Development and Validation of the Patient-Level Chinese Diabetes Outcome Model on Long-term Complications in Type 2 Diabetes: An Application of the Hong Kong Diabetes Register.

Objective: Patient-level simulation models, mainly developed in Western populations, capture complex interactions between risk factors and complications to predict the long-term effectiveness and cost-effectiveness of novel treatments and identify high-risk subgroups for personalized care. However, incidence of outcomes varies significantly by ethnicity and region. We used high-quality, patient-level register data to develop the Chinese Diabetes Outcomes Model (CDOM) for predicting incident and recurrent events in type 2 diabetes (T2D).

Astrocytic EphA4 signaling is important for the elimination of excitatory synapses in Alzheimer's disease.

Cell surface receptors, including erythropoietin-producing hepatocellular A4 (EphA4), are important in regulating hippocampal synapse loss, which is the key driver of memory decline in Alzheimer's disease (AD). However, the cell-specific roles and mechanisms of EphA4 are unclear. Here, we show that EphA4 expression is elevated in hippocampal CA1 astrocytes in AD conditions.

Transethnic analysis identifies SORL1 variants and haplotypes protective against Alzheimer's disease.

Introduction: The SORL1 locus exhibits protective effects against Alzheimer's disease (AD) across ancestries, yet systematic studies in diverse populations are sparse.

Methods: Logistic regression identified AD-associated SORL1 haplotypes in East Asian (N = 5249) and European (N = 8588) populations. Association analysis between SORL1 haplotypes and AD-associated traits or plasma biomarkers was conducted.

The noncoding circular RNA regulates synaptic development and experience-dependent plasticity in mouse visual cortex.

Circular RNAs (circRNAs) are a class of closed-loop, single stranded RNAs whose expression is particularly enriched in the brain. Despite this enrichment and evidence that the expression of circRNAs are altered by synaptic development and in response to synaptic plasticity , the regulation by and function of the majority of circRNAs in experience-dependent plasticity remain unexplored. Here, we employed transcriptome-wide analysis comparing differential expression of both mRNAs and circRNAs in juvenile mouse primary visual cortex (V1) following monocular deprivation (MD), a model of experience-dependent developmental plasticity.

Revisiting the concept of bout: associations of moderate-to-vigorous physical activity sessions and non-sessions with mortality.

Introduction: Current physical activity guidelines recommend 150 min of moderate-to-vigorous physical activity (MVPA) for health benefits, regardless of the pattern of MVPA. However, MVPA that occurs in sessions (MVPA-S) may have different health implications compared to MVPA that is not accumulated in sessions (MVPA-nonS). This study aimed to investigate the associations of MVPA-S and MVPA-nonS with mortality.

Using blood transcriptome analysis for Alzheimer's disease diagnosis and patient stratification.

Introduction: Blood protein biomarkers demonstrate potential for Alzheimer's disease (AD) diagnosis. Limited studies examine the molecular changes in AD blood cells.

Methods: Bulk RNA-sequencing of blood cells was performed on AD patients of Chinese descent (n = 214 and 26 in the discovery and validation cohorts, respectively) with normal controls (n = 208 and 38 in the discovery and validation cohorts, respectively).

A blood-based multi-pathway biomarker assay for early detection and staging of Alzheimer's disease across ethnic groups.

Introduction: Existing blood-based biomarkers for Alzheimer's disease (AD) mainly focus on its pathological features. However, studies on blood-based biomarkers associated with other biological processes for a comprehensive evaluation of AD status are limited.

Methods: We developed a blood-based, multiplex biomarker assay for AD that measures the levels of 21 proteins involved in multiple biological pathways.

Temporal associations of diabetes-related complications with health-related quality of life decrements in Chinese patients with type 2 diabetes: A prospective study among 19 322 adults-Joint Asia Diabetes Evaluation (JADE) register (2007-2018).

Background: Patients with type 2 diabetes (T2D) are at high risk of developing multiple complications, affecting their health-related quality of life (HRQoL). Existing studies only considered impact of complication on HRQoL in the year of occurrence but not its residual impacts in subsequent years. We investigated temporal impacts of diabetes-related complications on HRQoL in a 12-year prospective cohort of ambulatory Chinese patients with T2D enrolled in the clinic-based Joint Asia Diabetes Evaluation (JADE) Register.

Neuronal γ-secretase regulates synaptic functions via cholesterol homeostasis.

In this issue of Neuron, Essayan-Perez and Südhof demonstrate roles for γ-secretase in the regulation of synaptic functions in human neurons. Chronic attenuation of γ-secretase activity increases synapse formation but decreases neurotransmission (i.e.

The VCAM1-ApoE pathway directs microglial chemotaxis and alleviates Alzheimer's disease pathology.

In Alzheimer's disease (AD), sensome receptor dysfunction impairs microglial danger-associated molecular pattern (DAMP) clearance and exacerbates disease pathology. Although extrinsic signals, including interleukin-33 (IL-33), can restore microglial DAMP clearance, it remains largely unclear how the sensome receptor is regulated and interacts with DAMP during phagocytic clearance. Here, we show that IL-33 induces VCAM1 in microglia, which promotes microglial chemotaxis toward amyloid-beta (Aβ) plaque-associated ApoE, and leads to Aβ clearance.

Receptor-ligand interaction controls microglial chemotaxis and amelioration of Alzheimer's disease pathology.

Microglia maintain brain homeostasis through their ability to survey and phagocytose danger-associated molecular patterns (DAMPs). In Alzheimer's disease (AD), microglial phagocytic clearance regulates the turnover of neurotoxic DAMPs including amyloid beta (Aβ) and hyperphosphorylated tau. To mediate DAMP clearance, microglia express a repertoire of surface receptors to sense DAMPs; the activation of these receptors subsequently triggers a chemotaxis-to-phagocytosis functional transition in microglia.

An IL1RL1 genetic variant lowers soluble ST2 levels and the risk effects of APOE-ε4 in female patients with Alzheimer's disease.

Changes in the levels of circulating proteins are associated with Alzheimer's disease (AD), whereas their pathogenic roles in AD are unclear. Here, we identified soluble ST2 (sST2), a decoy receptor of interleukin-33-ST2 signaling, as a new disease-causing factor in AD. Increased circulating sST2 level is associated with more severe pathological changes in female individuals with AD.

Deep learning-based polygenic risk analysis for Alzheimer's disease prediction.

Background: The polygenic nature of Alzheimer's disease (AD) suggests that multiple variants jointly contribute to disease susceptibility. As an individual's genetic variants are constant throughout life, evaluating the combined effects of multiple disease-associated genetic risks enables reliable AD risk prediction. Because of the complexity of genomic data, current statistical analyses cannot comprehensively capture the polygenic risk of AD, resulting in unsatisfactory disease risk prediction.

Gender-associated cardiometabolic risk profiles and health behaviors in patients with type 2 diabetes: a cross-sectional analysis of the Joint Asia Diabetes Evaluation (JADE) program.

Background: In Asia, diabetes-associated death due to cardiorenal diseases were 2-3 times higher in women than men which might be due to gender disparity in quality of care and health habits.

Methods: Adults with type 2 diabetes (T2D) from 11 Asian countries/areas were assessed using the same protocol (2007-2015). We compared treatment target attainment (HbA < 7%, blood pressure [BP] < 130/80 mmHg, risk-based LDL-cholesterol, lack of central obesity [waist circumference <90 cm in men or <80 cm in women), use of cardiorenal-protective drugs (renin-angiotensin system [RAS] inhibitors, statins), and self-reported health habits including self-monitoring blood glucose (SMBG) by gender.

Ultrasound-guided dry needling versus traditional dry needling for patients with knee osteoarthritis: A double-blind randomized controlled trial.

Objective: To compare the effect of ultrasound (US)-guided dry needling (DN) with traditional DN in the treatment of pain and dysfunction for patients with knee osteoarthritis (KOA).

Design: A double-blind, randomized controlled trial.

Methods: Patients (25 male and 65 female), age 50-80 years diagnosed with KOA were recruited and randomly assigned to one of three groups in a 1:1:1 ratio for intervention: real US-guided DN with exercise therapy (G1), placebo US-guided DN with exercise therapy (G2), and exercise therapy solely (G3).

Attenuated Risk Association of End-Stage Kidney Disease with Metformin in Type 2 Diabetes with eGFR Categories 1-4.

Type 2 diabetes (T2D)-associated end-stage kidney disease (ESKD) is a global burden, while the renoprotective effects of metformin remain controversial. In a population-based cohort (2002-2018) including 96,643 patients with T2D observed for 0.7 million person-years, we estimated the risk association of metformin and its dose-relationship with ESKD in a propensity-score overlap-weighting (PS-OW) cohort by eGFR categories.

Combined associations of family history and self-management with age at diagnosis and cardiometabolic risk in 86,931 patients with type 2 diabetes: Joint Asia Diabetes Evaluation (JADE) Register from 11 countries.

Background: Family history (FamH) of type 2 diabetes might indicate shared genotypes, environments, and/or behaviors. We hypothesize that FamH interacts with unhealthy behaviors to increase the risk of early onset of diabetes and poor cardiometabolic control.

Methods: In a cross-sectional analysis of the prospective Joint Asia Diabetes Evaluation Register including patients from 427 clinics in 11 Asian countries/regions in 2007-2021, we defined positive FamH as affected parents/siblings and self-management as (1) healthy lifestyles (balanced diet, non-use of alcohol and tobacco, regular physical activity) and (2) regular self-monitoring of blood glucose (SMBG).

Multi-Omics-Based Autophagy-Related Untypical Subtypes in Patients with Cerebral Amyloid Pathology.

Recent multi-omics analyses paved the way for a comprehensive understanding of pathological processes. However, only few studies have explored Alzheimer's disease (AD) despite the possibility of biological subtypes within these patients. For this study, unsupervised classification of four datasets (genetics, miRNA transcriptomics, proteomics, and blood-based biomarkers) using Multi-Omics Factor Analysis+ (MOFA+), along with systems-biological approaches following various downstream analyses are performed.

Demographics and Medication Use of Patients with Late-Onset Alzheimer's Disease in Hong Kong.

Background: Alzheimer's disease (AD) is the most common cause of dementia in the elderly population. However, epidemiological studies on the demographics of AD in Hong Kong population are lacking.

Objective: We investigated the demographics, comorbidities, mortality rates, and medication use of patients with AD in Hong Kong to understand how the disease has been managed locally.

Effect of a Web-Based Management Guide on Risk Factors in Patients With Type 2 Diabetes and Diabetic Kidney Disease: A JADE Randomized Clinical Trial.

Importance: Diabetic kidney disease (DKD) and its comorbidities can be prevented by treating multiple targets. Technology-assisted team-based care with regular feedback and patient empowerment can improve the attainment of multiple targets and clinical outcomes in patients with type 2 diabetes, but the effects of this intervention on patients with DKD are unclear.

Objective: To evaluate the effect of the Joint Asia Diabetes Evaluation (JADE) web portal, nurse reminders, and team-based care on multiple risk factors in patients with DKD.

Association of SPI1 Haplotypes with Altered SPI1 Gene Expression and Alzheimer's Disease Risk.

Background: Genetic studies reveal that single-nucleotide polymorphisms (SNPs) of SPI1 are associated with Alzheimer's disease (AD), while their effects in the Chinese population remain unclear.

Objective: We aimed to examine the AD-association of SPI1 SNPs in the Chinese population and investigate the underlying mechanisms of these SNPs in modulating AD risk.

Methods: We conducted a genetic analysis of three SPI1 SNPs (i.

Rhynchophylline Administration Ameliorates Amyloid-β Pathology and Inflammation in an Alzheimer's Disease Transgenic Mouse Model.

Alzheimer's disease (AD), the most common neurodegenerative disease, has limited treatment options. As such, extensive studies have been conducted to identify novel therapeutic approaches. We previously reported that rhynchophylline (Rhy), a small molecule EphA4 inhibitor, rescues impaired hippocampal synaptic plasticity and cognitive dysfunctions in APP/PS1 mice, an AD transgenic mouse model.