Sex Bias Research Articles

Co-designing formal health professions curriculum in partnership with students: A scoping review

There is growing evidence of the value of co-design and partnering with students in the design, development, and delivery of health professions education (HPE). However, the way in which students participate in co-designing HPE remains largely unexplored and there is little guidance on how to embed and strengthen partnerships with students. Using scoping review methodology, we identified and aggregated research reporting studies in which students were active partners in co-designing formal curricula in HPE. After searching five databases and screening 12,656 articles against inclusion criteria, 21 studies were identified. We found that most of the research was based in medical programs (n = 15) across Western contexts. Studies were mostly descriptive case reports (n = 10), with only three studies utilising participatory/action research designs. The co-designed outputs were mostly classroom-based learning on challenging HPE topics, for example, ethics, health inequities, racial and sexual bias, global health, and Indigenous health. Detailed descriptions of student-faculty partnerships and underpinning approaches were lacking overall. To optimise co-design methods, HPE and research require deeper engagement with critical research and pedagogical approaches and more robust evaluations of the processes, outputs and outcomes of co-design. In pedagogical practices, this necessitates challenging institutional structures, teaching and learning cultures and relational elements, such as through creating formal roles and opportunities for students as active co-design partners and fostering more equitable student-faculty positioning in HPE.

Validation and recalibration of sex estimation methods using pubic nonmetric traits for the Chilean population.

Chile had a violent military coup (1973-1990) that resulted in 3,000 victims declared detained, missing or killed; many are still missing and unidentified. Currently, the Human Rights Unit of the Forensic Medical Service in Chile applies globally recognised forensic anthropological approaches, but many of these methods have not been validated in a Chilean sample. As current research has demonstrated population-specificity with extant methods, the present study aims to validate sex estimation methods in a Chilean population and thereafter establish population-specific equations. A sample of 265 os coxae of known age and sex of adult Chileans from the Santiago Subactual Osteology Collection were analysed. Visual assessment and scoring of the pelvic traits were performed in accordance with the Phenice (1969) and Klales et al. (2012) methods. The accuracy of Phenice (1969) in the Chilean sample was 96.98%, with a sex bias of 7.68%. Klales et al. (2012) achieved 87.17% accuracy with a sex bias of -15.39%. Although both methods showed acceptable classification accuracy, the associated sex bias values are unacceptable in forensic practice. Therefore, six univariate and eight multivariate predictive models were formulated for the Chilean population. The most accurate univariate model was the ventral arc at 96.6%, with a sex bias of 5.2%. Classification accuracy using all traits was 97.0%, with a sex bias of 7.7%. This study provides Chilean practitioners a population-specific morphoscopic standard with associated classification probabilities acceptable to accomplish legal admissibility requirements in human rights and criminal cases specific to the second half of the 20th century.

Opinion: How does XIST promote sex bias in autoimmune diseases?

Opinion: How does XIST promote sex bias in autoimmune diseases?

Age and sex effects on paired-pulse suppression and prepulse inhibition of auditory evoked potentials

Responses to a sensory stimulus are inhibited by a preceding stimulus; if the two stimuli are identical, paired-pulse suppression (PPS) occurs; if the preceding stimulus is too weak to reliably elicit the target response, prepulse inhibition (PPI) occurs. PPS and PPI represent excitability changes in neural circuits induced by the first stimulus, but involve different mechanisms and are impaired in different diseases, e.g., impaired PPS in schizophrenia and Alzheimer’s disease and impaired PPI in schizophrenia and movement disorders. Therefore, these measures provide information on several inhibitory mechanisms that may have roles in clinical conditions. In the present study, PPS and PPI of the auditory change-related cortical response were examined to establish normative data on healthy subjects (35 females and 32 males, aged 19–70 years). We also investigated the effects of age and sex on PPS and PPI to clarify whether these variables need to be considered as biases. The test response was elicited by an abrupt increase in sound pressure in a continuous sound and was recorded by electroencephalography. In the PPS experiment, the two change stimuli to elicit the cortical response were a 15-dB increase from the background of 65 dB separated by 600 ms. In the PPI experiment, the prepulse and test stimuli were 2- and 10-dB increases, respectively, with an interval of 50 ms. The results obtained showed that sex exerted similar effects on the two measures, with females having stronger test responses and weaker inhibition. On the other hand, age exerted different effects: aging correlated with stronger test responses and weaker inhibition in the PPS experiment, but had no effects in the PPI experiment. The present results suggest age and sex biases in addition to normative data on PPS and PPI of auditory change-related potentials. PPS and PPI, as well as other similar paradigms, such as P50 gating, may have different and common mechanisms. Collectively, they may provide insights into the pathophysiologies of diseases with impaired inhibitory function.

Hallmarks of sex bias in immuno-oncology: mechanisms and therapeutic implications.

Sex differences are present across multiple non-reproductive organ cancers, with male individuals generally experiencing higher incidence of cancer with poorer outcomes. Although some mechanisms underlying these differences are emerging, the immunological basis is not well understood. Observations from clinical trials also suggest a sex bias in conventional immunotherapies with male individuals experiencing a more favourable response and female individuals experiencing more severe adverse events to immune checkpoint blockade. In this Perspective article, we summarize the major biological hallmarks underlying sex bias in immuno-oncology. We focus on signalling from sex hormones and chromosome-encoded gene products, along with sex hormone-independent and chromosome-independent epigenetic mechanisms in tumour and immune cells such as myeloid cells and T cells. Finally, we highlight opportunities for future studies on sex differences that integrate sex hormones and chromosomes and other emerging cancer hallmarks such as ageing and the microbiome to provide a more comprehensive view of how sex differences underlie the response in cancer that can be leveraged for more effective immuno-oncology approaches.

Preliminary Danish Norms for the Odense Child Trauma Screening (OCTS)

AbstractThe Odense Child Trauma Screening (OCTS) is Danish story stem screening tool applicable for assessment of preschoolers and young children in risk of being traumatized. Having shown initial evidence of validation, Danish norms are needed to strengthen the clinical assessment with the OCTS by serving as a baseline comparison for assessment of potentially traumatized children. We tested 169 children from the Danish general population aged 4–8 with the OCTS and investigated sex and age differences in play-based behavior and narrative representations. Caregivers reported electronically on child demographic information, psychosocial functioning, and history of trauma exposure using The Strengths and Difficulties Questionnaire (SDQ) and The Diagnostic Infant and Preschool Assessment (DIPA) trauma list. Across the 145 scores of the OCTS coding scheme, significant sex and age differences were only found in five and sixteen scores respectively. In the five codes where significant sex differences were observed, boys’ normative scores were higher. No significant sex differences were found in the partial story scores or the OCTS total score. Three significant age differences in partial story and OCTS total scores emerged with 4-year-olds scoring higher than 6–8-year-olds. We further found 13 significant age differences in code scores with higher scores among the youngest of the two groups in question suggesting that scores tend to decrease along older age. Few significant sex and age differences were found in children’s OCTS play-based behavior and narrative representations. Indicative of few sex and age biases of the OCTS coding scheme and stories, results suggest that the OCTS can be applied across the intended target group of children aged 4 to 8 years. As higher scores were found in the younger age groups, clinicians should be attentive to age in certain codes of the OCTS coding scheme in their assessment of children in clinical practice. The preliminary normative scores must be interpreted and clinically applied with caution due to our non-representative sample and lack of analyses on factors potentially influencing children’s responses to the OCTS (e.g., developmental, contextual, cultural factors).

The interplay between X-chromosome functional dosage and circadian regulation in females.

Biological factors and mechanisms that drive higher prevalence of insomnia in females are poorlyunderstood. This study focused on the neurological consequences of X-chromosome functional imbalancesbetween sexes. Benefited from publicly available large-scale genetic, transcriptional and epigenomic data, we curated andcontrasted different gene lists: (1) X-liked genes, including assignments for X-chromosome inactivation patterns anddisease associations; (2) sleep-associated genes; (3) gene expression markers for the suprachiasmatic nucleus. We show that X-linked markers for the suprachiasmatic nucleus are significantly enriched for clinicallyrelevant genes in the context of rare genetic syndromes and brain waves modulation. Considering female-specific patterns on brain transcriptional programs becomes essential whendesigning health care strategies for mental and sleep illnesses with sex bias in prevalence.

Ongoing effects of preterm birth on the dopaminergic and noradrenergic pathways in the frontal cortex and hippocampus of guinea pigs.

Children born preterm have an increased likelihood of developing neurobehavioral disorders such as attention-deficit hyperactivity disorder (ADHD) and anxiety. These disorders have a sex bias, with males having a higher incidence of ADHD, whereas anxiety disorder tends to be more prevalent in females. Both disorders are underpinned by imbalances to key neurotransmitter systems, with dopamine and noradrenaline in particular having major roles in attention regulation and stress modulation. Preterm birth disturbances to neurodevelopment may affect this neurotransmission in a sexually dimorphic manner. Time-mated guinea pig dams were allocated to deliver by preterm induction of labor (gestational age 62 [GA62]) or spontaneously at term (GA69). The resultant offspring were randomized to endpoints as neonates (24h after term-equivalence age) or juveniles (corrected postnatal day 40, childhood equivalence). Relative mRNA expressions of key dopamine and noradrenaline pathway genes were examined in the frontal cortex and hippocampus and quantified with real-time PCR. Myelin basic protein and neuronal nuclei immunostaining were performed to characterize the impact of preterm birth. Within the frontal cortex, there were persisting reductions in the expression of dopaminergic pathway components that occurred in preterm males only. Conversely, preterm-born females had increased expression of key noradrenergic receptors and a reduction of the noradrenergic transporter within the hippocampus. This study demonstrated that preterm birth results in major changes in dopaminergic and noradrenergic receptor, transporter, and synthesis enzyme gene expression in a sex- and region-based manner that may contribute to the sex differences in susceptibility to neurobehavioral disorders. These findings highlight the need for the development of sex-based treatments for improving these conditions.

Do sexes differ in consistent individual differences and behavioural syndrome in an aposematic poison frog?

AbstractThere is a burgeoning interest in studying consistent individual differences in animal behaviour. Most studies consider mainly males, but sexes are subject to distinct selection pressures that may drive differences in life history and therefore lead to differences in a variety of behaviours. Here, we used Oophaga pumilio, a poison frog with sex differences in life‐history strategies (e.g., sex bias in space use and parental care), to explore whether sexes differ or share personality characteristics like behavioural consistency and behavioural syndromes. Based on the natural history of this species, we predicted sex differences in behavioural consistency in exploration but not in boldness, and a correlation between these behavioural traits. We found no sex differences in behavioural consistency in boldness and exploration, although, we observed a tendency of higher consistency in males than females in boldness. When pooling all individuals, we found a higher consistency in boldness than exploration, suggesting the presence of a bold personality in general. We observed a positive between‐individual correlation of boldness and exploration in both sexes indicating the presence of a behavioural syndrome. Our data suggest that selective mechanisms shaping individual behaviour act equally on both sexes in this poison frog.

Abstract 3490: Unveiling sex differences in lung adenocarcinoma through multi-omics integrative protein signaling networks

Abstract Sex differences in lung adenocarcinoma (LUAD) are evident in incidence rates, prognostic outcomes, and therapy responses, yet the underlying molecular mechanisms driving these disparities remain underexplored. In this study, we conducted a comprehensive proteogenomic analysis encompassing 38 females and 73 males with LUAD from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) dataset. Employing Transcription Inference using Gene Expression and Regulatory data (TIGER), we inferred sex-differentially activated transcription factors (TFs) from The Cancer Genome Atlas (TCGA) LUAD gene expression data and identified sex-differentially activated kinases using CPTAC protein phosphorylation data. We further constructed a comprehensive kinase-TF signaling network by integrating these sex-differentially activated kinases with TFs, identifying all paths shorter than 3 in the protein interaction networks to highlight druggable pathways. Our analyses revealed that many proteins exhibit not only sex-biased abundance but also sex-biased phosphorylation and acetylation. Furthermore, these sex-biased proteins were associated with critical biological pathways including cell proliferation, immune response, and metabolism. Using kinase-TF signaling networks, we found substantial sex bias in the activities of clinically actionable TFs and kinases, including the glucocorticoid receptor (NR3C1), AR, AURKA, CDK6, and MAPK14. Leveraging the PRISM cancer cell line screening database, we identified several small-molecule drugs, such as glucocorticoid receptor agonists and aurora kinase inhibitors, potentially exhibiting sex-specific efficacy as LUAD therapeutics. Our findings showed that the activity of some clinically relevant TFs and kinases differ by sex in LUAD, underscoring the need to consider sex as a biological variable and the utility of multi-omics integrative protein signaling networks in advancing our understanding of cancer biology and the development of sex-aware therapeutics. Citation Format: Chen Chen, Enakshi Saha, Dawn L. DeMeo, John Quackenbush, Camila M. Lopes-Ramos. Unveiling sex differences in lung adenocarcinoma through multi-omics integrative protein signaling networks [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 3490.

Abstract 144: Sex bias in neuroblastoma: Worse outcomes for female patients are associated with dysregulation of DLK1 and H19

Abstract Neuroblastoma (NB) is a devastating neural crest-derived tumor primarily affects children under five. Forty percent of NB patients are classified as high-risk (HR), and less than half of them survive. HR disease is split into two equally sized groups: one exhibiting genetic amplification of the MYCN proto-oncogene (MA), and another where MYCN is non-amplified (MNon). Overall survival (OS) studies are often either poorly annotated or focused on outcomes across the entire patient group, which may mask differential outcomes or biases among NB subgroups. Here we report our assessment of OS among several genetic, histopathological, and sex-based subgroups in three different well annotated NB patient datasets. Our analysis reveals a previously unseen sex-bias in HR MNon patients, where female patients have significantly worse OS than males. This disparity carries into stage 4s NB, defined by high survival in infants despite the presence of broadly disseminated disease. In stage 4s patients across two studies, we observe no deaths among males (n=66) and 6 among females (n=48), again marking significantly worse OS in females. Expression analysis comparing male and female HR MNon patients identifies DLK1 and H19, two imprinted genes implicated in multiple malignancies, as frequently overexpressed in females. A similar pattern is seen in RNA seq analysis of human MA (n=4) and MNon (n=4) cell lines. In addition, both DLK1 and H19 are associated with worse prognosis in female but not male patients. We also report that depletion of either gene results in reduced growth in vitro. Moreover, the NB-related ATRX tumor suppressor has been shown to inhibit H19 via insertion of histone variant H3.3. We observe an inverse correlation between H3.3B and H19 expression in female HR MNon patients. Further, H19 levels increase upon ATRX depletion in human NB cells, suggesting that ATRX indeed regulates H19 in NB. These findings provide the first evidence of female-biased outcomes in NB and suggest functional involvement of DLK1, H19 and ATRX. Citation Format: Mariya Raleigh, Vishwa Patel, Lorraine R. Benhamou, Xin Shen, Dennis A. Sheeter, Erika C. Espinosa, Niharika Reddy Badi, Chase Calvert, Garrett Bourne, John T. Powers. Sex bias in neuroblastoma: Worse outcomes for female patients are associated with dysregulation of DLK1 and H19 [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 144.

Developing deep learning-based strategies to predict the risk of hepatocellular carcinoma among patients with nonalcoholic fatty liver disease from electronic health records

ObjectiveThe accuracy of deep learning models for many disease prediction problems is affected by time-varying covariates, rare incidence, covariate imbalance and delayed diagnosis when using structured electronic health records data. The situation is further exasperated when predicting the risk of one disease on condition of another disease, such as the hepatocellular carcinoma risk among patients with nonalcoholic fatty liver disease due to slow, chronic progression, the scarce of data with both disease conditions and the sex bias of the diseases. The goal of this study is to investigate the extent to which the aforementioned issues influence deep learning performance, and then devised strategies to tackle these challenges. These strategies were applied to improve hepatocellular carcinoma risk prediction among patients with nonalcoholic fatty liver disease. MethodsWe evaluated two representative deep learning models in the task of predicting the occurrence of hepatocellular carcinoma in a cohort of patients with nonalcoholic fatty liver disease (n = 220,838) from a national EHR database. The disease prediction task was carefully formulated as a classification problem while taking censorship and the length of follow-up into consideration. ResultsWe developed a novel backward masking scheme to deal with the issue of delayed diagnosis which is very common in EHR data analysis and evaluate how the length of longitudinal information after the index date affects disease prediction. We observed that modeling time-varying covariates improved the performance of the algorithms and transfer learning mitigated reduced performance caused by the lack of data. In addition, covariate imbalance, such as sex bias in data impaired performance. Deep learning models trained on one sex and evaluated in the other sex showed reduced performance, indicating the importance of assessing covariate imbalance while preparing data for model training. ConclusionsThe strategies developed in this work can significantly improve the performance of hepatocellular carcinoma risk prediction among patients with nonalcoholic fatty liver disease. Furthermore, our novel strategies can be generalized to apply to other disease risk predictions using structured electronic health records, especially for disease risks on condition of another disease.

Abstract 3261: Improving targeted therapy in female patients with lung squamous cell carcinoma

Abstract Non-small cell lung cancer (NSCLC) will claim the lives of ~60,000 female patients in the US in 2023. Lung squamous cell carcinoma (LUSC) is a subtype of Non-Small Cell Lung Cancer (NSCLC) that comprises ~30% of NSCLC and is characterized by high metabolic activity. Specifically, LUSC typically exhibits elevated rates of both glucose and glutamine metabolism driven by the PI3K-AKT-mTOR and KEAP1/NRF2 pathways. Further, a paucity of identifiable genetic drivers in LUSC has resulted in a lack of effective targeted therapies for patients with this devastating disease. Despite recent advances in therapy, the 5-year survival rate for patients with advanced NSCLC is 6%, underscoring the need for better treatment options. Importantly, no significant sex bias is seen in the newly diagnosed cases of lung cancer (~50%M/~50%F) (American Cancer Society, 2023), yet there are no sex-specific therapeutic approaches in clinical use. We demonstrated that the catalytic mTOR kinase inhibitor TAK228 can be utilized to effectively treat LUSC tumors via inhibition of glycolysis, an approach that is currently being evaluated on two phase I/II clinical trials (NCT02417701, NCT04250545), launched as a direct result of our pre-clinical work. However, our pre-clinical data suggests that despite the potential benefit of TAK228 inhibition in LUSC, a subset of tumors are resistant to TAK228 despite on-target activity of mTOR inhibitor, leading to the rationale of the current hypothesis, namely the possibility that sex-specific differential effects of TAK228 may exist. To evaluate this hypothesis, we have generated preliminary data demonstrating that sex is a determinant of TAK228 response in LUSCs, whereby male mice are significantly more sensitive to mTOR inhibition than females. Follow-on experiments have demonstrated that the anti-estrogen therapy (Letrozole) sensitized previously resistant female mice bearing LUSCs to TAK228, suggesting an estrogen-related link to TAK228 resistance in females. Additionally, RNASeq and biochemical analyses identified pathways that are upregulated in TAK228 resistant female mice with LUSC tumors. These results suggest that the estrogen may play a key role in the observed pattern of female resistance to mTOR inhibition. As such, the goal of the current proposal is to evaluate the catalytic mTOR kinase inhibitor TAK228, in combination with anti-estrogen therapy as a therapeutic strategy to treat LUSC in females. Citation Format: Milica Momcilovic, David Shackelford. Improving targeted therapy in female patients with lung squamous cell carcinoma [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 3261.

Sex matters: The MouseX DW-ALLEN Atlas for mice diffusion-weighted MR imaging

Overcoming sex bias in preclinical research requires not only including animals of both sexes in the experiments, but also developing proper tools to handle such data. Recent work revealed sensitivity of diffusion-weighted MRI to glia morphological changes in response to inflammatory stimuli, opening up exciting possibilities to characterize inflammation in a variety of preclinical models of pathologies, the great majority of them available in mice. However, there are limited resources dedicated to mouse imaging, like those required for the data processing and analysis. To fill this gap, we build a mouse MRI template of both structural and diffusion contrasts, with anatomical annotation according to the Allen Mouse Brain Atlas, the most detailed public resource for mouse brain investigation. To achieve a standardized resource, we use a large cohort of animals in vivo, and include animals of both sexes. To prove the utility of this resource to integrate imaging and molecular data, we demonstrate significant association between the mean diffusivity from MRI and gene expression-based glia density. To demonstrate the need of equitable sex representation, we compared across sexes the warp fields needed to match a male-based template, and our template built with both sexes. Then, we use both templates for analysing mice imaging data obtained in animals of different ages, demonstrating that using a male-based template creates spurious significant sex effects, not present otherwise. All in all, our MouseX DW-ALLEN Atlas will be a widely useful resource getting us one step closer to equitable healthcare.

Sex reporting of cells used in cancer research: A systematic review.

Sex and gender disparities in biomedical research have been emphasized to improve scientific knowledge applied for the health of both men and women. Despite sex differences in cancer incidence, prognosis, and responses to therapeutic agents, mechanistic explanations at molecular levels are far from enough. Recent studies suggested that cell sex is an important biological variable due to differences in sex chromosome gene expression and differences in events associated with developmental biology. The objective of this study was to analyze the reporting of sex of cells used in cancer research using articles published in Cancer Cell, Molecular Cancer, Journal of Hematology & Oncology, Journal for ImmunoTherapy of Cancer, and Cancer Research in 2020, and to examine whether there exists any sex bias. We found that the percentage of cells with sex notation in the article was 36.5%. Primary cells exhibited higher sex notation compared to cell lines. A higher percentage of female cells were used in cell cultures with sex notation. Also, sex-common cells omitted sex description more often compared to sex-specific cells. None of the cells isolated from embryo and esophagus reported the cell sex in the article. Our results indicate cell sex report in cancer research is limited to a small proportion of cells used in the study. These results call for acknowledging the sex of cells to increase the applicability of biomedical research discoveries.

Differential Regulation of Immune-Related Genes in the Developing Heart.

In many congenital heart defects, it can be difficult to ascertain primary pathology from secondary consequences from altered flow through the developing heart. The molecular differences between the growing right and left ventricles (RV and LV, respectively) following the completion of septation and the impact of sex on these mechanisms have not been investigated.We analyzed RNA-seq data derived from twelve RV and LVs, one with Hypoplastic Left Heart Syndrome (HLHS), to compare the transcriptomic landscape between the ventricles during development. Differential gene expression analysis revealed a large proportion of genes unique to either the RV or LV as well as sex bias. Our GO enrichment and network analysis strategy highlighted the differential role of immune functions between the RV and LV in the developing heart. Comparatively, RNA-seq analysis of data from C57Bl6/J mice hearts collected at E14 resulted in the enrichment of similar processes related to T cells and leukocyte migration and activation. Differential gene expression analysis of an HLHS case highlighted significant downregulation of chromatin organization pathways and upregulation of genes involved in muscle organ development. This analysis also identified previously unreported upregulation of genes involved in IL-17 production pathways. In conclusion, differences exist between the gene expression profiles of RV versus LV with the expression of immune-related genes beingsignificantly different between these two chambers. The pathogenesis of HLHS may involve alterations in the expression of chromatin and muscle gene organization as well as upregulation of the IL-17 response pathway.

Sex differences on constitutive long non-coding RNA expression: Modulatory effect of estradiol and testosterone in muscle cells.

Despite the growing awareness of sexual dimorphism between males and females under pathological and physiological conditions, sex bias in biomedical research in animal models and patients is still present nowadays. The main objective of this work was to investigate sex differences in constitutive long non-coding RNA expression in spinal cord and skeletal muscle from wild-type mice. To assess the influence of gender on long non-coding RNAs, we extracted RNA from tissues of male and female mice and analyzed the expression on nine long non-coding RNAs, selected for being among the most commonly studied or exerting an important role in muscle, at 50, 60, and 120 days of age. We observed age- and tissue-dependent significant sex differences, being more prominent in skeletal muscle. We also studied the effect of sex steroid hormones on long non-coding RNA expression in vitro, noticing a modulation of long non-coding RNA levels upon estradiol and dihydrotestosterone treatment in muscle. Taken together, results obtained evidenced sex differences on constitutive long non-coding RNA expression and suggested an influence of steroid hormones complementary to other possible factors. These findings emphasize the importance of including both sexes in experimental design to minimize any potential sex bias.

Artificial intelligence based prediction model of in-hospital mortality among females with acute coronary syndrome: for the Jerusalem Platelets Thrombosis and Intervention in Cardiology (JUPITER-12) Study Group.

Despite ongoing efforts to minimize sex bias in diagnosis and treatment of acute coronary syndrome (ACS), data still shows outcomes differences between sexes including higher risk of all-cause mortality rate among females. Hence, the aim of the current study was to examine sex differences in ACS in-hospital mortality, and to implement artificial intelligence (AI) models for prediction of in-hospital mortality among females with ACS. All ACS patients admitted to a tertiary care center intensive cardiac care unit (ICCU) between July 2019 and July 2023 were prospectively enrolled. The primary outcome was in-hospital mortality. Three prediction algorithms, including gradient boosting classifier (GBC) random forest classifier (RFC), and logistic regression (LR) were used to develop and validate prediction models for in-hospital mortality among females with ACS, using only available features at presentation. A total of 2,346 ACS patients with a median age of 64 (IQR: 56-74) were included. Of them, 453 (19.3%) were female. Female patients had higher prevalence of NSTEMI (49.2% vs. 39.8%, p < 0.001), less urgent PCI (<2 h) rates (40.2% vs. 50.6%, p < 0.001), and more complications during admission (17.7% vs. 12.3%, p = 0.01). In-hospital mortality occurred in 58 (2.5%) patients [21/453 (5%) females vs. 37/1,893 (2%) males, HR = 2.28, 95% CI: 1.33-3.91, p = 0.003]. GBC algorithm outscored the RFC and LR models, with area under receiver operating characteristic curve (AUROC) of 0.91 with proposed working point of 83.3% sensitivity and 82.4% specificity, and area under precision recall curve (AUPRC) of 0.92. Analysis of feature importance indicated that older age, STEMI, and inflammatory markers were the most important contributing variables. Mortality and complications rates among females with ACS are significantly higher than in males. Machine learning algorithms for prediction of ACS outcomes among females can be used to help mitigate sex bias.

Poor rhinitis and asthma control is associated with decreased health-related quality-of-life and utilities: A MASK-air study

BackgroundAllergic rhinitis (AR) and asthma may impact health-related quality-of-life. However, national estimates on the quality-of-life of patients with AR or asthma are lacking. ObjectiveTo provide estimates for utility scores and EQ-5D Visual Analog Scale (VAS) for patients with AR or asthma. MethodsWe conducted a cross-sectional study using direct patient data from the MASK-air® app on European MASK-air® users with self-reported AR or asthma. We used a multiattribute instrument (EQ-5D) to measure quality-of-life (as utility scores and EQ-5D VAS values). Mean scores were calculated per country and disease control level using multilevel regression models with post-stratification, accounting for age and sex biases. ResultsWe assessed data from up to 7905 MASK-air® users reporting a total of up to 82,737 days. For AR, utilities ranged from 0.86-0.99 for good control versus 0.72-0.85 for poor control; EQ-5D VAS levels ranged from 78.9-87.9 for good control versus 55.3-64.2 for poor control. For asthma, utilities ranged from 0.84-0.97 for good control versus 0.73-0.87 for poor control; EQ-5D VAS levels ranged from 68.4-81.5 for good control versus 51.4-64.2 for poor control. Poor disease control was associated with a mean loss of 0.14 utilities for both AR and asthma. For the same control levels, AR and asthma were associated with similar utilities and EQ-5D VAS levels. However, lower values were observed for asthma+AR when compared to AR alone. ConclusionPoor AR or asthma control are associated with reduced quality-of-life. The estimates obtained from mHealth data may provide valuable insights for health technology assessment studies.

The gut microbiome modulates the susceptibility to traumatic stress in a sex-dependent manner.

Post-traumatic stress disorder (PTSD), a psychological condition triggered by exposure to extreme or chronic stressful events, exhibits a sex bias in incidence and clinical manifestations. Emerging research implicates the gut microbiome in the pathogenesis of PTSD and its roles in stress susceptibility. However, it is unclear whether differential gut microbiota contribute to PTSD susceptibility in male and female rats. Here, we utilized the single prolonged stress animal model and employed unsupervised machine learning to classify stressed animals into stress-susceptible subgroups and stress-resilient subgroups. Subsequently, using 16S V3-V4 rDNA sequencing, we investigated the differential gut microbiota alterations between susceptible and resilient individuals in male and female rats. Our findings revealed distinct changes in gut microbiota composition between the sexes at different taxonomic levels. Furthermore, the abundance of Parabacteroides was lower in rats that underwent SPS modeling compared to the control group. In addition, the abundance of Tenericutes in the stress-susceptible subgroup was higher than that in the control group and stress-resilient subgroup, suggesting that Tenericutes may be able to characterize stress susceptibility. What is particularly interesting here is that Cyanobacteria may be particularly associated with anti-anxiety effects in male rats. This study underscores sex-specific variations in gut microbiota composition in response to stress and sex differences should be taken into account when using macrobiotics for neuropsychiatric treatment, highlighting potential targets for PTSD therapeutic interventions.