bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel pathogenic variant in LMNA gene identified in a six-generation family causing atrial cardiomyopathy and associated right atrial conduction arrhythmias
Authors: Ning Shifeng , Han Min , Qiu Rujie , Hong Xiaoming , Xia Zhao , Liu Li , Liu Chengwei 
Published: July 2023

ObjectiveTo characterize the cardiac phenotype associated with the novel pathogenic variant (c.1526del) of LMNA gene, which we identified in a large, six-generation family.Methods and ResultsA family tree was constructed. The clinical data of living and deceased family members were collected. DNA samples from 7 family members were analyzed for LMNA mutations using whole-exome high-throughput sequencing technology. The clinical presentation of pathogenic variant carriers was evaluated. In this six-generation family (n = 67), one member experienced sudden death at the age of 40-years-old. Three pathogenic variant carriers were identified to possess a novel heterozygous deletion mutation in LMNA gene (HGVS: NM_170707.4, c.1526del) located at exon 9 of LMNA chr1:156137145, which creates a premature translational stop signal (p.Pro509Leufs*39) in the LMNA gene and results in an mutant lamin A protein product. The main symptoms of the pathogenic variant carriers were palpitation, fatigue, and syncope, which typically occurred around 20-years-old. AV-conduction block and non-sustained ventricular tachycardia were the first signs of disease and would rapidly progress to atrial standstill around 30-years-old. Significant right atrial enlargement and bicuspid aortic valve malformation was also commonly seen in patients who carried this pathogenic variant.ConclusionThe pathogenic variant of c.1526del p.P509Lfs*39 was a frameshift deletion located at exon 9 of LMNA chr1:156137145 and causes severe right atrial enlargement, sick sinus syndrome, atrial standstill, ventricular tachycardia, and bicuspid aortic valve malformation. Our findings expand the phenotypic spectrum of novel LMNA gene mutations.
Geriatric nutrition risk index in the prediction of all-cause and cardiovascular mortality in elderly hypertensive population: NHANES 1999–2016
Authors: Huo Xuan , Wu Meiyin , Gao Dongmei , Zhou YueShengzi , Han Xu , Lai Weilin , Wang Mengqi , Hang Yilun 
Published: July 2023

BackgroundHypertension is a major risk factor for the global burden of disease, and nutrition is associated with an increased risk of mortality from multiple diseases. Few studies have explored the association of nutritional risk with all-cause mortality and cardiovascular mortality in hypertension, and our study aims to fill this knowledge gap.MethodWe included data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2016 on a total of 10,037 elderly patients with hypertension. The nutritional status was evaluated using the Geriatric Nutrition Risk Index (GNRI). Kaplan-Meier survival analysis was performed to analyze the survival rates of different nutritional risk groups. COX proportional risk regression models were used to analyze the predictive effect of GNRI on all-cause mortality and cardiovascular mortality in hypertensive patients. Restricted cubic splines (RCS) were used to explore the nonlinear relationship between GNRI and mortality.ResultThe mean age of the hypertensive patients was 70.7 years. A total of 4255 (42.3%) all-cause mortality and 1207 (17.2%) cardiovascular mortality occurred during a median follow-up period of 106 months. Kaplan-Meier showed a more significant reduction in survival for the moderate to severe malnutrition risk of GNRI. The adjusted COX proportional hazards model showed that the hazard ratios for all-cause mortality and cardiovascular mortality in the moderate to severe malnutrition risk group for GNRI were 2.112 (95% CI, 1.377,3.240) and 2.604 (95% CI, 1.603,4.229), respectively. The RCS showed that increased GNRI was associated with a reduced risk of all-cause mortality and cardiovascular mortality risk reduction.ConclusionMalnutrition exposure assessed by GNRI effectively predicts the risk of all-cause mortality and cardiovascular mortality in the elderly with hypertension.
A scoping review of seismic risk communication in Europe
Authors: Musacchio Gemma , Saraò Angela , Falsaperla Susanna , Scolobig Anna 
Published: July 2023

Although earthquakes are a threat in many countries and considerable resources have been invested in safety regulations, communities at risk often lack awareness and preparedness. Risk communication is a key tool for building resilient communities, raising awareness, and increasing preparedness. Over the past 2 decades, seismic risk communication has evolved significantly. This has led to a reorientation from a predominantly “one-way”, top-down communication model to the promotion of new models in which people, their needs, and their participation in disaster risk management are central elements. The 2015–2030 Sendai Framework recommendations, recent disaster experiences and research have highlighted that new models can improve communication effectiveness. In this paper, we critically explore this transition by conducting a scoping review (n=109 publications) of seismic risk communication in Europe. We analyse the approaches, messages, tools, and channels used for seismic risk communication and how they have changed over time. The results reveal that the stated goals of seismic risk communication are, in decreasing order, to share information, raise awareness, change behaviours/beliefs, and increase preparedness. Pupils, students, and citizens are the primary recipients of communication activities. Over the years, two trends have emerged. First, “two-way”, transdisciplinary and bottom-up communication models prevailed over the “one-way” model. Second, communication aimed more at promoting proactive behaviours than just informing the public. Face-to-face, hands-on activities, and serious games are key tools to engage with the public. The results also reveal the emerging role of social media to target different audiences/social groups. Strikingly, only one-fifth of the analysed publications explicitly build on or tests risk communication theories. Future research could focus on comparing practices across countries and risks (e.g., earthquakes and floods) and on innovating communication theories and methodologies, especially by incorporating the role of information technologies and social media.
Mutational profiling of Chinese patients with thyroid cancer
Authors: Du Yaying , Zhang Shu , Zhang Gang , Hu Jiaying , Zhao Lianhua , Xiong Yuanyuan , Shen Lu , Chen Rongrong , Ye Ke , Xu Yan 
Published: July 2023

BackgroundThe incidence of thyroid cancer in China has rapidly increased in recent decades. As the genetic profiles of thyroid cancer vary dramatically between different geographical regions, a comprehensive genetic landscape of thyroid cancer in the Chinese population is urgently needed.MethodsWe retrospectively included thyroid cancer patients from three Chinese medical centers between February 2015 and August 2020. To dissect the genomic profiling of these patients, we performed targeted next-generation sequencing on their tumor tissues using a 1,021-gene panel.ResultsA total of 458 Chinese patients with thyroid cancer were enrolled, including four malignant histological subtypes arising from follicular epithelial thyroid cells. BRAF driver mutations were identified in 76.0% of patients, followed by RET rearrangements (7.6%) and RAS driver mutations (4.1%). Tumors with more somatic mutations correlated with worse clinical characteristics, including older age at diagnosis, less differentiation of tumor, larger tumor size, lymph node metastasis and distal metastasis. Subclonal BRAF mutations occurred in 20% (6/30) of patients and were frequent in poorly differentiated or anaplastic tumors (33.3% [2/6] vs. 4.2% [1/24], P = 0.09) and those with distal metastasis (50.0% [2/4] vs. 8.7% [2/23], P = 0.09). Tumors with TERT promoter mutations had significantly more somatic mutations (average: 6.5 vs. 1.8, P &lt; 0.001). Moreover, TERT promoter mutations were not associated with lymph node metastasis but significantly associated with older age at diagnosis and poorly differentiated or anaplastic tumors, regardless of their clonal architecture.ConclusionOur results shed light on the molecular pathogenesis and clinical characteristics of thyroid cancer in the Chinese population. The number of somatic mutations, TERT promoter mutations, and the clonal architecture of BRAF mutations should be considered in the risk stratification of thyroid cancer.
Immunogenomic profile at baseline predicts host susceptibility to clinical malaria
Authors: Mbambo Gillian , Dwivedi Ankit , Ifeonu Olukemi O. , Munro James B. , Shrestha Biraj , Bromley Robin E. , Hodges Theresa , Adkins Ricky S. , Kouriba Bourema , Diarra Issa , Niangaly Amadou , Kone Abdoulaye K. , Coulibaly Drissa , Traore Karim , Dolo Amagana , Thera Mahamadou A. , Laurens Matthew B. , Doumbo Ogobara K. , Plowe Christopher V. , Berry Andrea A. , Travassos Mark , Lyke Kirsten E. , Silva Joana C. 
Published: July 2023

IntroductionHost gene and protein expression impact susceptibility to clinical malaria, but the balance of immune cell populations, cytokines and genes that contributes to protection, remains incompletely understood. Little is known about the determinants of host susceptibility to clinical malaria at a time when acquired immunity is developing.MethodsWe analyzed peripheral blood mononuclear cells (PBMCs) collected from children who differed in susceptibility to clinical malaria, all from a small town in Mali. PBMCs were collected from children aged 4-6 years at the start, peak and end of the malaria season. We characterized the immune cell composition and cytokine secretion for a subset of 20 children per timepoint (10 children with no symptomatic malaria age-matched to 10 children with &gt;2 symptomatic malarial illnesses), and gene expression patterns for six children (three per cohort) per timepoint. ResultsWe observed differences between the two groups of children in the expression of genes related to cell death and inflammation; in particular, inflammatory genes such as CXCL10 and STAT1 and apoptotic genes such as XAF1 were upregulated in susceptible children before the transmission season began. We also noted higher frequency of HLA-DR+ CD4 T cells in protected children during the peak of the malaria season and comparable levels cytokine secretion after stimulation with malaria schizonts across all three time points. ConclusionThis study highlights the importance of baseline immune signatures in determining disease outcome. Our data suggests that differences in apoptotic and inflammatory gene expression patterns can serve as predictive markers of susceptibility to clinical malaria.
Comprehensive bioinformatics analysis reveals the crosstalk genes and immune relationship between the systemic lupus erythematosus and venous thromboembolism
Authors: Yu Jingfan , Yang Jian , He Qifan , Zhang Zhixuan , Xu Guoxiong 
Published: July 2023

BackgroundIt is well known that patients with systemic lupus erythematosus (SLE) had a high risk of venous thromboembolism (VTE). This study aimed to identify the crosstalk genes between SLE and VTE and explored their clinical value and molecular mechanism initially.MethodsWe downloaded microarray datasets of SLE and VTE from the Gene Expression Omnibus (GEO) dataset. Differential expression analysis was applied to identify the crosstalk genes (CGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the shared genes. The shared diagnostic biomarkers of the two diseases were further screened from CGs using least absolute shrinkage and selection operator (Lasso) regression. Two risk scores for SLE and VTE were constructed separately to predict the likelihood of illness according to the diagnostic biomarkers using a logical regression algorithm. The immune infiltration levels of SEL and VTE were estimated via the CIBERSORT algorithm and the relationship of CGs with immune cell infiltration was investigated. Finally, we explored potential phenotype subgroups in SLE and VTE based on the expression level of CGs through the consensus clustering method and studied immune cell infiltration in different subtypes.ResultA total of 171 CGs were obtained by the intersection of differentially expressed genes (DEGs) between SLE and VTE cohorts. The functional enrichment shown these CGs were mainly related to immune pathways. After screening by lasso regression, we found that three hub CGs (RSAD2, HSP90AB1, and FPR2) were the optimal shared diagnostic biomarkers for SLE and VTE. Based on the expression level of RSAD2 and HSP90AB1, two risk prediction models for SLE and VTE were built by multifactor logistic regression and systemically validated in internal and external validation datasets. The immune infiltration results revealed that CGs were highly correlated with multiple infiltrated immunocytes. Consensus clustering was used to respectively regroup SLE and VTE patients into C1 and C2 clusters based on the CGs expression profile. The levels of immune cell infiltration and immune activation were higher in C1 than in C2 subtypes.ConclusionIn our study, we further screen out diagnostic biomarkers from crosstalk genes SLE and VTE and built two risk scores. Our findings reveal a close relationship between CGs and the immune microenvironment of diseases. This provides clues for further exploring the common mechanism and interaction between the two diseases.
Reduning alleviates sepsis-induced acute lung injury by reducing apoptosis of pulmonary microvascular endothelial cells
Authors: Wang Ziyi , Guo Zhe , Wang Xuesong , Liao Haiyan , Chen Feng , Liu Yuxin , Wang Zhong 
Published: July 2023

IntroductionSepsis-induced acute lung injury (SALI) is a critical illness with high mortality, and pulmonary microvascular endothelial cells (PMECs) barrier dysfunction is a well-documented pathogenesis of SALI. The current study aimed to investigate the underlying mechanism of Reduning (RDN) in the treatment of SALI.MethodsNetwork pharmacology and molecular dynamics simulation (MDS) were used to confirm the possibility of key active components of RDN combining with AKT1. Hematoxylin-eosin staining (HE) and immunohistochemistry (IHC) were used to investigate the effect of RDN in vivo. Immunofluorescence (IF) and co-immunoprecipitation (CoIP) were used to investigate the relationship between mammalian target of rapamycin (mTOR) and Bax in PMECs. ELISA was used to test the level of TNF-α. Flow cytometry was used to detect apoptosis. JC-1 and electron microscopy were used to evaluate mitochondrial damage. The results showed that RDN likely alleviated SALI via targeting AKT1.ResultsIn vivo, RDN could evidently decrease the expression levels of apoptosis-related proteins, alleviate mitochondrial damage, reduce lung tissue edema, down-regulate the level of TNF-α in the serum, and improve the mortality of sepsis in mice. In vitro, RDN had a significant effect on reducing the level of apoptosis-related proteins and cell apoptosis rate, while also mitigated mitochondrial damage. Furthermore, RDN could effectively lower the level of Bax in PMECs and increase the level of mTOR both in vivo and in vitro. Notably, mTOR has the ability to directly bind to Bax, and RDN can enhance this binding capability.DiscussionRDN could attenuate SALI through reducing apoptosis of PMECs, which is a promising therapeutic strategy for SALI prevention.
Causal association between inflammatory bowel disease and herpes virus infections: a two-sample bidirectional Mendelian randomization study
Authors: Zou Menglong , Zhang Wei , Shen Lele , Xu Yin , Zhu Ying 
Published: July 2023

BackgroundPrevious observational or retrospective studies have suggested an association between inflammatory bowel disease (IBD) and herpes virus infections. Using Mendelian randomization (MR) approach, our objective was to determine whether there was a causal association between IBD and herpes virus infections.MethodsIn genome-wide association study (GWAS) datasets of the International Inflammatory Bowel Disease Genetics Consortium, we obtained genetic instrumental variables for three phenotypes from 34,652 participants (12,882 IBD cases and 21,770 controls), 27,432 participants [6,968 ulcerative colitis (UC) cases and 20,464 controls], and 20,883 participants [5,956 Crohn’s disease (CD) cases and 14,927 controls], respectively. Summary statistics for herpes virus infections (chickenpox, herpes zoster, and mononucleosis) were obtained from the FinnGen database. MR results were expressed as odds ratio (OR) with 95% confidence interval (CI).ResultsOur study found no evidence of a causal effect of genetically predicted IBD on herpes virus infections [P value for inverse variance weighting (IVW): 0.063 to 0.652]. For the subtypes of IBD, UC had a suggestive association with mononucleosis (P value for IVW: 0.023). It appeared that CD was also weakly associated with mononucleosis (P value for IVW: 0.058; P value for Weighted median: 0.036). In addition, we found a suggestive causality for CD on chickenpox (P value for IVW: 0.038). Neither UC (P value for IVW: 0.574) nor CD (P value for IVW: 0.168) has a causal effect on herpes zoster. The results of the bidirectional MR analysis did not indicate that herpes virus infections were associated with IBD, UC or CD (P value for IVW: 0.239 to 0.888).ConclusionThis study showed a suggestive causality for both CD-chickenpox and UC-mononucleosis, despite no associations reaching a statistical significance value after corrections for multiple testing. There was no evidence of a causal association between IBD and its two subtypes on herpes zoster.
Dose–response study of prophylactic nitroglycerin for prevention of pituitrin-induced hypertension during laparoscopic myomectomy: a prospective, randomized study
Authors: Wang Jin , Xu Qiang , Xiao Fei , Chen Gang 
Published: July 2023

ObjectiveTo determine the dose–response of nitroglycerin in preventing pituitrin-induced hypertension in patients undergoing laparoscopic myomectomy.MethodsHundred patients scheduled for elective laparoscopic myomectomy were randomly allocated into one of five groups (n = 20) to receive intravenous bolus of prophylactic nitroglycerin at 0, 50, 75, 100, and 125 μg one minute following administration of 3 IU of pituitrin into the myometrium. The patients were monitored for pituitrin-induced hypertension with the primary outcome to determine the effective dose of prophylactic nitroglycerin, defined as complete prevention of pituitrin-induced hypertension during the study period. Probit analysis was used to calculate the median effective dose (ED50) and 95% effective dose (ED95) of prophylactic nitroglycerin.ResultsHypertension occurred in 19/20, 10/20, 8/20, 2/20, and 1/20 in patients who received 0, 50, 75, 100, and 125 ug of prophylactic nitroglycerin, respectively. The calculated ED50 and ED95 of nitroglycerin for preventing hypertension were 54 μg (95%CI: 35~66 μg) and 136 μg (95%CI: 105~289 μg).ConclusionA prophylactic bolus of nitroglycerin administered immediately following injection of pituitrin into the myometrium during laparoscopic myomectomy effectively prevented pituitrin-induced hypertension, with the ED50 and ED95 of 54 μg and 136 μg, respectively. This information would be useful for clinical practice.Clinical trial registrationwww.chictr.org.cn, Identifier ChiCTR2200062282.
Anti-Cryptosporidium parvum activity of Artemisia judaica L. and its fractions: in vitro and in vivo assays
Authors: Ahmed Shahira A. , Eltamany Enas E. , Nafie Mohamed S. , Elhady Sameh S. , Karanis Panagiotis , Mokhtar Amira B. 
Published: July 2023

BackgroundThis study investigates the toxic activity ofArtemisia judaicaethanolic extract (ArEx) as well as its phenolic fraction (ArPh), and terpenoid fraction (ArT) againstCryptosporidium parvum(C. parvum) oocysts.MethodsOver a 4 months period, estimation of the total phenolic (TPC), total flavonoids (TFC), and total terpenoids contents (TTC) in ArEx; investigation of thein vitroantioxidant activity of ArEx, ArPh, and ArT; evaluation of ArEx, ArPh, and ArT toxic activity againstC. parvumoocysts using MTT assay; parasitological analysis on ArPh-treatedC. parvumoocysts and comet assay were performed bothin vitroandin vivo(infectivity).ResultsThe ArEx TPC, TFC, and TTC was 52.6 ± 3.1 mgGAE/g, 64.5 ± 3.1 mg QE/g, and 9.5 ± 1.1 mg Linol/g, respectively. Regarding the phytochemicalin vitroantioxidant activity, the ArPh exhibited the highest antioxidant activity compared to the ArEx and ArT. The ArPh showed promising free radical scavenging activity of DPPH and ABTS•+with IC50values of 47.27 ± 1.86 μg/mL and 66.89 ± 1.94 μg/mL, respectively. Moreover, the FRAP of ArPh was 2.97 ± 0.65 mMol Fe+2/g while its TAC was 46.23 ± 3.15 mg GAE/g. The ArPh demonstrated toxic activity againstC. parvumoocysts with a potent IC50value of 31.6 μg/mL compared to ArT (promising) and ArEx (non-effective). ArPh parasitological analysis demonstrated MIC90at 1000 μg/ml and effective oocysts destruction on count and morphology. ArPh fragmented oocysts nuclear DNA in comet assay. Beginning at 200 μg/mL, ArPh-treated oocysts did not infect mice.ConclusionTo combatC. parvuminfection, the phenolic fraction ofA. judaicaL. shows promise as an adjuvant therapy or as a source of potentially useful lead structures for drug discovery.
Development and bioassessment of high nutria-omega 5 cookies through animal modeling
Authors: Iqbal Nida , Shabbir Muhammad Asim , Khan Moazzam Rafiq , Faisal Muhammad Naeem 
Published: July 2023

The food industry generates a diverse range of waste byproducts during fruit processing, which can be repurposed to create functional foods and other valuable commodities. In this particular study, leftover agro-waste from pomegranate juice was valorized to obtain pomegranate seed oil (PSO), while utilizing sunflower oilseed cake to produce sunflower meal protein concentrate (SMPC). These two extracted components were then combined as ingredients to produce High Nutria Omega 5 (HNO5) cookies. To ensure the quality and viability of pomegranate seed oil, a comprehensive set of laboratory analytical procedures were employed to evaluate its characteristics. Subsequently, different ratios of pomegranate seed oil and sunflower meal protein concentrate were utilized to develop the HNO5 cookie products. These cookies underwent thorough sensory, physicochemical, storage, and proximate evaluations as well as efficacy studies to assess their overall nutritional quality and shelf-life properties. As compared to the control feed, the findings of the renal and liver functional tests indicated a favorable effect on ALT, AST, ALP, serum urea, creatinine, albumin, globulins, total proteins, and A/G ratio. The results revealed that PSO and SMPC cookies containing 15% PSO and 15% SMPC exhibited stability in numerous physicochemical and sensory assessments. The punicic acid in HNO5 cookies significantly reduced the effects of starvation in rats and progressively improved several metabolic processes and overall health profiles.Graphical Abstract