tbuckley/cabot-search huggingface dataset:
Abstract 5362: Targeting BRCA1 and BRCA2 with NEBNext Direct™
Authors: Scott M. Adams, Kruti M. Patel, Amy B. Emerman, Sarah K. Bowman, Charles D. Elfe, Noa Henig, Salvatore Russello, Andrew Barry, Theodore Davis, Cynthia L. Hendrickson
Journal: Cancer Research (2017)

Abstract The screening and detection of germline BRCA1 and BRCA2 mutations are critical for the effective management of patients with breast or ovarian cancer and for the identification of individuals with a high risk of developing these cancers. In addition, somatic detection of pathogenic variants in BRCA1/2 can influence treatment decisions due to the susceptibility of tumors with BRCA mutations to PARP inhibitors. Here we introduce the NEBNext DirectTM BRCA enrichment panel for the interrogation of BRCA1 and BRCA2 by Illumina sequencing. NEBNext DirectTM is a novel, hybridization-based method to selectively enrich nucleic acid targets ranging from a single gene to several hundred genes. This approach includes features such as the incorporation of unique molecule identifiers (UMIs) and the ability to capture degraded DNA, enabling accurate detection of low-frequency variants from formalin-compromised DNA and other challenging sample types. We applied the NEBNext Direct BRCA1/2 panel to frozen tissue and achieved a high specificity for the BRCA targets (96% of the sequenced reads mapped to BRCA1 and BRCA2 and 80% of the sequenced bases were within the targeted regions). In addition, the resulting libraries were highly uniform in coverage, with 91% of the targeted bases covered at a value of at least 50% of the mean depth of coverage and 100% of the bases covered at 20% of the mean or greater. Some variability in the specificity was observed with formalin-fixed, paraffin embedded (FFPE) samples, and this effect was dependent on the quality of the FFPE DNA. The UMIs were used to identify PCR duplicates prior to variant calling, as well as for error correction, enabling the accurate detection of low-frequency variants. The library preparation for all samples was completed in one day, and the entire process of library preparation, sequencing on the Illumina Miseq, and data analysis was completed in a total of two days. In summary, we demonstrate that application of the NEBNext DirectTM method to the enrichment of BRCA1 and BRCA2 provides a tractable approach for the rapid and highly sensitive analysis of these cancer-associated genes. Citation Format: Scott M. Adams, Kruti M. Patel, Amy B. Emerman, Sarah K. Bowman, Charles D. Elfe, Noa Henig, Salvatore Russello, Andrew Barry, Theodore Davis, Cynthia L. Hendrickson. Targeting BRCA1 and BRCA2 with NEBNext Direct™ [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5362. doi:10.1158/1538-7445.AM2017-5362
Concept of Alexithymia
Authors: Liisa Keltikangas-Järvinen
Journal: Psychotherapy and Psychosomatics (1985)

The prevalence of alexithymia was studied in a psychosomatic group consisting of 34 patients with duodenal ulcer, 35 patients with ulcerative colitis and 38 patients with irritable colon syndrome, and in a control group consisting of 29 patients with gallstone disease, 13 patients with inguinal hernia and 44 patients with varicose veins. The methods used were the Beth Israel Hospital Questionnaire, the Thematic Apperception Test, the Rorschach Test and the score of emotionality derived from Lazare's Test. The results showed that alexithymia can be detected in an unselected sample of psychosomatic patients. The social class was of no significance, but a high score of alexithymia was registered for the male psychosomatic patients.
Autoreactive T cells in type 1 diabetes
Authors: Alberto Pugliese
Journal: Journal of Clinical Investigation (2017)

Type 1 diabetes (T1D) is a chronic autoimmune disease that causes severe loss of pancreatic β cells. Autoreactive T cells are key mediators of β cell destruction. Studies of organ donors with T1D that have examined T cells in pancreas, the diabetogenic insulitis lesion, and lymphoid tissues have revealed a broad repertoire of target antigens and T cell receptor (TCR) usage, with initial evidence of public TCR sequences that are shared by individuals with T1D. Neoepitopes derived from post-translational modifications of native antigens are emerging as novel targets that are more likely to evade self-tolerance. Further studies will determine whether T cell responses to neoepitopes are major disease drivers that could impact prediction, prevention, and therapy. This Review provides an overview of recent progress in our knowledge of autoreactive T cells that has emerged from experimental and clinical research as well as pathology investigations.
Abstract 1737: ALK rearrangement analysis in circulating tumor cells of lung cancer patients
Authors: Min Kyung Jeon, Young Hun Kim, Eunjoo Hwang, Hye Seon Lee, Ji-hyun Uh, Myoung Shin Kim, JooKyung Park, Byung Hee Jeon, Se-Hoon Lee
Journal: Cancer Research (2017)

Abstract The evaluation of ALK rearrangement in non-small-cell lung cancer (NSCLC) is a significant tool when considering chemotherapy. It is not always possible to perform a tumor biopsy in patients. We suggest isolation and culturing of circulating tumor cells (CTCs) as an alternative tool to a tumor biopsy for the diagnosis of ALK rearrangement. From 22 patients with NSCLC harboring ALK rearrangement, blood samples were collected and divided into two parts: one for immunofluorescence staining of CTC marker and the other for culturing of CTCs. Both samples were processed by size-based filtration, and Cultured CTCs were analyzed for EML4-ALK translocation by fluorescence in situ hybridization (FISH) using Vysis ALK break apart FISH probe kit. CTC culturing was successful in 18 of 22 cases (81.8%). Among 18 cases of successful CTC cultures, 13 cases showed ALK rearrangement positivity (72.2%). Therefore, we suggest that the CTCs can be used as an alternative method to tissue biopsy for diagnosing ALK rearrangement. In addition, this method may have clinical applications including serial blood sampling for the development of personalized cancer therapy based on individual genomic information. Citation Format: Min Kyung Jeon, Young Hun Kim, Eunjoo Hwang, Hye Seon Lee, Ji-hyun Uh, Myoung Shin Kim, JooKyung Park, Byung Hee Jeon, Se-Hoon Lee. ALK rearrangement analysis in circulating tumor cells of lung cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1737. doi:10.1158/1538-7445.AM2017-1737
Hematopoietic Architecture of MDS before and after Progression Reveals Two Biologically Distinct Disease Subtypes
Authors: Irene Gañán-Gómez, Ana Alfonso, Yamini Ogoti, Hui Yang, Guillermo Montalban-Bravo, Abraham C Yu, Matteo Marchesini, Carlos E Bueso-Ramos, Koichi Takahashi, Karen Clise-Dwyer, Guillermo Garcia-Manero, Simona Colla
Journal: Blood (2016)
Circular RNAs: Regulators of Cancer-Related Signaling Pathways and Potential Diagnostic Biomarkers for Human Cancers
Authors: Zuozhang Yang, Lin Xie, Lei Han, Xin Qu, Yihao Yang, Ya Zhang, Zewei He, Yu Wang, Jing Li
Journal: Theranostics (2017)

Circular RNAs (circRNAs) are newly discovered endogenous non-coding RNAs featuring structural stability, high abundance, and tissue-specific expression.CircRNAs are prevalent and conserved in mammalian cells.They are involved in cellular processes and regulate gene expression at the transcriptional or post-transcriptional level by interacting with microRNAs (miRNAs) and other molecules.Recent studies have shown that circRNAs play an important role in the progression of various human diseases including atherosclerosis, nervous system disorders, diabetes, and cancer.In this review, we summarize the advances on endogenous circRNAs in eukaryotic cells and elucidate their diagnostic and prognostic significance in human cancers.Especially, we highlight the involvement of circRNAs in signal transduction pathways as well as their clinical potential to serve as biomarkers.
Doctor and MPs in Italy are assaulted after vaccination law is passed
Authors: Michael Day
Journal: BMJ (2017)

A doctor and three MPs have been assaulted after protests in Italy against legislation requiring parents to vaccinate their children against 10 diseases by school age.

After the law passed through Italy’s lower house of parliament on Friday 28 July, anti-vaccine demonstrators assaulted three MPs outside the parliament building in Rome. The three parliamentarians—Elisa Mariano, Ludovico Vico, and Salvatore Capon of the ruling centre-left Democratic Party—were rescued by police officers from a mob shouting “killers.”

On 31 July it emerged that a man …
Numerical magnitude evaluation as a foundation for decision making
Authors: Christopher Y Olivola, Nick Chater
Journal: Behavioral and Brain Sciences (2017)

The evaluation of magnitudes serves as a foundation not only for numerical and mathematical cognition, but also for decision making. Recent theoretical developments and empirical studies have linked numerical magnitude evaluation to a wide variety of core phenomena in decision making and challenge the idea that preferences are driven by an innate, universal, and stable sense of number or value.
The Importance of a Valid Comparison Group
Authors: Natalie Mota, Jessica Enns, Laurence Y. Katz
Journal: JAMA Psychiatry (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 Psychiatry 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 Psychiatry journal
Quantitative liver MRI including extracellular volume fraction for non-invasive quantification of liver fibrosis: a prospective proof-of-concept study
Authors: Julian A Luetkens, Sabine Klein, Frank Traeber, Frederic C Schmeel, Alois M Sprinkart, Daniel L R Kuetting, Wolfgang Block, Kanishka Hittatiya, Frank E Uschner, Robert Schierwagen, Juergen Gieseke, Hans H Schild, Jonel Trebicka, Guido M Kukuk
Journal: Gut (2017)

We read with interest the recent reviews published in Gut , emphasising that even though the understanding of the pathobiology of liver fibrosis has been improved in the last three decades,1 novel and easy to implement diagnostic and therapeutic approaches are required.2 Indeed, fibrosis is the most important histological feature of patients with chronic liver disease (CLD), such as non-alcoholic fatty liver disease, and is associated with long-term overall mortality, liver transplantation and liver-related events.3 Diagnostic and therapeutic approaches,2 therefore, require accurate measurements that ideally allow non-invasive fibrosis quantification, representing the whole liver free of bias and easily integrated in clinical routine.

A liver biopsy, still the reference standard, has substantial drawbacks (complications, intraobserver and interobserver variabilities).4 Transient elastography (TE), suggested for population-wide screens (eg, patients with diabetes),5 requires additional expensive devices and trained personnel. However, contrast-enhanced MRI is routinely performed and recommended in patients with CLD for exclusion of hepatocellular …
From continuous magnitudes to symbolic numbers: The centrality of ratio
Authors: Pooja G. Sidney, Clarissa A. Thompson, Percival G. Matthews, Edward M. Hubbard
Journal: Behavioral and Brain Sciences (2017)

Leibovich et al.'s theory neither accounts for the deep connections between whole numbers and other classes of number nor provides a potential mechanism for mapping continuous magnitudes to symbolic numbers. We argue that focusing on non-symbolic ratio processing abilities can furnish a more expansive account of numerical cognition that remedies these shortcomings.
Abstract 16017: A Low Burden Mouse Auricle Model for Venous Research
Authors: Caroline Arnold, Larissa Pfisterer, Markus Hecker, Thomas Korff
Journal: Circulation (2016)

Venous diseases such as deep vein thrombosis or chronic venous insufficiency constitute a substantial cause of morbidity in the western world. Although most of these diseases originate from varicose vein formation, animal models mimicking their development are scarce. Venous valve failure, pregnancy or obesity pose as main risk factors for varicose vein development due to impaired venous return and therefore increased venous filling pressure. Hence, we hypothesized that experimental venous hypertension is sufficient to elicit corresponding detrimental remodeling processes. To this end, we invented a model to evoke venous hypertension by occluding one large vein in the mouse auricle resulting in enhanced tortuosity and growth (~2.5-fold, p
Abstract 1131: O-GlcNAc transferase inhibition in breast cancer cells
Authors: Anna Barkovskaya, Lina Prasmickaite, Damien Y. Duveau, Ian G. Mills, Gunhild M. Mælandsmo, Siver A. Moestue, Harri M. Itkonen
Journal: Cancer Research (2017)

Abstract O-linked-N-acetylglucosamination (O-GlcNAcylation) is a post-translational modification that occurs on serine and threonine amino acid residues of the intracellular proteins. O-GlcNAcylation of numerous targets is catalyzed by a single enzyme - O-GlcNAc-transferase (OGT). O-GlcNAcylation impacts protein activation and stability thereby regulating several key biological functions, and is heavily involved in cancer development and progression. OGT expression and total protein O-GlcNAcylation are elevated in many cancers compared to non-malignant adjacent tissues. In breast cancer, this increase also has a positive correlation with the tumor grade suggesting a possible link to metastasis and disease progression. Here we investigated the effects of OGT inhibition in two triple-negative (TNBC) and two receptor-positive luminal breast cancer cell lines. Treatment of cells with an OGT inhibitor as well as OGT knockdown led to a strong decrease in viability and proliferation of the TNBC cells, but significantly less so in the luminal receptor-positive cell lines. This differential response was evaluated using analysis of apoptosis, cell cycle, gene expression and a reverse-phase antibody-based protein array (RPPA). We found that cell cycle progression was affected by OGT inhibition. In addition, proteomics data pointed towards the transcription factor hairy and enhancer of split-1 (HES1) as a possible mediator of the cytotoxicity observed in the TNBC cell lines. We currently work to elucidate the molecular mechanisms of HES1 regulation by OGT and its effect on TNBC cell survival and apoptosis. In conclusion, OGT inhibition has a pronounced cytotoxic effect on the TNBC cells and may have some potential for therapeutic use in the future. Citation Format: Anna Barkovskaya, Lina Prasmickaite, Damien Y. Duveau, Ian G. Mills, Gunhild M. Mælandsmo, Siver A. Moestue, Harri M. Itkonen. O-GlcNAc transferase inhibition in breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1131. doi:10.1158/1538-7445.AM2017-1131
Abstract 4161: Increased expression of ABCB1 could be associated with osimertinib resistance in non-small cell lung cancer cell line PC9 cell
Authors: Takashi Nomizo, Hiroaki Ozasa, Takahiro Tsuji, Yuto Yasuda, Tomoko Funazo, Hironori Yoshida, Yuichi Sakamori, Hiroki Nagai, Young Hak Kim
Journal: Cancer Research (2017)

Abstract Osimertinib, a third-generation EGFR Tyrosine kinase inhibitor, has shown promising activity in EGFR mutation positive non-small cell lung cancer (NSCLC) which harboring T790M mutation. The mechanisms of resistance to osimertinib have been still unclear. To investigate the mechanisms of acquired resistance to osimertinib, we established the osimertinib-resistant cell line (PC9/osimertinib) from the NSCLC cell lines PC9, and measured the expression levels of ATP-binding cassette (ABC) transporters using quantitative real-time polymerase chain reaction. Expression profiling of ABC transporters revealed that the levels of ABCB1 gene expression were significantly increased in the PC9/osimertinib cells compared with the parental cells, but not other ABC transporters. Knockdown of ABCB1 expression using short hairpin RNA enhanced osimertinib cytotoxicity in PC9/osimertinib cells. These data suggest that increased expression of ABCB1 may have an important role in the acquired resistance to osimertinib. Citation Format: Takashi Nomizo, Hiroaki Ozasa, Takahiro Tsuji, Yuto Yasuda, Tomoko Funazo, Hironori Yoshida, Yuichi Sakamori, Hiroki Nagai, Young Hak Kim. Increased expression of ABCB1 could be associated with osimertinib resistance in non-small cell lung cancer cell line PC9 cell [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4161. doi:10.1158/1538-7445.AM2017-4161
Abstract 5818: Disrupting the Aurora kinase A interactome in pediatric cancer
Authors: Sucheta Mukherjee, Carolyn Tu, Clay Gustafson
Journal: Cancer Research (2017)

Abstract Neuroblastoma is the most common extra-cranial solid tumor of childhood. Amplification of the MYCN proto-oncogene occurs in 50% of the high-risk neuroblastoma and indicates an aggressive and lethal form of the disease. As a transcription factor with no apparent small-molecule surfaces, direct inhibition of MYCN has proven challenging. Proteolytic cleavage of MYCN is regulated in part by an activity-independent scaffold function of Aurora Kinase A (AURKA). The dynamic expression and activation of AURKA allows for precise cell cycle regulation of several substrates identified by protein-protein interaction studies that are also viable anti-cancer targets, such as the aforementioned MYCN oncoprotein. Utilizing co-immunopreciptation, flow cytometry, and other pertinent cell biology techniques, we aim to delineate a novel mechanism of targeting the AURKA interactome by conformation disruption of AURKA. We have recently described a neoteric class of confirmation disrupting “amphosteric” inhibitors of AURKA (CD-AURKAi) that orthosterically inhibit the ATP-binding pocket to dramatically disrupt the active conformation of AURKA to dissociate and degrade MYCN, a critical oncogenic driver of the pediatric cancer neuroblastoma. In addition to MYCN, our preliminary results show CD532 will also dissociate other oncogenic proteins that interact with AURKA. We hypothesize that conformation disruption of AURKA and subsequent blockade of an array of protein-protein interactions will delineate the roles of AURKA, MYC, and MYCN in the cell cycle and expand the clinical applications for CD-AURKAi in cancer to include non-MYCN driven diseases. Citation Format: Sucheta Mukherjee, Carolyn Tu, Clay Gustafson. Disrupting the Aurora kinase A interactome in pediatric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5818. doi:10.1158/1538-7445.AM2017-5818
Al<sup>18</sup>F-Labeling Of Heat-Sensitive Biomolecules for Positron Emission Tomography Imaging
Authors: Frederik Cleeren, Joan Lecina, Muneer Ahamed, Geert Raes, Nick Devoogdt, Vicky Caveliers, Paul McQuade, Daniel J Rubins, Wenping Li, Alfons Verbruggen, Catarina Xavier, Guy Bormans
Journal: Theranostics (2017)

Positron emission tomography (PET) using radiolabeled biomolecules is a translational molecular imaging technology that is increasingly used in support of drug development.Current methods for radiolabeling biomolecules with fluorine-18 are laborious and require multistep procedures with moderate labeling yields.The Al 18 F-labeling strategy involves chelation in aqueous medium of aluminum mono[ 18 F]fluoride ({Al 18 F} 2+ ) by a suitable chelator conjugated to a biomolecule.However, the need for elevated temperatures (100-120 °C) required for the chelation reaction limits its widespread use.Therefore, we designed a new restrained complexing agent (RESCA) for application of the AlF strategy at room temperature.Methods.The new chelator RESCA was conjugated to three relevant biologicals and the constructs were labeled with {Al 18 F} 2+ to evaluate the generic applicability of the one-step Al 18 F-RESCA-method.Results.We successfully labeled human serum albumin with excellent radiochemical yields in less than 30 minutes and confirmed in vivo stability of the Al 18 F-labeled protein in rats.In addition, we efficiently labeled nanobodies targeting the Kupffer cell marker CRIg, and performed µPET studies in healthy and CRIg deficient mice to demonstrate that the proposed radiolabeling method does not affect the functional integrity of the protein.Finally, an affibody targeting HER2 (PEP04314) was labeled site-specifically, and the distribution profile of (±)-[ 18 F]AlF(RESCA)-PEP04314 in a rhesus monkey was compared with that of [ 18 F]AlF(NOTA)-PEP04314 using whole-body PET/CT.Conclusion.This generic radiolabeling method has the potential to be a kit-based fluorine-18 labeling strategy, and could have a large impact on PET radiochemical space, potentially enabling the development of many new fluorine-18 labeled protein-based radiotracers.