tbuckley/cabot-search huggingface dataset:
Long-Term Survival after Autologous Stem Cell Transplantation in a Colombian Population
Authors: Claudia Lucia Sossa, Luis Antonio Salazar, Angela María Peña, Edgar Gomez, Claudia Marcela Chalela, David Leonardo Reyes, Manuel Rosales, Jose Sandoval-Sus, Sonia Osma, Maria Luna-Gonzalez, Sergio Serrano, Sara Ines Jimenez
Journal: Blood (2018)
Does Primary Care Add Sufficient Value to Deserve Better Funding?
Authors: Allan H. Goroll
Journal: JAMA Internal Medicine (2019)

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Abstract A042: Modulation of translation regulation by N6-methyladenosine in prostate cancer
Authors: Kellie A. Cotter, Kate D. Meyer, Matteo Benelli, Sandra Cohen, Samie Jaffrey, Francesca Demichelis, Mark Rubin
Journal: Cancer Research (2018)

Abstract Recent evidence has highlighted the role of N6-methyladenosine (m6A) in post-transcriptional control of mRNA, in particular in altering translation efficiency. The demethylase (ALKBH5) and a methyltransferase (METTL3), which control m6A placement, are down- and upregulated, respectively, in prostate adenocarcinoma (PCa). This leads to the hypothesis that PCa exhibits alterations in m6A, and by extension changes in the translation efficiency of those transcripts. In this study we seek to produce an epitranscriptome map of m6A in PCa using single-nucleotide m6A mapping (miCLIP) of benign (RWPE) and PCa (LNCaP) cell lines. Distribution of m6A marks within transcripts mimics those seen in previous datasets: most peaks map to regions in cds or 3′ UTR, and show enrichment surrounding the TSS and stop codon. Overall miCLIP identifies over 10,000 transcripts with at least one m6A in the two cell lines, with many androgen-signaling genes and oncogenes exhibiting a high number of m6A sites. In order to assess the role of m6A in alterations in translation efficiency, we combined ribosome footprint profiling with RNA-seq in cells with and without METTL3 knockdown. This analysis identified several oncogenes as targets for translational regulation by m6A along with multiple genes related to cell migration, metastasis, and integrin signaling. These results validate m6A as a potentially important additional mechanism of gene regulation at the level of translation in PCa. Further, by allowing for the identification of changes in expression at the protein level previously undetectable by gene expression analysis alone, these findings may lead to the discovery of novel biomarkers or pathways as potential targets for treatment. Citation Format: Kellie A. Cotter, Kate D. Meyer, Matteo Benelli, Sandra Cohen, Samie Jaffrey, Francesca Demichelis, Mark Rubin. Modulation of translation regulation by N6-methyladenosine in prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr A042.
Organ preservation in rectal cancer patients treated with total neoadjuvant therapy.
Authors: Rosa Maria Jimenez-Rodriguez, Felipe Fernando Quezada-Diaz, Irbaz Hameed, Sujata Patil, Jesse Joshua Smith, Julio Garcia-Aguilar
Journal: Journal of Clinical Oncology (2019)

692 Background: Retrospective case series suggest that watch-and-wait (WW) is a safe alternative to total mesorectal excision (TME) in selected patients with a clinical complete response (cCR) after chemoradiotherapy (CRT). Because treatment strategies vary widely and total numbers of patients treated at different institutions have not been reported, the proportion of rectal cancer patients who can potentially benefit from WW is not known. Here, we report the results of a treatment strategy incorporating WW in a cohort of rectal cancer patients treated with total neoadjuvant therapy (TNT). Methods: Consecutive patients with stage II/III (MRI staging) rectal adenocarcinoma treated with TNT from 2012 to 2017 by a single surgeon were included. TNT consisted of mFOLFOX6 (8 cycles) or CapeOX (5 cycles) either before or after CRT (5600 cGy in 28 fractions with sensitizing fluorouracil or capecitabine). Tumor response was assessed with a digital rectal exam, endoscopy, and MRI according to predefined criteria. Patients with a cCR were offered WW, and patients with residual tumor were offered TME. WW and TME patients were compared based on intention to treat, using the chi-square or rank sum test. Relapse-free survival (RFS) was evaluated by Kaplan-Meier analysis. Results: A total of 109 patients were identified. One patient died during CRT. Of the 108 patients, 64 (59%) had an incomplete clinical response; 4 of the 64 patients declined surgery or had local excision, and 60 underwent TME. The remaining 44 patients (41%) had a cCR and underwent WW. On average, patients in the WW group were older and had smaller, more distal tumors. Median radiation dose, number of chemotherapy cycles, number ofadverse events, or length of follow-up (28 months) did not differ between the TME and WW groups. Five (11%) of the 44 WW patients had local tumor regrowth, at a median of 14 (4–25) months after TNT; 2 of the 5 also had distant metastasis. Six (10%) of the 60 TME patients had a pathological complete response. RFS did not differ between the TME and WW groups (log rank P= 0.09). Conclusions: Approximately 40% of patients with stage II/III rectal cancer treated with TNT achieve a clinical complete response and can benefit from a WW approach with the aim of preserving the rectum.
Euro MPs back wider use of medical cannabis amid call for more research
Authors: Rory Watson
Journal: BMJ (2019)

The European Parliament has called on governments and the European Union to give more support to the use of cannabis for medicinal purposes.

In a wide ranging resolution adopted in Strasbourg on 13 February, MEPs set out a series of measures to promote official backing for medical cannabis and its wider use. They also insisted that a clear legal distinction be made between medical cannabis and use of the drug for recreational or other …
CARDIAC MYOSIN BINDING PROTEIN-C: A NEW BIOMARKER IN PATIENTS WITH ACUTE CORONARY SYNDROME
Authors: Suresh Govindan, Daniel Kahn, Rohit Sundrani, Walter P. Jeske, Jeanine Walenga, Ferdinand Leya, Debra Hoppensteadt, Jawed Fareed, Sakthivel Sadayappan
Journal: Journal of the American College of Cardiology (2012)
Dr. Jekyll and Mr. Hyde: ApoE explains opposing effects of neuronal LRP1
Authors: Michael R. Strickland, David M. Holtzman
Journal: Journal of Clinical Investigation (2019)

Alzheimer's disease (AD) is the leading cause of dementia, and its pathogenesis is initiated by the accumulation of amyloid-β (Aβ) into extracellular plaques. Apolipoprotein E4 (ApoE4) is the largest genetic risk factor for sporadic AD and contributes to AD pathogenesis by influencing clearance and seeding of the initial aggregation of Aβ. In this issue of the JCI, Tachibana et al. investigated the relationship between neuronal LRP1 expression and ApoE4-mediated seeding of Aβ and showed that knockout of neuronal LRP1 prevents the increase in Aβ pathology caused by ApoE4 expression. These findings give insight into potential therapeutic targets for the preclinical phase of AD and the pathogenesis of Aβ pathology.
Predicting Overt Hepatic Encephalopathy for the Population With Cirrhosis
Authors: Elliot B. Tapper
Journal: Hepatology (2019)

Hepatic encephalopathy (HE) is associated with poor quality of life, sharply increased mortality, repeated hospitalizations, falls, and motor vehicle accidents. HE manifests with a dynamic spectrum of severity. Overt HE is clinically obvious disorientation, even coma. Although multiple strategies are available to characterize early‐stage HE, data are limited that validate these methods in predicting overt HE, many are impractical in clinical practice, and test cutoffs relevant to the average patient clinicians manage are lacking. To accurately and efficiently classify the risk of overt HE in the population with cirrhosis, novel strategies may be needed. Herein, we review the potential competing strategies for the prediction of overt HE. Conclusion : We propose refining diagnostic cutoffs for tests that are designed to define early HE, using overt HE as a gold standard and expanding prediction tools by using measures of components from the risk pathway for HE.
A Randomized Study of Carfilzomib-Lenalidomide-Dexamethasone Vs Carfilzomib-Cyclophosphamide-Dexamethasone Induction in Newly Diagnosed Myeloma Patients Eligible for Transplant: High Efficacy in High- and Standard-Risk Patients
Authors: Delia Rota Scalabrini, Angelo Belotti, Monica Galli, Elena Zamagni, Massimo Offidani, Stefania Oliva, Vittorio Montefusco, Renato Zambello, Antonio Ledda, Mariella Grasso, Sara Aquino, Fabrizio Esma, Patrizia Tosi, Francesco Pisani, Ombretta Annibali, Anna Marina Liberati, Anna Baraldi, Piero Galieni, Giorgina Specchia, Norbert Pescosta, Katia Mancuso, Laura Paris, Rossella Ribolla, Valentina Coha, Antonio Palumbo, Pellegrino Musto, Michele Cavo, Mario Boccadoro
Journal: Blood (2017)
Diffuse Intense Intestinal FDG Activity in a Patient With Familial Adenomatous Polyposis
Authors: Liang Cai, Fuqiang Shao, Jie Zhang, Yue Chen
Journal: Clinical Nuclear Medicine (2019)

Familial adenomatous polyposis is a rare autosomal dominant intestinal syndrome with a high rate of malignant transformation. Here, we report a 20-year-old woman with a diagnosis of familial adenomatous polyposis by pathologic examination after colonoscopy biopsy, who underwent an F-FDG PET/CT to assess the extent of this disease. The images showed diffuse elevated FDG uptake along the entire colorectum. Additionally, focal enlarged lymph nodes with increased FDG uptake were noted. These findings promoted proctocolectomy and lymphadenectomy.
Aerobic exercise alleviates depressive symptoms in patients with a major non-communicable chronic disease: a systematic review and meta-analysis
Authors: Mélanie Béland, Kim L Lavoie, Samantha Briand, Una J White, Claudia Gemme, Simon L Bacon
Journal: British Journal of Sports Medicine (2019)

Objective To assess whether aerobic exercise was superior to usual care in alleviating depressive symptoms in patients living with a major non-communicable disease. Data sources Data were obtained from online databases (PubMed, PsycINFO and SPORTDiscus) as well as from reference lists. The search and collection of eligible studies was conducted up to 18 October 2018 (PROSPERO registration number CRD42017069089). Study selection We included interventions that compared aerobic exercise with usual care in adults who reported depressive symptoms (ie, not necessarily the clinical diagnosis of depression) and were living with a major non-communicable disease. Results Twenty-four studies were included in the meta-analysis (4111 patients). Aerobic exercise alleviated depressive symptoms better than did usual care (standardised mean difference (SMD)=0.50; 95% CI 0.25 to 0.76; Grading of Recommendations Assessment, Development and Evaluation: low quality). Aerobic exercise was particularly effective in alleviating depressive symptoms in cardiac patients (SMD=0.67; 95% CI 0.35 to 0.99). Conclusion Aerobic exercise alleviated depressive symptoms in patients living with a major non-communicable disease, particularly in cardiac populations. Whether aerobic exercise treats clinically diagnosed depression was outside the scope of this study.
Epithelial-to-Mesenchymal Transition Is a Mechanism of ALK Inhibitor Resistance in Lung Cancer Independent of <i>ALK</i> Mutation Status
Authors: Koji Fukuda, Shinji Takeuchi, Sachiko Arai, Ryohei Katayama, Shigeki Nanjo, Azusa Tanimoto, Akihiro Nishiyama, Takayuki Nakagawa, Hirokazu Taniguchi, Takeshi Suzuki, Tadaaki Yamada, Hiroshi Nishihara, Hironori Ninomiya, Yuichi Ishikawa, Satoko Baba, Kengo Takeuchi, Atsushi Horiike, Noriko Yanagitani, Makoto Nishio, Seiji Yano
Journal: Cancer Research (2019)

Abstract Mutations in the ALK gene are detectable in approximately 40% of ALK-rearranged lung cancers resistant to ALK inhibitors. Although epithelial-to-mesenchymal transition (EMT) is a mechanism of resistance to various targeted drugs, its involvement in ALK inhibitor resistance is largely unknown. In this study, we report that both ALK-mutant L1196M and EMT were concomitantly detected in a single crizotinib-resistant lesion in a patient with ALK-rearranged lung cancer. Digital PCR analyses combined with microdissection after IHC staining for EMT markers revealed that ALK L1196M was predominantly detected in epithelial-type tumor cells, indicating that mesenchymal phenotype and ALK mutation can coexist as independent mechanisms underlying ALK inhibitor–resistant cancers. Preclinical experiments with crizotinib-resistant lung cancer cells showed that EMT associated with decreased expression of miR-200c and increased expression of ZEB1 caused cross-resistance to new-generation ALK inhibitors alectinib, ceritinib, and lorlatinib. Pretreatment with the histone deacetylase (HDAC) inhibitor quisinostat overcame this resistance by reverting EMT in vitro and in vivo. These findings indicate that HDAC inhibitor pretreatment followed by a new ALK inhibitor may be useful to circumvent resistance constituted by coexistence of resistance mutations and EMT in the heterogeneous tumor. Significance: These findings show that dual inhibition of HDAC and ALK receptor tyrosine kinase activities provides a means to circumvent crizotinib resistance in lung cancer.
Abstract 20788: Heart Failure Readmissions and the Affordable Care Act
Authors: Vivian G Dicks, Madison Gates, Won Suk Yoo
Journal: Circulation (2017)

Introduction: Heart failure (HF) readmissions have been associated with lack of access to care, including health insurance and affordability. The focus of the Affordable Care Act (ACA) was to reduce cost as a barrier to care. Monitoring the trends in readmission rates is an important measure of patient care outcomes. Hypothesis: The ability of receiving health care based on insurability will reduce the burden of heart failure readmissions through the measures implemented during the ACA. Methods: Descriptive and multivariate analyses were performed utilizing the Healthcare Cost and Utilization Project (HCUP) on-line National Inpatient Readmission database to compare the 2009 and the 2013 hospital readmissions for HF. Results: The study cohort consisted of weighted national estimates of 81,780 HF readmissions for 2009 compared to 65,458 HF readmissions in 2013. Overall readmissions declined by 20% (CI ± 0.038). Individuals that were uninsured had the least decline at 5.6% (CI ± 0.47) and those on Medicaid a...
Effects of promoter methylation on tissue inhibitor of metalloproteinases-2 (TIMP-2) expression in prostate cancer
Authors: Sai Murali Pulukuri, Sanjeeva Mohanam, Jasti S. Rao
Journal: Cancer Research (2006)

1585   Tumor invasion and metastasis are known to involve a complex series of integrated events consisting of tumor cell adhesion, extracellular matrix (ECM) proteolysis, and cell migration within the surrounding microenvironment. The tissue inhibitors of metalloproteinases (TIMPs) are a family of four secreted inhibitors of matrix metalloproteinases (MMPs). Because TIMPs play a significant role in suppressing tumor growth, angiogenesis, invasion and metastasis, we first examined the levels of TIMPs and MMPs in normal prostate epithelial cells as well as prostate cancer cell lines with varying metastatic potentials using reverse transcription PCR, immunoblot analysis, zymography and reverse zymography. The results of our experiments demonstrated a strong inverse correlation between TIMP and MMP (e.g., MMP-9 and MMP-2) protein levels and the invasive ability of normal and prostate cancer cells. Detectable levels of TIMPs were observed only in normal prostate epithelial cells, but not in metastatic prostate cancer cell lines LNCaP, DU145, PC3 and Tramp-C1. However, the molecular mechanisms underlying the differential expression of TIMPs in prostate cancer remains elusive. Here, we studied the mechanism of TIMP-2 expression in prostate cancer cell lines using methylation-specific PCR to analyze the methylation status of the promoter region of the TIMP-2 gene. We found the methylated CpG island in the TIMP-2 promoter in the metastatic prostate cancer cell lines LNCaP, DU145, PC3 and Tramp-C1, but not in TIMP-2-expressing normal prostate epithelial cell line RWPE1, which contains an unmethylated CpG island in the TIMP-2 promoter region. Furthermore, the expression of TIMP2 was restored after treatment with epigenetic silencing modifiers 5-aza and TSA. These results show, for the first time, that TIMP2 expression is regulated in part by promoter methylation in prostate cancer cells. Moreover, the restoration of TIMP-2 expression in highly metastatic prostate cancer cell lines DU145 and PC3 resulted in a significant reduction of tumor cell invasion as indicated by a matrigel invasion assay. Together, these results suggest an inverse expression pattern of MMP-9/MMP-2 and TIMP-2. Promoter methylation of TIMP-2 is a novel epigenetic event in the complex, multi-step process of prostate cancer progression and may contribute to a malignant phenotype. Because TIMP-2 was only expressed by normal prostate cells, silencing of its expression might be an effective molecular indicator of prostate cancer metastasis.
Abstract 14217: Clinical Predictive Models for Sudden Cardiac Arrest: A Systematic Review of the Literature
Authors: William A Janes, Christine Lundquist, Rebecca Lorenzana, Teresa May, Christopher Madias, Benjamin S Wessler, David M Kent
Journal: Circulation (2017)

Objectives: Myriad Clinical Predictive Models (CPMs) have been developed to predict outcomes following cardiac arrest (CA); however, the relative performance of these models is largely unknown. We ...
Abstract 16050: S3 Heart Sound Amplitudes Measured by Accelerometer Reflect Auscultated S3 Heart Sound Volume Grades
Authors: Michael Cao, Roy Gardner, Ramesh Hariharan, Devi Nair, Christopher Schulze, Qi An, Pramod Thakur, John Boehmer
Journal: Circulation (2017)

Introduction: The third heart sound (S3) is regarded as one of the earliest signs of heart failure (HF) and is typically assessed via auscultation clinically. The embedded accelerometer sensor in i...
Checkpoint Kinase 1 Inhibition Enhances Cisplatin Cytotoxicity and Overcomes Cisplatin Resistance in SCLC by Promoting Mitotic Cell Death
Authors: Wei-Hsun Hsu, Xiaoliang Zhao, Jianquan Zhu, In-Kyu Kim, Guanhua Rao, Justine McCutcheon, Shuo-Tse Hsu, Beverly Teicher, Bhaskar Kallakury, Afshin Dowlati, Yu-Wen Zhang, Giuseppe Giaccone
Journal: Journal of Thoracic Oncology (2019)
Abstract 10900: Persistent Alterations in Energy Metabolism and Oxygen Consumption Following Cardiac Arrest
Authors: Koichiro Shinozaki, Josha W. Lampe, Junhwan Kim, Tong Da, Tai Yin, Lance B. Becker
Journal: Circulation (2015)

Introduction: Although metabolic problems after cardiac arrest (CA) have been postulated, the actual measurement of metabolic alterations after CA remain undescribed. The measurement of oxygen extraction (VCO2), carbon dioxide excretion (VCO2), and respiratory quotient (RQ), reflect the energy metabolism and may provide insight into the post-arrest metabolism. Objective: To investigate metabolism alterations after CA, which may be detected via changes in VCO2, VO2, and RQ. Secondarily to test whether it is affected by therapeutic temperature management (TTM) Methods: Sixteen male rats underwent a protocol for 10 minutes of asphyxial CA and return of spontaneous circulation (ROSC). Three groups were compared: Group1: controls (no-CA, n=5), group2: CA (n=6), and group3: CA with TTM (n=5). Within the TTM group, the body was cooled to 33 °C. Capnography was recorded and O2 extraction was measured for 120min to measure VCO2 and VO2. RQ was the ratio of VCO2/VO2. Results: The post arrest VCO2 was 1.5 fold higher in the CA group than in the controls (17.3±2.2mL/kg/min versus 11.2±1.0mL/kg/min, p&lt;.01) in minutes 20 through 60. The VCO2 value in CA was normalized after 60min. VCO2 (12.5±1.3 mL/kg/min, p&lt;.01) in TTM-treated CA was significantly lower than untreated CA. The post arrest VO2 was greater in the CA group than in the controls, starting 15min after ROSC, and gradually increased to an extraction rate 2.1 fold higher (29.8±6.0mL/kg/min) than controls (14.1±1.6mL/kg/min, p&lt;.01). There were no differences in VO2 between TTM-treated and untreated CA. RQs in TTM-treated and untreated CA were significantly and persistently lower than controls (0.5±0.1, 0.5±0.1 vs. 0.9±0.1, p&lt;.01). Conclusions: VO2 in rats after CA was markedly elevated after ROSC and RQ decreased to extremely low levels. VCO2 showed some attenuation by TTM, however surprisingly TTM did not affect VO2 or RQ. These results suggest that profound alterations in oxygen extraction occur after CA and may be measured non-invasively in patients. The finding of a lowered RQ has not be described previously, appears to be driven by increased VO2, and may be due to non-CO2 generating oxygen utilization. If true, this may have great importance for mechanism, monitoring, and customized treatment of CA.
Pilot Study of Tocilizumab in Patients with HIV and Symptomatic Kaposi Sarcoma Herpesvirus (KSHV)-Associated Multicentric Castleman Disease
Authors: Ramya Ramaswami, Kathryn Lurain, Anaida Widell, Mark N. Polizzotto, Priscila H. Goncalves, Matthew Lindsley, Seth M. Steinberg, Denise Whitby, Thomas S. Uldrick, Robert Yarchoan
Journal: Blood (2018)
Dissecting the Epigenetic Landscape of Smoldering, Newly Diagnosed and Relapsed Multiple Myeloma Revealed IRAK3 As a Marker of Disease Progression
Authors: Mahshid Rahmat, Nicholas Haradhvala, Romanos Sklavenitis-Pistofidis, Jihye Park, Daisy Huynh, Mark Bustoros, Brianna Berrios, Mairead Reidy, Adriana Perilla-Glen, Bradley Rivotto, Kalvis Hornburg, David M. Dorfman, Jonathan D. Licht, Gad Getz, Irene M. Ghobrial
Journal: Blood (2018)