• Humans
• Alzheimer Disease/therapy
• Alzheimer Disease/diagnosis
• Alzheimer Disease/epidemiology
• Female
• Sex Characteristics
• Male
• Biomarkers
• Sex Factors

• Bioluminescence
• Fas expression
• Gemcitabine
• Immunocompetent preclinical model
• Inhaled chemotherapy
• Osteosarcoma lung metastasis
• Pulmonary drug delivery

• Animals
• Lung Neoplasms/secondary
• Lung Neoplasms/drug therapy
• Osteosarcoma/drug therapy
• Osteosarcoma/pathology
• Female
• Male
• Mice, Inbred BALB C
• Bone Neoplasms/pathology
• Bone Neoplasms/drug therapy
• Cell Line, Tumor
• Disease Models, Animal
• Mice
• Deoxycytidine/analogs & derivatives
• Deoxycytidine/administration & dosage
• Deoxycytidine/pharmacology
• Gemcitabine
• Antimetabolites, Antineoplastic/administration & dosage
• Antimetabolites, Antineoplastic/pharmacology
• Antimetabolites, Antineoplastic/therapeutic use
• Sex Factors
• Humans

• Blood-brain barrier
• GSK-3β
• Gut-brain axis
• Neuroinflammation
• Olfactory discrimination
• Preclinical Alzheimer’s disease
• Pretangle tau
• Probiotics
• Spatial learning

• Animals
• Probiotics/pharmacology
• Probiotics/administration & dosage
• Probiotics/therapeutic use
• Alzheimer Disease/metabolism
• Alzheimer Disease/pathology
• Alzheimer Disease/diet therapy
• Rats
• tau Proteins/metabolism
• tau Proteins/genetics
• Male
• Disease Models, Animal
• Female
• Cognition/drug effects
• Cognition/physiology
• Gastrointestinal Microbiome
• Rats, Transgenic

• PJT-169197 CIHR
• Canadian Institutes of Health Research

• acute kidney injury
• autoimmune disease
• chronic kidney disease
• inflammation
• sex differences
• sex hormones

• Humans
• Female
• Kidney Diseases/physiopathology
• Kidney Diseases/epidemiology
• Kidney/physiopathology
• Animals
• Male
• Sex Factors
• Sex Characteristics
• Health Status Disparities

• AADAC
• Androgen
• CES2
• Gender
• Platelet
• Sex
• Vicagrel
• p38 MAPK

• Animals
• Female
• Male
• Mice
• Androgens/metabolism
• Androgens/pharmacology
• Blood Platelets/metabolism
• Blood Platelets/drug effects
• Sex Characteristics
• Ovariectomy
• Orchiectomy
• Mice, Inbred C57BL
• p38 Mitogen-Activated Protein Kinases/metabolism
• p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors
• Carboxylic Ester Hydrolases/metabolism
• Carboxylic Ester Hydrolases/genetics
• Pyridines/pharmacology
• Phenylacetates
• Thiophenes

• clinical
• epidemiology
• gender
• preclinical
• sex

• Gender
• Pharmacology
• Sex

• Mexico
• age-standardized incidence rate
• leukemia
• leukemia subtypes
• prevalence

• Humans
• Mexico/epidemiology
• Male
• Female
• Child
• Adolescent
• Adult
• Child, Preschool
• Middle Aged
• Incidence
• Aged
• Infant
• Leukemia/epidemiology
• Leukemia/classification
• Young Adult
• Prevalence
• Age Factors
• Aged, 80 and over
• Registries/statistics & numerical data

• Alzheimer’s disease
• Parkinson’s disease
• experimental models
• neurodegeneration
• neuroinflammation
• neurotoxic agents
• neurotransmission

• Alzheimer’s disease
• Frontotemporal dementia
• MAPT
• biomarkers
• dementia
• microRNA
• microRNA-capture affinity technology

• University of Trento

• pharmacology
• preclinical experimentation
• sex differences

• Biomedical
• Clinical
• Female
• Male
• Pharmacology
• Product surveillance postmarketing
• Sex characteristics
• Translational Science

Severe outcomes from SARS-CoV-2 infection are highly associated with preexisting comorbid conditions like hypertension, diabetes, and obesity. We utilized the diet-induced obesity (DIO) model of metabolic dysfunction in K18-hACE2 transgenic mice to model obesity as a COVID-19 comorbidity. Female DIO, but not male DIO mice challenged with SARS-CoV-2 were observed to have shortened time to morbidity compared to controls. Increased susceptibility to SARS-CoV-2 in female DIO was associated with increased viral RNA burden and interferon production compared to males. Transcriptomic analysis of the lungs from all mouse cohorts revealed sex- and DIO-associated differential gene expression profiles. Male DIO mice after challenge had decreased expression of antibody-related genes compared to controls, suggesting antibody producing cell localization in the lung. Collectively, this study establishes a preclinical comorbidity model of COVID-19 in mice where we observed sex- and diet-specific responses that begin explaining the effects of obesity and metabolic disease on COVID-19 pathology.

•

Transcriptomic analysis of infected lungs revealed unique sex-dependent differences

• Human metabolism
• Virology

• appetite
• chemogenetic
• circuit manipulation
• obesity
• optogenetic

Colorectal cancer (CRC) incidence and mortality seems to be lower in women than in men. The present study aims to evaluate the impact of gender on CRC diagnosis, treatment, and survival. This is a retrospective cohort study based on a single-center dataset of CRC patients from the University Hospital of Trieste (Italy). Data of 1796 consecutive CRC patients referred to our center from November 11th, 2004, to December 31st, 2017, were analyzed. Right-sided carcinomas are more frequent in women than in men; furthermore, women had a lower surgical complication rate. Men showed a higher 5- and 10-year mortality. This survival benefit for women was observed independently of the tumor localization. The 5-year hazard ratio (HR) for women vs men was 0.776 (p 0.003), and after 10-year 0.816 (p 0.017). Regarding the disease-free survival (DFS), 5 and 10-year HR was 0.759 (p 0.034) and 0.788 (p 0.07), respectively. On multivariable analysis, respecting tumor localization, the odds of female gender were higher than man with right colon disease. Male gender was more independently associated with age at the surgery time. Women survival advantage was higher than men, except for patients older than 80. Surgical outcome and survival after CRC surgical treatment seem to be gender related. For this reason, gender could play an important role in CRC diagnosis and therapy, allowing an earlier diagnosis in women.

• Colorectal cancer
• Colorectal surgery
• Gender differences
• Prevention
• Survival

• childhood cancer
• global burden of disease
• global health
• public health
• secular trends

• Child
• Child, Preschool
• Global Burden of Disease
• Humans
• Incidence
• Leukemia
• Male
• Quality-Adjusted Life Years
• Testicular Neoplasms

• National Natural Science Foundation of China
• China Scholarship Council

• adverse effects
• cancer du pancreas
• chemotherapy
• chimiothérapie
• différences entre les sexes
• drugs toxicity
• effets indésirables
• gender differences
• pancreatic carcinoma
• toxicité médicamenteuse

• Antineoplastic Combined Chemotherapy Protocols/adverse effects
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Female
• Humans
• Male
• Pancreatic Neoplasms/drug therapy
• Quality of Life
• Survival Rate
• Pancreatic Neoplasms

Given the biological differences between females and males, sex-specific evaluations should be carried out to obtain better cancer prevention, diagnosis, and treatment strategies. To this purpose, our aim was to evaluate sex differences for toxicity in a cohort of colorectal cancer (CRC) patients undergoing chemotherapy.

We performed a retrospective study in 329 CRC patients. Differences between males and females were tested performing the Mann-Whitney U test or the Fisher exact test. Multivariate logistic regression models were computed to evaluate the association between sex and risk of chemotherapy agent-related toxicity.

According association sex toxicity, significant differences were observed in the median number of episodes of nausea (p = 0.044), vomit (p = 0.007), heartburn (p = 0.022), thrombocytopenia (p = 0.005), mucositis (p = 0.024). Moreover, statistically significant differences between males and females were observed in the distribution of the highest toxicity grades of nausea (p = 0.024), heartburn (p = 0.016), and thrombocytopenia (p = 0.034). Females have an increased risk of vomit (p = 0.002), alopecia (p = 0.035), heartburn (p = 0.005), mucositis (p = 0.003), and lower risk for thrombocytopenia (p = 0.005).

According to the association of sex chemotherapy agent-related toxicities, females resulted on average at a significant increased risk of more common adverse events (constipation, dysgeusia, alopecia, heartburn, vomit, asthenia, nausea, pain events, and mucositis). Sex-tailored CRC chemotherapy treatment is necessary to obtain efficacy avoiding toxicity, based on patients’ biological and genetic characteristics, a vision that would change CRC setting, a stable disease but still orphan of a real tailored approach.

The online version contains supplementary material available at 10.1007/s00228-022-03298-y.

• Adverse events
• Chemotherapy
• Colorectal cancer
• Personalized medicine
• Sex

In radiotherapy for rectal cancer, the treatment is identical for women and men. In recent years, the question has arisen whether there are gender differences in radiochemotherapy. We have investigated, in detail, differences between men and women, especially with regard to radiation sensitivity. We found no evidence for a difference in radiosensitivity between the sexes. Nevertheless, during radiochemotherapy, women experienced increased impairments in the quality of life, which, however, are restored in the subsequent period. One possibility is an increased sensitivity of women to chemotherapy.

Gender is increasingly recognized as an important factor in medicine, although it has long been neglected in medical research in many areas. We have studied the influence of gender in advanced rectal cancer with a special focus on radiosensitivity. For this purpose, we studied a cohort of 495 men (84.1% ≥ T3, 63.6% N1, 17.6%, M1) and 215 women (84.2% ≥ T3, 56.7% N1, 22.8%, M1) who all suffered from advanced rectal cancer and were treated with radiochemotherapy. The energy deposited, DNA double-strand break (dsb) repair, occurrence of chromosomal aberrations, duration of therapy, tumor regression and tumor-infiltrating lymphocytes, laboratory parameters, quality of life and survival were assessed. The residual DNA dsb damage 24 h after irradiation in lymphocytes was identical in both sexes. Furthermore, chromosomal aberrations accurately reflecting radiosensitivity, were similar in both sexes. There were no gender-dependent differences in tumor regression, tumor-infiltrating lymphocytes and outcome indicating no differences in the radiosensitivity of cancer cells. The irradiated tumor volume in women was slightly lower than in men, related to body weight, no difference was observed. However, when the total energy deposited was calculated and related to the body weight, women were exposed to higher amounts of ionizing radiation. During radiochemotherapy, decreases in blood lymphocyte counts and albumin and several quality-of-life parameters such as nausea and vomiting, loss of appetite, and diarrhea were significantly worse in women. There is no difference in radiation sensitivity between men and women in both normal tissue and tumors. During radiochemotherapy, the quality of life deteriorates more in women than in men. However, women also recover quickly and there are no long-term differences in quality of life.

• DNA double-strand breaks
• blood values
• deposited energy
• gender
• quality of life
• radiochemotherapy
• radiosensitivity
• rectal cancer

• Biases
• Diferencias según sexo
• Educación médica
• Gender
• Género
• Leucemia
• Leukemia
• Medical education
• Sesgos
• Sex-differences

• anthropometric measures
• blood test
• health
• heart rate variability
• physiological network
• sex differences
• sexual dimorphism

Sex is a significant variable in the prevalence and incidence of neurological disorders. Sex differences exist in neurodegenerative disorders (NDs), where sex dimorphisms play important roles in the development and progression of Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. In the last few years, some sex specific biomarkers for the identification of NDs have been described and recent studies have suggested that microRNA (miRNA) could be included among these, as influenced by the hormonal and genetic background. Failing to consider the possible differences between males and females in miRNA evaluation could introduce a sex bias in studies by not considering some of these sex-related biomarkers. In this review, we recapitulate what is known about the sex-specific differences in peripheral miRNA levels in neurodegenerative diseases. Several studies have reported sex-linked disparities, and from the literature analysis miR-206 particularly has been shown to have a sex-specific involvement. Hopefully, in the near future, patient stratification will provide important additional clues in diagnosis, prognosis, and tailoring of the best therapeutic approaches for each patient. Sex-specific biomarkers, such as miRNAs, could represent a useful tool for characterizing subgroups of patients.

• Alzheimer’s disease
• Parkinson’s disease
• amyotrophic lateral sclerosis
• biomarkers
• microRNAs
• neurodegenerative diseases
• sex differences

• Biomarkers/analysis
• Humans
• MicroRNAs/analysis
• MicroRNAs/genetics
• Neurodegenerative Diseases/diagnosis
• Neurodegenerative Diseases/genetics
• Sex Factors

• Clinical trial
• Gender equity
• Sex
• Translational medical research

• axe cœur–cerveau
• cardiovascular disease
• cognitive dysfunction
• dysfonctionnement cognitif
• epigenetics
• female
• femelle
• heart–brain axis
• maladies cardiovasculaires
• épigénétique

• Humans
• Brain/physiopathology
• Brain/metabolism
• Animals
• Heart/physiopathology
• Sex Characteristics
• Female
• Male
• Sex Factors
• Risk Factors

• Adolescent health
• Asthma
• COVID-19
• Chronic kidney disease
• Gender medicine
• Guidelines and policy
• Model
• Obesity
• Risk factors

• Genotype-Tissue Expression
• RNA-seq
• The Cancer Genome Atlas
• differential expression
• gastric cancer
• gender differences
• gene co-expression networks
• thyroid cancer

• Apoptosis
• Mitochondria
• Stroke

• Animals
• Brain Ischemia/blood
• Brain Ischemia/pathology
• Humans
• Mice
• Mitochondria/metabolism
• Rats
• Stroke/blood
• Stroke/pathology

Colorectal carcinomas represent the third most common cause of cancer-related deaths in Germany. Although the incidence is significantly higher in men compared with women and gender is a well-established crucial factor for outcome in other diseases, detailed gender comparisons for colon cancer are lacking.

This retrospective population-based cohort study included all patients diagnosed with colon cancer in Germany between 2000 and 2016 who were included in the common dataset of colorectal cancer patients from the quality conference of the German Cancer Society. We compared clinical, histopathological, and therapeutic characteristics as well as overall and recurrence-free survival.

A total of 185,967 patients were included in the study, of which 85,685 were female (46.1%) and 100,282 were male (53.9%). The proportion of women diagnosed with colon cancer decreased from 2000 to 2016 (f: 26.6 to 40.1%; m: 24.9 to 41.9%; p < 0.001), and the proportion of very old patients was especially high in women (f: 27.3%; m: 15.6%; p < 0.001). The localization in women was more right-sided (f: 45.0%, m: 36.7%; p < 0.001), and women had a higher tumor grading and a higher UICC stage (especially stage III nodal-positive) at diagnosis of primary colon cancer (UICC III: f: 22.7%, m: 21.0%; p < 0.001). We could detect a significantly better overall (hazard ratio: 0.853, lower 95%: 0.841, upper 95%: 0.864; p < 0.001) and recurrence-free survival (hazard ratio: 0.857, lower 95%: 0.845, upper 95%: 0.868; p < 0.001) in women compared with men, even though women received chemotherapy less frequently compared with men (f: 26.1%, m: 28.1%; p < 0.001).

We could detect several variables that differed significantly between men and women regarding clinical, histopathological, therapeutic, and outcome factors. We believe that it is crucial to consider gender as a key factor in the diagnosis and treatment of colon cancer. Sex-specific diagnostic tools could lead to an earlier diagnosis of colon cancer in women, and ways to increase the rate of chemotherapy in women should be evaluated. Furthermore, we recommend stratifying randomized trials by gender.

The online version of this article (10.1007/s00423-019-01850-6) contains supplementary material, which is available to authorized users.

• Colon cancer
• Gender
• Sex differences

• Gender
• Personalised medicine
• Radiotherapy
• Sex
• Treatment outcome

Sex dimorphism in cell response to stress has previously been investigated by different research groups. This dimorphism could be at least in part accounted for by sex-biased expression of regulatory elements such as microRNAs (miRs). In order to spot previously unknown miR expression differences we took advantage of prior knowledge on specialized databases to identify X chromosome-encoded miRs potentially escaping X chromosome inactivation (XCI). MiR-548am-5p emerged as potentially XCI escaper and was experimentally verified to be significantly up-regulated in human XX primary dermal fibroblasts (DFs) compared to XY ones. Accordingly, miR-548am-5p target mRNAs, e.g. the transcript for Bax, was differently modulated in XX and XY DFs. Functional analyses indicated that XY DFs were more prone to mitochondria-mediated apoptosis than XX ones. Experimentally induced overexpression of miR548am-5p in XY cells by lentivirus vector transduction decreased apoptosis susceptibility, whereas its down-regulation in XX cells enhanced apoptosis susceptibility. These data indicate that this approach could be used to identify previously unreported sex-biased differences in miR expression and that a miR identified with this approach, miR548am-5p, can account for sex-dependent differences observed in the susceptibility to mitochondrial apoptosis of human DFs.

Substance abuse and depression are common psychiatric disorders with a high rate of comorbidity. Both conditions affect differently men and women and preclinical research has showed many sex differences in drug addiction and depression. The most common approach for modeling depression-addiction comorbidity is the combination of the intravenous drug self-administration and the olfactory bulbectomy (OBX) models in rats. Such a combination has revealed enhanced drug-taking and drug-seeking behaviors in OBX rats, but no study has investigated so far potential sex differences in operant responding and motivation for natural reinforcers in OBX rats. This study investigated for the first time operant self-administration of palatable food pellets in male and female OBX rats under different feeding status, i.e., ad libitum vs. restricted food, and schedules of reinforcement, i.e., a continuous ratio schedule fixed ratio 1 (FR1) vs. a complex (FR5_(x)) second order schedule of reinforcement. In the FR1 experiment, OBX rats of both sexes exhibited lower operant responding and intake of palatable food pellets than sham-operated controls, with food restriction leading to increased operant responding in both OBX and SHAM groups. Female rats showed higher responding than males but this effect was abolished by the OBX lesion. Similarly, in the (FR5_(x)) second order schedule of reinforcement both male and female OBX rats showed lower responding and food intake, with SHAM and OBX females showing higher operant responding than corresponding male groups. Overall, our findings showed that: (i) responding for food was lower in OBX than in SHAM rats under both FR1 and (FR5_(x)) schedules of reinforcement; (ii) sex and food restriction affect operant responding for palatable food; and (iii) the suppressing effect of OBX lesion on food intake was consistently present in both sexes and represents the most robust factor in the analysis. This may represent anhedonia which is associated with depressive-like phenotype and palatable food self-administration may serve as a robust behavioral index of anhedonia in the OBX model.

• depression
• food intake
• olfactory bulbectomy
• reward
• self-administration
• sex difference

Although most melanoma cases may be treated by surgical intervention upon early diagnosis, a significant portion of patients can still be refractory, presenting low survival rates within 5 years after the discovery of the illness. As a hallmark, melanomas are highly prone to evolve into metastatic sites. Moreover, melanoma tumors are highly resistant to most available drug therapies and their incidence have increased over the years, therefore leading to public health concerns about the development of novel therapies. Therefore, researches are getting deeper in unveiling the mechanisms by which melanoma initiation can be triggered and sustained. In this context, important progress has been achieved regarding the roles and the impact of cellular signaling pathways in melanoma. This knowledge has provided tools for the development of therapies based on the intervention of signal(s) promoted by these cascades. In this review, we summarize the importance of major signaling pathways (mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K)-Akt, Wnt, nuclear factor κ-light-chain-enhancer of activated B cell (NF-κB), Janus kinase (JAK)-signal transducer and activator of transcription (STAT), transforming growth factor β (TGF-β) and Notch) in skin homeostasis and melanoma progression. Available and developing melanoma therapies interfering with these signaling cascades are further discussed.

• intracellular signaling
• melanoma
• melanomagenesis
• skin cancer

• Adult
• Aged
• Biomarkers/metabolism
• Female
• Healthy Volunteers
• Humans
• Male
• Metabolomics/methods
• Middle Aged
• Sex Characteristics
• Urinary Tract/metabolism

• UL1 TR001881 NCATS NIH HHS
• U24 DK097154 NIDDK NIH HHS
• W81XWH-15-1-0415 U.S. Department of Defense (DOD)
• UL1 TR000124 NCATS NIH HHS
• Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)

A potentially illuminating way of looking at gender differences in health and disease is to study differences in drug utilization. The aim of this study was to describe gender differences in dispensed analgesics (including nonsteroidal anti-inflammatory drugs [NSAIDs]) in Sweden during 2006–2015.

The Swedish Board of Health and Welfare holds an open, Anatomical Therapeutic Chemical (ATC)–based statistical database containing aggregated data on all dispensed prescription drugs in Swedish pharmacies since 2006. The database is searchable according to sex, age (5-year intervals), and Swedish regions.

Nationwide, whole-population information was retrieved for all ATC codes at the second level for individuals ≥20 years of age, focusing on sex-related differences. More in-depth analyses were made for analgesics, including NSAIDs. Descriptive statistics were used. Gender differences in drug prescription are pervasive in Sweden; the yearly prevalence in 2015 was higher in women for 72 out of 84 ATC groups (not adjusted for age). Analgesics, including NSAIDs, were more commonly used by women in all age groups. Gender differences were sustained over time (2006–2015) and were particularly striking for triptans. For both men and women, the yearly prevalence of opioids was stable during 2006–2015, whereas it increased for paracetamol and decreased for NSAIDs. The increase in paracetamol prescription was most noticeable for young females, and the decrease in NSAID prescription was largest in older patients (irrespective of sex).

Gender differences in the use of analgesics probably mirror the higher prevalence of chronic pain in women.

• NSAIDs
• acetaminophen
• drugs
• medicines
• nonsteroidal anti-inflammatory drugs
• opioids
• paracetamol
• sex
• triptans