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Abstract Pulmonary arterial hypertension affects females more frequently than males, and there are known sex‐related differences in the lungs. However, normal sex‐related differences in pulmonary vascular structure remain incompletely described. We aimed to contrast computed tomography‐derived pulmonary vascular volume and its distribution within the lungs of healthy adult females and males. From the CanCOLD Study, we retrospectively identified healthy never‐smokers. We analyzed full‐inspiration computed tomography images, using vessel and airway segmentation to generate pulmonary vessel volume, vessel counts, and airway counts. Vessels were classified by cross‐sectional area >10, 5–10, and 10 mm2 (14 ± 8 vs. 27 ± 9 mL), vessel volume 5–10 mm2 (35 ± 11 vs. 55 ± 10 mL), and vessel volume 10 mm2 (11 ± 4 vs. 16 ± 4%, p

Abstract Background Due to sex‐specific differences in the incidence and clinical and histopathological characteristics of colorectal cancer (CRC), understanding the impact of sex on CRC may suggest sex‐targeted strategies for screening, treatment, and prevention, leading to improved prognosis of CRC. However, there have been few studies investigating the sex‐specific differences in CRC in the Republic of Korea. We aimed to assess sex differences in CRC in the Republic of Korea. Methods This was a retrospective, multicenter, cohort study of patients diagnosed with CRC between January 2012 and December 2013 at nine hospitals. Patients who had an uncertain CRC stage, were diagnosed with other cancers within 5 years, had carcinoma in situ, non‐epithelial cancer, or primary cancer other than CRC, were excluded. Factors associated with overall survival or progression‐free survival were investigated using Cox regression analysis. Cumulative probability of metachronous lesions was compared using the Kaplan–Meier estimator survival analysis and we compared the survival curves of each group using a log‐rank test. Outcomes were compared using the chi‐square, Fisher's exact, or Student's t‐test, as appropriate. Results Three thousand one hundred and forteen patients (1999 men, 1315 women) were included. There was no significant difference in the age at onset between men and women. The proportion of patients diagnosed through regular health check‐ups, and asymptomatic at time of diagnosis, was higher in men (48.9% men vs. 42.0% women, p

Background Lower cerebral blood flow (CBF) has previously been documented preoperatively in neonates with congenital heart disease (CHD). However, it remains unclear if these CBF deficits persist over the life span of CHD survivors following heart surgery. When exploring this question, it is critical to consider the sex differences in CBF that emerge during adolescence. Therefore, this study aimed to compare global and regional CBF between postpubertal youth with CHD and healthy peers and examine if such alterations are related to sex. Methods and Results Youth aged 16 to 24 years who underwent open heart surgery for complex CHD during infancy and age‐ and sex‐matched controls completed brain magnetic resonance imaging, including T1‐weighted and pseudo‐continuous arterial spin labeling acquisitions. Global gray matter CBF and regional CBF in 9 bilateral gray matter regions were quantified for each participant. Compared with female controls (N=27), female participants with CHD (N=25) presented with lower global and regional CBF. In contrast, there were no differences in CBF between male controls (N=18) and males with CHD (N=17). Concurrently, female controls had higher global and regional CBF compared with male controls, with no differences in CBF between female and male participants with CHD. CBF was lower in individuals with a Fontan circulation. Conclusions This study provides evidence of altered CBF in postpubertal female participants with CHD despite undergoing surgical intervention during infancy. Alterations to CBF could have implications for later cognitive decline, neurodegeneration, and cerebrovascular disease in women with CHD.

Background: Alpha-synucleinopathies, such as Parkinson's disease (PD), Parkinson's disease dementia (PDD), and dementia with Lewy bodies (DLB), demonstrate sex differences with regard to prevalence, age of onset, and motor manifestations. Neuropsychiatric symptoms (NPS) are common early and late manifestations of these disorders., Objectives: We aimed to describe sex differences in NPS across alpha-synucleinopathies., Methods: We searched Web of Science Core collection databases to identify observational studies published between January 1, 2000, and June 1, 2022, reporting the prevalence or severity of NPS among individuals with a diagnosis of PD, PDD, or DLB. Prevalence and severity were pooled for each NPS according to sex using random-effects models., Results: Two-hundred-and-forty studies, representing 796,026 participants (45% females), were included in the meta-analysis. Female sex was associated with a higher prevalence of anxiety (OR = 1.60 [95% CI: 1.40, 1.82]), depression (OR = 1.56 [1.45, 1.67]), fatigue (OR = 1.21 [1.02, 1.43]), and psychotic symptoms (OR = 1.26 [1.14, 1.40]) and more severe anxiety (g = 1.35 [95% CI: 0.58, 2.13]), depression (g = 1.57 [1.05, 2.08]), and fatigue (g = 0.86 [0.41, 1.32]), while male sex was associated with a higher prevalence of apathy (OR = 0.77 [0.63, 0.93]), impulse control disorders (OR = 0.67 [0.55, 0.82]), REM sleep behavior disorder (OR = 0.54 [0.42, 0.70]), hypersomnolence (OR = 0.67 [0.56, 0.80]), and suicide (OR = 0.30 [0.20, 0.44])., Conclusions: NPS have different prevalences and severities in alpha-synucleinopathies according to sex. These findings support consideration of sex in the elaboration of clinical tools., (© 2024 The Author(s). Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Objective: To determine sex differences in clinical profiles and treatment outcomes in patients with spontaneous intracranial hypotension., Background: Spontaneous intracranial hypotension is associated with considerable functional disability and potentially fatal complications, and it is uncertain whether males and females should be managed differently., Methods: This was a cohort study of consecutive patients with spontaneous intracranial hypotension enrolled from a medical center. Medical records and imaging findings were reviewed. The outcome of treatment responses to epidural blood patches and risks of subdural hematoma were measured., Results: In total, 442 patients with spontaneous intracranial hypotension (165 males, 277 females) were included in the analysis. Males were more likely to have a delayed (>30 days) initial presentation than females (32.1% [53/165] vs. 19.9% [55/277], p = 0.004), and males were less likely to have nausea (55.8% [92/165] vs. 67.1% [186/277], p = 0.016), vomiting (43.0% [71/165] vs. 54.2% [150/277], p = 0.024), photophobia (9.7% [16/165] vs. 17.0% [47/277], p = 0.034), and tinnitus (26.7% [44/165] vs. 39.7% [110/277], p = 0.005) compared with females despite comparable radiologic findings. Among the 374 patients treated with epidural blood patches, males were more likely to be nonresponders to the first epidural blood patch (58.0% [80/138] vs. 39.0% [92/236], OR = 2.2, 95% CI = 1.4-3.3, p < 0.001). Males were at a higher risk of having subdural hematoma (29.7% [49/165] vs. 10.8% [30/277], OR = 3.5, 95% CI = 2.1-5.8, p < 0.001). Among patients with subdural hematoma, males had greater thickness (12.8 ± 4.3 vs. 8.1 ± 5.9 mm, p < 0.001) and were more likely to receive surgical drainage (55.1% [27/49] vs. 10.0% [3/30], OR = 11.0, 95% CI = 3.0-41.3, p < 0.001) than females., Conclusion: In the present study, spontaneous intracranial hypotension in males was characterized by a delayed presentation, poorer response to the first epidural blood patch, and a higher risk of subdural hematoma. Caution should be exercised in the management of males with spontaneous intracranial hypotension. The generalizability of the findings needs to be further confirmed., (© 2024 The Author(s). Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.)

Background and Purpose: New psychoactive substances such as N-ethylpentylone (NEP) are continuously emerging in the illicit drug market, and knowledge of their effects and risks, which may vary between sexes, is scarce. Our present study compares some key effects of NEP in male and female mice., Experimental Approach: Psychostimulant, rewarding and reinforcing effects were investigated by tracking locomotor activity, conditioned place preference (CPP) paradigm and through a self-administration (SA) procedure, respectively, in CD1 mice. Moreover, the expression of early genes (C-fos, Arc, Csnk1e, Pdyn, Pp1r1b and Bdnf in addiction-related brain areas) was assessed by qPCR. Finally, serum and brain levels of NEP were determined by UHPLC-MS/MS., Key Results: NEP-treated males experimented locomotor sensitisation and showed higher and longer increases in locomotion as well as higher hyperthermia after repeated administration than females. Moreover, while preference score in the CPP was similar in both sexes, extinction occurred later, and reinstatement was more easily established for males. Female mice self-administered more NEP than males at a higher dose. Differences in early gene expression (Arc, Bdnf, Csnk1e and Ppp1r1b) were found, but the serum and brain NEP levels did not differ between sexes., Conclusion and Implications: Our results suggest that male mice are more sensitive to NEP psychostimulant and rewarding effects. These differences may be attributed to different early gene expression but not to pharmacokinetic factors. Moreover, males appear to be more vulnerable to the hyperthermic effects of NEP, while females might be more prone to NEP abuse., (© 2024 The Author(s). British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Early life, or juvenility, stands out as the most pivotal phase in neurodevelopment due to its profound impact over the long-term cognition. During this period, significant changes are made in the brain's connections both within and between different areas, particularly in tandem with the development of more intricate behaviors. The hippocampus is among the brain regions that undergo significant postnatal remodeling, including dendritic arborization, synaptogenesis, the formation of complex spines and neuron proliferation. Given the crucial role of the hippocampus in spatial memory processing, it has been observed that spatial memory abilities continue to develop as the hippocampus matures, particularly before puberty. The N-methyl-d-aspartate (NMDA) type of glutamate receptor channel is crucial for the induction of activity-dependent synaptic plasticity and spatial memory formation in both rodents and humans. Although extensive evidence shows the role of NMDA receptors (NMDAr) in spatial memory and synaptic plasticity, the studies addressing the role of NMDAr in spatial memory of juveniles are sparse and mostly limited to adult males. In the present study, we, therefore, aimed to investigate the effects of systemic NMDAr blockade by the MK-801 on spatial memory (novel object location memory, OLM) and hippocampal plasticity in the form of long-term potentiation (LTP) of both male and female juvenile rats. Our results show the sex-dimorphic role of NMDAr in spatial memory and plasticity during juvenility, as systemic NMDAr blockade impairs the OLM and LTP in juvenile males without an effect on juvenile females. Taken together, our results demonstrate that spatial memory and hippocampal plasticity are NMDAr-dependent in juvenile males and NMDAr-independent in juvenile females. These sex-specific differences in the mechanisms of spatial memory and plasticity may imply gender-specific treatment for spatial memory disorders even in children., (© 2024 The Author(s). Hippocampus published by Wiley Periodicals LLC.)

Objectives: This study is aimed at evaluating gender differences in neural activity change response to the acupuncture on left Jianyu (LI 15) in healthy volunteers. Methods: Forty healthy volunteers (20 males and 20 females) received 20-min acupuncture on left LI 15 and underwent functional magnetic resonance imaging (fMRI) scans before and after acupuncture. Amplitude of low-frequency fluctuations (ALFF) in the 0.01-0.08 Hz range were determined for both scans. Paired t -tests were performed on ALFF between two scans separately for the male and female groups to identify neural changes related to acupuncture. Results: After acupuncture, males showed significantly increased ALFF in the left cerebellum and right angular gyrus but decreased ALFF in the left precentral gyrus, left inferior occipital gyrus, and right fusiform gyrus. However, the ALFF change in females is almost negligible. Conclusions: Brain functional activity in response to acupuncture on left LI 15 is noticeably different between males and females. This is preliminary evidence that gender may be an important factor for optimal clinically personalized acupuncture therapy for poststroke shoulder pain in the future., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Guoyan Li et al.)

The mammalian order Primates is known for widespread sexual dimorphism in size and phenotype. Despite repeated speculation that primate sexual size dimorphism either facilitates or is in part driven by functional differences in how males and females interact with their environments, few studies have directly assessed the influence of sexual dimorphism on performance traits. Here, we use a theoretical morphology framework to show that sexual dimorphism in primate crania is associated with divergent biomechanical performance traits. The degree of dimorphism is a significant covariate in biomechanical trait divergence between sexes. Males exhibit less efficient but stiffer cranial shapes and significant evolutionary allometry in biomechanical performance, whereas females maintain performance stability across their size spectrum. Evolutionary rates are elevated for efficiency in females whereas males emphasize size-dependent cranial stiffness. These findings support a hypothesis of sex-linked bifurcation in masticatory system performance: larger male crania and faster size evolution partially compensate for low efficiency and reflect a de-emphasis of mechanical leverage, whereas female crania maintain higher mechanical efficiency overall and evolve more rapidly in molar-based masticatory performance. The evolutionary checks-and-balances between size dimorphism and cranial mechanical performance may be a more important driver of primate phenotypic evolution than has been hitherto appreciated., (© 2024 The Author(s). Journal of Morphology published by Wiley Periodicals LLC.)

Background and Purpose: Relapse presentation in relapsing multiple sclerosis (RMS) differs between sexes, leading to differential outcomes. An influence of age seems likely but is less well investigated separately for women and men., Methods: Using the large well-defined dataset of the pivotal trials of ocrelizumab in RMS, OPERA I and II, and their open-label extension, we performed a post hoc analysis to investigate relapse phenotypes for sex- and age-related differences in n = 929 relapses in 534 subjects (171 men, 363 women). Frequencies of affected functional systems were analyzed separated by sex and for three age strata (<35, 35-44, ≥45 years). Exact p-values are given for this exploratory analysis., Results: Frequencies of mono- versus polysymptomatic relapse presentations were different neither between sexes nor in different age groups. Cerebellar symptoms were more frequent in relapses in men (female [f]: 23.1%, male [m]: 33.0%, p = 0.002), and women's relapses included more sensory (f: 53.8%, m: 32.3%, p < 0.001) and fatigue symptoms (f: 22.6%, m: 14.7%, p = 0.006). Whereas the sex difference for sensory involvement was present over all age groups (<35 years: f: 58.3%, m: 30.4%, p < 0.001; 35-44 years: f: 53.7%, m: 36.0%, p = 0.003; ≥45 years: f: 47.8%, m: 28.8%, p = 0.009), the difference for cerebellar involvement diminished with age (<35 years: f: 20.1%, m: 33.3%, p = 0.009; 35-44 years: f: 22.7%, m: 34.2%, p = 0.034; ≥45 years: f: 27.8%, m: 30.3%, p = 0.750). Relapse presentation seemed to shift with age in women only., Conclusions: We describe sex-specific relapse presentations and an influence of age only for women. Underlying causal factors warrant further investigations., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Pulmonary arterial hypertension affects females more frequently than males, and there are known sex-related differences in the lungs. However, normal sex-related differences in pulmonary vascular structure remain incompletely described. We aimed to contrast computed tomography-derived pulmonary vascular volume and its distribution within the lungs of healthy adult females and males. From the CanCOLD Study, we retrospectively identified healthy never-smokers. We analyzed full-inspiration computed tomography images, using vessel and airway segmentation to generate pulmonary vessel volume, vessel counts, and airway counts. Vessels were classified by cross-sectional area >10, 5-10, and <5 mm 2 into bins, with volume summed within each area bin and in total. We included 46 females and 36 males (62 ± 9 years old). Females had lower total lung volume, total airway counts, total vessel counts, and total vessel volume (117 ± 31 vs. 164 ± 28 mL) versus males (all p  < 0.001). Females also had lower vessel volume >10 mm 2 (14 ± 8 vs. 27 ± 9 mL), vessel volume 5-10 mm 2 (35 ± 11 vs. 55 ± 10 mL), and vessel volume <5 mm 2 (68 ± 18 vs. 82 ± 19 mL) (all p  < 0.001). Normalized to total vessel volume, vessel volume >10 mm 2 (11 ± 4 vs. 16 ± 4%, p  < 0.001) and 5-10 mm 2 (30 ± 6 vs. 34 ± 5%, p  = 0.001) remained lower in females but vessel volume <5 mm 2 relative to total volume was 18% higher (59 ± 8 vs. 50 ± 7%, p  < 0.001). Among healthy older adults, pulmonary vessel volume is distributed into smaller vessels in females versus males., (© 2024 The Authors. Pulmonary Circulation published by Wiley Periodicals LLC on behalf of the Pulmonary Vascular Research Institute.)

The plains vizcacha, Lagostomus maximus, is the only living species in the genus, being notably larger than fossil congeneric species, such as Lagostomus incisus, from the Pliocene of Argentina and Uruguay. Here, we compare the skull growth allometric pattern and sexual dimorphism of L. maximus and L. incisus, relating shape and size changes with skull function. We also test whether the ontogenetic trajectories and allometric trends between both sexes of L. maximus follow the same pattern. A common allometric pattern between both species was the elongation of the skull, a product of the lengthening of rostrum, and chondrogenesis on the spheno-occipitalis synchondrosis and coronalis suture. We also detected a low proportion of skull suture fusion. In some variables, older male specimens did not represent a simple linear extension of female trajectory, and all dimorphic traits were related to the development of the masticatory muscles. Sexual dimorphism previously attributed to L. incisus would indicate that this phenomenon was present in the genus since the early Pliocene and suggests social behaviors such as polygyny and male-male competition. Ontogenetic changes in L. incisus were similar to L. maximus, showing a conservative condition of the genus. Only two changes were different in the ontogeny of both species, which appeared earlier in L. incisus compared to L. maximus: the development of the frontal process of the nasals in a square shape, and the straight shape of the occipital bone in lateral view. Juveniles of L. maximus were close to adult L. incisus in the morphospace, suggesting a peramorphic process. The sequence of suture and synchondroses fusion showed minor differences in temporozygomatica and frontonasalis sutures, indicating major mechanical stress in L. maximus related to size. We suggest a generalized growth path in Chinchillidae, but further analyses are necessary at an evolutionary level, including Lagidium and Chinchilla., (© 2024 Wiley Periodicals LLC.)

There has been extensive evidence that aging affects human brain function. However, there is no complete picture of what brain functional changes are mostly related to normal aging and how aging affects brain function similarly and differently between males and females. Based on resting-state brain functional connectivity (FC) of 25,582 healthy participants (13,373 females) aged 49-76 years from the UK Biobank project, we employ deep learning with explainable AI to discover primary FCs related to progressive aging and reveal similarity and difference between females and males in brain aging. Using a nested cross-validation scheme, we conduct 4200 deep learning models to classify all paired age groups on the main data for females and males separately and then extract gender-common and gender-specific aging-related FCs. Next, we validate those FCs using additional 21,000 classifiers on the independent data. Our results support that aging results in reduced brain functional interactions for both females and males, primarily relating to the positive connectivity within the same functional domain and the negative connectivity between different functional domains. Regions linked to cognitive control show the most significant age-related changes in both genders. Unique aging effects in males and females mainly involve the interaction between cognitive control and the default mode, vision, auditory, and frontoparietal domains. Results also indicate females exhibit faster brain functional changes than males. Overall, our study provides new evidence about common and unique patterns of brain aging in females and males., (© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.)

Altered shape of the proximal femur (cam morphology) or acetabulum (pincer morphology) is indicative of femoroacetabular impingement, which can result in hip pain and osteoarthritis of the hip. As mechanical load during growth affects the resulting bone shape, there is strong evidence in males that cam morphology develops during skeletal growth while physes are open, rather than as an adaptation after growth plates are closed (skeletal maturity). This adaptation is particularly evident in athletes who participate at elite levels prior to skeletal maturity. The research providing this evidence, however, has primarily focused on male athletes. Despite the lack of inclusion in the research, females consistently comprise two thirds of the clinical and surgical populations with structural hip pain or pathology. Knowledge gained from male-dominated cohorts may not appropriately transfer to female athletes, especially at the hip. This perspectives article briefly reviews differences between females and males in femoral and acetabular structure, hormones, timing of puberty/maturation, hypermobility, activity level and movement control-factors which affect hip structure development and loading. Without female-focused research, the application of research findings from male athletes to female athletes may lead to ineffective or even inappropriate recommendations and treatments. Thus, there is a critical need for investment in research to promote life-long hip health for females., (© 2024 Orthopaedic Research Society.)

Background: Women are more likely to experience multiple overlapping pain conditions (MOPCs) relative to men. Post-traumatic stress disorder can negatively impact the severity and trajectory of chronic pain and its treatment. Specific associations between gender, post-traumatic stress disorder (PTSD), and MOPCs require further examination., Methods: A cohort of all Veterans in 2021 who met criteria for one or more of 12 chronic pain types was created using national Veterans Health Administration administrative data. MOPCs were defined as the number of pain types for which each patient met criteria. Multivariable logistic regression models estimated gender differences in frequency for each of the 12 pain subtypes, after controlling for demographics and comorbidities. Negative binomial regression was used to estimate gender differences in the count of MOPCs and to explore moderation effects between gender and PTSD., Results: The cohort included 1,936,859 Veterans with chronic pain in 2021, which included 12.5% women. Among those with chronic pain, women Veterans had higher rates of MOPCs (mean = 2.3) relative to men (mean = 1.9): aIRR = 1.31, 95% CI: 1.30-1.32. PTSD also served as an independent risk factor for MOPCs in adjusted analysis (aIRR = 1.23, 95% CI: 1.23-1.24). The interaction term between gender and PTSD was not significant (p = 0.87). Independent of PTSD, depressive disorders also served as a strong risk factor for MOPCs (aIRR = 1.37, 95% CI: 1.36-1.37)., Conclusions: Individuals with MOPCs and PTSD may have complex treatment needs. They may benefit from highly coordinated trauma-sensitive care and integrated interventions that simultaneously address pain and PTSD., Significance: Women were significantly more likely than men to experience MOPCs. PTSD was also significantly, independently, associated with MOPCs. Patients, particularly women, may benefit from tailored interventions that address both trauma and MOPCs., (© 2024 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation ‐ EFIC ®. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Background: Asthma is a heterogeneous disease with distinct prevalence and manifestation between sexes. This study was to identify sex-specific features of asthma via metabolomic analysis of sphingolipids. Methods: Forty-two asthma patients (27 women and 15 men) admitted to the Peking University Third Hospital from January 2015 to December 2015 were enrolled. Peripheral venous blood was collected for metabolomic analysis by targeted liquid chromatography-mass spectrometry. Sex hormones(estradiol, progesterone, testosterone, and androstenedione) and multiple inflammatory factors (periostin, leptin, IgE, IL-4, IL-5, IL-10, IL-13, IL-17A, and IFN-γ) were also assessed. The eosinophil percentage in induced sputum was also detected. All these data were applied to comparative analysis between sexes. Results: Testosterone was negatively related to periostin (ρ = −0.420, P = 0.009) and IL-5 (ρ = −0.540, P = 0.012), while estradiol was positively related to the blood eosinophil percentage (ρ = 0.384, P = 0.025). Among the eighteen species of sphingolipids detected in the 42 patients, five ceramide (Cer) species (Cer16:0, Cer:20:0, Cer22:0, Cer24:0, and Cer26:0) and one sphingomyelin (SM) species (SM38:0) were significantly higher in male than in female patients. Further investigation found that the correlation between Cer20:0 and IL-5 was positive in males (ρ = 0.943, P = 0.005) but negative in females (ρ = −0.561, P = 0.030). Conclusions: Testosterone was negatively correlated with eosinophil inflammatory factors, but estradiol was positively correlated. Male asthma patients had higher ceramide and sphingomyelin levels than female patients. Different sexes had opposite correlations with ceramide and IL-5, respectively, suggesting that therapeutic strategies targeting ceramide should be different between sexes.

Abstract It is unknown whether biological sex influences phenotypes of commercially available human pulmonary artery endothelial cells (HPAECs). Ten lots of commercial HPAECs were used (Lonza Biologics; PromoCell). Five (50%) were confirmed to be genotypically male (SRY+) and five (50%) were confirmed to be female (SRY−). Experiments were conducted between passages five and eight. HPAEC phenotype was confirmed with a panel of cell expression markers. Standard assays for proliferation, migration and tube formation were performed in triplicate with technical replicates, under three treatment conditions (EndoGRO; Sigma‐Aldrich). Apoptosis was assessed by exposing cells treated with complete media or low serum media to hypoxic (1% oxygen) or normoxic (20% oxygen) conditions. Laboratory staff was blinded. The median (range) age of male and female donors from whom the HPAECs were derived was 58 (48–60) and 56 (33–67), respectively. Our results suggest decreased proliferation in genotypically female cells compared with male cells (p = 0.09). With increasing donor age, female cells were less proliferative and male cells were more proliferative (p = 0.001). Female cells were significantly more apoptotic than male cells by condition (p = 0.001). Female cells were significantly more migratory than male cells in complete media but less migratory than male cells under vascular endothelial growth factor enriched conditions (p = 0.001). There are subtle sex‐based differences in the behavior of HPAECs that depend on donor sex and, less so, age. These differences may undermine rigor and reproducibility. Future studies should define whether biological sex is an important regulator of HPAEC function in health and disease.

Background We describe sex‐differential disease patterns and outcomes of >20.6 million cardiovascular emergency department encounters in the United States. Methods and Results We analyzed primary cardiovascular encounters from the Nationwide Emergency Department Sample between 2016 and 2018. We grouped cardiovascular diagnoses into 15 disease categories. The sample included 48.7% women; median age was 67 (interquartile range, 54–78) years. Men had greater overall baseline comorbidity burden; however, women had higher rates of obesity, hypertension, and cerebrovascular disease. For women, the most common emergency department encounters were essential hypertension (16.0%), hypertensive heart or kidney disease (14.1%), and atrial fibrillation/flutter (10.2%). For men, the most common encounters were hypertensive heart or kidney disease (14.7%), essential hypertension (10.8%), and acute myocardial infarction (10.7%). Women were more likely to present with essential hypertension, hypertensive crisis, atrial fibrillation/flutter, supraventricular tachycardia, pulmonary embolism, or ischemic stroke. Men were more likely to present with acute myocardial infarction or cardiac arrest. In logistic regression models adjusted for baseline covariates, compared with men, women with intracranial hemorrhage had higher risk of hospitalization and death. Women presenting with pulmonary embolism or deep vein thrombosis were less likely to be hospitalized. Women with aortic aneurysm/dissection had higher odds of hospitalization and death. Men were more likely to die following presentations with hypertensive heart or kidney disease, atrial fibrillation/flutter, acute myocardial infarction, or cardiac arrest. Conclusions In this large nationally representative sample of cardiovascular emergency department presentations, we demonstrate significant sex differences in disease distribution, hospitalization, and death.

Background Women have been reported to have worse health‐related quality of life (HRQoL) following stroke than men, but uncertainty exists over the reasons for the sex difference. Methods and Results We included all ischemic strokes registered with the BASIC (Brain Attack Surveillance in Corpus Christi) project (May 2010–December 2016), a population‐based stroke study, who completed a 90‐day outcome interview. Information on baseline characteristics was obtained from medical records and in‐person interviews. HRQoL was measured by the 12‐item short‐form Stroke Specific Quality of Life Scale. Multivariable Tobit regression was used to estimate the mean difference in overall HRQoL scores (range, 1–5; higher indicating better HRQoL) between sexes and to identify contributing factors to the differences. We included 1061 cases with complete data on HRQoL and covariates (median age, 67 years; 51% women). In unadjusted analyses, women had poorer overall HRQoL than men (mean difference, −0.26 [95% CI, −0.40 to −0.13]). Contributors to this difference included sociodemographic/prestroke factors (eg, age, race and ethnicity, prestroke function), risk factors/comorbidities (eg, history of stroke, Alzheimer disease/dementia), and initial stroke severity. Sociodemographic/prestroke factors explained 62% of the sex difference (mean difference, −0.08 [95% CI, −0.21 to 0.04]). In a fully adjusted model that included adjustment for all confounding factors, the sex difference was eliminated and became nonsignificant (mean difference, −0.03 [95% CI, −0.16 to 0.09]). Conclusions Poorer HRQoL in women compared with men was observed and explained by the combination of sociodemographic and prestroke factors, including physical function before stroke and stroke severity. The findings suggest potential subgroups of women who might benefit from more targeted interventions before and after stroke to improve HRQoL.

Male and female dioecious plants often show sexual dimorphism, differing in morphological, physiological and life-history traits. Most previous studies have focused on differences between males and females during or after reproduction, paying little attention to the pre-reproductive stages of the individuals. Here we assessed the response of male and female individuals of the dioecious plant Silene latifolia to abiotic stress at different life stages, including pre-reproductive (i.e. seedlings and young plants) and reproductive individuals. We measured growth, resource allocation and discrimination against 13 C under nutrient deficiency, water stress, as well as their interaction. We observed sexual dimorphism in root growth, with female seedlings having longer main roots than male plants. Pre-reproductive male and female plants also responded differently, in terms of root allocation, to nutrient and water availability. At reproduction, females grew more roots than males when water was not limiting. These differences could help explain the female-skewed sex ratios found in natural populations of S. latifolia. We found no evidence of sexual dimorphism in aboveground dry mass, although females had longer leaves than males at the seedling stage. We conclude that sexual dimorphism in S. latifolia may occur not as a consequence of reproduction, but well before it., (© 2024 The Author(s). Plant Biology published by John Wiley & Sons Ltd on behalf of German Society for Plant Sciences, Royal Botanical Society of the Netherlands.)

Secreted protein acidic and rich in cysteine (SPARC) is the most abundant glycoprotein in bone and is thought to play a critical role in bone remodeling and homeostasis. However, the effect of SPARC in relation to gender and exercise on bone quality is not well understood. The purpose of this study was to quantify differences in the structural and biomechanical properties between calvarial and femoral bone from male and female wild-type (WT) and SPARC null (SPARC (-/-) ) mice as well as the ability of exercise to rescue bone health. Male and female WT and transgenic SPARC (-/-) mice were given either a fixed or rotating running wheel for exercise. Bone structural, biomechanical, and morphological parameters were quantified using micro computed tomography, push out testing for the calvaria, three-point flexural testing for the femurs, histological and immunofluorescent staining. Similar reductions in structural and biomechanical strength were observed in both male and female SPARC (-/-) calvaria, most of which were not significantly affected by exercise. In femurs, SPARC (-/-) had a significant effect on structural parameters in both sexes, but was more pronounced in females with some properties being rescued with running. Interestingly, the effect of SPARC (-/-) on bone mineral density was only detected in female SPARC (-/-) mice, not males, and was subsequently rescued with exercise. This study emphasizes the differences between sexes in WT and SPARC (-/-) mice in regard to structural parameters and biomechanical properties. Research into gender differences can help inform and personalize treatment options to more accurately meet patient needs., (© 2024 Orthopaedic Research Society.)

Abstract Aims Women are overrepresented amongst patients with heart failure with preserved ejection fraction (HFpEF); however, the underpinning mechanism for this asymmetric distribution is unclear. Pregnancy represents a potential gender‐specific risk factor for HFpEF. It leads to significant physiological adaption, and increasing parity has been associated with some cardiovascular risk. We sought to examine the relationship between prior parity with the rest and exercise haemodynamic and echocardiographic profile of women with HFpEF. Methods and results Patients referred for assessment of exertional dyspnoea and confirmed to have a haemodynamic and clinical profile consistent with HFpEF were included. Detailed evaluation consisted of rest and exercise right heart catheterization and echocardiography. A socio‐economic and obstetric history was also documented. Fifty‐eight women were assessed and categorized as having either 0–2 births or ≥3 births, dividing the cohort equally. Women with ≥3 births achieved a lower symptom‐limited workload than those with 0–2 births [38 (24–51) vs. 46 (31–68) W, P = 0.04]. Women with ≥3 births had a greater rise in pulmonary capillary wedge pressure indexed to workload with exercise [0.5 (0.3–0.8) vs. 0.3 (0.2–0.5) mmHg/W, P = 0.03], paralleled by a greater rise in right atrial pressure [10 (8–12) vs. 7 (3–11), P = 0.01]. Pulmonary vascular resistance was also higher in women with ≥3 births [1.9 (1.6–2.4) vs. 1.6 (1.4–1.9) mmHg/L/min rest, P = 0.046, and 1.9 (2.4–2.4) vs. 1.4 (1–1.8) mmHg/L/min exercise, P = 0.024]. Left ventricular ejection fraction was lower at rest [60 (57–61) vs. 63 (60–66), P = 0.008] and during exercise [65 (62–67) vs. 68 (66–70), P = 0.038] in women with higher parity. Conclusions Higher parity is associated with greater impairments in multiple physiologic parameters of HFpEF severity in women, including diastolic reserve, pulmonary vascular resistance, and systolic dysfunction.

Only a small number of studies have assessed structural differences between the two hemispheres during childhood and adolescence. However, the existing findings lack consistency or are restricted to a particular brain region, a specific brain feature, or a relatively narrow age range. Here, we investigated associations between brain asymmetry and age as well as sex in one of the largest pediatric samples to date (n = 4265), aged 1-18 years, scanned at 69 sites participating in the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) consortium. Our study revealed that significant brain asymmetries already exist in childhood, but their magnitude and direction depend on the brain region examined and the morphometric measurement used (cortical volume or thickness, regional surface area, or subcortical volume). With respect to effects of age, some asymmetries became weaker over time while others became stronger; sometimes they even reversed direction. With respect to sex differences, the total number of regions exhibiting significant asymmetries was larger in females than in males, while the total number of measurements indicating significant asymmetries was larger in males (as we obtained more than one measurement per cortical region). The magnitude of the significant asymmetries was also greater in males. However, effect sizes for both age effects and sex differences were small. Taken together, these findings suggest that cerebral asymmetries are an inherent organizational pattern of the brain that manifests early in life. Overall, brain asymmetry appears to be relatively stable throughout childhood and adolescence, with some differential effects in males and females., (© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.)

Brain atrophy and cortical thinning are typically observed in people with Alzheimer's disease (AD) and, to a lesser extent, in those with mild cognitive impairment. In asymptomatic middle-aged apolipoprotein ε4 (ΑPOE4) carriers, who are at higher risk of future AD, study reports are discordant with limited evidence of brain structural differences between carriers and non-carriers of the ε4 allele. Alternative imaging markers with higher sensitivity at the presymptomatic stage, ideally quantified using typically acquired structural MRI scans, would thus be of great benefit for the detection of early disease, disease monitoring and subject stratification. In the present cross-sectional study, we investigated textural properties of T1-weighted 3T MRI scans in relation to APOE4 genotype, age and sex. We pooled together data from the PREVENT-Dementia and ALFA studies focused on midlife healthy populations with dementia risk factors (analysable cohort: 1585 participants; mean age 56.2 ± 7.4 years). Voxel-based and texture (examined features: contrast, entropy, energy, homogeneity) based morphometry was used to identify areas of volumetric and textural differences between APOE4 carriers and non-carriers. Textural maps were generated and were subsequently harmonised using voxel-wise COMBAT. For all analyses, APOE4, sex, age and years of education were used as model predictors. Interactions between APOE4 and age were further examined. There were no group differences in regional brain volume or texture based on APOE4 carriership or when age × APOE4 interactions were examined. Older people tended to have a less homogeneous textural profile in grey and white matter and a more homogeneous profile in the ventricles. A more heterogeneous textural profile was observed for females in areas such as the ventricles, frontal and parietal lobes and for males in the brainstem, cerebellum, precuneus and cingulate. Overall, we have shown the absence of volumetric and textural differences between APOE4 carriers and non-carriers at midlife and have established associations of textural features with ageing and sex., (© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.)

Background: Prior studies have indicated that female individuals outnumber male individuals for certain types of dystonia. Few studies have addressed factors impacting these sex differences or their potential biological mechanisms., Objectives: To evaluate factors underlying sex differences in the dystonias and explore potential mechanisms for these differences., Methods: Data from individuals with various types of dystonia were analyzed in relation to sex. Data came from two different sources. One source was the Dystonia Coalition database, which contains predominantly idiopathic adult-onset focal and segmental dystonias. The second source was the MDSGene database, which contains predominantly early-onset monogenic dystonias., Results: The 3222 individuals from the Dystonia Coalition included 71% female participants and 29% male participants for an overall female-to-male ratio (F:M) of 2.4. This ratio varied according to body region affected and whether dystonia was task-specific. The female predominance was age-dependent. Sex did not have a significant impact on co-existing tremor, geste antagoniste, depression or anxiety. In the 1377 individuals from the MDSGene database, female participants outnumbered male participants for some genes (GNAL, GCH1, and ANO3) but not for other genes (THAP1, TH, and TOR1A)., Conclusions: These results are in keeping with prior studies that have indicated female individuals outnumber male individuals for both adult-onset idiopathic and early onset monogenic dystonias. These results extend prior observations by revealing that sex ratios depend on the type of dystonia, age, and underlying genetics., (© 2024 International Parkinson and Movement Disorder Society.)

Testosterone levels sharply rise during the transition from childhood to adolescence and these changes are known to be associated with changes in human brain structure. During this same developmental window, there are also robust changes in the neural oscillatory dynamics serving verbal working memory processing. Surprisingly, whereas many studies have investigated the effects of chronological age on the neural oscillations supporting verbal working memory, none have probed the impact of endogenous testosterone levels during this developmental period. Using a sample of 89 youth aged 6-14 years-old, we collected salivary testosterone samples and recorded magnetoencephalography during a modified Sternberg verbal working memory task. Significant oscillatory responses were identified and imaged using a beamforming approach and the resulting maps were subjected to whole-brain ANCOVAs examining the effects of testosterone and sex, controlling for age, during verbal working memory encoding and maintenance. Our primary results indicated robust testosterone-related effects in theta (4-7 Hz) and alpha (8-14 Hz) oscillatory activity, controlling for age. During encoding, females exhibited weaker theta oscillations than males in right cerebellar cortices and stronger alpha oscillations in left temporal cortices. During maintenance, youth with greater testosterone exhibited weaker alpha oscillations in right parahippocampal and cerebellar cortices, as well as regions across the left-lateralized language network. These results extend the existing literature on the development of verbal working memory processing by showing region and sex-specific effects of testosterone, and are the first results to link endogenous testosterone levels to the neural oscillatory activity serving verbal working memory, above and beyond the effects of chronological age., (© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.)

Osteoporosis is a common skeletal disorder characterized by an imbalance between bone resorption and formation, exhibiting a higher prevalence in women compared with men. While previous studies have primarily focused on genomics and genetics in osteoporosis susceptibility, there is a lack of systematic exploration of sex-specific differences in lipid levels in mouse bone marrow. Multiple reaction monitoring-based liquid chromatography-trandem mass spectrometry (LC-MS/MS) was used to quantify lipidomic profiles in bone marrow samples from three female mice and three male mice. The LC-MS/MS technique based on the multiple reaction monitoring method identified and quantified 184 lipids from 15 lipid classes. The contents of most lipids in the bone marrow cells of female mice were higher than those in male mice, including four polyunsaturated fatty acids, three phospholipids and four sphingolipids. Among all the lipid molecules, lactosylceramide (d18:0/16:0) showed the highest fold change in female mice, while its precursor lipid, glucosylceramide, was the most up-regulated in male mice. This study, focusing on bone marrow lipidomics, elucidates significant sexual dimorphism in lipid levels within bone marrow cells. It provides novel evidence supporting the higher prevalence of osteoporosis in women and enhances our understanding of the connection between sex-specific lipid levels and the risk of osteoporosis., (© 2024 John Wiley & Sons Ltd.)

Background and Purpose: Women with acute ischemic stroke (AIS) are older and have greater preexisting handicap than men. Given that these factors do not fully explain their poorer long-term outcomes, we sought to investigate potential sex differences in the delivery of acute stroke care in a large cohort of consecutive AIS patients., Methods: We analyzed all patients from ASTRAL (Acute Stroke Registry and Analysis of Lausanne) from March 2003 to December 2019. Multivariable analyses were performed on acute time metrics, revascularization therapies, ancillary examinations for stroke workup, subacute symptomatic carotid artery revascularization, frequency of change in goals of care (palliative care), and length of hospital stay., Results: Of the 5347 analyzed patients, 45% were biologically female and the median age was 74.6 years. After multiple adjustments, female sex was significantly associated with higher onset-to-door (adjusted hazard ratio [aHR] = 1.09, 95% confidence interval [CI] = 1.04-1.14) and door-to-endovascular-puncture intervals (aHR = 1.15, 95% CI = 1.05-1.25). Women underwent numerically fewer diagnostic examinations (adjusted odds ratio [aOR] = 0.94, 95% CI = 0.85-1.04) and fewer subacute carotid revascularizations (aOR = 0.69, 95% CI = 0.33-1.18), and had longer hospital stays (aHR = 1.03, 95% CI = 0.99-1.07), but these differences were not statistically significant. We found no differences in the rates of acute revascularization treatments, or in the frequency of change of goals of treatments., Conclusions: This retrospective analysis of a large, consecutive AIS cohort suggests that female sex is associated with unfavorable pre- and in-hospital time metrics, such as a longer onset-to-door and door-to-endovascular-puncture intervals. Such indicators of less effective stroke care delivery may contribute to the poorer long-term functional outcomes in female patients and require further attention., (© 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

The corpus callosum (CC) is a large white matter fiber bundle in the brain and is involved in various cognitive, sensory, and motor processes. While implicated in various developmental and psychiatric disorders, much is yet to be uncovered about the normal development of this structure, especially in young children. Additionally, while sexual dimorphism has been reported in prior literature, observations have not necessarily been consistent. In this study, we use morphometric measures including surface tensor-based morphometry (TBM) to investigate local changes in the shape of the CC in children between the ages of 12 and 60 months, in intervals of 12 months. We also analyze sex differences in each of these age groups. We observed larger significant clusters in the earlier ages between 12 v 24 m and between 48 v 60 m and localized differences in the anterior region of the body of the CC. Sex differences were most pronounced in the 12 m group. This study adds to the growing literature of work aiming to understand the developing brain and emphasizes the utility of surface TBM as a useful tool for analyzing regional differences in neuroanatomical morphometry., (© 2024 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Objectives: The primary objective of this study was to evaluate the prevalence of white matter hyperintensities (WMHs) in patients who experience migraine and compare findings between adult male and female patients. Specific symptoms and comorbidities also were analyzed to determine whether they were associated with WMH prevalence or the sex of patients with migraine. We hypothesized that females would have a higher prevalence of WMHs, experience more frequent and more severe migraine headaches, and be more likely to have certain comorbidities associated with migraine than males., Background: An increased prevalence of WMHs in patients with migraine has been proposed, although this relation is not well-supported by data from population-based MRI studies. The difference in brain morphology between males and females is of research interest, and females in the general population appear to have a higher prevalence of WMHs. Sex differences and various comorbidities in patients with migraine relative to the number of WMHs on brain imaging have not been fully investigated., Methods: This was a cross-sectional study of 177 patients aged 18 years and older with a diagnosis of migraine who were seen in the Lehigh Valley Fleming Neuroscience Institute's Headache Center between January 1, 2000, and January 1, 2017. Patients' baseline characteristics were extracted from electronic medical records, including demographics, review of systems documentation, and brain imaging from MRI. Variables including headache severity, frequency of head pain, insomnia, and comorbidities (anxiety, depression, diabetes, hyperlipidemia, hypertension, and neck pain) also were analyzed for associations with the presence of WMHs., Results: Females were found to have a significantly higher number of WMHs than males (median 3 [IQR: 0-7] vs. 0 [IQR: 0-3], p = 0.023). Patients with WMHs were significantly more likely than those without WMHs to have hypertension (39.8% of patients with WMHs vs. 20.3% without WMHs, p = 0.011), constipation (20.9% vs. 8.3%, p = 0.034), and sleep disorder (55.7% vs. 37.3%, p = 0.022). Females with migraine were significantly more likely to experience constipation than males (20.0% vs. 2.9%, p = 0.015). None of the migraine characteristics studied (frequency, severity, presence of aura) were different between sexes, nor were they significantly associated with the presence of WMHs., Conclusion: This study suggests that females with migraine may be more likely to have WMHs and experience constipation than males with migraine. Migraine frequency and severity were not different between sexes, nor were they significantly associated with the presence of WMHs. The findings of this study do not support a specific etiology of WMH development in individuals with migraine that differs from findings in the general population. Further studies are warranted., (© 2024 American Headache Society.)

Past research suggests that reactions to research on sex differences are often less positive when the findings put men in a better light than women, especially when the lead researcher is a man. The factors underlying this effect, however, are not yet fully understood. The present study aimed to provide the first experimental test of the hypothesis that the key variable is perceived harm to women. Participants (214 men and 219 women) evaluated a bogus popular-science article reporting fictional research finding either a female- or a male-favouring sex difference in intelligence, attributed to either a female or a male lead researcher. To examine the effects of perceived harm, the introduction to the task highlighted either the potential benefits or potential drawbacks of sex-differences research in general. Consistent with past research, participants reacted less positively to the male-favouring difference, especially for male-led research. Consistent with the harm hypothesis, the effect was stronger after highlighting the potential drawbacks of sex-differences research than after highlighting the potential benefits. Our findings suggest that perceptions of harm to women underpin the aversion to male-favouring findings., (© 2024 International Union of Psychological Science.)

Background: Musician's Dystonia (MD) is a task specific, focal dystonia which usually occurs only at the instrument. The pathophysiology is not fully understood, but several risk factors like over-practice and genetic predisposition are known. Interestingly, 80% of those affected are men, which stands in contrast to the gender distribution in other focal dystonias, such as cervical dystonia., Objectives: Our aim was to evaluate the difference in women and men with regard to risk factors leading to MD., Methods: We investigated known risk factors for MD in a large cohort of 364 MD patients by retrospectively collecting data on practice behavior and family history., Results: In line with previous studies, we found a ratio of ~4:1 men to women. Age at onset of MD was significantly lower in women; however, subsequent analysis revealed that it was a positive family history (FH+) and not gender that was associated with a lower age at onset. Furthermore, we found that those with negative family history had accumulated more practice time until onset of MD., Conclusions: These results imply that the earlier age at onset in women did not depend on gender but was due to the higher proportion of a positive family history. In contrast, men were less likely to have a positive family history, suggesting that genetic factors may not be the primary reason for the higher prevalence of MD in men. Instead, differences in practice behaviors between men and women may contribute to this gender disparity., (© 2024 The Authors. Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Background and Purpose: Biological sex is known to have an impact on quality metrics of acute stroke. We aimed to determine whether COVID positivity accentuates this effect and constitutes worse outcome., Methods: The present analysis was based on the Global COVID-19 Stroke Registry, a retrospective, international, cohort study of consecutive ischemic stroke patients receiving intravenous thrombolysis and/or endovascular thrombectomy between 1 March 2020 and 30 June 2021. We investigated differences between the sexes in patient characteristics, acute stroke metrics as well as post-stroke outcome in COVID-positive and COVID-negative stroke patients undergoing acute revascularization procedures., Results: A total of 15,128 patients from 106 centers were recorded in the Global COVID-19 Stroke Registry, 853 (5.6%) of whom were COVID-positive. Overall, COVID-positive individuals were treated significantly slower according to every acute stroke metric compared to COVID-negative patients. We were able to show that key quality indicators in acute stroke treatment were unfavorable for COVID-negative women compared to men (last-seen-well-to-door time + 11 min in women). Furthermore, COVID-negative women had worse 3-month outcomes (3-month modified Rankin Scale score [interquartile range] 3.0 [4.0] vs. 2.0 [3.0]; p < 0.01), even after adjusting for confounders. In COVID-positive individuals no such difference between the sexes, either in acute management metrics or in 3-month outcome, was seen., Conclusion: Known sex-related differences in acute stroke management exist and extend to times of crisis. Nevertheless, if patients were COVID-19-positive at stroke onset, women and men were treated the same, which could be attributed to structured treatment pathways., (© 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Machine learning (ML) approaches are increasingly being applied to neuroimaging data. Studies in neuroscience typically have to rely on a limited set of training data which may impair the generalizability of ML models. However, it is still unclear which kind of training sample is best suited to optimize generalization performance. In the present study, we systematically investigated the generalization performance of sex classification models trained on the parcelwise connectivity profile of either single samples or compound samples of two different sizes. Generalization performance was quantified in terms of mean across-sample classification accuracy and spatial consistency of accurately classifying parcels. Our results indicate that the generalization performance of parcelwise classifiers (pwCs) trained on single dataset samples is dependent on the specific test samples. Certain datasets seem to "match" in the sense that classifiers trained on a sample from one dataset achieved a high accuracy when tested on the respected other one and vice versa. The pwCs trained on the compound samples demonstrated overall highest generalization performance for all test samples, including one derived from a dataset not included in building the training samples. Thus, our results indicate that both a large sample size and a heterogeneous data composition of a training sample have a central role in achieving generalizable results., (© 2024 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Anterior cruciate ligament (ACL) ruptures result in lasting quadriceps dysfunction that contributes to secondary injury risk and development of osteoarthritis. There is evidence of persistent reduced nervous system drive (corticospinal excitability [CSE]) to the quadriceps and sex differences in both quadriceps performance and CSE post-ACL reconstruction (ACLR). The purposes of this study were to investigate the differences in CSE and quadriceps dysfunction after ACLR between sexes and relative to controls. Twenty subjects 4-9 months post-ACLR and 20 age, sex, and activity matched controls participated in this study. Quadriceps performance (peak torque, PT; rate of torque development from onset to 100 ms, RTD100; and RTD from 100 to 200ms, RTD200) and CSE (active motor threshold; slope of the stimulus response (SR) curve, SR curve slope) were measured using an isokinetic dynamometer (HUMAC NORM) and transcranial magnetic stimulation respectively. Significant group differences were found for SR curve slope, PT, RTD100, and RTD200 on the surgical limb. Males after ACLR had higher slopes (higher CSE) than females. Females after ACLR had worse surgical limb quadriceps PT than control males and slower RTD100 and RTD200 than control males and control females. Higher CSE in males after ACLR may point to a potentially adaptive neurological change in males post-ACLR and indicate greater need for novel interventions to address cortical drive in females after ACLR., (© 2023 Orthopaedic Research Society.)

Objective: Women with psoriatic arthritis (PsA) may have reduced tumor necrosis factor inhibitor (TNFi) effectiveness compared to men. We examined sex differences in treatment response and retention rates during 24 months of follow-up among patients with PsA initiating their first TNFi., Methods: Data from patients with PsA across 13 European Spondyloarthritis Research Collaboration Network registries starting their first TNFi were pooled. Logistic regression was used to analyze the association between sex and treatment response using low disease activity (LDA) according to the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) (<3.2) at six months as the primary outcome. Analyses were adjusted for age, country, conventional synthetic disease-modifying antirheumatic drug treatment, and TNFi start year. Retention rates were explored using the Kaplan-Meier estimator., Results: We analyzed the treatment response of 7,679 patients with PsA (50% women) with available data on LDA at six months. At baseline, women and men had similar characteristics, including mean DAS28-CRP (women vs men, 4.4 [SD 1.2] vs 4.2 [SD 1.2]), though patient-reported outcome measures were worse in women. At six months, 64% of women and 78% of men had LDA (relative risk [RR] 0.82; 95% confidence interval [CI] 0.80-0.84). This difference was similar after adjustment (RR 0.83; 95% CI 0.81-0.85). TNFi retention rates were evaluated in 17,842 patients with PsA. Women had significantly lower retention rates than men at all time points (women 79%, 64%, and 50% vs men 88%, 77%, and 64% at 6, 12, and 24 months, respectively)., Conclusion: Despite comparable disease characteristics at baseline, women with PsA have reduced treatment response and retention rates to their first TNFi, highlighting the need to consider sex differences in PsA research and management., (© 2023 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Schizophrenia is a chronic psychiatric disorder with characteristic symptoms of delusions, hallucinations, lack of motivation, and paucity of thought. Recent evidence suggests that the symptoms of schizophrenia, negative symptoms in particular, vary widely between the sexes and that symptom onset is earlier in males. A better understanding of sex-based differences in functional magnetic resonance imaging (fMRI) studies of schizophrenia may provide a key to understanding sex-based symptom differences. This study aimed to summarize sex-based functional magnetic resonance imaging (fMRI) differences in brain activity of patients with schizophrenia. We searched PubMed and Scopus to find fMRI studies that assessed sex-based differences in the brain activity of patients with schizophrenia. We excluded studies that did not evaluate brain activity using fMRI, did not evaluate sex differences, and were nonhuman or in vitro studies. We found 12 studies that met the inclusion criteria for the current systematic review. Compared to females with schizophrenia, males with schizophrenia showed more blood oxygen level-dependent (BOLD) activation in the cerebellum, the temporal gyrus, and the right precuneus cortex. Male patients also had greater occurrence of low-frequency fluctuations in cerebral blood flow in frontal and parietal lobes and the insular cortex, while female patients had greater occurrence of low-frequency fluctuations in the hippocampus, parahippocampus, and lentiform nucleus. The current study summarizes fMRI studies that evaluated sex-based fMRI brain differences in schizophrenia that may help to shed light on the underlying pathophysiology and further understanding of sex-based differences in the clinical presentation and course of the disorder., (© 2024 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Background and Purpose: Understanding sex differences in typical development of the face processing network is important for elucidating disruptions during atypical development in sex-linked developmental disorders like autism spectrum disorder. Based on prior sex difference studies in other cognitive domains, this study examined whether females show increased integration of core and extended face regions with age for face viewing, while males would show increased segregation., Methods: This study used a cross-sectional design with typically developing children and adults (n = 133) and a functional MRI face localizer task. Psychophysiological interaction (PPI) analysis examined functional connectivity between canonical and extended face processing network regions with age, with greater segregation indexed by decreased core-extended region connectivity with age and greater integration indexed by increased core-extended region connectivity with age., Results: PPI analysis confirmed increased segregation for males-right fusiform face area (FFA) coupling to right inferior frontal gyrus (IFG) opercular when viewing faces and left amygdala when viewing objects decreased with age. Females showed increased integration with age (increased coupling of the right FFA to right IFG opercular region and right occipital face area [OFA] to right IFG orbital when viewing faces and objects, respectively) and increased segregation (decreased coupling with age of the right OFA with IFG opercular region when viewing faces)., Conclusions: Development of core and extended face processing network connectivity follows sexually dimorphic paths. These differential changes mostly occur across childhood and adolescence, with males experiencing segregation and females both segregation and integration changes in connectivity., (© 2023 American Society of Neuroimaging.)