Project description:The significant sex differences that exist in cancer mechanisms, incidence, and survival, have yet to impact clinical practice. We propose that one barrier to translation is that sex differences in cancer phenotypes resemble sex differences in height: highly overlapping, but distinct, male and female population distributions that vary continuously between female- and male- skewed extremes. A consequence of this variance is that sex-specific treatments are rendered unrealistic, and our translational goal should be adaptation of treatment to the variable sex-effect on targetable pathways. To develop a tool that could advance this goal, we applied a Bayesian Nearest Neighbor (BNN) analysis to 8370 cancer transcriptomes from 26 different adult and 4 different pediatric cancer types to establish patient-specific Transcriptomic Indices (TI). TI precisely positions a patient's whole transcriptome on axes of mechanistic phenotypes like cell cycle signaling and immunity that exhibit skewing in the cancer population relative to sex-identified extremes (poles). Importantly, the TI approach reveals that even when TI values are identical, underlying mechanisms in male and female individuals can differ in identifiable ways. Thus, cancer type, patient sex, and TI value provides a novel and patient- specific mechanistic identifier that can be used for precision cancer treatment planning.
Project description:The significant sex differences that exist in cancer mechanisms, incidence, and survival, have yet to impact clinical practice. We hypothesized that one barrier to translation is that sex differences in cancer phenotypes resemble sex differences in height: highly overlapping, but distinct, male and female population distributions that vary continuously between female- and male- biased extremes. A consequence of this variance is that sex-specific treatments are rendered unrealistic, and our translational goal should be adaptation of treatment to the unique mix of sex-biased mechanisms that are present in each patient. To develop a tool that could advance this goal, we applied a Bayesian Nearest Neighbor (BNN) analysis to 8370 cancer transcriptomes from 26 different adult and 4 different pediatric cancer types to establish patient-specific Transcriptomic Sex Indices (TSI). TSI precisely partitions an individual patient's whole transcriptome into female- and male- biased components such that cancer type, patient sex, and transcriptomics, provide a novel and patient-specific mechanistic identifier that can be used for sex-adapted, precision cancer treatment planning.
Project description:Because of the sex-gender differences that are shown in a diversity of physiological and psychological factors, it can be speculated that the clinical presentation of symptoms as well as treatment strategies in women and men with irritable bowel syndrome (IBS) may differ. Studies have revealed that IBS is more common in women than men. As for the IBS subtype, IBS with constipation is significantly more prevalent among women than men. Sex hormones and gender differences may play important roles in the pathophysiology of IBS. However, its pathophysiologic mechanisms still remain largely unknown, and therapeutic implications are limited. Moreover, women IBS patients have been reported to feel more fatigue, depression, anxiety, and lower quality of life than men IBS patients. Furthermore, there has been evidence of differences in the appropriate treatment efficacy to IBS in men and women, although relatively few men are enrolled in most relevant clinical trials. A more sex-gender-oriented approach in the medical care setting could improve understanding of heterogeneous patients suffering from IBS. An individualized and multicomponent approach including sex and gender issues might help improve the treatment of IBS.
Project description:This research addresses the long-standing debate about the determinants of sex/gender differences. Evolutionary theorists trace many sex/gender differences back to natural selection and sex-specific adaptations. Sociocultural and biosocial theorists, in contrast, emphasize how societal roles and social power contribute to sex/gender differences beyond any biological distinctions. By connecting two empirical advances over the past two decades-6-fold increases in sex/gender difference meta-analyses and in experiments conducted on the psychological effects of power-the current research offers a novel empirical examination of whether power differences play an explanatory role in sex/gender differences. Our analyses assessed whether experimental manipulations of power and sex/gender differences produce similar psychological and behavioral effects. We first identified 59 findings from published experiments on power. We then conducted a P-curve of the experimental power literature and established that it contained evidential value. We next subsumed these effects of power into 11 broad categories and compared them to 102 similar meta-analytic sex/gender differences. We found that high-power individuals and men generally display higher agency, lower communion, more positive self-evaluations, and similar cognitive processes. Overall, 71% (72/102) of the sex/gender differences were consistent with the effects of experimental power differences, whereas only 8% (8/102) were opposite, representing a 9:1 ratio of consistent-to-inconsistent effects. We also tested for discriminant validity by analyzing whether power corresponds more strongly to sex/gender differences than extraversion: although extraversion correlates with power, it has different relationships with sex/gender differences. These results offer novel evidence that many sex/gender differences may be explained, in part, by power differences.
Project description:Sex and gender disparities have been reported for different types of non-reproductive cancers. Males are two times more likely to develop kidney cancer than females and have a higher death rate. These differences can be explained by looking at genetics and genomics, as well as other risk factors such as hypertension and obesity, lifestyle, and female sex hormones. Examination of the hormonal signaling pathways bring further insights into sex-related differences. Sex and gender-based disparities can be observed at the diagnostic, histological and treatment levels, leading to significant outcome difference. This review summarizes the current knowledge about sex and gender-related differences in the clinical presentation of patients with kidney cancer and the possible biological mechanisms that could explain these observations. Underlying sex-based differences may contribute to the development of sex-specific prognostic and diagnostic tools and the improvement of personalized therapies.
Project description:Sex differences in the anatomy and physiology of the respiratory system have been widely reported. These intrinsic sex differences have also been shown to modulate the pathophysiology, incidence, morbidity, and mortality of several lung diseases across the life span. In this chapter, we describe the epidemiology of sex differences in respiratory diseases including neonatal lung disease (respiratory distress syndrome, bronchopulmonary dysplasia) and pediatric and adult disease (including asthma, cystic fibrosis, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, lung cancer, lymphangioleiomyomatosis, obstructive sleep apnea, pulmonary arterial hypertension, and respiratory viral infections such as respiratory syncytial virus, influenza, and SARS-CoV-2). We also discuss the current state of research on the mechanisms underlying the observed sex differences in lung disease susceptibility and severity and the importance of considering both sex and gender variables in research studies' design and analysis.
Project description:Data from treatment studies tends to show women are less likely to quit smoking than men, but these findings have been disputed, typically based on contradictory evidence from epidemiological investigations. The purpose of this review was to shed light on this conflict. We conducted a qualitative review in January 2016 to examine sources of variation in sex/gender differences for smoking cessation. We identified 214 sex/gender difference tests from 190 studies through Medline and studies were categorized into efficacy trials (k=37), effectiveness trials (k=77), prospective observational studies of cessation (k=40; current smokers transitioning to former smokers), prospective observational studies of relapse (k=6; former smokers transitioning to current smokers), cross-sectional investigations of former smoker prevalence (k=32), and community-based interventions (k=4). We also summarized evidence across time periods, countries, outcome assessments, study sample, and treatment. Evidence from efficacy and effectiveness trials, as well as prospective observational studies of relapse, demonstrated that women have more difficulty maintaining long-term abstinence than men. Findings from prospective observational studies and cross-sectional investigations were mixed and demonstrated that bio-psycho-social variation in samples across place and time may determine whether or not women or men are less likely to quit smoking. Based on these findings, we consider whether sex/gender differences in quitting meet criteria for a disparity and outline directions for further research.
Project description:There are important sex differences in the brain that seem to arise from biology as well as psychosocial influences. Sex differences in several aspects of human behavior and cognition have been reported. Gonadal sex steroids or genes found on sex chromosomes influence sex differences in neuroanatomy, neurochemistry and neuronal structure, and connectivity. There has been some resistance to accept that sex differences in the human brain exist and have biological relevance; however, a few years ago, it has been recommended by the USA National Institute of Mental Health to incorporate sex as a variable in experimental and clinical neurological and psychiatric studies. We here review the clinical literature on sex differences in pain and neurological and psychiatric diseases, with the aim to further stimulate interest in sexual dimorphisms in the brain and brain diseases, possibly encouraging more research in the field of the implications of sex differences for treating these conditions.
Project description:Nearly all diseases in humans, to a certain extent, exhibit sex differences, including differences in the onset, progression, prevention, therapy, and prognosis of diseases. Accumulating evidence shows that macroautophagy/autophagy, as a mechanism for development, differentiation, survival, and homeostasis, is involved in numerous aspects of sex differences in diseases such as cancer, neurodegeneration, and cardiovascular diseases. Advances in our knowledge regarding sex differences in autophagy-mediated diseases have enabled an understanding of their roles in human diseases, although the underlying molecular mechanisms of sex differences in autophagy remain largely unexplored. In this review, we discuss current advances in our insight into the biology of sex differences in autophagy and disease, information that will facilitate precision medicine.Abbreviations: AD: Azheimer disease; AMBRA1: autophagy and beclin 1 regulator 1; APP: amyloid beta precursor protein; AR: androgen receptor; AMPK: AMP-activated protein kinase; ATG: autophagy related; ATP6AP2: ATPase H+ transporting accessory protein 2; BCL2L1: BCL2 like 1; BECN1: beclin 1; CTSD: cathepsin D; CYP19A1: cytochrome P450 family 19 subfamily A member 1; DSD: disorders of sex development; eALDI: enhancer alternate long-distance initiator; ESR1: estrogen receptor 1; ESR2: estrogen receptor 2; FYCO1: FYVE and coiled-coil domain autophagy adaptor 1; GABARAP: GABA type A receptor-associated protein; GLA: galactosidase alpha; GTEx: genotype-tissue expression; HDAC6: histone deacetylase 6; I-R: ischemia-reperfusion; LAMP2: lysosomal associated membrane protein 2; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; m6A: N6-methyladenosine; MYBL2: MYB proto-oncogene like 2; PIK3C3: phosphatidylinositol 3-kinase catalytic subunit type 3; PSEN1: presenilin 1; PSEN2: presenilin 2; RAB9A, RAB9A: member RAS oncogene family; RAB9B, RAB9B: member RAS oncogene family; RAB40AL: RAB40A like; SF1: splicing factor 1; SOX9: SRY-box transcription factor 9; SRY: sex determining region Y; TFEB: transcription factor EB; ULK1: unc-51 like autophagy activating kinase 1; UVRAG: UV radiation resistance associated; VDAC2: voltage dependent anion channel 2; WDR45: WD repeat domain 45; XPDS: X-linked parkinsonism and spasticity; YTHDF2: YTH N6-methyladenosine RNA binding protein 2.