tbuckley/cabot-search huggingface dataset:
Clinical management course for staff and associate specialist doctors
Authors: Imran Mushtaq, Rizwana Jafry
Journal: BMJ (2009)

Keele University’s clinical management course has been specially developed to meet the needs of staff grade (now specialty) doctors and associate specialist (SAS) doctors in the NHS. The course is intended to help prepare these doctors for a move to consultant posts, and it helps to give a deeper insight into NHS management issues for doctors who are considering article 14 application (certificate of eligibility for specialist registration) to join the General Medical Council’s specialist register. It is not specialty specific and is built on Keele University’s experience of providing clinical management courses for specialist registrars.

Before the course, which was a three …
“Only a matter of time” until local pay is applied to doctors
Authors: Helen Jaques
Journal: BMJ (2012)

Locally determined pay for doctors in England is “only a matter of time” but would inhibit the free movement of doctors around the UK, have a negative effect on the training of junior doctors, and create recruitment problems in deprived areas, doctors have said.

Delegates at the BMA’s annual representative meeting agreed that the association should campaign to maintain national contracts for doctors but stopped short of mandating its governing council to ballot on strike action if local negotiations on pay are imposed.

The government is conducting a review of locally determined “market facing” pay for NHS staff on the Agenda for …
Spine safe course for surgeons
Authors: Muhammad Imran Ul Haq
Journal: BMJ (2009)

The spine safe course is run by the trauma and orthopaedics department at Leeds General Infirmary, and the emphasis is on the safe management of acute spinal pathology. The course focuses on developing an understanding of the basic principles behind spine biomechanics; acute spinal injuries; fracture fixation; learning how to plan management; and acquiring the necessary practical skills to assess spinal trauma. The course is held every June in the Leeds General Infirmary.

The course is aimed at surgical trainees who wish to pursue a career in trauma and orthopaedics or in accident and emergency and is for those who deal with spinal trauma. Most of the participants have passed their membership examinations of the Royal College of Surgeons and have more than six months’ experience in trauma and orthopaedics or accident and emergency. Most of the candidates were surgical trainees from the Yorkshire School of Surgery.

Participants are encouraged to have attended …
THE CLOSURE OF PATENT FORAMEN OVALE REDUCES RISK OF RECURRENT STROKE OR TRANSIENT ISCHEMIC STROKE IN SELECT PATIENTS WITH CRYPTOGENIC STROKE: A META-ANALYSIS OF RANDOMIZED CONTROL TRIALS
Authors: Sukhchain Singh, Varun Kumar, Daniela Kovacs, Sandeep Khosla, Rohit Arora
Journal: Journal of the American College of Cardiology (2018)
Eosinophilic inflammation of the paranasal sinuses and reduced nasal nitric oxide levels in patients with chronic rhinosinusitis
Authors: Kanako Yoshida, Tetsuji Takabayashi, Masafumi Sakashita, Yoshimasa Imoto, Norihiko Narita, Shigeharu Fujieda
Journal: Journal of Allergy and Clinical Immunology (2018)
Finding the brake: dissecting the RhoA pathway regulating glioma cell migration
Authors: Sophie Taylor, Sabine Knipp, Georgia Mavria, John Ladbury, Anke Brüning-Richardson, Susan Short
Journal: Neuro-Oncology (2018)

Cell migration is one of the hallmarks of cancer. Cancer cells can adopt two main migratory strategies displaying either a mesenchymal or amoeboid phenotype. Targeting cell migration presents an opportunity in improving treatment of invasive and migratory tumours, however the cellular mechanisms that control the cell migration phenotypes in high-grade gliomas, such as Glioblastoma multiforme, are still not fully understood. In previous work we used 2D and 3D migration assays to screen a panel of inhibitors targeting the actin polymerisation pathway, a key regulator of cell migration in glioma. Amongst RhoA pathway inhibitors, which are key negative regulators of migration, we have identified one compound, CCG-1423, that uniquely failed to inhibit migration. CCG-1423 induces a reduced expression of the adhesion protein CCN1 by blocking nuclear import of MKL-1, a transcriptional co-activator. We suggest that CCG-1423 induces a mesenchymal transition, which permits continued migration. To confirm the effect of CCG-1423 on CCN1 levels we used ELISA to detect secreted CCN1 levels in culture supernatants in treated and non-treated U251 and U87 cells. CCG-1423 significantly reduced CCN1 levels in supernatant of both cell lines compared to untreated controls. Further biochemical analysis was performed to establish levels of MKL-1 in treated versus untreated cells and to elucidate its association with other proteins. Preliminary data indicate an increase in MKL-1 concentration in treated cells, consistent with a build-up of MKL-1 in the cytosol due to lack of nuclear import, as previously reported. Further detailed characterisation of the RhoA signalling pathway in glioma will provide an understanding of the role of MKL-1 in mesenchymal migration and the effect of CCG-1423 on mesenchymal switching. We will next characterise the interactions between CCG-1423 and MKL-1, and use pharmacological and/or genetic manipulation to refine combination treatments to target both mesenchymal and amoeboid cell migration.
Public health officials can’t get data they need, says PHE
Authors: Matthew Limb
Journal: BMJ (2016)

Public health directors cannot access the data they need to do their jobs, Public Health England has said.

John Newton, chief knowledge officer for Public Health England, told the House of Commons Health Committee on 7 June that lack of data made it harder to do “ad hoc” public health research locally. Sarah Wollaston, chair of the committee, said that this was a cause for concern.

Newton said that public health directors had difficulty getting access to data concerning their populations on healthcare activity, such as hospital episode statistics and emergency department data. They also had problems obtaining operational data …
ANP32A regulates histone H3 acetylation and promotes leukemogenesis
Authors: Xuejing Yang, Bin Lu, Xueqin Sun, Cuijuan Han, Chunling Fu, Kailin Xu, Min Wang, Dengju Li, Zhichao Chen, Puneet Opal, Qiang Wen, John D. Crispino, Qian-fei Wang, Zan Huang
Journal: Leukemia (2018)
BIOENGINEERING SILICON QUANTUM DOT THERANOSTICS USING A NETWORK ANALYSIS OF METABOLOMIC AND PROTEOMIC DATA IN CARDIAC ISCHAEMIA
Authors: Patrick Gladding, Folarin Erogbogbo, Mark Swihart, Katie Smart, Ralph Stewart, Irene Zeng, Mia Jullig, Katherine Bakeev, Raphael Hu, Stefan Schliebs, Banu Gopalan, Seif El-Jack
Journal: Journal of the American College of Cardiology (2012)
LLM/Diploma in mental health law
Authors: Christine Kennedy
Journal: BMJ (2004)

Practising lawyers, psychiatrists, social workers, hospital managers, and law graduates, as well as those with a general interest in mental health law. It provides a unique opportunity for psychiatrists to gain a postgraduate qualification while still pursuing their careers.

1999-2001, during the first two years of specialist registrar training in forensic psychiatry. The course has become increasingly popular with forensic psychiatry trainees in particular, but can benefit any psychiatrist in the United Kingdom.

Mainly out of interest, but I would also consider it to be essential training to get a handle on understanding how the law thinks and operates in the different interfaces with psychiatry (for example, mental health review tribunals, …
Clinical significance of humoral immunity against XAGE1 cancer-testis antigen in lung adenocarcinoma.
Authors: Mikio Oka, Koji Kurose, Midori Isobe, Minoru Fukuda, Yoshihiro Ohue
Journal: Journal of Clinical Oncology (2018)

162 Background: Cancer-testis antigens (CTAs) are expressed predominantly in the testis and various types of cancer. Some of CTAs are highly immunogenic and attractive targets for cancer immunotherapy. We identified XAGE1 as a dominant CTA in lung adenocarcinoma (LAD). In this study, we examined immune responses to XAGE1 and the clinical significance in LAD patients. Methods: Expression of XAGE1 and immune checkpoint molecules in LAD tissues was determined by immunohistochemistry. The XAGE1 antibody and T cell immune responses were analyzed in blood samples. Then, overall survival (OS) of the XAGE1 antigen-positive and -negative, and XAGE1 antibody-positive and -negative patients was analyzed. Results: The XAGE1 antigen was expressed in approximately 40% of LAD, and the expression reflected shortened OS of pStage I-IIIA LAD in two japanese cohorts. In addition, expression profiles of XAGE1 and immune checkpoint molecules of PD-L1 and galectin-9 on tumor cells efficiently predicted OS of pStage I-IIIA LAD patients. The XAGE1 antibody response was observed in 6% (9/155) of our pStage I-IIIA, and 20% (34/167) of cStage IIIB-IV LAD, respectively, showing a higher antibody response rate in more advanced stages. In the antibody-positive patients, CD4 and CD8 T cell responses were frequently elicited, and phenotypic and functional analyses of T cells indicated immune activation. Furthermore, the OS of antibody-positive patients significantly prolonged as compared with that of antibody-negative patients with either XAGE1 antigen-positive EGFRwt (31.5 vs 15.6 months, P = 0.05) or EGFRmt (34.7 vs 11.1 months, P = 0.001) LAD. Multivariate analysis showed that the XAGE1 antigen expression was a worse predictor in EGFRmt LAD (HR: 5.23). On the other hand, the presence of the XAGE1 antibody was a strong predictor for prolonged OS in XAGE1 antigen positive LAD (HR: 0.18) and in either EGFRwt or EGFRmt LAD. Conclusions: The XAGE1 antigen induced strong immune responses in LAD patients with more advanced stages, and the production of XAGE1 antibody in these patients showed good prognosis. Our results indicate that the XAGE1 immunity is probably a good prognostic biomarker in LAD and a promising target for immunotherapy of LAD.
Clinical significance of high expression of a specific solute carrier transporter in HCC.
Authors: Patricia Gifu, Sonia Brun, Guanxiong Wang, Firas Bassissi, Claude Caron de Fromentel, Philippe Merle, Philippe Halfon
Journal: Journal of Clinical Oncology (2018)

303 Background: Hepatocellular carcinoma (HCC) is the third cause of cancer-related death. GNS561 (Genoscience Pharma, France) is a small molecule inducing apoptosis by lysosome inhibition and caspase activation. GNS561 has high hepatotropism and anti-tumorigenic capacity on tumor bulk and cancer stem cells. Its main target is a specific solute carrier transporter (SLCt). We describe here the clinical relevance of the overexpression of SLCt in HCC patients. Methods: The expression of SLCt was investigated by iQRT-PCR in surgically resected HCC tumors (T) and the matched non-tumor (NT) liver tissues (n=180) as well as healthy livers (HL) devoid of chronic or acute disease (n=10). Pearson's chi-squared test was employed for significant correlation tests while univariate and multivariate survival analysis were performed by Cox proportional hazard ratio (HR) method. Results: SLCt was overexpressed in 40.5% of T and 30.3% of NT as compared to HL. High SLCt in T was associated with microvascular emboli (p=0.034) and expression of the cancer stem cell markers Sox2 (p=0.025) and CD133 (p=0.034). High SLCt in NT correlated with cirrhosis (p=0.009) and presence of satellite nodules (p&lt;0.001). Univariate analysis showed association between high SLCt in T and shortened overall survival (OS) (HR=1.08, p=0.020), lower progression-free survival (PFS) (HR=1.76, p=0.006) as well as early recurrence-free survival (ERFS) (within 2 years post-surgery) (HR=1.88, p=0.008). In multivariate analysis, high SLCt tended to be an independent factor for OS, and this was strongly significant for PFS and ERFS. High SLCt in NT, is quite a poor outcome factor on late recurrence-free survival (HR=2.33, p=0.056) together with cirrhosis in univariate analysis, but remained dependent of cirrhosis in multivariate analysis. Late recurrence is linked to the intrinsic tumorigenic status of the liver. Conclusions: Overexpression of the SLCt in HCC tumors is associated to stemness features and appears as a poor outcome factor impacting on early recurrence. Further, SLCt in NT is associated with development of de-novo HCC. Validation cohorts and prospective assessments are needed to define high SLCt as a potential biomarker of HCC stemness and patient outcome.
LEFT ATRIAL VENO-ARTERIAL EXTRACORPOREAL MEMBRANE OXYGENATION: PERCUTANEOUS BI-ATRIAL DRAINAGE TO AVOID PULMONARY EDEMA IN PATIENTS WITH LEFT VENTRICULAR SYSTOLIC DYSFUNCTION
Authors: Kenneth Dulnuan, Maya Guglin, Joseph Zwischenberger, John Gurley
Journal: Journal of the American College of Cardiology (2018)
Leading the surgical ward round
Authors: Adel Fattah
Journal: BMJ (2005)

CXCL14 is a relatively new chemokine with unidentified receptor and undefined function. Recently, we found that CXCL14 is upregulated in arthritic joints in a mouse model of autoimmune arthritis, collagen-induced arthritis. To examine the role of CXCL14 in the development and pathogenesis of autoimmune arthritis, we have generated transgenic (Tg) mice that overexpress CXCL14 under control of phosphoglycerate kinase promoter. The results showed that CXCL14-Tg mice developed more severe arthritis compared with wild-type controls. The draining lymph nodes of CXCL14-Tg mice were significantly enlarged and contained an increased number of activated T cells, particularly the CD44<sup>+</sup>CD62L<sup>low</sup> effector memory cells. In addition, T cells from CXCL14-Tg mice exhibited an enhanced proliferative response against collagen II and produced higher levels of IFN-γ but not IL-4 or IL-17. CXCL14-Tg mice also had elevated levels of IgG2a autoantibodies. These findings indicated that CXCL14 plays an important role in the autoimmune arthritis, which may have an implication in understanding the pathogenic mechanisms of rheumatoid arthritis in humans and, ultimately, therapeutic interference.
COMPENSATORY MECHANISMS MAINTAINING CARDIAC FUNCTION IN HCM SUBJECTS: RELATIONSHIP BETWEEN SEMI QUANTITATIVE MYOCARDIAL FIBROSIS VOLUME ON CMR AND LEFT VENTRICULAR EJECTION FRACTION, STRAIN, WALL THICKENING AND SIZE ON TTE
Authors: Nobusada Funabashi, Koya Ozawa, Hiroyuki Takaoka, Gentaro Koyama, Yoshio Kobayashi
Journal: Journal of the American College of Cardiology (2018)
The Wnt/β‐catenin pathway determines the predisposition and efficiency of liver‐to‐pancreas reprogramming
Authors: Helit Cohen, Hila Barash, Irit Meivar‐Levy, Kfir Molakandov, Marina Ben‐Shimon, Michael Gurevich, Fatima Zoabi, Adi Har‐Zahav, Rolf Gebhardt, Frank Gaunitz, Michael Gurevich, Eytan Mor, Philippe Ravassard, Shoshana Greenberger, Sarah Ferber
Journal: Hepatology (2018)

Transdifferentiation (TD) is the direct reprogramming of adult cells into cells of alternate fate and function. We have previously shown that liver cells can be transdifferentiated into beta‐like, insulin‐producing cells through ectopic expression of pancreatic transcription factors (pTFs). However, the efficiency of the process was consistently limited to &lt;15% of the human liver cells treated in culture. The data in the current study suggest that liver‐to‐pancreas TD is restricted to a specific population of liver cells that is predisposed to undergo reprogramming. We isolated TD‐predisposed subpopulation of liver cells from &gt;15 human donors using a lineage tracing system based on the Wnt response element, part of the pericentral‐specific promoter of glutamine synthetase. The cells, that were propagated separately, consistently exhibited efficient fate switch and insulin production and secretion in &gt;60% of the cells upon pTF expression. The rest of the cells, which originated from 85% of the culture, resisted TD. Both populations expressed the ectopic pTFs with similar efficiencies, followed by similar repression of hepatic genes. Our data suggest that the TD‐predisposed cells originate from a distinct population of liver cells that are enriched for Wnt signaling, which is obligatory for efficient TD. In TD‐resistant populations, Wnt induction is insufficient to induce TD. An additional step of chromatin opening enables TD of these cells. Conclusion: Liver‐to‐pancreas TD occurs in defined predisposed cells. These cells' predisposition is maintained by Wnt signaling that endows the cells with the plasticity needed to alter their transcriptional program and developmental fate when triggered by ectopic pTFs. These results may have clinical implications by drastically increasing the efficacy of TD in future clinical uses. (H epatology 2018).
Emergency doctor who lied at nurse’s tribunal is struck off
Authors: Clare Dyer
Journal: BMJ (2018)

A locum staff grade doctor in an emergency department who lied under oath at a Nursing and Midwifery Council (NMC) hearing to try to deflect blame over a young patient’s death has been struck off the UK medical register.

Imran Ali Tabrizi testified in May 2014, describing events before the death of an Essex University student who had fallen down stairs while intoxicated in October 2011. The hearing examined the role of nurse Doreen Castleton, the sister in charge of the emergency department at Colchester Hospital that night, where Tabrizi was on duty.

Ambulance staff transporting the 18 year old student to the hospital had called ahead with a “pre-alert,” which warns staff that they might need to prepare a trauma team for the …
Female doctors who work long hours are more likely to get divorced, US researchers say
Authors: Abi Rimmer
Journal: BMJ (2015)

Female doctors who work more than 40 hours a week are more likely to get divorced than those who work less, US researchers have found. The researchers, led by Anupam Jena at Harvard Medical School’s department of healthcare policy, also found that female doctors had a “substantially higher prevalence” of divorce than male doctors.

The researchers used data collected between 2008 …
GP trainees in Wales to be centrally employed
Authors: Abi Rimmer
Journal: BMJ (2015)

GP trainees in Wales are set to be centrally employed by a single organisation, the Welsh government has announced.

Mark Drakeford, minister for health and social services, said that all GP trainees in Wales would be employed by NHS Wales Shared Services Partnership rather than by individual practices. He said that this was part of wider plans to encourage more doctors to work in general practice.

Under the old …
Rituximab Maintenance Therapy Reduces Rate of Relapse of Pancreaticobiliary Immunoglobulin G4-related Disease
Authors: Shounak Majumder, Sonmoon Mohapatra, Ryan J. Lennon, Guilherme Piovezani Ramos, Neil Postier, Ferga C. Gleeson, Michael J. Levy, Randall K. Pearson, Bret T. Petersen, Santhi Swaroop Vege, Suresh T. Chari, Mark D. Topazian, Thomas E. Witzig
Journal: Clinical Gastroenterology and Hepatology (2018)
PHYSICAL FUNCTION, QUALITY OF LIFE, AND DEPRESSION IN ELDERLY, HOSPITALIZED PATIENTS WITH ACUTE DECOMPENSATED HEART FAILURE WITH PRESERVED VERSUS REDUCED EJECTION FRACTION: ANALYSIS FROM THE REHAB-HF TRIAL
Authors: Haider Warraich, Dalane Kitzman, David Whellan, Duncan Pamela, Robert Mentz, Amy Pastva, Ben Nelson, Gordon Reeves
Journal: Journal of the American College of Cardiology (2018)
Abstract P4-04-08: Therapeutic strategy for ERα mutation driven-endocrine resistance in ER-positive breast cancers
Authors: J-A Kim, SAW Fuqua
Journal: Cancer Research (2018)

Abstract Background: Although estrogen receptor (ER)-positive breast cancers are treated with endocrine therapy, 25% of these patients are at risk of relapse and the development of acquired endocrine resistance. Recently mutations in the ER gene (ESR1) have been identified which induce resistance to endocrine therapy. The most frequent ESR1 mutation, Y537S, promotes ligand-independent ER activity. It is known that ER regulates the cell cycle in a ligand-dependent manner. In this study, we examined the effects of the Y537S ESR1 mutation on cell cycle signaling and therapeutic response to checkpoint inhibitor. Material and Methods: MCF-7 cells expressing the Y537S ESR1 mutation were generated by CRISPR-Cas9 knock-in techniques. Cells were incubated in phenol red minus medium containing 5% charcoal-dextran treated serum for 5 days to remove exogenous hormones. Cell cycle and apoptosis were examined by Flow cytometry and Annexin-V assays. Proliferation was analyzed by BrdU incorporation. Cell senescence was determined using beta-galactosidase assays. Cell cycle checkpoint kinases were examined by western blot analysis. Cell growth was analyzed using soft agar or MTT assays. Results: Levels of p53 and apoptosis pathway proteins were significantly elevated in Y537S ESR1 mutant cells using RNA expression and reverse-phase protein microarrays. The ATM/ATR and Chk1/Chk2 mediated checkpoint signaling, the upstream pathway of p53, was activated in ESR1 Y537S mutation, which was repressed with fulvestrant treatment. ESR1 Y537 mutant cells accumulated about 5 fold in S phase and 1.7 fold in G2/M phase compared to control cells in estrogen deprived (ED) condition. BrdU incorporation was also increased about 2.5 fold compared with parental cells in estrogen-free medium. In addition, ESR1 Y537 mutant cells expressed a DNA double-strand break marker, gamma-H2AX protein in ED condition. Apoptosis and senescence were observed in ESR1 Y537S mutant cells in regular medium, however, apoptosis was not shown in ED medium. Chk1 inhibitor, PF477736 sensitized MCF-7 expressing ESR1 Y537S mutation to endocrine treatments such as fulvestrant, tamoxifen and AZD9496. Conclusion: Combination therapy with cell cycle checkpoint kinase inhibitor may lead better prognosis in ER mutation driven-endocrine resistance in postmenopausal breast cancers. Citation Format: Kim J-A, Fuqua SAW. Therapeutic strategy for ERα mutation driven-endocrine resistance in ER-positive breast cancers [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-04-08.