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Abstract Objectives (1) To plot the trajectory of humoral and cellular immune responses to the primary (two‐dose) COVID‐19 mRNA series and the third/booster dose in B‐cell‐depleted multiple sclerosis (MS) patients up to 2 years post‐vaccination; (2) to identify predictors of immune responses to vaccination; and (3) to assess the impact of intercurrent COVID‐19 infections on SARS CoV‐2‐specific immunity. Methods Sixty ocrelizumab‐treated MS patients were enrolled from NYU (New York) and University of Colorado (Anschutz) MS Centers. Samples were collected pre‐vaccination, and then 4, 12, 24, and 48 weeks post‐primary series, and 4, 12, 24, and 48 weeks post‐booster. Binding anti‐Spike antibody responses were assessed with multiplex bead‐based immunoassay (MBI) and electrochemiluminescence (Elecsys®, Roche Diagnostics), and neutralizing antibody responses with live‐virus immunofluorescence‐based microneutralization assay. Spike‐specific cellular responses were assessed with IFNγ/IL‐2 ELISpot (Invitrogen) and, in a subset, by sequencing complementarity determining regions (CDR)‐3 within T‐cell receptors (Adaptive Biotechnologies). A linear mixed‐effect model was used to compare antibody and cytokine levels across time points. Multivariate analyses identified predictors of immune responses. Results The primary vaccination induced an 11‐ to 208‐fold increase in binding and neutralizing antibody levels and a 3‐ to 4‐fold increase in IFNγ/IL‐2 responses, followed by a modest decline in antibody but not cytokine responses. Booster dose induced a further 3‐ to 5‐fold increase in binding antibodies and 4‐ to 5‐fold increase in IFNγ/IL‐2, which were maintained for up to 1 year. Infections had a variable impact on immunity. Interpretation Humoral and cellular benefits of COVID‐19 vaccination in B‐cell‐depleted MS patients were sustained for up to 2 years when booster doses were administered.

Abstract Background Chronic hand dermatitis (CHD) has suboptimal treatments and a negative impact on quality of life (QoL). Topical ruxolitinib, a JAK1/JAK2 inhibitor, is approved for vitiligo and mild‐to‐moderate atopic dermatitis, but has not previously been studied specifically for CHD. Objectives Evaluate the impact of ruxolitinib in CHD. Methods A 12‐week, investigator‐initiated, open‐label trial evaluated ruxolitinib 1.5% in 15 adults with recalcitrant moderate‐to‐severe CHD. Primary outcomes included the proportion of patients: (1) achieving an Investigator Global Assessment (IGA) treatment success (0 or 1 score with a two‐step improvement) (2) a Hand Eczema Severity Index (HECSI)‐75 improvement at 12 weeks. Additional outcomes: clinical improvement at 4 and 8 weeks, improvement in itch (Numerical Rating Scale [NRS]) and QoL outcomes (i.e., Dermatology Life Quality Index [DLQI] and Skindex‐Mini). Results At 12 weeks, 13/15 participants (86%) achieved a HECSI‐75, 12/15 participants (80%) had a two‐point reduction in IGA and 8/15 participants (53%) achieved an IGA treatment success. Both atopic dermatitis (AD; n = 7) and non‐AD (n = 8) CHD participants had clinical improvement in HECSI at 12 weeks (p

Abstract Pain can be defined as an unpleasant sensory and emotional experience associated with or resembling that associated with actual or potential tissue damage. Though consistent with this definition, different types of pain result in different behavioural and psychophysiological responses. For example, the transient, non‐threatening, acute muscle pain element of exercise‐induced pain (EIP) is entirely different from other pain types like delayed onset muscle soreness, muscular injury or chronic pain. However, studies often conflate the definitions or assume parity between distinct pain types. Consequently, the mechanisms through which pain might impact exercise behaviour across different pain subcategories may be incorrectly assumed, which could lead to interventions or recommendations that are inappropriate. Therefore, this review aims to distinguish EIP from other subcategories of pain according to their aetiologies and characteristics, thereby providing an updated conceptual and operational definition of EIP. Secondly, the review will discuss the experimental pain models currently used across several research domains and their relevance to EIP with a focus on the neuro‐psychophysiological mechanisms of EIP and its effect on exercise behaviour and performance. Finally, the review will examine potential interventions to cope with the impact of EIP and support wider exercise benefits. Highlights What is the topic of this review? Considerations for future research focusing on exercise‐induced pain within endurance exercise settings. What advances does it highlight? An updated appraisal and guide of research concerning exercise‐induced pain and its impact on endurance task behaviour, particularly with reference to the aetiology, measurement, and manipulation of exercise‐induced pain.

Societal Impact Statement Society is increasingly concerned over the environmental impact of diets. Much of this concern is over the environmentally destructive nature of meat production, especially beef and especially in the Amazon. This article aims to understand the production of beef in Brazil through the understudied perspective of forage grasses. In doing so, the article traces who was involved in the importation and improvement of forage grasses in Brazil, why they were involved, and what the consequences of their actions were. By centering forage grasses, we can better understand the potential consequences of seemingly unimportant plant breeding efforts. Summary Beef is viewed by many as one of the more environmentally destructive foods today. Whether it is deforestation in the Amazon or concentrated feedlots, the rancher and the cow have come to epitomize the dangers of a global industrial food system. This article looks at the industrialization of beef cattle from another angle, a bit closer to the ground. It looks at the role and circulation of plants and plant breeders in the expansion of beef cattle in the Brazilian tropics. The article draws on documents collected from the institutional archives of the Brazilian Agricultural Research Corporation, known by its Portuguese acronym Embrapa and the Rockefeller Archive Center. Additional archival documents were acquired by a personal contact. Embrapa was established in 1973, but its archives contain documents from Brazilian agricultural research agencies from as far back as 1952. Documents from the Rockefeller Archive Center include research bulletins and reports from Nelson Rockefeller's IBEC Research Institute (IRI), which conducted research on forage grasses from the 1950s until the 1970s. The article puts forth the argument that imported and improved forage grasses made large‐scale cattle ranching environmentally viable and economically profitable in Brazil. One type of grass in particular, Brachiaria, was central in propelling Brazil as the world's largest producer of beef and underpinning perhaps the most environmentally and socially destructive cattle ranching system in the world. Brachiaria was a key biological and technological input to further entrench longstanding structural inequalities of land ownership. One of the key conclusions of this article is that perspectives from the margins can be illustrative of how seemingly unimportant research (forage grass breeding) can have massive consequences as part of a broader socio‐environmental system.

Abstract Objective Multifocal motor neuropathy is a rare chronic immune‐mediated neuropathy with impaired grip strength representing a common symptom. While intravenous immunoglobulin G is an effective treatment for the disease, significant variation in treatment response has been observed but not well understood. This analysis characterized dose–exposure–response relationships in multifocal motor neuropathy, using grip strength as a clinical efficacy measure. Methods Serum immunoglobulin G trough concentrations and grip strength data for the more affected hand from a Phase 3, randomized, double‐blind, placebo‐controlled, crossover trial of intravenous immunoglobulin 10% in 44 patients with multifocal motor neuropathy (NCT00666263) were used to develop a population pharmacokinetic–pharmacodynamic model. Results The model adequately described the observed pharmacokinetic and pharmacodynamic data and relationships between intravenous immunoglobulin 10% dose, serum immunoglobulin G trough levels, grip strength, and inter‐patient variabilities in multifocal motor neuropathy. Model‐based simulations for various dosing regimens (0.4–2.0 g/kg every 2–4 weeks) indicated that ≥1.6 g/kg/month would achieve clinically meaningful improvements in grip strength (≥4 kg) in ≥70% of patients. More frequent dosing at an equivalent monthly dose led to a more consistent response in grip strength. Furthermore, splitting the dose over multiple days for high doses (>1 g/kg) did not impact grip strength. Interpretation These findings suggest that the majority of patients with multifocal motor neuropathy would respond rapidly to intravenous immunoglobulin 10% with a range of dosing regimens. Shorter dosing intervals may avoid the diminishing response seen with longer dosing intervals. Dose‐splitting provided similar outcomes while offering flexibility and convenience.

Abstract Background We aim to determine the multiethnic patterns of the prevalence and associated factors of poor muscle health and its associated components in older Chinese, Malays, and Indian Asian adults. Methods We included 2199 participants (mean age ± SD: 72.9 ± 8.3 years; 54.3% female) from the baseline assessment of the Population Health and Eye Disease Profile in Elderly Singaporeans (PIONEER; 2017–2022) cohort study. Poor muscle health was defined as the presence of either low muscle mass (DEXA), or low muscle strength (handgrip strength), or low physical performance (gait speed). Its components include poor muscle function (low muscle strength and/or low physical performance without low muscle mass), pre‐sarcopenia (low muscle mass only), and any sarcopenia (low muscle mass with low muscle strength and/or low physical performance). Sociodemographic, clinical, and lifestyle factors were assessed using biochemistry, clinical tests, and validated questionnaires. Regression models were utilized to evaluate the independent risk factors of poor muscle health and its components. Results The national census‐adjusted prevalence of poor muscle health (88%) was similar across the three ethnic groups. However, Chinese individuals had higher prevalence of pre‐sarcopenia and any sarcopenia, and a lower prevalence of poor muscle function compared with Indians or Malays. We observed ethnic differences in modifiable risk factors (low physical activity, diabetes, osteoporosis, and obesity) of poor muscle health and its components. Although obesity was protective of pre‐sarcopenia (RRR = 0.19, 95% CI: 0.11, 0.36) and any sarcopenia (RRR = 0.29, 95% CI: 0.18, 0.47) in the overall population and across ethnic groups, it was associated with 1.7 times (95% CI: 1.07, 2.67) the likelihood of poor muscle function in the entire population. Conclusions Almost 90% of community dwelling Singaporean aged ≥60 years have poor muscle health across the three ethnic groups with ethnic disparities in modifiable risk factors, highlighting an urgent need for community‐wide targeted interventions to promote muscle health.

Abstract Aims The study aims to investigate exercise‐limiting factors in hypertrophic cardiomyopathy (HCM) using combined stress echocardiography and cardiopulmonary exercise test. Methods and results A symptom‐limited ramp bicycle exercise test was performed in the semi‐supine position on a tilting dedicated ergometer. Echocardiographic images were obtained concurrently with gas exchange measurements along predefined stages of exercise. Oxygen extraction was calculated using the Fick equation at each activity level. Thirty‐six HCM patients (mean age 67 ± 6 years, 72% men, 18 obstructive HCM) were compared with age and sex‐matched 29 controls. At rest, compared with controls, E/E′ ratio (6.26 ± 2.3 vs. 14 ± 2.5, P

Abstract Incorporating automation into wind turbine blade manufacturing is important for reducing costs to meet current offshore wind energy production goals in the United States. This work proposes a process for automating three operations in wind blade manufacturing: trimming to remove flashing left over after bonding two blade skins together, grinding to produce a desired leading‐edge shape, and sanding to prepare the blade for bonding overlamination or adding paint to the surface. The majority of this work focuses on the toolpath generation. The algorithms were tested on a 5‐m blade section, and the results were analyzed in terms of operation speed and accuracy. Finally, future work is discussed to improve the performance of the system.

Abstract The hormonal changes in women influence creatine dynamics, emphasizing its potential importance during menstruation, pregnancy, postpartum, menopause, and postmenopause. Yet, limited research explores creatine's impact on female reproductive health at the population level. Our study investigated the relationship between dietary creatine intake and reproductive health indices in US women using data from the 2017–2020 National Health and Nutrition Examination Survey (NHANES). We extracted a dataset containing females aged 12 years and above who provided details about their reproductive health and dietary habits. Daily creatine intake was quantified as a relative amount (mg per kg body mass) and did not include creatine from dietary supplements and pharmacological agents. A daily requirement for dietary creatine for healthy women was employed to classify respondents into two separate subpopulations: (1) suboptimal intake of creatine (

Abstract Limb immobilization causes rapid declines in muscle strength and mass. Given the role of the nervous system in immobilization‐induced weakness, targeted interventions may be able to preserve muscle strength, but not mass, and vice versa. The purpose of this study was to assess the effects of two distinct interventions during 1 week of knee joint immobilization on muscle strength (isometric and concentric isokinetic peak torque), mass (bioimpedance spectroscopy and ultrasonography), and neuromuscular function (transcranial magnetic stimulation and interpolated twitch technique). Thirty‐nine healthy, college‐aged adults (21 males, 18 females) were randomized into one of four groups: immobilization only (n = 9), immobilization + action observation/mental imagery (AOMI) (n = 10), immobilization + neuromuscular electrical stimulation (NMES) (n = 12), or control group (n = 8). The AOMI group performed daily video observation and mental imagery of knee extensions. The NMES group performed twice daily stimulation of the quadriceps femoris. Based on observed effect sizes, it appears that AOMI shows promise as a means of preserving voluntary strength, which may be modulated by neural adaptations. Strength increased from PRE to POST in the AOMI group, with +7.2% (Cohen's d = 1.018) increase in concentric isokinetic peak torque at 30°/s. However, NMES did not preserve muscle mass. Though preliminary, our findings highlight the specific nature of clinical interventions and suggest that muscle strength can be independently targeted during rehabilitation. This study was prospectively registered: ClinicalTrials.gov NCT05072652.

Abstract In partial onset epilepsy, seizures arise focally in the brain and often propagate. Patients frequently become refractory to medical management, leaving neurosurgery, which can cause neurologic deficits, as a primary treatment. In the cortex, focal seizures spread through horizontal connections in layers II/III, suggesting that severing these connections can block seizures while preserving function. Focal neocortical epilepsy is induced in mice, sub‐surface cuts are created surrounding the seizure focus using tightly‐focused femtosecond laser pulses, and electrophysiological recordings are acquired at multiple locations for 3–12 months. Cuts reduced seizure frequency in most animals by 87%, and only 5% of remaining seizures propagated to the distant electrodes, compared to 80% in control animals. These cuts produced a modest decrease in cortical blood flow that recovered and left a ≈20‐µm wide scar with minimal collateral damage. When placed over the motor cortex, cuts do not cause notable deficits in a skilled reaching task, suggesting they hold promise as a novel neurosurgical approach for intractable focal cortical epilepsy.

Abstract Antarctic moss beds are sensitive to climatic conditions, and both their survival and community composition are particularly influenced by the availability of liquid water over summer. As Antarctic regions increasingly face climate pressures (e.g., changing hydrology and heat waves), advancing capabilities to efficiently and non‐destructively monitor water content in moss communities becomes a key research priority. Because of the complexity induced by multiple micro‐climatic drivers and its fragility, tracking the evolution and responses of moss bed moisture requires monitoring methods that are non‐intrusive, efficient, and spatially significant, such as the use of unoccupied aerial systems (UAS). In this study, we combine a multi‐species drying laboratory experiment with short‐wave infrared (SWIR) spectroscopy analyses to first develop a Random Forest regression Model (RFM) capable of predicting Antarctic moss turf water content (~5% error). The RFM was then applied to UAS‐borne SWIR imaging data (900–1700 nm,

Abstract Young individuals with post‐traumatic stress disorder (PTSD) display peripheral vascular and autonomic nervous system dysfunction, two factors potentially stemming from a redox imbalance. It is currently unclear if these aforementioned factors, observed at rest, alter peripheral haemodynamic responses to exercise in this population. This study examined haemodynamic responses to handgrip exercise in young individuals with PTSD following acute antioxidant (AO) supplementation. Thirteen young individuals with PTSD (age 23 ± 3 years), and 13 age‐ and sex‐matched controls (CTRL) participated in the study. Exercise‐induced changes to arm blood flow (BF), mean arterial pressure (MAP) and vascular conductance (VC) were evaluated across two workloads of rhythmic handgrip exercise (3 and 6 kg). The PTSD group participated in two visits, consuming either a placebo (PL) or AO prior to their visits. The PTSD group demonstrated significantly lower VC (P = 0.04) across all exercise workloads (vs. CTRL), which was significantly improved following AO supplementation. In the PTSD group, AO supplementation improved VC in participants possessing the lowest VC responses to handgrip exercise, with AO supplementation significantly improving VC responses (3 and 6 kg: P

Abstract Introduction Although prostate magnetic resonance imaging (MRI) is commonly used in the diagnosis, staging and active surveillance of prostate cancer, little is known about patient perspectives on MRI. Methods We performed a qualitative study consisting of in‐depth, semi‐structured interviews of patients with low‐ and intermediate‐risk prostate cancer managed with active surveillance. Interviews focused on experiences with and knowledge of prostate MRI and MRI‐ultrasound fusion biopsy during active surveillance. We purposively sampled patients who received prostate MRI as part of their clinical care, conducted interviews until reaching thematic saturation and performed conventional content analysis to analyse data. Results Twenty patients aged 51–79 years (mean = 68 years) participated in the study. At diagnosis, 17 (85%) had a Gleason grade group 1, and three (15%) had a grade group 2 tumour. Overall, participants viewed prostate MRI as a valuable tool that accurately localizes and monitors prostate cancer over time, and they considered prostate MRI central to active surveillance monitoring. We identified five thematic categories related to MRI use: (1) the experiential aspects of undergoing an MRI scan; (2) the experience of visualizing one's own prostate and prostate cancer; (3) adequacy of provider explanations of MRI results; (4) confidence in prostate MRI in decision‐making; and (5) the role of prostate MRI in longitudinal follow‐up, including an interest in using MRI to modify the timing of, or replace, prostate biopsy. Conclusion Patients value prostate MRI as a tool that enhances their confidence in the initial diagnosis and monitoring of prostate cancer. This work can inform future studies to optimize patient experience, education and counselling during active surveillance for prostate cancer.

Dopamine (DA) acts in various key neurological and physiological processes as both a neurotransmitter and circulating hormone. Over the past several decades, the DA signaling network has been shown to regulate the progression of several types of solid tumors, and considerable evidence has shown it is a druggable pathway in the cancer cell context. However, the specific activity and effect of these pathway components appears to be tissue‐type and cell‐context‐dependent. In the present study, expression and methylation of dopamine receptor D1 (DRD1) were measured using RNA sequencing (RNAseq) and reverse transcription polymerase chain reaction (RT‐PCR) in non‐small cell lung cancer (NSCLC) samples, and validated using publicly available datasets, including The Cancer Genome Atlas (TCGA). In vitro and in vivo functional experiments were performed for cell proliferation and tumor growth, respectively. Mechanistic analyses of the transcriptome and kinome in DRD1‐modulated cells informed further experiments, which characterized the effects on the epidermal growth factor receptor (EGFR) pathway and programmed cell death 1 ligand 1 (PD‐L1) proteins. Through these experiments, we identified the DRD1 gene as a negative regulator of disease progression in NSCLC. We show that DRD1, as well as other DA pathway components, are expressed in normal human lung tissue, and that loss of DRD1 expression through promoter hypermethylation is a common feature in NSCLC patients and is associated with worse survival. At the cellular level, DRD1 affects proliferation by inhibiting the activation of EGFR and mitogen‐activated protein kinase 1/2 (ERK1/2). Interestingly, we also found that DRD1 regulates the expression of PD‐L1 in lung cancer cells. Taken together, these results suggest that DRD1 methylation may constitute a biomarker of poor prognosis in NSCLC patients while other components of this pathway could be targeted to improve response to EGFR‐ and PD‐L1‐targeted therapies.

Abstract Defaunation and extinction undermine the resilience and functioning of ecological communities and ecosystems. Relative to other disturbances, overexploitation for the global wildlife trade presents a unique case of trait‐based selection, as demand for specific individuals is often tied to unique morphological or aesthetic traits desired by consumers (‘market traits’). Because evolutionary history leads to species that share both market and functional traits, we posit that non‐random patterns of exploitation will result in non‐random loss of functional diversity. We applied a trait‐based framework to the global songbird trade for 4616 species, 148 of which are plausibly threatened by the trade. We quantified select market traits, such as unique coloration and song quality, and ecological traits related to body size, diet, and foraging strategy to assess whether the trade disproportionately threatens particular functional groups. We additionally looked for patterns of association between market traits and functional traits to assess whether selection on certain market traits could drive selection on associated functional traits. We found that overexploited birds are a distinct functional subset of the global songbird pool, with the trade disproportionately threatening large bodied, frugivorous, and seed eating birds. Across all songbirds, there were multiple non‐random associations between market traits and functional traits, with the strongest associations observed among trade‐threatened birds; this was consistent with our theory that consumer‐driven selection on market traits could theoretically result in selection on functional traits. However, there was mixed evidence for this hypothesis at a global scale, suggesting that disproportionate threat to functional diversity may be more likely in regions where there is heavy demand for associated market traits. Policy implications. Our results highlight the need for increased focus on the mechanistic drivers of trait‐based selection on the consumer side of wildlife trade, and how patterns of overexploitation can systematically affect ecological communities and ecosystem services. Read the free Plain Language Summary for this article on the Journal blog.

Abstract This study compared the acute hypoalgesic and neurophysiological responses to low‐load resistance exercise with and without blood flow restriction (BFR), and free‐flow, high‐load exercise. Participants performed four experimental conditions where they completed baseline measures of pain pressure threshold (PPT), maximum voluntary force (MVF) with peripheral nerve stimulation to determine central and peripheral fatigue. Corticospinal excitability (CSE), corticospinal inhibition and short interval intracortical inhibition (SICI) were estimated with transcranial magnetic stimulation. Participants then performed low‐load leg press exercise at 30% of one‐repetition maximum (LL); low‐load leg press with BFR at 40% (BFR40) or 80% (BFR80) of limb occlusion pressure; or high‐load leg press of four sets of 10 repetitions at 70% one‐repetition maximum (HL). Measurements were repeated at 5, 45 min and 24 h post‐exercise. There were no differences in CSE or SICI between conditions (all P > 0.05); however, corticospinal inhibition was reduced to a greater extent (11%–14%) in all low‐load conditions compared to HL (P 0.05). In summary, low‐load BFR resistance exercise does not induce different acute neurophysiological responses to low‐load, free‐flow exercise but it does promote a greater degree of hypoalgesia and reduces corticospinal inhibition more than high‐load exercise, making it a useful rehabilitation tool. The changes in neurophysiology following exercise were not related to changes in PPT.

Abstract Objective In parallel to standard vagus nerve stimulation (VNS), microburst stimulation delivery has been developed. We evaluated the fMRI‐related signal changes associated with standard and optimized microburst stimulation in a proof‐of‐concept study (NCT03446664). Methods Twenty‐nine drug‐resistant epilepsy patients were prospectively implanted with VNS. Three 3T fMRI scans were collected 2 weeks postimplantation. The maximum tolerated VNS intensity was determined prior to each scan starting at 0.125 mA with 0.125 mA increments. FMRI scans were block‐design with alternating 30 sec stimulation [ON] and 30 sec no stimulation [OFF]: Scan 1 utilized standard VNS and Scan 3 optimized microburst parameters to determine target settings. Semi‐automated on‐site fMRI data processing utilized ON–OFF block modeling to determine VNS‐related fMRI activation per stimulation setting. Anatomical thalamic mask was used to derive highest mean thalamic t‐value for determination of microburst stimulation parameters. Paired t‐tests corrected at P

Abstract Objective Most families with heritable neuromuscular disorders do not receive a molecular diagnosis. Here we evaluate diagnostic utility of exome, genome, RNA sequencing, and protein studies and provide evidence‐based recommendations for their integration into practice. Methods In total, 247 families with suspected monogenic neuromuscular disorders who remained without a genetic diagnosis after standard diagnostic investigations underwent research‐led massively parallel sequencing: neuromuscular disorder gene panel, exome, genome, and/or RNA sequencing to identify causal variants. Protein and RNA studies were also deployed when required. Results Integration of exome sequencing and auxiliary genome, RNA and/or protein studies identified causal or likely causal variants in 62% (152 out of 247) of families. Exome sequencing alone informed 55% (83 out of 152) of diagnoses, with remaining diagnoses (45%; 69 out of 152) requiring genome sequencing, RNA and/or protein studies to identify variants and/or support pathogenicity. Arrestingly, novel disease genes accounted for

Societal Impact Statement Plants and agricultural practices are an integral part of human food systems and well‐being. Here, an example of an ethnobotanical research approach is provided to increase our understanding of the relationship between plants and human activities in Madagascar, where the agricultural sector is the local economy basis. This research examines weeds of the Poaceae family, assessing their recognition and societal impacts, and quantifying farmers' perception of the Poaceae weed's status in cropping systems. A better understanding of farmers' weed knowledge will strengthen our ability to inclusively support rural highland Malagasy food systems, incorporating science with traditional knowledge. Summary Research on the perceptions and knowledge of Poaceae weeds was conducted in three areas of Madagascar's central highlands: Itremo massif, Ambohidray village and Vakinankaratra region. This work aims to identify the best‐known species and understand their roles in crop and livestock systems. Additionally, it presents detailed data on Digitaria species. The approach was based on field surveys and farmer's interviews, with plant voucher specimens and photographs to facilitate identification. Relative frequency of citations, confidence interval, and use values indexes were calculated to assess cultural significance. We carried out 111 interviews, where 87 taxa were mentioned, of which 51 are Poaceae, including 11 Digitaria species. Farmers classify the Poaceae weeds in three ways: their impacts on agricultural activities, use category and vegetative growth patterns, the latter especially significant for Digitaria. Locally common grasses are perceived as weeds when they are abundant and cause yield loss. The most damaging species is Digitaria humbertii, confirmed by half of the interviews. More than 40% of the farmers use Poaceae weeds in composting, more than 20% as fodder, and more than 8% as medicine. Overall, 67% of the species mentioned are judged useful. The diversity of useful species and the associated indigenous knowledge is important to the local communities, but, weeds are still perceived as negative generally. The Poaceae are overall neglected in Malagasy ethnobotany, and an in‐depth analysis of farmer knowledge is needed. The data obtained will be useful for future studies and the conservation of agrobiodiversity, especially endemic species that are not widely known.

Abstract Objective To determine the prevalence of neuroimaging abnormalities in individuals with Down syndrome regression disorder (DSRD) and evaluate if neuroimaging abnormalities were predictive of therapeutic responses. Methods A multicenter, retrospective, case–control study which reviewed neuroimaging studies of individuals with DSRD and compared them to a control cohort of individuals with Down syndrome (DS) alone was performed. Individuals aged 10–30 years and meeting international consensus criteria for DSRD were included. The presence of T1, T2/FLAIR, and SWI signal abnormalities was reviewed. Response rates to various therapies, including immunotherapy, were evaluated in the presence of neuroimaging abnormalities. Results In total, 74 individuals (35%) had either T2/FLAIR and/or SWI signal abnormality compared to 14 individuals (12%) without DSRD (p

Objective Acute visual impairment is the most feared complication of giant cell arteritis (GCA) but is challenging to predict. Magnetic resonance imaging (MRI) evaluates orbital pathology not visualized by an ophthalmologic examination. This study combined orbital and cranial vessel wall MRI to assess both orbital and cranial disease activity in patients with GCA, including patients without visual symptoms. Methods Patients with suspected active GCA who underwent orbital and cranial vessel wall MRI were included. In 14 patients, repeat imaging over 12 months assessed sensitivity to change. Clinical diagnosis of ocular or nonocular GCA was determined by a rheumatologist and/or ophthalmologist. A radiologist masked to clinical data scored MRI enhancement of structures. Results Sixty‐four patients with suspected GCA were included: 25 (39%) received a clinical diagnosis of GCA, including 12 (19%) with ocular GCA. Orbital MRI enhancement was observed in 83% of patients with ocular GCA, 38% of patients with nonocular GCA, and 5% of patients with non‐GCA. MRI had strong diagnostic performance for both any GCA and ocular GCA. Combining MRI with a funduscopic examination reached 100% sensitivity for ocular GCA. MRI enhancement significantly decreased after treatment (P

Abstract Background Accumulating evidence has demonstrated that chronic tobacco smoking directly contributes to skeletal muscle dysfunction independent of its pathological impact to the cardiorespiratory systems. The mechanisms underlying tobacco smoke toxicity in skeletal muscle are not fully resolved. In this study, the role of the aryl hydrocarbon receptor (AHR), a transcription factor known to be activated with tobacco smoke, was investigated. Methods AHR related gene (mRNA) expression was quantified in skeletal muscle from adult controls and patients with chronic obstructive pulmonary disease (COPD), as well as mice with and without cigarette smoke exposure. Utilizing both skeletal muscle‐specific AHR knockout mice exposed to chronic repeated (5 days per week for 16 weeks) cigarette smoke and skeletal muscle‐specific expression of a constitutively active mutant AHR in healthy mice, a battery of assessments interrogating muscle size, contractile function, mitochondrial energetics, and RNA sequencing were employed. Results Skeletal muscle from COPD patients (N = 79, age = 67.0 ± 8.4 years) had higher levels of AHR (P = 0.0451) and CYP1B1 (P

Histone‐lysine N‐methyltransferase SETD2 (SETD2), the sole histone methyltransferase that catalyzes trimethylation of lysine 36 on histone H3 (H3K36me3), is often mutated in clear cell renal cell carcinoma (ccRCC). SETD2 mutation and/or loss of H3K36me3 is linked to metastasis and poor outcome in ccRCC patients. Epithelial‐to‐mesenchymal transition (EMT) is a major pathway that drives invasion and metastasis in various cancer types. Here, using novel kidney epithelial cell lines isogenic for SETD2, we discovered that SETD2 inactivation drives EMT and promotes migration, invasion, and stemness in a transforming growth factor‐beta‐independent manner. This newly identified EMT program is triggered in part through secreted factors, including cytokines and growth factors, and through transcriptional reprogramming. RNA‐seq and assay for transposase‐accessible chromatin sequencing uncovered key transcription factors upregulated upon SETD2 loss, including SOX2, POU2F2 (OCT2), and PRRX1, that could individually drive EMT and stemness phenotypes in SETD2 wild‐type (WT) cells. Public expression data from SETD2 WT/mutant ccRCC support the EMT transcriptional signatures derived from cell line models. In summary, our studies reveal that SETD2 is a key regulator of EMT phenotypes through cell‐intrinsic and cell‐extrinsic mechanisms that help explain the association between SETD2 loss and ccRCC metastasis.

Background Cardiovascular disease (CVD) and cancer frequently co‐occur due to shared risk factors such as obesity, which is linked to CVD and 14 cancer types. This study explores whether CVD pathophysiologies, combined with obesity, increase cancer risk, impacting clinical management. Methods and Results Data from the ARIC (Atherosclerosis Risk in Communities) study, spanning 28 years, were analyzed. The cohort included 5127 participants with incident CVD (myocardial infarction, stroke, heart failure, coronary heart disease), of whom 1511 developed a first primary cancer. Follow‐up began at CVD diagnosis after Visit 1. Obesity was assessed using body mass index, waist circumference, and waist‐to‐hip ratio. Incidence rate differences between obesity groups were adjusted for age, sex, and center, whereas the obesity–cancer association was estimated using Fine‐Gray regression adjusted for shared risk factors including smoking. Cancer incidence in obese individuals with CVD (body mass index: rate differences=226.6/100 000 person‐years) was higher than in those with normal weight. Although obesity was not linked to overall cancer after adjusting for shared risk factors, it was nominally associated with obesity‐related cancers. Specifically, women with CVD and obesity had increased obesity‐related cancer risk (body mass index: hazard ratio, 1.67 [95% CI, 1.17–2.31]). No significant associations were found in men, even after excluding prostate cancer. Conclusions This study suggests that obesity is linked to higher obesity‐related cancer risk in women with incident CVD, independent of shared risk factors. Further research is needed to eliminate residual confounding, understand sex differences, and explore how CVD pathophysiologies and obesity together influence cancer risk.

Background The treatment of severe aortic stenosis has evolved considerably since the introduction of transcatheter aortic valve replacement (TAVR), yet trends in complications for patients undergoing TAVR or surgical aortic valve replacement (SAVR) at a national level have yet to be evaluated. Methods and Results We performed a retrospective cohort study using Medicare data to evaluate temporal trends in complications among beneficiaries, aged ≥65 years, treated with elective isolated transfemoral TAVR or SAVR between 2012 and 2019. The study end point was the occurrence of a major complication (composite outcome) during index and up to 30 days after. Multivariable logistic regression was used to assess odds of complications for TAVR and SAVR, individually over time, and for TAVR versus SAVR, over time. The cohort included 211 212 patients (mean±SD age, 78.6±7.3 years; 45.0% women). Complication rates during index following elective isolated aortic valve replacement decreased from 49% in 2012 to 22% in 2019. These reductions were more pronounced for TAVR (41% to >19%, Δ=22%) than SAVR (51% to >47%, Δ=4%). After risk adjustment, the risk of any complication with TAVR was 47% (P

Abstract Introduction Men with African ancestry have the highest incidence and mortality rates of prostate cancer (PCa) worldwide. Methods This study aimed to identify differentially methylated genes between tumor vs. adjacent normal and aggressive vs. indolent PCa in 121 African American patients. Epigenome‐wide DNA methylation patterns in tumor DNA were assessed using the human Illumina Methylation EPIC V1 array. Results Around 5,139 differentially methylated CpG‐sites (q 0.2) were identified when comparing normal vs. tumor, with an overall trend of hypermethylation in prostate tumors. Multiple representative differentially methylated regions (DMRs), including immune‐related genes, such as CD40, Galectin3, OX40L, and STING, were detected in prostate tumors when compared to adjacent normal tissues. Based on an epigenetic clock model, we observed that tumors’ total number of stem cell divisions and the stem cell division rate were significantly higher than adjacent normal tissues. Regarding PCa aggressiveness, 2,061 differentially methylated CpG‐sites (q .05) were identified when the grade group (GG)1 was compared with GG4/5. Among these 2,061 CpG sites, 155 probes were consistently significant in more than one comparison. Among these genes, several immune system genes, such as COL18A1, S100A2, ITGA4, HLA‐C, and ADCYAP1, have previously been linked to tumor progression in PCa. Conclusion Several differentially methylated genes involved in immune‐oncologic pathways associated with disease risk or aggressiveness were identified. In addition, 261 African American‐specific differentially methylated genes related to the risk of PCa were identified. These results can shedlight on potential mechanisms contributing to PCa disparities in the African American Population.

Abstract Emerging fishing activity due to melting ice and poleward species distribution shifts in the rapidly‐warming Arctic Ocean challenges transboundary management and requires proactive governance. A 2021 moratorium on commercial fishing in the Arctic high seas provides a 16‐year runway for improved scientific understanding. Given substantial knowledge gaps, characterizing areas of highest uncertainty is a key first step. Marine ecosystem model ensembles that project future fish distributions could inform management of future Arctic fisheries, but Arctic‐specific variation has not yet been examined for global ensembles. We use the Fisheries and Marine Ecosystem Intercomparison Project ensemble driven by two Earth System Models (ESMs) under two Shared Socioeconomic Pathways (SSP1‐2.6 and SSP5‐8.5) to illustrate the current state of and uncertainty among biomass projections for the Arctic Ocean over the duration of the moratorium. The models generally project biomass increases in more northern Arctic ecosystems and decreases in southern ecosystems, but wide intra‐model variation exceeds projection means in most cases. The two ESMs show opposite trends for the main environmental drivers. Therefore, these projections are currently insufficient to inform policy actions. Investment in sustained monitoring and improving modeling capacity, especially for sea ice dynamics, is urgently needed. Concurrently, it will be necessary to develop frameworks for making precautionary decisions under continued uncertainty. We conclude that researchers should be transparent about uncertainty, presenting these model projections not as a source of scientific “answers,” but as bounding for plausible, policy‐relevant questions to assess trade‐offs and mitigate risks.

Abstract Piping plovers (Charadrius melodus sp.) rank among North America's most endangered shorebird species, facing compounding environmental challenges that reduce habitat availability and suppress recruitment and survival rates. Despite these challenges, research on the direct effects of climate variability and extremes on their breeding ecology remains limited. Here, we employ a spatiotemporal modelling approach to investigate how location, nest timing and weather conditions influence reproductive success rates in a small breeding population of C. m. melodus in Prince Edward Island (PEI), Canada from 2011 to 2023. Analysis of 40 years of monitoring records from a subset of nesting sites revealed that flooding and predation have been persistent sources of reproductive failures in this population, with unexplained losses increasing in recent years. Contrary to our hypotheses, our modelled results did not support a negative impact of extreme high temperatures and strong precipitation events on reproductive outcomes. Instead, we identified a positive effect of TMAX and no effect of strong precipitation, perhaps due to limited exposure to extreme high temperatures (>32°C) and context‐specific risks associated with precipitation‐induced flooding. However, trends in regional climate change are likely to increase exposure to—and the influence of—such factors in the near future. Our models also identified spatiotemporal variability in apparent hatch success over the study period, as well as worse hatch outcomes across popular beachgoing regions and for delayed nesting attempts. While our results offer preliminary insights into factors affecting breeding success in this population, further research will be imperative to enhance understanding of constraints on recruitment. To this end, we encourage the collection and analysis of additional time‐series data of prey populations, human activities, fine‐scale weather data and predator/flood risks associated with each nest on PEI.

Abstract The Great Lakes Region (GLR) of North America is at the intersection of multiple extratropical cyclone (ETC) tracks, and the region's cold‐season climate is heavily influenced by the large temperature gradients and intense precipitation associated with these cyclones. The goal of this study is to understand how ETCs are changing within a warming climate. Historical GLR cyclone characteristics from 1959 to 2021 are examined using a storm tracking algorithm and the ERA‐5 atmospheric reanalysis. Of the 886 cyclones identified, half are the large long‐track cyclones that are typically included in ETC studies, and half are smaller short‐track cyclones that, while not always considered in ETC studies, still have an important impact on the GLR with significant precipitation trends. While all cyclones exhibit strong interannual variability, storm trajectories appear to be migrating northward and, most notably, the cyclones are becoming warmer and wetter at a rate faster than the background climate.

Abstract Objective Existing behavioral weight management interventions produce clinically meaningful weight loss. The onset of the COVID‐19 pandemic led to the quick transition of such interventions from in‐person to virtual platforms. This provided a unique opportunity to compare engagement and outcomes for an in‐person versus virtually delivered weight management intervention. Methods A non‐randomized comparison of engagement and weight outcomes was performed between two cohorts who participated in a weight management intervention in person (N = 97) versus three who participated virtually via videoconference (N = 134). Various metrics of engagement were examined, including group class and individual phone call attendance and duration, and retention for weight assessments. Behavioral targets of daily caloric intake and step‐counts and the clinical weight outcome were explored. Results Cohorts (mean [standard deviation] age 47.3 (11.5), 67.1% women: 86.8% White) that participated virtually attended more group sessions (p

Abstract Objective Safe home tracheostomy care requires engagement and troubleshooting by patients, who may turn to online, AI‐generated information sources. This study assessed the quality of ChatGPT responses to such queries. Methods In this cross‐sectional study, ChatGPT was prompted with 10 hypothetical tracheostomy care questions in three domains (complication management, self‐care advice, and lifestyle adjustment). Responses were graded by four otolaryngologists for appropriateness, accuracy, and overall score. The readability of responses was evaluated using the Flesch Reading Ease (FRE) and Flesch–Kincaid Reading Grade Level (FKRGL). Descriptive statistics and ANOVA testing were performed with statistical significance set to p

ABSTRACT Background Health and social care regulators are organisations that seek to maintain public trust in professionals and protect the public from harmful practitioners. For example, they ensure that practitioners have the correct qualifications to practice and investigate any concerns raised about them. Serious concerns can result in a fitness to practise (FtP) hearing where a member of the public may be required to give evidence as a witness. Being a witness and being cross‐examined is known to often be traumatic, particularly for members of the public in criminal trials. There is some research evidence that registered professionals who are the subject of the proceedings may suffer mental ill health as result of the experience. But there is scant research that specifically explores the experiences of members of the public giving evidence in a FtP hearing. The regulator web pages are an important source of information for public witnesses to prepare themselves for a FtP hearing. Aim This study aimed to examine the publicly available information for public witnesses from the 13 health and social care regulators in the United Kingdom to evaluate the content, amount, type and format of information available and make recommendations about how regulators can improve these. Methods Regulator websites were searched during November 2021–February 2022 for information for the public on what happens after raising a concern with a regulator. Resources were downloaded and qualitative content analysis conducted. Our findings were validated by interviews (n = 7) with the public including people with experience of FtP and a focus group of the public (n = 5). Results One hundred and forty‐six resources (97 webpages and 25 public facing documents, 20 videos and 4 easy read documents) were found. Topics included screening and investigation, preparing for a hearing, during a hearing and after a hearing, and support for witnesses. Discussion and Conclusion We conclude that there are many deficiencies in the information content and its presentation for the public and some exemplars, such as the use of flowcharts and short videos to explain the FtP processes. Recommendations for practice take the form of a framework with three themes, (i) co‐production, (ii) preferred content and (iii) format. It may be used by regulators to enhance their support for members of the public as witnesses in FtP hearings. Public Contribution Our advisory group of people with lived experience of involvement as members of the public in FtP discussed the findings and contributed to the recommendations.

Abstract Applications for an antenna structure produced with additive manufacturing technology are numerous and promising. This study focuses explicitly on utilizing micro‐laser sintering (MLS) three‐dimensional (3D) printing technology to fabricate two rectangular horn antennas identical to a standard Pasternack® horn antenna, making the fabrication straightforward. The objective is to investigate how surface roughness affects antenna performance in a frequency range of 18 to 26.5 GHz. One antenna is polished and the other is left untouched, resulting in surface roughness of 4 and 6 µm, respectively, measured using a profilometer. Then, a vector network analyzer was used to assess their reflection coefficient, transmission characteristics, and radiation pattern and determine gains of 8.83 and 9.14 dBi for the polished and unpolished antennas, respectively. The study finds that both polished and unpolished antennas perform similarly, and their characteristics closely resembling simulated and standard antennas. Finally, the performance of the MLS‐printed metallic antennas is compared with horn antennas created using other 3D printing techniques. It reveals that the MLS‐printed metallic structures exhibit better performance, indicating that the MLS technology has great potential to print 3D metallic electromagnetic designs.

Abstract Background Rebound hyperglycemia following the resolution of diabetic ketoacidosis (DKA) is common in pediatric patients with type 1 diabetes, increasing the risk of recurrent DKA and complicating the transition to subcutaneous insulin. Multiple studies suggest that early administration of long‐acting insulin analogs during DKA management safely improves this transition. Objective This study aimed to determine whether early insulin glargine administration in children with DKA prevents rebound hyperglycemia and recurrent ketosis without increasing the rate of hypoglycemia or hypokalemia. Methods Patients aged 4 h of overlap with intravenous [IV] insulin) and Late (180 mg/dL) was lower in the Early group (66% vs. 85%, p ≤ 0.0001). Hypoglycemia (

Abstract Semiconductor nanocrystals (NCs) are promising materials for various applications. Two of four recently identified CuαZnβSnγSeδ (CZTSe) domains demonstrate metallic character, while the other two exhibit semiconductor character. The presence of both metallic and semiconductor domains in one NC can hugely benefit future applications. In contrast to traditional band gap studies in the NC community, this study emphasizes that NC domain interfaces also affect the electronic properties. Specifically, the measured band gap of a tetrapod‐shaped CZTSe NC is demonstrated to originate from two specific domains (tetragonal I4¯ and monoclinic P1c1 Cu2ZnSnSe4). The heterojunction between these two semiconductor domains exhibits a staggered type‐II band alignment, facilitating the separation of photogenerated electron‐hole pairs. Interestingly, tetrapod NCs have the potential to be efficient absorber materials with higher capacitance in photovoltaic applications due to the presence of both semiconductor/semiconductor interfaces and metal/semiconductor “Schottky”‐junctions. For the two photo‐absorbing domains, the calculated absorption spectra yield maximum photon‐absorption coefficients of about 105 cm−1 in the visible and UV regions and a theoretical solar power conversion efficiency up to 20.8%. These insights into the structure‐property relationships in CZTSe NCs will guide the design of more efficient advanced optical CZTSe materials for various applications.

Abstract Currently 1677 species are listed under the U.S. Endangered Species Act (ESA), yet only a small percentage have been delisted due to recovery. In the fall of 2021, the U.S. Fish and Wildlife Service proposed delisting 23 species due to extinction. Tracking changes in species ‘recovery status over time is critical to understanding species’ statuses, informing adaptive management strategies, and assessing the performance of the ESA to prevent further species loss. In this paper, we describe four key obstacles in tracking species recovery status under the ESA. First, ESA 5‐year reviews lack a standardized format and clear documentation. Second, despite having been listed for decades, many species still suffer major data gaps in their biology and threats, rendering it difficult if not impossible to track progress towards recovery. Third, many species have continued declining after listing, yet given the above (1 & 2), understanding potential causes (proximate and/or ultimate) can be difficult. Fourth, many species currently have no path to clear recovery, which represents a potential failing of the process. We conclude with a discussion of potential policy responses that could be addressed to enhance the efficacy of the ESA.

Abstract Dust dynamics influence planetary atmospheres. However, the settling velocity of dust—and thus its residence time in the atmosphere—is often mispredicted. Challenging, indirect experiments involving few ideal particles revealed that dust settling velocity deviates from Stokes' law under rarefied atmospheres. While useful, such experiments are inadequate to simulate more complex scenarios, including variable particles sizes and shapes. Here, we present direct measurements of settling velocity for spherical particles under Earth‐to‐Mars atmospheric pressures using time‐resolved particle image velocimetry (TR‐PIV), and validate their robustness with existing models. Our results demonstrate that TR‐PIV provides a relatively simple approach to quantifying dust settling velocity from direct observations of over 10,000 particles, enabling systematic investigations of dust settling under realistic scenarios. Such experiments will have significant implications for our understanding of Mars' past, present, and future ‐ from providing a tool to decipher its sedimentary record to enhancing predictive capabilities of atmospheric models.

Abstract Lead‐free metal halide perovskites can potentially be air‐ and water‐stable photocatalysts for organic synthesis, but there are limited studies on them for this application. Separately, machine learning (ML), a critical subfield of artificial intelligence, has played a pivotal role in identifying correlations and formulating predictions based on extensive datasets. Herein, an iterative workflow by incorporating high‐throughput experimental data with ML to discover new lead‐free metal halide perovskite photocatalysts for the aerobic oxidation of styrene is described. Through six rounds of ML optimization guided by SHapley Additive exPlanations (SHAP) analysis, BA2CsAg0.95Na0.05BiBr7 as a photocatalyst that afforded an 80% yield of benzoic acid under the standard conditions is identified, which is a 13‐fold improvement compared to the 6% with when using Cs2AgBiBr6 as the initial photocatalyst benchmark that is started. BA2CsAg0.95Na0.05BiBr7 can tolerate various functional groups with 22 styrene derivatives, highlighting the generality of the photocatalytic properties demonstrated. Radical scavenging studies and density functional theory calculations revealed that the formation of the reactive oxygen species superoxide and singlet oxygen in the presence of BA2CsAg0.95Na0.05BiBr7 are critical for photocatalysis.

Abstract Organic electrochemical transistors (OECTs) are of great interest in low‐power bioelectronics and neuromorphic computing, as they utilize organic mixed ionic‐electronic conductors (OMIECs) to transduce ionic signals into electrical signals. However, the poor environmental stability of OMIEC materials significantly restricts the practical application of OECTs. Therefore, the non‐fused planar naphthalenediimide (NDI)‐dialkoxybithiazole (2Tz) copolymers are fine‐tuned through varying ethylene glycol (EG) side chain lengths from tri(ethylene glycol) to hexa(ethylene glycol) (namely P‐XO, X = 3–6) to achieve OECTs with high‐stability and low threshold voltage. As a result, the NDI‐2Tz copolymers exhibit ambipolarity, rapid response (

Background Venous thromboembolism is associated with endothelial cell activation that contributes to the inflammation‐dependent activation of the coagulation system. Cellular damage is associated with the release of different species of extracellular RNA (eRNA) involved in inflammation and coagulation. TLR3 (toll‐like receptor 3), which recognizes (viral) single‐stranded or double‐stranded RNAs and self‐RNA fragments, might be the receptor of these species of eRNA during venous thromboembolism. Here, we investigate how the TLR3/eRNA axis contributes to venous thromboembolism. Methods and Results Thrombus formation and size in wild‐type and TLR3 deficient (−/−) mice were monitored by ultrasonography after venous thrombosis induction using the ferric chloride and stasis models. Mice were treated with RNase I, with polyinosinic‐polycytidylic acid, a TLR3 agonist, or with RNA extracted from murine endothelial cells. Gene expression and signaling pathway activation were analyzed in HEK293T cells overexpressing TLR3 in response to eRNA or in human umbilical vein endothelial cells transfected with a small interference RNA against TLR3. Plasma clot formation on treated human umbilical vein endothelial cells was analyzed. Thrombosis exacerbated eRNA release in vivo and increased eRNA content within the thrombus. RNase I treatment reduced thrombus size compared with vehicle‐treated mice (P

Abstract Molecular detection of environmental DNA (eDNA) and RNA (eRNA) allows highly sensitive qualitative (i.e., presence or absence) and quantitative (i.e., abundance) monitoring of aquatic bacteria. However, bacterial molecular diagnostics are limited by low positive predictive values. Protocols for bacterial eDNA and eRNA molecular monitoring have primarily focused on optimizing specimen collection, and the optimal method to purify bacterial nucleic material from postcollection aquatic specimens to maximize the analytical sensitivity of molecular diagnostics remains poorly defined. Accordingly, strategies to isolate bacterial eDNA and eRNA from fresh and saltwater were investigated. We evaluated two filtration and four nucleic acid purification systems as representative of current generation bacterial eDNA and eRNA isolation strategies for capacity to isolate bacterial eDNA and eRNA from prelysed (i.e., free‐nucleic acids) and viable (i.e., colony forming units, CFU) bacterial cells. We also compared the sensitivities of reverse transcription quantitative PCR (RT‐qPCR) and metagenomic shotgun microbiome sequencing. The optimal protocol used 0.7 μm borosilicate glass filters (Whatman plc) followed by extraction with the RNeasy PowerWater kit (Qiagen). The protocol had a very high analytical sensitivity (10−3–100 ng and 102–101 CFU detected in 500 mL) across multiple species of bacteria, when tested with either RTqPCR or metagenomic sequencing. Importantly, this study highlighted several limitations which are restrictive to both qualitative and quantitative bacterial eDNA and eRNA studies. First, a 12‐h time course between sampling and extraction revealed significant species‐specific changes in cell number and free‐nucleic acid concentrations can occur postspecimen collection. Second, we found Gram‐positive bacteria yielded less nucleic material compared to Gram‐negative bacteria suggesting bacterial eDNA and eRNA studies could be biased by microorganism genome stability and extraction efficiency. This study highlights the need to define the species‐specific diagnostic sensitivity of a protocol when monitoring aquatic bacterial eDNA and eRNA with molecular diagnostics.

Abstract DNA barcoding is commonly used for species identification. Despite this, there has not been a comprehensive assessment of the utility of DNA barcoding in crayfishes (Decapoda: Astacidea). Here we examined the extent to which local barcoding gaps (used for species identification) and global barcoding gaps (used for species discovery) exist among crayfishes, and whether global gaps met a previously suggested 10× threshold (mean interspecific difference being 10× larger than mean intra specific difference). We examined barcoding gaps using publicly available mitochondrial COI sequence data from the National Center for Biotechnology Information's nucleotide database. We created two versions of the COI datasets used for downstream analyses: one focused on the number of unique haplotypes (NH) per species, and another that focused on total number of sequences (NS; i.e., including redundant haplotypes) per species. A total of 81 species were included, with 58 species and five genera from the family Cambaridae and 23 species from three genera from the family Parastacidae. Local barcoding gaps were present in only 30 species (20 Cambaridae and 10 Parastacidae species). We detected global barcoding gaps in only four genera (Cambarus, Cherax, Euastacus, and Tenuibranchiurus), which were all below (4.2× to 5.2×) the previously suggested 10× threshold. We propose that a ~5× threshold would be a more appropriate working hypothesis for species discovery. While the NH and NS datasets yielded largely similar results, there were some discrepant inferences. To understand why some species lacked a local barcoding gap, we performed species delimitation analyses for each genus using the NH dataset. These results suggest that current taxonomy in crayfishes may be inadequate for the majority of examined species, and that even species with local barcoding gaps present may be in need of taxonomic revisions. Currently, the utility of DNA barcoding for species identification and discovery in crayfish is quite limited, and caution should be exercised when mitochondrial‐based approaches are used in place of taxonomic expertise. Assessment of the evidence for local and global barcoding gaps is important for understanding the reliability of molecular species identification and discovery, but outcomes are dependent on the current state of taxonomy. As this improves (e.g., via resolving species complexes, possibly elevating some subspecies to the species‐level status, and redressing specimen misidentifications in natural history and other collections), so too will the utility of DNA barcoding.

Abstract Impact craters that form on every planetary body provide a record of planetary surface evolution. On heavily cratered surfaces, new craters that form often overlap antecedent craters, but it is unknown how the presence of antecedent craters alters impact crater formation. We use overlapping complex crater pairs on the lunar surface to constrain this process and find that crater rims are systematically lower where they intersect antecedent crater basins. The rim morphology of the new crater depends on the depth of the antecedent crater and the degree of overlap between the craters. Our observations suggest that new craters do not always obliterate underlying topography and that transient rim collapse is altered by antecedent topography. This study represents the first formalization of the influence of antecedent topography on rim morphology and provides process insight into a common impact scenario relevant to the geology of potential Artemis landing sites.

Abstract Background Pathologic perivascular spaces (PVS), the fluid‐filled compartments surrounding brain vasculature, may underlie cognitive decline in Parkinson's disease (PD). However, whether this impacts specific cognitive domains has not been investigated. Objectives This study examined the relationship of PVS volume at baseline with domain‐specific and global cognitive change over 2 years in PD individuals. Methods A total of 39 individuals with PD underwent 3T T1w magnetic resonance imaging to determine PVS volume fraction (PVS volume normalized to total regional volume) within (i) centrum semiovale, (ii) prefrontal white matter (medial orbitofrontal, rostral middle frontal, and superior frontal), and (iii) basal ganglia. A neuropsychological battery included assessment of cognitive domains and global cognitive function at baseline and after 2 years. Results Higher basal ganglia PVS at baseline was associated with greater decline in attention, executive function, and global cognition scores. Conclusions While previous reports have associated elevated PVS volume in the basal ganglia with decline in global cognition in PD, our findings show such decline may affect the attention and executive function domains.

Abstract Aims To examine changes in advanced nurse practitioner (ANP) well‐being, satisfaction and motivation over a four‐year period. Design Longitudinal Cohort study. Methods Surveys were carried out each year from 2019 to 2022 with the same cohort of ANPs in the United Kingdom (UK). The survey consisted of demographics, questions on contemporary issues in advanced practice, National Health Service (NHS) staff survey questions and validated questionnaires. A core set of questions were asked every year with some changes in response to the COVID‐19 pandemic. Results Response rate ranged from 40% to 59% and appeared to be affected by COVID‐19. Staff satisfaction with pay and the well‐being score were stable throughout. Other questions on well‐being, job satisfaction and motivation saw statistically significant reductions after 4 years. Open‐ended questions about ongoing well‐being concerns show participants are concerned about exhaustion levels caused by workload, staffing issues, abuse from patients and colleagues' mental health. Conclusion The findings highlight a decline in ANP well‐being, job satisfaction and motivation post‐COVID‐19. Reasons for this, explored in the qualitative data, show that ANPs have faced extremely difficult working conditions. Urgent action is required to prevent a workforce retention crisis as many nursing staff are close to retirement and may not be motivated to remain in post. Impact This study has followed ANPs through the most challenging years the NHS has ever seen. Job satisfaction, motivation and enjoyment of the job all significantly reduced over time. In many areas, the ANP role has been used to fill medical workforce gaps, and this will become harder to do if ANPs are dissatisfied, disaffected and struggling with stress and burnout. Addressing these issues should be a priority for policymakers and managers. Patient or public contribution None as this study focussed on staff. Staff stakeholders involved in the design and conduct of the study.

Background Thoracic aortic aneurysm (TAA) is associated with significant morbidity and mortality. Although individuals with family histories of TAA often undergo clinical molecular genetic testing, adults with nonsyndromic TAA are not typically evaluated for genetic causes. We sought to understand the genetic contribution of both germline and somatic mosaic variants in a cohort of adult individuals with nonsyndromic TAA at a single center. Methods and Results One hundred eighty‐one consecutive patients 500×) targeted sequencing across 114 candidate genes associated with TAA and its related functional pathways. Samples from 354 age‐ and sex‐matched individuals without TAA were also sequenced, with a 2:1 matching. We found significant enrichments for germline (odds ratio [OR], 2.44, P=4.6×10−6 [95% CI, 1.67–3.58]) and also somatic mosaic variants (OR, 4.71, P=0.026 [95% CI, 1.20–18.43]) between individuals with and without TAA. Likely genetic causes were present in 24% with nonsyndromic TAA, of which 21% arose from germline variants and 3% from somatic mosaic alleles. The 3 most frequently mutated genes in our cohort were FLNA (encoding Filamin A), NOTCH3 (encoding Notch receptor 3), and FBN1 (encoding Fibrillin‐1). There was increased frequency of both missense and loss of function variants in TAA individuals. Conclusions Likely contributory dominant acting genetic variants were found in almost one quarter of nonsyndromic adults with TAA. Our findings suggest a more extensive genetic architecture to TAA than expected and that genetic testing may improve the care and clinical management of adults with nonsyndromic TAA.

Abstract The design of high‐entropy single‐atom catalysts (HESAC) with 5.2 times higher entropy compared to single‐atom catalysts (SAC) is proposed, by using four different metals (FeCoNiRu‐HESAC) for oxygen reduction reaction (ORR). Fe active sites with intermetallic distances of 6.1 Å exhibit a low ORR overpotential of 0.44 V, which originates from weakening the adsorption of OH intermediates. Based on density functional theory (DFT) findings, the FeCoNiRu‐HESAC with a nitrogen‐doped sample were synthesized. The atomic structures are confirmed with X‐ray photoelectron spectroscopy (XPS), X‐ray absorption (XAS), and scanning transmission electron microscopy (STEM). The predicted high catalytic activity is experimentally verified, finding that FeCoNiRu‐HESAC has overpotentials of 0.41 and 0.37 V with Tafel slopes of 101 and 210 mVdec−1 at the current density of 1 mA cm−2 and the kinetic current densities of 8.2 and 5.3 mA cm−2, respectively, in acidic and alkaline electrolytes. These results are comparable with Pt/C. The FeCoNiRu‐HESAC is used for Zinc–air battery applications with an open circuit potential of 1.39 V and power density of 0.16 W cm−2. Therefore, a strategy guided by DFT is provided for the rational design of HESAC which can be replaced with high‐cost Pt catalysts toward ORR and beyond.