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The ability to effectively identify students for advanced learning opportunities has been an ongoing issue within the field of gifted education. Common criteria to guide the design and evaluation of identification systems has been essentially non-existent. In this article we provide a practical guide for evaluating and reflecting on the effectiveness of identification criteria, namely: CASA (Cost, Alignment, Sensitivity, and Access). To demonstrate their use, the CASA criteria are described and the criteria are applied to a hypothetical district with discussion about decisions and changes to support more equitable identification and services alignment. A checklist is also provided to guide district leaders with applying the CASA criteria to their own identification systems. This article builds upon previous descriptions of CASA that have been published.

This study used data from the National Longitudinal Transition Study 2012 (NLTS 2012) to explore the future goal aspirations of students with extensive support needs who participate in alternate assessments, compared to other students with extensive support needs and to students with other disabilities. We examined students' individualized education program (IEP)/transition planning meeting experiences and postschool goals in relation to their functional, communication, and self-advocacy skills, as well as their school/community support. Students with other disabilities held higher expectations than all students with extensive support needs for future participation in postsecondary education, employment, independent living, and financial independence. All students had higher postschool goal expectations than their parents. Implications for supporting students with extensive support needs and directions for future research and practice are discussed.

Purpose: This study was to investigate the factors associated with preventable hospitalization due to ambulatory care sensitive conditions (ACSCs) in children with autism. Methods: Using secondary data from the U.S. Nationwide Inpatient Sample (NIS), multivariable regression analyses were conducted to determine the potential effect of race and income level on the likelihood of inpatient stays for ACSCs among autistic children. Pediatric ACSCs included three acute conditions (dehydration, gastroenteritis, and urinary infection) and three chronic conditions (asthma, constipation, and diabetes short-term complications). Results: In this analysis, there were 21,733 hospitalizations among children with autism; about 10% were hospitalized due to pediatric ACSCs. Overall, the odds of ACSCs hospitalization were greater among Hispanic and Black autistic children versus White autistic children. Both Hispanic and Black autistic children from the lowest income level had the highest odds to be hospitalized for chronic ACSCs. Conclusion: Inequities of access to health care among racial/ethnic minorities were most notable for autistic children with chronic ACSC conditions.

Electrophoresis is integral to analytical and biochemistry experiences in undergraduate education; however, fundamental principles of the method are often taught in upper-level laboratories through hands-on experiences. A laboratory activity is reported that teaches the concepts of electrophoretic mobility and electroosmotic flow. A single reuseable instrument, called a mini-E, costs 37 USD and consists of a DC power supply, a voltmeter, platinum electrodes, and a chip cast in polydimethylsiloxane. This activity uses common reagents costing only 0.02 USD per student. Experiments are devised that allow students to investigate the properties of electrophoretic flow and electroosmotic flow by separating the two commonly used food dyeing agents Brilliant Blue FCF and Allura Red AC in vinegar and in a solution of ammonium hydroxide. A dark-purple mixture of these dyes is separated into red and blue bands that are easily visualized. The migration order of the dyes differs when the separation is performed under conditions of reversed polarity and suppressed electroosmotic flow (vinegar) compared to conditions of normal polarity and active electroosmotic flow (ammonium hydroxide). When delivered to chemistry majors, students had a significant gain in their ability to apply the concepts of electroosmosis and electrophoresis to predict analyte migration. Although this activity targets upper-level chemistry content, it can also be adapted for other laboratory experiences.

Toward the development of a new parent-rating for insomnia, this multi-site qualitative study explored sleep problems and related impacts in children with autism spectrum disorder (ASD) and their families. To ensure content validity of the measure, we conducted six focus groups with caregivers (N = 25) of 24 children (age 3 to 18 years) with ASD. Based on parent report, all children had a history of mild or greater insomnia. The focus group transcripts were systematically coded to identify major themes. Verbatim comments from caretakers were used to generate 134 candidate items. Further review by the research team and an expert panel followed by individual cognitive interviews with 12 parents reduced the item bank to 40. The thematic analysis of focus group transcripts identified 7 categories: (1) Trouble falling asleep; (2) trouble staying asleep; (3) early morning waking; (4) bedtime routines; (5) parental strategies for bedtime management; (6) impact of sleep problems on the child; and (7) impact of sleep problems on the family. The Flesch Kincaid Grade Level of the 40-item version was 7.2 (seventh grade reading level). Insomnia in children with ASD shares features in common with insomnia in the general pediatric population. However, perhaps owing to autistic features such as insistence on sameness, sensory sensitivities, communication impairments, insomnia in children with ASD appears to have unique behavioral manifestations. Content validity and item clarity of the 40-item bank were supported by expert panel review and cognitive interviews with caregivers of children with ASD.

Abstract Planners managing coastal flood risk under a constrained computational budget face a tradeoff. Simulating many time periods or scenarios limits how many storm simulations can be run on each landscape. In this analysis, we present a deep learning model to predict storm surge as a function of storm parameters but also landscape features and boundary conditions (e.g., sea level). It is trained on peak surge elevations from Advanced Circulation (ADCIRC) hydrodynamic simulations of coastal Louisiana in a 2020 baseline and decadal periods from 2030 to 2070 under two morphological and climate scenarios. Leave-one-landscape-out cross-validation yielded a 0.086-m RMSE and 0.050-m MAE over 90 storms per landscape and 94,013 geospatial locations. A two-sided Kolmogorov-Smirnov test comparing annual exceedance probability (AEP) estimates from the model predictions to ADCIRC simulations rejected the null hypothesis that the predicted and ADCIRC AEP values were drawn from the same distribution only 1.1% of the time.

Metaproteomics is an increasingly popular methodology that provides information regarding the metabolic functions of specific microbial taxa and has potential for contributing to ocean ecology and biogeochemical studies. A blinded multi-laboratory intercomparison was conducted to assess comparability and reproducibility of taxonomic and functional results and their sensitivity to methodological variables. Euphotic zone samples from the Bermuda Atlantic Time-series Study (BATS) in the North Atlantic Ocean collected by in situ pumps and the autonomous underwater vehicle (AUV) Clio were distributed with a paired metagenome, and one-dimensional (1D) liquid chromatographic data-dependent acquisition mass spectrometry analysis was stipulated. Analysis of mass spectra from seven laboratories through a common bioinformatic pipeline identified a shared set of 1056 proteins from 1395 shared peptide constituents. Quantitative analyses showed good reproducibility: pairwise regressions of spectral counts between laboratories yielded R2 values averaged 0.62±0.11, and a Sørensen similarity analysis of the top 1000 proteins revealed 70 %–80 % similarity between laboratory groups. Taxonomic and functional assignments showed good coherence between technical replicates and different laboratories. A bioinformatic intercomparison study, involving 10 laboratories using eight software packages, successfully identified thousands of peptides within the complex metaproteomic datasets, demonstrating the utility of these software tools for ocean metaproteomic research. Lessons learned and potential improvements in methods were described. Future efforts could examine reproducibility in deeper metaproteomes, examine accuracy in targeted absolute quantitation analyses, and develop standards for data output formats to improve data interoperability. Together, these results demonstrate the reproducibility of metaproteomic analyses and their suitability for microbial oceanography research, including integration into global-scale ocean surveys and ocean biogeochemical models.

Abstract Background Medically tailored meal (MTM) programs provide home-delivered meals to people living with serious illness and poor nutritional status. Client outcome studies have found evidence of decreased healthcare utilization and cost savings associated with MTM program participation, and inconclusive evidence of change in health measures. The purpose of this study was to use a novel observational framework to describe the client profile and change in health outcomes using routinely collected health and program data from a community-based MTM program at MANNA (Philadelphia, PA). Methods Clients reported their self-rated health and experiences of food insecurity and malnutrition. Healthcare providers reported clients’ body mass index, systolic blood pressure, and hemoglobin A1C. These health outcomes, measured at program intake and 3–6 months later, were linked with administrative data for 1,959 clients who completed at least two months of MTM services in 2020, 2021, and 2022. Results Clients exhibited substantial heterogeneity in demographics and health status at intake. Self-reported malnutrition risk decreased significantly over program duration (p

Abstract The NASA Perseverance rover discovered light-toned float rocks scattered across the surface of Jezero crater that are particularly rich in alumina ( ~ 35 wt% Al2O3) and depleted in other major elements (except silica). These unique float rocks have heterogeneous mineralogy ranging from kaolinite/halloysite-bearing in hydrated samples, to spinel-bearing in dehydrated samples also containing a dehydrated Al-rich phase. Here we describe SuperCam and Mastcam-Z observations of the float rocks, including the first in situ identification of kaolinite or halloysite on another planet, and dehydrated phases including spinel and apparent partially dehydroxylated kaolinite. The presence of spinel in these samples is likely detrital in origin, surviving kaolinitization, pointing to an ultramafic origin. However, the association of low hydration with increased Al2O3 abundances suggests heating-induced dehydration which could have occurred during the lithification or impact excavation of these rocks. Given the orbital context of kaolinite-bearing megabreccia in the Jezero crater rim, we propose an origin for these rocks involving intense aqueous alteration of the parent material, followed by dehydration/lithification potentially through impact processes, and dispersion into Jezero crater through flood or impact-related processes.

Abstract Oxygen isotopes (δ 18O) are the most commonly utilized speleothem proxy and have provided many foundational records of paleoclimate. Thus, understanding processes affecting speleothem δ 18O is crucial. Yet, prior calcite precipitation (PCP), a process driven by local hydrology, is a widely ignored control of speleothem δ 18O. Here we investigate the effects of PCP on a stalagmite δ 18O record from central Vietnam, spanning 45 – 4 ka. We employ a geochemical model that utilizes speleothem Mg/Ca and cave monitoring data to correct the δ 18O record for PCP effects. The resulting record exhibits improved agreement with regional speleothem δ 18O records and climate model simulations, suggesting that the corrected record more accurately reflects precipitation δ 18O (δ 18Op). Without considering PCP, our interpretations of the δ 18O record would have been misleading. To avoid misinterpretations of speleothem δ 18O, our results emphasize the necessity of considering PCP as a significant driver of speleothem δ 18O.

Abstract Background The main objective is to discuss why treatment of non-prostate cancers with [177Lu]Lu-PSMA-radioligand achieved only low tumor dose in most published cases, despite high uptake on PSMA PET. We use a patient with renal cell carcinoma as an illustrative example. Furthermore, we discuss how the problem with early washout and low tumor dose might be overcome by using a radionuclide with shorter half-life, matching the target binding residence time. Case presentation [68Ga]Ga-PSMA-11 PET/CT of a 56-year old man with metastatic renal cell carcinoma showed high lesion uptake. One dose of 6.9 GBq [177Lu]Lu-PSMA-I&T was administrated. Post-therapy dosimetry was performed with SPECT/CT and whole-body planar imaging after 5, 24 and 48 h. Doses to target lesions were only 0.2–0.5 Gy. No treatment effect was achieved. Conclusion Rapid tumor washout of [177Lu]Lu-PSMA-I&T and low tumor dose despite high uptake of [68Ga]Ga-PSMA-11 are most likely caused by localization of PSMA-receptors on neovasculature rather than on the tumor cells, and unlike in prostate cancer cells, the PSMA-RL / PSMA-receptor complex is not internalized. To overcome the problem with early washout, the use of a radionuclide with shorter half-life matching the target binding residence time will be needed.

Abstract Substance Use Disorders (SUDs) manifest as persistent drug-seeking behavior despite adverse consequences, with Alcohol Use Disorder (AUD) and Opioid Use Disorder (OUD) representing prevalent forms associated with significant mortality rates and economic burdens. The co-occurrence of AUD and OUD is common, necessitating a deeper comprehension of their intricate interactions. While the causal link between these disorders remains elusive, shared genetic factors are hypothesized. Leveraging public datasets, we employed genomic and transcriptomic analyses to explore conserved and distinct molecular pathways within the dorsolateral prefrontal cortex associated with AUD and OUD. Our findings unveil modest transcriptomic overlap at the gene level between the two disorders but substantial convergence on shared biological pathways. Notably, these pathways predominantly involve inflammatory processes, synaptic plasticity, and key intracellular signaling regulators. Integration of transcriptomic data with the latest genome-wide association studies (GWAS) for problematic alcohol use (PAU) and OUD not only corroborated our transcriptomic findings but also confirmed the limited shared heritability between the disorders. Overall, our study indicates that while alcohol and opioids induce diverse transcriptional alterations at the gene level, they converge on select biological pathways, offering promising avenues for novel therapeutic targets aimed at addressing both disorders simultaneously.

The assessment of Intellectual Disability (ID) under the Individuals With Disabilities Education Improvement Act 2004 (IDEIA; Public Law 108-446, 2004) requires the measurement of both intelligence and adaptive behavior (i.e., conceptual, social, and practical skills). This study expands past research by examining current state special education guidelines based on IDEIA and their alignment with best practices in assessment across all U.S. states and the District of Columbia (DC) for the assessment of ID. Aggregated and disaggregated data pertaining to special education guidelines and recommendations are examined, including cut-scores and confidence intervals, information specific to composite adaptive behavior scores versus domain scores, and multiple informants.

Objective: This study examined the impact of State and Trait anxiety and dietary intake on college students' gastrointestinal symptoms during the COVID-19 pandemic. Participants: A total of 455 students, aged 18-23, from two residential colleges in the midwestern United States participated in the study during April 2021. Methods: An online questionnaire that included the National Cancer Institute Dietary Screener, State-Trait Inventory for Cognitive and Somatic Anxiety, and an adapted version of the Gastrointestinal Symptoms Questionnaire was used. Stepwise multiple regression analyses and Spearman rho correlation coefficients were used to analyze the data. Results: High rates of State-somatic, State-cognitive, and Trait-somatic anxiety were present in our study population. These anxiety subscales and dietary intake predicted 26% and 3.8% of the GI symptoms variance, respectively. Conclusion: State-anxiety and Trait-somatic anxiety are large factors in predicting GI symptoms compared to dietary intake. College students could seek anxiety-reducing techniques to ease GI symptoms.

Attacks on diversity, equity, and inclusion threaten to undo much of the work of creating and maintaining diverse learning and working environments for students, faculty, and staff. In honor of ACPA's 100th anniversary, we reflect on the current threats to the campus racial climate, highlight research that informs our scholarship and practice, and offer strategies for resistance. We close with a consideration of critical hope as necessary to the pursuit of equity-centered work during this turbulent period in higher education.

After-school youth development programs support social-emotional functioning which leads to better academic and behavioral outcomes. This article examines three common predictors of social-emotional functioning individually and concurrently to better understand the role of these predictors in the after-school setting. The common predictors are staff/student relationships, sense of belonging, and program engagement. That data came from 144, 3rd through 8th grade, students across 9 different elementary and middle school sites who regularly attended a large youth development program. Regression analyses were run and the results indicated that each variable was an individually significant predictor of social-emotional functioning. Results from multiple regression analyses demonstrated that there was a better model fit when including all three variables in the same model. Interestingly, the results indicated that program engagement was a strong predictor above and beyond staff/student relationships and sense of belonging on self-management and self-efficacy. Sense of belonging and program engagement both predicted social awareness. Implications of these findings for after-school program planning and development are discussed.

Using a qualitative multiple case study research design, the authors investigated the leadership and collaboration strategies of HBCU administrators seeking to drive queer and trans* student inclusion initiatives on their campuses. Further, organizational challenges were examined to make sense of infrastructure elements that needed to be added to these efforts. Analyzed employing the transformational change process (Kezar & Eckel, 2002), three themes were developed: (1) leadership matters, (2) institutional and external collaboration, and (3) institutionalizing on unstable grounds. Implications for future research, theory, practice, and policy are shared at the conclusion of this manuscript.

Finding all the "gifted" students who would benefit from a gifted and talented service is a perpetual concern. In this article, we focus on how to effectively implement multiple criteria in identification. First, we provide some broad background before introducing three different ways to combine multiple data points (AND, OR, and MEAN) when identifying students for gifted services. Next, we discuss how effective use of combining multiple criteria--including using two-phase identification systems--contributes to schools saving time and money while also better identifying students. To do this, we use newly introduced criteria for evaluating gifted and talented identification systems. Finally, we provide several keys for success that can help schools accomplish their identification goals effectively.

The purpose of this study was to examine factors associated with expectations regarding postsecondary education of students with autism spectrum disorder between the ages of 16 and 21 years. We conducted logistic regressions using variables at the student, family, and school levels using the National Longitudinal Transition Study 2012. Logistic regression results showed that parental expectations for attending college was the only significant predictor of students' own educational expectations. Students' adaptive functioning, autonomy levels, demographic and family variables, parent involvement, and prior roles in Individualized Education Program/transition planning were not significant predictors. Future research needs to examine how schools can develop effective ways to increase both students' and parents' expectations toward postsecondary education.

Universal screening is one of the most-common topics and well-accepted best practices within the field of gifted and talented education. There appears to be little disagreement that universally screening all students as part of a gifted and talented identification process results in fewer missed students. But surprisingly, there is little guidance on what makes for a quality universal screener--the tool that decides who needs further consideration. In this paper, we provide guidance that can help schools select the universal screener that helps them correctly identify as many students as possible at the lowest possible cost.

Using National Longitudinal Transition Study 2012 data, this study explored parent and youth expectations in the areas of postsecondary education, employment, independent living, and financial independence. Compared to youth with other disabilities, youth with intellectual and developmental disabilities and their parents had much lower expectations for the four postschool goals, and parent expectations were much lower than youth's own expectations. Also, youth's race, along with their daily living skills and functional abilities, were positively associated with parent and youth expectations in several future goal areas. Our discussion highlights implications for improving the transition experiences of youth with intellectual and developmental disabilities.

Zinc is integral to diverse biological functions, acting catalytically, structurally, and supportively in essential enzyme cycles, despite its limited amounts in the body. Targeting zinc enzymes with potent drugs, such as Vorinostat, demonstrates the therapeutic efficacy of zinc-binding ligands, notably in cutaneous T-cell lymphoma treatments. Our study merges experimental and theoretical approaches to analyze the coordination of 8-hydroxylquinoline (8HQ) inhibitors with biomimetic zinc complexes and human histone deacetylase 8 (HDAC8), a monozinc hydrolase enzyme. Assessing 10 8HQ derivatives for structural and electronic characteristics against these models, we observe minimal inhibition efficacy, corroborated through protein–ligand docking analyses, highlighting the complexities of inhibitor–zinc enzyme interactions and suggesting intricate noncovalent interactions that are important for ligand binding to enzymes not accounted for in model zinc hydrolase mimics.

Longwood Gardens (Kennett Square, PA, USA) is working toward a future where the beauty of nature can be enjoyed by all through its sustainability and stewardship efforts. Using case studies highlighting water quality and conservation, carbon footprint reduction, material circularity, and land stewardship, this paper examines the multifaceted approach that Longwood takes to address its environmental impact. First, a description of Longwood’s innovative water quality and conservation strategies and their integration of green and gray infrastructure is described. Next, the paper explores the comprehensive measures adopted to curtail its carbon footprint, from energy-efficient infrastructure to renewable energy sources. Then, Longwood’s commitment to material circularity is investigated, showcasing initiatives that reuse organic materials and create necessary products for the Gardens onsite. Finally, the Gardens’ holistic land stewardship practices are detailed, including habitat preservation and biodiversity enhancement. The paper concludes with valuable findings learned from the organization’s sustainability and stewardship journey, offering insights applicable to other gardens or campuses seeking to improve their ecological impact while maintaining a commitment to esthetic and horticultural excellence.

Abstract There is a large body of evidence that cellular metabolism governs inflammation, and that inflammation contributes to the progression of atherosclerosis. However, whether mitochondrial DNA synthesis affects macrophage function and atherosclerosis pathology is not fully understood. Here we show, by transcriptomic analyzes of plaque macrophages, spatial single cell transcriptomics of atherosclerotic plaques, and functional experiments, that mitochondrial DNA (mtDNA) synthesis in atherosclerotic plaque macrophages are triggered by vascular cell adhesion molecule 1 (VCAM-1) under inflammatory conditions in both humans and mice. Mechanistically, VCAM-1 activates C/EBPα, which binds to the promoters of key mitochondrial biogenesis genes - Cmpk2 and Pgc1a. Increased CMPK2 and PGC-1α expression triggers mtDNA synthesis, which activates STING-mediated inflammation. Consistently, atherosclerosis and inflammation are less severe in Apoe −/− mice lacking Vcam1 in macrophages. Downregulation of macrophage-specific VCAM-1 in vivo leads to decreased expression of LYZ1 and FCOR, involved in STING signalling. Finally, VCAM-1 expression in human carotid plaque macrophages correlates with necrotic core area, mitochondrial volume, and oxidative damage to DNA. Collectively, our study highlights the importance of macrophage VCAM-1 in inflammation and atherogenesis pathology and proposes a self-acerbating pathway involving increased mtDNA synthesis.

Abstract The interactions of environmental, geographic, socio-demographic, and epidemiological factors in shaping mosquito-borne disease transmission dynamics are complex and changeable, influencing the abundance and distribution of vectors and the pathogens they transmit. In this study, 27 years of cross-sectional malaria survey data (1990–2017) were used to examine the effects of these factors on Plasmodium falciparum and Plasmodium vivax malaria presence at the community level in Africa and Asia. Monthly long-term, open-source data for each factor were compiled and analyzed using generalized linear models and classification and regression trees. Both temperature and precipitation exhibited unimodal relationships with malaria, with a positive effect up to a point after which a negative effect was observed as temperature and precipitation increased. Overall decline in malaria from 2000 to 2012 was well captured by the models, as was the resurgence after that. The models also indicated higher malaria in regions with lower economic and development indicators. Malaria is driven by a combination of environmental, geographic, socioeconomic, and epidemiological factors, and in this study, we demonstrated two approaches to capturing this complexity of drivers within models. Identifying these key drivers, and describing their associations with malaria, provides key information to inform planning and prevention strategies and interventions to reduce malaria burden.

Abstract Background Pulmonary hypertension (PH) in dogs with myxomatous mitral valve disease (MMVD) is caused by increased pulmonary venous pressure. Thrombosis, vascular remodeling, and vasoconstriction mediated by platelets could exacerbate PH. Hypothesis Dogs with PH will exhibit a hypercoagulable state, characterized by increased platelet activation, platelet‐leukocyte, and platelet‐neutrophil aggregate formation. Animals Eleven dogs (≥3.5 kg) diagnosed with MMVD and PH and 10 dogs with MMVD lacking PH. Methods Prospective cohort ex vivo study. All dogs underwent echocardiographic examination, CBC, 3‐view thoracic radiographs, and heartworm antigen testing. Severity of PH and MMVD were assessed by echocardiography. Viscoelastic monitoring of coagulation was assessed using thromboelastography (TEG). Platelet activation and platelet‐leukocyte/platelet‐neutrophil interactions were assessed using flow cytometry. Plasma serotonin concentrations were measured by ELISA. Results Unstimulated platelets from dogs with MMVD and PH expressed more surface P‐selectin than MMVD controls (P = .03). Platelets from dogs with MMVD and PH had persistent activation in response to agonists. The number of platelet‐leukocyte aggregates was higher in dogs with MMVD and PH compared with MMVD controls (P = .01). Ex vivo stimulation of whole blood resulted in higher numbers of platelet‐neutrophil aggregates in dogs with MMVD and PH (P = .01). Assessment of hypercoagulability based on TEG or plasma serotonin concentrations did not differ between groups. Conclusion and Clinical Importance Platelet hyperresponsiveness and increased platelet‐neutrophil interaction occur in dogs with MMVD and PH, suggesting that platelets play a role of in the pathogenesis of PH. Clinical benefits of antiplatelet drugs in dogs with MMVD and PH require further investigation.

Abstract Achieving complete tumor resection is challenging and can be improved by real-time fluorescence-guided surgery with molecular-targeted probes. However, pre-clinical identification and validation of probes presents a lengthy process that is traditionally performed in animal models and further hampered by inter- and intra-tumoral heterogeneity in target expression. To screen multiple probes at patient scale, we developed a multispectral real-time 3D imaging platform that implements organoid technology to effectively model patient tumor heterogeneity and, importantly, healthy human tissue binding.

Abstract Phage predation is generally assumed to reduce microbial proliferation while not contributing to the spread of antibiotic resistance. However, this assumption does not consider the effect of phage predation on the spatial organization of different microbial populations. Here, we show that phage predation can increase the spread of plasmid-encoded antibiotic resistance during surface-associated microbial growth by reshaping spatial organization. Using two strains of the bacterium Escherichia coli, we demonstrate that phage predation slows the spatial segregation of the strains during growth. This increases the number of cell-cell contacts and the extent of conjugation-mediated plasmid transfer between them. The underlying mechanism is that phage predation shifts the location of fastest growth from the biomass periphery to the interior where cells are densely packed and aligned closer to parallel with each other. This creates straighter interfaces between the strains that are less likely to merge together during growth, consequently slowing the spatial segregation of the strains and enhancing plasmid transfer between them. Our results have implications for the design and application of phage therapy and reveal a mechanism for how microbial functions that are deleterious to human and environmental health can proliferate in the absence of positive selection.

IntroductionSocial support within Indigenous worldviews is recognized as a component of health and has been associated with physical activity and sedentary behaviour. Physical Activity (PA) is a modifiable behaviour that can help reduce risks of disease and benefit many dimensions of health. The purpose of this study was to compare the physical activity of Indigenous adults in Saskatchewan with and without family/friend support of PA.MethodsThe Family Influence on Physical Activity questionnaire was used to record the extent and forms of family/friend support of PA. The Godin Shepard Leisure Exercise Questionnaire (GSLEQ) was used to measure weekly PA, including moderate PA (MPA), vigorous PA (VPA), exercise frequency (WEF) and GSLEQ scores.ResultsIndigenous participants overall, First Nations and Cree participants specifically with family/friend involvement in PA reported greater weekly WEF and GSLEQ scores. Indigenous participants overall and First Nations participants specifically with family and friends who watch them engage in PA reported greater weekly VPA and GSLEQ scores. Among First Nations and Cree participants specifically, those with family/friends encouragement of PA reported greater weekly VPA, WEF and GSLEQ scores. Furthermore, First Nations participants with active family/friends reported significantly greater weekly VPA (36.8 ± 51.5 min·week−1 vs. 80.2 ± 108.5 min·week−1; p = 0.01). Greater weekly VPA was found in Métis participants with family/friend involvement in PA and with family/friends who watch them engage in PA (67.6 ± 59.6 min·week−1 vs. 29.5 ± 40.8 min·week−1; p = 0.01).DiscussionSocial support, specifically family/friends involvement, has a significant impact on Indigenous participation in PA.

BackgroundCrisis pregnancy centers (CPCs) are religious nonprofit organizations with a primary mission of diverting people from having abortions. One CPC tactic has been to locate near abortion facilities. Despite medical groups’ warnings that CPCs do not adhere to medical and ethical standards and pose risks, government support for CPCs has significantly increased. ObjectiveThis study aims to map CPCs, abortion facilities, and geographical areas in the United States into 4 zones based on their proximity to CPCs and abortion facilities. We sought to describe the number and percentage of reproductive-aged women living in each zone and the proximity of CPCs to abortion facilities. MethodsUsing 2021 data from CPC Map and the Advancing New Standards in Reproductive Health Abortion Facility Database, we determined the ratio of CPCs to abortion facilities. Along with census data, we categorized and mapped US block groups into 4 distinct zones based on locations of block group centroids within 15-mile (1 mile is approximately 1.609 km) radii of CPCs and abortion facilities, namely “no presence,” “CPC only,” “abortion facility only,” and “dual presence.” We calculated the number and percentage of block groups and reproductive-aged (15-49 years) women living in each zone. We calculated driving distances and drive times from abortion facilities to the nearest CPC and mapped abortion facilities with CPCs in close proximity. All analyses were conducted nationally and by region, division, and state. ResultsNationally, the ratio of CPCs to abortion facilities was 3.4, and 54.9% (131,410/239,462) of block groups were categorized in the “dual presence” zone, 26.6% (63,679/239,462) as “CPC only,” and 0.8% (63,679/239,462) as “abortion facility only.” Most reproductive-aged women (45,150,110/75,582,028, 59.7%) lived in a “dual presence” zone, 26.1% (19,696,572/75,582,028) in a “CPC only” zone, and 0.8% (625,403/75,582,028) in an “abortion facility only” zone. The number of block groups and women classified as living in each zone varied by region, division, and state. Nationally, the median distance from abortion facilities to the nearest CPC was 2 miles, and the median drive time was 5.5 minutes. Minimum drive times were

Summary: Microglia are strongly implicated in demyelinating neurodegenerative diseases with increasing evidence for roles in protection and healing, but the mechanisms that control CNS remyelination are poorly understood. Here, we show that microglia-specific deletion of tumor necrosis factor receptor 1 (TNFR1) and pharmacological inhibition of soluble TNF (solTNF) or downstream interleukin-1 receptor (IL-1R) allow maturation of highly activated disease-associated microglia with increased size and myelin phagocytosis capacity that accelerate cortical remyelination and motor recovery. Single-cell transcriptomic analysis of cortex at disease onset reveals that solTNF inhibition enhances reparative IL-10-responsive while preventing damaging IL-1-related signatures of disease-associated microglia. Longitudinal brain transcriptome analysis through disease reveals earlier recovery upon therapeutic loss of microglia TNFR1. The functional relevance of microglia inflammatory polarization pathways for disease is validated in vivo. Furthermore, disease-state microglia producing downstream IL-1/IL-18/caspase-11 targets are identified in human demyelinating lesions. Overall, redirecting disease microglia polarization by targeting cytokines is a potential approach for improving CNS repair in demyelinating disorders.

Radioligand therapies such as [177Lu] Lu-PSMA-617 have gained significant momentum in cancer treatment after clinical trials and multicenter studies demonstrated their safety and efficacy. As these innovative treatments become more widespread, rare and unique clinical manifestations are expected to be observed. In this report, we describe a case with metastatic castration-resistant prostate cancer (mCRPC) and peripancreatic lymph node metastases who developed acute pancreatitis following [177Lu] Lu-PSMA-617 therapy.

Aim: Diabetes and hypertension are major risk factors of cardiovascular disease, which is known to be the leading cause of global mortality in the world today. Studies have shown that the prevalence of these risk factors is on the rise, with the burden of diabetes alone increasing by 80% in the last two decades. Complications of diabetes and hypertension result in huge public health challenges for the country and catastrophic medical expenditures for families among the urban poor. Our study aims to estimate the prevalence of diabetes, hypertension, and other cardiovascular risk factors among adults in an urban underprivileged community of Bengaluru city. Objectives and Methods: A cross-sectional study was conducted over a period of 6 months where 2245 individuals aged 30 or older were interviewed using a structured interviewer-administered questionnaire used to capture sociodemographic details that assessed modifiable risk factors for diabetes and hypertension. Inclusion criteria for diabetes were considered if the random blood sugar reading was ≥200 mg/dL, whereas a diagnosis of hypertension was taken into consideration if the systolic blood pressure reading was ≥140 mmHg and/or diastolic blood pressure was ≥90 mmHg. Results: Among the 2245 participants that took part in the study, 15.5% were diabetics and 17.2% were hypertensive. There was a strong association of diabetes among consumers of alcohol, with more than one-third having a high prevalence of the disease (odds ratio (OR): 2.09, 95% confidence interval (95% CI): 1.1–3.9). More than half the population were consumers of junk food; the prevalence of diabetes in this group was 1.35 times higher than that in their counterparts (OR: 1.35, 95% CI: 1.0–1.8). A significant association of diabetes was also seen among those identified with central obesity (OR: 1.83, 95% CI: 1.4–2.5). One-third of the population who consumed alcohol were found to be diagnosed with hypertension (OR: 3.08, 95% CI: 1.6–5.9), and one-fifth of individuals who were regular consumers of junk food had a higher prevalence of hypertension (OR: 1.41, 95% CI: 1.1–1.8). A higher prevalence of hypertension was also seen among individuals with central obesity or a body mass index (BMI) of >30 (OR: 1.59, 95% CI: 1.2–2.1; OR: 1.92, 95% CI: 1.4–2.6). Conclusion: The findings from our study conducted in an urban underprivileged area of Bengaluru city shed light on the significant associations between diabetes and hypertension and various demographic and lifestyle factors. Specifically, male gender and lower educational status were found to have a significant association with diabetes, whereas being unmarried and having a high BMI status were strongly linked to hypertension. In addition, the study revealed that elderly individuals, alcohol consumers, junk food eaters, and those with central obesity demonstrated an increased risk for both diabetes and hypertension. By identifying these risk factors, targeted interventions can be developed to address the unique challenges faced by this vulnerable section of society. Strategies can be designed to raise awareness, encourage healthier lifestyle choices, and improve access to healthcare services to effectively prevent and manage diabetes and hypertension in this community.

Abstract Background Lymphangioleiomyomatosis (LAM) is common in tuberous sclerosis complex (TSC) yet under recognised with management mostly based upon evidence obtained from patients with sporadic LAM. We performed a prospective audit of patients with TSC-LAM attending a national referral centre to inform management guidelines. Methods The UK LAM Centre was established in 2011 and conducts a prospective audit of pre-defined quality outcomes for all subjects. Audit data are reported on all patients with TSC-LAM and a comparator population of patients with sporadic LAM. Results Between 2011 and 2022, 73 patients were seen with TSC-LAM. All were women with a mean (SD) age of 39 (12) years. Referral rates were similar over the study period including after the introduction of CT screening. Median age of diagnosis with TSC was 11 years (range 0–70) with one third diagnosed with TSC as adults. Compared with all TSC patients in the ‘TOSCA’ registry, TSC-LAM patients tended to have been diagnosed with TSC at an older age, had fewer neuro-cognitive manifestations and were more likely to have angiomyolipoma. The most common presentations of TSC-LAM were following workup for angiomyolipoma, pneumothorax or dyspnoea with only one fifth detected after CT screening. Baseline FEV1 and DLCO at first assessment were reduced to 77 and 63% predicted respectively and were similar to patients with sporadic LAM. During follow-up, FEV1 fell by a mean of 81 ml/year and DLCO fell by 0.309 mmol/ml/kPa/year in patients not being treated with an mTOR inhibitor. 55% required treatment with either sirolimus or Everolimus for LAM or angiomyolipoma respectively. For those treated with an mTOR inhibitor, mean FEV1 fell by 3 ml/year and DLCO increased by 0.032 mmol/ml/kPa/year and was similar to sporadic LAM. Risk of death due to LAM or need for lung transplant in patients with TSC-LAM was 0.67%/year. Conclusions Despite screening recommendations, LAM is often diagnosed in TSC after symptoms develop which may delay treatment. Complications including pneumothorax and loss of lung function are significant and similar to sporadic LAM. Work is needed to implement the recommended CT screening for LAM and improve respiratory care for TSC-LAM.

Abstract The Perseverance rover has collected seven oriented samples of sedimentary rocks, all likely older than the oldest signs of widespread life on Earth, at the exposed base of the western fan in Jezero crater, Mars. The samples include a sulfate‐ and clay‐bearing mudstone and sandstone, a fluvial sandstone from a stratigraphically low position at the fan front, and a carbonate‐bearing sandstone deposited above the sulfate‐bearing strata. All samples contain aqueously precipitated materials and most or all were aqueously deposited. Although the rover instruments have not confidently detected organic matter in the rocks from the fan front, the much more sensitive terrestrial instruments will still be able to search for remnants of prebiotic chemistries and past life, and study Mars's past habitability in the samples returned to Earth. The hydrated, sulfate‐bearing mudstone has the highest potential to preserve organic matter and biosignatures, whereas the carbonate‐bearing sandstones can be used to constrain when and for how long Jezero crater contained liquid water. Returned sample science analyses of sulfate, carbonate, clay, phosphate and igneous minerals as well as trace metals and volatiles that are present in the samples acquired at the fan front would provide transformative insights into past habitable environments on Mars, the evolution of its magnetic field, atmosphere and climate and the past and present cycling of atmospheric and crustal water, sulfur and carbon.

Adaptive management, a process of planning, implementing, and evaluating management strategies, is often recommended for monitoring ecological systems. However, few examples of successful implementation and retrospective case studies exist. We provide a case study of adaptively managing hatchery-assisted protection and recovery for Chinook salmon (Oncorhynchus tshawytscha) and winter steelhead trout (O. mykiss) during and after the removal of two large mainstem dams in the Elwha River, WA. We summarize key aspects of the monitoring and adaptive management plan over the last decade and highlight successes, challenges, and complications during the plan’s implementation. The Elwha Monitoring and Adaptive Management Guidelines included a trigger-based system for moving through four phases of recovery that included preservation, recolonization, local adaptation, and viable natural population, each with differing levels of hatchery production as the management actions. The monitoring component of the plan has been very successful, providing critical data to guide management actions that otherwise may not have occurred and, opportunistically, provided data for other native species in the Elwha River. Implementing adaptive management provided mixed results and was at times hindered by divergent management goals among project partners, the inflexibility of the Endangered Species Act regulatory requirements as implemented for this project, and conflicting information among guidance documents. We learned that some metrics and triggers in the plan were ill-defined or too difficult to measure in the field. In some cases, the performance indicators and/or triggers were successfully modified to incorporate what was learned; however, in other cases, we were unable to revise the values due to differing opinions among partners. The ability to reach consensus on revised triggers appeared to be influenced by the recovery trajectory of the species involved. The implemented adaptive management strategy resulted in substantial collaboration and learning, which resulted in revised management strategies, but was imperfect. Sufficient long-term funding is necessary to implement a well-designed monitoring program and could benefit from including a defined leadership position to shepherd and facilitate a multi-stakeholder adaptive management program. Additionally, incorporating adaptive management into legally binding conditions under the Endangered Species Act is feasible, but requires substantial pre-planning in close coordination with regulatory agencies.

BackgroundMany patients use artificial intelligence (AI) chatbots as a rapid source of health information. This raises important questions about the reliability and effectiveness of AI chatbots in delivering accurate and understandable information.PurposeTo evaluate and compare the accuracy, conciseness, and readability of responses from OpenAI ChatGPT-4 and Google Bard to patient inquiries concerning the novel 177Lu-PSMA-617 therapy for prostate cancer.Materials and methodsTwo experts listed the 12 most commonly asked questions by patients on 177Lu-PSMA-617 therapy. These twelve questions were prompted to OpenAI ChatGPT-4 and Google Bard. AI-generated responses were distributed using an online survey platform (Qualtrics) and blindly rated by eight experts. The performances of the AI chatbots were evaluated and compared across three domains: accuracy, conciseness, and readability. Additionally, potential safety concerns associated with AI-generated answers were also examined. The Mann-Whitney U and chi-square tests were utilized to compare the performances of AI chatbots.ResultsEight experts participated in the survey, evaluating 12 AI-generated responses across the three domains of accuracy, conciseness, and readability, resulting in 96 assessments (12 responses x 8 experts) for each domain per chatbot. ChatGPT-4 provided more accurate answers than Bard (2.95 ± 0.671 vs 2.73 ± 0.732, p=0.027). Bard’s responses had better readability than ChatGPT-4 (2.79 ± 0.408 vs 2.94 ± 0.243, p=0.003). Both ChatGPT-4 and Bard achieved comparable conciseness scores (3.14 ± 0.659 vs 3.11 ± 0.679, p=0.798). Experts categorized the AI-generated responses as incorrect or partially correct at a rate of 16.6% for ChatGPT-4 and 29.1% for Bard. Bard’s answers contained significantly more misleading information than those of ChatGPT-4 (p = 0.039).ConclusionAI chatbots have gained significant attention, and their performance is continuously improving. Nonetheless, these technologies still need further improvements to be considered reliable and credible sources for patients seeking medical information on 177Lu-PSMA-617 therapy.

ABSTRACT Chlamydia trachomatis is the leading cause of bacterial sexually transmitted infections in the USA and of preventable blindness worldwide. This obligate intracellular pathogen replicates within a membrane-bound inclusion, but how it acquires nutrients from the host while avoiding detection by the innate immune system is incompletely understood. C. trachomatis accomplishes this in part through the translocation of a unique set of effectors into the inclusion membrane, the inclusion membrane proteins (Incs). Incs are ideally positioned at the host-pathogen interface to reprogram host signaling by redirecting proteins or organelles to the inclusion. Using a combination of co-affinity purification, immunofluorescence confocal imaging, and proteomics, we characterize the interaction between an early-expressed Inc of unknown function, Tri1, and tumor necrosis factor receptor-associated factor 7 (TRAF7). TRAF7 is a multi-domain protein with a RING finger ubiquitin ligase domain and a C-terminal WD40 domain. TRAF7 regulates several innate immune signaling pathways associated with C. trachomatis infection and is mutated in a subset of tumors. We demonstrate that Tri1 and TRAF7 specifically interact during infection and that TRAF7 is recruited to the inclusion. We further show that the predicted coiled-coil domain of Tri1 is necessary to interact with the TRAF7 WD40 domain. Finally, we demonstrate that Tri1 displaces the native TRAF7 binding partners, mitogen-activated protein kinase kinase kinase 2 (MEKK2), and MEKK3. Together, our results suggest that by displacing TRAF7 native binding partners, Tri1 has the capacity to alter TRAF7 signaling during C. trachomatis infection.IMPORTANCEChlamydia trachomatis is the leading cause of bacterial sexually transmitted infections in the USA and preventable blindness worldwide. Although easily treated with antibiotics, the vast majority of infections are asymptomatic and therefore go untreated, leading to infertility and blindness. This obligate intracellular pathogen evades the immune response, which contributes to these outcomes. Here, we characterize the interaction between a C. trachomatis-secreted effector, Tri1, and a host protein involved in innate immune signaling, TRAF7. We identified host proteins that bind to TRAF7 and demonstrated that Tri1 can displace these proteins upon binding to TRAF7. Remarkably, the region of TRAF7 to which these host proteins bind is often mutated in a subset of human tumors. Our work suggests a mechanism by which Tri1 may alter TRAF7 signaling and has implications not only in the pathogenesis of C. trachomatis infections but also in understanding the role of TRAF7 in cancer.

Fire is a key disturbance process that shapes the structure and function of montane temperate rainforest in the Pacific Northwest (PNW). Recent research is revealing more frequent historical fire activity in the western central Cascades than expected by conventional theory. Indigenous peoples have lived in the PNW for millennia. However, Indigenous people's roles in shaping vegetation mosaics in montane temperate forests of the PNW has been overlooked, despite archaeological evidence of long-term, continuous human use of these landscapes. In this paper, we present a generalizable research framework for overcoming biases often inherent in historical fire research. The framework centers Indigenous perspectives and ethnohistory, leveraging theory in human ecology and archaeology to interpret fire histories. We apply this framework to place-based, empirical evidence of Indigenous land use and dendroecological fire history. Our framework leads us to conclude that the most parsimonious explanation for the occurrence of historical high fire frequency in the western Cascades is Indigenous fire stewardship. Further, our case study makes apparent that scholars can no longer ignore the role of Indigenous people in driving montane forest dynamics in the PNW.

IntroductionExtraintestinal Escherichia coli infections represent a growing public health threat, However, current studies often overlook important factors such as temporal patterns of infection, phylogenetic and clonal background, or the host gut E. coli population, despite their likely significance.MethodsIn this study, we analyzed >7000 clinical E. coli isolates from patients at the Minneapolis Veterans Affairs Health Care System (2012–2019), and concurrent fecal E. coli from uninfected veterans. We assessed phylogenetic group distribution, membership in selected sequence types (STs), and subsets thereof—including the pandemic, resistance-associated ST131-H30R, and ST1193 lineages—and strain type, as defined by pulsed-field gel electrophoresis. We then analyzed these features alongside the temporal patterns of infection in individual hosts.ResultsThe H30R lineage emerged as the leading lineage, both overall and among fluoroquinolone-resistant isolates, with ST1193 following among fluoroquinolone-resistant isolates. Recurrences were common, occurring in 31% of subjects and 41% of episodes, and often multiple and delayed/prolonged (up to 23 episodes per subject; up to 2655d post-index). Remarkably, these recurrences typically involved the subject’s index strain (63% of recurrences), even when affecting extra-urinary sites. ST131, H30R, ST1193, and fluoroquinolone-resistant strains generally caused significantly more recurrences than did other strains, despite similar recurrence intervals. ST131 strain types shifted significantly over the study period. Infection-causing strains were commonly detectable in host feces at times other than during an infection episode; the likelihood of detection varied with surveillance intensity and proximity to the infection. H30R and ST1193 were prominent causes of fecal-clinical clonal overlap.DiscussionThese findings provide novel insights into the temporal and clonal characteristics of E. coli infections in veterans and support efforts to develop anti-colonization interventions.

Summary: The amnion is a thin layer of fetal origin in contact with the amniotic fluid which plays a key role at the feto-maternal interface during pregnancy. Here, we present a protocol for isolation of human and Rhesus macaque amnion cells. We describe steps for tissue dissection, cell isolation for flow cytometry analysis, and RNA isolation for RNA sequencing library preparation and analysis. This protocol can provide insights into altered immunological pathways during intrauterine infections to develop new therapeutic strategies.For complete details on the use and execution of this protocol, please refer to Presicce et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract Post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS) is a disabling disorder, yet the clinical phenotype is poorly defined, the pathophysiology is unknown, and no disease-modifying treatments are available. We used rigorous criteria to recruit PI-ME/CFS participants with matched controls to conduct deep phenotyping. Among the many physical and cognitive complaints, one defining feature of PI-ME/CFS was an alteration of effort preference, rather than physical or central fatigue, due to dysfunction of integrative brain regions potentially associated with central catechol pathway dysregulation, with consequences on autonomic functioning and physical conditioning. Immune profiling suggested chronic antigenic stimulation with increase in naïve and decrease in switched memory B-cells. Alterations in gene expression profiles of peripheral blood mononuclear cells and metabolic pathways were consistent with cellular phenotypic studies and demonstrated differences according to sex. Together these clinical abnormalities and biomarker differences provide unique insight into the underlying pathophysiology of PI-ME/CFS, which may guide future intervention.

Background and Aims: The dual sugar absorption test as a classic measure of human intestinal permeability has limited clinical utility due to lengthy and cumbersome urine collection, assay variability, and long turnaround. We aimed to determine if the orally administered fluorophore MB-102 (relmapirazin) (molecular weight [MW] = 372) compares to lactulose (L) (MW = 342) and rhamnose (R) (MW = 164)-based dual sugar absorption test as a measure of gut permeability in people with a spectrum of permeability including those with Crohn’s disease (CD). Methods: We performed a single-center, randomized, open-label, crossover study comparing orally administered MB-102 (1.5 or 3.0 mg/kg) to L (1000 mg) and R (200 mg). Adults with active small bowel CD on magnetic resonance enterography (cases) and healthy adults (controls) were randomized to receive either MB-102 or L and R on study day 1, and the other tracer 3 to 7 days later. Urine was collected at baseline and 1, 2, 4, 6, 8, 10, and 12 hours after tracer ingestion to calculate the cumulative urinary percent excretion of MB-102 and L and R. Results: Nine cases and 10 controls completed the study without serious adverse events. Urinary recovery of administered MB-102 correlated with recovery of lactulose (r-squared = 0.83) for all participants. MB-102 urine recovery was also tracked with the L:R ratio urine recovery (r-squared = 0.57). In controls, the percentages of L and MB-102 recovered were similar within a narrow range, unlike in CD patients. Conclusion: This first-in-human study of an orally administered fluorophore to quantify gastrointestinal permeability in adults with CD demonstrates that MB-102 is well tolerated, and its recovery in urine mirrors that of percent L and the L:R ratio.