tbuckley/cabot-search huggingface dataset:
The origin of GPI-AP deficient cells in MDS, MPD, and aplastic anemia and its significance in predicting leukemic transformation.
Authors: Jeffrey J. Pu, Jerry L. Spivak, Robert A. Brodsky, Alison Moliterno
Journal: Journal of Clinical Oncology (2013)

7032 Background: PNH is a clonal disorder originating from a multipotent hematopoietic stem cell (HSC) acquiring a PIG-A gene mutation. PIG-A mutation lead to glycosylphosphatidylinositol-anchor protein (GPI-AP) deficiency, which contributes to many manifestations of PNH. About 25% of MDS and MPD, and 60% of AA also harbor small population of PNH-like cells. It was observed that 1) 10-20% AA harboring PNH-like cells eventually transform into PNH; but MDS and MPD seldom evolve to PNH; 2) AA harboring PNH-like cells may have a better response to immunosuppressive therapy; and 3) PIG-A mutation frequency significantly increased in some human cell lines with genomic instability. However, the clinical significances of these PNH-like cells in MDS, MPD, and AA are unclear. Methods: We prospectively recruit MDS, MPD, and AA patients. Peripheral blood flow cytometry is used to identify GPI-AP deficient blood cells, a proaerolysin-resistant CFC assay is used to select GPI-AP deficient progenitor cells, a novel T cell enrichment assay with proaerolysin selection is used to expand GPI-AP deficient T cells, and RT-PCR assay and DNA sequencing assay are used to identify and analyze particular gene expression deficiency in GPI-AP biosynthesis. Results: Our preliminary data shows that PNH-like cells in AA arise from multipotent HSC harboring PIG-A mutation; in MDS initiated at progenitor harboring PIG-A mutations and are transient; and in MPD caused from PIG-Y gene transcriptional silencing. Interestingly, the PIG-A mutation frequency in 4 MDS harboring PNH-like cells were 10~100 times higher than healthy controls. Furthermore, these 4 MDS and 3 MPD harboring PNH-like cells rapidly transformed into acute myelogenous leukemia. Conclusions: The origins and the clonality of PNH-like cells are different among MPD, MDS, and AA. This may explain why AA often evolves into PNH, but MPD and MDS seldom transform into PNH. PNH-like cell population in MPD and MDS is a marker of genomic instability and may predict a risk of leukemic transformation.
Clinical outcome of taxane-resistant (TR) hormone refractory prostate cancer (HRPC) patients (pts) treated with subsequent chemotherapy (ixabepilone (Ix) or mitoxantrone/prednisone (MP)
Authors: A. M. Lin, J. E. Rosenberg, V. K. Weinberg, W. K. Kelly, M. D. Michaelson, M. Hussain, G. Wilding, M. E. Gross, E. J. Small
Journal: Journal of Clinical Oncology (2006)

4558 Background: The clinical course of TR HRPC pts has not previously been evaluated in a large, prospective study. No standard treatment exists for this pt population, although MP is frequently used. Ix is an epothilone B analogue with activity against TR cell lines. Methods: Metastatic HRPC pts with disease progression during or within 60 days of stopping T chemotherapy were eligible. In a 2-arm, non-comparative randomized phase II study, pts were assigned to receive either: 1) M 14 mg/m 2 IV q3wks and P 5 mg PO BID or 2) I × 35 mg/m 2 IV q3wks. Crossover was allowed for progression or toxicity. The study’s primary endpoint was to detect a ≥ 50% PSA decline by Consensus Criteria in at least 25% of 2 nd -line pts (H 0 = 10%, α = 0.04, β = 0.18 for each arm). Pts were followed for survival. Results: Forty-one evaluable pts each were accrued to Ix and to MP. The median follow-up is 5.0 months (range: 0.3–19.5). The median number of cycles administered to each 2 nd -line arm is 3 (range: Ix: 1–8, MP: 1–12). Median survival from protocol entry is 13.0 months with Ix and 12.5 months with MP. Confirmed 2 nd -line post-therapy (rx) ≥50% PSA declines were observed in 17% of Ix pts (95% CI = 7–32) and 20% of MP pts (95% CI = 9–35). Of pts with measurable disease, partial responses were observed in 1/18 pts on 2 nd -line Ix (6%; 95% CI = 0.1–27.3) and in 1/15 pts on 2 nd -line MP (7%; 95% CI = 0.2–31.9). Median duration on 2 nd -line Ix and MP was 2.2 months and 2.3 months, respectively. Crossover to 3 rd -line rx occurred in 39% of Ix pts and 68% of MP pts. Confirmed 3 rd -line post-rx ≥50% PSA declines were observed in 3/24 Ix pts and in 4/13 MP pts. The most common grade 3/4 toxicity associated with 2 nd -line rx was neutropenia as previously reported (41% of Ix pts, 54% of MP pts). Conclusions: This prospective trial has characterized TR HRPC pts as having an observed median survival of approximately 1 year. This may be a useful reference for the screening of effective agents in the 2 nd -line setting for TR HRPC. Both Ix and MP appear to have only modest activity as 2 nd - and 3 rd -line rx in this highly selected TR HRPC population. This study was supported by Bristol-Myers Squibb and the Prostate Cancer Foundation. No significant financial relationships to disclose.
RELATIONSHIP BETWEEN LOW-DENSITY LIPOPROTEIN CHOLESTEROL, LIPID LOWERING AGENTS AND THE RISK OF STROKE: A META-ANALYSIS OF OBSERVATIONAL STUDIES AND RANDOMIZED CONTROLLED TRIALS
Authors: Maciej Banach, Niloofar Shekoohi, Dimitri Mikhailidis, Gregory Lip, Adrian V. Hernandez, Mohsen Mazidi
Journal: Journal of the American College of Cardiology (2020)
Causal relationships between NAFLD, T2D and obesity have implications for disease subphenotyping
Authors: Zhipeng Liu, Yang Zhang, Sarah Graham, Xiaokun Wang, Defeng Cai, Menghao Huang, Roger Pique-Regi, Xiaocheng Charlie Dong, Y. Eugene Chen, Cristen Willer, Wanqing Liu
Journal: Journal of Hepatology (2020)
Expression of vascular endothelial growth factor receptor (VEGF-R) and CD31 receptor (CD31-R) in high-grade neuroendocrine carcinoma of the uterine cervix (cNEC) and its association with prognosis.
Authors: James A Kuzman, Boris G. Naraev, Anna M Button, Megan I Samuelson, Michael J Goodheart, Barry DeYoung, Thomas M. O'Dorisio, Thorvardur Ragnar Halfdanarson
Journal: Journal of Clinical Oncology (2012)

e15580 Background: High-grade cNEC is uncommon cancer, and the optimal treatment is unclear. It is not known if cNEC expresses surface proteins related to angiogenesis. The aim of this study is to evaluate the expression of proteins involved in angiogenesis, as well as their possible association with clinical outcomes. Methods: Expression of VEGF-R and CD31-R was analyzed with standard immunohistochemical methods in tumor specimens from 16 patients with cNEC seen at our institution from 1977 to 2010. CD31-R expression was estimated by analyzing microvessel density using a CD31 specific antibody. Intensity and percentage of cells expressing VEGF-R was determined. Univariate survival analysis was performed using a Cox Proportional Hazard Model. Results: VEGF-R was expressed in 15 out of 16 specimens whereas CD31-R was expressed in all specimens. Increased VEGF-R expression correlated with shortened survival but the association was not statistically significant (p=0.0544, hazard ratio=1.514, CI=0.992-2.309). A one unit increase in VEGF-R expression correlated with increase in the risk of death by 51.4%. CD31-R expression showed no significant association with survival (p=0.9638,CI=0.865-1.165). Conclusions: VEGF-R and CD31-R are expressed by most cNECs. Increased VEGF-R, but not CD31-R, expression may be associated with worse survival. Further exploration of the role of angiogenesis in cervical NETs is warranted.
ASSESSMENT OF NUTRITION STATUS IS ESSENTIAL TO PREDICT PROGNOSIS OF ACUTE MYOCARDIAL INFARCTION PATIENTS WHO UNDERGO SUCCESSFUL PRIMARY PERCUTANEOUS CORONARY INTERVENTION
Authors: Daisuke Kanda, Yoshiyuki Ikeda, Kazuhiro Anzaki, Ryou Arikawa, Takeshi Sonoda, Akihiro Tokushige, Mitsuru Ohishi
Journal: Journal of the American College of Cardiology (2020)
MANAGEMENT OF A FISTULA BETWEEN THE LEFT CIRCUMFLEX CORONARY ARTERY AND CORONARY SINUS IN UNSTABLE ANGINA
Authors: Piotr J. Horbal, Ihab Hassanieh, Ghassan Daher, Zachary Oman, Eldin Duderija, Deana Mikhalkova
Journal: Journal of the American College of Cardiology (2020)
THE UNFAVORABLE RELATION OF VENTRICULAR CONDUCTION DELAY, DYSFUNCTION AND REMODELING IN ISOLATED LEFT BUNDLE-BRANCH BLOCK
Authors: Janek Salatzki, Theresa Fischer, Johannes Riffel, Florian André, Kristóf Hirschberg, Hauke Hund, Evangelos Giannitsis, Eberhard Scholz, Matthias Gero Friedrich, Hugo Katus, Marco Ochs
Journal: Journal of the American College of Cardiology (2020)
PROGNOSTIC VALUE OF IMPORTANT PERIPROCEDURAL TIME INTERVALS IN PATIENTS WITH ANTERIOR ST ELEVATION MYOCARDIAL INFARCTION AFTER SUCCESSFUL REPERFUSION BY PRIMARY PERCUTANEOUS INTERVENTION AS DETECTED BY CARDIAC MAGNETIC RESONANCE IMAGING
Authors: Diaa Kamal, Mostafa Ibrahim, Ahmed S. Ibrahim, R. Raymond
Journal: Journal of the American College of Cardiology (2020)
THE IMPACT OF THE REVISED UNITED NETWORK OF ORGAN SHARING (UNOS) HEART ALLOCATION POLICY ON TRANSPLANT WAITLIST TIMES AND POST TRANSPLANT MORTALITY
Authors: Jonathan Nattiv, Grace Liu, Pooya Banankhah, Joseph Rahman, Kruti Pandya, Aaron M. Wolfson, Eugene Christopher DePasquale, Ajay Vaidya
Journal: Journal of the American College of Cardiology (2020)
RNA G-quadruplex regulates microRNA-26a biogenesis and function
Authors: Geng Liu, Wenya Du, Haixia Xu, Qiu Sun, Dongmei Tang, Sailan Zou, Yu Zhang, Meilin Ma, Guixiang Zhang, Xiao Du, Shenggen Ju, Wei Cheng, Yan Tian, Xianghui Fu
Journal: Journal of Hepatology (2020)
ADVERSE PREGNANCY OUTCOMES AND MID-LIFE CARDIAC MECHANICS: THE CORONARY ARTERY RISK DEVELOPMENT IN YOUNG ADULTS STUDY
Authors: Priya P. Mehta, Laura Colangelo, Abbi Lane-Cordova, Amanda M. Perak, Philip Greenland, William Grobman, Sanjiv Shah, Mercedes Carnethon, Janet Catov, Norrina Allen, Erica P. Gunderson, Sadiya Khan
Journal: Journal of the American College of Cardiology (2020)
Quality of life assessment in patients above 60, below 50 years of age during and after curative radiotherapy in head and neck cancers
Authors: A. Turaka, B. K. Mohanti, S. Chander, S. V. Deo, R. Jena, G. K. Rath
Journal: Journal of Clinical Oncology (2006)

5552 Background: To evaluate the Quality of life in patients above 60 and below 50 years during and after curative radiotherapy in head and neck cancers. Methods: Head and Neck cancer patients who are to undergo curative radiotherapy (RT) were divided into two groups, 49 patients (Group A,above 60 years) and 40 patients (Group B,below 50). Quality of life assessment was done using EORTC QLQ C-30 version-2 at 4 phases;Pretreatment-Phase I,during RT-Phase II,1-month post RT-Phase III and 6 months post RT-Phase IV.Statistical analysis was done with mean scores using ’t’ test. Results: Physical functioning (PF)scores in both groups were highest in phase I (69.4;77.5, p &lt; 0.035) and lowest in phase II (40; 50, p &lt; 0.008) and the difference was statistically significant. Although PF scores declined in both groups in phase II, overall PF score remained higher in group B than in group A in all phases.Role functioning score remained low in both groups and the difference were not statistically significant at all phases. Emotional functioning score was highest in phase I (68.37; 69.15), but declined as treatment progressed, consequent to depression.The values improved over time, restored to near pretreatment values at phase IV. Cognitive functioning scores in both groups was also highest in phase I (70.07; 79.17). Social functioning of both groups declined during RT (42.52; 45)compared to pre RT values (73.47; 77.09). The mean Global Health Status score was higher in group B compared to group A at all phases, yet there was no statistical significance.The scores declined during RT (66.87 vs 35.62 &amp; 64.79 vs 34.01), improved overtime but did not reach pre RT scores.The symptom scores were all higher for elderly patients compared with younger patients at all phases, implying elderly patients experienced more symptoms, with greater experience of symptoms during RT. Conclusions: Quality of Life of elderly patients was lower compared to younger patients at phase II in terms of physical functioning, social and emotional functioning. Global Health Status score was higher for younger patients than elderly at all phases, and declined in phase II. No significant financial relationships to disclose.
Abstract 19348: RING Finger Protein 207 (RNF207) Degrades T613M Human Ether-a-Go-Go Related Gene (hERG) Mutant
Authors: Hannah A Ledford, Seojin Park, Padmini Sirish, Wilson Xu, Valeriy Timofeyev, Xiao-Dong Zhang, James R Priest, Marco V Perez, Vladimir Yarov-Yarovoy, Nipavan Chiamvimonvat
Journal: Circulation (2017)

Introduction: Human ether-a-go-go related gene (hERG) channel underlies cardiac rapidly activating delayed rectifier K+ current (IKr); hERG mutations contribute to Long QT Syndrome (LQTS) Type 2. I...
HSR20-085: Real-World Study of Factors Associated With Breast Conserving Surgery for Females Diagnosed With Early Stage Breast Cancer
Authors: Judy George, Joseph Tkacz, M. Christopher Roebuck, Fredy Reyes, Yull E. Arriaga, Gretchen P. Jackson, Irene Dankwa-Mullan
Journal: Journal of the National Comprehensive Cancer Network (2020)

"HSR20-085: Real-World Study of Factors Associated With Breast Conserving Surgery for Females Diagnosed With Early Stage Breast Cancer" published on 20 Mar 2020 by National Comprehensive Cancer Network.
APPLYING REWIND CVD CRITERIA TO SUSTAIN 6 AND PIONEER 6: AN EXPLORATORY ANALYSIS OF CV OUTCOMES WITH SEMAGLUTIDE
Authors: Subodh Verma, Udi Fainberg, Mansoor Husain, Søren Rasmussen, Lars E. Ryden, Maria Sejersten Ripa, John B. Buse
Journal: Journal of the American College of Cardiology (2020)
Dynamic Evolution of Euchromatic Satellites on the X Chromosome in Drosophila melanogaster and the simulans Clade
Authors: John S Sproul, Danielle E Khost, Danna G Eickbush, Sherif Negm, Xiaolu Wei, Isaac Wong, Amanda M Larracuente
Journal: Molecular Biology and Evolution (2020)

Abstract Satellite DNAs (satDNAs) are among the most dynamically evolving components of eukaryotic genomes and play important roles in genome regulation, genome evolution, and speciation. Despite their abundance and functional impact, we know little about the evolutionary dynamics and molecular mechanisms that shape satDNA distributions in genomes. Here, we use high-quality genome assemblies to study the evolutionary dynamics of two complex satDNAs, Rsp-like and 1.688 g/cm3, in Drosophila melanogaster and its three nearest relatives in the simulans clade. We show that large blocks of these repeats are highly dynamic in the heterochromatin, where their genomic location varies across species. We discovered that small blocks of satDNA that are abundant in X chromosome euchromatin are similarly dynamic, with repeats changing in abundance, location, and composition among species. We detail the proliferation of a rare satellite (Rsp-like) across the X chromosome in D. simulans and D. mauritiana. Rsp-like spread by inserting into existing clusters of the older, more abundant 1.688 satellite, in events likely facilitated by microhomology-mediated repair pathways. We show that Rsp-like is abundant on extrachromosomal circular DNA in D. simulans, which may have contributed to its dynamic evolution. Intralocus satDNA expansions via unequal exchange and the movement of higher order repeats also contribute to the fluidity of the repeat landscape. We find evidence that euchromatic satDNA repeats experience cycles of proliferation and diversification somewhat analogous to bursts of transposable element proliferation. Our study lays a foundation for mechanistic studies of satDNA proliferation and the functional and evolutionary consequences of satDNA movement.
Abstract 15896: Computational Mathematical Analysis of Different Stent Geometries and Arterial Wall Response in Tortuous Coronary Artery
Authors: Suncica Canic, Yifan Wang, David Esteban Paniagua, Jonanlis Ramirez, Lizy Paniagua, Raymundo Quintana Quezada, Hani Jneid, Ali E Denktas, David Paniagua
Journal: Circulation (2019)

Background: The biological response of a coronary artery can be assessed measuring the radial stress of the arterial wall, which depend on the location, arterial tortuosity, and cardiac cycle. We s...
ASSOCIATIONS OF INDIVIDUAL PLASMA NON-ESTERIFIED FATTY ACIDS WITH INCIDENT ATRIAL FIBRILLATION IN OLDER ADULTS: THE CARDIOVASCULAR HEALTH STUDY
Authors: Cara Pellegrini, Jorge Kizer, Petra Buzkova, Nirupa Matthan, Alice Lichtenstein, David Siscovick, Joachim Ix, Susan R. Heckbert, Kenneth Mukamal, Luc Djousse
Journal: Journal of the American College of Cardiology (2020)
LIMITED TESTING FOR CORONARY ARTERY DISEASE IN PATIENTS WITH NEW-ONSET HEART FAILURE: FINDINGS FROM GET WITH THE GUIDELINES - HEART FAILURE
Authors: Kyle O'Connor, Todd Brophy, Gregg C. Fonarow, Ron Blankstein, Rajesh V. Swaminathan, Haolin Xu, Roland Matsouaka, Nancy M. Albert, Eric J. Velazquez, Clyde W. Yancy, Paul A. Heidenreich, Adrian Hernandez, Adam DeVore
Journal: Journal of the American College of Cardiology (2020)
Effectiveness and Safety of Apixaban Compared With Rivaroxaban for Patients With Atrial Fibrillation in Routine Practice
Authors: Michael Fralick, Michael Colacci, Sebastian Schneeweiss, Krista F. Huybrechts, Kueiyu Joshua Lin, Joshua J. Gagne
Journal: Annals of Internal Medicine (2020)

Apixaban and rivaroxaban are the most commonly prescribed direct oral anticoagulants for adults with atrial fibrillation, but head-to-head data comparing their safety and effectiveness are lacking.
TORTUOUS CORONARY SEGMENTS WITH BENDING AND STRETCHING MOTION: A POSSIBLE PREVENTIVE FACTOR AGAINST CORONARY ATHEROSCLEROSIS
Authors: Kazuto Kurihara, Yoshiharu Fujimori, Yasushi Yamanaka, Tomoko Baba, Satoshi Hashimoto, Wataru Takeuchi, Tadamasa Wakabayashi, Daisuke Yokota, Taku Imai
Journal: Journal of the American College of Cardiology (2020)
WhatsGNU: a tool for identifying proteomic novelty
Authors: Ahmed M. Moustafa, Paul J. Planet
Journal: Genome biology (2020)

Abstract To understand diversity in enormous collections of genome sequences, we need computationally scalable tools that can quickly contextualize individual genomes based on their similarities and identify features of each genome that make them unique. We present WhatsGNU, a tool based on exact match proteomic compression that, in seconds, classifies any new genome and provides a detailed report of protein alleles that may have novel functional differences. We use this technique to characterize the total allelic diversity (panallelome) of Salmonella enterica , Mycobacterium tuberculosis , Pseudomonas aeruginosa, and Staphylococcus aureus . It could be extended to others. WhatsGNU is available from https://github.com/ahmedmagds/WhatsGNU .
Generalizability of Clinical Trials Supporting the 2017 American College of Cardiology/American Heart Association Blood Pressure Guideline
Authors: Timothy S. Anderson, Michelle Odden, Joanne Penko, Dhruv S. Kazi, Brandon K. Bellows, Kirsten Bibbins-Domingo
Journal: JAMA Internal Medicine (2020)

This study uses National Health and Nutrition Examination Survey data to evaluate whether patients enrolled in the clinical trials that support the American College of Cardiology/American Heart Association (ACC/AHA) guideline are representative of the US adult population recommended additional pharmacotherapy by the ACC/AHA guideline.
A Computational Approach for Modeling the Allele Frequency Spectrum of Populations with Arbitrarily Varying Size
Authors: Hua Chen
Journal: Genomics Proteomics & Bioinformatics (2019)

Abstract The allele frequency spectrum (AFS), or site frequency spectrum, is commonly used to summarize the genomic polymorphism pattern of a sample, which is informative for inferring population history and detecting natural selection. In 2013, Chen and Chen developed a method for analytically deriving the AFS for populations with temporally varying size through the coalescence time-scaling function. However, their approach is only applicable to population history scenarios in which the analytical form of the time-scaling function is tractable. In this paper, we propose a computational approach to extend the method to populations with arbitrary complex varying size by numerically approximating the time-scaling function. We demonstrate the performance of the approach by constructing the AFS for two population history scenarios: the logistic growth model and the Gompertz growth model, for which the AFS are unavailable with existing approaches. Software for implementing the algorithm can be downloaded at http://chenlab.big.ac.cn/software/.
Outcomes and clinical markers associated with benefit from ipilimumab (Ipi) in patients with advanced melanoma: A retrospective single-institution study.
Authors: Zachary Franklin Zimmerman, Barry Storer, Amandeep Godara, John A. Thompson, Kim Allyson Margolin, Scott S. Tykodi, Jason K. Rockhill, Sylvia Mina Lee, Anna Brown, Amila Patel, Jon Smith, Shailender Bhatia
Journal: Journal of Clinical Oncology (2013)

e20048 Background: Ipi (anti-CTLA4 antibody) is associated with improved survival and durable responses in a subset of melanoma pts. However, the optimal dose and schedule remain unclear and an unmet need to identify predictors of clinical benefit exists. This retrospective study of pts at the University of Washington aims at gaining further insight into these questions. Methods: Efficacy and safety outcomes and baseline characteristics of 126 pts receiving single agent Ipi from 2006-2012 were subjected to univariate analysis. Efficacy endpoints included OS, PFS, ORR and Duration of Clinical Benefit (DCB) defined as the time from Ipi initiation until documented progression or change in therapy (to capture outcomes on non-trial pts). Immune-related adverse events (IRAEs), absolute lymphocyte count (ALC), concordance of disease response by metastatic site, and use of radiation therapy (RT) were also analyzed. Results: The median age was 57.7 yrs. The 3 mg/kg (N=84; 67%) and 10 mg/kg (N=42; 33%) cohorts matched well for standard prognostic criteria. The efficacy endpoints, including OS, PFS, DCB, and ORR (see table) were not significantly different for the 3 mg/kg and 10 mg/kg cohorts. However, grade III/IV IRAEs were more frequent in the 10 mg/kg group (33% vs 17%, p=0.04). There was a significant correlation between efficacy outcomes and development of IRAEs (see table). Baseline ALC or changes in ALC at 7 weeks post-therapy and concurrent RT administration did not significantly correlate with improved outcomes. Responses were concordant between CNS and non-CNS sites. Conclusions: Our data supports the currently approved dose of 3mg/kg. The development of IRAEs was significantly associated with clinical benefit and further confirmation of this association is warranted. Results of other exploratory analyses will be presented at the meeting. [Table: see text]
CLO20-033: A Study of Pathological Characteristics of Malignant Cribriform Prostatic Lesions
Authors: Thi Thanh Tam Bui, Quoc Thang Pham, Dang Anh Thu Phan, Quoc Dat Ngo, Thanh Hai Phan, Thi Ngoc Ha Hua, Sao Trung Nguyen
Journal: Journal of the National Comprehensive Cancer Network (2020)