A contemporary review of breast cancer risk factors and the role of artificial intelligence.

Background: Breast cancer continues to be a significant global health issue, necessitating advancements in prevention and early detection strategies. This review aims to assess and synthesize research conducted from 2020 to the present, focusing on breast cancer risk factors, including genetic, lifestyle, and environmental aspects, as well as the innovative role of artificial intelligence (AI) in prediction and diagnostics. Methods: A comprehensive literature search, covering studies from 2020 to the present, was conducted to evaluate the diversity of breast cancer risk factors and the latest advances in Artificial Intelligence (AI) in this field. The review prioritized high-quality peer-reviewed research articles and meta-analyses. Results: Our analysis reveals a complex interplay of genetic, lifestyle, and environmental risk factors for breast cancer, with significant variability across different populations. Furthermore, AI has emerged as a promising tool in enhancing the accuracy of breast cancer risk prediction and the personalization of prevention strategies. Conclusion: The review highlights the necessity for personalized breast cancer prevention and detection approaches that account for individual risk factor profiles. It underscores the potential of AI to revolutionize these strategies, offering clear recommendations for future research directions and clinical practice improvements.

Towards understanding sex differences in autism spectrum disorders.

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by social deficits, repetitive behaviours and lack of empathy. Its significant genetic heritability and potential comorbidities often lead to diagnostic and therapeutic challenges. This review addresses the biological basis of ASD, focusing on the sex differences in gene expression and hormonal influences. ASD is more commonly diagnosed in males at a ratio of 4:1, indicating a potential oversight in female-specific ASD research and a risk of underdiagnosis in females. We consider how ASD manifests differently across sexes by exploring differential gene expression in female and male brains and consider how variations in steroid hormones influence ASD characteristics. Synaptic function, including excitation/inhibition ratio imbalance, is influenced by gene mutations and this is explored as a key factor in the cognitive and behavioural manifestations of ASD. We also discuss the role of micro RNAs (miRNAs) and highlight a novel mutation in miRNA-873, which affects a suite of key synaptic genes, neurexin, neuroligin, SHANK and post-synaptic density proteins, implicated in the pathology of ASD. Our review suggests that genetic predisposition, sex differences in brain gene expression, and hormonal factors significantly contribute to the presentation, identification and severity of ASD, necessitating sex-specific considerations in diagnosis and treatments. These findings advocate for personalized interventions to improve the outcomes for individuals with ASD.

Evaluation of Hormonal Factors in Acne Vulgaris and the Course of Acne Vulgaris Treatment with Contraceptive-Based Therapies in Young Adult Women.

Acne vulgaris is a common chronic inflammatory skin disease, which is considered one of the diseases of civilization due to the significant influence of environmental factors on the severity and frequency of these lesions. The aim of this study was to evaluate the hormonal profile of patients before treatment and to assess selected hormonal parameters after treatment. Our first objective was to examine the correlation between the selected hormonal parameters and the severity of acne before treatment. Our second objective was to evaluate the impact of treatment with three therapies, as measured by the selected hormonal parameters and acne severity. Statistical calculations were performed using the R v.4.1.1 statistical calculation environment (IDE RStudio v. 1.4.1717) with a significance level for the statistical tests set at α = 0.05. The results showed that the women in the pre-treatment (T1) and control (C) groups had significant differences in testosterone, androstendione, FAI, SHBG, prolactin, ACTH, and cortisol concentrations. After treatment, there were still significant differences in testosterone, androstendione, FAI, and SHBG concentrations between the post-treatment (T2) and control groups. We concluded that testosterone, androstendione, and cortisol concentrations correlate with acne severity. Acne in adult women may be an important clinical marker of androgen excess syndrome and cannot be considered a transient symptom of puberty. The mainstay of acne treatment is contraceptive therapy (ethonylestradiol and drospirenone). In this study, we confirmed the effectiveness of three contraceptive-based treatments using hormonal parameters and acne severity.

Unexpected Motherhood-Triggered Hearing Loss in the Two-Pore Channel (TPC) Mutant Mouse.

Calcium signaling is crucial for many physiological processes and can mobilize intracellular calcium stores in response to environmental sensory stimuli. The endolysosomal two-pore channel (TPC), regulated by the second messenger nicotinic acid adenine dinucleotide phosphate (NAADP), is one of the key components in calcium signaling. However, its role in neuronal physiology remains largely unknown. Here, we investigated to what extent the acoustic thresholds differed between the WT mice and the TPC KO mice. We determined the thresholds based on the auditory brainstem responses (ABRs) at five frequencies (between 4 and 32 kHz) and found no threshold difference between the WT and KO in virgin female mice. Surprisingly, in lactating mothers (at P9-P10), the thresholds were higher from 8 to 32 kHz in the TPC KO mice compared to the WT mice. This result indicates that in the TPC KO mice, physiological events occurring during parturition altered the detection of sounds already at the brainstem level, or even earlier.

Reproductive and external hormonal factors and the risk of renal cell cancer in the Netherlands Cohort Study.

BACKGROUND: Several reproductive and hormonal factors, like age at menarche, parity, age at menopause, use of oral contraceptives and postmenopausal treatment, have been associated with the risk of renal cell cancer (RCC) in women, but results have not always been consistent. We therefore investigated the association between these factors and the risk of RCC in postmenopausal women participating in the Netherlands Cohort Study on Diet and Cancer. METHODS: Information on reproductive history, exogenous hormone use and gynecological surgery was obtained through a self-administered questionnaire at baseline in 1986. After 20.3 years of follow-up, 204 cases and 2280 subcohort members were available for case-cohort analysis. Multivariable hazard ratios (HR) were calculated using Cox Proportional Hazard analysis. RESULTS: Women who reported a hysterectomy had an increased RCC risk compared to women who did not (HR, 1.42, 95%CI, 1.01-2.00). Women with a natural age at menopause between 45 and 49 years compared to 50-54 years had an increased RCC risk (HR, 1.61; 95%CI, 1.10-2.35). RCC risk was slightly and not statistically significant increased among parous women with three or more children and age at first birth before 25 years compared to nulliparous women (HR, 1.36; 95% confidence interval (CI), 0.84-2.20). No associations were observed with RCC risk for age at menarche, use of oral contraceptives and use of hormonal replacement therapy. CONCLUSION: Hysterectomy and age at natural menopause were associated with an increased RCC risk. Other hormonal and reproductive factors and RCC risk were not increased. Further studies are required to establish the mechanism(s) that explain the observed association.

Hormonal and Reproductive Factors in Relation to Cardiovascular Events in Women with Early Rheumatoid Arthritis.

Hormonal and reproductive factors affect the risk for cardiovascular events (CVE) in the general population. Although the risk of CVE is increased in rheumatoid arthritis (RA), the knowledge about the impact of hormonal factors for CVE in RA is sparse. Female postmenopausal patients ≤80 years with early RA were consecutively included in this observational study (n = 803) between 1 January 1996 until 31 December 2017. Questionnaires regarding hormonal factors were distributed from the index date. Data regarding CVE were obtained from the Swedish National Health Register and Cause of Death Register. Associations between CVE and hormonal factors were analyzed using Cox proportional hazard regression. Of the postmenopausal women, 64 women had a CVE after RA onset. The time period from menopause to RA onset was significantly longer for CVE cases with higher proportion of postmenopausal women. In Cox proportional hazard regression models, years from last childbirth and multiparity were associated with higher CVE risk. Adjustments for traditional risk factors did not affect the results except for hypertension. RA onset after menopause and a longer duration from menopause until onset increased the CVE risk. Multiparity was associated with higher CVE risk whilst oral contraceptives decreased the risk. These results can contribute to identification of high-risk patients for CVE beyond traditional risk factors.

Women and Lung Cancer.

The world is witnessing a global epidemic of lung cancer in women. Cigarette smoking remains the dominant risk factor in both sexes, but multiple observations suggest that important sex-related distinctions in lung cancer exist. These include differences in histologic distribution, prevalence in never-smokers, frequency of activating EGFR mutations, likelihood of DNA adduct accumulation, and survival outcomes. Important questions such as whether women are more susceptible to carcinogenic effects of smoking or derive more benefit from lung cancer screening merit more study. A deeper understanding of sex-related differences in lung cancer may lead to improved outcomes for both women and men.

Somatic profile in lung cancers is associated to reproductive factors in never-smokers women: Results from the IFCT-1002 BioCAST study.

BACKGROUND: Lung cancer in women is on the rise, with a higher proportion occurring in lifelong never-smokers. Lung cancer in never-smokers (LCINS) exhibits a high frequency of driver oncogene alterations. In this study, we aimed to investigate whether exposure to reproductive factors in women with LCINS may modulate the molecular pattern. METHODS: All newly diagnosed LCINSs were included in a prospective, observational study (IFCT-1002 BioCAST). Each patient responded to a questionnaire including reproductive factors. Biomarker test results were also collected. RESULTS: Two hundred and sixty women were included in this analysis, and 166 alterations were characterized. EGFR mutation frequency proved greater among patients with late menarche (74% in age>14 vs. 40% and 41% for 12-14 and ≤12 years, respectively; P=0.020) and tended to decrease with increasingly late age at menopause. In multivariate analysis, EGFR mutation frequency increased by 23% per increment of 1 year of age at menarche (P=0.048), and by 9% for each year at age at first birth (P=0.035). ALK alteration frequency was greater in women with high parity (50% in≥5 vs. 12% and 7% for 1-4 and nulliparity, respectively; P=0.021). CONCLUSION: In a cohort of women LCINSs, female hormonal factors appear to impact molecular pattern.

Lung Cancer in Women: A Modern Epidemic.

Lung cancer in women is a modern epidemic and a major health crisis. Cigarette smoking remains the most important risk factor for lung cancer, and unfortunately smoking rates are either stabilized or continue to increase among women. Women may not be more susceptible to the carcinogenic effects of tobacco, but the biology of lung cancer differs between the sexes. This paper summarizes the biological sex differences in lung cancer, including molecular abnormalities, growth factor receptors, hormonal influences, DNA repair capacity, as well as differences in the histology and treatment outcomes of lung cancer in women.

Reproductive and Hormonal Factors in Relation to Lung Cancer Among Nepali Women.

Background: Of the 1.8 million global incident lung cancer cases estimated in 2012, approximately 60% occurred in less developed regions. Prior studies suggest sex differences in lung cancer risk and a potential role for reproductive and hormonal factors in lung cancer among women. However, the majority of these studies were conducted in developed regions. No prior study has assessed these relationships among Nepali women. Methods: Using data from a hospital-based case-control study conducted in B. P. Koirala Memorial Cancer Hospital (Nepal, 2009-2012), relationships between reproductive and hormonal factors and lung cancer were examined among women aged 23-85 years. Lung cancer cases (n = 268) were frequency-matched to controls (n = 226) based on age (±5 years), ethnicity and residential area. The main exposures in this analysis included menopausal status, age at menarche, age at menopause, menstrual duration, gravidity, and age at first live-birth. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression. Results: Among postmenopausal women, those with a younger age at menopause (<45 years; 45-49 years) had an increased odds of lung cancer compared to those with an older (≥50 years) age at menopause [OR (95%CI): 2.14 (1.09, 4.17); OR (95% CI): 1.93 (1.07, 3.51)], after adjusting for age and cumulative active smoking years. No statistically significant associations were observed with the other reproductive and hormonal factors examined. Conclusion: These results suggest that Nepali women with prolonged exposure to endogenous ovarian hormones, via later age at menopause, may have a lower odds of lung cancer.

Analysis of 1135 gut metagenomes identifies sex-specific resistome profiles.

Several gastrointestinal diseases show a sex imbalance, although the underlying (patho)physiological mechanisms behind this are not well understood. The gut microbiome may be involved in this process, forming a complex interaction with host immune system, sex hormones, medication and other environmental factors. Here we performed sex-specific analyses of fecal microbiota composition in 1135 individuals from a population-based cohort. The overall gut microbiome composition of females and males was significantly different (p = 0.001), with females showing a greater microbial diversity (p = 0.009). After correcting for the effects of intrinsic factors, smoking, diet and medications, female hormonal factors such as the use of oral contraceptives and undergoing an ovariectomy were associated with microbial species and pathways. Females had a higher richness of antibiotic-resistance genes, with the most notable being resistance to the lincosamide nucleotidyltransferase (LNU) gene family. The higher abundance of resistance genes is consistent with the greater prescription of the Macrolide-Lincosamide-Streptogramin classes of antibiotics to females. Furthermore, we observed an increased resistance to aminoglycosides in females with self-reported irritable bowel syndrome. These results throw light upon the effects of common medications that are differentially prescribed between sexes and highlight the importance of sex-specific analysis when studying the gut microbiome and resistome.

Study of lipid metabolism by estimating the fat fraction in different breast tissues and in various breast tumor sub-types by in vivo 1H MR spectroscopy.

PURPOSE: To evaluate the utility of fat fraction (FF) for the differentiation of different breast tissues and in various breast tumor subtypes using in vivo proton (1H) magnetic resonance spectroscopy (MRS). METHODS: 1H MRS was performed on 68 malignant, 35 benign, and 30 healthy volunteers at 1.5 T. Malignant breast tissues of patients were characterized into different subtypes based on the differences in the expression of hormone receptors and the FF was calculated. Further, the sensitivity and specificity of FF to differentiate malignant from benign and from normal breast tissues of healthy volunteers was determined using receiver operator curve (ROC) analysis. RESULTS: A significantly lower FF of malignant (median 0.12; range 0.01-0.70) compared to benign lesions (median 0.28; range 0.02-0.71) and normal breast tissue of healthy volunteers (median 0.39; range 0.06-0.76) was observed. No significant difference in FF was seen between benign lesions and normal breast tissues of healthy volunteers. Sensitivity and specificity of 75% and 68.6%, respectively was obtained to differentiate malignant from benign lesions. For the differentiation of malignant from healthy breast tissues, 76% sensitivity and 74.5% specificity was achieved. Higher FF was seen in patients with ER-/PR- status as compared to ER+/PR+ patients. Similarly, FF of HER2neu+ tumors were significantly higher than in HER2neu- breast tumors. CONCLUSION: The results showed the potential of in vivo 1H MRS in providing insight into the changes in the fat content of different types of breast tissues and in various breast tumor subtypes.

Environmental factors and hormones in the development of rheumatoid arthritis.

The etiopathogenesis of rheumatoid arthritis (RA) is partially understood. Genetic, environmental, and hormonal factors and their interactions are considered to play an important role on disease development. The relative contribution of environmental factors to RA development is probably larger than previously thought. The aim of this review is to appraise robust evidence about the role of environmental and hormonal risk factors for RA. We will discuss inhaled pollutants, nutritional habits, infectious, hormonal, and reproductive factors. As some of these factors are potentially modifiable, understanding their impact on RA development opens new opportunities for potential interventions and disease prevention.

Understanding Risky Behavior: The Influence of Cognitive, Emotional and Hormonal Factors on Decision-Making under Risk.

Financial risky decisions and evaluations pervade many human everyday activities. Scientific research in such decision-making typically explores the influence of socio-economic and cognitive factors on financial behavior. However, very little research has explored the holistic influence of contextual, emotional, and hormonal factors on preferences for risk in insurance and investment behaviors. Accordingly, the goal of this review article is to address the complexity of individual risky behavior and its underlying psychological factors, as well as to critically examine current regulations on financial behavior.

The role of female hormonal factors in the development of rheumatoid arthritis.

RA is the most common chronic systemic autoimmune disease, with a higher prevalence in women, suggesting female hormonal factors play a role in the development of the disease. However, many controversies still exist. The aim of this review was to appraise data from recent research concerning female hormonal factors and their association with RA disease development. The study of female hormonal factors is challenging because serum levels may differ throughout a woman's lifetime and interact with various environmental, immunological, genetic and endocrine factors influencing the development of autoimmunity. As some female hormonal factors may be potentially modifiable, understanding their impact on RA development is clinically relevant and may result in specific preventive interventions in high-risk populations.

Voice in female-to-male transsexual persons after long-term androgen therapy.

OBJECTIVES/HYPOTHESIS: The aim of the present study was to 1) document voice in a large sample of female-to-male transsexual persons (FMT), 2) compare their vocal characteristics with those of heterosexual biological males, and 3) determine hormonal factors with impact on their fundamental frequency. STUDY DESIGN: This was a controlled cross-sectional study. It is the largest study to date on voice and voice change in FMT, and the first to include a control group and FMT who were under long-term androgen administration. METHODS: Thirty-eight FMT, ranging in age between 22 and 54 years, and 38 controls, frequency matched by age and smoking behavior, underwent a voice assessment that comprised the determination of pitch, intonation, and perturbation parameters measured during sustained vowel production, counting, and reading. Hormonal factors explored were hematocrit, total testosterone level, luteinizing hormone level, and biallelic mean length of the cytosine-adenine-guanine (CAG) trinucleotide repeat sequence in the androgen receptor gene. RESULTS: It was found that the FMT as a group did not differ significantly from controls for any of the acoustic voice variables studied. However, in about 10% pitch lowering was not totally unproblematic. The lowest-pitched (i.e., more male) voices were observed in FMT with higher hematocrit and longer CAG repeats. CONCLUSION: After long-term androgen therapy, FMT generally demonstrate an acceptable male voice. Pitch-lowering difficulties can be expected in about 10% of cases and appear, at least in part, to be associated with diminished androgen sensitivity. LEVEL OF EVIDENCE: 3b.

Ameliorated stress related proteins are associated with improved cardiac function by sarcoplasmic reticulum calcium ATPase gene transfer in heart failure.

BACKGROUND: Previous studies showed that overexpression of sarco-endoplasmic reticulum calcium ATPase (SERCA2a) in a variety of heart failure (HF) models was associated with greatly enhanced cardiac performance. However, it still undefined the effect of SERCA2a overexpression on the systemic inflammatory response and neuro-hormonal factors. METHODS: A rapid right ventricular pacing model of experimental HF was used in beagles. Then the animals underwent recombinant adeno-associated virus 1 (rAAV1) mediated gene transfection by direct intra-myocardium injection. HF animals were randomized to receive the SERCA2a gene, enhanced green fluorescent protein (control) gene, or equivalent phosphate buffered saline. Thirty days after gene delivery, the cardiac function was evaluated by echocardiographic testing. The protein level of SERCA2a was measured by western blotting. The proteomic analysis of left ventricular (LV) sample was determined using two-dimensional (2-D) gel electrophoresis and MALDI-TOF-MS. The serum levels of the systemic inflammatory and neuro-hormonal factors were assayed using radioimmunoassay kits. RESULTS: The cardiac function improved after SERCA- 2a gene transfer due to the significantly increased SERCA2a protein level. Beagles treated with SERCA2a had significantly decreased serum levels of the inflammatory markers (interleukin-6 and tumor necrosis factor-α) and neuro-hormonal factors (brain natriuretic peptide, endothelin-1 and angiotensin II) compared with HF animals. The myocardial proteomic analysis showed that haptoglobin heavy chain, heat shock protein (alpha-crystallin-related, B6) were down-regulated, and galectin-1 was up-regulated in SERCA2a group compared with HF group, companied by up-regulated contractile proteins and NADH dehydrogenase. CONCLUSIONS: These findings demonstrate that regional intramyocardial injections of rAAV1-SERCA2a vectors may improve global LV function, correlating with reverse activation of the systemic inflammatory, excessive neuroendocrine factors and the stress-associated myocardial proteins, suggesting that the beneficial effects of SERCA2a gene transfer may involve the attenuation of stress-associated reaction.

Avaliação dos fatores hormonais em mulheres com diagnóstico de neoplasia de mama com idade superior a 40 anos / Evaluation of hormonal factors in women diagnosed with breast neoplasia at age superior than 40 years

Introdução: O câncer de mama apresenta elevada incidência e mortalidade em todo o mundo, representando um grave problema de saúde pública. Ele é o segundo tipo de câncer mais frequente no mundo e o mais frequente entre as mulheres. Objetivo: Compreender como os fatores de risco hormonais podem influenciar no desenvolvimento de câncer de mama em mulheres com idade superior a 40 anos. Materiais e métodos: Estudo retrospectivo e transversal através da revisão de prontuários de pacientes com idade superior a 40 anos e portadoras de câncer de mama, atendidas no ambulatório de mastologia da Universidade do Vale do Itajaí (UNIVALI), em Itajaí (SC), de janeiro de 2003 até março de 2009; 484 pacientes foram incluídas no estudo. Foi analisada a relação de cada fator hormonal estudado em cada faixa etária. Os dados foram analisados através do teste de t e por regressão logística. Consideramos um nível de significância estatística de 0,05. Resultados: A menarca precoce confirmou-se como fator de risco para o aparecimento precoce do câncer de mama assim como o uso de contraceptivo oral hormonal, ambos com p<0,05. Ausência de aleitamento , abortamento, idade da menopausa e uso de terapia hormonal não foram fatores com significância estatística para o desenvolvimento de câncer de mama. Observou-se que o número elevado de gestações confirma-se como fator protetor. Conclusão: Uma vez que não sabemos quais os exatos fatores de risco para o desenvolvimento de neoplasia mamária, sugerimos que o screening para câncer de mama seja modificado e individualizado no sentido de intervir de maneira mais eficiente.

Background: Breast cancer presents high incidence and mortality all over the world, representing an important problem for public health. It is the second most common type of cancer in the world and the commonest malignancy in women. Objective: Understand how hormonal risk factors influence the breast cancer development in women with age higher than 40 years. Methods: retrospective and transversal study through charts review of patients aged over 40 years, diagnosed with breast cancer, in mastology service of University of Vale do Itajaí (UNIVALI), Itajaí (SC) from January 2003 until March 2009. We found 484 patients. We analized the relationship of each hormonal factor with age estratified by decades. The data were analized through t test and logistic regression. We consider a statistical significance level of 0.05. Results: Early menarche and hormonal contraceptive were confirmed as risk factors for breast cancer (p<0,05). Lack of breastfeeding, abortion, menopause age and hormonal therapy were not significanthy statistical for breast cancer diagnosis. The high number of pregnancies persists as a protective factor. Conclusions: Once we don?t know exactly wich risk factors act in the development of breast cancer, we sugest to modify and individualize the screening for breast cancer, so we can interact in a efficiently way.