Male Samples Research Articles

Abstract 3764: Spatially resolved immune landscape revealed sex-biased T-cell infiltration in glioblastoma

Abstract Glioblastoma (GBM) multiforme is the most aggressive type of brain cancer. These lethal brain tumors are characterized by the inter- and intra-tumor molecular heterogeneity and demonstrated cell plasticity. A male:female distribution of 1.6:1; survival outcome from treatment (debulking, radiation, and temozolomide) benefits females nearly twice that for males. Through spatial transcriptomics, we interrogated the immune landscape of GBM, seeking to tease out whether distinct biological and therapeutic niches in GBM were evident, and to understand how the tumor microenvironments contributed to the heterogeneity of GBM. We designed a set of RNA hybridization probes specifically for portraying the cell identities and cell functional states within GBM tumor. The probe set was used to profile six human GBM samples from male and female cohorts on the Vizgen MERSCOPE platform. An integrated analysis of 505,614 cells from the six samples yielded a rich and varied spatial cell atlas of glioblastoma. Our preliminary findings depict distinct spatial niches of different tumor cell subpopulations that are associated with local environmental factors such as hypoxia. We identified a small cluster of cells that are in neuronal-like state, which could potentially drive invasion. We found spatial proximity of CD4+ cells and cells that express HIF1A, suggesting the dynamic interactions between tumor cells, regulatory T cells and tumor microenvironment. We also observed significant difference in the degree of CD8+ T-cell infiltration in female samples versus male samples. The average CD4+/CD8+ T-cell ratio in males is twice as high as that of females, suggesting intrinsic sex-based differences in immune response to tumor. Expansion of these studies in additional specimens will further illuminate microenvironmental influences on glioma progression and may instruct specific interventions leading to more effective and predictable immune-oncology of this disease. Citation Format: Yue Hao, George Reid, Angela Baker, Karen L. Fink, George J. Snipes, Bruce E. Mickey, Andrew E. Sloan, Jill S. Barnholtz-Sloan, Michael Berens. Spatially resolved immune landscape revealed sex-biased T-cell infiltration in glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3764.

A sex-specific pathway linking early life maltreatment, vagal activity, and depressive symptoms

ABSTRACT Background: Experiences of early life maltreatment (ELM) are alarmingly common and represent a risk factor for the development of psychopathology, particularly depression. Research has focused on alterations in autonomic nervous system (ANS) functioning as a mediator of negative mental health outcomes associated with ELM. Early alterations in autonomic vagal activity (vmHRV) may moderate the relationship between ELM and depression, particularly when considering forms of emotional maltreatment. Recent evidence suggests that the relationships of both ELM and vmHRV with depression may be non-linear, particularly considering females. Objective: Building on and extending theoretical considerations and previous work, the present work aims to further the current understanding of the complex relationships between ELM exposure, vmHRV, and depression. Methods: This study uses an adaptive modelling approach, combining exploratory network-based analyses with linear and quadratic moderation analyses, drawing on a large sample of males and females across adolescence (total N = 213; outpatient at-risk sample and healthy controls) and adulthood (total N = 85; community-based convenience sample). Results: Exploratory network-based analyses reveal that exposure to emotional abuse is particularly central within a network of ELM subtypes, depressive symptoms, and concurrent vmHRV in both adolescents and adults. In adults, emotional neglect shows strong associations with both emotional abuse and vmHRV and is highly central as a network node, which is not observed in adolescents. Moderator analyses reveal significant interactions between emotional maltreatment and vmHRV predicting depressive symptoms in adult females. Significant quadratic relationships of emotional maltreatment and vmHRV with depression are observed in both adolescent and adult females. Conclusions: The present findings contribute to the understanding of the psychological and physiological mechanisms by which ELM acts as a risk factor for the development of depression. Ultimately, this will contribute to the development of targeted and effective intervention strategies to mitigate the detrimental effects of early adversity.

Meta Data Analysis of Sex Distribution of Study Samples Reported in Summer Biomechanics, Bioengineering, and Biotransport Annual Conference Abstracts.

The biased use of male subjects in biomedical research has created limitations, underscoring the importance of including women to enhance the outcomes of evidence-based medicine and to promote human health. While federal policies (e.g., the 1993 Revitalization Act and the 2016 Sex as a Biological Variable Act) have aimed to improve sex balance in studies funded by the National Institutes of Health (NIH), data on sex inclusivity in non-NIH funded research remain limited. The objective of this study was to analyze the trend of sex inclusion in abstracts submitted to the Summer Biomechanics, Bioengineering, & Biotransport Conference (SB3C) over 7 years. We scored every abstract accepted to SB3C, and the findings revealed that approximately 20% of total abstracts included sex-related information, and this trend remained stable. Surprisingly, there was no significant increase in abstracts, including both sexes and those with balanced female and male samples. The proportion of abstracts with balanced sexes was notably lower than those including both sexes. Additionally, we examined whether the exclusion of one sex from the corresponding studies was justified by the research questions. Female-only studies had a 50% justification rate, while male-only studies had only 2% justification. Disparity in sex inclusion in SB3C abstracts was apparent, prompting us to encourage scientists to be more mindful of the sex of the research samples. Addressing sex inclusivity in biomechanics and mechanobiology research is essential for advancing medical knowledge and for promoting better healthcare outcomes for everyone.

Indonesian Happiness Factor: A Panel Data Analysis

The measurement of welfare level is one of the success benchmarks of a country's developmental program. Welfare assessments in the form of subjective well-being (SWB) can complement the objective measures. In assessing SWB, economists use happiness and life satisfaction questions. Therefore, this study aims to analyze the factors that influence individual happiness in Indonesia. The panel data from the last two waves of the Indonesia Family Life Survey (IFLS), namely IFLS 4 (2007) and IFLS 5 (2014) were used. The analytical tool was panel data regression with a fixed effect approach. The results showed religiosity, generalized trust, altruism, and education-age interaction significantly affected happiness levels. This study implies the higher the year of education, the more positive the effect of age on happiness level. Furthermore, the control variables, namely marital status, subjective health, perceived safety, and per capita expenditure are significant, while unemployment affected the happiness level of only the male sample. The government and public figures in Indonesia may promote initiatives that facilitate religiosity, trust, and altruism development, for instance, promoting activities that require involvement from different stakeholders in the community. They also should become role models showing altruism and religiosity.

Prison Buprenorphine Implementation and Postrelease Opioid Use Disorder Outcomes

Agonist medications for opioid use disorder (MOUD), buprenorphine and methadone, in carceral settings might reduce the risk of postrelease opioid overdose but are uncommonly offered. In April 2019, the Massachusetts Department of Correction (MADOC), the state prison system, provided buprenorphine for incarcerated individuals in addition to previously offered injectable naltrexone. To evaluate postrelease outcomes after buprenorphine implementation. This cohort study with interrupted time-series analysis used linked data across multiple statewide data sets in the Massachusetts Public Health Data Warehouse stratified by sex due to differences in carceral systems. Eligible participants were individuals sentenced and released from a MADOC facility to the community. The study period for the male sample was January 2014 to November 2020; for the female sample, January 2015 to October 2019. Data were analyzed between February 2022 and January 2024. April 2019 implementation of buprenorphine during incarceration. Receipt of MOUD within 4 weeks after release, opioid overdose, and all-cause mortality within 8 weeks after release, each measured as a percentage of monthly releases who experienced the outcome. Segmented linear regression analyzed changes in outcome rates after implementation. A total of 15 225 individuals were included. In the male sample there were 14 582 releases among 12 688 individuals (mean [SD] age, 35.0 [10.8] years; 133 Asian and Pacific Islander [0.9%], 4079 Black [28.0%], 4208 Hispanic [28.9%], 6117 White [41.9%]), a rate of 175.7 releases per month; the female sample included 3269 releases among 2537 individuals (mean [SD] age, 34.9 [9.8] years; 328 Black [10.0%], 225 Hispanic [6.9%], 2545 White [77.9%]), a rate of 56.4 releases per month. Among male participants at 20 months postimplementation, the monthly rate of postrelease buprenorphine receipt was higher than would have been expected under baseline trends (21.2% vs 10.6% of monthly releases; 18.6 additional releases per month). Naltrexone receipt was lower than expected (1.0% vs 6.0%; 8.8 fewer releases per month). Monthly rates of methadone receipt (1.4%) and opioid overdose (1.8%) were not significantly different than expected. All-cause mortality was lower than expected (1.9% vs 2.8%; 1.5 fewer deaths per month). Among female participants at 7 months postimplementation, buprenorphine receipt was higher than expected (31.6% vs 9.5%; 12.4 additional releases per month). Naltrexone receipt was lower than expected (3.4% vs 7.2%) but not statistically significantly different. Monthly rates of methadone receipt (1.1%), opioid overdose (4.8%), and all-cause mortality (1.6%) were not significantly different than expected. In this cohort study of state prison releases, postrelease buprenorphine receipt increased and naltrexone receipt decreased after buprenorphine became available during incarceration.

Cannabis Dependence is Associated with Reduced Hippocampal Subregion Volumes Independently of Sex: Findings from an ENIGMA Addiction Working Group Multi-Country Study.

Background: Males and females who consume cannabis can experience different mental health and cognitive problems. Neuroscientific theories of addiction postulate that dependence is underscored by neuroadaptations, but do not account for the contribution of distinct sexes. Further, there is little evidence for sex differences in the neurobiology of cannabis dependence as most neuroimaging studies have been conducted in largely male samples in which cannabis dependence, as opposed to use, is often not ascertained. Methods: We examined subregional hippocampus and amygdala volumetry in a sample of 206 people recruited from the ENIGMA Addiction Working Group. They included 59 people with cannabis dependence (17 females), 49 cannabis users without cannabis dependence (20 females), and 98 controls (33 females). Results: We found no group-by-sex effect on subregional volumetry. The left hippocampal cornu ammonis subfield 1 (CA1) volumes were lower in dependent cannabis users compared with non-dependent cannabis users (p<0.001, d=0.32) and with controls (p=0.022, d=0.18). Further, the left cornu ammonis subfield 3 (CA3) and left dentate gyrus volumes were lower in dependent versus non-dependent cannabis users but not versus controls (p=0.002, d=0.37, and p=0.002, d=0.31, respectively). All models controlled for age, intelligence quotient (IQ), alcohol and tobacco use, and intracranial volume. Amygdala volumetry was not affected by group or group-by-sex, but was smaller in females than males. Conclusions: Our findings suggest that the relationship between cannabis dependence and subregional volumetry was not moderated by sex. Specifically, dependent (rather than non-dependent) cannabis use may be associated with alterations in selected hippocampus subfields high in cannabinoid type 1 (CB1) receptors and implicated in addictive behavior. As these data are cross-sectional, it is plausible that differences predate cannabis dependence onset and contribute to the initiation of cannabis dependence. Longitudinal neuroimaging work is required to examine the time-course of the onset of subregional hippocampal alterations in cannabis dependence, and their progression as cannabis dependence exacerbates or recovers over time.

Whole-Exome Sequencing (WES) Reveals Novel Sex-Specific Gene Variants in Non-Alcoholic Steatohepatitis (MASH).

Non-alcoholic steatohepatitis (NASH, also known as MASH) is a severe form of non-alcoholic fatty liver disease (NAFLD, also known as MASLD). Emerging data indicate that the progression of the disease to MASH is higher in postmenopausal women and that genetic susceptibility increases the risk of MASH-related cirrhosis. This study aimed to investigate the association between genetic polymorphisms in MASH and sexual dimorphism. We applied whole-exome sequencing (WES) to identify gene variants in 8 age-adjusted matched pairs of livers from both male and female patients. Sequencing alignment, variant calling, and annotation were performed using standard methods. Polymerase chain reaction (PCR) coupled with Sanger sequencing and immunoblot analysis were used to validate specific gene variants. cBioPortal and Gene Set Enrichment Analysis (GSEA) were used for actionable target analysis. We identified 148,881 gene variants, representing 57,121 and 50,150 variants in the female and male cohorts, respectively, of which 251 were highly significant and MASH sex-specific (p < 0.0286). Polymorphisms in CAPN14, SLC37A3, BAZ1A, SRP54, MYH11, ABCC1, and RNFT1 were highly expressed in male liver samples. In female samples, Polymorphisms in RGSL1, SLC17A2, HFE, NLRC5, ACTN4, SBF1, and ALPK2 were identified. A heterozygous variant 1151G>T located on 18q21.32 for ALPK2 (rs3809983) was validated by Sanger sequencing and expressed only in female samples. Immunoblot analysis confirmed that the protein level of β-catenin in female samples was 2-fold higher than normal, whereas ALPK2 expression was 0.5-fold lower than normal. No changes in the protein levels of either ALPK2 or β-catenin were observed in male samples. Our study suggests that the perturbation of canonical Wnt/β-catenin signaling observed in postmenopausal women with MASH could be the result of polymorphisms in ALPK2.

Parental kinship coefficient but not paternal coloration predicts early offspring growth in lake char

The ‘good genes’ hypotheses of sexual selection predict that females prefer males with strong ornaments because they are in good health and vigor and can afford the costs of the ornaments. A key assumption of this concept is that male health and vigor are useful predictors of genetic quality and hence offspring performance. We tested this prediction in wild-caught lake char (Salvelinus umbla) whose breeding coloration is known to reveal aspects of male health. We first reanalyzed results from sperm competition trials in which embryos of known parenthood had been raised singly in either a stress- or non-stress environment. Paternal coloration did not correlate with any measures of offspring performance. However, offspring growth was reduced with higher kinship coefficients between the parents. To test the robustness of these first observations, we collected a new sample of wild males and females, used their gametes in a full-factorial in vitro breeding experiment, and singly raised about 3000 embryos in either a stress- or non-stress environment (stress induced by microbes). Again, paternal coloration did not predict offspring performance, while offspring growth was reduced with higher kinship between the parents. We conclude that, in lake char, the genetic benefits of mate choice would be strongest if females could recognize and avoid genetically related males, while male breeding colors may be more relevant in intra-sexual selection.

Gender-specific genetic and epigenetic signatures in cardiovascular disease.

Cardiac sex differences represent a pertinent focus in pursuit of the long-awaited goal of personalized medicine. Despite evident disparities in the onset and progression of cardiac pathology between sexes, historical oversight has led to the neglect of gender-specific considerations in the treatment of patients. This oversight is attributed to a predominant focus on male samples and a lack of sex-based segregation in patient studies. Recognizing these sex differences is not only relevant to the treatment of cisgender individuals; it also holds paramount importance in addressing the healthcare needs of transgender patients, a demographic that is increasingly prominent in contemporary society. In response to these challenges, various agencies, including the National Institutes of Health, have actively directed their efforts toward advancing our comprehension of this phenomenon. Epigenetics has proven to play a crucial role in understanding sex differences in both healthy and disease states within the heart. This review presents a comprehensive overview of the physiological distinctions between males and females during the development of various cardiac pathologies, specifically focusing on unraveling the genetic and epigenetic mechanisms at play. Current findings related to distinct sex-chromosome compositions, the emergence of gender-biased genetic variations, and variations in hormonal profiles between sexes are highlighted. Additionally, the roles of DNA methylation, histone marks, and chromatin structure in mediating pathological sex differences are explored. To inspire further investigation into this crucial subject, we have conducted global analyses of various epigenetic features, leveraging data previously generated by the ENCODE project.

Awareness of lung cancer risk factors and symptoms in Syria: an online cross-sectional study

Background Globally, lung cancer is the leading cause of cancer fatalities and the second most frequent cancer. Population knowledge of the features of lung cancer is a crucial strategy for early diagnosis and decreasing the mortality rate of lung cancer patients. In this study, we aim to assess the Syrian population’s knowledge of lung cancer and its risk factors and to measure awareness of symptoms related to lung cancer. Methods This national cross-sectional study was conducted between October 12 to November 21, 2022, in Syria. We included Syrian people above 18 years from all Syrian governorates. The questionnaire consisted of three categories of questions: sociodemographic information, awareness of lung cancer symptoms, and awareness of lung cancer risk factors. Results Overall, 2251 participants were involved in this research; almost half of them (47.3%) were aged between 21-30 years, and 30.9% indicated they are smoking cigarettes. The overall mean score of knowledge regarding closed questions about risk factors of lung cancer was 4.29; however, the mean score of knowledge regarding open questions about symptoms of lung cancer was 1.52. About half of the study sample (51.3%) indicated that unexplained weight loss is a possible symptom of lung cancer. Our findings showed that cigarette smokers have a lower probability of having adequate knowledge toward lung cancer risk factors than a non-smoker (AOR=0.73, COR=0.68, P-value&lt;0.05). We also defined that females have higher statistically significant odds (AOR=1.3, COR=1.38, P-value&lt;0.05) for being knowledgeable about the symptoms of lung cancer compared to the male sample study. Conclusion According to our findings, there is inadequate knowledge toward lung cancer risk factors and moderate knowledge of lung cancer symptoms. Along with educational programs to raise public knowledge of the dangers of smoking and other LC risk factors, effective tobacco control policy execution is crucial.

Effects of Tcte1 knockout on energy chain transportation and spermatogenesis: implications for male infertility.

Is the Tcte1 mutation causative for male infertility? Our collected data underline the complex and devastating effect of the single-gene mutation on the testicular molecular network, leading to male reproductive failure. Recent data have revealed mutations in genes related to axonemal dynein arms as causative for morphology and motility abnormalities in spermatozoa of infertile males, including dysplasia of fibrous sheath (DFS) and multiple morphological abnormalities in the sperm flagella (MMAF). The nexin-dynein regulatory complex (N-DRC) coordinates the dynein arm activity and is built from the DRC1-DRC7 proteins. DRC5 (TCTE1), one of the N-DRC elements, has already been reported as a candidate for abnormal sperm flagella beating; however, only in a restricted manner with no clear explanation of respective observations. Using the CRISPR/Cas9 genome editing technique, a mouse Tcte1 gene knockout line was created on the basis of the C57Bl/6J strain. The mouse reproductive potential, semen characteristics, testicular gene expression levels, sperm ATP, and testis apoptosis level measurements were then assessed, followed by visualization of N-DRC proteins in sperm, and protein modeling in silico. Also, a pilot genomic sequencing study of samples from human infertile males (n = 248) was applied for screening of TCTE1 variants. To check the reproductive potential of KO mice, adult animals were crossed for delivery of three litters per caged pair, but for no longer than for 6 months, in various combinations of zygosity. All experiments were performed for wild-type (WT, control group), heterozygous Tcte1+/- and homozygous Tcte1-/- male mice. Gross anatomy was performed on testis and epididymis samples, followed by semen analysis. Sequencing of RNA (RNAseq; Illumina) was done for mice testis tissues. STRING interactions were checked for protein-protein interactions, based on changed expression levels of corresponding genes identified in the mouse testis RNAseq experiments. Immunofluorescence in situ staining was performed to detect the N-DRC complex proteins: Tcte1 (Drc5), Drc7, Fbxl13 (Drc6), and Eps8l1 (Drc3) in mouse spermatozoa. To determine the amount of ATP in spermatozoa, the luminescence level was measured. In addition, immunofluorescence in situ staining was performed to check the level of apoptosis via caspase 3 visualization on mouse testis samples. DNA from whole blood samples of infertile males (n = 137 with non-obstructive azoospermia or cryptozoospermia, n = 111 samples with a spectrum of oligoasthenoteratozoospermia, including n = 47 with asthenozoospermia) was extracted to perform genomic sequencing (WGS, WES, or Sanger). Protein prediction modeling of human-identified variants and the exon 3 structure deleted in the mouse knockout was also performed. No progeny at all was found for the homozygous males which were revealed to have oligoasthenoteratozoospermia, while heterozygous animals were fertile but manifested oligozoospermia, suggesting haploinsufficiency. RNA-sequencing of the testicular tissue showed the influence of Tcte1 mutations on the expression pattern of 21 genes responsible for mitochondrial ATP processing or linked with apoptosis or spermatogenesis. In Tcte1-/- males, the protein was revealed in only residual amounts in the sperm head nucleus and was not transported to the sperm flagella, as were other N-DRC components. Decreased ATP levels (2.4-fold lower) were found in the spermatozoa of homozygous mice, together with disturbed tail:midpiece ratios, leading to abnormal sperm tail beating. Casp3-positive signals (indicating apoptosis) were observed in spermatogonia only, at a similar level in all three mouse genotypes. Mutation screening of human infertile males revealed one novel and five ultra-rare heterogeneous variants (predicted as disease-causing) in 6.05% of the patients studied. Protein prediction modeling of identified variants revealed changes in the protein surface charge potential, leading to disruption in helix flexibility or its dynamics, thus suggesting disrupted interactions of TCTE1 with its binding partners located within the axoneme. All data generated or analyzed during this study are included in this published article and its supplementary information files. RNAseq data are available in the GEO database (https://www.ncbi.nlm.nih.gov/geo/) under the accession number GSE207805. The results described in the publication are based on whole-genome or exome sequencing data which includes sensitive information in the form of patient-specific germline variants. Information regarding such variants must not be shared publicly following European Union legislation, therefore access to raw data that support the findings of this study are available from the corresponding author upon reasonable request. In the study, the in vitro fertilization performance of sperm from homozygous male mice was not checked. This study contains novel and comprehensive data concerning the role of TCTE1 in male infertility. The TCTE1 gene is the next one that should be added to the 'male infertility list' because of its crucial role in spermatogenesis and proper sperm functioning. This work was supported by National Science Centre in Poland, grants no.: 2015/17/B/NZ2/01157 and 2020/37/B/NZ5/00549 (to M.K.), 2017/26/D/NZ5/00789 (to A.M.), and HD096723, GM127569-03, NIH SAP #4100085736 PA DoH (to A.N.Y.). The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Immediate Effect of Simulated High Heels on Pelvic and Spinal Posture in Healthy Young Subjects: A Cross-Sectional Study.

Background Investigations regarding the role of high-heeled shoes in the alteration of the spinopelvic profile attempted to identify a correlation with pain in the lower back. Conclusions from these studies, however, are controversial. In authors knowledge no studies were carried out to investigate the effect of heels on male population, which has been overlooked due to gender-related customs. Research question What is the immediate effect of the height of heels on the sagittal back profile (trunk inclination (TI), pelvic inclination, lordotic lumbar angle (ITL-ILS), kyphotic dorsal angle, lumbar arrow, and cervical arrow) in females and males, not used to wearing high-heeled shoes? Methods One hundred healthy young adult subjects were enrolled. Three were excluded. The remaining 97 subjects (48 female and 49 male) underwent a three-dimensional analysis of the posterior surface of the trunk, using rasterstereography. The spinopelvic profile in the barefoot condition, and with the heel raised by 3 and 7 cm, was recorded. To evaluate the reproducibility of the measure, the neutral evaluation was repeated twice in 23 subjects (13 males, 10 females). Results The change of heel height did not show statistically significant differences for any of the variables used; instead, significant differences were found stratifying the results according to the sex of the subjects tested. Test-retest evaluation in the neutral condition showed no significant differences using the Student's t-test (p > 0.05). Repeatability was excellent and significant for all data used (minimum TI r = 0.85, maximum ITL-ILS r = 0.97). Significance Studying the effect of heels on the spino-pelvic profile also in the male population is crucial for promoting gender-inclusive healthcare, enhancing occupational health practices and developing possible preventive measures. Nevertheless, in the sample of females and males evaluated in this study, the different heights of heel lift did not immediately induce significant changes in pelvis and spine posture. If there is therefore a correlation between low-back pain and the use of heels, it should not reasonably be sought in the immediate change of the spino-pelvic profile caused by raising the heels. However, the variables analyzed differed according to sex.

Abstract B039: Identification of sex-specific molecular features in glioma transcriptome

Abstract Glioma is a lethal disease with limited treatment options available. Sex differences in glioma are well-documented in clinical settings, with males having twice the risk of developing the disease and increased mortality compared to female counterparts. To investigate the molecular basis of sex differences in glioma, we analyzed transcriptomic sex differences in a collection of three independent glioma datasets and validated them in additional independent studies. The impact of differentially expressed genes were assessed through Gene Set Enrichment Analysis (GSEA) on approximately 5000 gene sets to interpret their biological relevance. Given the well-recognized heterogeneity of glioma, we also integrated three single-cell RNA (scRNA) sequencing datasets to decipher the sex differences in cellular composition and cell-type specific differential gene expression between male and female tumors. The effects of sex on gene expression are modest and primarily driven by the X chromosome (14 out of 16 differentially expressed genes were on the X chromosome). These genes are associated with escape from X-chromosome inactivation (e.g., KDM5C, KDM6A) and are also sex-differentially expressed (DE) in the healthy human brain according to Genotype-Tissue Expression (GTEx) data. GSEA results suggest increased activity in cell proliferation and neuronal signaling in male GBM samples, whereas females show enrichment in glycoprotein/lipid metabolism. By deconvoluting the cell-type composition, we identified a higher percentage of pericytes in the male glioma tumor microenvironment compared to those in females, which is consistent with recent spatial-omic discoveries in glioma. By integrating scRNA sequencing data, we found that both differentially expressed genes and pathways show cell-type-specific enrichment. For example, the female-biased gene GBGT1 is exclusively expressed in the myeloid lineage, while male-biased neuronal pathways are enriched in cancer stem cells. Integrating with the inference of cell trajectories, we observed that male tumors harbor more unconnected, invasive malignant cells than females, which might explain the poor prognosis in male glioma patients. In summary, our results provide a comprehensive multi-level characterization of sex differences in glioma tumors, and these findings will provide novel insights into glioma disease progression and development of new therapy. Citation Format: Yingbo Huang, Yuting Shan, Weijie Zhang, Christina Printzis, Lorenzo Pesce, Barbara Elaine Stranger, R. Stephanie Huang. Identification of sex-specific molecular features in glioma transcriptome [abstract]. In: Proceedings of the AACR Special Conference on Brain Cancer; 2023 Oct 19-22; Minneapolis, Minnesota. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_1):Abstract nr B039.

Patrilocality at the Beginning of Farming? An Isotopic Approach from SE Moravia

This research combines Strontium (87Sr/86Sr) and Oxygen (δ18O) isotope analysis to challenge the prevailing interpretation of patrilocal exogamic practices among eastern European Early Neolithic Linearbandkeramik (LBK) communities. Patrilocality has been considered the key factor influencing the mobility patterns of central Europe’s first farmers (c. 5500–4900 cal. BC), especially in the south-eastern Moravian region (Czech Republic). Focusing our attention on both male and female tooth enamel samples from cemeteries, settlement graves and small clusters of graves, this paper reassesses the correlation between mobility, biological sex, and funerary practices. This task is accomplished by establishing a new isotopic footprint using new 87Sr/86Sr data, as well as significantly increasing the number of sampled individuals for 87Sr/86Sr and δ18O. The outcome of this research contributes to a better understanding of the mobility patterns among early farmers in central Europe, challenging existing theories and providing new insights into their social and cultural dynamics.

Ketika kekerasan dianggap seksi: persepsi laki-laki bahwa perempuan suka kekerasan memicu pola pikir ekstremis militan

Inspired by the paradigm of mate selection motives in evolutionary psychology, this research seeks to determine the extent to which violent extremist thought patterns are a product of perceptions of attractiveness that persist in men as a response to intrasexual selection. The survey was conducted on 192 samples of the general population in Indonesia, on a male sample (n = 80), after controlling for demographic variables, including dark personality (dark triad), men's subjective perception that Indonesian women find violence attractive (PAOSV) predicts militant-extremist mindset. PAOSV was the only variable that predicted violent extremism mindset in men. Furthermore, we discovered a mechanism that we call “sexualization of violence” – namely the extent to which individuals perceive violence as sexy, manly, and cool (AV) as a process that arises from the perception of high levels of positive feedback from the opposite sex towards violence. Where in the sample of men in this study, the only variable that shaped the mindset of violent extremism was sexual motives. The discussion elaborate differences in perceptions of attraction to violence between men and women, differentiation and gaps in perceptions between men and women in assessing violence. This study has practical implications, namely discussing the importance of the role of women as active agents in the formation of a culture of nonviolence.

Comprehensive Sex-Stratified Genetic Analysis of 28 Blood Biomarkers and Depression Reveals a Significant Association between Depression and Low Levels of Total Protein in Females

Introduction: Major depression (MD) is more common amongst women than men, and MD episodes have been associated with fluctuations in reproductive hormones amongst women. To investigate biological underpinnings of heterogeneity in MD, the associations between depression, stratified by sex and including perinatal depression (PND), and blood biomarkers, using UK Biobank (UKB) data, were evaluated, and extended to include the association of depression with biomarker polygenic scores (PGS), generated as proxy for each biomarker. Method: Using female (N = 39,761) and male (N = 38,821) UKB participants, lifetime MD and PND were tested for association with 28 blood biomarkers. A GWAS was conducted for each biomarker and genetic correlations with depression subgroups were estimated. Using independent data from the Australian Genetics of Depression Study, PGS were constructed for each biomarker, and tested for association with depression status (n [female cases/controls] = 9,006/6,442; n [male cases/controls] = 3,106/6,222). Regions of significant local genetic correlation between depression subgroups and biomarkers highlighted by the PGS analysis were identified. Results: Depression in females was significantly associated with levels of twelve biomarkers, including total protein (OR = 0.90, CI = [0.86, 0.94], p = 3.9 × 10−6) and vitamin D (OR = 0.94, CI = [0.90, 0.97], p = 2.6 × 10−4), and PND with five biomarker levels, also including total protein (OR = 0.88, CI = [0.81, 0.96], p = 4.7 × 10−3). Depression in males was significantly associated with levels of eleven biomarkers. In the independent Australian Genetics of Depression Study, PGS analysis found significant associations for female depression and PND with total protein (female depression: OR = 0.93, CI = [0.88, 0.98], p = 3.6 × 10−3; PND: OR = 0.91, CI = [0.86, 0.96], p = 1.1 × 10−3), as well as with vitamin D (female depression: OR = 0.93, CI = [0.89, 0.97], p = 2.0 × 10−3; PND: OR = 0.92, CI = [0.87, 0.97], p = 1.4 × 10−3). The male depression sample did not report any significant results, and the point estimate of total protein (OR = 0.98, CI = [0.92–1.04], p = 4.7 × 10−1) did not indicate any association. Local genetic correlation analysis highlighted significant genetic correlation between PND and total protein, located in 5q13.3 (rG = 0.68, CI = [0.33, 1.0], p = 3.6 × 10−4). Discussion and Conclusion: Multiple lines of evidence from genetic analysis highlight an association between total serum protein levels and depression in females. Further research involving prospective measurement of total protein and depressive symptoms is warranted.

Dietary flexibility of the greater bamboo lemur (Prolemur simus), a specialized feeder, in eastern Madagascar.

The degree of dietary flexibility in primates is species specific; some incorporate a wider array of resources than others. Extreme interannual weather variability in Madagascar results in seasonal resource scarcity which has been linked to specialized behaviors in lemurs. Prolemur simus, for example, has been considered an obligate specialist on large culm bamboo with >60% of its diet composed of woody bamboos requiring morphological and physiological adaptations to process. Recent studies reported an ever-expanding list of dietary items, suggesting that this species may not be an obligate specialist. However, long-term quantitative feeding data are unavailable across this species' range. To explore the dietary flexibility of P. simus, we collected data at two northern sites, Ambalafary and Sahavola, and one southern site, Vatovavy, from September 2010 to January 2016 and May 2017 to September 2018, respectively. In total, we recorded 4022 h of behavioral data using instantaneous sampling of adult males and females from one group in Ambalafary, and two groups each in Sahavola and Vatovavy. We recorded 45 plant species eaten by P. simus over 7 years. We also observed significant differences in seasonal dietary composition between study sites. In Ambalafary, bamboo was the most frequently observed resource consumed (92.2%); however, non-bamboo resources comprised nearly one-third of the diet of P. simus in Sahavola and over 60% in Vatovavy. Consumption of all bamboo resources increased during the dry season at Ambalafary and during the wet season at Vatovavy, but never exceeded non-bamboo feeding at the latter. Culm pith feeding was only observed at Ambalafary, where it was more common during the dry season. We identify P. simus as a bamboo facultative specialist capable of adjusting its feeding behavior to its environment, indicating greater dietary flexibility than previously documented, which may enable the species to survive in increasingly degraded habitats.

Paternal genetic structure analysis of the modern Han populations based on Y-SNP and Y-STR.

The Han populations represent the largest ethnic group in China. Previous studies have primarily focused on investigating their genetic origins, migration and integration, as well as paternal genetic relationships within specific regional Han populations. However, a comprehensive analysis of the global paternal genetic structure of Han populations is lacking. In this study, we performed Y-chromosome sequencing on 362 unrelated male samples from Chinese Han individuals collected from Qinghai, Sichuan and Liaoning provinces. We then integrated relevant data from reported studies. Our final dataset comprised 1830 samples from 16 Han populations across 15 provinces in China, encompassing information on 89 Y-SNPs and 16 Y-STRs. Statistical analyses were conducted to assess Y-STR haplotype diversity (HD) and Y-SNP haplogroup frequencies. Additionally, we employed principal component analysis (PCA), phylogenetic tree and haplotype network to explore genetic differentiation within Han populations and the genetic relationships between Han populations and ethnic minorities surrounding them. Our results demonstrated that the O-M175 haplogroup represents the predominant paternal lineage in Han populations, with frequencies ranging from 60.53% (Qinghai Han) to 92.7% (Guangdong Han). Moreover, the subclades downstream of O-M175 showed distinct regional variations in their distribution patterns. The O2-M122 haplogroup was prevalent in all Han populations and demonstrated a gradual decline in frequency from north to south. Conversely, the distribution frequency of the O1b-M268 haplogroup decreased from south to north, particularly showed significant presence among Han populations in the Lingnan region. Haplogroup O1a-M119 distributed more frequently in the central Han populations. Our findings revealed that Chinese Han populations can be categorized into three subgroups: northern, central, and southern. Notably, there were significant differences among Han in Qinghai and other regions. Regarding the genetic relationships between Han populations and surrounding ethnic minorities, we observed a closer genetic affinity between different Han populations, but northern Han demonstrated a stronger relationship with the Hui ethnic group, while southern Han exhibited a closer connection with the Gelao and Li ethnic groups. In summary, this study presented a systematic analysis of haplogroup distribution, genetic substructure of Han populations and genetic relationships between Han populations and surrounding ethnic minorities based on 89 Y-SNPs and 16 Y-STRs systematically. Our research supplemented valuable insights into population genetics and forensic genetics, and provided data support for the forensic application of Y chromosome. The integration of Y-SNP haplogroups with Y-STR haplotypes offers enhanced understanding of the genetic substructure within Han populations, which holds significance for both population genetics research and forensic science applications.

Cognitive and social-cognitive factors as mediators of aggression using structural equation modeling

ABSTRACT Violence and aggression continue to be both public health and economic concerns. In an effort to better understand, predict, and prevent violence and aggression, a number of models have been proposed that include both static and dynamic risk factors and indicators. Despite research demonstrating links between cognitive and social-cognitive factors with violence and aggression, their role in understanding violence is still unclear. The current study developed a multi-faceted model of aggression including social-cognitive, cognitive, personality, and psychiatric factors. A community, male sample (N = 1,192) collected through Amazon’s Mturk responded to a series of self-report measures and a cognitive task. Utilizing structural equation modeling (SEM), we created a latent variable path analysis model predicting aggression. Several important paths were significant including from entity theory to aggression, mediated by hostile attribution bias, schizotypy to aggression, mediated by both hostile attribution bias and disinhibition, substance use to aggression mediated by disinhibition, and psychopathy to aggression directly. This model provides a framework for future research that focuses on process factors of violence and aggression, including social-cognitive and cognitive, that may eventually prove valuable for risk reduction.

Population affinity estimation using pelvic measurements based on computed tomographic data acquired from Japanese and Western Australian populations

The present study analyzes morphological differences in the pelvis of Japanese and Western Australian individuals and investigates the feasibility of population affinity classification based on computed tomography (CT) data. The Japanese and Western Australian samples comprise CT scans of 207 (103 females; 104 males) and 158 (78 females; 80 males) adult individuals, respectively. Following volumetric reconstruction, a total of 19 pelvic landmarks were obtained on each sample, and 11 measurements, including two angles, were calculated. Machine learning methods (random forest modeling [RFM] and support vector machine [SVM]) were used to classify population affinity. Classification accuracy of the two-way models was approximately 80% for RFM: the two-way sex-specific and sex-mixed models for SVM achieved > 90% and > 85%, respectively. The sex-specific models had higher accurate classification rates than the sex-mixed models, except for the Japanese male sample. The classification accuracy of the four-way sex and population affinity model had an overall classification accuracy of 76.71% for RFM and 87.67% for SVM. All the correct classification rates were higher in the Japanese relative to the Western Australian sample. Our data suggest that pelvic morphology is sufficiently distinct between Japanese and Western Australian individuals to facilitate the accurate classification of population affinity based on measurements acquired in CT images. To the best of our knowledge, this is the first study investigating the feasibility of population affinity estimation based on CT images of the pelvis, which appears as a viable supplement to traditional approaches based on cranio-facial morphology.