tbuckley/cabot-search huggingface dataset:
B‐type natriuretic peptide trend predicts clinical significance of worsening renal function in acute heart failure
Authors: Nicholas Wettersten, Yu Horiuchi, Dirk J. van Veldhuisen, Christian Mueller, Gerasimos Filippatos, Richard Nowak, Christopher Hogan, Michael C. Kontos, Chad M. Cannon, Gerhard A. Müeller, Robert Birkhahn, Pam Taub, Gary M. Vilke, Olga Barnett, Kenneth McDonald, Niall Mahon, Julio Nuñez, Carlo Briguori, Claudio Passino, Patrick T. Murray, Alan Maisel
Journal: European Journal of Heart Failure (2019)
Storage-Induced Micro-Erythrocytes Are Rapidly Cleared from Recipient Circulation and Predict Transfusion Recovery
Authors: Camille Roussel, Alexandre Morel, Michaël Dussiot, Mickael MARIN, Martin Colard, Aurélie Fricot, Anaïs Martinez, Charlotte Chambrion, Benoît Henry, Geoffroy Volle, Mallorie Depond, Safi Dokmak, Francois Paye, Alain Sauvanet, Caroline Le Van Kim, Yves Colin Aronovicz, Steven L. Spitalnik, Papa Alioune Ndour, Eldad A. Hod, Olivier Hermine, Pierre Buffet, Pascal Amireault
Journal: Blood (2019)
Autophagy modulators for the treatment of oral and esophageal squamous cell carcinomas
Authors: Tuhina Khan, Nicola Relitti, Margherita Brindisi, Stefania Magnano, Daniela Zisterer, Sandra Gemma, Stefania Butini, Giuseppe Campiani
Journal: Medicinal Research Reviews (2019)

Abstract Oral squamous cell carcinomas (OSCC) and esophageal squamous cell carcinomas (ESCC) exhibit a survival rate of less than 60% and 40%, respectively. Late‐stage diagnosis and lack of effective treatment strategies make both OSCC and ESCC a significant health burden. Autophagy, a lysosome‐dependent catabolic process, involves the degradation of intracellular components to maintain cell homeostasis. Targeting autophagy has been highlighted as a feasible therapeutic strategy with clinical utility in cancer treatment, although its associated regulatory mechanisms remain elusive. The detection of relevant biomarkers in biological fluids has been anticipated to facilitate early diagnosis and/or prognosis for these tumors. In this context, recent studies have indicated the presence of specific proteins and small RNAs, detectable in circulating plasma and serum, as biomarkers. Interestingly, the interplay between biomarkers (eg, exosomal microRNAs) and autophagic processes could be exploited in the quest for targeted and more effective therapies for OSCC and ESCC. In this review, we give an overview of the available biomarkers and innovative targeted therapeutic strategies, including the application of autophagy modulators in OSCC and ESCC. Additionally, we provide a viewpoint on the state of the art and on future therapeutic perspectives combining the early detection of relevant biomarkers with drug discovery for the treatment of OSCC and ESCC.
Neutrophil-to-lymphocyte ratio is a useful biomarker for predicting worse clinical outcome in chemo-resistant urothelial carcinoma patients treated with pembrolizumab
Authors: K. Ogihara, E. Kikuchi, T. Okabe, S. Hattori, R. Yamashita, S. Yoshimine, S. Shirotake, K. Matsumoto, R. Mizuno, S. Hara, M. Oyama, M. Niwakawa, M. Oya
Journal: Annals of Oncology (2019)
The chances of hepatic resection curing hepatocellular carcinoma
Authors: Alessandro Cucchetti, Jianhong Zhong, Sarah Berhane, Hidenori Toyoda, KeQing Shi, Toshifumi Tada, Charing C.N. Chong, Bang-De Xiang, Le-Qun Li, Paul B.S. Lai, Giorgio Ercolani, Vincenzo Mazzaferro, Masatoshi Kudo, Matteo Cescon, Antonio Daniele Pinna, Takashi Kumada, Philip J. Johnson
Journal: Journal of Hepatology (2019)
Abstract 28: Feasibility and Safety of Pre-Hospital Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) in Non-Traumatic Out-Of-Hospital Cardiac Arrest
Authors: Jostein R Brede, Thomas Lafrenz, Pål Klepstad, Eivinn A Skjærseth, Trond Nordseth, Edmund Søvik, Andreas J Kruger
Journal: Circulation (2019)

Introduction: The proportion of patients surviving to hospital discharge after out of hospital cardiac arrest (OHCA) is low and any measure that may improve circulation to vital organs during cardiopulmonary resuscitation (CPR) is beneficial. The use of resuscitative endovascular balloon occlusion of the aorta (REBOA) will redistribute cardiac output to the organs proximal to the occlusion. Animal studies supports that aortic occlusion during CPR might benefit patients suffering from OHCA, but human data are scarce. Methods: We performed an observational study at the helicopter emergency medical service in Trondheim (Norway) to assess the feasibility and safety of establishing REBOA in OHCA patients. The femoral artery was identified by ultrasound and a REBOA catheter was placed in the thoracic aorta. All patients received advanced cardiac life support (ACLS) during the procedure. REBOA eligibility, procedural success and time intervals were registered. A safety monitoring program was conducted to ensure that the procedure did not interfere with the quality of ACLS. Results: REBOA was initiated in ten of 98 OHCA patients. The mean age was 63 years (55-71) and 7 were male. The REBOA procedure was successful in all cases (100%), with 80% success rate on first cannulation attempt. Mean REBOA procedural time was 11,7 minutes (8-16, SD 3,2). End-tidal CO2 (EtCO2) increased by a mean of 1.9 kPa at 60 seconds after inflation compared to baseline (p &lt; 0.001). Six of 10 patients (60%) achieved return of spontaneous circulation, 3 (30%) was admitted to hospital. 30-day survival was 10%. The mean width of the femoral artery and vein during CPR was 5,9 mm (3,6 - 7,4, SD 1,2) and 9,4 mm (5,0 - 12,9, SD 2,9), respectively. The safety monitoring group identified no negative influence on the ACLS quality. Conclusions: This is the first study to assess the pre-hospital use of REBOA in patients with non-traumatic cardiac arrest. The REBOA procedure does not interfere with the quality of the ACLS. REBOA is a feasible adjunct treatment in OHCA. The significant increase in EtCO2 after occlusion suggests improved organ circulation during CPR.
A nonepidermolytic keratinocytic epidermal naevus associated with a postzygotic mutation in the gene encoding epidermal growth factor receptor
Authors: N. Umegaki‐Arao, N. Ono, R. Tanaka, T. Sasaki, H.  Fujita, A. Shiohama, S. Aoki, M. Amagai, A.  Kubo
Journal: British Journal of Dermatology (2019)
Impact of Adding Melphalan to Fludarabine and a Myeloablative Dose of Intravenous Busulfan for Patients Who Received Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Yoshimitsu Shimomura, Masahiko Hara, Hisashi Yamamoto, Tatsuo Ichinohe, Takahiro Fukuda, Minoko Takanashi, Yoshiko Atsuta, Takayuki Ishikawa
Journal: Blood (2019)
Development of a Novel Inflammation-Based Index for Hepatocellular Carcinoma
Authors: Stephen Lam Chan, Lin-Lee Wong, Kwan-Chee Allen Chan, Chit Chow, Joanna Hung-Man Tong, Terry Cheuk-Fung Yip, Grace Lai-Hung Wong, Charing Ching-Ning Chong, Po-Hong Liu, Cheuk-Man Chu, Vincent Wai-Sun Wong, Ka-Fai To, Helen L. Reeves, Anthony Wing-Hung Chan
Journal: Liver Cancer (2019)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; The aim of current study was to (1) construct and validate a novel hepatocellular carcinoma (HCC)-specific inflammatory index; (2) compare the performances of the Integrated Liver Inflammatory Score (ILIS) to existing 4 inflammatory indices in HCC; (3) explore the association between the inflammatory indices and systemic/intratumoral inflammatory markers. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Two cohorts from Hong Kong (HK; &lt;i&gt;n&lt;/i&gt; = 1,315) and Newcastle (&lt;i&gt;n&lt;/i&gt; = 574) were studied. A novel index was constructed from the HK training set (&lt;i&gt;n&lt;/i&gt; = 627). The index was constructed from the training set by combing independent prognostic circulating parameters, followed by validating in the validation set of HK cohort (&lt;i&gt;n&lt;/i&gt; = 688) and the Newcastle cohort. Its prognostic performance was compared to 4 inflammatory indices, namely, the neutrophil to lymphocyte ratio, platelet-to-lymphocyte ratio, prognostic nutrition index, and systemic immune-inflammation index, were compared in the HK cohort. Circulating cytokines and intratumoral gene expression were analyzed in a subset of patients with available samples and correlated with the inflammatory indices. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; In the training set of the HK cohort, the ILIS, was generated: –0.057 × albumin (g/L) + 0.978 × log (Bilirubin, µmol/L) + 1.341 × log (alkaline phosphatase, IU/L) + 0.086 × Neutrophil (10&lt;sup&gt;9&lt;/sup&gt;/L) + 0.301 × log (alpha-fetoprotein, µg/L). With cutoff of 2.60 and 3.87, the ILIS could categorize patients into 3 risk groups in the both validation cohorts. ILIS outperforms other inflammatory indices and remains an independent prognosticator for overall survival after adjustment with Barcelona Clinic Liver Cancer (hazard ratio 31.90, &lt;i&gt;p&lt;/i&gt; &amp;#x3c; 0.001). The ILIS had the best prognostic performances as compared to other inflammatory indices. In exploratory analyses, the ILIS correlated with circulating inflammatory cytokines (e.g., IL-8) but not with any intratumoral inflammatory gene expression. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; ILIS is an HCC-specific prognostic index built on 5 readily available blood parameters. Its versatility is validated both Eastern and Western population of HCC. The score is correlated with levels of circulating cytokines.
Response to Sorafenib in FLT3/ITD AML Is Depedent on Co-Occurring Mutational Profile
Authors: Katherine Tarlock, Jessica A. Pollard, Todd A. Alonzo, Robert B. Gerbing, Yi-Cheng Wang, Rhonda E. Ries, Jenny L. Smith, E. Anders Kolb, Alan S Gamis, Richard Aplenc, Soheil Meshinchi
Journal: Blood (2019)
Four-Year Analysis of Murano Study Confirms Sustained Benefit of Time-Limited Venetoclax-Rituximab (VenR) in Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia (CLL)
Authors: John F. Seymour, Thomas J. Kipps, Barbara F. Eichhorst, Peter Hillmen, James D'Rozario, Sarit Assouline, Carolyn Owen, Tadeusz Robak, Javier de la Serna, Ulrich Jaeger, Guillaume Cartron, Marco Montillo, Nicole Lamanna, Su Young Kim, Jenny Wu, Yanwen Jiang, Jue Wang, Marcus Lefebure, Michelle Boyer, Kathryn Humphrey, Arnon P Kater
Journal: Blood (2019)
Abstract 15176: Left Bundle Branch Block and Incident Heart Failure
Authors: Shalini Dixit, Eric Vittinghoff, Elsayed Z Soliman, Susan R Heckbert, Bruce M Psaty, Gregory M Marcus
Journal: Circulation (2018)

Introduction: Left bundle branch block (LBBB) most often occurs in patients with underlying heart disease though it can also be seen in asymptomatic patients with structurally normal hearts. While ...
Rapid Generation of Sustainable HER2-specific T-cell Immunity in Patients with HER2 Breast Cancer using a Degenerate HLA Class II Epitope Vaccine
Authors: Keith L. Knutson, Matthew S. Block, Nadine Norton, Courtney L. Erskine, Timothy J. Hobday, Allan B. Dietz, Douglas Padley, Michael P. Gustafson, Danell Puglisi-Knutson, Toni Kay Mangskau, Saranya Chumsri, Amylou C. Dueck, Lavakumar Karyampudi, Glynn Wilson, Amy C. Degnim
Journal: Clinical Cancer Research (2019)

Patients with HER2+ breast cancer benefit from trastuzumab-containing regimens with improved survival. Adaptive immunity, including cytotoxic T-cell and antibody immunity, is critical to clinical efficacy of trastuzumab. Because Th cells are central to the activation of these antitumor effectors, we reason that HER2 patients treated with trastuzumab may benefit by administering vaccines that are designed to stimulate Th-cell immunity.We developed a degenerate HER2 epitope-based vaccine consisting of four HLA class II-restricted epitopes mixed with GM-CSF that should immunize most (≥84%) patients. The vaccine was tested in a phase I trial. Eligible women had resectable HER2+ breast cancer and had completed standard treatment prior to enrollment and were disease free. Patients were vaccinated monthly for six doses and monitored for safety and immunogenicity.Twenty-two subjects were enrolled and 20 completed all six vaccines. The vaccine was well tolerated. All patients were alive at analysis with a median follow-up of 2.3 years and only two experienced disease recurrence. The percent of patients that responded with augmented T-cell immunity was high for each peptide ranging from 68% to 88%, which led to 90% of the patients generating T cells that recognized naturally processed HER2 antigen. The vaccine also augmented HER2-specific antibody. Immunity was sustained in patients with little sign of diminishing at 2 years following the vaccination.Degenerate HLA-DR-based HER2 vaccines induce sustainable HER2-specific T cells and antibodies. Future studies, could evaluate whether vaccination during adjuvant treatment with trastuzumab-containing regimens improves patient outcomes.
Development of sensitive and specific immunohistochemical assays for pro-apoptotic TRAIL-receptors
Authors: Charlotte M. Roach, Amir Sharifi, Jon Askaa, Rosanne Welcher, Dennis Chenoweth, Clint Lincoln, Svetlana Sosnovtseva, Qinghai Zhao, Ron Johnson, Robin Humphreys, Viktor Roschke, Norma Lynn Fox, Vivian Albert, Wendy Halpern
Journal: Cancer Research (2004)

4957  Targeted induction of apoptosis is an attractive approach for development of novel oncology therapeutics. One method of inducing apoptosis is through the TRAIL-Receptor family, which has five related members only two of which are pro-apoptotic, TRAIL-R1 (DR4) and TRAIL-R2 (DR5). These receptors have a cytoplasmic death-domain and signal to induce the extrinsic cell death pathway; they are also broadly expressed on many human tumors. Agonist antibodies specific for TRAIL-R1 and TRAIL-R2 are in development as potential anti-cancer therapeutics; however, the relationship of receptor expression to response to these agonist antibodies has not been established. To allow for evaluation of this relationship, immunohistochemistry (IHC) assays that detect expression of TRAIL-R1 and TRAIL-R2 in formalin-fixed, paraffin-embedded (FFPE) human tumor tissues were developed. It was critical that these assays detect TRAIL-R1 and TRAIL-R2 with great specificity and a high level of sensitivity, as tumors with low expression may be very significant as an agonist antibody target. Affinity purified rabbit polyclonal antibodies, specific for TRAIL-R1 and TRAIL-R2, were optimized using a two step assay utilizing the EnVision+® visualization system. The optimal antigen retrieval was determined to be heat induced epitope retrieval (HIER). The optimal antibody concentrations were established while employing an incubation time of 30 minutes for the TRAIL-R1 assay and 60 minutes for the TRAIL-R2 assay. The reactions were visualized with 3’3-diaminobenzidine (DAB+). Sections from FFPE pellets from cell lines previously characterized by flow cytometry for surface expression of TRAIL-R1 and TRAIL-R2 demonstrated optimal IHC staining using both assays. Similarly, tumor-enriched xenograft models showed IHC staining with minimal background staining of the surrounding non-reactive mouse tissue. Optimal staining for both TRAIL-R1 and TRAIL-R2 was observed on a wide range of human tumor specimens, including colon, lung and breast carcinoma. Staining of the tumor cells was favorable with minimal background staining in the stroma. In conclusion, sensitive and specific IHC assays have been developed for demonstration of TRAIL-R1 and TRAIL-R2 expression for use on FFPE human tumor samples. These assays allow for distinguishing between expression of TRAIL-R1 and TRAIL-R2, and are suitable for the further exploration of the relationship between TRAIL-R1 and TRAIL-R2 expression and therapeutic response to agonist antibodies.
A methodological approach to investigating a nationwide clinical specimen contamination problem in England
Authors: L Pezzoli, C Campbell, T  L Lamagni, E Johnson, A Saei, G Duckworth
Journal: Eurosurveillance (2009)

Outbreaks of pseudo-infection due to contamination of specimens have been described, often as localised incidents. From August 2006, several English hospital laboratories began to refer an unusually high number of isolates of the fungus Paecilomyces variotii from clinical specimens to the national mycology reference laboratory for microbiological testing. We describe the methods used during the outbreak investigation in order to provide infection control specialists with an overview of how such national incidents may be investigated. We surveyed the hospitals reporting the contamination problem and conducted microbiological and environmental sampling. We applied analytical epidemiology to supply chain data, comparing the supply lines of key equipment to affected and unaffected hospitals in England. The survey was useful to describe procedures and equipment in use in the hospitals reporting the problem. The microbiological aspects of the investigation helped us understand how the fungal spores were distributed in the hospital environment. In the supply chain investigation we used data that was previously only used for logistical purposes. Overall the investigation were methodologically challenging, with no existing protocol to guide the investigators. To our knowledge, this is a novel approach to the investigation of such a widespread contamination problem, affecting geographically disparate hospitals at the same time.
RNA Splicing Defects in Cancer-Linked Genes Indicate Mutation or Focal Gene Deletion and Are Associated with TKI Resistance in CML
Authors: Naranie Shanmuganathan, Daniel Thomson, Carol Wadham, Verity A Saunders, Nur Hezrin Shahrin, David T Yeung, Hamish S Scott, Timothy P. Hughes, Andreas Schreiber, Susan Branford
Journal: Blood (2019)
Carboplatin versus cisplatin-based adjuvant chemotherapy in elderly patients with stages IB, II, and IIIA non-small cell lung cancer in the community setting.
Authors: Fei Gu, Juan P. Wisnivesky, Grace Mhango, Gary M. Strauss
Journal: Journal of Clinical Oncology (2013)

7533 Background: It remains controversial whether completely resected elderly NSCLC patients should receive adjuvant chemotherapy (ACT) and with what treatment regimen. We previously reported from a SEER-Medicare analysis of cases diagnosed up to 2005, that carbo-ACT is given much more frequently than cis-ACT and both are associated with improved overall survival (OS). Since randomized ACT trials were published around 2005, an update is necessary to reflect more recent practice patterns. Methods: We identified 16,420 patients &gt;65 years in the SEER-Medicare database with resected stage IB-IIIA NSCLC, diagnosed between 1992 and 2007. Among these patients, 1,803 (11%) received platinum-ACT. Propensity score methods and Cox regression analyses were used to assess survival outcomes, as well as to compare carbo- versus cis-based therapy, while controlling for potential confounders. Results: Among those receiving platinum-based ACT, of whom 83% received carbo, there was a significant OS survival advantage compared to those receiving no ACT (TABLE). Carbo-ACT is associated with similar OS as compared to cis-ACT. The carbo/paclitaxel doublet was the most commonly used regimen, given to 52%. Chemotherapy-related toxicities requiring hospitalization were comparable between carbo- and cis-ACT groups, except for significantly less dehydration and anemia among those receiving carbo-ACT. Conclusions: In community practice reflected in this SEER-Medicare study, a minority of completely resected stage IB-IIIA NSCLC received platinum-based ACT that is associated with improved OS. Carbo-ACT was given in a 5:1 ratio compared to cis-ACT, had comparable OS advantage, and a somewhat more favorable toxicity profile. [Table: see text]
Reproducibility of MALDI-TOF mass spectrometry measurements on complex biofluids.
Authors: L. Dekker, J. Dalebout, G. Jenster, I. Siccama, P. Sillevis Smitt, T. Luider
Journal: Cancer Research (2004)

3544  MALDI-TOF (Matrix-Assisted Laser Desorption Ionization Time Of Flight) is characterized by excellent mass accuracy. In contrast, the reproducibility of relative intensities is low in matrix assisted Laser Desorption Ionization Time of Flight (MALDI-TOF) and SELDI-TOF MS. This is caused by ion suppression, amount of matrix, combined crystallization of the matrix and the analyte. Crystallization depends on a number of factors: the peptide content of the sample, contamination in the analyte and the ratio of matrix and analyte. In this study we determined the reproducibility and quantification of tryptic peptides from cerebrospinal proteins by mass spectrometry. Serial dilutions of two cerebrospinal fluid (CSF) samples were digested with trypsin in a detergent solution (Rapigest, Massachusetts, USA). Subsequently the samples were purified over a C18 zip-plate (Millipore, Billerica, USA). The purified tryptic digests were spotted on a MALDI target plate and measured automatically in a MALDI-TOF MS (Biflex III, Bruker Daltonics, Germany). Each sample was digested and measured 36 times. All the spectra were analyzed, subsequently aligned and calibrated using omnipresent albumin peptide peaks. Peak detection was performed with a signal to noise ratio of 2 on the calibrated spectra. Peak positions in 36 spectra were grouped with a clustering algorithm and the peak heights were normalized. The coefficient of variance (CV) was determined as a measure of reproducibility. Over 200 peptide peaks were present in one spectrum and 120 clusters of these peaks could be identified as mono-isotopic peptides. The average mass accuracy of the peaks in these spectra was 25 ppm with a CV of 0.003%. Sixty clusters of mono isotopic peptide peaks were present in 50% of the spectra. The average CV of the intensity of the 60 mono-isotopic peaks was 37% (range 4%–134%). The accuracy and reproducibility of mass determination with this method are excellent. However, intensity measurements of peaks are much less reproducible indicating that MALDI-TOF and SELDI-TOF analyses can only be used in a semi-quantitative manner. CV9s mentioned in mass spectrometry are highly linked to the method used for peak detection and are thus quite subjective.
A Phase I/II Study of Lenalidomide Plus Obinutuzumab in Relapsed Indolent Lymphoma
Authors: Nathan H Fowler, Loretta J. Nastoupil, Collin Chin, Paolo Strati, Fredrick B. Hagemeister, Luis E. Fayad, Jason R. Westin, Sheryl G Forbes, Janine Arafat, Lei Feng, Ranjit Nair, Raphael E Steiner, Felipe Samaniego, Sattva S Neelapu
Journal: Blood (2019)