tbuckley/cabot-search huggingface dataset:
Abstract 460: Sex-Related Changes in Physiological Cardiac Hypertrophy in Beta Arrestin-2 KO mice
Authors: Andrielle E Capote, David M Ryba, Shamim Chowdhury, Paola C Rosas, Ross J Solaro, Fernando A Dias, Beata M Wolska
Journal: Circulation Research (2019)

β-arrestin-2 (ARRB2) has an integral role in G-protein-coupled receptor regulation and signaling. Our lab has reported that biased ligands acting at the AT1-R promote ARRB2 signaling that increases contractility and reduces maladaptations in dilated cardiomyopathy. Our hypothesis is that ARRB2 is necessary for the physiological eccentric cardiac hypertrophic response associated with voluntary exercise. Methods and Results: Our study compared ARRB2 knockout (KO) and age matched FVBN control mice (NTG). Twelve-week-old age mice were divided into 4 groups. For a 6-week period ARRB2-KO and NTG were either sedentary or subjected to voluntary running. Records from wheels were obtained continuously through Wi-Fi and the data were analyzed weekly. Before exercise, baseline echocardiographic analyses were performed showing no apparent differences in cardiac function among the groups. Initially no differences were found in running parameters between ARRB2-KO and controls. However, beginning in the third week through the end of the exercise duration we found a decrease in the distance covered in ARRB2KO females compared with NTG females. After 6-weeks of exercise there was an increase in LA diameter, LV mass, LVIDd and HW/TL ratio only in NTG female compared with sedentary group suggesting ARRB2 sex-related differences in response to voluntary exercise. Although ARRB2 KO in C57/BL mice has been shown to alter myofilament Ca-sensitivity, we found no changes in myofilament Ca-sensitivity and post-translational modifications among all four groups. Conclusion: Our data suggest that ARRB2 is required for physiological hypertrophy caused by voluntary exercise only in female but not in male mice. Further studies are required to test whether ARRB2 is required for development of more stressful physiological hypertrophy during involuntary training regimens such as swimming or treadmill.
Abstract 120: Methamphetamine-induced Cardiomyopathy Associated With Mitochondrial Dysfunction, Cardiac Fibrosis and Hypertrophy
Authors: Chowdhury S Abdullah, Richa Aishwarya, Shafiul Alam, Mahboob Morshed, Gopi K Kolluru, James Traylor, Sumitra Miriyala, Manikandan Panchatcharam, Matthew D Woolard, Nicholas E Goeders, Xioa-Hong Lu, Paari S Dominic, Christopher G Kevil, A. Wayne Orr, Norman R Harris, Felicity N. E Gavins, Md. Shenuarin Bhuiyan
Journal: Circulation Research (2019)

Introduction: Methamphetamine (METH) is one of the most commonly abused illicit drugs in the United States, exerting a range of adverse effects upon multiple organ systems. Cardiovascular complications are among the major causes of death in METH users. METH-induced cardiomyopathy is a poorly characterized disease entity as METH-induced molecular perturbations, and histopathological changes in the heart remain under-explored. Objectives: We studied histopathology in the hearts of human METH users. We also observed the histological alteration and changes in mitochondrial function in mice that received ‘binge’ administration of METH. Methods and Results: We obtained 32 autopsy heart samples from humans with positive toxicology for chronic METH use and performed Sirius Red and Masson’s Trichrome (MT) staining on left ventricular (LV) sections. Notably, chronic METH user hearts showed intense perivascular and interstitial fibrosis in LVs. ‘Binge’ METH administration in mice for 4 weeks showed an increase in heart weight-to-tibia length and increase in myocyte cross-sectional area in WGA stained LVs compared to saline-treated mice. Sirius red and MT staining also showed an increase in perivascular and interstitial fibrosis in METH mice heart. Isolated mitochondria from METH-treated mice heart showed suppressed mitochondrial bioenergetics measured by Seahorse Analyzer. Immunoblotting in heart lysates and mitochondrial fractions showed altered mitochondrial dynamics regulatory proteins expression in METH mice compared to control saline group. METH-treated cultured neonatal rat ventricular cardiomyocytes also showed suppression of mitochondrial respiration and mitochondrial network disorganization indicating a direct effect of METH on cardiomyocytes. Conclusions: We report that maladaptive cardiac fibrotic remodeling is typical in a human and pre-clinical mouse model of METH abuse. ‘Binge’ METH exposure in mice induces cardiac hypertrophy, cardiac fibrosis, and suppression of mitochondrial respiration. Thus, chronic METH use induces maladaptive cardiac remodeling associated with mitochondrial dysfunction.
Factors affecting treatment in small cell and non-small cell lung cancer patients.
Authors: Phuong Ngo, Christina M Pinkston, Goetz H. Kloecker
Journal: Journal of Clinical Oncology (2019)

146 Background: Kentucky has the highest incidence of lung cancer death and despite improvements in treatment and survival, some small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) patients remain untreated. We looked at factors preventing these patients from receiving necessary treatment. Methods: Data was collected from the Kentucky Cancer Registry (KCR) for SCLC and NSCLC patients from 2012-2015 and included race, gender, age at diagnosis, treatment history, insurance and overall survival. Treatment included any combination of surgery, radiation, chemotherapy or immunotherapy. Patient demographics were summarized based on treatment status and derived odds ratio (OR) and 95% confidence intervals (CI) were reported. Significant associations were assessed at the p &lt; 0.05 level. Results: KCR identified 2,992 SCLC and 13,975 NSCLC patients from 2012-2015. More NSCLC patients [3,608 (25.8%)] were untreated than SCLC patients [621 (20.8%), p &lt; 0.001], and untreated patients overall were more likely to be older, have more comorbidities (SCLC only), and have Medicare, Medicaid or no insurance. Stage at diagnosis was also a factor but differed based on histology. NSCLC stage III and stage IV patients had higher odds of being untreated compared to stage I (Stage III OR: 2.91, 95% CI: 2.57-3.28; Stage IV OR: 4.82, 95% CI: 4.29-5.41) where these odds in SCLC patients were non-significant (Stage III OR: 0.94, 95% CI: 0.56-1.55) or lower (Stage IV OR: 1.61, 95% CI: 1.01-2.55). SCLC patients also had lower odds of delayed treatment (defined as &gt; 4 weeks to treatment) in stage III and stage IV compared to stage I (Stage III OR: 0.33, 95% CI: 0.23-0.48; Stage IV OR: 0.27, 95% CI: 0.20-0.38). Conclusions: This study shows an overall significant number of untreated lung cancer patients with treatment being strongly associated with insurance status, histology and stage at diagnosis. SCLC patients are more likely to be treated than NSCLC, and advanced stage is less a factor in treating SCLC than NSCLC. The difference may be due to the more aggressive nature of SCLC with physicians feeling more urgency to treat SCLC given its rapid progression and chemotherapy sensitivity compared to NSCLC.
Geographic distribution of clinical trials for breast cancer across the United States, 2011-2015.
Authors: Sindhu Janarthanam Malapati, Sunny R K Singh, Rohit Kumar, Jibran Ahmed, Vatsala Katiyar, Ishaan Vohra
Journal: Journal of Clinical Oncology (2019)

140 Background: Access to clinical trials is paramount for delivery of high quality cancer care. We aim to study the geographical distribution of phase 3 &amp; 4 clinical trials for females with breast cancer across 51 states between 2011 &amp; 2015. Methods: We searched Clinicaltrials.gov registry for phase 3 &amp; 4 clinical trials in US for females with breast cancer &amp; those first posted from 01/01/2011 to 12/31/2015. New cases of female breast cancer from 2011 to 2015 were estimated with U.S. Cancer Statistics Data Visualizations Tool (www.cdc.gov/cancer/dataviz). Results: We found 88 phase 3 &amp; 4 clinical trials over 51 states. The average number (no.) of new cancer cases and no. of trials per state were 22,985 and 34.4 (range: 16 - 57) respectively. On average, each state had 0.003 (SD: 0.002) trials per case. States with maximum number of cases and trials were California, New York, Texas and Florida. These accounted for 30.7% of total cases, but only 12.5% of total trials. Also, these four states had the lowest no. of clinical trials per case while District of Columbia had the highest (0.0123). The states with the lowest no. of clinical trials included Rhode Island, Vermont, Wyoming &amp; Alaska (3.7% of total trials). Table with data regarding states with lowest and highest cancer burden is attached. Conclusions: For breast cancer in females during the years 2011 to 2015, the ratio of available phase 3 &amp; 4 clinical trials to new cancer cases was quite low when examined state-wise. The gap widened as the cancer burden increased resulting in the lowest no. of clinical trials per case in the states with maximum cancer burden. This highlights the need of better allocation of resources and efforts across the nation when conducting clinical trials. [Table: see text]
Determination of Anti-Factor VIIII Antibody Titers, Isotypes and Epitopes by SPR Analysis of Human Plasma
Authors: Kenneth B Lewis, Phuong-Cac Nguyen, Jason T. Schuman, Christopher E. Walsh, Neil C. Josephson, Tom E. Howard, Dana C. Matthews, Nigel S. Key, Kathleen P. Pratt
Journal: Blood (2011)
Improving physical performance through independent, home-based exercise program prior to cancer-related surgery.
Authors: Rhodora C. Fontillas, An Ngo-Huang, Amy Ng, Roan Asumbrado, Betty Holder, Janet L. Williams, Josephine Bianty, Brent Braveman, Ki Shin, Eduardo Bruera
Journal: Journal of Clinical Oncology (2019)

54 Background: Surgery in older adults is a physiologically stressful event associated with reduced functional capacity and decreased quality of life. Poor preoperative performance is linked to risk of postoperative complications and prolonged functional recovery. The goal of this study is to determine the efficacy of an independent, home-based exercise program in improving physical performance prior to cancer-related surgery. Methods: Retrospective study of 217 consecutive patients referred for comprehensive prehabilitation including physical medicine and rehabilitation physician and physical therapy visits prior to intended oncologic surgery. Physical performance was assessed at consultation (baseline) and at the preoperative follow up visit in physical therapy. Physical performance measures included Six-Minute Walk test (6MWT), Five Times Sit to Stand (5xSTS), hand grip strength (HGS), gait speed (GS), and Timed Up and Go (TUG). Results: Median (IQR) age was 71 (64,77). The most common primary cancer diagnoses were gastrointestinal (43%), genitourinary (15%), breast (9%), and sarcoma (7%). 144 of the 217 (66%) underwent surgery and of these, 75 (52%) completed preoperative functional measures during their physical therapy follow-up. For the entire cohort of 217 patients, baseline median (IQR) measures included: 6MWT distance was 357 (193.3, 420) meters, 5xSTS was 12 (9.1, 16.3) seconds, right HGS was 43.3 (30.0, 58.3) pounds, GS was 1.4 (1, 1.7) meters per second, and TUG was 8.6 (7.3, 12.2) seconds. There were similar baseline physical function results in the cohort who completed preoperative measures. During the preoperative period (from baseline to pre-surgery visit), there was significant improvement in the 6MWT ( P=0.003), 5xSTS ( P=0.000), and TUG ( P=0.027). There was no significant change in HGS or GS. Conclusions: At baseline, most patients had major functional impairment, especially decreased submaximal exercise capacity. With the independent, home-based exercise prehabilitation program, patients had significant improvement in physical performance. Prehabilitation should be further investigated in these patients.
Comparison of Subcutaneous Injection Versus Intravenous Infusion of Cytarabine for Induction Therapy in Acute Myeloid Leukemia: Results of a Prospective, Randomized, Multicenter, Noninferiority Phase 3 Trial
Authors: Jie Jin, Zhou Jianfeng, Jianyong Li, Ying Lu, Jianping Shen, Chunyan Ji, Xiaoping Xu, Kang Yu, Hanyun Ren, Yan Li
Journal: Blood (2017)
Ubiquitary Expressed Major Histocompatibility (MHC) Class I and Minor Histocompatibility Alloantigens (mHAg) Are No Relevant Targets For Graft-Versus-Tumor (GvT) Reactions In Mice After Allogeneic Bone Marrow Transplantation
Authors: Matthias Stelljes, Stella Robert, Karin Frebel, Corinna Opitz, Jennifer Urh, Claudia Dahrenmöller, Christine Baumgart, Jörn C. Albring, Carsten Müller-Tidow, Wolfgang E. Berdel
Journal: Blood (2013)
Pirfenidone Reverses Murine Chronic Graft Versus Host Disease
Authors: Jing Du, Ryan P Flynn, Katelyn Paz, Ante Vulic, Tara M. Robinson, Katie E Lineburg, Kelli P A Macdonald, Geoffrey R Hill, Jonathan S Serody, Ivan Maillard, Angela Panoskaltsis-Mortari, Timothy Schacker, Leo Luznik, Bruce R. Blazar
Journal: Blood (2016)
Effects of Hemostasis Correction on Vascular Remodeling and Synovial Gene Expression Changes in Mice after Induced Hemarthrosis
Authors: Esther J Cooke, Jenny Y Zhou, Tine Wyseure, Srila Gopal, John Shimashita, Chanond A Nasamran, Kathleen M Fisch, Laurent O Mosnier, Annette von Drygalski
Journal: Blood (2018)
Response to: ‘Comment on: standardisation of myositis-specific antibodies: where are we today?’ by Infantino et al
Authors: Johan Rönnelid, Fabricio Espinosa-Ortega, Ingrid E Lundberg
Journal: Annals of the Rheumatic Diseases (2019)

We agree with the notions made by Infantino et al 1 in their reply to our previously published report2 concerning the need for multicentre studies to obtain large enough number to validate new methods for detection of myositis-specific antibodies (MSA) and myositis-associated autoantibodies (MAA). We also …
Epidemiological and economic evaluation of breast cancer screening in urban population in China: a multitarget calibrated modelling study
Authors: Le Wang, Ju-Fang Shi, Qing-Na Li, Juan Zhu, Zhong-Zhao Wang, Jing Li, Juan Yin, Hui-Yao Huang, Fang-Zhou Bai, Jian-Song Ren, Yi Fang, Ya-Na Bai, Xian-Zhen Liao, Ni Li, Bing-Zhao Li, Wan-Qing Chen, Min Dai
Journal: The Lancet (2019)
Care coordination for oral oncolytics through pharmacy integration and cycle 1-day 1 documentation.
Authors: Nancy Walker Peacock, Stacey McCullough, Jared Crumb, Leah Owens, Laura Kaufman, Edward Arrowsmith, Jeffrey Patton, Jack L. Taylor, Aaron J. Lyss, Carolyn J. Kelsey, Kimberly Senneke, Susan A Frailley
Journal: Journal of Clinical Oncology (2019)

260 Background: The growing number of oral oncolytic therapies (OOTs) necessitates a standardized EMR workflow that integrates pharmacy activities for dispense and patient management and standardizes cycle-1/day-1 (C1D1) documentation. Our practice’s treatment plans contain appropriately timed OOT follow-up activities including labs, physician follow-up visits, and pharmacy calls for toxicity and adherence checks, however complications in prescription fulfillment such as prior authorization, co-pay assistance, or inability of in-practice pharmacy to dispense limit the predictability of C1D1 dates of OOTs. Methods: An EMR query identified patients at a single clinic location of 5-medical oncologists (MDs) for whom oral oncolytic treatment plans were entered from January 1 to June 30, 2018. C1D1 date entered by the MD in the EMR was compared to the pharmacy processing system dispense date. Ten patients were identified, and 10% (1/10) had an accurate C1D1 documented within the EMR. As part of the ASCO Quality Training Program, to improve the accuracy of C1D1 documentation, a new workflow was implemented whereby: (1) a “hold” activity was added to new EMR treatment plans so that C1D1 remained pending until patients had received medication; (2) clinic checkout staff provided patients with information on the in-practice pharmacy and expectations for next steps; (3) pharmacists utilized existing reporting tools to identify newly entered treatment plans and transcribed orders into e-prescriptions sent to our practice pharmacy; (4) the pharmacy workflow ensued with pharmacy staff leading patient engagement, drug counseling; (5) pharmacists confirm C1D1, document within EMR (6) subsequent treatment plan activities were scheduled. Results: Following education and process changes within the clinic and pharmacy, accurate C1D1 documentation occurred in 90% (9/10) of patients initiating OOTs. Conclusions: Including pharmacy fulfillment time in EMR workflow can improve C1D1 documentation accuracy and associated management of OOTs. Education regarding roles and processes of prescribing MDs, pharmacy staff and clinic staff will be required to scale this process improvement throughout the organization.
Implications of gendered behaviour and contexts for social mobility in the USA: a nationally representative observational study
Authors: Benjamin W Domingue, Beniamino Cislaghi, Jason M Nagata, Holly B Shakya, Ann M Weber, Jason D Boardman, Gary L Darmstadt, Kathleen Mullan Harris
Journal: The Lancet Planetary Health (2019)

BackgroundWe constructed measures of an individual's gendered behaviour and their gendered environment to investigate the salience of gender norms during adolescence for social mobility during the next decade of life.MethodsIn this nationally representative observational study, we collected individual-level data from the National Longitudinal Study of Adolescent to Adult Health (Add Health), which enrolled a cohort of nationally representative school students aged 11–19 years from across the USA and followed them up for 14 years (ie, to age 25–33 years). We characterised gendered behaviour for adolescents in a performative sense via self-reports of behaviours and beliefs. We aggregated this individual-level measure to create a proxy measure of an individual's social context by taking averages for an individual's peers of the same sex and school year.FindingsBetween Jan 5, 1994, and Dec 26, 1995, Add Health collected data on a cohort of 20 745 students. 14 540 respondents were followed-up 14 years later between April 3, 2007, and Feb 1, 2009, of whom 7722 (53·1%) were female. More masculine male respondents were downwardly mobile; they were enrolled in school for fewer years and were more likely to have lower status jobs than their less masculine same-sex school peers. More masculine male respondents were also more likely to have jobs in occupational categories with larger proportions of males than their same-sex school peers. Gendered behaviour was not predictive of future educational and occupational attainment for female respondents. Male adolescents in school years with more masculine same-sex peers than male adolescents in other school years also tended to have lower educational and occupational attainment than their male peers. Educational and occupational attainment in early midlife for female respondents was not affected by their gendered environment.InterpretationGender, when measured as a set of gender-distinct behaviours in adolescence, was associated with differential patterns of social mobility from adolescence to young adulthood. Moreover, variation in an individual's local gender norms has implications for subsequent socioeconomic attainment, especially for male adolescents. These findings have potential implications for observed health disparities.FundingBill & Melinda Gates Foundation.
Azacitidine Improves Outcome in Patients with MDS and AML with High Risk Cytogenetics - a Single Center Experience
Authors: Vidhya Murthy, Nilupulee Kapuge, Charalampos Kartsios, Joanne Ewing, Evgenia Xenou, Maria Kaparou, Elmoamly Shereef, Emmanouil Nikolousis
Journal: Blood (2018)
Experimental Modeling of Acute- and Chronic-GvHD By Xenotransplanting Human Donor PBMCs or Cord Blood CD34+ Cells (HSC) into NSG Mice
Authors: Ann E Lin, Sonia Reyes, Xiaoyu An, Sonia Reyes, Wenqing Yang, Derron Yu, Duan Dan, Henry Li
Journal: Blood (2018)
Abstract 745: Voluntary Late-life Exercise Attenuates Frailty and Improves Maladaptive Changes Associated With Cardiac Aging in Female Mice
Authors: Elise S Bisset, Susan E Howlett
Journal: Circulation Research (2019)

Voluntary aerobic exercise has many positive health benefits and may actually attenuate frailty. Exercise may also improve cardiac function in the setting of aging, although links between exercise, frailty and age-dependent cardiac remodeling are unclear. To investigate age-related effects of exercise, 21-23 month old female C57BL/6 mice were divided into two groups, an exercise group (n=9) and a sedentary group (n=9). Frailty was measured with a clinical frailty index (FI) tool, then mice were randomly assigned to either exercise or sedentary groups matched by their initial FI scores. The exercise group was allowed constant access to a running wheel for 13 weeks, while sedentary animals had no wheel access. Cardiac function was measured with echocardiography at baseline, midpoint (6 weeks) and endpoint (13 weeks) in both groups. FI scores increased with age in sedentary mice (0.18 ± 0.02 to 0.34 ± 0.05; baseline vs endpoint) but not in the exercise group (0.18 ± 0.02 to 0.20 ± 0.01) and this difference was significant (at endpoint; p&lt;0.05). Fractional shortening (FS) decreased with age in sedentary mice (34.81 ± 3.3% to 22.86 ± 5.5%; p&lt;0.05; at endpoint) but exercise protected hearts against this decline (34.64 ± 2.3% to 36.16 ± 3.1%). A similar pattern was seen with ejection fraction (EF) where EF deteriorated with age (63.28 ± 4.2% to 44.70 ± 9.2%; p&lt;0.05 at endpoint) but stayed similar in exercised animals (63.79 ± 3.6% to 65.74 ± 4.1%). Isovolumic relaxation time decreased with age in sedentary mice (20.43 ± 1.1 ms to 16.50 ± 1.7 ms; p&lt;0.05) but not in exercised mice (19.32 ± 1.1 ms to 16.80 ± 1.1 ms). In addition, left ventricular (LV) mass was actually smaller in the exercise group compared to the sedentary group at endpoint (138.4 ± 19 mg vs 211.6 ± 34 mg; p&lt;0.05). Interestingly, age-associated changes in EF, FS and LV mass at the endpoint were correlated with and closely graded by FI score in all mice (e.g. EF: r= 0.67, p&lt;0.05, FS: r=0.68, p&lt;0.05; LV mass: r=0.68, p&lt;0.05). These results show that voluntary exercise attenuates frailty and prevents negative signs of cardiac aging in older female mice. These data suggest that cardiac function is closely linked to overall health, quantified as frailty, and that late-life interventions to reduce frailty can improve heart health.