Category: Nevin Manimala

Diabetol Metab Syndr. 2025 May 20;17(1):161. doi: 10.1186/s13098-025-01724-6.

ABSTRACT

OBJECTIVE: This study aimed to construct a scientific, accurate, and readily applicable clinical all-cause mortality prediction model for patients with metabolic dysfunction-associated steatotic liver disease (MASLD) to enhance the efficiency of disease management and improve patient prognosis.

METHODS: This study was a retrospective cohort study based on the National Health and Nutrition Examination Survey database. The 17,861 participants diagnosed with MASLD were randomly assigned to either a training cohort (n = 12,503) or a validation cohort (n = 5358). Potential predictors were subjected to LASSO regression analysis, and independent risk factors were subsequently identified through multivariate Cox regression analysis. An all-cause mortality prediction model was constructed based on the significant predictors, and a nomogram was generated to illustrate the survival probability of patients at various time points. The model’s performance was evaluated using receiver operating characteristic (ROC), calibration, and decision curve analysis (DCA) curves.

RESULTS: A multiple Cox regression analysis identified several independent predictors significantly influencing all-cause mortality in patients with MASLD. These included gender, age, smoking status, hypertension, red blood cell count, albumin, glutamyl transpeptidase, glycosylated hemoglobin, and creatinine. The constructed predictive model demonstrated high accuracy in the training and validation cohorts, with AUC values approaching 0.85 at 3, 5, and 10 years, respectively. Calibration and DCA curves were employed to verify the stability and generalizability of the model.

CONCLUSIONS: We successfully constructed and validated an all-cause mortality prediction model for MASLD patients. This model provides a powerful tool for clinical risk assessment and treatment decision-making.

PMID:40394710 | DOI:10.1186/s13098-025-01724-6

Trials. 2025 May 20;26(1):166. doi: 10.1186/s13063-025-08865-z.

ABSTRACT

BACKGROUND: Type 2 diabetes and prediabetes represent significant global health challenges, with physical activity (PA) being essential for disease management and prevention. Despite the well-documented benefits, many individuals with (pre)diabetes remain insufficiently active. General practitioners (GP) provide an accessible platform for delivering interventions; however, integrating PA interventions into routine care is hindered by resource constraints.

OBJECTIVES: The ENERGISED trial aims to address these barriers through an innovative GP-initiated mHealth intervention combining wearable technology and just-in-time adaptive interventions.

METHODS: The ENERGISED trial is a pragmatic, 12-month, multicentre, randomised controlled trial, assessing a GP-initiated mHealth intervention to increase PA and reduce sedentary behaviour in patients with type 2 diabetes and prediabetes. The primary outcome is daily step count, assessed via wrist-worn accelerometry. The primary analysis follows the intention-to-treat principle, using mixed models for repeated measures. Missing data will be handled under the missing-at-random assumption, with sensitivity analyses exploring robustness through reference-based multiple imputation. The trial incorporates the estimand framework to provide transparent and structured treatment effect estimation.

DISCUSSION: This statistical analysis plan outlines a robust approach to addressing participant non-adherence, protocol violations, and missing data. By adopting the estimand framework and pre-specified sensitivity analyses, the plan ensures methodological rigour while enhancing the interpretability and applicability of results.

CONCLUSIONS: The ENERGISED trial leverages innovative mHealth strategies within primary care to promote PA in individuals with (pre)diabetes. The pre-specified statistical framework provides a comprehensive guide for analysing trial data and contributes to advancing best practices in behavioural intervention trials for public health.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05351359 . Registered on April 28, 2022.

PMID:40394706 | DOI:10.1186/s13063-025-08865-z

J Exp Clin Cancer Res. 2025 May 20;44(1):153. doi: 10.1186/s13046-025-03407-6.

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) is a highly aggressive malignancy with limited treatment options in advanced stages. While c-Met is a promising therapeutic target in HCC, identifying patients who will benefit from c-Met inhibitors remains a significant challenge. This study aimed to investigate the role of HHLA2, a B7 family member, in HCC and its potential as a liquid biopsy marker for c-Met inhibitor therapy.

METHODS: HHLA2 expression was analyzed in clinical HCC samples and public databases. In vitro studies using HCC cell lines assessed HHLA2’s impact on proliferation, migration, invasion, and angiogenesis. In vivo studies using mouse models (orthotopic xenografts and hydrodynamic tail vein injection) evaluated HHLA2’s role in tumor growth and metastasis. Mass spectrometry, co-immunoprecipitation, split-luciferase, and ELISA assays were used to investigate HHLA2-c-Met interactions. Patient-derived organoids (PDOs) were used to assess drug response. Statistical analyses included Student’s t-tests, ANOVA, and Cox regression.

RESULTS: HHLA2 was found to be upregulated in HCC and associated with advanced disease, aggressive clinicopathological features, and poor prognosis. HHLA2 interacted with and constitutively activated c-Met, leading to increased expression of MMP9 and VEGFA, enhancing HCC cell proliferation, invasion, and angiogenesis. HHLA2 also suppressed hepatic natural killer cell infiltration in vivo. Inhibition of c-Met with PHA665752 effectively reversed HHLA2-mediated tumor-promoting effects in vitro and in vivo. HHLA2 expression in HCC tissues correlated with c-Met phosphorylation, and HHLA2 could be detected in the serum of patients with high tumor HHLA2 levels. PDOs with high HHLA2 expression exhibited increased sensitivity to c-Met inhibition.

CONCLUSIONS: HHLA2 acts as an oncogene in HCC by activating c-Met, promoting tumor progression and metastasis. HHLA2 expression correlates with c-Met activation and predicts poor prognosis in HCC patients. Importantly, HHLA2 can serve as a stratification marker for c-Met inhibitor therapy, potentially enabling a personalized approach to improve therapeutic outcomes in this challenging disease.

PMID:40394703 | DOI:10.1186/s13046-025-03407-6

BMC Chem. 2025 May 20;19(1):134. doi: 10.1186/s13065-025-01501-6.

ABSTRACT

Acrylamide (ACM) is a food processing contaminant classified as a probable genotoxic and carcinogenic substance for humans. The rapid and economical determination of ACM in food products poses a major challenge for food safety. This research intended to fabricate a simple, selective, and cost-effective polymeric-coated graphite sensor. This potentiometric sensor is suitable for direct and in situ ACM analysis in food products without tedious sample pretreatment procedures. The sensor was successfully developed based on the ion association complex of the ACM cation with sodium tetraphenylborate (TPB) anion as an ion exchange site, using dibutyl phthalate (DBP) as a plasticizer. The sensor demonstrated a fast, stable, selective, and linear Nernstian response (57.45 mV/decade) over a wide concentration range from 1 × 10^-7 to 1 × 10^-1 M of ACM, with a detection limit of 1 × 10^-8 M. The sensor’s selectivity behavior, response time, lifetime, pH working range, and fundamental validation parameters were assessed. Compared to a published chromatographic method, the developed sensor operated effectively to determine the ACM content in several food products. Greenness and whiteness were also assessed for the developed sensor, confirming that it is an excellent green and cost-effective option. Furthermore, the developed sensor was compared statistically with recently published ACM sensors to ensure optimal performance.

PMID:40394682 | DOI:10.1186/s13065-025-01501-6

Orphanet J Rare Dis. 2025 May 20;20(1):240. doi: 10.1186/s13023-025-03650-2.

ABSTRACT

BACKGROUND: Williams Syndrome (WS) is a neurodevelopmental disorder caused by microdeletion on chromosome 7. Hearing loss (HL) is common in this population but is rarely taken seriously. Previous studies had small sample sizes and mixed conclusions, and few studies have investigated HL in children with WS.

OBJECTIVES: To investigate audiological characteristics of children with WS, analyze the influence factors, and to provide scientific basis for further improvement of ear and hearing care in children with WS.

METHODS: Children with WS aged 0-18yrs, followed up in the Department of Pediatric Healthcare of the Children’s Hospital of Zhejiang University School of Medicine from June 2020 to June 2024 were enrolled in this study. Children aged 0-18yrs who came in the same period for health examination were matched as the control group. Both groups underwent a series of audiological examinations such as tympanogram, distortion product otoacoustic emission (DPOAE), auditory brainstem response (ABR) and pure-tone audiometry (PTA), to analyze the audiological characteristics of WS at different ages, and their difference with control group. Tympanogram and DPOAE were suggested to retest 1 year later and the results of first and second test were also compared.

RESULTS: Tympanogram and DPOAE were completed in 130 WS and control subjects, ranging in age from 1.0 to 12.4 years in the WS group and 0.8-13.1 years in the control group. The passing rate of tympanogram and DPOAE in WS was significantly decreased when compared with control group (p < 0.05), and these differences were found in all age groups. The lower DPOAE passing rate still remain after the tympanogram abnormal data were excluded. The SNR of 2000-5000 Hz were statistically lower in children with WS after tympanogram, DPOAE abnormal data were excluded. Tympanogram and DPOAE were rested in 25 WS 1 year later, and no significant difference was found in the passing rate of these test. ABR tests were completed in 28 WS and 44 control subjects, ranging in age from 0.7 to 5.2 years in the WS group and 0.4-5.2 years in the control group. Threshold of ABR in WS was higher than control group. The latency of wave I, III and the interpeak latency I-III in WS were significantly longer (p < 0.05), and the interpeak latency III-V was significantly shorter than that in control group (p < 0.05). PTA were completed in 20 WS and 28 control subjects, ranging in age from 5.9 to 13.7 years in the WS group and 5.9-12.5 years in the control group. 50% of WS was assessed as HL by PTA, with conductive hearing loss (CHL) in 60%, sensorineural hearing loss (SNHL) in 20% and mixed hearing loss (MHL) in 20%, most were mildly. The threshold of 250-8000 Hz in WS group were significantly higher than that in control group (p < 0.05), either in air or bone conduction.

CONCLUSIONS: This study revealed that children with WS frequently exhibit middle and inner ear dysfunction, often accompanied by HL or subclinical cochlear impairment, which can emerge before age 3. Prolonged ABR latency indicates delayed auditory nerve myelination, while shortened interpeak latency III-V may serve as an electrophysiological marker in this population. Long-term, regular hearing follow-up is recommended to enable early HL detection and timely treatment of contributing conditions.

PMID:40394675 | DOI:10.1186/s13023-025-03650-2

J Orthop Surg Res. 2025 May 20;20(1):489. doi: 10.1186/s13018-025-05877-y.

ABSTRACT

PURPOSE: To quantitatively analyze the structural changes of the knee in patients with neglected developmental dysplasia of the hip (DDH).

METHODS: PubMed, Embase, Web of Science, and Cochrane Library databases were searched to identify studies comparing the morphological parameters of the knee between DDH patients and healthy individuals. Data on rotational and mechanical parameters of the lower limb, rate of occasional anterior knee pain (AKP), and knee morphological parameters, were extracted. Review Manager and R statistic software were used to perform the statistical analysis.

RESULTS: Nine studies with a total of 790 legs in 521 neglected DDH patients and 431 legs in 303 health subjects were included. Patients were predominantly female (88.3%). The Crowe classification is most commonly used to assess the severity of DDH. The total incidence of occasional AKP ranged from 8.6 to 20.6%, with an overall pooled rate of 14.4% (95%CI = 9.8-19.8%). In patients with neglected DDH, significant increases (P < 0.0001) were observed in femoral anteversion (weighted mean: 39.1° vs. 17.7°), knee torsion (weighted mean: 9.0° vs. 1.6°), and the vertical dimension of the medial femoral condyle (weighted mean: 13.8 mm vs. 11.6 mm), along with a significant decrease in the lateral distal femoral angle (weighted mean: 82.1° vs. 84.8°), which can lead to torsion deformity of the lower limb and valgus inclination of the distal femoral articular surface. Compared with the intact subjects, DDH knees demonstrated an increased sulcus angle (weighted mean: 144.9° vs. 137.5°; P < 0.0001), decreased trochlear depth (weighted mean: 3.1 mm vs. 4.5 mm; P < 0.0001), increased lateral shift of the patella (5.1 mm vs. 3.8 mm, P = 0.06), and increased patellar tilt angle (weighted mean: 18.2° vs. 13.2°; P < 0.0001). These findings were associated with developmental dysplasia of femoral trochlear and patellar instability.

CONCLUSION: Developmental dysplasia of the hip leads to patellar malalignment and developmental changes in the bony anatomy of the knee joint, including the development of a valgus deformity of the lower extremity and trochlear dysplasia. These findings may be associated with patellar instability.

LEVEL OF EVIDENCE: III, systematic review.

REGISTRATION: This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42025640292).

PMID:40394669 | DOI:10.1186/s13018-025-05877-y

Radiat Oncol. 2025 May 20;20(1):81. doi: 10.1186/s13014-025-02663-2.

ABSTRACT

INTRODUCTION: Breast cancer-related lymphedema (BCRL) is a debilitating condition that affects a significant proportion of breast cancer survivors, profoundly impacting their quality of life. While many studies have investigated the risk factors for BCRL occurrence, the determinants of its severity remain underexplored.

METHODS: This retrospective observational study evaluated the risk factors associated with BCRL severity among patients treated at the Motamed Cancer Institute, Tehran, Iran. Female patients with unilateral BCRL aged 25-75 years were included. Data were collected over a 10-year period and analyzed for demographic, clinical, and pathological variables. Lymphedema severity was assessed using established clinical staging criteria and categorized into early-stage (stages 1 and 2a) and advanced-stage (stages 2b and 3) groups. Also, presence of fibrosis and non-pitting edema were other indicators of BCRL severity. Statistical analyses included univariate and multivariate logistic regression to identify predictors of advanced-stage BCRL.

RESULTS: A total of 500 participants were analyzed, with a mean age of 41.16 ± 10.20 years and BMI of 28.72 ± 4.78 kg/m². Advanced-stage BCRL was significantly associated with older age (p = 0.00), higher number of excised lymph nodes (p = 0.04), and radiotherapy (p = 0.00). Multivariate analysis identified radiotherapy as the strongest independent predictor of advanced-stage BCRL (OR: 2.12, 95% CI: 1.22-3.67, p = 0.007). Other variables, including tumor grade, molecular subtypes, and type of surgery, did not independently predict BCRL severity.

CONCLUSION: Advanced-stage BCRL is influenced by multiple factors, particularly radiotherapy and the extent of lymph node dissection. These findings underscore the importance of strategies to mitigate risk among breast cancer survivors, especially those undergoing radiotherapy. Further research is warranted to explore targeted interventions for reducing BCRL severity.

PMID:40394662 | DOI:10.1186/s13014-025-02663-2

Reprod Health. 2025 May 21;22(1):88. doi: 10.1186/s12978-025-02030-0.

ABSTRACT

BACKGROUND: Approximately one in six people is experiencing infertility at some point in their lives. In response, health insurance coverage for infertility treatments has been strengthened. However, studies examining lifestyle factors that affect infertility remain lacking, highlighting the need to generate objective evidence to address infertility issues using national-level datasets.

METHODS: The General Healthcare Screening Program dataset from National Health Insurance Service database was employed in this study to examine infertility and childbirth among women aged 22-49 years. In 2020, 25,333 women with infertility and 73,759 women who had given birth were initially identified. After applying propensity score matching for age, Charlson Comorbidity Index score, and income level, the final study population included 24,325 women with infertility and 24,325 women who with childbirth. Employing a case-control study design, lifestyle factors (drinking, smoking, and physical activity) and health checkup outcomes (underweight, overweight, hypertension, diabetes, kidney function, anemia, and menstrual disorders) were assessed in this study. Statistical analyses included chi-squared tests, t-tests, and logistic regression.

RESULTS: This study revealed significant risk factors for infertility: two high-risk lifestyle factors, including heavy drinking and smoking, and five health conditions, comprising underweight, hypertension, diabetes, kidney function loss, and menstrual disorders. Conversely, being overweight, not engaging in vigorous physical activity, and anemia were negatively associated with infertility.

CONCLUSIONS: These findings underscore the need for lifestyle modifications and personalized preconception care to improve fertility outcomes.

TRIAL REGISTRATION: Not available.

PMID:40394661 | DOI:10.1186/s12978-025-02030-0

Infect Agent Cancer. 2025 May 20;20(1):30. doi: 10.1186/s13027-025-00661-3.

ABSTRACT

PURPOSE: To explore the failure patterns, outcomes, and treatment response of differentiated non-keratinizing nasopharyngeal carcinoma (DNKC) and to further investigate the role of plasma Epstein-Barr virus (EBV)-DNA in follow-up monitoring, prognostic prediction, and assessment of treatment efficacy in DNKC.

METHODS: We retrospectively collected data from patients diagnosed with DNKC from January 2015 to February 2022. The life-table method, Kaplan-Meier survival, and Cox proportional hazards analysis were used for statistical analyses.

RESULTS: A total of 102 patients were included. Of the 77 patients with available EBV-DNA levels, 61 patients (79.2%) had EBV-DNA detectable before treatment. Twenty-seven patients (26.5%) experienced disease recurrence, and 88.9% (24/27) relapsed in the first three years. There were 20 patients who experienced disease recurrence and had pre-treatment EBV-DNA status records. At the time of disease progression, 4 patients initially had undetectable EBV-DNA remained undetectable. Among the 16 patients with initially detectable EBV-DNA, 15 (93.8%) had detectable EBV-DNA. Nodal stage and EBV-DNA levels before treatment were found to be independent prognostic factors for distant metastasis-free survival (DMFS) and disease-free survival (DFS). Those with residual EBV-DNA after induction chemotherapy had significantly inferior DMFS (P = 0.003), DFS (P = 0.006), and overall survival (OS) (P = 0.006) than those without residual EBV-DNA after IC. Those with residual EBV-DNA after radiotherapy had significantly inferior local recurrence-free survival (P = 0.003), DMFS (P < 0.001), DFS (P < 0.001), OS (P < 0.006) than those without residual EBV-DNA after radiotherapy.

CONCLUSION: Our study highlights the aggressive nature of DNKC, characterized by early recurrence. EBV-DNA levels may serve as a biomarker to monitor treatment response, prognostic prediction, and recurrence surveillance.

PMID:40394615 | DOI:10.1186/s13027-025-00661-3

Reprod Health. 2025 May 20;22(1):86. doi: 10.1186/s12978-025-02016-y.

ABSTRACT

BACKGROUND: Polycystic ovary syndrome (PCOS) is a chronic, multifaceted condition influenced by epigenetic and environmental factors that is responsible for a significant proportion of anovulatory infertility cases. Here, we analyzed the global, regional, and national burdens of PCOS from 1990 to 2021 using data from the Global Burden of Disease 2021 (GBD 2021).

METHODS: Incidence, prevalence, and Disability-Adjusted Life Years (DALYs) data relevant to PCOS from 204 countries and 21 territories from 1990 to 2021 were obtained from the GBD 2021 study. Here, we considered age-standardized rates (per 100,000 individuals) with 95% uncertainty intervals (95% UIs) obtained from the aforementioned research and presented trends based on age and Socio-demographic Index (SDI) parameters.

RESULTS: In 2021, the global age-standardized incidence and prevalence rates of PCOS were 30.7 per 100,000 and 867.7 per 100,000, respectively, representing an increase of 26.77% and 28.21% since 1990. Additionally, age-standardized disability-adjusted life years stood at 7.6 per 100,000 globally in 2021, marking a 27.58% increase from 1990. Age-standardized prevalence of PCOS varied across countries, ranging from 93.1 to 3978.9 cases per 100,000 women, with Italy (3978.9), Japan (3104.7), and New Zealand (2789.7) having the highest rates. Notably, PCOS prevalence was noted to peak globally among females 15-19 years of age. Regions with a high SDI exhibited the highest age-standardized incidence (70.2), prevalence (1720.7), and DALY (15.2) rates of PCOS. Furthermore, a nonlinear correlation between PCOS burden and SDI was noted, with prevalence rates peaking around an SDI of approximately 0.9.

CONCLUSION: Our findings highlight the growing global impact of PCOS and underscore the need for concerted efforts to attenuate the increasing global prevalence of this condition. Significantly divergent PCOS disease burdens were observed across different age groups and SDI regions, with high SDI regions bearing heavier burdens. The increased disease burden among younger age groups and regional disparities underscore urgency for targeted intervention and formulation of policies to effectively address this public health issue.

PMID:40394609 | DOI:10.1186/s12978-025-02016-y