Neural tube defects (NTDs) result from failure of neural tube closure and remain a major cause of neonatal morbidity worldwide. Genetic, epidemiological, and animal studies have identified multiple NTD‑associated factors, but the mechanisms underlying human NTDs remain incompletely understood. Direct investigation of human NTD pathogenesis is limited by restricted access to embryonic tissues and by species differences in animal models. Conventional two‑dimensional cultures also fail to capture dynamic developmental processes such as neuroepithelial folding, tissue morphogenesis, and spatial patterning. This review synthesizes current evidence on the genetic, environmental, and morphogenetic mechanisms associated with NTDs and evaluates the applications and limitations of human organoid and organoid-on-chip models in this field. NTD‑associated genetic and environmental perturbations can produce measurable cellular and morphological phenotypes in organoid systems. These phenotypes support functional assessment of candidate pathogenic factors and mechanistic investigation. Microfluidic and bioengineering approaches further improve control over geometric boundaries, mechanical cues, and morphogen gradients, while enhancing model reproducibility. Overall, human organoid and organoid‑on‑chip platforms expand the experimental toolkit for NTD research and show potential for developmental toxicity assessment, risk‑factor screening, and patient‑specific disease modeling.

IntroductionNon-communicable diseases (NCDs), particularly hypertension and diabetes, pose significant health challenges in India, especially in low- and middle-income countries. In Tamil Nadu, these diseases have led to high mortality rates, with alarmingly low control rates despite existing healthcare initiatives. This study aim to evaluate community control rates of hypertension and diabetes in the Villupuram and Cuddalore districts, focusing on medication adherence and metabolic control.Subjects and MethodsA cross-sectional survey was conducted in November 2023 involving 1,572 participants aged 18-69 years who had been receiving treatment for hypertension and diabetes for over six months. Using the MTM line list, we employed a cluster sampling design, selecting one block from each district. Blood pressure and HbA1c levels were measured to determine control rates, and a structured questionnaire collected sociodemographic data and medication adherence information. Data analysis was performed using Stata version 16, focusing on descriptive statistics.ResultsOut of 1,572 participants, 757 had hypertension and 738 had diabetes, yielding an overall response rate of 95%. Medication adherence was reported at 75.6% for individuals with hypertension and 76.2% for those with diabetes. Control rates were notably low, with only 49.1% of hypertensive participants achieving optimal blood pressure control and 25.7% of diabetics maintaining ideal glycaemic levels. Additionally, over 70% of participants were classified as overweight or obese.ConclusionDespite reasonable medication adherence, the control rates for hypertension and diabetes in Tamil Nadu are inadequate. The high prevalence of obesity highlights the need for community-based interventions, such as patient support groups and lifestyle modification programs, to enhance treatment adherence and improve health outcomes. A follow-up survey is planned to evaluate the effectiveness of these initiatives.

Growing evidence suggests that imbalances occurring within the human microbiota and deregulation of the host immune response may play a significant role in the development of neurodegenerative diseases.

A comprehensive narrative review of the latest experimental, clinical, and epidemiological insights was conducted to explore the associations among oral dysbiosis, including periodontitis and peri-implantitis, a low-grade inflammatory phenotype, and biological pathways that may contribute to the onset of neuroinflammation and neuropathologies.

Periodontitis is a chronic inflammatory non-communicable disease driven by subgingival dysbiosis, increasingly linked not only to progressive bone and tooth loss but also to a broad range of systemic chronic non-communicable diseases. Indeed, the persistent burden of deregulated chronic inflammation not only exacerbates periodontal tissue destruction but also promotes a low-grade inflammatory phenotype that may predispose patients to a spectrum of degenerative diseases, such as neurodegenerative disorders. In contrast, evidence regarding peri-implantitis remains comparatively limited and indirect, although emerging data indicate potential systemic inflammatory and cognitive implications.

Elucidating the intricate interactions between oral dysbiosis, periodontal diseases, chronic inflammation, and neurodegeneration is essential for understanding oral health's systemic implications for neurodegenerative and age-related diseases. Current evidence supports an association between oral dysbiosis, chronic oral inflammation, and pathways relevant to neurodegeneration, particularly for periodontitis. However, important knowledge gaps remain, especially concerning peri-implant diseases, where human data are limited.

Effective management strategies targeting periodontal and peri-implant dysbiosis and restoring the immune imbalance may offer novel avenues for promoting healthy aging and preventing neuropathic morbidities.

Reliable biomarkers for discriminating allergic rhinitis with asthma (ARA) from related allergic airway phenotypes remain lacking in pediatric populations. We aimed to identify and validate circulating metabolic biomarkers of ARA.

Serum samples from 380 participants, including healthy controls (HC), allergic rhinitis (AR), asthma (AS), and ARA, underwent untargeted carboxylomics profiling using SPCSDCarboxyl. Candidate biomarkers were evaluated in mouse models and validated in an independent cohort (n = 125) using targeted carboxylomics. Biomarker performance was assessed using multivariate and machine-learning approaches.

ARA was associated with altered circulating odd-chain fatty acids (OCFAs), with valeric, heptanoic, nonanoic, undecanoic, and isovaleric acids showing consistent increased across cohorts. Heptanoic, nonanoic, and undecanoic acids demonstrated excellent discrimination of ARA from HC, with areas under curve (AUC) of 0.96, 0.98, and 0.94, respectively. However, these three OCFAs were broadly elevated across all allergic airway phenotypes and lacked ARA specificity. Least absolute shrinkage and selection operator (LASSO) regression identified valeric and undecanoic acids as complementary discriminatory features for ARA versus AR and AS. Among valeric acid showed the most phenotype-discriminatory performance, with an AUC of 0.72 for ARA versus AR and 0.64 for ARA versus AS. OCFA levels correlated significantly with inflammatory indices and pulmonary function, and comparable alterations were confirmed in mouse models.

These findings identify a pediatric ARA-specific OCFA signature of a distinct immunometabolic endotype involving propionyl-CoA metabolism and fatty acid oxidation. Valeric acid uniquely discriminated ARA from isolated AR, supporting its potential as a serum reference marker; combination with undecanoic acid or clinical parameters may further improve diagnostic performance.

Cardiac fibrosis is a critical pathological process driving the progression of heart failure, characterized by excessive extracellular matrix deposition, collagen network remodeling, and expansion of the myocardial interstitium. While fibrosis may reflect a reparative response to tissue injury, it can also signify a maladaptive remodeling process that progressively impairs cardiac structure and function. Cardiac fibroblasts and myofibroblasts serve as the principal effector cells responsible for matrix accumulation, whereas cardiomyocytes and immune cells contribute to fibrotic expansion through inflammatory signaling, paracrine communication, and microenvironmental regulation. Transforming growth factor-β, the renin-angiotensin-aldosterone system, inflammatory cytokines, mechanical stress, and metabolic disturbances collectively orchestrate a profibrotic signaling network. By regulating extracellular matrix synthesis, degradation, and crosslinking, these pathways promote myocardial stiffening and functional decompensation. In this review, we discuss the histopathological patterns of cardiac fibrosis across various pathological contexts, the major cellular contributors, and the core molecular mechanisms involved, while summarizing current advances in diagnostic evaluation and translational therapeutic strategies. We further discuss the context-dependent role of sirtuin 3 (SIRT3), a mitochondrial nicotinamide adenine dinucleotide (NAD⁺)-dependent deacetylase, in linking mitochondrial homeostasis, oxidative stress, metabolic adaptation, and profibrotic signaling. More precise antifibrotic strategies require better definition of fibroblast states, fibrosis activity, and disease-specific remodeling patterns.

This study aimed to evaluate the diagnostic utility of quantitative beta-trace protein (β-TP) as an early biomarker for identifying postoperative cerebrospinal fluid (CSF) leaks following endoscopic endonasal approach (EEA) surgery for sellar tumors.

A total of 401 patients with sellar tumors who underwent EEA surgery at Huashan Hospital between April 2023 and July 2025 were enrolled. For postoperative hemostasis, expandable nasal sponges were placed in the posterior nasal cavity. Sponge extracts were collected on postoperative Day 2 to measure quantitative β-TP concentrations using an immunoturbidimetric assay. Receiver operating characteristic (ROC) curve analysis was performed to determine the optimal β-TP cutoff value and evaluate its diagnostic performance.

Postoperative CSF leaks were confirmed in 16 patients (4.0%). The median β-TP concentration in the CSF leak group was significantly higher than in the non-CSF leak group (4.54 vs. 0.419 mg/L; p < 0.001). The area under the ROC curve was 0.941. Based on the maximum Youden index, the optimal diagnostic cutoff value for postoperative CSF leaks was established at 2.07 mg/L. This cutoff value yielded a sensitivity of 93.75%, a specificity of 99.48%, a positive predictive value of 88.24%, and a negative predictive value of 99.74%.

This study is the first to demonstrate that quantifying β-TP concentrations in nasal sponge extracts provides a highly sensitive and specific method for diagnosing CSF leaks following EEA surgery. This approach offers distinct advantages for detecting occult CSF leaks, providing an effective threshold to guide early diagnosis and targeted clinical management.

Quiet quitting (QQ), the voluntary reduction of discretionary effort while maintaining minimum job requirements, has become a pressing concern in healthcare. Understanding its prevalence and drivers is essential for sustaining workforce well-being. This systematic review and meta-analysis aimed to estimate the pooled mean of QQ among healthcare professionals (HCPs) and identify associated factors.

This systematic review was carried out according to PRISMA guidelines by searching in three international databases including Web of Science, Scopus, and PubMed from 2020 to 2026. Quantitative data were synthesized using random-effects models. Subgroup analyses were performed based on geography, professional role, and healthcare setting. Factors associated with QQ were categorized using the expanded Job Demands-Resources (JD-R) framework.

Thirty-one studies were included in the qualitative synthesis, with 25 studies (n = 14,508 HCPs) included in the meta-analysis. The pooled mean QQ score was 2.49 (95% CI: 2.37-2.61), with significant heterogeneity (I² = 99.2%). Subgroup analyses indicated higher QQ levels among nurses compared to other professionals and among hospital-based staff compared to those in primary care. Factors associated with QQ were clustered into four domains: (1) job demands (e.g., burnout, excessive workload, and workplace toxicity), (2) job resources (e.g., poor leadership, lack of organizational justice, and inadequate professional support), (3) personal resources (e.g., low resilience, poor coping strategies), and (4) contextual/demographic characteristics (e.g., younger age, shorter tenure). Sensitivity analyses confirmed the robustness of these findings.

The findings suggest that QQ is an emerging and multifactorial phenomenon among HCPs, influenced primarily by structural and relational workplace factors. However, given the substantial heterogeneity, limited geographical representation, and variability in measurement approaches across studies, the pooled findings should be interpreted cautiously.

Healthcare organizations should prioritize "relational" resources over extrinsic rewards. Monitoring early signs of disengagement and implementing transformational leadership models can help prevent the escalation of QQ into burnout or turnover, thereby sustaining high-quality patient care.

Aim: Type 1 diabetes mellitus (T1DM) is the most common endocrine disorder affecting children and adolescents worldwide. Glycemic control is the ultimate goal of diabetes management, and poor glycemic control is associated with serious short- and long-term complications. Only a few studies have addressed this problem in Cameroon. This study aimed to identify the determinants of glycemic control of T1DM in children and adolescents living in the three northern regions of Cameroon.

Materials and Methods: This was a descriptive and analytical cross-sectional study conducted on 100 children and adolescents with type 1 diabetes followed up in the three T1DM management centers of the CDiC program in the northern regions of Cameroon, from November 2016 to March 2017. Glycemic control was assessed on the basis of glycosylated hemoglobin (HbA1c) levels, according to the current ADA Standards of Care in Diabetes-2025 and ISPAD Clinical Practice Consensus Guidelines 2022, both of which recommend a universal target of HbA1c ≤7.0% (≤53 mmol/mol) for all children and adolescents with type 1 diabetes, regardless of age group. Data were entered into CDC Epi-info™ version 7.2 software, then exported to IBM SPSS Statistics™ version 20.0 for analysis. Descriptive and inferential statistics were used. Bivariate analysis was followed by binary logistic regression to calculate adjusted odds ratios (AORs) for determinants of glycemic control, and a p-value <0.05 was considered statistically significant.

Results: The 100 participants were predominantly male (73%), with a mean age of 16.59 ± 2.54 years. The median HbA1c value was 10.08% [8.7-11.63], reflecting very poor overall glycemic control. Applying the current unified ADA/ISPAD target of ≤7.0% (53 mmol/mol), only 19% of participants achieved their glycemic targets - a proportion markedly lower than figures reported in high-income countries such as the United States (approximately 21-25% in the T1D Exchange Registry). In bivariate analysis, variables significantly associated with glycemic control included: being followed in the Adamaoua region (OR=0.21 [0.07-0.62]; p=0.003), living within 20 km of the diabetes clinic (OR=4.4 [0.94-20.84]; p=0.04), and duration of diabetes less than 2 years (OR=2.90 [1.06-8.30]; p=0.03). In multivariate logistic regression, belonging to the Adamaoua region, a treatment regimen of more than 2 injections per day, living less than 20 km from the management clinic, fewer than three episodes of severe hypoglycemia in the last 6 months, duration of diabetes less than 2 years, and participation in more than three therapeutic education sessions were associated with achieving glycemic targets.

Conclusions: The majority of children and adolescents with T1DM in the northern regions of Cameroon had poor glycemic control, with only 19% achieving the current unified target of HbA1c ≤7.0% (≤53 mmol/mol). Belonging to the Adamaoua region, intensive insulin therapy (>2 injections/day), proximity to the care center (<20 km), fewer severe hypoglycemic episodes, shorter disease duration (<2 years), and regular therapeutic education were identified as factors associated with good glycemic control. Although global innovations such as hybrid closed-loop insulin delivery systems and teplizumab represent transformative advances in T1D management, these technologies remain inaccessible in the study setting. Intensification of therapeutic education, creation of satellite CDiC centers, and progressive adoption of affordable monitoring technologies are urgently needed.

Adolescent diabetes mellitus (DM) constitutes a significant global public health challenge. This study seeks to quantify the burden of DM in adolescents aged 10-19 years from 1990 to 2023 and to forecast trends in incidence, prevalence, mortality, and disability-adjusted life years (DALYs) through 2040.

Epidemiological data for DM among adolescents in 204 countries and territories were obtained from the Global Burden of Disease (GBD) 2023 database. The global burden was evaluated using age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), age-standardized mortality rate (ASMR), and age-standardized DALY rate (ASDR), stratified by region, sex, age, and Socio-demographic Index (SDI). Health inequality was assessed using the slope index of inequality (SII) and concentration index (CI). Future trends were forecast using an autoregressive integrated moving average (ARIMA) model with model-specific validation (AICc, Ljung-Box test).

From 1990 to 2023, global adolescent DM burden increased substantially. ASIR, ASPR, and ASDR rose consistently, whereas ASMR remained relatively stable with a slight decline. In 2023, an estimated 6.07 million adolescents were living with DM (ASPR: 458.07 per 100,000). The highest ASPR was observed in low-SDI regions (482.25 per 100,000), followed by high-SDI regions (442.81 per 100,000). Low-SDI regions also carried the highest DALY and mortality burdens. Males progressively exceeded females in both incidence and prevalence by 2023, although this observed sex reversal may partly reflect changes in screening and diagnostic practices. The overall burden increase was primarily driven by adolescents aged 15-19 years. ARIMA forecasts indicate that ASIR, ASPR, and ASDR are projected to continue increasing through 2040, while ASMR is expected to remain low and stable.

The burden of adolescent DM increased considerably from 1990 to 2023, with marked heterogeneity by age, sex, and geography. The rising non-fatal burden (incidence, prevalence, DALYs) contrasts with stable mortality, suggesting improvements in acute care alongside growing morbidity. Persistent health disparities and projected increases underscore the need for age-, sex-, and region-specific public health strategies.

Type 2 diabetes mellitus (T2DM) may influence clinical outcomes and inflammatory responses after deep brain stimulation (DBS) in patients with Parkinson's disease (PD). This study compared postoperative clinical and cytokine changes in patients with and without T2DM.

This observational study included 156 patients with PD undergoing first-time bilateral subthalamic nucleus DBS (78 with T2DM and 78 without T2DM). MDS-UPDRS III scores, levodopa equivalent daily dose (LEDD), Chinese Mini-Mental State Examination (CMMS) scores, BDI scores, and serum IL-1β, IL-10, and TNF-α levels were assessed before surgery and at 1 and 6 months after surgery. Exploratory analyses examined baseline HbA1c and individual cytokine trajectories.

Before surgery, the T2DM group had a higher BMI and LEDD and lower CMMS scores, whereas no statistically significant between-group differences were observed in Med OFF MDS-UPDRS III scores or cytokine levels. Both groups showed postoperative reductions in MDS-UPDRS III and LEDD. At 6 months, no statistically detectable between-group difference in motor improvement rate was observed (P = 0.667). Between-group cytokine change estimates were small, but 95% confidence intervals crossed zero and did not establish equivalence. Exploratory analyses did not identify clear associations of baseline HbA1c or individual cytokine trajectories with 6-month motor outcome.

In this selected cohort, T2DM was not associated with a statistically detectable reduction in short-term motor benefit after DBS. The observed cytokine changes were temporally associated with postoperative follow-up and should not be interpreted as evidence of a direct anti-inflammatory effect of DBS.