bluuebunny/crossref_metadata_2025_split huggingface dataset:
Causal effects of gut microbiome on hypertension: a Mendelian randomization study
Authors: He Gang , Cao Yu , Wang Houzhao , Lv Xiaoying 
Published: November 2023

BackgroundPrevious observational studies have shown that there is an important relationship between gut microbiota and hypertension, we performed a two-sample Mendelian randomization analysis to examine whether the gut microbiota is causally related to hypertension in order to find a basis for potential diagnostic or intervention approaches for hypertension.MethodsWe obtained significant single nucleotide polymorphisms related to gut microbiota and hypertension from publicly available genome-wide association studies for a two-sample Mendelian randomization study. A total of 18,340 individual genome-wide genotype data were included from 24 population-based cohorts. The inverse-variance weighted meta-analysis is the main analytical method for evaluating causal relationships, and the Mendelian randomization research results have been validated through a series of sensitivity analyses.ResultsThe inverse-variance weighted analysis results indicated that phylum Verrucomicrobia (OR:0.831, 95%CI: 0.710–0.972; p = 0.021), family BacteroidalesS24.7group (OR:0.672, 95%CI: 0.496–0.911; p = 0.01), family Bifidobacteriaceae (OR:0.709, 95%CI:0.569–0.884, p = 0.002), genus Adlercreutzia (OR: 0.991, 95%CI: 0.982–0.999, p = 0.035), genus Phascolarctacterium (OR:0.819, 95%CI:0.685–0.981; p = 0.03), genus LachnospiraceaeNK4A136group (OR:0.990, 95%CI:0.981–0.999; p = 0.025), and genus Ruminococcus2 (OR:0.988, 95%CI: 0.979–0.997; p = 0.008) had protective causal effects on hypertension. The Family Alcaliginaceae (OR:1.011, 95%CI:1.000–1.021, p = 0.04), Genus Anaerostipes (OR:1.375, 95%CI:1.096–1.653; p = 0.025), Genus Collinsella (OR:1.899, 95%CI:1.361–2.348; p = 0.02), and Genus Lachnospiraceae_UCG_010 (OR:1.536, 95%CI:1.072–2.202; p = 0.019) were associated with a higher risk of HTN. The reverse Mendelian randomization analysis results showed no reverse causal relationship between HTN and these bacterial taxa.ConclusionOur Mendelian randomization analysis results indicate a potential causal relationship between these bacterial taxa and hypertension, providing a new perspective for the treatment and prevention of hypertension.
Role of the microtubules in the electrical activity of the primary cilium of renal epithelial cells
Authors: Scarinci Noelia , Gutierrez Brenda C. , Albarracín Virginia H. , Cantero María del Rocío , Cantiello Horacio F. 
Published: November 2023

The primary cilium is a non-motile sensory organelle that transduces environmental cues into cellular responses. It comprises an axoneme, a core of nine doublet microtubules (MTs) coated by a specialized membrane populated by receptors, and a high density of ion channels. Dysfunctional primary cilia generate the pathogenesis of several diseases known as ciliopathies. However, the electrical role of MTs in ciliary signaling remains largely unknown. Herein, we determined by the patch clamp technique the electrical activity of cytoplasmic and axonemal MTs from wild-type LLC-PK1 renal epithelial cells. We observed electrical oscillations with fundamental frequencies at ∼39 Hz and ∼93 Hz in sheets of cytoplasmic MTs. We also studied in situ and isolated, intact and Triton X-permeabilized primary cilia, observing electrical oscillations with peak frequencies at either 29–49 Hz (non-permeabilized) or ∼40–49 Hz (permeabilized) and ∼93 Hz (both). We applied Empirical Mode Decomposition (EMD), Continuous Wavelet Transform (CWT), and Cross-Correlation Analysis (CCA) to assess the differences and the coherence in the Time-Frequency domains of electrical oscillations between cytoplasmic and axonemal MTs. The data indicate that axonemal and cytoplasmic MTs show different patterns of electrical oscillations preserving coherence at specific frequency peaks that may serve as electromagnetic communication between compartments. Further, the electrical behavior of axonemal MTs was modified by siRNA deletion of polycystin-2 (PC2), which lengthens primary cilia, thus linking ciliary channels to the morphological and electrical behavior of cilia in ciliopathies. The encompassed evidence indicates that the primary cilium behaves as an electrical antenna, with an excitable MT structure that produces electrical oscillations whose synchronization and propagation constitute a novel cell signaling mechanism.
Period2 is associated with immune cell infiltration and is a potential diagnostic and prognostic marker for hepatocellular carcinoma
Authors: Chen Xiaolin , Zhao Qiaosu , Wang Haibiao , Qiu Kaijie , Deng Xi , Xu Feng 
Published: November 2023

Background: Hepatocellular carcinoma (HCC) health challenge worldwide. Many studies showed that circadian rhythms play a critical role in tumor development. This study aimed to investigate the role of the circadian gene period2 (PER2) in HCC development and explore the possible mechanisms involved.Methods: From fresh HCC tissues and paired paracancerous tissues, we measured PER2 mRNA and protein expression levels and calculated the correlations between PER2 expression and clinicopathological parameters in patients with HCC. We used transcriptome data from The Cancer Genome Atlas to mine the PER2 gene, including single gene difference analysis, single gene co-expression analysis, gene set enrichment analysis, immune infiltration analysis, and methylation analysis to explore its role and mechanism in HCC occurrence and development.Results: PER2 expression levels were significantly lower in HCC tissues than in the paired paracancerous tissues. PER2 expression in HCC significantly correlated with neural invasion, Child-Pugh classification, and China liver cancer staging stage in HCC patients. The differentially expressed genes associated with PER2 were significantly enriched in mitochondrial oxidative phosphorylation, transcriptional translation, amino acid metabolism, and other related pathways. PER2 expression levels significantly correlated with immune cell infiltration and immune checkpoint genes and positively correlated with TP53 expression in HCC tissues. The DNA methylation status in eight CpG islands of the PER2 gene was associated with HCC outcomes.Conclusion: PER2 is a potential diagnostic and prognostic biomarker and a promising therapeutic target in HCC.
Potent VEGFR-2 inhibitors for resistant breast cancer: a comprehensive 3D-QSAR, ADMET, molecular docking and MMPBSA calculation on triazolopyrazine derivatives
Authors: Baammi Soukayna , El Allali Achraf , Daoud Rachid 
Published: November 2023

More people are being diagnosed with resistant breast cancer, increasing the urgency of developing new effective treatments. Several lines of evidence suggest that blocking the kinase activity of VEGFR-2 reduces angiogenesis and slows tumor growth. In this study, we developed novel VEGFR-2 inhibitors based on the triazolopyrazine template by using comparative molecular field analysis (CoMFA) and molecular similarity indices (CoMSIA) models for 3D-QSAR analysis of 23 triazolopyrazine-based compounds against breast cancer cell lines (MCF -7). Both CoMFA (Q2 = 0.575; R2 = 0.936, Rpred2 = 0.956) and CoMSIA/SE (Q2 = 0.575; R2 = 0.936, Rpred2 = 0.847) results demonstrate the robustness and stability of the constructed model. Six novel compounds with potent inhibitory activity were carefully designed, and screening of ADMET properties revealed their good oral bioavailability and ability to diffuse through various biological barriers. When compared with the most active molecule in the data set and with Foretinib (breast cancer drug), molecular docking revealed that the six designed compounds had strengthened affinity (−8.9 to −10 kcal/mol) to VEGFR-2. Molecular Dynamics Simulations and MMPBSA calculations were applied to the selected compound T01 with the highest predicted inhibitory activity, confirming its stability in the active pocket of VEGFR-2 over 100 ns. The present results provided the basis for the chemical synthesis of new compounds with improved inhibitory properties against the breast cancer cell line (MCF -7).
Association between oral microbiome and seven types of cancers in East Asian population: a two-sample Mendelian randomization analysis
Authors: Feng Kexin , Ren Fei , Wang Xiang 
Published: November 2023

Background: The oral microbiome has been intricately linked to various pathological conditions, notably cancer, though clear causal links remain elusive. This study aimed to investigate the potential causal relationships between the oral microbiome and seven major cancers: breast, lung, pancreatic, colorectal, gastric, ovarian, and prostate cancers, leveraging Mendelian randomization (MR).Methods: A two-sample MR analysis was conducted using genome-wide association study (GWAS) data specific to oral microbiota in individuals of East Asian descent. Single nucleotide polymorphisms (SNPs) independent of confounders served as instrumental variables (IVs) to deduce causality. MR methodologies such as the inverse variance weighted (IVW) method, weighted median (WM) method, and Mendelian randomization-Egger (MR-Egger) method were employed. The study utilized datasets encapsulating a multitude of cancer cases and controls, focusing on Asian populations.Results: Our analysis revealed intricate associations between specific bacterial genera of the oral microbiome and diverse cancers. Notably, Fusobacterium showed mixed associations with various cancers, while genera like Prevotella and Streptococcus exhibited nuanced roles across malignancies. The genus Aggregatibacter demonstrated a multifaceted influence, positively correlating with some cancers while inhibiting others.Conclusion: Our findings underscore the profound implications of the oral microbiome in systemic malignancies, suggesting potential modulatory roles in cancer etiology. These insights, though preliminary, accentuate the need for deeper exploration and could pave the way for novel therapeutic strategies.
Examining the efficacy of a cardio-dance intervention on brain health and the moderating role of ABCA7 in older African Americans: a protocol for a randomized controlled trial
Authors: Gluck Mark A. , Gills Joshua L. , Fausto Bernadette A. , Malin Steven K. , Duberstein Paul R. , Erickson Kirk I. , Hu Liangyuan 
Published: November 2023

IntroductionAfrican Americans are two to three times more likely to be diagnosed with Alzheimer’s disease (AD) compared to White Americans. Exercise is a lifestyle behavior associated with neuroprotection and decreased AD risk, although most African Americans, especially older adults, perform less than the recommended 150 min/week of moderate-to-vigorous intensity exercise. This article describes the protocol for a Phase III randomized controlled trial that will examine the effects of cardio-dance aerobic exercise on novel AD cognitive and neural markers of hippocampal-dependent function (Aims #1 and #2) and whether exercise-induced neuroprotective benefits may be modulated by an AD genetic risk factor, ABCA7 rs3764650 (Aim #3). We will also explore the effects of exercise on blood-based biomarkers for AD.Methods and analysisThis 6-month trial will include 280 African Americans (≥ 60 years), who will be randomly assigned to 3 days/week of either: (1) a moderate-to-vigorous cardio-dance fitness condition or (2) a low-intensity strength, flexibility, and balance condition for 60 min/session. Participants will complete health and behavioral surveys, neuropsychological testing, saliva and venipuncture, aerobic fitness, anthropometrics and resting-state structural and functional neuroimaging at study entry and 6 months.DiscussionResults from this investigation will inform future exercise trials and the development of prescribed interventions that aim to reduce the risk of AD in African Americans.
Case report: Mononeuropathy multiplex of extranodal natural killer/T-cell lymphoma misdiagnosed as systemic vasculitis
Authors: Shi Jiayu , Niu Jingwen , Wu Di , Zhang Lei , Huang Yangyu , Zhang Hui , Guan Hongzhi , Liu Mingsheng , Guan Yuzhou 
Published: November 2023

BackgroundExtranodal NK/T-cell lymphoma (ENKTL) is an aggressive non-Hodgkin lymphoma that typically develops in the upper aerodigestive tract.Case presentationWe encountered an ENKTL patient who presented with purpura-like rashes and foot drops as initial symptoms and later developed other peripheral nerve involvement. The nerve conduction study of both the motor nerve and the sensory nerve showed axonal damage resembling mononeuropathy multiplex. Although the initial response to steroids was encouraging, the patient's symptoms reappeared and aggravated. A biopsy of the abdominal subcutaneous fat tissue with additional immunohistochemistry revealed neoplastic NK/T lymphocytes.ConclusionWe reported the first case presented as mononeuropathy multiplex as the initial clinical manifestation in ENKTL patients. Lymphoma should be considered in the diagnosis of atypical mononeuropathy in multiplex patients.
Bibliometric and visual analysis of spinal cord injury-associated macrophages from 2002 to 2023
Authors: Zhao Yan , Xia Qiuqiu , Zong Hui , Wang Yanyang , Dong Huaize , Zhu Lu , Xia Jiyue , Mao Qiming , Weng Zijing , Liao Wenbo , Xin Zhijun 
Published: November 2023

BackgroundSpinal cord injury (SCI) triggers motor, sensory, and autonomic impairments that adversely damage patients' quality of life. Its pathophysiological processes include inflammation, oxidative stress, and apoptosis, although existing treatment options have little success. Macrophages have a vital function in controlling inflammation in SCI, with their M1-type and M2-type macrophages dominating early inflammatory effects and late brain tissue repair and regeneration, respectively. However, there is a dearth of rigorous bibliometric study in this sector to explore its dynamics and trends. This study intends to examine the current status and trends of macrophage usage in SCI using bibliometric methodologies, which may drive novel therapeutic options.MethodsIn this study, the Web of Science Core Collection (WOSCC) was utilized to collect publications and reviews on macrophages in SCI from 2002 to 2023. Bibliometrics and visualization analyses were performed by VOSviewer, CiteSpace, the R package “bibliometrix”, and online analytic platforms. These analyses covered a variety of aspects, including countries and institutions, authors and co-cited authors, journals and co-cited journals, subject categories, co-cited references, and keyword co-occurrences, in order to provide insights into the research trends and hotspots in this field.Results1,775 papers were included in the study, comprising 1,528 articles and 247 reviews. Our research analysis demonstrates that the number of relevant studies in this sector is expanding, specifically the number of publications in the United States and China has risen dramatically. However, there are fewer collaborations between institutions in different nations, and international cooperation needs to be reinforced. Among them, Popovich PG became the leader in the field, and significant journals include Experimental Neurology, Journal of Neurotrauma, and Journal of Neuroscience. Research hotspots involve macrophage polarization, microglia, astrocytes, signaling, cytokines, inflammation, and neuroprotection.ConclusionsThis analysis gives, for the first time, a comprehensive overview of bibliometric studies on macrophages in SCI over the past 20 years. This study not only gives an extensive picture of the knowledge structure but also indicates trends in the subject. The systematic summarization gives a complete and intuitive understanding of the link between spinal cord damage and macrophages and provides a great reference for future related studies.
Study protocol for FIBROKIT: a new tool for fibromyalgia diagnosis and patient follow-up
Authors: del Amo Laura Lucena , Durán-González Elena , Ramírez-Tejero Jorge A. , Martínez-Lara Antonio , Cotán David 
Published: November 2023

Fibromyalgia (FM) is a complex disease that is characterized by chronic musculoskeletal pain and has great economic impact. FM prevalence is about 2% to 4% worldwide, affecting mainly middle-aged women, and its complex pathophysiology complicates diagnosis, treatment and the findings of solid biomarkers. Previous studies have suggested an association between the disease and oxidative stress, mitochondrial metabolism, intestinal microbiota and inflammation, providing sufficient data to support the multifactorial origin of FM. Hence, the objective of this randomized, prospective, low-interventional, double-blinded and placebo-controlled clinical trial is the development of a specific panel of FM biomarkers and the evaluation of their response to a six-month nutritional intervention based on the Mediterranean diet supplemented with extra virgin olive oil (EVOO). For this purpose, the experimental design implies the recruitment of a large cohort of female Spanish patients. Middle-aged women who meet the diagnostic criteria for FM according to the American College of Rheumatology (ACR) will be eligible, along with age-matched healthy women. Both groups will be randomly divided into placebo (olive oil, OO) and treatment groups (extra virgin olive oil, EVOO), and will provide samples at the beginning (T0), after 3 months of nutritional intervention (T1), at the end of the nutritional intervention in 6 months (T2), and 6 months after the end of nutritional intervention (TF), being enrolled for 1 year. Data will be collected through health questionnaires, and whole blood and stool samples will be taken and analyzed. Blood will be used for western-blotting and proteomic analysis of mitochondrial homeostasis and plasma proteome, while stool will undergo metagenomic analysis, respectively. This study represents the first low-interventional investigation with more than 200 participants focused on exploring the association of oxidative stress, mitochondrial metabolism, intestinal microbiota and related pathways with a nutritional intervention in the context of FM. As a result, the outcomes of this study will significantly contribute to the development of a comprehensive and robust panel of diagnostic biomarkers, and will shed some light on their modulation with non-pharmacological therapies such as nutrition.Clinical trial registration: https://clinicaltrials.gov/study/NCT05921409, identifier: NCT05921409.
A comprehensive two-sample Mendelian randomization analysis of trigeminal neuralgia and modifiable risk factors
Authors: Wei Xingrong , Zhou Hao , Zhang Shuguang , Hu Xueqian , Wei Zhenqin , Li Yang 
Published: November 2023

ObjectiveTo conduct a comprehensive search and causality study of potential modifiable risk factors for trigeminal neuralgia. To provide new ideas for subsequent treatment and management of patients with trigeminal neuralgia.MethodsData were obtained from large GWAS databases and then analyzed by Mendelian randomization analysis. The causal relationship between 36 potentially modifiable risk factors and trigeminal neuralgia was explored based on the results of the inverse variance weighting method(IVW). p &lt; 0.05 was considered statistically significant.ResultsYears of schooling [OR (95%CI), 0.59(0.42–0.84), p = 0.003] to be a significant protective factor. Anxiety disorders [OR (95%CI), 1.62(1.05–2.48), p = 0.028], Depression [OR (95%CI), 1.53(1.03–2.28), p = 0.035] and Autoimmune [OR (95%CI), 1.16(1.01–1.32), p = 0.033] were significant risk factors. Sleep duration [OR (95%CI), 0.43(0.18–1.01), p = 0.051] was a close protective factor. Body mass index [OR (95%CI), 1.24(0.98–1.57), p = 0.077] was a close risk factor.ConclusionMendelian randomization analysis shows Years of schooling and Sleep duration as protective factors. Anxiety disorders, Depression, Autoimmune, and Body mass index are risk factors. This will help in the research of diagnosis, treatment, and mechanism of trigeminal neuralgia. And reduce the prevalence of trigeminal neuralgia through positive psychological and lifestyle interventions.
Treating seronegative neuromyelitis optica spectrum disorder with inebilizumab: a case report
Authors: Lehrieder Dominik , Zapantis Nikolaos , Pham Mirko , Schuhmann Michael Klaus , Haarmann Axel 
Published: November 2023

BackgroundNeuromyelitis optica spectrum disorder (NMOSD) is a devastating inflammatory disease of the central nervous system that is often severely disabling from the outset. The lack of pathognomonic aquaporin 4 (AQP4) antibodies in seronegative NMOSD not only hinders early diagnosis, but also limits therapeutic options, in contrast to AQP4 antibody-positive NMOSD, where the therapeutic landscape has recently evolved massively.Case presentationWe report a 56-year-old woman with bilateral optic neuritis and longitudinally extensive myelitis as the index events of a seronegative NMOSD, who was successfully treated with inebilizumab.ConclusionTreatment with inebilizumab may be considered in aggressive seronegative NMOSD. Whether broader CD19-directed B cell depletion is more effective than treatment with rituximab remains elusive.
Performance of plasma von Willebrand factor in acute traumatic brain injury: relations to severity, CT findings, and outcomes
Authors: Zeng Rong , Li Shaoping , Yu Jiangtao , Ma Haoli , Zhao Yan 
Published: November 2023

Backgroundvon Willebrand factor (VWF) has been widely recognized as a biomarker for endothelial cell activation in trauma and inflammation. Traumatic brain injury (TBI) is characterized by cerebral vascular injury and subsequent inflammation. The objective of this study was to investigate the correlation between VWF levels and clinical severity, as well as imaging abnormalities, in TBI patients. Additionally, the predictive value of VWF for patient outcomes was assessed.MethodsWe conducted a prospective study to recruit acute TBI patients who were admitted to the emergency department within 24 h. Healthy individuals from the medical examination center were recruited as the control group. This study aimed to compare the accuracy of VWF in discriminating TBI severity and imaging abnormalities with the Glasgow Coma Scale (GCS) and Rotterdam computed tomography (CT) scores. We also analyzed the predictive value of these outcomes using the Glasgow Outcome Scale (GOS) and 6-month mortality.ResultsThe plasma concentration of VWF in TBI patients (84.7 ± 29.7 ng/ml) was significantly higher than in healthy individuals (40 ± 8.8 ng/ml). There was a negative correlation between VWF levels and GCS scores, as well as a positive correlation between VWF levels and Rotterdam CT scores. The area under the curve (AUC) for VWF in discriminating mild TBI was 0.76 (95% CI: 0.64, 0.88), and for predicting negative CT findings, it was 0.82 (95% CI: 0.72, 0.92). Meanwhile, the AUC of VWF in predicting mortality within 6 months was 0.70 (95% CI: 0.56, 0.84), and for a GOS score lower 4, it was 0.78 (95% CI: 0.67, 0.88). Combining VWF with either the GCS or Rotterdam CT score improved the prediction ability compared to using VWF alone.ConclusionVWF levels were significantly elevated in patients with TBI compared with healthy individuals. Furthermore, VWF levels demonstrated a negative correlation with GCS scores and a positive correlation with Rotterdam CT scores. In terms of predicting mortality, VWF alone was not sufficient, but its predictive power was enhanced when combined with either the Rotterdam CT score or GCS. These findings suggest that VWF may serve as a potential biomarker for assessing the severity and prognosis of TBI patients.