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Abstract Young children receiving outpatient cancer care are vulnerable to undermanaged pain. App‐based solutions that provide pain treatment advice to parents in real‐time and in all environments may improve access to quality pain care. We used a parent co‐design approach involving iterative rounds of user testing and software modification to develop a usable Pain Caregiver Resource (PainCaRe) real‐time pediatric cancer pain management app. Parents of children (2–11 years) with cancer completed three standardized modules using a PainCaRe prototype. App usability and acceptability were evaluated using the validated System Usability Scale and a thematic analysis of app testing sessions and interviews. Iterative testing sessions were conducted until data saturation. Interview themes were synthesized into action items that guided revisions to PainCaRe and additional testing rounds were conducted as necessary. Twenty‐two parents participated in three testing cycles. Overall, parents described PainCaRe as an acceptable and potentially clinically useful pain management tool. Mean system usability scores were in the acceptable scale range during each testing cycle. Usability issues identified and resolved included those related to software malfunction, complicated app navigation logic, lack of clarity on pain assessment questions, and the need for pain management advice specifically tailored to child developmental stage. Using co‐design methods, the PainCaRe cancer pain management app was successfully refined for its acceptability and utility to parents. Next steps will include a PainCaRe pilot study before evaluating the impact of the app on younger children's pain outcomes in a randomized controlled trial.

Abstract PACIFIC‐PGx evaluated the feasibility of implementing pharmacogenetics (PGx) screening in Australia and the impact of DPYD/UGT1A1 genotype‐guided dosing on severe fluoropyrimidine (FP) and irinotecan‐related toxicities and hospitalizations, compared to historical controls. This prospective single arm trial enrolled patients starting FP/irinotecan for any cancer between 7 January 2021 and 25 February 2022 from four Australian hospitals (one metropolitan, three regional). During the accrual period, 462/487 (95%) consecutive patients screened for eligibility for DPYD and 50/109 (46%) for UGT1A1 were enrolled and genotyped (feasibility analysis), with 276/462 (60%) for DPYD and 30/50 (60%) for UGT1A1 received FP/irinotecan (safety analysis). DPYD genotyping identified 96% (n = 443/462) Wild‐Type, 4% (n = 19/462) Intermediate Metabolizers (50% dose reduction), and 0% Poor Metabolizers. UGT1A1 genotyping identified 52% (n = 26/50) Wild‐Type, 40% (n = 20/50) heterozygous, and 8% (n = 4/50) homozygous (30% dose reduction). Key demographics for the FP/irinotecan safety cohorts included: age range 23–89/34–74 years, male 56%/73%, Caucasian 83%/73%, lower gastrointestinal cancer 50%/57%. Genotype results were reported prior to cycle‐1 (96%), average 5–7 days from sample collection. PGx‐dosing for DPYD variant allele carriers reduced high‐grade toxicities compared to historic controls (7% vs. 39%; OR = 0.11, 95% CI 0.01–0.97, p = 0.024). High‐grade toxicities among Wild‐Type were similar (14% vs. 14%; OR = 0.99, 95% CI 0.64–1.54, p = 0.490). PGx‐dosing reduced FP‐related hospitalizations (−22%) and deaths (−3.7%) compared to controls. There were no high‐grade toxicities or hospitalizations for UGT1A1*28 homozygotes. PGx screening and prescribing were feasible in routine oncology care and improved patient outcomes. Findings may inform expanded PGx programs within cancer and other disease settings.

Abstract The EFSA Panel on Food Additives and Flavourings (FAF Panel) evaluated the safety of the extension of uses of quillaia extract (E 999) as a food additive in food supplements supplied in a solid or liquid form, excluding food supplements for infants and young children. Quillaia extract (E 999) was re‐evaluated in 2019 by the EFSA FAF Panel, which derived an acceptable daily intake (ADI) of 3 mg saponins/kg bw per day for E 999, while in 2024 a follow‐up of the re‐evaluation was published by the FAF Panel, recommending some modifications of the existing EU specifications for quillaia extract (E 999). Currently, quillaia extract (E 999) is authorised in two food categories (FCs) i.e. FC 4.1.4 ‘Flavoured drinks’ and FC 14.2.3 ‘Cider and perry’ (excluding cidre bouché, cydr jakościowy, perry jakościowe, cydr lodowy, perry lodowe). A ‘food supplements consumers only’ scenario was calculated for this opinion considering the proposed extension of uses, together with the current authorised uses at both the maximum permitted level (MPLs) and the typical reported use levels of quillaia extract (E 999) at the time of the 2019 re‐evaluation. The Panel concluded that the exposure estimates using the typical reported use levels for the currently authorised food categories and considering the proposed extension of uses for E 999 in FC 17.1 ‘Food supplements supplied in a solid form, excluding food supplement for infants and young children’ and FC 17.2 ‘Food supplements supplied in a liquid form, excluding food supplement for infants and young children’, if authorised, would not result in an exceedance of the ADI in any population group.

Abstract The EFSA Panel on Food Additive and Flavourings (FAF Panel) evaluated the safety of proposed changes to the currently permitted uses of the food additive steviol glycosides (E 960a–d) and of a proposed modification of the current acceptable daily intake (ADI) from 4 mg/kg body weight (bw) per day to 6 or 16 mg/kg bw per day, expressed as steviol equivalents. Currently, steviol glycosides (E 960a–d) are authorised in the EU in 32 different food categories (FCs). An extension of use was proposed for four new uses within FC 7.2 ‘Fine bakery wares’. In addition, an increase of the maximum permitted levels (MPLs) for FC 14.1.3 ‘Fruit nectars’ and for three uses within FC 14.1.4 ‘Flavoured drinks’ was requested. Consequently, the Panel updated the exposure estimates using the protocol for assessing exposure to sweeteners, developed to consider the specificities related to consumers' exposure to this functional class of food additives. Considering the proposed extension of use and increase of the MPLs, together with the currently authorised uses (at the MPLs) of E 960a–d, the highest 95th percentiles of exposure are 4.1 and 6.9 mg/kg bw per day for infants and toddlers, respectively. Based on the currently available absorption, distribution, metabolism and excretion (ADME) dataset for steviol glycosides (E 960a–d), the Panel concluded that that there is insufficient justification to increase the current ADI of 4 mg/kg bw per day, expressed as steviol equivalents. With respect to the proposed extension of use and increase of the MPLs, the Panel concluded that the calculated, conservative, dietary exposure would result in an increased exceedance of the ADI for toddlers at the 95th percentile.

ABSTRACT Coloniality is strongly shaped by aspects of social foraging behaviour. For example, colonies may be important sources of information, while food competition may increase foraging efforts and limit colony size. Understanding foraging ecology considering these apparent trade‐offs is required to develop a better understanding of colonial living. We combined animal‐borne GPS, cameras and dive recorders to study social foraging in breeding adult northern gannets Morus bassanus—a wide‐ranging colonial seabird. We first tested for indirect evidence of prey depletion around the colony by estimating dive location, depth and duration. Next, we tested for sociality during different behaviours (commuting, foraging and resting) and distance from the colony. Finally, we quantified flocks of inbound and outbound birds to compare social foraging between outbound and inbound legs of the commute. Dive probability and depth (n = 46 individuals; n = 1590 dives) increased with distance from the colony, creating dive clusters at ~100 and 180 km consistent with conspecific prey depletion. Camera stills (n = 8 individuals; n = 7495 images) show gannets are highly social, but this varied among behaviours. Sociality was highest during foraging and commuting; especially inbound and social foraging was more likely far from the colony. Gannets were equally likely to be solitary or social when leaving the colony but returning birds were more likely in larger flocks. In summary, despite experiencing intraspecific competition for food, gannets engage in dynamic, context‐dependent social foraging associations. Conspecifics aggregated far from the colony possibly because of a prey depletion halo closer to home, but this provided potential benefits via local enhancement and by returning to the colony in flocks. Our results therefore illustrate how competition may, paradoxically, facilitate some aspects of group foraging in colonial animals.

Abstract Objective This study investigates ChatGPT's accuracy, readability, understandability, and actionability in responding to patient queries on sudden sensorineural hearing loss (SSNHL) in English and Spanish, when compared to Google responses. The objective is to address concerns regarding its proficiency in addressing medical inquiries when presented in a language divergent from its primary programming. Study Design Observational. Setting Virtual environment. Methods Using ChatGPT 3.5 and Google, questions from the AAO‐HNSF guidelines were presented in English and Spanish. Responses were graded by 2 otolaryngologists proficient in both languages using a 4‐point Likert scale and the PEMAT‐P tool. To ensure uniform application of the Likert scale, a third independent evaluator reviewed the consistency in grading. Readability was evaluated using 3 different tools specific to each language. IBM SPSS Version 29 was used for statistical analysis using one‐way analysis of variance. Results Across both languages, the responses displayed a native‐level language proficiency. Accuracy was comparable between sources and languages. Google's Spanish responses had better readability (effect size 0.35, P

Abstract Background Chronic diseases are a considerable burden to health systems, communities, and patients. Much of this burden, however, could be prevented if interventions effective in reducing chronic disease risks were routinely implemented. Aims The aim of this paper is to discuss the role of public health agencies in preventing chronic disease through the application of learning health system (LHS) approaches to improve the implementation of evidence‐based interventions. Materials and Methods We draw on the literature and our experience operating a local LHS in Australia that has achieved rapid improvements in the implementation of chronic disease prevention interventions. Results The proposed LHS framework has been adapted to be both implementation and chronic disease prevention focused. The framework describes both broad improvement processes, and the infrastructure and other support (pillars) recommended to support its core functions. Conclusion The framework serves as a basis for further exploration of the potentially transformative role LHS's may have in addressing the chronic disease health crisis.

Abstract The present opinion is the follow‐up of the conclusions and recommendations of the Scientific Opinion on the re‐evaluation of silicon dioxide (E 551) as a food additive relevant to the safety assessment for all age groups. In addition, the risk assessment of silicon dioxide (E 551) for its use in food for infants below 16 weeks of age is performed. Based on the newly available information on the characterisation of the SAS used as E 551 and following the principles of the 2021 EFSA Guidance on Particle‐TR, the conventional safety assessment has been complemented with nano‐specific considerations. Given the uncertainties resulting from the limitations of the database and in the absence of genotoxicity concern, the Panel considered that it is not appropriate to derive an acceptable daily intake (ADI) but applied the margin of exposure (MOE) approach for the risk assessment. The Panel concluded that the MOE should be at least 36 for not raising a safety concern. The calculated MOEs considering the dietary exposure estimates for all population groups using the refined non‐brand loyal scenario, estimated at the time of the 2018 re‐evaluation, were all above 36. The Panel concluded that E 551 does not raise a safety concern in all population groups at the reported uses and use levels. The use of E 551 in food for infants below 16 weeks of age in FC 13.1.1 and FC 13.1.5.1 does not raise a safety concern at the current exposure levels. The Panel also concluded that the technical data provided support an amendment of the specifications for E 551 laid down in Commission Regulation (EU) No 231/2012. The paucity of toxicological studies with proper dispersion protocol (with the exception of the genotoxicity studies) creates uncertainty in the present assessment of the potential toxicological effects related to the exposure to E 551 nanosize aggregates.

Abstract The Panel on Food Additives and Flavourings (FAF) provides a scientific opinion re‐evaluating the safety of the two food additives argon (E 938) and helium (E 939). Argon (Ar) and helium (He) are two noble gases, highly stable single atoms. Their chemical inertness is well known. Their physicochemical properties have served as a basis for their previous evaluations by SCF and JECFA, which have considered the use of these food additives safe even in the absence of a toxicological evaluation. No business operator or other interested party provided information in response to the call for data published by EFSA to support the re‐evaluation of these two food additives with respect to their identity and specifications, manufacturing process (including the identification and quantification of potential impurities) and how they are applied to food to exert their technological function. One business operator replied to the call for data issued by EFSA reporting use levels of E 938 as a packaging gas in one food category. Based on their physicochemical properties, both gases are considered by the Panel to be of low toxicological concern when used as food additives. No information was available on the potential presence of impurities of toxicological concern resulting from the manufacturing process(es) applied to the production of the food additives E 938 and E 939. The Panel however noted that a minimum purity of 99.0% is required to comply with existing specifications. The Panel concluded that the use of argon (E 938) and helium (E 939) as food additives does not raise a safety concern. The Panel recommended an amendment of the existing EU specifications to introduce the respective CAS numbers.

Abstract Introduction People living with HIV have high rates of hypertension. Integrated HIV and hypertension care with aligned multi‐month dispensing of medications (MMD) could decrease the burden of care for individuals and health systems. We sought to describe hypertension control and evaluate its association with different durations of MMD among Malawian adults receiving integrated care with aligned dispensing of antiretroviral therapy (ART) and antihypertensive medication. Methods We conducted a cross‐sectional survey and retrospective chart review of adults (≥18 years) receiving integrated HIV and hypertension care on medications for both conditions for at least 1 year, with aligned MMD at seven clinics in Malawi. Data were collected from July 2021 to April 2022 and included socio‐demographics, clinical characteristics, antihypertensive medications and up to the three most recent blood pressure measurements. Bivariate analyses were used to characterize associations with hypertension control. Uncontrolled hypertension was defined as ≥2 measurements ≥140 and/or ≥90 mmHg. Chart reviews were conducted for a random subset of participants with uncontrolled hypertension to describe antihypertensive medication adjustments in the prior year. Results We surveyed 459 adults receiving integrated care with aligned dispensing (58% female; median age 54 years). Individuals most commonly received a 3‐month aligned dispensing of ART and antihypertensive medications (63%), followed by every 6 months (16%) and every 4 months (15%). Hypertension control was assessed in 359 respondents, of whom only 23% had controlled hypertension; 90% of individuals in this group reported high adherence to blood pressure medications (0−1 missed days/week). Control was more common among those with longer aligned medication dispensing intervals (20% among those with 1‐ to 3‐month dispensing vs. 28% with 4‐month dispensing vs. 40% with 6‐month dispensing, p = 0.011). Chart reviews were conducted for 147 individuals with uncontrolled hypertension. Most had high self‐reported adherence to blood pressure medications (89% missing 0−1 days/week); however, only 10% had their antihypertensive medication regimen changed in the prior year. Conclusions Uncontrolled hypertension was common among Malawian adults receiving integrated care with aligned MMD and was associated with shorter refill intervals and few antihypertensive medication escalations. Integrated care with aligned MMD is promising, but further work is needed to understand how to optimize hypertension outcomes.

Abstract The EFSA Panel on Food Additives and Flavourings (FAF) provides a scientific opinion on the safety of curdlan as a new food additive used as firming and gelling agent, stabiliser, thickener. Curdlan is a high molecular weight polysaccharide consisting of β‐1,3‐linked glucose units, produced by fermentation from Rhizobium radiobacter biovar 1 strain NTK‐u. The toxicological dataset consisted of sub‐chronic, chronic and carcinogenicity, reproductive and developmental toxicity studies as well as genotoxicity. In vivo data showed that curdlan is not absorbed as such but is extensively metabolised by the gut microbiota into CO2 and other innocuous compounds. Curdlan was not genotoxic and was well‐tolerated with no overt organ‐specific toxicity. Effects observed at very high doses of curdlan, such as decreased growth and increased cecum weight, are common for indigestible bulking compounds and therefore considered physiological responses. In a combined three‐generation reproductive and developmental toxicity study, decreased pup weight was observed during lactation at 7500 mg curdlan/kg body weight (bw) per day, the highest dose tested. The Panel considered the observed effects as treatment‐related and adverse, although likely secondary to nutritional imbalance and identified a conservative no observed adverse effect level (NOAEL) of 2500 mg/kg bw per day. Despite the limitations noted in the dataset, the Panel was able to conclude applying the margin of exposure (MOE) approach. Given that curdlan and its break‐down products are not absorbed and that the identified adverse effect is neither systemic nor local, no adjustment factor was deemed necessary. Thus, an MOE of at least 1 was considered sufficient. The highest exposure estimate was 1441 mg/kg bw per day in toddlers at the 95th percentile of the proposed maximum use level exposure assessment scenario. The Panel concluded that there is no safety concern for the use of curdlan as a food additive at the proposed uses and use levels.

Abstract Global food production relying on irrigated agriculture accounts for >70% of the global freshwater withdrawal. A thorough understanding of soil–water characteristics (SWCs) and critical soil–water values in the soil and subsoil is important for effective management of irrigated water. A critical soil–water “window” for plants is generally taken as the plant‐available water window without considering diffusion‐dominated soil aeration as a co‐requisite. This study examined SWC curves in vadose soil profiles (up to 1.5‐m depth) in eight pasture soils. The soil moisture measurements were made over matric potentials ranging from −1 to −1500 kPa using tension table and pressure plate apparatus. The van Genuchten model was used to parameterize the measured SWC curve, while the Millington‐Quirk model was used to derive soil–gas diffusivity from measured soil physical properties. We defined critical soil–water windows considering the threshold values for both plant‐available water and soil–gas diffusivity to ensure water and aeration corequisites for plant growth. The results clearly distinguished depth‐dependent regimes of gravitational, plant‐available, and unavailable water in selected profiles and their responses to soil structural changes across the depth. In some of the observed soil profiles, only 30%–60% of the plant‐available water window was able to be utilized by plants because the remainder existed under soil conditions where soil aeration was inadequate for plant growth, emphasizing the importance of considering both the plant's water and aeration requirements during irrigation scheduling. Further, the infiltration profiles in two selected soils under simulated irrigation highlighted the importance of a priori knowledge of the soil structure in deeper soil layers for scheduling irrigation.

Abstract Lions (Panthera leo) are declining across their range, mainly due to human‐induced habitat fragmentation and prey depletion. However, the South African lion population continues to grow. Unlike other range states, South Africa actively manages wild lions across a continuum of landscapes and ecological constraints. Many of these lions are in small, fenced reserves where managers seek to mimic ecological processes in small landscapes. However, the effectiveness of this management approach has not been evaluated against meta‐population criteria. Given that meta‐population dynamics allows species living in fragmented habitats to persist, we evaluated how South Africa's lion population complies with meta‐population criteria using national audit data between 2010 and 2019 from 49 fenced, wild lion reserves. The small, fenced reserves holding wild lions fulfil the criteria for meta‐population functionality. However, this functionality was achieved through haphazard and uncoordinated management actions and not through a coordinated approach. Our main recommendation is to consider implementing a more coordinated meta‐population management approach. At the very least, meta‐population management guidelines should be reviewed and updated on a regular basis, regular audits should be conducted and periodic genetic evaluation of the meta‐population (every 10 years) should be instituted. We recommend incentivising lion managers to enhance the conservation of lions in South Africa within a meta‐population framework. We also recommend a focus on improving decision making and policy procedures that facilitates compliance with relevant legislation aimed at achieving high levels of lion conservation‐governance efficiency. South Africa's meta‐population approach to wild lion management in small, fenced reserves is effective at conserving lions and contributing to lion conservation more broadly. In an increasingly fragmented landscape, the need for human management actions to ensure persistence of large carnivores is likely to increase. A managed meta‐population approach of fenced (or unfenced, but geographically isolated) populations is a useful tool for conservationists to consider worldwide.

Abstract Purpose The purpose of this study was to compare the biomechanical properties of a latest generation all‐suture anchor repair device (ASARD) for meniscal repair with that of a latest generation PEEK‐cage anchor repair device (PCARD) in an experimental setting using cadaveric menisci. Methods Twenty‐six menisci were obtained from the knees of fresh body donors. Artificially created meniscal lesions were treated randomly, using a single stitch with either an ASARD or a PCARD. Cyclic biomechanical testing, utilising a universal material testing machine and following an established protocol, was carried out and load‐to‐failure (LTF), displacement, stiffness, and mode‐of‐failure (MOF) reported. Results Mean LTF was found to be 61% higher in the ASARD group at 107.10 N (standard deviation [SD], 42.34), compared to 65.86 N (SD, 27.42) in the PCARD group with statistical significance (p = 0.022). The ASARD exhibited a trend towards higher stiffness (10.35 N; SD, 3.92 versus 7.78 N; SD; 3.59) and higher displacement at cycles one, 100, and 499 (1.64, 3.27, and 4.17 mm versus 0.93, 2.19, and 2.83 mm) compared to the PCARD. Cheese wiring was the most common mode‐of‐failure in both groups (76.9%). Conclusions This study demonstrates that an ASARD shows a higher mean LTF than a PCARD when compared in an experimental biomechanical setting. Level of evidence Level III

Abstract Background Currently recommended cancer screening programs address only part of the overall population cancer burden. Even populations deemed high‐risk for certain individual cancers experience a considerable potential burden of other cancers. However, few published cancer screening trials report the incidence of untargeted cancers. Methods The National Lung Screening Trial (NLST), initiated in 2002–2004, was a randomized controlled trial of lung cancer screening in adults with ≥30 pack‐years of smoking. Active follow‐up for incident invasive cancers continued through 2009. Results Among 53,229 NLST subjects (median follow‐up 6.5 years after randomization), the incidence of lung cancer was 615 per 100,000 person‐years (32% of 6142 overall first primary incident invasive cancers), and that of non‐lung cancer was 1327 per 100,000 (68%). Non‐lung cancer incidence exceeded that for lung cancer in all 5‐year age categories and all quintiles of smoking pack‐years. Besides lung cancer, the most common cancers were prostate, breast, colon/rectum, bladder, and head/neck; 23% were smoking‐related cancers, and 54% were cancer types lacking recommended population‐based screening modalities (32% excluding prostate). Non‐lung cancer comprised 48% of 1793 cancer deaths. Conclusions In the NLST, only 32% of first primary cancer incidence after study entry was lung, compared with 68% non‐lung. Even in a population at high risk for lung cancer, a single‐cancer screening test misses most cancers. Thus, in combination with existing single‐cancer screening modalities, multi‐cancer screening tests—which address many of the incident non‐lung cancers in this trial—have potential to address a currently inaccessible portion of cancer morbidity and mortality.

Abstract Regular measurement of realized genetic gain allows plant breeders to assess and review the effectiveness of their strategies, allocate resources efficiently, and make informed decisions throughout the breeding process. Realized genetic gain estimation requires separating genetic trends from nongenetic trends using the linear mixed model (LMM) on historical multi‐environment trial data. The LMM, accounting for the year effect, experimental designs, and heterogeneous residual variances, estimates best linear unbiased estimators of genotypes and regresses them on their years of origin. An illustrative example of estimating realized genetic gain was provided by analyzing historical data on fresh cassava (Manihot esculenta Crantz) yield in West Africa (https://github.com/Biometrics‐IITA/Estimating‐Realized‐Genetic‐Gain). This approach can serve as a model applicable to other crops and regions. Modernization of breeding programs is necessary to maximize the rate of genetic gain. This can be achieved by adopting genomics to enable faster breeding, accurate selection, and improved traits through genomic selection and gene editing. Tracking operational costs, establishing robust, digitalized data management and analytics systems, and developing effective varietal selection processes based on customer insights are also crucial for success. Capacity building and collaboration of breeding programs and institutions also play a significant role in accelerating genetic gains.

Abstract This study explored the acceptability of a novel pharmacist‐led pharmacogenetics (PGx) screening program among patients with cancer and healthcare professionals (HCPs) taking part in a multicenter clinical trial of PGx testing (PACIFIC‐PGx ANZCTR:12621000251820). Medical oncologists, oncology pharmacists, and patients with cancer from across four sites (metropolitan/regional), took part in an observational, cross‐sectional survey. Participants were recruited from the multicenter trial. Two study‐specific surveys were developed to inform implementation strategies for scaled and sustainable translation into routine clinical care: one consisting of 21 questions targeting HCPs and one consisting of 17 questions targeting patients. Responses were collected from 24 HCPs and 288 patients. The 5‐to‐7‐day PGx results turnaround time was acceptable to HCP (100%) and patients (69%). Most HCPs (92%) indicated that it was appropriate for the PGx clinical pharmacist to provide results to patients. Patients reported equal preference for receiving PGx results from a doctor/pharmacist. Patients and HCPs highly rated the pharmacist‐led PGx service. HCPs were overall accepting of the program, with the majority (96%) willing to offer PGx testing to their patients beyond the trial. HCPs identified that lack of financial reimbursements (62%) and lack of infrastructure (38%) were the main reasons likely to prevent/slow the implementation of PGx screening program into routine clinical care. Survey data have shown overall acceptability from patients and HCPs participating in the PGx Program. Barriers to implementation of PGx testing in routine care have been identified, providing opportunity to develop targeted implementation strategies for scaled translation into routine practice.

Abstract Objective Duchenne muscular dystrophy (DMD) is a neuromuscular disorder in which many patients also have neurobehavioral problems. Corticosteroids, the primary pharmacological treatment for DMD, have been shown to affect brain morphology in other conditions, but data in DMD are lacking. This study aimed to investigate the impact of two corticosteroid regimens on brain volumetrics in DMD using magnetic resonance imaging (MRI). Methods In a cross‐sectional, two‐center study, T1‐weighted MRI scans were obtained from three age‐matched groups (9–18 years): DMD patients treated daily with deflazacort (DMDd, n = 20, scan site: Leuven), DMD patients treated intermittently with prednisone (DMDi, n = 20, scan site: Leiden), and healthy controls (n = 40, both scan sites). FSL was used to perform voxel‐based morphometry analyses and to calculate intracranial, total brain, gray matter, white matter, and cerebrospinal fluid volumes. A MANCOVA was employed to compare global volumetrics between groups, with site as covariate. Results Both patient groups displayed regional differences in gray matter volumes compared to the control group. The DMDd group showed a wider extent of brain regions affected and a greater difference overall. This was substantiated by the global volume quantification: the DMDd group, but not the DMDi group, showed significant differences in gray matter, white matter, and cerebrospinal fluid volumes compared to the control group, after correction for intracranial volume. Interpretation Volumetric differences in the brain are considered part of the DMD phenotype. This study suggests an additional impact of corticosteroid treatment showing a contrast between pronounced alterations seen in patients receiving daily corticosteroid treatment and more subtle differences in those treated intermittently.

Abstract Aims To evaluate a whole‐food diet strategy (the Monash Pouch diet [MPD]) designed based on the interacting roles dietary factors play with pouch health. Specifically, its tolerability and acceptability, whether it achieved its dietary and metabolic goals, and the effects on symptoms and inflammation were examined. Methods In a 6‐week open‐label trial, patients with ileoanal pouches educated on the MPD were assessed regarding diet tolerability and acceptance, food intake (7‐day food diaries), pouch‐related symptoms (clinical pouchitis disease activity index), and, in 24‐h fecal samples, calprotectin, fermentative biomarkers, and volatile organic compounds (VOC). Results Of 12 patients, 6 male, mean (SD) age 55 (5) and pouch age 13 (2) years, one withdrew with partial small bowel obstruction. Tolerability was excellent in 9 (75%) and acceptance was high (81%). Targeted changes in dietary intake were achieved. Fecal branched‐ to short‐chain fatty acid ratio increased by median 60 [IQR: 11–80]% (P = 0.02). Fecal VOCs for 3 compounds were also increased, 2‐methyl‐5‐propan‐2‐ylcyclohexa‐1,3‐diene (Fold‐change [FC] 2.08), 1,3,3‐trimethyl‐2‐oxabicyclo[2.2.2]octane (FC 3.86), propan‐2‐ol (FC 2.10). All six symptomatic patients achieved symptomatic remission (P = 0.03). Fecal calprotectin at baseline was 292 [176–527] μg/g and at week 5 was 205 [148–310] μg/g (P = 0.72). Conclusion Well tolerated and accepted, the MPD achieved targeted changes in intakes and fermentation of carbohydrates relative to that of protein. There were signals of improvement in symptoms. These results indicate the need for a randomized‐controlled trial. (Trial registration: ACTRN12621000374864; https://www.anzctr.org.au/ACTRN12621000374864.aspx).

Abstract Respiratory syncytial virus (RSV) causes substantial morbidity and mortality in infants, the immunocompromised, and the elderly. RSV infects the airway epithelium via the apical membrane and almost exclusively sheds progeny virions back into the airway mucus (AM), making RSV difficult to target by systemically administered therapies. An inhalable “muco‐trapping” variant of motavizumab (Mota‐MT), a potent neutralizing mAb against RSV F is engineered. Mota‐MT traps RSV in AM via polyvalent Fc‐mucin bonds, reducing the fraction of fast‐moving RSV particles in both fresh pediatric and adult AM by ≈20–30‐fold in a Fc‐glycan dependent manner, and facilitates clearance from the airways of mice within minutes. Intranasal dosing of Mota‐MT eliminated viral load in cotton rats within 2 days. Daily nebulized delivery of Mota‐MT to RSV‐infected neonatal lambs, beginning 3 days after infection when viral load is at its maximum, led to a 10 000‐fold and 100 000‐fold reduction in viral load in bronchoalveolar lavage and lung tissues relative to placebo control, respectively. Mota‐MT‐treated lambs exhibited reduced bronchiolitis, neutrophil infiltration, and airway remodeling than lambs receiving placebo or intramuscular palivizumab. The findings underscore inhaled delivery of muco‐trapping mAbs as a promising strategy for the treatment of RSV and other acute respiratory infections.

Abstract Conservation funding is currently limited; cost‐effective conservation solutions are essential. We suggest that the thousands of field stations worldwide can play key roles at the frontline of biodiversity conservation and have high intrinsic value. We assessed field stations’ conservation return on investment and explored the impact of COVID‐19. We surveyed leaders of field stations across tropical regions that host primate research; 157 field stations in 56 countries responded. Respondents reported improved habitat quality and reduced hunting rates at over 80% of field stations and lower operational costs per km2 than protected areas, yet half of those surveyed have less funding now than in 2019. Spatial analyses support field station presence as reducing deforestation. These “earth observatories” provide a high return on investment; we advocate for increased support of field station programs and for governments to support their vital conservation efforts by investing accordingly.

Abstract Native wild flowering plants provide important season‐round nectar and pollen resources for flower‐visiting insects, but many are unappreciated or even disliked by members of the public; for example ivy (Hedera spp.), dandelion (Taraxacum officinale agg.) and bramble (Rubus fruticosus agg.). This antipathy has received little research attention despite a pressing need for a societal shift towards greater awareness of such plants and recognition of their ecological value. Engendering greater awareness and appreciation of common wild‐growing plants could greatly improve floral resource availability for flower‐visiting insects, enhance biodiversity and simultaneously benefit human physical and mental well‐being. However, there are multiple challenges to changing public attitudes. Knowledge of common wild flowering plants among members of the public is limited and this phenomenon is symptomatic of a diminishing human connection to nature. While many species of wild flowering plants may be overlooked due to a lack of awareness or knowledge, it is evident that some ‘weeds’ are actively unpopular. Reframing societal perceptions towards ecological value could be achieved in several ways including through formal education, messaging by the media, businesses and environmental organisations, and by encouraging public participation in urban land management. Read the free Plain Language Summary for this article on the Journal blog.

Abstract Recent marine heatwaves in the Gulf of Alaska have had devastating impacts on species from various trophic levels. Due to climate change, total heat exposure in the upper ocean has become longer, more intense, more frequent, and more likely to happen at the same time as other environmental extremes. The combination of multiple environmental extremes can exacerbate the response of sensitive marine organisms. Our hindcast simulation provides the first indication that more than 20% of the bottom water of the Gulf of Alaska continental shelf was exposed to quadruple heat, positive hydrogen ion concentration [H+], negative aragonite saturation state (Ωarag), and negative oxygen concentration [O2] compound extreme events during the 2018–2020 marine heat wave. Natural intrusion of deep and acidified water combined with the marine heat wave triggered the first occurrence of these events in 2019. During the 2013–2016 marine heat wave, surface waters were already exposed to widespread marine heat and positive [H+] compound extreme events due to the temperature effect on the [H+]. We introduce a new Gulf of Alaska Downwelling Index (GOADI) with short‐term predictive skill, which can serve as indicator of past and near‐future positive [H+], negative Ωarag, and negative [O2] compound extreme events near the shelf seafloor. Our results suggest that the marine heat waves may have not been the sole environmental stressor that led to the observed ecosystem impacts and warrant a closer look at existing in situ inorganic carbon and other environmental data in combination with biological observations and model output.

Abstract Introduction Research driven by real‐world clinical data is increasingly vital to enabling learning health systems, but integrating such data from across disparate health systems is challenging. As part of the NCATS National COVID Cohort Collaborative (N3C), the N3C Data Enclave was established as a centralized repository of deidentified and harmonized COVID‐19 patient data from institutions across the US. However, making this data most useful for research requires linking it with information such as mortality data, images, and viral variants. The objective of this project was to establish privacy‐preserving record linkage (PPRL) methods to ensure that patient‐level EHR data remains secure and private when governance‐approved linkages with other datasets occur. Methods Separate agreements and approval processes govern N3C data contribution and data access. The Linkage Honest Broker (LHB), an independent neutral party (the Regenstrief Institute), ensures data linkages are robust and secure by adding an extra layer of separation between protected health information and clinical data. The LHB's PPRL methods (including algorithms, processes, and governance) match patient records using “deidentified tokens,” which are hashed combinations of identifier fields that define a match across data repositories without using patients' clear‐text identifiers. Results These methods enable three linkage functions: Deduplication, Linking Multiple Datasets, and Cohort Discovery. To date, two external repositories have been cross‐linked. As of March 1, 2023, 43 sites have signed the LHB Agreement; 35 sites have sent tokens generated for 9 528 998 patients. In this initial cohort, the LHB identified 135 037 matches and 68 596 duplicates. Conclusion This large‐scale linkage study using deidentified datasets of varying characteristics established secure methods for protecting the privacy of N3C patient data when linked for research purposes. This technology has potential for use with registries for other diseases and conditions.

Abstract The COVID‐19 pandemic led to increased telehealth utilization in outpatient otolaryngology settings. While other studies on telehealth usage in otolaryngology settings have focused on demographic disparities during the pandemic, none have yet assessed how these demographic disparities have evolved from before versus after the pandemic. This study examines 4 recent consecutive years of demographic and clinical data from a large hospital system to investigate how the COVID‐19 pandemic has changed demographic patterns in telehealth utilization. We demonstrate substantial increases in the number of otolaryngology patients participating in telehealth since the beginning of the COVID‐19 pandemic but with no differences in patient distributions by race or ethnicity over time. We also found that telehealth patients, on average, were younger, more likely to be English‐speaking, and more likely to be female. While these disparities widened slightly after the start of the pandemic, they were also present prior to the pandemic.

Abstract Ayahuasca is a psychedelic plant brew originating from the Amazon rainforest. It is formed from two basic components, the Banisteriopsis caapi vine and a plant containing the potent psychedelic dimethyltryptamine (DMT), usually Psychotria viridis. Here we review the history of ayahuasca and describe recent work on its pharmacology, phenomenological responses, and clinical applications. There has been a significant increase in interest in ayahuasca since the turn of the millennium. Anecdotal evidence varies significantly, ranging from evangelical accounts to horror stories involving physical and psychological harm. The effects of the brew on personality and mental health outcomes are discussed in this review. Furthermore, phenomenological analyses of the ayahuasca experience are explored. Ayahuasca is a promising psychedelic agent that warrants greater empirical attention regarding its basic neurochemical mechanisms of action and potential therapeutic application.

Abstract The Centre for Marine Evolutionary Biology (CeMEB) at the University of Gothenburg, Sweden, was established in 2008 through a 10‐year research grant of 8.7 m€ to a team of senior researchers. Today, CeMEB members have contributed >500 scientific publications, 30 PhD theses and have organised 75 meetings and courses, including 18 three‐day meetings and four conferences. What are the footprints of CeMEB, and how will the centre continue to play a national and international role as an important node of marine evolutionary research? In this perspective article, we first look back over the 10 years of CeMEB activities and briefly survey some of the many achievements of CeMEB. We furthermore compare the initial goals, as formulated in the grant application, with what has been achieved, and discuss challenges and milestones along the way. Finally, we bring forward some general lessons that can be learnt from a research funding of this type, and we also look ahead, discussing how CeMEB’s achievements and lessons can be used as a springboard to the future of marine evolutionary biology.

Abstract Introduction There are few meaningful frameworks or toolkits that exist for involvement with young people. Coproduction is a more recent patient and public involvement (PPI) approach that emphasizes the importance of power‐sharing, to set young people as equal partners in the research process. This paper explores the successes and challenges encountered by one coproduced PPI space for young people. Methods This paper is written by a team of young people who developed and worked on the Youth PPI Café over a period of 18 months. It explores how we developed a youth‐led space for involvement in research. The authors have reflected on their experiences, providing examples of how youth PPI and coproduction were delivered in the NHS, in practice. Results By working ‘with’ young people, rather than ‘for’ them, we offer insights into the successes and challenges of an entirely youth‐led involvement space. Despite being effective in shaping mental health research for children and young people, we faced challenges with tokenism, resourcing and diversity and inclusion. Conclusions Involving youth meaningfully in research has the potential to inform studies at a macro‐ and microlevel, enabling positive change within research and within the systems that support young people. Patient or Public Contribution Young people aged 16–24 years with lived experience were included at every stage of this project, from formulation to the delivery and development of the group, to the preparation of this manuscript and its dissemination. Sussex Partnership NHS Foundation Trust's charity ‘Heads On’ provided funding for this study.

Abstract Complexity theory predicts that self‐organized, regularly patterned ecosystems store more biomass and are more resilient than spatially uniform systems. Self‐organized ecosystems are well‐known from the terrestrial realm, with “tiger bushes” being the archetypical example and mussel beds and tropical coral reefs the marine examples. We here identify regular spatial patterns in cold‐water coral reefs (nicknamed “tiger reefs”) from video transects and argue that these are likely the result of self‐organization. We used variograms and Lomb–Scargle analysis of seven annotated video transects to analyze spatial patterns in live coral and dead coral (i.e., skeletal remains) cover at the Logachev coral mound province (NE Atlantic Ocean) and found regular spatial patterns with length scales between 62 and 523 m in live and dead coral distribution along these transects that point to self‐organization of cold‐water coral reefs. Self‐organization theory shows that self‐organized ecosystems can withstand large environmental changes by adjusting their spatial configuration. We found indications that cold‐water corals can similarly adjust their spatial configuration, possibly providing resilience in the face of climate change. Dead coral framework remains in the environment for extended periods of time, providing a template for spatial patterns that facilitates live coral recovery. The notion of regular spatial patterns in cold‐water coral reefs is interesting for cold‐water coral restoration, as transplantation will be more successful when it follows the patterns that are naturally present. This finding also underlines that anthropogenic effects such as ocean acidification and bottom trawling that destroy the dead coral template undermine cold‐water coral resilience. Differences in the pattern periodicities of live and dead coral cover further present an interesting new angle to investigate past and present environmental conditions in cold‐water coral reefs.

Abstract Background Formulating sophisticated fluid therapy plans can be complicated and time consuming. Consequently, veterinarians in the field who lack experience, time, or confidence may formulate suboptimal fluid therapy plans. Objectives Compare conventional and app‐guided fluid therapy plans for simulated cases of neonatal calf diarrhea. Participants Third and fourth year veterinary students (n = 55) from The University of Sydney. Methods We developed a web app to assist fluid therapy formulation (http://calfaid.com) that was evaluated in a randomized case simulation trial. Participants were instructed to perform fluid therapy calculations and formulate an integrated fluid therapy plan for case scenarios using conventional methods and using the fluid therapy app. Responses were scored by a blinded study investigator using an a priori scoring guide and groups (conventional vs. app‐guided) were compared using linear mixed models. Results On average, total scores for app‐guided fluid therapy calculations were 20.6% points higher (95% confidence interval [CI], 14.1‐27.1) than calculations completed using the conventional method (88.2% vs. 67.5%, respectively). On average, total scores for app‐guided integrated fluid therapy plans were 14.2% points higher (95% CI, 6.3‐22.2; 65.8% vs. 51.2%). Eighty percent of respondents indicated they would prefer to use the app‐guided method over the conventional method. Conclusion and Clinical Importance Our findings suggest that fluid therapy plans can be improved using apps.

Abstract Aims Optimal management of heart failure with reduced ejection fraction (HFrEF) includes titration of guideline‐directed medical therapy (GDMT) to the highest tolerated dose within the licensed range. During hospitalization, GDMT doses are often significantly altered, although it is unknown whether the cause of hospitalization influences this. Methods and results We recruited 711 people with stable HFrEF from specialist heart failure clinics and prospectively assessed events occurring during first unplanned hospitalization. Dose changes of ACE inhibitors or angiotensin receptor blockers (ACEi/ARB), beta‐blockers, mineralocorticoid receptor antagonists, and loop diuretics were recorded during 414 hospitalizations, categorized as due to decompensated heart failure, other cardiovascular causes, infection, or other non‐cardiovascular causes. Most hospitalizations resulted in no change to GDMT. ACEi/ARB dose was reduced in 21% of hospitalizations and was more common during non‐cardiovascular hospitalization (25.4% vs. 13.9%; P = 0.005). ACEi/ARB dose reduction was associated with older age and lower left ventricular ejection fraction at study recruitment, and poorer renal function, lower systolic blood pressure, higher serum potassium, and less frequent care from a cardiologist during admission. People experiencing ACEi/ARB reduction had worse age‐adjusted survival after discharge, without differences in heart failure re‐hospitalization. De‐escalation of beta‐blockers occurred in 8% of hospitalizations, most often due to other non‐cardiovascular causes; this was not associated with post‐discharge survival or re‐hospitalization with heart failure. Conclusions De‐escalation of HFrEF GDMT is more common during non‐cardiovascular hospitalization and for ACEi/ARB is associated with reduced survival. Post‐discharge care plans should include robust plans to consider re‐escalation of GDMT in these cases.

Abstract Aims Understanding of the pathophysiology of progressive heart failure (HF) in patients with heart failure with preserved ejection fraction (HFpEF) is incomplete. We sought to identify factors differentially associated with risk of progressive HF death and hospitalization in patients with HFpEF compared with patients with HF and reduced ejection fraction (HFrEF). Methods and results Prospective cohort study of patients newly referred to secondary care with suspicion of HF, based on symptoms and signs of HF and elevated natriuretic peptides (NP), followed up for a minimum of 6 years. HFpEF and HFrEF were diagnosed according to the 2016 European Society of Cardiology guidelines. Of 960 patients referred, 467 had HFpEF (49%), 311 had HFrEF (32%), and 182 (19%) had neither. Atrial fibrillation (AF) was found in 37% of patients with HFpEF and 34% with HFrEF. During 6 years follow‐up, 19% of HFrEF and 14% of HFpEF patients were hospitalized or died due to progressive HF, hazard ratio (HR) 0.67 (95% CI: 0.47–0.96; P = 0.028). AF was the only marker that was differentially associated with progressive HF death or hospitalization in patients with HFpEF HR 2.58 (95% CI: 1.59–4.21; P

Abstract For Li‐Se batteries, cathode using carbonaceous hosts to accommodate Se performed modestly, whereas those applying metallic compounds with stronger chemical adsorption exhibited even more rapid capacity decay, the intrinsic reasons for which are still not clear. Herein, it is found that Se tends to precipitate on the surface of the electrode during cycling, and the precipitation speed depends on the polarization degree of the host. A further enhanced adsorption does not certainly generate better electrochemical activity, since hosts with overhigh adsorption ability are hard to desorb polyselenides, leading to catalyst passivation and rapid capacity decay. These findings encourage us to design a ternary anatase/rutile/titanium nitride (aTiO2/rTiO2/TiN@C) composite host, integrating good adsorption of TiO2 and rapid electron transport ability of TiN, and introducing rutile to weaken overall adsorption. The aTiO2/rTiO2/TiN@C composite with medium adsorption not only avoids rapid loss of active substances in electrolyte but also slows down the precipitation speed of Se. As a result, the aTiO2/rTiO2/TiN@C/Se electrode delivered good rate capability(154 mA h g−1 at 20 C) and good cycling stability(a low decay of 0.024% per cycle within 500 cycles at 2 C).

Abstract Seismic moment and rupture length can be combined to infer stress drop, a key parameter for assessing earthquakes. In natural earthquakes, stress drops are largely depth‐independent, which is surprising given the expected dependence of frictional stress on normal stresses and hence overburden. We have developed a transparent experimental fault that allows direct observation of thousands of slip events, with ruptures that are fully contained within the fault. Surprisingly, the observed stress drops are largely independent of both the magnitude of normal stress and its heterogeneity, capturing the independence seen in nature. However, we observe larger, normal stress‐dependent stress drops when the fault area is reduced, which allows slip events to frequently reach the edge of the interface. We conclude that confined ruptures have normal stress independent stress drops, and thus the depth‐independent stress drops of tectonic earthquakes may be a consequence of their confined nature.

Background Patients with Brugada syndrome (BrS) are recommended to avoid drugs that may increase their risk of arrhythmic events. We examined treatment with such drugs in patients with BrS after their diagnosis. Methods and Results All Danish patients diagnosed with BrS (2006–2018) with >12 months of follow‐up were identified from nationwide registries. Nonrecommended BrS drugs were grouped into drugs to “avoid” or “preferably avoid” according to http://www.brugadadrugs.org. Cox proportional hazards analyses were performed to identify factors associated with any nonrecommended BrS drug use, and logistic regression analyses were performed to examine associated risk of appropriate implantable cardioverter defibrillator therapy, mortality, and a combined end point indicating an arrhythmic event of delayed implantable cardioverter defibrillator implantation, appropriate implantable cardioverter defibrillator therapy, and mortality. During a median follow‐up of 6.8 years, 93/270 (34.4%) patients with BrS (70.4% male, median age at diagnosis 46.1 years [interquartile range, 32.6–57.4]) were treated with ≥1 nonrecommended BrS drugs. No difference in any nonrecommended BrS drug use was identified comparing time before BrS diagnosis (12.6%) with each of the 5 years following BrS diagnosis (P>0.05). Factors associated with any nonrecommended BrS drug use after diagnosis were female sex (hazard ratio [HR]) 1.83 [95% CI, 1.15–2.90]), psychiatric disease (HR, 3.63 [1.89–6.99]), and prior use of any nonrecommended BrS drug (HR, 4.76 [2.45–9.25]). No significant association between any nonrecommended BrS drug use and implantable cardioverter defibrillator therapy (n=20/97, odds ratio [OR], 0.7 [0.2–2.4]), mortality (n=10/270, OR, 3.4 [0.7–19.6]), or the combined end point (n=38/270, OR, 1.7 [0.8–3.7]) was identified. Conclusions One in 3 patients with BrS were treated with a nonrecommended BrS drug after BrS diagnosis, and a BrS diagnosis did not change prescription patterns. More awareness of nonrecommended drug use among patients with BrS is needed.

Abstract Background The SlowMo study demonstrated the effects of SlowMo, an eight‐session digitally supported reasoning intervention, on paranoia in a large‐scale randomized‐controlled trial with 362 participants with schizophrenia‐spectrum psychosis. Aim The current evaluation aimed to investigate the impact of Patient and Public Involvement (PPI) in the SlowMo study. Method PPI members were six women and three men from Sussex, Oxford and London with experience of using mental health services for psychosis. They received training and met at least 3‐monthly throughout the project. The impact of PPI was captured quantitatively and qualitatively through (i) a PPI log of recommendations and implementation; (ii) written subjective experiences of PPI members; (iii) meeting minutes; and (iv) outputs produced. Results The PPI log revealed 107 recommendations arising from PPI meetings, of which 87 (81%) were implemented. Implementation was greater for recruitment‐, data collection‐ and organization‐related actions than for dissemination and emergent innovations. Qualitative feedback revealed impacts on study recruitment, data collection, PPI participants' confidence, knowledge, career aspirations and society more widely. Outputs produced included a film about psychosis that aired on BBC primetime television, novel webpages and journal articles. Barriers to PPI impact included geography, travel, funding, co‐ordination and well‐being. Discussion A future challenge for PPI impact will be the extent to which peer innovation (innovative PPI‐led ideas) can be supported within research study delivery. Patient and Public Contribution Planned Patient and Public Contribution in SlowMo comprised consultation and collaboration in (i) design, (ii) recruitment, (iii) qualitative interviews and analysis of service users' experiences of SlowMo therapy and (iv) dissemination.

Abstract Although microbial communities of insects from larval to adult stage have been increasingly investigated in recent years, little is still known about the diversity and composition of egg‐associated microbiomes. In this study, we used high‐throughput amplicon sequencing and quantitative PCR to get a better understanding of the microbiome of insect eggs and how they are established using the Southern green stinkbug Nezara viridula (L.) (Hemiptera: Pentatomidae) as a study object. First, to determine the bacterial community composition, egg masses from two natural populations in Belgium and Italy were examined. Subsequently, microbial community establishment was assessed by studying stinkbug eggs of different ages obtained from laboratory strains (unlaid eggs collected from the ovaries, eggs less than 24 h old, and eggs collected 4 days after oviposition). Both the external and internal egg‐associated microbiomes were analyzed by investigating egg washes and surface‐sterilized washed eggs, respectively. Eggs from the ovaries were completely devoid of bacteria, indicating that egg‐associated bacteria were deposited on the eggs during or after oviposition. The bacterial diversity of deposited eggs was very low, with on average 6.1 zero‐radius operational taxonomic units (zOTUs) in the external microbiome and 1.2 zOTUs in internal samples of egg masses collected from the field. Bacterial community composition and density did not change significantly over time, suggesting limited bacterial growth. A Pantoea‐like symbiont previously found in the midgut of N. viridula was found in every sample and generally occurred at high relative and absolute densities, especially in the internal egg samples. Additionally, some eggs harbored a Sodalis symbiont, which has previously been found in the abdomen of several insects, but so far not in N. viridula populations. We conclude that the egg‐associated bacterial microbiome of N. viridula is species‐poor and dominated by a few symbionts, particularly the species‐specific obligate Pantoea‐like symbiont.

Background New‐onset postoperative atrial fibrillation (POAF) develops in approximately one‐third of patients undergoing cardiac surgery and is associated with a higher incidence of ischemic stroke and increased mortality. However, it remains unknown to what extent ischemic stroke events in patients with POAF are cardioembolic and whether anticoagulant therapy is indicated. We investigated the long‐term risk and pathogenesis of postoperative stroke in patients undergoing coronary artery bypass grafting experiencing POAF. Methods and Results This was a register‐based cohort study. Data from the WDHR (Western Denmark Heart Registry) were linked with the DNPR (Danish National Patient Register), the Danish National Prescription Register, and the Cause of Death Register. All stroke diagnoses were verified, and ischemic stroke cases were subclassified according to pathogenesis. Furthermore, investigations of all‐cause mortality and the use of anticoagulation medicine for the individual patient were performed. A total of 7813 patients without a preoperative history of atrial fibrillation underwent isolated coronary artery bypass grafting between January 1, 2010, and December 31, 2018, in Western Denmark. POAF was registered in 2049 (26.2%) patients, and a postoperative ischemic stroke was registered in 195 (2.5%) of the patients. After adjustment, there was no difference in the risk of ischemic stroke (hazard ratio [HR], 1.08 [95% CI, 0.74–1.56]) or all‐cause mortality (HR, 1.09 [95% CI, 0.98–1.23]) between patients who developed POAF and non‐POAF patients. Although not statistically significant, patients with POAF had a higher incidence rate (IR; per 1000 patient‐years) of cardioembolic stroke (IR, 1 [95% CI, 0.6–1.6] versus IR, 0.5 [95% CI, 0.3–0.8]), whereas non‐POAF patients had a higher incidence rate of large‐artery occlusion stroke (IR, 1.1 [95% CI, 0.8–1.5] versus IR, 0.7 [95% CI, 0.4–1.4]). Early initiation of anticoagulation medicine was not associated with a lower risk of ischemic stroke. However, patients with POAF were more likely to die of cardiovascular causes than non‐POAF patients (P

Background Angiotensin receptor neprilysin inhibitors (ARNI) reduce mortality and hospitalization for patients with heart failure. However, relatively high copayments for ARNI may contribute to suboptimal adherence, thus potentially limiting their benefits. Methods and Results We conducted a retrospective cohort study within a large, multi‐site health system. We included patients with: ARNI prescription between November 20, 2020 and June 30, 2021; diagnosis of heart failure or left ventricular ejection fraction ≤40%; and available pharmacy or pharmacy benefit manager copayment data. The primary exposure was copayment, categorized as $0, $0.01 to $10, $10.01 to $100, and >$100. The primary outcome was prescription fill nonadherence, defined as the proportion of days covered $100. Patients with higher copayments had higher rates of nonadherence, ranging from 17.2% for $0 copayment to 34.2% for copayment >$100 (P$100 (OR, 2.58 [95% CI, 1.63–4.18], P

Abstract Non‐invasive procedures are needed for prostate cancer management, and urine represents a potential source of new biomarkers with translational value. Recent evidence has shown that the growth of new nerves in the tumor microenvironment is essential to prostate cancer progression. Neurotrophic growth factors are expressed by prostate cancer cells and contribute to prostate tumor innervation, but their presence in urine is unclear. In the present study, we have assayed the concentration of neurotrophic factors in the urine of prostate cancer patients. Urine was collected from a prospective cohort of 45 men with prostate cancer versus 30 men without cancer and enzyme‐linked immunosorbent assay was used to quantify nerve growth factor (NGF) and its precursor proNGF, brain‐derived neurotrophic factor (BDNF) and proBDNF, neurotrophin‐3, neurotrophin‐4/5, and glia‐derived neurotrophic growth factor. The results show that neurotrophic factors are detectable in various concentrations in both cancer and healthy urine, but no significant difference was found. Also, no association was observed between neurotrophic factor concentrations and prostate cancer grade. This study is the first quantification of neurotrophins in urine, and although no significant differences were observed between prostate cancer patients versus those without prostate cancer, or between prostate cancers of various grades, the potential value of neurotrophins for prostate cancer diagnosis and prognosis warrants further investigations in larger patient cohorts.

Abstract Objective We conducted a UK‐wide survey to identify the top 10 research questions for young people's cancer. We conducted secondary analysis of questions submitted, which were ‘out‐of‐scope’ of the original survey aim. We sought to disseminate these questions, to inform practice, policy and the development of potential interventions to support young people with cancer. Design James Lind Alliance Priority Setting Partnership. Participants Young people aged 13‐24 with a current/previous cancer diagnosis, their families/friends/partners and professionals who work with this population. Methods Eight hundred and fifty‐five potential research questions were submitted, and 326 were classified as ‘out‐of‐scope’. These questions, along with 49 ‘free‐text’ comments, were analysed using thematic analysis. Results The 375 out‐of‐scope questions and comments were submitted by: 68 young people, 81 family members/partners/friends and 42 professionals. Ten overarching themes were identified: diagnostic experience; communication; coordination of care; information needs and lack of information; service provision; long‐term effects and aftercare support; family support; financial impact; end‐of life care; and research methods and current research. Conclusions The need to tailor services, information and communication is a striking thread evidenced across the ‘out‐of‐scope’ questions. Gaps in information highlight implications for practice in revisiting information needs throughout the cancer trajectory. We must advocate for specialist care for young people and promote the research priorities and these findings to funding bodies, charities, young people and health and social care policymakers, in order to generate an evidence base to inform effective interventions across the cancer trajectory and improve outcomes. Patient/public contributions Patients and carers were equal stakeholders throughout.