bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain strain rate response: addressing computational ambiguity and experimental data for model validation
Authors: Zhou Zhou , Li Xiaogai , Liu Yuzhe , Hardy Warren N. , Kleiven Svein 
Published: February 2022

AbstractTraumatic brain injury (TBI) is an alarming global public health issue with high morbidity and mortality rates. Although the causal link between external insults and consequent brain injury remains largely elusive, both strain and strain rate are generally recognized as crucial factors for TBI onsets. With respect to the flourishment of strain-based investigation, ambiguity and inconsistency are noted in the scheme for strain rate calculation within the TBI research community. Furthermore, there is no experimental data that can be used to validate the strain rate responses of finite element (FE) models of the human brain. Thus, the current work presented a theoretical clarification of two commonly used strain rate computational schemes: the strain rate was either calculated as the time derivative of strain or derived from the rate of deformation tensor. To further substantiate the theoretical disparity, these two schemes were respectively implemented to estimate the strain rate responses from a previous-published cadaveric experiment and an FE head model secondary to a concussive impact. The results clearly showed scheme-dependent responses, both in the experimentally determined principal strain rate and FE model-derived principal and tract-oriented strain rates. The results highlight that cross-scheme comparison of strain rate responses is inappropriate, and the utilized strain rate computational scheme needs to be reported in future studies. The newly calculated experimental strain rate curves in the supplementary material can be used for strain rate validation of FE head models.
Olfactory detection and discrimination in domestic dogs (Canis lupus familiaris)
Authors: Ferrando Elodie , Dahl Christoph D. 
Published: February 2022

AbstractThe extraordinary olfactory capabilities in detection and rescue dogs are well-known. However, the olfactory performance varies by breed and search environment (Jezierski et al., 2014), as well as by the quantity of training (Horowitz et al., 2013). While detection of an olfactory cue inherently demands a judgment regarding the presence or absence of a cue at a given location, olfactory discrimination requires an assessment of quantity, a task demanding more attention and, hence, decreasing reliability as an informational source (Horowitz et al., 2013). This study aims at gaining more clarity on detection and discrimination of olfactory cues in untrained dogs and in a variety of dog breeds. Using a two-alternative forced choice (2AFC) paradigm, we assessed olfactory detection scores by presenting a varied quantity of food reward under one or the other hidden cup, and discrimination scores by presenting two varied quantities of food reward under both hidden cups. We found relatively reliable detection performances across all breeds and limited discrimination abilities, modulated by breed. We discuss our findings in relation to the cognitive demands imposed by the tasks and the cephalic index of the dog breeds.
Cell Type Composition Analysis: Comparison of statistical methods
Authors: Simmons Sean 
Published: February 2022

AbstractMeasuring changes in cell type composition between conditions (disease vs not, knockout vs wild type, treated vs not, etc) is fast becoming a standard step in single cell RNA-Seq analysis. Despite that, there is no agreement on the best approach for this type of analysis. As such, we decided to test numerous methods for cell type composition analysis, seeing how they performed in terms of false positive rate and power. Though there is not one clear winner, we do find two method (the propeller method with asin normalization and Dirichlet regression with the alternative parameterization) perform well in most situations. Most importantly, consistent with results in differential expression analysis, we see that it is important to take into account sample to sample (mouse to mouse, person to person, etc) variability to avoid high false positive rates. We also see evidence that aggregation (aka pseudobulk) based method slightly outperform the mixed model methods we tested.
Theta band-power shapes amyloid-driven longitudinal EEG changes in pre-clinical Alzheimer’s Disease
Authors: Spinelli Giuseppe , Bakardjian Hovagim , Schwartz Denis , Potier Marie-Claude , Habert Marie-Odile , Levy M. , Dubois Bruno , George Nathalie 
Published: February 2022

AbstractAlzheimer’s Disease (AD) includes progressive symptoms spread along a continuum of pre-clinical (pre-AD) and clinical stages. Pre-AD refers to cognitively healthy individuals with presence of positive pathophysiological biomarkers of AD (i.e., markers of amyloidopathy and tauopathy). Although numerous studies uncovered the neuro-cognitive changes of AD, very little is known on the natural history of brain lesions and modifications of brain networks of pre-AD. To address this issue, we analysed resting-state EEG data of 318 cognitively healthy individuals with subjective memory complains from the INSIGHT-preAD cohort at the time of their first visit (M0) and two-years later (M24). Using 18F-florbetapir PET-scanner, subjects were stratified between amyloid positive (A-; n=230) and amyloid negative (A+; n=88) groups. Differences between A+ and A- individuals were estimated at source level in each band of the EEG power spectrum. At M0, we found an increase of theta-band power in the mid-frontal cortex in A+ compared to A-. No significant association was found between mid-frontal theta power and the individuals’ cognitive performance. While the very same effect was not replicated at M24, theta-band power increased in A+ relative to A- individuals in the posterior cingulate cortex and the pre-cuneus. Furthermore, alpha band revealed a peculiar decremental trend in posterior brain regions in the A+ relative to the A- group only at M24. These results provide the first source-level longitudinal evidence on the impact of brain amyloidosis on the EEG dynamics of a large-scale, monocentric cohort of pre-AD. Theta-band power increase over the mid-frontal and mid-posterior cortices suggests an hypoactivation of the default-mode network in individuals at-risk of AD and a non-linear longitudinal progression of the AD-spectrum.
Mutations of Omicron variant at the interface of the receptor domain motif and human angiotensin-converting enzyme-2
Authors: Adhikari Puja , Jawad Bahaa , Podgornik Rudolf , Ching Wai-Yim 
Published: February 2022

AbstractThe most recent Omicron variant of SARS-CoV-2 has caused global concern and anxiety. The only thing certain about this strain, with large number of mutations in the spike protein, is that it spreads quickly, seems to evade immune defense and mitigates the benefits of existing vaccines. Based on the ultra-large-scale ab initio computational modeling of the receptor binding motif (RBM) and human angiotensin-converting enzyme-2 (ACE2) interface we provide the details of the effect of Omicron mutations at the fundamental atomic scale level. In-depth analysis anchored in the novel concept of amino acid-amino acid bond pair units (AABPU), indicates that mutations in the Omicron variant are connected with (i) significant changes in the shape and structure of AABPU components, together with (ii) significant increase in the positive partial charge which facilitates the interaction with ACE2. The calculated bond order, based on AABPU, reveals that the Omicron mutations increase the binding strength of RBM to ACE2. Our findings correlate with and are instrumental to explain the current observations and can contribute to the prediction of next potential new variant of concern.
Schrödinger’s range-shifting cat: analytic predictions for the effect of asymmetric environmental performance on climate change responses
Authors: Terry J. Christopher D. , O’Sullivan Jacob D. , Rossberg A. G. 
Published: February 2022

AbstractAnalytic models for how species will respond to climate change can highlight key parameter dependencies. By mapping equations for population dynamics onto corresponding well-studied problems from quantum mechanics we derive analytical results for the frequently observed case of asymmetric environmental response curves. We derive expressions in terms of parameters representing climate velocity, dispersal rate, maximum growth rate, niche width, high-frequency climate variability and environmental performance curve skew for three key responses: 1) population persistence, 2) lag between range displacement and climate displacement, 3) location of maximum population sensitivity. Surprisingly, under our model assumptions, the direction of performance curve asymmetry does not strongly contribute to either persistence or lags. Conservation measures to support range-shifting populations may have most benefit near their environmental optimum or where the environmental dependence is shallow, irrespective of whether this is the ‘leading’ or ‘trailing’ edge. A metapopulation simulation corroborates our results.
PELP: accounting for missing data in neural time series by Periodic Estimation of Lost Packets
Authors: Dastin-van Rijn Evan M. , Provenza Nicole R. , Goodman Wayne K. , Harrison Matthew T. , Borton David. A. 
Published: February 2022

AbstractObjectiveImplanted electrical stimulators with sensing capabilities have enabled the development of closed-loop neuromodulation therapies capable of responding to patient needs in real-time. Through a combination of rechargeable technologies and wireless data transmission, it is now possible for researchers to acquire extensive neural recordings from human participants in naturalistic settings using these bidirectional devices. However, data losses during wireless transmission hamper processing and the identification of neural signals of interest, driving the need for methodologies to properly estimate the impact of data loss.ApproachTo accurately reconstruct the timing of data containing losses, we have developed a method called Periodic Estimation of Lost Packets (PELP) to precisely determine the number of samples lost from implanted recordings during active stimulation. PELP leverages a data-driven procedure for determining the period of stimulation and the knowledge that stimulation continues identically during periods where data are missing to accurately account for the number of samples lost.Main resultsUsing simulated stimulation added to collected human EEG data, we show that PELP is robust to a range of stimulation waveforms and noise characteristics. Lastly, we successfully applied PELP to local field potential (LFP) recordings from an implanted, bidirectional device using data recorded in the clinic and the patient’s own home.SignificanceBy effectively accounting for the timing of missing data, PELP enables the analysis of complex, naturalistic neural time series data from bidirectional implanted devices aiding in the development of novel therapeutic approaches. NCT04806516 (ClinicalTrials.gov).
SARS-CoV-2 infects, replicates, elevates angiotensin II and activates immune cells in human testes
Authors: Costa Guilherme M.J. , Lacerda Samyra M.S.N. , Figueiredo André F.A. , Wnuk Natália T. , Brener Marcos R. G. , Campolina-Silva Gabriel H. , Kauffmann-Zeh Andrea , Pacifico Lucila GG , Versiani Alice F. , Andrade Lídia M. , Antunes Maísa M. , Souza Fernanda R. , Cassali Geovanni D. , Caldeira-Brant André L. , Chiarini-Garcia Hélio , Costa Vivian V. , da Fonseca Flavio G. , Nogueira Maurício L. , Campos Guilherme R. F. , Kangussu Lucas M. , Martins Estefânia M. N. , Antonio Loudiana M. , Bittar Cintia , Rahal Paula , Aguiar Renato S. , Mendes Bárbara P. , Procópio Marcela S. , Furtado Thiago P. , Guimaraes Yuri L , Menezes Gustavo B , Martinez-Marchal Ana , Brieno-Enriquez Miguel , Orwig Kyle E. , Furtado Marcelo H. 
Published: February 2022

ABSTRACTAlthough much has been published since the first cases of COVID-19, there remain unanswered questions regarding SARS-CoV-2 impact on testes and the potential consequences for reproductive health. We investigated testicular alterations in deceased COVID-19-patients, the precise location of the virus, its replicative activity, and the molecules involved in the pathogenesis. We found that SARS-CoV-2 testicular tropism is higher than previously thought and that reliable viral detection in the testis requires sensitive nanosensoring or RT-qPCR using a specific methodology. Macrophages and spermatogonial cells are the main SARS-CoV-2 lodging sites and where new virions form inside the Endoplasmic Reticulum Golgi Intermediate Complex. Moreover, we showed infiltrative infected monocytes migrating into the testicular parenchyma. SARS-CoV-2 maintains its replicative and infective abilities long after the patient’s infection, suggesting that the testes may serve as a viral sanctuary. Further, infected testes show thickening of the tunica propria, germ cell apoptosis, Sertoli cell barrier loss, evident hemorrhage, angiogenesis, Leydig cell inhibition, inflammation, and fibrosis. Finally, our findings indicate that high angiotensin II levels and activation of mast cells and macrophages may be critical for testicular pathogenesis. Importantly, our data suggest that patients who become critically ill exhibit severe damages and may harbor the active virus in testes.
Single cell sequencing analysis uncovers genetics-influenced CD16+monocytes and memory CD8+T cells involved in severe COVID-19
Authors: Ma Yunlong , Qiu Fei , Deng Chunyu , Li Jingjing , Huang Yukuan , Wu Zeyi , Zhou Yijun , Zhang Yaru , Xiong Yichun , Yao Yinghao , Zhong Yigang , Qu Jia , Su Jianzhong 
Published: February 2022

AbstractBackgroundUnderstanding the host genetic architecture and viral immunity contributes to the development of effective vaccines and therapeutics for controlling the COVID-19 pandemic. Alterations of immune responses in peripheral blood mononuclear cells play a crucial role in the detrimental progression of COVID-19. However, the effects of host genetic factors on immune responses for severe COVID-19 remain largely unknown.MethodsWe constructed a powerful computational framework to characterize the host genetics-influenced immune cell subpopulations for severe COVID-19 by integrating GWAS summary statistics (N = 969,689 samples) with four independent scRNA-seq datasets (N = 606,534 cells).ResultsWe found that 34 risk genes were significantly associated with severe COVID-19, and the number of highly-expressed genetics-risk genes increased with the severity of COVID-19. Three cell-subtypes that are CD16+monocytes, megakaryocytes, and memory CD8+T cells were significantly enriched by COVID-19-related genetic association signals. Notably, three causal risk genes of CCR1, CXCR6, and ABO were specifically expressed in these three cell types, respectively. CCR1+CD16+monocytes and ABO+ megakaryocytes with significant up-regulated genes including S100A12, S100A8, S100A9, and IFITM1 confer higher risk to the cytokine storms among severe patients. CXCR6+ memory CD8+ T cells exhibit a notable polyfunctionality of multiple immunologic features, including elevation of proliferation, migration, and chemotaxis. Moreover, we observed a prominent increase in cell-cell interactions of both CCR1+ CD16+monocytes and CXCR6+ memory CD8+T cells in severe patients compared to normal controls among both PBMCs and lung tissues, and elevated interactions with epithelial cells could contribute to enhance the resident to lung airway for against COVID-19 infection.ConclusionsWe uncover a major genetics-modulated immunological shift between mild and severe infection, including an increase in up-regulated genetic-risk genes, excessive secreted inflammatory cytokines, and functional immune cell subsets contributing high risk to severity, which provides novel insights in parsing the host genetics-influenced immune cells for severe COVID-19.
A Bibliometric Analysis of Ophthalmology Resident Research Productivity in the United States
Authors: Huang Austin , Kim Sarah , Zhu Harrison , Pathare Nihar , Ooi Xin Yee , Kirby R. Parker , Yoon Stephen P. , Al-Mohtaseb Zaina 
Published: February 2022

ABSTRACTPurposeTo quantify scholarly activity of ophthalmology residents during residency and assess what factors may be associated with greater research productivity of these residents.MethodsOphthalmology residents who graduated in 2021 were identified from their respective program websites. Bibliometric data published by these residents between the beginning of their PGY-2 year (July 1st, 2018) until three months after graduation (September 30th, 2021) were captured through searches via PubMed, Scopus, and Google Scholar. The association of the following factors with greater research productivity numbers was analyzed: residency tier, medical school rank, sex, doctorate degree, type of medical degree, and international medical graduate status. Residency programs were sorted into five tiers by Doximity “reputation” and medical schools were stratified into US News Top 40 and non-Top 40 schools.ResultsWe found 418 ophthalmology residents from 98 residency programs. These residents published a mean (±SD) number of 2.68±3.81 peer-reviewed publications, 2.39±3.40 ophthalmology-related publications, and 1.18±1.96 first-author publications each. The mean (±SD) h-index for this cohort was 0.79±1.17. Upon multivariate analysis, we discovered significant correlations between both residency tier and medical school rank and all bibliometric variables assessed. Pairwise comparisons revealed that residents from higher tier programs had greater research productivity numbers than those from lower tier programs.ConclusionsWe obtained bibliometric standards for ophthalmology residents on a national scale. Residents who graduated from higher-ranked residency programs and medical schools possessed higher h-indices and published more peer-reviewed publications, ophthalmology-related articles, and first author publications.
Improving estimates of social contact patterns for the airborne transmission of respiratory pathogens
Authors: McCreesh Nicky , Mohlamonyane Mbali , Edwards Anita , Olivier Stephen , Dikgale Keabetswe , Dayi Njabulo , Gareta Dickman , Wood Robin , Grant Alison D , White Richard G , Middelkoop Keren 
Published: February 2022

AbstractBackgroundData on social contact patterns are widely used to parameterise age-mixing matrices in mathematical models of infectious diseases designed to help understand transmission patterns or estimate intervention impacts. Despite this, little attention is given to how social contact data are collected and analysed, or how the types of contact most relevant for transmission may vary between different infections. In particular, the majority of studies focus on close contacts only – people spoken to face-to-face. This may be appropriate for infections spread primarily by droplet transmission, but it neglects the larger numbers of ‘shared air’ casual contacts who may be at risk from airborne transmission of pathogens such as Mycobacterium tuberculosis, measles, and SARS-CoV-2.MethodsWe conducted social contact surveys in communities in two provinces of South Africa in 2019 (KwaZulu-Natal and Western Cape). In line with most studies, we collected data on people spoken to (close contacts). We also collected data on places visited and people present, allowing casual contact patterns to be estimated. Using these data, we estimated age mixing patterns relevant for i) droplet and ii) non-saturating airborne transmission. We also estimated a third category of pattern relevant for the transmission of iii) Mycobacterium tuberculosis (Mtb), an airborne infection where saturation of household contacts plays an important role in transmission dynamics.ResultsEstimated contact patterns by age did not vary greatly between the three transmission routes/infections, in either setting. In both communities, relative to other adult age groups, overall contact intensities were lower in 50+ year olds when considering contact relevant for non-saturating airborne transmission or the transmission of Mycobacterium tuberculosis than when considering contact relevant for droplet transmission.ConclusionsOur findings provide some reassurance that the widespread use of close contact data to parameterise age-mixing matrices for transmission models of airborne infections may not be resulting in major inaccuracies. The contribution of older age groups to transmission may be over-estimated, however. There is a need for future social contact surveys to collect data on casual contacts, to investigate whether our findings can be generalised to a wider range of settings, and to improve model predictions for infections with substantial airborne transmission.
First genotype-phenotype study in TBX4 syndrome: gain-of-function mutations causative for lung disease
Authors: Prapa Matina , Lago-Docampo Mauro , Swietlik Emilia M. , Montani David , Eyries Mélanie , Humbert Marc , Welch Carrie C.L. , Chung Wendy , Berger Rolf M.F. , Bogaard Ham Jan , Danhaive Olivier , Escribano-Subías Pilar , Gall Henning , Girerd Barbara , Hernandez-Gonzalez Ignacio , Holden Simon , Hunt David , Jansen Samara M.A. , Kerstjens-Frederikse Wilhelmina , Kiely David , Lapunzina Pablo , McDermott John , Moledina Shahin , Pepke-Zaba Joanna , Polwarth Gary J. , Schotte Gwen , Tenorio-Castaño Jair , Thompson A.A. Roger , Warton John , Wort Stephen J. ,   NIHR BioResource for Translational Research – Rare Diseases,   National Cohort Study of Idiopathic and Heritable PAH,   PAH Biobank Enrolling Centers’ Investigators, Megy Karyn , Mapeta Rutendo , Treacy Carmen M. , Martin Jennifer M , Li Wei , Swift Andrew J. , Upton Paul D. , Morrell Nicholas W. , Gräf Stefan , Valverde Diana 
Published: February 2022

AbstractRationaleDespite the increasing frequency ofTBX4-associated pulmonary arterial hypertension (PAH), genotype-phenotype associations are lacking and may provide important insights.MethodsWe assembled a multi-center cohort of 137 patients harboring monoallelicTBX4variants and assessed the pathogenicity of missense variation (n = 42) using a novel luciferase reporter assay containing T-BOX binding motifs. We sought genotype-phenotype correlations and undertook a comparative analysis with PAH patients withBMPR2causal variants (n = 162) or no identified variants in PAH-associated genes (n = 741) genotyped via the NIHR BioResource - Rare Diseases (NBR).ResultsFunctional assessment ofTBX4missense variants led to the novel finding of gain-of-function effects associated with older age at diagnosis of lung disease compared to loss-of-function (p = 0.038). Variants located in the T-BOX and nuclear localization domains were associated with earlier presentation (p = 0.005) and increased incidence of interstitial lung disease (p = 0.003). Event-free survival (death or transplantation) was shorter in the T-BOX group (p = 0.022) although age had a significant effect in the hazard model (p = 0.0461). Carriers ofTBX4variants were diagnosed at a younger age (p < 0.001) and had worse baseline lung function (FEV1, FVC) (p = 0.009) compared to theBMPR2and no identified causal variant groups.ConclusionsWe demonstrated that TBX4 syndrome is not strictly the result of haploinsufficiency but can also be caused by gain-of-function. The pleiotropic effects of TBX4 in lung disease may be in part explained by the differential effect of pathogenic mutations located in critical protein domains.