tbuckley/cabot-search huggingface dataset:
A RETROSPECTIVE REVIEW OF HOW THE NEW UNOS HEART TRANSPLANT DONOR ALLOCATION POLICY AFFECTED URGENT STATUS LISTING AND OUTCOMES IN STATUS 1, 2, AND 3 LISTING COMPARED TO THE OLD STATUS 1A
Authors: Danny Ramzy, Robert Cole, Michelle Kittleson, Ryan Levine, Dominic Emerson, Dominick Megna, Fardad Esmailian, Jaime Moriguchi, Jon A. Kobashigawa
Journal: Journal of the American College of Cardiology (2020)
Identification of ephrinB2 positive vessels in non-Hodgkin lymphoma subtypes.
Authors: Kenneth Stuart Cohen, Mina Jamali, Elizabeth Hyjek
Journal: Journal of Clinical Oncology (2013)

e19542 Background: Current anti-angiogenic therapies for tumors target signaling pathways such as VEGF. However, the role of alternative vascular pathways in tumor biology in general, and lymphoma biology specifically, are less well understood. Recently, the Eph receptor tyrosine kinase signaling pathway has emerged as a novel target for therapeutic inhibition. The EphB family member EphB4, and its reverse signaling ligand ephrinB2, are indispensible for developmental angiogenesis. Inhibition of ephrinB2 signaling results in impaired tumor growth in pre-clinical models. We therefore sought to determine if ephrinB2 is expressed in the microenvironment of human lymphomas and thereby represents a novel therapeutic target. Methods: We evaluated by immunohistochemistry on paraffin tissue sections expression of ephrinB2, CD34 (endothelial cells) and CD163 (macrophages) in LN biopsies from 12 cases of FL and 11 cases of DLBCL retrieved from the archives of the Department of Pathology at the University of Chicago (2000-2011). Eleven cases of follicular hyperplasia or quiescent LNs were used as controls (Cs). Slides were digitally scanned and examined both semi-quantitatively and by digital image analysis. Stained cells were quantified both in internal areas and at lymphoma-fat interfaces. Results: CD34+ microvessel densities were comparable between DLBCL and C groups but showed a significantly higher trend of interface angiogenic sprouts in FLs. Interface recruited CD163+ cell numbers were significantly higher in DLBCLs than in both FLs and Cs (p&lt;0.0001). EphrinB2-expressing blood vessels were significantly increased in FLs but not in DLBCL. Conclusions: FLs demonstrate an increase in ephrinB2+/CD34+ vessels at the lymphoma-fat interface. In contrast, DLBCLs demonstrate no increase in ephrinB2+ vessels versus controls. However, DLBCLs were notable for increased recruitment of CD163+ macrophages at the tumor/host interface. These data represent the first analysis of ephrinB2 expression in human lymphomas and demonstrate heterogeneity between locations within a lymphoma and between histologic subtypes. Analysis of ephrinB2 in human lymphomas reveals marked heterogeneity in lymphoma microenvironmental domains.
Clinical pharmacokinetics (PK) of AMN107, a novel inhibitor of Bcr-Abl, in healthy subjects and patients with imatinib resistant or intolerant chronic myelogenous leukemia (CML) or relapsed/refractory Ph+ acute lymphocytic leukemia (Ph+ALL)
Authors: C. Tanaka, T. Smith, H. Kantarjian, F. Giles, O. Ottmann, K. Bhalla, K. Grouss, V. Sethuraman, K. Thomas, H. Schran
Journal: Journal of Clinical Oncology (2006)

3095 Background: AMN107, a selective and potent inhibitor of Bcr-Abl tyrosine kinase, has demonstrated activity against imatinib resistant forms of Bcr-Abl in patients with CML or Ph+ALL in a phase I study. This study characterizes clinical PK of AMN107 for the safe and effective use of the drug. Methods: Serum samples were collected in 119 patients with CML or Ph+ALL treated with once (QD) or twice daily (BID) oral AMN107 (doses of 50 to 1200 mg/day). PK parameters were derived from serum concentration-time data by non-compartmental methods. In separate multi-period crossover studies 92 healthy subjects were treated with single doses of AMN107 to assess the food effect on PK, and to assess the potential for drug-drug interactions with medications which inhibit (ketoconazole) or are metabolized by CYP3A4 (midazolam). Results: Steady-state AMN107 PK in patients were stable over time, and showed a dose-dependency with less than dose-proportional increases in systemic exposure at dose levels higher than 400 mg QD. Daily exposure at 400 mg BID, which maintains serum AMN107 levels at least 30 times higher than the IC 50 of cellular phosphorylation of Bcr-Abl, was greater than at 800 mg QD. The effective half-life was 15 hours. Bioavailability of AMN107 administered with a high-fat meal was increased by 82% compared to fasting. CYP3A4 inhibition by concomitantly administered ketoconazole produced 3-fold increases in systemic exposure to AMN107, whereas AMN107 appeared a weak inhibitor of CYP3A4 with 30% increase in systemic exposure of midazolam given concomitantly. Conclusions: Systemic AMN107 levels at an oral AMN107 dose of 400 mg BID in patients with CML or Ph+ALL were well above the IC 50 of Bcr-Abl. The food/drug interaction results provide further guidance for the safe use of AMN107 in the clinical setting. [Table: see text]
Patient-reported outcomes and quality of life in recessive dystrophic epidermolysis bullosa: A global cross-sectional survey
Authors: Victor A. Eng, Daniel C. Solis, Emily S. Gorell, Sara Choi, Jaron Nazaroff, Shufeng Li, Mark P. de Souza, Dedee F. Murrell, M. Peter Marinkovich, Jean Y. Tang
Journal: Journal of the American Academy of Dermatology (2020)
VISIT-TO-VISIT VARIABILITY OF LOW-DENSITY LIPOPROTEIN CHOLESTEROL MAY ASSOCIATE WITH PLAQUE RUPTURE LEADING TO ACUTE CORONARY SYNDROME
Authors: Shinsuke Nakano, Hiromasa Otake, Hiroyuki Kawamori, Takayoshi Toba, Akira Nagasawa, Onishi Hiroyuki, Ryo Takeshige, Yoichiro Sugizaki, Yoichiro Matsuoka, Kosuke Tanimura, Yu Takahashi, Yusuke Fukuyama, Shunsuke Kakizaki, Daichi Fujimoto, Koichi Nakamura, Ken-ichi Hirata
Journal: Journal of the American College of Cardiology (2020)
IMPACT OF PRE-PROCEDURAL PULMONARY ARTERIAL HYPERTENSION AND MITRAL REGURGITATION ON LONG TERM MORTALITY IN PATIENTS WITH LEFT VENTRICULAR ASSIST DEVICES
Authors: Harveen Lamba, Riyad Kherallah, Ajith Nair, Leo Simpson, Raymond Stainback, Joggy George, Gabriel Loor, Alexis Shafii, Kenneth Liao, O.H. Frazier, Andrew B. Civitello, Srikanth Koneru
Journal: Journal of the American College of Cardiology (2020)
LENGTH OF MEMBRANOUS SEPTUM POST IMPLANT PREDICTS RISK FOR PERMANENT PACEMAKER PLACEMENT AND PACING REQUIREMENTS AFTER TRANS-CATHETER AORTIC VALVE REPLACEMENT
Authors: Adnan Kassier, Jennifer Schuitema, Maliha Berner, Nabin ManandharShrestha, Stefan Jovinge, Andre Gauri, Jamie Frost, William Merhi, Nagib Chalfoun
Journal: Journal of the American College of Cardiology (2020)
COMPARISON OF OUTCOMES IN TRANSPLANT PATIENTS UNDERGOING TRANSCATHETER VERSUS SURGICAL AORTIC VALVE REPLACEMENT
Authors: Yasser Sammour, Yasser Al-Khadra, Lars G. Svensson, Faisal Bakaeen, Grant W. Reed, Rishi Puri, Murat Tuzcu, James Yun, Amar Krishnaswamy, Samir Kapadia
Journal: Journal of the American College of Cardiology (2020)
Prognostic significance of clinical features and Akt activation in the survival of patients with bronchioloalveolar carcinoma (BAC)
Authors: M. S. Ballas, J. Tsurutani, S. Steinberg, M. Robertson, V. Egilsson, P. A. Dennis
Journal: Journal of Clinical Oncology (2006)

7217 Background: Lung cancer is the leading cause of cancer related mortality in the world. BAC is a subset of NSCLC that has recently gained attention because of enhanced efficacy of epidermal growth factor receptor (EGFR) inhibitors in this population. Prognostic features for BAC have not been well defined. Because activation of Akt is a poor prognostic factor for other types of NSCLC, and because changes in Akt may predict outcome for EGFR inhibitors, we assessed the prognostic significance of clinical features and Akt activation in patients with BAC. Methods: 46 cases of BAC were classified according to WHO 2001 criteria. Akt activation was assessed using immunohistochemistry. Associations between ordered Akt levels and other dichotomous parameters were evaluated using an exact Cochran-Armitage test for trend. Survival was analyzed by the Kaplan-Meier method, and hazard ratios (HR) were determined based on Cox proportional hazard models. Results: Tissues from 45 patients were analyzed. Age and histology (mucinous vs. non-mucinous) were not associated with survival. Akt activation was observed in 63% of cases, but was not associated with differences in survival. Complete clinical data (except smoking) were available for 43 patients, and smoking history was available for 31 patients (8 never-smokers, 23 smokers). Cox model analysis revealed that male gender (HR 2.24, 95% CI 1.07–4.71, p = 0.032) and advanced stage (III or IV) (HR 2.17, 95% CI 1.004–4.71, p = 0.049) were associated with a worse prognosis. A model limited only to the 31 patients with smoking data demonstrated that smoking alone (HR 6.89, 95% CI 1.49–31.88, p = 0.013) was associated with a worse prognosis. Conclusions: These studies identify gender, stage, and especially smoking status as potentially important prognostic features for BAC. Akt was not prognostic. Given that the recent NSCLC clinical trials with erlotinib and gefitinib that showed varying survival benefit did not stratify by smoking status and BAC, it is possible that these characteristics could have affected the clinical outcomes. Investigators studying EGFR inhibitors should consider stratifying by smoking status and BAC to determine if there are subsets of patients who could benefit most from these therapies. No significant financial relationships to disclose.
Relative Model Fit Does Not Predict Topological Accuracy in Single-Gene Protein Phylogenetics
Authors: Stephanie J Spielman
Journal: Molecular Biology and Evolution (2020)

It is regarded as best practice in phylogenetic reconstruction to perform relative model selection to determine an appropriate evolutionary model for the data. This procedure ranks a set of candidate models according to their goodness of fit to the data, commonly using an information theoretic criterion. Users then specify the best-ranking model for inference. Although it is often assumed that better-fitting models translate to increase accuracy, recent studies have shown that the specific model employed may not substantially affect inferences. We examine whether there is a systematic relationship between relative model fit and topological inference accuracy in protein phylogenetics, using simulations and real sequences. Simulations employed site-heterogeneous mechanistic codon models that are distinct from protein-level phylogenetic inference models, allowing us to investigate how protein models performs when they are misspecified to the data, as will be the case for any real sequence analysis. We broadly find that phylogenies inferred across models with vastly different fits to the data produce highly consistent topologies. We additionally find that all models infer similar proportions of false-positive splits, raising the possibility that all available models of protein evolution are similarly misspecified. Moreover, we find that the parameter-rich GTR (general time reversible) model, whose amino acid exchangeabilities are free parameters, performs similarly to models with fixed exchangeabilities, although the inference precision associated with GTR models was not examined. We conclude that, although relative model selection may not hinder phylogenetic analysis on protein data, it may not offer specific predictable improvements and is not a reliable proxy for accuracy.
Induction chemotherapy with docetaxel plus carboplatin followed by concomitant chemoradiotherapy (CRT) in locally advanced non-small cell lung cancer (NSCLC).
Authors: Inas Ibraheim Abdel Halim, Wael El-Sadda, Mohamed El Ashry, Nehal Mohammed Elmashad
Journal: Journal of Clinical Oncology (2013)

e18505 Background: Lung cancer remains the leading cause of cancer death in both men and women. One third of patients with NSCLC presents with localized unresectable disease. With the adavance in the diagnostic and therapeutic procedures, the median survival has shown substantial improvement. The aim of the study was to evaluate the efficacy of induction chemotherapy with docetaxel and carboplatin followed by chemo-radiotherapy in locally advanced NSCLC. Methods: A total of 30 patients (25 males and 5 females) aged between 49–60 years (mean age 51 years) with NSCLC stage III A (10 pts) stage III B (20 pts) were enrolled in the study. Patients received docetaxel 75 mg/m 2 IV plus carboplatin AUC 5 on day 1 every 21 days for 4 cycles in combination with G-CSF. Patients then received radiotherapy (RT) at a dose 40-45 Gy depending on patients' tolerability combined with a low dose of carboplatin AUC 2 on the 1st day of each week during RT. Patients underwent CT chest and bronchoscopy before treatment and after completion of treatment to assess response and time to progression, patients with PR and SD received further 2 cycles of DC. Results: Of all patients received 4 cycles of IC were enrolled, 3 pts (10%) demonstrated CR, 9 pts (30%) had PR, 15 pts (50%) had SD and 3pts (10%) had PD. Twenty seven pts underwent CRT, 25 of these pts have completed CRT, five pts had CR, 15 pts had PR and 5pts had SD. No grade 4 toxicities were detected. The most common grade 3 toxicities were mucositis (6%), neutropenia (12%) and alopecia 50%. The median time to progression and median survival were 7 months and 9 months, respectively. Conclusions: IC with docetaxel and carboplatin followed by CRT with weekly carboplatin is feasible effective therapeutic strategy with manageable toxicity in patients with locally advanced NSCLC.
Objective measurement of sleep in mild cognitive impairment: A systematic review and meta-analysis
Authors: Angela L. D'Rozario, Julia L. Chapman, Craig L. Phillips, Jake R. Palmer, Camilla M. Hoyos, Loren Mowszowski, Shantel L. Duffy, Nathaniel S. Marshall, Ruth Benca, Bryce Mander, Ronald R. Grunstein, Sharon L. Naismith
Journal: Sleep Medicine Reviews (2020)
Results after long-term follow-up from the CAN2007 phase I/II study of weekly or twice-weekly bortezomib in patients (pts) with relapsed systemic light-chain (AL) amyloidosis.
Authors: Donna Ellen Reece, Ute Hegenbart, Vaishali Sanchorawala, Giampaolo Merlini, Giovanni Palladini, Joan Blade, Jean-Paul Fermand, Hani Hassoun, Leonard Heffner, Lixia Pei, Christopher Enny, Dixie Esseltine, Helgi Van De Velde, Andrew Cakana, Raymond Comenzo
Journal: Journal of Clinical Oncology (2013)

8545 Background: Data from multiple studies suggest that bortezomib alone or in combination regimens is active in newly diagnosed and relapsed AL. CAN2007 (NCT00298766) was the first prospective study of single-agent bortezomib in relapsed AL. Here we report outcome data at study closure after a median follow-up of 51.8 mos (median 46.1–66.1 mos). Methods: 70 pts received bortezomib 0.7, 1.0, 1.3, or 1.6 mg/m 2 on days 1, 8, 15, and 22 of 35-day cycles (QW) or 0.7, 1.0, or 1.3 mg/m 2 on days 1, 4, 8, and 11 of 21-day cycles (BIW) for up to 8 cycles (or longer in pts with evidence of ongoing clinical benefit). The maximum tolerated dose was not reached on either schedule; 18 and 34 pts were treated at the maximum planned doses of 1.6 mg/m 2 QW and 1.3 mg/m 2 BIW, respectively, and 18 pts were treated at lower doses. Post-treatment, pts were followed every 6 weeks until disease progression, and then every 3 mos for survival during the long-term follow-up phase. Results: Pts received a median (range) of 8 (1–39), 6 (1–57), and 8 (3–57) cycles of bortezomib in the 1.6 mg/m 2 QW, 1.3 mg/m 2 BIW, and lower-dose groups, respectively; overall, 32 (46%) pts received ≥8 cycles, and 4 pts were still on treatment and had received ≥39 cycles at study closure. Hematologic responses and outcomes are summarized below. Median (range) follow-up for survival was 51.8 (1–68), 46.1 (1–61), and 66.1 (2–80) mos, and 7, 12, and 9 pts have died, in the 1.6 mg/m 2 QW, 1.3 mg/m 2 BIW, and lower-dose groups, respectively. Median overall survival (OS) in all 70 pts was 62.7 mos, and 4-yr OS rate was 67.3%; data by dose group are shown below. Conclusions: Single-agent bortezomib produces durable hematologic responses and promising long-term OS data in pts with relapsed AL. Clinical trial information: NCT00298766. [Table: see text]
EPR20-075: Clinicopathological Features as a Predictor of Female Triple-Negative Breast Cancer Metastasis and Survival in the United States, 2010-2015: a Logistic Regression Model From NCI Surveillance, Epidemiology and End Results (SEER) Database
Authors: Zikun Wang, Zheyu Lu, Zhongxue Chen, Yi Dong
Journal: Journal of the National Comprehensive Cancer Network (2020)

"EPR20-075: Clinicopathological Features as a Predictor of Female Triple-Negative Breast Cancer Metastasis and Survival in the United States, 2010-2015: a Logistic Regression Model From NCI Surveillance, Epidemiology and End Results (SEER) Database" published on 20 Mar 2020 by National Comprehensive Cancer Network.
AUTOMATIC SEGMENTATION OF CARDIOVASCULAR STRUCTURES IMAGED ON CARDIAC COMPUTED TOMOGRAPHY ANGIOGRAPHY USING DEEP LEARNING
Authors: Lohendran Baskaran, Gurpreet Singh, Zhuoran Xu, Benjamin Lee, Jeong Choi, Umberto Gianni, Alexander van Rosendael, Inge J. van den Hoogen, Simon Dunham, Bobak Mosadegh, Fay Lin, Hyuk-Jae Chang, James Min, Leslee J. Shaw, Subhi Al’Aref
Journal: Journal of the American College of Cardiology (2020)
Vulnerability to Fishing and Life History Traits Correlate with the Load of Deleterious Mutations in Teleosts
Authors: Jonathan Rolland, Dolph Schluter, Jonathan Romiguier
Journal: Molecular Biology and Evolution (2020)

Understanding why some species accumulate more deleterious substitutions than others is an important question relevant in evolutionary biology and conservation sciences. Previous studies conducted in terrestrial taxa suggest that life history traits correlate with the efficiency of purifying selection and accumulation of deleterious mutations. Using a large genome data set of 76 species of teleostean fishes, we show that species with life history traits associated with vulnerability to fishing have an increased rate of deleterious mutation accumulation (measured via dN/dS, i.e., nonsynonymous over synonymous substitution rate). Our results, focusing on a large clade of aquatic species, generalize previous patterns found so far in few clades of terrestrial vertebrates. These results also show that vulnerable species to fishing inherently accumulate more deleterious substitutions than nonthreatened ones, which illustrates the potential links among population genetics, ecology, and fishing policies to prevent species extinction.
FRACTIONAL FLOW RESERVE AFTER FUNCTIONALLY OPTIMIZED CORONARY INTERVENTION (FCI) PREDICTS LONG-TERM OUTCOMES
Authors: Shiv Kumar Agarwal, Abdul Hakeem, Rimsha Hasan, Mohamed Ayan, Aisha Siraj, Mohammed Eid Madmani, Rahil Rafeedheen, Negar Salehi, Srikanth Kasula, Yalcin Hacioglu, Kristin Miller, Malek Al-Hawwas, Barry F. Uretsky
Journal: Journal of the American College of Cardiology (2020)
IMPACT OF PULMONARY HEMODYNAMICS ON CARDIAC EVENTS AFTER TRANSCATHETER AORTIC VALVE REPLACEMENT AMONG PATIENTS WITH SEVERE AORTIC STENOSIS
Authors: Garima Dahiya, Andrew Begg, Andreas Kyvernitakis, Mark Doyle, David Lasorda, Stephen Bailey, Amresh Raina, Robert Biederman, Raymond Benza
Journal: Journal of the American College of Cardiology (2020)
Presentation and treatment of HER2-positive metastatic breast cancer patients already treated with adjuvant trastuzumab.
Authors: Davis Yuri Torrejon, Serena Di Cosimo, Gessami Sanchez-Olle, Judith Balmaña, Meritxell Bellet, Patricia Gomez, Cristina Saura, Jose Manuel Perez-Garcia, Eva Muñoz-Couselo, Maria Vidal, Vanesa Ortega, Leticia De Mattos-Arruda, Mafalda Oliveira, Nuria Mulet-Margalef, Josep Tabernero, Javier Cortes
Journal: Journal of Clinical Oncology (2012)

619 Background: The introduction of trastuzumab in the clinical armamentarium has profoundly changed the natural history of HER2 positive breast cancer (BC). However, about 15% of patients with HER2 early BC treated with adjuvant trastuzumab continue to relapse. We aimed to analyze these patients with respect to clinical presentation and response to treatment. Methods: Data were retrieved from the institutional BC database of Vall d’Hebron. All the cases relapsing after exposure to adjuvant trastuzumab were analyzed. Change in expression of hormone-receptor (HR) and HER-2 status between primary tumour and corresponding local recurrence or distant metastasis was also evaluated Results: A total of 270 patients were identified. Twenty-six patients (9.6%) relapsed (Table). Overall median time from diagnosis to relapse was 27.1 months (24.1-30.1) being 29.1 months (14.3-44.1) in HR positive and 23.1 (9.9-36.2) in HR negative cases (p=0.037). Median time from last dose of trastuzumab to relapse was 7.6 (2.7-12.7) months, being 10.6 (0-27.9) and 3 months (0-7.6) in HR positive and negative cases, respectively (p=0.026). Sixteen patients have already progressed to first-line therapy with a median time to progression (TTP) of 7.4 months with no statistical difference among HR positive and HR negative (4.4 and 9.8 months, p=0.3). No difference was found in TTP to first line therapy among early (before 12 months) and delayed (after 12 months) progression on adjuvant trastuzumab. Among the 17 cases with primary tumor and matched metastatic biopsy, HER-2 negativization was detected in 2 cases; whereas a change in estrogen and progesterone receptors was seen in 17.6% and 29.4% of cases, respectively. Conclusions: Patients with HER2+/HR negative treated with adjuvant trastuzumab seems to have a significantly shorter time to relapse compared with the HER2+/HR+ tumors. In these patients biopsy of metastatic lesions might help to define the best treatment options. [Table: see text]
Planning and provision of ECMO services for severe ARDS during the COVID-19 pandemic and other outbreaks of emerging infectious diseases
Authors: Kollengode Ramanathan, David Antognini, Alain Combes, Matthew Paden, Bishoy Zakhary, Mark Ogino, Graeme MacLaren, Daniel Brodie, Kiran Shekar
Journal: The Lancet Respiratory Medicine (2020)
Abstract 13311: Myocardial Infarction in Patients With Concomitant Cancer
Authors: Fangcheng Wu, Pengyang Li, Kevin Buda, Anand Muthu Krishnan, Anil Jha, Ying Ning, Kristina X Duan, Qi Liu
Journal: Circulation (2019)

Background: Cancer is associated with hypercoagulability, which itself is associated with a higher frequency of MI. Hypothesis: We hypothesized that concomitant cancer affects therapy selection and...