Nevin Manimala

Int J Transgend Health. 2025 Feb 28;27(2):1115-1129. doi: 10.1080/15532739.2025.2469279. eCollection 2026.

ABSTRACT

PURPOSE: Fertility preservation is recommended prior to initiation of gender-affirming hormone therapy. However, barriers have been described in providing appropriate counseling and pursuing fertility preservation. We hypothesized transgender and gender diverse (TGD) people serving in the United States military would face their own unique barriers to fertility preservation given the historic undulating policies with respect to their ability to openly serve. We aimed to evaluate barriers that transgender and gender diverse (TGD) individuals face when pursuing fertility preservation in the United States Military Health System (MHS).

METHODS: We developed a mixed-methods study using an explanatory sequential design. Data collection occurred between February and April 2024. We created and distributed a survey to all individuals presenting for an initial surgical consultation for gender-affirming genital reconstructive surgery at our institution and posted it on a social media page for TGD military service members. This survey assessed family-building desires, barriers to family-building, and satisfaction with prior fertility preservation counseling. In the survey, participants had the option to request a follow-up interview. We report descriptive statistics from both the survey and interviews.

RESULTS: We received 26 responses from self-identified transgender men (n = 9), transgender women (n = 14), and nonbinary (n = 3) individuals aged 21 to 49. Most respondents were married (61.5%) and desired at least one child (76.9%). The majority of respondents did not feel supported in building their families during their military service (61.5%). Twenty respondents agreed to participate in a follow-up interview, and ten interviews were conducted. Five barriers emerged from coding interviews: heterogeneity in counseling, limited resources and support, systemic barriers, providers’ implicit bias and insurance policy.

CONCLUSION: Numerous family planning and fertility preservation barriers exist for TGD people within the Military Health System. Although many individuals stated they received fertility preservation counseling, many felt it was a formality and lacked individualization. This research highlights the need to standardize fertility preservation counseling, train US military providers on fertility preservation counseling for TGD service members and pursue policy reform to decrease barriers to accessing this care.

PMID:41891058 | PMC:PMC13015071 | DOI:10.1080/15532739.2025.2469279

medRxiv [Preprint]. 2026 Mar 17:2026.03.16.26348520. doi: 10.64898/2026.03.16.26348520.

ABSTRACT

Managing postprandial glucose in Type 1 Diabetes Mellitus (T1DM) requires understanding how carbohydrate intake affects glucose through both direct pathways and insulin-mediated compensation. ^1,2 Standard analyses often treat insulin as a confounder rather than a mediator, obscuring the distinct roles of these two causal channels and hiding clinically important heterogeneity in how different patients respond to carbohydrate intake. Using meal-centered continuous glucose monitoring windows from twelve adults in the OhioT1DM 2018 and 2020 cohorts, ^3,4 we apply the causal mediation framework of Imai et al. ⁵ to decompose the total effect of carbohydrate intake on glucose change into the Average Causal Mediation Effect (ACME, the indirect effect operating through insulin), the Average Direct Effect (ADE, the effect not mediated by insulin), and the Average Total Effect (ATE). ⁶ We estimate these quantities by meal type over a 3.5-hour post-meal horizon and across outcome quantiles to characterize heterogeneity in glucose control mechanisms that population-average methods fail to detect. ^7,8 To adjust for confounding by longitudinal pre-meal physiological trajectories, we introduce a Causally-constrained Linear Autoencoder (CLAE) that learns low-dimensional pre-treatment representations satisfying the conditional independence assumptions required for valid mediation. ^9-11 Results reveal clinically meaningful heterogeneity in response to carbohydrate and bolus insulin intake across meal types and across the conditional glucose response distribution. At dinner, the direct glycemic effect substantially exceeds the insulin-mediated response, producing persistent total effects of 10-14 mg/dL for a +30 g carbohydrate increase that indicates systematic under-compensation by evening boluses. Breakfast, in contrast, exhibits large but nearly canceling direct and mediated effects, while lunch and snack show negligible mediation structures. Quantile-specific analysis further identifies a subgroup for whom the total carbohydrate effect at dinner reaches 22.03 mg/dL ( p = 0.04), statistically significant despite being undetectable in the mean-level analysis. This distributional heterogeneity points to patients whose glycemic risk is undermined by population-average estimates and for whom current dosing recommendations are inadequate. ^12-14.

PMID:41891047 | PMC:PMC13015663 | DOI:10.64898/2026.03.16.26348520

medRxiv [Preprint]. 2026 Mar 16:2026.03.13.26347917. doi: 10.64898/2026.03.13.26347917.

ABSTRACT

IMPORTANCE: Eating disorders (EDs) are heritable, yet the developmental pathways through which genetic liability manifests in early life remain unclear.

OBJECTIVE: To investigate the associations between genetic liability for anorexia nervosa (AN) and binge eating (BE) and disordered eating behaviors (DEB) across childhood, and to identify the mediating roles of metabolic and psychosocial traits.

DESIGN SETTING AND PARTICIPANTS: This longitudinal observational study used genomic and behavioral data from the Adolescent Brain Cognitive Development ^SM (ABCD ^® ) Study, a multisite, population-based cohort of children recruited between 2016 and 2018 at ages 9 to 10 years from 21 research centers across the United States. A three-wave temporal design was employed, utilizing data from baseline (T0), Year 1 (T1), and Year 2 (T2) follow-ups. Primary analyses focused on 5,618 participants of genetically inferred European (EUR) ancestry, with exploratory analyses conducted in a diverse sample of 9,132 participants.

EXPOSURES: Polygenic scores (PGS) for AN and BE were calculated using summary statistics from the most recent genome-wide association studies. Mediators included BMI, ADHD, anxiety/depression, and social problems from the Child Behavioral Checklist assessed at Year 1 follow-up (T1).

MAIN OUTCOMES AND MEASURES: Parent reported DEB symptoms via the Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS). For longitudinal association analyses, DEB were pooled across T0, T1 and T2 to assess the relationship between genetic liability and childhood symptom severity. For mediation analyses, DEB at T2 follow-up were used to ensure a clear temporal sequence between mediators at T1 and the outcomes.

RESULTS: Among 5,618 EUR participants (mean [SD] age, 9.91 [0.62] years; 47% female), longitudinal association models revealed that higher AN-PGS was associated with increased AN symptoms, while BE-PGS was associated with increased BE and AN symptoms. These patterns were largely consistent in exploratory cross-ancestry analyses. Mediation analyses showed that BMI mediated genetic risks across sexes, while ADHD and anxiety/depression symptoms emerged as additional mediators in females.

CONCLUSIONS AND RELEVANCE: Genetic liabilities to AN and BE contribute to childhood DEB through sex-dependent pathways, highlighting the developmental continuity of ED risk from childhood. Integrating genetic profiles with behavioral markers may facilitate early identification and support multifaceted interventions.

KEY POINTS QUESTION: Do genetic risks for anorexia nervosa (AN) and binge eating (BE) contribute to childhood disordered eating behaviors, and what mechanisms mediate these effects?

FINDINGS: In this longitudinal study of 5,618 children of European ancestry, AN polygenic scores (AN-PGS) were associated with early AN symptoms, while BE-PGS showed transdiagnostic associations with both AN and BE symptoms. These links were mediated by BMI and psychosocial traits, including sex-specific pathways through ADHD and anxiety/depression symptoms in females.

MEANING: Our findings suggest that genetic liability to eating disorders manifests early in life through distinct metabolic and psychosocial pathways, highlighting a window for sex-specific targeted prevention.

PMID:41891041 | PMC:PMC13015685 | DOI:10.64898/2026.03.13.26347917

medRxiv [Preprint]. 2026 Mar 16:2026.03.14.26348336. doi: 10.64898/2026.03.14.26348336.

ABSTRACT

The digital clock drawing test (dCDT) is a cognitive screening tool employing a digital pen. While many studies rely on summary statistics of dCDT features to predict cognitive outcomes, these approaches often involve subjective decisions such as feature selection and imputation. In this study, we introduce novel dCDT features, expressed as mathematical functions, and compare them to commonly used summary features. We included dCDTs from 3,415 participants from the Framingham Heart Study. Random forest models with five-fold cross-validation were trained to distinguish participants with mild cognitive impairment or dementia from cognitively intact participants. When combined with established time-based features, functional features related to spatial proximity and circularity demonstrated predictive power comparable to commonly used summary features. Our findings highlight the potential of integrating functional features to detect subtle motions and behaviors in digital cognitive assessments, offering new tools that may enhance diagnostic accuracy and support early detection strategies.

PMID:41891039 | PMC:PMC13015632 | DOI:10.64898/2026.03.14.26348336

medRxiv [Preprint]. 2026 Mar 19:2025.01.04.25319877. doi: 10.1101/2025.01.04.25319877.

ABSTRACT

Detecting viral RNA from wastewater has emerged as a cost-effective approach for community-level surveillance during the recent SARS-CoV-2 pandemic. Although various concentrating methods have been developed, none are optimal for all key requirements for wastewater viral detection. Freeze-drying, a technique widely used for concentrating and preserving biological materials, remains underexplored for this purpose. This study compared the performance of freeze-drying and centrifugal ultrafiltration in terms of recovery efficiency, detection limit, and other key parameters. Early pandemic samples in this study, with extremely low viral concentrations, offered an ideal benchmark to assess their suitability for early-warning applications. Statistical analyses showed that freeze-drying achieved significantly higher recovery efficiency (0.338% ± 0.065% vs. 0.149% ± 0.046%), superior detection ratio (81.6% vs. 36.8%), and lower detection limit (0.06 vs. 0.36 copies/mL) compared to centrifugal ultrafiltration. To our knowledge, this is the first study to apply freeze-drying for wastewater-based viral detection. Despite its longer processing time, freeze-drying offers multiple advantages, including the elimination of pretreatment steps, a flexible workflow, reduced RNA degradation under cryogenic conditions, minimal pathogen exposure, lower labor demands, and less human interference during processing. These features position freeze-drying as a novel alternative for wastewater-based viral surveillance, particularly for decision-making when establishing such systems.

SYNOPSIS: Freeze-drying is a new wastewater virus concentrating method that outperforms centrifugal ultrafiltration, providing a simpler, safer, and more sensitive approach for community surveillance.

PMID:41891023 | PMC:PMC13015668 | DOI:10.1101/2025.01.04.25319877

medRxiv [Preprint]. 2026 Mar 17:2026.03.13.26348337. doi: 10.64898/2026.03.13.26348337.

ABSTRACT

INTRODUCTION: Particulate Matter (PM _2.5 ) exposure contributes to the global disease burden, yet its monitoring remains sparse and uneven and is limited in many limited ground monitoring network settings. Road-traffic proxy indicators can provide indirect estimates of PM _2.5 where measurements are limited but require context-specific validation. We evaluated three PM _2.5 road-traffic related proxies:(I) population-Weighted Road Network Density (WRND), (ii) Euclidean (straight line) distance from highways (EH), and (iii) Euclidean distance from main roads (EM).

METHODS: We validated proxies using high-resolution outdoor filtered PM _2.5 personal exposure measurements collected over 1 year from 343 postpartum participants in The Gambia, Kenya, and Mozambique. Village-level spatial patterns for the PM _2.5 -proxy relationship were mapped using 5 km hexagonal aggregated tessellations. Proxy-PM _2.5 associations were assessed using Spearman correlation, and predictive utility was tested using country-specific and global Random Forest (RF) models (3-fold cross-validation), reporting R ² , RMSE, and feature importance.

RESULTS: Spatial mapping showed heterogeneous proxy-PM _2.5 relationships across and within sites, with elevated PM _2.5 occurring in both low- and high-proxy contests. WRND-PM _2.5 correlations were weak overall and statistically significant only in Mozambique (r = 0.351; p = 0.005 ), with non-significant associations in Kenya (r = -0.041; p = 0.673 ) and The Gambia (r = -0.020; p = 0.909 ). EH-PM _2.5 correlations were positive in The Gambia (r = 0.335; p = 0.053 ) and Mozambique (r = 0.292; p = 0.020 ) but negative and significant in Kenya (r = -0.224; p = 0.018 ).Single-variable RF models performed poorly across all countries (R ² < 0.45) and the Global model (R ² =0.42). Combining proxies improved performance in Kenya (R ² =0.52; RMSE=31.7µg/m ³ ) and Mozambique (R ² =0.60; RMSE=8.9 µg/m ³ ), Global R ² =0.46; RMSE=29.1 µg/m ³ ), although in The Gambia, the combined model (R ² =0.53; RMSE=37.6 µg/m ³ ) did not exceed the best single-proxy model.

CONCLUSION: Road-network proxies provide context-dependent signals of personal PM _2.5 exposure, and predictive performance is strengthened when proxies are combined in a hybrid model.

PMID:41891017 | PMC:PMC13015645 | DOI:10.64898/2026.03.13.26348337

medRxiv [Preprint]. 2026 Mar 20:2026.03.18.26348637. doi: 10.64898/2026.03.18.26348637.

ABSTRACT

BACKGROUND: The clinical safety profile of e-cigarette use for smoking reduction remains poorly characterized. This study compared the relative safety and tolerability of nicotine e-cigarette use with non-nicotine e-cigarettes or a non-aerosol cigarette substitute (CS) among adults interested in reducing their smoking.

METHODS: We conducted a secondary analysis of adverse events (AEs) reported in a 6-month, double-blind RCT involving 520 participants assigned to either e-cigarettes with 0, 8, or 36 mg/mL nicotine or a CS. AEs were coded using CTCAE V4.0 and assessed for frequency, severity, seriousness and relatedness across groups. Cumulative incidence was calculated over 24 weeks. We estimated risk differences (RDs) and 95% confidence intervals (CIs) for frequently reported AEs (≥1% of participants overall) comparing e-cigarette vs. CS and nicotine versus non-nicotine e-cigarette groups. Fisher’s exact test, with adjustment for multiple comparisons, was used to assess statistical significance.

RESULTS: Most study-related AEs (those rated as possibly, probably, or definitely related by medical monitor) were mild in severity and none were classified as serious. At 24 weeks, cumulative incidence of first study-related AE was highest in the 36 mg/mL (37.0%) and 8 mg/mL (35.2%) e-cigarette groups, followed by 0 mg/mL (23.4%), and lowest in CS group (2.5%). E-cigarette users experienced significantly greater risks of cough (RD [95%CI]: 8.5% [5.6 – 11.3]), headache (RD [95%CI]: 5.4% [3.3 – 7.6]) and sore throat (RD [95%CI]: 5.4% [3.2 – 7.6]) as compared with the CS group. Cough was also more common in those randomized to nicotine versus non-nicotine e-cigarettes (RD [95%CI]: 8.1% [3.4 – 12.8]).

CONCLUSION: All study products were generally well-tolerated; however, AEs were more common in e-cigarette groups, especially with nicotine. Findings highlight the need to monitor common symptoms such as cough, headache, and sore throat in clinical and regulatory evaluations of e-cigarette safety.

WHAT IS ALREADY KNOWN ON THIS TOPIC: Nicotine e-cigarettes can help people who smoke to quit combustible cigarette use and reduce some cigarette-related toxicant exposures. However, the safety of inhaled nicotine and other constituents such as propylene glycol, vegetable glycerin in e-cigarettes remains unclear.

WHAT THIS STUDY ADDS: This study suggests that e-cigarette use is associated with a higher incidence of study-related AEs such as cough, headache, and sore throat, particularly among those using nicotine-containing products. However, overall safety and tolerability profiles were comparable across e-cigarette groups with differing nicotine concentrations.

HOW THIS STUDY MIGHT AFFECT RESEARCH PRACTICE OR POLICY: These findings offer methodological guidance for evaluating e-cigarette safety in clinical trials and may inform regulators, clinicians, and public health professionals regarding the tolerability of e-cigarette products varying in nicotine concentration.

PMID:41891015 | PMC:PMC13015618 | DOI:10.64898/2026.03.18.26348637

Ann Clin Transl Neurol. 2026 Mar 26. doi: 10.1002/acn3.70373. Online ahead of print.

ABSTRACT

OBJECTIVE: Stereoelectroencephalography-guided radiofrequency thermocoagulation (SEEG-RFTC) has emerged as a safe and effective minimally invasive treatment for children with drug-resistant focal epilepsy. Although evidence from real-world studies remains limited, numerous pediatric cases have demonstrated promising outcomes. This retrospective study aimed to evaluate the seizure outcomes of SEEG-RFTC in pediatric patients and identify predictive factors associated with seizure freedom.

METHODS: A retrospective observational study was conducted across two epilepsy centers, including 111 children with drug-resistant epilepsy who underwent SEEG-RFTC. Postoperative outcomes were assessed primarily by the rate of seizure freedom at the last follow-up (minimum 1 year). Potential predictive factors were analyzed through comparisons of clinical, neuroimaging, electrophysiological, and etiological variables.

RESULTS: All patients were followed for at least 1 year post-procedure, with 73 (65.8%) achieving seizure freedom. Among 46 patients with focal cortical dysplasia, the seizure-free rate was 80.4%. In 10 patients with hippocampus sclerosis, 6 (60%) were seizure-free at the final follow-up. Statistical analysis identified the course of illness (p < 0.01) and positron emission tomography (PET) findings (p = 0.01) as significant predictors of seizure freedom.

CONCLUSION: SEEG-RFTC is a safe procedure that yields favorable outcomes in a substantial proportion of pediatric patients with drug-resistant focal epilepsy. The duration of epilepsy and PET characteristics are significantly associated with the likelihood of achieving seizure freedom. These findings highlight the potential of SEEG-RFTC as a valuable therapeutic option in this population.

PMID:41888055 | DOI:10.1002/acn3.70373

Rural Remote Health. 2026 Mar;26(1):9712. doi: 10.22605/RRH9712. Epub 2026 Mar 26.

ABSTRACT

INTRODUCTION: Pathways aimed at increasing the medical workforce in regional and rural areas in Aotearoa New Zealand have been implemented in universities, such as the Regional and Rural Admission Scheme (RRAS) at Waipapa Taumata Rau | The University of Auckland, to address urban-rural variations in health outcomes. A recent review of the university’s scheme suggested the program was not providing equitable opportunities for students from a rural background as originally intended. Therefore, an updated RRAS was required to be developed to address these inequities, creating a more genuine scheme that may more strongly contribute to developing the regional and rural workforce in New Zealand.

METHODS: We developed a methodological framework to identify and evaluate candidate rural definitions for the purposes of developing a new RRAS for the university. Following an extensive literature review, we utilised two sets of criteria to select candidate rural definitions, which were then evaluated using visual evaluation (mapping) and exploratory analysis. Candidate definitions were modified to use a three-group (rural-regional-urban) version to be suitable for use as an updated RRAS. We used a de-identified student dataset of applicants enrolled for the MBChB medical program at the University of Auckland from 2017 to 2023 (inclusive) and population counts from the New Zealand 2018 Census to investigate differences in potential admission numbers under each candidate definition. The New Zealand Index of Multiple Deprivation 2018 was used to assess the distribution of potential admission numbers by area-level socioeconomic status. We also examined the suitability of the candidate definitions by ethnicity, specifically for students of M&#257;ori ethnicity.

RESULTS: We selected two candidate definitions for exploratory analysis: Geographic Classification for Health (GCH) developed by the University of Otago, and the urban accessibility classification 2020 (UA 2020) by Stats NZ. We found that the three-group modified version of the UA 2020 definition consistently classified a higher proportion of students as regional and rural compared to the current RRAS and the alternative candidate definition, the three-group GCH. The modified UA 2020 was found to classify a higher number of M&#257;ori students and those living in less-deprived neighbourhoods as rural when compared to the other definitions. Therefore, our final recommendation is to update the existing RRAS using a three-group modified version of the UA 2020 by Stats NZ. Our proposed version will refocus attention to address the under-representation of rural students admitted to professional health programs at the University of Auckland, while not disadvantaging regional students.

CONCLUSION: The updated RRAS will assist in supplementing the future professional rural medical workforce, and subsequently help to reduce health outcome variations between rural and urban areas in New Zealand. The modified UA 2020 is likely to be updated regularly by Stats NZ, and therefore the RRAS can be kept up to date in the future.

PMID:41888043 | DOI:10.22605/RRH9712

Int J Audiol. 2026 Mar 26:1-10. doi: 10.1080/14992027.2026.2642750. Online ahead of print.

ABSTRACT

OBJECTIVE: Digital hearing aid processing introduces delay. While traditional literature suggests a 10-ms threshold, evidence indicates that even shorter delays may degrade sound quality. This study examined the impact of Ultra-Low Delay (ULD; 0.5 ms) versus Standard Delay (SD; 2.7 ms) on temporal and spectral auditory processing abilities in hearing aid users.

DESIGN AND STUDY SAMPLE: Twenty experienced hearing aid users (aged 41-75 years) with bilateral, symmetrical, mild-to-moderate sensorineural hearing loss participated. Auditory performance was assessed under the ULD and SD conditions using the Frequency Pattern Test, Duration Pattern Test, Random Gap Detection Test, and Spectral-Temporally Modulated Ripple Test.

RESULTS: Statistical analyses revealed significant differences between the two processing delay conditions across all evaluated tests (p < .01). Participants demonstrated statistically superior temporal and spectral processing performance under the ULD condition compared to the SD condition.

CONCLUSIONS: The findings demonstrate that the ULD condition significantly improves central auditory temporal and spectral processing abilities compared to the SD condition. These results challenge the traditional view that delays under 10 ms are negligible and highlight the clinical importance of ultra-low delay technology for preserving auditory resolution in individuals with hearing loss.

PMID:41888031 | DOI:10.1080/14992027.2026.2642750