Search

The concept of biological sex guides research, clinical practice, science funding policy, and contemporary political discourse. Despite some substantive differences, all existing candidate philosophical accounts of sex assume its legitimacy as a biological concept. Here, we challenge this view. We argue against realism about biological sex, and that eliminating biological sex from large swaths of biological theory and practice may be preferable compared to conventionalist or fictionalist anti-realisms. There are serious social and epistemic costs to using “biological sex” in place of more specific alternatives. Because of this, biologists and philosophers of science should consider eliminativism about the concept of biological sex. Biological sex eliminativism is worth taking seriously, and it can play important roles in philosophical debate and biological practice, even for those who remain skeptical. The methodological consequences of biological sex eliminativism are compatible with best practices for inquiry in the biological and biomedical sciences, with inclusive approaches to the study of sex and gender, and with feminist philosophical and methodological recommendations. Taking eliminativism seriously reveals important disagreement about the work that a concept of biological sex should do, and imposes a contrastive burden on would-be rivals. [ABSTRACT FROM AUTHOR]

Background: The worldwide population is ageing and self-arm can be prevented with many techniques. Among them coercive measure consisting of physical restraint (PR) is one of the techniques. This study aims to assess the effects of the biological sex on the long-term survival after PR in geriatric patients during the initial emergency department (ED) visit. Methods: This retrospective study included patients between November 2019 to March 2021. All consecutive hospitalized patients after emergency department visit older than 75 years with PR were included. The population was compared according to the biological sex. One-year all-cause mortality was plotted with the Kaplan-Meier curve. Hazard ratios (HRs) for 1-year mortality were calculated using a Cox proportional hazards regression model. Mortality was monitored over a 3-year period. Results: PR was used in 149 patients representing 4.6% of 3210 hospitalized patients older than 75 years after ED visit. Women represented 52% of the study population. Compared to men, women were older [median (IQR) age 89 (85–93) vs. 85 (81–90) years, P = 0.002]. Women more often presented dementia (93 vs. 80%, P = 0.031). Both sexes presented the same limited independence. All-cause mortality was significantly lower for women than men after one year (25 vs. 51%, respectively, P = < 0.001). Likewise, adjusted HR of 1-year all-cause mortality was higher in men [a HR 3.4 (95% confidence interval 1.7–7.1), P < 0.001]. Conclusion: This study suggested that the use of physical restraint in older adults was a more related factor of mortality in men than women. Women were older with lower expectancy life but PR use seemed to be a sign of global health decline in men. Further prospective studies are needed to assess if mortality after PR use is a cause or a consequence of a global health decline. [ABSTRACT FROM AUTHOR]

Cancer cachexia affects up to 80% of patients with cancer and results in reduced quality of life and survival. We previously demonstrated that the transcriptional repressor Forkhead box P1 (FoxP1) is upregulated in the skeletal muscle of cachectic mice and people with cancer, and when overexpressed in skeletal muscle, it is sufficient to induce pathological features characteristic of cachexia. However, the role of myofiber-derived FoxP1 in both normal muscle physiology and cancer-induced muscle wasting remains largely unexplored. To address this gap, we generated a conditional mouse line with myofiber‐specific ablation of FoxP1 (FoxP1SkmKO) and found that in cancer-free mice, deletion of FoxP1 in skeletal myofibers resulted in increased myofiber size in both males and females, with a significant increase in muscle mass in males. In response to murine KPC pancreatic tumor burden, we found that myofiber-derived FoxP1 mediates cancer-induced muscle wasting and diaphragm muscle weakness in male but not female mice. In summary, our findings identify myofiber-specific FoxP1 as a negative regulator of skeletal muscle with sex-specific differences in the context of cancer. NEW & NOTEWORTHY: Here we identify myofiber-derived FoxP1 as a negative regulator of skeletal muscle with sex-specific effects in cancer. Under cancer-free conditions, FoxP1 knockout increased myofiber size in male and female mice. However, in response to pancreatic cancer, FoxP1 myofiber-specific deletion attenuated muscle wasting and weakness in males but not females. This highlights the need to consider sexual dimorphism in cancer-induced muscle pathologies and provides evidence suggesting that targeting FoxP1 could help mitigate these effects in males. [ABSTRACT FROM AUTHOR]

Vascular smooth muscle cell (SMC) relaxation by guanylyl cyclases (GCs) and cGMP is mediated by NO and its receptor soluble GC (sGC) or natriuretic peptides (NPs) ANP/BNP and CNP with the receptors GC-A and GC-B, respectively. It is commonly accepted that cultured SMCs differ from those in intact vessels. Nevertheless, cell culture often remains the first step for signaling investigations and drug testing. Previously, we showed that even popular reference genes changed dramatically after SMC isolation from aorta. Regarding NP receptors, a substantial amount of data relies on cell culture. We hypothesize that the NP/cGMP system in intact aortic tunica media differs from isolated and cultured aortic SMCs. Therefore, we studied isolation and culturing effects on the expression of NP receptors GC-A, GC-B, and NP clearance receptor (NPRC) compared to sGC. We investigated intact tunica media and primary SMCs from the longitudinal halves of the same rat aorta. GC activity was monitored by cyclic guanosine monophosphate (cGMP). In addition, we hypothesize that there are sex-dependent differences in the NP/cGMP cascade in both intact tissue and cultured cells. We, therefore, analyzed a male and female cohort. Expression was quantified by RT-qPCR comparing aortic media and SMCs with our recently validated reference gene (RG) small nuclear ribonucleoprotein 2 (U2). Only GC-A was stably expressed. In intact media, GC-A exceeded GC-B and NPRC. However, GC-B, NPRC, and sGC were dramatically upregulated in cultured SMCs of the same aortae different from the stable GC-A. The expression was mirrored by NP-induced GC activity. In cultured cells, changes in GC activity were delayed compared to receptor expression. Minor differences between both sexes could also be revealed. Thus, isolation and culture fundamentally alter the cGMP system in vascular SMCs with potential impact on drug testing and scRNAseq. Especially, the dramatic increase in the clearance receptor NPRC in culture might distort all physiological ANP, BNP, and CNP effects. [ABSTRACT FROM AUTHOR]

In this study, Chinese and Swedish employment officers' assessments of physically impaired people and their ability to find jobs are compared. The study is qualitative, and data were collected through semi-structured interviews. The respondents were ten employment officers working full time. The results show that several employment officers in both contexts are skeptical that disabled people will be able to find work, and highlight similar obstacles to entering the labor market related to individual and societal conditions. The results show that, unlike Swedish employment officers, who highlight both types of obstacles, Chinese employment officers consider barriers related to the individual to be most important. The results also show that, compared to their Swedish colleagues, Chinese employment officers view gender and sex as more critical obstacles. The article argues that the results reveal different conceptions of disability and gender or sex that can be linked to the two contexts' welfare models. Points of interest: Previous studies have rarely examined whether employment barriers for disabled people can be related to the functioning of the employment services. This article compares assessments made by employment officers in China and Sweden of disabled people and their ability to find jobs. This article reveals that employment officers in both countries to some extent negatively assess the employment prospects of women and disabled people, and it is argued that under some circumstances the employment services can function as a barrier for disabled people to get a job. This article shows that employment officers' assessments differ depending on their perceptions of the applicants' disability and sex, as well as if the officer works in Sweden or in China. This article argues that the employment officers' expectations of disabled peoples' ability to work are in line with the overarching goals of the welfare in the two countries. [ABSTRACT FROM AUTHOR]

Vaccine-mediated protection and susceptibility to Streptococcus pneumoniae (pneumococcus) infections are influenced by biological sex. The incidence of invasive pneumococcal disease remains higher in males compared to females even after the introduction of the pneumococcal conjugate vaccine. However, sex-based differences in the immune response to this conjugate vaccine remain unexplored. To investigate those differences, we vaccinated adult male and female mice with pneumococcal conjugate vaccine and assessed cellular and humoral immune responses. Compared to females, male mice displayed lower levels of T follicular helper cells, germinal center B cells, and plasmablasts, which are all required for antibody production following vaccination. This was linked to lower IgG and IgM levels against pneumococci and lower isotype switching to IgG3 in vaccinated males. Due to lower antibody levels, sera of vaccinated male mice had lower efficacy in several anti-pneumococcal functions, including neutralization of bacterial binding to pulmonary epithelial cells as well as direct cytotoxicity against S. pneumoniae. Importantly, while the vaccine was highly protective in females, vaccinated males succumbed to infection more readily and were more susceptible to both lung-localized infection and systemic spread following S. pneumoniae challenge. These findings identify sex-based differences in immune responses to pneumococcal conjugate vaccine that can inform future vaccine strategies. [ABSTRACT FROM AUTHOR]

Abstract Background The worldwide population is ageing and self-arm can be prevented with many techniques. Among them coercive measure consisting of physical restraint (PR) is one of the techniques. This study aims to assess the effects of the biological sex on the long-term survival after PR in geriatric patients during the initial emergency department (ED) visit. Methods This retrospective study included patients between November 2019 to March 2021. All consecutive hospitalized patients after emergency department visit older than 75 years with PR were included. The population was compared according to the biological sex. One-year all-cause mortality was plotted with the Kaplan-Meier curve. Hazard ratios (HRs) for 1-year mortality were calculated using a Cox proportional hazards regression model. Mortality was monitored over a 3-year period. Results PR was used in 149 patients representing 4.6% of 3210 hospitalized patients older than 75 years after ED visit. Women represented 52% of the study population. Compared to men, women were older [median (IQR) age 89 (85–93) vs. 85 (81–90) years, P = 0.002]. Women more often presented dementia (93 vs. 80%, P = 0.031). Both sexes presented the same limited independence. All-cause mortality was significantly lower for women than men after one year (25 vs. 51%, respectively, P =

Abstract Objective Comorbidity of epilepsy and autism in tuberous sclerosis complex 2 (TSC2) is very frequent, but the link between these conditions is still poorly understood. To study neurological problems related to autism, the scientific community has been using an animal model of TSC2, Tsc2+/− mice. However, it is still unknown whether this model has the propensity to exhibit increased seizure susceptibility. Further, the importance of sex and/or the circadian cycle in this biological process has never been addressed. This research aimed to determine whether male and female Tsc2+/− mice have altered seizure susceptibility at light and dark phases. Methods We assessed seizure susceptibility and progression in a Tsc2+/− mouse model using the chemical convulsant kainic acid (KA), a potent agonist of the AMPA/kainate class of glutamate receptors. Both male and female animals at adult age were evaluated during non‐active and active periods. Seizure severity was determined by integrating individual scores per mouse according to a modified Racine scale. Locomotor behavior was monitored during control and after KA administration. Results We found increased seizure susceptibility in Tsc2+/− mice with a significant influence of sex and circadian cycle on seizure onset, progression, and behavioral outcomes. While, compared to controls, Tsc2+/− males overall exhibited higher susceptibility independently of circadian cycle, Tsc2+/− females were more susceptible during the dark and post‐ovulatory phase. Interestingly, sexual dimorphisms related to KA susceptibility were always reported during light phase independently of the genetic background, with females being the most vulnerable. Significance The enhanced susceptibility in the Tsc2 mouse model suggests that other neurological alterations, beside brain lesions, may be involved in seizure occurrence for TSC. Importantly, our work highlighted the importance of considering biological sex and circadian cycle for further studies of TSC‐related epilepsy research. Plain Language Summary Tuberous sclerosis complex (TSC) is a rare genetic disorder. It causes brain lesions and is linked to epilepsy, intellectual disability, and autism. We wanted to investigate epilepsy in this model. We found that these mice have more induced seizures than control animals. Our results show that these mice can be used in future epilepsy research for this disorder. We also found that sex and time of day can influence the results. This must be considered in this type of research.

U.S. females live longer than males due to a range of social, psychological, behavioral, and health factors. Prior research has underscored unhealthy behaviors as particularly risky for males and lower socioeconomic status as a risk factor for females in shaping sex differences in adult mortality. But this research has largely examined mortality during mid- and older-adulthood, with most deaths occurring at older ages. Our study focuses on sex differences in mortality among a cohort of U.S. adolescents followed into adulthood, ages 12–46 (N = 18,921). We employ Cox proportional hazard models and data from the National Longitudinal Study of Adolescent to Adult Health (Add Health), which was recently linked to mortality records through December of 2021. The hazard of dying is much greater (HR = 1.69; p <.001) for male compared to female adolescents and young adults, with larger disparities for external compared to internal causes of death. Sex differences in mortality are reduced but persist when controlling for childhood experiences, health behaviors, risky behaviors, and social ties. The relatively poor mental and physical health of females suppresses the differences; that is, sex differences in mortality would be even larger were it not for the poorer mental and physical health of young females compared with males. The findings point to risk factors that if improved could reduce mortality for both U.S. males and females, while reducing sex differences in mortality among younger adults. Such improvements could increase life expectancy of the U.S. population and reduce mortality and sex differences at older ages. [ABSTRACT FROM AUTHOR]

Physical activity has been demonstrated to improve cognitive function, thereby preventing/slowing neurodegenerative diseases (NDs). Biological responses to physical activity and vulnerabilities to NDs are emerging to be gender-related. Herein, known ND-associated markers (β-amyloid, tau, α-synuclein), main sex steroid hormones, antioxidant responses, and key gene transcription modulators were evaluated in the blood of physically active and sedentary women and men. In our hands, females presented higher basal erythrocytes β-amyloid and α-synuclein amounts than males. Regular physical activity was able to significantly reduce the erythrocyte content of β-amyloid in females and the tau levels in males, suggesting that these differences may be mediated by organizational actions of sex steroid hormones during development. Furthermore, despite a comparable plasma antioxidant capability (AOC) between males and females, in the latter group, physical activity significantly enhances AOC versus peroxynitrite radicals only. Finally, regular physical activity modulated the levels of transcription factor Nrf2 in erythrocytes, as well as the plasma concentration of the microRNA miR-195 and miR-153, suggesting the promotion of antioxidant/autophagic processes associated with ND-related proteins. Overall, these results could shed light on how cerebral adaptations to physical activity differ between males and females, especially with regard to blood accumulation of ND proteins and mechanisms of antioxidant responses to regular exercise. [ABSTRACT FROM AUTHOR]

Introduction: Urinary tract infection (UTI) is a major global health concern. While acute UTIs can usually be effectively treated, recurrent UTIs (rUTIs) impact patients for years, causing significant morbidity and can become refractory to front-line antibiotics. Areas covered: This review discusses the risk factors associated with rUTI, current rUTI treatment paradigms, prophylactic strategies, and challenges in rUTI diagnostics. We specifically discuss common risk factors for rUTI, including biological sex, age, menopause status, and diabetes mellitus. We also review recently available evidence for commonly used treatments, from oral antibiotic therapy to intravesical antimicrobials, electrofulguration of chronic cystitis, and the last-resort treatment, cystectomy. We discuss the most current literature evaluating prophylactic strategies for rUTI including long-term antibiotic prophylaxis, estrogen hormone therapy, and dietary supplements. Finally, we address the important role of UTI diagnostics in effective rUTI management and review the strengths and limitations of both current and emerging UTI diagnostic platforms as well as their ability to operate at point-of-care. Expert opinion: We discuss the current challenges faced by clinicians in managing rUTI in women and the steps that should be taken so that clinicians, scientists, and patients can work together to better understand the disease and develop better strategies for its management. [ABSTRACT FROM AUTHOR]

Simple Summary: The impacts of biological sex on cancer treatment outcomes are understudied, but differences in immune-related adverse events and oncologic outcomes have been associated with biological sex for patients with melanoma receiving checkpoint blockade therapy. In a recent trial, we also identified a difference in clinical outcomes between biological female and male patients with metastatic melanoma who received an experimental melanoma vaccine. Here, we examine whether treatment-related adverse events with the vaccine differ by biological sex. Background/Objective: Biological females experience more autoimmune disease than males and more treatment-related adverse events (TRAEs) after immune checkpoint blockade therapy. However, little is known about sex-related differences in TRAEs after cancer vaccines. Methods: The Mel44 clinical trial (NCT00118274) enrolled 167 eligible patients with high-risk melanoma to treatment with either of two melanoma multipeptide vaccines. We hypothesized that females would experience higher rates and grades of TRAEs. TRAE rates and grades were compared between sexes, with adjustment for multiple comparisons, and with mixed-effects models. Results: Multiple sex-related differences in TRAE rate and grade were observed in unadjusted comparisons, but only hyperglycemia and hypopigmentation were significantly higher-grade by sex after correcting for multiple comparisons: they were increased in males. In mixed-effect models, vaccination strategy, but not patient sex, was independently associated with TRAE rates and grades. Conclusions: These data do not support our hypothesis that TRAEs would be increased in females. Vaccine safety was supported for both males and females. [ABSTRACT FROM AUTHOR]

LEAP2, a liver-derived antagonist for the ghrelin receptor, GHSR1a, counteracts the effects of ghrelin on appetite and energy balance. Less is known about its impact on blood glucose-regulating hormones from pancreatic islets. Here, we investigate whether acyl-ghrelin (AG) and LEAP2 regulate islet hormone release in a cell-type- and sex-specific manner. Hormone content from secretion experiments with isolated islets from male and female mice was measured by radioimmunoassay and mRNA expression by qPCR. LEAP2 enhanced insulin secretion in islets from males (P < 0.01) but not females (P > 0.2), whilst AG-stimulated somatostatin release was significantly reversed by LEAP2 in males (P < 0.001) but not females (P > 0.2). Glucagon release was not significantly affected by AG and LEAP2. Ghsr1a, Ghrelin, Leap2, Mrap2, Mboat4, and Sstr3 islet mRNA expression did not differ between sexes, whereas the SSTR3 antagonist MK4256 enhanced glucose-induced insulin secretion in islets from males only. In control male islets maintained without 17-beta oestradiol (E2), AG exerted an insulinostatic effect (P < 0.05), with a trend towards reversal by LEAP2 (P = 0.06). Both were abolished by 72 h E2 pre-treatment (10 nmol/L, P > 0.2). AG-stimulated somatostatin release was inhibited by LEAP2 from control (P < 0.001) but not E2-treated islets (P > 0.2). LEAP2 and AG did not modulate insulin secretion from MIN6 beta cells and Mrap2 was downregulated (P < 0.05) and Ghsr1a upregulated (P < 0.0001) in islets from Sst-/- mice. Our findings show that AG and LEAP2 regulate insulin and somatostatin release in an opposing and sex-dependent manner, which in males can be modulated by E2. We suggest that regulation of SST release is a key starting point for understanding the role of GHSR1a in islet function and glucose metabolism. [ABSTRACT FROM AUTHOR]

Negative life events (NLEs) are associated with psychopathology in older adolescents and adults, particularly for women. However, less is known about the association between positive life events (PLEs) and psychopathology. This study examined associations between NLEs, PLEs, and their interaction, and sex differences in associations between PLEs and NLEs on internalizing and externalizing psychopathology. Youth completed interviews about NLEs and PLEs. Parents and youth reported on youth internalizing and externalizing symptoms. NLEs were positively associated with youth-reported depression and anxiety and parent-reported youth depression. Female youth had stronger positive associations between NLEs and youth-reported anxiety than male youth. Interactions between PLEs and NLEs were non-significant. Findings for NLEs and psychopathology are extended to earlier in development. [ABSTRACT FROM AUTHOR]

Objective: Comorbidity of epilepsy and autism in tuberous sclerosis complex 2 (TSC2) is very frequent, but the link between these conditions is still poorly understood. To study neurological problems related to autism, the scientific community has been using an animal model of TSC2, Tsc2+/− mice. However, it is still unknown whether this model has the propensity to exhibit increased seizure susceptibility. Further, the importance of sex and/or the circadian cycle in this biological process has never been addressed. This research aimed to determine whether male and female Tsc2+/− mice have altered seizure susceptibility at light and dark phases. Methods: We assessed seizure susceptibility and progression in a Tsc2+/− mouse model using the chemical convulsant kainic acid (KA), a potent agonist of the AMPA/kainate class of glutamate receptors. Both male and female animals at adult age were evaluated during non‐active and active periods. Seizure severity was determined by integrating individual scores per mouse according to a modified Racine scale. Locomotor behavior was monitored during control and after KA administration. Results: We found increased seizure susceptibility in Tsc2+/− mice with a significant influence of sex and circadian cycle on seizure onset, progression, and behavioral outcomes. While, compared to controls, Tsc2+/− males overall exhibited higher susceptibility independently of circadian cycle, Tsc2+/− females were more susceptible during the dark and post‐ovulatory phase. Interestingly, sexual dimorphisms related to KA susceptibility were always reported during light phase independently of the genetic background, with females being the most vulnerable. Significance: The enhanced susceptibility in the Tsc2 mouse model suggests that other neurological alterations, beside brain lesions, may be involved in seizure occurrence for TSC. Importantly, our work highlighted the importance of considering biological sex and circadian cycle for further studies of TSC‐related epilepsy research. Plain Language Summary: Tuberous sclerosis complex (TSC) is a rare genetic disorder. It causes brain lesions and is linked to epilepsy, intellectual disability, and autism. We wanted to investigate epilepsy in this model. We found that these mice have more induced seizures than control animals. Our results show that these mice can be used in future epilepsy research for this disorder. We also found that sex and time of day can influence the results. This must be considered in this type of research. [ABSTRACT FROM AUTHOR]

Fetal growth restriction (FGR) is a common complication of pregnancy, associated with major perinatal mortality and morbidity, and with an increased risk to develop cardiometabolic diseases later in life. There is currently no effective approach to prevent or treat FGR, despite numerous animal and human studies assessing substances likely to improve fetal growth. Phosphodiesterase (PDE) inhibitors appeared as promising drugs to improve FGR management. However, to date, studies have led to somewhat disappointing or controversial results. In this Opinion article, we would like to draw attention to the need to consider the biological sex and the relative reactivity of human umbilical vein and arteries when developing therapeutic interventions to improve human umbilical circulation using PDE inhibitors. Indeed, we suspect that fetal sex, vessel type and the presence of FGR may influence subcellular compartmentation, which could jeopardize beneficial effects of PDE inhibitors. [ABSTRACT FROM AUTHOR]

Electroencephalographic (EEG) microstates can provide a unique window into the temporal dynamics of large-scale brain networks across brief (millisecond) timescales. Here, we analysed fundamental temporal features of microstates extracted from the broadband EEG signal in a large (N = 139) cohort of children spanning early-to-middle childhood (4-12 years of age). Linear regression models were used to examine if participants age and biological sex could predict the temporal parameters GEV, duration, coverage, and occurrence, for five microstate classes (A-E) across both eyes-closed and eyes-open resting-state recordings. We further explored associations between these microstate parameters and posterior alpha power after removal of the 1/f-like aperiodic signal. The microstates obtained from our neurodevelopmental EEG recordings broadly replicated the four canonical microstate classes (A to D) frequently reported in adults, with the addition of the more recently established microstate class E. Biological sex served as a significant predictor in the regression models for four of the five microstate classes (A, C, D, and E). In addition, duration and occurrence for microstate E were both found to be positively associated with age for the eyes-open recordings, while the temporal parameters of microstates C and E both exhibited associations with alpha band spectral power. Together, these findings highlight the influence of age and sex on large-scale functional brain networks during early-to-middle childhood, extending understanding of neural dynamics across this important period for brain development.

Males are diagnosed with autism much more frequently than females, and most research study samples reflect this male predominance. The result is that autistic females are understudied. There is a critical need to increase our understanding of autistic females, both biologically and clinically. The only way to do this is to recruit sex-balanced cohorts in studies so that similarities and differences between males and females can be evaluated in all autism research studies. The purpose of this commentary is to (1) provide historical context about how females came to be under-represented in all research, not just in the field of autism and (2) learn from other areas of health and medicine about the potentially dire consequences of not studying both sexes, and (3) draw attention to the need to recruit sex-balanced cohorts in autism research, particularly in neuroimaging studies.

Abstract Background Social behaviour plays a key role in mental health and wellbeing, and developing greater understanding of mechanisms underlying social interaction—particularly social motivation—holds substantial transdiagnostic impact. Common rodent behavioural assays used to assess social behaviour are limited in their assessment of social motivation, whereas the social operant conditioning model can provide unique and valuable insights into social motivation. Further characterisation of common experimental parameters that may influence social motivation within the social operant model, as well as complementary methodological and analytical approaches, are warranted. Methods This study investigated the effects of biological sex, housing condition, and time-of-day, on social motivation using the social operant model. This involved training rats to lever press (FR1) for 60-s access to a social reward (same-sex conspecific stimulus). Subjects were male and female Wistar rats, housed under individual or paired conditions, and sessions were conducted either in the mid-late light phase (ZT6-10) or early-mid dark phase (ZT13-17). A behavioural economics approach was implemented to measure social demand and the influence of stimulus partner sex (same- vs. opposite-sex stimulus) on social operant responding. Additionally, video tracking analyses were conducted to assess the degree of convergence between social appetitive and consummatory behaviours. Results Biological sex, housing conditions, the interaction between sex and housing, and stimulus partner sex potently influenced social motivation, whereas time-of-day did not. Behavioural economics demonstrated that sex, housing, and their interaction influence both the hedonic set-point and elasticity of social demand. Video analysis of social interaction during social operant sessions revealed that social appetitive and consummatory behaviours are not necessarily convergent, and indicate potential social satiety. Lastly, oestrus phase of female experimental and stimulus rats did not impact social motivation within the model. Conclusions Social isolation-dependent sex differences exist in social motivation for rats, as assessed by social operant conditioning. The social operant model represents an optimal preclinical assay that comprehensively evaluates social motivation and offers a platform for future investigations of neurobiological mechanisms underlying sex differences in social motivation. These findings highlight the importance of continued consideration and inclusion of sex as a biological variable in future social operant conditioning studies. Plain English summary Humans are social creatures—our everyday interactions with others and the support this provides play a key role in our wellbeing. For those experiencing mental health conditions, people’s motivation to engage with others can wane, which can lead them to withdraw from those who support them. Therefore, to develop better treatment strategies for these conditions, we need to gain a deeper understanding of social motivation. Studying social behaviour in animals can facilitate this investigation of social motivation as it allows for a causal understanding of underlying neurobiology that is not possible in human experiments. An optimal way to study social motivation in animals is using the social operant conditioning model, where rats learn to press a lever that opens a door and allows them to interact with another rat for a short time. This study characterised the social operant model by testing whether sex, housing conditions, time-of-day, and the sex of the stimulus partner influence rats’ motivation to seek interaction with another rat. We found that female rats were more socially motivated than males, and that rats living alone were more motivated than those living with another rat; interestingly, this effect of housing affected females more than males. Regardless of sex, rats were more motivated to interact with a rat of the opposite sex. These findings provide insights into sex differences in social motivation in rats and new insights into the social operant model which will help guide future research into social motivation and other mental health conditions.

Fungal infections often disproportionately affect males over females. Since the NIH mandated in 2016 that researchers test their hypotheses in both biological sexes, numerous other fungal infections/colonizations have been found to exhibit sex-specific patterns. These patterns have been observed in various species, including mice, drosophila, cats, and bats, suggesting significant implications for understanding these diseases and developing treatments. Despite the recognition of this sex bias, primary research explaining its underlying causes or mechanisms remains limited. Current evidence suggests that potential causes might be linked to sex hormones, genetic expression, and evolutionary behaviors. This review consolidates recent data on sex bias in fungal infections or colonizations among different species and proposes future research directions to address existing gaps. Thus, this review advances the comprehension of the intricate relationships between biological sex, fungal infections, and broader health implications. [ABSTRACT FROM AUTHOR]

Cancer cachexia (CC) is a multifactorial and complex syndrome experienced by up to 80% of patients with cancer and implicated in ∼40% of cancer-related deaths. Given its significant impact on patients' quality of life and prognosis, there has been a growing emphasis on elucidating the underlying mechanisms of CC using preclinical models. However, the mechanisms of cachexia appear to differ across several variables including tumor type and model and biologic variables such as sex. These differences may be exacerbated by variance in experimental approaches and data reporting. This review examines literature spanning from 2011 to March 2024, focusing on common preclinical models of CC, including Lewis Lung Carcinoma, pancreatic KPC, and colorectal colon-26 and Apcmin/+ models. Our analysis reveals considerable heterogeneity in phenotypic outcomes, and investigated mechanisms within each model, with particular attention to sex differences that may be exacerbated through methodological differences. Although searching for unified mechanisms is critical, we posit that effective treatment approaches are likely to leverage the heterogeneity presented by the tumor and pertinent biological variables to direct specific interventions. In exploring this heterogeneity, it becomes critical to consider methodological and data reporting approaches to best inform further research. [ABSTRACT FROM AUTHOR]

Simple Summary: Over the course of the past 3 million years, changes in human habitats, nutrition and behaviour have led to continuous processes of shape modification and size reduction in our jaws and teeth. These have resulted in the specific masticatory system observed today and the widespread need for orthodontic treatment. The aim of this study was to identify correlations between tooth sizes, jaw dimensions, biological sex and stature in a central European sample. We observed differences between women and men with regard to their tooth and jaw dimensions. In general, men's teeth, especially the canines, are larger. There are also differences in tooth sizes and jaw dimensions in relation to stature, with the canines again standing out. Our results help us to better understand the evolutionary trends affecting our teeth. They also indicate that, while the basic sexual dimorphisms of our primate ancestors have been retained, modern dietary habits will further intensify the reduction in the masticatory apparatus. Furthermore, the results provide sex-specific metric data of forensic significance, as well as clues as to why more and more people require orthodontic treatment, while suggesting possible causes for diachronic differences in tooth and jaw dimensions between populations. Dental anthropology provides a deep insight into biological, ecological and cultural aspects associated with human individuality, behaviour and living conditions and the environment. Our study uses a correlation analysis to test the metric relationships between tooth sizes and jaw dimensions and juxtaposes them with biological sex and stature. A sample of n = 100 dental casts was used to record metric dental data including the mesio-distal and bucco-lingual tooth crown diameters and nine upper and lower jaw dimensions. All crown diameters were highly correlated with both stature and biological sex, with the canines exhibiting the highest correlation. The majority of jaw dimensions exhibited similar correlations. Our results suggest that the differences between the sexes in most crown diameters and some jaw dimensions may be related to the stature of the individuals measured. Two groups of closely correlating features emerged among the jaw dimensions, differing in their degree of correlation with crown diameters and with sex. The results and insights obtained are highly relevant for evolutionary biology, dentistry, craniofacial research, bioarchaeology and forensic odontology. [ABSTRACT FROM AUTHOR]

Copyright of Health Psychology is the property of American Psychological Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This study examined the association between prenatal cannabis exposure and autism spectrum disorder (ASD) diagnoses and traits. A total sample of 11,570 children (ages 1–18; 53% male; 25% Hispanic; 60% White) from 34 cohorts of the National Institutes of Health‐funded environmental influences on child health outcomes consortium were included in analyses. Results from generalized linear mixed models replicated previous studies showing that associations between prenatal cannabis exposure and ASD traits in children are not significant when controlling for relevant covariates, particularly tobacco exposure. Child biological sex did not moderate the association between prenatal cannabis exposure and ASD. In a large sample and measuring ASD traits continuously, there was no evidence that prenatal cannabis exposure increases the risk for ASD. This work helps to clarify previous mixed findings by addressing concerns about statistical power and ASD measurement. Lay Summary: This study examined the relationship between prenatal cannabis exposure and autism traits. We found that there was no association between maternal cannabis use during pregnancy and child autism traits once potential confounds were controlled. Although there was no evidence that prenatal cannabis exposure increases the risk for autism traits, prenatal cannabis exposure may still be associated with other facets of child development and behavior that were outside of the scope of this study. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate whether endothelin‐A receptor (ETAR) inhibition in non‐Hispanic Black (NHB) and White (NHW) young adults depends on biological sex. We recruited females during low hormone (n = 22) and high hormone (n = 22) phases, and males (n = 22). Participants self‐identified as NHB (n = 33) or NHW (n = 33). Participants were instrumented with two microdialysis fibers: (1) lactated Ringer's (control) and (2) 500 nM BQ‐123 (ETAR antagonist). Local heating was used to elicit cutaneous vasodilation, and an infusion of 20 mM L‐NAME to quantify NO‐dependent vasodilation. At control sites, NO‐dependent vasodilation was lowest in NHB males (46 ± 13 %NO) and NHB females during low hormone phases (47 ± 12 %NO) compared to all NHW groups. Inhibition of ETAR increased NO‐dependent vasodilation in NHB males (66 ± 13 %NO), in both groups of females during low hormone phases (NHW, control: 64 ± 12 %NO, BQ‐123: 85 ± 11 %NO; NHB, BQ‐123: 68 ± 13 %NO), and in NHB females during high hormone phases (control: 61 ± 11 %NO, BQ‐123: 83 ± 9 %NO). There was no effect for ETAR inhibition in NHW males or females during high hormone phases. These data suggest the effect of ETAR inhibition on NO‐dependent vasodilation is influenced by biological sex and racial identity. [ABSTRACT FROM AUTHOR]

Background: Social behaviour plays a key role in mental health and wellbeing, and developing greater understanding of mechanisms underlying social interaction—particularly social motivation—holds substantial transdiagnostic impact. Common rodent behavioural assays used to assess social behaviour are limited in their assessment of social motivation, whereas the social operant conditioning model can provide unique and valuable insights into social motivation. Further characterisation of common experimental parameters that may influence social motivation within the social operant model, as well as complementary methodological and analytical approaches, are warranted. Methods: This study investigated the effects of biological sex, housing condition, and time-of-day, on social motivation using the social operant model. This involved training rats to lever press (FR1) for 60-s access to a social reward (same-sex conspecific stimulus). Subjects were male and female Wistar rats, housed under individual or paired conditions, and sessions were conducted either in the mid-late light phase (ZT6-10) or early-mid dark phase (ZT13-17). A behavioural economics approach was implemented to measure social demand and the influence of stimulus partner sex (same- vs. opposite-sex stimulus) on social operant responding. Additionally, video tracking analyses were conducted to assess the degree of convergence between social appetitive and consummatory behaviours. Results: Biological sex, housing conditions, the interaction between sex and housing, and stimulus partner sex potently influenced social motivation, whereas time-of-day did not. Behavioural economics demonstrated that sex, housing, and their interaction influence both the hedonic set-point and elasticity of social demand. Video analysis of social interaction during social operant sessions revealed that social appetitive and consummatory behaviours are not necessarily convergent, and indicate potential social satiety. Lastly, oestrus phase of female experimental and stimulus rats did not impact social motivation within the model. Conclusions: Social isolation-dependent sex differences exist in social motivation for rats, as assessed by social operant conditioning. The social operant model represents an optimal preclinical assay that comprehensively evaluates social motivation and offers a platform for future investigations of neurobiological mechanisms underlying sex differences in social motivation. These findings highlight the importance of continued consideration and inclusion of sex as a biological variable in future social operant conditioning studies. Plain English summary: Humans are social creatures—our everyday interactions with others and the support this provides play a key role in our wellbeing. For those experiencing mental health conditions, people's motivation to engage with others can wane, which can lead them to withdraw from those who support them. Therefore, to develop better treatment strategies for these conditions, we need to gain a deeper understanding of social motivation. Studying social behaviour in animals can facilitate this investigation of social motivation as it allows for a causal understanding of underlying neurobiology that is not possible in human experiments. An optimal way to study social motivation in animals is using the social operant conditioning model, where rats learn to press a lever that opens a door and allows them to interact with another rat for a short time. This study characterised the social operant model by testing whether sex, housing conditions, time-of-day, and the sex of the stimulus partner influence rats' motivation to seek interaction with another rat. We found that female rats were more socially motivated than males, and that rats living alone were more motivated than those living with another rat; interestingly, this effect of housing affected females more than males. Regardless of sex, rats were more motivated to interact with a rat of the opposite sex. These findings provide insights into sex differences in social motivation in rats and new insights into the social operant model which will help guide future research into social motivation and other mental health conditions. Highlights: Female Wistar rats exhibited greater social motivation than male rats in the social operant conditioning model. Isolated housing produced higher social motivation than paired housing, but this isolation-induced increase was either more marked for, or only present in, female rats. Both female and male rats demonstrate higher motivation for opposite-sex than same-sex stimulus conspecifics. Time-of-day and oestrus phase (of female experimental and stimulus rats) did not appear to impact social motivatio. Both between- and within-session behavioural economics in conjunction with video tracking analyses can be applied to better assess social motivation and interaction during social operant conditioning. [ABSTRACT FROM AUTHOR]

Estimating biological sex is a fundamental step in assessing the biological profile of human remains, whether recovered from archaeo-anthropological or forensic contexts. As the methods based on the os coxae are not systematically applicable, alternative means of sexual diagnosis are needed. This morphometric study examines the sexual dimorphism of the cranial base (i.e., occipital, temporal bones and bony labyrinth) using a corpus of 611 skulls and 121 bony labyrinths from identified individuals – both immature and adult – from Western Europe. The study shows how the expression of this sexual dimorphism becomes more marked on the temporal bone as from the pubertal growth peak. Thirteen predictive models, with a classification accuracy ranging from 77 to 87% with a 0.70 decision threshold, were developed based on the adult cranial base. The models were also applied, successfully, to 3D cranial surfaces. Our study demonstrates that an age-independent sex estimation method cannot be designed on the bony labyrinth. Taking into account the specific features of immature and adult sexual dimorphism, predictive models were built up that yielded, respectively, up to 76-83% and 73-86% accuracy. This research thus offers a new method of sexual diagnosis which is better suited to fragmentary adult remains, and thereby contributes to the discussion about the need to set up a standardized analytical framework for future developments in sexing methods.

In mammals, trait variation is often reported to be greater among males than females. However, to date, mainly only morphological traits have been studied. Energy expenditure represents the metabolic costs of multiple physical, physiological, and behavioral traits. Energy expenditure could exhibit particularly high greater male variation through a cumulative effect if those traits mostly exhibit greater male variation, or a lack of greater male variation if many of them do not. Sex differences in energy expenditure variation have been little explored. We analyzed a large database on energy expenditure in adult humans (1494 males and 3108 females) to investigate whether humans have evolved sex differences in the degree of interindividual variation in energy expenditure. We found that, even when statistically comparing males and females of the same age, height, and body composition, there is much more variation in total, activity, and basal energy expenditure among males. However, with aging, variation in total energy expenditure decreases, and because this happens more rapidly in males, the magnitude of greater male variation, though still large, is attenuated in older age groups. Considerably greater male variation in both total and activity energy expenditure could be explained by greater male variation in levels of daily activity. The considerably greater male variation in basal energy expenditure is remarkable and may be explained, at least in part, by greater male variation in the size of energy-demanding organs. If energy expenditure is a trait that is of indirect interest to females when choosing a sexual partner, this would suggest that energy expenditure is under sexual selection. However, we present a novel energetics model demonstrating that it is also possible that females have been under stabilizing selection pressure for an intermediate basal energy expenditure to maximize energy available for reproduction.

It is unclear what effect biological sex has on outcomes of acute lung injury (ALI). Clinical studies are confounded by their observational design. We addressed this knowledge gap with a preclinical systematic review of ALI animal studies. We searched MEDLINE and Embase for studies of intratracheal/intranasal/aerosolized lipopolysaccharide administration (the most common ALI model) that reported sex-stratified data. Screening and data extraction were conducted in duplicate. Our primary outcome was histological tissue injury and secondary outcomes included alveolar-capillary barrier alterations and inflammatory markers. We used a random-effects inverse variance meta-analysis, expressing data as standardized mean difference (SMD) with 95% confidence intervals (CIs). Risk of bias was assessed using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) tool. We identified six studies involving 132 animals across 11 independent experiments. A total of 41 outcomes were extracted, with the direction of effect suggesting greater severity in males than females in 26/41 outcomes (63%). One study reported on lung histology and found that male mice exhibited greater injury than females (SMD: 1.61, 95% CI: 0.53–2.69). Meta-analysis demonstrated significantly elevated albumin levels (SMD: 2.17, 95% CI: 0.63–3.70) and total cell counts (SMD: 0.80, 95% CI: 0.27–1.33) in bronchoalveolar lavage fluid from male mice compared with female mice. Most studies had an “unclear risk of bias.” Our findings suggest sex-related differences in ALI severity. However, these conclusions are drawn from a small number of animals and studies. Further research is required to address the fundamental issue of biological sex differences in LPS-induced ALI. [ABSTRACT FROM AUTHOR]

Background: Females are disproportionately affected by strokes when compared to males. This may be attributed to non-traditional stroke symptoms in females and stroke care sex variance. This study explored sex and ethnicity discrepancies in the FAST-ED and stroke outcomes. Methods: An internal hospital registry created in 2017 evaluated EMS FAST-ED compliance and monitored patient outcomes. We assessed two cohorts, the 2017 cohort collected one year after FAST-ED implementation, and the 2019 cohort collected two years after FAST-ED implementation. Inclusion criteria included patients aged ≥18 years arriving via EMS as a stroke alert; walk-ins were excluded. EMS FAST-ED compliance, FAST-ED score, final diagnoses, door to needle time (DTN), door to puncture (DTP) time, and stroke treatment volumes were evaluated for sex differences. Results: 1,156 cases were analyzed, 638 (55%) were female. EMS FAST-ED compliance decreased by 17%, but did not differ by sex or ethnicity. EMS FAST-ED score was similar for females and males. Despite the similarity in FAST-ED score, females scored higher on the initial NIHSS (F (1) = 6.25, p <.05) and discharge NIHSS (F (1) = 8.588, p <.01). Those diagnosed with a stroke were 1.4 times more likely to be female (χ²wald = 6.21, p <.01, 95% CI [1.07–1.80]). Treatment rates did not vary between sex or ethnicity and overall DTN decreased by 10 minutes (2017 cohort M = 36 minutes, SE = 1.96; 2019 cohort M = 26 minutes, SE = 1.69). Conclusions: The FAST-ED demonstrated equitable implementation and scoring among a diverse population, regardless of sex or ethnicity. Additionally, patients were equally likely to receive treatment, while benefiting from a decrease in DTN times. [ABSTRACT FROM AUTHOR]

Background There is evidence of an association of severe coroanavirus disease (COVID-19) outcomes with increased body mass index (BMI) and male sex. However, few studies have examined the interaction between sex and BMI on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral dynamics. Methods Participants conducted RT-PCR testing every 24–48 hours over a 15-day period. Sex and BMI were self-reported, and Ct values from E-gene were used to quantify viral load. Three distinct outcomes were examined using mixed-effects generalized linear models, linear models, and logistic models, respectively: all Ct values (model 1), nadir Ct value (model 2), and strongly detectable infection (at least 1 Ct value ≤28 during their infection) (model 3). An interaction term between BMI and sex was included, and inverse logit transformations were applied to quantify the differences by BMI and sex using marginal predictions. Results In total, 7988 participants enrolled in this study and 439 participants (model 1) and 309 (models 2 and 3) were eligible for these analyses. Among males, increasing BMI was associated with lower Ct values in a dose-response fashion. For participants with BMIs greater than 29 kg/m2, males had significantly lower Ct values and nadir Ct values than females. In total, 67.8% of males and 55.3% of females recorded a strongly detectable infection; increasing proportions of men had Ct values <28 with BMIs of 35 and 40 kg/m2. Conclusions We observed sex-based dimorphism in relation to BMI and COVID-19 viral load. Further investigation is needed to determine the cause, clinical impact, and transmission implications of this sex-differential effect of BMI on viral load. [ABSTRACT FROM AUTHOR]

IntroductionAs personalized medicine advances, the need to explore periodontal health across different sexes and gender identities becomes crucial. This narrative review addresses the gap in understanding how biological sex and gender-affirming hormone therapy (GAHT) influence periodontitis risk.ResultsResearch has uncovered significant sex-based immunological disparities driven by X and Y chromosome gene expression and sex-hormones, which may influence susceptibility to periodontitis. Additionally, preliminary findings suggest that GAHT, particularly testosterone therapy in transgender men, could exacerbate pro-inflammatory cytokine production and alter immune cell responses, which may exacerbate inflammatory pathways crucial in the progression of periodontitis. Conversely, the effects of estrogen therapy in transgender women, although less extensively studied, suggest modifications in B cell functionality. These observations highlight the complex role of GAHT in modulating immune responses that are central to the development and exacerbation of periodontal disease.DiscussionThe review highlights a complex interaction between sex hormones, gene expression patterns, immune responses, and periodontitis risk. While cisgender males show increased susceptibility to periodontitis that could be linked to specific immune pathways, GAHT appears to modify these pathways in transgender individuals, potentially altering their risk and disease progression patterns.ConclusionThere is a critical need for more focused research on the direct impacts of GAHT on periodontal health. Understanding the nuances of immune modulation by GAHT will aid in crafting personalized periodontal care for transgender individuals, aligning with the broader goals of inclusive and effective healthcare.

Prevalence estimates of sibling bullying indicate it occurs more frequently and with more negative consequences than peer bullying, yet many countries do not track or investigate the phenomenon. University students from Argentina, Estonia, and the United States were surveyed to investigate their retrospective experiences involving sibling bullying, how often it occurred, the roles held, and the forms communicated. In the aggregated data, roughly 50 % of the sampled emerging adults (N = 3477) reported experience with sibling bullying, with the dual role of bully-victim being the most frequently reported role held by males and females, with the second role being bully for males and victim for females. Verbal forms of bullying were most frequently reported by males and females, with physical, relational, and technological forms occurring less frequently, indicating the importance of studying the messages conveyed during bullying incidents. Variations between biological sex, bullying role and form were detected that indicate siblings experience bullying in ways that are unique from peer bullying. Country comparisons revealed bullying frequencies varied among males and females, suggesting sibling bullying experiences are likely to be culturally influenced. More research is warranted to examine the negative impact bullying has on sibling psycho-social development and the potential transfer to non-familial relationships and contexts. Discussion of these findings and the implications for academics and practitioners alike is provided.

Background Intracranial aneurysms (IAs) are more common in women than in men; however, there is still limited knowledge on sex‐dependent differences regarding aneurysm location, multiplicity, rupture risk, risk factors, and histopathology. Methods This cross‐sectional, consecutive cohort study examined whether IAs differ in multiplicity, location, geometry, rupture risk, risk factors, and histology between sexes. Results We included 982 patients (714 women, 268 men) totaling 1484 IAs (1056 unruptured, 397 ruptured). A total of 363 patients (36.97%) had multiple IAs, the proportion of which was significantly higher in women. In women, the internal carotid artery (40.79%) was the most frequent location for IAs, whereas in men most were found along the anterior carotid artery territory (32.86%). Men were significantly more often diagnosed with ruptured aneurysms. Aneurysm geometry did not differ between sexes; however, ruptured aneurysms in men presented with a significantly larger neck diameter than unruptured ones. Regarding risk factors for aneurysm rupture, blood pressure control was more effective in women, whereas the effect of smoking status did not show clear sex‐dependent differences. Histologically, wall‐type classification analysis showed significantly more severe aneurysm wall types in men. Conclusion IA prevalence in women is significantly higher than in men. Women more often present with multiple IAs, whereas men were more often diagnosed with ruptured IAs. Sex‐specific differences in IA location were identified, whereas geometry of IAs did not differ between sexes. IAs in men showed a more severe histological wall type. Further research is needed to unravel the molecular mechanisms underlying these important sex‐dependent manifestations in IAs.

Abstract The Y-box binding protein-1 (YBX1) gene codes for a multifunctional oncoprotein that is increasingly being linked to the regulations of many aspects of cancer cell biology. Disparities in treatment outcomes between male and female cancer patients are increasingly reported. This study aimed to examine the relationship between YBX1 expression and overall survival in male and female patients with solid tumours. Overall survival and YBX1 expression data for cohorts of male and female cancer patients obtained from freely available databases were analysed with a cox proportional hazard model with covariates of biological sex and YBX1 expression. Kaplan–Meier curves and Violin plots were constructed for segregated male and female cohorts. High YBX1 expression was significantly associated with poor survival in 2 female-only and 4 mixed-sex cancer sites. In female lung cancer patients, better survival and lower YBX1 expression were identified. The clinical importance of YBX1 expression in cancer ought to be evaluated in a sex-specific manner, especially in lung cancer.

Abstract Background Sex differences exist in the risk of developing type 1 and type 2 diabetes, and in the risk of developing diabetes-associated complications. Sex differences in glucose homeostasis, islet and β cell biology, and peripheral insulin sensitivity have also been reported. Yet, we lack detailed information on the mechanisms underlying these differences, preventing the development of sex-informed therapeutic strategies for persons living with diabetes. To chart a path toward greater inclusion of biological sex as a variable in diabetes research, we first need a detailed assessment of common practices in the field. Methods We developed a scoring system to evaluate the inclusion of biological sex in manuscripts published in Diabetes, a journal published by the American Diabetes Association. We chose Diabetes as this journal focuses solely on diabetes and diabetes-related research, and includes manuscripts that use both clinical and biomedical approaches. We scored papers published across 3 years within a 20-year period (1999, 2009, 2019), a timeframe that spans the introduction of funding agency and journal policies designed to improve the consideration of biological sex as a variable. Results Our analysis showed fewer than 15% of papers used sex-based analysis in even one figure across all study years, a trend that was reproduced across journal-defined categories of diabetes research (e.g., islet studies, signal transduction). Single-sex studies accounted for approximately 40% of all manuscripts, of which > 87% used male subjects only. While we observed a modest increase in the overall inclusion of sex as a biological variable during our study period, our data highlight significant opportunities for improvement in diabetes research practices. We also present data supporting a positive role for journal policies in promoting better consideration of biological sex in diabetes research. Conclusions Our analysis provides significant insight into common practices in diabetes research related to the consideration of biological sex as a variable. Based on our analysis we recommend ways that diabetes researchers can improve inclusion of biological sex as a variable. In the long term, improved practices will reveal sex-specific mechanisms underlying diabetes risk and complications, generating knowledge to enable the development of sex-informed prevention and treatment strategies.

Fetal growth restriction (FGR) is a common complication of pregnancy, associated with major perinatal mortality and morbidity, and with an increased risk to develop cardiometabolic diseases later in life. There is currently no effective approach to prevent or treat FGR, despite numerous animal and human studies assessing substances likely to improve fetal growth. Phosphodiesterase (PDE) inhibitors appeared as promising drugs to improve FGR management. However, to date, studies have led to somewhat disappointing or controversial results. In this Opinion article, we would like to draw attention to the need to consider the biological sex and the relative reactivity of human umbilical vein and arteries when developing therapeutic interventions to improve human umbilical circulation using PDE inhibitors. Indeed, we suspect that fetal sex, vessel type and the presence of FGR may influence subcellular compartmentation, which could jeopardize beneficial effects of PDE inhibitors.

Abstract Background Transcranial direct current stimulation (tDCS) can influence brain network activity and associated cognitive and behavioural functions. In addition to the extensive variety in stimulation parameters, numerous biological factors drive these effects, however these are yet poorly understood. Here, we investigate one of the major biological factors by focusing on sex-dependent effects of tDCS on a challenging cognitive control task (adaptive paced auditory serial addition task [PASAT]) in healthy humans. Methods This sex-specific re-analysis was performed on data of 163 subjects who underwent a 2-week cognitive control training (6 sessions in total). Subjects received either verum (anodal/cathodal) or sham tDCS. Electrodes were placed over the left or right dorsolateral prefrontal cortex and the respective contralateral deltoid muscle. Cognitive control was measured as performance in the PASAT and was analysed in respect to stimulation conditions (sham, anodal, cathodal) and sex. Results Regardless of stimulation condition, performance gains between the sexes were higher in females compared to males (p = 0.0038). Female’s performance during anodal tDCS exceeded male’s (p = 0.0070), yet no effects were found for cathodal or sham tDCS. Moreover, in females we found a superior effect for anodal tDCS over sham stimulation (fanodal: p = 0.0354; fcathodal: p = 0.6181), but no such effect in males (manodal: p = 0.6882; mcathodal: p = 0.4822). Conclusions This study highlights the relevance of biological sex for the effects of tDCS on cognitive training. Thus, an increased attention to biological sex is advisable in future brain stimulation research to highlight and in consequence better understand potentially underlying sex-specific mechanisms. Considering biological sex will further advance customisation and individualisation of tDCS interventions. Trial registration ClinicalTrials.gov, NCT04108663.

The article examines the different interpretations of masculinity and femininity within the contexts of sociology, cultural studies, and psychology. In sociology, gender roles are considered to be socially constructed and variable, with feminist studies emphasizing the social construction of femininity in the context of gender inequality. In cultural studies, Hofstede views masculinity and femininity as cultural dimensions that influence societal attitudes and behavior. Overall, gender is interpreted as a complex of biological, social, and psychological aspects, which are expressed on a continuum and are often subject to social and cultural reconstruction. In psychology, these characteristics are associated with social and behavioral aspects, rather than with biological sex alone. Gender schema theory highlights that individuals can exhibit both masculine and feminine traits. Psychoanalysis introduces concepts of gender identity and the role of parents in the gender socialization of children.

The Y-box binding protein-1 (YBX1) gene codes for a multifunctional oncoprotein that is increasingly being linked to the regulations of many aspects of cancer cell biology. Disparities in treatment outcomes between male and female cancer patients are increasingly reported. This study aimed to examine the relationship between YBX1 expression and overall survival in male and female patients with solid tumours. Overall survival and YBX1 expression data for cohorts of male and female cancer patients obtained from freely available databases were analysed with a cox proportional hazard model with covariates of biological sex and YBX1 expression. Kaplan–Meier curves and Violin plots were constructed for segregated male and female cohorts. High YBX1 expression was significantly associated with poor survival in 2 female-only and 4 mixed-sex cancer sites. In female lung cancer patients, better survival and lower YBX1 expression were identified. The clinical importance of YBX1 expression in cancer ought to be evaluated in a sex-specific manner, especially in lung cancer. [ABSTRACT FROM AUTHOR]

The use of predators and predator odor as stressors is an important and ecologically relevant model for studying the impact of behavioral responses to threat. Here we summarize neural substrates and behavioral changes in rats resulting from predator exposure. We briefly define the impact predator exposure has on neural targets throughout development (neonatal, juvenile, and adulthood). These findings allow us to conceptualize the impact of predator exposure in the brain, which in turn may have broader implications for human disorders such as PTSD. Importantly, inclusion of sex as a biological variable yields distinct results that may indicate neural substrates impacted by predator exposure differ based on sex. [ABSTRACT FROM AUTHOR]

In this study, we consider the influence of biological sex-specific immune responses on the assessment of mRNA vaccines in pre-clinical murine studies. Recognising the established disparities in immune function attributed to genetic and hormonal differences between individuals of different biological sexes, we compared the mRNA expression and immune responses in mice of both biological sexes after intramuscular injection with mRNA incorporated within lipid nanoparticles. Regarding mRNA expression, no significant difference in protein (luciferase) expression at the injection site was observed between female and male mice following intramuscular administration; however, we found that female BALB/c mice exhibit significantly greater total IgG responses across the concentration range of mRNA lipid nanoparticles (LNPs) in comparison to their male counterparts. This study not only contributes to the scientific understanding of mRNA vaccine evaluation but also emphasizes the importance of considering biological sex in vaccine study designs during pre-clinical evaluation in murine studies. [ABSTRACT FROM AUTHOR]

Background: Sex differences exist in the risk of developing type 1 and type 2 diabetes, and in the risk of developing diabetes-associated complications. Sex differences in glucose homeostasis, islet and β cell biology, and peripheral insulin sensitivity have also been reported. Yet, we lack detailed information on the mechanisms underlying these differences, preventing the development of sex-informed therapeutic strategies for persons living with diabetes. To chart a path toward greater inclusion of biological sex as a variable in diabetes research, we first need a detailed assessment of common practices in the field. Methods: We developed a scoring system to evaluate the inclusion of biological sex in manuscripts published in Diabetes, a journal published by the American Diabetes Association. We chose Diabetes as this journal focuses solely on diabetes and diabetes-related research, and includes manuscripts that use both clinical and biomedical approaches. We scored papers published across 3 years within a 20-year period (1999, 2009, 2019), a timeframe that spans the introduction of funding agency and journal policies designed to improve the consideration of biological sex as a variable. Results: Our analysis showed fewer than 15% of papers used sex-based analysis in even one figure across all study years, a trend that was reproduced across journal-defined categories of diabetes research (e.g., islet studies, signal transduction). Single-sex studies accounted for approximately 40% of all manuscripts, of which > 87% used male subjects only. While we observed a modest increase in the overall inclusion of sex as a biological variable during our study period, our data highlight significant opportunities for improvement in diabetes research practices. We also present data supporting a positive role for journal policies in promoting better consideration of biological sex in diabetes research. Conclusions: Our analysis provides significant insight into common practices in diabetes research related to the consideration of biological sex as a variable. Based on our analysis we recommend ways that diabetes researchers can improve inclusion of biological sex as a variable. In the long term, improved practices will reveal sex-specific mechanisms underlying diabetes risk and complications, generating knowledge to enable the development of sex-informed prevention and treatment strategies. Plain language summary: Men and women have a different risk of developing type 1 and type 2 diabetes. Men and women also live with different complications of diabetes and show different treatment benefits. One reason for these differences is that biological sex affects diabetes risk, complications, and treatment efficacy. Unfortunately, a lot of diabetes research does not consider whether biological sex might affect the study results. As a result, we do not have enough information to match an individual's sex with the best diabetes prevention and treatment strategies. We are tackling this problem by learning how diabetes researchers consider biological sex in their studies. We read and scored over 800 diabetes research papers to see if, and how well, they considered biological sex in their study. Based on our results, we recommend several easy ways that diabetes researchers can do a better job of considering biological sex in their work. As more researchers consider biological sex, they will learn more about how an individual's sex affects diabetes risk, complications, and treatment effects. This information will benefit the diabetes community as a whole because it represents the first step toward matching an individual's sex with the best prevention and treatment strategies. Highlights: We found a modest improvement in the consideration of biological sex as a variable in diabetes research over 20 years. In single-sex animal studies males were used 87% of the time. Main barrier to inclusion of biological sex in clinical studies was failure to include biological sex as a variable in data analysis. Main barriers to inclusion of biological sex in biomedical studies were failure to collect and analyze samples according to sex, and failure to separate male and female samples from one another during sample collection. Journal policies may represent an effective tool to encourage inclusion of biological sex as a variable. [ABSTRACT FROM AUTHOR]

Although the trajectories of children's social skills have been examined across biological sexes, less research has examined these patterns for racially and ethnically diverse children in the United States. The purpose of this study was to estimate the longitudinal growth trajectories of social skills, while examining the influence of biological sex, race, and ethnic identities using an adaptation of the commonly used Social Skills Rating Scale. A large nationally representative sample of elementary school children in the United States were assessed annually from kindergarten through fifth grade (N = 11,792). Structural equation modeling was used to examine latent growth curve models of teacher‐rated interpersonal skills and self‐control. After finding evidence of longitudinal invariance, results suggested a quadratic growth pattern best represented the trajectories of social skills ratings. Teacher ratings for African American children demonstrated a moderate declining linear trajectory throughout elementary school when compared with White children (reference group) and their Asian and Hispanic peers. Children from families with higher socioeconomic status and girls showed moderate to large differences in social skills ratings in kindergarten and stronger growth across time. Implications of the findings with future directions for research are discussed. Practitioner Points: Teacher ratings of children's social skills differ by child demographics.Teacher ratings for African American children show a decline throughout elementary school compared to peers.Children from families with higher socioeconomic status and girls showed larger differences and stronger growth. [ABSTRACT FROM AUTHOR]