The Lancet Regional Health - Western Pacific
○ Elsevier BV
Preprints posted in the last 7 days, ranked by how well they match The Lancet Regional Health - Western Pacific's content profile, based on 14 papers previously published here. The average preprint has a 0.04% match score for this journal, so anything above that is already an above-average fit.
Liu, Z.; Ren, C.; Liu, J.; Kawasaki, Y.; Bishai, D. M.
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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.
Wagle, U.; Sirur, F. M.; Lath, V.; Lingappa, D. J.; R, R.; Kulkarni, N. U.; Kamath, A.
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Background The Hump-nosed pit viper is a recognized but neglected medically significant species causing morbidity and mortality, with non-availability of a specific antivenom. There are many gaps in our understanding of its envenomation, including burden, clinical syndrome, complications and management. Methodology The study is a retrospective sub analysis of the Prospective VENOMS registry and hospital records of Hump Nosed Pit Viper envenomation from a single tertiary care center in coastal Karnataka from May 2018 to March 2024. Epidemiology, syndrome, complications and treatment strategies have been described. A linear mixed model analysis was conducted to study the effect of different therapeutic interventions in combating venom induced consumptive coagulopathy (VICC) Principal Findings Of 46 cases, 24 patients had VICC. The most common complications were AKI (21.7%), TMA (10.9%) and stroke (4.4%). Anaphylaxis to ASV (23.9%) was the most common therapeutic complication. Therapeutic interventions included ASV, administration of blood products and therapeutic plasma exchange along with supportive care. The linear mixed model revealed that administration of blood products (p=<0.001) had the strongest influence on the INR value, however, often resulting in a transient decline in INR value. ASV (p=0.052) caused only marginally significant change in INR. The role of TPE could not be statistically inferred, however, individual cases with severe VICC improved without complications, therefore it required further study but can be considered in critical cases. Conclusions/Significance This study describes the syndrome of hump-nosed pit viper envenomation, while highlighting the urgent need for a species-specific antivenom, recommends treatment strategies that can be used in the interim. Additionally, geo-spatial mapping draws attention to hotspots and the hypothesis that HNPV in coastal Karnataka have regionally distinct toxicity trends.
Legendre, E.; Dutrey-Kaiser, A.; Attalah, Y.; Boyer, G.; Nauleau, S.; Gaudart, J.; Kelly, D.; Caserio-Schönemann, C.; Malfait, P.; Chaud, P.; Ramalli, L.; Gastaldi, C.; Franke, F.; Rebaudet, S.
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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.
Yu, J.
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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.
Cortes-Flores, H.; Torrandell-Haro, G.; Brinton, R. D.
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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.
Sedda, L.; Ochomo, E.; Tadesse, F.; Khaireh, B. A.; Demissew, A.; Demisse, M.; Getachew, D.; Guelleh, S.; Ibrahim, M. M.; Abongo, B.; Moshi, V.; Muchoki, M.; Polo, B.; Kipingu, A. M.; Mlacha, Y. P.; Sangoro, O.; Adeleke, M.; Adeogun, A. O.; Ayodele, B.; Okumu, F. O.; Pang, X.; Ferguson, H. M.; Kiware, S.
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The spread of Anopheles stephensi into the Horn of Africa represents one of the main challenges for malaria control, given the species ecological plasticity and resistance to multiple insecticides. In response to the World Health Organizations 2022 vector alert, an adaptive, model-based spatial surveillance framework was developed and evaluated to improve detection, mapping accuracy, and operational responsiveness during invasion. Adaptive surveillance utilises initial observations to guide subsequent surveillance, linking the surveillance design to the underlying geographical characteristics of Anopheles stephensi distribution through observed data. This dynamic approach targets areas of high uncertainty and/or abundance, making the design responsive rather than predetermined. Focusing on Djibouti and selected regions of Ethiopia and Kenya, the adaptive surveillance was designed on previous in-country Anopheles stephensi surveillance data integrated with assembled open-source environmental, epidemiological, and demographic covariates. Key driver factors of the average monthly Anopheles stephensi catches varied geographically, although seasonality was universally important. Adaptive site allocation was optimised using a multicriteria target function which combines the trapping probability and uncertainty from previous surveys, with a simulation based on peaks-over-threshold (generalized Pareto) modelling of exceedances and Bayes factor-guided prioritisation. The selected adaptive surveillance design is the one that minimise the uncertainty in Anopheles stephensi trapping probability in hotspot areas. Optimal adaptive designs required between 50 to 59 sites per country, with uncertainty reductions in the probability of trapping projected up to 36% in Djibouti and more than 60% in Ethiopia and Kenya, with more than 60% site implementation halving uncertainty in Djibouti and Kenya and reducing it by up to 75% in Ethiopia. The proposed adaptive surveillance framework operationalises WHO guidance, accelerates hotspot identification, and inform targeted ecological studies and control interventions. It is extensible to other urban vectors (e.g., Aedes aegypti), enabling integrated, cross-border surveillance essential to contain Anopheles stephensi during ongoing invasion.
Liffert, H.; Parajuli, S.; Shoaib, M.; Meier, B.; Chavez, L.; Perkins, J. C.
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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.
Clay, J. M.; Lawrence, K. W.; Johal, P. K.; Sherk, A.; Stockwell, T.; Naimi, T.
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Objective: Minimum unit pricing (MUP) aims to reduce use of cheap, high strength alcoholic beverages that drive harm, yet concerns remain about inequitable effects for structurally vulnerable groups. As part of the Costs, Harms, Expenditures and Alcohol Prices (CHEAP) study, we linked individual-level, product-specific alcohol consumption data from a customized survey with provincial retail price data to estimate prices per standard drink (PPSD) and examine their association with alcohol-related outcomes across sociodemographic groups. Method: A cross-sectional survey of past-week drinkers in British Columbia, Canada, was linked to provincial product-level alcohol sales data. The population weighted sample included 1,217 adults aged [≥] 19 years (716 men; mean age 49.34, SD 16.98). Participants reported product-specific consumption, which was matched to retail prices to calculate individual-level PPSD. Survey weighted quasibinomial models then examined associations between PPSD and three outcomes: (1) causing harm to self or others in the past year, (2) scoring [≥] 8 on the Alcohol Use Disorder Identification Test, and (3) consuming [≥] 15 standard drinks per week. Analyses were stratified by income, education, subjective social status, and race/ethnicity. Results: Lower price per standard drink was associated with higher odds of harm (OR 3.05, 95% CI 1.25-7.40) and scoring [≥] 8 on the AUDIT (OR 2.34, 95% CI 1.37-3.99). Associations were stronger among structurally disadvantaged groups, including low-income respondents and Indigenous participants. Conclusions: Lower alcohol affordability is linked to risky alcohol use, with the strongest effects among structurally disadvantaged groups. MUP would reduce this risk and promote health equity.
Gallagher, D.; Spyreli, E.; Calder-MacPhee, N.; Crossley, K.; Feuillatre, C.; Ivory, A.; Karatas, B.; Kelly, C. B.; Lind, M.; Osei-Asemani, E.; Potrick, R.; Stanton, H.; Bridges, S.; Coulman, E.; Free, C.; Hoddinott, P.; Anderson, A. S.; Cardwell, C. R.; Dombrowski, S. U.; Heaney, S.; Kee, F.; McDowell, C.; McIntosh, E.; Murphy, L.; Woodside, J. V.; McKinley, M. C.
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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.
Ledder, G.
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With significant population fractions in many societies who refuse vaccines, it is important to reconsider how vaccination is incorporated into compartmental epidemiology models. It is still most common to apply the vaccination rate to the entire class of susceptibles, rather than to use the more realistic assumption that the vaccination rate function should depend only on the population of susceptibles who are willing and able to receive a vaccination. This study uses a simple generic disease model to address two questions: (1) How much error is introduced in key model outcomes by neglecting vaccine unwillingness?, and (2) Can the error be reduced by incorporating vaccine unwillingness into the vaccination rate constant rather than the rate diagram? The answers depend greatly on the time scale of interest. For the endemic time scale, where longterm behavior is studied with equilibrium point analysis, the error in neglecting unwillingess is large and cannot be improved upon by decreasing the vaccination rate constant. For the epidemic time scale, where the first big epidemic wave is studied with numerical simulations, the error can still be significant, particularly for diseases that are relatively less infectious and vaccination programs that are relatively slow.
Justen, L. J.; Rushford, C.; Hershey, O. S.; Floyd-O'Sullivan, R.; Grimm, S. L.; Bradshaw, W. J.; Bhasin, H.; Rice, D. P.; Stansifer, K.; Faraguna, J. D.; McLaren, M. R.; Zulli, A.; Tovar-Mendez, A.; Copen, E.; Shelton, K. K.; Amirali, A.; Kannoly, S.; Pesantez, S.; Stanciu, A.; Quiroga, I. C.; Silvera, L.; Greenwood, N.; Bongiovi, B.; Walkins, A.; Love, R.; Lening, S.; Patterson, K.; Johnston, T.; Hernandez, S.; Benitez, A.; McCarley, B. J.; Engelage, S.; Pillay, S.; Calender, C.; Herring, B.; Robinson, C.; Monett Wastewater Treatment Plant, ; Columbia Missouri Wastewater Treatment Plant, ;
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Wastewater monitoring enables non-invasive, population-scale tracking of community infections independent of healthcare-seeking behavior and clinical diagnosis. Metagenomic sequencing extends this capability by enabling broad, pathogen-agnostic detection, genomic characterization, and identification of novel or unexpected threats. Here, we present data from CASPER (the Coalition for Agnostic Sequencing of Pathogens from Environmental Reservoirs), a U.S.-based wastewater metagenomic sequencing network designed for deep, untargeted pathogen monitoring at national scale. This release includes 1,206 samples collected between December 2023 and December 2025 from 27 sites across nine states, covering 13 million people. Deep sequencing (~1 billion read pairs per sample) generated 1.2 trillion read pairs (347 terabases), enabling detection of even rare taxa, with CASPER representing 66% of all untargeted wastewater sequencing data currently available on the NCBI Sequence Read Archive. Virus abundance trends correlate with nationwide wastewater PCR and clinical data for SARS-CoV-2, influenza A, and respiratory syncytial virus, while the pathogen-agnostic approach captures emerging threats, including avian influenza H5N1 during initial dairy cattle outbreaks, West Nile virus, and measles, among hundreds of viral taxa. As the largest publicly available untargeted wastewater sequencing dataset to date, CASPER provides a shared and growing resource for pathogen surveillance and microbial ecology.
Solotchi, M.; Jing, H.; Gebauer, E.; Novick, S. J.; Pascal, B. D.; Tung, W.; Hanpude, P.; Zhang, Y.; Alba, C.; Saracino, A.; Laghetti, P.; Shaw, E. R.; Rosen, L. B.; Holland, S. M.; Lisco, A.; Dalgard, C. L.; Marcotrigiano, J.; Griffin, P. R.; Su, H. C.; Patel, S. S.
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RIG-I is a cytosolic immune receptor that provides the first line of defense by detecting viral RNA and triggering antiviral responses. Its physiological role in humans remains unclear, as no patients with complete RIG-I deficiency have yet been reported. We identified a critically ill COVID-19 patient with severe RIG-I deficiency caused by heterozygous RIG-I G731R, a novel dominant loss-of-function variant. The G731R mutation in helicase motif VI disrupts the arginine finger, impairing the ATPase activity of RIG-I, but not its RNA-binding ability. However, viral RNA binding fails to expose the signaling domains, thereby impairing the IFN-{beta} response of G731R. Instead, G731R competes with wild-type RIG-I, exerting a dominant negative effect. The loss-of-function is caused by bulky-charged substitutions at G731, as alanine or leucine substitution results in an unexpected gain-of-function phenotype. These findings highlight the importance of uncompromised RIG-I function for human antiviral immunity and the pleiotropic effects of single mutations.
Malik, M. Z.; Mian, N. u.; Memon, Z.; Mirza, M. W.; Rana, U. F.; Alvi, M. A.; Ahmed, W.; Ummad, A.; Ali, A.; Naveed, U.; Malik, K. S.; Chaudhary, M. S.; Waheed, M.; Sattar, A.
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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.
Apostolov, A.; Pathare, A. D. S.; Lavogina, D.; Zhao, C.; Kask, K.; Blanco Rodriguez, L.; Ruiz-Duran, S.; Risal, S.; Rooda, I.; Damdimopoulou, P.; Saare, M.; Peters, M.; Koistinen, H.; Acharya, G.; Zamani Esteki, M.; Lanner, F.; Sola Leyva, A.; Salumets, A.
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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.
Swinnen, M.; Gys, L.; Thalwitzer, K.; Deporte, A.; Van Gorp, C.; Vermeer, E.; Salami, F.; Weckhuysen, S.; Wolf, S. I.; Syrbe, S.; Schoonjans, A.-S.; Hallemans, A.; Stamberger, H.
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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.
Syed, M. A.; Alnuaimi, A. S.; El Kaissi, D. B.; Syed, M. A.
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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.
Alawdat, s.; Hassan, Z. M.
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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.
Gandhi, N. R.; Fernandes Gyorfy, M.; Paradkar, M.; Jennet Mofokeng, N.; Figueiredo, M. C.; Prakash, S.; Prudhula Devalraju, K.; Hui, Q.; Willis, F.; Mave, V.; Andrade, B. B.; Moloantoa, T.; Kumar Neela, V. S.; Campbell, A.; Liu, C.; Young, A.; Cordeiro-Santos, M.; Gaikwad, S.; Karyakarte, R. P.; Rolla, V. C.; Kritski, A. L.; Collins, J. M.; Shah, N. S.; Brust, J. C. M.; Lakshmi Valluri, V.; Sarkar, S.; Sterling, T. R.; Martinson, N. A.; Gupta, A.; Sun, Y. V.
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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.
Johnson, L. R.; Bond, C. W.; Noonan, B. C.
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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.
Moser, J. D.; Bond, C. W.; Noonan, B. C.
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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.