Miracle-dz/UniFAR-FTUs huggingface dataset:
The Weight‐of‐Evidence Approach and the Need for Greater International Acceptance of Its Use in Tackling Questions of Chemical Harm to the Environment

As we attempt to manage chemicals in the environment we need to be sure that our research efforts are being directed at the substances of greatest threat. All too often we focus on a chemical of concern and then cast around for evidence of its effects in an unstructured way. Risk assessment based on laboratory ecotoxicity studies, combined with field chemical measurements, can only take us so far. Uncertainty about the range and sufficiency of evidence required to take restorative action often puts policymakers in a difficult situation. We review this conundrum and reflect on how the “Hill criteria,” used widely by epidemiologists, have been applied to a weight‐of‐evidence approach (a term sometimes used interchangeably with ecoepidemiology) to build a case for causation. While using a set of such criteria to address sites of local environmental distress has been embraced by the US Environmental Protection Agency, we urge a wider adoption of weight‐of‐evidence approaches by policymakers, regulators, and scientists worldwide. A simplified series of criteria is offered. Progress will require a sustained commitment to long‐term wildlife and chemical monitoring over a sufficient geographic spread. Development of a comprehensive monitoring network, coupled with assembling evidence of harm in a structured manner, should be the foundation for protecting our ecosystems and human health. This will enable us to not only judge the success or failure of our efforts but also diagnose underlying causes. Environ Toxicol Chem 2021;40:2968–2977. © 2021 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Gaming, substance use and distress within a cohort of online gamblers.

BACKGROUND The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) included Internet Gaming Disorder (IGD) as a tentative diagnosis and inquires for additional research. The research on gaming is inconsistent regarding measurement approach and diagnostic cut-offs. Some scholars suggest the core approach, accentuating some of the diagnostic criteria to avoid pathologizing harmless behavior. Also, the co-occurrence of gaming and other addictions, gambling in specifically, is frequently reported but poorly understood. The present study aimed to explore gaming within a population of online gamblers in order to evaluate the core approach but also to investigate the possible co-occurrence of different addictions. DESIGN AND METHODS The present study is derived from material collected for a study on online gambling. The study addressed 1007 adult individuals from the general population who had gambled for money on an online casino site or an online betting site, on at least 10 occasions during the past 12 months. RESULTS Both the level of distress and problem gambling increased as the severity of gaming increased. The co-occurrence of problems with alcohol, illicit drug use/prescription sedatives/strong painkillers and gambling was roughly 50% among the addictive gamers. CONCLUSION The present study suggests that the core approach manages to distinguish in severity of gaming in regards to interference and comorbidity. We also brought light to the occurrence of gaming within a population of gamblers and our results indicate that this specific group of addicted gamers are particularly burdened by co-occurrent addictive behaviors and severe distress.
Development of college student focused care in a psychiatric hospital: Preliminary clinical outcomes and future directions

Abstract Objective The unique features of college experience make it essential to address escalating mental-health challenges beyond college campuses. In 2010, we launched college-student focused (CSF) care nested within an adult day treatment program in a psychiatric hospital. The CSF care consists of student group therapies, individual consultation services for hospital staff and student-patients, and student-focused mental health guides for patients and families. This study preliminarily examined the clinical impact of CSF care on post-treatment symptoms reduction. Participants and Methods In 235 college student-patients admitted to the day program between 2011 July to 2013 January, we assessed the targeted outcomes of the CSF care, using a newly developed CSF questionnaire. Results Higher levels of CSF care-related outcomes predicted reduced post-treatment depression and anxiety, even after controlling for baseline clinical symptoms and post-treatment skills usage. Conclusions These results highlighted the benefits and need for CSF care on a healthcare system level.
Noncanonical Wnt Signaling in the Integrity of the Blood-Testis Barrier and Sperm Release

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercialNoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com © The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. Commentary
Polycomb Repressive Complex 2 Modulation through the Development of EZH2–EED Interaction Inhibitors and EED Binders

Epigenetics is nowadays a well-accepted area of research. In the last years, tremendous progress was made regarding molecules targeting EZH2, directly or indirectly. Recently tazemetostat hit the market after FDA-approval for the treatment of lymphoma. However, the impairment of EZH2 activity by orthosteric intervention has proven to be effective only in a limited subset of cancers. Considering the multiproteic nature of the PRC2 complex and the marked dependence of EZH2 functions on the other core subunits such as EED, in recent years, a new targeting approach ascended to prominence. The possibility to cripple the function of the PRC2 complex by interfering with its multimeric integrity fueled the interest in developing EZH2–EED protein–protein interaction and EED inhibitors as indirect modulators of PRC2-dependent methyltransferase activity. In this Perspective, we aim to summarize the latest findings regarding the development and the biological activity of these emerging classes of PRC2 modulators from a medicinal chemist’s viewpoint.
Borophene as Efficient Sulfur Hosts for Lithium–Sulfur Batteries: Suppressing Shuttle Effect and Improving Conductivity

Stabilizing polysulfide shuttle while ensuring high sulfur loading holds the key to realizing high energy density of lithium–sulfur (Li–S) batteries. Herein we present our first-principles calculation on borophene as host of cathode in Li–S battery. The adsorption energies of sulfur cluster (S8) and its discharge products (Li2S8, Li2S6, Li2S4, Li2S2, and Li2S) on borophene are calculated. Our results indicate that borophene host can trap lithium polysulfides stably and effectively, which could avoid shuttle effect and improve the utilization of active material. The band structure of the adsorption structures shows that the borophene–sulfur cluster is metallic, while partial charge density proves that the conductivity is mainly due to the metallic borophene substrate. Such favorable electrical conductivity is helpful to the cathode charge/discharge processes. Therefore, borophene could be a promising host for S cathode due to its strong adsorption, high conductivity, and small deformation.
The RNA‐binding protein and stress granule component ATAXIN‐2 is expressed in mouse and human tissues associated with glaucoma pathogenesis

Polyglutamine repeat expansions in the Ataxin‐2 (ATXN2) gene were first implicated in Spinocerebellar Ataxia Type 2, a disease associated with degeneration of motor neurons and Purkinje cells. Recent studies linked single nucleotide polymorphisms in the gene to elevated intraocular pressure in primary open angle glaucoma (POAG); yet, the localization of ATXN2 across glaucoma‐relevant tissues of the vertebrate eye has not been thoroughly examined. This study characterizes ATXN2 expression in the mouse and human retina, and anterior eye, using an antibody validated in ATXN2−/− retinas. ATXN2‐ir was localized to cytosolic sub compartments in retinal ganglion cell (RGC) somata and proximal dendrites in addition to GABAergic, glycinergic, and cholinergic amacrine cells in the inner plexiform layer (IPL) and displaced amacrine cells. Human, but not mouse retinas showed modest immunolabeling of bipolar cells. ATXN2 immunofluorescence was prominent in the trabecular meshwork and pigmented and nonpigmented cells of the ciliary body, with analyses of primary human trabecular meshwork cells confirming the finding. The expression of ATXN2 in key POAG‐relevant ocular tissues supports the potential role in autophagy and stress granule formation in response to ocular hypertension.
In vivo typing of Escherichia coli obtained from laying chickens with the E. coli peritonitis syndrome

ABSTRACT Fourteen genetically different chicken Escherichia coli strains were biotyped in hens to examine if any E. coli strain at high dose can induce the E. coli peritonitis syndrome (EPS). Moreover, biotyping was performed in embryos and the median lethal dose (LD50) of three strains was determined in hens. Nine strains were obtained from femur marrow and one strain from caecum of hens that had died from EPS. One strain originated from the inflamed pericardium of a broiler and three strains from the cloaca of specified pathogen-free (SPF) broiler breeders. Strains were inoculated intratracheally into separate groups of 32 productive SPF White Leghorn (WL) hens at a dose of 7.8–9.2 log10 colony forming units (CFU) per hen and into the allantoic cavity of separate groups of 20 SPF WL embryos incubated during 14 days in a dose of 4.2–4.6 log10 CFU per embryo. The embryo test was replicated. Bone marrow and pericardium strains induced EPS, the other strains did not. Based on mortality in hens, EPS-inducing strains could be classified as very virulent (59–100% mortality), moderately virulent (38% mortality) and low virulent (6% mortality). In productive SPF WL hens, the LD50 of three very virulent strains ranged from <2.7 to 5.3 log10 CFU. Virulent and avirulent strains killed 60–95% and 0–30% of embryos, respectively. The embryo lethality test, which showed good reproducibility, did not discriminate within virulent strains, but can nevertheless be considered as a useful alternative for biotyping E. coli in productive hens. RESEARCH HIGHLIGHTS Even at high doses, not all E. coli strains can induce EPS. Substantial differences in virulence exist within very virulent E. coli strains. The embryo lethality test is a useful alternative for biotyping E. coli in laying hens. Broiler colibacillosis may represent a source of EPS strains for layers and vice versa.
Draft Genome Sequences of Clinical Respiratory Isolates of Mycobacterium goodii Recovered in Ireland

Here, we describe the draft genomes of five Mycobacterium goodii isolates that were recovered from respiratory clinical specimens in Ireland. Currently, one complete genome and one draft genome exist publicly for M. goodii. ABSTRACT Here, we describe the draft genomes of five Mycobacterium goodii isolates that were recovered from respiratory clinical specimens in Ireland. Currently, one complete genome and one draft genome exist publicly for M. goodii.
Comparison of predictive value of risk scores for gastrointestinal bleeding in antiplatelet therapy

Abstract Gastrointestinal bleeding (GIB) is the most common serious bleeding complication of antiplatelet therapy. The bleeding risk score (BRS) of GIB may help to determine the risk of bleeding, and provides a reference for the formulation of antiplatelet therapy regimen in clinical practice, but we found that no specific risk scores are available in East Asian patients. This study analyzed patients who were administered antiplatelet therapy from May 2015 to December 2018 in two medical centers. Patient’s baseline data were obtained. We assessed four BRSs (New Score, RIETE Score, Cuschieri Score, de Groot Score) and compared them using the area under the receiver operating characteristic curve (AUC). The 4,052 patients enrolled in this study had an average age of 69.6 ± 10.8 years, and 65.9% of them were male. Among the 4,052 patients included, 171 patients experienced GIB within 6 months of follow-up. In the study population, the AUCs for the New, RIETE, Cuschieri, and de Groot scores were 0.673 (95% confidence interval (CI) 0.616–0.729, P < . 001), 0.742 (95% CI 0.690–0.794, P < .001), 0.598 (95% CI 0.537–0.659, P = .002), and 0.875 (95% CI 0.839–0.912, P < .001), respectively. After validation, the de Groot Score has better performance. Among the four scores, the de Groot Score might be more suitable for helping Chinese clinicians to predict the risk of GIB in patients taking antiplatelet drugs, and reduce GIB events.
Mastocytosis and melanoma: a case series

Mayo Clinic Alix School of Medicine, Scottsdale, AZ, USA, Department of Dermatology, Mayo Clinic, Rochester, MN, USA, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA, Division of Medical Oncology, Department of Oncology, Mayo Clinic, Rochester, MN, USA, Department of Immunology, Mayo Clinic, Rochester, MN, USA, Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA, and Department of Pediatrics, Mayo Clinic, Rochester, MN, USA
Advances in Diagnostic and Interventional Radiology in Hepatocellular Carcinoma

Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths, and radiological imaging and locoregional therapies are essential for the management of patients with HCC. Summary: In cirrhotic patients, a characteristic imaging pattern establishes the noninvasive diagnosis of HCC with acceptable sensitivity and high specificity. In addition to diagnosis, imaging is used in the staging of patients and treatment allocation. Multiparametric MRI with hepatospecific contrast agents improves lesion detection, characterization, and treatment allocation; recently described imaging criteria allow identification of precursor lesions. Radiofrequency ablation (RFA) and transarterial chemoembolization (TACE) have been established in the treatment of patients with HCC at the early and intermediate stages, respectively. Microwave ablation has been described as an alternative to RFA in selected cases. Imaging-guided brachytherapy, a catheter-based radiotherapy technique, offers advantages to overcome some limitations of the aforementioned therapies, including the tumor location and size. Currently, no adjuvant therapy is recommended after RFA or TACE, but several new drugs are under evaluation. Furthermore, although the exact role of selective internal radiation therapy (SIRT) in HCC still needs to be defined, it is an alternative to systemic agents in patients with intolerance, and additional benefit has been shown in selected subgroups. Additionally, SIRT offers an alternate to TACE with higher objective response rates in patients who needs bridging before transplantation. Key Messages: New imaging criteria improved lesion detection in patients at a risk for HCC, and advances in interventional therapies expanded the range of patients eligible for locoregional treatments.
Electronic Cigarette Cessation among Adolescents and Young Adults

Abstract Background E-cigarette use is common among adolescents and young adults, yet little is known about e-cigarette cessation among this group. The current study assessed e-cigarette cessation attempts, interest in e-cigarette cessation, and methods of e-cigarette cessation most favored by young e-cigarette users. Methods A cross-sectional survey was administered via Facebook and Instagram between February and April 2019 to enroll current, regular e-cigarette using adolescents and young adults who reported non-regular use of other tobacco products. Participants included 212 (51.4% female) adolescents and young adults (14 to 21 years of age) who reported six or more days of e-cigarette use and less than four days of other tobacco product use in the last 30 days. Results More than half (n = 110; 51.9%) of the participants reported at least one past serious e-cigarette quit attempt. Among those, the average number of past quit attempts was 2.9 (SD = 3.9). Of the 157 (74.1%) participants who indicated they were interested in quitting e-cigarettes, 78 (49.7%) endorsed health risks as their primary reason for wanting to quit e-cigarettes. The most frequently endorsed intervention methods to aid in e-cigarette cessation were those delivered via digital methods, such as smartphone apps. Conclusion The current study provides preliminary data to support continued development of e-cigarette cessation treatments for adolescents and young adults. Future research should evaluate the potential use of digital methods to aid in e-cigarette cessation.
Protective effect of soluble Klotho in pediatric patients undergoing cardiac surgery with cardiopulmonary bypass support—A pilot study

The Klotho protein family plays important roles in several metabolic pathways. Soluble Klotho has been recently put forward as an antiaging protein, demonstrating renal and cardiovascular protective traits. Cardiopulmonary bypass (CPB) support during cardiac surgery has been implicated in several adverse outcomes in pediatric and adult patients. Our goal was to assess whether serum Klotho levels can be used to predict outcomes in children undergoing cardiac surgery with CPB due to congenital heart defects (CHDs).
In situ Chromatin Interaction Analysis Using Paired‐End Tag Sequencing

Chromatin Interaction Analysis Using Paired‐End Tag Sequencing (ChIA‐PET) is an established method to map protein‐mediated chromatin interactions. A limitation, however, is that it requires a hundred million cells per experiment, which hampers its broad application in biomedical research, particularly in studies in which it is impractical to obtain a large number of cells from rare samples. To reduce the required input cell number while retaining high data quality, we developed an in situ ChIA‐PET protocol, which requires as few as 1 million cells. Here, we describe detailed step‐by‐step procedures for performing in situ ChIA‐PET from cultured cells, including both an experimental protocol for sample preparation and data generation and a computational protocol for data processing and visualization using the ChIA‐PIPE pipeline. As the protocol significantly simplifies the experimental procedure, reduces ligation noise, and decreases the required input of cells compared to previous versions of ChIA‐PET protocols, it can be applied to generate high‐resolution chromatin contact maps mediated by various protein factors for a wide range of human and mouse primary cells. © 2021 The Authors. Current Protocols published by Wiley Periodicals LLC.
The AMP‐dependent kinase pathway is upregulated in BAP1 mutant uveal melanoma

Metastatic uveal melanoma (UM) responds poorly to targeted therapies and immune checkpoint inhibitors. Loss of BRCA1‐associated protein 1 (BAP1) via inactivating mutations in the BAP1 gene is associated with UM progression. Thus, molecular alterations caused by BAP1 dysfunction may be novel therapeutic targets for metastatic UM. Here, we found that phosphorylation of AMP‐dependent kinase (AMPK) was elevated in BAP1‐altered (or mutant) compared to BAP1‐unaltered (or wild‐type [WT]) UM tumors. As a readout of AMPK pathway activation, phosphorylation of an AMPK downstream effector, acetyl‐CoA‐carboxylase (ACC), was also elevated. BAP1 re‐expression in BAP1‐null UM cell lines decreased phospho‐AMPK (pAMPK) and phospho‐ACC (pACC) levels. AMPK phosphorylation is mediated by calcium/calmodulin dependent protein kinase kinase 2 (CaMKK2) and potentially liver kinase B1 (LKB1) in BAP1 mutant UM cells. Knockdown of AMPKα1/2 reduced the viability of BAP1 mutant UM cells, indicating a survival function of AMPK in BAP1 mutant UM. Our data suggest that the AMPK pathway is an important mechanism mediating the survival of BAP1 mutant UM. Targeting the AMPK pathway may be a novel therapeutic strategy for metastatic UM.
Biased orientation representations can be explained by experience with nonuniform training set statistics

Visual acuity is better for vertical and horizontal compared to other orientations. This cross-species phenomenon is often explained by “efficient coding”, whereby more neurons show sharper tuning for the orientations most common in natural vision. However, it is unclear if experience alone can account for such biases. Here, we measured orientation representations in a convolutional neural network, VGG-16, trained on modified versions of ImageNet (rotated by 0°, 22.5°, or 45° counter-clockwise of upright). Discriminability for each model was highest near the orientations that were most common in the network’s training set. Furthermore, there was an over-representation of narrowly tuned units selective for the most common orientations. These effects emerged in middle layers and increased with depth in the network. Our results suggest that biased orientation representations can emerge through experience with a non-uniform distribution of orientations, supporting the efficient coding hypothesis. Author Summary Observers tend to have more precise vision for items that are oriented vertically or horizontally compared to items oriented diagonally. This perceptual bias may be an adaptation to the statistics of the visual environment, where items such as trees, buildings, and the horizon naturally create horizontal and vertical edges. Here, we tested this hypothesis by taking a popular computational model of the visual system (a convolutional neural network, or CNN), and training it to perform object recognition on images that were either upright or rotated. Measuring orientation representations in the trained model revealed that orientation discriminability was highest near whichever orientations were most common in the training image set, and more neural network units showed a preference for those orientations. These results support the hypothesis that orientation biases reflect an adaptation to environmental statistics.
A domain damage index to prioritizing the pathogenicity of missense variants

Prioritizing causal variants is one major challenge for the clinical application of sequencing data. Prompted by the observation that 74.3% of missense pathogenic variants locate in protein domains, we developed an approach named domain damage index (DDI). DDI identifies protein domains depleted of rare missense variations in the general population, which can be further used as a metric to prioritize variants. DDI is significantly correlated with phylogenetic conservation, variant‐level metrics, and reported pathogenicity. DDI achieved great performance for distinguishing pathogenic variants from benign ones in three benchmark datasets. The combination of DDI with the other two best approaches improved the performance of each individual method considerably, suggesting DDI provides a powerful and complementary way of variant prioritization.