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The purpose of this qualitative participatory research study was to explore what happens when English language arts (ELA) preservice teachers collaborate to develop multimodal, intersectional, and critical feminist empowerment literacy curricula. This study centered on the following research question: How do ELA preservice teachers make sense of how pop-cultural, multimodal texts such as VSCO stickers frame girlhood and womanhood? Multiple data were collected: audio and video recording transcripts of monthly Saturday workshops, artifacts, such as curriculum writing and workshop photographs, researcher journals, analytic memos, and a shared Google Drive of written student thinking. The constant comparative method was used to analyze and triangulate the data. Analyses of data revealed that preservice teachers were able to critically analyze consumerism relating to VSCO stickers and girlhood and were able to notice how stickers typecast and reify individualism while also navigating authenticity during self-selection and categorizing stickers. Additionally, data analysis demonstrated how critical literacies played a role in the preservice teachers' understanding of how several groups, communities, and individual voices were not recognized in the marketing and consumption of VSCO sticker packaging as well as providing additional gender biases in society.

In this discussion, we argue for those who are literacy educators to reframe gossip as a dialogic, feminist act in their teaching and interpretation of gossip as framed in the literature they teach in secondary English language arts (ELA) classrooms. Reframing gossip as a feminist act invites meaning-makers to view those conversations and generative dialogues discursively gendered in deficit ways (or gossip) as proactive, productive, and powerful tools of connection between and within societies and communities. We share how we centered and created through a critical feminist lens, an ELA curriculum that supports gossip as a literary tool that drives narratives in plot formation, as well as a means to enhance characters' positions, personalities, allies, and enemies within a story. Most importantly, we use gossip as an analytical tool to reframe and promote gender equity, guiding preservice teachers and adolescents in critical analysis of the innumerable ways systems and institutions of power and privilege -- such as race, ethnicity, religion, and sexuality -- intersect in the fight for gender equality. First, we will discuss our guiding theoretical framework of critical feminist pedagogy to examine the ELA curriculum. Next, we share how the development of a curricular unit on reframing gossip in literature unfolded organically through a monthly Saturday workshop called "Writing Us In: Developing Critical Literacy Curriculum for ELA Classrooms." Then, we showcase how one preservice ELA teacher applied the critical feminist lenses examined within the workshop space to develop a linked text set and subsequent ELA curricular unit with the aims of her future students to critically analyze, from a feminist lens, how gossip is portrayed in society and how it is framed in literature. We end with a discussion of how our spotlight student reflects on this project and her key takeaways.

Best practice for the assessment of autism spectrum disorder (ASD) symptom severity relies on clinician ratings of the Autism Diagnostic Observation Schedule, 2nd Edition (ADOS-2), but the association of these ratings with objective measures of children's social gaze and smiling is unknown. Sixty-six preschool-age children (49 boys, M = 39.97 months, SD = 10.58) with suspected ASD (61 confirmed ASD) were administered the ADOS-2 and provided social affect calibrated severity scores (SA CSS). Children's social gaze and smiling during the ADOS-2, captured with a camera contained in eyeglasses worn by the examiner and parent, were obtained via a computer vision processing pipeline. Children who gazed more at their parents (p = 0.04) and whose gaze at their parents involved more smiling (p = 0.02) received lower social affect severity scores, indicating fewer social affect symptoms, adjusted R[superscript 2] = 0.15, p = 0.003.

PURPOSE: Locally advanced/metastatic urothelial cancer (la/mUC) affects patients quality of life (QOL) and functioning. We describe the impact of first-line (1L) enfortumab vedotin (EV) alone or with pembrolizumab (P) on QOL/functioning/symptoms in patients with la/mUC who were cisplatin-ineligible from EV-103 Cohort K. METHODS: In this phase Ib/II trial, patients were randomly assigned 1:1 to EV + P or EV monotherapy (mono). Exploratory patient-reported outcomes (PROs) were assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questionnaire (EORTC QLQ-C30) and Brief Pain Inventory Short Form (BPI-SF) at baseline, once per week for cycles 1-3, and then in every cycle through the end of treatment. Changes in scores from baseline to week 24, reported as least squares mean (standard error), were assessed by mixed models for repeated measures. There were no formal statistical comparisons between treatment arms. RESULTS: Of 149 patients treated, 65 (EV + P) and 63 (EV mono) comprised the PRO analysis set. For EV + P, EORTC QLQ-C30 QOL was maintained through week 24 with improvements in emotional functioning, pain, and insomnia. Clinically meaningful improvements were seen in EORTC QLQ-C30 pain after EV + P at weeks 12 (-14.41 [3.14]) and 24 (-14.99 [3.56]) and BPI-SF worst pain at week 24 (-2.07 [0.37]). For EV mono, EORTC QLQ-C30 QOL remained stable with clinically meaningful improvements in EORTC QLQ-C30 pain (-12.55 [4.27]), insomnia (-14.46 [4.69]), and constipation (-10.09 [4.35]) at week 24. There were small-to-moderate improvements in BPI-SF worst pain at week 24. CONCLUSION: EV + P in patients with la/mUC who were cisplatin-ineligible was associated with preservation or improvement of QOL/functioning/symptoms. Improvement in pain was seen in both PRO instruments and treatment arms. These data complement clinical outcomes of 1L EV + P.

Endogenous retroviruses (ERVs) are remnants of ancient parasitic infections and comprise sizable portions of most genomes. Although epigenetic mechanisms silence most ERVs by generating a repressive environment that prevents their expression (heterochromatin), little is known about mechanisms silencing ERVs residing in open regions of the genome (euchromatin). This is particularly important during embryonic development, where induction and repression of distinct classes of ERVs occur in short temporal windows. Here, we demonstrate that transcription-associated RNA degradation by the nuclear RNA exosome and Integrator is a regulatory mechanism that controls the productive transcription of most genes and many ERVs involved in preimplantation development. Disrupting nuclear RNA catabolism promotes dedifferentiation to a totipotent-like state characterized by defects in RNAPII elongation and decreased expression of long genes (gene-length asymmetry). Our results indicate that RNA catabolism is a core regulatory module of gene networks that safeguards RNAPII activity, ERV expression, cell identity, and developmental potency.

The disproportionate use of chemical straighteners and skin lighteners by women of color is a growing public health concern given the link between product use and adverse health effects. Prior studies examined product use as an individual choice but neglected social-structural factors, which influence beauty perceptions and personal decisions around product use. We used a community-based participatory research approach to characterize product use by demographics and investigated how racialized beauty norms impact use among 297 women and femme-identifying individuals in Northern Manhattan and the South Bronx. Product use varied by race/ethnicity, nativity, and messaging from family and peers. Black respondents were more likely to ever use chemical straighteners than non-Black respondents (OR = 2.0; 95% CI = 1.2-3.2), as were respondents who heard that family members express a preference for straight hair compared with respondents whose family members expressed mixed preferences about hairstyles (OR = 2.0; 95% CI = 1.1-3.7). Compared with non-Asian respondents and respondents born in the United States, Asian respondents and respondents born in other countries, respectively, had threefold higher odds of ever using skin lighteners (Asian: OR = 3.2; 95% CI = 1.4-7.0; born in other countries: OR = 3.4; 95% CI = 1.9-6.1). Respondents' perceptions that others believe straight hair or lighter skin confer benefits such as beauty, professionalism, or youth were associated with greater use of chemical straighteners and skin lighteners. These findings highlight the pervasiveness of racialized beauty norms and point to the need to reduce the demand for and sale of these products through community education, market-based strategies, and public policy.

Abstract Objective We aimed to validate the Japanese version of the Patient Health Questionnaire-4 (PHQ-4-J). People in Japan, especially healthcare workers (HCWs) suffer from high rates of mental health symptoms. The PHQ-4 is an established ultra-brief mental health measure used in various settings, populations and languages. The Japanese version of the PHQ-4 has not been validated. Methods Two hundred eighty people in Japan (142 HCWs and 138 from the general public) responded to the PHQ-4-J. Internal consistency, and factorial validity were assessed using confirmatory factor analysis (CFA) and Multiple Indicators Multiple Causes (MIMIC) models. Results Internal consistency was high (α = 0.70–0.86). CFA yielded very good fit indices for a two-factor solution (RMSEA = 0.04, 95% CI 0.00–0.17) and MIMIC models indicated the performance differed between HCWs and the general population. Conclusions The PHQ-4-J is a reliable ultra-brief scale for depression and anxiety in Japanese, which can be used to meet current needs in mental health research and practice in Japan. Disaster research and gerontology research can benefit from this scale, enabling mental health assessment with little participant burden. In practice, early detection and personalised care can be facilitated by using the scale. Future research should target specific populations in Japan during a non-emergency time.

Abstract The role of rare non-coding variation in complex human phenotypes is still largely unknown. To elucidate the impact of rare variants in regulatory elements, we performed a whole-genome sequencing association analysis for height using 333,100 individuals from three datasets: UK Biobank (N = 200,003), TOPMed (N = 87,652) and All of Us (N = 45,445). We performed rare (

Abstract Myocardial ischemia causes the release of bradykinin, which activates afferent nerve endings in the ventricular epicardium. This elicits a sympathetically mediated increase in arterial pressure and heart rate, referred to as the cardiogenic sympathetic afferent reflex. The rostroventrolateral medulla (RVLM) is a key sympathetic brain stem site for regulating cardiovascular activity. This study aimed to determine the importance of non‐barosensitive nociception sympathetic activity and the role of glutamate receptor activation of RVLM neurons in the cardiogenic sympathetic afferent reflex. We tested the hypothesis that inhibition of barosensitive sympathetic activity attenuates but does not abolish the reflex response to cardiac visceral afferents. Renal sympathetic nerve activity (RSNA), arterial pressure, and heart rate responses to epicardial bradykinin application were recorded in anesthetized rats before and after bilateral RVLM microinjection of either GABAA agonist muscimol, ionotropic glutamate receptor antagonist kynurenic acid, N‐methyl‐d‐aspartate (NMDA) receptor antagonist 2‐amino‐5‐ phosphonopentanoic acid (AP5), or non‐NMDA antagonist 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX). Baroreceptor loading‐induced inhibition of barosensitive activity attenuated the bradykinin‐induced RSNA response (93 ± 14% increase) and tachycardia (18 ± 3 bpm). While RVLM muscimol microinjection abolished the RSNA response (1.6 ± 4.2% from baseline, 0.49 ± 0.38 μV*s), surprisingly, it did not abolish the tachycardia (27 ± 4 bpm). Kynurenic acid microinjection blocked the arterial pressure and RSNA responses, while AP5 or CNQX only attenuated the responses. These data suggest that nociception‐sensitive sympathetic activity that does not appear to be barosensitive is also involved in the cardiogenic sympathetic afferent reflex. Importantly, while muscimol and kynurenic acid abolished the arterial pressure and RSNA response, neither affected the tachycardia, suggesting an alternate cardiac pathway independent of RVLM.

Abstract Drug-induced gene expression profiles can identify potential mechanisms of toxicity. We focus on obtaining signatures for cardiotoxicity of FDA-approved tyrosine kinase inhibitors (TKIs) in human induced-pluripotent-stem-cell-derived cardiomyocytes, using bulk transcriptomic profiles. We use singular value decomposition to identify drug-selective patterns across cell lines obtained from multiple healthy human subjects. Cellular pathways affected by cardiotoxic TKIs include energy metabolism, contractile, and extracellular matrix dynamics. Projecting these pathways to published single cell expression profiles indicates that TKI responses can be evoked in both cardiomyocytes and fibroblasts. Integration of transcriptomic outlier analysis with whole genomic sequencing of our six cell lines enables us to correctly reidentify a genomic variant causally linked to anthracycline-induced cardiotoxicity and predict genomic variants potentially associated with TKI-induced cardiotoxicity. We conclude that mRNA expression profiles when integrated with publicly available genomic, pathway, and single cell transcriptomic datasets, provide multiscale signatures for cardiotoxicity that could be used for drug development and patient stratification.

Abstract Reader variability is intrinsic to radiologic oncology assessments, necessitating measures to enhance consistency and accuracy. RECIST 1.1 criteria play a crucial role in mitigating this variability by standardizing evaluations, aiming to establish an accepted “truth” confirmed by histology or patient survival. Clinical trials utilize Blind Independent Centralized Review (BICR) techniques to manage variability, employing double reads and adjudicators to address inter-observer discordance effectively. It is essential to dissect the root causes of variability in response assessments, with a specific focus on the factors influencing RECIST evaluations. We propose proactive measures for radiologists to address variability sources such as radiologist expertise, image quality, and accessibility of contextual information, which significantly impact interpretation and assessment precision. Adherence to standardization and RECIST guidelines is pivotal in diminishing variability and ensuring uniform results across studies. Variability factors, including lesion selection, new lesion appearance, and confirmation bias, can have profound implications on assessment accuracy and interpretation, underscoring the importance of identifying and addressing these factors. Delving into the causes of variability aids in enhancing the accuracy and consistency of response assessments in oncology, underscoring the role of standardized evaluation protocols and mitigating risk factors that contribute to variability. Access to contextual information is crucial. Critical relevance statement By understanding the causes of diagnosis variability, we can enhance the accuracy and consistency of response assessments in oncology, ultimately improving patient care and clinical outcomes. Key Points Baseline lesion selection and detection of new lesions play a major role in the occurrence of discordance. Image interpretation is influenced by contextual information, the lack of which can lead to diagnostic uncertainty. Radiologists must be trained in RECIST criteria to reduce errors and variability. Graphical Abstract

Erin Parisi is attempting to become the first trans* person to ascent the highest mountain on each of the seven continents, through her project TranSending 7. Erin seeks to create alternative trans* narratives that are based on the possibility of positive futures, as opposed to negative tropes of a limited life from the decision to transition. Multiple semi-structured interviews were conducted with Erin to understand her experiences and how narratives she hopes to present, not only impact upon her own sense of self, health and well-being but also present opportunities for others. Data were analysed via "reflexive" thematic analysis. Analysis highlights for Erin a paradox for many trans* people in moving from one closet to another, where being "invisible" as a trans* person is the ultimate goal. Erin's desire to shape positive trans* narratives acknowledge the gendering practices that take place within the climbing community and a sense of her having to 'earn the right to climb'. Erin's endeavours demonstrate an alternative way individuals can be situated 'in the sunshine' between these two spaces, where personal growth is not only possible but rich, meaningful, and progressive. In drawing upon theoretical concepts informed by possible selves theory, this research seeks to untangle the gendered space of the mountain for shaping positive and transformational trans* narratives for individuals positioned within these gendered boundaries. It also seeks to identify stronger and more positive possible futures for other trans* people and youth.