tbuckley/cabot-search huggingface dataset:
Diffusion-weighted MRI may support the identification of non-enhancing IDH wildtype astrocytoma
Authors: Stefanie Thust, Sotirios Bisdas, Jeremy Rees, Harpreet Hyare, Sebastian Brandner, Sara Hassnein, H Rolf Jager, Almas Siddiqui, Laura Mancini
Journal: Neuro-Oncology (2018)

To determine if apparent diffusion coefficient (ADC) measurements permit the distinction of non-enhancing IDH mutant (IDHmut) from IDH wildtype (IDHwt) astrocytoma. Lack of Gadolinium contrast enhancement represents a typical feature of low grade astrocytomas, but is increasingly considered an unreliable predictor of non-aggressive behaviour. The latest World Health Organisation (WHO) classification recognises a distinct subgroup of rapidly progressive gliomas (IDHwt astrocytoma) without histopathological grade IV characteristics. On molecular grounds, IDHwt astrocytomas constitute malignant neoplasms and are suspected to represent early glioblastomas (GBM). Their histology may be matched by initially innocuous imaging appearances, which could lead to misdiagnosis if a ‘watch and wait’ approach is adopted. From a cohort of 58 WHO grade II/III astrocytomas (34 IDHwt/24 IDHmut), 22 non-enhancing tumours were selected. Manually obtained T2w volumetric segmentation masks were spatially registered (FSL) to ADC maps derived from standard DWI (b0-b1000). A quantitative analysis of diffusion values was performed blinded to molecular data and compared (Student’s t-test) for both groups. 13 IDHwt (6 WHO II/7 WHO III) and 9 IDHmut (6 WHO II/3 WHO III) astrocytomas were analysed. Maximum, mean and minimum ADC values for the IDHwt group were significantly lower (p < 0.01) than for the IDHmut group. CONCLUSION: ADC values derived from clinical DWI may reveal the aggressive nature of non-enhancing IDHwt astrocytomas, whereby mean ADC measurements are obtainable on most hospital imaging systems. Further study is required to determine, if a threshold value can be defined and to consider potential influences from WHO grade.
As a house officer how should I apply for an elective attachment at a hospital in the UK?
Authors: Jo Constable
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>
RIPK1 Binds MCU to Mediate Induction of Mitochondrial Ca2+ Uptake and Promotes Colorectal Oncogenesis
Authors: Fanxin Zeng, Xiao Chen, Weiyi Cui, Wei Wen, Fujian Lu, Xueting Sun, Dongwei Ma, Ye Yuan, Zezhong Li, Ning Hou, Hong Zhao, Xinyu Bi, Jianjun Zhao, Jianguo Zhou, Yan Zhang, Rui-Ping Xiao, Jianqiang Cai, Xiuqin Zhang
Journal: Cancer Research (2018)

The receptor-interacting protein kinase 1 (RIPK1) is an essential signaling molecule in pathways for cell survival, apoptosis, and necroptosis. We report here that RIPK1 is upregulated in human colorectal cancer and promotes cell proliferation when overexpressed in a colon cancer cell line. RIPK1 interacts with mitochondrial Ca2+ uniporter (MCU) to promote proliferation by increasing mitochondrial Ca2+ uptake and energy metabolism. The ubiquitination site of RIPK1 (RIPK1-K377) was critical for this interaction with MCU and function in promoting cell proliferation. These findings identify the RIPK1-MCU pathway as a promising target to treat colorectal cancer.Significance: RIPK1-mediated cell proliferation through MCU is a central mechanism underlying colorectal cancer progression and may prove to be an important therapeutic target for colorectal cancer treatment. Cancer Res; 78(11); 2876-85. ©2018 AACR.
Homelessness and public health
Authors: Mark Fransham, Danny Dorling
Journal: BMJ (2018)

The number of people officially recorded as sleeping on the streets of England rose from 1768 in 2010 to 4751 in autumn 2017. Charities estimate the true figure to be more than double this. There has also been an increase in homeless families housed by local authorities in temporary accommodation, rising from 50 000 in 2010 to 78 000 in 2017. And in London alone there are an estimated 225 000 “hidden homeless” people aged 16-25—arranging their own temporary accommodation with friends or family. This rise in homelessness is not confined to the England but has affected most European countries.
AORTIC STENOSIS AND FUNCTIONAL MITRAL REGURGITATION: UNDERSTANDING THE RELATIONSHIP BETWEEN MORPHOLOGY AND FUNCTION ACCORDING TO LEFT VENTRICULAR CONCENTRICITY AND DILATATION
Authors: Stephanie Kochav, Jonathan Kochav, Nicholas Ngiam, Edgar Tay, Tiong Cheng Yeo, Kian Keong Poh
Journal: Journal of the American College of Cardiology (2018)
Long‐term outcomes of endoscopic submucosal dissection for high‐grade dysplasia and early‐stage carcinoma in the colorectum
Authors: Tao Chen, Wen‐Zheng Qin, Li‐Qing Yao, Yun‐Shi Zhong, Yi‐Qun Zhang, Wei‐Feng Chen, Jian‐Wei Hu, Marie Ooi, Ling‐Li Chen, Ying‐Yong Hou, Mei‐Dong Xu, Ping‐Hong Zhou
Journal: Cancer Communications (2018)

Colorectal carcinomas (CRCs) arise from premalignant precursors in an adenoma-carcinoma sequence, in which adenoma with high-grade dysplasia (HGD) and early-stage carcinoma are defined as advanced neoplasia. A limited number of studies have evaluated the long-term outcomes of endoscopic submucosal dissection (ESD) for advanced colorectal neoplasia. This study aimed to assess the efficacy and safety of ESD for advanced colorectal neoplasia as well as the long-term outcomes, including local recurrence and metastasis.We analyzed data collected from 610 consecutive patients with 616 advanced colorectal neoplasia lesions treated with ESD between January 2007 and December 2013. Clinical, endoscopic, and histological data were collected over a median follow-up period of 58 months to determine tumor stage and type, resection status, complications, tumor recurrence, and distant metastasis.The overall rates of en bloc resection, histological complete resection, and major complications were 94.3%, 89.4%, and 2.3%, respectively. Hybrid ESD was an independent factor of piecemeal resection. Tumor location in the colon was associated with increased risk of ESD-related complications. During the follow-up period, all patients remained free of metastasis. However, local recurrence occurred in 4 patients (0.8%); piecemeal resection was a risk factor.ESD is effective and safe for resection of advanced colorectal neoplasia, with a high en bloc resection rate and favorable long-term outcomes. ESD is indicated for the treatment of HGD and early-stage CRC to obtain curative resection and reduce local recurrence rate.
Abstract OT2-01-05: Sentinel lymphnode biopsy (SLNB) and targeted axillary surgery (TAS) by indocyaningreen (ICG) and a novel near-infrared color camera system - a prospectively randomised, multicenter study to avoid radioactivity in a time-/cost-saving procedure in primary breast cancer
Authors: P Kern, R Kimmig, M Rezai, O Hoffmann, I Bücker, M Braun
Journal: Cancer Research (2018)

Abstract Background: Sentinel lymph node biopsy (SLNB) by radioactively labelled 99mTechnetium +/- patent blue is so far the current standard in SLN detection. However, it remains a time- and cost-consuming procedure requiring the availability of a nuclear medicine department and a precise coordination with the subsequent surgery. It could be desirable to empower surgeons to be independent from availability of a nuclear source and to spare patients from radioactivity. Indocyanine green (ICG) as a fluorescent coloring agent is already known as safe in diagnostics for heart, circulation, liver and eye disease and may represent a valid alternative to 99mTc and patent blue (PBD), especially as it does not cause aesthetic impairment of the breast, with ICG being only visible with near infra-red light. Methods: This prospective, randomized study is a non-inferiority trial to evaluate ICG-fluorescence as an alternative to either 99mTc and/or patent blue dye for sentinel lymph node detection of primary breast cancer with and without neoadjuvant chemotherapy. Patients, aged 18 - 80 years, with unilateral or bilateral, unifocal or multifocal/ multicentric primary breast cancer without signs of metastases and written consent are eligible for this study. ECOG status of 0-2 and life expectancy &amp;gt; 1 year is required. All BMI classes are admitted to the study, with predefined subgroups of a) &amp;lt;= 20 b) &amp;gt;20-30 c) &amp;gt;30-40 d) &amp;gt;40. Tumor stages included are a) Tis (&amp;gt;= 4 cm) b) T1 c) T2 and d) T3. ICG-guided SLNB may be applied in patients in the following settings: a) before neoadjuvant, b) after neoadjuvant chemotherapy. Primary Endpoints: Rate of SLN detection by either of the methods in the following 3 arms of the trial: Arm A: 99mTc + patent blue dye (PBD) Arm B: 99mTc + indocyanine green (ICG) Arm C: Indocyanine green (ICG) Secondary Endpoints: - Time to identify (TTI) sentinel lymph node(s) (min) - Number of sentinel lymph nodes (SLN) and non-sentinel lymph nodes (non-SLN) - Rate of concordance of detection by 99mTc+patent blue dye (PBD) vs. 99mTc + ICG - Dose of radioactivity omitted in Arm C vs. Arm A &amp; B Results: This trial is in progress. Citation Format: Kern P, Kimmig R, Rezai M, Hoffmann O, Bücker I, Braun M. Sentinel lymphnode biopsy (SLNB) and targeted axillary surgery (TAS) by indocyaningreen (ICG) and a novel near-infrared color camera system - a prospectively randomised, multicenter study to avoid radioactivity in a time-/cost-saving procedure in primary breast cancer [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 OT2-01-05.
AJMER ULNAR ANGIOPLASTY STUDY (AJULAST) STUDY: ULNAR ACCESS IS NON INFERIOR TO RADIAL ACCESS ANGIOPLASTY
Authors: Rajendra Kumar Gokhroo, Kailash Chandra, Shashi Kant Pandey, Ramsagar Roy, Rajesh Nandal
Journal: Journal of the American College of Cardiology (2018)
Abstract OT1-04-02: Mifepristone treatment for breast cancer patients expressing levels of progesterone receptor isoform A (PRA) higher than those of isoform B (PRB)
Authors: M Liguori, C Lanari, H Gass, P Rojas, A Elia, P Martinez Vazquez, J Burruchaga, P Gonzalez, I Caillet Bois, C Ventura, G San Martin, A Castets, S Lovisi, G Acosta Haab, C Lamb, V Fabris, V Novaro, A Molinolo
Journal: Cancer Research (2018)

Abstract Seventy percent of breast cancers express estrogen (ER) and progesterone receptors (PR) and respond to antiestrogen therapies. Emerging evidence from experimental studies and human epidemiology, points to a relevant role for progestins in breast carcinogenesis and cancer growth. Others and we have proposed that there is a role for antiprogestins in the therapeutic armamentarium, but the challenge remains to identify which patients would benefit from targeting the PR in addition to ER. Preclinical data indicates that antiprogestins block cell proliferation and increase apoptosis only in ER+ breast cancers expressing levels of PRA higher than those of PRB. The aim of this study is to evaluate the therapeutic effects of Mifepristone (MFP) on breast cancer patients selected by their PRA/PRB isoform ratio, for 14 days in between core biopsy and surgery (MIPRA trial ClinicalTrials.gov Identifier: NCT02651844). Methods: This is an open label, interventional with single group assignment study. We perform core biopsies on menopausal patients with clinically palpable breast cancers larger than 1.5 cm to confirm diagnosis. We will assess the PRA/PRB ratio by western blotting in frozen samples and total PR in formalin-fixed samples by immunohistochemistry (IHC). Twenty eligible PR+ patients (PR &amp;gt; 50 %) with PRA/PRB ≥1.5 who have signed consent forms, and meet the inclusion criteria will be recruited. Patients will be treated for 14 days with MFP p.o 200 mg. Surgery will be performed on day 15. Samples will be frozen for molecular studies or fixed for IHC. The primary outcome is the evaluation of Ki-67 staining pre- and post treatment. Secondary outcomes include comparatively expression of proliferation/apoptosis/PR signaling markers in core and surgical biopsy samples. Other pre-specified outcomes include molecular profiling, study of liquid biopsies, mammography, and ultrasound studies. Wilcoxon signed rank test will be used to evaluate differences in biomarker expression between core biopsy and surgical samples of each patient. Citation Format: Liguori M, Lanari C, Gass H, Rojas P, Elia A, Martinez Vazquez P, Burruchaga J, Gonzalez P, Caillet Bois I, Ventura C, San Martin G, Castets A, Lovisi S, Acosta Haab G, Lamb C, Fabris V, Novaro V, Molinolo A. Mifepristone treatment for breast cancer patients expressing levels of progesterone receptor isoform A (PRA) higher than those of isoform B (PRB) [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 OT1-04-02.
Ethnicity, obesity and the prevalence of impaired glucose tolerance and type 2 diabetes in PCOS: a systematic review and meta-regression
Authors: N S Kakoly, M B Khomami, A E Joham, S D Cooray, M L Misso, R J Norman, C L Harrison, S Ranasinha, H J Teede, L J Moran
Journal: Human Reproduction Update (2018)

Our prior meta-analyses demonstrated an increased prevalence of impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) with polycystic ovary syndrome (PCOS), but with substantial clinical heterogeneity.We aimed to update our previous review to quantify the prevalence of IGT and T2DM in PCOS with only quality studies (good and fair quality). We also aimed to examine the contribution of parameters including ethnicity, obesity and method of diagnosing T2DM in explaining the observed heterogeneity in IGT and T2DM prevalence in PCOS.We conducted a literature search (MEDLINE, CINAHL, EMBASE, clinical trial registries and hand-searching) up to June 2016 to identify studies reporting the prevalence of dysglycemia (IGT and T2DM) in women with and without PCOS. We included studies where women with PCOS (defined according to original National Institute of Health) were compared to women without PCOS for the end-points of the prevalence of IGT or T2DM. We excluded case reports, case series, editorials, and narrative reviews. Studies where PCOS was diagnosed by self-report, or where IGT or T2DM were measured by fasting glucose, only were excluded. We assessed the methodological quality of the included studies using a priori criteria based on the Newcastle-Ottawa Scaling (NOS) for non-randomized studies. Data are presented as odds ratio (OR) (95% CI) with random-effects meta-analysis by Mantel-Haenszel methods. We assessed the contribution of demographic and clinical factors to heterogeneity using subgroup and meta-regression analysis.We reviewed 4530 studies and included 40 eligible studies in the final analysis. On meta-analysis of quality studies, women with PCOS had an increased prevalence of IGT (OR = 3.26, 95% CI: 2.17-4.90) and T2DM (OR = 2.87, 95% CI: 1.44-5.72), which differed by ethnicity (for IGT, Asia: 5-fold, the Americas: 4-fold and Europe: 3-fold), was higher with obesity, and doubled among studies using self-report or administrative data for diagnosing diabetes. The ethnicity-related difference retained its significance for Asia and Europe in BMI-matched subgroups. Clear contributors to heterogeneity did not emerge in meta-regression.Our findings underscore the importance of PCOS as a cause of dysglycemia with a higher prevalence of IGT and T2DM. They support the relevance of ethnicity and obesity and emphasize the need for accurate diagnostic methods for diabetes.CRD42017056524.
ENVIRONMENT-WIDE ASSOCIATION STUDY TO IDENTIFY NOVEL FACTORS ASSOCIATED WITH PERIPHERAL ARTERIAL DISEASE: EVIDENCE FROM THE NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEY (1999-2004)
Authors: Xiaodong Zhuang, Lizhen Liao, Ao Ni, Daya Yang, Yue Guo, Xueqin Wang, Xinxue Liao
Journal: Journal of the American College of Cardiology (2018)
Clinical outcomes of gastric cardia cancer during a recent decade of Korea.
Authors: Sung Woo KO
Journal: Journal of Clinical Oncology (2018)

87 Background: To date, the incidence of adenocarcinomas of the gastric cardia has been increasing worldwidely. In 7 th edition of the American Joint Commission on Cancer, a tumor within 5 cm of the EGJ is classified and staged according to the esophageal cancer. There are two different etiologies of gastric cardia cancer - Barrett's esophagus and Helicobacter pylori (H. pylori) associated intestinal metaplasia. We aimed to evaluate the clinical characteristics and outcome between gastric cardia and non-cardia cancer. Methods: We performed a retrospective cohort study of 90 patients with gastric cardia cancer from Jan. 2003 to Dec. 2013. We selected 180 patients with gastric non-cardia cancer as age and sex matched control during the same period (by AGE, SEX PROGRAM). Results: The rate of curative resection (R0) was significantly low in gastric cardia cancer (74/81 vs. 146/149) (91.4% vs 98.0%, P=.02) The recurrence rate was lower in patents with non-cardia cancer than those with cardia cancer (21/74 vs. 12/146) (28.4% vs 8.0%, P=.00). Subgroup analysis was done for patients with cardia cancer according to BMI and helicobacter infection and atrophic mucosal change. The median follow up period of obese patients and non-obese patients were 35.0month and 28.0month, which revealed there was no difference (P=.70). We determined patients with mucosal atrophic change and HP infection as a group1, and patients with no mucosal change with non- infective status as a group 2. The median follow up period of group 1 patient and group 2 patients were 26.0month and 36.0month, there was no significant difference. (P=.96). Conclusions: Gastric cardia cancer had a negative prognostic impact, compared with gastric non-cardia cancer. Although a possible heterogeneity in the pathogenesis and biological behavior of gastric cardia cancer would be present, there was no difference in prognosis.
Road traffic injuries in shared bicycle riders in China
Authors: Chuanxi Fu, Qing Guo
Journal: The Lancet Public Health (2018)

The internet-based bicycle sharing systems, widely implemented in China in late 2016, has proved effective in filling the so-called last mile traffic gap for city commuters. By July 2017, it was estimated that 16 million shared bicycles had been launched in China, with 106 million users.1 In November 2017, we surveyed 2883 shared bicycle riders. On average, each respondent spent 43·9 min riding shared bicycles during the week before the survey.
Diploma in clinical education
Authors: Jane H Roberts
Journal: BMJ (2005)

For doctors actively involved in teaching either at undergraduate or postgraduate level. You must have completed the certificate in clinical education to register (soon to open to non-clinicians).⇓



In 2002-4, at the start of my career in academic medicine.

I needed to become quickly familiar with educational theory within a medical context, in order to contribute effectively to curriculum development in my job. The course also offered the chance to focus on my specific areas of interest.

You need to …
P037 Multiple roles of phospholipase C-ETA2, as a novel C2 domain containing protein, in the pathogenesis of rheumatoid arthritis
Authors: SI Lee, JH Park, HS Noh, W-U Kim
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> The <i>C2 domain</i> is a Ca<sup>2+</sup>-dependent membrane-targeting motif found in many cellular proteins involved in signal transduction or inflammation pathway. However, the effects of C2 domain-containing proteins in the fibroblast-like synoviocyte (FLS) of rheumatoid arthritis (RA) have not yet been elucidated. <h3>Objectives</h3> The aim of this study was to screen novel C2 domain-containing proteins related to aggressiveness of FLS, and confirm the precise roles of target protein in RA. <h3>Methods</h3> We transduced RA-FLS with a recombinant adenovirus expressing a C2 domain library. To confirm the effect of phospholipase C-eta2 (PLCH2), as a candidate C2 domain-containing target protein, we established stable MH7A cell lines overexpressing GFP-tagged PLCH2. We also conducted <i>in vitro</i> and <i>in vivo</i> experiments using a recombinant adenovirus expressing the full length form of PLCH2 or C2 domain of PLCH2 (C2-PLCH2). <h3>Results</h3> Several C2 domain-containing proteins were identified whose over-expression resulted in reduced proliferation and NF-kB activity of RA-FLS. Among those, we focused on PLCH2 in this study. PLCH2 levels were significantly decreased in RA-FLS and synovium than OA. PLCH2 and C2-PLCH2 suppressed cell invasion and migration, cytokines production, and matrix metalloproteinase secretion in RA-FLS and stable MH7A cell lines compared to control. PLCH2 and C2-PLCH2 sensitised RA-FLS to apoptosis <i>in vitro</i> and <i>in vivo</i> model of matrigel implants engrafted into immunodeficient mice. PLCH2 and C2-PLCH2 further decreased arthritis severity in collagen-induced arthritis (CIA) mouse model. <h3>Conclusions</h3> Our results showed that invasive characteristics of RA-FLS and inflammatory arthritis of CIA are reduced by PLCH2 and C2 domain of PLCH2. Therefore C2 domain of PLCH2 may have therapeutic potential for RA. <h3>References</h3> . Farah CA, Sossin WS. The role of C2 domains in PKC signalling. Adv Exp Med Biol2012;740:663–83. . Yáñez M, Gil-Longo J, Campos-Toimil M. Calcium binding proteins. Adv Exp Med Biol2012;740:461–82. . Friedrich R, Yeheskel A, Ashery U. DOC2B, C2 domains, and calcium: A tale of intricate interactions. Mol Neurobiol2010February;41(1):42–51. . Zhou Y, Sondek J, Harden TK. Activation of human phospholipase C-eta2 by Gbetagamma. Biochemistry2008April 15;47(15):4410–7. . Popovics P, Beswick W, Guild SB, Cramb G, Morgan K, Millar RP, Stewart AJ. Phospholipase C-η2 is activated by elevated intracellular Ca(2+) levels. Cell Signal2011November;23(11):1777–84. <h3>Acknowledgements</h3> This work was supported by grants (NRF-2014R1A2A1A11051360 and NRF-2015R1A5A2008833) from the National Research Foundation of Korea (NRF) funded by the Korean government (MSIP). <h3>Disclosure of interest</h3> None declared
Allowing different providers to compete for primary care services is good news for GPs
Authors: Chris Johnstone
Journal: BMJ (2006)

AGAINST 



The NHS is astonishing. It provides a high level of care to a whole population based on need and not want. It is free to all at the point of contact. It is remarkably cost efficient, despite what the government and private healthcare groups would lead you to believe. Even the oft quoted article comparing Kaiser Permanente with the NHS found that the NHS was better, and its contrary conclusions have been comprehensively repudiated.

It is commonly accepted that countries with effective healthcare systems have a high primary care index, and the United Kingdom has one of the highest in the world. GPs …