tbuckley/cabot-search huggingface dataset:
Abstract 223: Dynamic Multimodality Imaging Monitored Anti-inflammation Therapy for Myocardial Infarction: Exploring the Role of MCC950 in Murine Model
Authors: Xiang Li, Weidong Yang, Jing Wang
Journal: Circulation Research (2019)

Objectives: The aim of this study is applying non-invasive multimodality imaging to investigate the potential therapeutic effects of MCC950, a novel selective NLRP3 inflammasome inhibitor, in myocardial infarction (MI) model. Methods: C57BL/6 mice were subjected to the MI or Sham model. 18 F-FDG PET/CT was undertaken for monitoring any post-MI inflammation changes on days 1, 3, 5 and 7. 18 F-FDG PET/CT and echocardiography were both used to quantitate any alterations of infarct size and cardiac function on days 7 and 28 post-MI. Results: Dynamic 18 F-FDG PET/CT revealed that MI+MCC950 group had a lower accumulation of 18 F-FDG at infarct region as early as day one, and remained lower until day seven post-MI when compared to the MI group (Infarct/remote SUV mean ratios, from day 1 to 7 respectively: 2.37±0.11, 3.10±0.28, 2.74±0.43, 1.89±0.26, P &lt; 0.05.). What’s more, MCC950 inhibited infarct size expanding on day 7 (31.90±1.60% vs 36.30±3.31%, P &lt; 0.05 vs MI group). The use of echocardiography suggested that MCC950 treatment increased ejection fraction (EF) and fraction shortening (FS), (EF: 48.72±3.86% vs 39.64±2.85%, P &lt; 0.05; FS: 22.93±2.58% vs 17.54±1.91%, P &lt; 0.05), meanwhile decreased end-diastolic volume (EDV) and end-systolic volume (ESV) when compared with that in the MI group on day 28 (EDV: 70.91±3.31 vs 82.40±5.30 ul, P &lt; 0.05; ESV: 38.95±4.38 vs 50.29±3.76 ul, P &lt; 0.05). Conclusions: MCC950 reduced inflammatory response, infarct size and preserved cardiac function post-MI. Dynamic multimodality imaging may be potential approaches for basic research and future clinical translation in the use of anti-inflammation therapy for MI.
Advances in clinical trial design for development of new TB treatments—Translating international tuberculosis treatment guidelines into national strategic plans: Experiences from Belarus, South Africa, and Vietnam
Authors: Grania Brigden, Nguyen Viet Nhung, Alena Skrahina, Norbert Ndjeka, Dennis Falzon, Matteo Zignol
Journal: PLoS Medicine (2019)

The World Health Organization (WHO) plays an important role in setting global norms and standards with a focus on public health and publishes international guidelines regularly to support Member States, particularly ministries of health, in the provision of the highest standard of healthcare.• Over the last 5 years, multiple advances in diagnosis and treatment of tuberculosis (TB) have resulted in a number of new WHO guidelines for TB care, but these recent guidelines have not always been implemented in a timely fashion, raising issues in their adoption and scale-up at country level.• We discuss the experiences of three countries with a high burden of multidrug-resistant TB (MDR-TB)-Belarus, South Africa, and Vietnam-in implementing recent WHO guidelines on bedaquiline, a drug recently registered and recommended for the treatment of MDR-TB and the standardised shorter treatment regimen (STR) for MDR-TB.• The process of adopting and implementing new guidelines requires national TB programmes (NTPs) to interact with multiple agencies: both intergovernmental departments and external agencies such as regulators and donors.These processes are country specific, but there are some generalised challenges that NTPs in high-burden countries experienced when implementing recent WHO MDR-TB guidance.• With multiple trials of new regimens for MDR-TB and new classes of drugs in the clinical treatment pipeline, the frequency of new guidelines for TB is expected to increase, and it is important to support NTPs to implement and scale-up these new developments in treatment.
Severe Aplastic Anemia (SAA) in Colombia: Characteristics and Treatment in 6 Centers
Authors: Virginia Abello, Claudia Sossa, Paola Omaña, Kenny Mauricio Galvez, Carlos Alberto Pardo, Monica Osuna, Angela María Peña, Luis Antonio Salazar, Sara Ines Jimenez, Maria Helena Solano, Claudia Patricia Casas, Espinosa Daniel, Mauricio Chaparro, Adriana Linares, Marcela Estupiñan, Bonell Patiño, Josef T. Prchal
Journal: Blood (2018)
The Outcomes of Epstein-Barr Virus Specific T Cells from Different Sources for EBV Infections in Recipients of Allogeneic Stem Cell Transplantation
Authors: Ren Lin, Fen Huang, Zhiping Fan, Xiaoyan Shao, Guoxian Dai, Na Xu, Li Xuan, Jieyu Ye, Jing Sun, Qifa Liu
Journal: Blood (2018)
Precision screening for familial hypercholesterolaemia: a machine learning study applied to electronic health encounter data
Authors: Kelly D Myers, Joshua W Knowles, David Staszak, Michael D Shapiro, William Howard, Mrinal Yadava, David Zuzick, Latoya Williamson, Nigam H Shah, Juan M Banda, Joe Leader, William C Cromwell, Ed Trautman, Michael F Murray, Seth J Baum, Seth Myers, Samuel S Gidding, Katherine Wilemon, Daniel J Rader
Journal: The Lancet Digital Health (2019)

BackgroundCardiovascular outcomes for people with familial hypercholesterolaemia can be improved with diagnosis and medical management. However, 90% of individuals with familial hypercholesterolaemia remain undiagnosed in the USA. We aimed to accelerate early diagnosis and timely intervention for more than 1·3 million undiagnosed individuals with familial hypercholesterolaemia at high risk for early heart attacks and strokes by applying machine learning to large health-care encounter datasets.MethodsWe trained the FIND FH machine learning model using deidentified health-care encounter data, including procedure and diagnostic codes, prescriptions, and laboratory findings, from 939 clinically diagnosed individuals with familial hypercholesterolaemia (395 of whom had a molecular diagnosis) and 83 136 individuals presumed free of familial hypercholesterolaemia, sampled from four US institutions. The model was then applied to a national health-care encounter database (170 million individuals) and an integrated health-care delivery system dataset (174 000 individuals). Individuals used in model training and those evaluated by the model were required to have at least one cardiovascular disease risk factor (eg, hypertension, hypercholesterolaemia, or hyperlipidemia). A Health Insurance Portability and Accountability Act of 1996-compliant programme was developed to allow providers to receive identification of individuals likely to have familial hypercholesterolaemia in their practice.FindingsUsing a model with a measured precision (positive predictive value) of 0·85, recall (sensitivity) of 0·45, area under the precision–recall curve of 0·55, and area under the receiver operating characteristic curve of 0·89, we flagged 1 331 759 of 170 416 201 patients in the national database and 866 of 173 733 individuals in the health-care delivery system dataset as likely to have familial hypercholesterolaemia. Familial hypercholesterolaemia experts reviewed a sample of flagged individuals (45 from the national database and 103 from the health-care delivery system dataset) and applied clinical familial hypercholesterolaemia diagnostic criteria. Of those reviewed, 87% (95% Cl 73–100) in the national database and 77% (68–86) in the health-care delivery system dataset were categorised as having a high enough clinical suspicion of familial hypercholesterolaemia to warrant guideline-based clinical evaluation and treatment.InterpretationThe FIND FH model successfully scans large, diverse, and disparate health-care encounter databases to identify individuals with familial hypercholesterolaemia.FundingThe FH Foundation funded this study. Support was received from Amgen, Sanofi, and Regeneron.
Lost productivity and time in patients with metastatic breast cancer receiving treatment.
Authors: Stacey A. Ingram, Courtney Williams, Aidan Gilbert, Valerie Lawhon, Jasmine D. Davis, Clara Wan, Kendal Dekle, Janel Lowman, Jonathan Jones, Gabrielle Betty Rocque
Journal: Journal of Clinical Oncology (2019)

106 Background: Costs for cancer patients are not all monetary. For patients with limited life expectancy, such as metastatic breast cancer (MBC) patients, time spent in the hospital or clinic setting can become burdensome. The goal was to evaluate time spent on healthcare among patients receiving treatment for MBC. Methods: This survey-based, cross-sectional study included women ≥18 years with MBC who received treatment at two academic medical centers in Alabama from 2017-2019. Questions regarding employment status, MBC-related hours missed from work, and time spent on healthcare-related activities were used to quantify lost productivity and time. Descriptive statistics included means and standard deviations (SD) or medians and interquartile ranges (IQR) for continuous variables and frequencies for categorical variables. Effect sizes were calculated using Cohen’s d or Cramer’s V. Results: We surveyed 83 female MBC patients with a median age of 59 years (IQR 50-66). Among all respondents, 34% were African American, 41% held a college degree, and 52% had a household income of &lt; $40,000. Patients spent a median 60 minutes (IQR 30-110) traveling from their home to clinic and a median 120 minutes (IQR 60-180) receiving care at a clinic visit. Though not statistically significant, modest differences were found for patients with differing insurance types in travel time. Patients with Medicare had the shortest travel time (median 45 minutes [IQR 30-75]) compared to Medicaid (60 minutes [IQR 60-80]) and private insurance (60 minutes [IQR 30-120]; d = .06).). Patients spent a median 30 minutes (IQR 0-60) on cancer care related activities outside of a clinic visit. Most patients were retired (31%); however, 15% worked full-time, 6% worked part-time, and 20% were on disability. For working women, a median of 8 hours (IQR 1-11) were missed from work in the week. Conclusions: This study highlights productivity losses uncaptured by current patient healthcare cost calculations. Further work is needed to identify and minimize these additional patient costs related to lost productivity during cancer treatment.
Abstract 253: Pharmacological and Genetic Inhibition of Transient Receptor Potential Canonical 6 (TRPC6) as a Novel Treatment for Heart Failure and Duchenne Muscular Dystrophy (DMD) Pharmacological and Genetic Inhibition of Transient Receptor Potential Canonical 6 (TRPC6) as a Novel Treatment for Heart Failure and Duchenne Muscular Dystrophy (DMD)
Authors: Brian L Lin, Sumita Mishra, Grace K Muller, Djahida Bedja, Guangshuo Zhu, Jinying Yang, Mark E Anderson, Steve S Pullen, David A Kass
Journal: Circulation Research (2019)

Intro: Duchenne muscular dystrophy (DMD) patients suffer from spinal deformities (scoliosis and kyphosis) and die prematurely in their thirties, mostly due to heart disease. DMD is caused by the lack of the dystrophin protein, but calcium overload contributes to pathology as a secondary insult. Inhibiting hyperactive calcium channels in DMD, such as TRPC6, is a novel therapeutic strategy for treating DMD, and we test the efficacy of pharmacological and genetic TRPC6 inhibition in vivo . Therefore, my objectives are: 1) determine the efficacy of chronic pharmacological TRPC6 inhibition in heart disease 2) determine the therapeutic efficacy of genetic TRPC6 inhibition in DMD and 3) identify novel mechanisms of TRPC6 hyperactivity. Results: 1) Using pressure-overloaded mice as our model of heart disease, we applied the first and only-known TRPC6 inhibitor (BI 749327, 30 mg/kg/day) that is both specific and bioavailable. Chronic pharmacological TRPC6 inhibition blunted a pathological calcineurin/NFAT-TRPC6 feedforward signaling pathway in vivo , resulting in improved fractional shortening, normalized cardiac hemodynamics, and potently reduced fibrotic signaling and fibrosis. 2) We generated dystrophin-utrophin-deficient mice, or double-knock-out (DKO) mice, a severe model of DMD that exhibits muscle weakness, spinal deformities, and premature death at ~8 weeks of age. We also generated dystrophin-utrophin-TRPC6-deficient mice, or triple-knock-out (TKO) mice, which exhibited dramatically improved kyphosis, striated muscle function, and nearly three-fold improvement in lifespan. 3) We demonstrate CaMKII mediates TRPC6-mediated contractility combining a custom cardiomyocyte stretch assay with pharmacological and genetic inhibition of TRPC6 and CaMKII. Conclusion: TRPC6 inhibition potently reduces fibrosis in heart disease, and dramatically improves life expectancy in DMD. CaMKII is a novel TRPC6-activating kinase, necessary for TRPC6-mediated mechanosensitive activation and force response. The striking therapeutic effects of TRPC6 inhibition in disease may be due to interruption of a kinase imbalance in which CaMKII hyperactivates TRPC6. Future studies will determine the efficacy of pharmacological TRPC6 inhibition in DMD.
Pre-Transplant Serum Beta-2 Microglobulin Level Is a Potential Novel Prognostic Marker for Overall Survival after Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Naonori Harada, Takahiko Nakane, Mika Nakamae, Hiroshi Okamura, Satoru Nanno, Mitsutaka Nishimoto, Yasunobu Takeoka, Asao Hirose, Yasuhiro Nakashima, Hideo Koh, Masayuki Hino, Hirohisa Nakamae
Journal: Blood (2018)
Practical Utilisation of Octapharma FVIII Concentrates in Previously Untreated and Minimally Treated Haemophilia a Patients Entering Routine Clinical Treatment with Nuwiq®, Octanate® or Wilate® — the Protect-NOW Study
Authors: Johannes Oldenburg, Anna Pavlova, Susan Halimeh, Robert Klamroth, Joris Versteden, Martina Jansen, Larisa Belyanskaya
Journal: Blood (2018)
Ultimate Outcomes of Patients with Recurrent Diffuse Large B Cell Lymphoma Who Do Not Respond to Second-Line Chemotherapy
Authors: Rebecca Elstrom, Peter Martin, Katya Ostrow, Jacqueline Barrientos, Richard R. Furman, Jia Ruan, Michael Schuster, Tsiporah Shore, Amy Chadburn, Morton Coleman, John P. Leonard
Journal: Blood (2008)
Expressions of KLF1, FOXO3a, HOOK3 and MIER1 genes Are Associated with Fetal Hemoglobin Levels in Hereditary Persistence of Fetal Hemoglobin,
Authors: Fernanda Marconi Roversi, Anderson Ferreira Cunha, Ana Flavia Brugnerotto, Regiane Ferreira, Dulcinéia Martins Albuquerque, Carolina Lanaro, Joao Machado-Neto, Sara T. Olalla-Saad, Fernando Ferreira Costa
Journal: Blood (2011)
FDG and FCH PET/CT of Multiple Myeloma at Various Clinical Situations: Lesion Detection, Proposal for a Patient-Based "Summ" Score and Reproducibility of Scoring
Authors: Jules Zhang-Yin, Sona Balogova, Mor Seny Gueye, Mohamad Mohty, Françoise Montravers, Jean Noel Talbot, Laurent Garderet
Journal: Blood (2018)
Decreased Physical Working Capacity in Adolescents With Nonalcoholic Fatty Liver Disease Associates With Reduced Iron Availability
Authors: Tim Mitchell, Elizabeth McKinnon, Oyekoya Ayonrinde, Leon A. Adams, Debbie Trinder, Anita C.G. Chua, Robert U. Newton, Leon Straker, John K. Olynyk
Journal: Clinical Gastroenterology and Hepatology (2019)
Development of a time to treatment metric across an NCI designated academic health system.
Authors: Maya L Najarian, Pooja Shaw, Kimberly M Severino, James Hamrick, Kerin B. Adelson
Journal: Journal of Clinical Oncology (2019)

307 Background: Time to treatment (TTT) is an important quality metric as shorter times improve patient satisfaction and retention, overall survival, as well as reduce distress. Multiple factors can lengthen TTT including provider availability, biopsy, pathology review, assembly of medical records, multidisciplinary care coordination, staging studies, and patient preference. No national benchmarks exist for TTT, however one large health system noted baseline TTT (indexed on diagnosis date) of 29d for internally diagnosed and 41d for externally diagnosed patients ( Khorana &amp; Bolwell, NEJM Catalyst, 2019 ). Limited guidance exists on how best to measure TTT for cancer patients across an institution. Methods: We developed a consistent TTT metric across Yale’s Smilow Cancer Hospital, comprised of an academic hub and community practices, using data obtained from Flatiron Health’s EHR-derived de-identified database, with disease team assigned for each provider. Qualifying patients had a new patient visit between Jan - Dec 2018, and scheduled treatments from Jan 2018 - Mar 2019. We defined TTT as calendar days from the first qualifying visit to the sooner of either an IV antineoplastic administration or interventional surgery. Results: The population sample included 1,090 patients seen by five disease teams. 558 (51%) patients had a qualifying intervention. The overall median TTT was 26d (IQR14 - 44). The median TTT for IV antineoplastic administration was 24d (IQR 14 - 43). The median TTT for interventional surgery was 27d (IQR 15 - 45). The median TTT by disease team: Breast 24d (IQR 14 - 38), GI 24d (IQR13 - 36), Head &amp; Neck 27d (IQR 15 - 40), Hematology 35d (IQR 11 - 76), and Thoracic 28d (IQR 16 - 51). Conclusions: Evaluating TTT across an institution can help identify opportunities for practice improvements. We hypothesize that recurring delivery of this metric will enable assessment and benchmarking of quality improvement interventions. Future work will focus on improving this measure by incorporating additional cancer treatments (e.g. radiation therapy), and development of interventions to shorten TTT at our center.
NICE updates antidepressant guidelines to reflect severity and length of withdrawal symptoms
Authors: Gareth Iacobucci
Journal: BMJ (2019)

The National Institute for Health and Care Excellence has amended its guidelines1 on depression to recognise the severity and length of antidepressant withdrawal symptoms.

The guidance on treating depression in adults now states that withdrawal symptoms may be severe and protracted in some patients.

NICE’s previous guideline, which was originally published in 2009 and updated last year, said that withdrawal symptoms are “usually mild and self limiting over about one week.”2

But in an amendment, NICE acknowledges that …
Changes of family structure and treatment status of people with severe mental illness in rural China: a comparative study from 1994 to 2015
Authors: Mao-Sheng Ran, Man-Man Peng, Yue-Hui Yu, Tian-Ming Zhang, Wei Luo, Shi-Hui Hu, Xin Yang, Chang-Cheng Liu, Bo Liu, Ke-Zhi Liu, Ke Gong, Chao-Hua Huang, Tin Zhang, Wei-Hong Kuang, Cecilia Lai-Wan Chan, Meng-Ze Xiang
Journal: The Lancet (2019)
Hematological Cancer Consortium: Multi-Center Acute Lymphoblastic Leukemia Registry Data from India
Authors: Anu Korula, Jina Bhattacharyya, Hasmukh Jain, Rajan Kapoor, Chepsy C Philip, Maitreyee Bhattacharyya, Nikita Mehra, Smita Kayal, Dinesh Bhurani, Linu Jacob, Ranjit Kumar Sahoo, Gaurav Prakash, Om Prakash, Thenmozhi Mani, Jeyaseelan Lakshmanan, Biju George, Bhausaheb Bagal, Satyaranjan Das, Venkatraman Radhakrishnan, Prasanth Ganesan, Vikram Mathews, Manju Sengar
Journal: Blood (2018)
Variants in ARID5B Gene Are Associated with the Development of Acute Lymphoblastic Leukemia in Mexican Children
Authors: Adriana Reyes-León, Diana Fernández-García, Maribel Ramírez-Martínez, David Amaro-Muñoz, José Antonio Velázquez-Aragón, Consuelo Salas-Labadía, Marta Zapata-Tarres, Liliana Velasco-Hidalgo, Norma Lopez-Santiago, Mayra Ivette López-Ruíz, Mónica Anabell Malavar-Guadarrama, Rocio Cardenas-Cardos, Rogelio Alejandro Paredes-Aguilera, Michael Dean, Roberto Rivera-Luna, Patricia Perez-Vera
Journal: Blood (2018)
Primary IMiD Refractory Myeloma; Results from 3894 Patients Treated in the Phase III Myeloma XI Study
Authors: Charlotte Pawlyn, Faith E Davies, Martin F Kaiser, David A Cairns, Alina Striha, Corinne Collett, Anna Waterhouse, John R Jones, Bhuvan Kishore, Mamta Garg, Cathy D Williams, Kamaraj Karunanithi, Jindriska Lindsay, Matthew W Jenner, Gordon Cook, Mark T Drayson, Roger G Owen, Nigel H Russell, Walter M Gregory, Graham H Jackson, Gareth J Morgan
Journal: Blood (2016)
Clinicogenomic Radiotherapy Classifier Predicting the Need for Intensified Locoregional Treatment After Breast-Conserving Surgery for Early-Stage Breast Cancer
Authors: Martin Sjöström, S. Laura Chang, Nick Fishbane, Elai Davicioni, Shuang G. Zhao, Linda Hartman, Erik Holmberg, Felix Y. Feng, Corey W. Speers, Lori J. Pierce, Per Malmström, Mårten Fernö, Per Karlsson
Journal: Journal of Clinical Oncology (2019)

PURPOSE Most patients with early-stage breast cancer are treated with adjuvant radiotherapy (RT) after breast-conserving surgery (BCS) to prevent locoregional recurrence (LRR). However, no genomic tools are used currently to select the optimal RT strategy. METHODS We profiled the transcriptome of primary tumors on a clinical grade assay from the SweBCG91-RT trial, in which patients with node-negative breast cancer were randomly assigned to either whole-breast RT after BCS or no RT. We derived a new classifier, Adjuvant Radiotherapy Intensification Classifier (ARTIC), comprising 27 genes and patient age, in three publicly available cohorts, then independently validated ARTIC for LRR in 748 patients in SweBCG91-RT. We also compared previously published genomic signatures for ability to predict benefit from RT in SweBCG91-RT. RESULTS ARTIC was highly prognostic for LRR in patients treated with RT (hazard ratio [HR], 3.4; 95% CI, 2.0 to 5.9; P &lt; .001) and predictive of RT benefit ( P interaction = .005). Patients with low ARTIC scores had a large benefit from RT (HR, 0.33 [95% CI, 0.21 to 0.52], P &lt; .001; 10-year cumulative incidence of LRR, 6% v 21%), whereas those with high ARTIC scores benefited less from RT (HR, 0.73 [95% CI, 0.44 to 1.2], P = .23; 10-year cumulative incidence of LRR, 25% v 32%). In contrast, none of the eight previously published signatures were predictive of benefit from RT in SweBCG91-RT. CONCLUSION ARTIC identified women with a substantial benefit from RT as well as women with a particularly elevated LRR risk in whom whole-breast RT was not sufficiently effective and, thus, in whom intensified treatment strategies such as tumor-bed boost, and possibly regional nodal RT, should be considered. To our knowledge, ARTIC is the first classifier validated as predictive of benefit from RT in a phase III clinical trial with patients randomly assigned to receive or not receive RT.
Abstract 476: Pharmacogenetics and Drug Discovery for Anthracycline-Induced Cardiotoxicity Enabled by Sinoatrial Node-like Cells Derived From Human Pluripotent Stem Cells
Authors: Shuibing Chen
Journal: Circulation Research (2019)

The sinoatrial node (SAN) is the primary pacemaker of the heart. The human SAN is poorly understood due to limited primary tissue access and lack of robust in vitro derivation methods. We developed an efficient strategy, using a dual SHOX2:GFP; MYH6:mCherry knock-in reporter line, to generate and purify human pluripotent stem cell-derived SAN cells (hPSC-SAN), displaying molecular and electrophysiological characteristics of bona-fide nodal cells. We modeled cell type specific toxicity upon treatment with doxorubicin (DOXO) using hPSC-SAN generated from a library of induced pluripotent stem cells (iPSCs). We discovered 3 new genetic loci associated with increased sensitivity to DOXO-induced hPSC-SAN death. Genetic variants in these loci were associated with significantly higher early arrhythmia risk in patients receiving DOXO, confirmed by an unbiased PheWAS analysis. Finally, the in vitro DOXO assay enabled an unbiased drug screening platform and identification a candidate therapeutic that can partially block DOXO-mediated cardiac toxicity.
Integrating Phosphoproteomics and Transcriptional Classifiers Reveals "Hidden Signaling" in Multiple Myeloma Including Differential KRAS and NRAS Mutant Effects
Authors: Yu-Hsiu T. Lin, Gergory P. Way, Margarette C. Mariano, Makeba Marcoulis, Ian Ferguson, Casey S. Greene, Arun P Wiita
Journal: Blood (2018)
Gain of the Short Arm of Chromosome 2 Is a New Recurring Chromosome Aberration in CLL Which Is Significantly Associated with an Unmutated IgGVH Status and a Complex Aberrant Karyotype and Leads to a Higher Expression of Genes Located on 2P.
Authors: Claudia Haferlach, Sonja Rauhut, Sylvia Merk, Frank Dicker, Susanne Schnittger, Wolfgang Kern, Martin Dugas, Torsten Haferlach
Journal: Blood (2007)