tbuckley/cabot-search huggingface dataset:
Incorporating Physical Function and Cognition Into Mortality Risk Assessment for Acute Myeloid Leukemia
Authors: Kah Poh Loh, Heidi Klepin
Journal: JAMA Oncology (2018)

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Up-regulation of Hsp27 in prostate cancer cell lines induces resistance to various chemotherapeutics through Bax interaction
Authors: Romina Wiedmann, Amina Zoubeidi, Marc Germain, Eliana Beraldi, Martin Gleave
Journal: Cancer Research (2008)

2911    Introduction:  Heat shock protein 27 (Hsp27) is a cytoprotective chaperone which is highly overexpressed in several human cancers such as prostate and breast. Suppression of Hsp27 expression has been shown to render human cancer cells sensitive to chemotherapeutic drug-mediated apoptosis and an antisense oligonucleotide against Hsp27 (OGX-427, OncoGenex, Vancouver, BC) is currently being evaluated in a phase I clinical trial against solid tumors. However, the mechanisms by which this multifunctional protein confers drug-resistance remain incompletely defined. Since Hsp27 inhibits intrinsic pathway activation, we hypothesize that Hsp27 could regulate drug-induced cell death by sequestering the pro-apoptotic protein Bax (Bcl-2 family) and thereby protecting cells from apoptosis.   Methods:  Hsp27 overexpressing or parental LNCaP cells transfected with either siRNAHsp27 or OGX-427 were treated with various stressors including MG132 (Proteosome Inhibitor), 17-AAG (Hsp90-Inhibitor) or Paclitaxel (cytotoxic agent). Cellular responses were assessed by the following methods: MTS-Assay, Flow-cytometry, Western Blot, Immunoprecipitation, Immunoflourescence and Fractionation.   Results:  Forced overexpression of Hsp27 increased prostate cancer cell resistance to chemotherapeutics, whereas down-regulation by siRNA or OGX-427 induced sensitivity to chemotherapeutics and enhanced apoptosis. Moreover, overexpression of Hsp27 inhibited drug-induced Bax conformational change by forming a complex with Bax. Through its interaction with Bax, Hsp27 kept Bax in the cytoplasm, thereby protecting cells from apoptosis. In contrast, Hsp27 knockdown led to Bax conformational changes resulting in the exposure of an amino-terminal epitope of Bax, translocation to the mitochondria and increased apoptosis.   Conclusion:  Taken together, this data suggests that elevated Hsp27 expression levels confer resistance to various classes of anticancer agents by interfering with Bax apoptotic activity. This provides further evidence that abrogation of Hsp27 can be used as a strategy to increase the efficacy of different chemotherapeutics in prostate cancer.
Multifunctional degradable electronic scaffolds for cardiac tissue engineering
Authors: Ron Feiner, Sharon Fleischer, Assaf Shapira, Or Kalish, Tal Dvir
Journal: Journal of Controlled Release (2018)

The capability to on-line sense tissue function, provide stimulation to control contractility and efficiently release drugs within an engineered tissue microenvironment may enhance tissue assembly and improve the therapeutic outcome of implanted engineered tissues. To endow cardiac patches with such capabilities we developed elastic, biodegradable, electronic scaffolds. The scaffolds were composed of electrospun albumin fibers that served as both a substrate and a passivation layer for evaporated gold electrodes. Cardiomyocytes seeded onto the electronic scaffolds organized into a functional cardiac tissue and their function was recorded on-line. Furthermore, the electronic scaffolds enabled to actuate the engineered tissue to control its function and trigger the release of drugs. Post implantation, these electronic scaffolds degraded, leading to the dissociation of the inorganic material from within the scaffold. Such technology can be built upon to create a variety of degradable devices for tissue engineering of various tissues, as well as pristine cell-free devices with electronic components for short-term in vivo use.
Epigenomes in Cardiovascular Disease
Authors: Manuel Rosa-Garrido, Douglas J. Chapski, Thomas M. Vondriska
Journal: Circulation Research (2018)

If unifying principles could be revealed for how the same genome encodes different eukaryotic cells and for how genetic variability and environmental input are integrated to impact cardiovascular health, grand challenges in basic cell biology and translational medicine may succumb to experimental dissection. A rich body of work in model systems has implicated chromatin-modifying enzymes, DNA methylation, noncoding RNAs, and other transcriptome-shaping factors in adult health and in the development, progression, and mitigation of cardiovascular disease. Meanwhile, deployment of epigenomic tools, powered by next-generation sequencing technologies in cardiovascular models and human populations, has enabled description of epigenomic landscapes underpinning cellular function in the cardiovascular system. This essay aims to unpack the conceptual framework in which epigenomes are studied and to stimulate discussion on how principles of chromatin function may inform investigations of cardiovascular disease and the development of new therapies.
Abstract 11510: Missed Opportunities in Use of Medical Emergency Teams Prior to In-Hospital Cardiac Arrest
Authors: Maya L Chan, Fengming Tang, Paul S Chan
Journal: Circulation (2015)

Background: Hospitals often employ Medical Emergency Teams (MET) to respond to patients with acute physiological decline to prevent in-hospital cardiac arrest (IHCA). However, it is unknown how often patients fail to have a MET evaluation preceding IHCA, and whether these patients have severe vital sign abnormalities suggesting missed opportunities for MET activation. Methods: Within Get With The Guidelines-Resuscitation, we identified 29,956 patients with IHCA on general inpatient or telemetry floors from 240 hospitals that submitted data on both IHCA and MET evaluations. We determined the proportion without MET evaluation before IHCA. Among those without MET evaluation, we examined the frequency of vital sign abnormalities 1, 2, and 4 hours before IHCA. We used stringent definitions for the following six vital sign abnormalities: heart rate &gt;150 or &lt;30 beats per minute, respiratory rate &gt;35 or &lt;8 breaths per minute, systolic blood pressure &lt;80 mm Hg, and oxygen saturation level of &lt;80%. Results: Overall, the vast majority (24,733 [82.6%]) of patients with IHCA did not have a preceding MET evaluation. Vital sign data were available for 18,064 patients without MET evaluation. Of these patients, 7109 (39.4%), 5536 (30.6%), and 2368 (13.1%) had at least one severe vital sign abnormality ≥ 1, 2, and 4 hours before IHCA, respectively (TABLE). Furthermore, 13.7% had a Modified Early Warning Score (MEWS) ≥ 4 at least 1 hour before IHCA. Conclusion: Although MET teams are designed to prevent IHCA, many patients with severe vital sign abnormalities prior to IHCA did not have a MET evaluation. These findings suggest missed opportunities to use MET teams efficiently in hospitals.
<i>BRCA1/2</i> Mutations and Bevacizumab in the Neoadjuvant Treatment of Breast Cancer: Response and Prognosis Results in Patients With Triple-Negative Breast Cancer From the GeparQuinto Study
Authors: Peter A. Fasching, Sibylle Loibl, Chunling Hu, Steven N. Hart, Hermela Shimelis, Raymond Moore, Christian Schem, Hans Tesch, Michael Untch, Jörn Hilfrich, Mahdi Rezai, Bernd Gerber, Serban Dan Costa, Jens-Uwe Blohmer, Tanja Fehm, Jens Huober, Cornelia Liedtke, Richard M. Weinshilboum, Liewei Wang, James N. Ingle, Volkmar Müller, Valentina Nekljudova, Karsten E. Weber, Brigitte Rack, Matthias Rübner, Gunter von Minckwitz, Fergus J. Couch
Journal: Journal of Clinical Oncology (2018)

Purpose BRCA1/2 mutations are frequent in patients with triple-negative breast cancer (TNBC). These patients are often treated with primary systemic chemotherapy. The aim of this study was to analyze the effects of BRCA1/2 mutations on pathologic complete response (pCR) and disease-free survival (DFS) in a cohort of patients with TNBC treated with anthracycline and taxane–containing chemotherapy, with or without bevacizumab. Patients and Methods Germline DNA was sequenced to identify mutations in BRCA1 and BRCA2 in 493 patients with TNBC from the GeparQuinto study. The pCR rates were compared in patients with and without mutation, as well as in patients treated with and without bevacizumab. In addition, the influence of BRCA1/2 mutation status and pCR status on DFS was evaluated relative to treatment. Results BRCA1/2 mutations were detected in 18.3% of patients with TNBC. Overall, patients with mutations had a pCR rate of 50%, compared with 31.5% in patients without a mutation (odds ratio [OR], 2.17; 95% CI, 1.37 to 3.46; P = .001). The pCR rate among patients treated with bevacizumab was 61.5% for BRCA1/2 mutation carriers and 35.6% for those without mutations (OR, 2.90; 95% CI, 1.43 to 5.89; P = .004). pCR was a strong predictor of DFS for patients without BRCA1/2 mutations (hazard ratio, 0.18; 95% CI, 0.11 to 0.31) but not for patients with BRCA1/2 mutations (hazard ratio, 0.74; 95% CI, 0.32 to 1.69). Conclusion The addition of bevacizumab may increase the pCR after standard neoadjuvant chemotherapy for patients with TNBC with BRCA1/2 mutations. In patients treated with anthracycline and taxane–based chemotherapy (with or without bevacizumab), pCR was a weaker predictor of DFS for BRCA1/2 mutation carriers than for patients without mutations.
FACE-Q Skin Cancer Module for measuring patient-reported outcomes following facial skin cancer surgery
Authors: E.H. Lee, A.F. Klassen, S.J. Cano, K.S. Nehal, A.L. Pusic
Journal: British Journal of Dermatology (2018)

The patient's perspective of their facial scar after skin cancer surgery influences perception of care and quality of life (QoL). Appearance satisfaction after surgery is also an important but often overlooked treatment outcome.To report the psychometric validation of the FACE-Q Skin Cancer Module consisting of five scales, measuring appearance satisfaction (Satisfaction with Facial Appearance, Appraisal of Scars), QoL (Cancer Worry, Appearance-related Psychosocial Distress) and the patient experience (Satisfaction with Information: Appearance).Participants underwent Mohs surgery for facial basal or squamous cell carcinoma or excision of early facial melanoma. Cohort 1 received a set of scales before and after surgery. Cohort 2 received the scales on two occasions in the postoperative period for test-retest reliability. Rasch measurement theory was used to select (item-reduce) the most clinically meaningful items for the scales. Reliability, validity, floor and ceiling effects and responsiveness were also analysed.Of 334 patients, 209 (response rate 62·6%) were included. Rasch analysis reduced the total scale items from 77 to 41. All items had ordered thresholds and good psychometric fit. Reliability was high (Person separation index and Cronbach's α ≥ 0·90) and scales measuring similar constructs were correlated. High floor and ceiling effects were seen for the scales. The Cancer Worry scale demonstrated responsiveness (P = 0·004).The FACE-Q Skin Cancer Module meet the requirements of the Rasch model providing linearized measurement. Discriminating between patients with minimal appearance or worry impairment may be a limitation. The scales can be used for larger validation studies, clinical practice and research.
Cellular Origin and Functional Relevance of Collagen I Production in the Kidney
Authors: Simone Buchtler, Alexandra Grill, Stefanie Hofmarksrichter, Petra Stöckert, Gabriela Schiechl-Brachner, Manuel Rodriguez Gomez, Sophia Neumayer, Kathrin Schmidbauer, Yvonne Talke, Barbara M. Klinkhammer, Peter Boor, Alexander Medvinsky, Kerstin Renner, Hayo Castrop, Matthias Mack
Journal: Journal of the American Society of Nephrology (2018)

Background Interstitial fibrosis is associated with chronic renal failure. In addition to fibroblasts, bone marrow-derived cells and tubular epithelial cells have the capacity to produce collagen. However, the amount of collagen produced by each of these cell types and the relevance of fibrosis to renal function are unclear.Methods We generated conditional cell type-specific collagen I knockout mice and used (reversible) unilateral ureteral obstruction and adenine-induced nephropathy to study renal fibrosis and function.Results In these mouse models, hematopoietic, bone marrow-derived cells contributed to 38%-50% of the overall deposition of collagen I in the kidney. The influence of fibrosis on renal function was dependent on the type of damage. In unilateral ureteral obstruction, collagen production by resident fibroblasts was essential to preserve renal function, whereas in the chronic model of adenine-induced nephropathy, collagen production was detrimental to renal function.Conclusions Our data show that hematopoietic cells are a major source of collagen and that antifibrotic therapies need to be carefully considered depending on the type of disease and the underlying cause of fibrosis.
Early Intravascular Events Are Associated with Development of Acute Respiratory Distress Syndrome. A Substudy of the LIPS-A Clinical Trial
Authors: Raja-Elie E. Abdulnour, Tina Gunderson, Ioanna Barkas, Jack Y. Timmons, Cindy Barnig, Michelle Gong, Daryl J. Kor, Ognjen Gajic, Daniel Talmor, Rickey E. Carter, Bruce D. Levy
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Acute respiratory distress syndrome (ARDS) is a devastating illness with limited therapeutic options. A better understanding of early biochemical and immunological events in ARDS could inform the development of new preventive and treatment strategies.
Autoimmune Th17 Cells Induced Synovial Stromal and Innate Lymphoid Cell Secretion of the Cytokine GM-CSF to Initiate and Augment Autoimmune Arthritis
Authors: Keiji Hirota, Motomu Hashimoto, Yoshinaga Ito, Mayumi Matsuura, Hiromu Ito, Masao Tanaka, Hitomi Watanabe, Gen Kondoh, Atsushi Tanaka, Keiko Yasuda, Manfred Kopf, Alexandre J. Potocnik, Brigitta Stockinger, Noriko Sakaguchi, Shimon Sakaguchi
Journal: Immunity (2018)
HIV vaccine candidate activation of hypoxia and the inflammasome in CD14+ monocytes is associated with a decreased risk of SIVmac251 acquisition
Authors: Monica Vaccari, Slim Fourati, Shari N. Gordon, Dallas R. Brown, Massimilano Bissa, Luca Schifanella, Isabela Silva de Castro, Melvin N. Doster, Veronica Galli, Maria Omsland, Dai Fujikawa, Giacomo Gorini, Namal P. M. Liyanage, Hung V. Trinh, Katherine M. McKinnon, Kathryn E. Foulds, Brandon F. Keele, Mario Roederer, Richard A. Koup, Xiaoying Shen, Georgia D. Tomaras, Marcus P. Wong, Karissa J. Munoz, Johannes S. Gach, Donald N. Forthal, David C. Montefiori, David J. Venzon, Barbara K. Felber, Margherita Rosati, George N. Pavlakis, Mangala Rao, Rafick-Pierre Sekaly, Genoveffa Franchini
Journal: Nature Medicine (2018)
Targeting skeletal endothelium to ameliorate bone loss
Authors: Ren Xu, Alisha Yallowitz, An Qin, Zhuhao Wu, Dong Yeon Shin, Jung-Min Kim, Shawon Debnath, Gang Ji, Mathias P. Bostrom, Xu Yang, Chao Zhang, Han Dong, Pouneh Kermani, Sarfaraz Lalani, Na Li, Yifang Liu, Michael G. Poulos, Amanda Wach, Yi Zhang, Kazuki Inoue, Annarita Di Lorenzo, Baohong Zhao, Jason M. Butler, Jae-Hyuck Shim, Laurie H. Glimcher, Matthew B. Greenblatt
Journal: Nature Medicine (2018)
Reply to García-Cano et al.
Authors: A. Dormann
Journal: Endoscopy (2005)

I read with interest Dr. García-Cano’s remarks concerning our recently published paper on the use of self-expandable plastic stents (SEPS) in malignant strictures [1]. The main advantage of using SEPS in esophageal carcinoma is the absence of metal meshes and the complete coverage of the stent by a silicone membrane, which reduces benign tissue hyperplasia and allows safe removal of the device even after extended periods.
Quality and Safety in Health Care, Part XLI
Authors: Jay A. Harolds
Journal: Clinical Nuclear Medicine (2018)

Abstract The IMPACT Registry is a repository of information for heart catheterizations for congenital heart disease regardless of age and also the catheterizations for acquired heart disease in children. The registry collects information on outcomes, provides quality improvement opportunities for participants, provides reports to participants comparing their results with national results, compares the volume of catheter work done at an institution with the frequency of adverse events, and provides information that may be helpful in evaluating the use of medical devices and treatment options.
ALBI-RT: A novel radiation therapy specific hepatotoxicity prediction model for hepatocellular carcinoma patients.
Authors: Stephanie K Schaub, Stephen R. Bowen, Tobias Robert Chapman, Matthew J. Nyflot, Smith Apisarnthanarax
Journal: Journal of Clinical Oncology (2018)

444 Background: The albumin-bilirubin (ALBI) grade system was optimized to predict survival in hepatocellular carcinoma (HCC) patients; however, its applicability to patients treated with radiation therapy (RT) is unclear. We propose a novel analysis of the ALBI equation, designated ALBI-RT, to assess hepatotoxicity risk after RT. Methods: We retrospectively reviewed 48 consecutive HCC patients treated with RT (2013-2016). Raw ALBI values and Child-Pugh (CP) scores were calculated. Any patient deaths were examined for radiation induced liver disease (RILD). Raw ALBI was assessed as a continuous variable to perform ROC analyses to identify cutoffs for overall survival (OS) and RILD-specific survival (RILD-SS). Univariate predictors of OS and RILD-SS were evaluated using Cox regression to determine hazard ratios (HR). Results: Patient cohort was comprised of 60% CP-A and 39% CP-B/C. Median follow-up and OS was 13 and 10 months, respectively. There were 18 deaths with 6 ascribed to RILD. We identified a raw ALBI cutoff at -1.70 (AUC = 0.94, p = 0.008) that was predictive of RILD-SS with a sensitivity of 100% and specificity of 71%. Dichotimization of RILD-SS cutoff generated two ALBI-RT risk categories: low-risk A &lt; -1.70 (n = 29) and high-risk B ≥ -1.70 (n = 18). ALBI-RT subdivided CP-A patients, identifying 14% at increased risk of RILD; conversely, ALBI-RT grade A identified 21% of CP-B/C patients at a decreased risk of RILD. For OS, raw ALBI as a continuous variable (HR 3.0, p = 0.02), and to a lesser degree ALBI-RT Grade B (HR 2.4, p = 0.06), performed similarly to traditional ALBI grade (HR 3.0, p = 0.01), and CP score (HR 1.4, p = 0.03). In contrast for RILD-SS, raw ALBI as a continuous variable (HR 25.1, p = 0.01) and ALBI-RT Grade B (HR 9.9, p = 0.04) were associated with an elevated relative risk of RILD than traditional ALBI grade (HR 5.8, p = 0.02) and CP score (HR 2.3, p = 0.003). Conclusions: ALBI-RT is a promising metric for pre-treatment assessment of HCC patients for predicting RILD-related death after RT with an elevated relative-risk compared to both CP and conventional ALBI grades. Future prospective evaluation and validation in independent data sets will strengthen the generalizability and utility of ALBI-RT.
Targeted reversal and phosphorescence lifetime imaging of cancer cell metabolism via a theranostic rhenium(I)-DCA conjugate
Authors: Jing Yang, Qian Cao, Hang Zhang, Liang Hao, Danxia Zhou, Zhenji Gan, Zhiwei Li, Ye-Xiang Tong, Liang-Nian Ji, Zong-Wan Mao
Journal: Biomaterials (2018)
Plaque Morphology as Predictor of Late Plaque Events in Patients With Asymptomatic Type 2 Diabetes
Authors: David A Halon, Idit Lavi, Ofra Barnett-Griness, Ronen Rubinshtein, Barak Zafrir, Mali Azencot, Basil S Lewis
Journal: JACC. Cardiovascular imaging (2018)
Clinical outcomes of gemcitabine plus nab-paclitaxel (GnP) in initially diagnosed locally advanced pancreatic cancer.
Authors: Yusuke Hashimoto, Hideaki Takahashi, Izumi Ohno, Hiroshi Imaoka, Mitsuhito Sasaki, Kumiko Umemoto, Kazuo Watanabe, Gen Kimura, Shuichi Mitsunaga, Masafumi Ikeda
Journal: Journal of Clinical Oncology (2018)

407 Background: Gemcitabine plus nab-Paclitaxel has shown improved survival in patients with metastatic pancreatic cancer in MPACT. Many studies have been investigating the survival benefit of GnP in LACP patients. The aim of this study is to clinical outcome of GnP in initially diagnosed LAPC in our single tertiary institution. Methods: LACP patients who received GnP as initial chemotherapy were identified between December 2014. and December 2016 from our database retrospectively. Demographic characteristics, disease status, response, conversion to resection and survival was reviewed. Resectability was determined at our hepatobiliary pancreatic tumor board, reflecting Japanese guideline of pancreatic cancer. Results: We identified 55 LACP patients initially treated with GnP (median age: 67 year old, female was 49%, ECOG PS 0/1, 62%/38%, pancreatic head 58%, baseline tumor size: median 32mm (18-62), CA19-9: median 139ng/ml (3.9-12956)). Best objective response rate was 58% and median time to partial response was 60 days (40-212). Median overall survival (mOS) was 24.7 months (95%CI :15.5-not reached). Nine patients (16%:9/55) were re-evaluated as resectable with CT and normalized CA19-9/CEA and subsequently proceeded to conversion to resection. Seven patients (13%:7/55) achieved R0 resection and sequentially performed adjuvant six- month duration of GnP. Median time to resection from initial GnP administration was 5.2 months (4.0-7.3). LAPC patients who achieved conversion to resection was associated with better overall survival than non-resected LAPC in log-rank test (mOS: all alive :12.1-25.4months vs 21.5 months 95%Cl:15.5-, HR:0.493 range: NA, P = 0.043). Shrinking tumor minimal size from the baseline was the factor to successful conversion in univariate analysis (P = 0.006). Conclusions: GnP showed promising results of response and overall survival in uLAPC patients. Conversion to resection in carefully selected uLAPC currently suggests an early surgical benefit, but longer follow-up and more cases will be required to assess the potential long-term benefit of conversion therapy.