tbuckley/cabot-search huggingface dataset:
Doctors returning to practice after an absence of three months or more should undergo retraining
Authors: Helen Jaques
Journal: BMJ (2012)

Doctors who have been away from clinical practice for three months or more should be assessed and undergo retraining before returning to practice, the Academy of Medical Royal Colleges has recommended.

The academy has published guidance on measures to support doctors returning to the same area of clinical practice as previously practised after a period of absence, such as for …
Hepatic arterial infusion of oxaliplatin plus fluorouracil/leucovorin vs. sorafenib for advanced hepatocellular carcinoma
Authors: Ning Lyu, Yanan Kong, Luwen Mu, Youen Lin, Jibin Li, Yaru Liu, Zhenfeng Zhang, Lie Zheng, Haijing Deng, Shaolong Li, Qiankun Xie, Rongping Guo, Ming Shi, Li Xu, Xiuyu Cai, Peihong Wu, Ming Zhao
Journal: Journal of Hepatology (2018)
Pathways Impacted by Genomic Alterations in Pulmonary Carcinoid Tumors
Authors: Michael K. Asiedu, Charles F. Thomas, Jie Dong, Sandra C. Schulte, Prasidda Khadka, Zhifu Sun, Farhad Kosari, Jin Jen, Julian Molina, George Vasmatzis, Ray Kuang, Marie Christine Aubry, Ping Yang, Dennis A. Wigle
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Pulmonary carcinoid tumors account for up to 5% of all lung malignancies in adults, comprise 30% of all carcinoid malignancies, and are defined histologically as typical carcinoid (TC) and atypical carcinoid (AC) tumors. The role of specific genomic alterations in the pathogenesis of pulmonary carcinoid tumors remains poorly understood. We sought to identify genomic alterations and pathways that are deregulated in these tumors to find novel therapeutic targets for pulmonary carcinoid tumors. Experimental Design: We performed integrated genomic analysis of carcinoid tumors comprising whole genome and exome sequencing, mRNA expression profiling and SNP genotyping of specimens from normal lung, TC and AC, and small cell lung carcinoma (SCLC) to fully represent the lung neuroendocrine tumor spectrum. Results: Analysis of sequencing data found recurrent mutations in cancer genes including ATP1A2, CNNM1, MACF1, RAB38, NF1, RAD51C, TAF1L, EPHB2, POLR3B, and AGFG1. The mutated genes are involved in biological processes including cellular metabolism, cell division cycle, cell death, apoptosis, and immune regulation. The top most significantly mutated genes were TMEM41B, DEFB127, WDYHV1, and TBPL1. Pathway analysis of significantly mutated and cancer driver genes implicated MAPK/ERK and amyloid beta precursor protein (APP) pathways whereas analysis of CNV and gene expression data suggested deregulation of the NF-κB and MAPK/ERK pathways. The mutation signature was predominantly C&amp;gt;T and T&amp;gt;C transitions with a minor contribution of T&amp;gt;G transversions. Conclusions: This study identified mutated genes affecting cancer relevant pathways and biological processes that could provide opportunities for developing targeted therapies for pulmonary carcinoid tumors. Clin Cancer Res; 24(7); 1691–704. ©2018 AACR.
Nomogram-based risk prediction of local and distant relapse after radical cystectomy, and role of perioperative chemotherapy, in patients with muscle-invasive bladder cancer (MIBC): A multicenter study.
Authors: Andrea Necchi, Gregory Russell Pond, Elizabeth R. Plimack, Guenter Niegisch, Evan Y. Yu, Sumanta K. Pal, Aristotelis Bamias, Neeraj Agarwal, Ajjai Shivaram Alva, Sandy Srinivas, Simon J. Crabb, Ulka N. Vaishampayan, Daniel W. Bowles, Dominik R. Berthold, Christine Theodore, Srikala S. Sridhar, Thomas Powles, Jonathan E. Rosenberg, Joaquim Bellmunt, Matt D. Galsky
Journal: Journal of Clinical Oncology (2018)

448 Background: Neoadjuvant and adjuvant chemotherapy improve relapse-free survival (RFS) and overall survival of patients (pts) with MIBC. Limited information is available regarding risk prediction of local (R L ) vs. distant relapse (R D ), including role of perioperative chemotherapy (POC), added to radical cystectomy (Cy). Methods: Data from 1,559 pts, treated at 29 centers from the U.S., Europe, Israel, and Canada, were collected. Pts received Cy for MIBC from 02/90 to 12/13. Of these pts, 782 (50.2%) received POC and Cy, 777 (49.8%) Cy alone. R L and R D were defined as follows: pelvic lymph-nodes/soft tissue only and any extra-pelvic recurrences, respectively. Cumulative incidence methods were used to estimate time-to-(TT) R L /R D , which accounts for the competing risk of other types of relapse. Univariable and multivariable (MVA) Cox regression analyses were performed from the complete-case dataset (n = 1,082). Risk groups were defined according to the number of adverse factors, with corresponding nomogram-based R L and R D risk estimation. All tests were two-sided and statistical significance was defined as a p-value of 0.05 or less. Results: A total of 830 pts (55%) developed a relapse, 447 in the Cy group and 383 in the Cy+POC group. On MVA, POC administration was associated with longer TTR L (p &lt; 0.001) and TTR D (p &lt; 0.001). Other factors associated with R L : histology (non-UC, odds ratio [OR] = 1.47, 95%CI: 1.07-2.01, p = 0.022), pT-stage (p &lt; 0.001), pN-stage (p = 0.038), surgical margins (p &lt; 0.001). For R D : Charlson score (p = 0.006), pT-stage (p &lt; 0.001), pN-stage (p &lt; 0.001). The c-index of the model for R L was 0.685 (95% bootstrapped CI: 0.664-0.718), and for R D was 0.684 (0.655-0.721). Three risk group categories were obtained for both endpoints (0, 1-2, and &gt; 2 risk factors). Results were confirmed after applying 90-day or 180-day landmark analyses, pending external validation. Conclusions: In the largest study that separately analyzed R L and R D risk, we were able to provide risk tools that may be used to optimize locoregional treatments and compare POC benchmark with new drugs in the perioperative setting.
CONFIRMATIVE PHASE III GLOBAL CLINICAL TRIAL OF A BOTANICAL DRUG IN PATIENTS WITH CHRONIC STABLE ANGINA (CAESA): NEW TREATMENT OPTIONS FOR MYOCARDIAL ISCHEMIA HEART DISEASE
Authors: Henry Sun, Zhixin Guo, Lingyan Li, Naifeng Wu, Kaijing Yan, Xijun Yan
Journal: Journal of the American College of Cardiology (2018)
MYOCARDIAL INFARCTION WITH NON-OBSTRUCTIVE CORONARY ARTERIES (MINOCA) ACCORDING TO DEFINITIONS OF 2016 ESC POSITION PAPER: CLINICAL PROFILE AND PROGNOSIS
Authors: Barbara Izquierdo Coronel, Javier Lopez Pais, David Galan Gil, Maria Jesus Espinosa Pascual, Paula Awamleh, Carlos Gustavo Martínez Peredo, Alfonso Fraile Sanz, Javier Ceballo, Joaquin Alonso Martin
Journal: Journal of the American College of Cardiology (2018)
Abstract 19341: The Role of Mul1, a Mitochondrial Localized E3 Ligase, in the Heart
Authors: Yanfei Yang, Madyson Noonan, Lucia Cilenti, Yiling Qiu, Antonis Zervos, Ronglih Liao
Journal: Circulation (2016)

Background:  Mitochondrial (Mito) quality is a key determinant of cardiac health and pathology. Mito quality control is maintained in part through fusion and fission of the Mito network and removal of damaged organelles through mitophagy. However, the molecular underpinnings of maintaining a healthy intracellular Mito pool are unclear. A Mito localized ubiquitin/SUMO E3 ligase, Mul1, has been suggested as a critical regulator of Mito quality control; however, the role of Mul1 in the heart, a Mito-dependent organ, has not yet been characterized.   Methods:  We used adenovirus-mediated delivery of Mul1 overexpression (Adv-Mul1) and short hairpin RNA Mul1 knockdown (Adv-ShMul1) to neonatal rat ventricular cardiomyocytes (CMs) and assessed Mito morphology, function and overall cell survival.   Results:  Adv-Mul1 localized to the outer Mito membrane, similar to endogenous Mul1. Adv-Mul1 dramatically altered Mito morphology from tubular to punctate, as well as reduced Mito membrane potential (ΔΨm). Electron microscopy demonstrated that Adv-Mul1 induced cristae remodeling, which may explain the loss of respiratory function analyzed by the Seahorse system. In addition, Adv- Mul1 increased mitochondrial calcium levels and cytochrome c release, resulting in increased cell death. Importantly, Mul1 knockdown using Adv-ShMul1 rescued CCCP-induced reduction in Mito ΔΨm, suggesting Mul1 critically regulates Mito quality control in CMs. Adv- Mul1 results in degradation of Mfn2 and Drp1, key regulators of Mito dynamics. In Adv-Mul1 CMs, adenovirus-mediated normalization of Drp1 levels restored Mito ΔΨm and cell death, but not Mito fragmentation, suggesting a requirement of both Mfn2 and Drp1 proteins. To determine if Mul1 functions in part through its post-translational modification of substrates via RING domain, we constructed a RING domain truncated Mul1, which was unable to alter the Mito respiration or induce cell death. This data suggests that Mul1 mediated Mito structural and functional alterations are dependent on its RING domain.   Conclusion:  Mul1 induces Mito dysfunction and cell death in CMs, which is mediated by its RING domain and downregulation of Drp1. Thus, our work helps characterize a novel regulator of Mito quality control in the heart.
USE OF DUAL-ENERGY CORONARY COMPUTED TOMOGRAPHY FOR EVALUATION OF NECROTIC CORE IN PATIENTS WITH SUDDEN CARDIAC DEATH
Authors: Aeshita Dwivedi, Fay Lin, Navneet Narula, Asim Rizvi, Wijnand Stuijfzand, Ji Hyun Lee, Donghee Han, Yao Lu, Mahn Won Park, Hadi Mirhedayati Roudsari, Alessandra DiFranco, Kazuyuki Yahagi, Sho Torii, Robert Kutys, Erica Jones, Jessica Pena, Subhi Al’Aref, Michael Eagle, Dana Jackson, David Fowler, James Earls, James K. Min, Renu Virmani
Journal: Journal of the American College of Cardiology (2018)
1,25-Dihydroxyvitamin D3 protects obese rats from metabolic syndrome via promoting regulatory T cell-mediated resolution of inflammation
Authors: Wen Jin, Bing Cui, Pingping Li, Fang Hua, Xiaoxi Lv, Jichao Zhou, Zhuowei Hu, Xiaowei Zhang
Journal: Acta Pharmaceutica Sinica B (2018)

Vitamin D3 has been found to produce therapeutic effects on obesity-associated insulin resistance and dyslipidemia through its potent anti-inflammatory activity, but the precise immunomodulatory mechanism remains poorly understood. In the present study we found that 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], the biologically active form of vitamin D3, significantly attenuated monosodium glutamate (MSG)-induced obesity and insulin resistance as indicated by body weight reduction, oral glucose tolerance improvement, and a glucose infusion rate increase as detected with hyperinsulinemic-euglycemic clamp. Moreover, 1,25(OH)2D3 not only restored pancreatic islet functions but also improved lipid metabolism in insulin-targeted tissues. The protective effects of 1,25(OH)2D3 on glycolipid metabolism were attributed to its ability to inhibit an obesity-activated inflammatory response in insulin secretory and targeted tissues, as indicated by reduced infiltration of macrophages in pancreas islets and adipose tissue while enhancing the expression of Tgf-β1 in liver tissue, which was accompanied by increased infiltration of Treg cells in immune organs such as spleen and lymph node as well as in insulin-targeted tissues such as liver, adipose, and muscle. Together, our findings suggest that 1,25(OH)2D3 serves as a beneficial immunomodulator for the prevention and treatment of obesity or metabolic syndrome through its anti-inflammatory effects.
Positron emission tomography/computed tomography with 18F-fluorocholine improve tumor staging and treatment allocation in patients with hepatocellular carcinoma
Authors: Julia Chalaye, Charlotte E. Costentin, Alain Luciani, Giuliana Amaddeo, Nathalie Ganne-Carrié, Laurence Baranes, Manon Allaire, Julien Calderaro, Daniel Azoulay, Pierre Nahon, Olivier Seror, Ariane Mallat, Michael Soussan, Christophe Duvoux, Emmanuel Itti, Jean Charles Nault
Journal: Journal of Hepatology (2018)
Are there any opportunities for working for an out of hours provider by doing telephone triage at a distance—that is, from Bangladesh? The hours would work; I am experienced in general practice and out of hours work, including telephone triage; and it could provide some useful income while we live there doing some voluntary work.
Authors: Rodger Charlton
Journal: BMJ (2005)

<b>www.bmjcareers.com/advicezone</b> Have a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone 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.
Using verbal autopsies to estimate under-5 mortality at household level in a rural area of southwestern Uganda: a cross-sectional study
Authors: Doreen Nabukalu, Moses Ntaro, Mathias Seviiri, Radhika Sundararajan, Raquel Reyes, Ross Boyce, Edgar Mulogo
Journal: The Lancet Global Health (2018)

BackgroundIn rural Uganda, paediatric deaths that occur outside of health facilities often go unnoticed by the health system, and information on their magnitude and causes remains limited. We aimed to assess the causes of mortality of children younger than 5 years at household level in Bugoye subcounty, Uganda.MethodsThis cross-sectional study was done in all 35 villages of Bugoye subcounty in March and April, 2017. Community health workers collected data on all deaths in all households of the subcounty that occurred between Jan 1, 2016, and Jan 1, 2017, using 2014 WHO standardised verbal autopsy (VA) questionnaires. Causes of death were determined using the InterVA-4 algorithm and cause-specific mortality proportions were calculated using STATA.FindingsThe VA survey identified 77 deaths among children younger than 5 years that occurred during the study period. Nearly half of these deaths occurred among neonates (n=38 [49%]), followed by ages 1–11 months (n=21 [27%]), and 1–4 years (n=18 [23%]). Among neonates, mortality most commonly occurred in the first 24 h (n=17 [22%]), followed by 8–28 days (n=10 [13%]). The five leading causes of death for all ages were malaria (19%), prematurity (19%), neonatal pneumonia (16%), HIV/AIDS-related illnesses (10%), and acute respiratory tract infections including pneumonia (9%). Malaria was the dominant cause of death for those aged 1–11 months and 1–4 years, accounting for 44% and 33%, respectively. Prematurity and neonatal pneumonia were the leading causes of death among neonates. Most deaths (81%) captured from the VAs could not be traced from the records of the reported health facilities in the district.InterpretationThere is a considerable discrepancy between mortality captured by the district and mortality in the communities. Interventions that address common causes of mortality for children younger than 5 years need to be strengthened and extended to rural health facilities. Community death registration systems are lacking and in need of revitalisation. VA surveys could be conducted by district health authorities periodically to collect mortality data in the rural and hard-to-reach areas.FundingJoint AFRO/TDR Small Grants Scheme for implementation research in infectious diseases of poverty.
Reduced Secondhand Smoke Exposure After Implementation of a Comprehensive Statewide Smoking Ban—New York, June 26, 2003–June 30, 2004
Authors: J Hadler, M Fraser, P Martell-Cleary, M Farley, C Morin, B Jewell, L Triden, J Bareta, K Angeles, J Keefe, K Johnson, L Butler, New Mexico, N Spina, G Smith, B Anderson, W Schaffner
Journal: JAMA (2007)
P1.10-008 Palliative Care and Hospice Resources are Underutilized in Patients with Advanced Non-Small Cell Lung Cancer
Authors: J. Rayburn, C. Wilshire, C. Gilbert, B. Louie, R. Aye, A. Farivar, E. Vallieres, J. Gorden
Journal: Journal of Thoracic Oncology (2017)
ASSOCIATIONS OF SLEEP DURATION, INSOMNIA AND FREQUENT NOCTURNAL AWAKENING WITH ATRIAL FIBRILLATION: A META-ANALYSIS
Authors: Ronpichai Chokesuwattanaskul, Charat Thongprayoon, Soontharee Congrete, Tanyanan Tanawuttiwat, Somchai Prechawat, Voravut Rungpradubvong
Journal: Journal of the American College of Cardiology (2018)
I worked in anaesthetics for 12 months and finished in May 2005. Unfortunately I was referred to “Doctors with Difficulties”; the deanery could not help me. The royal college has agreed to give me an extension for another six months of my limited registration and has asked me to secure an SHO post (training position only) as early as possible. Any advice?
Authors: Leyla Sanai
Journal: BMJ (2006)

Have a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone 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. <b>www.bmjcareers.com/advicezone</b>
Gray's Anatomy for Students
Authors: Mohammad Heetun
Journal: BMJ (2006)

Richard L Drake, Wayne Vogl, and Adam WM Mitchell

Elsevier Churchill Livingstone, 2005, £39.99, 1058 pages

ISBN: 0 443 06612 4

Rating: ★★★★/5



Anatomy can be a difficult subject to study from a book. For it to be truly understood, it needs to be studied alongside dissected specimens or seen clinically in order to gain a proper appreciation of the orientation and three dimensional nature of structures. With increasing constraints on today's medical curriculum, however, there is less time for the medical student to dissect or view specimens, and the unfortunate reality is that for many doctors, anatomy will be learnt predominantly from a textbook

Now as an anatomy …
ASSOCIATION BETWEEN PLASMA ANNEXINS &amp; VASCULAR FUNCTION IN AFRICAN AMERICAN DIABETIC PATIENTS
Authors: Ajibola M. Adedayo, Ayobami Eluwole, Fasika Tedla, Arye Kremer, Nicole Mastrogiovanni, Muhammad Khan, Carl Rosenberg, Paul Dreizen, John LaRosa, Louis Salciccioli, Mohamed Boutjdir, MaryAnn Banerji, Clinton Brown, Moro Salifu, Jason Lazar, Ahmed Bakillah
Journal: Journal of the American College of Cardiology (2018)
Abstract P1-17-08: Efficacy of lapatinib and capecitabine combination therapy in brain metastases from HER-2 positive metastatic breast cancer: A systematic review and meta- analysis
Authors: KZ Thein, MH Zaw, R Yendala, HP Igid, C Chai-Adisaksopha, F Hardwicke, S Awasthi, S Radhi
Journal: Cancer Research (2018)

Abstract Background: Brain metastases contribute to significant morbidity and mortality in breast cancer. Approximately one fourth of breast tumors overexpress the human epidermal growth factor receptor 2 (HER2) protein and are twice as likely to develop brain metastases. There are currently no systemic therapies approved. We undertook a systematic review and pooled analysis of trials to determine the efficacy of lapatinib and capecitabine combination therapy in brain metastases from HER-2 positive metastatic breast cancer (MBC). Methods: We performed a comprehensive literature search using MEDLINE, EMBASE databases, and meeting abstracts through December 31, 2016. Trials that utilized lapatinib and capecitabine combination therapy in brain metastases from HER-2 positive MBC were incorporated in the analysis. The pooled estimated rates were calculated using random effects model. Heterogeneity was assessed using I2 statistic. Results: A total of 513 patients with brain metastases from HER-2 positive MBC from 6 trials and a subgroup of another 4 trials were included in our analysis. Lapatinib and capecitabine therapy was used as second-line treatment in 9 studies (n= 468) and as first-line treatment in the LANDSCAPE study (n= 45). Three studies were retrospective evaluations of randomized trials and the rest were phase 2 trials. CNS objective response rate (ORR) was 26% (95% CI: 19 – 33, I2: 65.9%). Complete response (CR) rate was 1% (95% CI: 0 - 2, I2: 0.0%) and partial response (PR) rate was noted at 24% (95% CI: 17- 31, I2: 66.1%). Stable disease (SD) occurred in 37% (95% CI: 29- 45, I2: 66.6%) and progressive disease (PD) in 19% (95% CI: 12- 25, I2: 66.5%). The first line LANDSCAPE study had the highest PR (49%) and ORR (53%) without a significant impact on CR rate; PD was 7%. Conclusion: Brain metastases in breast cancer is an area of urgent unmet need. Our meta-analysis showed that lapatinib/capecitabine therapy had some first line or second line activity in brain metastases from HER-2 positive MBC. Nevertheless, further randomized controlled trials are required in this patient population. Citation Format: Thein KZ, Zaw MH, Yendala R, Igid HP, Chai-Adisaksopha C, Hardwicke F, Awasthi S, Radhi S. Efficacy of lapatinib and capecitabine combination therapy in brain metastases from HER-2 positive metastatic breast cancer: A systematic review and meta- analysis [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 P1-17-08.
Increased Circulating Follicular Treg Cells Are Associated With Lower Levels of Autoantibodies in Patients With Rheumatoid Arthritis in Stable Remission
Authors: Chen Liu, Dongwei Wang, Songsong Lu, Qinzhu Xu, Lei Zhao, Jingzhong Zhao, Ying Song, Hui Wang
Journal: Arthritis & Rheumatology (2018)

Objective To examine the expression and changes in function of circulating CD 4+ CXCR 5+FoxP3+ follicular Treg (Tfr) cells in patients with active rheumatoid arthritis ( RA ) and in patients with RA in stable remission, and to clarify the role of Tfr cells in the pathogenesis of RA . Methods Levels of Tfr cells and follicular helper T (Tfh) cells in the peripheral blood of 39 patients with active RA , 39 patients with RA in stable remission, and 33 healthy controls were detected by flow cytometry. The function of Tfr cells was measured by coculturing them with Tfh cells and B cells. Activated CD 45 RA −FoxP3 high Tfr cells were also analyzed. Clinical indicators, including serum Ig and autoantibody levels, were tested, and correlations with Tfr cells were systematically analyzed. The Disease Activity Score in 28 joints ( DAS 28) was calculated, and correlation analysis with Tfr cells was conducted. Results The level of CD 4+ CXCR 5+FoxP3+ Tfr cells and the Tfr cell:Tfh cell ratio in peripheral blood from patients with RA in stable remission were significantly increased compared with the same measures in patients with active RA and in healthy controls. The function of Tfr cells was enhanced, and the activated CD 45 RA −FoxP3 high Tfr cell subset was increased in patients with RA in stable remission compared with healthy controls. Furthermore, the number of Tfr cells in RA patients was inversely correlated with IgG, rheumatoid factor, and anti–cyclic citrullinated peptide as well as with the DAS 28. Conclusion Circulating Tfr cells are increased as patients with RA achieve stable remission of disease, and increased Tfr cells can suppress autoimmunity in RA patients to stabilize their condition. Our results provide novel insight into RA pathogenesis.