bluuebunny/crossref_metadata_2025_split huggingface dataset:
Source cell-type epigenetic memory persists in induced pluripotent cells but is lost in subsequently derived germline cells
Authors: Lin Yu-Huey , Lehle Jake D. , McCarrey John R. 
Published: February 2024

Introduction: Retention of source cell-type epigenetic memory may mitigate the potential for induced pluripotent stem cells (iPSCs) to fully achieve transitions in cell fate in vitro. While this may not preclude the use of iPSC-derived somatic cell types for therapeutic applications, it becomes a major concern impacting the potential use of iPSC-derived germline cell types for reproductive applications. The transition from a source somatic cell type to iPSCs and then on to germ-cell like cells (GCLCs) recapitulates two major epigenetic reprogramming events that normally occur during development in vivo—embryonic reprogramming in the epiblast and germline reprogramming in primordial germ cells (PGCs). We examined the extent of epigenetic and transcriptomic memory persisting first during the transition from differentiated source cell types to iPSCs, and then during the transition from iPSCs to PGC-like cells (PGCLCs).Methods: We derived iPSCs from four differentiated mouse cell types including two somatic and two germ cell types and tested the extent to which each resulting iPSC line resembled a) a validated ES cell reference line, and b) their respective source cell types, on the basis of genome-wide gene expression and DNA methylation patterns. We then induced each iPSC line to form PGCLCs, and assessed epigenomic and transcriptomic memory in each compared to endogenous PGCs/M-prospermatogonia.Results: In each iPSC line, we found residual gene expression and epigenetic programming patterns characteristic of the corresponding source differentiated cell type from which each was derived. However, upon deriving PGCLCs, we found very little evidence of lingering epigenetic or transcriptomic memory of the original source cell type.Discussion: This result indicates that derivation of iPSCs and then GCLCs from differentiated source cell types in vitro recapitulates the two-phase epigenetic reprogramming that normally occurs in vivo, and that, to a significant extent, germline cell types derived in vitro from pluripotent cells accurately recapitulate epigenetic programming and gene expression patterns corresponding to equivalent endogenous germ cell types, suggesting that they have the potential to form the basis of in vitro gametogenesis as a useful therapeutic strategy for treatment of infertility.
Clinical assessment to identify pelvic injuries in the prehospital setting: a prospective cohort study
Authors: Coulombe Pascale , Robitaille-Fortin Maxime , Nadeau Alexandra , Malo Christian , Blanchard Pierre-Gilles , Benhamed Axel , Émond Marcel , Mercier Eric 
Published: February 2024

ObjectivesPelvic injuries can be life-threatening and are challenging to identify in the prehospital phase. This study aimed to assess how pelvic examination is performed by paramedics and to determine the accuracy of their clinical examination when identifying pelvic fractures.MethodsThis was a prospective cohort study of prehospital interventions including both real and simulated trauma patients between July and August 2022. Data collection for the injured patient was made by an observer who was paired with teams of two consenting paramedics. Data pertaining to the clinical assessment for potential pelvic injuries during all interventions with a trauma patient were collected. Additionally, data were collected during four simulated scenarios of patients with an open-book type pelvic fracture following high-energy trauma mechanisms.ResultsA total of 29 trauma-related clinical interventions were assessed. Most patients were female (n = 22, 75.9%) with a mean age of 69.8 (SD 22.2) years. Fall from standing was the main trauma mechanism (n = 21, 72.4%). During 72.4% (n = 21) of all trauma-related interventions, an assessment for pelvic injuries was performed, mostly by pelvic palpation (n = 19, 65.5%), inquiring about the presence of pain (n = 12, 41.4%), searching for deformation (n = 7, 24.1%), and/or assessing leg length (n = 8, 27.6%). No pelvic injury was suspected by the paramedics, but two patients (6.9%) had a pelvic fracture and two (6.9%) had a hip fracture. Simulated cases of high-velocity mechanisms with an open-book pelvic fracture were completed by 11 pairs of paramedics. Most did a clinical pelvic assessment (n = 8, 72.7%) using palpation. When asked after the simulation, nine pairs (81.8%) suspected a pelvic fracture.ConclusionPelvic injuries are challenging to identify, and pelvic assessment on the field is not standardized among paramedics. Training is needed to increase awareness relative to pelvic injuries and to improve detection.
Non-linear associations of cardiometabolic index with insulin resistance, impaired fasting glucose, and type 2 diabetes among US adults: a cross-sectional study
Authors: Song Jimei , Li Yimei , Zhu Junxia , Liang Jian , Xue Shan , Zhu Zhangzhi 
Published: February 2024

BackgroundCardiometabolic index (CMI) is a novel indicator for predicting the risk of obesity-related diseases. We aimed to determine the relationships of CMI with insulin resistance (IR), impaired fasting glucose (IFG), and type 2 diabetes mellitus (T2DM) using NHANES data from 1999 to 2020.MethodsAfter CMI values were estimated, weighted univariate and multivariate logistic regression analyses were used to ascertain whether CMI was an independent risk indicator for IR, IFG, and T2DM. Furthermore, stratified analyses and interaction analyses were carried out to investigate the heterogeneity of correlations across various subgroups. Subsequently, restricted cubic splines (RCS) were used to examine nonlinear relationships.Results21,304 US adults were enrolled in our study, of whom 5,326 (22.38%) had IR, 4,706 (20.17%) had IFG, and 3,724 (13.02%) had T2DM. In the studied population, a higher CMI index value was significantly associated with an elevated likelihood of IR, IFG, and T2DM. In the RCS regression model, the relationship between CMI and IR, IFG, and T2DM was identified as nonlinear. A nonlinear inverted U-shaped relationship was found between CMI and IFG, and an inverse L-shaped association was observed between CMI and IR, CMI and T2DM. The cut-off values of CMI were 1.35, 1.48, and 1.30 for IR, IFG, and T2DM, respectively.ConclusionOur results indicate that CMI was positively correlated with an increase in IR, IFG, and T2DM in the studied population. CMI may be a simple and effective surrogate indicator of IR, IFG, and T2DM.
Identification of a gene network driving the attenuated response to lipopolysaccharide of monocytes from hypertensive coronary artery disease patients
Authors: Lu Chang , Donners Marjo M. P. C. , de Baaij Julius B. J. , Jin Han , Otten Jeroen J. T. , Manca Marco , van Zonneveld Anton Jan , Jukema J. Wouter , Kraaijeveld Adriaan , Kuiper Johan , Pasterkamp Gerard , Mees Barend , Sluimer Judith C. , Cavill Rachel , Karel Joël M. H. , Goossens Pieter , Biessen Erik A. L. 
Published: February 2024

IntroductionThe impact of cardiovascular disease (CVD) risk factors, encompassing various biological determinants and unhealthy lifestyles, on the functional dynamics of circulating monocytes—a pivotal cell type in CVD pathophysiology remains elusive. In this study, we aimed to elucidate the influence of CVD risk factors on monocyte transcriptional responses to an infectious stimulus.MethodsWe conducted a comparative analysis of monocyte gene expression profiles from the CTMM – CIRCULATING CELLS Cohort of coronary artery disease (CAD) patients, at baseline and after lipopolysaccharide (LPS) stimulation. Gene co-expression analysis was used to identify gene modules and their correlations with CVD risk factors, while pivotal transcription factors controlling the hub genes in these modules were identified by regulatory network analyses. The identified gene module was subjected to a drug repurposing screen, utilizing the LINCS L1000 database.ResultsMonocyte responsiveness to LPS showed a highly significant, negative correlation with blood pressure levels (ρ&lt; -0.4; P&lt;10-80). We identified a ZNF12/ZBTB43-driven gene module closely linked to diastolic blood pressure, suggesting that monocyte responses to infectious stimuli, such as LPS, are attenuated in CAD patients with elevated diastolic blood pressure. This attenuation appears associated with a dampening of the LPS-induced suppression of oxidative phosphorylation. Finally, we identified the serine-threonine inhibitor MW-STK33-97 as a drug candidate capable of reversing this aberrant LPS response. ConclusionsMonocyte responses to infectious stimuli may be hampered in CAD patients with high diastolic blood pressure and this attenuated inflammatory response may be reversed by the serine-threonine inhibitor MW-STK33-97. Whether the identified gene module is a mere indicator of, or causal factor in diastolic blood pressure and the associated dampened LPS responses remains to be determined.
Identification of cuproptosis-related gene clusters and immune cell infiltration in major burns based on machine learning models and experimental validation
Authors: Wang Xin , Xiong Zhenfang , Hong Wangbing , Liao Xincheng , Yang Guangping , Jiang Zhengying , Jing Lanxin , Huang Shengyu , Fu Zhonghua , Zhu Feng 
Published: February 2024

IntroductionBurns are a global public health problem. Major burns can stimulate the body to enter a stress state, thereby increasing the risk of infection and adversely affecting the patient’s prognosis. Recently, it has been discovered that cuproptosis, a form of cell death, is associated with various diseases. Our research aims to explore the molecular clusters associated with cuproptosis in major burns and construct predictive models.MethodsWe analyzed the expression and immune infiltration characteristics of cuproptosis-related factors in major burn based on the GSE37069 dataset. Using 553 samples from major burn patients, we explored the molecular clusters based on cuproptosis-related genes and their associated immune cell infiltrates. The WGCNA was utilized to identify cluster-specific genes. Subsequently, the performance of different machine learning models was compared to select the optimal model. The effectiveness of the predictive model was validated using Nomogram, calibration curves, decision curves, and an external dataset. Finally, five core genes related to cuproptosis and major burn have been was validated using RT-qPCR.ResultsIn both major burn and normal samples, we determined the cuproptosis-related genes associated with major burns through WGCNA analysis. Through immune infiltrate profiling analysis, we found significant immune differences between different clusters. When K=2, the clustering number is the most stable. GSVA analysis shows that specific genes in cluster 2 are closely associated with various functions. After identifying the cross-core genes, machine learning models indicate that generalized linear models have better accuracy. Ultimately, a generalized linear model for five highly correlated genes was constructed, and validation with an external dataset showed an AUC of 0.982. The accuracy of the model was further verified through calibration curves, decision curves, and modal graphs. Further analysis of clinical relevance revealed that these correlated genes were closely related to time of injury.ConclusionThis study has revealed the intricate relationship between cuproptosis and major burns. Research has identified 15 cuproptosis-related genes that are associated with major burn. Through a machine learning model, five core genes related to cuproptosis and major burn have been selected and validated.
Independent associations of education, intelligence, and cognition with gastrointestinal diseases and the mediating effects of risk factors: a Mendelian randomization study
Authors: Gu Mingyu , Wen Minghai , Wu Di , Xie Tianyu , Wang Xinxin 
Published: February 2024

BackgroundEducation, intelligence and cognition affect occupational performance and socioeconomic status and may influence virous diseases development. However, the impact of these factors on gastrointestinal diseases and their mediating risk factors remains unclear.MethodsWe utilized genome-wide association studies from European ancestry populations to perform two-sample Mendelian randomization analyses, aiming to estimate genetic instruments associated with education, intelligence, or cognition in relation to 24 gastrointestinal diseases Subsequently, we evaluated 14 potential mediators of this association and calculated the corresponding mediated proportions through two-step Mendelian randomization analyses.ResultAs the dominant factor in gastrointestinal diseases, education had a statistically significant association with 2 gastrointestinal diseases (acute pancreatitis, gastroesophageal reflux) and a suggestive association with 6 diseases (cirrhosis, alcoholic liver disease, cholecystitis, cholelithiasis, chronic gastritis and gastric ulcer). Of the 14 mediators, smoking and adiposity traits played a major role in mediating the effects.ConclusionThe study demonstrated the causal, independent impact of education on specific gastrointestinal diseases. Smoking and adiposity traits emerged as primary mediators, illuminating potential avenues for targeted interventions for prevention of them.
Exploring the causal relationship between gut microbiota and multiple myeloma risk based on Mendelian randomization and biological annotation
Authors: Feng Zuxi , Liao Minjing , Bai Jun , Li Yanhong , Chen Yue , Zhang Li , Guo Xuege , Li Lijuan , Zhang Liansheng 
Published: February 2024

IntroductionThe microbial genome-wide association studies (mbGWAS) have highlighted significant host-microbiome interactions based on microbiome heritability. However, establishing causal relationships between particular microbiota and multiple myeloma (MM) remains challenging due to limited sample sizes.MethodsGut microbiota data from a GWAS with 18,340 participants and MM summary statistics from 456,348 individuals. The inverse variance-weighted (IVW) method was used as the main bidirectional Mendelian randomization (MR) analysis. To assess the robustness of our results, we further performed supplementary analyses, including MR pleiotropy residual sum and outlier (MR-PRESSO) test, MR-Egger, Weighted median, Simple mode, and Weighted mode. Moreover, a backward MR analysis was conducted to investigate the potential for reverse causation. Finally, gene and gene-set-based analyses were then conducted to explore the common biological factors connecting gut microbiota and MM.ResultsWe discovered that 10 gut microbial taxa were causally related to MM risk. Among them, family Acidaminococcaceae, Bacteroidales family S24-7, family Porphyromonadaceae, genus Eubacterium ruminantium group, genus Parabacteroides, and genus Turicibacter were positively correlated with MM. Conversely, class Verrucomicrobia, family Verrucomicrobiaceae, genus Akkermansia, and order Verrucomicrobiales were negatively correlated with MM. The heterogeneity test revealed no Heterogeneity. MR-Egger and MR-PRESSO tests showed no significant horizontal pleiotropy. Importantly, leave-one-out analysis confirmed the robustness of MR results. In the backward MR analysis, no statistically significant associations were discovered between MM and 10 gut microbiota taxa. Lastly, we identified novel host-microbiome shared genes (AUTS2, CDK2, ERBB3, IKZF4, PMEL, SUOX, and RAB5B) that are associated with immunoregulation and prognosis in MM through biological annotation.DiscussionOverall, this study provides evidence supporting a potential causal relationship between gut microbiota and MM risk, while also revealing novel host-microbiome shared genes relevant to MM immunoregulation and clinical prognosis.
Unraveling the spatial–temporal distribution patterns of soil abundant and rare bacterial communities in China’s subtropical mountain forest
Authors: Wu Panpan , Hu Dandan , Guo Jiaheng , Li Jinlong , Zhong Quanlin , Cheng Dongliang 
Published: February 2024

IntroductionThe pivotal roles of both abundant and rare bacteria in ecosystem function are widely acknowledged. Despite this, the diversity elevational patterns of these two bacterial taxa in different seasons and influencing factors remains underexplored, especially in the case of rare bacteria.MethodsHere, a metabarcoding approach was employed to investigate elevational patterns of these two bacterial communities in different seasons and tested the roles of soil physico-chemical properties in structuring these abundant and rare bacterial community.Results and discussionOur findings revealed that variation in elevation and season exerted notably effects on the rare bacterial diversity. Despite the reactions of abundant and rare communities to the elevational gradient exhibited similarities during both summer and winter, distinct elevational patterns were observed in their respective diversity. Specifically, abundant bacterial diversity exhibited a roughly U-shaped pattern along the elevation gradient, while rare bacterial diversity increased with the elevational gradient. Soil moisture and N:P were the dominant factor leading to the pronounced divergence in elevational distributions in summer. Soil temperature and pH were the key factors in winter. The network analysis revealed the bacteria are better able to adapt to environmental fluctuations during the summer season. Additionally, compared to abundant bacteria, the taxonomy of rare bacteria displayed a higher degree of complexity. Our discovery contributes to advancing our comprehension of intricate dynamic diversity patterns in abundant and rare bacteria in the context of environmental gradients and seasonal fluctuations.
A comprehensive technology strategy for microbial identification and contamination investigation in the sterile drug manufacturing facility—a case study
Authors: Song Minghui , Li Qiongqiong , Liu Chengzhi , Wang Peien , Qin Feng , Zhang Lichun , Fan Yiling , Shao Hong , Chen Guiliang , Yang Meicheng 
Published: February 2024

ObjectiveA comprehensive strategy for microbial identification and contamination investigation during sterile drug manufacturing was innovatively established in this study, mainly based on MALDI-TOF MS for the identification and complemented by sequencing technology on strain typing.MethodsIt was implemented to monitor the bacterial contamination of a sterile drug manufacturing facility, including its bacterial distribution features and patterns. In three months, two hundred ninety-two samples were collected covering multiple critical components of raw materials, personnel, environment, and production water.ResultsBased on our strategy, the bacterial profile across the production process was determined: 241/292 bacterial identities were obtained, and Staphylococcus spp. (40.25%), Micrococcus spp.(11.20%), Bacillus spp. (8.30%), Actinobacteria (5.81%), and Paenibacillus spp. (4.56%) are shown to be the most dominant microbial contaminants. With 75.8% species-level and 95.4% genus-level identification capability, MALDI-TOF MS was promising to be a first-line tool for environmental monitoring routine. Furthermore, to determine the source of the most frequently occurring Staphylococcus cohnii, which evidenced a widespread presence in the entire process, a more discriminating S. cohnii whole-genome SNP typing method was developed to track the transmission routes. Phylogenetic analysis based on SNP results indicated critical environment contamination is highly relevant to personnel flow in this case. The strain typing results provide robust and accurate information for the following risk assessment step and support effective preventive and corrective measures.ConclusionIn general, the strategy presented in this research will facilitate the development of improved production and environmental control processes for the pharmaceutical industry, and give insights about how to provide more sound and reliable evidence for the optimization of its control program.
Feasibility and comparability of different platelet function tests in acute stroke with or without prior antiplatelet therapy
Authors: Schaefer Jan Hendrik , Lieschke Franziska , Urban Hans , Bohmann Ferdinand O. , Gatzke Florian , Miesbach Wolfgang 
Published: February 2024

BackgroundThe clinical course of ischemic and hemorrhagic strokes can be influenced by the coagulation status of individual patients. The prior use of antiplatelet therapy (APT) such as acetylsalicylic acid (ASA) or P2Y12-antagonists has been inconsistently described as possibly increasing the risk of hemorrhagic transformation or expansion. Since clinical studies describing prior use of antiplatelet medication are overwhelmingly lacking specific functional tests, we aimed to implement testing in routine stroke care.MethodsWe used fluorescence-activated cell sorting (FACS) with antibodies against CD61 for thrombocyte identification and CD62p or platelet activation complex-1 (PAC-1) to determine platelet activation. Aggregometry and automated platelet functioning analyzer (PFA-200) were employed to test thrombocyte reactivity. FACS and aggregometry samples were stimulated in vitro with arachidonic acid (AA) and adenosine diphosphate (ADP) to measure increase in CD62p-/PAC-1-expression or aggregation, respectively.ResultsBetween February and July 2023, 20 blood samples (n = 11 ischemic strokes; n = 7 hemorrhagic strokes; n = 2 controls) were acquired and analyzed within 24 h of symptom onset. N = 11 patients had taken ASA, n = 8 patients no APT and n = 1 ASA+clopidogrel. ASA intake compared to no APT was associated with lower CD62p expression after stimulation with AA on FACS analysis (median 15.8% [interquartile range {IQR} 12.6–37.2%] vs. 40.1% [IQR 20.3–56.3%]; p = 0.020), lower platelet aggregation (9.0% [IQR 7.0–12.0%] vs. 88.5% [IQR 11.8–92.0%]; p = 0.015) and longer time to plug formation with PFA-200 (248.0 s [IQR 157.0–297] vs. 121.5 s [IQR 99.8–174.3]; p = 0.027). Significant correlations were noted between AA-induced CD62p expression and aggregometry analysis (n = 18; ρ = 0.714; p &lt; 0.001) as well as a negative correlation between CD62p increase and PFA clot formation time (n = 18; ρ = −0.613; p = 0.007). Sensitivity for ASA intake was highest for PFA (81.8% for values ≥155.5 s). The combination of ASA + clopidogrel also affected ADP-induced CD62p and PAC-1 expression.ConclusionIn the clinical setting it is feasible to use differentiated platelet analytics to determine alterations caused by antiplatelet therapy. Among the tests under investigation, PFA-200 showed the highest sensitivity for the intake of ASA in stroke patients. FACS analysis on the other hand might be able to provide a more nuanced approach to altered platelet reactivity.