ICD-11 presents updated descriptions for single episode and recurrent depressive disorder. A depressive episode (DE) is integral to these disorders and contrasting descriptions of the structure of DE symptoms are presented in ICD-11 and the Clinical Descriptions and Diagnostic Requirements for ICD-11 (CDDR). The former presents symptoms as unidimensional while the latter suggests symptoms are multidimensional reflecting affective, cognitive-behavioural, and vegetative clusters. This study examined if the latent structure of the DE symptoms is better represented by a one- or three-factor model. Data were collected from general population samples from the United Kingdom (UK: N=975) and Ukraine (N=2050). DE symptoms were measured using the International Depression Questionnaire, and the latent structure of the DE symptoms was assessed using confirmatory factor analysis. The three-factor model of DE symptoms outlined in the CDDR performed substantially better than the one-factor model and was a close fit to the UK and Ukrainian data. This model was invariant for sex in each nation. Prevalence estimates based on a three-factor model were similar to those based on the ICD-11 requirements, and similarly sized sex differences were observed. The multidimensional description of the DE symptoms outlined in the CDDR better represented data from two culturally distinct samples. Discrepancies in how DE symptoms are described in ICD-11 and the CDDR should be resolved to facilitate future research efforts.

Objective: This study examined sex differences in pain intensity and unpleasantness among cognitively healthy older adults. While females generally exhibit heightened pain sensitivity, research on sex differences in older adults remains limited. We aimed to determine whether these differences persist in aging populations without cognitive impairment. Methods: A sample of 58 community-dwelling older adults (≥60years, 34 females, 24 males) were included in this pain psychophysics study to assess differences by sex. Cognitive status was assessed using the Mini-Mental Status Exam (MMSE) or Telephone Interview for Cognitive Status (TICS). Depression, anxiety, and baseline pain were also assessed. Evoked heat pain stimuli at fixed temperatures (34°C, 39°C, 44°C) were delivered via the Medoc Q-Sense system with pain intensity and unpleasantness rated immediately after each stimulus. Results: Females reported significantly higher pain intensity than males (p = .02; female mean = 4.6 [95% CI: 3.9, 5.3], male mean = 3.5 [95% CI: 2.9, 4.2]). Sex differences in reported pain intensity were consistent across the three stimulus intensity levels (sex by temperature interaction p = .35). Pain unpleasantness did not differ significantly between sexes (p = .14) nor was the sex by temperature interaction significant (p = .35). Conclusion: Findings confirm sex differences in perceived pain intensity among cognitively healthy older adults, with females reporting higher pain levels. In contrast, no significant sex differences were observed in the affective component of pain. These results underscore the importance of incorporating sex-specific considerations in the assessment and management of pain intensity in older adults.

Sex differences in sit-and-reach flexibility in children and adolescents: A meta-analysis.

Sex differences in cancer incidence and survival have been documented, but underlying mechanisms remain unclear. We examined sex differences in incidence and survival for non-sex-specific cancers and the role of socioeconomic factors and comorbidity. All individuals living in Denmark from 2004-2020 were included. Incidence rate ratios (IRRs) and excess mortality ratios (EMRs) for 35 cancers were estimated using Poisson regression adjusted for age and year. Modification of associations between sex and death by cohabitation, education and comorbidity was assessed. A total of 7,339,667 individuals were followed for 99,832,998 person-years, during which 355,339 were registered with a primary malignancy (197,375 males, 157,964 females). Males had a 52% higher risk of cancer and upon cancer diagnosis 10% higher mortality than females. IRRs were elevated (with confidence intervals excluding the null) for 24 cancers and EMRs for 16 cancers in males. One in six cancers and one in five cancer deaths in males could have been avoided if male rates matched female rates. Disparities were greatest among males living alone, particularly for alcohol- and smoking-related cancers. Sex differences in cancer must be addressed and translated into interventions that promote equality between sexes, specifically focusing on socioeconomically vulnerable males.

Sex differences in calcific aortic valve disease (CAVD) progressing to aortic valve stenosis have been documented clinically, but the underlying cellular mechanisms that drive sex-dependent fibrocalcification in aortic valve tissue remain poorly understood. Human aortic valve tissues were analyzed via histological techniques and scanning electron microscopy to visualize and quantify sites of calcification. Single-cell and spatial transcriptomics were used to investigate mechanisms that drive sex-dependent spatial organization of valvular interstitial cell (VIC) and macrophage gene expression near calcification sites in human male and female aortic valve tissues. RNA in situ hybridization was used to validate sex-dependent gene expression near sites of calcification, and cell communication analyses were performed using bioinformatics tools to determine sex-dependent pathological cell-cell interactions. Histological analyses of aortic valve tissues from healthy patients and patients with CAVD reveal increased valve calcification area in CAVD male aortic valves relative to female valves. Single-cell sequencing analysis of heterogeneous VIC populations reveals male-biased gene expression of the AP-1 (activator protein 1) transcription factor complex and female-biased ECM (extracellular matrix) remodeling genes. Spatial transcriptomics analyses of VIC populations near histologically defined calcification sites revealed male-dependent localization of COMP or cartilage oligomeric matrix protein, as opposed to nonlocalized COMP expression in female VICs. Female CAVD tissues with increased fibrotic density had elevated expression of SERPINE1, encoding PAI-1 (plasminogen activator inhibitor-1), relative to male tissues. Female CAVD tissues also exhibited increased macrophage count heterogeneity relative to male tissues. Candidate ligand-receptor interactions, including osteopontin (SPP1) interacting with CD44, which encodes a cell-surface glycoprotein, were identified as contributors to inflammation-mediated CAVD. Our results reveal sex differences in VIC and macrophage heterogeneity and functions near sites of calcification in aortic valve tissue. Our results highlight the importance of sex-based transcriptomics analyses to understand the cellular phenotypes responsible for causing sex differences in aortic valve fibrocalcification.

Transcranial magnetic stimulation (TMS) is a promising intervention for alcohol use disorder (AUD), yet its efficacy varies widely. Scalp-to-cortex (STC) distance influences the strength of the induced electric field, and preliminary evidence suggests sex-specific craniofacial anatomy may contribute to STC variability. However, the implications of anatomical sex differences for TMS dosing in AUD remain unclear. This study examined whether STC distance and modeled electric field magnitude differ by sex, age, and alcohol use severity across common TMS targets. High-resolution structural magnetic resonance imaging was acquired from 107 individuals with AUD (59 females, 48 males). Individualized finite-element head models were generated using SimNIBS to calculate STC distance and electric field strength at four cortical targets: medial prefrontal cortex (Afz), dorsolateral prefrontal cortex (F3), ventromedial prefrontal cortex (Fp1), and motor cortex (C3). Linear mixed-effects models assessed the effects of sex, age, and Alcohol Use Disorders Identification Test (AUDIT) score. STC distance differed significantly across sites and was larger in males than in females, with sex differences strongest at Fp1 and C3. No sex differences were observed at Afz or F3. Higher AUDIT scores predicted greater STC distance independent of age. Electric field magnitude varied significantly across sites, with reduced values at midline regions (Afz, Fp1) relative to lateral sites (F3, C3). Electric field magnitude did not differ by sex overall. Age was associated with lower estimated electric field magnitude at the cortical surface. Exploratory sex-stratified analyses indicated a steeper age-related decline in females, particularly at medial prefrontal targets. Sex-specific and age-related anatomical differences influence cortical depth and effective stimulation strength in individuals with AUD. These findings highlight the need for individualized and potentially sex-tailored TMS dosing strategies, particularly for midline prefrontal targets and for older females who may be more vulnerable to reduced TMS engagement.

Alcohol use disorder (AUD) shows sex-related differences in prevalence, harm and treatment response. Despite growing interest in sex differences, evidence synthesis evaluating pharmacotherapy effectiveness by sex remains limited. Web of Science, PubMed, Scopus, PsycINFO and Cochrane were searched twice. Eligible records included RCTs or non-randomised studies of adults with AUD receiving pharmacological interventions (licensed or off-label), and reporting or providing outcomes (binary relapse or continuous alcohol consumption change) by sex. Multi-level random-effects models calculated risk ratios (RR) and standardised mean differences (SMD), with sex as a moderator. Twenty-eight studies (25,041 participants, 25% female) were included. No outcomes were rated low risk of bias; non-RCTs were moderate-to-high quality. Overall treatment effects vs. control were small for abstinence (RR = 0.96, 95% CI [0.52, 1.74]; 4 studies; I2 = 95%) and modest for consumption reduction (SMD = 0.23, 95% CI [0.01, 0.45]; 13 studies; I2 = 89%); sex did not meaningfully moderate these outcomes (ratio of RR = 1.04, 95% CI [0.87, 1.25]; ΔSMD = 0.05, 95% CI [-0.09, 0.18]). Power was low (median 13.7%), requiring ~6358 participants per group to detect the observed sex difference. Narrative synthesis suggested possible sex differences for naltrexone and baclofen, while highlighting the influence of drug (e.g., tolerability), participant (e.g., drinking motives) and design factors (e.g., recruitment setting) on treatment response. AUD pharmacotherapies provide modest benefits, with sex differences remaining unclear. Future trials should be adequately powered, report sex-specific outcomes and consider adherence, tolerability and psychosocial moderators. Evidence for sex-specific efficacy remains inconclusive. Patterns for naltrexone and baclofen warrant exploration in large, rigorously designed, sex-stratified trials.

Sex differences in resting-state EEG microstates and working memory in first-episode, medication-naïve major depressive disorder.

Osteometric characterization of distal limb elements in domestic yak (Bos grunniens): Morphological adaptations and sexual dimorphism.

Caudal pseudoautotomy, defined as intervertebral tail breakage without regeneration, has been reported in several snake taxa; however, its frequency and association with biological factors remain poorly documented in some arboreal species. We investigated the occurrence of caudal pseudoautotomy in the Neotropical colubrid Leptophis marginatus based on 151 museum specimens. We assessed sexual dimorphism using adult individuals with intact tails and tested for differences in the frequency of pseudoautotomy between males and females. Caudal pseudoautotomy affected 58 (38.4%) of the 151 L. marginatus specimens. We did not detect significant differences in pseudoautotomy frequency between males and females. We detected sexual dimorphism in snout-vent length and tail length in L. marginatus, with males attaining larger body and tail sizes. These results provide the first quantitative assessment of caudal pseudoautotomy in L. marginatus and suggest that tail breakage is a common defensive trait in this species. Keywords: tail breakage, antipredator behaviour, museum specimens, sexual dimorphism, arboreal snake

Uncertainty-aware type-II fuzzy graph modeling of resting-state fMRI uncovers robust sex differences.

Potentially traumatic events (PTEs) are associated with cardiovascular disease (CVD) in aging populations. Despite sex differences in PTE exposure and CVD incidence, no study has examined sex-specific associations between PTEs and CVD in the same sample of middle-aged and older adults. Using data from the Health and Retirement Study, we examined lifetime exposure to 18 PTEs across three domains: early life adversity, lifetime trauma, and perceived discrimination and CVD (stroke or heart disease). We used Cox proportional hazards regression to calculate crude and adjusted (race/ethnicity, age, and educational attainment) hazard ratios (aHRs) and 95% confidence intervals (CI). Among 12,272 HRS participants, nearly 80% reported experiencing at least one PTE. Within domains, child abuse and serious accident or illness had the strongest associations with CVD for men, aHR=1.26, 95% CI [1.04, 1.52], aHR=1.68, 95% CI [1.53, 1.85], respectively, and women, aHR=1.35, 95% CI [1.17, 1.56], aHR=1.80, 95% CI [1.64, 1.97], respectively. Sex differences were noted for perceived discrimination-for men, the strongest association was between being prevented from moving into other housing and CVD, aHR=1.52, 95% CI [1.08, 2.14], and for women, the strongest association was between being denied health care and CVD, aHR=1.43, 95% CI [1.08, 1.90]. For both sexes, experiencing a higher number of PTEs was associated with an increased rate of CVD. Differences among men and women in these results offer insight into opportunities for prevention and targeted clinical interventions in this age group.

There are age and sex differences in the processing of social reward, although the basis for these differences is not well established. We previously found greater social motivation at P50 (postpubertal adolescence) than at P70 (adulthood), and that female rats showed greater social motivation than male rats. Thus, we investigated whether gonadal hormones may contribute to age and sex differences in social reward motivation. Rats underwent either gonadectomy or sham surgery at P41 (adolescent group) or P69 (adult group) and began testing in the operant conditioning paradigm 5days later. When trained on a fixed ratio of one, gonadectomized rats had a greater social preference relative to control rats, irrespective of sex and age. When tested on a progressive ratio (effort required to access social reward continually increased), adolescents were more motivated than were adults, irrespective of sex or gonadal status. However, resistance to extinction was evident in gonadectomized rats relative to control rats, irrespective of sex and age. Thus, the results provide evidence that gonadal hormones influence social preference, although not social motivation. Ongoing maturation, rather than puberty, is responsible for age-related changes in social reward motivation, and the presence of gonadal hormones independently influences the preference for a social partner.

Sex-specific brain morphometric associations with psychopathology severity in obsessive-compulsive disorder.

Congenital heart disease in a singleton pregnancy conceived through assisted reproductive technology.

Alcohol consumption is strongly associated with aggression and violence in humans, yet the underlying neurobiological mechanisms within key aggression circuits remain poorly understood. In this preclinical study, we examined the effects of intermittent alcohol intoxication on dominance and aggressive behaviors in mice, focusing on sex differences and the potential involvement of the nucleus incertus relaxin-3/relaxin-family peptide receptor 3 (RXFP3) signaling pathway. Using an intermittent ethanol-intoxication protocol, we observed that male mice displayed a transient increase in dominance and aggressive behaviors during acute abstinence, as measured by the tube-dominance and resident-intruder tests, whereas female mice displayed heightened defensive responses. Distinct patterns of neural activation across brain regions, reflected by c-Fos protein expression, were associated with aggression in males, including decreased expression in the medial amygdala (MeA) and increased expression in the ventromedial hypothalamus (VMH), consistent with an established MeA-VMH based aggression circuit. Additionally, the levels of relaxin-3 immunoreactivity in MeA nerve fibers increased in parallel with behavioral recovery, suggesting a modulatory role of relaxin-3/RXFP3 signaling. To test this hypothesis, we bilaterally injected an adeno-associated viral (AAV) vector expressing the selective RXFP3 agonist, R3/I5, into the MeA of male mice. Notably, this chronic localized R3/I5 treatment significantly reduced dominance and aggressive behaviors both before and after alcohol intoxication. Together, these data demonstrate that relaxin-3/RXFP3 signaling in the MeA counteracts alcohol-related aggression in male mice, pointing to this pathway as a potential target for treating impulsive violence associated with alcohol intoxication in humans.

Echolocating animals actively emit pulses of ultrasound and perceive acoustic reflections to determine the position of objects in dark, often three-dimensional spaces. Echolocation specificity thus depends on the properties of the calls emitted, such as frequency, duration, and call "shape", and how this ultrasound is modulated, reflected, received, and interpreted. Currently, however, there is no coherent synthesis explaining the functional adaptation of ultrasonic call design across echolocating species. To address this, here we provide the first comprehensive global macroevolutionary analysis of echolocator call design in relation to functional adaptations. From a systematic literature review, we identified 1,329 echolocating mammal and bird species, with a predominantly pan-tropical distribution, plus an additional 117 unconfirmed echolocators. To link echolocation call design to functional adaptations, we characterized calls based on 5,146 acoustic records from 2,838 terrestrial and aquatic study sites across 140 countries. From a comparative phylogenetic analysis, we established that echolocation calls were linked to (i) call frequency- and variation related parameters, which were associated with orientation function, and (ii) call type and duration, which mediated prey acquisition. Although echolocators produced highly species-specific calls, we found no support for any consistent effect of social system or sexual size dimorphism on echolocation call characteristics; however, morphological and phylogenetic constraints did substantially influence echolocation call designs at the global scale. This link between echolocation call design and function underscores how calls are adapted to overarching ecological niche conditions, explaining the conceptual macroevolutionary basis for the global distribution and adaptive radiation of echolocating species.

Mercury bioaccumulation patterns and toxicological risk across tissues in the Black-browed albatross (Thalassarche melanophris) from the Southwestern Atlantic.

Tirzepatide, an injectable glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist (RA), is approved for weight management in several regions. Oral GLP-1 RAs, such as semaglutide, are under investigation to improve convenience, acceptance and adherence versus injectable formulations. Currently, no studies have compared the efficacy and safety of tirzepatide with oral semaglutide for weight management. This study aimed to indirectly compare the efficacy and safety of weekly injectable tirzepatide 5, 10 and 15 mg for weight management in obesity and overweight versus daily oral semaglutide 50 mg. Pivotal trials SURMOUNT-1 (tirzepatide, Week 72) and OASIS 1 (oral semaglutide, Week 68) were compared using multilevel network meta-regression (ML-NMR) to adjust for differences in sex, ethnicity and outcome baselines between trial populations. Participants were adults without type 2 diabetes and with obesity (BMI ≥ 30 kg/m2), or overweight (BMI ≥ 27 kg/m2) with ≥ 1 obesity-related complication. Tirzepatide 10 and 15 mg were associated with statistically significantly greater reductions in weight (mean difference: -4.48% [-6.35, -2.61] and -5.59% [-7.52, -3.77]) and waist circumference (-3.60 cm [-5.59, -1.72] and -4.32 cm [-6.30, -2.40]), and higher odds of achieving ≥ 5%/10%/15%/20% weight reduction compared with oral semaglutide. Cardiometabolic benefits and safety profiles were improved or generally comparable for tirzepatide versus oral semaglutide. This ML-NMR provides an indirect comparison of injectable tirzepatide with oral semaglutide for weight management. Tirzepatide was associated with statistically significantly greater weight and waist circumference reduction versus oral semaglutide and improved or similar cardiometabolic benefits and safety.

Homothorax regulates BarH1 expression and olfactory perception in Monochamus alternatus hope.