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Gastric cancer (GC) is the fifth most diagnosed malignancy and the fifth leading cause of cancer-related deaths, with a poor overall survival of under one year. Metastatic tumors that arise from malignant primary tumors account for the majority of cancer-related deaths for GC. Hypoxia-inducible transcription factors (HIFs), including HIF-2α, and integrin such as ITGβ5 play important roles in tumor metastasis. However, the regulatory relationship and functional significance between HIF-2α and ITGβ5 in GC remain poorly understood. We analyzed TCGA RNA-seq data to identify hypoxia-related biological processes and signaling pathways in GC. Exosome proteomics was used to characterize the protein profiles of extracellular vesicles (EVs) derived from GC cells under hypoxia. Under hypoxic conditions, ITGβ5 expression in GC showed a positive correlation with HIF-2α levels. Clinical analysis confirmed the overexpression of ITGβ5, which was further validated by RT-qPCR, western blot, and flow cytometry. The chromatin immunoprecipitation (ChIP) was performed to confirm the binding of HIF-2α to the promoter of ITGβ5. The role of ITGβ5 in GC cell proliferation, invasion, and migration was investigated through gain- and loss-of-function studies conducted both in vivo and in vitro. Our results showed that HIF-2α directly binds to the promoter of ITGβ5, thereby transcriptionally activating its expression. In vivo and in vitro studies revealed that the overexpression of ITGβ5 significantly enhanced the invasion, migration, and growth of GC. Our study uncovers a novel pathway in which hypoxia-induced activation of HIF-2α promotes the proliferation, invasion, and metastasis of GC by directly upregulating the expression of exosomal ITGβ5. Given these findings, ITGβ5 may serve as a potential prognostic biomarker and therapeutic target for GC.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease driven by neutrophil dysregulation and neutrophil extracellular traps (NETs) formation, with unmet therapeutic needs. This study aimed to investigate the therapeutic potential of protein kinase CK2 inhibitor CX-4945 in SLE as well as to elucidate the underlying mechanisms. CX-4945 was administered to multiple murine models, including MRL/lpr mice, imiquimod (IMQ)-induced lupus model, IMQ-induced psoriasis model, and cecal ligation and puncture (CLP)-induced sepsis model. Renal function, histopathological changes, immune complex deposition, NETs formation, and inflammatory cytokine levels were evaluated. CX-4945 significantly ameliorated renal damage in MRL/lpr and IMQ-induced lupus models, as evidenced by reduced urinary albumin-to-creatinine ratio (ACR), glomerular abnormalities, immune complex/complement C3 deposition, and neutrophil infiltration. SLE patients' neutrophils exhibited elevated CK2α expression and enzyme activity. Mechanistically, CX-4945 suppressed interferon-stimulated genes (ISGs) and reactive oxygen species (ROS)-related pathways, induced mitochondrial metabolic rewiring, inhibited JNK/p38 MAPK phosphorylation, and modified NETs protein composition to abrogate macrophage proinflammatory responses. CK2α is aberrantly upregulated in SLE neutrophils, and targeting CK2 with CX-4945 exerts therapeutic effects in SLE. These findings identify CK2 as a novel therapeutic target for SLE and support the repurposing of CX-4945 for treating neutrophil-driven inflammatory and autoimmune diseases.

Vascular aging, characterized by progressive structural and functional deterioration of the vasculature, serves as a critical pathophysiological nexus between chronological aging and cardiovascular disease (CVD). This study establishes a quantitative vascular age model to decode individualized vascular senescence patterns, thereby enabling early identification of accelerated aging phenotypes for targeted intervention. We collected physical examination records from 2009 to 2019 and a total of 8578 participants aged 20-70 years were enrolled in this study. We constructed sex-specific basic vascular age models based on healthy individuals by Klemera-Doubal method and calculated the normalized cardiovascular age acceleration (NCAA, η) as an estimate of vascular aging status. The association between η and CVD risk were evaluated across subgroups. Furthermore, we developed expanded models by incorporating traditional CVD risk factors that were significantly associated with η index. Male with lower values of η, which meant relatively higher vascular aging velocity, had a higher risk of CVD adjusted by chronological age (HR = 1.21, 95% CI = 1.01-1.45). In subgroup analysis, η index exhibited age- and sex-specific associations with traditional CVD risk factors. After adding body mass index, fasting blood glucose, and triglycerides significantly related to η in male, the CVD prediction by expand η were improved in age-adjusted model (HR = 1.25, 95% CI = 1.04-1.50). The vascular age model emerges as a robust composite biomarker for CVD risk stratification. Our findings establish an evidence-based framework for precision prevention, prioritizing high-risk phenotypes for early intervention to mitigate CVD burden.

Advanced care planning (ACP) can reduce hospitalizations, increase quality of life, and align treatment with patient wishes, while lowering healthcare costs. However, healthcare providers' discomfort, lack of training, and patient anxiety may hinder ACP. Furthermore, disparities exist among minority and low-income groups. Growing research highlights the need for standardized definitions and broader implementation, especially post-COVID-19, incorporating digital tools, economic impacts, ethics, and family roles to improve ACP worldwide. This study aims to update and synthesize knowledge from all published systematic reviews from the past ten years, focusing on ACP-related interventions. We conducted a comprehensive search across PubMed, Cochrane, and Scopus, including only English-language, peer-reviewed systematic reviews published between 2015 and 2025. We employed rigorous screening, dual-reviewer validation, and quality-assessment tools, and synthesized evidence on intervention effectiveness across diverse populations and settings to identify effective ACP strategies. Of the deduplicated 7513 records, 61 reviews met the inclusion criteria. For older adult patients, structured conversations reduce unnecessary aggressive treatments and align end-of-life care with preferences. Among racial groups, peer support and palliative consultations boost ACP completion. Patient-centric interventions include video decision aids and web tools, whereas provider-centric interventions include conversation guides, reminder systems, electronic coordination platforms, and facilitator training. ACP is an ongoing process tailored to patient preferences, requiring efforts to address stigmatized conversations, especially in minority communities and severe illnesses. Emphasis on research into digital tools, policy incentives, infrastructure, and family support is essential. Bridging research and practice will improve outcomes and patient-centered end-of-life care. This article describes an umbrella review of 61 systematic reviews on advanced care planning-related interventions. The analysis indicates that the reviews covered interventions focusing on both facility and community-based individuals and had a specific population or disease focus. The articles covered both patient and provider-centric interventions.

Growing evidence supports the interdependence between oral health-related quality of life (OHRQoL) and formal social engagement (FSE) in later life. However, the causal direction of this relationship and potential gender differences therein remain underexplored. This study, informed by social causation and health selection perspectives within a social determinants of health framework, examines gender-specific patterns in the reciprocal relationship between OHRQoL and FSE among older adults in South Korea. A random-intercept cross-lagged panel model was applied to 3-wave panel data (2018, 2020, 2022) from 6,106 Korean adults aged ≥55 y. OHRQoL was assessed by the Geriatric Oral Health Assessment Index, validated for the Korean population. FSE was measured by the frequency of participation in structured organizational activities. The analysis identified significant bidirectional associations between OHRQoL and FSE at the within-person level, with distinct gender-specific patterns. Among men, better-than-usual OHRQoL predicted subsequent FSE, but the reverse path was not significant (health selection only). Among women, significant bidirectional associations were observed (social causation and health selection). These findings suggest gender-tailored interventions: alleviating oral health barriers to facilitate social reengagement for both genders, while leveraging social engagement to enhance OHRQoL specifically for women.

Heart failure (HF) is a major cause of morbidity and mortality worldwide and is frequently associated with dysfunction of other organs, including the liver. Hepatic congestion and impaired perfusion from cardiac dysfunction may lead to liver injury, described as cardiohepatic syndrome. Studies suggest that liver dysfunction markers, such as the Model for End-Stage Liver Disease (MELD) and MELD excluding international normalized ratio (MELD-XI) scores, may serve as prognostic indicators in HF patients. This systematic review and meta-analysis evaluated the relationship between liver dysfunction markers and mortality outcomes in HF patients. A systematic literature search was conducted. Studies evaluating the association between liver dysfunction markers (MELD or MELD-XI scores) and mortality outcomes in adult HF patients were included. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using the generic inverse variance method with a random-effects model in Review Manager (RevMan) version 5.4 (The Cochrane Collaboration, Copenhagen, Denmark). Subgroup analyses were performed by liver dysfunction marker type and HF phenotype. The primary outcome was all-cause mortality. Nine studies comprising over 32,000 HF patients were included. Elevated liver dysfunction markers were significantly associated with increased mortality risk (pooled HR = 1.12, 95% CI 1.06-1.18). Substantial heterogeneity was observed (I² = 91%). Subgroup analysis showed significant associations for both MELD-XI (HR = 1.09, 95% CI 1.04-1.14) and MELD scores (HR = 1.10, 95% CI 1.06-1.14). Analysis by HF type revealed significant associations in acute HF (HR = 1.07), chronic HF (HR = 1.23), and advanced HF (HR = 1.05). Sensitivity analyses confirmed the findings, with no substantial publication bias observed. Elevated liver dysfunction markers significantly correlate with increased mortality in HF patients. Both MELD and MELD-XI scores provide prognostic information across HF populations. These findings emphasize the importance of considering hepatic dysfunction in HF assessment and suggest liver dysfunction markers may aid risk stratification. Further prospective studies are needed to determine the role of these markers in clinical decision-making.

Concerns about hypotension and excessive blood pressure (BP) variability leading to falls may be a barrier to achieving BP treatment goals among older adults. Home BP monitoring (HBPM) may allow for better BP management while avoiding falls. Participants, aged ≥65 years taking antihypertensive medication (n = 541), were instructed in proper HBPM technique and asked to take 2 morning and 2 evening readings for 7 days. Among 499 participants with ≥4 days of HBPM, white coat effect was defined as mean clinic BP minus mean BP on HBPM. Day-to-day variability was calculated using standard deviation independent of the mean (SDIM). Participants reported falls monthly for 1 year. We estimated hazard ratios (HRs) for falls across quartiles of systolic BP on HBPM, white coat effect and SDIM, separately, adjusting for demographic characteristics and chronic conditions. The mean ± SD age of participants was 74.2 ± 6.1 years, and 57.3% were women. Prefrailty and frailty prevalence were 50.7% and 3.4%, respectively. Participants in the highest versus lowest quartile of mean SBP from HBPM were older and more frequently male. Over 379 person-years, 187 participants reported falls. Comparing the highest and lowest quartiles, the HRs (95% confidence interval) were 0.85 (0.53-1.37), 0.84 (0.51-1.40), and 0.97 (0.62-1.51) for mean systolic BP, white coat effect, and SDIM, respectively. There was no evidence of associations between these measures for diastolic BP and falls. BP measured using HBPM was not associated with falls among older US adults with treated hypertension.

To investigate treatment variations and outcomes between older (&#x2265;&#x2009;70&#x2009;years) and younger (<&#x2009;70&#x2009;years) patients with mucosal head and neck squamous cell carcinoma (mHNSCC) treated with radiotherapy. A multicenter retrospective review of patients diagnosed from 2010 to 2018 was conducted. Patient, tumor, and treatment data were collected, including overall survival (OS) and progression-free survival (PFS). Multivariable analyses examined factors influencing standard-of-care (SOC) treatment, OS, and PFS. Of 1553 patients, 432 patients were &#x2265;&#x2009;70&#x2009;years. Older patients were significantly less likely to receive curative treatment, SOC, or concurrent systemic therapy. Age, marital status, ECOG status, stage, and subsite influenced SOC treatment. Three-year OS and PFS were lower in older patients. ECOG status, stage, subsite, and SOC treatment were significantly associated with OS and PFS. Older age and smoking status were significantly associated with lower OS but not PFS. Older patients should be offered SOC treatment where appropriate for maximal disease control and survival.

Adult spinal deformity (ASD) significantly impacts quality of life in geriatric populations due to severe sagittal imbalance, degenerative scoliosis, and associated neurological compression that usually requires surgery when conservative treatment fails. To evaluate the clinical and radiological outcome of a modified transforaminal lumbar interbody fusion (TLIF) technique in the three-planar correction of severe adult spinal deformity (ASD). This was a single-center case series study. We recruited 72 ASD patients (mean age 64.5 years) with at least one of the following criteria met (SRS-Schwab sagittal modifier ++; Cobb angle >30&#xb0;; Coronal vertical axis >3cm) operated between January 2020 and May 2025. The surgical protocol involved four modifications: (1) bilateral facetectomy and posterior column resection; (2) a concave-side approach to the disc space; (3) anterior positioning of the PEEK cage; and (4) supplemental bone grafting posterior to the cage. Clinical and radiological outcomes were evaluated at a mean follow-up of 2.3 years. Significant improvements were observed in SRS-22 (2.6 to 3.7) and NCOS (43 to 74.5) scores (p < 0.05). After surgery, both PI-LL mismatch and the Cobb angle have been markedly improved (35&#xb0; down to 17&#xb0; and 21.5&#xb0; down to 5&#xb0;, respectively). The fusion rate was 90% at 1 year. Univariate analysis identified osteoporosis (OR = 13.4, p<0.05), "pear-shaped" disc morphology (OR = 14, p<0.05), and PI > 65&#xb0; (OR = 13.7, p<0.05) as significant risk factors for unchanged sagittal modifier after surgery. Early complications included infection (2.7%) and pneumonia (2.7%) whereas the main mid-term adverse event was PJK (15%). Modified TLIF is associated with improvement of mid-term radiographic and clinical outcomes and an acceptable complication rate. Additional research involving larger cohorts and extended follow-up, preferably with a control group, is required to reach more definitive conclusions.

This study aimed to evaluate hand hygiene compliance among healthcare workers of different roles, identify key barriers using the Consolidated Framework for Implementation Research (CFIR), and assess the effectiveness of a CFIR-guided stratified intervention in a tertiary hospital. An exploratory sequential mixed-methods study was conducted at Beijing Hospital, National Center of Gerontology, from December 2024 to September 2025. The observational phase included 9,767 non-announced direct observation hand hygiene observations and a survey of 275 staff (71 physicians, 173 nurses, 31 support staff), supplemented by 15 semi-structured interviews. A six-month CFIR-guided intervention was then implemented, incorporating role-specific training sessions, data-driven feedback, visual reminders, and position-based supervision tailored to physicians, nurses, and support staff. Outcomes included hand hygiene compliance and correctness, knowledge scores, and hospital-acquired infection (HAI) rates. At baseline, compliance differed by role: nurses 81.6%, physicians 72.6%, and support staff 39.3% (p < 0.001). Knowledge scores were significantly lower among support staff (58.6 &#xb1; 9.4) than physicians and nurses (66.1 &#xb1; 6.9, p < 0.001). Qualitative interviews and CFIR-based surveys identified barriers including workflow constraints, insufficient supervision, inadequate training coverage, and knowledge gaps. Following the intervention, overall compliance increased from 74.9 to 85.4% (p < 0.001), with the largest improvement among support staff (39.3% vs. 56.0%, p = 0.002). Compliance improved across all "five moments," particularly before patient contact (+18.5%, p < 0.001). HAI rates were lower from 3.05 per 1,000 patient-days to 1.66 per 1,000 patient-days (p = 0.002), with reductions observed in respiratory, urinary tract, bloodstream, and surgical site infections during the study period. Hand hygiene compliance varies substantially across healthcare worker roles, with support staff representing a critical gap. A CFIR-guided, stratified intervention was associated with increases in compliance and correctness, particularly at high-risk moments, and reduced HAI incidence, suggesting its potential value as a sustainable framework for hospital-wide infection prevention.

Although peripheral artery disease (PAD) is an important diabetes complication, a substantial proportion of cases occur among individuals without diabetes. This study aimed to assess the predictive value of plasma proteomics in the long-term risk of PAD among individuals initially free of diabetes. Included were 46&#x2009;508 participants (6046 with prediabetes) without diabetes or major cardiovascular disease at recruitment of the UK Biobank. Using multivariable Cox regression models, a total of 2923 unique plasma proteins were assessed for the associations with incident PAD. Significant proteins were subsequently processed by a trained light gradient boosting machine classifier to determine important proteins. Using receiver operating characteristic analyses, the performance of these important proteins in predicting incident PAD were evaluated, in the whole sample and by glycemic status (normoglycemia and prediabetes). During a median follow-up of 12.7&#x2009;years, 461 participants developed PAD. There were 107 proteins associated with incident PAD, with 103 positive associations. The LGBM approach identified 9 proteins (eg, WFDC2 [WAP 4-disulfide core domain protein 2], MMP12 [macrophage metalloelastase], and GDF15 [growth differentiation factor 15]) as the top-ranked proteins based on their importance ordering. Whereas glycated hemoglobin showed very modest predictive accuracy, a panel incorporating these top proteins showed good performance in the prediction of PAD risk (area under the curve 0.820), and it significantly enhanced the prediction beyond traditional risk factors (raising area under the curve from 0.803 to 0.837, DeLong test P=5.21&#xd7;10-3). These observations were consistent for participants with normoglycemia or prediabetes. Plasma protein biomarkers enhance the prediction of long-term risk for PAD among individuals without diabetes, regardless of glycemic status.

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The host immune determinants that distinguish protective from life-threatening responses to influenza are poorly understood. Identifying drivers of immunopathology in the human lung is critical for developing potential therapies. To define the cellular and molecular immune landscape of the lung in mild versus severe influenza and to identify key cellular states and pathways associated with disease severity. We generated a large-scale single-cell atlas by sequencing over 520,000 cells from the bronchoalveolar lavage fluid of 88 non-immunocompromised adult individuals with mild or severe influenza A and healthy controls. Key findings were validated by flow cytometry and protein quantification, and machine-learning models were used to identify predictive signatures. Severe influenza was characterized by profound pulmonary lymphopenia and a massive influx of functionally dysregulated neutrophils. The infiltrating neutrophils were primed for extracellular trap formation, driving a cytokine storm via the S100A8/A9/A12-TLR4 and CXCL8-CXCR1/2 axes. This pathology coincided with the depletion and functional impairment of resident alveolar macrophages and an expansion of pro-inflammatory, monocyte-derived macrophages that amplified neutrophil recruitment. Lymphopenia in severe disease arose from synergistic cell-death programs, while remaining lymphocytes exhibited a dysfunctional state of concurrent exhaustion and hyper-cytotoxicity. Mild influenza featured a coordinated adaptive immune response, distinguished by an enrichment of T follicular helper cells and plasma cells. Machine-earning models identified robust cellular and transcriptional signatures predictive of disease severity. Our atlas defines the divergent immune trajectories in influenza, revealing specific cellular states and pathways that drive immunopathology and provide novel targets for host-directed therapies.

ObjectivesThis study aimed to examine the clinical progression of Stage 2, 3, and 4 pressure ulcers (PUs) in patients receiving palliative care, and to assess the psychosocial burden and burnout levels among their primary caregivers. Additionally, it sought to identify patient- and caregiver-related factors that may influence short-term mortality.MethodsA total of 96 patients with advanced-stage PUs and their 96 primary caregivers were included in a study. The Pressure Ulcer Scale for Healing (PUSH) was used to evaluate wound severity at baseline and at a 3-month follow-up. Caregiver burden and burnout were assessed using the Zarit Burden Interview and Maslach Burnout Inventory. Sociodemographic data were also collected. Logistic regression analysis was performed to determine predictors of mortality.ResultsAt the end of the 3-month follow-up, 35 patients (36.5%) survived, showing statistically significant improvement in PUSH scores (p&#x2009;<&#x2009;.05). Patient age was positively correlated with mortality. Additionally, a significant inverse relationship was found between caregiver "personal accomplishment" scores and patient mortality (p&#x2009;<&#x2009;.05), suggesting that caregivers with lower perceived competence were associated with higher patient death rates.ConclusionPUs in palliative care are associated with high mortality and complex care demands. The results emphasize the importance of caregiver psychological well-being in influencing patient outcomes. Multidisciplinary strategies that include both clinical wound management and structured psychosocial support for caregivers are essential to improve the quality of care and survival among this vulnerable population.

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Frailty is a prevalent geriatric syndrome linked to adverse health outcomes, yet optimal intervention strategies remain limited. Virtual Reality (VR), a technology that enables subjects to immerse themselves in a computer-generated environment, is increasingly used in clinical nursing. Virtual reality has demonstrated both theoretical and practical benefits in mitigating physical, cognitive, and functional impairments among frail older adults; however, its overall efficacy remains to be systematically synthesized. This study aimed to evaluate the specific effects of VR-based training on frailty in elderly patients. A comprehensive search of one clinical trial registry and nine Databases including China National Knowledge Infrastructure (CNKI), Wanfang, VIP, Chinese Biomedical Literature Service System, PubMed, Web of Science, CINAHL, Cochrane Library, and Embase was conducted up to 30 May 2025. Randomized controlled trials (RCTs) of virtual reality-based training for frail elderly individuals aged&#x2009;&#x2265;&#x2009;60 years with normal mobility and no cognitive impairment, were included. Data extraction and quality assessment were conducted independently by 2 reviewers. All Statistical analyses were conducted using a random effects model in RevMan 5.4. A total of 9 RCTs involving 634 patients were screened, and risk of bias was assessed across all included studies using the Cochrane risk-of-bias tool version 2 (ROB2). Our results indicate that VR-based training group can fluence frailty severity as measured by the Fried Frailty Phenotype (FFP) scale [MD&#x2009;=&#x2009;-&#x2009;0.33, 95%CI (-&#x2009;0.54, -&#x2009;0.12), P&#x2009;&#x2009;=&#x2009;0.002], fear of falling [MD&#x2009;=&#x2009;-&#x2009;1.34, 95%CI (-&#x2009;3.08,0.39), P&#x2009;=&#x2009;0.13], static balance (One-Leg Stand Test duration and Functional Reach Test distance) (P&#x2009;<&#x2009;0.05), dynamic balance as measured by the Berg Balance Scale [MD&#x2009;=&#x2009;1.17, 95%CI (-&#x2009;1.41,3.75), P&#x2009;=&#x2009;0.37], Timed Up and Go test [MD&#x2009;=&#x2009;-&#x2009;0.19, 95%CI (-&#x2009;0.80,0.42), P&#x2009;=&#x2009;0.54], and Mini-BESTest [MD&#x2009;=&#x2009;-&#x2009;0.70, 95%CI (-&#x2009;1.62,0.22), P&#x2009;=&#x2009;0.13], gait speed [SMD&#x2009;=&#x2009;-&#x2009;0.17, 95%CI (-&#x2009;0.56,0.22), P&#x2009;=&#x2009;0.39], handgrip strength [SMD&#x2009;=&#x2009;0.02, 95%CI (-&#x2009;0.21,0.24), P&#x2009;=&#x2009;0.89], lower limb strength as measured by the Five-Times Sit-to-Stand Test [SMD&#x2009;=&#x2009;-&#x2009;0.24, 95%CI (-&#x2009;2.50,2.03), P&#x2009;=&#x2009;0.84], 30-Second Chair Stand Test repetitions (P&#x2009;<&#x2009;0.05) and Global cognitive function [MD&#x2009;=&#x2009;0.63, 95%CI (-&#x2009;0.11,1.37), P&#x2009;=&#x2009;0.09]. VR-based training is effective in improving frailty status, static balance, and lower limb strength in elderly patients with frailty, considering as a promising nursing strategy.

Atrial fibrillation (AF) is a major contributor to ischemic stroke, with risk influenced by age and comorbidities. Age is the strongest risk factor and appears to also modify others, such as vascular disease and female sex. However, data on its impact on additional key risk factors remain limited. We conducted a nationwide retrospective cohort study to examine whether the association between heart failure (HF) and ischemic stroke in patients with AF is age dependent. The FinACAF (Finnish Anticoagulation in Atrial Fibrillation) study includes all patients with AF in Finland from 2007 to 2018. Data were collected from healthcare registries encompassing all levels of care. Incidence rate ratios for stroke were calculated comparing patients with HF to those without HF across the entire age spectrum. We identified 229&#x2009;565 patients with new-onset AF. The prevalence of HF was higher among older patients compared with younger patients (38.7% versus 4.3%, respectively). The association between HF and ischemic stroke was highest among younger patients (incidence rate ratio, &#x2265;2.0 for those aged <60&#x2009;years) and gradually diminished with advancing age, approaching an incidence rate ratio of &#x2248;1.0 in the oldest group (P<0.001, for interaction between age and incidence rate ratio). The adjusted absolute rate difference between patients with and without HF remained stable, at &#x2248;1 event per 100 patient-years, across all age categories. HF was more strongly associated with ischemic stroke in younger patients than in older individuals with AF, highlighting the importance of considering HF in the decision making about oral anticoagulation, particularly in younger patients.

Elevated low-density lipoprotein cholesterol is one of the major modifiable risk factors for cardiovascular disease. Lipid management is integral to primary and secondary prevention of cardiovascular disease, but undermined by high prevalence of non-adherence to lipid-lowering medications. Innovative, personalized multicomponent interventions may address the gaps in medication non-adherence. We aim to evaluate the effectiveness of a human coach-supported digital personal health assistant (mobile health app) intervention in improving adherence to statins in adults with hyperlipidaemia. AdLip is a multicentre, open-label, parallel, two-arms, randomized controlled trial aiming to recruit a minimum of 376 adult participants who are non-adherent to statins from primary care ambulatory clinic setting in Singapore. Participants recruited will be randomly assigned (1:1) to human-coach supported mobile health app intervention or control group. The primary outcome will be adherence to statins at 6 months, measured by Medication Adherence Report Scale-5. Secondary outcomes will include change in serum low-density lipoprotein cholesterol levels, health motivation and attitudes, self-efficacy, self-care behaviours, quality of life, app acceptability, user engagement, and cost-effectiveness. Outcomes will be analysed using intention-to-treat approach. The AdLip trial will provide empirical evidence on a multicomponent approach to the long-standing challenge of suboptimal adherence to statins in a multi-ethnic Asian setting. Findings from this study may inform a more personalized approach to addressing non-adherence in the short term, and how it relates to cardiovascular disease prevention in the longer term. Trial Registration: ClinicalTrials.gov NCT06614049.

Dementia poses a significant public health challenge. Early detection is crucial for timely intervention but remains difficult in community settings, as many existing cognitive screening tools are either insufficiently sensitive to subtle decline or too burdensome for widespread use. This study aimed to develop and validate a novel combined audiovisual-semantic digital tool for rapid and acceptable community-based screening of cognitive decline in older adults. A total of 156 older adults completed 6 progressively complex task variants shifting from unimodal to multimodal stimuli and from basic to superordinate semantic categorization. Performance was measured using reaction time, accuracy, false alarms, and inverse efficiency. Diagnostic utility was assessed via logistic regression and receiver operating characteristic curve analysis, whereas qualitative interviews evaluated acceptability. Task outcomes showed significant declines across the cognitive continuum from no cognitive impairment to mild cognitive impairment to dementia (P<.001). The integrated audiovisual-semantic condition at the basic categorization level reliably differentiated cognitive groups and achieved higher area under the curve values for distinguishing no cognitive impairment from cognitive impairment and mild cognitive impairment from dementia compared to basic-level tasks. Incorporating semantic processing enhanced diagnostic discrimination. Participant feedback was highly positive, with 48.7% (76/156) describing the tasks as "fun/interesting." The audiovisual-semantic integrated digital tool is a valid, well-accepted, and time-efficient instrument for cognitive screening in older adults. Its design, which increases cognitive load through multimodal and semantic integration, improves sensitivity to early decline, supporting its potential for practical community application.