tbuckley/cabot-search huggingface dataset:
Feasibility and clinical utility of EUS guided biopsy of pancreatic cancer for next-generation genomic sequencing.
Authors: Stephan Dreyer, Nigel Jamieson, Lisa Evers, Marc Jones, Sancha Martin, Fraser Duthie, Liz Musgrove, Susie Cooke, Peter Bailey, Colin McKay, David Kuang-Fu Chang, Andrew Biankin
Journal: Journal of Clinical Oncology (2018)

296 Background: Next-generation sequencing technology has made genomic profiling guided therapy a reality for many cancer types. The aim of this study is to investigate the feasibility of genomic profiling using standard clinical endoscopic ultrasound (EUS) core biopsy samples of Pancreatic Cancer (PC) to allow personalised cancer care. Methods: 78 patients underwent additional research biopsy at the time of diagnostic EUS biopsy. En-face frozen section was performed to enable targeted macro-dissection prior to DNA extraction, quantification and targeted gene sequencing (Agilent Comprehensive Cancer Gene Panel). Matching formalin-fixed (FFPE) diagnostic EUS biopsies and fresh frozen surgical resection specimens also underwent genomic profiling for comparison. Whole genome (WGS) and RNA sequencing was performed in selected patients. Results: Targeted panel sequencing ( n = 61) revealed known PC genes ( KRAS, GNAS, TP53, CDKN2A, SMAD4) in 36 patients with histological evidence of PC. Potentially actionable somatic mutations (BRCA1, BRCA2, ATM, BRAF, JAK3) were found in 6 (17%) patients. WGS ( n = 5) of EUS samples confirmed mutations identified on panel sequencing and revealed relevant mutational signatures and structural variation patterns that can act as putative biomarkers of therapeutic responsiveness. RNA sequencing ( n = 54) segregated patients into key clinically relevant molecular PC subtypes based on transcriptome and reveals novel molecular insights into advanced, unresectable PC ( n = 38). Conclusions: We demonstrate here novel multi-omic analysis of pancreatic cancer using standard clinical EUS guided fine needle biopsies. Multi-omic analysis of EUS biopsies offers potential clinical utility to guide personalized therapy of PC in both the neoadjuvant and advanced settings.
Essential Facts In Geriatric Medicine
Authors: Yogesh Ganeshalingam
Journal: BMJ (2005)

Catherine Bracewell, Rosaire Gray, and Gurcharan S Rai

Radcliffe Publishing, 2005, £19.95 pb, 213 pages ISBN: 1 85775 867 6

Rating: ⋆⋆⋆⋆/5



As a psychiatry senior house officer (SHO) approaching my next SHO post in old age psychiatry I felt that as my psychiatric knowledge had grown, my medical skills had declined through a lack of exposure and a priority now aimed at the MRCPsych curriculum. I was about to enter a psychiatry specialty, where a sound understanding of organic illnesses is desirable, when I came across Essential Facts in Geriatric Medicine .

Written …
Letter by Jin-shan and Xue-bin Regarding Article, “Lower Risk of Heart Failure and Death in Patients Initiated on Sodium-Glucose Cotransporter-2 Inhibitors Versus Other Glucose-Lowering Drugs: The CVD-REAL Study (Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors)”
Authors: He Jin-shan, Li Xue-bin
Journal: Circulation (2018)
Cholangiocyte‐derived exosomal long noncoding RNA H19 promotes cholestatic liver injury in mouse and humans
Authors: Xiaojiaoyang Li, Runping Liu, Zhiming Huang, Emily C. Gurley, Xuan Wang, Juan Wang, Hongliang He, Hu Yang, Guanhua Lai, Luyong Zhang, Jasmohan S. Bajaj, Melanie White, William M. Pandak, Phillip B. Hylemon, Huiping Zhou
Journal: Hepatology (2018)

Cholestatic liver injury is an important clinical problem with limited understanding of disease pathologies. Exosomes are small extracellular vesicles released by a variety of cells, including cholangiocytes. Exosome‐mediated cell‐cell communication can modulate various cellular functions by transferring a variety of intracellular components to target cells. Our recent studies indicate that the long noncoding RNA (lncRNA), H19, is mainly expressed in cholangiocytes, and its aberrant expression is associated with significant down‐regulation of small heterodimer partner (SHP) in hepatocytes and cholestatic liver injury in multidrug resistance 2 knockout (Mdr2 −/− ) mice. However, how cholangiocyte‐derived H19 suppresses SHP in hepatocytes remains unknown. Here, we report that cholangiocyte‐derived exosomes mediate transfer of H19 into hepatocytes and promote cholestatic injury. Hepatic H19 level is correlated with severity of cholestatic injury in both fibrotic mouse models, including Mdr2 −/− mice, a well‐characterized model of primary sclerosing cholangitis (PSC), or CCl 4 ‐induced cholestatic liver injury mouse models, and human PSC patients. Moreover, serum exosomal‐H19 level is gradually up‐regulated during disease progression in Mdr2 −/− mice and patients with cirrhosis. H19‐carrying exosomes from the primary cholangiocytes of wild‐type (WT) mice suppress SHP expression in hepatocytes, but not the exosomes from the cholangiocytes of H19 −/− mice. Furthermore, overexpression of H19 significantly suppressed SHP expression at both transcriptional and posttranscriptional levels. Importantly, transplant of H19‐carrying serum exosomes of old fibrotic Mdr2 −/− mice significantly promoted liver fibrosis (LF) in young Mdr2 −/− mice. Conclusion: Cholangiocyte‐derived exosomal‐H19 plays a critical role in cholestatic liver injury. Serum exosomal H19 represents a noninvasive biomarker and potential therapeutic target for cholestatic diseases. (H epatology 2018).
Characteristics of and Precipitating Circumstances Surrounding Suicide Among Persons Aged 10–17 Years — Utah, 2011–2015
Authors: Francis B. Annor, Marissa L. Zwald, Amanda Wilkinson, Mike Friedrichs, Anna Fondario, Angela Dunn, Allyn Nakashima, Leah K. Gilbert, Asha Z. Ivey-Stephenson
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

In 2015, suicide was the third leading cause of death among persons aged 10-17 years (1), and in Utah, the age-adjusted suicide rate was consistently higher than the national rate during the past decade (2). In January 2017, the Utah Department of Health (UDOH) invited CDC to assist with an epidemiologic investigation of suicides among youths aged 10-17 years during 2011-2015 to identify precipitating factors. CDC analyzed data from the Utah Violent Death Reporting System (UTVDRS), National Vital Statistics System, and additional information collected in the field. During 2011-2015 in Utah, 150 youths died by suicide. Approximately three fourths of decedents were male (77.4%) and aged 15-17 years (75.4%). During this period, the unadjusted suicide rate per 100,000 youths in Utah increased 136.2%, from 4.7 per 100,000 population (2011) to 11.1 (2015), whereas among youths nationwide, the rate increased 23.5%, from 3.4 to 4.1. Among suicide decedents with circumstances data available, more than two thirds (68.3%) had multiple precipitating circumstances, including mental health diagnosis (35.2%), depressed mood (31.0%), recent crisis (55.3%), and history of suicidal ideation or attempt (29.6%). CDC's technical package of policies, programs, and practices to prevent suicide supported by the best available evidence can be used as a suicide prevention resource (3).
Subspecialisation is threatened by Shape of Training review, BMA warns
Authors: Kathy Oxtoby
Journal: BMJ (2015)

Subspecialisation is under threat if the recommendations of a major review of postgraduate medical education and training are implemented, the BMA has warned.

The UK-wide Shape of Training review, carried out by David Greenaway, vice chancellor of Nottingham University, recommends that most clinicians should have a generalist qualification and says that employers should be responsible for subspecialty training.1

However, …
Correlation of primary biopsy mutational landscape to pre-docetaxel LDH for prediction of docetaxel therapeutic response.
Authors: Kenneth Hiew, Claire Alexandre Hart, Adnan Ali, Maurice Lau, Vijay A.C. Ramani, Vijay Sangar, Satish Maddineni, Tony Elliott, Noel Clarke, Mick D. Brown
Journal: Journal of Clinical Oncology (2018)

220 Background: There is a lack of biomarkers to predict docetaxel response. Here we assess the potential of pre-treatment LDH, associated to the mutational background of the primary biopsy taken prior to 1 st line therapy with ADT, to predict docetaxel response in the castrate resistant setting. Methods: Clinical and associated primary biopsy targeted next-generation sequencing data from matched training (n = 150) and test (n = 120) sets of retrospective progressive mCRPC patients (diagnosed 1996-2006) treated with docetaxel therapy were analyzed. LDH thresholds were determined and validated on the training and test sets respectively. Clinico-pathological associations with LDH were assessed using student t-test, Wilcoxon test and Chi-square test and predictive value of LDH determined by linear regression analysis for PSA and radiologic response. Time to event outcomes (PFS &amp; OS) was evaluated by Kaplan-Meier. Meta-analysis of LDH association with DNA repair genes in the MSKCC and SU2C/PCF was conducted using cBioPortal Results: Using pre-docetaxel serum LDH of ≥450U/L as a prognostic threshold (AUC:0.75 (SD 0.054, 95% CI, 0.650–0.864, P &lt; 0.001)) patients with LDH ≥450U/L were poorer PSA responders, with shorter PFS (213 vs 372 days, HR 1.876 (95% CI, 1.289-2.730)) and OS (362 vs 563 days, HR 1.630 (95% CI, 1.127-2.357)). LDH was also an independent surrogate marker for prediction of poor radiologic response and survival following docetaxel chemotherapy (P = 0.043). Genomic analysis showed that patients with LDH ≥450U/L (9/14 (64.3%)) have a higher tumour mutational burden (TMB) at the point of primary pre-ADT biopsy (mean, 46.2 vs 6.2 mutations/MB; p = 0.129) and that they were more likely to have DNA repair gene mutation(s) (BRCA1/2, ATM, CHEK2 and Fanconi’s anemia gene). Meta-analysis of the large MSKCC and the SU2C-PCF patient genomic databases confirmed the positive correlation between the LDH gene LDHA and PARP1 gene (r = 0.667, p &lt; 0.01) expression and expression of other DNA repair genes. Conclusions: High pre-treatment serum LDH coupled with mutations in the DNA repair pathway in primary pre-ADT biopsy correlates with poor docetaxel response and overall survival in the castrate resistant state.
Dermoscopy and Overdiagnosis of Melanoma In Situ
Authors: Kaitlin L. Nufer, Anthony P. Raphael, H. Peter Soyer
Journal: JAMA Dermatology (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Genome-Wide Association Study in African Americans with Acute Respiratory Distress Syndrome Identifies the Selectin P Ligand Gene as a Risk Factor
Authors: Christian Bime, Nima Pouladi, Saad Sammani, Ken Batai, Nancy Casanova, Tong Zhou, Carrie L. Kempf, Xiaoguang Sun, Sara M. Camp, Ting Wang, Rick A. Kittles, Yves A. Lussier, Tiffanie K. Jones, John P. Reilly, Nuala J. Meyer, Jason D. Christie, Jason H. Karnes, Manuel Gonzalez-Garay, David C. Christiani, Charles R. Yates, Mark M. Wurfel, Gianfranco U. Meduri, Joe G. N. Garcia
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Genetic factors are involved in acute respiratory distress syndrome (ARDS) susceptibility. Identification of novel candidate genes associated with increased risk and severity will improve our understanding of ARDS pathophysiology and enhance efforts to develop novel preventive and therapeutic approaches.
Can you suggest the best way of getting medical indemnity insurance for general practitioner vocational training schemes at a good price?
Authors: Matthew Lee
Journal: BMJ (2004)

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 (www.bmjcareers.com/advicezone) 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.
Cost-effectiveness of <i>KRAS</i>, <i>EGFR</i> and <i>ALK</i> testing for decision making in advanced nonsmall cell lung carcinoma: the French IFCT-PREDICT.amm study
Authors: Sandrine Loubière, Alexandre Drezet, Michèle Beau-Faller, Denis Moro-Sibilot, Sylvie Friard, Marie Wislez, Hélène Blons, Catherine Daniel, Virginie Westeel, Anne Madroszyk, Hervé Léna, Patrick Merle, Julien Mazières, Gérard Zalcman, Roger Lacave, Martine Antoine, Franck Morin, Pascale Missy, Fabrice Barlesi, Pascal Auquier, Jacques Cadranel
Journal: European Respiratory Journal (2018)

ALK rearrangement and EGFR / KRAS mutations constitute the primary biomarkers tested to provide targeted or nontargeted therapies in advanced nonsmall cell lung cancer (NSCLC) patients. Our objective was to assess the cost-effectiveness of biomarker testing for NSCLC. Between 2013 and 2014, 843 treatment-naive patients were prospectively recruited at 19 French hospitals into a longitudinal observational cohort study. Two testing strategies were compared, i.e. with “at least one biomarker status known” and “at least KRAS status known”, in addition to “no biomarker testing” as the reference strategy. The Kaplan–Meier approach was employed to assess restricted mean survival time. Direct medical costs incurred by hospitals were estimated with regard to treatment, inpatient care and biomarker testing. Compared with “no biomarker testing”, the “at least one biomarker status known” strategy yielded an incremental cost-effectiveness ratio of EUR13 230 per life-year saved, which decreased to EUR7444 per life-year saved with the “at least KRAS status known” testing strategy. In sensitivity analyses, biomarker testing strategies were less costly and more effective in 41% of iterations. In summary, molecular testing prior to treatment initiation proves to be cost-effective in advanced NSCLC management and may assist decision makers in defining conditions for further implementation of these innovations in general practice.
IMPACT OF BODY MASS INDEX AND OBESITY ON CLINICAL OUTCOMES IN THE EDOXABAN VERSUS WARFARIN IN SUBJECTS UNDERGOING CARDIOVERSION OF ATRIAL FIBRILLATION (ENSURE-AF) RANDOMIZED TRIAL
Authors: Greg Lip, Jose L. Merino, Maciej Banach, Joris de Groot, Lars Maier, Sakis Themistoclakis, James Jin, Michael Melino, Shannon Winters, Andreas Goette
Journal: Journal of the American College of Cardiology (2018)
SPECTRUM OF CORONARY ARTERY CALCIUM (CAC) ACCORDING TO AGE, GENDER, RACE IN A MULTI-ETHNIC ASIAN POPULATION
Authors: Shu Yun Heng, Jien Sze Ho, Foong Koon Cheah, Terrance Chua Siang Jin, Felix Keng Yung Jih, Lohendran Baskaran, Seyed Ehsan Saffari, Swee Yaw Tan
Journal: Journal of the American College of Cardiology (2018)
There seems to be a shortage of GP equity partnerships being advertised, especially in the south west. Why do you think this is?
Authors: Bill Irish
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 (www.bmjcareers.com/advicezone) 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.
Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women
Authors: Lesley Hoyles, José-Manuel Fernández-Real, Massimo Federici, Matteo Serino, James Abbott, Julie Charpentier, Christophe Heymes, Jèssica Latorre Luque, Elodie Anthony, Richard H. Barton, Julien Chilloux, Antonis Myridakis, Laura Martinez-Gili, José Maria Moreno-Navarrete, Fadila Benhamed, Vincent Azalbert, Vincent Blasco-Baque, Josep Puig, Gemma Xifra, Wifredo Ricart, Christopher Tomlinson, Mark Woodbridge, Marina Cardellini, Francesca Davato, Iris Cardolini, Ottavia Porzio, Paolo Gentileschi, Frédéric Lopez, Fabienne Foufelle, Sarah A. Butcher, Elaine Holmes, Jeremy K. Nicholson, Catherine Postic, Rémy Burcelin, Marc-Emmanuel Dumas
Journal: Nature Medicine (2018)
I have just passed the PLAB and wish to have a career in anaesthetics and critical care medicine. I have worked in anaesthetics for six months in India. Which jobs should I apply for to get on to an anaesthetic rotation? Should I apply for the non-training jobs in accident and emergency?
Authors: Peter Shirley
Journal: BMJ (2004)

<i>Got 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 (www.bmjcareers.com/advicezone) 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.</i>
Excitation‐Dependent Theranostic Nanosheet for Cancer Treatment
Authors: Shanyue Guan, Di Yang, Yangziwan Weng, Heng Lu, Xiangmin Meng, Xiaozhong Qu, Shuyun Zhou
Journal: Advanced Healthcare Materials (2018)

In this work, a novel ruthenium complex loaded monolayer layered double hydroxide (LDH) (denoted as Ru(C-bpy)2 /mLDH) as supramolecular nanosensor is synthesized, which is greatly exclusive to the hypoxic tumor microenvironment. The Ru(C-bpy)2 /mLDH ultrathin sheet displays not only enhanced luminescence lifetime compared to the parent Ru(C-bpy)2 alone, but also improved oxygen responsibility under an excitation of 488 or 800 nm. Moreover, the Ru(C-bpy)2 /mLDH is possessed of two-photon fluorescence imaging ability under the 800 nm irradiation. In addition, the Ru(C-bpy)2 /mLDH can generate singlet oxygen with a high yield (φ∆ ) of 0.28 under the 520 nm irradiation, while the φ∆ of Ru(C-bpy)2 is 0.19. Therefore, the Ru(C-bpy)2 /mLDH can be applied as a supramolecular theranostic agent with light-switchable cancer imaging and photodynamic therapy properties.
Doctors in Scotland fear that independence would affect recruitment
Authors: Abi Rimmer
Journal: BMJ (2014)

Doctors in Scotland are concerned that an independent Scotland would struggle to recruit medical staff, comments submitted in response to a survey by The BMJ have shown.

Ahead of September’s referendum, a survey of 311 doctors in Scotland by The BMJ found that 60% planned to vote “no” to independence, while just a third (33%) intended to vote “yes.” A further 6% were undecided, and 1% said that they did not plan to vote.1

Commenting in response to The BMJ ’s survey, …
Surface Enhanced Raman Spectroscopy (SERS) for the Multiplex Detection of Braf, Kras, and Pik3ca Mutations in Plasma of Colorectal Cancer Patients
Authors: Xiaozhou Li, Tianyue Yang, Caesar Siqi Li, Youtao Song, Hong Lou, Dagang Guan, Lili Jin
Journal: Theranostics (2018)

In this paper, we discuss the use of a procedure based on polymerase chain reaction (PCR) and surface enhanced Raman spectroscopy (SERS) (PCR-SERS) to detect DNA mutations.Methods: This method was implemented by first amplifying DNA-containing target mutations, then by annealing probes, and finally by applying SERS detection.The obtained SERS spectra were from a mixture of fluorescence tags labeled to complementary sequences on the mutant DNA.Then, the SERS spectra of multiple tags were decomposed to component tag spectra by multiple linear regression (MLR).Results: The detection limit was 10 -11 M with a coefficient of determination (R 2 ) of 0.88.To demonstrate the applicability of this process on real samples, the PCR-SERS method was applied on blood plasma taken from 49 colorectal cancer patients to detect six mutations located at the BRAF, KRAS, and PIK3CA genes.The mutation rates obtained by the PCR-SERS method were in concordance with previous research.Fisher's exact test showed that only two detected mutations at BRAF (V600E) and PIK3CA (E542K) were significantly positively correlated with right-sided colon cancer.No other clinical feature such as gender, age, cancer stage, or differentiation was correlated with mutation (V600E at BRAF, G12C, G12D, G12V, G13D at KRAS, and E542K at PIK3CA).Visually, a dendrogram drawn through hierarchical clustering analysis (HCA) supported the results of Fisher's exact test.The clusters drawn by all six mutations did not conform to the distributions of cancer stages, differentiation or cancer positions.However, the cluster drawn by the two mutations of V600E and E542K showed that all samples with those mutations belonged to the right-sided colon cancer group. Conclusion:The suggested PCR-SERS method is multiplexed, flexible in probe design, easy to incorporate into existing PCR conditions, and was sensitive enough to detect mutations in blood plasma.
Within-Day, Between-Day, and Between-Week Variability of Urinary Concentrations of Phenol Biomarkers in Pregnant Women
Authors: Céline Vernet, Claire Philippat, Antonia M. Calafat, Xiaoyun Ye, Sarah Lyon-Caen, Valérie Siroux, Enrique F. Schisterman, Rémy Slama
Journal: Environmental Health Perspectives (2018)

Background: Toxicology studies have shown adverse effects of developmental exposure to industrial phenols. Evaluation in humans is challenged by potentially marked within-subject variability of phenol biomarkers in pregnant women, which is poorly characterized. Objectives: We aimed to characterize within-day, between-day, and between-week variability of phenol urinary biomarker concentrations during pregnancy. Methods: In eight French pregnant women, we collected all urine voids over a 1-wk period (average, 60 samples per week per woman) at three occasions (15±2, 24±2, and 32±1 gestational weeks) in 2012–2013. Aliquots of each day and of the whole week were pooled within-subject. We assayed concentrations of 10 phenols in these pools, and, for two women, in all spot (unpooled) samples collected during a 1-wk period. We characterized variability using intraclass correlation coefficients (ICCs) with spot samples (within-day variability), daily pools (between-day variability), and weekly pools (between-week variability). Results: For most biomarkers, the within-day variability was high (ICCs between 0.03 and 0.50). The between-day variability, based on samples pooled within each day, was much lower, with ICCs &gt;0.60 except for bisphenol S (0.14, 95% confidence interval [CI]: 0.00, 0.39). The between-week variability differed between compounds, with triclosan and bisphenol S having the lowest ICCs (&lt;0.3) and 2,5-dichlorophenol the highest (ICC &gt;0.9). Conclusion: During pregnancy, phenol biomarkers showed a strong within-day variability, while the variability between days of a given week was more limited. One biospecimen is not enough to efficiently characterize exposure; collecting biospecimens during a single week may be enough to represent well the whole pregnancy exposure for some but not all phenols. https://doi.org/10.1289/EHP1994