Miracle-dz/UniFAR-FTUs huggingface dataset:
Retention of Alzheimer Disease Research Participants

Supplemental Digital Content is available in the text. Introduction: Participant retention is important to maintaining statistical power, minimizing bias, and preventing scientific error in Alzheimer disease and related dementias research. Methods: We surveyed representative investigators from NIH-funded Alzheimer’s Disease Research Centers (ADRC), querying their use of retention tactics across 12 strategies. We compared survey results to data from the National Alzheimer’s Coordinating Center for each center. We used a generalized estimating equation with independent working covariance model and empirical standard errors to assess relationships between survey results and rates of retention, controlling for participant characteristics. Results: Twenty-five (83%) responding ADRCs employed an average 42 (SD=7) retention tactics. In a multivariable model that accounted for participant characteristics, the number of retention tactics used by a center was associated with participant retention (odds ratio=1.68, 95% confidence interval: 1.42, 1.98; P<0.001 for the middle compared with the lowest tertile survey scores; odds ratio=1.59, 95% confidence interval: 1.30, 1.94; P<0.001 for the highest compared with the lowest tertile survey scores) at the first follow-up visit. Participant characteristics such as normal cognition diagnosis, older age, higher education, and Caucasian race were also associated with higher retention. Conclusions: Retention in clinical research is more likely to be achieved by employing a variety of tactics.
Death Anxiety, Religious Doubt, and Depressive Symptoms across Race in Older Adults

The purpose of this study is to investigate the direct and indirect relationships among death anxiety, religious doubt, and depressive symptoms in older adults. This study also investigates race as a moderator for these relationships. This study used data from the Religion, Aging, and Health Survey. Participants identified as Christian, identified as Black or White, lived in a non-institutionalized household within the U.S., were retired, and spoke English. Using PROCESS, results revealed that religious doubt partially mediated the relationship between death anxiety and depressive symptoms. Furthermore, moderated mediation models revealed that race moderated the relationship between religious doubt and depressive symptoms. Specifically, there was significant, positive relationship between religious doubt and depressive symptoms for participants who identified as Black but not White. Results highlight how religious doubt can influence depressive outcomes among the geriatric communities of color. Limitations and future directions are also discussed.
Ten years of the horse reference genome: insights into equine biology, domestication and population dynamics in the post‐genome era

Summary The horse reference genome from the Thoroughbred mare Twilight has been available for a decade and, together with advances in genomics technologies, has led to unparalleled developments in equine genomics. At the core of this progress is the continuing improvement of the quality, contiguity and completeness of the reference genome, and its functional annotation. Recent achievements include the release of the next version of the reference genome (EquCab3.0) and generation of a reference sequence for the Y chromosome. Horse satellite‐free centromeres provide unique models for mammalian centromere research. Despite extremely low genetic diversity of the Y chromosome, it has been possible to trace patrilines of breeds and pedigrees and show that Y variation was lost in the past approximately 2300 years owing to selective breeding. The high‐quality reference genome has led to the development of three different SNP arrays and WGSs of almost 2000 modern individual horses. The collection of WGS of hundreds of ancient horses is unique and not available for any other domestic species. These tools and resources have led to global population studies dissecting the natural history of the species and genetic makeup and ancestry of modern breeds. Most importantly, the available tools and resources, together with the discovery of functional elements, are dissecting molecular causes of a growing number of Mendelian and complex traits. The improved understanding of molecular underpinnings of various traits continues to benefit the health and performance of the horse whereas also serving as a model for complex disease across species.
Clinical Use of a New High-Sensitivity Cardiac Troponin I Assay in Patients with Suspected Myocardial Infarction.

BACKGROUND We aimed to validate the clinical performance of the high-sensitivity cardiac troponin I [VITROS® Immunodiagnostic Products hs Troponin I (hs-cTnI-VITROS)] assay. METHODS We enrolled patients presenting to the emergency department with symptoms suggestive of acute myocardial infarction (AMI). Final diagnoses were centrally adjudicated by 2 independent cardiologists considering all clinical information, including cardiac imaging: first, using serial hs-cTnT-Elecsys (primary analysis) and, second, using hs-cTnI-Architect (secondary analysis) measurements in addition to the clinically used (hs)-cTn. hs-cTnI-VITROS was measured at presentation and at 1 h in a blinded fashion. The primary objective was direct comparison of diagnostic accuracy as quantified by the area under the ROC curve (AUC) of hs-cTnI-VITROS vs hs-cTnT-Elecsys and hs-cTnI-Architect, and in a subgroup also hs-cTnI-Centaur and hs-cTnI-Access. Secondary objectives included the derivation and validation of an hs-cTnI-VITROS-0/1-h algorithm. RESULTS AMI was the adjudicated final diagnosis in 158 of 1231 (13%) patients. At presentation, the AUC for hs-cTnI-VITROS was 0.95 (95% CI, 0.93-0.96); for hs-cTnT-Elecsys, 0.94 (95% CI, 0.92-0.95); and for hs-cTnI-Architect, 0.92 (95% CI, 0.90-0.94). AUCs for hs-cTnI-Centaur and hs-cTnI-Access were 0.95 (95% CI, 0.94-0.97). Applying the derived hs-cTnI-VITROS-0/1-h algorithm (derivation cohort n = 519) to the validation cohort (n = 520), 53% of patients were ruled out [sensitivity, 100% (95% CI, 94.1-100)] and 14% of patients were ruled in [specificity, 95.6% (95% CI, 93.4-97.2)]. Patients ruled out by the 0/1-h algorithm had a survival rate of 99.8% at 30 days. Findings were confirmed in the secondary analyses using the adjudication including serial measurements of hs-cTnI-Architect. CONCLUSIONS The hs-cTnI-VITROS assay has at least comparable diagnostic accuracy with the currently best validated hs-cTnT and hs-cTnI assays.
InDel Marker Based Estimation of Multi-Gene Allele Contribution and Genetic Variations for Grain Size and Weight in Rice (Oryza sativa L.)

The market success of any rice cultivar is exceedingly dependent on its grain appearance, as well as its grain yield, which define its demand by consumers as well as growers. The present study was undertaken to explore the contribution of nine major genes, qPE9~1, GW2, SLG7, GW5, GS3, GS7, GW8, GS5, and GS2, in regulating four size and weight related traits, i.e., grain length (GL), grain width (GW), grain thickness (GT), and thousand grain weight (TGW) in 204 diverse rice germplasms using Insertion/Deletion (InDel) markers. The studied germplasm displayed wide-ranging variability in the four studied traits. Except for three genes, all six genes showed considerable association with these traits with varying strengths. Whole germplasm of 204 genotypes could be categorized into three major clusters with different grain sizes and weights that could be utilized in rice breeding programs where grain appearance and weight are under consideration. The study revealed that TGW was 24.9% influenced by GL, 37.4% influenced by GW, and 49.1% influenced by GT. Hence, assuming the trend of trait selection, i.e., GT > GW > GL, for improving TGW in the rice yield enhancement programs. The InDel markers successfully identified a total of 38 alleles, out of which 27 alleles were major and were found in more than 20 genotypes. GL was associated with four genes (GS3, GS7, GW8, and GS2). GT was also found to be regulated by four different genes (GS3, GS7, GW8, and GS2) out of the nine studied genes. GW was found to be under the control of three studied genes (GW5, GW8, and GS2), whereas TGW was found to be under the influence of four genes (SLG7, GW5, GW8, and GS5) in the germplasm under study. The Unweighted Pair Group Method with Arithmetic means (UPGMA) tree based on the studied InDel marker loci segregated the whole germplasm into three distinct clusters with dissimilar grain sizes and weights. A two-dimensional scatter plot constructed using Principal Coordinate Analysis (PCoA) based on InDel markers further separated the 204 rice germplasms into four sub-populations with prominent demarcations of extra-long, long, medium, and short grain type germplasms that can be utilized in breeding programs accordingly. The present study could help rice breeders to select a suitable InDel marker and in formulation of breeding strategies for improving grain appearance, as well as weight, to develop rice varieties to compete international market demands with higher yield returns. This study also confirms the efficient application of InDel markers in studying diverse types of rice germplasm, allelic frequencies, multiple-gene allele contributions, marker-trait associations, and genetic variations that can be explored further.
New-Onset Refractory Status Epilepticus in Children: Etiologies, Treatments, and Outcomes*

Supplemental Digital Content is available in the text. Objectives: To elucidate etiologies, treatment, functional and neurocognitive outcomes of children with new-onset refractory status epilepticus. Design: A single-center retrospective study. Setting: A tertiary care children’s hospital. Patients: All patients between 1 month and 21 years old admitted with new-onset refractory status epilepticus between January 2004 and July 2017. Interventions: None. Measurements and Main Results: Clinical presentation, laboratory data, imaging studies, and treatments were collected during hospitalization. Outcomes were assessed at hospital discharge and follow-up in the outpatient neurology clinic based on functional and neurocognitive outcomes as well as development of epilepsy. A total of 674 unique patients presented with status epilepticus of which 40 had new-onset refractory status epilepticus. Patients were classified into either refractory status epilepticus or super-refractory status epilepticus. The etiology of most children with new-onset refractory status epilepticus remained cryptogenic. The most common identified etiology was viral (20%). None of the patients had a contributory positive neuronal antibody test. Several treatments were tried including immunotherapy which was used in half of the patients. Five patients died (12.5%) during the acute phase of their disease, with four lost to follow-up. Twenty out of the remaining 31 patients (65%) developed epilepsy and 18 (58%) had persistent neurocognitive impairment. There was no statistical significant difference in various outcome measures and various etiologies, patients’ characteristics, and treatments. Conclusions: In this single-center cohort, more than half of the children with new-onset refractory status epilepticus did not have an identifiable etiology. Unlike adult patients, the presence of positive neuronal antibody syndrome was rare. There was no difference in outcome between those with or without an identifiable etiology. As expected, patients with super-refractory status epilepticus had worse functional and neurocognitive outcomes. More standardized diagnostic and treatment algorithms are needed along with prospective multicenter studies.
Unbiased Thiol-Labeling and Top-Down Proteomic Analyses Implicate Multiple Proteins in the Late Steps of Regulated Secretion

Regulated exocytosis enables temporal and spatial control over the secretion of biologically active compounds; however, the mechanism by which Ca2+ modulates different stages of exocytosis is still poorly understood. For an unbiased, top-down proteomic approach, select thiol- reactive reagents were used to investigate this process in release-ready native secretory vesicles. We previously characterized a biphasic effect of these reagents on Ca2+-triggered exocytosis: low doses potentiated Ca2+ sensitivity, whereas high doses inhibited Ca2+ sensitivity and extent of vesicle fusion. Capitalizing on this novel potentiating effect, we have now identified fluorescent thiol- reactive reagents producing the same effects: Lucifer yellow iodoacetamide, monobromobimane, and dibromobimane. Top-down proteomic analyses of fluorescently labeled proteins from total and cholesterol-enriched vesicle membrane fractions using two-dimensional gel electrophoresis coupled with mass spectrometry identified several candidate targets, some of which have been previously linked to the late steps of regulated exocytosis and some of which are novel. Initial validation studies indicate that Rab proteins are involved in the modulation of Ca2+ sensitivity, and thus the efficiency of membrane fusion, which may, in part, be linked to their previously identified upstream roles in vesicle docking.
Effects of Aspirin or Clopidogrel on Colorectal Cancer Chemoprevention in Patients with Type 2 Diabetes Mellitus

Background: The effect of clopidogrel, whose mechanism of action differs from that of aspirin, on CRC risk remains unknown. We investigated the effects of clopidogrel and aspirin, either as monotherapy or combined, on colorectal cancer (CRC) risk in patients with Type 2 diabetes mellitus (T2DM). Methods: We conducted a cohort study using Taiwan National Health Insurance Research Database. Four groups comprising 218,903 patients using aspirin monotherapy, 20,158 patients using clopidogrel monotherapy, 42,779 patients using dual antiplatelet therapy, and 281,840 nonuser matched controls were created using propensity score matching. Cox proportional hazards regression was used to evaluate the CRC risk during follow-up. Results: During the 13-year follow-up period, we found 9431 cases of CRC over 3,409,522 person-years. The overall incidence rates of CRC were 2.04, 3.45, 1.55, and 3.52 per 1000 person-years in the aspirin, clopidogrel, dual antiplatelet, and nonuser cohorts, respectively. The adjusted hazard ratios (aHRs) were 0.59 (95% confidence interval [CI], 0.56–0.61), 0.77 (95% CI, 0.68–0.87), and 0.37 (95% CI, 0.33–0.40) for the aspirin, clopidogrel, and dual antiplatelet cohorts, respectively. Dose- and duration-dependent chemopreventive effects were observed in the three cohorts.
Short Versus Conventional Pulse‐Width Deep Brain Stimulation in Parkinson's Disease: A Randomized Crossover Comparison

Subthalamic nucleus deep brain stimulation (STN‐DBS) is an effective therapy for selected Parkinson's disease patients with motor fluctuations, but can adversely affect speech and axial symptoms. The use of short pulse width (PW) has been shown to expand the therapeutic window acutely, but its utility in reducing side effects in chronic STN‐DBS patients has not been evaluated.
Size control of the inner ear via hydraulic feedback

Animals make organs of precise size, shape, and symmetry despite noise in underlying molecular and cellular processes. How developing organs manage this noise is largely unknown. Here, we combine quantitative imaging, physical theory, and physiological measurement of hydrostatic pressure and fluid transport in zebrafish to study size control of the developing inner ear. We find that fluid accumulation creates hydrostatic pressure in the lumen leading to stress in the epithelium and expansion of the otic vesicle. Pressure, in turn, inhibits fluid transport into the lumen. This negative feedback loop between pressure and transport allows the otic vesicle to change growth rate to control natural or experimentally-induced size variation. Spatiotemporal patterning of contractility modulates pressure-driven strain for regional tissue thinning. Our work connects moleculardriven mechanisms, such as osmotic pressure driven strain and actomyosin tension, to the regulation of tissue morphogenesis via hydraulic feedback to ensure robust control of organ size.
Cortical morphometry and structural connectivity relate to executive function and estradiol level in healthy adolescents

Emotional and behavioral control is necessary self‐regulatory processes to maintain stable goal‐driven behavior. Studies indicate that variance in these executive function (EF) processes is related to morphological features of the brain and white matter (WM) differences. Furthermore, sex hormone level may modulate circuits in the brain important for cognitive function.
Toward Robust Functional Neuroimaging Genetics of Cognition

A commonly held assumption in cognitive neuroscience is that, because measures of human brain function are closer to underlying biology than distal indices of behavior/cognition, they hold more promise for uncovering genetic pathways. Supporting this view is an influential fMRI-based study of sentence reading/listening by Pinel et al. (2012), who reported that common DNA variants in specific candidate genes were associated with altered neural activation in language-related regions of healthy individuals that carried them. In particular, different single-nucleotide polymorphisms (SNPs) of FOXP2 correlated with variation in task-based activation in left inferior frontal and precentral gyri, whereas a SNP at the KIAA0319/TTRAP/THEM2 locus was associated with variable functional asymmetry of the superior temporal sulcus. Here, we directly test each claim using a closely matched neuroimaging genetics approach in independent cohorts comprising 427 participants, four times larger than the original study of 94 participants. Despite demonstrating power to detect associations with substantially smaller effect sizes than those of the original report, we do not replicate any of the reported associations. Moreover, formal Bayesian analyses reveal substantial to strong evidence in support of the null hypothesis (no effect). We highlight key aspects of the original investigation, common to functional neuroimaging genetics studies, which could have yielded elevated false-positive rates. Genetic accounts of individual differences in cognitive functional neuroimaging are likely to be as complex as behavioral/cognitive tests, involving many common genetic variants, each of tiny effect. Reliable identification of true biological signals requires large sample sizes, power calculations, and validation in independent cohorts with equivalent paradigms. SIGNIFICANCE STATEMENT A pervasive idea in neuroscience is that neuroimaging-based measures of brain function, being closer to underlying neurobiology, are more amenable for uncovering links to genetics. This is a core assumption of prominent studies that associate common DNA variants with altered activations in task-based fMRI, despite using samples (10–100 people) that lack power for detecting the tiny effect sizes typical of genetically complex traits. Here, we test central findings from one of the most influential prior studies. Using matching paradigms and substantially larger samples, coupled to power calculations and formal Bayesian statistics, our data strongly refute the original findings. We demonstrate that neuroimaging genetics with task-based fMRI should be subject to the same rigorous standards as studies of other complex traits.
Incorporating statistical strategy into image analysis to estimate effects of steam and allyl isocyanate on weed control

Weeds are the major limitation to efficient crop production, and effective weed management is necessary to prevent yield losses due to crop-weed competition. Assessments of the relative efficacy of weed control treatments by traditional counting methods is labor intensive and expensive. More efficient methods are needed for weed control assessments. There is extensive literature on advanced techniques of image analysis for weed recognition, identification, classification, and leaf area, but there is limited information on statistical methods for hypothesis testing when data are obtained by image analysis (RGB decimal code). A traditional multiple comparison test, such as the Dunnett-Tukey-Kramer (DTK) test, is not an optimal statistical strategy for the image analysis because it does not fully utilize information contained in RGB decimal code. In this article, a bootstrap method and a Poisson model are considered to incorporate RGB decimal codes and pixels for comparing multiple treatments on weed control. These statistical methods can also estimate interpretable parameters such as the relative proportion of weed coverage and weed densities. The simulation studies showed that the bootstrap method and the Poisson model are more powerful than the DTK test for a fixed significance level. Using these statistical methods, three soil disinfestation treatments, steam, allyl-isothiocyanate (AITC), and control, were compared. Steam was found to be significantly more effective than AITC, a difference which could not be detected by the DTK test. Our study demonstrates that an appropriate statistical method can leverage statistical power even with a simple RGB index.
Comparison of Gene Expression Profiles of Uropathogenic Escherichia Coli CFT073 after Prolonged Exposure to Subinhibitory Concentrations of Different Biocides

Biocides are chemical compounds widely used for sterilization and disinfection. The aim of this study was to examine whether exposure to subinhibitory biocide concentrations influenced transcriptional expression of genes that could improve a pathogen’s drug resistance or fitness. We used DNA microarrays to investigate the transcriptome of the uropathogenic Escherichia coli strain CFT073 in response to prolonged exposure to subinhibitory concentrations of four biocides: benzalkonium chloride, chlorhexidine, hydrogen peroxide and triclosan. Transcription of a gene involved in polymyxin resistance, arnT, was increased after treatment with benzalkonium chloride. However, pretreatment of the bacteria with this biocide did not result in cross-resistance to polymyxin in vitro. Genes encoding products related to transport formed the functional group that was most affected by biocides, as 110 out of 884 genes in this category displayed altered transcription. Transcripts of genes involved in cysteine uptake, sulfate assimilation, dipeptide transport, as well as cryptic phage genes were also more abundant in response to several biocides. Additionally, we identified groups of genes with transcription changes unique to single biocides that might include potential targets for the biocides. The biocides did not increase the resistance potential of the pathogen to other antimicrobials.
RETRACTED ARTICLE: Belinostat suppresses cell proliferation by inactivating Wnt/β-catenin pathway and promotes apoptosis through regulating PKC pathway in breast cancer

We, the Editors and Publisher of the journal Artificial Cells, Nanomedicine, and Biotechnology, have retracted the following article: Pengwei Lu, Yuanting Gu, Lin Li, Fang Wang, Xue Yang & Yunqing Yang (2019) Belinostat suppresses cell proliferation by inactivating Wnt/β-catenin pathway and promotes apoptosis through regulating PKC pathway in breast cancer. Artificial Cells, Nanomedicine, and Biotechnology, 47(1), 3955–3960, DOI: 10.1080/21691401.2019. 1671855 Since publication, concerns have been raised about the integrity of the data in the article. When approached for an explanation, the authors checked their data and confirmed there are fundamental errors present. Therefore, they have agreed to the retraction of this article. The authors apologise for this oversight. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.