Miracle-dz/UniFAR-FTUs huggingface dataset:
Statistical Modeling and Aggregate-Weighted Scoring Systems in Prediction of Mortality and ICU Transfer: A Systematic Review

BACKGROUND The clinical deterioration of patientsin general hospital wards is an important safety issue. Aggregate-weighted early warning systems (EWSs) may not detect risk until patients present with acute decline. PURPOSE We aimed to compare the prognostic test accuracy and clinical workloads generated by EWSs using statistical modeling (multivariable regression or machine learning) versus aggregate-weighted tools. DATA SOURCES We searched PubMed and CINAHL using terms that described clinical deterioration and use of an advanced EWS. STUDY SELECTION The outcome was clinical deterioration (intensive care unit transfer or death) of adult patients on general hospital wards. We included studies published from January 1, 2012 to September 15, 2018. DATA EXTRACTION Following 2015 PRIMSA systematic review protocol guidelines; 2015 TRIPOD criteria for predictive model evaluation; and the Cochrane Collaboration guidelines, we reported model performance, adjusted positive predictive value (PPV), and conducted simulations of workup-to-detection ratios. DATA SYNTHESIS Of 285 articles, six studies reported the model performance of advanced EWSs, and five were of high quality. All EWSs using statistical modeling identified at-risk patients with greater precision than aggregate-weighted EWSs (mean AUC 0.80 vs 0.73). EWSs using statistical modeling generated 4.9 alerts to find one true positive case versus 7.1 alerts in aggregate-weighted EWSs; a nearly 50% relative workload increase for aggregate-weighted EWSs. CONCLUSIONS Compared with aggregate-weighted tools, EWSs using statistical modeling consistently demonstrated superior prognostic performance and generated less workload to identify and treat one true positive case. A standardized approach to reporting EWS model performance is needed, including outcome definitions, pretest probability, observed and adjusted PPV, and workup-to-detection ratio.
The role of peer victimization, sexual identity, and gender on unhealthy weight control behaviors in a representative sample of Texas youth.

OBJECTIVE The aim of the study is to examine the association between victimization and unhealthy weight control behaviors (UWCB), accounting for other key correlates of UWCB while considering the moderating role of sexual identity and gender. METHOD This study used data from the 2017 Texas Youth Risk Behavior Survey (YRBS), a representative sample of students in grades 9-12 in the U.S. state of Texas, including 2,067 students (1,754 heterosexuals and 313 sexual minorities). We used survey-weighted logistic regression to examine the association of sexual identity, gender, and victimization (dating violence, cyberbullying, and school bullying) with UWCB, after adjusting for demographic information and indicators of weight, physical activity, and support from adults. RESULTS Unhealthy weight control behaviors were associated with older age, being obese, lack of support from adults, low physical activity, and cyberbullying. A significant three-way interaction between gender, sexual identity and bullying showed that bullying was associated with high levels of UWCB among sexual minority males. DISCUSSION Our study highlights the role of victimization in health behaviors for stigmatized groups, and the importance of school efforts to implement an equitable and safe learning environment for all students.
Safety evaluation of 2′-deoxy-2′-fluoro nucleotides in GalNAc-siRNA conjugates

Abstract For oligonucleotide therapeutics, chemical modifications of the sugar-phosphate backbone are frequently used to confer drug-like properties. Because 2′-deoxy-2′-fluoro (2′-F) nucleotides are not known to occur naturally, their safety profile was assessed when used in revusiran and ALN-TTRSC02, two short interfering RNAs (siRNAs), of the same sequence but different chemical modification pattern and metabolic stability, conjugated to an N-acetylgalactosamine (GalNAc) ligand for targeted delivery to hepatocytes. Exposure to 2′-F-monomer metabolites was low and transient in rats and humans. In vitro, 2′-F-nucleoside 5′-triphosphates were neither inhibitors nor preferred substrates for human polymerases, and no obligate or non-obligate chain termination was observed. Modest effects on cell viability and mitochondrial DNA were observed in vitro in a subset of cell types at high concentrations of 2′-F-nucleosides, typically not attained in vivo. No apparent functional impact on mitochondria and no significant accumulation of 2′-F-monomers were observed after weekly administration of two GalNAc–siRNA conjugates in rats for ∼2 years. Taken together, the results support the conclusion that 2′-F nucleotides can be safely applied for the design of metabolically stabilized therapeutic GalNAc–siRNAs with favorable potency and prolonged duration of activity allowing for low dose and infrequent dosing.
Effects of Light Therapy on Mood and Insulin Sensitivity in Patients With Type 2 Diabetes and Depression: Results From a Randomized Placebo-Controlled Trial

OBJECTIVE Depression is common in patients with type 2 diabetes and adversely affects quality of life and diabetes outcomes. We assessed whether light therapy, an antidepressant, improves mood and insulin sensitivity in patients with depression and type 2 diabetes. RESEARCH DESIGN AND METHODS This randomized, double-blind, placebo-controlled trial included 83 patients with depression and type 2 diabetes. The intervention comprised 4 weeks of light therapy (10,000 lux) or placebo light therapy daily at home. Primary outcomes included depressive symptoms (Inventory of Depressive Symptomatology [IDS]) and insulin sensitivity (M-value derived from the results of a hyperinsulinemic-euglycemic clamp). Secondary outcomes were related psychological and glucometabolic measures. RESULTS Intention-to-treat analysis showed that light therapy was not superior to placebo in reducing depressive symptoms (−3.9 IDS points [95% CI −9.0 to 1.2]; P = 0.248) and had no effect on insulin sensitivity (0.15 mg/kg*min [95% CI −0.41 to 0.70]; P = 0.608). Analyses incorporating only those participants who accurately adhered to the light therapy protocol (n = 51) provided similar results, but did suggest positive effects of light therapy on depression response rates (≥50% reduction in IDS points) (26% more response; P = 0.031). Prespecified analysis showed effect moderation by baseline insulin sensitivity (P = 0.009) and use of glucose-lowering medication (P = 0.023). Light therapy did not affect depressive symptoms in participants with higher insulin sensitivity or those who use only oral glucose-lowering medication or none at all, but it did produce a relevant effect in participants with lower insulin sensitivity (−12.9 IDS points [95% CI −21.6 to −4.2]; P = 0.017) and a trend toward effectiveness in those using insulin (−12.2 IDS points [95% CI −21.3 to −3.1]; P = 0.094). Light therapy was well tolerated. CONCLUSIONS Although this trial is essentially inconclusive, secondary analyses indicate that light therapy might be a promising treatment for depression among a subgroup of highly insulin-resistant individuals with type 2 diabetes.
Cerebral Abnormalities in Adults with Ataxia-Telangiectasia

SUMMARY: Ataxia-telangiectasia, an autosomal recessive disorder caused by defect of the ataxia-telangiectasia mutated gene, is characterized by progressive neurologic impairment with cerebellar atrophy, ocular and cutaneous telangiectasia, immunodeficiency, heightened sensitivity to ionizing radiation and susceptibility to developing lymphoreticular malignancy. Supratentorial brain abnormalities have been reported only rarely. In this study, brain MRI was performed in 10 adults with ataxia-telangiectasia having stable neurologic impairment. Intracerebral telangiectasia with multiple punctate hemosiderin deposits were identified in 60% of subjects. These lesions were apparently asymptomatic. They are similar in appearance to radiation-induced telangiectasia and to cryptogenic vascular malformations. Also noted, in the 2 oldest subjects, was extensive white matter T2 hyperintensity, and in 1 of these a space-occupying fluid collection consistent with transudative capillary leak and edema as evidenced by reduced levels of metabolites on MR spectroscopic imaging. Asymptomatic supratentorial vascular abnormalities appear to be common in adults with ataxia-telangiectasia.
Automated classification of primary care patient safety incident report content and severity using supervised machine learning (ML) approaches

Learning from patient safety incident reports is a vital part of improving healthcare. However, the volume of reports and their largely free-text nature poses a major analytic challenge. The objective of this study was to test the capability of autonomous classifying of free text within patient safety incident reports to determine incident type and the severity of harm outcome. Primary care patient safety incident reports (n=31333) previously expert-categorised by clinicians (training data) were processed using J48, SVM and Naïve Bayes. The SVM classifier was the highest scoring classifier for incident type (AUROC, 0.891) and severity of harm (AUROC, 0.708). Incident reports containing deaths were most easily classified, correctly identifying 72.82% of reports. In conclusion, supervised ML can be used to classify patient safety incident report categories. The severity classifier, whilst not accurate enough to replace manual processing, could provide a valuable screening tool for this critical aspect of patient safety.
Puzzles and games: addressing different learning styles in teaching operating systems concepts

Because students have different learning styles, it's important to incorporate multiple teaching techniques into the classroom experience. One such technique is the use of puzzles and games in the classroom to reinforce the learning objectives. Many topics in Computer Science are well suited for coverage in such a game. Several in-class puzzles and games have been used in the Computer Science program at this institution in recent years. In basic and advanced courses, simple crossword puzzles reinforce terminology and Jeopardy! ®-style games help students master material with short answers. In the most recent iteration of the Operating Systems course, a BattleThreads game and a Process State Transition game helped students appreciate different approaches to process and thread management. The latter two games have been assessed for their effectiveness, providing several insights into what makes a good in-class game for teaching operating systems concepts, and how the existing games can be improved.
Foliar uptake of atmospheric nitrate by two dominant subalpine plants: insights from in situ triple-isotope analysis.

The significance of foliar uptake of nitrogen (N) compounds in natural conditions is not well understood, despite growing evidence of its importance to plant nutrition. In subalpine meadows, N-limitation fosters the dominance of specific subalpine plant species, which in turn ensures the provision of essential ecosystems services. Understanding how these plants absorb N and from which sources is important in predicting ecological consequences of increasing N deposition. Here, we investigate the sources of N to plants from subalpine meadows with distinct land-use history in the French Alps, using the triple isotopes (Δ17 O, δ18 O, and δ15 N) of plant tissue nitrate (NO3 - ). We use this approach to evaluate the significance of foliar uptake of atmospheric NO3 - (NO3 - atm ). The foliar uptake of NO3 - atm accounted for 4-16% of the leaf NO3 - content, and contributed more to the leaf NO3 - pool after peak biomass. Additionally, the gradual 15 N enrichment of NO3 - from the soil to the leaves reflected the contribution of NO3 - atm assimilation to plants' metabolism. The present study confirms that foliar uptake is a potentially important pathway for NO3 - atm into subalpine plants. This is of major significance as N emissions (and deposition) are predicted to increase globally in the future.
Evaluation of Linkage Disequilibrium, Effective Population Size and Haplotype Block Structure in Chinese Cattle

Simple Summary Evaluation of the population structure and linkage disequilibrium can offer important insights to fully understand the genetic diversity and population history of cattle, which can enable us to appropriately design and implement GWAS and GS in cattle. In this study, we characterized the extent of genome-wide LD and the haplotype block structure, and estimated the persistence of phase of Chinese indigenous cattle with Illumina BovineHD BeadChip. According to our study, 58K, 87K, 95K, 52K, and 52K markers would be necessary for SCHC, NCC, SWC, SIM, and WAG, respectively, in the implementation of GWAS and GS and combining a multipopulation with high persistence of phase is feasible for the implication of genomic selection for Chinese beef cattle. Abstract Understanding the linkage disequilibrium (LD) across the genome, haplotype structure, and persistence of phase between breeds can enable us to appropriately design and implement the genome-wide association (GWAS) and genomic selection (GS) in beef cattle. We estimated the extent of genome-wide LD, haplotype block structure, and the persistence of phase in 10 Chinese cattle population using high density BovinHD BeadChip. The overall LD measured by r2 between adjacent SNPs were 0.60, 0.67, 0.58, 0.73, and 0.71 for South Chinese cattle (SCHC), North Chinese cattle (NCC), Southwest Chinese cattle (SWC), Simmental (SIM), and Wagyu (WAG). The highest correlation (0.53) for persistence of phase across groups was observed for SCHC vs. SWC at distances of 0–50 kb, while the lowest correlation was 0.13 for SIM vs. SCHC at the same distances. In addition, the estimated current effective population sizes were 27, 14, 31, 34, and 43 for SCHC, NCC, SWC, SIM, and WAG, respectively. Our result showed that 58K, 87K, 95K, 52K, and 52K markers were required for implementation of GWAS and GS in SCHC, NCC, SWC, SIM, and WAG, respectively. Also, our findings suggested that the implication of genomic selection for multipopulation with high persistence of phase is feasible for Chinese cattle.
The central fibroblast growth factor receptor/beta klotho system: Comprehensive mapping in Mus musculus and comparisons to nonhuman primate and human samples using an automated in situ hybridization platform

Central activation of fibroblast growth factor (FGF) receptors regulates peripheral glucose homeostasis and reduces food intake in preclinical models of obesity and diabetes. The current work was undertaken to advance our understanding of the receptor expression, as sites of ligand action by FGF19, FGF21, and FGF1 in the mammalian brain remains unresolved. Recent advances in automated RNAscope in situ hybridization and droplet digital PCR (ddPCR) technology allowed us to interrogate central FGFR/beta klotho (Klb) system at the cellular level in the mouse, with relevant comparisons to nonhuman primate and human brain. FGFR1‐3 gene expression was broadly distributed throughout the CNS in Mus musculus, with FGFR1 exhibiting the greatest heterogeneity. FGFR4 expression localized only in the medial habenula and subcommissural organ of mice. Likewise, Klb mRNA was restricted to the suprachiasmatic nucleus (SCh) and select midbrain and hindbrain nuclei. ddPCR in the rodent hypothalamus confirmed that, although expression levels are indeed low for Klb, there is nonetheless a bonafide subpopulation of Klb+ cells in the hypothalamus. In NHP and human midbrain and hindbrain, Klb + cells are quite rare, as is expression of FGFR4. Collectively, these data provide the most robust central map of the FGFR/Klb system to date and highlight central regions that may be of critical importance to assess central ligand effects with pharmacological dosing, such as the putative interactions between the endocrine FGFs and FGFR1/Klb, or FGF19 with FGFR4.
HCV-Induced Epigenetic Changes Associated With Liver Cancer Risk Persist After Sustained Virologic Response

BACKGROUND & AIMS: Chronic hepatitis C virus (HCV) infection is an important risk factor for hepatocellular carcinoma (HCC). Despite effective antiviral therapies, the risk for HCC is decreased but not eliminated after a sustained virologic response (SVR) to direct-acting antiviral (DAA) agents, and the risk is higher in patients with advanced fibrosis. We investigated HCV-induced epigenetic alterations that might affect risk for HCC after DAA treatment in patients and mice with humanized livers. METHODS: We performed genome-wide ChIPmentation-based ChIP-Seq and RNA-seq analyses of liver tissues from 6 patients without HCV infection (controls), 18 patients with chronic HCV infection, 8 patients with chronic HCV infection cured by DAA treatment, 13 patients with chronic HCV infection cured by interferon therapy, 4 patients with chronic hepatitis B virus infection, and 7 patients with nonalcoholic steatohepatitis in Europe and Japan. HCV-induced epigenetic modifications were mapped by comparative analyses with modifications associated with other liver disease etiologies. uPA/SCID mice were engrafted with human hepatocytes to create mice with humanized livers and given injections of HCV-infected serum samples from patients; mice were given DAAs to eradicate the virus. Pathways associated with HCC risk were identified by integrative pathway analyses and validated in analyses of paired HCC tissues from 8 patients with an SVR to DAA treatment of HCV infection. RESULTS: We found chronic HCV infection to induce specific genome-wide changes in H3K27ac, which correlated with changes in expression of mRNAs and proteins. These changes persisted after an SVR to DAAs or interferon-based therapies. Integrative pathway analyses of liver tissues from patients and mice with humanized livers demonstrated that HCV-induced epigenetic alterations were associated with liver cancer risk. Computational analyses associated increased expression of SPHK1 with HCC risk. We validated these findings in an independent cohort of patients with HCV-related cirrhosis (n = 216), a subset of which (n = 21) achieved viral clearance. CONCLUSIONS: In an analysis of liver tissues from patients with and without an SVR to DAA therapy, we identified epigenetic and gene expression alterations associated with risk for HCC. These alterations might be targeted to prevent liver cancer in patients treated for HCV infection.
Hypothermic neuroprotection during reperfusion following exposure to aglycemia in central white matter is mediated by acidification

Hypoglycemia is a common iatrogenic consequence of type 1 diabetes therapy that can lead to central nervous system injury and even death if untreated. In the absence of clinically effective neuroprotective drugs we sought to quantify the putative neuroprotective effects of imposing hypothermia during the reperfusion phase following aglycemic exposure to central white matter. Mouse optic nerves (MONs), central white matter tracts, were superfused with oxygenated artificial cerebrospinal fluid (aCSF) containing 10 mmol/L glucose at 37°C. The supramaximal compound action potential (CAP) was evoked and axon conduction was assessed as the CAP area. Extracellular lactate was measured using an enzyme biosensor. Exposure to aglycemia, simulated by omitting glucose from the aCSF, resulted in axon injury, quantified by electrophysiological recordings, electron microscopic analysis confirming axon damage, the extent of which was determined by the duration of aglycemia exposure. Hypothermia attenuated injury. Exposing MONs to hypothermia during reperfusion resulted in improved CAP recovery compared with control recovery measured at 37°C, an effect attenuated in alkaline aCSF. Hypothermia decreases pH implying that the hypothermic neuroprotection derives from interstitial acidification. These results have important clinical implications demonstrating that hypothermic intervention during reperfusion can improve recovery in central white matter following aglycemia.
Validating Accelerometry as a Measure of Arm Movement for Children With Hemiplegic Cerebral Palsy.

BACKGROUND For children with hemiplegic cerebral palsy (HCP), rehabilitation aims to increase movement of the affected arm. However, no validated measure objectively examines this construct in pediatric practice or daily life. OBJECTIVE The objective of this study was to evaluate the criterion and known-groups validity of accelerometry as a measure of arm movement in children and adolescents with HCP. DESIGN This was a prospective cross-sectional study. METHODS Twenty-seven children and adolescents with typical development (3.4-13.9 years old) and 11 children and adolescents with HCP (4.7-14.7 years old; Manual Ability Classification System rating I or II) wore accelerometers on their wrists while engaged in 20 minutes of play, which included intermittent intervals of stillness and vigorous movement of the arms. Vector magnitude (VM) values identified the presence (VM > 2.0 counts per epoch) and absence (VM ≤ 2.0 counts per epoch) of arm movement for every 2-second epoch. Video was simultaneously recorded; each 2-second interval of footage was scored as "movement" or "no movement" for each arm. RESULTS Agreement between accelerometry and video observation was greater than or equal to 81%, and the prevalence-adjusted and bias-adjusted κ value was greater than or equal to 0.69 for both groups of participants; these results supported the criterion validity of accelerometry. The ratio of nondominant arm movement to dominant arm movement measured by accelerometry was significantly greater in participants with typical development (mean [SD] = 0.87 [0.09]) than in participants with HCP (mean = 0.78 [0.07]) on the basis of 10 age- and sex-matched pairs; these results supported known-groups validity. LIMITATIONS The small sample size of the group with HCP prevented the stratification of data by age. Participants with HCP had high or moderately high function of the affected arm; hence, the findings do not apply to children and adolescents with more significant hemiparesis. CONCLUSIONS Accelerometry is a valid measure of arm movement in children with HCP and children without HCP. These findings contribute to the development of innovative upper limb assessments for children with hemiparesis.
Feasibility of support vector machine learning in age‐related macular degeneration using small sample yielding sparse optical coherence tomography data

A retrospective pilot study is conducted to demonstrate the utility of a novel support vector machine learning (SVML) algorithm in a small three‐dimensional (3D) sample yielding sparse optical coherence tomography (spOCT) data for the automatic monitoring of neovascular (wet) age‐related macular degeneration (wAMD).