Search

Abstract Leukocytes interact with other cells using cell surface receptors. The largest group of such receptors are non-catalytic tyrosine phosphorylated receptors (NTRs), also called immunoreceptors. NTR signalling requires phosphorylation of cytoplasmic tyrosine residues by SRC-family tyrosine kinases. How ligand binding to NTRs induces this phosphorylation, also called NTR triggering, remains controversial, with roles suggested for size-based segregation, clustering, and mechanical force. Here we exploit a recently developed cell-surface generic ligand system to explore the ligand requirements for NTR triggering. We examine the effect of varying the ligand’s length, mobility and valency on the activation of representative members of four NTR families: SIRPβ1, Siglec 14, NKp44 and TREM-1. Increasing the ligand length impairs activation via NTRs, despite enhancing cell-cell conjugation, while varying ligand mobility has little effect on either conjugation or activation. Increasing the valency of the ligand, while enhancing cell-cell conjugation, does not enhance activation at equivalent levels of conjugation. These findings are more consistent with a role for size-based segregation, rather than mechanical force or clustering, in NTR triggering, suggesting a role for the kinetic-segregation model.

Abstract Robotic locomotion in unstructured terrain demands an agile, adaptive, and energy-efficient architecture. To traverse such terrains, legged robots use rigid electromagnetic motors and sensorized drivetrains to adapt to the environment actively. These systems struggle to compete with animals that excel through their agile and effortless motion in natural environments. We propose a bio-inspired musculoskeletal leg architecture driven by antagonistic pairs of electrohydraulic artificial muscles. Our leg is mounted on a boom arm and can adaptively hop on varying terrain in an energy-efficient yet agile manner. It can also detect obstacles through capacitive self-sensing. The leg performs powerful and agile gait motions beyond 5 Hz and high jumps up to 40 % of the leg height. Our leg’s tunable stiffness and inherent adaptability allow it to hop over grass, sand, gravel, pebbles, and large rocks using only open-loop force control. The electrohydraulic leg features a low cost of transport (0.73), and while squatting, it consumes only a fraction of the energy (1.2 %) compared to its conventional electromagnetic counterpart. Its agile, adaptive, and energy-efficient properties would open a roadmap toward a new class of musculoskeletal robots for versatile locomotion and operation in unstructured natural environments.

Abstract Background Pre-exposure prophylaxis (PrEP) is a highly effective pharmaceutical intervention that prevents HIV infection, but PrEP uptake across the US has been slow among men who have sex with men (MSM), especially among Black/African American (B/AA) and Hispanic /Latino (H/L) MSM. This study investigates the acceptability and essential components of a peer-driven intervention (PDI) for promoting PrEP uptake among MSM, with a specific focus on B/AA and H/L communities. Methods We conducted 28 semi-structured, qualitative interviews with MSM in southern New England to explore the components of a PDI, including attitudes, content, and effective communication methods. A purposive sampling strategy was used to recruit diverse participants who reflect the communities with the highest burden of HIV infection. Results Of 28 study participants, the median age was 28 years (interquartile range [IQR]: 25, 35). The sample comprised B/AA (39%, n = 11) and H/L (50%, n = 14) individuals. Notably, nearly half of the participants (46%) were current PrEP users. We found that many participants were in favor of using a PDI approach for promoting PrEP. Additionally, several participants showed interest in becoming peer educators themselves. They emphasized the need for strong communication skills to effectively teach others about PrEP. Moreover, participants noted that peer education should cover key topics like how PrEP works, how effective it is, and any possible side effects. Conclusions Our study shows that effective PDIs, facilitated by well-trained peers knowledgeable about PrEP, could enhance PrEP uptake among MSM, addressing health disparities and potentially reducing HIV transmission in B/AA and H/L communities.

Abstract Photosynthesis is one of the most important biological processes on Earth, providing the main source of bioavailable energy, carbon, and oxygen via the use of sunlight. Despite this importance, the minimum light level sustaining photosynthesis and net growth of primary producers in the global ocean is still unknown. Here, we present measurements from the MOSAiC field campaign in the central Arctic Ocean that reveal the resumption of photosynthetic growth and algal biomass buildup under the ice pack at a daily average irradiance of not more than 0.04 ± 0.02 µmol photons m−2 s−1 in late March. This is at least one order of magnitude lower than previous estimates (0.3–5 µmol photons m−2 s−1) and near the theoretical minimum light requirement of photosynthesis (0.01 µmol photons m−2 s−1). Our findings are based on measurements of the temporal development of the under-ice light field and concurrent measurements of both chlorophyll a concentrations and potential net primary production underneath the sea ice at 86 °N. Such low light requirements suggest that euphotic zones where photosynthesis can occur in the world’s oceans may extend further in depth and time, with major implications for global productivity estimates.

Abstract Aims To synthesise evidence regarding organisational practice environment factors affecting healthcare workforce development, recruitment, and retention in the UK. Methods/data sources A systematic search of PubMed, Web of Science, EMBASE, and PsycINFO yielded ten relevant studies published between 2018 and 2023 and conducted in the UK (the last search was conducted in March 2023). Adhering to The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, two independent reviewers conducted screening, sifting, and data extraction, applying the quality assessment tool for risk of bias. Results Results highlight key factors associated with staff intention to leave/turnover/retention: workplace challenges, aggression, moral distress, on-the-job embeddedness, leadership involvement, organisational support, and flexible shift patterns. Notably, aggression from colleagues, including clinical staff but not interdisciplinary personnel, has a more detrimental impact on staff intention to leave than aggression from patients. Conclusion The complex and context-dependent impacts of these organisational factors on the UK healthcare workforce underscore the need for tailored interventions. The review acknowledges limitations, including bias from excluding qualitative studies, a small pool of included studies, and nurse overrepresentation.

Abstract Renewable energies, such as solar and wind, traditionally suffer from temporal incongruity. Society’s energy demand peaks occur at different times of day than the electricity generation potential of a photovoltaic panel or, often, a wind turbine. Heat demand, in particular, is subject to a significant mismatch between the availability of heat (in the summer) and the need for heat (in the winter). Thus, a future energy system design should incorporate underground thermal energy storage (UTES) to avoid this temporal mismatch and emphasize thermal applications. Such a basis of design would introduce new methods of energy arbitrage, encourage the adoption of geothermal systems, and decrease the carbon intensity of society. UTES techniques are becoming increasingly sophisticated. These methods of storage can range from simple seasonal storage for residential structures in a grouted borehole array (BTES), to aquifer thermal energy storage (ATES), deep reservoir storage (RTES) in basins, among others. The method that each of these techniques shares is the use of the earth as a storage medium. UTES can also be characterized for electricity production, but this work largely explores applications in heating and cooling, further limited in scope to sensible heat storage (SHS). Heating and cooling processes—residential, commercial, and industrial—make up large fractions of energy demand in North America. This is also true of other locales. With the increasing concerns of climate change, exacerbated by anthropogenic greenhouse gas emissions, developers and municipal planners are strategizing to decarbonize building heating and cooling at district scales. This review covers the integration of UTES techniques with thermal energy network (TEN) technology across large districts. Though storage has long been in use for conventional district heating networks, designs are rapidly innovating, indicating broader applications of UTES integration with a TEN is advantageous from both an efficiency and economic perspective. This rapid innovation indicates the need for the integrated review offered in this paper.

In Canada, the task of explaining food prices falls to a handful of grey literature reports that shape media coverage and public understanding and carry significant political and policy influence. We performed an in-depth analysis of fifty-one of these influential reports, including thirty-nine reports by Statistics Canada (including Consumer Price Index reports and other studies) and twelve reports from the Canada Food Price Report (CFPR) series. Our goal was twofold: 1) to identify and classify the various explanations given for food price changes, and 2) to evaluate the scientific rigor of these explanations. We identified 232 total explanations for food price changes, spread across seven thematic categories and thirty-two sub-categories. We find that most claims made in these reports are scientifically incomplete (only 28.6% of all claims meet established criteria for the completeness of scientific arguments). We also identify a lack of comprehensiveness in the areas of emphasis and the claims being presented and drivers being explored, particularly with respect to issues presently at the centre of food price discourse in Canada, such as the agency of grocers and other supply chain actors, corporate growth imperatives, and climate change. Considering the importance of food prices and food security to prosperity and well-being in Canada, we conclude with a series of recommendations for strengthening the scientific rigor of these reports, including greater inclusion of supporting evidence, opportunities for peer review, and increased transparency regarding conflicts of interest and funding sources.

Abstract Chronic kidney disease (CKD) is a global public health problem with major human and economic consequences. Despite advances in clinical guidelines, classification systems and evidence-based treatments, CKD remains underdiagnosed and undertreated and is predicted to be the fifth leading cause of death globally by 2040. This review aims to identify barriers and enablers to the effective detection, diagnosis, disclosure and management of CKD since the introduction of the Kidney Disease Outcomes Quality Initiative (KDOQI) classification in 2002, advocating for a renewed approach in response to updated Kidney Disease: Improving Global Outcomes (KDIGO) 2024 clinical guidelines. The last two decades of improvements in CKD care in the UK are underpinned by international adoption of the KDIGO classification system, mixed adoption of evidence-based treatments and research informed clinical guidelines and policy. Interpretation of evidence within clinical and academic communities has stimulated significant debate of how best to implement such evidence which has frequently fuelled and frustratingly forestalled progress in CKD care. Key enablers of effective CKD care include clinical classification systems (KDIGO), evidence-based treatments, electronic health record tools, financially incentivised care, medical education and policy changes. Barriers to effective CKD care are extensive; key barriers include clinician concerns regarding overdiagnosis, a lack of financially incentivised care in primary care, complex clinical guidelines, managing CKD in the context of multimorbidity, bureaucratic burden in primary care, underutilisation of sodium-glucose co-transporter-2 inhibitor (SGLT2i) medications, insufficient medical education in CKD, and most recently – a sustained disruption to routine CKD care during and after the COVID-19 pandemic. Future CKD care in UK primary care must be informed by lessons of the last two decades. Making step change, over incremental improvements in CKD care at scale requires a renewed approach that addresses key barriers to detection, diagnosis, disclosure and management across traditional boundaries of healthcare, social care, and public health. Improved coding accuracy in primary care, increased use of SGLT2i medications, and risk-based care offer promising, cost-effective avenues to improve patient and population-level kidney health. Financial incentives generally improve achievement of care quality indicators – a review of financial and non-financial incentives in CKD care is urgently needed.

Introduction: Membranoproliferative glomerulonephritis (MPGN) is a pattern of injury seen on kidney biopsy, with various underlying etiologies. The component types, including complement-mediated MPGN, are relatively rare. This study presents longitudinal real-world data over 20 years in a tertiary renal center in the UK. Methods: All patients with an MPGN pattern on kidney biopsy between 2000 and 2020 were identified. After applying exclusion criteria, 38 patients remained. Data including patient demographics, details of the renal histology from the kidney biopsy, baseline laboratory results, treatments received, and clinical outcomes including renal replacement therapy and death were collected from the organization’s electronic patient record. Results: Twenty-eight of the cohort had immune complex-mediated MPGN, and 10 had complement-mediated MPGN (8 with C3 glomerulonephritis and 2 with dense deposit disease). Median follow-up was 72 months. Median age was 61 years. Overall, 60.5% were female, and 92.1% white. At presentation, median eGFR was 31.5 mL/min/1.73 m2 and uPCR 394 mg/mmol. Here, 78.9% received renin-angiotensin-aldosterone system inhibitors and 71.1% received any immunosuppression. In total, 47.4% progressed to ESKD and 50% died during follow-up. Conclusions: The study found an older patient population than typically reported. Poor outcomes were observed in the overall cohort with progression to ESKD and mortality both at almost 50%. This may be influenced by the older patient population. Individualized management of patients with an MPGN biopsy finding is paramount, with comprehensive evaluation for triggers and complement abnormalities. Going forward, registry enrolment and collaborative studies may enhance knowledge and outcomes.

Psychoactive substance misuse tends to affect the social, economic, and mental health of young adult users and their parents. However, there is currently limited research on the challenges of parents of young adults who misuse psychoactive substances. The stress-strain-coping-support theoretical model was used to assess the challenges parents of young adults who misuse psychoactive substances encounter in Ghana. Based on interpretive phenomenology, we purposively sampled and conducted in-depth interviews with 15 parents from the Adum-Banso Health Centre. Data was processed with NVivo 12 pro data and analysed thematically with four stages of Interpretative Phenomenological Analysis (IPA). The challenges of parents of young adults engaged in psychoactive substance misuse included financial constraints, the onset of negative emotional effects on parents, structural challenges in pursuit of medical treatment, and stigma and discrimination. We have provided empirical data to inform policy decisions on establishing social protection and psychosocial support schemes for young adults misusing psychoactive substances and their parents to enhance the rehabilitation of young adults recovering from the impacts of psychoactive substance misuse.

Abstract Introduction Rheumatoid arthritis (RA) guidelines recommend methotrexate (MTX)-anchored therapy with biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs); however, tolerability issues often lead to non-adherence. Canadian data on MTX tapering and/or withdrawal following b/tsDMARD initiation are minimal. This chart review assessed frequency of MTX tapering or withdrawal following b/tsDMARD initiation and the impact on disease status in Canadian adults with RA. Methods Eligible patients had received MTX for ≥ 3 months before b/tsDMARD initiation. The b/tsDMARD was prescribed continuously for ≥ 18 months. Patients taking > 10 mg/day oral prednisone or equivalent were excluded. Results Eight hundred eighty-nine patients (mean baseline MTX dose 19.0 mg/week) prescribed b/tsDMARDs (tumor necrosis factor inhibitor 52.1%, Janus kinase inhibitor 18.3%, interleukin-6 inhibitor [IL-6i] 11.9%, other 17.7%) were evaluated at 22 Canadian centers. Within 2 years of b/tsDMARD initiation, MTX was tapered in 123 (13.8%) patients and discontinued in 147 (16.5%), most commonly due to planned tapering (36.6%) and patient decision (27.2%), respectively, and most commonly with IL-6i use (34.9%). The MTX dose was unchanged for 582 (65.5%) patients and increased for 37 (4.2%). Missing data limit interpretations of MTX dose effects on some secondary endpoints and challenge the assertion that a disease activity measure–based treat-to-target approach is routinely used in Canadian rheumatology practice. Conclusions Methotrexate tapering or withdrawal occurred in 30.4% of Canadians with RA within 2 years following b/tsDMARD initiation. Baseline disease activity measures were missing from many medical records. However, for patients with baseline assessments, MTX tapering or discontinuation did not worsen disease activity.

Abstract Machine learning (ML) has transformed protein engineering by constructing models of the underlying sequence-function landscape to accelerate the discovery of new biomolecules. ML-guided protein design requires models, trained on local sequence-function information, to accurately predict distant fitness peaks. In this work, we evaluate neural networks’ capacity to extrapolate beyond their training data. We perform model-guided design using a panel of neural network architectures trained on protein G (GB1)-Immunoglobulin G (IgG) binding data and experimentally test thousands of GB1 designs to systematically evaluate the models’ extrapolation. We find each model architecture infers markedly different landscapes from the same data, which give rise to unique design preferences. We find simpler models excel in local extrapolation to design high fitness proteins, while more sophisticated convolutional models can venture deep into sequence space to design proteins that fold but are no longer functional. We also find that implementing a simple ensemble of convolutional neural networks enables robust design of high-performing variants in the local landscape. Our findings highlight how each architecture’s inductive biases prime them to learn different aspects of the protein fitness landscape and how a simple ensembling approach makes protein engineering more robust.

Abstract Rationale & objective Glomerulonephritis (GN) is a leading cause of chronic kidney disease (CKD). Major adverse cardiovascular events (MACE) are prolific in CKD. The risk of MACE in GN cohorts is multifactorial. We investigated the prognostic significance of routine cardiac biomarkers, Troponin I and N-terminal pro-BNP (NT-proBNP) in predicting MACE within 5 years of GN diagnosis. Study Design Retrospective cohort study. Setting & participants Data were obtained from TriNetX, a global federated health research network of electronic health records (EHR). Exposure or predictor Biomarker thresholds: Troponin I: 18 ng/L, NT-proBNP: 400 pg/mL. Outcomes Primary outcome: Incidence of major adverse cardiovascular events (MACE). Secondary outcome: was the risk for each individual component of the composite outcome. Analytical Approach 1:1 propensity score matching using logistic regression. Cox proportional hazard models were used to assess the association of cardiac biomarkers with the primary and secondary outcomes, reported as Hazard Ratio (HR) and 95% confidence intervals (CI). Survival analysis was performed which estimates the probability of an outcome over a 5-year follow-up from the index event. Results Following PSM, 34,974 and 18,218 patients were analysed in the Troponin I and NTproBNP cohorts, respectively. In the Troponin I all cause GN cohort, 3,222 (9%) developed composite MACE outcome HR 1.79; (95% CI, 1.70, 1.88, p

Abstract When sex chromosomes evolve recombination suppression, the sex-limited chromosome (Y/W) commonly degenerate by losing functional genes. The rate of Y/W degeneration is believed to slow down over time as the most essential genes are maintained by purifying selection, but supporting data are scarce especially for ZW systems. Here, we study W degeneration in Sylvioidea songbirds where multiple autosomal translocations to the sex chromosomes, and multiple recombination suppression events causing separate evolutionary strata, have occurred during the last ~ 28.1–4.5 million years (Myr). We show that the translocated regions have maintained 68.3–97.7% of their original gene content, compared to only 4.2% on the much older ancestral W chromosome. By mapping W gene losses onto a dated phylogeny, we estimate an average gene loss rate of 1.0% per Myr, with only moderate variation between four independent lineages. Consistent with previous studies, evolutionarily constrained and haploinsufficient genes were preferentially maintained on W. However, the gene loss rate did not show any consistent association with strata age or with the number of W genes at strata formation. Our study provides a unique account on the pace of W gene loss and reinforces the significance of purifying selection in maintaining essential genes on sex chromosomes.

Abstract Introduction Tuberculosis is a global health problem that causes 1. 4 million deaths every year. It has been estimated that sputum smear-negative diagnosis but culture-positive pulmonary TB diagnosis contribute to 12.6% of pulmonary TB transmission. TB diagnosis by smear microscopy smear has a minimum detection limit (LOD) of 5,000 to 10,000 bacilli per milliliter (CFU/ml) of sputum result in missed cases and false positives. However, GeneXpert technology, with a LOD of 131–250 CFU/ml in sputum samples and its implementation is believe to facilitate early detection TB and drug-resistant TB case. Since 2013, Ghana health Service (GHS) introduce GeneXpert MTB/RIF diagnostic in all regional hospitals in Ghana, however no assessment of performance between microscopy and GeneXpert TB diagnosis cross the health facilities has been reported. The study compared the results of routine diagnoses of TB by microscopy and Xpert MTB from 2016 to 2020 at the Cape Coast Teaching Hospital (CCTH). Methods The study compared routine microscopic and GeneXpert TB diagnosis results at the Cape Coast Teaching Hospital (CCTH) from 2016 to 2020 retrospectively. Briefly, sputum specimens were collected into 20 mL sterile screw-capped containers for each case of suspected TB infection and processed within 24 h. The samples were decontaminated using the NALC-NaOH method with the final NaOH concentration of 1%. The supernatants were discarded after the centrifuge and the remaining pellets dissolved in 1–1.5 ml of phosphate buffer saline (PBS) and used for diagnosis. A fixed smears were Ziehl-Neelsen acid-fast stain and observed under microscope and the remainings were used for GeneXpert MTB/RIF diagnosis. The data were analyze using GraphPad Prism. Results 50.11% (48.48–51.38%) were females with an odd ratio (95% CI) of 1.004 (0.944–1.069) more likely to report to the TB clinic for suspected TB diagnosis. The smear-positive cases for the first sputum were 6.6% (5.98–7.25%), and the second sputum was 6.07% (5.45–6.73%). The Xpert MTB-RIF diagnosis detected 2.93% (10/341) (1.42–5.33%) in the first and 5.44% (16/294) (3.14–8.69%) in the second smear-negative TB samples. The prevalence of Xpert MTB-RIF across smear positive showed that males had 56.87% (178/313) and 56.15% (137/244) and females had 43.13% (135/313) and 43.85% (107/244) for the first and second sputum. Also, false negative smears were 0.18% (10/5607) for smear 1 and 0.31% (16/5126) for smear 2. Conclusion In conclusion, the study highlights the higher sensitivity of the GeneXpert assay compared to traditional smear microscopy for detecting MTB. The GeneXpert assay identified 10 and 16 positive MTB from smear 1 and smear 2 samples which were microscopic negative.

Abstract Background Severe trauma is associated with systemic inflammation and organ dysfunction. Preclinical rodent trauma models are the mainstay of postinjury research but have been criticized for not fully replicating severe human trauma. The aim of this study was to create a rat model of multicompartmental injury which recreates profound traumatic injury. Methods Male Sprague–Dawley rats were subjected to unilateral lung contusion and hemorrhagic shock (LCHS), multicompartmental polytrauma (PT) (unilateral lung contusion, hemorrhagic shock, cecectomy, bifemoral pseudofracture), or naïve controls. Weight, plasma toll‐like receptor 4 (TLR4), hemoglobin, spleen to body weight ratio, bone marrow (BM) erythroid progenitor (CFU‐GEMM, BFU‐E, and CFU‐E) growth, plasma granulocyte colony‐stimulating factor (G‐CSF) and right lung histologic injury were assessed on day 7, with significance defined as p values

Abstract Patient-derived xenograft (PDX) models are widely used in cancer research. To investigate the genomic fidelity of non-small cell lung cancer PDX models, we established 48 PDX models from 22 patients enrolled in the TRACERx study. Multi-region tumor sampling increased successful PDX engraftment and most models were histologically similar to their parent tumor. Whole-exome sequencing enabled comparison of tumors and PDX models and we provide an adapted mouse reference genome for improved removal of NOD scid gamma (NSG) mouse-derived reads from sequencing data. PDX model establishment caused a genomic bottleneck, with models often representing a single tumor subclone. While distinct tumor subclones were represented in independent models from the same tumor, individual PDX models did not fully recapitulate intratumor heterogeneity. On-going genomic evolution in mice contributed modestly to the genomic distance between tumors and PDX models. Our study highlights the importance of considering primary tumor heterogeneity when using PDX models and emphasizes the benefit of comprehensive tumor sampling.

The current study investigated the geochemical characterization and contamination of groundwater quality in Tarkwa, a mining community in Ghana. Total dissolved solids, electrical conductivity, calcium, magnesium, sodium, potassium, total dissolved solids, total hardness, heavy metals, and cyanide (CN) were all assessed in 74 groundwater samples. Other parameters assessed included pH, electrical conductivity, carbonate, bicarbonate, chloride, sulphate, nitrate, and pH. Using the method recommended by the USEPA, a health risk assessment was carried out. Among the parameters which exceeded their WHO recommended threshold were pH (4.9–7.7), Conductivity (150–1082 µS/Cm), Turbidity (1.4–139.5 NTU), Magnesium (1.9–395.5 mg/L), Nitrate (4.5 mg/L–760 mg/L), phosphate (2.3–80 mg/L), Sulphate (10–855.6 mg/L), CN (1.6–16 mg/L), As (0.001–0.015 mg/L), Hg (0.001–0.005 mg/L), Cd (ND-0.009 mg/L), Mn (0.004–1.38 mg/L), Ni (0.002–0.118 mg/L). The study also showed that the groundwater in Tarkwa is naturally hard, making Ca and Mg ions the main ions determining the chemistry of the water. Similar to this, the most significant factors affecting water chemistry were rock dominance and precipitation dominance. Due to high levels of CN, As, and Cd, health risk evaluation revealed that prolonged intake of groundwater from Tarkwa is linked to both carcinogenic and noncarcinogenic health risk. Children were shown to be more vulnerable to both carcinogenic and noncarcinogenic health risks than adults.

Objective To highlight progress in facilitating and supporting pan-Canadian data analysis research that is supported by a central coordinating center. This process will be illustrated with the use of a recently completed project that has been supported using data from Alberta, British Columbia, and Ontario. Approach The project represents a significant endeavor within the central coordinating center, as it necessitates coordination for data access, data importation and analytical support across three provinces. The focus will be on the administrative processes refined to support collaborative research endeavors. While specific project details will remain undisclosed, procedural enhancements within the central coordinating center framework will be highlighted. Key discussion points include standardized protocols for data access, collaborative efforts to streamline data importation, and facilitation of analytical support across jurisdictions. The type of cross-jurisdictional analytic support will as well be highlighted; data variables harmonization and sharing of data algorithms cohorts across the participating provincial data centers in support of the meta-analysis. Results The successful completion of the final data analysis underscores the effectiveness of a unified data access coordination center for researchers seeking multi-regional health data in Canada. By highlighting advancements enabled by the central coordinating center and provincial data centers, this submission aims to inform researchers about the current landscape of pan-Canadian research and foster opportunities for future collaboration. Implications Sharing insights and lessons from this project emphasizes the advancements facilitated by the central coordinating center and provincial data centers, informing researchers about the potential of pan-Canadian research, and encouraging future collaborative endeavors.

Objective To highlight the partnership between the Canadian Partnership for Tomorrow’s Health (CanPath) and Health Data Research Network (HDRN Canada), which enables researchers to link CanPath’s health and lifestyle survey data to health records and related data across multiple regions. Background CanPath is a population health study of over 350,000 Canadians from seven regional cohorts across all ten provinces, making it one of the world's largest population cohorts. HDRN Canada is a network of member organizations, including provincial, territorial, and pan-Canadian data centres. Approach This partnership leveraged collective expertise and resources to facilitate the linkage of CanPath’s harmonized data to multi-regional health and health-related administrative data held at HDRN Canada’ s data centres. Researchers can access these data for multi-regional projects through HDRN Canada’s Data Access Support Hub, which provides a single access portal. Results Researchers were able to successfully link CanPath’s survey data to provincial administrative health data. The collaboration’s streamlined process for data access enhances efficiency and facilitates pan-Canadian population health research. Conclusion This collaboration demonstrates the feasibility and value of linking population health datasets while demonstrating the challenges and opportunities associated with accessing national administrative health data within a federated health data system. Implications The partnership between CanPath and HDRN Canada has significant implications for advancing population health research in Canada. By providing researchers with access to linked data from diverse sources, the partnership enables comprehensive investigations into health determinants, disease patterns, and clinical outcomes. This enhances the scope and depth of population health research in Canada, thereby leading to a better understanding of the most pressing health challenges.

IntroductionSchistosomiasis, a tropical parasitic disease, affects 779 million people globally, with 85% of cases in Africa. The interplay between schistosomiasis and other sexually transmitted infections (STIs) can exacerbate health burdens, but most attention has focused on interactions with HIV, neglecting coinfections with other STIs. This systematic review and meta-analysis aims to understand the role Schistosoma infections play in STIs within schistosomiasis-endemic populations.MethodsThe study is a systematic review and meta-analysis investigating the link between Schistosoma infections and STIs in endemic regions. It uses PRISMA guidelines, electronic databases, and Google Scholar to assess prevalence, associations, and heterogeneity, reducing bias using a Meta-Mar statistical tool.ResultsA quantitative synthesis of 33 articles from 1975–2024 involved 22,587 participants from 13 countries, including regions in Africa, France, and China, examining coinfections of schistosomiasis and STIs, including HIV. The pooled estimates showed a significant risk association between schistosomiasis and STIs [RR (95% CI) = 1.18, (1.13–1.24); z/t = 7.55, p

Camera trapping networks have the potential to monitor wildlife diversity at large scales. However, their efficacy in detecting different species varies, leading to considerable disparities in population density estimates. Furthermore, species of different trophic levels and body sizes naturally occur at different densities, challenging the evenness assumptions inherent in conventional diversity indices. Here we present a novel index: Fractional Richness, which is specifically designed for application in extensive camera trap networks. The index addresses situations where evenness is uninformative, for example in communities characterized by multiple trophic levels, diverse body sizes, variable population densities, or other complications. To determine the effectiveness of our Fractional Richness index, we modeled spatial patterns of Shannon diversity, species richness, and Fractional Richness for two wildlife communities in Wisconsin USA to quantitatively measure which index best reflected ecologically relevant landscape patterns. One community was much more uneven than the other, with detection rates ranging across three orders of magnitude. The more even community could be modeled accurately with both Shannon diversity and Fractional Richness, but the highly uneven community could only be modeled accurately with Fractional Richness. Maximum population density varies by species, and most wildlife survey methods are not equally capable of detecting all species. In communities with both high and low-density species, or when detectability varies, evenness may not be the most informative measure. In these situations, Fractional Richness may be a more suitable index.

Background: Preterm delivery is associated with neonatal complications such as neurological impairment and necrotising enterocolitis. Thus, suppression of early myometrial contractility in pre-term labor (PTL) delays delivery and reduces maternal adverse outcomes associated with PTL. However, most tocolytics exert varied efficacies and untoward outcomes such as maternal cardiovascular and respiratory effects creating a need for novel efficacious and safe tocolytics. We previously reported that chlorophyll derivatives including Pheophorbide-a (PBa) isolated from the leaves of the plant Ficus exasperata, effectively inhibited non-pregnant mouse myometrial contractility ex vivo. Therefore, the current study explores the mechanisms involved in PBa-induced myometrial contractility inhibition in both non-pregnant and pregnant mouse uterus. Method: We carried out contractility studies by inducing isometric tension on isolated myometrial strips of mice following ex vivo exposure to PBa. The uterine strips were mounted in organ baths containing oxygenated physiological saline maintained at pH 7.4 and 36.8 ± 0.2 °C. Results: PBa (0.02–206.19 µM) produced concentration-dependent decreases in the amplitude and frequency of pregnant and non-pregnant uterine contractions. In addition, PBa (87.74 μM) significantly inhibited the amplitude (P = 0.0026) and frequency (P = 0.0178) of OT-induced uterine contractility in Ca2+−free solution and in the presence of high KCl (80 mM) (P = 0.005). Furthermore, our study showed that the uterine relaxant effect of PBa occurred through the blockade of l-type voltage-gated Ca2+channels (VGCCs) and through inhibition of Ca2+ mobilization from intracellular stores which are common downstream pathways specific to tocolytics and relevant for uterine relaxation. Conclusion: These findings reveal that PBa effectively attenuates uterine contractions via interaction with Ca2+−entry and shows potential as a promising candidate as a tocolytic therapy for PTL. Further investigations on PBa are encouraged to elucidate molecular and cellular mechanisms of PBa uterine relaxation activity including assessment of efficacy and off-target effects.

Abstract BackgroundLittle is known about how best to reach people with social marketing messages promoting use of clinical HIV and sexually transmitted infection (STI) services. ObjectiveWe evaluated a multiplatform, digital social marketing campaign intended to increase use of HIV/STI testing, treatment, and prevention services among gay, bisexual, and other men who have sex with men (MSM) at an LGBTQ+ (lesbian, gay, bisexual, transgender, queer, and/or questioning) community health center. MethodsWe evaluated engagement with a social marketing campaign launched by Open Door Health, the only LGBTQ+ community health center in Rhode Island, during the first 8 months of implementation (April to November 2021). Three types of advertisements encouraging use of HIV/STI services were developed and implemented on Google Search, Google Display, Grindr, and Facebook. Platforms tracked the number of times that an advertisement was displayed to a user (impressions), that a user clicked through to a landing page that facilitated scheduling (clicks), and that a user requested a call to schedule an appointment from the landing page (conversions). We calculated the click-through rate (clicks per impression), conversion rate (conversions per click), and the dollar amount spent per 1000 impressions and per click and conversion. ResultsOverall, Google Search yielded the highest click-through rate (7.1%) and conversion rate (7.0%) compared to Google Display, Grindr, and Facebook (click-through rates=0.4%‐3.3%; conversion rates=0%‐0.03%). Although the spend per 1000 impressions and per click was higher for Google Search compared to other platforms, the spend per conversion—which measures the number of people intending to attend the clinic for services—was substantially lower for Google Search (US $48.19 vs US $3120.42-US $3436.03). ConclusionsCampaigns using the Google Search platform may yield the greatest return on investment for engaging MSM in HIV/STI services at community health clinics. Future studies are needed to measure clinical outcomes among those who present to the clinic for services after viewing campaign advertisements and to compare the return on investment with use of social marketing campaigns relative to other approaches.

The degree to which artificial intelligence healthcare research is informed by data and stakeholders from community settings has not been previously described. As communities are the principal location of healthcare delivery, engaging them could represent an important opportunity to improve scientific quality. This scoping review systematically maps what is known and unknown about community-engaged artificial intelligence research and identifies opportunities to optimize the generalizability of these applications through involvement of community stakeholders and data throughout model development, validation, and implementation. Embase, PubMed, and MEDLINE databases were searched for articles describing artificial intelligence or machine learning healthcare applications with community involvement in model development, validation, or implementation. Model architecture and performance, the nature of community engagement, and barriers or facilitators to community engagement were reported according to PRISMA extension for Scoping Reviews guidelines. Of approximately 10,880 articles describing artificial intelligence healthcare applications, 21 (0.2%) described community involvement. All articles derived data from community settings, most commonly by leveraging existing datasets and sources that included community subjects, and often bolstered by internet-based data acquisition and subject recruitment. Only one article described inclusion of community stakeholders in designing an application-a natural language processing model that detected cases of likely child abuse with 90% accuracy using harmonized electronic health record notes from both hospital and community practice settings. The primary barrier to including community-derived data was small sample sizes, which may have affected 11 of the 21 studies (53%), introducing substantial risk for overfitting that threatens generalizability. Community engagement in artificial intelligence healthcare application development, validation, or implementation is rare. As healthcare delivery occurs primarily in community settings, investigators should consider engaging community stakeholders in user-centered design, usability, and clinical implementation studies to optimize generalizability.

CONTEXT:. Sepsis leads to multiple organ dysfunction and negatively impacts patient outcomes. Skeletal muscle disuse is a significant comorbidity in septic patients during their ICU stay due to prolonged immobilization. HYPOTHESIS:. Combination of sepsis and muscle disuse will promote a unique proteomic signature in skeletal muscle in comparison to disuse and sepsis separately. METHODS AND MODELS:. Following cecal ligation and puncture (CLP) or Sham surgeries, mice were subjected to hindlimb suspension (HLS) or maintained normal ambulation (NA). Tibialis anterior muscles from 24 C57BL6/J male mice were harvested for proteomic analysis. Proteomic profiles were assessed using nano-liquid chromatography with tandem mass spectrometry, followed by data analysis including Partial Least Squares Discriminant Analysis (PLS-DA), to compare the differential protein expression across groups. RESULTS:. A total of 2876 differentially expressed proteins were identified, with marked differences between groups. In mice subjected to CLP and HLS combined, there was a distinctive proteomic signature characterized by a significant decrease in the expression of proteins involved in mitochondrial function and muscle metabolism, alongside a marked increase in proteins related to muscle degradation pathways. The PLS-DA demonstrated a clear separation among experimental groups, highlighting the unique profile of the CLP/HLS group. This suggests an important interaction between sepsis-induced inflammation and disuse atrophy mechanisms in sepsis-induced myopathy. INTERPRETATIONS AND CONCLUSIONS:. Our findings reveal a complex proteomic landscape in skeletal muscle exposed to sepsis and disuse, consistent with an exacerbation of muscle protein degradation under these combined stressors. The identified proteins and their roles in cellular stress responses and muscle pathology provide potential targets for intervention to mitigate muscle dysfunction in septic conditions, highlighting the importance of addressing both sepsis and disuse concurrently in clinical and experimental settings.

Background:. Surrogates, proxies, and clinicians making shared treatment decisions for patients who have lost decision-making capacity often fail to honor patients’ wishes, due to stress, time pressures, misunderstanding patient values, and projecting personal biases. Advance directives intend to align care with patient values but are limited by low completion rates and application to only a subset of medical decisions. Here, we investigate the potential of large language models (LLMs) to incorporate patient values in supporting critical care clinical decision-making for incapacitated patients in a proof-of-concept study. Methods:. We simulated text-based scenarios for 50 decisionally incapacitated patients for whom a medical condition required imminent clinical decisions regarding specific interventions. For each patient, we also simulated five unique value profiles captured using alternative formats: numeric ranking questionnaires, text-based questionnaires, and free-text narratives. We used pre-trained generative LLMs for two tasks: 1) text extraction of the treatments under consideration and 2) prompt-based question-answering to generate a recommendation in response to the scenario information, extracted treatment, and patient value profiles. Model outputs were compared with adjudications by three domain experts who independently evaluated each scenario and decision. Results and Conclusions:. Automated extractions of the treatment in question were accurate for 88% (n = 44/50) of scenarios. LLM treatment recommendations received an average Likert score by the adjudicators of 3.92 of 5.00 (five being best) across all patients for being medically plausible and reasonable treatment recommendations, and 3.58 of 5.00 for reflecting the documented values of the patient. Scores were highest when patient values were captured as short, unstructured, and free-text narratives based on simulated patient profiles. This proof-of-concept study demonstrates the potential for LLMs to function as support tools for surrogates, proxies, and clinicians aiming to honor the wishes and values of decisionally incapacitated patients.

Abstract Climate‐smart agriculture (CSA) serves as a credible mechanism to simultaneously address food security, climate change, and agricultural productivity. Despite the widespread adoption of CSA approaches across West Africa, many countries have still not been able to resolve the problems of food insecurity and rural poverty. This systematic review evaluates published evidence on the types of CSA practices, the determinants and benefits of adoption, and the barriers confronting the adoption of CSA practices across West Africa, following the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses statement checklist. Articles published in English from January 2010 to March 2023 investigating the benefits of and barriers to the adoption of CSA practices in West Africa were retrieved from ScienceDirect, Web of Science, and Scopus databases. The methodological quality of studies was assessed using Joanna Briggs Institute critical appraisal tools for use in systematic reviews. The themes emerging from the articles were extracted, and a summary was provided to illustrate each theme. After applying the eligibility criteria, 12 articles were included in the final review. The studies reviewed revealed that farmers used more knowledge‐, water‐, carbon‐, and nitrogen‐smart practices, compared to weather‐ and energy‐smart practices. Across the reviewed papers, factors such as the education level of farmers, age, gender, household size, membership of a social group, agricultural extension services, and access to credit/financial resources influenced CSA adoption. The reviewed studies identified that farmers who used CSA practices reported benefits such as improved soil fertility, higher yield, improved household income, climate resilience (such as overcoming the effects of drought and extreme temperatures), and food security. Some farmers adopted CSA practices to reduce the effect of droughts and high temperatures on their crops, and thus increase their resilience to climate variability and change. However, farmers’ adoption is confronted with challenges related to the technicality of some CSA practices, high cost of labor for CSA implementation, lack of credit and government support, limited access to weather and climate information, limited information about CSA options, high illiteracy level of smallholder farmers, and incompatibility of some practices with farmers’ crop of interest. Our findings show that most CSA practices in the studies we reviewed are not well targeted to meet farmers’ crop of interest, and that governments should provide more practical training to enhance farmers’ understanding of CSA practices, especially those related to weather‐ and energy‐smart initiatives. There should also be more robust financial and institutional support to improve the adoption and usage of CSA practices at all levels. Additionally, socio‐cultural factors such as values, customs, and beliefs should be properly integrated into CSA plans as they influence the adoption of CSA practices.

Purpose To address emerging nutritional epidemiological research questions, data from contemporary cohorts are needed. CARTaGENE is the largest ongoing prospective cohort study of men and women in Québec, Canada. Dietary information was collected making it a rich resource for the exploration of diet in the aetiology of many health outcomes.Participants CARTaGENE recruited over 43 000 men and women aged 40–69 in two phases (A and B). In phase A, a total of 19 784 men and women were enrolled between 2009 and 2010. In 2011–2012, phase A participants of CARTaGENE were recontacted and invited to complete the self-administered Canadian Diet History Questionnaire II, which assessed usual intake over the past 12 months of a comprehensive array of foods, beverages and supplements; 9379 participants with non-missing age and sex data and with plausible total energy intake comprise the CARTaGENE Cohort Nutrition Study (4212 men; 5167 women).Findings to date Available dietary data include intake of total energy, macronutrients and micronutrients, food group equivalents and a measure of diet quality based on the Canadian Healthy Eating Index 2005 (C-HEI 2005). Intake and diet quality varied among participants though they generally met the recommended dietary reference intakes for most nutrients. The mean C-HEI 2005 score was 61.5 (SD=14.0; max score=100), comparable to the general Canadian population. The mean (SD) scores for men and women separately were 57.0 (14.1) and 65.2 (12.8), respectively. C-HEI scores were higher for never smokers (61.6), those who had attained more than a high school education (61.4) and those with high physical activity (60.4) compared with current smokers (55.8), less than high school education level (56.2) and low physical activity (57.6), respectively (p values

BackgroundImmunocompromised individuals are known to respond inadequately to SARS-CoV-2 vaccines, placing them at high risk of severe or fatal COVID-19. Thus, immunocompromised individuals and their caregivers may still practice varying degrees of social or physical distancing to avoid COVID-19. However, the association between physical distancing to avoid COVID-19 and quality of life has not been comprehensively evaluated in any study. ObjectiveWe aim to measure physical distancing behaviors among immunocompromised individuals and the association between those behaviors and person-centric outcomes, including health-related quality of life (HRQoL) measures, health state utilities, anxiety and depression, and work and school productivity impairment. MethodsA patient-informed protocol was developed to conduct the EAGLE Study, a large cross-sectional, observational study, and this paper describes that protocol. EAGLE is designed to measure distancing behaviors and outcomes in immunocompromised individuals, including children (aged ≥6 mo) and their caregivers, and nonimmunocompromised adults in the United States and United Kingdom who report no receipt of passive immunization against COVID-19. We previously developed a novel self- and observer-reported instrument, the Physical Distancing Scale for COVID-19 Avoidance (PDS-C19), to measure physical distancing behavior levels cross-sectionally and retrospectively. Using an interim or a randomly selected subset of the study population, the PDS-C19 psychometric properties will be assessed, including structural validity, internal consistency, known-group validity, and convergent validity. Associations (correlations) will be assessed between the PDS-C19 and validated HRQoL-related measures and utilities. Structural equation modeling and regression will be used to assess these associations, adjusting for potential confounders. Participant recruitment and data collection took place from December 2022 to June 2023 using direct-to-patient channels, including panels, clinician referral, patient advocacy groups, and social media, with immunocompromising diagnosis confirmation collected and assessed for a randomly selected 25% of immunocompromised participants. The planned total sample size is 3718 participants and participant-caregiver pairs. Results will be reported by immunocompromised status, immunocompromising condition category, country, age group, and other subgroups. ResultsAll data analyses and reporting were planned to be completed by December 2023. Results are planned to be submitted for publication in peer-reviewed journals in 2024-2025. ConclusionsThis study will quantify immunocompromised individuals’ physical distancing behaviors to avoid COVID-19 and their association with HRQoL as well as health state utilities. International Registered Report Identifier (IRRID)RR1-10.2196/52643

A timing and precise diagnosis of crop nutrient status is essential for optimizing management practices that promote environmentally friendly and enhanced crop yields. Although plant tissue analysis has conventionally been employed to evaluate the nutritional status of crops, this method cannot capture the spatial variability of crop nutrients. In contrast, satellite-based remote sensing can monitor the nutrient status of crops across expansive areas. This study explored the capability of multi-source satellite images (PlanetScope-4: 3 m, 4 bands; PlanetScope-8: 3 m, 8 bands; Sentinel-2: 10–60 m, 13 bands; PRISMA: 30 m, 239 bands) in mapping 12 foliar nutrients in cranberries. Three machine learning approaches, including partial least squared regression (PLSR), support vector regression (SVR), random forest regression (RFR), were used to relate foliar nutrients to different types of satellite-derived features (SR: surface reflectance; VI: vegetation indices; TF: texture features) or their combinations (SR+VI, VI+TF and SR+VI+TF). Model performance was compared across different foliar nutrients, modelling approaches and combinations of model input features using R2 (the coefficient of determination) and RRMSE (relative root mean square error, = root mean square error/nutrient range × 100 %). Input features that were important to foliar nutrient modelling were identified. The model performance difference among nutrients was consistent between Planet-4 and Sentinel-2, as well as between Planet-8 and PRISMA. In the Planet-4 and Sentinel-2 derived models, N was best predicted (average R2 = 0.77, average RRMSE=15 %), followed by macronutrients S (0.60–0.63, 11 %), Mg (0.58–0.65, 10–11 %), Ca (0.49–0.51, 9 %), Na (0.69, 22 %), P (0.49, 9 %) and K (0.20, 8 %), and then by all micronutrients(i.e., Fe, Mn, B, Cu and Zn: R2 = 0.04–0.61; RRMSE=16–28 %). In the Planet-8 and PRISMA derived models, macronutrients (i.e., N, P, K, Mg, Ca, S and Na) had lower R2 and RRMSE (R2 = 0.06–0.59; RRMSE=7–57 %) than micronutrients (i.e., Fe, Mn, B, Cu and Zn: R2 = 0.18–0.60; RRMSE=19–66 %). The successful retrieval of foliar nutrients from satellite imagery was influenced by many factors, including the intercorrelation between nutrients and model input features, the data availability at critical growth stages, and satellite images characteristics (e.g., spatial and spectral resolutions). Except for foliar nitrogen, foliar nutrients typically do not exhibit distinct absorption features associated with C, H, N, or O molecular bonds in the 400–2500 nm range. Our results indicate that their successful retrieval can be primarily attributed to the association between foliar nutrients and other leaf components (e.g., pigments, water, and dry matter) that do display spectral features within this range. Our study demonstrated the potential of integrating multi-source satellite data for precise nutrient monitoring over large scales.

BackgroundAttention Deficit Hyperactivity Disorder (ADHD) frequently persists into adulthood. There are practice guidelines that outline the requirements for the assessment and treatment of adults. Nevertheless, guidelines specifying what constitutes a good quality diagnostic assessment and report and the competencies required to be a specialist assessor are lacking. This can lead to variation in the quality and reliability of adult ADHD assessments. Poor quality assessments may not be accepted as valid indicators of the presence of ADHD by other clinicians or services, resulting in wasteful re-assessments and delays in providing treatment. To address this issue the UK Adult ADHD Network (UKAAN) proposes a quality framework for adult ADHD assessments - the Adult ADHD Assessment Quality Assurance Standard (AQAS).MethodsThe co-authors agreed on five questions or themes that then guided the development of a set of consensus statements. An initial draft was reviewed and amended in an iterative process to reach a final consensus.ResultsWhat constitutes a high-quality diagnostic assessment and report was agreed by consensus of the co-authors. The resulting guideline emphasises the need to evaluate impairment, describes core competencies required by the assessor and highlights the importance of linking the diagnosis to an appropriate post-diagnostic discussion. Assessments should be completed in the context of a full psychiatric and neurodevelopmental review, and need good interview skills, using a semi-structured interview with open questioning and probing to elicit real life examples of symptoms and impairments. It is recommended that 2 hours or more is required for an adequate assessment including both the diagnostic assessment and initial post-assessment discussions.ConclusionThe AQAS has been developed as a practical resource to support reliable and valid diagnostic assessments of adult ADHD. It is intended to complement formal training. A secondary objective is to empower patients by providing them with evidence-based information on what to expect from an assessment and assessment report.

Abstract Switchgrass (Panicum virgatum L.) is a prominent bioenergy crop with robust resilience to environmental stresses. However, our knowledge regarding how precipitation changes affect switchgrass photosynthesis and its responses to light and CO2 remains limited. To address this knowledge gap, we conducted a field precipitation experiment with five different treatments, including −50%, −33%, 0%, +33%, and +50% of ambient precipitation. To determine the responses of leaf photosynthesis to CO2 concentration and light, we measured leaf net photosynthesis of switchgrass under different CO2 concentrations and light levels in 2020 and 2021 for each of the five precipitation treatments. We first evaluated four light and CO2 response models (i.e., rectangular hyperbola model, nonrectangular hyperbola model, exponential model, and the modified rectangular hyperbola model) using the measurements in the ambient precipitation treatment. Based on the fitting criteria, we selected the nonrectangular hyperbola model as the optimal model and applied it to all precipitation treatments, and estimated model parameters. Overall, the model fit field measurements well for the light and CO2 response curves. Precipitation change did not influence the maximum net photosynthetic rate (Pmax) but influenced other model parameters including quantum yield (α), convexity (θ), dark respiration (Rd), light compensation point (LCP), and saturated light point (LSP). Specifically, the mean Pmax of five precipitation treatments was 17.6 μmol CO2 m−2 s−1, and the ambient treatment tended to have a higher Pmax. The +33% treatment had the highest α, and the ambient treatment had lower θ and LCP, higher Rd, and relatively lower LSP. Furthermore, precipitation significantly influenced all model parameters of CO2 response. The ambient treatment had the highest Pmax, largest α, and lowest θ, Rd, and CO2 compensation point LCP. Overall, this study improved our understanding of how switchgrass leaf photosynthesis responds to diverse environmental factors, providing valuable insights for accurately modeling switchgrass ecophysiology and productivity.

Metabolomics is a critical approach to fully understand the metabolic repercussions of a nutritional supplement on the gut microbiota. Here, a proof of principle study was conducted via a metabolomic survey of polar metabolites to explore the effect of AG1 on the metabolic output of the human gut microbiota, in vitro, using the Simulator of the Human Intestinal Microbial Ecosystem® (SHIME). Aliquots were isolated from the fecal slurry at baseline (0 h), 1 h, 24 h, and 48 h of colonic fermentation simulation. Chemical analysis at these timepoints detected a total of 165 metabolites with 57, 21, and 14 specific metabolites being significantly altered by AG1 relative to the blank controls at 1 h, 24 h, and 48 h, respectively. Many of these metabolites likely resulted from AG1 directly as a supplement, but several of these metabolites also likely arose specifically from microbial metabolism.

Research has shown that food insecurity in households and communities are increasing globally. More people are reported to now having difficulty in accessing safe and quality foods. This study assessed household food and water access as predictors of food security among rural households. This is a cross sectional community survey which used validated tools to collect data among 201 households representing a total population of 1284 in Langai district. Levels of household food and water access were determined; and factors associated with food security were assessed using chi-square. Predictors of food security was assessed using multivariable logistic regression. P < 0,05 was adjudged significant. About 90 % of households own a farm; with almost two-thirds (62,2 %) of households acquiring their food from both self-production and market; and 73,6 % engaging in household agriculture. The majority (82,1 %) of the households sourced their water from boreholes and pipe-borne sources. Significant predictors of food security were lower expenditure on food (AOR: 2,19 [95 % CI: 1,5-4,61]; P = 0,038); not engaged in household agriculture (AOR: 2,88 [95 % CI: 1,09-7,59]; P = 0,032); had access to pipe borne/borehole water (AOR: 2,76 [95 % CI: 1,15-6,44]; P = 0,023) and experienced little or no adverse coping behaviour (AOR: 6,07 [95 % CI: 1,74-21,23]; P = 0,005). Time did not influence food acquisition in the majority of the households. As reported and showcased in this study, the relationship between food security and rural household development is directly proportional in many local communities of a developing country. Efforts should be garnered towards rural household empowerment through improvement in livelihood and security to have sustainable foods and water.

The brittle fracture pattern in plastics associated with low toughness performance have a negative effect on their performance especially for long-term and specialized applications. This review provides a comprehensive understanding of toughening mechanisms in polyethylene (PE) and the details of different techniques for achieving a balance between strength and toughness in PE-based composites. Various strategies for toughening, along with the parameters involved in processing and materials development, such as matrix chemical modification, use of a second phase, and incorporation of coupling agents are discussed in detail. Current challenges and future opportunities for simultaneous toughening and strengthening in PE-based composites are outlined for further research and development in academia and industry to expand the applications of PE composites, overcome current challenges, and provide useful insights for further advancements, particularly in the area of toughened composites.

Abstract UK Biobank is a large-scale epidemiological resource for investigating prospective correlations between various lifestyle, environmental, and genetic factors with health and disease progression. In addition to individual subject information obtained through surveys and physical examinations, a comprehensive neuroimaging battery consisting of multiple modalities provides imaging-derived phenotypes (IDPs) that can serve as biomarkers in neuroscience research. In this study, we augment the existing set of UK Biobank neuroimaging structural IDPs, obtained from well-established software libraries such as FSL and FreeSurfer, with related measurements acquired through the Advanced Normalization Tools Ecosystem. This includes previously established cortical and subcortical measurements defined, in part, based on the Desikan-Killiany-Tourville atlas. Also included are morphological measurements from two recent developments: medial temporal lobe parcellation of hippocampal and extra-hippocampal regions in addition to cerebellum parcellation and thickness based on the Schmahmann anatomical labeling. Through predictive modeling, we assess the clinical utility of these IDP measurements, individually and in combination, using commonly studied phenotypic correlates including age, fluid intelligence, numeric memory, and several other sociodemographic variables. The predictive accuracy of these IDP-based models, in terms of root-mean-squared-error or area-under-the-curve for continuous and categorical variables, respectively, provides comparative insights between software libraries as well as potential clinical interpretability. Results demonstrate varied performance between package-based IDP sets and their combination, emphasizing the need for careful consideration in their selection and utilization.

Abstract Van Hove singularities (VHss) in the vicinity of the Fermi energy often play a dramatic role in the physics of strongly correlated electron materials. The divergence of the density of states generated by VHss can trigger the emergence of phases such as superconductivity, ferromagnetism, metamagnetism, and density wave orders. A detailed understanding of the electronic structure of these VHss is therefore essential for an accurate description of such instabilities. Here, we study the low-energy electronic structure of the trilayer strontium ruthenate Sr4Ru3O10, identifying a rich hierarchy of VHss using angle-resolved photoemission spectroscopy and millikelvin scanning tunneling microscopy. Comparison of k-resolved electron spectroscopy and quasiparticle interference allows us to determine the structure of the VHss and demonstrate the crucial role of spin-orbit coupling in shaping them. We use this to develop a minimal model from which we identify a mechanism for driving a field-induced Lifshitz transition in ferromagnetic metals.

Abstract Background Current automated planning solutions are calibrated using trial and error or machine learning on historical datasets. Neither method allows for the intuitive exploration of differing trade-off options during calibration, which may aid in ensuring automated solutions align with clinical preference. Pareto navigation provides this functionality and offers a potential calibration alternative. The purpose of this study was to validate an automated radiotherapy planning solution with a novel multi-dimensional Pareto navigation calibration interface across two external institutions for prostate cancer. Methods The implemented ‘Pareto Guided Automated Planning’ (PGAP) methodology was developed in RayStation using scripting and consisted of a Pareto navigation calibration interface built upon a ‘Protocol Based Automatic Iterative Optimisation’ planning framework. 30 previous patients were randomly selected by each institution (IA and IB), 10 for calibration and 20 for validation. Utilising the Pareto navigation interface automated protocols were calibrated to the institutions’ clinical preferences. A single automated plan (VMATAuto) was generated for each validation patient with plan quality compared against the previously treated clinical plan (VMATClinical) both quantitatively, using a range of DVH metrics, and qualitatively through blind review at the external institution. Results PGAP led to marked improvements across the majority of rectal dose metrics, with Dmean reduced by 3.7 Gy and 1.8 Gy for IA and IB respectively (p

Underwater construction, maintenance, and mapping use autonomous underwater vehicles (AUVs) for path planning, path following, and target tracking operations. However, dynamic position management and localization of AUVs are critical issues. Correct localization and dynamic position management to prevent drifts can be used to acquire information on energy efficiency, another crucial topic. In this paper, AUV dynamic modeling using experimental data and position control is studied. The experiments were implemented on a Delphin2 scaled AUV model belonging to the Engineering and Environment Faculty, University of Southampton, UK. Hover and flight style motions according to the different speeds of Delphin2 were implemented in the test tank. Nonlinear coupled mathematical models were studied using shallow neural networks. The models are formed into depth-pitch and heading motion black-box models using the shallow neural network (SNN) algorithm. Proportional integral derivative control of heading motions and depth-pitch motion simulation studies were applied to the SNN model.

Abstract Chronic kidney diseases (CKD) have genetic associations with kidney function. Univariate genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with estimated glomerular filtration rate (eGFR) and blood urea nitrogen (BUN), two complementary kidney function markers. However, it is unknown whether additional SNPs for kidney function can be identified by multivariate statistical analysis. To address this, we applied canonical correlation analysis (CCA), a multivariate method, to two individual-level CKD genotype datasets, and metaCCA to two published GWAS summary statistics datasets. We identified SNPs previously associated with kidney function by published univariate GWASs with high replication rates, validating the metaCCA method. We then extended discovery and identified previously unreported lead SNPs for both kidney function markers, jointly. These showed expression quantitative trait loci (eQTL) colocalisation with genes having significant differential expression between CKD and healthy individuals. Several of these identified lead missense SNPs were predicted to have a functional impact, including in SLC14A2. We also identified previously unreported lead SNPs that showed significant correlation with both kidney function markers, jointly, in the European ancestry CKDGen, National Unified Renal Translational Research Enterprise (NURTuRE)-CKD and Salford Kidney Study (SKS) datasets. Of these, rs3094060 colocalised with FLOT1 gene expression and was significantly more common in CKD cases in both NURTURE-CKD and SKS, than in the general population. Overall, by using multivariate analysis by CCA, we identified additional SNPs and genes for both kidney function and CKD, that can be prioritised for further CKD analyses.

Abstract Development of high yielding cowpea varieties coupled with good taste and rich in essential minerals can promote consumption and thus nutrition and profitability. The sweet taste of cowpea grain is determined by its sugar content, which comprises mainly sucrose and galacto-oligosaccharides (GOS) including raffinose and stachyose. However, GOS are indigestible and their fermentation in the colon can produce excess intestinal gas, causing undesirable bloating and flatulence. In this study, we aimed to examine variation in grain sugar and mineral concentrations, then map quantitative trait loci (QTLs) and estimate genomic-prediction (GP) accuracies for possible application in breeding. Grain samples were collected from a multi-parent advanced generation intercross (MAGIC) population grown in California during 2016–2017. Grain sugars were assayed using high-performance liquid chromatography. Grain minerals were determined by inductively coupled plasma–optical emission spectrometry and combustion. Considerable variation was observed for sucrose (0.6–6.9%) and stachyose (2.3–8.4%). Major QTLs for sucrose (QSuc.vu-1.1), stachyose (QSta.vu-7.1), copper (QCu.vu-1.1) and manganese (QMn.vu-5.1) were identified. Allelic effects of major sugar QTLs were validated using the MAGIC grain samples grown in West Africa in 2017. GP accuracies for minerals were moderate (0.4–0.58). These findings help guide future breeding efforts to develop mineral-rich cowpea varieties with desirable sugar content.

Abstract Sleep disturbance is a prevalent and disabling comorbidity in Parkinson’s disease (PD). We performed multi-night (n = 57) at-home intracranial recordings from electrocorticography and subcortical electrodes using sensing-enabled Deep Brain Stimulation (DBS), paired with portable polysomnography in four PD participants and one with cervical dystonia (clinical trial: NCT03582891). Cortico-basal activity in delta increased and in beta decreased during NREM (N2 + N3) versus wakefulness in PD. DBS caused further elevation in cortical delta and decrease in alpha and low-beta compared to DBS OFF state. Our primary outcome demonstrated an inverse interaction between subcortical beta and cortical slow-wave during NREM. Our secondary outcome revealed subcortical beta increases prior to spontaneous awakenings in PD. We classified NREM vs. wakefulness with high accuracy in both traditional (30 s: 92.6 ± 1.7%) and rapid (5 s: 88.3 ± 2.1%) data epochs of intracranial signals. Our findings elucidate sleep neurophysiology and impacts of DBS on sleep in PD informing adaptive DBS for sleep dysfunction.

Abstract Background Persons with opioid use disorders who inject drugs (PWID) in the United States (US) face multiple and intertwining health risks. These include interference with consistent access, linkage, and retention to health care including medication for opioid use disorder (MOUD), HIV prevention using pre-exposure prophylaxis (PrEP), and testing and treatment for sexually transmitted infections (STIs). Most services, when available, including those that address substance misuse, HIV prevention, and STIs, are often provided in multiple locations that may be difficult to access, which further challenges sustained health for PWID. HPTN 094 (INTEGRA) is a study designed to test the efficacy of an integrated, “whole-person” strategy that provides integrated HIV prevention including antiretroviral therapy (ART), PrEP, MOUD, and STI testing and treatment from a mobile health delivery unit (“mobile unit”) with peer navigation compared to peer navigation alone to access these services at brick and mortar locations. Methods HPTN 094 (INTEGRA) is a two-arm, randomized controlled trial in 5 US cities where approximately 400 PWID without HIV are assigned either to an experimental condition that delivers 26 weeks of “one-stop” integrated health services combined with peer navigation and delivered in a mobile unit or to an active control condition using peer navigation only for 26 weeks to the same set of services delivered in community settings. The primary outcomes include being alive and retained in MOUD and PrEP at 26 weeks post-randomization. Secondary outcomes measure the durability of intervention effects at 52 weeks following randomization. Discussion This trial responds to a need for evidence on using a “whole-person” strategy for delivering integrated HIV prevention and substance use treatment, while testing the use of a mobile unit that meets out-of-treatment PWID wherever they might be and links them to care systems and/or harm reduction services. Findings will be important in guiding policy for engaging PWID in HIV prevention or care, substance use treatment, and STI testing and treatment by addressing the intertwined epidemics of addiction and HIV among those who have many physical and geographic barriers to access care. Trial registration ClinicalTrials.gov NCT04804072 . Registered on 18 March 2021.

Abstract Background Globally, close to one-third of all workplace violence (WV) occurs in the health sector. Exposure to WV among healthcare professionals in Ghana has been widely speculated, but there is limited evidence on the problem. This study therefore investigated WV, its risk factors, and the psychological consequences experienced by health workers in Ghana. Methods An analytic cross-sectional study was conducted in the Greater Accra region from January 30 to May 31, 2023, involving selected health facilities. The participants for the study were selected using a simple random sampling technique based on probability proportional-to-size. The data analyses were performed using STATA 15 software. Logistic regression analyses were employed to identify the factors associated with WV, considering a significance level of p-value

Abstract Background Male sex workers (MSWs), specifically cisgender men who exchange sex for money, goods, drugs, or other items of value with other cisgender men, are at high risk for HIV infection. Compared to men not engaged in sex work, MSWs are more likely to engage in frequent condomless sex with paying and non-paying sexual partners. While MSWs are often included as a subgroup of gay and bisexual men, data show that a large proportion identify as heterosexual; additionally, most MSWs do not identify as “sex workers.” This places MSWs in a unique position where they may not engage with traditional HIV prevention programs, and when they do, they may not feel comfortable, leading to poor retention. Thus, HIV prevention interventions that address MSWs’ unique life circumstances and provide support in exploring their sexual health options are needed. Methods In this protocol paper, we describe the design and procedures for a National Institute of Health-funded, randomized controlled trial testing the efficacy of “PrEPare for Work,”— a theory-based, manualized PrEP uptake and adherence intervention for MSW — using a 2-stage randomization design. Stage 1: MSWs are equally randomized to receive either the “PrEPare for Work Stage 1 intervention” (strength-based case management and facilitated PrEP linkage) or Standard of Care (SOC) to evaluate successful PrEP uptake (prescription filled) within two months post-randomization. Stage 2: Those who initiate PrEP are then equally re-randomized to receive either the “PrEPare for Work Stage 2 intervention” (1-on-1 skills training, problem-solving, and motivational interviewing adherence counseling and personalized, daily text message reminders) or SOC to assess adherence (Tenofovir concentrations in hair) over 12 months of follow up. Planned analyses will examine intervention efficacy, specific conceptual mediators, and hypothesized moderators. Discussion Based on our extensive preliminary research, multi-component, theory-informed interventions targeting this subpopulation of MSWs’ unique life circumstances are urgently needed. In this study, we are evaluating whether “PrEPare for Work” can improve PrEP uptake and adherence among MSWs. If this intervention is efficacious, it would be readily disseminated to diverse community organizations that serve MSWs and possibly other community or clinic-based settings. Trial registration ClinicalTrials.gov number NCT05736614, registered February 8, 2023.

Objective: In patients undergoing elective thoracic surgery, frailty is associated with worse outcomes. However, the magnitude by which frailty influences outcomes of urgent thoracic surgery (UTS) is unknown. Methods: We identified patients admitted with a UTS condition from January to September 2017 in the National Readmissions Database. UTS conditions were classified as esophageal perforation, hemo/pneumothorax, rib fracture, and obstructed hiatal hernia. Outcome of interest was mortality within 90 days of index admission. Frailty score was calculated using a deficit accumulation method. Cox proportional hazard modeling was used to calculate a hazard ratio for each combination of UTS disease type and frailty score, adjusted for sex, insurance payor, hospital size, and hospital and patient location, and was compared with the effect of frailty on elective lung lobectomy. Results: We identified 107,487 patients with a UTS condition. Among UTS conditions overall, increasing frailty elements were associated with increased mortality (hazard ratio, 2270; 95% CI, 1463-3523; P

Objectives: Chronic diarrhoea and severe wasting associated with HIV infection were first described in East African patients as slim disease (SD) in 1985. The main histological features are flattening of the villi (villous atrophy) and crypt hyperplasia (elongated crypts), i.e., HIV enteropathy (HIVE). Selective loss of mucosal clusters of differentiation 4 (CD4)+ T helper (Th)17+ lymphocytes is the immunological hallmark of HIVE. This review explores (i) the historical background of HIVE and SD, (ii) the relationship between gut mucosal CD4+ Th17+ and intestinal-resident intra-epithelial gamma delta (IRIE) T lymphocytes in pathogenesis of HIVE, (iii) the role of cytokines in regulation of intestinal epithelial proliferation, and (iv) the role of antiretroviral therapy in HIVE. Methods: Recent studies have highlighted the role of IRIE T lymphocytes, mostly CD8+, in regulating gut epithelial regeneration. CD4+Th17+ and IRIE T cells are necessary to maintain intestinal barrier integrity and mucosal antimicrobial immune defence. However, the immunological cross-talk between such lymphocyte sub-sets culminating in HIVE is uncertain. We undertook a narrative literature review under the headings ‘HIVE’, ‘SD’, and 'Highly active antiretroviral therapy (HAART). Relevant studies were located using the electronic search engines Google Scholar and PubMed from 1984 to 2022. Results: Depletion of Th17+ cells in the lamina propria, attributed to low-level viraemia, is accompanied by concomitant increase in the density of gut mucosal IRIE T lymphocytes in AIDS. The latter express a broad range of cytokines (interferon-gamma, tumor necrosis factor-alpha, interleukin-17) and chemokines e.g., keratinocyte growth factor, post exposure to HIV-infected cells. Keratinocyte growth factor induces epithelial proliferation mainly in the crypts, leading to functional immaturity of enterocytes, reduced gut absorptive surface area and malabsorption in animal experiments. Of note, the absence of IRIE T cells is associated with a reduction in epithelial cell turnover. Patients with HIVE receiving early HAART show enhanced expression of mucosal repair genes and improvement of gut symptoms. Conclusion: Multiple lines of enquiry suggest HIVE is directly related to HIV infection and is a consequence of perturbations in mucosal CD4+Th17+ and IRIE T lymphocytes. The pathological result is enterocyte immaturity and dysfunction. SD whose main features are malabsorption, diarrhoea and weight loss, is a severe clinical expression of HIVE. A better understanding of immuno-pathogenesis of HIVE opens a window of opportunity for the potential use of immunotherapy in HIV disease and other T cell-mediated enteropathies.

Background In Tanzania, nearly half of ever-married women have experienced some form of intimate partner violence (IPV), yet little knowledge of IPV from the male perspective exists. Objective To explore the role of essential healthy lifestyle factors, diet, sleep, and exercise, and their potential role in IPV perpetration. Methods A cross-sectional survey was conducted with 1,002 young men (ages 18–24), 754 of which were in an intimate relationship in the previous year. The study took place in Mwanza, Tanzania and used multivariable logistic regression models to explore associations between male perpetration of IPV and diet, sleep, and exercise. Results Six types of IPV perpetration were investigated separately and the prevalence of controlling behaviours (79.4%), economic abuse (30.6%), emotional abuse (47.3%), physical violence (16.4%), sexual violence (23.3%), and combined physical and/or sexual violence (32.1%) were obtained. Regular exercise demonstrated a protective effect for economic abuse perpetration; the chance of mildly active individuals perpetrating economic abuse was 38% less than their inactive counterparts (p = 0.003). Associations with sleep were varied and did not show a clear directional relationship. Diet, defined as poor food variety, was positively associated with every IPV type except physical violence and was significant in sexual violence perpetration (aOR:1.57, 95%CI:1.21–2.05). Conclusions The results from this study indicate that considering healthy lifestyle behaviours – diet, sleep, and exercise – in the design of intervention programmes may be beneficial in reducing IPV perpetration in Tanzania, and that they should be considered alongside previously established evidence-based risk factors.

Since Ghana gained independence in 1957, successive governments have implemented various development interventions aimed at poverty alleviation. Yet, the dilemma of uneven development persists amongst rural and urban areas and between Northern and Southern Ghana. The implications of these growing disparities are far-reaching. A myriad of migration streams from Northern to Southern Ghana aimed at better lives have been chronicled since pre-colonial era. However, very few empirical studies have tried to examine the impact of migration on overall wellbeing of migrants. This paper used cross-sectional survey data gathered through a structured questionnaire and key informant interviews to assess the contribution of internal migration on human wellbeing. The findings reveal that the proportion of migrants who were food secured increased from 8.3% (before migration) to 34.4% (after migration). The results further indicate that there is a statistically significant increase in the average income, expenditure, and savings of migrants after migration; and there is a statistically significant increase in the number of migrants who own houses after migration. The findings are an indication that internal migration in Ghana has had a positive impact on the health, economic and social conditions of migrants. The study acknowledges that the well-being of migrants extends beyond these factors and calls for further research to investigate the impact of migration on other aspects of wellbeing such as psychological well-being.