Differences In Outcomes Research Articles

Differences in genomic, transcriptomic, and immune landscape of prostate cancer (PCa) based on site of metastasis (mets).

21 Background: In patients with metastatic PCa, specific sites of mets are associated with differential overall survival, with lymph node (LN) only disease having the best survival, followed by bone, lung, and liver, with each showing progressively worse survival. However, the biology of tropism to specific sites and differential outcomes has not been fully explored. Herein, utilizing a large, multi-institutional, real-world dataset, we hypothesized that differences in molecular and immune landscape of PCa based on site of mets may explain different clinical outcomes. Methods: DNA (592-gene panel or whole exome) and RNA (whole transcriptome) sequencing was performed for primary PCa (PPCa) and unpaired PCa mets sites (non-visceral: NV and visceral: V) and sequenced at Caris Life Sciences (Phoenix, AZ). Mismatch repair deficiency/microsatellite instability-high (dMMR/MSI-H) was tested by IHC/NGS, respectively. Tumor mutational burden (TMB) (high >10 mut/Mb) was assessed. Androgen receptor (AR) signaling score and Neuroendocrine Prostate Cancer (NEPC) score were calculated using previously defined RNA-based signatures. Pathway enrichment was determined by Gene Set Enrichment Analysis (GSEA). Immune cell fractions calculated by deconvolution of WTS using quanTIseq. Statistical significance was determined by chi-square and Mann-Whitney U tests. All analyses done with CODEai. Results: 6074 PCa samples, including 3411 PPCa, 1634 NV (bone = 784, LN = 850) and 1029 V (liver: 468, lung: 177, bladder: 241, other: 143) were evaluated. Age at sample collection ranged 30 to 70+ years. Compared to PPCa, significantly higher mutation rates were observed for multiple genes in V (RB1 8% vs 3%, TP53 43% vs 31%, PTEN 12 % vs 8%, CTNNB1 8% vs 3%, AR 13% vs 1%, APC 15% vs 5%, AKT1 4% vs 2%; p<0.05 for all) and NV mets (AR 9% vs 1%, SPOP 7% vs 10%, TP53 38% vs 31%, CTNNB1 6% vs 3%, and KMT2C 8 % vs 5%; p<0.05 for all). Alterations of RB1, APC and AR were more frequent, and SPOP less common in liver mets compared to PPCa, while SPOP, KRAS, PIK3CA, APC and BAP1 mutations were more common in lung mets (p < 0.05 for all). Compared to PPCa, V and NV mets had higher AR signaling and interferon-γ scores, while V mets had higher NEPC scores and were more frequently PD-L1+ (SP142) and TMB-high (p<0.05 for all). No differences in dMMR/MSI-H was observed between PPCa, V and NV mets. AR-V7 variant prevalence was significantly higher in V (36%) and NV (33%) mets compared to PPCa (7%, p-value < 0.05). GSEA identified E2F, G2M checkpoint and MYC target pathways as being more upregulated in both V and NV mets compared to PPCa (q<0.05). Compared to PPCa, V and NV mets were significantly less enriched in macrophage M2, NK cells and Tregs, while V mets were also less enriched in B cells and neutrophils (p<0.05). Conclusions: We elucidate molecular and immunologic mechanisms of metastatic tropism in advanced PCa. These data may facilitate future drug development.

Abstract TP173: Differential Outcomes and Treatment in Vertebral versus Carotid Artery Dissections: A National Inpatient Sample Study

Introduction: Cervical artery dissection (CAD) involves the carotid (CCAD) or vertebral artery (VCAD). However, limited studies have compared their clinical features and outcomes. Our study utilized a comprehensive nationwide database to discern these differences. Method: We examined non-traumatic CAD-diagnosed patients from the U.S. National Inpatient Sample (2005-2019) using ICD-9 and ICD-10 codes. The evaluation included patient demographics, comorbidities, in-hospital complications, treatment, and costs. Differences between CCAD and VCAD were assessed using survey-weighted stepwise backward logistic regression, followed by propensity score matched adjusted regressions for outcomes. Result: From 2005 to 2019, we identified 157,086 CAD admissions, of which 79.9% (125,477) were spontaneous CADs, with CCAD outnumbering VCAD (67,671 vs. 57,806). Compared to VCAD, CCAD was significantly associated with older age (54 [44-66] vs. 49 [37-62]), Black race (12.6% vs. 8.7%), atrial fibrillation (6.1% vs. 3.7%), hypertension (58.0% vs. 53.9%), fewer concurrent acute ischemic strokes (AIS) (22.1% vs. 24.7%), higher NIHSS (mean NIHSS 7 [2-16] vs. 2 [0-5]), extended stays (4 days [2-8] vs. 4 days [2-7]) and increased hospitalization charges ($52,005 [$25,759-$118,806] vs. $43,199 [$24,116-$85,701]); all P<0.05. Within the concurrent AIS group, the CCAD group also exhibited an increased likelihood for IV thrombolysis (10.7% vs. 5.7%) and mechanical thrombectomy (14.9% vs. 3.7%). After propensity score matching for NIHSS and age, the CCAD group was associated with less death (adjusted odds ratio [aOR] 0.41, 95% CI 0.26-0.65, P<0.001) but a similar home discharge rate (aOR 1.15, 95% CI 0.78-1.69, P=0.480) (Figure). Conclusion: Our study underscores distinct comorbidity profiles and treatment patterns between CCAD and VCAD groups. These findings advocate for tailored treatment strategies based on dissection type to optimize patient outcomes.

Stress-responsive Psychobiological Markers During Pregnancy and Fetal and Infant Outcomes Across Countries

The prenatal period is a sensitive window of development that is open to both opportunity and risk for predicting later developmental outcomes. There are multiple stress-responsive physiological systems during pregnancy that may mediate the link between stress exposure and physical and mental health. Alterations in these systems during gestation due to elevated stress exposure can lead to poorer health in both the gestational parent and the offspring. In this symposium, we examine stress-responsive psychobiological systems during pregnancy and their association with differential developmental outcomes during gestation, at birth, and in infancy by a multinational group of researchers. The first presentation by the symposium chair, Özlü Aran (University of Denver, USA), will focus on the trajectories of placental corticotropin-releasing hormone (pCRH), a stress-responsive hormone released by placenta, and their association with birth outcomes as well as infant socioemotional development at 6 months postpartum. In the second presentation, Dr. Elif Aysimi Duman (Boğaziçi University, Turkey) will highlight intergenerational associations of parental early life stress and gestational parent prenatal cortisol awakening response with infant development at 4 months postpartum. This study underscores psychosocial risk (i.e., pregnancy-related worries) and protective factors (i.e., fetal bonding) in addition to prenatal HPA activity during gestation. In the third presentation, Dr. Sameera Abuaish (Princess Nourah bint Abdulrahman University, Saudi Arabia) will extend research findings beyond HPA axis by demonstrating the association between gestational parent body mass index (BMI) and prenatal mood and immune functioning, while also linking BMI to both fetal and infant outcomes. Consistent with the ISPNE’s 2023 symposium translational psychoneuroendocrinology themes, these presentations apply basic scientific methods to understand better health outcomes for gestational parents and their offspring with a focus on stress-responsive physiological systems during pregnancy. Together, they underscore the importance of early life stressors as well as prenatal stressors and their potential impact over generations among individuals across countries and cultures. Finally, these presentations will be discussed by a leading investigator, Dr. Jenalee Doom (University of Denver, USA), who has expertise on early life stress and the biological embedding of early experiences across development with a special focus on mental and physical health.

The role of androgen response pathway in association with tumor biology and response to neoadjuvant immune-checkpoint inhibitors (ICI) in muscle-invasive urothelial bladder carcinoma (MIBC).

662 Background: Emerging findings from ICI trials are suggestive of differential outcomes in females compared with males. Sex-specific differences in tumor biology, microbiome, and outcomes in MIBC are well-established. Conversely, limited data are available regarding the role of the androgen response pathway in explaining subtype differences between males and females and, most importantly, response to ICI. Methods: We retrospectively evaluated the biomarker findings of the transurethral resection of the bladder tumors (TURBT) and baseline clinical characteristics of patients (pts) with cT2-4N0M0 MIBC who received neoadjuvant pembrolizumab and radical cystectomy (RC) in the PURE-01 study. Transcriptome-wide expression profiling was performed on 102 TURBT samples. We focused on androgen receptor (AR) gene expression and the hallmark androgen response pathway expression quantifying 117 different genes related to the androgen response pathway as previously reported (PMID: 26771021). Pt and tumor characteristics were compared between subgroups using χ2 tests and two-sided Wilcoxon rank-sum tests. Kaplan-Meier curves and log rank tests evaluated gene expression and signature scores in association with the event-free survival (EFS), calculated from start of pembrolizumab treatment. Signature scores were analyzed as continuous values and were split by median and quartile values. Results: Pts received pembrolizumab and RC from 2017 to 2022. There were 87 (85.3%) males and 15 (14.7%) females. AR gene expression was not significantly different between males and females (p = 0.5), whereas androgen response signature was significantly higher in male (p = 0.03). The AR gene expression and androgen response signature scores were more highly expressed in luminal tumors vs rest of molecular subtypes (p = 0.005 and p < 0.001). Despite AR gene expression was not associated with ypT0N0 response (p = 0.425), hallmark androgen response signature scores were significantly lower in ypT0N0 responders (p = 0.033). Higher hallmark androgen response signature scores were statistically significantly associated with shorter EFS (p = 0.028), whereas AR gene expression was not (p = 0.152). Conclusions: For the first time to our knowledge, we reported the androgen response pathway expression to be a potential biomarker of ICI benefit in MIBC. This signature was also associated with a luminal subtype, linked to inferior responsiveness to ICI. If confirmed at a larger scale these analyses will strengthen the need for sex-specific approaches and potentially new combination therapies in MIBC.

Reporting of Participants' Sex, Race, Ethnicity, and Socioeconomic Status in Pituitary Surgery Literature.

Introduction Social determinants of health (SDOH) are associated with differential outcomes after pituitary tumor treatment. However, the specific impact of SDOH is not well characterized. One reason may be the lack of collection and reporting of sociodemographic variables in the literature. This study aims to evaluate the frequency of reporting and distribution of participants' sex, race, ethnicity, income, and education level within pituitary surgery literature. We will compare the reported clinical research population demographics to the 2020 U.S. census. Methods A systematic review was performed by searching PubMed, Cochrane, and Embase databases for pituitary surgery clinical research published between July 1, 2021 to June 30, 2022. We excluded studies that lacked a comparison group, were not original research (i.e., systematic reviews, meta-analysis), or included national databases and registry data. Results The final analysis included 92 studies. A total of 99% of studies collected data on subject sex. On average 49% (range: 14-100%) of study populations were male. Only 4% ( n = 4) studies included racial demographic data. Two studies included information on participants' ethnicity and two included education background. No studies included income or insurance data. Four U.S. studies included demographic distribution, and the reported race and ethnicity percentages are similar to the U.S. 2020 census distribution. Conclusion Most clinical pituitary research collects and reports data on participant sex. However, very few studies collect and report data on other sociodemographic variables that can play a role in outcomes. The lack of sociodemographic information in clinical research literature makes it difficult to determine the role of SDOH on pituitary surgery outcomes.

The role of the differential outcomes procedure and schizotypy in the recognition of dynamic facial expressions of emotions

Emotional facial expression recognition is a key ability for adequate social functioning. The current study aims to test if the differential outcomes procedure (DOP) may improve the recognition of dynamic facial expressions of emotions and to further explore whether schizotypal personality traits may have any effect on performance. 183 undergraduate students completed a task where a face morphed from a neutral expression to one of the six basic emotions at full intensity over 10 s. Participants had to press spacebar as soon as they identified the emotion and choose which had appeared. In the first block, participants received no outcomes. In the second block, a group received specific outcomes associated to each emotion (DOP group), while another group received non-differential outcomes after correctly responding (NOP group). Employing generalized linear models (GLMs) and Bayesian inference we estimated different parameters to answer our research goals. Schizotypal personality traits did not seem to affect dynamic emotional facial expression recognition. Participants of the DOP group were less likely to respond incorrectly to faces showing Fear and Surprise at fewer intensity levels. This may suggest that the DOP could lead to better identification of the main features that differentiate each facial expression of emotion.

Latent Profile Analysis of the Five Facet Mindfulness Questionnaire (FFMQ) Subscales in a Naturalistic Sample of Patients with Past or Present Major Depression: A Replication and Extension Study

ObjectivesMindfulness is a multifaceted concept which might be best captured by person-centered profiles rather than by variable-centered assessment of its subcomponents. Patients with different mindfulness profiles may vary in mental health status and might experience differential clinical outcomes of Mindfulness-Based Cognitive Therapy (MBCT). We therefore aimed to assess the relationship between mindfulness profiles and mental health in patients with major depressive disorder (MDD) and to examine whether mindfulness profiles are predictive for MBCT-induced changes in mental health.MethodLatent profile analysis (LPA), a method used to identify hidden subgroups of individuals within a population, was performed on pre-MBCT subscale scores of the Five Facet Mindfulness Questionnaire in patients with current or remitted MDD (n=754). Equality of means of pre-MBCT, post-MBCT, and residualized change scores of several mental health measures across the latent profiles was tested.ResultsLPA identified four distinct mindfulness profiles. Three profiles were similar to previously identified profiles in another MDD sample (“very low mindfulness,” “high mindfulness,” “non-judgmentally aware”) and one profile was similar to that identified in non-clinical populations (“judgmentally observing”). The “high mindfulness” subgroup scored best, the “very low mindfulness” worst, and the other subgroups intermediate on mental health in terms of depressive symptoms, worry, overall functional impairment, and self-compassion. Mindfulness profiles were not predictive of MBCT-induced changes in mental health.ConclusionsMindfulness profiles were differentially related to mental health, but were not predictive of treatment outcome. Future research would benefit from longitudinal assessment of latent mindfulness profiles to examine whether a patient’s profile changes after MBCT and whether hypothesized change in profile would be related to treatment outcome.PreregistrationThis study was not preregistered.

Ensemble Clustering to Generate Phenotypes of Kidney Transplant Donors and Recipients.

In this paper we investigate the generation of phenotypes for kidney transplant donors and recipients to assist with decision making around organ allocation. We present an ensemble clustering approach for multi-type data (numerical and categorical) using two different clustering approaches-i.e., model based and vector quantization based clustering. These clustering approaches were applied to a large, US national deceased donor kidney transplant recipient database to characterize members of each cluster (in an unsupervised fashion) and to determine whether the subsequent risk of graft failure differed for each cluster. We generated three distinct clusters of recipients, which were subsequently used to generate phenotypes. Each cluster phenotype had recipients with varying clinical features, and the risk of kidney transplant graft failure and mortality differed across clusters. Importantly, the clustering results by both approaches demonstrated a significant overlap. Utilization of two distinct clustering approaches may be a novel way to validate unsupervised clustering techniques and clustering can be used for organ allocation decision making on the basis of differential outcomes.

Association Between Anesthesiologist Sex and Patients' Postoperative Outcomes: A Population-based Cohort Study.

To examine the association of anesthesiologist sex on postoperative outcomes. Differences in patient postoperative outcomes exist, depending on whether the primary surgeon is male or female, with better outcomes seen among patients treated by female surgeons. Whether the intraoperative anesthesiologist's sex is associated with differential postoperative patient outcomes is unknown. We performed a population-based, retrospective cohort study among adult patients undergoing one of 25 common elective or emergent surgical procedures from 2007 to 2019 in Ontario, Canada. We assessed the association between the sex of the intraoperative anesthesiologist and the primary end point of the adverse postoperative outcome, defined as death, readmission, or complication within 30 days after surgery, using generalized estimating equations. Among 1,165,711 patients treated by 3006 surgeons and 1477 anesthesiologists, 311,822 (26.7%) received care from a female anesthesiologist and 853,889 (73.3%) from a male anesthesiologist. Overall, 10.8% of patients experienced one or more adverse postoperative outcomes, of whom 1.1% died. Multivariable adjusted rates of the composite primary end point were higher among patients treated by male anesthesiologists (10.6%) compared with female anesthesiologists (10.4%; adjusted odds ratio 1.02, 95% CI: 1.00-1.05, P =0.048). We demonstrated a significant association between sex of the intraoperative anesthesiologist and patient short-term outcomes after surgery in a large cohort study. This study supports the growing literature of improved patient outcomes among female practitioners. The underlying mechanisms of why outcomes differ between male and female physicians remain elusive and require further in-depth study.

May I Help You? The Relationship Between Interpersonal Emotion Regulation and Emotional and Relational Wellbeing in Daily Life

People often get support from others in regulating their emotions, a phenomenon known as interpersonal emotion regulation (IER). However, the relative effectiveness of specific IER strategies for improving emotional and relational wellbeing in daily life is unclear. Here, we report two preregistered, ecological momentary assessment studies, in which we examined how the use of six key IER strategies relates to emotional and relational wellbeing among romantic couples in daily life. Study 1 focused on enacted IER as reported by the regulator, whereas Study 2 focused on perceived IER as reported by the regulated partner. Using a dyadic experience sampling design (6 beeps/day for 7 days), Study 1 (N = 136) showed that when people reported to have given advice or encouraged their partner to suppress their emotions, their partners experienced impaired emotional wellbeing. When people reported to have distracted their partner, their partner experienced enhanced positive affect and felt closer to their partner. The use of interpersonal reappraisal, acceptance and ignoring was unrelated to partners’ momentary wellbeing. Using a dyadic daily diary design (1 beep/day for 12 days), Study 2 (N = 361) showed that perceptions of one’s emotions being ignored by the partner were associated with impaired emotional and relational wellbeing on the same day. The perceived use of other IER strategies was unrelated to momentary wellbeing. Taken together, the present set of studies illuminates how IER processes shape people’s emotions and relationships in ecologically valid settings. Our findings indicate that enacted and perceived regulatory behaviors are associated with differential outcomes, highlighting the complex nature of interpersonal emotion dynamics.

Multi-locus sequence analysis reveals phylogenetically segregated Entamoeba histolytica population.

Amoebiasis, caused by the enteric parasite, Entamoeba histolytica, is one of the major food- and water-borne parasitic diseases in developing countries with improper sanitation and poor hygiene. Infection with E. histolytica has diverse disease outcomes, which are determined by the genetic diversity of the infecting strains. Comparative genetic analysis of infecting E. histolytica strains associated with differential disease outcomes from different geographical regions of the world is important to identify the specific genetic patterns of the pathogen that trigger certain disease outcomes of Amoebiasis. The strategy is able to elucidate the genealogical relation and population structure of infecting E. histolytica strains from different geographical regions. In the present study, we have performed a comparative genetic analysis of circulating E. histolytica strains identified from different parts of the world, including our study region, based on five tRNA-linked short tandem repeat (STR) loci (i.e., D-A, NK2, R-R, STGA-D and A-L) and evaluated their potential associations with differential disease outcomes of Amoebiasis. A number of regional-specific, emerging haplotypes of E. histolytica, significantly associated with specific disease outcomes have been identified. Haplotypes, which have a significant positive association with asymptomatic and amoebic liver abscess outcomes, showed a significant negative association with diarrheal outcome, or vice versa. Comparative multi-locus analysis revealed that E. histolytica isolates from our study region are phylogenetically segregated from the isolates of other geographical regions. This study provides a crucial overview of the population structure and emerging pattern of the enteric parasite, E. histolytica.

Physical Activity and Health of Middle-Aged and Older Japanese Across the COVID-19 Pandemic: Differential Outcomes Highlight a Problematic Life Stage.

COVID-19 caused major disruptions across the super-aged nation of Japan, yet few studies explored temporal changes among middle-aged and older cohorts from baseline to the height of community transmission. Changes in physical activity and sedentary behavior during global pandemics may alter patterns of morbidity and mortality among susceptible aging populations. This study investigated patterns of physical activity, sitting behavior, and health among representative samples of middle-aged and older adults in Tokyo before and during the pandemic. Repeated online surveys were conducted with quota samples of 800 Tokyo residents in 2019 and 2021 using validated Japanese-language measures, including the short form-International Physical Activity Questionnaire and the Basic Ecological Health Scale-6. Statistical analyses included comparative evaluations of activity parameters by age cohort, gender, and selected covariates. Statistical tests included the Kruskal-Wallis test, Mann-Whitney U test, chi-square test for Independence and Hierarchical Regression. Over 34% of respondents were inactive at each data collection point, and 72% reported negative impacts of COVID-19 on their physical activities. Older adults showed no significant changes in their activity and sitting behavior and reported better health compared with those in middle age across the pandemic. Middle-aged males reported a significant decline in total activity of 33% across the pandemic period (U = 16,958, z = -2.64, p = .008, r = .13). Middle-aged females reported the lowest levels of physical activity, and health, and showed a 29% increase in sitting behavior across the pandemic (U = 16,925, z = -2.68, p = .007, r = .13). Subjective health status was consistently associated with higher overall activity and walking before and during the pandemic. Differential outcomes were identified between age and gender regarding health, physical activity, walking, and sitting across the pandemic with significantly worse impacts reported among middle-aged samples. These results have implications for healthy transitions to later life and the design of postpandemic interventions to address activity opportunities in Japan.

It’s About Time, Part II: Does Time Poverty Contribute to Inequitable College Outcomes by Gender and Race/Ethnicity?

Existing research demonstrates gender- and race/ethnicity-based inequities in college outcomes. Separately, recent research suggests a relationship between time poverty and college outcomes for student parents and online students. However, to date, no studies have empirically explored whether differential access to time as a resource for college may explain differential outcomes by gender or race/ethnicity. To address this, this study explored the relationship between time poverty, gender or race/ethnicity, and college outcomes at a large urban public university with two and four year campuses. Time poverty explained a significant proportion of differential outcomes (retention and credit accumulation) by gender and race/ethnicity. More time-poor groups also dedicated a larger proportion of their (relatively limited) discretionary time to their education, suggesting that inequitable distributions of time may contribute to other negative outcomes (e.g., reduced time for sleep, exercise, healthcare). This suggests that time poverty is a significant but understudied equity issue in higher education.

Education, health indicators and fertility outcomes: a longitudinal analysis of couples in Britain.

Previous studies have shown that highly educated women are more likely to realise their fertility aspirations, or experience a faster progression to a higher order birth, compared to lower educated women. This is often explained by improved economic or social resources among the higher educated. However, it is unclear whether educational differences in health behaviours may also contribute to these differential fertility outcomes. In this study, we use data from Waves 1-7 of the UK Longitudinal Household Study, combined with data from the Nurse Health Assessment from Wave 2 to estimate couples' likelihood of experiencing additional childbirth within six years. A discrete-time event history model is employed to analyse the transition to a higher order birth, while accounting for both partners' level of education as well as smoking patterns and body mass index. We find that couples in which the female partner is highly educated are more likely to experience childbirth within six years compared to others. In addition, female smoking is negatively associated with the likelihood of childbirth, while no significant effect has been found for male health factors. Female health indicators explain some of the variation in fertility outcomes for women with lower secondary education compared to degree-educated women. However, education remains a significant predictor of the transition to higher order births, also after accounting for male and female health indicators. It is therefore important to consider both socio-economic and health factors in order to understand variations in fertility outcomes.

Tumor volume features predict survival outcomes for patients diagnosed with diffuse intrinsic pontine glioma.

Diffuse intrinsic pontine glioma (DIPG) is a fatal childhood central nervous system tumor. Diagnosis and monitoring of tumor response to therapy is based on magnetic resonance imaging (MRI). MRI-based analyses of tumor volume and appearance may aid in the prediction of patient overall survival (OS). Contrast-enhanced T1- and FLAIR/T2-weighted MR images were retrospectively collected from children with classical DIPG diagnosed by imaging (n = 43 patients). MRI features were evaluated at diagnosis (n = 43 patients) and post-radiation (n = 40 patients) to determine OS outcome predictors. Features included 3D tumor volume (Twv), contrast-enhancing tumor core volume (Tc), Tc relative to Twv (TC/Twv), and Twv relative to whole brain volume. Support vector machine (SVM) learning was used to identify feature combinations that predicted OS outcome (defined as OS shorter or longer than 12 months from diagnosis). Features associated with poor OS outcome included the presence of contrast-enhancing tumor at diagnosis, >15% Tc/Twv post-radiation therapy (RT), and >20% ∆Tc/Twv post-RT. Consistently, SVM learning identified Tc/Twv at diagnosis (prediction accuracy of 74%) and ∆Tc/Twv at <2 months post-RT (accuracy = 75%) as primary features of poor survival. This study demonstrates that tumor imaging features at diagnosis and within 4 months of RT can predict differential OS outcomes in DIPG. These findings provide a framework for incorporating tumor volume-based predictive analyses into the clinical setting, with the potential for treatment customization based on tumor risk characteristics and future applications of machine-learning-based analysis.

Enhancing Geometry Teaching in STEAM Education with Interactive Learning Environments

In confronting the challenge of effectively integrating technology into mathematics education, this study investigates the impact of GeoGebra, an interactive learning tool, on enhancing the understanding of geometry among high school students. Through a rigorous mixed-methods approach, involving 150 students segmented into control and experimental cohorts, this research meticulously assesses the differential outcomes attributable to GeoGebra engagement. Notably, our findings illuminate a significant augmentation in the experimental group’s grasp of geometric concepts, with a pronounced improvement in correlating algebraic and graphical representations of trigonometric functions. This advancement was not merely academic, it corresponded with elevated levels of student engagement and performance. Beyond the anticipated benefits of interactive tools in educational settings, our study contributes novel insights into the specific advantages of GeoGebra within the STEAM curriculum. The results advocate for a more pronounced integration of technology-enhanced learning environments in educational systems, aiming to not only enrich students’ learning experiences but also to prepare them more effectively for the complexities of modern scientific and mathematical problem-solving.

Otolaryngology Care Disparities in American Indian Populations.

Our objectives were to quantify geographical disparities in otolaryngology care access with respect to American Indian (AI) populations and to identify gaps in care. Although increased incidence and mortality rates of ear, nose, and throat (ENT) conditions in AI populations are well documented, few studies address factors contributing to these differential outcomes. We conducted a cross-sectional study of US states with AI areas that either met the population threshold for the American Community Survey annual estimate or annual supplemental estimate. A 2-tailed t test was used to compare the geographic distribution of ENT providers practicing within AI areas against non-AI areas, showing a statistically significant difference (P < .001) in the concentration of providers (0.409 vs 2.233 providers per 100,000 patients). To our knowledge, this is the first study to explore geographic barriers contributing to AI disparities within otolaryngology.

Differential outcomes of re-stratified high-risk prostate cancer patients treated with external beam radiation therapy plus high-dose-rate brachytherapy boost.

We report outcomes of high-risk prostate cancer (PCa) patients, initially classified according to a 3-tier NCCN classification system, treated with external beam radiation therapy (EBRT) and high-dose-rate brachytherapy boost (HDR-BT). Patients were analyzed based on a re-stratification of their risk grouping using CAPRA score and a newer 5-tier NCCN classification. 471 high-risk PCa patients treated with EBRT, HDR-BT, and androgen deprivation therapy (ADT) between 1999 and 2018 were included. Competing risk survival analyses to compare individuals with CAPRA scores < 6 vs. ≥ 6 for biochemical relapse (BCR) and metastasis incidence were conducted. Also, overall survival (OS) for both groups using Kaplan-Meier analysis was assessed. The same analyses were repeated using a 5-tier NCCN stratification comparing those classified as high-risk vs. very high-risk patients. The median age was 71 years, and the median follow-up period was 72 months. The whole cohort received an EQD2 of 74 Gy or greater, with a median EQD2 of 106.89 Gy. Both a CAPRA score ≥ 6 and belonging to the NCCN very high-risk group were associated with BCR, with subdistribution hazard ratios (sHRs) of 3.04 (p = 0.015) and 2.53 (p = 0.013), respectively. For metastasis incidence, both the CAPRA and NCCN groups had similar sHRs of 2.60 (p = 0.094) and 2.71 (p = 0.037), respectively. For 10-year OS, patients with CAPRA score ≥ 6 and belonging to the NCCN very high-risk group presented similar HRs of 2.11 (p = 0.005) and 2.10 (p = 0.002). We showed that high-risk PCa patients classified according to the 3-tier NCCN system benefit from further stratification using the CAPRA score or the 5-tier NCCN stratification method. Patients with a CAPRA score ≥ 6 or classified as very high-risk demonstrate a higher hazard of BCR, metastasis, and death. These patients might benefit from further intensification of their investigations and treatment, based on ongoing research.

Design Considerations for Facilitating Equitable Participation in an Ethical Data Science Course for High School Students

The emergence of data science, Big Data Analytics, and other related methodologies have resulted in differential outcomes for people situated differently in society. Exacerbating these effects is the privilege hazard (D’Ignazio &amp; Klein, 2020) that occurs when teams of data scientists are composed primarily of individuals from privileged backgrounds. Therefore, the purpose of this article is to understand how educators may support students from different backgrounds (both relatively privileged and marginalized) to participate equitably and meaningfully in ethical data science discussions in order to safeguard against the privilege hazard. To do this, we draw on the literature regarding STEM identity formation, use Cobb and Yackel’s (1996) framework for analyzing social norms for discourse in inquiry-based classrooms, and draw on Hodge and Cobb’s Cultural Participation Orientation towards developing an inclusive classroom environment. Finally, we describe the course design elements (task structures, participation structures, and discursive moves) that supported students’ equitable participation in ethical data science discussions (Sandoval, 2004).

Differential Outcomes of Infection by Wild-Type SARS-CoV-2 and the B.1.617.2 and B.1.1.529 Variants of Concern in K18-hACE2 Transgenic Mice.

SARS-CoV-2 is a respiratory virus with neurological complications including the loss of smell and taste, headache, and confusion that can persist for months or longer. Severe neuronal cell damage has also been reported in some cases. The objective of this study was to compare the infectivity of the wild-type virus, Delta (B.1.617.2) and Omicron (B.1.1.529) variants in transgenic mice that express the human angiotensin-converting enzyme 2 (hACE2) receptor under the control of the keratin 18 promoter (K18) and characterize the progression of infection and inflammatory response in the lungs, brain, medulla oblongata, and olfactory bulbs of these animals. We hypothesized that wild type, Delta and Omicron differentially infect K18-hACE2 mice, thereby inducing distinct cellular responses. K18-hACE2 female mice were intranasally infected with wild-type, Delta, or Omicron variants and euthanized either at 3 days post-infection (dpi) or at the humane endpoint. None of the animals infected with the Omicron variant reached the humane endpoint and were euthanized at day 8 dpi. Virological and immunological analyses were performed in the lungs, brains, medulla oblongata and olfactory bulbs isolated from infected mice. At 3 dpi, mice infected with wild type and Delta displayed significantly higher levels of viral RNA in the lungs than mice infected with Omicron, while in the brain, Delta and Omicron resulted in higher levels of viral RNA than with the wild type. Viral RNA was also detected in the medulla oblongata of mice infected by all these virus strains. At this time point, the mice infected with wild type and Delta displayed a marked upregulation of many inflammatory markers in the lungs. On the other hand, the upregulation of inflammatory markers was observed only in the brains of mice infected with Delta and Omicron. At the humane endpoint, we observed a significant increase in the levels of viral RNA in the lungs and brains of mice infected with wild type and Delta, which was accompanied by the elevated expression of many inflammatory markers. In contrast, mice which survived infection with the Omicron variant showed high levels of viral RNA and the upregulation of cytokine and chemokine expression only in the lungs at 8 dpi, suggesting that infection and inflammatory response by this variant is attenuated in the brain. Reduced RNA levels and the downregulation of inflammatory markers was also observed in the medulla oblongata and olfactory bulbs of mice infected with Omicron at 8 dpi as compared with mice infected with wild-type and Delta at the humane end point. Collectively, these data demonstrate that wild-type, Delta, and Omicron SARS-CoV-2 induce distinct levels of infection and inflammatory responses in K18-hACE2 mice. Notably, sustained brain infection accompanied by the upregulation of inflammatory markers is a critical outcome in mice infected with wild type and Delta but not Omicron.