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Chronic tendinopathy represents a growing healthcare burden in the ageing global population. Curative therapies remain elusive as the mechanisms that underlie chronic inflammation in tendon disease remain unclear. Identifying and isolating key pathogenic and reparative cells is essential in developing precision therapies and implantable materials for improved tendon healing. Multiple discrete human tendon cell populations have been previously described ex vivo. To determine if these populations persist in vitro, healthy human hamstring tenocytes were cultured for 8 d on either tissue culture plastic or aligned electrospun fibres of absorbable polydioxanone. Novel single-cell surface proteomics combined with unbiased single-cell transcriptomics (CITE-Seq) was used to identify discrete tenocyte populations. 6 cell populations were found, 4 of which shared key gene expression determinants with ex vivo human cell clusters: PTX3_PAPPA, POSTN_SCX, DCN_LUM and ITGA7_NES. Surface proteomics found that PTX3_PAPPA cells were CD10+CD26+CD54+. ITGA7_NES cells were CD146+ and POSTN_SCX cells were CD90+CD95+CD10+. Culture on the aligned electrospun fibres favoured 3 cell subtypes (DCN_LUM, POSTN_SCX and PTX3_ PAPPA), promoting high expression of tendon-matrix-associated genes and upregulating gene sets enriched for TNF-a and IL-6/STAT3 signalling. Discrete human tendon cell subpopulations persisted in in vitro culture and could be recognised by specific gene and surface-protein signatures. Aligned polydioxanone fibres promoted the survival of 3 clusters, including pro-inflammatory PTX3-expressing CD10+CD26+CD54+ cells found in chronic tendon disease. These results improved the understanding of preferred culture conditions for different tenocyte subpopulations and informed the development of in vitro models of tendon disease.

Objectives Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.Setting Prospective, international, multicentre, observational cohort study.Participants Patients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome 30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.Results This study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).Conclusions Patients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration number NCT04323644

Abstract Erythropoietin (EPO) plays a key role in energy metabolism, with EPO receptor (EpoR) expression in white adipose tissue (WAT) mediating its metabolic activity. Here, we show that male mice lacking EpoR in adipose tissue exhibit increased fat mass and susceptibility to diet-induced obesity. Our findings indicate that EpoR is present in WAT, brown adipose tissue, and skeletal muscle. Elevated EPO in male mice improves glucose tolerance and insulin sensitivity while reducing expression of lipogenic-associated genes in WAT, which is linked to an increase in transcription factor RUNX1 that directly inhibits lipogenic genes expression. EPO treatment in wild-type male mice decreases fat mass and lipogenic gene expression and increase in RUNX1 protein in adipose tissue which is not observed in adipose tissue EpoR ablation mice. EPO treatment decreases WAT ubiquitin ligase FBXW7 expression and increases RUNX1 stability, providing evidence that EPO regulates energy metabolism in male mice through the EPO-EpoR-RUNX1 axis.

Introduction: Patients with long bone fractures often present to the emergency department (ED) with severe pain and are typically treated with opioid and non-opioid analgesics. Historical data reveals racial disparities in analgesic administration, with White patients more likely to receive analgesics. With the diversifying US population, health equity is increasingly crucial. In this study we aimed to evaluate the early administration of opioid and non-opioid analgesia among Black and White patients with long bone and femur fractures in EDs over different time frames using a substantial database. Methods: We retrospectively extracted Information from 57 US healthcare organizations within the TriNetX database, encompassing 95 million patients. The ED records from 2003–2023 were subjected to propensity score matching for age and gender. We focused on four cohorts: two comprising Black and White patients diagnosed with long bone fractures, and another two with Black and White patients diagnosed solely with femur fractures. We examined analgesic administration rates over 20 years (2003–2023) at five-year intervals (2003–2008; 2008–2013; 2013–2018; 2018–2023), and further analyzed the rates for the most recent two-year period (2021–2023). Results: Disparities in analgesic administration significantly diminished over the study period. For patients with long bone fractures (1,095,052), the opioid administration gap narrowed from 6.3% to 1.1%, while non-opioid administration disparities reduced from 4.4% to 0.3%. Similar trends were noted for femur fractures (265,181). By 2021–2023, no significant differences in analgesic administration were observed between racial groups. Conclusion: Over the past 20 years, the gap in early administration of opioid and non-opioid analgesics for Black and White patients presenting with long bone fractures or femur fractures has been disappearing.

Abstract Background Describe trends in perpetrator characteristics and firearm use in pediatric homicides across the United States. Methods Multiply-imputed data from the Federal Bureau of Investigation’s 1976–2020 Supplementary Homicide Reports were used to estimate perpetrator characteristics (sex, age, and relationship to victim) and firearm use in pediatric homicides. Descriptive analyses were stratified by victim age group, sex, race, and five-year time periods. Results Family members were the most common perpetrator of infant and toddler (ages 0–4) and child (ages 5–12) homicides, whereas acquaintances accounted for the majority of adolescent (ages 13–19) homicides. Perpetrator characteristics vary across victim sex and race, particularly among adolescents. Despite overall stability, there were changes in perpetrator characteristics from 1976 to 2020. There was a sustained increase in the proportion of homicides committed with a firearm. In 2016–2020, the proportion of firearm-involved homicides was an all-time high for infant and toddler (14.8%), child (53.1%), and adolescent victims (88.5%). Conclusions Policy interventions that improve family stability and well-being may be most effective at preventing infant, toddler, and child homicides, whereas programs that target peer and community relationships, as well as policies that focus on firearm access, may be more crucial for preventing adolescent homicides.

Teacher shortages represent a global challenge for educator preparation programs (EPPs) and the districts they serve. Using mixed methods approach to data collection and analysis, this paper presents the findings of the three cases involving the use of student data and partner voices to highlight the benefits of intentionally integrating the concepts of Improvement Sciences, Equitable Experiences, educator preparation learning communities, and the changemaker mindset in the design of initiatives for addressing local teacher shortages. Results provide a ground-up perspective on promising strategies for local EPPs and school districts seeking to create a sustainable pipeline of quality educators by focusing on expanding access, success, and mobility for non-traditional student teachers (teacher candidates).

Social-justice teacher education literature is widespread, but research highlighting the perspectives and insights from those who lead is far less common. This interview-based case-study of 20 deans from the Schools of Education across the United States addresses this gap and explores insights that pertain to the leadership and implementation of teacher education programs that advance social justice and teacher agency. Using conceptualisations of thin and strong equity, we identify, explain, and discuss three themes which emerged from the data. The first involves addressing barriers and access issues for prospective teacher candidates. The second includes programmatic actions taken by deans in attempts to further social justice goals and the third highlights an understanding that social justice work inevitably includes working to change systems and structures at the societal scale. We explore the extent to which these patterns reflect strong equity and provide ideas for deepening this work through the development and reframing of teacher agency.

Abstract Elucidating genetic diversity within wild forms of modern crops is essential for understanding domestication and the possibilities of wild germplasm utilization. Gossypium hirsutum is a predominant source of natural plant fibers and the most widely cultivated cotton species. Wild forms of G. hirsutum are challenging to distinguish from feral derivatives, and truly wild populations are uncommon. Here we characterize a population from Mound Key Archaeological State Park, Florida using genome-wide SNPs extracted from 25 individuals over three sites. Our results reveal that this population is genetically dissimilar from other known wild, landrace, and domesticated cottons, and likely represents a pocket of previously unrecognized wild genetic diversity. The unexpected level of divergence between the Mound Key population and other wild cotton populations suggests that the species may harbor other remnant and genetically distinct populations that are geographically scattered in suitable habitats throughout the Caribbean. Our work thus has broader conservation genetic implications and suggests that further exploration of natural diversity in this species is warranted.

Locusts and other migratory grasshoppers are transboundary pests. Monitoring and control, therefore, involve a complex system made up of social, ecological, and technological factors. Researchers and those involved in active management are calling for more integration between these siloed but often interrelated sectors. In this paper, we bring together 38 coauthors from six continents and 34 unique organizations, representing much of the social-ecological-technological system (SETS) related to grasshopper and locust management and research around the globe, to introduce current topics of interest and review recent advancements. Together, the paper explores the relationships, strengths, and weaknesses of the organizations responsible for the management of major locust-affected regions. The authors cover topics spanning humanities, social science, and the history of locust biological research and offer insights and approaches for the future of collaborative sustainable locust management. These perspectives will help support sustainable locust management, which still faces immense challenges such as fluctuations in funding, focus, isolated agendas, trust, communication, transparency, pesticide use, and environmental and human health standards. Arizona State University launched the Global Locust Initiative (GLI) in 2018 as a response to some of these challenges. The GLI welcomes individuals with interests in locusts and grasshoppers, transboundary pests, integrated pest management, landscape-level processes, food security, and/or cross-sectoral initiatives.

Understanding vegetation recovery after fire is critical for predicting vegetation-mediated ecological dynamics in future climates. However, information characterizing vegetation recovery patterns after fire and their determinants over large geographical extents is limited. This study uses Moderate Resolution Imaging Spectroradiometer (MODIS) leaf area index (LAI) and albedo to characterize patterns of post-fire biophysical dynamics across the western United States (US) and further examines the influence of topo-climatic variables on the recovery of LAI and albedo at two different time horizons, 10 and 20 years post-fire, using a random forest model. Recovery patterns were derived for all wildfires that occurred between 1986 and 2017 across seven forest types and 21 level III ecoregions of the western US. We found differences in the characteristic trajectories of post-fire vegetation recovery across forest types and eco-climatic settings. In some forest types, LAI had recovered to only 60 %–70 % of the pre-fire levels by 25 years after the fire, while it recovered to 120 %–150 % of the pre-fire levels in other forest types, with higher absolute post-fire changes observed in forest types and ecoregions that had a higher initial pre-fire LAI. Our random forest results showed very little influence of fire severity on the recovery of both summer LAI and albedo at both post-fire time horizons. Post-fire vegetation recovery was most strongly controlled by elevation, with faster rates of recovery at lower elevations. Similarly, annual precipitation and average summer temperature had significant impacts on the post-fire recovery of vegetation. Full recovery was seldom observed when annual precipitation was less than 500 mm and average summer temperature was above the optimal range, i.e., 15–20 °C. Climate influences, particularly annual precipitation, were a major driver of post-fire summer albedo change through its impact on ecological succession. This study provides quantitative measures of primary controls that could be used to improve the modeling of ecosystem dynamics post-fire.

Background The mislabeling of seafood, wherein a food product’s marketed name does not match its contents, has the potential to mask species of conservation concern. Less discussed is the role of legally ambiguous market names, wherein a single name could be used to sell multiple species. Here we report the first study in Canada to examine mislabeling and ambiguous market names in both invertebrate (e.g., bivalve, cephalopod, shrimp) and finfish products. Methods A total of 109 invertebrate and 347 finfish products were sampled in Calgary between 2014 and 2020. Market names were documented from the label or equivalent and determined to be precise (the name could apply to only one species) or ambiguous (multiple species could be sold under that name). A region of the cytochrome c oxidase I gene was sequenced and compared to reference sequences from boldsystems.org. Samples were considered mislabeled if the species identified through DNA barcoding did not correspond to the market name, as determined through the Canadian Food Inspection Agency Fish List. Mislabeling was further differentiated between semantic mislabeling, wherein the market name was not found on the Fish List but the barcode identity was in line with what a consumer could reasonably have expected to have purchased; invalid market names, wherein the market name was so unusual that no legitimate inferences as to the product’s identity could be made; and product substitution, wherein the DNA barcode identified the product as a species distinct from that associated with the market name. Invalid market names and product substitutions were used to provide conservative estimates of mislabeling. The global conservation status of the DNA-identified invertebrate or finfish was determined through the International Union for the Conservation of Nature Red List. A logistic regression was used to determine the relationship between precision and accuracy in predicting conservation status of the sampled species. Results There was no significant difference in mislabeling occurrence between invertebrates (33.9% total mislabeling occurrence, 20.2% product substitution) and finfish (32.3% total mislabeling occurrence, 21.3% product substitution/invalid market names). Product substitutions sometimes involved species of conservation concern, such as foods marketed as freshwater eel (Anguilla rostrata) that were determined through DNA barcoding to be European eel (Anguilla anguilla), or cuttlefish balls putatively identified as the Endangered threadfin porgy (Evynnis cardinalis). Product substitutions and ambiguous market names were significantly associated with the sale of species of conservation concern, but ambiguity was a more important predictor. Although preventing the mislabeling of seafoods can and must remain a priority in Canada, our work suggests that moving towards precise names for all seafood products will better support sustainable fisheries goals.

Abstract Homeodomains (HDs) are the second largest class of DNA binding domains (DBDs) among eukaryotic sequence-specific transcription factors (TFs) and are the TF structural class with the largest number of disease-associated mutations in the Human Gene Mutation Database (HGMD). Despite numerous structural studies and large-scale analyses of HD DNA binding specificity, HD-DNA recognition is still not fully understood. Here, we analyze 92 human HD mutants, including disease-associated variants and variants of uncertain significance (VUS), for their effects on DNA binding activity. Many of the variants alter DNA binding affinity and/or specificity. Detailed biochemical analysis and structural modeling identifies 14 previously unknown specificity-determining positions, 5 of which do not contact DNA. The same missense substitution at analogous positions within different HDs often exhibits different effects on DNA binding activity. Variant effect prediction tools perform moderately well in distinguishing variants with altered DNA binding affinity, but poorly in identifying those with altered binding specificity. Our results highlight the need for biochemical assays of TF coding variants and prioritize dozens of variants for further investigations into their pathogenicity and the development of clinical diagnostics and precision therapies.

Abstract Laser Sintering (LS) is a type of Additive Manufacturing (AM) exploiting laser processing of polymeric particles to produce 3D objects. Because of its ease of processability and thermo-physical properties, polyamide-12 (PA-12) represents ~95% of the polymeric materials used in LS. This constrains the functionality of the items produced, including limited available colours. Moreover, PA-12 objects tend to biofoul in wet environments. Therefore, a key challenge is to develop an inexpensive route to introduce desirable functionality to PA-12. We report a facile, clean, and scalable approach to modification of PA-12, exploiting supercritical carbon dioxide (scCO2) and free radical polymerizations to yield functionalised PA-12 materials. These can be easily printed using commercial apparatus. We demonstrate the potential by creating coloured PA-12 materials and show that the same approach can be utilized to create anti-biofouling objects. Our approach to functionalise materials could open significant new applications for AM.

Abstract Metabolic and bariatric surgery (MBS) is widely considered the most effective option for treating obesity, a chronic, relapsing, and progressive disease. Recently, the American Society of Metabolic and Bariatric Surgery (ASMBS) and the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) issued new guidelines on the indications for MBS, which have superseded the previous 1991 National Institutes of Health guidelines. The aim of this study is to establish the first set of consensus guidelines for selecting procedures in Class I and II obesity, using an Expert Modified Delphi Method. In this study, 78 experienced bariatric surgeons from 32 countries participated in a two-round Modified Delphi consensus voting process. The threshold for consensus was set at an agreement or disagreement of ≥ 70.0% among the experts. The experts reached a consensus on 54 statements. The committee of experts reached a consensus that MBS is a cost-effective treatment option for Class II obesity and for patients with Class I obesity who have not achieved significant weight loss through non-surgical methods. MBS was also considered suitable for patients with Type 2 diabetes mellitus (T2DM) and a body mass index (BMI) of 30 kg/m2 or higher. The committee identified intra-gastric balloon (IGB) as a treatment option for patients with class I obesity and endoscopic sleeve gastroplasty (ESG) as an option for patients with class I and II obesity, as well as for patients with T2DM and a BMI of ≥ 30 kg/m2. Sleeve gastrectomy (1) and Roux-en-Y gastric bypass (RYGB) were also recognized as viable treatment options for these patient groups. The committee also agreed that one anastomosis gastric bypass (OAGB) is a suitable option for patients with Class II obesity and T2DM, regardless of the presence or severity of obesity-related medical problems. The recommendations for selecting procedures in Class I and II obesity, developed through an Expert Modified Delphi Consensus, suggest that the use of standard primary bariatric endoscopic (IGB, ESG) and surgical procedures (SG, RYGB, OAGB) are acceptable in these patient groups, as consensus was reached regarding these procedures. However, randomized controlled trials are still needed in Class I and II Obesity to identify the best treatment approach for these patients in the future.

Introduction: Folate, vitamin B9, is a water-soluble vitamin that is essential to cellular proliferation and division. In addition to the reduced folate carrier, eukaryotic cells take up folate through endocytosis mediated by one of two GPI-anchored folate receptors (FRs), FRα or FRβ. Two other isoforms of FR exist, FRγ and FRδ, neither of which support endocytic activities of FR signaling. FRβ is expressed primarily by monocytes and macrophages and highly expressed on activated macrophages. Macrophage expression of FRβ suggests a role for this receptor in modulating function of these immune sentinels, particularly as they engage in inflammatory processes. Despite several studies suggesting that folates can suppress inflammatory responses of macrophages to proinflammatory stimuli, there appears to be a lack of basic research examining the role of FRβ in modulating macrophage responses to microbial sensing. We therefore conducted a scoping review to assess evidence within the published literature addressing the question, “what is known about the extent to which FRβ regulates macrophage responses to sensing, and responding to, microorganisms?”. Methods: As a strategy for the study selection, we queried articles indexed in the research database PubMed and the search engine Google Scholar (up until August 12, 2023), including combinations of the research words: macrophage, folate receptor beta, FOLR2. Results: We identified 2 relevant articles out of 153 that are worth discussing here, none of which directly addressed our research question. Conclusion: There is an unmet need to better define the contribution of FRβ to regulating the macrophage response to microbes.

ABSTRACTThe aim of this study was to examine the acute effects of a non-caloric energy drink (C4E) compared to a traditional sugar-containing energy drink (MED) and non-caloric placebo (PLA) on exercise performance and cardiovascular safety. Thirty healthy, physically active males (25 ± 4 y) completed three experimental visits under semi-fasted conditions (5–10 h) and in randomized order, during which they consumed C4E, MED, or PLA matched for volume, appearance, taste, and mouthfeel. One hour after drink consumption, participants completed a maximal, graded exercise test (GXT) with measurement of pulmonary gases, an isometric leg extension fatigue test (ISOFTG), and had their cardiac electrical activity (ECG), leg blood flow (LBF), and blood pressure (BP) measured throughout the visit. Neither MED nor C4E had an ergogenic effect on maximal oxygen consumption, time to exhaustion, or peak power during the GXT (p > 0.05). Compared to PLA, MED reduced fat oxidation (respiratory exchange ratio (RER) +0.030 ± 0.01; p = 0.026) during the GXT and did not influence ISOFTG performance. Compared to PLA, C4E did not alter RER (p = 0.94) and improved impulse during the ISOFTG (+0.658 ± 0.25 V·s; p = 0.032). Relative to MED, C4E did not significantly improve gas exchange threshold (p = 0.05–0.07). Both MED and C4E increased systolic BP at rest (+7.1 ± 1.2 mmHg; p

Background“Kratom” refers to an array of bioactive products derived from Mitragyna speciosa, a tree indigenous to Southeast Asia. Most kratom consumers report analgesic and stimulatory effects, and common reasons for use are to address mental and physical health needs, manage pain, and to reduce use of other substances. Natural-history studies and survey studies suggest that many kratom consumers perceive benefits from those uses, but such studies are unlikely to capture the full range of kratom-use experiences.MethodsWe collected text data from Reddit posts from 2020-2022 to qualitatively examine conceptualizations, motivations, effects, and consequences associated with kratom use among people posting to social media. Reddit posts mentioning kratom were studied using template thematic analysis, which included collecting descriptions of kratom product types and use practices. Network analyses of coded themes was performed to examine independent relationships among themes, and between themes and product types.ResultsCodes were applied to 329 of the 370 posts that comprised the final sample; 134 posts contained kratom product descriptions. As Reddit accounts were functionally anonymous, demographic estimates were untenable. Themes included kratom physical dependence (tolerance, withdrawal, or use to avoid withdrawal), perceived addiction (net detrimental effects on functioning), and quitting. Extract products were positively associated with reports of perceived addiction, dependence, and experiences of quitting kratom. Many used kratom for energy and self-treatment of pain, fatigue, and problems associated with opioid and alcohol; they perceived these uses as effective. Consumers expressed frustrations about product inconsistencies and lack of product information.ConclusionAs in previous studies, kratom was deemed helpful for some and a hindrance to others, but we also found evidence of notable negative experiences with kratom products that have not been well documented in surveys. Daily kratom use may produce mild-moderate physical dependence, with greater severity being possibly more common with concentrated extracts; however, there are currently no human laboratory studies of concentrated kratom extracts. Such studies, and detailed kratom product information, are needed to help inform consumer decision-making.

IntroductionRupture of the gestational membranes often precedes major pregnancy complications, including preterm labor and preterm birth. One major cause of inflammation in the gestational membranes, chorioamnionitis (CAM) is often a result of bacterial infection. The commensal bacterium Streptococcus agalactiae, or Group B Streptococcus (GBS) is a leading infectious cause of CAM. Obesity is on the rise worldwide and roughly 1 in 4 pregnancy complications is related to obesity, and individuals with obesity are also more likely to be colonized by GBS. The gestational membranes are comprised of several distinct cell layers which are, from outermost to innermost: maternally-derived decidual stromal cells (DSCs), fetal cytotrophoblasts (CTBs), fetal mesenchymal cells, and fetal amnion epithelial cells (AECs). In addition, the gestational membranes have several immune cell populations; macrophages are the most common phagocyte. Here we characterize the effects of palmitate, the most common long-chain saturated fatty acid, on the inflammatory response of each layer of the gestational membranes when infected with GBS, using human cell lines and primary human tissue.ResultsPalmitate itself slightly but significantly augments GBS proliferation. Palmitate and GBS co-stimulation synergized to induce many inflammatory proteins and cytokines, particularly IL-1β and matrix metalloproteinase 9 from DSCs, CTBs, and macrophages, but not from AECs. Many of these findings are recapitulated when treating cells with palmitate and a TLR2 or TLR4 agonist, suggesting broad applicability of palmitate-pathogen synergy. Co-culture of macrophages with DSCs or CTBs, upon co-stimulation with GBS and palmitate, resulted in increased inflammatory responses, contrary to previous work in the absence of palmitate. In whole gestational membrane biopsies, the amnion layer appeared to dampen immune responses from the DSC and CTB layers (the choriodecidua) to GBS and palmitate co-stimulation. Addition of the monounsaturated fatty acid oleate, the most abundant monounsaturated fatty acid in circulation, dampened the proinflammatory effect of palmitate.DiscussionThese studies reveal a complex interplay between the immunological response of the distinct layers of the gestational membrane to GBS infection and that such responses can be altered by exposure to long-chain saturated fatty acids. These data provide insight into how metabolic syndromes such as obesity might contribute to an increased risk for GBS disease during pregnancy.

The snow cover extent across the Northern Hemisphere has diminished, while the number of lightning ignitions and amount of burned area have increased over the last 5 decades with accelerated warming. However, the effects of earlier snow disappearance on fire are largely unknown. Here, we assessed the influence of snow disappearance timing on fire ignitions across 16 ecoregions of boreal North America. We found spatially divergent trends in earlier (later) snow disappearance, which led to an increasing (decreasing) number of ignitions for the northwestern (southeastern) ecoregions between 1980 and 2019. Similar northwest–southeast divergent trends were observed in the changing length of the snow-free season and correspondingly the fire season length. We observed increases (decreases) over northwestern (southeastern) boreal North America which coincided with a continental dipole in air temperature changes between 2001 and 2019. Earlier snow disappearance induced earlier ignitions of between 0.22 and 1.43 d earlier per day of earlier snow disappearance in all ecoregions between 2001 and 2019. Early-season ignitions (defined by the 20 % earliest fire ignitions per year) developed into significantly larger fires in 8 out of 16 ecoregions, being on average 77 % larger across the whole domain. Using a piecewise structural equation model, we found that earlier snow disappearance is a good direct proxy for earlier ignitions but may also result in a cascade of effects from earlier desiccation of fuels and favorable weather conditions that lead to earlier ignitions. This indicates that snow disappearance timing is an important trigger of land–atmosphere dynamics. Future warming and consequent changes in snow disappearance timing may contribute to further increases in western boreal fires, while it remains unclear how the number and timing of fire ignitions in eastern boreal North America may change with climate change.

The parallel evolution of lateral plates and body shape in the threespine stickleback (Gasterosteus aculeatus) is an iconic example of adaptation. We test a case of contemporary evolutionary transition in a recently isolated population of marine G. aculeatus in British Columbia, Canada. We investigate Ectodysplasin (Eda) genotypes, plate counts, neutral genetic divergence, and whole-body phenotypes to determine the genetic and phenotypic distance between this population and nearby comparative populations. Our focal population is in the process of adapting both genetically and phenotypically to a freshwater environment, and we provide an example of the genetic basis for parallel evolution on a contemporary timescale. The frequency of Eda genotypes and lateral plate phenotypes in our focal population is not consistent with those of marine or fully freshwater populations. Although our focal population is genetically distinct from nearby marine populations, these fish still more closely resemble marine populations in overall body shape while demonstrating an intriguing intermediate phenotype. Eda frequency and lateral plate phenotype change faster than body shape in response to freshwater conditions, suggesting that the pace of adaptation differs across traits in response to the same environmental conditions. Our results further bolster the case for G. aculeatus as a key model of contemporary evolution.

Boreal and Arctic regions have warmed up to four times quicker than the rest of the planet since the 1970s. As a result, boreal and tundra ecosystems are experiencing more frequent and higher intensity extreme weather events and disturbances, such as wildfires. Yet limitations in ground and satellite data across the Arctic and boreal regions have challenged efforts to track these disturbances at regional scales. In order to effectively monitor the progression and extent of wildfires in the Arctic-boreal zone, it is essential to determine whether burned area (BA) products are accurate representations of BA. Here, we use 12 different datasets together with MODIS active fire data to determine the total yearly BA and seasonal patterns of fires in Arctic-boreal North America and Russia for the years 2001–2020. We found relatively little variability between the datasets in North America, both in terms of total BA and seasonality, with an average BA of 2.55 ± 1.24 (standard deviation) Mha/year for our analysis period, the majority (ca. 41%) of which occurs in July. In contrast, in Russia, there are large disparities between the products—GFED5 produces over four times more BA than GFED4s in southern Siberia. These disparities occur due to the different methodologies used; dNBR (differenced Normalized Burn Ratio) of short-term composites from Landsat images used alongside hotspot data was the most consistently successful in representing BA. We stress caution using GABAM in these regions, especially for the years 2001–2013, as Landsat-7 ETM+ scan lines are mistaken as burnt patches, increasing errors of commission. On the other hand, we highlight using regional products where possible, such as ABoVE-FED or ABBA in North America, and the Talucci et al. fire perimeter product in Russia, due to their detection of smaller fires which are often missed by global products.

Campylobacter jejuni is a common foodborne pathogen found in poultry that can cause severe life-threatening illnesses in humans. It is important to detect this pathogen in food to manage foodborne outbreaks. This study reports a novel impedimetric phage protein-based biosensor to detect C. jejuni NCTC 11168 at 100 CFU/mL concentrations using a genetically engineered receptor-binding phage protein, FlaGrab, as a bioreceptor. The electrochemical impedance spectroscopy (EIS) technique was employed to measure changes in resistance upon interaction with C. jejuni. The sensitivity of the phage protein-immobilized electrode was assessed using the various concentrations of C. jejuni NCTC 11168 ranging from 102–109 colony forming units (CFU)/mL). The change transfer resistance of the biosensor increased with increasing numbers of C. jejuni NCTC 11168 cells. The detection limit was determined to be approximately 103 CFU/mL in the buffer and 102 CFU/mL in the ex vivo samples. Salmonella enterica subsp. enterica serotype Typhimurium-291RH and Listeria monocytogenes Scott A were used as nontarget bacterial cells to assess the specificity of the developed biosensor. Results showed that the developed biosensor was highly specific toward the target C. jejuni NCTC 11168, as no signal was observed for the nontarget bacterial cells.

Background: Patient safety concerns have focused attention on organisational and safety cultures, in turn directing attention to the measurement of organisational and safety climates. Objectives: First, to compare levels of agreement between survey- and observation-based measures of organisational and safety climates/cultures and to compare both measures with criterion-based audits of the quality of care, using evidence-based markers drawn from national care standards relating to six common clinical conditions. (This required development of an observation-based instrument.) Second, to examine whether observation-based evaluations could replace or augment survey measurements to mitigate concerns about declining response rates and increasing social desirability bias. Third, to examine mediating factors in safety and organisational climate scores. Design: The study had three strands: (A) a postal questionnaire survey to elicit staff perceptions of organisational and safety climates, using six prevalidated scales; (B) semistructured non-participant observation of clinical teams; and (C) a retrospective criterion-based audit carried out by non-clinical auditors to minimise hindsight bias. Standardised summary scores were created for each strand, and pairs of measurements were compared (strand A with strand B, strand A with strand C, and strand B with strand C) using Bland–Altman plots to evaluate agreement. Correlations were also examined. Multilevel modelling of Strand A scores explored mediating factors. Setting and participants: Eight emergency departments and eight maternity units in England, UK. Interventions: None. Main outcome measures: Examination of feasibility, correlation and agreement. Results: Strand A: the overall response rate was 27.6%, whereas site-specific rates ranged from 9% to 47%. We identified more mediating factors than previous studies; variable response rates had little effect on the results. Organisational and safety climate scores were strongly correlated (r = 0.845) and exhibited good agreement [standard deviation (SD) differences 0.449; 14 (88%) within ± 0.5; one large difference]. Two commonly used scales had high levels of positive responses, suggesting positive climates or social desirability bias. Strand B: scoring on a four-point scale was feasible. Observational evaluation of teamwork culture was good but too limited for evaluating organisational culture. Strand C: a total of 359–399 cases were audited per condition. The results varied widely between different markers for the same condition, so selection matters. Each site performed well on some markers but not others, with few consistent patterns. Some national guidelines were contested. Comparisons: the comparison of safety climate (survey) and teamwork culture (observation) revealed a moderately low correlation (r = 0.316) and good agreement [SD differences 1.082; 7 (44%) within ±0.5; one large difference]. The comparison of safety climate (survey) and performance (audit) revealed lower correlation (r = 0.150, i.e. relationship not linear) but reasonably good agreement [SD differences 0.992; 9 (56%) within ± 0.5; two large differences]. Comparisons between performance (audit) and both organisational climate (survey) and teamwork culture (observation) showed negligible correlations (

Introduction: Erythropoietin (EPO) acts primarily in regulating red blood cell production mediated by high EPO receptor (EPOR) expression in erythroid progenitor cells. EPO activity in non-erythroid tissue is evident in mice with EPOR restricted to erythroid tissues (ΔEPORE) that become obese, glucose-intolerant, and insulin-resistant. In animal models, nitric oxide synthase (NOS) contributes to EPO activities including erythropoiesis, neuroprotection, and cardioprotection against ischemia-reperfusion injury. However, we found that extended EPO treatment to increase hematocrit compromised heart function, while the loss of neuronal NOS (nNOS) was protective against the deleterious activity of EPO to promote heart failure.Methods: Wild-type (WT) mice, ΔEPORE mice, and nNOS-knockout mice (nNOS−/−) were placed on a high-fat diet to match the ΔEPORE obese phenotype and were treated with EPO for 3 weeks. Hematocrit and metabolic response to EPO treatment were monitored. Cardiac function was assessed by echocardiography and ultrasonography.Results: ΔEPORE mice showed a decrease in the left ventricular outflow tract (LVOT) peak velocity, ejection fraction, and fractional shortening, showing that endogenous non-erythroid EPO response is protective for heart function. EPO treatment increased hematocrit in all mice and decreased fat mass in male WT, demonstrating that EPO regulation of fat mass requires non-erythroid EPOR. EPO treatment also compromised heart function in WT mice, and decreased the pulmonary artery peak velocity (PA peak velocity), LVOT peak velocity, ejection fraction, and fractional shortening, but it had minimal effect in further reducing the heart function in ΔEPORE mice, indicating that the adverse effect of EPO on heart function is not related to EPO-stimulated erythropoiesis. ΔEPORE mice had increased expression of heart failure-associated genes, hypertrophic cardiomyopathy-related genes, and sarcomeric genes that were also elevated with EPO treatment in WT mice. Male and female nNOS−/− mice were protected against diet-induced obesity. EPO treatment in nNOS−/− mice increased the hematocrit that tended to be lower than WT mice and decreased the PA peak velocity but did not affect the LVOT peak velocity, ejection fraction, and fractional shortening, suggesting that nNOS is required for the adverse effect of EPO treatment on heart function in WT mice. EPO treatment did not change expression of heart failure-associated gene expression in nNOS−/− mice.Discussion: Endogenous EPO has a protective effect on heart function. With EPO administration, in contrast to the protective effect to the cardiac injury of acute EPO treatment, extended EPO treatment to increase hematocrit in WT mice adversely affected the heart function with a corresponding increase in expression of heart failure-associated genes. This EPO activity was independent of EPO-stimulated erythropoiesis and required EPOR in non-erythroid tissue and nNOS activity, while nNOS−/− mice were protected from the EPO-associated adverse effect on heart function. These data provide evidence that nNOS contributes to the negative impact on the heart function of high-dose EPO treatment for anemia.

Retrogressive thaw slumps (RTS) are a form of abrupt permafrost thaw that can rapidly mobilize ancient frozen soil carbon, magnifying the permafrost carbon feedback. However, the magnitude of this effect is uncertain, largely due to limited information about the distribution and extent of RTS across the circumpolar region. Although deep learning methods such as Convolutional Neural Networks (CNN) have shown the ability to map RTS from high-resolution satellite imagery (≤10 m), challenges remain in deploying these models across large areas. Imagery selection and procurement remain one of the largest challenges to upscaling RTS mapping projects, as the user must balance cost with resolution and sensor quality. In this study, we compared the performance of three satellite imagery sources that differed in terms of sensor quality and cost in predicting RTS using a Unet3+ CNN model and identified RTS characteristics that impact detectability. Maxar WorldView imagery was the most expensive option, with a ground sample distance of 1.85 m in the multispectral bands (downloaded at 4 m resolution). Planet Labs PlanetScope imagery was a less expensive option with a ground sample distance of approximately 3.0–4.2 m (downloaded at 3 m resolution). Although PlanetScope imagery was downloaded at a higher resolution than WorldView, the radiometric footprint is around 10–12 m, resulting in less crisp imagery. Finally, Sentinel-2 imagery is freely available and has a 10 m resolution. We used 756 RTS polygons from seven sites across Arctic Canada and Siberia in model training and 63 RTS polygons in model testing. The mean IoU of the validation and testing data sets were 0.69 and 0.75 for the WorldView model, 0.70 and 0.71 for the PlanetScope model, and 0.66 and 0.68 for the Sentinel-2 model, respectively. The IoU of the RTS class was nonlinearly related to the RTS Area, showing a strong positive correlation that attenuated as the RTS Area increased. The models were better able to predict RTS that appeared bright on a dark background and were less able to predict RTS that had higher plant cover, indicating that bare ground was a primary way the models detected RTS. Additionally, the models performed less well in wet areas or areas with patchy ground cover. These results indicate that all imagery sources tested here were able to predict larger RTS, but higher-quality imagery allows more accurate detection of smaller RTS.

The advent of induced pluripotent stem cell (iPSC) technology has brought about transformative advancements in regenerative medicine, offering novel avenues for disease modeling, drug testing, and cell-based therapies. Patient-specific iPSC-based treatments hold the promise of mitigating immune rejection risks. However, the intricacies and costs of producing autologous therapies present commercial challenges. The hair follicle is a multi-germ layered versatile cell source that can be harvested at any age. It is a rich source of keratinocytes, fibroblasts, multipotent stromal cells, and the newly defined Hair Follicle-Associated Pluripotent Stem Cells (HAP). It can also be obtained non-invasively and transported via regular mail channels, making it the ideal starting material for an autologous biobank. In this study, cryopreserved hair follicle-derived iPSC lines (HF-iPS) were established through integration-free vectors, encompassing a diverse cohort. These genetically stable lines exhibited robust expression of pluripotency markers, and showcased tri-lineage differentiation potential. The HF-iPSCs effectively differentiated into double-positive cKIT+/CXCR4+ definitive endoderm cells and NKX6.1+/PDX1+ pancreatic progenitor cells, affirming their pluripotent attributes. We anticipate that the use of plucked hair follicles as an accessible, non-invasive cell source to obtain patient cells, in conjunction with the use of episomal vectors for reprogramming, will improve the future generation of clinically applicable pancreatic progenitor cells for the treatment of Type I Diabetes.

The nitrogen-stable isotopes of plants can be used to verify the source of fertilizers, but the fertilizer uptake patterns in tea (Camellia sinensis) plants are unclear. In this study, potted tea plants were treated with three types of organic fertilizers (OFs), urea, and a control. The tea leaves were sampled over seven months from the top, middle, and base of the plants and analyzed for the δ15N and nitrogen content, along with the corresponding soil samples. The top tea leaves treated with the rapeseed cake OF had the highest δ15N values (up to 6.6‰), followed by the chicken manure, the cow manure, the control, and the urea fertilizer (6.5‰, 4.1‰, 2.2‰, and 0.6‰, respectively). The soil treated with cow manure had the highest δ15N values (6.0‰), followed by the chicken manure, rapeseed cake, control, and urea fertilizer (4.8‰, 4.0‰, 2.5‰, and 1.9‰, respectively). The tea leaves fertilized with rapeseed cake showed only slight δ15N value changes in autumn but increased significantly in early spring and then decreased in late spring, consistent with the delivery of a slow-release fertilizer. Meanwhile, the δ15N values of the top, middle, and basal leaves from the tea plants treated with the rapeseed cake treatment were consistently higher in early spring and lower in autumn and late spring, respectively. The urea and control samples had lower tea leaf δ15N values than the rapeseed cake-treated tea and showed a generalized decrease in the tea leaf δ15N values over time. The results clarify the temporal nitrogen patterns and isotope compositions of tea leaves treated with different fertilizer types and ensure that the δ15N tea leaf values can be used to authenticate the organic fertilizer methods across different harvest periods and leaf locations. The present results based on a pot experiment require further exploration in open agricultural soils in terms of the various potential fertilizer effects on the different variations of nitrogen isotope ratios in tea plants.

How our brain generates diverse neuron types that assemble into precise neural circuits remains unclear. Using Drosophila lamina neuron types (L1-L5), we show that the primary homeodomain transcription factor (HDTF) brain-specific homeobox (Bsh) is initiated in progenitors and maintained in L4/L5 neurons to adulthood. Bsh activates secondary HDTFs Ap (L4) and Pdm3 (L5) and specifies L4/L5 neuronal fates while repressing the HDTF Zfh1 to prevent ectopic L1/L3 fates (control: L1-L5; Bsh-knockdown: L1-L3), thereby generating lamina neuronal diversity for normal visual sensitivity. Subsequently, in L4 neurons, Bsh and Ap function in a feed-forward loop to activate the synapse recognition molecule DIP-β, thereby bridging neuronal fate decision to synaptic connectivity. Expression of a Bsh:Dam, specifically in L4, reveals Bsh binding to the DIP-β locus and additional candidate L4 functional identity genes. We propose that HDTFs function hierarchically to coordinate neuronal molecular identity, circuit formation, and function. Hierarchical HDTFs may represent a conserved mechanism for linking neuronal diversity to circuit assembly and function.

This research assesses the potential for misidentification of sex in individuals of South Asian ancestry using the Walker (2008) morphological skull sex estimation standard [1]. Chromosomal sex was assessed using proteomic analysis targeting sex chromosome-specific amylogenic peptides. Results showed that the Walker method produced incorrect classification for 36.7 % of individuals. Overwhelmingly, those incorrectly assigned were chromosomally male. Misidentification was due to males within the group having lower trait scores (i.e., more gracile traits) than the standard would predict. There was also a high level of overlap in trait scores between male and females indicating reduced expression of sexual dimorphism. The use of established multivariate statistical techniques improved accuracy of sex estimation in some cases, but larger osteological data sets from South Asian individuals are required to develop population-specific standards. We suggest that peptide analysis may provide a useful tool for the forensic anthropologist when assessing sex in populations without population specific osteological standards.

Photoreceptor cells in the vertebrate retina have a highly compartmentalized morphology for efficient phototransduction and vision. Rhodopsin, the visual pigment in rod photoreceptors, is densely packaged into the rod outer segment sensory cilium and continuously renewed through essential synthesis and trafficking pathways housed in the rod inner segment. Despite the importance of this region for rod health and maintenance, the subcellular organization of rhodopsin and its trafficking regulators in the mammalian rod inner segment remain undefined. We used super-resolution fluorescence microscopy with optimized retinal immunolabeling techniques to perform a single molecule localization analysis of rhodopsin in the inner segments of mouse rods. We found that a significant fraction of rhodopsin molecules was localized at the plasma membrane, at the surface, in an even distribution along the entire length of the inner segment, where markers of transport vesicles also colocalized. Thus, our results collectively establish a model of rhodopsin trafficking through the inner segment plasma membrane as an essential subcellular pathway in mouse rod photoreceptors.

Efficient intratumoral infiltration of adoptively transferred cells is a significant barrier to effectively treating solid tumors with adoptive cellular transfer (ACT) therapies. Our recent forward genetic, whole-genome screen identified T cell-intrinsic gene candidates that may improve tumor infiltration of T cells. Here, results are combined with five independent genetic screens using rank aggregation to improve rigor. This resulted in a combined total of 1,523 candidate genes – including 1,464 genes not currently being evaluated as therapeutic targets - that may improve tumor infiltration of T cells. Gene set enrichment analysis of a published human dataset shows that these gene candidates are differentially expressed in tumor infiltrating compared to circulating T cells, supporting translational potential. Importantly, adoptive transfer of T cells overexpressing gain-of-function candidates (AAK1ΔN125, SPRR1B, and EHHADH) into tumor-bearing mice resulted in increased T cell infiltration into tumors. These novel gene candidates may be considered as potential therapeutic candidates that can aid adoptive cellular therapy in improving T cell infiltration into solid tumors.

In the original publication [...]