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461 papers

Virtual Reality Simulation in Postgraduate Pediatric Critical Care Training Based on Trainee Perceptions in London: Exploratory Mixed Methods Study.

Berlin AC et al. · Jun 25, 2026

Background Simulation-based training has established itself as integral to clinical education, particularly for high-stakes, low-frequency pediatric emergencies. Innovations incorporating virtual reality (VR) are rapidly gaining traction for offering scalable, repeatable, and immersive opportunities for scenario-based learning. Understanding its role and applicability in postgraduate pediatric training, however, remains limited, with further exploration required into how pediatric trainees perceive, conceptualize, and anticipate VR-based simulation within real-world training contexts. Objective This study explored London-based pediatric trainees' perceptions of VR simulation as an adjunct for developing skills in recognizing and managing critically ill children. Methods An exploratory mixed methods study was conducted among pediatric trainees across all training levels within the London School of Paediatrics between April 2024 and July 2024. Data were collected using a 35-item online questionnaire containing Likert-scale, categorical, and open-ended questions, alongside virtual semistructured interviews. The questionnaire explored current training practices; confidence and preparedness in managing critically ill children; familiarity and experience with VR; and perceived benefits, limitations, barriers, and facilitators to adoption. Quantitative data were analyzed descriptively, with exploratory Mann-Whitney U tests and Spearman correlations where appropriate. Internal consistency of key domains was assessed using Cronbach α. Qualitative data from open-ended responses and interviews were analyzed thematically using the Braun and Clarke reflexive approach. Quantitative and qualitative strands were integrated at the interpretation stage to contextualize survey patterns with illustrative qualitative insights. Results Thirty trainees participated in the survey (30/450, 6.7%; female: 16/30, 53%), with participants spanning all 8 training years. Two senior trainees participated in interviews. Clinical exposure or experience and simulation training were identified as central to developing skills in managing pediatric emergencies. Trainees also described limited exposure to high-acuity scenarios; variable access to high-fidelity simulation; and constraints related to workload, supervision, and feedback. Most participants (21/30) had no prior VR exposure in a medical setting, while 17% (5/30) had used VR training, and all reported positive experiences. Despite limited exposure, 93% (28/30) of participants were willing to try VR simulation for exposure to rare scenarios, structured decision-making, and confidence-building. Key perceived barriers included high cost (24/30, 80%), technological literacy (17/30, 57%), infrastructure (15/30, 50%), and limited stakeholder familiarity or support (25/30, 83%). Participants suggested taster sessions, faculty advocacy, leadership engagement, and phased implementation as potential facilitators. Internal consistency of attitudinal survey items was good (Cronbach α=0.80). Conclusions Despite limited exposure, pediatric trainees viewed VR simulation as a valuable adjunct to existing critical care training, particularly for those in earlier stages of training. However, these findings represent anticipatory perceptions rather than evidence of educational effectiveness. The implementation of VR will depend on addressing key infrastructural, organizational, educational, and equity-related barriers. Further multicenter studies are needed to evaluate the educational impact and feasibility, learning outcomes, and cost-effectiveness in postgraduate pediatric critical care training programs.

Medicine

Augmented Reality-Assisted Training Tool for Mental Health Task-Sharers: Pilot Mixed Methods Usability Study.

Ngiam LLV et al. · Jun 25, 2026

Background The growing global mental health (MH) burden, especially in underresourced communities, calls for innovative, scalable, and culturally responsive training approaches to expand care access and improve outcomes. Task-sharing has shown promise in addressing workforce shortages but is limited by training and supervision challenges. Traditional methods, such as role-playing and standardized patients, are resource-intensive and less scalable. Virtual simulations, including augmented reality (AR), present novel opportunities for immersive and interactive training. An AR-assisted training tool can enable culturally sensitive training while fostering empathy, communication skills, and confidence in handling nuanced MH scenarios. However, AR's usability and effectiveness for MH task-sharing training remain underexplored. Objective This study aimed to assess the usability of an AR-assisted MH task-sharing training tool that uses virtual patient (VP) simulation and evaluate its potential to enhance training. Additionally, we developed design recommendations for future related XR-assisted clinical training tools. Methods We conducted a formative, explorative sequential mixed-methods usability study. A convenience sample of 5 MH trainees or workers (ages 18-60 years; female: n=3, male: n=2; identifying as African American, Asian, and Hispanic) participated. Participants were recruited through a university-affiliated MH training program. The usability testing protocol included a semistructured prestudy interview, orientation to the AR headset (Magic Leap 2), a think-aloud user testing session, and a poststudy quantitative questionnaire and qualitative interview. Usability was assessed using a modified Post-Study System Usability Questionnaire (PSSUQ), which measures system usefulness, information quality, and interface quality. Data were analyzed using descriptive statistics and thematic analysis. Results The AR simulation was positively received by participants, demonstrating above-average usability. The overall mean PSSUQ score was 3.46 (SD 1.71), with subscale scores for system usefulness (mean 3.46, SD 1.77), information quality (mean 3.76, SD 1.73), and interface quality (mean 2.83, SD 1.59). Thematic analysis highlighted high realism fostered trainees' empathy toward the VP, while increasing immersion and interaction quality. Despite some hardware limitations and user discomfort that broke immersion, participants recognized the tool's potential and usefulness for training in various MH scenarios. Based on these findings, we proposed design recommendations across environmental context, training structure, VP behavioral realism (body language, voice, eye movement, and technical hardware considerations). Conclusions This pilot study is among the first to evaluate AR-based VP simulation for training lay MH task-sharers, filling the technology and population gaps of prior VR- and desktop-focused simulation research. Preliminary empirical usability evidence from a validated instrument (PSSUQ) demonstrates above-average usability, and findings informed design recommendations for future research. These findings suggest AR-based training could provide a less resource-intensive solution for realistic MH training practice in underresourced settings. Further research includes larger sample sizes for inferential analysis, comparison studies with traditional methods, and generalizing to other MH conditions.

Psychology

Real-World Evidence Assessment of the Risk of Nonfatal Stroke in Patients Prescribed SGLT2 Inhibitors.

Ayers AT et al. · Jun 25, 2026

Aims Use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in adults with Type 2 diabetes (AwT2D) has recently been associated with decreased stroke risk. In this study, we investigate the impact of SGLT2i on stroke. Materials and methods We conducted a cohort study using an electronic health record (EHR) representing 66 million patients to examine whether AwT2D have a lower incidence of stroke and/or transient ischemic attack (TIA) if treated with SGLT2i. All analyses were completed utilizing high-dimensional propensity score matching to control for confounders. Results AwT2D treated with SGLT2i compared to other antidiabetic medications, assessed after 1 year, starting 2 weeks after the date of prescription of SGLT2i or other antidiabetic drug, had a significantly lower incidence of any stroke (Odds Ratio (OR): 0.84 with 95% Confidence Interval (CI) 0.79-0.91, p p p = 0.005), and TIA (OR: 0.87 with 95% CI 0.80-0.95, p = 0.003). Conclusion Among AwT2D, those treated with SGLT2i had lower incidence of stroke and TIA compared with adults treated with other antidiabetic medications.

Medicine

Adenosquamous carcinoma of the lung: Comparative CT and pathological features versus adenocarcinoma and squamous cell carcinoma.

Yuan Q et al. · Jun 24, 2026

Objective Adenosquamous carcinoma (ASC) of the lung, containing both adenocarcinoma (AC) and squamous cell carcinoma (SCC) components, is associated with aggressive behavior and poor prognosis. Due to overlapping imaging features with AC and SCC, its preoperative diagnosis remains challenging. This study aimed to compare CT and pathological characteristics among ASC, AC, and SCC; identify key differentiators. Methods This retrospective study included 27 patients with pathologically confirmed ASC who underwent surgical resection from November 2018 to January 2025. Forty cases each of AC and SCC, matched for age, sex, and smoking history, were selected for comparison. Clinical, radiological, and pathological features were analyzed. Variables with statistical significance (P  Results Compared with SCC, ASC lesions were more peripheral and associated with higher distance ratios (DR), pleural retraction, spiculation, and lymph node metastasis (LNM). Compared with AC, ASC tumors were larger, more often solid, and exhibited lobulation, bronchial cutoff sign, and advanced staging. Among the evaluated analyses, the combined pathology-imaging approach showed the highest discriminatory performance, with AUCs of 0.909 (ASC vs SCC) and 0.900 (ASC vs AC). LNM and DR were more strongly associated with ASC relative to SCC, whereas larger tumor size, ill-defined margins, and advanced stage were more strongly associated with ASC relative to AC. Conclusion Certain CT imaging features, especially DR and LNM, were associated with ASC and may provide useful information for preoperative radiological assessment and subtype stratification.

Medicine

Uncovering the genetic basis of crown rust resistance in a northern-by-southern oat biparental population.

Sapkota S et al. · Jun 24, 2026

Crown rust, caused by the fungal pathogen Puccinia coronata f. sp. avenae (Pca), is a destructive foliar disease of oat. Use of host resistance is the preferred method of disease management. However, frequent emergence of new Pca races has hindered crown rust management in oat. Identification and deployment of non-race-specific genetic resistance will aid oat breeding efforts to develop germplasm with durable crown rust resistance. To map and characterize crown rust resistance, a recombinant inbred line (RIL) population was developed from a cross between LA07065_SBSBSB_32-2 and CDC Dancer and evaluated for crown rust reaction in four field environments for two years. The RIL population was genotyped using the oat 6K Infinium iSelect single nucleotide polymorphism (SNP) array and a total of 956 polymorphic SNP markers were used to construct the linkage map. Quantitative trait loci (QTL) mapping detected a total of six QTL on chromosomes 2D, 4A, 7A, 7C, and 7D influencing crown rust resistance. Two of these QTL were validated using genotype-phenotype association analysis in an independent set of oat lines. The identified QTL demonstrated additive effects on crown rust resistance within the RIL population. A major QTL on chromosome 7C, QPca-ars-7C, was detected consistently across environments and explained up to 16.54% of the phenotypic variation. Markers linked to QPca-ars-7C, and other QTL detected in this study have the potential to be used in marker-assisted selection for crown rust resistance.

Agricultural and Biological Sciences

Proteomics risk scores and mortality in heart failure: Generalizability across populations.

Shearer JJ et al. · Jun 23, 2026

Background Heart failure (HF) is a complex syndrome with high mortality. Proteomics risk scores have shown promise in predicting mortality beyond guideline-recommended clinical tools. It is crucial to understand how risk scores generated by different methods and populations perform, and whether they highlight the same protein targets relevant to outcomes. Methods To examine whether the study design impacts proteomics scores designed to predict mortality in HF, we evaluated three published risk scores that used the SomaScan assay to measure plasma proteins in a community cohort, clinical trial, and registry. Each score was assessed in the aforementioned community cohort and Cox models examined the association of a 1-standard deviation increase in score with mortality, with and without adjustment for clinical covariates. Performance of each risk score to predict 5-year mortality risk was assessed using calibration plots and time-dependent area under the curve and compared with a clinical model. Results Risk scores were similarly distributed and moderately correlated (Pearson correlation coefficient = 0.59-0.76). A 1-standard deviation increase in each risk score was associated with an increased risk of all-cause mortality: community cohort (HR = 2.70, 95% CI: 2.50-2.91); clinical trial (HR = 1.76, 95% CI: 1.65-1.88); registry (HR = 1.70, 95% CI: 1.6-1.81). Risk remained after adjustment for clinical covariates, although slightly attenuated, and similar across different ejection fraction categories. All risk scores showed strong calibration across the risk levels, alone, with an average expected over observed ratio ranging between 0.96-1.56. Seven proteins were included in at least two risk scores, with renin being included in all three. Conclusions All three proteomics risk scores improved risk stratification in HF patients beyond guideline recommended clinical tools, independent of study design and ejection fraction. These results demonstrate that proteomics risk scores can enhance risk stratification across the HF syndrome, even when derived from different methods and populations.

Chemistry

Towards modeling phage therapy.

de Boer RJ et al. · Jun 22, 2026

Patients infected with life-threatening multi-drug resistant (MDR) bacteria have been treated with cocktails of bacteriophages. This is a complicated form of personalized medicine as the phages given to a patient have to be selected beforehand on the basis of their lytic capacity of the infecting bacteria. Because bacteria rapidly become resistant, the evolution of resistance to a diverse cocktail of phages is a complicated dynamical process, during which competing bacterial strains replace one another by accumulating several resistance mechanisms, each of which may involve a fitness cost. As a consequence, it is typically not known why a particular phage therapy succeeded or failed, and how one can optimize the composition of the cocktails to maximize the rate of success. To improve upon this, we extend an existing in vivo-calibrated mouse model into a novel mathematical model for the human situation, and include multiple phages infecting multiple bacterial strains, differing in their resistance to each of the phages. We adjust several parameter estimates of the bacterial model to the human situation, and use the model to describe a successful case of phage therapy involving several cocktails, each containing several phages. In the model, treatment success crucially depended on pretreatment resistance levels, and on the diversity and the timing of the cocktails. Once an appropriate cocktail is found, it is less important to further optimize the infection rates of the phages. Resistant bacterial strains expand rapidly when sensitive strains decline, and the higher the infectivity of the phages, the faster resistant strains expand. Because resistance evolves rapidly, it is best to provide a diverse set of phages right from the start of therapy, i.e., to hit hard and early, and create a high genetic barrier to bacterial resistance.

Environmental Science

Identification of proteins exhibiting in vitro RNA chaperone activity through gradient profiling in the Lyme disease spirochete, Borrelia burgdorferi.

Van Gundy T et al. · Jun 18, 2026

RNA-binding proteins (RBPs) play key roles in regulating gene expression across all domains of life. However, relatively few RBPs have been discovered and characterized in Borrelia ( Borreliella ) burgdorferi , the causative agent of Lyme disease. We utilized gradient profiling to identify putative RBPs that co-sediment with small RNAs (sRNAs) and nascent mRNAs. The previously hypothetical proteins BB0749, BB0713 and BB0796, as well as the chemotaxis-related protein CheY2 and the flagella-associated protein FlgV demonstrated RNA unwinding (structural remodeling), RNA annealing, and strand displacement activity. Moreover, in vivo co-IP assays demonstrated BB0749 binds RNA in B. burgdorferi .

Immunology and Microbiology

Association between deployment and Gulf War Illness and adverse COVID outcomes in a nationwide cohort of 1990-1991 Gulf Era war veterans in the VA's Million Veteran Program.

White DL et al. · Jun 15, 2026

Background U.S. military veterans deployed to the Persian Gulf to serve in the 1990-1991 Gulf War (GWVs) have expressed concerns about potential increased risk of experiencing adverse COVID-related health outcomes given broad near-unique exposure to multiple diverse toxic agents during deployment and ongoing ~30% prevalence of Gulf War Illness (GWI+), a chronic, medically unexplained multi-symptom disorder associated with inflammation and immune dysregulation. Methods We conducted a retrospective study in the largest nationwide research cohort of 1990-1991Gulf War era veterans (GWEVs) enrolled in the VA's nationwide Million Veteran Program (MVP) to interrogate: 1) if deployed GWVs had increased risk for testing positive for novel SARS-CoV-2 infection (COVID+), COVID-related hospitalization, ICU admission, or death in 2020 (pre-vaccine period); and 2) if deployed GWVs with GWI+ had particularly increased susceptibility. COVID outcomes ascertained using VA's COVID Data Resource; GWI+ determined using CDC severe criteria in surveyed GWV subcohort. Findings Our overall GWEV cohort (N = 136,868) had mean age 60.7 years, with 84% male, 27% African-American, and 22% deployed; n = 26,141 COVID-tested in 2020. COVID test-positivity (COVID+) was slightly higher in deployed GWVs (18.8% vs. 17.2% in non-deployed GWEVs, p = 0.005). In multivariable logistic models, there were neither strong nor significant associations between deployment and testing COVID+, COVID-related hospitalization or ICU admission (adjusted [adj] ORs ranged from 0.90-1.06, all p-values >0.05), nor significant differences in COVID-related mortality. Preliminary analysis in our pre-pandemic surveyed deployed GWV subcohort (N = 1,643 COVID-tested, 39% GWI+, 18.4% testing-COVID+, 10.6% COVID+ hospitalized) suggested GWI+ potentially associated with significantly increased COVID-hospitalization risk (adjOR=2.21, 95%CI: 1.02-4.81, p = 0.04); though no significant excess was observed for COVID-related ICU admission or mortality. Conclusions Our findings demonstrated that overall deployment to serve in the 1990-1991 Gulf War was not associated with increased COVID-related health risks among Gulf War era veterans using VA healthcare system in early pre-vaccine pandemic era. Preliminary findings suggesting association between Gulf War Illness and potential increased COVID-related hospitalization risk among deployed Gulf War veterans in the early pandemic era warrants replication and ongoing evaluation to assess if it persists in the era of COVID vaccination, oral anti-COVID medications and new viral variants.

Medicine

Utility of sentinel surveillance as an early warning system for emerging pathogens in a low-resource setting: Correlations of dengue, chikungunya, Zika, and COVID-19 trends between sentinel and passive surveillance systems in Puerto Rico, 2012-2023.

Hernandez-Romieu AC et al. · Jun 12, 2026

The representativeness and timeliness of sentinel surveillance for endemic and emerging arboviral and respiratory diseases in low-resource settings are understudied. We compared laboratory-confirmed epidemic dengue, non-epidemic dengue, Zika, chikungunya, and COVID-19 (pre-Omicron and Omicron periods) cases reported in Puerto Rico's Sentinel Enhanced Dengue Surveillance System (SEDSS) with island-wide trends reported by the Department of Health's passive disease surveillance system (PADSS). We plotted trends over time to assess representativeness and used lagged cross-correlations to determine whether SEDSS reporting preceded PADSS. SEDSS trends were representative of island-wide trends for all pathogens. SEDSS preceded reporting in PADSS by up to three, eight, and two weeks for epidemic dengue, Zika, and pre-Omicron COVID-19, respectively. Increasing case trends for chikungunya occurred at broadly similar times in both systems, while temporal concordance was lower for non-epidemic dengue. In Puerto Rico, sentinel surveillance was representative of island-wide trends and could provide early warning for dengue epidemics and emerging diseases, such as Zika and COVID-19.

Medicine