tbuckley/cabot-search huggingface dataset:
Palliative Care for Patients With Opioid Misuse
Authors: David Hui, Joseph Arthur, Eduardo Bruera
Journal: JAMA (2019)

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TNF induces production of type 2 cytokines in human group 2 innate lymphoid cells
Authors: Noriko Ogasawara, Julie A. Poposki, Aiko I. Klingler, Bruce K. Tan, Kathryn E. Hulse, Whitney W. Stevens, Anju T. Peters, Leslie C. Grammer, Kevin C. Welch, Stephanie S. Smith, David B. Conley, Ken-ichi Takano, Tetsuo Himi, Robert C. Kern, Robert P. Schleimer, Atsushi Kato
Journal: Journal of Allergy and Clinical Immunology (2019)
Cooperative Effects of a Dnmt Inhibitor and All-Trans Retinoic Acid in an AML Cell Line Model Lacking PML-Rara
Authors: Ruth Meier, Gabriele Greve, Christoph Niemöller, Heiko Becker, Tobias Ma, Ralitsa Langova, Björn Grüning, Lars Feuerbach, Daniel B. Lipka, Justus Duyster, Benedikt Brors, Christoph Plass, Michael Lübbert
Journal: Blood (2018)
Unstable Genome and Transcriptome Dynamics during Tumor Metastasis Contribute to Therapeutic Heterogeneity in Colorectal Cancers
Authors: Sung-Yup Cho, Jeesoo Chae, Deukchae Na, Wonyoung Kang, Ahra Lee, Seoyeon Min, Jinjoo Kang, Boram Choi, Jieun Lee, Chang Ohk Sung, Jeffrey H. Chuang, Charles Lee, Won-Suk Lee, Hansoo Park, Jong-Il Kim
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Genomic and transcriptomic alterations during metastasis are considered to affect clinical outcome of colorectal cancers, but detailed clinical implications of metastatic alterations are not fully uncovered. We aimed to investigate the effect of metastatic evolution on in vivo treatment outcome, and identify genomic and transcriptomic alterations associated with drug responsiveness. Experimental Design: We developed and analyzed patient-derived xenograft (PDX) models from 35 patients with colorectal cancer including 5 patients with multiple organ metastases (MOMs). We performed whole-exome, DNA methylation, and RNA sequencing for patient and PDX tumors. With samples from patients with MOMs, we conducted phylogenetic and subclonal analysis and in vivo drug efficacy test on the corresponding PDX models. Results: Phylogenetic analysis using mutation, expression, and DNA methylation data in patients with MOMs showed that mutational alterations were closely connected with transcriptomic and epigenomic changes during the tumor evolution. Subclonal analysis revealed that initial primary tumors with larger number of subclones exhibited more dynamic changes in subclonal architecture according to metastasis, and loco-regional and distant metastases occurred in a parallel or independent fashion. The PDX models from MOMs demonstrated therapeutic heterogeneity for targeted treatment, due to subclonal acquisition of additional mutations or transcriptomic activation of bypass signaling pathway during tumor evolution. Conclusions: This study demonstrated in vivo therapeutic heterogeneity of colorectal cancers using PDX models, and suggests that acquired subclonal alterations in mutations or gene expression profiles during tumor metastatic processes can be associated with the development of drug resistance and therapeutic heterogeneity of colorectal cancers.
Safety and Tolerability of a Novel Peptide-Based Immunotherapy for Peanut Allergy
Authors: Sara R. Prickett, Pascal LC. Hickey, Judy Bingham, Tracy Phan, Jodie Abramovitch, Jennifer M. Rolland, William B. Smith, Mark Hew, Robyn E.O. Hehir
Journal: Journal of Allergy and Clinical Immunology (2019)
Exploiting Exosomes in Cancer Liquid Biopsies and Drug Delivery
Authors: Coy Austin Fitts, Nan Ji, Yusheng Li, Chalet Tan
Journal: Advanced Healthcare Materials (2019)

Abstract Exosomes are cell‐derived nanovesicles that transfer molecular cargo from donor to recipient cells and mediate intercellular communication. Advancement in elucidating the biological capabilities and functionalities of exosomes has revealed the striking roles of exosomes as conveyors of bioactive molecules across the biological barriers. Tumor‐derived exosomes hold great promise to serve as a liquid biopsy tool for cancer diagnosis and prognosis, as large quantities of exosomes are excreted by tumor cells continuously into the circulation, carrying the molecular cargo (DNA, RNA, proteins) reflective of the genetic and signaling alterations in tumor cells. Two inherent characteristics of exosomes offer important opportunities for drug delivery: their superb transcellular permeability and biocompatibility. Exosomes are uniquely capable of encapsulating a variety of payloads and deliver them to the target tissues. This review discusses the potential of tumor‐derived exosomes in cancer liquid biopsies as well as the underlying mechanisms. Furthermore, the recent progress of developing exosomes as highly versatile and efficient drug carriers is also summarized.
Prospective analysis of microRNA 31-3p (miR31-3p) as a predictive biomarker of response to anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibodies (mABs) in patients with metastatic colorectal cancer (mCRC).
Authors: Gayathri Anandappa, Andrea Lampis, David Cunningham, Kyriakos Kouvelakis, Khurum Khan, George Vlachogiannis, Nina Tunariu, Sheela Rao, David Watkins, Naureen Starling, Chiara Braconi, Clare Peckitt, Janet Thomas, Isma Rana, Ruwaida Begum, Annette Bryant, Jens Hahne, Ian Chau, Matteo Fassan, Nicola Valeri
Journal: Journal of Clinical Oncology (2019)

548 Background: RAS status in tissue and/or liquid biopsies and tumour location (sidedness) are predictive markers of patients’ response to anti-EGFR mABs. MiR-31-3p expression has been correlated with clinical benefit from anti-EGFR mABs with chemotherapy. We aimed to validate the predictive power of miR-31-3p in a prospective cohort of chemo-refractory mCRC patients treated with single agent anti-EGFR mABs in the PROSPECT-C trial (NCT02994888). Methods: MiR-31-3p was tested by in-situ hybridization in 91 pre-treatment (PT) core biopsies from 45 mCRC patients. Sequential tissue biopsies obtained PT, at time of best response and at disease progression were tested to monitor changes in miR-31-3p expression over treatment. In 34 patients miR-31-3p, gender, sidedness, previous lines of treatment and RAS status in PT cell free (cf) DNA were evaluated in multivariate Cox and logistic regression models. Results: Patients with low miR-31-3p expression in PT biopsies showed better overall response rate (ORR: 58.3% vs 22.2%), median progression free survival (mPFS: 4.21 vs 2.27 months) and overall survival (mOS: 4.21 vs 2.27 mo) compared to those with high miR-31-3p expression (Hazard Ratio for PFS high vs low: 1.96; 95% CI: 0.98-3.88; p: 0.06 and HR for OS high vs low: 2.14; 95% CI: 1.04- 4.40; p: 0.04) adjusting for age, gender and sidedness. There was significant association between ORR and miR-31-3p expression (χ 2 test p: 0.029). MiR-31-3p expression was an independent predictor of response, adjusting for gender, previous treatment lines and RAS (odds ratio: 0.14; 95% CI: 0.02-1.00, p: 0.048). A trend towards improved mPFS (5.10 vs 2.27 mo) and mOS (15.23 vs 4.67 mo) was noted in miR31-3p low vs high group in cfDNA RAS wild-type patients. No significant change in miR-31-3p expression were observed in archival tissue and sequential tissue biopsies. Conclusions: Our study validates the role of miR-31-3p as potential predictive biomarker of selection for anti-EGFR mABs. Further studies are needed to test if miR-31-3p combined with cfDNA RAS test can identify best responders in specific clinical niches.
Abstract 243: Pulsatile Versus Nonpulsatile Emergency Cardiopulmonary Bypass: Impact on Early Regional Brain Perfusion After Lethal Cardiac Arrest in Rats
Authors: Manuel Boller, Sung Koo Jung, Tai Yin, Lance Becker
Journal: Circulation (2012)

Background: An increasing amount of clinical data suggests that emergency cardiopulmonary bypass (ECPB) is an effective tool for resuscitation from prolonged cardiac arrest. Next to controlling pharmacological components of the reperfusate, ECPB also allows definition of physical characteristics of reperfusion. Pulsatile reperfusion is a intriguing strategy but has not been studied in the setting of ECPB despite its technical feasibility. Thus we aimed at testing the influence of a pulsatile reperfusion component to early brain perfusion after lethal cardiac arrest in a rodent ECPB model. Methods: After anesthesia and instrumentation, male Sprague-Dawley rats (448±41g) underwent 20 min of untreated asphyxial arrest and were resuscitated with normothermic ECPB with either pulsatile (150 beats/min; 50 mL/min; n=8) or non-pulsatile flow (50 mL/min; n=8). No vasopressors were administered. ROSC was prevented by occluding the right ventricle. At 3 min, FITC-dextran 70 was injected into the bypass circuit. Two minutes later ECPB was stopped, the brain removed and brain slices at defined levels (Bregma -0.3 mm, -1.4 mm, -3.3 mm, -11.3 mm) mounted for fluorescent microscopy and blinded quantification of the area of FITC-stained perfused cerebral microvessels. Perfused areas were quantified for the whole brain, cortex, caudate putamen and hippocampus. Results: The overall perfused cortical area (41±13%) was significantly higher than the non-cortical area (20±11%), with a trend towards better perfusion with pulsatile bypass in the deeper brain regions (p=0.07). While no differences in mean arterial blood pressure (MAP) between groups were present, perfused areas in putamen (p=0.04) and hippocampus (p=0.03) were significantly higher in animals treated with pulsatile ECPB. Conclusions: The data suggests that pulsatile ECPB may be of benefit to improve perfusion of deeper brain regions after prolonged cardiac arrest and especially of those areas known to be vulnerable to cerebral hypoxia/ischemia. Additional studies are warranted to further define the role of pulsatile ECPB for resuscitation from lethal cardiac arrest.
Understanding the experience of sleep disturbance in psoriasis: a qualitative exploration using the Common‐Sense Model of Self‐Regulation
Authors: A.L. Henry, C. Bundy, S.D. Kyle, C.E.M. Griffiths, A. Chisholm
Journal: British Journal of Dermatology (2019)

Psoriasis is associated with significant morbidity, which negatively impacts upon quality of life. Sleep disturbance is reported to be common in patients with psoriasis and is associated with physical and psychological variables, although there is little published work in this area. Understanding sleep and the factors involved in its disturbance in psoriasis is a potentially important clinical area given the role of sleep in health and disease processes. To explore the experience of sleep and sleep disturbance in psoriasis using the Common‐Sense Model of Self‐Regulation (CS‐SRM). Semistructured interviews were conducted with adults diagnosed with psoriasis. Interview questions were informed by the CS‐SRM and previous research. Framework analysis was applied, including coding data into the CS‐SRM dimensions and allowing additional inductive themes to emerge. Seventeen people with psoriasis (nine women, eight men; aged 19–86 years) were interviewed about sleep and sleep disturbance. Seven themes emerged, with six accounted for by the CS‐SRM: characteristics of sleep disturbance, change in sleep patterns, thoughts about and symptoms of disease disturbing sleep, impact of poor sleep on daily life, attempts to improve sleep, a daily battle for control and a seventh relating to metacognitive processes. A reciprocal relationship between sleep and psoriasis was evident across themes with interactions between key sleep‐related thoughts, emotions and behaviours. This study showed that sleep disturbance is a persistent concern for people with psoriasis; it has a 24‐h impact, and interacts with the psychological and physical aspects of psoriasis. The distress and frustration felt when managing sleep disturbance perpetuated problematic sleep. Addressing this with currently available sleep treatments may therefore confer sleep and psoriasis‐related benefits for people living with this condition.
MYC Pathway Activation Is Frequently Observed in Treatment-Naive CLL and Defines a Subgroup with Particular Benefit from the Addition of Rituximab to Chemotherapy
Authors: Johannes Bloehdorn, Julia Krzykalla, Billy Michael Chelliah Jebaraj, Karlheinz Holzmann, Jasmin Bahlo, Sandra Robrecht, Kathryn Humphrey, Michael Wenger, Eugen Tausch, Christof Schneider, Lars Bullinger, Kirsten Fischer, Michael Hallek, Daniel Mertens, Axel Benner, Hartmut Döhner, Stephan Stilgenbauer
Journal: Blood (2018)
Abstract 197: Heat Shock Factor 1 Enhances Therapeutic Potential of c-kit+ Cardiac Progenitor Cells Derived Exosomes
Authors: Sudhish Sharma, Grace E Bigham, Rachana Mishra, Laxminarayana Korutla, Prashanth Vallabhajosyula, Sotirios Karanthasis, Sunjay Kaushal
Journal: Circulation Research (2017)

Background: Cardiac Progenitor cells (CPCs, identified by ckit+/CD45-/lin-) are being studied in 21 clinical trials (recruiting and completed) to restore heart function and promote tissue regeneration in response to injury. We have recently identified that CPCs derived exosomes (EXO) are critical for their functional activity. Hypothesis: We hypothesized that heat shock factor 1 (HSF1) modulates EXO biogenesis from CPCs and their enrichment with therapeutic miRs. Methods and Results: EXOs were isolated from cultured CPCs, generated from the biopsies of right atrial appendage (RAA) at the time of cardiac surgery from neonatal (nCPCs, &lt; 1 month) and adult (aCPCs, &gt; 40 years) patients with normal functioning myocardium using size exclusion chromatography (CL-2B). EXOs were analyzed by transmission electron microscopy, Nanosight (LM10) and the flow cytometry for EXO markers as CD63 and ALIX. Our results showed that chronological ageing affects EXOs biogenesis and their functional potential since nCPCs generate significantly more EXOs than aCPCs. HSF1 overexpression in aCPCs significantly enhanced their EXO biogenesis. nCPCs derived EXOs (nEXOs) are significantly more effective (nEXOs 62.14±2.9% vs aEXO 56 ± 3.6%, p&lt;0.05) to improve cardiac function and tissue repair in a myocardial infarction (MI) model in rats as compared to aCPCs derived EXOs. In a rat MI model, using florescent labelled HLA-A antibodies, nEXOs were retained for longer duration in rat serum as compared to aEXOs, which correlated with myocardial functional recovery. miRNA sequencing of EXOs identified significantly higher expression of cardio protective miRs like miR199b, 146a, 454, 590, 21 in nEXOs as compared to aEXOs. We also identified that HSF1 overexpression in aCPCs significantly enriched them with miR21 and miR590, suggesting that HSF1 can affect EXO biogenesis and its miR Cargo. Conclusion: We showed that nEXOs are functionally more active and modulation of HSF1 can affect EXOs biogenesis and its cargo from CPCs. These results also suggest that nEXOs has the potential to be utilized as an off the shelf cell-free therapy.
Phase I Trial of Carfilzomib + R-CHOP (CarR-CHOP) for Frontline Treatment of Patients with Diffuse Large B-Cell Lymphoma (DLBCL)
Authors: Brian T. Hill, Robert M. Dean, Deepa Jagadeesh, Alex V. Mejia Garcia, Brad Pohlman, Allison M. Winter, Ethan Krauspe, Patrick Collier, Christopher D'Andrea, Ashley Morrison, Sarah Lehmann, Benjamin K. Tomlinson, Brenda Cooper, Marcos de Lima, Sarah L. Ondrejka, Eric D. Hsi, Paolo Caimi
Journal: Blood (2018)
Abstract 14052: Evaluation of Obesity Paradox After Atrial Fibrillation Ablation
Authors: Karam Ayoub, Meera Marji, Bassam Ayoub, Bilal Alqam, Fuad Habash, Waddah Maskoun
Journal: Circulation (2017)

Abstract: We aim to explore the effect of obesity in real-world outcomes after catheter ablation (CA) of atrial fibrillation (AF). Background: Obesity is a major risk factor for cardiovascular dise...
Abstract 16007: Incremental Value of Broadly Available Electrocardiographic Markers in Prediction of Sudden Cardiac Arrest
Authors: Aapo L Aro, Kyndaron Reinier, Carmen Teodorescu, Audrey Uy-Evanado, Navid Darouian, Derek Phan, Jonathan Jui, Elsayed Z Soliman, Larisa G Tereshchenko, Sumeet S Chugh
Journal: Circulation (2016)

Introduction: Sudden cardiac arrest (SCA) is a major public health concern, but effective risk stratification tools are lacking. 12-lead ECG is an attractive means for risk stratification due to lo...
Abstract 013: A Model for Stroke Prediction Using Claims Data in a Contemporary Cohort of Patients With Atrial Fibrillation Receiving Oral Anticoagulation
Authors: J'Neka S Claxton, Richard F MacLehose, Pamela L Lutsey, Faye L Norby, Lin Y Chen, Wesley T O'Neal, Alanna M Chamberlain, Lindsay G Bengtson, Alvaro Alonso
Journal: Circulation (2018)

Background: Oral anticoagulants (OACs) are recommended for AF patients for the prevention of thromboembolic events, including stroke. Stroke risk stratification scores (e.g., CHA 2 DS 2 -VASc) are used to tailor therapeutic recommendations for patients in different risk groups. However, these were derived before the advent of direct OACs. At present, there is no tool that estimates a patient’s stroke risk, given their individual characteristics, by type of OAC. Methods: We used healthcare utilization data from two independent US databases (MarketScan and Optum) to construct and validate a predictive model of ischemic stroke in patients with AF initiating OACs. Patients with non-valvular AF initiating OACs were identified from the MarketScan data for years 2007-2015. Using bootstrapping methods and backward selection of 44 candidate variables, we developed a model which selected variables predicting stroke. The final model was validated in patients with non-valvular AF in the Optum Clinformatics database in the period 2009-2015. Results: Among 135,523 patients with AF initiating OAC in the MarketScan dataset, 2,028 experienced an ischemic stroke after anticoagulant initiation. The stepwise model identified 15 variables (including type of OAC) associated with ischemic stroke (Table). The discrimination (c-statistic) of the model was adequate [0.68, 95% confidence interval (CI) 0.66-0.70], showing excellent calibration (χ 2 = 7.7 p=0.57). The model was then applied to the 84,549 AF patients in the Optum data set (1408 stroke events). The model showed similar discrimination (c-statistic 0.67, 95%CI 0.65-0.70) and calibration (χ 2 = 12.8 p=0.17). However, previously-developed predicted models had similar discriminative ability (CHA 2 DS 2 -VASc 0.67, 95%CI 0.65-0.68; ATRIA 0.67, 95%CI 0.65-0.68) Conclusion: A novel model using extensive administrative healthcare data for the identification of patients at higher risk of ischemic stroke by type of anticoagulant did not perform better than established simple models.
Chemotherapy-induced neutropenia as a prognostic factor in patients with unresectable pancreatic cancer treated with gemcitabine and nab-paclitaxel.
Authors: Motoyasu Kan, Hiroshi Imaoka, Masafumi Ikeda, Shuichi Mitsunaga, Izumi Ohno, Yusuke Hashimoto, Mitsuhito Sasaki, Hideaki Takahashi, Kazuo Watanabe, Kumiko Umemoto, Gen Kimura, Taro Shibuki
Journal: Journal of Clinical Oncology (2019)

324 Background: Chemotherapy-induced neutropenia (CIN) has been reported to be associated with a longer survival in patients with various cancers. The aim of our study was to assess whether CIN could also be a prognostic factor in patients with unresectable pancreatic cancer receiving treatment with gemcitabine (GEM) and nab-paclitaxel (nab-PTX). Methods: We retrospectively analyzed the medical records of pancreatic cancer patients who had been treated with GEM and nab-PTX as first-line chemotherapy. CIN was categorized on the basis of the worst WHO grade during chemotherapy: absent/mild (≦ grade 2), or severe (≧ grade 3). The background characteristics and CIN as time-varying covariates (TVCs) were analyzed as potential prognostic factors using a Cox proportional hazards model. Results: We analyzed a total of 291 patients (absent/mild CIN: 116 patients; severe CIN: 174 patients). The median time to severe CIN was 14 days (interquartile range: 10–39 days). The median overall survival (OS) was significantly longer in the severe CIN group than in the absent/mild CIN group (19.2 vs. 11.3 months; p &lt; 0.001) After adjustments, severe CIN was identified as an independent predictor of the OS (HR, 0.54; 95% CI, 0.38–0.77; p = 0.001). In the TVC model also, severe CIN was identified as an independent factor (HR, 0.79; 95% CI, 0.68–0.92; p = 0.002). Conclusions: Severe CIN was associated with a longer survival in patients with pancreatic cancer treated with GEM and nab-PTX.
A Randomized Prospective Study to Assess the Effect of Vitamin E on Peroxiredoxin- 2 As a Novel Antioxidant Marker in Young Beta-Thalassemia Major Patients on Different Chelation Therapy
Authors: Mohamed Abd el mohsen, Maha Saber, Amira Adly, Eman Ismail, Omar Elalfy, Elghamry Islam, Fatma Ibrahim, Mohsen Saleh Elalfy
Journal: Blood (2018)