bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of de novo mutations in the Chinese ASD cohort via whole-exome sequencing unveils brain regions implicated in autism
Authors: Yuan Bo , Wang Mengdi , Wu Xinran , Cheng Peipei , Zhang Ran , Zhang Ran , Yu Shunying , Zhang Jie , Du Yasong , Wang Xiaoqun , Qiu Zilong 
Published: July 2021

AbstractAutism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder characterized by deficits in social interactions and repetitive behaviors. Although hundreds of ASD risk genes, implicated in synaptic formation and transcriptional regulation, have been identified through human genetic studies, the East Asian ASD cohorts is still under-represented in the genome-wide genetic studies. Here we performed whole-exome sequencing on 369 ASD trios including probands and unaffected parents of Chinese origin. Using a joint-calling analytical pipeline based on GATK toolkits, we identified numerous de novo mutations including 55 high-impact variants and 165 moderate-impact variants, as well as de novo copy number variations containing known ASD-related genes. Importantly, combining with single-cell sequencing data from the developing human brain, we found that expression of genes with de novo mutations were specifically enriched in pre-, post-central gyrus (PRC, PC) and banks of superior temporal (BST) regions in the human brain. By further analyzing the brain imaging data with ASD and health controls, we found that the gray volume of the right BST in ASD patients significantly decreased comparing to health controls, suggesting the potential structural deficits associated with ASD. Finally, we found that there was decrease in the seed-based functional connectivity (FC) between BST/PC/PRC and sensory areas, insula, as well as frontal lobes in ASD patients. This work indicated that the combinatorial analysis with genome-wide screening, single-cell sequencing and brain imaging data would reveal brain regions contributing to etiology of ASD.
Association of Sociodemographics with Out-of-Pocket Expenditure and Underinsurance in Skin Cancer Survivors
Authors: Karim Mohammad A. , Ohsfeldt Robert L. , Khodakarami Nima , Kum Hye-Chung 
Published: July 2021

ABSTRACTBackgroundThe sociodemographic predictors of either out-of-pocket expenditure (OOP) or underinsurance among skin cancer survivors is not well reported in the literature. In this study we estimated all-cause healthcare related OOP expenditure and probability of underinsurance among insured skin cancer survivors and identified the sociodemographic predictors of these measures.Data and MethodWe pooled Medical Expenditure Panel Survey (MEPS) data from 2011 to 2015 and identified skin cancer using Clinical Classifications Software (CCS) code. Only adult (≥18 years) skin cancer survivors with full year insurance coverage were included in our study (n = 1825). We used a generalized linear model (GLM) with log link and gamma distribution to estimate OOP and a logit model to estimate the probability of underinsurance. We estimated the Average Marginal Effect (AME) to quantify the variations and their statistical significance between reference level and other levels of each predictor. Our analyses accounted for the complex survey design of MEPS.ResultsThe average all-cause OOP was $1766 per person per year for a skin cancer survivor. Among all skin cancer survivors, females, those aged 60-64 years, with some college education or a degree, with income ≥400% of federal poverty level (FPL) and with non-managed-care private insurance incurred significantly higher OOP expenditure compared to their respective counterparts. In terms of underinsurance, females and those aged 60-64 years had higher probability, whereas, survivors with non-white race/ethnicity and income 200% of FPL or higher had lower probability of being underinsured compared to their respective counterparts.ConclusionOur study demonstrates that OOP expenditure and underinsurance varies significantly by sociodemographic factors among skin cancer survivors.
COVID-19 mortality across selected states in India: the role of age structure
Authors: Azarudeen Mohamed Jainul , Aroskar Khyati , Kurup Karishma Krishna , Dikid Tanzin , Chauhan Himanshu , Jain S.K. , Singh S.K. 
Published: July 2021

AbstractBackgroundMortality rates provide an opportunity to identify and act on the health system intervention for preventing deaths. Hence, it is essential to appreciate the influence of age structure while reporting mortality for a better summary of the magnitude of the epidemic.ObjectivesWe described and compared the pattern of COVID-19 mortality standardized by age between selected states and India from January to November 2020.MethodsWe initially estimated the Indian population for 2020 using the decadal growth rate from the previous census (2011). This was followed by estimations of crude and age-adjusted mortality rate per million for India and the selected states. We used this information to perform indirect standardization and derive the age-standardized mortality rates for the states for comparison. In addition, we derived a ratio for age-standardized mortality to compare across age groups within the state. We extracted information regarding COVID-19 deaths from the Integrated Disease Surveillance Programme special surveillance portal up to November 16, 2020.ResultsThe crude mortality rate of India stands at 88.9 per million population(118,883/1,337,328,910). Age-adjusted mortality rate (per million) was highest for Delhi (300.5) and lowest for Kerala (35.9).The age-standardized mortality rate (per million) for India is (<15 years=1.6, 15–29 years=6.3, 30–44 years=35.9, 45– 59 years=198.8, 60–74 years=571.2, ≥75 years=931.6). The ratios for age-standardized mortality increase proportionately from 45-59 years age group across all the states.ConclusionThere is high COVID-19 mortality not only among the elderly ages, but we also identified heavy impact of COVID-19 on the working population. Therefore, we recommend further evaluation of age-adjusted mortality for all States and inclusion of variables like gender, socio-economic status for standardization while identifying at-risk populations and implementing priority public health actions.
Humoral and cellular responses after a third dose of BNT162b2 vaccine in patients treated for lymphoid malignancies
Authors: Re Daniel , Seitz-Polski Barbara , Carles Michel , Brglez Vesna , Graça Daisy , Benzaken Sylvia , Liguori Stéphane , Zahreddine Khaled , Delforge Margaux , Verrière Benjamin , Chamorey Emmanuel , Jérôme Barrière 
Published: July 2021

AbstractBACKGROUNDImmunocompromised patients such as patients with hematological malignancies have impaired immune response to two doses of BNT162b2 (Pfizer / BioNtech) vaccine against SARS-CoV-2. Evaluation of a repeated immune stimulation with a third vaccine dose is needed.METHODSa vaccine monitoring observatory was conducted in outpatients who were treated for lymphoid malignancies (LM) to monitor both immune and cellular response measured the day of administration of the dose 3 of the mRNA vaccine BNT162b2 and again three to four weeks. Elecsys ® Anti-SARS-CoV-2 immunoassay was used to asses to the level of SARS-CoV-2 anti-Spike (S) antibodies (Abs) titer and SARS-CoV-2-specific T-cell responses were assessed by a whole blood Interferon-Gamma Release Immuno Assay (IGRA) (QuantiFERON Human IFN-gamma SARS-CoV-2, Qiagen®).RESULTSAmong the 43 assessable patients (suffering from chronic lymphocytic leukemia (CLL) (n=15), indolent and aggressive B cell non-Hodgkin lymphoma (NHL) (n=14), and multiple myeloma (MM) (n=16)), 18 (41,8%) had no anti-S Abs before the dose 3 of BNT162b2 vaccine (n=9 CLL, n=8 NHL, n=1 MM), and they all 18 remained negative after the dose 3. Amongst the 25 patients with positive anti-S titers before dose 3, all patients remained positive and 23 patients increased their anti-S titer after dose 3. Patients with CLL and/or with previous anti-CD20 therapy treated within 12 months of administration of dose 3 had no significant increase of the humoral response. Among 22 available patients, dose 3 of BNT162b2 vaccine significantly increased the median IFN-gamma secretion. On eight (36.4%) patients who were double-negative for both immune and cellular response, five (22.7%) patients remained double-negative after dose 3.CONCLUSIONSDose 3 of BNT162b2 vaccine stimulated humoral immune response among patients with LM, in particular patients with MM (who had higher anti-S baseline titer after dose 2) and those with no anti-CD20 treatment history within a year. T-cell response was increased among patients in particular with no active chemotherapy regimen. Our data support the use of an early third vaccine dose among immunocompromised patients followed for LM though some of them will still have vaccine failure.
Clinical and Virological Response to a Neutralizing Monoclonal Antibody for Hospitalized Patients with COVID-19
Authors:   ACTIV-3/TICO Bamlanivimab Study Group, Lundgren Jens D. , Grund Birgit , Barkauskas Christina E. , Holland Thomas L. , Gottlieb Robert L. , Sandkovsky Uriel , Brown Samuel M. , Knowlton Kirk U. , Self Wesley H. , Files D. Clark , Jain Mamta K. , Benfield Thomas , Bowdish Michael E. , Leshnower Bradley G. , Baker Jason V. , Jensen Jens-Ulrik , Gardner Edward M. , Ginde Adit A. , Harris Estelle S. , Johansen Isik S. , Markowitz Norman , Matthay Michael A. , Østergaard Lars , Chang Christina C. , Goodman Anna , Chang Weizhong , Dewar Robin L. , Gerry Norman P. , Higgs Elizabeth S. , Highbarger Helene , Murray Daniel D. , Murray Thomas A. , Natarajan Ven , Paredes Roger , Parmar Mahesh K.B. , Phillips Andrew N. , Reilly Cavan , Rupert Adam W. , Sharma Shweta , Shaw-Saliba Kathryn , Sherman Brad T. , Teitelbaum Marc , Wentworth Deborah , Cao Huyen , Klekotka Paul , Babiker Abdel G. , Davey Victoria J. , Gelijns Annetine C. , Kan Virginia L. , Polizzotto Mark N. , Thompson B. Taylor , Lane H. Clifford , Neaton James D. 
Published: July 2021

ABSTRACTBACKGROUNDBamlanivimab, a neutralizing monoclonal antibody given in combination with remdesivir, did not improve outcomes among hospitalized COVID-19 patients based on an early futility assessment. In this final study report, we evaluate an a priori hypothesis that greater benefit of bamlanivimab would be identified in those without detectable endogenous neutralizing antibody levels at study entry, especially if viral levels were high.METHODSHospitalized COVID-19 patients were randomized to receive bamlanivimab (7000mg) or placebo and followed for 90 days for sustained recovery (home for 14 consecutive days); recovery rate ratios (RRRs) are cited.RESULTSAmong 314 participants (163 on bamlanivimab and 151 on placebo), the median time to sustained recovery was 19 days and RRR=0.99 (95% CI: 0.79-1.22; p=0.89). At entry, 50% evidenced production of anti-spike neutralizing antibodies; 50% had SARS-CoV-2 nucleocapsid plasma antigen levels ≥ 1,000 ng/L. Among those without and with antibodies at study entry, the RRRs were 1.24 (95% CI: 0.90-1.70) and 0.74 (95% CI: 0.54-1.00) (p=0.02 for interaction). The RRRs were elevated for those with plasma antigen or nasal viral RNA levels above versus below median at entry, and was greatest for those without antibodies and with elevated antigen or viral RNA levels: 1.48 (95% CI: 0.99-2.23), 1.94 (1.25-3.00), respectively (p<0.05 for all interactions). Hazard ratios for safety outcomes also differed by serostatus at entry.CONCLUSIONSSustained recovery after administration of bamlanivimab versus placebo differed by presence of neutralizing antibodies at study entry, especially if participants had markers of elevated viral replication.ClinicalTrials.gov number, NCT04501978.
Antibody responses to BNT162b2 vaccination in Japan: Monitoring vaccine efficacy by measuring IgG antibodies against the receptor binding domain of SARS-CoV-2
Authors: Fujigaki Hidetsugu , Yamamoto Yasuko , Koseki Takenao , Banno Sumi , Ando Tatsuya , Ito Hiroyasu , Fujita Takashi , Naruse Hiroyuki , Hata Tadayoshi , Moriyama Saya , Takahashi Yoshimasa , Suzuki Tadaki , Murakami Takahiro , Yoshida Yukihiro , Yagura Yo , Oyamada Takayoshi , Takemura Masao , Kondo Masashi , Iwata Mitsunaga , Saito Kuniaki 
Published: July 2021

AbstractBACKGROUNDTo fight severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), mass vaccination has begun in many countries. To investigate the usefulness of a serological assay to predict vaccine efficacy, we analyzed the levels of IgG, IgM, and IgA against the receptor binding domain (RBD) of SARS-CoV-2 in the sera from BNT162b2 vaccinated individuals in Japan.METHODSThis study included 219 individuals who received two doses of BNT162b2. The levels of IgG, IgM, and IgA against RBD were measured by enzyme-linked immunosorbent assay before and after the first and second vaccination, respectively. The relationship between antibody levels and several factors including age, gender, and hypertension were analyzed. Virus-neutralizing activity in sera was measured to determine the correlation with the levels of antibodies. A chemiluminescent enzyme immunoassay (CLEIA) method to measure IgG against RBD was developed and validated for the clinical setting.RESULTSThe levels of all antibody isotypes were increased after vaccination. Among them, RBD-IgG was dramatically increased after the second vaccination. The IgG levels in females were significantly higher than in males. There was a negative correlation between age and IgG levels in males. The IgG levels significantly correlated with the neutralizing activity. The CLEIA assay measuring IgG against RBD showed a reliable performance and a high correlation with neutralizing activity.CONCLUSIONSMonitoring of IgG against RBD is a powerful tool to predict the efficacy of SARS-CoV-2 vaccination and provides useful information in considering a personalized vaccination strategy for COVID-19.
Fairness in Cardiac Magnetic Resonance Imaging: Assessing Sex and Racial Bias in Deep Learning-based Segmentation
Authors: Puyol-Antón Esther , Ruijsink Bram , Harana Jorge Mariscal , Piechnik Stefan K. , Neubauer Stefan , Petersen Steffen E. , Razavi Reza , Chowienczyk Phil , King Andrew P 
Published: July 2021

AbstractBackgroundArtificial intelligence (AI) techniques have been proposed for automation of cine CMR segmentation for functional quantification. However, in other applications AI models have been shown to have potential for sex and/or racial bias.ObjectivesTo perform the first analysis of sex/racial bias in AI-based cine CMR segmentation using a large-scale database.MethodsA state-of-the-art deep learning (DL) model was used for automatic segmentation of both ventricles and the myocardium from cine short-axis CMR. The dataset consisted of end-diastole and end-systole short-axis cine CMR images of 5,903 subjects from the UK Biobank database (61.5±7.1 years, 52% male, 81% white). To assess sex and racial bias, we compared Dice scores and errors in measurements of biventricular volumes and function between patients grouped by race and sex. To investigate whether segmentation bias could be explained by potential confounders, a multivariate linear regression and ANCOVA were performed.ResultsWe found statistically significant differences in Dice scores (white ∼94% vs minority ethnic groups 86-89%) as well as in absolute/relative errors in volumetric and functional measures, showing that the AI model was biased against minority racial groups, even after correction for possible confounders.ConclusionsWe have shown that racial bias can exist in DL-based cine CMR segmentation models. We believe that this bias is due to the imbalanced nature of the training data (combined with physiological differences). This is supported by the results which show racial bias but not sex bias when trained using the UK Biobank database, which is sex-balanced but not race-balanced.Condensed AbstractAI algorithms have the potential to reflect or exacerbate racial/sex disparities in healthcare. We aimed to determine the impact of sex and race on the performance of an AI segmentation model for automatic CMR quantification in a cohort of 5,903 subjects from the UK Biobank database, which is sex-balanced but not race-balanced. We tested the model’s bias in performance using Dice scores and absolute/relative errors in measurements of biventricular volumes and function. Our study demonstrates that the model had a racial bias but no sex bias, and that subject characteristics and co-morbidities could not explain this bias.
Transcriptional and Post-transcriptional Regulation of Ethylene Biosynthesis by Salicyclic Acid in Kiwifruit
Authors: Wang Jian , Liu Xiao-fen , Wang Wen-qiu , Zhang Hui-qin , Yin Xue-ren 
Published: July 2021

ABSTRACTLevels of ethylene, implicated in a diverse array of plants for inducing fruit ripening, is influenced by genetic and environmental factors, such as the other plant hormones. Among these, salicylic acid (SA) has been demonstrated to inhibit ethylene biosynthesis in fruit, yet the underlying regulatory mechanisms remains elusive. Here, we showed that treatment with exogenous ASA (acetylsalicylic acid) dramatically reduced ethylene production, as well as activities of ACC synthase (ACS) and ACC oxidase (ACO), in kiwifruit tissues. Comparative transcriptome analysis indicated the differential expression of ethylene biosynthetic genes (AdACS1/2 and AdACO5). A screen of transcription factors indicated that AdERF105L and AdWRKY29 were ASA-responsive regulators of AdACS1/2 and AdACO5, respectively. In addition to these genes, AdACS3 and AdACO3 were abundantly expressed in both ASA-treated and control tissues. AdACS3 protein was phosphorylated and stabilized by AdMPK16, a mitogen-activated protein kinase; while AdACO3 activity was enhanced by AdAP, an aspartic peptidase. Exogenous ASA down-regulated AdMPK16 and AdAP, thereby influencing ethylene biosynthesis at a post-transcriptional level. These findings propose a multidimensional system for SA-inhibition on ethylene biosynthesis, inducing differential expression of some ethylene biosynthesis genes, as well as differential effects on protein activity on other targets.SummaryInvolvement of transcription factors, protein kinase and aspartic peptidase in synergistically regulating salicylic acid-induced ethylene decrease in kiwifruit flesh
IT ambidexterity driven patient agility and hospital patient service performance: a variance approach
Authors: van de Wetering Rogier 
Published: July 2021

AbstractHospitals are currently exploring digital options to transform their clinical procedures and their overall engagement with patients. This paper investigates how hospital departments can leverage the ability of firms to simultaneously explore new IT resources and practices (IT exploration) as well as exploit their current IT resources and practices (IT exploitation), i.e., IT ambidexterity, to adequately sense and respond to patients’ needs and demands, i.e., patient agility. This study embraces the dynamic capability view and develops a research model, and tests it accordingly using cross-sectional data from 90 clinical hospital departments from the Netherlands through an online survey. The model’s hypothesized relationships are tested using Partial Least Squares (PLS) structural equation modeling (SEM). The outcomes demonstrate the significance of IT ambidexterity in developing patient agility, positively influencing patient service performance. The study outcomes support the theorized model can the outcomes shed light on how to transform clinical practice and drive patient agility.
Performance of a machine learning model in recognition of normal tissue from histological sections
Authors: Sanyal Parikshit , Paul Sayak , Das Avinash 
Published: July 2021

AbstractIntroductionMachine learning and artificial intelligence (AI) models have been applied in histopathology to solve specific problems like detection of metastasis in lymph nodes and immunohistochemical scoring. We have aimed to develop a machine learning model which can be trained in histopathology from the basics, i.e. identification of normal tissue. We have tried to replicate the process through which a human pathologist learns recognition of normal tissue from histological sections, and evaluate the performance of a machine learning model at this task.Materials and methodsA total of 658 histologic images were anonymised, microphotographed at 10x magnification, under the same condition of illumination, with a Magnus DC5 integrated microphotography system. The images were split into two subsets, training (386) and validation (272 images). The images belonged to seven classes of tissue: brain, intestine, kidney, liver, lungs, muscle and skin. Archived material of the hospital were used for the study. A machine learning model using convolutional neural network (CNN) was developed on the Keras platform, using the convolution layers of a pretrained VGG16 model. The model was trained with the training set of images over 10 epochs. After training, performance of the model was assessed on the validation set.ResultsThe model achieved 88.24% accuracy in classifying the images of the validation set. The most frequent errors were met in recognising images of kidney (14 errors, 33.33%). The commonest error was wrongly classifying kidney tissue as liver (07 errors). Analysis of the deeper layers of the neural network revealed specific patterns in images which were wrongly classified.ConclusionThe results of the present study indicates that a convolutional neural network might be trained in histology similar to a trainee pathologist. The study represents the first step towards developing a machine learning model as a generalised histopathological image classifier.
Degradation of Red Blood Cell Deformability during Cold Storage in Blood Bags
Authors: Islamzada Emel , Matthews Kerryn , Lamoureux Erik , Duffy Simon P. , Scott Mark D. , Ma Hongshen 
Published: July 2021

ABSTRACTRed blood cells (RBCs) stored in blood bags develop a storage lesion that include structural, metabolic, and morphologic transformations resulting in a progressive loss of RBC deformability. The speed of RBC deformability loss is donor-dependent, which if properly characterized, could be used as a biomarker to select high-quality RBC units for sensitive recipients or to provide customized storage timelines depending on the donor. We used the microfluidic ratchet device to measure the deformability of red blood cells stored in blood bags every 14 days over a span of 56 days. We observed that storage in blood bags generally prevented RBC deformability loss over the current standard 42-day storage window. However, between 42 and 56 days, the deformability loss profile varied dramatically between donors. In particular, we observed accelerated RBC deformability loss for a majority of male donors, but for none of the female donors. Together, our results suggest that RBC deformability loss could be used to screen for donors who can provide stable RBCs for sensitive transfusion recipients or to identify donors capable of providing RBCs that could be stored for longer than the current 42-day expiration window.
Displacement statistics of unhindered single molecules show no enhanced diffusion in enzymatic reactions
Authors: Choi Alexander A. , Park Ha H. , Chen Kun , Yan Rui , Li Wan , Xu Ke 
Published: July 2021

ABSTRACTRecent studies have sparked heated debate over whether catalytical reactions would enhance the diffusion coefficients D of enzymes. Through high statistics of the transient (600 μs) displacements of unhindered single molecules freely diffusing in common buffers, we here quantify D for four highly contested enzymes under catalytic turnovers. We thus formulate how precisions of better than ±1% may be achieved for D at the 95% confidence level, and show no changes in diffusivity for catalase, urease, aldolase, and alkaline phosphatase under the application of wide concentration ranges of substrates. Our single-molecule approach thus overcomes potential limitations and artifacts underscored by recent studies to show no enhanced diffusion in enzymatic reactions.Table of Contents artwork