tbuckley/cabot-search huggingface dataset:
Desmin- and vimentin-mediated hepatic stellate cell-targeting radiotracer <sup>99m</sup>Tc-GlcNAc-PEI for liver fibrosis imaging with SPECT
Authors: Deliang Zhang, Rongqiang Zhuang, Zhide Guo, Mengna Gao, Lumei Huang, Linyi You, Pu Zhang, Jindian Li, Xinhui Su, Hua Wu, Xiaoyuan Chen, Xianzhong Zhang
Journal: Theranostics (2018)

Extracellular matrix (ECM) accumulation in liver fibrosis is caused by the activation of hepatic stellate cells (HSCs).The goal of this study was to develop a 99m Tc-labeled N-acetylglucosamine (GlcNAc) that specifically interacts with desmin and vimentin expressed on activated HSCs to monitor the progression and prognosis of liver fibrosis using single-photon emission computed tomography (SPECT) imaging.Methods: GlcNAc-conjugated polyethylenimine (PEI) was first prepared and radiolabeled with 99m Tc.Noninvasive SPECT imaging with 99m Tc-GlcNAc-PEI was used to assess liver fibrosis in a carbon tetrachloride (CCl4) mouse model.The liver uptake value (LUV) of 99m Tc-GlcNAc-PEI was measured by drawing the region of interest (ROI) of the whole liver as previously suggested.The LUV of the CCl4 groups was compared with that of the olive oil group.Next, we estimated the correlation between the results of SPECT imaging and physiological indexes.After treatment with clodronate liposome, the LUV of 99m Tc-GlcNAc-PEI in fibrotic mice was compared with that in control mice.Results: 99m Tc-GlcNAc-PEI is a hydrophilic compound with high radiochemical purity (>98%) and good stability.It could specifically target desmin and vimentin on the surface of activated HSCs with high affinity (the Kd values were 53.75 ± 9.50 nM and 20.98 ± 3.56 nM, respectively).The LUV of 99m Tc-GlcNAc-PEI was significantly different between the CCl4 and control groups as early as 4 weeks of CCl4 administration (3.30 ± 0.160 vs 2.34 ± 0.114%/cc; P ˂ 0.05).There was a strong correlation between the LUV and Sirius Red quantification (R = 0.92, P ˂ 0.001).Compared with control, clodronate liposome treatment reduced the LUV of 99m Tc-GlcNAc-PEI (4.62 ± 0.352 vs 2.133 ± 0.414%/cc; P ˂ 0.05).Conclusion: 99m Tc-GlcNAc-PEI SPECT/CT was useful in assessing liver fibrosis and monitoring the treatment response.
USE OF DRUGS WITH BLOOD PRESSURE (BP) LOWERING PROPERTIES AND OUTCOMES IN PATIENTS WITH HEART FAILURE AND PRESERVED EJECTION FRACTION (HFPEF) AND LOW SYSTOLIC BP (SBP)
Authors: Apostolos Tsimploulis, Phillip Lam, Amiya Ahmed, Helen Sheriff, Charles Faselis, Charity Morgan, Gregg C. Fonarow, Ali Ahmed
Journal: Journal of the American College of Cardiology (2018)
SAFETY AND EFFICACY OF THE COMBO BIO-ENGINEERED STENT IN PATIENTS AT HIGH BLEEDING RISK: RESULTS FROM THE MASCOT POST-MARKETING REGISTRY
Authors: Roxana Mehran, Jaya Chandrasekhar, Melissa Aquino, Sabato Sorrentino, Tiong Kiam Ong, Michael Kang Yin Lee, Andres Iniguez, Hazem Warda, Kamilia Moalem, Clayton Snyder, Debbie Morrell, Francesca Elmore, Stephen Rowland, Antonio Colombo
Journal: Journal of the American College of Cardiology (2018)
BMA requests urgent meeting with Treasury on pensions
Authors: Ingrid Torjesen
Journal: BMJ (2012)

The BMA has written to the chief secretary to the Treasury requesting an urgent meeting on the future of the NHS pension scheme in an attempt to re-start talks with the government on proposed changes to the scheme.

Talks with the government have effectively stalled and the BMA is keen to continue dialogue rather than resorting to a ballot on industrial action (doi:10.1136/bmj.e1049).

In the letter to chief secretary, Danny Alexander, the BMA points out that the NHS pension scheme is in a very different situation from other public sector schemes, having been …
Cryptic Species – More Than Terminological Chaos: A Reply to Heethoff
Authors: Torsten H. Struck, Jeffrey L. Feder, Mika Bendiksby, Siri Birkeland, Jose Cerca, Vladimir I. Gusarov, Sonja Kistenich, Karl-Henrik Larsson, Lee Hsiang Liow, Michael D. Nowak, Brita Stedje, Lutz Bachmann, Dimitar Dimitrov
Journal: Trends in Ecology & Evolution (2018)
Abstract P3-07-01: IRS1 expression is required for estrogen stimulated growth in breast cancer cells
Authors: X Zhang, S Varma, D Yee
Journal: Cancer Research (2018)

Abstract Insulin receptor substrate (IRS) proteins are adaptor proteins phosphorylated by activated type I insulin-like growth factor receptor (IGF-1R) and insulin receptor (IR). In addition to their roles in normal cell physiology, we have shown IRS expression is required for breast cancer cell growth and motility. IRS1 plays a more important role in mitogenesis and survival while IRS2 in cancer cell metastasis. Moreover, this family of adaptor proteins is also involved in the signal transduction of many other transmembrane receptors. Thus, IRS proteins could be potential cancer therapeutic targets. We have previously shown that reduced IRS1 impairs IGF and insuliln stimulated cancer cell growth and tumorigenicity even when signaling is not affected due to possible compensation of IRS2 and other adaptor proteins. To further study the role of IRS-1 function in breast cancer, we created doxycycline inducible IRS-1 shRNA cells. We also found that IRS1 knockdown significantly reduced estradiol stimulated growth. To investigate if reduced IRS1 regulated E2 stimulated binding of ERa ChIP assay was performed using the pS2 promoter. Compared to parental MCF-7L cells, inducible IRS1 knock down clone 3G5 demonstrated significantly reduced promoter binding. Degradation of IRS-1 with a pharmacologic antagonist (NT-157) also diminished ERa binding to pS2 promoter. Further qRT-PCR analysis for mRNA levels of estrogen regulated genes, such as PGR, TFF1, etc. showed those genes were significantly down regulated. To evaluate effects of IRS-1 levels on estrogen stimulated growth, we evaluated 3G5-B12 (a subclone of 3G5) cell growth in a xenograft model. 3G5-B12 cells have similar levels of IGFIR and ERa expression compared to their parent cells. Estrogen dependent xenograft growth was similar to those of parent MCF-7L cells. After doxycycline was administered in the diet, 3G5-B12 tumor growth was significantly inhibited compared to those fed with normal mouse diet, and this inhibition was prolonged at least 2 and a half months. Parental MCF-7L tumor growth was not affected by the doxycycline diet. Doxycycline inducible IRS1 knock down significantly prolonged the time before tumors reached 1000mm3 compared with those tumors on a normal diet. In conclusion, IRS-1 is required for optimal estrogen receptor function as measured by promoter binding and xenograft growth. Our data suggested suppression of IRS-1 function may target several growth pathways in breast cancer cells and represents a new drug target. Citation Format: Zhang X, Varma S, Yee D. IRS1 expression is required for estrogen stimulated growth in breast cancer cells [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 P3-07-01.
Doctors as Patients
Authors: Diana Pringle
Journal: BMJ (2006)

<b>Objective: </b> To differentiate frontotemporal dementia (FTD) subtypes from each other and from probable Alzheimer disease (AD) using neuropsychological tests. <b>Methods: </b> Patients with FTD and AD (n = 109) were studied with a comprehensive neuropsychological protocol at first contact. Data were subjected to a principal components analysis (PCA) to extract core neuropsychological features. A five-factor solution accounted for 72.89% of the variance and yielded factors related to declarative memory, working memory/visuoconstruction, processing speed/mental flexibility, lexical retrieval, and semantic memory. <b>Results: </b> Between- and within-group analyses revealed that patients with AD obtain their lowest scores on tests of declarative memory while semantic dementia (SemD) patients are particularly disadvantaged on tests of semantic memory. On tests of processing speed/mental flexibility time to completion was faster for social comportment/dysexecutive (SOC/EXEC) patients, but these patients made more errors on some tests. Patients with corticobasal degeneration (CBD) and progressive nonfluent aphasia (PNFA) were impaired on tests of working memory. Logistic regression analyses using factor scores successfully assigned FTD subgroups and AD patients into their respective diagnostic categories. <b>Conclusion: </b> Patients with differing frontotemporal dementia phenotypes can be distinguished from each other and from Alzheimer disease using neuropsychological tests.
Over to you
Authors: Graham Easton
Journal: BMJ (2005)

This week's issue is a great example of how you give this journal its voice. Every article, opinion piece, column, and letter came from readers who felt strongly that they had something to say. We didn't have to ask for any of it. So if you've got something to say and would like to write for us, this week's content might spur you into action.

Sanjay Suman was …
Nanofibered Gelatin‐Based Nonwoven Elasticity Promotes Epithelial Histogenesis
Authors: Nicole Jedrusik, Christoph Meyen, Günter Finkenzeller, G. Björn Stark, Stephan Meskath, Simon Daniel Schulz, Thorsten Steinberg, Philipp Eberwein, Sandra Strassburg, Pascal Tomakidi
Journal: Advanced Healthcare Materials (2018)

Abstract Regarding tissue regeneration, mechanics of biomaterials gains progressive importance. Therefore, this study reports on in situ crosslinked electrospun gelatin nonwoven mats (NWMs) whose distinct modulus of elasticity (ME) promotes epithelial tissue formation in a graded manner. NWMs, comprising fiber diameters in various distributions, yield an ME of about 2.1, 3.2, and 10.9 kPa. A two‐step approach of preclinical in vitro validation identifies the elasticity of 3.2 kPa as superior to the other, regarding the histogenetic epithelial outcome. Hence, this 3.2 kPa candidate NWM is colonized with oral mucosal epithelial keratinocytes in the absence or presence of mesenchymal fibroblasts and/or endothelial cells. Evaluation of epithelial histogenesis at days 1 to 10 occurs by colorimetric and fluorescence‐based immunohistochemistry (IHCH) of specific biomarkers. These include cytokeratins (CK) 14, CK1, and involucrin that indicate different stages of epithelial differentiation, as well as the basement membrane constituent collagen type IV and Ki‐67 as a proliferation marker. Intriguingly, histogenesis and IHCH reveal the best resemblance of the native epithelium by the NWM alone, irrespective of other cell counterparts. These findings prove the gelatin NWM a convenient cell matrix, and evidence that NWM mechanics is important to promote epithelial histogenesis in view of prospective clinical applications.
More than half of trainees and new GPs think specialty training limits doctors’ potential
Authors: Helen Jaques
Journal: BMJ (2013)

More than half of junior doctors and newly qualified GPs who completed an annual BMA survey think that the Modernising Medical Careers (MMC) specialty training programme limits doctors’ potential.1

Each year the BMA surveys a cohort of 435 doctors who graduated in 2006. This was the first group of medical graduates to follow the MMC pathway. When the 368 doctors who responded to the 2012 survey (85% response rate) were asked about aspects of the MMC programme, 54% agreed or strongly agreed …
Reactive species balance via GTP cyclohydrolase I regulates glioblastoma growth and tumor initiating cell maintenance
Authors: Anh Nhat Tran, Kiera Walker, David G Harrison, Wei Chen, James Mobley, Lauren Hocevar, James R Hackney, Randee S Sedaka, Jennifer S Pollock, Matthew S Goldberg, Dolores Hambardzumyan, Sara J Cooper, Yancey Gillespie, Anita B Hjelmeland
Journal: Neuro-Oncology (2018)

Depending on the level, differentiation state, and tumor stage, reactive nitrogen and oxygen species inhibit or increase cancer growth and tumor initiating cell maintenance. The rate-limiting enzyme in a pathway that can regulate reactive species production but has not been thoroughly investigated in glioblastoma (GBM; grade IV astrocytoma) is guanosine triphosphate (GTP) cyclohydrolase 1 (GCH1). We sought to define the role of GCH1 in the regulation of GBM growth and brain tumor initiating cell (BTIC) maintenance. We examined GCH1 mRNA and protein expression in patient-derived xenografts, clinical samples, and glioma gene expression datasets. GCH1 levels were modulated using lentiviral expression systems, and effects on cell growth, self-renewal, reactive species production, and survival in orthotopic patient-derived xenograft models were determined. GCH1 was expressed in GBMs with elevated but not exclusive RNA and protein levels in BTICs in comparison to non-BTICs. Overexpression of GCH1 in GBM cells increased cell growth in vitro and decreased survival in an intracranial GBM mouse model. In converse experiments, GCH1 knockdown with short hairpin RNA led to GBM cell growth inhibition and reduced self-renewal in association with decreased CD44 expression. GCH1 was critical for controlling reactive species balance, including suppressing reactive oxygen species production, which mediated GCH1 cell growth effects. In silico analyses demonstrated that higher GCH1 levels in glioma patients correlate with higher glioma grade, recurrence, and worse survival. GCH1 expression in established GBMs is pro-tumorigenic, causing increased growth due, in part, to promotion of BTIC maintenance and suppression of reactive oxygen species.
Reliability and validity of the instrument for scoring clinical outcomes of research for epidermolysis bullosa (iscorEB)
Authors: A.L. Bruckner, D.L. Fairclough, J.A. Feinstein, I. Lara-Corrales, A.W. Lucky, J. Tolar, E. Pope
Journal: British Journal of Dermatology (2018)

Epidermolysis bullosa (EB) is a group of rare and currently incurable genetic blistering disorders. As more pathogenic-driven therapies are being developed, there is an important need for EB-specific validated outcomes measures designed for use in clinical trials.To test the reliability and construct validity of an instrument for scoring clinical outcomes of research for EB (iscorEB), a new combined clinician- and patient-reported outcomes tool.We conducted an observational study consisting of independent 1-day assessments (six assessors) at two academic hospitals. The assessments consisted of iscorEB clinician (iscorEB-c), Birmingham Epidermolysis Bullosa Severity (BEBS) and global severity assessment for physicians; and iscorEB patient (iscorEB-p), Quality of Life evaluation in Epidermolysis Bullosa and Children's Dermatology Life Quality Index for patients. Construct validity and intraclass correlation coefficients (ICCs) for interobserver, intraobserver and test-retest reliability were calculated.Overall, 31 patients with a mean age of 19·5 years (1·8-45·2) were included. Disease severity was mild in 42% of cases, moderate in 29% and severe in 29%. The interobserver ICC was 0·96 for both the clinician-reported section of iscorEB-c and BEBS. The ICC for intraobserver reliability was 0·91 and 0·70 for the skin and mucosal domains of iscorEB-c, respectively. Cronbach's alpha for iscorEB-c was 0·89. The test-retest reliability of iscorEB-p was 0·97 and Cronbach's alpha was 0·84. The clinical score differentiated between subjects with mild, moderate and severe disease, and both clinical and patient subscores discriminated between recessive dystrophic EB and other EB subtypes.iscorEB has robust reliability and construct validity, including strong ability to distinguish EB types and severities. Further studies are planned to test its responsiveness to change.
ASSOCIATION BETWEEN C-REACTIVE PROTEIN AND THE RISK OF ATRIAL FIBRILLATION IN THE GENERAL POPULATION: ANSAN AND ANSUNG COHORT OF THE KOREAN GENOME AND EPIDEMIOLOGY STUDY
Authors: Jinkyu Park, Yonggu Lee, Hwan-Cheol Park, Jeong-Hun Shin, Young-Hyo Lim, Jinho Shin
Journal: Journal of the American College of Cardiology (2018)
Preclinical efficacy of dendritic cells derived from bone marrow hematopoietic stem cells for the treatment of syngeneic prostate cancer immune cell therapy.
Authors: Yunlim Kim, Choung-Soo Kim, Bongmin Kim
Journal: Journal of Clinical Oncology (2018)

361 Background: PCas are characterized by a primary androgen dependent stage, during which growth is promoted by androgen and suppressed by androgen deprivation or blockade, with even metastatic disease being promptly susceptible to hormonal manipulation; however, despite initial success, androgen deprivation therapy eventually fails because of the development of CRPC. Despite the approval of new clinical trials such as docetaxel, enzalutamide and sipuleucel-T, which is a cell therapy drug, the clinical efficacy is limited. Therefore, there is a desperate need for the limited effectiveness of treatment in an aging society and the development of successful treatments for patients who fail treatment. In this study, we investigated the anticancer effect of prostate cancer using anti-cancer immunity cell vaccine based on the next generation dendritic cell immunotherapy. Methods: FACS and ELISA were performed with stem-DC to analyze phenotype and cytokine expression. To quantify the effect on the tumor growth, we constructed a TRAMP-C1 model and observed for safety, efficacy and induction of antigen-specific immune responses. And we also analyzed proliferation and activation of allogeneic-T cells by therapeutic dendritic cells. Results: From the stem-DC, immune-stimulatory cytokine IL-12 and interferone-gamma was measured higher level than monocyte derived DC (Mo-DC). A DC marker CD11c+CD8a+ cell was higher expression in stem-DC than Mo-DC. After DC injection, tumor size was reduced in stem-DC compared to Mono-DC and vehicle group in TRAMP model. To confirm stem-DC/lysate induce more systemic anti-tumor immunity than Mo-DC/lysate, we checked effector T cells in splenic lymphocytes from prostate cancer bearing mice. The frequency of IFN-γ secreting CD8+ T cells in stem-DC treated group was significantly higher than that in Mo-DC treated group. It shows that the therapeutic responses were associated with induction of IFN-γ secreting CD8+ T cells. Conclusions: Stem-DC, which was developed from hematopoietic stem cells in an optimized manner, proved to be effective and stable as an excellent anti-cancer immunotherapeutic agent for prostate cancer.
India’s Call to Action—Prioritize Chronic Cardiovascular Disease
Authors: Alka M. Kanaya
Journal: JAMA Internal Medicine (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Socioeconomic inequalities in childhood and adolescent body-mass index, weight, and height from 1953 to 2015: an analysis of four longitudinal, observational, British birth cohort studies
Authors: David Bann, William Johnson, Leah Li, Diana Kuh, Rebecca Hardy
Journal: The Lancet Public Health (2018)

Socioeconomic inequalities in childhood body-mass index (BMI) have been documented in high-income countries; however, uncertainty exists with regard to how they have changed over time, how inequalities in the composite parts (ie, weight and height) of BMI have changed, and whether inequalities differ in magnitude across the outcome distribution. Therefore, we aimed to investigate how socioeconomic inequalities in childhood and adolescent weight, height, and BMI have changed over time in Britain.
The World Health Organization standards for tuberculosis care and management
Authors: Christopher Gilpin, Alexei Korobitsyn, Giovanni Battista Migliori, Mario C. Raviglione, Karin Weyer
Journal: European Respiratory Journal (2018)

Tuberculosis (TB) is a global public health priority, with 10.4 million people developing the disease in 2016 (10% among HIV co-infected individuals), 1.67 million deaths and 490 000 multidrug-resistant (MDR) plus an additional 110 000 rifampicin-resistant cases [1]. The WHO TB Compendium facilitates the delivery of high-quality care to all persons affected by TB <http://ow.ly/VzsM30iO8sO> The contributors to the Compendium are Annabel Baddeley, Annemieke Brands, Monica Dias, Dennis Falzon, Haileyesus Getahun, Christopher Gilpin, Philippe Glaziou, Malgosia Grzemska, Yohhei Hamada, Ernesto Jaramillo, Alexei Korobitsyn, Knut Lönnroth, Fuad Mirzayev, Linh Nguyen, Kefas Samson, Lana Syed, Mario Raviglione, Hazim Timimi, Mukund Uplekar, Wayne van Gemert, Diana Weil, Karin Weyer and Matteo Zignol (all Global Tuberculosis Programme, WHO, Geneva, Switzerland).
A professor of tropical medicine and infectious diseases
Authors: Rameen Shakur
Journal: BMJ (2005)

P rofessor David Warrell has been a leading figure in tropical medicine and a bastion of academic medicine in the United Kingdom for the last 30 years. As the professor of tropical medicine and infectious diseases and past head of the Nuffield Department of Clinical Medicine at the University of Oxford, he has a unique insight into the life of an academic physician. He is also the main editor of the revised Oxford Textbook of Medicine , which remains the definitive medical textbook for many people in medicine. Rameen Shakur asked Professor Warrell about his journey into academic medicine and what advice he would give to anyone interested in such a career.

I was born in Singapore where my father was in the Admiralty. However, we were bombed by the Japanese both in Singapore harbour in late …