tbuckley/cabot-search huggingface dataset:
Abstract 14861: Dual Mode Regulation of Directional Cell Migration by AMPK Using Two Substrates With Distinct Kinetics
Authors: Yi Yan
Journal: Circulation (2015)

Introduction: Striking feature of the regulation of cell migration by AMP-activated protein kinase (AMPK) activity level is that both suppression and augmentation of AMPK inhibit cell migration. Hypothesis: We have previously revealed that AMPK inhibition perturbs cell migration through the destabilisation of the microtubule cytoskeleton via de-phosphorylation of the microtubule plus-end protein CLIP-170. However, the mechanism for how AMPK activation also perturbs cell migration still remains unknown. Methods and Results: Here we used LC/MS to identify a novel substrate of AMPK: PDZ and LIM domain 5 (PDLIM5) is specifically phosphorylated only when AMPK activity is increased. Vascular smooth muscle cells expressing the phosphomimetic PDLIM5 mutant showed perturbed cell migrations accompanied by enlarged focal adhesions and enhanced stress fibre formation without disturbing the microtubule structures. Interestingly, the phosphorylation of PDLIM5 reduced its affinity for α-actinin, which may mechanistically contribute to actin cytoskeleton reorganisation and consequentially the inhibition of cell migration. Conclusions: We proposed the dual mode model, which regulates the directional cell migration of AMPK using the two substrates CLIP-170 and PDLIM5, with distinct activation kinetics to regulate cell migration separately by sensing the level of AMPK activity between two extremes.
Coherence Through Incongruence—Can Genetic Markers Inform Nosology After All?
Authors: Lexie Wille, Francis J. McMahon
Journal: JAMA Psychiatry (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 Psychiatry 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 Psychiatry journal
Learning curve and competence for volumetric laser endomicroscopy in Barrett’s esophagus using cumulative sum analysis
Authors: Arvind Trindade, Sumant Inamdar, Michael Smith, Lisa Rosen, Dennis Han, Kenneth Chang, Cadman Leggett, Charles Lightdale, Douglas Pleskow, Divyesh Sejpal, Guillermo Tearney, Rebecca Thomas, Michael Wallace
Journal: Endoscopy (2017)

Little is known about the learning curve for image interpretation in volumetric laser endomicroscopy (VLE) in Barrett's esophagus (BE). The goal of this study was to calculate the learning curve, competence of image interpretation, sensitivity, specificity, and accuracy of VLE among novice users.31 novice users viewed 96 VLE images electronically at three academic institutions after a brief training session. There were 24 images of each histologic type: normal gastric cardia, normal esophageal squamous epithelium, non-neoplastic BE, and neoplastic BE. The users were asked to identify the correct tissue type and level of confidence. The cumulative summation (CUSUM) technique was used to construct a learning curve.22 (71 %) of the physicians achieved VLE interpretation competency during their 96-slide review. Half of the physicians achieved competency at 65 images (95 % confidence interval [CI] 45 - 85). There was a statistically significant association between confidence in diagnosis and selecting the correct histologic tissue type (P < 0.001). The median accuracy for esophageal squamous epithelium, normal gastric cardia, non-neoplastic BE, and neoplastic BE was 96 % (95 %CI 95 % - 96 %), 95 % (95 %CI 94 % - 96 %), 90 % (95 %CI 88 % - 91 %), 96 % (95 %CI 95 % - 96 %). The overall accuracy was 95 % (95 %CI 93 % - 95 %).The majority of novice users achieved competence in image interpretation of VLE for BE, using a pre-selected image set, with a favorable learning curve after a brief training session. An electronic review of VLE images, prior to real-time use of VLE, is encouraged.
Efficacy and safety outcomes of recanalisation procedures in patients with acute symptomatic pulmonary embolism: systematic review and network meta-analysis
Authors: David Jimenez, Carlos Martin-Saborido, Alfonso Muriel, Javier Zamora, Raquel Morillo, Deisy Barrios, Frederikus A Klok, Menno V Huisman, Victor Tapson, Roger D Yusen
Journal: Thorax (2017)

Background We aimed to review the efficacy and safety of recanalisation procedures for the treatment of PE. Methods We searched PubMed, the Cochrane Library, EMBASE, EBSCO, Web of Science and CINAHL databases from inception through 31 July 2015 and included randomised clinical trials that compared the effect of a recanalisation procedure versus each other or anticoagulant therapy in patients diagnosed with PE. We used network meta-analysis and multivariate random-effects meta-regression to estimate pooled differences between each intervention and meta-regression to assess the association between trial characteristics and the reported effects of recanalisation procedures versus anticoagulation. Results For all-cause mortality, there were no significant differences in event rates between any of the recanalisation procedures and anticoagulant treatment (full-dose thrombolysis: OR 0.60; 95% CI0.36 to 1.01; low-dose thrombolysis: 0.47; 95% CI 0.14 to 1.59; and catheter-associated thrombolysis: 0.31; 95% CI 0.01 to 7.96). Full-dose thrombolysis increased the risk of major bleeding (2.00; 95% CI 1.06 to 3.78) compared with anticoagulation. Catheter-directed thrombolysis was associated with the lowest probability of dying (surface under the cumulative ranking curve (SUCRA), 0.67), followed by low-dose thrombolysis (SUCRA, 0.66) and full-dose thrombolysis (SUCRA, 0.55). Similarly, low-dose thrombolysis was associated with the lowest probability of major bleeding (SUCRA, 0.61), followed by catheter-directed thrombolysis (SUCRA, 0.54) and full-dose thrombolysis (SUCRA, 0.17). The results were similar in sensitivity analyses based on restricting only to studies in haemodynamically stable patients with PE. Conclusions In the treatment of PE, recanalisation procedures do not seem to offer a clear advantage compared with standard anticoagulation. Low-dose thrombolysis was associated with the lowest probability of dying and bleeding. Trial registration number PROSPERO CRD42015024670.
MiR-31-5p-ACOX1 Axis Enhances Tumorigenic Fitness in Oral Squamous Cell Carcinoma Via the Promigratory Prostaglandin E2
Authors: Yi-Hsuan Lai, Hsuan Liu, Wei-Fan Chiang, Ting-Wen Chen, Lichieh Julie Chu, Jau-Song Yu, Shu-Jen Chen, Hua-Chien Chen, Bertrand Chin-Ming Tan
Journal: Theranostics (2017)

During neoplastic development, a multitude of changes in genome-encoded information are progressively selected to confer growth and survival advantages to tumor cells. microRNAs-mRNAs regulatory networks, given their role as a critical layer of robust gene expression control, are frequently altered in neoplasm. However, whether and how these gene perturbations impact metabolic homeostasis remains largely unresolved. Methods: Through targeted miRNA expression screening, we uncovered an oral squamous cell carcinoma (OSCC)-associated miRNAome, among which miR-31-5p was identified based on extent of up-regulation, functional impact on OSCC cell migration and invasion, and direct regulation of the rate-limiting enzyme in peroxisomal β-oxidation, ACOX1. Results: We further found that both miR-31-5p and ACOX1 underpin, in an antagonistic manner, the overall cellular lipidome profiles as well as the migratory and invasive abilities of OSCC cells. Interestingly, the extracellular levels of prostaglandin E2 (PGE2), a key substrate of ACOX1, were controlled by the miR-31-5p-ACOX1 axis, and were shown to positively influence the extent of cell motility in correlation with metastatic status. The promigratory effect of this metabolite was mediated by an elevation in EP1-ERK-MMP9 signaling. Of note, functional significance of this regulatory pathway was further corroborated by its clinicopathologically-correlated expression in OSCC patient specimens. Conclusions: Collectively, our findings outlined a model whereby misregulated miR-31-5p-ACOX1 axis in tumor alters lipid metabolomes, consequently eliciting an intracellular signaling change to enhance cell motility. Our clinical analysis also unveiled PGE2 as a viable salivary biomarker for prognosticating oral cancer progression, further underscoring the importance of lipid metabolism in tumorigenesis.
Increased Hypovolemia Time Increases Mortality in a Swine Model of Traumatic Pulseless Electrical Activity Cardiac Arrest: A Pilot Study
Authors: Jacqueline Evans, J D Morgan, M Castaneda, S Boudreau, K Canellis, J Rall, A Arana, J K Maddry, K L Anderson
Journal: Circulation (2017)

Introduction: Pulseless Electrical Activity (PEA) is the most common presenting arrhythmia in traumatic arrest. There currently are no well-defined animal models for traumatic PEA arrest. Our objec...
Observations of hepatocellular carcinoma (HCC) management patterns from the global HCC bridge study: First characterization of the full study population.
Authors: Joong-Won Park, Morris Sherman, Massimo Colombo, Lewis R. Roberts, Myron E. Schwartz, Francoise Degos, Pei-Jer Chen, Minshan Chen, Masatoshi Kudo, Philip James Johnson, Baisong Huang, Lucinda S. Orsini
Journal: Journal of Clinical Oncology (2012)

4033 Background: HCC is a major health problem across the world. The global HCC BRIDGE study is the first global, large-scale, observational study to document the real-world experience of HCC patients from diagnosis to death. Methods: This longitudinal cohort study (started March 2009) includes HCC patients newly diagnosed between January 2005 and June 2011 and treated at major medical centers, with data collected retrospectively and prospectively as recorded in patient charts. Full patient enrollment is expected at the end of January 2012. Results: At the time of the first interim analysis (July 2011), 12,442 treated HCC patients were enrolled at 42 sites in Asia (n=8909, 72% [China: n=6295, 71%; Japan: n=295, 3%]), Europe (n=2040, 16%) and North America 1493 (n=1493, 12%). Mean age was 57 years; 82% were male. The predominant risk factor was HBV in Asia (76%) and HCV in Europe (48%), North America (45%) and Japan (69%). Most patients were diagnosed without surveillance (Asia, 82%; Europe, 73%; North America, 69%; Japan, 64%). In Asia, Europe and North America, the predominant BCLC stage at diagnosis was C (48%, 46%, 46%) followed by A (34%, 28%, 26%). First recorded treatments in Asia, Europe and North America were resection (31%, 15%, 21%), transplantation (1%, 3%, 1%), TACE (49%, 30%, 36%), other locoregional therapy (12%, 35%, 23%) and systemic therapy (3%, 10%, 8%). Treatments ever used (2005–2011) in Asia, Europe and North America were resection (33%, 17%, 24%), transplantation (2%, 6%, 12%), TACE (57%, 35%, 48%), other locoregional therapy (20%, 42%, 37%) and systemic therapy (9%, 20%, 21%). These results will be updated with data from the full study population (approx. 19,000 patients), and preliminary survival data will be presented. Conclusions: As the largest study of its type, in 19,000 patients worldwide, the HCC BRIDGE study provides valuable insights into global HCC disease characteristics and patient management. Based on prior analyses, differences in risk factors among regions confirm well-known trends, while other observed differences (e.g., treatment variations) may be related to country- and site-specific practices and patient characteristics.
The effect of nurse-led pain education of patients with painful bone metastases on pain and quality of life: A multicenter randomized trial.
Authors: Jenske I. Geerling, Natasja Raijmakers, Veronique E.M. Mul, Ellen JM de Nijs, Marianne A Oudhof, Gertruida Hendrika de Bock, Alexander De Graeff, Yvette M van der Linden, Anna K.L. Reyners
Journal: Journal of Clinical Oncology (2017)

203 Background: Radiotherapy (RT) is an effective treatment for painful bone metastases, although pain is not always sufficiently controlled. Pain management education may improve patient empowerment and, consequently, reduce pain intensity. The effect of nurse-led education (NLE) in patients undergoing RT for painful bone metastases was investigated as compared to care as usual (CAU). Primary endpoint was pain intensity at 12 weeks, secondary outcome was quality of life (QoL). Methods: In this multicentre, randomised phase 3 study, patients referred for short schedule RT, with uncontrolled pain (a score of ≥5 on a 0-10 numeric rating scale (NRS)), were randomised between NLE or CAU before start of RT. The NLE consisted of a structured interview including assessment of pain knowledge, verbal and written education on all aspects of pain and follow-up phone calls at 1, 4, 8 &amp; 12 weeks to address pain-related questions. Patients in CAU received leaflets on RT, cancer pain and opioid use. Patient characteristics were assessed at baseline. Pain intensity and QoL were evaluated with the Brief Pain Inventory, EORTC QLQ-C15-PAL and EORTC QLQ-BM22 at baseline, and week 1, 4, 8 &amp; 12. Power calculation showed that there were 89 patients per arm needed to detect a 10% difference in number of patients with a NRS &lt; 5 at 12 weeks(1-sided α = 0.05; β 0.8). Results: Between May 2011-April 2016, 354 patients were randomised (176 NLE, 178 CAU), 38 were excluded (30 NRS &lt; 5 at baseline, 7 no short schedule RT, 1 missing informed consent). At twelve weeks, 185 (NLE 95) had completed follow-up (72 stopped filling out questionnaires, 59 died prematurely). Baseline characteristics were similar in both groups; mean age 65 years, 56% men. At week 12, more patients in NLE than in CAU had controlled pain (NRS &lt; 5; respectively 66% and 52%, p = 0.036). Moreover, patients in NLE reached faster a pain score &lt; 5 than patients in CAU (31 versus 54 days respectively, p = 0.026). On all time points, no significant differences in QoL were found between both groups. Conclusions: Controlled pain, i.e. a pain intensity &lt; 5, was reached faster and by more patients with painful bone metastases undergoing RT by the addition of nurse-led pain education. Clinical trial information: NCT01358539.
Will You Be My Mentor?—Four Archetypes to Help Mentees Succeed in Academic Medicine
Authors: Vineet Chopra, Vineet M. Arora, Sanjay Saint
Journal: JAMA Internal Medicine (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 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
Characterization of epitope specificities of reference antibodies used for the quantification of the birch pollen allergen Bet v 1
Authors: S. Brier, M. Le Mignon, K. Jain, C. Lebrun, F. Peurois, C. Kellenberger, V. Bordas‐Le Floch, L. Mascarell, E. Nony, P. Moingeon
Journal: Allergy (2017)

Abstract Background Accurate allergen quantification is needed to document the consistency of allergen extracts used for immunotherapy. Herein, we characterize the epitope specificities of two monoclonal antibodies used in an ELISA for the quantification of the major birch pollen allergen Bet v 1, established as a reference by the BSP 090 European project. Methods The ability of mA bs 5B4 and 6H4 to recognize Bet v 1 isoforms was addressed by immunochromatography. The capacity of each mA b to compete with patients’ IgE for binding to Bet v 1 was measured by ELISA inhibition. Epitope mapping was performed by pepscan analysis, site‐directed mutagenesis, and hydrogen/deuterium exchange‐mass spectrometry. Results The 5B4 epitope corresponds to a peptide sequence (I56‐K68) overlapping with the binding sites of patients’ serum IgEs. Mutation of residues P59, E60, and K65 abolishes 5B4 binding to Bet v 1 and reduces the level of IgE recognition. In contrast, 6H4 recognizes a conformational epitope lying opposite to the 5B4 binding site, involving residues located in segments I44‐K55 and R70‐F79. Substitution of E45 reduces the binding capacity of 6H4, confirming that it is critical for the interaction. Both mA bs interact with &gt;90% of Bet v 1 content present in the birch pollen extract, while displaying a weak cross‐reactivity with other allergens of the PR ‐10 family. Conclusions MA bs 5B4 and 6H4 recognize structurally distinct epitopes present in the vast majority of Bet v 1 isoforms. These results support the relevance as a reference method of the Bet v 1‐specific quantitative ELISA adopted by the European Pharmacopoeia.
Evolution of Alternative Adaptive Immune Systems in Vertebrates
Authors: Thomas Boehm, Masayuki Hirano, Stephen J. Holland, Sabyasachi Das, Michael Schorpp, Max D. Cooper
Journal: Annual Review of Immunology (2017)

Adaptive immunity in jawless fishes is based on antigen recognition by three types of variable lymphocyte receptors (VLRs) composed of variable leucine-rich repeats, which are differentially expressed by two T-like lymphocyte lineages and one B-like lymphocyte lineage. The T-like cells express either VLRAs or VLRCs of yet undefined antigen specificity, whereas the VLRB antibodies secreted by B-like cells bind proteinaceous and carbohydrate antigens. The incomplete VLR germline genes are assembled into functional units by a gene conversion–like mechanism that employs flanking variable leucine-rich repeat sequences as templates in association with lineage-specific expression of cytidine deaminases. B-like cells develop in the hematopoietic typhlosole and kidneys, whereas T-like cells develop in the thymoid, a thymus-equivalent region at the gill fold tips. Thus, the dichotomy between T-like and B-like cells and the presence of dedicated lymphopoietic tissues emerge as ancestral vertebrate features, whereas the somatic diversification of structurally distinct antigen receptor genes evolved independently in jawless and jawed vertebrates.
Correlation of a whole blood RNA assay detecting AR-v7 expression with PSA response in patients with metastatic castration-resistant prostate cancer (mCRPC)
Authors: E. Kwan, S. To, H. Fettke, M. Docanto, L. Martelotto, N. Ng, A. Mant, P. Parente, C. Pezaro, T. Todenhöfer, A. Azad
Journal: Annals of Oncology (2017)
Theories or fragments?
Authors: Nick Chater, Mike Oaksford
Journal: Behavioral and Brain Sciences (2017)

Abstract Lake et al. argue persuasively that modelling human-like intelligence requires flexible, compositional representations in order to embody world knowledge. But human knowledge is too sparse and self-contradictory to be embedded in “intuitive theories.” We argue, instead, that knowledge is grounded in exemplar-based learning and generalization, combined with high flexible generalization, a viewpoint compatible both with non-parametric Bayesian modelling and with sub-symbolic methods such as neural networks.
Inhibitory Effects of Triptolide Nanovehicles on Tumor Growth and Metastases.
Authors: Shanmin Yang, Ying Su, Zhenyu Xiao, Wei Wang, Liang Xu, Paul Okunieff, Lurong Zhang
Journal: Cancer Research (2006)

5459  Triptolide (TPL), a diterpenoid triepoxides-like small molecule purified from Tripterygium wilfordii Hook F., has been used as an anti-tumor and anti-inflammation agent with very promising results from clinical trails. For the better targeting on tumor and the reducing of TPL toxicity, the improvement of deliver formula of TPL is needed. Four forms of TPL Nan vehicles were prepared as follow: 1) TPL-PEG-Lip, which was made by enrapture of TPL in liposome (Lip) with 1,2-Dipalmitoyl-sn-Glycero-3-Phosphoethanolamine-N-[Amino (Polyethylene Glycol) 2000] (H2N-PEG-DPPE); 2) TPL-Fol-PEG-Lip, which utilized the folate to enhance the targeting ability to tumor cells via the over-expressed folate receptors; 3) TPL-Transferrin-Lip, which utilized the transferrin to target tumor cells via transferring receptors; and 4) TPL-hyaluronan (HA)-Lip, which utilized the hyaluronan as ligand for CD44 over-expressed on surface of tumor cells. The effects of different TPL nanovehicles on the tumor cell growth were examined in vitro. The effect of TPL-PEG-Lip or TPL-Fol-PEG-Lip on tumor growth or experimental lung metastasis was tested in vivo.In vitro, when B16 melanoma cells were exposed to the same concentration (5 ng/ml) of TPL, the extent of inhibition rate of proliferation was greater in cells treated with TPL-PEG-Lip, TPL-Fol-PEG-Lip, TPL-Transferrin-Lip and TPL-HA-Lip as compared with parental TPL. Similar results were obtained with 4T1 breast cancer cells treated with TPL nanovehicles. In vivo, the effects of TPL nanovehicles were tested in two models. First, the xenografts of B16 melanoma in C57BL/6 and 4T1 breast cancer model were used. At the same dose of TPL (0.15 mg/kg, three times a week), the mice treated with TPL-PEG-Lip achieved a better tumor inhibition rate than those treated with other nanovehicles and the parental TPL. The TPL-PEG-Lip used at a dose of 0.15 mg/kg/three times a week could have a similar inhibitory effect as TPL used at a dose of 0.25 mg/kg/three times a week. Second, the experimental lung metastasis formed by 4T1 breast cancer cells was used. At the TPL dose of 0.2 mg/kg three times a week, the TPL-PEG-Lip and TPL-Fol-PEG-Lip achieved a similar inhibition effect on lung metastases as parental TPL. The LD50 in BALB/C mice indicated that TPL-Fol-PEG-Lip, TPL-HA-Lip and TPL-PEG-Lip did not have an increased toxicity. These data indicate that the increase of size of TPL and linkage of TPL with targeting molecules might enhance the treatment effect of TPL.