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Abstract The bacterial genus Salmonella includes diverse isolates with multiple variations in the structure of the main polysaccharide component (O antigen) of membrane lipopolysaccharides. In addition, some isolates produce a transient (T) antigen, such as the T1 polysaccharide identified in the 1960s in an isolate of Salmonella enterica Paratyphi B. The structure and biosynthesis of the T1 antigen have remained enigmatic. Here, we use biophysical, biochemical and genetic methods to show that the T1 antigen is a complex linear glycan containing tandem homopolymeric domains of galactofuranose and ribofuranose, linked to lipid A–core, like a typical O antigen. T1 is a phase-variable antigen, regulated by recombinational inversion of the promoter upstream of the T1 genetic locus through a mechanism not observed for other bacterial O antigens. The T1 locus is conserved across many Salmonella isolates, but is mutated or absent in most typhoidal serovars and in serovar Enteritidis.

Abstract Therapeutic approaches targeting proteins on the surface of cancer cells have emerged as an important strategy for precision oncology. To capitalize on the potential impact of drugs targeting surface proteins, detailed knowledge about the expression patterns of the target proteins in tumor tissues is required. In castration-resistant prostate cancer (CRPC), agents targeting prostate-specific membrane antigen (PSMA) have demonstrated clinical activity. However, PSMA expression is lost in a significant number of CRPC tumors. The identification of additional cell surface targets is necessary to develop new therapeutic approaches. Here, we performed a comprehensive analysis of the expression heterogeneity and co-expression patterns of trophoblast cell-surface antigen 2 (TROP2), delta-like ligand 3 (DLL3), and carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) in CRPC samples from a rapid autopsy cohort. We show that DLL3 and CEACAM5 exhibit the highest expression in neuroendocrine prostate cancer (NEPC), while TROP2 is expressed across different CRPC molecular subtypes, except for NEPC. We further demonstrated that AR alterations were associated with higher expression of PSMA and TROP2. Conversely, PSMA and TROP2 expression was lower in RB1-altered tumors. In addition to genomic alterations, we show a tight correlation between epigenetic states, particularly histone H3 lysine 27 methylation (H3K27me3) at the transcriptional start site and gene body of TACSTD2 (encoding TROP2), DLL3, and CEACAM5, and their respective protein expression in CRPC patient-derived xenografts. Collectively, these findings provide insights into patterns and determinants of expression of TROP2, DLL3, and CEACAM5 with implications for the clinical development of cell surface targeting agents in CRPC.

Abstract Distinguishing indolent from clinically significant localized prostate cancer is a major clinical challenge and influences clinical decision-making between treatment and active surveillance. The development of novel predictive biomarkers will help with risk stratification, and clinical decision-making, leading to a decrease in over or under-treatment of patients with prostate cancer. Here, we report that Trop2 is a prognostic tissue biomarker for clinically significant prostate cancer by utilizing the Canary Prostate Cancer Tissue Microarray (CPCTA) cohort composed of over 1100 patients from a multi-institutional study. We demonstrate that elevated Trop2 expression is correlated with worse clinical features including Gleason score, age, and pre-operative PSA levels. More importantly, we demonstrate that elevated Trop2 expression at radical prostatectomy predicts worse overall survival in men undergoing radical prostatectomy. Additionally, we detect shed Trop2 in urine from men with clinically significant prostate cancer. Our study identifies Trop2 as a novel tissue prognostic biomarker and a candidate non-invasive marker for prostate cancer.

Background: Several studies have linked coronavirus disease 2019 (COVID-19) risk to age and ABO blood groups. Variations in plasma angiotensin-converting enzyme 2 (ACE2) levels and blood counts have been reported, suggesting an association between disease severity and low lymphocyte levels. Aim: this study aimed to understand how these factors relate to COVID-19 in Ghanaian patients, considering geographical and demographic differences. Methods: Participants were recruited from six hospitals in Kumasi, Ghana, between June 2020 and July 2021. Nasopharyngeal swabs were taken to test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and blood samples were collected for complete blood count testing, ABO/Rhesus typing, and assessment of plasma ACE2 levels. Demographic and COVID-19 severity data were gathered, and IBM SPSS version 25.0 was used for analysis. Results: Overall, 515 patients were enrolled, out of which 55.9% (n = 288/515) were males and 50.3% (n = 259/515) tested positive for SARS-CoV-2. The median age was 37 years (IQR = 26–53). Age was significantly associated with SARS-CoV-2 infection (p = 0.002). The severe COVID-19 group was the oldest (70 years, IQR = 35–80) and presented with anaemia (haemoglobin, g/dL: 9.55, IQR = 7.85–11.93), leukocytosis (WBC × 103/μL: 15.87, IQR = 6.68–19.80), neutrophilia (NEUT × 106/μL: 14.69, IQR = 5.70–18.96) and lymphocytopenia (LYMPH × 106/μL: 0.47, IQR = 0.22–0.66). No association was found between SARS-CoV-2 positivity and ABO (p = 0.711) or Rh (p = 0.805) blood groups; no association was also found between plasma ACE2 levels and SARS-CoV-2 status (p = 0.079). However, among COVID-19 participants, plasma ACE2 levels were significantly reduced in the moderate illness group (40.68 ng/mL, IQR = 34.09–48.10) compared with the asymptomatic group (50.61 ng/mL, IQR = 43.90–58.61, p = 0.015). Conclusions: While there may be no real association between the ABO blood group, as well as plasma ACE2 levels, and SARS-CoV-2 infection in Ghanaian patients, older individuals are at a higher risk of severe disease. Anaemia, and leukocytosis with lymphocytopenia may be indicators of poor disease progression.

Prolactinomas are the most common pituitary tumors and are treated with surgery with or without dopamine agonists. Amyloid in prolactinoma is known to occur, but spherical type of amyloid deposition is extremely rare and can pose a diagnostic challenge during intraoperative consultation. They do not respond to medical treatment with dopamine agonists and enlarge in size or undergo fibrosis, causing a failure of medical therapy. Hence, it needs to be identified preoperatively by imaging to institute appropriate management. Here we report a case of a 50 year male with symptoms of burning sensations in the left upper limb and temporal seizures for 4 months. Magnetic resonance imaging showed a well-defined lobulated lesion measuring 4x3.5x3cm eroding the floor of sella. Histology showed spherical, eosinophilic amyloid material with focal cellular areas. Immunohistochemistry and serum levels were high for prolactin. 11 months later, the patient was readmitted with CSF rhinorrhea. The biopsy revealed abundant spherical amyloid with scant cellularity suggesting a recurrence.

Abstract Advancing personalized medicine in brain cancer relies on innovative strategies, with mRNA vaccines emerging as a promising avenue. While the initial use of mRNA vaccines was in oncology, their stunning success in COVID-19 resulted in widespread attention, both positive and negative. Regardless of politically biased opinions, which relate more to the antigenic source than form of delivery, we feel it is important to objectively review this modality as relates to brain cancer. This class of vaccines trigger robust immune responses through MHC-I and MHC-II pathways, in both prophylactic and therapeutic settings. The mRNA platform offers advantages of rapid development, high potency, cost-effectiveness, and safety. This review provides an overview of mRNA vaccine delivery technologies, tumor antigen identification, combination therapies, and recent therapeutic outcomes, with a particular focus on brain cancer. Combinatorial approaches are vital to maximizing mRNA cancer vaccine efficacy, with ongoing clinical trials exploring combinations with adjuvants and checkpoint inhibitors and even adoptive cell therapy. Efficient delivery, neoantigen identification, preclinical studies, and clinical trial results are highlighted, underscoring mRNA vaccines' potential in advancing personalized medicine for brain cancer. Synergistic combinatorial therapies play a crucial role, emphasizing the need for continued research and collaboration in this area.

Abstract Background Controversy over treatment for people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a barrier to appropriate treatment. Energy management or pacing is a prominent coping strategy for people with ME/CFS. Whilst a definitive definition of pacing is not unanimous within the literature or healthcare providers, it typically comprises regulating activity to avoid post exertional malaise (PEM), the worsening of symptoms after an activity. Until now, characteristics of pacing, and the effects on patients’ symptoms had not been systematically reviewed. This is problematic as the most common approach to pacing, pacing prescription, and the pooled efficacy of pacing was unknown. Collating evidence may help advise those suffering with similar symptoms, including long COVID, as practitioners would be better informed on methodological approaches to adopt, pacing implementation, and expected outcomes. Objectives In this scoping review of the literature, we aggregated type of, and outcomes of, pacing in people with ME/CFS. Eligibility criteria Original investigations concerning pacing were considered in participants with ME/CFS. Sources of evidence Six electronic databases (PubMed, Scholar, ScienceDirect, Scopus, Web of Science and the Cochrane Central Register of Controlled Trials [CENTRAL]) were searched; and websites MEPedia, Action for ME, and ME Action were also searched for grey literature, to fully capture patient surveys not published in academic journals. Methods A scoping review was conducted. Review selection and characterisation was performed by two independent reviewers using pretested forms. Results Authors reviewed 177 titles and abstracts, resulting in 17 included studies: three randomised control trials (RCTs); one uncontrolled trial; one interventional case series; one retrospective observational study; two prospective observational studies; four cross-sectional observational studies; and five cross-sectional analytical studies. Studies included variable designs, durations, and outcome measures. In terms of pacing administration, studies used educational sessions and diaries for activity monitoring. Eleven studies reported benefits of pacing, four studies reported no effect, and two studies reported a detrimental effect in comparison to the control group. Conclusions Highly variable study designs and outcome measures, allied to poor to fair methodological quality resulted in heterogenous findings and highlights the requirement for more research examining pacing. Looking to the long COVID pandemic, our results suggest future studies should be RCTs utilising objectively quantified digitised pacing, over a longer duration of examination (i.e. longitudinal studies), using the core outcome set for patient reported outcome measures. Until these are completed, the literature base is insufficient to inform treatment practises for people with ME/CFS and long COVID.

BackgroundWith the rise of smartphone ownership and increasing evidence to support the suitability of smartphone usage in healthcare, the light source and smartphone camera could be utilized to perform photoplethysmography (PPG) for the assessment of vital signs, such as heart rate (HR). However, until rigorous validity assessment has been conducted, PPG will have limited use in clinical settings.ObjectiveWe aimed to conduct a scoping review assessing the validity of resting heart rate (RHR) acquisition from PPG utilizing contact-based smartphone devices. Our four specific objectives of this scoping review were to (1) conduct a systematic search of the published literature concerning contact-based smartphone device-derived PPG, (2) map study characteristics and methodologies, (3) identify if methodological and technological advancements have been made, and (4) provide recommendations for the advancement of the investigative area.MethodsScienceDirect, PubMed and SPORTDiscus were searched for relevant studies between January 1st, 2007, and November 6th, 2022. Filters were applied to ensure only literature written in English were included. Reference lists of included studies were manually searched for additional eligible studies.ResultsIn total 10 articles were included. Articles varied in terms of methodology including study characteristics, index measurement characteristics, criterion measurement characteristics, and experimental procedure. Additionally, there were variations in reporting details including primary outcome measure and measure of validity. However, all studies reached the same conclusion, with agreement ranging between good to very strong and correlations ranging from r = .98 to 1.ConclusionsSmartphone applications measuring RHR derived from contact-based smartphone PPG appear to agree with gold standard electrocardiography (ECG) in healthy subjects. However, agreement was established under highly controlled conditions. Future research could investigate their validity and consider effective approaches that transfer these methods from laboratory conditions into the “real-world”, in both healthy and clinical populations.

Background: Telazorlimab is a humanized anti-OX40 monoclonal antibody being studied for treatment of T-cell–mediated diseases. Objective: This randomized, placebo-controlled, phase 2b dose-range finding study investigated efficacy, safety, pharmacokinetics, and immunogenicity of telazorlimab in subjects with atopic dermatitis. Methods: In this 2-part study (NCT03568162), adults (≥18 years) with moderate-to-severe disease were randomized to various regimens of subcutaneous telazorlimab or placebo for 16 weeks’ blinded treatment, followed by 38 weeks’ open-label treatment and 12 weeks’ drug-free follow-up. Telazorlimab treatment groups (following a loading dose) in part 1 were 300 mg every 2 weeks; 300 mg every 4 weeks; or 75 mg every 4 weeks. Part 2 evaluated telazorlimab 600 mg every 2 weeks. The primary end point was percentage change from baseline in Eczema Area and Severity Index (EASI) at week 16. Safety assessments included incidence of treatment-emergent adverse events. Results: The study randomized 313 subjects in part 1 and 149 in part 2. At 16 weeks, the least squares mean percentage change from baseline in EASI was significantly greater in subjects receiving telazorlimab 300 mg every 2 weeks (part 1) and 600 mg every 2 weeks (part 2) versus placebo (−54.4% vs −34.2% for part 1 and −59.0% vs −41.8% for part 2, P = .008 for both). Telazorlimab was well tolerated, with similar distribution of adverse events between telazorlimab- and placebo-treated subjects in both part 1 and part 2. Conclusion: Telazorlimab, administered subcutaneously at 300 mg every 2 weeks or 600 mg every 2 weeks following a loading dose, was well tolerated and induced significant and progressive clinical improvement in adults with moderate-to-severe atopic dermatitis.

This investigation explored relationships between biological maturation, physical and academic performance in young male soccer players. Thirty-eight players (age: 9.79 ± 1.21 years; body mass index (BMI): 20.4 ± 2.39 kg/m2; body fat: 16.8 ± 2.21%) participated. Measures of anthropometry used for body mass, body fat percentage (%BF), and BMI as well. Postural control, 15 m sprint, squat jumps and counter-movement jumps (SJ, CMJ), and T-half test for change-of-direction (CoD) were parameters of physical performance. The grade point average (GPA) of mathematics determined academic attainment. Moore's equations were used to estimate their maturity status (PHV). Biological maturation was highly correlated with most (not 15 m sprint) physical and academic performance parameters, especially CMJ (r = -0.812) and mathematics (r = -0.781). Academic performance showed the largest relations to the jumping performance (CMJ: r = 0.771; SJ: r = 0.723). In contrast, anthropometric and fatness parameters were not relevantly (r ≥ 0.5) correlated with any other parameters. The largest correlations were calculated for sitting height vs. SJ (r = -0.408), sitting height vs. postural control (r = -0.355), leg length vs. postural control (r = -0.339). As a result, it is essential to take biological maturation inconsideration while assessing the physical and academic achievement of young soccer players. In consequence, soccer coaches and physical education (PE) teachers should be cognizant of the impact of biological maturity on physical and academic performance to assist fair and equal opportunities for achievement in young players.

Abstract In recent years, technological advances in tissue preparation, high‐throughput volumetric microscopy, and computational infrastructure have enabled rapid developments in nondestructive 3D pathology, in which high‐resolution histologic datasets are obtained from thick tissue specimens, such as whole biopsies, without the need for physical sectioning onto glass slides. While 3D pathology generates massive datasets that are attractive for automated computational analysis, there is also a desire to use 3D pathology to improve the visual assessment of tissue histology. In this perspective, we discuss and provide examples of potential advantages of 3D pathology for the visual assessment of clinical specimens and the challenges of dealing with large 3D datasets (of individual or multiple specimens) that pathologists have not been trained to interpret. We discuss the need for artificial intelligence triaging algorithms and explainable analysis methods to assist pathologists or other domain experts in the interpretation of these novel, often complex, large datasets.

The University of Arizona infectious diseases provides telemedicine clinics to the Arizona Department of Corrections (DOC) and Pima County Jail. Beginning in January 2020 there was a sharp drop in the number of monthly consultations following the public health emergency regarding the SARS-CoV-2 pandemic. Only since ending the emergency have the number of consults risen each month to pre-pandemic numbers. However, the nature of consult requests has changed. In this report we document the change from predominately human immunodeficiency virus (HIV) consults to a broader spectrum of infectious-related issues, most noteworthy being infective endocarditis, osteomyelitis, and chronic hepatitis B and C infection, the majority of cases due to intravenous drug injection. Although the DOC and jail underwent major upheavals intramurally due to the pandemic, medical outcomes with the diseases listed above, were excellent. The telemedicine infectious diseases clinics continued to provide timely, effective care for inmates.

Abstract Background Ecological models suggest that interventions targeting specific behaviors are most effective when supported by the environment. This study prospectively examined the interactions between neighborhood walkability and an mHealth intervention in a large-scale, adequately powered trial to increase moderate-to-vigorous physical activity (MVPA). Methods Healthy, insufficiently active adults (N = 512) were recruited purposefully from census block groups ranked on walkability (high/low) and socioeconomic status (SES, high/low). Participants were block-randomized in groups of four to WalkIT Arizona, a 12-month, 2 × 2 factorial trial evaluating adaptive versus static goal setting and immediate versus delayed financial reinforcement delivered via text messages. Participants wore ActiGraph GT9X accelerometers daily for one year. After recruitment, a walkability index was calculated uniquely for every participant using a 500-m street network buffer. Generalized linear mixed-effects hurdle models tested for interactions between walkability, intervention components, and phase (baseline vs. intervention) on: (1) likelihood of any (versus no) MVPA and (2) daily MVPA minutes, after adjusting for accelerometer wear time, neighborhood SES, and calendar month. Neighborhood walkability was probed at 5th, 25th, 50th, 75th, and 95th percentiles to explore the full range of effects. Results Adaptive goal setting was more effective in increasing the likelihood of any MVPA and daily MVPA minutes, especially in lower walkable neighborhoods, while the magnitude of intervention effect declined as walkability increased. Immediate reinforcement showed a greater increase in any and daily MVPA compared to delayed reinforcement, especially relatively greater in higher walkable neighborhoods. Conclusions Results partially supported the synergy hypotheses between neighborhood walkability and PA interventions and suggest the potential of tailoring interventions to individuals’ neighborhood characteristics. Trial Registration Preregistered at clinicaltrials.gov (NCT02717663).

Human and animal diseases have always been reported to be treated by medicinal herbs owing to their constituents. Excess sodium metavanadate is a potential environmental toxin when consumed and could induce oxidative damage leading to various neurological disorders and Parkinsons-like diseases. This study is designed to investigate the impact of the flavonoid Glycoside Fraction of Ginkgo Biloba Extract (GBE) (at 30 mg/kg body weight) on vanadium-treated rats. Animals were divided randomly into four groups: Control (Ctrl, normal saline), Ginkgo Biloba (GIBI, 30mg/kg BWT), Vanadium (VANA, 10 mg/kg BWT) and Vanadium + Ginkgo biloba (VANA + GIBI). Markers of oxidative stress (Glutathione Peroxidase and Catalase) were assessed and found to be statistically increased with GIBI when compared with CTRL and treatment groups. Results from routine staining revealed that the control and GIBI group had a normal distribution of cells and a pronounced increase in cell count respectively compared to the VANA group. When compared to the VANA group, the NeuN photomicrographs revealed that the levels of GIBI were within the normal range (***p < 0.001; ** p < 001). The treatment with GIBI showed a better response by increasing the neuronal cells in the VANA+GIBI when compared with the VANA group. The NLRP3 Inflammasome photomicrographs denoted that there was a decrease in NLRP3-positive cells in the control and GIBI groups. The treatment group shows fewer cells compared to that of the VANA group. The treatment group shows fewer cells compared to that of the VANA group. The findings of the study confirmed that ginkgo biloba extract via its flavonoid glycoside fraction has favorable impacts in modulating vanadium-induced brain damage with the potential ability to lower antioxidant levels and reduce neuroinflammation.

Abstract Six transmembrane epithelial antigen of the prostate 1 (STEAP1) is a cell surface antigen for therapeutic targeting in prostate cancer. Here, we report broad expression of STEAP1 relative to prostate-specific membrane antigen (PSMA) in lethal metastatic prostate cancers and the development of a STEAP1-directed chimeric antigen receptor (CAR) T cell therapy. STEAP1 CAR T cells demonstrate reactivity in low antigen density, antitumor activity across metastatic prostate cancer models, and safety in a human STEAP1 knock-in mouse model. STEAP1 antigen escape is a recurrent mechanism of treatment resistance and is associated with diminished tumor antigen processing and presentation. The application of tumor-localized interleukin-12 (IL-12) therapy in the form of a collagen binding domain (CBD)-IL-12 fusion protein combined with STEAP1 CAR T cell therapy enhances antitumor efficacy by remodeling the immunologically cold tumor microenvironment of prostate cancer and combating STEAP1 antigen escape through the engagement of host immunity and epitope spreading.

Grasslands are among the most impacted ecosystems globally. In the midcontinent of North America, a > 80% loss of grasslands has made their conservation a major priority for resource managers. Grassland ecosystems evolved under periodic disturbances; consequently, grassland management often involves regular actions such as grazing, haying, or burning to maintain ecosystem integrity. The timing of such practices has direct implications on grassland ecology, agricultural economics, and survival and fecundity of grassland nesting birds (hereafter grassland birds). We conducted a meta-analysis on the nesting phenology of grassland birds throughout North America, focusing on nest-survival literature. We constructed a well-fitting model to predict median date of expected nest departure (hereafter fledge date) for grassland birds across the midcontinent. Predictions from our model demonstrate considerable spatial variation in median nesting phenology that is predictable using a spatially explicit spring phenology index. Median fledge dates were 8 or 13 days earlier in years of extreme weather conditions (dry or wet, respectively) than in years of average conditions. Species that generally nest in taller vegetation tended to have later median nest phenologies than those using shorter vegetation. Our results incorporate the most rigorous information available in the literature on nesting phenology of 36 grassland bird species and improve information available to managers about nesting phenology of grassland birds in the midcontinent of North America. Our predictions approximate the day when one-half of the nesting efforts would be complete for a given area within the midcontinent grasslands and can inform management and conservation decisions about the timing of management actions in grassland ecosystems.

Cerebral cavernous malformations occur in about 0.4–0.5 % of the population. They account for about 5–13 % of all vascular malformations of the central nervous system, commonly occurring in the cerebral parenchyma. Very few cases of cavernomas arising from the convexity dura mater have been reported in literature. Cavernous malformations arising from the dura were earlier termed “dural-based cavernous angioma“, ”dural-based cavernous malformation“, ”dural cavernous angioma“ or ”extra-axial cavernous angioma”. Currently they have been classified as “other” venous malformation as per the recent ISSVA classification. Our patient, a 41 year old lady presented with complaints of low back pain radiating to the left lower limb of 20 days duration. During evaluation of associated headache she was found to have a left parietal dural based lesion suggestive of meningioma. Patient underwent craniotomy and excision of lesion. Intraop and histopathological findings were suggestive of dura based cavernous angioma of the cerebral convexity. This case is being reported for its rarity.

Recent declines of grassland bird populations in North America are linked to habitat loss and fragmentation associated with agricultural practices. One tool used to conserve soil, water and wildlife habitat on agricultural fields is the U.S. Department of Agriculture’s Conservation Reserve Program (CRP), the largest agricultural conservation program in the United States. Managers and conservationists recognize CRP as an important component of conserving grassland birds in the central portion of the United States. However, recent widespread expiration of CRP contracts could negatively influence grassland bird populations. Few studies have evaluated how former CRP-enrolled fields may function as grassland bird habitat. In this paper, we analyzed data from a long-term (1990–2017) study aimed at comparing grassland bird abundance (24 species) between idled CRP grasslands and fields where the CRP contracts expired. Some of these fields where contracts expired were maintained as pasture or hayland, and others were converted back to cropland. Estimated abundances of most species were considerably higher in idled CRP than in fields with expired CRP contracts. Post-CRP land use also appeared to affect most bird abundances, with lower abundance in grazed grasslands and haylands relative to idled CRP, but higher abundance than cropland. The responses of obligate and facultative grassland specialists to post-CRP management varied among species, with some being negative and some being positive depending on post-CRP land use, which is unsurprising given the variable habitat requirements of grassland birds. Our results have implications for wildlife managers who must design conservation strategies around the land use decisions of private landowners. Our results support the idea of maintaining a mosaic of undisturbed CRP grasslands and post-CRP grasslands that are hayed or grazed, which should guarantee some undisturbed nesting cover in the landscape for some bird species and some disturbed grasslands that may have long-term benefits for other species.

Abstract Introduction Physical activity is important for children’s health and well-being. Supportiveness for physical activity of home and neighborhood environments may affect children’s PA, but most studies are cross-sectional. We examined environmental predictors of change in children’s physical activity over two years. Methods Data were from the longitudinal, observational cohort study, ‘Neighborhood Impact on Kids’. Participants were children (initially aged 6–12 years) and their parent/caregiver (n = 727 dyads) living in neighborhoods throughout San Diego County, California and King County (Seattle area), Washington, USA. Children’s moderate-to-vigorous physical activity (MVPA) was measured using accelerometers at T1 (Time 1 or baseline, 2007–2009) and T2, the two-year follow-up. At T1, parents survey-reported on physical activity (PA) equipment at home and demographics. Neighborhood environment was measured using spatial data in Geographic Information Systems (intersection density; park availability) and in-person audits (informal play space near home; park-based PA facilities; land use; support for walking/cycling). Generalized additive mixed models estimated total effects, then direct effects, of environmental attributes on MVPA at T1. Two-way moderating effects of child’s sex and age were examined at T1. To examine associations of environmental exposures with changes in MVPA, we estimated interaction effects of environmental attributes on the association between time and MVPA. Results On average, children accumulated 146 min/day (standard deviation or SD = 53) of MVPA at T1, and 113 (SD = 58) min/day at T2. There were no significant total or direct effects of environmental attributes on MVPA at T1, and no significant two-way interaction effects of child’s age and sex for T1 MVPA. Having informal play spaces proximal to home with more amenities was associated with less MVPA decline from T1 to T2. Higher residential density, higher land use mix, and higher number of PA facilities in nearby parks were unexpectedly associated with greater MVPA decline. Conclusion Higher quality informal play spaces close to home may help offset declines in MVPA during middle childhood, as they may promote unstructured active play with opportunities for parental or neighbor surveillance. Unexpectedly, environmental factors consistent with higher walkability were associated with greater declines in children’s MVPA. As physical activity differs across the lifespan, so may environmental factors that facilitate it.

The limited availability of peer-reviewed scientific evidence in the cannabis industry has led many companies to rely on techniques derived from non-peer-reviewed sources for their practices. This study begins by examining the literature on the cultivation of C. sativa, investigating optimal conditions and their effects on growth, and characterising the requirements for greenhouse monitoring and control. A systematic review of current technological approaches is then conducted. The review demonstrates that technology-based control of greenhouse environments has the potential to surpass manual or traditional rule-based management techniques by reducing costs and increasing yields. However, the adoption of these technologies is impeded by the lack of publicly available labelled data on growth, pest and disease, environmental, and yield data of multiple indoor cultivation cycles. Currently, much of the research in this field is conducted privately by companies in the cannabis industry. This study recognises substantial gaps in research surrounding C. sativa cultivation and emphasises the opportunity for new research to address the absence of available C. sativa datasets and peer-reviewed scientific studies outside of private endeavours.

Richard N van Zyl-Smit,1 Kenneth R Chapman,2 Huib AM Kerstjens,3 Christian Gessner,4 Hironori Sagara,5 Ana-Maria Tanase,6 Motoi Hosoe,6 Abhijit Pethe,7 David Lawrence,6 Hanns-Christian Tillmann,8 Peter D’Andrea7 1Division of Pulmonology and UCT Lung Institute, University of Cape Town, Cape Town, South Africa; 2Division of Respiratory Medicine, Department of Medicine, University of Toronto, Toronto, Ontario, Canada; 3Department of Pulmonology, University of Groningen, University Medical Center Groningen, and Groningen Research Institute for Asthma and COPD, Groningen, the Netherlands; 4Universitätsklinikum Leipzig, Germany POIS Leipzig GbR, Leipzig, Germany; 5Department of Medicine, Division of Respiratory Medicine and Allergology, Showa University School of Medicine, Tokyo, Japan; 6Novartis Pharma AG, Basel, Switzerland; 7Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 8Novartis Institutes for BioMedical Research, Translational Medicine, Basel, SwitzerlandCorrespondence: Ana-Maria Tanase, Novartis Pharma AG, Fabrikstrasse 4, Novartis Campus, Basel, Switzerland, Tel +41 79 899 98 22, Email ana-maria.tanase@novartis.comBackground: Once-daily, single-inhaler mometasone furoate/indacaterol acetate/glycopyrronium bromide (MF/IND/GLY, an ICS/LABA/LAMA) and MF/IND (an ICS/LABA) via Breezhaler® have been approved for the maintenance treatment of patients with asthma inadequately controlled with medium-or high-dose ICS or medium-or high-dose ICS/LABA treatment.Objective: Once-daily (o.d.) formulations of MF/IND/GLY and MF/IND at different MF dose strengths have been compared with twice-daily (b.i.d.) fluticasone propionate/salmeterol xinafoate (FLU/SAL), and b.i.d. FLU/SAL+ o.d. tiotropium (TIO) in the PALLADIUM, IRIDIUM and ARGON studies.Methods: The similarity in study design and consistent outcomes in these studies prompted the pooling of data in this review to better characterise these novel once-daily controller formulations.Results: Pooled data from PALLADIUM and IRIDIUM studies showed comparable or greater efficacy with o.d. MF/IND formulations versus b.i.d. FLU/SAL. The o.d. MF/IND/GLY was superior to b.i.d. FLU/SAL in the IRIDIUM study, and similar to, if not more efficacious than b.i.d. FLU/SAL + o.d. TIO in the ARGON study.Conclusion: These formulations therefore provide novel once-daily treatment options for patients across asthma severity and flexibility for clinicians to step-up or step-down the treatment using the same device and formulations.Keywords: mometasone/indacaterol/glycopyrronium, mometasone/indacaterol, fluticasone/salmeterol, tiotropium, bronchodilator, lung function, asthma control, exacerbation

Summary: 3′ untranslated region (3′ UTR) somatic mutations represent a largely unexplored avenue of alternative oncogenic gene dysregulation. To determine the significance of 3′ UTR mutations in disease, we identify 3′ UTR somatic variants across 185 advanced prostate tumors, discovering 14,497 single-nucleotide mutations enriched in oncogenic pathways and 3′ UTR regulatory elements. By developing two complementary massively parallel reporter assays, we measure how thousands of patient-based mutations affect mRNA translation and stability and identify hundreds of functional variants that allow us to define determinants of mutation significance. We demonstrate the clinical relevance of these mutations, observing that CRISPR-Cas9 endogenous editing of distinct variants increases cellular stress resistance and that patients harboring oncogenic 3′ UTR mutations have a particularly poor prognosis. This work represents an expansive view of the extent to which disease-relevant 3′ UTR mutations affect mRNA stability, translation, and cancer progression, uncovering principles of regulatory functionality and potential therapeutic targets in previously unexplored regulatory regions.

Summary: Background: In a parallel-group, international, phase 3 study (ClinicalTrials.gov NCT04762680), we evaluated prototype (D614) and Beta (B.1.351) variant recombinant spike protein booster vaccines with AS03-adjuvant (CoV2 preS dTM-AS03). Methods: Adults, previously primed with mRNA (BNT162b2, mRNA-1273), adenovirus-vectored (Ad26.CoV2.S, ChAdOx1nCoV-19) or protein (CoV2 preS dTM-AS03 [monovalent D614; MV(D614)]) vaccines were enrolled between 29 July 2021 and 22 February 2022. Participants were stratified by age (18–55 and ≥ 56 years) and received one of the following CoV2 preS dTM-AS03 booster formulations: MV(D614) (n = 1285), MV(B.1.351) (n = 707) or bivalent D614 + B.1.351 (BiV; n = 625). Unvaccinated adults who tested negative on a SARS-CoV-2 rapid diagnostic test (control group, n = 479) received two primary doses, 21 days apart, of MV(D614). Anti-D614G and anti-B.1.351 antibodies were evaluated using validated pseudovirus (lentivirus) neutralization (PsVN) assay 14 days post-booster (day [D]15) in 18–55-year-old BNT162b2-primed participants and compared with those pre-booster (D1) and on D36 in 18–55-year-old controls (primary immunogenicity endpoints). PsVN titers to Omicron BA.1, BA.2 and BA.4/5 subvariants were also evaluated. Safety was evaluated over a 12-month follow-up period. Planned interim analyses are presented up to 14 days post-last vaccination for immunogenicity and over a median duration of 5 months for safety. Findings: All three boosters elicited robust anti-D614G or -B.1.351 PsVN responses for mRNA, adenovirus-vectored and protein vaccine-primed groups. Among BNT162b2-primed adults (18–55 years), geometric means of the individual post-booster versus pre-booster titer ratio (95% confidence interval [CI]) were: for MV (D614), 23.37 (18.58–29.38) (anti-D614G); for MV(B.1.351), 35.41 (26.71–46.95) (anti-B.1.351); and for BiV, 14.39 (11.39–18.28) (anti-D614G) and 34.18 (25.84–45.22 (anti-B.1.351). GMT ratios (98.3% CI) versus post-primary vaccination GMTs in controls, were: for MV(D614) booster, 2.16 (1.69; 2.75) [anti-D614G]; for MV(B.1.351), 1.96 (1.54; 2.50) [anti-B.1.351]; and for BiV, 2.34 (1.84; 2.96) [anti-D614G] and 1.39 (1.09; 1.77) [anti-B.1.351]. All booster formulations elicited cross-neutralizing antibodies against Omicron BA.2 (across priming vaccine subgroups), Omicron BA.1 (BNT162b2-primed participants) and Omicron BA.4/5 (BNT162b2-primed participants and MV D614-primed participants). Similar patterns in antibody responses were observed for participants aged ≥56 years. Reactogenicity tended to be transient and mild-to-moderate severity in all booster groups. No safety concerns were identified. Interpretation: CoV2 preS dTM-AS03 boosters demonstrated acceptable safety and elicited robust neutralizing antibodies against multiple variants, regardless of priming vaccine. Funding: Sanofi and Biomedical Advanced Research and Development Authority (BARDA).

Traumatic brain injury (TBI) is a significant cause of mortality and morbidity worldwide resulting from falls, car accidents, sports, and blast injuries. TBI is characterized by severe, life-threatening consequences due to neuroinflammation in the brain. Contact and collision sports lead to higher disability and death rates among young adults. Unfortunately, no therapy or drug protocol currently addresses the complex pathophysiology of TBI, leading to the long-term chronic neuroinflammatory assaults. However, the immune response plays a crucial role in tissue-level injury repair. This review aims to provide a better understanding of TBI's immunobiology and management protocols from an immunopathological perspective. It further elaborates on the risk factors, disease outcomes, and preclinical studies to design precisely targeted interventions for enhancing TBI outcomes.

Background: Disturbance in naturally-occurring anticoagulants may contribute to the hypercoagulable state in COVID-19. This study determined the plasma antigen levels of protein C (PC), protein S (PS), antithrombin-III (AT-III), and thrombomodulin (TM) before treatment and after recovery from COVID-19. Materials and Methods: This cross-sectional study, conducted from February to August 2022 at Kumasi South Hospital, recruited sixty-five RT-PCR-confirmed COVID-19 participants. A venous blood sample was taken for full blood count (FBC) analysis using a 3-part fully automated haematology analyzer, and PC, PS, AT-III, and TM antigen levels measured using ELISA. The data were analyzed using SPSS version 26.0. P

Abstract Glioblastoma is the most lethal form of brain tumor with a recurrence rate of almost 90% and a survival time of only 15 months post-diagnosis. It is a highly heterogeneous, aggressive, and extensively studied tumor. Multiple studies have proposed therapeutic approaches to mitigate or improve the survival for patients with glioblastoma. In this article, we review the loss of the 5′-methylthioadenosine phosphorylase (MTAP) gene as a potential therapeutic approach for treating glioblastoma. MTAP encodes a metabolic enzyme required for the metabolism of polyamines and purines leading to DNA synthesis. Multiple studies have explored the loss of this gene and have shown its relevance as a therapeutic approach to glioblastoma tumor mitigation; however, other studies show that the loss of MTAP does not have a major impact on the course of the disease. This article reviews the contrasting findings of MTAP loss with regard to mitigating the effects of glioblastoma, and also focuses on multiple aspects of MTAP loss in glioblastoma by providing insights into the known findings and some of the unexplored areas of this field where new approaches can be imagined for novel glioblastoma therapeutics.

Abstract Background The COVID-19 pandemic disrupted life in extraordinary ways impacting health and daily mobility. Public transit provides a strategy to improve individual and population health through increased active travel and reduced vehicle dependency, while ensuring equitable access to jobs, healthcare, education, and mitigating climate change. However, health safety concerns during the COVID-19 pandemic eroded ridership, which could have longstanding negative consequences. Research is needed to understand how mobility and health change as the pandemic recedes and how transit investments impact health and equity outcomes. Methods The TROLLEY (TRansit Opportunities for HeaLth, Livability, Exercise and EquitY) study will prospectively investigate a diverse cohort of university employees after the opening of a new light rail transit (LRT) line and the easing of campus COVID-19 restrictions. Participants are current staff who live either 2 miles from LRT, with equal distribution across economic and racial/ethnic strata. The primary aim is to assess change in physical activity, travel mode, and vehicle miles travelled using accelerometer and GPS devices. Equity outcomes include household transportation and health-related expenditures. Change in health outcomes, including depressive symptoms, stress, quality of life, body mass index and behavior change constructs related to transit use will be assessed via self-report. Pre-pandemic variables will be retrospectively collected. Participants will be measured at 3 times over 2 years of follow up. Longitudinal changes in outcomes will be assessed using multilevel mixed effects models. Analyses will evaluate whether proximity to LRT, sociodemographic, and environmental factors modify change in outcomes over time. Discussion The TROLLEY study will utilize rigorous methods to advance our understanding of health, well-being, and equity-oriented outcomes of new LRT infrastructure through the COVID-19 recovery period, in a sample of demographically diverse adult workers whose employment location is accessed by new transit. Results will inform land use, transportation and health investments, and workplace interventions. Findings have the potential to elevate LRT as a public health priority and provide insight on how to ensure public transit meets the needs of vulnerable users and is more resilient in the face of future health pandemics. Trial registration The TROLLEY study was registered at ClinicalTrials.gov ( NCT04940481 ) June 17, 2021, and OSF Registries ( https://doi.org/10.17605/OSF.IO/PGEHU ) June 24, 2021, prior to participant enrollment.

Abstract Background A better understanding of the extent to which psychosocial and environmental correlates of physical activity are specific to locations would inform intervention optimization. Purpose To investigate cross-sectional associations of location-general and location-specific variables with physical activity and sedentary time in three common locations adolescents spend time. Methods Adolescents (N = 472,Mage = 14.1,SD = 1.5) wore an accelerometer and global positioning systems (GPS) tracker and self-reported on psychosocial (e.g., self-efficacy) and environmental (e.g., equipment) factors relevant to physical activity and sedentary time. We categorized each survey item based on whether it was specific to a location to generate psychosocial and environmental indices that were location-general or specific to either school, non-school, or home location. Physical activity (MVPA) and sedentary time were based on time/location match to home, school, or all “other” locations. Mixed-effects models investigated the relation of each index with location-specific activity. Results The location-general and non-school physical activity psychosocial indices were related to greater MVPA at school and “other” locations. The school physical activity environment index was related to greater MVPA and less sedentary time at school. The home activity environment index was related to greater MVPA at home. The non-school sedentary psychosocial index was related to less sedentary time at home. Interactions among indices revealed adolescents with low support on one index benefited (i.e., exhibited more optimal behavior) from high support on another index (e.g., higher scores on the location-general PA psychosocial index moderated lower scores on the home PA environment index). Concurrent high support on two indices did not provide additional benefit. Conclusions No psychosocial or environment indices, including location-general indices, were related to activity in all locations. Most of the location-specific indices were associated with activity in the matching location(s). These findings provide preliminary evidence that psychosocial and environmental correlates of activity are location specific. Future studies should further develop location-specific measures and evaluate these constructs and whether interventions may be optimized by targeting location-specific psychosocial and environmental variables across multiple locations.

Assessments of health variables in wild animal populations have evolved into important tools for characterizing spatiotemporal population trends and fitness, effects of stressors, diseases, and ecosystem health. Blood as a sample matrix can be obtained fairly non-invasively in the field, with preservation and sample processing techniques that allow for readily available routine and advanced diagnostic testing of blood. For wild-caught hawksbill sea turtles (Eretmochelys imbricata) foraging in southeastern Florida, USA, the objectives of this study were to (1) establish reference intervals for hematological and 24 plasma biochemical analytes, (2) determine length-and body condition-specific relationships with blood analytes, and (3) determine how water temperature influenced plasma biochemical analytes. Reference intervals were established for clinically normal juvenile (n = 26) and subadult (n = 39) hawksbills, with descriptive data reported for adult turtles (n = 3). Although subadults (mainly captured at Palm Beach County) were heavier and larger with greater body depth, juveniles (mainly captured at Monroe County) had a higher body condition index. Positive length-specific correlations were identified for packed cell volume, eosinophils, aspartate aminotransferase, phosphorus, cholesterol, glutamate dehydrogenase, total protein, albumin, and globulins, with negative correlations including alkaline phosphatase, creatine kinase, calcium, calcium to phosphorus ratio, and glucose. Subadults had less frequent morphological features of red blood cell regeneration compared to juveniles. These findings provide insight into life-stage class differences regarding hematopoiesis, antigenic stimulation, somatic growth, dietary shifts, nutritional status, osmoregulation, metabolism, physical activity or stress levels, and possible habitat differences. Life-stage class is the likely driver for the observed blood analyte differences, in addition to influences from water temperature. The data herein offer baseline information for a snapshot in time for critically endangered hawksbills inhabiting the Florida reef system and for answering individual-and population-relevant questions of relevance to conservation and population management.

Background: Intradural Extramedullary (IDEM) lesions constitute about 70% of all spinal tumors. Meningioma, schwannoma and neurofibroma are the most common lesions arising in this plane. Cavernoma arising intradurally from a spinal nerve root is one such entity. Case description: A 54 year old gentleman presented with clinical features of L4 radiculopathy and MRI was suggestive of spinal neurofibroma. During surgery a mulberry-like lesion arising from the intradural segment of spinal nerve root was visualized which was excised in toto with the patient showing good recovery postoperatively. Conclusion: Intradural spinal nerve root cavernomas should be considered as a differential diagnosis when an IDEM is suspected, as early intervention offers significantly improved outcomes and prevents morbidity. Due to the rarity of the condition we were able to document just a single case which to an extent limits the ability to infer more information.

Abstract Species often exhibit regionally specific habitat associations, so habitat association models developed in one region might not be accurate or even appropriate for other regions. Three programs to survey wetland‐breeding birds covering (respectively) Great Lakes coastal wetlands, inland Great Lakes wetlands, and the Prairie Pothole Region offer an opportunity to test whether regionally specific models of habitat use by wetland‐obligate breeding birds are transferrable across regions. We first developed independent, regional population density models for four species of wetland‐obligate birds: Pied‐billed Grebe (Podilymbus podiceps), Virginia Rail (Rallus limicola), Sora (Porzana carolina), and American Bittern (Botaurus lentiginosus). We then used adjusted pseudo‐R2 values to compare the amount of variation explained by each model when applied to data collected in each of the three regions. Although certain habitat characteristics, such as emergent vegetation and wetland area, were consistently important across regions, models for each species differed by region—both in variables selected for inclusion and often in the directionality of relationships for common variables—indicating that habitat associations for these species are regionally specific. When we applied a model developed in one region to data collected in another region, we found that explanatory power was reduced in most (71%) models. Therefore, we suggest that ecological analyses should emphasize regionally specific habitat association models whenever possible. Nonetheless, models created from inland Great Lakes wetland data had higher median explanatory power when applied to other regions, and the amount of explanatory power lost by other transferred models was relatively small. Thus, while regionally specific habitat association models are preferable, in the absence of reliable regional data, habitat association models developed in one region may be applied to another region, but the results need to be cautiously interpreted. Additionally, we found that median explanatory power was higher when local‐scale habitat characteristics were included in the models, indicating that regionally specific models should ideally be based on a combination of local‐ and landscape‐scale habitat characteristics. Conservation practitioners can leverage such regionally specific models and associated monitoring data to help prioritize areas for management activities that contribute to regional conservation efforts.

Prostate-specific membrane antigen (PSMA) is an important cell surface target in prostate cancer. There are limited data on the heterogeneity of PSMA tissue expression in metastatic castration-resistant prostate cancer (mCRPC). Furthermore, the mechanisms regulating PSMA expression (encoded by the FOLH1 gene) are not well understood. Here, we demonstrate that PSMA expression is heterogeneous across different metastatic sites and molecular subtypes of mCRPC. In a rapid autopsy cohort in which multiple metastatic sites per patient were sampled, we found that 13 of 52 (25%) cases had no detectable PSMA and 23 of 52 (44%) cases showed heterogeneous PSMA expression across individual metastases, with 33 (63%) cases harboring at least 1 PSMA-negative site. PSMA-negative tumors displayed distinct transcriptional profiles with expression of druggable targets such as MUC1. Loss of PSMA was associated with epigenetic changes of the FOLH1 locus, including gain of CpG methylation and loss of histone 3 lysine 27 (H3K27) acetylation. Treatment with histone deacetylase (HDAC) inhibitors reversed this epigenetic repression and restored PSMA expression in vitro and in vivo. Collectively, these data provide insights into the expression patterns and regulation of PSMA in mCRPC and suggest that epigenetic therapies — in particular, HDAC inhibitors — can be used to augment PSMA levels.

The cerebrospinal fluid (CSF) is a clear ultrafiltrate of blood that envelopes and protects the central nervous system while regulating neuronal function through the maintenance of interstitial fluid homeostasis in the brain. Due to its anatomic location and physiological functions, the CSF can provide a reliable source of biomarkers for the diagnosis and treatment monitoring of different neurological diseases, including neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and primary and secondary brain malignancies. The incorporation of CSF biomarkers into the drug discovery and development can improve the efficiency of drug development and increase the chances of success. This review aims to consolidate the current use of CSF biomarkers in clinical practice and explore future perspectives for the field.

This study sought to investigate the anthropometric traits and physical capabilities of team handball players, categorized based on their playing positions. A total of 50 male players (age: 27.4 ± 4.2 years; body mass: 92.8 ± 14.2 kg; height: 1.87 ± 0.08 m; body mass index (BMI): 26.3 ± 3.3 kg/m2) were categorized as Backs (12), Wings (14), Pivots (14), and Goalkeepers (10). The measurements included squat jumps (SJs), countermovement jumps (CMJs), sprint timings over 15 and 30 m, upper and lower limb muscle volume, change-of-direction T-Half test performance, and Yo-Yo intermittent recovery test performance. Depending on the position, the largest differences were detected for 30 m sprint (ηp2 = 0.72), 15 m sprint (ηp2 = 0.71), T-Half test (ηp2 = 0.41), half squat (ηp2 = 0.35), and bicipital skinfold of a throwing arm (ηp2 = 0.34). Bicipital skinfold showed the highest number (three) of relevant (r > 0.5) relationships, especially in sprinting (sprint 15 m: r = 0.528; sprint 30 m: r = 0.503) and change-of-direction ability (T-Half test: r = 0.518). Differences in physical performance and body type according to playing positions emphasize the value of goalkeeper-specific training and scouting for handball players, with a particular emphasis on both. This information might be helpful for optimizing position-specific training regimes.

Abstract Background Walkability indices have been developed and linked to behavioural and health outcomes elsewhere in the world, but not comprehensively for Europe. We aimed to 1) develop a theory-based and evidence-informed Dutch walkability index, 2) examine its cross-sectional associations with total and purpose-specific walking behaviours of adults across socioeconomic (SES) and urbanisation strata, 3) explore which walkability components drive these associations. Methods Components of the index included: population density, retail and service density, land use mix, street connectivity, green space, sidewalk density and public transport density. Each of the seven components was calculated for three Euclidean buffers: 150 m, 500 m and 1000 m around every 6-digit postal code location and for every administrative neighbourhood in GIS. Componential z-scores were averaged, and final indices normalized between 0 and 100. Data on self-reported demographic characteristics and walking behaviours of 16,055 adult respondents (aged 18–65) were extracted from the Dutch National Travel Survey 2017. Using Tobit regression modelling adjusted for individual- and household-level confounders, we assessed the associations between walkability and minutes walking in total, for non-discretionary and discretionary purposes. By assessing the attenuation in associations between partial indices and walking outcomes, we identified which of the seven components drive these associations. We also tested for effect modification by urbanization degree, SES, age and sex. Results In fully adjusted models, a 10% increase in walkability was associated with a maximum increase of 8.5 min of total walking per day (95%CI: 7.1–9.9). This association was consistent across buffer sizes and purposes of walking. Public transport density was driving the index’s association with walking outcomes. Stratified results showed that associations with minutes of non-discretionary walking were stronger in rural compared to very urban areas, in neighbourhoods with low SES compared to high SES, and in middle-aged (36–49 years) compared to young (18–35 years old) and older adults (50–65 years old). Conclusions The walkability index was cross-sectionally associated with Dutch adult’s walking behaviours, indicating its validity for further use in research.

Abstract The development of a shared data infrastructure across health systems could improve research, clinical care, and health policy across a spectrum of diseases, including sepsis. Awareness of the potential value of such infrastructure has been heightened by COVID-19, as the lack of a real-time, interoperable data network impaired disease identification, mitigation, and eradication. The Sepsis on FHIR collaboration establishes a dynamic, federated, and interoperable system of sepsis data from 55 hospitals using 2 distinct inpatient electronic health record systems. Here we report on phase 1, a systematic review to identify clinical variables required to define sepsis and its subtypes to produce a concept mapping of elements onto Fast Healthcare Interoperability Resources (FHIR). Relevant papers described consensus sepsis definitions, provided criteria for sepsis, severe sepsis, septic shock, or detailed sepsis subtypes. Studies not written in English, published prior to 1970, or “grey” literature were prospectively excluded. We analyzed 55 manuscripts yielding 151 unique clinical variables. We then mapped variables to their corresponding US Core FHIR resources and specific code values. This work establishes the framework to develop a flexible infrastructure for sharing sepsis data, highlighting how FHIR could enable the extension of this approach to other important conditions relevant to public health.

Introduction: This study aimed to compare 10–12-year-old Qatari male soccer players (n = 45) regarding different dimensions (anthropometric, academic and physical performance).Methods: Anthropometric parameters (body mass, fat percentage (%BF), body mass index (BMI)) academic achievement (mathematics and science grade point average [GPA]) and physical performance [Yo-Yo Intermittent Recovery Test (level 1), squat jumps (SJ), counter-movement jumps (CMJ), stork balance test, 10 and 15 m sprint tests, T-half test for change-of-direction (CoD) ability, hand-grip strength, medicine ball throw (MBT)] were measured. Schoolchild soccer players were divided into three groups: 12-year-old players (U12; n = 16), 11-year-old players (U11; n = 14), 10-year-old players (U10; n = 15).Results: Apart from mathematics, Yo-Yo IR1 and 10 m sprint, all performance parameters showed significant age effects. The largest age-related difference was observed for 15 m sprint (p < 0.001). Both adjacent age groups displayed significant differences for 15 sprint (U10 vs. U11: p = 0.015; U11 vs. U12: p = 0.023). Concerning academic performance, a significant age effect was found for science (p < 0.001). There was a main age effect on academic performance difference between U10 and U11 (p = 0.007). Academic parameters did not correlate with any physical performance parameter or anthropometric parameter. The strongest correlations were detected for body height and agility T-half test (r = −0.686) and medicine ball throw (r = 0.637). The biological maturity was strongly correlated with handgrip strength (r = −0.635).Discussion: Soccer coaches and physical education teachers can use these data as reference values for evaluation of school-aged soccer players, and for ascertaining specific training targets. Obviously, short sprinting ability and aerobic capacity are not functions of age and need a specific training for significant improvements.

Neoantigen vaccines are based on epitopes of antigenic parts of mutant proteins expressed in cancer cells. These highly immunogenic antigens may trigger the immune system to combat cancer cells. Improvements in sequencing technology and computational tools have resulted in several clinical trials of neoantigen vaccines on cancer patients. In this review, we have looked into the design of the vaccines which are undergoing several clinical trials. We have discussed the criteria, processes, and challenges associated with the design of neoantigens. We searched different databases to track the ongoing clinical trials and their reported outcomes. We observed, in several trials, the vaccines boost the immune system to combat the cancer cells while maintaining a reasonable margin of safety. Detection of neoantigens has led to the development of several databases. Adjuvants also play a catalytic role in improving the efficacy of the vaccine. Through this review, we can conclude that the efficacy of vaccines can make it a potential treatment across different types of cancers.

Machine learning has been leveraged for image analysis applications throughout a multitude of subspecialties. This position paper provides a perspective on the evolutionary trajectory of practical deep learning tools for genitourinary pathology through evaluating the most recent iterations of such algorithmic devices. Deep learning tools for genitourinary pathology demonstrate potential to enhance prognostic and predictive capacity for tumor assessment including grading, staging, and subtype identification, yet limitations in data availability, regulation, and standardization have stymied their implementation.

Artificial Intelligence is a tool poised to transform healthcare, with use in diagnostics and therapeutics. The widespread use of digital pathology has been due to the advent of whole slide imaging. Cheaper storage for digital images, along with unprecedented progress in artificial intelligence, have paved the synergy of these two fields. This has pushed the limits of traditional diagnosis using light microscopy, from a more subjective to a more objective method of looking at cases, incorporating grading too. The grading of histopathological images of urothelial carcinoma of the urinary bladder is important with direct implications for surgical management and prognosis.In this study, the aim is to classify urothelial carcinoma into low and high grade based on the WHO 2016 classification. The hematoxylin and eosin-stained transurethral resection of bladder tumor (TURBT) samples of both low and high grade non-invasive papillary urothelial carcinoma were digitally scanned. Patches were extracted from these whole slide images to feed into a deep learning (Convolution Neural Network: CNN) model. Patches were segregated if they had tumor tissue and only included for model training if a threshold of 90% of tumor tissue per patch was seen. Various parameters of the deep learning model, known as hyperparameters, were optimized to get the best accuracy for grading or classification into low- and high-grade urothelial carcinoma. The model was robust with an overall accuracy of 90% after hyperparameter tuning. Visualization in the form of a class activation map using Grad-CAM was done. This indicates that such a model can be used as a companion diagnostic tool for grading of urothelial carcinoma. The probable causes of this accuracy are summarized along with the limitations of this study and future work possible.

Abstract Background Walkability is a popular term used to describe aspects of the built and social environment that have important population-level impacts on physical activity, energy balance, and health. Although the term is widely used by researchers, practitioners, and the general public, and multiple operational definitions and walkability measurement tools exist, there are is no agreed-upon conceptual definition of walkability. Method To address this gap, researchers from Memorial University of Newfoundland hosted “The Future of Walkability Measures Workshop” in association with researchers from the Canadian Urban Environmental Health Research Consortium (CANUE) in November 2017. During the workshop, trainees, researchers, and practitioners worked together in small groups to iteratively develop and reach consensus about a conceptual definition and name for walkability. The objective of this paper was to discuss and propose a conceptual definition of walkability and related concepts. Results In discussions during the workshop, it became clear that the term walkability leads to a narrow conception of the environmental features associated with health as it inherently focuses on walking. As a result, we suggest that the term Active Living Environments, as has been previously proposed in the literature, are more appropriate. We define Active Living Environments (ALEs) as the emergent natural, built, and social properties of neighbourhoods that promote physical activity and health and allow for equitable access to health-enhancing resources. Conclusions We believe that this broader conceptualization allows for a more comprehensive understanding of how built, natural, and social environments can contribute to improved health for all members of the population.

Context: U.S. Latinas have lower rates of contraceptive use and report more negative counseling experiences compared to non-Latina white women. Patient-centered approaches to contraceptive counseling are desired among Latinas and are also associated with patient satisfaction; yet, clinicians may not always use counseling methods that best support decision-making among marginalized groups. Objective: To examine Latinas' expectations of physician communication about contraceptive side effects, reported importance of personal knowledge about side effects, and the association of these with contraceptive use and use consistency. Materials and Methods: One hundred three self-identified Latinas aged 15?29 years at two urban federally qualified health centers completed a survey measuring factors associated with contraceptive use and consistency. Bivariate analysis was used to assess demographic and contraceptive information preferences. Associations between categorical variables were assessed using two-sided Fisher's exact tests. Continuous variables were compared using two-sided t-test. Results: The majority of respondents (85%) expected physicians to tell them about birth control side effects and reported that this information is important to use contraception, regardless of current contraceptive use. Among inconsistent and nonusers, importance of knowledge of side effects depended on expectations of information-sharing from physicians (p?0.05). Conclusions: Expectations regarding side effect information-sharing by physicians and patient knowledge of side effects are important for the contraceptive decision-making process of this Latina group, regardless of contraceptive use. Clinicians engaging in contraceptive counseling should focus on providing clear and accurate information about side effects of discussed methods to facilitate informed decision-making and equitable, patient-centered contraceptive care for this vulnerable population.

Abstract We present a method to directly visualise a statistical analysis of skyrmion defect alignment at grain boundaries in the skyrmion host $$\hbox {Cu}_2$$ Cu 2 OSeO3. Using Lorentz transmission electron microscopy, we collected large data sets with several hundreds of frames containing skyrmion lattices with grain boundaries in them. To address the behaviour of strings of dislocations in these grain boundaries, we developed an algorithm to automatically extract and classify strings of dislocations separating the grains. This way we circumvent the problem of having to create configurations with well-defined relative grain orientations by performing a statistical analysis on a dynamically rearranging image sequence. With this statistical method, we are able to experimentally extract the relationship between grain boundary alignment and defect spacing and find an agreement with geometric expectations. The algorithms used can be extended to other types of lattices such as Abrikosov lattices or colloidal systems in optical microscopy.

Background: This cross-sectional study examined gender differences in physical activity (PA), body mass index, sedentary behavior (SB), and academic performance (AP) in school-aged children in Qatar. Methods: Fifty-two schoolchildren (age: 11.9 ± 0.6 years) were assigned to gender-adjusted groups (female; n = 29). AP was calculated using the grade point averages (GPA) in Mathematics, Science, and Arabic. Additionally, the Short Form of the International Physical Activity Questionnaire (IPAQ) was utilized. Results: Four parameters (peak height velocity [PHV], science, Arabic, vigorous PA) showed relevant gender effects (p < 0.05 and ηp2 > 0.10). The largest gender effect was calculated for PHV (p < 0.001, ηp2 = 0.45). PHV was markedly higher for males (1.65 ± 0.90) than for females (0.36 ± 0.37). Females showed a higher performance level in science (82.9 ± 8.61 vs. 77.0 ± 8.76) and Arabic (80.9 ± 8.25 vs. 73.0 ± 8.22). A significant gender difference (p = 0.002, ηp2 = 0.18) was evident for vigorous MET-minutes/week (males: 1318 ± 932 vs. females: 646 ± 525). In conclusion, males exhibited the greatest amount of moderate and vigorous PA. Females spent the greatest time sitting. Arabic was different by gender, and science AP was dependent upon gender. Conclusions: These data suggest subjects in middle school are sensitive to gender, but not necessarily influenced by PA or SB at this age. Encouraging a school-based program and an after-school health club characterized by gender sensitive strategies consisting of a health class and physical education curriculum support the unique needs, interests of academic performance, and motor skills to improving health related fitness for girls compared to boys.

In diabetes, possibly the most significant site of microvascular damage is the kidney. Due to diabetes and/or other co-morbidities, such as hypertension and age-related nephron loss, a significant number of people with diabetes suffer from kidney diseases. Improved diabetic care can reduce the prevalence of diabetic nephropathy (DN); however, innovative treatment approaches are still required. MicroRNA-21 (miR-21) is one of the most studied multipotent microRNAs (miRNAs), and it has been linked to renal fibrosis and exhibits significantly altered expression in DN. Targeting miR-21 offers an advantage in DN. Currently, miR-21 is being pharmacologically silenced through various methods, all of which are in early development. In this review, we summarize the role of miR-21 in the molecular pathogenesis of DN and several therapeutic strategies to use miR-21 as a therapeutic target in DN. The existing experimental interventions offer a way to rectify the lower miRNA levels as well as to reduce the higher levels. Synthetic miRNAs also referred to as miR-mimics, can compensate for abnormally low miRNA levels. Furthermore, strategies like oligonucleotides can be used to alter the miRNA levels. It is reasonable to target miR-21 for improved results because it directly contributes to the pathological processes of kidney diseases, including DN.

It is known that talkers can be recognized by listening to their specific vocal qualities—breathiness and fundamental frequencies. However, talker identification can also occur by focusing on the talkers’ unique articulatory style, which is known to be available auditorily and visually and can be shared across modalities. Evidence shows that voices heard while seeing talkers’ faces are later recognized better on their own compared to the voices heard alone. The present study investigated whether the facilitation of voice learning through facial cues relies on talker-specific articulatory or nonarticulatory facial information. Participants were initially trained to learn the voices of ten talkers presented either on their own or together with (a) an articulating face, (b) a static face, or (c) an isolated articulating mouth. Participants were then tested on recognizing the voices on their own regardless of their training modality. Consistent with previous research, voices learned with articulating faces were recognized better on their own compared to voices learned alone. However, isolated articulating mouths did not provide an advantage in learning the voices. The results demonstrated that learning voices while seeing faces resulted in better voice learning compared to the voices learned alone.

We describe the novel transcatheter approach, with off-label application of LAA closure device, coiling, and concurrent left anterior descending stenting in the setting of left ventricular (LV) pseudoaneurysm. This case underlines collaboration among interventional cardiology, cardiothoracic, and neurosurgery teams in a challenging, nonsurgical candidate with high risk of LV pseudoaneurysm rupture, and death. (Level of Difficulty: Advanced.)

Randomised controlled trials (RCTs) have long been considered the gold standard of medical evidence. In relation to cannabis based medicinal products (CBMPs), this focus on RCTs has led to very restrictive guidelines in the UK, which are limiting patient access. There is general agreement that RCT evidence in relation to CBPMs is insufficient at present. As well as commercial reasons, a major problem is that RCTs do not lend themselves well to the study of whole plant medicines. One solution to this challenge is the use of real world evidence (RWE) with patient reported outcomes (PROs) to widen the evidence base. Such data increasingly highlights the positive impact medical cannabis can have on patients’ lives. This paper outlines the value of this approach which involves the study of interventions and patients longitudinally under medical care. In relation to CBMPs, RWE has a broad range of advantages. These include the study of larger groups of patients, the use of a broader range and ratio of components of CBMPs, and the inclusion of more and rarer medical conditions. Importantly, and in contrast to RCTs, patients with significant comorbidities–and from a wider demographic profile–can also be studied, so providing higher ecological validity and increasing patient numbers, whilst offering significant cost savings. We conclude by outlining 12 key recommendations of the value of RWE in relation to medical cannabis. We hope that this paper will help policymakers and prescribers understand the importance of RWE in relation to medical cannabis and help them develop approaches to overcome the current situation which is detrimental to patients.

Placenta accreta spectrum (PAS) is a high-risk obstetrical complication associated with significant morbidity and mortality. Here the authors discover a uniquely high prevalence of circulating trophoblasts clusters in PAS and explore their diagnostic potential to augment current diagnostic modalities for the early detection of PAS.