bluuebunny/crossref_metadata_2025_split huggingface dataset:
Process Improvement of Adeno-Associated Virus Production
Authors: Guan Jia-Shiung , Chen Kai , Si Yingnan , Kim Taehyun , Zhou Zhuoxin , Kim Seulhee , Zhou Lufang , Liu Xiaoguang 
Published: January 2022

Adeno-associated viruses (AAVs) have been well characterized and used to deliver therapeutic genes for diseases treatment in clinics and basic research. This study used the triple transient transfection of AAV-DJ/8 as a model expression system to develop and optimize the laboratory production of AAV for research and pre-clinical applications. Specifically, various production parameters, including host cell, transfection reagent, cell density, ratio of plasmid DNA and cells, gene size, and production mode, were tested to determine the optimal process. Our results showed that the adherent production using HEK 293AAV with calcium transfection generated the highest volumetric productivity of 7.86 × 109 gc/ml. The optimal suspensive production using HEK 293F had best AAV productivity of 5.78 × 109 gc/ml in serum-free medium under transfection conditions of transfection density of 0.4 × 106 cells/ml, plasmid DNA:cells ratio of 1.6 µg:106 cells and synthesized cationic liposomes as transfection reagent. The similar AAV productivity was confirmed at scales of 30–450 ml in shaker and/or spinner flasks. The in vitro transfection and in vivo infection efficiency of the harvested AAV-DJ/8 carrying luciferase reporter gene was confirmed using cell line and xenograft mouse model, respectively. The minimal or low purification recovery rate of AAV-DJ/8 in ion-exchange chromatography column and affinity column was observed in this study. In summary, we developed and optimized a scalable suspensive production of AAV to support the large-scale preclinical animal studies in research laboratories.
Modified Taiwan Atrial Fibrillation Score for the Prediction of Incident Atrial Fibrillation
Authors: Liao Jo-Nan , Lim Su-Shen , Chen Tzeng-Ji , Tuan Ta-Chuan , Chen Shih-Ann , Chao Tze-Fan 
Published: January 2022

BackgroundWe have proposed the Taiwan AF score consisting of age, male sex, hypertension, heart failure, coronary artery disease, end-stage renal disease, and alcoholism to predict incident atrial fibrillation (AF) in Asian population. We hypothesized that the modified Taiwan AF score (mTaiwan AF score) excluding alcoholism remained useful for predicting new onset AF.MethodsA total of 7,220,654 subjects aged ≥ 40 years without a past history of cardiac arrhythmia were identified from a national cohort, and 438,930 incident AF occurred during a 16-year follow-up with an incidence of 0.42 per 100 person-years. The mTaiwan AF score ranging between −2 and 14 and its predictive accuracy of incident AF was analyzed.ResultsThe areas under the receiver operating characteristic curve (AUCs) of the mTaiwan AF scores in predicting AF are 0.861 for 1-year follow-up, 0.829 for 5-year follow-up, 0.795 for 10-year follow-up, and 0.751 for 16-year follow-up. The risk of incident AF increased from 0.05%/year for patients with a score of −2 to 6.98%/year for those having a score of 14. Patients were classified into three groups based on the tertile values of the mTaiwan AF scores—group 1 (score −2-3), group 2 (score 4-9) and group 3 (score 10-14). The annual risks of incident AF were 0.20, 1.33, and 3.36% for group 1, 2, and 3, respectively. Compared to patients in group 1, the hazard ratios of incident AF were 5.79 [95% confidence interval (CI) 3.75-7.75] for group 2 and 8.93 (95% CI 6.47-10.80) for group 3.ConclusionsWe demonstrated that the mTaiwan AF score based on age and clinical comorbidities could be used to predict incident AF in Asian population.
Blood Group O Protect End-Stage Renal Disease Patients With Dialysis From Coronary Artery Disease
Authors: Ye Zixiang , Wu Yaxin , Tu Yimin , Chen Mulei , Gao Yanxiang , Shi Linying , Li Peizhao , Xie Enmin , Guo Ziyu , Li Qing , Yu Xiaozhai , Li Yike , Niu Wenquan , Ren Jingyi , Zheng Jingang 
Published: January 2022

ObjectiveOur study aims to investigate the role of the ABO blood group in the development and severity of coronary artery disease (CAD) in end-stage renal disease (ESRD) patients with dialysis.MethodsA total of 408 ESRD patients with dialysis between January 2010 and December 2020 were enrolled including 204 patients diagnosed with CAD undergoing coronary angiography for the first time, and baseline characteristics as well as Gensini score (GS) were collected. Logistic regression analysis and linear regression analysis were performed to evaluate the relation of ABO blood types to the risk and severity of CAD, respectively.ResultsBlood group O frequency was significantly low in dialysis ESRD patients with CAD (25 vs. 38.24%) compared with the non-CAD patients and multivariable logistic regression showed blood group O was negatively associated with the risk of CAD [adjusted odds ratio (OR) = 0.33, 95% CI = 0.19–0.60, p &lt; 0.001] as well as the GS tertiles (adjusted OR = 0.23, 95% CI = 0.11–0.49, p &lt; 0.001) compared with A blood group. Blood group A, B, and AB were positively associated with the high Gensini tertile compared with O blood group (adjusted OR = 4.26, 95% CI = 2.03–8.93, p &lt; 0.001; adjusted OR = 2.39, 95% CI = 1.11–5.13, p &lt; 0.05; adjusted OR = 4.33, 95% CI = 1.40–13.35, P &lt; 0.05). Similarly, multivariable linear regression results revealed O blood type was negatively associated with the GS (β = −26.129, 95% CI = −40.094 to −12.164, p &lt; 0.001).ConclusionThis case-control study demonstrated that blood group O was a potential independent protective factor for the risk and severity of CAD in ESRD patients with dialysis.
Outcomes of Different Ablation Approaches for Para-Hisian Accessory Pathway and Ablation Safety at Each Site
Authors: Yang Jian-du , Sun Qi , Guo Xiao-gang , Zhou Gong-bu , Liu Xu , Wei Hui-qiang , Xie Hai-yang , Ma Jian 
Published: January 2022

BackgroundThis study describes the electrophysiologic characteristics of the para-hisian accessory pathway (AP), the outcome of different ablation approaches, and ablation safety at different sites.MethodA total of 120 patients diagnosed as para-hisian AP were included in this study. The electrophysiologic characteristics and outcomes at different ablation sites were analyzed.ResultsIn total, 107 APs and 13 APs were diagnosed as right anteroseptal (RAS) and right midseptal (RMS), respectively. The significant ECG difference between RAS and RMS was lead III, which mainly manifested as positive and negative delta waves, respectively. Catheter trauma to AP was recorded in 21 of 120 (17.5%) patients. The recurrence rate of direct ablation at the “bumped” sites was higher than the conventional ablation method (37.5 vs. 14.1 %, p = 0.036). For RAS APs, there was no significant difference in the success rate between the inferior vena cava (IVC) and superior vena cava (SVC) approaches (76.6 vs. 73.3%, p = 0.63). The RAS was separated into three regions: (1) Site 1: superior part above the real “His” recorded site with far-field “His” potential; (2) Site 2 (true para-hisian): the site with near-field “His” potential; and (3) Site 3: inferior part below the biggest real “His” with far-field “His” potential. Mid-septal was defined as an area that is bounded anteriorly by His recording location and posteriorly by the roof of coronary sinus (CS) ostium. The incidence of atrioventricular (AV) conduction injury at different sites was as follows: 3 of 6 (50%) at Site 2, 4 of 13 (30.8%) at RMS, 7 of 34 (20.6%) at Site 3, and 3 of 46 (6.5%) at Site 1. Even if ablation was performed at the atrial side of the para-hisian region, the right bundle branch block (RBBB) was caused in 6 patients (5%).ConclusionAblation via IVC or SVC was comparative for para-hisian APs, but not for the noncoronary cusp (NCC) approach. The AV conduction injury risk ranks as follows: Site 2 &gt; RMS &gt; Site 3 &gt; Site 1. RBBB could be caused while ablating at the atrial side, which could further demonstrate the His bundle longitudinal dissociation theory.
Multimorbidity and Polypharmacy in Chinese Emergency Department Patients With Atrial Fibrillation and Impacts on Clinical Outcomes
Authors: Wang Juan , Yang Yan-min , Zhu Jun , Zhang Han , Shao Xing-hui 
Published: January 2022

Background and ObjectsFew studies focus on multimorbidity and polypharmacy in Chinese atrial fibrillation (AF) patients. We examined the impact of multimorbidity, polypharmacy, and treatment strategies on outcomes in Chinese emergency department (ED)AF patients. We also assessed factors associated with vitamin K antagonist (VKA) non-use in AF patients with multimorbidity or polypharmacy.Methods2015 AF patients who presented to emergency department (ED) were enrolled from Nov 2008 to Oct 2011, mean follow-up of 12-months. Cox regressions were performed to identify the impact of multimorbidity and polypharmacy on clinical outcomes.ResultsSix hundred and sixty-five patients in low morbidity group (≤1 comorbidity), 608 patients in moderate morbidity group (2 comorbidities), 742 patients in high morbidity group (≥3 comorbidities). Five hundred and seventy patients (28.3%) had polypharmacy (≥5 medications). High and moderate morbidity groups were significantly associated with a higher risk of all-cause death (HR 2.083, 95%CI 1.482–2.929; HR 1.713, 95%CI 1.198–2.449), CV death (HR 2.457, 95%CI 1.526–3.954; HR 1.974, 95%CI 1.206–3.232) and major bleeding (HR 4.126, 95%CI 1.022–16.664; HR 6.142, 95%CI 1.6789–22.369) compared with low morbidity group. In VKA subgroup, only high morbidity group was associated with a higher risk of all-cause death (HR 2.521, 95%CI 1.482–2.929), but not significantly in other events. For polypharmacy category, there were no significant statistics among these endpoints. Coronary artery disease (CAD), hypertension, chronic obstructive pulmonary disease, and antiplatelet therapy were independent predictors for VKA non-use in whole cohort, and patients with multimorbidity. CAD and antiplatelet therapy were independent predictors for VKA non-use in patients with polypharmacy.ConclusionMultimorbidity was associated with worse outcomes in Chinese ED AF patients. Polypharmacy showed no significant statistics among these outcomes. CAD and antiplatelet therapy were independent risk factors of VKA non-use in Chinese ED AF patients with multimorbidity or polypharmacy.
Association of Central Obesity With All Cause and Cause-Specific Mortality in US Adults: A Prospective Cohort Study
Authors: Huai Pengcheng , Liu Jian , Ye Xing , Li Wen-Qing 
Published: January 2022

BackgroundPrevious data on the association between central obesity and mortality are controversial. The aim of this study was to determine the associations between central obesity, as measured by the waist-to-height ratio (WtHR) and waist circumference (WC), with all cause and cause-specific mortality in U.S. adults.MethodsThe study subjects comprised a nationally representative sample of 33,569 adults &gt;20 years of age who were recruited in the National Health and Nutrition Examination Survey between 1999 and 2014. Anthropometric data, including weight, height, and WC, were measured at each of the eight waves using consistent methodology. Death and underlying causes of death were ascertained through 31 December 2015. The association between central obesity and mortality were determined using weighted Cox proportional hazards regression models.ResultsA total of 4013 deaths occurred during a median follow-up of 7.33 years (263,029 person-years). Compared with the subjects in WtHR tertile 1, the subjects in tertiles 2 and 3 were at a higher risk of mortality from all-cause (tertile 2-hazard ratio [HR]: 1.29; 95% confidence interval [CI]: 1.13–1.47; tertile 3-HR: 1.96; 95% CI: 1.64–2.34) and cardiovascular diseases [CVDs] (tertile 2-HR: 1.40; 95% CI: 1.09–1.79; tertile 3-HR: 2.00; 95% CI: 1.47–2.73). Similarly, compared with the subjects in WC tertile 1, the subjects in tertiles 2 and 3 were at a higher risk of mortality from all-cause (tertile 2-HR: 1.15; 95% CI: 1.00–1.31; tertile 3-HR: 1.39; 95% CI: 1.15–1.67) and CVD (tertile 2-HR: 1.48; 95% CI: 1.14–1.93; tertile 3-HR: 1.74; 95% CI: 1.26–2.42). Restricted cubic spline analyses revealed an S-shaped and linear dose-relationship between WtHR and WC with all-cause mortality. Moreover, a WtHR&gt; 0.58 or a WC &gt; 0.98m was shown to be a risk factor for all-cause mortality.ConclusionsCentral obesity was significantly associated with increased risk of all-cause and CVD-related mortality, especially heart diseases-related mortality, even among normal weight adults. In addition to weight control, guideline designer should provide recommendations for people to decrease abdominal fat accumulation, in their effort to reduce mortality risk in later life.
Relationship Between Dental Caries and Erosive Tooth Wear in Adolescents
Authors: Weber Megan L. , Søvik Jenny Bogstad , Mulic Aida , Deeley Kathleen , Modesto Adriana , Tveit Anne B. , Vieira Alexandre R. 
Published: January 2022

BackgroundOur aim was to investigate the relationship between caries experience and erosive tooth wear in adolescents.MethodsWe compared the Decayed, Missing, and Filled Teeth (dmft/DMFT) data of 795 adolescents to their erosive tooth wear scores using diet as a covariate and determined whether dental caries and erosive tooth wear scores are associated with each other, using linear regression analysis. Diet data and oral hygiene habits were collected using self-reported surveys and erosive tooth wear scores were previously collected. We also compared patients' genotypes and phenotypes and looked for an association between erosive tooth wear experience and different single nucleotide polymorphisms (SNPs). A Bonferroni correction was implemented to correct multiple comparisons. Two-group comparisons were made depending on the phenotype definitions implemented, and both chi-square and linear regression analyses were used to the test association between genetic variants and caries definitions. All covariates were included in each model.ResultsFor four SNPs (rs17159702, rs10246939, rs1800972, and rs1676303), there was an association between a spike in caries experience of DMFT 4 or more between two time points and increased frequency of fruit juice intake. A fifth SNP rs2860216 was shown to be a protective factor against a caries spike when associated with more frequent yogurt consumption. We did not find significant associations between our dental caries phenotypes or our demographic data and erosive tooth wear status in our linear regression.ConclusionsDental caries and erosive tooth wear are two diseases that differ in mechanism and heritability.
Cognitive and Linguistic Effects of Working Memory Training in Children With Corresponding Deficits
Authors: Pauls Laura J. , Archibald Lisa M. D. 
Published: January 2022

Working memory training has been found to result in improvements on tasks similar to those involved in the training (near transfer) but show limited impact on everyday skills such as language or academic abilities (far transfer). Previous research has largely focused on those with a broad range of skills, and examined group level responses. This study uses a single subject design to examine the effect of working memory training on both working memory and related domains in children with working memory impairment. Seven children (8–11 years old) with a working memory impairment completed 20 sessions of computerized working memory intervention. Data revealed near transfer for all participants. Evidence of far transfer to improvements in language, reading, or math was observed for approximately half of the participants on individual measures. Three participants showed convincing but modest training effects across multiple measures. A combination of factors appeared to influence far transfer including age, training intensity, and baseline measures.
Implementation of Islanding Recognizing Technique for Wind Distributed Generations Considering Insignificant NDZ
Authors: Raza Safdar , Munir Hafiz Mudassir , Shafique Nouman , Amjad Wajiha , Bajaj Mohit , Alghaythi Mamdouh L. 
Published: January 2022

The incorporation of distributed energy resources (DERs) into the electricity grid yields environmental, technical, and economic benefits. However, in addition to the benefits, the widespread use of DERs causes technical issues. Islanding is a big concern in terms of equipment protection and personnel safety, and it should be detected as soon as possible. The proposed approach employs a passive islanding detection technique based on reactive power (Q). The Q was chosen following a comparison of five other indices. Comparative analysis reveals that Q has the highest sensitivity and accuracy for islanding recognition when compared to all other observed parameters. Different case studies have been performed considering the worst-case scenario to check the working efficiency of the proposed scheme that simply distinguishes the islanding conditions from non-islanding conditions, which include load, motor, and capacitor switching, various types of fault switching, DG tripping cases, and weak grid contribution. The proposed strategy is straightforward, with quick execution and simple implementation in the MATLAB/SIMULINK environment on the IEEE 1547-2018 generic test system. With a small non-detection zone, islanding is detected in 0.038 s.
Identification of Alternative Polyadenylation in Cyanidioschyzon merolae Through Long-Read Sequencing of mRNA
Authors: Schärfen Leonard , Zigackova Dagmar , Reimer Kirsten A. , Stark Martha R. , Slat Viktor A. , Francoeur Nancy J. , Wells Melissa L. , Zhou Lecong , Blackshear Perry J. , Neugebauer Karla M. , Rader Stephen D. 
Published: January 2022

Alternative polyadenylation (APA) is widespread among metazoans and has been shown to have important impacts on mRNA stability and protein expression. Beyond a handful of well-studied organisms, however, its existence and consequences have not been well investigated. We therefore turned to the deep-branching red alga, Cyanidioschyzon merolae, to study the biology of polyadenylation in an organism highly diverged from humans and yeast. C. merolae is an acidothermophilic alga that lives in volcanic hot springs. It has a highly reduced genome (16.5 Mbp) and has lost all but 27 of its introns and much of its splicing machinery, suggesting that it has been under substantial pressure to simplify its RNA processing pathways. We used long-read sequencing to assess the key features of C. merolae mRNAs, including splicing status and polyadenylation cleavage site (PAS) usage. Splicing appears to be less efficient in C. merolae compared with yeast, flies, and mammalian cells. A high proportion of transcripts (63%) have at least two distinct PAS’s, and 34% appear to utilize three or more sites. The apparent polyadenylation signal UAAA is used in more than 90% of cases, in cells grown in both rich media or limiting nitrogen. Our documentation of APA for the first time in this non-model organism highlights its conservation and likely biological importance of this regulatory step in gene expression.
The Identification of Two RNA Modification Patterns and Tumor Microenvironment Infiltration Characterization of Lung Adenocarcinoma
Authors: He Wan , Lin Gengpeng , Pan Chaohu , Li Wenwen , Shen Jing , Liu Yangli , Li Hui , Wu Dongfang , Lin Xuejia 
Published: January 2022

Background: RNA modification plays an important role in many diseases. A comprehensive study of tumor microenvironment (TME) characteristics mediated by RNA modification regulators will improve the understanding of TME immune regulation.Methods: We selected 26 RNA modification “writers” of lung adenocarcinoma (LUAD) samples and performed unsupervised clustering analysis to explore RNA modification patterns in LUAD. Differentially expressed genes (DEGs) with RNA modification patterns were screened to develop a “writers” of RNA modification score (WM score) system. The infiltration ratio of TME cell subsets was analyzed by CIBERSORT.Results: We identified two RNA modification modes showing different characteristics of overall survival (OS) and TME cell infiltration. According to WM score, LUAD patients were divided into a high-WM score group and a low-WM score group. High-scored patients had a poor prognosis and higher tumor mutation burden (TMB), they were more sensitive to four LUAD therapies (erlotinib, XA V939, gefitinib, and KU-55933) and more clinically responsive to PD-L1 treatment. Those with a low WM score showed higher stromal scores, ESTIMATE scores, and survival chance.Conclusion: Our work revealed the potential role of RNA modification patterns in TME, genetic variation, targeted inhibitor therapy, and immunotherapy. Identifying RNA modification pattern of LUAD patients help understand the characteristics of TME and may promote the development of immunotherapy strategies.
Whole-Exome Sequencing Implicates Neuronal Calcium Channel with Familial Atrial Fibrillation
Authors: Vad Oliver Bundgaard , Yan Yannan , Denti Federico , Ahlberg Gustav , Refsgaard Lena , Bomholtz Sofia Hammami , Santos Joana Larupa , Rasmussen Simon , Haunsø Stig , Svendsen Jesper Hastrup , Christophersen Ingrid Elizabeth , Schmitt Nicole , Olesen Morten Salling , Bentzen Bo Hjorth 
Published: January 2022

Background: Atrial Fibrillation (AF) is the most prevalent sustained cardiac arrhythmia, responsible for considerable morbidity and mortality. The heterogenic and complex pathogenesis of AF remains poorly understood, which contributes to the current limitation in effective treatments. We aimed to identify rare genetic variants associated with AF in patients with familial AF.Methods and results: We performed whole exome sequencing in a large family with familial AF and identified a rare variant in the gene CACNA1A c.5053G &gt; A which co-segregated with AF. The gene encodes for the protein variants CaV2.1-V1686M, and is important in neuronal function. Functional characterization of the CACNA1A, using patch-clamp recordings on transiently transfected mammalian cells, revealed a modest loss-of-function of CaV2.1-V1686M.Conclusion: We identified a rare loss-of-function variant associated with AF in a gene previously linked with neuronal function. The results allude to a novel link between dysfunction of an ion channel previously associated with neuronal functions and increased risk of developing AF.