medRxiv (Cold Spring Harbor Laboratory)最新文献

{"title":"Multiomic analysis reveals cellular and epigenetic plasticity in intestinal pouches of ulcerative colitis patients","authors":"Yu Zhao, Ran Zhou, Bingqing Xie, Cambrian Y Liu, Martin Kalski, Candace M Cham, Jason Koval, Christopher R Weber, David T Rubin, Mitch Sogin, Sean Crosson, Jun Huang, Aretha Fiebig, Sushila Dalal, Eugene B Chang, Anindita Basu, Sebastian Pott","doi":"10.1101/2023.11.11.23298309","DOIUrl":"https://doi.org/10.1101/2023.11.11.23298309","url":null,"abstract":"Background & Aims: Total proctocolectomy with ileal pouch anal anastomosis (IPAA) is the standard of care for patients with severe treatment resistant ulcerative colitis (UC). Despite improvements in patient outcomes, about 50% of patients will develop inflammation of the pouch within 1-2 years following surgery. Establishment of UC pouches is associated with profound histological changes of the mucosa. A detailed characterization of these changes on a cellular and molecular level is crucial for an improved understanding of pouch physiology and diseases management. Methods: We generated cell-type-resolved transcriptional and epigenetic atlases of UC pouches using scRNA-seq and scATAC-seq data from paired biopsy samples from the ileal pouch and ileal segment above the pouch (pre-pouch) of UC-IPAA patients (n=6, female=2) without symptoms. We also collected data from paired biopsies of the terminal ileum (TI) and ascending colon (AC) from healthy controls (n=6, female=3). Results: We identified novel populations of colon-like absorptive and secretory epithelial cells, constituting a significant proportion of the epithelial cell fraction in the pouch but not in matched pre-pouch samples. Pouch-specific enterocytes expressed colon-specific genes, including CEACAM5, CA2. However, in contrast to normal colonic epithelium, these cells also expressed a range of inflammatory and secretory genes, similar to previously detected gene expression signatures in IBD patients. Comparison to longitudinal bulk RNA-seq data from UC pouches demonstrated that colon-like epithelial cells are present early after pouch functionalization and independently of subsequent pouchitis. Finally, single cell chromatin accessibility revealed activation colonic transcriptional regulators, including CDX1, NFIA, and EHF. Conclusion: UC pouches are characterized by partial colonic metaplasia of the epithelium. These data constitute a resource of transcriptomic and epigenetic signatures of cell populations in the pouch and provide an anchor for understanding the underlying molecular mechanisms of pouchitis.","PeriodicalId":478577,"journal":{"name":"medRxiv (Cold Spring Harbor Laboratory)","volume":"64 7","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136347998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psychometric properties of the Dutch London Measure of Unplanned Pregnancy for pregnant people and their partners","authors":"Merel Sprenger, Wieke Y. Beumer, Jenneke M. van Ditzhuijzen, Jessica C. Kiefte-de Jong","doi":"10.1101/2023.11.13.23298453","DOIUrl":"https://doi.org/10.1101/2023.11.13.23298453","url":null,"abstract":"Context. It is often unclear what constitutes an unplanned or unintended pregnancy, and pregnancy intentions may be multidimensional dynamic. The London Measure of Unplanned Pregnancy (LMUP) measures pregnancy intentions in a manner close to the actual experience. The aim of this study is to establish a Dutch version of the LMUP (LMUP-NL) and to evaluate the reliability and validity of this version for both people who were pregnant and their partners, whatever the pregnancy outcome. Methods. A psychometric evaluation of the LMUP using observational data from the BluePrInt study and the RISE UP study was conducted with 1201 people (839 people who were pregnant and 362 partners), aged between 16-55 years. The LMUP-NL was translated based using the Flemish LMUP and the UK 2020 update, resulting in a version for people who were pregnant and one for partners. Next, the acceptability, readability, reliability, construct and convergent validity were analyzed, combining Principal Component analysis, Confirmatory Factor analysis and Mokken scale analyses. Results. The LMUP-NL demonstrated to be readable and reliable (Cronbach's alpha >0.80 for both versions). Construct validity of both versions was acceptable (CFI>0.93) and Mokken scale analyses indicated a strong scale (H-coefficient:0.68). Conclusions. The LMUP-NL is reliable and valid for people who were pregnant and their partners, regardless of the pregnancy outcome. It offers researchers and policy makers an instrument suitable to measure pregnancy intention in a multidimensional manner, constituting a closer reflection of the actual experience of pregnancy intentions.","PeriodicalId":478577,"journal":{"name":"medRxiv (Cold Spring Harbor Laboratory)","volume":"48 24","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136281497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Whole-exome and Whole-genome Sequencing of 1097 Individuals with Type 1 Diabetes Reveals Novel Genes for Diabetic Kidney Disease","authors":"Jani K Haukka, Anni Antikainen, Erkka Valo, Anna Syreeni, Emma dahlstrom, Bridget Lim, Nora Franceschini, Valma Harjutsalo, Per-Henrik Groop, Niina Sandholm","doi":"10.1101/2023.11.13.23298447","DOIUrl":"https://doi.org/10.1101/2023.11.13.23298447","url":null,"abstract":"Background and hypothesis: Diabetic kidney disease (DKD) is a severe diabetic complication affecting one third of individuals with type 1 diabetes. Although several genes and common variants have been associated with DKD, much of the predicted inheritance remain unexplained. Here, we performed next-generation sequencing to assess whether low-frequency variants - single or aggregated - contribute to the missing heritability in DKD. Methods: We performed whole-exome sequencing (WES) of 498 individuals and whole-genome sequencing (WGS) of 599 individuals with type 1 diabetes. After quality control, we had next-generation sequencing data available for altogether 1064 individuals, of whom 546 had developed either severe albuminuria or end-stage kidney disease, and 528 had retained normal albumin excretion despite a long duration of type 1 diabetes. Single variants and gene aggregate tests were performed separately for WES and WGS data and combined with meta-analysis. Furthermore, we performed genome-wide aggregate analyses on genomic windows (sliding-window), promoters, and enhancers with the WGS data set. Results: In single variant meta-analysis, no variant reached genome-wide significance, but a suggestively associated THAP7 rs369250 variant ( P =1.50*10 -5 ) was replicated in the FinnGen general population GWAS data for chronic kidney disease (CKD) and DKD phenotypes. Gene-aggregate meta-analysis identified suggestive evidence ( P <4.0*10 -4 ) at four genes for DKD, of which NAT16 and LTA ( TNB-β ) replicated in FinnGen. Of the intergenic regions suggestively associated with DKD, the enhancer on chromosome 18q12.3 ( P =3.94*10 -5 ) showed interaction with the METTL4 gene; the lead variant was replicated, and predicted to alter Mafb binding. Conclusions: Our sequencing-based meta-analysis revealed multiple genes, variants and regulatory regions suggestively associated with DKD. However, as no variant or gene reached genome-wide significance, further studies are needed to validate the findings.","PeriodicalId":478577,"journal":{"name":"medRxiv (Cold Spring Harbor Laboratory)","volume":"45 16","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136282234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Binary classification of English Reddit posts self-reporting a social anxiety disorder diagnosis","authors":"Sharandeep Singh, Jatin Bedi","doi":"10.1101/2023.11.10.23298362","DOIUrl":"https://doi.org/10.1101/2023.11.10.23298362","url":null,"abstract":"This paper presents the system developed by Team ThaparUni for the Social Media Mining for Health Applications (SMM4H) 2023 Shared Task 4. The task involved binary classification of English Reddit posts, focusing on self-reporting social anxiety disorder (SAD) diagnoses. The final system employed a combination of three models: RoBERTa, ERNIE, and XLNet, and results obtained from all three models were integrated. The results, specifically in the context of mental health-related content analysis on social media platforms, show the possibility and viability of using multiple models in binary classification tasks.","PeriodicalId":478577,"journal":{"name":"medRxiv (Cold Spring Harbor Laboratory)","volume":"19 9","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136351763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prodromal symptoms of rheumatoid arthritis in a primary care database: variation by ethnicity and socioeconomic status","authors":"Alexander d'Elia, Aliaksandra Baranskaya, Shamil Haroon, Ben Hammond, Nicola J Adderley, Krishnaraja Nirantharakumar, Karim Raza","doi":"10.1101/2023.11.13.23298446","DOIUrl":"https://doi.org/10.1101/2023.11.13.23298446","url":null,"abstract":"Objectives To assess whether prodromal symptoms of rheumatoid arthritis (RA), as recorded in the Clinical Practice Research Datalink Aurum (CPRD) database of English primary care records, differ by ethnicity and socioeconomic status. Methods A cross-sectional study to determine the coding of common symptoms (≥0.1 % in the sample) in the 24 months preceding RA diagnosis in CPRD Aurum, recorded between January 1st 2004 to May 1st 2022. Eligible cases were adults with a code for RA diagnosis. For each symptom, a logistic regression was performed with the symptom as dependent variable, and ethnicity and socioeconomic status as independent variables. Results were adjusted for sex, age, BMI, and smoking status. White ethnicity and the highest socioeconomic quintile were comparators. Results In total, 70115 cases were eligible for inclusion, of which 66.4 % female. Twenty-one symptoms were coded in more than 0.1 % of cases so were included in the analysis. Patients of South Asian ethnicity had higher frequency of codes for several symptoms, with the largest difference by odds ratio being muscle cramps (OR 1.71, 1.44-2.57) and shoulder pain (1.44, 1.25-1.66). Patients of Black ethnicity had higher prevalence of several codes including unintended weight loss (2.02, 1.25-3.28) and ankle pain (1.51, 1.02-2.23). Low socioeconomic status was associated with morning stiffness (1.74, 1.08-2.80) and falls (1.37, 2.03-1.82) Conclusion There are significant differences in coded symptoms between demographic groups, which must be considered in clinical practice in diverse populations and to avoid algorithmic bias in prediction tools derived from routinely collected healthcare data.","PeriodicalId":478577,"journal":{"name":"medRxiv (Cold Spring Harbor Laboratory)","volume":"49 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136281496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of non-invasive ventilation on exacerbation frequency in COPD patients","authors":"Maximilian Zimmermann, Georgi Margalitadze, Doreen Kroppen, Wolfram Windisch, Daniel Sebastian Majorski, Melanie Berger, Sarah Bettina Stanzel, Maximilian Wollsching-Strobel","doi":"10.1101/2023.11.13.23298441","DOIUrl":"https://doi.org/10.1101/2023.11.13.23298441","url":null,"abstract":"BACKGROUND: Acute exacerbations of COPD are key events in the natural course of the patients illness, as they significantly impair the health condition, accelerate the deterioration of lung function, worsen the prognosis for the patient and account for the majority of the COPD-related healthcare costs. Particularly in patients with a pre-existing non-invasive ventilation (NIV) therapy, a reduction of exacerbation frequency is crucial, as they are at high risk for a lasting morbidity and increased mortality. METHODOLOGY: A prospective cohort study was conducted. Data from adult patients with the diagnosis COPD and existing High-Intensity NIV (HINIV) therapy from August 2021 to September 2023 was analyzed. Exacerbation history of moderate and severe exacerbations of the past 12 months and blood gases at initiation and during HINIV therapy were analyzed. RESULTS: 20 patients were included (mean age 69.2 ±9 years; 70% female). After initiation of HINIV therapy the frequency of exacerbation displayed a significant reduction from 1.5±0.9 to 0.5±0.5 per year (p<0.001). In addition, improvements in pCO2 (73.0±22.0 mmHg vs. 44.0±4.8 mmHg; p<0.001), the pH (7.33±0.1 vs. 7.42± 0; p<0.001) and HCO3- (33.0±4.9 mmol/l vs. 27.9±3.2 mmol/l; p<0.001) were successfully demonstrated. DISCUSSION: The present study demonstrates the positive effects of high-intensity NIV on exacerbation rate, measured by the number of moderate and severe exacerbations in one year. Most significant effects were observed when patients had a high number of exacerbations before the initiation of NIV therapy.","PeriodicalId":478577,"journal":{"name":"medRxiv (Cold Spring Harbor Laboratory)","volume":"46 9","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136282383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating stimulus-organism-response model and theory of planned behavior to explore athletes’ intention to receive the COVID-19 vaccine booster - A moderated mediation model","authors":"Wenpeng Zhan, Qianting Deng, Van Bac Nguyen, Tran Phan Duc Anh, Phan Danh Na, An-Shin Shia, Gordon Chih Ming Ku","doi":"10.1101/2023.11.13.23298480","DOIUrl":"https://doi.org/10.1101/2023.11.13.23298480","url":null,"abstract":"This study aims to investigate the factors influencing athletes' intention to receive the COVID-19 vaccine booster in Mainland China by integrating the stimulus-organization-response (SOR) model and theory of planned behavior (TPB) as the theoretical framework. Purposive sampling was used to select respondents from the National Games of the People's Republic of China. Hard-copy questionnaires were utilized to collect data, resulting in 981 valid responses. Descriptive analysis and partial least squares structural equation modeling were used to analyze the data. The findings reveal that athletes' subjective norm and knowledge significantly influence attitude, commitment, and perceived behavioral control. Attitude, commitment, and perceived behavioral control are verified as full mediators between subjective norm, knowledge, and intention to receive the COVID-19 vaccine booster. Knowledge to commitment is the most powerful path to predict athletes' intention to receive the COVID-19 vaccine booster. Motivation moderates the relationships between knowledge, attitude, commitment, and perceived behavioral control. The integrating model's explanatory power is 83.2%. Athletes' knowledge is crucial in shaping a positive attitude, commitment, and perceived control, enhancing their intention to get the COVID-19 vaccine booster.","PeriodicalId":478577,"journal":{"name":"medRxiv (Cold Spring Harbor Laboratory)","volume":"76 2","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136348108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A SOLUTION TO THE KERMACK AND MCKENDRICK INTEGRO-DIFFERENTIAL EQUATIONS WHICH ACCURATELY PROJECTS COVID-19 CASE DATA USING GOOGLE MOBILITY DATA AS AN INPUT","authors":"Theodore G Duclos, Thomas Reichert","doi":"10.1101/2023.11.13.23298463","DOIUrl":"https://doi.org/10.1101/2023.11.13.23298463","url":null,"abstract":"In this manuscript, we derive a closed form solution to the full Kermack and McKendrick integro-differential equations (Kermack and McKendrick 1927) which we call the KMES. We demonstrate the veracity of the KMES using the Google Residential Mobility Measure to accurately project case data from the Covid 19 pandemic and we derive many useful, but previously unknown, analytical expressions for characterizing and managing an epidemic. These include expressions for the viral load, the final size, the effective reproduction number, and the time to the peak in infections. The KMES can also be cast in the form of a step function system response to the input of new infections; and that response is the time series of total infections. Since the publication of Kermack and McKendricks seminal paper (1927), thousands of authors have utilized the Susceptible, Infected, and Recovered (SIR) approximations; expressions putatively derived from the integro-differential equations to model epidemic dynamics. Implicit in the use of the SIR approximation are the beliefs that there is no closed form solution to the integro-differential equations, and that the approximation is a special case which adequately reproduces the dynamics of the integro-differential equations mapped onto the physical world. However, the KMES demonstrates that the SIR approximations are not adequate representations of the integro-differential equations, and we therefore suggest that the KMES obsoletes the need for the SIR approximations by providing not only a new mathematical perspective, but a new understanding of epidemic dynamics.","PeriodicalId":478577,"journal":{"name":"medRxiv (Cold Spring Harbor Laboratory)","volume":"69 6","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136349751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MaSk-LMM: A Matrix Sketching Framework for Linear Mixed Models in Association Studies","authors":"Myson C Burch, Aritra Bose, Gregory Dexter, LAXMI PARIDA, Petros Drineas","doi":"10.1101/2023.11.13.23298469","DOIUrl":"https://doi.org/10.1101/2023.11.13.23298469","url":null,"abstract":"Linear mixed models (LMMs) have been widely used in genome-wide association studies (GWAS) to control for population stratification and cryptic relatedness. Unfortunately, estimating LMM parameters is computationally expensive, necessitating large-scale matrix operations to build the genetic relatedness matrix (GRM). Over the past 25 years, Randomized Linear Algebra has provided alternative approaches to such matrix operations by leveraging matrix sketching, which often results in provably accurate fast and efficient approximations. We leverage matrix sketching to develop a fast and efficient LMM method called Matrix-Sketching LMM (MaSk-LMM) by sketching the genotype matrix to reduce its dimensions and speed up computations. Our framework comes with both theoretical guarantees and a strong empirical performance compared to current state-of-the-art.","PeriodicalId":478577,"journal":{"name":"medRxiv (Cold Spring Harbor Laboratory)","volume":"68 6","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136348404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Personalizing treatment selection in Crohn's disease: a meta-analysis of individual participant data from fifteen randomized controlled trials","authors":"Vivek Ashok Rudrapatna, Vignesh Ravindranath, Douglas Victor Arneson, Arman Mosenia, Atul Janardhan Butte, Shan Wang","doi":"10.1101/2023.11.10.23291837","DOIUrl":"https://doi.org/10.1101/2023.11.10.23291837","url":null,"abstract":"BACKGROUND Crohn's disease is characterized by diverse manifestations that likely reflect differences in disease biology and treatment responsiveness across patients. Prior meta-analyses have found anti-TNF drugs to be more efficacious than others based on their cohort-averaged effects. We performed a subgroup analysis to determine if it is possible to achieve even more efficacious outcomes by individualizing treatment selection. METHODS We obtained participant-level data from 15 trials of FDA-approved treatments (N=5703). We used sequential regression and simulation to model week six disease activity as a function of drug class, demographics, and disease-related features. We used hypothesis testing to define subgroups based on rank-ordered preferences for drug classes. We queried data from University of California Health (UCH) to estimate the impacts these models could have on clinical practice. We computed the sample size needed to prospectively test a key prediction of our model. Lastly, we prototyped a treatment recommendation tool that uses patient features as inputs. FINDINGS 55% of all participants (N=3142) did not show superior efficacy with any one drug class (anti-TNF, anti-IL-12/23, anti-integrin). We classified the remainder into 6 treatment subgroups, two of which showed greatest efficacy with anti-TNFs (36%, N=2064). We also identified a subgroup of women over 50 with superior responses to anti-IL-12/23s. Although they represented only 2% of the trial-based cohort, 25% of Crohn's patients at UCH are women over 50 (N=5,647). During the timeframe when all drug classes were FDA-approved, 75% of biologic-exposed women over 50 did not receive an anti-IL12/23 first-line. We calculate that a trial with 250 patients per arm will have 97% power to show anti-IL-12/23s as being superior to anti-TNFs in these patients. INTERPRETATION Personalizing treatment selection with the aid of decision support tools can improve outcomes in Crohn's disease. FUNDING: UCSF, USF","PeriodicalId":478577,"journal":{"name":"medRxiv (Cold Spring Harbor Laboratory)","volume":"13 2","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135037205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}