Categories
Nevin Manimala Statistics

Actionable biomarker co-expression in advanced ovarian cancer: folate receptor alpha expression and related markers

Int J Gynecol Cancer. 2026 Aug 6:104893. doi: 10.1016/j.ijgc.2026.104893. Online ahead of print.

ABSTRACT

BACKGROUND: Folate receptor-α is an established therapeutic target in ovarian cancer and identifies candidates for mirvetuximab soravtansine. However, co-expression patterns between folate receptor-α and other actionable biomarkers, and their therapeutic implications, remain incompletely characterized.

METHODS: We conducted a single-institution cohort study of 110 patients with platinum-resistant ovarian cancer treated with mirvetuximab soravtansine (2019-2025). Tumor biomarkers were assessed using immunohistochemistry, fluorescence in situ hybridization, and next-generation sequencing. Co-expression among 10 biomarkers, including folate receptor-alpha, estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2, BRCA, homologous recombination/loss of heterozygosity, programmed death-ligand 1, claudin-6, and tumor mutational burden, were evaluated using Jaccard similarity indices, Cohen’s kappa statistics, and correlation analyses. Exploratory progression-free survival and overall survival analyses were performed by folate receptor-α and estrogen receptor sub-groups.

RESULTS: Folate receptor-α expression was high in 80% of tumors and intermediate/low in 20%. Co-expression analyses demonstrated largely independent biomarker patterns, reflecting biological heterogeneity. A hormone receptor-associated cluster emerged, including strong co-expression between folate receptor-α and estrogen receptor (Jaccard = 0.76), and moderate overlap between estrogen receptor and claudin-6 (0.62), programmed death-ligand-1 and estrogen receptor (0.56), and programmed death-ligand-1 and folate receptor-α (0.50). Survival outcomes were comparable between folate receptor-α-high and folate receptor-α-intermediate/low tumors. Among folate receptor-α-high tumors, estrogen receptor expression (≥10%) did not meaningfully stratify progression-free or overall survival outcomes.

CONCLUSIONS: Biomarker co-expression in advanced ovarian cancer demonstrates substantial heterogeneity, with patterns that may inform future biomarker-guided treatment combinations and sequencing strategies. Prospective validation is needed to refine multi-marker frameworks and determine whether biologically driven treatment approaches based on co-expression biomarker patterns may have clinical utility. Exploratory analyses support further investigation of folate receptor-α as a potentially graded rather than strictly binary biomarker; however, these findings are hypothesis-generating.

PMID:42642279 | DOI:10.1016/j.ijgc.2026.104893

Categories
Nevin Manimala Statistics

Toward unified and comprehensive automated electroencephalogram interpretation: a multicentre development and validation of an electroencephalogram foundation model

Lancet Digit Health. 2026 Aug 25:101039. doi: 10.1016/j.landig.2026.101039. Online ahead of print.

ABSTRACT

BACKGROUND: Electroencephalogram (EEG) interpretation is essential for neurological diagnosis, but expert interpretation is limited globally, and existing AI methods address narrow tasks. This study aimed to develop and externally validate a broadly applicable foundation model capable of expert-level performance across diverse EEG tasks and clinical settings.

METHODS: In this multicentre study we developed a multidomain omnibus for reading and generalising over thorough EEG interpretation (MORGOTH), a foundation model that supports broad clinical interpretation across all major settings. We developed MORGOTH using EEGs from 18 677 patients across Massachusetts General Hospital, Brigham and Women’s Hospital, Beth Israel Deaconess Medical Center, and Boston Children’s Hospital, collected between Jan 1, 2003, and Feb 1, 2025, and validated it internally on 13 334 patients and externally on 1573 patients from 48 institutions, spanning diverse clinical settings and ages (0 years to >90 years). Test datasets annotated by six to 30 experts enabled inter-rater reliability (IRR) analysis by comparing model-expert and expert-expert agreement. MORGOTH was compared against both human experts and state-of-the-art models using area under the curve (AUC) and the percentage of experts’ operating points under the curve (EUC) for receiver operating characteristic (ROC) and precision-recall curves, as well as IRR and statistical calibration.

FINDINGS: MORGOTH achieved expert-level performance with AUC-ROC scores of 0·86 to 0·98 across 17 EEG findings. MORGOTH outperformed at least 90% of experts on three of seven multi-expert-annotated datasets and exceeded at least 20% of experts on each of the 17 tasks. Event-level performance was especially strong for seizure and ictal-interictal-injury continuum detection (EUC=96·6%) and spike detection (EUC=100%). IRR analysis showed that MORGOTH matched or exceeded expert consensus. External validation confirmed consistent performance with modest declines from internal to external test sets (event-level AUC -1·21%, EUC -3·33%; EEG-level AUC -2·12%, and EUC -9·52%). MORGOTH performance also remained robust across age, sex, and moderate channel loss, with lower age sensitivity (20·90% vs 30·90%) and fewer sex-related differences (33·33% vs 44·00%) than SPaRCNet.

INTERPRETATION: MORGOTH advances automated EEG interpretation with expert-level performance across clinical settings, offering improved diagnostic accuracy in low-resource environments and greater efficiency in high-volume centres.

FUNDING: US National Institutes of Health.

PMID:42642264 | DOI:10.1016/j.landig.2026.101039

Categories
Nevin Manimala Statistics

Persistent Vocal Alterations and Throat Clearing in Professional Singers Following COVID-19 Infection: A Cross-Sectional Study from China

J Voice. 2026 Aug 26:S0892-1997(26)00420-0. doi: 10.1016/j.jvoice.2026.08.004. Online ahead of print.

ABSTRACT

Professional singers represent a uniquely vulnerable population whose livelihoods depend on optimal vocal function, yet the specific impact of COVID-19 infection on their voice health remains insufficiently characterized. We conducted a cross-sectional observational study through an anonymous online survey distributed via Wenjuanxing among professional singers in mainland China between January and June 2025. A total of 154 participants (mean age 35.8 years, 59.2% female) with at least 2 years of professional singing experience and confirmed COVID-19 infection completed a structured questionnaire that collected demographic information, infection details, self-reported vocal symptoms, and standardized voice handicap assessments using the Mandarin Chinese version of the Voice Handicap Index-10 (VHI-10). Statistical associations were analyzed using prevalence ratios with 95% confidence intervals calculated via generalized linear models. Vocal alterations were reported by 62% of singers during the acute phase and by 53% after recovery, while new-onset throat clearing emerged in 44% of participants exclusively in the postinfection period. Self-perceived voice impairment was present in 65.6% of participants, with a mean VHI-10 score of 14.8 (SD = 7.2). COVID-19 infection was significantly associated with vocal impairment (prevalence ratio = 2.33, 95% CI: 1.04-5.46, P = 0.03) and throat clearing (prevalence ratio = 9.13, 95% CI: 2.47-64.42, P = 0.001). After adjustment for age, gender, and years of professional experience, these associations remained clinically meaningful at 2.29 and 8.97, respectively. Correlation analysis revealed strong positive relationships between symptom severity and VHI-10 scores (r = 0.68 for voice impairment, r = 0.74 for throat clearing). Our findings demonstrate that COVID-19 infection more than doubles the risk of voice impairment and increases the likelihood of new-onset throat clearing nearly ninefold among professional singers. This study provides novel evidence from a Chinese cohort, highlighting the critical need for targeted voice care protocols and routine postinfection voice assessment in this high-demand occupational group.

PMID:42642245 | DOI:10.1016/j.jvoice.2026.08.004

Categories
Nevin Manimala Statistics

Online, Crowdsourced Sampling (OCS) Platforms for Large-Scale Data Collection in Voice Disorders Research: Prices, Pitfalls, and Perks

J Voice. 2026 Aug 25:S0892-1997(26)00402-9. doi: 10.1016/j.jvoice.2026.07.049. Online ahead of print.

ABSTRACT

OBJECTIVE: Online, crowdsourced sampling (OCS) platforms such as Amazon’s Mechanical Turk and CloudResearch Connect enable faster, cheaper, and larger-scale data collection than in-person sampling methods. However, OCS platforms are often criticized due to data quality concerns. This study examines a battery of screening tools to determine which best predicts data quality and to quantify the influence of low-quality data on the statistical properties of the samples. Finally, we issue recommendations to researchers interested in OCS-based clinical voice research that may reduce costly missteps when fielding their first OCS studies.

METHODS: To evaluate the suitability of OCS for clinical voice research, survey-based measures of vocal function, vocal fatigue, personality, communicative quality of life, and other factors were collected on Qualtrics from (1) a convenience sample of undergraduate students (n = 47), (2) Mechanical Turk users (n = 495), and (3) Connect users (n = 99) over 6 months. Low-quality responses were eliminated using six screening tools in four nested stages. Logistic regression was used to identify variables that strongly predicted data quality. Finally, patient-reported outcome measure (PROM) responses were compared between the high- and low-quality groups.

RESULTS: Depending on the stage, data quality screenings flagged between 5.00% (n = 32) and 13.6% (n = 87) of responses as low-quality. Hispanic/Latino ethnicity and long response times most strongly predicted low-quality responses, which uniformly exhibited more severe ratings of health- and voice-related disability than did high-quality responses.

CONCLUSIONS: Content-based screenings, particularly analysis of responses to open-ended questions, meaningfully augmented automated screenings. Low-quality respondents systematically over-reported health- and voice-related disability, a severity bias with plausible economic and behavioral explanations. The emergence of AI-generated responses represents an evolving and distinct challenge that content-based screening may be increasingly insufficient to address. We provide recommendations for collecting high-quality data on OCS platforms to minimize barriers to entry for future clinical voice research.

PMID:42642244 | DOI:10.1016/j.jvoice.2026.07.049

Categories
Nevin Manimala Statistics

Progression of Cervical Ossification of the Posterior Longitudinal Ligament: A Systematic Review and Meta-Analysis of Risk Factors, Surgical Approaches, and Reoperation Rates

Int J Spine Surg. 2026 Aug 25:8939. doi: 10.14444/8939. Online ahead of print.

ABSTRACT

BACKGROUND: Cervical ossification of the posterior longitudinal ligament (OPLL) frequently progresses despite decompression surgery, leading to recurrent myelopathy. This meta-analysis aims to quantify risk factors for OPLL progression, compare surgical strategies, and determine the pooled reoperation rate due to symptomatic progression.

METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, 26 high-quality studies comprising 1929 patients were included. Standardized mean differences (SMDs) and odds ratios (ORs) with 95% confidence intervals were calculated to assess risk factors, and all of the analyses were done with a random-effects model. A network meta-analysis using a random-effects model was conducted to compare surgical approaches, utilizing laminoplasty (LP) as the reference node.

RESULTS: Significant demographic risk factors for OPLL progression included younger age (SMD: -0.68, P < 0.001) and higher body mass index (SMD: 0.43, P < 0.001). Radiographically, progression was strongly driven by longer preoperative OPLL (SMD: 0.42, P = 0.003), a lower preoperative cervical range of motion (SMD: -0.30, P = 0.039), and OPLL at the C3 level (OR: 7.04, P < 0.001). Mixed-type OPLL nearly tripled the progression risk (OR: 2.94, P < 0.001), whereas segmental-type was highly protective (OR: 0.13, P < 0.001).The network meta-analysis demonstrated that motion-preserving posterior surgeries were associated with higher rates of OPLL progression. Compared with LP, anterior surgery provided the greatest reduction in progression risk (OR 0.28, P < 0.001), followed by laminectomy with fusion (OR 0.42, P < 0.001). Direct pairwise comparisons similarly confirmed that laminectomy with fusion significantly reduced the likelihood of progression compared with LP (OR 0.44, P = 0.002). Nonsurgical management was also associated with lower odds of progression; however, this finding should be interpreted with caution due to potential confounding by indication. Additionally, the pooled long-term reoperation rate due to neurological deterioration from OPLL progression was 6.1% (95% confidence interval 2.9%-10.2%) over a mean follow-up of 72.6 ± 63.7 months.

CONCLUSIONS: OPLL progression is statistically predictable, driven by younger age, higher body mass index, reduced cervical range of motion, and mixed-type morphology. Because anterior and fusion procedures were associated with lower progression rates compared with LP, these approaches should be considered in high-risk patients; however, these findings should be interpreted with caution given the heterogeneity across included studies.

CLINICAL RELEVANCE: For patients with high-risk profiles (eg, mixed-type OPLL), fusion or anterior decompression should be strongly considered over LP. When laminoplasty is used in high-risk patients, they should be advised on the necessity of long-term surveillance.

PMID:42642207 | DOI:10.14444/8939

Categories
Nevin Manimala Statistics

M-Wave and F-Wave Parameters in Relation to Recording Electrode Placement

Ann Rehabil Med. 2026 Aug 26. doi: 10.5535/arm.260035. Online ahead of print.

ABSTRACT

OBJECTIVE: To clarify the influence of recording electrode placement on F-wave parameters, we investigated F-wave parameters recorded from the abductor pollicis brevis muscle using different recording electrode positions.

METHODS: Thirteen healthy volunteers participated. Recording electrodes were placed at four locations (20, 30, 40, and 50 mm from the reference electrode). The stimulating electrode was positioned over the median nerve at the wrist, and the reference electrode was placed on the distal tendon of the abductor pollicis brevis muscle. Stimulation intensity was set at 1.2 times that required to elicit the maximal M-wave amplitude. Thirty stimuli were delivered at 0.5 Hz. Outcome measures included M-wave latency and amplitude, F-wave mean latency and amplitude, F/M amplitude ratio, and F-wave persistence. Data were analyzed using one-way repeated-measures analysis of variance, and effect sizes were calculated using partial η².

RESULTS: M-wave amplitude varied substantially according to recording electrode position (partial η²=0.50). In contrast, effect sizes were small for most F-wave parameters. The F/M amplitude ratio did not reach statistical significance but demonstrated a moderate-to-large effect size (partial η²=0.24).

CONCLUSION: Recording electrode placement substantially affected M-wave amplitude and may also influence the F/M amplitude ratio. Therefore, consistent electrode placement should be maintained when interpreting these parameters in clinical or research settings. However, given the relatively small sample size, clinically meaningful effects on other F-wave parameters cannot be excluded and should be investigated in larger studies.

PMID:42642177 | DOI:10.5535/arm.260035

Categories
Nevin Manimala Statistics

Anti-Müllerian hormone is a poor predictor of pregnancy with and without assisted reproductive technology: A population-based register study of 43,269 Danish women

Taiwan J Obstet Gynecol. 2026 Sep;65(5):944-951. doi: 10.1016/j.tjog.2026.07.002.

ABSTRACT

OBJECTIVE: Anti-Müllerian hormone (AMH) is widely used as a marker of ovarian reserve, but its predictive value for pregnancy remains uncertain. We aimed to evaluate whether pre-pregnancy AMH predicts pregnancy with or without assisted reproductive technology (ART).

MATERIALS AND METHODS: This population-based register study included women aged 18-50 years from the Copenhagen Capital Region with a baseline AMH measurement between 2010 and 2022. Data were linked to national health registers via Statistics Denmark. The primary outcome was confirmed pregnancy, defined by the presence of a first-trimester biochemical screening (PAPP-A and free β-hCG). Women were stratified into subgroups based on ART (yes/no) and maternal age (<25, 25-30, 30-35, 35-40, >40 years). Associations were assessed using multivariable regression and ROC curve analysis.

RESULTS: Of 43,269 women, 27,395 women had a confirmed pregnancy, and 15,874 women did not within a 3-year follow-up period after measurement of AMH. We found an overall positive association between AMH and confirmed pregnancy, adjusted for age, fertility treatment and relevant comorbidities. ROC analyses showed modest predictive value (AUC 0.50-0.69), highest in women >40 years without ART.

CONCLUSION: AMH was positively associated with pregnancy but with a poor predictive value.

PMID:42642154 | DOI:10.1016/j.tjog.2026.07.002

Categories
Nevin Manimala Statistics

Long-term psychosocial outcomes after HIFU for uterine fibroids: Interplay between symptom severity and psychological distress

Taiwan J Obstet Gynecol. 2026 Sep;65(5):932-937. doi: 10.1016/j.tjog.2026.04.001.

ABSTRACT

OBJECTIVE: To evaluate the long-term effects of HIFU ablation on quality of life, symptom severity, and psychological states (depression, anxiety, and stress) in women with uterine fibroids at least two years post-treatment.

MATERIALS AND METHODS: This retrospective cohort study investigated 38 patients who underwent HIFU ablation for uterine fibroids at Chung Shan Medical University Hospital from 2015 to December 2018. Participants completed validated questionnaires including the Depression, Anxiety, and Stress Scale-21 Items (DASS-21) and the Uterine Fibroid Symptom and Health-related Quality of Life (UFS-QOL) questionnaire. Statistical analyses included descriptive statistics, correlation analysis, ANOVA, and logistic regression.

RESULTS: The mean patient-rated symptom severity score (SSS) was 28.87, and the mean total health-related quality of life (HRQOL) score was 61.39. Over 60% of patients demonstrated normal scores in depression, anxiety, and stress domains. Significant negative correlations were found between HRQOL items and symptom severity scale (all p < 0.05). Positive correlations were observed between symptom severity and depression/anxiety/stress scores. For each one-point increase in disease severity, the likelihood of experiencing depression, anxiety, and stress increased by 1.041, 1.043, and 1.027 times, respectively.

CONCLUSION: HIFU ablation demonstrates favorable and sustained long-term efficacy in managing symptoms. Crucially, psychological well-being plays a central role in determining long-term quality of life, with psychological factors explaining a significant proportion of HRQOL variance. This interplay underscores the necessity of integrating routine psychological screening (such as DASS-21) and adopting a holistic, multidisciplinary approach to long-term follow-up care for uterine fibroid patients.

PMID:42642152 | DOI:10.1016/j.tjog.2026.04.001

Categories
Nevin Manimala Statistics

Scaling pleasure-based sexual and reproductive health: an impact and economic modelling study in 99 low- and middle-income countries

BMJ Glob Health. 2026 Aug 25;11(8):e024479. doi: 10.1136/bmjgh-2026-024479.

ABSTRACT

INTRODUCTION: Pleasure is a key reason why people have sex. Yet many sexual and reproductive health (SRH) programmes do not consider the fundamental role of pleasure, focusing primarily on the prevention of pregnancy and sexually transmitted infections. Moreover, there is limited policy-ready evidence on pleasure-based sexual and reproductive healthcare (PBSRH), including implementation guidance, costs, impacts and return on investment at scale.

METHODS: We conducted semi-structured interviews with nine PBSRH providers to characterise the incremental activities required to implement PBSRH relative to conventional SRH. Using activity-based costing, we estimated the costs of integrating pleasure principles into existing SRH programmes for 15-24-year-olds in 99 low- and middle-income countries (LMICs) over 2026-2035. We focused on a narrow behavioural pathway – increased condom use – and projected its effects on (1) Unintended pregnancies, abortions, maternal and child mortality using methods consistent with Guttmacher’s Adding it Up approach and (2) HIV outcomes using the Goals-Spectrum application. We undertook a prospective, societal benefit-cost analysis to estimate global, regional and country-level return on investment.

RESULTS: Eighteen incremental activities are commonly undertaken when integrating pleasure into SRH programmes. The estimated incremental cost of these activities for 15-24 year olds in LMICs is $1.6 billion (95% CI $1.1 to $2.2) over 10 years. This is expected to lead to 30.7 million (95% CI 17.8 to 41.1) additional years of condom use, averting 4.3 million pregnancies (95% CI 2.1 to 6.7) and 2.1 million abortions (95% CI 1.1 to 3.4). PBSRH integration would avert 92 318 deaths by 2050 (95% CI 47 965 to 139 835), ~80% relating to women and children. The expected return on investment is $22.9 (95% CI $13.8 to $37.6) in benefits per $1 of incremental cost. The largest benefits and returns are in Sub-Saharan Africa and Latin America and the Caribbean.

CONCLUSION: PBSRH is a cost-effective and high-return intervention to support global SRHR and HIV/AIDS goals for young people in LMICs.

PMID:42642104 | DOI:10.1136/bmjgh-2026-024479

Categories
Nevin Manimala Statistics

Chronic traumatic encephalopathy in former NFL players

BMJ. 2026 Aug 25;394:e100526. doi: 10.1136/bmj-2026-100526.

NO ABSTRACT

PMID:42642089 | DOI:10.1136/bmj-2026-100526