Miracle-dz/UniFAR-FTUs huggingface dataset:
Eomesodermin promotes the development of type 1 regulatory T (TR1) cells

TR1 cells are the major regulatory population generated after allogeneic bone marrow transplantation. Regulatory T cells sans FoxP3 Although expression of FoxP3 is largely synonymous with regulatory T (Treg) cell identity in mice, type 1 regulatory T (TR1) cells are an exception. TR1 cells produce interleukin-10 but are FoxP3−. In comparison with FoxP3+ Treg cells, the development and functions of TR1 cells are poorly understood. Here, Zhang et al. report that TR1 cells play a critical regulatory role after allogeneic bone marrow transplantation (BMT) in mice and use this model to delineate the molecular circuits driving commitment to the TR1 cell lineage. By documenting the presence of TR1 cells after BMT in humans, they propose that modulation of TR1 cells could be a therapeutic venue for increasing BMT success rates in the clinic. Type 1 regulatory T (TR1) cells are Foxp3− interleukin-10 (IL-10)–producing CD4+ T cells with potent immunosuppressive properties, but their requirements for lineage development have remained elusive. We show that TR1 cells constitute the most abundant regulatory population after allogeneic bone marrow transplantation (BMT), express the transcription factor Eomesodermin (Eomes), and are critical for the prevention of graft-versus-host disease. We demonstrate that Eomes is required for TR1 cell differentiation, during which it acts in concert with the transcription factor B lymphocyte–induced maturation protein-1 (Blimp-1) by transcriptionally activating IL-10 expression and repressing differentiation into other T helper cell lineages. We further show that Eomes induction in TR1 cells requires T-bet and donor macrophage–derived IL-27. Thus, we define the cellular and transcriptional control of TR1 cell differentiation during BMT, opening new avenues to therapeutic manipulation.
Statistical Power for Trend-in-trend Design.

© 2018 Wolters Kluwer Health, Inc. All rights reserved. www.epidem. com | e21 expectations and probabilities yielded the true decrease of 0.20. An anonymous reviewer noted that the derivation above also holds with certain additional edges in the causal diagram, such as W Y → or A S → . These would lead to, respectively, edges W A Y a ( ) → ( ) or a S a → ( ) in the single-world intervention graph. In the latter case, S a ( ) is d-separated from Y a ( ) given W a ( ) and a , thus S a ( ) would remain independent of Y a ( ) conditional on W a ( ) (Theorem 12 in Richardson and Robins3). The reviewer also noted that the derivation fails with unmeasured confounding between A and W or between S and Y .
Kaposi sarcoma herpesvirus pathogenesis

Kaposi sarcoma herpesvirus (KSHV), taxonomical name human gammaherpesvirus 8, is a phylogenetically old human virus that co-evolved with human populations, but is now only common (seroprevalence greater than 10%) in sub-Saharan Africa, around the Mediterranean Sea, parts of South America and in a few ethnic communities. KSHV causes three human malignancies, Kaposi sarcoma, primary effusion lymphoma, and many cases of the plasmablastic form of multicentric Castleman's disease (MCD) as well as occasional cases of plasmablastic lymphoma arising from MCD; it has also been linked to rare cases of bone marrow failure and hepatitis. As it has colonized humans physiologically for many thousand years, cofactors are needed to allow it to unfold its pathogenic potential. In most cases, these include immune defects of genetic, iatrogenic or infectious origin, and inflammation appears to play an important role in disease development. Our much improved understanding of its life cycle and its role in pathogenesis should now allow us to develop new therapeutic strategies directed against key viral proteins or intracellular pathways that are crucial for virus replication or persistence. Likewise, its limited (for a herpesvirus) distribution and transmission should offer an opportunity for the development and use of a vaccine to prevent transmission. This article is part of the themed issue ‘Human oncogenic viruses’.
Dockerface: an easy to install and use Faster R-CNN face detector in a Docker container

Face detection is a very important task and a necessary pre-processing step for many applications such as facial landmark detection, pose estimation, sentiment analysis and face recognition. Not only is face detection an important pre-processing step in computer vision applications but also in computational psychology, behavioral imaging and other fields where researchers might not be initiated in computer vision frameworks and state-of-the-art detection applications. A large part of existing research that includes face detection as a pre-processing step uses existing out-of-the-box detectors such as the HoG-based dlib and the OpenCV Haar face detector which are no longer state-of-the-art - they are primarily used because of their ease of use and accessibility. We introduce Dockerface, a very accurate Faster R-CNN face detector in a Docker container which requires no training and is easy to install and use.
A Comprehensive Study of Costs Associated With Recurrent Clostridium difficile Infection

BACKGROUND Clostridium difficile infection (CDI) is the most common healthcare-associated infection and is associated with considerable morbidity. Recurrent CDI is a key contributing factor to this morbidity. Despite an estimated 83,000 recurrences annually in the United States, there are few accurate estimates of costs associated with recurrent CDI. OBJECTIVE We performed this study (1) to identify the health consequences of recurrent CDI including need for repeat hospitalization, intensive care unit (ICU) stay, and surgery; (2) to determine costs associated with recurrent CDI and identify determinants of such costs; and (3) to compare the outcomes and costs of recurrent CDI to those who develop reinfection. METHODS We identified all patients with confirmed recurrent CDI between January to December 2013 at a single referral center. Healthcare burden associated with recurrence including diagnostic testing, pharmacologic treatment, and inpatient and outpatient healthcare visits were identified in the 12 months following the first recurrence. Total healthcare costs were calculated, and the predictors of high healthcare utilization were identified. RESULTS Our study population included 98 patients with recurrent CDI. The median interval between the initial infection and recurrence was 37 days. The mean age of the cohort was 67 years, two-thirds were women (62%), and the mean Charlson index was 8.6. During the year following the first recurrence of CDI, each patient underwent a mean of 4.4 stool C. difficile toxin tests and received a mean of 2.5 prescriptions for oral vancomycin (range, 0–6). Most patients (84%) with recurrence had a CDI-related hospitalization, and 6% underwent colectomy. The mean total CDI-associated cost was $34,104 per patient, with hospitalization costs accounting for 68%, surgery 20%, and drug treatment 8% of this cost, respectively. Extrapolating to the United States overall, we estimate an annual cost of $2.8 billion related to recurrent CDI. CONCLUSION Recurrent CDI is associated with considerable morbidity and cost. Infect Control Hosp Epidemiol 2017;38:196–202
Influence of Wear Performance of PTA Processed High Speed Steel Hardfacing by Solidification Kinetics

Fe-based hardfacings with high vanadium content become more important for industrial applications because of low production and material costs, combined with high abrasion resistance. The aim of this work is to gain a deeper fundamental understanding of heat management impact of a Fe-based hardfacing alloy on resulting wear properties related to real field conditions. In this work a FeVCrC alloy was deposited by plasma transferred arc welding technology varying solidification kinetics due to active heat management. In-situ thermal couple measurements during processing were performed to determine t8/5 cooling-off time relevant for precipitation formation. Microstructural investigation was done by microscopy (e.g. OM, SEM), X-ray diffraction as well as macroscopic hardness, respectively. Wear performance was characterized by using the ASTM G65 dry-sand rubber-wheel procedure A for 3-body abrasion under low-stress. In addition 2-body impact/abrasion behavior was evaluated utilizing continuous impact abrasion test (CIAT). For quantitative wear description 3D microscopy and mass loss determination were done after the test. Additional SEM investigations on the worn surface and on the tribologically stressed near-surface region were applied to deepen the fundamental wear understanding.Results showed that the t8/5 cooling-off time is strongly influenced by solidification conditions due to thermal substrate properties. Nevertheless t8/5 cooling-off time is not necessarily correlated to wear behavior. Significant variations of micro-and macro structural parameters were obtained for dilution with substrate, precipitation content and distribution, whereas macro hardness was obtained on a relatively constant level. Two-body impact/abrasion wear behavior showed plastically deformed zones where the fine precipitations act in a ductile way. Under 3-body abrasion conditions precipitations of hard phases play a dominant role for providing high wear resistance related to microstructural features like amount, distribution and size of precipitations. It can be claimed that no direct correlation of 2-body and 3-body wear rates with deposition hardness of hardfacing has been observed.
An Examination of HPV16 Natural Immunity in Men Who Have Sex with Men (MSM) in the HPV in Men (HIM) Study

Background: Evidence suggests that natural antibodies developed after HPV16 infection may protect some women but not men against subsequent HPV16 reacquisition. Less is known whether antibodies developed following HPV16 infection are protective among men who have sex with men (MSM). Methods: Four hundred seventy-five MSM from the Human Papillomavirus Infection in Men (HIM) study were tested for serum antibodies to HPV16 L1 using enzyme-linked immunosorbent assays, and for anal and genital HPV16 DNA using PCR consensus primer system (PGMY 09/11). Adjusted Cox regression was used to evaluate whether baseline HPV16 seropositivity impacts subsequent genital or anal HPV16 DNA. Results: The risk of subsequent genital HPV16 [aHR = 1.05, 95% confidence interval (CI) = 0.66–1.68] and anal HPV16 infections among MSM (aHR = 2.34, 95% CI = 0.92–5.98) was similar or nonsignificantly higher in HPV16-seropositive than HPV16-seronegative MSM. The risk of genital HPV16 was also similar between HPV16-seronegative and HPV16-seropositive MSM in the highest tertile of HPV16 antibody levels and when restricting to those with new sex partners during follow-up (P > 0.20). Among the 118 MSM who were HPV16 seropositive, 90% remained HPV16 seropositive up to 4 years later. When tested together, MSM with the highest antibody titers (top tertile) had similar levels to females (mean = 130.3 vs. 134.5 EU/mL, P = 0.84). Conclusions: Despite years of HPV16 seropositivity persistence and antibody titers comparable with females, this study suggested no evidence of HPV16 natural antibodies protecting against subsequent genital or anal HPV16 infection in MSM. Impact: This could help partially explain the high incidence of genital and anal HPV16 infection and related anal cancer seen in middle-aged and older MSM. Cancer Epidemiol Biomarkers Prev; 27(4); 496–502. ©2018 AACR.
Accurate determination of electronic transport properties of semiconductor wafers with spatially resolved photo-carrier techniques

Spatially resolved photo-carrier techniques, in which a modulated and tightly focused laser beam with photon energy larger than the band gap of the semiconductor material under investigation is employed to generate free carriers, are applied to the simultaneous determination of the electronic transport properties of semiconductor wafers, that is, the carrier lifetime, the carrier diffusivity, and the front surface recombination velocity. The simultaneous determination is fulfilled by measuring and multi-parameter fitting the modulation-frequency-dependent three-dimensional distribution of photo-generated free carriers in a semiconductor wafer to a rigorous three-dimensional theoretical model. The uncertainties of the fitted parameter values are analyzed by investigating the dependence of a mean square variance including both amplitude and phase errors on the corresponding transport parameters and compared to that obtained by the conventional frequency-scan approach, in which only the frequency dependence of the amplitude and phase of the photo-carrier signals are recorded at the excitation spot. Both theoretical simulations and experimental results show that the accuracy of the simultaneous multi-parameter determination is greatly improved by the spatially resolved information of the photo-generated free-carrier diffusion in the semiconductor wafers.
Predicting negative emotional states following first onset acute coronary syndrome

This study identified predictors of anxiety and depression in patients with acute coronary syndrome. Predictors included illness beliefs, fear/threat at the time of the cardiac event, threat reappraisal over time and social support. A total of 97 participants completed questionnaires in hospital and 1- and 6-month follow-up. Perceived threat and fear at the time of the cardiac event predicted affective response at both time points, partly mediated by threat reappraisal. Contemporaneous measures of illness beliefs contributed additional variance, although not always in the predicted direction: high concern and control over the illness were associated with emotional distress. Assessment of patients for risk of negative emotional outcomes of acute coronary syndrome needs to consider their beliefs about their illness and the degree of threat and fear experienced at the time of the event. Interventions need to help people cope with negative emotional states as well as challenging inappropriate illness beliefs.
Dementia incidence and predictors in cerebral amyloid angiopathy patients without intracerebral hemorrhage

Cerebral amyloid angiopathy (CAA) is a common cause of cognitive impairment in older individuals. This study aimed to investigate predictors of dementia in CAA patients without intracerebral hemorrhage (ICH). A total of 158 non-demented patients from the Stroke Service or the Memory Clinic who met the modified Boston Criteria for probable CAA were included. At baseline, neuroimaging markers, including lobar microbleeds (cerebral microbleeds (CMBs)), white matter hyperintensities (WMH), cortical superficial siderosis (cSS), magnetic resonance imaging (MRI)-visible centrum semiovale perivascular spaces (CSO-PVS), lacunes, and medial temporal atrophy (MTA) were assessed. The overall burden of small vessel disease (SVD) for CAA was calculated by a cumulative score based on CMB number, WMH severity, cSS presence and extent and CSO-PVS severity. The estimated cumulative dementia incidence at 1 year was 14% (95% confidence interval (CI): 5%–23%), and 5 years 73% (95% CI: 55%, 84%). Age (hazard ratio (HR) 1.05 per year, 95% CI: 1.01–1.08, p = 0.007), presence of MCI status (HR 3.40, 95% CI: 1.97–6.92, p < 0.001), MTA (HR 1.71 per point, 95% CI: 1.26–2.32, p = 0.001), and SVD score (HR 1.23 per point, 95% CI: 1.20–1.48, p = 0.030) at baseline were independent predictors for dementia conversion in these patients. Cognitive deterioration of CAA patients appears attributable to cumulative changes, from both vasculopathic and neurodegenerative lesions.
The Fragile Spell of Desire: A Functional Perspective on Changes in Sexual Desire Across Relationship Development

The sexual behavioral system evolved to motivate reproductive acts by arousing sexual desire. Building on the idea that this system has also been “exploited” by evolutionary processes to promote enduring bonds between romantic partners, the present article introduces an integrative model that delineates the functional significance of sexual desire in relationship formation and maintenance. This model explains why individuals’ sexual reaction to their partner is context-dependent, clarifying how changes in the nature of interdependence over the course of relationships alter the ways in which specific predictors of sexual desire tend to promote (or inhibit) desire and thereby affect relationship depth and stability. The model postulates that although desire influences the development of attachment bonds, the contribution that it makes varies over the course of relationships. The model also provides new insight regarding fundamental but unresolved issues in human sexuality, such as the vulnerability of sexual desire and the desire-intimacy paradox.
Tanshinone-IIA attenuates the deleterious effects of oxidative stress in osteoporosis through the NF-κB signaling pathway

Osteoclasts are responsible for bone resorption caused by bone microstructural damage and bonerelated disorders. Evidence shows that tanshinone IIA (Tan-IIA), a traditional Chinese medicine, is used clinically as a drug for the treatment of cardiovascular and cerebrovascular diseases. However, the efficacy and mechanism underlying the effect of Tan-IIA on the viability of osteoclasts remain to be fully elucidated. The present study investigated the therapeutic effects of Tan-IIA on osteoblast differentiation and oxidative stress in vitro and in vivo. Cell viability was analyzed and oxidative stress was examined in the osteoblasts. Wnt1sw/sw mice were used to investigate the therapeutic effects of Tan-IIA on spontaneous tibia fractures and severe osteopenia. The bone strength, collagen and mineral were examined in the tibia. Osteoblast activity was also analyzed in the experimental mice. The Tan-IIA-induced differentiation of osteoclasts and the mechanism of action were investigated in osteocytes. The data showed that Tan-IIA treatment improved cell viability. The data also demonstrated that Tan-IIA decreased the levels of H2O2, accumulation of reactive oxygen species and apoptosis of osteoblasts. Tan-IIA inhibited the deleterious outcomes triggered by oxidative stress. In addition, Tan-IIA inhibited the activation of nuclear factor (NF)-κB and its target genes, tumor necrosis factor (TNF)-α, inducible nitric oxide synthase and cyclooxygenase 2, and increased the levels of TNF receptor-associated factor 1 and inhibitor of apoptosis protein-1/2 in the osteocytes. Furthermore, it was shown that Tan-IIA reduced the propensity to fractures and severe osteopenia in mice with osteoporosis. Tan-IIA also exhibited improved bone strength, mineral and collagen in the bone matrix of the experimental mice. It was found that the Tan-IIA-mediated benefits on osteoblast activity and function were through the NF-κB signaling pathway. Taken together, the data obtained in the present study suggested that Tan-IIA had protective effects against oxidative stress in osteoblastic differentiation in mice with osteoporosis by regulating the NF-κB signaling pathway.
Assessing the Impact of Copy Number Variants on miRNA Genes in Autism by Monte Carlo Simulation

Autism Spectrum Disorders (ASDs) are childhood neurodevelopmental disorders with complex genetic origins. Previous studies have investigated the role of de novo Copy Number Variants (CNVs) and microRNAs as important but distinct etiological factors in ASD. We developed a novel computational procedure to assess the potential pathogenic role of microRNA genes overlapping de novo CNVs in ASD patients. Here we show that for chromosomes # 1, 2 and 22 the actual number of miRNA loci affected by de novo CNVs in patients was found significantly higher than that estimated by Monte Carlo simulation of random CNV events. Out of 24 miRNA genes over-represented in CNVs from these three chromosomes only hsa-mir-4436b-1 and hsa-mir-4436b-2 have not been detected in CNVs from non-autistic subjects as reported in the Database of Genomic Variants. Altogether the results reported in this study represent a first step towards a full understanding of how a dysregulated expression of the 24 miRNAs genes affect neurodevelopment in autism. We also propose that the procedure used in this study can be effectively applied to CNVs/miRNA genes association data in other genomic disorders beyond autism.
A Multivariate Model of Stakeholder Preference for Lethal Cat Management

Identifying stakeholder beliefs and attitudes is critical for resolving management conflicts. Debate over outdoor cat management is often described as a conflict between two groups, environmental advocates and animal welfare advocates, but little is known about the variables predicting differences among these critical stakeholder groups. We administered a mail survey to randomly selected stakeholders representing both of these groups (n = 1,596) in Florida, where contention over the management of outdoor cats has been widespread. We used a structural equation model to evaluate stakeholder intention to support non-lethal management. The cognitive hierarchy model predicted that values influenced beliefs, which predicted general and specific attitudes, which in turn, influenced behavioral intentions. We posited that specific attitudes would mediate the effect of general attitudes, beliefs, and values on management support. Model fit statistics suggested that the final model fit the data well (CFI = 0.94, RMSEA = 0.062). The final model explained 74% of the variance in management support, and positive attitudes toward lethal management (humaneness) had the largest direct effect on management support. Specific attitudes toward lethal management and general attitudes toward outdoor cats mediated the relationship between positive (p<0.05) and negative cat-related impact beliefs (p<0.05) and support for management. These results supported the specificity hypothesis and the use of the cognitive hierarchy to assess stakeholder intention to support non-lethal cat management. Our findings suggest that stakeholders can simultaneously perceive both positive and negative beliefs about outdoor cats, which influence attitudes toward and support for non-lethal management.
High-Quality NMR Structure of Human Anti-Apoptotic Protein Domain Mcl-1(171-327) for Cancer Drug Design

A high-quality NMR solution structure is presented for protein hMcl-1(171–327) which comprises residues 171–327 of the human anti-apoptotic protein Mcl-1 (hMcl-1). Since this construct contains the three Bcl-2 homology (BH) sequence motifs which participate in forming a binding site for inhibitors of hMcl-1, it is deemed to be crucial for structure-based design of novel anti-cancer drugs blocking the Mcl1 related anti-apoptotic pathway. While the coordinates of an NMR solution structure for a corresponding construct of the mouse homologue (mMcl-1) are publicly available, our structure is the first atomic resolution structure reported for the ‘apo form’ of the human protein. Comparison of the two structures reveals that hMcl-1(171–327) exhibits a somewhat wider ligand/inhibitor binding groove as well as a different charge distribution within the BH3 binding groove. These findings strongly suggest that the availability of the human structure is of critical importance to support future design of cancer drugs.