bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating microbial cell–free DNA is increased during neutropenia after hematopoietic stem cell transplantation
Authors: Blair Lily M. , Akhund-Zade Jamilla , Katsamakis Zoe A. , Smibert Olivia C. , Wolfe Alex E. , Giardina Paul , Slingerland John , Bercovici Sivan , Perales Miguel-Angel , Taur Ying , van den Brink Marcel R. M. , Peled Jonathan U. , Markey Kate A. 
Published: July 2023

Abstract
We used a next-generation sequencing platform to characterize microbial cell–free DNA (mcfDNA) in plasma samples from patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT). In this observational study, we sought to characterize plasma mcfDNA in order to explore its potential association with the immunologic complications of transplantation. We compared serially collected patient samples with plasma collected from healthy control subjects. We observed changes in total mcfDNA burden in the plasma after transplantation, which was most striking during the early posttransplant neutropenic phase. This elevation could be attributed to a number of specific bacterial taxa, including Veillonella, Bacteroides, and Prevotella (genus level). For an additional cohort of patients, we compared the data of mcfDNA from plasma with 16s-ribosomal RNA sequencing data from stool samples collected at matched time points. In a number of patients, we confirmed that mcfDNA derived from specific microbial taxa (eg, Enterococcus) could also be observed in the matched stool sample. Quantification of mcfDNA may generate novel insights into mechanisms by which the intestinal microbiome influences systemic cell populations and, thus, has been associated with outcomes for patients with cancer.
Polygenic risk of major depressive disorder as a risk factor for venous thromboembolism
Authors: Ward Joey , Le Ngoc-Quynh , Suryakant Suryakant , Brody Jennifer A. , Amouyel Philippe , Boland Anne , Bown Rosemary , Cullen Breda , Debette Stéphanie , Deleuze Jean-François , Emmerich Joseph , Graham Nicholas , Germain Marine , Anderson Jana J. , Pell Jill P. , Lyall Donald M. , Lyall Laura M. , Smith Daniel J. , Wiggins Kerri L. , Soria José Manuel , Souto Juan Carlos , Morange Pierre-Emmanuel , Smith Nicholas L. , Trégouët David-Alexandre , Sabater-Lleal Maria , Strawbridge Rona J. 
Published: July 2023

Abstract
Major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ) are associated with an increased risk of cardiovascular diseases, including venous thromboembolism (VTE). The reasons for this are complex and include obesity, smoking, and use of hormones and psychotropic medications. Genetic studies have increasingly provided evidence of the shared genetic risk of psychiatric and cardiometabolic illnesses. This study aimed to determine whether a genetic predisposition to MDD, BD, or SCZ is associated with an increased risk of VTE. Genetic correlations using the largest genome-wide genetic meta-analyses summary statistics for MDD, BD, and SCZ (Psychiatric Genetics Consortium) and a recent genome-wide genetic meta-analysis of VTE (INVENT Consortium) demonstrated a positive association between VTE and MDD but not BD or SCZ. The same summary statistics were used to construct polygenic risk scores for MDD, BD, and SCZ in UK Biobank participants of self-reported White British ancestry. These were assessed for impact on self-reported VTE risk (10 786 cases, 285 124 controls), using logistic regression, in sex-specific and sex-combined analyses. We identified significant positive associations between polygenic risk for MDD and the risk of VTE in men, women, and sex-combined analyses, independent of the known risk factors. Secondary analyses demonstrated that this association was not driven by those with lifetime experience of mental illness. Meta-analyses of individual data from 6 additional independent cohorts replicated the sex-combined association. This report provides evidence for shared biological mechanisms leading to MDD and VTE and suggests that, in the absence of genetic data, a family history of MDD might be considered when assessing the risk of VTE.
Tanshinone I specifically suppresses NLRP3 inflammasome activation by disrupting the association of NLRP3 and ASC
Authors: Zhao Jia , Liu Hongbin , Hong Zhixian , Luo Wei , Mu Wenqing , Hou Xiaorong , Xu Guang , Fang Zhie , Ren Lutong , Liu Tingting , Wen Jincai , Shi Wei , Wei Ziying , Yang Yongping , Zou Wenjun , Zhao Jun , Xiao Xiaohe , Bai Zhaofang , Zhan Xiaoyan 
Published: July 2023

Abstract
Background
Abnormal activation of NLRP3 inflammasome is related to a series of inflammatory diseases, including type 2 diabetes, gouty arthritis, non-alcoholic steatohepatitis (NASH), and neurodegenerative disorders. Therefore, targeting NLRP3 inflammasome is regarded as a potential therapeutic strategy for many inflammatory diseases. A growing number of studies have identified tanshinone I (Tan I) as a potential anti-inflammatory agent because of its good anti-inflammatory activity. However, its specific anti-inflammatory mechanism and direct target are unclear and need further study.

Methods
IL-1β and caspase-1 were detected by immunoblotting and ELISA, and mtROS levels were measured by flow cytometry. Immunoprecipitation was used to explore the interaction between NLRP3, NEK7 and ASC. In a mouse model of LPS-induced septic shock, IL-1β levels in peritoneal lavage fluid and serum were measured by ELISA. Liver inflammation and fibrosis in the NASH model were analyzed by HE staining and immunohistochemistry.

Results
Tan I inhibited the activation of NLRP3 inflammasome in macrophages, but had no effect on the activation of AIM2 or NLRC4 inflammasome. Mechanistically, Tan I inhibited NLRP3 inflammasome assembly and activation by targeting NLRP3-ASC interaction. Furthermore, Tan I exhibited protective effects in mouse models of NLRP3 inflammasome-mediated diseases, including septic shock and NASH.

Conclusions
Tan I specifically suppresses NLRP3 inflammasome activation by disrupting the association of NLRP3 and ASC, and exhibits protective effects in mouse models of LPS-induced septic shock and NASH. These findings suggest that Tan I is a specific NLRP3 inhibitor and may be a promising candidate for treating NLRP3 inflammasome-related diseases.

Graphical Abstract
NNAT is a novel mediator of oxidative stress that suppresses ER + breast cancer
Authors: Plasterer Cody , Semenikhina Marharyta , Tsaih Shirng-Wern , Flister Michael J , Palygin Oleg 
Published: July 2023

Abstract
Background
Neuronatin (NNAT) was recently identified as a novel mediator of estrogen receptor-positive (ER+) breast cancer cell proliferation and migration, which correlated with decreased tumorigenic potential and prolonged patient survival. However, despite these observations, the molecular and pathophysiological role(s) of NNAT in ER + breast cancer remains unclear. Based on high protein homology with phospholamban, we hypothesized that NNAT mediates the homeostasis of intracellular calcium [Ca2+]i levels and endoplasmic reticulum (EndoR) function, which is frequently disrupted in ER + breast cancer and other malignancies.

Methods
To evaluate the role of NNAT on [Ca2+]i homeostasis, we used a combination of bioinformatics, gene expression and promoter activity assays, CRISPR gene manipulation, pharmacological tools and confocal imaging to characterize the association between ROS, NNAT and calcium signaling.

Results
Our data indicate that NNAT localizes predominantly to EndoR and lysosome, and genetic manipulation of NNAT levels demonstrated that NNAT modulates [Ca2+]i influx and maintains Ca2+ homeostasis. Pharmacological inhibition of calcium channels revealed that NNAT regulates [Ca2+]i levels in breast cancer cells through the interaction with ORAI but not the TRPC signaling cascade. Furthermore, NNAT is transcriptionally regulated by NRF1, PPARα, and PPARγ and is strongly upregulated by oxidative stress via the ROS and PPAR signaling cascades.

Conclusion
Collectively, these data suggest that NNAT expression is mediated by oxidative stress and acts as a regulator of Ca2+ homeostasis to impact ER + breast cancer proliferation, thus providing a molecular link between the longstanding observation that is accumulating ROS and altered Ca2+ signaling are key oncogenic drivers of cancer.
Single-cell RNA sequencing for the study of kidney disease
Authors: Zhu Jiayi , Lu Jinrong , Weng Huachun 
Published: July 2023

AbstractThe kidney is an important organ for maintaining normal metabolism and stabilising the internal environment, in which, the heterogeneity of cell types has hindered the progress in understanding the mechanisms underlying kidney disease. In recent years the application of single-cell RNA sequencing (scRNA-seq) in nephrology has developed rapidly. In this review, we summarized the technical platform related to scRNA-seq and the role of this technology in investigating the onset and development of kidney diseases, starting from several common kidney diseases (mainly including lupus nephritis, renal cell carcinoma, diabetic nephropathy and acute kidney injury), and provide a reference for the application of scRNA-seq in the study of kidney disease diagnosis, treatment and prognosis.
Associations and gastrointestinal symptoms in women with endometriosis in comparison to women with irritable bowel syndrome: a study based on a population cohort
Authors: Junkka Sofie Stark , Ohlsson Bodil 
Published: July 2023

Abstract
Background
Endometriosis and irritable bowel syndrome (IBS) have similar symptoms, pathogenesis, and risk factors. These diagnoses often coexist and are frequently misdiagnosed leading to diagnostic delays. This study of a population-based cohort aimed to investigate associations relating to endometriosis and IBS and to compare gastrointestinal symptoms between endometriosis and IBS.

Method
The study cohort included women from the Malmö Offspring Study with information about endometriosis and IBS diagnoses from the National Board of Health and Welfare. The participants answered a questionnaire about lifestyle habits, medical and drug history, and self-reported IBS. The visual analog scale for IBS was used to estimate gastrointestinal symptoms the past 2 weeks. Endometriosis diagnosis and self-reported IBS were used as dependent variables to study associations with age, body mass index (BMI), education, occupation, marital status, smoking, alcohol habits, and physical activity using logistic regression. Mann-Whitney U Test or Kruskal-Wallis tests were used to calculate the differences in symptoms between groups.

Results
Of the 2,200 women with information from medical records, 72 participants had endometriosis; 21 (29.2%) of these had self-reported IBS. Of the 1,915 participants who had answered the questionnaire, 436 (22.8%) had self-reported IBS. Endometriosis was associated with IBS (OR:1.86; 95%CI:1.06–3.26; p = 0.029), as well as with age 50–59 years (OR:6.92; 95%CI:1.97–24.32; p = 0.003), age ≥ 60 years (OR:6.27; 95%CI:1.56–25.17; p = 0.010), sick leave (OR:2.43; 95%CI:1.08–5.48; p = 0.033), and former smoking (OR:3.02; 95%CI:1.19–7.68; p = 0.020). There was an inverse association with BMI (OR:0.36; 95%CI:0.14–4.91; p = 0.031). IBS was associated with endometriosis (OR:1.77; 95%CI:1.02–3.07; p = 0.041) and sick leave (OR:1.77; 95%CI:1.14–2.73; p = 0.010), with a tendency to association with smoking (OR:1.30; 95%CI:0.98–1.72; p = 0.071). When excluding participants using drugs associated with IBS, the condition was associated with current smoking (OR:1.39; 95%CI:1.03–1.89; p = 0.033) and inversely with age 50–59 years (OR:0.58; 95%CI:0.38–0.90; p = 0.015). There were differences in the gastrointestinal symptoms between IBS and healthy participants, but not between endometriosis and IBS or healthy participants.

Conclusion
There were associations between endometriosis and IBS, without differences in gastrointestinal symptoms. Both IBS and endometriosis were associated with smoking and sick leave. Whether the associations reflect causality or depend on common risk factors and pathogenesis remains to be determined.
Optimized screening of DNA methylation sites combined with gene expression analysis to identify diagnostic markers of colorectal cancer
Authors: Ye Zhen , Song Guangle , Liang Jianwei , Yi Shuying , Gao Yuqi , Jiang Hanming 
Published: July 2023

Abstract
Background
The prognosis of patients with colorectal cancer is related to early detection. However, commonly used screening markers lack sensitivity and specificity. In this study, we identified diagnostic methylation sites for colorectal cancer.

Methods
After screening the colorectal cancer methylation dataset, diagnostic sites were identified via survival analysis, difference analysis, and ridge regression dimensionality reduction. The correlation between the selected methylation sites and the estimation of immune cell infiltration was analyzed. The accuracy of the diagnosis was verified using different datasets and the 10-fold crossover method.

Results
According to Gene Ontology, the main enrichment pathways of genes with hypermethylation sites are axon development, axonogenesis, and pattern specification processes. However, the Kyoto Encyclopedia of Genes and Genomes (KEGG) suggests the following main enrichment pathways: neuroactive ligand–receptor interaction, calcium signaling, and cAMP signaling. In The Cancer Genome Atlas (TCGA) and GSE131013 datasets, the area under the curve of cg07628404 was > 0.95. For the NaiveBayes machine model of cg02604524, cg07628404, and cg27364741, the accuracies of 10-fold cross-validation in the GSE131013 and TCGA datasets were 95% and 99.4%, respectively. The survival prognosis of the hypomethylated group (cg02604524, cg07628404, and cg27364741) was better than that of the hypermethylated group. The mutation risk did not differ between the hypermethylated and hypomethylated groups. The correlation coefficient between the three loci and CD4 central memory T cells, hematological stem cells, and other immune cells was not high (p < 0.05).

Conclusion
In cases of colorectal cancer, the main enrichment pathway of genes with hypermethylated sites was axon and nerve development. In the biopsy tissues, the hypermethylation sites were diagnostic for colorectal cancer, and the NaiveBayes machine model of the three loci showed good diagnostic performance. Site (cg02604524, cg07628404, and cg27364741) hypermethylation predicts poor survival for colorectal cancer. Three methylation sites were weakly correlated with individual immune cell infiltration. Hypermethylation sites may be a useful repository for diagnosing colorectal cancer.
RETRACTED ARTICLE: Upregulation of
hsa_circ_0002003 promotes hepatocellular carcinoma progression
Authors: Zhou Lisha , Wang Qianwen , Hou Jun , Wu Xiangwei , Wang Lianghai , Chen Xueling 
Published: July 2023

Abstract
Background
Circular RNAs (circRNAs), which are involved in various human
malignancies, have emerged as promising biomarkers. The present study aimed to
investigate unique expression profiles of circRNAs in hepatocellular carcinoma
(HCC) and identify novel biomarkers associated with HCC development and
progression.

Methods
CircRNA expression profiles of HCC tissues were jointly analyzed to
identify differentially expressed circRNAs. Overexpression plasmid and siRNA
targeting candidate circRNAs were used in functional assays in vitro.
CircRNA-miRNA interactions were predicted using miRNAs expressed in the
miRNA-seq dataset GSE76903. To further screen downstream genes targeted by the
miRNAs, survival analysis and qRT-PCR were conducted to evaluate their
prognostic role in HCC and construct a ceRNA regulatory network.

Results
Three significantly upregulated circRNAs, hsa_circ_0002003,
hsa_circ_0002454, and hsa_circ_0001394, and one significantly downregulated
circRNA, hsa_circ_0003239, were identified and validated by qRT-PCR. Our in
vitro data indicated that upregulation of hsa_circ_0002003 accelerated cell
growth and metastasis. Mechanistically, DTYMK, DAP3, and STMN1, which were targeted by hsa-miR-1343-3p, were
significantly downregulated in HCC cells when hsa_circ_0002003 was silenced and
were significantly correlated with poor prognosis in patients with HCC.

Conclusion
Hsa_circ_0002003 may play critical roles in HCC pathogenesis and
serve as a potential prognostic biomarker for HCC. Targeting the
hsa_circ_0002003/hsa-miR-1343-3p/STMN1 regulatory axis could be an effective
therapeutic strategy in patients with HCC.
The role of heavy metals in the development of colorectal cancer
Authors: Li Yongsheng , Lou Jingwei , Hong Shaozhong , Hou Dengfeng , Lv Yandong , Guo Zhiqiang , Wang Kai , Xu Yue , Zhai Yufeng , Liu Hongzhou 
Published: July 2023

Abstract
Objective
To investigate the relationship among 18 heavy metals, microsatellite instability (MSI) status, ERCC1, XRCC1 (rs25487), BRAF V600E and 5 tumor markers and their role in the development of colorectal cancer (CRC).

Methods
A total of 101 CRC patients and 60 healthy controls were recruited in the present study. The levels of 18 heavy metals were measured by ICP-MS. MSI status and the genetic polymorphism were determined by PCR (FP205-02, Tiangen Biochemical Technology Co., Ltd., Beijing, China) and Sanger sequencing. Spearman’s rank correlation was used to analyze the relationship among various factors.

Results
The level of selenium (Se) was lower in the CRC group compared with the control group (p < 0.01), while vanadium (V), arsenic (As), tin (Sn), barium (Ba) and lead (Pb) were higher (p < 0.05), chromium (Cr) and copper (Cu) were significantly higher (p < 0.0001) in the CRC group than those in the control group. Multivariate logistic regression analysis indicated that Cr, Cu, As and Ba were the risk factors for CRC. In addition, CRC was positively correlated with V, Cr, Cu, As, Sn, Ba and Pb, but negatively correlated with Se. MSI was positively correlated with BRAF V600E, but negatively correlated with ERCC1. BRAF V600E was positively correlated with antimony (Sb), thallium (Tl), CA19-9, NSE, AFP and CK19. XRCC1 (rs25487) was found to be positively correlated with Se but negatively correlated with Co. The levels of Sb and Tl were significantly higher in the BRAF V600E positive group compared to the negative group. The mRNA expression level of ERCC1 was significantly higher (P = 0.035) in MSS compared to MSI. And there was a significant correlation between XRCC1 (rs25487) polymorphism and MSI status (P<0.05).

Conclusion
The results showed that low level of Se and high levels of V, As, Sn, Ba, Pb, Cr, and Cu increased the risk of CRC. Sb and Tl may cause BRAF V600E mutations, leading to MSI. XRCC1 (rs25487) was positively correlated with Se but negatively correlated with Co. The expression of ERCC1 may be related to MSS, while the XRCC1 (rs25487) polymorphism is related to MSI.
Unhealthy lifestyles and clusters status among 3637 adolescents aged 11–23 years: a school-based cross-sectional study in China
Authors: Song Yalin , Liu Jingru , Zhao Yize , Gong Lu , Chen Qiuyuan , Jiang Xili , Zhang Jiangtao , Hao Yudan , Zhou Huijun , Lou Xiaomin , Wang Xian 
Published: July 2023

Abstract
Background
Unhealthy lifestyles are risk factors for non-communicable diseases (NCDs) and tend to be clustered, with a trajectory that extends from adolescence to adulthood. This study investigated the association of diets, tobacco, alcohol, physical activity (PA), screen time (ST) and sleep duration (SD) in a total of six lifestyles, separately and as cumulative lifestyle scores, with sociodemographic characteristics among school-aged adolescents in the Chinese city of Zhengzhou.

Methods
In the aggregate, 3,637 adolescents aged 11–23 years were included in the study. The questionnaire collected data on socio-demographic characteristics and lifestyles. Healthy and unhealthy lifestyles were identified and scored, depending on the individual score (0 and 1 for healthy and unhealthy lifestyles respectively), with a total score between 0 and 6. Based on the sum of the dichotomous scores, the number of unhealthy lifestyles was calculated and divided into three clusters (0–1, 2–3, 4–6). Chi-square test was used to analyze the group difference of lifestyles and demographic characteristics, and multivariate logistic regression was used to explore the associations between demographic characteristics and the clustering status of unhealthy lifestyles.

Results
Among all participants, the prevalence of unhealthy lifestyles was: 86.4% for diet, 14.5% for alcohol, 6.0% for tobacco, 72.2% for PA, 42.3% for ST and 63.9% for SD. Students who were in university, female, lived in country (OR = 1.725, 95% CI: 1.241–2.398), had low number of close friends (1–2: OR = 2.110, 95% CI: 1.428–3.117; 3–5: OR = 1.601, 95% CI: 1.168–2.195), and had moderate family income (OR = 1.771, 95% CI: 1.208–2.596) were more likely to develop unhealthy lifestyles. In total, unhealthy lifestyles remain highly prevalent among Chinese adolescents.

Conclusion
In the future, the establishment of an effective public health policy may improve the lifestyle profile of adolescents. Based on the lifestyle characteristics of different populations reported in our findings, lifestyle optimization can be more efficiently integrated into the daily lives of adolescents. Moreover, it is essential to conduct well-designed prospective studies on adolescents.
Association between night shift work and NAFLD: a prospective analysis of 281,280 UK Biobank participants
Authors: Huang Hangkai , Liu Zhening , Xie Jiarong , Xu Chengfu 
Published: July 2023

AbstractContextThis study aimed to investigate the association between night shift work and the risk of nonalcoholic fatty liver disease (NAFLD).MethodsWe conducted a prospective analysis of 281,280 UK Biobank participants. Cox proportional hazards models were used to estimate the association of night shift work with incident NAFLD. Polygenic risk score analyses were performed to assess whether a genetic predisposition to NAFLD modified the association.ResultsDuring a median follow-up of 12.1 years (3,373,964 person-years), 2,555 incident NAFLD cases were identified. Compared with workers who never/rarely worked night shifts, those who worked some night shifts or usual/permanent night shifts were 1.12 (95% CI: 0.96–1.31) and 1.27 (95% CI: 1.08–1.48) times more likely to develop NAFLD, respectively. Among the 75,059 participants who had reports on lifetime experience of night shift work, those with a longer duration, a higher frequency, more consecutive night shifts and a longer length per shift all showed higher risks of incident NAFLD. Further analyses showed that the association between night shift work and incident NAFLD was not modified by a genetic predisposition to NAFLD.ConclusionsNight shift work was associated with increased risks of incident NAFLD.