Tag: nevin manimala

Clin Exp Dermatol. 2025 Sep 8:llaf407. doi: 10.1093/ced/llaf407. Online ahead of print.

ABSTRACT

BACKGROUND: Reflectance confocal microscopy (RCM) criteria for in vivo diagnosis of unperturbed basal cell carcinoma (BCC) lesions have been validated and studies have reported high diagnostic sensitivity. However, a paucity of data remains regarding preservation or changes in RCM features after biopsy or treatment.

OBJECTIVE: Prospectively image biopsy proven superficial BCC (sBCC) with RCM at baseline and 12 weeks post-treatment to determine clearance and identify any associated RCM features.

METHODS: Ten subjects with biopsy proven sBCC completed this study. Clinical examination, dermoscopy, and RCM imaging were performed at baseline, prior to treatment, and 12 weeks post treatment with a 1064 Nd-YAG laser. Following treatment, RCM features were compared to clinical and histologic findings.

RESULTS: Statistically significant changes in RCM features at baseline and follow-up included: tumor islands with hyperreflective aggregates, dark silhouettes, peripheral palisading, peritumoral clefting, and dermal inflammatory cells. Changes in nuclear streaming, fibrosis, and vasculature were not significant.

LIMITATIONS: A limitation of this study is the small sample size.

CONCLUSIONS: The features of nuclear streaming, fibrosis and dilated vessels may be observed during RCM imaging of biopsy proven BCC at baseline and post treatment, and should be cautiously interpreted. Additional studies are needed to further validate these findings.

PMID:40920911 | DOI:10.1093/ced/llaf407

Ann Am Thorac Soc. 2025 Sep 8. doi: 10.1513/AnnalsATS.202412-1265OC. Online ahead of print.

ABSTRACT

RATIONALE: Inflammation is central to chronic obstructive pulmonary disease (COPD) pathogenesis but incompletely represented in COPD prognostic models. Neutrophil to lymphocyte ratio (NLR) is a readily available inflammatory biomarker.

OBJECTIVES: To explore the associations of NLR with smoking status, clinical features of COPD, and future adverse outcomes.

METHODS: We analyzed NLR calculated from the complete blood count of participants who currently or formerly smoked (n = 2,624) and tobacco-naïve controls (n = 187) in the SPIROMICS multicenter observational cohort study. We assessed the stability of NLR at 6 weeks and 1 year, the association with select blood biomarkers, and the impact of smoking on NLR and cell counts. We stratified participants by NLR quartiles to compare cross-sectional clinical features at enrollment, prospectively observed exacerbations at 1 year, and mortality during longitudinal follow-up.

RESULTS: Higher NLR quartiles were broadly associated with more severe clinical features of COPD. NLR values were repeatable at 6 weeks (ICC=0.74) and 1 year (ICC=0.62). The impact of smoking on NLR varied with the severity of airflow limitation, mediated by an interaction between smoking, FEV1 % predicted, and neutrophil counts but not lymphocyte counts. The highest NLR quartile (>3.11) was associated with an increased risk of exacerbation over 1-year (adjusted OR=1.51 95%CI 1.18, 1.92) and increased risk of mortality (adjusted HR=1.41, 95%CI 1.20, 1.66) compared to quartiles 1-3.

CONCLUSIONS: Elevated NLR in stable COPD is a widely available biomarker associated with increased risk for exacerbation and death. The impact of cigarette smoking on NLR varies with disease severity.

PMID:40920896 | DOI:10.1513/AnnalsATS.202412-1265OC

PLoS Comput Biol. 2025 Sep 8;21(9):e1013370. doi: 10.1371/journal.pcbi.1013370. Online ahead of print.

ABSTRACT

A major goal of behavioural ecology is to explain how phenotypic and ecological factors shape the networks of social relationships that animals form with one another. This inferential task is notoriously challenging. The social networks of interest are generally not observed, but must be approximated from behavioural samples. Moreover, these data are highly dependent: the observed network edges correlate with one another, due to biological and sampling processes. Failing to account for the resulting uncertainty and biases can lead to dysfunctional statistical procedures, and thus to incorrect results. Here, we argue that these problems should be understood-and addressed-as problems of causal inference. For this purpose, we introduce a Bayesian causal modelling framework that explicitly defines the links between the target interaction network, its causes, and the data. We illustrate the mechanics of our framework with simulation studies and an empirical example. First, we encode causal effects of individual-, dyad-, and group-level features on social interactions using Directed Acyclic Graphs and Structural Causal Models. These quantities are the objects of inquiry, our estimands. Second, we develop estimators for these effects-namely, Bayesian multilevel extensions of the Social Relations Model. Third, we recover the structural parameters of interest, map statistical estimates to the underlying causal structures, and compute causal estimates from the joint posterior distribution. Throughout the manuscript, we develop models layer by layer, thereby illustrating an iterative workflow for causal inference in social networks. We conclude by summarising this workflow as a set of seven steps, and provide practical recommendations.

PMID:40920894 | DOI:10.1371/journal.pcbi.1013370

J Med Internet Res. 2025 Sep 8;27:e59976. doi: 10.2196/59976.

ABSTRACT

We estimated linear mixed-effects models to analyze changes in language patterns (as measured using Linguistic Inquiry and Word Count) among neurodiverse youth to introduce a novel assessment useful for research into the potential benefits of special interests while minimizing respondent and researcher burden.

PMID:40920452 | DOI:10.2196/59976

JMIR Res Protoc. 2025 Sep 8;14:e69212. doi: 10.2196/69212.

ABSTRACT

BACKGROUND: Fermented foods vary significantly by food substrate and regional consumption patterns. Although they are consumed worldwide, their intake and potential health benefits remain understudied. Europe, in particular, lacks specific consumption recommendations for most fermented foods.

OBJECTIVE: This project, which is under the framework of the Promoting Innovation Of Fermented Foods (PIMENTO) Cooperation in Science and Technology (COST) Action (CA20128), aims to develop a validated tool to quantitatively estimate fermented food intake across 4 European regions.

METHODS: The Fermented Food Frequency Questionnaire (3FQ) was designed to quantify fermented food intake in terms of frequency and quantity. Fermented foods were categorized into broad groups (eg, dairy, plant-based, meat, beverages) based on product classifications, ensuring that the foods included were genuinely fermented through ingredient analysis according to the International Scientific Association for Probiotics and Prebiotics consensus for fermented foods as a guide. For each main fermented food group, subcategories were determined after detailed discussions by a scientific expert panel that provided country-specific examples. For example, for hard cheeses, Parmigiano was chosen in the Italian version, and Graviera in the Greek version. The questionnaire was developed in English (universal version) and then translated into multiple languages using the back-translation method. Each version was pilot-tested for clarity, and data for the prospective validation were gathered. This included two key steps: (1) assessing repeatability by having participants retake the questionnaire after 6 weeks and (2) confirming accuracy by comparing 3FQ results against 24-hour dietary recalls from a subsample of participants. Statistical analyses will be used to confirm agreement between the methods. Representative sample calculations were performed for 4 groups by biological sex and age group (between 18 and 49.9 years and 50+ years). To ensure representative sample obtainment, participants aged 18+ years were recruited via the internet using multiple strategies, including social media platforms in all countries, snowball sampling, and potential supplementation with panels provided by the survey platform. Prior to all responses, participants were asked to provide informed consent and agree to data collection under ethical guidelines using a General Data Protection Regulation-compliant platform.

RESULTS: A representative sample of 1536 participants per European region was targeted, ensuring diversity in age and sex, with the goal of achieving a 60% response rate. A multilingual questionnaire was developed and pilot-tested for clarity. The upcoming steps will include final validation for accuracy and repeatability using 24-hour dietary recalls and specific statistical techniques of analysis to ensure reliability.

CONCLUSIONS: The validated web-based 3FQ aims to address the current gaps in fermented food intake to help improve future research in this important area.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/69212.

PMID:40920447 | DOI:10.2196/69212

JMIR Res Protoc. 2025 Sep 8;14:e50649. doi: 10.2196/50649.

ABSTRACT

BACKGROUND: Digital media frequently contains positive portrayals of alcohol content, which has been shown to be associated with alcohol-related cognitions and behaviors. Because youth are heavy media consumers and have access to unsupervised, repeat viewing of media content on their personal mobile devices, it is critical to understand the frequency of encountering alcohol content in adolescents’ daily lives and how adolescents engage with the content.

OBJECTIVE: This paper outlines the study protocol for examining adolescents’ exposure to alcohol-related content in digital media within their natural environments.

METHODS: Adolescents (N=302; 31.8% boys, 16.2% nonbinary, 51.3% girls; 25.8% Asian, 3.6% American Indian, 21.5% Black, 4.6% other, 52% White, 25.8% Hispanic or Latinx; mean age 16.21, SD 0.77 y) enrolled in high school were recruited through social media to participate in a prospective study involving bursts of ecological momentary assessment (EMA) reports coupled with longer surveys. We conducted group orientation sessions via videoconference and online surveys, followed by a 21-day EMA period that included scheduled reports across 4 daily time blocks, as well as self-initiated reports on media exposure. Reports of alcohol content exposure included details about the platform, level of engagement, source characteristics, beliefs and perceived norms about the content, the viewing context, and whether the content was sponsored or branded. The participants submitted exposures to alcohol content as an image (screenshot or photo) or text description to be objectively coded. The participants completed a weekly online survey assessing alcohol use and related cognitions. EMA reports will be merged with coded image and text entries and with data from baseline, weekly, and follow-up surveys. Self-reported alcohol exposure will be explored descriptively, and differences in exposure tested across subgroups. Event-level data will be compared with random prompt data to examine differences at times of exposure versus nonexposure. Prospective associations between media alcohol content exposure and alcohol use will be explored over 1-week and 4-month time frames. Mediation of the association between media alcohol exposure and drinking will be tested to explore putative mechanisms.

RESULTS: EMA data collection took place from February 2022 to August 2023. Data management and preliminary analysis are ongoing. Preliminary data were disseminated through conference presentations in 2024-2025 and manuscripts are ongoing with full results anticipated to be published in 2025-2026.

CONCLUSIONS: By characterizing adolescents’ real-world exposure to alcohol content in the media, the study provides critical information to develop and implement interventions to target youth behavior that are well suited to delivery via mobile devices. Next steps are to conduct focus groups to understand participants’ lived experience of exposure to media alcohol content and reactions to proposed intervention targets. This study and subsequent qualitative work will launch a program of research to counter the effects of alcohol-related media exposure as experienced by adolescents in an effort to minimize underage alcohol involvement.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/50649.

PMID:40920446 | DOI:10.2196/50649

JMIR Res Protoc. 2025 Sep 8;14:e64057. doi: 10.2196/64057.

ABSTRACT

BACKGROUND: Various media are used to enhance public understanding about diseases. While mobile health apps are widely used, there is little proof for using such apps to raise awareness of skin diseases.

OBJECTIVE: We intend to develop an app, called DEDIKASI-app, to raise awareness of skin diseases, including leprosy. The study will explore baseline awareness, assess the app’s acceptance by community members and health care workers, and evaluate its effectiveness in enhancing awareness about skin diseases.

METHODS: The study will be conducted in four phases: (1) development of DEDIKASI-app, (2) questionnaire development for an awareness study, (3) acceptability testing, and (4) effect measurement of DEDIKASI-app. We will adopt design thinking methodology to develop the app, involving systematic reviews, expert consultations, focus group discussions, and validation of the questionnaire on skin disease awareness. We will recruit 50 members of the community for the awareness and acceptability study and 1 health care worker per community health center to assess their perception of the app. A pilot study will assess the acceptability of DEDIKASI-app among community members and health care workers based on various constructs, with responses categorized as positive, negative, or undecided. The validity and reliability of a newly developed questionnaire on skin disease awareness will be tested, with validity results analyzed qualitatively and reliability measured using Cronbach α. The effectiveness of DEDIKASI-app in improving community awareness will be evaluated through a randomized controlled trial, using total scores, means, and SDs for control and intervention groups. Statistical significance of awareness level changes will be determined by delta change (P value), with P<.01 considered significant.

RESULTS: This study received ethical approval from the Ethics Review Board of the Faculty of Public Health, Universitas Airlangga (160/EA/KEPK/2023) and was registered in the Indonesia Clinical Research Registry (INA-O8EX278). Funding for the field research was secured in the period of May 2022-December 2024 from NLR Indonesia and Erasmus University Medical Center. As of manuscript submission, phase 1 (app development) and phase 2 (questionnaire development) have been completed. Data collection for the randomized controlled trial has just finished and data analysis is ongoing, with publication of the study results expected in late 2025.

CONCLUSIONS: Innovative approaches are required to enhance awareness in the community. This study will introduce new tools and insights to address the limited knowledge about detecting skin problems.

TRIAL REGISTRATION: INA-CRR Indonesia Clinical Research Registry INA-O8EX278; https://tinyurl.com/ms3k5yvn.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/64057.

PMID:40920442 | DOI:10.2196/64057

Rheumatology (Oxford). 2025 Sep 8:keaf478. doi: 10.1093/rheumatology/keaf478. Online ahead of print.

NO ABSTRACT

PMID:40920420 | DOI:10.1093/rheumatology/keaf478

JAMA Neurol. 2025 Sep 8. doi: 10.1001/jamaneurol.2025.3316. Online ahead of print.

ABSTRACT

IMPORTANCE: Exposure to fine particulate matter air pollution (PM2.5) may increase risk for dementia. It is unknown whether this association is mediated by dementia-related neuropathologic change found at autopsy.

OBJECTIVE: To examine associations between PM2.5 exposure, dementia severity, and dementia-associated neuropathologic change.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data associated with autopsy cases collected from 1999 to 2022 at the Center for Neurodegenerative Disease Research Brain Bank at the University of Pennsylvania. Data were analyzed from January to June 2025. Participants included 602 cases with common forms of dementia and/or movement disorders and older controls after excluding 429 cases with missing data on neuropathologic measures, demographic factors, APOE genotype, or residential address.

EXPOSURES: One-year mean PM2.5 concentration prior to death or prior to last Clinical Dementia Rating Sum of Boxes (CDR-SB) assessment was estimated using a spatiotemporal prediction model at residential addresses.

MAIN OUTCOMES AND MEASURES: Dementia severity was measured by CDR-SB scores. Ten dementia-associated neuropathologic measures representing Alzheimer disease, Lewy body disease, limbic-predominant age-related transactive response DNA-binding protein (TDP)-43 encephalopathy, and cerebrovascular disease were graded or staged. Linear, logistic, and structural equation models were used to examine the associations between PM2.5, CDR-SB, and neuropathologic measures, adjusting for demographic factors and APOE ε4 allele status.

RESULTS: In a total of 602 autopsy cases (median [IQR] age at death, 78 [71-85] years; 328 male [54.5%] and 274 female [45.5%]), higher PM2.5 exposure prior to death was associated with increased odds of more severe Alzheimer disease neuropathologic change (ADNC) (odds ratio, 1.19; 95% CI, 1.11-1.28). In a subset of 287 cases with CDR-SB records (median [IQR] age at death, 79 [72-86] years; 154 [53.7%] male and 133 female [46.3%]), higher PM2.5 exposure prior to CDR-SB assessment was associated with greater cognitive and functional impairment (β = 0.48; 95% CI, 0.22-0.74). Lastly, 63% of the association between higher PM2.5 exposure and greater cognitive and functional impairment was statistically mediated by ADNC (β = 0.30; 95% CI, 0.04-0.53).

CONCLUSIONS AND RELEVANCE: In this study, PM2.5 exposure was associated with increased dementia severity and increased ADNC. Population-based studies are needed to better understand this relationship.

PMID:40920417 | DOI:10.1001/jamaneurol.2025.3316

JAMA Intern Med. 2025 Sep 8. doi: 10.1001/jamainternmed.2025.4421. Online ahead of print.

ABSTRACT

IMPORTANCE: There is an unmet need for long-term, safe, effective, and hormone-free treatments for menopausal symptoms, including vasomotor symptoms (VMS) and sleep disturbances.

OBJECTIVE: To evaluate the 52-week efficacy and safety of elinzanetant, a dual neurokinin-targeted therapy, for treating moderate to severe VMS associated with menopause.

DESIGN, SETTING, AND PARTICIPANTS: OASIS-3 was a double-blind, placebo-controlled, randomized phase 3 clinical trial that was conducted at 83 sites in North America and Europe from August 27, 2021, to February 12, 2024, and included postmenopausal women aged 40 to 65 years who were seeking treatment for moderate to severe VMS (no requirement for a minimum number of VMS events per week). The data were analyzed on March 11, 2024.

INTERVENTION: Once-daily oral elinzanetant, 120 mg, or matching placebo for 52 weeks.

MAIN OUTCOMES AND MEASURES: The primary outcome was mean change from baseline to week 12 in the frequency of daily moderate to severe VMS, which was analyzed using a mixed model with repeated measures. Secondary end points included changes over 52 weeks in measures evaluating sleep disturbance and the effect on menopause-related quality of life. Exploratory end points included mean changes over 50 weeks in frequency and severity of daily moderate to severe VMS. Exploratory and secondary end points were analyzed using descriptive statistics. Safety was also assessed.

RESULTS: Overall, 313 women (mean [SD] age, 54.6 [4.7] years; 51 [16.3%] were Black or African American, and 240 [76.7%] were White individuals; 34 [10.9%] were Hispanic or Latina) were randomized to receive elinzanetant and 315 (mean [SD] age, 54.9 [5.0] years; 44 [14.0%] Black or African American, 34 [10.8%] Hispanic or Latina, and 253 [80.3%] White individuals) to receive placebo. At week 12, the mean change from baseline in daily moderate to severe VMS frequency was -5.4 (95% CI, -6.3 to -4.5) for elinzanetant and -3.5 (95% CI, -4.1 to -2.9) for placebo; the least-squares mean difference for elinzanetant vs placebo was -1.6 (95% CI, -2.0 to -1.1; P < .001). Although no statistical hypotheses were defined, nor was the study powered to detect between-group differences for the secondary and exploratory end points, descriptive analyses showed numerical advantages for elinzanetant vs placebo for improving VMS frequency and severity over 50 weeks and sleep disturbances and menopause-related quality of life over 52 weeks. Regarding safety, elinzanetant was not associated with hepatotoxic effects, endometrial hyperplasia, or meaningful changes in bone density or bone turnover markers. Treatment-related adverse events were more common with elinzanetant than placebo (30.4% vs 14.6%); the most frequent were somnolence, fatigue, and headache.

CONCLUSIONS AND RELEVANCE: The OASIS-3 randomized clinical trial expanded on findings from the 26-week OASIS-1 and OASIS-2 trials, exploring the use of elinzanetant over a longer duration and in a broader population. Elinzanetant shows promise as a treatment for moderate to severe VMS.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05030584.

PMID:40920404 | DOI:10.1001/jamainternmed.2025.4421