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Abstract Background: Mesenchymal stem cells (MSCs) derived from gestational tissues offer a promising avenue for prenatal intervention in congenital malformations although their application is hampered by concerns related to cellular plasticity and the need for invasive, high-risk surgical procedures. Here, we present naturally occurring exosomes (EXOs) isolated from amniotic fluid-derived MSCs (AF-MSCs) and their mimetic analogs (MIMs) as viable, reproducible, and stable alternatives. These nanovesicles present a minimally invasive therapeutic option, addressing the limitations of MSC-based treatments while retaining therapeutic efficacy. Methods: MIMs were generated from AF-MSCs by combining sequential filtration steps through filter membranes with different porosity and size exclusion chromatography columns. A physicochemical, structural, and molecular comparison was conducted with exosomes (EXOs) released from the same batch of cells. Additionally, their distribution patterns in female mice were evaluated following in vivo administration, along with an assessment of their safety profile throughout gestation in a mouse strain predisposed to neural tube defects (NTDs). The possibility to exploit both formulations as mRNA-therapeutics was explored by evaluating cell uptake in two different cell types(fibroblasts, and macrophages) and mRNA functionality overtime in an in vitro experimental setting as well as in an ex vivo, whole embryo culture using pregnant C57BL6 dams. Results: Molecular and physiochemical characterization showed no differences between EXOs and MIMs, with MIMs determining a threefold greater yield. Biodistribution patterns following intraperitoneal administration were comparable between the two particle types, with the uterus being among targeted organs. No toxic effects were observed in the dams during gestation, nor were there any malformations or significant differences in the number of viable versus dead fetuses detected. MIMs delivered a more intense and prolonged expression of mRNA encoding for green fluorescent protein in macrophages and fibroblasts. An ex-vivo whole embryo culture demonstrated that MIMs mainly accumulate at the level of the yolk sac, while EXOs reach the embryo. Conclusions: The present data confirms the potential application of EXOs and MIMs as suitable tools for prevention and treatment of NTDs and proposes MIMs as prospective vehicles to prevent congenital malformations caused by in utero exposure to drugs.

Cucurbita species (pumpkin, squash or gourd) are native to North America and are cultivated for several thousand years. They are used as food and feed, but also in personal care, folk medicine as anthelmintic, art and festivals such as Halloween. This review focuses on the dehydration and drying of the pulp of edible pumpkin such as C. moschata, C. maxima, or C. pepo. Dehydration processes refer to water removal by hot air or heated surfaces, while drying processes are more general. In this review, the state-of-the-art related to the methods and techniques of pumpkin dehydration and drying was revealed. Among classical drying methods (sun drying, convective or forced-convective air-drying, freeze-drying, microwave drying), the recent advances on the drying techniques including osmotic, far-infrared, vacuum drying and especially combined techniques were discussed. Finally, the influence of pretreatments and drying on the quality and composition of pumpkin as well as the kinetics and models of the drying process were presented. The overview on the dehydration and drying of pumpkin allows selecting the most appropriate processing techniques for obtaining some food products or food ingredients with high shelf life and quality.

Abstract Background A prolonged first episode of psychosis (FEP) without adequate treatment is a predictor of poor clinical, functional, and health outcomes and significant economic burden. Team-based “coordinated specialty care” (CSC) for early psychosis (EP) has established effectiveness in promoting clinical and functional recovery. However, California’s CSC program implementation has been unsystematic and could benefit from standardizing its processes and data collection infrastructure. To address this, we established a consortium of EP clinics across the state via a Learning Health Care Network (LHCN) framework to develop the Early Psychosis Intervention Network of California (EPI-CAL). EPI-CAL’s LHCN developed a core battery of evidence-based measures for service users and family members and linked them together using a unique data collection and visualization application, Beehive. Methods and objectives EPI-CAL’s LHCN collects, visualizes, and aggregates data at the individual and clinic level for EP programs across California via Beehive. Beehive was designed to: (1) collect outcomes data from service users receiving care at EP programs and their support persons, (2) provide the data to providers on a secure web-based dashboard to support measurement-based care, and (3) allow data to be used for program or research analysis. We will (1) determine the feasibility of implementing an LHCN across a diverse, decentralized network of early psychosis programs, (2) determine if the implementation of an LHCN increases the delivery of measurement-based care, and (3) determine if the implementation of measurement-based care is associated with significant improvements in key service user outcomes. EPI-CAL’s network will contribute data to the Early Psychosis Intervention Network (EPINET) program. Discussion The current study aims to establish an LHCN of EP clinics in California that implements harmonized data collection using Beehive and assesses the feasibility of establishing such a network. Our goal is for this harmonized data collection approach to be used to inform decisions and develop learning opportunities for service users, staff, and administrators, and to improve outcomes for service users and their supporters in CSC care. Further, the data will enable programs and research teams to examine what elements of care lead to program success and improved treatment outcomes for service users. Clinical trials registration www.ClinicalTrials.gov , identifier NCT04007510; registered 07/05/2019.

Background: Clinically important perioperative atrial fibrillation (POAF) is a common cardiac complication after noncardiac surgery. Little is known about how patients with POAF are managed acutely and whether practices have changed over time. Methods: We conducted an observational substudy of patients who had POAF, were at elevated cardiovascular risk, and were enrolled in the PeriOperative Ischemic Evaluation (POISE)-1, 2 and 3 trials between 2002 and 2021. POAF was defined as new, clinically important atrial fibrillation occurring within 30 days after surgery. We assessed the use of rhythm-control and anticoagulation treatment in response to POAF, at hospital discharge and at 30 days after surgery. We assessed for temporal trends using multivariable logistic regression. Results: Of the 27,896 patients included, 545 (1.9%) developed clinically important POAF. Patients received rhythm-control treatment in 48.6% of cases. The level of use of rhythm-control treatment increased over the course of the trials (POISE-1 vs POISE-2 vs POISE-3; 40.9% vs 49.5% vs 59.1%). A later randomization date was associated independently with use of rhythm-control treatment (odds ratio, 1.05 per year; 95% confidence interval, 1.01-1.09). Anticoagulation treatment was prescribed in 21% of POAF cases. The level of anticoagulation treatement use was higher in POISE-3, compared to that in the 2 previous trials (POISE-1 vs POISE-2 vs POISE-3—16.4% vs 16.5% vs 33.6%). A later randomization date was associated independently with use of anticoagulation treatment (odds ratio, 1.06 per year; 95% confidence interval, 1.02-1.11). Conclusions: Despite the absence of randomized controlled trials, the level of use of rhythm-control and anticoagulation treatment for POAF is rising. High-quality trials are needed urgently to determine whether these interventions are safe and effective in this population. Résumé: Contexte: En chirurgie non cardiaque, la fibrillation auriculaire postopératoire (FAPO) d’importance clinique est une complication cardiaque fréquente. La prise en charge ponctuelle des patients présentant une FAPO est mal connue et on ne sait pas précisément si les pratiques ont évolué au fil du temps. Méthodologie: Nous avons mené une sous-étude d’observation auprès de patients ayant présenté une FAPO et dont le risque cardiovasculaire était élevé, et qui avaient participé aux études 1, 2 ou 3 du programme d’essais cliniques POISE (PeriOperative Ischemic Evaluation) entre 2002 et 2021. La FAPO était définie comme un nouvel épisode de fibrillation auriculaire (FA) d’importance clinique au cours des 30 jours suivant une intervention chirurgicale. Nous avons évalué l’utilisation d’un traitement visant à régulariser le rythme cardiaque et de l’anticoagulothérapie dans la prise en charge d’une FAPO, au moment du congé de l’hôpital, puis 30 jours après l’intervention chirurgicale. Nous avons procédé à l’évaluation des tendances temporelles par régression logistique multivariée. Résultats: Sur les 27 896 patients inclus dans l’analyse, 545 (1,9 %) ont présenté une FAPO d’importance clinique. Dans 48,6 % des cas, les patients ont reçu un traitement visant à régulariser le rythme cardiaque. Le taux d’utilisation d’un traitement visant à régulariser le rythme cardiaque a augmenté d’une étude à l’autre (étude POISE-1 vs étude POISE-2 vs étude POISE-3; 40,9 % vs 49,5 % vs 59,1 %, respectivement). Une date plus tardive de la répartition aléatoire était un facteur indépendant de l’utilisation d’un traitement visant à régulariser le rythme cardiaque (rapport de cotes = 1,05 par an; intervalle de confiance [IC] à 95 % : 1,01-1,09). Une anticoagulothérapie a été prescrite à 21 % des patients ayant présenté une FAPO. Le taux d’utilisation d’une anticoagulothérapie était plus élevé dans l’étude POISE-3, comparativement aux deux essais précédents (étude POISE-1 vs étude POISE-2 vs étude POISE-3; – 16,4 % vs 16,5 % vs 33,6 %, respectivement). Une date plus tardive de la répartition aléatoire était un facteur indépendant d’utilisation d’une anticoagulothérapie (rapport de cotes = 1,06 par an; IC à 95 % : 1,02-1,11). Conclusions: Malgré l’absence d’essais comparatifs avec répartition aléatoire, le taux d’utilisation d’un traitement visant à régulariser le rythme cardiaque ou d’une anticoagulothérapie chez les patients présentant une FAPO est en augmentation. Il existe un besoin urgent de réaliser des études cliniques de grande qualité afin de déterminer si ces interventions sont sûres et efficaces dans cette population de patients.

Abstract Background The Myositis Interstitial Lung Disease Nintedanib Trial (MINT) is a hybrid trial, which is enrolling patients both at local sites and remotely via a decentralised site. The trial will investigate the efficacy and safety of nintedanib in patients with progressive myositis-associated interstitial lung disease (MA-ILD). Methods/Design MINT is an exploratory, prospective randomised placebo-controlled trial. Eligible patients will have myositis and evidence of fibrosing ILD on high-resolution computed tomography (HRCT), be taking standard of care medications for myositis, and meet criteria for ILD progression within the prior 24 months based on decline in FVC, worsened fibrosis on HRCT, and/or worsened dyspnoea. Patients will be randomised 1:1 to receive nintedanib 150 mg twice daily or placebo for 12 weeks then open-label nintedanib for 12 weeks. Patients will be enrolled at local sites and a decentralised site. Most study visits will be completed remotely using telemedicine or digital health technologies. The primary endpoint is the change in Living with Pulmonary Fibrosis (L-PF) questionnaire dyspnoea domain score at week 12. Other endpoints include changes in other L-PF questionnaire domains, lung function, imaging, and physical activity, and assessment of adverse events. Data collected using remote versus clinic enrolment, and using home versus clinic spirometry, will be compared. Discussion MINT is an innovative, hybrid trial that will evaluate the effects of nintedanib on symptoms, quality of life, and ILD progression in patients with progressive MA-ILD and provide valuable information on the utility of decentralised recruitment and remote data collection in clinical trials. Trial registration Clinicaltrials.gov NCT05799755 (date of registration: 05/04/2023).

Abstract Background Regulatory applications for cell therapy face more objections compared to conventional small molecule or biological drugs, leading to delays in market approval and clinical adoption. Increased regulatory objections frequently relate to issues regarding preclinical evidence, such as experimental design of animal studies, selection of animal models, endpoints, and determination of mechanism of action. Synthesis and clarification of the preclinical evidence necessary to demonstrate treatment efficacy and advance into early-phase clinical trials is needed to help researchers avoid regulatory objections. Methods We conducted a scoping review in which we searched repositories of the International Council for Harmonisation and all national member organizations (N = 38) for documents related to preclinical studies of cell therapies. Active guidance documents related to cell therapy were included, with no restrictions based on the year or language of publication. Data extraction was conducted in duplicate with conflicts resolved through consensus discussion. Results From 1215 identified documents, a total of 182 were included and analyzed, with 71% originating from ten major regulatory agencies. The most prevalent preclinical item addressed was the mechanism of action (n = 161, 88% of documents), underscoring its importance in bridging preclinical findings to clinical application. Most documents (n = 140, 77%) emphasized the importance of using clinically relevant preclinical models, though specific recommendations on models of disease were less common (n = 81, 45%). Selection of clinically relevant intervention parameters (n = 136, 75%) and outcome measures (n = 121, 66%) were also frequently recommended, but selection of relevant comparator groups appeared less frequently (n = 35, 19%). Furthermore, robust study design elements such as randomization and blinding were less frequently recommended, appearing in 31% of documents (n = 57). Comparison with clinical trial guidance revealed a significant gap in the rigor of study design recommendations for preclinical research. Conclusions Regulatory guidance for preclinical efficacy studies often recommends a strong emphasis on the clinical relevance of animal models, intervention parameters, outcomes, and mechanism of action. Incorporating these recommendations into early preclinical studies should improve the acceptability of preclinical evidence for approval by the relevant national regulators and can be used as a guide to ensure that all evidence that regulators say they expect is efficiently assembled into new clinical trial applications.

The introduction of noble metal nanoparticles in solar cells has been proven to enhance the performance of perovskite solar cells. In this study, silver-modified photoanodes were utilized to improve the performance of perovskite solar cells through successive ionic layer adsorption and reaction (SILAR) procedures. Due to the surface plasmon resonance effect, the light trapping capacity of the device was enhanced with superior photovoltaic properties. The plasmonic effects of the introduced silver nanoparticles (AgNPs) were explored using SEM, XRD, UV-visible absorption spectrophotometer and solar simulator. The SEM results show compact morphologies and shinning surfaces indicating the presence of AgNPs. The XRD result shows a good crystal phase. The UV-vis results show enhanced optical absorption with AgNPs incorporation. The photovoltaic characteristics of the fabricated PSCs are: (i) pristine device; Jsc of 6.440 mA/cm2, Voc. of 0.948 V, FF of 0.642 and PCE of 3.917%, (ii) device with 1 SILAR of AgNPs; Jsc of 014.426 mA/cm2, Voc. of 0.949 V, FF of 0.642 and PCE of 8.795%, and (iii) device with 2 SILAR of AgNPs; Jsc of 10.815 mA/cm2, Voc of 0.917 V, FF of 0.558 and PCE of 5.536%. The device with the best performance is made of 1 SILAR cycle of AgNPs which shows an enhancement of ~2.245 times in PCE, ~2.240 times in Jsc and ~1.001 times in Voc over the reference device. The results in this study have unlocked the beneficial role of AgNPs and further contribute to understanding surface plasmon effect due to AgNPs introduction.

Abstract Background Pre-exposure prophylaxis (PrEP) to prevent HIV is severely underutilized among sexually minoritized men (SMM). Inequitable access to PrEP-prescribing facilities and providers is a critical barrier to PrEP uptake among SMM. Integrating HIV prevention services, such as PrEP screening, into pharmacy-based settings is a viable solution to addressing HIV inequities in the US. We aimed to examine willingness to obtain PrEP screening in a pharmacy and its associated correlates, leveraging Andersen’s Healthcare Utilization Model (AHUM), among a national sample of SMM in the U.S. Methods Data from the 2020 American Men’s Internet Survey, an annual online survey among SMM, were analyzed. Drawing on AHUM-related constructs, we used a modified stepwise Poisson regression with robust variance estimates to examine differences in willingness to screen for PrEP in a pharmacy. Estimated prevalence ratios (PR) were calculated with 95% confidence intervals (CI95%). Results Out of 10,816 men, most (76%) were willing to screen for PrEP in a pharmacy. Participants were more willing to screen for PrEP in a pharmacy if they (1) had a general willingness to use PrEP (PR = 1.52; CI95% =1.45, 1.59); (2) felt comfortable speaking with pharmacy staff about PrEP (PR = 2.71; CI95% =2.47, 2.98); and (3) had HIV-related concerns (PR = 1.04; CI95% =1.02, 1.06). There were no observed differences in men’s willingness to screen for PrEP in a pharmacy by race/ethnicity, education level, annual household income, nor insurance status. Conclusions Strategically offering PrEP screening in pharmacies could mitigate access-related barriers to HIV prevention services among SMM, particularly across various sociodemographic domains. Importantly, this approach has vitally important implications for addressing broader inequities in HIV prevention. Future studies should examine strategies to successfully integrate PrEP screenings in pharmacies among diverse populations, especially among those at elevated risk for HIV.

Abstract Glucagon-like peptide 1 (GLP-1) stimulates insulin secretion and holds significant pharmacological potential. Nevertheless, the regulation of energy homeostasis by centrally-produced GLP-1 remains partially understood. Preproglucagon cells, known to release GLP-1, are found in the olfactory bulb (OB). We show that activating GLP-1 receptors (GLP-1R) in the OB stimulates insulin secretion in response to oral glucose in lean and diet-induced obese male mice. This is associated with reduced noradrenaline content in the pancreas and blocked by an α2-adrenergic receptor agonist, implicating functional involvement of the sympathetic nervous system (SNS). Inhibiting GABAA receptors in the paraventricular nucleus of the hypothalamus (PVN), the control centre of the SNS, abolishes the enhancing effect on insulin secretion induced by OB GLP-1R. Therefore, OB GLP-1-dependent regulation of insulin secretion relies on a relay within the PVN. This study provides evidence that OB GLP-1 signalling engages a top-down neural mechanism to control insulin secretion via the SNS.

Abstract To promote sustainable aquaculture, the formulation of Atlantic salmon (Salmo salar) feeds has changed in recent decades, focusing on replacing standard marine-based ingredients with plant-based alternatives, increasingly demonstrating successful outcomes in terms of fish performance. However, little is known about how these plant-based diets may impact the gut microbiota at first feeding and onwards. Nutritional programming (NP) is one strategy applied for exposing fish to a plant-based (V) diet at an early stage in life to promote full utilisation of plant-based ingredients and prevent potential adverse impacts of exposure to a plant-rich diet later in life. We investigated the impact of NP on gut microbiota by introducing fish to plant ingredients (V fish) during first feeding for a brief period of two weeks (stimulus phase) and compared those to fish fed a marine-based diet (M fish). Results demonstrated that V fish not only maintained growth performance at 16 (intermediate phase) and 22 (challenge phase) weeks post first feeding (wpff) when compared to M fish but also modulated gut microbiota. PERMANOVA general effects revealed gut microbiota dissimilarity by fish group (V vs. M fish) and phases (stimulus vs. intermediate vs. challenge). However, no interaction effect of both groups and phases was demonstrated, suggesting a sustained impact of V diet (nutritional history) on fish across time points/phases. Moreover, the V diet exerted a significant cumulative modulatory effect on the Atlantic salmon gut microbiota at 16 wpff that was not demonstrated at two wpff, although both fish groups were fed the M diet at 16 wpff. The nutritional history/dietary regime is the main NP influencing factor, whereas environmental and host factors significantly impacted microbiota composition in M fish. Microbial metabolic reactions of amino acid metabolism were higher in M fish when compared to V fish at two wpff suggesting microbiota played a role in digesting the essential amino acids of M feed. The excessive mucin O-degradation revealed in V fish at two wpff was mitigated in later life stages after NP, suggesting physiological adaptability and tolerance to V diet. Future studies are required to explore more fully how the microbiota functionally contributes to the NP.

Organic farming systems are often plagued with challenges such as nutrient stress complexing with other biotic and abiotic issues. These issues can significantly affect the growth and productivity of vegetable crops, including peppers (Capsicum spp.). Grafting with suitable rootstocks is a promising technique to address these challenges and improve the growth and productivity of peppers in low-input systems. In the United States, grafting is not as commonly practiced in pepper as compared with other solanaceous and cucurbit crops, in part because of limited availability of rootstocks. This study examined promising rootstocks with demonstrated disease resistance and further explored their suitability for organic systems under normal and reduced fertilization. A hybrid Italian sweet pepper ‘Mama Mia Giallo’ was used as scion and grafted onto four different rootstocks and grown in a greenhouse in summer with natural heat stress. The plants received organic fertilizer weekly or biweekly for a period of 5 weeks. Results showed that grafting plants with the rootstocks ‘CM-334’, ‘YC-207’, ‘Keystone Resistant Giant’, and ‘Scarface’ resulted in similar or improved growth relative to nongrafted and self-grafted plants under normal and reduced fertilization. The rootstocks showed promising traits that could be explored in further stress tolerance studies. Specifically, ‘YC-207’-grafted plants showed higher nitrogen utilization efficiency, shoot nitrate content, and phosphorous content as well as higher stomatal conductance, transpiration, and electron transport rate, which is indicative of stress tolerance. ‘YC-207’-grafted plants also had lower malondialdehyde content, indicating less oxidative damage to the cell membrane. ‘CM-334’-grafted plants showed higher antioxidant activity, nitrate reductase (NR) activity, and shoot nitrate content. This study provides evidence of the value of evaluating potential rootstocks and explores grafting as a promising technique for pepper crop to improve plant growth and performance under organic systems.

Introduction Home-based, virtually-supported care models may represent the most efficient and scalable approach to delivering prehabilitation services. However, virtual approaches to prehabilitation are understudied. This manuscript describes the protocol for an internal pilot randomised controlled trial of a virtually-delivered, multimodal prehabilitation intervention.Methods and analysis We will conduct a pragmatic, individual patient, internal pilot randomised controlled trial of home-based, virtually supported, multimodal prehabilitation compared with standard perioperative care in adults undergoing elective, inpatient thoracic, abdominal, pelvic and vascular surgery at five Canadian hospitals. Participants will be partially blinded; clinicians and outcome assessors will be fully blinded. The intervention consists of 3–12 weeks of a home-based, multimodal (exercise, nutrition and psychosocial support) prehabilitation programme supported through an online platform. The primary feasibility outcomes and their progression targets are (1) monthly recruitment of>6 participants at each centre, (2) intervention adherence of>75%, (3) retention of>90% of participants at the patient-reported primary outcome point of 30-days after surgery and (4) elicitation of patient, clinician and researcher-identified barriers to our pragmatic trial. A sample size of 144 participants will be adequate to estimate recruitment, adherence and retention rates with acceptable precision. All participants will be followed to either death or up to 1 year. As an internal pilot, if no substantive changes to the trial or intervention design are required, pilot participant outcome data will migrate, unanalysed by allocation, to the future full-scale trial.Ethics and dissemination Ethical approval has been granted by Clinical Trials Ontario (Project ID: 4479) and our ethics review board (Protocol Approval #20230399–01T). Results will be disseminated through presentations at scientific conferences, peer-reviewed publications, partner organisations and engagement of social and traditional media.Trial registration number ClinicalTrials.gov identifier NCT06042491. Protocol, V.1.2, dated 6 June 2024.

COVID-19 is an infectious disease that caused a global pandemic in 2020. In the critical moments of this healthcare emergencies, the medical staff needs to take important decisions in a context of limited resources that must be carefully managed. To this end, the computer-aided diagnosis methods are extremely powerful and help them to better recognize the evidences of high-risk patients. This can be done with the support of relevant information extracted from electronic health records, lab tests and imaging studies. In this work, we present a novel fully-automatic efficient method to help the clinical decision-making process in the context of COVID-19 risk estimation, using multimodal data fusion of clinical features and deep features extracted from chest X-ray images. The risk estimation is studied in two of the most relevant and critical encountered scenarios: the risk of hospitalization and mortality. This study shows which are the most important features for each scenario, the ratio of clinical and imaging features present in the top ranking and the performance of the used machine learning models. The results demonstrate a great performance by the classifiers, estimating the risk of hospitalization with an AUC-ROC of 0.8452 ± 0.0133 and the risk of death with an AUC-ROC of 0.8285 ± 0.0210, only using a subset of the original features, and highlight the significant contribution of imaging features to hospitalization risk assessment, while clinical features become more crucial for mortality risk evaluation. Furthermore, multimodal data fusion can outperform the approaches that use one data source. Despite the model's complexity, it requires fewer features, an advantage in scenarios with limited computational resources. This streamlined, fully-automated method shows promising potential to improve the clinical decision-making process and better manage medical resources, not only in the context of COVID-19, but also in other clinical scenarios.

Abstract BackgroundThe substantial increase in smartphone ownership has led to a rise in mobile health (mHealth) app use. Developing tailored features through mHealth apps creates a pathway to address the health care needs of pediatric patients with cancer and their families who have complex care needs. However, few apps are designed specifically to integrate with pediatric cancer care. ObjectiveThis study reports a systematic search and analysis of mHealth apps available on the Apple App (iOS) and Google Play (Android) stores designed for pediatric cancer through a list of features that serve (1) patients, (2) caregivers, or (3) both audiences. MethodsFollowing PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we reviewed apps for pediatric patients with cancer and caregivers available as of January 30, 2024. We searched the Apple App and Google Play stores with a list of keyword combinations focusing on pediatric cancer care. The inclusion criteria were (1) specifically apps targeted toward pediatric patients with cancer, their families, or both; (2) available in either app store; and (3) available in English. Apps were assessed using the Mobile Application Rating Scale (MARS). The MARS is a quality assessment for mHealth apps, including components of engagement, functionality, aesthetics, and informational quality (5-point Likert scale items—1: low and 5: high quality). ResultsIn total, 22 apps were identified and 17 of those apps were available on both platforms. The most popular features (n=12) were resource sharing, symptom tracking, reminders, care team connections, journaling, community support, medication tracking, data visualizations, and appointment tracking. Features and interfaces were designed for caregivers (n=9) more frequently than the patients (n=7) while a subset of apps created options for both users (n=6). A total of 16 apps received positive reviews (mean 4.4, SD 0.59; Min=3.1, Max=5.0). A small subset (n=3) achieved over 5000 downloads; however, the majority (n=15) had fewer than 500. More than half (n=12) of the apps were not available in English. Apps requested access to a range of device functionalities to operate (mean 2.72, SD 3.13; Min=0, Max=10). Out of 22, a total of 17 apps were publicly accessible. The mean MARS scores for the apps ranged from 1.71 (SD 0.75) to 4.33 (SD 0.82). Overall, apps scored high on functionality (mean 3.72, SD 0.54) but low on engagement (mean 3.02, SD 0.93). ConclusionsOur review highlights the promising yet underdeveloped potential of mHealth apps in pediatric oncology care, underscoring the need for more inclusive, comprehensive, and integrative digital health solutions. Future developments should actively involve key stakeholders from the pediatric oncology community, including patients, families, and health care professionals, to ensure the apps meet specific needs while addressing linguistic and cultural barriers.

Abstract Microbial α-l-fucosidases catalyse the hydrolysis of terminal α-l-fucosidic linkages and can perform transglycosylation reactions. Based on sequence identity, α-l-fucosidases are classified in glycoside hydrolases (GHs) families of the carbohydrate-active enzyme database. Here we explored the sequence-function space of GH29 fucosidases. Based on sequence similarity network (SSN) analyses, 15 GH29 α-l-fucosidases were selected for functional characterisation. HPAEC-PAD and LC-FD-MS/MS analyses revealed substrate and linkage specificities for α1,2, α1,3, α1,4 and α1,6 linked fucosylated oligosaccharides and glycoconjugates, consistent with their SSN clustering. The structural basis for the substrate specificity of GH29 fucosidase from Bifidobacterium asteroides towards α1,6 linkages and FA2G2 N-glycan was determined by X-ray crystallography and STD NMR. The capacity of GH29 fucosidases to carry out transfucosylation reactions with GlcNAc and 3FN as acceptors was evaluated by TLC combined with ESI–MS and NMR. These experimental data supported the use of SSN to further explore the GH29 sequence-function space through machine-learning models. Our lightweight protein language models could accurately allocate test sequences in their respective SSN clusters and assign 34,258 non-redundant GH29 sequences into SSN clusters. It is expected that the combination of these computational approaches will be used in the future for the identification of novel GHs with desired specificities.

Abstract The telomere sequence, TTAGGG, is conserved across all vertebrates and plays an essential role in suppressing the DNA damage response by binding a set of proteins termed shelterin. Changes in the telomere sequence impair shelterin binding, initiate a DNA damage response, and are toxic to cells. Here we identify a family with a variant in the telomere template sequence of telomerase, the enzyme responsible for telomere elongation, that led to a non-canonical telomere sequence. The variant is inherited across at least one generation and one family member reports no significant medical concerns despite ~9% of their telomeres converting to the novel sequence. The variant template disrupts telomerase repeat addition processivity and decreased the binding of the telomere-binding protein POT1. Despite these disruptions, the sequence is readily incorporated into cellular chromosomes. Incorporation of a variant sequence prevents POT1-mediated inhibition of telomerase suggesting that incorporation of a variant sequence may influence telomere addition. These findings demonstrate that telomeres can tolerate substantial degeneracy while remaining functional and provide insights as to how incorporation of a non-canonical telomere sequence might alter telomere length dynamics.

Abstract The rising global energy demand necessitates innovative solutions for harnessing renewable energy sources. Solar ponds have received attention as they present a viable means to address this challenge by absorbing and storing solar radiation. This article provides a comprehensive review of solar pond technology, including its principles, applications, heat extraction mechanisms, and approaches to optimize performance, with special attention to the salt-gradient solar pond. Additionally, the article identifies challenges that currently hinder the large-scale adoption of solar pond technology and offers recommendations for future research. By providing a detailed analysis of the current trends and future research directions, this paper seeks to contribute to the ongoing efforts to improve these systems, exploring various approaches to increase their efficiency and make them more economical and environmentally sustainable.

Abstract Background Persistent pain is a common yet debilitating complication after breast cancer surgery. Given the pervasive effects of this pain disorder on the patient and healthcare system, post-mastectomy pain syndrome (PMPS) is becoming a larger population health problem, especially as the prognosis and survivorship of breast cancer increases. Interventions that prevent persistent pain after breast surgery are needed to improve the quality of life of breast cancer survivors. An intraoperative intravenous lidocaine infusion has emerged as a potential intervention to decrease the incidence of PMPS. We aim to determine the definitive effects of this intervention in patients undergoing breast cancer surgery. Methods PLAN will be a multicenter, parallel-group, blinded, 1:1 randomized, placebo-controlled trial of 1,602 patients undergoing breast cancer surgery. Adult patients scheduled for a lumpectomy or mastectomy will be randomized to receive an intravenous 2% lidocaine bolus of 1.5 mg/kg with induction of anesthesia, followed by a 2.0 mg/kg/h infusion until the end of surgery, or placebo solution (normal saline) at the same volume. The primary outcome will be the incidence of persistent pain at 3 months. Secondary outcomes include the incidence of pain and opioid consumption at 1 h, 1–3 days, and 12 months after surgery, as well as emotional, physical, and functional parameters, and cost-effectiveness. Discussion This trial aims to provide definitive evidence on an intervention that could potentially prevent persistent pain after breast cancer surgery. If this trial is successful, lidocaine infusion would be integrated as standard of care in breast cancer management. This inexpensive, widely available, and easily administered intervention has the potential to reduce pain and suffering in an already afflicted patient population, decrease the substantial costs of chronic pain management, potentially decrease opioid use, and improve the quality of life in patients. Trial registration This trial has been registered on clinicaltrials.gov (NCT04874038, Dr. James Khan. Date of registration: May 5, 2021).

Abstract Meningiomas are the most common primary intracranial tumors and can be associated with significant morbidity and mortality. Radiologists, neurosurgeons, neuro-oncologists, and radiation oncologists rely on brain MRI for diagnosis, treatment planning, and longitudinal treatment monitoring. However, automated, objective, and quantitative tools for non-invasive assessment of meningiomas on multi-sequence MR images are not available. Here we present the BraTS Pre-operative Meningioma Dataset, as the largest multi-institutional expert annotated multilabel meningioma multi-sequence MR image dataset to date. This dataset includes 1,141 multi-sequence MR images from six sites, each with four structural MRI sequences (T2-, T2/FLAIR-, pre-contrast T1-, and post-contrast T1-weighted) accompanied by expert manually refined segmentations of three distinct meningioma sub-compartments: enhancing tumor, non-enhancing tumor, and surrounding non-enhancing T2/FLAIR hyperintensity. Basic demographic data are provided including age at time of initial imaging, sex, and CNS WHO grade. The goal of releasing this dataset is to facilitate the development of automated computational methods for meningioma segmentation and expedite their incorporation into clinical practice, ultimately targeting improvement in the care of meningioma patients.

Abstract Background Pressure ulcers account for a substantial fraction of hospital-acquired pathology, with consequent morbidity and economic cost. Treatments are largely focused on preventing further injury, whereas interventions that facilitate healing remain limited. Intermittent electrical stimulation (IES) increases local blood flow and redistributes pressure from muscle-bone interfaces, thus potentially reducing ulcer progression and facilitating healing. Methods The Pressure Injury Treatment by Intermittent Electrical Stimulation (PROTECT-2) trial will be a parallel-arm multicenter randomized trial to test the hypothesis that IES combined with routine care reduces sacral and ischial pressure injury over time compared to routine care alone. We plan to enroll 548 patients across various centers. Hospitalized patients with stage 1 or stage 2 sacral or ischial pressure injuries will be randomized to IES and routine care or routine care alone. Wound stage will be followed until death, discharge, or the development of an exclusion criteria for up to 3 months. The primary endpoint will be pressure injury score measured over time. Discussion Sacral and ischial pressure injuries present a burden to hospitalized patients with both clinical and economic consequences. The PROTECT-2 trial will evaluate whether IES is an effective intervention and thus reduces progression of stage 1 and stage 2 sacral and ischial pressure injuries. Trial registration ClinicalTrials.gov NCT05085288 Registered October 20, 2021.

Background The objective was to summarize the methodology used to reach consensus for recommended minimum data elements that should be collected and reported when conducting injury surveillance research in military settings. This paper summarizes the methodology used to develop the international Minimum Data Elements for surveillance and Reporting of Musculoskeletal Injuries in the MILitary (ROMMIL) statement. Methods A Delphi methodology was employed to reach consensus for minimum reporting elements. Preliminary steps included conducting a literature review and surveying a convenience sample of military stakeholders to 1) identify barriers and facilitators of military musculoskeletal injury (MSKI) prevention programs, 2) identify relevant knowledge/information gaps and 3) establish future research priorities. The team then led a sequential three-round Delphi consensus survey, including relevant stakeholders from militaries around the world, and then conducted asynchronous mixed knowledge user meeting to explore level of agreement among subject matter experts. Knowledge users, including former and current military service members, civil servant practitioners, and global-wide subject matter experts having experience with policy, execution, or clinical investigation of MSKI mitigation programs, MSKI diagnoses, and MSKI risk factors in military settings. For each round, participants scored each question on a Likert scale of 1-5. Scores ranged from No Importance (1) to Strong Importance (5). Results Literature review and surveys helped informed the scope of potential variables to vote on. Three rounds were necessary to reach minimum consensus. Ninety-five, 65 and 42 respondents participated in the first, second and third rounds of the Delphi consensus, respectively. Ultimately, consensus recommendations emerged consisting of one data principle and 33 minimum data elements. Conclusions Achieving consensus across relevant stakeholders representing military organizations globally can be challenging. This paper details the methodology employed to reach consensus for a core minimum data elements checklist for conducting MSKI research in military settings and improve data harmonization and scalability efforts. These methods can be used as a resource to assist in future consensus endeavors of similar nature.

Spinach is a crop of economic importance in the Wintergarden region of Texas, where increasing soil salinity, irrigation water restrictions, and heat stress challenge its production. Improving abiotic stress tolerance and resource use efficiency are important goals for sustainable agricultural production. Although the effect of humic substances (HS) on abiotic stress tolerance in spinach has been evaluated under single stress, such as heat, drought, or salinity, their impact under combined abiotic stresses is unknown. We hypothesized that solid humic substances would be effective in alleviating multifactorial abiotic stress in spinach, which we examined in our first experiment, and further hypothesized that salinity stress in spinach would occur after a threshold intensity but that humic substance applications would ameliorate stress intensity past this threshold, which we examined in our second experiment. Three-week-old spinach seedlings (Spinacia oleracea L. cv. ‘Seaside’) were grown using an automatic gravimetric watering system in a climate-controlled high tunnel where daily maximum temperatures exceeded 32 °C. In a factorial experiment, we applied HS (control and 1 % v/v HS media amendment), drought (100 % and 50 % field capacity), and salinity (25 mL of RO water or 100 mM NaCl every other day) treatments. HS and HS×Salinity treatments more than doubled shoot and root FW and DW, leaf area, root length, and root surface area compared to other stresses, indicating HS improved growth and stress tolerance. Improved growth was matched with improved resource use efficiency, as HS and HS×Salinity treated plants exhibited the greatest WUE. Drought stress also increased WUE relative to the control but lowered transpiration rate responses to VPD in contrasts to HS and HS×Salinity treated plants, which increased their transpiration rates in response to increasing VPD. Salinity treatments increased sodium content (Na+) in both shoots and roots. No HS effect was observed in shoot Na+ accumulation, but HS reduced Na+ in roots under the Drought×Salinity treatment. Strong interactions between drought and salinity were observed for shoot and root Na+, Na+/K+, and shoot K+, showing that spinach accumulates Na+ and reduces K+ when drought and salinity stress are combined. HS had no apparent effect on leaf metabolites. Drought and salinity differentially impacted MDA, proline, and antioxidant content and activities, while HS showed no effect. Drought stress significantly increased MDA and proline while reducing TPC, TFC, ABTS, and FRAP. Salinity stress significantly decreased MDA, TPC, ABTS, FICA, and FRAP. In conclusion, HS improved overall spinach growth and WUE while decreasing root Na accumulation, and subsequently enhancing spinach stress tolerance.

Much of the Earth and many surfaces of extraterrestrial bodies are composed of non-cohesive particulate matter. Locomoting on such granular terrain is challenging for common robotic devices, either wheeled or legged. In this work, we discover a robust alternative locomotion mechanism on granular media-generating movement via self-vibration. To demonstrate the effectiveness of this locomotion mechanism, we develop a cube-shaped robot with an embedded vibratory motor and conduct systematic experiments on granular terrains of various particle properties and slopes. We investigate how locomotion changes as a function of vibration frequency/intensity on such granular terrains. Compared to hard surfaces, we find such a vibratory locomotion mechanism enables the robot to move faster, and more stably on granular surfaces, facilitated by the interaction between the body and surrounding grains. We develop a numerical simulation of a vibrating single cube on granular media, enabling us to justify our hypothesis that the cube achieves locomotion through the oscillations excited at a distance from the cube’s center of mass. The simplicity in structural design and controls of this robotic system indicates that vibratory locomotion can be a valuable alternative way to produce robust locomotion on granular terrains. We further demonstrate that such cube-shaped robots can be used as modular units for vibratory robots with capabilities of maneuverable forward and turning motions, showing potential practical scenarios for robotic systems.

The past five years have yielded impressive advancements in fully absorbable metal stent technology. The desired ultimate ability for such devices to treat a vascular stenosis without long-term device-related complications or impeding future treatment continues to evoke excitement in clinicians and engineers alike. Nowhere is the need for fully absorbable metal stents greater than in patients experiencing vascular anomalies associated with congenital heart disease (CHD). Perhaps not surprisingly, commercially available absorbable metal stents have been implanted in pediatric cardiology patients with conditions ranging from pulmonary artery and vein stenosis to coarctation of the aorta and conduit/shunt reconstructions. Despite frequent short term procedural success, device performance has missed the mark with the commercially available devices not achieving degradation benchmarks for given applications. In this review we first provide a general overview detailing the theory of absorbable metal stents, and then review recent clinical use in CHD patients since the release of current-generation absorbable metal stents around 2019. We also discuss the challenges and our center's experience associated with the use of absorbable metal stents in this pediatric population. Lastly, we present potential directions for future engineering endeavors to mitigate existing challenges.

Engineered nanoparticles (NPs) pose a broad spectrum of interesting properties that make them useful for many applications. However, continuous exposure to NPs requires the need to deeply understand the outcomes when these NPs interact with different biological environments. After exposure within (to) these environments, the pristine surfaces of NPs strongly interact with the molecules from the surrounding medium, including metabolites, lipids, glycan, and proteins, forming the so-called protein corona (PC). It is well established that the NP-PC strongly influences the biological fate of various NPs types, including cellular uptake, toxicity, and biodistribution. Thus, for a proper assessment of potential hazards associated with engineered NPs, it is mandatory to study and evaluate the PC that forms around NPs. Herein, we describe protocols in detail for the isolation and characterization of NP-PC complexes and cover the following aspects: 1) isolation protocols for different nanomaterials in a range of exposing media, including magnetic isolation methods for superparamagnetic NPs, 2) NP physico-chemical characterization using advanced and standard techniques available in regular laboratories, and 3) NP- PC characterization of the protein and glycan components.

Background Outcomes from cardiopulmonary resuscitation (CPR) following sudden cardiac arrest are suboptimal. Postresuscitation targeted temperature management has been shown to have benefit in subjects with sudden cardiac arrest due to ventricular fibrillation, but there are few data for outcomes from sudden cardiac arrest due to pulseless electrical activity. In addition, intra‐CPR cooling is more effective than postresuscitation cooling. Physical cooling is associated with increased protein kinase B activity. Therefore, our group developed a novel peptide, TAT‐PHLPP9c, which regulates protein kinase B. We hypothesized that when given during CPR, TAT‐PHLPP9c would improve survival and neurologic outcomes following pulseless electrical activity arrest. Methods and Results In 24 female pigs, pulseless electrical activity was induced by inflating balloon catheters in the right coronary and left anterior descending arteries for ≈7 minutes. Advanced life support was initiated. In 12 control animals, epinephrine was given after 1 and 3 minutes. In 12 peptide‐treated animals, 7.5 mg/kg TAT‐PHLPP9c was also administered at 1 and 3 minutes of CPR. The balloons were removed after 2 minutes of support. Animals were recovered and neurologically scored 24 hours after return of spontaneous circulation. Return of spontaneous circulation was more common in the peptide group, but this difference was not significant (8/12 control versus 12/12 peptide; P=0.093), while fully intact neurologic survival was significantly more common in the peptide group (0/12 control versus 11/12 peptide; P

Abstract Sexual size dimorphism has motivated a large body of research on mammalian mating strategies and sexual selection. Despite some contrary evidence, the narrative that larger males are the norm in mammals—upheld since Darwin’s Descent of Man—still dominates today, supported by meta-analyses that use coarse measures of dimorphism and taxonomically-biased sampling. With newly-available datasets and primary sources reporting sex-segregated means and variances in adult body mass, we estimate statistically-determined rates of sexual size dimorphism in mammals, sampling taxa by their species richness at the family level. Our analyses of wild, non-provisioned populations representing >400 species indicate that although males tend to be larger than females when dimorphism occurs, males are not larger in most mammal species, suggesting a need to revisit other assumptions in sexual selection research.

Abstract Background Older adults with frailty have surgery at a high rate. Informal caregivers often support the postoperative transition in care. Despite the growing need for family and caregiver support for this population, little is known about the experience of providing informal care to older adults with frailty during the postoperative transition in care. The purpose of this study was to explore what is important during a postoperative transition in care for older adults with frailty from the perspective of informal caregivers. Methods This was a qualitative study using an interpretive description methodology. Seven informal caregivers to older adults [aged ≥ 65 years with frailty (Clinical Frailty Scale score ≥ 4) who had an inpatient elective surgery] participated in a telephone-based, semi-structured interview. Audio files were transcribed and analyzed using reflexive thematic analysis. Results Four themes were constructed: (1) being informed about what to expect after surgery; (2) accessible communication with care providers; (3) homecare resources are needed for the patient; and (4) a support network for the caregivers. Theme 4 included two sub-themes: (a) respite and emotional support and (b) occupational support. Conclusions Transitions in care present challenges for informal caregivers of older adults with frailty, who play an important role in successful transitions. Future postoperative transitional care programs should consider making targeted information, accessible communication, and support networks available for caregivers as part of facilitating successful transitions in care.

Background: People living with frailty are vulnerable to poor outcomes and incur higher health care costs after coronary artery bypass graft (CABG) surgery. Frailty-defining instruments for population-level research in the CABG setting have not been established. The objectives of the study were to develop a preoperative frailty index for CABG (pFI-C) surgery using Ontario administrative data; assess pFI-C suitability in predicting clinical and economic outcomes; and compare pFI-C predictive capabilities with other indices. Methods: A retrospective cohort study was conducted using health administrative data of 50,682 CABG patients. The pFI-C comprised 27 frailty-related health deficits. Associations between index scores and mortality, resource use and health care costs (2022 Canadian dollars [CAD]) were assessed using multivariable regression models. Capabilities of the pFI-C in predicting mortality were evaluated using concordance statistics; goodness of fit of the models was assessed using Akakie Information Criterion. Results: As assessed by the pFI-C, 22% of the cohort lived with frailty. The pFI-C score was strongly associated with mortality per 10% increase (odds ratio [OR], 3.04; 95% confidence interval [CI], [2.83,3.27]), and was significantly associated with resource utilization and costs. The predictive performances of the pFI-C, Charlson, and Elixhauser indices and Johns Hopkins Aggregated Diagnostic Groups were similar, and mortality models containing the pFI-C had a concordance (C)-statistic of 0.784. Cost models containing the pFI-C showed the best fit. Conclusions: The pFI-C is predictive of mortality and associated with resource utilization and costs during the year following CABG. This index could aid in identifying a subgroup of high-risk CABG patients who could benefit from targeted perioperative health care interventions. Résumé: Contexte: Les personnes dont l’état de santé est fragilisé sont susceptibles de connaître des issues défavorables et de générer des coûts plus élevés pour le système de santé après un pontage aortocoronarien. Aucun instrument n’a été établi pour définir la fragilité dans la recherche populationnelle en contexte de pontage aortocoronarien. Les objectifs de l’étude étaient les suivants : 1) concevoir un indice de fragilité préopératoire en vue d’un pontage aortocoronarien (preoperative frailty index for CABG surgery, pFI-C) en utilisant des données administratives de l’Ontario; 2) évaluer la capacité de cet indice à prédire les issues cliniques et économiques; et 3) comparer la valeur prédictive de cet indice avec celle d’autres indices. Méthodologie: Une étude de cohorte rétrospective a été menée à partir de données médico-administratives portant sur 50 682 patients ayant subi un pontage aortocoronarien. Le pFI-C comprenait 27 déficits de santé liés à la fragilité. Des liens entre les scores de l’indice et la mortalité, l’utilisation des ressources et les coûts de soins de santé (en $ CA de 2022) ont été évalués à l’aide de modèles de régression multivariable. La capacité du pFI-C à prédire la mortalité a été évaluée à l’aide de la statistique de concordance; la qualité de l’ajustement des modèles a été évaluée en fonction du critère d’information d’Akaike. Résultats: Selon l’évaluation par le pFI-C, 22 % de la cohorte vivait avec une fragilité. Le score de l’indice était fortement corrélé à la mortalité par tranche d’augmentation de 10 % (rapport de cotes de 3,04; intervalle de confiance à 95 % de 2,83 à 3,27) et était corrélé de manière significative à l’utilisation des ressources et aux coûts. La valeur prédictive du pFI-C, des indices de Charlson et Elixhauser, et de Johns Hopkins Aggregated Diagnostic Groups était similaire, et les modèles de mortalité contenant le pFI-C affichaient une valeur statistique C de 0,784. Les modèles de coûts contenant le pFI-C affichaient le meilleur ajustement. Conclusions: Le pFI-C est un facteur prédictif de mortalité et est corrélé à l’utilisation des ressources et aux coûts engagés durant l’année qui suit un pontage aortocoronarien. Cet indice pourrait faciliter la détection d’un sous-groupe de patients subissant un pontage aortocoronarien et présentant un risque élevé qui pourraient bénéficier de soins périopératoires ciblés.

Abstract To date only a fraction of the genetic footprint of thyroid function has been clarified. We report a genome-wide association study meta-analysis of thyroid function in up to 271,040 individuals of European ancestry, including reference range thyrotropin (TSH), free thyroxine (FT4), free and total triiodothyronine (T3), proxies for metabolism (T3/FT4 ratio) as well as dichotomized high and low TSH levels. We revealed 259 independent significant associations for TSH (61% novel), 85 for FT4 (67% novel), and 62 novel signals for the T3 related traits. The loci explained 14.1%, 6.0%, 9.5% and 1.1% of the total variation in TSH, FT4, total T3 and free T3 concentrations, respectively. Genetic correlations indicate that TSH associated loci reflect the thyroid function determined by free T3, whereas the FT4 associations represent the thyroid hormone metabolism. Polygenic risk score and Mendelian randomization analyses showed the effects of genetically determined variation in thyroid function on various clinical outcomes, including cardiovascular risk factors and diseases, autoimmune diseases, and cancer. In conclusion, our results improve the understanding of thyroid hormone physiology and highlight the pleiotropic effects of thyroid function on various diseases.

Abstract Background Uncovering the functional relevance underlying verbal declarative memory (VDM) genome-wide association study (GWAS) results may facilitate the development of interventions to reduce age-related memory decline and dementia. Methods We performed multi-omics and pathway enrichment analyses of paragraph (PAR-dr) and word list (WL-dr) delayed recall GWAS from 29,076 older non-demented individuals of European descent. We assessed the relationship between single-variant associations and expression quantitative trait loci (eQTLs) in 44 tissues and methylation quantitative trait loci (meQTLs) in the hippocampus. We determined the relationship between gene associations and transcript levels in 53 tissues, annotation as immune genes, and regulation by transcription factors (TFs) and microRNAs. To identify significant pathways, gene set enrichment was tested in each cohort and meta-analyzed across cohorts. Analyses of differential expression in brain tissues were conducted for pathway component genes. Results The single-variant associations of VDM showed significant linkage disequilibrium (LD) with eQTLs across all tissues and meQTLs within the hippocampus. Stronger WL-dr gene associations correlated with reduced expression in four brain tissues, including the hippocampus. More robust PAR-dr and/or WL-dr gene associations were intricately linked with immunity and were influenced by 31 TFs and 2 microRNAs. Six pathways, including type I diabetes, exhibited significant associations with both PAR-dr and WL-dr. These pathways included fifteen MHC genes intricately linked to VDM performance, showing diverse expression patterns based on cognitive status in brain tissues. Conclusions VDM genetic associations influence expression regulation via eQTLs and meQTLs. The involvement of TFs, microRNAs, MHC genes, and immune-related pathways contributes to VDM performance in older individuals.

Abstract X-chromosomal genetic variants are understudied but can yield valuable insights into sexually dimorphic human traits and diseases. We performed a sex-stratified cross-ancestry X-chromosome-wide association meta-analysis of seven kidney-related traits (n = 908,697), identifying 23 loci genome-wide significantly associated with two of the traits: 7 for uric acid and 16 for estimated glomerular filtration rate (eGFR), including four novel eGFR loci containing the functionally plausible prioritized genes ACSL4, CLDN2, TSPAN6 and the female-specific DRP2. Further, we identified five novel sex-interactions, comprising male-specific effects at FAM9B and AR/EDA2R, and three sex-differential findings with larger genetic effect sizes in males at DCAF12L1 and MST4 and larger effect sizes in females at HPRT1. All prioritized genes in loci showing significant sex-interactions were located next to androgen response elements (ARE). Five ARE genes showed sex-differential expressions. This study contributes new insights into sex-dimorphisms of kidney traits along with new prioritized gene targets for further molecular research.

Objective:. This study evaluated the association between preoperative education and adherence to downstream components of enhanced recovery programs (ERPs) and surgical outcomes among patients undergoing elective colorectal surgery. Background:. ERPs improve outcomes for surgical patients. While preoperative education is an essential component of ERPs, its relationship with other components is unclear. Methods:. This was a retrospective cohort study of all ERP patients undergoing elective colorectal surgery from 2019 to 2022. Our institutional ERP database was linked with American College of Surgeons National Surgical Quality Improvement Program data and stratified by adherence to preoperative education. Primary outcomes included adherence to individual ERP components and secondary outcomes included high-level ERP adherence (>70% of components), length of stay (LOS), readmissions, and 30-day complications. Results:. A total of 997 patients were included. The mean (SD) age was 56.5 (15.8) years, 686 (57.3%) were female, and 717 (71.9%) were white. On adjusted analysis, patients who received preoperative education (n = 877, 88%) had higher adherence rates for the following ERP components: no prolonged fasting (estimate = +19.6%; P < 0.001), preoperative blocks (+8.0%; P = 0.02), preoperative multimodal analgesia (+18.0%; P < 0.001), early regular diet (+15.9%; P < 0.001), and postoperative multimodal analgesia (+6.4%; P < 0.001). High-level ERP adherence was 13.4% higher (P < 0.01) and LOS was 2.0 days shorter (P < 0.001) for those who received preoperative education. Classification and regression tree analysis identified preoperative education as the first-level predictor for adherence to early regular diet, the second-level predictor for LOS, and the third-level predictor for ERP high-level adherence. Conclusion:. Preoperative education is associated with adherence to ERP components and improved surgical outcomes.

Objective:. To determine timing and risk factors associated with readmission within 30 days of discharge following noncardiac surgery. Background:. Hospital readmission after noncardiac surgery is costly. Data on the drivers of readmission have largely been derived from single-center studies focused on a single surgical procedure with uncertainty regarding generalizability. Methods:. We undertook an international (28 centers, 14 countries) prospective cohort study of a representative sample of adults ≥45 years of age who underwent noncardiac surgery. Risk factors for readmission were assessed using Cox regression (ClinicalTrials.gov, NCT00512109). Results:. Of 36,657 eligible participants, 2744 (7.5%; 95% confidence interval [CI], 7.2–7.8) were readmitted within 30 days of discharge. Rates of readmission were highest in the first 7 days after discharge and declined over the follow-up period. Multivariable analyses demonstrated that 9 baseline characteristics (eg, cancer treatment in past 6 months; adjusted hazard ratio [HR], 1.44; 95% CI, 1.30–1.59), 5 baseline laboratory and physical measures (eg, estimated glomerular filtration rate or on dialysis; HR, 1.47; 95% CI, 1.24–1.75), 7 surgery types (eg, general surgery; HR, 1.86; 95% CI, 1.61–2.16), 5 index hospitalization events (eg, stroke; HR, 2.21; 95% CI, 1.24–3.94), and 3 other factors (eg, discharge to nursing home; HR, 1.61; 95% CI, 1.33–1.95) were associated with readmission. Conclusions:. Readmission following noncardiac surgery is common (1 in 13 patients). We identified perioperative risk factors associated with 30-day readmission that can help frontline clinicians identify which patients are at the highest risk of readmission and target them for preventive measures.

Abstract Eco‐evolutionary experiments are typically conducted in semi‐unnatural controlled settings, such as mesocosms; yet inferences about how evolution and ecology interact in the real world would surely benefit from experiments in natural uncontrolled settings. Opportunities for such experiments are rare but do arise in the context of restoration ecology—where different “types” of a given species can be introduced into different “replicate” locations. Designing such experiments requires wrestling with consequential questions. (Q1) Which specific “types” of a focal species should be introduced to the restoration location? (Q2) How many sources of each type should be used—and should they be mixed together? (Q3) Which specific source populations should be used? (Q4) Which type(s) or population(s) should be introduced into which restoration sites? We recently grappled with these questions when designing an eco‐evolutionary experiment with threespine stickleback (Gasterosteus aculeatus) introduced into nine small lakes and ponds on the Kenai Peninsula in Alaska that required restoration. After considering the options at length, we decided to use benthic versus limnetic ecotypes (Q1) to create a mixed group of colonists from four source populations of each ecotype (Q2), where ecotypes were identified based on trophic morphology (Q3), and were then introduced into nine restoration lakes scaled by lake size (Q4). We hope that outlining the alternatives and resulting choices will make the rationales clear for future studies leveraging our experiment, while also proving useful for investigators considering similar experiments in the future.

A crop boom is a sudden, nonlinear and intense expansion of a new crop. Despite their large impacts, boom-bust dynamics are not well understood; booms are largely unpredictable and difficult to steer once they unfold. Based on the striking resemblances between land regime shifts and crop booms, we apply complex systems theory, highlighting the potential for regime shifts, to provide new insights about crop boom dynamics. We analyse qualitative and quantitative data of rubber and banana plantation expansion in two forest frontier regions of northern Laos. We show that preconditions, including previous booms, explain the occurrence (why) of booms, and triggers like policy and market changes explain their timing (when). Yet, the most important features of booms, their intensity and nonlinearity (how), strongly depended on internal self-reinforcing feedbacks. We identify built-in feedbacks (neighbourhood effects and imitation) and emergent feedbacks (land rush) and show that they were social in nature, multi-scale from plot to region and subject to thresholds. We suggest that these are regular features of booms and propose a definition and causal-mechanistic explanation of crop booms, examining the overlap between booms and regime shifts and the role of frontiers. We then identify opportunities for management interventions before, during and after booms.

Introduction Tranexamic acid (TXA) is an inexpensive and widely available medication that reduces blood loss and red blood cell (RBC) transfusion in cardiac and orthopaedic surgeries. While the use of TXA in these surgeries is routine, its efficacy and safety in other surgeries, including oncologic surgeries, with comparable rates of transfusion are uncertain. Our primary objective is to evaluate whether a hospital-level policy implementation of routine TXA use in patients undergoing major non-cardiac surgery reduces RBC transfusion without increasing thrombotic risk.Methods and analysis A pragmatic, registry-based, blinded, cluster-crossover randomised controlled trial at 10 Canadian sites, enrolling patients undergoing non-cardiac surgeries at high risk for RBC transfusion. Sites are randomised in 4-week intervals to a hospital policy of intraoperative TXA or matching placebo. TXA is administered as 1 g at skin incision, followed by an additional 1 g prior to skin closure. Coprimary outcomes are (1) effectiveness, evaluated as the proportion of patients transfused RBCs during hospital admission and (2) safety, evaluated as the proportion of patients diagnosed with venous thromboembolism within 90 days. Secondary outcomes include: (1) transfusion: number of RBC units transfused (both at a hospital and patient level); (2) safety: in-hospital diagnoses of myocardial infarction, stroke, deep vein thrombosis or pulmonary embolism; (3) clinical: hospital length of stay, intensive care unit admission, hospital survival, 90-day survival and the number of days alive and out of hospital to day 30; and (4) compliance: the proportion of enrolled patients who receive a minimum of one dose of the study intervention.Ethics and dissemination Institutional research ethics board approval has been obtained at all sites. At the completion of the trial, a plain language summary of the results will be posted on the trial website and distributed in the lay press. Our trial results will be published in a peer-reviewed scientific journal.Trial registration number NCT04803747.

The transient hypoxic-ischemic attack, also known as a minor stroke, can result in long-term neurological issues such as memory loss, depression, and anxiety due to an increase in nitrosative stress. The individual or combined administration of chronic prophylactic zinc and therapeutic selenium is known to reduce nitrosative stress in the first seven days post-reperfusion and, due to an antioxidant effect, prevent cell death. Besides, zinc or selenium, individually administered, also causes antidepressant and anxiolytic effects. Therefore, this work evaluated whether combining zinc and selenium could prevent stroke-elicited cognition and behavior deficits after 30 days post-reperfusion. Accordingly, we assessed the expression of growth factors at 7 days post-reperfusion, a four-time course of memory (from 7 to 28 days post-learning test), and cell proliferation, depression, and anxiety-like behavior at 30 days post-reperfusion. Male Wistar rats with a weight between 190 and 240 g) were treated with chronic prophylactic zinc administration with a concentration of 0.2 mg/kg for 15 days before common carotid artery occlusion (10 min) and then with therapeutic selenium (6 μg/kg) for 7 days post-reperfusion. Compared with individual administrations, the administration combined of prophylactic zinc and therapeutic selenium decreased astrogliosis, increased growth factor expression, and improved cell proliferation and survival in two regions, the hippocampus, and cerebral cortex. These effects prevented memory loss, depression, and anxiety-like behaviors. In conclusion, these results demonstrate that the prophylactic zinc administration combined with therapeutic selenium can reduce the long-term sequelae caused by the transient ischemic attack.Significance statement.A minor stroke caused by a transient ischemic attack can result in psychomotor sequelae that affect not only the living conditions of patients and their families but also the economy. The incidence of these micro-events among young people has increased in the world. Nonetheless, there is no deep understanding of how this population group responds to regular treatments (Ekker and et al., 2018) [1]. On the basis that zinc and selenium have antioxidant, anti-inflammatory, and regenerative properties in stroke animal models, our work explored whether the chronic combined administration of prophylactic zinc and therapeutic selenium could prevent neurological sequelae in the long term in a stroke rat model of unilateral common carotid artery occlusion (CCAO) by 10-min. Our results showed that this combined treatment provided a long-term neuroprotective effect by decreasing astrogliosis, memory loss, anxiety, and depression-like behavior.

The first case of cerebral venous thrombosis, described in the past century, was identified in obstetric patients in 1825. The clinical manifestations represent a real diagnostic challenge due to the few recorded cases, the wide variety of possible clinical symptoms, and the diversity of medical conditions that cause it. In the past century, the etiology was mainly associated with septic processes; however, due to the widespread use of antibiotics, this cause has been considerably reduced. In the context of the puerperium, several conditions make this group of patients more vulnerable, such as dehydration, hypercoagulable state, iron deficiency, puerperal sepsis, and preeclampsia, the latter is particularly known for an endothelial lesion with different degrees of associated severity, according to the clinical phenotype present. This review aims to highlight the most relevant aspects of cerebral thrombosis in the context of a puerperal patient. It will also present clinical cases reports treated successfully in this health unit.

Established in 1985, the Cross-Commodity Publication Award recognizes authors of the most outstanding paper on horticultural cross-commodity research, including broadly applicable methodology, pre- and postharvest physiology, genetics, anatomy, morphology, ecology, crop production systems, modeling, and management, published in the previous year’s issues of the Journal of the American Society for Horticultural Science (JASHS), HortScience, or HortTechnology. Through the 39-year span (1985–2023), there were 38 papers that have been awarded (Table 1). Among all papers, two of them were published in HortTechnology, nine in HortScience, and 27 in the JASHS. Most of the awarded papers were basic research, which was aiming to understand the occurrence of a phenomenon and the response of plants; and applicable methodology, which was developed to facilitate efficient phenotyping or plant propagation and production. In addition, most of the studies were conducted under controlled environment and laboratory conditions, and there were several papers studying multiple crops spanning from fruits, vegetables, and ornamentals within one experimental set.

AIMS: Patients undergoing emergency general surgery are at high risk of complications and death. Our objectives were to estimate the incidence of emergency general surgery in a Swiss University Hospital, to describe the characteristics and outcomes of patients undergoing such procedures, and to study the impact of age on clinical outcomes. METHODS: This was a retrospective cohort study of adult patients who visited the emergency department (ED) of Geneva University Hospitals between January 2015 and December 2019. Routinely collected data were extracted from electronic medical records. The primary outcome was the incidence of emergency general surgery among patients visiting the emergency department, defined as general surgery within three days of emergency department admission. We also assessed demographic characteristics, mortality, intensive care unit admission and patient disposition. Multivariable log-binomial regression was used to study the associations of age with intensive care unit (ICU) admission, one-year mortality and dependence at discharge. Age was modelled as a continuous variable using restricted cubic splines and we compared older patients (75th percentile) with younger patients (25th percentile). RESULTS: Between January 2015 and December 2019, a total of 310,914 emergency department visits met our inclusion criteria. Among them, 3592 patients underwent emergency general surgery within 3 days of emergency department admission, yielding an annual incidence of 116 events per 10,000 emergency department visits (95% CI: 112–119), with a higher incidence in females and young patients. Overall, 5.3% of patients were admitted to ICU, 7.8% were dependent on rehabilitation or assisted living at discharge and 4.8% were dead after one year. Older patients had a higher risk of ICU admission (adjusted risk ratio (aRR) 2.9 [1.5–5.4]), dependence at discharge (aRR 15.3 [5.5–42.4]) and one-year mortality (aRR 5.4 [2.2–13.4]). CONCLUSION: Emergency department visits resulting in emergency general surgery are frequent, but their incidence decreases with patient age. Mortality, ICU admission and dependence at discharge following emergency general surgery are more frequent in older patients. Taking into account the increased risk for older patients, a shared process is appropriate for making more informed decisions about their options for care.

BackgroundMigraine has an increased prevalence in several immune disorders, but genetic cause-effect relationships remain unclear. Mendelian randomization (MR) was used in this study to explore whether immune diseases are causally associated with migraine and its subtypes.MethodsWe conducted a two-sample bidirectional multivariate Mendelian randomization study. Single-nucleotide polymorphisms (SNP) for six immune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type 1 diabetes mellitus (T1D), allergic rhinitis (AR), asthma and psoriasis, were used as genetic instrumental variables. Summary statistics for migraine were obtained from 3 databases: the International Headache Genetics Consortium (IHGC), UK Biobank, and FinnGen study. MR analyses were performed per outcome database for each exposure and subsequently meta-analyzed. Reverse MR analysis was performed to determine whether migraine were risk factors for immune diseases. In addition, we conducted a genetic correlation to identify shared genetic variants for these two associations.ResultsNo significant causal relationship was found between immune diseases and migraine and its subtypes. These results were robust with a series of sensitivity analyses. Using the linkage disequilibrium score regression method (LDSC), we detected no genetic correlation between migraine and immune diseases.ConclusionThe evidence from our study does not support a causal relationship between immune diseases and migraine. The mechanisms underlying the frequent comorbidity of migraine and several immune diseases need to be further elucidated.

Abstract Background Adults aged 65 and older have surgery more often than younger people and often live with frailty. The postoperative transition in care from hospital to home after surgey is a challenging time for older adults with frailty as they often experience negative outcomes. Improving postoperative transitions in care for older adults with frailty is a priority. However, little knowledge from the perspective of older adults with frailty is available to support meaningful improvements in postoperative transitions in care. Objective To explore what is important to older adults with frailty during a postoperative transition in care. Methods This qualitative study used an interpretive description methodology. Twelve adults aged ≥ 65 years with frailty (Clinical Frailty Scale score ≥ 4) who had an inpatient elective surgery and could speak in English participated in a telephone-based, semi-structured interview. Audio files were transcribed and analyzed using thematic analysis. Results Five themes were constructed: 1) valuing going home after surgery; 2) feeling empowered through knowledge and resources; 3) focusing on medical and functional recovery; 4) informal caregivers and family members play multiple integral roles; and 5) feeling supported by healthcare providers through continuity of care. Each theme had 3 sub-themes. Conclusion Future programs should focus on supporting patients to return home by empowering patients with resources and clear communication, ensuring continuity of care, creating access to homecare and virtual support, focusing on functional and medical recovery, and recognizing the invaluable role of informal caregivers.

Abstract Systems consisting of spheres rolling on elastic membranes have been used to introduce a core conceptual idea of General Relativity: how curvature guides the movement of matter. However, such schemes cannot accurately represent relativistic dynamics in the laboratory because of the dominance of dissipation and external gravitational fields. Here we demonstrate that an “active” object (a wheeled robot), which moves in a straight line on level ground and can alter its speed depending on the curvature of the deformable terrain it moves on, can exactly capture dynamics in curved relativistic spacetimes. Via the systematic study of the robot’s dynamics in the radial and orbital directions, we develop a mapping of the emergent trajectories of a wheeled vehicle on a spandex membrane to the motion in a curved spacetime. Our mapping demonstrates how the driven robot’s dynamics mix space and time in a metric, and shows how active particles do not necessarily follow geodesics in the real space but instead follow geodesics in a fiducial spacetime. The mapping further reveals how parameters such as the membrane elasticity and instantaneous speed allow the programming of a desired spacetime, such as the Schwarzschild metric near a non-rotating blackhole. Our mapping and framework facilitate creation of a robophysical analog to a general relativistic system in the laboratory at low cost that can provide insights into active matter in deformable environments and robot exploration in complex landscapes.

Abstract Plutonium (Pu) cycling and mobility in the environment can be impacted by the iron cycle and microbial community dynamics. We investigated the spatial and temporal changes of the microbiome in an iron (Fe)-rich, plutonium-contaminated, monomictic reservoir (Pond B, Savannah River Site, South Carolina, USA). The microbial community composition varied with depth during seasonal thermal stratification and was strongly correlated with redox. During stratification, Fe(II) oxidizers (e.g., Ferrovum, Rhodoferax, Chlorobium) were most abundant in the hypoxic/anoxic zones, while Fe(III) reducers (e.g., Geothrix , Geobacter) dominated the deep, anoxic zone. Sulfate reducers and methanogens were present in the anoxic layer, likely contributing to iron and plutonium cycling. Multinomial regression of predicted functions/pathways identified metabolisms highly associated with stratification (within the top 5%), including iron reduction, methanogenesis, C1 compound utilization, fermentation, and aromatic compound degradation. Two sediment cores collected at the Inlet and Outlet of the pond were dominated by putative fermenters and organic matter (OM) degraders. Overall, microbiome analyses revealed the potential for three microbial impacts on the plutonium and iron biogeochemical cycles: (1) plutonium bioaccumulation throughout the water column, (2) Pu–Fe-OM-aggregate formation by Fe(II) oxidizers under microaerophilic/aerobic conditions, and (3) Pu–Fe-OM-aggregate or sediment reductive dissolution and organic matter degradation in the deep, anoxic waters.

Abstract Background Inadequate study reporting precludes interpretation of findings, pooling of results in meta-analyses, and delays knowledge translation. While prehabilitation interventions aim to enhance candidacy for surgery, to our knowledge, a review of the quality of reporting in prehabilitation has yet to be conducted. Our objective was to determine the extent to which randomized controlled trials (RCTs) of prehabilitation are reported according to methodological and intervention reporting checklists. Methods Eligibility criteria: RCTs of unimodal or multimodal prehabilitation interventions. Sources of evidence: search was conducted in March 2022 using MEDLINE, Embase, PsychINFO, Web of Science, CINAHL, and Cochrane. Charting methods: identified studies were compared to CONSORT, CERT & Modified CERT, TIDieR, PRESENT, and CONSORT-SPI. An agreement ratio (AR) was defined to evaluate if applicable guideline items were correctly reported. Data were analyzed as frequency (n, %) and mean with standard deviation (SD). Results We identified 935 unique articles and included 70 trials published from 1994 to 2022. Most prehabilitation programs comprised exercise-only interventions (n = 40, 57%) and were applied before oncologic surgery (n = 32, 46%). The overall mean AR was 57% (SD: 20.9%). The specific mean ARs were as follows: CONSORT: 71% (SD: 16.3%); TIDieR: 62% (SD:17.7%); CERT: 54% (SD: 16.6%); Modified-CERT: 40% (SD:17.8%); PRESENT: 78% (SD: 8.9); and CONSORT-SPI: 47% (SD: 22.1). Conclusion Altogether, existing prehabilitation trials report approximately half of the checklist items recommended by methodological and intervention reporting guidelines. Reporting practices may improve with the development of a reporting checklist specific to prehabilitation interventions.

Abstract Aims Specialist cardiology care is associated with a prognostic benefit in patients with heart failure (HF) with reduced ejection fraction (HFrEF) admitted with decompensated HF. However, up to one third of patients admitted with HF and normal ejection fraction (HFnEF) do not receive specialist cardiology input. Whether this has prognostic implications is unknown. Methods and results Data on patients hospitalized with HFnEF from two tertiary centres were analysed. The primary outcome measure was all‐cause mortality during follow‐up. The secondary outcome was in‐hospital mortality. A total of 1413 patients were included in the study. Of these, 23% (n = 322) did not receive in‐hospital specialist cardiology input. Patients seen by a cardiologist were less likely to have hypertension (73% vs. 79%, P = 0.03) and respiratory co‐morbidities (25% vs. 31%, P = 0.02) compared with those who did not receive specialist input. Similarly, clinical presentation was more severe for those who received specialist input (New York Heart Association III/IV 83% vs. 75% respectively, P = 0.003; moderate‐to‐severe peripheral oedema 65% vs. 54%, P

Abstract Unlike short-term laboratory experiments, studies at sites historically contaminated with radionuclides can provide insight into contaminant migration behavior at environmentally-relevant decadal timescales. One such site is Pond B, a seasonally stratified reservoir within Savannah River Site (SC, USA) has low levels (μBq L−1) of plutonium in the water column. Here, we evaluate the origin of plutonium using high-precision isotope measurements, investigate the impact of water column geochemistry on plutonium cycling during different stratification periods, and re-evaluate long-term mass balance of plutonium in the pond. New isotopic data confirm that reactor-derived plutonium overwhelms input from Northern Hemisphere fallout at this site. Two suggested mechanisms for observed plutonium cycling in the water column include: (1) reductive dissolution of sediment-derived Fe(III)-(oxyhydr)oxides during seasonal stratification and (2) plutonium stabilization complexed strongly to Fe(III)-particulate organic matter (POM) complexes. While plutonium may be mobilized to a limited extent by stratification and reductive dissolution, peak plutonium concentrations are in shallow waters and associated with Fe(III)-POM at the inception of stratification. This suggests that plutonium release from sediments during stratification is not the dominant mechanism driving plutonium cycling in the pond. Importantly, our analysis suggests that the majority is retained in shallow sediments and may become increasingly recalcitrant.

Transition metal oxides have found application as charge transport materials (CTMs) in perovskite solar cell devices due to their better environmental stability and superior electronic properties compared to organic CTMs. Many researchers have used radio frequency (RF) magnetron sputtering to deposit inorganic CTMs on inorganic layers. However, such efforts on perovskites have been limited by the distortion of high‐energy ions of the sputtering gas energized by the RF power and temperature. The ions may also distort the interface between transparent conducting oxides and the charge transport layers, thereby increasing optical scattering. Thus, the effect of ramp power during RF magnetron sputtering deposition on the structural and optical properties of copper oxide thin films is investigated. While the optical transmittance of the films decreases with increased RF power, it remains the same for all ramped power films; however, it has a similar profile as the highest RF power film. As the ramp power increases, the X‐ray diffraction shows that the films become more polycrystalline with a monoclinic crystal structure. The energy‐dispersive X‐ray spectroscopy results reveal that the atomic concentration of copper slightly increases with the RF power, whereas oxygen concentration slightly decreases.

ABSTRACT The bacteria within supragingival biofilms participate in complex exchanges with other microbes inhabiting the same niche. One example is the mutans group streptococci (Streptococcus mutans), implicated in the development of tooth decay, and other health-associated commensal streptococci species. Previously, our group transcriptomically characterized intermicrobial interactions between S. mutans and several species of oral bacteria. However, these experiments were carried out in a medium without human saliva. To better mimic their natural environment, we first evaluated how inclusion of saliva affected growth and biofilm formation of eight Streptococcus species individually and found saliva to positively benefit growth rates while negatively influencing biofilm biomass accumulation and altering spatial arrangement. These results carried over during evaluation of 29 saliva-derived isolates of various species. Surprisingly, we also found that addition of saliva increased the competitive behaviors of S. mutans in coculture competitions against commensal streptococci that led to increases in biofilm microcolony volumes. Through transcriptomically characterizing mono- and cocultures of S. mutans and Streptococcus oralis with and without saliva, we determined that each species developed a nutritional niche under mixed-species growth, with S. mutans upregulating carbohydrate uptake and utilization pathways while S. oralis upregulated genome features related to peptide uptake and glycan foraging. S. mutans also upregulated genes involved in oxidative stress tolerance, particularly manganese uptake, which we could artificially manipulate by supplementing in manganese leading to an advantage over its opponent. Our report highlights observable changes in microbial behaviors through leveraging environmental- and host-supplied resources over their competitors.IMPORTANCEDental caries (tooth decay) is the most prevalent disease for both children and adults nationwide. Caries are initiated from demineralization of the enamel due to organic acid production through the metabolic activity of oral bacteria growing in biofilm communities attached to the tooth’s surface. Mutans group streptococci are closely associated with caries development and initiation of the cariogenic cycle, which decreases the amount of acid-sensitive, health-associated commensal bacteria while selecting for aciduric and acidogenic species that then further drives the disease process. Defining the exchanges that occur between mutans group streptococci and oral commensals in a condition that closely mimics their natural environment is of critical need toward identifying factors that can influence odontopathogen establishment, persistence, and outgrowth. The goal of our research is to develop strategies, potentially through manipulation of microbial interactions characterized here, that prevent the emergence of mutans group streptococci while keeping the protective flora intact.