bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between circulating leukocytes and arrhythmias: Mendelian randomization analysis in immuno-cardiac electrophysiology
Authors: Chen Yuxiao , Lou Lian , Zhang Xuan , Jin Luyang , Chen Yao , Chen Lele , Li Zhihang , Zhang Fen , Fu Ting , Hu Shenjiang , Yang Jian 
Published: April 2023

BackgroundCardiac arrhythmia is a common disease associated with high mortality and morbidity. Circulating leukocyte counts, which serve as a biomarker for assessing systemic immune status, have been linked to arrhythmias in observational studies. However, observational studies are plagued by confounding factors and reverse causality, whether alterations in circulating leukocyte components are causally associated with arrhythmias remains uncertain. The present study explored this question based on genetic evidence.Methods and findingsWe performed Mendelian randomization (MR) analysis to evaluate whether alterations in leukocyte counts affect aggregated risk of all types of arrhythmia or risk of five specific types of arrhythmia. Single-nucleotide polymorphisms serving as proxies for leukocyte differential counts were retrieved from the Blood Cell Consortium, and statistical data on arrhythmias were obtained from the UK Biobank), FinnGenand a meta-analysis of genome-wide association studies for atrial fibrillation. We applied inverse variance-weighted method as the primary analysis, complemented by a series of sensitivity analyses. Bidirectional analyses were conducted to assess reverse causality. Finally, multivariable MR was performed to study the joint effects of multiple risk factors. We found that genetically predicted differential leukocyte counts were not significantly associated with aggregated occurrence of all types of arrhythmia. In contrast, each 1-standard deviation increase in lymphocyte count was associated with 46% higher risk of atrioventricular block (OR 1.46, 95% CI 1.11–1.93, p=0.0065). A similar effect size was observed across all MR sensitivity analyses, with no evidence of horizontal pleiotropy. Reverse MR analysis suggested that atrioventricular block was unlikely to cause changes in lymphocyte count. Primary MR analysis based on the inverse-variance weighted method suggested that changes in neutrophil count alter risk of right bundle branch block, and changes in basophil count alter risk of atrial fibrillation. However, these causal relationships were not robust in sensitivity analyses. We found no compelling evidence that neutrophil or lymphocyte counts cause atrial fibrillation.ConclusionOur data support higher lymphocyte count as a causal risk factor for atrioventricular block. These results highlight the importance of immune cells in the pathogenesis of specific cardiac conduction disorders.
The retrospective study of the metabolic patterns of BCG-vaccination in type-2 diabetic individuals in COVID-19 infection
Authors: Anwardeen Najeha R. , Cyprian Farhan S. , Yassine Hadi M. , Al-Thani Asmaa A. , Abdallah Abdallah M. , Emara Mohamed M. , Elrayess Mohamed A. 
Published: April 2023

BackgroundThe cross-protective nature of Bacillus Calmette-Guerin (BCG) vaccine against SARS-CoV-2 virus was previously suggested, however its effect in COVID-19 patients with type 2 diabetes (T2D) and the underlying metabolic pathways has not been addressed. This study aims to investigate the difference in the metabolomic patterns of type 2 diabetic patients with BCG vaccination showing different severity levels of COVID-19 infection.MethodsSixty-seven COVID-19 patients were categorized into diabetic and non-diabetic individuals who had been previously vaccinated or not with BCG vaccination. Targeted metabolomics were performed from serum samples from all patients using tandem mass spectrometry. Statistical analysis included multivariate and univariate models.ResultsData suggested that while BCG vaccination may provide protection for individuals who do not have diabetes, it appears to be linked to more severe COVID-19 symptoms in T2D patients (p = 0.02). Comparing the metabolic signature of BCG vaccinated T2D individuals to non-vaccinated counterparts revealed that amino acid (sarcosine), cholesterol esters (CE 20:0, 20:1, 22:2), carboxylic acid (Aconitic acid) were enriched in BCG vaccinated T2D patients, whereas spermidine, glycosylceramides (Hex3Cer(d18:1_22:0), Hex2Cer(d18:1/22:0), HexCer(d18:1/26:1), Hex2Cer(d18:1/24:0), HexCer(d18:1/22:0) were higher in BCG vaccinated non- T2D patients. Furthermore, data indicated a decrease in sarcosine synthesis from glycine and choline and increase in spermidine synthesis in the BCG vaccinated cohort in T2D and non-T2D groups, respectively.ConclusionThis pilot study suggests increased severity of COVID-19 in BCG vaccinated T2D patients, which was marked by decreased sarcosine synthesis, perhaps via lower sarcosine-mediated removal of viral antigens.
Anoikis resistance of small airway epithelium is involved in the progression of chronic obstructive pulmonary disease
Authors: Chen Dian , Yi Rongbing , Hong Weifeng , Wang Kai , Chen Yahong 
Published: April 2023

BackgroundAnoikis resistance is recognized as a crucial step in the metastasis of cancer cells. Most epithelial tumors are distinguished by the ability of epithelial cells to abscond anoikis when detached from the extracellular matrix. However, no study has investigated the involvement of anoikis in the small airway epithelium (SAE) of chronic obstructive pulmonary disease (COPD).MethodsAnoikis-related genes (ANRGs) exhibiting differential expression in COPD were identified using microarray datasets obtained from the Gene Expression Omnibus (GEO) database. Unsupervised clustering was performed to classify COPD patients into anoikis-related subtypes. Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, gene set enrichment analysis (GSEA), and gene set variation analysis (GSVA) were used to annotate the functions between different subtypes. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were leveraged to identify key molecules. The relative proportion of infiltrating immune cells in the SAE was quantified using the CIBERSORT and ssGSEA computational algorithms, and the correlation between key molecules and immune cell abundance was analyzed. The expression of key molecules in BEAS-2B cells exposed to cigarette smoke extract (CSE) was validated using qRT-PCR.ResultsA total of 25 ANRGs exhibited differential expression in the SAE of COPD patients, based on which two subtypes of COPD patients with distinct anoikis patterns were identified. COPD patients with anoikis resistance had more advanced GOLD stages and cigarette consumption. Functional annotations revealed a different immune status between COPD patients with pro-anoikis and anoikis resistance. Tenomodulin (TNMD) and long intergenic non-protein coding RNA 656 (LINC00656) were subsequently identified as key molecules involved in this process, and a close correlation between TNMD and the infiltrating immune cells was observed, such as activated CD4+ memory T cells, M1 macrophages, and activated NK cells. Further enrichment analyses clarified the relationship between TNMD and the inflammatory and apoptotic signaling pathway as the potential mechanism for regulating anoikis. In vitro experiments showed a dramatic upregulation of TNMD and LINC00656 in BEAS-2B cells when exposed to 3% CSE for 48 hours.ConclusionTNMD contributes to the progression of COPD by inducing anoikis resistance in SAE, which is intimately associated with the immune microenvironment.
Machine learning-based integration develops an immune-related risk model for predicting prognosis of high-grade serous ovarian cancer and providing therapeutic strategies
Authors: Wu Qihui , Tian Ruotong , He Xiaoyun , Liu Jiaxin , Ou Chunlin , Li Yimin , Fu Xiaodan 
Published: April 2023

BackgroundHigh-grade serous ovarian cancer (HGSOC) is a highly lethal gynecological cancer that requires accurate prognostic models and personalized treatment strategies. The tumor microenvironment (TME) is crucial for disease progression and treatment. Machine learning-based integration is a powerful tool for identifying predictive biomarkers and developing prognostic models. Hence, an immune-related risk model developed using machine learning-based integration could improve prognostic prediction and guide personalized treatment for HGSOC.MethodsDuring the bioinformatic study in HGSOC, we performed (i) consensus clustering to identify immune subtypes based on signatures of immune and stromal cells, (ii) differentially expressed genes and univariate Cox regression analysis to derive TME- and prognosis-related genes, (iii) machine learning-based procedures constructed by ten independent machine learning algorithms to screen and construct a TME-related risk score (TMErisk), and (iv) evaluation of the effect of TMErisk on the deconstruction of TME, indication of genomic instability, and guidance of immunotherapy and chemotherapy.ResultsWe identified two different immune microenvironment phenotypes and a robust and clinically practicable prognostic scoring system. TMErisk demonstrated superior performance over most clinical features and other published signatures in predicting HGSOC prognosis across cohorts. The low TMErisk group with a notably favorable prognosis was characterized by BRCA1 mutation, activation of immunity, and a better immune response. Conversely, the high TMErisk group was significantly associated with C-X-C motif chemokine ligands deletion and carcinogenic activation pathways. Additionally, low TMErisk group patients were more responsive to eleven candidate agents.ConclusionOur study developed a novel immune-related risk model that predicts the prognosis of ovarian cancer patients using machine learning-based integration. Additionally, the study not only depicts the diversity of cell components in the TME of HGSOC but also guides the development of potential therapeutic techniques for addressing tumor immunosuppression and enhancing the response to cancer therapy.
Strength variation characteristics of waste tailings cemented backfill materials with ultrafine particles
Authors: Deng Daiqiang , Wang Ye , Liang Yihua , Fan Jinkuan , Gao Yu , Ma Yunfan 
Published: April 2023

This study investigates the use of self-produced solid waste in mines to backfill the goaf, with energy saving and emission reduction technology requirements. Using a relevant backfill mixing proportion test and mechanical property test, we analyzed the strength variation law of backfill materials under different concentrations and cementation powder addition. The results showed that, for backfill materials at 7 days with an ash-tailings ratio of 1:6, the strength of specimens with 52% and 49% prepared concentrations, respectively, increased by 1.361 and 1.266 times over specimens with 49% and 46% concentrations. For backfill materials with 49% prepared concentrations and ash-tailings ratios of 1:6, 1:9, and 1:12, the specimen strength of the backfill materials with ratios of 1:6 and 1:9 improved by 0.616 MPa and 0.321 MPa—109.28% and 114.6%, respectively—compared with 1:9 and 1:12 backfill materials at 60 days. It is thus evident that the quantity of binding materials added plays a critical function in improving the strength of backfill materials, and in the subsequent application of goaf backfill. The strength of backfill materials can be enhanced by improving the gradation of backfill aggregates and increasing the amount of binding materials so as to achieve cost reductions and sustainable development.
A feasibility study for quantitative assessment of cerebrovascular malformations using flutriciclamide ([18F]GE-180) PET/MRI
Authors: Kim Sally Ji Who , Lupo Janine M. , Chen Yicheng , Pampaloni Miguel H. , VanBrocklin Henry F. , Narvid Jared , Kim Helen , Seo Youngho 
Published: April 2023

AimNeuroinflammation plays a key role in both the pathogenesis and the progression of cerebral cavernous malformations (CCM). Flutriciclamide ([18F]GE-180) is a translocator protein (TSPO) targeting positron emission tomography (PET) tracer, developed for imaging neuroinflammation. The objectives of this study were to describe characteristics of flutriciclamide uptake in different brain tissue regions in CCM patients compared to controls, and to evaluate flutriciclamide uptake and iron deposition within CCM lesions.Materials and methodsFive patients with CCM and six controls underwent a 60 or 90 min continuous PET/MRI scan following 315 ± 68.9 MBq flutriciclamide administration. Standardized uptake value (SUV) and standardized uptake value ratio (SUVr) were obtained using the striatum as a pseudo-reference. Quantitative susceptibility maps (QSM) were used to define the location of the vascular malformation and calculate the amount of iron deposition in each lesion.ResultsIncreased flutriciclamide uptake was observed in all CCM lesions. The temporal pole demonstrated the highest radiotracer uptake; the paracentral lobule, cuneus and hippocampus exhibited moderate uptake; while the striatum had the lowest uptake, with average SUVs of 0.66, 0.55, 0.63, 0.55, and 0.33 for patient with CCM and 0.57, 0.50, 0.48, 0.42, and 0.32 for controls, respectively. Regional SUVr showed similar trends. The average SUV and QSM values in CCM lesions were 0.58 ± 0.23 g/ml and 0.30 ± 0.10 ppm. SUVs and QSM were positively correlated in CCM lesions (r = 0.53, p = 0.03).ConclusionThe distribution of flutriciclamide ([18F]GE-180) in the human brain and CCM lesions demonstrated the potential of this TSPO PET tracer as a marker of neuroinflammation that may be relevant for characterizing CCM disease progression along with QSM.
Dual-task gait and white matter hyperintensities in Lewy body diseases: An exploratory analysis
Authors: Fatokun Ipinuoluwakiye , Gee Myrlene , Nelles Krista , Ba Fang , Dadar Mahsa , Duchesne Simon , Sharma Breni , Masellis Mario , Black Sandra E. , Almeida Quincy J. , Smith Eric E. , Pieruccini-Faria Frederico , Montero-Odasso Manuel , Camicioli Richard 
Published: April 2023

BackgroundParkinson’s disease (PD) and dementia with Lewy bodies (DLB) are part of a spectrum of Lewy body disorders, who exhibit a range of cognitive and gait impairments. Cognitive-motor interactions can be examined by performing a cognitive task while walking and quantified by a dual task cost (DTC). White matter hyperintensities (WMH) on magnetic resonance imaging have also been associated with both gait and cognition. Our goal was to examine the relationship between DTC and WMH in the Lewy body spectrum, hypothesizing DTC would be associated with increased WMH volume.MethodsSeventy-eight participants with PD, PD with mild cognitive impairment (PD-MCI), PD with dementia or DLB (PDD/DLB), and 20 cognitively unimpaired participants were examined in a multi-site study. Gait was measured on an electronic walkway during usual gait, counting backward, animal fluency, and subtracting sevens. WMH were quantified from magnetic resonance imaging using an automated pipeline and visual rating. A median split based on DTC was performed. Models included age as well as measures of global cognition and cardiovascular risk.ResultsCompared to cognitively unimpaired participants, usual gait speed was lower and DTC was higher in PD-MCI and PDD/DLB. Low DTC participants had higher usual gait speed. WMH burden was greater in high counting DTC participants. Frontal WMH burden remained significant after adjusting for age, cardiovascular risk and global cognition.ConclusionIncreased DTC was associated with higher frontal WMH burden in Lewy body disorders after adjusting for age, cardiovascular risk, and global cognition. Higher DTC was associated with age.
Electroacupuncture treatment ameliorates depressive-like behavior and cognitive dysfunction via CB1R dependent mitochondria biogenesis after experimental global cerebral ischemic stroke
Authors: Hu Guangtao , Zhou Cuihong , Wang Jin , Ma Xinxu , Ma Hongzhe , Yu Huan , Peng Zhengwu , Huang Jing , Cai Min 
Published: April 2023

IntroductionThis study aimed to identify the effect of electroacupuncture (EA) treatment on post-stroke depression (PSD) and explore whether cannabinoid receptor 1 (CB1R)-mediated mitochondrial biogenesis accounts for the treatment effect of EA.MethodsThe PSD mouse model was induced by a consecutive 14-day chronic unpredictable stress operation after 7 days of recovery from the bilateral common carotid artery occlusion surgery. Either EA treatment or sham stimulation was performed for 14 consecutive days from Day 7 after the BCCAO operation. Subjects’ PSD-like behaviors were tested via open field test, sucrose preference test, novelty suppressed feeding test, tail suspension test, and forced swim test, and subjects’ cognitive function was examined using Y-maze and novelty object recognition test. In addition, the levels of CB1R, mitochondrial biogenesis-related proteins (nuclear transcription factor 1, NRF1; mitochondrial transcription factor A, TFAM), proteins related to mitochondrial function (Cytochrome C, Cyto C; AIF, COX IV), and mitochondrial DNA were measured. To elucidate the role of CB1R in EA treatment, CB1R antagonists AM251 and CB1R-shRNA were given to mice before EA treatment. Likewise, subjects’ depressive-like behaviors, cognitive function, mitochondrial function, and mitochondrial biogenesis were examined after the PSD procedure.ResultsIt has been showed that EA successfully ameliorated depressive-like behaviors, improved cognitive dysfunctions, and upregulated CB1R, NRF1 and TFAM expressions. However, the supplementation of AM251 and CB1R-shRNA blocked the antidepressant-like effects generated by EA, and EA failed to improve cognitive dysfunction, upregulate CB1R protein expression, and increase mitochondrial function and biogenesis.ConclusionAltogether, these results indicated that EA ameliorated PSD-like behaviors in mice, improved cognitive dysfunctions after PSD, and promoted mitochondrial biogenesis by activating CB1R, a novel mechanism underlying EA’s antidepressant-like effects in treating PSD.
An fMRI analysis of verbal and non-verbal working memory in people with a past history of opioid dependence
Authors: Berenbaum Joshua G. , Nadkarni Prianca A. , Marvel Cherie L. 
Published: April 2023

IntroductionWorking memory describes the ability to maintain and manipulate information held in mind, and it is a fundamental aspect of executive function. Within drug addiction, impairments of executive control over behavior are thought to lead to poor decision making and risky behaviors. Previous research has demonstrated working memory (WM) and executive function difficulties in opioid-dependent individuals, but the neural underpinnings of such impairments in this population are not well understood.MethodsThis study used functional magnetic resonance imaging to examine the neural mechanisms involved in WM in 13 opioid-dependent, methadone-maintained participants (OP) and 13 matched, healthy controls (HC). A Sternberg item-recognition task was administered with three conditions: (1) a “verbal” condition in which participants determined whether any six visually presented target letters matched a probe item that was presented 4–6 s later, (2) a “non-verbal” condition in which participants were presented with a Chinese character and, following a 4–6 s delay, determined whether the character matched the probe item, and (3) a “control” condition in which participants were presented with three horizontal lines and following the same delay, determined whether the lines matched a probe item (always the same three lines). Functional magnetic resonance imaging (fMRI) contrasts focused on the delay (or “maintenance”) phase for verbal and non-verbal conditions relative to the control condition.ResultsAccuracy on the WM task did not differ between groups, but the OP group was significantly slower to respond. The fMRI imaging results indicated differences in brain activity between the OP and HC groups. fMRI-guided regions of interest correlated with age of first alcohol and THC use, suggesting that early substance use, in addition to years of opioid-abuse, may have played a role in the OP group’s WM performance.DiscussionA deeper understanding of these neural differences between opioid-dependent individuals and their healthy control counterparts helps shed light on fundamental ways in which substance use impacts the brain and cognition, potentially opening up novel avenues for therapeutic targets to treat substance use disorder.
Association between dietary intake of anthocyanidins and heart failure among American adults: NHANES (2007–2010 and 2017–2018)
Authors: Tao Zaixiao , Zhang Rui , Zuo Wenjie , Ji Zhenjun , Fan Zhongguo , Chen Xi , Huang Rong , Li Xinxin , Ma Genshan 
Published: April 2023

BackgroundDespite anthocyanidins have anti-inflammatory and antioxidant properties, no studies have researched association between dietary intake of anthocyanidins and heart failure.MethodsWe enrolled 15,869 participants from the National Health and Nutrition Examination Survey (NHANES) (2007–2010 and 2017–2018) in this cross-sectional study. We examined baseline data and prevalence of heart failure in different quartile groups of anthocyanin intake (Q1-4). Three models were established through logistic regression to evaluate the protective effect of Q4 (highest anthocyanidins intake) on heart failure. The protective effect of high anthocyanidins intake on heart failure was further evaluated in different subgroups.ResultsParticipants with the highest anthocyanidins intake (Q4) had the lowest prevalence of heart failure (Q1:2.54%, Q2:2.33%, Q3:2.43%, Q4:1.57%, p = 0.02). After adjusting for possible confounding factors, compared with the Q1 group, the highest anthocyanidins intake (Q4) was independently related to lower presence of heart failure (Q4: OR 0.469, 95%CI [0.289, 0.732], p = 0.003). And this association was still stable in subgroups of female, ≥45 years, smoker, non-Hispanic White or without diabetes, stroke and renal failure.ConclusionDietary intake of anthocyanidins had negative association with the presence of heart failure.
Diagnostic value of superb microvascular imaging and color doppler for thyroid nodules: A meta-analysis
Authors: Luo Haorou , Yin Lixue 
Published: April 2023

ObjectiveSuperb micro-vascular imaging (SMI) is a new noninvasive modality for the diagnosis of thyroid nodules. However, the performance of SMI in differentiating malignant and benign thyroid nodules has not been systematically evaluated. This meta-analysis was performed to assess the accuracy of SMI in diagnosing thyroid nodules.MethodsPubMed, Cochrane Library, Embase, Web of Science, Sinomed, Scopus were searched. We recorded the characteristics of the included studies and assessed the quality of each study using the QUADAS-2 tool. The pooled sensitivity, specificity, positive likelihood ratio (LR), negative LR, diagnostic odds ratio (DOR), and area under the curve (AUC) were calculated. We also evaluated the publication bias.ResultsThis meta-analysis included 10 studies with a total of 1083 thyroid nodules. The pooled the sensitivity, specificity, and positive and negative LR were 0.84, 0.86, 6.2, and 0.18, respectively. The DOR and AUC were 33 and 0.91, respectively. Heterogeneity existed between the included studies. No significant publication bias was observed.ConclusionCompared with CDFI, Superb micro-vascular imaging (SMI) has higher diagnostic sensitivity and specificity, better diagnostic efficiency, and could be used to diagnose benign and malignant nodules in the display of blood flow distribution capabilities of thyroid nodules; at the same time, Fagan plot showed that the SMI technique had a good clinical application value, and it could supplement the deficiencies of color Doppler imaging in the diagnosis of thyroid nodules.