tbuckley/cabot-search huggingface dataset:
Pyridyloxobutylated DNA adducts in oral mucosa of nonsmokers, smokers and snuff dippers in relation to other biomarkers of exposure
Authors: Anne-Kathrin Heling, Katharina Schutte-Borkovec, Christopher Heppel, Karl Fagerstrom, Elmar Richter
Journal: Cancer Research (2008)

1883  Pyridyloxobutylated (POB) DNA adducts releasing 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB) have been implicated in 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induced lung cancer and N’-nitrosonornicotine (NNN) induced esophageal tumors. However, biomonitoring studies of these adducts have not shown the expected specificity for smoking in either lung tissue or esophageal mucosa. NNK and NNN are also implicated in oral cancer of both smokers and snuff dippers. At present, the concept that currently available smokeless tobacco products (SLT) should be used as a substitute for cigarette smoking is controversely discussed. If at all, SLT should have low concentrations of NNN and NNK as is the case of Swedish snus. In the present study, POB DNA adduct were determined in buccal cells from 45 nonsmokers, 24 smokers, and 33 users of Swedish snus. Samples of oral mucosa were collected by Cytobrush Plus® from the left and right cheek, and from the site where snus was normally placed. Subjects filled in a questionnaire on smoking and dietary habits. Saliva and 1-2 mm clippings of the toenails were sampled for estimation of short- and long-term exposure to tobacco alkaloids. HPB-releasing adducts were determined after acid hydrolysis of DNA and derivatization by high-resolution gas chromatography/mass spectrometry with negative chemical ionization. Cotinine and myosmine in saliva and, together with nicotine, in toenails were determined by gas chromatography/mass spectrometry in the EI mode. Highly significant (p
COMP-03. TUMOR CONNECTOME: INSIGHT INTO THE IMPACT OF CNS NEOPLASIA AND THERAPY ON THE BRAIN NETWORK
Authors: Drew Parker, Jacob Alappatt, Mark Elliott, Steven Brem, Ragini Verma
Journal: Neuro-Oncology (2018)

Although surgical planning tools are aimed at avoiding damage to eloquent tracts, resection as well as treatment like radiation, may alter the structural connectivity of the whole brain. This may lead to subtle cognitive deficits in the future. The aim of this work is to present a paradigm to create a Tumor Evaluation Connectome, which is a map of the brain that shows how the regions are connected to each other. Although, connectomes are routinely used in various studies these days, it is extremely challenging to create one in the presence of tumor or a resection cavity. Thus a tumor connectome will enable the quantitative evaluation of structural connectivity between brain regions. The Tumor Evaluation Connectome was created as follows: the T1 images were parcellated into 153 anatomical regions, using multi-atlas tools. 119 gray matter regions were retained to build the connectome after the parcellations were manually assessed for mislabeling of unhealthy tissue. The DTI data was denoised, eddy and motion corrected. The anatomical labels in the T1 image were transferred to the DTI data, through a deformable registration method. 1 million streamlines were generated using deterministic tracking from mrtrix, seeded from voxels with fractional anisotropy exceeding 0.3. The Tumor Evaluation Connectome was defined with the 119 GM regions as nodes and the streamline count between them as the strength of the connection. These tumor connectomes will be used to generate network measures of deficit / change, as z-score from controls in the following pre-defined subnetworks: motor, visual, language, attention, memory, social cognition, cognitive control. CLINICAL IMPLICATIONS: Connectomes are an unmet need to refine tools for surgical planning, enhance recovery after brain tumor surgery, and assess the effects of therapeutic interventions is a specific, sensitive, and reproducible measure of the brain connectome.
Abstract 10903: Extraction Outcomes in Patients With Congenital Heart Disease
Authors: Erin A Fender, Ammar M Killu, David O Hodge, Bryan C Cannon, Paul A Friedman, Christopher J Mcleod, Craig S Broberg, Charles A Henrikson, Yong-Mei Cha
Journal: Circulation (2015)

Introduction: Patients with congenital heart disease (CHD) frequently require implantable cardiac devices. Device infection or malfunction may necessitate lead extraction. Extraction may be challenging due to long lead dwell times, anatomic abnormalities, and prior cardiac surgery. Little is known about extraction outcomes in the CHD population. Methods and Results: This retrospective study included 41 CHD patients and 82 age and gender matched controls that underwent lead extractions at two centers between 2001-2014. Only patients with leads older than 12 months were included. There were 79 leads in CHD patients and 150 in controls. Patients with CHD had a mean age of 39±17 years at extraction and on average their leads had been implanted for 81±84 months, this was not significantly different from the control group. Eighty eight percent of CHD patients had 1 or more cardiac surgeries as compared to only 22% of controls (p&lt;0.001). The number of abandoned leads was also significantly different with 16 abandoned leads in the CHD group and 3 in controls (p&lt;0.001). There was no statistically significant difference in extraction techniques between the groups. Complete extraction was achieved in 94% of patients in both groups. There were no CHD group complications. Control group complications included 3 SVC lacerations requiring sternotomy (one was fatal), and 1 ventricular perforations with tamponade requiring sternotomy. None of these patients had a history of cardiac surgery. The average age of leads in patients with a complication was 15.3 years which was older than the mean lead age seen in the CHD and control populations which was 6.75 and 4.6 years respectively. Conclusions: Lead extraction can be safely performed in patients with CHD. Despite anatomic abnormalities and previous cardiac surgery, the outcome of lead extraction in patients with CHD is comparable to controls. Prior cardiac surgery may lower the risk for extraction complications.
IMMU-15. ENGINEERED-DRUG RESISTANT GAMMA-DELTA (γδ) T CELLS COMBINED WITH IMMUNE CHECKPOINT BLOCKADE AUGMENTED KILLING OF CANCER CELLS
Authors: Sailesh Gopalakrishna Pillai, Yancey Gillespie, Cathy Langford, Samantha Langford, Trent Spencer, Lawrence S Lamb
Journal: Neuro-Oncology (2018)
Abstract 18999: The Evolution of Heart Failure Trials: 1986-Present
Authors: Matthew Bruce, Stephen Pickett, Steven Assalita, Wenyaw Chan, Biykem Bozkurt, Savitri Fedson, David Aguilar, Salim Virani, Christie Ballantyne, Anita Deswal, Vijay Nambi
Journal: Circulation (2017)

Introduction: Given changes in trial recruitment and advances in therapy for HF we evaluated if patient characteristics and their outcomes in contemporary HF randomized controlled trials (RCTs) hav...
Advancing toward the Elimination of Lymphatic Filariasis
Authors: David H. Molyneux
Journal: New England Journal of Medicine (2018)

The Global Program to Eliminate Lymphatic Filariasis (GPELF) was established in 2000 after the adoption of a World Health Assembly resolution in 1997 that called for member states of the World Health Organization (WHO) to eliminate lymphatic filariasis as a public health problem. The condition is caused by one of three filarial parasites. Wuchereria bancrofti, the most common of the three, causes 90% of lymphatic filariasis infections worldwide and is transmitted by several genera of mosquitoes — anopheles, aedes, mansonia, and culex. The strategy, known as preventive chemotherapy, is annual treatment by means of mass drug administration of a two-drug . . .
Human Papillomavirus Vaccination and School Entry Requirements
Authors: Ellen Daley, Erika Thompson, Gregory Zimet
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
Alcohol, Cigarette, and Cannabis Use Between 2002 and 2016 in Pregnant Women From a Nationally Representative Sample
Authors: Arpana Agrawal, Cynthia E. Rogers, Christina N. Lessov-Schlaggar, Ebony B. Carter, Shannon N. Lenze, Richard A. Grucza
Journal: JAMA Pediatrics (2018)

Public Health Implications of Rising Marijuana Use in Pregnancy in an Age of Increasing Legalization—Reply
TMIC-12. TUMOR-HOMING RNA-NANOPARTICLES REPROGRAM IMMUNE CELLS IN THE BRAIN TUMOR MICROENVIRONMENT
Authors: Adam Grippin, Hector Mendez-Gomez, Brandon Wummer, Tyler Wildes, Kyle Dyson, Daniel Valladares, Jon Dobson, Elias Sayour, Duane Mitchell
Journal: Neuro-Oncology (2018)

Brain tumors are particularly difficult to treat due to their relative isolation behind the blood brain barrier. Cytotoxic T cells elicited by cancer vaccines are capable of penetrating this barrier, but are limited by innate immune cells in tumor microenvironments that inhibit T cell function. There is therefore an unmet need for a method to reprogram the immune cells in the tumor microenvironment to promote antitumor T cell responses. We previously reported that systemically administered liposomes bearing RNA encoding tumor antigens profoundly activate innate immune cells in reticuloendothelial system (RES) organs. Here, we report a modified liposome formulation capable of redirecting this immunomodulatory nucleic acid cargo to immune cells in brain tumors. Cationic liposomes with varying compositions were loaded with Cy3-labelled RNA or siRNA and injected intravenously into glioma-bearing mice. RNA uptake was assessed with flow cytometry and immunofluorescence microscopy after 18 hours. Inclusion of cholesterol within liposomes increased mRNA uptake in intracranial GL261 and KR158b tumors after systemic injection in a dose-dependent manner. Optimized tumor-homing liposomes delivered mRNA encoding tumor antigens to CD45+ immune cells in both tumors. These liposomes were also used to deliver siRNA against programmed death ligand 1 (PDL1). siRNA-loaded liposomes reduced PDL1 expression on dendritic cells ex vivo and on transfected CD45+ cells in murine brain tumors. Our optimized liposomes effectively deliver mRNA and siRNA to immune cells in multiple murine brain tumors. Future work will consider the mechanism of this enhanced delivery and the use of tumor-homing liposomes to deliver other immunomodulatory biomolecules.
Endothelial Hypoxia-Inducible Factor-2α Is Required for the Maintenance of Airway Microvasculature
Authors: Xinguo Jiang, Wen Tian, Allen B. Tu, Shravani Pasupneti, Eric Shuffle, Petra Dahms, Patrick Zhang, Haoliang Cai, Thanh T. Dinh, Bo Liu, Corey Cain, Amato J. Giaccia, Eugene C. Butcher, M. Celeste Simon, Gregg L. Semenza, Mark R. Nicolls
Journal: Circulation (2019)

Hypoxia-inducible factors (HIFs), especially HIF-1α and HIF-2α, are key mediators of the adaptive response to hypoxic stress and play essential roles in maintaining lung homeostasis. Human and animal genetics studies confirm that abnormal HIF correlates with pulmonary vascular pathology and chronic lung diseases, but it remains unclear whether endothelial cell HIF production is essential for microvascular health. The large airway has an ideal circulatory bed for evaluating histological changes and physiology in genetically modified rodents.
Abstract 20885: Renal Denervation Prevents Cholinergic Mediated Hypertension and Renal Macrophage Infiltration
Authors: Sailesh C Harwani, Nandita S Raikwar, Jason A Ratcliff, Chantal Allamargot, Mark W Chapleau, Francois M Abboud
Journal: Circulation (2017)

In vivo cholinergic activation with nicotine induces renal infiltration of M1 inflammatory CD161a+/CD68+ macrophages and the development of hypertension. Renal denervation has been proposed as a treatment for essential hypertension. Based on this we hypothesized that the renal sympathetic nerves play a role in these processes. Bilateral renal denervation was performed surgically in 3-4 week old Spontaneously Hypertensive Rats (SHR), a genetic model of essential hypertension. Following one week recovery, animals received subcutaneous infusion of nicotine (15mg/kg/day) via osmotic pumps for 2 weeks. Blood pressure was measured by tail-cuff and kidneys harvested on completion of infusion. Prior to nicotine infusion, at baseline, there was no difference between the systolic blood pressures of the sham treated (n=7) and renal denervation (n=10) groups, 132 ± 4 vs 128 ± 3 mmHg, respectively (p>0.05). In contrast, nicotine infusion significantly raised the systolic blood pressure in the sham treated group (159 ±...
EPID-06. RACIAL DISPARITY IN THE SURGICAL MANAGEMENT OF SKULL BASE CHONDROSARCOMAS: A SURVEILLANCE, EPIDEMIOLOGY, AND END RESULTS (SEER) ANALYSIS
Authors: Sanjay Dhawan, Ali Alattar, Jiri Bartek, Jun Ma, Clark Chen
Journal: Neuro-Oncology (2018)

Surgical resection is a key aspect in the treatment paradigm for skull-base chondrosarcomas. Here, we examined the practice patterns in the surgical management of skull base chondrosarcomas using the Surveillance, Epidemiology, and End Results (SEER) database. We identified patients with skull-base chondrosarcomas in the SEER registry with available information on whether surgery was recommended. Clinical and demographic variables associated with increased odds of recommendation against surgery were analyzed using univariable and multivariable logistic regression. Of 493 patients with skull-base chondrosarcoma in SEER, 446 were recommended to undergo surgery by the treating physician and 38 were not. On univariate analysis, no significant differences were noted between these groups in terms of age, sex, marital status, size of tumor, tumor location, chemotherapy treatment, or radiation therapy treatment. The odds of recommendation against surgery were significantly higher in African Americans relative to Caucasians (OR=4.056, p=0.001). In a multivariate logistic regression model, the association between African American race and recommendation against surgery remained robust (OR 4.28, p=0.01) while the association with median income lost statistical significance (OR=0.966 per $1000 increase in income, p=0.083). This SEER analysis revealed notable racial disparity in terms of surgical recommendation for patients suffering from skull-base chondrosarcoma. The odds of recommendation against surgery were significantly higher in African American patients in a multivariate model that accounted for other available, pertinent variables.
CSIG-36. INVOLVEMENT OF microRNAs 221/222-3p IN THE REGULATION OF PROGRAMMED CELL DEATH 10 (PDCD10) GENE IN GLIOBLASTOMA
Authors: Nargis Malik, Parthaprasad Chattopadhyay, Chitra Sarkar, Ashish Suri, Subrata Sinha, Kunzang Chosdol
Journal: Neuro-Oncology (2018)

INTRODUCTION: FAT1 gene is localized at chromosome 4q35.2 encoding a 506KDa. Here in our study we are characterizing the role of FAT1 in primary brain tumors. MiR-221-3p/222-3p reported to have oncogenic role and targets tumor suppressors (e.g. PDCD10, PTEN, PUMA etc.) in many cancers including GBM. Here, we have analyzed the role of FAT1 gene in the regulation of miRNAs in GBM. METHODOLOGY: In-silico analysis of miR targets was done by target prediction software miRDB, TargetScan, miRTarBase. FAT1 knockdown was done using FAT1 specific siRNA and mRNA expression analysis done by gene specific primers and for miR-221/222-3p using LNA-primers in GBM cell lines (U87MG, U373MG, A172 and LN229). Expression and Spearman correlation analysis of FAT1 and miR-221-3p was done in GBM tumor samples (n=30). We have observed increased expression of FAT1 and miRNAs (miR221-3p/miR222-3p) in GBM cell lines (U87MG, U373MG, A172 & LN229). On FAT1 knockdown, by siFAT1 we observed significantly reduced expression of miR-221/222-3p. In-silico analysis identified, TIMP3, PDCD10, PUMA and PTEN as potential targets of miR-221/222-3p. Furthermore, FAT1 knocked-down cells showed significantly augmented expression of PDCD10 in all studied glioma cell lines. In order to validate our in-vitro observation and its clinical relevance, we have done expression and correlation study in GBM tumor samples. We observed significant positive spearman correlation between FAT1 and miR-221-3p (r=0.5669, p≤0.0011) and negative correlation of FAT1 with PDCD10 (r= -0.3492, p≤0.0585),) and miR-221-3p with PDCD10 (r=0.526, p≤0.0028). These results suggest that FAT1 expression positively regulates the expression of miR-221-3p leading to downregulation of miR 221-3p target (PDCD10) in GBM cell lines and GBM tumors. CONCLUSION: Taken together our in-vitro and GBM tumor data for the first time suggesting FAT1 to be a novel molecule regulating the expression of miRNA in GBM and FAT1 may emerge as a target for therapeutic intervention.
Familiar barriers still unresolved—a perspective on the Zika virus outbreak research response
Authors: Marion Koopmans, Xavier de Lamballerie, Thomas Jaenisch, Kerstin D Rosenberger, Ivonne Morales, Ernesto T A Marques, Isabelle F T Viana, Patricia Brasil, Renata Rabello, Vivian I Avelino-Silva, Aluisio Segurado, Neal Alexander, Philippe Mayaud, Eduardo Martins Netto, Adriana Tami, Sarah Bethencourt, Maria Consuelo Miranda, Anyela Lozano, Carmen Soria, Silvia Paula Salgado Cisneros, Eduardo Gotuzzo, María G Guzmán, Pedro A M Rodriguez, Hugo Lopez-Gatell, Jennifer Hegewisch-Taylor, Victor Hugo Borja-Aburto, Cesar Gonzales Bonilla, Bruno Hoen, Martine van Roode, Barry Rockx
Journal: The Lancet Infectious Diseases (2018)
CBMT-15. METABOLIC AND TRANSCRIPTIONAL PROFILES OF GBM INVASION: COMPARISON OF PATIENTS AND PAIRED PATIENT DERIVED XENOGRAFTS USING1H MAGNETIC RESONANCE SPECTROSCOPY AND IMAGING (7T AND 14T) AND RNA-SEQUENCING
Authors: Monika Hegi, Cristina Cudalbu, Pierre Bady, Marta Lai, Lijing Xin, Olga Gusyatiner, Marie-France Hamou, Mario Lepore, Roy Daniel, Rolf Gruetter, Andreas Hottinger
Journal: Neuro-Oncology (2018)

Glioblastoma (GBM) are notorious for their invasive behavior. Little is known about the biology of the tumor cells and the microenvironment at the invasive front that is highly relevant for recurrence. These cells are technically difficult to visualize, lie usually outside the resected and irradiated area, and are behind the blood brain barrier that renders them difficult to treat. We present patient specific metabolic and transcriptomic features of invasive growth using corresponding patient derived xenografts (PDX). Patients with suspected GBM were enrolled and underwent 1H magnetic resonance spectroscopy and imaging (1H-MRS/I) at 7 Tesla. Tissue obtained at the subsequent resection was dissociated and transplanted orthotopically into mice (n=4 to 6). Mice were followed longitudinally by 1H-MRS/I (14T). The PDX, the corresponding tissue of the contralateral side, and the original tumors were subjected to RNA sequencing. Tumor versus host (mouse) derived sequencing reads are computationally separated. Diffuse xenografts developed for 8 (IDHwt) of 9 patients within 2–5 months. 1H-MRS at ultrahigh fields allowed reliable quantification of 22 metabolites. The temporal changes of the metabolite signatures characterized the kinetics of invasive growth on both, the injected and the contralateral side. At end stage the signatures corresponded well with histological findings. Migration to the contralateral side ranged in a patient dependent manner between < 1 to > 50% 50% of tumor cells. Comparison of MRS derived metabolite signatures at end stage and the corresponding human signatures compared best with voxels measured outside the core of the human tumor. Associations between the metabolite signatures and the transcriptome in the xenografts and the host will be discussed. CONCLUSION: Integration of metabolic profiles and gene expression of the tumor and the invaded brain may provide insights and tools for in vivo monitoring of treatment response in the infiltration zone. GRANTS: Swiss Bridge Award, Swiss Cancer Ligue
CBMT-33. ALTERNATING ELECTRIC FIELDS INDUCED BY FAST SPINNING STRONG MAGNETS MODULATE MITOCHONDRIAL ENERGY METABOLISM IN GBM CELLS
Authors: Kumar Pichumani, Omkar Ijare, Martyn Sharpe, David Baskin, Santosh Helekar
Journal: Neuro-Oncology (2018)

Recently, scalp application of alternating electric fields has shown therapeutic benefit in patients with glioblastoma multiforme (GBM). The U.S. Food and Drug Administration has approved this new “Tumor Treating Fields (TTF)” therapy provided by Novocure (trade name Optune) as monotherapy for recurrent GBM and in combination with temozolomide for newly diagnosed GBM. Two multicenter Phase III clinical trials demonstrate that in the former condition TTF treatment after standard of care chemotherapy only increases median survival from 6 to 6.6 months, and in the latter condition combination chemo-TTF therapy, compared to chemotherapy alone, prolongs progression free survival from 4 to 7.1 months. Although this treatment is highly promising, its underlying biophysical and molecular mechanisms are unclear. “Transcranial Rotating Permanent Magnet Stimulation” (TRPMS) is a similar approach in which non-invasive multifocal magnetic stimulation produces the required alternating electric fields by electromagnetic induction. Ongoing pilot TRPMS trials in chronic ischemic stroke and other neurological patients reveal a complete absence of significant TRPMS device-related adverse effects. Here, we report pre-clinical tests of the hypothesis that TRPMS-based alternating electric fields cause depolarization of the mitochondrial membrane potential (MMP) and alter mitochondrial oxidation of nutrients, leading to reactive oxygen species (ROS) and cytochrome C-mediated apoptosis in patient-derived GBM cells. Using 13C NMR spectroscopybased isotopomer analysis in GBM cells we observe that after 3 hours of treatment with TRPMS-induced electric field stimulation there is an increased metabolic flux of glycolysis and decreased mitochondrial glucose oxidation in the TCA cycle. Fluorescence microscopy with MitoTracker demonstrates changes in staining intensity that are consistent with TRPMS-induced disruption of mitochondrial networks due to depolarization of MMP, processes that culminate in apoptosis triggered by release of ROS and cytochrome C. These findings, if supported by in-vivo data in mouse models, would suggest an important role of TRPMS in GBM treatment.