The within-sample relative expression orderings (REOs) of genes, which are stable qualitative transcriptional characteristics, can provide abundant information for a disease. Methods based on REO comparisons have been proposed for identifying differentially expressed genes (DEGs) at the individual level and for detecting disease-associated genes based on one-phenotype disease data by reusing data of normal samples from other sources. Here, we evaluated the effects of common potential confounding factors, including age, cigarette smoking, sex, and race, on the REOs of gene pairs within normal lung tissues transcriptome. Our results showed that age has little effect on REOs within lung tissues. We found that about 0.23% of the significantly stable REOs of gene pairs in nonsmokers' lung tissues are reversed in smokers' lung tissues, introduced by 344 DEGs between the two groups of samples (RankCompV2, FDR <0.05), which are enriched in metabolism of xenobiotics by cytochrome P450, glutathione metabolism, and other pathways (hypergeometric test, FDR <0.05). Comparison between the normal lung tissue samples of males and females revealed fewer reversal REOs introduced by 24 DEGs between the sex groups, among which 19 DEGs are located on sex chromosomes and 5 DEGs involving in spermatogenesis and regulation of oocyte are located on autosomes. Between the normal lung tissue samples of white and black people, we identified 22 DEGs (RankCompV2, FDR <0.05) which introduced a few reversal REOs between the two races. In summary, the REO-based study should take into account the confounding factors of cigarette smoking, sex, and race.

To better understand the differences in clinicopathological features and prognosis between male breast cancer (MBC) and female breast cancer (FBC).

In prey species, vigilance is an important part of the decision making process related to predation risk effects. Therefore, understanding the mechanisms shaping vigilance behavior provides relevant insights on factors influencing individual fitness. We investigated the role of extrinsic and intrinsic factors on vigilance behavior in Mediterranean mouflon (Ovis gmelini musimon×Ovis sp.) in a study site spatially and temporally contrasted in human pressures. Both sexes were less vigilant in the wildlife reserve compared to surrounding unprotected areas, except for males during the hunting period. During this period, males tended to be less strictly restricted to the reserve than females what might lead to a pervasive effect of hunting within the protected area, resulting in an increase in male vigilance. It might also be a rutting effect that did not occur in unprotected areas because males vigilance was already maximal in response to human disturbances. In both sexes, yearlings were less vigilant than adults, probably because they traded off vigilance for learning and energy acquisition and/or because they relied on adult experience present in the group. Similarly, non-reproductive females benefited of the vigilance effort provided by reproductive females when belonging to the same group. However, in the absence of reproductive females, non-reproductive females were as vigilant as reproductive females. Increasing group size was only found to reduce vigilance in females (up to 17.5%), not in males. We also showed sex-specific responses to habitat characteristics. Females increased their vigilance when habitat visibility decreased (up to 13.8%) whereas males increased their vigilance when feeding on low quality sites, i.e., when concomitant increase in chewing time can be devoted to vigilance with limited costs. Our global approach was able to disentangle the sex-specific sources of variation in mouflon vigilance and stressed the importance of reserves in managing and conserving wild sheep populations.

Deciphering the biological mechanisms underlying social behavior in animal models requires standard behavioral paradigms that can be unbiasedly employed in an observer- and laboratory-independent manner. During the past decade, the three-chamber test has become such a standard paradigm used to evaluate social preference (sociability) and social novelty preference in mice. This test suffers from several caveats, including its reliance on spatial navigation skills and negligence of behavioral dynamics.

Female sex workers (FSWs) are key groups in the transmission of sexual transmitted infections (STI), and vaginal microbiome variations play an important role in transmission. We aimed to explore the characteristics of vaginal microbiome among FSWs.

The aim of this study was to determine how maternal undernutrition during pregnancy and offspring birth-weight can affect the postnatal development of offspring under farm conditions, which may lead to consequences in its meat and carcass quality. The current study involved a total of 80 litters from Iberian sows fed a diet fulfilling daily requirements (n = 47; control) or providing 70% daily requirements (n = 33; underfed) from d 38 to d 90 of gestation when fetal tissue development begins. After birth, piglets born live were classified as low birth-weight (LBW; < 1 kg) and normal birth-weight (NBW; ≥1 kg). During the growing phase, 240 control and 230 underfed pigs (50% males and females) distributed by BW category and sex were studied until the slaughter.

Background: Coronavirus disease-2019 (COVID-19) epidemic is spreading globally. Sex differences in the severity and mortality of COVID-19 emerged. This study aims to describe the impact of sex on outcomes in COVOD-19 with a special focus on the effect of estrogen. Methods: We performed a retrospective cohort study which included 413 patients (230 males and 183 females) with COVID-19 from three designated hospitals in China with a follow up time from January 31, 2020, to April 17, 2020. Women over 55 were considered as postmenopausal patients according to the previous epidemiological data from China. The interaction between age and sex on in-hospital mortality was determined through Cox regression analysis. In addition, multivariate Cox regression models were performed to explore risk factors associated with in-hospital mortality of COVID-19. Results: Age and sex had significant interaction for the in-hospital mortality (P < 0.001). Multivariate Cox regression showed that age (HR 1.041, 95% CI 1.009-1.073, P = 0.012), male sex (HR 2.033, 95% CI 1.007-2.098, P = 0.010), the interaction between age and sex (HR 1.118, 95% CI 1.003-1.232, P = 0.018), and comorbidities (HR 9.845, 95% CI 2.280-42.520, P = 0.002) were independently associated with in-hospital mortality of COVID-19 patients. In this multicentre study, female experienced a lower fatality for COVID-19 than male (4.4 vs. 10.0%, P = 0.031). Interestingly, stratification by age group revealed no difference in-hospital mortality was noted in women under 55 compared with women over 55 (3.8 vs. 5.2%, P = 0.144), as well as in women under 55 compared with the same age men (3.8 vs. 4.0%, P = 0.918). However, there was significantly difference in women over 55 with men of the same age group (5.2 vs. 21.0%, P = 0.007). Compared with male patients, female patients had higher lymphocyte (P < 0.001) and high-density lipoprotein (P < 0.001), lower high sensitive c reaction protein level (P < 0.001), and lower incidence rate of acute cardiac injury (6.6 vs. 13.5%, P = 0.022). Conclusion: Male sex is an independent risk factor for COVID-19 in-hospital mortality. Although female mortality in COVID-19 is lower than male, it might not be directly related to the effect of estrogen. Further study is warranted to identify the sex difference in COVID-19 and mechanisms involved.

Background: Wilson's disease (WD) is an inborn copper metabolism disease. Sex differences in clinical features of WD patients have been reported; however, the effect of sex on brain MRI is still unclear, especially for Chinese WD patients. Therefore, we aimed to examine sex differences in clinical correlates and brain MRI changes in WD patients in a Chinese Han population. Methods: 535 WD patients were enrolled and underwent MRI scanning. These patients were subdivided by the clinical symptoms, Kayser-Fleischer (K-F) rings, laboratory tests and sex. The mean age of onset and diagnosis, disease latency, localization of brain MRI lesions, and the level of copper metabolism were compared between male and female patients. Results: The neuropsychiatric form (452 and 84.5%) was the most common subtype. Compared to female patients, male patients had a higher percentage in three clinical forms: neuropsychiatric form (263 and 58.2%), hepatic form (41 and 59.4%), and presymptomatic form (10 and 71.4%). In the neuropsychiatric form, male patients had the earlier age of onset and definitive diagnosis, and shorter time of disease latency than female patients. Putamen was the most common site for lesions in brain MRI of three groups. In the hepatic form, more male patients showed the ventricular widening than female patients (14/41 vs. 3/28; p < 0.05). The level of serum ceruloplasmin and copper of WD patients with neuropsychiatric form was higher than that of male patients with hepatic or presymptomatic form. In women, however, patients of presymptomatic form have the highest level of the ceruloplasmin, and the level of serum copper in hepatic patients was highest. Conclusion: Our findings suggest sex differences in the percentage of three clinical forms. Meanwhile, the mean age of onset and diagnosis of female was higher than male, also happened in the disease latency. Only in the hepatic form, there was a sex difference in the ventricular widening.

Background Studies demonstrated sex differences in outcomes following acute myocardial infarction, with women more likely to develop heart failure (HF). Sacubitril/valsartan has been shown to reduce cardiovascular death and HF hospitalizations in patients with HF with reduced ejection fraction. Methods and Results A total of 5661 patients (1363 women [24%]) with acute myocardial infarction complicated by reduced left ventricular ejection fraction (≤40%), pulmonary congestion, or both and ≥1 of 8 risk-augmenting factors were randomized to receive sacubitril/valsartan or ramipril. The primary outcome was cardiovascular death or incident HF. Baseline characteristics, clinical outcomes, and safety events were compared according to sex, a prespecified subgroup. Female participants were older and had more comorbidities. After multivariable adjustment, women and men were at similar risks for cardiovascular death or all-cause death. Women were more likely to have first HF hospitalization (hazard ratio [HR], 1.34 [95% CI, 1.05-1.70]; P=0.02) and total HF hospitalizations (HR, 1.39 [95% CI, 1.05-1.84]; P=0.02). Sex did not significantly modify the treatment effect of sacubitril/valsartan compared with ramipril on the primary outcome (P for interaction=0.11). Conclusions In contemporary patients who presented with reduced left ventricular ejection fraction, pulmonary congestion, or both, following acute myocardial infarction, women had a higher incidence of HF during follow-up. Sex did not modify the treatment effect of sacubitril/valsartan relative to ramipril. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02924727.

Androgens play key roles in the morphological specification of male type sex attractive and reproductive organs, whereas little is known about the developmental mechanisms of such secondary sex characters. Medaka offers a clue about sexual differentiation. They show a prominent masculine sexual character for appendage development, the formation of papillary processes in the anal fin, which has been induced in females by exogenous androgen exposure. This current study shows that the development of papillary processes is promoted by androgen-dependent augmentation of bone morphogenic protein 7 (Bmp7) and lymphoid enhancer-binding factor-1 (Lef1). Androgen receptor (AR) subtypes, ARα and ARβ, are expressed in the distal region of outgrowing bone nodules of developing papillary processes. Development of papillary processes concomitant with the induction of Bmp7 and Lef1 in the distal bone nodules by exposure to methyltestosterone was significantly suppressed by an antiandrogen, flutamide, in female medaka. When Bmp signaling was inhibited in methyltestosterone-exposed females by its inhibitor, dorsomorphin, Lef1 expression was suppressed accompanied by reduced proliferation in the distal bone nodules and retarded bone deposition. These observations indicate that androgen-dependent expressions of Bmp7 and Lef1 are required for the bone nodule outgrowth leading to the formation of these secondary sex characteristics in medaka. The formation of androgen-induced papillary processes may provide insights into the mechanisms regulating the specification of sexual features in vertebrates.

Sex-determining region Y-box 30 (SOX30) suppresses progression of several cancers, whereas its role in breast cancer is unclear. Therefore, we aimed to determine the correlation of SOX30 with tumor characteristics and prognosis in breast cancer patients.

Yunnan has been severely affected by HIV/AIDS in China. Recently, the reported prevalence of HIV-1 among men who have sex with men (MSM) in Yunnan was high in China. To monitor dynamic HIV-1 epidemic among Yunnan MSM, HIV-1 genetic characteristics and transmitted drug resistance (TDR) were investigated.

Diagnosis and management strategy of disorders of sex development (DSD) are difficult and various due to heterogeneous phenotype and genotype. Under widespread use of genomic sequencing technologies, multiple genes and mechanisms have been identified and proposed as genetic causes of 46,XY DSD. In this study, 178 46,XY DSD patients were enrolled and underwent gene sequencing (either whole-exome sequencing or targeted panel gene sequencing). Detailed clinical phenotype and genotype information were summarized which showed that the most common clinical manifestations were micropenis (56.74%, 101/178), cryptorchidism (34.27%, 61/178), and hypospadias (17.42%, 31/178). Androgen synthesis/action disorders and idiopathic hypogonadotropic hypogonadism were the most frequent clinical diagnoses, accounting, respectively, for 40.90 and 21.59%. From all next-generation sequencing results, 103 candidate variants distributed across 32 genes were identified in 88 patients. The overall molecular detection rate was 49.44% (88/178), including 35.96% (64/178) pathogenic/likely pathogenic variants and 13.48% (24/178) variants of uncertain significance. Of all, 19.42% (20/103) variants were first reported in 46,XY DSD patients. Mutation c.680G>A (p.R227Q) on SRD5A2 (steroid 5-alpha-reductase 2) (36.67%, 11/30) was a hotspot mutation in the Chinese population. Novel candidate genes related to DSD (GHR (growth hormone receptor) and PHIP (pleckstrin homology domain-interacting protein)) were identified. Overall, this was a large cohort of 46,XY DSD patients with a common clinical classification and phenotype spectrum of Chinese patients. Targeted gene panel sequencing covered most of the genes contributing to DSD, whereas whole-exome sequencing detected more candidate genes.

It is becoming increasingly clear that robust sex differences exist in the processing of acute and chronic pain in both rodents and humans. However, the underlying mechanism has not been well characterized. The dorsal horn of the lumbar spinal cord is the fundamental building block of ascending and descending pain pathways. It has been shown that numerous neurotransmitter and neuromodulator systems in the spinal cord, including the endocannabinoid system and its main receptor, the cannabinoid 1 receptor (CB1 R), play vital roles in processing nociceptive information. Our previous findings have shown that CB1 R mRNA is widely expressed in the brain in sex-dependent patterns. However, the sex-, lamina-, and cell-type-specific characteristics of CB1 R expression in the spinal cord have not been fully described. In this study, the CB1 R-iCre-EGFP mouse strain was generated to label and identify CB1 R-positive (CB1 RGFP ) cells. We reported no sex difference in CB1 R expression in the lumbar dorsal horn of the spinal cord, but a dynamic distribution within superficial laminae II and III in female mice between estrus and nonestrus phases. Furthermore, the cell-type-specific CB1 R expression pattern in the dorsal horn was similar in both sexes. Over 50% of CB1 RGFP cells were GABAergic neurons, and approximately 25% were glycinergic and 20-30% were glutamatergic neurons. The CB1 R-expressing cells also represented a subset of spinal projection neurons. Overall, our work indicates a highly consistent distribution pattern of CB1 RGFP cells in the dorsal horn of lumbar spinal cord in males and females.

Bird plumage is often very colorful and can communicate the quality of the bearer to conspecifics. These plumage-based signals of quality are composed of multiple pigments (e.g., melanin and carotenoids). Therefore, sex and age classes, which often show marked differences in plumage coloration, may have different dietary needs for the different plumage components and this might promote preferences for different dietary niches at different molting stages. However, no study has addressed the role that changes in niche use play in the expression of multiple component plumage signals in birds. We used stable isotope analysis to test the hypothesis that niche use is related to age and sex and to differently cultured plumage patches, yellow carotenoid-based and black melanin-based, in great tits Parus major. We recorded high niche overlap between plumage patches, although δ15N was higher in black than yellow plumage. Niche overlap was relatively low for age classes and relatively high for sex classes, and age classes showed a contrasting pattern of niche overlap between carotenoid- and melanin-based plumages. Moreover, δ13C, but not δ15N, had a significant negative relationship with carotenoid-based plumage, which was only apparent in juveniles. Taken together, our results demonstrate that niche use had a moderate influence on plumage coloration characteristics of great tit individuals, mostly associated with δ13C rather than with δ15N and with age rather than with sex. Therefore, our study is significant because it confirms the relevance of niche use during ornament production in free-living birds.

To explore how a genetically-influenced characteristic (the level of response to alcohol [LR]), ethnicity, and sex relate to environmental and attitudinal characteristics (peer drinking [PEER], drinking to cope [COPE], and alcohol expectancies [EXPECT]) regarding future alcohol-related blackouts (ARBs).

Epidemiology of drug resistant HIV has focused on trends and less attention has been given to identification of factors, especially behaviors including substance use, in acquisition of drug-resistant HIV. From 2009 to 2012 The Metromates Study enrolled and followed for one year men who have sex with men (MSM) seeking testing for HIV in a community clinic in Los Angeles assessing those testing positive for acute and recent HIV infection. Behavioral data were collected via Computer-Assisted Self-Interview from 125 classified as newly HIV infected and 91 as chronically infected (newly HIV-diagnosed); specimens were available and viable for resistance testing for 154 of the 216 HIV positives with new diagnoses. In this community clinic we found prevalence of resistance among MSM with new HIV-diagnosis was 19.5% (n = 30/154) with no difference by recency of HIV infection. Sexual partnership characteristics were associated with resistance; those who reported transgendered sex partners had a higher prevalence of resistance as compared to those who did not report transgendered sex partners (40% vs. 17%; p value = 0.04), while those who reported having a main partner had a lower prevalence of drug resistance (12% vs. 24%; p value = 0.07). In multivariable analyses adjusting for HIV recency and antiviral use, reporting a main partner decreased odds [adjusted odds ratio (AOR) 0.34; 95% confidence interval (CI) 0.13-0.87], reporting a transgendered partnered increased odds (AOR = 3.37; 95% CI 0.95-12.43); and being African American increased odds of drug resistance (AOR = 5.63, 95%CI 1.41-22.38). This suggests African American MSM and TG individuals in Los Angeles represent pockets of exceptional risk that will require special approaches to prevention and care to enhance their own health and reduce their likelihood to support transmission of drug resistance in the US.

The coronavirus disease 2019 (COVID-19) became a global pandemic. Males, compared to females, seem to be more susceptible to COVID-19, but related evidence is scarce, especially in severe patients. We explored sex differences in clinical characteristics and potential risk factors for mortality in severe COVID-19 patients. In this retrospective cohort study, we included all severe COVID-19 patients admitted to Eastern Renmin Hospital of Wuhan University, Wuhan, China, with a definitive clinical outcome as of Apr 10, 2020. Of the included 651 patients, 332 were male, and 319 were female. Males and females did not differ in age and underlying comorbidities. Males were more likely than females to report fever and develop serious complications, including acute respiratory distress syndrome, secondary infection, acute cardiac injury, coagulopathy, acute kidney injury and arrhythmia. Further, males had much higher mortality relative to females. Multivariable regression showed neutrophilia (odds ratio 6.845, 95% CI 1.227-38.192, p=0.028), thrombocytopenia (19.488, 3.030-25.335, p=0.002), hypersensitive troponin I greater than 0.04 pg/mL (6.058, 1.545-23.755, p=0.010), and procalcitonin greater than 0.1 ng/mL (6.350, 1.396-28.882, p=0.017) on admission were associated with in-hospital death. With either of these risk factors, the cumulative survival rate was relatively lower in males than in females. In conclusion, males are more likely than females to develop serious complications and progress to death. The potential risk factors of neutrophilia, thrombocytopenia, hypersensitive troponin I greater than 0.04 pg/mL and procalcitonin more than 0.1 ng/mL may help clinicians to identify patients with poor outcomes at an early stage, especially in males.

The objective of this study was to analyze the thickness and medullation characteristics of the wool of a herd of Huacaya alpacas kept in Poland. Wool samples were collected from 36 adult alpacas, including 22 females and 14 males. Light (15 animals) and dark (21 animals) color varieties of wool were considered in this research. A projection microscope was used to measure the fiber diameter and assess the medullation. Each fiber was categorized according to the medulla as a non-medullated, discontinuous medullated or continuous medullated fiber. The mean fiber diameter (MFD), standard deviation (SD), coefficient of variation (CV), comfort factor (CF) and prickling factor (PF) were determined for each sample. The MFD, SD and CV were also determined for the abovementioned fiber categories. The mean fiber diameter of all alpacas tested was 25.31  µ m . The CF and PF were 77.79 % and 22.21 %, respectively. The medullation percentage in the wool of the study alpacas was 68.91 %. The mean fiber diameter was larger in males ( P < 0.05 ) than in females. There were no differences between males and females in terms of the proportion of fibers with a diameter  <  30  µ m (CF) and  >  30  µ m (PF). The non-medullated fibers in the wool of females were thinner ( P < 0.05 ) than in the wool of males. The wool of males also had a larger degree of medullation. Light wool was thinner ( P < 0.05 ) than dark wool. The discontinuous and the continuous medullated fibers were thicker ( P < 0.05 ) in dark wool than in light wool. In dark wool, the share of discontinuous fibers was higher ( P < 0.05 ) and the share of the non-medullated fibers was lower ( P < 0.05 ) than in light wool. The presence of various types of medulla or the absence of medulla was noted in fibers with smaller and larger diameters, regardless of the sex of the animals or the color of the wool.

Steroidogenic factor 1 (SF-1/NR5A1) is essential for human sex development. Heterozygous NR5A1/SF-1 variants manifest with a broad range of phenotypes of differences of sex development (DSD), which remain unexplained.