bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolutionary history ofMycobacterium lepraein the Pacific Islands
Authors: Blevins Kelly E. , Crane Adele E. , Lum Christopher , Furuta Kanako , Fox Keolu , Stone Anne C. 
Published: October 2020

As one of the oldest known human diseases, leprosy or Hansen's disease remains a public health concern around the world with over 200 000 new cases in 2018. Most human leprosy cases are caused byMycobacterium leprae, but a small number of cases are now known to be caused byMycobacterium lepromatosis, a sister taxon ofM. leprae. The global pattern of genomic variation inM. lepraeis not well defined. Particularly, in the Pacific Islands, the origins of leprosy are disputed. Historically, it has been argued that leprosy arrived on the islands during nineteenth century colonialism, but some oral traditions and palaeopathological evidence suggest an older introduction. To address this, as well as investigate patterns of pathogen exchange across the Pacific Islands, we extracted DNA from 39 formalin-fixed paraffin-embedded biopsy blocks dating to 1992–2016. Using whole-genome enrichment and next-generation sequencing, we produced nineM. lepraegenomes dating to 1998–2015 and ranging from 4-63× depth of coverage. Phylogenetic analyses indicate that these strains belong to basal lineages within theM. lepraephylogeny, specifically falling in branches 0 and 5. The phylogeographical patterning and evolutionary dating analysis of these strains support a pre-modern introduction ofM. lepraeinto the Pacific Islands.This article is part of the theme issue ‘Insights into health and disease from ancient biomolecules’.
Multi-omic detection ofMycobacterium lepraein archaeological human dental calculus
Authors: Fotakis Anna K. , Denham Sean D. , Mackie Meaghan , Orbegozo Miren Iraeta , Mylopotamitaki Dorothea , Gopalakrishnan Shyam , Sicheritz-Pontén Thomas , Olsen Jesper V. , Cappellini Enrico , Zhang Guojie , Christophersen Axel , Gilbert M. Thomas P. , Vågene Åshild J. 
Published: October 2020

Mineralized dental plaque (calculus) has proven to be an excellent source of ancient biomolecules. Here we present aMycobacterium lepraegenome (6.6-fold), the causative agent of leprosy, recovered via shotgun sequencing of sixteenth-century human dental calculus from an individual from Trondheim, Norway. When phylogenetically placed, this genome falls in branch 3I among the diversity of other contemporary ancient strains from Northern Europe. Moreover, ancient mycobacterial peptides were retrieved via mass spectrometry-based proteomics, further validating the presence of the pathogen.Mycobacterium lepraecan readily be detected in the oral cavity and associated mucosal membranes, which likely contributed to it being incorporated into this individual's dental calculus. This individual showed some possible, but not definitive, evidence of skeletal lesions associated with early-stage leprosy. This study is the first known example of successful multi-omics retrieval ofM. lepraefrom archaeological dental calculus. Furthermore, we offer new insights into dental calculus as an alternative sample source to bones or teeth for detecting and molecularly characterizingM. lepraein individuals from the archaeological record.This article is part of the theme issue ‘Insights into health and disease from ancient biomolecules’.
“Corticosteroid pulses for hospitalized patients with COVID-19: Effects on mortality”
Authors: Cusacovich Ivan , Aparisi Álvaro , Marcos Miguel , Ybarra-Falcón Cristina , Iglesias-Echevarria Carolina , Lopez-Veloso Maria , Barraza-Vengoechea Julio , Dueñas Carlos , Juarros Martínez Santiago Antonio , Rodríguez-Alonso Beatriz , Martín-Oterino José-Ángel , Montero-Baladia Miguel , Moralejo Leticia , Andaluz-Ojeda David , Gonzalez-Fuentes Roberto 
Published: October 2020

ABSTRACTBackground: COVID-19 has high mortality in hospitalized patients, and we need effective treatments. Our objective was to assess corticosteroid pulses’ influence on 60-days mortality in hospitalized patients with severe COVID-19, intensive care admission, and hospital stay. Methods: We designed a multicenter retrospective cohort study in three teaching hospitals of Castilla y León, Spain (865.096 people). We selected patients with confirmed COVID-19 and lung involvement with a pO2/FiO2 < 300, excluding those exposed to immunosuppressors before or during hospitalization, patients terminally ill at admission, or died the first 24 hours. We performed a propensity score matching (PSM) adjusting covariates that modify the probability of being treated. Then we used a Cox regression model in the PSM group to consider factors affecting mortality. Findings: From 2933 patients, 257 fulfilled the inclusion and exclusion criteria. One hundred and twenty-four patients were on corticosteroid pulses, and 133 were not. 30·3% (37/122) of patients died in the corticosteroid pulses group and 42·9% (57/133) in the non-exposed cohort. These differences (12·6% CI95% [8·54-16·65]) were statically significant (log-rank 4·72, p=0·03). We performed PSM using the exact method. Mortality differences remained in the PSM group (log-rank 5·31, p=0·021) and were still significant after a Cox regression model (HR for corticosteroid pulses 0·561, p= 0·039). There were no significant differences in intensive care admission rate (p=0·173). The hospital stay was longer in the corticosteroid group (p<0,001). Interpretation: This study provides evidence about treatment with corticosteroid pulses in severe COVID-19 that might significantly reduce mortality. Strict inclusion and exclusion criteria with that selection process set a reliable frame to compare mortality in both exposed and non-exposed groups. Funding: There was no funding provided.
HLA allele-specific expression loss in tumors can shorten survival and hinder immunotherapy
Authors: Filip Ioan , Orenbuch Rose , Zhao Junfei , Manji Gulam , de Maturana Evangelina López , Malats Núria , Olive Kenneth P. , Rabadan Raul 
Published: October 2020

AbstractEfficient presentation of aberrant peptide fragments by the human leukocyte antigen class I (HLA-I) genes is necessary for immune detection and killing of cancer cells. Patient HLA-I genotypes are known to impact the efficacy of cancer immunotherapy, and the somatic loss of HLA-I heterozygosity has been established as a factor in immune evasion. While global deregulated expression of HLA-I has been reported in different tumor types, the role of HLA-I allele-specific expression loss – that is, the preferential RNA expression loss of specific HLA-I alleles – has not been fully characterized in cancer. In the present study, we quantified HLA-I allele-specific expression (ASE) across eleven TCGA tumor types using a novel method from input RNA and whole-exome sequencing data. Allele-specific loss in at least one of the three HLA-I genes (ASE loss) was pervasive and associated to worse overall survival across tumor types, including pancreatic adenocarcinomas, prostate carcinomas and glioblastomas, among others. In particular, our analysis shows that detection of neoantigens with binding affinity to the specific HLA-I genes subject to ASE loss was a top prognostic indicator of overall survival. Additionally, we found that ASE loss hindered immunotherapy in retrospective analyses. Together, these results highlight the prevalence of HLA-I ASE loss – a previously uncharacterized phenomenon in cancer – and provide initial evidence of its clinical significance in cancer prognosis and immunotherapy treatment.
Long Covid: quantitative and qualitative analyses of online Long Haulers’ experiences, emotions and practices in the UK
Authors: Martin Sam , Miyake Esperanza 
Published: October 2020

WITHDRAWAL/DISCLAIMER STATEMENTThe authors have withdrawn this manuscript because of issues that have been raised regarding the process of data collection. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
COVID-19 Classification of X-ray Images Using Deep Neural Networks
Authors: Goldstein Elisha , Keidar Daphna , Yaron Daniel , Shachar Yair , Blass Ayelet , Charbinsky Leonid , Aharony Israel , Lifshitz Liza , Lumelsky Dimitri , Neeman Ziv , Mizrachi Matti , Hajouj Majd , Eizenbach Nethanel , Sela Eyal , Weiss Chedva , Levin Philip , Benjaminov Ofer , Bachar Gil N , Tamir Shlomit , Rapson Yael , Suhami Dror , dror amiel a , Bogot Naama , Grubstein Ahuva , Shabsin Nogah , Elyada Yishai M , Eldar Yonina 
Published: October 2020

AbstractObjectivesIn the midst of the coronavirus disease 2019 (COVID-19) outbreak, chest X-ray (CXR) imaging is playing an important role in diagnosis and monitoring of patients with COVID-19. Machine learning solutions have been shown to be useful for X-ray analysis and classification in a range of medical contexts. In this study, we propose a machine learning model for detection of patients tested positive for COVID-19 from CXRs that were collected from inpatients hospitalized in four different hospitals. We additionally present a tool for retrieving similar patients according to the model’s results on their CXRs.MethodsIn this retrospective study, 1384 frontal CXRs, of COVID-19 confirmed patients imaged between March-August 2020, and 1024 matching CXRs of non-COVID patients imaged before the pandemic, were collected and used to build a deep learning classifier for detecting patients positive for COVID-19. The classifier consists of an ensemble of pre-trained deep neural networks (DNNS), specifically, ReNet34, ReNet50, ReNet152, vgg16, and is enhanced by data augmentation and lung segmentation. We further implemented a nearest-neighbors algorithm that uses DNN-based image embeddings to retrieve the images most similar to a given image.ResultsOur model achieved accuracy of 90.3%, (95%CI: 86.3%-93.7%) specificity of 90% (95%CI: 84.3%-94%), and sensitivity of 90.5% (95%CI: 85%-94%) on a test dataset comprising 15% (350/2326) of the original images. The AUC of the ROC curve is 0.96 (95%CI: 0.93-0.97).ConclusionWe provide deep learning models, trained and evaluated on CXRs that can assist medical efforts and reduce medical staff workload in handling COVID-19.Key PointsA machine learning model was able to detect chest X-ray (CXR) images of patients tested positive for COVID-19 with accuracy and detection rate above 90%.A tool was created for finding existing CXR images with imaging characteristics most similar to a given CXR, according to the model’s image embeddings.
Network controllability in transmodal cortex predicts psychosis spectrum symptoms
Authors: Parkes Linden , Moore Tyler M. , Calkins Monica E. , Cieslak Matthew , Roalf David R. , Wolf Daniel H. , Gur Ruben C. , Gur Raquel E. , Satterthwaite Theodore D. , Bassett Danielle S. 
Published: October 2020

ABSTRACTBackgroundThe psychosis spectrum is associated with structural dysconnectivity concentrated in transmodal association cortex. However, understanding of this pathophysiology has been limited by an exclusive focus on the direct connections to a region. Using Network Control Theory, we measured variation in both direct and indirect structural connections to a region to gain new insights into the pathophysiology of the psychosis spectrum.MethodsWe used psychosis symptom data and structural connectivity in 1,068 youths aged 8 to 22 years from the Philadelphia Neurodevelopmental Cohort. Applying a Network Control Theory metric called average controllability, we estimated each brain region’s capacity to leverage its direct and indirect structural connections to control linear brain dynamics. Next, using non-linear regression, we determined the accuracy with which average controllability could predict negative and positive psychosis spectrum symptoms in out-of-sample testing. We also compared prediction performance for average controllability versus strength, which indexes only direct connections to a region. Finally, we assessed how the prediction performance for psychosis spectrum symptoms varied over the functional hierarchy spanning unimodal to transmodal cortex.ResultsAverage controllability outperformed strength at predicting positive psychosis spectrum symptoms, demonstrating that indexing indirect structural connections to a region improved prediction performance. Critically, improved prediction was concentrated in association cortex for average controllability, whereas prediction performance for strength was uniform across the cortex, suggesting that indexing indirect connections is crucial in association cortex.ConclusionsExamining inter-individual variation in direct and indirect structural connections to association cortex is crucial for accurate prediction of positive psychosis spectrum symptoms.
Use of seat belts among public transport drivers in Tacna, Peru: Prevalence and risk factors
Authors: Miñan-Tapia Armando , Torres-Riveros Gloria S. , Choque-Vargas José , Aycachi-Incacoña Madeleyni , Flores-Valdez Neil , Vargas-Anahua Orlando , Mejia Christian R. 
Published: October 2020

AbstractIntroductionThere are individuals who still refuse to wear seat belts, despite its effectiveness in reducing morbidity and mortality in road traffic accidents. We aimed to determine the prevalence and risk factors according to the use of seat belts among public transport drivers in Tacna, Peru.MethodologyThis analytical transversal study was carried out among public transport drivers (buses and taxis) in a Peruvian city. Questionnaires were used to evaluate the general and occupational characteristics and the use of seat belts (observed). Descriptive statistics and risk factors were obtained, these latter through generalized linear models.ResultsOf the 460 drivers, 77% used their seat belts, with a difference in use depending on the type of public transport (p<0.001). In the multivariate model, the risk of not using the belt was associated with the following: older age (p<0.001), having complete studies (p<0.001), a higher level/category of driving license (3 categories had p<0.001), having a higher number of previous road traffic accidents (p=0.011), and received medical attention in that accident (p<0.001), those who reported using a cell phone while driving (p=0.005), if the co-driver’s belt had 3 anchorage points (p<0.001), and working for > 5 hours that day (p=0.002). However, male drivers and those who had their belt with 3 anchorage points had greater use (both p<0.001).ConclusionsOne in five drivers did not use a seat belt, and important characteristics of those who did not comply with this traffic law were evaluated to generate control and intervention measures.
Real-time clinician text feeds from electronic health records
Authors: Teo James , Dinu Vlad , Bernal William , Davidson Phil , Oliynyk Vitaliy , Breen Cormac , Barker Richard D , Dobson Richard 
Published: October 2020

AbstractAnalyses of search engine and social media feeds have been attempted for infectious disease outbreaks1, but have been found to be susceptible to artefactual distortions from health scares or keyword spamming in social media or the public internet 2–4. We describe an approach using real-time aggregation of keywords and phrases of free text from real-time clinician-generated documentation in electronic health records to produce a customisable real-time viral pneumonia signal providing up to 2 days warning for secondary care capacity planning. This low-cost approach is open-source, is locally customisable, is not dependent on any specific electronic health record system and can be deployed at multiple organisational scales.
Neurogenetic and genomic approaches reveal roles for Dpr/DIP cell adhesion molecules inDrosophilareproductive behavior
Authors: Brovero Savannah G , Fortier Julia C , Hu Hongru , Lovejoy Pamela C , Newell Nicole R , Palmateer Colleen M , Tzeng Ruei-Ying , Lee Pei-Tseng , Zinn Kai , Arbeitman Michelle N 
Published: October 2020

AbstractDrosophilareproductive behaviors are directed byfruitlessneurons (fru P1isoforms). A reanalysis of genomic studies shows that genes encodingdprandDIPImmunoglobulin superfamily (IgSF) members are expressed infru P1neurons. Eachfru P1anddpr/DIP(fru P1∩dpr/DIP) overlapping expression pattern is similar in both sexes, with dimorphism in neuronal morphology and cell number. Behavioral studies offru P1∩dpr/DIPperturbation genotypes point to the mushroom body functioning together with the lateral protocerebral complex. Functionally, we find that perturbations of sex hierarchy genes andDIP-εchanges sex-specific morphology offru P1∩DIP-αneurons. A single-cell RNA-seq analysis shows that theDIPshave high expression in a restricted set offru P1neurons, whereas thedprsare expressed in larger set of neurons at intermediate levels, with a myriad of combinations.
Vascular origins of low-frequency oscillations in the cerebrospinal fluid signal in resting-state fMRI: Interpretation using photoplethysmography
Authors: Attarpour Ahmadreza , Ward James , Chen J. Jean 
Published: October 2020

AbstractSlow and rhythmic spontaneous oscillations of cerebral blood flow are well known to have diagnostic utility, notably frequencies of 0.008-0.03 Hz (B-waves) and 0.05-0.15Hz (Mayer waves or M waves). However, intracranial measurements of these oscillations have been difficult. Oscillations in the cerebrospinal fluid (CSF), which are influenced by the cardiac pulse wave, represent a possible avenue for non-invasively tracking these oscillations using resting-state functional MRI (rs-fMRI), and have been used to correct for vascular oscillations in rs-fMRI functional connectivity calculations. However, the relationship between low-frequency CSF and vascular oscillations is unclear. In this study, we investigate this relationship using fast simultaneous multi-slice rs-fMRI coupled with fingertip photoplethysmography (PPG). We not only extract B-wave and M-wave range spectral power from the PPG signal, but also derive the pulse-intensity ratio (PIR, a surrogate of slow blood-pressure oscillations), the second-derivative of the PPG (SDPPG, a surrogate of arterial stiffness) and heart-rate variability (HRV). The main findings of this study are: (1) signals in different CSF regions (ROIs) are not equivalent in their vascular contributions or in their associations with vascular and tissue rs-fMRI signals; (2) the PPG signal contains the highest signal contribution from the M-wave range, while PIR contains the highest signal contribution from the B-wave range; (3) in the low-frequency range, PIR is more strongly associated with rs-fMRI signal in the CSF than PPG itself, and than HRV and SDPPG; (4) PPG-related vascular oscillations only contribute to < 20% of the CSF signal in rs-fMRI, insufficient support for the assumption that low-frequency CSF signal fluctuations directly reflect vascular oscillations. These findings caution the use of CSF as a monolithic region for extracting physiological nuisance regressors in rs-fMRI applications. They also pave the way for using rs-fMRI in the CSF as a potential tool for tracking cerebrovascular health through, for instance the strong relationship between PIR and the CSF signal.
Adhesion to type I collagen fibrous gels induces E- to N-cadherin switching without other EMT-related phenotypes in lung carcinoma cell A549
Authors: Fujisaki Hitomi , Futaki Sugiko , Yamada Masashi , Sekiguchi Kiyotoshi , Hayashi Toshihiko , Hattori Shunji 
Published: October 2020

AbstractIn culture system, environmental factors, such as increasing exogenous growth factors and adhesion to type I collagen (Col-I) induce epithelial-to-mesenchymal transition (EMT) in cells. Col-I molecules maintain a non-fibril form under acidic conditions, and they reassemble into fibrils under physiological conditions. Col-I fibrils often assemble to form three-dimensional gels. The gels and non-gel-form of Col-I can be utilized as culture substrates and different gel-forming state often elicit different cell behaviors. However, gel-form dependent effects on cell behaviors, including EMT induction, remain unclear. EMT induction in lung cancer cell line A549 has been reported via adhesion to Col-I but the effects of gel form dependency are unelucidated. This study investigated the changes in EMT-related behaviors in A549 cells cultured on Col-I gels.We examined cell morphology, proliferation, single-cell migration and expression of EMT-related features in A549 cells cultured on gels or non-gel form of Col-I and non-treated dish with or without transforming growth factor (TGF)-β1. On Col-I gels, some cells kept cell–cell contacts and formed clusters, others maintained single-cell form. In cell–cell contact regions, E-cadherin expression was downregulated, whereas that of N-cadherin was upregulated. Vimentin and integrins α2 and β1 expression were not increased. In TGF-β1-treated A549 cells, cadherin switched from E- to N-cadherin. Their morphology changed to a mesenchymal form and cells scattered with no cluster formation. Vimentin, integrins α2 and β1 expression were upregulated. Thus, we concluded that culture on Col-I fibrous gels induced E- to N-cadherin switching without other EMT-related phenotypes in A549 cells.
Diversity and asynchrony in soil microbial communities stabilizes ecosystem functioning
Authors: Wagg Cameron , Hautier Yann , Pellkofer Sarah , Banerjee Samiran , Schmid Bernhard , van der Heijden Marcel G.A. 
Published: October 2020

AbstractTheoretical and empirical advances have revealed the importance of biodiversity for stabilizing ecosystem functions through time. Yet despite the global degradation of soils, how the loss of soil microbial diversity can de-stabilizes ecosystem functioning is unknown. Here we experimentally quantified the contribution diversity and the temporal dynamics in the composition of soil microbial communities to the temporal stability of four key ecosystem functions related to nutrient and carbon cycling. Soil microbial diversity loss reduced the temporal stability of all ecosystem functions and was particularly strong when over 50% of microbial taxa were lost. The stabilizing effect of soil biodiversity was linked to asynchrony among microbial taxa whereby different soil fungi and bacteria were associated with different ecosystem functions at different times. Our results emphasize the need to conserve soil biodiversity in order to ensure the reliable provisioning of multiple ecosystems functions that soils provide to society.
Malignant astrocyte swelling and impaired glutamate clearance drive the expansion of injurious spreading depolarization foci
Authors: Menyhárt Ákos , Frank Rita , Farkas Attila E. , Süle Zoltán , Varga Viktória É. , Nyúl-Tóth Ádám , Meiller Anne , Ivánkovits-Kiss Orsolya , Lemale Coline L. , Szabó Írisz , Tóth Réka , Zölei-Szénási Dániel , Woitzik Johannes , Marinesco Stephane , Krizbai István A. , Bari Ferenc , Dreier Jens P. , Farkas Eszter 
Published: October 2020

AbstractSpreading depolarizations (SD) indicate infarct maturation and predict worse clinical outcome in ischemic stroke. We demonstrate here in rodents that brain edema formation upon ischemic stroke impairs astroglial glutamate clearance and increases the tissue area invaded by SD. The cytotoxic glutamate accumulation predisposes an extensive bulk of tissue for a yet undescribed simultaneous depolarization (SiD). We confirm in rat brain slices under hypo-osmotic stress that SiD is the pathological expansion of prior SD foci, is associated with astrocyte swelling and triggers oncotic neuron death. The blockade of astrocytic aquaporin-4 channels and Na+/K+/Cl-co-transporters, or volume-regulated anion channels mitigated slice edema, glutamate accumulation and SiD occurrence. Reversal of slice edema by hyperosmotic treatment counteracted glutamate accumulation and prevented SiD. In contrast, paralysis of astrocyte metabolism or inhibition of astrocyte glutamate uptake reproduced the SiD phenotype. We discuss our results in the light of evidence for SiD in the human cortex. Our results emphasize the need of preventive osmotherapy in ischemic stroke.