tbuckley/cabot-search huggingface dataset:
Strategies for Optimizing the Soft Tissue Seal around Osseointegrated Implants
Authors: Mohamed‐Nur Abdallah, Zahi Badran, Ovidiu Ciobanu, Nader Hamdan, Faleh Tamimi
Journal: Advanced Healthcare Materials (2017)

Abstract Percutaneous and permucosal devices such as catheters, infusion pumps, orthopedic, and dental implants are commonly used in medical treatments. However, these useful devices breach the soft tissue barrier that protects the body from the outer environment, and thus increase bacterial infections resulting in morbidity and mortality. Such associated infections can be prevented if these devices are effectively integrated with the surrounding soft tissue, and thus creating a strong seal from the surrounding environment. However, so far, there are no percutaneous/permucosal medical devices able to prevent infection by achieving strong integration at the soft tissue–device interface. This review gives an insight into the current status of research into soft tissue–implant interface and the challenges associated with these interfaces. Biological soft/hard tissue interfaces may provide insights toward engineering better soft tissue interfaces around percutaneous devices. In this review, focus is put on the history and current findings as well as recent progress of the strategies aiming to develop a strong soft tissue seal around osseointegrated implants, such as orthopedic and dental implants.
ASTRIS: A real world treatment study of osimertinib in patients (pts) with EGFR T790M positive non-small cell lung cancer (NSCLC).
Authors: Filippo De Marinis, Byoung Chul Cho, Dong-Wan Kim, Sang-We Kim, Maximilian J. Hochmair, Giulio Metro, Johan F. Vansteenkiste, David Vicente, Benjamin J. Solomon, Parneet K. Cheema, Helano C. Freitas, Mariano Provencio, Yuh-Min Chen, Yi-Long Wu, Alvin Milner, James R. Rigas
Journal: Journal of Clinical Oncology (2017)

9036 Background: Osimertinib is an oral, irreversible, central nervous system (CNS) active EGFR tyrosine kinase inhibitor (TKI) selective for both EGFR-TKI sensitizing and T790M resistance mutations. We report results from the first predefined interim analysis of the ongoing ASTRIS study (NCT02474355). Methods: Pts received osimertinib 80 mg once daily. Eligible pts had Stage IIIB-IV NSCLC harbouring a T790M mutation determined by local validated molecular test (not restricted by sample type), received prior EGFR-TKI therapy, WHO performance status (PS) 0−2, acceptable organ and bone marrow function and no history of interstitial lung disease (ILD) or QTc prolongation. Asymptomatic, stable CNS metastases were permitted. The primary efficacy outcome was overall survival; other outcomes included investigator-assessed response rate (RR), progression-free survival and time to treatment discontinuation. Safety data are also reported. Results: From study start (18 Sept 2015) to data cut-off (DCO; 3 Nov 2016), 1217 pts received osimertinib from 120 sites with a median follow-up of 4.1 mths ( &lt; 1−14 mths), median age 64 yrs (27–92 yrs), 67% female, 61% White, 37% Asian, 87% WHO PS 0/1, 44% prior chemotherapy, 45% prior radiotherapy. All pts tested positive for T790M, identified from tissue in 682 pts (56%), plasma ctDNA in 433 pts (36%) and from other specimens in 102 pts (8%). At DCO, 317 pts (26%) had discontinued treatment, 900 pts (74%) were ongoing, median duration of exposure 3.8 mths ( &lt; 1–13.2 mths), 168 pts (14%) had disease progression and 156 pts (13%) had died. In pts evaluable for response, the investigator-assessed RR was 64% (569/886; 95% CI 61, 67). Adverse events (AEs) leading to dose modification and treatment discontinuation were reported in 122 (10%) and 54 pts (4%), respectively. Serious AEs were reported in 165 pts (14%) and AEs leading to death in 30 pts (2%). ILD/pneumonitis-like events were reported in 25 pts (2%), and QTc prolongation in 9 pts (1%). Conclusions: ASTRIS, the largest reported clinical study of osimertinib in T790M-positive NSCLC, demonstrates clinical activity similar to that observed in the osimertinib clinical trial program with no new safety signals. Clinical trial information: NCT02474355.
SIRT2 Acts as a Cardioprotective Deacetylase in Pathological Cardiac Hypertrophy
Authors: Xiaoqiang Tang, Xiao-Feng Chen, Nan-Yu Wang, Xiao-Man Wang, Shu-Ting Liang, Wei Zheng, Yun-Biao Lu, Xiang Zhao, De-Long Hao, Zhu-Qin Zhang, Ming-Hui Zou, De-Pei Liu, Hou-Zao Chen
Journal: Circulation (2017)

Pathological cardiac hypertrophy induced by stresses such as aging and neurohumoral activation is an independent risk factor for heart failure and is considered a target for the treatment of heart failure. However, the mechanisms underlying pathological cardiac hypertrophy remain largely unknown. We aimed to investigate the roles of SIRT2 in aging-related and angiotensin II (Ang II)-induced pathological cardiac hypertrophy.Male C57BL/6J wild-type and Sirt2 knockout mice were subjected to the investigation of aging-related cardiac hypertrophy. Cardiac hypertrophy was also induced by Ang II (1.3 mg/kg/d for 4 weeks) in male C57BL/6J Sirt2 knockout mice, cardiac-specific SIRT2 transgenic (SIRT2-Tg) mice, and their respective littermates (8 to ≈12 weeks old). Metformin (200 mg/kg/d) was used to treat wild-type and Sirt2 knockout mice infused with Ang II. Cardiac hypertrophy, fibrosis, and cardiac function were examined in these mice.SIRT2 protein expression levels were downregulated in hypertrophic hearts from mice. Sirt2 knockout markedly exaggerated cardiac hypertrophy and fibrosis and decreased cardiac ejection fraction and fractional shortening in aged (24-month-old) mice and Ang II-infused mice. Conversely, cardiac-specific SIRT2 overexpression protected the hearts against Ang II-induced cardiac hypertrophy and fibrosis and rescued cardiac function. Mechanistically, SIRT2 maintained the activity of AMP-activated protein kinase (AMPK) in aged and Ang II-induced hypertrophic hearts in vivo as well as in cardiomyocytes in vitro. We identified the liver kinase B1 (LKB1), the major upstream kinase of AMPK, as the direct target of SIRT2. SIRT2 bound to LKB1 and deacetylated it at lysine 48, which promoted the phosphorylation of LKB1 and the subsequent activation of LKB1-AMPK signaling. Remarkably, the loss of SIRT2 blunted the response of AMPK to metformin treatment in mice infused with Ang II and repressed the metformin-mediated reduction of cardiac hypertrophy and protection of cardiac function.SIRT2 promotes AMPK activation by deacetylating the kinase LKB1. Loss of SIRT2 reduces AMPK activation, promotes aging-related and Ang II-induced cardiac hypertrophy, and blunts metformin-mediated cardioprotective effects. These findings indicate that SIRT2 will be a potential target for therapeutic interventions in aging- and stress-induced cardiac hypertrophy.
MicroRNA mediated regulation of TGF-beta signaling leads to stem cell alterations in myelodysplastic syndromes
Authors: T D Bhagat, L Zhou, L Sokol, I Mantzaris, S Bhattacharyya, Gordon Sak., Y Yu, K Gundabolu, S Nischal, R Polineni, C Schinke, G Chrysofakis, A Wickrema, A Pellagatti, J Boultwood, U Steidl, G Liu, A F List, M Bitzer, A Verma
Journal: Cancer Research (2014)
Mapping unmet supportive care needs, quality-of-life perceptions and current symptoms in cancer survivors across the Asia-Pacific region: results from the International STEP Study
Authors: A. Molassiotis, P. Yates, Q. Li, W.K.W. So, K. Pongthavornkamol, P. Pittayapan, H. Komatsu, M. Thandar, M. Yi, S. Titus Chacko, V. Lopez, J. Butcon, D. Wyld, R.J. Chan, Melissa Doolan, Maria Estrella Litam, Rubiliza Onofre, Conchitina Lluch, Rosebe Nacion, Maria Luisa Ombao, Zaw Wai Soe, Theingi Myint, Emily Ang, Harue Arao, Kaori Yagasaki, Vinitha Ravindran, Roselin V. Rhenius, Amalorpavamari Lucas, Lillian Percy Kujur, Abijah Princy, Kai-chow Choi, Yin-ping Choy, Yan-pui Lee, Chun-yip Shiu, Yinghua Xu
Journal: Annals of Oncology (2017)
Activity of cediranib in alveolar soft part sarcoma (ASPS) confirmed by CASPS (cediranib in ASPS), an international, randomised phase II trial (C2130/A12118).
Authors: Ian Robert Judson, James P Morden, Michael Gordon Leahy, Vivek Bhadri, Quentin Campbell-Hewson, Ricardo Cubedo, Adam Dangoor, Ivo M. Hennig, Warren Lance Joubert, Sarah Kernaghan, Antonio Lopez-Pousa, Beatrice M. Seddon, Claire Snowdon, Martin Tatersall, Christy Toms, Javier Martinez-Trufero, Judith Bliss
Journal: Journal of Clinical Oncology (2017)

11004 Background: ASPS is a rare disease (0.5-1% of soft tissue sarcomas) mainly affecting young people. It is unresponsive to conventional chemotherapy. Cediranib (C), an inhibitor of vascular endothelial growth factor receptors and other receptor tyrosine kinases, has shown significant activity in ASPS in single arm phase II trials. CASPS (NCT01337401) was designed to permit discrimination between the impact of cediranib and the often intrinsically indolent nature of the disease. Methods: CASPS compared C (30mg od) with placebo (P) in a 2:1 double blind randomisation in patients (pts) age ≥16 years with metastatic ASPS progressive in the previous 6 months. Pts were unblinded at week 24, or at progression if sooner, when those on P started C. The primary endpoint of percentage change in the sum of target marker lesions (TML sum ) between baseline and week 24 (or progression if sooner) was compared between groups by Mann-Whitney test. Secondary endpoints were progression-free survival (PFS), week 24 response rate and best response (RECIST v1.1), safety/tolerability and overall survival (OS). One-sided p-values and two-sided 90% confidence intervals are reported. Results: 48 pts were recruited between 07/2011 and 07/2016 from 12 centres (UK, Australia &amp; Spain). 52% of pts were female, median age was 31. Most common grade ≥3 adverse events on C were hypertension (23%), diarrhoea (14%) and fatigue (9%). In the evaluable population (N = 44) median change in TML sum on C was minus 8.3% (IQR minus 26.2% to +5.9%); versus P: +13.4% (IQR minus 0.6% to +21.3%), p = 0.0013. Best response by week 24 was partial response for 6/28 (21%) C pts compared with 0/16 on P (p = 0.053) and stable disease for an additional 19/28 (68%) on C and 12/16 (75%) on P. The PFS HR (C versus P) was 0.54 (90% CI 0.30-0.97, p = 0.041), median PFS: 10.8 mths on C versus 3.7 mths on P, OS at 12 mths was C: 96%; P: 64.3%. Conclusions: CASPS, the largest randomised trial to date in this disease, confirms the activity of C in ASPS, showing a significant reduction in tumour burden and improvement in PFS. Tumour tissue and serial blood samples will subsequently be investigated to identify potential predictive and prognostic biomarkers. Clinical trial information: NCT01337401.
The Future of the Neurologic Examination
Authors: Michael J. Aminoff
Journal: JAMA Neurology (2017)

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 Neurology 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 Neurology journal
Immuno-thermal ablations – boosting the anticancer immune response
Authors: Ryan Slovak, Johannes M. Ludwig, Scott N. Gettinger, Roy S. Herbst, Hyun S. Kim
Journal: Journal for ImmunoTherapy of Cancer (2017)

The use of immunomodulation to treat malignancies has seen a recent explosion in interest. The therapeutic appeal of these treatments is far reaching, and many new applications continue to evolve. In particular, immune modulating drugs have the potential to enhance the systemic anticancer immune effects induced by locoregional thermal ablation. The immune responses induced by ablation monotherapy are well documented, but independently they tend to be incapable of evoking a robust antitumor response. By adding immunomodulators to traditional ablative techniques, several researchers have sought to amplify the induced immune response and trigger systemic antitumor activity. This paper summarizes the work done in animal models to investigate the immune effects induced by the combination of ablative therapy and immunomodulation. Combination therapy with radiofrequency ablation, cryoablation, and microwave ablation are all reviewed, and special attention has been paid to the addition of checkpoint blockades.
Endoscopic negative-pressure therapy for duodenal leakage using new open-pore film and polyurethane foam drains with the pull-through technique
Authors: Gunnar Loske, Marc Liedke, Erik Schlöricke, Thomas Herrmann, Frank Rucktaeschel
Journal: Endoscopy (2017)

Few reports have described the use of endoscopic vacuum therapy (EVT) for duodenal defects [1] [2] [3] [4]. We treated a complicated duodenal leak with EVT using the pull-through technique with a new type of open-pore polyurethane-foam drain (OPD) [5] and a novel type of open-pore film drain (OFD).
FGF19 Protects Hepatocellular Carcinoma Cells against Endoplasmic Reticulum Stress via Activation of FGFR4–GSK3β–Nrf2 Signaling
Authors: Yong Teng, Huakan Zhao, Lixia Gao, Wenfa Zhang, Austin Y. Shull, Chloe Shay
Journal: Cancer Research (2017)

Abstract The tumor microenvironment induces endoplasmic reticulum (ER) stress in tumor cells, an event that can promote progression, but it is unknown how tumor cells adapt to this stress. In this study, we show that the fibroblast growth factor FGF19, a gene frequently amplified in hepatocellular carcinoma (HCC), facilitates a survival response to ER stress. Levels of FGF19 expression were increased in stressed HCC cells in culture and in a mouse xenograft model. Induction of ER stress required the transcription factor ATF4, which directly bound the FGF19 promoter. In cells where ER stress was induced, FGF19 overexpression promoted HCC cell survival and increased resistance to apoptosis, whereas FGF19 silencing counteracted these effects. Mechanistic investigations implicated glycogen synthase kinase-3β (GSK3β) in regulating nuclear accumulation of the stress-regulated transcription factor Nrf2 activated by FGF19. Our findings show how FGF19 provides a cytoprotective role against ER stress by activating a FGFR4–GSK3β–Nrf2 signaling cascade, with implications for targeting this signaling node as a candidate therapeutic regimen for HCC management. Cancer Res; 77(22); 6215–25. ©2017 AACR.
Abstract 383: 17 beta-Estradiol Enhances Mitochondrial Function of Cerebral Arteries From Ovariectomized Female Rats
Authors: Ibolya Rutkai, Somhrita Dutta, Korey A Walter, Prasad V Katakam, David W Busija
Journal: Circulation Research (2015)

Previous studies have provided indirect evidence that circulating sex hormones alter the function of the cerebral circulation perhaps via effects on mitochondrial dynamics. However, effects of estrogen on mitochondrial respiration have never been directly examined. We have previously observed a difference in the mitochondrial function of cerebral arteries from male and female rats but the exact mechanisms are not clear. We tested the hypothesis that mitochondrial respiration in isolated cerebral arteries from ovariectomized (OVX) Sprague Dawley rats treated with a 21 d release, 0.5 mg of 17 β-estradiol pellet (OVX+E) was enhanced compared with arteries from placebo treated OVX rats. The Seahorse Bioscience XFe24 system was used to measure mitochondrial oxygen consumption rate (pM/min/μg protein) in cerebral arteries. Western blot was used to investigate the arterial expression of proteins. Radioimmunoassay was used to measure serum estradiol level. Treatment with 17 β-estradiol resulted in a higher serum estradiol level (146.9±18.16 pg/ml) and uterus weight (0.15±0.0058 g) in the OVX+E compared with the OVX (14.7±1.2 pg/ml, 0.07±0.003, respectively; p&lt;0.05). The components of mitochondrial respiration in pM/min/μg protein including basal respiration (147±9), ATP production (44±4), proton leak (102±7), and maximal respiration (212±13) were elevated in OVX+E compared with OVX (105±13, 21±4, 50±6, 138±10, respectively; p&lt;0.05). Expression of the mitochondrial DNA encoded Complexes I and III, the nuclear DNA encoded Complexes II, IV, V, and the voltage-dependent anion channel protein were similar in all groups. However, the ratios of phosphorylated endothelial and neuronal nitric oxide (NO) synthase normalized to total protein were significantly (p&lt;0.05) elevated in the OVX+E (1.43±0.06, 1.15±0.2, respectively) compared with OVX group (0.92±0.06, 0.53±0.19, respectively). Our findings provide direct evidence for sex-specific differences in mitochondrial function on freshly isolated cerebral arteries. Thus, estradiol replacement enhances the efficacy of the oxidative phosphorylation resulting in an increased mitochondrial respiration which is not due to increased mitochondrial protein expression but may be due to enhanced NO.
The combined use of tigecycline with high-dose colistin might not be associated with higher survival in critically ill patients with bacteraemia due to carbapenem-resistant Acinetobacter baumannii
Authors: T. Amat, A. Gutiérrez-Pizarraya, I. Machuca, I. Gracia-Ahufinger, E. Pérez-Nadales, Á. Torre-Giménez, J. Garnacho-Montero, J.M. Cisneros, J. Torre-Cisneros
Journal: Clinical Microbiology and Infection (2017)
Atopic eczema and allergic rhinitis show a dichotomic pattern of IgE-autoreactivity against skin, lung and intestinal epithelium
Authors: T. Seher, H. Beck, J. Mayer, K. Brockow, C. Traidl-Hoffmann, J. Ring, H. Behrendt, M. Ollert, Jan Gutermuth, C Schmidt-Weber
Journal: Allergy (2012)
Orexigenic and cytoprotective effects of a novel adenosine-enriched peptide nucleic acid compound: Implications for clinical application
Authors: J. T. D’Olimpio, S. Elliston, M. Dediego, R. Sodum
Journal: Journal of Clinical Oncology (2007)

14154 Background: There is a major unmet need for new non-toxic orexigenic and cytoprotective agents that can ameliorate intractable symptoms in cancer such as anorexia, poor wound healing/ulcerations and poor QoL. Underlying causes of these clinical problems include excessive inflammatory/cytokine responses to either treatment related or tumor related processes, or to both at once. AVR118, a novel remarkably non-toxic peptide/nucleic acid formulation has been shown in many anecdotal reports and in small clinical trials, to stimulate appetite, improve fatigue, and assist in more rapidly reversing toxic side effects of chemotherapy, radiation and interferon therapy. It has now been re-characterized to better explain these multiple effects. It binds to adenosine receptors in vitro and increases cAMP release in HEK293 cell lines expressing A2 receptors, mechanistically involving targeted receptor binding, most likely in the gut and in the functional pathway of orexin A. Methodologies: HPLC, co-chromatography with standards, UV and mass spectrometry. Receptor binding/functional assays in vitro, animal models for anti-inflammatory and wound healing studies. Results: AVR 118 consists of a mix of 14 nucleoside derivatives, including available adenosine at a concentration of 2.1mM in stable solution. Also present is a complex aggregate of peptides showing high proline and tyrosine content. AVR 118 binds to adenosine receptors in vitro and increases cAMP release in HEK293 cell lines containing A2 receptors and enhances smooth muscle relaxation mediated by A2 and others such as NK2 and NTS1 in vitro. AVR 118 shows 20% enhancement of epithelialization when compared to saline controls in a controlled porcine wound healing model. Conclusions: AVR 118 may prove to play a major role in palliation of anorexia symptoms associated with serious debilitating diseases such as cancer or AIDS and as adjunctive therapy for these patients. [Table: see text] No significant financial relationships to disclose.
Confirmation of the distinct molecular phenotype of inflammatory breast cancer compared to non-inflammatory breast cancer using Affymetrix-based genome-wide gene expression analysis.
Authors: Steven Van Laere, Ilse Van der Auwera, Gert Van den Eynden, Paul Van Hummelen, Peter van Dam, Eric Van Marck, Peter Vermeulen, Luc Dirix
Journal: Cancer Research (2007)

2958    Purpose:  We have shown with genome-wide gene expression analysis using cDNA microarrays that inflammatory breast cancer (IBC) and non-IBC are distinct biological entities. The purpose of this study was to perform a platform independent confirmation of our previous results using Affymetrix whole genome chips.   Experimental Design:  RNA was extracted from 19 IBC samples and 42 non-stage matched non-IBC samples. RNA was hybridized onto Affymetrix HG U133 Plus 2.0 chips in collaboration with the VIB Microarray Facility. Gene expression data were normalized and genes with present flags in at least 30/61 hybridizations were filtered in. Unsupervised hierarchical clustering and principle component analysis (PCA) was executed. Classification of the IBC/non-IBC data set using the intrinsic gene list (Perou et al, Nature, 2000) and application of an NFkB signature (Loercher et al, Cancer Res, 2004) and different EGFR and/or ErbB2 induced MAPK signatures (Creighton et al, Cancer Res, 2006) by unsupervised hierarchical clustering was performed.   Results:  Unsupervised hierarchical clustering using 26601 genes resulted in the identification of two clusters. A first cluster contained 21 samples from which 15 were IBC samples. A second cluster contained 40 samples from which 36 samples were non-IBC samples (Pearson χ 2 ; p 2 ; p 2 , p Conclusions:  These results confirms our previous observation that IBC is a distinct biologic phenotype, characterized by activation of the transcription factor NFkB, possibly through hyperactivation of MAPK’s downstream of EGFR and/or ErbB2. IBC tumours more often demonstrate characteristics from basal-like and ErbB2-overexpressing breast tumours. The fact that IBC tumours have an accelerated clinical course might be explained by this observation. Our data are being validated at protein level using a TMA constructed from the same breast tumour samples.
Hyaluronic acid-green tea catechin micellar nanocomplexes: Fail-safe cisplatin nanomedicine for the treatment of ovarian cancer without off-target toxicity
Authors: Ki Hyun Bae, Susi Tan, Atsushi Yamashita, Wei Xia Ang, Shu Jun Gao, Shu Wang, Joo Eun Chung, Motoichi Kurisawa
Journal: Biomaterials (2017)