tbuckley/cabot-search huggingface dataset:
HGG-17. PEDIATRIC RADIATION-INDUCED GLIOBLASTOMA: TRANSCRIPTOMIC AND DRUG SCREENING ANALYSIS OF PRIMARY PATIENT SAMPLES
Authors: John DeSisto, Andrew Donson, Patrick Flannery, Rakeb Lemma, Bridget Sanford, Nicholas Foreman
Journal: Neuro-Oncology (2017)

BACKGROUND: Cranial radiation therapy (RT) for pediatric cancer is a major risk factor for glioblastoma. Pediatric radiation-induced glioblastoma (RIG) is poorly understood, incurable, and unresponsive to treatment. We previously found that RIG’s array gene expression profile differs from spontaneous pediatric glioblastoma, raising hope that RIG may respond to different treatments. METHODS: 11 RIG patients undergoing resection from 1995–2014 were identified; RNA was extracted from each tumor and seven matched blood samples. RNA-Seq was conducted, and mutation and geneset enrichment analysis (GSEA) performed. Two samples were grown as cell lines immediately following surgery and utilized for drug screening and validation using a panel of all FDA-approved chemotherapy agents. RESULTS: RIG samples formed two distinct clustering subgroups on GSEA. One group showed upregulated mesenchymal characteristics, compared to pro-neural and neural characteristics in the other (false discovery rate (FDR)<0.05), resembling molecular subgroups previously identified in adult glioblastoma. The mesenchymal group was more differentiated (FDR<0.05) and showed bystander irradiation effect, including NF-kB pathway upregulation, versus no discernible radiation effect in the neural group (FDR<0.05). The neural group trended toward longer latency than the mesenchymal group from RT to RIG onset (9.8 vs 6.0 years, p=0.07). Germline samples lacked common oncogenic mutations, although one had a heterozygous missense variant (A16C) in TP53BP2, a critical TP53 cofactor. Drug screening and validation identified several agents effective in RIG cell lines from both groups, including vinblastine, etoposide, and paclitaxel (IC50 1–800 nM). The mesenchymal line was also sensitive to proteasome inhibitors, which we attributed through immunofluorescence studies to preservation of cytoplasmic IKB-a versus untreated (p<0.05), resulting in NF-kB inhibition, an effect not seen in the neural line. CONCLUSIONS: RIGs divide into mesenchymal and neural groups on transcriptomic analysis, with the mesenchymal group showing greater radiation effect. Drug screening reveals candidate FDA-approved chemotherapy drugs that should be further investigated.
Until the demise of the functional field of view
Authors: Laurent Itti
Journal: Behavioral and Brain Sciences (2017)

Abstract Hulleman &amp; Olivers (H&amp;O) make a much-needed stride forward for a better understanding of visual search behavior by rejecting theories based on discrete stimulus items. I propose that the framework could be further enhanced by clearly delineating distinct mechanisms for attention guidance, selection, and enhancement during visual search, instead of conflating them into a single functional field of view.
Pilot survey regarding “the green folder” – an educator-designed secondary school return to learn protocol after a sport-related concussion
Authors: James D Carson, Aliya Safwan, Sari A Kraft, Nariko Kuwahara, Stefanie E Moser, Sarah T Rabinovitch, Qurat-ul-Ain Mansoora, Vijitha Jegatheesan, Rahim Moineddin, Pierre Fremont
Journal: British Journal of Sports Medicine (2017)

Objective To demonstrate whether a user-centred (teacher accepted and student focused) return to learn (RTL) protocol after a sport-related concussion (SRC)has an efficacious role. Design Prospective pilot survey. Setting Four sport medicine clinics in Ontario, Canada. Participants Twenty-eight collegiate athletes (21 males and 7 females: age=20.2 ± 1.7 years, height=182.2 ± 11.9 cm, mass=90.3 ± 24.2 kg) without history of: headaches or migraines, substances/alcohol abuse, and/or psychiatric conditions. Intervention NineSRC students from one (index) school who used the new protocol and a control group (11 SRC students) from other schools, who did not use the new protocol,completed a web-based survey. Outcome measures Primary outcome measures include student perception of school support during their SRC RTL. Main results Twenty surveys were completed from an eligible 52 students (38.5%).Among students who received the Green Folder at the index school, 71.4% either strongly or mostly agreed thatsuch an RTL protocol could shorten the duration of SRC symptoms. At that school, 100% strongly or mostly agreed (versus 14.3% from the other schools) that the school was very helpful advising about the RTL steps and when they should return to school. 85.7% of students at the index school versus 28.6% from other schools, strongly or mostly agree that the school staff fully understands RTL strategies after SRC. Conclusions The “Green Folder” incorporating RTL steps and a daily class-by-class accommodation sign off by a guidance counsellor, appears to have perceived efficacy for SRC students. Further research will determine whether such a user-centred RTL protocol results in a more efficacious implementation of expert recommendations about concussion management, worthy of widespread dissemination. Competing interests None.
A benign colorectal lesion with amorphous pit (Kudo Vn) and avascular pattern (Sano’s 3b): differential diagnosis with deep invasive adenocarcinoma
Authors: Sophie Testu, Clémence Morin, Jérôme Rivory, Martin Fabritius, Jean-Christophe Saurin, Thierry Ponchon, Mathieu Pioche
Journal: Endoscopy (2017)

Endoscopic analysis with virtual chromoendoscopy, including narrow-band imaging (NBI), allows the prediction of histology and invasion depth for neoplastic lesions in the colon.
Conventional Radiation Therapy Compared With Stereotactic Conformal Therapy—A Rare and Laudable Randomized Trial
Authors: Nancy P. Mendenhall, Thomas J. Fitzgerald
Journal: JAMA Oncology (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 Oncology 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 Oncology journal
Emerging roles of chromatin in the maintenance of genome organization and function in plants
Authors: Zaida Vergara, Crisanto Gutierrez
Journal: Genome biology (2017)

Chromatin is not a uniform macromolecular entity; it contains different domains characterized by complex signatures of DNA and histone modifications. Such domains are organized both at a linear scale along the genome and spatially within the nucleus. We discuss recent discoveries regarding mechanisms that establish boundaries between chromatin states and nuclear territories. Chromatin organization is crucial for genome replication, transcriptional silencing, and DNA repair and recombination. The replication machinery is relevant for the maintenance of chromatin states, influencing DNA replication origin specification and accessibility. Current studies reinforce the idea of intimate crosstalk between chromatin features and processes involving DNA transactions.
Influence of hydroxypropyl methylcellulose, methylcellulose, gelatin, poloxamer 407 and poloxamer 188 on the formation and stability of soybean oil-in-water emulsions
Authors: Miao Zhang, Baixue Yang, Wei Liu, Sanming Li
Journal: Asian Journal of Pharmaceutical Sciences (2017)

Macromolecules of polysaccharides, proteins and poloxamers have a hydrophobic portion and a hydrophilic one that can be used as emulsifiers. Parts of these emulsifiers are safe pharmaceutical excipients, which can replace the irritant low molecular weight surfactants to formulate emulsions for the pharmaceutical field. This project focused on preparing O/W emulsions stabilized with polymers for pharmaceuticals such as polysaccharides, proteins and poloxamers, including hydroxypropyl methylcellulose (HPMC), methylcellulose (MC), gelatin, poloxamer 407 (F127) and poloxamer 188 (F68). Emulsion physical stability was assessed by centrifugation, autoclaving sterilization and droplet size measurements. The stabilization mechanisms of emulsions were determined by interfacial tension and rheological measurements. Results stated that the efficacy of these polymers for pharmaceuticals stabilized emulsions was sorted in the order: F127 > F68 > HPMC > MC > Gelatin.
EPND-01. THE ACTIVE REGULATORY LANDSCAPE OF EPENDYMAL TUMORS
Authors: Stephen Mack, Kristian Pajtler, Lukas Chavez, Stefan Pfister, Marcel Kool, Michael Taylor, Jeremy Rich
Journal: Neuro-Oncology (2017)

Genomic sequencing has driven precision-based oncology therapy; however, genetic drivers remain unknown or non-targetable for many malignancies, demanding alternative approaches to identify therapeutic leads. Ependymomas comprise histologically similar tumour entities driven by distinct molecular mechanisms, such as fusion oncoproteins, genome-wide chromosomal instability, or disruption of DNA methylation patterns. Despite these differences, ependymomas commonly resist chemotherapy and lack available targeted agents for clinical trial development. In the case of genomically balanced ependymomas, and those driven by fusion oncoproteins, we hypothesized that the chromatin landscapes could uncover oncogenes that would inform actionable targets for therapy and reveal specific transcriptional circuitries to identify the molecular origins of the disease. To this end, we mapped active chromatin landscapes in 42 primary ependymomas in discovery and validation cohorts using H3K27 acetylation ChIP-seq. Enhancer regions revealed novel oncogenes, molecular targets, and pathways, which when subjected to small molecule inhibitor or shRNA treatment, increased survival and halted proliferation in mouse and neurosphere patient-derived models of ependymomas. Reconstruction of enhancer networks permitted the identification of core transcription factors (TFs) that establish ependymoma cell state, and lineage-specifying TFs that dictate molecular subgroup identity. Lineage-associated TFs point to distinct spatio-temporal origins of ependymoma subgroups such as FOXJ1 TF activity and expression observed preferentially in subsets of hindbrain ependymomas. To translate our results into a potential clinical paradigm, we demonstrate cancer dependencies on super enhancer associated genes and lineage TFs, and establish the utility of chromatin landscape analysis to predict novel targets for cancer therapy.
IMMU-19. IMMUNE RESPONSE OF MOUSE HEDGEHOG MEDULLOBLASTOMA TREATED WITH SMOOTHENED INHIBITOR
Authors: Mai Dang, Kanika Jain, Chi Van Dang, Tom Curran, Malay Haldar
Journal: Neuro-Oncology (2017)

Sonic hedgehog subgroup medullloblastoma is driven by activation of the hedgehog pathway. This discovery presented the first opportunity for a treatment based on molecular-targeted therapy. Inhibition of the pathway by a small molecule, Smoothened inhibitor, arrests tumor cell proliferation and increases apoptosis in a medulloblastoma mouse model Ptch1+/- p53-/- resulting in elimination of even large spontaneous brain tumor. However, tumors eventually regrow and are resistant to the treatment, highlighting the need to further understand the tumor’s response to treatment which may reveal novel or combinatory treatment approaches. Toward this end, we questioned if the immune system plays a role in the tumor’s response to Smoothened inhibitor. In growing medulloblastoma of Ptch1+/- p53-/- mice, we found a significant infiltration of myeloid cells expressing IbaI, a marker of macrophages and microglial. More importantly, we discovered a dramatic increase of IbaI+ cells during tumor-regression induced by Smoothened inhibitor, GDC-0449. When tumors regress, ataxia resolves, and the cerebellar architecture appears to be restored. The dramatic increase in the amount of IbaI cells in tumors undergoing therapeutic regression suggests they have an important role in this treatment setting. Our current studies are focused on identifying if these macrophages are monocyte or microglia derived and if they play a role in tumor regression, restoration of the cerebellar architecture, or both.
Where does (sign) language begin?
Authors: Iris Berent, Amanda Dupuis
Journal: Behavioral and Brain Sciences (2017)

Abstract Goldin-Meadow &amp; Brentari (G-M&amp;B) outline several criteria for delineating the boundaries between (discrete) signs and (continuous) gestures. However, the complex links between linguistics forms and their phonetic realizations defy such heuristics. A systematic exploration of language structure by mouth and by hand may help get us closer to answering the important challenge outlined in this target article.
Nutritional Interventions for Mitochondrial OXPHOS Deficiencies: Mechanisms and Model Systems
Authors: Adam J. Kuszak, Michael Graham Espey, Marni J. Falk, Marissa A. Holmbeck, Giovanni Manfredi, Gerald S. Shadel, Hilary J. Vernon, Zarazuela Zolkipli-Cunningham
Journal: Annual Review of Pathology Mechanisms of Disease (2017)

Multisystem metabolic disorders caused by defects in oxidative phosphorylation (OXPHOS) are severe, often lethal, conditions. Inborn errors of OXPHOS function are termed primary mitochondrial disorders (PMDs), and the use of nutritional interventions is routine in their supportive management. However, detailed mechanistic understanding and evidence for efficacy and safety of these interventions are limited. Preclinical cellular and animal model systems are important tools to investigate PMD metabolic mechanisms and therapeutic strategies. This review assesses the mechanistic rationale and experimental evidence for nutritional interventions commonly used in PMDs, including micronutrients, metabolic agents, signaling modifiers, and dietary regulation, while highlighting important knowledge gaps and impediments for randomized controlled trials. Cellular and animal model systems that recapitulate mutations and clinical manifestations of specific PMDs are evaluated for their potential in determining pathological mechanisms, elucidating therapeutic health outcomes, and investigating the value of nutritional interventions for mitochondrial disease conditions.
Cyanine based Nanoprobes for Cancer Theranostics
Authors: Pravin Bhattarai, Zhifei Dai
Journal: Advanced Healthcare Materials (2017)

Cyanine dyes are greatly accredited in the development of non-invasive therapy that can "see" and "treat" tumor cells via imaging, photothermal and photodynamic treatment. However, these dyes suffer from poor pharmacokinetics inducing severe toxicity to normal cells, insufficient accumulation in tumor regions and rapid photobleaching when delivered in free forms. Nanoparticles engineered to encapsulate these compounds and delivering them into tumor regions have increased rapidly, however, so far, these nanoparticles (NPs) have not proved to be so effective to circumvent existing challenges. Newly designed multifunctional smart nanocarriers that can improve phototherapeutic properties of these dyes, co-encapsulate multiple potent therapeutic compounds, and simultaneously overcome limitations related to tumor recurrence, metastases, limited intracellular uptake, and tumor hypoxia have potential to revolutionize modern paradigm of cancer therapy. Such cyanine based multifunctional nanocarriers integrating imaging and therapy in a single platform can effectively produce better clinical outcomes in cancer treatment. This review briefly summarizes recent advancements of cyanine nanoprobes that are currently used as imaging/phototherapeutic agents in unimodal/bimodal/trimodal cancer theranostics. Finally, we conclude this review by addressing challenges of pre-existing therapeutic systems and designs adopted to overcome them with a brief insight assimilating future perspective of emerging cyanine-based NPs in cancer theranostics.
Sterilization in Man
Journal: BMJ (1966)

The technique results and considerations in vasectomy are discussed.  Vasectomy consists of uncoupling the duct leading from the testicle to the penis. 1-1 1/2 inches are cut out from the middle of the vas deferens.  The risk is minimal as it is simple surgery and the procedure can be done either in the hospital or the doctors office by a genitourinary surgeon or a general surgeon. In 99 cases out of 100 the sperm to the urethra is stopped after 2-3  weeks. Rare canalization of the vas always occurs within the 1st 6 months after the operation if it is to occur.  A mans coital performance remains unchanged;  the only effect on a mans virility is psychological. In a 1967 study by Ferber Tietze and Lewit 72 out of 73 American vasectomized men said they would have the operation again. 3 felt less satisfied with their sex lives after the  operation;  each had a preoperative potency problem that was aggravated.  Attempts to restore fertility have been successful 1/2 the time.  Experimental laboratories are working on methods for temporary vasectomy.
Histone Deacetylase Inhibitors Inhibit Metastasis By Restoring a Tumor Suppressive microRNA, Mir-150 in Advanced Cutaneous T-Cell Lymphoma
Authors: Akihiro Kitadate, Fumito Abe, Sho Ikeda, Junsuke Yamashita, Naoto Takahashi, Makoto Sugaya, Hiroyuki Tagawa
Journal: Blood (2016)
Abstract 13376: Oral Treatment With a Zinc Complex of Acetylsalicylic Acid Prevents Diabetic Cardiomyopathy in a Rat Model of Type 2 Diabetes
Authors: Sevil Korkmaz-Icöz, Samer Alsaid, Tamás Radovits, Shiliang Li, Mihály Ruppert, Paige Brlecic, Matthias Karck, Gábor Szabó
Journal: Circulation (2015)

Introduction: Type 2 diabetic patients are at an increased risk of cardiomyopathy and heart failure is a major cause of death amongst these patients. Growing evidence indicates that proinflammatory cytokines can cause sustained development of insulin resistance and anti-inflammatory medications may reverse this process. Hypothesis: We investigated the effects of an oral administration of zinc and acetylsalicylic acid in the form of bis(aspirinato)zinc(II) complex Zn(ASA)2 on different aspects of cardiac damage in the Zucker diabetic rat (ZDF), an experimental model of type 2 diabetic cardiomyopathy. Methods: The nondiabetic control and the diabetic ZDF rats were pretreated orally with vehicle or Zn(ASA)2 for 24 days. At the age of 30-32 weeks, both the electrical activity and the left ventricular (LV) structural/functional parameters were assessed via electrocardiogram and pressure volume (PV) conductance catheter system. Results: The Zn(ASA)2 treatment significantly decreased the blood glucose concentration (39.6±3.1 vs 50.4±2.6 mM), normalized the impaired LV contractility index (Emax 3.7±0.4 vs 1.9±0.6 mmHg/μl), the passive LV stiffness (end diastolic PV relationship: 0.064±0.008 vs 0.084±0.014 mmHg/μl), and the diastolic dysfunction (LV end diastolic pressure: 6.5±0.6 vs 7.9±0.7 mmHg). Furthermore, the ECG revealed a restoration of the prolonged corrected QT intervals (63±3 vs 83±4 ms, p&lt;0.05) by Zn(ASA)2. A histological examination revealed an increase in the cardiomyocytes transverse cross section area in diabetic rats compared to the controls, which was significantly decreased after Zn(ASA)2. Furthermore, a significant increase in fibrotic formation was observed in the diabetic rats compared to controls, and Zn(ASA)2 administration showed similar collagen content in the ZDF+Zn(ASA)2 rats and in the nondiabetics. A significant increase in the density of TUNEL positive cell nuclei in the diabetic hearts, indicating DNA fragmentation, was significantly decreased by Zn(ASA)2. Additionally, in the diabetic heart, Zn(ASA)2 significantly decreased nitrotyrosine formation. Conclusions: The oral administration of Zn(ASA)2 may have therapeutic potential with the aim of preventing cardiac complications in type 2 diabetic patients.
Irinotecan–temozolomide with temsirolimus or dinutuximab in children with refractory or relapsed neuroblastoma (COG ANBL1221): an open-label, randomised, phase 2 trial
Authors: Rajen Mody, Arlene Naranjo, Collin Van Ryn, Alice L Yu, Wendy B London, Barry L Shulkin, Marguerite T Parisi, Sabah-E-Noor Servaes, Mitchell B Diccianni, Paul M Sondel, Julia G Bender, John M Maris, Julie R Park, Rochelle Bagatell
Journal: The Lancet Oncology (2017)
Evaluation of physical examination elements in the diagnosis and prognosis of sports related concussion in adolescent athletes
Authors: Barry Willer, John Baker, Andrea Hinds, Jeff Miecznikowski, Natalie Czuczman, Kevin Lesh, John Leddy
Journal: British Journal of Sports Medicine (2017)

Objective To evaluate a brief physical examination (PE) for diagnosis and prognosis of sport-related concussion (SRC) in adolescents. Design Prospective. Setting UniversityConcussion clinics. Subjects 53 adolescents with SRC (mean age 15.4; 70% male) and 30 uninjured controls (mean age 15.8; 73% male). Interventions Participants received a brief PE (11 PE elements in three systems: cervical, oculomotor and vestibular). Concussed adolescents were assessed acutely (mean 4.5 days post-injury) and at follow up (mean 18.5 days). Outcome measures Dependent variables 1: Concussion versus uninjured and 2: Standard versus slow recovery (&gt;3 weeks). Recovery was defined as asymptomatic and exercise tolerant. Results Table 1 shows the significant PE variables that distinguished concussed from uninjured (via Fisher’s exact test; significance p&lt;0.05). Abstract 136 Table 1 PE elements (Visit 1) with 95% CI for Odds ratio and p-value Element CI p Neck tenderness (1.92, Inf) 0.00321 Smooth Pursuits (5.70, 786.21) &lt;0.00001 Convergence (1.10, 9.44) 0.03475 Abnormal saccades (3.34, 466.65) 0.00009 VOR (2.46, Inf) 0.00144 VOR Dizzy (3.67, Inf) 0.00015 Tandem gait (1.98, 291.60) 0.00191 Table 2 shows the significant PE variables distinguishing standard recovery from slow recovery at visit 2 (via Fisher’s exact test; significance p&lt;0.05). Abstract 136 Table 2 PE variables (Visit 2) with 95% CI for Odds ratio and p-value Neck spasm (1.13, Inf) 0.04148 Smooth pursuits (2.26, 127.15) 0.00298 Convergence (2.08, 53.74) 0.00319 Tandem gait (2.91, 773.79) 0.00105 Conclusions Easily administered physical exam reveals clinical findings that are important and sensitive for diagnosing acute concussion. Prognosis was less precise due to the heterogeneity of aetiology of slow recovery. Competing interests No competing interests for any authors.