Drug Development.

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the formation of amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFTs) composed of tau aggregates. Research in animal models has generated hypotheses on the underlying mechanisms of the interaction between Aβ and tau pathology. In support of this interaction, results from clinical trials have shown that treatment with anti-Aβ monoclonal antibodies (mAbs) affects tau pathology.

Drug Development.

Background: Developing drugs for treating Alzheimer's disease (AD) has been extremely challenging and costly due to limited knowledge on underlying biological mechanisms and therapeutic targets. Repurposing drugs or their combination has shown potential in accelerating drug development due to the reduced drug toxicity while targeting multiple pathologies.

Method: To address the challenge in AD drug development, we developed a multi-task machine learning pipeline to integrate a comprehensive knowledge graph on biological/pharmacological interactions and multi-level evidence on drug efficacy, to identify repurposable drugs and their combination candidates RESULT: Using the drug embedding from the heterogeneous graph representation model, we ranked drug candidates based on evidence from post-treatment transcriptomic patterns, mechanistic efficacy in preclinical models, population-based treatment effect, and Phase 2/3 clinical trials.

Drug Development.

Background: Alzheimer's disease (AD) is complex in pathogenesis and related to aging biology, especially in late-onset AD. We identified a novel synthetic curcumin analog TML-6 through the platform of 6 biomarkers of anti-aging, anti-inflammation, and anti-Aβ as the potential AD drug candidate. TML-6 exhibits multi-target effects on AD pathogenesis, including the activation of NrF-2, the regulation of autophagic machinery through mTOR, the inhibition of APP synthesis and reduction of Aβ, the upregulation of ApoE, and the inhibition of microglial activation.

Drug Development.

Background: SHIP1 is a phosphatidyl inositol phosphatase encoded by INPP5D, which has been identified as a risk gene for Alzheimer's disease (AD). SHIP1 is expressed in microglia, the resident macrophage in brain. It is a complex, multidomain protein that acts as a negative regulator downstream from TREM2.

Drug Development.

Real-world data on the uptake, effectiveness and safety of new diagnostics and disease-modifying (DMT) treatments for Alzheimer's Disease (AD) are imperative. This can be achieved through patient registries. A major challenge is how to embed registry data capture into routine clinical practice.

Drug Development.

Background: Microglial activation is one of the neuropathological hallmarks of Alzheimer's disease (AD). Evidence suggest that chronic activation of microglia cause neuroinflammation and neuronal injuries, contributing to cognitive impairment. Therefore, modulation of microglial pathway like CSF-1R represents an attractive therapeutic strategy.

Dementia Care Research and Psychosocial Factors.

Background: A potential mechanism underpinning the cognitive benefits from physical activity and aerobic exercise is cardiorespiratory fitness (CRF). Greater cardiorespiratory fitness (CRF) was associated with better executive function, short-term memory, and global cognition in older adults without cognitive impairment. Sex differences in CRF has been established in adults.

Dementia Care Research and Psychosocial Factors.

Background: The deficit of unawareness of cognitive impairment (cognitive anosognosia) is known to be associated with adverse health outcomes, caregiver burden, and worse cognitive outcomes. A better understanding of cognitive self-awareness and the ability to self-judge cognitive performance among the general population would enable a rational design of cognitive screening and improve how subjective cognitive decline and self-reported errors at tasks like medication administration are interpreted.

Method: Participants were enrolled in the Framingham Heart Study, which is a community-based cohort with three generations of participants.

Dementia Care Research and Psychosocial Factors.

Background: Almost all primary care providers (PCPs) believe screening for mild cognitive impairment (MCI) and dementia in older patients is important. However, there are significant barriers in primary care, including low provider confidence in their assessment skills, time constraints, competing priorities, and poor financial incentives. Consequently, PCPs report conducting cognitive assessments for less than half of patients over 60 years of age.

Dementia Care Research and Psychosocial Factors.

Background: Approximately 25% of adults 65+ are socially isolated. Social isolation (i.e.

Dementia Care Research and Psychosocial Factors.

Background: The global increase in dementia cases underscores the need for community-based services, particularly for older adults who spend significant time in their neighborhoods. This context profoundly influences cognitive function and quality of life, especially in those at high risk of cognitive impairment. Despite its importance, neighborhood cohesion has not been extensively studied in this group.

Impact of Heart Transplant Allocation Changes on Waitlist Mortality and Clinical Practice in Pediatric and Adult Patients With Congenital Heart Disease and Cardiomyopathy.

Background: The United Network of Organ Sharing made changes to the priority for allocation of hearts for transplantation (HT) in 2016 for pediatric patients and 2018 for adult patients. Although recent work has evaluated the impact of the revised allocation systems on mechanical circulatory support practices and waitlist outcomes, there are limited data that focus more specifically on the impact of the allocation changes on patients with congenital heart disease (CHD) or cardiomyopathy and how these relationships might differ in pediatric and adult patients.

Methods: The United Network of Organ Sharing database was queried for pediatric (<18 years of age) and adult (18-50 years of age) patients with a CHD or cardiomyopathy diagnosis listed for HT.

A Novel Prognostic Risk Model Based on Oxidative Stress to Predict Survival and Improve Treatment Strategies in Stomach Adenocarcinoma.

Background: Stomach adenocarcinoma (STAD) is the fifth most common tumor worldwide, imposing a significant disease burden on populations, particularly in Asia. Oxidative stress is well-known to play an essential role in the occurrence and progression of malignancies. Our study aimed to construct a prediction model by exploring the correlation between oxidative stress-related genes and the prognosis of patients with STAD.

Precise Manipulation on the Structural Defects of Poly (Triazine Imide) Single Crystals for Efficient Photocatalytic Overall Water Splitting.

Conjugated polymers, represented by polymeric carbon nitrides (PCNs), have risen to prominence as new-generation photocatalysts for overall water splitting (OWS). Despite considerable efforts, achieving highly crystalline PCNs with minimal structural defects remains a great challenge, and it is also difficult to examine the exact impact of complex defect states on OWS process, which largely limits their quantum efficiency. Herein, we devise a 'in-situ salt flux' assisted copolymerization protocol by using nitrogen-rich and nitrogen-deficient monomers to precisely manipulate the structural defects of poly (triazine imide) (PTI) single crystals.

Tumor-Educated Platelets lncRNA-STARD4-AS1 and ELOA-AS1 as Potential Novel Biomarkers for the Early Diagnosis of Non-Small Cell Lung Cancer.

Purpose: (Tumor-educated platelets) TEPs have emerged as active players in all steps of tumorigenesis, confrontation of platelets with tumor cells via transfer of tumor-associated biomolecules and results in the sequestration of such biomolecules. The current study was aimed to examine whether TEPs lncRNA-STARD4-AS1 and ELOA-AS1 might be potential biomarkers for NSCLC.

Materials And Methods: TEPs were obtained by low-speed centrifugation.

Enhancement of Interferon-γ Secretion by Extract Supplementation After Exhaustive Endurance Exercise in Healthy Men: A Double-blind, Placebo-controlled Trial.

To investigate the effects of 12-week extract supplementation on immune responses and inflammatory cytokines after exhaustive endurance exercise (EEE), emphasizing its novel focus on peripheral blood mononuclear cells (PBMCs) cytokine secretion and the implications of interferon-γ (IFN-γ) as a marker for immune modulation. Twenty healthy men were recruited and assigned into maca and placebo groups using a matched-pair design based on their maximal oxygen consumption (V̇O). All participants consumed 2.

Lipoprotein(a) and Atrial Fibrillation: Mechanistic Insights and Therapeutic Approaches.

Elevated lipoprotein(a) [Lp(a)] levels are increasingly recognized as a significant risk factor for cardiovascular diseases and may also contribute to atrial fibrillation (AF). This review investigated the indirect mechanisms through which Lp(a) may influence AF, including proatherogenic, prothrombotic, and proinflammatory pathways. Traditional lipid-lowering therapies, such as lifestyle modifications and statins, have limited effects on Lp(a) levels.

Comparison of Catheter Ablation in Patients with Paroxysmal Non-valvular Atrial Fibrillation and Heart Failure with Preserved Ejection Fraction.

The efficacy of radiofrequency ablation (RFA) in patients with atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) has been established, but the efficacy and safety of cryoballoon ablation (CBA) and pulsed field ablation (PFA) remain unclear. This retrospective cohort study included 223 patients with paroxysmal non-valvular AF and HFpEF who underwent their first AF ablation between January 2017 and December 2021 and were divided into RFA (n = 77), CBA (n = 127), and PFA (n = 19) groups. After a mean follow-up of 11.

Hyperbaric oxygen therapy attenuates brain radiation-induced cognitive deficits in rats.

Effective therapies for cognitive impairments induced by brain irradiation are currently lacking. This study investigated the therapeutic potential of hyperbaric oxygen therapy (HBOT) for radiation-induced brain injury in a randomized controlled experimental model using adult male Wistar rats. Adult male Wistar rats were divided into four experimental groups: 0 Gy whole brain radiotherapy (WBRT) with normal baric air (NBA) treatment, 0 Gy WBRT with HBOT, 10 Gy WBRT with NBA, and 10 Gy WBRT with HBOT.

The Cyclin-Dependent Kinase 8 Inhibitor E966-0530-45418 Attenuates Pulmonary Fibrosis and .

Pulmonary fibrosis (PF) is a high-mortality lung disease with limited treatment options, highlighting the need for new therapies. Cyclin-dependent kinase 8 (CDK8) is a promising target due to its role in regulating transcription via the TGF-β/Smad pathway, though CDK8 inhibitors have not been thoroughly studied for PF. This study aims to evaluate the potential of E966-0530-45418, a novel CDK8 inhibitor, in mitigating PF progression and explores its underlying mechanisms.

Fibroblasts in heterotopic ossification: mechanisms and therapeutic targets.

Heterotopic ossification (HO) refers to the abnormal formation of bone in non-skeletal tissues. Fibroblasts have traditionally been viewed as stationary cells primarily responsible for producing extracellular matrix during tissue repair and fibrosis. However, recent discoveries regarding their plasticity-encompassing roles in inflammation, extracellular matrix remodeling, and osteogenesis-highlight their potential as key contributors to the development of HO.

Uncovering the Role of in Prostate Cancer: Insights from Genetic and Expression Analyses.

Biochemical recurrence (BCR) is a critical concern in prostate cancer management; however, its underlying genetic determinants remain poorly understood. The () gene family is involved in cellular detoxification and biosynthetic processes and has been implicated in various cancers. This study investigated the association between the family members and prostate cancer recurrence.

Third generation vs first generation EGFR-TKIs in the first line treatment for EGFR-mutated locally advanced or metastatic non-small cell lung cancer: a meta-analysis based on randomized controlled trials.

The prevailing belief is that third-generation tyrosine kinase inhibitors (TKIs) targeting the epidermal growth factor receptor (EGFR) (TGET) outperform first-generation EGFR-TKIs (FGET) in managing advanced-stage EGFR-mutated non-small cell lung cancer (NSCLC). However, this standpoint lacks substantiation in evidence-based medicine. Therefore, this meta-analysis was conducted to compare the efficacy and adverse effects (AEs) of these two categories.

Single-cell analysis unveils cell subtypes of acral melanoma cells at the early and late differentiation stages.

Background: Melanoma, a malignant neoplasm originating from melanocytes, is a form of skin cancer with rapidly increasing global incidence, often exacerbated by UV radiation[1]. Particularly, acral melanoma, characterized by its swift metastasis and poor prognosis, underscores the significance of further research into its heterogeneity. Single-cell sequencing has been widely utilized in the study of tumor heterogeneity; however, research related to melanoma remains to be further refined.