bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adding stress biomarkers to high-sensitivity cardiac troponin for rapid non-ST-elevation myocardial infarction rule-out protocols
Authors: Restan Ingar Ziad , Sanchez Ana Yufera , Steiro Ole-Thomas , Lopez-Ayala Pedro , Tjora Hilde L , Langørgen Jørund , Omland Torbjørn , Boeddinghaus Jasper , Nestelberger Thomas , Koechlin Luca , Collinson Paul , Bjørneklett Rune , Vikenes Kjell , Strand Heidi , Skadberg Øyvind , Mjelva Øistein R , Larsen Alf Inge , Bonarjee Vernon V S , Mueller Christian , Aakre Kristin M 
Published: December 2021

Abstract

Aims
This study tested the hypothesis that combining stress-induced biomarkers (copeptin or glucose) with high-sensitivity cardiac troponin (hs-cTn) increases diagnostic accuracy for non-ST-elevation myocardial infarction (NSTEMI) in patients presenting to the emergency department.

Methods and results
The ability to rule-out NSTEMI for combinations of baseline hs-cTnT or hs-cTnI with copeptin or glucose was compared with the European Society of Cardiology (ESC) hs-cTnT/I-only rule-out algorithms in two independent (one Norwegian and one international multicentre) diagnostic studies. Among 959 patients (median age 64 years, 60.5% male) with suspected NSTEMI in the Norwegian cohort, 13% had NSTEMI. Adding copeptin or glucose to hs-cTnT/I as a continuous variable did not improve discrimination as quantified by the area under the curve {e.g. hs-cTnT/copeptin 0.91 [95% confidence interval (CI) 0.89–0.93] vs. hs-cTnT alone 0.91 (95% CI 0.89–0.93); hs-cTnI/copeptin 0.85 (95% CI 0.82–0.87) vs. hs-cTnI alone 0.93 (95% CI 0.91–0.95)}, nor did adding copeptin &lt;9 mmol/L or glucose &lt;5.6 mmol/L increase the sensitivity of the rule-out provided by hs-cTnT &lt;5 ng/L or hs-cTnI &lt;4 ng/L in patients presenting more than 3 h after chest pain onset (target population in the ESC-0 h-algorithm). The combination decreased rule-out efficacy significantly (both P &lt; 0.01). These findings were confirmed among 1272 patients (median age 62 years, 69.3% male) with suspected NSTEMI in the international validation cohort, of which 20.7% had NSTEMI. A trend towards increased sensitivity for the hs-cTnT/I/copeptin combinations (97–100% vs. 91–97% for the ESC-0 h-rule-out cut-offs) was observed in the Norwegian cohort.

Conclusion
Adding copeptin or glucose to hs-cTnT/I did not increase diagnostic performance when compared with current ESC guideline hs-cTnT/I-only 0 h-algorithms.
Sex differences in clinical profile, management, and outcomes of patients hospitalized for atrial fibrillation in the United States
Authors: Noubiap Jean Jacques , Thomas Gijo , Agbaedeng Thomas A , Fitzgerald John L , Gallagher Celine , Middeldorp Melissa E , Sanders Prashanthan 
Published: December 2021

Abstract

Aims
This study aimed to investigate the impact of sex on the clinical profile, utilization of rhythm control therapies, cost of hospitalization, length of stay, and in-hospital mortality in patients admitted for atrial fibrillation (AF) in the United States.

Methods and results
We used data from the Nationwide Inpatient Sample for the year 2018. Regression analysis was performed to investigate differences between men and women. A P-value ≤ 0.05 was considered significant. We included 82592 patients with a primary diagnosis of of AF 50.8% women. Women were significantly older (mean age 74 vs. 67 years, P &lt; 0.001) and had a higher CHA2DS2-VASc score (median 4 vs. 2, P &lt; 0.001) than men. Women had relatively higher in-hospital mortality (0.9% vs. 0.8%, P = 0.070); however, after adjustment for known risk factors female sex was no longer a predictor of mortality (P = 0.199). In sex-specific regression analyses, increased age, chronic obstructive pulmonary disease, previous stroke, heart failure, and chronic kidney disease were risk factors for in-hospital mortality in both sexes, vascular disease only in women, and race and alcohol abuse only in men. After adjusting for potential confounders, female sex was associated with lower likelihood of receiving catheter ablation [adjusted odds ratio (aOR) 0.69, 95% confidence interval (CI) 0.64–0.74] and electrical cardioversion (aOR 0.69, 95% CI 0.67–0.72), and with longer hospitalization (aOR 1.33, 95% CI 1.28–1.37), whereas sex had no influence on hospitalization costs (P = 0.339).

Conclusion
There were differences in the risk profile, management, and outcomes between men and women hospitalized for AF. Further studies are needed to explore why women are treated differently regarding rhythm control procedures.
Skin bacterial metacommunities of San Francisco Bay Area salamanders are structured by host genus and habitat quality
Authors: Buttimer Shannon , Hernández-Gómez Obed , Rosenblum Erica Bree 
Published: December 2021

ABSTRACT
Host-associated microbial communities can influence physiological processes of macroorganisms, including contributing to infectious disease resistance. For instance, some bacteria that live on amphibian skin produce antifungal compounds that inhibit two lethal fungal pathogens, Batrachochytrium dendrobatidis (Bd) and Batrachochytrium salamandrivorans (Bsal). Therefore, differences in microbiome composition among host species or populations within a species can contribute to variation in susceptibility to Bd/Bsal. This study applies 16S rRNA sequencing to characterize the skin bacterial microbiomes of three widespread terrestrial salamander genera native to the western United States. Using a metacommunity structure analysis, we identified dispersal barriers for these influential bacteria between salamander families and localities. We also analysed the effects of habitat characteristics such as percent natural cover and temperature seasonality on the microbiome. We found that certain environmental variables may influence the skin microbial communities of some salamander genera more strongly than others. Each salamander family had a somewhat distinct community of putative anti-Bd skin bacteria, suggesting that salamanders may select for a functional assembly of cutaneous symbionts that could differ in its ability to protect these amphibians from disease. Our observations raise the need to consider host identity and environmental heterogeneity during the selection of probiotics to treat wildlife diseases.
Strong reorganization of multi-domain microbial networks associated with primary producers sedimentation from oxic to anoxic conditions in an hypersaline lake
Authors: Escalas Arthur , Troussellier Marc , Melayah Delphine , Bruto Maxime , Nicolas Sébastien , Bernard Cécile , Ader Magali , Leboulanger Christophe , Agogué Hélène , Hugoni Mylène 
Published: December 2021

ABSTRACT
Understanding the role of microbial interactions in the functioning of natural systems is often impaired by the levels of complexity they encompass. In this study, we used the relative simplicity of an hypersaline crater lake hosting only microbial organisms (Dziani Dzaha) to provide a detailed analysis of the microbial networks including the three domains of life. We identified two main ecological zones, one euphotic and oxic zone in surface, where two phytoplanktonic organisms produce a very high biomass, and one aphotic and anoxic deeper zone, where this biomass slowly sinks and undergoes anaerobic degradation. We highlighted strong differences in the structure of microbial communities from the two zones and between the microbial consortia associated with the two primary producers. Primary producers sedimentation was associated with a major reorganization of the microbial network at several levels: global properties, modules composition, nodes and links characteristics. We evidenced the potential dependency of Woesearchaeota to the primary producers’ exudates in the surface zone, and their disappearance in the deeper anoxic zone, along with the restructuration of the networks in the anoxic zone toward the decomposition of the organic matter. Altogether, we provided an in-depth analysis of microbial association network and highlighted putative changes in microbial interactions supporting the functioning of the two ecological zones in this unique ecosystem.
Resistance of Perfluorooctanoic Acid to Degradation by the Microbially-Driven Fenton Reaction
Authors: Toporek Yael , Shin Hyun-Dong , DiChristina Thomas J 
Published: December 2021

Abstract
Per- and polyfluoroalkyl substances (PFAS) such as perfluorooctanoic acid (PFOA) have received recent heightened attention as emerging contaminants. Due to widespread application in household products and aqueous film-forming foams, PFAS are globally distributed in the environment, and bioaccumulate in the blood and tissues of mammals including humans. The microbially-driven Fenton reaction, a hybrid biotic/abiotic hydroxyl radical (HO•)-generating system, previously degraded a wide variety of persistant organic pollutants. In the present study, the microbially driven Fenton reaction was employed to attempt degradation of PFOA. Batch cultures of the facultatively anaerobic bacteria Shewanella oneidensis were amended with PFOA and Fe(III)-citrate. Under aerobic conditions, S. oneidensis reduced oxygen to hydrogen peroxide (H2O2), while under anaerobic conditions, S. oneidensis reduced Fe(III) to Fe(II). During aerobic-to-anaerobic transition periods, Fe(II) and H2O2 interacted chemically via the Fenton reaction to produce HO• radicals, which in turn interacted with PFOA. Batch reactors were cycled between aerobic and anaerobic phases for four cycles, residual PFOA was extracted via liquid-liquid extraction and analyzed by liquid chromatography combined with tandem mass spectrometry. Unlike degradation of other organic pollutants, PFOA concentrations remained unchanged, which indicated that PFOA was resistant to degradation by the microbially-driven Fenton reaction. Similar to abiotic (purely chemical) Fenton reaction systems, these results most likely reflect the inability of HO• radicals to oxidatively degrade PFOA.
Assembled and annotated 26.5 Gbp coast redwood genome: a resource for estimating evolutionary adaptive potential and investigating hexaploid origin
Authors: Neale David B , Zimin Aleksey V , Zaman Sumaira , Scott Alison D , Shrestha Bikash , Workman Rachael E , Puiu Daniela , Allen Brian J , Moore Zane J , Sekhwal Manoj K , De La Torre Amanda R , McGuire Patrick E , Burns Emily , Timp Winston , Wegrzyn Jill L , Salzberg Steven L 
Published: December 2021

AbstractSequencing, assembly, and annotation of the 26.5 Gbp hexaploid genome of coast redwood (Sequoia sempervirens) was completed leading toward discovery of genes related to climate adaptation and investigation of the origin of the hexaploid genome. Deep-coverage short-read Illumina sequencing data from haploid tissue from a single seed were combined with long-read Oxford Nanopore Technologies sequencing data from diploid needle tissue to create an initial assembly, which was then scaffolded using proximity ligation data to produce a highly contiguous final assembly, SESE 2.1, with a scaffold N50 size of 44.9 Mbp. The assembly included several scaffolds that span entire chromosome arms, confirmed by the presence of telomere and centromere sequences on the ends of the scaffolds. The structural annotation produced 118,906 genes with 113 containing introns that exceed 500 Kbp in length and one reaching 2 Mb. Nearly 19 Gbp of the genome represented repetitive content with the vast majority characterized as long terminal repeats, with a 2.9:1 ratio of Copia to Gypsy elements that may aid in gene expression control. Comparison of coast redwood to other conifers revealed species-specific expansions for a plethora of abiotic and biotic stress response genes, including those involved in fungal disease resistance, detoxification, and physical injury/structural remodeling and others supporting flavonoid biosynthesis. Analysis of multiple genes that exist in triplicate in coast redwood but only once in its diploid relative, giant sequoia, supports a previous hypothesis that the hexaploidy is the result of autopolyploidy rather than any hybridizations with separate but closely related conifer species.
Transnationalizing fascist martyrs: an entangled history of the memorialization of Ion Moţa and Vasile Marin in Spain and Romania, 1937–41
Authors: Zavatti Francesco 
Published: December 2021

Abstract
This article analyses the memorialization of Ion Moţa and Vasile Marin, two Romanian Legionary movement volunteers who died while fighting for Franco in the Spanish Civil War, as an entangled history of Romanian and Spanish fascisms. The commemoration practices and narratives recounted in the Spanish and Romanian newspapers and archival sources from the period 1937–41 show that commemorating foreign ideological peers and appropriating symbolic elements of foreign fascisms in order to memorialize fallen comrades served as resources for legitimizing the struggle against domestic competitors. Although the totalitarian ambitions of Spanish and Romanian fascists remained unfulfilled, the Spanish-Romanian entanglement contributed to consolidating Moţa and Marin as martyrs of transnational fascism.
Immunological Regulation of Intestinal Fibrosis in Inflammatory Bowel Disease
Authors: Bamias Giorgos , Pizarro Theresa T , Cominelli Fabio 
Published: December 2021

Abstract
Intestinal fibrosis is a late-stage phenotype of inflammatory bowel disease (IBD), which underlies most of the long-term complications and surgical interventions in patients, particularly those with Crohn’s disease. Despite these issues, antifibrotic therapies are still scarce, mainly due to the current lack of understanding concerning the pathogenetic mechanisms that mediate fibrogenesis in patients with chronic intestinal inflammation. In the current review, we summarize recent evidence regarding the cellular and molecular factors of innate and adaptive immunity that are considered critical for the initiation and amplification of extracellular matrix deposition and stricture formation. We focus on the role of cytokines by dissecting the pro- vs antifibrotic components of the immune response, while taking into consideration their temporal association to the progressive stages of the natural history of IBD. We critically present evidence from animal models of intestinal fibrosis and analyze inflammation-fibrosis interactions that occur under such experimental scenarios. In addition, we comment on recent findings from large-scale, single-cell profiling of fibrosis-relevant populations in IBD patients. Based on such evidence, we propose future potential targets for antifibrotic therapies to treat patients with IBD.
Protein Kinase CK2 Maintains Reciprocal Balance Between Th17 and Treg Cells in the Pathogenesis of UC
Authors: Dong Guanjun , Yang Yonghong , Zhang Hairong , Yu Wei , He Heng , Dai Fengxian , Ma Cuimei , Wang Yibo , Zhu Fengqin , Xiong Huabao , Zhou Guangxi 
Published: December 2021

Abstract

Background
T helper 17 and regulatory T cells balance have crucial effects on the development of ulcerative colitis (UC). Currently, how to break this balance has not yet been found. Protein kinase CK2 is involved in the pathogenesis of immune-related disorders. However, its effects on the development of UC are obscure.

Methods
The level of CK2 in the colonic tissues of UC patients was quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and immune-histochemistry. Peripheral blood CD4+ T cells were treated with CK2 inhibitor CX4945 or transfected with Csnk2-interfering lentivirus; the mRNA expression and protein levels of inflammatory cytokines were detected by qRT-PCR, enzyme-linked immunosorbent assay, and flow cytometry. Moreover, CX4945 was administered to trinitrobenzene sulfonic acid (TNBS)–induced colitis mice model for determining the function of CK2 on the regulation of intestinal inflammation.

Results
The CK2 level was markedly increased in inflamed mucosa of UC and highly expressed in CD4+ T cells. Blockade of CK2 by CX4945 inhibited Th17 but promoted regulatory T-cell (Treg) immune responses in CD4+ T cells from patients with UC. Moreover, CK2 blockade alleviated TNBS-induced colitis in mice. Inhibition of CK2 suppressed Th17 but promoted Treg differentiation by decreasing the phosphorylation level of signal transducer and activator of transcription (STAT) 3 and increasing the phosphorylation level of STAT5. The RNA-Seq and co-immunoprecipitation analysis further showed that CK2 could interact with Sirtuin 1 (SIRT1) and downregulate SIRT1 expression, which participated in Th17 inhibition but promoted Treg differentiation. Sirtuin 1 upregulation ameliorated TNBS-induced colitis, whereas SIRT1 blockade aggravated TNBS-induced colitis in mice.

Conclusions
CK2 have crucial effects on the development of UC by maintaining reciprocal balance between Th17 and Treg cells. Protein kinase CK2 blockade might be considered as a new therapeutic approach for UC treatment.
Towards Modeling Anhedonia and Its Treatment in Zebrafish
Authors: de Abreu Murilo S , Costa Fabiano , Giacomini Ana C V V , Demin Konstantin A , Zabegalov Konstantin N , Maslov Gleb O , Kositsyn Yuriy M , Petersen Elena V , Strekalova Tatiana , Rosemberg Denis B , Kalueff Allan V 
Published: December 2021

Abstract
Mood disorders, especially depression, are a major cause of human disability. The loss of pleasure (anhedonia) is a common, severely debilitating symptom of clinical depression. Experimental animal models are widely used to better understand depression pathogenesis and to develop novel antidepressant therapies. In rodents, various experimental models of anhedonia have already been developed and extensively validated. Complementing rodent studies, the zebrafish (Danio rerio) is emerging as a powerful model organism to assess pathobiological mechanisms of affective disorders, including depression. Here, we critically discuss the potential of zebrafish for modeling anhedonia and studying its molecular mechanisms and translational implications.
BSAC Vanguard Series: The future of drug development and the tension between access and excess
Authors: Datta Santanu 
Published: December 2021

Abstract
There is a crying need for a new broad-spectrum antibiotic. The global unmet need has energized governments and researchers alike. We may soon have the next antibiotics coming to the aid of patients after a drought of over half a century. However, we need to traverse a complex causeway between access to new antibiotics and their overuse. In an ICU setting where time is premium, identifying the causative organism and its resistance pattern in the time window is often impossible; physicians may be forced to prescribe the latest antibiotics. This practice in the long term may give rise to a rapid spread of resistance among microbes. There is an urgent need to do a cost–benefit analysis of easy access and use of the new antibiotics.
Developing machine learning-based models to help identify child abuse and neglect: key ethical challenges and recommended solutions
Authors: Landau Aviv Y , Ferrarello Susi , Blanchard Ashley , Cato Kenrick , Atkins Nia , Salazar Stephanie , Patton Desmond U , Topaz Maxim 
Published: December 2021

Abstract
Child abuse and neglect are public health issues impacting communities throughout the United States. The broad adoption of electronic health records (EHR) in health care supports the development of machine learning–based models to help identify child abuse and neglect. Employing EHR data for child abuse and neglect detection raises several critical ethical considerations. This article applied a phenomenological approach to discuss and provide recommendations for key ethical issues related to machine learning–based risk models development and evaluation: (1) biases in the data; (2) clinical documentation system design issues; (3) lack of centralized evidence base for child abuse and neglect; (4) lack of “gold standard “in assessment and diagnosis of child abuse and neglect; (5) challenges in evaluation of risk prediction performance; (6) challenges in testing predictive models in practice; and (7) challenges in presentation of machine learning–based prediction to clinicians and patients. We provide recommended solutions to each of the 7 ethical challenges and identify several areas for further policy and research.
Validation of N-LightTM L. monocytogenes for Detection of Listeria monocytogenes on Environmental Surfaces: AOAC Performance Tested MethodSM 122002
Authors: Larose Delphine , Desroche Nicolas , Reinau Lukas , Hupfeld Mario , Fieseler Lars 
Published: December 2021

Abstract

Background
The NEMIS Technologies N-LightTM L. monocytogenes assay uses chemiluminescence designed for the qualitative detection of Listeria monocytogenes from environmental surface samples.

Objective
To validate the NEMIS Technologies N-Light L. monocytogenes assay as part of the AOAC Performance Tested MethodSM program for the detection of L. monocytogenes on stainless steel, plastic (polystyrene), and ceramic environmental surfaces.

Method
Using the Vitl Life Science Solutions Lu-mini luminometer, the NEMIS Technologies N-Light L. monocytogenes assay was compared to the ISO 11290–1:2017: Microbiology of the Food Chain—Horizontal method for the detection and enumeration of Listeria monocytogenes and of Listeria spp. – Part 1 using a 1" × 1" stainless steel test area in an unpaired study design.

Results
The NEMIS Technologies N-Light L. monocytogenes assay using the Vitl Life Science Solutions Lu-mini luminometer demonstrated no statistically significant differences between presumptive and confirmed results or between candidate and reference method results. Data for additional Performance Tested MethodSM studies met acceptance criteria requirements.

Conclusions
The NEMIS Technologies N-Light L. monocytogenes assay is an effective method for the qualitative detection of L. monocytogenes from stainless steel, plastic (polystyrene), and ceramic environmental surface samples.

Highlights
The NEMIS method is the first chemiluminescence detection system based on a novel, patented, dioxetane compound.
MAB21L4 regulates the TGF-β-induced expression of target genes in epidermal keratinocytes
Authors: Ogami Tomohiro , Tamura Yusuke , Toss Kim , Yuki Keiko , Morikawa Masato , Tsutsumi Shuichi , Aburatani Hiroyuki , Miyazawa Keiji , Miyazono Kohei , Koinuma Daizo 
Published: December 2021

Abstract
Smad proteins transduce signals downstream of transforming growth factor-β (TGF-β) and are one of the factors that regulate the expression of genes related to diseases affecting the skin. In the present study, we identified MAB21L4, also known as male abnormal 21 like 4 or C2orf54, as the most up-regulated targets of TGF-β and Smad3 in differentiated human progenitor epidermal keratinocytes using chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq). We found that TGF-β induced expression of the barrier protein involucrin (encoded by the IVL gene). Transcriptional activity of the IVL promoter induced by TGF-β was inhibited by MAB21L4 siRNAs. Further analysis revealed that MAB21L4 siRNAs also down-regulated the expression of several target genes of TGF-β. MAB21L4 protein was located mainly in the cytosol, where it was physically bound to Smad3 and a transcriptional corepressor c-Ski. siRNAs for MAB21L4 did not inhibit the binding of Smad3 to their target genomic regions but down-regulated the acetylation of histone H3 lys 27 (H3K27ac), an active histone mark, near the Smad3 binding regions. These findings suggest that TGF-β-induced MAB21L4 up-regulates the gene expression induced by TGF-β, possibly through the inhibition of c-Ski via physical interaction in the cytosol.