tbuckley/cabot-search huggingface dataset:
Can Diffusion and Perfusion Weighted Imaging predict 1p/19q codeled lower grade gliomas?
Authors: Marica Eoli, Valeria Cuccarini, Rosina Paterra, Mariangela Farinotti, Lucia Cuppini, Alessandra Erbetta, Francesco DI Meco, Graziella Filippini, Gaetano Finocchiaro, Maria Grazia Bruzzone
Journal: Journal of Clinical Oncology (2015)

2056 Background: Several factors influence prognosis of lower grade gliomas, including age, histological diagnosis, 1p/19q chromosome arm deletion (codel 1p/19q), isocitrate dehydrogenase (IDH1/IDH2) mutations. Diffusion and Perfusion Weighted Imaging (DWI and PWI) have been proposed as candidates for survival predictors in glioma patients. Methods: To assess the association between mean rCBV, rADC and Cho/Cr ratio values and prognostic biomarkers, we investigated 51 supratentorial grade II (36) and III (15) gliomas by advanced MRI (aMRI), including PWI and DWI, before surgery. Surgical sample histological subtypes and molecular variants (loss of heterozigosity on 1p, 19q, 17p, 9p, 10q; IDH1/IDH2 mutations, O6 methylguanine DNA methyltransferase methylation) were evaluated. Results: rCBV and rADC had significantly different values in gliomas with and without 1p/19q gliomas (2.87±2,4 vs. 1.29±0.93, p = 0.01; 1.55±0,26 vs. 1.81±0.6, p = 0.02 respectively), but not in wild-type and mutated IDH1/IDH2 or grade II and III gliomas (p > 0.05). Cho/Cr ratios were similar in all subgroups. All 1p/19q codeleted patients had mutated IDH1/IDH2. Univariate analysis showed significantly longer PFS in patients with 1p/19q codeletion (84 versus 51 months, p = 0.013), and shorter PFS and OS in wild type IDH1/IDH2 patients (10 versus 60 months, p = 0.0001; 33 versus 80 months, p = 0.0001), after a median follow-up of 60 months. The ROC analysis showed that cut-off values of 1.33 for maximum rCBV and 1.77 for minimum rADC could predict the 1p/19q status with 63.4% sensitivity and 90% specificity (area under the curve 0.72, 95%CI 0.58-0.84) and 65.9% and 80% (area under the curve 0.78, 95%CI 0.62-0.87), respectively. Conclusions: Maximum rCBV and minimum rADC thresholds could help to predict 1p/19q codeletion and to identify lower grade gliomas with a favorable prognosis.
Abstract P039: Encapsulation of Human Mesenchymal Stem Cells in Alginate Microspheres to Enhance Paracrine-Mediated Vascular Recovery
Authors: Natalia Landázuri, Rebecca D Levit, Susan A Safley, Collin J Weber, Athanassios Sambanis, W Robert Taylor
Journal: Circulation Research (2011)

Bone marrow cells migrate to ischemic areas and facilitate revascularization mostly through paracrine mechanisms. As a result, therapeutic strategies for vascular repair have focused on increasing the concentration of these cells at the site of ischemia by direct injection. These strategies have led to encouraging results in clinical trials, yet the number of cells that remain at the site of delivery is very low. The goal of this study is to design an effective cell delivery system to enhance revascularization by maintaining large numbers of cells at the ischemic site, thus increasing the local delivery of angiogenic factors. To achieve this goal, we encapsulated bone marrow derived human mesenchymal stem cells (hMSCs) in non-degradable, barium-gelled alginate spheres prior to delivery to the ischemic site. Our microspheres are biocompatible, do not generate a fibrotic response, and are stable for extended periods of time. They prevent incorporation of cells into the neighboring tissue and protect implanted cells from immune mediated clearance or wash out by the host capillary and lymphatic systems. The microspheres allow diffusion of molecules as large as 80 kDa (which includes most angiogenic factors) but not of larger molecules such as IgG. To test this cell delivery system in vivo, we used a model of murine hind limb ischemia in athymic nude mice. We delivered encapsulated hMSCs, or, as a control, empty capsules, to the ischemic muscle. At various time points, we retrieved the capsules by gentle scooping, then assessed the viability of the encapsulated cells and their protein secretion profile. Approximately 70% of the cells remained viable within the first week and 10-20% within the first month after implantation. In addition, encapsulated cells secreted angiogenic factors (VEGF, bFGF, HGF, angiogenin) in vitro and in vivo. We also assessed recovery of perfusion in the hind limb and found that delivery of encapsulated cells enhanced vascular recovery as compared to empty capsules. The results obtained from this study show that microcapsules are an effective delivery vehicle of therapeutic cells for vascular repair. Encapsulation represents a powerful and highly translatable tool to enhance cell-based therapies in cardiovascular disease.
Molecular Screening for Cancer Treatment Optimization (MOSCATO-01) in Pediatric Patients: A Single-Institutional Prospective Molecular Stratification Trial
Authors: Anne C. Harttrampf, Ludovic Lacroix, Marc Deloger, Frederic Deschamps, Stephanie Puget, Nathalie Auger, Philippe Vielh, Pascale Varlet, Zsofia Balogh, Samuel Abbou, Adrien Allorant, Dominique Valteau-Couanet, Sabine Sarnacki, Louise Gamiche-Rolland, Guillaume Meurice, Veronique Minard-Colin, Jacques Grill, Laurence Brugieres, Christelle Dufour, Nathalie Gaspar, Stefan Michiels, Gilles Vassal, Jean-Charles Soria, Birgit Geoerger
Journal: Clinical Cancer Research (2017)

Abstract Purpose: This single-institutional feasibility study prospectively characterized genomic alterations in recurrent or refractory solid tumors of pediatric patients to select a targeted therapy. Experimental Design: Following treatment failure, patients with signed consent and ages above 6 months, underwent tumor biopsy or surgical resection of primary or metastatic tumor site. These newly acquired samples were analyzed by comparative genomic hybridization array, next-generation sequencing for 75 target genes, whole-exome and RNA sequencing. Biological significance of the alterations and suggestion of most relevant targeted therapies available were discussed in a multidisciplinary tumor board. Results: From December 2012 to January 2016, 75 patients were included, 73 patients underwent 79 interventions, 56 of which were research biopsies with a low complication rate. All patients were pretreated, 37.0% had a brain tumor, and 63.0% had an extra-cranial solid tumor. Median tumor cell content was 70% (range, 0%–100%). Successful molecular analysis in 69 patients detected in 60.9% of patients an actionable alteration in various oncogenic pathways (42.4% with copy-number change, 33.3% with mutation, 2.1% with fusion), and change in diagnosis in three patients. Fourteen patients received 17 targeted therapies; two had received a matched treatment before inclusion. Conclusions: Research biopsies are feasible in advanced pediatric malignancies that exhibit a considerable amount of potentially actionable alterations. Genetic events affecting different cancer hallmarks and limited access to targeted agents within pediatric clinical trials remain the main obstacles that are addressed in our two subsequent precision medicine studies MAPPYACTS and AcSé-ESMART. Clin Cancer Res; 23(20); 6101–12. ©2017 AACR.
Reactivation of hepatitis B virus from an isolated anti-HBc positive patient after eradication of hepatitis C virus with direct-acting antiviral agents
Authors: Tsuyoshi Suda, Tetsuro Shimakami, Takayoshi Shirasaki, Tatsuya Yamashita, Eishiro Mizukoshi, Masao Honda, Shuichi Kaneko
Journal: Journal of Hepatology (2017)
Erratum: Mutations in human TBX5 cause limb and cardiac malformation in Holt-Oram syndrome
Authors: Craig T. Basson, David R. Bachinsky, Robert C. Lin, Tatjana Levi, Jacob A. Elkins, Johann Soults, David Grayzel, Elena Kroumpouzou, Thomas A. Traill, Janine Leblanc-Straceski, Beatrice Renault, Raju Kucherlapati, J.G. Seidman, Christine E. Seidman
Journal: Nature Genetics (1997)
Nonclinical Factors Affecting Shared Decision Making—Reply
Authors: Erica S. Spatz, Benjamin W. Moulton, Harlan M. Krumholz
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Risk Factors and Outcome of Children with Relapsed/Refractory Acute Leukemia after T-Cell-Rich Haploidentical Hematopoietic Cell Transplantation
Authors: Atsushi Kikuta, Hideki Sano, Kazuhiro Mochizuki, Shogo Kobayashi, Mitsuko Akaihata, Yoshihiro Ohara, Yoshinobu Takahashi, Hitoshi Ohto
Journal: Blood (2016)
Abstract 14079: Outside-in Signaling of Integrin α IIb β 3 Mediates Shear-dependent Platelet Microvesicle Formation and Phosphatidylserine Exposure
Authors: Aiming Pang, Yujie Cui, Michael K Delaney, Aleksandra Stojanovic, Xiaoping Du
Journal: Circulation (2016)

Introduction and Hypothesis:  Platelets promote coagulation mainly by exposing membrane phosphatidylserine (PS) and releasing PS-expressing microvesicles (MV). We have recently shown that PS exposure and MV release induced by platelet agonists requires shear stress. To identify the receptor responsible for the shear-dependent signaling leading to PS exposure and MV release, we investigated the hypothesis that Integrin αIIbβ 3  may   play a role in shear-dependent platelet MV release and PS exposure.   Methods and Results:  To determine the role of integrin αIIbβ 3  in shear-dependent PS exposure and MV release, we compared platelets from β 3  -/-  mice and wild-type mice in MV release and PS exposure under shear introduced using a cone-plate rheometer. MV release and PS exposure were determined by flow cytometry. Shear-dependent PS exposure and MV release were significantly suppressed in β 3 -/- platelets. Similarly, Wild type platelets treated with integrin antagonists also showed defective PS exposure and MV release. These data indicate an important role for the ligand binding function of integrin αIIbβ 3  in shear-dependent MV release and PS exposure. To determine whether the role of integrin αIIbβ 3  is due to its outside-in signaling, β 3 -/- platelets were transplanted with wild type β 3  or a mutant β 3  with the critical Gα13 binding site of the β 3  cytoplasmic domain (EEE) changed to alanines (AAA), which selectively abolish outside-in signaling of αIIbβ 3 . Transplantation of wild type β 3  rescued the defective MVs release and PS exposure of β 3 -/- platelets. In contrast, AAA mutant failed to rescue these defects. Consistently, wild type platelets treated with the selective inhibitor of Gα13-integrin interaction, inhibited integrin outside-in signaling and also PS exposure and MV release under shear stress. Furthermore, inhibition of Src, which is important in outside-in signaling downtream of Gα13, also abolished shear-dependent MV release and PS exposure.   Conclusions:  These data suggest that integrin outside-in signaling mediated by the Gα13-β3 interaction and Src-dependent signaling pathway plays an important role in transmitting shear-induced mechanical signals leading to MV release and PS exposure in activated platelets.
European consensus on cancer screening should be applied urgently by health ministers
Authors: M. Arbyn
Journal: BMJ (2001)

EDITOR-The term "absolute coronary risk" is often used without an explicit definition, resulting in confusing inconsistencies.The 1997 Standing Medical Advisory Committee on statin use and the 1998 Joint British recommendations on coronary heart disease prevention say that among people without established coronary heart disease, those with an absolute risk of nonfatal myocardial infarction or
Case 23-2017
Authors: Jason M. Shapiro, Rene Balza, Navneet K. Virk Hundal, Paul E. Hesterberg, Lawrence R. Zukerberg
Journal: New England Journal of Medicine (2017)

A 9-day-old girl was admitted to this hospital because of vomiting, decreased oral intake, and decreased activity. On examination, she appeared to be dehydrated; laboratory evaluation revealed metabolic acidosis and azotemia. A diagnosis was made.
Short vs. continuous gemcitabine infusion in the in vitro cell culture bioreactor system
Authors: Mark Kirstein, Katie Wieman, Brent Williams, James Fisher, Paul Marker, Douglas Yee, Robert Kratzke
Journal: Cancer Research (2007)

1558   Drug exposure impacts the antitumor activity for many chemotherapy agents. Maximum drug concentrations (C max ), Area Under the Curve (AUC), and steady state concentrations (C ss ) may influence antitumor activity. Fixed dose rate (continuous) gemcitabine infusion is superior to short infusion for patients with pancreatic adenocarcinoma, but has not been demonstrated for non-small cell lung cancer (NSCLC). We have developed an  in vitro  bioreactor tissue culture system that allows for changing drug exposure to mimic measured changes in  in vivo  drug concentrations. H2009 cells were grown in the extracapillary space (E.C.S.), and gemcitabine was infused as 3 mg with a syringe pump over either 0.5 (n=5) or 2.5 hr (n=5), followed by mono-exponential elimination to simulate clinically relevant plasma concentrations. Gemcitabine concentrations were measured and cell death was assessed by flow cytometry and colony forming assay (CFA) five days after treatment. For the 0.5 hr infusion, the C max  was (Mean ± SD) 50.8 ± 10.9 μM, clearance was 4.53 ± 0.14 mL/min  and the AUC was 33.2 ± 6.21 μM*hr. For continuous infusions (n=5), the C max  was 15.4 ± 3.91 μM, C ss  was 13.0 ± 0.25, clearance was 4.49 ± 0.08 mL/min, and the AUC, 38.5 ± 9.75 μM*hr. SubG1 were as follows: 42.3 ± 12% 0.5 hr control, 69.6 ± 10% 0.5 hr gemcitabine, 57.2 ± 19.6% 2.5hr control, and 78.2 ± 19.6% 2.5 hr gemcitabine. TUNEL data were as follows: 16.6 ± 7.27% 0.5 hr control, 41.4 ± 16.8% 0.5 hr gemcitabine, 24.8 ± 12.8% 2.5 hr control, and 42.6 ± 19.6% 2.5 hr gemcitabine. CFA survival as follows: 7.08 ± 3.46% 0.5 hr control, 2.12 ± 1.30% 0.5 hr gemcitabine, 4.73 ± 2% 2.5 hr control, and 0.09 ± 0.03% 2.5 hr gemcitabine. Normalized to controls, survival was 15-fold lower for the continuous relative to the short infusion. Studies are on-going to evaluate cellular gemcitabine tri-phosphorylated metabolite amounts, to evaluate cell density on the hollow fibers by microscopy, and to minimize non-drug related cell death. This system can be used to determine the effects of C max  and Css on the induction of cell death, and enables us to characterize optimal exposure-response relationships for investigational agents. Supported by Cancer and Leukemia Group B Junior Faculty Research Award.
Ubiquitin C-Terminal Hydrolase L1 is required for regulated protein degradation through the ubiquitin proteasome system in kidney
Authors: Victoria Radón, Maire Czesla, Julia Reichelt, Julia Fehlert, Anna Hammel, Alva Rosendahl, Jan-Hendrik Knop, Thorsten Wiech, Ulrich O. Wenzel, Marlies Sachs, Anna T. Reinicke, Rolf A.K. Stahl, Catherine Meyer-Schwesinger
Journal: Kidney International (2017)
Efficacy and safety of midostaurin in patients with advanced systemic mastocytosis: 10-year median follow-up of a phase II trial
Authors: D J DeAngelo, T I George, A Linder, C Langford, C Perkins, J Ma, P Westervelt, J D Merker, C Berube, S Coutre, M Liedtke, B Medeiros, D Sternberg, C Dutreix, P-A Ruffie, C Corless, T J Graubert, J Gotlib
Journal: Leukemia (2017)
A patient with a painful and swollen hand
Authors: Alexander EJ Trevatt, William Maynard, Roger Adlard
Journal: BMJ (2017)

A 26 year old man presented to the emergency department with a painful and swollen right hand. The previous night he had punched a wall. He was previously fit and well with no substantial medical history.

On examination his hand was swollen and bruised, but there was no open wound. He had tenderness over the dorsum of the hand, particularly over the fifth metacarpal. There was no obvious deformity, scissoring, or malrotation of the fingers, but he was unable to make a full fist due to the pain. On extension there was an extensor lag of the little finger.

Radiographs were taken (fig 1⇓) and his hand was put in a volar backslab.



Fig 1  Radiographs of the patient’s right hand: anterior-posterior (left), oblique (middle), and lateral (right)





### 1. What injury has the patient sustained?

#### Short answer

The patient has sustained a closed fracture to the neck of the fifth metacarpal of his right hand, also known colloquially as a “boxer’s fracture.” The radiographs show a simple extra-articular fracture with approximately 50° of volar angulation.

#### Discussion

Fractures of the fifth metacarpal are common injuries, accounting for 10% of all hand fractures.1 The five metacarpals make up the body of each hand, articulating proximally with the trapezium, trapezoid, capitates, and hamate, respectively, and distally with the proximal phalanges. The fifth metacarpal articulates proximally with the hamate, laterally with the fourth metacarpal, and distally with the fifth proximal phalanx.

Fractures of the fifth metacarpal most commonly …
Combination of CDK4/6 inhibitor, LY2835219, and mTOR inhibitor to synergistically suppress the growth of head and neck squamous cell carcinoma.
Authors: Myung-Ju Ahn, Bo Mi Ku, Seong Yoon Yi, Jiae Koh, Yeon-Hee Bae, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park
Journal: Journal of Clinical Oncology (2016)

e14118 Background: Despite recent improved understanding of cancer, the 5-year survival rate for head and neck squamous cell carcinoma (HNSCC) remains relatively unchanged. It is critical to identify new therapeutic strategies for NHSCC. Deregulation of CDKN2A (p16) or CCND1 (cyclin D1) occurs commonly in HNSCC and induces sustained cyclin-dependent kinase (CDK) 4/6 activation. In addition, HNSCC is characterized by persistent activation of the AKT/mTOR pathway that triggers a signaling cascade of cell proliferation and survival. Methods: HNSCC cell lines were tested for the CDK4/6 inhibitor LY2835219, alone and in combination with mTOR inhibitor, both in vitro and in vivo. Results: The selective CDK4/6 inhibitor, LY2835219 inhibited CDK4/6-dependent Ser780 phosphorylation in retinoblastoma (RB) and induced cell cycle arrest and growth inhibition. In an animal xenograft model of HNSCC, LY2835219 treatment led to reduced tumor growth. However, because single-agent treatment with LY2835219 showed a limited effect in HNSCC, a combinational strategy is necessary for effective therapy. At the molecular level, we found that LY2835219 inhibited activation of AKT and ERK, but not mTOR. The combination of LY2835219 with mTOR inhibitor was found to be more effective than either drug alone in vitro and in vivo. Conclusions: Taken together, our findings suggest that a combinational treatment with LY2835219 and mTOR inhibitor is a promising therapeutic approach for HNSCC.
Overcoming Imatinib resistance using CAI, a calcium-mediated signal transduction inhibitor: A new therapeutic strategy for chronic myelogenous leucemia
Authors: Chiara Corrado, Simona Fontana, Margherita Giordano, Paolo Colomba, Stefania Raimondo, Ralph Arlinghaus, Elise Kohn, Giacomo De Leo, Riccardo Alessandro
Journal: Cancer Research (2008)

2821  Chronic myelogenous leukemia (CML) is a myeloproliferative disorder characterized by the (9;22) reciprocal chromosomal translocation that produces the so-called Philadelphia (Ph) chromosome. This rearrangement results in the production of the chimeric bcr-abl oncoprotein, p210, with a constitutive tyrosine kinase activity. Although imatinib mesylate (IM) has revolutionized the treatment of CML, some patients develop resistance with progression of leukemia. There is an urgent need for new anticancer agents and combinations that could improve responses and survival rates for CML.  Carboxyamidotriazole (CAI), an inhibitor of calcium-mediated signal transduction, is one of the first cytostatic signal inhibitory anti-cancer drugs; it has been tested in solid tumor patients in Phase I and II clinical trials at the NCI/NIH. Exposure to CAI concentrations of 1-10 µM has anti-tumor activity, inhibiting tumor cell calcium-mediated signal transduction, proliferation and invasion in vitro and tumor metastasis in vivo.  Our preclinical work was aimed to test the possible use of CAI to treat IM-resistant CML. Our results, carried out on three IM-resistant cell lines (LAMA84R, K562R and KCL22R), show that CAI induces a 50% dose-dependent reduction of proliferation rate and a negative modulation of phosphotyrosine protein pattern. All three CML-resistant cell lines displayed a reduction in levels of phosphorylated bcr-abl after CAI exposure. Moreover, CAI is able to inhibit both Bcr/Abl-dependent (e.g. Stat5 and CrkL) and independent signaling pathways (e.g. MAPKs pathway) and to increase (up to 3 fold) the cell death.  On the basis of these results, we started to dissect the molecular mechanisms of action of CAI on IM-resistant CML cells. Therefore, we studied the effects of CAI on three myeloid murine cell lines (32D) transfected with plasmids encoding for BCR/ABL-p210 (full length), BCR/ABL-T315I and BCR/ABL-E255K mutants. T315I and E255K are two BCR/ABL mutations often associated with IM-resistance; the T315I mutation, located in the ATP-binding pocket, makes Imatinib unable to bind the kinase; the E255K mutation, located in the P-loop, maintains the kinase in an inactive conformation. Our results show that CAI is able to reduce the proliferation rate in a dose and time-dependent manner: 61% inhibition for T315I mutant (p value
A multidirectional gravity-assist algorithm that enhances locomotor control in patients with stroke or spinal cord injury
Authors: Jean-Baptiste Mignardot, Camille G. Le Goff, Rubia van den Brand, Marco Capogrosso, Nicolas Fumeaux, Heike Vallery, Selin Anil, Jessica Lanini, Isabelle Fodor, Grégoire Eberle, Auke Ijspeert, Brigitte Schurch, Armin Curt, Stefano Carda, Jocelyne Bloch, Joachim von Zitzewitz, Grégoire Courtine
Journal: Science Translational Medicine (2017)

A robotic harness optimizing gravity-dependent gait interactions enables natural locomotion across activities of daily living in people with spinal cord injury or stroke.