tbuckley/cabot-search huggingface dataset:
P17 Respiratory impact of diabetes mellitus in people without a primary diagnosis of chronic lung disease: Abstract P17 Table 1
Authors: S Ruickbie, A Prasad, PW Jones, EH Baker
Journal: Thorax (2015)

<h3>Introduction</h3> In the UK, around 3 million people currently have a diagnosis of diabetes mellitus and the prevalence is increasing rapidly. Microvascular and macrovascular complications of diabetes are widely recognised, but the respiratory impact is less well understood. In people with chronic lung disease, diabetes mellitus is associated with worse lung function, impaired health status and more frequent exacerbations (Kinney <i>et al</i>. Diabetes Care. 2014;37:389–95). The aim of our study was to determine the respiratory impact of diabetes in people without a primary diagnosis of chronic lung disease. <h3>Methods</h3> Unselected patients attending for elective coronary angiography March–July 2015 were invited to take part in a prospective observational study (primary aim to investigate the association between coronary atheroma and airflow obstruction). Participants underwent clinical assessment and spirometry prior to the procedure. <h3>Results</h3> 250 of 294 (85%) people approached took part. Seventy five (30%) had diabetes mellitus. People with diabetes were of similar age and gender to those without diabetes, but had greater body mass index, central adiposity, blood glucose and HbA<sub>1c</sub> (Table 1). Despite no differences in history of smoking or respiratory illness (Table 1), people with diabetes had significantly lower forced vital capacity (FVC) and higher forced expiratory volume (FEV<sub>1</sub>): FVC ratio than those without diabetes. After adjustment for age, gender, body mass index, waist: hip ratio and smoking history, diabetes was an independent predictor of FEV<sub>1</sub>: FVC (partial eta<sup>2</sup> 0.03, p = 0.007), but not FVC. People with diabetes had more respiratory symptoms (Table 1). They were more likely to give a history of recurrent chest infections (diabetes 14(19%); no diabetes 11(6%), p = 0.004) and reported more chest infections (diabetes 0.6 ± 1.6; no diabetes 0.2 ± 0.9, p = 0.007) in the past year. After adjustment for age, waist: hip ratio, body mass index, smoking, FEV<sub>1</sub>: FVC and co-existing respiratory disease, diabetes was an independent predictor of recurrent chest infections (odds ratio 2.81 (95% confidence intervals 1.04–7.73), p = 0.045). <h3>Conclusions</h3> Diabetes mellitus is associated with worse lung function, increased respiratory symptoms and more frequent chest infections, independent of smoking and prior respiratory illness. The burden of diabetes-associated respiratory disease on patients and the NHS is likely to increase as diabetes becomes more prevalent.
Safety and efficacy of Ad5/3-D24-GMCSF, a serotype 5/3 chimeric oncolytic adenovirus expressing granulocyte macrophage colony-stimulating factor (GM-CSF), in treatment of metastatic and refractory solid tumors.
Authors: A. Hemminki, S. Pesonen, A. Koski, V. Cerullo, S. Escutenaire, E. Haavisto, L. Kangasniemi, P. Simula, T. K. Joensuu
Journal: Journal of Clinical Oncology (2010)

e13506 Background: Oncolytic viruses are emerging as promising tools for treating cancer refractory to current therapies. Redirecting and augmenting the antitumor immune response is a promising way to enhance the antitumor effects of oncolytic adenoviral therapy. Granulocyte-macrophage colony stimulating factor (GMCSF) can mediate antitumor effects by recruiting natural killer cells and by induction of tumor-specific CD8+ cytotoxic T-lymphocytes. Oncolytic killing can produce a potent costimulatory danger signal and release of tumor epitopes for APC sampling. Serotype 5 viruses are commonly used in cancer gene therapy. However, expression of the adenovirus receptor CAR might be variable in many advanced tumors and preclinical data has demonstrated an advantage for replacing the Ad5 knob with the Ad3 knob. Methods: A 5/3 capsid modified oncolytic adenovirus coding for GMCSF was engineered and 21 patients with advanced solid tumors, refractory to standard therapies, were treated and followed for adverse events, evidence of biological activity and clinical benefit. Data on neutralizing antibody, cytokine, and CD8+ lymphocyte responses was also collected. Induction of tumor and adenovirus specific immunity was demonstrated with ELISPOT and pentamer analysis. Results: Overall, all patients experienced grade 1-2 adverse events including fever, fatigue, and flu-like symptoms, but only a few grade 3 and no grade 4-5 adverse events were reported. Evidence of biological activity of the virus was seen in 13/21 (62%) patients and 8/12 (67%) showed objective clinical benefit as evaluated with RECIST. Virus replication was seen in 80% of patients for up to 58 days. Pretreatment analysis of tumors seemed able to predict subsequent clinical benefit. Conclusions: Ad5/3-D24-GMCSF seems safe and effective for further clinical testing. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Oncos Therapeutics Inc.
Very Long Term Clinical Outcomes of Patients with Coronary Bifurcation Lesions Treated with the Biolimus A9 Coated Dedicated Axxess Stent: Results from the Prospective, Multicenter AXXESS Plus Trial (Final Report of the Study)
Authors: Eberhard Grube, Franz-Josef Neumann, Stefan Verheye, Alexandre Abizaid, Dougal McClean, Karl E Hauptmann, Iain Simpson, Philip MacCarthy, Christophe Dubois, Ralf Mueller
Journal: Journal of the American College of Cardiology (2011)
The effects of growing up on a farm on adult lung function and allergic phenotypes: an international population-based study
Authors: B Campbell, C Raherison, C J Lodge, A J Lowe, T Gislason, J Heinrich, J Sunyer, F Gómez Real, D Norbäck, M C Matheson, M Wjst, J Dratva, R de Marco, D Jarvis, V Schlünssen, C Janson, B Leynaert, C Svanes, S C Dharmage
Journal: Thorax (2016)

<h3>Rationale</h3> Evidence has suggested that exposure to environmental or microbial biodiversity in early life may impact subsequent lung function and allergic disease risk. <h3>Objectives</h3> To investigate the influence of childhood living environment and biodiversity indicators on atopy, asthma and lung function in adulthood. <h3>Methods and measurements</h3> The European Community Respiratory Health Survey II investigated ∼10 201 participants aged 26–54 years from 14 countries, including participants9 place of upbringing (farm, rural environment or inner city) before age 5 years. A 'biodiversity score' was created based on childhood exposure to cats, dogs, day care, bedroom sharing and older siblings. Associations with lung function, bronchial hyper-responsiveness (BHR), allergic sensitisation, asthma and rhinitis were analysed. <h3>Main results</h3> As compared with a city upbringing, those with early-life farm exposure had less atopic sensitisation (adjusted OR 0.46, 95% CI 0.37 to 0.58), atopic BHR (0.54 (0.35 to 0.83)), atopic asthma (0.47 (0.28 to 0.81)) and atopic rhinitis (0.43 (0.32 to 0.57)), but not non-atopic outcomes. Less pronounced protective effects were observed for rural environment exposures. Women with a farm upbringing had higher FEV<sub>1</sub> (adjusted difference 110 mL (64 to 157)), independent of sensitisation and asthma. In an inner city environment, a higher biodiversity score was related to less allergic sensitisation. <h3>Conclusions</h3> This is the first study to report beneficial effects of growing up on a farm on adult FEV<sub>1</sub>. Our study confirmed the beneficial effects of early farm life on sensitisation, asthma and rhinitis, and found a similar association for BHR. In persons with an urban upbringing, a higher biodiversity score predicted less allergic sensitisation, but to a lesser magnitude than a childhood farm environment.
Five minutes with . . . John Ioannidis
Authors: Susan Mayor
Journal: BMJ (2016)

The Stanford University professor talks about the problems with meta-analyses

“We have an epidemic of deeply flawed meta-analyses, with the number published each year having increased by more than 2600% over the past 20 years, compared with only 50% for research studies of all types listed on PubMed.1

“There is now massive production of unnecessary, misleading, and conflicted systematic reviews and meta-analyses. While these designs represent the highest level of evidence, they are often massively misused, and …
Avelumab (MSB0010718C), an anti-PD-L1 antibody, in advanced NSCLC patients: A phase 1b, open-label expansion trial in patients progressing after platinum-based chemotherapy.
Authors: James L. Gulley, David Spigel, Karen Kelly, Jason Claud Chandler, Arun Rajan, Raffit Hassan, Deborah Jean Lee Wong, Joseph Leach, William Jeffery Edenfield, Ding Wang, Nandagopal Vrindavanam, Glen J. Weiss, Jayne S. Gurtler, Hans Juergen Grote, Anja von Heydebreck, Kevin M. Chin, Nicholas Iannotti
Journal: Journal of Clinical Oncology (2015)

8034 Background: The programmed death-1 receptor (PD-1) and its ligand (PD-L1) are key therapeutic targets in the reactivation of the immune response against cancer. Avelumab* (MSB0010718C) is a fully human anti-PD-L1 IgG1 antibody being investigated in clinical trials. We report safety and clinical activity in patients (pts) with advanced NSCLC progressing after platinum-based chemotherapy (NCT01772004). Methods: Pts were treated with avelumab at 10 mg/kg Q2W until progression, confirmed complete response (CR), or toxicity. A prespecified analysis of 184 pts with ≥ 3 months follow-up (range 3-13) was performed. Tumors were assessed every 6 weeks (w) (RECIST 1.1) and unconfirmed best overall response (BOR) was evaluated. Tumor PD-L1 expression was assessed by immunohistochemistry. Results: Median age was 65y (range 31-83) and ECOG PS was 0 (30%) or 1 (70%). Histology was adenocarcinoma (62%), squamous cell carcinoma (29%), or other (9%). Any grade drug-related treatment-emergent adverse events (TEAEs) occurred in 139 (75.5%) pts; the most common ( > 5%) were fatigue, nausea, infusion-related reactions (IRRs), chills, decreased appetite, and diarrhea. Drug-related grade ≥ 3 TEAEs occurred in 22 (12%) pts, including 4 IRRs. Drug-related deaths were reported (n = 3; radiation pneumonitis, acute respiratory failure, and disease progression). Objective responses (OR) were observed in 22 (12%) pts (95% CI: 7.6, 17.5; 1 CR, 21 partial responses; 18 were ongoing at data cutoff). BOR of stable disease was observed in 70 pts (38%). Median progression-free survival (PFS) was 11.6 w (95% CI: 8.4, 12.1) and the PFS rate at 24 w was 25.4% (95% CI: 18.3, 33.2). Tumors were PD-L1(+) in 86% of evaluable pts (1% cutoff). The ORR in PD-L1(+) pts (n = 118) was 14.4% and 10.0% in PD-L1(-) pts (n = 20). Median PFS in PD-L1(+) pts was 11.7 w vs 5.9 w in PD-L1(-) pts. Conclusions: In pts with previously treated NSCLC, avelumab was administered safely with a toxicity profile similar to other anti-PD-1/anti-PD-L1 agents. A trend of greater activity in pts with PD-L1(+) tumors was observed. A randomized phase 3 trial of avelumab in pts with advanced NSCLC is planned. *Proposed INN. Clinical trial information: NCT01772004.
Anti-angiogenesis through noninvasive to minimally invasive intraocular delivery of the peptide CC12 identified by in vivo-directed evolution
Authors: Chong Chen, Kun Liu, Yupeng Xu, Pengwei Zhang, Yan Suo, Yi Lu, Wenyuan Zhang, Li Su, Qing Gu, Huamao Wang, Jianren Gu, Zonghai Li, Xun Xu
Journal: Biomaterials (2016)
P1339 : Evaluating the efficacy and safety of everolimus with reduced tacrolimus versus standard tacrolimus in living donor liver transplant recipients: H2307 study design
Authors: C. Sips, K.S. Suh, J.W. Joh, T. Yoshizumi, W.C. Lee, Y. Genyk, E.-D. Martzloff, Z. Wang, P. Lopez, D. Grant
Journal: Journal of Hepatology (2015)
Artificially Sweetened Beverage Consumption During Pregnancy and Infant Body Mass Index—Reply
Authors: Meghan B. Azad, Russell J. de Souza, Atul K. Sharma
Journal: JAMA Pediatrics (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Understanding disease mechanisms at the nanoscale: endothelial apoptosis and microparticles in COPD
Authors: Tom Wilkinson
Journal: Thorax (2016)

The clinical burden of COPD remains a global health challenge that is not being met by current preventive and therapeutic strategies.1 For decades, the key features of this heterogeneous condition have been studied and the associations between airways disease, emphysema, systemic illness and tobacco smoking have been explored. Despite significant advances in our understanding of the aetiology of important clinical aspects of disease including the heterogeneity of airway inflammation2 and the pathogenesis of exacerbations,3 there remain significant gaps in our understanding of the mechanisms underlying key facets of the condition including the origins of emphysema.

A number of potential mechanisms of disease have been proposed to explain the progressive loss of lung parenchyma in response to tobacco and biomass smoke exposure.4 Focus on protease imbalance and neutrophilic inflammation5 on one hand and T-cell-mediated pathology on another6 have offered some insights into contributory mechanisms but to date have failed to offer a route to disease modifying therapy or even convincing biomarkers of disease progression.

Furthermore, it is increasingly apparent that COPD is both a pulmonary and systemic condition, with a significant contribution to the associated morbidity and mortality driven by an increased incidence and severity of cardiovascular disease.7 It has been recognised that endothelial pathology is a key component of COPD, both in the manifestation of a systemic disease process and in the development of discrete lung pathology …
P0132 : External validation of the CLIF-SOFA in cirrhotic patients admitted to intensive care units (ICUS): A meta-analysis
Authors: D. Weil, V. Di Martino, E. Levesque, M. McPhail, R. Cavallazzi, E. Theocharidou, E. Cholongitas, A. Galbois, H.-C. Pan, C. Karvellas, B. Sauneuf, R. Robert, J. Fichet, G. Piton, G. Capellier, T. Thévenot
Journal: Journal of Hepatology (2015)
Novel function of FAXDC2 in megakaryopoiesis
Authors: Q Jin, Y Ren, M Wang, P K Suraneni, D Li, J D Crispino, J Fan, Z Huang
Journal: Blood Cancer Journal (2016)

FAXDC2 (fatty acid hydroxylase domain containing 2) is a member of the fatty acid hydroxylase superfamily. Given the important role of fatty acids in megakaryocytes, we have studied the role of this gene in the development of this lineage. Here we show that the expression of FAXDC2 is constantly elevated during megakaryocyte maturation. In contrast, FAXDC2 is significantly downregulated in acute myeloid leukemia and acute megakaryoblastic leukemia. Moreover, FAXDC2 overexpression promotes the differentiation of megakaryocytic cell lines and primary cells, whereas its knockdown disrupts their maturation. Mechanism study shows that FAXDC2 overexpression enhances extracellular signal-regulated kinase (ERK) signaling and increases RUNX1 (Runt-related transcription factor 1) expression. FAXDC2 also restores megakaryocytic differentiation in cells exposed to an ERK inhibitor or those expressing a dominant negative form of RUNX1. Finally, FAXDC2 overexpression leads to an increase in sphingolipid GM3 synthase, suggesting a potential role of FAXDC2 in lipid metabolism that increases ERK signaling and facilitates megakaryocyte differentiation. Together, these results show that FAXDC2 plays a novel role in development of megakaryocytes and its dysregulation may contribute to abnormal hematopoietic cell development in leukemia.
Mir-15a/16-1 Cluster Is Frequently Deleted In Primary Hodgkin Lymphoma and Modulates Multiple Survival Pathways Including AP-1
Authors: Bjoern Chapuy, Michael R Green, Jun Lu, Stefano Monti, Yansheng Hao, Kelly T Yeda, Scott J Rodig, Treeve Currie, Kunihiko Takeyama, Todd R Golub, Jeffery Kutok, Margaret A. Shipp
Journal: Blood (2010)
Incorporation of Bortezomib Into Frontline Treatment of Multiple Myeloma According to Risk Stratification Shifts the Most Significant Prognostic Indicator From Cytogenetics to the Quality of Induction Response
Authors: Daryl Tan, Bernard K.C Yap, Lionel K.Y See, Grace Kam, Colin Phipps Diong, Yuh Shan Lee, Dawn Mya, William Hwang, Yeow Tee Goh
Journal: Blood (2010)
Passions in Every Room
Authors: Michael Wynn
Journal: JAMA (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
HER receptor signaling confers resistance to IGF-1R targeted therapy
Authors: P. Haluska, J. M. Carboni, C. Yu, C. Ten Eyck, R. M. Attar, Y. W. Asmann, M. Sagar, T. W. Wong, M. M. Gottardis, C. E. Erlichman
Journal: Journal of Clinical Oncology (2008)

14510 Background: Signaling through the insulin-like growth factor 1 receptor (IGF-1R) has been implicated in the resistance to a number of clinically relevant anti-cancer agents, including inhibitors of the HER family of receptors. Preliminary data suggests that co-inhibition of IGF and HER pathways may improve the efficacy of targeting these pathways individually. Methods: Five ovarian cancer cell line where treated with the IGF-1R inhibitor, BMS-536924 (924) and/or the panHER inhibitor, BMS-599626. Activity was assessed by proliferation and apoptotic assays. Protein expression/activation was assessed by western blotting. Stably transfected MCF-7 variants were generated to contain either the empty expression vector (M/-), EGFR/HER1 (M/H1) or HER2 (M/H2). MCF-7R4 cells (R4) are a clonal isolate of MCF-7 cells passaged in high concentration of the IGF-1R inhibitor, BMS-554417. The expression profile of R4 cells were compared to MCF-7 using Affymetrix GeneChip Human Genome U133 Plus 2.0 Arrays. Results: IGF-1R and HER receptor co-inhibition had synergistic anti- proliferative activity in all 5 ovarian cell lines investigated. The mechanism of this synergy was enhancement of apoptosis. Evidence of HER receptor activation was observed in all cell lines in response to IGF-1R inhibition. M/H1 and M/H2 became highly resistant to the effects of 924 in the presence of EGF and heregulin, respectively. R4 cells are cross-resistant to 924 and other IGF-1R inhibitors. Compared to MCF-7 cells, HER2 and HER3 are upregulated and overactivated in R4 cells. Additionally, R4 cells have altered expression of IGFBP-5, -6 and IRS-1, -2. Conclusions: Co-inhibition of IGF-1R and HER receptors leads to synergistic activity in all tested ovarian cancer cell lines, all of which exhibited evidence of crosstalk. Activated EGFR or HER2 appears sufficient for resistance to IGF-1R inhibition. As IGF-1R inhibition strategies enter the clinic, HER receptors status and consideration of co-inhibition will be important for their development. Several IGF-1 system related proteins, including IGFBP-5 and 6 may have utility in predicting response to IGF-1R targeted therapy. Supported by the ASCO Young Investigator Award, Mayo Clinic Breast SPORE (CA116201–01) and K12 program (CA090628–05). Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb, Pfizer Oncology Bristol-Myers Squibb
TGFβ1-Mediated SMAD3 Enhances PD-1 Expression on Antigen-Specific T Cells in Cancer
Authors: Benjamin V. Park, Zachary T. Freeman, Ali Ghasemzadeh, Michael A. Chattergoon, Alleluiah Rutebemberwa, Jordana Steigner, Matthew E. Winter, Thanh V. Huynh, Suzanne M. Sebald, Se-Jin Lee, Fan Pan, Drew M. Pardoll, Andrea L. Cox
Journal: Cancer Discovery (2016)

Abstract Programmed death-1 (PD-1) is a coinhibitory receptor that downregulates the activity of tumor-infiltrating lymphocytes (TIL) in cancer and of virus-specific T cells in chronic infection. The molecular mechanisms driving high PD-1 expression on TILs have not been fully investigated. We demonstrate that TGFβ1 enhances antigen-induced PD-1 expression through SMAD3-dependent, SMAD2-independent transcriptional activation in T cells in vitro and in TILs in vivo. The PD-1hi subset seen in CD8+ TILs is absent in Smad3-deficient tumor-specific CD8+ TILs, resulting in enhanced cytokine production by TILs and in draining lymph nodes and antitumor activity. In addition to TGFβ1′s previously known effects on T-cell function, our findings suggest that TGFβ1 mediates T-cell suppression via PD-1 upregulation in the tumor microenvironment (TME). They highlight bidirectional cross-talk between effector TILs and TGFβ-producing cells that upregulates multiple components of the PD-1 signaling pathway to inhibit antitumor immunity. Significance: Engagement of the coinhibitory receptor PD-1 or its ligand, PD-L1, dramatically inhibits the antitumor function of TILs within the TME. Our findings represent a novel immunosuppressive function of TGFβ and demonstrate that TGFβ1 allows tumors to evade host immune responses in part through enhanced SMAD3-mediated PD-1 expression on TILs. Cancer Discov; 6(12); 1366–81. ©2016 AACR. This article is highlighted in the In This Issue feature, p. 1293