bluuebunny/crossref_metadata_2025_split huggingface dataset:
Causal relationship between plasma lipidome and four types of pancreatitis: a bidirectional Mendelian randomization study
Authors: Ma Runzhou , Chen Chengming , Wang Ziyi , Guo Huaibin , Zhang Wanxing 
Published: September 2024

BackgroundPancreatitis is a serious and complex inflammatory disease that imposes a severe effect on quality of life. Links between plasma lipidome and pancreatitis have been reported, some of which have not yet been clearly elucidated.MethodsTherefore, our study aimed to investigate the causal relationships between plasma lipidome and four types of pancreatitis by conducting a bidirectional, two-sample Mendelian randomization (MR) analysis. We obtained genetic variants associated with 179 lipid species from a Genome-wide association analysis of plasma lipidome. The aggregated statistical data of acute pancreatitis (AP), alcohol-induced acute pancreatitis (AAP), chronic pancreatitis (CP), and alcohol-induced chronic pancreatitis (ACP) from the FinnGen consortium were exploited as the outcome. The inverse variance weighted (IVW) technique as the main method was used for MR analysis and sensitivity analyses were used to evaluate heterogeneity and pleiotropy.ResultsAfter FDR correction, SE (27:1/20:4) (OR = 0.938, 95%CI = 0.906-0.972, P = 4.38 × 10-4, PFDR = 0.039) was identified to be significantly associated with AP risk. Eight lipid species were identified to be significantly associated with CP risk: SE (27:1/20:4) (OR = 0.911, 95%CI = 0.869-0.954, P = 8.89 × 10-5, PFDR = 0.016), LPC (20:4) (OR = 0.892, 95%CI = 0.843-0.945, P = 9.74 × 10-5, PFDR = 0.009), PC (16:0_22:5) (OR = 0.880, 95%CI = 0.818-0.947, P = 6.29 × 10-4, PFDR = 0.028), PC (17:0_20:4) (OR = 0.893, 95%CI = 0.842-0.948, P = 1.76 × 10-4, PFDR = 0.010), PC (18:0_20:4) (OR = 0.920, 95%CI = 0.874-0.969, P = 1.70 × 10-3, PFDR = 0.038), PC (O-16:0/20:4) (OR = 0.871, 95%CI = 0.804-0.943, P = 6.95 × 10-4, PFDR = 0.025), PC (O-16:1/20:4) (OR = 0.890, 95%CI = 0.832-0.953, P = 7.85 × 10-4, PFDR = 0.023), and PE (O-18:1/20:4) (OR = 0.866, 95%CI = 0.791-0.947, P = 1.61 × 10-3, PFDR = 0.041). Furthermore, genetically predicted increased LPC (20:4) (OR = 0.862, 95%CI = 0.796-0.934, P = 3.00 × 10-4, PFDR = 0.027) and SM (34:2;O2) (OR = 0.753, 95%CI = 0.659-0.860, P = 2.97 × 10-5, PFDR = 0.005) levels were associated with decreased risk of ACP.ConclusionsOur findings provide evidence of causal associations between the specific types of lipidome and pancreatitis, offering new insights into future clinical research.
The role of glycemic traits in the mediation of the causal effect of hypothyroidism on coronary heart disease
Authors: Jin Zhiwei , Li Guorong , Xue Zekuan , Li Yijie , Yang Wangfang , Yu Yunfei , Hou Jixue 
Published: September 2024

BackgroundHypothyroidism and coronary heart disease are both common diseases in life and both are increasing in prevalence. Many studies have found a strong association between the two. However, they have not been able to prove a causal relationship. Furthermore, numerous studies have demonstrated that glycemic traits play a role in both. Consequently, the objective of this study was to ascertain the causal estimation of the association between hypothyroidism and coronary heart disease and to quantify the potential mediating role of glycemic traits in this relationship.MethodsWe used two-sample Mendelian randomisation (UVMR) to explore causality between hypothyroidism and coronary heart disease. Additionally, multivariate Mendelian randomisation (MVMR) was applied to quantify the potential mediation of glycemic traits in this relationship. A variety of Mendelian randomization methods were employed in this study, including the inverse variance weighting (IVW) method, weighted median method, and MR-Egger test. Heterogeneity and horizontal pleiotropy were evaluated through MR-Egger intercept test, Cochran’s Q test, and leave-one-out analysis to ensure the robustness of the study results.ResultsThe results of the MR analyses indicated that hypothyroidism was associated with an increased risk of coronary heart disease (IVW: OR=2.75, 95% CI: 1.53-4.94). In mediation analyses, the proportion of HbA1c-mediated effects of hypothyroidism on coronary heart disease was 7.3% (2.2%-12.5%).ConclusionThe results of our study indicate a causal relationship between hypothyroidism and coronary heart disease. Furthermore, HbA1c partially mediated the causal effect of hypothyroidism on coronary heart disease. Consequently, intervention in this factor may reduce the risk of coronary heart disease associated with hypothyroidism.
Development of a COVID-19 early risk assessment system based on multiple machine learning algorithms and routine blood tests: a real-world study
Authors: Qin Qiangqiang , Li Qingxuan , Zhu Guiyin , Yu Haiyang , Peng Mingyan , Wu Shuang , Xu Xue , Gu Wen , Guo Xuejun 
Published: September 2024

BackgroundsDuring the Coronavirus Disease 2019 (COVID-19) epidemic, the massive spread of the disease has placed an enormous burden on the world’s healthcare and economy. The early risk assessment system based on a variety of machine learning (ML) algorithms may be able to provide more accurate advice on the classification of COVID-19 patients, offering predictive, preventive, and personalized medicine (PPPM) solutions in the future.MethodsIn this retrospective study, we divided a portion of the data into training and validation cohorts in a 7:3 ratio and established a model based on a combination of two ML algorithms first. Then, we used another portion of the data as an independent testing cohort to determine the most accurate and stable model and compared it with other scoring systems. Finally, patients were categorized according to risk scores and then the correlation between their clinical data and risk scores was studied.ResultsThe elderly accounted for the majority of hospitalized patients with COVID-19. The C-index of the model constructed by combining the stepcox[both] and survivalSVM algorithms was 0.840 in the training cohort and 0.815 in the validation cohort, which was calculated to have the highest C-index in the testing cohort compared to the other 119 ML model combinations. Compared with current scoring systems, including the CURB-65 and several reported prognosis models previously, our model had the highest AUC value of 0.778, representing an even higher predictive performance. In addition, the model’s AUC values for specific time intervals, including days 7,14 and 28, demonstrate excellent predictive performance. Most importantly, we stratified patients according to the model’s risk score and demonstrated a difference in survival status between the high-risk, median-risk, and low-risk groups, which means a new and stable risk assessment system was built. Finally, we found that COVID-19 patients with a history of cerebral infarction had a significantly higher risk of death.ConclusionThis novel risk assessment system is highly accurate in predicting the prognosis of patients with COVID-19, especially elderly patients with COVID-19, and can be well applied within the PPPM framework. Our ML model facilitates stratified patient management, meanwhile promoting the optimal use of healthcare resources.
IGFBP7+ subpopulation and IGFBP7 risk score in astrocytoma: insights from scRNA-Seq and bulk RNA-Seq
Authors: Zhao Liang , Shao Wenwen , Xiahou Zhikai , Ren Li , Liu Chaobo , Song Yanbing , Xu Hao , Wang Zhihan , Xing Jin 
Published: September 2024

BackgroundGlioma is the predominant malignant brain tumor that lacks effective treatment options due to its shielding by the blood-brain barrier (BBB). Astrocytes play a role in the development of glioma, yet the diverse cellular composition of astrocytoma has not been thoroughly researched.MethodsWe examined the internal diversity of seven distinct astrocytoma subgroups through single-cell RNA sequencing (scRNA-seq), pinpointed crucial subgroups using CytoTRACE, monocle2 pseudotime analysis, and slingshot pseudotime analysis, employed various techniques to identify critical subgroups, and delved into cellular communication analysis. Then, we combined the clinical information of GBM patients and used bulk RNA sequencing (bulk RNA-seq) to analyze the prognostic impact of the relevant molecules on GBM patients, and we performed in vitro experiments for validation.ResultsThe analysis of the current study revealed that C0 IGFBP7+ Glioma cells were a noteworthy subpopulation of astrocytoma, influencing the differentiation and progression of astrocytoma. A predictive model was developed to categorize patients into high- and low-scoring groups based on the IGFBP7 Risk Score (IGRS), with survival analysis revealing a poorer prognosis for the high-IGRS group. Analysis of immune cell infiltration, identification of genes with differential expression, various enrichment analyses, assessment of copy number variations, and evaluation of drug susceptibility were conducted, all of which highlighted their significant influence on the prognosis of astrocytoma.ConclusionThis research enhances comprehension of the diverse cell composition of astrocytoma, delves into the various factors impacting the prognosis of astrocytoma, and offers fresh perspectives on treating glioma.
Unveiling signaling pathways inducing MHC class II expression in neutrophils
Authors: Forrer Pascal , Palianina Darya , Stühler Claudia , Kreuzaler Matthias , Roux Julien , Li Jiagui , Schmutz Christoph , Burckhardt David , Franzeck Fabian , Finke Daniela , Schmidt Alexander , Bumann Dirk , Khanna Nina 
Published: September 2024

IntroductionGram-negative bacillary bacteremia poses a significant threat, ranking among the most severe infectious diseases capable of triggering life-threatening sepsis. Despite the unambiguous involvement of neutrophils in this potentially fatal disease, there are limited data about the molecular signaling mechanisms, phenotype, and function of human neutrophils during the early phase of gram-negative bacillary bacteremia.MethodsBy using an unbiased proteomics and flow cytometry approach, we identified an antigen-presenting cell (APC)-like phenotype in human peripheral blood neutrophils (PMN) with MHC class II molecule expression in the early phase of bacteremia. Using an in-vitro model of GM-CSF-mediated induction of APC-like phenotype in PMN, we investigated downstream signaling pathways leading to MHC class II expression.ResultsGM-CSF stimulation of neutrophils leads to the activation of three major signaling pathways, the JAK-STAT, the mitogen-activated protein kinase (MAPK), and the phosphoinositide 3-kinase (PI3K)-Akt-mTOR pathways, while MHC class II induction is mediated by a MAPK-p38-MSK1-CREB1 signaling cascade and the MHC class II transactivator CIITA in a strictly JAK1/2 kinase-dependent manner.DiscussionThis study provides new insights into the signaling pathways that induce MHC class II expression in neutrophils, highlighting the potential for therapeutic targeting of JAK1/2 signaling in the treatment of gram-negative bacteremia and sepsis. Understanding these mechanisms may open up novel approaches for managing inflammatory responses during sepsis.
Frailty assessment and outcomes in primary care for patients with diabetes during Ramadan: implications for risk evaluation and care plans
Authors: Baynouna Alketbi Latifa Mohammad , Afandi Bachar , Nagelkerke Nico , Abdubaqi Hanan , Al Nuaimi Ruqaya Abdulla , Al Saedi Mariam Rashed , Al Blooshi Fatima Ibrahim , Al Blooshi Noura Salem , Al Aryani Aysha Mohammed , Al Marzooqi Nouf Mohammed , Al Khouri Amal Abdullah , Al Mansoori Shamsa Ahmed , Hassanein Mohammad 
Published: September 2024

BackgroundFrailty is a critical concern for older adults, impacting their susceptibility to adverse events and overall quality of life. This study aimed to determine the frailty status of patients 60 years or older in Abu Dhabi Ambulatory Healthcare Services (AHS) and assess its relation to the stress exerted by Ramadan fasting and the occurrence of any adverse outcomes.MethodsIn this prospective observational study, participants were included if the attending physicians used the IDF-DAR risk stratification assessment tool. A tele-interview was conducted to complete the FRAIL score within 6 weeks before Ramadan 1,444 (CE 2022). The outcome was assessed through another tele-interview and an electronic medical record review after Ramadan.ResultsAccording to the FRAIL assessment tool, among the 204 patients aged 60 years or older included in the study, 109 (53.4%) were classified as either frail or pre-frail. In total, 20 (9.8%) patients were frail, that is, 1 out of 10, and 89 (43.6%) were pre-frail. The remaining 95 (46.6%) patients were robust. Using logistic regression to assess the occurrence of adverse outcomes after Ramadan fasting, a higher frailty score was identified as the third independent risk factor [B = 0.4, OR = 1.5 (1–2.02–1.86), and p = 0.039] for experiencing an adverse event. The identified factors associated with frailty were age, increased albumin-to-creatinine ratio (ACR), chronic kidney diseases (CKDs), and ischemic heart diseases (beta = 0.27, p = 0.003; beta = 0.24, p = 0.004; beta = 0.2, p = 0.039; and beta = 0.18, p = 0.041, respectively). One-third of the frail patients had an event, while the incidence in pre-frail patients was 11.2%, and among the robust patients, the incidence was 6.3%. Physicians’ global assessment of frailty did not align well with the structured FRAIL scoring. Only five (25%) out of the 20 patients identified as frail by the FRAIL assessment tool were also judged as frail or having cognitive function impairment by the physicians’ global assessment tool.ConclusionFrailty is prevalent among elderly patients with diabetes. Disparity exists between subjective and objective frailty assessments, emphasizing the need for standardized evaluation methods. Using the FRAIL tool is recommended for patients aged 60 or older with diabetes in Abu Dhabi.
Itaconate induces tolerance of Staphylococcus aureus to aminoglycoside antibiotics
Authors: Zhao Runping , Xu Lei , Chen Jieyun , Yang Yanxian , Guo Xilong , Dai Min , Tian Guo-Bao , Qin Li-Na 
Published: September 2024

IntroductionStaphylococcus aureus is one of the chief pathogens that cause chronic and recurrent infections. Failure of the antibiotics to curb the infections contributes to relapse and is an important reason for the high mortality rate. Treatment failure may also be due to antibiotic tolerance. Accumulating evidence suggests that t the host immune environment plays an important role in inducing antibiotic tolerance of S. aureus, but research in this area has been limited.MethodsIn this study,the minimum inhibitory concentration (MIC) of the antibiotics against S. aureus was determined using the standard broth microdilution method.The study evaluated whether itaconate induces antibiotic tolerance in S. aureus through an antibiotic bactericidal activity assay.The effect of itaconate on the growth of S. aureus was evaluated by monitoring the growth of S. aureus in medium supplemented with itaconate. Additionally, RNA sequencing and metabolomics analyses were used to determine transcriptional and metabolic changes in S. aureus when exposed to itaconate.Results and discussionAccording to the study,we found that the immune metabolite itaconate can induce tolerance in both methicillin-resistant and -susceptible S. aureus to aminoglycosides. When S. aureus was exposed to itaconate, its growth slowed down and transcriptomic and metabolomic alterations associated with decreased energy metabolism, including the tricarboxylate cycle, glycolysis, pyruvate metabolism, and arginine biosynthesis, were observed. These changes are associated with aminoglycoside tolerance. This study highlights the role of immune signaling metabolites in bacterial antibiotic tolerance and suggests new strategies to improve antibiotic treatment by modulating the host immune response and stimulating the metabolism of bacteria.
Incidence, risk factors and outcomes of traumatic head injury among trauma patients visited at the Yanet Trauma and Surgery Specialized Centre, Sidama region, Hawassa, Ethiopia: cohort study
Authors: Abebe Tadelech , Alemu Tsegaye , Sorato Mende Mensa 
Published: September 2024

IntroductionTraumatic brain injuries are a major public health concern that contributes to youth morbidity and mortality in developing nations, including Ethiopia. Despite of this, little is known about head injury in the study area. The goal of the study was to identify the incidence, risk factors and outcomes for traumatic head injury among trauma patients who visited at the Yanet Trauma and Surgery Specialized Centre.MethodsThis was a 5 year an institutional-based retrospective cohort study conducted among 1,029 patients who experienced trauma and admitted at the Yanet Trauma and Surgical Specialized Centre. The research was carried out between September 01/2023 to October 15/2023. The study units were selected by using simple random sampling techniques through computer-generated random numbers. The data were collected via a checklist designed on the Kobo toolbox with a smart smartphone. The collected data were exported to a statistical package for Social Science version 27. Then, descriptive statistical analysis was conducted to determine the mean, standard deviation, and median. Bivariate and multivariate logistic regression was subsequently conducted to determine the associations between head injury and the independent variables.ResultA total of 1,029 injured patients were followed for 2,302 person-days. Over all, incidence density rate of 14.03/100 person-days (323, 31.4%) [95% CI: 29.5–34%]. The third year of follow-up showed the greatest incidence compared to other years. The most common type of head injury observed during following up were brain contusion (38.1%), followed by epidural hematoma (33.1%), skull fracture (15.8%), and intracerebral hematoma (13.0%). In multivariate logistic model, rural residence [AOR = 1.6; 95% CI: 1.18–2.16], mechanism of injury namely road traffic accident [AOR = 5.5; 95% CI: 2.27–13.34], assault [AOR = 3.4; 95% CI: 1.35–8.37] and comorbidity of chronic disease [AOR = 2.2; 95% CI: 1.13–4.18] were the risk factors significantly associated with head injury.DiscussionsThe incidence density rate of 14.03/100 person-days. As the result, more has to be done by health professionals, traffic police officers and local government raise awareness and enforce the implementation of driving rules and regulations.
Effects of repetitive transcranial magnetic stimulation at different targets on brain function in stroke patients: a randomized controlled trial
Authors: Zhao Li , Chen Li , Wang Chunyan , Li Sha , Wan Chunxiao 
Published: September 2024

IntroductionRepetitive transcranial magnetic stimulation (rTMS) can improve post stroke motor function. However, there is little research on targets. The purpose of this study is to investigate the effects of rTMS therapy with different targets on post stroke motor function and neural plasticity.MethodsFifty-four subjects were randomly divided into M1 (Primary motor area) group, SMA (supplementary motor area) group and Sham group, and were given 10 Hz on the affected M1 area, SMA area and sham stimulation rTMS. The primary outcomes included Fugl-Meyer Assessment Upper Extremity Scale (FMA-UE), Fugl-Meyer Assessment Lower Extremity Scale (FMA-LE) and Berg balance scale (BBS). Secondary outcomes: amplitude of low frequency fluctuation (ALFF), regional homogeneity (ReHo) and functional connectivity (FC) were analyzed by functional magnetic resonance imaging (fMRI) to evaluate brain functional activation and functional connectivity changes.ResultsThe 2-way repeated-measures ANOVA revealed a significant group × time interaction (F = 23.494, p &lt; 0.001; F = 10.801, p &lt; 0.001; F = 17.812, p &lt; 0.001) in the FMA-UE, FMA-LE and BBS scores. Post hoc analysis indicated that 4 weeks of SMA rTMS resulted in an increase in FMA-UE, FMA-LE and BBS scores compared with Sham group (p = 0.006; p = 0.033; p = 0.012), SMA group was significantly increased in BBS compared with M1 group (p = 0.034). Moreover, there were significant effects of time in all 3 groups in the FMA-UE, FMA-LE and BBS scores (p &lt; 0.001). In addition, the increase of ALFF in the supramarginal gyrus on the affected side was correlated with better FMA-UE recovery, the increase of ALFF in the middle temporal gyrus and the middle frontal gyrus on the affected side was positively correlated with the improvement of BBS, and the ALFF in the cerebellum on the healthy side was negatively correlated with the improvement of BBS. There was a positive correlation between FC (SMA – ipsilateral cerebellum) changes and BBS changes in SMA group.DiscussionIn conclusion, SMA-rTMS intervention has a better recovery effect on motor dysfunction after stroke than Sham-rTMS. SMA-rTMS led to similar improvement on motor function but significantly greater improvement on balance compared to M1-rTMS, and this may pave a new way for stroke rehabilitation.Clinical trial registrationRegistration number: ChiCTR2200060955, https://www.chictr.org.cn/.
Investigating the pathophysiology and evolution of internal carotid dissection: a fluid–structure interaction simulation study
Authors: Bonura Adriano , Musotto Giulio , Iaccarino Gianmarco , Rossi Sergio Soeren , Calandrelli Rosalinda , Capone Fioravante , Di Lazzaro Vincenzo , Pilato Fabio 
Published: September 2024

BackgroundArterial dissection, a condition marked by the tearing of the carotid artery’s inner layers, can result in varied clinical outcomes, including progression, stability, or spontaneous regression. Understanding these outcomes’ underlying mechanisms is crucial for enhancing patient care, particularly with the increasing use of computer simulations in medical diagnostics and treatment planning. The aim of this study is to utilize computational analysis of blood flow and vascular wall to: (1) understand the pathophysiology of stroke-like episodes in patients with carotid artery dissection; and (2) assess the effectiveness of this method in predicting the evolution of carotid dissection.MethodsUtilizing contrast-enhanced magnetic resonance angiography (MRA), we segmented images of the patient’s right internal carotid artery. These images were transformed into 3D solids for simulation in Ansys multifisic software, employing a two-way fluid structure interaction (FSI) analysis. Simulations were conducted across two wall conditions (atherosclerotic and normal) and three pressure states (hypotension, normotension, hypertension).ResultsThe simulations indicated a significant pressure discrepancy between the true and false lumens of the artery. This suggests that flap motion and functional occlusion under hypertensive conditions could be the cause of the clinical episodes. Thrombotic risk and potential for dissection extension were not found to be critical concerns. However, a non-negligible risk of vessel dilation was assessed, aligning with the patient’s clinical follow-up data.ConclusionThis study highlights specific hemodynamic parameters that could elucidate carotid artery dissection’s mechanisms, offering a potential predictive tool for assessing dissection progression and informing personalized patient care strategies.