bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fabrication of ulcer-adhesive oral keratin hydrogel for gastric ulcer healing in a rat
Authors: Cheng Zhongjun , Qing Rui , Hao Shilei , Ding Yi , Yin Haimeng , Zha GuoDong , Chen Xiaoliang , Ji Jingou , Wang Bochu 
Published: March 2021

Abstract
Hydrogel has been used for in suit gastric ulcer therapy by stopping bleeding, separating from ulcer from gastric fluids and providing extracellular matrix scaffold for tissue regeneration, however, this treatment guided with endoscopic catheter in most cases. Here, we developed an oral keratin hydrogel to accelerate the ulcer healing without endoscopic guidance, which can specially adhere to the ulcer because of the high-viscosity gel formation on the wound surface in vivo. Approximately 50% of the ulcer-adhesive keratin hydrogel can resident in ethanol-treated rat stomach within 12 h, while approximately 18% of them maintained in health rat stomach in the same amount of time. Furthermore, Keratin hydrogels accelerated the ethanol-induced gastric ulcer healing by stopping the bleeding, preventing the epithelium cells from gastric acid damage, suppressing inflammation and promoting re-epithelization. The oral administration of keratin hydrogel in gastric ulcer treatment can enhance the patient compliance and reduce the gastroscopy complications. Our research findings reveal a promising biomaterial-based approach for treating gastrointestinal ulcers.
Small Words That Matter: Linguistic Style and Conceptual Disorganization in Untreated First-Episode Schizophrenia
Authors: Silva Angelica , Limongi Roberto , MacKinley Michael , Palaniyappan Lena 
Published: March 2021

AbstractThis study aimed to shed light on the linguistic style affecting the communication discourse in first-episode schizophrenia (FES) by investigating the analytic thinking index in relation to clinical scores of conceptual and thought disorganization (Positive and Negative Syndrome Scale, PANSS-P2 and Thought and Language Index, TLI). Using robust Bayesian modeling, we report three major findings: (1) FES subjects showed reduced analytic thinking, exhibiting a less categorical linguistic style than healthy control (HC) subjects (Bayes factor, BF10 &gt; 1000), despite using the same proportion of function and content words as HCs; (2) the lower the analytic thinking score, the higher the symptoms scores of conceptual disorganization (PANSS-P2, BF = 22.66) and global disorganization of thinking (TLI, BF10 = 112.73); (3) the linguistic style is a better predictor of conceptual disorganization than the cognitive measure of processing speed in schizophrenia (SZ). These findings provide an objectively detectable linguistic style with a focus on Natural Language Processing Analytics of transcribed speech samples of patients with SZ that require no clinical judgment. These findings also offer a crucial insight into the primacy of linguistic structural disruption in clinically ascertained disorganized thinking in SZ. Our work contributes to an emerging body of literature on the psychopathology of SZ using a first-order lexeme-level analysis and a hypothesis-driven approach. At a utilitarian level, this has implications for improving educational and social outcomes in patients with SZ.
Intrahost speciations and host switches played an important role in the evolution of herpesviruses
Authors: Brito Anderson F , Baele Guy , Nahata Kanika D , Grubaugh Nathan D , Pinney John W 
Published: March 2021

Abstract
In times when herpesvirus genomic data were scarce, the cospeciation between these viruses and their hosts was considered to be common knowledge. However, as more herpesviral sequences were made available, tree reconciliation analyses started to reveal topological incongruences between host and viral phylogenies, indicating that other cophylogenetic events, such as intrahost speciation and host switching, likely played important roles along more than 200 million years of evolutionary history of these viruses. Tree reconciliations performed with undated phylogenies can identify topological differences, but offer insufficient information to reveal temporal incongruences between the divergence timing of host and viral species. In this study, we performed cophylogenetic analyses using time-resolved trees of herpesviruses and their hosts, based on careful molecular clock modelling. This approach enabled us to infer cophylogenetic events over time and also integrate information on host biogeography to better understand host–virus evolutionary history. Given the increasing amount of sequence data now available, mismatches between host and viral phylogenies have become more evident, and to account for such phylogenetic differences, host switches, intrahost speciations and losses were frequently found in all tree reconciliations. For all subfamilies in Herpesviridae, under all scenarios we explored, intrahost speciation and host switching were more frequent than cospeciation, which was shown to be a rare event, restricted to contexts where topological and temporal patterns of viral and host evolution were in strict agreement.
New SARS-CoV-2 lineages could evade CD8+ T-cells response
Authors: Pretti Marco Antonio M. , Galvani Rômulo G. , Farias Alessandro S , Boroni Mariana 
Published: March 2021

AbstractBackgroundMany SARS-CoV-2 variants of concern have emerged since the Covid-19 outburst, notably the lineages detected in the UK, South Africa, and Brazil. Their increased transmissibility and higher viral load put them in the spotlight. Much has been investigated on the ability of those new variants to evade antibody recognition. However, not enough attention has been given to pre-existing and induced SARS-CoV-2-specific CD8+ T cell responses during the natural course of infection by new lineages.MethodsIn this work, we investigated the SARS-CoV-2-specific CD8+ T cell epitopes from the main variants of concern and the potential of associated mutations to trigger or hinder CD8+ T-cells response. We also estimated the population’s coverage of these different lineages, considering peptide binding predictions to class I HLA alleles from 29 countries to investigate differences in the fraction of individuals expected to respond to a given epitope set from new and previous lineages.ResultsWe observed a lower populational coverage for 20B/S.484K (P.2 lineage) in contrast to an increased coverage found for 20H/501Y.V2 (B.1.351 Lineage) and 20J/501Y.V3 (P.1 lineage) compared to a reference lineage. Moreover, mutations such as Spike N501Y and Nucleocapsid T205I were predicted to have an overall higher affinity through HLA-I than the reference sequence.ConclusionsIn summary, the data in this work provided evidence for the existence of potentially immunogenic and conserved epitopes across new SARS-CoV-2 variants, but also highlights the reduced populational’s coverage for the Brazilian lineage P.2, suggesting its potential to evade from CD8+ T-cell responses. Our results also may guide efforts to characterize and validate relevant peptides to trigger CD8+ T-cell responses, and design new universal T-cell-inducing vaccine candidates that minimize detrimental effects of viral diversification and at the same time induce responses to a broad human population.
COVID-19 Vaccine Acceptance and Hesitancy in Low and Middle Income Countries, and Implications for Messaging
Authors: Solís Arce Julio S. , Warren Shana S. , Meriggi Niccoló F. , Scacco Alexandra , McMurry Nina , Voors Maarten , Syunyaev Georgiy , Malik Amyn Abdul , Aboutajdine Samya , Armand Alex , Asad Saher , Augsburg Britta , Bancalari Antonella , Nyqvist Martina Björkman , Borisova Ekaterina , Bosancianu Constantin Manuel , Cheema Ali , Collins Elliott , Farooqi Ahsan Zia , Fracchia Mattia , Guariso Andrea , Hasanain Ali , Kamwesigye Anthony , Kreps Sarah , Levine Madison , Littman Rebecca , Platas Melina , Ramakrishna Vasudha , Shapiro Jacob N. , Svensson Jakob , Vernot Corey , Vicente Pedro C. , Weissinger Laurin B , Zhang Baobao , Karlan Dean , Callen Michael , Teachout Matthieu , Humphreys Macartan , Omer Saad B. , Mobarak Ahmed Mushfiq 
Published: March 2021

AbstractWe analyze COVID-19 vaccine acceptance across 15 survey samples covering ten low- and middle-income countries (LMICs) in Asia, Africa, and South America, Russia (an upper-middle-income country), and the United States, using survey responses from 44,260 individuals. We find considerably higher willingness to take a COVID-19 vaccine in LMIC samples (80% on average) compared to the United States (65%) and Russia (30%). Vaccine acceptance was primarily explained by an interest in personal protection against COVID-19, while concern about side effects was the most commonly expressed reason for reluctance. Health workers were the most trusted sources of information about COVID-19 vaccines. Our findings suggest that prioritizing vaccine distribution to LMICs should yield high returns in promoting global immunization coverage, and that vaccination campaigns in these countries should focus on translating acceptance into uptake. Messaging highlighting vaccine efficacy and safety, delivered by healthcare workers, may be most effective in addressing remaining hesitancy.
Spatial Prevalence and Determinants of Malaria among under-five Children in Ghana
Authors: Ejigu Bedilu Alamirie , Wencheko Eshetu 
Published: March 2021

AbstractIn Ghana malaria is an endemic disease and the incidence of malaria still accounts for 38.0% of all outpatient attendance with the most vulnerable groups being children under 5 years of age. In order to alleviate this problem, it is essential to design geographically targeted and cost-effective intervention mechanisms guided by up-to-date and reliable data and maps that show the spatial prevalence of the disease. The 2016 Ghana Malaria Indicator Survey data (N = 2,910 under-five children) were analyzed using model-based geostatistical methods with the two objectives to: (1) explore individual-, household-, and community-level determinant variables associated with malaria illness in U5 children, and (2) produce prevalence maps of malaria across the study locations in the country. The overall weighted prevalence of malaria by microscopy blood smear and rapid diagnostic tests were 20.63% (with 95% CI: 18.85% - 22.53%) and 27.82% (with 95% CI: 25.81% - 29.91%), respectively. Across regions of Ghana, the prevalence of malaria ranges from 5% in Greater Accra to 31% in Eastern region. Malaria prevalence was higher in rural areas, increased with child age, and decreased with better household wealth index and higher level of mother’s education. Given the high prevalence of childhood malaria observed in Ghana, there is an urgent need for effective and efficient public health interventions in hot spot areas. The determinant variables of malaria infection that have been identified in this study as well as the maps of parasitaemia risk could be used in malaria control program implementation to define priority intervention areas.
COVID-19 vaccine hesitancy among undergraduate medical students: results from a nationwide survey in India
Authors: Jain Jyoti , Saurabh Suman , Goel Akhil Dhanesh , Gupta Manoj Kumar , Bhardwaj Pankaj , Raghav Pankaja Ravi 
Published: March 2021

SummaryCOVID-19 vaccine was launched in India on 16 January 2021, prioritizing health care workers which included medical students. We aimed to assess vaccine hesitancy and factors related to it among undergraduate medical students in India. An online questionnaire was filled by 1068 medical students across 22 states and union territories of India from 2 February – 7 March 2021. Vaccine hesitancy was found among 10.6%. Concern regarding vaccine safety and efficacy, hurried testing of vaccines prior to launch and lack of trust in government agencies predicted COVID-19 vaccine hesitancy. Risk perception regarding contracting COVID-19 vaccine reduced COVID-19 vaccine hesitancy as well as hesitation in participating in COVID-19 vaccine trials. Choosing between the two available vaccines (Covishield and Covaxin) was considered important by medical students both for themselves and their future patients. Covishield was preferred to Covaxin by students. Majority of those willing to take the COVID-19 vaccine felt that it was important for them to resume their clinical posting, face-to-face classes and get their personal life back on track. Around three-fourths medical students viewed that COVID-19 vaccine should be made mandatory for both health care workers and international travellers. Prior adult vaccination didn’t have an effect upon COVID-19 vaccine hesitancy. Targeted awareness campaigns, regulatory oversight of vaccine trials and public release of safety and efficacy data and trust building activities could further reduce COVID-19 vaccine hesitancy among medical students.
Deep brain stimulation in the bed nucleus of the stria terminalis: a symptom provocation study in patients with obsessive-compulsive disorder
Authors: Luyck Kelly , Bervoets Chris , Deblieck Choi , Nuttin Bart , Luyten Laura 
Published: March 2021

AbstractBackgroundDeep brain stimulation (DBS) is an emerging therapy for treatment-resistant obsessive-compulsive disorder (OCD), and several targets for electrode implantation and contact selection have been proposed, including the bed nucleus of the stria terminalis (BST). Selecting the active electrode contacts (patients typically have four to choose from in each hemisphere), and thus the main locus of stimulation, can be a taxing process. Here, we investigated whether contact selection based purely on their neuroanatomical position in the BST is a worthwhile approach. For the first time, we also compared the effects of uni- versus bilateral BST stimulation.MethodsNine OCD patients currently receiving DBS participated in a double-blind, randomized symptom provocation study to compare no versus BST stimulation. Primary outcomes were anxiety and mood ratings in response to disorder-relevant trigger images, as well as ratings of obsessions, compulsions, tendency to avoid and overall wellbeing. Furthermore, we asked whether patients preferred the electrode contacts in the BST over their regular stimulation contacts as a new treatment setting after the end of the task.ResultsWe found no statistically significant group differences between the four conditions (no, left, right and bilateral BST stimulation). Exploratory analyses, as well as follow-up data, did indicate that (bilateral) bipolar stimulation in the BST was beneficial for some patients, particularly for those who had achieved unsatisfactory effects through the typical contact selection procedure.ConclusionsDespite its limitations, this study suggests that selection of stimulation contacts in the BST is a viable option for DBS in treatment-resistant OCD patients.
Mitochondrial Phenotypes Distinguish Pathogenic MFN2 Mutations by Pooled Functional Genomics Screen
Authors: Yenkin Alex L. , Bramley John C. , Kremitzki Colin L. , Waligorski Jason E. , Liebeskind Mariel J. , Xu Xinyuan E. , Vakaki Maria A. , Chandrasekaran Vinay D. , Mitra Robi D. , Milbrandt Jeffrey D. , Buchser William J. 
Published: March 2021

AbstractMost human genetic variation is classified as VUS - variants of uncertain significance. While advances in genome editing have allowed innovation in pooled screening platforms, many screens deal with relatively simple readouts (viability, fluorescence) and cannot identify the complex cellular phenotypes that underlie most human diseases. In this paper, we present a generalizablefunctional genomicsplatform that combines high-content imaging, machine learning, and microraft isolation in a new method termed “Raft-Seq”. We highlight the efficacy of our platform by showing its ability to distinguish pathogenic point mutations of the mitochondrial regulatorMFN2, even when the cellular phenotype is subtle. We also show that our platform achieves its efficacy using multiple cellular features, which can be configured on-the-fly. Raft-Seq enables a new way to perform pooled screening on sets of mutations in biologically relevant cells, with the ability to physically capture any cell with a perturbed phenotype and expand it clonally, directly from the primary screen.Graphical AbstractHere, we address the need to evaluate the impact of numerous genetic variants. This manuscript depicts the methods of using machine learning on a biologically relevant phenotype to predict specific point mutations, followed by physically capturing those mutated cells.
GWAS associated Variants, Non-genetic Factors, and Transient Transcriptome in Multiple Sclerosis Etiopathogenesis: a Colocalization Analysis
Authors: Umeton Renato , Bellucci Gianmarco , Bigi Rachele , Romano Silvia , Buscarinu Maria Chiara , Reniè Roberta , Rinaldi Virginia , Umeton Raffaella Pizzolato , Morena Emanuele , Romano Carmela , Mechelli Rosella , Salvetti Marco , Ristori Giovanni 
Published: March 2021

AbstractA clinically actionable understanding of multiple sclerosis (MS) etiology goes through GWAS interpretation, prompting research on new gene regulatory models. We previously suggested a stochastic etiologic model where small-scale random perturbations could reach a threshold for MS development. The recently described mapping of the transient transcriptome (TT), including intergenic and intronic RNAs, seems appropriate to verify this model through a rigorous colocalization analysis. We show that genomic regions coding for the TT were significantly enriched for MS-associated GWAS variants and DNA binding sites for molecular transducers mediating putative, non-genetic, etiopathogenetic factors for MS (e.g., vitamin D deficiency, Epstein Barr virus latent infection, B cell dysfunction). These results suggest a model whereby TT-coding regions are hotspots of convergence between genetic ad non-genetic factors of risk/protection for MS, and plausibly for other complex disorders. Our colocalization analysis also provides a freely available data resource (www.mscoloc.com) for future research on MS transcriptional regulation.
Ensemble Switching Unveils a Kinetic Rheostat Mechanism of the Eukaryotic Thiamine Pyrophosphate Riboswitch
Authors: Ma Junyan , Saikia Nabanita , Godar Subash , Hamilton George L. , Ding Feng , Alper Joshua , Sanabria Hugo 
Published: March 2021

ABSTRACTThiamine pyrophosphate (TPP) riboswitches regulate thiamine metabolism by inhibiting the translation of enzymes essential to thiamine synthesis pathways upon binding to thiamine pyrophosphate in cells across all domains of life. Recent work on theArabidopsis thalianaTPP riboswitch suggests a multi-step TPP binding process involving multiple riboswitch conformational ensembles and that Mg2+dependence underlies the mechanism of TPP recognition and subsequent transition to the translation-inhibiting state of the switching sequence followed by changes in the expression platform. However, details of the relationship between TPP riboswitch conformational changes and interactions with TPP and Mg2+in the aptamer domain constituting this mechanism are unknown. Therefore, we integrated single-molecule multiparameter fluorescence and force spectroscopy with atomistic molecular dynamics simulations and found that conformational transitions within the aptamer domain associated with TPP and Mg2+ligand binding occurred between at least five different ensembles on timescales ranging from μs to ms. These dynamics are at least an order of magnitude faster than folding and unfolding kinetics associated with translation-state switching in the switching sequence. Moreover, we propose that two pathways exist for ligand recognition. Together, our results suggest a dynamic ensemble switching of the aptamer domain that may lead to the translation-inhibiting state of the riboswitch. Additionally, our results suggest that multiple configurations could enable inhibitory tuning manifested through ligand-dependent changes via ensemble switching and kinetic rheostat-like behavior of theArabidopsis thalianaTPP riboswitch.
DNA origami patterning of synthetic T cell receptors reveals spatial control of the sensitivity and kinetics of signal activation
Authors: Dong Rui , Aksel Tural , Chan Waipan , Germain Ronald N. , Vale Ronald D. , Douglas Shawn M. 
Published: March 2021

SUMMARYT cell receptor clustering plays a key role in triggering cell activation, but the relationship between the spatial configuration of clusters and elicitation of downstream intracellular signals remains poorly understood. We developed a DNA-origami-based system that is easily adaptable to other cellular systems and enables rich interrogation of responses to a variety of spatially defined inputs. Using a chimeric antigen receptor (CAR) T cell model system with relevance to cancer therapy, we studied signaling dynamics at single cell resolution. We found that the spatial arrangement of receptors determines the ligand density threshold for triggering and encodes the temporal kinetics of signaling activities. We also showed that signaling sensitivity of a small cluster of high-affinity ligands is enhanced when surrounded by non-stimulating low-affinity ligands. Our results suggest that cells measure spatial arrangements of ligands and translates that information into distinct signaling dynamics, and provide insights into engineering new immunotherapies.
Familial thyroid follicular cell carcinomas in a large number of Dutch German longhaired pointers
Authors: Yu Yun , Krupa Adriana , Keesler Rebekah I. , Grinwis Guy C. M. , de Ruijsscher Mariska , de Vos Johan , Groenen Martien A. M. , Crooijmans Richard P. M. A. 
Published: March 2021

AbstractThyroid carcinomas originating from follicular cells of the thyroid gland occur in both humans and dogs and they have highly similar histomorphologic patterns. In dogs, thyroid carcinomas have not been extensively investigated, especially concerning the familial origin of thyroid carcinomas. Here we report familial thyroid follicular cell carcinomas confirmed by histology in 54 Dutch origin German longhaired pointers. From the pedigree, 45 of 54 histopathologically confirmed cases are closely related to a pair of first-half cousins in the past, indicating a familial disease. In addition, genetics contributed more to the thyroid follicular cell carcinoma than other factors by an estimated heritability of 0.62 based on pedigree. The age of diagnosis ranged between 4.5 and 13.5 years, and 76% of cases were diagnosed before 10 years of age, implying an early onset of disease. We observed a significant higher pedigree-based inbreeding coefficient in the affected dogs (meanF0.23) compared to unaffected dogs (meanF0.14), suggesting the contribution of inbreeding to tumour development. The unique occurrence of familial thyroid follicular cell carcinoma in this dog population and the large number of affected dogs make this population an important model to identify the genetic basis of familial thyroid follicular cell carcinoma in this breed and may contribute to the research into pathogenesis, prevention and treatment in humans.