tbuckley/cabot-search huggingface dataset:
Abstract 15637: Elective Admissions for Congestive Heart Failure Are Associated With Higher Inpatient Mortality and Hospital Costs, a Nationwide Analysis Using the National Inpatient Database of 2013
Authors: Alejandro Lemor, Shawn Lee, Farid Gholitabar, Carlos A Gongora, Abel Casso Dominguez, Paul T Kroner, Daniel Castaneda, Carolina Hurtado, Eyal Herzog
Journal: Circulation (2016)

Background: Congestive heart failure (CHF) is one of the most common causes of hospital admissions and readmissions in the United States. The majority of patients with CHF who visit the emergency d...
Phase 0 Trial of AZD1775 in First-Recurrence Glioblastoma Patients
Authors: Nader Sanai, Jing Li, Julie Boerner, Karri Stark, Jianmei Wu, Seongho Kim, Alanna Derogatis, Shwetal Mehta, Harshil D. Dhruv, Lance K. Heilbrun, Michael E. Berens, Patricia M. LoRusso
Journal: Clinical Cancer Research (2018)

Abstract Purpose: AZD1775 is a first-in-class Wee1 inhibitor with dual function as a DNA damage sensitizer and cytotoxic agent. A phase I study of AZD1775 for solid tumors suggested activity against brain tumors, but a preclinical study indicated minimal blood–brain barrier penetration in mice. To resolve this controversy, we examined the pharmacokinetics and pharmacodynamics of AZD1775 in patients with first-recurrence, glioblastoma. Patients and Methods: Twenty adult patients received a single dose of AZD1775 prior to tumor resection and enrolled in either a dose-escalation arm or a time-escalation arm. Sparse pharmacokinetic blood samples were collected, and contrast-enhancing tumor samples were collected intraoperatively. AZD1775 total and unbound concentrations were determined by a validated LC/MS-MS method. Population pharmacokinetic analysis was performed to characterize AZD1775 plasma pharmacokinetic profiles. Pharmacodynamic endpoints were compared to matched archival tissue. Results: The AZD1775 plasma concentration–time profile following a single oral dose in patients with glioblastoma was well-described by a one-compartment model. Glomerular filtration rate was identified as a significant covariate on AZD1775 apparent clearance. AZD1775 showed good brain tumor penetration, with a median unbound tumor-to-plasma concentration ratio of 3.2, and achieved potential pharmacologically active tumor concentrations. Wee1 pathway suppression was inferred by abrogation of G2 arrest, intensified double-strand DNA breakage, and programmed cell death. No drug-related adverse events were associated with this study. Conclusions: In contrast to recent preclinical data, our phase 0 study of AZD 1775 in recurrent glioblastoma indicates good human brain tumor penetration, provides the first evidence of clinical biological activity in human glioblastoma, and confirms the utility of phase 0 trials as part of an accelerated paradigm for drug development in patients with glioma. Clin Cancer Res; 24(16); 3820–8. ©2018 AACR. See related commentary by Vogelbaum, p. 3790
Integrin a5 is an independent prognosis factor and a potential therapeutic target for breast cancer bone metastasis
Authors: F. Pantano, M. Croset, K. Driouch, M. Iuliani, M. Fioramonti, D. Santini, G. Tonini, N. Bednarz-Knoll, K. Pantel, P. Clézardin
Journal: Annals of Oncology (2016)
Aminopeptidase antibodies in mesothelioma: new wine deserves new sacks
Authors: Jan P. van Meerbeeck, Gerrit Jansen, Elisa Giovannetti, Godefridus J. Peters
Journal: European Respiratory Journal (2018)

<b>Aminopeptidase antibodies are a new class of agents in mesothelioma; their development will require strategic clinical trials. Exploring activity and efficacy according to old paradigms may lead to their disruptive characteristics being disregarded.</b>http://ow.ly/3XLU30jUpqf
Who Should Try New Antibody Treatments for Migraine?
Authors: Elizabeth W. Loder, Rebecca C. Burch
Journal: JAMA Neurology (2018)

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
Ampli: A Construction Set for Paperfluidic Systems
Authors: Elizabeth A. Phillips, Anna K. Young, Nikolas Albarran, Jonah Butler, Kaira Lujan, Kimberly Hamad‐Schifferli, Jose Gomez‐Marquez
Journal: Advanced Healthcare Materials (2018)

The design and fabrication of reconfigurable, modular paperfluidics driven by a prefabricated reusable block library, asynchronous modular paperfluidic linear instrument-free (Ampli) block, are reported. The blocks are inspired by the plug-and-play modularity of electronic breadboards that lower prototyping barriers in circuit design. The resulting biochemical breadboard is a paperfluidic construction set that can be functionalized with chemical, biological, and electrical elements. Ampli blocks can form standard paperfluidic devices without any external instrumentation. Furthermore, their modular nature enhances fluidics in ways that fixed devices cannot. The blocks' ability to start, stop, modify, and reverse reaction flows, reagents, and rates in real time is demonstrated. These enhancements allow users to increase colorimetric signals, fine tune reaction times, and counter check multiplexed diagnostics for false positives or negatives. The modular construction demonstrates that field-ready, distributed fabrication of paper analytical systems can be standardized without requiring the "black box" of craft and technique inherent in paper-based systems. Ampli assembly and point-of-care redesign extends the usability of paper analytical systems and invites user-driven prototyping beyond the lab setting demonstrating "Design for Hack" in diagnostics.
Stability of the Brain Functional Connectome Fingerprint in Individuals With Schizophrenia
Authors: Tobias Kaufmann, Dag Alnæs, Christine L. Brandt, Francesco Bettella, Srdjan Djurovic, Ole A. Andreassen, Lars T. Westlye
Journal: JAMA Psychiatry (2018)

This study combines data from 3 existing functional magnetic resonance imaging data sets of people with schizophrenia spectrum disorders and healthy controls to assess the association of schizophrenia spectrum disorders with connectome stability.
Clinical and Pathologic Characteristics of Pulmonary Carcinoid Tumors in Central and Peripheral Locations
Authors: George Papaxoinis, Angela Lamarca, Anne Marie Quinn, Wasat Mansoor, Daisuke Nonaka
Journal: Endocrine Pathology (2018)

Pulmonary carcinoid tumors occur in both central and peripheral locations, and some differences in clinico-pathological features have long been observed. We investigated a large number of resected carcinoid tumors with the aim to further define the characteristics of tumors from both locations. One hundred sixty-six resected carcinoid tumors of the lung were analyzed for a variety of clinical and pathologic features, including histology subtype, mitotic rate, Ki67 index, necrosis, invasive pattern, architectural pattern, cell morphology, sustentacular cells, neuroendocrine hyperplasia, and orthopedia homeobox protein (OTP) and TTF-1 immunohistochemical expressions. Unsupervised hierarchical cluster analysis suggested three clusters as the best solution using TTF-1 and OTP expression: TTF-1-positive and OTP-positive tumors as cluster 1, TTF-1-positive but OTP-negative as cluster 2, and TTF-1-negative and OTP-negative as cluster 3. Cluster 1 was characterized by peripheral location, presence of spindle cell component, presence of sustentacular cells, female predominance, and strong association with neuroendocrine hyperplasia. Cluster 2 was characterized by central location, polygonal cell morphology, acinar growth pattern in a subset of tumors, and only rare association with neuroendocrine hyperplasia. Cluster 3 consisted of more aggressive tumors with more heterogeneous pathologic features. Tumors showed polygonal cell morphology and acinar growth pattern. Occurrence of neuroendocrine hyperplasia was exceptional. Our study confirmed distinct characteristics of central and peripheral type carcinoid. An important difference was a strong association of the peripheral tumor with neuroendocrine hyperplasia while such an association in central tumors was negligible. The tumor location might be relevant for pathobiology of lung carcinoid tumors.
Abstract A18: Generation of new conditional Kras-alleles by CRISPR-based genome editing
Authors: Maria Paz Zafra, Emma M. Schatoff, Teng Han, Lukas E. Dow
Journal: Cancer Research (2018)

Abstract KRAS is the most frequently mutated oncogene in human cancers, and specific cancer types show a clear bias in the types and frequency of Kras alterations. However, we do not have a clear understanding of how distinct Kras mutations dictate tumor biology and response to therapy. The generation of conditional animal models, such as Lox-Stop-Lox (LSL) KrasG12D and LSL-KrasG12Vgeo mice, has provided important tools to dissect the impact of Kras mutation in tumor development, but these models alone do not recapitulate the spectrum of Kras alterations in human cancer. To better reflect the Kras mutational landscape in human cancers, we have developed a series of critical LSL-Kras mouse models that recapitulate common Kras alterations observed in colorectal (G13D), pancreatic (G12R), and lung cancer (G12C), allowing the direct interrogation of the effects of these Kras mutations on disease phenotype and treatment response. To do this, we targeted embryonic stem cells (ESCs) carrying the LSL-KrasG12D allele, by co-transfection of a modified high-fidelity Cas9 (Cas9-HFz), a LSL-Kras-targeted sgRNA, and an HDR template carrying the new mutation. While Cas9-HFz displayed a slight decrease in homology-directed repair (HDR) efficiency in comparison with wild-type Cas9, it enabled high specificity editing of only the LSL allele. Targeted deep sequencing revealed a significant reduction in “off-target” events in wild-type Kras locus in Cas9-HFz transfected samples compared to unmodified Cas9. We next generated transgenic mice by blastocyst injection and produced mice carrying each LSL-Kras variant, a pancreas-specific Cre (p48-Cre), and a far-red fluorescent Cre-reporter (mKate2). We are now analyzing the impact of specific Kras alterations in tumor initiation in distinct tissues such as the pancreas, colon, and lung. Together with available LSL-KrasG12D and LSL-KrasG12V already available, our new alleles will serve as critical tools for better dissecting the genetic factors that dictate disease initiation, progression, and response to therapy. Citation Format: Maria Paz Zafra, Emma M. Schatoff, Teng Han, Lukas E. Dow. Generation of new conditional Kras-alleles by CRISPR-based genome editing [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr A18.
Epidemiology of respiratory pathogen carriage in the homeless population within two shelters in Marseille, France, 2015–2017: cross sectional 1-day surveys
Authors: T.D.A. Ly, S. Edouard, S. Badiaga, H. Tissot-Dupont, V.T. Hoang, V. Pommier de Santi, P. Brouqui, D. Raoult, P. Gautret
Journal: Clinical Microbiology and Infection (2018)
Time to adjuvant chemotherapy in CEA-positive colon cancer: An NCDB analysis.
Authors: Yang Zhang, Sarah J Aurit, Mohan Satish, Eugene Chau, Peter T. Silberstein
Journal: Journal of Clinical Oncology (2018)

603 Background: It is well accepted that positive serum carcinoembryonic antigen (CEA) levels are associated with inferior survival in patients with advanced non-metastatic colon cancer; however, it is not fully elucidated whether this prognostic factor can inform clinical decisions, specifically for the optimal timing of adjuvant chemotherapy after definitive surgical treatment. This study was aimed to determine the relationship between onset of adjuvant chemotherapy and rate of survival in stage III colon cancer patients who tested CEA-positive, and thus, potentially identifying the optimal timing to increase survivorship. Methods: We identified 19,180 patients from the NCDB with TNM pathologic stage IIIB and IIIC adenocarcinoma of the colon who also had a recorded CEA test result and whom had received adjuvant chemotherapy. We examined unadjusted overall survival based on CEA status with the Kaplan-Meier method. A multivariable Cox regression model was estimated to determine the association of CEA status and overall survival after controlling for site, stage, days from surgery to chemotherapy, demographic background, and facility characteristics. All analyses were conducted with SAS version 9.4 (SAS Institute Inc., Cary, NC) with a statistical threshold of p &lt; 0.05. Results: Based on the log-rank χ 2 test, a positive CEA test result was significantly associated with worse survival. We adjusted for patient and facility level characteristics, and found a 49.7% increased risk of death for a patient with a positive CEA result (95% CI: 41.7% to 58.2%). We found a median number of 43 days from definitive surgery to initiation of chemotherapy; after adjusting for all other variables, we found for every ten-day delay in receiving adjuvant therapy after definitive surgical intervention, there was a 1.6% increased risk of death (95% CI: 1.0 to 2.2%). Conclusions: In this cohort of patients who tested CEA-positive, delays in receiving adjuvant chemotherapy had a negative linear association on survival. Adjuvant therapy should be considered as soon as patient’s clinical condition permits.
The Long Noncoding RNA Cancer Susceptibility 9 and RNA Binding Protein Heterogeneous Nuclear Ribonucleoprotein L Form a Complex and Coregulate Genes Linked to AKT Signaling
Authors: Marcel Klingenberg, Matthias Groß, Ashish Goyal, Maria Polycarpou‐Schwarz, Thilo Miersch, Anne‐Sophie Ernst, Jörg Leupold, Nitin Patil, Uwe Warnken, Heike Allgayer, Thomas Longerich, Peter Schirmacher, Michael Boutros, Sven Diederichs
Journal: Hepatology (2018)

The identification of viability-associated long noncoding RNAs (lncRNAs) might be a promising rationale for new therapeutic approaches in liver cancer. Here, we applied an RNA interference screening approach in hepatocellular carcinoma (HCC) cell lines to find viability-associated lncRNAs. Among the multiple identified lncRNAs with a significant impact on HCC cell viability, we selected cancer susceptibility 9 (CASC9) due to the strength of its phenotype, expression, and up-regulation in HCC versus normal liver. CASC9 regulated viability across multiple HCC cell lines as shown by clustered regularly interspaced short palindromic repeats interference and single small interfering RNA (siRNA)-mediated and siRNA pool-mediated depletion of CASC9. Further, CASC9 depletion caused an increase in apoptosis and a decrease of proliferation. We identified the RNA binding protein heterogeneous nuclear ribonucleoprotein L (HNRNPL) as a CASC9 interacting protein by RNA affinity purification and validated it by native RNA immunoprecipitation. Knockdown of HNRNPL mimicked the loss-of-viability phenotype observed upon CASC9 depletion. Analysis of the proteome (stable isotope labeling with amino acids in cell culture) of CASC9-depleted and HNRNPL-depleted cells revealed a set of coregulated genes which implied a role of the CASC9:HNRNPL complex in AKT signaling and DNA damage sensing. CASC9 expression levels were elevated in patient-derived tumor samples compared to normal control tissue and had a significant association with overall survival of HCC patients. In a xenograft chicken chorioallantoic membrane model, we measured decreased tumor size after knockdown of CASC9. Conclusion: Taken together, we provide a comprehensive list of viability-associated lncRNAs in HCC; we identified the CASC9:HNRNPL complex as a clinically relevant viability-associated lncRNA/protein complex which affects AKT signaling and DNA damage sensing in HCC.
Differentiation of periapical granulomas and cysts by using dental MRI: a pilot study
Authors: Alexander Juerchott, Thorsten Pfefferle, Christa Flechtenmacher, Johannes Mente, Martin Bendszus, Sabine Heiland, Tim Hilgenfeld
Journal: International Journal of Oral Science (2018)

Abstract The purpose of this pilot study was to evaluate whether periapical granulomas can be differentiated from periapical cysts in vivo by using dental magnetic resonance imaging (MRI). Prior to apicoectomy, 11 patients with radiographically confirmed periapical lesions underwent dental MRI, including fat-saturated T2-weighted (T2wFS) images, non-contrast-enhanced T1-weighted images with and without fat saturation (T1w/T1wFS), and contrast-enhanced fat-saturated T1-weighted (T1wFS+C) images. Two independent observers performed structured image analysis of MRI datasets twice. A total of 15 diagnostic MRI criteria were evaluated, and histopathological results (6 granulomas and 5 cysts) were compared with MRI characteristics. Statistical analysis was performed using intraclass correlation coefficient (ICC), Cohen’s kappa (κ), Mann–Whitney U -test and Fisher’s exact test. Lesion identification and consecutive structured image analysis was possible on T2wFS and T1wFS+C MRI images. A high reproducibility was shown for MRI measurements of the maximum lesion diameter (intraobserver ICC = 0.996/0.998; interobserver ICC = 0.997), for the “peripheral rim” thickness (intraobserver ICC = 0.988/0.984; interobserver ICC = 0.970), and for all non-quantitative MRI criteria (intraobserver-κ = 0.990/0.995; interobserver-κ = 0.988). In accordance with histopathological results, six MRI criteria allowed for a clear differentiation between cysts and granulomas: (1) outer margin of lesion, (2) texture of “peripheral rim” in T1wFS+C, (3) texture of “lesion center” in T2wFS, (4) surrounding tissue involvement in T2wFS, (5) surrounding tissue involvement in T1wFS+C and (6) maximum “peripheral rim” thickness (all: P &lt; 0.05). In conclusion, this pilot study indicates that radiation-free dental MRI enables a reliable differentiation between periapical cysts and granulomas in vivo. Thus, MRI may substantially improve treatment strategies and help to avoid unnecessary surgery in apical periodontitis.
HYBRID NOTES – COMPLETE ENDOSCOPIC RESECTION OF THE GASTRIC WALL ASSISTED BY LAPAROSCOPY IN A GASTRIC FUNDUS GIST
Authors: J Fernandes, D Libânio, L Lopes
Journal: Endoscopy (2018)

The authors present the case of a 33-year-old woman with a 15-mm subepithelial lesion located in the gastric fundus.
Diagnostic Performance of Coronary CTA in Intermediate-to-High-Risk Patients for Suspected Acute Coronary Syndrome
Authors: Jan-Erik Scholtz, Daniel Addison, Daniel O. Bittner, Sumbal Janjua, Borek Foldyna, Sandeep Hedgire, Pedro V. Staziaki, James L. Januzzi, John T. Nagurney, Nina Meyersohn, Michael T. Lu, Tomas G. Neilan, Udo Hoffmann, Brian B. Ghoshhajra
Journal: JACC. Cardiovascular imaging (2018)
The NOTCH1/CD44 axis drives pathogenesis in a T cell acute lymphoblastic leukemia model
Authors: Marina García-Peydró, Patricia Fuentes, Marta Mosquera, María J. García-León, Juan Alcain, Antonio Rodríguez, Purificación García de Miguel, Pablo Menéndez, Kees Weijer, Hergen Spits, David T. Scadden, Carlos Cuesta-Mateos, Cecilia Muñoz-Calleja, Francisco Sánchez-Madrid, María L. Toribio
Journal: Journal of Clinical Investigation (2018)

NOTCH1 is a prevalent signaling pathway in T cell acute lymphoblastic leukemia (T-ALL), but crucial NOTCH1 downstream signals and target genes contributing to T-ALL pathogenesis cannot be retrospectively analyzed in patients and thus remain ill defined. This information is clinically relevant, as initiating lesions that lead to cell transformation and leukemia-initiating cell (LIC) activity are promising therapeutic targets against the major hurdle of T-ALL relapse. Here, we describe the generation in vivo of a human T cell leukemia that recapitulates T-ALL in patients, which arises de novo in immunodeficient mice reconstituted with human hematopoietic progenitors ectopically expressing active NOTCH1. This T-ALL model allowed us to identify CD44 as a direct NOTCH1 transcriptional target and to recognize CD44 overexpression as an early hallmark of preleukemic cells that engraft the BM and finally develop a clonal transplantable T-ALL that infiltrates lymphoid organs and brain. Notably, CD44 is shown to support crucial BM niche interactions necessary for LIC activity of human T-ALL xenografts and disease progression, highlighting the importance of the NOTCH1/CD44 axis in T-ALL pathogenesis. The observed therapeutic benefit of anti-CD44 antibody administration in xenotransplanted mice holds great promise for therapeutic purposes against T-ALL relapse.
Abstract 20840: Feasibility of a Visualization Radio Frequency Balloon Catheter for Epicardial Ablation
Authors: Nitish Badhwar, Amin Al-Ahmad, Marian Rippy, Vivek Reddy, Girish Narayan, Karl Heinz Kuck, Ian Crozier, Matt Daly, Iain Melton, Tomos E Walters, Randall J Lee, Byron Lee
Journal: Circulation (2016)

Introduction: Epicardial ablation has been shown to improve VT outcomes, but is generally used after a failed attempt of endocardial ablation. The potential of injuring epicardial coronary arteries...