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Brain aging process is influenced by various lifestyle, environmental and genetic factors, as well as by age-related and often coexisting pathologies. Magnetic resonance imaging and artificial intelligence methods have been instrumental in understanding neuroanatomical changes that occur during aging. Large, diverse population studies enable identifying comprehensive and representative brain change patterns resulting from distinct but overlapping pathological and biological factors, revealing intersections and heterogeneity in affected brain regions and clinical phenotypes. Herein, we leverage a state-of-the-art deep-representation learning method, Surreal-GAN, and present methodological advances and extensive experimental results elucidating brain aging heterogeneity in a cohort of 49,482 individuals from 11 studies. Five dominant patterns of brain atrophy were identified and quantified for each individual by respective measures, R-indices. Their associations with biomedical, lifestyle and genetic factors provide insights into the etiology of observed variances, suggesting their potential as brain endophenotypes for genetic and lifestyle risks. Furthermore, baseline R-indices predict disease progression and mortality, capturing early changes as supplementary prognostic markers. These R-indices establish a dimensional approach to measuring aging trajectories and related brain changes. They hold promise for precise diagnostics, especially at preclinical stages, facilitating personalized patient management and targeted clinical trial recruitment based on specific brain endophenotypic expression and prognosis.

Therapeutic strategies for early-stage non-small cell lung cancer (NSCLC) are advancing, with immune checkpoint inhibitors (ICIs) and targeted therapies making their way into neoadjuvant and adjuvant settings. With recent advances, there was a need for multidisciplinary lung cancer healthcare providers from across Ontario to convene and review recent data from practical and implementation standpoints. The focus was on the following questions: (1) To what extent do patient (e.g., history of smoking) and disease (e.g., histology, tumor burden, nodal involvement) characteristics influence treatment approaches? (2) What are the surgical considerations in early-stage NSCLC? (3) What is the role of radiation therapy in the context of recent evidence? (4) What is the impact of biomarker testing on treatment planning? Ongoing challenges, treatment gaps, outstanding questions, and controversies with the data were assessed through a pre-meeting survey, interactive cases, and polling questions. By reviewing practice patterns across Ontario cancer centers in the context of evolving clinical data, Health Canada indications, and provincial (Cancer Care Ontario [CCO]) funding approvals, physicians treating lung cancer voiced their opinions on how new approaches should be integrated into provincial treatment algorithms. This report summarizes the forum outcomes, including pre-meeting survey and polling question results, as well as agreements on treatment approaches based on specific patient scenarios.

Medulloblastoma, a malignant pediatric brain tumor, has a poor prognosis upon relapse, highlighting a critical clinical need. Our previous research linked medulloblastoma cell radioresistance to integrin-αvβ3 expression. β3-depleted (β3_KO) medulloblastoma cells exhibit lipid hydroxyperoxide accumulation after radiotherapy, indicating ferroptosis, a regulated cell death induced by ROS and inhibited by antioxidants such as cysteine, glutathione (GSH), and glutathione peroxidase 4 (GPx4). However, the link between αvβ3 expression, ferroptosis inhibition, and sensitivity to radiotherapy remains unclear. We showed that irradiated β3_KO medulloblastoma cells primarily die by ferroptosis, with β3-subunit expression correlating with radiotherapy sensitivity and anti-ferroptotic protein levels. Our findings suggest that integrin-αvβ3 signaling boosts oxidative stress resilience via mTORC1. Thus, targeting integrin-αvβ3 could enhance radiotherapy efficacy in medulloblastoma by inducing ferroptotic cell death.

Abstract Effective approaches are needed to conserve the planet's remaining wildlife and wilderness landscapes, especially concerning global biodiversity conservation targets. Here, we present a new software system called EarthRanger: an open‐source platform built to help monitor, research and manage ecosystems. EarthRanger consists of seven main components (Core Server, API, Storage, Gundi, Web App, Mobile App, Ecoscope) that provide functionality for data (i) aggregation & collection, (ii) storage & management, (iii) real‐time and post hoc analysis, (iv) visualisation and (v) dissemination. The mobile application provides field‐based data recording and visualisation tools. EarthRanger may be deployed for single project use or can aggregate across multiple geographies as a centralised hub. EarthRanger can be used to collect standardised tracking data (e.g. from wildlife collars, vehicles and ranger patrols) and configurable event information (e.g. a singular recording with associated user‐defined attribute information such as a wildlife sighting or encounter with a poacher). Since development began in 2015, the platform has (at the time of writing) been deployed at over 500 sites across 70 countries and with myriad configurations and objectives. EarthRanger has improved the ability to monitor data feeds and manage conservation‐related operations in real time. For instance, the deployment of EarthRanger by African Parks has led to the removal of over 50,000 snares, steady population growth of key species of concern and near cessation of poaching. In Liwonde's protected area, enhanced mitigation efforts supported by EarthRanger reduced the number of deaths from wildlife conflict by more than 91%. EarthRanger is also providing a platform to enhance standardisation, aggregation, transfer and long‐term storage of ecological information and promote collaboration between groups conducting protected area management and ecology and biodiversity research.

Abstract Alzheimer’s disease (AD) is associated with heterogeneous atrophy patterns. We employed a semi-supervised representation learning technique known as Surreal-GAN, through which we identified two latent dimensional representations of brain atrophy in symptomatic mild cognitive impairment (MCI) and AD patients: the “diffuse-AD” (R1) dimension shows widespread brain atrophy, and the “MTL-AD” (R2) dimension displays focal medial temporal lobe (MTL) atrophy. Critically, only R2 was associated with widely known sporadic AD genetic risk factors (e.g., APOE ε4) in MCI and AD patients at baseline. We then independently detected the presence of the two dimensions in the early stages by deploying the trained model in the general population and two cognitively unimpaired cohorts of asymptomatic participants. In the general population, genome-wide association studies found 77 genes unrelated to APOE differentially associated with R1 and R2. Functional analyses revealed that these genes were overrepresented in differentially expressed gene sets in organs beyond the brain (R1 and R2), including the heart (R1) and the pituitary gland, muscle, and kidney (R2). These genes were enriched in biological pathways implicated in dendritic cells (R2), macrophage functions (R1), and cancer (R1 and R2). Several of them were “druggable genes” for cancer (R1), inflammation (R1), cardiovascular diseases (R1), and diseases of the nervous system (R2). The longitudinal progression showed that APOE ε4, amyloid, and tau were associated with R2 at early asymptomatic stages, but this longitudinal association occurs only at late symptomatic stages in R1. Our findings deepen our understanding of the multifaceted pathogenesis of AD beyond the brain. In early asymptomatic stages, the two dimensions are associated with diverse pathological mechanisms, including cardiovascular diseases, inflammation, and hormonal dysfunction—driven by genes different from APOE—which may collectively contribute to the early pathogenesis of AD. All results are publicly available at https://labs-laboratory.com/medicine/ .

In Malaysian secondary education, typically only academically able students with learning disabilities and acceptable behaviour join mainstream classrooms for full inclusion. Social participation at school is one key indicator of inclusive education outcomes. Most Malaysian mainstream classrooms group students into small fixed peer-seating groups. This group could represent one support for social participation available to students with learning disabilities (LD) in inclusion classrooms. However, nothing is currently known about the views and experiences of social participation from the perspective of Malaysian students with LD or about the support provided by their peer-seating group in mainstream classrooms. We investigated the social participation of four focal students with LD in two Malaysian inclusive secondary schools, using a qualitative multiple case study design. The peer-seating group played a prominent role in focal students' social participation. Several themes identified in the analysis revealed the peer-seating group's facilitation of social participation (i.e. close contact with peer-seating group; working together on tasks; free time together), but other themes identified obstacles (i.e. limited or absent friendship network). This study contributes to a better understanding of the school social participation experiences of Malaysian adolescents with LD.

IntroductionWe examined whether sex modifies the association between APOE ε2 and cognitive decline in two independent samples.MethodsWe used observational data from cognitively unimpaired non-Hispanic White (NHW) and non-Hispanic Black (NHB) adults. Linear mixed models examined interactive associations of APOE genotype (ε2 or ε4 carrier vs. ε3/ε3) and sex on cognitive decline in NHW and NHB participants separately.ResultsIn both Sample 1 (N = 9766) and Sample 2 (N = 915), sex modified the association between APOE ε2 and cognitive decline in NHW participants. Specifically, relative to APOE ε3/ε3, APOE ε2 protected against cognitive decline in men but not women. Among APOE ε2 carriers, men had slower decline than women. Among APOE ε3/ε3 carriers, cognitive trajectories did not differ between sexes. There were no sex-specific associations of APOE ε2 with cognition in NHB participants (N = 2010).DiscussionIn NHW adults, APOE ε2 may protect men but not women against cognitive decline.HighlightsWe studied sex-specific apolipoprotein E (APOE) ε2 effects on cognitive decline. In non-Hispanic White (NHW) adults, APOE ε2 selectively protects men against decline. Among men, APOE ε2 was more protective than APOE ε3/ε3. In women, APOE ε2 was no more protective than APOE ε3/ε3. Among APOE ε2 carriers, men had slower decline than women. There were no sex-specific APOE ε2 effects in non-Hispanic Black (NHB) adults.

Abstract Lymphatic vessels are essential for preventing the accumulation of harmful components within peripheral tissues, including the artery wall. Various endogenous mechanisms maintain adequate lymphatic function throughout life, with platelets being essential for preserving lymphatic vessel integrity. However, since lymph lacks platelets, their impact on the lymphatic system has long been viewed as restricted to areas where lymphatics intersect with blood vessels. Nevertheless, platelets can also exert long range effects through the release of extracellular vesicles (EVs) upon activation. We observed that platelet EVs (PEVs) are present in lymph, a compartment to which they could transfer regulatory effects of platelets. Here, we report that PEVs in lymph exhibit a distinct signature enabling them to interact with lymphatic endothelial cells (LECs). In vitro experiments show that the internalization of PEVs by LECs maintains their functional integrity. Treatment with PEVs improves lymphatic contraction capacity in atherosclerosis-prone mice. We suggest that boosting lymphatic pumping with exogenous PEVs offers a novel therapeutic approach for chronic inflammatory diseases characterized by defective lymphatics.

New hydrothermal experiments in rapid-quench pressure vessels have been performed to investigate the effect of redox state on the serpentinization reaction. The experimental hydrogen fugacity (fH2) was controlled by monitoring the mobility of H2 in the reacting system (internal vs. external fH2 control). This was achieved by using either Au (H2 impermeable) or AgPd (H2 permeable) capsules and Ar pressurizing gas to control fH2. The experiments were performed with either San Carlos olivine powders or Åheim dunite chips. Water / rock mass ratios of 1–2, a total pressure of 50 MPa, and temperatures of 300 and 350 °C were investigated. Experimental durations of 30, 45, or ≈80 d were imposed. Serpentine production is observed in almost all experiments but is favored at 300 °C under external fH2 control. The serpentine–magnetite assemblage is observed in Au capsules (high fH2) at 300 °C, while the serpentine–hematite(–magnetite) is observed in AgPd capsules (low fH2). At 350 °C, less H2 is produced than at 300 °C and the serpentine–hematite(–magnetite) assemblage is present in both Au and AgPd capsules. Brucite is absent and this is interpreted to reflect both the initially oxidizing conditions and relatively low serpentine production in our experiments. Differences in product phase assemblages found in this study imply that natural serpentinization reaction mechanisms vary with redox conditions, and consequences for H2 production fluxes and rates can be expected. The high-fH2 (reduced) internally controlled experiments simulate low-permeability “closed” oceanic hydrothermal systems. The low-fH2 (oxidized) externally controlled experiments are analogous to “open” oceanic hydrothermal systems where serpentinization is driven by tectonically aided infiltration of an external fluid.

Abstract Cities concentrate problems that affect human well-being and biodiversity. Exploring the link between mental health and biodiversity can inform more holistic public health and urban planning. Here we examined associations between bird and tree species diversity estimates from eBird community science datasets and national forest inventories with self-rated mental health metrics from the Canadian Community Health Survey. We linked data across 36 Canadian Metropolitan Areas from 2007-2022 at a postal code level. After controlling for covariates, we found that bird and tree species diversity were significantly positively related to good self-reported mental health. Living in a postal code with bird diversity one standard deviation higher than the mean increased reporting of good mental health by 6.64%. Postal codes with tree species richness one standard deviation more than the mean increased reporting of good mental health by 5.36%. Our results suggest that supporting healthy urban ecosystems may also benefit human well-being.