tbuckley/cabot-search huggingface dataset:
Long term efficacy of pirfenidone therapy in patients with idiopathic pulmonary fibrosis (IPF)
Authors: Takuya Takaiwa, Hiromasa Tachibana, Machiko Arita, Tadashi Ishida
Journal: European Respiratory Journal (2014)

Background:Pirfenidone has been used for the treatment of IPF in Japan since 2008. However, the long term efficacy of the drug remains unclear.

Purpose:To evaluate the efficacy of pirfenidone therapy for ≥6 months and identify the predictive factors for drug response

Methods:Between July 2010 and August 2013, 38 patients underwent pirfenidone therapy for clinico-radiologically diagnosed IPF based on an official ATS/ERS/JRS/ALAT statement published in 2011. We evaluated the efficacy on the chronological changes of percent forced vital capacity (%FVC), percent diffusing capacity for carbon monoxide (%DLCO), and composite physiologic index (CPI). Patients were divided into two groups; patients who continued the therapy for ≥6 months, tolerable group, and patients who withdrew the therapy, intolerable group. We investigated baseline characteristics between two groups.

Results:Twenty-five patients continued the therapy for ≥6 months. In the tolerable group, the mean changes of %FVC were -2.872% (-6-0month), +2.565% (0-6months), -1.017% (6-12months), and -6.398% (12-18months), and the mean changes of %DLCO and CPI were similar.In the same group, linear mixed-effects model analysis showed that pirfenidone significantly improved %FVC at 6 months, %DLCO at 6 and 12 months, and CPI at 6 and 12 months. In the tolerable group, the baseline %FVC and %DLCO were significantly higher (p=0.004, 0.033 respectively), and the baseline CPI was significantly lower (p=0.011) than in the intolerable group.

Conclusion:Our results suggest that pirfenidone is effective for 12 months but ineffective at 18 months and that drug response is better in patients with good pulmonary function on the baseline.
In a general population there seems to be a link between subclinical atherosclerosis and lung hyperinflation
Authors: Alexander Lorenzo Hartmann, Robab Breyer-Kohansal, Marie-Kathrin Breyer, Sylvia Hartl, Andrea Schrott, Otto Chris Burghuber
Journal: European Respiratory Journal (2013)

Background   In patients with COPD it has been shown that there is a correlation between the degree of lung hyperinflation and subclinical atherosclerosis measured by carotid-femoral PWV (pulse wave velocity-PWV). We wondered wheter we could demonstrate this correlation also in a general population cohort.   Methods   In an interim analysis of the ongoing Austrian LEAD (Lung hEart sociAl body) study, a single-center, longitudinal, open labeled, observational, population based cohort study, 1147 participants were included (female 54,9%, mean age 52,8 yrs). In addition to PWV also age, parameters of lipid profil (HDL plasma level), systemic inflammation (hsCRP), and lung hyperinflation (RV%/TLC) were measured.   Results   In total 7,2% (n=83) of participants showed elevated levels of PWV, defined as > 12m/second indicating subclinical atherosclerosis. Compared to participants with normal PWV, those with elevated PWV were older (67,2+/-8,0 vs 51,7+/-15,7; p=0.0051), had higher HDL plasma levels 67,3mg/dl+/-18,6 vs. 62,1mg/dl +/-16,9; p=0.05), higher hsCRP plasma levels (3,2mg/dl +/- 4,4 vs. 2,1mg/dl +/-3,9; p=001), and increased RV%TLC post lysis (40,8% +/-6,8 vs. 34,9%+/-7,7;p=0.000). However, in a multivariant analysis, only age correlated significantly with PWV, possibly due to the small sample size.   Conclusion   In a general population cohort, subclinical atherosclerosis seems not only be linked to age, lipid profil and systemic inflammation, but also to lung hyperinflation.
FGF21 Regulates Sweet and Alcohol Preference
Authors: Saswata Talukdar, Bryn M. Owen, Parkyong Song, Genaro Hernandez, Yuan Zhang, Yingjiang Zhou, William T. Scott, Bhavna Paratala, Tod Turner, Andrew Smith, Barbara Bernardo, Christian P. Müller, Hao Tang, David J. Mangelsdorf, Bryan Goodwin, Steven A. Kliewer
Journal: Cell Metabolism (2015)
KIAA0556 is a novel ciliary basal body component mutated in Joubert syndrome
Authors: Anna A. W. M. Sanders, Erik de Vrieze, Anas M. Alazami, Fatema Alzahrani, Erik B. Malarkey, Nasrin Sorusch, Lars Tebbe, Stefanie Kuhns, Teunis J. P. van Dam, Amal Alhashem, Brahim Tabarki, Qianhao Lu, Nils J. Lambacher, Julie E. Kennedy, Rachel V. Bowie, Lisette Hetterschijt, Sylvia van Beersum, Jeroen van Reeuwijk, Karsten Boldt, Hannie Kremer, Robert A. Kesterson, Dorota Monies, Mohamed Abouelhoda, Ronald Roepman, Martijn H. Huynen, Marius Ueffing, Rob B. Russell, Uwe Wolfrum, Bradley K. Yoder, Erwin van Wijk, Fowzan S. Alkuraya, Oliver E. Blacque
Journal: Genome biology (2015)

Joubert syndrome (JBTS) and related disorders are defined by cerebellar malformation (molar tooth sign), together with neurological symptoms of variable expressivity. The ciliary basis of Joubert syndrome related disorders frequently extends the phenotype to tissues such as the eye, kidney, skeleton and craniofacial structures. Using autozygome and exome analyses, we identified a null mutation in KIAA0556 in a multiplex consanguineous family with hallmark features of mild Joubert syndrome. Patient-derived fibroblasts displayed reduced ciliogenesis potential and abnormally elongated cilia. Investigation of disease pathophysiology revealed that Kiaa0556 -/- null mice possess a Joubert syndrome-associated brain-restricted phenotype. Functional studies in Caenorhabditis elegans nematodes and cultured human cells support a conserved ciliary role for KIAA0556 linked to microtubule regulation. First, nematode KIAA0556 is expressed almost exclusively in ciliated cells, and the worm and human KIAA0556 proteins are enriched at the ciliary base. Second, C. elegans KIAA0056 regulates ciliary A-tubule number and genetically interacts with an ARL13B (JBTS8) orthologue to control cilium integrity. Third, human KIAA0556 binds to microtubules in vitro and appears to stabilise microtubule networks when overexpressed. Finally, human KIAA0556 biochemically interacts with ciliary proteins and p60/p80 katanins. The latter form a microtubule-severing enzyme complex that regulates microtubule dynamics as well as ciliary functions. We have identified KIAA0556 as a novel microtubule-associated ciliary base protein mutated in Joubert syndrome. Consistent with the mild patient phenotype, our nematode, mice and human cell data support the notion that KIAA0556 has a relatively subtle and variable cilia-related function, which we propose is related to microtubule regulation.
National Standards for Diabetes Self-Management Education
Authors: Martha M. Funnell, Tammy L. Brown, Belinda P. Childs, Linda B. Haas, Gwen M. Hosey, Brian Jensen, Melinda Maryniuk, Mark Peyrot, John D. Piette, Diane Reader, Linda M. Siminerio, Katie Weinger, Michael A. Weiss
Journal: Diabetes Care (2007)
Alemtuzumab As Pre-Conditioning Is Safe and Feasible in Patients with T-Cell Lymphoid Neoplasms Undergoing Allogeneic Stem Cell Transplantation
Authors: Sara Lozano, Amaya Zabalza, Intza Aoiz, Mohamed Hamdi Djatri, Pedro Arregui, Ivan Quispe, Mari Cruz Montoya, Montserrat Alvarellos, Patricia Garcia Ramirez, Katy Perez Equiza, Ana Gorosquieta, Eduardo Olavarria
Journal: Blood (2014)
Multi-Institutional Phase II Study of High-Dose Hypofractionated Proton Beam Therapy in Patients With Localized, Unresectable Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma
Authors: Theodore S. Hong, Jennifer Y. Wo, Beow Y. Yeap, Edgar Ben-Josef, Erin I. McDonnell, Lawrence S. Blaszkowsky, Eunice L. Kwak, Jill N. Allen, Jeffrey W. Clark, Lipika Goyal, Janet E. Murphy, Milind M. Javle, John A. Wolfgang, Lorraine C. Drapek, Ronald S. Arellano, Harvey J. Mamon, John T. Mullen, Sam S. Yoon, Kenneth K. Tanabe, Cristina R. Ferrone, David P. Ryan, Thomas F. DeLaney, Christopher H. Crane, Andrew X. Zhu
Journal: Journal of Clinical Oncology (2015)

To evaluate the efficacy and safety of high-dose, hypofractionated proton beam therapy for hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC).In this single-arm, phase II, multi-institutional study, 92 patients with biopsy-confirmed HCC or ICC, determined to be unresectable by multidisciplinary review, with a Child-Turcotte-Pugh score (CTP) of A or B, ECOG performance status of 0 to 2, no extrahepatic disease, and no prior radiation received 15 fractions of proton therapy to a maximum total dose of 67.5 Gy equivalent. Sample size was calculated to demonstrate > 80% local control (LC) defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 criteria at 2 years for HCC patients, with the parallel goal of obtaining acceptable precision for estimating outcomes for ICC.Eighty-three patients were evaluable: 44 with HCC, 37 with ICC, and two with mixed HCC/ICC. The CTP score was A for 79.5% of patients and B for 15.7%; 4.8% of patients had no cirrhosis. Prior treatment had been given to 31.8% of HCC patients and 61.5% of ICC patients. The median maximum dimension was 5.0 cm (range, 1.9 to 12.0 cm) for HCC patients and 6.0 cm (range, 2.2 to 10.9 cm) for ICC patients. Multiple tumors were present in 27.3% of HCC patients and in 12.8% of ICC patients. Tumor vascular thrombosis was present in 29.5% of HCC patients and in 28.2% of ICC patients. The median dose delivered to both HCC and ICC patients was 58.0 Gy. With a median follow-up among survivors of 19.5 months, the LC rate at 2 years was 94.8% for HCC and 94.1% for ICC. The overall survival rate at 2 years was 63.2% for HCC and 46.5% ICC.High-dose hypofractionated proton therapy demonstrated high LC rates for HCC and ICC safely, supporting ongoing phase III trials of radiation in HCC and ICC.
Admission glucose and in-hospital mortality in patients with acute myocardial infarction, with and without diabetes, from 2001 to 2011 (the China PEACE-Retrospective Acute Myocardial Infarction Study): a retrospective analysis
Authors: Shi Zhao, Karthik Murugiah, Xi Li, Jing Li, Na Li, Zihui Xu, Chen Cheng, Hong Mao, Qing Wang, Harlan M Krumholz, Lixin Jiang
Journal: The Lancet (2015)
Poly(lactide-co-glycolide) microspheres for MRI-monitored delivery of sorafenib in a rabbit VX2 model
Authors: Jeane Chen, Sarah B. White, Kathleen R. Harris, Weiguo Li, Jonathan W.T. Yap, Dong-Hyun Kim, Robert J. Lewandowski, Lonnie D. Shea, Andrew C. Larson
Journal: Biomaterials (2015)
P0094 : Impaired 11β-hydroxysteroid dehydrogenase type 2 activity contributes to renal sodium avidity in human cirrhosis
Authors: A. Dam Fialla, H.C. Thiesson, P. Bie, P.H. Hovind, O.B. Schaffalitzky de Muckadell, A. Krag
Journal: Journal of Hepatology (2015)
Adaptive Servo-Ventilation for Central Sleep Apnea in Systolic Heart Failure
Authors: Martin R. Cowie, Holger Woehrle, Karl Wegscheider, Christiane Angermann, Marie-Pia d’Ortho, Erland Erdmann, Patrick Levy, Anita K. Simonds, Virend K. Somers, Faiez Zannad, Helmut Teschler
Journal: New England Journal of Medicine (2015)

Central sleep apnea is associated with poor prognosis and death in patients with heart failure. Adaptive servo-ventilation is a therapy that uses a noninvasive ventilator to treat central sleep apnea by delivering servo-controlled inspiratory pressure support on top of expiratory positive airway pressure. We investigated the effects of adaptive servo-ventilation in patients who had heart failure with reduced ejection fraction and predominantly central sleep apnea.We randomly assigned 1325 patients with a left ventricular ejection fraction of 45% or less, an apnea-hypopnea index (AHI) of 15 or more events (occurrences of apnea or hypopnea) per hour, and a predominance of central events to receive guideline-based medical treatment with adaptive servo-ventilation or guideline-based medical treatment alone (control). The primary end point in the time-to-event analysis was the first event of death from any cause, lifesaving cardiovascular intervention (cardiac transplantation, implantation of a ventricular assist device, resuscitation after sudden cardiac arrest, or appropriate lifesaving shock), or unplanned hospitalization for worsening heart failure.In the adaptive servo-ventilation group, the mean AHI at 12 months was 6.6 events per hour. The incidence of the primary end point did not differ significantly between the adaptive servo-ventilation group and the control group (54.1% and 50.8%, respectively; hazard ratio, 1.13; 95% confidence interval [CI], 0.97 to 1.31; P=0.10). All-cause mortality and cardiovascular mortality were significantly higher in the adaptive servo-ventilation group than in the control group (hazard ratio for death from any cause, 1.28; 95% CI, 1.06 to 1.55; P=0.01; and hazard ratio for cardiovascular death, 1.34; 95% CI, 1.09 to 1.65; P=0.006).Adaptive servo-ventilation had no significant effect on the primary end point in patients who had heart failure with reduced ejection fraction and predominantly central sleep apnea, but all-cause and cardiovascular mortality were both increased with this therapy. (Funded by ResMed and others; SERVE-HF ClinicalTrials.gov number, NCT00733343.).
Murinization of an anti-GITR IgG2c antibody DTA-1 inhibits immunogenicity-mediated anaphylaxis in C57BL/6J mice
Authors: Hamsell Alvarez, Nicole Belmar, Melvin Fox, Josue Samayoa, Sarah Chan, Diane Hollenbaugh, Fiona Harding
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Recent advances in Immuno-Oncology (IO) have shown that the immune system can be activated to induce long term durable anti-tumor responses. For IO drug development, immune activation is typically explored using rat surrogate antibodies in immunocompetent mouse models. While these
Erratum to: European Resuscitation Council and European Society of Intensive Care Medicine 2015 guidelines for post-resuscitation care
Authors: Jerry P. Nolan, Jasmeet Soar, Alain Cariou, Tobias Cronberg, Véronique R. M. Moulaert, Charles D. Deakin, Bernd W. Bottiger, Hans Friberg, Kjetil Sunde, Claudio Sandroni
Journal: Intensive Care Medicine (2015)
Safety and Clinical Activity Of Crizotinib In Patients With ALK-Rearranged Hematologic Malignancies
Authors: Carlo Gambacorti-Passerini, Keizo Horibe, Fadi Braiteh, Hui-qiang Huang, Yuankai Shi, Matthew H Taylor, Nicoletta Brega, Jolanda Paolini, Paulina Selaru, Tae Min Kim
Journal: Blood (2013)
Hemovascular Progenitors in the Kidney Require Sphingosine-1-Phosphate Receptor 1 for Vascular Development
Authors: Yan Hu, Minghong Li, Joachim R. Göthert, R. Ariel Gomez, Maria Luisa S. Sequeira-Lopez
Journal: Journal of the American Society of Nephrology (2015)

The close relationship between endothelial and hematopoietic precursors during early development of the vascular system suggested the possibility of a common yet elusive precursor for both cell types. Whether similar or related progenitors for endothelial and hematopoietic cells are present during organogenesis is unclear. Using inducible transgenic mice that specifically label endothelial and hematopoietic precursors, we performed fate-tracing studies combined with colony-forming assays and crosstransplantation studies. We identified a progenitor, marked by the expression of helix-loop-helix transcription factor stem cell leukemia (SCL/Tal1). During organogenesis of the kidney, SCL/Tal1(+) progenitors gave rise to endothelium and blood precursors with multipotential colony-forming capacity. Furthermore, appropriate morphogenesis of the kidney vasculature, including glomerular capillary development, arterial mural cell coating, and lymphatic vessel development, required sphingosine 1-phosphate (S1P) signaling via the G protein-coupled S1P receptor 1 in these progenitors. Overall, these results show that SCL/Tal1(+) progenitors with hemogenic capacity originate and differentiate within the early embryonic kidney by hemovasculogenesis (the concomitant formation of blood and vessels) and underscore the importance of the S1P pathway in vascular development.
The experience of a referral centre and literature overview of GIST and carcinoid tumours in inflammatory bowel diseases
Authors: Gianluca Pellino, Rosa Marcellinaro, Giuseppe Candilio, G. Serena De Fatico, Elia Guadagno, Severo Campione, Giuseppe Santangelo, Alfonso Reginelli, Guido Sciaudone, Gabriele Riegler, Silvestro Canonico, Francesco Selvaggi
Journal: International Journal of Surgery (2015)
Preliminary association of circulating tumor cells (CTCs) pre- and post-AdHER2 dendritic cell vaccination with overall survival in patients with metastatic HER2+ solid tumors
Authors: Yusuke Tomita, Jane Trepel, Min-Jung Lee, Sunmin Lee, Jay A Berzofsky, Lauren V Wood
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Levels of circulating tumor cells (CTCs) have been associated with overall survival (OS) in metastatic breast [[1][1]] and prostate cancer [[2][2]]. Here we report the preliminary associations between CTCs and OS in subjects receiving an autologous adenoviral transduced dendritic
Double Vs Single Autologous Stem Cell Transplantation After Bortezomib-Based Induction Regimens For Multiple Myeloma: An Integrated Analysis Of Patient-Level Data From Phase European III Studies
Authors: Michele Cavo, Hans Salwender, Laura Rosiñol, Philippe Moreau, Maria Teresa Petrucci, Igor Wolgang Blau, Joan Bladé, Michel Attal, Francesca Patriarca, Katja Weisel, Jesus F San Miguel, Herve Avet-Loiseau, Nicoletta Testoni, Michael Pfreundschuh, Juan Jose Lahuerta, Thierry Facon, Lucia Pantani, Christof Scheid, Norma Gutierrez, Gerald Marit, Antonio Palumbo, Maria Luisa Martin, Denis Caillot, Hartmut Goldschmidt
Journal: Blood (2013)
Enhanced tumor-infiltrating lymphocytes (eTIL) for cellular therapy of patients with pancreatic cancer or glioblastoma
Authors: Qingda Meng, Zhenjiang Liu, Markus Maeurer, Elena Rangelova, Aditya Ambati, Thomas Poiret, Lalit Rane, Shanshan Xie, Bartek Jiri, Caroline Verbeke, Oscar Persson, Matthias Löhr, Ralf Segersvärd, Ernest Dodoo
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts The generation of T lymphocytes with specific reactivity against autologous tumor cells is a prerequisite for effective targeted cellular therapies. We established a protocol for tumor infiltrating lymphocytes (TILs) cultures from small biopsies or surgically resected material
miR-34a Silences c-SRC to Attenuate Tumor Growth in Triple-Negative Breast Cancer
Authors: Brian D. Adams, Vikram B. Wali, Christopher J. Cheng, Sachi Inukai, Carmen J. Booth, Seema Agarwal, David L. Rimm, Balázs Győrffy, Libero Santarpia, Lajos Pusztai, W. Mark Saltzman, Frank J. Slack
Journal: Cancer Research (2015)

Triple-negative breast cancer (TNBC) is an aggressive subtype with no clinically proven biologically targeted treatment options. The molecular heterogeneity of TNBC and lack of high frequency driver mutations other than TP53 have hindered the development of new and effective therapies that significantly improve patient outcomes. miRNAs, global regulators of survival and proliferation pathways important in tumor development and maintenance, are becoming promising therapeutic agents. We performed miRNA-profiling studies in different TNBC subtypes to identify miRNAs that significantly contribute to disease progression. We found that miR-34a was lost in TNBC, specifically within mesenchymal and mesenchymal stem cell-like subtypes, whereas expression of miR-34a targets was significantly enriched. Furthermore, restoration of miR-34a in cell lines representing these subtypes inhibited proliferation and invasion, activated senescence, and promoted sensitivity to dasatinib by targeting the proto-oncogene c-SRC. Notably, SRC depletion in TNBC cell lines phenocopied the effects of miR-34a reintroduction, whereas SRC overexpression rescued the antitumorigenic properties mediated by miR-34a. miR-34a levels also increased when cells were treated with c-SRC inhibitors, suggesting a negative feedback exists between miR-34a and c-SRC. Moreover, miR-34a administration significantly delayed tumor growth of subcutaneously and orthotopically implanted tumors in nude mice, and was accompanied by c-SRC downregulation. Finally, we found that miR-34a and SRC levels were inversely correlated in human tumor specimens. Together, our results demonstrate that miR-34a exerts potent antitumorigenic effects in vitro and in vivo and suggests that miR-34a replacement therapy, which is currently being tested in human clinical trials, represents a promising therapeutic strategy for TNBC.
In AL Amyloidosis, Both Oral Melphalan and Dexamethasone (Mel-Dex) and Risk-Adapted Cyclophosphamide, Thalidomide and Dexamethasone (CTD) Have Similar Efficacy as Upfront Treatment.
Authors: Simon DJ Gibbs, Julian D Gillmore, Prayman T Sattianayagam, Mark Offer, Helen J Lachmann, Philip N Hawkins, Ashutosh D Wechalekar
Journal: Blood (2009)
Induction of systemic and therapeutic antitumor immunity using intratumoral injection of bone-marrow derived dendritic cells genetically modified to express interleukin 12 combined with anti-CTLA-4 antibody
Authors: Marimo Sato-Matsushita, Yoshihiro Hayakawa, Asuka Asami, Setsuko Nakayama, Hideaki Tahara
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts We have been involved in the development of cancer immunotherapy using dendritic cells (DCs) manipulated to induce better immune responses. Our strategies include the usage of the agent to induce desirable maturation of DCs in culture and the genetic modification of DCs to have
Study questions value of screening for fungal nail infections before starting treatment
Authors: Zosia Kmietowicz
Journal: BMJ (2015)

It is more cost effective to treat all suspected cases of nail fungus with oral terbinafine without first performing any diagnostic tests than obtaining laboratory confirmation, an analysis has found.

The US researchers said that guidelines encouraged healthcare professionals to seek confirmatory testing before starting systemic therapy for fungal nail infections. In the United Kingdom the National Institute for Health and Care Excellence also advises doctors to confirm the diagnosis with positive microscopy or positive culture before starting treatment.

Studies from the 1990s concluded that this approach was cost effective, but there has …
Dose-Escalated Stereotactic Body Radiotherapy (SBRT) as a Salvage Treatment for Two Cases with Relapsed Peripheral Lung Cancer After Initial SBRT
Authors: Shuichi Nishimura, Atsuya Takeda, Naoko Sanuki, Sachiko Yoshida, Naoyuki Shigematsu
Journal: Journal of Thoracic Oncology (2015)