Nevin Manimala

Discov Oncol. 2025 Nov 28. doi: 10.1007/s12672-025-04172-w. Online ahead of print.

ABSTRACT

BACKGROUND: The current understanding of the relationship between circulating metabolites and neuroblastoma (NB) risk is insufficient. Herein, bidirectional Mendelian randomization (MR) studies were utilized to examine the potential causal associations of metabolites and the risk of NB.

METHODS: Significant single-nucleotide polymorphisms (SNPs) associated with circulating metabolites were obtained from the genome-wide association study (GWAS) in the European population (N = 7824). Summary statistics for NB were aggregated from prior GWAS studies encompassing 1,627 patients and 3,254 cancer-free children. The causality was assessed primarily by inverse-variance weighted (IVW), along with MR-Egger regression, weighted median estimator, and weighted mode method.

RESULTS: Among the 486 metabolites analyzed, a genetically determined elevation in blood butyrylcarnitine concentration (log₁₀) was significantly correlated with a 51.5% decrease in NB risk [IVW odds ratio (OR) = 0.485, 95% confidence interval (CI): 0.285-0.826, P = 0.008]. In the reverse MR analyses, an increase in log odds of NB risk demonstrated a significant correlation with a decrease in guanosine [IVW Beta ± SE: -0.042 ± 0.015 log₁₀ change, P = 0.004] and an elevation in 3-methyl-2-oxobutyrate [IVW Beta ± SE: 0.010 ± 0.004 log₁₀ change, P = 0.011] levels. Besides, no significant causal effect of NB on butyrylcarnitine was observed.

CONCLUSIONS: This research identifies bidirectional causal relationships between circulating metabolites and NB. Increased levels of blood butyrylcarnitine are associated with a reduced risk of NB, whereas lower levels of guanosine and higher levels of 3-methyl-2-oxobutyrate are indicative of NB patients. Further investigation is required for the mechanisms.

PMID:41313542 | DOI:10.1007/s12672-025-04172-w

J Endocrinol Invest. 2025 Nov 28. doi: 10.1007/s40618-025-02770-7. Online ahead of print.

ABSTRACT

BACKGROUND: Endothelial dysfunction may contribute to the increased cardiovascular risk associated with thyroid diseases. This systematic review and meta-analysis aimed to assess endothelial function, evaluated by flow-mediated dilation (FMD), in both hypo and hyperthyroidism, and its response to treatment.

METHODS: We searched Embase and PubMed (until April 2025) for studies on FMD in hypo- and hyperthyroidism (PROSPERO registration number: CRD42024629806). Risk of bias was assessed using Cochrane criteria. Mean differences (MD) with 95% confidence intervals (CI) were calculated using random-effects models. Statistical heterogeneity was assessed with I² statistics. Analyses were conducted using Review Manager 5.4.1.

RESULTS: Forty-two studies (1,663 subjects with hypothyroidism, 247 with thyrotoxicosis/endogenous hyperthyroidism, and 1520 euthyroid controls) were included. FMD was significantly reduced in subjects with untreated hypothyroidism compared to euthyroid controls (MD -2.99, 95% CI, -3.83, -2.14; I² = 99%), improved with levothyroxine treatment (MD 3.06, 95% CI: 1.94, 4.19; I² = 91%) and reached values similar to controls upon restoration of euthyroidism (MD 0.22, 95% CI: -0.75, 1.18; I² = 75%). A non-statistically significant difference emerged comparing untreated hyperthyroid subjects with controls (MD – 2.55; 95% CI: -5.38, 0.28; I² = 98%), and low risk of bias studies showed reduced FMD in this subset (MD – 6.57; 95% CI: -7.53, – 5.60; I² = 45%). Subclinical hyperthyroidism was associated with FMD impairment (MD – 4.21; 95% CI: -7.07, – 1.35; I² = 97%).

CONCLUSION: Hypothyroidism is associated with endothelial impairment, reversible after restoration of euthyroidism, highlighting the importance of appropriate management. Hyperthyroidism, especially subclinical, seems associated with FMD reduction, but larger, well-designed studies are needed.

PMID:41313532 | DOI:10.1007/s40618-025-02770-7

Environ Sci Pollut Res Int. 2025 Nov 28. doi: 10.1007/s11356-025-37176-8. Online ahead of print.

ABSTRACT

Anaerobic digestion is an effective technology for converting organic waste into biogas while reducing environmental pollution. This study investigates the impact of co-digesting waste-activated sludge (WAS) with wheat straw, rice straw, and bokashi on biogas production. Nine anaerobic batch reactors were operated under mesophilic conditions (35 °C), incorporating different proportions of bokashi (1% and 2%) along with rice and wheat straw (4%). The results revealed that reactors supplemented with wheat and rice straw exhibited higher biogas production than the control reactor (sludge only). Wheat straw outperformed rice straw in improving biogas yield, total solids (TS) reduction, total volatile solids (TVS) degradation, and chemical oxygen demand (COD) removal. The addition of bokashi enhanced biogas production, confirming its role in accelerating organic matter breakdown. The maximum biogas yield was observed in the reactor containing sludge co-digested with wheat straw and 2% bokashi, which generated three times more biogas than the control. This reactor also exhibited the highest degradation rates of TS (57.83%), TVS (66.37%), and COD (71.53%). Furthermore, pH remained stable within the optimal range across all reactors, ensuring a balanced digestion process. Statistical analysis revealed significant correlations between organic matter degradation (COD, TS, TVS reduction) and biogas production, demonstrating that effective substrate decomposition improves biogas yield. The recurrent neural network (RNN) model was applied to experimental data to predict biogas production. With an exceptionally low root mean square error (RMSE) of 0.0041, R² close to 1, and MAE 0.0117, the model exhibited excellent accuracy and reliability in generating precise predictions.

PMID:41313517 | DOI:10.1007/s11356-025-37176-8

Dan Med J. 2025 Nov 12;72(12):A04250344. doi: 10.61409/A04250344.

ABSTRACT

INTRODUCTION: Since 2022, Denmark has received approx. 50,000 Ukrainian refugees. We examined the sociodemographic characteristics, disease patterns and associated risk factors of Ukrainian refugees receiving a general health assessment (GHA) at the Migrant Health Outpatient Clinic, Hvidovre Hospital.

METHODS: This cross-sectional study based on a prospective inclusion of patients, included all Ukrainian adults assessed between April 2022 and December 2024. The GHAs included blood samples (biochemistry and screening for infectious diseases), a questionnaire, a medical interview and a physical examination. Data were analysed using descriptive and inferential statistics.

RESULTS: A total of 101 participants were included. Common findings were poor oral health (44%) and PTSD symptoms (22%). Screening for infectious diseases revealed previous hepatitis B infection (15%), tuberculosis infection (12%) and HIV infection (4%). COVID-19 vaccine adherence was low (50%). We also found that exposure to war trauma was associated with PTSD symptoms.

CONCLUSIONS: The study population had a significant burden of mental and physical health problems and indications of low vaccine coverage, highlighting the need for increased awareness of the health needs of Ukrainian refugees in Denmark and the importance of providing GHAs to at-risk individuals.

FUNDING: None.

TRIAL REGISTRATION: Ethical approval was granted by the Team for Medical Records Data, Capital Region of Denmark.

PMID:41312704 | DOI:10.61409/A04250344

Int J Technol Assess Health Care. 2025 Nov 28;41(1):e81. doi: 10.1017/S026646232510322X.

ABSTRACT

INTRODUCTION: The simultaneous existence of low-value health care and underutilization of high-value care are global problems. Health technology reassessment (HTR) aims to optimize the value for money of technologies already in use within health care. Identifying candidate interventions for HTR remains challenging. Therefore, we tested a novel method to identify candidate outpatient prescription drugs for HTR through practice variation.

METHODS: We used administrative data for all publicly funded outpatient prescriptions dispensed to persons aged 65 or older in Alberta in 2023. Through quantitative comparison of funnel plots for Anatomic Therapeutic Chemical (ATC) classes at the fourth level stratified by prescriber specialty, variation in prescription dispensation rates between prescribers was used to estimate three outcomes: the number of prescribers affected, the number of patients affected, and the potential budgetary impact. We ranked combinations of ATC class and prescriber specialty in descending order for each outcome, with use above and below the mean considered separately.

RESULTS: We analyzed data on 17.5 million dispensations, encompassing more than 8,000 prescribers and approximately 600,000 patients. The top ATC class-prescriber specialty combinations for each outcome showed high similarity above and below control limits while exhibiting minimal overlap between outcomes.

CONCLUSIONS: Our method successfully identified ATC class-prescriber specialty combinations with marked variation in use, for potential advancement through the HTR process. Depending on the perspective of those undertaking HTR of prescription drugs, different outcomes may be useful in technology prioritization. To make the ATC class-prescriber specialty combinations actionable, future efforts should focus on exploring the patients affected.

PMID:41312685 | DOI:10.1017/S026646232510322X

Arthritis Care Res (Hoboken). 2025 Nov 28. doi: 10.1002/acr.70005. Online ahead of print.

ABSTRACT

OBJECTIVE: The goal was to assess the diagnostic performance of three novel autoantibodies (NA) for Sjögren’s disease (SjD) by comparing NA prevalence in patients with SjD, other autoimmune rheumatic diseases (ARDs), nonspecific chronic sialadenitis (CS), and controls.

METHODS: We identified rheumatology outpatients with confirmed SjD, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), CS, and healthy controls. Subjects underwent serum testing for antibodies to salivary gland protein 1 (SP-1), parotid secretory protein (PSP) and carbonic anhydrase-6 (CA-6). Subjects with SjD, CS and controls also underwent testing of saliva. Receiver operating characteristic (ROC) curve C-statistics along with sensitivity, specificity, positive and negative likelihood ratios were calculated for each serum autoantibody for SjD vs. CS or controls.

RESULTS: Among 468 patients screened, 444 were analyzed including cohorts with: SjD (n=149), SLE (n=70), SSc (n=56), RA (n=73), CS (n=31) and controls (n=65). There was no statistical difference (p=0.80) in the presence of one or more NA in the serum of SjD patients compared to subjects with other ARDs, CS, or controls. ROC curves demonstrated poor discriminative ability for SjD versus CS or controls for any positive NA (0.47) or any individual NA (range 0.44 to 0.53). The positive likelihood ratio for having any positive novel autoantibody was 1.04 and 0.83 for SjD vs. CS or controls, respectively.

CONCLUSION: Testing serum for NA demonstrated poor ability to distinguish patients with SjD from control patients or those with CS or other ARDs. This serum autoantibody panel is not likely to be useful as a diagnostic test for SjD.

PMID:41312674 | DOI:10.1002/acr.70005

Arthritis Care Res (Hoboken). 2025 Nov 28. doi: 10.1002/acr.70002. Online ahead of print.

ABSTRACT

OBJECTIVE: Telehealth and shared decision-making (SDM) enhance the care of people with rheumatic diseases. Responding to calls for training on telehealth and SDM, we developed an educational intervention for rheumatology fellows-in-training (FITs).

METHODS: FITs conducted two patient care telehealth encounters (pre- and post-intervention). Following the first encounter, FITs completed an online module highlighting the nuances of SDM during telehealth and a simulated patient encounter to practice telehealth skills, especially SDM. After each observation, FITs received feedback on their “webside” manner, SDM, and visit coordination skills via feedback forms (FF). Wilcoxon-signed rank tests compared quantitative FF measures, while qualitative methods analyzed written comments. FITs completed a survey and self-reported their confidence in SDM during telehealth visits.

RESULTS: Nine and eleven FITs completed pre- and post-intervention encounters, respectively; Forty-seven FITs completed the simulation. Total points earned on the FF and points specific to the visit coordination subsection of the FF significantly increased from pre- to post-intervention (p=0.011 and p=0.049, respectively). “Webside” manner scores improved without reaching statistical significance (p=0.067). SDM scores remained unchanged, while confidence conducting SDM during telehealth improved significantly (p < 0.001). Qualitative analysis highlighted the apt use of technology as a skill FITs could further develop for enhancing SDM during telehealth.

CONCLUSIONS: Education dedicated to telehealth skills with an emphasis on SDM improves FITs’ confidence in practicing SDM during telehealth and advances general telehealth skills implemented during patient care. Our materials and approach to instruction prepare FITs for delivering telehealth care and enriching patient-centeredness as new entrants into the rheumatology workforce.

PMID:41312639 | DOI:10.1002/acr.70002

Disaster Med Public Health Prep. 2025 Nov 28;19:e317. doi: 10.1017/dmp.2025.10227.

ABSTRACT

AIM: To assess the iodine status of pregnant women from disadvantaged groups in Kahramanmaraş Province 1 year after the earthquake, including factors affecting iodine status.

METHODS: 510 healthy pregnant women were included in the study. A questionnaire was given to pregnant women after the earthquake to assess changes in diet and other social factors. Thyroid function, autoantibodies, thyroglobulin, urinary iodine concentration (UIC), creatinine (Cr) levels, and ultrasound were measured. Thyroid ultrasound was also performed to assess thyroid volume.

RESULTS: The median UIC of the participants was 91.27 μg/g Cr (Q1-Q3 = 62.53-142.86). The rate of low iodine status (<150 μg/g Cr) was 77.3% and the incidence of goiter was 19.2%. After the earthquake, 69% of pregnant women lived in urban areas and 31% in rural areas. 11.8% of the areas where they lived were moderately damaged, 11.4% severely damaged, and 5.9% completely destroyed. 15.1% were still living in temporary shelters 1 year after the earthquake. The risk of low UIC was 2.2 times higher for those living in temporary shelters after the earthquake.

CONCLUSIONS: Temporary shelters after the earthquake were the main risk factor for low iodine status. We need to support these groups after disasters and reduce the number of people living in temporary shelters.

PMID:41312633 | DOI:10.1017/dmp.2025.10227

J Gynecol Oncol. 2025 Nov 17. doi: 10.3802/jgo.2026.37.e34. Online ahead of print.

ABSTRACT

OBJECTIVE: Cervical intraepithelial neoplasia (CIN) grades 2 and 3 are precancerous lesions requiring timely treatment to prevent progression to invasive cancer. While conization is the standard therapy, it may negatively impact future fertility. This study evaluated the therapeutic efficacy of cervical laser vaporization compared with laser conization.

METHODS: This retrospective study included patients with CIN2-3 who underwent laser vaporization or conization at NTT East Sapporo Medical Center between January 2018 and December 2022. Treatment selection was based on colposcopic findings, lesion grade, age, and fertility desire. Human papillomavirus (HPV) testing and cytology were performed before treatment and at 3 months postoperatively. Cytologic follow-up continued biannually for 2 years. The primary outcome was absence of cytologic abnormalities throughout the follow-up period. Patients lost to follow-up were excluded. Fisher’s exact test was used for statistical comparisons.

RESULTS: Of 319 patients (93 conization; 226 vaporization), the mean age was 41 in the conization group and 33 in the vaporization group. Despite the age difference, no significant differences were observed in 2-year cytologic cure rates or 3-month HPV clearance in CIN3 cases. HPV16 was the most common genotype, followed by HPV52 and HPV58.

CONCLUSION: A Laser vaporization showed comparable efficacy to conization in appropriately selected CIN2-3 cases. It may be a fertility-preserving option for younger patients. Strengthening HPV vaccination programs remains essential for reducing high-risk HPV infections.

PMID:41312632 | DOI:10.3802/jgo.2026.37.e34

Pharm Stat. 2026 Jan-Feb;25(1):e70058. doi: 10.1002/pst.70058.

ABSTRACT

Cancer immunotherapy trials often present unique challenges for time-to-event data modeling and analysis due to heterogeneous treatment effects across time or subgroups. A few known scenarios are delayed treatment effects and cure rates, where survival and hazard functions often take complex shapes. Sophisticated survival models like piecewise model are commonly used to capture the shapes of the functions. However, the time of hazard transition for individual patients varies, making it necessary to model it as a latent random variable. In this study, we propose a smoothed piecewise model to account for the random hazard transition time, based on the linear relationship between hazard function and the distribution function of the individual transition time within the smoothing window. We then develop the weighted geometric average hazard ratio (wgAHR) to estimate sample size and power based on the non-centrality parameter of the weighted log-rank statistics under non-proportional hazard (non-PH). We demonstrate that the wgAHR is not only directly linked to the sample size formula, but can also be interpreted as a measure of treatment effect, even when the proportional hazard assumption is violated. Additionally, we provide maxCombo, a combination of weighted log-rank statistics, for robust testing across different non-proportional hazard scenarios. Simulation studies and real trial examples illustrate the performance and robustness of the wgAHR based method in power and sample size estimation in cancer immunotherapy trials.

PMID:41312579 | DOI:10.1002/pst.70058