scholarly journals Reporting and misreporting of sex differences in the biological sciences

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Yesenia Garcia-Sifuentes ◽  
Donna L Maney
Keyword(s):  
Biological Sciences ◽  
Sex Differences ◽  
Biomedical Research ◽  
Specific Effect ◽  
National Institutes Of Health ◽  
Specific Effects ◽  
Biological Variable ◽  
Males And Females ◽  
Increasing Risk ◽  
Do So

As part of an initiative to improve rigor and reproducibility in biomedical research, the U.S. National Institutes of Health now requires the consideration of sex as a biological variable in preclinical studies. This new policy has been interpreted by some as a call to compare males and females with each other. Researchers testing for sex differences may not be trained to do so, however, increasing risk for misinterpretation of results. Using a list of recently published articles curated by Woitowich et al. (eLife, 2020; 9:e56344), we examined reports of sex differences and non-differences across nine biological disciplines. Sex differences were claimed in the majority of the 147 articles we analyzed; however, statistical evidence supporting those differences was often missing. For example, when a sex-specific effect of a manipulation was claimed, authors usually had not tested statistically whether females and males responded differently. Thus, sex-specific effects may be over-reported. In contrast, we also encountered practices that could mask sex differences, such as pooling the sexes without first testing for a difference. Our findings support the need for continuing efforts to train researchers how to test for and report sex differences in order to promote rigor and reproducibility in biomedical research.

scholarly journals Reporting and Misreporting of Sex Differences in the Biological Sciences

2021 ◽  
Author(s):  
Yesenia Garcia-Sifuentes ◽  
Donna L Maney
Keyword(s):  
Biological Sciences ◽  
Sex Differences ◽  
Biomedical Research ◽  
Specific Effect ◽  
National Institutes Of Health ◽  
Specific Effects ◽  
Biological Variable ◽  
Males And Females ◽  
Increasing Risk ◽  
Do So

As part of an initiative to improve rigor and reproducibility in biomedical research, the U. S. National Institutes of Health now requires the consideration of sex as a biological variable in preclinical studies. This new policy has been interpreted by some as a call to compare males and females with each other. Researchers testing for sex differences may not be trained to do so, however, increasing risk for misinterpretation of results. Using a list of recently published articles curated by Woitowich et al. (eLife, 2020; 9:e56344), we examined reports of sex differences and non-differences across nine biological disciplines. Sex differences were claimed in the majority of the 147 articles we analyzed; however, statistical evidence supporting those differences was often missing. For example, when a sex-specific effect of a manipulation was claimed, authors usually had not tested statistically whether females and males responded differently. Thus, sex-specific effects may be over-reported. In contrast, we also encountered practices that could mask sex differences, such as pooling the sexes without first testing for a difference. Our findings support the need for continuing efforts to train researchers how to test for and report sex differences in order to promote rigor and reproducibility in biomedical research.

scholarly journals A 10-year follow-up study of sex inclusion in the biological sciences

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Nicole C Woitowich ◽  
Annaliese Beery ◽  
Teresa Woodruff
Keyword(s):  
Biological Sciences ◽  
Biomedical Research ◽  
National Institutes Of Health ◽  
Follow Up Study ◽  
Single Sex ◽  
Biological Variable ◽  
The Us ◽  
The Impact ◽  
Male Subjects

In 2016, to address the historical overrepresentation of male subjects in biomedical research, the US National Institutes of Health implemented a policy requiring investigators to consider sex as a biological variable. In order to assess the impact of this policy, we conducted a bibliometric analysis across nine biological disciplines for papers published in 34 journals in 2019, and compared our results with those of a similar study carried out by Beery and Zucker in 2009. There was a significant increase in the proportion of studies that included both sexes across all nine disciplines, but in eight of the disciplines there was no change in the proportion studies that included data analyzed by sex. The majority of studies failed to provide rationale for single-sex studies or the lack of sex-based analyses, and those that did relied on misconceptions surrounding the hormonal variability of females. Together, these data demonstrate that while sex-inclusive research practices are more commonplace, there are still gaps in analyses and reporting of data by sex in many biological disciplines.

scholarly journals Multifaceted origins of sex differences in the brain

2016 ◽  
Vol 371 (1688) ◽  
pp. 20150106 ◽  
Author(s):  
Margaret M. McCarthy
Keyword(s):  
Sex Differences ◽  
State Of The Art ◽  
Human Subjects ◽  
Special Issue ◽  
Molecular Analyses ◽  
The Past ◽  
Current State ◽  
Biological Variable ◽  
Males And Females ◽  
The Brain

Studies of sex differences in the brain range from reductionistic cell and molecular analyses in animal models to functional imaging in awake human subjects, with many other levels in between. Interpretations and conclusions about the importance of particular differences often vary with differing levels of analyses and can lead to discord and dissent. In the past two decades, the range of neurobiological, psychological and psychiatric endpoints found to differ between males and females has expanded beyond reproduction into every aspect of the healthy and diseased brain, and thereby demands our attention. A greater understanding of all aspects of neural functioning will only be achieved by incorporating sex as a biological variable. The goal of this review is to highlight the current state of the art of the discipline of sex differences research with an emphasis on the brain and to contextualize the articles appearing in the accompanying special issue.

Sensory neurons, neuroimmunity, and pain modulation by sex hormones

Endocrinology ◽  
2021 ◽  
Author(s):  
Melissa E Lenert ◽  
Amanda Avona ◽  
Katherine M Garner ◽  
Luz R Barron ◽  
Michael D Burton
Keyword(s):  
Sex Differences ◽  
Sex Hormones ◽  
Cell Types ◽  
Pain Modulation ◽  
National Institutes Of Health ◽  
Neuron Activity ◽  
Sexually Dimorphic ◽  
Dependent Manner ◽  
Biological Variable ◽  
Different Cell Types

Abstract The inclusion of females in preclinical pain studies has become more commonplace in the last decade, as the National Institutes of Health (NIH) “Sex as a Biological Variable” (SABV) mandate was released. Presumably, basic researchers have not had a comprehensive understanding about neuroimmune interactions in half of the population and how hormones play a role in this. To date, we have learned that sex hormones contribute to sexual differentiation of the nervous system and sex differences in behavior throughout the lifespan; however, the cycling of sex hormones does not always explain these differences. Here, we highlight recent advances in our understanding of sex differences and how hormones and immune interactions influence sensory neuron activity to contribute to physiology and pain. Neuroimmune mechanisms may be mediated by different cell types in each sex, as the actions of immune cells are sexually dimorphic. Unfortunately, the majority of studies assessing neuronal contributions to immune function have been limited to males, so it is unclear if the mechanisms are similar in females. Finally, pathways that control cellular metabolism, like nuclear receptors have been shown to play a regulatory role in both pain and inflammation. Overall, communication between the neuroimmune and endocrine systems modulate pain signaling in a sex-dependent manner, but more research is needed to reveal nuances of these mechanisms.

scholarly journals Sex Difference in Self-Reported Sexual Functioning Among Frail Older Adults

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 313-313
Author(s):  
Brianne Olivieri-Mui ◽  
Sandra Shi ◽  
Ellen McCarthy ◽  
Dae Kim
Keyword(s):  
Older Adults ◽  
Logistic Regression ◽  
Sex Differences ◽  
Sexual Function ◽  
Older Adult ◽  
Sexual Functioning ◽  
Social Life ◽  
Well Being ◽  
Adult Males ◽  
Males And Females

Abstract Frailty may differentially impact how older adult males and females perceive sexual functioning, an important part of well-being. We assessed the level of frailty (robust, pre-frail, frail) for anyone with data on 11 sexual functioning questions asked in wave 2 of the National Social Life, Health, and Aging Project, 2010-2011 (n=2060). Questions covered five domains: overall sexual function (OSF), sexual function anxiety (SFA), changes in sexual function (CSF), erectile/vaginal dysfunction (EVD), and masturbation. Logistic regression identified sex differences in frailty and reporting worse sexual functioning. Linear regression predicted the number of domains reported as worse. Among males (n=1057), pre-frailty meant higher odds of reporting SFA (OR 1.8 95%CI 1.2-6.6), CSF (OR 1.7 95%CI 1.1-2.7), and EVD (OR 1.5 95%CI 1.0-2.2). Among females (n=1003), there was no difference in reporting by frailty. Females were more likely to report worse OSF (Robust: OR 7.4, 95%CI 4.8-11.4; Pre-frail: OR 6.2, 95%CI 3.9-9.9; Frail: OR 3.4 95%CI 1.7-6.6), but less likely to report SFA (Robust OR .3, 95%CI .2-.5; Pre-frail OR .2, 95%CI .1-.3; Frail OR .2 95%CI .1-.3). Pre-frail and frail females reported fewer domains as worse (Pre-frail coefficient -0.21 SE 0.09, Frail -0.43 SE 0.14). As frailty worsened, males reported more domains as worse (Pre-frail 0.24 SE 0.07, Frail 0.29 SE 0.08). Self-reported sexual functioning differs by sex at all levels of frailty, and reporting by males, but not females, changes with frailty. Providers should be aware that sexual functioning is of importance to both sexes despite varying degrees of frailty.

scholarly journals Stem cell treatment improves post stroke neurological outcomes: a comparative study in male and female rats

2021 ◽  
pp. svn-2020-000834
Author(s):  
Koteswara Rao Nalamolu ◽  
Bharath Chelluboina ◽  
Casimir A Fornal ◽  
Siva Reddy Challa ◽  
David M Pinson ◽  
...  
Keyword(s):  
Stem Cells ◽  
Sex Differences ◽  
Motor Function ◽  
Infarct Volume ◽  
Female Rats ◽  
Human Umbilical Cord ◽  
Male And Female ◽  
Post Stroke ◽  
Male And Female Rats ◽  
Males And Females

Background and purposeThe therapeutic potential of different stem cells for ischaemic stroke treatment is intriguing and somewhat controversial. Recent results from our laboratory have demonstrated the potential benefits of human umbilical cord blood-derived mesenchymal stem cells (MSC) in a rodent stroke model. We hypothesised that MSC treatment would effectively promote the recovery of sensory and motor function in both males and females, despite any apparent sex differences in post stroke brain injury.MethodsTransient focal cerebral ischaemia was induced in adult Sprague-Dawley rats by occlusion of the middle cerebral artery. Following the procedure, male and female rats of the untreated group were euthanised 1 day after reperfusion and their brains were used to estimate the resulting infarct volume and tissue swelling. Additional groups of stroke-induced male and female rats were treated with MSC or vehicle and were subsequently subjected to a battery of standard neurological/neurobehavioral tests (Modified Neurological Severity Score assessment, adhesive tape removal, beam walk and rotarod). The tests were administered at regular intervals (at days 1, 3, 5, 7 and 14) after reperfusion to determine the time course of neurological and functional recovery after stroke.ResultsThe infarct volume and extent of swelling of the ischaemic brain were similar in males and females. Despite similar pathological stroke lesions, the clinical manifestations of stroke were more pronounced in males than females, as indicated by the neurological scores and other tests. MSC treatment significantly improved the recovery of sensory and motor function in both sexes, and it demonstrated efficacy in both moderate stroke (females) and severe stroke (males).ConclusionsDespite sex differences in the severity of post stroke outcomes, MSC treatment promoted the recovery of sensory and motor function in male and female rats, suggesting that it may be a promising treatment for stroke.

scholarly journals OP0013 SEX DIFFERENCES IN AUTOIMMUNE DISEASE SUSCEPTIBILITY; A MULTI-OMIC APPROACH

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 8.1-8
Author(s):  
G. Robinson ◽  
K. Waddington ◽  
J. Peng ◽  
A. Radziszewska ◽  
H. Peckham ◽  
...  
Keyword(s):  
Sex Differences ◽  
Lipid Metabolism ◽  
Sex Hormones ◽  
Cell Function ◽  
Immune Cell ◽  
Density Lipoprotein ◽  
Hormone Treatment ◽  
Immune Cell Function ◽  
Immune Cell Subsets ◽  
Males And Females

Background:Males and females have altered immune responses resulting in variation in autoimmune and cardiovascular disease risk (CVR). Recently, these differences have played a role in the inflammatory response to COVID-19. Sex differences exist in the frequency and activity of immune-cell subsets but mechanisms underlying sexual dimorphism remain unknown. Juvenile-onset systemic lupus erythematosus (JSLE) is an autoimmune disorder that commonly emerges during puberty, has a strong female prevalence (female:male ratio, 4.5:1) and results in an increased CVR. JSLE is characterised by chronic inflammation and dyslipidaemia, where cardiovascular disease is a leading cause of mortality for patients. Our previous work identified a link between immune cell function and lipid metabolism in adult-onset SLE. We hypothesised that sex hormones could influence both lipid metabolism and immune cell function and this could determine sex-specific susceptibility to JSLE and associated CVR.Objectives:We investigated the role of sex hormones in modifying systemic lipid metabolism and inflammation.Methods:Nuclear magnetic resonance spectroscopy based serum metabolomics measuring over 130 lipoproteins (14-subsets with lipid compositions), flow cytometry measuring immune-cells, and RNA-sequencing were used to assess the metabolic and immune profile in young, pre/post-pubertal males (n=10/17) and females (n=10/23) and in individuals with gender-dysphoria (GD) under cross-hormone treatment (trans-male/female, n=26/25). This analysis was also performed on a cohort of post-pubertal male (n=12) and female (n=23) JSLE patients. Data was analysed by logistic regression, balanced random forest machine learning (BRF-ML), differential gene expression (DEG) and pathway analysis.Results:Post-pubertal males had significantly reduced cardio-protective high-density lipoprotein (HDL) subsets (p<0.0001) and increased cardio-pathogenic very-low-density lipoprotein subsets (p<0.0001) compared to females. These differences were not observed pre-puberty and were reversed significantly by cross-hormone treatment in GD individuals, suggesting that sex hormones regulate lipid metabolism in-vivo.BRF-ML (28 immune-cell subsets) identified an increased frequency of anti-inflammatory regulatory T-cells (Tregs) in post-pubertal males compared to females (p=0.0097). These Tregs were also more suppressive in males compared to females. Differences in Treg frequency were seen pre-puberty and were not altered by sex hormone treatment in GD individuals. However, Treg DEGs and functional transcriptomic pathways altered between post-pubertal males and females, including those involved in inflammatory signalling, overlapped with those altered by hormones in GD, suggesting hormones may also drive Treg functional changes. In addition, HDL metabolites modified by hormones showed differential associations with Treg phenotypes between post-pubertal males and females.Strikingly, sex differences in lipoproteins and Tregs were lost in JSLE, suggesting hormone signalling could be dysregulated in the pathogenesis of autoimmunity and could increase CVR for patients.Conclusion:Sex hormones drive altered lipoprotein metabolism and functional transcriptomic pathways in Tregs. Males have a lipoprotein profile associated with increased CVR, but a more anti-inflammatory immune profile compared to females. Together, this could explain sex differences in inflammatory disease susceptibilities and inform future sex-specific therapeutic strategies for the management of both JSLE and CVR.Acknowledgements:Lupus UKRosetrees TrustVersus ArthritisNIHR UCLH Biomedical Research CentreDisclosure of Interests:None declared

scholarly journals Alternatives to and Reduction of Animal Use in Biomedical Research, Education and Testing

1990 ◽  
Vol 18 (1_part_1) ◽  
pp. 65-74
Author(s):  
John M. Frazier ◽  
Alan M. Goldberg
Keyword(s):  
Biomedical Research ◽  
Toxicity Testing ◽  
Research Education ◽  
New Methods ◽  
New Approaches ◽  
The Future ◽  
Technological Developments ◽  
Animal Use ◽  
Do So

Biomedical endeavours can be divided into three major categories: research, education, and testing. Within the context of each of these categories, activities involving whole animals have made major contributions and will continue to do so in the future. However, with technological developments in the areas of biotechnology and computers, new methods are already reducing the use of whole animals in certain areas. This article discusses the general issues of alternatives and then focuses on the development of new approaches to toxicity testing.

scholarly journals Sex differences in outcomes after arthroscopic bankart repair

2020 ◽  
Vol 6 (1) ◽  
pp. e000965
Author(s):  
Natalie A Lowenstein ◽  
Peter J Ostergaard ◽  
Daniel B Haber ◽  
Kirsten D Garvey ◽  
Elizabeth G Matzkin
Keyword(s):  
Mental Health ◽  
Sex Differences ◽  
Patient Reported Outcomes ◽  
Strength Function ◽  
Bankart Repair ◽  
Level Of Evidence ◽  
Arthroscopic Bankart Repair ◽  
Patient Reported ◽  
Males And Females

ObjectivesRisk factors for anterior shoulder dislocation include young age, contact activities and male sex. The influence of sex on patient-reported outcomes of arthroscopic Bankart repair (ABR) is unclear, with few studies reporting potential differences. This study’s purpose was to compare patient-reported outcomes of males and females following ABR.MethodsProspectively collected data was analysed for 281 patients (males: 206, females: 75) after ABR with preoperative, 1-year and 2-year follow-up responses. The Wilcoxon signed-rank and χ2 tests, preoperative, 1 year and 2 year follow-up results were examined to determine differences of scores in males versus females.ResultsNo statistically significant sex differences were observed in Simple Shoulder Test (SST), American Shoulder and Elbow Surgeons (ASES), Visual Analogue Scale (VAS) or Single Assessment Numerical Evaluation (SANE) Scores at 1-year or 2-year follow-up. Females had lower Veterans RAND 12-item health survey (VR-12) mental health subscores at 2-year follow-up (females: 52.3±9.0, males: 55.8±7.6, p=0.0016). Females were more likely to report that treatment had ‘exceeded expectations’ at 2-year follow-up regarding motion, strength, function and normal sports activities.ConclusionResults of study demonstrate that ABR has similar outcomes for both males and females. There were no statistically significant sex-related differences in SST, ASES, VAS or SANE scores following ABR. VR-12 mental health subscores showed a minimal difference at 2-year follow-up, with lower scores in females.Level of evidenceRetrospective cohort study; level II.

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