tbuckley/cabot-search huggingface dataset:
Gut microbiota and Toll-like receptors set the stage for cytokine-mediated failure of antibacterial responses in the fibrotic liver
Authors: Christian Kuntzen, Robert F Schwabe
Journal: Gut (2016)

The gut–liver axis is increasingly recognised as a key contributor to chronic liver disease. A failing gut barrier contributes to increased bacterial translocation, which results in an elevated risk of bacterial infection and a chronic inflammatory state that may promote the progression of chronic liver disease and the development of long-term complications such as fibrosis and HCC.1 ,2 The most important clinical consequence of increased translocation is acute bacterial infection, a common cause of hospital admissions and a major contributor to morbidity and mortality in patients with cirrhosis. Moreover, bacterial infections can lead to acute decompensation, often triggering acute-on-chronic liver injury.3 On top of a leaky gut, patients with liver cirrhosis have severe defects in the innate immune system, affecting macrophages, neutrophils and the complement system.4 The liver itself represents an important immunological organ and is the first target of gut-derived bacteria, bacterial pathogen-associated molecular patterns (PAMPs) and food products after they enter the circulation. For this reason, 80% of the body's resident macrophages are found in the liver, where they act as an important component of a firewall, that protects the body from infection from circulating bacteria.5 Following infection, a large proportion of circulating bacteria are phagocytosed by Kupffer cells rather than in the spleen; ablation of macrophages severely hampers clearance of circulating bacteria.5 Together, these findings suggest that the liver rather than the spleen is the main organ involved in the clearance of circulating bacteria. Importantly, the presence of liver fibrosis severely hampers the clearance of circulating bacteria.5 However, the mechanisms that impair the clearance of circulating bacteria in the fibrotic liver remain largely unknown. Better knowledge of the underlying pathways may lead towards novel therapeutic targets for patients with advanced liver disease.

In this issue, …
Estimating National Trends in Inpatient Antibiotic Use Among US Hospitals From 2006 to 2012
Authors: James Baggs, Scott K. Fridkin, Lori A. Pollack, Arjun Srinivasan, John A. Jernigan
Journal: JAMA Internal Medicine (2016)

The rising threat of antibiotic resistance and other adverse consequences resulting from the misuse of antibiotics requires a better understanding of antibiotic use in hospitals in the United States.
Increased Inflammatory Markers and Their Correlations To Clinical Complications In Hemoglobin SC Disease
Authors: Marina Pereira Colella, Erich Vinicius de Paula, Nicola Conran, Joao Machado-Neto, Susan K.P. Quaino, Joyce M. Annichino-Bizzacchi, Fernando Ferreira Costa, Sara Terezinha Olalla-Saad, Fabiola Traina
Journal: Blood (2013)
TET2 Exon 2 Skipping Confers Sensitivity to AraC and Is an Independent Favorable Prognostic Factor in AML Patients Treated with Intensive Chemotherapy
Authors: Aminetou Mint Mohamed, Marie Balsat, Lea Payen-Gay, Delphine Maucort-Boulch, Meyling Cheok, Hussein Mortada, Didier Auboeuf, Mohamed El-Hamri, Catherine Koering, Isabelle Tigaud, Charles Dumontet, Emeline Cros, Pascale Flandrin-Gresta, Olivier Nibourel, Claude Preudhomme, Xavier Thomas, Franck E. Nicolini, Francoise Solly, Denis Guyotat, Lydia Campos, Franck Mortreux, Eric Wattel
Journal: Blood (2014)
Analysis of Patient (Pt) Outcomes By Prior Treatment and Depth of Response in Stratus (MM-010), a Phase 3b Study of Pomalidomide + Low-Dose Dexamethasone (POM + LoDEX) in Patients (Pts) with Relapsed/Refractory Multiple Myeloma (RRMM)
Authors: Philippe Moreau, Antonio Palumbo, Paolo Corradini, Michele Cavo, Michel Delforge, Katja C. Weisel, Enrique M. Ocio, Annamaria Cafro, Christoph Rollig, Stefan Knop, Felipe de Arriba, Mathew Simcock, Neil Miller, Ana Slaughter, Latisha Watkins, Jennifer Herring, Tsvetan Biyukov, Teresa Peluso, Mohamed H Zaki, Meletios A. Dimopoulos
Journal: Blood (2015)
Bortezomib-Induced Proinflammatory Macrophages Contribute to Multiple Myeloma Cell Aggressiveness
Authors: Ofrat Beyar Katz, Neta Ben-Tsedek, Irit Avivi, Dror Alishekevitz, Michael Timaner, Valeria Miller, Moshit Lindzen, Yosef Yarden, Yuval Shaked
Journal: Blood (2015)
Validation of the Galad Score for Hepatocellular Carcinoma Diagnosis in a Us Cohort
Authors: J.D. Yang, J. Dai, B. Addissie, M.H. Nguyen, A.S. Befeler, R. Reddy, M.E. Schwartz, D.M. Harnois, G.Y.J. Gores, Z. Feng, J.A. Marrero, L.R. Roberts
Journal: Journal of Hepatology (2016)
Interferon-Free Daa Regimens Decrease Portal Pressure and Halt Histological Necroinflammation in HIV/HCV coinfected Patients
Authors: P. Schwabl, M. Mandorfer, S. Steiner, B. Scheiner, T. Bucsics, M. Aichelburg, K. Grabmeier-Pfistershammer, W. Sieghart, A. Ferlitsch, M. Trauner, T. Reiberger, M. Peck-Radosavljevic
Journal: Journal of Hepatology (2016)
ARDS, up close and personal
Authors: Mark Griffiths, Alastair Proudfoot
Journal: Thorax (2016)

The acute respiratory distress syndrome (ARDS) was first reported in a case series from Denver in 1967.1 Forty-five years later, the syndrome was reborn: the ‘Berlin’ definition captures patients with a mortality of 24% rising to 48% in the group of patients with the most severe respiratory failure.2 Survivors commonly suffer from muscle weakness and neuropsychiatric problems, such that fewer than 50% have returned to work 12 months after leaving intensive care.3 ARDS is important both clinically and financially. It is a not uncommon contributor to the deaths of critically ill patients of all ages4 and survivors commonly suffer from muscle weakness and neuro-psychiatric problems, such that fewer than 50% have returned to work 12 months after leaving intensive care.3 ,5

The onset of ARDS can be ascribed to two processes resulting from acute inflammation or injury at the lung's gas exchange surface: the alveolar–capillary membrane. These processes increase the permeability of the membrane associated with the recruitment of neutrophils into the airspace. The resulting acute inflammatory exudate inactivates surfactant, leading to collapse and consolidation with progressive loss of functioning lung. This would be well tolerated physiologically if the inflammatory process did not paralyse the lung's means of preventing ventilation–perfusion mismatch: hypoxic pulmonary vasoconstriction. The combination of these factors causes profound hypoxaemia accompanied by pulmonary oedema. The latter mechanism accounts for the fact that as a rule patients with ARDS are considerably more hypoxaemic than those with heart failure with similar radiographic appearances.

Since its recognition, much has been learnt about …
Vitamin D Receptor is Up-Regulated in NAFLD Hepatocytes and is Required for High Fat Diet-Induced Steatosis in APOE-/- Mice Liver
Authors: R. Jover, M. Bozic, C. Guzmán, S. Sánchez-Campos, C. García-Monzón, J.M. Valdivielso
Journal: Journal of Hepatology (2016)
Allogeneic Hematopoietic Cell Transplantation for Severe Epidermolysis Bullosa: Impact of Conditioning Regimen and Stem Cell Source On Outcomes
Authors: Jakub Tolar, John A. McGrath, Mark J. Osborn, Kristen P. Hook, Douglas R. Keene, Maria K. Hordinsky, Bruce R. Blazar, John E. Wagner
Journal: Blood (2012)
A Case of Lung Adenocarcinoma Resistant to Crizotinib Harboring a Novel EML4-ALK Variant, Exon 6 of EML4 Fused to Exon 18 of ALK
Authors: Satoshi Anai, Masafumi Takeshita, Nobuhisa Ando, Yuuki Ikematsu, Shohei Mishima, Koichi Ishida, Kouji Inoue
Journal: Journal of Thoracic Oncology (2016)
Genetic Variations in CYP2B6 and Risk of Cyclophosphamide Toxicity in Patients Undergoing Myeloablative Stem Cell Transplantation.
Authors: Stacy E Melanson, Joseph H. Antin, Michael H. Court, Vincent Ho, Jerome Ritz, Haesook T. Kim, Frank C Kuo, Janina A Longtine, Petr Jarolim
Journal: Blood (2008)
The Unfolded Protein Response Underlies Microenvironmental Stress-Induced Phenotype Switching Leading to Stemness and Chemoresistance in Human Hepatocellular Carcinoma
Authors: Y.-P. Vandewynckel, O. Govaere, A. Vandierendonck, D. Laukens, L. Devisscher, A. Paridaens, E. Bogaerts, S. Raevens, X. Verhelst, C. Van Steenkiste, L. Libbrecht, C. Ampe, M. Van Troys, A. Geerts, T. Roskams, H. Van Vlierberghe
Journal: Journal of Hepatology (2016)
SU2C phase Ib study of pan-PI3K inhibitor BKM120 with letrozole in ER+/HER2- metastatic breast cancer (MBC).
Authors: Ingrid A. Mayer, Vandana Gupta Abramson, Justin M. Balko, Steven J. Isakoff, Maria Gabriela Kuba, Melinda Sanders, Andres Forero-Torres, Jeffrey T. Yap, Annick D. Van Den Abbeele, Yisheng Li, Carlos L. Arteaga, Eric P. Winer
Journal: Journal of Clinical Oncology (2012)

510 Background: Mutations in PIK3CA, the gene encoding the p110a subunit of PI3K, have been associated with antiestrogen resistance in ER+ BC. In general, antiestrogen-resistant cancers retain ER and responsiveness to estradiol. This suggests that treatment of ER+/PI3K mutant BC should include PI3K inhibitors plus antiestrogens. Methods: We conducted a phase Ib trial of letrozole (2.5 mg/d) with the pan-PI3K inhibitor BKM120 in post-menopausal patients (pts) with ER+/HER2 MBC. BKM120 (100 mg/d) was given continuously (Arm A) or intermittently (5 on/2 off days; Arm B). Upon toxicity, BKM120 was reduced to 80 and 60 mg/d. Treatment continued until unacceptable toxicity or disease progression. Disease was assessed every 2 months. FDG-PET was done at baseline and at 2 weeks in all pts in Arm A. Results: Fifty-one pts were accrued; 49 had progressed on an AI previously. Median age was 56 years (range 34-77); 95% had bone and 70% visceral metastases. Toxicities and outcomes are summarized in the table. The only DLT* in Arm A and B were transaminitis and depression, respectively; both at 100 mg. Over 50% of Arm A pts had &gt;25% reduction in their peak SUV at the 2-week FDG-PET. Pts who did not exhibit a metabolic response by FDG-PET progressed rapidly on therapy. Three pts in Arm A had a PI3K mutation; one of them has had stable disease on treatment for &gt;12 months. Conclusions: The combination of letrozole/ BKM120 is safe in pts with AI-refractory ER+/HER2 MBC. Arm B is ongoing and will be updated at the meeting. All tumor biopsies will be analyzed for PI3K pathway alterations. FDG-PET at 2 weeks appears to be a useful pharmacodynamic biomarker of PI3K pathway inhibition in most patients. Its value in predicting treatment response remains to be determined. [Table: see text] [Table: see text]
NRG Oncology RTOG 0415: A randomized phase III non-inferiority study comparing two fractionation schedules in patients with low-risk prostate cancer.
Authors: W. Robert Lee, James J. Dignam, Mahul Amin, Deborah Bruner, Daniel Low, Gregory P. Swanson, Amit Shah, David D'Souza, Jeff M. Michalski, Ian Dayes, Samantha A. Seaward, William Adrian Hall, Paul L. Nguyen, Thomas Michael Pisansky, Sergio Faria, Yuhchyau Chen, Bridget F. Koontz, Rebecca Paulus, Howard M. Sandler
Journal: Journal of Clinical Oncology (2016)

1 Background: To determine whether the efficacy of a hypofractionated (H) schedule is no worse than a conventional (C) schedule in men with low-risk prostate cancer. Methods: From April 2006 to December 2009, one thousand one hundred fifteen men with low-risk prostate cancer (clinical stage T1-2a, Gleason ≤ 6, PSA &lt; 10) were randomly assigned 1:1 to a conventional (C) schedule (73.8 Gy in 41 fractions over 8.2 weeks) or to a hypofractionated (H) schedule (70 Gy in 28 fractions over 5.6 weeks). The trial was designed to establish with 90% power and alpha = 0.05 that (H) results in 5-year disease-free survival (DFS) that is not lower than (C) by more than 7% (hazard ratio (HR) &lt; 1.52). Secondary endpoints include freedom from biochemical recurrence (FFBR) and overall survival. At the third planned interim analysis (July 2015), the NRG Oncology Data Monitoring Committee recommended that the results of the trial be reported. Results: One thousand one hundred and one protocol eligible men were randomized: 547 to C and 554 to H. Median follow-up is 5.9 years. Baseline characteristics are not different according to treatment arm. At the time of analysis 185 DFS events have been observed; 99 in the C arm and 86 in the H arm. The estimated 7-year disease-free survival is 75.6% (95% CI 70.3, 80.1) in the C arm and 81.8% (77.5, 85.3) in the H arm. The DFS HR (C/H) is 0.85 (0.64, 1.14). Comparison of biochemical recurrence (HR = 0.77, (0.51, 1.17)) and overall survival (HR = 0.95, (0.65, 1.41)) also met protocol non-inferiority criteria. Grade ≥ 3 GI toxicity is 3.0% (C) vs. 4.6% (H), Relative risk (RR) for H vs. C 1.53, (95% CI 0.86, 2.83); grade ≥ 3 GU toxicity is 4.5% (C) vs. 6.4% (H), RR = 1.43 (0.86,2.37). Conclusions: In men with low-risk prostate cancer, 70 Gy in 28 fractions over 5.6 weeks is non-inferior to 73.8 Gy in 41 fractions over 8.2 weeks. Clinical trial information: NCT00331773.
Alantolactone selectively ablates acute myeloid leukemia stem and progenitor cells
Authors: Yahui Ding, Huier Gao, Yu Zhang, Ye Li, Neil Vasdev, Yingdai Gao, Yue Chen, Quan Zhang
Journal: Journal of Hematology & Oncology (2016)

Abstract Background The poor outcomes for patients diagnosed with acute myeloid leukemia (AML) are largely attributed to leukemia stem cells (LSCs) which are difficult to eliminate with conventional therapy and responsible for relapse. Thus, new therapeutic strategies which could selectively target LSCs in clinical leukemia treatment and avoid drug resistance are urgently needed. However, only a few small molecules have been reported to show anti-LSCs activity. Methods The aim of the present study was to identify alantolactone as novel agent that can ablate acute myeloid leukemia stem and progenitor cells from AML patient specimens and evaluate the anticancer activity of alantolactone in vitro and in vivo. Results The present study is the first to demonstrate that alantolactone, a prominent eudesmane-type sesquiterpene lactone, could specifically ablate LSCs from AML patient specimens. Furthermore, in comparison to the conventional chemotherapy drug, cytosine arabinoside (Ara-C), alantolactone showed superior effects of leukemia cytotoxicity while sparing normal hematopoietic cells. Alantolactone induced apoptosis with a dose-dependent manner by suppression of NF-kB and its downstream target proteins. DMA-alantolactone, a water-soluble prodrug of alantolactone, could suppress tumor growth in vivo. Conclusions Based on these results, we propose that alantolactone may represent a novel LSCs-targeted therapy and eudesmane-type sesquiterpene lactones offer a new scaffold for drug discovery towards anti-LSCs agents.
Vigilance and Wake Eeg Architecture in Simulated Hyperammonaemia: A Pilot Study on the Effects of Lola and Caffeine
Authors: M. Garrido, J. Skorucak, D. Raduazzo, M. Turco, G. Spinelli, P. Angeli, P. Amodio, P. Achermann, S. Montagnese
Journal: Journal of Hepatology (2016)
Immune Reconstitution in Pregnancy and Chronic Hepatitis B – Is Post-Delivery Flare Associated with Evolution in HBV DNA viral Replication and HBsAg Levels in Untreated Patients Post Partum?
Authors: I. Carey, M.-A. McLeod, M. Bruce, M. Horner, T. Bowyer, K. Oakes, A. Mrzljak, R. Basuroy, S. Verma, K. Agarwal
Journal: Journal of Hepatology (2016)
Predictors of response of U.S. veterans to treatment for the hepatitis C virus
Authors: Thomas R. Riley
Journal: Hepatology (2007)

We read with interest the article by Backus et al.1 in which they describe factors that may predict sustained virologic response in a U.S. veteran population. The large nature of the review makes the study a major undertaking, with over 9022 records reviewed. Much interesting and important information can be gained from such undertakings. The authors, however, emphasize a difference that they have found between pegylated interferon 2A and pegylated interferon 2B. The retrospective study design is inadequate to address such a difference. The study lacks a table or analysis of the group characteristic differences between those treated with 2A and those treated with 2B. Clearly, we would need to know before making any reliable inference from these data whether the ribavirin doses were equal between groups, whether African Americans were equally represented, and whether the genotype differed between groups. The authors do share with us that 98% of patients got the appropriate 2A dose, whereas only 70% got the appropriate 2B dose. This is just a teaser for how many other differences might be found between the two groups with a careful analysis, which could uncover possible confounders.2 The authors seem perplexed and unable to explain their observed differences, as the readers should be. These data should be taken with the proverbial "grain of salt" that the method for obtaining the data calls for. Thomas R. Riley III M.D.*, * Hershey Medical Center, Hershey, PA.
Polymorphismus in the Interleukin (IL)-1 Gene Cluster Influence the Inflammatory Burden in Patients with Decompensated Cirrhosis and Acute-On-Chronic Liver Failure
Authors: J.A. Quiles, E. Titos, M. Casulleras, C. López-Vicario, B. Rius, A. Lopategi, A. de Gottardi, M. Bernardi, I. Graziadei, H. Gronbaek, P. Ginès, V. Arroyo, J. Clària
Journal: Journal of Hepatology (2016)
Inhibition of Connexin Hemichannels Alleviates Acetaminophen-Induced Hepatotoxicity in Mouse
Authors: M. Maes, S.C. Yanguas, J. Willebrords, T.C. da Silva, M. Lebosky, I.V. Pereira, H. Jaeschke, B. Cogliati, M. Vinken
Journal: Journal of Hepatology (2016)
T Cell-Independent Hepatic Inflammation in Viral-Related Liver Cirrhosis and Hepatocellular Carcinoma
Authors: A. Tan-Garcia, L.-E. Wai, D. Zheng, E. Ceccarello, A.T. Tan, N. Banu, M. Hong, A. Chia, K.C. Tan, K.H. Lee, Q. Chen, C.-A. Dutertre, A. Bertoletti
Journal: Journal of Hepatology (2016)
Survival and Response Outcomes to Different Treatment Schedules in CML Patients Starting Therapy with Imatinib. Results from the CML Spanish Registry (RELMC)
Authors: Luis Felipe Casado, Isabel Massague, Pilar Giraldo, Manuel Perez-Encinas, Raquel De Paz, Joaquín Martínez-López, Guiomar Bautista, Santiago Osorio, Maria José Requena, Luis Palomera, Maria Jesús Peñarrubia, Carmen Calle, Begoña Maestro, Juan Luis Steegmann
Journal: Blood (2010)
Acceptance, Yield and Feasibility of Attaching HCV Birth Control Screening to Colorectal Cancer Screening in Spain
Authors: D. Bonillo-Cambrodon, F.-J. García-Alonso, A. Algaba, A. Bermejo-Abati, J. García-Martínez, P. Valer, B. Piqueras-alcol, F. Bermejo
Journal: Journal of Hepatology (2016)
Acute myeloid leukaemia
Authors: Asim Khwaja, Magnus Bjorkholm, Rosemary E. Gale, Ross L. Levine, Craig T. Jordan, Gerhard Ehninger, Clara D. Bloomfield, Eli Estey, Alan Burnett, Jan J. Cornelissen, David A. Scheinberg, Didier Bouscary, David C. Linch
Journal: Nature Reviews Disease Primers (2016)
Which Strategy of Immunoablative Therapy with Autologous Stem Cell Transplantation (ASCT) Is Preferable in Multiple Sclerosis (MS) Patients?.
Authors: Yury L. Shevchenko, Andrei A. Novik, Alexey N. Kuznetcov, Boris A. Afanasiev, Igor A. Lisukov, Oleg A. Rykavicin, Alexandr A. Myasnikov, Tatyana I. Ionova, Vladimir J. Melnichenko, Denis A. Fedorenko, Anton V. Kishtovich, Roman A. Ivanov, Gary J. Gorodokin
Journal: Blood (2007)
The External Validation of Hong Kong Liver Cancer Staging System for Prediction of Survival with Korean Multicenter HCC Patients: Comparing with Barcelona Clinic Liver Cancer Staging System
Authors: Y.-S. Lee, J.H. Kim, H.R. Kim, Y.J. Yoo, T.S. Kim, S.H. Kang, S.J. Suh, Y.K. Jung, Y.S. Seo, H.J. Yim, J.E. Yeon, K.S. Byun
Journal: Journal of Hepatology (2016)
Polycystic Liver Disease Patients with Underlying Diagnosis of Polycystic Kidney Disease are More Likely to Undergo Liver Transplantation than Patients with Isolated Polycystic Liver Disease
Authors: H.M.A. D’Agnolo, W. Kievit, K. van Munster, J. van der Laan, F. Nevens, J. Drenth
Journal: Journal of Hepatology (2016)
Timing of cellular changes during ischemia-reperfusion injury in mice lung
Authors: Nele Geudens, Bart Vanaudenaerde, Arne Neyrinck, Filip Rega, Caroline Van De Wauwer, Nicole Jannis, Geert Verleden, Eric Verbeken, Antoon Lerut, Dirk Van Raemdonck
Journal: European Respiratory Journal (2005)
Obesity treatment—are personalised approaches missing the point?
Authors: Alison E Tedstone
Journal: BMJ (2016)

The causes of the obesity epidemic may have little to do with gene profiles

Many companies offer personalised weight loss plans tailored to our DNA, selling the idea that the effectiveness of dieting is predetermined. There is a degree of plausibility behind this, as numerous genes have been associated with increased body weight.1 In reality, the extent to which genes determine the ability to lose weight remains unclear. The study by Livingstone et al (doi:10.1136/bmj.i4707)2 represents a substantial step towards answering this, at least for the FTO gene, the allele currently associated with the largest variance in body mass index.3 The authors conducted a systematic review and meta-analysis using data from almost 10 000 participants from randomised control trials to test the relation between the FTO gene and weight loss interventions. They found no relation between the FTO gene and the ability to lose weight. This contradicts a previous meta-analysis, not based on data from individuals, which found a small but significant increased responsiveness to weight management interventions (of 0.7 kg) in people homozygous for the FTO allele.4

The authors acknowledge several limitations in their …