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Role of vitamin D supplementation and vitamin D receptor in drug-resistant epilepsy: A double-blind placebo-controlled trial conducted in India

Epilepsia. 2025 Jun 14. doi: 10.1111/epi.18492. Online ahead of print.

ABSTRACT

OBJECTIVE: Vitamin D has demonstrated potential anticonvulsant effects in experimental and pilot clinical studies; the results of these remain inconclusive. This study aims to investigate the efficacy and safety of adjunctive Vitamin D supplementation in reducing seizure frequency, modulating vitamin D receptor (VDR) activity, and altering the putative biomarkers of epileptogenesis in persons with drug-resistant epilepsy (DRE).

METHODS: This double-blind, placebo-controlled, parallel-group, adjunctive trial recruited patients from a tertiary care hospital in India. Adult persons with DRE and serum Vitamin D levels <30 ng/mL, experiencing ≥2 seizures/month, were randomized (1:1 ratio) to receive either Vitamin D (60,000 IU/week for 3 months, followed by 60 000 IU/month for the next 3 months) or a matching placebo, in addition to their ongoing antiseizure medications. The primary outcome was the percentage change in monthly seizure frequency from baseline to 6 months. Secondary outcomes included 50% responder, serum Vitamin D (25-hydroxycholecalciferol) levels, VDR protein/mRNA expression, putative biomarkers of epileptogenesis (including high-mobility group box protein 1 [HMGB1] and neurotrophin-3 [NT-3]), quality of life, and safety assessment.

RESULTS: Of 200 participants, 99 were in the Vitamin D group and 101 were in the placebo group. No statistically significant difference was observed between the Vitamin D and placebo groups in the primary outcome of percentage change in monthly seizure frequency from baseline after 6 months of intervention (median 33.3, interquartile range [IQR] 0-57.4 vs 16.7, 0-66.7; median estimate 5.5, 95% confidence interval [CI]: -6.7 to 19.2); p = 0.36]. The 50% responder rate was similar between groups (37% vs 35%; odds ratio 1.1, 95% CI: 0.6-1.9; p = 0.68). However, Vitamin D supplementation significantly increased VDR mRNA and protein expression (p < 0.001) and decreased HMGB1 (p = 0.001) and NT-3 (p = 0.002) levels compared to placebo. The recommended serum Vitamin D level (≥30 ng/mL) was achieved in only 36% of subjects in the Vitamin D group. Safety outcomes were comparable between groups.

SIGNIFICANCE: Six months of Vitamin D supplementation at the selected dose did not significantly reduce seizures compared to placebo, potentially due to few persons with DRE achieving recommended serum Vitamin D level (≥30 ng/mL). Significant upregulation of VDR expression and reduction in putative biomarkers of epileptogenesis following Vitamin D supplementation were seen in Vitamin D group despite no corresponding decrease in seizure frequency. This suggests that Vitamin D may have underlying therapeutic effects that warrant further investigation and clinical correlation.

PMID:40516032 | DOI:10.1111/epi.18492

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How am I Going to Live? How am I Going to Pay Rent?”: A Mixed Methods Investigation of Employment, Stigma, and Financial Hardship Among LGBTQ+ Cancer Caregivers

Cancer Control. 2025 Jan-Dec;32:10732748251351105. doi: 10.1177/10732748251351105. Epub 2025 Jun 14.

ABSTRACT

IntroductionEmployment changes among cancer caregivers are common and can result in financial hardship. Lesbian, gay, bisexual, transgender, queer, and other identities outside of cisgender heterosexual (LGBTQ+) individuals are more likely to live in poverty and experience workplace discrimination than non-LGBTQ+ individuals. This study aimed to assess the impact of caregiving-related employment changes and anti-LGBTQ+ stigma on financial hardship and describe lived experiences with financial hardship and related employment changes among LGBTQ+ cancer caregivers.MethodsAn explanatory mixed-methods study was conducted and included a national survey and individual interviews with survey participants. Multivariable logistic regression models were used to test the association of employment changes with financial hardship. An inductive qualitative analysis guided by two of the three domains of financial hardship (ie, material and behavioral) was conducted. Quantitative and qualitative data were integrated throughout the study.ResultsA total of N = 332 LGBTQ+ cancer caregivers participated in the survey, and N = 14 participated in an interview. The average modified COmprehensive Score for financial Toxicity and Caregiver Reaction Assessment financial sub-scale were 25.6 (SD: 9.9, Range: 1-44) and 2.99 (SD: 1.0, Range: 1-5). Employment changes (OR: 3.32, 95% CI: 1.73-6.36) and anti-LGBTQ+ stigma (OR: 2.21, 95% CI: 1.47-3.32) were associated with high financial hardship. Three overarching themes from the qualitative analysis included: 1) Financial Hardship: Increased Costs, Strained Finances, and Lost Wages; 2) Caregiving as an LGBTQ+ Person: Stigma, Outness, and Expectations; and 3) Financial Unmet needs and Recommendations.ConclusionLGBTQ+ cancer caregivers experience substantial financial hardship that is associated with employment changes and anti-LGBTQ+ stigma. LGBTQ + cancer caregivers reported varying levels of outness and acceptance that directly influenced their access to financial support. Cancer-related financial hardship interventions tailored to the needs of LGBTQ+ individuals are needed.

PMID:40516028 | DOI:10.1177/10732748251351105

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Cumulative live birth rates among over 13,000 poor ovarian responders from 2015 to 2023: a retrospective cohort study assessing the efficacy of natural cycle and controlled ovarian stimulation

J Assist Reprod Genet. 2025 Jun 14. doi: 10.1007/s10815-025-03544-z. Online ahead of print.

ABSTRACT

BACKGROUND: Natural cycle in vitro fertilization (NC-IVF) represents a convenient and safe assisted reproductive technology, making it particularly advantageous for patients with poor ovarian response (POR). This research evaluates the effectiveness of NC-IVF for women with POR, aiming to inform personalized treatment decisions.

METHOD: This retrospective cohort study encompassed 13,013 cycles involving women diagnosed with poor ovarian response according to the Bologna criteria. These patients underwent either natural cycles or controlled ovarian stimulation cycles. The primary outcome measure was the cumulative live birth rates, and the secondary outcomes included laboratory and clinical outcomes.

RESULTS: A total of 1073 natural cycles and 11,940 COS cycles were analyzed, with 5956 undergoing low-dose gonadotropin treatment and 5984 receiving high-dose gonadotropin. The basic characteristics were comparable among the three groups. In both fresh and frozen embryo transfer cycles, clinical pregnancy rates, implantation rates, and live birth rates were comparable across all three groups. Furthermore, no statistically significant differences were observed in cumulative live birth rates or time to first live birth between the groups examined. Expenditures in the natural cycle group were substantially lower than those in both COS cohorts. Importantly, further analysis indicated that there were no significant differences among the three groups concerning either pregnancy complications or neonatal outcomes.

CONCLUSION: Our findings indicate that for women demonstrating a poor ovarian response, NC treatment yields comparable pregnancy and live birth rates when compared to controlled ovarian stimulation methods. The natural cycle represents a safe, effective, and economically viable treatment option for this patient population.

PMID:40516010 | DOI:10.1007/s10815-025-03544-z

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The role of activated partial thromboplastin time-clot waveform analysis in distinguishing positive samples of lupus anticoagulant from hemophilia A

J Thromb Thrombolysis. 2025 Jun 14. doi: 10.1007/s11239-025-03128-9. Online ahead of print.

ABSTRACT

INTRODUCTION: Clot waveform analysis (CWA) is a technique that continuously monitors changes in light transmittance or absorbance during fibrin clot formation in plasma, enhancing routine clotting test assessment. Patients with Lupus Anticoagulant (LA) and Hemophilia A (HA) both exhibit isolated prolongation of activated partial thromboplastin time (aPTT); however, their management differs significantly. CWA can aid in distinguishing between these conditions, particularly in cases where standard coagulation tests are inconclusive and specialized assays are unavailable.

METHODS: This prospective case-control study included patients with demonstrable LA (n = 69), healthy controls (n = 75) and diseased controls [HA with (n = 16) and without inhibitor (n = 36).

RESULTS: The quantitative data of aPTT-CWA including velocity peak time, acceleration peak time and height of acceleration [-] were significantly lower in LA-positive samples with prolonged aPTT in comparison with HA without inhibitors. The qualitative data comprising Shoulder in 1st derivative, Biphasic wave in 2nd derivative [-] and Serrated wave pattern in 2nd derivative were significantly common in HA samples without inhibitors. In comparison to healthy controls, LA-positive patients with normal aPTT had significantly lower velocity peak time and height of velocity along with higher width of velocity. In acceleration peak time and width of acceleration [-] peak were significantly higher along with lower height of acceleration [+] and height of acceleration [-]. AUROCs of height of acceleration [-], width of acceleration [-] and width of velocity were statistically and biologically significant. The shoulder in 2nd derivative was significantly common in LA-positive samples.

CONCLUSION: The aPTT-CWA has limited utility for differentiating LA positive from HA samples with and without inhibitors. However, aPTT-CWA may help in selecting patients with normal aPTT who merit further confirmatory testing for LA with a compatible history.

PMID:40515980 | DOI:10.1007/s11239-025-03128-9

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Utility of multiparametric MRI including T1/T2 mapping and IVIM/diffusion imaging for the evaluation of non-obstructive azoospermia

MAGMA. 2025 Jun 14. doi: 10.1007/s10334-025-01267-x. Online ahead of print.

ABSTRACT

INTRODUCTION AND OBJECTIVES: The management of non-obstructive azoospermia (NOA) remains challenging because no predictive test for the presence of localized spermatogenesis exists. Previous work considered MRI techniques, such as spectroscopy (MRS) and diffusion weighted imaging (DWI), in this role. We report here data from a prospective study evaluating additional advanced MRI sequences for predicting spermatogenesis in patients with NOA.

METHODS: 9 fertile volunteers and 18 men with NOA were prospectively recruited. Each participant underwent a novel multi-parametric MRI consisting of T1 and T2 mapping as well as intravoxel incoherent motion (IVIM) and diffusion weighted imaging (DWI). A single radiologist drew representative regions of interest on the best quality images for each sequence and recorded the mean values. Sperm extraction procedure results were recorded. Two-end points were evaluated: NOA versus fertile controls and the presence of viable sperm within the NOA cohort. The data were analyzed per patient. Nonparametric and logistic regression statistical analysis were used.

RESULTS: 9 fertile men (median 43 years old, 2 children) and 18 men with NOA (median 37 years old, 0 children) were studied. 11 of the 18 men with NOA had testicle sampling. 4 men with NOA had viable sperm. Follicle-stimulating hormone and testosterone levels were not significantly different among NOAmen with and without sperm (p-value = 0.58 and 0.25). Nonparametric analysis with the Wilcoxon rank sum test showed T2 relaxation time was lower among NOA patients (median 101 vs 135 ms, p-value = 0.002), apparent diffusion coefficient (ADC) was higher among NOA patients (median 127.9 vs. 106.7 × 10-5 mm2/sec, p-value = 0.005). T1 relaxation time, alpha (Water diffusion heterogeneity index), D (IVIM-based apparent diffusion coefficient), DDC (Distributed diffusion coefficient) and D* (pseudodiffusion) were also significantly different. On logistic regression analysis, both T2 and ADC were associated with NOA; The odds of NOA decreased by 6% for each msec increase in T2 (p-value = 0.02) while the odds of NOA increased by 11% for each 10⁻5 mm2/sec increase in ADC, (p-value = 0.02). T2 yielded a larger area under the receiver operating characteristic curve than ADC (0.87 versus 0.84). Alpha, D, DDC and D* also predicted NOA. Amongst men with NOA who underwent testicle sampling, T2 was lower in testicles of patients with no sperm retrieved (median 73 vs 134. msec, p-value = 0.02). The remaining variables were not significantly different between the cohorts.

CONCLUSIONS: In spite of the small sample size, particularly for men with NOA who underwent sperm extraction, these results suggest that several novel MRI parameters, such as T2 relaxation time and certain IVIM/DWI parameters, are able to distinguish between fertile men and men with NOA as well as potentially predict successful sperm extraction in men with NOA. Additional larger prospective studies of men with NOA undergoing sperm extraction are warranted.

PMID:40515974 | DOI:10.1007/s10334-025-01267-x

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Analysis of the characteristics of the fish community structure and aquaculture capacity in the medium-sized reservoir-take the Qiaoying Reservoir as the case, China

Environ Monit Assess. 2025 Jun 14;197(7):751. doi: 10.1007/s10661-025-14205-0.

ABSTRACT

This study investigates the ecological dynamics of Qiaoying Reservoir, a medium-sized multi-purpose water body in Zhejiang Province, China, through seasonal (spring and autumn 2022) analyses of aquatic communities, water quality, and Ecopath modeling. Fish community structure showed seasonal shifts, with Cypriniformes dominating (68.75% in spring, 88.89% in autumn), while zooplankton composition transitioned from Cladocera-dominated (38.46%) to Copepoda-dominated (35.71%) between seasons. Phytoplankton biomass and density exhibited consistent spatial patterns (higher in southeastern zones). Water quality met Class I standards, with stable physicochemical parameters. Ecopath modeling revealed simplified trophic interactions (Connectance Index, 0.333; Omnivory Index, 0.136), with 76% of energy flow concentrated at trophic level I (primary producers). The low inter-trophic transfer efficiency (total 2.25%) highlighted imbalances, notably insufficient grazer pressure on phytoplankton. Recommendations include diversifying fish stocking (Hypophthalmichthys nobilis, Cyprinus carpio, Hypophthalmichthys molitrix, Carassius auratus, and Megalobrama terminalis) to enhance trophic regulation, adjusting harvest strategies. This integrated approach supports sustainable fisheries management by aligning ecological capacity with socioeconomic needs, emphasizing the role of filter-feeding species in maintaining water quality and ecosystem stability.

PMID:40515961 | DOI:10.1007/s10661-025-14205-0

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Prevalence and clinical significance of autoantibodies to sulphite oxidase and glycogen phosphorylase in Chinese primary biliary cholangitis patients

Mol Biol Rep. 2025 Jun 14;52(1):593. doi: 10.1007/s11033-025-10646-5.

ABSTRACT

OBJECTIVE: To evaluate the prevalence and clinical significance of autoantibodies to mitochondrial sulphite oxidase (SUOX) and glycogen phosphorylase (PYGL) in Chinese PBC patients.

METHODS: Enzyme-linked immunosorbent assays (ELISA) were developed with purified SUOX and PYGL proteins. Serum samples from 780 PBC patients and 352 healthy controls were used for antibody detection. Statistical analysis was performed with antibody results and biochemical data from PBC patients.

RESULTS: Antibodies to SUOX and PYGL were found in 14.23% and 22.94% of PBC patients, but also in 6.53% and 9.37% of healthy controls. There is a significant positive correlation between anti-SUOX and -PYGL with anti-M2, -sp100 and -gp210. Anti-SUOX and -PYGL positivity does not correlate with ursodeoxycholic acid (UDCA) response. Time course analysis found no specific change of anti-SUOX or -PYGL antibody titers in positive patients before and after UDCA treatment.

CONCLUSIONS: The data concluded that anti-SUOX and -PYGL autoantibodies are not serological markers in PBC diagnosis due to a lack of sensitivity and specificity. With the existence of PBC specific autoantibodies in PBC diagnosis and treatment, anti-SUOX and -PYGL status in PBC patients have no significant value.

PMID:40515960 | DOI:10.1007/s11033-025-10646-5

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AI-driven techniques for detection and mitigation of SARS-CoV-2 spread: a review, taxonomy, and trends

Clin Exp Med. 2025 Jun 14;25(1):204. doi: 10.1007/s10238-025-01753-5.

ABSTRACT

The SARS-CoV-2 RNA virus, with its rapid spread and frequent genetic changes, has posed unparalleled obstacles for public health and treatment efforts. Early diagnosis of the disease and the development of effective treatment strategies are the main pillars of epidemic control. In this regard, machine learning (ML) methods, an advanced subset of artificial intelligence (AI), can play an effective role in improving the accuracy of diagnosis and the effectiveness of treatments related to SARS-CoV-2. However, the implementation of ML in clinical settings faces issues such as data heterogeneity, lack of training data, model interpretability challenges, patient privacy protection, and implementation limitations. This article provides a systematic review of the applications of federated learning (FL), deep learning (DL), reinforcement learning (RL), and hybrid approaches in the field of SARS-CoV-2 diagnosis and treatment. Based on the analysis of the results, the main focus of the research was on increasing privacy and security (P&S) with a share of 26%, improving detection accuracy and robustness (DAR) with 24%, and improving computational and communication efficiency (CCE) with 20%. These statistics indicate the importance of prioritizing patient information confidentiality and improving systems’ accuracy and stability against data variability. In conclusion, the findings of this review can pave the way for the practical application of ML technologies in clinical decision-making and improving the quality of healthcare services related to SARS-CoV-2.

PMID:40515956 | DOI:10.1007/s10238-025-01753-5

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Utilization of complementary, alternative, and integrative medicine practices among US adults with and without a diagnosis of cancer

Support Care Cancer. 2025 Jun 14;33(7):582. doi: 10.1007/s00520-025-09627-y.

ABSTRACT

PURPOSE: The purpose of this study was to compare the utilization of complementary, alternative, and integrative medicine (CAIM) therapies between US adults with and without cancer.

METHODS: This investigation is based on publicly available data from the 2022 National Health Information Survey (NHIS). Descriptive statistics are presented for demographic characteristics, physical and mental health factors, and CAIM practices stratified by cancer status. Differences between groups were assessed using chi-squared tests, with significance defined by p < 0.05.

RESULTS: The study included 24,184 individuals without cancer and 3430 individuals with a self-reported history of any cancer type. The majority of participants were of non-Hispanic White racial-ethnic background, 54% were female, and those with cancer were found to be significantly older than those without. Approximately 18% of adults reported meditating during the past 12 months, and 15% practiced yoga; however, individuals with a history of cancer were significantly less likely to practice yoga than non-cases (p < 0.001). While cancer cases sought out practices for pain relief more frequently than non-cases, the utilization of these activities was < 5%.

CONCLUSIONS: Notably, fewer than 20% of US adults who completed the NHIS 2022 survey, regardless of cancer status, reported participating in CAIM practices within the prior year. While some may not find CAIM therapies beneficial or of interest, providing education to this population has the potential to better aid with symptom management. Future research should explore influencing factors for the adoption of these practices to quantify the impact of these modalities and uncover the potential epigenetic changes and biological mechanisms responsible for their effects, particularly among those diagnosed with cancer.

PMID:40515954 | DOI:10.1007/s00520-025-09627-y

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Translating advocacy into action: exploring oncology healthcare professionals’ awareness and use of the Clinical Oncology Society of Australia position statement on exercise in cancer care

Support Care Cancer. 2025 Jun 14;33(7):581. doi: 10.1007/s00520-025-09633-0.

ABSTRACT

PURPOSE: The Clinical Oncology Society of Australia (COSA) position statement on exercise in cancer care encourages all healthcare professionals to discuss, recommend, and refer people with cancer to exercise; however, use of these recommendations in practice is unknown.

METHODS: Oncology healthcare professionals working in Australia were invited to complete a cross-sectional online survey that assessed contextual factors that influence implementation of COSA exercise guidance in cancer care, based on the Consolidated Framework for Implementation Research.

RESULTS: We received 133 survey responses. Most were women (74%), nurses (35%), or oncologists (26%), involved in cancer care for > 10 years (63%), and in a public hospital setting (69%). Most participants agreed that exercise is beneficial (94%) and the COSA recommendations would positively influence patients’ exercise behaviours (94%). However, only 35% routinely apply COSA recommendations in practice, and only 35% believe they are the best person to provide exercise support. Patient-level barriers included needing additional support to access exercise (92%), most commonly financial (74%). Organisational-level barriers included a lack of dedicated resources to support delivering exercise guidance (69%), and not believing providing exercise guidance is an important part of their role (51%). Only 24% agreed their organisation revised practice based on the COSA recommendations.

CONCLUSION: Despite most oncology healthcare professionals agreeing that exercise is beneficial, and that the COSA recommendations are important for patients, only a minority actually apply the recommendations in their practice. Targeted implementation efforts are needed to facilitate use of COSA exercise guidance in clinical practice.

PMID:40515951 | DOI:10.1007/s00520-025-09633-0