bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dorsal Pigmentation and Its Association with Functional Variation inMC1Rin a Lizard from Different Elevations on the Qinghai–Tibetan Plateau
Authors: Jin Yuanting , Tong Haojie , Shao Gang , Li Jiasheng , Lv Yudie , Wo Yubin , Brown Richard P , Fu Caiyun 
Published: October 2020

AbstractIdentification of the role of the MC1R gene has provided major insights into variation in skin pigmentation in several organisms, including humans, but the evolutionary genetics of this variation is less well established. Variation in this gene and its relationship with degree of melanism was analyzed in one of the world’s highest-elevation lizards, Phrynocephalus theobaldi from the Qinghai–Tibetan Plateau. Individuals from the low-elevation group were shown to have darker dorsal pigmentation than individuals from a high-elevation group. The existence of climatic variation across these elevations was quantified, with lower elevations exhibiting higher air pressure, temperatures, and humidity, but less wind and insolation. Analysis of the MC1R gene in 214 individuals revealed amino acid differences at five sites between intraspecific sister lineages from different elevations, with two sites showing distinct fixed residues at low elevations. Three of the four single-nucleotide polymorphisms that underpinned these amino acid differences were highly significant outliers, relative to the generalized MC1R population structuring, suggestive of selection. Transfection of cells with an MC1R allele from a lighter high-elevation population caused a 43% reduction in agonist-induced cyclic AMP accumulation, and hence lowered melanin synthesis, relative to transfection with an allele from a darker low-elevation population. The high-elevation allele led to less efficient integration of the MC1R protein into melanocyte membranes. Our study identifies variation in the degree of melanism that can be explained by four or fewer MC1R substitutions. We establish a functional link between these substitutions and melanin synthesis and demonstrate elevation-associated shifts in their frequencies.
Interpreting k-mer–based signatures for antibiotic resistance prediction
Authors: Jaillard Magali , Palmieri Mattia , van Belkum Alex , Mahé Pierre 
Published: October 2020

Abstract

Background
Recent years have witnessed the development of several k-mer–based approaches aiming to predict phenotypic traits of bacteria on the basis of their whole-genome sequences. While often convincing in terms of predictive performance, the underlying models are in general not straightforward to interpret, the interplay between the actual genetic determinant and its translation as k-mers being generally hard to decipher.

Results
We propose a simple and computationally efficient strategy allowing one to cope with the high correlation inherent to k-mer–based representations in supervised machine learning models, leading to concise and easily interpretable signatures. We demonstrate the benefit of this approach on the task of predicting the antibiotic resistance profile of a Klebsiella pneumoniae strain from its genome, where our method leads to signatures defined as weighted linear combinations of genetic elements that can easily be identified as genuine antibiotic resistance determinants, with state-of-the-art predictive performance.

Conclusions
By enhancing the interpretability of genomic k-mer–based antibiotic resistance prediction models, our approach improves their clinical utility and hence will facilitate their adoption in routine diagnostics by clinicians and microbiologists. While antibiotic resistance was the motivating application, the method is generic and can be transposed to any other bacterial trait. An R package implementing our method is available at https://gitlab.com/biomerieux-data-science/clustlasso.
Increased Expression of miR-487b Is Associated With Poor Prognosis and Tumor Progression of HBV-Related Hepatocellular Carcinoma
Authors: Cao Xiangang , Yang Qian , Yu Qing 
Published: October 2020

AbstractBackgroundIncreasing evidence has demonstrated the involvement of microRNAs in the pathogenesis of hepatitis B virus (HBV)–related hepatocellular carcinoma (HCC). The aims of this study were to analyze whether miR-487b can be used as a diagnostic and prognostic biomarker for HBV-related HCC and to explore its effect on the biological function of HCC.MethodsThe expression levels of miR-487b in the serum of all subjects were measured by real-time quantitative fluorescence polymerase chain reaction. The diagnostic value of miR-487b in serum was assessed using the receiver operating characteristic (ROC) curve. The relationship between miR-487b and the clinical data of patients was analyzed using the chi-square test. The prognostic value of miR-487b in HCC was assessed by Cox regression analysis and Kaplan-Meier survival. Moreover, CCK-8 and Transwell assays were performed to investigate the effect of miR-487b on HBV-related HCC function.ResultsOur data indicated that miR-487b in HCC patients was significantly higher than in chronic hepatitis B (CHB) patients and healthy controls. Meanwhile, the ROC curve showed that miR-487b had high specificity and sensitivity in the diagnosis of HBV-related HCC. MiR-487b can significantly distinguish between HCC patients and healthy controls and can differentiate HCC patients from CHB patients. Cox regression analysis showed that miR-487b was an independent risk factor. Overexpression of miR-487b was associated with Tumor Node Metastasis stage stage and Barcelona Clinic Liver Cancer stage in HCC patients. Cell function experiments demonstrated that upregulated miR-487b promoted cell proliferation, migration, and invasion.ConclusionsCombined the results of the current study demonstrate that the upregulation of serum miR-487b may serve as a promising noninvasive diagnostic biomarker for HBV-related HCC.
One Health for neglected tropical diseases
Authors: Laing Gabrielle , Vigilato Marco Antonio Natal , Cleaveland Sarah , Thumbi S M , Blumberg Lucille , Salahuddin Naseem , Abela-Ridder Bernadette , Harrison Wendy 
Published: October 2020

Abstract
The forthcoming World Health Organization road map for neglected tropical diseases (NTDs) 2021–2030 recognises the complexity surrounding control and elimination of these 20 diseases of poverty. It emphasises the need for a paradigm shift from disease-specific interventions to holistic cross-cutting approaches coordinating with adjacent disciplines. The One Health approach exemplifies this shift, extending beyond a conventional model of zoonotic disease control to consider the interactions of human and animal health systems within their shared environment and the wider social and economic context. This approach can also promote sustainability and resilience within these systems. To achieve the global ambition on NTD elimination and control, political will, along with contextualised innovative scientific strategies, is required.
Quaternary range dynamics and taxonomy of the Mediterranean collared dwarf racer,Platyceps collaris(Squamata: Colubridae)
Authors: Šmíd Jiří , Aghová Tatiana , Velenská Doubravka , Moravec Jiří , Balej Petr , Naumov Borislav , Popgeorgiev Georgi , Üzüm Nazan , Avci Aziz , Jablonski Daniel 
Published: October 2020

AbstractThe geological and geographical settings of the Eastern Mediterranean have resulted in complex patterns of intraspecific diversifications and phylogeographical histories that can be observed in squamates. In this study, we examined genetic differentiation of the Collared dwarf racer (Platyceps collaris) using a multilocus genetic dataset with a sampling that covered the entire range of the species. We developed distribution models in current and past climatic conditions to assess the dynamics of the species distribution through time. We sequenced a fragment of the cytochrome b mitochondrial gene of the holotype and eight paratypes of Coluber rubriceps thracius, which is considered a synonym of Platyceps collaris. Our results show that there are two distinct clades within P. collaris, one occupying the Balkans and western and southern Anatolia (termed the Balkan–Anatolian clade), the other in the Levant (termed the Levantine clade). All type specimens of C. r. thracius are genetically identical and cluster within the Balkan–Anatolian clade. Distribution models indicate the presence of two refugia during climatically challenging periods. One was in western Anatolia and served as a source for the colonization of the Balkans and southern Anatolia, and the other was in the northern Levant, from where P. collaris dispersed further south. According to our results, we revise the subspecific taxonomy of P. collaris.
Epidemiology of Autoimmune Hepatitis (AIH) in the United States Between 2014 and 2019
Authors: Tunio Nahel A. , Mansoor Emad , Sheriff Mohammed Z. , Cooper Gregory S. , Sclair Seth N. , Cohen Stanley M. 
Published: October 2020

Background and Aims:
Autoimmune hepatitis (AIH) is a chronic, inflammatory disease of the liver with increasing prevalence. However, limited epidemiological data exist for the prevalence of AIH in the United States. We used a large database to describe the prevalence of AIH in the United States and the autoimmune diseases associated with it.

Approach and Results:
Data was collected from a commercial database (Explorys Inc., Cleveland, OH), an aggregate of Electronic Health Record data from 26 major integrated health care systems in the United States. We identified a cohort of patients with a diagnosis of AIH from April 2014 to April 2019 based on a Systemized Nomenclature of Medicine—Clinical Terms and calculated the prevalence of AIH. Of the 37,161,280 individuals active in the database from April 2014 to 2019, we identified 11,600 individuals with a diagnosis of AIH with an overall prevalence rate of 31.2/100,000. The prevalence of AIH was increased in females compared with males [odds ratio (OR)=3.21, P<0.0001], elderly (aged above 65 y) compared with adults (aged 18 to 65 y) and children (aged below 18 y) (OR=2.51, P<0.0001) and whites compared with African Americans, Asians, and Hispanics (OR=1.12, P<0.0001). Moreover, patients with AIH were more likely to have Sjögren syndrome, systemic lupus erythematosus, ulcerative colitis, celiac disease, rheumatoid arthritis, Crohn’s disease, and autoimmune thyroiditis as compared with patients without AIH.

Conclusions:
We found that the estimated prevalence of AIH in the United States is 31.2/100,000, which is comparable to the reported prevalence of AIH in Europe. We confirmed that AIH has a strong association with other autoimmune diseases studied in the literature.
The Correlative Factors and Probable Mechanism of Epidural Fluid Collection After Cranioplasty
Authors: Zhang Shangming , Li Songyuan , Wei Liangfeng , Chen Hongjie , Wang Shousen , Wang Wei 
Published: October 2020

Objective:
Epidural fluid collection (EFC) is one of the postoperative complications of cranioplasty and is easily ignored. Not only the predictive factors of EFC formation are unknown, the pathologic mechanisms are also unknown. We determined to analyze the predictive factors and the mechanism of EFC formation.

Methods:
A total of 340 patients underwent cranioplasty were retrospectively analyzed in this study. A series of factors were compared in the EFC and none-EFC groups and farther compared in the progress epidural fluid collection (PEFC) and none-PEFC subgroups to determine the predictive factors. The t test, χ
2 test, and logistic regression analysis were used in statistical analysis.

Results:
The rate of EFC formation was 34.41%, and the size of skull defect, preoperative volume of collapse, intraoperative dura suspending, a pre- or intraoperative ventriculoperitoneal shunt (V-P shunt), and an postoperative air bubble in epidural space were predictive factors for EFC formation. Furthermore, the incidence of PEFC was 10.29%, the size of skull defects and intraoperative dura suspending were predictive factors for PEFC formation. The protein ratio and lactate dehydrogenase (LDH) ratio of effusion to serum were >0.5 and 0.6, respectively. There was no adverse prognosis.

Conclusions:
Although EFC can be treated with conservative therapy, we need to emphasize EFC incidence and development. As neurosurgeons, it is necessary to analyze the preoperative predictive factors of EFC, pay attention to the intraoperative details such as dura suspending to prevent PEFC formation, and the early intervention should be performed in the postoperative.
Perioperative Nonsteroidal Anti-inflammatory Drugs (NSAID) Administration and Acute Kidney Injury (AKI) in Major Gastrointestinal Surgery
Authors:   STARSurg Collaborative
Published: October 2020

Objective:
This study aimed to determine the relationship between early postoperative nonsteroidal anti-inflammatory drug (NSAID) administration and postoperative acute kidney injury (AKI) and anastomotic leak.

Summary Background Data:
NSAIDs have analgesic, opioid-sparing, and anti-inflammatory effects. However, their postoperative use is limited by concerns around increased risk of AKI and anastomotic leak.

Methods:
A secondary analysis of a multicenter, prospective cohort study including patients undergoing elective or emergency major gastrointestinal surgery from September to December 2015 across 173 hospitals in the United Kingdom and ireland. Exposure to early postoperative NSAIDs was defined as NSAID administration on postoperative days 0 to 3. The primary outcome was the 7-day postoperative AKI rate. Propensity score matching was used to balance treatment groups and estimate treatment effects that are presented as odds ratios, alongside the corresponding 95% confidence interval (CI).

Results:
Overall 19.8% (1039/5240) of patients received early NSAIDs. AKI rates were 10.6% in the early NSAID group and 14.9% in the no NSAID group. The anastomotic leak rate in patients who received an anastomosis was 4.8% in the NSAIDs group and 6.0% in the no NSAIDs group. Following propensity score matching, early use of NSAIDs was not significantly associated with AKI (adjusted odds ratio 0.80, 95% CI 0.63–1.00, P = 0.057). This finding was consistent in subgroup analyses by NSAID dosage and timing. In patients who had a gastrointestinal anastomosis, NSAIDs were not associated with anastomotic leak (adjusted odds ratio 0.85, 95% CI 0.58–1.21, P = 0.382).

Conclusions:
Administration of NSAIDs in the early postoperative period is safe in selected patients following major gastrointestinal surgery.
On operator semigroups arising in the study of incompressible viscous fluid flows
Authors: Hieber Matthias 
Published: October 2020

This article concentrates on various operator semigroups arising in the study of viscous and incompressible flows. Of particular concern are the classical Stokes semigroup, the hydrostatic Stokes semigroup, the Oldroyd as well as the Ericksen–Leslie semigroup. Besides their intrinsic interest, the properties of these semigroups play an important role in the investigation of the associated nonlinear equations.
This article is part of the theme issue ‘Semigroup applications everywhere’.
Maximal inequalities for stochastic convolutions in 2-smooth Banach spaces and applications to stochastic evolution equations
Authors: van Neerven Jan , Veraar Mark 
Published: October 2020

This paper presents a survey of maximal inequalities for stochastic convolutions in 2-smooth Banach spaces and their applications to stochastic evolution equations.This article is part of the theme issue ‘Semigroup applications everywhere’.
Prenatal Environmental Stressors Impair Postnatal Microglia Function and Adult Behavior in Males
Authors: Block Carina L. , Eroglu Oznur , Mague Stephen D. , Sriworarat Chaichontat , Blount Cameron , Malacon Karen E. , Beben Kathleen A. , Ndubuizu Nkemdilim , Talbot Austin , Gallagher Neil M. , Jo Young Chan , Nyangacha Timothy , Carlson David E. , Dzirasa Kafui , Eroglu Cagla , Bilbo Staci D. 
Published: October 2020

AbstractGestational exposure to environmental toxins and socioeconomic stressors are epidemiologically linked to neurodevelopmental disorders with strong male-bias, such as autism. We modeled these prenatal risk factors in mice, by co-exposing pregnant dams to an environmental pollutant and limited-resource stress, which robustly activated the maternal immune system. Only male offspring displayed long-lasting behavioral abnormalities and alterations in the activity of brain networks encoding social interactions. Cellularly, prenatal stressors diminished microglial function within the anterior cingulate cortex, a central node of the social coding network, in males during early postnatal development. Genetic ablation of microglia during the same critical period mimicked the impact of prenatal stressors on a male-specific behavior, indicating that environmental stressors alter neural circuit formation in males via impairing microglia function during development.
Early induction of SARS-CoV-2 specific T cells associates with rapid viral clearance and mild disease in COVID-19 patients
Authors: Tan Anthony T. , Linster Martin , Tan Chee Wah , Le Bert Nina , Chia Wan Ni , Kunasegaran Kamini , Zhuang Yan , Tham Christine Y. L. , Chia Adeline , Smith Gavin J. , Young Barnaby , Kalimuddin Shirin , Low Jenny G. H. , Lye David , Wang Lin-Fa , Bertoletti Antonio 
Published: October 2020

SummaryVirus-specific humoral and cellular immunity act synergistically to protect the host from viral infection. We interrogated the dynamic changes of virological and immunological parameters in 12 patients with symptomatic acute SARS-CoV-2 infection from disease onset to convalescence or death. We quantified SARS-CoV-2 viral RNA in the respiratory tract in parallel with antibodies and circulating T cells specific for various structural (NP, M, ORF3a and spike) and non-structural proteins (ORF7/8, NSP7 and NSP13). We observed that while rapid induction and quantity of humoral responses were associated with increased disease severity, an early induction of SARS-CoV-2 specific T cells was present in patients with mild disease and accelerated viral clearance. These findings provide further support for a protective role of SARS-CoV-2 specific T cells over antibodies during SARS-CoV-2 infection with important implications in vaccine design and immune-monitoring.
A drug-screening platform based on organotypic cultures identifies vulnerabilities to prevent local relapse and treat established brain metastasis
Authors: Zhu Lucía , Yebra Natalia , Retana Diana , Miarka Lauritz , Hernández-Encinas Elena , Blanco-Aparicio Carmen , Martínez Sonia , Soffietti Riccardo , Bertero Luca , Cassoni Paola , Weiss Tobias , Muñoz Javier , Sepúlveda Juan Manuel , Pérez-Núñez Ángel , Hernández-Laín Aurelio , Ruano Yolanda , Toldos Oscar , Caleiras Eduardo , Megías Diego , Graña-Castro Osvaldo , Nör Carolina , Taylor Michael D. , Cussó Lorena , Desco Manuel , Weller Michael , Pastor Joaquín , Valiente Manuel 
Published: October 2020

AbstractExclusion of brain metastases from clinical trials is a major cause of the limited therapeutic options for this growing population of cancer patients. Here, we report a medium-throughput drug-screening platform (METPlatform) based on organotypic cultures that allows to evaluate inhibitors against metastases growingin situ. By applying this approach to brain metastasis, we identified several hits from a library of FDA approved inhibitors and others being tested in clinical trials. A blood-brain barrier permeable HSP90 inhibitor showed high potency against mouse and human brain metastases at clinically relevant stages of the disease, including a novel model of local relapse after neurosurgery. Furthermore,in situproteomic analysis applied to organotypic cultures with metastases treated with the chaperone inhibitor revealed novel biomarkers in human brain metastasis and actionable mechanisms of resistance. Our work validates METPlatform as a potent resource for metastasis research integrating drug-screening and unbiased omic approaches that is fully compatible with human samples. We envision that METPlatform could be established as a clinically relevant strategy to personalize the management of metastatic disease in the brain and elsewhere.SummarySystemic spread of cancer continues to be the key aspect associated with lethality. In this publication, Zhu et al. describes a drug-screening platform specifically designed to study vulnerabilities of metastasis when colonizing secondary organs and demonstrates its value in difficult-to-treat brain metastasis using new models and patient-derived samples.
Infertility due to defective sperm flagella caused by an intronic deletion in DNAH17 that perturbs splicing
Authors: Nosková Adéla , Hiltpold Maya , Janett Fredi , Echtermann Thomas , Fang Zih-Hua , Sidler Xaver , Selige Christin , Hofer Andreas , Neuenschwander Stefan , Pausch Hubert 
Published: October 2020

ABSTRACTArtificial insemination in pig (Sus scrofa domesticus) breeding involves the evaluation of the semen quality of breeding boars. Ejaculates that fulfill predefined quality requirements are processed, diluted and used for inseminations. Within short time, eight Swiss Large White boars producing immotile sperm that had multiple morphological abnormalities of the sperm flagella were noticed at a semen collection center. The eight boars were inbred on a common ancestor suggesting that the novel sperm flagella defect is a recessive trait. Transmission electron microscopy cross-sections revealed that the immotile sperm had disorganized flagellar axonemes. Haplotype-based association testing involving microarray-derived genotypes at 41,094 SNPs of six affected and 100 fertile boars yielded strong association (P=4.22 × 10−15) at chromosome 12. Autozygosity mapping enabled us to pinpoint the causal mutation on a 1.11 Mb haplotype located between 3,473,632 and 4,587,759 bp. The haplotype carries an intronic 13-bp deletion (Chr12:3,556,401-3,556,414 bp) that is compatible with recessive inheritance. The 13-bp deletion excises the polypyrimidine tract upstream exon 56 ofDNAH17(XM_021066525.1:c.8510-17_8510-5del) encoding dynein axonemal heavy chain 17. Transcriptome analysis of the testis of two affected boars revealed that the loss of the polypyrimidine tract causes exon skipping which results in the in-frame loss of 89 amino acids from DNAH17. Disruption of DNAH17 impairs the assembly of the flagellar axoneme and manifests in multiple morphological abnormalities of the sperm flagella. Direct gene testing may now be implemented to monitor the defective allele in the Swiss Large White population and prevent the frequent manifestation of a sterilizing sperm tail disorder in breeding boars.
Loss of MGA mediated Polycomb repression promotes tumor progression and invasiveness
Authors: Mathsyaraja Haritha , Catchpole Jonathen , Eastwood Emily , Babaeva Ekaterina , Geuenich Michael , Cheng Pei Feng , Freie Brian , Ayers Jessica , Yu Ming , Wu Nan , Poudel Kumud R , Koehne Amanda , Grady William , Houghton A McGarry , Shiio Yuzuru , MacPherson David P , Eisenman Robert N 
Published: October 2020

ABSTRACTMGA, a transcription factor and member of the MYC network, is mutated or deleted in a broad spectrum of malignancies. As a critical test of a tumor suppressive role, we inactivated Mga in two mouse models of non-small cell lung cancer using a CRISPR based approach. MGA loss significantly accelerated tumor growth in both models and led to de-repression of atypical Polycomb PRC1.6, E2F and MYC-MAX targets. Similarly, MGA depletion in human lung adenocarcinoma lines augmented invasive capabilities. We further show that MGA, E2F6 and L3MBTL2 co-occupy thousands of promoters and that MGA stabilizes PRC1.6 subunits. Lastly, we report that MGA loss has also a pro-growth effect in human colon organoids. Our studies establish MGA as a bona fide tumor suppressor in vivo and suggest a tumor suppressive mechanism in adenocarcinomas resulting from widespread transcriptional attenuation of MYC and E2F targets mediated by an atypical Polycomb complex containing MGA-MAX dimers.