Chromatic periodic activity down to 120 megahertz in a fast radio burst.

Fast radio bursts (FRBs) are extragalactic astrophysical transients1 whose brightness requires emitters that are highly energetic yet compact enough to produce the short, millisecond-duration bursts. FRBs have thus far been detected at frequencies from 8 gigahertz (ref. 2) down to 300 megahertz (ref. 3), but lower-frequency emission has remained elusive. Some FRBs repeat4-6, and one of the most frequently detected, FRB 20180916B7, has a periodicity cycle of 16.35 days (ref. 8). Using simultaneous radio data spanning a wide range of wavelengths (a factor of more than 10), here we show that FRB 20180916B emits down to 120 megahertz, and that its activity window is frequency dependent (that is, chromatic). The window is both narrower and earlier at higher frequencies. Binary wind interaction models predict a wider window at higher frequencies, the opposite of our observations. Our full-cycle coverage shows that the 16.3-day periodicity is not aliased. We establish that low-frequency FRB emission can escape the local medium. For bursts of the same fluence, FRB 20180916B is more active below 200 megahertz than at 1.4 gigahertz. Combining our results with previous upper limits on the all-sky FRB rate at 150 megahertz, we find there are 3-450 FRBs in the sky per day above 50 Jy ms. Our chromatic results strongly disfavour scenarios in which absorption from strong stellar winds causes FRB periodicity. We demonstrate that some FRBs are found in 'clean' environments that do not absorb or scatter low-frequency radiation.

Author Correction: FOXA1 mutations alter pioneering activity, differentiation and prostate cancer phenotypes.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

FOXA1 mutations alter pioneering activity, differentiation and prostate cancer phenotypes.

Mutations in the transcription factor FOXA1 define a unique subset of prostate cancers but the functional consequences of these mutations and whether they confer gain or loss of function is unknown1-9. Here, by annotating the landscape of FOXA1 mutations from 3,086 human prostate cancers, we define two hotspots in the forkhead domain: Wing2 (around 50% of all mutations) and the highly conserved DNA-contact residue R219 (around 5% of all mutations). Wing2 mutations are detected in adenocarcinomas at all stages, whereas R219 mutations are enriched in metastatic tumours with neuroendocrine histology. Interrogation of the biological properties of wild-type FOXA1 and fourteen FOXA1 mutants reveals gain of function in mouse prostate organoid proliferation assays. Twelve of these mutants, as well as wild-type FOXA1, promoted an exaggerated pro-luminal differentiation program, whereas two different R219 mutants blocked luminal differentiation and activated a mesenchymal and neuroendocrine transcriptional program. Assay for transposase-accessible chromatin using sequencing (ATAC-seq) of wild-type FOXA1 and representative Wing2 and R219 mutants revealed marked, mutant-specific changes in open chromatin at thousands of genomic loci and exposed sites of FOXA1 binding and associated increases in gene expression. Of note, ATAC-seq peaks in cells expressing R219 mutants lacked the canonical core FOXA1-binding motifs (GTAAAC/T) but were enriched for a related, non-canonical motif (GTAAAG/A), which was preferentially activated by R219-mutant FOXA1 in reporter assays. Thus, FOXA1 mutations alter its pioneering function and perturb normal luminal epithelial differentiation programs, providing further support for the role of lineage plasticity in cancer progression.

Remote-Use Applications of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised Clinical Outcome Assessment Tool: A Scoping Review.

OBJECTIVES: In 2021, the US Congress passed the Accelerating Access to Critical Therapies for Amyotrophic Lateral Sclerosis Act. The law encourages development of "tools, methods, and processes" to improve clinical trial efficiency for neurodegenerative diseases. The Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) is an outcome measure administered during in-person clinic visits and used to support investigational studies for persons living with amyotrophic lateral sclerosis. Availability of a standardized, remote-use version of the ALSFRS-R may promote more inclusive, decentralized clinical trials. A scoping literature review was conducted to identify existing remote-use ALSFRS-R tools, synthesize feasibility and comparability of administration modes, and summarize barriers and facilitators to inform development of a standardized remote-use ALSFRS-R tool. METHODS: Included studies reported comparisons between remote and in-person, clinician-reported, ALSFRS-R administration and were published in English (2002-2022). References were identified by searching peer-reviewed and gray literature. Twelve studies met the inclusion criteria and were analyzed to compare findings within and across modes of administration. RESULTS: Remote modes of ALSFRS-R administration were categorized into 4 nonmutually exclusive categories: telephone (n = 6), videoconferencing (n = 3), computer or online platforms (n = 3), mobile applications and wearables (n = 2), and 1 unspecified telemedicine modality (n = 1). Studies comparing in-person to telephone or videoconferencing administration reported high ALSFRS-R rating correlations and nonsignificant between-mode differences. CONCLUSIONS: There is insufficient information in the ALSFRS-R literature to support remote clinician administration for collecting high quality data. Future research should engage persons living with amyotrophic lateral sclerosis, care partners, and providers to develop a standardized remote-use ALSFRS-R version.

Are parent-reported sleep logs essential? A comparison of three approaches to guide open source accelerometry-based nocturnal sleep processing in children.

We examined the comparability of children's nocturnal sleep estimates using accelerometry data, processed with and without a sleep log. In a secondary analysis, we evaluated factors associated with disagreement between processing approaches. Children (n = 722, age 5-12 years) wore a wrist-based accelerometer for 14 days during Autumn 2020, Spring 2021, and/or Summer 2021. Outcomes included sleep period, duration, wake after sleep onset (WASO), and timing (onset, midpoint, waketime). Parents completed surveys including children's nightly bed/wake time. Data were processed with parent-reported bed/wake time (sleep log), the Heuristic algorithm looking at Distribution of Change in Z-Angle (HDCZA) algorithm (no log), and an 8 p.m.-8 a.m. window (generic log) using the R-package 'GGIR' (version 2.6-4). Mean/absolute bias and limits of agreement were calculated and visualised with Bland-Altman plots. Associations between child, home, and survey characteristics and disagreement were examined with tobit regression. Just over half of nights demonstrated no difference in sleep period between sleep log and no log approaches. Among all nights, the sleep log approach produced longer sleep periods (9.3 min; absolute mean bias [AMB] = 28.0 min), shorter duration (1.4 min; AMB = 14.0 min), greater WASO (11.0 min; AMB = 15.4 min), and earlier onset (13.4 min; AMB = 17.4 min), midpoint (8.8 min; AMB = 15.3 min), and waketime (3.9 min; AMB = 14.8 min) than no log. Factors associated with discrepancies included smartphone ownership, bedroom screens, nontraditional parent work schedule, and completion on weekend/summer nights (range = 0.4-10.2 min). The generic log resulted in greater AMB among sleep outcomes. Small mean differences were observed between nights with and without a sleep log. Discrepancies existed on weekends, in summer, and for children with smartphones and screens in the bedroom.

Statewide Examination of Access to Cancer Surgery During the COVID-19 Pandemic.

INTRODUCTION: The COVID-19 pandemic caused interruptions in the delivery of medical care across a wide range of conditions including cancer. Trends in surgical treatment for cancer during the pandemic have not been well described. We sought to characterize associations between the pandemic and access to surgical treatment for breast, colorectal, and lung cancer in Illinois. METHODS: We performed a retrospective cohort study evaluating inpatient admissions at Illinois hospitals providing surgical care for lung cancer (n = 1913 cases, n = 64 hospitals), breast cancer (n = 910 cases, n = 108 hospitals), and colorectal cancer (n = 5339 cases, n = 144 hospitals). Using discharge data from the Illinois Health and Hospital Association's Comparative Health Care and Hospital Data Reporting Services database, average monthly surgical case volumes were compared from 2019 to 2020. We also compared rates of cancer surgery for each cancer type, by patient characteristics, and hospital type across the three time periods using Pearson chi-squared and ANOVA testing as appropriate. Three discrete time periods were considered: prepandemic (7-12/2019), primary pandemic (4-6/2020), and pandemic recovery (7-12/2020). Hospital characteristics evaluated included hospital type (academic, community, safety net), COVID-19 burden, and baseline cancer surgery volume. RESULTS: There were 2096 fewer operations performed for breast, colorectal, and lung cancer in 2020 than 2019 in Illinois, with the greatest reductions in cancer surgery volume occurring at the onset of the pandemic in April (colorectal, -48.3%; lung, -13.1%) and May (breast, -45.2%) of 2020. During the pandemic, breast (-14.6%) and colorectal (-13.8%) cancer surgery experienced reductions in volume whereas lung cancer operations were more common (+26.4%) compared to 2019. There were no significant differences noted in gender, race, ethnicity, or insurance status among patients receiving oncologic surgery during the primary pandemic or pandemic recovery periods. Academic hospitals, hospitals with larger numbers of COVID-19 admissions, and those with greater baseline cancer surgery volumes were associated with the greatest reduction in cancer surgery during the primary pandemic period (all cancer types, P < 0.01). During the recovery period, hospitals with greater baseline breast and lung cancer surgery volumes remained at reduced surgery volumes compared to their counterparts (P < 0.01). CONCLUSIONS: The COVID-19 pandemic was associated with significant reductions in breast and colorectal cancer operations in Illinois, while lung cancer operations remained relatively consistent. Overall, there was a net reduction in cancer surgery that was not made up during the recovery period. Academic hospitals, those caring for more COVID-19 patients, and those with greater baseline surgery volumes were most vulnerable to reduced surgery rates during peaks of the pandemic and to delays in addressing the backlog of cases.

Development of the UNC Perceived Message Effectiveness Scale for Youth.

PURPOSE: Tobacco prevention media campaigns are an important tool to address youth tobacco use. We developed a theory-based perceived message effectiveness (PME) Scale to use when vetting messages for campaigns. METHODS: Participants were a national sample of N=623 US adolescents (ages 13-17 years) recruited from a national probability-based panel. In an online experiment, we randomised adolescents to view tobacco prevention ads. All participants viewed an ad on smoking or vaping from the US Food and Drug Administration's The Real Cost campaign and a control video, in a random order. After ad exposure, we assessed PME using nine candidate items and constructs for convergent and criterion validity analyses. We used confirmatory factor analysis and examined information curves to select the scale items. RESULTS: A brief PME scale with three items (α=0.95) worked equally well for demographically diverse adolescents with different patterns of tobacco use. The Real Cost ads generated higher PME scores than the control videos for both vaping and smoking (convergent validity; p<0.05). Higher PME scores were associated with greater attention, fear, cognitive elaboration and anticipated social interactions (convergent validity; r=0.31-0.66), as well as more negative attitudes toward and lower susceptibility to vaping and smoking (criterion validity; r=-0.14 to -0.37). A single-item PME measure performed similarly to the three-item version. CONCLUSIONS: The University of North Carolina PME Scale for Youth is a reliable and valid measure of the potential effectiveness of vaping and smoking prevention ads. Employing PME scales during message development and selection may help youth tobacco prevention campaigns deploy more effective ads.

Risk factors associated with 31-day unplanned hospital readmission in newborns: a systematic review.

The purpose of this study is to synthesize evidence on risk factors associated with newborn 31-day unplanned hospital readmissions (UHRs). A systematic review was conducted searching CINAHL, EMBASE (Ovid), and MEDLINE from January 1st 2000 to 30th June 2021. Studies examining unplanned readmissions of newborns within 31 days of discharge following the initial hospitalization at the time of their birth were included. Characteristics of the included studies examined variables and statistically significant risk factors were extracted from the inclusion studies. Extracted risk factors could not be pooled statistically due to the heterogeneity of the included studies. Data were synthesized using content analysis and presented in narrative and tabular form. Twenty-eight studies met the eligibility criteria, and 17 significant risk factors were extracted from the included studies. The most frequently cited risk factors associated with newborn readmissions were gestational age, postnatal length of stay, neonatal comorbidity, and feeding methods. The most frequently cited maternal-related risk factors which contributed to newborn readmissions were parity, race/ethnicity, and complications in pregnancy and/or perinatal period. CONCLUSION: This systematic review identified a complex and diverse range of risk factors associated with 31-day UHR in newborn. Six of the 17 extracted risk factors were consistently cited by studies. Four factors were maternal (primiparous, mother being Asian, vaginal delivery, maternal complications), and two factors were neonatal (male infant and neonatal comorbidities). Implementation of evidence-based clinical practice guidelines for inpatient care and individualized hospital-to-home transition plans, including transition checklists and discharge readiness assessments, are recommended to reduce newborn UHRs. WHAT IS KNOWN: • Attempts have been made to identify risk factors associated with newborn UHRs; however, the results are inconsistent. WHAT IS NEW: • Six consistently cited risk factors related to newborn 31-day UHRs. Four maternal factors (primiparous, mother being Asian, vaginal delivery, maternal complications) and 2 neonatal factors (male infant and neonatal comorbidities). • The importance of discharge readiness assessment, including newborn clinical fitness for discharge and parental readiness for discharge. Future research is warranted to establish standardised maternal and newborn-related variables which healthcare providers can utilize to identify newborns at greater risk of UHRs and enable comparison of research findings.

Nutritional needs, resources, and barriers among unhoused adults cared for by a street medicine organization in Chicago, Illinois: a cross-sectional study.

BACKGROUND: Those experiencing houselessness rely on obtaining food from community organizers and donations. Simultaneously, the houseless face disproportionally high rates of medical conditions that may be affected by diet including diabetes, hypertension, and hyperlipidemia. There is limited literature on the resources and barriers of the houseless community regarding optimal nutrition from an actionable perspective. Further, less data is available on how street medicine organizations may best impact the nutrition of the unhoused they serve. Elucidating this information will inform how organizational efforts may best support the nutrition of the houseless community. METHODS: In partnership with the medical student-run organization, Chicago Street Medicine, at Northwestern University Feinberg School of Medicine, twenty adults experiencing houselessness in Chicago, Illinois participated in the cross-sectional study. A 10-item survey was verbally administered to characterize the participants' daily food intake, food sources, barriers, resources, and nutritional preferences and needs. All data was directly transcribed into REDCap. Descriptive statistics were generated. RESULTS: Individuals consumed a median of 2 snacks and meals per day (IQR: 1-3). No participant consumed adequate servings of every food group, with only one participant meeting the dietary intake requirements for one food group. Participants most often received their food from donations (n = 15), purchasing themselves (n = 11), food pantries (n = 4), and shelters (n = 3). Eleven of nineteen participants endorsed dental concerns as a major barrier to consuming certain foods. Twelve participants had access to a can opener and twelve could heat their meals on a stove or microwave. Seven had access to kitchen facilities where they may prepare a meal. Approximately half of participants had been counseled by a physician to maintain a particular diet, with most related to reducing sugar intake. CONCLUSION: Most houseless participants were unable to acquire a balanced diet and often relied on organizational efforts to eat. Organizations should consider the chronic health conditions, dentition needs, and physical resources and barriers to optimal nutrition when obtaining food to distribute to the unhoused.

Pockets of Peace: A mixed methods, exploratory study of neighborhoods resilient to juvenile violence.

Social science research has focused on hot spots of adolescent violence in marginalized urban neighborhoods for nearly a century. In contrast, in this study, we explore under-resourced urban areas that do not experience high rates of adolescent violence: "pockets of peace." We use a mixed-method approach to identify the sociodemographic, geographic, and criminological commonalities and differences between pockets of peace and other areas of concentrated disadvantage dealing with high rates of adolescent violence in Indianapolis, IN. More than one out of every ten of Indianapolis' areas of concentrated disadvantage meet the criteria to be labeled "pockets of peace." Quantitative data indicate that these areas have fewer prosocial institutions and experience lower homeownership rates than comparison under-resourced areas, and qualitative data point toward rental stability and residential longevity as potentially salient social factors within these contexts. As an alternative to using statistics to control for the context of structural disadvantage, studying pockets of peace and other "cold-spots" of adolescent violence presents an opportunity to understand community-level resilience within the real, lived context of structural disadvantage.

Association of body mass index and inflammatory dietary pattern with breast cancer pathologic and genomic immunophenotype in the nurses' health study.

BACKGROUND: Breast tumor immune infiltration is clearly associated with improved treatment response and outcomes in breast cancer. However, modifiable patient factors associated with breast cancer immune infiltrates are poorly understood. The Nurses' Health Study (NHS) offers a unique cohort to study immune gene expression in tumor and adjacent normal breast tissue, immune cell-specific immunohistochemistry (IHC), and patient exposures. We evaluated the association of body mass index (BMI) change since age 18, physical activity, and the empirical dietary inflammatory pattern (EDIP) score, all implicated in systemic inflammation, with immune cell-specific expression scores. METHODS: This population-based, prospective observational study evaluated 882 NHS and NHSII participants diagnosed with invasive breast cancer with detailed exposure and gene expression data. Of these, 262 women (training cohort) had breast tumor IHC for four classic immune cell markers (CD8, CD4, CD20, and CD163). Four immune cell-specific scores were derived via lasso regression using 105 published immune expression signatures' association with IHC. In the remaining 620 patient evaluation cohort, we evaluated association of each immune cell-specific score as outcomes, with BMI change since age 18, physical activity, and EDIP score as predictors, using multivariable-adjusted linear regression. RESULTS: Among women with paired expression/IHC data from breast tumor tissue, we identified robust correlation between novel immune cell-specific expression scores and IHC. BMI change since age 18 was positively associated with CD4+ (ß = 0.16; p = 0.009), and CD163 novel immune scores (ß = 0.14; p = 0.04) in multivariable analyses. In other words, for each 10 unit (kg/m2) increase in BMI, the percentage of cells positive for CD4 and CD163 increased 1.6% and 1.4%, respectively. Neither physical activity nor EDIP was significantly associated with any immune cell-specific expression score in multivariable analyses. CONCLUSIONS: BMI change since age 18 was positively associated with novel CD4+ and CD163+ cell scores in breast cancer, supporting further study of the effect of modifiable factors like weight gain on the immune microenvironment.

Sleep onset, duration, or regularity: which matters most for child adiposity outcomes?

BACKGROUND/OBJECTIVES: Sleep measures, such as duration and onset timing, are associated with adiposity outcomes among children. Recent research among adults has considered variability in sleep and wake onset times, with the Sleep Regularity Index (SRI) as a comprehensive metric to measure shifts in sleep and wake onset times between days. However, little research has examined regularity and adiposity outcomes among children. This study examined the associations of three sleep measures (i.e., sleep duration, sleep onset time, and SRI) with three measures of adiposity (i.e., body mass index [BMI], waist circumference, and waist-to-height ratio [WHtR]) in a pediatric sample. SUBJECTS/METHODS: Children (ages 4-13 years) who were part of the U.S. Newborn Epigenetic STudy (NEST) participated. Children (N = 144) wore an ActiGraph for 1 week. Sleep measures were estimated from actigraphy data. Weight, height, and waist circumference were measured by trained researchers. BMI and WHtR was calculated with the objectively measured waist and height values. Multiple linear regression models examined associations between child sleep and adiposity outcomes, controlling for race/ethnicity, child sex, age, mothers' BMI and sleep duration. RESULTS: When considering sleep onset timing and duration, along with demographic covariates, sleep onset timing was not significantly associated with any of the three adiposity measures, but a longer duration was significantly associated with a lower BMI Z-score (ß = -0.29, p < 0.001), waist circumference (ß = -0.31, p < 0.001), and WHtR (ß = -0.38, p < 0.001). When considering SRI and duration, duration remained significantly associated with the adiposity measures. The SRI and adiposity associations were in the expected direction, but were non-significant, except the SRI and WHtR association (ß = -0.16, p = 0.077) was marginally non-significant. CONCLUSIONS: Sleep duration was consistently associated with adiposity measures in children 4-13 years of age. Pediatric sleep interventions should focus first on elongating nighttime sleep duration, and examine if this improves child adiposity outcomes.

Adolescents' Understanding of Smoking and Vaping Risk Language: Cognitive Interviews to Inform Scale Development.

INTRODUCTION: Perceived message effectiveness (PME) is a common metric to understand receptivity to tobacco prevention messages, yet most measures have been developed with adults. We examined adolescents' interpretation of language within candidate items for a new youth-targeted PME measure using cognitive interviewing. We sought to understand the meaning adolescents assigned to our candidate PME items to improve item wording. AIMS AND METHODS: Participants were 20 adolescents, ages 13-17 years from the United States. Cognitive interviews used a structured guide to elicit feedback on comprehension, answer retrieval, and language regarding a set of Reasoned Action Approach-based survey items that assessed the PME of smoking and vaping prevention ads. We employed thematic analysis to synthesize findings from the interviews. RESULTS: Interviews identified three main issues related to survey items: ambiguity of language, word choice (risk and other terminology), and survey item phrasing. Adolescents preferred direct, definitive language over more ambiguous phrasing which they saw as less serious (eg, "will" instead of "could"). For risk terminology, they preferred terms such as "harmful" and "dangerous" over "risky," which was viewed as easy to discount. The term "negative effects" was interpreted as encompassing a broader set of tobacco harms than "health effects." Adolescents said that the term "vape" was preferable to "e-cigarette," and identified ways to simplify item wording for greater clarity. CONCLUSIONS: Tobacco risk terms that appear similar differ in meaning to adolescents, and more direct and unambiguous language is preferred. Our findings informed changes to the PME scale items to improve clarity and reduce measurement error. IMPLICATIONS: This study adds to the literature on how adolescents interpret tobacco prevention language. Adolescents may interpret terminology differently than adults, which could lead to ambiguity in meaning and thus measurement error. Through cognitive interviewing, we identified and improved the language in a youth-focused PME measure for tobacco and vaping prevention.

Heart Failure in Complex Congenital Heart Disease of the Adult.

PURPOSE OF REVIEW: Adult congenital heart disease (ACHD) patients have demonstrated improved survival, especially those with severely complex disease, mainly single-ventricle/Fontan physiology and those with a systemic right ventricle. We describe the heart failure phenotypes of complex CHD, reversible causes for heart failure, and considerations for advanced therapy. RECENT FINDINGS: While initially marketed for application to patients with acquired causes for heart failure, newer devices and technologies have started to be used in the ACHD population. After reversible causes for heart failure in CHD are addressed, it is reasonable to consider use of new device-based technologies and orthotopic heart transplant (OHT) for end-stage disease. New heart failure technology and organ transplant should carefully be considered and applied in complex ACHD, where there may be significant improvement in morbidity and mortality.

How Emotional Shifts Effect Youth Perceptions of Opioid Risk and Efficacy: Testing a Know the Truth Campaign Narrative.

Integrating the extended parallel process model (EPPM) and the emotional flow hypothesis, we tested the persuasive effect of emotional shifts during exposure to a Know the Truth anti-opioid campaign narrative in a sample of middle-school students (n = 480). Testing two emotional flow sequences (threat to efficacy and efficacy to threat) of the Know the Truth narrative against a static (threat-only) emotional condition, we found that youth exposed to any emotional flow narrative reported higher levels of hope and lower levels of fear than those exposed to a threat-only narrative. We also found that a threat to efficacy narrative elicited higher levels of self-efficacy than an efficacy to threat emotional flow condition, suggesting that the emotional sequence influences self-efficacy, a well-established predictor of health behavior change. We conclude that the traditional threat to efficacy emotional flow may be superior to its inverse (efficacy to threat) when communicating with young people about opioid addiction. Implications for message design are discussed.

Psychosocial Needs of Gynecological Cancer Survivors: Mixed Methods Study.

BACKGROUND: Internet and social media platforms offer insights into the lived experiences of survivors of cancer and their caregivers; however, the volume of narrative data available is often cumbersome for thorough analysis. Survivors of gynecological cancer have unique needs, such as those related to a genetic predisposition to future cancers, impact of cancer on sexual health, the advanced stage at which many are diagnosed, and the influx of new therapeutic approaches. OBJECTIVE: This study aimed to present a unique methodology to leverage large amounts of data from internet-based platforms for mixed methods analysis. We analyzed discussion board posts made by survivors of gynecological cancer on the American Cancer Society website with a particular interest in evaluating the psychosocial aspects of survivorship. METHODS: All posts from the ovarian, uterine, and gynecological cancers (other than ovarian and uterine) discussion boards on the American Cancer Society Cancer Survivors Network were included. Posts were web scraped using Python and organized by psychosocial themes described in the Quality of Cancer Survivorship Care Framework. Keywords related to each theme were generated and verified. Keywords identified posts related to the predetermined psychosocial themes. Quantitative analysis was completed using Python and R Foundation for Statistical Computing packages. Qualitative analysis was completed on a subset of posts as a proof of concept. Themes discovered through latent Dirichlet allocation (LDA), an unsupervised topic modeling technique, were assessed and compared with the predetermined themes of interest. RESULTS: A total of 125,498 posts made by 6436 survivors of gynecological cancer and caregivers between July 2000 and February 2020 were evaluated. Of the 125,489 posts, 23,458 (18.69%) were related to the psychosocial experience of cancer and were included in the mixed methods psychosocial analysis. Quantitative analysis (23,458 posts) revealed that survivors across all gynecological cancer discussion boards most frequently discussed the role of friends and family in care, as well as fatigue, the effect of cancer on interpersonal relationships, and health insurance status. Words related to psychosocial aspects of survivorship most often used in posts included "family," "hope," and "help." Qualitative analysis (20 of the 23,458 posts) similarly demonstrated that survivors frequently discussed coping strategies, distress and worry, the role of family and caregivers in their cancer care, and the toll of managing financial and insurance concerns. Using LDA, we discovered 8 themes, none of which were directly related to psychosocial aspects of survivorship. Of the 56 keywords identified by LDA, 2 (4%), "sleep" and "work," were included in the keyword list that we independently devised. CONCLUSIONS: Web-based discussion platforms offer a great opportunity to learn about patient experiences of survivorship. Our novel methodology expedites the quantitative and qualitative analyses of such robust data, which may be used for additional patient populations.

Narratives of prevention and redemption in opioid overdose obituaries.

Obituaries of people who died from an opioid overdose represent a new territory for understanding cultural narratives of the US opioid epidemic. Drawing on textual analysis of 30 opioid overdose obituaries published on Legacy.com between 2015 and 2020, we describe a prototypical narrative conveyed through opioid overdose obituaries, which renders symbolic meaning through the voices of the bereaved. Obituary authors reimagine their subjects as tragic heroes and reconstitute opioid addiction as a curse, plight or affliction that befalls its victims. Many of these obituaries invoke the language of public health, calling for reform, action or general awareness so other families might avoid the havoc and heartbreak of opioid addiction. We argue that obituaries contribute to broader cultural narratives of opioid addiction by reproducing tragic storylines, vindicating and humanising the deceased, framing opioid addiction as a societal, rather than individual, problem, and medicalising addiction as a brain disease beyond a person's control. Obituary texts thus intertwine a personal story with a broader societal health crisis, transforming stories of the deceased into cautionary tales and public health warnings.

Experiences and Situations of Shame among Food-insecure Adolescents in South Carolina and Oregon.

Shame experienced with food insecurity and participating in food assistance may affect adolescents. We investigated adolescents' experiences of shame related to food insecurity and situations for these experiences in an ethnically diverse sample of 40 adolescents aged 9-15 years from South Carolina and Oregon. In-depth interviews were recorded, transcribed, coded, and analyzed. Participants described feelings of sadness, anger, and internalized shame with food insecurity. Salient situations were participating in food assistance, seeking food assistance from others or community services, and social encounters at school among peers. Adolescents felt shame knowing that peers were aware of their food insecurity and about them participating in food assistance through school.

Genomic features of rapid versus late relapse in triple negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is a heterogeneous disease and we have previously shown that rapid relapse of TNBC is associated with distinct sociodemographic features. We hypothesized that rapid versus late relapse in TNBC is also defined by distinct clinical and genomic features of primary tumors. METHODS: Using three publicly-available datasets, we identified 453 patients diagnosed with primary TNBC with adequate follow-up to be characterized as 'rapid relapse' (rrTNBC; distant relapse or death ≤2 years of diagnosis), 'late relapse' (lrTNBC; > 2 years) or 'no relapse' (nrTNBC: > 5 years no relapse/death). We explored basic clinical and primary tumor multi-omic data, including whole transcriptome (n = 453), and whole genome copy number and mutation data for 171 cancer-related genes (n = 317). Association of rapid relapse with clinical and genomic features were assessed using Pearson chi-squared tests, t-tests, ANOVA, and Fisher exact tests. We evaluated logistic regression models of clinical features with subtype versus two models that integrated significant genomic features. RESULTS: Relative to nrTNBC, both rrTNBC and lrTNBC had significantly lower immune signatures and immune signatures were highly correlated to anti-tumor CD8 T-cell, M1 macrophage, and gamma-delta T-cell CIBERSORT inferred immune subsets. Intriguingly, lrTNBCs were enriched for luminal signatures. There was no difference in tumor mutation burden or percent genome altered across groups. Logistic regression mModels that incorporate genomic features significantly outperformed standard clinical/subtype models in training (n = 63 patients), testing (n = 63) and independent validation (n = 34) cohorts, although performance of all models were overall modest. CONCLUSIONS: We identify clinical and genomic features associated with rapid relapse TNBC for further study of this aggressive TNBC subset.

Functions of the COPII gene paralogs SEC23A and SEC23B are interchangeable in vivo.

Approximately one-third of the mammalian proteome is transported from the endoplasmic reticulum-to-Golgi via COPII-coated vesicles. SEC23, a core component of coat protein-complex II (COPII), is encoded by two paralogous genes in vertebrates (Sec23a and Sec23b). In humans, SEC23B deficiency results in congenital dyserythropoietic anemia type-II (CDAII), while SEC23A deficiency results in a skeletal phenotype (with normal red blood cells). These distinct clinical disorders, together with previous biochemical studies, suggest unique functions for SEC23A and SEC23B. Here we show indistinguishable intracellular protein interactomes for human SEC23A and SEC23B, complementation of yeast Sec23 by both human and murine SEC23A/B, and rescue of the lethality of sec23b deficiency in zebrafish by a sec23a-expressing transgene. We next demonstrate that a Sec23a coding sequence inserted into the murine Sec23b locus completely rescues the lethal SEC23B-deficient pancreatic phenotype. We show that SEC23B is the predominantly expressed paralog in human bone marrow, but not in the mouse, with the reciprocal pattern observed in the pancreas. Taken together, these data demonstrate an equivalent function for SEC23A/B, with evolutionary shifts in the transcription program likely accounting for the distinct phenotypes of SEC23A/B deficiency within and across species, a paradigm potentially applicable to other sets of paralogous genes. These findings also suggest that enhanced erythroid expression of the normal SEC23A gene could offer an effective therapeutic approach for CDAII patients.