bluuebunny/crossref_metadata_2025_split huggingface dataset:
Imputation to whole-genome sequence and its use in genome-wide association studies for pork colour traits in crossbred and purebred pigs
Authors: Heidaritabar Marzieh , Huisman Abe , Krivushin Kirill , Stothard Paul , Dervishi Elda , Charagu Patrick , Bink Marco C. A. M. , Plastow Graham S. 
Published: October 2022

Imputed whole-genome sequence (WGS) has been proposed to improve genome-wide association studies (GWAS), since all causative mutations responsible for phenotypic variation are expected to be present in the data. This approach was applied on a large number of purebred (PB) and crossbred (CB) pigs for 18 pork color traits to evaluate the impact of using imputed WGS relative to medium-density marker panels. The traits included Minolta A*, B*, and L* for fat (FCOL), quadriceps femoris muscle (QFCOL), thawed loin muscle (TMCOL), fresh ham gluteus medius (GMCOL), ham iliopsoas muscle (ICOL), and longissimus dorsi muscle on the fresh loin (FMCOL). Sequence variants were imputed from a medium-density marker panel (61K for CBs and 50K for PBs) in all genotyped pigs using BeagleV5.0. We obtained high imputation accuracy (average of 0.97 for PBs and 0.91 for CBs). GWAS were conducted for three datasets: 954 CBs and 891 PBs, and the combined CBs and PBs. For most traits, no significant associations were detected, regardless of panel density or population type. However, quantitative trait loci (QTL) regions were only found for a few traits including TMCOL Minolta A* and GMCOL Minolta B* (CBs), FMCOL Minolta B*, FMCOL Minolta L*, and ICOL Minolta B* (PBs) and FMCOL Minolta A*, FMCOL Minolta B*, GMCOL Minolta B*, and ICOL Minolta B* (Combined dataset). More QTL regions were identified with WGS (n = 58) relative to medium-density marker panels (n = 22). Most of the QTL were linked to previously reported QTLs or candidate genes that have been previously reported to be associated with meat quality, pH and pork color; e.g., VIL1, PRKAG3, TTLL4, and SLC11A1, USP37. CTDSP1 gene on SSC15 has not been previously associated with meat color traits in pigs. The findings suggest any added value of WGS was only for detecting novel QTL regions when the sample size is sufficiently large as with the Combined dataset in this study. The percentage of phenotypic variance explained by the most significant SNPs also increased with WGS compared with medium-density panels. The results provide additional insights into identification of a number of candidate regions and genes for pork color traits in different pig populations.
MBD2 mediates Th17 cell differentiation by regulating MINK1 in Th17-dominant asthma
Authors: Chen Zhifeng , Shang Yulin , Yuan Yu , He Yi , Wasti Binaya , Duan Wentao , Ouyang Ruoyun , Jia Jingsi , Xiao Bing , Zhang Dongshan , Zhang Xiufeng , Li Jianmin , Chen Bolin , Liu Yi , Zeng Qingping , Ji Xiaoying , Ma Libing , Liu Shaokun , Xiang Xudong 
Published: October 2022

Objectives: .Asthma is a highly heterogeneous disease, and T-helper cell type 17 (Th17) cells play a pathogenic role in the development of non-T2 severe asthma. Misshapen like kinase 1 (MINK1) is involved in the regulation of Th17 cell differentiation, but its effect on severe asthma remains unclear. Our previous studies showed that methyl-CpG binding domain protein 2 (MBD2) expression was significantly increased in patients with Th17 severe asthma and could regulate Th17 cell differentiation. The aim of this study was to investigate how MBD2 interacts with MINK1 to regulate Th17 cell differentiation in Th17-dominant asthma.Materials and methods: Female C57BL/6 mice and bronchial epithelial cells (BECs) were used to establish mouse and cell models of Th17-dominant asthma, respectively. Flow cytometry was used to detect Th17 cell differentiation, and the level of IL-17 was detected by enzyme-linked immunosorbent assay (ELISA). Western blot and quantitative real-time PCR (qRT-PCR) were used to detect MBD2 and MINK1 expression. To investigate the role of MBD2 and MINK1 in Th17 cell differentiation in Th17-dominant asthma, the MBD2 and MINK1 genes were silenced or overexpressed by small interfering RNA and plasmid transfection.Results: Mouse and BEC models of Th17-dominant asthma were established successfully. The main manifestations were increased neutrophils in BALF, airway hyperresponsiveness (AHR), activated Th17 cell differentiation, and high IL-17 levels. The expression of MBD2 in lung tissues and BECs from the Th17-dominant asthma group was significantly increased, while the corresponding expression of MINK1 was significantly impaired. Through overexpression or silencing of MBD2 and MINK1 genes, we have concluded that MBD2 and MINK1 regulate Th17 cell differentiation and IL-17 release. Interestingly, MBD2 was also found to negatively regulate the expression of MINK1.Conclusion: Our findings have revealed new roles for MBD2 and MINK1, and provide new insights into epigenetic regulation of Th17-dominant asthma, which is dominated by neutrophils and Th17 cells. This study could lead to new therapeutic targets for patients with Th17-dominant asthma.
Identifying enhancer-driven subtype-specific prognostic markers in breast cancer based on multi-omics data
Authors: Zhao Hongying , Zhang Siwen , Yin Xiangzhe , Zhang Caiyu , Wang Lixia , Liu Kailai , Xu Haotian , Liu Wangyang , Bo Lin , Lin Shihua , Feng Ke , Lin Lin , Fei Meiting , Ning Shangwei , Wang Li 
Published: October 2022

Breast cancer is a cancer of high complexity and heterogeneity, with differences in prognosis and survival among patients of different subtypes. Copy number variations (CNVs) within enhancers are crucial drivers of tumorigenesis by influencing expression of their targets. In this study, we performed an integrative approach to identify CNA-driven enhancers and their effect on expression of target genes in four breast cancer subtypes by integrating expression data, copy number data and H3K27ac data. We identified 672, 555, 531, 361 CNA-driven enhancer-gene pairs and 280, 189, 113 and 98 CNA-driven enhancer-lncRNA pairs in the Basal-like, Her2, LumA and LumB subtypes, respectively. We then reconstructed a CNV-driven enhancer-lncRNA-mRNA regulatory network in each subtype. Functional analysis showed CNA-driven enhancers play an important role in the progression of breast cancer subtypes by influencing P53 signaling pathway, PPAR signaling pathway, systemic lupus erythematosus and MAPK signaling pathway in the Basal-like, Her2, LumA and LumB subtypes, respectively. We characterized the potentially prognostic value of target genes of CNV-driven enhancer and lncRNA-mRNA pairs in the subtype-specific network. We identified MUM1 and AC016876.1 as prognostic biomarkers in LumA and Basal-like subtypes, respectively. Higher expression of MUM1 with an amplified enhancer exhibited poorer prognosis in LumA patients. Lower expression of AC016876.1 with a deleted enhancer exhibited poorer survival outcomes of Basal-like patients. We also identified enhancer-related lncRNA-mRNA pairs as prognostic biomarkers, including AC012313.2-MUM1 in the LumA, AC026471.4-PLK5 in the LumB, AC027307.2-OAZ1 in the Basal-like and AC022431.1-HCN2 in the Her2 subtypes. Finally, our results highlighted target genes of CNA-driven enhancers and enhancer-related lncRNA-mRNA pairs could act as prognostic markers and potential therapeutic targets in breast cancer subtypes.
Development and validation of Chronic Kidney Disease Knowledge, Attitude, and Practices (CKD-KAP) questionnaire
Authors: Tariq Muhammad Haseeb , Sulaiman Syed Azhar Syed , Farrukh Muhammad Junaid , Goh Khang Wen , Ming Long Chiau 
Published: October 2022

BackgroundChronic Kidney Disease (CKD) is a complex condition leading to loss of kidney function. The objective of this study was to develop and validate a Knowledge, Attitude, and Practice questionnaire on CKD (CKD-KAP) among practicing physicians in Pakistan since no validated tool was available for the said purpose.MethodsThe study consisted of four phases with phase-I focusing on literature review, phase II was the actual questionnaire development phase, face and content validity was determined in phase III, and finally pilot testing was performed in phase IV to determine validity and reliability. The development phase encompassed a thorough review of literature, focus-group discussion, expert review, and evaluation. The validation phase consisted of content validity, face validity, construct validity, convergent validity, and reliability. The pilot testing was performed by studying the KAP of 100 practicing physicians in tertiary care hospitals in Pakistan. The knowledge section of the validation phase utilized Item Response Theory (IRT) analysis. The attitude and practices sections utilized Exploratory Factor Analysis (EFA) theory. The reliability analysis utilized Cronbach’s alpha and correlations.ResultsThe CKD-KAP questionnaire had three main sections: knowledge, attitude, and practice. During the validation, IRT analysis was performed on knowledge, which focused on the measure of the coefficient of discrimination and difficulty of the items; 40 out of 41 knowledge items have both discrimination and difficulty coefficients within an acceptable range. The EFA model was also fitted in the attitude and practices section, and scree plot and Eigenvalues suggested three and four dimensions within the attitude and practices section. The factor loading of all items was found to be acceptable except for one item in attitude which was deleted. The convergent validity demonstrated a significant association between all three sections except knowledge and practices. The reliability (internal consistency) analysis demonstrated Cronbach’s alpha values above 0.7 and significant inter-item correlation. The final model of CKD-KAP had 40 knowledge, 13 attitude, and 10 practice items with a combination of both positive as well as negative questions and statements.ConclusionsThe CKD-KAP was found to be psychometrically valid and reliable, hence can be used to determine the knowledge, attitude, and practices of physicians toward chronic kidney disease.
Application of lymphoplasmapheresis in the treatment of severe myasthenia gravis
Authors: Duan Weiwei , Zhou Hao , Dong Xiaohua , Li Bijuan , Li Yi , Cai Haobing , Zhou Qian , Ouyang Song , Yin Weifan , Yang Huan 
Published: October 2022

BackgroundLymphoplasmapheresis (LPE) is a treatment that combines traditional plasma exchange and lymphocyte removal technique. It has been applied to treat a variety of autoimmune diseases, but its application value in the treatment of severe myasthenia gravis (MG) is not yet clear. Therefore, the aim of this study was to investigate the efficacy and safety of LPE in severe MG.MethodsClinical data of 123 severe patients with MG (Myasthenia Gravis Foundation of America Clinical Classification, Class IV) who received LPE treatment were included in a retrospective analysis. Efficacy was evaluated by the change of Quantitative Myasthenia Gravis score (QMGS) before and after treatment. Univariate and multivariate logistic regression analysis was used to explore clinical factors affecting efficacy.ResultsA total of 220 replacements were performed in 123 patients, with an average of 1.79 replacements per patient. The overall safety of LPE was good, and no serious adverse reactions occurred. After treatment, the mean QMGS of patients decreased significantly, from 23.40 ± 4.25 points before treatment to 17.93 ± 5.61 points after treatment, a decrease of 5.47 ± 4.16 points. 75.6% of patients experienced remission of clinical symptoms. During a 2-month follow-up of 64 patients, a progressive improvement in QMGS was found. Each muscle group involved in MG responded well to LPE treatment. In addition, LPE significantly reduced the levels of AChR-Ab and inflammatory cytokines in patients. Age ≥ 50 years and co-infection were unfavorable factors affecting the efficacy.ConclusionsIn this study cohort, LPE is safe for the treatment of severe MG and achieves good treatment outcome with fewer replacements. In patients with MG, the avoidance and timely control of infection are necessary. Our study provides a potential new treatment option for severe MG.
Regulation of sleep disorders in patients with traumatic brain injury by intestinal flora based on the background of brain-gut axis
Authors: Zhanfeng Niu , Liang Wu , Jing Kang , Jinbo Bai , Yanjun Chen , Hechun Xia 
Published: October 2022

ObjectiveThis study investigates whether people with sleep disorders following traumatic brain injury exhibit altered intestinal flora. The changes may allow us to gain a better understanding of the role of intestinal flora in patients with sleep disorders after traumatic brain injury, which may give us insights into curing the sleep disorder after traumatic brain injury (TBI).MethodWe analyzed the intestinal microbial colony structure in the feces of the 28 patients in the normal sleep group and the sleep disorder group by 16SrDNAsequencing technology. The bioinformatics method was used to analyze the intestinal flora change in the v3-v4 region of patients with biorhythm disorder and to observe the difference between the two groups.ResultsGroup grouping comparison and analysis of the evolutionary cladistic map showed the intestinal flora of patients with normal sleep after TBI was mainly Bacilli and Lactobacillales, while that of patients with sleep disorders was mainly Lachnospiraceae and Bacteroidales. The histogram of group value distribution by grouping comparison and analysis showed that Lachnospiraceae, Bacteroidales, Bacteroidia, and Bacteroidetes were dominant in the sleep disorder group. A relative abundance map of species with significant differences by group grouping comparison showed the main manifestations of intestinal flora are Firmicutes, Bacilli, Lactobacillales, Streptococcaceae, and Bacteroidetes. The normal sleep group was dominated by Bacilli, Lactobacillales, Streptococcus, and Veillonella, while in the sleep disorder group, Lachnospiraceae, Bacteroidales, Bacteroidia, and Bacteroidetes were the main species. It was found that there were also significant differences in intestinal flora abundance between the two groups after TBI. After statistics processing, it was compared with the normal sleep group, Lactobacillus, Streptococcus, Oribacterium and Rothia, Actinomyces, Streptophyta, TM7-3 bacteria, and Serratia, showing a significant reduction in the sleep disorder group (P &lt; 0.05). However, Odoribacter, Lachnospiraceae, and Bilophila increased significantly (P &lt; 0.05).ConclusionThe sleep disorders of patients after TBI can be closely related to intestinal flora disturbance, and its internal mechanism needs further study. Intestinal flora has the potential to be a new therapeutic target.
In vitro neutrophil migration is associated with inhaled corticosteroid treatment and serum cytokines in pediatric asthma
Authors: Lemmel Solveig , Weckmann Markus , Wohlers Anna , Jirmo Adan Chari , Grychtol Ruth , Ricklefs Isabell , Nissen Gyde , Bachmann Anna , Singh Shantanu , Caicedo Juan , Bahmer Thomas , Hansen Gesine , Von Mutius Erika , Rabe Klaus F. , Fuchs Oliver , Dittrich Anna-Maria , Schaub Bianca , Happle Christine , Carpenter Anne E. , Kopp Matthias Volkmar , Becker Tim ,   the ALLIANCE Study Group as part of the German Centre for Lung Research (DZL)
Published: October 2022

Background: Different asthma phenotypes are driven by molecular endotypes. A Th1-high phenotype is linked to severe, therapy-refractory asthma, subclinical infections and neutrophil inflammation. Previously, we found neutrophil granulocytes (NGs) from asthmatics exhibit decreased chemotaxis towards leukotriene B4 (LTB4), a chemoattractant involved in inflammation response. We hypothesized that this pattern is driven by asthma in general and aggravated in a Th1-high phenotype.Methods: NGs from asthmatic nd healthy children were stimulated with 10 nM LTB4/100 nM N-formylmethionine-leucyl-phenylalanine and neutrophil migration was documented following our prior SiMA (simplified migration assay) workflow, capturing morphologic and dynamic parameters from single-cell tracking in the images. Demographic, clinical and serum cytokine data were determined in the ALLIANCE cohort.Results: A reduced chemotactic response towards LTB4 was confirmed in asthmatic donors regardless of inhaled corticosteroid (ICS) treatment. By contrast, only NGs from ICS-treated asthmatic children migrate similarly to controls with the exception of Th1-high donors, whose NGs presented a reduced and less directed migration towards the chemokines. ICS-treated and Th1-high asthmatic donors present an altered surface receptor profile, which partly correlates with migration.Conclusions: Neutrophil migration in vitro may be affected by ICS-therapy or a Th1-high phenotype. This may be explained by alteration of receptor expression and could be used as a tool to monitor asthma treatment.
Physical activity and mental health in sports university students during the COVID-19 school confinement in Shanghai
Authors: Wang Yufei , Li Youqiang 
Published: October 2022

BackgroundIn 2022, Shanghai was seriously affected by the coronavirus disease 2019 (COVID-19) pandemic. The government implemented citywide static management for 2 months, as well as all universities in Shanghai, which changed the normal learning and living style of sports students and led to a decline in physical activity level. As the physical activity has a strong correlation with mental health, this study aimed to investigate the current state of physical activity (PA) and mental health of the students in Shanghai University of Sport. It will try to reveal the correlation between PA and depressive symptoms, anxiety symptoms, fear of COVID-19 and smartphone addiction.MethodsA cross-sectional survey was conducted on a random sample of 400 students who came from six different majors in May 2022 at the Shanghai University of Sport. Respondents completed the International Physical Activity Questionnaire Short Form (IPAQ-SF), the Chinese version of the 9-item Patient Health Questionnaire (PHQ-9), the Chinese version of the Generalized Anxiety Disorder Scale (GAD-7), the Chinese version of the COVID-19 Fear Scale (FCV- 19S), and the Smartphone Addiction Scale (SAS-SV). Demographics, PA, depressive symptoms, anxiety symptoms, fear of COVID-19, and smartphone addiction were compared. A binary logistic regression model was used for the further analysis.ResultsA total of 376 college students were included in the final analysis. Binary logistics analysis showed that moderate physical activity (MPA) was negatively correlated with depression (OR = 0.95, 95%CI = 0.93–0.98), anxiety (OR = 0.97, 95%CI = 0.95–0.99), fear of COVID 19(OR = 0.99, 95%CI = 0.98–0.99)and smartphone addiction (OR = 0.94, 95%CI = 0.9–0.98) (all P &lt; 0.05). Sedentary behavior was positively correlated with smartphone addiction (OR = 1.01, P &lt; 0.01, 95%CI = 1.001–1.004).ConclusionThere was an association between the presence of MPA and depressive symptoms, anxiety symptoms, fear of COVID-19, smartphone addiction, and sedentary behavior associated with smartphone addiction levels. Clarifying the causal relationship between PA and mental health will require further research.
Key determinants to school breakfast program implementation in Philadelphia public schools: Implications for the role of SNAP-Ed
Authors: Fornaro Elisabeth G. , McCrossan Erin , Hawes Peter , Erdem Ebru , McLoughlin Gabriella Maria 
Published: October 2022

BackgroundPolicies addressing food insecurity are only effective if they are implemented successfully, serving those most at risk. Universal school meals provide a key intervention to schools that serve predominantly low-income families by providing free school breakfast and lunch to all. Unfortunately, low uptake of such provisions among students is concerning especially regarding school breakfast, warranting key implementation support for schools to ensure student nutrition needs are met. Thus, the purpose of this study was to evaluate the determinants of implementing two different school breakfast programs and pragmatic strategies for serving breakfast in ways that maximize student participation.MethodsA qualitative study was conducted between 2018 and 2020 within the School District of Philadelphia (SDP) comprising surveys, interviews, and observations to assess contextual determinants of two distinctive breakfast models: Breakfast in the Classroom (BIC) and Cafeteria after the Bell (CAB). Principals and lead kitchen staff completed surveys to assess determinants of breakfast model adoption. Principals, lead kitchen staff, classroom teachers, climate (i.e., social emotional wellbeing), and facilities staff subsequently participated in interviews to discuss implementation determinants (i.e., facilitators and challenges) and strategies for maximizing student participation. Observations provided rich data to triangulate interviews and survey data. Survey data were analyzed using frequency analysis, and observation and interview data were analyzed through thematic analysis. Presentation of themes was framed by the Consolidated Framework for Implementation Research.ResultsResults highlighted several positive determinants to participation including addressing student and family needs, making data-informed decisions, and providing hot meals and fruit based on student tastes. Negative determinants to implementation comprised challenges to SNAP-Ed-funded policy changes to promote student breakfast participation, lack of communication between administration, and staff and turnover among food service staff. Strategies included modifying school entrance procedures and combining breakfast with other education-related tasks to minimize instructional time lost through breakfast after the bell schedules.DiscussionData highlight the need to include implementation partner expertise when designing interventions for increasing reach and effectiveness of school meal programs. Future research that directly tests implementation strategies and key outcomes of reach/participation, among others, is critical to bridging the policy to practice gap in school nutrition programs.
Characteristics of Graves' disease in children and adolescents in Nanjing: A retrospective investigation study
Authors: Xie Hang , Chen Dandan , Zhang Ju , Yang Ruize , Gu Wei , Wang Xu 
Published: October 2022

ObjectiveThis cross-sectional study analyzed the clinical characteristics of newly diagnosed Graves' disease (GD) in children and adolescents to provide clinical evidence for the early diagnosis of GD.MethodFrom 2013 to 2019, information on children and adolescents with newly diagnosed GD admitted to the Department of Endocrinology, Children's Hospital of Nanjing Medical University, was collected, including clinical features and laboratory tests. The data were summarized and statistically analyzed.ResultThis study included 204 cases of newly diagnosed GD, with 158 females and 46 males. The average age at initial diagnosis was 8.9 ± 2.9 years. A total of 132 cases (64.7%) had symptoms before puberty, and 72 cases (35.3%) had symptoms during puberty. Goiter was detected in 193 cases (94.6%). There were 140 cases (68.6%) of exophthalmos, and 21.4% (30/140) were infiltrative. At initial diagnosis, 10 cases (4.9%) reported leukopenia, 18 cases (8.8%) reported neutropenia, and 15 cases (7.4%) reported mild anemia. There was 1 (0.5%) case of thrombocytopenia and 1 (0.5%) case of agranulocytosis. Fifty-four cases (26.5%) had impaired liver function.ConclusionGD is more common in female children and adolescents. Parents may ignore their children's hypermetabolic symptoms in the early stages of GD. Routine blood and liver function tests are recommended at initial diagnosis to exclude abnormal hemogram and liver function.