Differences in elementary-age children's accelerometer - measured physical activity between school and summer: three-year findings from the What's UP (Undermining Prevention) with summer observational cohort study.

BACKGROUND: Among elementary-aged children (5-12yrs), summer vacation is associated with accelerated gains in Body Mass Index (BMI). A key behavioral driver of BMI gain is a lack of physical activity (PA). Previous studies indicate PA decreases during summer, compared to the school year but whether this difference is consistent among boys and girls, across age, and by income status remains unclear. This study examined differences in school and summer movement behaviors in a diverse cohort of children across three years. METHODS: Children (N = 1,203, age range 5-14 years, 48% girls) wore wrist-placed accelerometers for a 14-day wear-period during school (April/May) and summer (July) in 2021 to 2023, for a total of 6 timepoints. Mixed-effects models examined changes in school vs. summer movement behaviors (moderate-to-vigorous physical activity [MVPA], sedentary) for boys and girls, separately, and by age and household income groups (low, middle, and upper based on income-to-poverty ratio). RESULTS: Children provided a total of 35,435 valid days of accelerometry. Overall, boys (+ 9.1 min/day, 95CI 8.1 to 10.2) and girls (+ 6.2 min/day, 95CI 5.4 to 7.0) accumulated more MVPA during school compared to summer. Boys accumulated less time sedentary (-9.9 min/day, 95CI -13.0 to -6.9) during school, while there was no difference in sedentary time (-2.7 min/day, 95CI -5.7 to 0.4) for girls. Different patterns emerged across ages and income groups. Accumulation of MVPA was consistently greater during school compared to summer across ages and income groups. Generally, the difference between school and summer widened with increasing age, except for girls from middle-income households. Accumulation of sedentary time was higher during school for younger children (5-9yrs), whereas for older children (10-14yrs), sedentary time was greater during summer for the middle- and upper-income groups. For boys from low-income households and girls from middle-income households, sedentary time was consistently greater during summer compared to school across ages. CONCLUSIONS: Children are less active and more sedentary during summer compared to school, which may contribute to accelerated BMI gain. However, this differs by biological sex, age, and income. These findings highlight the complex factors influencing movement behaviors between school and summer.

Comprehensive Target Engagement by the EZH2 Inhibitor Tulmimetostat Allows for Targeting of ARID1A Mutant Cancers.

Recurrent somatic mutations in the BRG1/BRM-associated factor (BAF) chromatin remodeling complex subunit ARID1A occur frequently in advanced urothelial, endometrial, and ovarian clear cell carcinomas, creating an alternative chromatin state that may be exploited therapeutically. The histone methyltransferase EZH2 has been previously identified as targetable vulnerability in the context of ARID1A mutations. In this study, we describe the discovery of tulmimetostat, an orally available, clinical stage EZH2 inhibitor, and it elucidates the aspects of its application potential in ARID1A mutant tumors. Tulmimetostat administration achieved efficacy in multiple ARID1A mutant bladder, ovarian, and endometrial tumor models and improved cisplatin response in chemotherapy-resistant models. Consistent with its comprehensive and durable level of target coverage, tulmimetostat demonstrated greater efficacy than other PRC2-targeted inhibitors at comparable or lower exposures in a bladder cancer xenograft mouse model. Tulmimetostat mediated extensive changes in gene expression, in addition to a profound reduction in global H3K27me3 levels in tumors. Phase I clinical pharmacokinetic and pharmacodynamic data indicated that tulmimetostat exhibits durable exposure and profound target engagement. Importantly, a tulmimetostat controlled gene expression signature identified in whole blood from a cohort of 32 patients with cancer correlated with tulmimetostat exposure, representing a pharmacodynamic marker for the assessment of target coverage for PRC2-targeted agents in the clinic. Collectively, these data suggest that tulmimetostat has the potential to achieve clinical benefit in solid tumors as a monotherapy but also in combination with chemotherapeutic agents, and may be beneficial in various indications with recurrent ARID1A mutations. Significance: The EZH2 inhibitor tulmimetostat achieves comprehensive target inhibition in ARID1A mutant solid tumor models and cancer patients that can be assessed with a pharmacodynamic gene signature in peripheral blood.

Implementing cone-beam computed tomography-guided online adaptive radiotherapy in cervical cancer.

Background and purpose: Adaptive radiotherapy (ART) in locally advanced cervical cancer (LACC) has shown promising outcomes. This study investigated the feasibility of cone-beam computed tomography (CBCT)-guided online ART (oART) for the treatment of LACC. Material and methods: The quality of the automated radiotherapy treatment plans and artificial intelligence (AI)-driven contour delineation for LACC on a novel CBCT-guided oART system were assessed. Dosimetric analysis of 200 simulated oART sessions were compared with standard treatment. Feasibility of oART was assessed from the delivery of 132 oART fractions for the first five clinical LACC patients. The simulated and live oART sessions compared a fixed planning target volume (PTV) margin of 1.5 cm around the uterus-cervix clinical target volume (CTV) with an internal target volume-based approach. Workflow timing measurements were recorded. Results: The automatically-generated 12-field intensity-modulated radiotherapy plans were comparable to manually generated plans. The AI-driven organ-at-risk (OAR) contouring was acceptable requiring, on average, 12.3 min to edit, with the bowel performing least well and rated as unacceptable in 16 % of cases. The treated patients demonstrated a mean PTV D98% (+/-SD) of 96.7 (+/- 0.2)% for the adapted plans and 94.9 (+/- 3.7)% for the non-adapted scheduled plans (p<10-5). The D2cc (+/-SD) for the bowel, bladder and rectum were reduced by 0.07 (+/- 0.03)Gy, 0.04 (+/-0.05)Gy and 0.04 (+/-0.03)Gy per fraction respectively with the adapted plan (p <10-5). In the live.setting, the mean oART session (+/-SD) from CBCT acquisition to beam-on was 29 +/- 5 (range 21-44) minutes. Conclusion: CBCT-guided oART was shown to be feasible with dosimetric benefits for patients with LACC. Further work to analyse potential reductions in PTV margins is ongoing.

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.

Patient Understanding of Tumor Genomic Testing: A Quality Improvement Effort.

PURPOSE: Tumor genomic testing (TGT) has become increasingly adopted as part of standard cancer care for many cancers. Despite national guidelines around patient education before TGT, available evidence suggests that most patients' understanding of genomics remains limited, particularly lower-income and minority patients, and most patients are not informed regarding potential incidental germline findings. METHODS: To investigate and address limitations in patient understanding of TGT results, a Plan-Do-Study-Act (PDSA) approach is being used to assess needs, identify opportunities for improvement, and implement approaches to optimize patient education. We reviewed published guidelines related to pre-TGT provider-patient education and to identify key points (Plan). A provider quality improvement survey was completed (Do), which highlighted inconsistency in pre-TGT discussion practice across providers and minimal discussion with patients regarding the possibility of incidental germline findings. RESULTS: Patient focus groups and interviews (N = 12 patients) were completed with coding of each transcript (Study), which revealed themes including trouble differentiating TGT from other forms of testing, yet understanding that results could tailor therapy. The integration of data across this initial PDSA cycle identified consistent themes and opportunities, which were incorporated into a patient-directed, concise animated video for pre-TGT education (Act), which will form the foundation of a subsequent PDSA cycle. The video addresses how TGT may/may not inform treatment, the process for TGT using existing tissue or liquid biopsy, insurance coverage, and the potential need for germline genetics follow-up because of incidental findings. CONCLUSION: This PDSA cycle reveals key gaps and opportunities for improvement in patient education before TGT.

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.

Gender Disparities and Differences Among Urologists Included in Top Doctor Lists.

OBJECTIVE: To understand gender trends among urologists included in "Top Doctor" lists as more women practice urology, we (1) Evaluated whether Top Doctor lists reflect a contemporary distribution of urologists by gender; (2) Describe regional differences in gender composition of lists; (3) Report similarities and differences among men and women Top Doctors. METHODS: All urologists in regional Top Doctor Castle Connolly lists published in magazines between January 1, 2020 and June 22, 2021 were included. Physician attributes were abstracted. American Urological Association (AUA) census data was used to compare the number of men and women Top Doctor urologists to the number of practicing men and women urologists within each list's zip codes. Log odds ratios (OR) and (95% confidence intervals) were used to compare likelihood of list inclusion by gender overall and by region. RESULTS: Four hundred and ninety-four Top Doctor urologists from 25 lists were analyzed, of which 42 (8.50%) were women. Women urologists comprised 0%-27.8% of each list, with 7 lists (28.0%) including zero women urologists. Using AUA census data, OR for list inclusion of men urologists compared to women was 1.31 (1.01, 1.70) overall, with OR = 0.78 (0.36, 1.72) in the West, OR = 1.39 (1.03, 1.89) South, OR = 1.46 (0.8, 2.67) Northeast, OR = 1.90 (0.50, 7.18) Midwest. Women top urologists completed fellowship more often than men (66.7%, 55.1%) and were significantly more likely to complete female pelvic medicine and reconstructive surgery (FPMRS) fellowship (P <.001). CONCLUSION: Men urologists were significantly more likely to be included in Top Doctor lists than women urologists. Top women urologists were significantly more likely to complete FPMRS fellowship.

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.

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.

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.

Using multi-centre data to train and validate a knowledge-based model for planning radiotherapy of the head and neck.

Background and purpose: Knowledge-based radiotherapy planning models have been shown to reduce healthy tissue dose and optimisation times, with larger training databases delivering greater robustness. We propose a method of combining knowledge-based models from multiple centres to create a 'super-model' using their collective patient libraries, thereby increasing the breadth of training knowledge. Materials and methods: A head and neck super-model containing 207 patient datasets was created by merging the data libraries of three centres. Validation was performed on 30 independent datasets during which optimiser parameters were tuned to deliver the optimal set of model template objectives. The super-model was tested on a further 40 unseen patients from four radiotherapy centres, including one centre external to the training process. The generated plans were assessed using established plan evaluation criteria. Results: The super-model generated plans that surpassed the dose objectives for all patients with single optimisations in an average time of 10 min. Healthy tissue sparing was significantly improved over manual planning, with dose reductions to parotid of 4.7 ± 2.1 Gy, spinal cord of 3.3 ± 0.9 Gy and brainstem of 2.9 ± 1.7 Gy. Target coverage met the established constraints but was marginally reduced compared with clinical plans. Conclusions: Three centres successfully merged patient libraries to create a super-model capable of generating plans that met plan evaluation criteria for head and neck patients with improvements in healthy tissue sparing. The findings indicate that the super-model could improve head and neck planning quality, efficiency and consistency across radiotherapy centres.

Impact of the COVID-19 pandemic on elementary schoolers' physical activity, sleep, screen time and diet: A quasi-experimental interrupted time series study.

BACKGROUND: COVID-19 school closures pose a threat to children's wellbeing, but no COVID-19-related studies have assessed children's behaviours over multiple years . OBJECTIVE: To examine children's obesogenic behaviours during spring and summer of the COVID-19 pandemic compared to previous data collected from the same children during the same calendar period in the 2 years prior. METHODS: Physical activity and sleep data were collected via Fitbit Charge-2 in 231 children (7-12 years) over 6 weeks during spring and summer over 3 years. Parents reported their child's screen time and dietary intake via a survey on 2-3 random days/week. RESULTS: Children's behaviours worsened at a greater rate following the pandemic onset compared to pre-pandemic trends. During pandemic spring, sedentary behaviour increased (+79 min; 95% CI = 60.6, 97.1) and MVPA decreased (-10 min, 95% CI = -18.2, -1.1) compared to change in previous springs (2018-2019). Sleep timing shifted later (+124 min; 95% CI = 112.9, 135.5). Screen time (+97 min, 95% CI = 79.0, 115.4) and dietary intake increased (healthy: +0.3 foods, 95% CI = 0.2, 0.5; unhealthy: +1.2 foods, 95% CI = 1.0, 1.5). Similar patterns were observed during summer. CONCLUSIONS: Compared to pre-pandemic measures, children's PA, sedentary behaviour, sleep, screen time, and diet were adversely altered during the COVID-19 pandemic. This may ultimately exacerbate childhood obesity.

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.

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.

Pediatric Surgery and School Nurse Attitudes Regarding Children with Obesity.

PURPOSE: Weight bias towards individuals with obesity exists among medical professionals; yet, there is less evidence of the extent to which weight biases exist in different types of nursing professions. This study aimed to describe pediatric surgery and school nurses' weight biases towards children with obesity and examine factors associated with weight biases. DESIGN AND METHODS: Pediatric surgery (n = 108) and school nurses (n = 177) completed a single online survey that assessed their attitudes towards weight regarding children with obesity. Responses were categorized as % agreement (responded "agree" or "strongly agree" to a given statement). Nurses also reported % time spent working with children who had obesity. RESULTS: Almost all nurses (>93%) agreed it was important to treat patients with obesity with compassion and respect. However, many nurses endorsed statements stating that patients with obesity are often non-compliant with treatment recommendations (47%) and can be difficult to deal with (35%). Only about half of school nurses (53%) and surgical nurses (56%) felt professionally prepared to effectively treat patients with obesity. Nurses commonly reported hearing/witnessing other professionals in their field make negative comments (69%) or convey negative stereotypes (55%) about patients with obesity. School nurses who spent a greater % of time working with children with overweight had more positive weight attitudes (p = 0.04). CONCLUSIONS: Negative attitudes towards patients with obesity were relatively prevalent in this population of pediatric surgery and school nurses. PRACTICE IMPLICATIONS: There is a need for more educational opportunities, professional trainings, and policy initiatives to reduce weight bias among nurses.

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.

Cognitive and behavioral outcome of stereotactic laser amydalohippocampotomy in a pediatric setting.

We present neuropsychological and functional outcome data in a teenager undergoing stereotactic laser amygdalohippocampotomy (SLAH) who had drug-resistant mesial temporal lobe epilepsy due to left hippocampal sclerosis. Given strong baseline cognitive performance, there was concern for post-operative declines in language and verbal memory were this patient to undergo open resection. She was evaluated pre- and post-ablation with clinical and experimental neuropsychological measures including semantic memory, category-specific object/face recognition and naming, spatial learning, and socio-emotional processing. The patient became seizure-free following SLAH and experienced significant improvements in school performance and social engagement. She experienced improvement in recognition and naming of multiple object categories, memory functions, and verbal fluency. In contrast, the patient declined significantly in her ability to recognize emotional tone from facial expressions, a socio-emotional process that had been normal prior to surgery. We believe this decline was related to surgical disruption of the limbic system, an area highly involved in emotional processing, and suspect such deficits are an under-assessed and unrecognized risk for all surgeries involving the amygdalohippocampal complex and broader limbic system regions. We hope this positive SLAH outcome will serve as impetus for group level research to establish its safety and efficacy in the pediatric setting.

Metastatic breast cancer patient perceptions of somatic tumor genomic testing.

BACKGROUND: To assess metastatic breast cancer (MBC) patient psychological factors, perceptions, and comprehension of tumor genomic testing. METHODS: In a prospective, single institution, single-arm trial, patients with MBC underwent next-generation sequencing at study entry with sequencing results released at progression. Patients who completed surveys before undergoing sequencing were included in the present secondary analysis (n = 58). We administered four validated psychosocial measures: Center for Epidemiologic Studies Depression Scale, Beck Anxiety Inventory, Trust in Physician Scale, and Communication and Attitudinal Self-Efficacy scale for Cancer. Genetic comprehension was assessed using 7-question objective and 6-question subjective measures. Longitudinal data were assessed (n = 40) using paired Wilcoxon signed rank and McNemar's test of agreement. RESULTS: There were no significant differences between the beginning and end of study in depression, anxiety, physician trust, or self-efficacy (median time on study: 7.6 months). Depression and anxiety were positively associated with each other and both negatively associated with self-efficacy. Self-efficacy decreased from pre- to post-genomic testing (p = 0.05). Objective genetics comprehension did not significantly change from pre- to post-genomic testing, but patients expressed increased confidence in their ability to teach others about genetics (p = 0.04). Objective comprehension was significantly lower in non-white patients (p = 0.02) and patients with lower income (p = 0.04). CONCLUSIONS: This is the only study, to our knowledge, to longitudinally evaluate multiple psychological metrics in MBC as patients undergo tumor genomic testing. Overall, psychological dimensions remained stable over the duration of tumor genomic testing. Among patients with MBC, depression and anxiety metrics were negatively correlated with patient self-efficacy. Patients undergoing somatic genomic testing had limited genomic knowledge, which varied by demographic groups and may warrant additional educational intervention. CLINICAL TRIAL INFORMATION: NCT01987726, registered November 13, 2013.

Aggressive Subsets of Metastatic Triple Negative Breast Cancer.

BACKGROUND: Relative to other metastatic breast cancer subtypes, metastatic triple-negative breast cancer (mTNBC) has a shorter duration of response to therapy and worse overall survival. Among patients with mTNBC, it is hypothesized that inflammatory breast cancer (IBC) and young women have particularly aggressive phenotypes. We investigated clinical and cell-free DNA (cfDNA) characteristics of inflammatory-mTNBC and young-mTNBC. PATIENTS AND METHODS: We evaluated 158 patients with mTNBC who were stratified into 3 groups: (1) IBC; (2) patients aged 45 years or younger at primary diagnosis without IBC (non-IBC young); and (3) patients over age 45 at diagnosis without IBC. We evaluated clinicopathologic characteristics, sites of metastasis, survival outcomes, and the fraction of DNA in circulation derived from tumor (TFx). RESULTS: Analysis of metastatic sites revealed that young patients without IBC had the most frequent lung metastases (P = .002). cfDNA analyses of first sample showed that TFx was highest in the non-IBC young group but not elevated in the IBC group (analysis of variance P = .056 for first TFx). Individually, median overall survival from metastatic diagnosis for the IBC group was 15.2 months; for the non-IBC young group, 21.2 months, and for the non-IBC over 45 group, 31.2 months. Patients with IBC and young patients without IBC had worse prognosis relative to patients over 45 without IBC (log-rank P = .023). CONCLUSIONS: Among patients with mTNBC in this single-institution cohort, patients with IBC and young patients without IBC had significantly worse overall survival compared with patients over 45 without IBC. Young patients without IBC had significantly higher cfDNA TFx, whereas patients with IBC did not have elevated TFx despite a poor prognosis. These findings demonstrate that further analyses of mTNBC subsets are warranted.

Biological predictors of chemotherapy-induced peripheral neuropathy (CIPN): MASCC neurological complications working group overview.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating condition associated with a number of chemotherapeutic agents. Drugs commonly implicated in the development of CIPN include platinum agents, taxanes, vinca alkaloids, bortezomib, and thalidomide analogues. As a drug response can vary between individuals, it is hypothesized that an individual's specific genetic variants could impact the regulation of genes involved in drug pharmacokinetics, ion channel functioning, neurotoxicity, and DNA repair, which in turn affect CIPN development and severity. Variations of other molecular markers may also affect the incidence and severity of CIPN. Hence, the objective of this review was to summarize the known biological (molecular and genomic) predictors of CIPN and discuss the means to facilitate progress in this field.