bluuebunny/crossref_metadata_2025_split huggingface dataset:
A potent synthetic nanobody targets RBD and protects mice from SARS-CoV-2 infection
Authors: Li Tingting , Cai Hongmin , Yao Hebang , Zhou Bingjie , Zhang Ning , Gong Yuhuan , Zhao Yapei , Shen Quan , Qin Wenming , Hutter Cedric A.J. , Lai Yanling , Kuo Shu-Ming , Bao Juan , Lan Jiaming , Seeger Markus A. , Wong Gary , Bi Yuhai , Lavillette Dimitri , Li Dianfan 
Published: June 2020

ABSTRACTSARS-CoV-2, the causative agent of COVID-191, recognizes host cells by attaching its receptor-binding domain (RBD) to the host receptor ACE22–7. Neutralizing antibodies that block RBD-ACE2 interaction have been a major focus for therapeutic development8–18. Llama-derived single-domain antibodies (nanobodies, ∼15 kDa) offer advantages including ease of production and possibility for direct delivery to the lungs by nebulization19, which are attractive features for bio-drugs against the global respiratory disease. Here, we generated 99 synthetic nanobodies (sybodies) by in vitro selection using three libraries. The best sybody, MR3 bound to RBD with high affinity (KD = 1.0 nM) and showed high neutralization activity against SARS-CoV-2 pseudoviruses (IC50 = 0.40 μg mL−1). Structural, biochemical, and biological characterization of sybodies suggest a common neutralizing mechanism, in which the RBD-ACE2 interaction is competitively inhibited by sybodies. Various forms of sybodies with improved potency were generated by structure-based design, biparatopic construction, and divalent engineering. Among these, a divalent MR3 conjugated with the albumin-binding domain for prolonged half-life displayed highest potency (IC50 = 12 ng mL−1) and protected mice from live SARS-CoV-2 challenge. Our results pave the way to the development of therapeutic nanobodies against COVID-19 and present a strategy for rapid responses for future outbreaks.
Mathematical estimation of COVID-19 prevalence in Latin America
Authors: Matabuena Marcos , Rodríguez-Mier Pablo , Meijide-García Carlos , Leborán Víctor , Gude Francisco 
Published: June 2020

AbstractAfter the rapid spread with severe consequences in Europe and China, the SARS-CoV-2 virus is now manifesting itself in more vulnerable countries, including those in Latin America. In order to guide political decision-making via epidemiological criteria, it is crucial to assess the real impact of the epidemic. However, the use of large-scale population testing is unrealistic or not feasible in some countries. Based on a newly developed mathematical model, we estimated the seroprevalence of SARS-CoV-2 in Latin American countries. The results show that the virus spreads unevenly across countries. For example, Ecuador and Brazil are the most affected countries, with approximately 3% of the infected population. Currently, the number of new infections is increasing in all countries examined, with the exception of some Caribbean countries as Cuba. Moreover, in these countries, the peak of newly infected patients has not yet been reached.
Assessment of Experiences of Preventive Measures Practice including Vaccination History and Health Education among Umrah Pilgrims in Saudi Arabia, 1440H-2019
Authors: Tobaiqy Mansour , Almudarra Sami S. , M.Shams Manal , Amer Samar A. , F.Alcattan Mohamed , H.Alhasan Ahmed 
Published: June 2020

AbstractBackgroundAnnually, approximately 10 million Umrah pilgrims travel to the Kingdom of Saudi Arabia for Umrah from more than 180 countries. This event presents major challenges for the Kingdom’s public health sector, which strives to decrease the burden of infectious diseases and to adequately control its spread.Aims of the studyThe aims of the study were to assess the experiences of preventive measures practice, including vaccination history and health education, among Umrah pilgrims in Saudi Arabia.MethodsA cross sectional survey administered to a randomly selected group of pilgrims by the research team members from February to the end of April 2019 at the departure lounge at King Abdul Aziz International airport, Jeddah city. The questionnaire was comprised of questions on the following factors: sociodemographic information, level of education, history of vaccinations and chronic illnesses, whether the pilgrim has received any health education and orientation prior to coming Saudi Arabia or on their arrival, and their experiences with preventive medicine.ResultsPilgrims (n=1012) of 48 nationalities completed the survey and were reported in this study. Chronic diseases (n=230) were reported among pilgrims, with hypertension being the most reported morbidity (n=124, 53.9%). The majority of pilgrims had taken immunization prior to travel to Saudi Arabia, and the most commonly reported immunizations were meningitis (n=567, 56%), influenza (n=460, 45.5%), and Hepatitis B virus vaccinations (n=324, 32%); however, 223(22%) had not received any vaccinations prior to travel, including meningitis vaccine, which is mandatory in Saudi Arabia. 305 pilgrims (30.1%) had reported never using face masks in crowded areas; however, 63.2% reported lack of availability of these masks.The majority of participants had received health education on preventive measures, including hygienic aspects (n=799, 78.9%) mostly in their home countries (n=450, 56.3%). A positive association was found between receiving health education and practicing of preventive measures, such as wearing masks in crowded areas (P= 0.04) and other health practice scores (P= 0.02).ConclusionAlthough the experiences of the preventive measures among pilgrims in terms of health education, vaccinations, and hygienic practices were overall positive, this study identified several issues with the following preventive measures: immunizations particularly meningitis vaccine and using face masks in crowded areas.Further studies are required to develop a health education module to promote comprehensive preventive measures for pilgrims.
Rapid characterization of the propagation of COVID-19 in different countries
Authors: Vargas Patricio , Allende Sebastián , Vogel Eugenio E. , Kobe Sigismund 
Published: June 2020

ABSTRACTBACKGROUNDCOVID-19 has spread rapidly, and there are still many characteristics of this new disease to be unveiled. We propose a simple method to calculate a “figure of merit” FC to provide an early characterization of the disease status in country C.METHODSWe use mathematical tools to adjust a Gaussian function to the daily increase of infected patients. Maximum value and full width half maximum of the Gaussian are characteristics of the development of the development of the pandemic in each country. These parameters are supplemented by the testing volume and the mortality rate to produce just one characterizing parameter: FC. In addition, the stability of the Gaussian fits was calculated within an entire week towards the end of the study period. Seventeen different countries were fully considered, while others are considered when discussing particular properties. Data employed is publically available.FINDINGSFitted Gaussian functions render effective information about the development of COVID-19. The number of critical days vary between 11 (South Korea) and 52 (Mexico). FC varies between 1 (Australia) and 899 (Mexico). The epidemic appears stabilized in some countries and unstable in others. Some large countries are experiencing fast development of the propagation of the disease with high FC. A correlation between low (high) values of the mortality rate (and to some extent FC) and the presence (absence) of BCG vaccination is exposed.INTERPRETATIONThe adjustment of a Gaussian to daily data of COVID-19 in each country reveals the different propagation dynamics, properly characterized by the parameters proposed here. Testing plays a clear role to control the spread of the disease. Mortality rate spans more than one order of magnitude and is somewhat related to permanent massive BCG vaccination. The figure of merit, FC, introduced here spans more than 2 orders of magnitude which makes it a useful indicator to quickly find out the status of the pandemics in each territory. Geography plays a role: low population density and isolated countries can be efficient in controlling the spread of the disease.HIGHLIGHTSAn easy-to-evaluate parameter is defined to rapidly establish the status of the evolution of COVID-19 in any given territory. 17 countries in 4 continents are chosen to apply it and compare different evolutions.The parameter or figure of merit (FC) is dynamic: it combines testing, mortality rate, and characteristics of the Gaussian function that fits the new daily contagions.FC spans more than two orders of magnitude which makes it a very sensitive indicator to promptly detect second waves or local outbreaks.It is found that countries with massive BCG vaccination present low COVID-19 mortality rates and low values for FC.
Population-scale Longitudinal Mapping of COVID-19 Symptoms, Behavior, and Testing Identifies Contributors to Continued Disease Spread in the United States
Authors: Allen William E. , Altae-Tran Han , Briggs James , Jin Xin , McGee Glen , Shi Andy , Raghavan Rumya , Kamariza Mireille , Nova Nicole , Pereta Albert , Danford Chris , Kamel Amine , Gothe Patrik , Milam Evrhet , Aurambault Jean , Primke Thorben , Li Weijie , Inkenbrandt Josh , Huynh Tuan , Chen Evan , Lee Christina , Croatto Michael , Bentley Helen , Lu Wendy , Murray Robert , Travassos Mark , Coull Brent A. , Openshaw John , Greene Casey S. , Shalem Ophir , King Gary , Probasco Ryan , Cheng David R. , Silbermann Ben , Zhang Feng , Lin Xihong 
Published: June 2020

Summary ParagraphDespite social distancing and shelter-in-place policies, COVID-19 continues to spread in the United States. A lack of timely information about factors influencing COVID-19 spread and testing has hampered agile responses to the pandemic. We developed How We Feel, an extensible web and mobile application that aggregates self-reported survey responses, to fill gaps in the collection of COVID-19-related data. How We Feel collects longitudinal and geographically localized information on users’ health, behavior, and demographics. Here we report results from over 500,000 users in the United States from April 2, 2020 to May 12, 2020. We show that self-reported surveys can be used to build predictive models of COVID-19 test results, which may aid in identification of likely COVID-19 positive individuals. We find evidence among our users for asymptomatic or presymptomatic presentation, as well as for household and community exposure, occupation, and demographics being strong risk factors for COVID-19. We further reveal factors for which users have been SARS-CoV-2 PCR tested, as well as the temporal dynamics of self-reported symptoms and self-isolation behavior in positive and negative users. These results highlight the utility of collecting a diverse set of symptomatic, demographic, and behavioral self-reported data to fight the COVID-19 pandemic.
Clinical, dietary, and psychosocial effectiveness of interdisciplinary care in child and juvenile obesity
Authors: Menezes Carlos Alberto , Vasconcelos Rayzza Santos 
Published: June 2020

ABSTRACTThe aim of this study is to evaluate the effectiveness of interdisciplinary care in modifying anthropometric clinical parameters (BMI and waist circumference), psychosocial profile and eating behavior in a group of children and adolescents with obesity. This is a clinical study involving 200 children and adolescents with obesity who are participants of the “Serviço de Medicina Preventiva” program, and the “Centro de Especialidades Médicas de Crianças e Adolescentes” both in Aracaju, Sergipe, Brazil. At the end of the interdisciplinary intervention, there was a decrease in the number of hours devoted to electronic games and television and an increase in physical activity, which was associated with a reduction in reports of dissatisfaction and symptoms of depression. In addition, the sadness and prejudice related to obesity suffered at school and in the family environment were also attenuated, despite the percentage increase in the anxiety indicator. Regarding the anthropometric measurement, there was a reduction in body mass index, waist circumference, in caloric consumption. It is concluded that interdisciplinary programs are an effective strategy to reduce the negative repercussions of obesity in the daily lives of obese children and adolescents, as there were improvements in anthropometric parameters, in addition to psychosocial and dietary aspects.RESUMOO objetivo deste estudo é avaliar a eficácia do atendimento interdisciplinar na modificação de parâmetros clínicos antropométricos (IMC e circunferência da cintura), perfil psicossocial e comportamento alimentar em um grupo de crianças e adolescentes com obesidade. Trata-se de um estudo clínico envolvendo 200 crianças e adolescentes com obesidade participantes do programa “Serviço de Medicina Preventiva” e do “Centro de Especialidades Médicas de Crianças e Adolescentes”, ambos em Aracaju, Sergipe, Brasil. Ao final da intervenção interdisciplinar, houve uma diminuição no número de horas dedicadas a jogos eletrônicos e televisão e um aumento na atividade física, o que foi associado à redução nos relatos de insatisfação e sintomas de depressão. Além disso, a tristeza e o preconceito relacionados à obesidade sofrida na escola e no ambiente familiar também foram atenuados, apesar do aumento percentual no indicador de ansiedade. Em relação à medida antropométrica, houve redução do índice de massa corporal, circunferência da cintura e consumo calórico. Conclui-se que os programas interdisciplinares são uma estratégia eficaz para reduzir as repercussões negativas da obesidade no cotidiano de crianças e adolescentes obesos, pois houve melhorias nos parâmetros antropométricos, além de aspectos psicossociais e alimentares.
Implications of the reverse associations between obesity prevalence and coronavirus disease (COVID-19) cases and related deaths in the United States
Authors: Zhang Ning , Cordeiro Lorraine S. , Liu Zhenhua 
Published: June 2020

AbstractThe Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that was most recently discovered, quickly evolved into a global pandemic. Studies suggested that obesity was a major risk factor for its hospitalization and severity of symptoms. This study investigated the associations between obesity prevalence with overall COVID-19 cases and related deaths across states in the United States. General regression and Chi-square tests were used to examine those associations. The analyses indicated that obesity prevalence (%) across states were negatively associated with COVID-19 cases (p= 0.0448) and related deaths (p= 0.0181), with a decrease of 158 cases/100K population and 13 deaths/100K for every 5% increase of the obesity prevalence. When the states were divided based on the median of obesity prevalence (30.9%) into a group of states with low obesity prevalence and a group with high obesity prevalence, both the cases (671 vs 416 cases/100k population) and deaths (39 vs 21 deaths/100k population) were significantly different (p< 0.001) across groups. These findings provided important information for the relationship between the dual pandemic threats of obesity and COVID-19. These results should not currently be considered as an indication that obesity is a protective factor for COVID-19, and would rather be used as a warning of the public advice that obese people is more vulnerable to COVID-19 infection, which may lead to a false safety message probably given to people with normal body weight.
A new bioinformatic tool to interpret metagenomics / metatranscriptomics results based on the geometry of the clustering network and its differentially gene ontologies (GANGO)
Authors: Monleon-Getino Antonio , Paytuví-Gallart Andreu , Sanseverino Walter , Méndez Javier 
Published: June 2020

AbstractHigh-throughput experimental techniques, such as metagenomics or metatranscriptomics, produce large amounts of data, which interpretation and conversion into understandable knowledge can be challenging and out of reach. We present GANGO, a new algorithm based on the ecological concept of consortium (groups biologically connected) and by using clustering network analysis, gene ontologies and powerful hypothesis test allows the identification and interpretation of complex ecological networks, allowing the identification of the relationship between taxa/genes, the number of groups, their relations and their functionalities using the annotated genes of an organism in a database (e.g. UniProt or Ensembl). Three examples of the use of GANGO are shown: a simulated mixture of fungi and bacteria, alterations in soil fungi communities after a diesel-oil spill and genomic changes inSaccharomyces cerevisaedue to abiotic stress.
Sentinelp16INK4a+ cells in the basement membrane form a reparative niche in the lung
Authors: Reyes de Mochel Nabora , Cheong Ka Neng , Cassandras Monica , Wang Chaoqun , Krasilnikov Maria , Matatia Peri , Molofsky Ari , Campisi Judith , Peng Tien 
Published: June 2020

AbstractSenescent cells are recognized drivers of aging-related decline in organ function, but deciphering the biology of senescencein vivohas been hindered by the paucity of tools to track and isolate senescent cells in tissues1–4. Deleting senescent cells from transgenic murine models have demonstrated therapeutic benefits in numerous age-related diseases5–11, but the identity, behavior, and function of the senescent cells deletedin vivoremain elusive. We engineered an ultra-sensitive reporter ofp16INK4a, a biomarker of senescence12, to isolate and trackp16INK4a+ cellsin vivo. Surprisingly,p16INK4a+ mesenchymal cells appear in the basement membrane adjacent to epithelial progenitors in the lung shortly after birth, and these cells demonstrate senescent characteristicsin vivoandex vivo. Transcriptomic analysis ofp16INK4a+ mesenchymal cells from non-aged lungs demonstrates a transition to a secretory phenotype upon airway epithelial injury. Heterotypic 3D organoid assays show that injuredp16INK4a+ mesenchymal cells enhance epithelial progenitor proliferation, and we identified EREG as a novel airway progenitor mitogen produced by the secretoryp16INK4a+ mesenchymal cells. Mesenchymal-specific deletion of thep16INK4agene abrogates features of senescencein vivo, but also attenuates normal epithelial repair. Thus,p16INK4a+ mesenchymal cells can act as sentinels for the airway epithelial stem cell niche, poised to transition to a senescence-associated secretory phenotype to support barrier repair. Our data identify possible cellular targetsin vivofor a rapidly growing list of senolytic therapies, but also raises important questions about the hidden cost of targeting senescent cells present in normal organs.
SPECIFIC ECTODERMAL ENHANCERS CONTROL THE EXPRESSION OFHoxcGENES IN DEVELOPING MAMMALIAN INTEGUMENTS
Authors: Fernandez-Guerrero Marc , Yakushiji-Kaminatsui Nayuta , Lopez-Delisle Lucille , Zdral Sofía , Darbellay Fabrice , Perez-Gomez Rocío , Bolt Christopher Chase , Sanchez-Martin Manuel A. , Duboule Denis , Ros Maria A. 
Published: June 2020

AbstractVertebrateHoxgenes are key players in the establishment of structures during the development of the main body axis. Subsequently, they play important roles either in organizing secondary axial structures such as the appendages, or during homeostasis in postnatal stages and adulthood. Here we set up to analyze their elusive function in the ectodermal compartment, using the mouse limb bud as a model. We report that theHoxCgene cluster was globally co-opted to be transcribed in the distal limb ectoderm, where it is activated following the rule of temporal colinearity. These ectodermal cells subsequently produce various keratinized organs such as nails or claws. Accordingly, deletion of theHoxCcluster led to mice lacking nails (anonychia) and also hairs (alopecia), a condition stronger than the previously reported loss of function ofHoxc13, which is the causative gene of the ectodermal dysplasia 9 (ECTD9) in human patients. We further identified two ectodermal, mammalian-specific enhancers located upstream of theHoxCgene cluster, which act synergistically to regulateHoxcgene expression in the hair and nail ectodermal organs. Deletion of these regulatory elements alone or in combination revealed a strong quantitative component in the regulation ofHoxcgenes in the ectoderm, suggesting that these two enhancers may have evolved along with mammals to provide the level of HOXC proteins necessary for the full development of hairs and nails.Significance StatementIn this study, we report a unique and necessary function for theHoxCgene cluster in the development of some ectodermal organs, as illustrated both by the hair and nail phenotype displayed by mice lacking theHoxc13function and by the congenital anonychia (absence of nails) in fullHoxCcluster mutants. We show thatHoxcgenes are activated in a colinear manner in the embryonic limb ectoderm and are subsequently transcribed in developing nails and hairs. We identify two mammalian-specific enhancers located upstream of theHoxCcluster with and exclusive ectodermal specificity. Individual or combined enhancer deletions suggest that they act in combination to raise the transcription level of severalHoxcgenes during hairs and nails development.
A feed-forward loop between SorLA and HER3 determines heregulin response and neratinib resistance
Authors: Al-Akhrass Hussein , Conway James R.W. , Aavild Poulsen Annemarie Svane , Paatero Ilkka , Kaivola Jasmin , Padzik Artur , Andersen Olav M. , Ivaska Johanna 
Published: June 2020

Current evidence indicates that resistance to HER2-targeted therapies is frequently associated with HER3 and active signalingviaHER2-HER3 dimers, particularly in the context of breast cancer. Thus, understanding the response to HER2-HER3 signaling and the regulation of the dimerper seremains essential to decipher therapy relapse mechanisms. Here, we demonstrate that signaling by HER3 growth factor ligands, heregulins, support the transcription of a type-1 transmembrane sorting receptor, sortilin-related receptor (SorLA;SORL1) downstream of the mitogen-activated protein kinase pathway. In addition, we demonstrate that SorLA interacts directly with HER3, forming a trimeric complex with HER2 and HER3 to attenuate lysosomal degradation of the dimer through a Rab4-dependent manner. In line with a role for SorLA in supporting the stability of the HER2 and HER3 receptors, loss of SorLA compromised heregulin-induced cell proliferation and sensitized metastatic anti-HER2 therapy-resistant breast cancer cells to neratinib in cancer spheroidsin vitroandin vivoin a zebrafish brain xenograft model. Collectively, our results demonstrate a novel feed-forward loop consisting of heregulin, HER2-HER3 and SorLA, which controls breast cancer growth and anti-HER2 therapy resistancein vitroandin vivo.SignificanceHER3 signaling, through ERK/MAPK, upregulates SorLA and SorLA controls the trafficking and stability of HER3 to support cancer proliferation and neratinib resistance.