Miracle-dz/UniFAR-FTUs huggingface dataset:
Bioassay-Guided Isolation and Identification of Xanthine Oxidase Inhibitory Constituents from the Leaves of Perilla frutescens

Activity-directed fractionation and purification processes were employed to identify xanthine oxidase (XO) inhibitory compounds from the leaves of Perilla frutescens. The total extract was evaluated in vitro on XO inhibitory activity and in vivo in an experimental model with potassium oxonate-induced hyperuricemia in mice which was used to evaluate anti-hyperuricemic activity. The crude extract showed expressive urate-lowering activity results. Solvent partitioning of the total extract followed by macroporous resin column chromatography of the n-butanol extract yielded four extracts and eluted parts. Among them, only the 70% ethanol eluted part of the n-butanol extract showed strong activity and therefore was subjected to separation and purification using various chromatographic techniques. Five compounds showing potent activity were identified by comparing their spectral data with literature values to be caffeic acid, vinyl caffeate, rosmarinic acid, methyl rosmarinate, and apigenin. These results indicate that pending further study, these compounds could be used as novel natural product agents for the treatment of hyperuricemia.
Xpert MTB/Rif for the diagnosis of extrapulmonary tuberculosis – an experience from a tertiary care centre in South India

The Xpert MTB/Rif, with a detection limit of 131 CFU/ml, plays a valuable role in the diagnosis of extrapulmonary tuberculosis, both susceptible and resistant. This study aims at evaluating the Xpert MTB/Rif for the same, at a tertiary care centre in south India, assessing it against both culture and a composite gold standard (CGS).
On the Random Satisfiable Process

In this work we suggest a new model for generating random satisfiable k-CNF formulas. To generate such formulas. randomly permute all $2^k\binom{n}{k}$ possible clauses over the variables x1,. ,xn, and starting from the empty formula, go over the clauses one by one, including each new clause as you go along if, after its addition, the formula remains satisfiable. We study the evolution of this process, namely the distribution over formulas obtained after scanning through the first m clauses (in the random permutation's order). Random processes with conditioning on a certain property being respected are widely studied in the context of graph properties. This study was pioneered by Ruciński and Wormald in 1992 for graphs with a fixed degree sequence, and also by Erdős, Suen and Winkler in 1995 for triangle-free and bipartite graphs. Since then many other graph properties have been studied, such as planarity and H-freeness. Thus our model is a natural extension of this approach to the satisfiability setting. Our main contribution is as follows. For m ≥ cn, c = c(k) a sufficiently large constant, we are able to characterize the structure of the solution space of a typical formula in this distribution. Specifically, we show that typically all satisfying assignments are essentially clustered in one cluster, and all but e−Ω(m/n)n of the variables take the same value in all satisfying assignments. We also describe a polynomial-time algorithm that finds w.h. p. a satisfying assignment for such formulas.
Learning with the weighted trace-norm under arbitrary sampling distributions

We provide rigorous guarantees on learning with the weighted trace-norm under arbitrary sampling distributions. We show that the standard weighted-trace norm might fail when the sampling distribution is not a product distribution (i.e. when row and column indexes are not selected independently), present a corrected variant for which we establish strong learning guarantees, and demonstrate that it works better in practice. We provide guarantees when weighting by either the true or empirical sampling distribution, and suggest that even if the true distribution is known (or is uniform), weighting by the empirical distribution may be beneficial.
The Temporal Impulse Response Underlying Saccadic Decisions

Models of perceptual decision making often assume that sensory evidence is accumulated over time in favor of the various possible decisions, until the evidence in favor of one of them outweighs the evidence for the others. Saccadic eye movements are among the most frequent perceptual decisions that the human brain performs. We used stochastic visual stimuli to identify the temporal impulse response underlying saccadic eye movement decisions. Observers performed a contrast search task, with temporal variability in the visual signals. In experiment 1, we derived the temporal filter observers used to integrate the visual information. The integration window was restricted to the first ∼100 ms after display onset. In experiment 2, we showed that observers cannot perform the task if there is no useful information to distinguish the target from the distractor within this time epoch. We conclude that (1) observers did not integrate sensory evidence up to a criterion level, (2) observers did not integrate visual information up to the start of the saccadic dead time, and (3) variability in saccade latency does not correspond to variability in the visual integration period. Instead, our results support a temporal filter model of saccadic decision making. The temporal impulse response identified by our methods corresponds well with estimates of integration times of V1 output neurons.
GemC1 governs multiciliogenesis through direct interaction with and transcriptional regulation of p73

ABSTRACT A distinct combination of transcription factors elicits the acquisition of a specific fate and the initiation of a differentiation program. Multiciliated cells (MCCs) are a specialized type of epithelial cells that possess dozens of motile cilia on their apical surface. Defects in cilia function have been associated with ciliopathies that affect many organs, including brain and airway epithelium. Here we show that the geminin coiled-coil domain-containing protein 1 GemC1 (also known as Lynkeas) regulates the transcriptional activation of p73, a transcription factor central to multiciliogenesis. Moreover, we show that GemC1 acts in a trimeric complex with transcription factor E2F5 and tumor protein p73 (officially known as TP73), and that this complex is important for the activation of the p73 promoter. We also provide in vivo evidence that GemC1 is necessary for p73 expression in different multiciliated epithelia. We further show that GemC1 regulates multiciliogenesis through the control of chromatin organization, and the epigenetic marks/tags of p73 and Foxj1. Our results highlight novel signaling cues involved in the commitment program of MCCs across species and tissues. This article has an associated First Person interview with the first author of the paper. Highlighted Article: GemC1 within the trimeric GemC1–E2F5–p73 complex regulates transcriptional activation of p73 and modifies the chromatin organization of the p73 locus in order to generate multiciliated cells.
PlnTFDB: updated content and new features of the plant transcription factor database

The Plant Transcription Factor Database (PlnTFDB; http://plntfdb.bio.uni-potsdam.de/v3.0/) is an integrative database that provides putatively complete sets of transcription factors (TFs) and other transcriptional regulators (TRs) in plant species (sensu lato) whose genomes have been completely sequenced and annotated. The complete sets of 84 families of TFs and TRs from 19 species ranging from unicellular red and green algae to angiosperms are included in PlnTFDB, representing >1.6 billion years of evolution of gene regulatory networks. For each gene family, a basic description is provided that is complemented by literature references, and multiple sequence alignments of protein domains. TF or TR gene entries include information of expressed sequence tags, 3D protein structures of homologous proteins, domain architecture and cross-links to other computational resources online. Moreover, the different species in PlnTFDB are linked to each other by means of orthologous genes facilitating cross-species comparisons.
Interventions to Decrease Use in Prehospital and Emergency Care Settings Among Super-Utilizers in the United States: A Systematic Review

Interest in high users of acute care continues to grow as health care organizations look to deliver cost-effective and high-quality care to patients. Since “super-utilizers” of acute care are responsible for disproportionately high health care spending, many programs and interventions have been implemented to reduce medical care use and costs in this population. This article presents a systematic review of the peer-reviewed and grey literature on evaluations of interventions to decrease prehospital and emergency care use among U.S. super-utilizers. Forty-six distinct evaluations were included in the review. The most commonly evaluated intervention was case management. Although a number of interventions reported reductions in prehospital and emergency care utilization and costs, methodological and study design weaknesses—especially regression to the mean—were widespread and call into question reported positive findings. More high-quality research is needed to accurately assess the impact of interventions to reduce prehospital and emergency care use in the super-utilizer population.
Binding site‐based classification of coronaviral papain‐like proteases†

The coronavirus replicase gene encodes one or two papain‐like proteases (termed PL1pro and PL2pro) implicated in the N‐terminal processing of the replicase polyprotein and thus contributing to the formation of the viral replicase complex that mediates genome replication. Using consensus fold recognition with the 3D‐JURY meta‐predictor followed by model building and refinement, we developed a structural model for the single PLpro present in the severe acute respiratory syndrome coronavirus (SCoV) genome, based on significant structural relationships to the catalytic core domain of HAUSP, a ubiquitin‐specific protease (USP). By combining the SCoV PLpro model with comparative sequence analyses we show that all currently known coronaviral PLpros can be classified into two groups according to their binding site architectures. One group includes all PL2pros and some of the PL1pros, which are characterized by a restricted USP‐like binding site. This group is designated the R‐group. The remaining PL1pros from some of the coronaviruses form the other group, featuring a more open papain‐like binding site, and is referred to as the O‐group. This two‐group, binding site‐based classification is consistent with experimental data accumulated to date for the specificity of PLpro‐mediated polyprotein processing and PLpro inhibition. It also provides an independent evaluation of the similarity‐based annotation of PLpro‐mediated cleavage sites, as well as a basis for comparison with previous groupings based on phylogenetic analyses. Proteins 2006.
Fluoxetine v. placebo in prevention of relapse in post-traumatic stress disorder

Background Little is known about the effect of pharmacotherapy in the prevention of post-traumatic stress disorder (PTSD) relapse. Aims To assess the efficacy and tolerability of fluoxetine in preventing PTSD relapse. Method This was a double-blind, randomised, placebo-controlled study. Following 12 weeks of acute treatment, patients who responded were re-randomised and continued in a 24-week relapse prevention phase with fluoxetine (n=69) or placebo (n=62). The primary efficacy assessment was the prevention of PTSD relapse, based on the time to relapse. Results Patients in the fluoxetine/fluoxetine group were less likely to relapse than patients in the fluoxetine/placebo group (P=0.027). There were no clinically significant differences in treatment-emergent adverse events between treatment groups. Conclusions Fluoxetine is effective and well tolerated in the prevention of PTSD relapse for up to 6 months.
Soft tubular microfluidics for 2D and 3D applications

Significance The current cleanroom-based soft lithography microfabrication process is complicated and expensive. There is a need for low-cost, ready-to-use, modular components that can be easily assembled into microfluidic devices by users lacking proficiency or access to microfabrication facilities. We present a facile, low-cost, and efficient method of fabricating soft, elastic microtubes with different cross-sectional shapes and dimensions. These microtubes can be used as basic building blocks for the rapid construction of various 2D and 3D microfluidic devices with complex geometries, topologies, and functions. This approach avoids the conventional cumbersome photolithography process and thus, provides a feasible way for scaling up the production of microfluidic devices. Microfluidics has been the key component for many applications, including biomedical devices, chemical processors, microactuators, and even wearable devices. This technology relies on soft lithography fabrication which requires cleanroom facilities. Although popular, this method is expensive and labor-intensive. Furthermore, current conventional microfluidic chips precludes reconfiguration, making reiterations in design very time-consuming and costly. To address these intrinsic drawbacks of microfabrication, we present an alternative solution for the rapid prototyping of microfluidic elements such as microtubes, valves, and pumps. In addition, we demonstrate how microtubes with channels of various lengths and cross-sections can be attached modularly into 2D and 3D microfluidic systems for functional applications. We introduce a facile method of fabricating elastomeric microtubes as the basic building blocks for microfluidic devices. These microtubes are transparent, biocompatible, highly deformable, and customizable to various sizes and cross-sectional geometries. By configuring the microtubes into deterministic geometry, we enable rapid, low-cost formation of microfluidic assemblies without compromising their precision and functionality. We demonstrate configurable 2D and 3D microfluidic systems for applications in different domains. These include microparticle sorting, microdroplet generation, biocatalytic micromotor, triboelectric sensor, and even wearable sensing. Our approach, termed soft tubular microfluidics, provides a simple, cheaper, and faster solution for users lacking proficiency and access to cleanroom facilities to design and rapidly construct microfluidic devices for their various applications and needs.
Distance and near visual acuity, contrast sensitivity, and visual fields of 10-year-old children.

OBJECTIVE To measure monocular distance visual acuity, near visual acuity, contrast sensitivity, and visual field extent in full-term, 10-year-old children tested according to the protocol used to test 10-year-old preterm children in the Cryotherapy for Retinopathy of Prematurity study. SUBJECTS AND METHODS Subjects were 106 healthy, full-term children, 9.8 to 10.9 years of age, who had no ocular abnormalities other than ametropia. All were tested monocularly using Early Treatment and Diabetic Retinopathy Study distance and near visual acuity charts and Pelli-Robson contrast sensitivity charts, with refractive error corrected according to Cryotherapy for Retinopathy of Prematurity study criteria. Goldmann perimetry was tested without correction using the V-4-e and III-4-e stimuli along 8 meridia. A standard pediatric eye examination was performed on each subject. RESULTS Mean (SD) distance visual acuity was 20/19.6 OD (0.082 log unit [lu]) and mean near visual acuity was 20/19.5 OD (0.100 lu). Mean (SD) contrast sensitivity was 1.69 OD (0.12 lu), with a mean (SD) of 36.4 (2.2) letters read. Visual field extent was larger for the V-4-e stimulus than for the III-4-e stimulus. CONCLUSIONS The results provide the first monocular normative data from a large sample of 10-year-old children tested with Early Treatment and Diabetic Retinopathy Study distance and near visual acuity charts and the Pelli-Robson contrast sensitivity charts, and add to the literature on Goldmann perimetry in children.
Electronic Discovery and Electronic Medical Records : Does the Threat of Litigation affect Firm Decisions to Adopt Technology ?

Firms’ decision-making is increasingly leaving an electronic trail. We ask how the threat of litigation affects decisions to adopt technologies that leave more of an electronic trail, like electronic medical records (EMR). On the one hand, firms may embrace a technology that allows them to easily document that their actions were appropriate if they have to defend them in court. On the other hand, firms may fear that the ease of ‘electronic discovery’ may increase their exposure to potentially costly litigation. EMRs allow hospitals to document electronically both patient symptoms and the health providers’ reactions to those symptoms. We find evidence that hospitals are 33 percent less likely to adopt electronic medical records if there are state laws that facilitate the use of electronic records in court. ∗Economics Department, University of Virginia, Charlottesville, VA †MIT Sloan School of Business, MIT, Cambridge, MA. ‡We thank HIMSS Analytics for providing the data used in this study. All errors are our own.
Characterization of the Paracoccidioides Hypoxia Response Reveals New Insights into Pathogenesis Mechanisms of This Important Human Pathogenic Fungus

Background Hypoxic microenvironments are generated during fungal infection. It has been described that to survive in the human host, fungi must also tolerate and overcome in vivo microenvironmental stress conditions including low oxygen tension; however nothing is known how Paracoccidioides species respond to hypoxia. The genus Paracoccidioides comprises human thermal dimorphic fungi and are causative agents of paracoccidioidomycosis (PCM), an important mycosis in Latin America. Methodology/Principal Findings In this work, a detailed hypoxia characterization was performed in Paracoccidioides. Using NanoUPLC-MSE proteomic approach, we obtained a total of 288 proteins differentially regulated in 12 and 24 h of hypoxia, providing a global view of metabolic changes during this stress. In addition, a functional characterization of the homologue to the most important molecule involved in hypoxia responses in other fungi, the SREBP (sterol regulatory element binding protein) was performed. We observed that Paracoccidioides species have a functional homologue of SREBP, named here as SrbA, detected by using a heterologous genetic approach in the srbA null mutant in Aspergillus fumigatus. Paracoccidioides srbA (PbsrbA), in addition to involvement in hypoxia, is probable involved in iron adaptation and azole drug resistance responses. Conclusions/Significance In this study, the hypoxia was characterized in Paracoccidioides. The first results can be important for a better understanding of the fungal adaptation to the host and improve the arsenal of molecules for the development of alternative treatment options in future, since molecules related to fungal adaptation to low oxygen levels are important to virulence and pathogenesis in human pathogenic fungi.
Hypertension as a Risk Factor for Diabetic Neuropathy: A Prospective Study

The pathogeneses of diabetic neuropathy is still unclear. This study prospectively investigated the risk factors for distal symmetrical polyneuropathy (DSP) in a cohort of childhood-onset IDDM patients. Subjects from the Epidemiology of Diabetes Complications (EDC) Study were clinically examined at baseline and then biennially. DSP was diagnosed by a combination of clinical criteria, symptoms and signs (Diabetes Control and Complications Trial [DCCT] exam), and quantitative sensory threshold (QST). Among the 463 (70.4%) subjects who were free of DSP at baseline, 453 (97.8%) participated in at least one biennial reexamination during the first 6 years of follow-up and were included in the current analysis. A total of 68 (15.0%) subjects developed DSP in 6 years, giving a cumulative probability of 0.29. The Cox proportional hazards model shows that longer IDDM duration, hypertension, poor glycemic control, height, and smoking were all independent predictors of the incidence of DSP (all P < 0.0001, except for smoking for which P = 0.03). Hypertension showed the greatest impact on the development of DSP for individuals with either short or long IDDM duration. This study confirms some risk factors for DSP found in crosssectional studies and suggests a strong relationship between hypertension and DSP. The results indicate that in addition to good glycemic control, avoidance of smoking and good blood pressure control may be helpful in preventing or delaying the onset of DSP in IDDM patients.
The Evidence

Supported employment for people with severe mental illness is an evi-dence-based practice, based on converging findings from eight randomized controlled trials and three quasi-experimental studies. The critical ingredients of supported employment have been well described, and a fidelity scale differentiates supported employment programs from other types of vocational services. The effectiveness of supported employment appears to be generalizable across a broad range of client characteristics and community settings. More research is needed on long-term outcomes and on cost-effectiveness. Access to supported employment programs remains a problem, despite their increasing use throughout the United States. The authors discuss barriers to implementation and strategies for overcoming them
Global Analysis of Genetic, Epigenetic and Transcriptional Polymorphisms in Arabidopsis thaliana Using Whole Genome Tiling Arrays

Whole genome tiling arrays provide a high resolution platform for profiling of genetic, epigenetic, and gene expression polymorphisms. In this study we surveyed natural genomic variation in cytosine methylation among Arabidopsis thaliana wild accessions Columbia (Col) and Vancouver (Van) by comparing hybridization intensity difference between genomic DNA digested with either methylation-sensitive (HpaII) or -insensitive (MspI) restriction enzyme. Single Feature Polymorphisms (SFPs) were assayed on a full set of 1,683,620 unique features of Arabidopsis Tiling Array 1.0F (Affymetrix), while constitutive and polymorphic CG methylation were assayed on a subset of 54,519 features, which contain a 5'CCGG3' restriction site. 138,552 SFPs (1% FDR) were identified across enzyme treatments, which preferentially accumulated in pericentromeric regions. Our study also demonstrates that at least 8% of all analyzed CCGG sites were constitutively methylated across the two strains, while about 10% of all analyzed CCGG sites were differentially methylated between the two strains. Within euchromatin arms, both constitutive and polymorphic CG methylation accumulated in central regions of genes but under-represented toward the 5' and 3' ends of the coding sequences. Nevertheless, polymorphic methylation occurred much more frequently in gene ends than constitutive methylation. Inheritance of methylation polymorphisms in reciprocal F1 hybrids was predominantly additive, with F1 plants generally showing levels of methylation intermediate between the parents. By comparing gene expression profiles, using matched tissue samples, we found that magnitude of methylation polymorphism immediately upstream or downstream of the gene was inversely correlated with the degree of expression variation for that gene. In contrast, methylation polymorphism within genic region showed weak positive correlation with expression variation. Our results demonstrated extensive genetic and epigenetic polymorphisms between Arabidopsis accessions and suggested a possible relationship between natural CG methylation variation and gene expression variation.