bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lipids, apolipoproteins and gestational diabetes mellitus: a Mendelian randomization study
Authors: Shan Dan , Wang Ao , Yi Ke 
Published: May 2024

Abstract
Background
This study investigates the causal relationship between lipid traits and GDM in an effort to better understand the aetiology of GDM.

Methods
Employing a two-sample Mendelian Randomization (MR) framework, we used Single Nucleotide Polymorphisms (SNPs) as instrumental variables to examine the impact of lipids and apolipoproteins on GDM. The research comprised univariable and multivariable MR analyses, with a prime focus on individual and combined effects of lipid-related traits. Statistical techniques included the fixed-effect inverse variance weighted (IVW) method and supplementary methods such as MR-Egger for comprehensive assessment.

Results
Our findings revealed the following significant associations: apoA-I and HDL cholesterol were inversely correlated with GDM risk, while triglycerides showed a positive correlation. In multivariable analysis, apoA-I consistently exhibited a strong causal link with GDM, even after adjusting for other lipids and Body Mass Index (BMI).

Conclusion
The study demonstrates a significant causal relationship between apoA-I and GDM risk.
Tenascin C as a novel zinc finger protein 750 target regulating the immunogenicity via DNA damage in lung squamous cell carcinoma
Authors: Xia Lu , Lin Hexin , Cao Huifen , Lian Jiabian 
Published: May 2024

AbstractModulation of DNA damage repair in lung squamous cell carcinoma (LUSC) can result in the generation of neoantigens and heightened immunogenicity. Therefore, understanding DNA damage repair mechanisms holds significant clinical relevance for identifying targets for immunotherapy and devising therapeutic strategies. Our research has unveiled that the tumor suppressor zinc finger protein 750 (ZNF750) in LUSC binds to the promoter region of tenascin C (TNC), leading to reduced TNC expression. This modulation may impact the malignant behavior of tumor cells and is associated with patient prognosis. Additionally, single-cell RNA sequencing (scRNA-seq) of LUSC tissues has demonstrated an inverse correlation between ZNF750/TNC expression levels and immunogenicity. Manipulation of the ZNF750-TNC axis in vitro within LUSC cells has shown differential sensitivity to CD8+cells, underscoring its pivotal role in regulating cellular immunogenicity. Further transcriptome sequencing analysis, DNA damage repair assay, and single-strand break analyses have revealed the involvement of the ZNF750-TNC axis in determining the preference for homologous recombination (HR) repair or non-homologous end joining (NHEJ) repair of DNA damage. with involvement of the Hippo/ERK signaling pathway. In summary, this study sheds light on the ZNF750-TNC axis's role in DNA damage repair regulation in LUSC, laying a groundwork for future translational research in immune cell therapy for LUSC.
WNT3 promotes chemoresistance to 5-Fluorouracil in oral squamous cell carcinoma via activating the canonical β-catenin pathway
Authors: Zhang Xuyang , Sun Kairui , Gan Ruihuan , Yan Yuxiang , Zhang Chaochao , Zheng Dali , Lu Youguang 
Published: May 2024

Abstract
Background
5-Fluorouracil (5FU) is a primary chemotherapeutic agent used to treat oral squamous cell carcinoma (OSCC). However, the development of drug resistance has significantly limited its clinical application. Therefore, there is an urgent need to determine the mechanisms underlying drug resistance and identify effective targets. In recent years, the Wingless and Int-1 (WNT) signaling pathway has been increasingly studied in cancer drug resistance; however, the role of WNT3, a ligand of the canonical WNT signaling pathway, in OSCC 5FU-resistance is not clear. This study delved into this potential connection.

Methods
5FU-resistant cell lines were established by gradually elevating the drug concentration in the culture medium. Differential gene expressions between parental and resistant cells underwent RNA sequencing analysis, which was then substantiated via Real-time quantitative PCR (RT-qPCR) and western blot tests. The influence of the WNT signaling on OSCC chemoresistance was ascertained through WNT3 knockdown or overexpression. The WNT inhibitor methyl 3-benzoate (MSAB) was probed for its capacity to boost 5FU efficacy.

Results
In this study, the WNT/β-catenin signaling pathway was notably activated in 5FU-resistant OSCC cell lines, which was confirmed through transcriptome sequencing analysis, RT-qPCR, and western blot verification. Additionally, the key ligand responsible for pathway activation, WNT3, was identified. By knocking down WNT3 in resistant cells or overexpressing WNT3 in parental cells, we found that WNT3 promoted 5FU-resistance in OSCC. In addition, the WNT inhibitor MSAB reversed 5FU-resistance in OSCC cells.

Conclusions
These data underscored the activation of the WNT/β-catenin signaling pathway in resistant cells and identified the promoting effect of WNT3 upregulation on 5FU-resistance in oral squamous carcinoma. This may provide a new therapeutic strategy for reversing 5FU-resistance in OSCC cells.
Correlation of gasdermin B staining patterns with prognosis, progression, and immune response in colorectal cancer
Authors: Sun Liang , Wang Jiahui , Li Yuxuan , Kang Yixin , Jiang Yi , Zhang Jun , Qian Senmi , Xu Fangying 
Published: May 2024

Abstract
Background
Pyroptosis is a type of programmed cell death mediated by the gasdermin family. Gasdermin B (GSDMB), as a member of gasdermin family, can promote the occurrence of cell pyroptosis. However, the correlations of the GSDMB expression in colorectal cancer with clinicopathological predictors, immune microenvironment, and prognosis are unclear.

Methods
Specimens from 267 colorectal cancer cases were analyzed by immunohistochemistry to determine GSDMB expression, CD3+, CD4+, and CD8+ T lymphocytes, CD20+ B lymphocytes, CD68+ macrophages, and S100A8+ immune cells. GSDMB expression in cancer cells was scored in the membrane, cytoplasm, and nucleus respectively. GSDMB+ immune cell density was calculated. Univariate and multivariate survival analyses were performed. The association of GSDMB expression with other clinicopathological variables and immune cells were also analyzed. Double immunofluorescence was used to identify the nature of GSDMB+ immune cells. Cytotoxicity assays and sensitivity assays were performed to detect the sensitivity of cells to 5-fluorouracil.

Results
Multivariate survival analysis showed that cytoplasmic GSDMB expression was an independent favorable prognostic indicator. Patients with positive cytoplasmic or nuclear GSDMB expression would benefit from 5-fluorouracil based chemotherapy. The assays in vitro showed that high GSDMB expression enhanced the sensitivity of colorectal cancer cells to 5-fluorouracil. Patients with positive membranous or nuclear GSDMB expression had more abundant S100A8+ immune cells in the tumor invasive front. Positive nuclear GSDMB expression indicated more CD68+ macrophages in the tumor microenvironment. Moreover, GSDMB+ immune cell density in the stroma was associated with a higher neutrophil percentage but a lower lymphocyte counts and monocyte percentage in peripheral blood. Furthermore, the results of double immunofluorescence showed that GSDMB co-expressed with CD68 or S100A8 in stroma cells.

Conclusion
The GSDMB staining patterns are linked to its role in cancer progression, the immune microenvironment, systemic inflammatory response, chemotherapeutic efficacy, and prognosis. Colorectal cancer cells with high GSDMB expression are more sensitive to 5-fluorouracil. However, GSDMB expression in immune cells has different effects on cancer progression from that in cancer cells.
The contribution and interplay of implicit and explicit processes on physical activity behavior: empirical testing of the physical activity adoption and maintenance (PAAM) model
Authors: Jekauc Darko , Gürdere Ceren , Englert Chris , Strobach Tilo , Bottesi Gioia , Bray Steven , Brown Denver , Fleig Lena , Ghisi Marta , Graham Jeffrey , Martinasek Mary , Tamulevicius Nauris , Pfeffer Ines 
Published: May 2024

AbstractThe adoption and maintenance of physical activity (PA) is an important health behavior. This paper presents the first comprehensive empirical test of the Physical Activity Adoption and Maintenance (PAAM) model, which proposes that a combination of explicit (e.g., intention) and implicit (e.g., habit,, affect) self-regulatory processes is involved in PA adoption and maintenance. Data were collected via online questionnaires in English, German, and Italian at two measurement points four weeks apart. The study included 422 participants (Mage= 25.3, SDage= 10.1; 74.2% women) from Germany, Switzerland, Italy, Canada, and the U.S. The study results largely supported the assumptions of the PAAM model, indicating that intentions and habits significantly mediate the effects of past PA on future PA. In addition, the effect of past PA on future PA was shown to be significant through a mediation chain involving affect and habit. Although the hypothesis that trait self-regulation moderates the intention-behavior relationship was not supported, a significant moderating effect of affect on the same relationship was observed. The results suggest that interventions targeting both explicit and implicit processes may be effective in promoting PA adoption and maintenance.
YTHDF2-Mediated m6A methylation inhibition by miR27a as a protective mechanism against hormonal osteonecrosis in BMSCs
Authors: Yuan Tianyi , Liu Hongjiang , Abudoukadier Maimaitiyibubaji , Yang Zengqiang , Zhou Zhiheng , Cui Yong 
Published: May 2024

Abstract
Background
With the increasing incidence of steroid-induced necrosis of the femoral head (SNFH), numerous scholars have investigated its pathogenesis. Current evidence suggests that the imbalance between lipogenesis and osteoblast differentiation in bone marrow mesenchymal stem cells (BMSCs) is a key pathological feature of SNFH. MicroRNAs (miRNAs) have strong gene regulatory effects and can influence the direction of cell differentiation. N6-methyladenosine (m6A) is a prevalent epigenetic modification involved in diverse pathophysiological processes. However, knowledge of how miRNAs regulate m6A-related factors that affect BMSC differentiation is limited.

Objective
We aimed to investigate the role of miR27a in regulating the expression of YTHDF2 in BMSCs.

Methods
We compared miR27a, YTHDF2, and total m6A mRNA levels in SNFH-affected and control BMSCs. CCK-8 and TUNEL assays were used to assess BMSC proliferation and apoptosis. Western blotting and qRT‒PCR were used to measure the expression of osteogenic (ALP, RUNX2, and OCN) and lipogenic (PPARγ and C/EBPα) markers. Alizarin Red and Oil Red O staining were used to quantify osteogenic and lipogenic differentiation, respectively. miR27a was knocked down or overexpressed to evaluate its impact on BMSC differentiation and its relationship with YTHDF2. Bioinformatics analyses identified YTHDF2 as a differentially expressed gene in SNFH (ROC analysis) and revealed potential signaling pathways through GSEA. The effects of YTHDF2 silencing on the lipogenic and osteogenic functions of BMSCs were assessed.

Results
miR27a downregulation and YTHDF2 upregulation were observed in the SNFH BMSCs. miR27a knockdown/overexpression modulated YTHDF2 expression, impacting BMSC differentiation. miR27a silencing decreased m6A methylation and promoted osteogenic differentiation, while YTHDF2 silencing exerted similar effects. GSEA suggested potential signaling pathways associated with YTHDF2 in SNFH.

Conclusion
miR27a regulates BMSC differentiation through YTHDF2, affecting m6A methylation and promoting osteogenesis. This finding suggests a potential therapeutic target for SNFH.
Machine learning-empowered sleep staging classification using multi-modality signals
Authors: Satapathy Santosh Kumar , Brahma Biswajit , Panda Baidyanath , Barsocchi Paolo , Bhoi Akash Kumar 
Published: May 2024

AbstractThe goal is to enhance an automated sleep staging system's performance by leveraging the diverse signals captured through multi-modal polysomnography recordings. Three modalities of PSG signals, namely electroencephalogram (EEG), electrooculogram (EOG), and electromyogram (EMG), were considered to obtain the optimal fusions of the PSG signals, where 63 features were extracted. These include frequency-based, time-based, statistical-based, entropy-based, and non-linear-based features. We adopted the ReliefF (ReF) feature selection algorithms to find the suitable parts for each signal and superposition of PSG signals. Twelve top features were selected while correlated with the extracted feature sets' sleep stages. The selected features were fed into the AdaBoost with Random Forest (ADB + RF) classifier to validate the chosen segments and classify the sleep stages. This study's experiments were investigated by obtaining two testing schemes: epoch-wise testing and subject-wise testing. The suggested research was conducted using three publicly available datasets: ISRUC-Sleep subgroup1 (ISRUC-SG1), sleep-EDF(S-EDF), Physio bank CAP sleep database (PB-CAPSDB), and S-EDF-78 respectively. This work demonstrated that the proposed fusion strategy overestimates the common individual usage of PSG signals.
Drivers of district-level differences in outpatient antibiotic prescribing in Germany: a qualitative study with prescribers
Authors: Schüz Benjamin , Scholle Oliver , Haug Ulrike , Tillmann Roland , Jones Christopher 
Published: May 2024

Abstract
Background
Previous studies have identified substantial regional variations in outpatient antibiotic prescribing in Germany, both in the paediatric and adult population. This indicates inappropriate antibiotic prescribing in some regions, which should be avoided to reduce antimicrobial resistance and potential side effects. The reasons for regional variations in outpatient antibiotic prescribing are not yet completely understood; socioeconomic and health care density differences between regions do not fully explain such differences. Here, we apply a behavioural perspective by adapting the Theoretical Domains Framework (TDF) to examine regional factors deemed relevant for outpatient antibiotic prescriptions by paediatricians and general practitioners.

Methods
Qualitative study with guideline-based telephone interviews of 40 prescribers (paediatricians and general practitioners) in outpatient settings from regions with high and low rates of antibiotic prescriptions, stratified by urbanity. TDF domains formed the basis of an interview guide to assess region-level resources and barriers to rational antibiotic prescription behaviour. Interviews lasted 30–61 min (M = 45 min). Thematic analysis was used to identify thematic clusters, and relationships between themes were explored through proximity estimation.

Results
Both paediatricians and general practitioners in low-prescribing regions reported supporting contextual factors (in particular good collegial networks, good collaboration with laboratories) and social factors (collegial support and low patient demand for antibiotics) as important resources. In high-prescribing regions, poor coordination between in-patient and ambulatory health services, lack of region-level information on antimicrobial resistance, few professional development opportunities, and regional variations in patient expectations were identified as barriers to rational prescribing behaviour.

Conclusions
Interventions targeting professional development, better collaboration structures with laboratories and clearer and user-friendly guidelines could potentially support rational antibiotic prescribing behaviour. In addition, better networking and social support among physicians could support lower prescription rates.
An integrated cofactor and co-substrate recycling pathway for the biosynthesis of 1,5-pentanediol
Authors: Hua Wenfeng , Liang Bo , Zhou Suhui , Zhang Qiushui , Xu Shuang , Chen Kequan , Wang Xin 
Published: May 2024

Abstract
Background
1,5-pentanediol (1,5-PDO) is a linear diol with an odd number of methylene groups, which is an important raw material for polyurethane production. In recent years, the chemical methods have been predominantly employed for synthesizing 1,5-PDO. However, with the increasing emphasis on environmentally friendly production, it has been a growing interest in the biosynthesis of 1,5-PDO. Due to the limited availability of only three reported feasible biosynthesis pathways, we developed a new biosynthetic pathway to form a cell factory in Escherichia coli to produce 1,5-PDO.

Results
In this study, we reported an artificial pathway for the synthesis of 1,5-PDO from lysine with an integrated cofactor and co-substrate recycling and also evaluated its feasibility in E.coli. To get through the pathway, we first screened aminotransferases originated from different organisms to identify the enzyme that could successfully transfer two amines from cadaverine, and thus GabT from E. coli was characterized. It was then cascaded with lysine decarboxylase and alcohol dehydrogenase from E. coli to achieve the whole-cell production of 1,5-PDO from lysine. To improve the whole-cell activity for 1,5-PDO production, we employed a protein scaffold of EutM for GabT assembly and glutamate dehydrogenase was also validated for the recycling of NADPH and α-ketoglutaric acid (α-KG). After optimizing the cultivation and bioconversion conditions, the titer of 1,5-PDO reached 4.03 mM.

Conclusion
We established a novel pathway for 1,5-PDO production through two consecutive transamination reaction from cadaverine, and also integrated cofactor and co-substrate recycling system, which provided an alternative option for the biosynthesis of 1,5-PDO.
Real-world effectiveness of a new powered stapling system with gripping surface technology on the intraoperative clinical and economic outcomes of gastrectomy for gastric cancer
Authors: Guo Honghai , Zheng Tao , Lin Yecheng , Tang Tiange , Zhang Zhidong , Wang Dong , Zhao Xuefeng , Liu Yu , Tan Bibo , Yang Peigang , Tian Yuan , Li Yong , Zhao Qun 
Published: May 2024

Abstract
Background
Surgical staplers have been widely used to facilitate surgeries, and this study aimed to examine the real-world effectiveness of a new powered stapling system with Gripping Surface Technology (GST) on intraoperative outcomes of gastrectomy for gastric cancer.

Method
The data were extracted from the Fourth Hospital of Hebei Medical University’s (FHHMU) medical records system. Participants (N = 121 patients) were classified into the GST (n = 59) or non-GST group (n = 62), based on the use of the GST system. The intraoperative outcomes such as bleeding were assessed by reviewing video records. T-tests, Chi-square tests, and Mann–Whitney-U tests were used to compare the baseline characteristics between groups. Multivariate logistic regression was conducted for adjusting outcomes to study the effect of variables.

Results
Compared with the non-GST group, the GST group had significantly lower risks for intraoperative bleeding, intraoperative anastomosis intervention rate, intraoperative suture, and intraoperative pression (aORs: 0.0853 (p < 0.0001), 0.076 (p = 0.0003), 0.167 (p = 0.0012), and 0.221 (p = 0.0107), respectively). The GST group also consumed one fewer cartridge than the non-GST group (GST:5 vs non-GST: 6, p = 0.0241).

Conclusion
The use of the GST system was associated with better intraoperative outcomes and lower cartridge consumption in Chinese real-world settings.
Chronic atrophic gastritis and risk of incident upper gastrointestinal cancers: a systematic review and meta-analysis
Authors: Li Junqiu , Pan Jielu , Xiao Dinghong , Shen Nan , Wang Ruiqing , Miao Hongyv , Pu Peimin , Zhang Haiyan , Yv Xiao , Xing Lianjun 
Published: May 2024

AbstractBackgroundPrevious literature has explored the relationship between chronic atrophic gastritis (CAG) and isolated cancers within the upper gastrointestinal cancers; However, an integrative synthesis across the totality of upper gastrointestinal cancers was conspicuously absent. The research objective was to assess the relationship between CAG and the risk of incident upper gastrointestinal cancers, specifically including gastric cancer, oesophageal cancer, and oesophagogastric junction cancer.MethodsRigorous systematic searches were conducted across three major databases, namely PubMed, Embase and Web of Science, encompassing the timeline from database inception until August 10, 2023. We extracted the necessary odds ratio (OR) and their corresponding 95% confidence interval (CI) for subsequent meta-analysis. Statistical analyses were conducted using Stata 17.0 software.ResultsThis meta-analysis included a total of 23 articles encompassing 5858 patients diagnosed with upper gastrointestinal cancers. CAG resulted in a statistically significant 4.12-fold elevated risk of incident gastric cancer (OR = 4.12, 95% CI 3.20–5.30). Likewise, CAG was linked to a 2.08-fold increased risk of incident oesophageal cancer (OR = 2.08, 95%CI 1.60–2.72). Intriguingly, a specific correlation was found between CAG and the risk of incident oesophageal squamous cell carcinoma (OR = 2.29, 95%CI 1.77–2.95), while no significant association was detected for oesophageal adenocarcinoma (OR = 0.62, 95%CI 0.17–2.26). Moreover, CAG was correlated with a 2.77-fold heightened risk of oesophagogastric junction cancer (OR = 2.77, 95%CI 2.21–3.46). Notably, for the same type of upper gastrointestinal cancer, it was observed that diagnosing CAG through histological methods was linked to a 33–77% higher risk of developing cancer compared to diagnosing CAG through serological methods.ConclusionThis meta-analysis indicated a two- to fourfold increased risk of gastric cancer, oesophageal cancer, and oesophagogastric junction cancer in patients with CAG. Importantly, for the same upper gastrointestinal cancer, the risk of incident cancer was higher when CAG was diagnosed histologically compared to serological diagnosis. Further rigorous study designs are required to explore the impact of CAG diagnosed through both diagnostic methods on the risk of upper gastrointestinal cancers.