bluuebunny/crossref_metadata_2025_split huggingface dataset:
The XyloPhone: democratizing access to high-quality macroscopic imaging for wood and other substrates
Authors: Wiedenhoeft Alex C. 
Published: August 2020

AbstractOne rate-limiting factor in the fight against illegal logging is the lack of powerful, affordable, scalable wood identification tools for field screening. Computer vision wood identification using smartphones fitted with customized imaging peripherals offer a potential solution but to date, such peripherals suffer from one or more weaknesses: low image quality, lack of lighting control, uncontrolled magnification, unknown distortion and spherical aberration, and/or no access to or publication of the system design. To address cost, optical concerns, and open access to designs and parameters, I present the XyloPhone, a 3D printed research quality macroscopic imaging attachment adaptable to any smartphone. It provides a fixed focal distance, exclusion of ambient light, selection of visible light or UV illumination, uses the lens from a commercially available loupe, is powered by a rechargeable external battery, is fully open-sourced, and at a price point of less than 110 USD is a highly affordable tool for the laboratory or the field, and can serve as the foundational hardware for a scalable field deployable computer vision wood identification system.
REGN-COV2 antibody cocktail prevents and treats SARS-CoV-2 infection in rhesus macaques and hamsters
Authors: Baum Alina , Copin Richard , Ajithdoss Dharani , Zhou Anbo , Lanza Kathryn , Negron Nicole , Ni Min , Wei Yi , Atwal Gurinder S. , Oyejide Adelekan , Goez-Gazi Yenny , Dutton John , Clemmons Elizabeth , Staples Hilary M. , Bartley Carmen , Klaffke Benjamin , Alfson Kendra , Gazi Michal , Gonzales Olga , Dick Edward , Carrion Ricardo , Pessaint Laurent , Porto Maciel , Cook Anthony , Brown Renita , Ali Vaneesha , Greenhouse Jack , Taylor Tammy , Andersen Hanne , Lewis Mark G. , Stahl Neil , Murphy Andrew J. , Yancopoulos George D. , Kyratsous Christos A. 
Published: August 2020

AbstractAn urgent global quest for effective therapies to prevent and treat COVID-19 disease is ongoing. We previously described REGN-COV2, a cocktail of two potent neutralizing antibodies (REGN10987+REGN10933) targeting non-overlapping epitopes on the SARS-CoV-2 spike protein. In this report, we evaluate the in vivo efficacy of this antibody cocktail in both rhesus macaques and golden hamsters and demonstrate that REGN-COV-2 can greatly reduce virus load in lower and upper airway and decrease virus induced pathological sequalae when administered prophylactically or therapeutically. Our results provide evidence of the therapeutic potential of this antibody cocktail.
“A novel Organ-Chip system emulates three-dimensional architecture of the human epithelia and allows fine control of mechanical forces acting on it.”
Authors: Varone Antonio , Nguyen Justin Ke , Leng Lian , Barrile Riccardo , Sliz Josiah , Lucchesi Carolina , Wen Norman , Gravanis Achille , Hamilton Geraldine A. , Karalis Katia C. , Hinojosa Christopher D. 
Published: August 2020

ABSTRACTSuccessful translation ofin vivoexperimental data to human patients is an unmet need and a bottleneck in the development of effective therapeutics. micro technology aims to address this need with significant advancements reported recently that enable modeling of organ level function. These microengineered chips enable researcher to recreate critical elements such asin vivorelevant tissue-tissue interface, air-liquid interface, and mechanical forces, such as mechanical stretch and fluidic shear stress, are crucial in emulating tissue level functions. Here, we present the development of a new, comprehensive 3D cell-culture system, where we combined our proprietary Organ-Chip technology with recent advantages in three-dimensional organotypic culture. Leveraging microfabrication techniques, we engineered a flexible chip that consists of a channel containing an organotypic epithelium surrounded by two vacuum channels that can be actuated to stretch the hydrogel throughout its thickness. Furthermore, the ceiling of this channel is a removable lid with a built-in microchannel that can be perfused with liquid or air and removed as needed for direct access to the tissue. The floor of this channel is a porous flexible membrane in contact with a microfluidic channel that provides diffusive mass transport to and from the channel. This additional microfluidic channel can be coated with endothelial cells to emulate a blood vessel and capture endothelial interactions. Our results show that the Open-Top Chip design successfully addresses common challenges associated with the Organs-on-Chips technology, including the capability to incorporate a tissue-specific extracellular matrix gel seeded with primary stromal cells, to reproduce the architectural complexity of tissues by micropatterning the gel, that can be extracted for H&E staining. We provide proof-of-concept data on the feasibility of the system using skin and alveolar epithelial primary cells and by simulating alveolar inflammation.
Mechanism of duplex unwinding by coronavirus nsp13 helicases
Authors: Hu Xiao , Hao Wei , Qin Bo , Tian Zhiqi , Li Ziheng , Hou Pengjiao , Zhao Rong , Cui Sheng , Diao Jiajie 
Published: August 2020

AbstractThe current COVID-19 pandemic urges in-depth investigation into proteins encoded with coronavirus (CoV), especially conserved CoV replicases. The nsp13 of highly pathogenic MERS-CoV, SARS-CoV-2, and SARS-CoV exhibit the most conserved CoV replicases. Using single-molecule FRET, we observed that MERS-CoV nsp13 unwound DNA in discrete steps of approximately 9 bp when ATP was used. If another NTP was used, then the steps were only 4 to 5 bp. In dwell time analysis, we detected 3 or 4 hidden steps in each unwinding process, which indicated the hydrolysis of 3 or 4 dTTP. Based on crystallographic and biochemical studies of CoV nsp13 helicases, we modeled an unwinding mechanism similar to the spring-loaded mechanism of HCV NS3 helicase, although our model proposes that flexible 1B and stalk domains, by allowing a lag greater than 4 bp during unwinding, cause the accumulated tension on the nsp13-DNA complex. The hinge region between two RecA-like domains in SARS-CoV-2 nsp13 is intrinsically more flexible than in MERS-CoV nsp13 due to the difference of a single amino acid, which causes the former to induce significantly greater NTP hydrolysis. Our findings thus establish a blueprint for determining the unwinding mechanism of a unique helicase family.When dTTP was used as the energy source, 4 hidden steps in each individual unwinding step after 3 - 4 NTP hydrolysis were observed.An unwinding model of MERS-CoV-nsp13 which is similar to the spring-loaded mechanism of HCV NS3 helicase, except the accumulation of tension on nsp13/DNA complex is caused by the flexible 1B and stalk domains that allow a lag of 4-bp in unwinding.Comparing to MERS-CoV nsp13, the hinge region between two RecA-like domains in SARS-CoV-2 nsp13 is intrinsically more flexible due to a single amino acid difference, which contributes to the significantly higher NTP hydrolysis by SARS-CoV-2 nsp13.
Ancestry Influences on the Molecular Presentation of Tumours
Authors: Li Constance H. , Haider Syed , Boutros Paul C. 
Published: August 2020

AbstractEpidemiological studies have identified innumerable ways in which cancer presentation and behaviour is associated with patient ancestry. The molecular bases for these relationships remain largely unknown. We analyzed ancestry associations in the somatic mutational landscape of 12,774 tumours across 33 tumour-types, including 2,562 with whole-genome sequencing. Ancestry influences both the number of mutations in a tumour and the evolutionary timing of when they occur. Specific mutational signatures are associated with ancestry, reflecting potential differences in exogenous and endogenous oncogenic processes. A subset of known cancer driver genes was mutated in ancestry-associated patterns, with transcriptomic consequences. Cancer genome sequencing data is not well-balanced in epidemiologic factors; these data suggest ancestry strongly shapes the somatic mutational landscape of cancer, with potential functional implications.
Assessment of a Laboratory-Based SARS-CoV-2 Antibody Test Among Hemodialysis Patients: A Quality Improvement Initiative
Authors: Cohen Dena E. , Marlowe Gilbert , Contreras Gabriel , Sosa Marie Ann , Mendoza Jair Munoz , Lenz Oliver , Mithani Zain , Teixeiro Pura Margarita , Queija Nery , Moneda Araceli , Jeanty Jean S. , Swanzy Katie , Palecek Misha , Krishnan Mahesh , Giullian Jeffrey , Brunelli Steven M. 
Published: August 2020

AbstractIntroductionThe coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although tests to detect anti-SARS-CoV-2 antibodies have been developed, their sensitivity and specificity in hemodialysis patients have not been previously assessed.MethodsAs part of a quality improvement (QI) initiative, nasopharyngeal swabs and predialysis blood samples were collected on the same day from adult patients receiving routine hemodialysis care at clinics managed by a large dialysis organization in the greater Miami, Florida region (23 – 30 Apr 2020). Polymerase chain reaction (PCR) tests for SARS-CoV-2 and chemiluminescence immunoassays for anti-SARS-CoV2 antibodies were performed according to manufacturer-specified protocols.ResultsOf 715 participants in the QI initiative, 38 had symptomatology consistent with COVID-19 prior to or during the initiative. Among these, COVID-19 was PCR-confirmed in 14 and ruled out in 20, with the remaining 4 being inconclusive. Among the 34 patients with known COVID-19 status, the sensitivity and specificity of the antibody test were 57.1% and 85.0% when either antibody was considered. The remaining 677 patients had no record of symptoms consistent with COVID-19, nor any known exposure. Of these, 38 patients (5.6%) tested positive for anti-SARS-CoV-2 antibodies.ConclusionsThe operational characteristics of the laboratory-based antibody test make it sufficient to rule in, but not rule out, SARS-CoV-2 infection in the appropriate clinical circumstance. A substantial proportion of dialysis patients may have had asymptomatic SARS-CoV-2 infection.
Simply saliva: stability of SARS-CoV-2 detection negates the need for expensive collection devices
Authors: Ott Isabel M. , Strine Madison S. , Watkins Anne E. , Boot Maikel , Kalinich Chaney C. , Harden Christina A. , Vogels Chantal B.F. , Casanovas-Massana Arnau , Moore Adam J. , Muenker M. Catherine , Nakahata Maura , Tokuyama Maria , Nelson Allison , Fournier John , Bermejo Santos , Campbell Melissa , Datta Rupak ,   the Yale IMPACT Research team, Cruz Charles S. Dela , Farhadian Shelli F. , Ko Albert I. , Iwasaki Akiko , Grubaugh Nathan D. , Wilen Craig B. , Wyllie Anne L. 
Published: August 2020

AbstractMost currently approved strategies for the collection of saliva for COVID-19 diagnostics require specialized tubes containing buffers promoted for the stabilization of SARS-CoV-2 RNA and virus inactivation. Yet many of these are expensive, in limited supply, and not necessarily validated specifically for viral RNA. While saliva is a promising sample type as it can be reliably self-collected for the sensitive detection of SARS-CoV-2, the expense and availability of these collection tubes are prohibitive to mass testing efforts. Therefore, we investigated the stability of SARS-CoV-2 RNA and infectious virus detection from saliva without supplementation. We tested RNA stability over extended periods of time (2-25 days) and at temperatures representing at-home storage and elevated temperatures which might be experienced when cold chain transport may be unavailable. We found SARS-CoV-2 RNA in saliva from infected individuals is stable at 4°C, room temperature (∼19°C), and 30°C for prolonged periods and found limited evidence for viral replication in stored saliva samples. This work demonstrates that expensive saliva collection options involving RNA stabilization and virus inactivation buffers are not always needed, permitting the use of cheaper collection options. Affordable testing methods are urgently needed to meet current testing demands and for continued surveillance in reopening strategies.
Cost-effectiveness modelling to optimise active screening strategy for gambiense human African trypanosomiasis in the Democratic Republic of Congo
Authors: Davis Christopher N. , Rock Kat S. , Antillón Marina , Miaka Erick Mwamba , Keeling Matt J. 
Published: August 2020

AbstractGambiense human African trypanosomiasis (gHAT) has been brought under control recently with village-based active screening playing a major role in case reduction. In the eve of elimination, we investigate how to optimise active screening in villages in the Democratic Republic of Congo, such that the expenses of screening programmes can be efficiently allocated while continuing to avert morbidity and mortality. We implement a cost-effectiveness analysis using a stochastic gHAT infection model for a range of active screening strategies and we calculate the net monetary benefit (NMB) of each strategy. High-coverage active screening strategies, occurring approximately annually, attain the highest NMB. We find that, for strategies stopping after one to three years of zero case reporting, the expected cost-benefits are very similar and we highlight the current recommended strategy (three years before stopping) is likely cost-effective, in addition to providing valuable information on whether transmission has been interrupted.
The mental health and experiences of discrimination of LGBTQ+ people during the COVID-19 pandemic: Initial findings from the Queerantine Study
Authors: Kneale Dylan , Bécares Laia 
Published: August 2020

AbstractObjectiveTo assess mental health status and experiences of discrimination amongst a sample of Lesbian, Gay, Bisexual, Transgender, Queer people (LGBTQ+, the “plus” including those who don’t identify with any such label) during the COVID-19 pandemic.DesignCross-sectional web-based survey.SettingResponses were collected during the COVID-19 pandemic between April 27thand July 13th.Participants398 LGBTQ+ respondents forming an analytical sample of 310 in the main models.MethodsWe used a combined measure of gender identity or expression and sexual orientation as the main explanatory variable. We assessed mental health with the 4-item Perceived Stress Scale (PSS-4), and with the 10-item Center for Epidemiological Studies Depression scale (CES-D-10). We measured experiences of discrimination with a battery of questions that asked respondents whether they had experienced a set of discriminatory experiences because of their LGBTQ+ identity during the coronavirus pandemic. Experiences of discrimination was considered a mediating factor and examined both as an outcome as well as an explanatory variable. Models were adjusted for a range of demographic and socioeconomic variables.ResultsThe prevalence of depression and stress were both high, with the majority of the sample exhibiting significant depressive symptomology (69%). Around one-in-six respondents reported some form of discrimination since the start of the pandemic because they were LGBTQ+ (16.7%). In regression models, the average score for perceived stress increased by 1.44 (95% Confidence Interval (CI): 0.517-2.354) for those who had experienced an instance of homophobic or transphobic harassment, compared to respondents who had not. Similarly, the odds of exhibiting significant depressive symptomology (CES-D-10 scores of 10 or more) increased three-fold among those who had experienced harassment based on their gender or sexuality compared to those who had not (OR: 3.251; 95% CI: 1.168-9.052). These marked associations remained after adjustment for a number of socioeconomic and demographic covariates. Cis-female respondents who identify as gay or lesbian had the lowest scores for perceived social or depressive symptoms; conversely transgender and gender diverse individuals had the highest scores.ConclusionsWe found high levels of stress and depressive symptoms, particularly among younger and transgender and gender diverse respondents. These associations were partially explained by experiences of discrimination which had a large, consistent and pernicious impact on stress and mental health.
Automated brain morphometric biomarkers from MRI at term predict motor development in very preterm infants
Authors: Kline Julia E. , Illapani Venkata Sita Priyanka , He Lili , Parikh Nehal A. 
Published: August 2020

AbstractVery preterm infants are at high risk for motor impairments. Early intervention can improve outcomes in this cohort, but it would be most effective if clinicians could accurately identify the highest risk infants early. A number of biomarkers for motor development exist, but currently none are sufficiently accurate for early risk-stratification. We prospectively enrolled very preterm (gestational age ≤31 weeks) infants from four level-III NICUs. Structural brain MRI was performed at term-equivalent age. We used a well-established pipeline to automatically derive brain volumetrics and cortical morphometrics, cortical surface area, sulcal depth, gyrification index, and inner cortical curvature, from structural MRI. We related these objective measures to Bayley-III motor scores (overall, gross, and fine) at two-years corrected age. Lasso regression identified the three best predictive biomarkers for each motor scale from our initial feature set. In multivariable regression, we assessed the independent value of these brain biomarkers, over-and-above known predictors of motor development, to predict motor scores. 75 very preterm infants had high-quality T2-weighted MRI and completed Bayley-III motor testing. All three motor scores were positively associated with regional cortical surface area and subcortical volumes and negatively associated with cortical curvature throughout the majority of brain regions. In multivariable regression modeling, thalamic volume, curvature of the temporal lobe, and curvature of the insula were significant predictors of overall motor development on the Bayley-III, independent of known predictors. Objective brain morphometric biomarkers at term show promise in predicting motor development in very preterm infants.
The Bacterial and Viral Complexity of Postinfectious Hydrocephalus in Uganda
Authors: Paulson Joseph N. , Williams Brent L. , Hehnly Christine , Mishra Nischay , Sinnar Shamim A. , Zhang Lijun , Ssentongo Paddy , Mbabazi-Kabachelor Edith , Wijetunge Dona S. S. , von Bredow Benjamin , Mulondo Ronnie , Kiwanuka Julius , Bajunirwe Francis , Bazira Joel , Bebell Lisa M. , Burgoine Kathy , Couto-Rodriguez Mara , Ericson Jessica E. , Erickson Tim , Ferrari Matthew , Gladstone Melissa , Guo Cheng , Haran Murali , Hornig Mady , Isaacs Albert M. , Kaaya Brian Nsubuga , Kangere Sheila M. , Kulkarni Abhaya V. , Kumbakumba Elias , Li Xiaoxiao , Limbrick David D. , Magombe Joshua , Morton Sarah U. , Mugamba John , Ng James , Olupot-Olupot Peter , Onen Justin , Peterson Mallory R. , Roy Farrah , Sheldon Kathryn , Townsend Reid , Weeks Andrew D. , Whalen Andrew J. , Quackenbush John , Ssenyonga Peter , Galperin Michael Y. , Almeida Mathieu , Atkins Hannah , Warf Benjamin C. , Lipkin W. Ian , Broach James R. , Schiff Steven J. 
Published: August 2020

AbstractPostinfectious hydrocephalus (PIH), often following neonatal sepsis, is the most common cause of pediatric hydrocephalus world-wide, yet the microbial pathogens remain uncharacterized. Characterization of the microbial agents causing PIH would lead to an emphasis shift from surgical palliation of cerebrospinal fluid (CSF) accumulation to prevention. We examined blood and CSF from 100 consecutive cases of PIH and control cases of non-postinfectious hydrocephalus (NPIH) in infants in Uganda. Genomic testing was undertaken for bacterial, fungal, and parasitic DNA, DNA and RNA sequencing for viral identification, and extensive bacterial culture recovery. We uncovered a major contribution to PIH fromPaenibacillus, upon a background of frequent cytomegalovirus (CMV) infection. CMV was only found in CSF in PIH cases. A facultatively anaerobic isolate was recovered. Assembly of the genome revealed a strain ofP. thiaminolyticus. In mice, this isolate designated strainMbale, was lethal in contrast with the benign reference strain. These findings point to the value of an unbiased pan-microbial approach to characterize PIH in settings where the organisms remain unknown, and enables a pathway towards more optimal treatment and prevention of the proximate neonatal infections.One Sentence SummaryWe have discovered a novel strain of bacteria upon a frequent viral background underlying postinfectious hydrocephalus in Uganda.
Diagnostic Prediction with Sequence-of-sets Representation Learning for Clinical Events
Authors: Zhang Tianran , Chen Muhao , Bui Alex A. T. 
Published: August 2020

AbstractElectronic health records (EHRs) contain both ordered and unordered chronologies of clinical events that occur during a patient encounter. However, during data preprocessing steps, many predictive models impose a predefined order on unordered clinical events sets (e.g., alphabetical, natural order from the chart, etc.), which is potentially incompatible with the temporal nature of the sequence and predictive task. To address this issue, we propose DPSS, which seeks to capture each patient’s clinical event records as sequences of event sets. For each clinical event set, we assume that the predictive model should be invariant to the order of concurrent events and thus employ a novel permutation sampling mechanism. This paper evaluates the use of this permuted sampling method given different data-driven models for predicting a heart failure (HF) diagnosis in subsequent patient visits. Experimental results using the MIMIC-III dataset show that the permutation sampling mechanism offers improved discriminative power based on the area under the receiver operating curve (AUROC) and precision-recall curve (pr-AUC) metrics as HF diagnosis prediction becomes more robust to different data ordering schemes.
Shared loci of telomere length with brain morphology, and pleiotropy in transcriptomic and epigenomic profiles of brain
Authors: Pathak Gita A , Wendt Frank R , Levey Daniel F , Mecca Adam P , van Dyck Christopher H , Gelernter Joel , Polimanti Renato 
Published: August 2020

ABSTRACTPremature shortening of telomere length is observed in neuropsychiatric disorders. We tested genetic colocalization of seven and nine leukocyte telomere length (LTL) loci in two ancestry groups, European (EUR) and East-Asian (EAS), respectively (total n=60,601) with brain morphology measures for 101 region-of-interests (ROI) (n=21,821). The posterior probability (>90%) was observed for ‘fourth ventricle’, ‘gray matter’ and ‘cerebellar vermal lobules I-IV’ volumes. We found regulatory genes (p ≤2.47 x10−6) by integrating transcriptomic (EAS=4;EUR=5) and methylation data (EUR=17; EAS=4) of brain tissues using Summary-based Mendelian Randomization (SMR). The LTL SNP associations were tested for brain-based chromatin profiles using H-MAGMA (EUR=50; EAS=97; p ≤ 1.02 x10−6). Pathway enrichment of tissue-specific genes highlighted calcium ion transport (fetal brain) and G2/M cell cycle transition (adult brain). This study provides evidence that previously reported LTL associations with neuropsychiatric disorders could be related to a shared genetic relationship between LTL and brain structural and regulatory traits.