Sex-based Differences Research Articles

The influence of patient sex on pulmonary embolism evaluation, treatment modality, and outcomes.

Pulmonary embolism (PE) is the third-leading cause of cardiovascular mortality, accounting for 100,000 deaths per year in the United States. Although sex-based disparities have previously been described in this population, it is unclear if these differences have persisted with the expansion of PE evaluation and treatment approaches. The purpose of this study is to investigate sex-based differences in the evaluation, management, and outcomes of patients with acute PE. We performed a retrospective analysis of patients enrolled in the national Pulmonary Embolism Response Team (PERT) Consortium database between October 2015 and October 2022. We evaluated patient demographics, clinical characteristics, diagnostic imaging performed, treatment at several phases of care (pre-PERT, PERT recommendations, and post-PERT), and clinical outcomes. A total of 5722 patients with acute PE (2838 [49.6%] women) from 35 centers were included. There were no differences in PE risk category between male and female patients. Women were less likely to undergo echocardiography (76.9% vs 73.8%) and more likely to receive no anticoagulation prior to PERT evaluation (35.5% vs 32.9%). PERT teams were more likely to recommend catheter-based interventions for men (26.6% vs 23.1%), and men were more likely to undergo these procedures (21.9% vs 19.3%). In a multivariable analysis, female sex was a predictor of in-hospital mortality (OR 1.53, 95% CI 1.06 to 2.21). In this analysis, we identified sex-based differences in the evaluation and management of patients presenting with acute PE. Subsequently, women presenting with acute PE were at higher risk of in-hospital mortality.

Sex and gender reporting in UK emergency medicine trials from 2010 to 2023: a systematic review

BackgroundFemale participants are underrepresented in randomised control trials conducted in urgent care settings. Although sex and gender are frequently reported within demographic data, it is less common for primary outcomes...

Role of the X Chromosome in Alzheimer Disease Genetics

The X chromosome has remained enigmatic in Alzheimer disease (AD), yet it makes up 5% of the genome and carries a high proportion of genes expressed in the brain, making it particularly appealing as a potential source of unexplored genetic variation in AD. To perform the first large-scale X chromosome-wide association study (XWAS) of AD. This was a meta-analysis of genetic association studies in case-control, family-based, population-based, and longitudinal AD-related cohorts from the US Alzheimer's Disease Genetics Consortium, the Alzheimer's Disease Sequencing Project, the UK Biobank, the Finnish health registry, and the US Million Veterans Program. Risk of AD was evaluated through case-control logistic regression analyses. Data were analyzed between January 2023 and March 2024. Genetic data available from high-density single-nucleotide variant microarrays and whole-genome sequencing and summary statistics for multitissue expression and protein quantitative trait loci available from published studies were included, enabling follow-up genetic colocalization analyses. A total of 1 629 863 eligible participants were selected from referred and volunteer samples, 477 596 of whom were excluded for analysis exclusion criteria. The number of participants who declined to participate in original studies was not available. Risk of AD, reported as odds ratios (ORs) with 95% CIs. Associations were considered at X chromosome-wide (P < 1 × 10-5) and genome-wide (P < 5 × 10-8) significance. Primary analyses are nonstratified, while secondary analyses evaluate sex-stratified effects. Analyses included 1 152 284 participants of non-Hispanic White, European ancestry (664 403 [57.7%] female and 487 881 [42.3%] male), including 138 558 individuals with AD. Six independent genetic loci passed X chromosome-wide significance, with 4 showing support for links between the genetic signal for AD and expression of nearby genes in brain and nonbrain tissues. One of these 4 loci passed conservative genome-wide significance, with its lead variant centered on an intron of SLC9A7 (OR, 1.03; 95% CI, 1.02-1.04) and colocalization analyses prioritizing both the SLC9A7 and nearby CHST7 genes. Of these 6 loci, 4 displayed evidence for escape from X chromosome inactivation with regard to AD risk. This large-scale XWAS of AD identified the novel SLC9A7 locus. SLC9A7 regulates pH homeostasis in Golgi secretory compartments and is anticipated to have downstream effects on amyloid β accumulation. Overall, this study advances our knowledge of AD genetics and may provide novel biological drug targets. The results further provide initial insights into elucidating the role of the X chromosome in sex-based differences in AD.

Sex-Specific Cytokine, Chemokine, and Growth Factor Signatures in T1D Patients and Progressors.

While studies have reported altered levels of cytokines in type 1 diabetes (T1D) patients, the results are inconsistent, likely because of variable factors. This study tests the hypothesis that there are sex-based differences in cytokine levels in T1D, prior to and after disease onset. We analyzed 48 blood cytokine, chemokine, and growth factor levels using a multiplex assay. We found only two cytokines, M-CSF and IL-6, with significant differences between T1D patients (n=25) versus controls overall (n=25). However, we identified notable alterations when comparing sex-age-matched controls and T1D samples. Inflammatory cytokines (TNF-α, IL-6, IL-1a), Th2 cytokines (IL-4, IL-13), and chemokines (MIP-1α, RANTES, MIP-3) were lower in female T1D patients compared to female controls, but not in males. IL-22 was lower in female T1D patients compared to female controls, while it was higher in male T1D patients compared to male controls. In contrast, growth factors (EGF, PDGF-AB/BB) were higher in male T1D patients compared to male controls. In T1D progressors (children who developed the disease years after the sample collection, n=16-21), GROa was lower compared to controls in both sexes. Our findings underscore the importance of understanding sex-specific differences in T1D pathogenesis and their implications for developing personalized treatments.

Sex and Size Disparities in Access to Liver Transplant for Patients With Hepatocellular Carcinoma.

Women on the liver transplant waiting list are less likely to undergo a transplant than men. Recent approaches to resolving this disparity have involved adjustments to Model for End-Stage Liver Disease (MELD) scoring, but this will not affect candidates who rely on exception scores rather than calculated MELD score, the majority of whom have hepatocellular carcinoma (HCC). To evaluate the association between female sex, candidate size, and access to liver transplant among wait-listed patients with HCC. This retrospective cohort study used US transplant registry data of all adult (aged ≥18 years) wait-listed liver transplant candidates receiving an HCC exception score between January 1, 2010, and March 2, 2023. Wait-listed liver transplant candidate sex. The association of female sex with (1) deceased-donor liver transplant (DDLT) and (2) death or waiting list removal for health deterioration were estimated using multivariable competing-risks regression. Results with and without adjustment for candidate height and weight (mediators of the sex disparity) were compared. The cohort included 31 725 candidates with HCC (mean [SD] age at receipt of exception, 61.2 [7.1] years; 76.3% men). Compared with men, women had a lower 1-year cumulative incidence of DDLT (50.8% vs 54.0%; P < .001) and a higher 1-year cumulative incidence of death or delisting for health deterioration (16.2% vs 15.0%; P = .002). After adjustment, without accounting for size, women had a lower incidence of DDLT (subdistribution hazard ratio [SHR], 0.92; 95% CI, 0.89-0.95) and higher incidence of death or delisting (SHR, 1.06; 95% CI, 1.00-1.13) compared with men. When adjusting for candidate height and weight, there was no association of female sex with incidence of DDLT or death or delisting. However, at a height cutoff of 166 cm, short women compared with short men were still less likely to undergo a transplant (SHR, 0.93; 95% CI, 0.88-0.99). In this study, women with HCC were less likely to receive a DDLT and more likely to die while wait-listed than men with HCC; these differences were largely (but not entirely) explained by sex-based differences in candidate size. For candidates listed with exception scores, additional changes to allocation policy are needed to resolve the sex disparity, including solutions to improve access to size-matched donor livers for smaller candidates.

Sex-based differences in candidacy for transcatheter tricuspid valve intervention.

Women have a higher prevalence of tricuspid regurgitation (TR) and present at more advanced stages as compared with men. Given the high operative mortality associated with tricuspid valve (TV) surgery, transcatheter tricuspid valve interventions (TTVI) have emerged as a promising treatment option. We explored sex-based differences among patients with significant TR who would be expected to be eligible for TTVI. Between March 2021-2022, 12,677 unique adult patients underwent a transthoracic echocardiogram at our tertiary care institution. Clinical and echocardiographic data were collected for patients with more than moderate TR. The 2021 European Society of Cardiology valve guidelines were used to retrospectively define sub-populations who would have been eligible for TTVI, TV surgery, or medical therapy. Patients were grouped by sex and compared using t-tests, Wilcoxon rank-sum, Pearson chi-square, and Cox regression for survival analysis. Of 569 patients, 52% (296/569) were female. Men had a higher prevalence of left ventricular dysfunction (p < 0.001), mitral regurgitation (p = 0.023), and signs of heart failure (New York Heart Association stage III (p = 0.031)). Women had more isolated TR (p = 0.020) and TR due to severe pulmonary hypertension (p < 0.001). Most patients (74.6% of women, 76.9% of men) were precluded from both transcatheter and surgical intervention due to advanced disease. 10.8% of women and 9.2% of men would have qualified for TTVI (p = 0.511). The majority of patients with significant TR presenting to a tertiary care center are not eligible for TTVI. Sex is not a predictor of eligibility for TTVI among patients with significant TR.

Prevalence, Symptom Profiles, and Correlates of Mixed Anxiety-Depression in Male and Female Autistic Youth.

Relatively little attention has been given to mixed anxiety and depression in autistic youth, particularly how this differs between males and females. This study investigated sex-based differences in the prevalence and correlates of mixed anxiety and depression in a sample of 51 autistic males (M age = 10.16 yr, SD = 2.81 yr, and range = 6 yr to 17 yr) and 51 autistic females (M age = - 10.07 yr, SD = 2.76 yr, and range = 6 yr to 17 yr), matched for age, IQ, and autism severity. Self-reports on generalised anxiety disorder and major depressive disorder, morning salivary cortisol, ADOS-2 scores, and WASI-II full-scale scores were collected from these autistic youth, and data on the ASD-related symptoms of these youth were collected from their parents. The data were analysed for total anxiety-depression score levels, for the underlying components of this scale, and for the individual items used in the scale. The results indicate no significant sex differences for the prevalence of mixed anxiety and depression total scores or the underlying components of anxiety and depression or for the individual items of the mixed anxiety-depression scale. There were sex differences in the significant correlates of mixed anxiety and depression: morning cortisol and ASD-related difficulties in social interaction for females, and ASD-related behaviour for males. Males' feelings of being restless or edgy were correlated with their social interaction and repetitive and restricted behaviour. Females' difficulties in social interaction were correlated with their concerns about their abilities and their sleeping problems. Females' sleeping problems, their tendency to talk about dying, and feeling worthless, were correlated with their morning cortisol. These findings suggest that, while mixed anxiety and depression is experienced similarly by autistic males and females at the global, component, and individual item levels, specific aspects of the symptomatology of mixed anxiety and depression are differently associated with aspects of their ASD-related symptomatology and their levels of chronic physiological stress for males and females.

Analysis of Prefrontal Cortex Responses According to Oxyhemoglobin Concentration Changes in Participants Undertaking Horticultural Activities

This study aimed to investigate the psychophysiological effects of horticultural activities on the prefrontal cortex (PFC) to understand how horticultural activities can influence mental health and cognitive function. This study involved 39 adults with an average age of 54.6 years (±12.5 years) and was conducted in a laboratory setting at Konkuk University. The impact of five different types of horticultural activities—sowing, transplanting, planting, harvesting, and packaging—on PFC oxyhemoglobin (oxy-HB) concentrations was assessed. Functional near-infrared spectroscopy (fNIRS) was used to measure oxy-HB levels in the PFC while participants engaged in each activity for 90 seconds. The results indicated that the overall PFC oxy-HB concentration was at its lowest during planting and at its highest during sowing (P &lt; 0.001). In the right PFC, oxy-HB was also at its lowest during planting and at its highest during sowing (P &lt; 0.01). In the left PFC, the lowest oxy-HB concentrations were observed during both planting and harvesting, whereas the highest oxy-HB concentrations were observed during transplanting and sowing (P &lt; 0.001). Additionally, sex-based differences were noted, with females showing significantly lower oxy-HB concentrations during sowing (P &lt; 0.05) and transplanting (P &lt; 0.01) than those of males. These findings suggested that psychophysiological responses, as indicated by oxy-HB concentrations, vary depending on the type of horticultural activity and by sex.

Sex-based differences in treatment approaches and outcomes among patients with mpox: Limitations of real-world data.

Limited data on females with mpox restricts understanding of potential sex-based disparities in treatment and outcomes. This study aims to investigate these differences using administrative claims and clinical data repositories. We retrospectively analyzed adults diagnosed with mpox using TriNetX, stratifying cohorts by sex. The primary outcome included urgent care, emergency room, and hospitalization visits, with secondary outcomes including clinical findings, vaccination, and treatment. Among 2011 cases, 90% were male. Males were older, more likely to identify as Hispanic or Latino, and had higher HIV prevalence and sexually transmitted infection rates. Hospitalization rates were low for both groups, with similar healthcare utilization. However, males received fewer opioid analgesics, glucocorticoids, and antiemetics versus females. Vaccination and tecovirimat use were minimal in both groups. Addressing sex disparities in mpox treatment and outcomes is crucial, but existing data sources like administrative claims and clinical data repositories pose limitations.

Unveiling Sex Differences in Pediatric Burns Through the World Health Organization (WHO) Global Burn Registry

IntroductionPediatric burns present a significant global health challenge, particularly in low- and middle-income countries (LMICs). Despite this burden, few studies have explored global sex-based differences in pediatric burns. This study aims to describe pediatric burn incidence, burn care facilities’ capacities, and burn outcomes with a focus on sex, comparing LMICs to HICs. MethodsThis study utilizes the World Health Organization's (WHO) Global Burn Registry (GBR) to analyze pediatric burn cases from 2018 to 2022, examining patient demographics, causes of burns, burn care facilities' capacities, and burn outcomes in relation to sex. Statistical analysis was done by chi-square and logistic regression. ResultsIt was found that female patients were less likely than males to undergo surgical treatment during their hospital stay in low-income countries (adjusted odd ratios = 0.86, 95% CI: 0.45–1.26; p = 0.168) and middle-income countries (adjusted odd ratios = 0.72, 95% Cl: 0.52–0.95; p = 0.002). Additionally, females in both low- (adjusted odd ratios = 2.23, 95% Cl: 1.12–3.53; p = 0.045) and middle-income countries (adjusted odd ratios = 1.72, 95% Cl: 1.12–2.95; p < 0.001) exhibited higher odds of discharging with disability compared to males. ConclusionSex-based differences persist in pediatric burn epidemiology and treatment outcomes. Addressing these differences involves sex-sensitive strategies to mitigate the burden of pediatric burns, particularly in vulnerable populations in low- and middle-income countries. Type of StudyRetrospective observational study. Level of EvidenceLevel III evidence.

Enhanced Ca2+-Driven Arrhythmogenic Events in Female Patients With AtrialFibrillation: Insights From Computational Modeling.

Substantial sex-based differences have been reported in atrial fibrillation (AF), but the underlying mechanisms are poorly understood. This study sought to gain a mechanistic understanding of Ca2+-handling disturbances and Ca2+-driven arrhythmogenic events in male vs female atrial cardiomyocytes and establish their responses to Ca2+-targeted interventions. We integrated reported sex differences and AF-associated changes (ie, expression and phosphorylation of Ca2+-handling proteins, cardiomyocyte ultrastructural characteristics, and dimensions) into our human atrial cardiomyocyte model that couples electrophysiology with spatially detailed Ca2+-handling processes. Sex-specific responses of atrial cardiomyocytes to arrhythmia-provoking protocols and Ca2+-targeted interventions were evaluated. Simulated quiescent cardiomyocytes showed increased incidence of Ca2+ sparks in female vs male myocytes inAF, in agreement with previous experimental reports. Additionally, our female model exhibited elevated propensity to develop pacing-induced spontaneous Ca2+ releases (SCRs) and augmented beat-to-beat variability in action potential (AP)-elicited Ca2+ transients compared with the male model. Sensitivity analysis uncovered distinct arrhythmogenic contributions of each component involved in sex and/or AF alterations. Specifically, increased ryanodine receptor phosphorylation emerged as the major SCR contributor in female AF cardiomyocytes, whereas reduced L-type Ca2+ current was protective against SCRs for male AF cardiomyocytes. Furthermore, simulated Ca2+-targeted interventions identified potential strategies (eg, t-tubule restoration, and inhibition of ryanodine receptor and sarcoplasmic/endoplasmic reticulum Ca2⁺-ATPase) to attenuate Ca2+-driven arrhythmogenic events in women, and revealed enhanced efficacy when applied in combination. Sex-specific modeling uncovers increased Ca2+-driven arrhythmogenic events in female vs male atria inAF, and suggests combined Ca2+-targeted interventions are promising therapeutic approaches in women.

Gender-specific outcomes of low-dose computed tomography screening for lung cancer detection: A retrospective study in Chinese never-smoker population.

Low-dose computed tomography (LDCT) has emerged as a pivotal tool for detecting lung cancer among ever-smokers. This study aims to evaluate the gender-specific outcomes of LDCT screening within the Chinese never-smoking population. We conducted a single-center, retrospective cohort study, which analyzed LDCT screening outcomes for 42,018 asymptomatic participants. Specifically, we focused on assessing gender-specific differences in the prevalence of pulmonary nodules, and the incidence of lung cancer diagnosis among never-smokers. Among the 42,018 eligible participants, 41.50% were females and 58.50% were males. Most participants were non-smokers (77.57%), with a significantly higher proportion of non-smokers among females than males (99.33% vs. 62.14%). Pulmonary nodules were identified in 2.66% of participants, with a higher prevalence in females (2.99%) than males (2.43%) (p < 0.001). Non-smoking females had a higher incidence of positive nodules than non-smoking males (2.98% vs. 2.38%, p < 0.001). Invasive biopsies were performed in 334 individuals with nodules, confirming lung cancer in 258 cases. The majority of these cancer cases were non-smokers (212), with non-smoking females showing a higher incidence (0.85%) compared to males (0.43%) (p < 0.001). There was no significant difference in the false-positive rates between non-smoking females (0.14%) and males (0.13%). Multivariate analysis showed that never-smoking women were more likely to undergo biopsies (OR 1.65, p = 0.0016) and had a higher, though not statistically significant, probability of lung cancer diagnosis (OR 1.84, p = 0.06). This study elucidates sex-based differences within the Chinese population, revealing a higher prevalence of pulmonary nodules and lung cancers among non-smoking females. These findings offer valuable reference for both clinical practice and future research initiatives.

Adherence to guideline-recommended care of late-onset hypertension in females versus males: A population-based cohort study.

Sex-based disparities in cardiovascular outcomes may be improved with appropriate hypertension management. To compare the evidence-based evaluation and management of females with late-onset hypertension compared to males in the contemporary era. Design: Retrospective population-based cohort study. Ontario, Canada. Residents aged ≥66 years with newly diagnosed hypertension between January 1, 2010, and December 31, 2017. Sex (female vs. male). We used Poisson and logistic regression to estimate adjusted sex-attributable differences in the performance of guideline-recommended lab investigations. We estimated adjusted differences in time to the prescription of, and type of, first antihypertensive medication prescribed between females and males, using Cox regression. Among 111,410 adults (mean age 73 years, 53% female, median follow-up 6.8 years), females underwent a similar number of guideline-recommended investigations (adjusted incidence rate ratio, 0.997 [95% confidence interval [CI] 0.99-1.002]) compared to males. Females were also as likely to complete all investigations (0.70% females, 0.77% males; adjusted odds ratio, 0.96 [95% CI 0.83-1.11]). Females were slightly less likely to be prescribed medication (adjusted hazard ratio [aHR] 0.98 [95% CI 0.96-0.99]) or, among those prescribed, less likely to be prescribed first-line medication (aHR, 0.995 [95% CI 0.994-0.997]). Compared to males, females with late-onset hypertension were equally likely to complete initial investigations with comparable prescription rates. These findings suggest that there may be no clinically meaningful sex-based differences in the initial management of late-onset hypertension to explain sex-based disparities in cardiovascular outcomes.

Nutrition and Bone Marrow Adiposity in Relation to Bone Health.

Bone remodeling is energetically demanding process. Energy coming from nutrients present in the diet contributes to function of different cell type including osteoblasts, osteocytes and osteoclasts in bone marrow participating in bone homeostasis. With aging, obesity and osteoporosis the function of key building blocks, bone marrow stromal cells (BMSCs), changes towards higher accumulation of bone marrow adipose tissue (BMAT) and decreased bone mass, which is affected by diet and sex dimorphism. Men and women have unique nutritional needs based on physiological and hormonal changes across the life span. However, the exact molecular mechanisms behind these pathophysiological conditions in bone are not well-known. In this review, we focus on bone and BMAT physiology in men and women and how this approach has been taken by animal studies. Furthermore, we discuss the different diet interventions and impact on bone and BMAT in respect to sex differences. We also discuss the future perspective on precision nutrition with a consideration of sex-based differences which could bring better understanding of the diet intervention in bone health and weight management.

Sex-Based Differences in Frontal Sinus Anatomy: A Cross-Sectional Study

Within the frontal bone of the skull, directly above the eyebrows and behind the forehead, lies an air-filled chamber known as the frontal sinus. Objectives: To investigate sex-based differences in frontal sinus anatomy, including measurements such as height, width, and area. Method: This cross-sectional study was conducted at the Department of Anatomy, Women Medical and Dental College, Abbottabad from January 2023 to December 2023. A total of 300 participants were (N = 300). The participants were divided into two groups: 160 men and 140 women. The participants were physically examined using a radiological process. Results: The female and male mean age of 35.2 ± 18.5 years. The right and left side areas of the frontal sinus were significantly higher in males 77.7% and 82.8%, respectively; p = 0.0001) than in females. Males had a significantly greater height (73.3%) and 75.9 % (p = 0.0001) than females on both sides. It was shown that the right and left side widths in males 79.6% and 74.4% significantly higher, p = 0.0001 as compared to females. Males had more supra agger frontal cells and supraorbital ethmoid cells (78.1% and 81.2%, respectively; p &lt; 0.0001). Conclusions: It was concluded that males have larger frontal sinuses in terms of height, width, area, and ethmoid air cell count than females. These results indicate that males have larger and more developed frontal sinuses than females.

Age-specific sex differences in intravascular ultrasound based coronary atherosclerotic plaque characteristics

Insights in age- and sex-specific coronary atherosclerotic plaque characteristics may contribute to a better understanding of coronary artery disease and, ultimately, to its prevention and treatment. In 307 women and 406 men aged 20 to 90 years undergoing intravascular ultrasound imaging, sex-based differences in coronary atherosclerotic plaque characteristics were mainly present in younger patients, while these differences were less pronounced at advanced age.

Establishing legal threshold of 18-years based on the assessment of mandibular molars using three different methods - An observational study.

The study evaluates the feasibility of employing the radiographic visibility of the root pulp and periodontal ligament in mandibular molars for age estimation, particularly focusing on the 18 years of age threshold. This study additionally investigates the potential of root canal width reduction in mandibular molars, as a reliable method for forensic age estimation in living individuals. A cross-sectional study was conducted to assess the radiographic visibility of the root pulp (RPV) and the root canal width (RCW) of mandibular first, second, and third molars along with the radiographic visibility of the periodontal ligament (PLV) of mandibular third molars, in a sample of 403 individuals aged 16-25 years (220 males and 183 females). Data regarding age for different stages of RPV and PLV and various types of RCW were recorded and observed for sex-based differences. Results obtained were tabulated and descriptive statistics were applied to summarise the findings. Individuals over 18 years old were classified with higher accuracy using stage 3 of the RPV scoring system in all mandibular molars (first, second, and third) compared to stage 2, which was also effective for the second and third molars. This result held regardless of sex and side examined. Additionally, root canal width (RCW) assessment demonstrated that individuals with RCW types A, B, and C were more likely to be under 18 years old in both sexes. Conversely, individuals with RCW type U on the right side for males and the left side for females exhibited a higher likelihood of being above 18 years old. The study suggests that the assessment of mandibular molars could potentially serve as an auxiliary tool in age estimation methods, particularly for approximating individuals around the 18 years of age threshold. Further investigation is warranted to explore the potential application of root canal width measurements in forensic age estimation.

Pressure Cycling Technology Combined With MicroLC-SWATH Mass Spectrometry for the Analysis of Sex-Related Differences Between Male and Female Cerebella: A Promising Approach to Investigating Proteomics Differences in Psychiatric and Neurodegenerative Diseases.

Pressure cycling technology (PCT) coupled with data-independent sequential window acquisition of all theoretical mass spectra (SWATH-MS) can be a powerful tool for identifying and quantifying biomarkers (e.g., proteins) in complex biological samples. Mouse models are frequently used in brain studies, including those focusing on different neurodevelopmental and psychiatric disorders. More and more pieces of evidence have suggested that sex-related differences in the brain impact the rates, clinical manifestations, and therapy outcomes of these disorders. However, sex-based differences in the proteomic profiles of mouse cerebella have not been widely investigated. In this pilot study, we evaluate the applicability of coupling PCT sample preparation with microLC-SWATH-MS analysis to map and identify differences in the proteomes of two female and two male mice cerebellum samples. We identified and quantified 174 proteins in mice cerebella. A comparison of the proteomic profiles revealed that the levels of 11 proteins in the female and male mice cerebella varied significantly. Although this study utilizes a small sample, our results indicate that the studied male and female mice cerebella possessed differing proteome compositions, mainly with respect to energy metabolism processes.

MetaFun: unveiling sex-based differences in multiple transcriptomic studies through comprehensive functional meta-analysis

BackgroundWhile sex-based differences in various health scenarios have been thoroughly acknowledged in the literature, we lack sufficient tools and methods that allow for an in-depth analysis of sex as a variable in biomedical research. To fill this knowledge gap, we created MetaFun as an easy-to-use web-based tool to meta-analyze multiple transcriptomic datasets with a sex-based perspective to gain major statistical power and biological soundness.DescriptionMetaFun is a complete suite that allows the analysis of transcriptomics data and the exploration of the results at all levels, performing single-dataset exploratory analysis, differential gene expression, gene set functional enrichment, and finally, combining results in a functional meta-analysis. Which biological processes, molecular functions or cellular components are altered in a common pattern in different transcriptomic studies when comparing male and female patients? This and other biological questions of interest can be answered with the use of MetaFun. This tool is available at https://bioinfo.cipf.es/metafun while additional help can be found at https://gitlab.com/ubb-cipf/metafunweb/-/wikis/Summary.ConclusionsOverall, Metafun is the first open-access web-based tool to identify consensus biological functions across multiple transcriptomic datasets, helping to elucidate sex differences in numerous diseases. Its use will facilitate the generation of novel biological knowledge that can be used in the research and application of Personalized Medicine considering the sex of patients.

Differences and similarities in patient-reported outcomes among men and women with haemophilia.

Both men and women can be diagnosed with haemophilia and the experience with haemophilia may be different between men and women. This study aimed to compare patient-reported outcomes in men versus women with haemophilia. This cross-sectional study is a post-hoc analysis of data collected as part of the Haemophilia-related Distress Questionnaire validation study. Adults aged ≥18 years with haemophilia A or B were recruited from one of two haemophilia treatment centres between July 2017 and December 2019. Outcomes included quality of life, measures of mental and physical health, and overall health. Unadjusted and multivariable linear regression models were used to examine potential mediators of sex-based differences in outcomes. Of the 139 study participants included (21 women, 118 men), the mean age was 36.9 years and most (89.2%) had haemophilia A. Approximately 85.7% and 26.3% of women and men had mild haemophilia, respectively. PHQ-9 depression and PROMIS-29 Profile anxiety and fatigue scores were significantly higher in women than men in unadjusted and adjusted analyses. There were no statistically significant differences in other outcomes. Women with haemophilia are more likely to experience depression, anxiety, and fatigue than men with haemophilia. This study highlights the need for mental health services to be integrated into the care of women with haemophilia. Future research is needed to understand whether women with haemophilia are more or less likely to experience depression, anxiety, and fatigue than women without haemophilia as well as determine the impact of reduced mental health on clinical outcomes.