tbuckley/cabot-search huggingface dataset:
The Immunome of Colon Cancer: Functional In Silico Analysis of Antigenic Proteins Deduced from IgG Microarray Profiling
Authors: Johana A. Luna Coronell, Khulan Sergelen, Philipp Hofer, István Gyurján, Stefanie Brezina, Peter Hettegger, Gernot Leeb, Karl Mach, Andrea Gsur, Andreas Weinhäusel
Journal: Genomics Proteomics & Bioinformatics (2018)

Abstract Characterization of the colon cancer immunome and its autoantibody signature from differentially-reactive antigens (DIRAGs) could provide insights into aberrant cellular mechanisms or enriched networks associated with diseases. The purpose of this study was to characterize the antibody profile of plasma samples from 32 colorectal cancer (CRC) patients and 32 controls using proteins isolated from 15,417 human cDNA expression clones on microarrays. 671 unique DIRAGs were identified and 632 were more highly reactive in CRC samples. Bioinformatics analyses reveal that compared to control samples, the immunoproteomic IgG profiling of CRC samples is mainly associated with cell death, survival, and proliferation pathways, especially proteins involved in EIF2 and mTOR signaling. Ribosomal proteins (e.g., RPL7, RPL22, and RPL27A) and CRC-related genes such as APC, AXIN1, E2F4, MSH2, PMS2, and TP53 were highly enriched. In addition, differential pathways were observed between the CRC and control samples. Furthermore, 103 DIRAGs were reported in the SEREX antigen database, demonstrating our ability to identify known and new reactive antigens. We also found an overlap of 7 antigens with 48 “CRC genes.” These data indicate that immunomics profiling on protein microarrays is able to reveal the complexity of immune responses in cancerous diseases and faithfully reflects the underlying pathology.
Thousands of jobs could be lost unless region switches to local terms and conditions, warns South West “pay cartel”
Authors: Caroline White
Journal: BMJ (2012)

Up to 6000 NHS jobs across the South West of England could be axed unless steps are taken to change the pay and conditions of all staff, including doctors, in the region, suggests a consortium of 20 NHS trusts.

In a brace of discussion documents that consider how pay and conditions could be used to help trusts meet “the serious financial and operating challenges facing the NHS,” the South West Pay Terms and Conditions Consortium (SWC) claims there are no other options left if jobs are to be safeguarded.

“The alternative to addressing pay, terms, and conditions is a wholesale reduction in headcount, which, in potentially compromising minimum staffing levels and therefore patient safety, is extremely undesirable and costly,” it …
Lung Recruitment and Positive End-Expiratory Pressure Titration in Patients With Acute Respiratory Distress Syndrome
Authors: Andrew C. McKown, Matthew W. Semler, Todd W. Rice
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
THE COMPLEMENTARY VALUE OF THE GET WITH THE GUIDELINES: HEART FAILURE RISK SCORE AND LABORATORY MARKERS AT DISCHARGE IN PREDICTING MORTALITY IN PATIENTS HOSPITALIZED WITH HEART FAILURE WITH PRESERVED EJECTION FRACTION
Authors: Kalyani Boralkar, Yukari Kobayashi, Vedant Pargaonkar, Kegan Moneghetti, Mirela Tuzovic, Gomathi Krishnan, Myriam Amsallem, Tatiana Kouznetsova, Benjamin Horne, Kirk Knowlton, Paul Heidenreich, Francois Haddad
Journal: Journal of the American College of Cardiology (2018)
How the General Medical Council’s national training survey helps improve medical education
Authors: Peter Rubin, Sonia Panchal
Journal: BMJ (2014)

Each year, the General Medical Council conducts its national training survey to monitor the quality of medical education and training, and the 2014 survey is now open. <b>Peter Rubin</b>, the council’s chairman, and <b>Sonia Panchal</b>, a specialist trainee, discuss how the survey is used to improve training, and the importance of using it to provide open and honest feedback
Iron deficiency impairs contractility of human cardiomyocytes through decreased mitochondrial function
Authors: Martijn F. Hoes, Niels Grote Beverborg, J. David Kijlstra, Jeroen Kuipers, Dorine W. Swinkels, Ben N.G. Giepmans, Richard J. Rodenburg, Dirk J. van Veldhuisen, Rudolf A. de Boer, Peter van der Meer
Journal: European Journal of Heart Failure (2018)

Aims Iron deficiency is common in patients with heart failure and associated with a poor cardiac function and higher mortality. How iron deficiency impairs cardiac function on a cellular level in the human setting is unknown. This study aims to determine the direct effects of iron deficiency and iron repletion on human cardiomyocytes. Methods and results Human embryonic stem cell‐derived cardiomyocytes were depleted of iron by incubation with the iron chelator deferoxamine (DFO). Mitochondrial respiration was determined by Seahorse Mito Stress test, and contractility was directly quantified using video analyses according to the BASiC method. The activity of the mitochondrial respiratory chain complexes was examined using spectrophotometric enzyme assays. Four days of iron depletion resulted in an 84% decrease in ferritin ( P &lt; 0.0001) and significantly increased gene expression of transferrin receptor 1 and divalent metal transporter 1 (both P &lt; 0.001). Mitochondrial function was reduced in iron‐deficient cardiomyocytes, in particular ATP‐linked respiration and respiratory reserve were impaired (both P &lt; 0.0001). Iron depletion affected mitochondrial function through reduced activity of the iron–sulfur cluster containing complexes I, II and III, but not complexes IV and V. Iron deficiency reduced cellular ATP levels by 74% ( P &lt; 0.0001) and reduced contractile force by 43% ( P &lt; 0.05). The maximum velocities during both systole and diastole were reduced by 64% and 85%, respectively (both P &lt; 0.001). Supplementation of transferrin‐bound iron recovered functional and morphological abnormalities within 3 days. Conclusion Iron deficiency directly affects human cardiomyocyte function, impairing mitochondrial respiration, and reducing contractility and relaxation. Restoration of intracellular iron levels can reverse these effects.
O010 Increased GPR22 activation triggers osteoarthritis
Authors: L-A Guns, S Monteagudo, D Calebiro, M Lohse, F Cailotto, R Lories
Journal: Annals of the Rheumatic Diseases (2018)

Introduction  G protein-coupled receptors (GPCRs) are considered interesting drug targets. GPR22, an orphan receptor, was previously associated to osteoarthritis (OA) in a genome wide association study.  Objectives  To investigate GPR22 expression in human healthy and OA cartilage and asses the functional role of GPR22 with in vitro and in vivo models.  Methods  GPR22 protein levels were examined by immunohistochemistry. Chondrogenic ATDC5 cells stably overexpressing Gpr22 (GPR22+) and embryonic limb bud cells from mutant Gpr22V385A/V385A mice were cultured as micromasses, and read-outs included gene expression and evaluation of the extracellular matrix. Downstream GPR22 signalling was determined with a PKA activity fluorescence-based assay. Cholecystokinin receptor antagonist AG-041R was tested as GPR22 antagonist. PKA concentrations and kinetics were measured by fluorescence resonance energy transfer (FRET) imaging by PKA sensors in ATDC5 cells. Destabilisation or removal of the medial meniscus (DMM or TMM), for 12 or 8 weeks respectively, was surgically induced in mutant 8 week-old Gpr22V385A/V385A and wild-type C57/Bl6 mice. Vehicle or AG-041R was injected in the knee joint every 5 days, starting 1 week post-DMM until the mice were sacrificed. Severity was analysed according to OARSI scoring and immunohistochemistry.  Results  In healthy human articular cartilage, GPR22 protein was absent, while it is present in OA cartilage. GPR22 +cells showed increased mineralization and decreased proteoglycan content compared to controls after 21 days. Gene expression demonstrated a decrease in Aggrecan and Collagen 2. In contrast, levels of hypertrophic markers Col10 and Mmp13 were increased, suggesting a shift of the cells’ differentiation status. PKA activity was reduced in GPR22 +cells compared to controls. The effects on markers, proteoglycan content and mineralization were antagonised by AG-041R. FRET imaging confirmed the neutralising effect of AG-041R on intracellular PKA concentration in GPR22 +cells. In vivo, DMM- and TMM- operated knees of GPR22 V385A/V385A mice showed increased cartilage damage, and increased GPR22 and COL10 expression compared to controls. Intra-articular injections of AG-041R prevented cartilage damage in DMM-induced GPR22 V385A/V385A mice.  Conclusions  GPR22 is present in human OA cartilage and not in healthy tissue. Overexpression of GPR22 accelerates chondrocyte hypertrophy. GPR22 can be antagonised by AG-041R. Our preliminary in vivo data show a therapeutic effect of AG-041R in the DMM model. Thus, GPR22 is genetically and functionally linked to OA and may be a potential therapeutic target.  Disclosure of interest  None declared
What are the chances of a non-European Union resident getting a type 1 training number in orthopaedics? Is there any chance that I could be a consultant in orthopaedics in the United Kingdom? (I am a Pakistani national.)
Authors: Andy Goldberg
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>
The combination of platelet count and neutrophil to lymphocyte ratio (COP-NLR) for prediction of treatment outcome for patients with localized renal cell carcinoma.
Authors: Kazumasa Komura, Takuya Tsujino, Naokazu Ibuki, Teruo Inamoto, Haruhito Azuma
Journal: Journal of Clinical Oncology (2018)

598 Background: The combination of platelet count and neutrophil to lymphocyte ratio (COP-NLR) has been shown to provide prognostic information in several cancers. The object of the present study was to examine the preoperative prognostic value of the COP-NLR in localized RCC. Methods: The records of 268 patients were analyzed in the study. The cut-off value of platelet count and NLR were defined by receive operating characteristic (ROC) analysis and the areas under the curve (AUC). Patients with both an increased platelet count ( &gt; 31.0×10 4 mm -3 ) and an elevated NLR ( &gt; 3.85) were assigned a score of 2, and patients with one or neither were assigned as a score of 1 or 0, respectively. Results: There were 198, 63, and 7 patients assigned to the COP-NLR of 0, 1, and 2, respectively. Five year OS rates were 93.8% in COP-NLR0, 72.2% in COP-NLR1 and 0% in COP-NLR 2, demonstrating a significant difference in their prognosis among the COP-NLR in localized RCC patients. Multivariate analysis using the 10 clinicopathological findings selected by univariate analyses demonstrated that the preoperative COP-NLR was an independent prognostic factor for OS (HR: 2.32, 95%CI: 1.22 to 4.26, p = 0.011) and RFS (HR: 1.91, 95%CI: 1.02 to 3.53, p = 0.044). Conclusions: The preoperative COP-NLR is an independent prognostic indicator of OS and RFS for patients with localized RCC. [Table: see text]
Situational judgment test and decile based performance measure are to be used for entry to foundation programme
Authors: Helen Jaques
Journal: BMJ (2012)

From 2013 all applicants to the foundation programme will have to take a situational judgment test (SJT) and will be ranked on a new educational performance measure (EPM), in addition to completing their foundation programme application, the Department of Health has confirmed.

The 140 minute, 70 item SJT will judge how an applicant is likely to behave when encountering a similar situation as a foundation year 1 doctor and will replace the …
Initial Clinical Investigation of [18F]Tetrafluoroborate PET/CT in Comparison to [124I]Iodine PET/CT for Imaging Thyroid Cancer
Authors: Samuel Samnick, Ehab Al-Momani, Jan-Stefan Schmid, Anja Mottok, Andreas K. Buck, Constantin Lapa
Journal: Clinical Nuclear Medicine (2018)

Aim Recently, [ 18 F]tetrafluoroborate ([ 18 F]TFB) has been introduced as a versatile PET probe for imaging the human sodium/iodide symporter activity. This pilot study aimed to compare [ 18 F]TFB-PET/CT with [ 124 I]NaI-PET/CT imaging in thyroid cancer patients. Methods Nine patients with newly diagnosed differentiated thyroid cancer underwent both [ 18 F]TFB- and [ 124 I]NaI-PET/CT after total thyroidectomy. PET/CT scans were visually analyzed for the presence of remnant thyroid tissue and for metastatic lesions on a patient and lesion basis. For semiquantitative analysis, thyroid remnant/tumor to blood pool ratios were calculated. Results All patients presented with positive [ 18 F]TFB and [ 124 I]NaI-PET/CT scans. Retention of 124 I in remnant thyroid tissue was significantly higher as compared with [ 18 F]TFB ( P &lt; 0.01). In a lesion-based analysis, both tracers identified an almost equal number of foci with [ 18 F]TFB depicting a total of 41 foci and 124 I a total of 40 foci, respectively. In 6 of 9 patients, both radiopharmaceuticals returned an identical number of foci. Two 124 I-positive benign thyroid remnants were missed by [ 18 F]TFB-PET/CT in a single patient. In another case, both tracers identified different thyroid remnant tissues in the cervical region. Notably, [ 18 F]TFB demonstrated additional ( 124 I-negative) cervical lymph node metastases in 2 patients, leading to an overall agreement between the radiotracers of 91% (74/81 foci). Discussion In this pilot study, [ 18 F]TFB-PET was not inferior to [ 124 I]NaI-PET for detecting thyroid cancer and its metastases and was able to detect [ 124 I]NaI-PET-negative viable differentiated thyroid cancer metastases. Further clinical evaluation as a PET tracer for imaging thyroid pathophysiology and human sodium/iodide symporter expressing neoplasms is highly warranted.
Pulmonary capillary recruitment in exercise and pulmonary hypertension
Authors: David Langleben, Stylianos E. Orfanos
Journal: European Respiratory Journal (2018)

We read with interest the excellent European Respiratory Society statement on exercise pulmonary hypertension (PH) by Kovacs et al. [1] in the European Respiratory Journal . Fundamentally, exercise PH, especially with precapillary causes such as pulmonary arterial hypertension (PAH), is an inability of the lung circulation to accommodate increased blood flow during exercise. Although the authors mention "distention" of the vasculature, implying stretching of already perfused vessels, the increased pulmonary blood flow is primarily accommodated in the normal lung by recruitment of unused capillaries, allowing the pulmonary artery pressure to change minimally during exercise [2, 3]. Further evidence of this recruitment is found in true vasoresponders during an acute vasodilator challenge for evaluation of idiopathic PAH [4]. By contrast, because it is caused by precapillary vascular obstruction and not vasoconstriction, vasodilator-nonresponsive PAH accommodates any increased cardiac output via distention and not via recruitment [5]. We have also observed pulmonary capillary recruitment in normal humans during exercise (unpublished data). Recruitment is a normal physiological process, and it is impaired in many types of PH. As we move forward in our understanding of exercise PH and its physiology, precise definitions and semantics will be critical. Pulmonary capillary recruitment is important in the pulmonary haemodynamic response to exercise <http://ow.ly/tKJm30icJkp>
New drugs and perspectives for new anti-tuberculosis regimens
Authors: S. Tiberi, M. Muñoz-Torrico, R. Duarte, M. Dalcolmo, L. D’Ambrosio, G.-B. Migliori
Journal: Pulmonology (2018)

Tuberculosis (TB) is the ninth cause of global death, more than any other infectious disease. With growing drug resistance the epidemic remains and will require significant attention and investment for the elimination of this disease to occur. With susceptible TB treatment not changing over the last four decades and the advent of drug resistance, new drugs and regimens are required. Recently, through greater collaboration and research networks some progress with significant advances has taken place, not withstanding the comparatively low amount of resources invested. Of late the availability of the new drugs bedaquiline, delamanid and repurposed drugs linezolid, clofazimine and carbapenems are being used more frequently in drug-resistant TB regimens. The WHO shorter multidrug-resistant tuberculosis regimen promises to reach more patients and treat them more quickly and more cheaply. With this new enthusiasm and hope we this review gives an update on the new drugs and perspectives for the treatment of drug-susceptible and drug-resistant tuberculosis.
Physical Activity in Patients With Type 2 Diabetes: The Case for Objective Measurement in Routine Clinical Care
Authors: Nicole Oosterom, Christina M. Gant, Niels Ruiterkamp, Bert-Jan F. van Beijnum, Hermie Hermens, Stephan J.L. Bakker, Gerjan Navis, Miriam M.R. Vollenbroek-Hutten, Gozewijn D. Laverman
Journal: Diabetes Care (2018)

To perform at least 150 min of moderate-to-vigorous physical activity (MVPA) per week is a major aim in type 2 diabetes treatment (1), but actual measurements are not routinely performed in clinical practice. We questioned whether subjective assessment of physical activity is accurate to guide lifestyle advice.

We compared the results of the Short Questionnaire to Assess Health–Enhancing Physical Activity (SQUASH) (2) and the Fitbit Flex accelerometer (3) in 50 patients with type 2 diabetes included in the DIAbetes and LifEstyle Cohort Twente (DIALECT) trial, which was approved by the local institutional review board METC-Twente (NL57219.044.16) (4).

Patients wore the Fitbit for 7 consecutive days and were instructed to maintain their usual activities. Raw Fitbit data (steps/min) were organized into ready variables by an algorithm written in MATLAB (MathWorks, Natick, MA). MVPA was defined as ≥95 steps/min (5). Patients maintained a diary regarding activities not detected by the Fitbit …
Tumorspheres cultured from circulating epithelial tumor cells (CETCs) in pancreatic cancer patients having cancer stem cells properties and resistance to standard chemotherapeutics.
Authors: Monika Pizon, Dorothea Zimon, Ulrich A. Pachmann, Katharina Pachmann
Journal: Journal of Clinical Oncology (2015)

e22031 Background: Pancreatic cancer is the most aggressive and lethal cancer among all solid tumors. Over 90% of pancreatic cancers progress to become metastatic. The poor prognosis is due to the early dissemination via blood vessels and late detection of the tumor. Pancreatic cancer cells are relatively resistant to chemotherapy and radiation. CETCs are tumor cells that travel through the blood circulation and are responsible for the development of metastasis in distant organs. Only a small subpopulation of CETCs has the ability to generate metastasis. We established an effective method, tumorsphere growth, for identification of cancer stem cells circulating in the blood of patients with pancreatic cancer with subsequent phenotypic and genotypic characterization and testing for resistance to anti-cancer drugs. Methods: CETCs were enumerated with the maintrac approach and subsequently cultured under conditions favoring growth of tumorspheres. Stem cell markers and ALDH 1 activity was evaluated by fluorescence and gene expression analyses performed. To estimate the cytotoxic effect of drugs on tumorspheres we incubated them with conventional anticancer drugs in 48 hour culture in different concentrations and for different periods of time. Results: Only a small proportion of CETCs in pancreatic cancer patients has the ability to form tumorspheres. They display the typical phenotype of cancer stem cells and express high enzymatic activity for ALDH1. Array qRT-PCR analysis revealed that tumorspheres express genes of pluripotency such as SOX2, OCT4 and NANOG. The spheroids were chemoresistant to gemcitabine, irinotecan, oxaliplatin and 5-fluorouracil. Conclusions: These data demonstrate that tumorspheres derived from CETCs have cancer stem cells properties and are chemoresistant to the standard cytotoxic drugs used in pancreatic cancer therapy. Studying pancreatic cancer stem cells shows that the conventionally used drugs are ineffective against these cells explaining the low efficiency of chemotherapy in pancreatic cancer and may help researchers to identify targets for new drugs or therapies.
Long-Term Sirolimus for Primary Immunosuppression in Heart Transplant Recipients
Authors: Rabea Asleh, Alexandros Briasoulis, Walter K. Kremers, Rosalyn Adigun, Barry A. Boilson, Naveen L. Pereira, Brooks S. Edwards, Alfredo L. Clavell, John A. Schirger, Richard J. Rodeheffer, Robert P. Frantz, Lyle D. Joyce, Simon Maltais, John M. Stulak, Richard C. Daly, Jonella Tilford, Woong-Gil Choi, Amir Lerman, Sudhir S. Kushwaha
Journal: Journal of the American College of Cardiology (2018)
177Lu–Prostate-Specific Membrane Antigen Super Scan and Good Response Even After 1 Cycle of Radioligand Therapy
Authors: Kamran Aryana, Soroush Zarehparvar moghadam, Roham Salek, Ghasemali Divband
Journal: Clinical Nuclear Medicine (2018)

Abstract A 76-year-old man with castration-resistant prostate cancer and widespread skeletal metastases underwent 2 cycles of 177 Lu–prostate-specific membrane antigen (PSMA) 617 therapy in our department. Whole-body 177 Lu-PSMA scan after the first cycle showed diffuse skeletal PSMA-avid lesions, whereas no PSMA uptake was evident in the kidneys with minimal PSMA uptake by salivary glands (super scan). After 6 weeks, he received the second dose of 177 Lu-PSMA and whole-body scan after the treatment showed remarkable resolution of skeletal metastases and normal PSMA uptake by the kidneys and salivary glands. To our best knowledge, this is the first case report of 177 Lu-PSMA super scan.