tbuckley/cabot-search huggingface dataset:
Abstract P056: Adolescent Self-Reported School Environment and Obesity Prevalence, the Fragile Families and Child Wellbeing Study
Authors: Zerleen S Quader, Shakira F Suglia
Journal: Circulation (2019)

Introduction: Childhood obesity continues be a major public health concern in the United States, and disproportionately affects racial/ethnic minorities and children of lower socioeconomic status. Social environments such as schools are particularly influential in shaping child and adolescent health, and represent an important target for interventions to improve health behaviors. Positive school environments, those that are safe, supportive, respectful, and engaging, have been shown to be associated with adolescent health behaviors; however, few studies have examined whether a positive school climate can influence physical health, such as obesity status. Hypothesis: We hypothesized that adolescents’ self-reported positive school environment would be associated with a lower prevalence of obesity in a disadvantaged population and that this association may differ by sex. Methods: Data were from the sixth wave of the Fragile Families and Child Wellbeing Study, a cohort of children born between 1998 and 2000, approximately two-thirds of whom were born to unmarried parents. Adolescents were, on average, 15 years of age at the time of the assessment and had height and weight measured during a home visit. Positive school environment was operationalized using adolescent self-reported responses to survey questions examining school connectedness, school climate (teacher quality and student behavior towards teachers), and presence of bullying behaviors in the past month. A cumulative school environment score was created, ranging from zero to five, with a score of four or five defined as a positive school environment (i.e. high levels of connectedness, positive climate, and no bullying). The final analytic sample size was 1,044 adolescents. Log binomial regression was used to estimate prevalence ratios for obesity. Results: Twenty-six percent of the sample was obese, and 45% reported a positive school environment. Crude and adjusted models were similar. After adjustment for race/ethnicity, parent marital status at first wave, and student receipt of free lunch, there did not appear to be an association between positive school environment and prevalence of obesity among boys (PR: 1.1; (0.8, 1.4)). Among girls, there was a slight inverse association between positive school environment and prevalence of obesity (PR: 0.8; (0.6, 1.1)), however this was not statistically significant. Conclusions: Results suggest that a more positive school environment could be associated with a lower prevalence of obesity among adolescent girls in a high-risk population. However, because of the cross-sectional nature of this analysis, results should be interpreted with caution, as temporality cannot be established. Future work should explore the use of validated measures of school environment to improve measurement and explore whether interactions exist between school environment and adolescents’ sex.
Altered neuronal migratory trajectories in human cerebral organoids derived from individuals with neuronal heterotopia
Authors: Johannes Klaus, Sabina Kanton, Christina Kyrousi, Ane Cristina Ayo-Martin, Rossella Di Giaimo, Stephan Riesenberg, Adam C. O’Neill, J. Gray Camp, Chiara Tocco, Malgorzata Santel, Ejona Rusha, Micha Drukker, Mariana Schroeder, Magdalena Götz, Stephen P. Robertson, Barbara Treutlein, Silvia Cappello
Journal: Nature Medicine (2019)
Evaluation of targeted bone marrow arrest by G1T28, a CDK4/6 inhibitor in clinical development to reduce chemotherapy-induced myelosuppression.
Authors: Patrick J. Roberts, Hannah S. White, Jessica A. Sorrentino, Henko Tadema, Mark Sale, Renger G. Tiessen, John E. Bisi, Karenann M. Makhuli, Ewoud-Jan van Hoogdalem, Rajesh K. Malik, Jay C. Strum
Journal: Journal of Clinical Oncology (2015)

2529 Background: Myelosuppression is the major dose-limiting toxicity of chemotherapy, which limits dose intensity. G1T28 is a highly potent and selective CDK4/6 inhibitor in development as an IV agent to provide targeted bone marrow chemoprotection in patients with CDK4/6-independent tumors. Hematopoietic stem and progenitor cells (HSPCs) are dependent upon CDK4/6 for proliferation; G1T28 induces a transient G1 cell cycle arrest that renders HSPCs resistant to the cytotoxic effects of chemotherapy. In preclinical models, this results in faster recovery of all blood cell counts following chemotherapy and preservation of long-term hematopoietic function. Methods: To rationally design tolerable and active chemotherapy combination regimens with reduced multi-lineage myelosuppression, the magnitude and duration of G1T28-induced HSPC G1 arrest in human bone marrow was characterized. Data from 3 species (mouse, rat, dog) were used to evaluate dose response relationships for HSPC G1 cell cycle arrest and to construct a cross-species allometrically-scaled PK/PD model. Model simulations and human PK/PD data from a Phase I trial (NCT02243150) were used to predict the biologically effective dose (BED) in humans. In this trial, the BED was assessed by obtaining bone marrow aspirates and evaluating G1 arrest of HSPCs by flow cytometry. Results: Preclinical PK/PD modeling outputs and clinical data predicted the BED in humans to be 192 mg/m2. Specifically, a 15mg/kg dose of G1T28 in dogs produced robust and sustained bone marrow arrest for ~24 hours and had a similar PK exposure to the predicted human BED. A single bone marrow aspirate from 12 subjects following 192 mg/m2 (baseline, n = 5; 24 h post-G1T28, n = 3, or 32 h post-G1T28, n = 4) demonstrated a robust G1 arrest of multiple progenitor subsets at 24 h, with early progenitors persisting in G1 arrest to 32 h. Conclusions: A single IV administration of G1T28 at the BED of 192 mg/m2 produced robust inhibition of HSPCs within the bone marrow for > 24 hours. Based on these results, Phase 1b/2a studies are planned to evaluate the potential of G1T28 in reducing multi-lineage chemotherapy-induced myelosuppression. Clinical trial information: NCT02243150.
Pembrolizumab (pembro) plus axitinib (axi) versus sunitinib as first-line therapy for locally advanced or metastatic renal cell carcinoma (mRCC): phase III KEYNOTE-426 study.
Authors: Thomas Powles, Elizabeth R. Plimack, Viktor Stus, Rustem Airatovich Gafanov, Robert E. Hawkins, Dmitry Nosov, Frederic Pouliot, Boris Yakovlevich Alekseev, Denis Soulieres, Bohuslav Melichar, Ihor Vynnychenko, Anna Kryzhanivska, Igor Bondarenko, Sergio Jobim Azevedo, Delphine Borchiellini, Qiong Shou, Rodolfo F. Perini, Mei Chen, Michael B. Atkins, Brian I. Rini
Journal: Journal of Clinical Oncology (2019)

543 Background: A phase 1b study of pembro (anti–PD-1) plus axi (VEGFR-TKI) showed promising antitumor activity and manageable safety in patients (pts) with previously untreated mRCC. The global, open-label, phase 3 KEYNOTE-426 study assessed the efficacy and safety of pembro + axi vs sunitinib as first-line therapy for mRCC (NCT02853331). Methods: Eligible pts with clear-cell mRCC, no previous systemic therapy for mRCC, and KPS ≥70% were randomized 1:1 to pembro 200 mg IV Q3W for a maximum of 35 cycles plus axi 5 mg orally BID or sunitinib 50 mg orally QD (4-wk on/2-wk off schedule). Treatment was given until PD, intolerable toxicity, or pt/investigator decision. Randomization was stratified by IMDC risk group and geographic region. Primary endpoints were OS and PFS (RECIST v1.1 by blinded, independent central review [BICR]). ORR was the key secondary endpoint. At the protocol-specified first interim analysis, the superiority thresholds were P = 0.0001 for OS, 0.0013 for PFS, and 0.025 for ORR (if OS and PFS were significant). Results: 861 pts were randomized: 432 to pembro + axi, 429 to sunitinib. After a 12.8-mo median follow-up, 59.0% of pts in the pembro + axi arm and 43.1% in the sunitinib arm remained on treatment. Pembro + axi significantly improved OS (HR 0.53 [95% CI 0.38-0.74]; P &lt; 0.0001; 12-mo rate 89.9% vs 78.3%), PFS (HR 0.69 [95% CI 0.57-0.84]; P = 0.0001; median 15.1 vs 11.1 mo), and ORR (59.3% vs 35.7%; P &lt; 0.0001). Duration of response was prolonged with pembro + axi (median not reached vs 15.2 mo). The pembro + axi benefit was observed in all subgroups tested, including all IMDC risk and PD-L1 expression subgroups. Treatment-related AEs were grade 3-5 in 62.9% of pts in the pembro + axi arm vs 58.1% in the sunitinib arm and led to regimen discontinuation in 6.3% vs 10.1%. Conclusions: Pembrolizumab + axitinib provided superior OS, PFS, and ORR compared with sunitinib and had manageable safety in pts with previously untreated, advanced or metastatic clear-cell RCC. These data suggest that pembrolizumab + axitinib should be a new standard of care for this population. Clinical trial information: NCT02853331.
Abstract 17180: Impact of Sinus Rhythm Maintenance on Exercise Tolerance After Catheter Ablation in Patients With Paroxysmal Atrial Fibrillation
Authors: Kyoshiro Fukasawa, Koji Fukuda, Makoto Nakano, Yuhi Hasebe, Yoshitaka Kimura, Takahiko Chiba, Keita Miki, Hiroaki Shimokawa
Journal: Circulation (2016)

Background: Although catheter ablation is widely used to maintain sinus rhythm and improve symptoms in patients with paroxysmal atrial fibrillation (PAF), it remains to be elucidated whether the ab...
Ovarian preservation in young patients with early stage endometrial carcinoma.
Authors: Lin Lv, Zhilan Peng
Journal: Journal of Clinical Oncology (2015)

e16511 Background: Ovarian preservation in young patients with endometrial carcinoma is still controversial. The purpose of this study was to clarify the frequency and risk factors of ovarian metastasis and to assess the feasibility of ovarian preservation in young patients with early stage endometrial carcinoma. Methods: A retrospective review was performed on all patients with endometrial cancer diagnosed at age 45 or younger from December 1995 until December 2009 who were surgically treated at West China Second University Hospital. Clinicopathological data and follow-up results were extracted. Results: Ovarian metastasis was detected in 14 (6.6%) of 213 patients who underwent primary surgical treatment. The independent risk factors of ovarian metastasis were lymph node metastasis, non-endometrioid histology and deep myometrial invasion. Ovary-preserving surgery was performed in 36 patients (age range 22-42 years) who had strong desire of ovarian preservation after being given a full explanation of potential risks and met all the following criteria including (1) with either grade-1 or grade-2 endometrioid adenocarcinoma, (2) with confirmation of the absence of evidence suggesting advanced disease and risk factors of ovarian metastasis intraoperatively, (3) with confirmation of the absence of ovarian metastasis and synchronous primaries by ovarian biopsy, and (4) without family history of cancer. A thorough surgical staging including hysterectomy, pelvic and para-aortic lymphadenectomy, peritoneal washings and biopsy of the ovaries was conducted to confirm the absence of known risk factors in all the patients with ovarian preservation. Median follow-up duration was 87 months (rang 56-225 months). Of the 36 patients, 34 (94.4%) had been clinically free of cancer since operation. One recurrence and one metachronous primary ovarian malignancy occurred during follow-up. There’s no cancer-related death. Conclusions: Ovary-preserving surgery could be the treatment of choice for young patients with early stage endometrial carcinoma if a thorough surgical staging is conducted with the confirmation of the absence of predictable risk factors. Close follow-up is essential.
Characterization of tumor mutational burden (TMB), PD-L1, and DNA repair genes to assess correlation with immune checkpoint inhibitors (ICIs) response in metastatic renal cell carcinoma (mRCC).
Authors: Matthew Labriola, Jason Zhu, Rajan Gupta, Shannon McCall, Jennifer Jackson, James R White, Elizabeth Weingartner, Eric Kong, Peter Simone, Eniko Papp, Kelly Gerding, John Simmons, Daniel J. George, Tian Zhang
Journal: Journal of Clinical Oncology (2019)

e16079 Background: ICIs have revolutionized treatment for mRCC; however there are limited predictive biomarkers for response to ICIs. PD-L1 status is still controversial, demonstrating little predictive utility in mRCC. TMB is predictive for response to ICIs in melanoma and non-small cell lung cancer (NSCLC), but has not been validated in mRCC. Here, we assess the correlations between TMB and PD-L1 status with outcomes to ICI treatment in mRCC. Methods: 34 patients (pts) with mRCC who had previously received ICIs at Duke Cancer Institute were identified. Tumor samples were retrospectively evaluated using a Personal Genome Diagnostics Assay for somatic variants across &gt; 500 genes, as well as TMB and microsatellite status. PD-L1 status was tested via the Dako 28-8 PD-L1 IHC assay. Deidentified clinical information was extracted from the medical record and tumor response was evaluated based on RECIST criteria. Results: Pts were grouped by overall response following ICI therapy into either progressive disease (“PD”, n = 18) or disease control group (“DC”, n = 16), defined as either stable disease, partial response, or complete response. Pts displayed a TMB range from 0.36 to 12.24 mutations/Mb with a mean score of 2.83 muts/Mb, with no significant difference between the PD and DC groups (mean 3.01 muts/Mb vs. 2.63 muts/Mb, p &gt; 0.05). 9 of 32 evaluable samples were PD-L1 positive, with 4 in the PD group and 5 in the DC group. Notably, the DC group displayed a significant enrichment of mutations in genes affiliated with DNA repair (including BRCA1, BRCA2, FANCA, FANCB, FANCG, FANCM, MSH3, MSH6, RAD50, RAD51C, RAD51D, RAD54B, RECQL4, and SLX4; p = 0.0444). DNA damage gene mutations were found in 8/10 (80%) metastatic tumor specimens and 14/24 (58%) primary tumors. Conclusions: Overall, in this mRCC cohort, neither TMB nor PD-L1 correlated with patient outcomes or with ICI response. Furthermore, high TMB was not significantly associated with PD-L1 expression within the samples. The higher frequency of mutations in DNA repair genes in the DC group suggests potential use as a predictive signature for ICI response, warranting future prospective studies. Further studies with matched primary-metastatic samples would be beneficial to determine if DNA repair mutations occur more frequently in metastatic versus primary tumor specimens.
Change in knowledge and attitude about HIV/AIDS in sub-Saharan Africa, 1990–2017: an analysis of national survey data
Authors: Xiaochen Dai, Haidong Wang
Journal: The Lancet Global Health (2019)

BackgroundPeople's knowledge of and attitude to HIV/AIDS are key contributors to the success of public-health interventions. However, evidence on country-level HIV/AIDS knowledge and attitudes is still scarce across sub-Saharan countries. To address this knowledge gap, we have gathered evidence to estimate national trends in HIV/AIDS knowledge and attitude from 1990 to 2017 across 46 sub-Saharan African countries.MethodsWe retrieved national surveys that have indicators of HIV/AIDS knowledge and attitude from Global Health Data Exchange (GHDx). There are ten indicators of knowledge of HIV transmission and risk reduction and four indicators that reflect attitude towards people living with HIV/AIDS. We extracted individual-level data on knowledge and attitude in a systematic and consistent way and collapsed these into country-level estimates. Multi-level multiple imputation was used to impute missing indicators on country level and we used spatial-temporal Gaussian process regression (ST-GPR) to estimate the trend of each indicator in each country.FindingsWe included 313 national surveys in the study. From 1990 to 2017, most knowledge indicators slightly increased across all countries. However, the trends of knowledge on HIV mother-to-child transmission during pregnancy vary between countries, with significant decreasing trends in 18 of 46 countries including Kenya, Rwanda, and Zambia. For the attitude factors, we noted that the factors "willing to frequent a HIV-positive vendor", "willing to take care of a HIV-positive family members in the house", and "belief that a HIV-positive teacher should continue to work" all increased across countries. However, across the study period, people have become more reluctant to reveal a family member's positive status. In addition, our results indicate that men are slightly more knowledgeable about HIV/AIDS than are women.InterpretationIn sub-Saharan African countries, knowledge of HIV/AIDS increased slightly between 1990 and 2017, with people becoming more accepting of people with HIV/AIDS. Of concern is that knowledge about prevention of mother-to-child HIV transmission during pregnancy has not been improving as much, and is even decreasing in some countries. Of similar concern is that people are now less likely to reveal a family member's positive HIV status, suggesting that discrimination against people living with HIV/AIDS is still persistent and may be becoming worse. Efforts and resources are still needed to turn the tide in these areas.FundingUS National Institutes of Health and Bill & Melinda Gates Foundation.
Disclosure of industry payments to oncologists: Early open payments data.
Authors: Deborah Catherine Marshall, Madeleine E. Jackson, Jona Ashok Hattangadi
Journal: Journal of Clinical Oncology (2015)

6615 Background: The Open Payments program discloses industry payments to identified physicians (‘physician payments’). We characterize these payments by oncology specialty. Methods: We analyzed the December 2014 release of Open Payments data on physician payments made from August-December 2013. We characterized physician payments by type (general or research). We also evaluate physician ownership interests in reporting manufacturers. Data were aggregated by physician and oncology specialty [medical oncology (hematology/oncology, medical oncology, pediatric hematology/oncology); radiation oncology; and surgical oncology (surgical oncology, gynecologic oncology)]. We compared the number of physicians receiving payments to the total number of active physicians in each specialty in 2012 (AMA. Physician Characteristics and Distribution in the US. Chicago: AMA; 2014). Results: There were 82,213 payments to 9,893 oncology physicians (50% vs. 46% for all medical specialties) totaling $31 million (‘M’), Table. Payments for food/beverage were most common (79%) but represent only 10% of the total value. The most common nature of payment by total value was compensation for services (excluding consulting and CME) in medical oncology (38%), consulting fees in radiation oncology (30%), and education in surgical oncology (27%). Ownership interests totaled $8M in amount invested and $12M in total value of interest. Medical oncology had the highest proportion of physicians with ownership interest (1.7%) of oncology specialties. Conclusions: These data can inform policy-making and advocacy efforts for oncology specialties. Partially supported by the NIH (Grant TL1TR00098). Industry payments to oncology physicians, August-December 2013. Specialty Number of payments % of physicians receiving payments Total value: all payments Total value: general payments % Total value: research payments % Medical oncology 74,107 54% $26,317,128 $14,900,718 57% $11,416,410 43% Radiation oncology 4,612 31% $3,440,178 $1,048,742 30% $2,391,436 70% Surgical oncology 3,494 86% $1,108,222 $1,082,796 98% $25,426 2% All oncology 82,213 50% $30,865,528 $17,032,256 55% $13,833,272 45%
Abstract P273: The Association of Obstructive Sleep Apnea on Cardiac Parasympathetic Responses During Stress Testing: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Cecilia Castro-Diehl, Susan Redline, Richard Sloan, Glaucylara Reis Geovanini, Xu Wang, Younghoon Kwon, Steven Shea
Journal: Circulation (2019)

Introduction: Obstructive sleep apnea (OSA) may lead to abnormalities in the balance between sympathetic and parasympathetic activity at night; variation in daytime activity and responses to stress are less understood. Hypothesis: OSA is associated with reduced parasympathetic response from stress challenges. Method: In the Multi-Ethnic Study of Atherosclerosis (MESA) cohort (mean age 68yrs), 413 participants underwent in-home polysomnography. OSA severity was characterized by apnea-hypopnea index (AHI) as mild (5≤AHI&lt;15), moderate (15≤AHI&lt;30), severe (AHI≥30), or no OSA (AHI &lt;5 events/h) (referent). We examined High Frequency (HF)-heart rate variability (HRV), an index of cardiac parasympathetic modulation, during a standardized daytime stress challenge protocol: a baseline period followed by two mental stress tasks, the modified Stroop color-word conflict and an arithmetic task, each followed by a recovery period. We used linear mixed effects model with HF-HRV as outcome. Results: Participants with mild OSA (but not those with moderate or severe OSA) had lower levels of HF-HRV than those with no OSA (–0.36 log msec 2 , 95% CI –0.70, –0.02, P &lt;0.05) at baseline. Those with severe OSA had a smaller increase in HF-HRV during recovery than the no OSA group (–0.34% change, 95% CI –0.63, –0.06, P &lt;0.05) ( Table 1A ). Because OSA related cardiovascular disease may vary by age, a sensitivity analysis separately examining participants ≥65 and &lt; 65 yo suggested that those ≥65 years with mild and moderate OSA had greater HF-HRV reactivity to the tasks than those with no OSA, and those &lt;65 years with mild, moderate and severe OSA had a smaller increase in HF-HRV during recovery than those without OSA ( p -interaction=NS) (Table 1B). Conclusions: Our results showed reduced HRV at baseline and a decrease of the parasympathetic cardiac modulation with stress challenge associated with OSA severity. Findings were different according to age groups. Assessment of HRV may help identify individuals with OSA-related physiological abnormality.
Effect of increased dose of total body irradiation on graft failure associated with HLA-haploidentical transplantation in patients with severe haemoglobinopathies: a prospective clinical trial
Authors: Javier Bolaños-Meade, Kenneth R Cooke, Christopher J Gamper, Syed Abbas Ali, Richard F Ambinder, Ivan M Borrello, Ephraim J Fuchs, Douglas E Gladstone, Christian B Gocke, Carol Ann Huff, Leo Luznik, Lode J Swinnen, Heather J Symons, Stephanie A Terezakis, Nina Wagner-Johnston, Richard J Jones, Robert A Brodsky
Journal: The Lancet Haematology (2019)