bluuebunny/crossref_metadata_2025_split huggingface dataset:
Concurrent anatomical, physiological and network changes in cognitively impaired multiple sclerosis patients
Authors: Jandric Danka , Lipp Ilona , Paling David , Rog David , Castellazzi Gloria , Haroon Hamied , Parkes Laura , Parker Geoff , Tomassini Valentina , Muhlert Nils 
Published: November 2020

AbstractCognitive impairment in multiple sclerosis is associated with functional connectivity abnormalities, but the pathological substrates of these abnormalities are not well understood. It has been proposed that resting-state network nodes that integrate information from disparate regions are susceptible to metabolic stress, which may impact functional connectivity. In multiple sclerosis, pathology could increase metabolic stress within axons, damaging the anatomical connections of network regions, and leading to functional connectivity changes. We tested this hypothesis by assessing whether resting state network regions that show functional connectivity abnormalities in people with cognitive impairment also show anatomical connectivity abnormalities.Multimodal MRI and neuropsychological assessments were performed in 102 relapsing remitting multiple sclerosis patients and 27 healthy controls. Patients were considered cognitively impaired if they obtained a z-score of ≤1.5 on ≥2 tests of the Brief Repeatable Battery of Neuropsychological Tests (n=55). Functional connectivity was assessed with Independent Component Analysis of resting state fMRI images, and anatomical connectivity with Anatomical Connectivity Mapping of diffusion-weighted MRI. Exploratory analyses of fractional anisotropy and cerebral blood flow changes were conducted to assess local tissue characteristics.We found significantly decreased functional connectivity in the anterior and posterior default mode networks and significant increases in the right and left frontoparietal networks in cognitively impaired relative to cognitively preserved patients. Networks showing functional abnormalities also showed reduced anatomical connectivity and white matter microstructure integrity as well as reduced local tissue cerebral blood flow.Our results identify key pathological correlates of functional connectivity abnormalities associated with impaired cognitive function in multiple sclerosis, consistent with metabolic dysfunction in functional network regions.
Comparative analysis of the first wave of the COVID-19 pandemic in South Korea, Italy, Spain, France, Germany, the United Kingdom, the USA and the New-York state
Authors: Alvarez Luis 
Published: November 2020

AbstractWe use an exponential growth model to analyze the first wave of the COVID-19 pandemic in South Korea, Italy, Spain, France, Germany, the United Kingdom, the USA and the New-York state. This model uses the number of officially reported patients tested positive and deaths to estimate an infected hindcast of the cumulative number of patients who later tested positive or who later die. For each region, an epidemic timeline is established, obtaining a precise knowledge of the chronology of the main epidemiological events during the full course of the first wave. It includes, in particular, the time that the virus has been in free circulation before the impact of the social distancing measures were observable. The results of the study suggest that among the analyzed regions, only South Korea and Germany possessed, at the beginning of the epidemic, a testing capacity that allowed to correctly follow the evolution of the epidemic. Anticipation in taking measures in these two countries caused the virus to spend less time in free circulation than in the rest of the regions. The analysis of the growth rates in the different regions suggests that the exponential growth rate of the cumulative number of infected, when the virus is in free circulation, is around 0.250737. In addition, we also study the ability of the model to properly forecast the epidemic spread at the beginning of the epidemic outbreak when very little data and information about the coronavirus were available. In the case of France, we obtain a reasonable estimate of the peak of the new cases of patients tested positive 9 days in advance and only 7 days after the implementation of a strict lockdown.
Psychosocial Health of School-aged Children during the Initial COVID-19 Safer-at-Home School mandates in Florida: A cross-sectional study
Authors: McKune Sarah , Acosta Daniel , Diaz Nick , Brittain Kaitlin , Joyce-Beaulieu Diana , Maurelli Anthony T. , Nelson Eric J. 
Published: November 2020

AbstractBackgroundGiven the emerging literature regarding the impacts of lockdown measures on mental health, this study aims to identify risk factors in school-aged children for being at risk for psychosocial disorders during the COVID-19 Safer-at-Home School mandates in FloridaMethodsA cross-sectional study was conducted in April 2020 (n=280). Bivariate analysis and logistic and multinomial logistic regression models are used to examine socio-demographic and knowledge, attitude, and practice (KAP) predictors of anxiety, depression, and obsessive- compulsive disorder (OCD).ResultsLoss of household income was associated with being at risk for depression [aOR=3.130, 95% CI= (1.41-6.97)], anxiety [aOR=2.531, 95%CI= (1.154-5.551)], and OCD [aOR=2.90, 95%CI= (1.32-6.36)]. Being female was associated with risk for depression [aOR=1.72, 95% CI=(1.02-2.93)], anxiety [aOR=1.75, 95% CI=(1.04-2.97)], and OCD[aOR=1.764, 95%CI= (1.027-3.028)]. Parental practices that are protective against COVID-19 were associated with children being at risk of depression [aOR=1.55, 95% CI= (1.04-2.31)]. Being at a lower school level was risk factor for anxiety and OCD.ConclusionsEfforts to address mental health risk in children, as a result schools should prioritize girls, younger children, and children of families who lose income. Limiting the spread of COVID-19 through school closure may exacerbate the risk of psychosocial disorders in children, thus school administrators should move quickly to target those at greatest risk.
My voice therefore I spoke: sense of agency over speech enhanced in hearing self-voice
Authors: Ohata Ryu , Asai Tomohisa , Imaizumi Shu , Imamizu Hiroshi 
Published: November 2020

AbstractThe subjective experience of causing an action is known as the sense of agency. Dysfunction in the sense of agency has been suggested as a cause of auditory hallucinations (AHs), an important diagnostic criterion for schizophrenia. However, agency over speech has not been extensively characterized in previous empirical studies. Here, we examine both implicit and explicit measures of the sense of agency and reveal bottom-up and top-down components that constitute self-agency during speech. The first is action-outcome causality, which is perceived based on a low-level sensorimotor process when hearing their own voice following their speech. The second component is self-voice identity, which is embedded in the acoustic quality of voice and dominantly influences agency over speech at the cognitive judgment level. Our findings provide profound insight into the sense of agency over speech and present an informative perspective for understanding aberrant experience in AHs.
BCG vaccine derived peptides induce SARS-CoV-2 T cell cross-reactivity
Authors: Eggenhuizen Peter J. , Ng Boaz H. , Chang Janet , Fell Ashleigh L. , Wong Wey Y. , Gan Poh- Yi , Holdsworth Stephen R. , Ooi Joshua D. 
Published: November 2020

AbstractEpidemiological studies suggest that the Bacillus Calmette-Guérin (BCG) vaccine may have protective effects against coronavirus disease 2019 (COVID-19); and, there are now more than 15 ongoing clinical trials seeking to determine if BCG vaccination can prevent or reduce the severity of COVID-19 (1). However, the mechanism by which BCG vaccination can induce a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific T cell response is unknown. Here, in silico, we identify 8 BCG derived peptides with significant sequence homology to either SARS-CoV-2 NSP3 or NSP13 derived peptides. Using an in vitro co-culture system, we show that human CD4+ and CD8+ T cells primed with a BCG derived peptide developed enhanced reactivity to its corresponding SARS-CoV-2 derived peptide. As expected, HLA differences between individuals meant that not all persons developed immunogenic responses to all 8 BCG derived peptides. Nevertheless, all of the 20 individuals that were primed with BCG derived peptides developed enhanced T cell reactivity to at least 7 of 8 SARS-CoV-2 derived peptides. These findings provide a mechanistic basis for the epidemiologic observation that BCG vaccination confers protection from COVID-19; and supports the use of BCG vaccination to induce cross-reactive SARS-CoV-2 specific T cell responses.
Role of asymptomatic COVID-19 cases in viral transmission: Findings from a hierarchical community contact network model1
Authors: Luo Tianyi , Cao Zhidong , Wang Yuejiao , Zeng Daniel Dajun , Zhang Qingpeng 
Published: November 2020

AbstractBackgroundAs part of on-going efforts to contain the COVID-19 pandemic, understanding the role of asymptomatic patients in the transmission system is essential to infection control. However, optimal approach to risk assessment and management of asymptomatic cases remains unclear.MethodsThis study involved a SEINRHD epidemic propagation model, constructed based on epidemiological characteristics of COVID-19 in China, accounting for the heterogeneity of social network. We assessed epidemic control measures for asymptomatic cases on three dimensions. Impact of asymptomatic cases on epidemic propagation was examined based on the effective reproduction number, abnormally high transmission events, and type and structure of transmission.ResultsManagement of asymptomatic cases can help flatten the infection curve. Tracking 75% of asymptomatic cases corresponds to an overall reduction in new cases by 34.3% (compared to tracking no asymptomatic cases). Regardless of population-wide measures, family transmission is higher than other types of transmission, accounting for an estimated 50% of all cases.ConclusionsAsymptomatic case tracking has significant effect on epidemic progression. When timely and strong measures are taken for symptomatic cases, the overall epidemic is not sensitive to the implementation time of the measures for asymptomatic cases.
Constructing spatial perception through self-touch
Authors: Cataldo A. , Dupin L. , Dempsey-Jones H. , Gomi H. , Haggard P. 
Published: November 2020

AbstractClassical accounts of spatial perception are based either on the topological layout of sensory receptors, or on implicit spatial information provided by motor commands. In everyday self-touch, as when stroking the left arm with the right hand, these elements are inextricably linked, meaning that tactile and motor contributions to spatial perception cannot readily be disentangled. Here, we developed a robot-mediated form of self-touch in order to decouple the spatial extent of active or passive movements from their tactile consequences. Participants judged the spatial extent of either the movement of the right hand, or of the resulting tactile stimulation to their left forearm. Across five experiments, we found bidirectional interference between motor and tactile information. Crucially, both directions of interference were stronger during active than passive movements. Thus, voluntary motor commands produced stronger integration of multiple signals relevant to spatial perception.
RepairSig: Deconvolution of DNA damage and repair contributions to the mutational landscape of cancer
Authors: Wojtowicz Damian , Hoinka Jan , Amgalan Bayarbaatar , Kim Yoo-Ah , Przytycka Teresa M. 
Published: November 2020

AbstractMany mutagenic processes leave characteristic imprints on cancer genomes known as mutational signatures. These signatures have been of recent interest regarding their applicability in studying processes shaping the mutational landscape of cancer. In particular, pinpointing the presence of altered DNA repair pathways can have important therapeutic implications. However, mutational signatures of DNA repair deficiencies are often hard to infer. This challenge emerges as a result of deficient DNA repair processes acting by modifying the outcome of other mutagens. Thus, they exhibit non-additive effects that are not depicted by the current paradigm for modeling mutational processes as independent signatures. To close this gap, we present RepairSig, a method that accounts for interactions between DNA damage and repair and is able to uncover unbiased signatures of deficient DNA repair processes. In particular, RepairSigwas able to replace three MMR deficiency signatures previously proposed to be active in breast cancer, with just one signature strikingly similar to the experimentally derived signature. As the first method to model interactions between mutagenic processes, RepairSigis an important step towards biologically more realistic modeling of mutational processes in cancer. The source code for RepairSigis publicly available athttps://github.com/ncbi/RepairSig.
Dynamics ofORF1abandNGene among hospitalized COVID-19 positive cohorts: A hospital based retrospective study
Authors: Loying Pojul , Sarma Vaishali , Hazarika Suranjana C. , Kataki Monjuri , Raja Dina , Medhi Divyashree , Dutta Ridip , Chena Achu , Daimary Divya , Choudhury Aakangkhita , Saikia Lahari 
Published: November 2020

1.AbstractObjectiveThe present study hospital based retrospective study aimed at investigating the dynamics of ORF1ab and N gene from hospitalized COVID-19 positive cohorts considering the Ct values of both genes.Study design and MethodologyRetrospective analyses of Ct values were done from 115 hospitalized COVID-19 positive patients in different time interval. Patients were admitted to the hospital either by RAT or/and RT-PCR and first RT-PCR testing were made after 9 days of incubation followed by testing in every 3 days of interval till negative, subsequently release of the patients.ResultsWe have looked into the dynamics of ORF1ab and N gene and found that N gene require longer duration of days with 12.68 (S.D.±3.24) to become negative than ORF1ab with 12.09 (S.D.±2.88) days and it differs significantly (p=0.012; p<0.05). The persistent of N gene found in 46 patients out of 115 (39.65%) to the succeeding reading after 3 days. We have also looked into the mean differences in the between N and ORF1ab genes every readings separately and found that there were no significant differences between the mean Ct value of ORF1ab and N gene except in the day 3 (p=0.015; p<0.05). Further, we have looked into the relationship of age and gender of patients with the duration of positivity; however we did not find any significant role.ConclusionIn COVID-19 hospital positive cohorts, the persistent of positivity of N gene is significantly for more duration than ORF1ab. As the SARS-CoV-2 is a new virus and study on it is evolving, so, exhaustive study is required on the dynamic of N gene positivity persistent in relation to the other pathophysiological parameters for the management and control of COVID-19.
Offering an Internet Survey Response Mode in a Flint Water Crisis Medicaid Population
Authors: Ford Sabrina , Oberst Kathleen , Ilardo Joan , An Hong Su , Jones Nicole , Hong Hyokyoung , Clark Karen , Luo Zhehui 
Published: November 2020

AbstractObjectiveTo examine the preferred response mode (internet, phone, paper)to a Medicaid enrollee survey.Data SourceData was obtained from survey responses for a sub-sample of Flint Water Crisis Medicaid Expansion Waiver enrollees (N=2584).Study DesignEnrollees were offered the choice of utilizing the internet, telephone, or mail to respond to a survey evaluating health services. Analyses were stratified by age, residency, race, and income. Chi-square was utilized to detect categorical differences.Principal FindingsThe majority (p<0.01) of participants responded by internet (55.46%), followed by mail (39.36%), and telephone (5.19%). Of those responding by internet, 75% used smart phones for connectivity. Weighted participation estimates for available survey modes showed variation by age, residence, race/ethnicity and poverty status. A smaller proportion (p<0.01) of ethnicities classified as Hispanic and Other used telephone participation compared to White or Black respondents.Respondents at 200% Federal Poverty Level (FPL) or higher used internet at greater rates than those below 200% FPL (p<0.01).ConclusionsOverall, this low-income population preferred the web-based response mode compared to paper or telephone, the variation by race and FPL suggests the continued presence of a digital divide in the population. Nevertheless, our findings revealed greater utilization of web-based tools for survey administration in vulnerable populations than was expected. This is a valuable finding that may inform future health programming and telehealth efforts particularly in the advent of COVID-19.What this study addsActive health care participation using internet connectivity is increasing and may be associated with improved quality and costs of health care services yet access and usage vary among populations.Research suggests that persons of low income and resources are unable to participate with internet based activities due to access and literacy issues that may further exacerbate health disparities.This study revealed enrollees of the Flint Michigan Section 1115 Demonstration utilized the internet for survey participation at a greater rate than responding by mail or phone.Finding that vulnerable populations have greater access to the internet via digital technology than assumed may expand opportunities to participate in their health care through health information portals and telehealth.
Targeting mitochondrial respiration and the BCL2 family in MYC-associated B-cell lymphoma
Authors: Donati Giulio , Ravà Micol , Filipuzzi Marco , Nicoli Paola , Cassina Laura , Verrecchia Alessandro , Doni Mirko , Rodighiero Simona , Parodi Federica , Boletta Alessandra , Vellano Christopher P. , Marszalek Joseph R. , Draetta Giulio F. , Amati Bruno 
Published: November 2020

AbstractMultiple molecular features, such as activation of specific oncogenes (e. g.MYC,BCL2) or a variety of gene expression signatures, have been associated with disease course in diffuse large B-cell lymphoma (DLBCL). Understanding the relationships between these features and their possible exploitation toward disease classification and therapy remains a major priority in the field. Here, we report that MYC activity in DLBCL is closely correlated with – and most likely a driver of – gene signatures related to Oxidative Phosphorylation (OxPhos). On this basis, we hypothesized that enzymes involved in Oxidative Phosphorylation, and in particular electron-transport chain (ETC) complexes, might constitute tractable therapeutic targets in MYC-associated lymphoma. Indeed, our data show that MYC sensitizes B-cells to IACS-010759, a selective inhibitor of ETC complex I. Mechanistically, IACS-010759 activates an ATF4-driven Integrated Stress Response (ISR), engaging the intrinsic apoptosis pathway through the transcription factor CHOP. In line with these findings, IACS-010759 shows synergy with the BCL2 inhibitor venetoclax against double-hit lymphoma (DHL), a high-grade form of DLBCL with concurrent activation ofMYCandBCL2. Similarly, in BCL2-negative lymphoma cell lines, inhibition of the BCL2-related protein Mcl-1 potentiates killing by IACS-010759. Altogether, ETC complex I inhibition engages the ISR to lower the apoptotic threshold in MYC-driven lymphomas and, in combination with select BCL2-family inhibitors, provides a novel therapeutic principle against this aggressive DLBCL subset.Statement of significanceThis work points to OxPhos as a key MYC-activated process and a tractable therapeutic target toward personalized treatment of high-grade DLBCL, providing strong context-dependent cooperation with BH3-mimetic compounds.
GEMC1-MCIDAS transcriptional program regulates multiciliogenesis in the choroid plexus and acts as a barrier to tumorigenesis
Authors: Li Qun , Han Zhiyuan , Singh Navleen , Terré Berta , Fame Ryann M. , Arif Uzayr , Page Thomas D. , Zahran Tasneem , Abdeltawab Ahmed , Huang Yuan , Cao Ping , Wang Jun , Lu Hao , Lidov Hart G.W. , Surendran Kameswaran , Wu Lizhao , Schüller Ulrich , Wechsler-Reya Robert J. , Lehtinen Maria K. , Roy Sudipto , Liu Zhongmin , Stracker Travis H. , Zhao Haotian 
Published: November 2020

AbstractMulticiliated cells (MCCs) in the brain include the ependymal cells and choroid plexus (CP) epithelial cells. The CP secretes cerebrospinal fluid that circulates within the ventricular system, driven by ependymal cilia movement. However, the mechanisms and functional significance of multiciliogenesis in the CP remain unknown. Deregulated oncogenic signals cause CP carcinoma (CPC), a rare but aggressive pediatric brain cancer. Here we show that aberrant NOTCH and Sonic Hedgehog signaling in mice drive tumors that resemble CPC in humans. NOTCH-driven CP tumors were monociliated, whereas disruption of the NOTCH complex restored multiciliation and decreased tumor growth. NOTCH suppressed multiciliation in tumor cells by inhibiting the expression of GEMC1 and MCIDAS, early regulators of multiciliogenesis. Consistently, GEMC1-MCIDAS function is essential for multiciliation in the CP, and is critical for correcting multiciliation defect in tumor cells by a NOTCH inhibitor. Disturbances to theGEMC1program are commonly observed in human CPCs characterized by solitary cilia. Consistently, CPC driven by deletion ofTrp53andRb1in mice exhibits a cilia deficit consequent to loss ofGemc1-Mcidasexpression. Taken together, these findings reveal a GEMC1-MCIDAS multiciliation program in the CP critical for inhibiting tumorigenesis, and it may have therapeutic implications for the treatment of CPC.
A solution to temporal credit assignment using cell-type-specific modulatory signals
Authors: Liu Yuhan Helena , Smith Stephen , Mihalas Stefan , Shea-Brown Eric , Sümbül Uygar 
Published: November 2020

AbstractAnimals learn and form memories by jointly adjusting the efficacy of their synapses. How they efficiently solve the underlying temporal credit assignment problem remains elusive. Here, we re-analyze the mathematical basis of gradient descent learning in recurrent spiking neural networks (RSNNs) in light of the recent single-cell transcriptomic evidence for cell-type-specific local neuropeptide signaling in the cortex. Our normative theory posits an important role for the notion of neuronal cell types and local diffusive communication by enabling biologically plausible and efficient weight update. While obeying fundamental biological constraints, including separating excitatory vs inhibitory cell types and observing connection sparsity, we trained RSNNs for temporal credit assignment tasks spanning seconds and observed that the inclusion of local modulatory signaling improved learning efficiency. Our learning rule puts forth a novel form of interaction between modulatory signals and synaptic transmission. Moreover, it suggests a computationally efficient learning method for bio-inspired artificial intelligence.