McMaster University

In the light of the precursor of sex hormones, dietary fat may affect their levels. In the present meta‐analysis, we sought to compare the effects of low‐fat versus high‐fat diets on sex hormones and their metabolites in adults. Databases were searched up to June 2024 to identify randomized controlled trials comparing low‐fat diets (fat intake ≤30% of total energy) with high‐fat diets in relation to circulating sex hormone levels. A random‐effects meta‐analysis was performed, incorporating data from 11 trials with 888 participants. Studies were selected based on their comparison of low‐fat versus high‐fat diets and the measurement of sex hormone concentrations. The meta‐analysis found no significant differences in serum levels of various sex hormones between low‐fat and high‐fat diet groups. The hormones assessed included estradiol (95% CI, −7.71, 1.10), estrone (95% CI, −12.39, 24.76), sex hormone‐binding globulin (95% CI, −3.22, 0.70), dehydroepiandrosterone (95% CI, −0.38, 0.46), testosterone (95% CI, −14.48, 13.50), progesterone (95% CI, −2.82, 1.75), and androstenedione (95% CI, −0.54, 0.03). We found no significant effect of low‐fat diets on sex hormones compared with high‐fat diets. Our findings, however, were tempered by the small number of studies and low certainty of evidence.

Background Sexual concerns are reported by 43%–82.5% of peri- and post-menopausal women and negatively impact physical and emotional well-being. Despite the high prevalence and negative impact, treatment options are limited, particularly those which are non-pharmacological. Aim The primary objective of this pilot trial was to evaluate the effectiveness of a novel four-session individual Cognitive Behavioural Therapy protocol for improving sexual functioning (CBT-SC-Meno) during peri- and post-menopause. Secondary objectives included assessing body image, relationship satisfaction, and common menopause symptoms (eg, vasomotor), depression, anxiety, and self-reported health. Methods Participants (n = 32) were peri- or post-menopausal women experiencing primary sexual concerns and reporting a score of 26.55 or lower on the Female Sexual Function Index (FSFI), indicating impaired sexual functioning. Eligible participants were assigned to a waitlist control condition for 4 weeks, after which they were reassessed and then completed the CBT protocol. Outcomes Measures assessing sexual functioning, satisfaction, distress, and desire, as well as body image, relationship satisfaction, common menopause symptoms (eg, vasomotor), depression, anxiety, and self-reported health were completed at baseline, post-waitlist, and post-treatment. Treatment satisfaction was captured with the Client Satisfaction Questionnaire along with qualitative data. Results During the waitlist period, no significant changes were observed across measures, apart from the FSDQ concern subscale and GCS physical subscale. Following CBT-SC-Meno, participants experienced a significant improvement in overall sexual functioning (eg, desire, arousal, reduced pain, satisfaction), a decrease in symptoms of sexual distress, concern, and resistance, menopausal symptoms, symptoms of depression and anxiety, as well as improved body image, couple satisfaction, and overall health (P < 0.001). All participants endorsed high treatment satisfaction and indicated that treatment helped them better cope with their symptoms more effectively. Clinical Implications To our knowledge, this is the first study examining the effectiveness of a CBT protocol specifically designed to target sexual concerns experienced during peri- and post-menopause. Results suggest that CBT-SC-Meno leads to significant improvements in sexual functioning across several important sexual concern domains and related areas (eg, body image), in addition to several other commonly comorbid menopausal symptoms (eg, vasomotor), depression, anxiety, and self-reported overall health. Strengths and Limitations Although CBT-SC-Meno appears to be a promising treatment for sexual concerns, the sample was small and homogeneous. Conclusions This study provides preliminary evidence of CBT as a non-pharmacological treatment for peri- and post-menopausal women experiencing sexual concerns and offers the basis for a larger randomized clinical trial. Clinical trial registration Trial # NCT04922385 and Accessible at: https://clinicaltrials.gov/ct2/show/NCT04922385?term=NCT04922385&draw=2&rank=1

Geroscience is an emerging interdisciplinary field that explores the biological connections between aging and the development of chronic diseases, with the ultimate goal of identifying interventions to extend healthspan and delay age-related conditions. Recognizing the growing importance of this field, the Canadian Translational Geroscience Network (CTGN, geroscience.ca) was officially launched during a conference held in Montreal on September 5–6, 2024. Building on the momentum of successful Geroscience meetings in Toronto and Montreal in 2023, this milestone event marked a transformative step forward for geroscience in Canada. This event brought together key stakeholders, including the Canadian Frailty Network (CFN), the Canadian Institutes of Health Research Institute of Aging (CIHR-IA), the Réseau Québécois de Recherche sur le Vieillissement (RQRV), the Simone & Edouard Schouela RUISSS McGill Centre of Excellence for Sustainable Health of Seniors (Schouela CEDurable), the Division of Geriatric Medicine at McGill University, and the Department of Biochemistry at the University of Toronto. Additionally, a broad coalition of geriatricians, healthcare professionals, and researchers convened to discuss and advance the field of geroscience in Canada. The two-day conference focused on creating a multidisciplinary community to address the challenges of an aging population, emphasizing the importance of funding, national and international collaboration, and training the next generation of researchers and clinicians. Workshops and presentations showcased a range of innovative research, from cellular studies to clinical trials, aimed at understanding and treating age-related diseases. Key discussions highlighted the critical role of partnerships among research institutions, healthcare systems, and biotech companies in translating research findings into practical interventions. The CTGN's strategic objectives focus on expanding funding opportunities for geroscience, developing specialized training programs, and increasing membership to cultivate a diverse, multidisciplinary, and collaborative network. This network aims to include students, basic and clinical researchers, citizens, government entities, and organizations or professionals interested in advancing the geroscience field. With a clear roadmap for future growth, the CTGN aims to position Canada at the forefront of geroscience, fostering evidence-based innovation that improves the health and quality of life for aging populations.

Importance Post–cancer therapy kidney outcomes, including chronic kidney disease (CKD) and hypertension, are common in childhood cancer survivors (CCS). The incidence and timing of CKD and hypertension in CCS compared with other at-risk or general populations are unclear. Objective To determine the association of childhood cancer treatment with post–cancer therapy CKD or hypertension. Design, Setting, and Participants Population-based matched cohort study of children treated for cancer between April 1993 and March 2020 in Ontario, Canada, with follow-up until March 2021. The CCS (exposed) cohort included children (≤18 years) surviving cancer. Comparator cohorts were a hospitalization cohort (children who were hospitalized) and a general pediatric population (GP) cohort (all other Ontario children). Exclusion criteria were history of previous cancer, organ transplant, CKD, dialysis, or hypertension. Matching with each of the 2 comparator cohorts was performed separately and in a 1:4 ratio by age, sex, rural vs urban status, income quintile, index year, and presence of previous hospitalization. Data were analyzed from March 2021 to August 2024. Exposure Treatment for cancer. Main Outcomes and Measures The primary outcome was the composite of CKD or hypertension, defined by administrative health care diagnosis and procedure codes. Fine and Gray subdistribution hazard modeling, accounting for competing risks (death and new cancer diagnosis or relapse) and adjusting for cardiac disease, liver disease, and diabetes, was used to determine the association of cancer treatment with outcomes. Results There were 10 182 CCS (median [IQR] age at diagnosis, 7 [3-13] years; 5529 male [54.3%]; median [IQR] follow-up time, 8 [2-15] years) matched to 40 728 hospitalization cohort patients (median [IQR] age at diagnosis, 7 [2-12] years; 5529 male [weighted percentage, 54.3%]; median [IQR] follow-up time, 11 [6-18] years) and 8849 CCS (median [IQR] age at diagnosis, 5 [2-11] years; 4825 male [54.5%]; median [IQR] follow-up time, 7 [2-14] years) matched to 35 307 GP cohort individuals (median [IQR] age at diagnosis, 6 [2-11] years; 4825 male [weighted percentage, 54.5%]; median [IQR] follow-up time, 10 [5-16] years). Most frequent cancer types were leukemia (2948 patients [29.0%]), central nervous system neoplasms (2123 patients [20.9%]), and lymphoma (1583 patients [15.5%]). During observation, cumulative incidence of CKD or hypertension was 20.85% (95% CI, 18.75%-23.02%) in the CCS cohort vs 16.47% (95% CI, 15.21%-17.77%) in the hospitalization cohort and 19.24% (95% CI, 15.99%-22.73%) in the CCS cohort vs 8.05% (95% CI, 6.76%-9.49%) in the GP cohort. CCS were at increased risk of CKD or hypertension compared with the hospitalization cohort (adjusted hazard ratio, 2.00; 95% CI, 1.86-2.14; P < .001) and the GP cohort (adjusted hazard ratio, 4.71; 95% CI, 4.27-5.19; P < .001). Conclusions and Relevance In this population-based study, CCS were at increased risk for CKD and hypertension, which are associated with mortality, suggesting that early detection and treatment of these conditions in CCS may decrease late complications and mortality.

From October 8–13, 2023, a highly diverse group of scholars gathered at the 36th Ernst Strüngmann Forum in Frankfurt am Main, Germany, to advance conceptualizations of gender and sex, to align dialogue across disciplines, and to promote sound application in research, policy, medicine, and public health.

Abstract Given the proliferation of calls to consider sex and gender in biomedicine, it is critical to address how the two concepts, and the relationships between them, are being implemented in a research setting. This chapter considers how we might transcend a simple, binary female–male framing and embrace the idea of the entanglement of sex and gender. The ways that the terms sex and gender are typically used in biology and health research are considered, with a focus on the relationships between these constructs, and areas of coherence and disagreement in their conceptualization. Problems arise when sex and gender are principally operationalized in terms of a female–male binary, including not only the resulting exclusion of trans, nonbinary, and intersex individuals but also the inadequacy of a binary analytical framework to account for context, overlap, in-group heterogeneity, continuity, and similarity. Entanglement and interaction are compared and contrasted, three forms of scientifc engagement with these ideas are identifed, and the implications of intersectionality for the operationalization of sex and gender are considered. In the context of experimentation, an entanglement perspective on sex and gender is explored for what it might enable along with the challenges it presents. As researchers grapple with the incorporation of sex and gender in their work, these frameworks will require ongoing development and refnement, reduced reliance on the dominant binary female–male analytical framing, and a move to a contextual, mechanistic approach that better refects conceptual complexity, diverse

The identification of queuing status in traffic streams is a pivotal task with implications for various applications, such as level of service estimation and signal timing optimization. This study presents a comparative approach for binary classification of vehicles into queuing and non-queuing statuses using machine learning techniques based on vehicle headway anomalies. The proposed models leverage features from vehicle movement data at the stopline as input and queuing status as output. Four machine learning methods, the support vector machine, random forest, logistics regression, and Gaussian mixture model, are used and compared in the proposed headway anomaly detection framework. To validate the models, a simulation environment is constructed in VISSIM 4.3 and calibrated using real-world data. Results indicate that the random forest exhibits superior classification performance, showcasing its effectiveness as an ensemble approach. Notably, the resilience of these models is tested against the missing detection rate, with the random forest showing robust performance across different missing detection rate levels. Furthermore, feature importance analysis within the random forest model reveals “acceleration” and “headway” as significant predictors for classifying queuing status. The results advocate for the efficacy of the random forest model as a method for queuing status detection, indicating its utility for traffic analysis and the optimization of transportation network operations.

Indecisive behaviour can be catastrophic, leading to car crashes or stock market losses. Despite fruitful efforts across several decades to understand decision-making, there has been little research on what leads to indecision. Here we examined how indecisions arise under high-pressure deadlines. In our first experiment participants attempted to select a target by either reacting to a stimulus or guessing, when acting under a high pressure time constraint. We found that participants were suboptimal, displaying a below chance win percentage due to an excessive number of indecisions. Computational modelling suggested that participants were excessively indecisive because they failed to account for a time delay and temporal uncertainty when switching from reacting to guessing, a phenomenon previously unreported in the literature. In a follow-up experiment we pro- vide direct evidence for a functionally relevant time delay and temporal uncertainty when switching from reacting to guessing. Collectively, our results indicate that participants failed to account for a time delay and temporal uncertainty associated with switching from reacting to guessing, leading to suboptimal and indecisive behaviour.

Background For many diseases, early diagnosis and treatment are more cost-effective, reduce community spread of infectious diseases and result in better patient outcomes. However, healthcare-seeking and diagnoses for several diseases are unnecessarily delayed. For example, in 2022, 3 million and 5.6 million people living with tuberculosis (TB) and HIV, respectively, were undiagnosed. Many patients never access appropriate testing, remain undiagnosed after testing or drop out shortly after treatment initiation. This underscores challenges in accessing healthcare for many individuals. Understanding healthcare-seeking obstacles can expose bottlenecks in healthcare delivery and promote equity of access. We aimed to synthesise methodologies used to portray healthcare-seeking trajectories and provide a conceptual framework for patient journey analyses. Design/methods We conducted a literature search using keywords related to “patient/care healthcare-seeking/journey/pathway analysis” AND “TB” OR “infectious/pulmonary diseases” in PubMed, CINAHL, Web of Science and Global Health (OVID). From a preliminary scoping search and expert consultation, we developed a conceptual framework and honed the key data points necessary to understand patients’ healthcare-seeking journeys, which then served as our inclusion criteria for the subsequent expanded review. Retained papers included at least three of these data points. Results Our conceptual framework included five data points and seven related indicators that contribute to understanding patients’ experiences during healthcare-seeking. We retained 66 studies that met our eligibility criteria. Most studies (56.3%) were in Central and Southeast Asia, explored TB healthcare-seeking experiences (76.6%), were quantitative (67.2%), used in-depth, semistructured or structured questionnaires for data collection (73.4%). Healthcare-seeking journeys were explored, measured and portrayed in different ways, with no consistency in included information. Conclusions We synthesised various methodologies in exploring patient healthcare-seeking journeys and found crucial data points necessary to understand challenges patients encounter when interacting with health systems and offer insights to researchers and healthcare practitioners. Our framework proposes a standardised approach to patient journey research.

Objectives Computer‐aided diagnosis (CADx) is anticipated to enhance the prediction of colorectal polyp histology. This study aims to compare the diagnostic accuracy of CADx in the optical diagnosis of colorectal polyps, evaluating its performance against that of both experienced and inexperienced endoscopists. Methods The protocol of this study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (ID: CRD42024585097). Three electronic databases including MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched in September 2024. A bivariate random effects model was employed. The primary outcome was the comparison of sensitivity and specificity between CADx and experienced endoscopists; the secondary outcome was the comparison between CADx and inexperienced endoscopists. Results Twenty‐one studies involving 5477 polyps were included. The pooled sensitivities of CADx and experienced endoscopists were 0.87 (95% confidence interval [CI] 0.82–0.91) and 0.88 (95% CI 0.83–0.91), respectively ( P = 0.93). The pooled specificities of CADx and experienced endoscopists were 0.85 (95% CI 0.78–0.90) and 0.87 (95% CI 0.82–0.92), respectively ( P = 0.53). In nine studies comparing CADx with inexperienced endoscopists, the pooled sensitivities were 0.88 (95% CI 0.82–0.92) for CADx and 0.85 (95% CI 0.78–0.90) for inexperienced endoscopists ( P = 0.46). The pooled specificities were 0.84 (95% CI 0.78–0.88) for CADx and 0.77 (95% CI 0.70–0.83) for inexperienced endoscopists ( P = 0.16). Conclusion Computer‐aided diagnosis does not demonstrate superior diagnostic accuracy in optical diagnosis of colorectal polyps compared to endoscopists, regardless of their experience level.

We establish the spacetime Penrose inequality in spherical symmetry in spacetime dimensions n + 1 ≥ 3 with charge and cosmological constant from the initial data perspective. We also show that this result extends to the Gauss-Bonnet theory of gravity.

Current models of rhythm perception propose that humans track musical beats using the phase, period, and amplitude of sound patterns. However, a growing body of evidence suggests that pitch can also influence the perceived timing of auditory signals. In the present study, we conducted two experiments to investigate whether pitch affects the phase and period of sensorimotor synchronization. To do so, we asked participants to synchronize with a repeating tone, whose pitch on each trial was drawn from one of six different octaves (110–3520 Hz). In Experiment 1, we observed U-shaped patterns in both mean asynchrony and continuation tapping rates, with participants tapping latest and slowest when synchronizing to low and extremely high (above 2000 Hz) pitches, and tapping earliest and fastest to moderately high pitches. In Experiment 2, we found that extremely high pitches still produced slower timing than moderately high pitches when participants were exposed to an exclusively high-pitched context. Based on our results, we advocate for the incorporation of pitch into models of rhythm perception and discuss possible origins of these effects.

A kinetic model coupling prebiotically plausible synthesis of enantioenriched proteinogenic amino acids with catalytic peptide ligation leads to an autocatalytic network that may exhibit symmetry breaking and chiral amplification, providing a feasible route to the emergence of biological homochirality. We show that symmetry breaking leading to chiral amplification can occur in two ways: a constructive mechanism in which dimers catalyze the synthesis of monomers of the same enantiomer, and a destructive mechanism in which dimers catalyze the breakdown of monomers of the opposite enantiomer.

INTRODUCTION Oxidative stress (OS) is implicated in dementia. While elevated peripheral OS biomarkers were observed in vascular mild cognitive impairment (vMCI), the role of central antioxidants remains unclear. We assessed levels of the major brain antioxidant glutathione (GSH) in vMCI compared to cognitively normal coronary artery disease (CAD) controls (CN). METHODS In vivo tissue‐corrected GSH in the anterior cingulate cortex (ACC) and occipital cortex (OC) were quantified in persons with vMCI and CN using MEscher–GArwood Point RESolved magnetic resonance Spectroscopy. RESULTS Among participants (vMCI, n = 22, age [mean ± SD] = 67.4 ± 7.3; CN, n = 21, age = 66.7 ± 7.8), ACC‐GSH (i.u. ± SD) was higher in vMCI (4.42 ± 0.59) versus CN (3.72 ± 1.01) (Z = −2.5, p = .01), even after controlling for age and sex (B [SE] = 0.74 [0.26], p = .007). Increased ACC‐GSH correlated with poorer executive function (EF) (B [SE] = −0.31 [0.14], p = .04). OC‐GSH showed no effect. DISCUSSION Higher ACC‐GSH in vMCI may reflect a compensatory response to OS. ACC‐GSH was negatively correlated with EF, suggesting a linkage between regional brain antioxidants and disease‐relevant cognitive domains. Highlights Brain GSH was measured in vascular MCI and matched controls using MEGA‐PRESS. In contrast to GSH deficits in AD, anterior cingulate GSH was elevated in vMCI. Brain GSH was correlated with disease‐relevant cognitive domains in vMCI. The GSH antioxidant system may be etiologically implicated in vMCI.

Background The LoDoCo2 (Low‐Dose Colchicine 2) trial showed that colchicine reduced the risk for cardiovascular events in patients with chronic coronary syndrome. Current guidelines recommend colchicine use in selected high‐risk patients. The aim of this secondary analysis was to explore the relative and absolute benefits of colchicine according to baseline risk. Methods The LoDoCo2 trial randomized 5522 patients to colchicine 0.5 mg or placebo. The primary end point was a composite of cardiovascular death, spontaneous myocardial infarction, ischemic stroke, or ischemia‐driven coronary revascularization. First, a LoDoCo2 risk score was developed by Cox regression to identify high‐risk features for the primary end point. Second, the Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention was applied to explore robustness of findings. Results In the LoDoCo2 risk score, high‐risk features were age ≥75, diabetes, and current smoker. In high‐risk (≥1 high‐risk feature), compared with low‐risk (0 high‐risk features) patients, colchicine was associated with consistent relative (high risk: hazard ratio [HR], 0.72 [95% CI, 0.56–0.94] versus low risk: HR, 0.67 [95% CI, 0.52–0.88]; P for interaction=0.73) and absolute benefits (high risk: HR, −1.33 [95% CI, −2.38 to −0.27] versus low risk: HR, −0.93 [95% CI −1.57 to −0.30] events per 100 person‐years). Using the Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention, consistent relative and absolute benefits were found in high‐, intermediate‐, and low‐risk patients. Conclusions In patients with chronic coronary syndrome, the relative and absolute benefits of colchicine were consistent in those at high, intermediate, and low risk for cardiovascular events. These findings support the use of colchicine across the spectrum of baseline risk. Registration URL: https://www.anzctr.org.au ; Unique identifier: 12614000093684.

Objectives Non-suicidal self-injury (NSSI) is a common behaviour in youth with mental disorder and in the general population. While NSSI is an important predictor of suicide attempts, not all youth with NSSI experience this outcome. The objective of this study is to report on the overlap between NSSI and suicidal ideation or attempt among Canadian youth self-reporting these behaviours in the general population to define a group of youth who engage in NSSI alone. This group of youth may represent a unique clinical phenotype. Methods We used data from 14–17 year olds ( N = 2,576) from the 2014 Ontario Child Health Study, a province-wide, cross-sectional, epidemiologic study of child health and mental disorder. Based on their responses to questions about past year experiences of suicidal thoughts and behaviours including NSSI, 6 mutually exclusive groups were created reflecting their differing profiles of suicidal thoughts and behaviours. These groups were compared to each other on socio-demographic and symptom characteristics. Results A total of 9.2% of youth reported NSSI, and half of these youth endorsed NSSI alone (without suicidal ideation or attempts). Both groups had significantly more females. Compared to other groups of youth endorsing suicidal thoughts and behaviours, the NSSI alone group had lower symptoms of mental disorder in all domains except for social anxiety symptoms. They also had the lowest perceived need for help of all groups. Conclusions About half of youth who self-harm do so without suicidal intent, and some for as long as 1 year during adolescence. Further prospective study of youth with NSSI alone is needed, to determine symptom stability as well as incident more risky suicidal behaviour before recommendations regarding the appropriateness of minimal medical or psychological intervention for youth who engage in this behaviour can be considered. There also are important sex differences in NSSI that deserve additional prospective study.