bluuebunny/crossref_metadata_2025_split huggingface dataset:
Healing Our Own: A Randomized Trial to Assess Benefits of Peer Support
Authors: Rivera-Chiauzzi Enid Y. , Smith Heather A. , Moore-Murray Tanya , Lee Colleen , Goffman Dena , Bernstein Peter S. , Chazotte Cynthia 
Published: September 2020

Objectives
This study aimed to develop and evaluate a structured peer support program to address the needs of providers involved in obstetric adverse outcomes.

Methods
In this pilot randomized controlled trial, participants were providers who experienced an obstetric-related adverse outcome. Providers were randomly assigned to routine support (no further follow-up) or enhanced support (follow-up with a trained peer supporter). Participants completed surveys at baseline, 3 months, and 6 months. The primary outcome was the use of resources and the perception of their helpfulness. Secondary outcomes were the effect on the recovery stages and the duration of use of peer support.

Results
Fifty participants were enrolled and randomly assigned 1:1 to each group; 42 completed the program (enhanced, 23; routine, 19). The 2 groups were not significantly different with respect to event type, demographics, or baseline stage; in both groups, most participants started at the stage 6 thriving path. Most participants required less than 3 months of support: 65.2% did not need follow-up after the first contact, and 91.3% did not need follow-up after the second contact. Participants who transitioned from an early stage of recovery (stages 1–3) to the stage 6 thriving path reported that they most often sought support from peers (P = 0.02) and departmental leadership (P = 0.07). Those in the enhanced support group were significantly more likely to consider departmental leadership as one of the most helpful resources (P = 0.02).

Conclusions
For supporting health care providers involved in adverse outcomes, structured peer support is a practicable intervention that can be initiated with limited resources.
Application of the modified Nutrition Risk in Critically Ill score to nutritional risk stratification of trauma victims: A multicenter observational study
Authors: Iwuchukwu Chinenye , O’Keefe Grant E. , Day Andrew G. , Jiang Xuran , Heyland Daren K. 
Published: September 2020

BACKGROUNDThe modified Nutrition Risk in Critically Ill (mNUTRIC) score was developed to identify patients most likely to benefit from nutritional therapies and to stratify or select study subjects for clinical trials. The score is not validated in trauma victims in whom adequate nutritional support is important and difficult to achieve. We sought to determine whether a higher mNUTRIC score was associated with worse outcomes and whether caloric and protein intake improved outcome more in patients classified as high risk relative to those classified as low risk.METHODSWe analyzed a prospectively collected database of patients from intensive care units globally. The primary outcome was 60-day hospital mortality, and the secondary outcome was time to discharge alive. We compared outcomes between high and low mNUTRIC score groups and also tested whether the association between outcome and nutrition intake was modified by the mNUTRIC score.RESULTSA total of 771 trauma patients were included. Most (585; 76%) had a low-risk mNUTRIC (0–4) score, and 186 (24%) had a high-risk (5–9) mNUTRIC score. The overall 60-day mortality was 13%. Patients in the high mNUTRIC group had a higher risk of death than those in the low mNUTRIC group (adjusted odds ratio, 2.6; 95% confidence interval, 1.7–4.2). Overall, there was no relationship between caloric or protein intake and clinical outcomes. However, patients in the high mNUTRIC group fared better with increasing caloric and protein intake, whereas subjects in the low mNUTRIC score group did not (pvalues for interaction with the mNUTRIC score for time to discharge alive wasp= 0.014 for calories and wasp= 0.004 for protein).CONCLUSIONA high mNUTRIC score identifies trauma patients at higher risk for poor outcomes and those who may benefit from higher caloric and protein intake.LEVEL OF EVIDENCEEpidemiological/Prognostic, level III.
Specific induction of double negative B cells during protective and pathogenic immune responses
Authors: Ruschil Christoph , Gabernet Gisela , Lepennetier Gildas , Heumos Simon , Kaminski Miriam , Hrasko Zsuzsanna , Irmler Martin , Beckers Johannes , Ziemann Ulf , Nahnsen Sven , Owens Greg P. , Bennett Jeffrey L. , Hemmer Bernhard , Kowarik Markus C. 
Published: September 2020

1AbstractDouble negative (DN) (CD19+CD20lowCD27−IgD−) B cells are expanded in patients with autoimmune and infectious diseases; however their role in the humoral immune response remains unclear. Using systematic flow cytometric analyses of peripheral blood B cell subsets, we observed an inflated DN B cell population in patients with variety of active inflammatory conditions: myasthenia gravis, Guillain-Barré syndrome, neuromyelitis optica spectrum disorder, meningitis/encephalitis, and rheumatic disorders. Furthermore, we were able to induce DN B cells in healthy subjects following vaccination against influenza and tick borne encephalitis virus. Transcriptome analysis revealed a gene expression profile in DN B cells that clustered with naïve B cells, memory B cells, and plasmablasts. Immunoglobulin VH transcriptome sequencing and analysis of recombinant antibodies revealed clonal expansion of DN B cells, that were targeted against the vaccine antigen. Our study suggests that DN B cells are expanded in multiple inflammatory neurologic diseases and represent an inducible B cell population that responds to antigenic stimulation, possibly through an extra-follicular maturation pathway.
Transgenerational effect of mutants in the RNA-directed DNA methylation pathway on the triploid block
Authors: Wang Zhenxing , Butel Nicolas , Santos-González Juan , Simon Lauriane , Wärdig Cecilia , Köhler Claudia 
Published: September 2020

AbstractHybridization of plants that differ in number of chromosome sets (ploidy) frequently causes endosperm failure and seed arrest, a phenomenon referred to as triploid block. Mutation inNRPD1, encoding the largest subunit of the plant-specific RNA Polymerase IV (Pol IV), can suppress the triploid block. Pol IV generates short RNAs required to guidede novomethylation in the RNA-directed DNA methylation (RdDM) pathway. In this study, we found that the ability of mutants in the RdDM pathway to suppress the triploid block depends on their degree of inbreeding. Whilenrpd1is able to suppress in the first homozygous generation, mutants inRDR2,NRPE1, andDRM2require at least one additional round of inbreeding to exert a suppressive effect. Inbreeding ofnrpd1was connected with a transgenerational loss of non-CG DNA methylation on sites jointly regulated by CHROMOMETHYLASES 2 and 3. Our data thus reveal that loss of RdDM function differs in its effect in early and late generations and that Pol IV acts at an early stage of triploid block establishment.One-sentence summaryInbreeding of mutants impaired in RdDM components transgenerationally enhanced their ability to suppress the triploid block.
COVID-19 Biomarkers in research: Extension of the OncoMX cancer biomarker data model to capture biomarker data from other diseases
Authors: Gogate N , Lyman D , Crandall K.A , Kahsay R , Natale D.A , Sen S , Mazumder R 
Published: September 2020

AbstractScientists, medical researchers, and health care workers have mobilized worldwide in response to the outbreak of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; SCoV2). Preliminary data have captured a wide range of host responses, symptoms, and lingering problems post-recovery within the human population. These variable clinical manifestations suggest differences in influential factors, such as innate and adaptive host immunity, existing or underlying health conditions, co-morbidities, genetics, and other factors. As COVID-19-related data continue to accumulate from disparate groups, the heterogeneous nature of these datasets poses challenges for efficient extrapolation of meaningful observations, hindering translation of information into clinical applications. Attempts to utilize, analyze, or combine biomarker datasets from multiple sources have shown to be inefficient and complicated, without a unifying resource. As such, there is an urgent need within the research community for the rapid development of an integrated and harmonized COVID-19 Biomarker Knowledgebase. By leveraging data collection and integration methods, backed by a robust data model developed to capture cancer biomarker data we have rapidly crowdsourced the collection and harmonization of COVID-19 biomarkers. Our resource currently has 138 unique biomarkers. We found multiple instances of the same biomarker substance being suggested as multiple biomarker types during our extensive cross-validation and manual curation. As a result, our Knowledgebase currently has 265 biomarker type combinations. Every biomarker entry is made comprehensive by bringing in together ancillary data from multiple sources such as biomarker accessions (canonical UniProtKB accession, PubChem Compound ID, Cell Ontology ID, Protein Ontology ID, NCI Thesaurus Code, and Disease Ontology ID), BEST biomarker category, and specimen type (Uberon Anatomy Ontology) unified with ontology standards. Our preliminary observations show distinct trends in the collated biomarkers. Most biomarkers are related to the immune system (SAA,TNF-∝, and IP-10) or coagulopathies (D-dimer, antithrombin, and VWF) and a few have already been established as cancer biomarkers (ACE2, IL-6, IL-4 and IL-2). These trends align with proposed hypotheses of clinical manifestations compounding the complexity of COVID-19 pathobiology. We explore these trends as we put forth a COVID-19 biomarker resource that will help researchers and diagnosticians alike. All biomarker data are freely available fromhttps://data.oncomx.org/covid19.
Epigenetic Evolution of ACE2 and IL-6 Genes as Non-Canonical Interferon-Stimulated Genes Correlate to COVID-19 Susceptibility in Vertebrates
Authors: Sang Eric R. , Tian Yun , Miller Laura C. , Sang Yongming 
Published: September 2020

AbstractCurrent novel coronavirus disease (COVID-19) has spread globally within a matter of months. The virus establishes a success in balancing its deadliness and contagiousness, and causes substantial differences in susceptibility and disease progression in people of different ages, genders and pre-existing comorbidities. Since these host factors are subjected to epigenetic regulation, relevant analyses on some key genes underlying COVID-19 pathogenesis were performed to longitudinally decipher their epigenetic correlation to COVID-19 susceptibility. The genes of host angiotensin-converting enzyme 2 (ACE2, as the major virus receptor) and interleukin (IL)-6 (a key immune-pathological factor triggering cytokine storm) were shown to evince active epigenetic evolution via histone modification and cis/trans-factors interaction across different vertebrate species. Extensive analyses revealed that ACE2 ad IL-6 genes are among a subset of non-canonical interferon-stimulated genes (non-ISGs), which have been designated recently for their unconventional responses to interferons (IFNs) and inflammatory stimuli through an epigenetic cascade. Furthermore, significantly higher positive histone modification markers and position weight matrix (PWM) scores of keycis-elements corresponding to inflammatory and IFN signaling, were discovered in both ACE2 and IL6 gene promoters across representative COVID-19-susceptible species compared to unsusceptible ones. Findings characterize ACE2 and IL-6 genes as non-ISGs that respond differently to inflammatory and IFN signaling from the canonical ISGs and their epigenetic properties may serve as biomarkers to longitudinally predict COVID-19 susceptibility in vertebrates and partially explain COVID-19 inequality in people of different subgroups.
Does the Inertia of a Cell Depend Upon its Information-Content?
Authors: Elewa Ahmed 
Published: September 2020

ABSTRACTA time dilation factor is derived from information entropy via the holographic principle. By imagining the embryonic cell as a hologram, time dilation during embryogenesis is predicted from the entropy of active genetic information and shown to be consistent with observed lengths of cell duration. The connection between entropy and cell duration as well as the corollary of increase in cellular mass with the reduction in information entropy are discussed. This preprint is the second in a series exploring the value ofDevelopmental Spacetimeas a framework for falsifiable predictions about the universe.
Generation of nonlinear and spatially-organized 3D cultures on a microfluidic chip using photoreactive thiol-ene and methacryloyl hydrogels
Authors: Ortiz-Cárdenas Jennifer E. , Zatorski Jonathan M. , Arneja Abhinav , Montalbine Alyssa N. , Munson Jennifer M. , Luckey Chance John , Pompano Rebecca R. 
Published: September 2020

AbstractMicropatterning techniques for 3D cell cultures enable the recreation of tissue-level structures, but their combination with well-defined, microscale fluidic systems for perfusion remains challenging. To address this technological gap, we developed a user-friendly in-situ micropatterning protocol that integrates photolithography of crosslinkable, cell-laden hydrogels with a simple microfluidic housing, and tested the impact of crosslinking chemistry on stability and spatial resolution. Working with gelatin functionalized with photo-crosslinkable moieties, we found that inclusion of cells at high densities (≥ 107/mL) during crosslinking did not impede thiol-norbornene gelation, but decreased the storage moduli of methacryloyl hydrogels. Hydrogel composition and light dose were selected to match the storage moduli of soft tissues. The cell-laden precursor solution was flowed into a microfluidic chamber and exposed to 405 nm light through a photomask to generate the desired pattern. The on-chip 3D cultures were self-standing, and the designs were interchangeable by simply swapping out the photomask. Thiol-ene hydrogels yielded highly accurate feature sizes from 100 – 900 μm in diameter, whereas methacryloyl hydrogels yielded slightly enlarged features. Furthermore, only thiol-ene hydrogels were mechanically stable under perfusion overnight. Repeated patterning readily generated multi-region cultures, either separately or adjacent, including non-linear boundaries that are challenging to obtain on-chip. As a proof-of-principle, primary human T cells, were patterned on-chip with high regional specificity. Viability remained high (> 85%) after overnight culture with constant perfusion. We envision that this technology will enable researchers to pattern 3D cultures under fluidic control in biomimetic geometries that were previously difficult to obtain.
Back to the future: a refined single user photostation for massively scaling herbarium digitization
Authors: Davis Charles C. , Kennedy Jonathan A. , Grassa Christopher J. 
Published: September 2020

SummaryThe digitization and online mobilization of herbarium specimens has greatly facilitated their access and helped ignite a revolution in the biodiversity sciences (Drew et al., 2017; Hedrick et al., 2020; Nelson et al., 2015; Soltis, 2017; Sweeney et al., 2018; Thiers et al., 2016). These efforts have mobilized millions of specimens with significant economies of scale and accelerated advances in scientific investigations, including phenological studies of climate change, species range assessments, and biotic interactions (Hedrick et al., 2020; Meineke et al., 2019; Meineke et al., 2018; Pearson et al., 2020; Willis et al., 2017). In addition, the use of natural history collections to answer scientific questions using only their digitized representation, rather than the physical specimen itself–i.e., Digitization 2.0sensuHedrick et al. (2020)–has sparked the integration and development of new scholarly disciplines and lines of inquiry not previously possible. Despite these exciting new directions, however, Digitization 1.0sensuHedrick et al. (2020)–i.e., the generation of digitized products from the physical specimen–remains an active area of innovation and development. This relates to both hardware and workflow innovations as well as their integration with advancements in software. Along these lines, innovations in these areas have greatly increased the cost-effectiveness of digitizing herbarium specimens and enabled the successful mobilization of entire collections and whole floristic regions (Heerlien et al., 2015; Pignal and Michiels, 2012; Schorn et al., 2016; Slijkhuis, 2014; Sweeney et al., 2018; van Oever and Gofferjé, 2012). Here, we present a novel photostation and workstation design for imaging herbarium specimen that represents a dramatic improvement upon existing approaches and is scalable for large and small institutions alike.
Myogenic Vasoconstriction Requires Canonical Gq/11Signaling of the Angiotensin II Type 1a Receptor in the Murine Vasculature
Authors: Cui Yingqiu , Kassmann Mario , Nickel Sophie , Zhang Chenglin , Alenina Natalia , Anistan Yoland Marie , Schleifenbaum Johanna , Bader Michael , Welsh Donald G. , Huang Yu , Gollasch Maik 
Published: September 2020

AbstractBackgroundThe myogenic response is an inherent vasoconstrictive property of resistance arteries to keep blood flow constant in response to increases in intravascular pressure. Angiotensin II (Ang II) type 1 receptors (AT1R) are broadly distributed, mechanoactivated receptors, which have been proposed to transduce myogenic vasoconstriction. However, the AT1R subtype(s) involved and their downstream G protein- and β-arrestin-mediated signaling pathways are still elusive.ObjectiveTo characterize the function of AT1aR and AT1bR in the regulation of the myogenic response of resistance size arteries and possible downstream signaling cascades mediated by Gq/11and/or β-arrestins.MethodsWe usedAgtr1a-/-,Agtr1b-/-and tamoxifen-inducible smooth muscle-specific AT1aR knockout mice (SM-Agtr1amice). FR900359, [Sar1, Ile4, Ile8] Ang II (SII) and TRV120055 were used as selective Gq/11protein inhibitor and biased agonists to activate non-canonical β-arrestin and canonical Gq/11signaling of the AT1R, respectively.ResultsMyogenic and Ang II-induced vasoconstrictions were diminished in the perfused renal vasculature ofAgtr1a-/-andSM-Agtr1amice. Similar results were observed in isolated pressurized mesenteric and cerebral arteries. Myogenic tone and Ang II-induced vasoconstrictions were normal in arteries fromAgtr1b-/-mice. The Gq/11blocker FR900359 decreased myogenic tone and Ang II vasoconstrictions while selective biased targeting of AT1R β-arrestin signaling pathways had no effects.ConclusionThe present study demonstrates that myogenic arterial constriction requires Gq/11-dependent signaling pathways of mechanoactivated AT1aR but not G protein-independent, noncanonical alternative signaling pathways in the murine mesenteric, cerebral and renal circulation.
New insights into homoeologous copy number variations in the hexaploid wheat genome
Authors: Juery Caroline , Concia Lorenzo , De Oliveira Romain , Papon Nathan , Ramírez-González Ricardo , Benhamed Moussa , Uauy Cristobal , Choulet Frédéric , Paux Etienne 
Published: September 2020

AbstractBread wheat is an allohexaploid species originating from two successive and recent rounds of hybridization between three diploid species that were very similar in terms of chromosome number, genome size, TE content, gene content and synteny. As a result, it has long been considered that most of the genes were in three pairs of homoeologous copies. However, these so-called triads represent only one half of wheat genes, while the remaining half belong to homoeologous groups with various number of copies across subgenomes. In this study, we examined and compared the distribution, conservation, function, expression and epigenetic profiles of triads with homoeologous groups having undergone a deletion (dyads) or a duplication (tetrads) in one subgenome. We show that dyads and tetrads are mostly located in distal regions and have lower expression level and breadth than triads. Moreover, they are enriched in functions related to adaptation and more associated with the repressive H3K27me3 modification. Altogether, these results suggest that triads mainly correspond to housekeeping genes and are part of the core genome, while dyads and tetrads belong to theTriticeaedispensable genome. In addition, by comparing the different categories of dyads and tetrads, we hypothesize that, unlike most of the allopolyploid species, subgenome dominance and biased fractionation are absent in hexaploid wheat. Differences observed between the three subgenomes are more likely related to two successive and ongoing waves of post-polyploid diploidization, that had impacted A and B more significantly than D, as a result of the evolutionary history of hexaploid wheat.Core ideasOnly one half of hexaploid wheat genes are in triads,i.e. in a 1:1:1 ratio across subgenomesTriads are likely part of the core genome; dyads and tetrads belong to the dispensable genomeSubgenome dominance and biased fractionation are absent in hexaploid wheatSubgenome differences are related to two successive waves of post-polyploid diploidization
Inhibiting DDX3X triggers tumor-intrinsic type I interferon response and enhances anti-tumor immunity
Authors: Choi Hyeongjwa , Kwon Juntae , Sun Jiafang , Cho Min Soon , Sun Yifan , Casey John L , Toretsky Jeffrey , Han Cecil 
Published: September 2020

ABSTRACTAccumulating evidence has shown that cellular double-stranded RNAs (dsRNAs) induce antiviral innate immune responses in human normal and malignant cancer cells. However, it is not fully understood how endogenous ‘self’ dsRNA homeostasis is regulated in the cell. Here, we show that an RNA-binding protein, DEAD-box RNA helicase 3X (DDX3X), prevents the aberrant accumulation of cellular dsRNAs. Loss of DDX3X induces dsRNA sensor-mediated type I interferon signaling and innate immune response in breast cancer cells due to abnormal cytoplasmic accumulation of dsRNAs. Dual depletion of DDX3X and a dsRNA-editing protein, ADAR1 synergistically activates the cytosolic dsRNA pathway in breast cancer cell. Moreover, inhibiting DDX3X enhances the antitumor activity by increasing tumor intrinsic-type I interferon response, antigen presentation, and tumor-infiltration of cytotoxic T cells as well as dendritic cells in breast tumors, which may lead to the development of breast cancer therapy by targeting DDX3X in combination with immune checkpoint blockade.