Trainees' perspectives and recommendations for catalyzing the next generation of NeuroAI researchers.

At this critical juncture in the development of NeuroAI, we outline challenges and training needs of junior researchers working across AI and neuroscience. We also provide advice and resources to help trainees plan their NeuroAI careers.

Patent Foramen Ovale Closure in Older Patients With Stroke: Patient Selection for Trial Feasibility.

Background And Objectives: Whether patent foramen ovale (PFO) closure benefits older patients with PFO and cryptogenic stroke is unknown because randomized controlled trials (RCTs) have predominantly enrolled patients younger than 60 years of age. Our objective was to estimate anticipated effects of PFO closure in older patients to predict the numbers needed to plan an RCT.

Methods: Effectiveness estimates are derived from major observational studies (Risk of Paradoxical Embolism [RoPE] Study and Oxford Vascular Study, together referred to as the "RoPE-Ox" database) and all 6 major RCTs (Systematic, Collaborative, PFO Closure Evaluation [SCOPE] Consortium).

Simple versus Radical Hysterectomy in Women with Low-Risk Cervical Cancer.

Background: Retrospective data suggest that the incidence of parametrial infiltration is low in patients with early-stage low-risk cervical cancer, which raises questions regarding the need for radical hysterectomy in these patients. However, data from large, randomized trials comparing outcomes of radical and simple hysterectomy are lacking.

Methods: We conducted a multicenter, randomized, noninferiority trial comparing radical hysterectomy with simple hysterectomy including lymph-node assessment in patients with low-risk cervical cancer (lesions of ≤2 cm with limited stromal invasion).

Chemical and biological characterization of vaccine adjuvant QS-21 produced via plant cell culture.

Many vaccines, including those using recombinant antigen subunits, rely on adjuvant(s) to enhance the efficacy of the host immune responses. Among the few adjuvants clinically approved, QS-21, a saponin-based immunomodulatory molecule isolated from the tree bark of (QS) is used in complex formulations in approved effective vaccines. High demand of the QS raw material as well as manufacturing scalability limitation has been barriers here.

Competency-based cardiac imaging for patient-centred care. A statement of the European Society of Cardiology (ESC). With the contribution of the European Association of Cardiovascular Imaging (EACVI), and the support of the Association of Cardiovascular Nursing & Allied Professions (ACNAP), the Association for Acute CardioVascular Care (ACVC), the European Association of Preventive Cardiology (EAPC), the European Association of Percutaneous Cardiovascular Interventions (EAPCI), the European Heart Rhythm Association (EHRA), and the Heart Failure Association (HFA) of the ESC.

Imaging plays an integral role in all aspects of managing heart disease and cardiac imaging is a core competency of cardiologists. The adequate delivery of cardiac imaging services requires expertise in both imaging methodology-with specific adaptations to imaging of the heart-as well as intricate knowledge of heart disease. The European Society of Cardiology (ESC) and the European Association of Cardiovascular Imaging have developed and implemented a successful education and certification programme for all cardiac imaging modalities.

Structural journey of an insecticidal protein against western corn rootworm.

The broad adoption of transgenic crops has revolutionized agriculture. However, resistance to insecticidal proteins by agricultural pests poses a continuous challenge to maintaining crop productivity and new proteins are urgently needed to replace those utilized for existing transgenic traits. We identified an insecticidal membrane attack complex/perforin (MACPF) protein, Mpf2Ba1, with strong activity against the devastating coleopteran pest western corn rootworm (WCR) and a novel site of action.

Inhibiting membrane rupture with NINJ1 antibodies limits tissue injury.

Plasma membrane rupture (PMR) in dying cells undergoing pyroptosis or apoptosis requires the cell-surface protein NINJ1. PMR releases pro-inflammatory cytoplasmic molecules, collectively called damage-associated molecular patterns (DAMPs), that activate immune cells. Therefore, inhibiting NINJ1 and PMR may limit the inflammation that is associated with excessive cell death.

A practical approach to curate clonal hematopoiesis of indeterminate potential in human genetic data sets.

Clonal hematopoiesis of indeterminate potential (CHIP) is a common form of age-related somatic mosaicism that is associated with significant morbidity and mortality. CHIP mutations can be identified in peripheral blood samples that are sequenced using approaches that cover the whole genome, the whole exome, or targeted genetic regions; however, differentiating true CHIP mutations from sequencing artifacts and germ line variants is a considerable bioinformatic challenge. We present a stepwise method that combines filtering based on sequencing metrics, variant annotation, and population-based associations to increase the accuracy of CHIP calls.

The Acute Effects of Milk Consumption on Systemic Inflammation after Combined Resistance and Plyometric Exercise in Young Adult Females.

High-intensity/impact exercise elicits a transient increase in inflammatory biomarkers. Consuming nutrient-dense wholefoods, like milk, following exercise may modulate post-exercise inflammation and aid recovery. We examined the effect of post-exercise skim milk consumption (versus an isoenergetic, isovolumetric carbohydrate [CHO] drink) on acute exercise-induced inflammation in untrained females.

The Influence of Increased Dairy Product Consumption, as Part of a Lifestyle Modification Intervention, on Diet Quality and Eating Patterns in Female Adolescents with Overweight/Obesity.

Our study examined how increased dairy consumption versus habitually low dairy consumption, against a background of healthy eating (and exercise), influenced diet quality, nutrient intake, and snacking in Canadian female adolescents (14.8 ± 2.2 years) with overweight/obesity (OW/OB).

A Tale of Two Cities: Unpacking the Success and Failure of School Street Interventions in Two Canadian Cities.

One innovative strategy to support child-friendly cities is street-based interventions that provide safe, vehicle-free spaces for children to play and move about freely. School streets are one such innovation involving closing streets around elementary schools to vehicular traffic to improve children's safety as they come and go from school while providing opportunities for children to play and socialize on the street. Launching these initiatives in communities dominated by automobiles is enormously challenging and little is known about why these interventions are successfully launched in some places but not others.

Duplex sequencing identifies genomic features that determine susceptibility to benzo(a)pyrene-induced in vivo mutations.

Exposure to environmental mutagens increases the risk of cancer and genetic disorders. We used Duplex Sequencing (DS), a high-accuracy error-corrected sequencing technology, to analyze mutation induction across twenty 2.4 kb intergenic and genic targets in the bone marrow of MutaMouse males exposed to benzo(a)pyrene (BaP), a widespread environmental pollutant.

Rare coding variants in 35 genes associate with circulating lipid levels-A multi-ancestry analysis of 170,000 exomes.

Large-scale gene sequencing studies for complex traits have the potential to identify causal genes with therapeutic implications. We performed gene-based association testing of blood lipid levels with rare (minor allele frequency < 1%) predicted damaging coding variation by using sequence data from >170,000 individuals from multiple ancestries: 97,493 European, 30,025 South Asian, 16,507 African, 16,440 Hispanic/Latino, 10,420 East Asian, and 1,182 Samoan. We identified 35 genes associated with circulating lipid levels; some of these genes have not been previously associated with lipid levels when using rare coding variation from population-based samples.

Health Economic Evaluations of Hip and Knee Interventions in Orthopaedic Sports Medicine: A Systematic Review and Quality Assessment.

Background: The economic burden of musculoskeletal diseases is substantial and growing. Economic evaluations compare costs and health benefits of interventions simultaneously to help inform value-based care; thus, it is crucial to ensure that studies are using appropriate methodology to provide valid evidence on the cost-effectiveness of interventions. This is particularly the case in orthopaedic sports medicine, where several interventions of varying costs are available to treat common hip and knee conditions.

Longitudinal Narrative Analysis of Parent Experiences During Graded Exposure Treatment for Children With Chronic Pain.

Objectives: Parents have a vital influence over their child's chronic pain treatment and management. Graded exposure in vivo treatment (GET) is emerging as a promising intervention for youth with chronic pain. Yet, little is known about how parents perceive GET and its impact on their child's pain condition.

A Novel Endovascular Therapy for CSF Hypotension Secondary to CSF-Venous Fistulas.

We report a consecutive case series of patients who underwent transvenous embolization of the paraspinal vein, which was draining the CSF-venous fistula, for treatment of spontaneous intracranial hypotension. These are the first-ever reported cases of this treatment for CSF-venous fistulas. All patients underwent spinal venography following catheterization of the azygous vein and then selective catheterization of the paraspinal vein followed by embolization of the vein with Onyx.

Using a simulation centre to evaluate preliminary acceptability and impact of an artificial intelligence-powered clinical decision support system for depression treatment on the physician-patient interaction.

Background: Recently, artificial intelligence-powered devices have been put forward as potentially powerful tools for the improvement of mental healthcare. An important question is how these devices impact the physician-patient interaction.

Aims: Aifred is an artificial intelligence-powered clinical decision support system (CDSS) for the treatment of major depression.

Thromboprophylaxis with Rivaroxaban in Acutely Ill Medical Patients with Renal Impairment: Insights from the MAGELLAN and MARINER Trials.

Patients with renal impairment are at higher risk of thrombosis and bleeding than those with normal renal function. The optimal rivaroxaban dose for thromboprophylaxis in acutely ill medical patients with renal impairment is unknown. MARINER and MAGELLAN were multicenter, randomized clinical trials of rivaroxaban in acutely ill medical patients.

, a Novel Transcription Factor and a Coregulator of Nuclear Factor B p65: Single Nucleotide Polymorphism and Estrogen Dependence.

T-cell leukemia 1A () single-nucleotide polymorphisms (SNPs) have been associated with aromatase inhibitor-induced musculoskeletal adverse events. We previously demonstrated that TCL1A is inducible by estradiol (E) and plays a critical role in the regulation of cytokines, chemokines, and Toll-like receptors in a SNP genotype and estrogen-dependent fashion. Furthermore, SNP-dependent expression phenotypes can be "reversed" by exposure to selective estrogen receptor modulators such as 4-hydroxytamoxifen (4OH-TAM).

Single-Nucleotide Polymorphisms and Estrogen-Mediated Toll-Like Receptor-MYD88-Dependent Nuclear Factor-B Activation: Single-Nucleotide Polymorphism- and Selective Estrogen Receptor Modulator-Dependent Modification of Inflammation and Immune Response.

In a previous genome-wide association study (GWAS) for musculoskeletal adverse events during aromatase inhibitor therapy for breast cancer, we reported that single nucleotide polymorphisms (SNPs) near the gene were associated with this adverse drug reaction. Functional genomic studies showed that TCL1A expression was induced by estradiol, but only in cells with the variant sequence for the top GWAS SNP (rs11849538), a SNP that created a functional estrogen response element. In addition, genotype influenced the downstream expression of a series of cytokines and chemokines and had a striking effect on nuclear factor B (NF-B) transcriptional activity.

Estrogen, SNP-Dependent Chemokine Expression and Selective Estrogen Receptor Modulator Regulation.

We previously reported, on the basis of a genome-wide association study for aromatase inhibitor-induced musculoskeletal symptoms, that single-nucleotide polymorphisms (SNPs) near the T-cell leukemia/lymphoma 1A (TCL1A) gene were associated with aromatase inhibitor-induced musculoskeletal pain and with estradiol (E2)-induced TCL1A expression. Furthermore, variation in TCL1A expression influenced the downstream expression of proinflammatory cytokines and cytokine receptors. Specifically, the top hit genome-wide association study SNP, rs11849538, created a functional estrogen response element (ERE) that displayed estrogen receptor (ER) binding and increased E2 induction of TCL1A expression only for the variant SNP genotype.

Aromatase inhibitor-associated bone fractures: a case-cohort GWAS and functional genomics.

Bone fractures are a major consequence of osteoporosis. There is a direct relationship between serum estrogen concentrations and osteoporosis risk. Aromatase inhibitors (AIs) greatly decrease serum estrogen levels in postmenopausal women, and increased incidence of fractures is a side effect of AI therapy.