bluuebunny/crossref_metadata_2025_split huggingface dataset:
A descriptive analysis of 2020 California Occupational Safety and Health Administration COVID-19-related complaints
Authors: Thomas Marilyn D , Matthay Ellicott C. , Duchowny Kate A. , Riley Alicia R. , Khela Harmon , Chen Yea-Hung , Bibbins-Domingo Kirsten , Glymour M. Maria 
Published: December 2021

AbstractCOVID-19 mortality disproportionately affected specific occupations and industries. The Occupational Safety and Health Administration (OSHA) protects the health and safety of workers by setting and enforcing standards for working conditions. Workers may file OSHA complaints about unsafe conditions. Complaints may indicate poor workplace safety during the pandemic. We evaluated COVID-19-related complaints filed with California (Cal)/OSHA between January 1, 2020 and December 14, 2020 across seven industries. To assess whether workers in occupations with high COVID-19-related mortality were also most likely to file Cal/OSHA complaints, we compared industry-specific per-capita COVID-19 confirmed deaths from the California Department of Public Health with COVID-19-related complaints. Although 7,820 COVID-19-related complaints were deemed valid by Cal/OSHA, only 627 onsite inspections occurred and 32 citations were issued. Agricultural workers had the highest per-capita COVID-19 death rates (402 per 100,000 workers) but were least represented among workplace complaints (44 per 100,000 workers). Health Care workers had the highest complaint rates (81 per 100,000 workers) but the second lowest COVID-19 death rate (81 per 100,000 workers). Industries with the highest inspection rates also had high COVID-19 mortality. Our findings suggest complaints are not proportional to COVID-19 risk. Instead, higher complaint rates may reflect worker groups with greater empowerment, resources, or capacity to advocate for better protections. This capacity to advocate for safe workplaces may account for relatively low mortality rates in potentially high-risk occupations. Future research should examine factors determining worker complaints and complaint systems to promote participation of those with the greatest need of protection.
Production of novel Spike truncations in Chinese hamster ovary cells
Authors: Minami Shiaki A. , Jung Seongwon , Huang Yihan , Harris Bradley S. , Kenaston Matthew W. , Faller Roland , Nandi Somen , McDonald Karen A. , Shah Priya S. 
Published: December 2021

AbstractSARS-CoV-2 Spike is a key protein that mediates viral entry into cells and elicits antibody responses. Its importance in infection, diagnostics, and vaccinations has created a large demand for purified Spike for clinical and research applications. Spike is difficult to express, prompting modifications to the protein and expression platforms to improve yields. Alternatively, Spike receptor binding domain (RBD) is commonly expressed with higher titers, though it has lower sensitivity in serological assays. Here, we improve transient Spike expression in Chinese hamster ovary (CHO) cells. We demonstrate that Spike titers increase significantly over the expression period, maximizing at 14 mg/L at day 7. In comparison, RBD titers peak at 54 mg/L at day 3. Next, we develop 8 Spike truncations (T1-T8) in pursuit of a truncation with high expression and antibody binding. The truncations T1 and T4 express at 130 mg/L and 73 mg/L, respectively, which are higher than our RBD titers. Purified proteins were evaluated for binding to antibodies raised against full-length Spike. T1 has similar sensitivity as Spike against a monoclonal antibody and even outperforms Spike for a polyclonal antibody. These results suggest T1 is a promising Spike alternative for use in various applications.
Diversity in Parkinson’s disease genetics research: current landscape and future directions
Authors: Schumacher-Schuh Artur F. , Bieger Andrei , Okunoye Olaitan , Mok Kin , Lim Shen-Yang , Bardien Soraya , Annuar Azlina Ahmad , Lopes-Santos Bruno , Strelow Matheus Zschornack , Salama Mohamed , Rao Shilpa C , Zewde Yared Zenebe , Dindayal Saiesha , Azar Jihan , Prashanth LK , Rajan Roopa , Noyce Alastair J , Okubadejo Njideka , Rizig Mie , Lesage Suzanne , Mata Ignacio 
Published: December 2021

AbstractHuman genetics research lacks diversity; over 80% of genome-wide association studies (GWAS) have been conducted on individuals of European ancestry. In addition to limiting insights regarding disease mechanisms, disproportionate representation can create disparities preventing equitable implementation of personalized medicine. This systematic review provides an overview of research involving Parkinson’s disease (PD) genetics in under-represented populations (URP), and sets a baseline to measure the future impact of current efforts in those populations.We searched PubMed and EMBASE until October 2021 using search strings for “PD”, “genetics”, the main “URP”, and “lower-to-upper-middle-income countries”. Inclusion criteria were original studies, written in English, reporting genetic results on PD patients from non-European populations. Two levels of independent reviewers identified and extracted relevant information.We observed considerable imbalances in PD genetic studies among URP. Asian participants from China were described in the majority of the articles published (61%), but other populations were less well studied, for example, Blacks were represented in just 4.0% of the publications. Also, although idiopathic PD was more studied than monogenic forms of the disease, most studies analyzed a limited number of genetic variants. We identified just seven studies using a genome-wide approach published up to 2021 including URP.This review provides insight into the significant lack of population diversity in PD research highlighting the urgent need for better representation. The Global Parkinson’s Genetics Program (GP2) and similar initiatives aim to impact research in URP, and the early metrics presented here can be used to measure progress in the field of PD genetics in the future.
A novel approach to concentrate human and animal viruses from wastewater using receptors-conjugated magnetic beads
Authors: Oh Chamteut , Kim Kyukyoung , Araud Elbashir , Wang Leyi , Shisler Joanna L. , Nguyen Thanh H. 
Published: December 2021

AbstractViruses are present at low concentrations in wastewater, and therefore an effective concentration of virus particles is necessary for accurate wastewater-based epidemiology (WBE). We designed a novel approach to concentrate human and animal viruses from wastewater using porcine gastric mucin-conjugated magnetic beads (PGM-MBs). We systematically evaluated the performances of the PGM-MBs method (sensitivity, specificity, and robustness to environmental inhibitors) with six viral species including Tulane virus (a surrogate for human norovirus), rotavirus, adenovirus, porcine coronavirus (transmissible gastroenteritis virus or TGEV), and two human coronaviruses (NL63 and SARS-CoV-2) in influent wastewater and raw sewage samples. We determined the multiplication factor (the ratio of genome concentration of the concentrated over that of the initial solution) for the PGM-MBs method, which ranged from 1.3 to 64.0 depending on the viral species. Because the recovery efficiency became significantly higher when calculated based on virus titers than genome concentration, the PGM-MBs method could be an appropriate tool for assessing the risk due to wastewater contaminated with infectious enteric viruses. PCR inhibitors were not concentrated by PGM-MBs, suggesting this tool will be successful for use with environmental samples. The PGM-MBs method is cost-effective (0.43 USD/sample) and fast turnaround (3 hours from virus concentration to genome quantification), and thus this method can be implemented for high throughput facilities. Based on good performance, intrinsic characteristics of targeting the infectious virus, robustness to wastewater, and adaptability to high throughput systems, we are confident that the PGM-MBs method can be applied for successful WBE and ultimately provides valuable public health information.Graphical abstract
Transparent and Conformal Microcoil Arrays for Spatially Selective Neuronal Activation
Authors: Raghuram Vineeth , Datye Aditya D. , Fried Shelley I. , Timko Brian P. 
Published: December 2021

SummaryMicromagnetic stimulation (μMS) using small, implantable microcoils is a promising modality for achieving neuronal activation with high spatial resolution and low toxicity. Microcoils can be designed to achieve localized, spatially asymmetric fields that target neurons of a particular orientation. Insulation of the coil avoids the direct contact between metal and tissue and the use of specialized biopolymers may help to further reduce chronic inflammation and glial scarring. Studies to date have largely focused on single channel devices; herein, we report the design and development of a microcoil array for localized activation of cortical neurons and retinal ganglion cells. We utilized a computational model that related the activation function to the geometry and arrangement of coils and selected a coil design that maintained a region of activation <50 µm wide. The device was composed of an SU8/Cu/SU8 tri-layer structure, which was flexible, transparent and conformal and featured four individually-addressable microcoil stimulation elements. Interfaced with ex vivo cortex or retina slices from GCaMP6-transfected mice, we observed that individual neurons localized within 40 µm of the element tip could be activated repeatedly and in a dose (power) dependent fashion. Taken together, these results highlight the potential of magnetic stimulation devices for brain-machine interfaces and could open new routes toward bioelectronic therapies including prosthetic vision devices.
Analyses of the Autism-associated Neuroligin-3 R451C Mutation in Human Neurons Reveals a Gain-of-Function Synaptic Mechanism
Authors: Wang Le , Mirabella Vincent R. , Dai Rujia , Su Xiao , Xu Ranjie , Jadali Azadeh , Bernabucci Matteo , Singh Ishnoor , Chen Yu , Tian Jianghua , Jiang Peng , Kwan Kevin Y. , Pak ChangHui , Liu Chunyu , Comoletti Davide , Hart Ronald P. , Chen Chao , Südhof Thomas C. , Pang Zhiping P. 
Published: December 2021

AbstractMutations in many synaptic genes are associated with autism spectrum disorders (ASDs), suggesting that synaptic dysfunction is a key driver of ASD pathogenesis. Among these mutations, the R451C-substitution in the NLGN3 gene that encodes the postsynaptic adhesion molecule Neuroligin-3 is noteworthy because it was the first specific mutation linked to ASDs. In mice, the corresponding Nlgn3 R451C-knockin mutation recapitulates social interaction deficits of ASD patients and produces synaptic abnormalities, but the impact of the NLGN3 R451C-mutation on human neurons has not been investigated. Here, we generated human knock-in neurons with the NLGN3 R451C-mutation. Strikingly, analyses of NLGN3 R451C-mutant neurons revealed that the R451C-mutation decreased NLGN3 protein levels but enhanced the strength of excitatory synapses without affecting inhibitory synapses. No significant cell death and endoplasmic reticulum stress were detected. Importantly, the augmentation of excitatory transmission was confirmed in vivo with human neurons transplanted into mouse forebrain.Using single-cell RNA-seq experiments with co-cultured excitatory and inhibitory NLGN3 R451C-mutant neurons, we identified differentially expressed genes in relatively mature human neurons that corresponded to synaptic gene expression networks. Moreover, gene ontology and enrichment analyses revealed convergent gene networks associated with ASDs and other mental disorders. Our findings suggest that the NLGN3 R451C-mutation induces a gain-of-function enhancement in excitatory synaptic transmission that may contribute to the pathophysiology of ASDs.
Attentive deep learning-based tumor-only somatic mutation classifier achieves high accuracy agnostic of tissue type and capture kit
Authors: McLaughlin R. Tyler , Asthana Maansi , Meo Marc Di , Ceccarelli Michele , Jacob Howard J. , Masica David L. 
Published: December 2021

AbstractIn precision oncology, reliable identification of tumor-specific DNA mutations requires sequencing tumor DNA and non-tumor DNA (so-called “matched normal”) from the same patient. The normal sample allows researchers to distinguish acquired (somatic) and hereditary (germline) variants. The ability to distinguish somatic and germline variants facilitates estimation of tumor mutation burden (TMB), which is a recently FDA-approved pan-cancer marker for highly successful cancer immunotherapies; in tumor-only variant calling (i.e., without a matched normal), the difficulty in discriminating germline and somatic variants results in inflated and unreliable TMB estimates. We apply machine learning to the task of somatic vs germline classification in tumor-only samples using TabNet, a recently developed attentive deep learning model for tabular data that has achieved state of the art performance in multiple classification tasks (Arik and Pfister 2019). We constructed a training set for supervised classification using features derived from tumor-only variant calling and drawing somatic and germline truth-labels from an independent pipeline incorporating the patient-matched normal samples. Our trained model achieved state-of-the-art performance on two hold-out test datasets: a TCGA dataset including sarcoma, breast adenocarcinoma, and endometrial carcinoma samples (F1-score: 88.3), and a metastatic melanoma dataset, (F1-score 79.8). Concordance between matched-normal and tumor-only TMB improves from R2 = 0.006 to 0.705 with the addition of our classifier. And importantly, this approach generalizes across tumor tissue types and capture kits and has a call rate of 100%. The interpretable feature masks of the attentive deep learning model explain the reasons for misclassified variants. We reproduce the recent finding that tumor-only TMB estimates for Black patients are extremely inflated relative to that of White patients due to the racial biases of germline databases. We show that our machine learning approach appreciably reduces this racial bias in tumor-only variant-calling.
Vascular proteome responses precede organ dysfunction in sepsis
Authors: Sorrentino James T. , Golden Gregory J. , Morris Claire , Painter Chelsea , Nizet Victor , Campos Alexandre Rosa , Smith Jeffrey W. , Karlsson Christofer , Malmström Johan , Lewis Nathan E. , Esko Jeffrey D. , Toledo Alejandro Gómez 
Published: December 2021

AbstractVascular dysfunction and organ failure are two distinct, albeit highly interconnected clinical outcomes linked to morbidity and mortality in human sepsis. The mechanisms driving vascular and parenchymal damage are dynamic and display significant molecular crosstalk between organs and tissues. Therefore, assessing their individual contribution to disease progression is technically challenging. Here, we hypothesize that dysregulated vascular responses predispose the organism to organ failure. To address this hypothesis, we have evaluated four major organs in a murine model of S. aureus sepsis by combining in vivo labeling of the endothelial proteome, data-independent acquisition (DIA) mass spectrometry, and an integrative computational pipeline. The data reveal, with unprecedented depth and throughput, that a septic insult evokes organ-specific proteome responses that are highly compartmentalized, synchronously coordinated, and significantly correlated with the progression of the disease. Vascular proteome changes were found to precede bacterial invasion and leukocyte infiltration into the organs, as well as to precede changes in various well-established cellular and biochemical correlates of systemic coagulopathy and tissue dysfunction. Importantly, our data suggests a potential role for the vascular proteome as a determinant of the susceptibility of the organs to undergo failure during sepsis.
Early detection of sublexical and lexical processing in beginning readers: evidence from Steady-State Visual Evoked Potentials (SSVEPs)
Authors: Wang Fang , Nguyen Quynh Trang H. , Kaneshiro Blair , Hasak Lindsey , Wang Angie M. , Toomarian Elizabeth Y. , Norcia Anthony M. , McCandliss Bruce D. 
Published: December 2021

AbstractThere are multiple levels of processing relevant to reading that vary in their visual, sublexical and lexical orthographic processing demands. Segregating distinct cortical sources for each of these levels has been challenging in EEG studies of early readers. To address this challenge, we applied recent advances in analyzing high-density EEG using Steady-State Visual Evoked Potentials (SSVEPs) via data-driven Reliable Components Analysis (RCA) in a group of early readers spanning from kindergarten to second grade. Three controlled stimulus contrasts—familiar words versus unfamiliar pseudofonts, familiar words versus orthographically legal pseudowords, and orthographically legal pseudowords versus orthographically illegal nonwords—were used to isolate visual print/letter selectivity, sublexical processing, and lexical processing, respectively. We found robust responses specific to each of these processing levels, even in kindergarteners who have limited knowledge of print. Moreover, comparing amplitudes of these three stimulus contrasts across three reading fluency-based groups and three grade-based groups revealed fluency group and grade group main effects only for lexical contrast (i.e., words versus orthographically legal pseudowords). Furthermore, we found that sublexical orthography-related responses shifted their topographic distribution from the right to left hemisphere from kindergarten to first and second grades. Results suggest that, with more sensitive measures, the sublexical and lexical fine tuning for words—as a bio-marker of reading ability—can be detected at a much earlier stage than previously assumed.Declarations of interestNone
Multifaceted effects of variable biotic interactions on population stability in complex interaction webs
Authors: Hashimoto Koya , Hayasaka Daisuke , Eguchi Yuji , Seko Yugo , Cai Ji , Suzuki Kenta , Goka Koichi , Kadoya Taku 
Published: December 2021

AbstractRecent studies have revealed that biotic interactions in ecological communities vary over time, possibly mediating community responses to anthropogenic disturbances. This study investigated the heterogeneity of such variability within a real community and its impact on population stability in the face of pesticide application, particularly focusing on density-dependence of the interaction effect. Using outdoor mesocosms with a freshwater community, we found considerable heterogeneity in density-dependent interaction variability among links in the same community. This variability mediated the stability of recipient populations, with negative density-dependent interaction variability stabilizing whereas positive density-dependence and density-independent interaction variability destabilizing populations. Unexpectedly, the mean interaction strength, which is typically considered crucial for stability, had no significant effect, suggesting that how organisms interact on average is insufficient to predict the ecological impacts of pesticides. Our findings emphasize the multifaceted role of interaction variability in predicting the ecological consequences of anthropogenic disturbances such as pesticide application.
Reassessing referred sensations following peripheral deafferentation and the role of cortical reorganisation
Authors: Amoruso Elena , Terhune Devin B. , Kromm Maria , Kirker Stephen , Muret Dollyane , Makin Tamar R. 
Published: December 2021

ABSTRACTBackground and ObjectivesTactile sensations referred to body parts other than those stimulated have been repeatedly described across a wide range of deafferentation and neuropathic pain conditions, including amputation, complex regional pain syndrome, spinal cord injury, and brachial plexus avulsion. Common to all interpretations of referred sensations is the notion that they result from central nervous system (CNS) reorganisation. For example, in amputees, sensations referred to the phantom limb following touches on the face have been classically interpreted as the perceptual correlate of cortical remapping of the face into the neighbouring missing-hand territory in primary somatosensory cortex (S1). Here, using the prominent model of acquired upper-limb amputation, we investigated whether referred sensations reports are associated with cortical remapping or can instead be attributed to demand characteristics (e.g., compliance, expectation, and suggestion), which have been shown to greatly influence self-reports of bodily sensations and were uncontrolled in previous assessments.MethodsUnilateral upper-limb amputees (N=18), congenital one-handers (N=19), and two-handers (N=20) were repeatedly stimulated with PC-controlled vibrations on ten body-parts and asked to report on each trial the occurrence of any concurrent sensations on their hand(s). To further manipulate expectations, we gave participants the suggestion that some of these vibrations had a higher probability to evoke referred sensations. To evaluate remapping, we analysed fMRI data in S1 from two tasks involving movement of facial and whole-body parts, using univariate and multivariate approaches.ResultsThe frequency and distribution of reported referred sensations were similar across groups, with higher frequencies in the high expectancy condition. In amputees, referred sensations were evoked by stimulation of multiple body-parts and reported in both the intact and phantom hand. The group profiles for referred sensations reports were not consistent with the observed patterns of S1 remapping.DiscussionThese findings weaken the interpretation of referred sensations as a perceptual consequence of post-deafferentation CNS reorganisation and reveal the need to account for demand characteristics when evaluating self-reports of anomalous perceptual phenomena for both research and clinical assessments purposes.
Long Noncoding RNA RROL Provides Chromatin Scaffold for MYC-WDR82 Interaction to Impact Lipid Metabolism and Tumor Cell Growth in Multiple Myeloma
Authors: Morelli Eugenio , Fulciniti Mariateresa , Samur Mehmet K. , Ribeiro Caroline F. , Wert-Lamas Leon , Henninger Jon E. , Gullà Annamaria , Aktas-Samur Anil , Todoerti Katia , Talluri Srikanth , Park Woojun D. , Federico Cinzia , Scionti Francesca , Amodio Nicola , Bianchi Giada , Johnstone Megan , Liu Na , Gramegna Doriana , Russo Nicola A. , Lin Charles , Tai Yu-Tzu , Neri Antonino , Chauhan Dharminder , Hideshima Teru , Shammas Masood A. , Tassone Pierfrancesco , Gryaznov Sergei , Young Richard A. , Anderson Kenneth C. , Novina Carl D. , Loda Massimo , Munshi Nikhil C. 
Published: December 2021

SUMMARYLong noncoding RNAs (lncRNA) can drive the tumorigenesis and be susceptible to therapeutic intervention. To define the landscape of therapeutically actionable lncRNA dependencies in multiple myeloma (MM), we coupled our extensive lncRNA transcriptomic profile with lncRNA targeted CRISPR interference viability screen and identified RNA Regulator of Lipogenesis (RROL) as a leading lncRNA dependency in MM. RROL shares its origin with the microRNA locus MIR17HG, however supports the proliferation and survival of MM cells in a microRNA- and DROSHA- independent manner. We found that RROL provides a chromatin scaffold for the functional interaction between c-MYC and WDR82 to promote the regulation of the lipogenic pathways via the transcriptional control of the rate-limiting enzyme ACC1 in MM cells. Inhibition of RROL with clinically applicable antisense molecules disrupts its transcriptional and functional activities causing potent anti-tumor effects both in vitro and in vivo in two pre-clinical animal models. This study establishes lncRNA RROL as a therapeutically actionable dependency with a unique mechanism of action in support of myeloma cell growth.