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Arterial occlusion pressure (AOP) is influenced by the characteristics of the cuff used to measure AOP. Doppler ultrasound was used to measure AOP of the brachial and superficial femoral arteries using straight and curved blood flow restriction cuffs in 21 males and 21 females. Vessel diameter and blood flow were evaluated as independent predictors of AOP. Overall, there were no significant differences in AOP when using the straight and curved cuffs in the brachial (129 mmHg vs. 128 mmHg) or superficial femoral artery (202 mmHg vs. 200 mmHg), respectively. Overall, AOP was greater (p < 0.05) in males than in females in the arm (135 mmHg, 123 mmHg) and leg (211 mmHg, 191 mmHg). Brachial (0.376 mm, 0.323 mm) and superficial femoral (0.547 mm, 0.486 mm) arteries were larger (p = 0.016) in males than in females, respectively. Systolic blood pressure (SBP) and arm circumference were predictive of brachial artery AOP, whereas SBP, diastolic blood pressure, thigh circumference, and vessel diameter were predictive of superficial femoral artery AOP. Straight and curved cuffs are efficacious in the measurement of AOP in the arm and leg. Differences in vessel size may contribute to sex differences in AOP but this requires further investigation. [ABSTRACT FROM AUTHOR]

Aims: Anthracycline chemotherapy (AC) for breast cancer can cause cancer therapy‐related cardiac dysfunction (CTRCD) with resultant heart failure, traditionally defined as a reduction in left ventricular (LV) ejection fraction on echocardiography. In recent years, global longitudinal systolic strain (GLS) has been used to identify subclinical cardiac dysfunction prior to development of overt CTRCD. Recent harmonized guidelines have incorporated GLS into definitions for CTRCD to identify cardiac dysfunction and inform decisions regarding cardioprotective strategies. Methods and results: We evaluated subclinical dysfunction in breast cancer patients treated with AC and determined the echocardiographic and patient factors associated with significant GLS changes. One hundred fourteen HER2 negative patients treated with AC were prospectively recruited and underwent serial echocardiograms (LVEF and LVGLS) at three time points (prior to AC, 3 months, and 1 year). CTRCD was defined as an asymptomatic reduction in LVEF of 10% or symptomatic drop of 5% to LVEF <53%. Subclinical LV dysfunction was defined as a reduction of ≥10% in GLS compared with baseline, recognizing that this cut off identified an 'at risk cohort' rather than patients with established CTRCD. No participant demonstrated CTRCD by reduction in LVEF. Forty‐three patients (38%) demonstrated a ≥10% relative reduction in GLS at 12 months; 20/43 (47%) had a reduced absolute GLS to <16%, and were older, had hypertension, increased LV mass, lower baseline e′ velocity and GLS. GLS ≥20.5% at baseline yielded a sensitivity of 79% and specificity of 87% for a normal GLS (i.e., ≥16%) at 1 year despite a ≥10% reduction from baseline. Conclusions: We present a stepwise evaluation for subclinical LV dysfunction using both a relative reduction in GLS combined with an absolute reduction in GLS. We believe our findings may re‐stratify patients with a high baseline GLS into a lower risk group despite transient relative GLS decrements ≥10%. [ABSTRACT FROM AUTHOR]

There is a critical need for advancements in disease management strategies for wildlife, but free‐living animals pose numerous challenges that can hinder progress. Most disease management attempts involve fixed interventions accompanied by post hoc outcome assessments focused on success or failure. Though these approaches have led to valuable management advances, there are limitations to both the rate of advancement and amount of information that can be gained. As such, strategies that support more rapid progress are required. Sarcoptic mange, caused by epidermal infection with Sarcoptes scabiei mites, is a globally emerging and re‐emerging panzootic that exemplifies this problem. The bare‐nosed wombat (Vombatus ursinus), a marsupial endemic to southeastern Australia, is impacted by sarcoptic mange throughout its geographic range and enhanced disease management capabilities are needed to improve upon existing in situ methods. We sought to advance in situ wildlife disease management for sarcoptic mange in free‐living bare‐nosed wombats, implementing an adaptive approach using fluralaner (Bravecto, MSD Animal Health) and a structured process of learning and method‐optimisation. By using surveillance of treated wombats to inform real‐time management changes, we have demonstrated the efficacy of topically administered fluralaner at 45 and 85 mg/kg against sarcoptic mange. Importantly, we observed variation in the effects of 45 mg/kg doses, but through our adaptive approach found that 85 mg/kg doses consistently reduced mange severity. Through modifying our surveillance program, we also identified individual‐level variation in wombat observability and used this to quantify the level of surveillance needed to assess long‐term management success. Our adaptive intervention represents the first report of sarcoptic mange management with fluralaner in free‐living wildlife and evaluation of its efficacy in situ. This study illustrates how adapting interventions in real time can advance wildlife disease management and may be applicable to accelerating in situ improvements for other host–pathogen systems. [ABSTRACT FROM AUTHOR]

Objective: This study aims to examine how variation in physicians' treatment decisions for newborn deliveries responds to changes in the hospital‐level norms for obstetric clinical decision‐making. Data Sources: All hospital‐based births in Florida from 2003 through 2017. Study Design: Difference‐in‐differences approach is adopted that leverages obstetric unit closures as the source of identifying variation to exogenously shift obstetricians to a new, nearby hospital with different propensities to approach newborn deliveries less intensively. Data Extraction: Births attributed to physicians continuously observed 2 years before the closure event and 2 years after the closure event (treatment group physicians) or for identical time periods around a randomly assigned placebo closure date (control group physicians). Principal Findings: All of the physicians meeting our inclusion criteria shifted their births to a new hospital less than 20 miles from the hospital shuttering its obstetric unit. The new hospitals approached newborn births more conservatively, and treatment group physicians sharply became less aggressive in their newborn birth clinical management (e.g., use of C‐section). The immediate 11‐percentage point (33%) increase in delivering newborns without any procedure behavior change is statistically significant (p value <0.01) and persistent after the closure event; however, the physicians' payer and patient mix are unchanged. Conclusions: Obstetric physician behavior change appears highly malleable and sensitive to the practice patterns of other physicians delivering newborns at the same hospital. Incentives and policies that encourage more appropriate clinical care norms hospital‐wide could sharply improve physician treatment decisions, with benefits for maternal and infant outcomes. [ABSTRACT FROM AUTHOR]

Background: Individuals with high risk for lung cancer may benefit from lung cancer screening, but there are associated risks as well as benefits. Shared decision‐making (SDM) tools with personalized information may provide key support for patients. Understanding patient perspectives on educational tools to facilitate SDM for lung cancer screening may support tool development. Aim: This study aimed to explore patient perspectives related to a SDM tool for lung cancer screening using a qualitative approach. Methods: We elicited patient perspectives by showing a provider‐facing SDM tool. Focus group interviews that ranged in duration from 1.5 to 2 h were conducted with 23 individuals with high risk for lung cancer. Data were interpreted inductively using thematic analysis to identify patients' thoughts on and desires for a patient‐facing SDM tool. Results: The findings highlight that patients would like to have educational information related to lung cancer screening. We identified several key themes to be considered in the future development of patient‐facing tools: barriers to acceptance, preference against screening and seeking empowerment. One further theme illustrated effects of patient–provider relationship as a limitation to meeting lung cancer screening information needs. Participants also noted several suggestions for the design of technology decision aids. Conclusion: These findings suggest that patients desire additional information on lung cancer screening in advance of clinical visits. However, there are several issues that must be considered in the design and development of technology to meet the information needs of patients for lung cancer screening decisions. Patient or Public Contribution: Patients, service users, caregivers or members of the public were not involved in the study design, conduct, analysis or interpretation of the data. However, clinical experts in health communication provided detailed feedback on the study protocol, including the focus group approach. The study findings contribute to a better understanding of patient expectations for lung cancer screening decisions and may inform future development of tools for SDM. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Limited observational windows lead to conflicting results in studies examining educational differences in Alzheimer's disease and related dementias (ADRD) risk, due to observational window bias relative to onset of accelerated cognitive decline. This study tested a novel model to address observational window bias and tested for the presence and sources of disparities in accelerated cognitive declines due to ADRD. METHODS: The sample examined 167,314 cognitive assessments from 32,441 Health and Retirement Study participants. We implemented a parametric non‐linear nested longitudinal regression and reported multivariable‐adjusted nodal incidence ratios (aNIR). RESULTS: University degrees were associated with lower incidence (aNIR = 0.253, 95% confidence interval [CI] = [0.221 to 0.289], p < 0.001), while black participants had a higher incidence (aNIR = 1.995, [1.858 to 2.141], p < 0.001) of accelerated cognitive decline, adjusting for demographic, sociobehavioral, and medical risk factors. Sex‐stratified analyses identified diminished educational returns for women and increased incidence among minoritized women. DISCUSSION: Addressing observational window bias reveals large social inequalities in the onset of accelerated cognitive declines indicative of ADRD. Highlights: This study identifies observational window bias as a source of conflicting results among previous studies of educational achievement in Alzheimer's disease and related dementias (ADRD) disparities.The study locates preclinical accelerated cognitive decline, which is indicative of ADRD while occurring 10+ years prior to symptom onset, as a site to study ADRD disparities that mitigates observational window bias.A novel method, nested non‐linear regression, is developed to test for differences in the onset of accelerated cognitive decline.Educational and racial/ethnic disparities are demonstrated in the onset of accelerated cognitive decline, as are their intersecting differences with sex/gender. [ABSTRACT FROM AUTHOR]

Summary: Background: Genetic factors contribute to the risk and severity of metabolic dysfunction‐associated steatotic liver disease (MASLD). However, the utility of genetic testing in risk stratification remains poorly characterised. Aims: To examine the influence of genetic risk on advanced fibrosis and cirrhosis in patients with type 2 diabetes mellitus (T2DM) and the utility of a polygenic risk score (PRS) in screening guidelines. Methods: We prospectively enrolled adults aged ≥50 years with T2DM recruited from clinics. PRS was the sum of risk alleles in PNPLA3, TM6SF2 and SERPINA1 minus the protective variant in HSD17B13. We performed magnetic resonance elastography and vibration‐controlled transient elastography to assess for advanced fibrosis and cirrhosis. Results: Of 382 included patients, the mean age and BMI were 64.8 (±8.4) years and 31.7 (±6.2) kg/m2 respectively. The prevalence of advanced fibrosis and cirrhosis were 12.3% and 5.2% respectively; higher PRS was associated with increased risk of cirrhosis (2.7% vs. 7.5%, p = 0.037). High PRS was associated with increased risk of advanced fibrosis among those with fibrosis‐4 index (FIB‐4) index <1.3 (9.6% vs. 2.3%, p = 0.036) but was not significantly different in other FIB‐4 categories. Incorporating PRS determination into the American Gastroenterological Association and American Association for the Study of Liver Diseases screening guidelines prevented approximately 20% of all participants with advanced fibrosis from being inappropriately classified as low risk. Conclusions: Utilising a well‐phenotyped, prospective cohort of adults with T2DM, we found that adding an assessment of genetic risk to recommendations to screen at‐risk populations may improve risk prediction. [ABSTRACT FROM AUTHOR]

Osteocrin (OSTN) is an endogenous protein sharing structural similarities with the natriuretic peptides [NPs; atrial (ANP), B‐type (BNP) and C‐type (CNP) NP], which are hormones known for their crucial role in maintaining pressure/volume homeostasis. Osteocrin competes with the NPs for binding to the receptor involved in their clearance (NPR‐C). In the present study, having identified, for the first time, the major circulating form of OSTN in human and ovine plasma, we examined the integrated haemodynamic, endocrine and renal effects of vehicle‐controlled incremental infusions of ovine proOSTN (83–133) and its metabolism in eight conscious normal sheep. Incremental i.v. doses of OSTN produced stepwise increases in circulating concentrations of the peptide, and its metabolic clearance rate was inversely proportional to the dose. Osteocrin increased plasma levels of ANP, BNP and CNP in a dose‐dependent manner, together with concentrations of their intracellular second messenger, cGMP. Increases in plasma cGMP were associated with progressive reductions in arterial pressure and central venous pressure. Plasma cAMP, renin and aldosterone were unchanged. Despite significant increases in urinary cGMP levels, OSTN administration was not associated with natriuresis or diuresis in normal sheep. These results support OSTN as an endogenous ligand for NPR‐C in regulating plasma concentrations of NPs and associated cGMP‐mediated bioactivity. Collectively, our findings support a role for OSTN in maintaining cardiovascular homeostasis. What is the central question of this study?What role does osteocrin (OSTN) have in integrated cardiovascular, renal and neurohumoral function in normal health?What is the main finding and its importance?Osteocrin is structurally similar to natriuretic peptides (NPs) that play a crucial role in cardiovascular homeostasis and binds to the NP receptor‐C (NPR‐C). Stepped doses of OSTN raised plasma atrial NP, B‐type NP, C‐type NP and cGMP and reduced arterial and venous pressures. Collectively, these findings provide strong evidence that increased NP levels result from competitive displacement from NPR‐C, not from increased NP secretion, suggesting that OSTN might play a role in maintaining cardiovascular homeostasis. [ABSTRACT FROM AUTHOR]

Summary: Leaf decomposition varies widely across temperate forests, shaped by factors like litter quality, climate, soil properties, and decomposers, but forest heterogeneity may mask local tree influences on decomposition and litter‐associated microbiomes. We used a 24‐yr‐old common garden forest to quantify local soil conditioning impacts on decomposition and litter microbiology.We introduced leaf litter bags from 10 tree species (5 arbuscular mycorrhizal; 5 ectomycorrhizal) to soil plots conditioned by all 10 species in a full‐factorial design. After 6 months, we assessed litter mass loss, C/N content, and bacterial and fungal composition. We hypothesized that (1) decomposition and litter‐associated microbiome composition would be primarily shaped by the mycorrhizal type of litter‐producing trees, but (2) modified significantly by underlying soil, based on mycorrhizal type of the conditioning trees.Decomposition and, to a lesser extent, litter‐associated microbiome composition, were primarily influenced by the mycorrhizal type of litter‐producing trees. Interestingly, however, underlying soils had a significant secondary influence, driven mainly by tree species, not mycorrhizal type. This secondary influence was strongest under trees from the Pinaceae.Temperate trees can locally influence underlying soil to alter decomposition and litter‐associated microbiology. Understanding the strength of this effect will help predict biogeochemical responses to forest compositional change. [ABSTRACT FROM AUTHOR]

Aims: Soluble fms‐like tyrosine kinase‐1 (sFlt‐1) and placental growth factor (PlGF), components of the vascular endothelial growth factor (VEGF) system, play key roles in angiogenesis. Reports of elevated plasma levels of sFlt‐1 and PlGF in coronary heart disease and heart failure (HF) led us to investigate their utility, and VEGF system gene single nucleotide polymorphisms (SNPs), as prognostic biomarkers in HF. Methods and results: ELISA assays for sFlt‐1, PlGF and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) were performed on baseline plasma samples from the PEOPLE cohort (n = 890), a study of outcomes among patients after an episode of acute decompensated HF. Eight SNPs potentially associated with sFlt‐1 or PlGF levels were genotyped. sFlt‐1 and PlGF were assayed in 201 subjects from the Canterbury Healthy Volunteers Study (CHVS) matched to PEOPLE participants. All‐cause death was the major endpoint for clinical outcome considered. In PEOPLE participants, mean plasma levels for both sFlt‐1 (125 ± 2.01 pg/ml) and PlGF (17.5 ± 0.21 pg/ml) were higher (both p < 0.044) than in the CHVS cohort (81.2 ± 1.31 pg/ml and 15.5 ± 0.32 pg/ml, respectively). sFlt‐1 was higher in HF with reduced ejection fraction compared to HF with preserved ejection fraction (p = 0.005). The PGF gene SNP rs2268616 was univariately associated with death (p = 0.016), and was also associated with PlGF levels, as was rs2268614 genotype. Cox proportional hazards modelling (n = 695, 246 deaths) showed plasma sFlt‐1, but not PlGF, predicted survival (hazard ratio 6.44, 95% confidence interval 2.57–16.1; p < 0.001) in PEOPLE, independent of age, NT‐proBNP, ischaemic aetiology, diabetic status and beta‐blocker therapy. Conclusions: Plasma sFlt‐1 concentrations have potential as an independent predictor of survival and may be complementary to established prognostic biomarkers in HF. [ABSTRACT FROM AUTHOR]

Premise Methods Results Conclusions Polypodium pellucidum, a fern endemic to the Hawaiian Islands, encompasses five ecologically and morphologically variable subspecies, suggesting a complex history involving both rapid divergence and rampant hybridization.We employed a large target‐capture data set to investigate the evolution of genetic, morphological, and ecological variation in P. pellucidum. With a broad sampling across five Hawaiian Islands, we deciphered the evolutionary history of P. pellucidum, identified nonhybrid lineages and intraspecific hybrids, and inferred the relative influence of geography and ecology on their distributions.Polypodium pellucidum is monophyletic, dispersing to the Hawaiian archipelago 11.53–7.77 Ma and diversifying into extant clades between 5.66 and 4.73 Ma. We identified four nonhybrid clades with unique morphologies, ecological niches, and distributions. Additionally, we elucidated several intraspecific hybrid combinations and evidence for undiscovered or extinct “ghost” lineages contributing to extant hybrid populations.We provide a foundation for revising the taxonomy of P. pellucidum to account for cryptic lineages and intraspecific hybrids. Geologic succession of the Hawaiian Islands through cycles of volcanism, vegetative succession, and erosion has determined the available habitats and distribution of ecologically specific, divergent clades within P. pellucidum. Intraspecific hybrids have likely arisen due to ecological and or geological transitions, often persisting after the local extinction of their progenitors. This research contributes to our understanding of the evolution of Hawai'i's diverse fern flora and illuminated cryptic taxa to allow better‐informed conservation efforts. [ABSTRACT FROM AUTHOR]

Two‐dimensional ultrasound (2DUS) echocardiography is the main noninvasive method used to evaluate cardiac function in animal models of myocardial infarction (MI). However, 2DUS echocardiography does not capture regional differences in cardiac contractility since it relies on planar images to estimate left ventricular (LV) geometry and global function. Thus, the current study was designed to evaluate the efficacy of a newly developed 4‐dimensional ultrasound (4DUS) method in detecting cardiac functional differences between two models of MI, permanent ligation (PL), and ischemia/reperfusion (I/R) in rats. We found that only 4DUS was able to detect LV global functional differences between the two models and that 4DUS‐derived surface area strain accurately detected infarcted regions within the myocardium that correlated well with histological infarct size analysis. We also found that 4DUS‐derived strain, which includes circumferential, longitudinal, and surface area strain, correlated with the peak positive of the first derivative of left ventricular pressure (+dP/dtmax). In conclusion, 4DUS strain echocardiography effectively assesses myocardial mechanics following experimentally induced ischemia in rats and accurately estimates infarct size as early as 1 day after injury. 4DUS also correlates well with +dP/dtmax, a widely used marker of cardiac contractility. [ABSTRACT FROM AUTHOR]

Background: Public contribution in research can lead to the design and conduct of more feasible and relevant research. However, our understanding of the acceptability and feasibility of public contribution and the evidence base regarding its impact in low‐ and middle‐income countries (LMICs) is limited. Methods: In this study protocol, we describe a mixed‐method examination of public contribution activities in the GuardiansCan project. The GuardiansCan project aims to respond to Tanzanian guardians' poor adherence to children's follow‐up care after treatment for acute lymphoblastic leukemia (ALL) with the help of Mobile Health technology. We aim to: (1) involve guardians of children treated for ALL as Guardians Advisory Board (GAB) members in the managing and undertaking, analysis and interpretation, and dissemination phases of the GuardiansCan project; and (2) examine the acceptability, feasibility, and perceived impact of GAB members' contribution to the GuardiansCan project from the perspective of the GAB members and public contribution coordinators. We will recruit six to eight guardians of children treated for ALL to the GAB. We will hold workshops where GAB members contribute to all project phases. Using impact logs, we will record GAB workshop activities and the perceived impact of these activities. We will interview GAB members and public contribution coordinators 6 months after establishing the GAB, and at the end of each study within the project, to examine the acceptability, feasibility, and perceived impact of public contribution activities. Discussion: We expect GAB contribution to increase project quality and relevance, and inform how to best embed public contribution in research in LMICs. [ABSTRACT FROM AUTHOR]

Aims: The influence of human factors on safety in healthcare settings is well established, with targeted interventions reducing risk and enhancing team performance. In experimental and early phase clinical research participant safety is paramount and safeguarded by guidelines, protocolized care and staff training; however, the real‐world interaction and implementation of these risk‐mitigating measures has never been subjected to formal system‐based assessment. Methods: Independent structured observations, systematic review of study documents, and interviews and focus groups were used to collate data on three key tasks undertaken in a clinical research facility (CRF) during a SARS CoV‐2 controlled human infection model (CHIM) study. The Systems Engineering Initiative for Patient Safety (SEIPS) was employed to analyse and categorize findings, and develop recommendations for safety interventions. Results: High levels of team functioning and a clear focus on participant safety were evident throughout the study. Despite this, latent risks in both study‐specific and CRF work systems were identified in all four SEIPS domains (people, environment, tasks and tools). Fourteen actionable recommendations were generated collaboratively. These included inter‐organization and inter‐study standardization, optimized checklists for safety critical tasks, and use of simulation for team training and exploration of work systems. Conclusions: This pioneering application of human factors techniques to analyse work systems during the conduct of research in a CRF revealed risks unidentified by routine review and appraisal, and despite international guideline adherence. SEIPS may aid categorization of system problems and the formulation of recommendations that reduce risk and mitigate potential harm applicable across a trials portfolio. [ABSTRACT FROM AUTHOR]

Populations may adapt to similar environments via parallel or non‐parallel genetic changes, but the frequency of these alternative mechanisms and underlying contributing factors are still poorly understood outside model systems. We used QTL mapping to investigate the genetic basis of highly divergent craniofacial traits between the scale‐eater (Cyprinodon desquamator) and molluscivore (C. brontotheroides) pupfish adapting to two different hypersaline lake environments on San Salvador Island, Bahamas. We lab‐reared F2 scale‐eater x molluscivore intercrosses from two different lake populations, estimated linkage maps, scanned for significant QTL for 29 skeletal and craniofacial traits, female mate preference, and sex. We compared the location of QTL between lakes to quantify parallel and non‐parallel genetic changes. We detected significant QTL for six craniofacial traits in at least one lake. However, nearly all shared QTL loci were associated with a different craniofacial trait within each lake. Therefore, our estimate of parallel evolution of craniofacial genetic architecture could range from one out of six identical trait QTL (low parallelism) to five out of six integrated trait QTL (high parallelism). We suggest that pleiotropy and trait integration can affect estimates of parallel evolution, particularly within rapid radiations. We also observed increased adaptive introgression in shared QTL regions, suggesting that gene flow contributed to parallel evolution. Overall, our results suggest that the same genomic regions may contribute to parallel adaptation across integrated suites of craniofacial traits, rather than specific traits, and highlight the need for a more expansive definition of parallel evolution. [ABSTRACT FROM AUTHOR]

The nucleoside analogue decitabine (or 5-aza-dC) is used to treat several haematological cancers. Upon its triphosphorylation and incorporation into DNA, 5-aza-dC induces covalent DNA methyltransferase 1 DNA–protein crosslinks (DNMT1-DPCs), leading to DNA hypomethylation. However, 5-aza-dC's clinical outcomes vary, and relapse is common. Using genome-scale CRISPR/Cas9 screens, we map factors determining 5-aza-dC sensitivity. Unexpectedly, we find that loss of the dCMP deaminase DCTD causes 5-aza-dC resistance, suggesting that 5-aza-dUMP generation is cytotoxic. Combining results from a subsequent genetic screen in DCTD-deficient cells with the identification of the DNMT1-DPC-proximal proteome, we uncover the ubiquitin and SUMO1 E3 ligase, TOPORS, as a new DPC repair factor. TOPORS is recruited to SUMOylated DNMT1-DPCs and promotes their degradation. Our study suggests that 5-aza-dC-induced DPCs cause cytotoxicity when DPC repair is compromised, while cytotoxicity in wild-type cells arises from perturbed nucleotide metabolism, potentially laying the foundations for future identification of predictive biomarkers for decitabine treatment. Synopsis: The chemotherapeutic decitabine/5-aza-dC induces covalent DNMT1 DNA-protein crosslinks (DPCs), leading to DNMT1 degradation and DNA hypomethylation. This study finds that E3 ligase TOPORS promotes DNMT1-DPC degradation, while deaminase DCTD mediates a DNMT1-independent mode of 5-aza-dC cytotoxicity. The dCMP deaminase DCTD mediates 5-aza-dC cytotoxicity independently of DNA-protein crosslink formation, through the generation of 5-aza-dUMP. The ubiquitin and SUMO1 E3 ligase TOPORS is a novel player in global-genome DPC repair. TOPORS is recruited to SUMOylated DNMT1-DPCs through its SUMO-interaction motifs, whereupon it promotes DNMT1-DPC ubiquitylation and degradation. TOPORS acts in parallel to the E3 ubiquitin ligase RNF4 in mediating DNMT1-DPC tolerance. TOPORS acts in parallel to the ubiquitin ligase RNF4 in degradation of DNMT1-DNA crosslinks, thereby mediating cellular tolerance to these DPCs. [ABSTRACT FROM AUTHOR]

In internal fertilisers, the precise timing of ovulation with the arrival of sperm at the site of fertilisation is essential for fertilisation success. In birds, mating is often not synchronised with ovulation, but instead females utilise specialised sperm storage tubules (SSTs) in the reproductive tract, which can ensure sperm are always available for fertilisation at the time of ovulation, whilst simultaneously providing a mechanism of post‐copulatory sexual selection. Despite the clear importance of SSTs for fertilisation success, we know little about the mechanisms involved in sperm acceptance, storage, and release. Furthermore, most research has been conducted on only a small number of species, based on which SSTs are usually assumed to look and function in the same way across all species. Here, we conduct a comparative exploration of SST morphology across 26 species of Galliformes. We show that SSTs, and the surrounding tissue, can vary significantly in morphology across species. We provide observational evidence that Galliformes exhibit at least 5 distinct categories of tubule types, including distinctive coiled and multi‐branched tubules, and describe 2 additional features of the surrounding tissue. We suggest functional explanations for variation in tubule morphology and propose next steps for future research. Our findings indicate that SSTs are likely to be far more variable than has previously been assumed, with potentially important consequences for our understanding of sperm storage in birds and post‐copulatory sexual selection in general. [ABSTRACT FROM AUTHOR]

Summary: Background: There are limited data on the prevalence and treatment of at‐risk metabolic dysfunction‐associated steatohepatitis (MASH) among patients with type 2 diabetes (T2DM) in the United States. Aim: To estimate the prevalence of at‐risk MASH in a prospectively recruited cohort of adults with T2DM using new nomenclature endorsed by multiple societies. Methods: This prospective study enrolled adults aged ≥50 with T2DM from primary care and endocrinology clinics in southern California from 2016 to 2023. Metabolic dysfunction‐associated steatotic liver disease (MASLD) was defined by an magnetic resonance imaging proton density fat fraction ≥5% and at least one metabolic risk factor without any other chronic liver disease or secondary cause for hepatic steatosis. Results: We included 530 adult patients with T2DM. The mean (±SD) age and body mass index (BMI) were 64.4 (±8.1) years and 31.5 (±6.1) kg/m2, respectively. Among patients with T2DM, the prevalence of MASLD, at‐risk MASH and cirrhosis was 69.6%, 13.6% and 6.8%, respectively. Among patients with co‐existing T2DM and obesity, the prevalence of MASLD, at‐risk MASH and cirrhosis was 77.8%, 15.9% and 9.0%, respectively, and was higher than in participants without obesity (p < 0.0001, 0.0543 and 0.0128, respectively). Conclusion: Among adults aged ≥50 years with T2DM, the prevalence of MASLD, at‐risk MASH and cirrhosis is high, posing a significant risk for liver‐related morbidity and mortality. Approximately 14% of patients with T2DM may be candidates for pharmacologic therapies specific to MASH‐related fibrosis. [ABSTRACT FROM AUTHOR]

Stewartia ovata (cav.) Weatherby, commonly known as mountain stewartia, is an understory tree native to the southeastern United States (U.S.). This relatively rare species occurs in isolated populations in Virginia, Kentucky, Tennessee, North Carolina, South Carolina, Georgia, Alabama, and Mississippi. As a species, S. ovata has largely been overlooked, and limited information is available regarding its ecology, which presents obstacles to conservation efforts. Stewartia ovata has vibrant, large white flowers that bloom in summer with a variety of filament colors, suggesting potential horticultural traits prized by ornamental industry. However, S. ovata is relatively slow growing and, due to long seed dormancy, propagation is challenging with limited success rates. This has created a need to assess the present genetic diversity in S. ovata populations to inform potential conservation and restoration of the species. Here, we employ a genotyping‐by‐sequencing (GBS) approach to characterize the spatial distribution and genetic diversity of S. ovata in the southern Appalachia region of the eastern United States. A total of 4475 single nucleotide polymorphisms (SNPs) were identified across 147 individuals from 11 collection sites. Our results indicate low genetic diversity (He = 0.216), the presence of population structure (K = 2), limited differentiation (FST = 0.039), and high gene flow (Nm = 6.16) between our subpopulations. Principal component analysis corroborated the findings of STRUCTURE, confirming the presence of two distinct S. ovata subpopulations. One subpopulation mainly contains genotypes from the Cumberland Plateau, Tennessee, while the other consists of genotypes present in the Great Smoky Mountain ranges in Tennessee, North Carolina, and portions of Nantahala, Chattahoochee‐Oconee national forests in Georgia, highlighting that elevation likely plays a major role in its distribution. Our results further suggested low inbreeding coefficient (FIS = 0.070), which is expected with an outcrossing tree species. This research further provides necessary insight into extant subpopulations and has generated valuable resources needed for conservation efforts of S. ovata. [ABSTRACT FROM AUTHOR]

Aim: Species responses to global warming will depend on intraspecific diversity, yet studies of factors governing biogeographic patterns of variability are scarce. Here, we investigate the evolutionary processes underlying genetic and phenotypic diversity in the flightless and cold‐adapted grasshopper Sigaus piliferus, and project its suitable space in time. Location: Te Ika‐a‐Māui Aotearoa—North Island of New Zealand. Methods: We used mitochondrial sequences to investigate population connectivity and demographic trends using phylogeographic tools and neutrality statistics. Metric data were used to document phenotypic variation using naïve clustering. We used niche metrics to assess intraspecific niche variation, and niche modelling to investigate suitability under past and future scenarios. Multiple matrix regressions with randomization explored the processes contributing to phenotypic differentiation among grasshopper populations. Results: Niche models and demographic analyses suggest suitable space for this grasshopper was more restricted during glacial than interglacial stages. Genealogical relationships among ND2 haplotypes revealed a deep north–south split partly concordant with phenotypic and niche variation, suggesting two ecotypes that have mixed during recolonisation of the central volcanic region. Multiple matrix regressions with randomization indicate a link between climate and phenotypic differentiation inferred from leg and pronotum dimensions but not pronotum shape. Niche projections predict severe habitat reduction due to climate warming. Main conclusions: The current distribution and intraspecific diversity of S. piliferus reflect complex biogeographical scenarios consistent with Quaternary climates and volcanism. Phenotypic divergence appears adaptive. Current levels of genetic and phenotypic variation suggest adaptive potential, yet the pace of anthropogenic warming over the next 50 years could result in small populations that may collapse before adapting. Differences in niche features between diverging intraspecific lineages suggest distinct responses to climate change, and this has implications for prioritising conservation actions and management strategies. [ABSTRACT FROM AUTHOR]

Objective: Understanding the spatial connectivity of elasmobranch populations is critical for regional fisheries management. The Blacktip Shark Carcharhinus limbatus is abundant in coastal waters of the Gulf of Mexico (GoM) and important in recreational and commercial fisheries. Based on genetic and tagging studies, GoM Blacktip Sharks are currently managed under separate quotas between the eastern and western GoM (divided at 88°W), but no studies have used vertebral chemistry to assess the population structure of adult Blacktip Sharks. Methods: We compared vertebral elemental signatures (barium [Ba], magnesium [Mg], manganese [Mn], strontium [Sr], and zinc [Zn]) for the first year of life with last occupied habitats (vertebral edges) in Blacktip Sharks collected from the western (Texas and Louisiana) and eastern (Alabama and Florida) coastal waters of the northern GoM. Result: We found significant regional differences in Ba, Mg, Mn, and Sr vertebral edge signatures, suggesting ecological separation of Blacktip Sharks. Significant correlation between first‐year and edge signatures suggested a high degree of residency between life stages. Cross‐validated discriminant function analyses yielded highest regional classification accuracies when Florida sharks were grouped separately west of 88°W (90%), demonstrating the unique elemental signatures of eastern versus western GoM Blacktip Sharks under current management delineations. Conclusion: Combined, these findings demonstrate that trace element markers can distinguish regional populations of Blacktip Sharks and provide a complimentary approach in addition to genetics and physical tagging to support current stock management efforts. Impact statementStocks of Blacktip Sharks are managed under separate quotas in the eastern and western Gulf of Mexico. In this study, elemental signatures in mineralized vertebral cartilage of Blacktip Sharks confirm ecological population separation. Natural chemical tags in shark vertebrae offer an additional tool to characterize population connectivity and stock delineation for highly migratory shark species. [ABSTRACT FROM AUTHOR]

Mantle convection plays a fundamental role in driving evolution of oceanic and continental lithosphere. In turn it impacts a broad suite of processes operating at or close to Earth's surface including landscape evolution, glacio‐eustasy, magmatism, and climate. A variety of theoretical approaches now exist to simulate mantle convection. Outputs from such simulations are being used to parameterize models of landscape evolution and basin formation. However, the substantial body of existing simulations has generated a variety of conflicting views on the history of dynamic topography, its evolution and key parameters for modeling mantle flow. The focus of this study is on developing strategies to use large‐scale quantitative stratigraphic observations to assess model predictions and identify simulation parameters that generate realistic predictions of Earth surface evolution. Spot measurements of uplift or subsidence provide useful target observations for models of dynamic topography, but finding areas where tectonics have not also influenced vertical motions is challenging. To address this issue, we use large inventories of stratigraphic data from across North America with contextual geophysical and geodetic data to constrain the regional uplift and subsidence history. We demonstrate that a suite of typical geodynamic simulations struggle to match the amplitude, polarity and timing of observed vertical motions. Building on recent seismological advances, we then explore strategies for understanding patterns of continental uplift and subsidence that incorporate (and test) predicted evolution of the lithosphere, asthenosphere and deep mantle. Our results demonstrate the importance of contributions from the uppermost mantle in driving vertical motions of continental interiors. Key Points: Large‐scale digital inventories of stratigraphic observations used to test predictions from mantle convection simulationsUseful diagnostics include net uplift and subsidence, absolute elevations, paleo‐water depthsUpper mantle thermo‐mechanical evolution—crucial for assessing sub‐plate support—constrained using stratigraphy [ABSTRACT FROM AUTHOR]

Background: Tumor recurrence remains the main barrier to survival after surgery for pleural mesothelioma (PM). Soluble mesothelin‐related protein (SMRP) and cancer antigen 125 (CA‐125) are established blood‐based biomarkers for monitoring PM. We prospectively studied the utility of these biomarkers after pleurectomy decortication (PD). Methods: Patients who underwent PD and achieved complete macroscopic resection with available preoperative SMRP levels were included. Tumor marker levels were determined within 60 days of three timepoints: (1) preoperation, (2) post‐operation, and (3) recurrence. Results: Of 356 evaluable patients, 276 (78%) had recurrence by the end of follow‐up interval. Elevated preoperative SMRP levels were associated with epithelioid histology (p < 0.013), advanced TNM (p < 0.001) stage, and clinical stage (p < 0.001). Preoperative CA‐125 levels were not significantly associated with clinical covariates. Neither biomarker was associated with survival or disease‐free survival. With respect to nonpleural and nonlymphatic recurrences, mean SMRP levels were elevated in patients with pleural (p = 0.021) and lymph node (p = 0.042) recurrences. CA‐125 levels were significantly higher in patients with abdominal (p < 0.001) and lymph node (p = 0.004) recurrences. Among patients with all three timepoints available, we observed an average decrease in SMRP levels by 1.93 nmol/L (p < 0.001) postoperatively and again an average increase at recurrence by 0.79 nmol/L (p < 0.001). There were no significant changes in levels of CA‐125 across the study timepoints (p = 0.47). Conclusions: Longitudinal changes in SMRP levels corresponded with a radiographic presence of disease in a subset of patients. SMRP surveillance could aid in detection of local recurrences, whereas CA‐125 could be helpful in recognizing abdominal recurrences. [ABSTRACT FROM AUTHOR]

There is a rich literature highlighting that pathogens are generally better adapted to infect local than novel hosts, and a separate seemingly contradictory literature indicating that novel pathogens pose the greatest threat to biodiversity and public health. Here, using Batrachochytrium dendrobatidis, the fungus associated with worldwide amphibian declines, we test the hypothesis that there is enough variance in "novel" (quantified by geographic and phylogenetic distance) host‐pathogen outcomes to pose substantial risk of pathogen introductions despite local adaptation being common. Our continental‐scale common garden experiment and global‐scale meta‐analysis demonstrate that local amphibian‐fungal interactions result in higher pathogen prevalence, pathogen growth, and host mortality, but novel interactions led to variable consequences with especially virulent host‐pathogen combinations still occurring. Thus, while most pathogen introductions are benign, enough variance exists in novel host‐pathogen outcomes that moving organisms around the planet greatly increases the chance of pathogen introductions causing profound harm. [ABSTRACT FROM AUTHOR]

Objective: Delay in referral for epilepsy surgery of patients with drug‐resistant epilepsy (DRE) is associated with decreased quality of life, worse surgical outcomes, and increased risk of sudden unexplained death in epilepsy (SUDEP). Understanding the potential causes of delays in referral and treatment is crucial for optimizing the referral and treatment process. We evaluated the treatment intervals, demographics, and clinical characteristics of patients referred for surgical evaluation at our level 4 epilepsy center in the U.S. Intermountain West. Methods: We retrospectively reviewed the records of patients who underwent surgery for DRE between 2012 and 2022. Data collected included patient demographics, DRE diagnosis date, clinical characteristics, insurance status, distance from epilepsy center, date of surgical evaluation, surgical procedure, and intervals between different stages of evaluation. Results: Within our cohort of 185 patients with epilepsy (99 female, 53.5%), the mean ± standard deviation (SD) age at surgery was 38.4 ± 11.9 years. In this cohort, 95.7% of patients had received definitive epilepsy surgery (most frequently neuromodulation procedures) and 4.3% had participated in phase 2 intracranial monitoring but had not yet received definitive surgery. The median (1st–3rd quartile) intervals observed were 10.1 (3.8–21.5) years from epilepsy diagnosis to DRE diagnosis, 16.7 (6.5–28.4) years from epilepsy diagnosis to surgery, and 1.4 (0.6–4.0) years from DRE diagnosis to surgery. We observed significantly shorter median times from epilepsy diagnosis to DRE diagnosis (p <.01) and epilepsy diagnosis to surgery (p <.05) in patients who traveled further for treatment. Patients with public health insurance had a significantly longer time from DRE diagnosis to surgery (p <.001). Significance: Both shorter distance traveled to our epilepsy center and public health insurance were predictive of delays in diagnosis and treatment intervals. Timely referral of patients with DRE to specialized epilepsy centers for surgery evaluation is crucial, and identifying key factors that may delay referral is paramount to optimizing surgical outcomes. [ABSTRACT FROM AUTHOR]

Demographic histories are frequently a product of the environment, as populations expand or contract in response to major environmental changes, often driven by changes in climate. Meso‐ and bathy‐pelagic fishes inhabit some of the most temporally and spatially stable habitats on the planet. The stability of the deep‐pelagic could make deep‐pelagic fishes resistant to the demographic instability commonly reported in fish species inhabiting other marine habitats, however the demographic histories of deep‐pelagic fishes are unknown. We reconstructed the historical demography of 11 species of deep‐pelagic fishes using mitochondrial and nuclear DNA sequence data. We uncovered widespread evidence of population expansions in our study species, a counterintuitive result based on the nature of deep‐pelagic ecosystems. Frequency‐based methods detected potential demographic changes in nine species of fishes, while extended Bayesian skyline plots identified population expansions in four species. These results suggest that despite the relatively stable nature of the deep‐pelagic environment, the fishes that reside here have likely been impacted by past changes in climate. Further investigation is necessary to better understand how deep‐pelagic fishes, by far Earth's most abundant vertebrates, will respond to future climatic changes. [ABSTRACT FROM AUTHOR]

Geothermal heat flow is a key parameter in governing ice dynamics, via its influence on basal melt and sliding, englacial rheology, and erosion. It is expected to exhibit significant lateral variability across Antarctica. Despite this, surface heat flow derived from Earth's interior remains one of the most poorly constrained parameters controlling ice sheet evolution. To obtain a continent‐wide map of Antarctic heat supply at regional‐scale resolution, we estimate upper mantle thermomechanical structure directly from VS. Until now, direct inferences of Antarctic heat supply have assumed constant crustal composition. Here, we explore a range of crustal conductivity and radiogenic heat production values by fitting thermodynamically self‐consistent geotherms to their seismically inferred counterparts. Independent estimates of crustal conductivity derived from VP are integrated to break an observed trade‐off between crustal parameters, allowing us to infer Antarctic geothermal heat flow and its associated uncertainty. Plain Language Summary: The future evolution of the Antarctic Ice Sheet depends on its stability, which describes how sensitive it is to environmental change. A key factor influencing ice sheet stability is how much thermal energy is transferred into its base from Earth's interior: a parameter called geothermal heat flow. If the level of heat supply is high, melting at the base of the ice sheet is encouraged, resulting in enhanced sliding toward outlet glaciers at the continental perimeter. Consequently, ice loss is accelerated, and the likelihood of glacial collapse is increased. Therefore, an accurate map of Antarctic geothermal heat flow, including how this parameter varies from region to region, is needed to produce high quality projections of Antarctic ice mass loss and therefore global sea level change. In this study, we use models of how seismic wave speed varies within Earth to estimate its three‐dimensional temperature structure, as well as its thermal conductivity. These data are used to infer a collection of best‐fitting models of Earth's thermal state, and hence estimate Antarctic geothermal heat flow. Key Points: Demonstration of new methodology for inferring geothermal heat flow from seismological dataS‐ and P‐wave velocity used together to infer and fit geothermsIncorporation of laterally varying crustal conductivity and heat production [ABSTRACT FROM AUTHOR]

A limited understanding of the pathology underlying chronic wounds has hindered the development of effective diagnostic markers and pharmaceutical interventions. This study aimed to elucidate the molecular composition of various common chronic ulcer types to facilitate drug discovery strategies. We conducted a comprehensive analysis of leg ulcers (LUs), encompassing venous and arterial ulcers, foot ulcers (FUs), pressure ulcers (PUs), and compared them with surgical wound healing complications (WHCs). To explore the pathophysiological mechanisms and identify similarities or differences within wounds, we dissected wounds into distinct subregions, including the wound bed, border, and peri‐wound areas, and compared them against intact skin. By correlating histopathology, RNA sequencing (RNA‐Seq), and immunohistochemistry (IHC), we identified unique genes, pathways, and cell type abundance patterns in each wound type and subregion. These correlations aim to aid clinicians in selecting targeted treatment options and informing the design of future preclinical and clinical studies in wound healing. Notably, specific genes, such as PITX1 and UPP1, exhibited exclusive upregulation in LUs and FUs, potentially offering significant benefits to specialists in limb preservation and clinical treatment decisions. In contrast, comparisons between different wound subregions, regardless of wound type, revealed distinct expression profiles. The pleiotropic chemokine‐like ligand GPR15L (C10orf99) and transmembrane serine proteases TMPRSS11A/D were significantly upregulated in wound border subregions. Interestingly, WHCs exhibited a nearly identical transcriptome to PUs, indicating clinical relevance. Histological examination revealed blood vessel occlusions with impaired angiogenesis in chronic wounds, alongside elevated expression of genes and immunoreactive markers related to blood vessel and lymphatic epithelial cells in wound bed subregions. Additionally, inflammatory and epithelial markers indicated heightened inflammatory responses in wound bed and border subregions and reduced wound bed epithelialization. In summary, chronic wounds from diverse anatomical sites share common aspects of wound pathophysiology but also exhibit distinct molecular differences. These unique molecular characteristics present promising opportunities for drug discovery and treatment, particularly for patients suffering from chronic wounds. The identified diagnostic markers hold the potential to enhance preclinical and clinical trials in the field of wound healing. [ABSTRACT FROM AUTHOR]

Aim: Pathophysiological differences between patients with heart failure with preserved (HFpEF) and reduced (HFrEF) ejection fraction (EF) remain unclear. Therefore we used a phenomics approach, integrating selected proteomics data with patient characteristics and cardiac structural and functional parameters, to get insight into differential pathophysiological mechanisms and identify potential treatment targets. Methods and results: We report data from a representative subcohort of the prospective Singapore Heart Failure Outcomes and Phenotypes (SHOP), including patients with HFrEF (EF <40%, n = 217), HFpEF (EF ≥50%, n = 213), and age‐ and sex‐matched controls without HF (n = 216). We measured 92 biomarkers using a proximity extension assay and assessed cardiac structure and function in all participants using echocardiography. We used multi‐block projection to latent structure analysis to integrate clinical, echocardiographic, and biomarker variables. Candidate biomarker targets were cross‐referenced with small‐molecule and drug databases. The total cohort had a median age of 65 years (interquartile range 60–71), and 50% were women. Protein profiles strongly discriminated patients with HFrEF (area under the curve [AUC] = 0.89) and HFpEF (AUC = 0.94) from controls. Phenomics analyses identified unique druggable inflammatory markers in HFpEF from the tumour necrosis factor receptor superfamily (TNFRSF), which were positively associated with hypertension, diabetes, and increased posterior and relative wall thickness. In HFrEF, interleukin (IL)‐8 and IL‐6 were possible targets related to lower EF and worsening renal function. Conclusion: We identified pathophysiological mechanisms related to increased cardiac wall thickness parameters and potentially druggable inflammatory markers from the TNFRSF in HFpEF. [ABSTRACT FROM AUTHOR]

The ongoing biodiversity and climate change crises require society to adopt nature‐based solutions that integrate and enhance ecosystems. To achieve successful implementation of nature‐based solutions, it is vital to communicate scientific information about their benefits and suitability.This article explores the potential of generative artificial intelligence (GenAI) as a tool for automating and scaling up science communication, outreach, and extension for nature‐based solutions.To illustrate the potential of GenAI, we present three case study examples; (1) reporting scientific information on ecosystem services, future land use options, and nature‐based solutions for farms (2) interactively providing guidance in response to homeowner questions about biodiversity‐friendly garden design and (3) visualising potential future scenarios of landscape change that incorporate diverse nature based and technological solutions. These examples demonstrate potential applications which may be relevant to other systems and types of nature‐based solutions.While GenAI for nature‐based solutions offers significant opportunities, this new technology brings risks of bias, false information, data privacy, mistrust, and high energy usage. Alongside technological development, we require integrated social research into ethics, public acceptability, and user experience, to maximise the benefits of GenAI while limiting these risks.GenAI offers an opportunity to accelerate the dissemination of nature‐based design strategies and reach a broader audience, by synthesising information and producing tailored content for specific users and locations. By harnessing the power of GenAI alongside human expertise, we can support nature‐based solutions to tackle the complex challenges of future sustainability. Read the free Plain Language Summary for this article on the Journal blog. Read the free Plain Language Summary for this article on the Journal blog. [ABSTRACT FROM AUTHOR]

INTRODUCTION: We aimed to investigate associations between common infections and neuroimaging markers of dementia risk (brain volume, hippocampal volume, white matter lesions) across three population‐based studies. METHODS: We tested associations between serology measures (pathogen serostatus, cumulative burden, continuous antibody responses) and outcomes using linear regression, including adjustments for total intracranial volume and scanner/clinic information (basic model), age, sex, ethnicity, education, socioeconomic position, alcohol, body mass index, and smoking (fully adjusted model). Interactions between serology measures and apolipoprotein E (APOE) genotype were tested. Findings were meta‐analyzed across cohorts (Nmain = 2632; NAPOE‐interaction = 1810). RESULTS: Seropositivity to John Cunningham virus associated with smaller brain volumes in basic models (β = −3.89 mL [−5.81, −1.97], Padjusted < 0.05); these were largely attenuated in fully adjusted models (β = −1.59 mL [−3.55, 0.36], P = 0.11). No other relationships were robust to multiple testing corrections and sensitivity analyses, but several suggestive associations were observed. DISCUSSION: We did not find clear evidence for relationships between common infections and markers of dementia risk. Some suggestive findings warrant testing for replication. [ABSTRACT FROM AUTHOR]

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Dollar stores have become the fastest‐growing retail format in the United States. However, there is considerable controversy regarding their entry, particularly into markets without grocery stores, and concerns that dollar‐store entry decisions are motivated by preemptive incentives. In this paper, we aim to study the market entry of dollar stores as an equilibrium phenomenon and to examine their impact on competing store formats in a dynamic environment. We use census‐tract level data and develop a dynamic model of oligopolistic competition to estimate the impact of dollar store entry on the equilibrium entry decisions of other retailers of the same format and other formats. We find that supermarkets and other large‐format owners thrive as dollar‐store expansion removes their "competitive fringe" in shared markets, whereas other small‐format stores (other dollar stores, convenience stores, and superettes) do not. Our findings have broad implications for the effect of dollar store entry on consumer welfare, as dollar‐store entry is not associated with grocery‐store exit but rather the exit of other small‐format stores. [ABSTRACT FROM AUTHOR]

Surface biofouling, corrosion, and wettability are important parameters to understand and characterize aluminum alloys to prevent the failure in marine environments. Antifouling technologies predominantly encompass chemical and biocidal approaches with negative environmental consequences. Therefore, this study focuses on a new method of producing non‐toxic and effective antifouling and corrosion‐resistant surfaces. In this study, ultrafast laser texturing is used to modify the surface of an aluminum alloy using a femtosecond laser system. Five different unique texture patterns are designed and fabricated using 3 W laser power, 100 kHz pulse repetition rate, and 4 mm s−1 scanning speed in order to make the aluminum surface antifouling and corrosion resistant. The non‐textured sample has a contact angle of 85° while the textured samples have contact angles of up to 157°. The contact angle increased with time up to 90 days of aging. Biofouling assessment is conducted using marine algae Nitzschia ovalis as a marine fouling test organism. A reduction of biofilm coverage of 79% is recorded from the laser‐produced star pattern texture. This study demonstrates that laser‐textured surfaces have the potential to mitigate the formation of biofilms on the surfaces while also providing a mechanism to control the relative level of corrosion. [ABSTRACT FROM AUTHOR]

Background: Citizen science is a way to democratise science by involving groups of citizens in the research process. Clinical guidelines are used to improve practice, but their implementation can be limited. Involving patients and the public can enhance guideline implementation, but there is uncertainty about the best approaches to achieve this. Citizen science is a potential way to involve patients and the public in improving clinical guideline implementation. We aimed to explore the application of citizen science methods to involve patients and the public in the dissemination and implementation of clinical guidelines in oral health and dentistry. Methods: We developed GUIDE (GUideline Implementation in oral health and DEntistry), a citizen science online platform, using a participatory approach with researchers, oral health professionals, guideline developers and citizens. Recruitment was conducted exclusively online. The platform focused on prespecified challenges related to oral health assessment guidelines, and asked citizens to generate ideas, as well as vote and comment on other citizens' ideas to improve those challenges. Citizens also shared their views via surveys and two online synchronous group meetings. Data were collected on participant's demographics, platform engagement and experience of taking part. The most promising idea category was identified by an advisory group based on engagement, feasibility and relevance. We presented quantitative data using descriptive statistics and analysed qualitative data using inductive and deductive thematic analysis. Results: The platform was open for 6 months and we recruited 189 citizens, from which over 90 citizens actively engaged with the platform. Most citizens were over 34 years (64%), female (58%) and had a university degree (50%). They generated 128 ideas, 146 comments and 248 votes. The challenge that led to most engagement was related to prevention and oral health self‐care. To take this challenge forward, citizens generated a further 36 ideas to improve a pre‐existing National Health Service oral care prevention leaflet. Citizens discussed motivations to take part in the platform (understanding, values, self‐care), reasons to stay engaged (communication and feedback, outputs and impact, and relevance of topics discussed) and suggestions to improve future platforms. Conclusion: Citizen science is an effective approach to generate and prioritise ideas from a group of citizens to improve oral health and dental services. Prevention and oral health self‐care were of particular interest to citizens. More research is needed to ensure recruitment of a diverse group of citizens and to improve retention in citizen science projects. Patient or Public Contribution: This project was inherently conducted with the input of public partners (citizen scientists) in all key aspects of its conduct and interpretation. In addition, two public partners were part of the research team and contributed to the design of the project, as well as key decisions related to its conduct, analysis, interpretation and dissemination and are co‐authors of this manuscript. [ABSTRACT FROM AUTHOR]

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Searches for phosphine in Venus' atmosphere have sparked a debate. Cordiner et al. (2022, https://doi.org/10.1029/2022gl101055) analyze spectra from the Stratospheric Observatory For Infrared Astronomy (SOFIA) and infer <0.8 ppb of PH3. We noticed that some spectral artifacts arose from non‐essential calibration‐load signals. By‐passing these signals allows simpler post‐processing and a 5.7σ candidate detection, suggesting ∼3 ppb of PH3 above the clouds. Compiling six phosphine results hints at an inverted abundance trend: decreasing above the clouds but rising again in the mesosphere from some unexplained source. However, no such extra source is needed if phosphine is undergoing destruction by sunlight (photolysis), to a similar degree as on Earth. Low phosphine values/limits are found where the viewed part of the super‐rotating Venusian atmosphere had passed through sunlight, while high values are from views moving into sunlight. We suggest Venusian phosphine is indeed present, and so merits further work on models of its origins. Plain Language Summary: Cordiner et al. (2022, https://doi.org/10.1029/2022gl101055) find no phosphine in Venus' atmosphere, using the airborne SOFIA telescope. By‐passing some instrumental effects, we extract a detection with 5.7σ‐confidence from the same data. We can resolve the tension between high and low PH3 abundance values by noticing that the former are from "mornings" in Venus' atmosphere and the latter from "evenings." Sunlight reduces the amount of phosphine in Earth's atmosphere by an order of magnitude, so similarly on Venus, we might expect lower abundances in data taken when the part of the atmosphere observed has passed through sunlight. If the six available data sets can be reconciled in this way, further modeling of possible sources of PH3 (e.g., volcanic, disequilibrium chemistry, extant life) seem worthwhile. Key Points: We recover Venusian phosphine in SOFIA spectra by reducing contaminating signals; the PH3 abundance is ∼3 part‐per billion (ppb)Six recoveries/limits show PH3 depleting between clouds and mesosphere, which would require an unknown re‐formation process or extra sourceRecoveries and upper limits can instead be reconciled by PH3 photolysis, as high/low abundances correspond to Venusian mornings/evenings [ABSTRACT FROM AUTHOR]

Aging results from the accumulation of molecular damage that impairs normal biochemical processes. We previously reported that age‐linked damage to amino acid sequence NGR (Asn‐Gly‐Arg) results in "gain‐of‐function" conformational switching to isoDGR (isoAsp‐Gly‐Arg). This integrin‐binding motif activates leukocytes and promotes chronic inflammation, which are characteristic features of age‐linked cardiovascular disorders. We now report that anti‐isoDGR immunotherapy mitigates lifespan reduction of Pcmt1−/− mouse. We observed extensive accumulation of isoDGR and inflammatory cytokine expression in multiple tissues from Pcmt1−/− and naturally aged WT animals, which could also be induced via injection of isoDGR‐modified plasma proteins or synthetic peptides into young WT animals. However, weekly injection of anti‐isoDGR mAb (1 mg/kg) was sufficient to significantly reduce isoDGR‐protein levels in body tissues, decreased pro‐inflammatory cytokine concentrations in blood plasma, improved cognition/coordination metrics, and extended the average lifespan of Pcmt1−/− mice. Mechanistically, isoDGR‐mAb mediated immune clearance of damaged isoDGR‐proteins via antibody‐dependent cellular phagocytosis (ADCP). These results indicate that immunotherapy targeting age‐linked protein damage may represent an effective intervention strategy in a range of human degenerative disorders. Synopsis: Anti‐isoDGR immunotherapy enhances the healthspan of naturally aged mice and extends the lifespan of Pcmt1 KO mice by reducing chronic inflammation. The health benefit is mediated by immune clearance of damaged proteins by antibody‐dependent cellular phagocytosis (ADCP). Age‐linked isoDGR protein damage induces chronic inflammation and tissue degeneration.The isoDGR triggered pathology is mitigated by anti‐isoDGR immunotherapy.The treatment decreases isoDGR‐protein levels, lowers pro‐inflammatory cytokines, increase body weight, improves cognition, and extends lifespan in Pcmt1 KO mice.The immunotherapy clears damaged isoDGR‐proteins through antibody‐dependent cellular phagocytosis. [ABSTRACT FROM AUTHOR]

Plant growth is influenced by interactions with neighbouring plants. The strength and direction of the cumulative neighbourhood effect on growth can depend on neighbour properties, such as their abundance, size and proximity, as well as the degree of similarity between interacting plants and their traits, which can be captured by the species identity of neighbours. Such interactions are also influenced by the local environmental conditions that are largely determined by climate. Because neighbour and climatic effects are typically explored in isolation, particularly in long‐lived species such as trees, it is unclear how the impacts of neighbours on plant growth shift in response to temporal variation in climatic conditions.Here, we explored how neighbouring plants impact the annual growth of two eucalypts, Eucalyptus delegatensis and Eucalyptus regnans, over three growing seasons in an experimental forest in south‐east Tasmania, Australia. We assessed whether eucalypt growth rates could be described by the number, size, proximity, and species identity of neighbours, and how the strength of this effect was influenced by the growing season climatic conditions.We found that climate and neighbouring plants had an interactive impact on eucalypt growth. Neighbours had a consistent, competitive effect on the growth of both eucalypts in all three growing seasons which was strongly related to the cumulative neighbourhood biomass. The identity of neighbours was important in determining E. regnans growth only, whereby distinguishing neighbours according to functional group best described growth. Over all three growing seasons, we predicted that, on average, neighbours reduced E. delegatensis and E. regnans mean annual growth by 60.5% and 48.4%, respectively. However, the strength of the competitive effect of neighbours on eucalypt growth was related to growing season climate, being strongest when conditions were hot and dry and weakest in cool, wet conditions.Synthesis: Given the consistent results observed in two co‐occurring eucalypts, our findings suggest that drier and hotter climatic conditions increase the strength of competitive effects on tree growth. This has implications for future forest productivity given projected increased temperatures and variation in rainfall patterns globally. [ABSTRACT FROM AUTHOR]

Background: Dermal fillers have created a multi‐billion‐dollar industry. They are the second most popular form of injectable, as they primarily address volume loss, augmentation, and provide immediate results. The most popular form includes hyaluronic acid‐based fillers, however, alternatives exist. Objective: To create clinical charts to help with filler selection, injection, and addressing common complications. Methods: The current literature and expert opinions form our two senior authors were used to create a numerical and color‐coded chart based on G‐prime for filler selection, as well as an anatomical table with current recommendations and pearls. We have also included a safety table with current clinical recommendation to deal with common filler‐related complications. Conclusion: Fillers are a safe and reliable method to achieve augmentation. Filler selection in various anatomical planes plays a significant role in achieving favorable results. [ABSTRACT FROM AUTHOR]

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Osteoporosis and fractures severely impact the elderly population. Polygenic risk scores for bone mineral density have demonstrated potential clinical utility. However, the value of rare genetic determinants in risk prediction has not been assessed. With whole‐exome sequencing data from 436,824 UK Biobank participants, we assigned White British ancestry individuals into a training data set (n = 317,434) and a test data set (n = 74,825). In the training data set, we developed a common variant‐based polygenic risk score for heel ultrasound speed of sound (SOS). Next, we performed burden testing to identify genes harboring rare determinants of bone mineral density, targeting influential rare variants with predicted high deleteriousness. We constructed a genetic risk score, called ggSOS, to incorporate influential rare variants in significant gene burden masks into the common variant‐based polygenic risk score. We assessed the predictive performance of ggSOS in the White British test data set, as well as in populations of non‐White British European (n = 18,885), African (n = 7165), East Asian (n = 2236), South Asian (n = 9829), and other admixed (n = 1481) ancestries. Twelve genes in pivotal regulatory pathways of bone homeostasis harbored influential rare variants associated with SOS (p < 5.5 × 10−7), including AHNAK, BMP5, CYP19A1, FAM20A, FBXW5, KDM5B, KREMEN1, LGR4, LRP5, SMAD6, SOST, and WNT1. Among 4013 (5.4%) individuals in the test data set carrying these variants, a one standard deviation decrease in ggSOS was associated with 1.35‐fold (95% confidence interval [CI] 1.16–1.57) increased hazard of major osteoporotic fracture. However, compared with a common variant‐based polygenic risk score (C‐index = 0.641), ggSOS had only marginally improved prediction accuracy in identifying at‐risk individuals (C‐index = 0.644), with overlapping confidence intervals. Similarly, ggSOS did not demonstrate substantially improved predictive performance in non‐European ancestry populations. In summary, modeling the effects of rare genetic determinants may assist polygenic prediction of fracture risk among carriers of influential rare variants. Nonetheless, improved clinical utility is not guaranteed for population‐level risk screening. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

Fire‐dependent savanna provides key habitat for butterflies globally, but we know little about how fire regimes, including fire frequency and season, affect them. These impacts are likely to be primarily indirect, through changes in overall habitat structure, the abundance of larval host plants, and/or the provision of nectar resources for adults. We examined the relationships among fire regime, butterfly abundance and diversity, and vegetation structure and floral resources within a long‐term fire experiment near Darwin in the Australian monsoon tropics. We surveyed butterflies and floral resources throughout the 2019–2020 wet season in three replicate plots of each of six experimental treatments that had been operating for 15 years. All plots subject to fire had been burned in the previous dry season. We observed 24 butterfly species and 280 individuals representing all five butterfly families found in Northern Australia. Butterfly abundance was highest under early dry‐season (June) fire regimes (mean = 11.9 individuals per plot survey) compared with a late dry‐season (October) regime (mean = 6.7) and in the long‐term absence of fire (mean = 5.3), and this was correlated with the abundance of floral resources. The distribution of butterflies was also highly associated with floral resources within plots regardless of fire treatment. Butterfly species richness was significantly higher in early dry‐season (mean = 6.8) compared with unburned (mean = 3.3) plots but did not differ between early and late dry‐season (mean = 4.7) plots. Butterfly and floral diversity were similar across all early dry‐season fire treatments regardless of whether they had been burned every 1, 2, 3, or 5 years. Our finding that early dry‐season burning promotes butterfly diversity and abundance by increasing the supply of nectar resources has important implications for biodiversity management more broadly, given that nectar is a critical resource for many animal taxa. [ABSTRACT FROM AUTHOR]