tbuckley/cabot-search huggingface dataset:
Different doses of Pilates-based exercise therapy for chronic low back pain: a randomised controlled trial with economic evaluation
Authors: Gisela Cristiane Miyamoto, Katherinne Ferro Moura Franco, Johanna M van Dongen, Yuri Rafael dos Santos Franco, Naiane Teixeira Bastos de Oliveira, Diego Diulgeroglo Vicco Amaral, Amanda Nery Castelo Branco, Maria Liliane da Silva, Maurits W van Tulder, Cristina Maria Nunes Cabral
Journal: British Journal of Sports Medicine (2018)

Objectives To evaluate the effectiveness and cost-utility of the addition of different doses of Pilates to an advice for non-specific chronic low back pain (NSCLBP) from a societal perspective. Design Randomised controlled trial with economic evaluation. Setting Physiotherapy clinic in São Paulo, Brazil. Participants 296 patients with NSCLBP. Interventions All patients received advice and were randomly allocated to four groups (n=74 per group): booklet group (BG), Pilates once a week (Pilates group 1, PG1), Pilates twice a week (Pilates group 2, PG2) and Pilates three times a week (Pilates group 3, PG3). Main outcome measures Primary outcomes were pain and disability at 6-week follow-up. Results Compared with the BG, all Pilates groups showed significant improvements in pain (PG1, mean difference (MD)=−1.2, 95% CI −2.2 to −0.3; PG2, MD=−2.3, 95% CI −3.2 to −1.4; PG3, MD=−2.1, 95% CI −3.0 to −1.1) and disability (PG1, MD=−1.9, 95% CI −3.6 to −0.1; PG2, MD=−4.7, 95% CI −6.4 to −3.0; PG3, MD=−3.3, 95% CI −5.0 to −1.6). Among the different doses, PG2 showed significant improvements in comparison with PG1 for pain (MD=−1.1, 95% CI −2.0 to −0.1) and disability (MD=−2.8, 95% CI −4.5 to −1.1). The cost-utility analysis showed that PG3 had a 0.78 probability of being cost-effective at a willingness-to-pay of £20 000 per quality-adjusted life-year gained. Conclusions Adding two sessions of Pilates exercises to advice provided better outcomes in pain and disability than advice alone for patients with NSCLBP; non-specific elements such as greater attention or expectation might be part of this effect. The cost-utility analysis showed that Pilates three times a week was the preferred option. Trial registration number NCT02241538 , Completed.
TREM2 Is a Receptor for β-Amyloid that Mediates Microglial Function
Authors: Yingjun Zhao, Xilin Wu, Xiaoguang Li, Lu-Lin Jiang, Xun Gui, Yan Liu, Yu Sun, Bing Zhu, Juan C. Piña-Crespo, Muxian Zhang, Ningyan Zhang, Xiaochun Chen, Guojun Bu, Zhiqiang An, Timothy Y. Huang, Huaxi Xu
Journal: Neuron (2018)
Evidence for the ISG15-Specific Deubiquitinase USP18 as an Antineoplastic Target
Authors: Lisa Maria Mustachio, Yun Lu, Masanori Kawakami, Jason Roszik, Sarah J. Freemantle, Xi Liu, Ethan Dmitrovsky
Journal: Cancer Research (2018)

Abstract Ubiquitination and ubiquitin-like posttranslational modifications (PTM) regulate activity and stability of oncoproteins and tumor suppressors. This implicates PTMs as antineoplastic targets. One way to alter PTMs is to inhibit activity of deubiquitinases (DUB) that remove ubiquitin or ubiquitin-like proteins from substrate proteins. Roles of DUBs in carcinogenesis have been intensively studied, yet few inhibitors exist. Prior work provides a basis for the ubiquitin-specific protease 18 (USP18) as an antineoplastic target. USP18 is the major DUB that removes IFN-stimulated gene 15 (ISG15) from conjugated proteins. Prior work discovered that engineered loss of USP18 increases ISGylation and in contrast to its gain decreases cancer growth by destabilizing growth-regulatory proteins. Loss of USP18 reduced cancer cell growth by triggering apoptosis. Genetic loss of USP18 repressed cancer formation in engineered murine lung cancer models. The translational relevance of USP18 was confirmed by finding its expression was deregulated in malignant versus normal tissues. Notably, the recent elucidation of the USP18 crystal structure offers a framework for developing an inhibitor to this DUB. This review summarizes strong evidence for USP18 as a previously unrecognized pharmacologic target in oncology. Cancer Res; 78(3); 587–92. ©2018 AACR.
HIGH-RISK PLAQUE IN NON-OBSTRUCTIVE CORONARY ARTERY DISEASE CONFERS RISK SIMILAR TO OBSTRUCTIVE DISEASE WITHOUT HIGH-RISK FEATURES: THE ICONIC STUDY
Authors: Richard Anthony Ferraro, Fay Lin, Jessica Peña, Daniele Andreini, Filippo Cademartiri, Kavitha Chinnaiyan, Benjamin Chow, Ricardo Cury, Gudrun Feuchtner, Martin Hadamitzky, Yong-Jin Kim, Jonathon Leipsic, Hugo Marques, Gianluca Pontone, Gilbert Raff, Todd Villines, Peter Stone, Habib Samady, Renu Virmani, Jagat Narula, Jeroen J. Bax, James K. Min, Hyuk-Jae Chang
Journal: Journal of the American College of Cardiology (2018)
Government to increase retirement age and axe final salary pensions
Authors: Helen Jaques
Journal: BMJ (2011)

The government has laid out plans to increase the retirement age for public sector employees and replace final salary pensions with career average schemes.

The chief secretary to the Treasury, Danny Alexander, has confirmed that the age at which public sector workers will be able to draw their pensions will rise to 66 by 2020, in line with changes to the private sector retirement age.

Staff in the public sector will be moved to career average schemes, as suggested by Lord Hutton in his review of public sector pensions earlier this year, although benefits accrued under existing final salary schemes will be protected.

Pension contributions will …
18F-FDG PET/CT Equivalent of the Hepatic Hot Spot Sign With CT Correlation
Authors: Michael C. Jundt, Stephen M. Broski, Larry A. Binkovitz
Journal: Clinical Nuclear Medicine (2018)

A 43-year-old woman presented with an FDG-avid mediastinal Ewing sarcoma invading and nearly occluding the superior vena cava. Geographic increased FDG uptake in hepatic segment IVA was the only other site of nonphysiologic FDG activity. This focal activity was without an underlying mass, had atypical morphology for a hepatic metastasis, and correlated well with prior CT findings of abnormal segment IVA enhancement resulting from the recruitment of portocaval collaterals. In the correct setting, the F-FDG hepatic hot spot should be considered in the differential of a focal FDG-avid hepatic lesion in segment IVA.
GENDER SPECIFIC FACTORS ASSOCIATED WITH MAJOR ADVERSE CARDIOVASCULAR EVENTS: INSIGHTS FROM ACCELERATE
Authors: Peta King, Paul Cremer, Stephen Nicholls, A. Lincoff, Venu Menon, Jeffrey Riesmeyer, Giacomo Ruotolo, Julie St John, Ellen McErlean, Steven Nissen
Journal: Journal of the American College of Cardiology (2018)
Cytokine Responses to Rhinovirus and Development of Asthma, Allergic Sensitization, and Respiratory Infections during Childhood
Authors: Adnan Custovic, Danielle Belgrave, Lijing Lin, Eteri Bakhsoliani, Aurica G. Telcian, Roberto Solari, Clare S. Murray, Ross P. Walton, John Curtin, Michael R. Edwards, Angela Simpson, Magnus Rattray, Sebastian L. Johnston
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Rationale: Immunophenotypes of antiviral responses, and their relationship with asthma, allergy, and lower respiratory tract infections, are poorly understood.Objectives: We characterized multiple cytokine responses of peripheral blood mononuclear cells to rhinovirus stimulation, and their relationship with clinical outcomes.Methods: In a population-based birth cohort, we measured 28 cytokines after stimulation with rhinovirus-16 in 307 children aged 11 years. We used machine learning to identify patterns of cytokine responses, and related these patterns to clinical outcomes, using longitudinal models. We also ascertained phytohemagglutinin-induced T-helper cell type 2 (Th2)-cytokine responses (PHA-Th2).Measurements and Main Results: We identified six clusters of children based on their rhinovirus-16 responses, which were differentiated by the expression of four cytokine/chemokine groups: interferon-related (IFN), proinflammatory (Inflam), Th2-chemokine (Th2-chem), and regulatory (Reg). Clusters differed in their clinical characteristics. Children with an IFNmodInflamhighestTh2-chemhighestReghighest rhinovirus-16–induced pattern had a PHA-Th2low response, and a very low asthma risk (odds ratio [OR], 0.08; 95% confidence interval [CI], 0.01–0.81; P = 0.03). Two clusters had a high risk of asthma and allergic sensitization, but with different trajectories from infancy to adolescence. The IFNlowestInflamhighTh2-chemlowRegmod cluster exhibited a PHA-Th2lowest response and was associated with early-onset asthma and sensitization, and the highest risk of asthma exacerbations (OR, 1.37; 95% CI, 1.07–1.76; P = 0.014) and lower respiratory tract infection hospitalizations (OR, 2.40; 95% CI, 1.26–4.58; P = 0.008) throughout childhood. In contrast, the IFNhighestInflammodTh2-chemmodReghigh cluster with a rhinovirus-16–cytokine pattern was characterized by a PHA-Th2highest response, and a low prevalence of asthma/sensitization in infancy that increased sharply to become the highest among all clusters by adolescence (but with a low risk of asthma exacerbations).Conclusions: Early-onset troublesome asthma with early-life sensitization, later-onset milder allergic asthma, and disease protection are each associated with different patterns of rhinovirus-induced immune responses.
Sarcoma-Targeting Peptide-Decorated Polypeptide Nanogel Intracellularly Delivers Shikonin for Upregulated Osteosarcoma Necroptosis and Diminished Pulmonary Metastasis
Authors: Suoyuan Li, Tao Zhang, Weiguo Xu, Jianxun Ding, Fei Yin, Jing Xu, Wei Sun, Hongsheng Wang, Mengxiong Sun, Zhengdong Cai, Yingqi Hua
Journal: Theranostics (2018)

Osteosarcoma is the most common primary bone cancer and is notorious for pulmonary metastasis, representing a major threat to pediatric patients. An effective drug targeting osteosarcoma and its lung metastasis is urgently needed.In this study, a sarcoma-targeting peptide-decorated disulfide-crosslinked polypeptide nanogel (STP-NG) was exploited for enhanced intracellular delivery of shikonin (SHK), an extract of a medicinal herb, to inhibit osteosarcoma progression with minimal systemic toxicity.The targeted, loaded nanogel, STP-NG/SHK, killed osteosarcoma cells by inducing RIP1- and RIP3-dependent necroptosis in vitro. Necroptosis is a novel cell death form that could be well adapted as an efficient antitumor strategy, the main obstacle of which is its high toxicity. After intravenous injection, STP-NG/SHK efficiently suppressed tumor growth and reduced pulmonary metastasis, offering greater tumor necrosis and higher RIP1 and RIP3 upregulation compared to free SHK or untargeted NG/SHK in vivo. Additionally, the treatment with NG/SHK or STP-NG/SHK showed minimal toxicity to normal organs, suggesting low systemic toxicity compared to free SHK.The STP-guided intracellular drug delivery system using the necroptosis mechanism showed profound anti-osteosarcoma activity, especially eliminated lung metastasis in vivo. This drug formulation may have great potential for treatment of osteosarcoma.
SAS doctors report lack of time for professional development
Authors: Helen Jaques
Journal: BMJ (2012)

Many staff, associate specialist, and specialty (SAS) doctors do not have time for continuing professional development, and a fifth have been refused study leave, a survey by the BMA has found. 

Although around half (56%) of the 361 SAS doctors who responded to the online survey had one supporting professional activity (SPA) spot a week in their job plan, in line with the specialty doctor and associate specialist contracts introduced in April 2008, almost …
Association of <i>STAT6</i> gene variants with food allergy diagnosed by double‐blind placebo‐controlled food challenges
Authors: C. D. van Ginkel, M. E. Pettersson, A. E. J. Dubois, G. H. Koppelman
Journal: Allergy (2018)

This study describes the role of two STAT6 gene variants in food allergy using data of patients and their parents who underwent double-blind placebo-controlled food challenges (DBPCFCs). After quality control, 369 trios were analysed including 262 children (71.0%) with food allergy. Associations were tested by the Family based association test. The A alleles of both SNPs were associated with food allergy (P = .036 and P = .013 for rs324015 and rs1059513, respectively). Furthermore, these A alleles were associated with peanut allergy, higher sIgE levels to both peanut and cow's milk, more severe symptoms and higher eliciting doses during peanut and cow's milk DBPCFCs (all P < .05). In silico analysis indicates that the identified risk variants increase STAT6 expression which stimulates the differentiation of CD4 + T cells to the Th2 subset. In conclusion, STAT6 variants may be involved in the pathophysiology of food allergy and their role seems to be independent of the allergenic food.
IMPORTANCE OF SITE MEASUREMENT ON INTERPRETATION OR FRACTIONAL FLOW RESERVE BY CORONARY COMPUTED TOMOGRAPHY ANGIOGRAPHY: RECLASSIFICATION OF POSITIVE AND NEGATIVE RESULTS
Authors: Elvis Cami, Travis Tagami, Gilbert Raff, Michael Gallagher, A. Neil Bilolikar, Kavitha Chinnaiyan, Austin Fan, Adam Hafeez, Robert Safian
Journal: Journal of the American College of Cardiology (2018)
SPONTANEOUS CORONARY ARTERY DISSECTION: GENDER INFLUENCE ON AGE OF ONSET, AND DRIVERS FOR REVASCULARIZATION WITHIN THE ALBERTA PROVINCIAL PROJECT FOR OUTCOME ASSESSMENT IN CORONARY HEART DISEASE REGISTRY
Authors: Ravi Ramlal, Umair Iiftikhar, Ashim Verma, Lisa Bilston, Bryan Har, Jacqueline Saw
Journal: Journal of the American College of Cardiology (2018)
Doctors should consider benefits of working overseas, BMA says
Authors: Matthew Limb
Journal: BMJ (2013)

UK doctors should view taking time out to work or train overseas, particularly in developing countries, as a “positive career move” that could bring “immeasurable” benefits, the BMA has said.

It has published updated guidance designed to support doctors at all stages of their careers who are considering working or training overseas and to answer concerns they may have (http://bma.org.uk/developing-your-career/career-progression/broaden-your-horizons).

The BMA’s chairman of council, Mark Porter, said it was “more important than ever” for clinicians to gain international experience in developing countries, …
I am currently a third year surgical senior house officer and am finding the work within general practice quite appealing. How difficult would it be to gain access to a GP vocational scheme?
Authors: Ruth Chambers
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.
Silicon Carbide Nanoparticles as an Effective Bioadhesive to Bond Collagen Containing Composite Gel Layers for Tissue Engineering Applications
Authors: Rana Attalla, Celine S. N. Ling, Ponnambalam Ravi Selvaganapathy
Journal: Advanced Healthcare Materials (2018)

Abstract Additive manufacturing via layer‐by‐layer adhesive bonding holds much promise for scalable manufacturing of tissue‐like constructs, specifically scaffolds with integrated vascular networks for tissue engineering applications. However, there remains a lack of effective adhesives capable of composite layer fusion without affecting the integrity of patterned features. Here, the use of silicon carbide is introduced as an effective adhesive to achieve strong bonding (0.39 ± 0.03 kPa) between hybrid hydrogel films composed of alginate and collagen. The techniques have allowed us to fabricate multilayered, heterogeneous constructs with embedded high‐resolution microchannels (150 µm–1 mm) that are precisely interspaced (500–600 µm). Hydrogel layers are effectively bonded with silicon carbide nanoparticles without blocking the hollow microchannels and high cell viability (90.61 ± 3.28%) is maintained within the scaffold. Nanosilica is also tested and found to cause clogging of smaller microchannels when used for interlayer bonding, but is successfully used to attach synthetic polymers (e.g., Tygon) to the hydrogels (32.5 ± 2.12 mN bond strength). This allows us to form inlet and outlet interconnections to the gel constructs. This ability to integrate hollow channel networks into bulk soft material structures for perfusion can be useful in 3D tissue engineering applications.
Comprehensive immune and mutational profile of melanoma.
Authors: Jeffrey M. Conroy, Sarabjot Pabla, Marc S. Ernstoff, Igor Puzanov, Mary Nesline, Sean T. Glenn, Antonios Papanicolau-Sengos, Blake Burgher, Jonathan Andreas, Vincent Giamo, Maochun Qin, Felicia L. Lenzo, Mark Gardner, Carl Morrison
Journal: Journal of Clinical Oncology (2018)

182 Background: The association between tumor mutational profiles and immune signatures has not been well-characterized. Methods: 306 melanoma samples were tested by NGS using a comprehensive cancer panel for mutational status and an immune response panel which interrogates the expression profile of 54 validated immune-related genes. The ranking of gene expression, mutational burden and 7 immune phenotypes was compared to a reference population. 38% cases were positive for activating BRAF mutations, 12% for RAS, and 6% for NF1. The remaining 44% were considered triple wild type. Principal component analysis (PCA) followed by hierarchical clustering was performed to determine association of BRAF/RAS/NF1 mutations and triple wild type with immune phenotypes, mutational burden and gene expression as measured by the NGS panels. Results: PCA showed that the first and second dimension explain 86% of the variation in the mutation profiles of the 306 melanomas. The first principal component highly correlated with BRAF positive status (pval &lt; 0.001), the second highly correlated with RAS positive status (pval &lt; 0.001), and the third principal component, although not informative, highly correlated with NF1 status (pval &lt; 0.001) and Mutation Burden (pval &lt; 0.001). Hierarchical clustering of the samples resulted in 4 distinct clusters: RAS positive, BRAF Positive, NF1 positive and triple wild type. The RAS positive cluster demonstrated significantly lower expression of ICOSLG, ICOS, CD4, C10orf54, CD40 and CD244 genes. Similarly, the BRAF positive cluster under-expresses immune escape and proinflammatory immune phenotypes, but over-expressed OX40L. The NF1 positive cluster had significantly higher mutational burden than other clusters. On the contrary, the triple wild type cluster over-expressed 6 out of 7 immune phenotypes. Conclusions: BRAF/RAS/NF1 mutation status are immunophenotypically distinct and do not associate with a typical immune phenotype in the tumor microenvironment. Triple wild type samples present with an overall activated immune phenotype, representative of an inflamed tumor. Additional studies are necessary to include additional activating or loss of function mutations to expand these findings.
Impact of T2R38 Receptor Polymorphisms on <i>Pseudomonas aeruginosa</i> Infection in Cystic Fibrosis
Authors: Andrew R. Turnbull, Ronan Murphy, Volker Behrends, Helena Lund-Palau, Ameze Simbo, Myril Mariveles, Eric W. F. W. Alton, Andrew Bush, Amelia Shoemark, Jane C. Davies
Journal: American Journal of Respiratory and Critical Care Medicine (2018)
LEFT ATRIAL STRAIN DURING EXERCISE IS A KEY DETERMINANT OF CARDIOVASCULAR EVENT IN PATIENTS WITH NON-ISCHEMIC DILATED CARDIOMYOPATHY
Authors: Makoto Amaki, Yasuhiro Hamatani, Hideaki Kanzaki, Yoshiki Yanagi, Rika Mizuta, Atsushi Okada, Hiroyuki Takahama, Takuya Hasegawa, Yasuo Sugano, Satoshi Yasuda, Toshihisa Anzai
Journal: Journal of the American College of Cardiology (2018)
GPs reject calls to renegotiate contract
Authors: Helen Jaques
Journal: BMJ (2012)

Delegates at the conference of local medical committees have branded proposals to negotiate a new national GP contract as impossible in the current financial climate.

With GPs’ income going down, it is not possible for the BMA to add more elements to the general medical services contract without having to take some items out, said the chairman of the BMA’s General Practitioners Committee, Laurence Buckman.

In addition, said Andrew Townsley, a representative from Glasgow, negotiation is a two way process and requires a receptive government, which is …
THE PROGNOSTIC EFFECT OF KNOWN AND NEWLY DETECTED TYPE 2 DIABETES IN PATIENTS WITH ACUTE CORONARY SYNDROMES
Authors: Thorarinn Arni Bjarnason, Steinar Hafthorsson, Linda Kristinsdottir, Erna Sif Oskarsdottir, Thor Aspelund, Sigurdur Sigurdsson, Vilmundur Gudnason, Karl Andersen
Journal: Journal of the American College of Cardiology (2018)
TDP-43 gains function due to perturbed autoregulation in a Tardbp knock-in mouse model of ALS-FTD
Authors: Matthew A. White, Eosu Kim, Amanda Duffy, Robert Adalbert, Benjamin U. Phillips, Owen M. Peters, Jodie Stephenson, Sujeong Yang, Francesca Massenzio, Ziqiang Lin, Simon Andrews, Anne Segonds-Pichon, Jake Metterville, Lisa M. Saksida, Richard Mead, Richard R Ribchester, Youssef Barhomi, Thomas Serre, Michael P. Coleman, Justin R. Fallon, Timothy J. Bussey, Robert H. Brown, Jemeen Sreedharan
Journal: Nature Neuroscience (2018)
“Crisis” in NHS leadership needs urgent action, says Institute of Healthcare Management
Authors: Matthew Limb
Journal: BMJ (2016)

Urgent action is needed to tackle a “leadership crisis” in the NHS and bring down barriers that deter would-be leaders from rising through the ranks, a report by the Institute of Healthcare Management has concluded.

A survey by the institute, an independent membership organisation for health and social care managers, found that aspiration to top level NHS positions remained high among management and leadership trainees. But many were being put off by “unrealistic demands” and believed that they wouldn’t be empowered to make change even once in post.

In the report the institute said, “It is fair to suggest that measures to address the leadership crisis will be akin to rearranging the deckchairs on the Titanic unless the overall leadership offer can be made more attractive.”

Shirley Cramer, the institute’s chief executive, said, “Above all, we need to empower and back those who …
APPLICATION OF ARTIFICIAL INTELLIGENCE TO THE STANDARD 12 LEAD ECG TO IDENTIFY PEOPLE WITH LEFT VENTRICULAR DYSFUNCTION
Authors: Zachi Itzhak Attia, Suraj Kapa, Francisco Lopez-Jimenez, Paul McKie, Dorothy Ladewig, Gaurav Satam, Patricia Pellikka, Thomas Munger, Samuel Asirvatham, Serban Dronca, Christopher Scott, Rickey Carter, Paul Friedman
Journal: Journal of the American College of Cardiology (2018)
MORTALITY AND CLINICAL OUTCOMES AFTER FIBRINOLYSIS IN A POPULATION WITH ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION: A CONTEMPORARY STUDY OF THE TIMING OF CORONARY INTERVENTIONS AFTER FIBRINOLYSIS IN A RURAL POPULATION
Authors: Kristy Webster, Danette Flint, Sheila Conley, Nathaniel Niles
Journal: Journal of the American College of Cardiology (2018)