tbuckley/cabot-search huggingface dataset:
Partnership with an independent genetic counselor and standardized screening: Effect on the identification, referral, and genetic testing of eligible patients in a community oncology clinic.
Authors: Larry Edward Bilbrey, Natalie R. Dickson, Smita K Rao, Gregg Christian Shepard, Kathy McGee, Susan A Frailley, Stacey L Poole, Jeffrey Patton
Journal: Journal of Clinical Oncology (2019)

138 Background: A nine provider, community oncology clinic had limited local access to genetic counseling. Additionally, the practice had no process for identifying appropriate patients for genetic counseling or testing and no method to track referrals and test results. The practice partnered with a contracted genetic counselor and a study was completed to standardize screening and follow-up and to increase referrals and testing. Methods: Baseline data on genetic testing performed in 2018 was obtained from three major genetic testing labs. Based on the NCCN guidelines for genetic assessment, the practice created automated screening reports from the EMR, supplemented by manual chart review, to identify appropriate patients for genetic counseling. Front office, clinical and billing workflows were created. Patients were scheduled to see the counselor via in-person appointments or remotely via a HIPAA compliant telemedicine platform. The genetic counseling sessions included education and consent for testing followed by review and discussion of results. Consultations and genetic testing results were documented in the practice’s EMR. Results: Baseline data showed that the clinic tested 7 patients in 2018; 2 patients in the first quarter. During the pilot from Jan-Mar 2019, 34 patients were referred for genetic counseling; 30 consented to testing. This is a 329% increase over 2018; 1400% for the first quarter. Of the 30 patients tested during the pilot, 6 were positive for a pathogenic mutation. Conclusions: By contracting with a genetic counselor, and establishing procedures for screening, counseling, consenting, testing and follow-up, the practice was able to increase the number of appropriate genetic testing considerably. This process will be scaled to multiple sites of a community practice.
Observations from the First 1,000 Suspected aHUS Patients, Tested By a Rapid aHUS Genetic (NGS) Panel: Causative Genes Identified in a Subpopulation of Our Database
Authors: James Anderson-Furgeson, Jamey Kain, Sujatha Venkataramani, Jooeun Lim, Mike Ero, Bradley Lewis
Journal: Blood (2018)
Rituximab Combined with 3 Cycles of High Dose Dexamethasone Improves Response in Patients with Newly-Diagnosed, Persistent, and Chronic Immune Thrombocytopenia (ITP)
Authors: Rebecca L. Elstrom, Caroline Seery, Christina Moll, Allison Miller, Julia Gabor, Daniel Maffezzoli, Paul Andrew Basciano, Waleed Ghanima, James B Bussel
Journal: Blood (2012)
Treatment decision-making and financial toxicity in metastatic breast cancer.
Authors: Clara Wan, Courtney Williams, Stacey A. Ingram, Valerie Lawhon, Jennifer Young Pierce, Kendal Dekle, Janel Lowman, Jonathan Jones, Andres Azuero, Aidan Gilbert, Gabrielle Betty Rocque
Journal: Journal of Clinical Oncology (2019)

97 Background: Shared decision-making (SDM), a process where patients partner with their physician to incorporate personal preferences into treatment decisions, is a tenet of high-value healthcare. It is unknown if high-value care associated with SDM manifests in the form of decreased out-of-pocket costs. Therefore, this study analyzes the relationship between patient preference for SDM and financial toxicity in metastatic breast cancer (MBC). Methods: This cross-sectional study utilized surveys of women age ≥ 18 with MBC who received care at two academic hospitals in Alabama between 2017 and 2019. SDM preference and financial toxicity were measured using the Control Preferences Scale and the Comprehensive Score for Financial Toxicity (COST) tool (11-item scale from 0-44, with lower scores indicating worse FT), respectively. Patient demographic and clinical data were abstracted from the electronic medical record. Effect sizes were calculated using Cohen’s d or Cramer’s V. Differences in financial toxicity by SDM preference were estimated using mixed models clustered by site and treating medical oncologist. Results: In 79 women with MBC, 41% preferred SDM, 33% preferred provider-driven decision making, and 22% preferred patient-driven decision making. Patients preferring SDM were more often college educated (48% vs. 40%; V = .15), higher income (52% vs. 44%; V = .09), and privately insured (47% vs. 41%; V = .11). Overall median COST score was 23 (interquartile range 16-30), which varied modestly by SDM preference. After adjusting for patient demographic and clinical characteristics, similar financial toxicity levels were found in patients who preferred SDM (COST 22, 95% confidence interval [CI] 19-25), patient-driven decision making (COST 22, 95% CI 18-26), and provider-driven decision making (COST 24, 95% CI 20-27). Conclusions: Similar levels of financial toxicity were found in patients with differing decision–making preferences regarding their MBC treatment, which may be secondary to lack of discussions about cost. Further research is needed to determine if and how financial toxicity is being identified or included within decision-making.
Leukocyte-specific siRNA delivery revealing IRF8 as a potential anti-inflammatory target
Authors: Nuphar Veiga, Meir Goldsmith, Yael Diesendruck, Srinivas Ramishetti, Daniel Rosenblum, Eran Elinav, Mark A. Behlke, Itai Benhar, Dan Peer
Journal: Journal of Controlled Release (2019)
Apoptotic and Non-Apoptotic Cellular Pathways Executed by Bortezomib (BTZ) in Rituximab-Resistant Lymphomas
Authors: Juan Gu, Francisco J. Hernandez-Ilizaliturri, Cory Mavis, Natalie M Czuczman, Karen E Thudium, George Deeb, John Gibbs, Myron S. Czuczman
Journal: Blood (2011)
A High-Throughput Workflow for the Detection, Isolation and Genomic Analysis of Single Circulating Multiple Myeloma Cells
Authors: Andrea Raspadori, Claudio Forcato, Petrini Edoardo, Francesca Marzia Papadopulos, Alberto Ferrarini, Valentina Del Monaco, Mario Terracciano, Carrie Morano, Steven Gross, Chiara Bolognesi, Genny Buson, Francesca Fontana, Mark Connelly, Cecilia Simonelli, Gianni Medoro, Nicolò Manaresi
Journal: Blood (2018)
Abstract 371: Chromatin Remodeling Mechanisms by Bromodomain PHD Finger Transcription Factor in Cardiac Hypertrophy and Heart Failure
Authors: Salma M Awad, Esra Zahid, Sarah Al-Shalan, Ayodele Alaiya, Qamar Al-Tinawi, Amar Al-Sheikh, Muhammed Kunhi, Kamar Al-Haffar, Jehad Al-Buraiki, Atli Eyjolsson, Waleed Al-Habib, Coralie I Poizat
Journal: Circulation Research (2019)

Alteration of chromatin conformation has a profound effect on gene expression, and can lead to heart failure, which remains a major cause of death worldwide. ATP-dependent chromatin remodelers utilize the energy of ATP to remodel chromatin in specific regions of the genome. However, the mechanisms of ATP-dependent chromatin remodeling and how they connect to the genome remain poorly understood. We have discovered that the nucleosome remodeler Bromodomain PHD-finger Transcription Factor (BPTF), the largest subunit of the Nucleosome Remodeling Factor (NURF), plays an important role in cardiac hypertrophy. Our preliminary data show that BPTF is enriched in failing human hearts, a phenomenon similarly observed in mouse hearts subjected to pressure overload hypertrophy (TAC). BPTF is up-regulated in primary neonatal rat ventricular myocytes (NRVM) and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) stimulated with the hypertrophic agonist phenylephrine (PE). Strikingly, specific silencing of BPTF in NRVM and hiPSC-CMs, inhibits the expression of the atrial natriuretic peptide (ANP), a marker of cardiac hypertrophy. Chromatin immunoprecipitation performed in NRVM show that BPTF binds to the ANP promoter, but not to GAPDH. Proteomics experiments performed in failing human hearts revealed a multi-protein complex formed between BPTF and novel chromatin regulators. At the level of the nucleosome, BPTF in combination with one of its partners, remodels chromatin by facilitating nucleosomes “sliding” along the DNA. This mechanism is mediated by the binding of BPTF to histone H3 trimethylated at Lysine-4 (H3K4me3), an “active” mark of transcription also up-regulated in the early phase of cardiac hypertrophy in NRVM and in mouse TAC hearts. Our study suggests a novel chromatin signature controlled by BPTF, that dictates specific gene patterns implicated in pathological cardiac hypertrophy. Our study uncovers a new epigenetic mechanism controlling pathological cardiac remodeling and heart failure.
A CIBMTR Prognostic Model for Progression-Free Survival (PFS) After Autologous Hematopoietic Cell Transplantation (AHCT) for Relapsed or Refractory Hodgkin Lymphoma (HL)
Authors: Theresa Hahn, Philip L. McCarthy, Jeanette Carreras, Mei-Jie Zhang, Hillard M. Lazarus, Ginna G. Laport, Silvia Montoto, David G. Maloney, Parameswaran Hari
Journal: Blood (2011)
Hyperbaric Oxygen Therapy Improves Post-Transplant Umbilical Cord Blood Engraftment
Authors: Omar S. Aljitawi, Xiao Yinghua, Tara Lin, Jeff Eskew, Nikhil Parelkar, Megan Swink, Jeff Radel, Joseph McGuirk, Linheng Li, George Vielhauer
Journal: Blood (2012)
Abstract 451: Pde1 Promotes Development of Pulmonary Arterial Hypertension and Could Be a Novel Treatment Target
Authors: Mai Kimura, Dai Kusumoto, Jin Komuro, Toshiomi Katsuki, Shogo Ito, Hisayuki Hashimoto, Shinsuke Yuasa, Keiichi Fukuda
Journal: Circulation Research (2019)

Backgrounds: Pulmonary arterial hypertension (PAH) is a rare but fatal disease, with an estimated mean survival period in untreated patients of approximately 3 years. Pulmonary vascular remodeling is a hallmark of PAH. Pulmonary vasculature shows increased proliferation, irrelevant migration and apoptosis resistance of vascular cells such as pulmonary arterial smooth muscle cells (PASMCs) and endothelial cells. However, the molecular mechanism in the pathogenesis of PAH remains unclear. We previously performed genome-wide association study (GWAS) in Japanese patients with idiopathic / heritable PAH and healthy controls and identified novel disease related SNPs in PDE1A
Abstract 209: iPSC Derived Cardiomyocytes Reproduce Divergent Phenotypes Caused by a LQTS Type-1 Likely Pathogenic Mutation
Authors: Antonio C Campos De Carvalho, Danubia S Santos, Tais H Brunswick, Raphaela P Ferreira, Daiana S Araujo, Bruna Farjun, Isabela C Leitão, Glauber M Dias, Jorge Coutinho, Isadora M Vaz, Tamara Brogonovo, Fernando E Cruz, Adriana B Carvalho
Journal: Circulation Research (2019)

The purpose of this work was to investigate if iPSC derived cardiomyocytes would reproduce the divergent phenotypes observed in a proband and mother that carried the same likely-pathogenic variant in KCNQ1 gene. A 15 years old proband had syncope and cardiac arrest while swimming being diagnosed with LQTS based on a 12 lead ECG. The mother’s ECG showed no abnormalities. Genomic DNA from blood of daughter and mother was extracted using standard procedures. All coding exons and flanking intronic sequences of KCNQ1 (NM_000218) genes were amplified by polymerase chain reaction. Direct sequencing was performed on a 3500XL Genetic Analyzer. Data was analyzed with Geneious software for identification of mutations. For iPSC generation CD71+ CD36+ erythroblasts were reprogrammed using CytoTune™-iPS 2.0 Sendai Reprogramming Kit on irradiated mouse embryonic fibroblast feeder layers. Differentiation into cardiomyocytes was accomplished using the protocol described by Lian et al. (2012). Electrophysiological recordings were obtained from cardiomyocytes after 30–45 days of differentiation. Cells were transferred to acrylic plates pretreated with Matrigel and kept in culture for 3 days before microelectrode action potential (AP) were registered. The ECG recordings showed a corrected QT interval (QTc) of 516 ms for the daughter and 436 ms for the mother. Sequencing showed that both daughter and mother had a c.1763C&gt;T mutation resulting in p.Ile588Thr substitution. iPSC generated from daughter, mother and an unrelated control displayed normal karyotype and expressed pluripotent genes, besides spontaneously differentiating into cells of the three germ layers. Differentiation into cardiomyocytes was ascertained by immunofluorescence and flow cytometry for troponin T. In all differentiations more than 70% of cells were cardiomyocytes. Action potentials recordings showed that ventricular cardiomyocytes from the daughter exhibited significantly longer action potential durations at 90% repolarization than the mother’s or the unrelated control’s cardiomyocytes. Cardiomyocytes derived from iPS cells reproduced the clinical phenotypes exhibited by daughter and mother.
Increasing fertility preservation counseling prior to chemotherapy.
Authors: Candice Schwartz, Ari Seifter, Ivy Abraham, Caitlin Lopes, Emily Woo, Neeta K. Venepalli, Rozina A. Chowdhery
Journal: Journal of Clinical Oncology (2019)

225 Background: The 2018 ASCO Guidelines recommend that physicians document discussions about fertility with all female patients &lt; 49 years old at the time of cancer diagnosis. Patients interested in fertility preservation (FP) should be referred to Reproductive Endocrinology and Infertility (REI) prior to chemotherapy. Retrospective review of oncology patients at our academic medical center over 6 months found that 33% of females &lt; 49 years old had FP discussion documented. We aimed to increase FP discussions and help expedite referrals to REI from 33% to 75% within 5 months. Methods: All new chemotherapy orders were reviewed weekly. Female patients between ages 18-49 were identified and charts were abstracted for the following: age, race, diagnosis, stage, type and line of chemotherapy, and FP discussion. If FP was not discussed, the physician was contacted in real time via email to address FP with the patient and document the discussion. Charts were reviewed 2-4 weeks later to determine if FP was documented. To better understand barriers to FP documentation, fellows and attendings were surveyed to target future interventions. Results: From Dec. 2018 to Apr. 2019, 6/27 (22%) patients had documented discussions of FP. Post intervention, this number increased to 17/27 (63%) with one referral to REI. Intent of chemotherapy was curative in 56% of patients, and 67% were receiving their first line of chemotherapy. 2/15 (13%) patients receiving curative treatment and 4/12 (33%) patients receiving palliative chemotherapy had documentation of FP, both of which increased with intervention to 8/15 (53%) and 9/12 (75%), respectively. Conclusions: Our intervention successfully increased FP discussion from 33% to 63%, but we did not meet our goal of 75%. Per our survey results, the most common barriers to FP discussion were time constraints, inexperience discussing FP, and perception of prohibitive cost to the patient. We are designing our next intervention to address provider inexperience with FP discussion. This will include education regarding the financial aspects of REI and discussion of the new Oncofertility law in Illinois (HB2617), which ensures insurance coverage for oncofertility as of Jan 2019.
Urinary levels of Bcl-2 are elevated in ovarian cancer
Authors: Nicole Anderson, Yira Bermudez, Donna Badgwell, Ren Chen, Santo Nicosia, Robert Bast, Patricia Kruk
Journal: Cancer Research (2008)

963  Ovarian cancer is the leading cause of gynecologic cancer death in women in the US. It is estimated that 23,000 new cases are diagnosed annually and that 14,000 women die annually from this disease. The lack of early symptoms and the absence of a reliable screening test result in over 70% of women being diagnosed after the disease has spread beyond the ovary so that the prognosis is poor (5-year survival is no better than 37%). Deregulation of apoptosis due to overexpression of anti-apoptotic proteins contributes to the malignant phenotype by supporting cancer cell growth and therapeutic resistance. Building on a previous pilot study to assess whether urinary levels of the anti-apoptotic protein Bcl-2 could be used to detect ovarian cancer, urine was collected from normal healthy volunteers (N=58), patients with benign gynecologic disease (N=122) and patients with ovarian cancer (N=115) and measured for Bcl-2 by ELISA (mean ng/ml ± S.E.). The average amount of Bcl-2 in the urine of cancer patients was > 2 ng/ml and up to 10X greater than healthy controls or patients with benign disease. Using logistic regression, the predicted odds of cancer (early or late) increased 26.9%, (p
Cases in Precision Medicine: A Personalized Approach to Stroke and Cardiovascular Risk Assessment in Women
Authors: Natalie A. Bello, Eliza C. Miller, Kirsten Lawrence Cleary, Ronald Wapner
Journal: Annals of Internal Medicine (2019)

Cardiovascular disease is the leading cause of death among women in the United States, and stroke is third. This article uses a case scenario to examine female sex-specific cardiovascular risk factors across the lifespan and describes a precision medicine-based approach to risk factor modification and primary prevention. It also presents recent updates to the role of genetic testing and polygenic risk scores for the prediction of stroke and cardiovascular disease.
Millions of people are still missing out on TB treatment, says WHO
Authors: Elisabeth Mahase
Journal: BMJ (2019)

A record seven million people around the world were treated for tuberculosis (TB) in 2018, up from 6.4 million in 2017, the World Health Organization says in its annual report on the disease.1

As 10 million new cases of TB were reported last year, however, that means three million people did not get access to the treatment they need. Deaths from TB also decreased last year, from 1.6 million in 2015 to 1.5 million people in 2018.

The figures provide an update on the progress countries are making towards the End TB strategy agreed in 2014, which challenged countries to reduce new cases by 90% and deaths from the disease by 95% between 2015 and 2035. Targets for 2020 included a 35% reduction in the number of deaths and a 20% reduction in the incidence rate.

The …
Abstract 481: Investigation into the Genetic Cause of Congenital Dilated Cardiomyopathy Using Human Induced Pluripotent Stem Cells
Authors: Kuo-chen Wang, Young Wook Chun, Charles C Hong
Journal: Circulation Research (2019)

Congenital dilated cardiomyopathy (cDCM) is a rare but typically fatal disease. In most cases, its etiology is unknown, but a genetic root cause is often suspected. The objective of current study is to determine whether a novel non-structural gene causes cDCM. We hypothesized that rare genetic mutations caused cDCM, which could be modeled using patient-derived induced pluripotent stem cells (iPSCs). We generated the cardiomyocytes from iPSCs of a cDCM proband and found significant impairment in contractility and mitochondrial function, compared to those of healthy controls. To identify the causal mutations, we performed a whole exome sequencing of the cDCM patient and his parents (“trio”). Based on the assumption of recessive mode of inheritance or a de novo mutation, 9 candidate causal genes were identified. On the ground of the expression profiles of trio and pathogenicity predictor algorithms, we identified an indel and a nonsynonymous point mutation in the rotatin (encoded by RTTN ) gene as the putative genetic defect responsible for cDCM. CRISPR/Cas9-mediated knockout of RTTN in healthy control iPSCs recapitulated cardiomyocyte defects, and the correction of the missense mutation in the disease iPSCs restored cardiomyocyte structure and function, confirming causality. Thus, rotatin is a new causal molecule for cDCM and plays an important role in cardiac regulation.
A Rare Form of Lipid Metabolic Encephalopathy
Authors: Qian Qian, Du Cao, You-Dong Wei
Journal: JAMA Neurology (2019)

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The Epigenetic Regulator Ezh2 Is An Effective Target For Controlling Th1 Cell-Mediated Acquired Aplastic Anemia In Mice
Authors: Qing Tong, Shan He, Fang Xie, Amanda Wong, Kazuhiro Mochizuki, Yongnian Liu, Izumi Mochizuki, Shin Mineishi, Yi Zhang
Journal: Blood (2013)
Therapy With Demethylating Agents Significantly Improves Overall- and AML-Free Survival In Patients With MDS Classified As High-Risk By IPSS Or Very High Risk By IPSS-R and Partial Or Total Monosomy 7-Results From a German Multicenter Study
Authors: Julie Schanz, Friederike Braulke, Katayoon Shirneshan, Kathrin Nachtkamp, Ulrich Germing, Stephan Schmitz, Peter Haas, Michael Lübbert, Catharina Müller-Thomas, Katharina Götze, Uwe Platzbecker, Florian Nolte, Wolf-Karsten Hofmann, Detlef Haase
Journal: Blood (2013)