bluuebunny/crossref_metadata_2025_split huggingface dataset:
Waist-corrected BMI predicts incident diabetes mellitus in a population-based observational cohort study
Authors: Wang Nana , Li Yuying , Guo Chuanji 
Published: June 2023

IntroductionWaist-corrected body mass index (wBMI), which combines BMI and waist circumference (WC) measurements, has proven superior to either measure alone for predicting obesity but has not yet been applied to the prediction of diabetes mellitus (DM).MethodsOver a 5-year period, 305,499 subjects were eligible for this study based on citizen health check-ups in the Tacheng Area of northwest China. Diagnosis of DM was defined as the end point.ResultsAfter exclusion, a total of 111,851 subjects were included in the training cohort and 47,906 in the validation cohort. Participants of both sexes with wBMI in the upper quartiles had significantly higher incidence of DM than those with wBMI in the lower quartiles (log-rank χ2 = 236, p&lt; 0.001 for men; log-rank χ2 = 304, p&lt; 0.001 for women). After adjusting for multiple variables, WC, BMI, wBMI, and waist-to-height ratio (WHtR) were all independent predictors for diabetes. In men, the adjusted hazard ratios (HRs) of wBMI for diabetes for the second, third, and fourth quartiles were 1.297 [95% CI: 1.157, 1.455], 1.664 [95% CI: 1.493, 1.853], and 2.132 [95% CI: 1.921, 2.366], respectively, when compared with the first quartile. In women, they were 1.357 [95% CI: 1.191, 1.546], 1.715 [95% CI: 1.517, 1.939], and 2.262 [95% CI: 2.010, 2.545], respectively. Compared with WC, BMI, and WHtR, wBMI had the highest C-index in both men (0.679, 95% CI: 0.670, 0.688) and women (0.730, 95% CI: 0.722, 0.739). Finally, a nomogram was constructed to predict incident DM based on wBMI and other variables. In conclusion, wBMI had the strongest predictive capacity for incident DM when compared with WC, BMI, and WHtR, especially in women.DiscussionThis study provides a reference for advanced investigation of wBMI on DM and other metabolic diseases in the future.
A negative association between triglyceride glucose-body mass index and testosterone in adult males: a cross-sectional study
Authors: Wu Shenghao , Wu Yanhong , Fang Lizi , Zhao Junzhao , Cai Yaoyao , Xia Weiting 
Published: June 2023

Background and objectivesInsulin resistance (IR) is closely related to the decline or deficiency of testosterone in males. Triglyceride glucose-body mass (TyG-BMI) is considered to be a novel indicator of IR. We conducted this analysis to investigate the association between TyG-BMI and male testosterone, and to explore whether its ability to predict testosterone deficiency is superior to HOMA-IR and TyG.MethodsThis was a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES, 2011–2016). The TyG-BMI index was calculated from serum triglyceride, fasting plasma glucose and BMI. The association of TyG-BMI with male testosterone was estimated by weighted multivariable regression.ResultsWe included 3394 participants for the final analysis. After adjusting for confounders, TyG-BMI was found to show an independent negative association with testosterone (β=-1.12, 95%CI: -1.50, -0.75, P&lt;0.0001). Multivariate-adjusted beta also showed testosterone levels were significantly lower in the two highest TyG-BMI group (Q3, Q4) compared to the lowest group (Q1). Similar results were seen in all of the subgroup populations by stratified analysis (all P-interaction &gt;0.05). Furthermore, ROC curve analysis indicated that the area under the curve of TyG-BMI index (0.73, 95% CI: 0.71, 0.75) was larger than that of HOMA-IR index (0.71, 95% CI: 0.69, 0.73) and TyG index (0.66, 95% CI: 0.64, 0.68).ConclusionOur result suggested a negative association between TyG-BMI index and testosterone in adult males. The predictability of the TyG-BMI index for testosterone deficiency is better than that of HOMA-IR index and TyG index.
Identifying missing pieces in color vision defects: a genome-wide association study in Silk Road populations
Authors: Nardone Giuseppe Giovanni , Spedicati Beatrice , Concas Maria Pina , Santin Aurora , Morgan Anna , Mazzetto Lorenzo , Battaglia-Parodi Maurizio , Girotto Giorgia 
Published: June 2023

Introduction: Color vision defects (CVDs) are conditions characterized by the alteration of normal trichromatic vision. CVDs can arise as the result of alterations in three genes (OPN1LW, OPN1MW, OPN1SW) or as a combination of genetic predisposition and environmental factors. To date, apart from Mendelian CVDs forms, nothing is known about multifactorial CVDs forms.Materials and Methods: Five hundred and twenty individuals from Silk Road isolated communities were genotyped and phenotypically characterized for CVDs using the Farnsworth D-15 color test. The CVDs traits Deutan-Protan (DP) and Tritan (TR) were analysed. Genome Wide Association Study for both traits was performed, and results were corrected with a False Discovery Rate linkage-based approach (FDR-p). Gene expression of final candidates was investigated using a published human eye dataset, and pathway analysis was performed.Results: Concerning DP, three genes: PIWIL4 (FDR-p: 9.01*10–9), MBD2 (FDR-p: 4.97*10–8) and NTN1 (FDR-p: 4.98*10–8), stood out as promising candidates. PIWIL4 is involved in the preservation of Retinal Pigmented Epithelium (RPE) homeostasis while MBD2 and NTN1 are both involved in visual signal transmission. With regards to TR, four genes: VPS54 (FDR-p: 4.09*10–9), IQGAP (FDR-p: 6,52*10–10), NMB (FDR-p: 8.34*10–11), and MC5R (FDR-p: 2.10*10–8), were considered promising candidates. VPS54 is reported to be associated with Retinitis pigmentosa; IQGAP1 is reported to regulate choroidal vascularization in Age-Related Macular Degeneration; NMB is involved in RPE homeostasis regulation; MC5R is reported to regulate lacrimal gland function.Discussion: Overall, these results provide novel insights regarding a complex phenotype (i.e., CVDs) in an underrepresented population such as Silk Road isolated communities.
Clinical and HLA genotype analysis of immune checkpoint inhibitor-associated diabetes mellitus: a single-center case series from China
Authors: Liu Yi-chen , Liu Hong , Zhao Shao-li , Chen Ke , Jin Ping 
Published: June 2023

ObjectiveTo investigate the clinical characteristics and HLA genotypes of patients with immune checkpoint inhibitor-associated diabetes mellitus (ICI-DM) in China.MethodsWe enrolled 23 patients with ICI-DM and 51 patients with type 1 diabetes (T1D). Clinical characteristics of the patients were collected. HLA-DRB1, HLA-DQA1, and HLA-DQB1 genotyping was conducted via next-generation sequencing.ResultsThe ICI-DM patients had a male predominance (70.6%), a mean body mass index (BMI) of 21.2 ± 3.5 kg/m2, and a mean onset of ICI-DM in 5 (IQR, 3-9) cycles after ICI therapy. Most (78.3%) ICI-DM patients were treated with anti-PD-1, 78.3% presented with diabetic ketoacidosis, and all had low C-peptide levels and received multiple insulin injections. Compared to T1D patients, ICI-DM patients were significantly older (57.2 ± 12.4 vs 34.1 ± 15.7 years) and had higher blood glucose but lower HbA1c levels (P&lt;0.05). Only two (8.7%) ICI-DM patients were positive for islet autoantibodies, which was lower than that in T1D patients (66.7%, P&lt;0.001). A total of 59.1% (13/22) of ICI-DM patients were heterozygous for an HLA T1D risk haplotype, and DRB1*0901-DQA1*03-DQB1*0303 (DR9) and DRB1*0405-DQA1*03-DQB1*0401 were the major susceptible haplotypes. Compared to T1D, the susceptible DR3-DQA1*0501-DQB1*0201 (DR3) and DR9 haplotypes were less frequent (17.7% vs 2.3%; P=0.011 and 34.4% vs 15.9%; P=0.025), whereas the protective haplotypes (DRB1*1101-DQA1*05-DQB1*0301 and DRB1*1202-DQA1*0601-DQB1*0301) were more frequent in ICI-DM patients (2.1% vs 13.6%; P=0.006 and 4.2% vs 15.9%; P=0.017). None of the ICI-DM patients had T1D-associated high-risk genotypes DR3/DR3, DR3/DR9, and DR9/DR9. Among the 23 ICI-DM patients, 7 (30.4%) presented with ICI-associated fulminant type 1 diabetes (IFD), and 16 (69.6%) presented with ICI-associated type 1 diabetes (IT1D). Compared to IT1D patients, IFD patients exhibited marked hyperglycemia and low C-peptide and HbA1c levels (P&lt;0.05). Up to 66.7% (4/6) of IFD patients were heterozygous for reported fulminant type 1 diabetes susceptibility HLA haplotypes (DRB1*0405-DQB1*0401 or DRB1*0901-DQB1*0303).ConclusionICI-DM shares similar clinical features with T1D, such as acute onset, poor islet function and insulin dependence. However, the lack of islet autoantibodies, the low frequencies of T1D susceptibility and high frequencies of protective HLA haplotypes indicate that ICI-DM represents a new model distinct from classical T1D.
Establishment and validation of a ubiquitination-related gene signature associated with prognosis in pancreatic duct adenocarcinoma
Authors: Guo Yangyang , Wu Zhixuan , Cen Kenan , Bai Yongheng , Dai Ying , Mai Yifeng , Hong Kai , Qu Liangchen 
Published: June 2023

BackgroundPatients with pancreatic duct adenocarcinoma (PDAC) have varied prognoses that depend on numerous variables. However, additional research is required to uncover the latent impact of ubiquitination-related genes (URGs) on determining PDAC patients’ prognoses.MethodsThe URGs clusters were discovered via consensus clustering, and the prognostic differentially expressed genes (DEGs) across clusters were utilized to develop a signature using a least absolute shrinkage and selection operator (LASSO) regression analysis of data from TCGA-PAAD. Verification analyses were conducted across TCGA-PAAD, GSE57495 and ICGC-PACA-AU to show the robustness of the signature. RT-qPCR was used to verify the expression of risk genes. Lastly, we formulated a nomogram to improve the clinical efficacy of our predictive tool.ResultsThe URGs signature, comprised of three genes, was developed and was shown to be highly correlated with the prognoses of PAAD patients. The nomogram was established by combining the URGs signature with clinicopathological characteristics. We discovered that the URGs signature was remarkably superior than other individual predictors (age, grade, T stage, et al). Also, the immune microenvironment analysis indicated that ESTIMATEscore, ImmuneScores, and StromalScores were elevated in the low-risk group. The immune cells that infiltrated the tissues were different between the two groups, as did the expression of immune-related genes.ConclusionThe URGs signature could act as the biomarker of prognosis and selecting appropriate therapeutic drugs for PDAC patients.
Bioinformatic analysis of hub markers and immune cell infiltration characteristics of gastric cancer
Authors: Li Chao , Yang Tan , Yuan Yu , Wen Rou , Yu Huan 
Published: June 2023

BackgroundGastric cancer (GC) is the fifth most common cancer and the second leading cause of cancer-related deaths worldwide. Due to the lack of specific markers, the early diagnosis of gastric cancer is very low, and most patients with gastric cancer are diagnosed at advanced stages. The aim of this study was to identify key biomarkers of GC and to elucidate GC-associated immune cell infiltration and related pathways.MethodsGene microarray data associated with GC were downloaded from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were analyzed using Gene Ontology (GO), Kyoto Gene and Genome Encyclopedia, Gene Set Enrichment Analysis (GSEA) and Protein−Protein Interaction (PPI) networks. Weighted gene coexpression network analysis (WGCNA) and the least absolute shrinkage and selection operator (LASSO) algorithm were used to identify pivotal genes for GC and to assess the diagnostic accuracy of GC hub markers using the subjects’ working characteristic curves. In addition, the infiltration levels of 28 immune cells in GC and their interrelationship with hub markers were analyzed using ssGSEA. And further validated by RT-qPCR.ResultsA total of 133 DEGs were identified. The biological functions and signaling pathways closely associated with GC were inflammatory and immune processes. Nine expression modules were obtained by WGCNA, with the pink module having the highest correlation with GC; 13 crossover genes were obtained by combining DEGs. Subsequently, the LASSO algorithm and validation set verification analysis were used to finally identify three hub genes as potential biomarkers of GC. In the immune cell infiltration analysis, infiltration of activated CD4 T cell, macrophages, regulatory T cells and plasmacytoid dendritic cells was more significant in GC. The validation part demonstrated that three hub genes were expressed at lower levels in the gastric cancer cells.ConclusionThe use of WGCNA combined with the LASSO algorithm to identify hub biomarkers closely related to GC can help to elucidate the molecular mechanism of GC development and is important for finding new immunotherapeutic targets and disease prevention.
Mapping marine ecosystem services in a multifunctional seascape: the case of Grande Vasière (Bay of Biscay)
Authors: Lavialle Gaël , Boussarie Germain , Kopp Dorothée , Morfin Marie , Mouchet Maud A. 
Published: June 2023

IntroductionCoastal and continental shelf ecosystems are among the most productive, yet exploited, ecosystems. The Grande Vasière (GV) covers most part of the French Northern part of the Bay of Biscay, a crucial fishing ground for metropolitan France. It is the place of numerous uses, especially fishing, and will soon shelter sand extraction activities and offshore windfarms. All these activities may compete for space and resources and put pressure on habitats, biodiversity and subsequent ecosystem services (ES). Current management strategies integrate these activities and biodiversity conservation schemes but no ES.MethodsTo fill that gap, we quantified and mapped nine indicators of ecosystem processes (EP), used as proxies of four ES (i.e. sea food provisioning, biological control, regulation of environmental conditions and life cycle maintenance). Due to the complexity of ES, we investigated several EP by ES. Then we identified hotspots and coldspots of supply and spatial overlap among EP and other uses (conservation, fishing, offshore windfarms and sand extraction).ResultsEP mapping suggests a higher capacity of supply of the chosen ES in the Northern part of the GV. We found a strong spatial heterogeneity among the EP related to the same ES, underlining a point of vigilance when designing management measures to sustain ES supply. Northern EP hotspots overlap with high amounts of bottom trawl fishing effort. Higher levels of commercial species diversity and sole spawning grounds in the South overlap with higher amounts of gillnet fishing effort. Areas of sand extraction prospection and offshore windfarms under construction should not overlap with hotspots of EP, at the exception of the sole spawning ground and the commercial species diversity hotspots. Finally, we highlight an overlap of more than 20% of four EP hotspots with Natura 2000 areas, while the Marine Natural Park in the South covers more EP coldspots (i.e. hake nursery, encounter rate, trophic links diversity) than hotspots.DiscussionIncorporating such a multifunctional spatial approach with hotspots and coldspots opens new perspective for marine spatial planning, pointing out the potential strengths and weaknesses of areas currently defined or prioritized for future uses like conservation, sand extraction or emerging activities like offshore windfarms.
Influence of the fracture on the seepage stability of loess slopes
Authors: Li Hongru , Yang Min , Dang Tong 
Published: June 2023

The development of fractures in loess slopes often has a great influence on the stability of slopes. In this paper, taking the homogeneous slope model as an example, fractures with different distances and depths from the slope top angle are provided at the top of the slope. Firstly, the influence of single fracture location and depth on slope stability is analyzed, and after the most unfavorable location and depth of the fractures are determined, the influence of the slope top fractures on the slope seepage field and slope stability under the conditions with and without rainfall is studied secondly. The results show that with the increase of the distance from the fracture to the top angle of the slope, the safety coefficient of the slope shows the change law of decreasing first and then increasing. The critical fracture depth corresponding to the fractures at different locations is different, and when the critical fracture depth is exceeded, the slope safety factor tends to be stable. At the end of the rainfall moment through 1-1 section to analyze, it is found that at this time the pore water pressure and volume water content of the soil at the bottom of the fracture at different depths are greater than those of the upper soil, and the shallow fracture has less influence on the seepage field of the slope, and through 2-2 section it is found that the pore water pressure and volume water content in the soil far from the fracture are greater than those of the soil near the location of the fracture. When 288 h after the end of rainfall, the pore water pressure and volumetric water content of the soil around the fracture in section 2-2 were greater than those far from the fracture location. With the passage of time, the pore water pressure at the location of the fracture gradually dissipated and the corresponding volumetric water content gradually decreased, indicating that the fracture had an obvious influence on the characteristics of the seepage field in the soil at different times of rainfall. Under the condition of no rainfall, there exists a critical depth of fractures affecting slope safety stability, while under the condition of rainfall, the slope safety coefficient continuously decreases with the increase of fracture depth, and there is no critical fracture depth. The research results promote the understanding of the safety and stability of loess fracture slopes and provide a reference for slope management.
The lactate dehydrogenase gene is involved in the growth and metabolism of Lacticaseibacillus paracasei and the production of fermented milk flavor substances
Authors: Fang Sichang , Song Xin , Cui Liru , Bai Jinping , Lu Han , Wang Shijie 
Published: June 2023

ObjectiveLactate dehydrogenase (ldh) in lactic acid bacteria is an important enzyme that is involved in the process of milk fermentation. This study aimed to explore the changes and effects of fermented milk metabolites in mutant strains after knocking out the ldh gene of Lacticaseibacillus paracasei.MethodsThe ldh mutant ΔAF91_07315 was obtained from L. paracasei using clustered regularly interspaced short palindromic repeats technology, and we determined fermented milk pH, titratable acidity, viable count, and differential metabolites in the different stages of milk fermentation that were identified using metabolomic analysis.ResultsThe results showed that the growth rate and acidification ability of the mutant strain were lower than those of the wild-type strain before the end of fermentation, and analysis of the differential metabolites showed that lactate, L-cysteine, proline, and intermediate metabolites of phenylalanine, tryptophan, and methionine were downregulated (P &lt; 0.05), which affected the growth initiation rate and acidification ability of the strain. At the end of fermentation (pH 4.5), the fermentation time of the mutant strain was prolonged and all differential metabolites were upregulated (P &lt; 0.05), including amino acids and precursors, acetyl coenzyme A, and other metabolites involved in amino acid and fatty acid synthesis, which are associated with the regulation of fermented milk flavors. In addition, riboflavin was upregulated to promote the growth of the strain and compensate for the growth defects caused by the mutation.ConclusionOur data established a link between the AF91_07315 gene and strain growth and metabolism and provided a target for the regulation of fermented milk flavor substances.
Pooled analysis of frontal lobe transcriptomic data identifies key mitophagy gene changes in Alzheimer's disease brain
Authors: Mei Taoyu , Li Yuan , Orduña Dolado Anna , Li Zhiquan , Andersson Robin , Berliocchi Laura , Rasmussen Lene Juel 
Published: June 2023

BackgroundThe growing prevalence of Alzheimer's disease (AD) is becoming a global health challenge without effective treatments. Defective mitochondrial function and mitophagy have recently been suggested as etiological factors in AD, in association with abnormalities in components of the autophagic machinery like lysosomes and phagosomes. Several large transcriptomic studies have been performed on different brain regions from AD and healthy patients, and their data represent a vast source of important information that can be utilized to understand this condition. However, large integration analyses of these publicly available data, such as AD RNA-Seq data, are still missing. In addition, large-scale focused analysis on mitophagy, which seems to be relevant for the aetiology of the disease, has not yet been performed.MethodsIn this study, publicly available raw RNA-Seq data generated from healthy control and sporadic AD post-mortem human samples of the brain frontal lobe were collected and integrated. Sex-specific differential expression analysis was performed on the combined data set after batch effect correction. From the resulting set of differentially expressed genes, candidate mitophagy-related genes were identified based on their known functional roles in mitophagy, the lysosome, or the phagosome, followed by Protein-Protein Interaction (PPI) and microRNA-mRNA network analysis. The expression changes of candidate genes were further validated in human skin fibroblast and induced pluripotent stem cells (iPSCs)-derived cortical neurons from AD patients and matching healthy controls.ResultsFrom a large dataset (AD: 589; control: 246) based on three different datasets (i.e., ROSMAP, MSBB, &amp; GSE110731), we identified 299 candidate mitophagy-related differentially expressed genes (DEG) in sporadic AD patients (male: 195, female: 188). Among these, the AAA ATPase VCP, the GTPase ARF1, the autophagic vesicle forming protein GABARAPL1 and the cytoskeleton protein actin beta ACTB were selected based on network degrees and existing literature. Changes in their expression were further validated in AD-relevant human in vitro models, which confirmed their down-regulation in AD conditions.ConclusionThrough the joint analysis of multiple publicly available data sets, we identify four differentially expressed key mitophagy-related genes potentially relevant for the pathogenesis of sporadic AD. Changes in expression of these four genes were validated using two AD-relevant human in vitro models, primary human fibroblasts and iPSC-derived neurons. Our results provide foundation for further investigation of these genes as potential biomarkers or disease-modifying pharmacological targets.