Low-loss and high-index contrast ultraviolet-C free-standing waveguides made of thermal silicon oxide.

Photonics in the ultraviolet provides an avenue for key advances in biosensing, pharmaceutical research, and environmental sensing. However, despite recent progress in photonic integration, a technological solution to fabricate photonic integrated circuits (PICs) operating in the UV-C wavelength range, namely, between 200 and 280 nm, remains elusive. Filling this gap will open opportunities for new applications, particularly in healthcare. A major challenge has been to identify materials with low optical absorption loss in this wavelength range that are at the same time compatible with waveguide design and large-scale fabrication. In this work, we unveil that thermal silicon oxide (TOX) on a silicon substrate is a potential candidate for integrated photonics in the UV-C, by removing the silicon substrate under selected regions to form single-side suspended ridge waveguides. We provide design guidelines for low-loss waveguide geometries, avoiding wrinkling due to residual intrinsic stress, and experimentally demonstrate waveguides that exhibit optical propagation losses below 3 and 4 dB/cm at a wavelength of 266 nm with claddings of air and water, respectively. This result paves the way for on-chip UV-C biological sensing and imaging.

Cutoff Suppresses RNA Polymerase II Termination to Ensure Expression of piRNA Precursors.

Small non-coding RNAs called piRNAs serve as guides for an adaptable immune system that represses transposable elements in germ cells of Metazoa. In Drosophila the RDC complex, composed of Rhino, Deadlock and Cutoff (Cuff) bind chromatin of dual-strand piRNA clusters, special genomic regions, which encode piRNA precursors. The RDC complex is required for transcription of piRNA precursors, though the mechanism by which it licenses transcription remained unknown. Here, we show that Cuff prevents premature termination of RNA polymerase II. Cuff prevents cleavage of nascent RNA at poly(A) sites by interfering with recruitment of the cleavage and polyadenylation specificity factor (CPSF) complex. Cuff also protects processed transcripts from degradation by the exonuclease Rat1. Our work reveals a conceptually different mechanism of transcriptional enhancement. In contrast to other factors that regulate termination by binding to specific signals on nascent RNA, the RDC complex inhibits termination in a chromatin-dependent and sequence-independent manner.

"It's like having a superpower": Reclaiming creativity and the intersectional experiences of trans young adults of color.

Trans young adults of color experience systemic harm that contributes to negative health outcomes and hinders their ability to live freely. The present study used a grounded theory qualitative methodology rooted in a critical-ideological paradigm to understand the intersections of racial and gender oppression. Trans young adults of color from across the United States (N = 15; ages 20-29; majority racial identities: Asian, Black, and multiracial; majority gender identities: nonbinary and transmasculine) participated in a semistructured interview. Analyses identified a six-category empirical framework explaining major dimensions and processes of intersectional experiences of trans people of color. The core category, Reclaiming Creativity, reflected how trans communities of color use creativity to build their identities and communities beyond intersectional oppressive societal norms and imagine a better, more liberated world. The remaining five categories were Creating and Recreating Identity, Experiencing Discrimination and Its Impacts on Wellness, Surviving Oppression and Compromising Authentic Self, Embracing Identity Strengths, and Finding Liberation. They provided insights into the role of creativity within the intersectional experiences of trans young adults of color. In doing so, they provided directions to address structural injustice, pursue liberation, and allow creativity to flourish. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Family rejection and LGBTQ+ Asian Americans' psychological distress and disordered eating: The role of conflicts in allegiances and family shame.

OBJECTIVES: Lesbian, gay, bisexual, trans, and queer (LGBTQ+) Asian Americans experience unique psychological health concerns at the intersection of multiple forms of marginalization. White supremacist, cisheteronormative, and colonial ideals and their structural and interpersonal manifestations may encourage family rejection of LGBTQ+ identities within Asian American family units. Family shame, conflicts in allegiances, and internalized anti-LGBTQ+ stigma were hypothesized as mediators in the association between family rejection and psychological distress and disordered eating. METHOD: The present study examined family rejection and its impacts on psychological distress and disordered eating in a sample of LGBTQ+ Asian American adults (N = 155; Mage = 24.26; 30.3% gender diverse) using a cross-sectional survey design and path analysis. RESULTS: There was a significant serial mediation such that family rejection was positively associated with conflicts in allegiances, family shame, and psychological distress (B = .12, p = .01). The same serial mediation was nonsignificant for disordered eating (B = .04, p = .26). CONCLUSIONS: Results indicate the importance of considering conflicts in allegiances, family shame, and the interpersonal dynamics of LGBTQ+ Asian Americans in understanding experiences of psychological distress and disordered eating. Implications are drawn for further research, clinical work, and broader efforts addressing the larger sociocultural environment that encourages family rejection of LGBTQ+ identity. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Associations between gendered racism, racial identity, and nicotine use among Asian American men.

OBJECTIVES: The present study utilized an intersectional framework to examine if two forms of gendered racism, psychological emasculation and messages about Asian American men being undesirable partners, were associated with Asian American men's nicotine use. We also examined the potential mediating roles of two racial identity statuses, racial conformity and racial immersion. METHODS: A sample of 356 Asian American men living in the United States of America (USA) completed a cross-sectional survey via Qualtrics containing measures assessing the aforementioned constructs of interest. The primary analysis examined separate parallel mediation models, situating psychological emasculation and undesirable partner as separate independent variables, racial conformity and racial immersion as parallel mediators, nicotine use as the outcome, and age and employment as covariates. RESULTS: In separate parallel mediation models, the links between psychological emasculation and undesirable partner on one hand, and nicotine use on the other, were completely mediated only by racial conformity, and not significantly mediated by racial immersion. Specifically, greater endorsement of gendered racism was associated with greater conformity with (and internalization of) these gendered racist beliefs, which in turn were associated with greater nicotine use. CONCLUSION: Researchers and practitioners may consider racial conformity as an interventional target to ameliorate Asian American men's nicotine use. Future studies should continue to examine other culturally relevant and/or potentially protective constructs (e.g., on the basis of gender, race, and its intersection) that may mitigate Asian American men's nicotine use.

Pride and body image among transgender and nonbinary adults: the mediating role of body appreciation between gender identity pride and intuitive eating.

Studies exploring disordered eating among transgender and nonbinary populations have primarily focused on minority stressors with a dearth of research examining the role of gender identity pride on body appreciation and intuitive eating. To address this gap in the literature, the present study, comprised of 148 transgender and nonbinary adults (Mage = 24.68, SD = 6.64), tested the associations among gender identity pride, body appreciation, and intuitive eating, controlling for demographics and minority stress variables. The study also tested body appreciation as a mediator in the cross-sectional association between gender identity pride and intuitive eating. Regression models indicated that greater gender identity pride was significantly associated with greater body appreciation, but not intuitive eating. Greater body appreciation was a significant mediator in the positive association between gender identity pride and intuitive eating. Findings support the significant role and relevance of examining gender identity pride as related to body appreciation and intuitive eating. Future research may determine the causal impact of gender identity pride on body image and eating behaviors in transgender and nonbinary populations. Clinicians may consider the positive role of gender identity pride when addressing body image and eating behaviors with their transgender and nonbinary clients.

Validation of an HIV whole genome sequencing method for HIV drug resistance testing in an Australian clinical microbiology laboratory.

Detection of HIV drug resistance (HIVDR) is vital to successful anti-retroviral therapy (ART). HIVDR testing to determine drug-resistance mutations is routinely performed in Australia to guide ART choice in newly diagnosed people living with HIV or in cases of treatment failure. In 2022, our clinical microbiology laboratory sought to validate a next-generation sequencing (NGS)-based HIVDR assay to replace the previous Sanger-sequencing (SS)-based ViroSeq. NGS solutions for HIVDR offer higher throughput, lower costs and higher sensitivity for variant detection. We sought to validate the previously described low-cost probe-based NGS method (veSEQ-HIV) for whole-genome recovery and HIVDR-testing in a diagnostic setting. veSEQ-HIV displayed 100% and 98% accuracy in major and minor mutation detection, respectively, and 100% accuracy of subtyping (provided > 1000 mapped reads were obtained). Pairwise comparison exhibited low inter-and intrarun variability across the whole-genome (Jaccard index [J] = 0.993; J = 0.972) and the Pol gene (J = 0.999; J = 0.999), respectively. veSEQ-HIV met all our pre-set criteria based on WHO recommendations and successfully replaced ViroSeq in our laboratory. Scaling-down veSEQ-HIV to a limited batch size and sequencing on Illumina iSeq. 100, allowed easy implementation of the assay into the workflow of a small sequencing laboratory with minimal staff and equipment and the ability to meet clinically relevant test turn-around times. As HIVDR-testing moves from SS- to NGS-based methods and new ART drugs come to market (particularly those with targets outside the Pol region), whole-genome recovery using veSEQ-HIV provides a robust, cost-effective and "future-proof" NGS method for HIVDR-testing.

Frequency and characteristics of chemotherapy-associated thrombotic microangiopathy: Analysis from a large pharmacovigilance database.

We used the information component (IC), a disproportionate Bayesian analysis comparing the number of observed versus expected adverse drug reactions, to determine the potential association between anti-neoplastic agents and thrombotic microangiopathy (TMA). The IC025 indicates the lower end of 95% of IC, in which a value >0 suggests a disproportionality signal between the drug of interest and the adverse drug reaction. Carfilzomib had the highest IC025 for TMA among all studied chemotherapies followed by gemcitabine, mitomycin, bevacizumab, and bortezomib.

Influence of melanoma type on incidence and downstream implications of cutaneous immune-related adverse events in the setting of immune checkpoint inhibitor therapy.

BACKGROUND: Emerging evidence suggests that cutaneous immune-related adverse events (cirAEs) are associated with a survival benefit in the setting of advanced melanoma treated with immune checkpoint inhibitor (ICI) therapy. Previous studies have not examined the role of melanoma subtypes on cirAE development and downstream therapeutic outcomes. OBJECTIVE: Examine the impact of melanoma subtypes on cirAE onset and survival among ICI recipients. METHODS: Retrospective multi-institutional cohort study. Multivariate time-series regressions were utilized to assess relationships between melanoma subtype, cirAE development, and survival. RESULTS: Among 747 ICI recipients, 236 (31.6%) patients developed a cirAE. Patients with acral melanoma were less likely to develop a cirAE (hazard ratio [HR] = 0.41, P = .016) compared to patients with nonacral cutaneous melanoma. Across all melanoma subtypes, cirAEs were associated with reduced mortality (HR = 0.76, P = .042). Patients with acral (HR = 2.04, P = .005), mucosal (HR = 2.30, P < .001), and uveal (HR = 4.09, P < .001) primaries exhibited the worst survival. LIMITATIONS: Retrospective cohort study. CONCLUSION: This is the first study to demonstrate differences in cirAE development among melanoma subtypes. The presence of cirAEs was associated with better survival. Further, the lower incidence of cirAEs may be a marker of immunotherapy response, which is reflected in the association between acral melanoma and mortality.

Protracted COVID-19 pneumonitis early post-ABO incompatible kidney transplantation: Management considerations and the role of whole genome sequencing.

We present the case of a recent ABO incompatible kidney transplant recipient with persistent SARS-CoV-2 infection and pneumonitis. Serial whole genome sequencing confirmed intra-host viral evolution, which was used as a surrogate to confirm active viral replication and support re-treatment with antivirals, late in the course of infection. A prolonged course of remdesivir combined with immunosuppression modulation resulted in successful clearance of virus and clinical improvement. The diagnostic process undertaken in this case provides a useful guide for other clinicians when approaching similar patients.

Gendered racial microaggressions and emerging adult Black women's social and general anxiety: Distress intolerance and stress as mediators.

There is robust evidence that gendered racial microaggressions affect Black women's mental health. However, few studies have examined how this form of discrimination affects Black women's social anxiety in addition to their general anxiety, as well as the underlying mechanisms related to gendered racial microaggressions and anxiety. OBJECTIVE: The purpose of this study was to examine the associations between gendered racial microaggressions stress (GRMS) and gendered racial microaggressions frequency (GRMF), and Black women's social anxiety and general anxiety symptoms. We also examined the mediating roles of distress intolerance and stress in these associations. METHOD: One hundred and sixty-three Black women, between the ages of 18 and 25 years old, completed a cross-sectional survey. Regression analyses were used to examine the associations between gendered racial microaggressions and social anxiety and general anxiety, and mediation analyses examined the indirect effect of gendered racial microaggressions on the outcome variables through distress intolerance and stress. RESULTS: GRMS was associated with greater social and general anxiety through the mechanisms of distress intolerance and stress. GRMF was associated with reduced social anxiety and was not associated with general anxiety. CONCLUSIONS: Intervention efforts should be aimed to prevent the experience of gendered racial microaggressions to prevent subsequent stress and mental health outcomes for Black women.

Sexual, gendered, and internalized racism's associations with disordered eating among sexual minority Asian American men: Emotional eating as mediator.

Research related to disordered eating among sexual minority Asian American men is scarce. Thus, the present study utilized an intersectional framework to examine how three different forms of racism (i.e. sexual racism, gendered racism, and internalized racism) are associated with disordered eating among sexual minority Asian American men, as well as the mediating role of emotional eating. A cross-sectional survey containing the study's measures of interest were administered to participants. The final sample consisted of 180 sexual minority Asian American men. Both sexual racism and internalized racism were positively associated with disordered eating whereas gendered racism was not associated with disordered eating Emotional eating mediated the association between internalized racism and disordered eating, though it did not mediate the association between sexual racism and disordered eating. Researchers and practitioners are encouraged to utilize an intersectional framework that takes into account multiple forms of racism, especially sexual racism and internalized racism, when considering this underrepresented population's disordered eating. Results also demonstrate the importance of addressing racism in eating disorder prevention efforts among sexual minority Asian American men.

Health-related quality of life and economic burden of prurigo nodularis.

BACKGROUND: Prurigo nodularis (PN) is an understudied, pruritic inflammatory skin disease. Little is known about the effect of PN on quality of life and its associated economic burden. OBJECTIVE: To quantify the impact of PN on quality of life and its economic implications. METHODS: A cohort study of PN patients (n = 36) was conducted using the Health Utilities Index Mark 3 questionnaire. Control data from US adults (n = 4187) were obtained from the 2002-2003 Joint Canada/United States Survey of Health. Quality-adjusted life year loss and economic costs were estimated by comparing the Health Utilities Index Mark 3 scores of the PN patients with those of the controls. RESULTS: The PN patients had lower overall health performance compared to the controls, (mean ± SE, 0.52 ± 0.06 vs 0.86 ± 0.003, respectively, P < .001). In multivariable regression, PN was found to be associated with worse health performance (coefficient -0.34, 95% CI [-0.46 to -0.23]), most prominent in the pain subdomain (coefficient -0.24, 95% CI [-0.35 to -0.13]). This correlated to an average of 6.5 lifetime quality-adjusted life years lost per patient, translating to an individual lifetime economic burden of $323,292 and a societal burden of $38.8 billion. CONCLUSION: These results demonstrate that PN is associated with significant quality-of-life impairment, similar to the level of other chronic systemic conditions. PN is also associated with a substantial individual economic burden, emphasizing the necessity of research on effective treatment options.

Disruption of IRE1α through its kinase domain attenuates multiple myeloma.

Multiple myeloma (MM) arises from malignant immunoglobulin (Ig)-secreting plasma cells and remains an incurable, often lethal disease despite therapeutic advances. The unfolded-protein response sensor IRE1α supports protein secretion by deploying a kinase-endoribonuclease module to activate the transcription factor XBP1s. MM cells may co-opt the IRE1α-XBP1s pathway; however, the validity of IRE1α as a potential MM therapeutic target is controversial. Genetic disruption of IRE1α or XBP1s, or pharmacologic IRE1α kinase inhibition, attenuated subcutaneous or orthometastatic growth of MM tumors in mice and augmented efficacy of two established frontline antimyeloma agents, bortezomib and lenalidomide. Mechanistically, IRE1α perturbation inhibited expression of key components of the endoplasmic reticulum-associated degradation machinery, as well as secretion of Ig light chains and of cytokines and chemokines known to promote MM growth. Selective IRE1α kinase inhibition reduced viability of CD138+ plasma cells while sparing CD138- cells derived from bone marrows of newly diagnosed or posttreatment-relapsed MM patients, in both US- and European Union-based cohorts. Effective IRE1α inhibition preserved glucose-induced insulin secretion by pancreatic microislets and viability of primary hepatocytes in vitro, as well as normal tissue homeostasis in mice. These results establish a strong rationale for developing kinase-directed inhibitors of IRE1α for MM therapy.

US medical student perspectives on asian american patient inclusion in medical education: a qualitative Study.

BACKGROUND: Asian American (AsAm) representation is lacking in conversations surrounding cultural humility in healthcare. We aimed to investigate US medical student perspectives on AsAm patient inclusion in cultural humility training in medical education. METHODS: This qualitative study analyzed free-text responses to an optional, open-ended question presented at the conclusion of an online survey assessing medical student experiences with and perceptions regarding AsAm patients in their medical education. This survey was distributed to a convenience sample of nine US medical schools. Medical students who completed at least one clinical rotation were eligible to participate in the survey. Qualitative analysis of free-text responses was conducted in an iterative process to generate emergent themes. RESULTS: There was a total of 195 optional free-text responses from 688 participants (28%). Motivation to learn about AsAm population included shared identity and desire to better serve the AsAm population in their local community and future careers. Topics of interest included healthcare-related cultural preferences, healthcare delivery strategies, and health disparities for the AsAm population and other minority patients. Students reported that they drew on personal experiences and some pre-clinical or clinical exposures to learn about AsAm patients. Respondents cited the lack of exposure in the medical school curriculum and clinical experiences as the main challenge to learning about AsAm health and provided suggestions for the delivery of this education in their pre-clinical and clinical education. Respondents emphasized that AsAms are treated as a monolith in medical education and healthcare, despite their heterogeneity. CONCLUSIONS: Medical students identified a need and interest for greater inclusion of AsAm topics in medical education on cultural humility and minority health.

Body positivity for Asian Americans: Development and evaluation of the pride in Asian American Appearance Scale.

While a growing body of literature has examined factors that contribute to Asian Americans' negative body image, little research has investigated Asian Americans' body image from a strengths-based perspective. This study thus presents the Pride in Asian American Appearance Scale (PAAAS), which was designed to measure the extent to which Asian Americans feel positively about their own racialized physical appearances as well as those of fellow Asian Americans. Items were developed through an extensive literature review, cognitive interviews, and expert feedback. Exploratory (N = 398) and confirmatory (N = 398) factor analyses suggested a bifactor model, consisting of 24 items comprising a general factor and four group factors: (a) Pride in Asian Features, (b) Preference for Asian American Appearance, (c) Asian Americans as Desirable, and (d) Action Promoting Asians' Attractiveness. Internal consistency estimates as well as factor determinacies were high and demonstrated that the specified items adequately represented their intended factors. The PAAAS was significantly correlated in theoretically expected directions with collective self-esteem, internalized racist appearance bias, and psychological distress. Implications of these findings and suggestions for future research are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Transgenerationally inherited piRNAs trigger piRNA biogenesis by changing the chromatin of piRNA clusters and inducing precursor processing.

Small noncoding RNAs that associate with Piwi proteins, called piRNAs, serve as guides for repression of diverse transposable elements in germ cells of metazoa. In Drosophila, the genomic regions that give rise to piRNAs, the so-called piRNA clusters, are transcribed to generate long precursor molecules that are processed into mature piRNAs. How genomic regions that give rise to piRNA precursor transcripts are differentiated from the rest of the genome and how these transcripts are specifically channeled into the piRNA biogenesis pathway are not known. We found that transgenerationally inherited piRNAs provide the critical trigger for piRNA production from homologous genomic regions in the next generation by two different mechanisms. First, inherited piRNAs enhance processing of homologous transcripts into mature piRNAs by initiating the ping-pong cycle in the cytoplasm. Second, inherited piRNAs induce installment of the histone 3 Lys9 trimethylation (H3K9me3) mark on genomic piRNA cluster sequences. The heterochromatin protein 1 (HP1) homolog Rhino binds to the H3K9me3 mark through its chromodomain and is enriched over piRNA clusters. Rhino recruits the piRNA biogenesis factor Cutoff to piRNA clusters and is required for efficient transcription of piRNA precursors. We propose that transgenerationally inherited piRNAs act as an epigenetic memory for identification of substrates for piRNA biogenesis on two levels: by inducing a permissive chromatin environment for piRNA precursor synthesis and by enhancing processing of these precursors.

An intersectional investigation of Asian American men's muscularity-oriented disordered eating: Associations with gendered racism and masculine norms.

Grounded in an intersectional framework, the present study investigated the extent to which racism, gendered racism, and conformity to masculine norms are associated with Asian American men's muscularity-oriented disordered eating. The study also examined if ethnic identity moderated the association between both forms of racism and muscularity-oriented disordered eating. 220 Asian American men completed an online cross-sectional survey that contained the study questionnaires. Hierarchical regression analyses were conducted to examine the associations between our predictor variables and muscularity-oriented disordered eating. Gendered racism, conformity to the masculine norms of playboy, heterosexual presentation and self-reliance were positively associated with muscularity-oriented disordered eating, whereas conformity to power over women was negatively associated. Racism and the remaining masculine norms were not associated with muscularity-oriented disordered eating. Ethnic identity did not moderate the association between either form of racism and muscularity-oriented disordered eating. Given that gendered racism was positively associated with muscularity-oriented disordered eating whereas racism was not, researchers and practitioners may consider prioritizing intersectionality in their understanding of Asian American men's eating pathology. Results emphasize the importance of examining both race and gender in conceptualizing Asian American men's muscularity-oriented disordered eating.Data Availability Statement: Data for this study are available upon request from the first author.

A Retrospective Study of Tinea Capitis Management in General Pediatric Clinics and Pediatric Emergency Departments at 2 US Centers.

We examine management practices of tinea capitis at 2 US academic centers. The majority of providers treated tinea capitis with the oral antifungal agent griseofulvin and did not obtain a fungal culture. We recommend newer antifungal treatments such as terbinafine and fluconazole and obtaining a fungal culture for effective treatment.

Tinea capitis: advances and a needed paradigm shift.

PURPOSE OF REVIEW: Tinea capitis, a superficial infection of the scalp, is the most common pediatric dermatophyte fungal infection worldwide and is particularly common in the USA in low-income, low-resource settings. There are still gaps in knowledge and heterogeneities in practice in terms of diagnostic and management strategies. Furthermore, there are no clinical guidelines for management and treatment of tinea capitis in the USA. This review aims to summarize recent advances, recommend optimal management for the practicing pediatrician, and identify areas for future research for tinea capitis. RECENT FINDINGS: Trichophyton tonsurans infections are best treated with terbinafine and Microsporum canis infections are best treated with griseofulvin. Trichophyton tonsurans is the predominant cause of tinea capitis in the USA, although the main gold standard of treatment in the USA is griseofulvin. Dermatophyte antifungal resistance is an active area of investigation but seems to not be of current concern for tinea capitis in the USA. SUMMARY: We recommend all clinical providers ascertain the causative organism in fungal infection, either through fungal culture or newer methods which may become more readily available and cost-effective in the future, such as polymerase chain reaction assay. We also recommend terbinafine as first-line treatment of tinea capitis, with adjustment as necessary after species identification.