Nevin Manimala

JAMA Dermatol. 2025 Feb 12. doi: 10.1001/jamadermatol.2024.6434. Online ahead of print.

ABSTRACT

IMPORTANCE: Frontal fibrosing alopecia (FFA) is an inflammatory and scarring form of hair loss of increasing prevalence that most commonly affects women. An improved understanding of the genetic basis of FFA will support the identification of pathogenic mechanisms and therapeutic targets.

OBJECTIVE: To identify novel genomic loci at which common genetic variation affects FFA susceptibility and assess nonadditive effects on genetic risk between susceptibility loci.

DESIGN, SETTING, AND PARTICIPANTS: Four genome-wide association studies were combined using an SE-weighted meta-analysis. Within the major histocompatibility complex (MHC) locus, stepwise conditional analysis was undertaken to determine independently associated classical MHC class I alleles. Statistical tests for epistatic interaction were performed between risk alleles at the MHC and endoplasmic reticulum aminopeptidase 1 (ERAP1) loci.

MAIN OUTCOMES AND MEASURES: Genome-wide significant locus associated with FFA and nonadditive effects on genetic risk between susceptibility loci.

RESULTS: Of 6668 included patients, there were 1585 European female individuals with FFA and 5083 controls. Genome-wide significant associations were identified at 4 genomic loci, including a novel susceptibility locus at 5q15, and the association signal could be fine-mapped to a single nucleotide substitution (rs10045403) in the 5′ untranslated region of ERAP1 (rs10045403; odds ratio, 1.30; 95% CI, 1.19-1.43; P = 3.6 × 10-8). Within the MHC, FFA risk was statistically independently associated with HLA-A*11:01, HLA-A*33:01, HLA-B*07:02, and HLA-B*35:01. FFA risk was affected by genetic variation at the ERAP1 locus only in individuals who carried at least 1 of the MHC class I risk alleles.

CONCLUSIONS AND RELEVANCE: In this genome-wide meta-analysis, a supra-additive effect of genetic variation was found that affected peptide trimming and antigen presentation on FFA susceptibility. Patients with FFA may benefit from emerging therapeutic approaches that modulate ERAP-mediated processes.

PMID:39937552 | DOI:10.1001/jamadermatol.2024.6434

JAMA Psychiatry. 2025 Feb 12. doi: 10.1001/jamapsychiatry.2024.4534. Online ahead of print.

ABSTRACT

IMPORTANCE: Identifying anatomy causally involved in psychosis could inform therapeutic neuromodulation targets for schizophrenia.

OBJECTIVE: To assess whether lesions that cause secondary psychosis have functional connections to a common brain circuit.

DESIGN, SETTING, AND PARTICIPANTS: This case-control study mapped functional connections of published cases of lesions causing secondary psychosis compared with control lesions unassociated with psychosis. Published cases of lesion-induced psychosis were analyzed in a computational laboratory. Participants had documented brain lesions associated with new-onset psychotic symptoms without a history of psychosis. Control cases included 1156 patients with lesions not associated with psychosis. Generalizability across lesional datasets was assessed using an independent cohort of 181 patients with brain lesions who subsequently underwent neurobehavioral testing. Data were analyzed from June 2022 to April 2024.

EXPOSURES: Lesions causing secondary psychosis.

MAIN OUTCOMES AND MEASURES: Psychosis or no psychosis.

RESULTS: A total of 153 lesions from published cases were determined to be causal of psychosis, 42 of which were described as schizophrenia or schizophrenia-like (71 [46%] patients were male, 82 [54%] female; mean [SD] age, 50.0 [20.8] years). Lesions that caused secondary psychosis mapped to a common brain circuit defined by functional connectivity to the posterior subiculum of the hippocampus (84% functional overlap, family-wise error [FWE] rate corrected P < 5 × 10-5). At a lower statistical threshold (>75% overlap, FWE-corrected P < 5 × 10-4), this circuit included the ventral tegmental area, retrosplenial cortex, lobule IX and dentate nucleus of the cerebellum, and the mediodorsal and midline nuclei of the thalamus. This circuit was consistent when derived from schizophrenia-like cases (spatial r = 0.98). We repeated these analyses after excluding lesions intersecting the hippocampus (n = 47) and found a consistent functional connectivity profile (spatial r = 0.98) with the posterior subiculum remaining the center of connectivity (>75% overlap, FWE-corrected P < 5 × 10-5), demonstrating a circuit-level effect. In an independent observational cohort of patients with penetrating head trauma (n = 181), lesions associated with symptoms of psychosis exhibited significantly similar connectivity profiles to the lesion-derived psychosis circuit (suspiciousness, P = .03; unusual thought content, P = .046). Voxels in the rostromedial prefrontal cortex are highly correlated with this psychosis circuit (spatial r = 0.82), suggesting the rostromedial prefrontal cortex as a promising transcranial magnetic stimulation target for psychosis.

CONCLUSIONS AND RELEVANCE: Lesions that cause secondary psychosis affect a common brain circuit in the hippocampus. These results can help inform therapeutic neuromodulation targeting.

PMID:39937525 | DOI:10.1001/jamapsychiatry.2024.4534

JAMA Netw Open. 2025 Feb 3;8(2):e2457666. doi: 10.1001/jamanetworkopen.2024.57666.

ABSTRACT

IMPORTANCE: Dust storms are projected to increase with climate change. The short-term health outcomes associated with dust storms in the US are not well characterized, especially for morbidity outcomes.

OBJECTIVE: To estimate associations between dust storms and diagnosis-specific emergency department (ED) visits during 2005 to 2018.

DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study using a time-stratified case-crossover design, short-term associations between dust storms and ED visits were estimated at the zip code level using conditional Poisson analysis with adjustment for meteorology and within-month trends. Same-day dust storm events and storm events within a lag period of up to 7 days were considered. State-wide patient-level ED visit records acquired from 3 state health departments (Arizona, California, and Utah) were analyzed. Data were analyzed between April 21 and November 12, 2024.

EXPOSURES: Dust storm events were reported by the US National Weather Service and assigned to each patient zip code that had at least a 5% areal overlap with the National Weather Service forecast zone.

MAIN OUTCOMES AND MEASURES: Patient-level ED visits for asthma, chronic obstructive pulmonary disease, culture-negative pneumonia, congestive heart failure (CHF), cerebrovascular disease, ischemic heart disease, and visits due to motor vehicle accidents.

RESULTS: The analysis included 33 500 ED visits among the outcomes of interest (5717 children aged 0-17 years [17.1%] and 11 150 adults aged >65 years [33.3%]; 17 394 male [51.9%] and 16 104 female [48.1%]; 2829 Black [8.4%] and 22 537 White [67.2%]; 9256 Hispanic [27.6%]) and 206 dust-impacted zip codes. The strongest associations between dust storms and ED visits were found for asthma (lag 0-2 relative risk [RR], 1.06; 95% CI, 1.01-1.11; P = .03), culture-negative pneumonia (lag 0-7 RR, 1.06; 95% CI, 1.02-1.10; P = .002), CHF (lag 0-7 RR, 1.06; 95% CI, 1.01-1.10; P = .01), and motor vehicle accidents (lag 0 RR, 1.13; 95% CI, 1.04-1.23; P = .003). Associations of dust storm exposure with ischemic heart disease were mostly protective (eg, lag 0-2 RR, 0.89; 95% CI, 0.84-0.95; P < .001). Associations of dust storm exposure with risk of ED visits for CHF and motor vehicle accidents were robust against adjustment for ambient ozone (eg, CHF: RR, 1.08; 95% CI, 1.03-1.13; P = .003) and nitrogen dioxide (eg, CHF: RR, 1.08; 95% CI, 1.03-1.13; P = .003) air pollution.

CONCLUSIONS AND RELEVANCE: In this study, dust storms were positively associated with ED visits for asthma, pneumonia, heart failure, and motor vehicle accidents. These findings contribute to our understanding of the association of dust storms with morbidity in the US and potential outcomes under a changing climate.

PMID:39937479 | DOI:10.1001/jamanetworkopen.2024.57666

JAMA Netw Open. 2025 Feb 3;8(2):e2459188. doi: 10.1001/jamanetworkopen.2024.59188.

ABSTRACT

IMPORTANCE: The US has implemented several regulatory measures to govern the sale and marketing of electronic nicotine delivery systems (ENDS). A nicotine warning statement requirement became effective in September 2018, the minimum legal age for tobacco and nicotine sales was raised to 21 years (Tobacco to 21 Act [T21]) in December 2019, and a January 2020 enforcement policy limited the sale of cartridge-based ENDS to only tobacco and menthol flavors.

OBJECTIVE: To track the presence of the nicotine warning statement, youth appeals, and flavor cues in the advertisements of 3 ENDS brands with marketing authorization during the implementation of the US federal tobacco policies.

DESIGN, SETTING, AND PARTICIPANTS: In this qualitative study, a content analysis was conducted on ENDS advertisements in the market from November 18, 2015, to June 26, 2022. All mobile, online display, outdoor, and print advertisements from the 3 US ENDS brands with marketing granted orders as of June 2022 were collected through Vivvix, a commercial advertisement intelligence company. Advertisements were excluded if they targeted businesses rather than consumers, contained display errors that were unretrievable, or were duplicates. Data analysis was completed in March 2024.

EXPOSURE: The nicotine warning statement requirement, T21, and the flavor enforcement policy.

MAIN OUTCOMES AND MEASURES: Nicotine warning statement compliance and presence of youth-appealing features (eg, young models, sports, and sex appeal) and nonmenthol, nontobacco flavor cues (eg, images of food, characterizing words like sweet or fruity) in ENDS advertisements before and after policy implementation.

RESULTS: Of the 614 advertisements analyzed, the proportion containing the nicotine warning statement increased from 18 of 83 (21.7%) in the year preceding policy implementation to 147 of 152 (96.7%) in the subsequent year (χ21 = 144.5; P < .001). The proportion of advertisements containing any youth-appealing features increased from 35 of 171 (20.5%) in the year before T21 to 64 of 143 (44.8%) in the year after T21 (χ21 = 21.28; P < .001). There was no significant difference in flavor cues in the advertisements in the year before the flavor enforcement policy (30 of 161 [18.6%]) and those in the following year (38 of 149 [25.5%]) (χ21 = 2.13; P = .14).

CONCLUSIONS AND RELEVANCE: This qualitative study found immediate compliance with nicotine warning statements but no significant reduction in use of flavor cues and an increase in youth-appealing features in the first year after regulatory measures. The findings suggest a need for continued close monitoring of youth appeals in ENDS advertisements on all platforms to inform potential policies and interventions that can be used to counter the reach, appeal, and impact of these advertisements.

PMID:39937476 | DOI:10.1001/jamanetworkopen.2024.59188

JAMA Netw Open. 2025 Feb 3;8(2):e2459371. doi: 10.1001/jamanetworkopen.2024.59371.

ABSTRACT

IMPORTANCE: Over the past decade, the leadership of the National Institute of Mental Health (NIMH) has emphasized the importance of a transdiagnostic approach to psychiatric investigation using Research Domain Criteria (RDoC) mapping more closely to neurobiology.

OBJECTIVE: To investigate whether research support from the NIMH for individual RDoC domains and for transdiagnostic investigation has changed over time and has had differential impact in terms of publication, citations, or patent filings.

DESIGN, SETTING, AND PARTICIPANTS: In this longitudinal cohort study, all R01, R21, and R03 studies funded by the NIMH between January 2003 and December 2023 were identified via the National Institutes of Health RePORTER database. Their abstracts were characterized in terms of RDoC domains (negative valence, positive valence, cognition, social, arousal, and sensorimotor) using a large language model.

MAIN OUTCOMES AND MEASURES: Primary outcomes were publications, citation impact estimated at 5 years from the index year of funding, and patents, examined using regression models adjusted for other grant characteristics.

RESULTS: Among 8897 R01, R03, and R21 projects, reflecting $17.7 billion of investment, abstracts of 3141 (35.3%) reflected negative valence; 1344 (15.1%), positive valence; 2781 (31.3%), cognition; 1607 (18.1%), social; 343 (3.9%), arousal; and 571 (6.4%), sensorimotor domains. A total of 1793 (20.2%) incorporated a transdiagnostic perspective. Positive and social domains were associated with fewer publications (difference, -1.13 [95% CI, -2.11 to -0.15] and -2.23 [95% CI, -3.15 to -1.30], respectively) and lesser citation impact (difference, -0.47 [95% CI, -0.75 to -0.18] and -1.19 [95% CI, -1.46 to -0.91], respectively) at 5 years. Social (adjusted odds ratio [AOR], 0.11; 95% CI, 0.04-0.23) and cognitive (AOR, 0.66; 95% CI, 0.48-0.89) domains and transdiagnostic proposals (AOR, 0.37; 95% CI, 0.21-0.60) were associated with lower likelihood of patent filing.

CONCLUSIONS AND RELEVANCE: In this study of NIMH funding, grants reflecting different RDoC domains differed substantially in their scientific impact in terms of publications, citations, and patent generation. The findings suggest that large language models represent a promising approach to characterizing research proposals at scale, which may be useful in guiding resource allocation to maximize scientific return on investment.

PMID:39937475 | DOI:10.1001/jamanetworkopen.2024.59371

JAMA Netw Open. 2025 Feb 3;8(2):e2459554. doi: 10.1001/jamanetworkopen.2024.59554.

ABSTRACT

IMPORTANCE: The impact of Medicaid telehealth reimbursement policies on staffing and patient-centered care in the safety net are largely unknown but critical to successful and equitable access to telehealth.

OBJECTIVE: To identify and characterize federally qualified health center (FQHC) staff and leadership’s perceptions of the benefits and drawbacks of Medicaid telehealth reimbursement policies.

DESIGN, SETTING, AND PARTICIPANTS: This qualitative study used semistructured interviews conducted from April 2022 to January 2024 with snowballed sampled participants consisting of FQHC leadership, clinicians, and administrative staff in 6 FQHCs representing the 5 boroughs in New York, New York.

MAIN OUTCOMES AND MEASURES: Participants described telehealth experiences, including factors impending or contributing to staff turnover, patient satisfaction, and financial sustainability within FQHCs. Thematic analysis was used to analyze the data.

RESULTS: Of 56 interviews, 26 participants (46.4%) were part of the leadership team, 18 (32.1%) were clinical staff, 8 (14.3%) were program support staff, 7 (12.5%) were enabling services staff, 3 (5.4%) were site directors, and 3 (5.4%) were another staff category. Three overarching themes characterized staff and leadership understanding of the impact of Medicaid telehealth reimbursement policies on FQHCs: (1) Medicaid telehealth policy design was perceived to exacerbate a workforce shortage, particularly among mental health care practitioners; (2) patients ranged in preferences and ability to access telehealth while FQHCs struggled to attain resources for telehealth; and (3) FQHC leadership envisioned a productive hybrid model where telehealth complements on-site care. FQHC staff and leadership reported opportunities to improve compliance, no-shows, and workflows through telehealth, but improvements in funding policy, such as payment parity and more grants that can be used to address telehealth infrastructure (eg, Internet access, equipment, and literacy), are urgently needed.

CONCLUSIONS AND RELEVANCE: In this qualitative study, staff at FQHCs perceived the current telehealth Medicaid reimbursement policies in New York State as a factor that exacerbated inequities to accessing care, particularly for mental health needs. These findings indicate that although telehealth brings new opportunities to advance patient-centered care, there are serious challenges on the path toward equitable care because telehealth is not yet integrated into payment in a sustainable way.

PMID:39937474 | DOI:10.1001/jamanetworkopen.2024.59554

JAMA Surg. 2025 Feb 12. doi: 10.1001/jamasurg.2024.6922. Online ahead of print.

ABSTRACT

IMPORTANCE: Transvaginal surgery is commonly performed to treat pelvic organ prolapse. Little research focuses on how sexual function relates to clitoral anatomy after vaginal surgery despite the clitoris’ role in the sexual response.

OBJECTIVE: To determine how postoperative sexual function after vaginal surgery is associated with clitoral features (size, position, shape).

DESIGN, SETTING, AND PARTICIPANTS: This was a cross-sectional ancillary study of magnetic resonance imaging (MRI) data from the Defining Mechanisms of Anterior Vaginal Wall Descent (DEMAND) study. The setting comprised 8 clinical sites in the US Pelvic Floor Disorders Network and included the MRI data of 88 women with uterovaginal prolapse previously randomized to either vaginal mesh hysteropexy or vaginal hysterectomy with uterosacral ligament suspension between 2013 and 2015. Data were analyzed between September 2021 and June 2023.

EXPOSURES: Participants underwent postoperative pelvic MRI at 30 to 42 months (or earlier if reoperation was desired) between June 2014 and May 2018. Sexual activity and function at baseline (preoperatively) and 24- to 48-month follow-up (postoperatively) were assessed using the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire, International Urogynecological Association Revised (PISQ-IR). Clitoral features were derived from postoperative MRI-based 3-dimensional models.

MAIN OUTCOMES AND MEASURES: Correlations between (1) PISQ-IR mean, subscale, and item scores and (2) clitoral size, position, and shape (principal component scores).

RESULTS: A total of 82 women (median [range] age, 65 [47-79] years) were analyzed (41 received hysteropexy and 41 received hysterectomy). Postoperatively, 37 were sexually active (SA), and 45 were not SA (NSA). Among SA women, better overall postoperative sexual function (higher PISQ-IR summary score) correlated with a larger clitoral glans width (Spearman ρ = 0.37; 95% CI, 0.05-0.62; P = .03) and thickness (Spearman ρ = 0.38; 95% CI, 0.06-0.63; P = .02). Among NSA women, sexual inactivity related to postoperative dyspareunia correlated with a more lateral clitoral position (Spearman ρ = 0.45; 95% CI, 0.18-0.66; P = .002), and sexual inactivity related to incontinence/prolapse correlated with a more posterior clitoral position (Spearman ρ = -0.36; 95% CI, -0.60 to -0.07; P = .02) (farther from the pubic symphysis). Shape analysis demonstrated that poorer postoperative sexual function outcomes in SA women and sexual inactivity in NSA women correlated with a more posteriorly positioned glans, anteriorly oriented clitoral body, medially positioned crura, and lateral vestibular bulbs.

CONCLUSIONS AND RELEVANCE: Results of this cross-sectional study suggest that postoperative sexual function after vaginal surgery was associated with clitoral glans size, position, and shape. Results warrant prospective studies on surgery-induced changes in clitoral anatomy and sexual function.

PMID:39937459 | DOI:10.1001/jamasurg.2024.6922

Int J Clin Oncol. 2025 Feb 12. doi: 10.1007/s10147-024-02658-1. Online ahead of print.

ABSTRACT

BACKGROUND: Human epidermal growth factor receptor 3 (HER3), a tyrosine kinase belonging to the HER family, is a known target for cancer therapy; recently, an anti-HER3 antibody-drug conjugate (ADC) is developing. To understand HER3 expression in epithelial ovarian cancer (EOC), this study was conducted.

METHODS: We investigated the expression of HER3 in 202 patients with EOC using immunohistochemistry (IHC), and the association between HER3 expression, clinicopathological features, prognosis, and treatment timing.

RESULTS: Of all the cases, 55.4% had a HER3 IHC score ≥ 1 + . In particular, 78.0% of the patients with clear cell carcinoma (CCC) and 87.9% of the patients with mucinous carcinoma (MC) had a HER3 IHC score ≥ 1 + . Regarding clinicopathological features, early disease stage, feasibility of primary debulking surgery, no residual tumor, and low CA125 levels were more frequently observed in patients with a HER3 IHC score ≥ 1 + . Furthermore, a HER3 no-expression showed a significant association with a relatively short progression-free survival (PFS). And, for patients with mucinous carcinoma, those with a HER3 IHC score ≥ 1 + had poorer PFS and overall survival than those with a HER3 no-expression (no statistically significant difference). In addition, we analyzed HER3 expression at primary tumor and recurrence tumor in same patients. Thus, we observed the HER3 IHC score tended to change from 0 to ≥ 1 + in recurrence cases compared with primary cases.

CONCLUSIONS: These observations suggested that patients with MC, CCC and recurrence of all histological type may potentially benefit from future clinical trials of HER3-directed therapies.

PMID:39937426 | DOI:10.1007/s10147-024-02658-1

J Epidemiol Glob Health. 2025 Feb 12;15(1):23. doi: 10.1007/s44197-025-00344-7.

ABSTRACT

BACKGROUND: Many of the studies in causal inference using propensity scores relied on binary treatments where it is estimated by logistic regression or machine learning algorithms. Since 2000s, attention has been given for multiple values (categorical) and continuous treatments and the propensity score associated with such treatments is called generalized propensity score (GPS). However, there is scant literature on the use of count treatments in causal inference. Besides, effective sample size, after weighting, along with other methods has not been practiced for GPS model performance measure. The study was done with the aim of using count treatments in causal inference; select appropriate GPS and outcome models for such treatment and ordinal outcome.

METHOD: A family of count models and a generalized boosted model (GBM) were used for GPS estimation. Their performance was measured in terms of covariate balancing power, effective sample size and the average treatment effect after GPS-based weighting. Marginal structural modeling (MSM) and covariate adjustment using GPS were used to estimate treatment effect on ordinal outcome. Stabilized inverse probability treatment weighting was used for covariate balancing assessment. Monte Carlo simulation study at various sample sizes with 1000 replication and household survey data were used in the study.

RESULT: GPS was trimmed at 1% and 99% which gave better results as compared to untrimmed results. The generalized boosted model performed well both in simulation and actual data producing a larger effective sample size and smaller metrics when estimating average treatment effect on the outcome. The MSM was found better than GPS as a covariate in the outcome model.

CONCLUSION: It is important to trim GPS when it approaches zero or one without loss of more information due to trimming. Effective sample size after weighting should be used along with other methods such as correlation and absolute standardized mean differences for GPS model selection. GBM should be used for GPS estimation for count treatments. MSM is important for the outcome model when weighting GPS method is used. Finally, the number of antenatal care services had an increasing effect on the probability of age-specific childhood vaccination.

PMID:39937387 | DOI:10.1007/s44197-025-00344-7

Discov Nano. 2025 Feb 12;20(1):32. doi: 10.1186/s11671-025-04190-1.

ABSTRACT

A highly efficient and nontoxic material methylammoniumtin(II) iodideperovskite solar cell is proposed. This proposed solar cell uses CH₃NH₃SnI₃ as the absorber layer, TiO₂ as an Electron transport layer (ETL), Indium tin oxide as a buffer layer, and Copper(I) oxide as the hole transport layer (HTL). The device is simulated using the SCAPS-1D simulation tool. This study details the optimization of a set of parameters, including the defect densities and the thickness of the absorber layer. The proposed structure is highly optimized result of 31.73% of enhanced power conversion efficiency (PCE), a J_SC of 24.526 mA/cm² (short-circuit current), FF of 81.40% (fill factor), and a V_OC of 1.56 V (open-circuit voltage) is obtained through simulation process. Compared to previously reported works, the performance of the device has improved significantly due to better optimization. Along with this electrical characteristic temperature analyses, conductance voltage, capacitance-voltage, and bandgap analyses have also been carried out to examine the device’s efficiency and performance.

PMID:39937384 | DOI:10.1186/s11671-025-04190-1