Severe pneumonia is the most common cause of acute respiratory distress syndrome (ARDS), and precise and individualized assessment is a prerequisite for improving therapeutic outcomes. Of all bedside assessment tools, respiratory physiological indicators are the most readily available and widely adopted, covering key metrics including gas exchange, respiratory mechanics, respiratory drive, and inspiratory effort. Recent prospective cohort investigations have validated that physiological metrics, including driving pressure, mechanical power, respiratory drive, and inspiratory effort, correlate strongly with mortality among patients with ARDS. Furthermore, thoracic imaging technologies (such as chest CT, ultrasound, and electrical impedance tomography) can accurately evaluate morphological alterations in ARDS lung tissue and dynamically visualize regional lung ventilation function. These tools have demonstrated considerable clinical utility for facilitating precise diagnosis, tailoring individualized ventilation settings, and assessing weaning readiness. Additionally, evaluating inflammatory immune status and biological subphenotypes not only helps elucidate the core pathophysiological mechanisms underlying ARDS secondary to severe pneumonia, but also provides a rationale for precision therapies using medications such as glucocorticoids. Bedside assessment indicators are growing in variety and availability. Artificial intelligence can efficiently integrate and analyze these large-scale multimodal datasets to construct predictive models. These models can track disease progression trajectories, optimize ARDS management, and advance the translation of Clinical Decision Support Systems into clinical practice. This approach represents a vital direction for future research.

Aging is accompanied by progressive immune remodeling and functional decline across multiple organs. However, the role of neutrophils and their heterogeneous states in these processes remains incompletely understood. Here we integrated single-cell RNA sequencing datasets from multiple organs of young and aged mice to characterize aging-associated neutrophil remodeling. We identified organ-dependent changes in neutrophil abundance and state composition, together with neutrophil subsets enriched for inflammatory, oxidative stress, complement, and IL-6-related transcriptional programs. In vitro, exposure to conditioned media from neutrophils isolated from aged mice or IL-6-stimulated neutrophil-like cells increased inflammatory and senescence-associated responses in vascular smooth muscle and hepatocyte-derived cells. Bone marrow single-cell analysis further revealed aging-associated shifts in progenitor composition and transcriptional states, including an old-enriched HPC11 population characterized by enhanced myeloid priming. Silico perturbation analysis nominated FGF didate regulators of HPC subtype-specific transcriptional programs. Together, our study provides a multi-organ single-cell resource for defining neutrophil remodeling during aging and highlights candidate neutrophil states and potential signaling axes associated with age-related inflammatory tissue environments.

Obesity is characterized by adipocyte dysfunction, accompanied by impairments in oxidative metabolism and physical function. Although physical training is known to improve oxidative capacity, body composition, and functional performance, the magnitude of these adaptations may be influenced by several modulatory factors. Among these, circadian rhythm has emerged as a potential determinant of exercise-induced adaptations due to daily fluctuations in metabolic and physiological processes; however, its influence in women with obesity remains unclear. Therefore, this study aimed to investigate the effects of combined training performed at different times of the day (morning vs. evening) on body composition, cardiopulmonary performance, and muscle strength in previously untrained women with obesity.

This randomized clinical trial (NCT06601660) included women with obesity (waist circumference ≥88 cm) aged 18-50 years. Participants were randomly assigned to a control group (CG; n = 13), a morning training group (MT; training performed between 07:00 and 10:00 a.m.; n = 17), or an evening training group (ET; training performed between 06:00 and 09:00 p.m.; n = 19). Assessments conducted before and after the intervention included body composition (InBody® 770), cardiopulmonary performance evaluated by cardiopulmonary exercise testing (CPET), muscle strength assessed by the one-repetition maximum (1RM) test, and cardiovascular parameters evaluated by blood pressure (BP) and heart rate (HR); the last three were performed at both a.m. and p.m. times. Only participants in the MT and ET groups underwent the intervention, which consisted of an 8-week combined training program performed three times per week. Each session included both resistance and aerobic exercise, with progressive increases in exercise intensity and duration throughout the intervention period. Participants assigned to the CG underwent assessments only.

Significant group-by-period interactions were observed for VO_2peak and bench-press and leg-press 1RM, whereas maximal treadmill velocity showed a significant period effect without a significant group-by-period interaction. Bench-press 1RM increased in MT during morning and evening testing by 5.79 and 5.31 kg, respectively, and in ET by 4.97 and 5.50 kg (all p < 0.001; d = 2.37-2.76), with gains in both training groups exceeding those observed in CG. Leg-press 1RM increased in MT by 22.20 and 29.01 kg and in ET by 18.40 and 17.11 kg during morning and evening testing, respectively (p ≤ 0.001; d = 1.13-1.92); however, only MT showed a greater overall change than CG. VO_2peak increased in MT during morning testing [2.42 mL·kg^-1·min^-1 (p = 0.004; d = 1.04)] and in ET during evening testing [1.57 mL·kg^-1·min^-1 (p = 0.048; d = 0.67)]. Maximal treadmill velocity and CPET duration improved over time, but their changes did not differ significantly among groups. Body-composition and cardiovascular adaptations were limited, with waist circumference increasing only in CG.

Eight weeks of combined training performed either in the morning or evening improved maximal muscle strength and cardiopulmonary performance in women with obesity, while producing limited changes in body composition and cardiovascular measures. No consistent evidence of superior adaptations according to training time was observed, suggesting that both schedules can effectively promote health-related adaptations.

Diabetic retinopathy (DR) is the leading cause of vision loss among working-age adults worldwide. AI-assisted automated image reading has effectively alleviated the human resource challenges in large-scale remote screenings, yet there is limited analysis on the impact of complex ocular factors on the diagnostic efficacy of AI.

This study aimed to systematically analyze the impact of multiple ocular factors on the diagnostic efficacy of the EVisionAI system in detecting DR and vision-threatening diabetic retinopathy (VTDR) during large-scale screening of residents with diabetes in resource-limited regions.

This cross-sectional study used a multistage stratified random sampling method to screen residents with type 2 diabetes at primary health centers in resource-limited regions. Data collection involved structured questionnaires (for basic and disease information), hemoglobin A_1c testing, and comprehensive ophthalmic examinations (visual acuity, intraocular pressure, slit-lamp examination, axial length measurement, and fundus photography). Following data collection, 2 ophthalmologists independently graded fundus photographs according to the American Academy of Ophthalmology standards. The influence of various ocular factors on the diagnostic performance of EVisionAI was subsequently evaluated.

Between October 21 and November 12, 2024, 1847 participants with type 2 diabetes (aged 32-91 years) were enrolled, of whom 1748 (94.6%) completed the screening process and 3392 eyes were eligible for DR analysis. Participants had a mean age of 67.17 (SD 8.52) years and mean diabetes duration of 9.13 (SD 6.97) years, with 19.2% (335/1748) having DR and 7.4% (129/1748) having VTDR. Although EVisionAI's diagnostic efficacy was comparable to that of ophthalmologists (sensitivity: 90.61%, 95% CI 87.89%-92.79%; specificity: 98.99%, 95% CI 98.52%-99.31%), some ocular factors-including pupil size, refractive media opacity, and tessellated fundus (TF)-significantly impaired its efficiency. Severe refractive media opacity and TF reduced its sensitivity to 80.95% and 82.86%, respectively, and these factors interfered more with early-stage DR detection than VTDR (97.45% detected), particularly in eyes with severe TF changes (sensitivity decreased to 60.71%). Most notably, severe vitreous degeneration-induced opacity almost invariably led to VTDR misdiagnosis. Additionally, pupil dilation improved the sensitivity of EVisionAI for diagnosing DR (excluding early-stage DR) but had minimal impact on specificity.

EVisionAI achieved high diagnostic accuracy for large-scale DR screening in resource-limited regions, yet its performance for early-stage disease was diminished by severe ocular factors. Optimizing for these factors is therefore essential to maximize its clinical utility in primary care settings with limited specialist access.

Background Albuminuria is an important marker of diabetic kidney disease (DKD) and is associated with adverse renal and cardiovascular outcomes in people with type 2 diabetes mellitus (T2DM). Although sustained hyperglycemia is a recognized contributor to DKD, glycated hemoglobin (HbA1c) does not fully capture short-term glycemic variability. Emerging evidence suggests that hypomagnesemia and altered thyroid function may be associated with albuminuria, but their combined relationships with albuminuria and the possible statistical mediating role of thyroid hormones remain unclear. This study was conducted to identify the associations of albuminuria with glycemic variability, serum magnesium, and thyroid function in T2DM patients. Materials and methods A cross-sectional study included 330 adults aged 30-84 years with T2DM of more than five years' duration. Continuous glucose monitoring (CGM)-derived measures, including mean glucose, glucose standard deviation (SD), coefficient of variation (CV), time in range (TIR), and mean amplitude of glycemic excursions (MAGE), were assessed alongside HbA1c, serum magnesium, free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), and urinary albumin-to-creatinine ratio (UACR). Associations with albuminuria were examined using univariable and multivariable logistic regression, with additional correlation and exploratory regression-based mediation analysis. Ethical approval and written informed consent were obtained. Results Among 330 participants, 208 (63%) had normal UACR, 98 (29.7%) had microalbuminuria, and 24 (7.3%) had macroalbuminuria. Hypomagnesemia was associated with more than twofold higher odds of albuminuria in univariable analysis (odds ratio (OR)=2.26; 95% confidence interval (CI): 1.38-3.70; p=0.001). In Model IV, which was adjusted for demographic variables, higher HbA1c (OR=1.66; 95% CI: 1.34-2.05; p<0.001), SD (OR=1.63; 95% CI: 1.18-2.26; p=0.003), CV (OR=1.06; 95% CI: 1.01-1.10; p=0.016), and MAGE (OR=1.25; 95% CI: 1.07-1.45; p=0.005) were independently associated with higher odds of albuminuria. In contrast, higher FT3 was inversely associated with albuminuria (OR=0.46; 95% CI: 0.28-0.74; p=0.001). TIR, FT4, and TSH were not significantly associated with albuminuria in univariable analysis. HbA1c was negatively correlated with FT3 (ρ=-0.133; p=0.016). Similarly, SD was negatively correlated with FT3 (ρ=-0.227; p<0.001). Exploratory mediation analysis indicated that FT3 statistically accounted for 6.9% of the association between HbA1c and albuminuria and 21.4% of the association between glucose SD and albuminuria. Conclusion Greater glycemic variability and lower FT3 levels were independently associated with albuminuria in patients with T2DM, while hypomagnesemia was associated with albuminuria in univariable analysis. Exploratory mediation analysis suggested that FT3 statistically accounted for a modest proportion of the associations of HbA1c and glucose SD with albuminuria. These findings indicate that CGM-derived variability measures, alongside magnesium status and thyroid function, may provide complementary information in the assessment of DKD. Prospective multicenter studies are required to clarify the temporal relationships and clinical significance of these findings.

Necrotizing soft tissue infections (NSTIs) are rapidly progressive, life- and limb-threatening emergencies requiring immediate surgical source control. Group B Streptococcus (GBS; Streptococcus agalactiae) is a rare cause of NSTIs in adults. We present a 44-year-old woman with poorly controlled diabetes who developed progressive right foot pain and swelling after minor ankle trauma. Examination showed spreading erythema, crepitus, dusky discoloration, malodor, and a deep plantar wound, accompanied by marked leukocytosis and diabetic ketoacidosis. Computed tomography demonstrated infection extending from the forefoot through the ankle into the anterior compartment of the leg, prompting emergent exploration that confirmed extensive NSTI. Two wound specimens obtained before antibiotics yielded heavy GBS growth, whereas deep intraoperative ankle and leg specimens collected after starting antibiotics grew heavy Streptococcus anginosus and moderate Prevotella species. Despite broad-spectrum antibiotics and debridement, transtibial amputation was required. This case highlights a rare GBS-associated polymicrobial NSTI and emphasizes early recognition of progressive soft-tissue findings despite an apparently minor musculoskeletal injury.

Diabetes Mellitus Type 2 (T2DM) is a significant health concern for Hajj pilgrims, with glycaemic control crucial for their well-being during the pilgrimage. Physical health is key to determining istithaah, including HbA1c and fasting blood glucose tests for prospective Hajj pilgrims with type 2 diabetes mellitus.

This study describes HbA1c and fasting blood glucose levels as indicators of glycaemic control among Indonesian prospective Hajj pilgrims diagnosed with T2DM based on laboratory results from medical check-ups for the 2024 departure in Tangerang City, and assesses their association with demographic factors.

A cross-sectional study analyzed HbA1c from 125 pre-departure medical check-ups of 75 female and 50 male prospective Hajj pilgrims. Data were collected from medical records at a public hospital in Tangerang City and from the Hajj Integrated Computer Health System (SISKOHATKES) application in 2024. Statistical analysis was performed using the Chi-square test or Fisher's exact test, as appropriate.

This study showed that most subjects were female, with the most common age group being 18-59 years (adult). The most prevalent health eligibility (istitaah) status was eligible with assistance. More than 50% of Hajj pilgrims with T2DM had comorbid conditions such as hypertension, cardiomegaly, and hyperlipidaemia. The mean HbA1c level was 9.82 ± 2.2%, with most participants exhibiting uncontrolled glycaemic status (HbA1c >7.5%). Similarly, the mean fasting blood glucose level was 197.0 ± 67.8 mg/dL, with the majority also falling within the uncontrolled range (fasting blood glucose >126 mg/dL). There was no significant correlation between HbA1c levels and age or sex.

The majority of prospective Hajj pilgrims with T2DM are uncontrolled in terms of glycaemic status. These findings require comprehensive assessment and management strategies before, during, and after the Hajj pilgrimage to minimize risk and prevent complications.

Mitochondria are central regulators of cellular metabolism, redox homeostasis, and stress adaptation. Mitohormesis refers to an adaptive response in which mild or transient mitochondrial perturbation activates stress-response pathways that subsequently enhance mitochondrial or cellular resilience; however, persistent or excessive stress can overwhelm adaptive capacity and promote mitochondrial dysfunction and tissue injury. Metabolic diseases, including obesity and type 2 diabetes mellitus, are major risk factors for cognitive decline and dementia, and clinical studies have demonstrated associations between metabolic dysfunction, structural brain abnormalities, accelerated brain aging, and impaired cognitive function. However, direct evidence linking mitochondrial dysfunction to neurodegeneration in humans remains limited, with most mechanistic insights derived from experimental animal models and cultured neuronal systems. Experimental evidence indicates that chronic metabolic stress can disrupt mitochondrial quality control and proteostasis, increase mitochondrial reactive oxygen species production, and promote neuroinflammation and neuronal dysfunction. Conversely, adaptive mitochondrial stress responses can preserve mitochondrial integrity and cellular resilience through coordinated regulation of the integrated stress response, mitochondrial quality-control mechanisms, lysosomal-mitochondrial crosstalk, extracellular vesicle-mediated communication, and inter-organ signaling. In Alzheimer's disease, mitochondrial dysfunction and amyloid-β/tau pathology may interact bidirectionally, potentially generating self-reinforcing cycles of neuronal injury. Lifestyle and pharmacological interventions-including exercise; caloric restriction; nutritional ketosis; and the use of metformin, sodium-glucose cotransporter 2 inhibitors, and glucagon-like peptide-1 receptor agonists-have been associated with adaptive mitochondrial and metabolic responses involving AMP-activated protein kinase, nuclear factor erythroid 2-related factor 2, mitochondrial biogenesis, mitophagy, and redox signaling. However, evidence that mitohormesis directly mediates their beneficial effects varies substantially across interventions and remains predominantly indirect or hypothesized in humans. Moreover, the discrepancy between encouraging preclinical findings and clinical outcomes highlights important translational barriers, including the lack of validated biomarkers, uncertainty regarding optimal stress intensity and timing, and tissue- and disease-specific differences in adaptive capacity. Collectively, current evidence supports mitohormesis as a conceptual framework for integrating mitochondrial stress adaptation, metabolic dysfunction, and neuronal resilience rather than as an established unifying mechanism underlying neurodegeneration. Defining the conditions under which mitochondrial stress is adaptive, identifying reliable biomarkers of mitohormesis, and determining whether these responses can be safely and effectively modulated in humans will be essential for establishing its therapeutic relevance in metabolic and neurodegenerative diseases.

Gestational diabetes mellitus (GDM) is commonly diagnosed at 24-28 weeks of gestation; however, metabolic susceptibility that precedes dysglycemia may emerge earlier. We examined whether the rate of early pregnancy body mass index (BMI)-derived estimated body fat percentage (eBFP) change was associated with subsequent GDM, and whether this association differed according to an early hepatic-metabolic phenotype defined by the natural log-transformed fatty liver index (FLI_Ln). This secondary analysis used de-identified data from a prospective Korean pregnancy cohort and included 583 singleton pregnant women without pregestational diabetes, of whom 37 developed GDM. eBFP was estimated from BMI and maternal age, and the early-pregnancy eBFP change rate was calculated from pre-pregnancy to 10-14 weeks of gestation and scaled so that each one-unit increase represented a 0.1 percentage-point/week higher change rate. Multivariate logistic regression, restricted cubic splines, threshold analysis, subgroup interaction testing, exploratory mediation analysis, and propensity score-matched sensitivity analyses were also performed. After adjustment for maternal age, parity, pre-pregnancy BMI, a higher eBFP change rate was associated with increased odds of subsequent GDM (odds ratio [OR], 1.58; 95% confidence interval [CI], 1.14-2.21; P = 0.006), with an approximately linear dose-response pattern. The FLI_Ln showed a nonlinear association with GDM, with a data-derived threshold of 2.90. The eBFP change rate-GDM association was evident among women with FLI_Ln ≥2.90 (OR, 1.82; 95% CI, 1.22-2.71; P = 0.004), but not among those with FLI_Ln <2.90 (OR, 0.51; 95% CI, 0.22-1.20; P = 0.123; P for interaction = 0.018). Exploratory mediation analyses suggested that FLI_Ln partially accounted for the observed association, although the magnitude of this mediation was imprecisely estimated. In this secondary cohort analysis, a faster early-pregnancy BMI-derived adiposity change was associated with a higher risk of GDM, particularly among women with an elevated composite hepatic-metabolic phenotype. These findings support an early adiposity-hepatic metabolic susceptibility framework for GDM risk enrichment but require external validation before clinical application.

Vitamin D deficiency is a global health issue linked to musculoskeletal disorders, including osteoporosis and arthritis. Despite its critical role in bone and immune health, large-scale comparisons of vitamin D status between outpatient and inpatient populations remain limited.

This study aimed to compare vitamin D levels in patients with and without arthritis or osteoporosis across outpatient and inpatient settings and evaluate their associations with clinical outcomes.

We performed a retrospective cross-sectional analysis of 37800 adults treated at the Department of Orthopedics in Nanjing Drum Tower Hospital from 2015 to 2020. Serum 25(OH)D concentrations were categorized as normal, low, or deficient. Patients were stratified by diagnosis (arthritis and osteoporosis) and care setting (outpatient vs. inpatient). Statistical comparisons were made using t-tests, Chi-square tests, and log-binomial regression adjusted for age, sex, the alternate musculoskeletal diagnosis, and osteocalcin. Diabetes mellitus was only consistently available for inpatients and was therefore handled as a descriptive inpatient characteristic rather than in the outpatient characteristic and regression models.Adjusted relative risks (RRs) for arthritis and osteoporosis were estimated according to vitamin D status, with normal vitamin D as the reference category, using log-binomial regression adjusted for age, sex, osteocalcin, and the alternate musculoskeletal diagnosis where applicable.

Suboptimal vitamin D status (low or deficient levels) was widespread across both settings, affecting 52% of outpatients and 41% of inpatients. The overall mean 25(OH)D was 26.25 ± 7.14 ng/mL in outpatients and 27.38 ± 6.58 ng/mL in inpatients. Among outpatients, those with arthritis exhibited higher deficiency rates (16.2% vs. 13.6% in non-arthritis) and significantly elevated arthritis risks (RR ranging from1.24 to 1.32). Among inpatients, however, the arthritis analysis was limited by the small number of cases (n=176) and wide confidence intervals (RR for deficiency=1.08, 95% CI 0.65-1.70), so the finding is inconclusive and does not support the association. Deficiencies were particularly pronounced in osteoporosis cases: 26.3% of osteoporotic outpatients were deficient (vs.12.8% controls; RR = 2.79), while inpatients with osteoporosis also showed higher deficiency (13.7% vs. 10.2%; RR = 1.50), with both differences statistically significant (p<0.001).

Vitamin D deficiency was common, particularly among osteoporosis patients in outpatient settings. Associations were strongest for outpatient osteoporosis, while the inpatient arthritis estimates were limited by the small number of cases. These findings suggest that targeted assessment of vitamin D status in patients with osteoporosis or arthritis, rather than universal screening, may help identify individuals at higher risk of deficiency and related musculoskeletal complications.