tbuckley/cabot-search huggingface dataset:
Differential diagnosis between newly diagnosed asthma and COPD using exhaled breath condensate metabolomics: a pilot study
Authors: Mauro Maniscalco, Debora Paris, Dominique J. Melck, Antonio Molino, Mauro Carone, Paolo Ruggeri, Gaetano Caramori, Andrea Motta
Journal: European Respiratory Journal (2018)

Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous diseases with high pathological burden and healthcare costs [1–3]. In outpatient clinical practice, an accurate differential diagnosis is often very difficult, particularly in adult smokers, requiring specific lung function tests [4, 5]. Since nuclear magnetic resonance (NMR)-based metabolomics of exhaled breath condensate (EBC) discriminates adults with COPD [6–8] or asthma [9] from healthy subjects, we hypothesised that it is also able to differentiate asthma and COPD patients of different severities. NMR profiling of EBC discriminates between asthma and COPD and this may help clinicians with differential diagnosis <http://ow.ly/cNGI30hWYAE>
I am a third year resident in general surgery in Thessaloniki, Greece. After completing my six year training in general surgery I am interested in training in a more specialised field of general surgery (for example, breast or colorectal surgery). What route should I follow? What sort of position should I apply for? What are the requirements?
Authors: Faisal Hanif
Journal: BMJ (2005)

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>
GP indemnity fees rise by 25% in a year, survey finds
Authors: Abi Rimmer
Journal: BMJ (2015)

Indemnity fees for GPs have risen by 25% in a year, the results of a small survey by the Family Doctor Association have shown.

The organisation sent a snapshot survey to 1000 GPs and received 96 responses. It found that, on average, GPs were paying indemnity fees of £1132 a year for each four hour session that they worked each week. This was a 25% increase on 2014, when GPs paid £869 a session, the association …
Higher Absolute Lymphocyte Counts Predict Lower Mortality from Early-Stage Triple-Negative Breast Cancer
Authors: Anosheh Afghahi, Natasha Purington, Summer S. Han, Manisha Desai, Emma Pierson, Maya B. Mathur, Tina Seto, Caroline A. Thompson, Joseph Rigdon, Melinda L. Telli, Sunil S. Badve, Christina N. Curtis, Robert B. West, Kathleen Horst, Scarlett L. Gomez, James M. Ford, George W. Sledge, Allison W. Kurian
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Tumor-infiltrating lymphocytes (TIL) in pretreatment biopsies are associated with improved survival in triple-negative breast cancer (TNBC). We investigated whether higher peripheral lymphocyte counts are associated with lower breast cancer–specific mortality (BCM) and overall mortality (OM) in TNBC. Experimental Design: Data on treatments and diagnostic tests from electronic medical records of two health care systems were linked with demographic, clinical, pathologic, and mortality data from the California Cancer Registry. Multivariable regression models adjusted for age, race/ethnicity, socioeconomic status, cancer stage, grade, neoadjuvant/adjuvant chemotherapy use, radiotherapy use, and germline BRCA1/2 mutations were used to evaluate associations between absolute lymphocyte count (ALC), BCM, and OM. For a subgroup with TIL data available, we explored the relationship between TILs and peripheral lymphocyte counts. Results: A total of 1,463 stage I–III TNBC patients were diagnosed from 2000 to 2014; 1,113 (76%) received neoadjuvant/adjuvant chemotherapy within 1 year of diagnosis. Of 759 patients with available ALC data, 481 (63.4%) were ever lymphopenic (minimum ALC &amp;lt;1.0 K/μL). On multivariable analysis, higher minimum ALC, but not absolute neutrophil count, predicted lower OM [HR = 0.23; 95% confidence interval (CI), 0.16–0.35] and BCM (HR = 0.19; CI, 0.11–0.34). Five-year probability of BCM was 15% for patients who were ever lymphopenic versus 4% for those who were not. An exploratory analysis (n = 70) showed a significant association between TILs and higher peripheral lymphocyte counts during neoadjuvant chemotherapy. Conclusions: Higher peripheral lymphocyte counts predicted lower mortality from early-stage, potentially curable TNBC, suggesting that immune function may enhance the effectiveness of early TNBC treatment. Clin Cancer Res; 24(12); 2851–8. ©2018 AACR.
FIFTEEN YEARS OF TRANSCATHETER AORTIC VALVE IMPLANTATION: A PROSPECTIVE ANALYSIS OF A PIONEER CENTER - LONG TERM SURVIVAL AND VALVE DURABILITY
Authors: Guillaume Avinee, Eric Durand, Christophe Tron, Anastasia Sokoloff, Thibaut Hemery, Pierre-Yves Litzler, G. Alain Cribier, Helene Eltchaninoff
Journal: Journal of the American College of Cardiology (2018)
Ibrutinib versus temsirolimus: 3-year follow-up of patients with previously treated mantle cell lymphoma from the phase 3, international, randomized, open-label RAY study
Authors: S Rule, W Jurczak, M Jerkeman, C Rusconi, M Trneny, F Offner, D Caballero, C Joao, M Witzens-Harig, G Hess, I Bence-Bruckler, S-G Cho, C Thieblemont, W Zhou, T Henninger, J Goldberg, J Vermeulen, M Dreyling
Journal: Leukemia (2018)
RNA-dependent chromatin targeting of TET2 for endogenous retrovirus control in pluripotent stem cells
Authors: Diana Guallar, Xianju Bi, Jose Angel Pardavila, Xin Huang, Carmen Saenz, Xianle Shi, Hongwei Zhou, Francesco Faiola, Junjun Ding, Phensinee Haruehanroengra, Fan Yang, Dan Li, Carlos Sanchez-Priego, Arven Saunders, Feng Pan, Victor Julian Valdes, Kevin Kelley, Miguel G. Blanco, Lingyi Chen, Huayan Wang, Jia Sheng, Mingjiang Xu, Miguel Fidalgo, Xiaohua Shen, Jianlong Wang
Journal: Nature Genetics (2018)
GastroPET: Phase II academic clinical trial evaluating sequential FDG-PET driven preoperative treatment strategy in locally advanced oesophago-gastric cancer in the context of miRNA- and immune-based biomarkers.
Authors: Radka Obermannova, Renata Hejnova, Lenka Zdrazilova-Dubska, Regina Demlova, Ondrej Slaby, Hana Studentova, Lubos Petruzelka, Peter Grell, Rostislav Vyzula
Journal: Journal of Clinical Oncology (2018)

TPS202 Background: The standard treatment approach in locally advanced oesophago-gastric cancer (OGC) contains surgery with perioperative chemotherapy (CXT). Nonetheless according to sequential 18 FDG-PET-CT only 40–50% of the patients respond to CTX and non-responding patients would perhaps profit from concurrent radiotherapy (CRT). This phase II trial evaluates the sequential FDG-PET driven preoperative treatment strategy of early histopathological response and improved survival. Methods: Approximately 70 pts with resectable locally advanced OGC will be enrolled in this interventional, prospective, non-randomized multicenter trial. Pts will undergo baseline FDG-PET scan and will be given 1 cycle of CXT (FLOT or FOLFOX). FDG-PET scan will be repeated after 14 days and FDG-PET responders with ≥ 35% reduction in SUV max from baseline to initial treatment will continue with CXT prior to surgery. FDG-PET non-responders will switch to the CRT (weekly carboplatin and paclitaxel with concurrent radiotherapy (45 Gy in 25 fractions) prior to surgery. The main goal of the surgical therapy is to obtain negative surgical margins. Selected miRNAs and immune parameters will be evaluated for their predictive value. Eligibility: biopsy-proven locally advanced resectable oesophago-gastric adenocarcinoma (Siewert I – III) stage Ib – IIIc; endoscopy and endoscopic ultrasound; pts to be fit for the platinum-containing CXT; potentially R0 resectable tumors. The primary objective: the predictive value of FDG-PET dynamics in the preoperative setting for early regression and R0 resection rate. Secondary endpoints: i/ identification of tissue/plasma miRNA and immune-based biomarkers, ii/ disease free survival and overall survival. Status: Opened to accrual in Oct 2017. Clinical trial information: Eudra CT 2017-001264-38. This work was supported by Ministry of Health, Project No: 15 P03-17-29389A and projects LO1413, DRO and LM15089 BBMRI-CZ. Clinical trial information: 2017-001264-38.
Medical registrars’ increasing workload threatens training quality and patient care
Authors: Caroline White
Journal: BMJ (2013)

Medical registrars are struggling to cope with “unmanageable” workloads, jeopardising the safety of patients and the quality of hospital care and compromising training, the Royal College of Physicians has warned.1

Hospitals cannot afford to let the situation deteriorate any further, concludes a report from the college on the future of the hospital workforce. The report draws on evidence gathered in 2011-12 from online surveys and face to face interviews with 2800 medical registrars (doctors in the later stages of training to become consultants and who specialise in hospital medicine rather than general practice or surgery) in England.

Hospitals are too reliant on medical registrars to provide the bulk of hospital services, particularly at night, the report says. More than one in …
PREDICTING MORTALITY WITH AORTOMITRAL CALCIFICATIONS IN 317 TAVR PATIENTS
Authors: Martin Willemink, Eva Maret, Kegan Moneghetti, Juyong Kim, Francois Haddad, Yukari Kobayashi, Kai Higashigaito, Alan Yeung, Anson Lee, D. Craig Miller, Michael Fischbein, William Fearon, Dominik Fleischmann
Journal: Journal of the American College of Cardiology (2018)
LncRNA <i>ZFAS1</i> as a SERCA2a Inhibitor to Cause Intracellular Ca <sup>2+</sup> Overload and Contractile Dysfunction in a Mouse Model of Myocardial Infarction
Authors: Ying Zhang, Lei Jiao, Lihua Sun, Yanru Li, Yuqiu Gao, Chaoqian Xu, Yingchun Shao, Mengmeng Li, Chunyan Li, Yanjie Lu, Zhenwei Pan, Lina Xuan, Yiyuan Zhang, Qingqi Li, Rui Yang, Yuting Zhuang, Yong Zhang, Baofeng Yang
Journal: Circulation Research (2018)

Ca2+ homeostasis-a critical determinant of cardiac contractile function-is critically regulated by SERCA2a (sarcoplasmic reticulum Ca2+-ATPase 2a). Our previous study has identified ZFAS1 as a new lncRNA biomarker of acute myocardial infarction (MI). To evaluate the effects of ZFAS1 on SERCA2a and the associated Ca2+ homeostasis and cardiac contractile function in the setting of MI. ZFAS1 expression was robustly increased in cytoplasm and sarcoplasmic reticulum in a mouse model of MI and a cellular model of hypoxia. Knockdown of endogenous ZFAS1 by virus-mediated silencing shRNA partially abrogated the ischemia-induced contractile dysfunction. Overexpression of ZFAS1 in otherwise normal mice created similar impairment of cardiac function as that observed in MI mice. Moreover, at the cellular level, ZFAS1 overexpression weakened the contractility of cardiac muscles. At the subcellular level, ZFAS1 deleteriously altered the Ca2+ transient leading to intracellular Ca2+ overload in cardiomyocytes. At the molecular level, ZFAS1 was found to directly bind SERCA2a protein and to limit its activity, as well as to repress its expression. The effects of ZFAS1 were readily reversible on knockdown of this lncRNA. Notably, a sequence domain of ZFAS1 gene that is conserved across species mimicked the effects of the full-length ZFAS1. Mutation of this domain or application of an antisense fragment to this conserved region efficiently canceled out the deleterious actions of ZFAS1. ZFAS1 had no significant effects on other Ca2+-handling regulatory proteins. ZFAS1 is an endogenous SERCA2a inhibitor, acting by binding to SERCA2a protein to limit its intracellular level and inhibit its activity, and a contributor to the impairment of cardiac contractile function in MI. Therefore, anti-ZFAS1 might be considered as a new therapeutic strategy for preserving SERCA2a activity and cardiac function under pathological conditions of the heart.
With regard to the new immigration rule changes, my current position is that I am an SHO applying for SpR rotations with an HSMP visa, Each trust and deanery has its own interpretations of this visa. What chances do I have of being shortlisted?
Authors: Sunder Raj Gopaul
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>
SIZE, EJECTION FRACTION AND LONGITUDINAL STRAIN ANALYSES TO ASSESS REMODELING IN ALL 4 CARDIAC CHAMBERS FOLLOWING TRANSCATHETER AORTIC VALVE REPLACEMENT
Authors: Diego Medvedofsky, Tatsuya Miyoshi, Toby Rogers, Linzhi Xu, Itsik Ben-Dor, Lowell Satler, Rebecca Torguson, Ron Waksman, Federico Asch
Journal: Journal of the American College of Cardiology (2018)
Estimating Acute Cardiovascular Effects of Ambient PM2.5 Metals
Authors: Dongni Ye, Mitchel Klein, James A. Mulholland, Armistead G. Russell, Rodney Weber, Eric S. Edgerton, Howard H. Chang, Jeremy A. Sarnat, Paige E. Tolbert, Stefanie Ebelt Sarnat
Journal: Environmental Health Perspectives (2018)

Background: Few epidemiologic studies have investigated health effects of water-soluble fractions of PM2.5 metals, the more biologically accessible fractions of metals, in their attempt to identify health-relevant components of ambient PM2.5. Objectives: In this study, we estimated acute cardiovascular effects of PM2.5 components in an urban population, including a suite of water-soluble metals that are not routinely measured at the ambient level. Methods: Ambient concentrations of criteria gases, PM2.5, and PM2.5 components were measured at a central monitor in Atlanta, Georgia, during 1998–2013, with some PM2.5 components only measured during 2008–2013. In a time-series framework using Poisson regression, we estimated associations between these pollutants and daily counts of emergency department (ED) visits for cardiovascular diseases in the five-county Atlanta area. Results: Among the PM2.5 components we examined during 1998–2013, water-soluble iron had the strongest estimated effect on cardiovascular outcomes [RR̂=1.012 (95% CI: 1.005, 1.019), per interquartile range increase (20.46ng/m3)]. The associations for PM2.5 and other PM2.5 components were consistent with the null when controlling for water-soluble iron. Among PM2.5 components that were only measured during 2008–2013, water-soluble vanadium was associated with cardiovascular ED visits [RR̂=1.012 (95% CI: 1.000, 1.025), per interquartile range increase (0.19ng/m3)]. Conclusions: Our study suggests cardiovascular effects of certain water-soluble metals, particularly water-soluble iron. The observed associations with water-soluble iron may also point to certain aspects of traffic pollution, when processed by acidifying sulfate, as a mixture harmful for cardiovascular health. https://doi.org/10.1289/EHP2182
Intergroup study EORTC-1333-GUCG: A randomized multicenter phase III trial comparing enzalutamide vs. a combination of Ra223 and enzalutamide in asymptomatic or mildly symptomatic castration resistant prostate cancer (CRPC) patients metastatic to bone (PEACE III).
Authors: Bertrand F. Tombal, Yohann Loriot, Fred Saad, Raymond S. McDermott, Sandrine Marreaud, Laurence Collette, Silke Gillessen
Journal: Journal of Clinical Oncology (2018)

TPS390 Background: α-emitting radiopharmaceutical Ra-223 reduces the risk of death by 30% vs placebo in phase 3 ALSYMPCA (Parker et al. NEJM 2013). Ra-223’s favourable safety profile and lack of significant toxicity support combining it with other agents. The ALSYMPCA trial was developed to add Ra-223 on the contemporary standard of care that did not include last generation AR pathway inhibitors enzalutamide, one of the modern reference treatments for asymptomatic or moderately symptomatic metastatic CRPC (Gillessen et al. Eur Urol. 2017). In addition Ra-223 is registered in symptomatic prostate cancer (PCa), a very late stage of modern patient disease. There is thus a good rationale to combine Ra-223 to modern AR pathway inhibitors and to initiate the treatment in asymptomatic or moderately symptomatic patients. Methods: The EORTC 1333-GUCG study will run in 51 sites (21 activated) across 7 European countries, 4 sites in US and 12 sites in Canada. The study is an intergroup initiative between EORTC (Coordinating Group), UNICANCER; Cancer Trials Ireland (Ireland), ACCRU (The United States), and CUOG (Canada). A total of 560 patients will be randomized in a 1:1 ratio to receive enzalutamide 160 mg q.d. p.o. or enzalutamide at the same dose and Ra223 at 55 kBq/kg i.v. monthly for 6 months. Patients will be stratified by country, pain (BPI 0-1 vs BPI 2-3), prior docetaxel use (no vs yes) and use of bone targeting agents (no vs yes). The main inclusion criteria require asymptomatic or mildly symptomatic (defined as no opioids and BPI-SF question 3 &lt; 4), metastatic to bone with ≥ 2 bone metastases with or without additional lymph node metastases. Visceral metastases are not allowed. The primary endpoint is radiological progression-free survival (rPFS1), according to PCWG3. Secondary endpoints include: overall survival, PCa specific survival, 1 st symptomatic skeletal event (SSE), time to initiation of next systemic anti-neoplastic therapy, time to pain progression, health-related quality of life (EQ-5D-5L and BPI). Clinical trial information: NCT02194842.
IMMUNE PROFILE OF HEALTHY CARDIOVASCULAR AGING: INSIGHTS FROM A POPULATION-BASED STUDY AND NETWORK MODELING
Authors: Sara Bouajila, Kegan Moneghetti, Yukari Kobayashi, Fatemeh A. Gomari, Fahim Abbasi, Mark M. Davis, Joseph C. Wu, Tatiana Kuznetsova, Nazish Sayed, Francois Haddad
Journal: Journal of the American College of Cardiology (2018)
The altered expression of Paraoxonase 1 in the gastric carcinoma.
Authors: Sung Soo Kim, Jin Soo Kim
Journal: Journal of Clinical Oncology (2018)

94 Background: High doses inadequate removal of reactive oxygen species result in oxidative stress, which may cause severe metabolic malfunctions and damage to biological molecules including DNA An elevated oxidative status has been found in many types of cancer cells and helicobacter infection. Paraoxonase 1 is one of the endogenous free radical scavenging systems in the human and believed to be involved in the protection against oxidative stress. It has been reported that serum levels of Paraoxonase 1 were lower in patients with pancreatic or gastric cancer than in healthy controls. But there was no study about differential Paraoxonase 1 expression in gastric cancer tissue compared to adjacent non-tumor tissue. In this study, we investigated the changes of Paraoxonase 1 expression in the helicobacter pylori infection and gastric cancer. Methods: 109 gastric cancer tissues and 109 adjacent non-tumor tissues were obtained from 109 patients who received gastrectomy for curative resection. Eighteen H. pylori-positive patients who successfully eradicated were involved. Expression of Paraoxonase 1 and Malondialdehyde was assessed by immunohistochemistry using a tissue microarray method. Results: The intensity of immunohistochemical stain on Malondialdehyde and Paraoxonase 1 was significantly elevated in pre-eradication state compared to post-eradication (1.77 vs 1.05, 1.83 vs 1.11, P&lt; 0.05) of helicobacter infection. The intensity of Malondialdehyde was significantly elevated in gastric carcinoma than adjacent non-tumor area (1.22 vs 0.39, P&lt; 0.05). But intensity of Paraoxonase 1 showed no significant difference in both area (0.55 vs 0.68, P&gt; 0.05). Conclusions: Paraoxonase 1 may be one of antioxidant enzyme in H. pylori induced gastritis. In the gastric carcinoma, it’s role may need further study to conclude.
INITIAL STROKE SEVERITY IS A CRUCIAL PREDICTOR FOR HEMORRHAGIC STROKE- AND ISCHEMIC STROKE-RELATED MORTALITY
Authors: Mark Alberts, Jennifer H. Lin, Yen-Wen Chen, Emily Kogan, Kathryn Twyman, Siddhant Deshmukh, Dejan Milentijevic
Journal: Journal of the American College of Cardiology (2018)
The <scp>IL</scp>‐13/periostin/<scp>IL</scp>‐24 pathway causes epidermal barrier dysfunction in allergic skin inflammation
Authors: Y. Mitamura, S. Nunomura, Y. Nanri, M. Ogawa, T. Yoshihara, M. Masuoka, G. Tsuji, T. Nakahara, A. Hashimoto‐Hachiya, S. J. Conway, M. Furue, K. Izuhara
Journal: Allergy (2018)

Barrier dysfunction is an important feature of atopic dermatitis (AD) in which IL-4 and IL-13, signature type 2 cytokines, are involved. Periostin, a matricellular protein induced by IL-4 or IL-13, plays a crucial role in the onset of allergic skin inflammation, including barrier dysfunction. However, it remains elusive how periostin causes barrier dysfunction downstream of the IL-13 signal.We systematically identified periostin-dependent expression profile using DNA microarrays. We then investigated whether IL-24 downregulates filaggrin expression downstream of the IL-13 signals and whether IL-13-induced IL-24 expression and IL-24-induced downregulation of filaggrin expression are dependent on the JAK/STAT pathway. To build on the significance of in vitro findings, we investigated expression of IL-24 and activation of STAT3 in mite-treated mice and in AD patients.We identified IL-24 as an IL-13-induced molecule in a periostin-dependent manner. Keratinocytes are the main IL-24-producing tissue-resident cells stimulated by IL-13 in a periostin-dependent manner via STAT6. IL-24 significantly downregulated filaggrin expression via STAT3, contributing to barrier dysfunction downstream of the IL-13/periostin pathway. Wild-type mite-treated mice showed significantly enhanced expression of IL-24 and activation of STAT3 in the epidermis, which disappeared in both STAT6-deficient and periostin-deficient mice, suggesting that these events are downstream of both STAT6 and periostin. Moreover, IL-24 expression was enhanced in the epidermis of skin tissues taken from AD patients.The IL-13/periostin pathway induces IL-24 production in keratinocytes, playing an important role in barrier dysfunction in AD.