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Abstract Background The effects of war on biodiversity, habitats, ecosystem services, and water, seafood, and fishing resources are complex and long-lasting, yet their ongoing environmental analyses are limited. The Russia–Ukraine War (2022–present) comprises a unique ecological situation to examine biodiversity effects on the distinctive cold-temperate northern Black Sea ecosystem, which has an intriguing biogeographic history and high endemism resulting from geographic isolation and differentiation. Results We summarize negative and positive effects from the War on the aquatic (marine, estuarine, and freshwater) biota and their habitats, focusing on investigations by the Institute of Marine Biology, National Academy of Sciences of Ukraine. Negative effects include toxins and habitat damage from oil spills, shelling, mining, explosions, flooding, and fires; along with disregard of Protected Areas. Positive effects are reduced anthropogenic loads from less shipping, fishing, trawling, recreation, hydraulic engineering, construction, and tourism. The Kakhovka Dam’s destruction on June 6, 2023 was the greatest ecological catastrophe to date, causing extensive downstream flooding with freshwaters and pollutants that destroyed many populations and habitats. We discern that many effects have been temporary, with habitats and species replenishing, and some reverting to their historical biota characteristic of lower salinity regimes. However, significant habitat destruction, disturbances, and pollutant damages remain. Since many of the native species evolved in conditions favoring broad salinity, temperature, and oxygen tolerances, the northern Black Sea ecosystem appears pre-adapted for ecological recovery and persistence, which may equate to ecological resilience during and after the War. Conclusions The native biota exhibits long-term adaptiveness to marked salinity and temperature fluctuations, alongside a background of invasive species. An evolutionary and recent history of broad environmental tolerances by a large proportion of Black Sea species may enhance their ability to withstand marked environmental changes, including habitat destruction, as during the Kakhovka Dam's breakage and other stressors that continue during the Russia–Ukraine War. The Black Sea community’s overall ecological resilience is likely to facilitate persistence and adaptation to the War’s effects and the accelerating impacts of climate change, increased global transportation, and invasive species—meriting worldwide conservation agency focus and cooperation.

Abstract Background Large language models are increasingly evaluated for use in healthcare. However, concerns about their impact on disparities persist. This study reviews current research on demographic biases in large language models to identify prevalent bias types, assess measurement methods, and evaluate mitigation strategies. Methods We conducted a systematic review, searching publications from January 2018 to July 2024 across five databases. We included peer-reviewed studies evaluating demographic biases in large language models, focusing on gender, race, ethnicity, age, and other factors. Study quality was assessed using the Joanna Briggs Institute Critical Appraisal Tools. Results Our review included 24 studies. Of these, 22 (91.7%) identified biases. Gender bias was the most prevalent, reported in 15 of 16 studies (93.7%). Racial or ethnic biases were observed in 10 of 11 studies (90.9%). Only two studies found minimal or no bias in certain contexts. Mitigation strategies mainly included prompt engineering, with varying effectiveness. However, these findings are tempered by a potential publication bias, as studies with negative results are less frequently published. Conclusion Biases are observed in large language models across various medical domains. While bias detection is improving, effective mitigation strategies are still developing. As LLMs increasingly influence critical decisions, addressing these biases and their resultant disparities is essential for ensuring fair artificial intelligence systems. Future research should focus on a wider range of demographic factors, intersectional analyses, and non-Western cultural contexts. Graphic Abstract

Abstract The global outbreak of clade 2.3.4.4b H5N1 highly pathogenic influenza A virus (HP H5N1) has had an unprecedented impact on wild birds including raptors, but long-term population impacts have not been addressed. To determine if raptors survive infections with HP H5N1, raptors from the upper Midwest United States were serologically tested for antibodies to influenza A virus (IAV), H5 and N1. Raptors were sampled at The Raptor Center’s (University of Minnesota) wildlife rehabilitation hospital and at Hawk Ridge Bird Observatory. Samples were tested for IAV antibodies using a commercially available blocking ELISA, with positive samples tested for antibodies to H5 and N1. Antibodies to IAV were detected in 86 out of 316 individuals representing 7 species. Antibodies to H5 and N1 were detected in 60 individuals representing 6 species. Bald eagles had the highest seroprevalence with 67/97 (69.1%) seropositive for IAV and 52 of these 67 (77.6%) testing positive for antibodies to both H5 and N1. Prevalence of antibodies to IAV observed in this study was higher than reported from raptors sampled in this same region in 2012. The high prevalence of antibodies to H5 and N1 indicates a higher survival rate post-HP H5N1 infection in raptors than previously believed.

Abstract Background Sleep, physical activity, and nutrition (SPAN) are critical behaviours for health, although they have traditionally been studied separately. We examined the combined associations of SPAN and the minimum between-individual variations associated with meaningfully lower all-cause mortality risk. Methods This prospective cohort analysis included 59,078 participants from the UK Biobank (median age: 64.0 years; 45.4% male) who wore trackers for 7 days and self-reported dietary data. Wearable-measured sleep (hours/day) and moderate to vigorous physical activity (MVPA; mins/day) were calculated using a machine learning based schema. A 10-item diet quality score (DQS) assessed the intake of vegetables, fruits, fish, dairy, whole grains, vegetable oils, refined grains, processed and unprocessed meats, and sugary beverages (0–100 for all components with higher values indicating higher quality). Cox proportional hazards models were used to estimate hazard ratios (HR) for all-cause mortality risk across 27 separate joint tertile combinations of SPAN behaviours with the lowest tertile for all three as the referent group. For more granular clinical interpretations, we examined combined incremental dose–response changes of the SPAN behaviours using the 5th percentile of each behaviour as the referent point. Results Over the 8.1-year median follow-up time, 2,458 mortality events occurred. Compared to the referent group of combined SPAN exposure (lowest tertiles for all three), the optimal SPAN combination involving moderate sleep duration (7.2–8.0 h/day), high MVPA (42–103 min/day), and a DQS between 57.5 and 72.5 was associated with an HR of 0.36 (95% CI: 0.26–0.50). Relative to the 5th percentile of sleep (5.5 h/day), physical activity (7.3 min/day), and nutrition (36.9 DQS), a theoretical minimum combined increase of 15 min/day of sleep, 1.6 min/day MVPA, and 5 DQS points (corresponding to e.g., extra 1/2 serving of vegetables per day or 1 less serving of processed meat per week) was associated with 10% lower all-cause mortality risk (0.90; 0.88–0.93). Combined increases of 75 min/day of sleep, 12.5 min/day MVPA, and 25 DQS points were associated with 50% lower all-cause mortality risk (0.50; 0.44–0.58). Conclusions This study highlights the potential health value of subtle combined SPAN modification in relation to mortality risk and expands opportunities for more holistic recommendations.

Abstract We assess three words commonly used to represent the environmental dimensions of antimicrobial resistance (AMR) – ‘hotspot’, ‘reservoir’ and ‘pristine’ – through two questions: how are these terms used in published research; and how do these terms shape research being conducted? We advocate for the community to reflect on and improve its use of language, and suggest four potentially more productive and precise terms for AMR hazard: presence; transmission; evolution and connectivity.

Abstract Background There is limited high-quality research examining conservative treatments for back-related leg pain (BRLP). This feasibility study was done in preparation for a full-scale trial comparing a whole-person supported self-management intervention to medical care for chronic BRLP. Methods Participants were randomized to 12 weeks of individualized supported self-management delivered by physical therapists and chiropractors or medical care consisting of guideline-based pharmacologic care. Supported self-management was based on a behavioral model that used a whole person approach to enhance participants capabilities, opportunities, and motivations to engage in self-care. It combined BRLP education with psychosocial strategies (e.g., relaxed breathing, progressive muscle relaxation, guided imagery, communication skills) and physical modalities such as exercise and spinal manipulation therapy. Providers were trained to address participants’ individualized needs and use behavior change and motivational communication techniques to develop a therapeutic alliance to facilitate self-management. Feasibility was assessed using pre-specified targets for recruitment and enrollment, intervention delivery, and data collection over the six-month study period. In addition, areas for potential refinement and optimization of processes and protocols for the full-scale trial were assessed. Results We met or exceeded nearly all feasibility targets. Forty-two participants were enrolled over a six-month period in 2022 and very few individuals declined participation due to preferences for one treatment. All but one participant received treatment and 95% of participants attended the minimum number of visits (self-management = 6, medical care = 2). At 12 weeks, 95% of participants in the self-management group reported engaging in self-management practices learned in the program and 77% of medical care participants reported taking medications as prescribed. Satisfaction with the self-management intervention was high with 85% of participants reporting satisfaction with the program overall. Self-management intervention providers delivered all required activities at 72% of visits. Providers also noted some challenges navigating the shared decision-making process and deciding what self-management tools to prioritize. Over the six-month study period, completion rates were 91% for monthly surveys and 86% for weekly surveys. Conclusion We were able to demonstrate that a full-scale randomized trial comparing a whole-person supported self-management intervention to medical care for chronic BRLP is feasible and identified important areas for optimization.

Abstract Structural stigma towards gender minority (GM; people whose current gender does not align with sex assigned at birth) people is an important contributor to minority stress (i.e., stress experienced due to one’s marginalized GM identity), although existing variables are unclear in their inclusion of social norms, or societal stigma, as a key component of the construct. We examined potential variables representing structural stigma, including variables that are inclusive of societal stigma, to identify those that most strongly relate to minority stress outcomes. We tested variables identified in the literature as measures of structural stigma inclusive of societal stigma (LGBT + Business Climate Index, state voting behaviors, and Google Trends search data), the most commonly used structural stigma variable (State Policy Environment Tally), and proxy variables (region, population density) for comparison. The relationships between structural stigma and minority stress model outcomes were tested in a sample of GM participants from The Population Research in Identity and Disparities for Equality (PRIDE) Study (N = 2,094) 2019 Annual Questionnaire using a structural equation model (SEM). Lower structural stigma (i.e., higher LGBT Business Climate Index) was associated with lower experienced stigma (β= -0.260, p

Abstract Background Tuberous Sclerosis Complex (TSC) is a rare genetic condition caused by mutation to TSC1 or TSC2 genes, with a population prevalence of 1/7000 births. TSC manifests behaviorally with features of autism, epilepsy, and intellectual disability. Resting state electroencephalography (EEG) offers a window into neural oscillatory activity and may serve as an intermediate biomarker between gene expression and behavioral manifestations. Such a biomarker could be useful in clinical trials as an endpoint or predictor of treatment response. However, seizures and antiepileptic medications also affect resting neural oscillatory activity and could undermine the utility of resting state EEG features as biomarkers in neurodevelopmental disorders such as TSC. Methods This paper compares resting state EEG features in a cross-sectional cohort of young children with TSC (n = 49, ages 12–37 months) to 49 age- and sex-matched typically developing controls. Within children with TSC, associations were examined between resting state EEG features, seizure severity composite score, and use of GABA agonists. Results Compared to matched typically developing children, children with TSC showed significantly greater beta power in permutation cluster analyses. Children with TSC also showed significantly greater aperiodic offset (reflecting nonoscillatory neuronal firing) after power spectra were parameterized using SpecParam into aperiodic and periodic components. Within children with TSC, both greater seizure severity and use of GABAergic antiepileptic medication were significantly and independently associated with increased periodic peak beta power. Conclusions The elevated peak beta power observed in children with TSC compared to matched typically developing controls may be driven by both seizures and GABA agonist use. It is recommended to collect seizure and medication data alongside EEG data for clinical trials. These results highlight the challenge of using resting state EEG features as biomarkers in trials with neurodevelopmental disabilities when epilepsy and anti-epileptic medication are common.

Abstract Background Sotrovimab is a neutralising monoclonal antibody (nMAB) currently available to treat extremely clinically vulnerable COVID-19 patients in England. Trials have shown it to have mild to moderate side effects, however, evidence regarding its safety in real-world settings remains insufficient. Methods Descriptive and multivariable logistic regression analyses were conducted to evaluate uptake, and a self-controlled case series analysis performed to measure the risk of hospital admission (hospitalisation) associated with 49 pre-specified suspected adverse outcomes in the period 2–28 days post-Sotrovimab treatment among eligible patients treated between December 11, 2021 and May 24, 2022. Results Here we show that among treated and untreated eligible individuals, the mean ages (54.6 years, SD: 16.1 vs 54.1, SD: 18.3) and sex distribution (women: 60.9% vs 58.1%; men: 38.9% vs 41.1%) are similar. There are marked variations in uptake between ethnic groups, which is higher amongst individuals categorised ethnically as Indian (15.0%; 95%CI 13.8, 16.3), Other Asian (13.7%; 95%CI 11.9, 15.8), white (13.4%; 95%CI 13.3, 13.6), and Bangladeshi (11.4%; 95%CI 8.8, 14.6); and lower amongst Black Caribbean individuals (6.4%; 95%CI 5.4, 7.5) and Black Africans (4.7%; 95%CI 4.1, 5.4). We find no increased risk of any of the suspected adverse outcomes in the period 2–28 days post-treatment. Conclusions We find no safety signals of concern for possible adverse outcomes in the period 2-28 days post treatment with Sotrovimab. However, there is evidence of unequal uptake of Sotrovimab treatment across ethnic groups.

Few sources have reported empirical social contact data from resource-poor settings. To address this shortfall, we recruited 1,363 participants from rural and urban areas of Mozambique during the COVID-19 pandemic, determining age, sex, and relation to the contact for each person. Participants reported a mean of 8.3 (95% CI 8.0–8.6) contacts per person. The mean contact rates were higher in the rural site compared with the urban site (9.8 vs 6.8; p

Abstract Combined immune checkpoint blockade (ICB) and chemoradiation (CRT) is approved in patients with locally advanced cervical cancer (LACC) but optimal sequencing of CRT and ICB is unknown. NRG-GY017 (NCT03738228) was a randomized phase I trial of atezolizumab (anti-PD-L1) neoadjuvant and concurrent with CRT (Arm A) vs. concurrent with CRT (Arm B) in patients with high-risk node-positive LACC. The primary endpoint was the fraction of expanded tumor-associated T-cell receptor (TCR) clones in blood at day 21 as a surrogate measure of anti-tumor immune response. Secondary objectives were safety and feasibility, 2-year disease-free survival (DFS), and predictive value of PD-L1 expression. Forty patients were randomized, 36 received treatment, and 25 were evaluable for the primary endpoint. After cycle 1, there was peripheral expansion of higher proportion of tumor-associated TCR clones in Arm A than in Arm B (p = 0.0025) that remained higher at day 21, meeting the pre-specified endpoint on two-sample T-test (p = 0.052), but not on sensitivity analysis by Wilcoxon test (p = 0.13). At the median follow up of 25.8 months, 2-year DFS was 76% in Arm A and 56% in Arm B (p = 0.28). There were no new safety signals. In conclusion, neoadjuvant ICB prior to CRT was safe and was associated with immunologically and clinically favorable outcomes, warranting larger confirmatory studies.

Abstract Background HIV prevalence among female sex workers (FSW) is significantly higher than among women in the general population. Studies have shown that FSW engage in unprotected sex which provides higher compensation when they face emergency situations. We co-created a savings intervention – Jitegemee (rely on yourself) – with FSW to encourage them to save part of their earnings to withdraw in emergency situations in order to reduce risk. Methods We undertook a five-phase intervention development process between February 2021 and July 2023: 1) qualitative interviews with FSW to identify essential intervention features; 2) pilot trial to assess intervention feasibility; 3) literature review of studies on economic empowerment of FSW; 4) scoring of key components of Phases 1–3 on a scale of 1–5 (1 = definitely exclude, 5 = definitely include), for inclusion in the intervention package; 5) workshops with FSW and other key stakeholders to co-design the intervention. Results In phase 1, nearly all participants (99%) found the intervention acceptable to them and 95% believed it would be acceptable to other FSW. Participants suggested inclusion of financial literacy (75%), savings groups (38%) and goal-setting (24%). In the feasibility assessment, 41% saved, of whom 46% withdrew some savings. Condom use was higher among FSW who withdrew their savings compared to those who did not (χ 2 7.52; p = 0.006). In Phase 3, we identified 14 intervention components. In phase 4, all suggested intervention components scored 4.5 on average. In phase 5, we held 3 workshops with FSW to co-design the intervention, which included instructions for how to save and make withdrawals, financial literacy training, and formation of savings groups. Conclusions A savings intervention for and by FSW was highly acceptable and feasible. Involving end-users in the design process is likely to result in greater economic security among FSW and lower engagement in higher risk transactional sex.

Summary: Background: Children from racial and ethnic minority groups are at greater risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but it is unclear whether they have increased risk for post-acute sequelae of SARS-CoV-2 (PASC). Our objectives were to assess whether the risk of respiratory and neurologic PASC differs by race/ethnicity and social drivers of health. Methods: We conducted a retrospective cohort study of individuals

Abstract Background Type 2 diabetes (T2D) has become a worldwide pandemic. While ceramides may serve as intermediary between obesity-related lipotoxicity and T2D, the relationship with simple glycosphingolipids remains uncertain. The aim of this study was to characterize the associations between blood glycosphingolipid and ceramide species with T2D and to identify a circulating sphingolipid profile that could serve as novel biomarker for T2D risk. Methods Cross-sectional relationship between sphingolipid levels, insulin resistance, and T2D prevalence were evaluated in 2,072 American adults from MIDUS cohort. Prospectively, the association between sphingolipid species and the incidence of T2D was analyzed using a case-cohort design nested within the PREDIMED trial (250 cases and a random sample of 692 participants, with 3.8 years of median follow-up). Circulating levels of sphingolipid species in both populations were measured using LC/MS. Hazard ratios were estimated with weighted Cox regression models using Barlow weights. Results In American adults, only CER18:0 and CER22:0 were linked to insulin resistance and a higher prevalence of T2D. Conversely, three lactosylceramides (LCER 14:0, 16:0, and 24:1) showed a strong inverse relationship with both insulin resistance and T2D. These findings led to development of two sphingolipid scores. In the prospective analysis, these scores consistently predicted a reduced risk of T2D incidence in PREDIMED (HR: 0.64, 95% CI 0.44 to 0.94 and 0.58, 0.40 to 0.85 respectively) between extreme quartiles, with 5-year absolute risk differences of 9.6% (95% CI: 0.3–20.5%) and 11.4% (1.0–21.6%). They were validated in the same trial with samples obtained after 1 year of follow-up. Conclusions Our findings support the potential usefulness of circulating sphingolipid profiles as novel biomarkers for T2D risk. Moreover, this study opens the door for future research on the predictive value and possible protective roles of lactosylceramides in T2D. Graphical abstract

Abstract Background The introduction of poly(ADP-ribose) polymerase (PARP) inhibitors represented a paradigm shift in the treatment of ovarian cancer. Genomic data from patients with high-grade ovarian cancer in six phase II/III trials involving the PARP inhibitor olaparib were analyzed to better understand patterns and potential causes of genomic instability. Patients and methods Homologous recombination deficiency (HRD) was assessed in 2147 tumor samples from SOLO1, PAOLA-1, Study 19, SOLO2, OPINION, and LIGHT using next-generation sequencing technology. Genomic instability scores (GIS) were assessed in BRCA1 and/or BRCA2 (BRCA)-mutated (BRCAm), non-BRCA homologous recombination repair-mutated (non-BRCA HRRm), and non-HRRm tumors. Results BRCAm was identified in 1021/2147 (47.6%) tumors. BRCAm tumors had significantly higher GIS than non-BRCAm tumors (P

Abstract A non-invasive, accessible and effective biomarker is critical to the diagnosis, monitoring and treatment of age-related cognitive decline. Recent work has suggested a strong association between auditory brainstem responses (ABR) and cognitive function in aging macaques. Here we show in 118 human participants (66 females; age range=18-92 years; hearing loss = -5 to 70 dB HL) that cognition is associated with both age and hearing level, but this triad relationship is mainly driven by the age factor. After adjusting for age, cognition is still significantly associated with both the ABR wave V amplitude (B, 0.110, 95% CI, 0.018– 0.202; p = 0.020) and latency (B, -0.101, 95% CI, -0.186– -0.016; p = 0.021). Importantly, this age-adjusted ABR-cognition association is primarily driven by older individuals and language-dependent cognitive functions. We also perform the area under the curve (AUC) of the receiver-operating-characteristic analysis and find that the ABR wave V amplitude is best for detecting good cognitive performers (AUC = 0.96) whereas the wave V latency is best for detecting poor ones (AUC = 0.86). The present result not only confirms the previous animal work in humans but also shows the clinical potential of using auditory brainstem responses to improve diagnosis and treatment of age-related cognitive decline.

Background: The ketogenic diet (KD), characterized by high-fat content, virtually no carbohydrates, and adequate protein intake, induces a metabolic state resembling fasting, as the absence of carbohydrates forces the body to rely on the energetic supply from hepatically produced ketone bodies using free fatty acids as substrate. While the KD is clinically used in pharmacologically refractory epilepsy and specific genetic conditions such as GLUT1 deficiency, recent research suggests that, due to its “fasting mimicking” properties, the KD may also beneficially affect obesity and obesity-associated metabolic diseases. Results: Here, we present a narrative review discussing completed and ongoing nutritional studies in human volunteers specifically addressing the potential of the ketogenic diet as an anti-obesity approach and, from a larger perspective, as an intervention to ameliorate the metabolic state in conditions such as type 1 and 2 diabetes and polycystic ovary syndrome (PCOS). Published studies as well as ongoing clinical trials will be discussed. Efficacy and safety considerations will be discussed, as well as the potential physiological mechanisms mediating the effects of the KD in humans in the context of the (i) energy balance model (EBM) and (ii) carbohydrate–insulin model (CIM) of body weight control. Conclusion: Ketogenic diets may be beneficial to attenuate obesity and improve obesity-related metabolic disease, and here, we try, based on current evidence, to define the boundaries of the KD’s nutritional and clinical usefulness.

Abstract Introduction Quality midwifery education is central to improving midwifery service delivery and maternal and newborn health outcomes. In many settings, midwifery educators insufficiently prepared for their teaching role and deficient curriculum compared to international standards affect the quality of healthcare provided by the midwifery graduates. This study assessed the effectiveness of an EmONC enhanced midwifery curriculum delivered by trained and mentored midwifery educators on the quality of education and student performance in Kenya. Methods A cluster randomised controlled trial in 20 midwifery colleges (12 intervention, 8 control colleges). Educators in both arms received training in teaching/EmONC skills to deliver the updated national midwifery curriculum. The intervention arm received additional 3-monthly post-training mentoring for 12 months. Educators’ knowledge and confidence in EmONC/teaching skills was assessed before and after training and at 3, 6, 9 and 12 months. Teaching skills observations at baseline and endline in both study arms were also assessed. Knowledge, self-rated confidence and three OSCE in EmONC practical skills among final year midwifery students were assessed. Linear mixed effects models were used to evaluate the effect of intervention on educators and students. Results Seventy four educators and 146 students participated. Training significantly improved educators’ mean knowledge (61.3%-73.3%) and confidence to teach EmONC (3.1–4.2 out of 5). Observed teaching skills mean scores of educators in the intervention arm were significantly higher compared to those of controls at endline (89.4%-vs-72.2%, mean difference 17.2 [95%CI, 3.2–29.8]). Mean scores for students in the intervention arm were significantly higher than those in controls for knowledge (59.6%-vs-51.3%, mean difference 8.3 [95%CI, 1.6–15.0]) and the three skills assessed (means; mean difference (95%CI): shoulder dystocia (64.5%-vs-42.7%; 21.8 (10.8–33.9); newborn resuscitation (43.9% vs 26.1%; 17.8 (2.0–33.9); and maternal shock resuscitation (56.5%-vs-39.2%; 17.3 (8.0–26.0) and combined average skills scores (55.0%-vs-36.0; 19.0 (8.7–29.5). Conclusion Training and supportive mentoring improved the quality of educators’ teaching pedagogy and EmONC skills and enhanced students’ learning. Overall performance in EmONC knowledge and skills was significantly higher for students who were taught by trained and mentored educators compared to those who received training alone. Thus, a local mentoring system is effective to enhance learning and effectiveness of an EmONC-updated midwifery curriculum.

Abstract Background The relationship between COVID-19 infection and a possible increased likelihood of older adults developing new-onset dementia (NOD) remains elusive. Methods A thorough search was performed across several databases including MEDLINE/PubMed, PsycINFO, Scopus, medRxiv, and PQDT Global for studies published in English from January 2020 to December 2023. Only original investigations exploring the link between COVID-19 infection and NOD were selected for inclusion. We assessed the risk of developing NOD, using Risk Ratio (RR) for measurement. Control groups were categorized as: (i) a non-COVID cohort with other respiratory infections [control group (C1)]; and (ii) a non-COVID cohort with otherwise unspecified health status [control group (C2)]. Follow-up periods were divided into intervals of 3, 6, 12, and 24 months post-COVID. Results 11 studies (involving 939,824 post-COVID-19 survivors and 6,765,117 controls) were included in the review. Across a median observation period of 12 months post-COVID, the overall incidence of NOD was about 1.82% in the COVID-infected group, compared to 0.35% in the non-COVID-infected group. The overall pooled meta-analysis showed a significantly increased NOD risk among COVID-19 older adult survivors compared to non-COVID-19 controls (RR = 1.58, 95% CI 1.21–2.08). Similar increased NOD risks were observed in subgroup analyses restricted to an observational period of 12 months (RR = 1.56, 95% CI 1.21–2.01), as well as in five studies that employed propensity score matching to sufficiently and effectively control for multiple confounding covariates (RR = 1.46, 95% CI 1.10–1.94). COVID-19 group and C1 group shared a comparably increased risk of developing NOD (overall RR = 1.13, 95% CI 0.92–1.38). Discussion Under normal circumstances, we believe that COVID-19 infection is likely to be a risk factor for developing NOD in older adults over time. While the increased NOD risk due to COVID-19 infection appears to be similar to that associated with other respiratory infections, it warrants and necessitates investigation with longer observations.

Abstract Aims The efficacy of beta‐blockers in cardiac amyloidosis (CA) is unclear, and concerns persist that neurohormonal blockade could worsen symptoms of heart failure. We aimed to assess whether beta‐blocker therapy is associated with improved survival in patients with CA. Methods and results We conducted a systematic review and meta‐analysis to examine the impact of beta‐blocker therapy on mortality in patients with CA. A search of MEDLINE and EMBASE was performed in August 2023. Data were extracted from observational studies and synthesized with pooling and random effects meta‐analysis. Thirteen studies including 4215 patients with CA were incorporated in this review (3688 transthyretin amyloid cardiomyopathy (ATTR‐CM), 502 light chain amyloid cardiomyopathy (AL‐CM), 25 not specified; age 74.8 ± 5.5 years, 76% male). Over half of the cohort (52%) received beta‐blockers and the rate of beta‐blocker withdrawal was 28%. All‐cause mortality was 33% (range: 13–51%) after a median follow‐up ranging from 13 to 36 months. There was an inverse association between the pooled risk of mortality and the use of beta‐blocker therapy at any time point (RR 0.48, 95% CI 0.29–0.80, I2 = 83%, P = 0.005, seven studies). There was no association between mortality and beta‐blocker use (RR 0.65, 95% CI 0.29–1.47, I2 = 88%, P = 0.30) in the three studies that only included patients with ATTR‐CM. The three studies that included patients with both ATTR‐CM and AL demonstrated an association of beta‐blocker use with reduced mortality (OR 0.43, 95% CI 0.29–0.63, I2 = 4%, P

Communicating risks and mitigation benefits associated with natural hazards such as wind to the general public is challenging given the location-dependency of parameters and the complexity of the problem. Web tools play a crucial role in educating residents, decision-makers, and stakeholders regarding potential wind hazard losses to, for example, residential buildings.However, a notable gap exists on the practical incorporation of mitigation actions within these tools. This gap hampers the collective awareness and understanding among stakeholders, communities, and citizens regarding the tangible advantages of mitigation strategies in reducing wind-related risks. Furthermore, there exists a need to elucidate the functionality and objectives of these tools in a more accessible manner. This study aims to present and outline the wind risk and mitigation calculator tool (WRMCT) within the Hazardaware platform, which is an address-based risk assessment tool. This tool, developed for 196 counties in the Gulf of Mexico coastal area, facilitates users' education of potential risks and benefits associated with mitigation strategies. WRMCT enables users to access location-specific wind risk and interactively suggests potential mitigation actions along with economic savings to support informed decisions and residential risk reduction. WRMCT intends to enhance users’ ability to make informed decisions, take proactive measures in mitigating wind hazards, and contribute to the development of resilient, residential communities.

In the rapidly evolving landscape of medical imaging, the integration of artificial intelligence (AI) with clinical expertise offers unprecedented opportunities to enhance diagnostic precision and accuracy. Yet, the ''black box'' nature of AI models often limits their integration into clinical practice, where transparency and interpretability are important. This paper presents a novel system leveraging the Large Multimodal Model (LMM) to bridge the gap between AI predictions and the cognitive processes of radiologists. This system consists of two core modules, Temporally Grounded Intention Detection (TGID) and Region Extraction (RE). The TGID module predicts the radiologist's intentions by analyzing eye gaze fixation heatmap videos and corresponding radiology reports. Additionally, the RE module extracts regions of interest that align with these intentions, mirroring the radiologist’s diagnostic focus. This approach introduces a new task, radiologist intention detection, and is the first application of Dense Video Captioning (DVC) in the medical domain. By making AI systems more interpretable and aligned with radiologist’s cognitive processes, this proposed system aims to enhance trust, improve diagnostic accuracy, and support medical education. Additionally, it holds the potential for automated error correction, guiding junior radiologists, and fostering more effective training and feedback mechanisms. This work sets a precedent for future research in AI-driven healthcare, offering a pathway towards transparent, trustworthy, and human-centered AI systems. We evaluated this model using NLG(Natural Language Generation), time-related, and vision-based metrics, demonstrating superior performance in generating temporally grounded intentions on REFLACX and EGD-CXR datasets. This model also demonstrated strong predictive accuracy in overlap scores for medical abnormalities and effective region extraction with high IoU(Intersection over Union), especially in complex cases like cardiomegaly and edema. These results highlight the system's potential to enhance diagnostic accuracy and support continuous learning in radiology.

Introduction: A large proportion of the existing voluminous disaster mental health research literature represents the quantitative study of psychopathology, especially posttraumatic stress disorder. Subjective disaster experience is relatively unexplored. Qualitative narratives of surviving a disaster may provide insight into individual experiences of it and efforts to derive meaning from it. Methods: From an initial random sample of 182 survivors of the Oklahoma City bombing, narrative descriptions of this experience were collected 7 years after the bomb blast from 116 of the original sample, for the purpose of examining persistent as well as newly evolving content through qualitative analysis. The narrative content was analyzed for the evolution of thematic content in narrative data also collected at 6 months post-disaster and 1 year later. Results: The thematic content of the bombing experience was structured in a chronological fashion from the bomb blast (sensory, cognitive, and emotional), its immediate aftermath (e.g., escaping danger), and later experiences, (e.g., leaving the bomb site and receiving hospital treatment). During the time between interviews, the focus and general content of the narratives changed minimally, despite considerable compression of detail. Conclusions: The consistency of the material in these narratives over 7 years may reflect the persistence and salience of disaster memories, with the potential for its continuation for the rest of their lives.

Abstract Coral reef ecosystems are under threat from climate change. Thus, active interventions to spur coral conservation/restoration are critical to support reef survival, greatly informed by a molecular understanding of resilience. The genus Acropora is a species-rich and globally prevalent reef builder that has experienced dramatic declines in the Caribbean. Here we generated a draft genome of the common coral Acropora hemprichii from the central Red Sea, one of the warmest water bodies in the world. We assembled the genome using 10x Chromium sequencing with subsequent scaffolding using a reference genome and Illumina short-read sequencing contigs. The A. hemprichii genome has an assembly size of 495.6 Mb confirmed using physical size estimation, of which 247.8 Mb (50%) are repeats. The scaffold N50 is 1.38 Mb with 99.6% of BUSCO genes identified (93.7% complete, 5.9% fragmented), providing a set of 26,865 protein-coding genes. The Red Sea A. hemprichii reference genome provides a valuable resource for studies aiming to decode the genomic architecture of resilience, e.g. through comparative analyses with other Acropora genomes.

Abstract Background The Canadian Chiropractic Association (CCA) initiated a quality improvement project to develop best practices aimed at enhancing the patient experience. Objectives (1) Identify and prioritise the key moments in the new patient experience that could be improved by providing chiropractors with focused support and resources; (2) explore views, barriers, and enablers to implementing these best practices; and (3) develop recommendations to facilitate the adoption of these practices. Methods We conducted a qualitative needs assessment using a human-centred design approach, focused on understanding the needs and experiences of end-users to create tailored solutions. The Theoretical Domains Framework (TDF) was employed to explore chiropractors’ knowledge use and behaviour change, and TDF domains were mapped to Behaviour Change Techniques (BCTs) to develop targeted strategies for addressing identified barriers and enablers. Thirteen chiropractors from across Canada participated in semi-structured interviews and related activities. Results The key moments where participants felt they needed the most support were “treatment”, “report of findings”, “informed consent”, “physical examination”, and “before the appointment”. All participants agreed with the best practices seed statements. Key barriers included gaps in knowledge, communication skills, and resource availability, particularly in rural areas. Enablers included collaboration with other health professionals, mentorship, and access to practice tools. Recommendations include enhanced training in communication and treatment planning, increased access to resources in rural areas, and fostering collaborative relationships among health professionals. Conclusion Understanding the barriers and enablers to implementing best practices can inform targeted strategies to improve patient-centred care in chiropractic practice across Canada.

Abstract Background Exposures to endocrine disrupting chemicals (EDCs) have been linked to chronic diseases including breast cancer, metabolic syndrome, diabetes, and infertility. Exposure during pregnancy may have a lifelong impact on the fetus. Services are needed to allow individuals to learn about their personal EDC exposures and how to reduce them. Million Marker (MM) aims to crowdsource and scale the biomonitoring of environmental chemicals and provide actionable results to empower individuals to proactively assess, track, and reduce their EDC exposures. In previous research, we developed and tested the first mobile EDC intervention service (mail-in urine testing and exposure report-back) for its efficacy in increasing EH literacy (EHL), willingness to reduce exposures (i.e., readiness to change, RtC), and system usability. After intervention, we found increased EHL, increased RtC in women (but not men), and decreased EDC exposure. However, some participants did not increase their RtC and had difficulty carrying out the intervention on their own. The reasons for these less optimal results were the difficulty in the EHL subject matter—participants still felt ill-prepared to apply their knowledge to making healthier lifestyle changes. Therefore, in this study, we will address these perceived limitations. Methods We will test a self-directed online interactive curriculum with live counseling sessions and individualized support modeled after the highly effective Diabetes Prevention Program (DPP). Recruiting from the Healthy Nevada Project (HNP), one of the largest population health cohorts in the world, we test the effectiveness of our EDC-specific online intervention curriculum via EHL and RtC surveys and determine changes in EDC exposure before and after intervention in a randomized controlled trial. We will also test for common clinical biomarkers via a commercially available at-home test (Siphox). We will recruit and randomize 300 women and 300 men of reproductive age (total n=600) from HNP. Our target population is men and women of reproductive age (18–44 years old). Discussion At the conclusion of this project, we will be well-positioned to scale our services to clinics and the general public, with the eventual aims of FDA approval, insurance coverage, and incorporation into routine clinical care.

Abstract Background Variants in the CTSB gene encoding the lysosomal hydrolase cathepsin B (catB) are associated with increased risk of Parkinson’s disease (PD). However, neither the specific CTSB variants driving these associations nor the functional pathways that link catB to PD pathogenesis have been characterized. CatB activity contributes to lysosomal protein degradation and regulates signaling processes involved in autophagy and lysosome biogenesis. Previous in vitro studies have found that catB can cleave monomeric and fibrillar alpha-synuclein, a key protein involved in the pathogenesis of PD that accumulates in the brains of PD patients. However, truncated synuclein isoforms generated by catB cleavage have an increased propensity to aggregate. Thus, catB activity could potentially contribute to lysosomal degradation and clearance of pathogenic alpha synuclein from the cell, but also has the potential of enhancing synuclein pathology by generating aggregation-prone truncations. Therefore, the mechanisms linking catB to PD pathophysiology remain to be clarified. Methods Here, we conducted genetic analyses of the association between common and rare CTSB variants and risk of PD. We then used genetic and pharmacological approaches to manipulate catB expression and function in cell lines, induced pluripotent stem cell-derived dopaminergic neurons and midbrain organoids and assessed lysosomal activity and the handling of aggregated synuclein fibrils. Results We find that catB inhibition impairs autophagy, reduces glucocerebrosidase (encoded by GBA1) activity, and leads to an accumulation of lysosomal content. In cell lines, reduction of CTSB gene expression impairs the degradation of pre-formed alpha-synuclein fibrils, whereas CTSB gene activation enhances fibril clearance. In midbrain organoids and dopaminergic neurons treated with alpha-synuclein fibrils, catB inhibition potentiates the formation of inclusions which stain positively for phosphorylated alpha-synuclein. Conclusions These results indicate that the reduction of catB function negatively impacts lysosomal pathways associated with PD pathogenesis, while conversely catB activation could promote the clearance of pathogenic alpha-synuclein.

Abstract People with a history of injecting drug use are a priority for eliminating blood-borne viruses and sexually transmissible infections. Identifying them for disease surveillance in electronic medical records (EMRs) is challenged by sparsity of predictors. This study introduced a novel approach to phenotype people who have injected drugs using structured EMR data and interactive human-in-the-loop methods. We iteratively trained random forest classifiers removing important features and adding new positive labels each time. The initial model achieved 92.7% precision and 93.5% recall. Models maintained >90% precision and recall after nine iterations, revealing combinations of less obvious features influencing predictions. Applied to approximately 1.7 million patients, the final model identified 128,704 (7.7%) patients as potentially having injected drugs, beyond the 50,510 (2.9%) with known indicators of injecting drug use. This process produced explainable models that revealed otherwise hidden combinations of predictors, offering an adaptive approach to addressing the inherent challenge of inconsistently missing data in EMRs.

Abstract Background Children and adolescents’ physical inactivity is a global problem. Financial incentives are increasingly utilised to support children’s participation in sport, with programs introduced in multiple jurisdictions globally, however few programs have comprehensive evaluations. This study used a Delphi methodology to develop evaluation recommendations for an existing population-wide financial incentive program based in South Australia. Methods A three-round Delphi study was conducted from October 2022 to April 2023. A diverse range of stakeholders including end-users, government representatives, academics/researchers, and Non-Government Organisation representatives participated in the Delphi panel. Round 1 focussed on the perceived importance of various evaluation components, including reach, process, and effectiveness. Round 2 focussed on identifying evaluation approaches and tools, while Round 3 determined methodological priorities and timeframes. A consensus level of ≥ 70% was set a priori (rating 6 or 7 on 7-point scale). Round 3 results were used to formulate evaluation recommendations. Results Sixty-seven stakeholders agreed to participate, with an average response rate of 76% (87%; 73% and 67% for each round, respectively). All evaluation components gained consensus in Round 1. In Round 2, consensus was gained on 14 evaluation measures, including measuring the cost of sport, awareness of the program amongst eligible families, and reasons for non-participation, with evaluation methods generated for each measure. Round 3 results determined participants’ preferred methods of evaluation and informed the development of evaluation recommendations. Recommended evaluation methods included mixed method approaches for provider and user process evaluations and measuring program awareness using an epidemiological survey. Conclusion This Delphi study sought the views and opinions from diverse stakeholders to create evaluation recommendations for a population-wide sports voucher program. Results suggested that a comprehensive evaluation strategy is needed to understand the reach, effectiveness, and impact of the program. Additionally, there was a consensus on reallocating program funds for this evaluation.

Abstract Objective The objective of this study was to establish a zone of clinical equipoise for the Proximal FEmur Resection or Internal Fixation fOR Metastases (PERFORM) randomized controlled trial, which will compare resection and endoprosthetic reconstruction to internal fixation for skeletal metastases of the proximal femur. Methods A survey was developed, piloted, and distributed to self-declared interested stakeholders in the PERFORM trial. The survey targeted orthopedic oncologists and was designed to assess patient and bone lesion characteristics that drive surgical decision-making in the treatment of skeletal metastases in the proximal femur. An Ethics Waiver was obtained at the lead academic institution and data was collected in the REDCap survey database. Results Responses were complete from 76 surgeons across North America, South America, Europe, Asia, and Africa. Response rate from self-declared interested stakeholders was 70%, with additional responses collected from a broader international audience. Responses indicate that a study population for which either resection and endoprosthetic reconstruction or internal fixation are acceptable options include (1) life expectancy at least 6 months, (2) bone loss of no more than 75% and no less than 25%, and (3) minimal to moderate risk for perioperative complications. Ninety-three percent of respondents indicated that they would be interested in participating in the PERFORM trial. Conclusion A preliminary zone of equipoise for the PERFORM trial includes patients with 25–75% bone loss, low to moderate risk of operative complications, and life expectancy of at least 6 months. Further stakeholder discussions have finalized the PERFORM trial protocol prior to study initiation.

Abstract Background Preeclampsia is the second leading cause of maternal death in Uganda. WHO recommends using magnesium sulphate (MgSO4) to prevent and treat preeclampsia with severe features (PEC) and eclampsia. MgSO4 is used to prevent eclampsia and treat women who experience an eclamptic convulsion to avoid severe maternal/infant illnesses and death. We set out to assess MgSO4 administration patterns in women with PEC or eclampsia and the immediate newborn outcomes of neonates. Methods This was an analytical observational cohort study at Kawempe National Referral Hospital in Uganda. Two hundred ten pregnant mothers with PEC or eclampsia were recruited in the study after receiving the loading dose of MgSO4 and then followed through labour and delivery to observe MgSO4 administration patterns and immediate newborn outcomes using Apgar and Thompson scores. SPSS version 23 was used to analyse data, and both bivariate and multivariate logistic regressions were used to determine factors associated with the low Apgar score at five minutes. Results Overall, majority of the patients received more than one dose with 33.3% received a sixth dose of MgSO4. The majority, 84.8%, of the mothers delivered live babies, 31.0% babies had complications, and were admitted to the neonatal intensive care unit (NICU). NICU admissions were mostly due to respiratory distress21.4%, preterm delivery21.0%, and 5.5% died within seven days. Majority 93.3% of the newborns had an Apgar score of seven and above at five minutes, of the newborns who were Thompson scored, 70.4% scored between 1 to 10 which is mild HIE. Initiation of MgSO4 treatment within one hour from prescription (AOR = 0.49, CI: 0.01–1.94), 4-hourly timing of the first maintenance dose (AOR = 0.22, CI: 0.06–0.79) and having complete doses of MgSO4 treatment (AOR = 0.89, CI: 0.03–3.05) decreased the likelihood of having low Apgar scores at five minutes. Conclusions Timely administration of the first maintenance dose of MgSO4 decreases the likelihood of low Apgar score at 5 min and NICU admission in newborns, and most NICU admissions were due to respiratory distress and preterm delivery.

Aims: Lower limb fractures are common in low- and middle-income countries (LMICs) and represent a significant burden to the existing orthopaedic surgical infrastructure. In high income country (HIC) settings, internal fixation is the standard of care due to its superior outcomes. In LMICs, external fixation is often the surgical treatment of choice due to limited supplies, cost considerations, and its perceived lower complication rate. The aim of this systematic review protocol is identifying differences in rates of infection, nonunion, and malunion of extra-articular femoral and tibial shaft fractures in LMICs treated with either internal or external fixation. Methods: This systematic review protocol describes a broad search of multiple databases to identify eligible papers. Studies must be published after 2000, include at least five patients, patients must be aged > 16 years or treated as skeletally mature, and the paper must describe a fracture of interest and at least one of our primary outcomes of interest. We did not place restrictions on language or journal. All abstracts and full texts will be screened and extracted by two independent reviewers. Risk of bias and quality of evidence will be analyzed using standardized appraisal tools. A random-effects meta-analysis followed by a subgroup analysis will be performed, given the anticipated heterogeneity among studies, if sufficient data are available. Conclusion: The lack of easily accessible LMIC outcome data, combined with international clinical guidelines that are often developed by HIC surgeons for use in HIC environments, makes the clinical decision-making process infinitely more difficult for surgeons in LMICs. This protocol will guide research on surgical management, outcomes, and complications of lower limb shaft fractures in LMICs, and can help guide policy development for better surgical intervention delivery and improve global surgical care. Cite this article: Bone Jt Open 2024;5(11):1020–1026.

Abstract The lack of a permissive cell culture system has limited high-resolution structures of parvovirus B19 (B19V) to virus-like particles (VLPs). In this study, we present the atomic resolution structure (2.2 Å) of authentic B19V purified from a patient blood sample. There are significant differences compared to non-infectious VLPs. Most strikingly, two host protease inhibitors (PIs), inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) and serpinA3, were identified in complex with the capsids in all patient samples tested. The ITIH4 binds specifically to the icosahedral fivefold axis and serpinA3 occupies the twofold axis. The protein-coated virions remain infectious, and the capsid-associated PIs retain activity; however, upon virion interaction with target cells, the PIs dissociate from the capsid prior to viral entry. Our finding of an infectious virion shielded by bound host serum proteins suggests an evolutionarily favored phenomenon to evade immune surveillance and escape host protease activity.

Anti‐HER2 therapy is indicated for erb‐b2 receptor tyrosine kinase 2 (ERBB2)‐amplified/overexpressing endometrial carcinoma (EC). Mutations constitute another mode of ERBB2 activation, but only rare ERBB2‐mutated ECs have been reported. We sought to characterize the clinicopathologic and genetic features of ERBB2‐mutated EC. From an institutional cohort of 2638 ECs subjected to clinical tumor‐normal panel sequencing, 69 (2.6%) with pathogenic ERBB2 mutation(s) were identified, of which 11 were also ERBB2‐amplified. The most frequent ERBB2 hotspot mutations were V842I (38%) and R678Q (25%). ERBB2 mutations were clonal in 87% of evaluable cases. Immunohistochemistry revealed low HER2 protein expression in most ERBB2‐mutated ECs (0/1+ in 66%, 2+ in 27%); all 3+ tumors (7.3%) were also ERBB2‐amplified. Compared to ERBB2‐wildtype ECs (with or without ERBB2 amplification), ERBB2‐mutated/non‐amplified ECs were enriched for the microsatellite instability‐high (MSI‐H) and, to a lesser extent, DNA polymerase epsilon, catalytic subunit (POLE) molecular subtypes, and associated with high tumor mutational burden and low chromosomal instability. Survival outcomes were similar between patients with ERBB2‐mutated/non‐amplified versus wildtype EC, whereas ERBB2 amplification was associated with worse prognosis on univariate, but not multivariate, analyses. In conclusion, ERBB2 mutation defines a rare subgroup of ECs that is pathogenically distinct from ERBB2‐wildtype and ERBB2‐amplified ECs.

Abstract Background Battling malaria’s morbidity and mortality rates demands innovative methods related to malaria diagnosis. Thick blood smears (TBS) are the gold standard for diagnosing malaria, but their coloration quality is dependent on supplies and adherence to standard protocols. Machine learning has been proposed to automate diagnosis, but the impact of smear coloration on parasite detection has not yet been fully explored. Methods To develop Coloration Analysis in Malaria (CAM), an image database containing 600 images was created. The database was randomly divided into training (70%), validation (15%), and test (15%) sets. Nineteen feature vectors were studied based on variances, correlation coefficients, and histograms (specific variables from histograms, full histograms, and principal components from the histograms). The Machine Learning Matlab Toolbox was used to select the best candidate feature vectors and machine learning classifiers. The candidate classifiers were then tuned for validation and tested to ultimately select the best one. Results This work introduces CAM, a machine learning system designed for automatic TBS image quality analysis. The results demonstrated that the cubic SVM classifier outperformed others in classifying coloration quality in TBS, achieving a true negative rate of 95% and a true positive rate of 97%. Conclusions An image-based approach was developed to automatically evaluate the coloration quality of TBS. This finding highlights the potential of image-based analysis to assess TBS coloration quality. CAM is intended to function as a supportive tool for analyzing the coloration quality of thick blood smears.

Abstract Introduction Polydrug use in the context of chemsex is commonplace among gay, bisexual, and other men-who-have-sex-with-men (GBMSM). This study aimed to examine the differences in experiences of physical, social, and psychological harms, as well as mental ill-health among GBMSM who use different combinations of methamphetamine and gamma-hydroxybutyric acid/gamma-butyrolactone (GHB/GBL) during chemsex. Method Adult GBMSM participants who had experience of chemsex in the past 12 months participated in a cross-sectional online survey in Taiwan and self-reported their sociodemographic background, sexual behaviours, mental health, and experiences of harm following a chemsex session. We used univariable and multivariable logistic regression to assess the different experiences of harm and mental ill-health among GBMSM who engaged in chemsex without using methamphetamine, used methamphetamine but not GHB/GBL, and who used both drugs. Results Out of 510 participants who completed all items included in the analysis, 24.1% engaged in chemsex without using methamphetamine, 36.9% used methamphetamine but not GHB/GBL, and 39.0% used both drugs. Eighty five percent of men who used both methamphetamine and GHB/GBL reported at least one kind of social harm after a chemsex session, such as missing dates or appointments, or appearing “high” at work, followed by used methamphetamine but not GHB/GBL (69.7%) and those without using methamphetamine (37.4%). After controlling for polydrug and frequency of drug use in the multivariable logistic regression, those who used methamphetamine but not GHB/GBL and those who used both drugs were more likely to report experiencing physical and psychological harms compared to those who did not use methamphetamine (p

Abstract Background The University of California’s Diabetes Prevention Program (UC DPP) Initiative was implemented systemwide to address diabetes and obesity risk on all 10 campuses. As little is known about implementing lifestyle change programs in university settings, we examined implementation partners’ (i.e., UC DPP leaders and campus leads) perceptions of factors influencing program success on UC campuses. Methods We conducted qualitative interviews with UC DPP leaders and campus leads to examine challenges and opportunities with university-based DPP delivery models. Interviews were recorded, professionally transcribed, and reviewed in detail by the research team. Transcripts were analyzed using rapid qualitative analysis (RQA). The study was approved by the UCLA Institutional Review Board. All implementation partners provided verbal informed consent. Results Twenty-six implementation partners (8 UC DPP leaders and 18 campus leads) completed interviews in 2021. Seven themes were identified as critical for implementation, including (1) marketing and recruitment (i.e., market and recruit broadly through established channels as well as target at-risk populations); (2) enrollment (i.e., offer the program during convenient times and let participants know what to expect); (3) use an adaptable, evidence-based program; (4) secure funding for the program, participants, lifestyle coaches, and space; (5) hire experienced and dedicated staff and lifestyle coaches; (6) ensure leadership support; and (7) utilize campus linkages and resources. Perceptions of challenges faced with respect to these themes are also described. Conclusions This is one of the first studies to examine the challenges and opportunities of delivering an intensive lifestyle change program across 10 university sites. Understanding factors that enhance success of university-based diabetes prevention programs can facilitate UC DPP efforts and help inform delivery strategies of health and wellness programs across other university settings more broadly.

Abstract Background Evidence suggests sexual and gender minoritized (SGM) childbearing individuals and their infants experience more adverse obstetric and perinatal outcomes compared to their cisgender, heterosexual counterparts. This study aimed to comprehensively map obstetric and perinatal physical health literature among SGM populations and their infants and identify knowledge gaps. Methods PubMed, Embase, CINAHL, and Web of Science Core Collection were systematically searched to identify published studies reporting obstetric and perinatal outcomes in SGM individuals or their infants. Study characteristics, sample characteristics, and outcome findings were systematically extracted and analyzed. Results Our search yielded 8,740 records; 55 studies (1981–2023) were included. Sexual orientation was measured by self-identification (72%), behavior (55%), and attraction (9%). Only one study captured all three dimensions. Inconsistent measures of sexual orientation and gender identity (SOGI) were common, and 68% conflated sex and gender. Most (85%) focused on sexual minorities, while 31% addressed gender minorities. Demographic measures employed varied widely and were inconsistent; 35% lacked race/ethnicity data, and 44% lacked socioeconomic data. Most studies (78%) examined outcomes among SGM individuals, primarily focusing on morbidity and pregnancy outcomes. Pregnancy termination was most frequently studied, while pregnancy and childbirth complications (e.g., gestational hypertension, postpartum hemorrhage) were rarely examined. Evidence of disparities were mixed. Infant outcomes were investigated in 60% of the studies, focusing on preterm birth and low birthweight. Disparities were noted among different sexual orientation and racial/ethnic groups. Qualitative insights highlighted how stigma and discriminatory care settings can lead to adverse pregnancy and birth outcomes. Conclusions Frequent conflation of sex and gender and a lack of standardized SOGI measures hinder the comparison and synthesis of existing evidence. Nuanced sociodemographic data should be collected to understand the implications of intersecting identities. Findings on perinatal health disparities were mixed, highlighting the need for standardized SOGI measures and comprehensive sociodemographic data. The impact of stigma and discriminatory care on adverse outcomes underscores the need for inclusive healthcare environments. Future research should address these gaps; research on SGM perinatal outcomes remains urgently lacking. Trial registration The review protocol was developed a priori in February 2023, registered on Open Science Framework ( https://doi.org/10.17605/OSF.IO/5DQV4 ) and published in BMJ Open ( https://bmjopen.bmj.com/content/13/11/e075443 ).

Abstract Background There is a need to develop accurate and reliable non-invasive methods to evaluate chronic kidney disease (CKD) status and assess disease progression. Given it is recognized that dysregulation in metabolic pathways occur from early CKD, there is a basis in utilizing metabolomic biomarkers to monitor CKD progression. Volatile Organic Compounds (VOCs), a form of metabolomic biomarker, are gaseous products of metabolic processes in organisms which are typically released with greater abundance in disease conditions when there is dysregulation in metabolism. How urinary VOCs reflect the abnormal metabolic profile of patients with CKD status is unknown. Our study aimed to explore this. Methods Individuals aged 18–75 years undergoing kidney biopsy were included. Pre-biopsy urine samples were collected. All biopsy samples had an interstitial fibrosis and tubular atrophy (IFTA) grade scored by standardized assessment. Urine supernatant was extracted from residue and sampled for stir bar sorptive extraction followed by Gas chromatography–mass spectrometry (GC-MS) analysis. Post-processing of GC-MS data separated complex mixtures of VOCs based on their volatility and polarity. Mass-to-charge ratios and fragment patterns were measured for individual VOCs identification and quantification. Linear discriminant analysis (LDA) was performed to assess the ability of urinary VOCs in discriminating between IFTA 0 (‘no or minimal IFTA’ i.e. 25% IFTA). Linear regression analysis adjusting for age, sex, estimated glomerular filtration rate, diabetes mellitus (DM) status, and albuminuria was conducted to determine significantly regulated urinary VOCs amongst the groups. Results 64 study participants (22 individuals IFTA 0, 15 individuals IFTA 1, 27 individuals IFTA ≥ 2) were included. There were 34 VOCs identified from GC-MS which were statistically associated with correct classification between the IFTA groups, and LDA demonstrated individuals with IFTA 0, IFTA 1 and IFTA ≥ 2 could be significantly separated by their urinary VOCs profile (p

Abstract Systemic sclerosis is a connective tissue disorder characterized by excessive fibrosis that primarily affects women, and can present as a multisystem pathology. Roughly 4-22% of patients with systemic sclerosis develop cancer, which drastically worsens prognosis. However, the mechanisms underlying systemic sclerosis initiation, propagation, and cancer development are poorly understood. We hypothesize that the inflammation and immune response associated with systemic sclerosis can trigger DNA damage, leading to elevated somatic mutagenesis, a hallmark of pre-cancerous tissues. To test our hypothesis, we culture clonal lineages of fibroblasts from the lung tissues of controls and systemic sclerosis patients and compare their mutation burdens and spectra. We find an overall increase in all major mutation types in systemic sclerosis samples compared to control lung samples, from small-scale events such as single base substitutions and insertions/deletions, to chromosome-level changes, including copy-number changes and structural variants. In the genomes of patients with systemic sclerosis, we find evidence of somatic hypermutation or kategis (typically only seen in cancer genomes), we identify mutation signatures closely resembling the error-prone translesion polymerase Polη activity, and observe an activation-induced deaminase-like mutation signature, which overlaps with genomic regions displaying kataegis.

Abstract Background Unfavourable changes occur in children’s health behaviours and outcomes during the summer holidays. This systematic review aimed to determine the effectiveness of summer holiday programs in mitigating these changes. Methods Six databases (MEDLINE, JBI, PsychINFO, Embase, ERIC and Scopus) were systematically searched for experimental controlled studies that investigated programs of at least 5 days’ duration conducted exclusively during the summer holiday period on school-aged children (5–18 years). Primary outcomes were moderate-vigorous physical activity and energy intake. Secondary outcomes were sedentary behavior, diet quality, adiposity, and cardiorespiratory fitness. Risk of Bias was assessed using the PEDro tool. Effect sizes were calculated using random-effects meta-analysis with narrative synthesis of effects by student or program characteristics. Results Ten studies (two randomised controlled trials, and eight non-randomised controlled trials) involving 1,446 participants were included. Summer programs had a significant moderate effect on reducing sedentary behaviour (g= -0.59, 95%CI= -1.16, -0.03) and significant small effects on improving moderate-to-vigorous physical activity (g = 0.35, 95%CI = 0.02, 0.67) and adiposity (g= -0.25, 95% CI = -0.39, -0.10). No significant change was detected for cardiorespiratory fitness (g = 0.43, 95%CI= -0.32, 1.17), energy intake (g= -0.06, 95% CI -2.33, 2.22), or diet quality (g = 0.20, 95%CI= -0.43, 0.83). Summer program effectiveness did not appear to differ by child sociodemographic or program characteristics. Concerns regarding bias and high heterogeneity impacted results. Conclusions Summer programs show potential in promoting healthier movement behaviours in children and supporting healthy body weight during the summer months. Although evidence from the included studies has limitations, these programs produced small to moderate effect sizes and present promising health intervention opportunities for children. Future research with more rigorous study designs and comprehensive reporting is needed to confirm these findings and better understand the impact of summer programs on children’s health. Prospero registration CRD42023409795.

ABSTRACT Although much has been learned about the entry mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), many details of the entry mechanisms of seasonal human coronaviruses (HCoVs) remain less well understood. In the present study, we used 293T cell lines stably expressing angiotensin converting enzyme (ACE2), aminopeptidase N (APN), or transmembrane serine protease 2 (TMPRSS2), which support high-level transduction of lentiviral pseudoviruses bearing spike proteins of seasonal HCoVs, HCoV-NL63, -229E, or -HKU1, respectively, to compare spike processing and virus entry pathways among these viruses. Our results showed that the entry of HCoV-NL63, -229E, and -HKU1 pseudoviruses into cells is sensitive to endosomal acidification inhibitors (chloroquine and NH4Cl), indicating entry via the endocytosis route. Although TMPRSS2 expression on target cell surface was required for HCoV-HKU1 spike-mediated entry and cell–cell fusion, we found that only the serine protease domain of TMPRSS2 and not the serine protease activity of TMPRSS2 was required for viral entry via endocytic route. However, the serine protease activity of TMPRSS2 and a furin processing site (RKRR) at the S1/S2 junction were essential for efficient HCoV-HKU1 spike-mediated cell–cell fusion. Additionally, we show that dibasic and monobasic arginine residues at the S1/S2 junctions of spike proteins of HCoV-NL63 and -229E are essential for virus entry, but multi-basic furin processing site at the S1/S2 junction was dispensable for HCoV-HKU1 viral entry. Our findings highlight features of the entry mechanisms of seasonal HCoVs that may support the development of novel treatment strategies.IMPORTANCEDetails of the entry mechanisms of seasonal human coronaviruses (HCoVs) remain to be fully explored. To investigate spike-mediated virus entry of HCoV-NL63, -229E, and -HKU1 CoVs, we employed 293T cells that stably express angiotensin converting enzyme (ACE2), aminopeptidase N (APN), or transmembrane serine protease 2 (TMPRSS2) to study entry mechanisms of pseudoviruses bearing spike proteins of HCoV-NL63, -229E, and -HKU1, respectively. We found that HCoV-NL63, -229E, and -HKU1 pseudoviruses entered cells via the endocytic route independently of cellular serine protease activity and therefore likely depended on endosomal cathepsin activity. Furthermore, we showed that arginine amino acids in S1/S2 junctions of HCoV-NL63 and -229E spikes were essential for entry but not essential for HCoV-HKU1 entry. Our results provide new insights into the S1/S2 junctional residues, cellular receptors, and protease requirements for seasonal HCoV pseudovirus entry into cells that may support the development of novel inhibitors.

This research aims to leverage existing data sources to provide new insights into the usage of Multi-Criteria Decision Analysis (MCDA) in the built environment without creating a new data collection process. The study is focused upon built environment vocations, spanning the disciplines of architecture, construction management, urban planning, real estate, facilities management, and the numerous engineering domains that support capital projects. The method of the study utilized Google search engine data from Google Trends and academic literature metadata from Web of Science, which was analyzed using Bibliometrix via the Biblioshiny interface. These datasets were cross-referenced with original data collected from a Qualtrics delivered industry questionnaire to develop a more comprehensive understanding of MCDA adoption within the built environment. The research presents a ranked list of MCDA methods used within built environment vocations in order of level of adoption, with the top five being PROMETHEE, House of Quality, Monte Carlo Simulations, TOPSIS, and Utility Theory. The results include Biblioshiny visualizations for MCDA methods studied within built environment academic papers and findings related to tool associations via key clusters, such as GIS and drone based data collection tool usage, in concert with MCDA methods. The paper presents evidence that MCDAs are more frequently used in environmental science, geography, management, and sustainability studies within the built environment relative to other design or construction oriented use cases. By integrating diverse data sources—academic publications, search engine trends, and industry responses—the research explores a multi-faceted perspective on the current state of MCDA usage, highlighting the gaps between academic focus, industry practices, and public interest. The research notes that MCDAs are often considered on an individual basis instead of approached broadly as a set of mathematical tools, possibly serving as a barrier to a more expansive understanding of the means and methods practitioners might employ.

BackgroundGlobally, women consume less alcohol than men, but alcohol consumption among women has declined less in recent years than among men. Drinking rates and alcohol-related harms vary substantially across population groups of women, and sexual minority women (eg, lesbian, bisexual, and queer) are at notably high risk. An emerging body of literature suggests that in addition to minority stress (eg, stigma, discrimination), drinking norms and drinking cultures likely influence sexual minority women’s drinking. Almost no research has explored these factors as possible targets of interventions. Sober curiosity is a rapidly growing wellness movement that may be particularly salient for sexual minority women. It encourages individuals to be “curious” about the reasons they choose to drink and alcohol’s effects on their life and health. ObjectiveThe aims of this research are to (1) explore the perspectives of the drinking social worlds of sexual minority women, their awareness of the sober curious movement, perceptions of their own and their peers’ drinking and desire to drink less, and perceived barriers and facilitations to changing their drinking behaviors and (2) identify key elements of an alcohol reduction intervention tailored for sexual minority women. MethodsWe conducted a comprehensive review of the literature on alcohol interventions with sexual minority women. The handful of studies we found paid scant attention to drinking cultures, normative beliefs, or other key elements of sober curiosity. To address the study aims, we are conducting 2 descriptive studies with adult (>18 years) sexual minority women using mixed methods. One includes focus group interviews (n=24-36) and a national survey (n=100-120) with sexual minority women in Scotland. The other includes in-depth interviews (n=18-20) with sexual minority women in the United States. Data from the 2 countries and 3 sources will be analyzed using qualitative and quantitative methods to identify patterns and relationships across data to validate or corroborate findings. ResultsEach of the studies received ethics approval in August 2023 and is currently open for recruitment. We anticipate completing data collection in spring 2025. The results of qualitative analyses will be summarized as themes, and results of survey data analyses will be summarized in tables. Findings will be presented to 2 panels of international experts who will assist in identifying critical elements of an alcohol reduction intervention tailored to the unique needs of sexual minority women. ConclusionsWith the assistance of the expert panels, we will use Acceptability, Practicability, Effectiveness, Affordability, Side-Effects, and Equity criteria to inform the development of a tailored intervention building on tenants of sober curiosity to assist sexual minority women in reducing harmful drinking. International Registered Report Identifier (IRRID)DERR1-10.2196/63282

Objectives: It is estimated that more than one billion people are affected by neglected tropical diseases (NTDs). Whilst there are existing treatments to reduce morbidity, a major challenge is creating robust programs that are both country-led and leverage the existing health systems. Using a systems thinking approach is a critical component for integrating NTD services, as it takes into account all aspects of what might otherwise be considered fragmented systems to create a more efficient system. Design: This article showcases three case studies where a systems lens was applied: (1) to examine the integration of morbidity management services into the existing health system in Sierra Leone, (2) to integrate lymphatic filariasis mass drug administration (MDA) in the polio campaign in Madagascar, and (3) to embed hydrocele surgeries into the services available in county health facilities in Kenya. Results: All three cases demonstrate the importance of using a systems lens to assess the current system using a participatory approach, allowing the teams to focus on leverage points to create the highest impact and by extension holistically address population needs. Conclusion: Systems thinking is valuable in examining key levers that affect NTD interventions. It offers stakeholders opportunities to develop responsive interventions that strengthen health systems.

Summary: Background: This study aimed to quantify prevalence, awareness, and control of hypertension in the Eastern Caribbean and identify sociodemographic correlates. Methods: Baseline data (2013–2018) from the Eastern Caribbean Health Outcomes Research Network Cohort Study (ECS) was used (n = 2961). The ECS is an ongoing longitudinal study of community-dwelling persons 40 years and older conducted in Barbados, Puerto Rico, Trinidad and Tobago, and U.S. Virgin Islands. Participants completed a self-administered health survey, clinical examination, and laboratory testing. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7) guidelines defined hypertension prevalence and control. Self-reported hypertension and clinical blood pressure values defined awareness. Binomial proportions, including 95% confidence intervals and logistic regression, were used for analyses. Findings: Analyses included 2932 participants with complete data. The mean age of participants was 57 (SD = 10.3) years, and 65.3% (n = 1916/2932) were women. Prevalence of hypertension was 57.9% (n = 1698/2932), among whom 36.8% (n = 591/1698) were unaware, and 56.4 percent (n = 624/1107) of aware persons lacked control. Persons who were 70 and older (82.9%, n = 325/392, 95% CI:79.2%–86.6%), had low educational attainment (63.4%, n = 642/1012, 95% CI:60.5%–66.4%), obese (67.2%, n = 753/1121, 95% CI:64.4%–69.9%), and low physical activity (63.3%, n = 766/1210, 95% CI:60.6%–66.0%) had the highest prevalences of hypertension. Awareness was highest among persons 70 and older (76.6%, n = 249/325, 95% CI:72.0%–81.2%), women (70.7%, n = 781/1104, 95% CI:68.1%–73.4%), and those with a usual source of healthcare (70.4%, n = 1042/1480, 95% CI:68.1%–72.7%). Persons with lower educational attainment had lowest control across sociodemographic groups (36.1%, n = 154/427, 95% CI:31.5%–40.6%). Multivariable results showed ages 70 and older (OR = 10.6, 95% CI:7.4–15.2) and obesity (OR = 4.0, 95% CI:3.1–5.1) were the strongest predictors of hypertension. Usual source of care (OR = 5.66, 95% CI:3.8–8.4) and ages 70 and older (OR = 4.2, 95% CI:2.7–6.5) were most strongly associated with awareness. Results for control were not statistically significant. Interpretation: Findings highlight challenges across the hypertension care cascade in the Eastern Caribbean, particularly with control. These findings have implications for public health and healthcare system solutions to improve screening and blood pressure control. Funding: National Heart, Lung, and Blood Institute Award--1K01HL145347-01A1, National Institute on Minority Health and Health Disparities (Yale-TCC)--U54MD010711, and National Institute on Minority Health and Health Disparities through the Eastern Caribbean Health Outcomes Research Network (ECHORN)--U24MD006939.

Summary: Background: Artificial Intelligence (AI) has been used to automate detection of retinal diseases from retinal images with great success, in particular for screening for diabetic retinopathy, a major complication of diabetes. Since persons with diabetes routinely receive retinal imaging to evaluate their diabetic retinopathy status, AI-based retinal imaging may have potential to be used as an opportunistic comprehensive screening for multiple systemic micro- and macro-vascular complications of diabetes. Methods: We conducted a qualitative systematic review on published literature using AI on retina images to detect systemic diabetes complications. We searched three main databases: PubMed, Google Scholar, and Web of Science (January 1, 2000, to October 1, 2024). Research that used AI to evaluate the associations between retinal images and diabetes-associated complications, or research involving diabetes patients with retinal imaging and AI systems were included. Our primary focus was on articles related to AI, retinal images, and diabetes-associated complications. We evaluated each study for the robustness of the studies by development of the AI algorithm, size and quality of the training dataset, internal validation and external testing, and the performance. Quality assessments were employed to ensure the inclusion of high-quality studies, and data extraction was conducted systematically to gather pertinent information for analysis. This study has been registered on PROSPERO under the registration ID CRD42023493512. Findings: From a total of 337 abstracts, 38 studies were included. These studies covered a range of topics related to prediction of diabetes from pre-diabetes or non-diabeticindividuals (n = 4), diabetes related systemic risk factors (n = 10), detection of microvascular complications (n = 8) and detection of macrovascular complications (n = 17). Most studies (n = 32) utilized color fundus photographs (CFP) as retinal image modality, while others employed optical coherence tomography (OCT) (n = 6). The performance of the AI systems varied, with an AUC ranging from 0.676 to 0.971 in prediction or identification of different complications. Study designs included cross-sectional and cohort studies with sample sizes ranging from 100 to over 100,000 participants. Risk of bias was evaluated by using the Newcastle–Ottawa Scale and AXIS, with most studies scoring as low to moderate risk. Interpretation: Our review highlights the potential for the use of AI algorithms applied to retina images, particularly CFP, to screen, predict, or diagnose the various microvascular and macrovascular complications of diabetes. However, we identified few studies with longitudinal data and a paucity of randomized control trials, reflecting a gap between the development of AI algorithms and real-world implementation and translational studies. Funding: Dr. Gavin Siew Wei TAN is supported by: 1. DYNAMO: Diabetes studY on Nephropathy And other Microvascular cOmplications II supported by National Medical Research Council (MOH-001327-03): data collection, analysis, trial design 2. Prognositc significance of novel multimodal imaging markers for diabetic retinopathy: towards improving the staging for diabetic retinopathy supported by NMRC Clinician Scientist Award (CSA)–Investigator (INV) (MOH-001047-00).

Background: People with hand osteoarthritis (OA) often have poor access to recommended treatments. To enhance care quality, quality indicators (QIs) based on clinical recommendations are essential. Current QI sets, like the Osteoarthritis Quality Indicator Questionnaire (OA-QI v.2), primarily address hip- and knee OA, and not hand OA. Objectives: To adapt the OA-QI v.2 for assessing patient-reported quality of hand OA care. Design: We used the OA-QI v.2. set as a starting point and adapted it to reflect hand OA care. A literature search was performed to identify potential QIs for hand OA following the Rand/UCLA Appropriateness method. A European expert panel, comprising researchers, clinicians, and patient research partners, participated in online meetings to discuss adaptation and suggest new QIs based on treatment recommendations for hand OA, and anonymously rated each suggested QI regarding its importance, validity, usefulness, and feasibility. Consensus was defined by predefined rating cut-off scores. The adapted questionnaire was translated from English into Norwegian. Cognitive debriefing interviews with Norwegian and UK hand OA patients were conducted to ensure clarity. Results: Our initial literature search provided 1670 articles, with none describing relevant QIs. After three voting rounds, sixteen QI items reached consensus, reflecting current hand OA care standards. Items were generally well understood, requiring only minor clarity amendments after patient interviews (N ​= ​28). Conclusion: The OA-QI v.2 was successfully adapted into a 16-item Hand OA-QI set ensuring alignment with international care standards for hand OA through literature review, international expert panels and patient feedback on language and layout.