bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of pyroptosis-associated genes with diagnostic value in calcific aortic valve disease
Authors: Yu Chenxi , Zhang Yifeng , Yang Ling , Aikebaier Mirenuer , Shan Shuyao , Zha Qing , Yang Ke 
Published: January 2024

BackgroundCalcific aortic valve disease (CAVD) is one of the most prevalent valvular diseases and is the second most common cause for cardiac surgery. However, the mechanism of CAVD remains unclear. This study aimed to investigate the role of pyroptosis-related genes in CAVD by performing comprehensive bioinformatics analysis.MethodsThree microarray datasets (GSE51472, GSE12644 and GSE83453) and one RNA sequencing dataset (GSE153555) were obtained from the Gene Expression Omnibus (GEO) database. Pyroptosis-related differentially expressed genes (DEGs) were identified between the calcified and the normal valve samples. LASSO regression and random forest (RF) machine learning analyses were performed to identify pyroptosis-related DEGs with diagnostic value. A diagnostic model was constructed with the diagnostic candidate pyroptosis-related DEGs. Receiver operating characteristic (ROC) curve analysis was performed to estimate the diagnostic performances of the diagnostic model and the individual diagnostic candidate genes in the training and validation cohorts. CIBERSORT analysis was performed to estimate the differences in the infiltration of the immune cell types. Pearson correlation analysis was used to investigate associations between the diagnostic biomarkers and the immune cell types. Immunohistochemistry was used to validate protein concentration.ResultsWe identified 805 DEGs, including 319 down-regulated genes and 486 up-regulated genes. These DEGs were mainly enriched in pathways related to the inflammatory responses. Subsequently, we identified 17 pyroptosis-related DEGs by comparing the 805 DEGs with the 223 pyroptosis-related genes. LASSO regression and RF algorithm analyses identified three CAVD diagnostic candidate genes (TREM1, TNFRSF11B, and PGF), which were significantly upregulated in the CAVD tissue samples. A diagnostic model was constructed with these 3 diagnostic candidate genes. The diagnostic model and the 3 diagnostic candidate genes showed good diagnostic performances with AUC values &gt;0.75 in both the training and the validation cohorts based on the ROC curve analyses. CIBERSORT analyses demonstrated positive correlation between the proportion of M0 macrophages in the valve tissues and the expression levels of TREM1, TNFRSF11B, and PGF.ConclusionThree pyroptosis-related genes (TREM1, TNFRSF11B and PGF) were identified as diagnostic biomarkers for CAVD. These pyroptosis genes and the pro-inflammatory microenvironment in the calcified valve tissues are potential therapeutic targets for alleviating CAVD.
Profiling endogenous adrenal function during veno-venous ECMO support in COVID-19 ARDS: a descriptive analysis
Authors: Baumgartner Clemens , Wolf Peter , Hermann Alexander , König Sebastian , Maleczek Mathias , Laxar Daniel , Poglitsch Marko , Domenig Oliver , Krenn Katharina , Schiefer Judith , Kautzky-Willer Alexandra , Krebs Michael , Hermann Martina 
Published: January 2024

BackgroundProlonged critical illness is often accompanied by an impairment of adrenal function, which has been frequently related to conditions complicating patient management. The presumed connection between hypoxia and the pathogenesis of this critical- illness- related corticosteroid insufficiency (CIRCI) might play an important role in patients with severe acute respiratory distress syndrome (ARDS). Since extracorporeal membrane oxygenation (ECMO) is frequently used in ARDS, but data on CIRCI during this condition are scarce, this study reports the behaviour of adrenal function parameters during oxygenation support with veno-venous (vv)ECMO in coronavirus disease 2019 (COVID-19) ARDS.MethodsA total of 11 patients undergoing vvECMO due to COVID-19 ARDS at the Medical University of Vienna, who received no concurrent corticosteroid therapy, were retrospectively included in this study. We analysed the concentrations of cortisol, aldosterone, and angiotensin (Ang) metabolites (Ang I–IV, Ang 1–7, and Ang 1–5) in serum via liquid chromatography/tandem mass spectrometry before, after 1 day, 1 week, and 2 weeks during vvECMO support and conducted correlation analyses between cortisol and parameters of disease severity.ResultsCortisol concentrations appeared to be lowest after initiation of ECMO and progressively increased throughout the study period. Higher concentrations were related to disease severity and correlated markedly with interleukin-6, procalcitonin, pH, base excess, and albumin during the first day of ECMO. Fair correlations during the first day could be observed with calcium, duration of critical illness, and ECMO gas flow. Angiotensin metabolite concentrations were available in a subset of patients and indicated a more homogenous aldosterone response to plasma renin activity after 1 week of ECMO support.ConclusionOxygenation support through vvECMO may lead to a partial recovery of adrenal function over time. In homogenous patient collectives, this novel approach might help to further determine the importance of adrenal stress response in ECMO and the influence of oxygenation support on CIRCI.
A mutual comparison of pregnancy outcomes between different conception modes: a propensity score matching based retrospective cohort study
Authors: Sun Chang-Fa , Sheng Jian-Zhong , Huang He-Feng 
Published: January 2024

BackgroundAssisted reproductive technology (ART) has been reported to have negative effects on maternal and neonatal health. Ovulation induction (OI) was reported to be associated with alteration of epigenetic modification of mice embryos, and extinguishing the influence of ovulation induction and in vitro operations on maternal and neonatal health will bring benefits for reducing side effects. The present study aimed to determine whether ovulation induction alone and ART are associated with adverse pregnancy outcomes and whether ART could induce a higher risk than ovulation induction alone.MethodsA total of 51,172 cases with singleton live birth between Jan 2016 and May 2019 at the International Peace Maternal and Child Health Hospital were included in this study. Conception modes documented during registration were classified into natural conception (NC), OI, and ART. Pregnancy outcomes of the three groups with balanced baseline characteristics by propensity score matching were compared. The relative risks of maternal and neonatal outcomes were calculated by logistic regression analysis.ResultsCompared with natural conception, infertility treatments are associated with gestational diabetes (OI: OR 1.72, 95% CI 1.31-2.27; ART: OR 1.67, 95% CI 1.26-2.20), preeclampsia/eclampsia (OI: OR 1.86, 95% CI 1.03-3.36; ART: OR 2.23, 95% CI 1.26-3.92). Even if gestational diabetes, gestational hypertension, and placental problems were adjusted, infertility treatments are associated with birth before 37 weeks (OI: OR 1.99, 95% CI 1.28-3.12; ART: OR 1.70, 95% CI 1.08-2.69), low birth weight (OI: OR 2.19, 95% CI 1.23-3.91; ART: OR 1.90, 95% CI 1.05-3.45), and SGA (OI: OR 2.42, 95% CI 1.20-4.87; ART: OR 2.56, 95% CI 1.28-5.11). ART but not OI is associated with a higher risk of birth before 34 weeks (OR:3.12, 95% CI 1.21-8.05). By comparing the OI group with the ART group, we only found that ART could induce a higher ratio of placental problems (5.0%, 26/518 vs 2.1%, 11/519, p&lt;0.05).ConclusionBoth OI and ART are associated with adverse pregnancy outcomes. ART induced comparable negative effects with OI on gestational complications, birth weight, and premature birth (&lt;37 weeks). However, ART resulted in a higher risk of placental problems than group NC and OI. The incidence of birth before 34 weeks of gestation in the ART group tends to be higher than in the OI group, but not statistically significant. The side effects of ART may originate from OI.
Diversity and distribution patterns of soil macroarthropod communities in the Nianchu River Basin, Tibet, China
Authors: Wang Zhuang-Zhuang , Zhang Peng , He Kai , Zhu Shi-Ying , Pu Bu 
Published: January 2024

IntroductionThe study of how soil fauna interact with soil ecosystems is an important research field. At present, there has been little research on the diversity and distribution patterns of soil macroarthropods and on the relationship between soil fauna and environmental factors in Tibet.MethodsThe data collection for soil macroarthropods and soil samples was conducted using the plum blossom five-point sampling method. Subsequently, the gathered data were meticulously organized and analyzed through a blend of ecological and statistical approaches.ResultsIn total, 2880 soil macroarthropods were captured from 19 plots in the Nianchu River Basin, and the soil macroarthropod Hill numbers was at its lowest in spring. Sea buckthorn forest habitats had the highest Hill numbers. We found that Carabidae, Lycosidae, and Formicidae were always dominant species during seasonal changes in the Nianchu River Basin. Among the four different habitat types studied, Carabidae always appeared across the four studied habitat types and was one of the most significant taxa. The niche range of soil macroarthropods was wetland habitat &gt; farmland habitat &gt; sea buckthorn forest habitat &gt; grassland habitat, and their community within sea buckthorn forest habitats was stable. The niche breadth of soil macroarthropods was the largest in summer, and the community was stable. Soil temperature and soil water content were the most important factors affecting the alpha diversity of soil macroarthropods, while altitude and soil temperature were the most important factors affecting their beta diversity.DiscussionIn summary, the results provide a comprehensive overview of the seasonal and habitat dynamics of soil macroarthropods in the Nianchu River Basin; it is strongly believed that the research carried out in this paper can contribute valuable information toward further research on the soil fauna diversity and ecological functions in this area and provide a strong scientific basis for the protection and sustainable development of the Nianchu River Basin ecosystem.
Investigating the shared genetic architecture between hypothyroidism and rheumatoid arthritis
Authors: Peng Zhifang , Huang Weiping , Tang Mengjun , Chen Binbin , Yang Renqi , Liu Qing , Liu Chaoshui , Long Panpan 
Published: January 2024

BackgroundThere is still controversy regarding the relationship between hypothyroidism and rheumatoid arthritis (RA), and there has been a dearth of studies on this association. The purpose of our study was to explore the shared genetic architecture between hypothyroidism and RA.MethodsUsing public genome-wide association studies summary statistics of hypothyroidism and RA, we explored shared genetics between hypothyroidism and RA using linkage disequilibrium score regression, ρ-HESS, Pleiotropic analysis under a composite null hypothesis (PLACO), colocalization analysis, Multi-Trait Analysis of GWAS (MTAG), and transcriptome-wide association study (TWAS), and investigated causal associations using Mendelian randomization (MR).ResultsWe found a positive genetic association between hypothyroidism and RA, particularly in local genomic regions. Mendelian randomization analysis suggested a potential causal association of hypothyroidism with RA. Incorporating gene expression data, we observed that the genetic associations between hypothyroidism and RA were enriched in various tissues, including the spleen, lung, small intestine, adipose visceral, and blood. A comprehensive approach integrating PLACO, Bayesian colocalization analysis, MTAG, and TWAS, we successfully identified TYK2, IL2RA, and IRF5 as shared risk genes for both hypothyroidism and RA.ConclusionsOur investigation unveiled a shared genetic architecture between these two diseases, providing novel insights into the underlying biological mechanisms and establishing a foundation for more effective interventions.
Elucidating common pathogenic transcriptional networks in infective endocarditis and sepsis: integrated insights from biomarker discovery and single-cell RNA sequencing
Authors: Yi Chen , Zhang Haoxiang , Yang Jun , Chen Dongjuan , Jiang Shaofeng 
Published: January 2024

BackgroundInfective Endocarditis (IE) and Sepsis are two closely related infectious diseases, yet their shared pathogenic mechanisms at the transcriptional level remain unclear. This research gap poses a barrier to the development of refined therapeutic strategies and drug innovation.MethodsThis study employed a collaborative approach using both microarray data and single-cell RNA sequencing (scRNA-seq) data to identify biomarkers for IE and Sepsis. It also offered an in-depth analysis of the roles and regulatory patterns of immune cells in these diseases.ResultsWe successfully identified four key biomarkers correlated with IE and Sepsis, namely CD177, IRAK3, RNASE2, and S100A12. Further investigation revealed the central role of Th1 cells, B cells, T cells, and IL-10, among other immune cells and cytokines, in the pathogenesis of these conditions. Notably, the small molecule drug Matrine exhibited potential therapeutic effects by targeting IL-10. Additionally, we discovered two Sepsis subgroups with distinct inflammatory responses and therapeutic strategies, where CD177 demonstrated significant classification value. The reliability of CD177 as a biomarker was further validated through qRT-PCR experiments.ConclusionThis research not only paves the way for early diagnosis and treatment of IE and Sepsis but also underscores the importance of identifying shared pathogenic mechanisms and novel therapeutic targets at the transcriptional level. Despite limitations in data volume and experimental validation, these preliminary findings add new perspectives to our understanding of these complex diseases.
Predictive value of hyponatremia for short-term mortality in supratentorial spontaneous intracerebral hemorrhage: a single center study
Authors: Qian Ao , Zheng Longyi , He Zeyuan , Zhou Jing , Tang Shuang , Xing Wenli 
Published: January 2024

BackgroundHyponatremia is a common electrolyte disturbance in patients with neurological disease; however, its predictive role for outcome in patients with supratentorial spontaneous intracerebral hemorrhage (sICH) is controversial. This study aims to explore the association between hyponatremia within 7 days after bleeding and 90-day mortality in patients with supratentorial sICH.MethodsA retrospective analysis was conducted at our institution. Patients with sICH meeting the inclusion criteria were enrolled in this study. Multivariate regression analyses were performed to determine the predictive value of hyponatremia (serum sodium &lt;135 mmol/L) for 90-day mortality and functional outcome. Subgroup analysis was performed based on the degree and duration of hyponatremia and therapeutic strategies. The Spearman correlation test was performed to explore the relationship between hyponatremia severity and duration with variables in a multivariate regression model. Kaplan–Meier curve was depicted to reveal the relationship between hyponatremia and mortality. The receiver operating characteristic (ROC) curve was plotted to show the diagnostic effect of the minimum concentration of serum sodium (sodiummin) on 90-day mortality.ResultsA total of 960 patients were enrolled, 19.6% (188) of whom were patients with hyponatremia and 26.0% (250) had 90-day mortality. The incidence of hyponatremia was roughly 2.5 times in non-survivors compared with survivors (34.8% vs. 14.2%). Multivariate regression analysis revealed that hyponatremia was the independent predictor of 90-day mortality (OR 2.763, 95%CI 1.836–4.157) and adverse outcome (OR 3.579, 95%CI 2.332–6.780). Subgroup analysis indicated an increased trend in mortality risk with both duration (more or less than 48 h) and severity of hyponatremia (mild, moderate, and severe) and confirmed the predictive value of hyponatremia for mortality in patients undergoing surgical intervention (external ventricular drainage, craniotomy, and decompressive craniectomy; all p &lt; 0.05). The Spearman correlation test indicated no moderate or strong relationship between hyponatremia severity and duration with other variables in the multivariate model (all |rs| &lt; 0.4). The ROC curve suggested the moderate diagnostic performance of sodiummin for mortality in both general patients and subgroups of therapeutic method patients (AUC from 0.6475 to 0.7384).ConclusionHyponatremia occurring in the first 7 days after bleeding is an independent predictor of 90-day morality and adverse outcome. Rigorous electrolyte scrutiny in patients treated surgically is required.
A generalizable deep voxel-guided morphometry algorithm for the detection of subtle lesion dynamics in multiple sclerosis
Authors: Raj Anish , Gass Achim , Eisele Philipp , Dabringhaus Andreas , Kraemer Matthias , Zöllner Frank G. 
Published: January 2024

IntroductionMultiple sclerosis (MS) is a chronic neurological disorder characterized by the progressive loss of myelin and axonal structures in the central nervous system. Accurate detection and monitoring of MS-related changes in brain structures are crucial for disease management and treatment evaluation. We propose a deep learning algorithm for creating Voxel-Guided Morphometry (VGM) maps from longitudinal MRI brain volumes for analyzing MS disease activity. Our approach focuses on developing a generalizable model that can effectively be applied to unseen datasets.MethodsLongitudinal MS patient high-resolution 3D T1-weighted follow-up imaging from three different MRI systems were analyzed. We employed a 3D residual U-Net architecture with attention mechanisms. The U-Net serves as the backbone, enabling spatial feature extraction from MRI volumes. Attention mechanisms are integrated to enhance the model's ability to capture relevant information and highlight salient regions. Furthermore, we incorporate image normalization by histogram matching and resampling techniques to improve the networks' ability to generalize to unseen datasets from different MRI systems across imaging centers. This ensures robust performance across diverse data sources.ResultsNumerous experiments were conducted using a dataset of 71 longitudinal MRI brain volumes of MS patients. Our approach demonstrated a significant improvement of 4.3% in mean absolute error (MAE) against the state-of-the-art (SOTA) method. Furthermore, the algorithm's generalizability was evaluated on two unseen datasets (n = 116) with an average improvement of 4.2% in MAE over the SOTA approach.DiscussionResults confirm that the proposed approach is fast and robust and has the potential for broader clinical applicability.
Identification of a novel RPGR mutation associated with retinitis pigmentosa and primary ciliary dyskinesia in a Slovak family: a case report
Authors: Kolkova Zuzana , Durdik Peter , Holubekova Veronika , Durdikova Anna , Jesenak Milos , Banovcin Peter 
Published: January 2024

BackgroundThe mutations in the RPGR (retinitis pigmentosa GTPase regulator) gene are the most common cause of X-linked retinitis pigmentosa (XLRP), a rare genetic disorder affecting the photoreceptor cells in the retina. Several reported cases identified this gene as a genetic link between retinitis pigmentosa (RP) and primary ciliary dyskinesia (PCD), characterised by impaired ciliary function predominantly in the respiratory tract. Since different mutations in the same gene can result in various clinical manifestations, it is important to describe a correlation between the gene variant and the observed phenotype.MethodsTwo young brothers from a non-consanguineous Slovak family with diagnosed retinal dystrophy and recurrent respiratory infections were examined. Suspected PCD was diagnosed based on a PICADAR questionnaire, nasal nitric oxide analysis, transmission electron microscopy, high-speed video microscopy analysis, and genetic testing.ResultsWe identified a novel frameshift RPGR mutation NM_001034853: c.309_310insA, p.Glu104Argfs*12, resulting in a complex X-linked phenotype combining PCD and RP. In our patients, this mutation was associated with normal ultrastructure of respiratory cilia, reduced ciliary epithelium, more aciliary respiratory epithelium, shorter cilia, and uncoordinated beating with a frequency at a lower limit of normal beating, explaining the clinical manifestation of PCD in our patients.ConclusionThe identified novel pathogenic mutation in the RPGR gene expands the spectrum of genetic variants associated with the X-linked PCD phenotype overlapping with RP, highlighting the diversity of mutations contributing to the disorder. The described genotype–phenotype correlation can be useful in clinical practice to recognise a broader spectrum of PCD phenotypes as well as for future research focused on the genetic basis of PCD, gene interactions, the pathways implicated in PCD pathogenesis, and the role of RPGR protein for the proper functioning of cilia in various tissues throughout the body.
Characterization of active peptides derived from three leeches and comparison of their anti-thrombotic mechanisms using the tail vein thrombosis model in mice and metabonomics
Authors: Dong Weichao , Li Huajian , Li Yanan , Wang Yuqing , Dai Long , Wang Shaoping 
Published: January 2024

Background and aims: The increasing incidence of cardiovascular diseases has created an urgent need for safe and effective anti-thrombotic agents. Leech, as a traditional Chinese medicine, has the effect of promoting blood circulation and removing blood stasis, but its real material basis and mechanism of action for the treatment of diseases such as blood stasis and thrombosis have not been reported.Methods: In this study, Whitmania Pigra Whitman (WPW), Hirudo nipponica Whitman (HNW) and Whitmania acranutata Whitman (WAW) were hydrolyzed by biomimetic enzymatic hydrolysis to obtain the active peptides of WPW (APP), the active peptides of HNW (APH) and the active peptides of WAW (APA), respectively. Then their structures were characterized by sykam amino acid analyzer, fourier transform infrared spectrometer (FT-IR), circular dichroism (CD) spectrometer and LC-MS. Next, the anti-thrombotic activities of APP, APH and APA were determined by carrageenan-induced tail vein thrombosis model in mice, and the anti-thrombotic mechanisms of high-dose APP group (HAPP), high-dose APH group (HAPH) and high-dose APA group (HAPA) were explored based on UHPLC-Q-Exactive Orbitrap mass spectrometry.Results: The results showed that the amino acid composition of APP, APH and APA was consistent, and the proportion of each amino acid was few different. The results of FT-IR and CD showed that there were no significant differences in the proportion of secondary structures (such as β-sheet and random coil) and infrared absorption peaks between APP, APH and APA. Mass spectrometry data showed that there were 43 common peptides in APP, APH and APA, indicating that the three have common material basis. APP, APH and APA could significantly inhibit platelet aggregation, reduce black-tail length, whole blood viscosity (WBV), plasma viscosity (PV), and Fibrinogen (FIB), and prolong coagulation time, including activated partial thrombin time (APTT), prothrombin time (PT) and thrombin time (TT). In addition, 24 metabolites were identified as potential biomarkers associated with thrombosis development. Among these, 19, 23, and 20 metabolites were significantly normalized after administration of HAPP, HAPH, and HAPA in the mice, respectively. Furthermore, the intervention mechanism of HAPP, HAPH and HAPA on tail vein thrombosis mainly involved in linoleic acid metabolism, primary bile acid biosynthesis and ether lipid metabolism.Conclusion: Our findings suggest that APP, APH and APA can exert their anti-blood stasis and anti-thrombotic activities by interfering with disordered metabolic pathways in vivo, and there is no significant difference in their efficacies.