bluuebunny/crossref_metadata_2025 huggingface dataset:
Pre- and post-pandemic comparisons in cardiovascular markers: a population-based study
Authors: Nehme Mayssam , Zaballa Maria Eugenia , Rouzinov Serguei , Lamour Julien , Stringhini Silvia , Guessous Idris
Published: January 2025

Introduction

The COVID-19 pandemic, starting in 2020, raised concerns about potential long-term health impacts, including its effects on cardiovascular health and related biomarkers. This study part of the Bus Santé in Geneva, Switzerland, compared cardiovascular and metabolic profiles pre- (2016–2019) and post-pandemic (2023–2024) among individuals aged 30–75.

Methods

Participants completed questionnaires and underwent a clinical visit, including a physical examination and fasting blood test to assess lipid and glycemic profiles. Linear regression was used to estimate results including mean systolic and diastolic blood pressure, cholesterol, and glycemic profiles, after adjusting for age, sex, smoking, and socioeconomic status. Quantile regression models were used to estimate median values.

Results

A total of 4,558 participants were included. The study observed modest declines in mean glucose, cholesterol, HDL, and LDL levels post-pandemic, with stable blood pressure. The prevalence and treatment rates of diabetes, hypertension, and dyslipidemia remained consistent. Unawareness of these conditions was stable.

Conclusion

Despite initial fears of a pandemic-induced health debt, results indicate healthy cardiovascular profiles post-pandemic, likely driven by improved lifestyle behaviors. This study highlights the importance of monitoring of cardiovascular health and suggests that lifestyle improvements may offset potential adverse pandemic effects in developed nations like Switzerland.
Establishment and validation of a nomogram for coronary artery lesions in children with Kawasaki disease
Authors: Hu Chong , Yan Xiao , Song Henglian , Dong Qin , Yi Changying , Li Jianzhi , Lv Xin
Published: January 2025

Background

The nomogram is a powerful and robust tool in disease risk prediction that summarizes complex variables into a visual model that is interpretable with a quantified risk probability. In the current study, a nomogram was developed to predict the occurrence of coronary artery lesions (CALs) among patients with Kawasaki disease (KD). This is especially valuable in the early identification of the risk of CALs, which will lead to proper diagnosis and treatment to reduce their associated complications.

Methods

Retrospective clinical data of 677 children diagnosed with KD who were treated in the Children's Hospital Affiliated with Shandong University were analyzed. All the participants were divided into the CAL group and no CAL group according to their coronary echocardiography results. Least absolute shrinkage and selection operator (LASSO) regression was applied for the identification of the most informative predictors of CAL. Based on this, a nomogram was developed for accurate risk estimation.

Results

The data were divided into a training set and a validation set. Receiver operating characteristic analysis, calibration curves, and decision curve analysis all supported the high accuracy and clinical utility of this model. LASSO regression highlighted five key predictors: sodium, hemoglobin, platelet count, D-dimer, and cystatin C. A nomogram based on these predictors was established and successfully validated in both datasets. In the training set, the AUC was 0.819 and in the validation set it was 0.844. The C-index of the calibration curve in the training set was 0.820, while in the validation set it was 0.844. In the decision curve analysis, the predictive benefit of the model was greater than zero when the threshold probability was below 95% in the training set and below 92% in the validation set.

Conclusion

The predictive factors identified through the LASSO regression approach and the development of the nomogram are important contributions in this respect. This model had a high predictive accuracy and reliability for identifying high-risk children in the very early stage of disease with remarkable precision, laying the foundation for personalized treatment strategies and targeted treatment and providing a strong scientific basis for precise therapeutic intervention.
Harnessing hardware acceleration in high-energy physics through high-level synthesis techniques
Authors: Leguina Pelayo , Folgueras Santiago
Published: January 2025

At the Large Hadron Collider, the vast amount of data from experiments demands not only sophisticated algorithms but also substantial computational power for efficient processing. This paper introduces hardware acceleration as an essential advancement for high-energy physics data analysis, focusing specifically on the application of High-Level Synthesis (HLS) to bridge the gap between complex software algorithms and their hardware implementation. We will explore how HLS facilitates the direct implementation of software algorithms into hardware platforms such as FPGAs, enhancing processing speeds and enabling real-time data analysis. This will be highlighted through the case study of a track-finding algorithm for muon reconstruction with the CMS experiment, demonstrating HLS’s role in translating computational tasks into high-speed, low-latency hardware solutions for particle detection and reconstruction. Key techniques in HLS, including parallel processing, pipelining, and memory optimization, will be discussed, illustrating how they contribute to the efficient acceleration of algorithms in high-energy physics. We will also cover design methodologies and iterative processes in HLS to optimize performance and resource utilization, alongside a brief mention of additional techniques like algorithm approximation and hardware/software co-design. In short, this paper will underscore the potential of hardware acceleration in high-energy physics research, emphasizing HLS as a powerful tool for physicists to enhance computational efficiency and foster groundbreaking discoveries.
An updated look at the use of silver diamine fluoride in U.S. dental schools' predoctoral curriculum—a survey
Authors: Jakubauskas Benas , Pagni Sarah , Ferreira Zandona Andrea G.
Published: January 2025

This survey aimed to update Silver Diamine Fluoride (SDF) use/teaching in U.S. predoctoral dental education programs in comparison to a 2016 survey, considering the COVID-19 pandemic. An online survey via email was sent to all accredited U.S. predoctoral dental education programs (n = 68) in January 2022. A total of 39 schools (57% response rate) responded to the survey, and all 39 of them reported that SDF was now part of their curriculum, significantly different (p < 0.001) from 2016 (68% of schools). Significant changes (p < 0.001) were reported in the survey responses from 2016 to 2022, particularly in how SDF was being taught (97% teaching didactically and clinically vs. 48% in 2016), but were not necessarily a response to the COVID pandemic. Schools report teaching more indications for the use of SDF and using more specific protocols with more schools teaching arresting caries in permanent teeth (97% vs. 78% in 2016). Since 2016, the use and teaching of SDF have been increasingly adopted across U.S. dental schools, though there remains room for improvement in terms of consistent implementation, specific clinical protocols, and comprehensive training.
Evolution characteristics and invulnerability simulation analysis of global zirconium ore trade network
Authors: Luo Fanjie , Liu Wei , Xu Mao , Liu Qunyi , Wang Junbo
Published: January 2025

The burgeoning demand for zirconium, driven by the rapid development of smart devices, low-carbon energy technologies, and other emerging industries, underscores the importance of understanding the dynamics of its global trade network. However, the evolutionary patterns of the international zircon ore trade network and its resilience to disruptions remain unclear. This study constructs the international zircon ore trade network from 2013 to 2022, analyzes its structural evolution at both the network and node levels, and evaluates its robustness in 2022 using five attack strategies: random node removal, random edge removal, edge degradation, targeted removal based on node degree, and targeted removal based on node betweenness centrality. Our findings reveal that: (1) the international zircon ore trade network exhibits a shift in the import market towards Asia, with the export market dominated by Spain, the United States, and Brazil. China plays a crucial role as a bridge connecting various countries, while Japan exerts significant influence within the network; (2) the network is particularly vulnerable to targeted attacks based on node degree and betweenness centrality, highlighting the potential for significant disruption following the removal of key nodes. This study provides valuable insights for ensuring the stable and sustainable supply and consumption of zirconium resources, informing the development of targeted policies for countries and relevant industries.
Flash flood simulation based on distributed hydrological model in future scenarios
Authors: Liu Qi , Zhang Nan , Wang Lingling , Yu Kunxia , Wu Jiayi , Wang Jingqi , Ma Meihong
Published: January 2025

Extreme rainfall events are frequent, particularly in economically underdeveloped hilly areas, where conventional hydrological models struggle to accurately simulate the formation of flash floods. Therefore, this study focuses on the Daxi River Basin in Guangdong Province. First, CMIP6 precipitation data is utilized to analyze the future precipitation variations on interannual and monthly scales. Compared to the baseline period, the annual precipitation increases under all three scenarios. Next, design storms with a return period greater than 2 years are allocated into rainfall patterns. By combining the accumulated precipitation with the soil moisture content, different distributed hydrological models are applied to calculate the corresponding flood discharges for different rainfall events. The results indicate that: 1) Precipitation under the SSP5-8.5 scenario is generally higher than under the SSP1-2.6 and SSP2-4.5 scenarios, with the SSP1-2.6 scenario showing the mildest increase. 2) The peak flood simulated by the CREST model are relatively low, at 235.4 m³/s, with fewer precipitation events covered, which is significantly lower than the simulation accuracy of the CNFF model. 3) The Daxi River Basin has a low probability of experiencing flash flood disasters exceeding the 10-year return period in the period from 2026 to 2070. The above research results will provide important references for flash flood disaster prevention in similar basins.
ChatGPT as a data analyst: an exploratory study on AI-supported quantitative data analysis in empirical research
Authors: Prandner Dimitri , Wetzelhütter Daniela , Hese Sönke
Published: January 2025

Social scientists are faced with the challenge of designing complex studies and analyzing collected data via various programs such as R, Stata, SPSS, or Python. This often requires the use of analytical procedures and specific software packages that are beyond an individual’s established skillsets and technical knowledge. To address these challenges, generative artificial intelligence, such as ChatGPT, can now be employed as ‘assistants’—with both associated risks and benefits. Accordingly, this paper explores the potential and pitfalls of using a tool like ChatGPT as an assistant in quantitative data analysis. We investigate the practical use of ChatGPT-3.5 by replicating analyses and findings in everyday scientific research. Unlike previous studies, which have primarily focused optimizing the use of chatbots for code generation, our approach examines an amateur level use of AI tools to support and reference regular research activities, with an emphasis on minimal technical expertise. While we overall conducted three experiments, with the goal to replicate academic papers, the article’s focus is on the methodologically most complex one, by De Wet et al. from 2020. In this case AI is used for the step-by-step replication of the two-dimensional model of value types proposed by Schwartz (2012). The results of this experiment highlight the challenges of using ChatGPT 3.5 for specific, detailed tasks in academic research, as a tendency for responses to repeat in loops when solutions were not readily available emerged at several stages. Thus, we concluded that there are severe limitations in the AI’s ability to provide accurate and comprehensive solutions for complex tasks and emphasize the need for caution and verification when using AI powered tools for complex research procedures.
Lessons learned from the expansion of medical schools in Brazil: a review of challenges and opportunities
Authors: Avena Katia M. , Quintanilha Luiz F. , Luzardo Filho Ricardo Luiz , Andrade Bruno B.
Published: January 2025

Brazil faces significant challenges in the equitable distribution of health professionals across its vast territory, with remote and underdeveloped areas often lacking doctors. Initiatives like “Programa Mais Médicos” have expanded medical courses and residency programs nationwide. Recently, new Ministry of Education guidelines authorized courses and increased slots in response to judicial demands, highlighting the complexity of Brazil’s educational and health landscape. This initiative increased available slots, particularly in areas lacking healthcare professionals, and attracted private institutions to the medical sector. Despite advancements in expansion and geographical distribution, there are criticisms and challenges facing the current medical training process. Against this backdrop, this study offers a critical analysis of Brazil’s medical education, drawing from the experience of experts involved in the implementation of new medical schools in the Brazilian Northeast and Midwest regions. The study outlines the history, challenges, and outcomes of government policies, reflecting on future impacts and contributing to the debate on medical training quality and health service provision amidst the expansion and privatization of medical education in the country. We hope the lessons and insights can guide Brazil and other countries facing similar challenges, inspiring innovative and sustainable solutions to complex issues of doctor shortage and unequal distribution.
CARP VIII antibody-related autoimmune cerebellar ataxia in a child after Mycoplasma pneumoniae infection: a case report
Authors: Li Minglei , Han Zongming , Li Jinlei , Wang Qianyun , Lv Zufang
Published: January 2025

Autoimmune cerebellar ataxia (ACA) is a cerebellar syndrome induced by autoimmune reactions and its onset is induced by malignant tumors, prodromic infection, and gluten allergy. Its clinical symptoms include gait disorder, limb ataxia, dysarthria, and dysphagia. According to the Chinese Expert Consensus on the Diagnosis and Management of Autoimmune Encephalitis 2024, the diagnosis of ACA is based on the following points: 1. subacute or acute onset of the disease, with cerebellar syndrome as the main manifestation; 2. The cranial magnetic resonance imaging (MRI) in the early stage of the disease (within three months) does not show significant atrophy of the cerebellum and brainstem; 3. presence of either of the following: 1) positive anti-cerebellar antibodies in serum and/or cerebrospinal fluid cell-based assay (CBA), 2) at least two of the following are present: ① the patient or first-degree relative has a history of autoimmune disease, ② cerebrospinal fluid leukocytes >5×106/L, or positive for cerebrospinal fluid specific oligoclonal bands, ③ tissue-based assay (TBA) revealing the characteristic fluorescent form of Purkinje cell antibody, and ④ the presence of systemic autoimmune disease-related antibodies; and 4. the absence of other diseases. Currently, fewer instances of ACA have been associated with positive results for carbonic anhydrase-related protein VIII (CARP VIII). Three case reports have been detected by this antibody in adults with ovarian cancer, breast cancer, or melanoma, and there is no report on this antibody in children. Moreover, neurological diseases associated with mycoplasma pneumoniae infection are increasingly being reported. Therefore, the correlation between this infection and autoimmune encephalitis antibodies needs to be further investigated.
Serum lipid profile in systemic lupus erythematosus
Authors: Xuan Jingxiu , Deng Chaoqiong , Lu Huiqin , He Yan , Zhang Jimin , Zeng Xiaoli , Sun Yuechi , Chen Shiju , Liu Yuan
Published: January 2025

Background

Dyslipidemia presents in various autoimmune diseases, and the serum lipid profile in systemic lupus erythematosus (SLE) has not yet been clearly defined. This study aims to evaluate the level of serum lipids in patients with SLE.

Methods

A case–control study evaluated four conventional sera lipids—total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL)—in patients with SLE compared to healthy controls (HCs). Correlations between serum lipids and clinical characteristics were analyzed in patients with SLE. A systematic review and meta-analysis were conducted to assess the epidemiology of lipid profiles in patients with SLE, and a random-effects meta-analysis was performed for data synthesis.

Results

TC and TG were elevated significantly, and HDL decreased in patients with SLE compared to HCs. Elevated lipids were associated with progressive disease activity. TC, TG, and HDL were elevated in patients with SLE and were associated with decreased IgG, increased 24-h proteinuria, white blood cells (WBCs), and neutrophils. Decreased HDL and increased TG were associated with an increase in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Patients with SLE who took glucocorticoids (GCs) may have experienced increases in TC and TG, while those who took hydroxychloroquine (HCQ) may have experienced increases in TC and HDL. Eleven eligible studies including the present study on associations between serum lipids and SLE were reviewed by the meta-analysis. The results demonstrated elevated TC (MD = 0.85, 95% CI 0.82 to 0.89, p < 0.00001) and TG (MD = 0.96, 95% CI 0.94 to 0.99, p < 0.00001) levels in SLE, while HDL decreased (MD = −0.19, 95% CI −0.20 to −0.17, p < 0.00001).

Conclusions

Dyslipidemia is present in SLE. There was a significant association between SLE disease activity and TC, TG, and HDL. The exact pathogenesis of metabolic disorders in SLE needs to be further addressed.
Mixed radiation with different doses induces CCL17 to recruit CD8+T cell to exert anti-tumor effects in non-small cell lung cancer
Authors: Huang Liuying , Wang Duo , Xu Muchen , Qian Danqi , Cao Yulin , Wu Xiaohan , Ming Liang , Tang Junhui , Huang Zhaohui , Yin Yuan , Zhou Leyuan
Published: January 2025

Background

Different doses of radiotherapy (RT) exert diverse effects on tumor immunity, although the precise irradiation method remains unknown. This study sought to elucidate the influence of combining different doses of RT with immune checkpoint inhibitors (ICIs) on the infiltration of CD8+T cells within tumors, thereby augmenting the anti-tumor response.

Methods

Constructing a mouse model featuring bilateral lung cancer tumors subjected to high and low dose irradiation, the analysis of RNA transcriptome sequencing data and immunohistochemical validation for tumors exposed to various dosages guided the selection of the optimal low-dose irradiation scheme. Subsequently, upon the integration of immune checkpoint inhibitors (ICIs) therapy, the infiltration of immune cells within the tumor was ascertained via immunohistochemistry (IHC) and flow cytometry (FCM). Finally, through bioinformatics analysis and experimental verification, potential strategies to bolster the anti-tumor immune response were investigated.

Results

In comparison to the administration of 20Gy alone to the primary tumor, supplementing with 6Gy directed at the abscopal tumor produces a more pronounced abscopal response. The synergy of 20Gy, 6Gy, and ICIs markedly boosts the efficiency of ICIs. According to the findings from IHC and FCM studies, the triple therapy group exhibits a heightened infiltration of immune cells into the tumor, largely attributable to the augmented expression of CCL17 within the tumor under these irradiation regimens, which subsequently draws CD8+ T cells to infiltrate the tumor site, exerting cytotoxic effects.

Conclusion

Our study shows that the combined application of 20Gy and 6Gy can enhance the infiltration of tumor CD8+T cells in mice and improve the effectiveness of immunotherapy.
Epigenetic profiling for prognostic stratification and personalized therapy in breast cancer
Authors: Guo Xiao , Feng Chuanbo , Xing Jiaying , Cao Yuyan , Liu Tengda , Yang Wenchuang , Mu Runhong , Wang Tao
Published: January 2025

Background

The rising incidence of breast cancer and its heterogeneity necessitate precise tools for predicting patient prognosis and tailoring personalized treatments. Epigenetic changes play a critical role in breast cancer progression and therapy responses, providing a foundation for prognostic model development.

Methods

We developed the Machine Learning-derived Epigenetic Model (MLEM) to identify prognostic epigenetic gene patterns in breast cancer. Using multi-cohort transcriptomic datasets, MLEM was constructed with rigorous machine learning techniques and validated across independent datasets. The model’s performance was further corroborated through immunohistochemical validation on clinical samples.

Results

MLEM effectively stratified breast cancer patients into high- and low-risk groups. Low-MLEM patients exhibited improved prognosis, characterized by enhanced immune cell infiltration and higher responsiveness to immunotherapy. High-MLEM patients showed poorer prognosis but were more responsive to chemotherapy, with vincristine identified as a promising therapeutic option. The model demonstrated robust performance across independent validation datasets.

Conclusion

MLEM is a powerful prognostic tool for predicting breast cancer outcomes and tailoring personalized treatments. By integrating epigenetic insights with machine learning, this model has the potential to improve clinical decision-making and optimize therapeutic strategies for breast cancer patients.
Targeting glycolysis: exploring a new frontier in glioblastoma therapy
Authors: Yang Lu , Li Sijia , Yu Lei , Leng Jiao , Li Na
Published: January 2025

Glioblastoma(GBM) is a highly malignant primary central nervous system tumor that poses a significant threat to patient survival due to its treatment resistance and rapid recurrence.Current treatment options, including maximal safe surgical resection, radiotherapy, and temozolomide (TMZ) chemotherapy, have limited efficacy.In recent years, the role of glycolytic metabolic reprogramming in GBM has garnered increasing attention. This review delves into the pivotal role of glycolytic metabolic reprogramming in GBM, with a particular focus on the multifaceted roles of lactate, a key metabolic product, within the tumor microenvironment (TME). Lactate has been implicated in promoting tumor cell proliferation, invasion, and immune evasion. Additionally, this review systematically analyzes potential therapeutic strategies targeting key molecules within the glycolytic pathway, such as Glucose Transporters (GLUTs), Monocarboxylate Transporters(MCTs), Hexokinase 2 (HK2), 6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase 3 (PFKFB3), Pyruvate Kinase Isozyme Type M2 (PKM2), and the Lactate Dehydrogenase A (LDHA). These studies provide a novel perspective for GBM treatment. Despite progress made in existing research, challenges remain, including drug penetration across the blood-brain barrier, side effects, and resistance. Future research will aim to address these challenges by improving drug delivery, minimizing side effects, and exploring combination therapies with radiotherapy, chemotherapy, and immunotherapy to develop more precise and effective personalized treatment strategies for GBM.
Neutralizing antibody landscape of the non-polio Enteroviruses and future strategy
Authors: Wang Hongye , Zhu Wenbing , Li Ya , Sun Ming
Published: January 2025

The non-polio Enteroviruses (NPEVs), consist of enteroviruses, coxsackieviruses, echoviruses, and rhinoviruses, are causative agents for a wide variety of diseases, ranging from common cold to encephalitis and acute flaccid paralysis (AFP). In recent years, several NPEVs have become serious public health threats, include EV-A71, which has caused epidemics of hand-foot-and-mouth disease (HMFD) in Southeast Asia, and EV-D68, which caused outbreaks of severe respiratory disease in children worldwide. Infections with these viruses are associated with neurological diseases like aseptic meningitis and AFP. Currently, apart from inactivated EV-A71 vaccines that were developed in China, no effective measures are available to prevent or treat NPEV infections. Antibody-mediated immunity is crucial for preventing and limiting viral infections, and potent neutralizing antibodies could serve as potential therapeutic agents. In this review, we describe recent progress in the NPEVs neutralization antibodies, summarizing the characteristics, breadth, and potency against NPEVs, such as EV-A71, CVA16, EV-D68, and echovirus. We focus on not only through the study of viral epitopes but also through the understanding of virus-antibody interactions. Also, we decipher the role of antibodies in the attachment of the virus to receptors, internalization, and uncoating process, providing insight into virus neutralization mechanisms. Moreover, bi-specific antibodies or multivalent antibodies with better potency are also discussed. Therefore, an in-depth understanding of structures of enterovirus and mechanisms of antibody neutralization should be useful for future strategies in guiding the design of a rational antiviral agent against NPEVs infections.
Iron improves the antiviral activity of NK cells
Authors: Schimmer Simone , Sridhar Vaasudevan , Satan Zelal , Grebe Anton , Saad Mohamed , Wagner Bernd , Kahlert Nele , Werner Tanja , Richter Dana , Dittmer Ulf , Sutter Kathrin , Littwitz-Salomon Elisabeth
Published: January 2025

Natural killer (NK) cells are innate immune cells that play a crucial role as a first line of defense against viral infections and tumor development. Iron is an essential nutrient for immune cells, but it can also pose biochemical risks such as the production of reactive oxygen species. The importance of iron for the NK cell function has gained increasing recognition. We have previously shown that NK cells require iron to efficiently eliminate virus-infected target cells; however, the impact of nutritional iron deficiency on NK cell function and the therapeutic benefits of iron supplementation remain unclear. Here, we demonstrate that diet-related low iron levels lead to increased retroviral loads due to functional NK cell impairment, while iron supplementation enhances NK cell proliferation, as well as their cytotoxic efficacy. Notably, iron-treated NK cells exhibited significant metabolic changes, including mitochondrial reorganization. Interestingly, although iron supplementation decreased the NK cell’s cytokine production, it significantly improved NK cell degranulation and the expression of cytotoxicity-associated proteins. These findings highlight the critical role of iron in maintaining NK cell immunity and suggest that iron supplementation may hold therapeutic potential for supporting the treatment of viral infections and immunodeficiency disorders.
A c-type lectin HcLec1 with dual function of immunology and mineralization from the freshwater oyster (Hyriopsis cumingii Lea)
Authors: Chen Xiaofeng , Shen Xiaoya , Liu Shijun , Li Wenjuan , Wang He , Li Jiale , Bai Zhiyi
Published: January 2025

Background

Shell and pearl formation in bivalves is a sophisticated biomineralization process that encompasses immunological and mineralization aspects, particularly during shell repair and the initial stages of pearl cultivation when a nucleus is inserted. Here, we describe a novel C-type lectin, HcLec1, isolated and characterized from the freshwater pearl mussel Hyriopsis cumingii Lea.

Methods

Immune challenge, RNA interference (RNAi) experiments, ELISA, and antibacterial assays were employed to investigate the role of HcLec1 in innate immunity. We also established shell damage repair and pearl nucleus insertion models to examine the impact of HcLec1 on the biomineralization process in Hyriopsis cumingii Lea. In vitro calcium carbonate crystallization assays were conducted to explore the direct role of HcLec1 in calcium carbonate crystal formation.

Results

The HcLec1 gene sequence is a full-length cDNA of 1552 bp, encoding 240 amino acids. HcLec1 comprises an N-terminal signal peptide and a carbohydrate-recognition domain (CRD), with QPD (Gln-Pro-Asp) and MND (Met-Asn-Asp) motifs for polysaccharide binding. Tissue expression analysis showed that HcLec1 is predominantly expressed in the gill tissue of Hyriopsis cumingii Lea under normal conditions, and its expression is significantly elevated in both gill and pearl sac tissues following nucleus insertion for pearl cultivation (P < 0.05). After immune stimulation with Aeromonas hydrophila and lipopolysaccharides (LPS), HcLec1 expression levels significantly increased in both cases (P < 0.01), indicating a role in bivalve innate immunity. RNA interference (RNAi)-mediated knockdown of HcLec1 led to a significant decrease in the expression levels of immune-related genes (WAP, α2m, and Lyso) and mineralization-related genes (CA, CHS, Nacrein, and Pif) (P < 0.05). In animal models for shell damage and nucleus insertion in pearl cultivation, HcLec1 showed a consistent expression pattern, with an initial significant decrease followed by a marked increase, peaking at day 14 (P < 0.05). This suggests a role for HcLec1 in pearl formation and shell repair. The recombinant HcLec1 protein demonstrated binding affinity to LPS and PGN, a robust ability to agglutinate Escherichia coli, Staphylococcus aureus, Aeromonas veronii, and Aeromonas hydrophila, and significantly inhibited bacterial growth (P < 0.05). Moreover, rHcLec1 promoted calcite crystal formation in saturated calcium carbonate solutions and altered crystal morphology.

Discussion

The HcLec1 gene plays a pivotal role in both innate immunity and biomineralization in the triangle sail mussel. This study enhances our understanding of the functional diversity of C-type lectins and provides a foundation for future studies on shell repair and pearl growth.
Immunometabolic alterations in type 2 diabetes mellitus revealed by single-cell RNA sequencing: insights into subtypes and therapeutic targets
Authors: Li Huahua , Zou Lingling , Long Zhaowei , Zhan Junkun
Published: January 2025

Background

Type 2 Diabetes Mellitus (T2DM) represents a major global health challenge, marked by chronic hyperglycemia, insulin resistance, and immune system dysfunction. Immune cells, including T cells and monocytes, play a pivotal role in driving systemic inflammation in T2DM; however, the underlying single-cell mechanisms remain inadequately defined.

Methods

Single-cell RNA sequencing of peripheral blood mononuclear cells (PBMCs) from 37 patients with T2DM and 11 healthy controls (HC) was conducted. Immune cell types were identified through clustering analysis, followed by differential expression and pathway analysis. Metabolic heterogeneity within T cell subpopulations was evaluated using Gene Set Variation Analysis (GSVA). Machine learning models were constructed to classify T2DM subtypes based on metabolic signatures, and T-cell-monocyte interactions were explored to assess immune crosstalk. Transcription factor (TF) activity was analyzed, and drug enrichment analysis was performed to identify potential therapeutic targets.

Results

In patients with T2DM, a marked increase in monocytes and a decrease in CD4+ T cells were observed, indicating immune dysregulation. Significant metabolic diversity within T cell subpopulations led to the classification of patients with T2DM into three distinct subtypes (A-C), with HC grouped as D. Enhanced intercellular communication, particularly through the MHC-I pathway, was evident in T2DM subtypes. Machine learning models effectively classified T2DM subtypes based on metabolic signatures, achieving an AUC > 0.84. Analysis of TF activity identified pivotal regulators, including NF-kB, STAT3, and FOXO1, associated with immune and metabolic disturbances in T2DM. Drug enrichment analysis highlighted potential therapeutic agents targeting these TFs and related pathways, including Suloctidil, Chlorpropamide, and other compounds modulating inflammatory and metabolic pathways.

Conclusion

This study underscores significant immunometabolic dysfunction in T2DM, characterized by alterations in immune cell composition, metabolic pathways, and intercellular communication. The identification of critical TFs and the development of drug enrichment profiles highlight the potential for personalized therapeutic strategies, emphasizing the need for integrated immunological and metabolic approaches in T2DM management.
Curvilinear association between Framingham Steatosis Index and chronic kidney disease: a nationwide cross-sectional study
Authors: Jiang Chunqi , Wang Bo , Wang Jun , Qu Yinuo , Zhang Xin
Published: January 2025

Introduction

Fatty liver disease is potentially linked to chronic kidney disease (CKD), yet the association between the Framingham Steatosis Index (FSI) and CKD remains uncharted. Our study thoroughly investigated the correlation between FSI and CKD, aiming to elucidate the underlying links between these two conditions.

Methods

The relationship between FSI and CKD was evaluated using a weighted multivariate logistic regression model, and the curvilinear relationship between FSI and CKD was explored through smooth curve fitting. We engaged a recursive partitioning algorithm in conjunction with a two-stage linear regression model to determine the inflection point. By conducting stratified analyses, the heterogeneity within subpopulations was explored.

Results

In the fully adjusted Model 3, which accounted for all covariates, the odds ratios (ORs) (95% CI) for the association between FSI and CKD were 1.01 (0.97, 1.06), indicating no significant statistical association. Sensitivity analysis confirms the stability of the relationship between FSI and CKD. Smooth curve fitting discloses a non-linear association between FSI and CKD. The two-piecewise linear regression model, applied to explore this non-linearity, identified an inflection point at an FSI value of −3.21. Below this threshold, the OR (95% CI) was 0.25 (0.17, 0.37), signifying an inverse correlation between FSI and CKD. Above the inflection point, the OR (95% CI) was 1.19 (1.13, 1.25), suggesting a positive correlation. In the stratified curve analysis, the results were essentially consistent with the overall findings, except for the subgroups with BMI > 30 and age > 50.

Conclusion

We found a curvilinear relationship between FSI and CKD.
Ocular inoculation of toad venom: toxic cataract and proteomic profiling
Authors: Lyu Danni , Ni Shuang , Xu Jia , Zhu Sha , Xu Jing-Wei , Feng Yixuan , Shi Ce , Xu Wen
Published: January 2025

Purpose

To report a singular case of cataract caused by toad venom inoculation and to scrutinize the pathological mechanisms through proteomic sequencing of the lens specimen.

Methods

A young Chinese male presented with progressively deteriorating vision in his right eye subsequent to a history of toad venom inoculation. He was diagnosed with a toxic cataract, and underwent phacoemulsification cataract surgery. Anterior capsule, nucleus, and cortex specimens from the patient (designated as PT_CAP, PT_PHACO, and PT_CTX, respectively) and age-related cataract controls (C_CAP, C_PHACO, and C_CTX, respectively) were collected and subjected to 4D label-free quantitative proteomics.

Results

A multitude of differentially expressed proteins (DEPs) were identified in the patient’s lens compared to those in the controls. Specifically, a total of 204 DEPs were identified in PT_CAP compared to C_CAP, with MYH6, MYL2, MYL3, STAT1, and ANK1 among the foremost regulated DEPs. The DEPs of PT_CAP were principally affiliated with functions including “transportation of small molecules,” “regulation of metal ion transport,” and “import into cell.” A sum of 109 DEPs were delineated in PT_CTX compared to C_CTX, with TPM1 among the top-10 downregulated DEPs. Ninety-five DEPs were pinpointed in PT_PHACO compared to C_PHACO, with hexokinase among the top 10 downregulated DEPs. These proteins were ascertained to be linked with Na+/K+-ATPase activity.

Conclusion

This study introduced the first documented case of toxic cataract caused by toad venom inoculation. Proteomic sequencing indicated a correlation between cataract and alterations in Na+/K+-ATPase activity, providing insights for the clinical management of ocular toad venom inoculation in subsequent cases.
Water pollution, cholera, and the role of probiotics: a comprehensive review in relation to public health in Bangladesh
Authors: Chowdhury Md. Rayhan , Islam Ariful , Yurina Valentina , Shimosato Takeshi
Published: January 2025

Cholera, a disease caused by Vibrio cholerae, remains a pervasive public health threat, particularly in regions with inadequate water sanitation and hygiene infrastructure, such as Bangladesh. This review explores the complex interplay between water pollution and cholera transmission in Bangladesh, highlighting how contaminated water bodies serve as reservoirs for V. cholerae. A key focus is the potential role of probiotics as a novel intervention approach for cholera prevention and management. Probiotics are promising as an adjunctive approach to existing therapies as they can enhance gut barrier function, induce competitive exclusion of pathogens, and modulate host immune responses. Recent probiotic advancements include engineering strains that disrupt V. cholerae biofilms and inhibit their virulence. Integrating probiotics with traditional cholera control measures could significantly enhance their effectiveness and provide a multifaceted approach to combating this persistent disease. This review aims to shed light on the potential of probiotics in revolutionizing cholera management and to offer insights into their application as both preventive and therapeutic tools in the fight against this enduring public health challenge.
Non-invasive brain stimulation in cognitive sciences and Alzheimer's disease
Authors: Carrarini Claudia , Pappalettera Chiara , Le Pera Domenica , Rossini Paolo Maria
Published: January 2025

Over the last four decades, non-invasive brain stimulation techniques (NIBS) have significantly gained interest in the fields of cognitive sciences and dementia care, including neurorehabilitation, for its emerging potential in increasing the insights over brain functions and in boosting residual cognitive functions. In the present paper, basic physiological and technical mechanisms and different applications of NIBS were reviewed and discussed to highlight the importance of NIBS in multidisciplinary and translational approaches in clinical and research settings of cognitive sciences and neurodegenerative diseases, especially in Alzheimer's disease. Indeed, NIBS strategies may represent a promising opportunity to increase the potential of neuromodulation as efficacious interventions for individualized patients care.
MEPFeatX—automated feature extraction of motor-evoked potentials in transcranial magnetic stimulation
Authors: Nguyen Dao T. A. , Säisänen Laura , Kallioniemi Elisa , Karjalainen Pasi A. , Rissanen Saara M. , Julkunen Petro
Published: January 2025

Motor evoked potentials (MEPs) are an important measure in transcranial magnetic stimulation (TMS) when assessing neuronal excitability in clinical diagnostics related to motor function, as well as in neuroscience research. However, manual feature extraction from large datasets can be time-consuming and prone to human error, and valuable features, such as MEP polyphasia and duration, are often neglected. Several packages have been developed to simplify the process; however, they are often tailored to specific studies or are not accessible. Here, we introduce MEPFeatX, a verified MATLAB package designed for automated and comprehensive MEP feature extraction across a wide range of stimulation paradigms. MEPFeatX is designed and documented for easy integration into any MEP analysis pipeline. Primed templates for specific paradigms, as well as additional analysis coded in R language, are also provided. Thus, MEPFeatX provides its users with a comprehensive and accurate set of MEP features, along with their visuals, facilitating quick and reliable MEP analysis in TMS studies.
Association between body esteem and sugar-sweetened beverage intake among Chinese undergraduate students: a cross-sectional study
Authors: Zhu Jiawen , Zhu Yuanyuan , Zhao Zihe , Huang Qianling , Liu Changju , Zeng Zhi
Published: January 2025

Background

High intake of sugar-sweetened beverages has been linked to a range of physical, psychological, and emotional issues. Although there were various factors influencing sugar-sweetened beverage intake, the relationship between body esteem and sugar-sweetened beverage intake remains unclear. This study aimed to investigate the association between three dimensions of body esteem (body esteem-appearance, body esteem-attribution, and body esteem-weight) and the likelihood of high sugar-sweetened beverage intake.

Methods

A cross-sectional study was conducted among undergraduate students at Nanjing University of Chinese Medicine. Logistic regression analyses were used to assess the association between the three dimensions of body esteem and the risk of high sugar-sweetened beverage intake. Additionally, restricted cubic splines and subgroup analyses were implemented to further explore the associations.

Results

A total of 969 participants were included in the study, with 771 females (79.6%). The mean age of the participants was 20.07 years (standard deviation [SD] = 1.65). After adjusting for covariates, body esteem-appearance was found to be negatively associated with high sugar-sweetened beverage intake (OR = 0.962, 95% CI = 0.935–0.989, p = 0.007), while body esteem-attribution was positively associated with high sugar-sweetened beverage intake (OR = 1.091, 95% CI = 1.046–1.139, p < 0.001). However, no significant association was found between body esteem-weight and high sugar-sweetened beverage intake (p = 0.781). Restricted cubic spline plots showed no non-linear associations between any dimensions of body esteem and the risk of high sugar-sweetened beverage intake (p-nonlinear was 0.912, 0.225, 0.109, respectively). Subgroup analyses revealed no significant interactions.

Conclusion

These findings underscored the significance of targeted health promotion strategies and provided references for educational institutions or governmental bodies to steer undergraduate beverage consumption toward healthier patterns.
Application value of different imaging methods in the early diagnosis of small hepatocellular carcinoma: a network meta-analysis
Authors: Dong Jian , Wang Zhen , Wang Si-Rui , Zhao Huan , Li Jun , Ma Ting
Published: January 2025

Objective

To determine the diagnostic value of ultrasound, multi-phase enhanced computed tomography, and magnetic resonance imaging of small hepatocellular carcinoma.

Methods

Experimental studies on diagnosing small hepatocellular carcinoma in four databases: PubMed, Cochrane Library, Web of Science, and Embase, were comprehensively searched from October 2007 to October 2024. Relevant diagnostic accuracy data were extracted and a Bayesian model that combined direct and indirect evidence was used for analysis.

Results

16 original studies were included and data from 2,447 patients were collated to assess the diagnostic value of 10 different methods. The methodological quality of the included studies was good and there was no obvious publication bias. The pooled DOR of all diagnostic methods was 19.61, which was statistically significant (I2 = 76.0%, P < 0.01, 95% CI:13.30 - 28.92). Normal US + CEUS + ultrasonic elastic imaging had the highest specificity (92.9), accuracy (93.6), and positive predictive value (94.4). Unenhanced MRI + Contrast-enhanced MRI had the highest sensitivity (96.6) and negative predictive value (96.6), but specificity (12.5) and positive predictive value (34.4) were extremely poor. Contrast-enhanced MRI had the highest diagnostic value in individual imaging methods (sensitivity: 66, specificity: 55.5, accuracy: 67.9, positive predictive value: 64.4, negative predictive value: 66.5). There was significant inconsistency and high heterogeneity in this study.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024507883.
Clinical follow-up of 2 families with glomerulopathy caused by COQ8B gene variants and literature review
Authors: Zhang Lei , Hall Gentzon , Han Peitong , Li Chunzhen , Cui Jieyuan
Published: January 2025

Background

Primary coenzyme Q10 (CoQ10) deficiency is an autosomal recessive genetic disease caused by mitochondrial dysfunction. Variants in Coenzyme Q8B (COQ8B) can cause primary CoQ10 deficiency. COQ8B-related glomerulopathy is a recently recognized glomerular disease that most often presents as steroid-resistant nephrotic syndrome (SRNS) in childhood. The disease often progresses to kidney failure and the renal histopathology is most commonly focal segmental glomerulosclerosis (FSGS).

Methods

Four SRNS cases (2 females and 2 males) from 2 unrelated families who were followed clinically for nearly 3 years. Clinical exome testing and analyses were performed by MyGenostics Laboratory in China to evaluate unexplained proteinuria given the strong family history of glomerular disease and histologic evidence of SRNS. Pathogenic variants were identified in COQ8B in the exome studies and confirmed by direct sequencing.

Results

Clinical exome sequencing revealed biallelic variants of the COQ8B gene in 2 families. In the Family 1, the oldest of three affected siblings died of renal failure at 11 years of age. Based on the results of genetic testing which identified a homozygous variant of COQ8B, the other two affected siblings with mild proteinuria and normal renal function were treated with CoQ10 oral supplementation at an early stage. Coenzyme Q10 treatment was effective in reducing proteinuria levels in both patients from Family 1 over the first 6 months and the two patients still have low-level proteinuria and normal renal function at nearly three years. In Family 2, clinical exome sequencing revealed a compoundheterozygous variants of COQ8B in a patient with biopsy- proven FSGS. His disease was unresponsive to prior treatment with glucocorticoids and cyclosporine. Oral CoQ10 was initiated based on his genetic diagnosis and was it was effective in reducing proteinuria over the first 5 months months of therapy. However after 1 year, his disease progressed tokidney failure. Kidney transplantation was performed at 5 years of age and his condition has been stable without rejection and no recurrence of disease.

Conclusions

COQ8B gene variant-related glomerulopathy often presents as SRNS without obvious extrarenal manifestations. The histopathology is mainly FSGS and follows an autosomal recessive mode of inheritance. Some patients may benefit from early coenzyme Q10 supplementation. For patients whose disease progresses to kidney failure, kidney transplantation can be an effective treatment. For children with unexplained proteinuria and abnormal renal function, genetic testing should be performed early in the course of disease to guide therapy where possible and improve prognosis.