tbuckley/cabot-search huggingface dataset:
Synthetic Biomaterials to Rival Nature's Complexity—a Path Forward with Combinatorics, High‐Throughput Discovery, and High‐Content Analysis
Authors: Douglas Zhang, Junmin Lee, Kristopher A. Kilian
Journal: Advanced Healthcare Materials (2017)

Abstract Cells in tissue receive a host of soluble and insoluble signals in a context‐dependent fashion, where integration of these cues through a complex network of signal transduction cascades will define a particular outcome. Biomaterials scientists and engineers are tasked with designing materials that can at least partially recreate this complex signaling milieu towards new materials for biomedical applications. In this progress report, recent advances in high throughput techniques and high content imaging approaches that are facilitating the discovery of efficacious biomaterials are described. From microarrays of synthetic polymers, peptides and full‐length proteins, to designer cell culture systems that present multiple biophysical and biochemical cues in tandem, it is discussed how the integration of combinatorics with high content imaging and analysis is essential to extracting biologically meaningful information from large scale cellular screens to inform the design of next generation biomaterials.
Pharmacological and Activated Fibroblast Targeting of Gβγ-GRK2 After Myocardial Ischemia Attenuates Heart Failure Progression
Authors: Joshua G. Travers, Fadia A. Kamal, Iñigo Valiente-Alandi, Michelle L. Nieman, Michelle A. Sargent, John N. Lorenz, Jeffery D. Molkentin, Burns C. Blaxall
Journal: Journal of the American College of Cardiology (2017)
Queen Mary University London: one of the longest established masters of sport and exercise medicine globally (continuing professional development series)
Authors: Simon Lack, Aleksandra Birn-Jeffery, Ian Beasley, Dylan Morrissey
Journal: British Journal of Sports Medicine (2017)

Sports and Exercise Medicine, William Harvey Research Institute, School of Medicine and Dentistry, Queen Mary University London (QMUL), London, UK.

Master of Science (MSc) in Sports and Exercise Medicine.

With the continued growth of sports participation, both recreationally and professionally, the expectation for the highest level of health provision is also set to grow. Completion of a Masters in Sports and Exercise Medicine (SEM), to inform evidence-based medicine delivery and demonstrate professional competencies, is increasingly becoming a requirement within these sporting environments.1 

The SEM Masters programme is open to nationally and internationally qualified medical doctors, physiotherapists, osteopaths and podiatrists (table 1). As the longest established SEM MSc in Europe (and possibly the world), the programme has a prestigious history. The vision of Professor John King, as course founder >30 years ago, was to provide the best possible SEM training and to inspire the next generation of SEM expert clinician scientists. Graduates include the Chief Medical Officers for Team Great Britain at the Beijing 2008 and London 2012 Olympic and Paralympic games, and the Greek team at Athens 2004.

View this table:

Table 1 
Key facts …
Quantitative Whole Genome Sequencing of Circulating Tumor Cells Enables Personalized Combination Therapy of Metastatic Cancer
Authors: Natali Gulbahce, Mark Jesus M. Magbanua, Robert Chin, Misha R. Agarwal, Xuhao Luo, Jia Liu, Daniel M. Hayden, Qing Mao, Serban Ciotlos, Zhenyu Li, Yanxiang Chen, Xingpeng Chen, Yuxiang Li, Rebecca Yu Zhang, Katharine Lee, Rick Tearle, Emily Park, Snezana Drmanac, Hope S. Rugo, John W. Park, Radoje Drmanac, Brock A. Peters
Journal: Cancer Research (2017)

Abstract Much effort has been dedicated to developing circulating tumor cells (CTC) as a noninvasive cancer biopsy, but with limited success as yet. In this study, we combine a method for isolation of highly pure CTCs using immunomagnetic enrichment/fluorescence-activated cell sorting with advanced whole genome sequencing (WGS), based on long fragment read technology, to illustrate the utility of an accurate, comprehensive, phased, and quantitative genomic analysis platform for CTCs. Whole genomes of 34 CTCs from a patient with metastatic breast cancer were analyzed as 3,072 barcoded subgenomic compartments of long DNA. WGS resulted in a read coverage of 23× per cell and an ensemble call rate of &amp;gt;95%. These barcoded reads enabled accurate detection of somatic mutations present in as few as 12% of CTCs. We found in CTCs a total of 2,766 somatic single-nucleotide variants and 543 indels and multi-base substitutions, 23 of which altered amino acid sequences. Another 16,961 somatic single nucleotide variant and 8,408 indels and multi-base substitutions, 77 of which were nonsynonymous, were detected with varying degrees of prevalence across the 34 CTCs. On the basis of our whole genome data of mutations found in all CTCs, we identified driver mutations and the tissue of origin of these cells, suggesting personalized combination therapies beyond the scope of most gene panels. Taken together, our results show how advanced WGS of CTCs can lead to high-resolution analyses of cancers that can reliably guide personalized therapy. Cancer Res; 77(16); 4530–41. ©2017 AACR.
Neutrophils in cancer: prognostic role and therapeutic strategies
Authors: Alberto Ocana, Cristina Nieto-Jiménez, Atanasio Pandiella, Arnoud J Templeton
Journal: Molecular Cancer (2017)

Expression of high levels of immune cells including neutrophils has been associated with detrimental outcome in several solid tumors and new strategies to decrease their presence and activity are currently under clinical development. Here, we review some of the relevant literature of the role of neutrophils in different stages of the oncogenic process including tumor initiation, growth, proliferation or metastatic spreading and also focus on how neutrophil counts or the neutrophil-to-lymphocyte ratio may be used as a prognostic and predictive biomarker. Strategies to avoid the deleterious effects of neutrophils in cancer and to reduce their activity are discussed. Examples for such strategies include inhibition of CXCR1 and CXCR2 to decrease migration of neutrophils to tumoral areas or the inhibition of granulocyte colony stimulating factor to decrease the amount of neutrophils which has shown efficacy in preclinical models.
Abstract 18886: Predictors for Long-term Clinical Outcomes After Endovascular Treatment in Patients With Critical Limb Ischemia
Authors: Kentaro Jujo, Masashi Nakao, Junichi Yamaguchi, Hisao Otsuki, Kensuke Shimazaki, Kazuho Kamishima, Hiroyuki Arashi, Nobuhisa Hagiwara
Journal: Circulation (2015)

Backgrounds: Critical limb ischemia (CLI) is a severe clinical presentation of patients with peripheral artery disease, and their limb salvage and survival rates are extremely poor. However, there is still only limited evidence from observational studies for contemporary outcomes in CLI patients who underwent endovascular treatment (EVT) including both above and below the knee lesion. Therefore, this study aimed to evaluate the prognostic and predictive factors for patients with CLI who underwent EVT. Methods: Cumulative total number of 192 patients with CLI who underwent EVT between March 2009 and April 2014 was prospectively enrolled. After the exclusion of patients who were lost to follow-up within 6 months, 175 patients were retrospectively analyzed for clinical and angiographic parameters. The primary endpoints of this study were all-cause death and major amputation above the ankle joint. Results: The study population was typically elderly (average age: 68 year-old) and 76% male with a normal body mass index (BMI: 23 kg/m2) and diverse comorbidities, including 34% diabetes and 72% maintenance hemodialysis. Target lesions consisted of 23% aortoiliac, 56% femoropopliteal and 67% below-the-knee arteries, including 37% isolated below-the-knee lesion. Median follow-up period was 23.9 months. Survival rate and major amputation free rate at 1-year were 87% and 95%, respectively (Figure). Multivariate analysis elucidated that low BMI and cerebrovascular disease were independent predictors for all-cause mortality (Table 1). Interestingly, infection was the leading cause of death (23 patients (46%), and main focus of infection was lower extremities (15 patients (30%)). As for major limb amputation, current smoking was the only independent predictor (Table 2). Conclusion: This study demonstrates that low BMI and cerebrovascular disease predict all-cause mortality, and current smoking does major amputation after EVT in patients with CLI.
変異CCL2蛋白質被覆はマウス連続ポリエチレン注入モデルにおける摩耗粒子誘発骨量減少を軽減する【Powered by NICT】
Authors: Nabeshima Akira, Pajarinen Jukka, Lin Tzu-hua, Jiang Xinyi, Gibon Emmanuel, A Cordova Luis, Loi Florence, Lu Laura, Jaemsen Eemeli, Egashira Kensuke, Yang Fan, Yao Zhenyu, B Goodman Stuart
Journal: Biomaterials (2017)
FRI0751-HPR Safety profile of tofacitinib in patients with rheumatoid arthritis - a real world experience with good results
Authors: A Malpica, P Santos-Moreno, K Mendez, D Buitrago-Garcia
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Tofacinitib is an oral Janus Kinase for the treatment for rheumatoid arthritis (RA). The efficacy and safety of tofacitinib in monotherapy or in combination with other DMARDs has been demonstrated in clinical trials. However previous studies had report hematological changes and infections associated to the use of this medication (1, 2); in the European Union (EU) Tofacitinib is an investigational medicine and has not been approved for use because concernings regarding its safety. <h3>Objectives</h3> We aim to describe the safety profile of Tofacitinib in patients with RA in in a real-life setting in Bogotá, Colombia. <h3>Methods</h3> During 2015- 2016 we followed patients from a RA specialized center in Colombia receiving Tofacinitib. Patients were treated with therapeutic goals T2T and a multidisciplinary approach. Adverse events were classified according the Common Terminology Criteria for Adverse Events (CTCAE) of the World Health Organization. Descriptive epidemiology for continuous variables, measure of central tendency and dispersion for qualitative and categorical variables through percentages and averages were calculated. <h3>Results</h3> We included 56 patients receiving tofacitinib, 80% were woman, 20% men. Mean age was 60±11 years. The mean time with RA was 17 months ± 12. 70% of patients had comorbidities; the most frequent comorbidity was hypertension 30%, followed by osteoporosis 25%, 7.5% Sjogren9s syndrome, 7.5% diabetes mellitus among others. 70% of patients received some Anti-TNF drugs before using Tofacitinib; average time receiving tofacitinib was 33±32 weeks, mean DAS28 was 3.7±1.6. Regarding safety profile 10 of 56 patients presented any adverse event. 5 were mild, 4 moderate and 1 severe (1.7%). Diarrhea 1, Infections 1, Abdominal discomfort 3, Mouth papules 1, Rash 1, Sinusitis 1, Headache 1, Folliculitis 1 and Pancreatitis 1. <h3>Conclusions</h3> Tofacitinib is a safe and effective medication for patients with AR; regarding safety the proportion of patients with any AE is lower compared to previous studies, but the type of events were similar to clinical trials (1); none of our patients presented hematological changes; none of our patients presented Herpes Zoster infection. <h3>References</h3> Wollenhaupt J, Silverfield J, Lee EB, Curtis JR, Wood SP, Soma K, et al. Safety and efficacy of tofacitinib, an oral janus kinase inhibitor, for the treatment of rheumatoid arthritis in open-label, longterm extension studies. The Journal of rheumatology. 2014;41(5):837–52. He Y, Wong AY, Chan EW, Lau WC, Man KK, Chui CS, et al. Efficacy and safety of tofacitinib in the treatment of rheumatoid arthritis: a systematic review and meta-analysis. BMC musculoskeletal disorders. 2013;14:298. <h3>Disclosure of Interest</h3> None declared
Interim safety analysis of a phase III trial with 5-FU, oxaliplatin, and docetaxel (FLOT) versus epirubicin, cisplatin, and 5-FU (ECF) in patients with locally advanced, resectable gastric/oesophagogastric junction (OGJ) cancer: The AIO-sto-0210 FLOT4 study.
Authors: Claudia Pauligk, Johannes Meiler, Ralf Dieter Hofheinz, Hans-Georg Kopp, Frank Mayer, Harald Schmalenberg, Kim Luley, Georg Martin Haag, Wolff H. Schmiegel, Nils Homann, Stephan Probst, Michael Koenigsmann, Nicole Prasnikar, Jorg Trojan, Matthias Egger, Rolf Mahlberg, Michael Heike, Andrea Tannapfel, Elke Jäger, Salah-Eddin Al-Batran
Journal: Journal of Clinical Oncology (2013)

4079 Background: Perioperative ECF is a standard treatment for localized gastric/OGJ adenocarcinoma. However, 5-year survival rate remains below 40%. The FLOT regimen is an effective combination with pathologic response rates in the 15% range. This phase III study compares both regimens in resectable stages. Methods: Pts are stratified by different baseline criteria and randomized to either 3 + 3 perioperative cycles of ECF (epirubicin 50 mg/m 2 , d1; cisplatin 60 mg/m², d1; 5-FU 200 mg/m², d1-d21, qd21) or 4 + 4 cycles of perioperative FLOT (docetaxel 50mg/m 2 , d1; 5-FU 2600 mg/m², d1; leucovorin 200 mg/m², d1; oxaliplatin 85 mg/m², d1, qd14). 5-FU can be replaced by capecitabine in the ECF-arm (ECX). Central pathology is performed. This is a preplanned safety analysis after 300 patients. Results: The ongoing studyhas enrolled 380 of planned 590 pts, so far. 305 pts were included in this analysis. Median age is 62 yrs; 78% of pts are male. The primaries were gastric in 44.9%, OGJ in 50.4% and not evaluable/documented in 4.7% of pts. 281 pts were eligible for safety analyses. Median no. of preoperative cycles was 3 and 4 with ECF/ECX and FLOT, respectively, 35.9% vs. 44.6% of pts (ECF/ECX vs. FLOT) started postoperative chemotherapy (ct) and 22.5% vs 33.1% received all planned cycles. Grade 3/4 neutropenia was observed in 28.0% of ECF/ECX and 45.3% of FLOT pts (p=.0026). Thromboembolic events occurred in 14.1% vs. 5.8% in pts with ECF/ECX vs. FLOT (p=.027). Serious adverse events occurred in 52.1% vs. 47.5% of pts with ECF/ECX vs. FLOT (p=.48). Preoperative delay/interruptions of ct were observed in 71.1% vs. 56.8% of pts with ECF/ECX vs. FLOT (p=.013). Dose modifications of preoperative ct were performed in 27.5% vs. 20.1% of treatment cycles with ECF/ECX vs. FLOT, respectively. 197 pts have undergone surgery so far. Severe surgical morbidity was similar in both arms (ECF/ECX, 19.8%; FLOT, 16.8%). Surgical mortality was observed in 4 and 2 pts with ECF/ECX and FLOT. Toxic deaths were observed in 1 pt each. Conclusions: Perioperative FLOT is feasible and safe. Clinical trial information: NCT01216644.
Effect of Foster Nursing on the Response of Mice to Estrogens
Authors: Michael B. Shimkin, Howard B. Andervont
Journal: JNCI Journal of the National Cancer Institute (1941)

Journal Article Effect of Foster Nursing on the Response of Mice to Estrogens Get access Michael B. Shimkin, Michael B. Shimkin assistant surgeon National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar Howard B. Andervont Howard B. Andervont principal biologist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 1, Issue 5, April 1941, Pages 599–605, https://doi.org/10.1093/jnci/1.5.599 Published: 01 April 1941
New Horizons for Precision Medicine in Biliary Tract Cancers
Authors: Juan W. Valle, Angela Lamarca, Lipika Goyal, Jorge Barriuso, Andrew X. Zhu
Journal: Cancer Discovery (2017)

Abstract Biliary tract cancers (BTC), including cholangiocarcinoma and gallbladder cancer, are poor-prognosis and low-incidence cancers, although the incidence of intrahepatic cholangiocarcinoma is rising. A minority of patients present with resectable disease but relapse rates are high; benefit from adjuvant capecitabine chemotherapy has been demonstrated. Cisplatin/gemcitabine combination chemotherapy has emerged as the reference first-line treatment regimen; there is no standard second-line therapy. Selected patients may be suitable for liver-directed therapy (e.g., radioembolization or external beam radiation), pending confirmation of benefit in randomized studies. Initial trials targeting the epithelial growth factor receptor and angiogenesis pathways have failed to deliver new treatments. Emerging data from next-generation sequencing analyses have identified actionable mutations (e.g., FGFR fusion rearrangements and IDH1 and IDH2 mutations), with several targeted drugs entering clinical development with encouraging results. The role of systemic therapies, including targeted therapies and immunotherapy for BTC, is rapidly evolving and is the subject of this review. Significance: The authors address genetic drivers and molecular biology from a translational perspective, in an intent to offer a clear view of the recent past, present, and future of BTC. The review describes a state-of-the-art update of the current status and future directions of research and therapy in advanced BTC. Cancer Discov; 7(9); 943–62. ©2017 AACR.
Review: Metabolic Control of Immune System Activation in Rheumatic Diseases
Authors: Andras Perl
Journal: Arthritis & Rheumatology (2017)

Metabolic pathways mediate lineage specification within the immune system through the regulation of glucose utilization, a process that generates energy in the form of ATP and synthesis of amino acids, nucleotides, and lipids to enable cell growth, proliferation, and survival. CD4+ T cells, a proinflammatory cell subset, preferentially produce ATP through glycolysis, whereas cells with an antiinflammatory lineage, such as memory and regulatory T cells, favor mitochondrial ATP generation. In conditions of metabolic stress or a shortage of nutrients, cells rely on autophagy to secure amino acids and other substrates, while survival depends on the sparing of mitochondria and maintenance of a reducing environment. The pentose phosphate pathway acts as a key gatekeeper of inflammation by supplying ribose‐5‐phosphate for cell proliferation and NADPH for antioxidant defenses. Increased lysosomal catabolism, accumulation of branched amino acids, glutamine, kynurenine, and histidine, and depletion of glutathione and cysteine activate the mechanistic target of rapamycin (mTOR), an arbiter of lineage development within the innate and adaptive immune systems. Mapping the impact of susceptibility genes to metabolic pathways allows for better understanding and therapeutic targeting of disease‐specific expansion of proinflammatory cells. Therapeutic approaches aimed at glutathione depletion and mTOR pathway activation appear to be safe and effective for treating lupus, while an opposing intervention may be of benefit in rheumatoid arthritis. Environmental sources of origin for metabolites within immune cells may include microbiota and plants. Thus, a better understanding of the pathways of immunometabolism could provide new insights into the pathogenesis and treatment of the rheumatic diseases.
Effect of Carcinogens on Small Free-Living Organisms I. Eberthella Typhi
Authors: R. R. Spencer, M. B. Melroy
Journal: JNCI Journal of the National Cancer Institute (1940)

Effect of Carcinogens on Small Free-Living Organisms I. Eberthella Typhi Get access R. R. Spencer, R. R. Spencer assistant chief National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar M. B. Melroy M. B. Melroy assistant bacteriologist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 1, Issue 2, October 1940, Pages 129–134, https://doi.org/10.1093/jnci/1.2.129 Published: 01 October 1940
THU0329 Budd-chiari syndrome in behÇet's disease: a retrospective multicenter study
Authors: L Akyol, B Toz, Ö Bayındır, O Zengin, D Üsküdar Cansu, M Yiğit, G Çetin Yıldırım, A Omma, A Erden, O Küçükşahin, MS Altuner, BS Çorba, AU Ünal, H Küçük, A Küçük, A Balkarlı, E Gönüllü, AN Tufan, S Üreyen Bakırcı, S Öner Yılmaz, S Kobak, A Yazıcı, M Özgen, A Şahin, SS Koca, B Erer, A Gül, K Aksu, G Keser, AM Onat, B Kısacık, T Kaşifoğlu, A Çefle, U Kalyoncu, M Sayarlıoğlu
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The aim of this study was to determine the demographic, clinical, laboratory and management characteristics along with the clinical course of Budd-Chiari syndrome (BCS) associated with Behçet9s disease (BD). <h3>Methods</h3> Sixty patients with BD with BCS (40 male, 20 female) were identified in 23 rheumatology centers (Group I). A total of 169 consecutive patients (100 male, 69 female) with BD who did not have clinically apparent BCS during the follow-up were evaluated as the control group (Group II). <h3>Results</h3> Comparison of the demographic and clinical findings between the Group I and the Group II were as follows: The mean age of disease onset was 23.1 +/- 6.7 years vs. 26.8±0.6 years (p=0.013), mean age at diagnosis was 27.2±0.9 vs. 30.4±0.6 years (p=0.008), arthritis was 10% vs. 28.4% (p=0.002), papulopustular skin lesion was 48.3% vs 69.2% (p=0.003), central nervous system (CNS) involvement 10% vs. 3% (p=0.03), cardiac involvement was 16.7% vs. 2.4% (p&lt;0.001), superficial thrombophlebitis was 23.3% vs. 4.7% (p&lt;0.001), and deep vein thrombosis was 58.3% vs. 15.4% (p&lt;0.01). On diagnosis 50% of BD patients with BCS were classified as Child-Pugh A. Inferior vena cava obstruction was observed in 38.3% and portal vein thrombosis was seen in 3.3% of the patients with BCS. Mortality in BCS patients with BD was 18.3%. BCS related treatment after diagnosis in patients with BD were as follows: 71.7% of patients were treated with monthly cyclophosphamide intravenous pulses, 53.3% received intravenous pulse corticosteroids, 55.9% used azathioprine, 54.2% had warfarine treatment, and 50.8% were treated with low molecular weight heparin. <h3>Conclusions</h3> This study shows a higher frequency of cardiac and CNS involvement, superficial thrombophlebitis, papulopustular skin lesion, deep vein thrombosis in BD patients with BCS. Arthritis was observed less common in BD patients with BCS. The mean age onset was lower in patients with BCS. Medical treatment with immunosuppressive agents and anticoagulation appears to be the treatment of choice in BD patients with BCS. The majority of the patients with BCS were Child–Pugh class A on diagnosis. The inferior vena cava is frequently involved and, often associated with deep vein thrombosis and cardiac involvement. <h3>Disclosure of Interest</h3> None declared