tbuckley/cabot-search huggingface dataset:
Diabetes is rising in OECD countries, report warns
Authors: J. Wise
Journal: BMJ (2015)

Deaths from cardiovascular disease have fallen by over 60% in the past 50 years in the Organisation for Economic Cooperation and Development (OECD) member states, but rising levels of obesity and diabetes threaten the prospects of further improvement, a new report warns.

Cardiovascular Disease and Diabetes: Policies for Better Health and Quality of Care 1 said that cardiovascular disease remains the leading cause of death in OECD countries. The OECD comprises 34 countries including the United States, Canada, Australia, Japan, Korea, Mexico, Chile, and a number of European countries.

About 85 million people have diabetes in OECD countries, representing around 7% of people aged 20-79. However, …
Small Molecule Modulators of <scp>K</scp>eap1‐<scp>N</scp>rf2‐<scp>ARE</scp> Pathway as Potential Preventive and Therapeutic Agents
Authors: Sadagopan Magesh, Yu Chen, Longqin Hu
Journal: Medicinal Research Reviews (2012)

Abstract K elch‐like ECH ‐associated protein 1 ( K eap1)‐nuclear factor erythroid 2‐related factor 2 ( N rf2)‐antioxidant response elements ( ARE ) pathway represents one of the most important cellular defense mechanisms against oxidative stress and xenobiotic damage. Activation of N rf2 signaling induces the transcriptional regulation of ARE‐dependent expression of various detoxifying and antioxidant defense enzymes and proteins. Keap1‐Nrf2‐ARE signaling has become an attractive target for the prevention and treatment of oxidative stress‐related diseases and conditions including cancer, neurodegenerative, cardiovascular, metabolic, and inflammatory diseases. Over the last few decades, numerous N rf2 inducers have been developed and some of them are currently undergoing clinical trials. Recently, overactivation of N rf2 has been implicated in cancer progression as well as in drug resistance to cancer chemotherapy. Thus, N rf2 inhibitors could potentially be used to improve the effectiveness of cancer therapy. Herein, we review the signaling mechanism of K eap1‐ N rf2‐ ARE pathway, its disease relevance, and currently known classes of small molecule modulators. We also discuss several aspects of K eap1– N rf2 interaction, N rf2‐based peptide inhibitor design, and the screening assays currently used for the discovery of direct inhibitors of K eap1‐ N rf2 interaction. © 2012 Wiley Periodicals, Inc. Med Res Rev., 32, No. 4, 687‐726, 2012
Multiplexed IgE determination in relation to asthma, exhaled NO and bronchial reactivity: Results from a population based survey
Authors: Antonios Patelis, Maria Gunnbjörnsdottir, Andrei Malinovschi, Per Mattsson, Annica Önell, Marieann Högman, Kjell Alving, Christer Janson
Journal: European Respiratory Journal (2011)

Background: IgE sensitization is an important risk factor for the development and management of asthma. The aim of this study was to investigate the IgE antibody profile for a broad spectrum of allergen molecules in asthmatic patients.

Methods: Participants from the European Community Respiratory Health Survey II (n=467) were tested with ImmunoCAP ISAC against 103 allergen molecules. Bronchial responsiveness was measured with methacholine test and bronchial inflammation with FENO0.05.

Results: A total of 50.7% of the controls and 80.2% of the asthmatics were sensitized against at least one food, pollen, furry animals, mould or latex allergen (p<0.0001). Asthma and increased FENO0.05 were independently related to IgE against pollen and perennial inhaled allergens, while bronchial responsiveness was only independently associated with perennial allergens. Sensitization against perennial allergens was associated with asthma (OR 3.6 CI 95% 1.2-10.6) and bronchial responsiveness. Sensitization to food allergens was related to asthma and increased FENO0.05 only if IgE against pollen and/or perennial allergens were present. Simultaneous sensitization to perennial, pollen and food allergens involves the highest risk for asthma (OR 14.7 CI 95% 7.1-30.5), bronchial inflammation and responsiveness.

Conclusion: FENO0.05 values, bronchial responsiveness and risk for asthma increase with multiple sensitization to different allergen groups. IgE against food allergens increases the risk for asthma and increased FENO0.05 in subjects with simultaneous sensitization to pollen and/or perennial allergens.
Abstract IA12: Correlating cancer heterogeneity to treatment response and relapse
Authors: Elli Papaemmanuil
Journal: Clinical Cancer Research (2015)

Abstract Systematic sequencing screens of hundreds of cancer genomes has delivered a near complete catalogue of somatic mutations in the coding genome that drive oncogenic transformation across a diverse range of tumor types. The picture that is emerging is one of extensive genomic diversity and clonal complexity. Our recent work in MDS has shown that the underlying genomic architecture is predominantly characterized by infrequently mutated genes (&amp;lt;5% of patient samples), specific gene-gene interactions and a structured order of mutation acquisition, implicating mutations in RNA splicing as early initiating events followed by secondary mutations in epigenetic modifiers and transcriptional regulators. The enrichment for infrequently mutated genes and complex secondary interactions impose significant challenges in defining prognostic and predictive biomarkers of patient outcome and therapeutic response. Single gene studies are not entirely representative of the disease pathophysiology and certainly do not account for the epistatic or modifying effects conferred by the composite underlying genetic architecture. Detailed investigations on well-annotated patient cohorts pre-, during and post- treatment support the definition of predictive signatures of response and studies investigating changes in clonal dynamics using sequential samples during therapy are offering important new avenues in understanding the underlying biology of chemo sensitivity as well as resistance. Citation Format: Elli Papaemmanuil. Correlating cancer heterogeneity to treatment response and relapse. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Drug Sensitivity and Resistance: Improving Cancer Therapy; Jun 18-21, 2014; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(4 Suppl): Abstract nr IA12.
Transforming growth factor-β1 is a potent inhibitor of secretory leukoprotease inhibitor expression in a bronchial epithelial cell line
Authors: F. Jaumann, A. Elssner, G Mazur, S Dobmann, C Vogelmeier, None for the Munich Lung Transplant Group
Journal: European Respiratory Journal (2000)

Obliterative bronchiolitis (OB) is the major long-term complication following lung and heart-lung transplantation. In bronchoalveolar lavage fluid samples obtained from patients suffering from OB, a marked increase in the number of neutrophils and elevated expression of transforming growth factor (TGF)-beta1 had been found. The goal of the study was to evaluate whether TGF-beta1 is capable of interfering with the expression of the secretory leukoprotease inhibitor (SLPI), the dominating defence of the conducting airways against neutrophil elastase (NE). The authors analysed the effects of TGF-beta1 on gene expression and protein release of SLPI by cultured human bronchial epithelial (BEAS-2B) cells. SLPI protein levels in the supernatants were quantified with a specific enzyme-linked immunosorbent assay; SLPI messenger ribonucleic acid (mRNA) levels were measured by reverse transcriptase polymerase chain reaction. Incubation with TGF-beta1 induced a marked decrease in SLPI protein levels (1 ng x mL(-1) TGF-beta1: stimulation index (SI; protein: relation to SLPI protein release of resting cells)=0.56; 10 ng x mL(-1) TGF-beta1: SI=0.48; 50 ng x mL(-1) TGF-beta1: SI=0.37, p&lt;0.01 each) and mRNA expression (1 ng x mL(-1) TGF-beta1: SI (SI mRNA: relation to SLPI mRNA expression of resting cells)=0.46; 10 ng x mL(-1) TGF-beta1: SI=0.31; 50 ng x mL(-1) TGF-beta1: SI=0.18, p&lt;0.01 each) in a dose dependent fashion. Simultaneous incubation of BEAS-2B cells with TGF-beta1 and NE also caused a significant reduction in SLPI synthesis (10 ng x mL(-1) TGF-beta1 + 7.5 U x mL(-1) NE: mRNA SI=0.61, p&lt;0.05; protein SI=0.65, p&lt;0.05; 50 ng x mL(-1) TGF-beta1 + 7.5 U x mL(-1) NE: mRNASI=0.52, p&lt;0.05; protein SI=0.58, p&lt;0.05; 10 ng x mL(-1) TGF-beta1: mRNA SI=0.33, p&lt;0.01; protein SI=0.38, p&lt;0.01). In conclusion, the data suggest that the coincidence of neutrophilia and upregulation of transforming growth factor-beta1 in obliterative bronchiolitis may lead to uninhibited neutrophil elastase activity by downregulation of secretory leukoprotease inhibitor, with the consequence of ongoing injury to the epithelium.
Distinct Roles For Hepcidin and Interleukin 6 In The Recovery From Anemia Following Administration Of Heat-Killed Brucella Abortus
Authors: Sara Gardenghi, Thomas M. Renaud, Alessandra Meloni, Carla Casu, Bart J. Crielaard, Laura M. Bystrom, Noa Greenberg, Barbra J. Sasu, Keegan S. Cooke, Stefano Rivella
Journal: Blood (2013)
Histological regression in primary melanoma: not a predictor of sentinel lymph node metastasis in a cohort of 397 patients
Authors: Y. Socrier, V. Lauwers-Cances, L. Lamant, I. Garrido, F. Lauwers, R. Lopez, P. Rochaix, C. Chevreau, P. Payoux, R. Viraben, C. Paul, N. Meyer
Journal: British Journal of Dermatology (2009)

Background Regression has been proposed as a potential marker of dissemination in thin melanomas. Previous studies have shown conflicting results. Objective To determine if regression in melanoma is associated with an increased risk of sentinel lymph node (SLN) metastasis. Methods A cohort analysis was conducted. Data on all patients were collected on a standardized case report form during 10 years. A total of 397 consecutive patients with melanoma who underwent a SLN biopsy were analysed. All cases of melanoma and SLN biopsies were examined by the same two pathologists. Differences between melanomas with and without SLN metastasis were compared using Fisher’s exact test or the two‐sample t‐test and the χ2 test. Multivariable logistic regression was used to adjust for possible confounding factors. Results We analysed 397 patients (411 melanomas) who underwent a SLN biopsy. The median Breslow index was 1·8 mm (interquartile range 1·1–3). Regression was observed in 23% (n =94). SLN metastases were observed in 26% (n =106). The frequency of SLN metastasis was 16% in melanomas with regression and 29% without regression (P =0·012). The adjusted odds ratio (OR) for regressive melanoma was 0·9 [95% confidence interval (CI) 0·4–1·9; P =0·777]. The risk of SLN metastasis was increased in melanoma cases with a Breslow index from 1·5 to < 2·0 mm (adjusted OR 3·1; 95% CI 1·4–7·1; P =0·006) and ≥ 2·0 mm (adjusted OR 3·5; 95% CI 1·7–7·4; P =0·001) and ulceration of the melanoma (adjusted OR 1·8; 95% CI 1·1–3·2; P =0·03). Conclusion Regression is not an independent predictor of the risk of SLN metastasis in melanoma.
Proceedings of the British Thoracic Society. 1986 winter meeting. 11-12 December 1986, London. Abstracts.
Authors: A. Fennerty, H. Shetty, D. Payton, Philip Alexander Routledge, Ian A. Campbell
Journal: Thorax (1987)

Relationships between respiratory symptoms and exposure to inspirable dust, measured by personal sampling, have been investigated in 2153 workers at 15 mills manufacturing woollen cloth and carpet yarns.We designed a detailed questionnaire to establish a broad range of symptoms and their possible relationship to occupation, current and cumulative dust exposure.The questionnaire was translated into Urdu for use on employees of Asian origin.Symptom prevalences in the population were: chronic bronchitis, 9%; wheeze, 31%/; grade three breathlessness, 10%0; persistent rhinitis, 18%; persistent conjunctivitis, 10%; persistent chills, 2%; 10 or more nosebleeds in past year, 2%.Many of these symptoms were related to current dust exposure, once age, sex, smoking habit and ethnic group had been allowed for.Nine per cent of the workforce were exposed on average to inspirable dust levels greater than 10 mg/m3, the nuisance dust standard, the relative risk of symptoms at this concentration ranging from 1.3 to 1.6 times that of unexposed workers.The predicted prevalence of chronic bronchitis, for example, rose from 4% for a 40 year old, European, non-smoking, male, non-process worker to 8% for the quivalent worker exposed to 25 mg/m3, the 95th percentile dust concentration.Dust control strategies can be based on these results.
Long-Term Outcomes After Stenting of Bifurcation Lesions With the “Crush” Technique
Authors: Angela Hoye, Ioannis Iakovou, Lei Ge, Carlos A.G. van Mieghem, Andrew T.L. Ong, John Cosgrave, Giuseppe M. Sangiorgi, Flavio Airoldi, Matteo Montorfano, Iassen Michev, Alaide Chieffo, Mauro Carlino, Nicola Corvaja, Jiro Aoki, Gaston A. Rodriguez Granillo, Marco Valgimigli, Georgios Sianos, Willem J. van der Giessen, Pim J. de Feyter, Ron T. van Domburg, Patrick W. Serruys, Antonio Colombo
Journal: Journal of the American College of Cardiology (2006)
Mesothelioma in north east London
Authors: Elizabeth Hadley, Terence O'Shaughnessy, Fiona Breen, Michael Apps
Journal: European Respiratory Journal (2011)

The North East London Cancer Network (NELCN) has the second highest incidence of mesothelioma in the UK. The 2010 ERS/ESTS malignant pleural mesothelioma guidelines have subjected the evidence to systematic review and it was felt that the network should audit its own service in 2009 & 2010.  There were 52 new cases of mesothelioma, data was obtained on 34. Of these patients 91% were pleural and 9% peritoneal. Over 90% was confirmed histologically. All patients were discussed in a multidiciplinary team meeting (MDT), 50% received chemotherapy. All patients who had a VATS biopsy had a surgical pleurodesis. At the end of the audit deadline 11/34 patients had died including all patients with sarcomatoid histology.  Lung cancer patients in the NELCN are known to present late with advanced disease, only 41% of these patients came through a respiratory specialist as a first port of call, and only 35% as urgent cancer referrals.  Chemotherapy was offered to 74% of patients, but only 50% had it. Most of those did not have chemotherapy because of poor performance status. However in two cases chemotherapy was delayed in order to wait for symptoms. The current ERS/ESTS evidence suggests that chemotherapy before symptom progression has a better outcome.  Port site radiotherapy was given to a third of patients, those who did not have chemotherapy. This is in line with the BTS 2007 statement.  The NELCN has a high case load of mesothelioma. Diagnostics are moving uniformly across the network towards early CT biopsy or VATs biopsy. Palliative surgical pleurodseis is common and chemotherapy is being offered to three quarters of patients. Mesothelioma MDTs are operational and assist in optimizing patient pathways.
The specialist of the discipline of general practice
Authors: I. Heath
Journal: BMJ (2000)

General practice p 354 

Over the past 50 years general practice has established itself not only as an academic discipline with its own curriculum, research base, and peer reviewed journals but also as the cornerstone of most national healthcare systems in Europe. In so doing, general practitioners have shown that the intellectual framework within which they operate is different from, complementary to, but no less demanding than that of specialists. General practitioners must achieve a working diagnostic and therapeutic knowledge across the reach of biomedical science and must be able to forge effective and continuing relationships with an enormous range of individual patients. They need to understand the processes by which illness is socially constructed within the patient's life, and they must mediate between the patient's subjective experience of illness and the scientific explanation.

The breadth and comprehensiveness of its endeavour has made general practice notoriously difficult to define. 1 On p 354 Olesen et al attempt a new definition that …
Effect of the ADAPT strategy on dormant CD133+ colon cancer stem cells (CSC) and molecular complete remission measured by peripheral blood mononuclear (PBMC) CD133 mRNA.
Authors: Edward H. Lin, Yu Xiazhen, Xi C He, Xifeng Wu, Yang Xie, Yanhong Deng, Guang Yang, Qiang Tian, Lingheng Li
Journal: Journal of Clinical Oncology (2012)

e14153 Background: The median survival for patients with unresectable metastatic colorectal cancer (CRC) is ~2 years with modern chemotherapy which yields only 5-10% complete responses (CR) including metastasectomy. Recurrences after CR are very common thanks to presence of dormant CSC that are best targeted by our proposed two-step ADAPT strategy: activate from dormancy and potentiate targeting. We examine this strategy in various CRC models and reviewed the impact on stemess including CD133 mRNA, a circulating CSC marker that predict colon cancer relapse. Methods: Different CRC models (in vitro and in vivo) were interrogated similar to clinical ADAPT treatment protocol using capecitabine (or 5FU) plus celecoxib. We also conducted IRB approved retrospective review of unresectable metastatic CRC patients treated ADAPT therapy and in those who also had PBMC CD133 mRNA measured. Results: Contrary to 5FU, which eliminates proliferating CRC cells via apoptosis but also stimulates stemness, celecoxib preferentially deplete CD133+ colon cells and exert potent stemness inhibition via rapid tumor necrosis by perturbing hypoxia and energy metabolism via CA-IX. Following response to first-line chemotherapy, ADAPT strategy plus radiation improved CR or near CR rate to 49/126 (40%) in unresectable CRC patients whose median survival had reached 92.7 months (95% CI, 53.5 months - not reached). Paradoxically, none surgical CR patients (n= 16) enjoyed 100% 5-year relapse free survival compared to 42% of surgical patients (p = 0.04). The PBMC CD133 mRNA in five long-term CR patients were 0.0024, 0.29, 0.5, 0.56, 2.96 respectively, all below previously reported cutoff value of 4.79 for recurrence and far below CD133 mRNA levels (28, 375, 3997, 15662, 83240) in none CR patients. Conclusions: ADAPT plus radiation preferentially targets colon CSC via hypoxia/CA-IX and improves clinical CR rate and molecular CR as measured by PBMC CD133 mRNA. We are actively interrogating the effects of ADAPT strategies in a phase II study funded by Gateway in CRC patients and in genetic CRC animal models.
DNA-PKcs-Mediated Transcriptional Regulation Drives Prostate Cancer Progression and Metastasis
Authors: Jonathan F. Goodwin, Vishal Kothari, Justin M. Drake, Shuang Zhao, Emanuela Dylgjeri, Jeffry L. Dean, Matthew J. Schiewer, Christopher McNair, Jennifer K. Jones, Alvaro Aytes, Michael S. Magee, Adam E. Snook, Ziqi Zhu, Robert B. Den, Ruth C. Birbe, Leonard G. Gomella, Nicholas A. Graham, Ajay A. Vashisht, James A. Wohlschlegel, Thomas G. Graeber, R. Jeffrey Karnes, Mandeep Takhar, Elai Davicioni, Scott A. Tomlins, Cory Abate-Shen, Nima Sharifi, Owen N. Witte, Felix Y. Feng, Karen E. Knudsen
Journal: Cancer Cell (2015)
Occurrence of extended-spectrum β-lactamase-producing Salmonella enterica in northern Spain with evidence of CTX-M-9 clonal spread among animals and humans
Authors: I. Riaño, M. García-Campello, Y. Sáenz, P. Álvarez, L. Vinué, M. Lantero, M.Á. Moreno, M. Zarazaga, C. Torres
Journal: Clinical Microbiology and Infection (2009)
Patients With Ankylosing Spondylitis Have Increased Cardiovascular and Cerebrovascular Mortality
Authors: Nisha Nigil Haroon, J. Michael Paterson, Ping Li, Robert D. Inman, Nigil Haroon
Journal: Annals of Internal Medicine (2015)

Background: Ankylosing spondylitis (AS) is a chronic inflammatory arthritis affecting the spine in young adults. It is associated with excess cardiovascular and cerebrovascular morbidity. Objective: To determine whether patients with AS are at increased risk for cardiovascular and cerebrovascular mortality. Design: Population-based retrospective cohort study using administrative health data. Setting: Ontario, Canada. Patients: 21 473 patients with AS aged 15 years or older and 86 606 comparators without AS, matched for age, sex, and location of residence. Measurements: The primary outcome was a composite of cardiovascular and cerebrovascular death. Hazard ratios (HRs) for vascular death were calculated; adjusted for history of cancer, diabetes, dementia, inflammatory bowel disease, hypertension, chronic kidney disease, and peripheral vascular disease; and, among those aged 66 years or older, relevant drug therapies. Independent risk factors for vascular mortality were identified in patients with AS. Results: The mean age of patients with AS was 46 years, and 53% were male. Patients and comparators were followed for 166 920 and 686 461 patient-years, respectively. Adjusted HRs for vascular death in AS were 1.36 (95% CI, 1.13 to 1.65) overall, 1.46 (CI, 1.13 to 1.87) in men, and 1.24 (CI, 0.92 to 1.67) in women. Significant risk factors for vascular death were age; male sex; lower income; dementia; chronic kidney disease; peripheral vascular disease; and, among patients aged 65 years or older, lack of exposure to nonsteroidal anti-inflammatory drugs and statins. Limitation: Diagnosis codes for AS were not validated in Ontario. Conclusion: Ankylosing spondylitis is associated with increased risk for vascular mortality. A comprehensive strategy to screen and treat modifiable vascular risk factors in AS is needed. Primary Funding Source: The Arthritis Program, University Health Network, Toronto; and The Arthritis Society, Canada.
The relationship between the amount of CD3+ T cells and the clinical pathological parameter in gastric cardia carcinoma
Authors: Xiaoshan Feng, Bo Zhou, Gongping Wang, Shegan Gao
Journal: Clinical Cancer Research (2008)

B34  Introduction: The CD3+ T cells, as an important component of tumor-infiltrating lymphocytes (TIL), has attracted more and more attention recently. In the studies of the CD3+ T cells in liver and colon carcinoma, it has been demonstrated that the amount of the CD3+ T cells in tumor samples has associated with the progress and prognosis of the carcinoma. But there is few report about the CD3+ T cells in gastric cardia carcinoma (GCC).  Aim: To explore the relationship between the amount of CD3+ T cells in GCC samples and the clinical pathological parameter of GCC.  Materials and Methods: Seventy-two cases of samples were analyzed in the study, 42 cases of gastric cardia carcinoma , 18 cases of adjacent mucosa tissue were obtained from the patient who had received the tumor total resection, 12 cases of normal cardiac mucosa tissue were obtained from the patient who had received proximal gastric resection for benign disease.The CD3+ T cells were detected using immunohistochemical Elivision method with the monoclonal antibody in all of these samples.The distribution of the CD3+ T cells was observed and the number of the CD3+ T cells was counted.  Results: (1) The order of the mean number of CD3+ T cells from the highest to lowest was paraneoplastic, GCC and normal mucosa (P 0.05). (3) The mean number of CD3+ T cells was negatively correlated with the depth of carcinoma invasion and the lymphatic metastisis (P