Miracle-dz/UniFAR-FTUs huggingface dataset:
Single-cell regulome data analysis by SCRAT

Abstract Summary Emerging single-cell technologies (e.g. single-cell ATAC-seq, DNase-seq or ChIP-seq) have made it possible to assay regulome of individual cells. Single-cell regulome data are highly sparse and discrete. Analyzing such data is challenging. User-friendly software tools are still lacking. We present SCRAT, a Single-Cell Regulome Analysis Toolbox with a graphical user interface, for studying cell heterogeneity using single-cell regulome data. SCRAT can be used to conveniently summarize regulatory activities according to different features (e.g. gene sets, transcription factor binding motif sites, etc.). Using these features, users can identify cell subpopulations in a heterogeneous biological sample, infer cell identities of each subpopulation, and discover distinguishing features such as gene sets and transcription factors that show different activities among subpopulations. Availability and implementation SCRAT is freely available at https://zhiji.shinyapps. io/scrat as an online web service and at https://github.com/zji90/SCRAT as an R package. Supplementary information Supplementary data are available at Bioinformatics online.
Staphylococcus aureus Colonization Induces Strain-Specific Suppression of Interleukin-17

ABSTRACT Staphylococcus aureus is a pathogen that causes significant morbidity and mortality. Nasal carriage is a major source of transmission and of endogenous infection. Persistent carriage is detected in ∼30% of healthy individuals. While Th17 cells have been shown to play a role in S. aureus infection and clearance, the immune response to carriage is not well understood. Here, we evaluate the Th17 response and its potential inhibitors during S. aureus carriage. We recruited 25 volunteers, of whom 11 were persistent carriers. Volunteers' peripheral blood mononuclear cells (PBMCs) were stimulated with either their endogenous strain (a strain isolated from that carrier) or exogenous ones (strains not carried by that volunteer). Changes in Th17 cell frequency and numbers, interleukin-17 (IL-17) mRNA expression, and IL-17 protein abundance were measured by fluorescence-activated cell sorting, real-time PCR, and enzyme-linked immunosorbent assay. Similarly, responses of IL-17 suppressors (regulatory T cells [FOXP3], IL-10, IL-27, and IL-19) were measured. Th17 and IL-17 levels in response to stimulation with endogenous strains were significantly lower than those in response to stimulation with exogenous ones. Of the suppressive cytokines tested, only IL-19 exhibited a stronger response to endogenous than to exogenous strains. Addition of recombinant IL-19 to exogenous-strain-stimulated PBMCs caused decreased IL-17 expression, whereas addition of IL-19 antibodies to endogenous-strain-stimulated cells resulted in an increased IL-17 response. Together, our results suggest that S. aureus carriage induced a tolerogenic response to a carried strain that could be reproduced through the addition of recombinant IL-19 or prevented by the addition of IL-19 antibodies. This differential immune response may play a role in the determination of S. aureus carriage patterns.
Acutely damaged axons are remyelinated in multiple sclerosis and experimental models of demyelination

Remyelination is in the center of new therapies for the treatment of multiple sclerosis to resolve and improve disease symptoms and protect axons from further damage. Although remyelination is considered beneficial in the long term, it is not known, whether this is also the case early in lesion formation. Additionally, the precise timing of acute axonal damage and remyelination has not been assessed so far. To shed light onto the interrelation between axons and the myelin sheath during de‐ and remyelination, we employed cuprizone‐ and focal lysolecithin‐induced demyelination and performed time course experiments assessing the evolution of early and late stage remyelination and axonal damage. We observed damaged axons with signs of remyelination after cuprizone diet cessation and lysolecithin injection. Similar observations were made in early multiple sclerosis lesions. To assess the correlation of remyelination and axonal damage in multiple sclerosis lesions, we took advantage of a cohort of patients with early and late stage remyelinated lesions and assessed the number of APP‐ and SMI32‐ positive damaged axons and the density of SMI31‐positive and silver impregnated preserved axons. Early de‐ and remyelinating lesions did not differ with respect to axonal density and axonal damage, but we observed a lower axonal density in late stage demyelinated multiple sclerosis lesions than in remyelinated multiple sclerosis lesions. Our findings suggest that remyelination may not only be protective over a long period of time, but may play an important role in the immediate axonal recuperation after a demyelinating insult.
Improved quantum backtracking algorithms through effective resistance estimates

We investigate quantum backtracking algorithms of a type previously introduced by Montanaro (arXiv:1509.02374). These algorithms explore trees of unknown structure, and in certain cases exponentially outperform classical procedures (such as DPLL). Some of the previous work focused on obtaining a quantum advantage for trees in which a unique marked vertex is promised to exist. We remove this restriction and re-characterise the problem in terms of the effective resistance of the search space. To this end, we present a generalisation of one of Montanaro's algorithms to trees containing $k \geq 1$ marked vertices, where $k$ is not necessarily known \textit{a priori}. Our approach involves using amplitude estimation to determine a near-optimal weighting of a diffusion operator, which can then be applied to prepare a superposition state that has support only on marked vertices and ancestors thereof. By repeatedly sampling this state and updating the input vertex, a marked vertex is reached in a logarithmic number of steps. The algorithm thereby achieves the conjectured bound of $\widetilde{\mathcal{O}}(\sqrt{TR_{\mathrm{max}}})$ for finding a single marked vertex and $\widetilde{\mathcal{O}}\left(k\sqrt{T R_{\mathrm{max}}}\right)$ for finding all $k$ marked vertices, where $T$ is an upper bound on the tree size and $R_{\mathrm{max}}$ is the maximum effective resistance encountered by the algorithm. This constitutes a speedup over Montanaro's original procedure in both the case of finding one and finding multiple marked vertices in an arbitrary tree. If there are no marked vertices, the effective resistance becomes infinite, and we recover the scaling of Montanaro's existence algorithm.
Sinophysis and Pseudophalacroma are Distantly Related to Typical Dinophysoid Dinoflagellates (Dinophysales, Dinophyceae)

Dinophysoid dinoflagellates are usually considered a large monophyletic group. Large subunit and small subunit (SSU) rDNA phylogenies suggest a basal position for Amphisoleniaceae (Amphisolenia,Triposolenia) with respect to two sister groups, one containing most Phalacroma species plus Oxyphysis and the other Dinophysis,Ornithocercus, Dinophysoid dinoflagellates are usually considered a large monophyletic group. Large subunit and small subunit (SSU) rDNA phylogenies suggest a basal position for Amphisoleniaceae (Amphisolenia,Triposolenia) with respect to two sister groups, one containing most Phalacroma species plus Oxyphysis and the other Dinophysis,Ornithocercus, Histioneis,Citharistes and some Phalacroma species. We provide here new SSU rDNA sequences of Pseudophalacroma (pelagic) and Sinophysis (the only benthic dinophysoid genus). Molecular phylogenies support that they are very divergent with respect to the main clade of Dinophysales. Additional molecular markers of these two key genera are needed to elucidate the evolutionary relations among the dinophysoid dinoflagellates.
Fully convolutional neural networks improve abdominal organ segmentation

Abdominal image segmentation is a challenging, yet important clinical problem. Variations in body size, position, and relative organ positions greatly complicate the segmentation process. Historically, multi-atlas methods have achieved leading results across imaging modalities and anatomical targets. However, deep learning is rapidly overtaking classical approaches for image segmentation. Recently, Zhou et al. showed that fully convolutional networks produce excellent results in abdominal organ segmentation of computed tomography (CT) scans. Yet, deep learning approaches have not been applied to whole abdomen magnetic resonance imaging (MRI) segmentation. Herein, we evaluate the applicability of an existing fully convolutional neural network (FCNN) designed for CT imaging to segment abdominal organs on T2 weighted (T2w) MRI’s with two examples. In the primary example, we compare a classical multi-atlas approach with FCNN on forty-five T2w MRI’s acquired from splenomegaly patients with five organs labeled (liver, spleen, left kidney, right kidney, and stomach). Thirty-six images were used for training while nine were used for testing. The FCNN resulted in a Dice similarity coefficient (DSC) of 0.930 in spleens, 0.730 in left kidneys, 0.780 in right kidneys, 0.913 in livers, and 0.556 in stomachs. The performance measures for livers, spleens, right kidneys, and stomachs were significantly better than multi-atlas (p < 0.05, Wilcoxon rank-sum test). In a secondary example, we compare the multi-atlas approach with FCNN on 138 distinct T2w MRI’s with manually labeled pancreases (one label). On the pancreas dataset, the FCNN resulted in a median DSC of 0.691 in pancreases versus 0.287 for multi-atlas. The results are highly promising given relatively limited training data and without specific training of the FCNN model and illustrate the potential of deep learning approaches to transcend imaging modalities. 1
Early low‐dose erythropoiesis‐stimulating agent therapy and progression of moderate chronic kidney disease: a randomized, placebo‐controlled trial

Background. It is unknown whether early intervention with low‐dose erythropoiesis‐stimulating agents (ESAs) in non‐anaemic patients delays progression of chronic kidney disease (CKD). Methods. In a single‐blind, 24‐month trial, adults with estimated glomerular filtration rate (eGFR) 30‐59 mL/min/1.73 m2 and either Type 2 diabetes mellitus or previous kidney transplantation were randomized to low‐dose continuous erythropoiesis receptor activator (CERA; monthly dose 30‐75 &mgr;g; n = 115) or placebo (n = 120). The primary endpoint was the annual change in eGFR (abbreviated Modification of Diet in Renal Disease formula). Results. Mean (standard deviation) eGFR was 40.7 (9.8) mL/min/1.73 m2 versus 39.8 (9.2) mL/min/1.73 m2 at baseline for CERA and placebo, respectively, and 39.0 (11.6) g/dL versus 39.7 (10.6) g/dL at the final visit. The median (interquartile range) annual reduction in eGFR was 0.5 (−2.2, 3.8) mL/min/1.73 m2 with CERA versus 0.4 (−2.0, 3.2) mL/min/1.73 m2 with placebo (P = 0.657). No significant difference in the annual change in eGFR was observed between treatment groups in the subpopulations with Type 2 diabetes or kidney transplant. Adverse events with a suspected relation to study drug occurred in 22.0% and 16.2% of patients randomized to CERA or placebo, respectively, and adverse events led to study drug discontinuation in 11.0% and 8.5% of patients. Conclusions. Patients with moderate CKD and Type 2 diabetes or previous kidney transplantation showed stable renal function that was unaffected by administration of low‐dose ESA. In addition, there was no clinically meaningful effect of 2‐year low‐dose ESA treatment on albuminuria, an important surrogate marker of kidney injury.
Pseudomonas aeruginosa MutL promotes large chromosomal deletions through non-homologous end joining to prevent bacteriophage predation

Abstract Pseudomonas aeruginosa is an opportunistic pathogen with a relatively large genome, and has been shown to routinely lose genomic fragments during environmental selection. However, the underlying molecular mechanisms that promote chromosomal deletion are still poorly understood. In a recent study, we showed that by deleting a large chromosomal fragment containing two closely situated genes, hmgA and galU, P. aeruginosa was able to form ‘brown mutants’, bacteriophage (phage) resistant mutants with a brown color phenotype. In this study, we show that the brown mutants occur at a frequency of 227 ± 87 × 10−8 and contain a deletion ranging from ∼200 to ∼620 kb. By screening P. aeruginosa transposon mutants, we identified mutL gene whose mutation constrained the emergence of phage-resistant brown mutants. Moreover, the P. aeruginosa MutL (PaMutL) nicking activity can result in DNA double strand break (DSB), which is then repaired by non-homologous end joining (NHEJ), leading to chromosomal deletions. Thus, we reported a noncanonical function of PaMutL that promotes chromosomal deletions through NHEJ to prevent phage predation.
Planning of joint trajectories for humanoid robots using B-spline wavelets

The formulation and optimization of joint trajectories for humanoid robots is quite different from this same task for standard robots because of the complexity of the humanoid robots' kinematics. We exploit the similarity between the movements of a humanoid robot and human movements to generate joint trajectories for such robots. In particular we show how to transform human motion information captured by an optical tracking device into a high dimensional trajectory of a humanoid robot. We utilize B-spline wavelets to efficiently represent the joint trajectories and to automatically select the density of the basis functions on the time axis. We applied our method to the task of teaching a humanoid robot how to make a dance movement.
Thy1‐YFP‐H Mice and the Parallel Rod Floor Test to Evaluate Short‐ and Long‐Term Progression of Traumatic Brain Injury

Traumatic brain injury (TBI) is a leading cause of death and disability and is a risk factor for the later development of neuropsychiatric disorders and neurodegenerative diseases. Many models of TBI have been developed, but their further refinement and a more detailed long‐term follow‐up is needed. We have used the Thy1‐YFP‐H transgenic mouse line and the parallel rod floor test to produce an unbiased and robust method for the evaluation of the multiple effects of a validated model of controlled cortical injury. This approach reveals short‐ and long‐term progressive changes, including compromised biphasic motor function up to 85 days post‐lesion, which correlates with neuronal atrophy, dendrite and spine loss, and long‐term axonal pathology evidenced by axon spheroids and fragmentation. Here we present methods for inducing a controlled cortical injury in the Thy1‐YFP‐H transgenic mouse line and for evaluating the resulting deficits in the parallel rod floor test. This technique constitutes a new, unbiased, and robust method for the evaluation of motor and behavioral alterations after TBI. © 2018 by John Wiley & Sons, Inc.
Prevalence of anaemia, deficiencies of iron and vitamin A and their determinants in rural women and young children: a cross-sectional study in Kalalé district of northern Benin

Abstract Objective To identify the magnitude of anaemia and deficiencies of Fe (ID) and vitamin A (VAD) and their associated factors among rural women and children. Design Cross-sectional, comprising a household, health and nutrition survey and determination of Hb, biochemical (serum concentrations of ferritin, retinol, C-reactive protein and α1-acid glycoprotein) and anthropometric parameters. Multivariate logistic regression examined associations of various factors with anaemia and micronutrient deficiencies. Setting Kalalé district, northern Benin. Subjects Mother–child pairs (n 767): non-pregnant women of reproductive age (15–49 years) and children 6–59 months old. Results In women, the overall prevalence of anaemia, ID, Fe-deficiency anaemia (IDA) and VAD was 47·7, 18·3, 11·3 and 17·7 %, respectively. A similar pattern for anaemia (82·4 %), ID (23·6 %) and IDA (21·2 %) was observed among children, while VAD was greater at 33·6 %. Greater risk of anaemia, ID and VAD was found for low maternal education, maternal farming activity, maternal health status, low food diversity, lack of fruits and vegetables consumption, low protein foods consumption, high infection, anthropometric deficits, large family size, poor sanitary conditions and low socio-economic status. Strong differences were also observed by ethnicity, women’s group participation and source of information. Finally, age had a significant effect in children, with those aged 6–23 months having the highest risk for anaemia and those aged 12–23 months at risk for ID and IDA. Conclusions Anaemia, ID and VAD were high among rural women and their children in northern Benin, although ID accounted for a small proportion of anaemia. Multicentre studies in various parts of the country are needed to substantiate the present results, so that appropriate and beneficial strategies for micronutrient supplementation and interventions to improve food diversity and quality can be planned.
Experiences of and barriers to transition-related healthcare among Korean transgender adults: focus on gender identity disorder diagnosis, hormone therapy, and sex reassignment surgery

OBJECTIVES Transgender people may encounter barriers to transition-related healthcare services. This study aimed to investigate the experiences of transition-related healthcare and barriers to those procedures among transgender adults in Korea. METHODS In 2017, we conducted a nationwide cross-sectional survey of 278 transgender adults, which named Rainbow Connection Project II, in Korea. We assessed the prevalence of transition-related healthcare, including gender identity disorder (GID) diagnosis, hormone therapy, and sex reassignment surgery. To understand the barriers to those procedures, we also asked participants for their reasons for not receiving each procedure. Further, this study examined their experiences of and the reasons for using non-prescribed hormone medications. RESULTS Of transgender people participated in the survey, 91.0% (n=253/278) were diagnosed with GID, 88.0% (n=243/276) received hormone therapy, and 42.4% (n=115/271) have had any kind of sex reassignment surgery. Cost was the most common barrier to transition-related healthcare among Korean transgender adults. Other common barriers were identified as follows: negative experiences in healthcare settings, lack of specialized healthcare professionals and facilities, and social stigma against transgender people. Among those who had taken hormone medications, 25.1% (n=61/243) reported that they had ever purchased them without a prescription. CONCLUSIONS Our findings suggest that barriers to transition-related healthcare exist in Korea and constrain transgender individuals’ safe access to the needed healthcare. Institutional interventions are strongly recommended to improve access to transition-related healthcare. These interventions include provision of programs to train Korean healthcare professionals and expansion of national health insurance to include these procedures.
Cysteine Biosynthesis Controls Serratia marcescens Phospholipase Activity

ABSTRACT Serratia marcescens causes health care-associated opportunistic infections that can be difficult to treat due to a high incidence of antibiotic resistance. One of the many secreted proteins of S. marcescens is the PhlA phospholipase enzyme. Genes involved in the production and secretion of PhlA were identified by screening a transposon insertion library for phospholipase-deficient mutants on phosphatidylcholine-containing medium. Mutations were identified in four genes (cyaA, crp, fliJ, and fliP) that are involved in the flagellum-dependent PhlA secretion pathway. An additional phospholipase-deficient isolate harbored a transposon insertion in the cysE gene encoding a predicted serine O-acetyltransferase required for cysteine biosynthesis. The cysE requirement for extracellular phospholipase activity was confirmed using a fluorogenic phospholipase substrate. Phospholipase activity was restored to the cysE mutant by the addition of exogenous l-cysteine or O-acetylserine to the culture medium and by genetic complementation. Additionally, phlA transcript levels were decreased 6-fold in bacteria lacking cysE and were restored with added cysteine, indicating a role for cysteine-dependent transcriptional regulation of S. marcescens phospholipase activity. S. marcescenscysE mutants also exhibited a defect in swarming motility that was correlated with reduced levels of flhD and fliA flagellar regulator gene transcription. Together, these findings suggest a model in which cysteine is required for the regulation of both extracellular phospholipase activity and surface motility in S. marcescens. IMPORTANCE Serratia marcescens is known to secrete multiple extracellular enzymes, but PhlA is unusual in that this protein is thought to be exported by the flagellar transport apparatus. In this study, we demonstrate that both extracellular phospholipase activity and flagellar function are dependent on the cysteine biosynthesis pathway. Furthermore, a disruption of cysteine biosynthesis results in decreased phlA and flagellar gene transcription, which can be restored by supplying bacteria with exogenous cysteine. These results identify a previously unrecognized role for CysE and cysteine in the secretion of S. marcescens phospholipase and in bacterial motility.
Evaluation of Health Plan Interventions to Influence Chronic Opioid Therapy Prescribing

Objectives:Evaluate health plan interventions targeting physician chronic opioid therapy (COT) prescribing. Materials and Methods:In 2006, Group Health’s (GH) Integrated Group Practice (IGP) initiated diverse interventions targeting COT prescriber norms and practices. In 2010, the IGP implemented a COT guideline, including a mandated online course for physicians managing COT. These interventions were not implemented in GH’s network practices. We compared trends in GH-IGP and network practices for 2006 to 2012 in the percent of patients receiving COT and their opioid dose. We compared physician beliefs before versus after the mandated course and precourse to postcourse changes in COT dosing for IGP physicians who took the course. Results:From 2006 to 2012, mean (SE) daily opioid dose among IGP COT patients (intervention setting) declined from 74.1 mg (1.9 mg) morphine equivalent dose (MED) to 48.3 mg (1.0 mg) MED. Dose changes among GH network COT patients (control setting) were modest—88.2 mg (5.0 mg) MED in 2006 to 75.7 mg (2.3 mg) MED in 2012. Among physicians taking the mandated course in 2011, we observed precourse to postcourse changes toward more conservative opioid prescribing beliefs. However, COT dosing trends did not change precourse to postcourse. Discussion:Following initiatives implemented to alter physician prescribing practices and norms, mean opioid dose prescribed to COT patients declined more in intervention than control practices. Physicians reported more conservative beliefs regarding opioid prescribing immediately after completing an online course in 2011, but the course was not associated with additional reductions in mean daily opioid dose prescribed by physicians completing the course.
The Interaction Between Schema Matching and Record Matching in Data Integration (Extended Abstract)

Schema Matching (SM) and Record Matching (RM) are two necessary steps in integrating multiple relational tables of different schemas, where SM unifies the schemas and RM detects records referring to the same real-world entity. The two processes have been thoroughly studied separately, but few attention has been paid to the interaction of SM and RM. In this work we find that, even alternating them in a simple manner, SM and RM can benefit from each other to reach a better integration performance (i.e., in terms of precision and recall). Therefore, combining SM and RM is a promising solution for improving data integration.