Search

Abstract Resistance training (RT) is the gold standard intervention for ameliorating sarcopenia. Outstanding mechanistic questions remain regarding the malleability of the molecular determinants of skeletal muscle function in older age. Discovery of proteomics can expand such knowledge. We aimed to compare the effect of RT on the skeletal muscle proteome and neuromuscular function (NMF) in older and younger women. Seven young (22 ± 6 years) and eight older (63 ± 5 years) women completed 8 weeks’ leg RT. Pre‐ and post‐training, measures of leg and handgrip strength, NMF and vastus lateralis (VL) biopsies were obtained. Tandem‐mass‐tagged skeletal muscle proteomic analyses were performed. Data were analysed using differential expression and weighted gene co‐expression network approaches. Proteins related to skeletal muscle contraction were lower in older skeletal muscle; this was not normalised by RT. Following RT, older women had higher expression of VL mitochondrial biogenesis proteins compared to the young, a reversal of pre‐training observations. Seventy proteins were differentially expressed between age groups. VL expression of these proteins in older women was consistently and significantly associated with poorer leg strength/NMF. Conversely, VL expression of these proteins in older women was often associated with greater handgrip strength. This study has identified important differences in the molecular responses of young and old skeletal muscle to RT. We have demonstrated their close relationship with skeletal muscle function. Proteins that are refractory to RT may represent targets to ameliorate sarcopenia. We have described a ‘proteomic‐function’ relationship that appears to be muscle‐specific. Future research should further unpick these complex relationships.

Abstract How young people interpret and engage with nature is an important consideration within our current biodiversity and climate crises. What remains less clear are the ways in which online, networked, spaces underpin young people's relationships with nature, and what consequences these spaces may have for in‐person nature interactions. Given the ubiquitousness of networked spaces in society, it has been argued that day‐to‐day life is increasingly ‘postdigital’, in that we may no longer distinguish meaningful differences between our online and offline worlds. Therefore, it is necessary to examine this collapsing physical‐digital binary in the context of young people's in‐person interactions with nature to examine the effectiveness of this theoretical perspective. Utilising ethnographically situated, participant‐as‐observer methods, this qualitative multiple case study generated data across three rural residential outdoor education centres in England, Scotland and Wales, with young people aged 12–17. Participants were visiting the residential centres from urban schools in England and Scotland, with each group spending 5 days at their respective centre. Reflexive thematic analysis of fieldnote data revealed that young people had previously constructed their understandings and interpretations of what nature ‘is’ through networked environments such as Instagram, TikTok and Minecraft. These networked constructions often contextualised young people's direct, in‐person interactions with nature and demonstrated ways in which these online spaces influenced how nature was perceived and understood. The case is presented for interpreting the findings from a postdigital ‘networked baselines’ perspective. The findings will resonate with practitioners and policymakers concerned with the relationships between young people, networked spaces and nature connectedness. Alongside this, given the editorial discussion on the impacts of ‘nature on screen’ from Silk et al. (2021) in People and Nature, this paper provides a set of empirical findings on how young people's organic engagements with nature on‐screen provided a degree of foundational knowledge about what nature is, what nature is for and how nature should be engaged with. Read the free Plain Language Summary for this article on the Journal blog.

Abstract The vagus nerve is a key mediator of brain–heart signaling, and its activity is necessary for cardiovascular health. Vagal outflow stems from the nucleus ambiguus, responsible primarily for fast, beat‐to‐beat regulation of heart rate and rhythm, and the dorsal motor nucleus of the vagus, responsible primarily for slow regulation of ventricular contractility. Due to the high‐dimensional and multimodal nature of the anatomical, molecular and physiological data on neural regulation of cardiac function, data‐derived mechanistic insights have proven elusive. Elucidating insights has been complicated further by the broad distribution of the data across heart, brain and peripheral nervous system circuits. Here we lay out an integrative framework based on computational modelling for combining these disparate and multi‐scale data on the two vagal control lanes of the cardiovascular system. Newly available molecular‐scale data, particularly single‐cell transcriptomic analyses, have augmented our understanding of the heterogeneous neuronal states underlying vagally mediated fast and slow regulation of cardiac physiology. Cellular‐scale computational models built from these data sets represent building blocks that can be combined using anatomical and neural circuit connectivity, neuronal electrophysiology, and organ/organismal‐scale physiology data to create multi‐system, multi‐scale models that enable in silico exploration of the fast versus slow lane vagal stimulation. The insights from the computational modelling and analyses will guide new experimental questions on the mechanisms regulating the fast and slow lanes of the cardiac vagus toward exploiting targeted vagal neuromodulatory activity to promote cardiovascular health.

Abstract Background Enteral nutrition (EN) is essential for management of hepatic lipidosis (HL) in cats. Objectives To determine if time to start of EN and other clinicopathologic variables are associated with outcome in cats with HL. Animals Forty‐eight cats with HL. Methods Retrospective study. Information retrieved from medical records and client communications included clinicopathologic findings, time to start of EN, initial % of resting energy requirements provided, type of feeding tube, duration of hospitalization, and 3‐month survival. Variables were compared between surviving and nonsurviving cats and between cats fed ≤12 hours and >12 hours after hospital admission. Multivariable statistical testing was performed to further investigate variables of interest. Results Seventeen of 25 (68%) cats fed ≤12 hours and 13 of 23 (57%) of cats fed >12 hours after hospital admission survived (P = .55). Only increasing age (odds ratio [OR], 1.313; 95% confidence interval [CI], 1.032‐1.671; P = .03) and the presence of ascites (OR, 6.415; 95% CI, 1.354‐30.395; P = .02) were associated with death in multivariable analysis. Hospitalization duration (median, interquartile range [IQR]) was shorter in cats fed >12 hours (2.8 days; IQR, 2.1‐3.8 days) as compared with cats fed ≤12 hours (4.8 days; IQR, 3.6‐6.2 days) after hospital admission (P

Abstract Maternal asthma is associated with increased rates of neonatal lung disease, and fetuses from asthmatic ewes have fewer surfactant‐producing cells and lower surfactant‐protein B gene (SFTPB) expression than controls. Antenatal betamethasone increases lung surfactant production in preterm babies, and we therefore tested this therapy in experimental maternal asthma. Ewes were sensitised to house dust mite allergen, and an asthmatic phenotype induced by fortnightly allergen lung challenges; controls received saline. Pregnant asthmatic ewes were randomised to receive antenatal saline (asthma) or 12 mg intramuscular betamethasone (asthma+beta) at 138 and 139 days of gestation (term = 150 days). Lambs were delivered by Caesarean section at 140 days of gestation and ventilated for 45 min before tissue collection. Lung function and structure were similar in control lambs (n = 16, 11 ewes) and lambs from asthma ewes (n = 14, 9 ewes). Dynamic lung compliance was higher in lambs from asthma+beta ewes (n = 12, 8 ewes) compared to those from controls (P = 0.003) or asthma ewes (P = 0.008). Lung expression of surfactant protein genes SFTPA (P = 0.048) and SFTPB (P

Cholangiocarcinoma (CCA) is a highly aggressive form of liver cancer and is an increasing cause of cancer‐related death worldwide. Despite its increasing incidence globally and alarming mortality, treatment options for CCA have largely remained unchanged, stressing the importance of developing new effective therapies. YAP activation is common in CCA, and its major transcriptional signaling partners are the TEAD proteins. CA3 is a small‐molecule YAP‐TEAD disrupter discovered utilizing a TEAD reporter assay. Utilizing CCA, gastric cancer cell lines, and patient‐derived xenograft models (PDX), we demonstrate that CA3 is effective in inducing cell death and delaying tumor growth in both FGFR2 fusion and wild‐type models. CA3 was associated with on‐target decreases in YAP‐TEAD target gene expression, TEAD reporter activity, and overall TEAD levels. Hippo pathway signaling was not altered as there was no change in YAP phosphorylation status in the cells exposed to CA3. RNA sequencing of gastric cancer and CCA models demonstrated upregulation of an androgen receptor–mediated transcriptional program following exposure to CA3 in five unique models tested. Consistent with this upstream regulator analysis, CA3 exposure in CCA cells was associated with increased AR protein levels, and combinatorial therapy with CA3 and androgen receptor blockade was associated with increased cancer cell death. CA3 behaves functionally as a YAP‐TEAD disrupter in the models tested and demonstrated therapeutic efficacy. Exposure to CA3 was associated with compensatory androgen receptor signaling and dual inhibition improved the therapeutic effect.

Abstract Objectives To assess the effect of bilateral orchidopexy in preventing future torsion and testicular loss in patients with intermittent testicular torsion. Secondarily, this study aims to assess the rate of pain improvement following orchidopexy. Methods This is a prospective cohort of patients. Participants were men who underwent elective bilateral orchidopexy for intermittent testicular torsion. All consecutive cases were treated by a single surgeon in a single centre between 2015 and 2023. The primary outcomes were prevention of torsion and testicular loss. The secondary outcome was the resolution or improvement in pain. Results The success rate of bilateral orchidopexy in preventing testicular loss due to torsion was 100%, at a follow‐up of mean 33.5 months. Of the 50 patients, 88% were pain‐free following orchidopexy, and 12% had an improvement in their pain. There were no cases of hydrocoele or haematoma in this series. To our knowledge, this is the largest series reported in the literature. Conclusions Elective bilateral orchidopexy prevents torsion and preserves testicular viability. Pain is resolved in most but not all cases. This is important in counselling men who are considering surgical management of intermittent torsion of the testicle.

Abstract Reconstructing past ecological population dynamics and demographic events is crucial for understanding the dynamics of ecological processes, evaluating the impact of environmental changes and making informed conservation decisions. In forest ecosystems, retrodiction (i.e. the backward projection of ecological populations) plays a pivotal role in understanding historical forest carbon levels and the factors that have influenced their variation over time, because forest demography is a major determinant of the amount of carbon stored in forest ecosystems. The persistent lack of quantitative methods has been a significant obstacle in retrodicting forest demography, especially in applications of a broad geographical scale. While there is a wealth of models for predicting future forest conditions, models that can project these conditions backward in time are scarce. This study presents reverse matrix model (RMM), an innovative retrodiction modelling approach grounded in the principles of transition matrix models. RMM is designed to deduce past demographic characteristics of ecological populations using current data, making it one of the first models capable of projecting the fine‐scale dynamics of forest demography into the past. We assessed the retrodictive performance of RMM by fitting it to a dataset of a disturbed tropical rainforest in French Guiana in 2001–2023, then comparing the retrodictions to observations back to 1983 when the disturbance occurred. We further empirically evaluated the viability of retrodiction over a defined duration by inverting the density‐dependent matrix model by Lin et al. (1996), which predicts the dynamics of northern hardwoods in the United States. The case studies demonstrate significant potential for RMM application in various domains of forestry and conservation, including ecosystem management and conservation planning, global change impact assessment and biodiversity monitoring.

Abstract Aims The viability of cardiac resynchronization therapy (CRT) in inotrope‐dependent heart failure (HF) has been a matter of debate. Methods and results We searched Medline, EMBASE, Scopus, and the Cochrane Library until 31 December 2022. Studies were included if (i) HF patients required inotropic support at CRT implantation; (ii) patients were ≥18 years old; and (iii) they provided a clear definition of ‘inotrope dependence’ or ‘inability to wean’. A meta‐analysis was performed in R (Version 3.5.1). Nineteen studies comprising 386 inotrope‐dependent HF patients who received CRT (mean age 64.4 years, 76.9% male) were included. A large majority survived until discharge at 91.1% [95% confidence interval (CI): 81.2% to 97.6%], 89.3% were weaned off inotropes (95% CI: 77.6% to 97.0%), and mean discharge time post‐CRT was 7.8 days (95% CI: 3.9 to 11.7). After 1 year of follow‐up, 69.7% survived (95% CI: 58.4% to 79.8%). During follow‐up, the mean number of HF hospitalizations was reduced by 1.87 (95% CI: 1.04 to 2.70, P

Abstract Introduction Gastrointestinal bleeding (GIB) is often encountered among patients with atrial fibrillation (AF) due to the use of anticoagulation. This study assesses disparities in GIB‐related mortality among decedents with AF in the United States. Methods GIB mortality data in patients with AF from 1999 to 2020 was queried from the CDC database. Decedent demographic information (age, sex, race and ethnicity, and geographic residence) was obtained from death certificates. We calculated age‐adjusted mortality rates (AAMRs) through the direct method and estimated the annual percentage change (APC) in mortality using log‐linear regression models. Results From 11,209 GIB‐related deaths among AF decedents, we observed an increase in AAMR from 0.12 in 1999 to 0.21 in 2020, particularly during the 2009 to 2020 period (APC +4.8, p

Abstract The Surface Water and Ocean Topography (SWOT) mission offers new insights into submesoscale ocean processes. Realizing this requires careful consideration of other geophysical signals such as the signal delay induced by water vapor in the troposphere. Over short spatial scales (

Abstract The use of model‐informed precision dosing to personalize infliximab has been shown to improve both the acquisition of concentration targets and clinical outcomes during maintenance. Current iterations of infliximab pharmacokinetic models include time‐varying covariates of drug clearance, however, not accounting for the expected improvements in the covariates can lead to indiscriminate use of higher infliximab doses and imprecise drug exposure. The aim was to identify changes in the four biomarkers associated with infliximab clearance (Xiong et al. model) and determine if integration of these dynamic changes would improve model performance during induction and early maintenance. We analyzed two cohorts of children receiving infliximab for Crohn's Disease. The Emax method was used to assess time‐varying changes in covariates. Model performance (observed vs. predicted infliximab concentrations) was evaluated using median percentage error (bias) and median absolute percentage error (precision). The combined cohorts included 239 Crohn's disease patients. We found from baseline to dose 4, the maximum changes in weight, albumin, erythrocyte sedimentation rate, and neutrophil CD64 were 4.7%, +11.7%, −62.4%, and −26.5%, respectively. We also found the use of baseline covariates alone to forecast future trough concentration was inferior to the Emax time‐varying method with a significant improvement observed in bias (doses 2, 3, and 4) and precision (doses 2 and 4). The integration of the four time‐varying biomarkers of drug clearance with pharmacokinetic modeling improved the accuracy and precision of the predictions. This novel strategy may be key to improving drug exposure, minimizing indiscriminate dosing strategies, and reducing healthcare costs.

ABSTRACT Typically, Western Science approaches the study of complex systems by examining the component parts outside of their contextual relationships. In contrast, Indigenous people continue to advocate the need for land and seascape approaches that include all aspects of life, particularly the special relationship between Kin (people), Country, and Knowledge. Globally, Indigenous people are lobbying for environmental research to take a rights‐based approach that improves economic opportunities; confers greater authority over the stewardship of Country; delivers equity in managing Country; emboldens control to integrate knowledge systems; values and promotes culture; and recognizes Indigenous self‐determination. In Australia, the National Indigenous Environment Research Network (NIERN) proposal offers a solution that supports the rights‐based approach driven by Indigenous Australians through the establishment of a community of practice guided by Indigenous researchers and Indigenous Knowledge holders. We describe this Indigenous‐led solution to the self‐determination of Indigenous environmental research priorities by exploring the concept, the authorizing environment, and the mutual benefits that could be delivered by such a network. The empowerment of Indigenous people in research is possible if an all‐of‐system approach is taken. This approach must involve Indigenous people in all decision‐making processes including the development of research priorities, the design of methodologies, the interpretation of findings, and finally the evaluation of outputs and outcomes.

Recently, a concept of proximal Berinde contractions was introduced and applied to prove the existence of coincidence best proximity points in metric spaces. In this article, we established a new approach to show that these results can be obtained from a fixed point theorem for multivalued β,L-weak contractions.

Objective Electronic health applications (apps) allow patients with rheumatoid arthritis (RA) to report patient‐reported outcomes (PROs) between visits. However, almost no data exist on patients’ report of pain between visits and how that correlates with change in function and/or modifications to medication. Methods Patients with RA from one rheumatology practice provided data as part of a study of an app. Patients answered PRO short forms using the app, including the Patient‐Reported Outcomes Measurement Information System pain interference and physical function questionnaires. Each PRO was answered every eight days. We assessed the frequency of significant worsening in pain using the minimally clinically important difference (MCID) of ≥5 points. Logistic regression assessed whether worsening in pain was associated with functional declines and/or RA medication changes. Results Among 150 patients with RA using the app, 83 patients qualified for analysis; the mean age was 62 years, and 82% were female. The median number of pain interference PROs answered per patient was 37 over 52 weeks. Using the first five pain interference PRO responses as the baseline, 60 (72%) patients experienced worsening of at least the MCID, with a median duration of 16 days. The odds ratio (OR) relating significantly worsening pain to declines in function over the next 42 days was 2.71 (95% confidence interval [CI] 1.12–6.89). Worsening pain was not significantly associated with changes to RA medication (OR 1.59, 95% CI 0.62–4.17). Conclusion Clinically significant increases in pain among patients with RA are commonly associated with reductions in function but not with RA medication changes.

Abstract In chronic lymphocytic leukemia, the reliability of next‐generation sequencing (NGS) to detect TP53 variants ≤10% allelic frequency (low‐VAF) is debated. We tested the ability to detect 23 such variants in 41 different laboratories using their NGS method of choice. The sensitivity was 85.6%, 94.5%, and 94.8% at 1%, 2%, and 3% VAF cut‐off, respectively. While only one false positive (FP) result was reported at >2% VAF, it was more challenging to distinguish true variants

ABSTRACT Purpose The prevalence of sedentary lifestyles (SL), which includes both high volumes of extended sitting behavior and a low volume of steps accumulated across the day, among older adults continues to rise contributing to increases in associated comorbidities and the loss of independence. The social, personal, and economic burdens are enormous. In recognition of the health implications of SL, current public health physical activity guidelines now emphasize the complimentary goals of sitting less by moving more. We recently completed a 6‐month weight loss (WL) study followed by 12 months of reduced contact to examine weight regain in older adults with obesity. One of the treatment conditions involved WL + a day‐long movement intervention that explicitly targeted reducing sitting time and increasing steps across the day (SitLess). Method The goal of the current study, using baseline fMRI and accelerometry data from 36 participants and advanced machine learning tools, was to determine if we could identify complex brain circuits underlying variability associated with changes in sitting time and daily steps during the 6‐month intensive phase among participants randomized to the WL + SitLess treatment condition. Models generated from these analyses produced accuracy in predicting pre–post change in both measures that exceeded 92%, suggesting a critical role for the identified brain subnetworks in explaining variability in these outcomes in response to the intervention. The identified networks comprised regions, predominantly in the default mode and sensorimotor networks, that have been extensively linked to self‐regulation and decision‐making. Finding These results provide insights into the theoretical basis of SL for older adults and in the design of future intervention research.

Up to 50% of patients with pulmonary embolism (PE) experience hemodynamic instability and approximately 70% of patients who die of PE experience an accelerated cascade of symptoms within the first hours of onset of symptoms, thus necessitating rapid evaluation and intervention. Venoarterial extracorporeal membrane oxygenation and other ventricular assist devices, depending on the hemodynamic derangements present, may be used to stabilize patients with massive PE refractory to initial therapies or with contraindications to other interventions. Given the abnormalities in both pulmonary circulation and gas exchange caused by massive PE, venoarterial extracorporeal membrane oxygenation may be considered the preferred form of mechanical circulatory support for most patients. Venoarterial extracorporeal membrane oxygenation unloads the right ventricle and improves oxygenation, which may not only help buy time until definitive treatment but may also reduce myocardial ischemia and myocardial dysfunction. This review summarizes the available clinical data on the use of mechanical circulatory support, especially venoarterial extracorporeal membrane oxygenation, in the treatment of patients with massive PE. Furthermore, this review also provides practical guidance on the implementation of this strategy in clinical practice.

Abstract Objectives Utilizing penile saturation and temperature measurements presents a promising avenue for the development of an innovative sensor system aimed at nocturnal erection detection. This study aims to determine the feasibility of erection detection with light reflection of haemoglobin (LRH), as a precursor for penile saturation measurements, as well as penile temperature by comparison with simultaneous overnight RigiScan measurements. Materials and Methods This is a proof‐of‐concept observational study on 10 healthy volunteers with a cross sectional design. A penile transdermal haemoglobin and temperature sensor was developed to measure penile LRH through real‐time monitoring with receiving photodiodes and emitting light‐emitting diode (LED). Besides statistical analysis on LRH, temperature and RigiScan data, a visual assessment was done to determine detectability of changes in the LRH and temperature course during the RigiScan‐annotated erections. Results A total of 40 nocturnal erections from 10 healthy volunteers were annotated with the RigiScan. The LRH values significantly increase during a nocturnal erection (p

Abstract Aims This study aimed to examine the diagnostic pathways and outcomes of patients with heart failure (HF), stratified by left ventricular ejection fraction (EF), and to highlight deficiencies in real‐world HF diagnosis and management. Methods and results We conducted a retrospective cohort study in Salford, United Kingdom, utilizing linked primary and secondary care data for HF patients diagnosed between January 2010 and November 2019. We evaluated characteristics, diagnostic patterns, healthcare resource utilization, and outcomes. Patients were categorized according to baseline (the latest measure prior to or within 90 days post‐diagnosis) as having HF with reduced EF (HFrEF), mildly reduced EF (HFmrEF), or preserved EF (HFpEF). The data encompassed a 2 year period before diagnosis and up to 5 years post‐diagnosis. A total of 3227 patients were diagnosed with HF between January 2010 and November 2019. The mean follow‐up time was 2.6 [±1.9 standard deviation (SD)] years. The mean age at diagnosis was 74.8 (±12.7 SD) years, and 1469 (45.5%) were female. HFpEF was the largest cohort (46.6%, npEF = 1505), HFmrEF constituted 16.1% (nmrEF = 520), and HFrEF 18.5% (nrEF = 596) of the population, while 18.8% (nu = 606) of patients remained unassigned due to insufficient evidence to support categorization. At baseline, measurement of natriuretic peptide (NP; brain NP and N‐terminal pro‐B‐type NP) and echocardiographic report data were available for 592 (18.3%) and 2621 (81.2%) patients, respectively. A total of 2099 (65.0%) of the HF cohort had access to a cardiology‐led outpatient clinic prior to the HF diagnosis, and 602 (18.7%) attended cardiac rehabilitation post‐diagnosis. The 5 year crude survival rate was 37.8% [95% confidence interval (CI) (35.2–40.7%)], 42.3% [95% CI (38.0–47.2%)], and 45.5% [95% CI (41.0–50.4%)] for HFpEF, HFrEF, and HFmrEF, respectively. Conclusions Low survival rates were observed across all HF groups, along with suboptimal rates of NP testing and specialist assessments. These findings suggest missed opportunities for timely and accurate HF diagnosis, a pivotal first step in improving outcomes for HF patients. Addressing these gaps in diagnosis and management is urgently needed.

Abstract High altitude (HA) ascent imposes systemic hypoxia and associated risk of acute mountain sickness. Acute hypoxia elicits a hypoxic ventilatory response (HVR), which is augmented with chronic HA exposure (i.e., ventilatory acclimatization; VA). However, laboratory‐based HVR tests lack portability and feasibility in field studies. As an alternative, we aimed to characterize area under the curve (AUC) calculations on Fenn diagrams, modified by plotting portable measurements of end‐tidal carbon dioxide (PETCO2) against peripheral oxygen saturation (SpO2) to characterize and quantify VA during incremental ascent to HA (n = 46). Secondarily, these participants were compared with a separate group following the identical ascent profile whilst self‐administering a prophylactic oral dose of acetazolamide (Az; 125 mg BID; n = 20) during ascent. First, morning PETCO2 and SpO2 measurements were collected on 46 acetazolamide‐free (NAz) lowland participants during an incremental ascent over 10 days to 5160 m in the Nepal Himalaya. AUC was calculated from individually constructed Fenn diagrams, with a trichotomized split on ranked values characterizing the smallest, medium, and largest magnitudes of AUC, representing high (n = 15), moderate (n = 16), and low (n = 15) degrees of acclimatization. After characterizing the range of response magnitudes, we further demonstrated that AUC magnitudes were significantly smaller in the Az group compared to the NAz group (P = 0.0021), suggesting improved VA. These results suggest that calculating AUC on modified Fenn diagrams has utility in assessing VA in large groups of trekkers during incremental ascent to HA, due to the associated portability and congruency with known physiology, although this novel analytical method requires further validation in controlled experiments. Highlights What is the central question of this study? What are the characteristics of a novel methodological approach to assess ventilatory acclimatization (VA) with incremental ascent to high altitude (HA)? What is the main finding and its importance? Area under the curve (AUC) magnitudes calculated from modified Fenn diagrams were significantly smaller in trekkers taking an oral prophylactic dose of acetazolamide compared to an acetazolamide‐free group, suggesting improved VA. During incremental HA ascent, quantifying AUC using modified Fenn diagrams is feasible to assess VA in large groups of trekkers with ascent, although this novel analytical method requires further validation in controlled experiments.

Abstract Objectives International guidelines recommend resection of suspected localised renal cell carcinoma (RCC), with surgical series showing benign pathology in 30%. Non‐invasive diagnostic tests to differentiate benign from malignant tumours are an unmet need. Our objective was to determine diagnostic accuracy of imaging modalities for detecting cancer in T1 renal tumours. Methods A systematic review was performed for reports of diagnostic accuracy of any imaging test compared to a reference standard of histopathology for T1 renal masses, from inception until January 2023. Twenty‐seven publications (including 2277 tumours in 2044 participants) were included in the systematic review, and nine in the meta‐analysis. Results Forest plots of sensitivity and specificity were produced for CT (seven records, 1118 participants), contrast‐enhanced ultrasound (seven records, 197 participants), [99mTc]Tc‐sestamibi SPECT/CT (five records, 263 participants), MRI (three records, 220 participants), [18F]FDG PET (four records, 43 participants), [68Ga]Ga‐PSMA‐11 PET (one record, 27 participants) and [111In]In‐girentuximab SPECT/CT (one record, eight participants). Meta‐analysis returned summary estimates of sensitivity and specificity for [99mTc]Tc‐sestamibi SPECT/CT of 88.6% (95% CI 82.7%–92.6%) and 77.0% (95% CI 63.0%–86.9%) and for [18F]FDG PET 53.5% (95% CI 1.6%–98.8%) and 62.5% (95% CI 14.0%–94.5%), respectively. A comparison hierarchical summary receiver operating characteristic (HSROC) model did not converge. Meta‐analysis was not performed for other imaging due to different thresholds for test positivity. Conclusion The optimal imaging strategy for T1 renal masses is not clear. [99mTc]Tc‐sestamibi SPECT/CT is an emerging tool, but further studies are required to inform its role in clinical practice. The field would benefit from standardisation of diagnostic thresholds for CT, MRI and contrast‐enhanced ultrasound to facilitate future meta‐analyses.

Abstract Objectives The observational ‘Feeling Hot’ study aims to evaluate the feasibility of employing overnight penile temperature measurements for the detection of nocturnal erections, thereby contributing to the advancement and modernization of a non‐invasive diagnostic system for erectile dysfunction. Subjects/Patients and Methods In this proof‐of‐concept study, 10 healthy men aged 20–25 were recruited, following the methodology outlined in the ‘Staying Hot’ study by Torenvlied et al. Participants underwent ambulatory overnight penile temperature measurements concurrent with RigiScan recordings. Key outcome measures included baseline and peak penile temperatures during RigiScan‐annotated nocturnal erections. Reference measurements of the thigh temperature were also taken to assess nocturnal temperature variations. Results Statistically significant penile temperature increases (p = 0.008, n = 9) were observed during nocturnal erections, with an average elevation of 1.47°C noted during the initial erections. This underscores the practical utility of penile temperature measurements in detecting erection onset. Challenges arose in accurately determining erection duration and subsequent erection onsets due to the persistence of elevated temperatures following initial erections, termed the ‘Staying Hot effect’. Reference thigh temperature measurements aided in addressing this challenge. Conclusion Examining overnight penile temperature alongside simultaneous RigiScan recordings has yielded valuable insights into the viability of using the temperature methodology for detecting nocturnal erections. The ‘Feeling Hot’ study findings demonstrate significant penile temperature elevation during nocturnal erections in healthy young men, highlighting the potential of integrating this measurement methodology into the design of a modernized tool for ambulatory erectile dysfunction diagnostics. Further development of an advanced sensor system to comprehensively assess erection duration and quality is essential for enhancing clinical applicability.

Abstract Background The information relating to the outcome specifically for juvenile dogs with meningoencephalitis of unknown etiology (MUE) is lacking. Objectives To describe the clinical presentation, diagnostic findings, treatment, and outcome in a cohort of dogs with MUE

Abstract Purpose/Objective This study examined (a) differences in demographic and injury‐related characteristics following traumatic brain injury (TBI) between Native American and White individuals; (b) differences in community participation between Native American and White individuals with TBI at 1, 2, and 5 years after TBI; and (c) whether demographic or injury‐related characteristics account for community participation disparities. Research Method/Design A sample of 63 Native American individuals demographically matched to 63 White individuals (n = 126) was enrolled while on acute rehabilitation for moderate or severe TBI. Baseline demographic and injury‐related characteristics were collected at this time and the Participation Assessment with Recombined Tools (PART‐O) measure of community participation at 1, 2, and 5 years after TBI. Results Native American individuals were less likely to have private insurance and be employed at the time of injury and more likely to have had lower educational attainment and engaged in binge drinking in the month prior to TBI compared to White individuals. Native American individuals demonstrated lower Out and About scores but statistically equivalent Social and Productivity scores. The difference in Out and About scores did not change as a function of time, and the overall difference between the two groups dissipated with the inclusion of statistically different sociodemographic variables. Conclusions/Implications Clinicians can provide culturally sensitive, patient‐ and family‐centered care by conducting comprehensive interviews and identifying strengths as well as risk factors that enhance or hinder community participation after TBI in Native American individuals.

ABSTRACT Climate change has marked effects on global weather patterns and oceanic systems, impacting animal behaviour and fitness in potentially profound ways. Despite this, we lack detailed information about species' responses to climatic variation. Using an 11‐year tracking dataset of over 300 individual birds, we explore the consequences of variation in the southern annular mode (SAM) and southern oscillation index (SOI) for individual behaviour and fitness in wandering albatrosses Diomedea exulans breeding in the Southern Indian Ocean. Our results reveal distinct responses between males and females to climatic variation that align with the impacts of each climatic index on the distinct foraging ranges of each sex. In positive SAM phases, linked to poorer foraging conditions in female ranges and better conditions in male ranges, females exhibited behaviour consistent with reduced foraging success: that is, fewer prey capture attempts and more movement between feeding patches. Males, on the other hand, showed no behavioural change. During positive SOI phases, associated with good foraging conditions in both male and female foraging ranges, both sexes showed evidence of more successful foraging, with birds engaging in more search behaviour, and taking shorter trips with fewer prey capture attempts, together indicating increased food intake per unit time. We found limited evidence for a role of individual variation, as measured through differences in personality, suggesting that plastic responses to climate are sufficiently important so as to obscure inter‐individual variation. Supporting this was the finding that individual breeding success was unaffected by climatic variation, suggesting that plastic foraging behaviour allows albatrosses to mitigate climate impacts and maintain reproductive output.

ABSTRACT The use of animal‐borne devices (= biologgers) has revolutionized the study of marine megafauna, yet there remains a paucity of data concerning the behavioral and physiological impacts of biologger attachment and retention. Here, we used animal‐borne cameras to characterize the behavior and dive duration of juvenile green turtles (Chelonia mydas) in The Bahamas for up to 210 min after biologger deployment (n = 58). For a “control,” we used unoccupied aerial vehicles (UAVs) to collect comparable data from nonhandled green turtles (n = 25) in the same habitats. Animal‐borne footage revealed that immediately after release turtles spent 70%–80% of their time swimming with a mean dive duration of 45.3 ± 34.3 s (SD). Over time, the percentage of time spent swimming decreased alongside an increase in dive duration until reaching a plateau around 90 min. However, the “control” UAV data for time spent swimming and dive durations were more comparable to the behaviors observed immediately after biologger deployment than during the plateau. We observed no significant differences in dive durations based on body size, and differences in behaviors based on body size were also minimal. We conclude that the effects of handling stress and biologger attachment on the behavior and dive duration of juvenile green turtles are evident up to 90 min postdeployment. After that, it is possible that either: (1) the effects of biologger deployment and retention are negligible, but UAVs may produce biased data that overestimates the proportion of time turtles typically spend swimming or (2) longer durations (> 210 min) are necessary for turtle behaviors to return to nonhandled levels and UAVs accurately represent the proportion of time turtles typically spend swimming. Answering this question, alongside further research into the physiological and behavioral implications of handling stress and biologger attachment, is essential to improve ethical biologging guidelines for sea turtles.

ABSTRACT Introduction Laparoscopic surgery (LS) has been a promising development in surgical practice globally ever since its introduction. LS has exhibited many an advantage, including bettering patient outcomes, lowering the risk of postoperative infection, and displaying economical affluence. However, its implementation in the African continent still faces various challenges. In this review, we investigated the status of laparoscopic surgery integration in Africa. Objectives In this review, we aimed to investigate the challenges posed by the implementation of LS in low resource countries as well as critically evaluating initiatives and their impact within said domiciles. We also provide recommendations that may assist in LS prosperity in these settings by focusing efforts on improving training and financial incentives. Methods A comprehensive literature review was conducted to garner up‐to‐date evidence concerning the fate of LS adoption in low‐ to middle‐income countries. This comprised the analysis of different case studies from countries including Nigeria and Botswana, and investigated relevant recommendations and policies provided by other African countries. Results Various challenges face the implementation of LS in countries with low resources comprising poor infrastructure, scarce training programs, and expert training personnel alongside financial boundaries. The adoption of LS in Africa has proved its benefits in improving patient outcomes and reducing hospital admissions. From a perspective of policy, it is crucial to sustain strong ties amongst institutions, stressing the importance of dynamic collaboration and locally tailored policies. Conclusion It has been demonstrated that LS implementations in African nations lower infection rates and expedite recovery. A strong collaboration between governments, stakeholders, and healthcare providers is fundamental for successful integration of LS. Such extension in low‐resource environments may be achieved by providing proper training programs, funding infrastructure and equipment, and fostering effective financial initiatives.

ABSTRACT Background and Aims Weight loss without adequate anabolic stimuli can lead to reductions in lean, as well as adipose, tissue. Health benefits typically associated with weight loss are therefore attenuated, as body composition potentially shifts from an obese to sarcopenic/frail phenotype. In contrast to the traditional connotation of frailty, this might occur in younger adults and is characterized by reduced performance in functional tasks of daily living. Nutritional supplements as an adjunct to weight loss intervention could support the maintenance of lean mass, particularly if structured exercise is contraindicated. This systematic review aims to quantify the effect of nutritional supplements, without concurrent exercise, on lean mass in individuals undergoing pharmacological and nonpharmacological‐induced weight loss. Methods This protocol describes a prospective systematic review and meta‐analysis of randomized controlled trials investigating the effect of nutritional supplements on lean mass during weight loss. Comparison arms will not use nutritional supplements. Literature searches will be conducted using the following online databases: Embase, MEDLINE, Web of Science, Google Scholar, and OpenGrey. Outcome measures related to body composition, lean mass, skeletal muscle mass/size, or physical function will be extracted. Risk of bias will be assessed using the United States National Heart Lung and Blood Institute quality assessment tool for controlled intervention studies. A meta‐analysis will be conducted to synthesize comparable outcomes. Results The results of this review will be reported in adherence to PRISMA (Preferred Reporting Items for Systematic Review and Meta‐Analysis Protocols) standards, and published in a peer‐reviewed journal. Conclusion This study will be the first to systematically review nutritional interventions for the preservation or accretion of lean mass during weight loss. This review will identify gaps in the literature and inform the development of optimized weight loss strategies, for use in research and practice. Trial Registration International Prospective Register of Systematic Reviews: PROSPERO CRD42024521540.

ABSTRACT Background Psychotropic medications are a common treatment modality for people living with severe and persistent mental illness (SPMI). While effective in reducing relapse and hospitalisation, psychotropic medications cause numerous side effects, varying in nature and severity. Identification and management of side effects is crucial in the ongoing management of SPMI. Objective To characterise the side effects of psychotropic medications, experienced by a sample of consumers living with SPMI, using a validated tool. Setting and Participants Consumers with SPMI living in the community were recruited from all 25 community pharmacies across four Australian regions, which were allocated to the intervention arm of the Bridging the Gap between Physical and Mental Illness (PharMIbridge) randomised controlled trial (RCT). Main Outcome Measures Responses to the My Medicines & Me Questionnaire (M3Q). Results Consumers (n = 156) most frequently reported side effects in the categories of sleep‐related side effects (80.8%, n = 126), mood‐related side effects (75.6%, n = 118) and weight and appetite changes (60.3%, n = 107). Daytime somnolence was the most reported individual side effect (68.6%, n = 107). Mood‐related side effects were ranked as the most bothersome, followed by sleep‐related side effects and weight and appetite changes. More than one‐quarter (29.5%, n = 46) of consumers reported choosing not to take their medications due to side effects. Consumers more frequently told family and friends about the side effects rather than healthcare professionals. Conclusions An overwhelming majority of consumers experienced at least one side effect attributed to their psychotropic medication, with many experiencing multiple. These findings highlight the critical need to regularly engage with consumers to discuss, identify and manage side effects to treatment burden, reduce risk of non‐adherence and improve their treatment experience. Patient or Public Contribution The PharMIbridge RCT included a training programme and intervention service that was co‐designed and co‐delivered with people with lived experience of mental illness. The research team, expert advisory panel and mentors who supported the delivery and implementation of the training and intervention included participants who have lived experience of mental illness or caring for someone with mental illness. Trial Registration ANZCTR12620000577910.

ABSTRACT Objective For people with type 2 diabetes who are overweight, weight loss increases the likelihood of achieving diabetes remission. The aim here was to draw on the experiences of people living with type 2 diabetes and coaches who deliver type 2 diabetes prevention and remission programmes. This was done to develop a service that increases the proportion of people who achieve remission by identifying an effective weight management service. Research Design and Methods A qualitative researcher and co‐researcher with type 2 diabetes conducted 37 narrative interviews with adults with type 2 diabetes (October 2022–June 2023) and 16 semi‐structured interviews with health coaches delivering type 2 diabetes programmes in England. Data were analysed using Reflexive Thematic Analysis. Participants were diverse in ethnicity, socioeconomic status, age, gender and years since diabetes diagnosis. Results Four themes were generated relating to moments in a person's diabetes care: (1) coming to terms with diagnosis, (2) lightbulb moments, (3) sustaining change as normal and (4) becoming expert/building confidence. These four themes were united under a high‐level interpretivist theme: ‘Same journey, different experience’, capturing the mismatch between a linear rigid care pathway described by coaches and the diversity of experience of people living with type 2 diabetes. Conclusions Coaches and people with type 2 diabetes are aligned on their reports of key moments in adapting to diabetes. Participants’ desire for flexibility in their care contrasted with coach reports of rigid service provision. These insights may enable more people with type 2 diabetes to engage and adhere to weight management services aimed at diabetes remission.

Abstract Spontaneous pneumomediastinum is an infrequent condition typically secondary to smoking, illicit drug use, or asthma. The condition often follows barotrauma or bronchial hyperactivity, causing alveolar destruction and air trapping within the mediastinum. Rarely, it may present following strenuous exercise, particularly in tall, thin males, resembling the presentation of pneumothorax. In this case, a 23‐year‐old male with no prior medical history presented to the emergency department with chest pain and dyspnea following intense training for a triathlon. Following a normal chest x‐ray, a high‐resolution computed tomography imaging revealed the presence of spontaneous pneumomediastinum. The patient was admitted for observation and managed conservatively with close monitoring for potential complications such as pneumothorax or pneumopericardium. Emergency physicians should maintain a high index of suspicion for spontaneous pneumomediastinum in patients presenting with acute chest pain and dyspnea, especially in the absence of significant comorbidities. This condition can mimic other cardiopulmonary emergencies, necessitating its inclusion in the differential diagnosis to ensure accurate and timely management.

Background Cardiovascular disease (CVD) remains a leading cause of death for women in the United States, with veterans being at potentially higher risk than their nonveteran counterparts due to accelerated aging and distinct biopsychosocial mechanisms. We examined pathways between selected indicators of socioeconomic status (SES) such as education, occupation, household income, and neighborhood SES and major CVD events through lifestyle and health characteristics among veteran and nonveteran postmenopausal women. Methods and Results A total of 121 286 study‐eligible WHI (Women's Health Initiative) participants (3091 veterans and 118 195 nonveterans) were prospectively followed for an average of 17 years, during which 16 108 major CVD events were documented. Using generalized structural equations modeling coupled with survival analysis techniques, we estimated the effects of SES on major CVD events through smoking, body mass index, comorbidities, cardiometabolic risk factors, and self‐rated health, controlling for WHI component, region, age, race, ethnicity, marital status, and health care provider access. Among veterans, SES characteristics were indirectly related to major CVD events through body mass index, comorbidities, cardiometabolic risk factors, and self‐rated health. Among nonveterans, lower education (β= 0.2, P

Abstract This strategic plan summarizes the major accomplishments achieved in the last quinquennial by the soybean [Glycine max (L.) Merr.] genetics and genomics research community and outlines key priorities for the next 5 years (2024–2028). This work is the result of deliberations among over 50 soybean researchers during a 2‐day workshop in St Louis, MO, USA, at the end of 2022. The plan is divided into seven traditional areas/disciplines: Breeding, Biotic Interactions, Physiology and Abiotic Stress, Functional Genomics, Biotechnology, Genomic Resources and Datasets, and Computational Resources. One additional section was added, Training the Next Generation of Soybean Researchers, when it was identified as a pressing issue during the workshop. This installment of the soybean genomics strategic plan provides a snapshot of recent progress while looking at future goals that will improve resources and enable innovation among the community of basic and applied soybean researchers. We hope that this work will inform our community and increase support for soybean research.

ABSTRACT Estuarine habitats serve as critical feeding and nursery grounds for many aquatic species and support fisheries. However, monitoring these complex ecosystems using conventional trawling methods is destructive, costly, and labor‐intensive. This study compared trawling and a multi‐marker environmental DNA (eDNA) metabarcoding approach to monitor marine vertebrate and crustacean communities in an estuarine environment in subtropical Hong Kong. We analyzed 16 bottom trawl samples and the eDNA from 32 two‐liter water samples using primer sets specific to fishes and mammals (MiFish‐U, 12S‐V5, and Berry‐Fish) and decapod crustaceans (MiDeca). We found that the eDNA approach detected more pelagic and demersal fishes (237 vs. 106 in trawling) and elasmobranchs (6 vs. 3) than trawling. The eDNA approach was also more effective than trawling in detecting threatened vertebrates (16 vs. 4), including the Indo‐Pacific Finless Porpoise and the critically endangered Large Yellow Croaker. Among the detected fish at species level, 70 species were detected by both approaches, 32 species were detected by trawling only, and 142 species were detected by the eDNA approach only. Regarding crustaceans, the eDNA approach detected slightly fewer decapods (61 vs. 77) and stomatopods (5 vs. 8) than trawl surveys. However, the eDNA approach could be enhanced through the development of suitable decapod‐specific primers and the expansion of the local reference database. In addition, multivariate analyses of the eDNA data revealed spatial patterns of fish and crustacean assemblages that might be associated with sediment loading, oxygen, and nutrient levels. Furthermore, there was a positive correlation between eDNA read counts and trawl catch, but their correlation coefficient was low. We conclude that eDNA metabarcoding can provide high‐resolution detection of species, composition, and unravel community–environment relationships in estuarine ecosystems. Overall, integrating the non‐destructive eDNA approach can complement the conventional trawling method for better‐informed sustainable fishery management and conservation.

Abstract To fulfill their conservation potential and provide safeguards for biodiversity, marine protected areas (MPAs) need coordinated research and monitoring for informed management through effective evaluation of ecosystem dynamics. However, coordination is challenging, often due to knowledge gaps caused by inadequate access to data and resources, compounded by insufficient communication between scientists and managers. We propose to use the world's largest MPA in the Ross Sea, Antarctica as a model system to create a comprehensive framework for an interdisciplinary network supporting research and monitoring that could be implemented in other remote large‐scale international MPAs. Our proposed framework has three key components: (i) policy engagement, including delineation of policy needs and ecosystem metrics to assess MPA effectiveness; (ii) community partner engagement to elevate diverse voices, build trust, and share resources; and (iii) integrated science comprising three themes. These themes are: advancement of data science and cyberinfrastructure to facilitate data synthesis and sharing; biophysical modeling towards understanding ecosystem changes and uncertainties; and execution of observational and process studies to address uncertainties and evaluate ecosystem metrics. This proposed framework can improve MPA implementation by generating policy‐relevant science through this coordinated network, which can in turn improve MPA effectiveness in the Ross Sea and beyond.

Abstract Accurate estimates of mutation rates derived from genome‐wide mutation accumulation (MA) data are fundamental to understanding basic evolutionary processes. The rapidly improving high‐throughput sequencing technologies provide unprecedented opportunities to identify single nucleotide mutations across genomes. However, such MA derived data are often difficult to analyze and the performance of the available methods of analysis is not well understood. In this study, we used the existing Bayesian Genotype Caller adapted for MA data that we refer to as Bayesian Mutation Finder (BMF) for identifying single nucleotide mutations while considering the characteristics of the data. We compared the performance of BMF with the widely used Genome Analysis Toolkit (GATK) by applying these two methods to time‐series MA data as well as simulated data. The time‐series data were obtained by propagating Daphnia pulex over an average of 188 generations and performing whole‐genome sequencing of 14 MA lines across three time points. The results indicate that BMF enables more accurate identification of single nucleotide mutations than GATK especially when applied to the empirical data. Furthermore, BMF involves the use of fewer parameters and is more computationally efficient than GATK. Both BMF and GATK found surprisingly many candidate mutations that were not confirmed at later time points. We systematically infer causes of the unconfirmed candidate mutations, introduce a framework for estimating mutation rates based on genome‐wide candidate mutations confirmed by subsequent sequencing, and provide an improved mutation rate estimate for D. pulex.

ABSTRACT Juvenile growth rate is a critical demographic parameter, as it shortens the time to maturity and often dictates how long individuals remain vulnerable to predation. However, developing a mechanistic understanding of the factors determining growth rates can be difficult for wild populations. The gopher tortoise (Gopherus polyphemus) is an ecosystem engineer threatened by habitat loss and deficient management of pinelands in the southeastern United States. We investigated the factors governing immature gopher tortoise growth and explored the use of drone‐based imagery for habitat assessment by comparing predictive models based on ground‐based plant surveys versus drone‐derived data. From 2021 to 2022, we tracked and measured immature tortoises in native sandhill and human‐modified, ruderal habitat in south‐central Florida. Using quarterly, high‐resolution drone imagery, we quantified plant cover types and vegetation indices at each occupied burrow and measured the frequency of occurrence of forage species by hand. Annual growth rates of immature tortoises in ruderal habitat were higher than those in sandhill and were the highest published for this species. Models based on drone‐derived data were able to explain similar proportions of variation in growth as ground‐collected measures of forage, especially during the late dry season when both types of models were most predictive. Habitat differences in forage nitrogen content were also more pronounced during this season, when dominant ground cover in ruderal habitat (bahiagrass) had much higher nitrogen content than dominant ground cover in sandhill (wiregrass). Despite concerns about potential growth‐survival trade‐offs, tortoises in ruderal habitat did not exhibit lower apparent survival. Our findings indicate that habitat dominated by nutritious non‐native grass can provide a valuable supplement to native sandhill through the mechanism of increased growth rates due to higher forage quality. Finally, our study demonstrates that drone technology may facilitate management by providing less labor‐intensive ways to assess habitat quality for this and other imperiled herbivores.

Abstract Screening a transposon‐mutagenized soybean population led to the discovery of a recessively inherited chlorotic phenotype. This “y24” phenotype results in smaller stature, weaker stems, and a smaller root system. Genome sequencing identified 15 candidate genes with mutations likely to result in a loss of function. Amplicon sequencing of a segregating population was then used to narrow the list to a single candidate mutation, a single‐base change in Glyma.07G102300 that disrupts splicing of the second intron. Single cell transcriptomic profiling indicates that this gene is expressed primarily in mesophyll cells, and RNA sequencing data indicate that it is upregulated in germinating seedlings by cold stress. Previous studies have shown that mutations to Os05g34040, the rice ortholog of Glyma.07G102300, produced a chlorotic phenotype that was more pronounced in cool temperatures. Growing soybean y24 mutants at lower temperatures also resulted in a more severe phenotype. In addition, transgenic expression of wild‐type Glyma.07G102300 in the knockout mutant of the Arabidopsis ortholog At4930720 rescues the chlorotic phenotype, further supporting the hypothesis that the mutation in Glyma.07G102300 is causal of the y24 phenotype. The variant analysis strategy used to identify the genes underlying this phenotype provides a template for the study of other soybean mutants.

Abstract Binder jet additive manufacturing is well suited for fabricating large (order of cm) and geometrically complex ceramic preforms. However, the main challenge in producing ceramic oxide parts via binder jetting is the high‐temperature postprocess tasked with eliminating internal porosity to achieve full densities. In this work, we demonstrate the ability to produce oxide ceramic parts with desirable densities by sintering binder jetted preforms. We investigate the sintering behavior of binder jetted preforms composed of three oxide powders with distinct morphologies: ball‐milled alumina, gas‐atomized silica, and sintered‐agglomerated zirconia. We fabricate the preform samples using a commercial binder jetting system and a conventional die‐pressing technique to understand the effect of starting densities. Furthermore, we parametrize the heating profiles to understand the effect of sintering temperature, sintering duration, and heating rate on each powder's densification behavior, microstructure, and phase composition. Results show the relatively low starting densities within the binder jetted preforms caused the onset sintering temperature to be higher than what is documented in conventional sintering studies. As expected, we observed sintered densities increase with respect to sintering temperature and duration. These findings were utilized to downselect sintering parameters capable of achieving high densities (>96%). Herein, this study validates the sintering of binder jetted preforms as a suitable way to manufacture ceramic parts, regardless of powder morphologies, thereby increasing the robustness of the supply chain involved in additive manufacturing of ceramic oxides.

Background White matter hyperintensities (WMH) and their progression are associated with risk of dementia and stroke, so are an important target for clinical trials. The cost of broad magnetic resonance imaging (MRI) screening to identify eligible individuals, however, limits the feasibility of designing clinical trials targeting WMH. A low‐cost retinal or clinical screening measure before MRI could reduce recruitment costs versus an MRI‐only screening design in a hypothetical clinical trial. Methods and Results Data from the Atherosclerosis Risk in Communities study with valid retinal and WMH measurements (N=1311) were used. To identify a population at greater likelihood of significant WMH on MRI and thus reduce the number of screening MRIs required, we evaluated 3 theoretical prescreening measures: (1) retinal, (2) clinical, (3) combined clinical‐retinal. Given a target sample for clinical trials (N=646), we calculated screening sample sizes based on the proportion within the population having an elevated score for each prescreening measure (separately) multiplied by the proportion of significant WMH among those with that prescreening feature. Recruitment costs were calculated using estimated retinal and MRI cost estimates. Compared with the estimated cost of MRI‐only screening (>$4.24 million, requiring MRI on 6526 participants), prescreening for a high clinical score resulted in total cost of $2.47 million, with an initial screening group of 52 778 participants, with MRI in 3801. A high clinical‐retinal score cutoff resulted in costs of $2.9 million while requiring 13 572 participants, with 3801 completing MRI. Conclusions A 2‐stage design with low‐cost prescreening measures is a promising approach, resulting in reduced theoretical recruitment costs compared with an MRI‐only design.

Abstract The newly proposed revised criteria for diagnosis and staging of Alzheimer's disease (AD) by the Alzheimer's Association (AA) Workgroup represent a significant milestone in the field. These criteria offer objective measures for diagnosing and staging biological AD, bridging the gap between research and clinical care. Although implementation feasibility may vary across regions and settings, improving the availability and accuracy of biomarkers, especially plasma biomarkers, is expected to enhance the applicability of these criteria in clinical practice. The Fall 2023 Alzheimer's Association Research Roundtable (AARR) meeting served as a forum for gathering industry perspectives and feedback on these revised criteria, ensuring that the new criteria inform research, clinical trial design, and clinical care. In this article, we outline a summary of the newly proposed “Revised Criteria for Diagnosis and Staging of AD: AA Workgroup” and provide highlights from the AARR meeting in fall 2023. Highlights The Alzheimer's Association Research Roundtable (AARR) convened leaders from industry, academia, and government, to review the Revised Criteria for Diagnosis and Staging of AD: AA Workgroup, and gather industry perspectives and feedback on these revised criteria before its publication. The newly proposed revised criteria for diagnosis and staging of Alzheimer's disease (AD) by the AA's Workgroup represent a significant milestone, offering objective measures for the biological and staging of AD and bridging the gap between research and clinical care. Improving the availability and accuracy of biomarkers, especially blood‐based biomarkers (BBMs) is expected to improve clinical research and enhance the applicability of these criteria in clinical practice.

Abstract We sought to determine the repeatability of EFL in healthy adults during incremental cycle exercise. We hypothesized that the repeatability of EFL would be “strong” when assessed as a binary variable (i.e., absent or present) but “poor” when assessed as a continuous variable (i.e., % tidal volume overlap). Thirty‐two healthy adults performed spirometry and an incremental cycle exercise test to exhaustion on two occasions. Standard cardiorespiratory variables were measured at rest and throughout exercise, and EFL was assessed by overlaying tidal expiratory flow‐volume and maximal expiratory flow‐volume curves. The repeatability of EFL was determined using Cohen's κ for binary assessments of EFL and intraclass correlation (ICC) for continuous measures of EFL. During exercise, n = 12 participants (38%) experienced EFL. At peak exercise, the repeatability of EFL was “minimal” (κ = 0.337, p = 0.145) when assessed as a binary variable and “poor” when measured as a continuous variable (ICC = 0.338, p = 0.025). At matched levels of minute ventilation during high‐intensity exercise (i.e., >75% of peak oxygen uptake), the repeatability of EFL was “weak” when measured as a binary variable (κ = 0.474, p = 0.001) and “moderate” when measured as a continuous variable (ICC = 0.603, p

Abstract Objective Learning Health Systems (LHSs) have not directly informed evidence‐based policymaking. The Translation‐to‐Policy (T2P) Learning Cycle aligns scientists, end‐users, and policymakers to support a repeatable roadmap of innovation and quality improvement to optimize effective policies toward a common public health goal. We describe T2P learning cycle components and provide examples of their application. Methods The T2P Learning Cycle is based on the U.S. Department of Veterans Affairs (VA) Office of Research and Development and Quality Enhancement Research Initiative (QUERI), which supports research and quality improvement addressing national public health priorities to inform policy and ensure programs are evidence‐based and work for end‐users. Incorporating LHS infrastructure, the T2P Learning Cycle is responsive to the Foundations for Evidence‐based Policymaking Act, which requires U.S. government agencies to justify budgets using evidence. Results The learning community (patients, providers, clinical/policy leaders, and investigators) drives the T2P Learning Cycle, working toward one or more specific, shared priority goals, and supports a repeatable cycle of evidence‐building and evaluation. Core T2P Learning Cycle functions observed in the examples from housing/economic security, precision oncology, and aging include governance and standard operating procedures to promote effective priority‐setting; complementary research and quality improvement initiatives, which inform ongoing data curation at the learning system level; and sustainment of continuous improvement and evidence‐based policymaking. Conclusions The T2P Learning Cycle integrates research translation with evidence‐based policymaking, ensuring that scientific innovations address public health priorities and serve end‐users through a repeatable process of research and quality improvement that ensures policies are scientifically based, effective, and sustainable.

Abstract Most organic carbon delivered to the seafloor is degraded within the bioturbated layer. Theory and empirical evidence have shown that organic carbon reactivity relates to the age of a particle. However, due to particle mixing, the age‐depth linear relation induced by sediment accretion is obfuscated. Here we combine a Lagrangian particle tracking model that resolves the age distribution of particles in the bioturbated zone and couple it to age‐dependent organic carbon degradation. Depth profiles for organic carbon concentration, reactivity and degradation rate are presented for sediments receiving low and high reactivity organic carbon in coastal, continental slope and deep‐sea environments. Our results show that a simple first‐order kinetics model suffices for well‐mixed sediments and systems receiving pre‐processed materials. A reactive continuum approach is needed for poorly mixed sediments receiving highly reactive organic carbon and for sediments below the bioturbated layer.

ABSTRACT Introduction The term “Mediterranean lifestyle” has gained increasing prominence in recent years, yet a specific definition remains elusive. In response, the Mediterranean Lifestyle Medicine Institute Board of Directors convened a multidisciplinary panel comprising international experts and leaders in lifestyle medicine. Their goal was to review existing literature and formulate a consensus definition of the “traditional Mediterranean lifestyle (tMedL),” referring to the historical way of living of the people in the Mediterranean region. This paper presents the agreed consensus statement and a comprehensive holistic definition of the term “traditional Mediterranean lifestyle.” Methods Major medical and social sciences electronic databases from inception to February 2023 were searched, employing keywords relevant to the Mediterranean lifestyle and its constituent elements (diet, physical activity, sleep, stress, socialization). Subsequently, definitions for each pillar were created and synthesized to derive a comprehensive definition of the “traditional Mediterranean lifestyle.” Results This proposed definition received ratification from the Mediterranean Lifestyle Medicine Institute's expert working group during the First International Mediterranean Lifestyle Medicine Conference held in June 2023 on the island of Leros, Greece. “The traditional Mediterranean lifestyle is characterized by its diverse and adaptable nature. Key facets encompass conviviality, lifelong social connectedness, purposeful living, strong community and familial bonds, harmony with nature and the environment, profound spirituality, adherence to religious practices, preservation of local customs, resilience cultivated through adversity, and a commitment to moderation across all spheres of life.” Conclusions This definition comprehensively outlines the primary lifestyle factors ingrained in Mediterranean inhabitants across generations. Its holistic nature furnishes a crucial conceptual framework for directing lifestyle medicine practitioners in assisting patients to mitigate diseases, promote overall well‐being, devise research initiatives to investigate the health ramifications of this lifestyle, and inform curriculum development.

Abstract Extracellular vesicles (EVs) mediate intercellular communication in many physiologic processes and can modulate immune responses in individuals with cancer. Most studies of EVs in cancer have focused on their tumour promoting properties. Whether and how EVs might mediate tumour regression besides carrying antigens has not been well characterized. Using a mouse model of highly immunogenic regressor versus poorly immunogenic progressor tumour cells, we have characterized the role of EVs in activating macrophages and promoting tumour rejection. We found that the signalling molecule MAP2K1 (MEK1) is enriched in EVs secreted by regressor relative to progressor cells. Progressor EVs engineered to have levels of MEK1 similar to regressor EVs could inhibit tumour growth by indirectly promoting adaptive immunity in both syngeneic and 3rd party tumours. This effect required MEK1 activity and could occur by activating macrophages to promote adaptive immune responses against the tumour via the cytokine interferon‐gamma. Our results suggest that MEK inhibition may be deleterious to cancer treatment, since MEK1 plays an important cell‐extrinsic, tumour‐suppressive role within EVs. Moreover, the delivery of MEK1 to tumour‐associated macrophages, either by EVs, nanoparticles, or some other means, could be a useful strategy to treat cancer via the activation of anti‐tumour immunity.

Abstract A causal mechanism for the Volgian Isotopic Carbon Excursion (VOICE) remains enigmatic. Elemental geochemical profiles of the Deer Bay Formation, Sverdrup Basin, Arctic Canada that record the VOICE and contemporaneous strata are herein examined to provide insight into depositional environments during Late Jurassic‐Early Cretaceous time. Silver (Ag) and Cadmium (Cd) are enriched across the VOICE at localities on Axel Heiberg Island, and in Tithonian (∼Volgian) strata of Ellef Ringnes Island. Other redox‐sensitive trace elements do not exhibit spatially or temporally consistent patterns and indicate oxic conditions. A lack of relationship across the VOICE between Ag and the quality, quantity, and isotopic composition of organic matter suggests that the negative isotope excursion and interval of Ag enrichment are not merely functions of changes in organic matter source or amount, while a lack of spatially consistent change in geochemical indices of weathering similarly excludes climate change and/or sediment provenance as a driver. Therefore, in a ventilated setting and without marked changes in organic matter content, Ag enrichment may be due to hydrothermal activity. Contemporaneous Ag enrichment in strata from Svalbard suggests that a source of hot fluid sufficient to produce Ag‐rich seawater may have been related to rifting in the adjacent proto‐Amerasia Basin. Hydrothermal activity may also have been a widespread source of isotopically depleted carbon. This work develops new geochemical fingerprints that may be used to trace the spatial extent of hydrothermal events that do not leave an extinction pattern but may nonetheless have a far‐reaching influence on biogeochemical systems.

Abstract Existing research on the social and cultural (S&C) values of treescapes tends to be limited in scope, for example to recreation, aesthetic or health values, and much is primarily qualitative, which provides rich detail but does not lend itself easily to incorporation into decision‐making. Having a way to quantify the range of S&C values associated with treescapes is important if decision‐makers are to effectively take these into account. This issue is particularly important currently with ambitious plans to increase tree cover alongside growing threats to treescapes from climate change and tree pests and diseases. This paper outlines the development of a new composite measure to quantify the S&C values associated with treescapes. The development of the measure resulted in a set of 19 statements across six categories of S&C value. We present results from using the measure in a survey with a representative sample of 5000 people across England together with the results of a factor analysis, which suggests a way to simplify the measure into five statements. We examine the measure through the lens of relational values and suggest that a majority of the values in our measure are relational. Policy implications. The composite measure can be used by decision‐makers looking to develop their evidence base regarding the value of treescapes in their area, or for exploring the impact of tree pests and diseases. It has already been used by more than one local authority in England. While data collection was limited to England, we suggest that the measure is applicable across a wider range of countries. Read the free Plain Language Summary for this article on the Journal blog.

Abstract Increasing placental perfusion (PP) could improve outcomes of growth‐restricted fetuses. One way of increasing PP may be by using phosphodiesterase (PDE)‐5 inhibitors, which induce vasodilatation of vascular beds. We used a combination of clinically relevant magnetic resonance imaging (MRI) techniques to characterize the impact that tadalafil infusion has on maternal, placental and fetal circulations. At 116–117 days’ gestational age (dGA; term, 150 days), pregnant ewes (n = 6) underwent fetal catheterization surgery. At 120–123 dGA ewes were anaesthetized and MRI scans were performed during three acquisition windows: a basal state and then ∼15–75 min (TAD 1) and ∼75–135 min (TAD 2) post maternal administration (24 mg; intravenous bolus) of tadalafil. Phase contrast MRI and T2 oximetry were used to measure blood flow and oxygen delivery. Placental diffusion and PP were assessed using the Diffusion‐Relaxation Combined Imaging for Detailed Placental Evaluation—‘DECIDE’ technique. Uterine artery (UtA) blood flow when normalized to maternal left ventricular cardiac output (LVCO) was reduced in both TAD periods. DECIDE imaging found no impact of tadalafil on placental diffusivity or fetoplacental blood volume fraction. Maternal‐placental blood volume fraction was increased in the TAD 2 period. Fetal DO2 and V̇O2 were not affected by maternal tadalafil administration. Maternal tadalafil administration did not increase UtA blood flow and thus may not be an effective vasodilator at the level of the UtAs. The increased maternal–placental blood volume fraction may indicate local vasodilatation of the maternal intervillous space, which may have compensated for the reduced proportion of UtA DO2.