bluuebunny/crossref_metadata_2025_split huggingface dataset:
Projected heatwaves in Xinjiang Uygur autonomous region, China
Authors: Dong Diwen , Tao Hui , Zhang Zengxin , Mondal Sanjit Kumar 
Published: February 2024

Introduction: Heatwaves (HWs) are the serious natural disaster that exert great impacts on human health and social economy. Projecting future changes in HWs is crucial for the development of effective adaptation strategies.Method: This study investigates the variations of HWs in Xinjiang for three time periods (near-term, mid-term, and long-term) under four Shared Socioeconomic Pathways (SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5) using multi-model ensemble (MME). To enhance confidence in HWs projection, we evaluate the performance of 17 climate models in simulating HWs in terms of interannual variability and spatial patterns using interannual variability skill score (IVS) and distance between indices of simulation and observation (DISO), respectively, and generate MME using the overall performance.Results: Compared to the observed data, the overall performance of MME outperforms most of individual models, although many models effectively capture the characteristics of HWs. Projections indicate that HWs in Xinjiang will become more longer lasting and severe. Specifically, heatwave frequency (HWF) and heatwave duration (HWD) are projected to reach 7.5 times and 61 days, respectively, in the long-term under the SSP5-8.5 scenario. The spatial distribution of HWs exhibits significant heterogeneity, with high value regions primarily distributed in eastern Xinjiang and the eastern part of southern Xinjiang. Although the HWs area is projected to expand under all scenarios, the spatial pattern is anticipated to remain largely unchanged.Conclusion: These findings provide a comprehensive assessment of future variations in HWs, which are necessary for improving regional adaptive capacity to extreme heat risk.
Identification of important modules and biomarkers in diabetic cardiomyopathy based on WGCNA and LASSO analysis
Authors: Cui Min , Wu Hao , An Yajuan , Liu Yue , Wei Liping , Qi Xin 
Published: February 2024

BackgroundDiabetic cardiomyopathy (DCM) lacks specific and sensitive biomarkers, and its diagnosis remains a challenge. Therefore, there is an urgent need to develop useful biomarkers to help diagnose and evaluate the prognosis of DCM. This study aims to find specific diagnostic markers for diabetic cardiomyopathy.MethodsTwo datasets (GSE106180 and GSE161827) from the GEO database were integrated to identify differentially expressed genes (DEGs) between control and type 2 diabetic cardiomyopathy. We assessed the infiltration of immune cells and used weighted coexpression network analysis (WGCNA) to construct the gene coexpression network. Then we performed a clustering analysis. Finally, a diagnostic model was built by the least absolute shrinkage and selection operator (LASSO).ResultsA total of 3066 DEGs in the GSE106180 and GSE161827 datasets. There were differences in immune cell infiltration. According to gene significance (GS) &gt; 0.2 and module membership (MM) &gt; 0.8, 41 yellow Module genes and 1474 turquoise Module genes were selected. Hub genes were mainly related to the “proteasomal protein catabolic process”, “mitochondrial matrix” and “protein processing in endoplasmic reticulum” pathways. LASSO was used to construct a diagnostic model composed of OXCT1, CACNA2D2, BCL7B, EGLN3, GABARAP, and ACADSB and verified it in the GSE163060 and GSE175988 datasets with AUCs of 0.9333 (95% CI: 0.7801-1) and 0.96 (95% CI: 0.8861-1), respectively. H9C2 cells were verified, and the results were similar to the bioinformatics analysis.ConclusionWe constructed a diagnostic model of DCM, and OXCT1, CACNA2D2, BCL7B, EGLN3, GABARAP, and ACADSB were potential biomarkers, which may provide new insights for improving the ability of early diagnosis and treatment of diabetic cardiomyopathy.
Exploring the molecular mechanism of Xuebifang in the treatment of diabetic peripheral neuropathy based on bioinformatics and network pharmacology
Authors: Hu Faquan , Lin Jiaran , Xiong Liyuan , Li Zhengpin , Liu Wen-ke , Zheng Yu-jiao 
Published: February 2024

BackgroundXuebifang (XBF), a potent Chinese herbal formula, has been employed in managing diabetic peripheral neuropathy (DPN). Nevertheless, the precise mechanism of its action remains enigmatic.PurposeThe primary objective of this investigation is to employ a bioinformatics-driven approach combined with network pharmacology to comprehensively explore the therapeutic mechanism of XBF in the context of DPN.Study design and MethodsThe active chemicals and their respective targets of XBF were sourced from the TCMSP and BATMAN databases. Differentially expressed genes (DEGs) related to DPN were obtained from the GEO database. The targets associated with DPN were compiled from the OMIM, GeneCards, and DrugBank databases. The analysis of GO, KEGG pathway enrichment, as well as immuno-infiltration analysis, was conducted using the R language. The investigation focused on the distribution of therapeutic targets of XBF within human organs or cells. Subsequently, molecular docking was employed to evaluate the interactions between potential targets and active compounds of XBF concerning the treatment of DPN.ResultsThe study successfully identified a total of 122 active compounds and 272 targets associated with XBF. 5 core targets of XBF for DPN were discovered by building PPI network. According to GO and KEGG pathway enrichment analysis, the mechanisms of XBF for DPN could be related to inflammation, immune regulation, and pivotal signalling pathways such as the TNF, TLR, CLR, and NOD-like receptor signalling pathways. These findings were further supported by immune infiltration analysis and localization of immune organs and cells. Moreover, the molecular docking simulations demonstrated a strong binding affinity between the active chemicals and the carefully selected targets.ConclusionIn summary, this study proposes a novel treatment model for XBF in DPN, and it also offers a new perspective for exploring the principles of traditional Chinese medicine (TCM) in the clinical management of DPN.
Oral Chinese Herbal Medicine plus usual care for diabetic kidney disease: study protocol for a randomized, double-blind, placebo-controlled pilot trial
Authors: Liu Meifang , Di Yuan Ming , Zhang Lei , Yang Lihong , Zhang La , Chen Junhui , Wang Ruobing , Xie Xiaoning , Lan Fang , Xie Liping , Huang Juan , Zhang Anthony Lin , Xue Charlie Changli , Liu Xusheng 
Published: February 2024

BackgroundDiabetic kidney disease (DKD) has become the leading cause of kidney failure, causing a significant socioeconomic burden worldwide. The usual care for DKD fails to achieve satisfactory effects in delaying the persistent loss of renal function. A Chinese herbal medicine, Tangshen Qushi Formula (TQF), showed preliminary clinical benefits with a sound safety profile for people with stage 2-4 DKD. We present the protocol of an ongoing clinical trial investigating the feasibility, efficacy, and safety of TQF compared to placebo in delaying the progressive decline of renal function for people with stage 2-4 DKD.MethodsA mixed methods research design will be used in this study. A randomized, double-blind, placebo-controlled pilot trial will evaluate the feasibility, efficacy, and safety of TQF compared to placebo on kidney function for people with stage 2-4 DKD. An embedded semi-structured interview will explore the acceptability of TQF granules and trial procedures from the participant’s perspective. Sixty eligible participants with stage 2-4 DKD will be randomly allocated to the treatment group (TQF plus usual care) or the control group (TQF placebo plus usual care) at a 1:1 ratio for 48-week treatment and 12-week follow-up. Participants will be assessed every 12 weeks. The feasibility will be assessed as the primary outcome. The changes in the estimated glomerular filtration rate, urinary protein/albumin, renal function, glycemic and lipid markers, renal composite endpoint events, and dampness syndrome of Chinese medicine will be assessed as the efficacy outcomes. Safety outcomes such as liver function, serum potassium, and adverse events will also be evaluated. The data and safety monitoring board will be responsible for the participants’ benefits, the data’s credibility, and the results’ validity. The intent-to-treat and per-protocol analysis will be performed as the primary statistical strategy.DiscussionConducting a rigorously designed pilot trial will be a significant step toward establishing the feasibility and acceptability of TQF and trial design. The study will also provide critical information for future full-scale trial design to further generate new evidence supporting clinical practice for people with stage 2-4 DKD.Trial registration numberhttps://www.chictr.org.cn/, identifier ChiCTR2200062786.
Peripheral blood mononuclear cell low molecular mass protein 7 in acute ischemic stroke: vertical change from admission to discharge and correlation with disability, stroke recurrence, and death
Authors: Hou Lujia , Zhang Yanlei 
Published: February 2024

ObjectiveLow molecular mass protein 7 (LMP7) aggravates abnormal T cell differentiation and atherosclerosis, but its clinical role in acute ischemic stroke (AIS) is still unclear. This study aimed to investigate the correlation of peripheral blood mononuclear cell (PBMC) LMP7 with T cell subsets, disease severity, and prognosis in AIS patients.MethodsA total of 162 AIS patients were enrolled for detecting PBMC LMP7 and T helper (Th) 1, Th2, and Th17 cells via reverse transcriptase-polymerase chain reaction and flow cytometry, respectively. In addition, PBMC LMP7 at discharge was also quantified.ResultsIncreased LMP7 at admission was associated with decreased Th2 cells (P=0.014), elevated Th17 cells (P&lt;0.001), C-reactive protein (P=0.005), National Institutes of Health Stroke Scale (NIHSS) score (P=0.007), and disease severity (defined by NIHSS score) (P=0.010). LMP7 at admission reflected a high risk of stroke recurrence (area under curve (AUC): 0.748, 95% confidence interval (CI): 0.564-0.932), but not mRS score at month 3 (M3) &gt;2 (AUC: 0.585, 95%CI: 0.479-0.691), or death (AUC: 0.723, 95%CI: 0.338-1.000). LMP7 at discharge was reduced compared to that at admission (P&lt;0.001). LMP7 at discharge was positively correlated with the risk of stroke recurrence (AUC: 0.849, 95%CI: 0.735-0.963) and death (AUC: 0.919, 95%CI: 0.836-1.000), but had a weak capacity to reflect mRS score at M3 &gt;2 (AUC: 0.671, 95%CI: 0.578-0.765).ConclusionPBMC LMP7 positively correlates with Th17 cells, inflammation, and disease severity in AIS patients, meanwhile, its level at discharge shows a good ability to reflect the risks of stroke recurrence and death.
Mismatch repair gene MSH6 correlates with the prognosis, immune status and immune checkpoint inhibitors response of endometrial cancer
Authors: Zhou Lin-Zhi , Xiao Hong-Qi , Chen Jie 
Published: February 2024

ObjectiveMany patients treated with immune checkpoint inhibitors (ICIs) developed primary or secondary drug resistance for unknown reasons. This study investigates whether mismatch repair (MMR) genes are responsible for this therapeutic restriction.MethodsWe obtained the transcriptional, clinical and single nucleotide polymorphism data for endometrial cancer (EC) from The Cancer Genome Atlas and the immunophenoscore data of EC from The Cancer Immunome Atlas, then analyzed in R to evaluate the relationship between MMR genes and clinicopathological features, prognosis, immune infiltration, immune checkpoint expression and responsiveness to ICIs in EC. We used differentially expressed genes in the MSH6 high and low expression groups to conduct GO and KEGG analyses to explore the impact of MSH6 on the biological functions of EC. Finally, we verified the bioinformatics results with in vitro experiments.ResultsOur analyses showed that compared with the high MSH6 expression group, the low MSH6 expression group had better survival outcomes and less aggressive clinicopathological features. In the multivariate Cox analysis, MSH6 was the only independent risk factor that could predict the prognosis of EC. Besides, the low MSH6 expression group also had a higher immune score, more active immune infiltration and higher immune checkpoint expression, resulting in better responsiveness to ICIs treatment, consistent with the enrichment of GO terms and KEGG pathways related to immune response in this group. Meanwhile, the GO and KEGG enrichment results of the MSH6 high expression group were associated with cell cycle, DNA damage repair and tumorigenesis. To exclude the influence of MSH6 mutations, we performed the previous analyses on the MSH6 wild-type tumor samples and obtained consistent results. In vitro experiments also confirmed that after knocking down MSH6 in endometrial cancer cells, their proliferation, migration and invasion abilities were weakened, while the expression levels of PD-L1 and PD-L2 were elevated. In comparison, overexpression of MSH6 showed an opposite trend.ConclusionReduced MSH6 expression could serve as a potential biomarker for predicting better prognosis, active immune status, higher immune checkpoint expression level and better responsiveness to ICIs treatment in EC. MSH6 may become a potential target for treating solid tumors.
Guanylate-binding protein-5 is involved in inflammasome activation by bacterial DNA but only the cooperation of multiple GBPs accounts for control of Brucella abortus infection
Authors: Marinho Fabio V. , Brito Camila , de Araujo Ana Carolina V. S. C. , Oliveira Sergio C. 
Published: February 2024

IntroductionGuanylate-binding proteins (GBPs) are produced in response to pro-inflammatory signals, mainly interferons. The most studied cluster of GBPs in mice is on chromosome 3. It comprises the genes for GBP1-to-3, GBP5 and GBP7. In humans, all GBPs are present in a single cluster on chromosome 1. Brucella abortus is a Gram-negative bacterium known to cause brucellosis, a debilitating disease that affects both humans and animals. Our group demonstrated previously that GBPs present on murine chromosome 3 (GBPchr3) is important to disrupt Brucella-containing vacuole and GBP5 itself is important to Brucella intracellular LPS recognition. In this work, we investigated further the role of GBPs during B. abortus infection.Methods and resultsWe observed that all GBPs from murine chromosome 3 are significantly upregulated in response to B. abortus infection in mouse bone marrow-derived macrophages. Of note, GBP5 presents the highest expression level in all time points evaluated. However, only GBPchr3-/- cells presented increased bacterial burden compared to wild-type macrophages. Brucella DNA is an important Pathogen-Associated Molecular Pattern that could be available for inflammasome activation after BCV disruption mediated by GBPs. In this regard, we observed reduced IL-1β production in the absence of GBP2 or GBP5, as well as in GBPchr3-/- murine macrophages. Similar result was showed by THP-1 macrophages with downregulation of GBP2 and GBP5 mediated by siRNA. Furthermore, significant reduction on caspase-1 p20 levels, LDH release and Gasdermin-D conversion into its mature form (p30 N-terminal subunit) was observed only in GBPchr3-/- macrophages. In an in vivo perspective, we found that GBPchr3-/- mice had increased B. abortus burden and higher number of granulomas per area of liver tissue, indicating increased disease severity.Discussion/conclusionAltogether, these results demonstrate that although GBP5 presents a high expression pattern and is involved in inflammasome activation by bacterial DNA in macrophages, the cooperation of multiple GBPs from murine chromosome 3 is necessary for full control of Brucella abortus infection.
Evaluation of a creatinine clearance correction equation based on body fat mass in older Japanese patients with diabetes
Authors: Utsumi Sara , Kondo Yuki , Harada Yoshihiko , Yoshida Akira , Nishimura Hiroyuki , Narita Yuki , Irie Tetsumi , Jinnouchi Hideaki , Ishitsuka Yoichi , Hirata Sumio 
Published: February 2024

BackgroundThe estimation of creatinine clearance (CCr) in older adult patients with diabetes is subject to deviations from the results of actual measurements because of changes in body composition. In the present study, we aimed to create a correction for the equation used for the estimation of CCr in older adult Asian patients with diabetes using body composition parameters.MethodsWe enrolled 50 older Japanese patients with diabetes in whom the measured values of CCr were compared with values estimated using the Cockcroft-Gault equation. The relationships between the error in the estimated CCr and body composition parameters were investigated, and the Cockcroft-Gault equation was corrected using the appropriate parameters. To evaluate the generalizability of the corrected equation, the utility of the Cockcroft-Gault equation, which was corrected on the basis of body composition measured using a household body composition meter, was also investigated.ResultsBody fat mass (BFM) was closely correlated with the error in the estimated CCr. The BFM-corrected Cockcroft-Gault equation was more accurate than the original equation. Similarly, the error became smaller using BFM measured with a household body composition meter.ConclusionThe BFM-corrected Cockcroft-Gault equation may provide an accurate method of estimating CCr that can be used in general practice.
Failure to reduce the risk of postoperative lower genital tract infection with perioperative antibiotic prophylaxis during induced abortion: a real-world study
Authors: Ding Jing , Zhang Yan , Gu XiangYing , Che Yan 
Published: February 2024

ObjectiveThis study aimed to evaluate perioperative antibiotic use for induced abortion and its association with lower genital tract infections (LGTI) two weeks post-surgery in China.MethodsWe conducted a prospective cohort study of women seeking induced abortion. We interviewed participants on the day of surgery and two weeks after, and evaluated preoperative tests, gynecological exams, perioperative antibiotic usage, postoperative vaginal microbiota, and LGTI diagnosis. Multivariate logistic regression was used to assess the association between the perioperative antibiotic use and LGTI risk.ResultsWe recruited 8,190 women undergoing induced abortion at 27 participating hospitals. Of these, 95% had gynecological exams, but over 80% lacked tests for vaginal microbiota, chlamydia, and gonorrhea. Approximately 20% of those examined had increased vaginal discharge and abnormal vaginal cleanliness. The positive rates for gram-positive rods, fungi, and trichomonas were 38.6, 2.4, and 0.3%, respectively. More than three-quarters (78.5%) of participants received antibiotics, mainly second-gen cephalosporins (36.8%) and nitroimidazoles (12.3%). LGTI rates two weeks post-surgery were 2.7% for antibiotic recipients and 3.1% for non-recipients, with no statistically significant difference (p &gt; 0.05). Logistic regression showed no association between perioperative antibiotic use and LGTI risk (OR = 1.01, 95% CI 0.59–1.74). However, this risk increased with abnormal preoperative discharge tests (OR = 1.39, 95% CI 1.04–1.86).ConclusionMost Chinese women undergoing induced abortion used perioperative antibiotics, but this did not significantly reduce LGTI risk. Instead, this risk was related to abnormal preoperative discharge tests. Standardization of perioperative antibiotic use for induced abortion is recommended, and prophylactic treatment in Chinese abortion services warrants further investigation.
The incremental value of Mycobacterium tuberculosis trace nucleic acid detection in CT-guided percutaneous biopsy needle rinse solutions for the diagnosis of tuberculosis
Authors: Li Zihui , Wang Bing , Du Boping , Sun Qi , Wang Dongpo , Wei Rongrong , Li Chenghai , Zhu Chuanzhi , Jia Hongyan , Xing Aiying , Zhang Zongde , Pan Liping , Hou Dailun 
Published: February 2024

IntroductionTuberculosis (TB) diagnosis still faces challenges with high proportion of bacteriologic test negative incidences worldwide. We assessed the diagnostic value of digital PCR (dPCR) analysis of ultramicro Mycobacterium tuberculosis (M.tb) nucleic acid in CT-guided percutaneous biopsy needle rinse solution (BNRS) for TB.MethodsBNRS specimens were consecutively collected and total DNA was purified. The concentrations of M.tb-specific IS6110 and IS1081 were quantified using droplet dPCR. The diagnostic performances of BNRS-dPCR and its sensitivity in comparison with conventional tests were analyzed.ResultsA total of 106 patients were enrolled, 63 of whom were TB (48 definite and 15 clinically suspected TB) and 43 were non-TB. The sensitivity of BNRS IS6110 OR IS1081-dPCR for total, confirmed and clinically suspected TB was 66.7%, 68.8% and 60.0%, respectively, with a specificity of 97.7%. Its sensitivity was higher than that of conventional etiological tests, including smear microscopy, mycobacterial culture and Xpert using sputum and BALF samples. The positive detection rate in TB patients increased from 39.3% for biopsy AFB test alone to 73.2% when combined with BNRS-dPCR, and from 71.4% for biopsy M.tb molecular detection alone to 85.7% when combined with BNRS-dPCR.ConclusionOur results preliminarily indicated that BNRS IS6110 OR IS1081-dPCR is a feasible etiological test, which has the potential to be used as a supplementary method to augment the diagnostic yield of biopsy and improve TB diagnosis.