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Strontium isotope (87Sr/86Sr) analysis with reference to strontium isotope landscapes (Sr isoscapes) allows reconstructing mobility and migration in archaeology, ecology, and forensics. However, despite the vast potential of research involving 87Sr/86Sr analysis particularly in Africa, Sr isoscapes remain unavailable for the largest parts of the continent. Here, we measure the 87Sr/86Sr ratios in 778 environmental samples from 24 African countries and combine this data with published data to model a bioavailable Sr isoscape for sub-Saharan Africa using random forest regression. We demonstrate the efficacy of this Sr isoscape, in combination with other lines of evidence, to trace the African roots of individuals from historic slavery contexts, particularly those with highly radiogenic 87Sr/86Sr ratios uncommon in the African Diaspora. Our study provides an extensive African 87Sr/86Sr dataset which includes scientifically marginalized regions of Africa, with significant implications for the archaeology of the transatlantic slave trade, wildlife ecology, conservation, and forensics.

Objectives: Community sites, including schools, are important settings for interventions to promote children and young people's mental health and wellbeing. A central provision to support mental health in the UK is school- and community-based counselling services. However, the evidence-base for school counselling services is limited by weak evaluation designs, lack of understanding of different counselling approaches in use, and a failure to conceptualise counselling services as part of a wider complex system. To address the last point, this article takes a complex system-focused perspective to explore how a 'system disruption', that is counselling service implementation, can be optimised in the Welsh education system. Design: The approach used in this study is a mixed-method qualitative design. Setting: Participants were recruited from school and community settings. They included children and young people, parents, carers, school staff, counsellors and stakeholders from health and education. Method: Consultations, key system stakeholder interviews and school case studies were conducted. All stakeholders were asked about their experiences of local authority-funded school- and community-based counselling services in Wales. Interview and consultation data were analysed using a thematic analysis approach. Results: Data converged into three main themes focusing on the specifics of counselling sessions, counselling services as part of universal mental health provision and a whole education system approach. These three themes are brought together into a complex systems-focused model of an optimised school- and community-based counselling service. Conclusion: The model offers an opportunity to address issues with current counselling services in Wales and improve outcomes and sustainability by increasing the likelihood they will become embedded in the whole education system.

In May and June of 2021, marine microbial samples were collected for DNA sequencing in East Sound, WA, USA every 4 hours for 22 days. This high temporal resolution sampling effort captured the last 3 days of a Rhizosolenia sp. bloom, the initiation and complete bloom cycle of Chaetoceros socialis (8 days), and the following bacterial bloom (2 days). Metagenomes were completed on the time series, and the dataset includes 128 size-fractionated microbial samples (0.22-1.2 μm), providing gene abundances for the dominant members of bacteria, archaea, and viruses. This dataset also has time-matched nutrient analyses, flow cytometry data, and physical parameters of the environment at a single point of sampling within a coastal ecosystem that experiences regular bloom events, facilitating a range of modeling efforts that can be leveraged to understand microbial community structure and their influences on the growth, maintenance, and senescence of phytoplankton blooms.

Cash transfer policies have been widely discussed as mechanisms to curb intergenerational transmission of socioeconomic disadvantage. In this paper, we take advantage of a large casino-funded family transfer program introduced in a Southeastern American Indian Tribe to generate difference-in-difference estimates of the link between childrens cash transfer exposure and third grade math and reading test scores of their offspring. Here we show greater math (0.25 standard deviation [SD], p =.0148, 95% Confidence Interval [CI]: 0.05, 0.45) and reading (0.28 SD, p = .0066, 95% CI: 0.08, 0.49) scores among American Indian students whose mother was exposed ten years longer than other American Indian students to the cash transfer during her childhood (or relative to the non-American Indian student referent group). Exploratory analyses find that a mothers decision to pursue higher education and delay fertility appears to explain some, but not all, of the relation between cash transfers and childrens test scores. In this rural population, large cash transfers have the potential to reduce intergenerational cycles of poverty-related educational outcomes.

Clonal hematopoiesis (CH) is an age-associated phenomenon leading to an increased risk of both hematologic malignancy and nonmalignant organ dysfunction. Increasingly available genetic testing has made the incidental discovery of CH clinically common yet evidence-based guidelines and effective management strategies to prevent adverse CH health outcomes are lacking. To address this gap, the prospective CHIVE (clonal hematopoiesis and inflammation in the vasculature) registry and biorepository was created to identify and monitor individuals at risk, support multidisciplinary CH clinics, and refine taxonomy and standards of practice for CH risk mitigation. Data from the first 181 patients enrolled in this prospective registry recapitulate the molecular epidemiology of CH from biobank-scale retrospective studies, with DNMT3A, TET2, ASXL1, and TP53 as the most commonly mutated genes. Blood counts across all hematopoietic lineages trended lower in patients with CH. In addition, patients with CH had higher rates of end organ dysfunction, in particular chronic kidney disease. Among patients with CH, variant allele frequency was independently associated with the presence of cytopenias and progression to hematologic malignancy, whereas other common high-risk CH clone features were not clear. Notably, accumulation of multiple distinct high-risk clone features was also associated with cytopenias and hematologic malignancy progression, supporting a recently published CH risk score. Surprisingly, ∼30% of patients enrolled in CHIVE from CH clinics were adjudicated as not having clonal hematopoiesis of indeterminate potential, highlighting the need for molecular standards and purpose-built assays in this field. Maintenance of this well-annotated cohort and continued expansion of CHIVE to multiple institutions are underway and will be critical to understanding how to thoughtfully care for this patient population.

We present a novel small molecule antiviral chemotype that was identified by an unconventional cell-free protein synthesis and assembly-based phenotypic screen for modulation of viral capsid assembly. Activity of PAV-431, a representative compound from the series, has been validated against infectious viruses in multiple cell culture models for all six families of viruses causing most respiratory diseases in humans. In animals, this chemotype has been demonstrated efficacious for porcine epidemic diarrhoea virus (a coronavirus) and respiratory syncytial virus (a paramyxovirus). PAV-431 is shown to bind to the protein 14-3-3, a known allosteric modulator. However, it only appears to target the small subset of 14-3-3 which is present in a dynamic multi-protein complex whose components include proteins implicated in viral life cycles and in innate immunity. The composition of this target multi-protein complex appears to be modified upon viral infection and largely restored by PAV-431 treatment. An advanced analog, PAV-104, is shown to be selective for the virally modified target, thereby avoiding host toxicity. Our findings suggest a new paradigm for understanding, and drugging, the host-virus interface, which leads to a new clinical therapeutic strategy for treatment of respiratory viral disease.

Autism spectrum disorder (ASD) is a neuropsychiatric condition that may be associated with negative health outcomes. This retrospective cohort study reveals the odds of hospitalization and mortality based on ASD for a population of insured patients with COVID-19. The odds of hospitalization and mortality for people with ASD were found to be greater than individuals without ASD when adjusted for sociodemographic characteristics. Hospitalization and mortality was associated with a dose-response increase to comorbidity counts (1 to 5+). Odds of mortality remained greater for those with ASD when adjusting for comorbid health conditions. ASD is a risk factor for COVID-19 mortality. Comorbid health conditions play a particular role in increasing the odds of COVID-19 related hospitalization and death for ASD patients.

Friendships can be generally defined as relationships that foster affection and interdependence between individuals, and they can play an essential role in individuals' mental health and well-being (Laursen et al., [...], Friendships between heteros exual men and gay, bisexual, and other men who have sex with men (gbMSM) appear to be less common than other friendship dyads. While some heterosexual men's fear of being perceived as gay may act as a barrier in forming these friendships, research conducted within the past decade suggests that attitudes toward gbMSM are improving in Western cultures. Little is known regarding how heterosexual men react to their peers who are gbMSM after disclosing their sexual orientations to them during this cultural shift in North America. Using inclusive masculinity theory as a framework, the purpos e was to examine how friendships between heterosexual men and gbMSM are impacted following their coming out experiences. Data were collected from heterosexual men and gbMSM aged 18-36 (M = 28.52) residing in the United States and Canada (N = 443) through Amazon Mechanical Turk. Heteros exual and gbMSM were asked to answer open-ended questions regarding the gbMSM's coming out experiences and describe changes in their friendships afterward. Thematic analysis guidelines were followed to analyze the responses. Results indicated three pathways for friendships: a positive coming-out experience with an improved friendship, a neutral coming-out experience with no change in the friendship, and a negative experience followed by a damaged or terminated friends hip. Findings suggest that positive attitudes toward cross -orientation friendships may be more prevalent and accepted at present than historically. These findings start an important dialogue with the potential implication of further normalizing positive friends hips between heterosexual men and gbMSM. KEYWORDS: Cross -orientation friendships, gay men, heterosexual men, qualitative research

Soil fungi belonging to different functional guilds, such as saprotrophs, pathogens, and mycorrhizal symbionts, play key roles in forest ecosystems. To date, no study has compared the actual gene expression of these guilds in different forest soils. We used metatranscriptomics to study the competition for organic resources by these fungal groups in boreal, temperate, and Mediterranean forest soils. Using a dedicated mRNA annotation pipeline combined with the JGI MycoCosm database, we compared the transcripts of these three fungal guilds, targeting enzymes involved in C- and N mobilization from plant and microbial cell walls. Genes encoding enzymes involved in the degradation of plant cell walls were expressed at a higher level in saprotrophic fungi than in ectomycorrhizal and pathogenic fungi. However, ectomycorrhizal and saprotrophic fungi showed similarly high expression levels of genes encoding enzymes involved in fungal cell wall degradation. Transcripts for N-related transporters were more highly expressed in ectomycorrhizal fungi than in other groups. We showed that ectomycorrhizal and saprotrophic fungi compete for N in soil organic matter, suggesting that their interactions could decelerate C cycling. Metatranscriptomics provides a unique tool to test controversial ecological hypotheses and to better understand the underlying ecological processes involved in soil functioning and carbon stabilization.

BACKGROUND: Residence in rural areas is often a barrier to health care access. To date, differences in access to kidney transplantation among children who reside in rural and micropolitan areas of the US have not been explored. METHODS: A retrospective cohort study of children

Much literature in the US documents an intergenerational transmission of birthing person and perinatal morbidity in socioeconomically disadvantaged groups. A separate line of work indicates that family cash transfers may improve life chances of low-income families well into adulthood. By exploiting a quasi-random natural experiment of a large family cash transfer among a southeastern American Indian (AI) tribe in rural North Carolina, we examine whether a perturbation in socioeconomic status during childhood improves birthing person/perinatal outcomes when they become parents themselves. We acquired birth records on 6805 AI and non-AI infants born from 1995 to 2018. Regression methods to examine effect modification tested whether the birthing persons American Indian (AI) status and exposure to the family cash transfer during their childhood years corresponds with improvements in birthing person and perinatal outcomes. Findings show an increase in age at childbearing (coef: 0.15 years, 95% confidence interval [CI]: 0.05, 0.25) and a decrease in pre-pregnancy body mass index (BMI; coef: -0.42, 95% CI: -0.76, -0.09) with increased duration of cash transfer exposure during childhood. The odds of large-for-gestational age at delivery, as well as mean infant birthweight, is also reduced among AI births whose birthing person had relatively longer duration of exposure to the cash transfer. We, however, observe no relation with other birthing person/perinatal outcomes (e.g., tobacco use during pregnancy, preterm birth). In this rural AI population, cash transfers in one generation correspond with improved birthing person and infant health in the next generation.

Abstract A collection of datasets describing six years of experiments on maize (Zea mays, L.) (corn) is presented (1989, 1990, 1994, 2013, 2016, and 2018). Four weighing lysimeters were used to determine crop evapotranspiration (ET). In-soil and above ground microclimate and ET data are presented on a 15-minute interval as are weather data for all days of the year. Data analysis determined ET, precipitation, irrigation, and dew and frost accumulation on a 15-minute basis from lysimeter mass data. Soil water content data from calibrated neutron probe readings is presented on a periodic basis. Crop planting, harvest, fertilization, pest control, and other agronomic information are presented in agronomic calendars by day of year. Crop growth data are presented on a periodic basis throughout the growing season, as are final crop biomass and yield data. The data are suitable for analysis of effects of irrigation and other agronomic decisions on crop yield and water productivity in the Southern High Plains region of the USA, for model calibration and testing, and for model improvement.

As part of a Patient-Centered Outcomes Research Institute (PCORI) Eugene Washington Engagement Award aimed at improving capacity to address maternal mental health in research, this collection of eight stories describes the unique experiences from caregivers (N = 2), patient/caregiver dyads (N = 2), healthcare stakeholders (N = 2), and community stakeholders (N = 2). Shared here are narratives dedicated to uplifting and supporting maternal mental health through storytelling. Elevating the voices and lived experiences of these diverse perspectives helps one understand the deeper and sometimes “invisible” needs of birthing people, thus moving beyond the status quo.

Abstract Background Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a range of histological findings from the generally benign simple steatosis to steatohepatitis (MASH) which can progress to fibrosis and cirrhosis. Several factors, including the microbiome, may contribute to disease progression. Results Here, we demonstrate links between the presence and abundance of specific bacteria in the adipose and liver tissues, inflammatory genes, immune cell responses, and disease severity. Overall, in MASLD patients, we observed a generalized obesity-induced translocation of gut bacteria to hepatic and adipose tissues. We identified microbial patterns unique to more severely diseased tissues. Specifically, Enterococcus, Granulicatella, and Morganellaceae abundance is positively correlated with immune cell counts and inflammatory gene expression levels, and both genera are significantly enriched in MASH patients. Brevibacterium is enriched in adipose tissues of patients with liver fibrosis. Conclusion Together, these results provide further insight into the microbial factors that may be driving disease severity. Video Abstract

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

Physical accessibility at colleges and universities is a perennial and challenging issue. Some campuses have made efforts to address these challenges through a variety of advocacy initiatives, while others have used disability simulations to bring greater awareness of physical accessibility to campus communities. An alternative approach to disability simulations and other accessibility awareness exercises is the Accessibility Expedition (AE). The AE engages participants in an exploration of campus spaces facilitated by disabled individuals and individuals knowledgeable of ADA Standards for Accessible Design and/or universal design (UD). The exploration is followed by a debriefing session to discuss barriers to equitable participation, as well as evidence of accessible or universal design practices. The description, rationale, steps for implementation, and observed outcomes of the AE practice are discussed.

Selenoproteins are a unique class of proteins that contain the 21st amino acid, selenocysteine (Sec). Addition of Sec into a protein is achieved by recoding of the UGA stop codon. All 25 mammalian selenoprotein mRNAs possess a 3′ UTR stem-loop structure, the Selenocysteine Insertion Sequence (SECIS), which is required for Sec incorporation. It is widely believed that the SECIS is the major RNA element that controls Sec insertion, however recent findings in our lab suggest otherwise for Selenoprotein S (SelS). Here we report that the first 91 nucleotides of the SelS 3′ UTR contain a proximal stem loop (PSL) and a conserved sequence we have named the SelS Positive UGA Recoding (SPUR) element. We developed a SelS-V5/UGA surrogate assay for UGA recoding, which was validated by mass spectrometry to be an accurate measure of Sec incorporation in cells. Using this assay, we show that point mutations in the SPUR element greatly reduce recoding in the reporter; thus, the SPUR is required for readthrough of the UGA-Sec codon. In contrast, deletion of the PSL increased Sec incorporation. This effect was reversed when the PSL was replaced with other stem-loops or an unstructured sequence, suggesting that the PSL does not play an active role in Sec insertion. Additional studies revealed that the position of the SPUR relative to the UGA-Sec codon is important for optimal UGA recoding. Our identification of the SPUR element in the SelS 3′ UTR reveals a more complex regulation of Sec incorporation than previously realized.

Currently, the prevalence of autism spectrum disorder (henceforth "autism") is 1 in 36, an increasing trend from previous estimates. In 2015, the United States adopted a new version (International Classification of Diseases, 10th Revision) of the World Health Organization coding system, a standard for classifying medical conditions. Our goal was to examine how the transition to this new coding system impacted autism diagnoses in 10 healthcare systems. We obtained information from electronic medical records and insurance claims data from July 2014 through December 2016 for each healthcare system. We used member enrollment data for 30 consecutive months to observe changes 15 months before and after adoption of the new coding system. Overall, the rates of autism per 1000 enrolled members was increasing for 0- to 5-year-olds before transition to International Classification of Diseases, 10th Revision and did not substantively change after the new coding was in place. There was variation observed in autism diagnoses before and after transition to International Classification of Diseases, 10th Revision for other age groups. The change to the new coding system did not meaningfully affect autism rates at the participating healthcare systems. The increase observed among 0- to 5-year-olds is likely indicative of an ongoing trend related to increases in screening for autism rather than a shift associated with the new coding.

Recommendations for achieving generalized instructional outcomes often overlook the capacity for generative learning for most verbally competent humans. Four children (ages 5-8) participated in this project. In Study 1, we provided decontextualized discrete trial teaching to establish arbitrary relations between colors, pictures of characters, and researcher motor actions. All participants engaged in derivative responding, providing evidence of relational framing. Subsequently, we demonstrated that, with no additional instruction, these derivatives contributed to effective action within a socially valid context (i.e., Candyland gameplay). Study 2 extended the demonstration by teaching frames of opposition. Following teaching, all participants engaged in novel and contextually appropriate responding that entailed the derivation of both coordination and opposition between untrained stimuli. This outcome demonstrates how teaching simple relations can result in learning that manifests at higher levels of complexity (i.e., relational networking), providing some evidence that there can be socially valid benefits to decontextualized discrete trial instruction.