bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elucidation of cellular targets and exploitation of the receptor‐binding domain of SARS‐CoV‐2 for vaccine and monoclonal antibody synthesis
Authors: Baig Abdul Mannan , Khaleeq Areeba , Syeda Hira 
Published: June 2020

AbstractThe pandemic caused by novel severe acute respiratory syndrome coronavirus (SARS‐CoV‐2) has resulted in over 452 822 deaths in the first 20 days of June 2020 due to the coronavirus virus disease 2019 (COVID‐19). The SARS‐CoV‐2 uses the host angiotensin‐converting enzyme 2 (ACE2) receptor to gain entry inside the human cells where it replicates by using the cell protein synthesis mechanisms. The knowledge of the tissue distribution of ACE2 in human organs is therefore important to predict the clinical course of the COVID‐19. Also important is the understanding of the viral receptor‐binding domain (RBD), a region within the spike (S) proteins, that enables the entry of the virus into the host cells to synthesize vaccine and monoclonal antibodies (mAbs). We performed an exhaustive search of human protein databases to establish the tissues that express ACE2 and performed an in‐depth analysis like sequence alignments and homology modeling of the spike protein (S) of the SARS‐CoV‐2 to identify antigenic regions in the RBD that can be exploited to synthesize vaccine and mAbs. Our results show that ACE2 is widely expressed in human organs that may explain the pulmonary, systemic, and neurological deficits seen in COVID‐19 patients. We show that though the S protein of the SARS‐CoV‐2 is a homolog of S protein of SARS‐CoV‐1, it has regions of dissimilarities in the RBD and transmembrane segments. We show peptide sequences in the RBD of SARS‐CoV‐2 that can bind to the major histocompatibility complex alleles and serve as effective epitopes for vaccine and mAbs synthesis.
A prospective study of medication management during transitions from hospital to residential care: a 10‐year follow‐up to the MedGap study
Authors: Elliott Rohan A. , Boutros Yvonne , Tran Tim , Taylor Simone E. 
Published: June 2020

AbstractBackgroundProblems with continuity of medication administration after discharge from hospitals to residential care facilities (RCFs) have been reported in Australia and internationally. The MedGap study in 2009 reported a significant decline in post‐discharge missed or delayed doses and locum doctor call‐outs at RCFs following implementation of a hospital pharmacy‐prepared interim residential care medication administration chart (IRCMAC).AimTo determine whether reductions in missed or delayed doses and locum doctor call‐outs were sustained nearly 10 years after the IRCMAC was implemented, and evaluate RCFs' use of IRCMACs and discharge medications supplied in original packaging.MethodStructured telephone interviews with nurses at 52 RCFs were conducted approximately 48‐h after discharge for randomly selected patients discharged from hospitals within a major metropolitan health service in Melbourne, Australia in 2018. Results were compared with pre‐ and post‐intervention data collected using the same method in 2009. Primary endpoints were the proportion of patients for whom the RCF used the hospital‐supplied IRCMAC and discharge medications, and the incidence of missed or significantly delayed medication doses in the first 24 h post‐discharge. The number of locum doctor call‐outs was a secondary endpoint.ResultsRCFs received IRCMACs for 71/73 (97.3%) patients and used them for 61/71 (85.9%). Hospital‐supplied medication, in original packaging, was received for 65/73 (89.0%) patients and used for 59/65 (90.8%). One or more doses were missed or significantly delayed for 2/73 (2.7%) patients and locum doctors were called for nine patients (12.3%), which was similar to the 2009 post‐intervention study (6/226, 2.7% and 25/226, 11.1%, respectively) and significantly lower than the 2009 pre‐intervention study (37/202, 18.3% and 66/202, 32.7%, respectively; P < 0.01 for both endpoints). Nearly 100% of RCF staff believed IRCMACs and hospital‐supplied medication improved continuity of care.ConclusionHospital pharmacy‐prepared IRCMACs and discharge medication in original packaging were highly used and valued by RCF staff, and associated with sustained low rates of missed and delayed doses and locum doctor call‐outs.
Prevalence and Risk of Metastatic Thyroid Cancers and Management Outcomes: A National Perspective
Authors: Al‐Qurayshi Zaid , Sullivan Christopher B. , Pagedar Nitin , Lee Grace S. , Tufano Ralph , Kandil Emad 
Published: June 2020

ObjectivesExamine the prevalence and risk of metastasis in thyroid cancers and management outcomes.Study designRetrospective analysis of the National Cancer Database, 2004–2014.MethodsThe study population included adult (≥ 18 years) patients with thyroid cancer. Analysis included multivariate logistic regression and Cox hazard ratio modeling.ResultsA total of 152,979 patients were included. Distant metastasis was reported in 1,867 (1.22%) patients. The distribution of metastatic cases based on pathology and tumor size were as follows in descending order: papillary thyroid carcinoma (PTC) 1 to 4 cm (30.53%), PTC > 4 cm (19.34%), undifferentiated (UTC) > 4 cm (14.14%), PTC < 1 cm (8.46%), follicular thyroid carcinoma (FTC) > 4 cm (7.28%), FTC 1 to 4 cm (5.52%), medullary thyroid cancer (MTC) ≤ 4 cm (3.96%), MTC > 4 cm (3.91%), UTC ≤ 4 cm (3.32%), Hürthle (HCC ) > 4 cm (2.09%), and HCC 1 to 4 cm (1.45%). Significant predictors of distant metastasis, while controlling for tumor pathology and size, included older age, male gender, non‐White minorities, presence of multiple comorbidities, minimal, gross extrathyroidal extension (ETE), lymphovascular invasion (LVI), and concomitant central and lateral lymph node metastasis (LNM) (P < .05 each). The risk of distant metastasis in the absence of nodal metastasis, ETE, and LVI was highest for FTC > 4 cm.ConclusionAlthough the risk of metastasis in well‐differentiated thyroid carcinoma (WDTC) is low, the prevalence of metastatic thyroid cancer is highest in WDTC population because it is the most common type of thyroid cancer. Certain pathological features, including minimal ETE and central LNM, are associated with a higher prevalence of metastatic disease.Level of EvidenceNA Laryngoscope, 131:237–244, 2021
Expanded carrier screening in Chinese patients seeking the help of assisted reproductive technology
Authors: Xi Yanping , Chen Guangquan , Lei Caixia , Wu Junping , Zhang Shuo , Xiao Min , Zhang Wenbi , Zhang Yueping , Sun Xiaoxi 
Published: June 2020

AbstractBackgroundExpanded carrier screening (ECS) has emerged as an effective approach to identify at‐risk couples (ARCs)—before they initiate attempts at reproduction—who possess a high probability of having a child affected by severe recessive diseases. The objective of this study was to evaluate the clinical utility of ECS in Chinese patients seeking the help of assisted reproductive technology (ART).MethodsAn ECS test, which covers 201 genes implicated in 135 recessive (autosomal or X‐linked) diseases, was routinely offered to all ART patients in a single genetics and in vitro fertilization clinic. Additional options for preimplantation or prenatal genetic diagnosis were discussed and offered to all ARCs. All ECS results were aggregated and the clinical decisions of the ARCs were surveyed.ResultsA total of 2,923 ART patients, representing 1,462 couples, were screened. Overall, 46.73% of the individuals were found to be the carriers for at least 1 of the 135 diseases. Of the tested couples, 2.26% (n = 33) were identified as ARCs. As of the completion of this study, 21 (63.6%) ARCs have decided to avert an affected pregnancy with the help of preimplantation genetic testing for monogenetic conditions. The cumulative carrier rate of the 187 autosomal recessive genes in the ECS panel for the 2,836 Han Chinese individuals without a family history was estimated to be 45.91%. The estimated at‐risk couple rate indicates that the screening for only the top 31 genes with gene carrier rates >0.5% would identify more than 94% of the ARCs identified by screening all 187 genes.ConclusionOur study demonstrates that ESC yields a significant clinical value for ART patients in China. In addition, by estimating the yields of the ECS panel, we identify genes that are appropriate for screening the Han population.
Disrupted minor intron splicing is prevalent in Mendelian disorders
Authors: Olthof Anouk M. , Rasmussen Jeffrey S. , Campeau Philippe M. , Kanadia Rahul N. 
Published: June 2020

AbstractBackgroundSplicing is crucial for proper gene expression, and is predominately executed by the major spliceosome. Conversely, 722 introns in 699 human minor intron‐containing genes (MIGs) are spliced by the minor spliceosome. Splicing of these minor introns is disrupted in diseases caused by pathogenic variants in the minor spliceosome, ultimately leading to the aberrant expression of a subset of these MIGs. However, the effect of variants in minor introns and MIGs on diseases remains unexplored.MethodsVariants in MIGs and associated clinical manifestations were identified using ClinVar. The HPO database was then used to curate the related symptoms and affected organ systems. Results: We found pathogenic variants in 211 MIGs, which commonly resulted in intellectual disability, seizures and microcephaly. This revealed a subset of MIGs whose aberrant splicing may contribute to the pathogenesis of minor spliceosome‐related diseases. Moreover, we identified 51 pathogenic variants in minor intron splice sites that reduce the splice site strength and can induce alternative splicing.ConclusionThese findings highlight that disrupted minor intron splicing has a broader impact on human diseases than previously appreciated. The hope is that this knowledge will aid in the development of therapeutic strategies that incorporate the minor intron splicing pathway.
sensaas: Shape‐based Alignment by Registration of Colored Point‐based Surfaces
Authors: Douguet Dominique , Payan Frédéric 
Published: June 2020

Abstractsensaas is a tool developed for aligning and comparing molecular shapes and sub‐shapes. Alignment is obtained by registration of 3D point‐based representations of the van der Waals surface. The method uses local properties of the shape to identify the correspondence relationships between two point clouds containing up to several thousand colored (labeled) points. Our rigid‐body superimposition method follows a two‐stage approach. An initial alignment is obtained by matching pose‐invariant local 3D descriptors, called FPFH, of the input point clouds. This stage provides a global superimposition of the molecular surfaces, without any knowledge of their initial pose in 3D space. This alignment is then refined by optimizing the matching of colored points. In our study, each point is colored according to its closest atom, which itself belongs to a user defined physico‐chemical class. Finally, sensaas provides an alignment and evaluates the molecular similarity by using Tversky coefficients. To assess the efficiency of this approach, we tested its ability to reproduce the superimposition of X‐ray structures of the benchmarking AstraZeneca (AZ) data set and, compared its results with those generated by the two shape‐alignment approaches shaep and shafts. We also illustrated submatching properties of our method with respect to few substructures and bioisosteric fragments. The code is available upon request from the authors (demo version at https://chemoinfo.ipmc.cnrs.fr/SENSAAS).
Mitochondrial Dysfunction is a Key Pathway that Links Saturated Fat Intake to the Development and Progression of NAFLD
Authors: Meex Ruth C. R. , Blaak Ellen E. 
Published: June 2020

AbstractNon‐Alcoholic fatty liver disease (NAFLD) is the most common form of liver disease and is characterized by fat accumulation in the liver. Hypercaloric diets generally increase hepatic fat accumulation, whereas hypocaloric diets decrease liver fat content. In addition, there is evidence to suggest that moderate amounts of unsaturated fatty acids seems to be protective for the development of a fatty liver, while consumption of saturated fatty acids (SFA) appears to predispose toward hepatic steatosis. Recent studies highlight a key role for mitochondrial dysfunction in the development and progression of NAFLD. It is proposed that changes in mitochondrial structure and function are key mechanisms by which SFA lead to the development and progression of NAFLD. In this review, it is described how SFA intake is associated with liver steatosis and decreases the efficiency of the respiratory transport chain. This results in the production of reactive oxygen species and damage to nearby structures, eventually leading to inflammation, apoptosis, and scarring of the liver. Furthermore, studies demonstrating that SFA intake affects the composition of mitochondrial membranes are presented, and this process accelerates the progression of NAFLD. It is likely that events are intertwined and reinforce each other, leading to a constant deterioration in health.
Area deprivation is associated with poorer overall survival in children with acute lymphoblastic leukemia
Authors: Schraw Jeremy M. , Peckham‐Gregory Erin C. , Rabin Karen R. , Scheurer Michael E. , Lupo Philip J. , Oluyomi Abiodun 
Published: June 2020

AbstractBackgroundFew studies have evaluated social determinants of outcomes disparities for children with acute lymphoblastic leukemia (ALL). We investigated the association of area deprivation index (ADI), a measure of neighborhood socioeconomic disadvantage, with overall survival (OS) among children and adolescents with ALL.ProcedureWe obtained demographic and clinical data, geocoded addresses at diagnosis, and vital status on all Texas children diagnosed with ALL from 1995 to 2011 (N = 4104). Using the US Census Bureau 2010 geography, we computed ADI scores for all census tracts in Texas and grouped the tracts into quartiles: least, third‐most, second‐most, and most disadvantaged. We mapped children to ADI quartiles based on residence at diagnosis, and estimated OS using Cox regression adjusting for sex, race/ethnicity, age, and metropolitan/nonmetropolitan residence.ResultsFive‐year OS ranged from 89% (95% confidence interval [CI] 87‐91%) for children in the least disadvantaged tracts to 79% (95% CI 76‐81%) for children in the most disadvantaged tracts (P = 4E‐7). An elevated hazard ratio (HR) for death was observed for children in the most disadvantaged tracts (HR 1.57, 95% CI 1.23‐2.00), and trends toward increased mortality were observed in the third‐most and second‐most disadvantaged tracts (HR 1.23, 95% CI 0.97‐1.57 and HR 1.27, 95% CI 0.99‐1.62, respectively). In stratified analyses, area disadvantage was more strongly associated with OS in males than females.ConclusionsNeighborhood socioeconomic disadvantage is associated with inferior OS in this analysis of over 4100 children with ALL, highlighting the substantial contributions of social‐environmental factors to childhood cancer survival. This association was stronger in males than females.
Bidirectional mass transfer‐based generation of plasma‐activated water mist with antibacterial properties
Authors: Sysolyatina Elena V. , Lavrikova Aleksandra Y. , Loleyt Roman A. , Vasilieva Elena V. , Abdulkadieva Mariam A. , Ermolaeva Svetlana A. , Sofronov Aleksey V. 
Published: June 2020

AbstractPlasma‐activated water mist (PAWM) is obtained by the ignition of plasma within an air–vapor mixture. PAWM demonstrates significant antibacterial properties, decreasing loads of foodborne pathogens by a factor of 35.5 for Listeria monocytogenes, 166 for Salmonella Typhimurium, and 266 for Escherichia coli O157:H7 within 15 s. Bacterial biofilms have a similar species‐dependant susceptibility. Biofilms of L. monocytogenes, Salmonella Typhimurium, and E. coli O157:H7 are destroyed by 44%, 77%, and 71%, respectively, after being treated for 2 min. Obtained results suggest importance of short‐lived radicals, because PAWM condensate is not bactericidal. A new model of PAW generation as a cyclic process of oxidation reactive nitrogen species by reactive oxygen species, which occurs during effective bidirectional mass transfer between heavily humid air and water mist in plasma discharge, is presented.
Effect of Heating Rate on Ignition Characteristics of Newly Prepared and Aged Aluminum Nanoparticles
Authors: Jin Xiao , Li Shengji , Yang Yihang , Yang Yanjing , Huang Xuefeng 
Published: June 2020

AbstractAluminum (Al) nanoparticles have been widely applied in propellants, but the ageing of Al nanoparticles will result in the degradation of propellant ignition performance. This paper experimentally investigates the ignition characteristics of newly prepared and aged Al nanoparticles, and improves the ignition performance of aged Al nanoparticles through elevating the heating rate. It was observed that, despite newly prepared or aged Al nanoparticles, their ignition included three stages: stage I – heating, stage II – melting, and stage III – evaporation. The temperature rise and time in stage I, melting temperature, and time in stage II and ignition temperature in stage III were separately discussed. It is found that the duration of each stage during the ignition of aged Al nanoparticles was much longer than that of newly prepared Al nanoparticles, testifying that ignition temperature of Al nanoparticles increased and ignition delay time elongated due to ageing. At elevated power density, the heating rate of Al nanoparticles increased, the heating, melting, and evaporating time shortened. The difference of ignition delay time between newly prepared and aged Al nanoparticles was significantly reduced. It means that the ignition performance can be improved through increasing the heating rate. Simultaneously, the energy conversation equation of each stage was built and discussed. It will be beneficial to deeply understand the ignition process and reveal the ignition mechanism of aged Al nanoparticles.
Unified Lagrangian‐Hamiltonian Formalism for Contact Systems
Authors: de León Manuel , Gaset Jordi , Lainz Manuel , Rivas Xavier , Román‐Roy Narciso 
Published: June 2020

AbstractWe present a unified geometric framework for describing both the Lagrangian and Hamiltonian formalisms of contact autonomous mechanical systems, which is based on the approach of the pioneering work of R. Skinner and R. Rusk. This framework permits to skip the second order differential equation problem, which is obtained as a part of the constraint algorithm (for singular or regular Lagrangians), and is especially useful to describe singular Lagrangian systems. Some examples are also discussed to illustrate the method.
Linking rapid forecast error growth to diabatic processes
Authors: Sánchez Claudio , Methven John , Gray Suzanne , Cullen Mike 
Published: June 2020

AbstractThe predictability of high‐impact weather events over the North Atlantic is controlled by synoptic‐scale systems and the mesoscale structures embedded within them. Despite forecast uncertainty being greatest at small scales at the initial time, forecast error projects strongly onto synoptic and larger scales within days. Different stages of error growth have previously been identified including: convective instability, baroclinic instability and the influence of divergent outflow on the tropopause position, and interactions between disturbances at tropopause level. Evidence is presented for "predictability barriers" (PBs) identified with events on certain validation dates during the North Atlantic Waveguide and Downstream impact Experiment (NAWDEX) where ensemble spread grows more quickly than usual, but ensemble‐mean forecast error grows even faster. An advective mechanism for diabatic influence on the development of tropopause ridges is hypothesised to be linked to the PB events. A semi‐geostrophic balance tool is used to attribute the response of the 3D ageostrophic flow to geostrophic and diabatic forcing, enabling a novel diagnostic for Diabatically Induced Ageostrophic Advection (DIAA) of potential vorticity. It is shown that predictability barriers are linked to events with strong diabatic influence on tropopause advection during the NAWDEX period. Error growth exceeds ensemble spread rate by approximately 4/3 during strong DIAA events, showing that predictive skill is considerably lower in these situations.
Treatment of chronic GvHD with mesenchymal stromal cells induces durable responses: A phase II study
Authors: Boberg Erik , Bahr Lena , Afram Gabriel , Lindström Carina , Ljungman Per , Heldring Nina , Petzelbauer Peter , Garming Legert Karin , Kadri Nadir , Le Blanc Katarina 
Published: June 2020

Abstract
Steroid-refractory chronic graft-vs-host disease (cGvHD) contributes to morbidity after allogeneic hematopoietic stem cell transplantation. Here, we report on 11 patients with severe, refractory cGvHD treated with repeated infusions of allogeneic bone marrow-derived mesenchymal stromal cells (MSC) over a 6- to 12-month period. Six patients responded to MSC treatment following National Institutes of Health response criteria, accompanied by improvement in GvHD-related symptoms and quality of life. This response was durable, with systemic immunosuppressive therapy withdrawn from two responders, and a further two free from steroids and tapering calcineurin inhibitors. All responders displayed a distinct immune phenotype characterized by higher levels of naïve T cells and B cells before treatment compared with the nonresponders, and a significantly higher fraction of CD31+ naïve CD4+ T cells. MSC treatment was associated with significant increases in naïve T cells, B cells, and Tregs 7 days after each infusion. Skin biopsies showed resolution of epidermal pathology. CXCL9 and CXCL10 showed differential responses in responder and nonresponder patients. Our data support the use of MSC infusions as treatment for steroid-refractory cGvHD with durable responses. We propose CXCL9 and CXCL10 as early biomarkers for responsiveness to MSC treatment. Our results highlight the importance of the MSC recipient immune phenotype in promoting treatment response. This trial was registered at www.ClinicalTrials.gov as #NCT01522716.
Decision‐making logics and high‐tech entrepreneurial opportunity identification: The mediating role of strategic knowledge integration
Authors: Guo Runping , Lv Xingqun , Wang Yuan , Chaudhry Peggy E. , Chaudhry Sohail S. 
Published: June 2020

AbstractIn the era of Industry 4.0 and Made in China 2025 initiatives, this research is focused on exploring how entrepreneurial decision‐making logics contribute to opportunity identification by combining effectuation theory and knowledge‐based theory under high uncertainty through strategic knowledge integration in emerging economies, such as the Chinese economy. Empirical data were collected from 196 entrepreneurs and top executives in Chinese high‐tech new ventures using an interview survey. An established mediation model's assessment approach was used to test hypotheses through multivariate linear regression analyses. The analysis results show that both effectuation and causation have positive effects on opportunity identification. Also, emergent/planned knowledge integration plays a fully mediating role in the relationship between effectuation/causation and opportunity identification. This research contributes to the literature by providing empirical evidence to explain the problem of entrepreneurial opportunity identification under high uncertainty through the lens of effectuation theory. It facilitates the development of effectuation theory and enriches the literature on strategic knowledge integration. Moreover, our findings have important managerial implications for high‐tech new ventures to effectively recognize new opportunities in the context of emerging economies.