tbuckley/cabot-search huggingface dataset:
Prospective analysis of 4,474 prostate biopsies to evaluate potential treatment management impact of combined clinical-genomic risk classification.
Authors: Paul L. Nguyen, Jingbin Zhang, Kasra Yousefi, Elai Davicioni, Robert Benjamin Den, Felix Y Feng, Daniel Eidelberg Spratt
Journal: Journal of Clinical Oncology (2018)

39 Background: Prior studies suggested integrated clinical-genomic risk grouping can more accurately prognosticate prostate cancer (PCa) outcome than NCCN clinical risk. We evaluated the potential for genomic testing to reclassify patients in a manner that could change management compared to NCCN risk groups. Methods: We evaluated 4,474 consecutive patients with PCa who received the Decipher Biopsy test between 01/2016-08/2017 and had information to determine NCCN risk. Genomic categorizations with the potential to change management were defined as NCCN very low/low to genomic intermediate or high (active surveillance to active treatment), NCCN favorable intermediate to genomic high (radiation therapy [RT] alone to RT plus androgen deprivation therapy [ADT]), NCCN unfavorable intermediate to genomic low (RT + ADT to RT alone), NCCN high risk to genomic low (RT + long term ADT to RT + short term ADT). Results: There were 927 NCCN low-risk, 2,427 intermediate, and 1,120 high-risk patients. Among NCCN low-risk, the incidence of genomic low, intermediate, and high risk was 58.7%, 25.0%, and 16.3% respectively, for NCCN intermediate it was 36.5%, 27.6%, and 35.8%, and for NCCN high risk it was 15.9%, 17.1%, and 67.1%. Management could have been changed in the 41.3% of NCCN low risk patients with intermediate or high genomic risk, 26.7% of favorable intermediate risk patients who had high genomic risk, 32.4% of unfavorable intermediate risk patients with low genomic risk, and 15.9% of high risk patients with low genomic risk. Conclusions: A slight majority (54%) of Decipher Biopsy users have NCCN intermediate-risk disease, likely reflecting a need for further prognostic information to refine recommendations in intermediate risk. Reclassification of NCCN groups by genomic risk was common and an integrated clinical-genomic risk system could have altered treatment recommendations in 41.3% of NCCN low, 26.7% of favorable intermediate, 32.4% of unfavorable intermediate risk, and 15.9% of high risk patients.
Robot-assisted minimally invasive thoraco-laparoscopic esophagectomy versus open transthoracic esophagectomy for resectable esophageal cancer: A randomized controlled trial.
Authors: Pieter Christiaan Van Der Sluis, Sylvia van der Horst, Anne Maria May, Carlo Schippers, Lodewijk Brosens, Wouter van Dijk, Hans Joore, Christiaan Kroese, Nadia Haj Mohammad, Stella Mook, Frank P. Vleggaar, Inne Borel Rinkes, Jelle Ruurda, Richard van Hillegersberg
Journal: Journal of Clinical Oncology (2018)

6 Background: The standard curative treatment for patients with esophageal cancer is perioperative chemotherapy or preoperative chemoradiotherapy followed by open transthoracic esophagectomy (OTE). Robot-assisted minimally invasive thoraco-laparoscopic esophagectomy (RAMIE) may reduce perioperative complications and improve functional recovery. Methods: In this randomized controlled trial, 112 patients with resectable intrathoracic esophageal cancer were randomly assigned to RAMIE or OTE. The composite primary endpoint was the occurrence of overall postoperative complications (modified Clavien–Dindo classification (MCDC) grade 2-5). Results: Postoperative complications occurred less frequently after RAMIE (59%) compared to OTE (80%) (RR 0.74 (0.57-0.96; P = 0.02). RAMIE resulted in a less median blood loss (400ml versus 568ml, P &lt; 0.001), a lower percentage of surgery-related complications (RR 0.74 (0.57-0.96; P = 0.02), pulmonary complications (RR 0.54 (0.34-0.85; P = 0.005) and cardiac complications (RR 0.47 (0.27-0.83; P = 0.006)) and lower mean postoperative pain (visual analogue scale, 1.86 versus 2.62; p &lt; 0.000) compared to OTE. Functional recovery at postoperative day 14 was better in the RAMIE group (RR 1.48 (1.03–2.13; P = 0.038)) with better quality of life score at discharge (mean difference quality of life score 13.4 (2.0-24.7, p = 0.02) and 6 weeks post-discharge (mean difference 11.1 quality of life score (1.0-21.1; p = 0.03)). Mean costs for RAMIE were €34.892 and mean costs for OTE were €39.463 (p = 0.07). Oncological outcomes at short term (radicality, number of lymph nodes) and long term (overall and disease-free survival) were equal at a medium follow up of 38 months. Conclusions: RAMIE resulted in a lower percentage of overall, surgery-related and (cardio)pulmonary complications with lower postoperative pain, better quality of life and a better short term postoperative functional recovery compared to OTE. Oncological outcomes were equal. This randomized controlled trial provides evidence for the use of RAMIE to improve postoperative outcome in patients with resectable esophageal cancer. Clinical trial information: NCT01544790.
INFLUENCE OF FLOW AND VELOCITY PROFILE ON INCONSISTENCY IN ECHOCARDIOGRAPHIC AORTIC VALVE STENOSIS ASSESSMENT: A COMPUTED TOMOGRAPHY AND COMPUTATIONAL FLOW DYNAMICS STUDY
Authors: Tarun Mittal, Ed Nicol, Luise Reichmuth, Manish Jain, Aigul Baltabaeva, Shelley Rahman-Haley, Tito Kabir, Vasileios Panoulas, Saeed Mirsadraee, Miles Dalby, Quan Long
Journal: Journal of the American College of Cardiology (2018)
Targeting the SphK1/S1P/S1PR1 Axis That Links Obesity, Chronic Inflammation, and Breast Cancer Metastasis
Authors: Masayuki Nagahashi, Akimitsu Yamada, Eriko Katsuta, Tomoyoshi Aoyagi, Wei-Ching Huang, Krista P. Terracina, Nitai C. Hait, Jeremy C. Allegood, Junko Tsuchida, Kizuki Yuza, Masato Nakajima, Manabu Abe, Kenji Sakimura, Sheldon Milstien, Toshifumi Wakai, Sarah Spiegel, Kazuaki Takabe
Journal: Cancer Research (2018)

Although obesity with associated inflammation is now recognized as a risk factor for breast cancer and distant metastases, the functional basis for these connections remain poorly understood. Here, we show that in breast cancer patients and in animal breast cancer models, obesity is a sufficient cause for increased expression of the bioactive sphingolipid mediator sphingosine-1-phosphate (S1P), which mediates cancer pathogenesis. A high-fat diet was sufficient to upregulate expression of sphingosine kinase 1 (SphK1), the enzyme that produces S1P, along with its receptor S1PR1 in syngeneic and spontaneous breast tumors. Targeting the SphK1/S1P/S1PR1 axis with FTY720/fingolimod attenuated key proinflammatory cytokines, macrophage infiltration, and tumor progression induced by obesity. S1P produced in the lung premetastatic niche by tumor-induced SphK1 increased macrophage recruitment into the lung and induced IL6 and signaling pathways important for lung metastatic colonization. Conversely, FTY720 suppressed IL6, macrophage infiltration, and S1P-mediated signaling pathways in the lung induced by a high-fat diet, and it dramatically reduced formation of metastatic foci. In tumor-bearing mice, FTY720 similarly reduced obesity-related inflammation, S1P signaling, and pulmonary metastasis, thereby prolonging survival. Taken together, our results establish a critical role for circulating S1P produced by tumors and the SphK1/S1P/S1PR1 axis in obesity-related inflammation, formation of lung metastatic niches, and breast cancer metastasis, with potential implications for prevention and treatment.Significance: These findings offer a preclinical proof of concept that signaling by a sphingolipid may be an effective target to prevent obesity-related breast cancer metastasis. Cancer Res; 78(7); 1713-25. ©2018 AACR.
Genomic profiling reveals spatial intra-tumor heterogeneity in follicular lymphoma
Authors: Shamzah Araf, Jun Wang, Koorosh Korfi, Celine Pangault, Eleni Kotsiou, Ana Rio-Machin, Tahrima Rahim, James Heward, Andrew Clear, Sameena Iqbal, Jeff K. Davies, Peter Johnson, Maria Calaminici, Silvia Montoto, Rebecca Auer, Claude Chelala, John G. Gribben, Trevor A. Graham, Thierry Fest, Jude Fitzgibbon, Jessica Okosun
Journal: Leukemia (2018)

We are indebted to the patients for donating
tumor specimens as part of this study. The authors thank the Centre de
Ressources Biologiques (CRB)-Sante of Rennes (BB-0033-00056) for
patient samples, Queen Mary University of London Genome Centre
for Illumina Miseq sequencing, and the support by the National
Institute for Health Research (NIHR) Biomedical Research Centre at
Guy’s and St Thomas’ NHS Foundation Trust and King’s College
London for Illumina Hiseq sequencing. The views expressed are
those of the authors and not necessarily those of the NHS, the NIHR,
or the Department of Health. This work was supported by grants
from the Kay Kendall Leukaemia Fund (KKL 757 awarded to J.O.),
Cancer Research UK (22742 awarded to J.O., 15968 awarded to J.F.,
Clinical Research Fellowship awarded to S.A.), Bloodwise through
funding of the Precision Medicine for Aggressive Lymphoma (PMAL)
consortium, Centre for Genomic Health, Queen Mary University
of London, Carte d’Identite des Tumeurs (CIT), Ligue National
contre le Cancer, Pole de biologie hospital universitaire de
Rennes, CRB-Sante of Rennes (BB-0033-00056), and CeVi/Carnot
program.
Interleukin-30/IL27p28 Shapes Prostate Cancer Stem-like Cell Behavior and Is Critical for Tumor Onset and Metastasization
Authors: Carlo Sorrentino, Stefania L. Ciummo, Giuseppe Cipollone, Sara Caputo, Matteo Bellone, Emma Di Carlo
Journal: Cancer Research (2018)

Abstract Prostate cancer stem-like cells (PCSLC) are believed to be responsible for prostate cancer onset and metastasis. Autocrine and microenvironmental signals dictate PCSLC behavior and patient outcome. In prostate cancer patients, IL30/IL27p28 has been linked with tumor progression, but the mechanisms underlying this link remain mostly elusive. Here, we asked whether IL30 may favor prostate cancer progression by conditioning PCSLCs and assessed the value of blocking IL30 to suppress tumor growth. IL30 was produced by PCSLCs in human and murine prostatic intraepithelial neoplasia and displayed significant autocrine and paracrine effects. PCSLC-derived IL30 supported PCSLC viability, self-renewal and tumorigenicity, expression of inflammatory mediators and growth factors, tumor immune evasion, and regulated chemokine and chemokine receptor genes, primarily via STAT1/STAT3 signaling. IL30 overproduction by PCSLCs promoted tumor onset and development associated with increased proliferation, vascularization, and myeloid cell recruitment. Furthermore, it promoted PCSLC dissemination to lymph nodes and bone marrow by upregulating the CXCR5/CXCL13 axis, and drove metastasis to lungs through the CXCR4/CXCL12 axis. These mechanisms were drastically hindered by IL30 knockdown or knockout in PCSLCs. Collectively, these results mark IL30 as a key driver of PCSLC behavior. Targeting IL30 signaling may be a potential therapeutic strategy against prostate cancer progression and recurrence. Significance: IL30 plays an important role in regulating prostate cancer stem-like cell behavior and metastatic potential, therefore targeting this cytokine could hamper prostate cancer progression or recurrence. Cancer Res; 78(10); 2654–68. ©2018 AACR.
Transgenerationally Precipitated Meiotic Chromosome Instability Fuels Rapid Karyotypic Evolution and Phenotypic Diversity in an Artificially Constructed Allotetraploid Wheat (AADD)
Authors: Xiaowan Gou, Yao Bian, Ai Zhang, Huakun Zhang, Bin Wang, Ruili Lv, Juzuo Li, Bo Zhu, Lei Gong, Bao Liu
Journal: Molecular Biology and Evolution (2018)

Although a distinct karyotype with defined chromosome number and structure characterizes each biological species, it is intrinsically labile. Polyploidy or whole-genome duplication has played a pervasive and ongoing role in the evolution of all eukaryotes, and is the most dramatic force known to cause rapid karyotypic reconfiguration, especially at the initial stage. However, issues concerning transgenerational propagation of karyotypic heterogeneity and its translation to phenotypic diversity in nascent allopolyploidy, at the population level, have yet to be studied in detail. Here, we report a large-scale examination of transgenerationally propagated karyotypic heterogeneity and its phenotypic manifestation in an artificially constructed allotetraploid with a genome composition of AADD, that is, involving two of the three progenitor genomes of polyploid wheat. Specifically, we show that 1) massive organismal karyotypic heterogeneity is precipitated after 12 consecutive generations of selfing from a single euploid founder individual, 2) there exist dramatic differences in aptitudes between subgenomes and among chromosomes for whole-chromosome gain and/or loss and structural variations, 3) majority of the numerical and structural chromosomal variations are concurrent due to mutual contingency and possible functional constraint, 4) purposed and continuous selection and propagation for euploidy over generations did not result in enhanced karyotype stabilization, and 5) extent of karyotypic variation correlates with variability of phenotypic manifestation. Together, our results document that allopolyploidization catalyzes rampant and transgenerationally heritable organismal karyotypic heterogeneity that drives population-level phenotypic diversification, which lends fresh empirical support to the still contentious notion that whole-genome duplication enhances organismal evolvability.
CLINICAL SIGNIFICANCE OF LIPID-RICH PLAQUE WITH INTACT FIBROUS CAP DEFINED BY OPTICAL COHERENCE TOMOGRAPHY IN ACUTE MYOCARDIAL INFARCTION
Authors: Masahiro Hoshino, Taishi Yonetsu, Yoshihisa Kanaji, Eisuke Usui, Hiroaki Ohya, Yohei Sumino, Rikuta Hamaya, Masahiro Hada, Tetsumin Lee, Tsunekazu Kakuta
Journal: Journal of the American College of Cardiology (2018)
Depression and Human Immunodeficiency Virus Infection Are Risk Factors for Incident Heart Failure Among Veterans
Authors: Jessica R. White, Chung-Chou H. Chang, Kaku A. So-Armah, Jesse C. Stewart, Samir K. Gupta, Adeel A. Butt, Cynthia L. Gibert, David Rimland, Maria C. Rodriguez-Barradas, David A. Leaf, Roger J. Bedimo, John S. Gottdiener, Willem J. Kop, Stephen S. Gottlieb, Matthew J. Budoff, Tasneem Khambaty, Hilary A. Tindle, Amy C. Justice, Matthew S. Freiberg
Journal: Circulation (2015)

Background— Both HIV and depression are associated with increased heart failure (HF) risk. Depression, a common comorbidity, may further increase the risk of HF among adults with HIV infection (HIV+). We assessed the association between HIV, depression, and incident HF. Methods and Results— Veterans Aging Cohort Study (VACS) participants free from cardiovascular disease at baseline (n=81 427: 26 908 HIV+, 54 519 without HIV [HIV−]) were categorized into 4 groups: HIV− without major depressive disorder (MDD) [reference], HIV− with MDD, HIV+ without MDD, and HIV+ with MDD. International Classification of Diseases, Ninth Revision codes from medical records were used to determine MDD and the primary outcome, HF. After 5.8 years of follow-up, HF rates per 1000 person-years were highest among HIV+ participants with MDD (9.32; 95% confidence interval [CI], 8.20–10.6). In Cox proportional hazards models, HIV+ participants with MDD had a significantly higher risk of HF (adjusted hazard ratio, 1.68; 95% CI, 1.45–1.95) compared with HIV− participants without MDD. MDD was associated with HF in separate fully adjusted models for HIV− and HIV+ participants (adjusted hazard ratio, 1.21; 95% CI, 1.06–1.37; and adjusted hazard ratio, 1.29; 95% CI, 1.11–1.51, respectively). Among those with MDD, baseline antidepressant use was associated with lower risk of incident HF events (adjusted hazard ratio, 0.76; 95% CI, 0.58–0.99). Conclusions— Our study is the first to suggest that MDD is an independent risk factor for HF in HIV+ adults. These results reinforce the importance of identifying and managing MDD among HIV+ patients. Future studies must clarify mechanisms linking HIV, MDD, antidepressants, and HF and identify interventions to reduce HF morbidity and mortality in those with both HIV and MDD.
Transmission of rheumatoid arthritis through blood transfusion: a retrospective cohort study
Authors: Søren Andreas Just, Klaus Rostgaard, Kjell Titlestad ‎, Gustaf Edgren, Christian Erikstrup, Henrik Ullum, Ole Birger Pedersen, Kaspar Rene Nielsen, Johan Askling, Hanne Lindegaard, Henrik Hjalgrim
Journal: Annals of the Rheumatic Diseases (2018)

The long preclinical phase of rheumatoid arthritis (RA), where some factors involved in RA pathogenesis circulate peripherally, raises concern of RA transmissibility through blood transfusion.1 Specifically, this possibility is suggested by murine RA models in which anticitrullinated peptide/protein antibodies may induce and enhance arthritis, and precursors of the RA-fibroblast-like synoviocyte cells may aggravate and spread the disease between joints.2 3 

We used a large Danish–Swedish population-based research donations and transfusions database (SCANDAT2) with health register information on 1.5 million blood donors and 2.1 million recipients of their blood to investigate (1) RA occurrence in recipients of blood from donors who later developed RA and (2) clustering of RA among recipients of blood from individual donors, regardless of the donor’s RA status.4–6 

We used two different approaches to analyse RA transmission. First, we identified all donors who developed RA after blood donation. For each of these index donors, we identified up to 10 donors matched on age, sex, county, date of first donation, number of donations and ABO blood group, who were free of RA at the date …
Most GPs say general practice is more stressful than five years ago
Authors: Helen Jaques
Journal: BMJ (2013)

Most GPs (93%) think that working in general practice is more stressful than it was five years ago, shows a poll conducted by the Royal College of General Practitioners. 

The snapshot survey of 258 of the college’s 44 000 members across the UK found that most respondents (84%) believed that their workload had increased substantially over the past five years. …
Get Through The Foundation Years: A Handbook for Junior Doctors
Authors: Shahida Parveen Azeez
Journal: BMJ (2005)

Ed Ashis Banerjee

RSM Press, 2005, £14.95, 125 pages

ISBN 1 85315 691 4

Rating: ⋆⋆⋆/5



August 2005 saw the launch of the foundation programme for new doctors—a first step outside medical school for the newly qualified. With dust settling in from pilot runs of the foundation programme, and PMETB (the Postgraduate Medical Education and Training Board) assuming new responsibilities, the offspring foundation programme of Modernising Medical Careers is rapidly shaping into a little giant.

Searching the internet might be a reasonable option for junior doctors wanting to gather information on the foundation programme, provided they know …
Diploma in medical jurisprudence (DMJ (Clin))
Authors: Hadrian Ball
Journal: BMJ (2005)

There are three versions of the DMJ. The clinical version is usually sought by doctors practising as forensic medical examiners (formerly known as police surgeons); the pathology version is for pathologists specialising in the field of forensic pathology; and the odontology version is for aspiring forensic odontologists.

I sat this diploma relatively late in my career. I was appointed as a consultant forensic psychiatrist in July 1992. I sat the first part of the diploma in October 2003 and the …
A guide to clinical attachments
Authors: Lynette T Hlatywayo
Journal: BMJ (2005)

General Medical Council (GMC) figures show that there are about 210 000 registered doctors in the United Kingdom, of whom 80 000 are in hospital practice. Each year 13 000 doctors register for the first time with the GMC. Of these, 40% are from UK medical schools, 15% are EEA (European Economic Area) nationals with EEA qualifications, and 45% are non-EEA doctors or overseas doctors—now called international medical graduates (IMGs; J Mullin, personal communication, 2004).

IMGs come to the United Kingdom for further training and specialisation, and eventually about 25-30% join the medical workforce permanently, either as GPs, specialists, or consultants.

Some royal colleges, such as the Royal College of Obstetricians and Gynaecologists, have schemes such as the Overseas Doctors Training Fellowship scheme (ODTF) and the Double Ended Sponsorship Scheme (DESS), which accept around 200 IMGs each year for postgraduate training and return to their native country.

The vast majority of IMGs come to the United Kingdom without any sponsorship or scholarship. This may be in response to reports of a shortage of doctors here, but the paradox is that the United Kingdom is short of consultants and GPs, not junior doctors. The average number of applicants for a new F2 foundation post is 400 and for a standard senior house officer post is 200.1

Only accredited specialists from the EEA can become UK GPs and consultants without further training.

A clinical attachment is one of the best ways an IMG can learn about the NHS and UK clinical practice. It boosts confidence and enhances the chances of passing exams, …
Effects of continuous positive airway pressure therapy on left ventricular diastolic function: a randomised, sham-controlled clinical trial
Authors: Chi Young Shim, Darae Kim, Sungha Park, Chan Joo Lee, Hyung-Ju Cho, Jong-Won Ha, Yang-Je Cho, Geu-Ru Hong
Journal: European Respiratory Journal (2018)

Continuous positive airway pressure (CPAP) therapy may decrease left ventricular (LV) loads and improve myocardial oxygenation. In this study, we investigated the effect of CPAP on LV diastolic function compared with sham treatment in patients with severe obstructive sleep apnoea (OSA). This 3-month prospective single-centre randomised sham-controlled trial analysed 52 patients with severe OSA. Patients were randomly assigned (1:1) to receive either CPAP or sham treatment for 3 months. The main investigator and patients were masked to the trial randomisation. The primary end-point was change of early diastolic mitral annular (e′) velocity over the 3-month period. Secondary end-points were pulse wave velocity (PWV), 24-h ambulatory blood pressure (BP) and variables of ventricular-vascular coupling at 3 months. After 3 months of follow-up, CPAP treatment significantly increased the e′ velocity, and was greater than the sham treatment (0.65±1.70 versus −0.61±1.85 cm·s −1 , p=0.014). The PWV, 24-h mean diastolic BP, night-time diastolic BP, arterial elastance index and ventricular-vascular coupling index after 3 months of follow-up decreased significantly in the CPAP group. In patients with severe OSA, CPAP treatment for 3 months improved LV diastolic function more than sham treatment, and was accompanied by improvements in arterial stiffness and ventricular-vascular coupling.
Working beyond age 60 doesn’t affect performance, review finds
Authors: Helen Jaques
Journal: BMJ (2013)

Most workers in their 60s show only “slight” decreases in their capacity and performance, an audit of existing research on the effects of working beyond the age of 60 has found.

From 2015 the normal retirement age for NHS pension scheme members will rise to the state pension age—currently 65 for men and 60 for women—but will rise to 68 by 2046. At present the normal retirement age for members of the NHS pension scheme is 60 for those in the 1995 version or 65 for the 2008 version.

A research audit was commissioned as part of the Impact of …
What happens to couples—will they be able to stay together?
Authors: Sarah Thomas
Journal: BMJ (2006)

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