Biology of Sex Differences最新文献

{"title":"Sex differences in microvascular patterns associated with low- and high-risk for cardiovascular disease.","authors":"Elin Nyman, Rasmus Magnusson, Tomas Strömberg, Carl Johan Östgren, Sara Bergstrand, Hanna Jonasson","doi":"10.1186/s13293-026-00955-0","DOIUrl":"10.1186/s13293-026-00955-0","url":null,"abstract":"<p><strong>Background: </strong>The role of the microcirculation in cardiovascular health in males and females is not fully understood. Skin microvascular function can be assessed non-invasively by measuring the response to a brief occlusion of the arm, which produces a hyperemic response that depends on multiple regulatory pathways. Whether the resulting time-resolved microvascular parameters discriminate between low- and high-cardiovascular-risk individuals, and whether the informative features differ between males and females, is not known.</p><p><strong>Method: </strong>We analyzed time-resolved skin microcirculatory hemoglobin oxygen saturation and perfusion measured using a combined system integrating laser Doppler flowmetry and diffuse reflectance spectroscopy during a standardized occlusion-release protocol (including baseline, occlusion and reperfusion phases with a total duration of 20 min) in 3,177 participants in the Swedish CArdioPulmonary bioImage Study (SCAPIS) microvascular sub-study. Participants were stratified into a low-risk group (Systematic COronary Risk Evaluation 2 (SCORE2) < 5%, no diabetes or previous atherosclerotic cardiovascular disease (ASCVD); n = 1,645) and a high-risk group (SCORE2 > 7.5%, or diabetes, or previous ASCVD, or severe chronic kidney disease; n = 761). Random forest classifiers were trained to discriminate low- from high-risk individuals using the full time-resolved signals, in the combined cohort and separately by sex, with feature importance mapped back to the time axis.</p><p><strong>Results: </strong>The classifier achieved area under the curve (AUC) of 0.685 (95% confidence interval (CI): 0.663-0.707) in the full cohort (i.e. including both females and males). Discrimination was primarily driven by the post-occlusion hyperemic phase of oxygen saturation, with lower responses observed in high-risk individuals compared to low-risk individuals. Sex-stratified models achieved similar performance in females (AUC 0.638, 95% CI: 0.596-0.679) and males (AUC 0.644, 95% CI: 0.628-0.660). In males, both perfusion and oxygen saturation contributed to risk discrimination, with low-risk individuals exhibiting a more pronounced hyperemic perfusion response. In females, discrimination was driven mainly by oxygen saturation, while perfusion responses showed substantial overlap between risk groups and limited discriminatory value.</p><p><strong>Conclusions: </strong>Time-resolved microvascular signals provide information for cardiovascular risk discrimination that differs between males and females. In both sexes, high-risk individuals exhibited an attenuated post-occlusion oxygen saturation response, indicating impaired microvascular reactivity. Perfusion contributed additional discriminatory information in males, but showed limited value in females. These findings suggest that perfusion and oxygen saturation reflect partly different aspects of microvascular regulation, with different relevance to cardiovascular ri","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"17 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13403894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148598383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hormonal status and reproductive life-course states as modulators of women's physiological responses to acute and chronic hypoxia: insights, challenges, and perspectives.","authors":"Ayoub Boulares, Olivier Dupuy, Nicola Luigi Bragazzi, Carina Enéa, Nathalie Delpech, Philippe Connes, Paul Robach, Samuel Vergès, Aurélien Pichon","doi":"10.1186/s13293-026-00954-1","DOIUrl":"https://doi.org/10.1186/s13293-026-00954-1","url":null,"abstract":"<p><p>Hypoxia research has significantly advanced our understanding of how the human body responds to low-oxygen environments, yet women are still frequently studied without adequate consideration of hormonal status or reproductive life-course stage. This review examines the complex interactions between hormonal status across the female life course and the specific physiological responses of women to acute and chronic hypoxia, focusing on the menstrual cycle, hormonal contraception, pregnancy, menopausal status, hormone replacement therapy, gender-affirming hormone therapy, and reproductive health in high-altitude environments. Estrogen and progesterone significantly modulate ventilatory, cardiovascular, hematological, vascular, and muscular/metabolic responses to hypoxia, with distinct effects across different menstrual cycle phases, contraceptive regimens, and life-course states. Menopause introduces additional complexities, as declining hormone levels alter the body's ability to acclimatize to low-oxygen conditions. Additionally, we examine how chronic and lifelong hypoxia impacts reproductive health, including fertility and pregnancy outcomes, in women living at high altitudes, highlighting both physiological adaptations and contextual factors. While current research has made progress, further studies are needed to better understand these sex-specific responses. We propose that future research should integrate stratified approaches, accounting for hormonal status (cycle phase, contraceptive use, pregnancy, HRT, GAHT) and reproductive status, to optimize health and performance recommendations for women exposed to hypoxic environments.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148496967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vaginal microbiomes and their pertinent social context: a microbial ecological review proffering AMR-STI acquisition and emergence.","authors":"Samantha J Webster, Ian E Cock, Carney Matheson, Emma L Sweeney","doi":"10.1186/s13293-026-00953-2","DOIUrl":"https://doi.org/10.1186/s13293-026-00953-2","url":null,"abstract":"<p><strong>Background: </strong>In the landscape of sexual health, sex, gender, and sexuality are inextricably linked and highly relevant to sexually transmitted infections (STIs). Globally, key sexual and reproductive health concerns of women have been associated with the socioeconomic status of their country, indicating that social context bears influence over sexual health outcomes. Further, the increasing prevalence of antimicrobial resistant STIs (AMR-STIs) in the sexual networks of gay and bisexual men-who-have-sex-with-men (GBMSM) suggests an implicit connection between microbiological and social phenomena, although research to date is relatively limited and often fails to reflect the complexity and nuance of sexual networks. Vulval and vaginal microbiome composition may influence STI acquisition and transmission, yet the relationships between composition, microenvironment, and STIs remain largely overlooked, especially in the context of women and gender-diverse people. In this article, we explore the possibility that a combination of social, sexual, and behavioural factors, combined with biological features, shape the microbiological context of STIs within the vaginal microenvironment. MAIN: The human vaginal microbiome (VMB) forms an ecological niche home to a complex ecosystem of microorganisms. The microbial composition of the VMB is diverse between individuals, with variations observed across racial and ethnic groups, and intrapersonal fluctuations linked to a plethora of factors both within and outside of personal control. Importantly, VMB health is a crucial component of wellbeing for people assigned female at birth (AFAB), transgendered women with neovaginas, and their sexual partners. Clinical context also remains important; in Australia, doxycycline prophylaxis (Doxy-PEP) has recently become available to GBMSM networks aimed to protect against the acquisition of STIs. However, Doxy-PEP guidelines exclude AFAB people and fail to specify regarding use among gender diverse individuals. Given the high prevalence of AMR-STIs within GBMSM networks, the impact of this intervention on excluded partners should be thoroughly investigated. Factors in the VMB such as biofilm formation and necessary microbial balance with opportunistic pathogens renders this ecological microbial niche a hypothetically perfect platform for AMR development and emergence within the social context.</p><p><strong>Conclusion: </strong>This review explores the social context of vaginal microbiomes, their potential influence on AMR-STI development, and highlight several important knowledge gaps to benefit from further research.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148444300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-stratified insights into the genetics of brain volumes in late adulthood.","authors":"Édith Breton, Elleke Tissink, Gloria Matte Bon, Dennis van der Meer, Ole A Andreassen, Tobias Kaufmann","doi":"10.1186/s13293-026-00943-4","DOIUrl":"https://doi.org/10.1186/s13293-026-00943-4","url":null,"abstract":"<p><strong>Background: </strong>The prevalence, timing and disease course of mental and neurological disorders vary according to sex, yet the neurogenetic mechanisms underlying sex differences in brain disorders remain poorly understood. While sex chromosomes and hormones contribute to sex differences in brain biology, previous studies suggest a role for autosomal genetic variation as well.</p><p><strong>Methods: </strong>We investigated autosomal genetic associations with brain volumes in 15,740 females and 15,740 males from the UK Biobank, matched for age and scan site, using sex-stratified genome-wide association analyses. We applied a multivariate genome-wide approach (MOSTest) across 257 brain regions and complemented these analyses with region-specific univariate genome-wide association studies.</p><p><strong>Results: </strong>Heritability estimates and genetic correlations were highly similar between females and males in late adulthood, indicating largely shared genetic influences on brain volumes. Many loci reaching genome-wide significance in one sex also showed signal in the other. Gene mapping in these loci yielded a greater total number of brain-volumes associated genes in females than in males. Variability in the number of mapped genes was particularly pronounced in limbic regions such as the insula, cingulate cortex, hippocampus and amygdala.</p><p><strong>Conclusion: </strong>Overall, our findings contribute to a better understanding of autosomal genetic influences on brain volumes in males and females and may inform future studies examining sex variability in neurobiological mechanisms relevant to brain disorders.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148444312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietary pine pollen induces masculinization in Nile tilapia (Oreochromis niloticus, L. 1758) by modulating sex-biased gene expression and steroid hormone profiles.","authors":"Ivan Abaho, Clifford L W Jones, Peter Akoll, Charles Masembe","doi":"10.1186/s13293-026-00950-5","DOIUrl":"https://doi.org/10.1186/s13293-026-00950-5","url":null,"abstract":"<p><strong>Background: </strong>The health and environmental risks associated with using 17-methyltestosterone hormone (MT) to produce all-male tilapia stocks limit the sustainability of aquaculture. As such, plant-based products with the potential to induce masculinisation in tilapia are gaining considerable attention as potentially safe, nature-based alternatives. However, the underlying mechanism for sex change induction by plant products remains unknown. The present study used pine pollen (PP) to study the processes modulating female-to-male sex change in three-day-old all-female Nile tilapia (Oreochromis niloticus).</p><p><strong>Methods: </strong>Experimental fish were fed either a basal diet supplemented with 1,280 mg PP kg^- 1 from 3 to 30 days post-hatch (dph), or the same basal diet incorporated with 60 mg MT kg^- 1 (MT treatment), or the basal diet only (CT treatment. After 30 dph, fish in all treatments were fed only a basal diet up to 120 dph.</p><p><strong>Results: </strong>Histological observations showed that female-to-male sex change occurred between 21 and 45 dph in MT and PP treatments. During this period, gonadal tissue in PP-treated fish progressively shifted from undifferentiated germ cells toward testes dominated by spermatogonia and spermatocytes. In contrast, MT treatment accelerated spermatogenic progression, with gonads exhibiting advanced germ cells, including spermatids and spermatozoa, reflecting complete masculinisation. Conversely, fish in the CT group underwent normal ovarian differentiation between 21 and 30 dph, characterised by ovarian cavity formation and oocyte-like germ cells. These gonadal histological changes were closely related to temporal changes in sex-biased gene expression and steroid hormone profiles. The PP and MT treatments significantly up-regulated male sex gene expression (dmrt1 and amh) and down-regulated female transcripts (cyp19a1a and foxl2), whereas an opposite pattern was observed in the CT group. Correspondingly, sex steroid concentrations (testosterone and 11-ketotestosterone) were also significantly elevated in both PP- and MT-treated fish, consistent with higher proportions of male individuals (PP: 77.8 ± 2.9% and MT: 97.8 ± 1.1%), unlike the CT group, where fish remained all-female with significantly higher 17β-estradiol levels.</p><p><strong>Conclusion: </strong>These findings imply that PP induces female-to-male sex change in Nile tilapia by disrupting the expression of sex-biased genes and, consequently, the androgen-to-estrogen balance. However, further studies are required to enhance the androgenic potency of PP.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148410189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in MASLD-related atherosclerosis: plaque phenotype, vascular dysfunction, and cardiovascular outcomes.","authors":"Mohamad Jamalinia, Ralf Weiskirchen, Amedeo Lonardo","doi":"10.1186/s13293-026-00952-3","DOIUrl":"https://doi.org/10.1186/s13293-026-00952-3","url":null,"abstract":"<p><strong>Background: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major risk factor for atherosclerotic cardiovascular disease (ASCVD). Emerging evidence suggests that the vascular manifestations of MASLD differ substantially between men and women. We therefore hypothesized that the mechanisms, plaque phenotypes, and clinical implications of MASLD-related ASCVD are sex-specific.</p><p><strong>Methods and results: </strong>In this narrative review, we searched PubMed/MEDLINE for studies published up to April 2026 and synthesized current evidence regarding sex differences in MASLD-related atherosclerosis. Available data support a sex-specific vascular paradigm in MASLD. In men, MASLD is more strongly associated with calcified and obstructive coronary atherosclerosis. In contrast, women with MASLD more frequently exhibit non-calcified atherosclerotic phenotypes and functional vascular abnormalities (e.g., endothelial dysfunction, arterial stiffness, and coronary microvascular dysfunction). Importantly, despite lower coronary artery calcium (CAC) burden, women with MASLD experience a disproportionately greater risk of adverse cardiovascular events. Therefore, calcification-centered assessment may inadequately capture ASCVD risk in women with MASLD by failing to identify non-calcified plaque and functional vascular abnormalities. These sex differences are likely mediated by interacting pathobiological and socio-cultural factors, including sex hormones and menopausal transition, adipose tissue distribution, immune-metabolic and inflammatory profiles, genetic susceptibility, and gender influences.</p><p><strong>Conclusion: </strong>MASLD is associated with distinct sex-specific cardiovascular phenotypes that have important clinical implications for ASCVD risk assessment and prevention. Women with MASLD may develop clinically significant ASCVD despite lower CAC burden, supporting a sex- and menopause-aware approach to cardiovascular evaluation. In selected high-risk women, complementary use of multimodality imaging beyond CAC may improve risk stratification and facilitate earlier detection of clinically relevant cardiovascular disease.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in sleep architecture and nocturnal oxygenation across obstructive sleep apnea severity: an observational hospital-based study.","authors":"Meina Wu, Pei Xue, Jinzhu Yan, Christian Benedict","doi":"10.1186/s13293-026-00951-4","DOIUrl":"https://doi.org/10.1186/s13293-026-00951-4","url":null,"abstract":"<p><strong>Background: </strong>Sex differences in obstructive sleep apnea (OSA) may extend beyond the apnea-hypopnea index (AHI), the standard measure of OSA severity, and involve differences in sleep architecture and nocturnal oxygenation. We compared these characteristics between women and men across OSA severity categories in a large Chinese clinical cohort.</p><p><strong>Methods: </strong>This single-center, hospital-based observational study included adults referred for overnight polysomnography at a sleep center in Fujian, China. OSA severity was classified as mild, moderate, or severe according to AHI. Outcomes included total sleep time (TST), sleep stages, sleep fragmentation, nocturnal oxygenation, respiratory event composition, and the relative distribution of oxygen desaturation events between rapid eye movement (REM) and non-REM sleep. Associations between sex, OSA severity, and these outcomes were examined using adjusted generalized linear models.</p><p><strong>Results: </strong>Among 1,632 patients (mean age 57 years; 41.4% women), women exhibited longer TST, a lower proportion of stage N1 sleep, a higher proportion of stage N3 sleep, and lower sleep fragmentation than men, irrespective of OSA severity (all p < .001). Men exhibited a higher proportion of REM sleep than women only in mild OSA (+ 1.46 percentage points, p = .009). Women showed a greater predominance of hypopneas than men in moderate and severe OSA (p = .02 and p < .001, respectively). Women also exhibited lower nadir oxygen saturation (SpO2) values than men across OSA severity categories (p = .001). In addition, women demonstrated a greater predominance of REM-related oxygen desaturation events than men in both moderate and severe OSA (both p < .001).</p><p><strong>Conclusions: </strong>Women and men with similar OSA severity exhibited distinct patterns of sleep architecture, respiratory event composition, and nocturnal oxygenation. These findings suggest that characteristics beyond AHI may provide additional information regarding the physiological expression of OSA, although their clinical relevance remains to be determined.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148395650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-specific electrophysiological and behavioral responses to nitrous oxide in a murine model of neuropathic pain.","authors":"Gemma González-Hernández, Sonia Torres-Sanchez, Daniel Sanchez-Morillo, Tomi Rantamäki, Esther Berrocoso","doi":"10.1186/s13293-026-00945-2","DOIUrl":"https://doi.org/10.1186/s13293-026-00945-2","url":null,"abstract":"<p><p>Chronic pain-depression comorbidity is characterized by sensory hypersensitivity and emotional dysregulation, and has been linked to alterations in prefrontal network connectivity. It represents a major therapeutic challenge due to its pronounced sex differences in symptom manifestation and increased treatment resistance. Nitrous oxide (N₂O), an inhalational anesthetic traditionally used for its analgesic properties, has recently emerged as a potential rapid-acting antidepressant, with evidence suggesting both rapid and sustained antidepressant effects. Here, we evaluated the behavioral and electrophysiological effects of N₂O (50%, 1 h) in adult male and female mice subjected to the chronic constriction injury (CCI) model of neuropathic pain, assessing its potential to simultaneously target nociceptive and affective symptoms, as well as locomotor behavior. N₂O reduced locomotor activity in both sexes, with longer-lasting effects in males. EEG recordings revealed decreased low-frequency spectral power in both sham and CCI animals, with more widespread effects in females. In the acetone test, N₂O produced analgesia in CCI males but no significant effect in females, while stimulus application increased oscillatory EEG activity across groups and sexes. Notably, CCI females showed an attenuated electrophysiological response compared with Sham-Air controls. In sham animals, N₂O reduced post-stimulus power, whereas in CCI mice it restored prefrontal EEG activity, enhancing the electrophysiological responses in both sexes. In the tail suspension test, only CCI males exhibited a prodepressive phenotype, while no antidepressant-like effects were observed in either sex 24 h post-treatment. These findings demonstrate sex-specific behavioral and neurophysiological responses to N₂O, highlighting the importance of incorporating sex as a biological variable in NMDA receptor-targeted interventions.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The male default prevails in biomedical research: sex inclusion in Nature (2025).","authors":"Ashlyn Swift-Gallant, Liisa A M Galea, Lindsay S Cahill","doi":"10.1186/s13293-026-00947-0","DOIUrl":"https://doi.org/10.1186/s13293-026-00947-0","url":null,"abstract":"<p><p>Despite longstanding recognition of sex as a biological variable, its integration into biomedical research remains inconsistent. Numerous publishers have introduced policies to improve reporting and inclusion of sex and gender, including Nature, which requires authors to complete a Life Science Reporting Summary documenting sex inclusion. Here, we evaluated the effectiveness of these policies by examining sex inclusion and reporting practices in all original research articles involving humans, vertebrates, or cell lines published in Nature in 2025 (N = 513). Nearly two-thirds of articles included both sexes (62.7%); however, inclusion was often nominal. Of these articles reporting inclusion of both sexes, 33% did not maintain inclusion across experiments, used markedly unbalanced sex ratios (≥ 2:1), or alternated between male- and female-only experiments. Another 45.5% of these articles reporting inclusion of both sexes did not report sample size by sex, so it cannot be ascertained whether sex inclusion was maintained across experiments or balanced by sex. Single-sex studies accounted for approximately one-fifth of articles. While male-only and female-only studies occurred at similar overall rates, male-only studies were more than four times more likely to address conditions affecting both sexes while female-only studies were more likely to address sex-specific conditions (e.g., ovarian cancer). Notably, the policies aimed at improving reporting and inclusion also did not increase analysis by sex; only 7% of articles explicitly analyzed sex as a discovery variable for at least some analyses. These findings suggest that transparency-focused reporting summaries alone are insufficient to ensure sex inclusion and/or meaningful analytical integration of sex (i.e., direct comparison of sexes, rather than using sex as a covariate). As a leading biomedical journal, Nature plays a central role in shaping research norms; without stronger editorial expectations, reporting requirements risk reinforcing male-default assumptions rather than advancing rigor and generalizability.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148395684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Circulating nitric oxide pathway metabolites in heart failure with preserved ejection fraction: a sex-stratified cross-sectional analysis.","authors":"Sophia Marie-Theres Dinges, Edzard Schwedhelm, Flavia Baldassarri, Bernhard Haller, Andreas B Gevaert, Rainer Böger, Ephraim B Winzer, Frank Edelmann, Ulrik Wisløff, Volker Adams, Burkert Pieske, Emeline M Van Craenenbroeck, Martin Halle, Susanna M Hofmann, Stephan Mueller-Stegner","doi":"10.1186/s13293-026-00944-3","DOIUrl":"10.1186/s13293-026-00944-3","url":null,"abstract":"","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"17 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13335291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148395633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}