bluuebunny/crossref_metadata_2025 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

Background

Heart 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.

Objective

To assess the association between plasma hepatocyte growth factor (HGF) levels and all-cause mortality in HFpEF patients.

Methods

This 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.

Results

Multivariate 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 < 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 < 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 < 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).

Conclusion

HGF 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

Introduction

Polycystic 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.

Methods

DNA 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.

Results

In 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.

Conclusion

Our 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

Introduction

Congenital 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.

Methods

Our 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.

Results

We 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.

Discussion

These 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

Background

Cancer-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.

Methods

We 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.

Results

A 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 < 0.05). The expression trends of CD177 and CCDC78 were consistent with our predicted results.

Conclusion

The 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.
Can invariant Natural Killer T cells drive B cell fate? a look at the humoral response
Authors: Palacios Pablo A. , Santibañez Álvaro , Aguirre-Muñoz Fernanda , Gutiérrez-Vera Cristián , Niño de Zepeda-Carrizo Valentina , Góngora-Pimentel Martín , Müller Marioly , Cáceres Mónica , Kalergis Alexis M. , Carreño Leandro J.
Published: February 2025

Invariant Natural Killer T (NKT) cells represent a unique subset of innate-like T cells that express both NK cell and T cell receptors. These cells are rapidly activated by glycolipid antigens presented via CD1d molecules on antigen-presenting cells (APCs), including B cells, dendritic cells (DCs), and macrophages, or through cytokine-dependent mechanisms. Their ability to produce a wide range of cytokines and express costimulatory molecules underscores their critical role in bridging innate and adaptive immunity. B cells, traditionally recognized for their role in antibody production, also act as potent APCs due to their high expression of CD1d, enabling direct interactions with iNKT cells. This interaction has significant implications for humoral immunity, influencing B cell activation, class-switch recombination (CSR), germinal center formation, and memory B cell differentiation, thus expanding the conventional paradigm of T cell–B cell interactions. While the influence of iNKT cells on B cell biology and humoral responses is well-supported, many aspects of their interaction remain unresolved. Key questions include the roles of different iNKT cell subsets, the diversity of APCs, the spatiotemporal dynamics of these interactions, especially during early activation, and the potential for distinct glycolipid ligands to modulate immune outcomes. Understanding these factors could provide valuable insights into how iNKT cells regulate B cell-mediated immunity and offer opportunities to harness these interactions in immunotherapeutic applications, such as vaccine development. In this review, we examine these unresolved aspects and propose a novel perspective on the regulatory potential of iNKT cells in humoral immunity, emphasizing their promise as a target for innovative vaccine strategies.
Polyamine metabolism and anti-tumor immunity
Authors: Wu Jing-Yi , Zeng Yan , You Yu-Yang , Chen Qi-Yue
Published: February 2025

Growing attention has been directed toward the critical role of polyamines in the tumor microenvironment and immune regulation. Polyamines, primarily comprising putrescine, spermidine, and spermine, are tightly regulated through coordinated biosynthesis, catabolism, and transport, with distinct metabolic patterns between normal and cancerous tissues. Emerging evidence highlights the pivotal role of polyamine metabolism in tumor initiation, progression, and metastasis. This review aims to elucidate the differences in polyamine biosynthesis, transport, and catabolism between normal and cancerous tissues, as well as the associated alterations in tumor epigenetic modifications and resistance to immune checkpoint blockade driven by polyamine metabolism. Polyamine metabolism influences both tumor cells and the tumor microenvironment by modulating immune cell phenotypes—shifting them towards either tumor suppression or immune evasion within the tumor immune microenvironment. Additionally, polyamine metabolism impacts immunotherapy through its regulation of key enzymes. This review also explores potential therapeutic targets and summarizes the roles of polyamine inhibitors in combination with immunotherapy for cancer treatment, offering a novel perspective on therapeutic strategies.
Harnessing adjuvant-induced epigenetic modulation for enhanced immunity in vaccines and cancer therapy
Authors: Megdiche Yasmine , Salerno-Gonçalves Rosângela
Published: February 2025

Adjuvants are crucial in vaccines and cancer therapies, enhancing therapeutic efficacy through diverse mechanisms. In vaccines, adjuvants are traditionally valued for amplifying immune responses, ensuring robust and long-lasting protection against pathogens. In cancer treatments, adjuvants can boost the effectiveness of chemotherapy or immunotherapy by targeting tumor antigens, rendering cancer cells more vulnerable to treatment. Recent research has uncovered new molecular-level effects of the adjuvants, mainly through epigenetic mechanisms. Epigenetics encompasses heritable modifications in gene expression that do not alter the DNA sequence, impacting processes such as DNA methylation, histone modification, and non-coding RNA expression. These epigenetic changes play a pivotal role in regulating gene activity, influencing immune pathways, and modulating the strength and duration of immune responses. Whether in vaccines or cancer treatments, understanding how adjuvants interact with epigenetic regulators offers significant potential for developing more precise, cell-targeted therapies across various medical fields. This review delves into the evolving role of adjuvants and their interactions with epigenetic mechanisms. It also examines the potential of harnessing epigenetic changes to enhance adjuvant efficacy and explores the novel use of epigenetic inhibitors as adjuvants in therapeutic settings.
‘Horses for courses’ – an interrogation of tools for marine ecosystem-based management
Authors: Papadopoulou Nadia , Smith Christopher John , Franco Anita , Elliott Michael , Borja Angel , Andersen Jesper H. , Amorim Eva , Atkins Jon P. , Barnard Steve , Berg Torsten , Birchenough Silvana N. R. , Burdon Daryl , Claudet Joachim , Cormier Roland , Galparsoro Ibon , Judd Adrian , Katsanevakis Stelios , Korpinen Samuli , Lazar Luminita , Loiseau Charles , Lynam Christopher , Menchaca Iratxe , O’Toole Christina , Pedreschi Debbi , Piet Gerjan , Reid Dave , Salinas-Akhmadeeva Irene Antonina , Stelzenmüller Vanessa , Tamis Jacqueline E. , Uusitalo Laura , Uyarra Maria C.
Published: February 2025

Marine Ecosystem-Based Management (EBM) approaches are a well-established and fundamental component of international agreements and treaties, regional seas conventions, assessment strategies, European Directives and national and regional instruments. However, there is the need to interrogate and clarify the implementation of EBM approaches under current marine management. Although particular focus here is within the European Union Marine Strategy Framework Directive (MSFD), all lessons learned are applicable to marine assessments and management in seas worldwide given that all marine management instruments aim to ensure sustainability in marine ecosystems and human uses. Notably, the MSFD aims to ensure that Good Environmental Status (GES) will be achieved thereby enabling the sustainability of coastal and marine ecosystems to deliver ecosystem services and societal goods and benefits while at the same time being adaptive to rapid climate and environmental changes. As a clear understanding of EBM and the tools available to achieve it is needed for practitioners, regulators and their advisors, the analysis here firstly presents the current understanding of EBM (including its origin and application) and the wider 26 principles on which it is based. Secondly, we identify the key elements that are addressed by those principles (18 key EBM elements). Thirdly, we identify the types of tools available for use in the EBM context (19 tool groups). Fourthly we analyze the suitability of tool types to deliver the key EBM elements using an expert judgement approach. Finally, we conclude with the lessons learned from the use of those tools and briefly indicate how they could be combined to help achieve EBM in the most effective way. It is emphasized that no single tool is likely to satisfy all aspects of EBM and therefore employing a complementary suite of tools as part of a toolbox is recommended.
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

Background

Skin 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.

Methods

A 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.

Result

Out 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.

Conclusion

In 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

Introduction

High-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.

Methods

Five 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.

Results

3D 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.

Discussion

High-resolution digitized cardiac anatomical datasets offer exciting new tools for medical education, clinical applications, and computational simulation.
Impact of fasting and refeeding on immune markers, hepatic gene expression, and gut microbiota in geese: insights into metabolic regulation and gut-liver interactions
Authors: Liu Yi , Li Guangquan , Wang Xianze , Jia Huiyan , Dai Jiuli , Chen Shufang , He Daqian
Published: February 2025

Fasting and refeeding protocols, which induce short-term fluctuations in nutrient and energy levels, elicit adaptive physiological responses in animals. In this study, biochemical, transcriptome and 16S rRNA sequencing techniques were used to investigate the physiological effects of fasting and refeeding on immune responses, liver gene expression, and gut microbiota composition in geese. Fasting led to a significant reduction in circulating levels of IgA and IFN-γ, while IgG, TNF-α, IL-6, and IL-10 levels remained stable. Upon refeeding, IgA and IFN-γlevels rapidly returned to baseline. RNA-Seq analysis identified 858 differentially expressed genes (DEGs) between the control and fasted groups, and 732 DEGs between the fasted and refed groups. Key regulatory genes involved in energy metabolism and lipid biosynthesis, such as CPT1A, HMGCS1, and PCK1, were upregulated during fasting, reflecting an increase in fatty acid oxidation and gluconeogenesis. Conversely, lipogenic genes, including FASN, ACSS2, ACCα, and SCD, were downregulated during fasting and upregulated during refeeding, indicating a metabolic shift from catabolic to anabolic processes. Gene Ontology (GO) and KEGG pathway enrichment analyses revealed significant involvement of the PPAR signaling, glycolysis/gluconeogenesis, and insulin signaling pathways. Additionally, 16S rRNA gene sequencing indicated that fasting increased the abundance of Bacteroidetes and Proteobacteria, while decreasing Firmicutes. Both alpha and beta diversity were significantly reduced during fasting. Functional analysis of the gut microbiota suggested a shift toward fatty acid oxidation during fasting. Correlation analysis further demonstrated that the relative abundance of Barnesiella was positively correlated with genes involved in gluconeogenesis and negatively correlated with lipid metabolism genes, such as ELOVL6 and PHGDH. This underscores the role of the gut-liver axis in regulating metabolic adaptations. These findings offer critical insights into how short-term fluctuations in nutrient availability influence immune function, metabolic regulation, and gut microbiota composition in geese. This research also provides potential strategies for optimizing poultry nutrition and health management.
New insights into viral threats in soybean (Glycine max) crops from Bangladesh, including a novel crinivirus
Authors: Khatun Mst. Fatema , Kwak Myeonghwan , Kwon Minhyeok , Hossain Md. Motaher , Kil Eui-Joon
Published: February 2025

Soybean (Glycine max) crops in Bangladesh face significant challenges due to viral diseases, exacerbated by the hot and humid conditions that favor virus and vector proliferation. The emergence of novel or resurgent viruses can jeopardize soybean production because of the difficulties in identifying and characterizing these pathogens. In addition, detecting and characterizing new plant viruses demands considerable resources and commitment. This study examines soybean plants, collected from research fields in Gazipur, Bangladesh, between February 2022 and January 2023, that exhibited green or yellow mosaic, leaf wrinkling, and mild yellowing symptoms. Utilizing high-throughput sequencing, we examined the virome in soybean leaves. Our findings revealed the presence of three RNA viruses—Potyvirus phaseovulgaris (bean common mosaic virus, BCMV), P. phaseoli (bean common mosaic necrosis virus, BCMNV), a novel crinivirus—and one DNA virus, Begomovirus vignaradiataindiaense (mungbean yellow mosaic India virus, MYMIV). This is the first identification of the novel crinivirus, soybean mild yellows Bangladesh virus (SMYBV), in soybean. We assembled four viral genome sequences for phylogenetic analysis. The novel crinivirus is closely related to the criniviruses CCYV, LCV, and PloACV. BCMV and BCMNV exhibited high sequence similarity with a Bangladeshi isolate in the common bean, which indicated the continued spread of BCMV and BCMNV present in Bangladesh. Mixed infections with MYMIV-SMYBV, MYMIV-BCMV-BCMNV, and MYMIV-BCMNV were detected in soybean samples through RT-PCR and PCR.
HSV-1 ICP22 condensates impair host transcription by depleting promoter RNAPII Ser-2P occupation
Authors: Qi Hansong , Yin Mengqiu , Ren Xiaoli , Chen Guijun , Li Ai , Li Yongxia , Cao Xia , Zhou Jumin
Published: February 2025

Herpes simplex virus type I (HSV-1) infection-induced host transcript ion shutdown is one of the most critical hallmarks of viral lytic infection. However, how HSV-1 and which viral factors accomplish this dramatic effect is not well understood. In this study, we show that ICP22-defined condensates shutdown host global transcription but facilitate viral transcription. This is independent of its effects on viral infection-triggered changes in splicing, readthrough, and read-in events. ICP22 condensates depleted the serine-2 phosphorylated RNA polymerase II (RNAPII Ser-2P) occupancy from the host transcription start site (TSS), resulting in decreased host transcripts output. At the same time, it ensures proper RNAPII Ser-2P distribution on the viral genome to promote viral transcription. This effect is dependent solely on the condensate-forming activity, as condensate-disrupting point mutations abolish it. In addition, ectopic expressed ICP22 alone could decrease host transcription activity and increase histone H3K27me3 modification level. Thus, ICP22 condensates shut down host transcription by reducing RNAPII binding to host TSS to impair the host transcription.
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 aims

Elevated 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.

Methods

This 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.

Results

A 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 < 0.003). Other cardiac preconditions or neurological functional parameters did not serve as significant predictors.

Conclusions

Myocardial 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.
Repeated misdiagnosis of squamous cell carcinoma of the thyroid: a case report
Authors: Yu Zheng , Tingting Ding , Jianyong Zhang , Yunsong Peng
Published: February 2025

Squamous cell carcinoma of the thyroid (SCCT) represents a rare subtype of thyroid malignancy characterized by a poor prognosis and is frequently misdiagnosed as subacute thyroiditis (SAT). This report discusses a case of SCCT that was recurrently misdiagnosed with neck pain as the initial clinical presentation. An 80-year-old Asian female presented multiple times to the department of emergency, department of vascular and thyroid surgery, and department of endocrinology due to a painful neck mass. Ultrasonography identified a cystic solid mass in the right thyroid lobe, measuring 4.55 cm*3.2 cm. Enhanced computed tomography (CT) scanning revealed a significant enlargement of the right thyroid lobe, with an irregular mass exhibiting indistinct boundaries and blurred surrounding spaces. Laryngoscopic examination demonstrated immobilization of the right vocal cord and inadequate glottic closure. The erythrocyte sedimentation rate (ESR) was elevated to 94 mm/h. Thyroid function tests indicated subclinical thyrotoxicosis. The patient was initially diagnosed with subacute thyroiditis, and her symptoms improved following treatment with glucocorticoids and analgesics. One month following treatment, the patient experienced dyspnea, and subsequent computed tomography (CT) imaging revealed tracheal compression and narrowing, which contributed to the respiratory distress. A biopsy of the tumor was conducted, and pathological examination confirmed the presence of squamous cell carcinoma. To definitively diagnose SCCT, pathological examination and immunohistochemical analysis are required. Early and accurate diagnosis is essential for developing appropriate treatment strategies and enhancing patient survival rates. It is imperative for clinicians to comprehend this rare and life-threatening disease to enhance treatment efficacy.
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

Introduction

Rare 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.

Methods

We 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.

Results

In 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.

Discussion

Trametinib 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 Registration

clinicaltrials.gov, identifier [NCT06555237].
Understanding intergroup violence justification: the role of ethnicity and perceived threat in Israeli society
Authors: Rozmann Nir
Published: February 2025

Research has shown that perceived realistic and symbolic threats are linked with negative attitudes and prejudice toward out-group members. Additionally, levels of perceived group threat regarding out-groups can affect intergroup violence justification. Based on the Integrated Threat Theory (ITT), the current study aimed to expand existing knowledge by examining a conceptual model in which perceived threat mediates the relationship between ethnicity and intergroup violence justification among Jews and Arabs in Israel. The study involved 324 Israeli-Jewish and 325 Israeli-Arabs, who answered questions regarding perceived out-group threat and intergroup violence justification. Findings revealed that (a) Jews were more likely to justify intergroup violence than Arabs, and (b) perceived realistic threat mediates the relationship between ethnic affiliation and intergroup violence justification only among Jews. These results underscore the importance of understanding intergroup conflicts in the field of criminology.
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

Background

Prenatal 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.

Methods

A 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.

Results

A 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.

Conclusion

Maternal 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.
Longitudinal association between handgrip strength and depressive symptoms in middle-aged and older Chinese adults: mediating role of functional limitation
Authors: Liu Yanchang , Cui Junling , Luo Xin , Wang Zhuzhu , Shen Ziyi , Fang Yan , Li Chengcheng , Hong Jingfang
Published: February 2025

Background

The relationship between handgrip strength (HGS) at baseline and subsequent depressive symptoms among middle-aged and older Chinese adults remains highly uncertain. This research endeavored to investigate the effect of functional limitation on the association between these two variables.

Methods

A total of 5,684 participants aged ≥45 years from the China Longitudinal Study of Health and Retirement (CHARLS) were enrolled, using data from the 2015 and 2018 waves. Functional limitation was evaluated based on participants’ self-reported basic activities of daily living (BADL) and instrumental activities of daily living (IADL). Logistic regression models were utilized to analyze the relationship between HGS and subsequent depressive symptoms, and bootstrap analysis was performed to explore the potential mediating role of functional limitation.

Results

After adjusting for confounders, an inverse correlation was detected between HGS and functional limitation (B = -0.885, p < 0.001), a positive correlation was found between functional limitation and subsequent depressive symptoms (B = 1.054, p < 0.001). The mediated effect size of HGS on depressive symptoms through functional limitation was a*b = −0.933 (BCa 95% CI: −1.224, −0.642). Functional limitation had a significant impact on 18.9% of the overall association.

Conclusion

Among the Chinese middle-aged and senior population, functional limitation accounted for 18.9% of the connection between HGS and depressive symptoms. Interventions targeting the enhancement of muscle strength should be regarded as crucial elements for maintaining physical function and preventing depressive symptoms.
Comparison of myopia-related behaviors among Chinese school-aged children and associations with parental awareness of myopia control: a population-based, cross-sectional study
Authors: Ye Chaoying , Wang Yujie , Liu Yujia , Zhu Xingxue , Shang Jianmin , Qu Xiaomei
Published: February 2025

Background

In China, approximately 30 and 70% of primary and middle school students, respectively, have myopia, making myopia prevention and control necessary. Eye-use behaviors are closely related to myopia, highlighting the importance of determining the behavioral compliance rates of children. Parental awareness also affects children’s behaviors. Therefore, we assessed the myopia-related behaviors and parental awareness of school-aged children in different city tiers of China with different refractive statuses.

Methods

A population-based, cross-sectional study was conducted on Chinese children from 110 cities aged 7–15 years. Samples were equally allocated to each subgroup of city tiers, children’s age groups, and children’s refractive statuses. Questionnaires were designed to investigate children’s behaviors, including responses to sitting position, time of eye use (single continuous near work time and breaks in between, total near work time after school each day), eye rest (break time and style during near work and outdoor time per week), light conditions in the learning environment at home, and parents’ knowledge about myopia prevention and control. Associations between parental awareness and children’s behaviors were analyzed using logistic regression.

Results

In total, 896 questionnaires were collected. The prevalence of children’s poor behaviors related to myopia ranged from 23.44 to 84.82%, with the highest and lowest being sitting position and the use of eye-protecting lamps, respectively. Children in third-tier cities were more likely to have poor sitting position (p < 0.01), a non-open view in front of a desk at home (p = 0.02), and more near activities during break times (p = 0.04). After adjustment for parental myopia condition and the child’s sex, poor parental awareness was mainly associated with not using an eye-protecting lamp (odds ratio [OR]: 1.95, 95% confidence interval [CI]: 1.40–2.72), poor break styles (OR: 1.60, 95% CI: 1.21–2.12), and excessive total near work time (OR: 1.45, 95% CI: 1.02–2.05).

Conclusion

Myopia-related behaviors were poorly performed in children, particularly among older children and those living in third-tier cities. Eye-protecting lamps, time spent doing near work, and break style were all associated with parental awareness, suggesting that better parental awareness helps children in the long run. More targeted measures could be adopted to help improve children’s behaviors.
Health literacy and chronic disease: a comparison of somatic and mental illness
Authors: Griese Lennert , Schaeffer Doris
Published: February 2025

Background

Health literacy (HL) is increasingly recognized as essential for preventing and managing chronic illness but also for strengthening health resources and skills. However, studies on HL of people with chronic illness that adopt a multidimensional approach encompassing the three HL domains health care, disease prevention, and health promotion, remain scarce. This study aims to (a) compare HL across these three domains in individuals with chronic somatic illness, chronic mental illness and those without any chronic illness, (b) to explore where difficulties in managing health-related information occur and how these differ between groups, and (c) to analyze the relationship between demographic, social, and psychological factors and HL.

Methods

Data from a quantitative cross-sectional survey in Germany were stratified according to respondents with at least one chronic somatic illness, at least one chronic mental illness and without chronic illness. The survey was conducted by means of paper-assisted personal interviews. HL was measured in three domains health care, disease prevention and health promotion. Age, educational level, social status, financial resources, number of chronic illnesses, social support, and self-efficacy were included in the analysis as potential determinants of HL. Differences between groups were analyzed using bivariate statistics; multiple linear regressions were calculated to examine relationships between potential determinants and HL.

Results

Respondents with chronic mental illness showed lowest HL, followed by those with chronic somatic illness. Respondents without chronic illness achieved highest HL. This pattern was consistent across all three HL domains. Among all groups, HL was lowest in the domain of health promotion. Notable differences emerged in perceived difficulties, with respondents with mental illnesses reporting the most significant challenges. Self-efficacy and education level showed a positive association with HL across all groups, while social support was positively associated with HL among individuals with chronic mental illness. For respondents with chronic somatic illness, age was negatively associated with HL, whereas social status showed a positive association. Female respondents without chronic illness and those with chronic somatic illness demonstrated higher HL compared to male respondents.

Conclusion

This study advances the understanding of HL among individuals with chronic illness and highlights the need for a greater differentiation among disease groups and HL domains in future research. Particular attention should be paid to people with chronic mental illness, whose lower HL levels increase their vulnerability.