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Background: The National Federation of State High School Associations provides recommendations regarding health and safety policies; however, policy development is governed at the state level. Given interstate differences in governance, the primary purpose was to describe processes that State High School Athletic Associations (SHSAAs) utilize to develop a new policy. The secondary objective was to determine what methods associations use to implement new policies. Methods: A cross-sectional survey requested SHSAA (n = 51) representatives to report how athlete health and safety policies are introduced, revised, approved, and implemented within their state. The 22-question survey was developed to gather variables for the aims of the study. Descriptive statistics were calculated for each survey item. Results: Of states who responded (n = 33), most reported a 2-committee (n = 24, 72.7%) process for developing and vetting policies, with initiation from the Sports Medicine Advisory Committee (n = 27, 81.8%), followed by an executive-level committee (n = 18, 66.7%). States reported total time from policy initiation to final approval ranged from 2 weeks to over 12 months. When a new policy was approved, most states indicated implementation began with an e-mail (n = 24, 72.7%) sent to Athletic Directors (n = 26, 78.8%). School principal or district superintendent were reported as the position in charge of compliance (36.4%, n = 12). Conclusions: Most SHSAAs use a 2-step process to write and review an athlete health and safety policy before approval. SHSAAs that require a longer policy development time could delay the implementation of important health measures. SHSAAs could consider additional communication methods to ensure information reaches all stakeholders.

Abstract TRIM32 is a E3 ubiquitin -ligase containing RING, B-box, coiled-coil and six C-terminal NHL domains. Mutations involving NHL and coiled-coil domains result in a pure myopathy (LGMD2H/STM) while the only described mutation in the B-box domain is associated with a multisystemic disorder without myopathy (Bardet-Biedl syndrome type11), suggesting that these domains are involved in distinct processes. Knock-out (T32KO) and knock-in mice carrying the c.1465G > A (p.D489N) involving the NHL domain (T32KI) show alterations in muscle regrowth after atrophy and satellite cells senescence. Here, we present phenotypical description and functional characterization of mutations in the RING, coiled-coil and NHL domains of TRIM32 causing a muscle dystrophy. Reduced levels of TRIM32 protein was observed in all patient muscle studied, regardless of the type of mutation (missense, single amino acid deletion, and frameshift) or the mutated domain. The affected patients presented with variable phenotypes but predominantly proximal weakness. Two patients had symptoms of both muscular dystrophy and Bardet-Biedl syndrome. The muscle magnetic resonance imaging (MRI) pattern is highly variable among patients and families. Primary myoblast culture from these patients demonstrated common findings consistent with reduced proliferation and differentiation, diminished satellite cell pool, accelerated senescence of muscle, and signs of autophagy activation.

This essay is in response to the need for schools to move from crisis to adaptation. The essay is informed by the question: how might school leaders use conversation to effectively engage adaptation? Adaptation is about transforming systems. We find that with adaptation as the aim, Transformative Leadership Conversation can be used to guide schools from crisis response to adaptation. The essay lays out suggestions in a theory of action for how school leaders can use conversation to move from crisis to adaptation. These suggestions include the use of framing, questioning, and listening.

Abstract Cerebral white matter lesions prevent cortico-spinal descending inputs from effectively activating spinal motoneurons, leading to loss of motor control. However, in most cases, the damage to cortico-spinal axons is incomplete offering a potential target for therapies aimed at improving volitional muscle activation. Here we hypothesize that, by engaging direct excitatory connections to cortico-spinal motoneurons, stimulation of the motor thalamus could facilitate activation of surviving cortico-spinal fibers thereby immediately potentiating motor output. To test this hypothesis, we identify optimal thalamic targets and stimulation parameters that enhance upper-limb motor-evoked potentials and grip forces in anesthetized monkeys. This potentiation persists after white matter lesions. We replicate these results in humans during intra-operative testing. We then design a stimulation protocol that immediately improves strength and force control in a patient with a chronic white matter lesion. Our results show that electrical stimulation targeting surviving neural pathways can improve motor control after white matter lesions.

Maternal vaccination is a safe and effective means of preventing infection in pregnant women, their fetuses, and infants after birth. Several vaccines are routinely administered in pregnancy as a valuable part of prenatal care with supporting recommendations from national and international health organizations. Fears concerning vaccine safety in pregnancy are pervasive despite sufficient available safety data to support their use, leading to underutilization of maternal immunization. Despite this hesitancy, the field of maternal vaccination is evolving to include more vaccines in the routine prenatal vaccination schedule, including the new RSV vaccine. This review discusses the currently recommended vaccines in pregnancy, evidence for their use, and an overview of ongoing clinical trials investigating prospective vaccines for pregnant women.

Background: Important tools in preventing the spread of COVID-19 include contract tracing and adherence to isolation guidelines after a positive diagnosis of COVID-19. This is especially relevant among college students who are often away from support systems at home, living in high-density housing, and may not experience serious symptoms from COVID-19 while still contagious. Objective: As text message-based interventions have been found effective in addressing health behaviors among young adults, we conducted formative research to explore how text messaging could support students in adhering to isolation guidelines. Participants: A convenience sample of college students (n = 104) at one university. Methods: An online survey gathered students' perceptions of helpful components to include in a text message-based intervention. Results: Students expressed interest in receiving text messages with support, encouragement, and resources during their time in isolation following a COVID-19 diagnosis. Conclusions: Based on the results, we developed a text message-based intervention designed to provide motivation, support, distraction, and information on resources.

Summary Fungal infections, a leading cause of mortality among eukaryotic pathogens, pose a growing global health threat due to the rise of drug-resistant strains. New therapeutic strategies are urgently needed to combat this challenge. The PCA pathway for biosynthesis of Co-enzyme A (CoA) and Acetyl-CoA (AcCoA) from vitamin B5 (pantothenic acid) has been validated as an excellent target for the development of new antimicrobials against fungi and protozoa. The pathway regulates key cellular processes including metabolism of fatty acids, amino acids, sterols, and heme. In this study, we provide genetic evidence that disruption of the PCA pathway in Saccharomyces cerevisiae results in a significant alteration in the susceptibility of fungi to a wide range of xenobiotics, including clinically approved antifungal drugs through alteration of vacuolar morphology and drug detoxification. The drug potentiation mediated by genetic regulation of genes in the PCA pathway could be recapitulated using the pantazine analog PZ-2891 as well as the celecoxib derivative, AR-12 through inhibition of fungal AcCoA synthase activity. Collectively, the data validate the PCA pathway as a suitable target for enhancing the efficacy and safety of current antifungal therapies.

Abstract Background The purpose of this report is to provide insight and details regarding the development and implementation of an injury and illness surveillance (IIS) system for the United States Olympic and Paralympic Committee (USOPC). Methods The development and deployment of the IIS employed a multiphase approach. First, researchers determined variables to include in the IIS using the recommendations from the 2020 IOC consensus statement for reporting sport epidemiological data. Second, the hosting and deployment platforms were comprehensively evaluated for their suitability, ease of use, flexibility, and backend data structure (for both capture and aggregation). Third, focus groups consisting of the Sports Medicine department leadership and clinicians piloted the IIS system and revisions were made based on their feedback. Pilot testing of the IIS and follow-up focus groups were then conducted among all departmental clinicians to solicit additional feedback and drive further revisions. Finally, the IIS system was piloted among providers working during the 2023 Pan American and Parapan American Games to refine the system for future Games. After reviewing all potential software platform options (electronic medical record [EMR] system, athlete management systems, secure data collection platforms), Qualtrics (Qualtrics, Provo, UT, USA) was selected to host the IIS system. This choice was made due to the inability of the EMR and athlete-management systems to make frequent updates, modify existing questions, and provide the necessary form logic for the variety of scenarios in which the IIS system would be deployed. Feedback from the department’s leadership and clinicians resulted in a number of changes, most notably being the ability to enter multiple diagnoses for a single injury event. Additionally, clinician feedback resulted in the creation of additional diagnostic codes not currently present in the OSIICS v14.0 diagnostic coding system, adding “non-sport” as an additional variable for injury setting, and developing a system for reporting return-to-sport date for time-loss injuries. Discussion A multi-stage process of extensive planning, stakeholder feedback, and ongoing updates is required in order to successfully develop and implement an IIS system within a National Olympic and Paralynpic Committee. This process can be used to inform the development and implementation of IIS systems in other sporting organizations.

Abstract Zika virus (ZikV) infection during pregnancy can cause congenital Zika syndrome (CZS) and neurodevelopmental delay in infants, of which the pathogenesis remains poorly understood. We utilize an established female pigtail macaque maternal-to-fetal ZikV infection/exposure model to study fetal brain pathophysiology of CZS manifesting from ZikV exposure in utero. We find prenatal ZikV exposure leads to profound disruption of fetal myelin, with extensive downregulation in gene expression for key components of oligodendrocyte maturation and myelin production. Immunohistochemical analyses reveal marked decreases in myelin basic protein intensity and myelinated fiber density in ZikV-exposed animals. At the ultrastructural level, the myelin sheath in ZikV-exposed animals shows multi-focal decompaction, occurring concomitant with dysregulation of oligodendrocyte gene expression and maturation. These findings define fetal neuropathological profiles of ZikV-linked brain injury underlying CZS resulting from ZikV exposure in utero. Because myelin is critical for cortical development, ZikV-related perturbations in oligodendrocyte function may have long-term consequences on childhood neurodevelopment, even in the absence of overt microcephaly.

Abstract Sporadic venous malformations are genetic conditions primarily caused by somatic gain-of-function mutation of PIK3CA or TEK, an endothelial transmembrane receptor signaling through PIK3CA. Venous malformations are associated with pain, bleedings, thrombosis, pulmonary embolism, esthetic deformities and, in severe cases, life-threatening situations. No authorized medical treatment exists for patients with venous malformations. Here, we created a genetic mouse model of PIK3CA-related capillary venous malformations that replicates patient phenotypes. We showed that these malformations only partially signal through AKT proteins. We compared the efficacy of different drugs, including rapamycin, a mTORC1 inhibitor, miransertib, an AKT inhibitor and alpelisib, a PI3Kα inhibitor at improving the lesions seen in the mouse model. We demonstrated the effectiveness of alpelisib in preventing vascular malformations’ occurrence, improving the already established ones, and prolonging survival. Considering these findings, we were authorized to treat 25 patients with alpelisib, including 7 children displaying PIK3CA (n = 16) or TEK (n = 9)-related capillary venous malformations resistant to usual therapies including sirolimus, debulking surgical procedures or percutaneous sclerotherapies. We assessed the volume of vascular malformations using magnetic resonance imaging (MRI) for each patient. Alpelisib demonstrated improvement in all 25 patients. Vascular malformations previously considered intractable were reduced and clinical symptoms were attenuated. MRI showed a decrease of 33.4% and 27.8% in the median volume of PIK3CA and TEK malformations respectively, over 6 months on alpelisib. In conclusion, this study supports PI3Kα inhibition as a promising therapeutic strategy in patients with PIK3CA or TEK-related capillary venous malformations.

Abstract As the role of the Greenland Ice Sheet in the Arctic mercury (Hg) budget draws scrutiny, it is crucial to understand mercury cycling in glacial fjords, which control exchanges with the ocean. We present full water column measurements of total mercury (THg) and methylmercury (MeHg) in Sermilik Fjord, a large fjord in southeast Greenland fed by multiple marine-terminating glaciers, whose circulation and water mass transformations have been extensively studied. We show that THg (0.23-1.1 pM) and MeHg (0.02-0.17 pM) concentrations are similar to those in nearby coastal waters, while the exported glacially-modified waters are relatively depleted in inorganic mercury (Hg(II)), suggesting that inflowing ocean waters from the continental shelf are the dominant source of mercury species to the fjord. We propose that sediments initially suspended in glacier meltwaters scavenge particle-reactive Hg(II) and are subsequently buried, making the fjord a net sink of oceanic mercury.

Biological soil crusts (BSCs) play an essential role in soil stabilization and nutrient cycling in arid environments, being a hotspot of microbial activity including soil enzyme production. However, the changes in microbial communities of the BSCs from different age are poorly understood. In over a 60-year dune revegetation chronosequence (2021, 2016, 1973, and 1962) in the southeastern Tengger Desert, China, we compared the development of BSCs and underlying sands using metagenome sequencing and enzyme assays. In both BSCs and the underlying sand substrate, enzyme activity increased along the time series but was always greater for BSCs than the substrate, emphasizing the potential for nutrient cycling activity. A clear trend in community composition and co-occurrence network complexity was observed in the BSCs: the family-level taxonomic network of BSCs became more connected in the older age BSCs, while in the substrate, there was no such trend. Unexpectedly, considering their low relative abundance and diversity, archaea emerged as major keystones in establishing community networks, being key to network stability. In the underlying substrate, by contrast, archaea did not play this key role. During the time series of BSCs, the dominant archaeal groups were Nitrososphaeria, Methanomicrobia, Halobacteria, and an unclassified Thaumarchaeota, mainly linked to functional genes related to carbon and nitrogen, such as CHB2, xylA, amyA, amoB, nxrA, nxrB, and nirB. This suggests that in BSCs, the key role of archaea relates to their role in nitrogen cycling. This perspective adds to the emerging view that archaea play an important role in community structure and function in dryland environments.

**Introduction**: Plastic surgeons are maldistributed in New Zealand. Regional centres have fewer surgeons and lower surgeon to population ratios than larger metropolitan areas. There is no published data on the future work intentions of plastic surgical trainees in New Zealand. This study examines the career preferences and intentions of plastic surgery trainees in New Zealand as well as perceived barriers to working in a regional centre. **Methods**: An anonymous online survey was sent to 31 current plastic surgery trainees and recent graduates. Data collected included demographic information, rural background, previous experience in regional centres, family responsibilities, preferred work locations, aspirations for private practice and work–life balance preferences. **Results**: A total of 25 trainees completed the questionnaire, with a response rate of 81 per cent. A significant proportion of trainees have prior experience in smaller regional centres. Family-friendly work environments and employment for partners were identified as important considerations. The top-ranked regional centres to work in included Queenstown/Wānaka, Hawkes Bay, Nelson and Whangārei. Factors such as the presence of other plastic surgeons, leave policies, after-hours call arrangements and access to a private operating facility were considered essential. Financial considerations, access to quality schooling or childcare, employment opportunities for partners, opportunities for teaching and unit expansion were also important factors. **Conclusion**: The results of this survey provide insight into the personal and professional factors influencing the career decisions of plastic surgery trainees in New Zealand. The findings highlight the need for strategic workforce planning and engaging relevant stakeholders to address the maldistribution of plastic surgeons, ultimately improving access to specialised care and reducing healthcare disparities for New Zealanders.

Climatic extremes, especially extreme droughts, are occurring more frequently and profoundly impacting biogeochemical processes. However, the relative importance of microbial communities on soil nutrient cycling and community maintenance under natural extreme drought events remains elusive. During a record-breaking drought in the Yangtze River Basin (YRB) in the summer of 2022, we collected ambient soils and drought-affected bare and vegetated soils in ecological buffer zones from two sites with similar soil and vegetation characteristics along the YRB, and examined the relative contribution of soil bacterial communities in supporting multi-nutrient cycling index (MNCI) involving carbon-, nitrate- and phosphorus-cycling and their associations with microbial network. Extreme drought decreased (p < 0.05) bacterial α-diversity but increased MNCI in vegetated soils at both sites, while both remained unchanged (p > 0.05) in bare soils, possibly as a result of vegetation releasing rhizodeposits under drought which selectively recruited bacterial communities. Bacterial community compositions were shifted (p < 0.05) only in vegetated soils, and they exerted more influence than α-diversity on soil MNCI. Notably, the Anaerolineae, identified as a biomarker enriched in vegetated soils, had close associations with enzyme activities and soil MNCI at both sites, suggesting their potential recruitment by vegetation to withstand drought. Furthermore, key ecological clusters (Module 1) in bacterial co-occurrence networks at both sites supported (p < 0.05) higher MNCI, despite no substantial variation in network structure due to drought. Specifically, the most important taxa within Module 1 for predicting soil MNCI revealed by random forest modeling analysis (R2 = 0.44 - 0.63, p < 0.001), such as B1-7BS, SBR1031 and Nocardioides, could be deeply involved in soil nitrogen-cycling, suggesting an essential role of specialized interactions of bacterial communities in maintaining soil multifunctionality. Overall, this study demonstrates that changes in biomarkers and functional taxa under extreme drought may better reflect the biological mechanisms involved in microbial communities impacting ecosystem function, which may aid in forecasting the ecological consequences of ongoing climate change in the ecological buffer zones along the YRB.

Over the years, the field of forensic anthropology has become more diverse, bringing unique perspectives to a previously homogeneous field. This diversification has been accompanied by recognizing the need for advocacy and activism in an effort to support the communities we serve: marginalized communities that are often overrepresented in the forensic population. As such, forensic anthropologists see the downstream effects of colonialism, white supremacy, inequitable policies, racism, poverty, homophobia, transphobia, gun violence, and misogyny. Some argue that advocacy and activism have no place in forensic anthropological praxis. The counterarguments for engaging in advocacy and activism uphold white, heterosexual, cisgender, and ableist privilege by arguing that perceived objectivity and unbiased perspectives are more important than personally biasing experiences and positionality that supposedly jeopardize the science and expert testimony. Advocacy and activism, however, are not new to the practice of anthropology. Whether through sociocultural anthropology, archaeology, or other areas of biological anthropology, activism and advocacy play an important role, using both the scientific method and community engagement. Using a North American approach, we detail the scope of the issues, address how advocacy and activism are perceived in the wider discipline of anthropology, and define ways in which advocacy and activism can be utilized more broadly in the areas of casework, research, and education.

Abstract Web‐based studies of human dimensions are increasing across environmental and socio‐ecological disciplines. However, the prevalence of fraud threatens research quality. Increased fraud rates should be expected as surveys move progressively more online, motivated by expanding reach, cost savings and/or in response to COVID‐19. Web‐based research must better account for fraud to maintain confidence in findings. Practical diagnostic tools and data quality protocols are required to detect fraud and ensure results quality. Drawing on our experience using an online participatory mapping case study, we discuss methods to detect potentially fraudulent responses—and identify some limitations. We begin by reviewing the current state of knowledge on fraudulent responses or ‘fraudsters’ and its relative absence in environmental and socio‐ecological disciplines. We then describe our research approach, the indicators and variables we used to detect and assess fraud and our decision‐making process to eliminate suspicious responses without jeopardizing research integrity. We found that despite several preventative measures, many fraudulent respondents could provide survey responses and effectively mimicked legitimate respondents at first glance. By assuming each response to be ‘potentially fraudulent’, we determined that the complete screening of each respondent, while time‐consuming, can limit the prevalence of fraud. We also determined that the most common data consistency checks (e.g. duration, trap questions and straight‐liner checks) are unlikely to guarantee valid respondents. If not acknowledged and addressed, fraud has the potential to undermine data integrity, discredit research findings and limit the utility of results for policy. This study contributes to environmental and socio‐ecological research by reviewing existing fraudster literature and using our experience with fraud to provide recommendations for researchers to address this problem. We encourage researchers implementing online qualitative research methods to thoroughly assess and report fraud, when possible, to ensure widespread knowledge of this growing threat. Read the free Plain Language Summary for this article on the Journal blog.

Introduction: Sedimentary basins are naturally porous and permeable subsurface formations that underlie approximately half of the United States. In addition to being targets for geologic CO2 storage, these resources could supply geothermal power: sedimentary basin geothermal heat can be extracted with water or CO2 and used to generate electricity. The geothermal power potential of these basins and the accompanying implication for geologic CO2 storage are, however, understudied.Methods: Here, we use the Sequestration of CO2 Tool (SCO2TPRO) and the generalizable GEOthermal techno-economic simulator (genGEO) to address this gap by a) estimating the cost and capacity of sedimentary basin geothermal power plants across the United States and b) comparing those results to nationwide CO2 sequestration cost and storage potential estimates.Results and discussion: We find that across the United States, using CO2 as a geothermal heat extraction fluid reduces the cost of sedimentary basin power compared to using water, and some of the lowest cost capacity occurs in locations not typically considered for their geothermal resources (e.g., Louisiana, South Dakota). Additionally, using CO2 effectively doubles the sedimentary basin geothermal resource base, equating to hundreds of gigawatts of new capacity, by enabling electricity generation in geologies that are otherwise (with water) too impermeable, too thin, too cold, or not deep enough. We find there is competition for the best sedimentary basin resources between water- and CO2-based power, but no overlap between the lowest-cost resources for CO2 storage and CO2-based power. In this way, our results suggest that deploying CO2-based power may increase the cost of water based systems (by using the best resources) and the cost of CO2 storage (by storing CO2 in locations that otherwise may not be targeted). As such, our findings demonstrate that determining the best role for sedimentary basins within the energy transition may require balancing tradeoffs between competing priorities.

Introduction Black emerging adults (18–28 years) have the highest risk of short sleep duration and obesity. This increased risk may be partly explained by greater stress levels, which may result from race-related stress (racial discrimination and heightened race-related vigilance) or living in more disadvantaged home and neighbourhood environments. Insufficient sleep may also impact obesity risk via several weight-related mechanisms including energy balance, appetite and food reward, cortisol profiles and hydration status. This paper describes the rationale, design and methods for the Sleep, Health Outcomes and Body Weight (SHOW) study. This study aims to prospectively assess the effects of sleep, race-related stress and home/neighbourhood environments on weight-related mechanisms and obesity markers (body weight, waist circumference and fat mass) in 150 black emerging adults.Methods and analysis The SHOW study follows a measurement burst design that includes 3, 7-day data collection bursts (baseline, 6-month and 12-month follow-ups). Sleep is measured with three methods: sleep diary, actigraphy and polysomnography. Energy balance over 7 days is based on resting and postprandial energy expenditure measured via indirect calorimetry, physical activity via accelerometry and self-reported and ad libitum energy intake methods. Self-reported methods and blood biomarkers assess fasting and postprandial appetite profiles and a behavioural-choice task measures food reward. Cortisol awakening response and diurnal cortisol profiles over 3 days are assessed via saliva samples and chronic cortisol exposure via a hair sample. Hydration markers are assessed with 24-hour urine collection over 3 days and fasting blood biomarkers. Race-related stress is self-reported over 7 days. Home and neighbourhood environments (via the Windshield Survey) is observer assessed.Ethics and dissemination Ethics approval was granted by the University of North Carolina at Greensboro’s Institutional Review Board. Study findings will be disseminated through peer-reviewed publications, presentations at scientific meetings and reports, briefs/infographics for lay and community audiences.

Summary: The traditional view of hematopoiesis is that myeloid cells derive from a common myeloid progenitor (CMP), whereas all lymphoid cell populations, including B, T, and natural killer (NK) cells and possibly plasmacytoid dendritic cells (pDCs), arise from a common lymphoid progenitor (CLP). In Max41 transgenic mice, nearly all B cells seem to be diverted into the granulocyte lineage. Here, we show that these mice have an excess of myeloid progenitors, but their CLP compartment is ablated, and they have few pDCs. Nevertheless, T cell and NK cell development proceeds relatively normally. These hematopoietic abnormalities result from aberrant expression of Gata6 due to serendipitous insertion of the transgene enhancer (Eμ) in its proximity. Gata6 mis-expression in Max41 transgenic progenitors promoted the gene-regulatory networks that drive myelopoiesis through increasing expression of key transcription factors, including PU.1 and C/EBPa. Thus, mis-expression of a single key regulator like GATA6 can dramatically re-program multiple aspects of hematopoiesis.

Summary: Loss of muscle mass is a feature of chronic illness and aging. Here, we report that skeletal muscle-specific thrombospondin-1 transgenic mice (Thbs1 Tg) have profound muscle atrophy with age-dependent decreases in exercise capacity and premature lethality. Mechanistically, Thbs1 activates transforming growth factor β (TGFβ)-Smad2/3 signaling, which also induces activating transcription factor 4 (ATF4) expression that together modulates the autophagy-lysosomal pathway (ALP) and ubiquitin-proteasome system (UPS) to facilitate muscle atrophy. Indeed, myofiber-specific inhibition of TGFβ-receptor signaling represses the induction of ATF4, normalizes ALP and UPS, and partially restores muscle mass in Thbs1 Tg mice. Similarly, myofiber-specific deletion of Smad2 and Smad3 or the Atf4 gene antagonizes Thbs1-induced muscle atrophy. More importantly, Thbs1−/− mice show significantly reduced levels of denervation- and caloric restriction-mediated muscle atrophy, along with blunted TGFβ-Smad3-ATF4 signaling. Thus, Thbs1-mediated TGFβ-Smad3-ATF4 signaling in skeletal muscle regulates tissue rarefaction, suggesting a target for atrophy-based muscle diseases and sarcopenia with aging.

Abstract In brown adipose tissue (BAT), short-term cold exposure induces the activating transcription factor 4 (ATF4), and its downstream target fibroblast growth factor 21 (FGF21). Induction of ATF4 in BAT in response to mitochondrial stress is required for thermoregulation, partially by increasing FGF21 expression. In the present study, we tested the hypothesis that Atf4 and Fgf21 induction in BAT are both required for BAT thermogenesis under physiological stress by generating mice selectively lacking either Atf4 (ATF4 BKO) or Fgf21 (FGF21 BKO) in UCP1-expressing adipocytes. After 3 days of cold exposure, core body temperature was significantly reduced in ad-libitum-fed ATF4 BKO mice, which correlated with Fgf21 downregulation in brown and beige adipocytes, and impaired browning of white adipose tissue. Conversely, despite having reduced browning, FGF21 BKO mice had preserved core body temperature after cold exposure. Mechanistically, ATF4, but not FGF21, regulates amino acid import and metabolism in response to cold, likely contributing to BAT thermogenic capacity under ad libitum-fed conditions. Importantly, under fasting conditions, both ATF4 and FGF21 were required for thermogenesis in cold-exposed mice. Thus, ATF4 regulates BAT thermogenesis under fed conditions likely in a FGF21-independent manner, in part via increased amino acid uptake and metabolism.

Abstract The use of real-time magnetic resonance imaging (rt-MRI) of speech is increasing in clinical practice and speech science research. Analysis of such images often requires segmentation of articulators and the vocal tract, and the community is turning to deep-learning-based methods to perform this segmentation. While there are publicly available rt-MRI datasets of speech, these do not include ground-truth (GT) segmentations, a key requirement for the development of deep-learning-based segmentation methods. To begin to address this barrier, this work presents rt-MRI speech datasets of five healthy adult volunteers with corresponding GT segmentations and velopharyngeal closure patterns. The images were acquired using standard clinical MRI scanners, coils and sequences to facilitate acquisition of similar images in other centres. The datasets include manually created GT segmentations of six anatomical features including the tongue, soft palate and vocal tract. In addition, this work makes code and instructions to implement a current state-of-the-art deep-learning-based method to segment rt-MRI speech datasets publicly available, thus providing the community and others with a starting point for developing such methods.

ABSTRACTGovernment agencies have utilized Web Geographic Information Systems (GIS) dashboards to collect and disseminate spatial information on COVID-19. However, not all maps on these dashboards adhere to established cartographic principles. This article explores the extent of the cartographic issues by surveying state governments’ official COVID-19 websites in the United States on February 11, 2021. The results indicate that out of the fifty states, thirty-one (62.0%) incorrectly used unnormalized data in choropleth maps, sixteen (32.0%) used normalized data, and three (6.0%) did not employ choropleth maps. Among states using normalized data correctly, we identified other cartographic problems, including inappropriate data class divisions and suboptimal enumeration units. As dashboards serve as authoritative sources for health information, issues in map creation can influence public perception of the health crisis. These findings underscore the need for map standards to ensure the accuracy and reliability of health information in the Web GIS era.

Abstract A BiFeO3 film is grown epitaxially on a PrScO3 single crystal substrate which imparts ~ 1.45% of biaxial tensile strain to BiFeO3 resulting from lattice misfit. The biaxial tensile strain effect on BiFeO3 is investigated in terms of crystal structure, Poisson ratio, and ferroelectric domain structure. Lattice resolution scanning transmission electron microscopy, precession electron diffraction, and X-ray diffraction results clearly show that in-plane interplanar distance of BiFeO3 is the same as that of PrScO3 with no sign of misfit dislocations, indicating that the biaxial tensile strain caused by lattice mismatch between BiFeO3 and PrScO3 are stored as elastic energy within BiFeO3 film. Nano-beam electron diffraction patterns compared with structure factor calculation found that the BiFeO3 maintains rhombohedral symmetry, i.e., space group of R3c. The pattern analysis also revealed two crystallographically distinguishable domains. Their relations with ferroelectric domain structures in terms of size and spontaneous polarization orientations within the domains are further understood using four-dimensional scanning transmission electron microscopy technique.

Abstract Understanding the tumor microenvironment and genomic landscape is crucial for better prediction of treatment outcomes and developing novel therapies in Hodgkin lymphoma (HL). Recent advancements in genomics have enabled researchers to gain deeper insights into the genomic characteristics of HL at both single‐cell resolution and the whole genome level. The use of noninvasive methods such as liquid biopsies and formalin‐fixed paraffin‐embedded‐based imaging techniques has expanded the possibilities of applying cutting‐edge analyses to routine clinically available samples. Collaborative efforts between adult and pediatric group are imperative to translate novel findings into routine patient care.

Societal Impact Statement Plants are fundamental to terrestrial and aquatic ecosystems and are key to human livelihoods. To protect plant diversity, systematic approaches to conservation assessment are needed. Many nations have legislation or other policy instruments that seek to protect biodiversity (including plants), and species‐level assessments are essential for identifying the most threatened species that require special and immediate protection measures. Some plants occur in only one place (for instance, a single country) and here we have estimated how many of these ‘endemic’ species have had their threats assessed in each country or close country‐equivalent worldwide. We show that the level of assessment completion is only weakly related to the income of countries or the likely level of threat that species face. Summary The Global Strategy for Plant Conservation ambitiously called for an assessment of the conservation status of all recognised plant taxa by 2020. This target was not met in the short term. Nevertheless, the need for conservation assessments remains urgent as plants go extinct and face increasing threats from human impacts on the biosphere. Here, the completeness of threat assessments for endemic flora in 179 countries or their close equivalents was assessed. To do so, distribution information from the World Checklist of Vascular Plants was combined with assessments collated in the ThreatSearch database. The completeness of assessments was expected to be associated with the objective affluence of countries (measured using inequality‐adjusted Human Development Index (IHDI)) and/or the exposure of their plant species to threats associated with human impacts (measured using Global Human Modification index (GHM)). The number of endemic species per country was also hypothesised to influence the completion of assessments. Overall, 58% of all country‐based endemic species examined have no conservation assessment (127,643 species). Countries' progress toward the completion of threat assessments for endemic plants could not be confidently predicted by IHDI, GHM or the richness of endemic plant flora. The shortfall in threat assessments identified here restricts national regulation of actions which imperil plant species, with particular consequences for endemic plant species subject to local laws. Some nations with high IHDI scores (i.e. wealthier nations) are not systematically assessing extinction risk in their endemic species. Scarce funding should be directed to global hotspots of endemism with few available resources for assessment.

Objective To report epidemiological data regarding injury and illness among the Team USA staff during the Tokyo 2020 Summer Olympic and Paralympic Games and Beijing 2022 Winter Olympic and Paralympic Games.Methods A retrospective review of all Team USA staff (total staff, N=1703 (62.5% female); total staff days (SD)=34 489) medical encounters during the Tokyo 2020 Games and Beijing 2022 Games was conducted. Details related to injury and illness were evaluated. Incidence with 95% CI per 1000 staff days were calculated.Results A total of 32 illnesses (incidence [95% CI] 0.9 [0.6, 1.2]) and 23 injuries (incidence 0.7 [0.4, 0.9]) were sustained by the Team USA delegation staff members during the Tokyo 2020 Games and Beijing 2022 Games. Female staff reported more illnesses (illnesses proportion (IP) 2.9%; incidence 1.4 [0.8, 2.0]), while male staff incurred more injuries (IP 1.8%; incidence 0.9 [0.5, 1.3]). When stratified by physiological system, dermatological and infectious were the most common systems involved with illness (IP 0.5%; incidence 0.2 [0.1, 0.4]). Injuries to the upper limb were most common (IP 0.3%; incidence 0.3 [0.1, 0.5]).Conclusion Injury and illness rates among the Team USA staff during the Tokyo 2020 Games and Beijing 2022 Games were low, but notable. Knowledge of injury and illness risks contributes to staffing decisions and prevention strategies for staff supporting athletes during competition.

The heterodimeric kinesin-2 motor (KIF3A/KIF3B with accessory protein KAP3) drives intraflagellar transport, essential for ciliogenesis and ciliary function. Three point mutations in the KIF3B subunit have recently been linked to disease in humans (E250Q and L523P) and Bengal cats (A334T) (Cogné et al., Am. J. Hum. Genet., 2020, 106, 893–904). Patients display retinal atrophy and, in some cases, other ciliopathy phenotypes. However, the molecular mechanism leading to disease is currently unknown. Here, we used Kif3a−/−;Kif3b−/− (knockout) 3T3 cells, which cannot make cilia, to characterize these mutations. While reexpression of KIF3B(E250Q) and KIF3B(L523P) did not rescue ciliogenesis, reexpression of wildtype or KIF3B(A334T) restored ciliogenesis to wildtype levels. Fluorescent tagging revealed that the E250Q mutant decorated microtubules and thus is a rigor mutation. The L523P mutation, in the alpha-helical stalk domain, surprisingly did not affect formation of the KIF3A/KIF3B/KAP3 complex but instead impaired motility along microtubules. Lastly, expression of the A334T motor was reduced in comparison to all other motors, and this motor displayed an impaired ability to disperse the Golgi complex when artificially linked to this high-load cargo. In summary, this work uses cell-based assays to elucidate the molecular effects of disease-causing mutations in the KIF3B subunit on the kinesin-2 holoenzyme.

Summary: Primary cilia are essential signaling organelles that protrude from most cells in the body. Heterodimeric kinesin-2 (KIF3A/KIF3B/KAP3) powers several intracellular transport processes, including intraflagellar transport (IFT), essential for ciliogenesis. A long-standing question is how a motor protein is differentially regulated for specific cargos. Since phosphorylation of the KIF3A tail domain was suggested to regulate the activity of kinesin-2 for ciliogenesis, similarly as for the cytosolic cargo N-Cadherin, we set out to map the phosphosites involved in this regulation. Using well-characterized Kif3a−/−; Kif3b−/− mouse embryonic fibroblasts, we performed ciliogenesis rescue assays with a library of phosphomimetic mutants comprising all predicted phosphosites in the KIF3A tail domain. In contrast to previous reports, we found that KIF3A tail domain phosphorylation is dispensable for ciliogenesis in mammals. Thus, mammalian kinesin-2 is differently regulated for IFT than currently thought, consistent with the idea of differential regulation for ciliary and cytosolic cargo.

Summary: Clarifying the accumulation and decomposition of soil organic carbon (SOC) is crucial for comprehending carbon cycling in terrestrial ecosystems. SOC enrichment and decomposition lead to the fractionation of stable carbon isotopes, a complex process influenced by various factors, including microbes. However, this fractionation process during early soil formation and the role of microorganisms remain poorly explored. This study investigated the relative composition of stable carbon isotopes (δ13C) of recently formed biological soil crusts (BSCs) on stabilized sand dunes in the Tengger Desert, Northern China. A notable increase in δ13C was observed during early BSC development, likely driven by cyanobacteria’s direct fixation of CO2. Yet, δ13C values of BSCs gradually declined, approaching those of soils under native vegetation, probably linked to microbial succession within the BSCs. This finding highlights the potential microbial influence on early soil carbon turnover and underscores the effectiveness of isotope tracers for studying this process.

Background: As the state facing the second-largest nursing workforce shortage in the U.S. and low vaccination rates among residents early in the pandemic, Texas provided a unique opportunity to examine vaccine hesitancy and hesitant adoption among nursing students in an environment where state-level executive orders prohibited mandatory vaccinations. Methods: The purpose of this study was to describe the level of vaccine hesitancy and hesitant adoption among nursing students in the state of Texas. We used a convenient, opt-in, online survey of nursing students conducted between mid-April and mid-June 2022. The survey was distributed to all pre-licensure nursing programs in Texas. Results: The majority of survey respondents (n = 599) were between the ages of 18–28 (68 %), female (88 %) and white (57 %). Most received at least one dose of the COVID-19 vaccination (84 %). Of those receiving the vaccine, a high proportion (82 %) were identified as hesitant adopters. Respondents cited concerns about side effects (57 %) most frequently as the reason for vaccine hesitancy. Conclusion: Given the worldwide nursing shortage, factors potentially impacting the future workforce, such as vaccine hesitancy and hesitant adoption, must be closely monitored. More research is needed to understand the concerns of nursing students and the motivations of hesitant and non-hesitant adopters.

Introduction: Firearm sales and firearm-related injuries and deaths increased during the pandemic. Little is known about motivations for firearm purchasing in response to the COVID-19 pandemic and the mental health status of first-time purchasers. The purpose of this study was to estimate the association between firearm purchasing in response to the COVID-19 pandemic and anxiety symptoms, depressive symptoms, and stress. Methods: The authors analyzed data from a survey that approximated a nationally representative sample of American adults (N=3,528) who either did not own firearms (n=2,327) or purchased firearms for the first time in response to the pandemic (n=240). Self-reported stress, depressive symptoms, and anxiety symptoms were determined using standardized self-assessment questionnaires (Perceived Stress Scale, Patient Health Questionnaire, and Depression Anxiety Stress Scale, respectively). Using multivariable logistic regression, the association between firearm purchasing and each mental health measure were assessed after controlling for demographics and other determinants. Results: In each model, first-time firearm owners were more likely to be younger, live in urban areas, believe the government does too much for its citizens, stay home, stock up on items, and keep their children at home. First-time owners had significantly higher odds of anxiety and depressive symptoms than non-owners (AOR=1.05; 95% CI=1.04, 1.07 and AOR=1.15; 95% CI=1.04, 1.26, respectively). Conclusions: First-time firearm purchasers report higher depressive and anxiety symptoms than non-owners, suggesting that there may be a risk of suicide and other related firearm violence.

Natural resource managers need information about both human and natural systems and interactions between those systems. Much data is available, but mostly from disparate sources and data have often been collected at different time steps and at different geographic scales. We used insights from the literature to select 270 relevant variables, available at national scale, from 33 unique (Australian) data sources. There were numerous with repeat measures, so in total we have 425 variables: 143 specific to 2016, 148 specific to 2021, and 134 available for both periods. We used GIS to summarize the variables spatially based on two geographic boundaries: one describes 63 Natural Resource Management Regions; the other describes 419 (sub) bioregions (formally, IBRA – Interim Biogeographic Regionalisation for Australia). Data deficiencies prevented us from being able to report on all variables for all regions. In the NRM dataset many regions are offshore islands, about which data are not generally available. Moreover, many IBRA regions are small and household level data are not always available at that scale. For analyses requiring a complete dataset at a single time step, our 2021 dataset for NRM regions includes 270 unique variables that describe 56 regions. Our IBRA data includes 214 variables describing 409 regions. To help managers select appropriate data for specific problems/contexts, the metadata file also categorises variables according to (a) whether they pertain to the social or ecological system, or interactions; (b) the segment of society described (where relevant); and (c) the frequency with which data are updated.

Abstract Analysis of environmental DNA (eDNA) has gained widespread usage for taxonomically based biodiversity assessment. While interest in applying noninvasive eDNA monitoring for population genetic assessments has grown, its usage in this sphere remains limited. One barrier to uptake is that the effectiveness of eDNA detection below the species level remains to be determined for multiple species and environments. Here, we test the utility of this emergent technology to obtain within‐species haplotypic variation of New Zealand (NZ) blackfoot pāua (Haliotis iris). We compare mitochondrial haplotype diversity recovered from marine eDNA samples against traditional tissue samples of blackfoot pāua collected at the same NZ coastal site. Targeting the ATP8‐ATP6 region, we recovered four mitochondrial haplotypes from eDNA versus six haplotypes from tissue samples. Three common haplotypes were recovered with both eDNA and tissue samples, while only one out of three rare haplotypes – represented in tissue samples by one individual each – was recovered with our eDNA methods. We demonstrate that eDNA monitoring is an effective tool for recovering common genetic diversity from pāua, although rare (

Indigenous Peoples have been stewarding lands with fire for ecosystem improvement since time immemorial. These stewardship practices are part and parcel of the ways in which Indigenous Peoples have long recorded and protected knowledge through our cultural transmission practices, such as oral histories. In short, our Peoples have always been data gatherers, and as this article presents, we are also fire data gatherers and stewards. Given the growing interest in fire research with Indigenous communities, there is an opportunity for guidance on data collection conducted equitably and responsibly with Indigenous Peoples. This Special Issue of Fire presents fire research approaches and data harvesting practices with Indigenous communities as we “Reimagine the Future of Living and Working with Fire”. Specifically, the article provides future-thinking practices that can achieve equitable, sustainable, and just outcomes with and for stakeholders and rightholders (the preferred term Indigenous Peoples use in partnerships with academics, agencies, and NGOs). This research takes from the following key documents to propose an “Indigenous fire data sovereignty” (IFDS) framework: (1) Articles declared in the United Nations Declaration on the Rights of Indigenous Peoples (UNDRIP) as identified by the author and specified in Indigenous-led and allied Indigenous fire research in Australia, Canada, and the U.S.; (2) recommendations specific to cultural fire policy and calls for research in the 2023 Wildland Fire Mitigation and Management Commission report; (3) research and data barriers and opportunities produced in the 2024 Good Fire II report; and threads from (4) the Indigenous Fire Management conceptual model. This paper brings together recommendations on Indigenous data sovereignty, which are principles developed by Indigenous researchers for the protection, dissemination, and stewardship of data collected from Tribal/Nation/Aboriginal/First Nations Indigenous communities. The proposed IFDS framework also identifies potential challenges to Indigenous fire data sovereignty. By doing so, the framework serves as an apparatus to deploy fire research and data harvesting practices that are culturally informed, responsible, and ethically demonstrated. The article concludes with specific calls to action for academics and researchers, allies, fire managers, policymakers, and Indigenous Peoples to consider in exercising Indigenous fire data sovereignty and applying Indigenous data sovereignty principles to fire research.

Safe landings are imperative to accomplish NASA’s Artemis goal to enable human exploration on the Moon, including sample collection missions. However, a process known as plume surface interaction (PSI) presents a significant hazard to lunar landings. PSI occurs when the engine exhaust of a lander interacts with the surface ejecting large amounts of regolith particles at high velocities that can interfere with the landing, disturb the surface, and damage hardware. To better understand PSI, the particle impact event (PIE) sensor is being developed to measure the kinetic energy and the flux of ejecta during landings, to quantify the potential damage, and to quantify the ejecta displaced. Multiple parameters were estimated to define the PIE instrument requirements. These estimates demonstrate that ejecta can travel at velocities of up to 800 m/s and impact the surrounding area with energies of up to 400 µJ. A significant amount of ejecta can be deposited several 10 s of meters away from the landing site, modifying the surface and causing dust-related challenges. The PIE sensor will be launched for the first time in an upcoming lunar lander. Then, PIE measurements will be used to improve PSI prediction capabilities and develop mitigation strategies to ensure safe landings.

Triple-negative breast cancer (TNBC) is characterized by the absence of the estrogen receptor, progesterone receptor, and receptor tyrosine kinase HER2 expression. Due to the limited number of FDA-approved targeted therapies for TNBC, there is an ongoing need to understand the molecular underpinnings of TNBC for the development of novel combinatorial treatment strategies. This study evaluated the role of the MerTK receptor tyrosine kinase on proliferation and invasion/metastatic potential in TNBC. Immunohistochemical analysis demonstrated MerTK expression in 58% of patient-derived TNBC xenografts. The stable overexpression of MerTK in human TNBC cell lines induced an increase in proliferation rates, robust in vivo tumor growth, heightened migration/invasion potential, and enhanced lung metastases. NanoString nCounter analysis of MerTK-overexpressing SUM102 cells (SUM102-MerTK) revealed upregulation of several signaling pathways, which ultimately drive cell cycle progression, reduce apoptosis, and enhance cell survival. Proteomic profiling indicated increased endoglin (ENG) production in SUM102-MerTK clones, suggesting that MerTK creates a conducive environment for increased proliferative and metastatic activity via elevated ENG expression. To determine ENG’s role in increasing proliferation and/or metastatic potential, we knocked out ENG in a SUM102-MerTK clone with CRISPR technology. Although this ENG knockout clone exhibited similar in vivo growth to the parental SUM102-MerTK clone, lung metastasis numbers were significantly decreased ~4-fold, indicating that MerTK enhances invasion and metastasis through ENG. Our data suggest that MerTK regulates a unique proliferative signature in TNBC, promoting robust tumor growth and increased metastatic potential through ENG upregulation. Targeting MerTK and ENG simultaneously may provide a novel therapeutic approach for TNBC patients.

Forensic anthropology and, more broadly, the forensic sciences have only recently begun to acknowledge the importance of lived gender identity in the resolution of forensic cases, the epidemic of anti-transgender violence, and the need to seek practical solutions. The current literature suggests that forensic anthropologists are becoming aware of these issues and are working toward efforts to improve identification of transgender and gender diverse (TGD) persons. The scope of the problem, however, is not limited to methodology and instead can be traced to systemic anti-trans stigma ingrained within our cultural institutions. As such, we call on forensic anthropologists to counteract cisgenderism and transphobia and promote gender equity and inclusion in their practice. In this paper, we identify three areas in which forensic anthropologists may be positioned to intervene on cisgenderist practices and systems: in casework, research, and education. This paper aims to provide strategies for forensic anthropologists to improve resolution of TGD cases, produce more nuanced, gender-informed research, and promote gender equity and inclusion in the field.

Abstract Background In the ten years since the initial publication of the RenSeq protocol, the method has proved to be a powerful tool for studying disease resistance in plants and providing target genes for breeding programmes. Since the initial publication of the methodology, it has continued to be developed as new technologies have become available and the increased availability of computing power has made new bioinformatic approaches possible. Most recently, this has included the development of a k-mer based association genetics approach, the use of PacBio HiFi data, and graphical genotyping with diagnostic RenSeq. However, there is not yet a unified workflow available and researchers must instead configure approaches from various sources themselves. This makes reproducibility and version control a challenge and limits the ability to perform these analyses to those with bioinformatics expertise. Results Here we present HISS, consisting of three workflows which take a user from raw RenSeq reads to the identification of candidates for disease resistance genes. These workflows conduct the assembly of enriched HiFi reads from an accession with the resistance phenotype of interest. A panel of accessions both possessing and lacking the resistance are then used in an association genetics approach (AgRenSeq) to identify contigs positively associated with the resistance phenotype. Candidate genes are then identified on these contigs and assessed for their presence or absence in the panel with a graphical genotyping approach that uses dRenSeq. These workflows are implemented via Snakemake, a python-based workflow manager. Software dependencies are either shipped with the release or handled with conda. All code is freely available and is distributed under the GNU GPL-3.0 license. Conclusions HISS provides a user-friendly, portable, and easily customised approach for identifying novel disease resistance genes in plants. It is easily installed with all dependencies handled internally or shipped with the release and represents a significant improvement in the ease of use of these bioinformatics analyses.

Background: The autologous tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine is produced from dendritic cells (DC) loaded ex vivo with autologous tumor lysate (TL). TLPLDC has been shown to decrease recurrence in resected Stage III/IV melanoma patients in a Phase IIb trial. The TL particle only (TLPO) vaccine is produced by loading of yeast cell wall particles with autologous TL and direct injection allowing for in vivo DC loading. We have compared the TLPO and TLPLDC vaccines in an embedded Phase I/IIa trial of a larger Phase IIb trial of the TLPLDC vaccine. Methods: Patients rendered clinically disease-free after surgery were randomized 2:1 to receive the TLPO or TLPLDC vaccine and followed for recurrence and death. Patients had scheduled intradermal inoculations at 0, 1, 2, 6, 12, and 18 months after enrollment. Kaplan-Meier and log-rank analysis were used to compare disease-free survival (DFS) and overall survival (OS) in an intention-to-treat (ITT) analysis. Results: Sixty-three patients were randomized, 43 TLPO and 20 TLPLDC. Patients randomized to the TLPO arm were more likely to be female (37.2% vs. 10.0 %, p = 0.026), but otherwise no significant clinicopathological differences were identified. No differences in related adverse events (AE) were found between treatment arms. At a median follow-up of 20.5 months, the DFS (60.8% vs. 58.7 %, p = 0.714) and OS (94.6% vs. 93.8 %, p = 0.966) were equivalent between the TLPO and TLPLDC groups, respectively. No statistical differences were found in subgroup analyses between vaccine types, which accounted for receipt of immunotherapy and the use of G-CSF pre-blood draw. Conclusions: In a randomized, double-blind Phase I/IIa trial, there were no differences in DFS or OS in resected Stage III/IV melanoma patients receiving adjuvant TLPO versus TLPLDC vaccines. Given manufacturing advantages, further efficacy testing of TLPO is warranted in a Phase III trial.