To evaluate the correlation between novel metabolic and inflammatory-derived Indicators (TyG, THR, NHR, UHR) for overweight in older adult type 2 diabetes mellitus (T2DM) patients. This study enrolled 183 hospitalized older adult T2DM patients (aged ≥ 60 years) from 2023 to 2024. Participants were stratified into overweight (24 ≤ BMI < 28, n = 85) and normal-weight groups (18.5 ≤ BMI < 24, n = 98). Clinical parameters including TyG, THR, NHR, and UHR were calculated. Statistical analyses involved t-tests, logistic regression, Spearman correlation, and ROC curves. Key metabolic/inflammatory derived indices (TyG, THR, NHR, UHR) were significantly elevated in overweight group versus normal group (all P < 0.05). BMI showed positive correlations with TyG, THR, NHR, and UHR (all P < 0.05). Logistic regression confirmed the TyG, THR, NHR and UHR index are significantly associated with the development of overweight in T2DM patients (all P < 0.05). After adjusting for confounders, TyG demonstrated the highest predictive accuracy for overweight status (AUC = 0.732), followed by THR, NHR and UHR. TyG, THR, NHR and UHR are significantly associated with overweight in older adult T2DM, potentially serving as simple screening tools for early metabolic risk stratification and weight management.

IntroductionThis study evaluated 6-month effectiveness and safety of automated insulin delivery (AID) in comparison with multiple daily injections (MDI) in pediatric and adult type 1 diabetes (T1D).Materials and methodsIndividuals with T1D, aged 2–80 years, were enrolled across 32 international centers (in the United States, Europe, Canada, and New Zealand) and randomized 1:1 to AID intervention (MiniMed™ 670G or 770G system) or MDI with or without continuous glucose monitoring. Primary endpoints were change in mean HbA1c for participants with a baseline HbA1c >8.0% (Group 1) and percentage of time spent below 70 mg/dL (%TBR <70 mg/dL [<3.9 mmol/L]) for participants with baseline HbA1c ≤8.0% (Group 2), to show superiority of AID intervention versus MDI. Safety endpoints including rates of severe hypoglycemia and diabetic ketoacidosis (DKA), and difference in diabetes treatment satisfaction score were assessed.ResultsFor Group 1, N = 56 participants (aged 29.4 ± 17.0 years) were randomized to AID intervention and N = 54 participants (aged 36.8 ± 19.6 years) were randomized to MDI. For Group 2, N = 73 (aged 37.4 ± 21.0 years) and N = 69 (aged 39.2 ± 19.3 years), respectively, were randomized to AID and MDI. Change in HbA1c (mean [95% CI] difference of −0.7% [−1.1, −0.3], P = 0.0002) and difference in %TBR <70 mg/dL (4.8% [−6.4, −3.1], P<0.001) favored AID intervention versus MDI. Rates of severe hypoglycemia (AID: 1.82/100 patient-years) and DKA (MDI: 3.52/100 patient-years) were low and met preestablished success criteria for safety.DiscussionThis large, international, multicenter randomized controlled trial demonstrates safety of the MiniMed™ 670G/770G systems. AID significantly improved HbA1c and time spent in hypoglycemia when compared with MDI, in both youth and adults living with T1D.Clinical trial registrationhttps://clinicaltrials.gov/, identifier NCT02748018.

This study aimed to determine whether cigarette dependence is an independent risk factor for new-onset proliferative diabetic retinopathy (PDR) and related neovascular complications in patients with type 2 diabetes mellitus (DM) and to assess the impact of smoking cessation. A retrospective cohort analysis using a clinical database was conducted with adult type 2 DM patients, excluding those with conditions affecting PDR progression. Propensity score matching was used to balance demographic and clinical factors between cigarette-dependent patients and controls. After matching, cigarette dependence was seen to significantly increase the risk of first-instance PDR (hazard ratio [HR] 1.195), vitreous hemorrhage (HR 1.450), neovascular glaucoma (HR 1.469), and tractional retinal detachment (HR 1.670). Smoking cessation attempts reduced these risks (HR 0.716 for PDR, 0.722 for complications). Cigarette dependence increases the risk of PDR and its complications in type 2 DM, and smoking cessation reduces these risks.

Diabetic kidney disease (DKD) and diabetic nephropathy (DN) affect around 40% of diabetic patients but lack accurate risk prediction tools that include social determinants and demographic complexity. We developed and validated an ensemble machine learning model for three-year DKD/DN risk prediction with deployment readiness. We analysed 18 742 eligible adult type 2 diabetic patients from Prince Sultan Military Medical City (PSMMC) registry between 2019 and 2024 in Riyadh, Saudi Arabia. Using temporal patient-level splitting, we developed a stacked ensemble model (LightGBM + CoxBoost) with several features including multiple literature-informed imputed variables including family history, non-steroidal anti-inflammatory drug (NSAID) use, socioeconomic deprivation, diabetic retinopathy severity, and antihypertensive medications, imputed via Bayesian multiple imputation by chained equations (MICE) with external study priors. Primary outcome was incident/progressive DKD/DN within 3 years' timeframe. We assessed discrimination, calibration, model utilisation, and algorithmic fairness. The final model achieved excellent discrimination (receiver operating characteristic [AUROC] of 0.852, 95% CI 0.847-0.857) and near-perfect calibration (slope 0.98, intercept -0.012) on multi-trial validation. Decision curve evaluation demonstrated superior net benefit (+22 events prevented per 1000 patients at 10% threshold) compared to treat-all strategies. Bootstrap validation showed minimal optimism in discrimination (C-statistic optimism = 0.005). No algorithmic bias was detected across demographic subgroups (maximum |Δ-AUROC| = 0.010). Prior sensitivity analysis confirmed validity and significance (AUROC variation ≤0.008). The model was engineered and deployed as an interactive web-based application (https://nephrarisk.streamlit.app/). Our developed and demonstrated model provided accurate and well-fair DKD/DN risk prediction with excellent calibration, allowing for better decision making with deployment as a web-based research tool and framework for future prospective clinical validation. Further validation and testing are warranted from different centres and healthcare systems to increase confidence and dissemination of our model findings for better utilisation purposes in the future.

With the deepening trend of population aging and the increasing diversification of elderly care models, enhancing the well-being of older adults has become a central focus in both research and practice within the social care sector, building upon the foundation of ensuring their material livelihood and spiritual experience. This paper systematically analyzes the core healthy elderly care needs of different types of older adults, constructs a multi-level integrated medical and elderly care service system, and optimizes the multi-level, multi-format community-based care service model from the perspective of well-being enhancement. This research not only contributes to the systematization and standardization of elderly care services but also holds significant importance for driving the development of related industries, absorbing more social employment, and further implementing the national strategy for actively addressing population aging.

Telehealth Use by Residence Type in Older Adults Receiving Long-Term Services and Supports: The US National Core Indicators Survey (2021-2022).

Processing speech that is non-canonical (i.e., child-produced speech) and/or presented in background noise can pose challenges for listeners. We investigated how listening to child-produced speech affects young adults' word recognition under varying noise conditions. Participants (n = 121) completed a two-picture eye-tracking task in one of three conditions: no background noise, pink background noise, and real-world background noise from LENA recordings. Participants heard a child or adult (Speaker-Age) direct attention to a generic (e.g., keys) or child-specific (e.g., potty; Item-Type) item. We examined the effect of Speaker-Age and Item-Type on participants' looking time. In no background noise, increases in target looking were high, with greater increases when adults produced generic items. Both pink noise and real-world noise increased task difficulty, but patterns of results varied as a function of speaker gender. For female speech, background noise resulted in an effect of Speaker-Age, with participants increasing their looking time more for adult relative to child speech. The type of background noise did not influence this pattern. For male speech, there was an effect of Speaker-Age in the opposite direction, with participants increasing their looking time more for child relative to adult speech. For male speech, real-world background noise resulted in higher increases in target looking for child-specific items. Together, results suggest that child-produced speech may be more difficult to process than female-adult produced speech in noise, and that listeners can use background noise to predict who will speak and what they might speak about under more challenging conditions, such as processing male speech.

Cardio-renal Outcomes in Type 2 Diabetes Patients with Advanced Chronic Kidney Disease on SGLT2 inhibitors or GLP-1 receptor agonists.

Should we talk about bodies? Examining the associations between different types of body talk and older adults' eating disorder pathology through the lens of growth mindset.

BackgroundA key feature of tauopathies, including Alzheimer's Disease (AD), is progressive deterioration of neuronal subsets within specific brain regions. One explanation for regional preference is selective vulnerability of different neurons to pathogenic proteins. To date, animal models have examined pathogenic protein expression in broad or heterogeneous neuronal populations, meaning noted pathological hallmarks represent an average of disease phenotypes over many neuron types. Our solution is a genetic toolset for targeting gene expression to single neuron types in the Drosophila central nervous system (CNS), allowing us to analyse disease pathogenesis and progression over lifespan at sub‐cellular resolution.MethodUsing this toolset, we analysed the vulnerability of adult neuron types in the Drosophila CNS to the toxicity of the highly‐phosphorylated human tau isoform, hTau0N3R. We examined the effects of tau on cell morphology, pathological tau phosphorylation (AT8), and trafficking (vesicles and mitochondria).ResultOur model recapitulated typical age‐dependent tau phenotypes shown in many studies (e.g., loss of synaptic terminals, tau mislocalisation, beading/blebbing of neuronal processes). While all neurons examined were affected by tau, some were more vulnerable than others. The tau‐mediated pathogenic effects fell on a spectrum demonstrating that fly neurons are differentially vulnerable to tau pathology. Mechanistically, total tau levels did not correlate with vulnerability; rather, degeneration correlated with significant age‐dependent increases in phospho‐tau levels in the same neuron type, and tau mislocalisation into dendrites. Lastly, increased p‐tau levels correlated with downstream vesicular and mitochondrial trafficking defects in some neurons but not all.ConclusionThis work highlights the heterogeneity of responses underpinning neuronal vulnerability to tau. Thus, innate cellular factors play an essential role in determined vulnerability. Further, this work provides a new model for studying AD with sub‐cellular resolution. Current ongoing work aims to examine the role of individual tau isoforms on selective vulnerability.

BackgroundMicroglial cells are critical in Alzheimer’s disease (AD) pathophysiology. Most human studies have analyzed microglia from postmortem brain samples or microglia derived from induced‐pluripotent stem cells. Our study provides evidence to support human monocyte‐derived microglia‐like cells as a cellular model to identify potential biological markers of mild cognitive impairment (MCI).MethodPeripheral blood monocytes were isolated from cognitively healthy volunteers (n =13, age 50‐75 years old), patients with MCI (n =4, age 58‐75 years old), and one patient with possible AD (77 years old). Monocytes were cultured with IL‐34 and GM‐CSF for 14 days to induce the microglial‐like phenotype, which was verified through flow cytometry and immunofluorescence. Total RNA from monocytes and microglia‐like cells was extracted and processed for RNASeq.ResultFrom a total of 19549 genes with measured expression, 4648 genes were differentially expressed (DE) in microglia‐like cells (p ‐value 0.05; log fold change 2.2). After Bonferroni correction, 26 biological pathways (KEGG), 256 biological processes, 47 cellular components, and 50 molecular functions (Gene Ontology: GO) were significantly impacted. 92% of DE genes from 7 types of monocytes were significantly downregulated, while 54% of DE genes from 3 adult microglial types were significantly upregulated. SPP1, APOE, and TREM2 genes, all three considered AD‐associated genes expressed in brain microglia, were among the top 30 DE genes. When samples from MCI patients were compared with those of cognitively healthy subjects, 262 DE genes were identified, two biological pathways were impacted, and 139 GO‐terms were significantly enriched.ConclusionThe transcriptomic profile of human monocyte‐derived microglia‐like cells suggests that this cellular model might be suitable for multi‐omic analysis to identify potential biological markers of mild cognitive impairment and AD.

Prenatal superficial musculoaponeurotic system anlage.

Purpose: This study investigated differences in the use of life-sustaining treatments during the last six months of life between older adults covered by the National Health Insurance (NHI) and those enrolled in the Medical Aid (MA) program. Methods: A retrospective cohort design was applied using national claims data from the National Health Insurance Service. The study population included individuals aged ≥65 years who died in 2023, with 286,319 decedents (247,935 with NHI and 38,384 with MA) analyzed. We compared hospitalization frequency and duration, intensive care unit (ICU) stays, and the use of life-sustaining treatments, including cardiopulmonary resuscitation, mechanical ventilation, hemodialysis, chemotherapy, transfusions, and vasopressors, between NHI and MA groups. Logistic regression analyses were conducted with adjustments for age, sex, comorbidities, place of death, and advance care planning status. Results: Completion rates of advance directives and physician orders for life-sustaining treatment were lower in MA than in NHI decedents. MA decedents had fewer admissions but significantly longer hospital and ICU stays than NHI decedents. They were less likely to receive mechanical ventilation, chemotherapy, transfusion, and vasopressors but more likely to undergo hemodialysis. Conclusion: Substantial disparities exist in end-of-life care by insurance type, suggesting that socioeconomic inequalities and reimbursement structures influence patterns of intensive care near the end of life. Targeted interventions are needed to ensure equitable, patient-centered end-of-life care for socioeconomically vulnerable older adults.

IntroductionThe neutrophil lymphocyte ratio (NLR) is a readily accessible marker of systemic inflammation. This study evaluated the association between NLR with all-cause mortality, major adverse vascular events and diabetic kidney disease (DKD) progression in a multiethnic cohort of adult type 2 diabetes mellitus (T2DM) individuals in Singapore.MethodsDemographic, anthropometric, biochemistry, mortality and major adverse vascular events (MAVE) were obtained from electronic medical records up to June 30, 2024. Composite renal outcomes were defined as one of the following: decline in eGFR ≥ 40%, decline in eGFR to ≤ 15ml/min/1.73m2 or initiated maintenance dialysis. Multivariate Cox regression analyses were performed to evaluate associations between NLR, all-cause mortality, MAVE and composite renal outcomes.ResultsIn this cohort of 959 adult participants with T2DM, there was a significant association between NLR with all-cause mortality, MAVE, baseline albuminuria, renal function and progression of DKD. During the median follow-up of 9.4 years, there were 367 (38.3%) mortalities, 222 (23.1%) cases of MAVE and 285 (30%) participants who developed a renal outcome. The highest NLR was associated with a 1.6-fold increased risk for all-cause mortality (HR 1.63; 95% 1.18 - 2.27, p=0.003), 2.7-fold increased risk of MAVE (HR 2.71; 95% CI 1.75 - 4.20; p<0.001) and 1.55 (HR 1.55, 95% CI 1.09 - 2.19, p=0.014) increased risk of having a renal event compared to the lowest NLR tertile after adjusting for confounders.ConclusionElevated NLR is independently associated with all-cause mortality, MAVE and composite renal outcomes in T2DM. NLR may be considered a potential clinical biomarker of adverse outcomes for use in routine care.

Gene expression can be used to define prognostic and predictive biomarkers across cancers and treatment modalities. PRECOG (https://precog.stanford.edu) is a compendium of datasets with gene expression and clinical outcomes that facilitates visualization of associations between genomic profiles and patient survival. Here, we augment the existing PRECOG with over 10 000 new patients in previously poorly represented adult cancer types, as well as adding annotated pediatric and immunotherapy treated cohorts. Pediatric PRECOG comprises over 3000 patients across 12 cancers; while the checkpoint inhibitor (ICI) PRECOG contains over 4000 patients across 20 cancer subtypes from 80 distinct datasets across 51 studies. Together this represents a doubling in the size of the PRECOG database. We compute and visualize associations of gene expression with survival outcomes using Cox regression for time-to-event, or logistic regression for responder versus nonresponder, across all datasets. We also estimate cell type fractions in samples via computational deconvolution using CIBERSORTx, to identify survival associations at the level of cell types. All expression data, clinical annotations, and gene and cell type survival z-scores and meta-z scores for adult, pediatric, and ICI PRECOG, are available for interactive analysis and download, along with Kaplan-Meier and boxplot visualizations. This updated resource will provide new insights into biomarkers for specific therapies, populations, and cancer types.

Shank3 establishes AMPA receptor subunit composition at cerebellar mossy fiber-granule cell synapses and is associated with altered regional microglial morphology

The potential impact of heavy metal exposure on the progression of diabetic kidney disease (DKD) remains a subject of scientific inquiry. While some studies have hinted at a correlation, definitive evidence is still lacking. It is important to note that certain links, such as the association between cadmium exposure and chronic kidney disease, have been established in prior research. This study seeks to examine the potential link between heavy metal exposure and the risk of DKD. This cross-sectional study included adult type 2 diabetes mellitus (T2DM) patients from the National Health and Nutrition Examination Survey (NHANES) between 2011 and 2018. The study analyzed nine types of urinary heavy metals and three types of blood heavy metals. Survey-weighted logistic regression, restricted cubic spline (RCS) analysis, weighted quantile sum regression (WQS) regression, and Bayesian kernel machine regression (BKMR) model were employed to evaluate the effects of single and mixed heavy metal exposure on DKD. Subgroup analyses were conducted based on age and gender. Mediation analysis was used to assess the mediating effect of the aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio. Additionally, a series of sensitivity analyses were performed. The final analysis included 5,124 individuals (2011–2018), of whom 896 (17.49%) were classified as having DKD. Weighted logistic regression indicated that urinary barium (UBa), urinary cobalt (UCo), urinary cesium (UCs), urinary thallium (UTl), blood cadmium (BCd), and blood lead (BPb) were associated with DKD. RCS analysis indicated a nonlinear relationship between UBa, UCo, UCs, UTl, BPb, and DKD. Both WQS regression and BKMR model consistently demonstrated a negative correlation between urinary mixed heavy metal exposure and the risk of DKD, while blood mixed heavy metal exposure was positively correlated with the risk of DKD, identifying UBa as the primary protective contributor and BCd as the primary risk contributor. Subgroup analysis revealed that age and gender could modify the association between heavy metal exposure and the risk of DKD. Finally, mediation analysis revealed that the AST/ALT ratio played a crucial potential mediating role in the association between heavy metal exposure and the prevalence of DKD. Our findings offer a comprehensive perspective on the relationship between heavy metals (particularly protective UBa and risk-associated BCd) and DKD risk, which holds significant implications for environmental control and early prevention of DKD, it is important to note that our cross-sectional design precludes causal inferences. Future longitudinal studies are needed to establish causality and inform intervention strategies.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-23843-w.

In Barrett's oesophagus (BO), the precursor of oesophageal adenocarcinoma, the adult stratified squamous epithelium is replaced by a simple columnar phenotype. This has been considered metaplasia, i.e. the inappropriate conversion from one adult cell type to another. Alternatively, BO could represent reversion to an embryonic-fetal state when the early foregut is initially lined by simple columnar epithelium. Exploration of this hypothesis has been hampered by inadequate molecular details of human oesophageal development. Here, we adopted single-cell transcriptomic and epigenomic approaches to discover and de-code the cell types that constitute the initial primitive columnar, transitory and subsequently stratified lower oesophageal epithelium. Each stage comprises several previously undefined epithelial subpopulations. Importantly, early foregut columnar epithelial cells share core regulatory and gene expression programmes with BO. Among these, HNF4A is identified as a prominent transcriptional regulator that forms the core of a regulatory network in early foregut columnar cells. These regulatory networks are also central to programmes known to be reactivated in BO. Collectively, these data argue that the path to BO involves reactivation of pathways that define primitive embryonic and fetal epithelial cell states.

Highly discriminative globin gene activation by the non-canonical BAF chromatin remodeling complex.

IntroductionGranulosa cell tumors (GCTs) represent the most common ovarian neoplasms in mares, yet data on their epidemiology, risk factors, and clinical outcomes in Arabian horses are limited. Understanding their prevalence and diagnostic features is crucial for improving fertility management in this breed.MethodsClinical records from 807 Arabian mares housed on 35 stud farms in central Saudi Arabia were retrospectively reviewed to determine the prevalence of GCT and potential risk factors, including age, parity, and anabolic steroid use. Twenty-four confirmed cases were further investigated using clinical examination, ultrasonography, endocrine profiling, and histopathology. Surgical management by unilateral ovariectomy was performed in 20 mares, and postoperative fertility outcomes were documented.ResultsThe overall prevalence of GCT was 0.6%. Logistic regression analysis identified anabolic steroid use as a significant risk factor (Odds Ratio = 13.21, p = 0.0001). Stallion-like behavior was the most frequent clinical manifestation (58.3%), followed by anestrus (33.3%) and persistent estrus (8.3%). Ultrasonography revealed four distinct tumor morphologies, with contralateral ovarian atrophy present in 75% of cases. Histopathology classified tumors into adult type (76.5%) and juvenile type (23.5%). Preoperative testosterone concentrations were elevated and decreased postoperatively in 72.7% of mares. Ovariectomy resulted in an 80% recovery rate, with 68.8% of mares regaining fertility.DiscussionThis study demonstrates that anabolic steroid administration markedly increases the risk of GCT in Arabian mares. Behavioral changes, ultrasonographic appearance, and hormonal profiles remain key diagnostic indicators, while histopathology confirms tumor classification. Surgical excision proved effective, with favorable fertility outcomes in most mares. These findings underscore the importance of early diagnosis and highlight the need for judicious use of anabolic steroids in breeding programs.