tbuckley/cabot-search huggingface dataset:
The Airway Transcriptome as a Biomarker for Early Lung Cancer Detection
Authors: Ehab Billatos, Jessica L. Vick, Marc E. Lenburg, Avrum E. Spira
Journal: Clinical Cancer Research (2018)

Lung cancer remains the leading cause of cancer-related death due to its advanced stage at diagnosis. Early detection of lung cancer can be improved by better defining who should be screened radiographically and determining which imaging-detected pulmonary nodules are malignant. Gene expression biomarkers measured in normal-appearing airway epithelium provide an opportunity to use lung cancer-associated molecular changes in this tissue for early detection of lung cancer. Molecular changes in the airway may result from an etiologic field of injury and/or field cancerization. The etiologic field of injury reflects the aberrant physiologic response to carcinogen exposure that creates a susceptible microenvironment for cancer initiation. In contrast, field cancerization reflects effects of "first-hit" mutations in a clone of cells from which the tumor ultimately arises or the effects of the tumor on the surrounding tissue. These fields might have value both for assessing lung cancer risk and diagnosis. Cancer-associated gene expression changes in the bronchial airway have recently been used to develop and validate a 23-gene classifier that improves the diagnostic yield of bronchoscopy for lung cancer among intermediate-risk patients. Recent studies have demonstrated that these lung cancer-related gene expression changes extend to nasal epithelial cells that can be sampled noninvasively. While the bronchial gene expression biomarker is being adopted clinically, further work is necessary to explore the potential clinical utility of gene expression profiling in the nasal epithelium for lung cancer diagnosis, lung cancer risk assessment, and precision medicine for lung cancer treatment and chemoprevention.
Abstract P217: Dietary Habits Associated With 6- and 24-month Weight Loss Maintenance in Primary Care Patients
Authors: Bethany Barone Gibbs, Dana Tudorascu, Cindy Bryce, Diane Comer, Gary Fischer, Rachel Hess, Kimberly Huber, Kathleen McTigue, Laurey Simkin-Silverman, Margaret B Conroy
Journal: Circulation (2018)

Introduction: Though weight loss can improve health, weight regain is common. Primary care physicians are uniquely positioned to provide counseling for weight loss maintenance given their longitudinal care of patients, yet evidence of simple lifestyle recommendations for maintaining weight loss in primary care patients is lacking. Our objective was to characterize longitudinal associations between diet habits and weight change among primary care patients with recent, intentional weight loss of at least 5%. Methods: This was a secondary analysis of data from a weight loss maintenance clinical trial in a primary care setting that compared two interventions delivered through the electronic health record: continued coaching vs. tracking only. Dietary habits [fried foods, desserts, fruits and vegetables (F&amp;V), and sugar-sweetened beverages (SSB)] were measured by the Connor Diet Habits Survey. Linear regression models were used to evaluate associations (overall and by randomized group) between changes in dietary habits and weight separately at 6- and 24-month follow-up, adjusted for baseline diet habit, age, gender and clinic location. Results: Participants (n=192) were 74% female, 87% white and had baseline mean (SD) age of 53 (12) years, body mass index of 30.4 (5.9) kg/m 2 , and recent weight loss of 11 (8) percent. Overall, participants had mean (SD) weight loss of 0.18 (5.04) kg at 6 months (n=169) and weight gain of 3.26 (7.60) kg at 24 months (n=140). At 6 months, a 1 serving per week increase in dessert intake was associated with 0.53 kg (p=0.030) greater weight gain. Fried foods, F&amp;V, and SSB were not associated with 6-month weight changes. However, by 24 months, an increase of 1 serving per week was associated with greater weight gain of 0.54 kg (p=0.043) for fried foods, 0.80 kg (p=0.031) for desserts, and 2.01 kg (p=0.002) for SSB. A decrease of 1 F&amp;V serving per day was associated with a 0.82 kg (p=0.008) greater weight gain at 24 months. When stratified by randomized group, associations were stronger in the continued coaching vs. tracking only arm. Conclusions: Increased consumption of desserts was associated with weight regain at 6 and 24 months, while increased fried foods and SSB, and decreased F&amp;V were associated with weight regain at 24 months. These data suggest that simple strategies such as improving or at least maintaining dietary intake of fried foods, desserts, F&amp;V, and SSB could help facilitate long-term weight loss maintenance in primary care patients.
Abstract ES2-2: Clinical management of women with increased breast cancer risk based on histologic lesions
Authors: AC Degnim
Journal: Cancer Research (2018)

Abstract The objective of this lecture is to review clinical management of women with the following histologic lesions associated with increased breast cancer risk: flat epithelial atypia (FEA), atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), and lobular carcinoma in situ (LCIS). Women found to have one or more of these histologic findings in a benign breast biopsy have an increased risk of developing a future breast cancer. Published data will be reviewed that provides estimates of annual and longterm risk associated with these lesions. In addition, management of these lesions after core biopsy will be discussed, specifically the circumstances when surgical excision is recommended. Medical and surgical options for breast cancer risk reduction will be reviewed, as well as their appropriate clinical indications. Citation Format: Degnim AC. Clinical management of women with increased breast cancer risk based on histologic lesions [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr ES2-2.
I want to know the career prospects of a doctor who is HBsAg positive, and what the implications are for a future job and specialisation in paediatrics. Will it be possible for an overseas trained doctor with hepatitis B to pursue a career as a paediatrician?
Authors: Shakeel Ahmed Qureshi
Journal: BMJ (2006)

Have a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site. <b>www.bmjcareers.com/advicezone</b>
Abstract P021: Oral Anticoagulant Use and Risk of Incident Dementia in Persons With Atrial Fibrillation
Authors: Nemin Chen, Richard F MacLehose, Lin Y Chen, Faye L Norby, Lindsay G Bengtson, Wesley T O’Neal, Alanna M Chamberlain, J’Neka S Claxton, Pamela L Lutsey, Alvaro Alonso
Journal: Circulation (2018)

Background: Current guidelines recommend oral anticoagulation for the prevention of stroke in most patients with atrial fibrillation (AF). Direct oral anticoagulants (DOACs) are associated with lower risk of ischemic stroke and intracranial bleeding than warfarin and, therefore, may reduce risk of dementia among patients with AF. Hypothesis: AF patients initiating DOACs for stroke prevention will have lower risk of dementia than patients initiating warfarin. Methods: We used data from two US healthcare claim databases, MarketScan (2007-2015) and Optum Clinformatics (2009-2015). Using validated algorithms, we identified patients with AF who initiated oral anticoagulation. Dementia was defined as having an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code of 290.xx, 294.xx, or 331.0. Comorbidities and use of other medications were defined based on inpatient, outpatient, and pharmacy claims. We performed a series of head-to-head comparisons of different oral anticoagulants (warfarin, dabigatran, rivaroxaban, and apixaban) in propensity score-matched cohorts. In each database, multivariable-adjusted Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident dementia for each comparison of propensity score-matched cohorts, adjusting for age, sex, comorbidities, use of other medications, and markers of socioeconomic status (in the Optum database only). We meta-analyzed database-specific results using a random-effects model. Results: The analysis included 307,099 AF patients from the MarketScan database and 161,346 from the Optum database, of which 6,572 and 4,391 respectively had a diagnosis of incident dementia. Mean follow up ranged between 0.7 to 2.3 years and incident of diagnosed dementia between 7 to 14 cases per 1000 person-years across different oral anticoagulant initiator groups. Patients initiating DOACs had a lower risk of incident dementia than those initiating warfarin (dabigatran: HR 0.85, 95%CI 0.71, 1.01; rivaroxaban: HR 0.85, 95%CI 0.76, 0.94; apixaban: HR 0.80, 95%CI 0.65, 0.97). There were no differences in risk of incident dementia comparing DOAC user groups (dabigatran vs. rivaroxaban: HR 1.02, 95%CI 0.79, 1.32; dabigatran vs. apixaban: HR 0.92, 95%CI 0.63, 1.36; apixaban vs. rivaroxaban: HR 1.01, 95%CI 0.86, 1.19). Conclusions: Patients with AF initiating DOACs experienced lower rates of incident dementia than warfarin users. No obvious benefit was observed for any particular DOAC in relation to dementia rates.
Molecular profiling of liquid biopsies from patients (pts) with bone metastatic castration-resistant prostate cancer (BM-CRPC) treated with radium-223 (RA-223) to reveal differential enrichment for markers that correlate with overall survival (OS).
Authors: Paul Gettys Corn, Sumit Kumar Subudhi, John C. Araujo, Ioulia Vardaki, Ana Aparicio, Shi-Ming Tu, Lance C. Pagliaro, Amado J. Zurita, Christopher Logothetis, Theocharis Panaretakis
Journal: Journal of Clinical Oncology (2018)

259 Introduction: RA-223 prolongs OS in BM-CRPC pts but predictive markers are lacking. We hypothesized that molecular profiling of plasma-derived extracellular vesicles (EVs) from BM-CRPC pts treated with RA-223 would predict efficacy and inform development of combinations. Methods: Paired baseline (BL) and end of treatment (EoT) blood samples were collected from 25 pts treated with RA-223. Pts were stratified by median OS into 3 groups: 1) 6.3 months (range 3.3-8.5, n=5 pts, UnFav OS), 2) 18.2 months (range 12.6-19.4, n=7 pts, Middle OS) and 3) 27.6 months (range 23.1-33.8, n=13 pts, Fav OS). EVs were isolated from plasma and analyzed for specific proteins and RNA transcripts. Marker profiles by domain and analytic method were determined in pts from the stratified OS groups. Results: At EoT, there is enrichment of RNA transcripts and proteins involved in regulating immune responses, DNA Damage Response (DDR) and bone metabolism (Table). By benchmarking molecular signatures in pts with UnFav Os and Fav OS, we could analyze the molecular profiles of pts in the Middle OS group and stratify them to UnFav OS or Fav OS groups. Conclusion: Plasma-based molecular markers are predictive for RA-223 efficacy. An association between OS and immune and DDR profiles in men with BM-CRPC may indicate mechanism of action and identify subsets most likely to benefit. These preliminary results provide rationale for combination therapy with RA-223 and immune-checkpoint blockade or PARP inhibition. Clinical trial information: NCT02135484. [Table: see text]
Incremental Diagnostic Value of Stress Computed Tomography Myocardial Perfusion With Whole-Heart Coverage CT Scanner in Intermediate- to High-Risk Symptomatic Patients Suspected of Coronary Artery Disease
Authors: Gianluca Pontone, Daniele Andreini, Andrea I. Guaricci, Andrea Baggiano, Fabio Fazzari, Marco Guglielmo, Giuseppe Muscogiuri, Claudio Maria Berzovini, Annalisa Pasquini, Saima Mushtaq, Edoardo Conte, Giuseppe Calligaris, Stefano De Martini, Cristina Ferrari, Stefano Galli, Luca Grancini, Paolo Ravagnani, Giovanni Teruzzi, Daniela Trabattoni, Franco Fabbiocchi, Alessandro Lualdi, Piero Montorsi, Mark G. Rabbat, Antonio L. Bartorelli, Mauro Pepi
Journal: JACC. Cardiovascular imaging (2018)
P110 TOFACITINIB is associated with an impaired function of NK cells and a defective immunosurveillance against B-cell lymphomas
Authors: G Nocturne, J Pascaud, B Ly, F Tahmasebi, S Boudaoud, R Seror, L Stimmer, X Mariette
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> Patients with rheumatoid arthritis (RA) are exposed to an increased risk of lymphoma and the impact of treatments is difficult to assess. Tofacitinib, an oral Janus Kinase (Jak) 3 and 1 inhibitor that has shown positive results in RA patients, may impair NK-cell function due to its inhibitory action on IL2 and IL15 signalling. <h3>Objectives</h3> Given the fact that NK cells have been recently shown to participate to anti–lymphoma immunosurveillance, we aimed to assess if tofacitinib might impact NK-cell function and anti-lymphoma activity <i>in vitro</i> and <i>in vivo</i> in BAFF transgenic mice (a model of B cell autoimmunity associated with an increased risk of lymphoma). <h3>Methods</h3> We have studied the consequences of <i>in vitro</i> exposure of NK to tofacitinib (10, 50 and 100 nM) or to DMSO (vehicle) during 6 days in presence of IL-2 (200 UI/ml): phenotype has been studied and then cytotoxicity against 2 non-Hodgkin B-cell lymphoma cell lines [Farage (EBV+) and SU-DHL4 (EBV-)] was assessed. In addition, BAFF transgenic mice were treated for 6 months with tofacitinib (2.25 mg/kg/d n=11; 4.5 mg/kg/d n=10) or vehicle (PEG: DMSO, n=6). Incidence of lymphoma was assessed by histologic examination using a composite score. <h3>Results</h3> Firstly, we did not observe difference concerning the survival of NK cells in presence of tofacitinib or vehicle after 6 day culture. Secondly, we observed that culture in presence of tofacitinib was associated with a decreased level of activation with a dose effect. In addition, we observed a decreased expression of activating receptors such as NKp30, NKp44 and NKG2D. Last, we found that tofacitinib blocked NK cell maturation as observed with the significant decreased expression of CD57 on NK cells exposed to tofacitinib at 50 and 100 nM. These phenotypic abnormalities were associated with an impaired function of NK as assessed by co-culture: degranulation and cytotoxicity were significantly decreased after exposure to tofacitinib. In BAFF transgenic mice, the crude mortality and incidence of lymphoma did not differ between the 3 groups of treatment. <h3>Conclusions</h3> This study demonstrates that tofacitinib treatment negatively impact the state of activation, maturation and functions of NK cells. These defects were not associated with a higher incidence of lymphoma in BAFF Tg mice after 6 months of exposure. However, this negative impact of tofacitinib on NK cells might participate to the increased risk of herpes zoster infection in patients treated with tofacitinib and suggest to remains cautious about a possible increased risk of lymphoma. <h3>Disclosure of interest</h3> None declared
Magnesium degradation under physiological conditions – Best practice
Authors: Jorge Gonzalez, Rui Qing Hou, Eshwara P.S. Nidadavolu, Regine Willumeit-Römer, Frank Feyerabend
Journal: Bioactive Materials (2018)

This review focusses on the application of physiological conditions for the mechanistic understanding of magnesium degradation. Despite the undisputed relevance of simplified laboratory setups for alloy screening purposes, realistic and predictive in vitro setups are needed. Due to the complexity of these systems, the review gives an overview about technical measures, defines some caveats and can be used as a guideline for the establishment of harmonized laboratory approaches.
Does CVS–Aetna Spell the End of Business as Usual?
Authors: Leemore S Dafny
Journal: New England Journal of Medicine (2018)

Interview with Dr. Leemore Dafny on the proposed merger of CVS and Aetna. (07:08)Download The proposed $70 billion deal between CVS and Aetna would be a vertical merger that could heighten competition. By offering a new value proposition, the new company would aim to stay relevant despite encroachment by e-tailers and reduce total spending for care.
Diploma in Practical Palliative Care
Authors: Kate Hodgson
Journal: BMJ (2008)

BACKGROUND--In asthmatic subjects bronchoconstriction is induced by inhalation of the common food preservatives sulphur dioxide (SO2) and metabisulphite (MBS). SO2 and MBS challenges share many similarities, but it is not known whether they are equivalent. In this study of subjects with mild clinical asthma equivalence was assessed by comparing SO2 and MBS reactivity by estimating the total dose of SO2 inhaled during SO2 and MBS challenges, and by calculating SO2 uptake during both challenges. In addition, as the MBS solutions inhaled were acidic and hyperosmolar, the effect of these factors on MBS responsiveness was investigated. METHODS--Fifteen subjects were challenged on separate days with doubling (0.5 to 8.0 ppm) concentrations of SO2 gas inhaled during three minute periods of isocapnic hyperventilation and MBS administered in doses ranging from 0.1 to 12.8 mumol using the Wright protocol. On two other days SO2 and MBS challenges were preceded by a challenge with phosphate buffered saline (PBS) solutions of pH and osmolarity similar to MBS solutions. Response was measured as the dose or concentration causing a 20% fall in FEV1 (PD20 or PC20). RESULTS--All subjects reacted to MBS and 14 responded to SO2. Geometric mean histamine PD20 was 1.61 mumol (95% confidence interval 0.72 to 3.60). MBS and SO2 airway responsiveness were not significantly related. Estimates of the mean concentration of SO2 inhaled during SO2 and MBS challenges differed, as did estimates of the mean SO2 uptake during both challenges. MBS and SO2 reactivity were not affected by prior challenge with PBS solutions. CONCLUSIONS--SO2 and MBS challenges are not comparable. MBS reactivity was not affected by the hyperosmolar, acidic nature of its solutions.
Associate specialist grade should be reopened, demand SAS doctors
Authors: Helen Jaques
Journal: BMJ (2012)

The associate specialist grade, closed to new applicants in 2008, should be reopened under national terms and conditions of services, doctors in the staff, associate specialist, and specialty (SAS) grade have demanded.

Delegates at the BMA’s annual SAS doctors conference also agreed that BMA negotiators had been “grossly negligent” in allowing the closure of the associate specialist grade when renegotiating the …
LONG-TERM FOLLOW UP OF ACUTE HEART FAILURE PATIENTS UNDERWENT LEVOSIMENDAN INFUSION: IDENTIFICATION OF RESPONDERS AND NON-RESPONDERS BY USING HLM CLASSIFICATION
Authors: Maria Alfarano, Paolo Severino, Ilaria Mancini, Mariateresa Pucci, Elisa Pagliaroli, Martina Straito, Ilaria Ferrari, Stefano Peroni, Simone Calcagno, Antonio Fusto, Massimo Mancone, Francesco Fedele
Journal: Journal of the American College of Cardiology (2018)
Soft‐tissue augmentation procedures in edentulous esthetic areas
Authors: Matteo Marzadori, Martina Stefanini, Claudio Mazzotti, Sabrina Ganz, Praveen Sharma, Giovanni Zucchelli
Journal: Periodontology 2000 (2018)

Abstract Loss of dentition leads to functional and esthetic challenges that are determined by the anatomic features of the edentulous area. These features can complicate the prosthetic rehabilitation of such patients, especially in situations where optimal esthetic outcomes are desired. For these reasons, reconstructive plastic surgery procedures, aimed at restoring the alveolar ridge to its former dimensions, have become of great clinical interest. These reconstructive plastic surgery procedures frequently involve soft‐tissue augmentation, performed to improve the quality and quantity of mucogingival tissue with the aim to achieve an ideal esthetic result. This review will focus on the description and expected outcomes of different surgical techniques for soft‐tissue augmentation in edentulous areas, as described in the literature. Although more information from a larger number of studies and randomized controlled clinical trials is needed, it is possible to draw some conclusions, namely: pouch procedures are the first choice for soft‐tissue augmentation, especially in high‐demand esthetic areas; roll techniques are possible in shallow buccolingual soft‐tissue augmentations; and onlay, inlay and combination grafts are less suitable for soft‐tissue augmentation because of their poor esthetic results.
COMPARING RESOURCE UTILIZATION AMONG PEDIATRIC HEART TRANSPLANT INDICATIONS USING A NOVEL, MERGED DATA SET FROM THE UNITED NETWORK FOR ORGAN SHARING AND THE PEDIATRIC HEALTH INFORMATION SYSTEMS (UNOS-PHIS) DATABASES
Authors: Danielle Burstein, Yimei Li, Kelly D. Getz, Yuan-Shung Huang, Joseph William Rossano, Matthew O'Connor, Kimberly Lin, Richard Aplenc
Journal: Journal of the American College of Cardiology (2018)
Address competing tensions in emergency medicine training, say researchers
Authors: Matthew Limb
Journal: BMJ (2016)

Emergency medicine placements are invaluable for trainee doctors’ learning but the “competing tensions” that stem from delivering services have to be tackled, say researchers.

Trainees need adequate levels of supervision and support and there should be agreement over the “boundaries of risk” that they are exposed to, a team from Sheffield University’s School of Health and Related Research have said.

The researchers carried out an in depth study of emergency department training from both teachers’ and trainees’ perspectives.1 The study analysed the impact on foundation year 2 (FY2) doctors’ performance and …
Antibiotic-loaded nanoparticles targeted to the site of infection enhance antibacterial efficacy
Authors: Sazid Hussain, Jinmyoung Joo, Jinyoung Kang, Byungji Kim, Gary B. Braun, Zhi-Gang She, Dokyoung Kim, Aman P. Mann, Tarmo Mölder, Tambet Teesalu, Santina Carnazza, Salvatore Guglielmino, Michael J. Sailor, Erkki Ruoslahti
Journal: Nature Biomedical Engineering (2018)
EFFICACY AND MORTALITY USING ROTATING CUTTING SHEATHS VERSUS LASER SHEATHS FOR TRANSVENOUS LEAD EXTRACTION: A META-ANALYSIS
Authors: Sun Yong Lee, Xiaofan Guo, Ricardo Cardona, Celso Diaz, Cara Pellegrini, Ramin Beygui, Gregory M. Marcus, Byron K. Lee
Journal: Journal of the American College of Cardiology (2018)
Clinical bacteriology in low-resource settings: today's solutions
Authors: Sien Ombelet, Jean-Baptiste Ronat, Timothy Walsh, Cedric P Yansouni, Janneke Cox, Erika Vlieghe, Delphine Martiny, Makeda Semret, Olivier Vandenberg, Jan Jacobs, Octavie LUNGUYA, Marie-France PHOBA, Palpouguini LOMPO, Thong PHE, Samuel KARIUKI, Paul N NEWTON, David A B DANCE, Claude MUVUNYI, Sayda EL SAFI, Barbara BARBE, Dadi FALAY, Dissou AFFOLABI, Maurice PAGE, Céline LANGENDORF, Yves GILLE, Tjalling LEENSTRA, John STELLING, Thierry NAAS, Thomas KESTEMAN, Daniel SEIFU, Elisabeth DELAROCQUE-ASTAGNEAU, Constance SCHULTSZ, Heidi SCHUTT-GEROWITT, Joanne LETCHFORD, Heiman WERTHEIM, Gunnar KAHLMETER, Awa AIDARA KANE
Journal: The Lancet Infectious Diseases (2018)
Use of BMI as the marker of adiposity in a metabolic syndrome severity score: Derivation and validation in predicting long-term disease outcomes
Authors: Matthew J Gurka, Stephanie L Filipp, Solomon K Musani, Mario Sims, Mark D DeBoer
Journal: Metabolism (2018)

Estimates of adiposity in evaluating the metabolic syndrome (MetS) have traditionally utilized measures of waist circumference (WC), whereas body mass index (BMI) is more commonly used clinically. Our objective was to determine if a MetS severity Z-score employing BMI as its measure of adiposity (MetS-Z-BMI) would perform similarly to a WC-based score (MetS-Z-WC) in predicting future disease.