Human Vaccines & Immunotherapeutics

Background. Although health mediation is widely studied in the U.S. through community health worker programs, evidence on their effectiveness in promoting cancer screening in Europe is limited. Since 2022, the "13 en Sante" program has implemented a multicomponent health mediation intervention -combining educational activities, outreach strategies, and navigation support- in socioeconomically disadvantaged neighbourhoods of Marseille, France. This study evaluates the effectiveness of this program in promoting breast, colorectal, and cervical cancer screening. Methods. A controlled before-after design based on two cross-sectional surveys was conducted in 2022 and 2024 in intervention or control neighbourhoods. Individuals aged 18-74 were randomly selected and interviewed via door-to-door questionnaires. Weighting was applied to account for stratified sampling and to align age and sex distributions with census data. Weighted logistic regression models were fitted for each cancer screening to estimate the intervention's effects on uptake and awareness at both individual and population levels. Findings. Overall, 4,523 individuals were included across the two cross-sectional surveys. The program successfully reached individuals facing cumulative socioeconomic barriers to healthcare access. No significant population-level effect was observed. At the individual level, declared exposure to health mediation was associated with significantly higher uptakes of breast and colorectal cancer screenings (breast: 54% vs 74%, OR=2.3 [1.1-4.5]; colorectal: 30% vs 50%, OR=2.8 [1.3-5.8]). In addition, colorectal cancer screening awareness was significantly higher among exposed participants (83% vs 93%, OR=8.1 [2.1-31]). Interpretation. This study provides the first evidence that a multicomponent health mediation intervention could effectively promote breast and colorectal cancer screening in disadvantaged French neighbourhoods. The study highlights screening-specific mechanisms of action that should be considered to further optimize intervention effectiveness. Funding. The survey was funded by the Regional Health Agency of Provence-Alpes-Cote d'Azur and Sante publique France.

Vaccination frequently elicits suboptimal immunogenicity in organ transplant recipients, particularly those on long-term immunosuppressive therapy, highlighting the need for improved understanding of immunosuppression mechanisms and optimized vaccination strategies. This study enrolled a cohort of 132 individuals and observed significantly lower antibody levels in kidney transplant recipients (KTRs) compared to non-transplant controls (non-KTRs). Antibody levels were inversely associated with both the dosage and duration of immunosuppressive therapy. Complementary small animal studies demonstrated that immunosuppressive treatment dosage-dependently and reversibly impaired antibody production, primarily by depleting immune cells, notably B cells. A single shot of adenoviral vector-based vaccines demonstrated enhanced immunogenicity relative to two shots of alum-adjuvanted protein vaccines, inducing potent neutralizing antibodies (NAbs) and a Th1-biased T-cell response even under continuous immunosuppression. The enhanced response was driven by reduced interference from pre-existing antibodies, sustained transgene expression, and the reprogramming of lipid metabolism to activate T and B cells. Our findings advocate for tailored vaccination strategies, positioning adenoviral vectors as a candidate modality for this vulnerable population.

Background: In low- and middle-income countries, the burden of hypertension is increasing. Medication adherence is a critical component of reducing hypertension-related cardiovascular disease (CVD) risk and death. There are many barriers to hypertension medication adherence, including challenges with access to and possession of medication. To address these challenges, we aim to implement a strategy in rural western Kenya that combines peer delivery of medications and health information technology to improve hypertension medication possession and adherence. Recognizing that stakeholder experience and knowledge can be useful to optimize successful implementation, we sought to assess micro- and macro-level stakeholder perceptions of the planned implementation strategy. Methods: Focus group discussions in both English and Kiswahili were conducted among people living with hypertension, community members, and health workers. In addition, key informant interviews were conducted with public sector health administrators including the program/policy planners for non-communicable diseases at the national and county levels. Content analysis of all transcripts was conducted. A codebook containing deductive codes was generated based on a priori themes identified from the interview guide. These included the perceptions of peers being involved in health service provision, medication delivery, psychosocial support, and the use of health information technology. Emerging themes were also identified and integrated into the results. The investigator team pooled codes according to conceptual alignment and integrated them into common themes after joint review and discussion. NVIVO 12 was used for the data analysis. Results:The PT4A implementation strategy was perceived to have both benefits and potential challenges. Major themes included the importance of trust resulting from a safe space to share experiences with peers, increased access to medications, improved hypertension management at the facility and community levels, and anticipated improved health outcomes for people living with hypertension. The success of the program was felt to rely heavily on the peers competency and how well they communicated, which was viewed as a potential challenge by some stakeholders. Areas of consensus expressed across all participant groups were mostly focused on patient psychosocial support and access to medications. Conclusion: This study was able to identify key perceptions elicited for an implementation strategy that combines peer medication delivery and health information technology to improve hypertension medication adherence. Pre-implementation stakeholder engagement can unearth unique perspectives around perceived benefits and challenges that can be used to refine strategies to increase the success of implementing evidence-based interventions in new contexts.

Background: Out-of-hospital cardiac arrest (OHCA) survival depends on timely bystander cardiopulmonary resuscitation (CPR) and quick defibrillation via automated external defibrillator (AED). However, access to CPR education and willingness to intervene are not equitably distributed. Within the Muslim community, intersecting religious identity, language, immigration-related concerns, and other social determinants of health may affect CPR/AED education, bystander response, and ultimately OHCA outcomes, underscoring the need for culturally responsive, faith-based training models. Methods: A survey based cross sectional study was conducted to evaluate the perceived barriers to emergency response and lay rescuer cardiopulmonary resuscitation (CPR). Individuals aged 13 years and older were recruited between January and June 2025 through convenience sampling at free, non-certification public CPR/AED classes, where participants self-reported demographic characteristics and barriers to calling 9-1-1 or initiating CPR. Analyses compared Muslim and non-Muslim participants using Fisher exact tests and multivariable logistic regression models adjusted for demographic and socioeconomic factors, with results reported as odds ratios (OR) and 95% confidence intervals (CI). Results: Of the 651 surveys collected, 33% of participants identified as Muslim, and 46% reported no prior CPR/AED training, with a higher proportion among Muslim respondents (57% vs 41%). Religion was significantly associated with some perceived barriers, with Muslim participants more likely to report law enforcement as a barrier to calling 9-1-1 (OR: 0.53 for non-Muslims vs Muslims, p=0.04) and less likely to report ?no problem? starting CPR (OR: 0.91, p=0.04). Race and gender also influenced barriers, with non-white and female participants more likely to report immigration status, language, cost, and concern for violence as barriers to initiating CPR or calling 9-1-1. Conclusion: Muslim participants were more confident in performing CPR, but reported less confidence in calling 9-1-1, revealing gaps in emergency response readiness. This emphasizes the importance of culturally adapted CPR/AED training that addresses specific barriers within faith-based communities and to strengthen all links of the chain of survival.

Background: Schistosoma mansoni is a leading cause of hepatosplenic disease in sub-Saharan Africa. Yet, associations with current Schistosoma mansoni infections and hepatosplenic organometry remain unclear in the context of widespread mass drug administration and co-endemic infections. Methods: From January to February 2024, we conducted a community-based, cross-sectional study nested within the SchistoTrack cohort in three districts of Uganda. Liver and spleen dimensions were assessed via point-of-care B-mode ultrasound for 3121 individuals. Organ dimensions were classified using the standard deviations from height-standardized internal reference values derived from an infection-free population. Multinomial logistic regressions were run for children (5-17 years) and adults (18+ years) separately. Population attributable fractions (PAFs) were used to estimate the proportion of abnormal organometry statistically attributable to each infection. Key exposures were S. mansoni, malaria, human immunodeficiency virus (HIV), and hepatitis B virus (HBV) alongside a comprehensive set of social, biomedical, and other covariates controlled for. Results: Moderate-to-severe splenic enlargement was observed in 29.1% (438/1507) of children and 23.3% (376/1614) of adults. Among adults, 20.9% (337/1614) had left liver lobe enlargement and 18.8% (303/1614) had right liver lobe shrinkage. In children, severe splenic enlargement was statistically attributable to malaria (PAF 46.7%; Relative Risk Ratio (RRR) 3.96, 95% CI 2.64-5.92) and S. mansoni infection intensity (PAF 23.6%; RRR 1.12, 95% CI 1.04-1.20). In adults, S. mansoni intensity was associated with moderate left liver lobe enlargement (PAF 12.4%; RRR 1.11, 95% CI 1.04-1.18). In adults, HIV was associated with severe left liver lobe shrinkage (RRR 4.50, 95% CI 1.19-17.00) and severe splenomegaly (RRR 3.62, 95% CI 1.58-8.33), while HBV was associated only with severe left liver lobe shrinkage (RRR 2.54, 95% CI 1.07-6.03). Praziquantel treatment in the past year showed inconsistent associations and no clear protective pattern. Conclusion: Current S. mansoni infection intensity remains associated with splenomegaly in children despite controlling for concurrent malaria positivity, and with hepatomegaly in adults despite HIV and HBV associations.

Background: Type 2 diabetes is a growing challenge in low- and middle-income countries, where health systems face major capacity gaps. Participatory learning and action (PLA) has shown effectiveness in preventing type 2 diabetes in Bangladesh, but little is known about its use in other LMICs for diabetes. The EMPOWER-D (Engagement of community through Participatory learning and action for cOntrol and prevention of type 2 diabetes) trial is testing PLA for diabetes prevention in communities in Pakistan and Afghanistan. This protocol describes the plans for the embedded process evaluation (PE). Methods: The PE will use a mixed-methods design across three sites, following the UK Medical Research Council framework for PE, examining implementation, mechanisms of impact and context. Implementation will be assessed using adaptation reports, fidelity checklists, attendance data, and supervisor reports. Mechanisms of impact will be explored through interviews, focus group discussions and photovoice. Contextual factors will be examined through interviews with participants, community mobilisers, supervisors, and key stakeholders. Quantitative data will be analysed descriptively, while qualitative data will undergo thematic analysis using a theory of change framework. Comparative analysis will identify common and context-specific influences. Discussion: This is the first multi-country PE of a PLA intervention for diabetes prevention to our knowledge, and the first in Afghanistan and Pakistan. The study will provide insights into how the intervention was delivered, how and why it worked (or did not work), and the contextual factors shaping outcomes. Findings will inform the adaptation and scale-up of participatory approaches for non-communicable disease prevention in resource strained setting health systems.

Introduction: Neurodegenerative diseases (NDDs) including Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and non-AD dementias share chronic neuroinflammatory mechanisms that contribute to neuronal injury and disease progression. While anti-inflammatory therapies (AITs) are associated with reduced neurodegenerative disease risk, knowledge regarding the impact of biological sex and treatment duration across multiple NDDs remains limited. Methods: We conducted a retrospective cohort analysis using a large propensity-score-matched population (n = 190,308; 95,154 treated vs 95,154 untreated) to evaluate associations between long-term AIT exposure and incidence of major NDDs. Disease-specific and combined outcomes were assessed across drug classes (NSAIDs, corticosteroids, immunomodulators), sex, age, and therapy duration. Results: AIT exposure was associated with a significantly lower risk of developing any NDD (RR = 0.47, 95% CI 0.43-0.48, p < .0001) and was equally effective in both sexes. Risk reduction was observed for each individual disease: AD (RR = 0.40), non-AD dementia (RR = 0.51), PD (RR = 0.43), MS (RR = 0.25), and ALS (RR = 0.48). Among drug classes, immunomodulators conferred the largest reduction (RR = 0.19), followed by corticosteroids (RR = 0.41) and NSAIDs (RR = 0.42). Duration analyses revealed a graded benefit, with RR declining from 0.94 (<1 year) to 0.25 (>6 years). Risk reduction was strongest in older participants (75-79 years). Discussion: Chronic use of anti-inflammatory or immunomodulatory therapies was associated with substantially reduced incidence of multiple neurodegenerative diseases in both sexes. The strongest effects were observed with immunomodulator use and prolonged therapy duration, suggesting that sustained modulation of systemic inflammation confers broad neuroprotective effects in both sexes. These findings highlight the potential of targeting immune-inflammatory pathways for neurodegenerative disease prevention and can inform prospective mechanistic and interventional studies.

Objective To test the effectiveness of a postpartum behavioural intervention delivered by automated text messaging in reducing weight. Design Two parallel group, multicentre, randomised controlled trial. Setting Recruitment from five areas across the United Kingdom (Belfast, Bradford, Stirling, London and Cardiff) through healthcare and community pathways, including social media. Participants A diverse sample of 892 women between 6 weeks and 24 months postpartum, aged 18 years or more and with a body mass index of 25 kg/m2 or more, enrolled between May 2022 and May 2023: 445 were randomised to the intervention and 447 to an active control (comparator). Interventions Twelve months of fully automated text messages with embedded behaviour change techniques and two-way messaging components to support weight loss and maintenance of weight loss in the postpartum period by targeting dietary, physical activity and weight management behaviours. The comparator group received 12 months of text messages on child health and development tailored to child age. Main outcome measures Primary outcome: weight in kilograms at 12 months (end of intervention). Secondary outcomes recorded at 6 and 12 months were changes in weight (at 6 months), body mass index, proportions of women with weight gain or loss of 5 kg or more, waist circumference, self-reported dietary intake, physical activity and infant feeding practices. Results 674 (75.6%) participants were included in the primary analysis. There was no statistically significant difference found in the adjusted mean weight change between the intervention and active control groups (-0.1 kg (95% confidence interval -1.0 to 0.8, P= 0.84). Sensitivity analyses did not change these results. There was a small statistically significant improvement in Fat and Fibre Barometer scores at 12 months in the intervention compared with control group (adjusted mean difference 0.09, 95% CI: 0.04 to 0.14; P <0.001) and a statistically significant increase in physical activity scores (International Physical Activity Questionnaire Short Form) at 12 months in the intervention group compared with the control group (adjusted mean difference 405.3 total MET minutes/week, 95% CI: 141.3 to 669.3; P= 0.003). Conclusions A 12 month automated, interactive behavioural weight management intervention delivered by text message did not support weight loss for postpartum women but did have a positive impact on diet and physical activity behaviours.

Abstract Background: Enhanced Recovery After Surgery (ERAS) optimizes perioperative management for colorectal cancer (CRC), improving short-term outcomes, but its impact on long-term outcomes remains inconclusive, supporting the need for this meta-analysis. This study evaluates the effect of perioperative ERAS (therapy-focused) on 1-, 2-, 3-, and 5-year postoperative survival in patients with CRC. Methods: We conducted a systematic review and meta-analysis following a pre-registered protocol in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Web of Science, Embase, Medline Ovid, and Cochrane Library Wiley were searched up to December 31, 2025, for clinical studies reporting long-term postoperative survival outcomes of patients with CRC undergoing ERAS implementation. Of 1,063 retrieved reports, 10 studies (5,876 patients) were included in Kaplan-Meier-based meta-analyses and eight studies (5,556 patients) in aggregated data meta-analyses. Data extraction was performed independently by two reviewers, with study quality and risk of bias assessed using the Newcastle-Ottawa Scale (NOS) and RevMan software. Effect sizes were pooled using fixed-or random-effects models according to heterogeneity, with cross-validation and subgroup analyses examining the influence of tumor stage and ERAS adherence. The pre-specified primary outcome was postoperative overall survival (OS) [&ge;]12 months, and the secondary outcome was disease-free survival (DFS). Results: ERAS significantly improved OS at 1 year (93.2%, 95% CI: 92.3-94.2 vs. 90.2%, 95% CI: 89.1-91.2), 2 years (86.7% vs. 81.3%), 3 years (81.1% vs. 72.4%), 5 years (70.9% vs. 60.6%) (all P<0.01). The pooled HR for mortality was 0.72 (95% CI: 0.63-0.83, P<0.01), indicating a 28% reduction in long-term mortality. Stage I-II tumors and ERAS adherence [&ge;]70% conferred the greatest benefits. DFS did not show a statistically significant improvement (HR=0.90, 95% CI: 0.68-1.19, P=0.45). Included studies were of moderate to high quality (NOS score 6-9). Conclusions: Perioperative ERAS significantly improves 1- to 5-year OS and reduces long-term mortality in patients with CRC, with the greatest benefits in early-stage disease and high adherence. These findings support ERAS as a critical component of comprehensive CRC care.

Introduction Heat waves are increasingly frequent and linked to higher mortality risks in Hong Kong. However, estimates of total excess mortality associated with heat waves remain unavailable. This study quantifies excess deaths associated with heat waves in Hong Kong from 2014 to 2023. Methods Daily age- and sex-specific mortality rates and population data were obtained from the Hong Kong Life Tables and Census and Statistics Department. Temperature data came from the Hong Kong Observatory, and relative risks were derived from local research. A Monte Carlo simulation was used to estimate heat-attributable deaths under different heat wave definitions, calculating total excess deaths and annualized death rates per 100,000 population. Results Between 2014 and 2023, heat exposure resulted in an estimated 1,455 (95% CI: 1,098-1,812) to 3,238 (95% CI: 3,234-3,242) excess deaths. In 2023, annualized excess death rates ranged from 2.95 (95% CI: 2.41-3.50) to 5.09 (95% CI: 5.07-5.12) per 100,000 people. Males and individuals aged 65 or older were disproportionately affected. Conclusion Over the 10-year study period, 1,455 to 3,238 excess deaths in Hong Kong were attributed to extreme heat. Heat waves now rank among the top ten causes of death in Hong Kong, with mortality rates comparable to diabetes. These findings underscore the need for urgent public health interventions to mitigate the impact of extreme heat.

From 2021 to 2025, MRSA emerged as a major multidrug-resistant pathogen in the study area. Among 545 S. aureus isolates, 67.2% were MRSA, disproportionately affecting children under five (26.5%) and males (55.5%). Case incidence more than doubled by 2025, suggesting rising transmission or resistance. Most isolates were hospital-associated (85.2%), predominantly from outpatients (88.5%), with middle ear discharge as the main source (67%). Gentamicin showed the highest susceptibility (72.1%), while penicillin G resistance was nearly universal (96.7%). The majority (93.4%) were multidrug-resistant, with high MARI values indicating widespread and likely inappropriate antibiotic use. These findings reflect a complex interplay between pathogen behavior, antimicrobial use, and healthcare practices. Increasing MRSA burden may stem from inadequate infection control, poor stewardship, or enhanced community transmission. Incorporating molecular typing could deepen understanding of strain diversity and resistance mechanisms to guide targeted interventions

We introduce PerTexP (Pertussis Time Exploration), an interactive modelling tool designed to investigate pertussis transmission dynamics and to support the evaluation of vaccination strategies and short-term projections. PerTexP allows users to explore and compare maternal, infant, and non-infant booster vaccination scenarios and to assess their potential impact on disease transmission, with a particular focus on the Italian epidemiological context. The tool is based on a discrete-time, stage-structured compartmental model with two age classes. By enabling rapid scenario-based analyses, PerTexP supports evidence-informed decision-making and provides transparent insights into how alternative vaccination strategies may shape pertussis dynamics. Combining accessibility, flexibility, and methodological rigour, PerTexP offers a practical resource for researchers and public health practitioners interested in exploring and comparing pertussis control strategies.

Background Persistent inequities in immunisation coverage, particularly among zero-dose and under-immunised children, continue to challenge Pakistan's Expanded Programme on Immunization. Weak feedback loop, inconsistent data quality, and limited real-time monitoring impede effective decision-making. This Implementation Research was conducted under the MAINSTREAM Initiative funded by Alliance for Health Policy and Systems Research (AHPSR) and supported by the Aga Khan Community Health Services Department and National Institutes of Health Pakistan to design, implement, and evaluate a digital monitoring and action planning tool to strengthen data-driven decision-making within routine immunisation systems. Methodology/Principal Findings A co-creation approach was employed to design a digital monitoring solution through inclusive consultations, key informant interviews, and focus group discussions with EPI Punjab at provincial and district levels. The solution included a customised mobile application for data collection and a Power BI visualisation dashboard to map low-coverage areas, identify drivers of dropouts and zero-dose children, and capture caregivers' information sources to inform targeted communication. The intervention was piloted in 60 households across six clusters of a Union Council of District Lahore. Advanced analytics identified reasons for non-vaccination and missed opportunities, generating tailored recommendations and practical plans for program managers. The analysis assessed acceptability, adoption, fidelity, and perceived scalability through field observations, system use, and stakeholder feedback. The co-developed digital tool enhanced visibility of coverage gaps through UC-level mapping, real-time dashboards, and structured action planning. Pilot testing in Lahore showed strong acceptability, ease of use, fidelity, and adaptability among managers, supervisors, and vaccinators. Scalability and sustainability potential were demonstrated, though barriers included leadership turnover, system fragmentation, workload pressures, and resource constraints. Conclusion The tool demonstrated feasibility to strengthen immunisation equity, accountability, and responsiveness. Co-creation with stakeholders enhanced ownership, operational relevance, and adoption, while complementing existing platforms. Sustainability will depend on effective integration, local ownership, capacity building, and accountability, while scalability requires interoperability, resource commitment, policy support, and alignment with existing workflows.

Understanding host susceptibility to Mycobacterium tuberculosis (Mtb) is critical for the development of new vaccines. Certain individuals "resist" becoming infected with Mtb despite intensive exposure; however, it is unknown whether there is a genetic basis for "resistance" to Mtb infection across populations. Here we conducted a genome-wide association study (GWAS) of resistance to Mtb infection by carefully characterizing exposure to TB patients among 4,058 close contacts in India, Brazil, and South Africa. 476 (12%) "resisters" remained free of Mtb infection despite substantial exposure to highly infectious TB patients. GWAS identified a novel chromosome 13 locus (rs1295104126) associated with resistance across the multi-ancestry meta-analysis. Comparing Mtb-infection to all uninfected contacts, irrespective of exposure, yielded a different locus on chromosome 6 (rs28752534), near the HLA-II region. These findings demonstrate a common genetic basis for resistance to Mtb infection across multi-ancestral cohorts with potential to elucidate novel mechanisms of protection from Mtb infection.

Background and objectives STXBP1-related disorder (STXBP1-RD), caused by pathogenic variants in the STXBP1 gene, is a rare neurodevelopmental condition, characterized by early-onset seizures, developmental delay, intellectual disability (ID), and prominent motor dysfunction. Despite the high prevalence of motor symptoms, systematic gait characterization remains limited. We therefore aimed to quantitively assess gait in individuals with STXBP1-RD. Methods In this cross-sectional study, we included ambulatory patients aged 6 years or older with genetically confirmed STXBP1-RD. Instrumented 3D Gait Analysis (i3DGA) was performed to objectively quantify gait. Functional mobility was assessed with the Functional mobility scale (FMS) and Mobility Questionnaire 28 (MobQues28). Caregiver health-related quality of life was evaluated using the PedsQL-Family Impact Module (PedsQL-FIM). We explored associations between gait, functional mobility, STXBP1-variant type and clinical features (ID, age at seizure onset, seizure frequency, age at onset of independent walking). Correspondence between i3DGA and the Edinburgh Visual Gait Score (EVGS), an observational gait assessment, was investigated. Results Eighteen participants were included. Compared to typically developing peers, individuals with STXBP1-RD had significantly reduced walking speed, step and stride length. Gait patterns were highly variable, with the most frequent pattern being an externally rotated foot progression angle (FPA), present in 11/18 participants. At home, 93.75% of the participants (16/18) walked independently, yet community mobility was more variable: 11/16 (68.75%) walked independently, 2/16 (12.50%) with aid and 3/16 (18.75%) used a wheelchair, indicating increasing limitations with distance and environmental complexity. Earlier acquisition of independent walking strongly predicted later unassisted ambulation at community level (p<0.001). Median MobQues28 score was 57.14% and median PedsQL-FIM score was 60.42%, indicating a moderate level of mobility limitations and reduced health-related quality of life of caregivers. EVGS was highly positive correlated with i3DGA (p= 0.001). Discussion Quantitative gait analysis in individuals with STXBP1-RD demonstrates heterogenous kinematic deviations, with an externally rotated FPA emerging as the most common pattern. Age at independent walking was a clinically relevant predictor of later functional mobility. EVGS showed strong correspondence with i3DGA and may offer a more practical, semi-quantitative assessment for broader use. These findings inform clinical decision-making and guide the selection of scalable outcome measures for natural history studies and interventional trials.

Background and Purpose: Magnetic resonance imaging (MRI) for radiation therapy treatment planning is currently being used in many anatomical sites to better visualize soft tissue landmarks, a technique known as an MRI simulation. A core component of modern MRI simulation configurations are the use of external laser positioning systems (ELPS) to help set up the patient. Though necessary for accurate and reproducible patient setup, the ELPS, if left on during imaging, may interfere negatively with image quality due to leaking electronic noise, of which MRI is sensitive to. It is currently unknown whether this leakage of electronic noise may further affect quantitative values derived from clinically employed relaxometric, diffusion, and fat fraction sequences. Therefore, in this study, we aim to characterize the impact of MRI simulation lasers on general image quality and quantitative imaging accuracy. Materials and Methods: First, a cine acquisition was used to visualize the real-time changes in image signal-to-noise ratio (SNR) from when the ELPS was deactivated to activated. To validate this effect quantitatively, the SNR was measured using the American College of Radiology (ACR) recommended protocol in a homogeneous phantom with the integrated body, 18-channel UltraFlex small, 18-channel UltraFlex large, 32-channel spine, and 16-channel shoulder coils. Next, a geometric distortion algorithm was tested in two vendor-provided phantoms while using the integrated body coil and the ACR Large Phantom protocol was tested. Finally, a series of quantitative MRI scans were performed using a CaliberMRI Model 137 Mini Hybrid phantom to validate quantitative T1, T2, and ADC while a Calimetrix PDFF-R2* phantom was used for quantitative PDFF and R2*. All scans were performed with both the ELPS both deactivated and activated. Results: Visible electronic noise artifacts were seen when using the integrated body coil when the ELPS was activated on the cine acquisition which led to a four-fold decrease in SNR using the ACR protocol. This SNR drop was not seen when using the remaining tested coils. The automatic fiducial detection algorithm was affected negatively by ELPS activation leading to misidentification when identified perfectly with the ELPS deactivated. Degradation in image intensity uniformity, percent signal ghosting, and low contrast object detectability was seen during ACR Large Phantom testing using the 20-channel Head/Neck coil. Concordance across quantitative MRI values was similar when the ELPS was both deactivated and activated while a consistent increase in standard deviation inside the ADC vials was seen when the ELPS was activated. Discussion: The extra noise induced from the activation of the ELPS during imaging should be avoided due to its potential to unnecessarily increase image noise. This is particularly true when conducting mandatory quality assurance testing for image quality and geometric distortion which utilize the integrated body coil which is most susceptible to ELPS-induced noise. Clear clinical guidelines should be implemented to make this issue known to the MRI technologists, physicists, and other relevant staff using an MRI with a supplementary ELPS for patient alignment.

Background Artificial intelligence (AI) is increasingly being integrated into healthcare systems, with growing applications in clinical decision support, workflow optimization, and population health management. While substantial investments have been made in digital infrastructure, the successful adoption of AI in primary care depends critically on the readiness, awareness, and educational preparedness of healthcare professionals. Global health authorities emphasize the need for ethically grounded and workforce-focused approaches to AI integration; however, evidence on clinicians readiness for AI, particularly in primary care settings and in the Middle East region, remains limited. Objectives This study aims to assess the level of awareness, perceptions, attitudes, and educational needs related to AI among healthcare professionals working within Qatars Primary Health Care Corporation (PHCC). In addition, it seeks to examine organizational factors influencing the integration of AI-focused education in primary care and to develop an AI readiness framework that can inform targeted training strategies and policy planning. Methods This study will adopt a mixed-methods design guided by the Organizational Readiness for Change (ORC) framework, adapted for AI integration in primary care. The quantitative component will consist of an anonymous, census-style online survey distributed to all healthcare professionals across PHCC health centers and headquarters, assessing AI awareness, attitudes, training needs, and perceived infrastructure readiness. Composite AI awareness and attitude scores will be calculated, and regression analyses will be used to explore factors associated with AI readiness. The qualitative component will include semi-structured interviews and focus group discussions using maximum variation sampling to capture diverse professional perspectives. Qualitative data will be analyzed thematically, following COREQ and SRQR reporting standards. Quantitative and qualitative findings will be integrated to generate an AI readiness profile and an actionable education roadmap aligned with national digital health priorities. Discussion This study will provide the first comprehensive assessment of AI readiness among primary care healthcare professionals in Qatar. By identifying knowledge gaps, training priorities, and organizational enablers and barriers, the findings are expected to inform the development of evidence-based AI education strategies within continuing professional development frameworks. The proposed AI readiness framework may also offer a transferable model for other health systems seeking to align workforce development with responsible AI implementation in primary care.

The use of semaglutide (SE), a glucagon-like peptide-1 receptor agonist (GLP-1RA) with glucose-lowering and weight-loss effects, has risen rapidly, particularly among women of reproductive age. While preclinical studies suggest benefits for ovarian function via the hypothalamic-pituitary-ovarian axis, its impact on the endometrial-embryo interface remains unclear. Here, we show that GLP-1R is dynamically expressed in fertile human endometrium, restricted to epithelial cells and markedly upregulated during the mid-secretory phase of the menstrual cycle. In a preclinical model of endometrial epithelial organoids, SE at physiological concentrations activates intracellular cAMP signaling, enhances epithelial metabolism, and upregulates receptivity markers without steroid hormone priming, whereas higher concentrations modestly reduce expression of a key receptivity marker PAEP/glycodelin and shift metabolism towards oxidative phosphorylation. By contrast, in stromal cells lacking detectable GLP-1R, SE disrupts decidualization, induces endoplasmic reticulum stress and suppresses cell-cycle at G2/M phase. Human embryo models, blastoids, expressed GLP-1R and underwent concordant SE-mediated transcriptional remodeling in epiblast and trophectoderm lineages, encompassing changes in metabolism and epigenetic regulation, but without shifts in lineage proportions. Notably, SE increased blastoid attachment to the endometrial epithelium in the absence of exogenous steroid hormones, suggesting enhanced epithelial-embryo interaction. Together, these findings reveal a compartment-specific mismatch, as SE augments epithelial and embryonic metabolic activity but compromises stromal support for implantation, with potential consequences for implantation due to stromal dysfunction.

Background: Quadriceps weakness may reduce sagittal plane shock absorption during landing, shifting load toward the frontal plane and increasing knee abduction moment (KAM), a biomechanical risk factor for anterior cruciate ligament (ACL) injuries. Purpose: The purpose of this study was to evaluate the association between isokinetic quadriceps strength and peak KAM during drop vertical jump landing in adolescent athletes. Study Design: Secondary analysis of previously collected data. Methods: Healthy adolescent athletes completed quadriceps strength testing using an isokinetic dynamometer and a biomechanical assessment during a drop vertical jump task. Quadriceps strength was quantified as peak concentric torque and the peak external KAM was calculated during the landing phase on the dominant limb. Both strength and KAM were normalized to body mass. Linear regression was used to examine the association between normalized quadriceps strength and peak external KAM on the dominant limb. Results: The association between quadriceps strength and peak normalized KAM on the dominant limb was not statistically significant ({beta} = -0.053 (95% CI [-0.137 to 0.030]), F(1,119) = 1.62, R2 = 0.013, p = 0.206). Quadriceps strength explained only 1.3% of the variance in peak KAM, indicating a negligible association between these variables in this cohort. Discussion: Quadriceps strength was not associated with peak normalized KAM during landing, suggesting that frontal-plane knee loading during a drop vertical jump is not meaningfully explained by maximal concentric quadriceps strength alone. KAM appears to be driven more by multi-joint movement strategy and neuromuscular coordination than by the capacity of a single muscle group.

Objectives: Compare Anterior Cruciate Ligament (ACL) Return to Sport after Injury (ACL-RSI) scores over time following ACL reconstruction (ACLR) between male and female patients aged 15 to 25 years with primary ACL injuries and ACL reinjuries. Design: Retrospective cohort design. Setting: Sports physical therapy clinics. Participants: 332 patients aged 15-25 years who underwent ACLR following either primary ACL injury or ACL reinjury, either contralateral or ipsilateral graft reinjury, and had at least one observation of the ACL-RSI. Main Outcome Measures: ACL-RSI score. Results: ACL-RSI scores significantly increased over time post- ACLR (p < .001), males reported significantly higher scores compared to females (p < .001), and patients with contralateral ACL reinjury demonstrated higher scores than those with ipsilateral ACL graft reinjury (p = .006), though there was no difference in scores between patients with primary ACL injury and ACL reinjury. A significant interaction effect of sex and injury status was also observed (p = .009), generally demonstrating that females had lower psychological readiness compared to males across injury statuses. Conclusions: ACL-RSI following ACLR varies based on biological sex and time post-ACLR, though ACL reinjury, independent of the reinjured leg, does not appear to effect scores compared to primary ACL injury.