tbuckley/cabot-search huggingface dataset:
Pneumonia risk in COPD patients receiving inhaled corticosteroids alone or in combination: TORCH study results
Authors: C. Crim, P. M. A. Calverley, J. A. Anderson, B. Celli, G. T. Ferguson, C. Jenkins, P. W. Jones, L. R. Willits, J. C. Yates, J. Vestbo
Journal: European Respiratory Journal (2009)

Inhaled corticosteroids (ICS) are important in reducing exacerbation frequency associated with chronic obstructive pulmonary disease (COPD). However, little is known about the risk of associated infections. In a post hoc analysis of the TOwards a Revolution in COPD Health (TORCH) study, we analysed and identified potential risk factors for adverse event reports of pneumonia in this randomised, double-blind trial comparing twice-daily inhaled salmeterol (SAL) 50 μg, fluticasone propionate (FP) 500 μg, and the combination (SFC) with placebo in 6,184 patients with moderate-to-severe COPD over 3 yrs. Despite a higher withdrawal rate in the placebo arm, after adjusting for time on treatment, a greater rate of pneumonia was reported in the FP and SFC treatment arms (84 and 88 per 1,000 treatment-yrs, respectively) compared with SAL and placebo (52 and 52 per 1,000 treatment-yrs, respectively). Risk factors for pneumonia were age ≥55 yrs, forced expiratory volume in 1 s &lt;50% predicted, COPD exacerbations in the year prior to the study, worse Medical Research Council dyspnoea scores and body mass index &lt;25 kg·m −2 . No increase in pneumonia deaths with SFC was observed; this could not be concluded for FP. Despite the benefits of ICS-containing regimens in COPD management, healthcare providers should remain vigilant regarding the possible development of pneumonia as a complication in COPD patients receiving such therapies.
Coffee worker's lung: A new example of extrinsic allergic alveolitis
Authors: D. W. Van Toorn
Journal: Thorax (1970)

A man who worked for more than 20 years in a coffee-roasting factory developed lung lesions. By immunological investigations it was proven that there were circulating antibodies against coffee-bean dust in the patient9s serum. Immunofluorescence of the lung biopsy demonstrated deposits of IgG and complement along the alveolar capillaries. The histological features are described.
International Myeloma Working Group Recommendations for the Treatment of Multiple Myeloma–Related Bone Disease
Authors: Evangelos Terpos, Gareth Morgan, Meletios A. Dimopoulos, Matthew T. Drake, Suzanne Lentzsch, Noopur Raje, Orhan Sezer, Ramón García-Sanz, Kazuyuki Shimizu, Ingemar Turesson, Tony Reiman, Artur Jurczyszyn, Giampaolo Merlini, Andrew Spencer, Xavier Leleu, Michele Cavo, Nikhil Munshi, S. Vincent Rajkumar, Brian G.M. Durie, G. David Roodman
Journal: Journal of Clinical Oncology (2013)

The aim of the International Myeloma Working Group was to develop practice recommendations for the management of multiple myeloma (MM) -related bone disease.An interdisciplinary panel of clinical experts on MM and myeloma bone disease developed recommendations based on published data through August 2012. Expert consensus was used to propose additional recommendations in situations where there were insufficient published data. Levels of evidence and grades of recommendations were assigned and approved by panel members.Bisphosphonates (BPs) should be considered in all patients with MM receiving first-line antimyeloma therapy, regardless of presence of osteolytic bone lesions on conventional radiography. However, it is unknown if BPs offer any advantage in patients with no bone disease assessed by magnetic resonance imaging or positron emission tomography/computed tomography. Intravenous (IV) zoledronic acid (ZOL) or pamidronate (PAM) is recommended for preventing skeletal-related events in patients with MM. ZOL is preferred over oral clodronate in newly diagnosed patients with MM because of its potential antimyeloma effects and survival benefits. BPs should be administered every 3 to 4 weeks IV during initial therapy. ZOL or PAM should be continued in patients with active disease and should be resumed after disease relapse, if discontinued in patients achieving complete or very good partial response. BPs are well tolerated, but preventive strategies must be instituted to avoid renal toxicity or osteonecrosis of the jaw. Kyphoplasty should be considered for symptomatic vertebral compression fractures. Low-dose radiation therapy can be used for palliation of uncontrolled pain, impending pathologic fracture, or spinal cord compression. Orthopedic consultation should be sought for long-bone fractures, spinal cord compression, and vertebral column instability.
An Exon-Capture System for the Entire Class Ophiuroidea
Authors: Andrew F. Hugall, Timothy D. O’Hara, Sumitha Hunjan, Roger Nilsen, Adnan Moussalli
Journal: Molecular Biology and Evolution (2015)

Exon-capture studies have typically been restricted to relatively shallow phylogenetic scales due primarily to hybridization constraints. Here, we present an exon-capture system for an entire class of marine invertebrates, the Ophiuroidea, built upon a phylogenetically diverse transcriptome foundation. The system captures approximately 90% of the 1,552 exon target, across all major lineages of the quarter-billion-year-old extant crown group. Key features of our system are 1) basing the target on an alignment of orthologous genes determined from 52 transcriptomes spanning the phylogenetic diversity and trimmed to remove anything difficult to capture, map, or align; 2) use of multiple artificial representatives based on ancestral state reconstructions rather than exemplars to improve capture and mapping of the target; 3) mapping reads to a multi-reference alignment; and 4) using patterns of site polymorphism to distinguish among paralogy, polyploidy, allelic differences, and sample contamination. The resulting data give a well-resolved tree (currently standing at 417 samples, 275,352 sites, 91% data-complete) that will transform our understanding of ophiuroid evolution and biogeography.
Preoperative Diagnosis of Extrapancreatic Neural Invasion in Pancreatic Cancer
Authors: Michael J. Levy, Mark Topazian, Gary Keeney, Jonathan E. Clain, Ferga Gleeson, Elizabeth Rajan, Kenneth K. Wang, Maurits J. Wiersema, Michael Farnell, Suresh Chari
Journal: Clinical Gastroenterology and Hepatology (2006)
486. Efficient and Selective Gene Transfer Directed to Muscle by Tropism-Modified Adeno- Associated Virus Vector
Authors: Chi-Yi Yu, Bing Wang, Zhong Wang, Zhongren Cao, Juan Li, Xiao Xiao
Journal: Molecular Therapy (2006)

Duchenne muscular dystrophy (DMD) is a lethal genetic muscle disorder that affects one in 3500 males. Transfer of the therapeutic gene into the diseased muscles has great potential for the treatment of DMD patients. Gene delivery vehicles based on recombinant adeno-associated virus (rAAV) have been generated as promising vectors for the correction of genetic diseases. However, rAAV primarily transduces the liver after systemic administration, reducing its efficiency for gene transfer at skeletal muscle.
A Model Citizen? Is Tamoxifen More Effective Than Aromatase Inhibitors if We Pick the Right Patients?
Authors: D. F. Hayes, V. Stearns, J. Rae, D. Flockhart
Journal: JNCI Journal of the National Cancer Institute (2008)

After decades of empiricism, the treatment of cancer is widely felt to be entering the era of “targeted” therapy and leading to personalized strategies for individuals with this dreaded disease. Of course, the approach to targeted therapy in oncology is not a new one. Students of breast cancer history point to Sir George Beatson’s report in 1896 of the clinical improvement he observed in three young women with locally advanced breast cancer following surgical oophorectomy ( 1 ). Subsequent landmark studies by Jensen, Lippman, and McGuire, among others, demonstrated that what Beatson had actually done was remove a specific growth factor, 17 -estradiol, from its cellular target, the estrogen receptor (ER) ( 2 – 4 ). Clinicians now routinely use tissue ER content to individualize antiestrogen therapy for breast cancer patients ( 5 ).
Further evidence in support of a distributed semantic memory system
Authors: Eleanor M. Saffran, H. Branch Coslett
Journal: Behavioral and Brain Sciences (2001)

We offer additional points that support a distributed semantic memory: (1) the activation of representations that are modality-specific; (2) patients with inferotemporal lesions fail to activate visual object representations in semantic tasks, although normal subjects do; (3) direct activation of action systems from pictorial information, but not from words; (4) patients who demonstrate superiority with abstract words fail to access perceptual representations.
Prognosis Research Strategy (PROGRESS) 2: Prognostic Factor Research
Authors: Richard D. Riley, Jill A. Hayden, Ewout W. Steyerberg, Karel G. M. Moons, Keith Abrams, Panayiotis A. Kyzas, Núria Malats, Andrew Briggs, Sara Schroter, Douglas G. Altman, Harry Hemingway
Journal: PLoS Medicine (2013)

Prognostic factor research aims to identify factors associated with subsequent clinical outcome in people with a particular disease or health condition.In this article, the second in the PROGRESS series, the authors discuss the role of prognostic factors in current clinical practice, randomised trials, and developing new interventions, and explain why and how prognostic factor research should be improved.The Guidelines and Guidance section contains advice on conducting and reporting medical research.
The complex morphology of acute kidney injury with microangiopathic hemolytic anemia and hyposplenism
Authors: Thomas Erblich, Peter D. Hill, James Tomlinson, Barbara J Bain
Journal: American Journal of Hematology (2015)

A 62-year-old Caucasian female with a past history of pancreatic cancer presented with acute kidney injury and thrombocytopenia. The pancreatic cancer had been diagnosed four years previously with histology showing a mucinous tumor. She had been treated by extensive resection including splenectomy followed by radiotherapy and gemcitabine chemotherapy. Her disease relapsed one year prior to her current presentation. Despite further intensified treatment with weekly gemcitabine, the disease progressed and she developed pulmonary metastases. On presentation her blood count showed: WBC 9.5 × 109/l, RBC 3.05 × 1012/l, hemoglobin concentration 91 g/l, reticulocyte count 104 × 109/l, and platelet count 89 x 109/l. Creatinine was 285 μmol/l (estimated glomerular filtration rate 15 ml/min/1.73 m2) and lactate dehydrogenase 1320 iu/l. Her blood film (images) showed an unusual constellation of abnormalities. The features of hyposplenism were present, specifically Howell–Jolly bodies, Pappenheimer bodies, target cells and acanthocytes. In addition, there was echinocytosis – consistent with renal disease – and red cell fragmentation plus thrombocytopenia and giant platelets – indicative of microangiopathic hemolytic anemia. Because of the coexisting pathological processes, there were also acanthocytic fragments and echinocytic fragments; occasional fragments contained Howell–Jolly bodies. A diagnosis of atypical hemolytic uremic syndrome was made and plasma exchange and prednisolone were commenced. Prior to plasma exchange, haptoglobin was undetectable and ADAMTS13 was 87%. There are two potential causes of microangiopathic hemolytic anemia in this patient, gemcitabine therapy and progressive malignancy. The acute kidney injury is the result of thrombotic microangiopathy. The blood film was unusually informative, showing evidence of all the pathological processes in operation.
A Meta-analysis of Lung Cancer Gene Expression Identifies <i>PTK7</i> as a Survival Gene in Lung Adenocarcinoma
Authors: Ron Chen, Purvesh Khatri, Pawel K. Mazur, Melanie Polin, Yanyan Zheng, Dedeepya Vaka, Chuong D. Hoang, Joseph Shrager, Yue Xu, Silvestre Vicent, Atul J. Butte, E. Alejandro Sweet-Cordero
Journal: Cancer Research (2014)

Lung cancer remains the most common cause of cancer-related death worldwide and it continues to lack effective treatment. The increasingly large and diverse public databases of lung cancer gene expression constitute a rich source of candidate oncogenic drivers and therapeutic targets. To define novel targets for lung adenocarcinoma, we conducted a large-scale meta-analysis of genes specifically overexpressed in adenocarcinoma. We identified an 11-gene signature that was overexpressed consistently in adenocarcinoma specimens relative to normal lung tissue. Six genes in this signature were specifically overexpressed in adenocarcinoma relative to other subtypes of non-small cell lung cancer (NSCLC). Among these genes was the little studied protein tyrosine kinase PTK7. Immunohistochemical analysis confirmed that PTK7 is highly expressed in primary adenocarcinoma patient samples. RNA interference-mediated attenuation of PTK7 decreased cell viability and increased apoptosis in a subset of adenocarcinoma cell lines. Further, loss of PTK7 activated the MKK7-JNK stress response pathway and impaired tumor growth in xenotransplantation assays. Our work defines PTK7 as a highly and specifically expressed gene in adenocarcinoma and a potential therapeutic target in this subset of NSCLC.
Cellular basis of tolerance in neonatally induced mouse chimeras.
Authors: W K Silvers, W L Elkins, F W Quimby
Journal: The Journal of Experimental Medicine (1975)

In mice, thymectomized as young adults, neonatally induced tolerance persists in the putative absence of cell chimerism. The finding provides evidence that a selective deficiency of specific clones of lymphocytes exists in transplantation tolerance when induced under the conditions of these experiments.
Nuclear factor‐κB activity is down‐regulated in nasal polyps from aspirin‐sensitive asthmatics
Authors: C. Picado, G. Bioque, J. Roca‐Ferrer, L. Pujols, J. Mullol, P. Benitez, O. Bulbena
Journal: Allergy (2003)

Background: We examined whether a decreased activity of nuclear factor(NF)‐κB), a transcriptional regulator of cyclooxygenase‐2 (COX‐2), could account for down‐regulation of COX‐2 in nasal polyps of aspirin‐sensitive asthmatics. Methods: Nasal polyps were obtained from 17 aspirin‐intolerant asthma/rhinitis patients (AIAR; 7 men, mean age 48 ± 12 years) and 23 aspirin‐tolerant asthma/rhinitis patients (ATAR; 12 men, mean age 65 ± 11 years). COX‐2 mRNA expression was measured using semiquantitative reverse transcriptase competitive polymerase chain reaction (RT‐PCR), and the results were expressed as mean ± standard error of 10 6 molecules of mRNA/µg of total RNA. NF‐κB binding was measured with 32 P‐labeled oligonucleotides and electrophoretic mobility shift assay (EMSA), and the results were expressed as a percentage with respect to the mean EMSA obtained in 19 healthy nasal mucosa. Results: The mean levels of COX‐2 mRNA expression (0.25 ± 0.06) and NF‐κB activity (89 ± 13) in nasal polyps from AIAR were significantly lower than in polyps from ATAR (COX‐2 = 1.58 ± 0.50, and NF‐κB = 143 ± 12, P &lt; 0.01 and P &lt; 0.05, respectively). Levels of COX‐2 mRNA and NF‐κB activity in polyps from patients on corticosteroid therapy did not differ statistically from those who were not on this therapy before polypectomy. Conclusion: This study shows that the low expression of COX‐2 mRNA in nasal polyps from aspirin‐sensitive patients is associated with a down‐regulation of NF‐κB activity.
High Procedure Volume Is Strongly Associated With Improved Survival After Lung Cancer Surgery
Authors: Margreet Lüchtenborg, Sharma P. Riaz, Victoria H. Coupland, Eric Lim, Erik Jakobsen, Mark Krasnik, Richard Page, Michael J. Lind, Michael D. Peake, Henrik Møller
Journal: Journal of Clinical Oncology (2013)

Studies have reported an association between hospital volume and survival for non-small-cell lung cancer (NSCLC). We explored this association in England, accounting for case mix and propensity to resect.We analyzed data on 134,293 patients with NSCLC diagnosed in England between 2004 and 2008, of whom 12,862 (9.6%) underwent surgical resection. Hospital volume was defined according to number of patients with resected lung cancer in each hospital in each year of diagnosis. We calculated hazard ratios (HRs) for death in three predefined periods according to hospital volume, sex, age, socioeconomic deprivation, comorbidity, and propensity to resect.There was increased survival in hospitals performing > 150 surgical resections compared with those carrying out < 70 (HR, 0.78; 95% CI, 0.67 to 0.90; Ptrend < .01). The association between hospital volume and survival was present in all three periods of follow-up, but the magnitude of association was greatest in the early postoperative period.High-volume hospitals have higher resection rates and perform surgery among patients who are older, have lower socioeconomic status, and have more comorbidities; despite this, they achieve better survival, most notably in the early postoperative period.
DNA methylation prevents CTCF-mediated silencing of the oncogene <i>BCL6</i> in B cell lymphomas
Authors: Anne Y. Lai, Mehrnaz Fatemi, Archana Dhasarathy, Christine Malone, Steve E. Sobol, Cissy Geigerman, David L. Jaye, Deepak Mav, Ruchir Shah, Leping Li, Paul A. Wade
Journal: The Journal of Experimental Medicine (2010)

Aberrant DNA methylation commonly occurs in cancer cells where it has been implicated in the epigenetic silencing of tumor suppressor genes. Additional roles for DNA methylation, such as transcriptional activation, have been predicted but have yet to be clearly demonstrated. The BCL6 oncogene is implicated in the pathogenesis of germinal center-derived B cell lymphomas. We demonstrate that the intragenic CpG islands within the first intron of the human BCL6 locus were hypermethylated in lymphoma cells that expressed high amounts of BCL6 messenger RNA (mRNA). Inhibition of DNA methyltransferases decreased BCL6 mRNA abundance, suggesting a role for these methylated CpGs in positively regulating BCL6 transcription. The enhancer-blocking transcription factor CTCF bound to this intronic region in a methylation-sensitive manner. Depletion of CTCF by short hairpin RNA in neoplastic plasma cells that do not express BCL6 resulted in up-regulation of BCL6 transcription. These data indicate that BCL6 expression is maintained during lymphomagenesis in part through DNA methylation that prevents CTCF-mediated silencing.
Self-reported determinants of physical activity in COPD patients
Authors: Sigrid Vorrink, Helianthe Kort, Thierry Troosters, Jan-Willem Lammers
Journal: European Respiratory Journal (2012)

Introduction: COPD patients demonstrate reduced levels of daily physical activity compared with healthy controls1.This results in a higher risk of hospital admission and shorter survival2. Performing regular physical activity, reduces the risk of both COPD-related hospital admissions and mortality.  Aim: There is a lack of knowledge in the personal factors that determine whether a person is motivated to be physically active. Which factors cause patients to stay at home and which factors motivate them to be active?  Methods: We developed an online survey using www.surveymonkey.com which was posted on the patient forum of the Dutch Asthma Foundation and on COPD group sites of Hyves, a Dutch friend based site. The questionnaire was online from Oct. 23rd 909 till Jan. 12th 910.  Results: In total 192 COPD patients started the survey and 116 completed (60%). 66% were women and average age was 59±11 years. GOLD grades 1-4 were distributed as 18%, 31%, 32% and 19%, respectively. The top 3 of factors mentioned that stimulate physical activity was: 1. improvement of physical health, 2. the type of physical activity and 3. weather conditions. Demotivating factors were: 1. weather conditions, 2. tiredness and 3. dyspnea.  Conclusion: Most respondents are aware that physical activity influences their physical health. Awareness of the reasons for taking on an action is important in motivating oneself to conduct it. Knowing which factors influence patients to be physically active could be used as predictors for, or to influence physical activity in COPD patients.  references  1. Vorrink et al. Resp. Res. 2011, 12:33  2. Pitta et al. Eur Respir J. 2006 May;27(5):1040-55.
Induction of Tumor-Specific CD4+ and CD8+ T-Cell Immunity in Cervical Cancer Patients by a Human Papillomavirus Type 16 E6 and E7 Long Peptides Vaccine
Authors: Marij J.P. Welters, Gemma G. Kenter, Sytse J. Piersma, Annelies P.G. Vloon, Margriet J.G. Löwik, Dorien M.A. Berends-van der Meer, Jan W. Drijfhout, A. Rob P.M. Valentijn, Amon R. Wafelman, Jaap Oostendorp, Gert Jan Fleuren, Rienk Offringa, Cornelis J.M. Melief, Sjoerd H. van der Burg
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The study aims to evaluate the effect of a human papillomavirus type 16 (HPV16) E6 and E7 synthetic long peptides vaccine on the antigen-specific T-cell response in cervical cancer patients. Experimental Design: Patients with resected HPV16-positive cervical cancer were vaccinated with an overlapping set of long peptides comprising the sequences of the HPV16 E6 and E7 oncoproteins emulsified in Montanide ISA-51. HPV16-specific T-cell immune responses were analyzed by evaluating the magnitude, breadth, type, and polarization by proliferation assays, IFNγ-ELISPOT, and cytokine production and phenotyped by the T-cell markers CD4, CD8, CD25, and Foxp3. Results: Vaccine-induced T-cell responses against HPV16 E6 and E7 were detected in six of six and five of six patients, respectively. These responses were broad, involved both CD4+ and CD8+ T cells, and could be detected up to 12 months after the last vaccination. The vaccine-induced responses were dominated by effector type CD4+CD25+Foxp3− type 1 cytokine IFNγ-producing T cells but also included the expansion of T cells with a CD4+CD25+Foxp3+ phenotype. Conclusions: The HPV16 E6 and E7 synthetic long peptides vaccine is highly immunogenic, in that it increases the number and activity of HPV16-specific CD4+ and CD8+ T cells to a broad array of epitopes in all patients. The expansion of CD4+ and CD8+ tumor-specific T cells, both considered to be important in the antitumor response, indicates the immunotherapeutic potential of this vaccine. Notably, part of the vaccine-induced T cells display a CD4+CD25+Foxp3+ phenotype that is frequently associated with regulatory T-cell function, suggesting that strategies to disarm this subset of T cells should be considered as components of immunotherapeutic modalities against HPV-induced cancers.