bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatocyte growth factor and B-type natriuretic peptide as independent predictors of mortality in HFpEF patients
Authors: Chen Hou-liang , Zhu Xue-tao , Zhang Wang , Cheng Xiao-bing , Hu Ze-ping 
Published: February 2025

BackgroundHeart failure with preserved ejection fraction (HFpEF) is a common and heterogeneous syndrome with high mortality and morbidity. However, few studies have evaluated the relationship between biomarkers and subsequent outcomes in HFpEF patients.ObjectiveTo assess the association between plasma hepatocyte growth factor (HGF) levels and all-cause mortality in HFpEF patients.MethodsThis was a retrospective cohort study of 412 HFpEF patients who were hospitalized in the Department of Cardiology of the First Affiliated Hospital of Anhui Medical University from November 2020 to November 2021. The patients were divided into two groups according to the 24-month follow-up results: deceased (82 cases) and survivors (330 cases). The primary outcome was all-cause mortality. Multivariate logistic regression analysis was performed to identify the risk factors for all-cause mortality in HFpEF patients. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value of relevant indicators for HFpEF mortality risk. Kaplan–Meier analysis was used to assess the risk of all-cause mortality in patients with increased relevant indicators.ResultsMultivariate logistic regression analysis showed that HGF, B-type natriuretic peptide precursor (BNP), total protein (TP), estimated glomerular filtration rate (eGFR), and tetraiodothyronine (T4) were independent risk factors for all-cause mortality in HFpEF patients (P &lt; 0.05). ROC curve analysis showed that the optimal cut-off point of HGF was 1,598 pg/ml [area under the curve (AUC) = 0.645, P = 0.000, hazard ratio (HR) = 3.186, 95% confidence interval (CI): 1.963–5.171], the optimal cut-off point of BNP was 271 pg/ml (AUC = 0.703, P &lt; 0.000, HR = 4.494, 95% CI: 2.914–6.930), and the optimal cut-off point of eGFR was 114.5 ml/min/1.73 m2 (AUC = 0.644, P = 0.423). Kaplan–Meier survival curve analysis showed that the survival probability of the patients with low HGF and BNP concentrations was significantly higher (P &lt; 0.0001), while there was no significant difference in the survival rate between the two subgroups with eGFR as the cut-off value (P = 0.423).ConclusionHGF and BNP are independent risk factors for all-cause mortality events in HFpEF patients during 24 months of follow-up, and the survival probability of HFpEF patients with low HGF and BNP concentrations is higher.
Analysis of mutations in mitochondrial transfer RNA genes and the maternal inheritance of polycystic ovary syndrome
Authors: Nawaz Tanzeela , Awan Tahira , Zahoor Humaira , Gul Romana , Bibi Shaheen , Uddin Aziz , Abbas Ghulam , Ghafoor Sajid Ul , Belay Sefealem Assefa , Rehman Abdur , Li Xing-Guo , Tabassum Saadia 
Published: February 2025

IntroductionPolycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. Despite the escalating global prevalence, there is currently no definitive predisposition test available for this condition. Among the genetic causes, variations in the mitochondrial DNA (mtDNA) are increasingly recognized as a crucial contributor to the development of PCOS. However, cross-ethnic analysis of these mutations is lacking. To fill in this gap, our objective is to identify new maternal genetic risk factors associated with PCOS by investigating the mitochondrial transfer RNA (mt-tRNA) genes in PCOS patients from Pakistan and to compare these mutations to those in patients from other ethnic groups.MethodsDNA was extracted from saliva samples of patients. Primers were designed for the amplification of all of 22 mt-tRNA genes, and PCR was employed under defined conditions. Subsequently, Sanger sequencing was employed to decipher the sequences of mt-tRNA genes. Following sequencing, mt-tRNA genes underwent mutation analysis. Finally, we utilized MitoTIP (Mitochondrial tRNA Informatics Predictor) to identify variations in mt-tRNA genes.ResultsIn a cohort of 64 Pakistani patients with PCOS, our analysis unveiled eight variants in five mt-tRNA genes including MT-TH, MT-TL2, MT-TS1, MT-TS2, and MT-TT genes. All of these variants have not been previously reported in PCOS except one we have recently identified in a Pakistani patient with PCOS. Interestingly, most of these mt-tRNA genes carry variants found in patients with PCOS across distinct ethnic groups. Furthermore, these mutations occurred in highly conserved nucleotides of tRNA, essential for ensuring the stability and biochemical functionality of mt-tRNA. Finally, the pathogenic potential of these variations was assessed by in silico analysis. The pathogenicity prediction of these variants suggests their potential impact on mitochondrial dysfunction that was responsible for the clinical phenotypes of PCOS.ConclusionOur study identified novel variations in mt-tRNA genes in Pakistani women with PCOS. To our knowledge, this is the first report comparing mutations of mt-tRNA genes in PCOS patients across different ethnic groups. Our data revealed common mt-tRNA genes carrying PCOS-associated mutations that may be specific to certain ethnic populations. Together, our work provides new insights into the role of mt-tRNA genes in mitochondrial dysfunction underlying the pathophysiology of PCOS, highlighting mt-tRNA mutations as potential factors for future predisposition tests and more effective therapies for this globally prevalent condition.
Large copy number variants are an important cause of congenital hyperinsulinism that should be screened for during routine testing
Authors: Flanagan Sarah E. , Lazaridi Isabella-Anna , Männistö Jonna M. E. , Bennett Jasmin J. , Kalyon Oguzhan , Johnson Matthew B. , Wakeling Matthew N. , Houghton Jayne A. L. , Laver Thomas W. 
Published: February 2025

IntroductionCongenital hyperinsulinism (HI) is characterized by inappropriate insulin secretion from the pancreatic beta-cells which causes severe hypoglycemia. Copy number variants (CNVs) encompassing multiple genes (contiguous gene CNVs) can cause syndromic forms of HI although they are not typically screened for during routine genetic testing for this condition. We aimed to assess the prevalence of disease-causing contiguous gene CNVs in a cohort of individuals referred for HI genetic testing.MethodsOur cohort consisted of 3,763 individuals, of which 1,916 had received a genetic diagnosis for their HI and 1,847 were genetically unsolved following routine testing. We screened for 6 different contiguous gene CNVs using next-generation sequencing data from all individuals in the genetically unsolved cohort and searched for patients in our solved cohort who had already been found to have one of these CNVs.ResultsWe identified a contiguous gene CNV affecting 5 of the 6 genomic loci in 53 probands; 28 from the solved cohort and 25 from the genetically unsolved cohort. Variants on the X chromosome were most common, being detected in 24/53 children. Overall, these variants represented 2.7% (53/1,941) of genetic diagnoses, which is similar to the prevalence of variants in other commonly screened HI genes.DiscussionThese results confirm that contiguous gene CNVs are an important cause of HI which should be included in standard gene panel testing processes as this will improve pick-up rates for genetic diagnoses in HI.
Identification of cancer-associated fibroblast signature genes for prognostic prediction in colorectal cancer
Authors: Jin Wei , Lu Yuchang , Lu Jingen , Wang Zhenyi , Yan Yixin , Liang Biao , Qian Shiwei , Ni Jiachun , Yang Yiheng , Huang Shuo , Han Changpeng , Yang Haojie 
Published: February 2025

BackgroundCancer-associated fibroblasts are an essential part of the tumor immunoenvironment, playing key roles in malignancy progression and treatment response. This study was to characterize cancer-associated fibroblasts-related genes (CAFs) in colorectal cancer (CRC) and establish signature genes associated with CAF for prognosis prediction.MethodsWe downloaded single-cell RNA sequencing (scRNA-seq) data from the GEO database and bulk RNA-seq data from TCGA database to identify differentially expressed genes related to fibroblasts. In the TCGA set, DEGs were identified from tumor samples, and the WGCNA method was utilized to identify module genes. By comparing the WGCNA module genes with tumor fibroblast-related DEGs, we took the overlapped cohorts as crucial CAFs. Moreover, the prognostic CAFs were identified using univariate analysis. A CAFs risk model was established using the LASSO algorithm and then validated using external datasets. Ultimately, the expression of prognostic CAFs in CRC was confirmed using qRT-PCR.ResultsA large cohort of DEGs were identified as CAFs, with eight demonstrating prognostic significance. These CAFs were primarily related to seven pathways, including peroxisome function, B cell receptor signal, and cell adhesion molecule. The CAFs risk model exhibited high accuracy for predicting prognosis, as confirmed through validation using external independent cohorts. Additionally, the risk signature showed significant correlations with immune-related scores, tumor purity, estimate, and stromal scores. qRT-PCR validated that the expression level of RAB36 was significantly downregulated in the HCT116 and HT29 cell lines compared to the NCM460 cells. Conversely, CD177, PBX4 and CCDC78 were upregulated in the HCT116 and HT29 cell lines, and ACSL6 and KCNJ14 only in HCT116 cells (P &lt; 0.05). The expression trends of CD177 and CCDC78 were consistent with our predicted results.ConclusionThe CAFs risk model accurately predicted prognosis, immune cell infiltration, and stromal estimates. The prognostic CAFs (CD177 and CCDC78) may be potential therapeutic targets for CRC.
Pattern of dermatoses in Wolaita zone prison setting: a call for improved dermatology services
Authors: Kelbore Abraham Getachew , Bogino Efa Ambaw , Morrone Aldo 
Published: February 2025

BackgroundSkin diseases are not uncommon among prisoners, primarily due to confined living conditions, limited access to proper hygiene facilities, and higher rates of skin-to-skin contact. The study aims to describe the skin disease spectrum among prison inmates Wolaita zone, southern Ethiopia.MethodsA cross-sectional study was conducted at the Wolaita zone prison to determine the spectrum of skin diseases among the prison inmates from January 1 to February 30, 2020. Every inmate with skin complaints underwent a comprehensive skin examination, and a detailed history of their skin-compliant was documented. The diagnosis primarily relied on clinical assessment by dermatologists. The data collected from paper-based abstraction sheets was entered into EpiData entry forms twice to ensure accuracy. A descriptive analysis was performed such as frequencies, mean, standard deviation and median. The statistical significance was set at 0.05.ResultOut of the 418 prison inmates who took part in the study, 223 (53.3%) were found to have skin disorders. The vast majority of the participants, specifically 381 (91.1%), were male. The age range of the participants varied from 17 to 60 years old, with an average age of 29.29 years ± 9.08 years. Skin infections were identified as the most prevalent type of skin disease, with 113 patients (50.67%) affected. Among the skin infections, fungal infections and scabies infestations were the most common, accounting for 41 cases (18.4%) and 37 cases (8.85%) respectively. In terms of inflammatory skin problems, 50 cases (11.9%) of Eczematous skin diseases were diagnosed. Within this category, Atopic Eczema and Nummular eczema accounted for 19 (4.5%) and 8 (1.9%) cases, respectively. Notably, a case of Leprosy was also diagnosed and linked to treatment within this prison.ConclusionIn this study, infectious skin diseases and manageable inflammatory skin diseases are commonly diagnosed as dermatoses among prison inmates at Wolaita zone Prison. The inmates have the right to the best of health, including skin health, so health professionals posted to prison services must be trained to diagnose and manage skin disorders in prisons.
High-resolution 3D visualization of human hearts with emphases on the cardiac conduction system components—a new platform for medical education, mix/virtual reality, computational simulation
Authors: Chen Weixuan , Kuniewicz Marcin , Aminu Abimbola J. , Karaesmen Irem , Duong Neal , Proniewska Klaudia , van Dam Peter , Iles Tinen L. , Hołda Mateusz K. , Walocha Jerzy , Iaizzo Paul A. , Colman Michael A. , Dobrzynski Halina , Atkinson Andrew J. 
Published: February 2025

IntroductionHigh-resolution digitized cardiac anatomical data sets are in huge demand in clinical, basic research and computational settings. They can be leveraged to evaluate intricate anatomical and structural changes in disease pathology, such as myocardial infarction (MI), which is one of the most common causes of heart failure and death. Advancements in high-resolution imaging and anatomical techniques in this field and our laboratory have led to vast improvements in understanding cardiovascular anatomy, especially the cardiac conduction system (CCS) responsible for the electricity of the heart, in healthy/aged/obese post-mortem human hearts. However, the digitized anatomy of the electrical system of the heart within MI hearts remains unexplored.MethodsFive post-mortem non-MI and MI human hearts were obtained by the Visible Heart® Laboratories via LifeSource, Minneapolis, MN, United States (with appropriate ethics and consent): specimens were then transported to Manchester University with an material transfer agreement in place and stored under the HTA 2004, UK. After performing contrast-enhanced micro-CT, a visualization tool (namely Amira) was used for 3D high-resolution anatomical visualizations and reconstruction. Various cardiovascular structures were segmented based on the attenuation difference of micro-CT scans and tissue traceability. The relationship between the CCS and surrounding tissues in MI and non-MI human hearts was obtained. 3D anatomical models were further explored for their use in computational simulations, 3D printing and mix/virtual reality visualization.Results3D segmented cardiovascular structures in the MI hearts elicited diverse macro-/micro- anatomical changes. The key findings are thickened valve leaflets, formation of new coronary arteries, increased or reduced thicknesses of pectinate and papillary muscles and Purkinje fibers, thinner left bundle branches, sinoatrial nodal atrophy, atrioventricular conduction axis fragmentation, and increased epicardial fat in some hearts. The propagation of the excitation impulses can be simulated, and 3D printing can be utilized from the reconstructed and segmented structures.DiscussionHigh-resolution digitized cardiac anatomical datasets offer exciting new tools for medical education, clinical applications, and computational simulation.
Myocardial injury in spontaneous intracerebral hemorrhage is not predicted by prior cardiac disease or neurological status: results from the Mannheim Stroke database
Authors: Lesch Hendrik , Haucke Lea , Kruska Mathieu , Ebert Anne , Becker Louisa , Szabo Kristina , Akin Ibrahim , Alonso Angelika , Fastner Christian 
Published: February 2025

Background and aimsElevated cardiac troponin (cTn) levels (representing myocardial injury) are frequently found in patients with spontaneous intracerebral hemorrhage (sICH). Overall, the relationship between sICH and elevated cTn levels is not well understood. The aim of this study was to investigate patient characteristics and clinical parameters in patients with sICH and myocardial injury.MethodsThis is a retrospective observational study based on the Mannheim Stroke database. Consecutive patient cases with acute symptomatic sICH and available high-sensitivity cTn I (hs-cTnI) at hospital admission between 2015 and 2021 were included. Group comparisons of patient, clinical and imaging characteristics were performed between groups with and without hs-cTnI elevation. In addition, variables with suspected predictive clinical significance for hs-cTnI elevation were analyzed for their predictive value using multivariate logistic regression analysis.ResultsA total of 93/498 patients with sICH (18.7%; mean age 73 ± 15 years; 51.9% females) had a hs-cTnI elevation. These patients did not have a more pronounced cerebrovascular risk profile and had a comparably low prevalence of coronary artery disease (18.5%, p = NS) compared to those without elevated hs-cTnI levels. Elevated hs-cTnI levels had no impact on in-hospital mortality (21.5 vs. 20.5%, p = NS) or functional outcome at discharge. Solely clinically relevant aortic valve stenosis, graded as moderate or higher, independently predicted hs-cTnI elevation (p &lt; 0.003). Other cardiac preconditions or neurological functional parameters did not serve as significant predictors.ConclusionsMyocardial injury is common in patients with sICH. Unlike in AIS patients, elevated hs-cTnI levels were not associated with a worse functional or mortality-related in-hospital outcome. Except for clinically relevant aortic valve stenosis, structural heart disease had no significant influence as a predictor. We therefore suggest that hs-cTnI elevation in patients with sICH is related to acute myocardial damage along the brain-heart axis.
Trametinib as a targeted treatment in cardiac and lymphatic presentations of Noonan syndrome
Authors: De Brouchoven Isabel , Lorand Juan , Bofferding Léon , Sorlin Arthur , Van Damme An , Danhaive Olivier 
Published: February 2025

IntroductionRare pathogenic variants in the PTPN11, KRAS, SOS1 and RAF1 genes are the main molecular causes of Noonan syndrome (NS). Most are dominant gain-of-function variants that cause an overactivation of the RAS/MAPK signaling pathway leading to uncontrolled cell proliferation in many organs and systems. Albeit phenotypically heterogeneous, NS can be associated with severe cardiovascular and lymphatic anomalies, potentially lethal during infancy, neonatal and fetal periods. MEK inhibitors, a class of drugs targeting the final steps of the RAS/MAPK pathway and originally developed for cancer therapy, have been tested in preclinical studies as a targeted treatment for NS. These studies led to the occasional off-label use of MEK inhibitors in patients with RASopathies.MethodsWe report the case of a preterm infant with congenital pulmonary lymphangiectasis, chylothorax and hypoxic respiratory failure refractory to conventional management, who was treated with trametinib after identification of a NS PTPN11 class 5 variant. We performed a systematic review of the current published evidence on trametinib efficacy and safety for severe respiratory and/or cardiac manifestations in infants and children with Noonan syndrome, querying PubMed, Embase, Cochrane and Scopus databases, following the PRISMA guideline for systematic reviews, and using the Joanna Briggs Institute (JBI) Critical Appraisal tool for quality assessment of published evidence.ResultsIn our patient, a five-week trametinib course, maximum dose 0.025 mg/kg/day, led to chylothorax resolution and gradual pulmonary function improvement, allowing extubation to non-invasive support, discharge home at a corrected age of 4 months, and weaning off home oxygen therapy by 10 months. No formal clinical trial of trametinib in neonatal/pediatric Noonan syndrome has been published to our knowledge. We collected 16 published cases, and added this case for reviewing trametinib regimen, efficacy and safety. A short-term improvement of symptoms was reported in all cases, with three deaths presumably unrelated to trametinib. Moderate side effects were reported in a subset of patients. Long-term follow-up data were not available.DiscussionTrametinib is a promising drug in NS. Clinical trials are warranted to establish safety, efficacy, and standardized protocols for the use of trametinib as a rescue therapy in critically ill children and explore its potential place in the treatment of various NS comorbidities.Systematic Review Registrationclinicaltrials.gov, identifier [NCT06555237].
Association of prenatal trajectories of depressive and anxiety symptoms with neurodevelopment of children aged 0-24 months: A prospective study
Authors: Chen Ruoqing , Liu Weiying , Wu Feng , Ye Xiaomin , Wang Xuanshu , Zheng Yeqi , Tan Weiri , Ding Ruyi , Liu Mengting , Gao Yi , Liang Hui , Zhang Quanfu , Fang Fang , Yu Yan , Chen Xu , Ma Liya 
Published: February 2025

BackgroundPrenatal depression and anxiety can significantly impact a child’s neurodevelopment. However, the specific timing and patterns of these maternal psychological symptoms during pregnancy that influence the child’s neurodevelopment remain unclear. This study aimed to investigate the associations of maternal depressive and anxiety symptoms across pregnancy trimesters and their trajectories with neurodevelopmental outcomes in children aged 0 to 24 months.MethodsA total of 16,229 singletons born between January 2020 and December 2023 were included in this prospective study. Maternal depressive and anxiety symptoms in each trimester of pregnancy were assessed by Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7 scale, respectively. The neurodevelopmental status of children aged 0-24 months was assessed by the Ages and Stages Questionnaire-Third Edition. Group-based trajectory model was employed to identify distinct trajectories of prenatal depressive and anxiety symptoms throughout pregnancy. Poisson regression was used to assess the associations of maternal depressive and anxiety symptoms, as well as their trajectories, with the child’s neurodevelopment.ResultsA total of 1,791 (11.04%) children had neurodevelopmental delay in the communication domain, 1,127 (6.94%) in the gross motor domain, 1,750 (10.78%) in the fine motor domain, 1,137 (7.01%) in the problem-solving domain, and 1,724 (10.62%) in the personal-social domain. Maternal depressive and anxiety symptoms during pregnancy, especially in the second and third trimester, were associated with a higher risk of neurodevelopmental delay in all domains, with the most profound impact observed in the fine motor domain. Four trajectories were identified for prenatal depressive and anxiety symptoms, respectively. Compared with children whose mothers had low level of depressive or anxiety symptoms throughout pregnancy, children whose mothers experienced consistently moderate or high level of these symptoms had a higher risk of neurodevelopmental delay, while children whose mothers experienced moderate level of depressive or anxiety symptoms that decreased to low levels after the first trimester did not show a different risk of neurodevelopmental delay.ConclusionMaternal depressive and anxiety symptoms during pregnancy have an adverse impact on the neurodevelopment in offspring. This study highlights the importance of improving the mental health of pregnant women in order to support optimal neurodevelopment for their children.