bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physical Activity and Diet in a Global Pandemic: An Investigation of the Impact of COVID-19 on Factors Relevant for Musculoskeletal Health at Two Different Stages of the Lifecourse
Authors: Bevilacqua Gregorio , D’Angelo Stefania , Linaker Cathy , Paul Alice , Bloom Ilse , Zhang Jean , Laskou Faidra , Cooper Cyrus , Ward Kate A. , Walker-Bone Karen , Dennison Elaine M. 
Published: May 2022

BackgroundPhysical activity, nutrition and other lifestyle factors play important roles in maintaining musculoskeletal health. The coronavirus disease (COVID-19) originated in late 2019, spread globally to be declared a pandemic by the World Health Organisation in March 2020, and led to widespread behaviour change. The aim of this study was to use two existing cohorts, the Hertfordshire Cohort Study (HCS) and Health and Employment After Fifty Study (HEAF), to understand how wave one of the COVID-19 pandemic impacted lifestyle factors associated with musculoskeletal health in the UK.Methods125 eligible participants, 65 males and 60 females (drawn from the HCS study, median (IQR) age 84.3 (82.4-86.6) years, all Caucasian, and community dwelling) were contacted by telephone and asked to complete a questionnaire administered by a trained researcher. Data collection occurred over the period July 2020 to February 2021. 2469 participants, 1086 men and 1383 women (drawn from the HEAF study, median age 65.7 (62.0-69.3) years, mostly Caucasian and community dwelling) completed an online questionnaire in March 2021.ResultsIn HCS, 47% respondents reported being less physically active than before the pandemic (and only 5% more so), 27% said they consumed less alcohol compared to pre-pandemic times (and only 3% more so), and 18% reported eating less than before, although quality of diet was generally unchanged over this timeframe surveyed. In HEAF, 44% participants said they were less active than before the pandemic, while 17% reported being more active. The majority of participants reported no changes in alcohol consumption and diet; however, 19% said they drank more than before (32% of which was above recommended levels), 16% said their diet was less healthy, and 19% reported eating more than before.ConclusionWe have reported the experience of the first wave of the COVID-19 pandemic among participants of two Caucasian community dwelling UK cohorts, highlighting the impact of the pandemic on lifestyle factors associated with musculoskeletal health. Changed physical activity levels were reported in a high proportion of respondents in both studies; an investigation of reversibility of these changes is required.
Single Nucleotide Polymorphism Effects on Lamb Fecal Egg Count Estimated Breeding Values in Progeny-Tested Katahdin Sires
Authors: Notter David R. , Heidaritabar Marzieh , Burke Joan M. , Shirali Masoud , Murdoch Brenda M. , Morgan James L. M. , Morota Gota , Sonstegard Tad S. , Becker Gabrielle M. , Spangler Gordon L. , MacNeil Michael D. , Miller James E. 
Published: May 2022

Estimated breeding values (EBV) for fecal egg counts (FEC) at 42–90 days of age (WFEC) and 91–150 days of age (PFEC) for 84 progeny-tested Katahdin sires were used to identify associations of deregressed EBV with single-nucleotide polymorphisms (SNP) using 388,000 SNP with minor-allele frequencies ≥0.10 on an Illumina high-density ovine array. Associations between markers and FEC EBV were initially quantified by single-SNP linear regression. Effects of linkage disequilibrium (LD) were minimized by assigning SNP to 2,535 consecutive 1-Mb bins and focusing on the effect of the most significant SNP in each bin. Bonferroni correction was used to define bin-based (BB) genome- and chromosome-wide significance. Six bins on chromosome 5 achieved BB genome-wide significance for PFEC EBV, and three of those SNP achieved chromosome-wide significance after Bonferroni correction based on the 14,530 total SNP on chromosome 5. These bins were nested within 12 consecutive bins between 59 and 71 Mb on chromosome 5 that reached BB chromosome-wide significance. The largest SNP effects were at 63, 67, and 70 Mb, with LD among these SNP of r2 ≤ 0.2. Regional heritability mapping (RHM) was then used to evaluate the ability of different genomic regions to account for additive variance in FEC EBV. Chromosome-level RHM indicated that one 500-SNP window between 65.9 and 69.9 Mb accounted for significant variation in PFEC EBV. Five additional 500-SNP windows between 59.3 and 71.6 Mb reached suggestive (p &lt; 0.10) significance for PFEC EBV. Although previous studies rarely identified markers for parasite resistance on chromosome 5, the IL12B gene at 68.5 Mb codes for the p40 subunit of both interleukins 12 and 23. Other immunoregulatory genes are also located in this region of chromosome 5, providing opportunity for additive or associative effects.
Clinical, Virological and Immunological Subphenotypes in a Cohort of Early Treated HIV-Infected Children
Authors: Domínguez-Rodríguez Sara , Tagarro Alfredo , Foster Caroline , Palma Paolo , Cotugno Nicola , Zicari Sonia , Ruggiero Alessandra , de Rossi Anita , Dalzini Annalisa , Pahwa Savita , Rinaldi Stefano , Nastouli Eleni , Marcelin Anne-Geneviève , Dorgham Karim , Sauce Delphine , Gartner Kathleen , Rossi Paolo , Giaquinto Carlo , Rojo Pablo 
Published: May 2022

BackgroundIdentifying subphenotypes within heterogeneous diseases may have an impact in terms of therapeutic options. In this study, we aim to assess different subphenotypes in children living with human immunodeficiency virus (HIV-1), according to the clinical, virological, and immunological characteristics.MethodsWe collected clinical and sociodemographic data, baseline viral load (VL), CD4 and CD8 count and percentage, age at initiation of ART, HIV DNA reservoir size in peripheral blood mononuclear cells (PBMCs), cell-associated RNA (CA-RNA), ultrasensitive VL, CD4 subsets (T effector CD25+, activated memory cells, Treg cells), humoral-specific HIV response (T-bet B cells), innate response (CD56dim natural killer (NK) cells, NKp46+, perforin), exhaustion markers (PD-1, PD-L1, DNAM), CD8 senescence, and biomarkers for T-lymphocyte thymic output (TREC) and endothelial activation (VCAM). The most informative variables were selected using an unsupervised lasso-type penalty selection for sparse clustering. Hierarchical clustering was performed using Pearson correlation as the distance metric and WARD.D2 as the clustering method. Internal validation was applied to select the best number of clusters. To compare the characteristics among clusters, boxplot and Kruskal Wallis test were assessed.ResultsThree subphenotypes were discovered (cluster1: n=18, 45%; cluster2: n=11, 27.5%; cluster3: n=11, 27.5%). Patients in cluster1 were treated earlier, had higher baseline %CD4, low HIV reservoir size, low western blot score, higher TREC values, and lower VCAM values than the patients in the other clusters. In contrast, cluster3 was the less favorable. Patients were treated later and presented poorer outcomes with lower %CD4, and higher reservoir size, along with a higher percentage of CD8 immunosenescent cells, lower TREC, higher VCAM cytokine, and a higher %CD4 PD-1. Cluster2 was intermediate. Patients were like those of cluster1, but had lower levels of t-bet expression and higher HIV DNA reservoir size.ConclusionsThree HIV pediatric subphenotypes with different virological and immunological features were identified. The most favorable cluster was characterized by a higher rate of immune reconstitution and a slower disease progression, and the less favorable with more senescence and high reservoir size. In the near future therapeutic interventions for a path of a cure might be guided or supported by the different subphenotypes.
A Somatic Mutation Signature Predicts the Best Overall Response to Anti-programmed Cell Death Protein-1 Treatment in Epidermal Growth Factor Receptor/Anaplastic Lymphoma Kinase-Negative Non-squamous Non-small Cell Lung Cancer
Authors: Peng Jie , Xiao Lushan , Zou Dan , Han Lijie 
Published: May 2022

BackgroundWe aimed to exploit a somatic mutation signature (SMS) to predict the best overall response to anti-programmed cell death protein-1 (PD-1) therapy in non-small cell lung cancer (NSCLC).MethodsTumor samples of 248 patients with epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK)-negative non-squamous NSCLC treated with anti-PD-1 were molecularly tested by targeted next-generation sequencing or whole exome sequencing. On the basis of machine learning, we developed and validated a predictive model named SMS using the training (n = 83) and validation (n = 165) cohorts.ResultsThe SMS model comprising a panel of 15 genes (TP53, PTPRD, SMARCA4, FAT1, MGA, NOTCH1, NTRK3, INPP4B, KMT2A, PAK1, ATRX, BCOR, KDM5C, DDR2, and ARID1B) was built to predict best overall response in the training cohort. The areas under the curves of the training and validation cohorts were higher than those of tumor mutational burden and PD-L1 expression. Patients with SMS-high in the training and validation cohorts had poorer progression-free survival [hazard ratio (HR) = 6.01, P &lt; 0.001; HR = 3.89, P &lt; 0.001] and overall survival (HR = 7.60, P &lt; 0.001; HR = 2.82, P &lt; 0.001) than patients with SMS-low. SMS was an independent factor in multivariate analyses of progression-free survival and overall survival (HR = 4.32, P &lt; 0.001; HR = 3.07, P &lt; 0.001, respectively).ConclusionThis study revealed the predictive value of SMS for immunotherapy best overall response and prognosis in EGFR/ALK-negative non-squamous NSCLC as a potential biomarker in anti-PD-1 therapy.
Exosome Mediated Cytosolic Cisplatin Delivery Through Clathrin-Independent Endocytosis and Enhanced Anti-cancer Effect via Avoiding Endosome Trapping in Cisplatin-Resistant Ovarian Cancer
Authors: Zhou Guannan , Gu Yuanyuan , Zhu Zhongyi , Zhang Hongdao , Liu Wei , Xu Beiying , Zhou Fangyue , Zhang Menglei , Hua Keqin , Wu Ligang , Ding Jingxin 
Published: May 2022

BackgroundOvarian carcinoma is one of the most common gynecologic malignancies, cisplatin resistance has become a key obstacle to the successful treatment of ovarian cancer because ovarian carcinomas are liable to drug resistance. To find an effective drug carrier is an urgent need.MethodsExosomes and loading-cisplatin exosomes are isolated using differential centrifugation and characterized by transmission, electron, nanoparticle tracking analysis. The anti-cancer effect of cisplatin was detected under the circumstance of delivered by exosomes or without exosomes in vitro and in vivo. Using proteome analysis and bioinformatics analysis, we further discovered the pathways in exosomes delivery process. We employed a con-focal immunofluorescence analysis, to evaluate the effects of milk-exosomes deliver the cisplatin via avoiding endosomal trapping.ResultsExosomes and exosome-cisplatin were characterized including size, typical markers including CD63, Alix and Tsg101. The anti-cancer effect of cisplatin was enhanced when delivered by exosome in vitro and in vivo. Mechanistic studies shown that exosomes deliver cisplatin mostly via clathrin-independent endocytosis pathway. Exosomes deliver cisplatin into cisplatin-resistant cancer cells clathrin-independent endocytosis and enhance the anti-cancer effect through avoiding endosome trapping.ConclusionCisplatin could be delivered by exosome through clathrin-independent endocytosis, and could evade the endosome trapping, diffused in the cytosol evenly. Our study clarifies the mechanism of exosomes mediated drug delivery against resistant cancer, indicates that exosomes can be a potential nano-carrier for cisplatin against cisplatin resistant ovarian cancer, which validates and enriches the theory of intracellular exosome trafficking.
Utility of Baseline Transcriptomic Analysis of Rheumatoid Arthritis Synovium as an Indicator for Long-Term Clinical Outcomes
Authors: Anaparti Vidyanand , Wiens Dana , O'Neil Liam J. , Hubbard Erika , Robl Robert , Smolik Irene , Hitchon Carol , Lipsky Peter E. , El-Gabalawy Hani 
Published: May 2022

Objective:Rheumatoid arthritis is a chronic inflammatory autoimmune disease that can lead to synovial damage, persistent joint pain, and functional disability. Our objective was to evaluate baseline synovial transcriptome from early inflammatory arthritis patients (EIA) and identify pretreatment biomarkers that could potentially provide insights into long-term functional outcomes of rheumatoid arthritis (RA).MethodsSynovial biopsies from clinically inflamed knee joints were procured from either 17 EIA patients before initiation of disease modifying anti-rheumatic drug (DMARD) therapy (DMARD-naïve EIA) using the minimally invasive closed needle biopsy technique or advanced RA patients undergoing arthroplasty. Affymetrix Human Genome U133 Plus 2 microarray platform was used to profile the synovial transcriptome. The cohort was followed clinically for a median of 12.3 years, and patient data was collected at each visit. Short-term and long-term clinical outcomes were determined by assessing RA-associated clinical parameters Statistical adjustments were made to account for asynchronous clinical visits and duration of follow up.ResultsBased on the transcriptomic analysis, we identified 5 differentially expressed genes (DEGs), including matrix metalloproteinase (MMP)-1 (fibroblast collagenase) and MMP-3 (stromelysin-1) in DMARD-naïve EIA patients, relative to advanced RA patients (q &lt; 0.05). Dichotomous expression of MMP-1 and MMP-3 mRNA and protein was confirmed by qPCR and immunohistochemistry respectively, based on which DMARD-naïve EIA subjects were classified as MMP-high or MMP-low. Hierarchical clustering of transcriptomic data identified 947 DEGs between MMP-high and MMP-low cohorts. Co-expression and IPA analysis of DEGs in the MMP-high cohort showed an enrichment of genes that participated in metabolic or biochemical functions and intracellular immune signaling were regulated through NF-κB and β-catenin complexes and correlated with markers of systemic inflammation. Analysis of short-term clinical outcomes in MMP-high cohort showed a significant reduction in the DAS-CRP scores relative to baseline (P &lt;0.001), whereas area under the curve analyses of modified HAQ (mHAQ) scores correlated negatively with baseline MMP-1 (R = −0.59, P = 0.03). Further, longitudinal mHAQ scores, number of swollen joints, number of DMARDs and median follow-up duration appeared to be higher in MMP-low cohort.ConclusionOverall, our results indicate that the gene expression profiling of synovial biopsies obtained at the DMARD-naive stage in patients with EIA categorizes them into subsets with varying degrees of inflammation and can predict the future of long-term clinical outcome.
Applying Information Gain to Explore Factors Affecting Small-Incision Lenticule Extraction: A Multicenter Retrospective Study
Authors: Liang Shuang , Ji Shufan , Liu Xiao , Chen Min , Lei Yulin , Hou Jie , Li Mengdi , Zou Haohan , Peng Yusu , Ma Zhixing , Liu Yuanyuan , Jhanji Vishal , Wang Yan 
Published: May 2022

PurposeThis retrospective study aimed to identify the key factors influencing postoperative refraction after small-incision lenticule extraction (SMILE) using information gain.MethodsThis study comprised 2,350 eyes of 1,200 patients who underwent SMILE using a Visumax 500-kHz femtosecond laser (Carl Zeiss Meditec AG) in three ophthalmic centers: Tianjin Eye Hospital (center A), Jinan Mingshui Eye Hospital (center B), and Qingdao Eye Hospital (center C). Anterior segment features, including corneal curvature and central corneal thickness (CCT), were obtained from Pentacam HR (Oculus, Wetzlar, Germany). Information gain was calculated to analyze the importance of features affecting postoperative refraction.ResultsPreoperative and postoperative mean spherical equivalent (SE) refraction were −5.00 (−6.13, −3.88) D and 0.00 (−0.25, 0.13) D, respectively. None of the patients lost more than two lines of corrected distance visual acuity. The safety index was 1.32 ± 0.24, 1.03 ± 0.08, and 1.13 ± 0.16 in centers A, B, and C, respectively. The efficacy index was 1.31 ± 0.25, 1.02 ± 0.08, and 1.13 ± 0.17 in centers A, B, and C, respectively. At least 95% of the eyes were within ±1.00 D of the attempted correction. Postoperative refraction was related to preoperative spherical diopter refraction (r = 0.369, p &lt; 0.001), preoperative SE (r = 0.364, p &lt; 0.001), maximum lenticule thickness (r = −0.311, p &lt; 0.001), preoperative uncorrected distance visual acuity (r = 0.164, p &lt; 0.001), residual stromal thickness (r = 0.139, p &lt; 0.001), preoperative mean anterior corneal curvature (r = −0.127, p &lt; 0.001), preoperative flattest anterior corneal curvature (r = −0.122, p &lt; 0.001), nomogram (r = −0.100, p &lt; 0.001) and preoperative CCT (r = −0.058, p = 0.005).ConclusionsSMILE was considered a safe and effective procedure for correcting myopia. Based on information gain, postoperative refraction was influenced by preoperative mean anterior corneal curvature, CCT, refraction, and residual stromal thickness.
Shape Trumps Size: Image-Based Morphological Analysis Reveals That the 3D Shape Discriminates Intracranial Aneurysm Disease Status Better Than Aneurysm Size
Authors: Juchler Norman , Schilling Sabine , Bijlenga Philippe , Kurtcuoglu Vartan , Hirsch Sven 
Published: May 2022

BackgroundTo date, it remains difficult for clinicians to reliably assess the disease status of intracranial aneurysms. As an aneurysm's 3D shape is strongly dependent on the underlying formation processes, it is believed that the presence of certain shape features mirrors the disease status of the aneurysm wall. Currently, clinicians associate irregular shape with wall instability. However, no consensus exists about which shape features reliably predict instability. In this study, we present a benchmark to identify shape features providing the highest predictive power for aneurysm rupture status.Methods3D models of aneurysms were extracted from medical imaging data (3D rotational angiographies) using a standardized protocol. For these aneurysm models, we calculated a set of metrics characterizing the 3D shape: Geometry indices (such as undulation, ellipticity and non-sphericity); writhe- and curvature-based metrics; as well as indices based on Zernike moments. Using statistical learning methods, we investigated the association between shape features and aneurysm disease status. This processing was applied to a clinical dataset of 750 aneurysms (261 ruptured, 474 unruptured) registered in the AneuX morphology database. We report here statistical performance metrics [including the area under curve (AUC)] for morphometric models to discriminate between ruptured and unruptured aneurysms.ResultsThe non-sphericity index NSI (AUC = 0.80), normalized Zernike energies ZNsurf (AUC = 0.80) and the modified writhe-index W¯meanL1 (AUC = 0.78) exhibited the strongest association with rupture status. The combination of predictors further improved the predictive performance (without location: AUC = 0.82, with location AUC = 0.87). The anatomical location was a good predictor for rupture status on its own (AUC = 0.78). Different protocols to isolate the aneurysm dome did not affect the prediction performance. We identified problems regarding generalizability if trained models are applied to datasets with different selection biases.ConclusionsMorphology provided a clear indication of the aneurysm disease status, with parameters measuring shape (especially irregularity) being better predictors than size. Quantitative measurement of shape, alone or in conjunction with information about aneurysm location, has the potential to improve the clinical assessment of intracranial aneurysms.
Higher Genetically Predicted Triglycerides, LDL, and HDL Increase the Vitamin D Deficiency: A Mendelian Randomization Study
Authors: Lu Zhe , Jiao Yang , Li Jun 
Published: May 2022

IntroductionIt has been proven that high body mass index (BMI) levels can cause vitamin D deficiency, but the mechanism is still unclear. Therefore, this study attempts to explain this phenomenon from the perspective of blood lipid by using mendelian randomization (MR).MethodsGenome-wide association studies (GWAS) summary datasets for serum lipids were obtained from the Global Lipids Genetics Consortium (GLGC). Vitamin D deficiency outcome data were acquired from the UK Biobank samples. Single-variable MR (SVMR) and multi-variable MR (MVMR) analyses were conducted using the TwoSampleMR package based on R 4.0.3. The four main methods were the random-effect inverse-variance weighted (IVW), MR-Egger, weighted-median method, and weighted mode.ResultsIn the SVMR of serum lipid/apolipoprotein levels on serum vitamin D level, it was found that elevated serum triacylglycerol (IVW, OR = 0.85, 95%CI:0.81–0.89, P &lt; 0.001), low-density lipoprotein (LDL) (IVW, OR = 0.93, 95%CI:0.90–0.95, P &lt; 0.001), and high-density lipoprotein (HDL) (IVW, OR = 0.95, 95%CI:0.91–0.98, P &lt; 0.001) levels all had a causal relationship with vitamin D deficiency, but significant pleiotropy was detected in the triacylglycerol (P = 0.001) and HDL (P = 0.003) analysis. MVMR analysis results were consistent with SVMR.ConclusionBy using single-variable mendelian randomization and multi-variable mendelian randomization methods, we identified that the elevated serum triacylglycerol, LDL, and HDL levels all had a causal relationship with vitamin D deficiency. Taking into account the significant pleiotropy demonstrated in this study, the conclusions of this study should be treated with caution.
Prevalence of Helicobacter pylori in Non-Cardia Gastric Cancer in China: A Systematic Review and Meta-Analysis
Authors: Lu Yong , Xiao Fei , Wang Yuan , Wang Zhenyu , Liu Di , Hong Feng 
Published: May 2022

Non-cardia gastric cancer was significantly associated with Helicobacter pylori (H. pylori) infection. Reducing H. pylori prevalence was an important prevention strategy for non-cardia gastric cancer. However, national-level data on the H. pylori prevalence in non-cardia gastric cancer were limited in China. Therefore, we conducted this study to estimate the pooled prevalence of H. pylori in non-cardia gastric cancer in China. We searched PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang, and VIP Database for Chinese Technical Periodicals for studies reporting H. pylori prevalence in non-cardia gastric cancer in China which were published before September 1, 2021. Pooled prevalence was calculated using a random-effect model. Subgroup analysis and meta-regression were used to explore the potential sources of heterogeneity. Egger’s test and funnel plot were used to assess publication bias. A total number of 55 studies with 5324 cases of non-cardia gastric cancer were included in this study. The pooled prevalence of H. pylori in non-cardia gastric cancer in China was 66.5% (95%CI: 62%-71%, I2=93.8%, P&lt;0.0001). In subgroup analysis, a significant difference in the prevalence of H. pylori in non-cardia gastric cancer was noted when stratified by geographic region of China (P=0.0112). The highest H. pylori prevalence (78.9%, 95%CI: 69.9%-87.8%) was noted in Northwest China and the lowest (53.1%, 95%CI: 38.9%-67.3%) was in North China. In meta-regression, a significant association between H. pylori prevalence and geographic region was found, while type of sample, H. pylori testing method, diagnosis period, detection timing, type of study design, quality grade, publication year, and sample size were not associated with the prevalence of H. pylori in non-cardia gastric cancer (P&gt;0.05). A large proportion of non-cardia gastric cancers were associated with H. pylori infection in China, emphasizing the possible benefits of H. pylori eradication for the prevention and control of non-cardia gastric cancer.