Nevin Manimala

Mol Biol Evol. 2025 Oct 1;42(10):msaf211. doi: 10.1093/molbev/msaf211.

ABSTRACT

Orphan genes, which encode species-specific proteins, are common but are rarely investigated. The SARS-CoV-2 orphan gene, ORF10, has been understudied; in vitro work suggests it may modulate innate immunity. Whether ORF10 influences COVID-19 outcomes in humans remained unknown. Here, analyzing millions of SARS-CoV-2 genomes, we find ORF10 sequences are identical to ancestral Wuhan-Hu-1 haplotype. In all variants of concern, <5% of genomes carry any ORF10 mutation. Despite limited statistical power due to the sparsity of mutated sequences, four ORF10 mutations were associated with less severe clinical outcomes in COVID-19 patients: three affect protein structure, one alters RNA structural dynamics. No mutations were linked to increased severity. ORF10 transcript levels in humans and human models are conditionally discordant from other SARS-CoV-2 genes. ORF10 expression in A549 and 293T cells significantly perturbs oxidative phosphorylation gene expression, disrupts immune gene networks, and shifts expression of 14 novel human transcripts. ORF10 is present in multiple Betacoronavirus pandemicum strains, but absent from SARS-CoV-1-like strains. We propose that this strain-restricted orphan gene contributes to severe COVID-19 in humans, with implications for future therapeutic strategies. These findings underscore the importance of studying recently evolved, potentially overlooked, viral orphan genes as a standard approach in pandemic preparedness.

PMID:41092398 | DOI:10.1093/molbev/msaf211

J Orthop Trauma. 2025 Oct 14. doi: 10.1097/BOT.0000000000003098. Online ahead of print.

ABSTRACT

OBJECTIVES: To compare the incidence and severity of patellofemoral chondromalacia and its correlation with anterior knee pain following suprapatellar (SP) versus infrapatellar (IP) approaches for tibial intramedullary nailing.

METHODS: Design: Prospective, randomized controlled trial.

SETTING: Single-center study at a Level I Trauma Center.

PATIENT SELECTION CRITERIA: Patients aged between 18-45 years who presented with AO/OTA type 42 fractures from September 2020 to March 2024 were randomized into Suprapatellar (SP) and Infrapatellar (IP) groups. MRI at six months post-surgery assessed cartilage damage using the Modified Outerbridge Classification. Diagnostic knee arthroscopy was offered for further evaluation.

OUTCOME MEASURES AND COMPARISONS: The primary outcome was frequency and severity of chondromalacia assessed via MRI (Modified Outerbridge Classification) and diagnostic knee arthroscopy at six months. Secondary outcomes were correlation of MRI findings with knee pain (VAS score) and comparison of time taken for nail insertion with cartilage damage in the SP group.

RESULTS: Both groups had 30 patients each. In SP group, mean age was 33.7 years (range 18-45 years) and 83.3% were male while IP group had a mean age of 29.3 years (range 18-45 years) and 83.3% were male. 57 underwent MRI knee (SP: 28, IP: 29) and 16 underwent diagnostic knee arthroscopy (SP: 9, IP: 7). MRI detected chondromalacia in 46.4% in the SP group and 44.8% patients in the IP group; there was no significant difference (p-value 0.9). Arthroscopy revealed chondromalacia in all 9 (100%) patients who underwent diagnostic arthroscopy in the SP group as compared to 2 of 7 (28.6%) patients in the IP group (p-value 0.003). Correlation between chondromalacia grading on MRI and VAS scores at 6 months follow-up was significant (r=0.4, p-value 0.006). Time taken for nail insertion weakly correlated with presence of chondromalacia on MRI in the SP group but was not statistically significant (r=0.2, p-value 0.5).

CONCLUSIONS: No differences were found in the occurrence of patellofemoral chondromalacia seen on MRI between SP or IP nailing techniques. The SP approach demonstrated a higher frequency of patellofemoral chondromalacia on arthroscopic evaluation.

LEVEL OF EVIDENCE: Therapeutic Level I.

PMID:41092396 | DOI:10.1097/BOT.0000000000003098

JMIR Res Protoc. 2025 Oct 15;14:e77780. doi: 10.2196/77780.

ABSTRACT

BACKGROUND: Male adolescents have significant sexual and reproductive health (SRH) needs and, despite the existence of national guidelines, their SRH care receipt remains poor. Technology-based interventions have been shown to successfully support adolescents’ SRH; however, they have primarily focused on female individuals. To date, no such solutions support comprehensive SRH care delivery for male adolescents in primary care settings. Health-E You/Salud iTu (Health-E You) is a mobile web app that was originally designed for female youth and has proven to be effective in improving contraceptive care delivery and use. Adolescents access the app ahead of a clinic appointment, which contains initial screening questions, interactive knowledge items, and contraception decision support with tailored recommendations based on the users’ input. The app then provides clinicians with a summary of patients’ recommended SRH care.

OBJECTIVE: This study aims to adapt Health-E You for use with diverse groups of male adolescents presenting for care. This protocol describes the development, testing, and evaluation of Health-E You for male youth.

METHODS: This study consists of 2 stages. Stage 1 involves formative research, design, and user testing of Health-E You for male adolescents. Specifically, we implemented a youth-centered design process, using multiple rounds of qualitative data collection and engaging youth and clinician advisors to design the Health-E You app from April 2023 through April 2024. From May 2025, for approximately 6 months, we are conducting beta testing of the app with youth and its output with clinicians. Transcripts of interviews and focus groups from stage 1 will be analyzed using deductive and inductive thematic analysis to identify knowledge and skill gaps for the app to address as well as desired app features. Quantitative data will be analyzed using descriptive statistics. Stage 2 will involve a stepped-wedge cluster randomized controlled trial with 2752 participants in 8 primary care settings across the United States to assess the impact of Health-E You on sexually active male adolescents’ SRH care receipt and condom use. Data will be analyzed with an intention-to-treat approach using separate mixed models for each study outcome with a random intercept to reflect clustering of patients within clinics, adjusted for clinic size.

RESULTS: Results will include qualitative data on male adolescents’ and clinicians’ perspectives on SRH care receipt and delivery, respectively, and their preferences for app design. User testing will provide qualitative and quantitative data on the feasibility, acceptability, and usability of Health-E You in clinical settings. The efficacy trial will evaluate the extent to which the app improves SRH care receipt and condom use among sexually active male adolescents.

CONCLUSIONS: The findings from this study will inform future technology-based interventions for male adolescents and improve male adolescents’ SRH care receipt in primary care.

TRIAL REGISTRATION: ClinicalTrials.gov NCT06525064; https://www.clinicaltrials.gov/study/NCT06525064.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/77780.

PMID:41092393 | DOI:10.2196/77780

JMIR Pediatr Parent. 2025 Oct 15;8:e75310. doi: 10.2196/75310.

ABSTRACT

BACKGROUND: Health care digitalization and pediatric information and communication technology have facilitated the use of telemedicine and digital communication tools in pediatric practice, improving accessibility and efficiency. Meanwhile, artificial intelligence (AI) is emerging as a promising tool in medicine. However, the rapid adoption of these technologies has raised concerns regarding reliability and ethics.

OBJECTIVE: This study examines the level of digitalization in pediatric consultations and explores the perspectives of health care professionals (HCPs) on digital technologies in patient care, analyzing differences by age group, health care management, and institution type.

METHODS: An observational, cross-sectional survey was conducted among Spanish HCPs dedicated to pediatric care. Participants completed an 18-question web-based questionnaire evaluating their use of digital communication tools, perceptions of online health information, and opinions on AI in clinical practice. Statistical analyses compared responses across age groups, health care management type, and institution type.

RESULTS: A total of 495 pediatric specialists participated (female: 273/495, 58.2%; aged >45 y: 324/495, 69.8%). Most participants worked in urban settings (409/469, 87.2%), in primary care (243/313, 77.6%), and in the public sector (253/464, 54.5%). The telephone remained the most used communication channel (462/481, 96.1%), followed by email (290/481, 60.3%) and WhatsApp (139/481, 28.9%). Private-sector HCPs used digital platforms more frequently than public-sector HCPs, including email (136/206, 66% vs 135/247, 54.7%; P=.02), Instagram (23/206, 11.2% vs 5/247, 2%; P<.001), WhatsApp (105/206, 51% vs 26/247, 10.5%; P<.001), and Facebook (18/206, 8.7% vs 3/247, 1.2%; P<.001). Nearly all respondents (417/437, 95.4%) believed that parents were increasingly seeking health information online, yet a considerable proportion (158/458, 34.5%) reported that parents rarely consulted them about reliable sources. Overall, 85.4% (410/480) agreed that the internet and social media raise many questions among parents, while only 7.5% (35/465) believed that the information found is generally reliable. Nearly half of the participants (232/443, 48.5%) proactively suggested trustworthy digital resources, while 44.1% (211/443) did so only when asked. Younger respondents (P=.002), public-sector HCPs (P=.005), and primary care specialists (P=.004) were significantly more likely to offer this guidance, with scientific society resources being the most frequently recommended (402/430, 93.5%). We found that 78.6% (369/470) of participants were familiar with AI, with private-sector HCPs demonstrating greater knowledge than public-sector HCPs (P=.003). Overall, 59.6% (279/468) agreed that AI could significantly improve medicine, a view more commonly held by private-sector HCPs (P=.005). However, 94.8% (306/323) expressed ethical concerns, and 89.8% (422/470) wished to receive AI-related training.

CONCLUSIONS: The survey highlights the increasing use of digital communication tools in pediatric practice, with private-sector HCPs leading adoption. While AI is viewed as promising, ethical dilemmas remain, underscoring the need for training. Limited confidence in online health information highlights the importance of strengthening digital literacy among both HCPs and parents to optimize patient care.

PMID:41092390 | DOI:10.2196/75310

JMIR Form Res. 2025 Oct 15;9:e68733. doi: 10.2196/68733.

ABSTRACT

BACKGROUND: LGBTQ+ (lesbian, gay, bisexual, transgender, queer, and other diverse sexual and gender identities) young adults may experience discrimination based on their sexual and gender minority status, which results in LGBTQ+ population health disparities. Although the health effects of minority stress have been studied for more than 30 years, most research relies on retrospective and cross-sectional designs. These methods limit the ability to establish causal links and to capture the fluctuating and time-sensitive nature of stress responses. In contrast, ecological momentary assessment (EMA) and wearable sensors allow for real-time tracking of stress exposures and their resulting physiological effects, enhancing data accuracy and ecological validity.

OBJECTIVE: The EMA and sensor protocol of the Stress and Heart Study was developed to capture real-time physiological responses to minority stress experiences among LGBTQ+ young adults. This pilot study aims to evaluate the acceptability and feasibility of the Stress and Heart Study protocol.

METHODS: Participants who identified as LGBTQ+ between the ages of 18 and 30 years who reported experiencing LGBTQ+ discrimination in the past 30 days in a screening survey were invited to participate in a 2-week EMA and sensor study. Participants received 4 daily EMA surveys and one end-of-day (EOD) survey on their smartphones, assessing general and minority stress experiences, positive and negative emotional states, and substance use. Heart rate variability was continuously recorded using a wearable sensor. Upon completion, participants completed a short exit survey to evaluate their study experience and satisfaction.

RESULTS: Twenty participants aged 18 to 27 (mean 21.7, SD 2.6) years were enrolled, representing diverse sexual orientations (8 lesbian/gay, 2 bisexual, 4 pansexual, and 6 queer), gender identities (10 cisgender, 3 transgender, and 7 non-binary), and racial/ethnic backgrounds (9 non-Hispanic [NH] White, 5 Latinx, 2 NH Black, and 4 NH Asian). Participants completed 89.4% (1001/1120) of EMA daily surveys and 92.1% (258/280) of EOD surveys. On average, participants wore the sensor for 74.6% (SD 24%) of the expected time (179/240 hours). The overall EMA daily and EOD surveys completion rate was 89.9% (1259/1400), with individual participation ranging from 70% (49/70) to 98.6% (69/70). A total of 85% (n=17) of participants reported wearing the sensor daily. In the exit survey, all participants indicated that the study’s time commitment met their expectations. Additionally, 90% (n=18) of participants reported that the sensor was comfortable and that the EMA app was user-friendly, with appropriately timed questions.

CONCLUSIONS: This study supports the feasibility and acceptability of the Stress and Heart Study protocol using smartphones and wearable sensors to collect real-time data on minority stress experiences and physiological response. Further research is needed to validate the use of this protocol in larger observational and intervention studies aimed at addressing the adverse health impacts of minority stress among LGBTQ+ populations.

PMID:41092389 | DOI:10.2196/68733

Bioinformatics. 2024 Dec 26;5(1):vbaf230. doi: 10.1093/bioadv/vbaf230.

ABSTRACT

SUMMARY: Several approaches have been proposed to reconstruct interactions between groups of cells or individual cells from single-cell transcriptomics data, leveraging prior information about known ligand-receptor interactions. To enhance downstream analyses, we present an end-to-end dimensionality reduction workflow, specifically tailored for single-cell cell-cell interaction data. In particular, we demonstrate that sparse dimensionality reduction can pinpoint specific ligand-receptor interactions in relation to clusters of cell pairs. For sparse dimensionality reduction, we focus on the Boosting Autoencoder approach. Overall, we provide a comprehensive workflow, including result visualization, that simplifies the analysis of interaction patterns in cell pairs. This is supported by a Jupyter notebook that can readily be adapted to different datasets.

AVAILABILITY AND IMPLEMENTATION: https://github.com/NiklasBrunn/Sparse-dimension-reduction.

PMID:41092369 | DOI:10.1093/bioadv/vbaf230

Adv Sci (Weinh). 2025 Oct 15:e10189. doi: 10.1002/advs.202510189. Online ahead of print.

ABSTRACT

Metabolite concentrations vary by age and sex, yet age- and sex-specific metabolomic risk scores and biological ageing clocks for mortality prediction remain undeveloped. Nuclear magnetic resonance (NMR)-based metabolomic profiling is conducted in 209144 UK Biobank participants (12347 deaths) and 6820 from the German ESTHER study (804 deaths). Mortality risk scores are derived using least absolute shrinkage and selection operator (LASSO)-regularized Cox regression, and metabolomics-based mortality risk clocks (MetaboMR clocks) are constructed using elastic net regression in sex- and age-stratified subgroups (50-59 and 60-69 years). Models are trained in 70% of UK Biobank and validated internally (30%) and externally in ESTHER. 68 metabolites are significantly associated with 10-year all-cause mortality in both cohorts. 20, 18, 12, and 13 metabolites improved 10-year mortality prediction in younger and older men, younger and older women. Metabolite-augmented models improved c-statistics by 0.036-0.084 across subgroups. In the external validation set, each year of age acceleration is associated with an 8% and 9% higher 10-year mortality risk for MetaboMR clock1 and clock2. Sex- and age-specific metabolomic risk scores significantly enhance 10-year mortality prediction beyond traditional models. The MetaboMR clocks may serve as measures of biological ageing and support personalized risk stratification in clinical settings.

PMID:41092367 | DOI:10.1002/advs.202510189

Int J Surg. 2025 Oct 14. doi: 10.1097/JS9.0000000000003670. Online ahead of print.

NO ABSTRACT

PMID:41092365 | DOI:10.1097/JS9.0000000000003670

J Pharm Pharmacol. 2025 Oct 15:rgaf097. doi: 10.1093/jpp/rgaf097. Online ahead of print.

ABSTRACT

INTRODUCTION: Renal ischemia-reperfusion (RIR) induces inflammation, oxidative stress, and impaired renal function, partly through reduced nitric oxide (NO) availability. Rosuvastatin enhances NO production and has reported organ-protective effects. This study examined whether rosuvastatin confers renoprotection in RIR through NO-dependent mechanisms.

MATERIALS AND METHODS: Five groups of rats (n = 6) were used: control, RIR, RIR + rosuvastatin, RIR + rosuvastatin + L-NAME (NG-Nitro-L-arginine methyl ester), and RIR + rosuvastatin + L-arginine. Drugs were administered once daily from 3 days before ischemia until 24 h after reperfusion. Twenty-four-hour urine, blood, and kidney tissues were collected for analysis. Statistical tests were performed with Prism software.

RESULTS: Rosuvastatin significantly reduced serum urea and creatinine levels versus RIR alone. Glomerular filtration rate increased, though proteinuria remained unchanged. Inflammatory cytokines and oxidative stress decreased markedly, while tissue NO levels rose in the rosuvastatin group. L-NAME co-treatment diminished these effects, whereas L-arginine enhanced them, indicating NO involvement.

CONCLUSION: Rosuvastatin ameliorated renal injury in RIR, likely through activation of NO signaling. These findings suggest a potential therapeutic role for rosuvastatin in ischemic renal injury.

PMID:41092343 | DOI:10.1093/jpp/rgaf097

Microbiology (Reading). 2025 Oct;171(10). doi: 10.1099/mic.0.001616.

ABSTRACT

Consumers’ healthy lifestyle practices have heightened the appeal of minimally processed foods, especially the fermented kind. Kefir and nabeez with numerous benefits are world-famous beverages. This study aimed to explore the enterococcal and lactococcal probiotic strains associated with these beverages. Artisanal recipes were used to make kefir and nabeez, and bacteria were isolated using classical culturing techniques. The isolates were screened based on antimicrobial potential, safety and probiotic attributes. The bacterial isolates obtained from three fermented beverages, milk kefir, water kefir and nabeez, were assessed for safety concerns, and those deemed safe were tested for antagonistic potential. Strains of Enterococcus durans (NPL1395_MK, NPL1396_MK and NPL1480_MK), Enterococcus faecium (NPL1390_MK, NPL1420_WK and NPL1427_Nb) and Lactococcus lactis (NPL1426_Nb, NPL1428_Nb and NPL1436_Nb) demonstrated interesting antimicrobial characteristics against food-borne pathogens. Strains from milk kefir and nabeez could tolerate strong acidic and bile stress. All strains were susceptible to lysozyme and phenol at the concentrations tested but demonstrated significant antioxidant potentials, exopolysaccharide production and bile salt hydrolase activities. Cholesterol assimilation was most significant in milk kefir and nabeez strains, which also had good adherence and biofilm formation. Statistical analysis of performance data using the principal component analysis identified L. lactis strain NPL1428_Nb as the best. It exhibited good potential to persist in the human gut based on its ability to tolerate in vitro mixtures simulating the gastrointestinal tract digestive fluids, using the static digestion model. Therefore, strain NPL1428_Nb of traditional fermented beverage provenance has good prospects for use in probiotic product development.

PMID:41091549 | DOI:10.1099/mic.0.001616