Addiction Biology

Deficits in inhibitory control are common across a wide range of psychiatric disorders and are closely linked to symptom severity, including emotional dysregulation, anxiety, substance misuse, and self-harm, making them an appealing target for intervention. Cognitive training offers a low-cost, scalable, and non-invasive strategy to strengthen inhibitory control; however, most existing paradigms target only a single facet of inhibition and rarely account for environmental influences, such as affective context. To address these gaps, we developed a computerized inhibitory control training paradigm to simultaneously engage three components of inhibition: preemptive, proactive, and reactive, while embedding trials within positive and negative affective contexts to assess the impact of emotional stimuli. Across two online experiments, participants completed the GAMBIT task in one session (Experiment 1, N = 300) or repeated over three sessions (Experiment 2, N = 65). The task included No-Go trials to train preemptive inhibition, stop-signal trials for reactive inhibition, and stop-signal anticipation trials to train proactive inhibition. Affective images of differing valence were presented as background stimuli to evaluate their impact on inhibitory performance. In Experiment 1, participants showed higher accuracy on No-Go versus reference Go trials ({beta}=1.45, SE=0.09, p<.001), confirming successful manipulation of preemptive inhibition. Reaction times were slower during anticipation trials across two different conditions ({beta}=0.16, SE=0.04, p<.001; {beta} = 0.07, SE = 0.04, p = 0.047), consistent with proactive slowing when anticipating a potential stop signal. Additionally, positive affective images ({beta} = 0.10, SE= 0.009, p < 0.001) further slowed RTs, indicating emotional interference with proactive control. In Experiment 2, the pattern of higher No-Go accuracy was replicated ({beta} = 0.91, SE = 0.11, p < .001) and accuracy generally improved over sessions ({beta} = 0.38, SE = 0.06, p < .001). In anticipation trials, RTs become shorter across sessions (session 2: {beta} = -0.25, SE = 0.06, p < .001; session 3: {beta} = -0.45, SE = 0.06, p < .001), reflecting practice-related gains, and SSRTs decreased over time (F(2,56) = 6.26, p = .004), consistent with enhanced reactive inhibition. Proactive inhibition was modulated by affective images, with both negative ({beta} = 0.04, SE = 0.02, p = .039) and positive ({beta} = 0.16, SE = 0.02, p < .001) affective images associated with slower RTs. Participants also reported reductions in self-assessed temper control by the last session (W = 25.5, p = .007, q = .037, d = -0.51) and usability ratings were high (all means [&ge;] 3.87/5). Together, these findings show that this paradigm recruits multiple forms of inhibitory control and yields training-related improvements in both performance and affective outcomes. This provides preliminary validation of a scalable, fully online inhibitory control training tool targeting multiple dissociable inhibitory processes within affective contexts. The approach holds promise as an accessible transdiagnostic intervention to support symptom improvement across psychiatric disorders, with future work needed to evaluate clinical efficacy in patient populations.

Background At present, there are no approved pharmacological treatments for people at clinical high risk for psychosis (CHR-P). We sought to assess the acceptability of cannabidiol (CBD): a promising candidate treatment for this population. Methods CHR-P individuals completed a survey which assessed their views on the acceptability of CBD, its expected effectiveness and side effects, and on formulation preferences. Results The sample comprised 55 CHR-P individuals (24.3 years and 69% female). Most (91%) were familiar with CBD, and had previously used cannabis (64%), and around half (42%) had tried over-the-counter CBD. 75% were willing to take CBD as an intervention for mental health problems. Most participants anticipated fewer side effects with CBD than with existing medications, and preferred tablet or capsule formulations over liquids. Discussion CBD is perceived as a highly acceptable treatment among CHR-P individuals.

Actigraphy is a popular behavioral sleep assessment tool in research and clinical practice. Hierarchical hand-scoring approaches remain the standard for actigraphy rest interval estimation, but can be impractical for large cohort studies and suffer from reproducibility problems. We developed a semi-automated pipeline (actiSleep) to set rest intervals consistent with best-practice hand-scoring algorithms incorporating event marker, diary, light, and activity data. To evaluate actiSleep performance, we used data from an observational study of 51 adolescents (14-19yr), with and without family history of bipolar disorder. Participants completed 2 weeks of wrist actigraphy and daily sleep diary. We first hand-scored records using a standardized hierarchical algorithm incorporating event marker, diary, light, and activity data. We then compared the hand-scored rest intervals to those from actiSleep and two automated activity-based algorithms (Activity-Merged, Activity-Only). Activity-Only used activity-based sleep estimation and Activity-Merged joined closely adjacent rest intervals. For rest onset, rest offset, and rest duration, all algorithms had strong mean agreement with hand-scoring: actiSleep estimates were within 1-3 minutes, Activity-Merged within 2-4 minutes, and Activity-Only within 7-14 minutes. However, actiSleep had notably better (narrower) margins of agreement with hand-scoring, as evidenced by Bland-Altman plots, and greater positive predictive value and true positive rates for rest detection, especially in the 60 minutes surrounding the onset and offset of the rest interval. The actiSleep algorithm successfully estimates actigraphy rest intervals comparable to hand-scoring while avoiding pitfalls of activity-only algorithms. actiSleep has potential to replace hand-scoring for research in adolescents but requires further testing and validation in other samples.

Objective: Posttraumatic stress disorder (PTSD) after a traumatic birth is a serious but overlooked maternal morbidity, affecting ~20% of women following medically complicated deliveries. PTSD can undermine maternal caregiving. Rapid screening tools suited to busy obstetric settings are lacking. We developed and evaluated a brief screener, derived from the 20-item PTSD Checklist for DSM-5 (PCL-5), to identify PTSD related to childbirth. Study Design: We enrolled 107 women with traumatic childbirth. Participants completed the PCL-5 and the gold-standard clinician diagnostic interview for PTSD (CAPS-5); depression was measured with the Edinburgh Postnatal Depression Scale (EPDS). Bootstrap resampling with LASSO regression identified PCL-5 items most associated with PTSD. Firth logistic regression models estimated diagnostic accuracy. Sensitivity, specificity, area under the ROC curve (AUC), and Youden's J statistic determined performance and optimal cut-off. Results: A six-item version of the PCL-5 (PCL-5 R6), statistically derived from the full scale, showed excellent discrimination for PTSD compared with clinician evaluation (AUC = 0.95; 95% CI, 0.89-1.00). A cut-off score of 7 yielded high sensitivity (0.96) and good specificity (0.83), with an overall diagnostic efficiency of 0.86, detecting most PTSD cases while minimizing false positives. The PCL-5 R6 correlated moderately with the EPDS (rho = 0.53), showing that a depression screen alone cannot reliably detect PTSD. Conclusions: A short, 6-item PCL-5 provides a valid, efficient tool for detecting childbirth PTSD. Its brevity and accuracy make it practical for integration into routine postpartum care, enabling timely mental health screening.

Importance: Lung cancer mortality in the United States has fallen substantially in recent decades, yet the relative influence of behavioral, environmental, socioeconomic, and therapeutic factors and their sex specific contributions remains unclear. Understanding these drivers is essential to sustain progress and reduce persistent disparities. Objective: To quantify how behavioral, environmental, socioeconomic, and therapeutic determinants collectively shaped US lung cancer mortality from 1994 to 2020, assess sex specific differences, and forecast mortality trajectories through 2030 using an integrated machine learning framework. Design, Setting, and Participants: Ecological time series study using publicly available national data from 1994 to 2020. Sex stratified analyses were conducted integrating lung cancer mortality, smoking prevalence, fine particulate matter PM2.5 exposure, Human Development Index HDI, per capita healthcare expenditure, healthcare inflation, insurance coverage, income inequality, and annual drug approvals. Exposures: Behavioral smoking, environmental PM2.5, socioeconomic HDI health expenditure inflation, uninsurance inequality, and therapeutic drug approval indicators. Main Outcomes and Measures: Age-standardized lung cancer mortality per 100000 population. Temporal changes were modeled using Joinpoint regression. Concurrent associations were assessed using multivariable and elastic net regression, and forecasts were estimated with AutoRegressive Integrated Moving Average models with exogenous variables ARIMAX. Results: From 1994 to 2020, mortality declined by 59 percent in men, from 52.9 to 21.7 per 100000, and by 40 percent in women, from 26.7 to 15.9 per 100000, with faster declines after 2015. Smoking and PM2.5 decreased by more than 45 percent but remained strongly correlated with mortality. In elastic net models, PM2.5 was the strongest predictor for men, while smoking was the strongest predictor for women. Per capita expenditure and HDI ranked higher for men, while uninsurance and income inequality were strong predictors for women. Mortality declines occurred during periods of major approvals of lung cancer drugs. Forecasts suggest continued but slower declines through 2030, with projected rates of 20.2 and 14.9 deaths per 100000 in men and women, respectively. Conclusions and Relevance: Sex specific declines in lung cancer mortality reflect different dominant correlates, with air pollution more important in men and smoking more important in women, while socioeconomic conditions and therapeutic advances also influence trends. Continued tobacco control, improved air quality, and equitable access to screening and modern treatment are essential to sustain further reductions in mortality. Keywords: Lung Neoplasms, Sex Factors, Air Pollution, Smoking, Socioeconomic Factors, Machine Learning

Accurate classification of BRCA1 and BRCA2 variants is essential for cancer risk assessment and therapy selection, yet over one-third remain variants of uncertain significance (VUS). Here, using 120,660 real-world cancer genomic profiles with BRCA1 or BRCA2 variants from a >800,000-sample cohort, we develop machine learning models that predict pathogenicity using clinical and tumor-derived features, including a pan-cancer homologous recombination deficiency signature, co-mutated genes, zygosity, and cancer type. Trained on classified variants from ClinVar, our models achieved near-perfect performance, with validation ROC-AUC of 1.000 for BRCA1 and 0.989 for BRCA2 variants with [&ge;]5 observations, translating to strong benign or pathogenic evidence for VCEP classification. Applying these models to 1,073 BRCA1 and 1,639 BRCA2 VUS, we strengthened or enabled classification of 39.48% BRCA1 and 50.52% BRCA2 assessable variants. This approach transforms underutilized tumor profiling data into evidence that can be directly integrated into variant classification, providing a scalable framework for other tumor profiling datasets and cancer genes associated with defined tumor genomic features.

A critical challenge in endocrine neurosurgery is intraoperative discrimination between normal pituitary tissue and pituitary neuroendocrine tumors (PitNETs). Suggesting the universal persistence of near-infrared autofluorescence (NIRAF) in endocrine organs and inspired by routine clinical use of NIRAF for parathyroid gland identification, we discovered that pituitary NIRAF can be employed for label-free transsphenoidal surgery guidance. Ex vivo confocal spectral imaging of 33 specimens identified secretory granules as the dominant long-wavelength fluorescence source and showed that normal pituitary had higher granule content than PitNETs. For the first time, we made use of the pituitary NIRAF during surgery and assessed its performance for pituitary/adenoma separation in vivo for 27 surgeries and showed near-perfect separability between pituitary and non-pituitary measurement sites with ROC-AUC of 0.98. The obtained results clearly demonstrate that the suggested method, based on the solid microscopic background, has the potential for clinical translation and paves the way for enhanced gland preservation during resection.

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.

Despite the relevance of spatial mapping in analyzing the health situation and understanding the risk factors and determinants of leptospirosis, peripheral urban communities often remain invisible on maps, which tend to use data and methods that do not express community contribution nor promote local participation. Furthermore, in the implementation of sanitation interventions, the same happens: there is limited user participation, and a lack of identification of intervention needs based on the perception of community residents, failing the interventions. We conducted a cross-sectional study through collaborative mapping from February to October 2022 with 213 residents and self-declared heads-of-household in two peripheral urban communities. We analyzed the perception of sanitation needs indicated by residents and their relationship with the risk of leptospirosis in these communities. Based on community perception, sewage (NS: 87.1%; JSI/ME: 84.9%) and urban cleaning and solid waste management (NS: 25.9%; JSI/ME: 32.6%) were the sanitation needs. In NS, most participants indicated that the necessary interventions for sewage improvement were actions of sewer cleaning and sealing (26.5%), sewer cleaning and piping (23.5%), and implementation/installation/construction of a sanitary sewage network (41.4%). In JSI/ME, interventions included sewage sealing (48.7%) and piping (25.6%), in addition to actions to maintain sewage cleaning (93.3%). The removal of solid waste (trash) in the square (NS: 22.2%) and on the streets (JSI/ME: 69.2%), as well as community awareness (JSI/ME: 15.4%), were indicated as interventions to meet the needs of urban cleaning and solid waste management. Respondents agreed on where interventions should occur, which congregated around the local river. We found a negative correlation between the predicted leptospirosis seropositivity and perceived intervention needs in both study areas. The prevention of diseases such as leptospirosis in peripheral urban communities requires integrated basic sanitation interventions, encompassing different components and aligned with the local needs perceived by residents.

Purpose: Tumor genomic testing (TGT) is standard-of-care for most patients with advanced/metastatic cancer. Despite established guidelines, patient education prior to TGT is frequently omitted. The purpose of this study was to evaluate the impact and durability of a concise 3-4 minute video for patient education prior to TGT in community versus academic sites and across cancer types. Patients and Methods: Patients undergoing standard-of-care TGT were enrolled at a tertiary academic institution in three cohorts: Cohort 1-breast cancer; Cohort 2-lung cancer; Cohort 3-other cancers. Cohort 4 consisted of patients with any cancer type similarly undergoing SOC TGT at one of three community cancer centers. Participants completed survey measures prior to video viewing (T1), immediately post-viewing (T2), and after return of TGT results (T3). Outcome measures included: 1) 10-question objective genomic knowledge/understanding (GKU); 2) 10-question video message-specific knowledge (VMSK); 3) 11-question Trust in Physician/Provider (TIPP); 4) perceptions regarding TGT. Results: A total of 203 participants completed all survey timepoints. Higher baseline GKU and VMSK scores were significantly associated with higher income and greater years of education. For the primary objective, there was a significant and sustained improvement in VMSK from T1:T2:T3 (Poverall p<0.0001), with no significant change in GKU (p=0.41) or TIPP (p=0.73). This trend was consistent within each cohort (all p[&le;]0.0001). Results for four VMSK questions significantly improved, including impact on treatment decisions, incidental germline findings, and insurance coverage of testing. Conclusions: A concise, 3-4 minute, broadly applicable educational video administered prior to TGT significantly and sustainably improved video message-specific knowledge in diverse cancer types and in academic and community settings. This resource is publicly available at http://www.tumor-testing.com, with a goal to efficiently educate and empower patients regarding TGT while addressing guidelines within the flow of clinical practice.

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.

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.

Abstract Background: Urinary tract infections (UTIs) are common health issue during pregnancy, often lead to adverse maternal and neonatal outcomes if left untreated, low knowledge contribute to high UTI rates, particularly in resource-limited settings like Jordan. To assess the knowledge levels about UTIs among pregnant women in Jordan and its association with socio-demographic characteristics. Methods: A descriptive cross-sectional study was conducted among 500 pregnant women attending antenatal clinics in four major governmental hospitals across Jordan. Data were collected using a validated questionnaire based on the Theory of Planned Behavior (TPB) comprising 25 questions, including 5 socio-demographic questions and 20 knowledge questions, scores were categorized as "adequate" or "inadequate" based on the median score. Results: Among participants, 51.4% had inadequate knowledge, while 48.6% demonstrated adequate knowledge. Higher knowledge levels were significantly associated with younger age (21-30 years), urban residence, higher education (university and postgraduate), and employment status. Conclusion: The findings highlight a knowledge gap among pregnant women regarding UTIs. Integrating targeted health education and addressing socio-demographic disparities into antenatal care, especially for women with low education and rural residence, may improve maternal outcomes. Keywords: Urinary tract infection, Knowledge, Pregnancy, Antenatal care, Jordan, Maternal health.

Background: Nursing interns are at high risk of psychological distress due to academic and clinical stressors. While poor sleep quality is linked to anxiety and depression, the buffering role of social support remains underexplored in this population. Aims: To explore the role of social support in regulating the relationship between sleep and mental health among nursing interns. Methods: A total of 396 nursing interns completed self-administered questionnaires including the Pittsburgh Sleep Quality Index (PSQI), Social Support Rate Scale (SSRS), Generalized Anxiety Disorder-7 (GAD-7), and Patient Health Questionnaire-9 (PHQ-9). Hierarchical regression and simple slope analyses were used to test moderation effects. Results: Poor sleep quality was significantly associated with higher anxiety ({beta}=0.449, P<0.001) and depression ({beta}=0.535, P<0.001). Social support significantly moderated these relationships. Under low social support, the effects of sleep quality on anxiety ({beta} = 0.602) and depression ({beta} = 0.779) were stronger than under high support (anxiety: {beta} = 0.396; depression: {beta} = 0.515). Conclusions: Social support buffers the adverse psychological effects of poor sleep among nursing interns. Interventions should integrate sleep hygiene education with strategies to enhance social support.

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.

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 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.

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.