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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 Objective Duchenne and Becker muscular dystrophies (DMD and BMD) are dystrophinopathies caused by variants in DMD gene, resulting in reduced or absent dystrophin. These conditions, characterized by muscle weakness, also manifest central nervous system (CNS) comorbidities due to dystrophin expression in the CNS. Prior studies have indicated a higher prevalence of epilepsy in individuals with dystrophinopathy compared to the general population. Our research aimed to investigate epilepsy prevalence in dystrophinopathies and characterize associated electroencephalograms (EEGs) and seizures. Methods We reviewed 416 individuals with dystrophinopathy, followed up at three centers between 2010 and 2023, to investigate the lifetime epilepsy prevalence and characterize EEGs and seizures in those individuals diagnosed with epilepsy. Associations between epilepsy and type of dystrophinopathy, genotype, and cognitive involvement were studied. Results Our study revealed a higher epilepsy prevalence than the general population (1.4%; 95% confidence interval: 0.7–3.2%), but notably lower than previously reported in smaller dystrophinopathy cohorts. No significant differences were found in epilepsy prevalence between DMD and BMD or based on underlying genotypes. Cognitive impairment was not found to be linked to higher epilepsy rates. The most prevalent epilepsy types in dystrophinopathies resembled those observed in the broader pediatric population, with most individuals effectively controlled through monotherapy. Interpretation The actual epilepsy prevalence in dystrophinopathies may be markedly lower than previously estimated, possibly half or even less. Our study provides valuable insights into the epilepsy landscape in individuals with dystrophinopathy, impacting medical care, especially for those with concurrent epilepsy.

Abstract Statins are used to reduce liver cholesterol levels but also carry a dose‐related risk of skeletal muscle toxicity. Concentrations of statins in plasma are often used to assess efficacy and safety, but because statins are substrates of membrane transporters that are present in diverse tissues, local differences in intracellular tissue concentrations cannot be ruled out. Thus, plasma concentration may not be an adequate indicator of efficacy and toxicity. To bridge this gap, we used physiologically based pharmacokinetic (PBPK) modeling to predict intracellular concentrations of statins. Quantitative data on transporter clearance were scaled from in vitro to in vivo conditions by integrating targeted proteomics and transporter kinetics data. The developed PBPK models, informed by proteomics, suggested that organic anion–transporting polypeptide 2B1 (OATP2B1) and multidrug resistance–associated protein 1 (MRP1) play a pivotal role in the distribution of statins in muscle. Using these PBPK models, we were able to predict the impact of alterations in transporter function due to genotype or drug–drug interactions on statin systemic concentrations and exposure in liver and muscle. These results underscore the potential of proteomics‐guided PBPK modeling to scale transporter clearance from in vitro data to real‐world implications. It is important to evaluate the role of drug transporters when predicting tissue exposure associated with on‐ and off‐target effects.

Objective Over 90 clinical trials demonstrate the efficacy of the collaborative care model (CoCM) to treat depression in primary care but there is significant variability in real‐world CoCM implementation and scalability. This study aimed to determine the feasibility and effectiveness of an adapted CoCM in a safety‐net primary care setting. Methods Bring It Up! (BIU) is a pilot trial comparing an adapted CoCM (intervention group) to usual care (historical controls) for primary care safety‐net clinic patients with depression. Inclusion criteria: (1) age ≥18; (2) Patient Health Questionnaire‐9 (PHQ‐9) score ≥10; and (3) major depressive disorder diagnosis. Patients who completed ≥6 months of treatment upon rolling enrollment (April 1, 2018–October 31, 2019) were included. Historical controls completed ≥6 months of usual care in 2017. BIU included all aspects of CoCM except accountable care and leveraged existing staff rather than a dedicated care manager. The primary outcome was depression remission (PHQ‐9

Store‐operated Ca2+ entry (SOCE) is a major mechanism for Ca2+ influx in colorectal cancer (CRC) cells. This mechanism, regulated by the filling state of the intracellular Ca2+ stores, is mediated by the endoplasmic reticulum Ca2+ sensors of the stromal interaction molecules (STIM) family [stromal interaction molecule 1 (STIM1) and STIM2] and the Ca2+‐release‐activated Ca2+ channels constituted by Orai family members, with predominance of calcium release‐activated calcium channel protein 1 (Orai1). CRC cells exhibit enhanced SOCE due to remodeling of the expression of the key SOCE molecular components. The enhanced SOCE supports a variety of cancer hallmarks. Here, we show that treatment of the colorectal adenocarcinoma cell lines HT‐29 and Caco‐2 with inanimate Lacticaseibacillus paracasei (CECT9610) and Lactiplantibacillus plantarum (CECT9608) attenuates SOCE, although no detectable effect is seen on SOCE in normal colon mucosa cells. The effect of Lacticaseibacillus paracasei and Lactiplantibacillus plantarum postbiotics was mediated by downregulation of Orai1 and STIM1, while the expression levels of Orai3 and STIM2 remained unaltered. Treatment of HT‐29 and Caco‐2 cells with inanimate Lacticaseibacillus paracasei and Lactiplantibacillus plantarum impairs in vitro migration by a mechanism likely involving attenuation of focal adhesion kinase (FAK) tyrosine phosphorylation. Cell treatment with the Orai1 inhibitor synta‐66 attenuates SOCE and prevents any further effect of Lacticaseibacillus paracasei and Lactiplantibacillus plantarum postbiotics. Together, our results indicate for the first time that Lacticaseibacillus paracasei and Lactiplantibacillus plantarum postbiotics selectively exert negative effects on Ca2+ influx through SOCE in colorectal adenocarcinoma cell lines, providing evidence for an attractive strategy against CRC.

Abstract Due to the environmental consequences of annual‐dominated cropping systems, there is an increasing need to identify agronomic strategies that incorporate perennial crops. One strategy for increasing perennial cover is through the targeted use of annually harvested perennial food and bioproduct crops in buffer strips, which has the potential to create new revenue streams for farmers and substantially mitigate agricultural nutrient pollution from conventional cropping systems. As buffers are typically installed on marginal land, it is critical to understand how landscape position influences the success of perennial crops. The objectives of this study were to determine the relatively early influence of landscape position on the productivity of a variety of perennial crops and their subsequent soil nutrients and soil water storing capabilities. In this experiment, nine perennial (alfalfa, alsike clover, indiangrass, switchgrass, big bluestem, prairie cordgrass, intermediate wheatgrass, high‐diversity polyculture, low‐diversity polyculture) and two annual (corn, soybean) crops were planted across two landscape positions (hillslope and deposition). Plant biomass, plant tissue nitrogen, soil moisture, and soil NO3‐N and NH4‐N were measured and compared at two different locations in Minnesota. Overall, the polyculture mixes, and to some extent intermediate wheatgrass, performed the best with respect to biomass production while also providing ecosystem services across most soil by landscape position combinations tested in this study. However, there were some important findings specific to each soil and landscape position combination, mainly oriented toward biomass production. We also observed temporal patterns in soil moisture and depth‐related patterns in soil N reductions. This study presents an opportunity to optimize the use of perennial crops on marginal agricultural lands for improved environmental and economic benefit.

Abstract A 3D metal‐only waveguide‐based phoenix cell for reflectarray is presented. The proposed cell consists of two concentric square waveguides and a metallic block in the centre, which offers two operation modes. The first mode uses its cross section to tune reflection phase while the second mode varies the heights of two waveguides to manipulate reflection phase. The principle of the two different modes is analysed in detail. A metal‐only reflectarray antenna at 20 GHz is designed based on the first mode of the phoenix cell. It is fabricated using selective laser melting 3D printing technology. A good agreement between simulations and measurements is achieved. The measured gain at 19.75 GHz is 30.25 dBi with an aperture efficiency of 51.17% respectively. Also, the measured 1‐dB gain bandwidth is 15% (19–22 GHz). A dual band metal‐only reflectarray operating at 20 and 25 GHz is designed based on the second mode of the phoenix cell. The two metal‐only reflectarray antennas fully demonstrate the capabilities of the proposed 3D metal‐only phoenix cell.

Oncolytic viruses (OVs) are biological therapeutic agents that selectively destroy cancer cells while sparing normal healthy cells. Besides direct oncolysis, OV infection induces a proinflammatory shift in the tumor microenvironment and the release of tumor‐associated antigens (TAAs) that might induce an anti‐tumor immunity. Due to their immunostimulatory effect, OVs have been explored for cancer vaccination against specific TAAs. However, this approach usually requires genetic modification of the virus and the production of a new viral vector for each target, which is difficult to implement for low prevalent antigens. In a recent study, Chiaro et al. presented an elegant proof of concept on how to implement the PeptiCRAd vaccination platform to overcome this limitation for the treatment of mesothelioma. Authors showed the feasibility of identifying immunogenic TAAs in human mesothelioma and using them to coat oncolytic adenovirus particles. The result was a customized virus‐based cancer vaccine that circumvents time and resource‐consuming steps incurred from genetically engineering viruses. Although some questions remain to be addressed, this interesting approach suggests novel strategies for personalized cancer medicine using oncolytic virotherapy.

Abstract Aims Heart failure (HF) is a chronic disease affecting 64 million people worldwide and places a severe burden on society because of its mortality, numerous re‐hospitalizations and associated costs. HeartLogic™ is an algorithm programmed into implanted devices incorporating several biometric parameters which aims to predict HF episodes. It provides an index which can be monitored remotely, allowing pre‐emptive treatment of congestion to prevent acute decompensation. We aim to assess the impact and security of pre‐emptive HF management, guided by the HeartLogic™ index. Methods and results The HeartLogic™ France Cohort Study is an investigator‐initiated, prospective, multi‐centre, non‐randomized study. Three hundred ten patients with a history of HF (left ventricular ejection fraction ≤40%; or at least one episode of clinical HF with elevated NT‐proBNP ≥450 ng/L) and implanted with a cardioverter defibrillator enabling HeartLogic™ index calculation will be included across 10 French centres. The HeartLogic™ index will be monitored remotely for 12 months and in the event of a HeartLogic™ index ≥16, the local investigator will contact the patient for assessment and adjust HF treatment as necessary. The primary endpoint is unscheduled hospitalization for HF. Secondary endpoints are all‐cause mortality, cardiovascular death, HF‐related death, unscheduled hospitalizations for ventricular or atrial arrhythmia and HeartLogic™ index evolution over time. Blood samples will be collected for biobanking, and quality of life will be assessed. Finally, the safety of a HeartLogic™‐triggered strategy for initiating or increasing diuretic therapy will be assessed. A blind and independent committee will adjudicate the events. Conclusions The HeartLogic™ France Cohort Study will provide robust real‐world data in a cohort of HF patients managed with the HeartLogic™ algorithm allowing pre‐emptive treatment of heart failure exacerbations.

Abstract Aims Frailty and dependence are frequent in patients admitted for acute heart failure (AHF), but their prognostic significance is unknown, especially in young adults. We aimed to study in adults admitted for AHF, regardless of age, the effect of frailty and dependence on the incidence of mortality and a combined event of mortality, readmissions for AHF, and visits to the emergency room (ER) for AHF at 1 and 6 months. Methods and results We designed a prospective cohort study by including all the patients with AHF admitted in our Cardiology Department from July 2020 through May 2021. A multidimensional geriatric assessment was performed during the admission. We clinically followed up the patients 6 months after discharge. We enrolled 202 patients. The mean age was 73 ± 12.32 years, and 100 (49.5%) of the patients were elderly (>75 years). Just 78 patients (38.6%) were women, and 100 (49.5%) had previous HF. Frailty (FRAIL ≥ 3) was observed in 68 (33.7%) patients (mean FRAIL score: 1.88 ± 1.48). Dependence (Barthel

Abstract In 2020, the novel severe acute respiratory syndrome coronavirus outbreak emerged as a public health emergency. Three years later, we are still assessing the effects caused by the coronavirus disease (COVID‐19) and by the lifestyle changes due to prevention measures, like social isolation. Here, we assessed the profile of both the anxiety screening scores and anthropometric variables in the university community, associated with the isolation due to the COVID‐19 pandemic. We analyzed social and epidemiological associated factors for anxiety and weight change to address and better identify the physical and mental conditions aggravated during the pandemic. This is a cross‐sectional study based on the 7‐item Generalized Anxiety Disorder Scale questionnaire applied virtually to university students and professors in the State of Rio de Janeiro (n = 480). In our population cohort, we showed that the majority of individuals showed moderate to severe anxiety and increased body weight during the COVID‐19 pandemic. The major demographic associated factors for higher anxiety levels were young age, female gender, and low family income. The main modifiable associated factors for both anxiety and weight gain were the negative changes in living habits. In addition, there was a trend toward severe anxiety and greater weight change in people with increased time in social isolation. In view of these results, we suggest that bad habits, adopted during the COVID‐19 pandemic, were the main reason for the high anxiety levels found in the studied population.

Abstract Background Systemic hypertension (SH) is a common cardiovascular disease in older cats that is treated primarily with the calcium channel blocker amlodipine besylate (AML). The systemic effect of AML on the classical and alterative arms of the renin‐angiotensin‐aldosterone system (RAAS) in cats is incompletely characterized. Hypothesis/Objectives To determine the effect of AML compared to placebo on circulating RAAS biomarkers in healthy cats using RAAS fingerprinting. Animals Twenty healthy client‐owned cats. Methods Cats were administered amlodipine besylate (0.625 mg in toto) or placebo by mouth once daily for 14 days in a crossover design with a 4‐week washout period. Plasma AML concentrations and RAAS biomarker concentrations were measured at multiple timepoints after the final dose in each treatment period. Time‐weighted averages for RAAS biomarkers over 24 hours after dosing were compared between treatment groups using Wilcoxon rank‐sum testing. Results Compared to placebo, AML treatment was associated with increases in markers of plasma renin concentration (median 44% increase; interquartile range [IQR] 19%‐86%; P = .009), angiotensin I (59% increase; IQR 27‐101%; P = .006), angiotensin II (56% increase; IQR 5‐70%; P = .023), angiotensin IV (42% increase; −19% to 89%; P = .013); and angiotensin 1‐7 (38% increase; IQR 9‐118%; P = .015). Conclusions and Clinical Importance In healthy cats, administration of AML resulted in nonspecific activation of both classical and alternative RAAS pathways.

Abstract Background No available literature supports the claim that the patellar and withdrawal (flexor) reflexes are the only reliable segmental reflexes in dogs. Objective Measure intra‐ and interobserver agreement of 8 segmental reflexes in dogs without clinical evidence of orthopedic or neurologic disease. Animals One‐hundred and one client‐ or staff‐owned dogs between 1 and 10 years of age with no clinical evidence of orthopedic disease, myelopathy, or neuromuscular disease. Methods Descriptive study. The intraobserver proportion of agreement (%) of responses to selected segmental reflexes in right versus left limbs by 3 observers was calculated and reported. The interobserver agreement of 2 observers of responses to selected reflexes was estimated by calculating proportions of agreement, kappa values, and 95% confidence intervals. A segmental reflex with an acceptable agreement was defined as that with a proportion of agreement ≥90% and a Kappa value ≥0.61 in both limbs. Results The intraobserver proportion of agreement for all 3 observers was high (≥95%) for the extensor carpi radialis, withdrawal, patellar, and cranial tibial reflexes. Between observers 1 and 3 and observers 2 and 3, the interobserver proportion of agreement was high (≥ 92%) for the extensor carpi radialis (κ 0.66, not determined [ND]), withdrawal (both limbs, κ ND), patellar (κ ND), and cranial tibial reflexes (κ ND). Conclusions and Clinical Importance The extensor carpi radialis, withdrawal, patellar, and cranial tibial reflexes had a higher proportion of agreement and kappa values between 2 observers.

Abstract Several investigational agents are under evaluation in systemic lupus erythematosus (SLE) clinical trials but quantitative frameworks to enable comparison of their efficacy to reference benchmark treatments are lacking. To benchmark SLE treatment effects and identify clinically important covariates, we developed a model‐based meta‐analysis (MBMA) within a latent variable model framework for efficacy end points and SLE composite end point scores (BILAG‐based Composite Lupus Assessment and Systemic Lupus Erythematosus Responder Index) using aggregate‐level data on approved and investigational therapeutics. SLE trials were searched using PubMed and www.clinicaltrials.gov for treatment name, SLE and clinical trial as search criteria that resulted in four data structures: (1) study and investigational agent, (2) dose and regimen, (3) baseline descriptors, and (4) outcomes. The final dataset consisted of 25 studies and 81 treatment arms evaluating 16 different agents. A previously developed (K Goteti et al. 2022) SLE latent variable model of data from placebo arms (placebo + standard of care treatments) was used to describe aggregate SLE end points over time for the various SLE placebo and treatment arms in a Bayesian MBMA framework. Continuous dose‐effect relationships using a maximum effect model were included for anifrolumab, belimumab, CC‐220 (iberdomide), epratuzumab, lulizumab pegol, and sifalimumab, whereas the remaining treatments were modeled as discrete dose effects. The final MBMA model was then used to benchmark these compounds with respect to the maximal efficacy on the latent variable compared to the placebo. This MBMA illustrates the application of latent variable models in understanding the trajectories of composite end points in chronic diseases and should enable model‐informed development of new investigational agents in SLE.

Abstract Time series of radiative cooling of the upper mesosphere and lower thermosphere (UMLT) by carbon dioxide (CO2) are examined for evidence of trends over 20 years. Radiative cooling rates in K day−1 provided by the SABER instrument are converted to time series of infrared power radiated from three distinct layers between 0.1 hPa and 0.0001 hPa (65–105 km). Linear regression against time and a predictor for solar variability provides estimates of the trend in exiting longwave radiation (ELR) from these layers. Trends in ELR are not significantly different from zero at 95% or 99% confidence in each layer. These results demonstrate energy conservation in the UMLT on decadal time scales and show that the UMLT continues to radiate the same amount of energy it receives despite cooling and contracting over two decades. These results are enabled by the long‐term stability of the SABER instrument calibration.

Abstract Extracellular vesicles (EVs) serve as pivotal mediators of intercellular communication in both health and disease, delivering biologically active molecules from vesicle‐producing cells to recipient cells. In the context of HIV infection, EVs have been shown to carry the viral protein Nef, a key pathogenic factor associated with HIV‐related co‐morbidities. Despite this recognition, the specific localisation of Nef within the vesicles has remained elusive. This study addresses this critical knowledge gap by investigating Nef‐containing EVs. Less than 1% of the total released Nef was associated with EVs; most Nef existed as free protein released by damaged cells. Nevertheless, activity of EV‐associated Nef in downregulating the major cholesterol transporter ABCA1, a critical aspect linked to the pathogenic effects of Nef, was comparable to that of free Nef present in the supernatant. Through a series of biochemical and microscopic assays, we demonstrate that the majority of EV‐associated Nef molecules are localised on the external surface of the vesicles. This distinctive distribution prompts the consideration of Nef‐containing EVs as potential targets for immunotherapeutic interventions aimed at preventing or treating HIV‐associated co‐morbidities. In conclusion, our results shed light on the localisation and functional activity of Nef within EVs, providing valuable insights for the development of targeted immunotherapies to mitigate the impact of HIV‐associated co‐morbidities.

ABSTRACT Objective The objective of this study was to associate the epidemiological and clinical characteristics of patients hospitalized for COVID‐19 with the progression to critical illness and death in northwestern Mexico. Methods From March to October 2020, we collected the demographic and clinical characteristics of 464 hospitalized patients from northwestern Mexico. Results Sixty‐four percent (295/464) of the patients became critically ill. Age, occupation, steroid and antibiotic use at previous hospitalization, and underlying diseases (hypertension, obesity, and chronic kidney disease) were associated with critical illness or death (p:

Abstract Introduction Health challenges in the 21st century underscore the need for adaptable and innovative approaches in public health. Academic institutions can and should contribute much more effectively to generate and translate scientific knowledge that will result in better programmes to improve societal health. Academic accountability to local communities and society requires universities to actively engage with local communities, understanding the context, their needs, and leveraging their knowledge and local experience. The Programme Science initiative provides a framework to optimize the scale, quality and impact of public health programmes, by integrating diverse approaches during the iterative cycle of research and practice within the strategic planning, programme implementation and programme management and evaluation. We illustrate how the Programme Science framework could be a useful tool for academic institutions to accomplish accountability to local communities and society through the experience of Project HOPE in Peru. Discussion Project HOPE applied the Programme Science framework to introduce HPV self‐sampling into a women's health programme in Peru. Collaboration with local authorities and community members was pivotal in all phases of the project, ensuring interventions aligned with community needs and addressing social determinants of health. The HOPE Ladies—community women trained and empowered to promote and provide the HPV kits—crafted the messages used through the study and developed strategies to reach individuals and provided support to women's journey through health centres. By engaging communities in co‐creating knowledge and addressing health inequities, academic institutions can generate contextually relevant and socially just scientific knowledge. The active participation of community women in Project HOPE was instrumental in improving service utilization and addressing barriers to self‐sampling. Conclusions The Programme Science approach offers a pathway for academic institutions to enhance their accountability to communities and society at large. By embedding researchers within public health programmes and prioritizing community engagement, academic institutions can ensure that research findings directly inform policy improvements and programmatic decisions. However, achieving this requires a realignment of research agendas and recognition of the value of community engagement. Establishing Programme Science networks involving academia, government and funding entities can further reinforce academic accountability and enhance the impact of public health programmes.

Abstract We aimed to describe how breastfeeding relates to adherence to complementary feeding (CF) recommendations, diet diversification and feeding skills development and whether sociodemographic factors explain any differences observed. The Scottish Maternal Infant and Nutrition Survey for infants aged 8–12 months collected breastfeeding history, CF practices, diet and sociodemographic data using a self‐completion questionnaire. Non‐healthful CF practices were starting CF

Abstract Root architectural traits play pivotal roles in plant adaptation to drought stress, and hence they are considered promising targets in breeding programs. Here, we phenotyped eight root architecture traits in response to well‐watered and drought stress conditions in 200 spring barley (Hordeum vulgare L.) inbred lines over two consecutive field seasons. Root architecture traits were less developed under drought in both seasons when compared with control treatments. Genetic variation in root architectural traits was dissected employing a genome‐wide association study (GWAS) coupled with linkage disequilibrium mapping. GWAS uncovered a total of 186 significant single nucleotide polymorphism‐trait associations for eight root traits under control, drought, and drought‐related indices. Of these, a few loci for root traits were detected on chromosomes 3 and 5, which co‐located with QTL identified in previous studies. Interestingly, 13 loci showed simultaneou associations with multiple root traits under drought and drought‐related indices. These loci harbored candidate genes, which included a wide range of drought‐responsive components such as transcription factors, binding proteins, protein kinases, nutrient and ion transporters, and stress signaling factors. For instance, two candidate genes, HORVU7Hr3G0713160 and HORVU6H r3G0626550, are orthologous to AtACX3 and AtVAMPs, which have reported functions in root length‐mediated drought tolerance and as a key protein in abiotic stress tolerance, respectively. Interestingly, one of these loci underlying a high‐confidence candidate gene NEW ENHANCER OF ROOT DWARFISM1 (NERD1) showed involvement with root development. An allelic variation of this locus in non‐coding region was significantly associated with increased root length under drought. Collectively, these results offer promising multi‐trait affecting loci and candidate genes underlying root phenotypic responses to drought stress, which may provide valuable resources for genetic improvement of drought tolerance in barley.

Abstract Maintaining genetic purity and true‐to‐type clone identification are important action steps in breeding programs. This study aimed to develop a universal set of kompetitive allele‐specific polymerase chain reaction (KASP)‐based single nucleotide polymorphism (SNP) markers for routine breeding activities. Ultra‐low‐density SNP markers were created using an initial set of 173,675 SNPs that were obtained from whole‐genome resequencing of 333 diverse white Guinea yam (Dioscorea rotundata Poir) genotypes. From whole‐genome resequencing data, 99 putative SNP markers were found and successfully converted to high‐throughput KASP genotyping assays. The markers set was validated on 374 genotypes representing six yam species. Out of the 99 markers, 50 were highly polymorphic across the species and could distinguish different yam species and pedigree origins. The selected SNP markers classified the validation population based on the different yam species and identified potential duplicates within yam species. Through penalized analysis, the male parent of progenies involved in polycrosses was successfully predicted and validated. Our research was a trailblazer in validating KASP‐based SNP assays for species identification, parental fingerprinting, and quality control (QC) and quality assurance (QA) in yam breeding programs.

Abstract Antimicrobial resistance (AMR) is an escalating global health crisis, driven by the overuse and misuse of antibiotics. Multidrug‐resistant Gram‐negative bacteria, such as Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae, are particularly concerning due to their high morbidity and mortality rates. In this context, endolysins, derived from bacteriophages, offer a promising alternative to traditional antibiotics. This study introduces LysJEP8, a novel endolysin derived from Escherichia phage JEP8, which exhibits remarkable antimicrobial activity against key Gram‐negative members of the ESKAPE group. Comparative assessments highlight LysJEP8's superior performance in reducing bacterial survival rates compared to previously described endolysins, with the most significant impact observed against P. aeruginosa, and notable effects on A. baumannii and K. pneumoniae. The study found that LysJEP8, as predicted by in silico analysis, worked best at lower pH values but lost its effectiveness at salt concentrations close to physiological levels. Importantly, LysJEP8 exhibited remarkable efficacy in the disruption of P. aeruginosa biofilms. This research underscores the potential of LysJEP8 as a valuable candidate for the development of innovative antibacterial agents, particularly against Gram‐negative pathogens, and highlights opportunities for further engineering and optimization to address AMR effectively.

Abstract Microalgae offer a sustainable source of omega − 3 fatty acids that can replace fish oil in aquafeeds, but the nutritional benefits are not always clear, particularly when microalgae are used as complete oil replacements in starter feeds. We compared the survival, growth, omega − 3 deposition and composition of the gut microbiota of juvenile mixed‐sex Nile tilapia (Oreochromis niloticus) that had been fed over a 3‐month period on six isonitrogenous, isolipidic and isocaloric aquafeeds that varied only on the contribution of fish oil, soya oil and microalgae (Schizochytrium) oil as lipid sources. Survival was not affected by diet, but fish fed a diet where the entire oil component (5%) was replaced by microalgae oil grew twice as fast as fish fed plant oil or a mixture of plant and fish oil. Dietary omega − 3 content was strongly correlated with omega − 3 deposition in the fish fillet. Complete replacement of fish oil by plant oil caused a significant decrease in the abundance of Peptostreptococcaceae and an increase in the abundance of Aeromonadaceae which is often associated with an inflammatory response in the fish gut. In contrast, when fish and soya oil in the reference diet were replaced by 100% microalgae oil, an increase in Mycobacteriaceae was observed. Our study indicates that Schizochytrium oil can be used to improve the growth of Nile tilapia and increase its omega − 3 content without any of the detrimental effects on the gut microbiome typically associated with some plant oil replacements.

Abstract Climate change is projected to worsen ozone pollution over many populated regions, with larger impacts at higher concentrations. More intense and frequent ozone episodes risk setbacks to human health and environmental policy achievements. However, assessing these changes is complicated by uncertain climate sensitivity, closely related to climate model response, and internal variability in simulations projecting climate's influence on air quality. Here, leveraging a global modeling framework that one‐way couples a human activity model, an Earth system model of intermediate complexity, and an atmospheric chemistry model, we investigate the role of climate sensitivity in climate‐induced changes to high ozone pollution episodes in the United States using multiple greenhouse gas emissions scenarios, representations of climate sensitivity, and initial condition members. We bias correct and evaluate historical model simulations, identifying modeled and observed O3 episodes using extreme value theory, and extend the approach to projections of mid‐ and end‐century climate impacts. Results show that the influence of climate sensitivity can be as significant as that of greenhouse gas emissions scenario absent precursor emissions changes. Climate change is projected to increase the magnitude of the highest annually occurring O3 concentrations by over 2.3 ppb on average across the U.S. at mid‐century under a high climate sensitivity and moderate emissions scenario, but the increase is limited to less than 0.3 ppb under lower climate sensitivity. Further, we show that areas in the U.S. currently meeting air quality standards risk being pushed into non‐compliance due to a climate‐induced increase in frequency of high ozone days.

Abstract Background Social isolation and loneliness can occur in all age groups, and they are linked to increased mortality and poorer health outcomes. There is a growing body of research indicating inconsistent findings on the effectiveness of interventions aiming to alleviate social isolation and loneliness. Hence the need to facilitate the discoverability of research on these interventions. Objectives To map available evidence on the effects of in‐person interventions aimed at mitigating social isolation and/or loneliness across all age groups and settings. Search Methods The following databases were searched from inception up to 17 February 2022 with no language restrictions: Ovid MEDLINE, Embase, EBM Reviews—Cochrane Central Register of Controlled Trials, APA PsycInfo via Ovid, CINAHL via EBSCO, EBSCO (all databases except CINAHL), Global Index Medicus, ProQuest (all databases), ProQuest ERIC, Web of Science, Korean Citation Index, Russian Science Citation Index, and SciELO Citation Index via Clarivate, and Elsevier Scopus. Selection Criteria Titles, abstracts, and full texts of potentially eligible articles identified were screened independently by two reviewers for inclusion following the outlined eligibility criteria. Data Collection and Analysis We developed and pilot tested a data extraction code set in Eppi‐Reviewer. Data was individually extracted and coded. We used the AMSTAR2 tool to assess the quality of reviews. However, the quality of the primary studies was not assessed. Main Results A total of 513 articles (421 primary studies and 92 systematic reviews) were included in this evidence and gap map which assessed the effectiveness of in‐person interventions to reduce social isolation and loneliness. Most (68%) of the reviews were classified as critically low quality, while less than 5% were classified as high or moderate quality. Most reviews looked at interpersonal delivery and community‐based delivery interventions, especially interventions for changing cognition led by a health professional and group activities, respectively. Loneliness, wellbeing, and depression/anxiety were the most assessed outcomes. Most research was conducted in high‐income countries, concentrated in the United States, United Kingdom, and Australia, with none from low‐income countries. Major gaps were identified in societal level and community‐based delivery interventions that address policies and community structures, respectively. Less than 5% of included reviews assessed process indicators or implementation outcomes. Similar patterns of evidence and gaps were found in primary studies. All age groups were represented but more reviews and primary studies focused on older adults (≥60 years, 63%) compared to young people (≤24 years, 34%). Two thirds described how at‐risk populations were identified and even fewer assessed differences in effect across equity factors for populations experiencing inequities. Authors’ Conclusions There is growing evidence that social isolation and loneliness are public health concerns. This evidence and gap map shows the available evidence, at the time of the search, on the effectiveness of in‐person interventions at reducing social isolation and loneliness across all ages and settings. Despite a large body of research, with much of it published in more recent years, it is unevenly distributed geographically and across types of interventions and outcomes. Most of the systematic reviews are of critically low quality, indicating the need for high quality reviews. This map can guide funders and researchers to consider the areas in which the evidence is lacking and to address these gaps as future research priorities.

Abstract Objectives This is the protocol for a Campbell systematic review. The objectives are as follows: The aim of this systematic review is to examine the scientific evidence available from low‐ and middle‐income countries on the association of breakfast consumption habits and anthropometry/adiposity‐ and nutrition‐related outcomes in adolescents aged 10–19 years old.

Abstract The learning health system (LHS) model was proposed to provide real‐time, bi‐directional flow of learning using data captured in health information technology systems to deliver rapid learning in healthcare delivery. As highlighted by the landmark National Academy of Medicine report “Crossing the Quality Chasm,” the U.S. healthcare delivery industry represents complex adaptive systems, and there is an urgent need to develop innovative methods to identify efficient team structures by harnessing real‐world care delivery data found in the electronic health record (EHR). We offer a discussion surrounding the complexities of team communication and how solutions may be guided by theories such as the Multiteam System (MTS) framework and the Multitheoretical Multilevel Framework of Communication Networks. To advance healthcare delivery science and promote LHSs, our team has been building a new line of research using EHR data to study MTS in the complex real world of cancer care delivery. We are developing new network metrics to study MTSs and will be analyzing the impact of EHR communication network structures on patient outcomes. As this research leads to patient care delivery interventions/tools, healthcare leaders and healthcare professionals can effectively use health IT data to implement the most evidence‐based collaboration approaches in order to achieve the optimal LHS and patient outcomes.

Abstract A strategic roadmap for noncarbonized fuels is a global priority, and the reduction of carbon dioxide emissions is a key focus of the Paris Agreement to mitigate the effects of rising temperatures. In this context, hydrogen is a promising noncarbonized fuel, but the pace of its implementation will depend on the engineering advancements made at each step of its value chain. To accelerate its adoption, various applications of hydrogen across industries, transport, power, and building sectors have been identified, where it can be used as a feedstock, fuel, or energy carrier and storage. However, widespread usage of hydrogen will depend on its political, industrial, and social acceptance. It is essential to carefully assess the hydrogen value chain and compare it with existing solar technologies. The major challenge to widespread adoption of hydrogen is its cost as outlined in the roadmap for hydrogen. It needs to be produced at the levelized cost of hydrogen of less than $2 kg−1 to be competitive with the established process of steam methane reforming. Therefore, this review provides a comprehensive analysis of each step of the hydrogen value chain, outlining both the current challenges and recent advances.

Abstract The silicon vacancy (SiV) center in diamond is drawing much attention due to its optical and spin properties, attractive for quantum information processing and sensing. Comparatively little is known, however, about the dynamics governing SiV charge state interconversion mainly due to challenges associated with generating, stabilizing, and characterizing all possible charge states, particularly at room temperature. Here, multi‐color confocal microscopy and density functional theory are used to examine photo‐induced SiV recombination — from neutral, to single‐, to double‐negatively charged — over a broad spectral window in chemical‐vapor‐deposition (CVD) diamond under ambient conditions. For the SiV0 to SiV‐ transition, a linear growth of the photo‐recombination rate with laser power at all observed wavelengths is found, a hallmark of single photon dynamics. Laser excitation of SiV‒, on the other hand, yields only fractional recombination into SiV2‒, a finding that is interpreted in terms of a photo‐activated electron tunneling process from proximal nitrogen atoms.

Background Hemoglobin (Hgb) drop without bleeding is common among patients undergoing transcatheter aortic valve replacement; however, the clinical implications of significant Hgb drop have not been fully evaluated. Methods and Results Consecutive patients undergoing transcatheter aortic valve replacement at our institution from 2011 to 2021 were retrospectively reviewed. Three groups were assessed: no Hgb drop and no bleed (NoD‐NoB [reference group]), Hgb drop with bleed, and Hgb drop and no bleed (D‐NoB). Hgb drop was defined as ≥3 g/dL decrease from pre‐ to post‐transcatheter aortic valve replacement. Outcomes of interest were in‐hospital death and 1‐year all‐cause mortality. A total of 1851 cases with complete Hgb data were included: NoD‐NoB: n=1579 (85.3%); D‐NoB: n=49 (2.6%); Hgb drop with bleed: n=223 (12.6%). Compared with NoD‐NoB, the D‐NoB group was older (81.1 versus 78.9 years of age) with higher preprocedure Hgb (12.9 versus 11.7 g/dL). In‐hospital death rate was higher among patients with D‐NoB versus NoD‐NoB (4.5% versus 0.8%, P

Abstract Numerous policy and international frameworks consider that “destructive fishing” hampers efforts to reach sustainability goals. Though ubiquitous, “destructive fishing” is undefined and therefore currently immeasurable. Here we propose a definition developed through expert consultation: “Destructive fishing is any fishing practice that causes irrecoverable habitat degradation, or which causes significant adverse environmental impacts, results in long‐term declines in target or nontarget species beyond biologically safe limits and has negative livelihood impacts.” We show strong stakeholder support for a definition, consensus on many biological and ecological dimensions, and no clustering of respondents from different sectors. Our consensus definition is a significant step toward defining sustainable fisheries goals and will help interpret and implement global political commitments which utilize the term “destructive fishing.” Our definition and results will help reinforce the Food and Agricultural Organization's Code of Conduct and meaningfully support member countries to prohibit destructive fishing practices.

Abstract The increased availability of remote sensing products and new legislative agendas are driving a growing focus on farm‐level traceability and monitoring to tackle commodity‐driven deforestation. Here, we use data on land use change in Brazil (1985–2021) from Mapbiomas to demonstrate how analyses of the drivers of deforestation are sensitive to the scale of analysis: while pixel‐ or property‐level analyses identify proximate drivers of deforestation, analyses at larger scales (subnational regions or countries) capture more complex land use dynamics, including indirect land use change. We argue that initiatives which seek to monitor and address commodity‐driven deforestation—such as the European Union's deforestation due‐diligence regulation and the World Business Council on Sustainable Development's Greenhouse Gas Protocol—must be conscient of these wider land use dynamics. Only by measuring progress and defining success at multiple scales can initiatives for sustainable commodity sourcing create the right mix of incentives for addressing deforestation.

Abstract Over 60% of relapsed/refractory (R/R) large B‐cell lymphoma (LBCL) patients who receive chimeric antigen receptor (CAR) T cells will experience disease progression. There is no standard next line of therapy and information in this setting is scarce and heterogeneous. We analyzed 387 R/R LBCL patients who progressed after CAR T cells from July 2018 until March 2022 in Spain and the United Kingdom. Median overall survival (OS) was 5.3 months, with significant differences according to the interval between infusion and progression (6 months [not reached]). After progression, 237 (61%) patients received treatment. Focusing on the first subsequent therapy, overall (complete) response rates were 67% (38%) for polatuzumab–bendamustine–rituximab (POLA), 51% (36%) for bispecific antibodies (BsAb), 45% (35%) for radiotherapy (RT), 33% (26%) for immune checkpoint inhibitors (ICIs), 25% (0%) for lenalidomide (LENA), and 25% (14%) for chemotherapy (CT). In terms of survival, 12‐month progression‐free survival and OS was 36.2% and 51.0% for POLA, 32.0% and 50.1% for BsAb, 30.8% and 37.5% for RT, 29.9% and 27.8% for ICI, 7.3% and 20.8% for LENA, and 6.1% and 18.3% for CT. Thirty‐two (14%) patients received an allogeneic hematopoietic cell transplant with median OS not reached after a median follow‐up of 15.1 months. In conclusion, patients with R/R LBCL who progress within the first 2 months after CAR T‐cell therapy have dismal outcomes. Novel targeted agents, such as polatuzumab and BsAbs, can achieve prolonged survival after CAR T‐cell therapy failure.

Abstract Permeability transition pore (PTP) opening dissipates ion and electron gradients across the internal mitochondrial membrane (IMM), including excess Ca2+ in the mitochondrial matrix. After opening, immediate PTP closure must follow to prevent outer membrane disruption, loss of cytochrome c, and eventual apoptosis. Flickering, defined as the rapid alternative opening/closing of PTP, has been reported in heart, which undergoes frequent, large variations in Ca2+. In contrast, in tissues that undergo depolarization events less often, such as the liver, PTP would not need to be as dynamic and thus these tissues would not be as resistant to stress. To evaluate this idea, it was decided to follow the reversibility of the permeability transition (PT) in isolated murine mitochondria from two different tissues: the very dynamic heart, and the liver, which suffers depolarizations less frequently. It was observed that in heart mitochondria PT remained reversible for longer periods and at higher Ca2+ loads than in liver mitochondria. In all cases, Ca2+ uptake was inhibited by ruthenium red and PT was delayed by Cyclosporine A. Characterization of this phenomenon included measuring the rate of oxygen consumption, organelle swelling and Ca2+ uptake and retention. Results strongly suggest that there are tissue‐specific differences in PTP physiology, as it resists many more Ca2+ additions before opening in a highly active organ such as the heart than in an organ that seldom suffers Ca2+ loading, such as the liver.

Executive summary Microbes are all pervasive in their distribution and influence on the functioning and well‐being of humans, life in general and the planet. Microbially‐based technologies contribute hugely to the supply of important goods and services we depend upon, such as the provision of food, medicines and clean water. They also offer mechanisms and strategies to mitigate and solve a wide range of problems and crises facing humanity at all levels, including those encapsulated in the sustainable development goals (SDGs) formulated by the United Nations. For example, microbial technologies can contribute in multiple ways to decarbonisation and hence confronting global warming, provide sanitation and clean water to the billions of people lacking them, improve soil fertility and hence food production and develop vaccines and other medicines to reduce and in some cases eliminate deadly infections. They are the foundation of biotechnology, an increasingly important and growing business sector and source of employment, and the centre of the bioeconomy, Green Deal, etc. But, because microbes are largely invisible, they are not familiar to most people, so opportunities they offer to effectively prevent and solve problems are often missed by decision‐makers, with the negative consequences this entrains. To correct this lack of vital knowledge, the International Microbiology Literacy Initiative–the IMiLI–is recruiting from the global microbiology community and making freely available, teaching resources for a curriculum in societally relevant microbiology that can be used at all levels of learning. Its goal is the development of a society that is literate in relevant microbiology and, as a consequence, able to take full advantage of the potential of microbes and minimise the consequences of their negative activities. In addition to teaching about microbes, almost every lesson discusses the influence they have on sustainability and the SDGs and their ability to solve pressing problems of societal inequalities. The curriculum thus teaches about sustainability, societal needs and global citizenship. The lessons also reveal the impacts microbes and their activities have on our daily lives at the personal, family, community, national and global levels and their relevance for decisions at all levels. And, because effective, evidence‐based decisions require not only relevant information but also critical and systems thinking, the resources also teach about these key generic aspects of deliberation. The IMiLI teaching resources are learner‐centric, not academic microbiology‐centric and deal with the microbiology of everyday issues. These span topics as diverse as owning and caring for a companion animal, the vast range of everyday foods that are produced via microbial processes, impressive geological formations created by microbes, childhood illnesses and how they are managed and how to reduce waste and pollution. They also leverage the exceptional excitement of exploration and discovery that typifies much progress in microbiology to capture the interest, inspire and motivate educators and learners alike. The IMiLI is establishing Regional Centres to translate the teaching resources into regional languages and adapt them to regional cultures, and to promote their use and assist educators employing them. Two of these are now operational. The Regional Centres constitute the interface between resource creators and educators–learners. As such, they will collect and analyse feedback from the end‐users and transmit this to the resource creators so that teaching materials can be improved and refined, and new resources added in response to demand: educators and learners will thereby be directly involved in evolution of the teaching resources. The interactions between educators–learners and resource creators mediated by the Regional Centres will establish dynamic and synergistic relationships–a global societally relevant microbiology education ecosystem–in which creators also become learners, teaching resources are optimised and all players/stakeholders are empowered and their motivation increased. The IMiLI concept thus embraces the principle of teaching societally relevant microbiology embedded in the wider context of societal, biosphere and planetary needs, inequalities, the range of crises that confront us and the need for improved decisioning, which should ultimately lead to better citizenship and a humanity that is more sustainable and resilient. Abstract The biosphere of planet Earth is a microbial world: a vast reactor of countless microbially driven chemical transformations and energy transfers that push and pull many planetary geochemical processes, including the cycling of the elements of life, mitigate or amplify climate change (e.g., Nature Reviews Microbiology, 2019, 17, 569) and impact the well‐being and activities of all organisms, including humans. Microbes are both our ancestors and creators of the planetary chemistry that allowed us to evolve (e.g., Life's engines: How microbes made earth habitable, 2023). To understand how the biosphere functions, how humans can influence its development and live more sustainably with the other organisms sharing it, we need to understand the microbes. In a recent editorial (Environmental Microbiology, 2019, 21, 1513), we advocated for improved microbiology literacy in society. Our concept of microbiology literacy is not based on knowledge of the academic subject of microbiology, with its multitude of component topics, plus the growing number of additional topics from other disciplines that become vitally important elements of current microbiology. Rather it is focused on microbial activities that impact us–individuals/communities/nations/the human world–and the biosphere and that are key to reaching informed decisions on a multitude of issues that regularly confront us, ranging from personal issues to crises of global importance. In other words, it is knowledge and understanding essential for adulthood and the transition to it, knowledge and understanding that must be acquired early in life in school. The 2019 Editorial marked the launch of the International Microbiology Literacy Initiative, the IMiLI. Here, we present our concept of how microbiology literacy may be achieved and the rationale underpinning it; the type of teaching resources being created to realise the concept and the framing of microbial activities treated in these resources in the context of sustainability, societal needs and responsibilities and decision‐making; and the key role of Regional Centres that will translate the teaching resources into local languages, adapt them according to local cultural needs, interface with regional educators and develop and serve as hubs of microbiology literacy education networks. The topics featuring in teaching resources are learner‐centric and have been selected for their inherent relevance, interest and ability to excite and engage. Importantly, the resources coherently integrate and emphasise the overarching issues of sustainability, stewardship and critical thinking and the pervasive interdependencies of processes. More broadly, the concept emphasises how the multifarious applications of microbial activities can be leveraged to promote human/animal, plant, environmental and planetary health, improve social equity, alleviate humanitarian deficits and causes of conflicts among peoples and increase understanding between peoples (Microbial Biotechnology, 2023, 16(6), 1091–1111). Importantly, although the primary target of the freely available (CC BY‐NC 4.0) IMiLI teaching resources is schoolchildren and their educators, they and the teaching philosophy are intended for all ages, abilities and cultural spectra of learners worldwide: in university education, lifelong learning, curiosity‐driven, web‐based knowledge acquisition and public outreach. The IMiLI teaching resources aim to promote development of a global microbiology education ecosystem that democratises microbiology knowledge.

Abstract Elucidating how cell populations promote onset and progression of intervertebral disc degeneration (IDD) has the potential to enable more precise therapeutic targeting of cells and mechanisms. Single‐cell RNA‐sequencing (scRNA‐seq) is performed on surgically separated annulus fibrosus (AF) (19,978; 26,983 cells) and nucleus pulposus (NP) (20,884; 24,489 cells) from healthy and diseased human intervertebral discs (IVD). In both tissue types, depletion of cell subsets involved in maintenance of healthy IVD is observed, specifically the immature cell subsets – fibroblast progenitors and stem cells – indicative of an impairment of normal tissue self‐renewal. Tissue‐specific changes are also identified. In NP, several fibrotic populations are increased in degenerated IVD, indicating tissue‐remodeling. In degenerated AF, a novel disease‐associated subset is identified, which expresses disease‐promoting genes. It is associated with pathogenic biological processes and the main gene regulatory networks include thrombospondin signaling and FOXO1 transcription factor. In NP and AF cells thrombospondin protein promoted expression of genes associated with TGFβ/fibrosis signaling, angiogenesis, and nervous system development. The data reveal new insights of both shared and tissue‐specific changes in specific cell populations in AF and NP during IVD degeneration. These identified mechanisms and molecules are novel and more precise targets for IDD prevention and treatment.

Background The optimal strategy for transferring patients to specialized acute stroke care remains controversial. This substudy of the Effect of Direct Transportation to Thrombectomy‐Capable Center vs Local Stroke Center on Neurological Outcomes in Patients with suspected Large‐Vessel Occlusion Stroke in Nonurban Areas (RACECAT) trial aims to investigate the impact of local hospital characteristics and performance on the optimal transport strategy and stroke outcomes. Methods This was a secondary post hoc analysis of the RACECAT trial, evaluating factors potentially associated with functional outcomes among patients initially evaluated at a local stroke center (Local‐SC) versus a thrombectomy‐capable center. The primary outcome was the shift in the 90‐day modified Rankin Scale score in the target population of the RACECAT trial. Door‐to‐needle time, level of care of the Local‐SC (telestroke versus primary stroke center), the specialty of the physician involved with therapeutic decisions, and Local‐SC case volume were assessed for subgroup analyses. Results Of the 1367 patients included in the analysis, 903 had acute ischemic strokes (modified intention to treat). The 90‐day modified Rankin Scale score was associated with door‐to‐needle time in the entire modified intention‐to‐treat cohort (P = 0.026) and in patients initially evaluated in a Local‐SC (P = 0.063), and with local hospital level of care (telestroke versus primary stroke center; P = 0.10). There was a trend favoring direct transport to thrombectomy‐capable center for patients whose assigned Local‐SC was a telestroke center (adjusted odds ratio [OR], 1.47 [95% CI, 0.93–2.33] versus 0.94 [95% CI, 0.71–1.24]; Pinteraction = 0.08) or had door‐to‐needle time over the global median (adjusted OR, 1.52 [95% CI, 0.97–2.40] versus 0.94 [95% CI, 0.71–1.25]; Pinteraction = 0.06). In patients with confirmed large‐vessel occlusion, the benefit of direct transport to thrombectomy‐capable centers when the Local‐SC was a telestroke center (Pinteraction = 0.04) or had longer door‐to‐needle time (Pinteraction = 0.07) was more evident. Conclusions Direct transport to thrombectomy‐capable centers may be preferable in areas primarily covered by telestroke or Local‐SCs with poorer performance, especially in patients with large‐vessel occlusion. These findings can contribute to refining prehospital triage strategies and optimizing stroke systems of care.

Background Cardiogenic shock (CS) is a significant complication of Takotsubo syndrome (TTS), contributing to heightened mortality and morbidity. Despite this, the Society for Cardiovascular Angiography and Interventions (SCAI) staging system for CS severity lacks validation in patients with TTS and CS. This study aimed to characterize a patient cohort with TTS using the SCAI staging system and assess its utility in cases of TTS complicated by CS. Methods and Results From a TTS national registry, 1591 consecutive patients were initially enrolled and stratified into 5 SCAI stages (A through E). Primary outcome was all‐cause in‐hospital mortality; secondary end points were TTS‐related in‐hospital complications and 1‐year all‐cause mortality. After exclusions, the final cohort comprised 1163 patients, mean age 71.0±11.8 years, and 87% were female. Patients were categorized across SCAI shock stages as follows: A 72.1%, B 12.2%, C 11.2%, D 2.7%, and E 1.8%. Significant variations in baseline demographics, comorbidities, clinical presentations, and in‐hospital courses were observed across SCAI shock stages. After multivariable adjustment, each higher SCAI shock stage showed a significant association with increased in‐hospital mortality (adjusted odds ratio: 1.77–29.31) compared with SCAI shock stage A. Higher SCAI shock stages were also associated with increased 1‐year mortality. Conclusions In a large multicenter patient cohort with TTS, the functional SCAI shock stage classification effectively stratified mortality risk, revealing a continuum of escalating shock severity with higher stages correlating with increased in‐hospital mortality. This study highlights the applicability and prognostic value of the SCAI staging system in TTS‐related CS.

Abstract Coregistration is among the most important and challenging tasks when dealing with multiple synthetic aperture radar (SAR) images, especially when they are acquired at different time instants and characterised by low signal to noise power ratio (SNR) that contributes to their coherence reduction. However, even if some technological expedients could be implemented to maintain the same trajectory and to compensate for these inaccuracies during the acquisition campaign, multitemporal SAR images always need additional registration refinements after compression. Usually, to coregister a series of multitemporal SAR images, one of them is selected as the master, and the remainders are separately registered to it. Differently, in this study, a new strategy is developed to jointly coregister a stack of multitemporal SAR images. It is based on the exploitation of the cross‐correlations in turn computed from each couple of cross‐correlations (a.k.a. cross‐cross‐correlations) of the extracted patches. By doing so, the method is capable of exploiting also the respective misregistration information between the slaves during the estimation process. In this respect, this methodology is applied to enhance the registration capabilities of the constrained Least Squares (CLS) optimisation method, which instead does not account for the reciprocal information related to the slaves. Several tests are performed on multitemporal airborne‐measured SAR data. Obtained results show the effectiveness of the proposed algorithm in terms of achieved root mean square error for images affected by respective rotations also in comparison with the CLS counterpart.

Abstract The efficient, reliable, and resilient supply of electricity has become essential for social and economic well‐being of the modern society. However, more frequent occurrence of extreme weather events has exposed inequity in the planning and operation practices of power distribution systems, evidenced in higher vulnerability and longer power interruptions for some parts of the grid as compared to others. This paper proposes an equity‐aware power distribution system restoration model in an effort to ensure a more equitable yet resilient power distribution operation after outages. To this end, the proposed equity‐aware distribution system restoration model balances the efficiency of the restoration operation and the equitable allocation of distributed energy resources among affected customers after an outage, while prioritizing the critical infrastructure (e.g. hospitals). The results demonstrate the effectiveness of the proposed framework to ensure a more equitable restoration process as measured by the proposed fairness and restoration performance indices.

Abstract Pearl oil apricot almonds are rich in proteins, being a valuable raw material for preparing antioxidant peptides. In this study, almond protein hydrolysates (APHs) were obtained by enzymatic hydrolysis and divided into APHs‐1 (10 kDa). APHs‐1‐c, purified from APHs‐1, was proved to show the strongest antioxidant effect through activity tracking experiments. APHs‐1‐c also can protect HepG2 cells against oxidative damage by reducing intracellular reactive oxygen species and MDA levels, elevating glutathione levels as well as increasing superoxide dismutase and catalase activities, and its protective effect is related to the Keap1–Nrf2 signaling pathway. Forty bioactive peptide sequences were identified from APHs‐1‐c, and Thr‐Glu‐Asp‐Asp‐Trp‐Arg‐Trp‐His (TEDDWRWH; P1), Trp‐Tyr‐Asp‐Asn‐Glu‐Trp‐Gly‐Tyr‐Arg (WYDNEWGYR; P2), and Ala‐Glu‐Asp‐His‐Glu‐Trp‐Trp‐Arg (AEDHEWWWR; P3) had the most potential for antioxidant activity by molecular docking studies. P1, P2, and P3 showed desirable 1,1‐diphenyl‐2‐picrylhydrazyl radical scavenging activity (IC50 = 0.634–3.381 mmol/L), 2,2′‐azino‐bis (3‐ethylbenzothiazoline‐6‐sulfonic acid) diammonium salt radical scavenging activity (IC50 = 0.221–0.309 mmol/L), and ferric‐reducing antioxidant power. These results suggested that almonds protein hydrolysates and its derived antioxidant peptides could serve as potential ingredients applied in functional foods.

Abstract Background Atopic dermatitis is a chronic inflammatory skin disease and inflammation has been implicated in development of other chronic diseases, but few studies have examined the relationship with dementia. Objectives This study examines associations of atopic dermatitis (AD) and systemic inflammation in adolescence measured using erythrocyte sedimentation rate (ESR), as well as AD diagnosed in adulthood, with dementia risk. Methods We used three Swedish register‐based cohorts. Cohort I (N = 795,680) comprised men, born in 1951–1968, who participated in the military conscription examinations with physician‐assessed AD and ESR; Cohort II (N = 1,757,600) included men and women, born in 1951–1968; and Cohort III (N = 3,988,783) included all individuals in Sweden, born in 1930–1968. We used Cox regression, estimating hazard ratios (HR), with the follow‐up from 50 years of age to dementia diagnosis, date of emigration, death, or 31 December 2018, whichever occurred first. Further, we used a sibling comparison design to adjust for unmeasured confounders shared among siblings. Results Cohort I: 1466 dementia events were accrued during follow‐up of 7.8 years, with a crude rate of 21.6 [95% confidence interval (CI): 20.6, 22.8] per 100,000 person‐years. Cohort II: 3549 dementia events were accrued during follow‐up of 7.4 years, with a crude rate of 23.7 (95% CI: 22.9, 24.5) per 100,000 person‐years. Cohort III: 120,303 dementia events were accrued during follow‐up of 23.7 years, with a crude rate of 180.3 (95% CI: 179.3, 181.3) per 100,000 person‐years. In multivariable analysis using Cohort I, there was no association between AD and dementia [HR 0.68 (95% CI 0.32, 1.43)], nor with moderate [HR 0.71 (95% CI: 0.46, 1.10)] or high [HR 1.23 (95% CI: 0.87, 1.75)] ESR. AD was not associated with dementia risk in Cohort II [HR 1.28 (0.97, 1.71)] or Cohort III [HR 1.01 (0.92, 1.11)]. Conclusions AD was not associated with dementia risk, neither was systemic inflammation measured by ESR in adolescence.

Abstract Background An especially significant event in the patient–oncologist relationship is the initial consultation, where many complex topics—diagnosis, treatment intent, and often, prognosis—are discussed in a relatively short period of time. This study aimed to measure patients' understanding of the information discussed during their first medical oncology visit and their satisfaction with the communication from medical oncologists. Methods Between January and August 2021, patients without prior systemic treatment of their gastrointestinal malignancy (GI) attending the Princess Margaret Cancer Centre (PMCC) were approached within 24 h of their initial consultation to complete a paper‐based questionnaire assessing understanding of their disease (diagnosis, treatment plan/intent, and prognosis) and satisfaction with the consultation. Medical oncology physicians simultaneously completed a similar questionnaire about the information discussed at the initial visit. Matched patient–physician responses were compared to assess the degree of concordance. Results A total of 184 matched patient–physician surveys were completed. The concordance rates for understanding of diagnosis, treatment plan, treatment intent, and prognosis were 92.9%, 59.2%, 66.8%, and 59.8%, respectively. After adjusting for patient and physician variables, patients who reported treatment intent to be unclear at the time of the consultation were independently associated with lower satisfaction scores (global p = 0.014). There was no statistically significant association between patient satisfaction and whether prognosis was disclosed (p = 0.08). Conclusion An in‐depth conversation as to what treatment intent and prognosis means is reasonable during the initial medical oncology consultation to ensure patients and caregivers have a better understanding about their cancer.

Abstract Background Small non‐coding (snc)RNAs, including microRNAs and P‐element induced wimpy testis (PIWI)‐interacting‐RNAs (piRNAs), crucially regulate gene expression in both physiological and pathological conditions. In particular, some muscle‐specific microRNAs (myomiRs) have been involved in the pathogenesis of cancer‐induced muscle wasting. The aims of the present study were (i) to profile sncRNAs in both skeletal muscle and plasma of gastrointestinal cancer patients and (ii) to investigate the association among differentially expressed sncRNAs and the level of muscularity at body composition analysis. Methods Surgical patients with gastrointestinal cancer or benign disease were recruited. Blood samples and muscle biopsies (rectus abdominis) were collected during surgery. Low muscularity patients were those at the lowest tertile of skeletal muscle index (SMI; CT‐scan), whereas moderate/high muscularity patients were in the middle and highest SMI tertiles. SncRNAs in the muscle were assessed by RNAseq, circulating microRNAs were evaluated by qPCR. Results Cancer patients (n = 25; 13 females, 52%) showed a mean age of 71.6 ± 11.2 years, a median body weight loss of 4.2% and a mean BMI of 27.0 ± 3.2 kg/m2. Control group (n = 15; 9 females, 60%) showed a mean age 58.1 ± 13.9 years and a mean BMI of 28.0 ± 4.3 kg/m2. In cancer patients, the median L3‐SMI (cm2/m2) was 42.52 (34.42; 49.07). Males showed a median L3‐SMI of 46.08 (41.17–51.79) and females a median L3‐SMI of 40.77 (33.73–42.87). Moderate‐high and low muscularity groups included 17 and 8 patients, respectively. As for circulating microRNAs, miR‐21‐5p and miR‐133a‐3p were up‐regulated in patients compared with controls, whereas miR‐15b‐5p resulted down‐regulated in the same comparison (about 30% of control values). Sample clustering by muscularity and sex revealed increased miR‐133a‐3p and miR‐206 only in moderate‐high muscularity males. SncRNA profiling in the muscle identified 373 microRNAs and 190 piRNAs (72.5% and 18.7% of raw reads, respectively). As for microRNAs, 10 were up‐regulated, and 56 were down‐regulated in cancer patients versus controls. Among the 24 dysregulated piRNAs, the majority were down‐regulated, including the top two most expressed piRNAs in the muscle (piR‐12790 and piR‐2106). Network analysis on validated mRNA targets of down‐regulated microRNAs revealed miR‐15b‐5p, miR‐106a‐5p and miR‐106b‐5p as main interactors of genes related to ubiquitin ligase/transferase activities. Conclusions These results show dysregulation of both muscle microRNAs and piRNAs in cancer patients compared with controls, the former following a sex‐specific pattern. Changes in circulating microRNAs are associated with the degree of muscularity rather than body weight loss.

Abstract Objectives Determine factors associated with delayed endoscopic sinus surgery (ESS) in patients with chronic rhinosinusitis (CRS). Methods This is a retrospective cohort study conducted at a tertiary care academic center. Patients were included in the study if they were at least 18 years old and underwent surgery for CRS. Electronic medical records were retrospectively reviewed to collect demographic and clinical data. Patients with CRS secondary to another pathology such as malignancy were excluded. Multiple linear regression was performed to determine factors associated with the number of days between a patient's preoperative consultation and the date of surgery. Results A total of 103 patients with a mean age of 46.6 ± 16.8 years were included in the analysis; 51.5% of patients were females, 46.6% identified as White, and 29.1% identified as Hispanic. The majority of patients (67.0%) had preferred provider organization health insurance; 43.7% of patients had nasal polyps, 70.9% had a deviated nasal septum, and the mean preoperative Sinonasal Outcomes Test‐22 (SNOT‐22) score was 41.0 ± 23.8. The mean time to surgery after the final preoperative visit was 71.7 days ± 65.6 days. Hispanic ethnicity was associated with increased time to surgery (p

Abstract Acute gastroenteritis is one of the most common diseases in children and an important cause of morbidity and mortality worldwide. No specific treatment is available; therefore, management is exclusively symptomatic. Xyloglucan has been approved in Europe as a class IIa medical device for restoration of the physiological functions of the intestinal wall. Our objective was to assess efficacy and safety of xyloglucan for the treatment of acute gastroenteritis in children. We performed a triple‐blind, randomized placebo‐controlled clinical trial in four primary care centers and one continued care hospital center. The study population comprised children with acute gastroenteritis aged >3 months and

Abstract Cashew nut is a globally popular nut not only for its delicious and crunchy flavor but also for bioactive compounds, which present positive benefits to human health. Different parts of cashew have characteristic compounds. The kernel of cashew nut is rich in fatty acids, the testa is rich in polyphenols, cashew apple is rich in polyphenols and carotenoids, and phenols with aliphatic long chain are present in the cashew nutshell liquid. Therefore, the edible part of cashew possesses a wide range of bioactive compounds, with reported biological properties, including anti‐tumor, brain health, cardiovascular and cerebrovascular protection, anti‐diabetic, gastroprotection, pathophysiological disorders protection, and antioxidant. On the other hand, the inedible part of cashew, the cashew nutshell liquid, could play an important role in the industry as surface coatings, insulating formulations and so on. Hence, there are considerable demands to increase the added value of cashew, thereby exploring greater economic value. Thus, this review summarizes nutrients, bioactive compounds, biological functions, and applications of Anacardium occidentale to provide a theoretical basis and inspiration for further in‐depth studies and utilization.