Genome-wide association neural networks identify genes linked to family history of Alzheimer's disease.

Augmenting traditional genome-wide association studies (GWAS) with advanced machine learning algorithms can allow the detection of novel signals in available cohorts. We introduce "genome-wide association neural networks (GWANN)" a novel approach that uses neural networks (NNs) to perform a gene-level association study with family history of Alzheimer's disease (AD). In UK Biobank, we defined cases (n = 42 110) as those with AD or family history of AD and sampled an equal number of controls.

Customizing Tacrolimus Dosing in Kidney Transplantation: Focus on Pharmacogenetics.

Different polymorphisms in genes encoding metabolizing enzymes and drug transporters have been associated with tacrolimus pharmacokinetics. In particular, studies on CYP3A4 and CYP3A5, and their combined cluster have demonstrated their significance in adjusting tacrolimus dosing to minimize under- and overexposure thereby increasing the proportion of patients who achieve tacrolimus therapeutic target. Many factors influence the pharmacokinetics of tacrolimus, contributing to inter-patient variability affecting individual dosing requirements.

End-procedural adherence to recommended hemodynamic targets does not improve the outcome of elective tips in cirrhotic patients.

Background Aims: In clinical practice, the reduction of porto-caval pressure gradient (PCPG) following trans-jugular intra-hepatic porto-systemic shunt (TIPS) does not always meet the recommendation of current guidance. We evaluated the impact of different degrees of PCPG reduction, measured at the end of an elective TIPS, on ascites control, recurrence of portal hypertension-related bleeding (PHRB) and survival.

Approach And Results: Cirrhotic patients receiving TIPS for refractory ascites (RA) or for the secondary prophylaxis of PHRB were consecutively enrolled.

Advancing Delirium Treatment Trials in Older Adults: Recommendations for Future Trials From the Network for Investigation of Delirium: Unifying Scientists (NIDUS).

Objectives: To summarize the delirium treatment trial literature, identify the unique challenges in delirium treatment trials, and formulate recommendations to address each in older adults.

Design: A 39-member interprofessional and international expert working group of clinicians (physicians, nurses, and pharmacists) and nonclinicians (biostatisticians, epidemiologists, and trial methodologists) was convened. Four expert panels were assembled to explore key subtopics (pharmacological/nonpharmacologic treatment, methodological challenges, and novel research designs).

Endothelial-secreted Endocan activates PDGFRA and regulates vascularity and spatial phenotype in glioblastoma.

Extensive neovascularization is a hallmark of glioblastoma (GBM). In addition to supplying oxygen and nutrients, vascular endothelial cells provide trophic support to GBM cells via paracrine signaling. Here we report that Endocan (ESM1), an endothelial-secreted proteoglycan, confers enhanced proliferative, migratory, and angiogenic properties to GBM cells and regulates their spatial identity.

Advancing Delirium Treatment Trials in Older Adults: Recommendations for Future Trials From the Network for Investigation of Delirium: Unifying Scientists (NIDUS).

Objectives: To summarize the delirium treatment trial literature, identify the unique challenges in delirium treatment trials, and formulate recommendations to address each in older adults.

Design: A 39-member interprofessional and international expert working group of clinicians (physicians, nurses, and pharmacists) and nonclinicians (biostatisticians, epidemiologists, and trial methodologists) was convened. Four expert panels were assembled to explore key subtopics (pharmacological/nonpharmacologic treatment, methodological challenges, and novel research designs).

Anaphylaxis Induced by Multiple Sensitization With Hymenoptera Venom:Report of One Case.

Hymenoptera venom-sensitized patients may experience systemic reactions,and severe patients may even present life-threatening symptoms such as collapse and syncope.Here we report a case of anaphylaxis triggered by multiple sensitization with Hymenoptera venom.Clinical diagnosis and allergen testing showed that the patient developed anaphylaxis to wasp and/or fire ant venom.

Multi‑omics identification of a novel signature for serous ovarian carcinoma in the context of 3P medicine and based on twelve programmed cell death patterns: a multi-cohort machine learning study.

Background: Predictive, preventive, and personalized medicine (PPPM/3PM) is a strategy aimed at improving the prognosis of cancer, and programmed cell death (PCD) is increasingly recognized as a potential target in cancer therapy and prognosis. However, a PCD-based predictive model for serous ovarian carcinoma (SOC) is lacking. In the present study, we aimed to establish a cell death index (CDI)-based model using PCD-related genes.

The Role of Pharmacometrics in Advancing the Therapies for Autoimmune Diseases.

Autoimmune diseases (AIDs) are a group of disorders in which the immune system attacks the body's own tissues, leading to chronic inflammation and organ damage. These diseases are difficult to treat due to variability in drug PK among individuals, patient responses to treatment, and the side effects of long-term immunosuppressive therapies. In recent years, pharmacometrics has emerged as a critical tool in drug discovery and development (DDD) and precision medicine.

Advances in Nanotheranostic Systems for Concurrent Cancer Imaging and Therapy: An Overview of the Last 5 Years.

The rapid development of nanotechnology during the last two decades has created new opportunities to design and generate more advanced nanotheranostics with diversified capabilities for diagnosis, drug delivery, and treatment response monitoring in a single platform. To date, several approaches have been employed in order to develop nanotheranostics. The purpose of this review is to briefly discuss the key components of nanotheranostic systems, to present the conventional and upcoming imaging and therapeutic modalities that employ nanotheranostic systems, and to evaluate recent progress in the field of cancer nanotheranostic systems in the past five years (2020-2024).

Metabolic Biomarkers of Liver Failure in Cell Models and Patient Sera: Toward Liver Damage Evaluation In Vitro.

Recent research has concentrated on the development of suitable in vitro cell models for the early identification of hepatotoxicity during drug development in order to reduce the number of animal models and to obtain a better predictability for hepatotoxic reactions in humans. The aim of the presented study was to identify translational biomarkers for acute liver injury in human patients that can serve as biomarkers for hepatocellular injury in vivo and in vitro in simple cell models. Therefore, 188 different metabolites from patients with acute-on-chronic liver failure before and after liver transplantation were analyzed with mass spectrometry.

Revolutionizing Neuroimmunology: Unraveling Immune Dynamics and Therapeutic Innovations in CNS Disorders.

Neuroimmunology is reshaping the understanding of the central nervous system (CNS), revealing it as an active immune organ rather than an isolated structure. This review delves into the unprecedented discoveries transforming the field, including the emerging roles of microglia, astrocytes, and the blood-brain barrier (BBB) in orchestrating neuroimmune dynamics. Highlighting their dual roles in both repair and disease progression, we uncover how these elements contribute to the intricate pathophysiology of neurodegenerative diseases, cerebrovascular conditions, and CNS tumors.

Association of Computed Tomography Scan-Assessed Body Composition with Immune and PI3K/AKT Pathway Proteins in Distinct Breast Cancer Tumor Components.

This hypothesis-generating study aims to examine the extent to which computed tomography-assessed body composition phenotypes are associated with immune and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathways in breast tumors. A total of 52 patients with newly diagnosed breast cancer were classified into four body composition types: adequate (lowest two tertiles of total adipose tissue [TAT]) and highest two tertiles of total skeletal muscle [TSM] areas); high adiposity (highest tertile of TAT and highest two tertiles of TSM); low muscle (lowest tertile of TSM and lowest two tertiles of TAT); and high adiposity with low muscle (highest tertile of TAT and lowest tertile of TSM). Immune and PI3K/AKT pathway proteins were profiled in tumor epithelium and the leukocyte-enriched stromal microenvironment using GeoMx (NanoString).

Studying Rare Movement Disorders: From Whole-Exome Sequencing to New Diagnostic and Therapeutic Approaches in a Modern Genetic Clinic.

Rare movement disorders often have a genetic etiology. New technological advances have increased the odds of achieving genetic diagnoses: next-generation sequencing (NGS) (whole-exome sequencing-WES; whole-genome sequencing-WGS) and long-read sequencing (LRS). In 2017, we launched a WES program for patients with rare movement disorders of suspected genetic etiology.

Health and Liver Diagnostic Markers Influencing Glycemia in Subjects with Prediabetes: Preview Study.

Introduction: Glucose homeostasis may be dependent on liver conditions and influence health-related markers and quality of life (QoL) objective measurements. This study aimed to analyze the interactions of glycemia with liver and health status in a prediabetic population.

Subjects And Methods: This study included 2220 overweight/obese prediabetics from the multinational PREVIEW project.

Exploring Immune Cell Infiltration and Small Molecule Compounds for Ulcerative Colitis Treatment.

Background/objectives: Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) with a relapsing nature and complex etiology. Bioinformatics analysis has been widely applied to investigate various diseases. This study aimed to identify crucial differentially expressed genes (DEGs) and explore potential therapeutic agents for UC.

"Beyond the Knife"-Applying Theranostic Technologies to Enhance Outcomes in Neurosurgical Oncology.

The current standard of care for brain tumor management includes maximal safe surgical resection followed by concurrent chemotherapy and radiation therapy. Recent advances in image-guided surgical techniques have enhanced the precision of tumor resections, yet there remains a critical need for innovative technologies to further improve patient outcomes. Techniques such as fluorescence image-guided neurosurgery in combination with stereotactic radiosurgery have improved outcomes for patients with brain tumors.

Mitochondrial Dysfunction as a Biomarker of Illness State in Bipolar Disorder: A Critical Review.

Mitochondria are organelles involved in different cellular functions, especially energy production. A relationship between mitochondrial dysfunction and mood disorders, especially bipolar disorder (BD), has been reported in the scientific literature, which suggests altered energy production and higher levels of oxidative stress compared to healthy controls. Specifically, in BD, the hypothesis of a biphasic pattern of energy availability has been postulated according to mood states.

Decoding Schizophrenia: How AI-Enhanced fMRI Unlocks New Pathways for Precision Psychiatry.

Schizophrenia, a highly complex psychiatric disorder, presents significant challenges in diagnosis and treatment due to its multifaceted neurobiological underpinnings. Recent advancements in functional magnetic resonance imaging (fMRI) and artificial intelligence (AI) have revolutionized the understanding and management of this condition. This manuscript explores how the integration of these technologies has unveiled key insights into schizophrenia's structural and functional neural anomalies.

Isolation of Plasma Extracellular Vesicles for High-Depth Analysis of Proteomic Biomarkers in Metastatic Castration-Resistant Prostate Cancer Patients.

: Prostate cancer treatment has been revolutionized by targeted therapies, including PARP inhibitors, checkpoint immunotherapies, and PSMA-targeted radiotherapies. Despite such advancements, accurate patient stratification remains a challenge, with current methods relying on genomic markers, tissue staining, and imaging. Extracellular vesicle (EV)-derived proteins offer a novel non-invasive alternative for biomarker discovery, holding promise for improving treatment precision.

Identification of Transcriptional Regulators of Immune Evasion Across Cancers: An Alternative Immunotherapeutic Strategy for Cholangiocarcinoma.

Background: Cancer immune evasion is a multifaceted process that synchronizes pro-tumoral immune infiltration, immunosuppressive inflammation, and inhibitory immune checkpoint expression (IC). Current immunotherapies combat this issue by reinstating immunosurveillance of tumors; however, it benefits a limited patient population. Thus, a more effective immunotherapeutic strategy is warranted to cater to specific patient populations.

Inbreeding and Gallbladder Cancer Risk: Homozygosity Associations Adjusted for Indigenous American Ancestry, BMI, and Genetic Risk of Gallstone Disease.

Latin Americans have a rich genetic make-up that translates into heterogeneous fractions of the autosomal genome in runs of homozygosity (F) and heterogeneous types and proportions of indigenous American ancestry. While autozygosity has been linked to several human diseases, very little is known about the relationship between inbreeding, genetic ancestry, and cancer risk in Latin Americans. Chile has one of the highest incidences of gallbladder cancer (GBC) in the world, and we investigated the association between inbreeding, GBC, gallstone disease (GSD), and body mass index (BMI) in 4029 genetically admixed Chileans.

Polyphenol-Derived Microbiota Metabolites and Cardiovascular Health: A Concise Review of Human Studies.

Polyphenols, plant-derived secondary metabolites, play crucial roles in plant stress responses, growth regulation, and environmental interactions. In humans, polyphenols are associated with various health benefits, particularly in cardiometabolic health. Despite growing evidence of polyphenols' health-promoting effects, their mechanisms remain poorly understood due to high interindividual variability in bioavailability and metabolism.

Mechanisms of Autophagy in Ineffective Reperfusion After Ischemic Stroke.

Despite significant advancements in achieving high recanalization rates (80%-90%) for large vessel occlusions through mechanical thrombectomy, the issue of "futile recanalization" remains a major clinical challenge. Futile recanalization occurs when over half of patients fail to experience expected symptom improvement after vessel recanalization, often resulting in severe functional impairment or death. Traditionally, this phenomenon has been attributed to inadequate blood flow and reperfusion injury.