Search Results (275)

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome with increasing prevalence and substantial morbidity and mortality. Recent advances in pharmacotherapy have transformed its management. This review summarizes current evidence supporting the use of sodium–glucose cotransporter 2 inhibitors, non-steroidal mineralocorticoid receptor antagonists, and glucagon-like peptide-1 receptor agonists, alongside selected use of angiotensin receptor–neprilysin inhibitors. Emphasis is placed on early initiation of disease-modifying therapies, phenotypic tailoring, and comorbidity-targeted strategies, especially in obese and diabetic patients. Together, these approaches define a new era of guideline-directed, personalized care for patients with HFpEF. Full article

The emergence of anti-TNF agents has revolutionized the management of inflammatory bowel disease, yet a significant proportion of patients experience primary non-response or secondary loss of response due to immunogenicity. As the field of precision medicine advances, genetic predictors such as human leukocyte antigen (HLA) variants are gaining increasing attention. This review provides a comprehensive synthesis of current evidence on the role of HLA genotypes in inflammatory bowel disease susceptibility and disease behavior, with a focus on their mechanistic and clinical relevance in anti-TNF therapy. Special emphasis is placed on HLA-DQA1*05, a validated predictor of anti-drug antibody formation and reduced therapeutic durability. We explore the immunological basis of HLA-mediated immunogenicity, summarize pharmacogenetic and biomarker findings, and discuss how HLA typing may be integrated into treatment algorithms to improve patient stratification and long-term outcomes. As immunogenetics continues to inform clinical decision-making, understanding the interplay between HLA polymorphisms and therapeutic response offers new opportunities for biomarker-guided, personalized care in inflammatory bowel disease. Full article

Endometrial carcinoma (EC) is the most common gynaecological malignancy in developed nations, exhibiting significant molecular heterogeneity that impacts prognosis and treatment response, particularly in advanced or recurrent settings. Traditional classification is increasingly supplemented by molecular subtyping (POLE-ultramutated, MSI-high/dMMR, NSMP, p53-mutated/CNH), which provides crucial prognostic information and predicts benefit from immunotherapy. This review summarizes the landscape of predictive biomarkers for immune checkpoint inhibitor (ICI) therapy in EC, emphasizing a new therapeutic scenario for advanced and recurrent EC. Mismatch repair deficiency (dMMR) or high microsatellite instability (MSI-H), leading to high tumor mutational burden (TMB) and increased neoantigen production, is the most established predictor, resulting in FDA approvals for pembrolizumab and dostarlimab in this subgroup. POLE mutations also confer hypermutation and high immunogenicity, predicting a favorable ICI response. Other biomarkers, including PD-L1 expression and TMB, show variable correlation with response and require further standardization. The tumor immune microenvironment, including tumor-infiltrating lymphocytes (TILs), also influences treatment outcomes. Clinical trials have demonstrated significant survival benefits for ICIs combined with chemotherapy (e.g., dostarlimab/pembrolizumab + carboplatin/paclitaxel) in first-line settings, especially for dMMR/MSI-H EC, and for ICI combinations with targeted agents (e.g., lenvatinib + pembrolizumab) in previously treated patients. Integrating molecular classification and validated biomarkers is essential for optimizing patient selection and developing personalized immunotherapy strategies for EC. Full article

This proceedings summarize the presentations of the 14th Alcohol Hangover Research Group (AHRG) meeting, 11–13 April 2024 in Glasgow, UK. At this annual meeting, researchers and industry representatives discussed the current state of knowledge on the causes, consequences, and treatment of alcohol hangovers, networked, and established collaborations to conduct joint future research projects. At the 14th AHRG meeting, factors impacting the presence and severity of hangovers were discussed, such as having underlying diseases, daily diet, baseline mood and personality, new information on the pathology of the alcohol hangover, a mobile phone app to monitor alcohol consumption and hangovers, and various novel treatments. Full article

Sudden cardiac death (SCD) is a major public health concern, being a leading cause of death worldwide. SCD is particularly alarming for individuals with apparently good health, as it often occurs without preceding warning signs. Unfortunately, traditional autopsy methods frequently fail to identify the precise cause of death in these cases, highlighting the need for advanced techniques to elucidate underlying mechanisms. Recent advances in molecular biology over the past few years, particularly in proteomics, transcriptomics, and metabolomics techniques, have led to an expanded understanding of gene expression, protein activity, and metabolic changes, offering valuable insights into fatal cardiac events. Combining multi-omics methods with bioinformatics and machine learning algorithms significantly enhances our ability to uncover the processes behind lethal cardiac dysfunctions by identifying new useful biomarkers (like cardiac myosin-binding protein C, acylcarnitines, or microRNAs) to reveal molecular pathways linked to SCD. This narrative review summarizes the role of multi-omics approaches in forensic diagnosis by exploring current applications in unexplained cases and the benefits of integrating merged techniques in otherwise negative autopsies. We also discuss the potential for developing personalized and preventive forensic medicine, the technical limitations of currently available methods, and the ethical considerations arising from these advancements. Full article

Malignant diseases represent a major global health challenge and are among the leading causes of death worldwide. Accurate early diagnosis is essential for improving outcomes and combating these conditions effectively. Currently, the diagnosis of malignancies relies heavily on radiological imaging and pathological examinations, which are often invasive and not cost-effective. As such, there is a growing need for non-invasive and accessible methods to detect cancer in its early stages. Tumor markers—biomolecules whose levels increase in malignancy and can be measured in blood or other biological tissues and fluids—offer a promising tool. However, the sensitivity and specificity of currently available tumor markers are insufficient for early detection, limiting their use primarily to disease monitoring rather than diagnosis. While ongoing research continues to identify novel tumor markers, the development of more effective early detection strategies requires more than the discovery of new biomarkers. The continuous monitoring of patients and individuals with a high tumor risk and the personalization of tumor marker interpretation are also critical. In this review, we (i) summarize the most commonly used tumor markers, (ii) examine strategies for developing novel biomarkers, particularly through omics technologies, (iii) explore the potential of continuous monitoring using wearable biosensors for early tumor detection, and (iv) discuss approaches to personalizing tumor marker interpretation to support early diagnosis and improve treatment outcomes. Full article

Neural stem cells have shown great potential in the therapy of neurodegenerative diseases such as Parkinson’s disease (PD), because of their ability to differentiate into various types of neural cells and substitute for damaged neurons. Their clinical application is, however, impeded by limitations such as low survival rates following transplantation, low efficiency of differentiation, the potential for tumorigenesis, and the risk of immune rejection by the host. Adipose-derived stem cells (ADSCs) have become increasingly popular as an alternative tool in regenerative medicine due to their accessibility, multipotency, and low immunogenicity. The recent advance in inducing ADSCs into neural stem cell-like cells (iNSCs) opens up a new avenue for the treatment of PD by restoring dopaminergic neuron populations. Here, the biological characteristics, induction protocols, molecular mechanisms, and prospective applications of ADSCs in neural repair are summarized systematically. We also covered current technical challenges, such as differentiation protocol optimization and functional integration, and future perspectives, including biomaterial and gene editing applications to enhance ADSC-based therapies. With these challenges met, ADSCs hold excellent potential for advancing personalized and combination therapies for neurodegenerative diseases. Full article

Rheumatoid arthritis (RA) is a chronic autoimmune disease that has a serious impact on both human health and animal production. The gut microbiota is a large and complex symbiotic ecosystem in animals, and the imbalance of gut microbiota is closely related to the pathogenesis of numerous diseases, including RA. The interactions among the gut microbiota, intestinal barrier, and immune system play key roles in maintaining intestinal homeostasis and affecting the development of RA. Regulating intestinal flora and metabolites provides new ideas for the prevention and treatment of RA. Probiotics can regulate the balance of intestinal flora and metabolites, improve the immune environment, and provide novel therapeutic strategies against RA. In order to summarize the role of gut microbiota and metabolite remodeling in the development and management of RA, this review will elaborate on the role of intestinal flora imbalance in the pathogenesis of RA and assess prospective therapeutic approaches that target the gut flora. Understanding the interaction among intestinal flora, metabolites, and RA will help to clarify the pathogenesis of RA and develop innovative and personalized therapeutic interventions against chronic autoimmune diseases. Full article

Eosinophils are increasingly recognized as adaptable immune cells that exhibit diverse phenotypes and effector functions across different tissues and disease states. While they can induce pathology through degranulation and cytotoxic mediator release, eosinophils also fulfill regulatory and tissue repair roles. Advances in single-cell and spatial technologies have begun to reveal how microenvironmental cues (including cytokines, chemokines, and cell–cell interactions) shape eosinophil behavior in health and disease. These insights are critical for understanding why certain patients respond variably to therapies targeting eosinophils and related type 2 pathways. By dissecting eosinophil heterogeneity in real human tissues, researchers may identify new biomarkers, refine endotyping approaches, and develop more precise therapeutic strategies. This review summarizes emerging concepts of eosinophil biology in inflammatory conditions, highlights the impact of spatial context on eosinophil functions, and discusses the future of advanced phenotyping in guiding personalized treatments. Full article

Brain organoids are self-organized, three-dimensional (3D) aggregates derived from human embryonic stem cells, induced pluripotent stem cells, or primary organs with cell types and cellular architectures resembling those of the developing human brain. Recent studies have shown the use of region-specific brain organoids for modeling various diseases ranging from neurodevelopmental and neurodegenerative diseases to different brain cancers, which have numerous applications in fundamental research and the development of new drugs, personalized treatment, and regenerative medicine. Consequently, the use of brain organoids in drug discovery is complex and challenging and still an emerging area in this field. This review article summarizes the primary stem cells used in brain organoid generation, region-specific brain organoids, and the functional assays used in their characterization. In addition, we discuss the use of brain organoids in modeling neurodevelopmental and neurodegenerative diseases and pediatric brain cancers, as well as the application of organoids, assembloids, and tumoroids in cancer neuroscience. We further explore the recent advances in using brain organoids in high-throughput screening to improve their use for drug discovery. Full article

Abstractive summarization tasks are commonly without options for sentimental tendencies, which leads to a lack of summary personalization and a simplification of the understanding of the text content. Recognizing the crucial role of sentimental tendency in shaping reader interest and perception, such as prompting hopeful outlooks or critical evaluations, we introduce the summaries with multiple optional sentimental tendencies (SMOST) task, which involves generating summaries with various sentiment options and particularly benefits the news domain. Due to a scarcity of labeled data for sentiment-supervised summarization, we utilize sentiment sentences from original texts as positive samples in the training process, augmented with a prompt learning method. Our method achieves a better result on the CNN/DailyMail and XSum datasets regarding sentiment scores and has a small influence on the semantic information of summaries. Further analysis also shows that our method can present the different distributions of sentiment and semantic information on different datasets. Full article

Aging is the primary risk factor for chronic diseases such as cardiovascular disease, cancer, and dementia. However, chronological age alone fails to capture individual variability in aging trajectories and disease susceptibility. Recent advances in epigenetic clocks—DNA methylation-based models that estimate biological age—have opened new possibilities for personalized and preventive medicine. This review explores the clinical potential of epigenetic clocks and EpiScores, composite biomarkers that predict health risks and physiological status. We present a comparative evaluation of widely used epigenetic clocks, including Horvath, GrimAge, PhenoAge, and DunedinPACE, and summarize their predictive performance for mortality, cognitive decline, and cardiovascular outcomes. EpiScores linked to inflammation, glycemic control, and immunosenescence are highlighted as tools for stratified risk assessment. When integrated with multi-omics data and electronic health records, these measures enhance the precision of population health management. Special emphasis is placed on applications in longevity clinics and anti-aging clinics, community-based care, and national health checkup systems. We also explore global standardization efforts and ethical considerations, as well as Japan’s unique initiatives—including the “Aging Measurement” project at the Osaka-Kansai Expo 2025. Furthermore, we propose the development of a Global Health and Aging Index that integrates the biological, functional, and subjective dimensions of aging, aligned with the WHO concept of Intrinsic Capacity. In conclusion, epigenetic clocks and EpiScores represent transformative tools for shifting from reactive treatment to proactive health optimization, and from chronological to biological metrics in aging science and public health policy. Full article

Pregnancy induces significant physiologic changes that impact the cardiovascular system, potentially exacerbating pre-existing cardiac conditions or precipitating new illnesses. Pregnant patients with cardiac emergencies pose unique challenges, as standard interventions may pose risks to the developing fetus. This article aims to enhance emergency physicians’ confidence in managing pregnancy-related cardiac emergencies by providing a structured approach to initial evaluation and stabilization. We review eight common categories of pregnancy-associated cardiac illness: gestational hypertension and pre-eclampsia, cardiomyopathy, arrhythmias, valvular disease, aortopathies, congenital heart disease and pulmonary hypertension, coronary disease, and anticoagulation-related complications. For each condition, we summarize relevant pregnancy-specific pathophysiology and outline evidence-based, personalized emergency management strategies. Full article

Cardiovascular disease (CVD) remains the leading cause of death worldwide. Several factors are implicated in the pathogenesis of CVD, and efforts have been made to reduce traditional risks, yet CVD remains a complex burden. Notably, people living with HIV (PLWH) are twice as likely to develop CVD compared to persons without HIV (PWoH). Intensive statin therapy, the first-line treatment to prevent cardiovascular events, is effective at reducing morbidity and mortality. However, statin therapy has not reduced the overall prevalence of CVD. Despite antiretroviral therapy (ART), and new guidelines for statin use, PLWH have persistent elevation of inflammatory markers, which is suggested to be a bigger driver of future cardiovascular events than low-density lipoprotein. Herein, we have summarized the development of atherosclerosis and highlighted mouse models of atherosclerosis in the presence and absence of HIV. Since most mouse strains have several mechanisms that are atheroprotective, researchers have developed mouse models to study CVD using dietary and genetic manipulations. In evaluating the current methodologies for studying HIV-associated atherosclerosis, we have detailed the benefits of integrating multi-omics analyses, genetic manipulations, and immune cell profiling within mouse models. These advanced approaches significantly enhance our capacity to address critical gaps in understanding the immune mechanisms driving CVD, including in the context of HIV. Full article

In response to the global trend of population aging, the issue of providing elderly individuals suitable leisure and entertainment has become increasingly important. In this study, it aims to utilize artificial intelligence (AI) technology to offer the elderly with a healthy and enjoyable exercise and leisure experience. A human–machine interactive system is designed using computer vision, a subfield of AI, to promote positive physical adaptation for the elderly. The relevant literature on the needs of the elderly, technology, exercise, leisure, and AI techniques is reviewed. Case studies of interactive devices for exercise and leisure for the elderly, both domestically and internationally, are summarized to establish the prototype concept for system design. The proposed interactive exercise and leisure system is developed by integrating motion-sensing interfaces and real-time object detection using the YOLO algorithm. The system’s effectiveness is evaluated through questionnaire surveys and participant interviews, with the collected survey data analyzed statistically using IBM SPSS 26 and AMOS 23. Findings indicate that (1) AI technology provides new and enjoyable interactive experiences for the elderly’s exercise and leisure; (2) positive impacts are made on the elderly’s health and well-being; and (3) the system’s acceptance and attractiveness increase when elements related to personal experiences are incorporated into the system. Full article