tbuckley/cabot-search huggingface dataset:
A murder mystery in the liver: who done it and how?
Authors: Lily Dara, Zhang-Xu Liu, Neil Kaplowitz
Journal: Journal of Clinical Investigation (2016)

Hepatocyte death, which can be apoptosis or necrosis depending on the context, is a prominent feature of liver disease. The lectin concanavalin A (ConA) activates immune cells, resulting in inflammatory liver injury and hepatocyte necrosis. In this issue of the JCI, Günther et al. demonstrate that the pseudokinase mixed lineage kinase domain-like protein (MLKL) participates in hepatocyte death in ConA injury and that MLKL-mediated death is independent of the receptor-interacting protein kinase RIPK3. RIPK3 was absent in hepatocytes, and MLKL-deficient mice, but not RIPK3-deficient mice, were protected from ConA-induced liver injury. The authors also present evidence that an unidentified kinase activates MLKL, as RIPK1 bound MLKL but did not phosphorylate it. Moreover, ConA rapidly induced MLKL, mediated by the IFN-γ/STAT1 pathway, while activation and translocation to the plasma membrane required TNF. Increased phospho-MLKL staining in liver biopsies from patients with autoimmune hepatitis suggests a role for MLKL in this disease. This study describes a previously unrecognized form of cell death in the liver that should be further explored as a potential therapeutic target in immune-mediated liver injury.
Sequential administration of new agents (NAs) after docetaxel (DOC) in metastatic castration-resistant prostate cancer (mCRPC) patients (pts): Impact of disease control (DC) duration in second line on the subsequent line outcomes.
Authors: Francesca Maines, Ugo De Giorgi, Gaetano Facchini, Lucia Fratino, Donatello Gasparro, Daniele Alesini, Umberto Basso, Marcello Tucci, Cinzia Ortega, Sarah Scagliarini, Francesco Verderame, Sandro Barni, Alessandro D'Angelo, Giovanni Vicario, Maddalena Donini, Francesco Carrozza, Teodoro Sava, Zuzana Sirotova, Daniele Santini, Orazio Caffo
Journal: Journal of Clinical Oncology (2016)

210 Background: Abiraterone acetate (AA), cabazitaxel (CABA), and enzalutamide (ENZ) are NAs which demonstrated their efficacy in mCRPC pts who have previously treated with DOC. Unfortunately all pts develop a resistance to these drugs and eventually show a progression of disease. Since the androgen receptor machinery remains the ultimate target of NAs in mCRPC post-DOC, some mechanisms of resistance could be common to all NAs. To date, NAs are sequentially administered in the hope of obtaining a cumulative survival benefit. To date it is unknown if the DC duration influence the outcomes of the subsequent treatments. The present study was aimed to retrospectively assess this issue in a large series of mCRPC pts. Methods: We recorded the clinical outcomes of all treatments received after DOC. For the study purpose, we categorized the pts according to the duration of DC (absence of progression) during NA-based second line: DC ≤ 3 mos (primary resistance – PRe); DC from 3.1 to 11.9 mos (intermediate sensitivity – IS); DC ≥ 12 mos (long term disease control – LTDC). Results: A consecutive series of 291 mCRPC pts, median age 71 yrs (46-91), with bone (88%), nodal (53%) or visceral (18%) mets, was collected. All pts received a NA-based as second line after DOC: 160 (55%) received AA, 99 (33%) CABA and 32 (11%) ENZ. PRe was observed in 56 pts (23 AA – 25 CABA – 8 ENZ), IS in 178 (101 AA – 58 CABA – 19 ENZ), LTDC in 57 (36 AA – 16 CABA – 5 ENZ). The third-line clinical outcomes are detailed in the table. Conclusions: From this data, it appears that DC duration may be a prognostic factor, as a probable result of pts/disease selection. In fact, pts progressing more than 12 mos from the start of NA-based second line appear to have more probabilities to live longer, compared to pts progressing earlier, when they receive another NA-based third line therapy. [Table: see text]
Rethinking economics of misplaced priorities within the Hellenic opportunistic cancer screening policy
Authors: D. Mauri, K. Kamposioras, I. Cortinovis, V. Karampoiki, E. Thanopoulou, G. Koukourakis, D. Tzachanis, G. Zacharias, D. Pectasides, G. Casazza
Journal: Journal of Clinical Oncology (2008)

17521 Background: Screening is a significant method for cancer control. Nevertheless a high implementation of non cost effective tests constitutes a major health economics burden. Purpose of the study was to perform a cost analysis in order 1) to estimate the expenses used for evidence-based (EB), non-EB and undefined evidence (UE) screening tests among a large sample of Hellenic individuals and 2) to assess potential benefit of a correct redistribution of resources in screening performance. Methods: A questionnaire based cross sectional survey was conducted in Greece. 7,012 individuals entered the study. Annual cumulative costs were calculated for screening tests in the following settings EB, non EB and UE, according with current European Code against Cancer guidelines. Among males: EB tests = fecal occult blood test (FOBT); Non-EB tests = chest x-ray, urine and transrectal ultrasound; UE tests = full blood count (FBC) and PSA. Among female: EB tests = Pap test (PAP), mammography (MRX), FOBT. Non-EB tests = chest X-ray, urine test, breast ultrasound (USB); UE tests = FBC. Since we considered 80% population coverage with EB tests as optimal standard, we calculate the annual baseline costs for an EB maximal screening benefit (EBmax). Results: Among males the cumulative costs spent per EB was 1% of EBmax while the redistribution of the actuarial expenses of non-EB and UE provide 107% coverage of EBmax. For females the actual coverage represents the 29.1% of EBmax. When both non-EB and UE tests are considered further 17.4% of EBmax is provided accounting altogether to 46.5% of EBmax. Summing up the money saved from male EBmax screening a total 52.7% of female EBmax is still covered. Conclusions: Actuarial opportunistic screening is expensive and not satisfactory. Our cost analysis indicates that a rationale redistribution of actuarial spending could provide the health system the EBmax coverage among male and a notable part of resources needed for EBmax among female. Thereafter a national EBmax screening implementation seems economically feasible. No significant financial relationships to disclose.
Single Cell Network Profiling (SCNP) Functionally Characterizes FLT3 Pathway Deregulation in Non-M3 Acute Myeloid Leukemia (AML) and Provides Prognostic Value Independent From Mutational Status
Authors: Alessandra Cesano, Santosh Putta, Kavita Mathi, David B. Rosen, Urte Gayko, Rachael E. Hawtin, Larry D Cripe, Zhuoxin Sun, Martin S. Tallman, Elisabeth Paietta
Journal: Blood (2011)
Association of Selective Serotonin Reuptake Inhibitor Exposure During Pregnancy With Speech, Scholastic, and Motor Disorders in Offspring
Authors: Alan S. Brown, David Gyllenberg, Heli Malm, Ian W. McKeague, Susanna Hinkka-Yli-Salomäki, Miia Artama, Mika Gissler, Keely Cheslack-Postava, Myrna M. Weissman, Jay A. Gingrich, Andre Sourander
Journal: JAMA Psychiatry (2016)

Speech/language, scholastic, and motor disorders are common in children. It is unknown whether exposure to selective serotonin reuptake inhibitors (SSRIs) during pregnancy influences susceptibility to these disorders.To examine whether SSRI exposure during pregnancy is associated with speech/language, scholastic, and motor disorders in offspring up to early adolescence.This prospective birth cohort study examined national population-based register data in Finland from 1996 to 2010. The sampling frame includes 845 345 pregnant women and their singleton offspring with data on maternal use of antidepressants and depression-related psychiatric disorders during pregnancy.There were 3 groups of offspring: 15 596 were in the SSRI-exposed group, ie, had mothers diagnosed as having depression-related psychiatric disorders with a history of purchasing SSRIs during pregnancy; 9537 were in the unmedicated group, ie, had mothers diagnosed as having depression-related psychiatric disorders without a history of purchasing SSRIs during pregnancy; and 31 207 were in the unexposed group, ie, had mothers without a psychiatric diagnosis or a history of purchasing SSRIs.Cumulative incidence of speech/language, scholastic, or motor disorders (829, 187, and 285 instances, respectively) from birth to 14 years. All hypotheses tested were formulated before data collection.Of the 56 340 infants included in the final cohort, 28 684 (50.9%) were male and 48 782 (86.6%) were 9 years or younger. The mean (SD) ages of children at diagnosis were 4.43 (1.67), 3.55 (2.67), and 7.73 (2.38) for speech/language, scholastic, and motor disorders, respectively. Offspring of mothers who purchased SSRIs at least twice during pregnancy had a significant 37% increased risk of speech/language disorders compared with offspring in the unmedicated group. The cumulative hazard of speech/language disorders was 0.0087 in the SSRI-exposed group vs 0.0061 in the unmedicated group (hazard ratio, 1.37; 95% CI, 1.11-1.70; P = .004). There was a significantly increased risk of these disorders in offspring in the SSRI-exposed and unmedicated groups compared with offspring in the unexposed group. For scholastic and motor disorders, there were no differences between offspring in the SSRI-exposed group and in the unmedicated group.Exposure to SSRIs during pregnancy was associated with an increased risk of speech/language disorders. This finding may have implications for understanding associations between SSRIs and child development.
FCGR3A V/F 158 Polymorphism Is Not Associated with Response to Rituximab in adult's Immune Thrombocytopenia
Authors: Constance Guillaud Danis, France Noizat-Pirenne, Christophe Tournamille, Olivier Fain, Jean-François Viallard, Bertrand Godeau, Marc Michel
Journal: Blood (2012)
Bortezomib-Doxorubicin-Dexamethasone (BDD) in Patients with Acute Light Chain Induced Renal Failure (ARF) in Multiple Myeloma (MM). Final Results of a Phase II Study.
Authors: Heinz Ludwig, Zdenek Adam, Roman Hajek, Richard Greil, Elena Tóthová, Felix Keil, Eva-Maria Autzinger, Josef Thaler, Heinz Gisslinger, Alois Lang, Miklós Egyed, Niklas Zojer
Journal: Blood (2009)
Radiosensitivity enhancement by dual HER-1/2 inhibitor (GW572016) in SKBR3 human breast carcinoma HER-2+ cell line
Authors: M. Vargas, I. Valduvieco, V. Almendro, J. Domingo-Domenech, E. Ametller, F. Pons, A. Herreros, M. Muñoz, P. Gascón, B. Farrus
Journal: Journal of Clinical Oncology (2008)

22112 Background: Overexpression of the members of HER family has been correlated with high tumor grade, higher metastatic ability and poor prognosis in several epithelial tumors. HER2 amplification has been described in the 25–30% of breast cancer patients and has been associated with chemo and radiotherapy (RT) resistance. Radiosensitivity of a tumor is inversely related to the cellular EGFR (epidermal growth factor receptor) density on its surface. Moreover, RT has also been reported to induce the activation of survival signals through activation of EGFR and HER2. Therefore we hypothesized that the blockage of the survival signal transduction of the HER family by using Lapatinib (GW572016), a selective inhibitor of both EGFR and HER2 TK (tyrosine kinase) activity, may enhance radiation- induced cell killing. The aim of this study was to asses the potential effect of the dual HER-1/2 inhibitor Lapatinib on radiosensitivity. Methods: SKBR3 human breast carcinoma cell line which overexpresses HER2 on the cell surface was used. Lapatinib at different concentrations were used (nM) to determine the IC50 value. Irradiation was carried out at room temperature using 6 MV photons at 300 cGy/min dose-rate with different doses. To avoid the build-up and backscattering effects it was added 15mm up every plate and 110mm down it respectively. RT and Lapatinib effects were characterized alone and in combination to determine the synergistic effects of the treatment. Radiosensitizing effects by the blockage of EGFR and HER2 were determined by a colorimetric MTS assay. HER2 gene expression was determined by the Assay-on-demand (Applied Biosystems). Results: RT increased the HER2 mRNA content in SKBR3 cells. The IC50 of RT alone was achieved at 14 Gy. The IC50 of Lapatinib was 50 nM, however the IC50 combination was obtained with 2 Gy and 20 nM for RT and lapatinib respectively. Conclusions: Lapatinib, a dual HER-1/2 inhibitor, enhance SKBR3 breast cancer HER-2+ cell line radiosensitivity. These results suggest that the combination of both treatments could have a synergistic effect on patients with HER2 positive breast cancer. No significant financial relationships to disclose.
TCT-100 Transcatheter Aortic Valve Replacement in Patients With End-Stage Renal Disease: One Year Outcomes from the CoreValve US Expanded Use Study
Authors: Daniel O'Hair, George Petrossian, Tanvir Bajwa, Stanley J. Chetcuti, G Michael Deeb, Neal Kleiman, Michael J. Reardon
Journal: Journal of the American College of Cardiology (2015)
PET-CT Post–Hepatic Radiation Changes in Gastroesophageal Adenocarcinoma
Authors: Don Nguyen, Rishi Maheshwary, Anuj Rajput, Cassie Tran, Vijay Kudithipudi
Journal: Clinical Nuclear Medicine (2016)

Gastroesophageal junction adenocarcinoma on esophagogastroduodenoscopy biopsy. Initial PET-CT showed no definite evidence of distant metastatic disease. One month after radiation treatment, repeat PET-CT showed interval decrease in size of gastroesophageal mass but new multifocal FDG avidity in the caudate and left hepatic lobes. Correlation with contrast-enhanced CT and US images was negative, making metastasis less likely. Ultrasound-guided biopsy confirmed radiation-induced hepatitis, which caused false positively increased FDG uptake from inflammatory changes.
Survival Disparities in Patients with Lymphoma According to Place of Residence and Treatment Provider: A Population-Based Study
Authors: Fausto R Loberiza, Anthony J Cannon, Dennis D Weisenburger, Julie M. Vose, Matt J. Moehr, Martin A. Bast, Philip Bierman, R. Gregory Bociek, James Olen Armitage
Journal: Blood (2008)
Functionally distinct roles for different miR-155 expression levels through contrasting effects on gene expression, in acute myeloid leukaemia
Authors: N Narayan, L Morenos, B Phipson, S N Willis, G Brumatti, S Eggers, N Lalaoui, L M Brown, H J Kosasih, R C Bartolo, L Zhou, D Catchpoole, R Saffery, A Oshlack, G J Goodall, P G Ekert
Journal: Leukemia (2016)
TCT-661 Low Contrast Dose CTA For TAVR Evaluation Using Central Pulmonary Artery Catheter
Authors: Diljon S. Chahal, Eric Ginsberg, Seth J. Kligerman, Jean Jeudy, Stephen L. Seliger, Adam Meeks, Teng C. Lee, Anuj Gupta
Journal: Journal of the American College of Cardiology (2015)
Assessment of Renal Function in Transfused b-Thalassemia Patients Based on Cystatin C Measurements and Equations.
Authors: Antonios Kattamis, Alexandra Margeli, Eugenia Hantzi, George Paleologos, Athanasia Sergounioti, Athanasia Lourida, Natalia Lazopoulou, Vassilios Ladis, Ioannis Papassotiriou
Journal: Blood (2007)
Targeted EZH2 Inhibitors in Diffuse Large B-Cell Lymphoma (DLBCL): Immunohistochemical and Mutational Profiles of Patients May Determine Candidates for Treatment
Authors: Sydney Dubois, Sylvain Mareschal, Marie Cornic, Jean-Michel Picquenot, Philippe Bertrand, Elodie Bohers, Catherine Maingonnat, Pierre-Julien Viailly, Philippe Ruminy, Marion Alcantara, Christian Bastard, Fabrice Jardin, Herve Tilly
Journal: Blood (2014)
Anti‐inflammatory therapies in atopic dermatitis
Authors: A. Heratizadeh, T. Werfel
Journal: Allergy (2016)

Abstract The pathogenesis of atopic dermatitis ( AD ) is multifactorial and complex. Consequently, clinical signs and symptoms vary strongly depending on individually relevant trigger factors and the stage of the disease. So far, treatment of AD was commonly limited to topical treatment or, in more severe cases, to systemic drugs mostly approved for other indications than AD . However, emerging data on new anti‐inflammatory agents have been published in the recent years. As these new substances specifically focus on immune responses in AD , these are partially considered as possible ‘breakthrough’ in the treatment of AD . Therapeutic strategies of the future appear to be ‘customized’ for inflammation in AD as they target pro‐inflammatory, highly relevant cytokines and cytokine receptors, such as IL ‐4Rα, IL ‐13, IL ‐31, and IL ‐17. Further innovative therapeutic approaches aim to block the function of relevant molecules such as thymic stromal lymphopoietin, chemoattractant‐receptor homologous molecule expressed on Th2 lymphocytes ( CRT h2), and phosphodiesterase ( PDE )‐4 inhibitors. Recently, anti‐inflammatory effects in AD by antagonizing the histamine (H)‐4 receptor have also been detected. Finally, specific immunotherapy is under further investigation as treatment option for AD patients with clinically relevant sensitization.
PD-L1 expression in advanced NSCLC: Primary lesions versus metastatic sites and impact of sample age.
Authors: Anita Midha, Alan Sharpe, Marietta Scott, Jill Walker, Kunyang Shi, Marc Ballas, Marina C Garassino, Naiyer A. Rizvi
Journal: Journal of Clinical Oncology (2016)

3025 Background: Determination of PD-L1 levels in tumors can help establish patient suitability for PD-1/PD-L1 targeted immunotherapies in NSCLC. Biopsies may be taken from different sites (primary or metastatic) and may also vary in age, particularly if archived tissue is used. Understanding the impact of different sample types on PD-L1 expression will help determine suitability for testing. Methods: FFPE samples from 1546 patients screened for the ATLANTIC (NCT02087423) trial were successfully tested using the Ventana PD-L1 IHC (SP263) test positivity cut off ≥ 25% cells with tumor membrane expression. For patients screened for cohort 2, PD-L1 expression was reported in primary versus metastatic lesion, and by age, sex, ethnicity & smoking status. In addition, 88 commercial contemporaneous paired primary & metastatic samples were tested. Results: PD-L1 prevalence by sample age in ATLANTIC < 3 months, 31.2% (n = 1191); ≥ 3 months to 1 year 32.8% (n = 118), 1 - 3 years 29.1% (n = 173), > 3 years 13.3% (n = 83). For 112 patients, both archival & recently acquired (< 3 month) samples were available; concordance with recent samples was highest with archival samples less than 3 years old (76.2%). In patients screened for cohort 2, PD-L1 prevalence did not differ by demographic groups (Table 1). Prevalence in primary & metastatic samples was 35.0% & 33.2% retrospectively (p = 0.647). Concordance between paired contemporaneous commercial primary & metastatic samples was 39/44 (88.6%). Conclusions: PD-L1 expression was not enriched in any demographic group. Similarity of PD-L1 prevalence in metastatic and primary lesions and the concordance between paired samples supports the use of either for determination of PD-L1 status. Data also support use of samples up to 3 years old for determining PD-L1 status, which is relevant if a recent sample is unavailable. Clinical trial information: NCT02087423. Patients screened for ATLANTIC cohort 2 (n = 555) Characteristic (n) PD-L1 Prevalence P value Sex Male (348) 113 (32.5%) 0.835 Female (207) 69 (33.3%) Ethnicity Caucasian (430) 140 (32.6%) 0.699 (Caucasian v Asian) Asian (119) 41 (34.5%) Other (6) 1 (16.7%) Smoking status Smoker (458) 151 (33.0%) 0.846 Non-smoker (97) 31 (32.0%) Age > 65 (222) 76 (34.2%) 0.556 < 65 (333) 106 (31.8%)
Cardiogenic shock in intensive care units: evolution of prevalence, patient profile, management and outcomes, 1997–2012
Authors: Etienne Puymirat, Jean Yves Fagon, Philippe Aegerter, Jean Luc Diehl, Alexandra Monnier, Caroline Hauw‐Berlemont, Florence Boissier, Gilles Chatellier, Bertrand Guidet, Nicolas Danchin, Nadia Aissaoui
Journal: European Journal of Heart Failure (2016)
Face Mask vs Helmet for Noninvasive Ventilation
Authors: Paolo Taccone, Davide Chiumello
Journal: JAMA (2016)

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Preemptive Detection Of JC Virus In Peripheral Blood Of Patients Undergoing Allogeneic Stem Cell Transplantation: A Potential Tool To Prevent Progressive Multifocal Leukoencephalopathy In High-Risk Patients?
Authors: Irit Avivi, Talya Wittmann, Noam Benyamini, Zipora Kra-Oz, Moran Szwarcwort, Ilana Oren, Jacob M. Rowe, Tsila Zuckerman, Netanel Horowitz
Journal: Blood (2013)
Single-Cell Mass Cytometry Analysis of the Human Endocrine Pancreas
Authors: Yue J. Wang, Maria L. Golson, Jonathan Schug, Daniel Traum, Chengyang Liu, Kumar Vivek, Craig Dorrell, Ali Naji, Alvin C. Powers, Kyong-Mi Chang, Markus Grompe, Klaus H. Kaestner
Journal: Cell Metabolism (2016)
Expansion of Inhibitory NK Receptor (CD94/NKG2A)-Expressing CD8 T Cells from Various Blood Mononuclear Cells with Cytolytic Activity Against Primary Leukemic Cells.
Authors: Junji Tanaka, Noriaki Iwao, Tomomi Toubai, Yoko Miura, Naoko Kato, Akio Shigematsu, Keichi Kondo, Shuichi Ota, Masahiro Asaka, Masahiro Imamura
Journal: Blood (2004)
What do ovarian cancer patients expect from follow-up? Results of a survey of the noggo and ago in 1,015 patients
Authors: G. Oskay-Oezcelik, A. du Bois, P. A. Fasching, C. Liebrich, A. Glass, K. Münstedt, S. Mahner, D. Koensgen, W. Lichtenegger, S. Schmidt-Wetzel, J. Sehouli
Journal: Journal of Clinical Oncology (2008)

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