tbuckley/cabot-search huggingface dataset:
Synovial Sarcoma in Children, Adolescents, and Young Adults: A Report From the Children's Oncology Group ARST0332 Study
Authors: Rajkumar Venkatramani, Wei Xue, R. Lor Randall, Suzanne Wolden, James Anderson, Dolores Lopez-Terrada, Jennifer Black, Simon C. Kao, Barry Shulkin, Andrew Ostrenga, Alberto Pappo, Sheri L. Spunt
Journal: Journal of Clinical Oncology (2021)

Synovial sarcoma (SS) is the second most common malignant soft tissue tumor in children. ARST0332 evaluated a risk-based treatment strategy for young patients with soft tissue sarcoma designed to limit therapy for low-risk (LR) disease and to test neoadjuvant chemoradiotherapy for unresected higher-risk disease.Newly diagnosed patients with SS age < 30 years were assigned to four treatment arms based on disease features: A (surgery only), B (55.8 Gy radiotherapy [RT]), C (ifosfamide and doxorubicin [ID] chemotherapy plus 55.8 Gy RT), and D (neoadjuvant ID and 45 Gy RT, then surgery and RT boost based on margins followed by adjuvant ID). Patients treated in Arms A and B were considered LR, arms C and D without metastases as intermediate-risk (IR), and those with metastases as high-risk (HR).Of the 146 patients with SS enrolled, 138 were eligible and evaluable: LR (46), IR (71), and HR (21). Tumors were 80% extremity, 70% > 5 cm, 70% high-grade, 62% invasive, 95% deep, and 15% metastatic. Treatment was on arm A (29.7%), B (3.6%), C (16.7%), and D (50%). There were no toxic deaths and four unexpected grade 4 adverse events. By risk group, at a median follow-up of 6.8 years, estimated 5-year event-free survival was LR 82%, IR 70%, and HR 8%, and overall survival was LR 98%, IR 89%, and HR 13%. After accounting for the features that defined risk category, none of the other patient or disease characteristics (age, sex, tumor site, tumor invasiveness, and depth) improved the risk stratification model.The risk-based treatment strategy used in ARST0332 produced favorable outcomes in patients with nonmetastatic SS relative to historical controls despite using RT less frequently and at lower doses. The outcome for metastatic SS remains unsatisfactory and new therapies are urgently needed.
Abstract P209: Like Parent, Like Child? Examining Associations Among Parent And Emerging Adult Intuitive Eating
Authors: Blair Burnette, Vivienne Hazzard, Samantha Hahn, Dianne R Neumark-Sztainer
Journal: Circulation (2022)

Introduction: Intuitive eating (IE) is an approach that emphasizes relying on hunger and satiety cues to guide eating. Accumulating data highlight positive associations between IE and mental health and health-promoting behaviors, and some preliminary data suggest increasing IE might benefit cardiometabolic markers. However, little is known about what helps individuals eat intuitively. Although caregivers’ own eating patterns often shape those of their children, no known research to date has explored familial associations of IE. Elucidating factors that foster health-promoting behaviors is crucial to inform interventions that reduce cardiovascular disease. Objective: This cross-sectional, population-based study examined the concordance of IE between caregivers and their emerging adult children, and associations between concordance and sociodemographic characteristics and weight perceptions. Method: Data came from the second wave of the population-based, longitudinal EAT and F-EAT 2010-2018 studies. The analytic sample included 891 emerging adults (53.6% female; M age=22.0) and their primary caregiver who were diverse across race/ethnicity and socioeconomic status (SES). Caregivers and emerging adults were grouped into dyads: (1) neither are intuitive eaters ( n =194); (2) emerging adult only is an intuitive eater ( n =203); (3) caregiver only is an intuitive eater ( n =218); and, (4) both are intuitive eaters ( n =289). Chi-square analyses and independent samples t -tests examined differences across dyads. Results: Caregiver and emerging adult IE were weakly correlated ( r =.07, p =.03). Dyads differed across race/ethnicity, SES, and weight perceptions. Concordant dyads who ate intuitively were more likely to be high SES and perceive their weight as “about right,” whereas concordant dyads who did not eat intuitively were more likely to be low SES and perceive their weight as “overweight.” Asian emerging adults were more likely to belong to concordant non-intuitive eater dyads, whereas White and Black emerging adults were more likely to belong to concordant intuitive eater dyads. Discordant dyads were generally distinguished by weight perceptions. Emerging adults who shared their caregiver’s perception that their weight was “overweight” were less likely to be intuitive eaters (even if their caregivers were). Discussion: In this sample, weight perceptions were strongly related to IE, and IE differed across race and SES. Individuals who perceived their own weight as “overweight” were less likely to be intuitive eaters, as well as emerging adults whose caregivers perceived their weight as “overweight.” Rather than motivate healthy eating, perceiving one’s weight as “overweight” might actually hinder IE. Longitudinal research is needed to evaluate the temporality of associations, and future work is needed to explore the role of IE in cardiovascular disease risk.
MAPK Pathway Genetic Alterations Are Associated with Prolonged Overall Survival in Low-Grade Serous Ovarian Carcinoma
Authors: Beryl Manning-Geist, Sushmita Gordhandas, Ying L. Liu, Qin Zhou, Alexia Iasonos, Arnaud Da Cruz Paula, Diana Mandelker, Kara Long Roche, Oliver Zivanovic, Anna Maio, Yelena Kemel, Dennis S. Chi, Roisin E. O'Cearbhaill, Carol Aghajanian, Britta Weigelt, M. Herman Chui, Rachel N. Grisham
Journal: Clinical Cancer Research (2022)

To characterize the somatic mutational landscape, investigate associations between genetic alterations and clinical outcomes, and determine the prevalence of pathogenic germline mutations in low-grade serous ovarian carcinomas (LGSC).
Clinical Outcomes Related to Background Diuretic Use and New Diuretic Initiation in Patients With HFrEF
Authors: James P. Curtain, Ross T. Campbell, Mark C. Petrie, Alice M. Jackson, William T. Abraham, Akshay S. Desai, Kenneth Dickstein, Lars Køber, Jean L. Rouleau, Karl Swedberg, Michael R. Zile, Scott D. Solomon, Pardeep S. Jhund, John J.V. McMurray
Journal: JACC Heart Failure (2022)
Advisory Board and Contents
Authors: Jerry Madukwe, Jessica Miles, Fred Kop, Patrick Scheffmann, Michelle Arkin, Matthew Banks, Andrew Bate, Mary Bebawy, Jeffrey Benovic, Jacqueline Crawley, Debbie Hay, Stephanie Laszlo, Hunyady Magnus, Ingelman-Sundberg Michael, Kassiou Kum, Kum Khanna, Brian Kobilka, Jenny Lam, Michel Lazdunski, Fiona Marshall, Ruth Nussinov, Avner Schlessinger, Martina Schmidt, Harald Sitte, Rachel Tyndale, Ming-Wei Wang, Stephen Watson, Stephen Waxman, Matthew Webber, Ji-Young Park, Chang-Han Lee, Marco Herrera-Barrera, Gaurav Sahay
Journal: Trends in Pharmacological Sciences (2022)
REPEATED SOCIAL DEFEAT ENHANCES CACL2-INDUCED ABDOMINAL AORTIC ANEURYSM EXPANSION BY INHIBITING EARLY FIBROTIC RESPONSE VIA MAPK-MKP-1 PATHWAY
Authors: Hiroshi Kubota, Hiroyuki Yamada, Takeshi Sugimoto, Noriyuki Wakana, Satoaki Matoba
Journal: Journal of the American College of Cardiology (2022)
Consolidation and Maintenance in Newly Diagnosed Multiple Myeloma
Authors: Pieter Sonneveld, Meletios A. Dimopoulos, Meral Beksac, Bronno van der Holt, Sara Aquino, Heinz Ludwig, Sonja Zweegman, Thilo Zander, Elena Zamagni, Ruth Wester, Roman Hajek, Lucia Pantani, Luca Dozza, Francesca Gay, AnneMaria Cafro, Luca De Rosa, Annamaria Morelli, Henrik Gregersen, Nina Gulbrandsen, Petra Cornelisse, Rosella Troia, Stefania Oliva, Vincent van de Velden, KaLung Wu, Paula F. Ypma, Gerard Bos, Mark-David Levin, Luca Pour, Christoph Driessen, Annemiek Broijl, Alexandra Croockewit, Monique C. Minnema, Anders Waage, Cecilie Hveding, Niels W. C. J. van de Donk, Massimo Offidani, Giuseppe A. Palumbo, Andrew Spencer, Mario Boccadoro, Michele Cavo
Journal: Journal of Clinical Oncology (2021)

PURPOSE To address the role of consolidation treatment for newly diagnosed, transplant eligible patients with multiple myeloma in a controlled clinical trial. PATIENTS AND METHODS The EMN02/HOVON95 trial compared consolidation treatment with two cycles of bortezomib, lenalidomide, and dexamethasone (VRD) or no consolidation after induction and intensification therapy, followed by continuous lenalidomide maintenance. Primary study end point was progression-free survival (PFS). RESULTS Eight hundred seventy-eight eligible patients were randomly assigned to receive VRD consolidation (451 patients) or no consolidation (427 patients). At a median follow-up of 74.8 months, median PFS with adjustment for pretreatment was prolonged in patients randomly assigned to VRD consolidation (59.3 v 42.9 months, hazard ratio [HR] = 0.81; 95% CI, 0.68 to 0.96; P = .016). The PFS benefit was observed across most predefined subgroups, including revised International Staging System (ISS) stage, cytogenetics, and prior treatment. Revised ISS3 stage (HR, 2.00; 95% CI, 1.41 to 2.86) and ampl1q (HR, 1.67; 95% CI, 1.37 to 2.04) were significant adverse prognostic factors. The median duration of maintenance was 33 months (interquartile range 13-86 months). Response ≥ complete response (CR) after consolidation versus no consolidation before start of maintenance was 34% versus 18%, respectively ( P &lt; .001). Response ≥ CR on protocol including maintenance was 59% with consolidation and 46% without ( P &lt; .001). Minimal residual disease analysis by flow cytometry in a subgroup of 226 patients with CR or stringent complete response or very good partial response before start of maintenance demonstrated a 74% minimal residual disease–negativity rate in VRD-treated patients. Toxicity from VRD was acceptable and manageable. CONCLUSION Consolidation treatment with VRD followed by lenalidomide maintenance improves PFS and depth of response in newly diagnosed patients with multiple myeloma as compared to maintenance alone.
Abstract P148: Modifiable Obesogenic Behaviors Among Latino Adolescents With Suspected Non-alcoholic Fatty Liver Disease (NAFLD)
Authors: Luis A Rodriguez, Anjali Gopalan, Malini Chandra, Jeanne A Darbinian, Louise C Greenspan, Joan C Lo
Journal: Circulation (2022)

Non-alcoholic fatty liver disease (NAFLD) disproportionally affects US children of Latino descent, who also have a higher burden of obesity and type 2 diabetes. We previously found significant associations between diet and sedentary behaviors and weight status, but it is unclear if these measured behaviors are associated with suspected NAFLD among Latino adolescents with obesity, which was the objective of this study. We used cross-sectional data from 10,087 Latino adolescents ages 13-17 years in northern California with a well-child visit in 2016-2019, health behavior assessment, and BMI ≥95th percentile. Adolescents self-reported on 4 daily obesogenic behaviors at the visit: 1) consuming &lt;5 servings of fruits/vegetables; 2) drinking ≥1 juice/soda (12oz); 3) exercising/playing sports for &lt;60 minutes; and 4) &gt;2 hours of screen time. Suspected NAFLD was classified by serum alanine transaminase level ≥44 U/L (girls) and ≥52 U/L (boys). We used logistic regression to examine the associations of obesogenic behaviors with NAFLD, adjusting for age, gender, household language preference (English/Spanish), neighborhood deprivation index (quartiles), and Class 1, 2, and 3 obesity. Among 10,087 Latino adolescents with obesity, 88% (8,877) had ≥1 obesogenic behaviors and 10% (1012) had suspected NAFLD. None of the obesogenic behaviors were associated with NAFLD in unadjusted or adjusted models. Boys (vs girls) had higher odds of NAFLD (OR 2.2; 95% CI: 1.9-2.5), as did older adolescents (ages 16-17 vs 13-15, OR 1.7; 1.5-1.9) and those with more severe obesity (OR 2.2; 1.9-2.5, and OR 3.0; 2.5-3.6 for Class 2 and 3 (vs Class 1) obesity, respectively). In summary, older age, male gender and severe obesity were risk factors for suspected NAFLD while binary assessment of diet and sedentary behaviors were not, suggesting that more precise diet and exercise assessment tools are needed. The high burden of obesogenic behaviors and strong association of severe obesity with NAFLD point to important actionable targets for pediatric primary care.
In acute PE, triage for home treatment using the Hestia rule vs. sPESI was noninferior for 30-d clinical outcomes
Authors: Bethany Samuelson Bannow
Journal: Annals of Internal Medicine (2022)

Source Citation Roy PM, Penaloza A, Hugli O, et al. Triaging acute pulmonary embolism for home treatment by Hestia or simplified PESI criteria: the HOME-PE randomized trial. Eur Heart J. 2021;42:3146-57. 34363386
Evaluating the Impact of the Clean Heat Program on Air Pollution Levels in New York City
Authors: Lyuou Zhang, Mike Z. He, Elizabeth A. Gibson, Frederica Perera, Gina S. Lovasi, Jane E. Clougherty, Daniel Carrión, Kimberly Burke, Dustin Fry, Marianthi-Anna Kioumourtzoglou
Journal: Environmental Health Perspectives (2021)
After DES implantation, DAPT for 1 y vs. ≤6 mo increased major bleeding in patients with high baseline bleeding risk
Authors: James M. Brophy
Journal: Annals of Internal Medicine (2022)

Source Citation Palmerini T, Bruno AG, Redfors B, et al. Risk–benefit of 1-year DAPT after DES implantation in patients stratified by bleeding and ischemic risk. J Am Coll Cardiol. 2021;78:1968-86. 34763774
Maturation of GFR in Term-Born Neonates: An Individual Participant Data Meta-Analysis
Authors: Nori J.L. Smeets, Joanna IntHout, Maurice J.P. van der Burgh, George J. Schwartz, Michiel F. Schreuder, Saskia N. de Wildt
Journal: Journal of the American Society of Nephrology (2022)

Significance Statement The evidence from individual studies to support the maturational pattern of GFR in healthy, term-born neonates is inconclusive. This paper describes GFR reference values in the first month of life using an individual participant data meta-analysis of reported measured GFR (mGFR) data using data from 881 neonates. GFR doubled in the first 5 days after birth, from 19.6 to 40.6 ml/min per 1.73 m 2 , and then more gradually increased to 59.4 ml/min per 1.73 m 2 by 4 weeks of age. GFR was best estimated by 0.31×height (cm)/serum creatinine (mg/dl). These mGFR reference values and more accurate GFR estimations can help to identify altered GFR in term-born neonates; however, further validation of the eGFR equation is needed. Background The evidence from individual studies to support the maturational pattern of GFR in healthy, term-born neonates is inconclusive. We performed an individual participant data (IPD) meta-analysis of reported measured GFR (mGFR) data, aiming to establish neonatal GFR reference values. Furthermore, we aimed to optimize neonatal creatinine-based GFR estimations. Methods We identified studies reporting mGFR measured by exogenous markers or creatinine clearance (CrCL) in healthy, term-born neonates. The relationship between postnatal age and clearance was investigated using cubic splines with generalized additive linear mixed models. From our reference values, we estimated an updated coefficient for the Schwartz equation (eGFR [ml/min per 1.73 m 2 ]=(k×height [cm])/serum creatinine [mg/dl]). Results Forty-eight out of 1521 screened articles reported mGFR in healthy, term-born neonates, and 978 mGFR values from 881 neonates were analyzed. IPD were available for 367 neonates, and the other 514 neonates were represented by 41 aggregated data points as means/medians per group. GFR doubled in the first 5 days after birth, from 19.6 (95% CI, 14.7 to 24.6) to 40.6 (95% CI, 36.7 to 44.5) ml/min per 1.73 m 2 , and then increased more gradually to 59.4 (95% CI, 45.9 to 72.9) ml/min per 1.73 m 2 by 4 weeks of age. A coefficient of 0.31 to estimate GFR best fitted the data. Conclusions These reference values for healthy, term-born neonates show a biphasic increase in GFR, with the largest increase between days 1 and 5. Together with the re-examined Schwartz equation, this can help identify altered GFR in term-born neonates. To enable widespread implementation of our proposed eGFR equation, validation in a large cohort of neonates is required.
Gene expression signatures identify biologically and clinically distinct tuberculosis endotypes
Authors: Andrew R. DiNardo, Tanmay Gandhi, Jan Heyckendorf, Sandra L. Grimm, Kimal Rajapakshe, Tomoki Nishiguchi, Maja Reimann, H. Lester Kirchner, Jaqueline Kahari, Qiniso Dlamini, Christoph Lange, Torsten Goldmann, Sebastian Marwitz, None Abhimanyu, Jeffrey D. Cirillo, Stefan H.E. Kaufmann, Mihai G. Netea, Reinout van Crevel, Anna M. Mandalakas, Cristian Coarfa
Journal: European Respiratory Journal (2022)

Background In vitro , animal model and clinical evidence suggests that tuberculosis is not a monomorphic disease, and that host response to tuberculosis is protean with multiple distinct molecular pathways and pathologies (endotypes). We applied unbiased clustering to identify separate tuberculosis endotypes with classifiable gene expression patterns and clinical outcomes. Methods A cohort comprised of microarray gene expression data from microbiologically confirmed tuberculosis patients was used to identify putative endotypes. One microarray cohort with longitudinal clinical outcomes was reserved for validation, as were two RNA-sequencing (seq) cohorts. Finally, a separate cohort of tuberculosis patients with functional immune responses was evaluated to clarify stimulated from unstimulated immune responses. Results A discovery cohort, including 435 tuberculosis patients and 533 asymptomatic controls, identified two tuberculosis endotypes. Endotype A is characterised by increased expression of genes related to inflammation and immunity and decreased metabolism and proliferation; in contrast, endotype B has increased activity of metabolism and proliferation pathways. An independent RNA-seq validation cohort, including 118 tuberculosis patients and 179 controls, validated the discovery results. Gene expression signatures for treatment failure were elevated in endotype A in the discovery cohort, and a separate validation cohort confirmed that endotype A patients had slower time to culture conversion, and a reduced cure rate. These observations suggest that endotypes reflect functional immunity, supported by the observation that tuberculosis patients with a hyperinflammatory endotype have less responsive cytokine production upon stimulation. Conclusion These findings provide evidence that metabolic and immune profiling could inform optimisation of endotype-specific host-directed therapies for tuberculosis.
Abstract EP64: Creating A Comprehensive Lifestyle Intervention For Stroke Survivors
Authors: Ryan Bailey, Natalie Miner, Sarah Waddoups, Julie Metos, Nancy A Allen
Journal: Circulation (2022)

Purpose: Approximately 795,000 people experience a stroke each year, 23% of which are recurrent events. Among stroke survivors, comprehensive lifestyle intervention (CLI) is recommended for secondary stroke prevention, and obesity and glucose management. American Heart Association (AHA) guidelines for CLI recommend that interventions address physical activity and dietary intake through ≥14 sessions delivered over ≥6 months. Few existing programs meet these recommendations. Therefore, the purpose of this project was to create a 6-month, 14-session CLI using stakeholder input that adheres to the AHA recommendations. Methods: The study team, which included individuals with expertise in stroke, nutrition, nursing, and occupational therapy, adapted the content, structure, and format of an existing 1-year, 22-session diabetes prevention program, the Group Lifestyle Balance—CVA (GLB-CVA), to create the CLI. An advisory board of health professionals with expertise in nutrition, exercise science, occupational therapy, and physical therapy then provided feedback on the CLI through 2 focus group meetings. Qualitative data from focus groups were transcribed and used to modify the CLI. Results: Study team adaptions included shortening the GLB-CVA to 14 sessions, tailoring content to accommodate stroke-related disability (e.g., sitting-based and one-handed exercise and cooking recommendations), and including a care-partner. Advisory board modifications included shortening individual sessions, simplifying language, and ensuring physical activity and dietary recommendations were appropriate for stroke survivors. Additional modifications are listed in the table. Conclusions: Evidence-based CLIs for stroke survivors are lacking. Our adapted CLI meets the AHA recommendations for CLI and provides recommendations appropriate for stroke survivors based on expert opinion. Future directions include efficacy testing of the adapted CLI and intervention implementation in clinical and community settings.
The HNF4α-BC200-FMR1–Positive Feedback Loop Promotes Growth and Metastasis in Invasive Mucinous Lung Adenocarcinoma
Authors: Xiong Chen, Yujie Zhao, Daxuan Wang, Ying Lin, Jihuan Hou, Xiaolin Xu, Jianben Wu, Linhai Zhong, Yitong Zhou, Jinying Shen, Wenqing Zhang, Hanwei Cao, Xiaoting Hong, Tianhui Hu, Yan-yan Zhan
Journal: Cancer Research (2021)

Invasive mucinous lung adenocarcinoma (IMA) is a subtype of lung adenocarcinoma with a strong invasive ability. IMA frequently carries "undruggable" KRAS mutations, highlighting the need for new molecular targets and therapies. Nuclear receptor HNF4α is abnormally enriched in IMA, but the potential of HNF4α to be a therapeutic target for IMA remains unknown. Here, we report that P2 promoter-driven HNF4α expression promotes IMA growth and metastasis. Mechanistically, HNF4α transactivated lncRNA BC200, which acted as a scaffold for mRNA binding protein FMR1. BC200 promoted the ability of FMR1 to bind and regulate stability of cancer-related mRNAs and HNF4α mRNA, forming a positive feedback circuit. Mycophenolic acid, the active metabolite of FDA-approved drug mycophenolate mofetil, was identified as an HNF4α antagonist exhibiting anti-IMA activities in vitro and in vivo. This study reveals the role of a HNF4α-BC200-FMR1-positive feedback loop in promoting mRNA stability during IMA progression and metastasis, providing a targeted therapeutic strategy for IMA. SIGNIFICANCE: Growth and metastatic progression of invasive mucinous lung adenocarcinoma can be restricted by targeting HNF4α, a critical regulator of a BC200-FMR1-mRNA stability axis.