tbuckley/cabot-search huggingface dataset:
Tumor-targeted Dual-modality Imaging to Improve Intraoperative Visualization of Clear Cell Renal Cell Carcinoma: A First in Man Study
Authors: Marlène C. Hekman, Mark Rijpkema, Constantijn H. Muselaers, Egbert Oosterwijk, Christina A. Hulsbergen-Van de Kaa, Otto C. Boerman, Wim J. Oyen, Johan F. Langenhuijsen, Peter F. Mulders
Journal: Theranostics (2018)

Intraoperative imaging with antibodies labeled with both a radionuclide for initial guidance and a near-infrared dye for adequate tumor delineation may overcome the main limitation of fluorescence imaging: the limited penetration depth of light in biological tissue.In this study, we demonstrate the feasibility and safety of intraoperative dual-modality imaging with the carbonic anhydrase IX (CAIX)targeting antibody 111 In-DOTA-girentuximab-IRDye800CW in clear cell renal cell carcinoma (ccRCC) patients.Methods: A phase I protein dose escalation study was performed in patients with a primary renal mass who were scheduled for surgery. 111In-DOTA-girentuximab-IRDye800CW (5, 10, 30, or 50 mg, n=3 ccRCC patients per dose level) was administered intravenously and after 4 days SPECT/CT imaging was performed.Seven days after antibody injection, surgery was performed with the use of a gamma probe and near-infrared fluorescence camera.Results: In total, fifteen patients were included (12 ccRCC, 3 CAIX-negative tumors).No study-related serious adverse events were observed.All ccRCC were visualized by SPECT/CT and localized by intraoperative gamma probe detection (mean tumor-to-normal kidney (T:N) ratio 2.5 ± 0.8), while the T:N ratio was 1.0 ± 0.1 in CAIX-negative tumors.ccRCC were hyperfluorescent at all protein doses and fluorescence imaging could be used for intraoperative tumor delineation, assessment of the surgical cavity and detection of (positive) surgical margins.The radiosignal was crucial for tumor localization in case of overlying fat tissue. Conclusion:This first in man study shows that tumor-targeted dual-modality imaging using 111 In-DOTA-girentuximab-IRDye800CW is safe and can be used for intraoperative guidance of ccRCC resection.
Acquisition of oocyte competence to develop as an embryo: integrated nuclear and cytoplasmic events
Authors: Marco Conti, Federica Franciosi
Journal: Human Reproduction Update (2017)

Infertility affects ~7% of couples of reproductive age with little change in incidence in the last two decades. ART, as well as other interventions, have made major strides in correcting this condition. However, and in spite of advancements in the field, the age of the female partner remains a main factor for a successful outcome. A better understanding of the final stages of gamete maturation yielding an egg that can sustain embryo development and a pregnancy to term remains a major area for improvement in the field. This review will summarize the major cellular and molecular events unfolding at the oocyte-to-embryo transition. We will provide an update on the most important processes/pathways currently understood as the basis of developmental competence, including the molecular processes involved in mRNA storage, its recruitment to the translational machinery, and its degradation. We will discuss the hypothesis that the translational programme of maternal mRNAs plays a key role in establishing developmental competence. These regulations are essential to assemble the machinery that is used to establish a totipotent zygote. This hypothesis further supports the view that embryogenesis begins during oogenesis. A better understanding of the events required for developmental competence will guide the development of novel strategies to monitor and improve the success rate of IVF. Using this information, it will be possible to develop new biomarkers that may be used to better predict oocyte quality and in selection of the best egg for IVF.
Neuropsychiatric adverse events of enzalutamide and abiraterone acetate: Meta-analysis of randomized clinical trials with real world reporting patterns from EudraVigilance.
Authors: Maria Paola Moreno Perez, Miguel Sanchez Iznaola, Angela Garcia, Jacobo Muñoz del Toro, Joaquin Casariego, Paul Robinson, Rafael Parra
Journal: Journal of Clinical Oncology (2018)

217 Background: Androgen deprivation is associated with cognitive decline and mood changes. Abiraterone acetate plus prednisone (AAP) and enzalutamide (ENZ) are oral hormonal agents for the treatment of metastatic castration resistant prostate cancer (mCPRC); both target the androgen signaling pathway. Meta-analysis for individual neuropsychiatric adverse effects (NAEs) associated with these drugs has not been available in the literature. Methods: Following the methodology presented by Ruiz et al. a further meta-analysis was performed to estimate the pooled Relative Risk (RR) of NAEs for AAP and ENZ. A complementary analysis of the EudraVigilance database was performed to explore the consistency of the real world adverse drug reactions (ADR) reporting pattern with the meta-analysis. Results: The meta-analysis results indicate that patients treated with ENZ had a statistically significant higher risk of restless leg syndrome (RLS), anxiety, headache and insomnia vs control. Both AAP and ENZ showed significant increased risk for falls vs control. The Proportional Reporting Ratio (PRR) of ADRs reported in Eudra is higher with ENZ than with AAP for all the variables analyzed. Conclusions: NAEs studied are more prevalent with ENZ vs placebo than AAP vs prednisone plus placebo. Reporting trend in Eudra is consistent with this results. [Table: see text]
Discrimination report is “call to action” for NHS, says chief executive
Authors: Matthew Limb
Journal: BMJ (2015)

A report highlighting the problem of workforce discrimination is a call to action for the NHS, Simon Stevens, chief executive of NHS England, has said. 

Speaking at the Managers in Partnership annual conference in London on 18 November, Stevens said that the report, produced by the healthcare think tank the King’s Fund, “paints an important picture of what is happening” and that it “represents a call to action for everyone in the …
Schedules for clinical assessment in neuropsychiatry
Authors: Faiz Rehman
Journal: BMJ (2011)

The schedules for clinical assessment in neuropsychiatry (SCAN) is a set of instruments, supported by manuals, that aim to measure and classify the psychopathology of the major psychiatric disorders of adult life.

SCAN has been developed by the World Health Organization over several years and is widely used, as evidenced by its translation into 35 or more languages.

To achieve robust levels of validity and reliability, SCAN is intended for use only by clinicians who have undertaken training at a World Health Organization designated SCAN training centre. There are 21 of these designated SCAN training and reference centres worldwide, five of which are in the United Kingdom. I attended …
Smooth muscle cell fate and plasticity in atherosclerosis
Authors: Sima Allahverdian, Chiraz Chaabane, Kamel Boukais, Gordon A Francis, Marie-Luce Bochaton-Piallat
Journal: Cardiovascular Research (2018)

Current knowledge suggests that intimal smooth muscle cells (SMCs) in native atherosclerotic plaque derive mainly from the medial arterial layer. During this process, SMCs undergo complex structural and functional changes giving rise to a broad spectrum of phenotypes. Classically, intimal SMCs are described as dedifferentiated/synthetic SMCs, a phenotype characterized by reduced expression of contractile proteins. Intimal SMCs are considered to have a beneficial role by contributing to the fibrous cap and thereby stabilizing atherosclerotic plaque. However, intimal SMCs can lose their properties to such an extent that they become hard to identify, contribute significantly to the foam cell population, and acquire inflammatory-like cell features. This review highlights mechanisms of SMC plasticity in different stages of native atherosclerotic plaque formation, their potential for monoclonal or oligoclonal expansion, as well as recent findings demonstrating the underestimated deleterious role of SMCs in this disease.
Caloric Restriction Engages Hepatic RNA Processing Mechanisms in Rhesus Monkeys
Authors: Timothy W. Rhoads, Maggie S. Burhans, Vincent B. Chen, Paul D. Hutchins, Matthew J.P. Rush, Josef P. Clark, Jaime L. Stark, Sean J. McIlwain, Hamid R. Eghbalnia, Derek M. Pavelec, Irene M. Ong, John M. Denu, John L. Markley, Joshua J. Coon, Ricki J. Colman, Rozalyn M. Anderson
Journal: Cell Metabolism (2018)
Glypican-1 as a novel immunotherapeutic target in prostate cancer.
Authors: Alexander Zaslavsky, Mackenzie Adams, Sandra Wissmueller, Douglas Campbell, Hans Klingemann, Brad Walsh, Ganesh S. Palapattu
Journal: Journal of Clinical Oncology (2018)

174 Background: New effective therapies for men with prostate cancer are desperately needed. Recently, cancer immunotherapy has emerged as an important new treatment strategy for prostate cancer and for castrate resistant prostate cancer (CRPC). Multiple studies have identified the heparan sulfate proteoglycan-1 Glypican 1 (GPC-1) as being overexpressed in different cancers, and also as being a possible marker of poor prognosis in several solid tumor cancers. GPC-1 has been recently identified as a potential marker for prostate cancer. The MIL-38 monoclonal antibody detects GPC-1 and an IgG1 chimeric version of this antibody has been developed for preclinical studies. Here we sought to examine MIL-38 binding to a panel of prostate cancer cell lines and examine its feasibility as a novel immunotherapeutic agent targeting GPC-1 in prostate cancer Methods: Expression of GPC-1 in CRPC cell lines was examined by Flow cytometry and Western Blotting using MIL-38 as the detector antibody. The competency of GPC-1 as an immunotherapeutic target was assessed via chimeric MIL-38 induced Antibody Dependent Cell Cytotoxicity (ADCC) using high affinity Natural Killer cells (haNKs) in vitro . Results: Flow cytometry and Western blot assessments of normal prostatic epithelial cells (i.e. RWPE-1) and cells from prostate cancer cell lines (i.e. PC-3, 22RV1, DU-145, VCaP, LNCaP, CWR-R1, and LAPC-4) revealed that only cancer cells expressed GPC-1. Enzalutamide resistant cell lines demonstrated higher expression of GPC-1 than their respective parental line. ADCC assays demonstrated enhanced haNK – prostate cancer cell cytotoxicity in the presence of chimeric MIL-38 anti-GPC-1 antibody, while the IgG1 isotype control had no effect. Conclusions: GPC-1 protein was expressed by most prostate cancer cell lines, including enhanced expression by enzalutamide resistant cells. Preliminary in vitro ADCC assay results revealed the potential utility of GPC-1 as an immunotherapeutic target in prostate cancer.
Doctors call for further industrial action in pension dispute
Authors: Helen Jaques
Journal: BMJ (2012)

Doctors at the BMA’s annual representative meeting have called for further industrial action in their dispute with the government over changes to the NHS pension scheme.

The association’s governing council, headed by its newly elected chairman, Mark Porter, has deferred a decision on the next steps on industrial action and is instead seeking an urgent meeting with Andrew Lansley, the health secretary for England, to discuss the dispute.

Porter said, “It was clear from the debates today that doctors remain angry at the government for tearing up a pensions deal reached only four years ago and that made the scheme sustainable for the future. Our preferred option has always been to find a fairer way forward through negotiation, and I want to explore that with the secretary of state for health.” Further industrial action is, however, a “possibility,” he added.

Representatives at the annual meeting agreed that the council should consider a range of options for further industrial action, including withdrawing from clinical commissioning, providing a Christmas Day style emergency only service in hospitals, and coordinating action with other unions.

Around a third of general practices and four in five hospitals were affected when doctors across the United Kingdom took industrial action for 24 hours on 21 June. …
RISK RECLASSIFICATION WITH ABSENCE OF CORONARY ARTERY CALCIUM AMONG STATIN CANDIDATES ACCORDING TO AMERICAN COLLEGE OF CARDIOLOGY/AMERICAN HEART ASSOCIATION (ACC/AHA) GUIDELINES: SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Gowtham Grandhi, Anshul Saxena, Tanuja Rajan, Emir Veledar, Amit Khera, Ron Blankstein, Roger Blumenthal, Leslee Shaw, Michael Blaha, Khurram Nasir
Journal: Journal of the American College of Cardiology (2018)
Prognostic value of the expression of immunomodulatory targets in surgically resected lung adenocarcinoma.
Authors: Kazuya Takamochi, Masaki Hosoya, Kaoru Mogushi, Takuo Hayashi, Hideya Kawaji, Yoshihide Hayashizaki, Kenji Suzuki
Journal: Journal of Clinical Oncology (2018)

173 Background: Therapies targeting immune checkpoints have recently shown encouraging activity in patients with non-small cell lung cancer. T-cell activation is controlled by the balance of co-stimulatory molecules that act positively in concert with T-cell receptor (TCR) signaling induced by antigen stimulation and co-inhibitory molecules (immune checkpoint molecules) that negatively regulate TCR signaling. Methods: We performed a Cap Analysis of Gene Expression (CAGE) analysis to quantify the gene expression of PD-L1, PD-L2, co-inhibitory molecules (CTLA-4, PD-1, TIM-3, BTLA, VISTA and LAG-3) and co-stimulatory molecules (CD28, OX40, GITR, CD317, CD27 and HVEM) using RNA extracted from 71 frozen tumor tissue samples of surgically resected lung adenocarcinomas, including 35 EGFR-mutated, 11 KRAS-mutated and 25 wild-type tumors. The correlations between the expression of the above immunomodulatory targets and the overall survival were analyzed. None of patients received immunotherapy. Results: Lung adenocarcinomas in this study were divided into two groups: tumors showing high expression of almost all immunomodulatory targets and those with low expression. The expression of CTLA-4, PD-1 and PD-L1 was not prognostic. The prognosis of patients with tumors showing high expression of TIM-3 was significantly worse than that of those with low expression, regardless of the EGFR and KRAS mutation status. The prognosis of patients with tumors showing high expression of VISTA was significantly better than that of those with low expression, regardless of the EGFR and KRAS mutation status. The prognosis of patients with tumors showing high expression of LAG-3 was significantly worse than that of those with low expression among overall patients. However, high expression of LAG-3 was an unfavorable prognostic factor in patients with EGFR-mutated or wild-type tumors, and it was a favorable prognostic factor in patients with KRAS-mutated tumors. Conclusions: Lung adenocarcinomas may be divisible into immunogenic and nonimmunogenic tumors. The prognostic value differs according to the immunomodulatory target and driver oncogene status.
Evidence on GP workforce “crisis” is presented to BMA
Authors: Abi Rimmer
Journal: BMJ (2014)

Members of BMA subcommittees have presented the association with a roundup of evidence outlining the scale of the “crisis” facing the GP workforce.

In a draft paper submitted to the BMA’s General Practitioners Committee (GPC) and seen by BMJ Careers, three GPs who sit on the association’s subcommittees warned about the effects on the specialty of falling recruitment and the imminent retirement of many older GPs.

“The GP workforce crisis, which has been talked about in worried, hushed tones for the last few years, has finally arrived in 2014,” the paper said. “We must start listening to tomorrow’s workforce to continue the path of innovation that has served …
Second Annual Go Red for Women Issue
Authors: Sharon C. Reimold, Joseph A. Hill
Journal: Circulation (2018)

n the United States, 1 in 4 women dies from heart disease. 1 Although this sad statistic is widely-although not universally-recognized in the cardiovascular healthcare profession, it is less well known in the nonmedical, lay community.Indeed, most noncardiologist healthcare providers do not know this either.Although evidence suggests that awareness is increasing among women through efforts such as Go Red for Women, the majority remains unaware that the single greatest risk to their health and longevity derives from heart disease.Why is that?Undoubtedly, the reasons are multifactorial.First, we have done an insufficient job of educating the lay population of the realities of heart disease in women.Second, other advocacy groups have had great success in highlighting the stark realities of their disease of focus.You only have to turn on a National Football League game in October to see pink shoes and gloves, all designed to raise awareness of the tragedies of breast cancer.Good for advocacy efforts on behalf of these other tragic diseases!We, in the realm of cardiovascular disease, can learn a great deal from these programs; indeed, we must.Other reasons include the fact that heart disease can sometimes present in women in ways distinct from the stereotypical symptoms with which all are familiar.Women are more likely than men are to report multiple symptoms at the time of presentation of an acute coronary syndrome.When this happens, patients, family members, and healthcare providers are often less clear that the heart is the source of the problem.Apart from doing a better job of educating the lay public (and other providers), what else can we do to address these challenges?First, we can remind ourselves, as well as relevant regulatory and funding agencies, that the biology of the female organism is distinct from that of the male in many ways well beyond the reproductive tract.Indeed, the realities of sexual dimorphism in the human myocardium are becoming increasingly clear.In fact, some would say that sex-based biological differences are at least as robust-possibly more robust-in the heart than in other organs.Whereas much of the biology of cardiovascular disease is shared between men and women, we, as cardiovascular practitioners and investigators, must redouble our efforts to dissect sex-based differences to tackle the realities of heart disease in women.As part of this effort, the fact that females are significantly underrepresented in cardiovascular research, both preclinical and clinical, must be rectified.The present issue of Circulation represents the second of our Go Red for Women issues designed specifically to explore and dissect mechanisms, clinical presentations, diagnostic strategies, and therapeutic approaches with direct relevance to women with-or at risk for-heart disease.The issue includes articles on pregnancy, spontaneous preterm delivery, and preeclampsia, and their impact on cardiovascular health.Other articles focus on female sex and ischemic
Caution to Readers About Systematic Review on Vitamin K and Prevention of Fractures That Included Problematic Trials
Authors: David J. Torgerson
Journal: JAMA Internal Medicine (2018)

To the Editor On behalf of my coauthors, I write to alert readers about the following article, "Vitamin K and the Prevention of Fractures: Systematic Review and Meta-analysis of Randomized Controlled Trials."1
Plasma cell output from germinal centers is regulated by signals from Tfh and stromal cells
Authors: Yang Zhang, Laura Tech, Laura A. George, Andreas Acs, Russell E. Durrett, Henry Hess, Lucy S.K. Walker, David M. Tarlinton, Anne L. Fletcher, Anja Erika Hauser, Kai-Michael Toellner
Journal: The Journal of Experimental Medicine (2018)

Germinal centers (GCs) are the sites where B cells undergo affinity maturation. The regulation of cellular output from the GC is not well understood. Here, we show that from the earliest stages of the GC response, plasmablasts emerge at the GC–T zone interface (GTI). We define two main factors that regulate this process: Tfh-derived IL-21, which supports production of plasmablasts from the GC, and TNFSF13 (APRIL), which is produced by a population of podoplanin+ CD157high fibroblastic reticular cells located in the GTI that are also rich in message for IL-6 and chemokines CXCL12, CCL19, and CCL21. Plasmablasts in the GTI express the APRIL receptor TNFRSF13B (TACI), and blocking TACI interactions specifically reduces the numbers of plasmablasts appearing in the GTI. Plasma cells generated in the GTI may provide an early source of affinity-matured antibodies that may neutralize pathogens or provide feedback regulating GC B cell selection.
Nearly 97% of applicants to 2014 foundation programme have been allocated
Authors: Abi Rimmer
Journal: BMJ (2014)

The UK Foundation Programme Office (UKFPO) has announced that 7114 applicants (96.6%) to the 2014 foundation programme have been allocated to a foundation school.

Just over 92% of applicants got into one of their top five schools, and 82% were allocated to one of their top two choices, the UKFPO said.

In January UKFPO said …
‘Deep Koebner’ phenomenon of the flexor tendon-associated accessory pulleys as a novel factor in tenosynovitis and dactylitis in psoriatic arthritis
Authors: Ilaria Tinazzi, Dennis McGonagle, Sibel Zehra Aydin, Donatella Chessa, Antonio Marchetta, Pierluigi Macchioni
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objectives</h3> Skin and joint involvement in psoriasis (PsO) and psoriatic arthritis (PsA) are thought to relate to the so-called Koebner response. Given that dactylitis is non-randomly distributed in the digits, this study tested the hypothesis that the accessory pulleys linked to the flexor tendons were thickened in PsA and thus exhibited koebnerisation. <h3>Methods</h3> Ninety-six subjects (27 PsA, 27 rheumatoid arthritis (RA), 23 PsO and 19 healthy controls (HCs)) were enrolled. The A1, A2 and A4 pulley thickness was measured using a high-resolution probe (22 MHz). All patients were in remission or low disease activity with current dactylitis being excluded. <h3>Results</h3> Within 864 pulleys investigated, patients with PsA had thicker pulleys in every digit compared with both RA (P&lt;0.001 and P=0.003) and HCs (P&lt;0.001). RA and PsO groups had some pulleys in some digits thicker than HCs whereas some others were comparable. The second digit A1 pulley thickness was higher in patients with PsA with previous dactylitis (P=0.020). More pulleys were thickened in the PsA group (165/243, 68%) than RA (41/243, 17%; P&lt;0.001) and HCs (13/171, 7.6%; P&lt;0.001). <h3>Conclusions</h3> In established PsA, the accessory pulleys are thickened compared with RA, PsO or HCs and especially in subjects with a history of dactylitis. These findings implicate the involvement of pulleys in PsA-related tenosynovitis and dactylitis supporting the idea of deep koebnerisation in dactylitis and sites of high physical stress.
PREVALENCE AND PREDICTORS OF LONG-TERM TARGET VESSEL AND NON-TARGET VESSEL MYOCARDIAL INFARCTION AFTER PCI: A PATIENT LEVEL ANALYSIS INTEGRATING DATA FROM 12 CLINICAL TRIALS
Authors: Yuqi Fan, Akiko Maehara, Yiran Zhang, Pieter Smits, Clemens von Birgelen, Martin B. Leon, Patrick Serruys, Ori Ben-Yehuda, Gary Mintz, Gregg Stone
Journal: Journal of the American College of Cardiology (2018)
Gaps in trainee rotas cause patient safety problems, say consultants
Authors: Abi Rimmer
Journal: BMJ (2016)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Gaps in trainee rotas cause patient safety problems, say consultants Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.