tbuckley/cabot-search huggingface dataset:
Feasibility of OSNA in EBUS-TBNA of lung cancer patients
Authors: Kaid Darwiche, Filiz Oezkan, Amir Khan, Dirk Theegarten, Robert Walter, Lutz Freitag
Journal: European Respiratory Journal (2014)

Introduction 

One Step Nucleic Acid Amplification (OSNA) is a new method in quick detection of sentinel lymph node (SLN) worldwide in breast cancer. OSNA obviates the need for axillary dissection and helps expedite clinical decision making to adjuvant therapy.In lung cancer, regional lymph nodes are assessed before tumor resection. EBUS-TBNA is a well established method for mediastinal lymph node staging providing only small samples instead of surgical biopsies. Our study evaluates OSNA in EBUS-TBNA specimen of lung cancer patients.

Methods and Materials 

We used OSNA with reverse transcription loop-mediated isothermal amplification (RT-LAMP). Using the Lynoamp amplification kit in the RD-100i (Sysmex, Japan), CK19 mRNA concentration was detected. Samples with a CK19 mRNA copy number above 250 copies/µl were regarded as positive, less than 250 copies/ul were defined as negative. We used histopathologic evaluation for standard comparison. 19 EBUS-TBNA lymph node samples were obtained during routine staging. Approximately 3-7 mg of each sample was used for OSNA analysis.

Results 

In 19 patients suspected to have lymph node metastases we found 7 adenocarcinoma, 5 squamous cell carcinoma, 6 small cell lung cancer and 1 negative sample. 15 of 18 patients were detected by OSNA. One negative lymph node was also detected OSNA negative. Overall sensitivity, specificity, positive and negative predictive value and accuracy was 83,3 %, 100%, 100%, 25%, 84,2% respectively. Total procedural time was about 45 minutes for 4 samples.

Conclusion 

OSNA can provide quick and accurate information regarding dignity of EBUS-TBNA specimen. Our preliminary study shows that OSNA may play an important role in diagnosing and staging of lung cancer.
Structural robustness of the gut mucosal microbiota is associated with Crohn's disease remission after surgery
Authors: S Mondot, P Lepage, P Seksik, M Allez, X Tréton, Y Bouhnik, J F Colombel, M Leclerc, P Pochart, J Doré, P Marteau
Journal: Gut (2015)

Preventing postoperative recurrence after ileocolonic resection (ICR) for Crohn's disease (CD) is challenging. Defining the disturbances of the microbial composition and community structure after ICR and their link with early disease recurrence is crucial.Microbiota composition (fingerprinting and 16S rDNA sequencing) and community structure (correlation networks of bacterial species) were assessed from ileal mucosa sampled in 20 patients undergoing ICR and 6 months later during endoscopy from above (neoterminal ileum) and below (subanastomotic colon) the surgical anastomosis.ICR had a dramatic effect on gut microbial ecosystem. At surgery, CD mucosa harboured a dysbiotic microbiota with high proportions of α/β Proteobacteria and Bacilli. Six months later, half of the patients had recurrent lesions at ileocolonoscopy and presented higher numbers of Lachnospiraceae. Recurrence of endoscopic lesions was associated with enrichment in Enterococcus durans while patients in remission had increased proportions of Dorea longicatena and Bacteroides plebeius. Structural differences were striking between recurrence and remission microbiota; while the microbiota of patients with CD recurrence exhibited a loose community structure, the microbiota of patients in remission displayed communities that were robustly correlated to each other. Microbiota colonising the neoterminal ileum and subanastomotic colon 6 months after ICR only differed in patients with recurrence.ICR modifies the gut microbiome. Remission after 6 months was associated with homogenous bacterial distribution around the anastomosis. Community structure and bacterial networks highlight target species, including Faecalibacterium prausnitzii and Ruminococcus gnavus, which may allow precise modulations of the overall microbial ecosystem towards remission pattern.
Antimicrobial resistance: a veterinary perspective
Authors: Q A McKellar
Journal: BMJ (1998)

<b>Background:</b> Liver transplantation is a very successful therapy for those with end stage disease. Although there are numerous data on patient and graft survival after liver transplantation, life expectancy and possible loss of life (compared with a normal matched population) in those who survive remains unknown. <b>Aims:</b> To assess the life expectancy and life years lost of adult liver allograft recipients, compared with an age and sex matched UK population to provide patients with more information and to improve the use of a scarce resource. <b>Methods:</b> Using the National Transplant Database held by UK Transplant, on over 3600 adult liver allograft recipients transplanted between 1985 and 2003, we analysed survival of all adults who survived more than six months after transplantation and compared survival after transplantation with national age and sex matched controls to assess life years lost. <b>Results:</b> Estimated median survival time of the analysis cohort of 2702 adult liver allograft recipients was 22.2 years (95% confidence interval 19.3–25.6), with an estimated loss of seven life years compared with an age and sex matched population. <b>Conclusions:</b> Overall, female recipients have a longer life expectancy and lose fewer life years than male recipients. While younger recipients have a longer life expectancy, they also lose more life years. Those transplanted for cancer, hepatitis C virus infection, and alcoholic liver disease had the greatest loss of life years.
Nocturnal eczema: Review of sleep and circadian rhythms in children with atopic dermatitis and future research directions
Authors: Anna B. Fishbein, Olivia Vitaterna, Isabel M. Haugh, Aakash A. Bavishi, Phyllis C. Zee, Fred W. Turek, Stephen H. Sheldon, Jonathan I. Silverberg, Amy S. Paller
Journal: Journal of Allergy and Clinical Immunology (2015)
UK’s approval of mitochondrial donation shows how decisions on gene editing can be made
Authors: Nigel Hawkes
Journal: BMJ (2015)

The approval in the United Kingdom of mitochondrial donation provides a blueprint for future decisions on modifying the genome, the government’s chief scientific adviser told a conference in London on Wednesday 9 December.

Mark Walport said that the UK should be proud of the process through which mitochondrial donation was approved, culminating in votes in parliament earlier this year and regulations that came into force on 29 October.1 These made it possible for women with abnormalities in the mitochondrial DNA of their eggs to avoid giving birth to unhealthy children by replacing that DNA with donated material.

Several steps remain before the technique is actually used, the chair of the Human Fertilisation and Embryology Authority, Sally Chaplin, told the Progress Educational Trust’s annual conference. “Once final safety and efficacy tests are completed, we will be able to offer licences to …
Maternal Occupational Exposure to Noise during Pregnancy and Hearing Dysfunction in Children: A Nationwide Prospective Cohort Study in Sweden
Authors: Jenny Selander, Maria Albin, Ulf Rosenhall, Lars Rylander, Marie Lewné, Per Gustavsson
Journal: Environmental Health Perspectives (2015)

Many women of childbearing age are occupationally active, which leads to a large number of pregnancies potentially exposed to occupational exposures. Occupational noise has been identified as a risk factor for hearing impairment in adults. However, very few studies have assessed the effect of occupational noise on the fetus.The aim of this study was to investigate whether occupational exposure to noise during pregnancy is associated with hearing dysfunction in children.This population based cohort study included 1,422,333 single births in Sweden 1986-2008. Data on mothers' occupation, smoking habits, age, ethnicity, body mass index, leave of absence, and socioeconomic factors were obtained from interviews performed by prenatal care unit staff at approximately 10 weeks of gestation and from national registers. Occupational noise exposure was classified by a job-exposure-matrix as < 75, 75-84, or ≥ 85 dBLAeq,8h. Diagnosed cases of hearing dysfunction (ICD-10 codes H90.3-7, 91.0, 91.2-3, 91.8, 93.1-2) were identified from a register of specialized medical care. Cox proportional hazards models were used to estimate associations.In the full sample, containing a mixture of part-time and full-time workers during pregnancy, the adjusted HR for hearing dysfunction associated with maternal occupational noise exposure ≥ 85 vs. < 75 dBLAeq,8h was 1.27 (95% CI: 0.99, 1.64; 60 exposed cases). When restricted to children whose mothers worked full-time and had < 20 days leave of absence during pregnancy, the corresponding HR was 1.82 (95% CI: 1.08, 3.08; 14 exposed cases).This study showed an association between occupational noise exposure during pregnancy and hearing dysfunction in children. In view of mechanistic evidence and earlier indicative epidemiological and experimental findings, the results support that pregnant women should not be exposed to high levels of noise at work.Selander J, Albin M, Rosenhall U, Rylander L, Lewné M, Gustavsson P. 2016. Maternal occupational exposure to noise during pregnancy and hearing dysfunction in children: a nationwide prospective cohort study in Sweden. Environ Health Perspect 124:855-860; http://dx.doi.org/10.1289/ehp.1509874.
Peptide–Drug Conjugate GnRH–Sunitinib Targets Angiogenesis Selectively at the Site of Action to Inhibit Tumor Growth
Authors: Orestis Argyros, Theodoros Karampelas, Xenophon Asvos, Aimilia Varela, Nisar Sayyad, Athanasios Papakyriakou, Constantinos H. Davos, Andreas G. Tzakos, Demosthenes Fokas, Constantin Tamvakopoulos
Journal: Cancer Research (2015)

The potential to heighten the efficacy of antiangiogenic agents was explored in this study based on active targeting of tumor cells overexpressing the gonadotropin-releasing hormone receptor (GnRH-R). The rational design pursued focused on five analogues of a clinically established antiangiogenic compound (sunitinib), from which a lead candidate (SAN1) was conjugated to the targeting peptide [d-Lys(6)]-GnRH, generating SAN1GSC. Conjugation of SAN1 did not disrupt any of its antiangiogenic or cytotoxic properties in GnRH-R-expressing prostate and breast tumor cells. Daily SAN1GSC treatments in mouse xenograft models of castration-resistant prostate cancer resulted in significant tumor growth delay compared with equimolar SAN1 or sunitinib alone. This efficacy correlated with inhibited phosphorylation of AKT and S6, together with reduced Ki-67 and CD31 expression. The superior efficacy of the peptide-drug conjugate was also attributed to the finding that higher amounts of SAN1 were delivered to the tumor site (∼4-fold) following dosing of SAN1GSC compared with equimolar amounts of nonconjugated SAN1. Importantly, treatment with SAN1GSC was associated with minimal hematotoxicity and cardiotoxicity based on measurements of the left ventricular systolic function in treated mice. Our results offer preclinical proof-of-concept for SAN1GSC as a novel molecule that selectively reaches the tumor site and downregulates angiogenesis with negligible cardiotoxicity, thus encouraging its further clinical development and evaluation.
Oral contraceptives and thromboembolic disease. Prospective and retrospective studies.
Authors: V. A. Drill
Journal: JAMA (1972)

Tabulated data are presented of the incidence of thromboembolism in prospective studies.  For nonpregnant women of childbearing age a mean of .9 cases per 1000 women per year based on hospital admissions and a mean of 2.2 cases per 1000 women per year based on visits to physicians are diagnosed as thromboembolism.  A mean of 9.8 cases per 1000 postpartum women per year was computed from 6 studies.  A mean incidence of .46 cases per 1000 pregnant women per 9 months of pregnancy was calculated from 16 publications.  15 prospective oral contraceptive studies of 1000 woman-years or more yielded a mean incidence of .92 cases per 1000 women per year.  In 45 small scale prospective trials of oral contraceptives the mean incidence was 1.22 cases per 1000 women per year.  The author maintains that the retrospective studies only introduce the hypothesis that oral contraceptives increase the risk of thromboembolism which the prospective studies refute.
WHO European region reports no indigenous cases of malaria for first time
Authors: Anne Gulland
Journal: BMJ (2015)

The World Health Organization’s European region has reported no indigenous cases of malaria for the first time, new data have shown.

The World Malaria Report 2015 1 showed that the region—which to the east includes Azerbaijan, Armenia, Tajikistan, and Uzbekistan—has reported no home grown cases of malaria this year. This milestone is in line with the goal to eliminate malaria from the region by the end of 2015, after a peak of 90 712 cases in 1995.

The number of countries reporting fewer than 1000 cases of …
Choline Kinase Alpha as an Androgen Receptor Chaperone and Prostate Cancer Therapeutic Target
Authors: Mohammad Asim, Charles E Massie, Folake Orafidiya, Nelma Pértega-Gomes, Anne Y Warren, Mohsen Esmaeili, Luke A Selth, Heather I Zecchini, Katarina Luko, Arham Qureshi, Ajoeb Baridi, Suraj Menon, Basetti Madhu, Carlos Escriu, Scott Lyons, Sarah L Vowler, Vincent R Zecchini, Greg Shaw, Wiebke Hessenkemper, Roslin Russell, Hisham Mohammed, Niki Stefanos, Andy G Lynch, Elena Grigorenko, Clive D'Santos, Chris Taylor, Alastair Lamb, Rouchelle Sriranjan, Jiali Yang, Rory Stark, Scott M Dehm, Paul S Rennie, Jason S Carroll, John R Griffiths, Simon Tavaré, Ian G Mills, Iain J McEwan, Aria Baniahmad, Wayne D Tilley, David E Neal
Journal: JNCI Journal of the National Cancer Institute (2015)

The androgen receptor (AR) is a major drug target in prostate cancer (PCa). We profiled the AR-regulated kinome to identify clinically relevant and druggable effectors of AR signaling. Using genome-wide approaches, we interrogated all AR regulated kinases. Among these, choline kinase alpha (CHKA) expression was evaluated in benign (n = 195), prostatic intraepithelial neoplasia (PIN) (n = 153) and prostate cancer (PCa) lesions (n = 359). We interrogated how CHKA regulates AR signaling using biochemical assays and investigated androgen regulation of CHKA expression in men with PCa, both untreated (n = 20) and treated with an androgen biosynthesis inhibitor degarelix (n = 27). We studied the effect of CHKA inhibition on the PCa transcriptome using RNA sequencing and tested the effect of CHKA inhibition on cell growth, clonogenic survival and invasion. Tumor xenografts (n = 6 per group) were generated in mice using genetically engineered prostate cancer cells with inducible CHKA knockdown. Data were analyzed with χ 2 tests, Cox regression analysis, and Kaplan-Meier methods. All statistical tests were two-sided. CHKA expression was shown to be androgen regulated in cell lines, xenografts, and human tissue (log fold change from 6.75 to 6.59, P = .002) and was positively associated with tumor stage. CHKA binds directly to the ligand-binding domain (LBD) of AR, enhancing its stability. As such, CHKA is the first kinase identified as an AR chaperone. Inhibition of CHKA repressed the AR transcriptional program including pathways enriched for regulation of protein folding, decreased AR protein levels, and inhibited the growth of PCa cell lines, human PCa explants, and tumor xenografts. CHKA can act as an AR chaperone, providing, to our knowledge, the first evidence for kinases as molecular chaperones, making CHKA both a marker of tumor progression and a potential therapeutic target for PCa.
Short- Versus Long-Term Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation
Authors: Tullio Palmerini, Diego Sangiorgi, Marco Valgimigli, Giuseppe Biondi-Zoccai, Fausto Feres, Alexandre Abizaid, Ricardo A. Costa, Myeong-Ki Hong, Byeong-Keuk Kim, Yangsoo Jang, Hyo-Soo Kim, Kyung Woo Park, Andrea Mariani, Diego Della Riva, Philippe Genereux, Martin B. Leon, Deepak L. Bhatt, Umberto Bendetto, Claudio Rapezzi, Gregg W. Stone
Journal: Journal of the American College of Cardiology (2015)
Androgen Deprivation Therapy and Future Alzheimer’s Disease Risk
Authors: Kevin T. Nead, Greg Gaskin, Cariad Chester, Samuel Swisher-McClure, Joel T. Dudley, Nicholas J. Leeper, Nigam H. Shah
Journal: Journal of Clinical Oncology (2015)

To test the association of androgen deprivation therapy (ADT) in the treatment of prostate cancer with subsequent Alzheimer's disease risk.We used a previously validated and implemented text-processing pipeline to analyze electronic medical record data in a retrospective cohort of patients at Stanford University and Mt. Sinai hospitals. Specifically, we extracted International Classification of Diseases-9th revision diagnosis and Current Procedural Terminology codes, medication lists, and positive-present mentions of drug and disease concepts from all clinical notes. We then tested the effect of ADT on risk of Alzheimer's disease using 1:5 propensity score-matched and traditional multivariable-adjusted Cox proportional hazards models. The duration of ADT use was also tested for association with Alzheimer's disease risk.There were 16,888 individuals with prostate cancer meeting all inclusion and exclusion criteria, with 2,397 (14.2%) receiving ADT during a median follow-up period of 2.7 years (interquartile range, 1.0-5.4 years). Propensity score-matched analysis (hazard ratio, 1.88; 95% CI, 1.10 to 3.20; P = .021) and traditional multivariable-adjusted Cox regression analysis (hazard ratio, 1.66; 95% CI, 1.05 to 2.64; P = .031) both supported a statistically significant association between ADT use and Alzheimer's disease risk. We also observed a statistically significant increased risk of Alzheimer's disease with increasing duration of ADT (P = .016).Our results support an association between the use of ADT in the treatment of prostate cancer and an increased risk of Alzheimer's disease in a general population cohort. This study demonstrates the utility of novel methods to analyze electronic medical record data to generate practice-based evidence.
Idiopathic Ventricular Arrhythmias Originating From the Pulmonary Sinus Cusp
Authors: Zili Liao, Xianzhang Zhan, Shulin Wu, Yumei Xue, Xianhong Fang, Hongtao Liao, Hai Deng, Yuanhong Liang, Wei Wei, Yang Liu, Feifan Ouyang
Journal: Journal of the American College of Cardiology (2015)
Change in adiponectin explains most of the change in HDL particles induced by lifestyle intervention but not metformin treatment in the Diabetes Prevention Program
Authors: Ronald B. Goldberg, Marinella Temprosa, Lisa Mele, Trevor Orchard, Kieren Mather, George Bray, Edward Horton, Abbas Kitabchi, Jonathan Krakoff, Santica Marcovina, Leigh Perreault, Neil White
Journal: Metabolism (2015)
Safety of live attenuated influenza vaccine in young people with egg allergy: multicentre prospective cohort study
Authors: Paul J Turner, Jo Southern, Nick J Andrews, Elizabeth Miller, Michel Erlewyn-Lajeunesse
Journal: BMJ (2015)

How safe is live attenuated influenza vaccine (LAIV), which contains egg protein, in young people with egg allergy?In this open label, phase IV intervention study, 779 young people (2-18 years) with egg allergy were recruited from 30 UK allergy centres and immunised with LAIV. The cohort included 270 (34.7%) young people with previous anaphylaxis to egg, of whom 157 (20.1%) had experienced respiratory and/or cardiovascular symptoms. 445 (57.1%) had doctor diagnosed asthma or recurrent wheeze. Participants were observed for at least 30 minutes after vaccination and followed-up by telephone 72 hours later. Participants with a history of recurrent wheeze or asthma underwent further follow-up four weeks later. The main outcome measure was incidence of an adverse event within two hours of vaccination in young people with egg allergy.No systemic allergic reactions occurred (upper 95% confidence interval for population 0.47% and in participants with anaphylaxis to egg 1.36%). Nine participants (1.2%, 95% CI 0.5% to 2.2%) experienced mild symptoms, potentially consistent with a local, IgE mediated allergic reaction. Delayed events potentially related to the vaccine were reported in 221 participants. 62 participants (8.1%, 95% CI for population 6.3% to 10.3%) experienced lower respiratory tract symptoms within 72 hours, including 29 with parent reported wheeze. No participants were admitted to hospital. No increase in lower respiratory tract symptoms occurred in the four weeks after vaccination (assessed with asthma control test). The study cohort may represent young people with more severe allergy requiring specialist input, since they were recruited from secondary and tertiary allergy centres.LAIV is associated with a low risk of systemic allergic reactions in young people with egg allergy. The vaccine seems to be well tolerated in those with well controlled asthma or recurrent wheeze.This report is independent research commissioned and funded by a Department of Health policy research programme grant to the National Vaccine Evaluation Consortium. Additional funding was provided by the NIHR Clinical Research Networks, Health Protection Scotland (Edinburgh site), and Health & Social Care Services in Northern Ireland (Belfast site). PJT and MEL had support from the Department of Health for the submitted work; PJT has received research grants from the Medical Research Council and NIHR. No additional data available.Study registration ClinicalTrials.gov (NCT02111512) and the EU Clinical Trials Register EudraCT (2014-001537-92).
Qualitative Research: Consensus methods for medical and health services research
Authors: J. Jones, D. Hunter
Journal: BMJ (1995)

Health providers face the problem of trying to make decisions in situations where there is insufficient information and also where there is an overload of (often contradictory) information. Statistical methods such as meta-analysis have been developed to summarise and to resolve inconsistencies in study findings--where information is available in an appropriate form. Consensus methods provide another means of synthesising information, but are liable to use a wider range of information than is common in statistical methods, and where published information is inadequate or non-existent these methods provide a means of harnessing the insights of appropriate experts to enable decisions to be made. Two consensus methods commonly adopted in medical, nursing, and health services research--the Delphi process and the nominal group technique (also known as the expert panel)--are described, together with the most appropriate situations for using them; an outline of the process involved in undertaking a study using each method is supplemented by illustrations of the authors' work. Key methodological issues in using the methods are discussed, along with the distinct contribution of consensus methods as aids to decision making, both in clinical practice and in health service development.
Contribution of APOBEC3G/F activity to the development of low-abundance drug-resistant human immunodeficiency virus type 1 variants
Authors: M. Noguera-Julian, A. Cozzi-Lepri, F. Di Giallonardo, R. Schuurman, M. Däumer, S. Aitken, F. Ceccherini-Silberstein, A. D'Arminio Monforte, A.M. Geretti, C.L. Booth, R. Kaiser, C. Michalik, K. Jansen, B. Masquelier, P. Bellecave, R.D. Kouyos, E. Castro, H. Furrer, A. Schultze, H.F. Günthard, F. Brun-Vezinet, K.J. Metzner, R. Paredes, Roger Paredes, Karin J. Metzner, Alessandro Cozzi-Lepri, Rob Schuurman, Francoise Brun-Vezinet, Huldrych Günthard, Francesca Ceccherini-Silberstein, Rolf Kaiser, Anna Maria Geretti, Norbert Brockmeyer, Bernard Masquelier
Journal: Clinical Microbiology and Infection (2015)