tbuckley/cabot-search huggingface dataset:
Brain invasion in meningiomas—clinical considerations and impact of neuropathological evaluation: a systematic review
Authors: Benjamin Brokinkel, Katharina Hess, Christian Mawrin
Journal: Neuro-Oncology (2017)

With the release of the 2016 edition of the World Health Organization (WHO) Classification of Central Nervous System Tumors, brain invasion in meningiomas has been added as a stand-alone criterion for atypia and can therefore impact grading and indirectly adjuvant therapy. Regarding this rising clinical importance, we have reviewed the current knowledge about brain invasion with emphasis on its implications on current and future clinical practice. We found various definitions of brain invasion and approaches for evaluation in surgically obtained specimens described over the past decades. This heterogeneity is reflected by weak correlation with prognosis and remains controversial. Similarly, associated clinical factors are largely unknown. Preoperative, imaging-guided detection of brain invasion is unspecific, and intraoperative assessment using standard and new high-magnification microscopic techniques remains imprecise. Despite the increasing knowledge about molecular alterations of the tumor/ brain surface, pharmacotherapeutic options targeting brain invasive meningiomas are lacking. Finally, we summarize the impact of brain invasion on histopathological grading in the WHO classifications of brain tumors since 1979.In conclusion, standardized neurosurgical sampling and neuropathological analyses could improve diagnostic reliability and reproducibility of future studies. Further research is needed to improve pre- and intraoperative visualization of brain invasion and to develop adjuvant, targeted therapies.
The why, what, and how of the new FACT standards for immune effector cells
Authors: Marcela V. Maus, Sarah Nikiforow
Journal: Journal for ImmunoTherapy of Cancer (2017)

Novel cellular therapies outside of traditional hematopoietic stem cell transplantation or hematopoietic progenitor cell (HPC) therapy are currently under evaluation in clinical trials across the United States and around the world. Several cellular products, e.g., CD19-directed Chimeric Antigen Receptor (CAR) T cells, are poised for FDA approval and thus increased use at a wider range of academic centers within the next year, with the likelihood of dissemination to standard oncology practice once safety is confirmed. However, these therapies entail some unique challenges in terms of logistics of delivery and toxicity management. Building on experiences and Standards established for HPC programs, the Foundation for the Accreditation of Cellular Therapy (FACT) has established new Standards specific to the use of Immune Effector Cells (IEC), including gene-modified T cells and natural (NK) cells. These Standards specify the clinical and quality infrastructure to facilitate safe administration of immune effector cells and formalize subsequent monitoring and reporting of patient outcomes to enable continual process improvement. Below we detail why these standards came into being, what they entail, and how a clinical team might access educational materials and implement these Standards. We propose that these Standards will be increasingly useful and relied up on as institutions and clinical service lines seek access to these treatment for their patients. FACT will begin accrediting programs that meet these new Standards for clinical administration of Immune Effector Cells in 2017.
Genetic Analysis of Distinct Phenotypic Subsets within MM1.S Multiple Myeloma Cell Line Reveals the Pre-Existence of MM.1R-like Glucocorticoid Resistance and a Sub-Clone with an Activating PI3-Kinase Delta Mutation That Is Preferentially Sensitive to the Selective PI3-Kinase Inhibitor, Idelalisib
Authors: James W Murray, Christopher Fegan, Chris Pepper
Journal: Blood (2016)
TCTAP A-016 Influence of Complete Atrioventricular Block on In-hospital and 12-month Cardiac Mortality in Patients with ST Elevation Myocardial Infarction
Authors: Deuk-Young Nah, Byong-kyu Kim, Jun-Ho Bae, Jin Wook Chung, Moo-Yong Rhee, Kwan Lee, Myung-Ho Jeong, Young Jo Kim
Journal: Journal of the American College of Cardiology (2017)
Nonexceptionalism, Research Risks, and Social Media: Response to Open Peer Commentaries on “Using Social Media as a Research Recruitment Tool: Ethical Issues and Recommendations”
Authors: Luke Gelinas, Robin Pierce, Sabune Winkler, Glenn Cohen, Holly Fernandez Lynch, Barbara E. Bierer
Journal: The American Journal of Bioethics (2017)

We are grateful for the thoughtful commentaries on our target article “Using Social Media as a Research Recruitment Tool: Ethical Issues and Recommendations” (Gelinas et al. 2017), commentaries tha...
Activity of trabectedin and the PARP inhibitor rucaparib in soft-tissue sarcomas
Authors: Audrey Laroche, Vanessa Chaire, François Le Loarer, Marie-Paule Algéo, Christophe Rey, Kevin Tran, Carlo Lucchesi, Antoine Italiano
Journal: Journal of Hematology & Oncology (2017)

Trabectedin has recently been approved in the USA and in Europe for advanced soft-tissue sarcoma patients who have been treated with anthracycline-based chemotherapy without success. The mechanism of action of trabectedin depends on the status of both the nucleotide excision repair (NER) and homologous recombination (HR) DNA repair pathways. Trabectedin results in DNA double-strand breaks. We hypothesized that PARP-1 inhibition is able to perpetuate trabectedin-induced DNA damage.We explored the effects of combining a PARP inhibitor (rucaparib) and trabectedin in a large panel of soft-tissue sarcoma (STS) cell lines and in a mouse model of dedifferentiated liposarcoma.The combination of rucaparib and trabectedin in vitro was synergistic, inhibited cell proliferation, induced apoptosis, and accumulated in the G2/M phase of the cell cycle with higher efficacy than either single agent alone. The combination also resulted in enhanced γH2AX intranuclear accumulation as a result of DNA damage induction. In vivo, the combination of trabectedin and rucaparib significantly enhanced progression-free survival with an increased percentage of tumor necrosis.The combination of PARP inhibitor and trabectedin is beneficial in pre-clinical models of soft-tissue sarcoma and deserves further exploration in the clinical setting.
Dynamo: A Phase 2 Study Demonstrating the Clinical Activity of Duvelisib in Patients with Relapsed Refractory Indolent Non-Hodgkin Lymphoma
Authors: Ian W. Flinn, Carole B. Miller, Kirit M Ardeshna, Scott Tetreault, Sarit E. Assouline, Pier Luigi Zinzani, Jiri Mayer, Michele Merli, Scott D Lunin, Andrew R. Pettitt, Zsolt Nagy, Oliver Tournilhac, Karim Etienne Abou-Nassar, Michael Crump, Eric D. Jacobsen, Sven de Vos, Pedro Santabarbara, Weiliang Shi, Lori Steelman, Nina D. Wagner-Johnston
Journal: Blood (2016)
Case 12-2017 — A 34-Year-Old Man with Nephropathy
Authors: Meghan E. Sise, Grace C. Lo, Robert H. Goldstein, Andrew S. Allegretti, Ricard Masia
Journal: New England Journal of Medicine (2017)

A 34-year-old man presented with worsening renal function. Eleven weeks earlier, fever, fatigue, and decreased appetite had developed. A urinalysis showed proteinuria, and imaging studies revealed nephromegaly. An additional diagnostic procedure was performed.
Coexistence of Two Forms of LTP in ACC Provides a Synaptic Mechanism for the Interactions between Anxiety and Chronic Pain
Authors: Kohei Koga, Giannina Descalzi, Tao Chen, Hyoung-Gon Ko, Jinshan Lu, Shermaine Li, Junehee Son, TaeHyun Kim, Chuljung Kwak, Richard L. Huganir, Ming-gao Zhao, Bong-Kiun Kaang, Graham L. Collingridge, Min Zhuo
Journal: Neuron (2015)
Methotraxate‐Loaded Hybrid Nanoconstructs Target Vascular Lesions and Inhibit Atherosclerosis Progression in ApoE<sup>−/−</sup> Mice
Authors: Cinzia Stigliano, Maricela R. Ramirez, Jaykrishna V. Singh, Santosh Aryal, Jaehong Key, Elvin Blanco, Paolo Decuzzi
Journal: Advanced Healthcare Materials (2017)

Atherosclerosis is an inflammatory disorder characterized by the progressive thickening of blood vessel walls eventually resulting in acute vascular syndromes. Here, intravenously injectable hybrid nanoconstructs are synthesized for tempering immune cell inflammation locally and systemically. Lipid and polymer chains are nanoprecipitated to form 100 nm spherical polymeric nanoconstructs (SPNs), loaded with methotrexate (MTX) and subsequently labeled with Cu 64 and fluorescent probes for combined nuclear/optical imaging. Upon engulfment into macrophages, MTX SPNs intracellularly release their anti‐inflammatory cargo significantly lowering the production of proinflammatory cytokine (interleukin 6 and tumor necrosis factor α) already at 0.06 mg mL −1 of MTX. In ApoE −/− mice, fed with high‐fat diet up to 17 weeks, nuclear and optical imaging demonstrates specific accumulation of SPNs within lipid‐rich plaques along the arterial tree. Histological analyses confirm SPN uptake into macrophages residing within atherosclerotic plaques. A 4‐week treatment with biweekly administration of MTX SPNs is sufficient to reduce the plaque burden in ApoE −/− mice by 50%, kept on high‐fat diet for 10 weeks. Systemic delivery of MTX to macrophages via multifunctional, hybrid nanoconstructs constitutes an effective strategy to inhibit atherosclerosis progression and induce, potentially, the resorption of vascular lesions.
Treatment of Patients With Atrial Fibrillation and Heart Failure With Reduced Ejection Fraction
Authors: Atul Verma, Jonathan M. Kalman, David J. Callans
Journal: Circulation (2017)

Atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF) frequently coexist, and each complicates the course and treatment of the other. Recent population-based studies have demonstrated that the 2 conditions together increase the risk of stroke, heart failure hospitalization, and all-cause mortality, especially soon after the clinical onset of AF. Guideline-directed pharmacological therapy for HFrEF is important; however, although there are various treatment modalities for AF, there is no clear consensus on how best to treat AF with concomitant HFrEF. This in-depth review discusses the available data for the treatment of AF in the setting of HFrEF, focuses on areas where more investigation is necessary, examines the clinical implications of randomized and observational clinical trials, and presents suggestions for individualized treatment strategies for specific patient groups.
Suppressed hepatic bile acid signalling despite elevated production of primary and secondary bile acids in NAFLD
Authors: Na Jiao, Susan S Baker, Adrian Chapa-Rodriguez, Wensheng Liu, Colleen A Nugent, Maria Tsompana, Lucy Mastrandrea, Michael J Buck, Robert D Baker, Robert J Genco, Ruixin Zhu, Lixin Zhu
Journal: Gut (2017)

Objective Bile acids are regulators of lipid and glucose metabolism, and modulate inflammation in the liver and other tissues. Primary bile acids such as cholic acid and chenodeoxycholic acid (CDCA) are produced in the liver, and converted into secondary bile acids such as deoxycholic acid (DCA) and lithocholic acid by gut microbiota. Here we investigated the possible roles of bile acids in non-alcoholic fatty liver disease (NAFLD) pathogenesis and the impact of the gut microbiome on bile acid signalling in NAFLD. Design Serum bile acid levels and fibroblast growth factor 19 (FGF19), liver gene expression profiles and gut microbiome compositions were determined in patients with NAFLD, high-fat diet-fed rats and their controls. Results Serum concentrations of primary and secondary bile acids were increased in patients with NAFLD. In per cent, the farnesoid X receptor (FXR) antagonistic DCA was increased, while the agonistic CDCA was decreased in NAFLD. Increased mRNA expression for cytochrome P450 7A1, Na + -taurocholate cotransporting polypeptide and paraoxonase 1, no change in mRNA expression for small heterodimer partner and bile salt export pump, and reduced serum FGF19 were evidence of impaired FXR and fibroblast growth factor receptor 4 (FGFR4)-mediated signalling in NAFLD. Taurine and glycine metabolising bacteria were increased in the gut of patients with NAFLD, reflecting increased secondary bile acid production. Similar changes in liver gene expression and the gut microbiome were observed in high-fat diet-fed rats. Conclusions The serum bile acid profile, the hepatic gene expression pattern and the gut microbiome composition consistently support an elevated bile acid production in NAFLD. The increased proportion of FXR antagonistic bile acid explains, at least in part, the suppression of hepatic FXR-mediated and FGFR4-mediated signalling. Our study suggests that future NAFLD intervention may target the components of FXR signalling, including the bile acid converting gut microbiome.
Transient tissue priming via ROCK inhibition uncouples pancreatic cancer progression, sensitivity to chemotherapy, and metastasis
Authors: Claire Vennin, Venessa T. Chin, Sean C. Warren, Morghan C. Lucas, David Herrmann, Astrid Magenau, Pauline Melenec, Stacey N. Walters, Gonzalo del Monte-Nieto, James R. W. Conway, Max Nobis, Amr H. Allam, Rachael A. McCloy, Nicola Currey, Mark Pinese, Alice Boulghourjian, Anaiis Zaratzian, Arne A. S. Adam, Celine Heu, Adnan M. Nagrial, Angela Chou, Angela Steinmann, Alison Drury, Danielle Froio, Marc Giry-Laterriere, Nathanial L. E. Harris, Tri Phan, Rohit Jain, Wolfgang Weninger, Ewan J. McGhee, Renee Whan, Amber L. Johns, Jaswinder S. Samra, Lorraine Chantrill, Anthony J. Gill, Maija Kohonen-Corish, Richard P. Harvey, Andrew V. Biankin, T. R. Jeffry Evans, Kurt I. Anderson, Shane T. Grey, Christopher J. Ormandy, David Gallego-Ortega, Yingxiao Wang, Michael S. Samuel, Owen J. Sansom, Andrew Burgess, Thomas R. Cox, Jennifer P. Morton, Marina Pajic, Paul Timpson
Journal: Science Translational Medicine (2017)

Fine-tuned manipulation of tumor tension and vasculature enhances response to chemotherapy and impairs metastatic spread in pancreatic cancer.
Erratum: Corrigendum: The transcription factor STAT5 is critical in dendritic cells for the development of TH2 but not TH1 responses
Authors: Bryan D Bell, Masayuki Kitajima, Ryan P Larson, Thomas A Stoklasek, Kristen Dang, Kazuhito Sakamoto, Kay-Uwe Wagner, Boris Reizis, Lothar Hennighausen, Steven F Ziegler
Journal: Nature Immunology (2014)
Extensive Clinical Evaluations of a Highly Attenuated Live Measles Vaccine
Journal: JAMA (1967)

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Emerging and re-emerging infectious disease threats in South Asia: status, vulnerability, preparedness, and outlook
Authors: Ramanan Laxminarayan, Manish Kakkar, Peter Horby, Gathsaurie Neelika Malavige, Buddha Basnyat
Journal: BMJ (2017)

Without investment in surveillance and early detection the region remains vulnerable to infectious disease threats, say  Buddha Basnyat  and colleagues
Evaluation of Central Nervous System Recurrence of Intravascular Large B-Cell Lymphoma Treated with Rituximab-Containing Chemotherapy
Authors: Kazuyuki Shimada, Takuhei Murase, Kosei Matsue, Masataka Okamoto, Naoaki Ichikawa, Norifumi Tsukamoto, Ako Kikuchi, Yoshio Saburi, Yasufumi Masaki, Nozomi Niitsu, Hiroshi Miwa, Hideki Asaoku, Hiroshi Kosugi, Morio Matsumoto, Makoto Kashimura, Takashi Yoshida, Kazuo Tamura, Kazuhito Yamamoto, Motoko Yamaguchi, Shigeo Nakamura, Tomoki Naoe, Tomohiro Kinoshita
Journal: Blood (2008)
Prognostic and predictive value of primary tumour side in patients with RAS wild-type metastatic colorectal cancer treated with chemotherapy and EGFR directed antibodies in six randomized trials
Authors: D. Arnold, B. Lueza, J.-Y. Douillard, M. Peeters, H.-J. Lenz, A. Venook, V. Heinemann, E. Van Cutsem, J.-P. Pignon, J. Tabernero, A. Cervantes, F. Ciardiello
Journal: Annals of Oncology (2017)
Putaminal Hypometabolism Exceeding Caudate Abnormalities on 18F-FDG PET in Huntington Disease
Authors: Tarun Singhal, Chun K. Kim
Journal: Clinical Nuclear Medicine (2017)

An F-FDG PET scan performed on a patient suspected of having early Huntington disease (HD) showed marked hypometabolism in bilateral putamen that was significantly worse than the hypometabolism in caudate. While HD could not be completely excluded, the scan finding was felt to be somewhat atypical for HD because of a lesser degree of caudate involvement. Genetic testing eventually confirmed the diagnosis of HD. This case shows that diagnosis of HD should still be considered even when putaminal hypometabolism exceeds caudate\ changes on F-FDG PET imaging.
Abstract 210: PPARγ Activation Prevents Cardiac Dysfunction in Sepsis via Stimulation of Energy Production
Authors: Konstantinos Drosatos, Raffay S Khan, Chad M Trent, P Christian Schulze, Shunichi Homma, Ira J Goldberg
Journal: Circulation Research (2012)

Septic cardiac dysfunction has been attributed to either inflammation or suppression of fatty acid oxidation (FAO). We hypothesized that energy deprivation accounts for cardiac dysfunction in lipopolysaccharide (LPS)-induced sepsis. LPS compromised cardiac function, increased cardiac inflammatory markers (interleukin (IL)-1α, IL-6 and tumor necrosis factor (TNF)α) mRNA, and reduced FAO, ATP and FAO-related gene expression: Peroxisome proliferator activating receptor (PPAR)α, cluster of differentiation 36, lipoprotein lipase (LpL), fatty acid transport protein, carnitine palmitoyl-transferase (Cpt)1, PPARγ coactivator (PGC-1)α and PGC-1β in C57BL/6 mice. LC-MS/MS analysis of cardiac lipids showed that total ceramide, which might account for defective FAO and ceramide species were not modulated by LPS. Electron microscopy and ATPase6 DNA levels showed that LPS-treated animals had fewer and smaller cardiac mitochondria. PPARα agonist, WY-14643, did not prevent cardiac dysfunction and suppression of FAO-associated gene expression in LPS-treated mice. In contrast, LPS did not affect cardiac function of mice with cardiomyocyte-specific expression of PPARγ (αMHC-PPARg), although cardiac IL-1α, IL-6 and TNFα mRNA levels were increased. Despite a 77% reduction in PPARα, mRNA levels of FAO-associated genes, such as acyl-CoA oxidase, PGC-1α, PPARδ, Cpt1 increased over 10-fold as compared to saline-treated αMHC-PPARg mice. Similarly, cardiac FAO and ATP content was 2.6 and 5-fold greater in LPS-treated αMHC-PPARγ mice compared to LPS-treated C57BL/6 mice. Moreover, treatment of C57BL/6 mice with LPS and the PPARγ agonist, rosiglitazone, prevented cardiac dysfunction, increased FAO and relevant gene expression, while IL-1α, IL-6 and TNFα mRNA levels increased. Rosiglitazone prevented LPS-mediated reduction of PGC-1α and maintained the number and size of mitochondria. Treatment of C57BL/6 mice with a lethal dose of LPS (15 mg/kg) and repeated doses of rosiglitazone (30mg/kg/day for 72 hours) improved survival, mobility and overall appearance of LPS-treated mice. Thus, PPARγ activation stabilized cardiac energy and prevented cardiac dysfunction and mortality in septic animals despite cardiac inflammation and PPARα downregulation.
Moving toward endotypes in atopic dermatitis: Identification of patient clusters based on serum biomarker analysis
Authors: Judith L. Thijs, Ian Strickland, Carla A.F.M. Bruijnzeel-Koomen, Stefan Nierkens, Barbara Giovannone, Eszter Csomor, Bret R. Sellman, Tomas Mustelin, Matthew A. Sleeman, Marjolein S. de Bruin-Weller, Athula Herath, Julia Drylewicz, Richard D. May, DirkJan Hijnen
Journal: Journal of Allergy and Clinical Immunology (2017)
Functional Magnetic Resonance Imaging to Assess the Neurobehavioral Impact of Dysphotopsia with Multifocal Intraocular Lenses
Authors: Andreia M. Rosa, Ângela C. Miranda, Miguel Patrício, Colm McAlinden, Fátima L. Silva, Joaquim N. Murta, Miguel Castelo-Branco
Journal: Ophthalmology (2017)
TCTAP A-054 Drug Eluting Stent Reduces All Causes Mortality in Left Main Stenting When Compared with Bare Metal Stent (Hong Kong Left Main Stenting Registry)
Authors: Jaclyn Chi Lin Chan, Ping Tim Tsui, Dick Chi Yeung Cheung, Alan Chan, Li Wah Tam, Eugene Brian Wu, Michael Kang-Yin Lee, Man-Hong Jim, Tak Sun Tse, Edmond Wong, Yu Ho Chan, Kin Lam Tsui
Journal: Journal of the American College of Cardiology (2017)
SETD2 Functional Loss through Mutation or Genetic Deletion Promotes Expansion of Normal and Malignant γδ T Cells through Loss of Tumor Suppressor Function and Upregulation of Oncogenic Pathways
Authors: Matthew S. McKinney, Andrea B. Moffitt, Rachel E Rempel, Deepthi Rajagopalan, Jane Healy, Tiffany Tzeng, Jyotishka Datta, Cassandra Love, David Dunson, Yuan Zhuang, Sandeep Dave
Journal: Blood (2016)
Abstract 84: Atrial Fibrillation Causes a Progressive, Time-Dependent Reduction in Myocardial Neuronal NOS in Humans and Goats: Implications for AF-Induced Electrical Remodeling
Authors: Svetlana Reilly, Xing Liu, Raja Jayaram, Sunder Verheule, Uli Schotten, Barbara Casadei
Journal: Circulation Research (2012)

Rationale: Nitric oxide (NO) plays a key role in the regulation of cardiac and endothelial function and thrombogenesis. Atrial fibrillation (AF) has been associated with reduced NO availability but the mechanisms and implications of this finding remain to be fully investigated. Methods and Results: We evaluated NO synthase (NOS) activity and localization in right atrial (RA) tissue from 30 patients with permanent AF (vs. 65 controls in sinus rhythm, SR), and in the RA and left atrial (LA) tissue of 48 goats after 2 weeks (2W) and 6 months (6M) of pacing-induced AF. NOS activity was uncoupled in RA tissue from patients and goats in 6M-AF, and was caused by a reduction in BH4 tissue concentration and by an increase in arginase activity (HPLC). Although BH4 and arginine supplementation re-coupled NOS, it did not abolish the difference in NOS activity between AF and SR. Immunoblotting and immunolocalization revealed a progressive reduction in bi-atrial neuronal NOS (nNOS) protein with the duration of AF (by 65% at 2W, 86% at 6M in goats and by 62% in patients with AF) and a reduction in eNOS in long-standing AF. nNOS was reduced in atrial myocytes but not in neuronal tissue. The mRNA expression of NOS (qRT-PCR) was unaltered; however, the reduction in nNOS protein in AF was associated with an increase in nNOS ubiquitination which was partially reversed by inhibition of proteosomal activity with MG132; inhibition of the autophagy-lysosomal pathway with bafilomycin A1 did not restore nNOS protein. To investigate the electrophysiological consequences of a reduced nNOS in LA and RA myocytes, we compared electrical properties of the isolated atrial myocytes from nNOS-/- mice (n=18) and their wild type (WT) littermates after nNOS inhibition with SMTC. Both nNOS gene deletion and inhibition impaired myocytes' relaxation in both RA and LA, and result in a slower rate of decay of [Ca2+]i transient in the LA myocytes only. Conclusions: A reduction in bi-atrial nNOS activity and protein level is an early event in the natural history of AF that results in a chamber-specific effect on electrical properties of the myocytes.