanisms to re‐adjust their physiology when encountering adverse conditions that subject them to severe stress. We found that short‐term starvation (STS) stress in young adult male Caenorhabditis elegans can significantly improve their vitality (relative to nonstressed males) when they are aged. In addition, we found that stress‐treated aged males maintained reproductive activity equivalent to young males, whereas nonstressed aged males quickly lost reproductive ability. STS stress can preserve sperm number and quality in aged male worms. Spermatogenesis involves germ cell mitosis and meiosis. We found that germ cell meiotic activity is more sensitive to aging than mitotic activity and is declining rapidly with age. We examined the role of numerous factors important for spermatogenesis on STS‐preserved spermatogenesis during aging. Our results show that mutant strains deficient in anaphase‐promoting complex/cyclosome (APC/C) function fail to exhibit the STS stress‐enhanced spermatogenesis found in wild‐type N2 worms, suggesting that the mechanism underlying starvation‐induced spermatogenesis involves the APC/C complex, a conserved ubiquitin‐protein ligase E3 complex. Furthermore, transgenic expression of FZY‐1/CDC‐20, a coactivator of APC/C, ameliorated the age‐associated decline of meiosis, similar to the hormetic effect of STS.
Generalized Extraction and Classification of Span-Level Clinical Phrases

Much of the critical information in a patient's electronic health record (EHR) is hidden in unstructured text. As such, there is an increasing role for automated text extraction and summarization to make this information available in a way that can be quickly and easily understood. While many clinical note text extraction techniques have been examined, most existing techniques are either narrowly targeted or focus primarily on concept-level extraction, potentially missing important contextual information. In contrast, in this work we examine the extraction of several clinical categories at the phrase level, attempting to provide the necessary context while still keeping the extracted elements concise. To do so, we employ a three-stage pipeline which extracts categorized phrases of interest using clinical concepts as anchor points. Results suggest the proposed method achieves performance comparable to that of individual human annotators.
Small Vessels-Big Problems : Novel Insights into Microvascular Mechanisms of Diseases Pericapillary basement membrane thickening in human skeletal muscles

Baum O, Bigler M. Pericapillary basement membrane thickening in human skeletal muscles. Am J Physiol Heart Circ Physiol 311: H654–H666, 2016. First published July 1, 2016; doi:10.1152/ajpheart.00048. 2016. —The basement membrane (BM) surrounding capillaries in skeletal muscles varies physiologically in thickness according to age, physical fitness, and anatomical site in humans. Furthermore, the pericapillary BM thickness (CBMT) increases pathophysiologically during several common disease states, including peripheral arterial disease and diabetes mellitus. This review on CBM thickening in human skeletal muscles is two pronged. First, it addresses the advantages/disadvantages of gridand tablet-based measuring and morphometric techniques that are implemented to assess the CBMT on transmission electron micrographs. Second, it deals with the biology of CBM thickening in skeletal muscles, particularly its possible causes, molecular mechanisms, and functional impact. CBM thickening is triggered by several physical factors, including diabetes-associated glycation, hydrostatic pressure, and inflammation. Increased biosynthesis of type IV collagen expression or repetitive cycles in pericyte or endothelial cell degeneration/proliferation appear to be most critical for CBM accumulation. A thickened CBM obviously poses a greater barrier for diffusion, lowers the microvascular elasticity, and impedes transcytosis of inflammatory cells. Our own morphometric data reveal the CBM enlargement to be not accompanied by the pericyte coverage. Owing to an overlap or redundancy in the capillary supply, CBM thickening in skeletal muscles might not be such a devastating occurrence as in organs with endarterial circulation (e.g., kidney and retina). CBM growth in skeletal muscles can be reversed by training or administration of antidiabetic drugs. In conclusion, CBM thickening in skeletal muscles is a microvascular remodeling process by which metabolic, hemodynamic, and inflammatory forces are integrated together and which could play a hitherto underestimated role in etiology/progression of human diseases.
Improved Time in Range and Glycemic Variability With Sotagliflozin in Combination With Insulin in Adults With Type 1 Diabetes: A Pooled Analysis of 24-Week Continuous Glucose Monitoring Data From the inTandem Program

OBJECTIVE To evaluate effects of the dual sodium–glucose cotransporter (SGLT) 1 and SGLT2 inhibitor sotagliflozin in combination with insulin on glucose time in range (TIR) and glucose excursions, postprandial glucose (PPG), and other glycemic metrics in adults with type 1 diabetes using masked continuous glucose monitoring (CGM). RESEARCH DESIGN AND METHODS Data sets from the inTandem1 (clinical trial reg. no. NCT02384941) and inTandem2 (clinical trial reg. no. NCT02421510) double-blind randomized trials evaluating sotagliflozin versus placebo in adults with type 1 diabetes treated with optimized insulin were pooled for analyses of masked CGM data from a subset of participants in each trial. The pooled cohort included patients randomized to receive placebo (n = 93), sotagliflozin 200 mg (n = 89), or sotagliflozin 400 mg (n = 96). The primary outcome was change from baseline to week 24 in glucose TIR (3.9–10.0 mmol/L [70–180 mg/dL]). Secondary end points included time below and above the target range and 2-h PPG level assessed after a standardized mixed meal. RESULTS Mean percentage of glucose TIR/percentage time spent at <3.9 mmol/L (<70 mg/dL) during week 24 was 51.6%/5.9%, 57.8%/5.5%, and 64.2%/5.5% with placebo, sotagliflozin 200 mg, and sotagliflozin 400 mg, respectively, which corresponded to a placebo-adjusted change from a baseline of +5.4%/−0.3% (P = 0.026; +1.3/−0.1 h/day) for sotagliflozin 200 mg and +11.7%/−0.1% (P < 0.001; +2.8/−0.02 h/day) for sotagliflozin 400 mg. Placebo-adjusted PPG reductions were 1.9 ± 0.7 mmol/L (35 ± 13 mg/dL; P = 0.004) and 2.8 ± 0.7 mmol/L (50 ± 13 mg/dL; P < 0.001) with sotagliflozin 200 and 400 mg, respectively. CONCLUSIONS Combined with optimized insulin in type 1 diabetes, sotagliflozin significantly increased glucose TIR without increasing time spent at <3.9 mmol/L and reduced PPG, thereby improving glycemic control.
The Role of Motivation as a Factor in Mental Fatigue

Objective: The aim of this study was to assess motivation as a factor in mental fatigue using subjective, performance, and physiological measures. Background: Sustained performance on a mentally demanding task can decrease over time. This decrement has two possible causes: a decline in available resources, meaning that performance cannot be sustained, and decrement in motivation, meaning a decline in willingness to sustain performance. However, so far, few experimental paradigms have effectively and continuously manipulated motivation, which is essential to understand its effect on mental fatigue. Method: Twenty participants performed a working memory task with 14 blocks, which alternated between reward and nonreward for 2.5 hr. In the reward blocks, monetary rewards could be gained for good performance. Besides reaction time and accuracy, we used physiological measures (heart rate variability, pupil diameter, eyeblink, eye movements with a video distractor) and subjective measures of fatigue and mental effort. Results: Participants reported becoming fatigued over time and invested more mental effort in the reward blocks. Even though they reported fatigue, their accuracy in the reward blocks remained constant but declined in the nonreward blocks. Furthermore, in the nonreward blocks, participants became more distractable, invested less cognitive effort, blinked more often, and made fewer saccades. These results showed an effect of motivation on mental fatigue. Conclusion: The evidence suggests that motivation is an important factor in explaining the effects of mental fatigue.
Molecular Epidemiology of Human Astrovirus in Stool Samples From Patients With Acute Gastroenteritis in Korea, 2013–2017

Background Human astroviruses (HAstVs) are one of the major causes of acute gastroenteritis. Classic HAstVs can be classified into eight genotypes. We investigated the positive rate of HAstVs and the distribution of HAstV genotypes in strains isolated from patients with acute gastroenteritis in Hwaseong, Korea, in 2013–2017. Methods Between November 2013 and December 2017, 3,519 stool samples were collected from patients with symptoms of acute gastroenteritis and tested for HAstV using multiplex PCR. For HAstV-positive samples, the ORF2 gene, which encodes a capsid protein, was genotyped by reverse-transcription PCR and sequencing. Phylogenetic analysis was performed to determine whether the sequences of the HAstVs differed by year. Results The positive rate of HAstV was 1.9% (67 samples). HAstV Type 1 was the most prevalent genotype (82.4%), and Types 4, 5, and 8 were also detected. Infection occurred year-round, with no distinct seasonal variation. Infection occurred at nearly all ages (55 days–81 years; median: 3 years), and the positive rate was substantially higher in children younger than five years. Phylogenetic analysis revealed three distinct clades of HAstV Type 1 according to the collection time. Conclusions Our results provide recent epidemiological data on HAstVs in Korea between 2013 and 2017. The finding of three distinct clades of HAstV Type 1 according to collection time suggests genetic evolution of HAstVs. These findings can enhance our knowledge on HAstV infection and viral evolution.
Enhanced and Tunable Electrorheological Capability using Surface Initiated Atom Transfer Radical Polymerization Modification with Simultaneous Reduction of the Graphene Oxide by Silyl-Based Polymer Grafting

In this study, a verified process of the “grafting from” approach using surface initiated atom transfer radical polymerization was applied for the modification of a graphene oxide (GO) surface. This approach provides simultaneous grafting of poly(2-(trimethylsilyloxy)ethyl methacrylate) (PHEMATMS) chains and a controllable reduction of the GO surface. This allows the fine tuning of its electrical conductivity, which is a crucial parameter for applications of such hybrid composite particles in electrorheological (ER) suspensions. The successful coating was confirmed by transmission electron microscopy and Fourier-transform infrared spectroscopy. The molecular characteristics of PHEMATMS were characterized by gel permeation chromatography. ER performance was elucidated using a rotational rheometer under various electric field strengths and a dielectric spectroscopy to demonstrate the direct impact of both the relaxation time and dielectric relaxation strength on the ER effectivity. Enhanced compatibility between the silicone oil and polymer-modified GO particles was investigated using contact angle measurements and visual sedimentation stability determination. It was clearly proven that the modification of the GO surface improved the ER capability of the system due to the tunable conductivity during the surface-initiated atom transfer radical polymerization (SI-ATRP) process and the enhanced compatibility of the GO particles, modified by polymer containing silyl structures, with silicone oil. These unique ER properties of this system appear very promising for future applications in the design of ER suspensions.
Can Children Prioritize More Valuable Information in Working Memory? An Exploration Into the Effects of Motivation and Memory Load

Recent research found no evidence that children aged 7–10 years are able to direct their attention to more valuable information in working memory. The current experiments examined whether children demonstrate this ability when the reward system used to motivate participants is engaging and age-appropriate. This was explored across different memory loads (3- vs. 4-item arrays) and modes of presentation (sequential vs. simultaneous). Younger (7–8 years) and older children (9–10 years) were shown 3 or 4 colored shapes and asked to recall the color of one probed item following a brief delay. Items were either presented sequentially (Experiment 1) or simultaneously (Experiment 2). Children completed a differential probe value condition, in which the first shape (Experiment 1) or the top-left shape (Experiment 2) was worth more points than the other items, and an equal probe value condition, in which all shapes were equally valuable. Children were told they could use the points collected to play a specially designed game at the end of the session, and that they would be given a prize if they collected enough points. When items were presented sequentially, significant probe value effects emerged, with children showing higher accuracy for the first item when this serial position was more valuable. This effect was consistent across age group and memory load. When items were encountered simultaneously, both groups showed probe value effects in the higher (4-item) memory load condition. This indicates that children can prioritize more valuable information in working memory when sufficiently motivated to do so.
Association between cellphone use while driving legislation and self-reported behaviour among adult drivers in USA: a cross-sectional study

Objectives Cellphone use behaviours can vary demographically in the USA. This study examined whether legislation restricting cellphone use while driving was associated with lower self-reported hand-held cellphone conversations or texting behaviours among adult drivers of different ages (19–24, 25–39, 40–59,≥60 years), sex, race/ethnicity (white non-Hispanic, black non-Hispanic, Hispanic, Other) or rurality (urban, rural). Design Cross-sectional study. Setting USA. Participants Individuals ≥19 years of age who indicated they were a current driver and participated in the 2011–2014 Traffic Safety Culture Index Surveys (n=9706). Primary outcome The exposure was the presence of a hand-held calling or texting ban applicable to all drivers (ie, universal) at time of survey. Modified Poisson regression with robust SE was used to estimate the risk of engaging in these self-reported behaviours. Results In fully adjusted models, universal texting bans were not associated with lower texting behaviours (adjusted risk ratio [aRR]=0.92; 95% CI 0.84, 1.01). In stratified, fully adjusted models, men and those of other racial/ethnic origin were 13% and 33% less likely, respectively (aRR=0.87; 95% CI 0.77, 0.98; aRR=0.67; 95% CI 0.46, 0.97), to engage in texting behaviours if a universal texting ban was effective in their state. Conversely, universal hand-held calling bans were associated with lower self-reported hand-held cellphone conversations across every sub-group. In fully adjusted models, the presence of a hand-held calling ban was associated with 40% lower (aRR=0.60, 95% CI 0.54, 0.67) self-reported hand-held cellphone conversations while driving. Conclusions Universal hand-held calling bans were associated with lower self-reported cellphone conversations for adult drivers. More interventional work targeting adult drivers may be needed to reduce texting while driving.
Expectancy modulates pupil size both during endogenous orienting and during re‐orienting of spatial attention: A study with isoluminant stimuli

We have recently demonstrated that when endogenous orienting of spatial attention is guided by central directional cues that reliably predict the position of lateral targets. Pupil Dilation (PDil) is higher as compared with directional cues that do not predict target position. These findings were interpreted as reflecting different levels of Locus Coeruleus‐Noradrenergic activity during endogenous orienting. In contrast to this, we were not able to highlight reliable differences between PDil responses to infrequent invalid targets that are associated with predictive cues and frequent invalid targets that are associated with non‐predictive ones. These null findings might have been due to the spurious influence of transitory changes in luminance at the moment of target presentation or to the short time window used for the analysis of target‐related changes in PDil. Here, we re‐explored cue‐ and target‐related changes in PDil using cue and target stimuli that were kept isoluminant to their background and long lasting cue and target periods for data recording and analysis. We fully replicate our previous cue‐related results and, in addition, we demonstrate that infrequent invalid targets in the predictive experimental condition evoke larger PDil as compared with frequent ones. Analyses with Linear Mixed Models highlighted that both during the cue and target period, higher levels of PDil were associated with slower reaction times. These findings confirm that PDil is a reliable marker of the expectancy components of endogenous cue‐related and exogenous target‐related orienting of spatial attention.