bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of group size and reproductive status on faecal glucocorticoid concentration and vigilance in a free-ranging population of Przewalski’s gazelle
Authors: Liu Ruoshuang , Shi Jianbin , Liu Dingzhen , Dong Shikui , Zhang Yu , Wu Yonglin , Guo Dongsheng 
Published: March 2020

AbstractElevated glucocorticoid (GC) concentration and increased vigilance are two common responses to predation risk in mammals. Chronic high-level GC concentration and vigilance occur at the expense of other life maintenance and reproduction activities, reflecting a trade-off between individual survival and future fecundity. Przewalski’s gazelle (Procapra przewalskii) is a group-living ungulate endemic to the high-altitude Qinghai Lake region of China. Group-size effect on gazelle vigilance has been examined, yet little is known about how their GC concentration is affected by group size or reproductive status. In this study, we examined the effect of group size and reproductive status on faecal glucocorticoid metabolite (FGM) concentrations and individual vigilance during different stages of the reproduction cycle (i.e. non-breeding, lambing and rutting) in free-ranging adult female Przewalski’s gazelles. Group size did not influence FGMs significantly, but mean vigilance duration increased with group size. The gazelles’ FGMs and vigilance peaked in lambing season. FGMs showed no difference between rutting season and non-reproductive season, but vigilance was lowest in the rutting season. FGMs correlated with vigilance frequency and vigilance duration. Antipredator responses of female Przewalski’s gazelles appear to change with reproductive status but not with group size in free-ranging females. Management measures should be taken in the lambing season to minimize stress on mother gazelles.
Sectm1a deficiency aggravates inflammation-triggered cardiac dysfunction through disruption of LXRα signalling in macrophages
Authors: Li Yutian , Deng Shan , Wang Xiaohong , Huang Wei , Chen Jing , Robbins Nathan , Mu Xingjiang , Essandoh Kobina , Peng Tianqing , Jegga Anil G , Rubinstein Jack , Adams David E , Wang Yigang , Peng Jiangtong , Fan Guo-Chang 
Published: March 2020

Abstract

Aims
Cardiac dysfunction is a prevalent comorbidity of disrupted inflammatory homeostasis observed in conditions such as sepsis (acute) or obesity (chronic). Secreted and transmembrane protein 1a (Sectm1a) has previously been implicated to regulate inflammatory responses, yet its role in inflammation-associated cardiac dysfunction is virtually unknown.

Methods and results
Using the CRISPR/Cas9 system, we generated a global Sectm1a-knockout (KO) mouse model and observed significantly increased mortality and cardiac injury after lipopolysaccharide (LPS) injection, when compared with wild-type (WT) control. Further analysis revealed significantly increased accumulation of inflammatory macrophages in hearts of LPS-treated KO mice. Accordingly, ablation of Sectm1a remarkably increased inflammatory cytokines levels both in vitro [from bone marrow-derived macrophages (BMDMs)] and in vivo (in serum and myocardium) after LPS challenge. RNA-sequencing results and bioinformatics analyses showed that the most significantly down-regulated genes in KO-BMDMs were modulated by LXRα, a nuclear receptor with robust anti-inflammatory activity in macrophages. Indeed, we identified that the nuclear translocation of LXRα was disrupted in KO-BMDMs when treated with GW3965 (LXR agonist), resulting in higher levels of inflammatory cytokines, compared to GW3965-treated WT-cells. Furthermore, using chronic inflammation model of high-fat diet (HFD) feeding, we observed that infiltration of inflammatory monocytes/macrophages into KO-hearts were greatly increased and accordingly, worsened cardiac function, compared to WT-HFD controls.

Conclusion
This study defines Sectm1a as a new regulator of inflammatory-induced cardiac dysfunction through modulation of LXRα signalling in macrophages. Our data suggest that augmenting Sectm1a activity may be a potential therapeutic approach to resolve inflammation and associated cardiac dysfunction.
UPCLASS: a deep learning-based classifier for UniProtKB entry publications
Authors: Teodoro Douglas , Knafou Julien , Naderi Nona , Pasche Emilie , Gobeill Julien , Arighi Cecilia N , Ruch Patrick 
Published: March 2020

Abstract
In the UniProt Knowledgebase (UniProtKB), publications providing evidence for a specific protein annotation entry are organized across different categories, such as function, interaction and expression, based on the type of data they contain. To provide a systematic way of categorizing computationally mapped bibliographies in UniProt, we investigate a convolutional neural network (CNN) model to classify publications with accession annotations according to UniProtKB categories. The main challenge of categorizing publications at the accession annotation level is that the same publication can be annotated with multiple proteins and thus be associated with different category sets according to the evidence provided for the protein. We propose a model that divides the document into parts containing and not containing evidence for the protein annotation. Then, we use these parts to create different feature sets for each accession and feed them to separate layers of the network. The CNN model achieved a micro F1-score of 0.72 and a macro F1-score of 0.62, outperforming baseline models based on logistic regression and support vector machine by up to 22 and 18 percentage points, respectively. We believe that such an approach could be used to systematically categorize the computationally mapped bibliography in UniProtKB, which represents a significant set of the publications, and help curators to decide whether a publication is relevant for further curation for a protein accession.
Database URL: https://goldorak.hesge.ch/bioexpclass/upclass/.
Pyoderma gangrenosum complicating a permanent pacemaker implantation: a case report and literature review
Authors: Frey Pierre , Akret Chrystelle , Irles Didier , Dompnier Antoine , Bing Anne-Claire 
Published: March 2020

Abstract

Background
Pocket complications are common after cardiac implantable electronic device implantation. We report a rare case of pyoderma gangrenosum (PG) complicating a permanent pacemaker implantation, and the first literature review of 10 published cases.

Case summary
Five days after pacemaker implantation for heart failure and 2:1 atrioventricular block, a 93-year-old man had pain in the scar and bleeding on contact. Two days later, he had fever, inflammatory syndrome, and a necrotic 7-cm wound. The pacemaker was removed and he was started on antibiotics. Due to a lack of bacterial growth in samples, PG (a rare aseptic, destructive inflammatory cutaneous condition) was suspected, and histology was compatible with this diagnosis. High-dose corticosteroids vastly improved his condition within 1 week, and after 2 months of decreasing-dose corticosteroid therapy, complete healing and normalization of the inflammatory syndrome were observed.

Discussion
Pyoderma gangrenosum should be considered if there is aseptic skin ulceration that is not controlled by antibiotic treatment. The first-line treatment for PG is high-dose systemic corticosteroids.
Receiving care according to national heart failure guidelines is associated with lower total costs: an observational study in Region Halland, Sweden
Authors: Yasin Zayed M , Anderson Philip D , Lingman Markus , Kwatra Japneet , Ashfaq Awais , Slutzman Jonathan E , Agvall Björn 
Published: March 2020

Abstract

Aims
Patients with heart failure (HF) have high costs, morbidity, and mortality, but it is not known if appropriate pharmacotherapy (AP), defined as compliance with international evidence-based guidelines, is associated with improved costs and outcomes. The purpose of this study was to evaluate HF patients’ health care utilization, cost and outcomes in Region Halland (RH), Sweden, and if AP was associated with lower costs.

Methods and results
A total of 5987 residents of RH in 2016 carried HF diagnoses. Costs were assigned to all health care utilization (inpatient, outpatient, emergency department, primary health care, and medications) using a Patient Encounter Costing methodology. Care of HF patients cost €58.6 M, (€9790/patient) representing 8.7% of RH’s total visit expenses and 14.9% of inpatient care (IPC) expenses. Inpatient care represented 57.2% of this expenditure, totalling €33.5 M (€5601/patient). Receiving AP was associated with significantly lower costs, by €1130 per patient (P &lt; 0.001, 95% confidence interval 574–1687). Comorbidities such as renal failure, diabetes, chronic obstructive pulmonary disease, and cancer were significantly associated with higher costs.

Conclusion
Heart failure patients are heavy users of health care, particularly IPC. Receiving AP is associated with lower costs even adjusting for comorbidities, although causality cannot be proven from an observational study. There may be an opportunity to decrease overall costs and improve outcomes by improving prescribing patterns and associated high-quality care.
An image dataset related to automated macrophage detection in immunostained lymphoma tissue samples
Authors: Wagner Marcus , Reinke Sarah , Hänsel René , Klapper Wolfram , Braumann Ulf-Dietrich 
Published: March 2020

Abstract

Background
We present an image dataset related to automated segmentation and counting of macrophages in diffuse large B-cell lymphoma (DLBCL) tissue sections. For the classification of DLBCL subtypes, as well as for providing a prognosis of the clinical outcome, the analysis of the tumor microenvironment and, particularly, of the different types and functions of tumor-associated macrophages is indispensable. Until now, however, most information about macrophages has been obtained either in a completely indirect way by gene expression profiling or by manual counts in immunohistochemically (IHC) fluorescence-stained tissue samples while automated recognition of single IHC stained macrophages remains a difficult task. In an accompanying publication, a reliable approach to this problem has been established, and a large set of related images has been generated and analyzed.

Results
Provided image data comprise (i) fluorescence microscopy images of 44 multiple immunohistostained DLBCL tumor subregions, captured at 4 channels corresponding to CD14, CD163, Pax5, and DAPI; (ii) ”cartoon-like” total variation–filtered versions of these images, generated by Rudin-Osher-Fatemi denoising; (iii) an automatically generated mask of the evaluation subregion, based on information from the DAPI channel; and (iv) automatically generated segmentation masks for macrophages (using information from CD14 and CD163 channels), B-cells (using information from Pax5 channel), and all cell nuclei (using information from DAPI channel).

Conclusions
A large set of IHC stained DLBCL specimens is provided together with segmentation masks for different cell populations generated by a reference method for automated image analysis, thus featuring considerable reuse potential.
Engaging citizen scientists to build healthy park environments in Colombia
Authors: Rubio María Alejandra , Triana Camilo , King Abby C , Rosas Lisa G , Banchoff Ann W , Rubiano Oscar , Chrisinger Benjamin W , Sarmiento Olga L 
Published: March 2020

Abstract
Colombia’s Recreovía program offers community-based free physical activity (PA) classes in parks. We evaluated built and social environmental factors influencing Recreovía local park environments, and facilitated a consensus-building and advocacy process among community members, policymakers and academic researchers aimed at improving uptake and impact of the Recreovía program. We used a mixed-methods approach, with individual and contextual PA measurements and a resident-enabled participatory approach (the Our Voice citizen science engagement model). Recreovía participants were likely to be women meeting PA recommendations, and highly satisfied with the Recreovía classes. Reported facilitators of the Recreovía included its role in enhancing social and individual well-being through PA classes. Reported barriers to usage were related to park maintenance, cleanliness and safety. The Our Voice process elicited community reflection, empowerment, advocacy and action. Our Voice facilitated the interplay among stakeholders and community members to optimize the Recreovía program as a facilitator of active living, and to make park environments more welcoming.
A missense variant in specificity protein 6 (SP6) is associated with amelogenesis imperfecta
Authors: Smith Claire E L , Whitehouse Laura L E , Poulter James A , Wilkinson Hewitt Laura , Nadat Fatima , Jackson Brian R , Manfield Iain W , Edwards Thomas A , Rodd Helen D , Inglehearn Chris F , Mighell Alan J 
Published: March 2020

Abstract
Amelogenesis is the process of enamel formation. For amelogenesis to proceed, the cells of the inner enamel epithelium (IEE) must first proliferate and then differentiate into the enamel-producing ameloblasts. Amelogenesis imperfecta (AI) is a heterogeneous group of genetic conditions that result in defective or absent tooth enamel. We identified a 2 bp variant c.817_818GC&gt;AA in SP6, the gene encoding the SP6 transcription factor, in a Caucasian family with autosomal dominant hypoplastic AI. The resulting missense protein change, p.(Ala273Lys), is predicted to alter a DNA-binding residue in the first of three zinc fingers. SP6 has been shown to be crucial to both proliferation of the IEE and to its differentiation into ameloblasts. SP6 has also been implicated as an AI candidate gene through its study in rodent models. We investigated the effect of the missense variant in SP6 (p.(Ala273Lys)) using surface plasmon resonance protein-DNA binding studies. We identified a potential SP6 binding motif in the AMBN proximal promoter sequence and showed that wild-type (WT) SP6 binds more strongly to it than the mutant protein. We hypothesize that SP6 variants may be a very rare cause of AI due to the critical roles of SP6 in development and that the relatively mild effect of the missense variant identified in this study is sufficient to affect amelogenesis causing AI, but not so severe as to be incompatible with life. We suggest that current AI cohorts, both with autosomal recessive and dominant disease, be screened for SP6 variants.
Postnatal Ethanol Exposure Activates HDAC-Mediated Histone Deacetylation, Impairs Synaptic Plasticity Gene Expression and Behavior in Mice
Authors: Shivakumar Madhu , Subbanna Shivakumar , Joshi Vikram , Basavarajappa Balapal S 
Published: March 2020

Abstract

Background
Alcohol consumption during pregnancy is widespread and contributes to pediatric neurological defects, including hippocampal and neocortex dysfunction, causing cognitive deficits termed fetal alcohol spectrum disorders. However, the critical mechanisms underlying these brain abnormalities remain poorly described.

Methods
Using a postnatal ethanol exposure (PEE) animal model and pharmacological, epigenetic, synaptic plasticity-related and behavioral approaches, we discovered a novel persistent epigenetic mechanism of neurodegeneration in neonatal hippocampus and neocortex brain regions and of cognitive decline in adult animals.

Results
PEE, which activates caspase-3 (CC3, a neurodegeneration marker), enhanced histone deacetylase (HDAC1–HDAC3) levels and reduced histone 3 (H3) and 4 (H4) acetylation (ac) in mature neurons. PEE repressed the expression of several synaptic plasticity genes, such as brain-derived neurotrophic factor, C-Fos, early growth response 1 (Egr1), and activity-regulated cytoskeleton-associated protein (Arc). Detailed studies on Egr1 and Arc expression revealed HDAC enrichment at their promoter regions. HDAC inhibition with trichostatin A (TSA) before PEE rescued H3ac/H4ac levels and prevented CC3 formation. Antagonism/null mutation of cannabinoid receptor type-1 (CB1R) before PEE to inhibit CC3 production prevented Egr1 and Arc loss via epigenetic events. TSA administration before PEE prevented postnatal ethanol-induced loss of Egr1 and Arc expression and neurobehavioral defects in adult mice via epigenetic remodeling. In adult mice, 3-day TSA administration attenuated PEE-induced behavioral defects.

Conclusions
These findings demonstrate that CB1R/HDAC-mediated epigenetic remodeling disrupts gene expression and is a critical step in fetal alcohol spectrum disorder-associated cognitive decline but is reversed by restoration of histone acetylation in the brain.
Responding to Outbreaks of Human Immunodeficiency Virus Among Persons Who Inject Drugs—United States, 2016–2019: Perspectives on Recent Experience and Lessons Learned
Authors: Lyss Sheryl B , Buchacz Kate , McClung R Paul , Asher Alice , Oster Alexandra M 
Published: March 2020

Abstract
In 2015, a large human immunodeficiency virus (HIV) outbreak occurred among persons who inject drugs (PWID) in Indiana. During 2016–2019, additional outbreaks among PWID occurred across the United States. Based on information disseminated by responding health departments and Centers for Disease Control and Prevention (CDC) involvement, we offer perspectives about characteristics of and public health responses to 6 such outbreaks. Across outbreaks, injection of opioids (including fentanyl) or methamphetamine predominated; many PWID concurrently used opioids and methamphetamine or cocaine. Commonalities included homelessness or unstable housing, previous incarceration, and hepatitis C virus exposure. All outbreaks occurred in metropolitan areas, including some with substantial harm reduction and medical programs targeted to PWID. Health departments experienced challenges locating case patients and contacts, linking and retaining persons in care, building support to strengthen harm-reduction programs, and leveraging resources. Expanding the concept of vulnerability to HIV outbreaks and other lessons learned can be considered for preventing, detecting, and responding to future outbreaks among PWID.
The spectrum of macrophage activation by immunometabolism
Authors: Kang Sujin , Kumanogoh Atsushi 
Published: March 2020

Abstract
Macrophages are heterogeneous and plastic, and play several diverse functions in immune responses. Emerging data provide evidence of multiple roles for metabolic pathways in the control of macrophage effector functions. The diverse functions of macrophages are categorized into two main subsets: classical activated macrophages (M1) and alternative activated macrophages (M2). M1 macrophages secrete pro-inflammatory cytokines and reactive oxygen species and migrate into inflamed sites as a part of host defenses. On the other hand, M2 macrophages are involved in immune homeostasis by producing anti-inflammatory cytokines and phagocytosing apoptotic cells. Metabolic reprogramming of environmental or cellular nutrients such as glucose, lipids and amino acids supports this diversity. Mechanistically, the mammalian target of rapamycin (mTOR) network plays important roles in the effector functions of macrophages by modulating cellular metabolism and regulating gene expression at the transcriptional and translational levels. In this review, we outline immunometabolism and provide insights into metabolic regulation by mTOR in macrophages.
The Politics of Data Access in Studying Violence across Methodological Boundaries: What We Can Learn from Each Other?
Authors: Brigden Noelle K , Gohdes Anita R 
Published: March 2020

AbstractIn this article, we investigate where the ethics of data collection and access of two widely disparate methodological approaches studying violence intersect, and we explore how these respective intellectual communities can learn from each other. We compare and contrast the research strategies and dilemmas confronted by researchers using quantitative methods to collect and analyze “big data” and those by researchers conducting interpretivist ethnography grounded in the method of participant observation. The shared context of participant vulnerability produces overlapping concerns about our work. With shifts in quantitative conflict research to examine the microdynamics of violence, quandaries of confidentiality and the ethics of exposure have become increasingly salient. At the same time, ethical dilemmas that arise in the large-scale collection of data offer important points of reflection regarding the ethics of participant observation as it is performed in ethnographic research. Instead of focusing on areas of disagreement, we suggest that interpretivist fieldworkers and quantitative researchers can learn from how the politics of information materialize across divergent research methods.
High-priority drug-drug interaction clinical decision support overrides in a newly implemented commercial computerized provider order-entry system: Override appropriateness and adverse drug events
Authors: Edrees Heba , Amato Mary G , Wong Adrian , Seger Diane L , Bates David W 
Published: March 2020

Abstract

Objective
The study sought to determine frequency and appropriateness of overrides of high-priority drug-drug interaction (DDI) alerts and whether adverse drug events (ADEs) were associated with overrides in a newly implemented electronic health record.

Materials and Methods
We conducted a retrospective study of overridden high-priority DDI alerts occurring from April 1, 2016, to March 31, 2017, from inpatient and outpatient settings at an academic health center. We studied highest-severity DDIs that were previously designated as “hard stops” and additional high-priority DDIs identified from clinical experience and literature review. All highest-severity alert overrides (n = 193) plus a stratified random sample of additional overrides (n = 371) were evaluated for override appropriateness, using predetermined criteria. Charts were reviewed to identify ADEs for overrides that resulted in medication administration. A chi-square test was used to compare ADE rate by override appropriateness.

Results
Of 16 011 alerts presented to providers, 15 318 (95.7%) were overridden, including 193 (87.3%) of the highest-severity DDIs and 15 125 (95.8%) of additional DDIs. Override appropriateness was 45.4% overall, 0.5% for highest-severity DDIs and 68.7% for additional DDIs. For alerts that resulted in medication administration (n = 423, 75.0%), 29 ADEs were identified (6.9%, 5.1 per 100 overrides). The rate of ADEs was higher with inappropriate vs appropriate overrides (9.4% vs 4.3%; P = .038).

Conclusions
The override rate was nearly 90% for even the highest-severity DDI alerts, indicating that stronger suggestions should be made for these alerts, while other alerts should be evaluated for potential suppression.
Capillary Gas Chromatography/Mass Spectrometry with Chemical Ionization and Negative Ion Detection for Confirmation of Identity of Patulin in Apple Juice
Authors: Roach John A G , White Kevin D , Trucksess Mary W , Thomas Frederick S 
Published: March 2020

Abstract
Gas chromatography/mass spectrometry (GC/MS) with negative ion chemical ionization permits detection of underivatized patulin in apple juice extracts while minimizing co-extractive responses. The technique has been used with a variety of capillary columns in quadrupole, ion trap, and magnetic sector GC/MS instruments to confirm presumptive findings of patulin in apple juice at concentrations ranging from 68 to 3700 μg/L. The demonstrated ability to use any of these 3 mass spectrometers and several capillary columns to confirm the identity of patulin are significant strengths of the technique.