tbuckley/cabot-search huggingface dataset:
Genomic Correlates of Disease Progression and Treatment Response in Prospectively Characterized Gliomas
Authors: Philip Jonsson, Andrew L. Lin, Robert J. Young, Natalie M. DiStefano, David M. Hyman, Bob T. Li, Michael F. Berger, Ahmet Zehir, Marc Ladanyi, David B. Solit, Angela G. Arnold, Zsofia K. Stadler, Diana Mandelker, Michael E. Goldberg, Juliann Chmielecki, Maryam Pourmaleki, Shahiba Q. Ogilvie, Shweta S. Chavan, Andrew T. McKeown, Malbora Manne, Allison Hyde, Kathryn Beal, T. Jonathan Yang, Craig P. Nolan, Elena Pentsova, Antonio Omuro, Igor T. Gavrilovic, Thomas J. Kaley, Eli L. Diamond, Jacqueline B. Stone, Christian Grommes, Adrienne Boire, Mariza Daras, Anna F. Piotrowski, Alexandra M. Miller, Philip H. Gutin, Timothy A. Chan, Viviane S. Tabar, Cameron W. Brennan, Marc Rosenblum, Lisa M. DeAngelis, Ingo K. Mellinghoff, Barry S. Taylor
Journal: Clinical Cancer Research (2019)

Abstract Purpose: The genomic landscape of gliomas has been characterized and now contributes to disease classification, yet the relationship between molecular profile and disease progression and treatment response remain poorly understood. Experimental Design: We integrated prospective clinical sequencing of 1,004 primary and recurrent tumors from 923 glioma patients with clinical and treatment phenotypes. Results: Thirteen percent of glioma patients harbored a pathogenic germline variant, including a subset associated with heritable genetic syndromes and variants mediating DNA repair dysfunctions (29% of the total) that were associated with somatic biallelic inactivation and mechanism-specific somatic phenotypes. In astrocytomas, genomic alterations in effectors of cell-cycle progression correlated with aggressive disease independent of IDH mutation status, arose preferentially in enhancing tumors (44% vs. 8%, P &amp;lt; 0.001), were associated with rapid disease progression following tumor recurrence (HR = 2.6, P = 0.02), and likely preceded the acquisition of alkylating therapy-associated somatic hypermutation. Thirty-two percent of patients harbored a potentially therapeutically actionable lesion, of whom 11% received targeted therapies. In BRAF-mutant gliomas, response to agents targeting the RAF/MEK/ERK signaling axis was influenced by the type of mutation, its clonality, and its cellular and genomic context. Conclusions: These data reveal genomic correlates of disease progression and treatment response in diverse types of glioma and highlight the potential utility of incorporating genomic information into the clinical decision-making for patients with glioma.
Abstract 17338: Effect of Intracoronary Thrombus Burden on Microvascular Dysfunction After Primary Percutaneous Coronary Intervention; a Prospective Trial Assessed With Index of Microcirculatory Resistance
Authors: Hye Young Lee, Jeong Hoon Kim, Choong Won Goh, Kun Joo Rhee, Ji Min Chang, Euisuk Chung, Chul Kim, Hee Eun Choi, Byung Ok Kim
Journal: Circulation (2013)

INTRODUCTION: Aspiration thrombectomy (AT) has been advocated for ST-segment-elevation myocardial infarction (STEMI) and known to improve myocardial dysfunction after percutaneous coronary interven...
Abstract 13183: Dual Antiplatelet Therapy in Patients With Aspirin Resistance Following Coronary Artery Bypass Grafting
Authors: Hrvoje Gasparovic, Mate Petricevic, Tomislav Kopjar, Zeljko Djuric, Lucija Svetina, Bojan Biocina
Journal: Circulation (2013)

Background: Coronary artery bypass grafting (CABG) is pivotal in the contemporary management of complex coronary artery disease. Interpatient variability to antiplatelet agents, however, harbors po...
Photodynamic Therapy for the Treatment of Vertebral Metastases: A Phase I Clinical Trial
Authors: Carl Fisher, Zakariya Ali, Jay Detsky, Arjun Sahgal, Elizabeth David, Monica Kunz, Margarete Akens, Edward Chow, Cari Whyne, Shane Burch, Brian C. Wilson, Albert Yee
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Vertebroplasty (VP) and balloon kyphoplasty (KP) are minimally invasive stabilization procedures for pathologic vertebral compression fractures (VCF). Concurrent administration of photodynamic therapy (PDT) as a tumor-ablative modality has yet to be studied in humans as a potential complement to improved mechanical stability that is afforded by vertebral cement augmentation (VCA). Patients and Methods: This first-in-human trial used a single 6 mg/m2 dose of the clinical photosensitizer Visudyne with escalating laser light doses. Following a cohort of light-only controls (n = 6), the drug and light treatment groups (n = 6 each) were 50, 100, 150, and 200 J/cm. VCA was performed within 15 minutes following PDT. Patients were clinically reviewed at 1 and 6 weeks. The primary outcome measure was safety from a neurologic perspective. Results: Thirty patients comprising a variety of primary tumors were treated with PDT and either KP or VP. Vertebral PDT was technically feasible and delivered in all study patients. No dose groups showed significant increases in pain as defined by the generic SF-36 as well as disease-specific EORTC-QLQ-BM22 and EORTC-QLQ-C15-PAL questionnaires. The 50 and 100 J/cm groups showed the most significant pain reduction (P &amp;lt; 0.05). Twelve (40%) patients experienced complications during the study including 3 patients with further vertebral fracture progression by 6 weeks despite VCA. No complications were directly attributed to PDT. Conclusions: Using the parameters described, vertebral PDT as an adjunct to VCA is safe from a pharmaceutical and neurologic perspective. The results of this trial motivate scale-up study evaluating potential PDT efficacy in vertebral metastatic treatment.
Неалкогольна жирова хвороба печінки та артеріальна гіпертензія: патогенетичні чинники формування та прогресування
Authors: L.M. Pasiyeshvili, N.M. Zheleznyakova, T.M. Pasiyeshvili
Journal: GASTROENTEROLOGY (2014)

Поєднаний перебіг найбільш поширених та соціально значущих захворювань внутрішніх органів, таких як артеріальна гіпертензія (АГ) та неалкогольна жирова хвороба печінки (НАЖХП), може призводити до змін у патогенетичних ланках захворювань. У такому разі метою роботи було визначення механізмів формування та прогресування АГ у хворих на НАЖХП. До роботи було залучено 36 хворих із поєднанням АГ та НАЖХП та 21 пацієнт з ізольованою АГ. Визначали вміст інтерлейкінів-1, -2, -4, -6 та -8, циркулюючих імунних комплексів, суму показника системи комплементу й рівень автосенсибілізації лімфоцитів до власних антигенів. Установлено, що поєднаний перебіг АГ та НАЖХП призводить до змін в імунологічному спектрі крові, що характеризуються збільшенням показників запального процесу (прозапальних цитокінів, сумарного значення системи комплементу), що сприяє формуванню стеатогепатиту. Тобто при поєднаному перебігу АГ та НАЖХП виникають передумови прогресування патологічного процесу, мішенями якого є серце, нирки та печінка.
Identification of monocyte-like precursors of granulocytes in cancer as a mechanism for accumulation of PMN-MDSCs
Authors: Jérôme Mastio, Thomas Condamine, George Dominguez, Andrew V. Kossenkov, Laxminarasimha Donthireddy, Filippo Veglia, Cindy Lin, Fang Wang, Shuyu Fu, Jie Zhou, Patrick Viatour, Sergio Lavilla-Alonso, Alexander T. Polo, Evgenii N. Tcyganov, Charles Mulligan, Brian Nam, Joseph Bennett, Gregory Masters, Michael Guarino, Amit Kumar, Yulia Nefedova, Robert H. Vonderheide, Lucia R. Languino, Scott I. Abrams, Dmitry I. Gabrilovich
Journal: The Journal of Experimental Medicine (2019)

We have identified a precursor that differentiates into granulocytes in vitro and in vivo yet belongs to the monocytic lineage. We have termed these cells monocyte-like precursors of granulocytes (MLPGs). Under steady state conditions, MLPGs were absent in the spleen and barely detectable in the bone marrow (BM). In contrast, these cells significantly expanded in tumor-bearing mice and differentiated to polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Selective depletion of monocytic cells had no effect on the number of granulocytes in naive mice but decreased the population of PMN-MDSCs in tumor-bearing mice by 50%. The expansion of MLPGs was found to be controlled by the down-regulation of Rb1, but not IRF8, which is known to regulate the expansion of PMN-MDSCs from classic granulocyte precursors. In cancer patients, putative MLPGs were found within the population of CXCR1+CD15−CD14+HLA-DR−/lo monocytic cells. These findings describe a mechanism of abnormal myelopoiesis in cancer and suggest potential new approaches for selective targeting of MDSCs.
Advising Women About Supplemental Screening After Dense Breast Notification
Authors: Ilana B. Richman, Susan H. Busch
Journal: JAMA Internal Medicine (2019)

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 Internal Medicine 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 Internal Medicine journal
Abstract 17111: Defective Activation of Transcription Factor CREB in Circulating CD4+ T-cells Might Explain the Reduced Anti-inflammatory Activity in Patients with Acute Coronary Syndrome
Authors: Davide Flego, Anna Severino, Francesco Trotta, Marco Previtero, Ada F Giglio, Vincenzo A Galiffa, Daniela Pedicino, Luigi M Biasucci, Giovanna Liuzzo, Filippo Crea
Journal: Circulation (2012)

Background. Recent studies have highlighted the importance of T-cell disregulation in acute coronary syndromes (ACS). Cyclic-AMP response element binding protein (CREB) is a crucial transcription f...
Medical cannabis: doctors left to handle “backlash” from patients over lack of availability, MPs say
Authors: Gareth Iacobucci
Journal: BMJ (2019)

The UK government and the drug industry should act urgently to tackle “major gaps” in the evidence base for use of medical cannabis that are restricting availability despite a rescheduling of the drugs last year, a parliamentary inquiry has concluded.

In a report published on Wednesday 3 July the House of Commons Health and Social Care Committee noted that although specialist doctors have been able to prescribe cannabis since November 2018, very few prescriptions have been issued, as most forms of medical cannabis are unlicensed and have not been approved by the National Institute for Health and Care Excellence.1

Poor communication from the …
Abstract 577: Optimization of methods for the analysis of class I MHC peptides by mass spectrometry
Authors: Michael J. Ford, Richard C. Jones, Ravi Amunugama, David Allen, Paul Del Rizzo, James Mobley, Michael Pisano
Journal: Cancer Research (2019)

Abstract Immuno-oncology describes therapeutic approaches exploiting the body's immune system to fight cancer. One approach involves educating the immune-system to recognize and destroy tumor cells by targeting tumor-specific neoantigens. Neoantigens are antigens presented by tumors but not recognized by the immune-system. Identification of Neoantigens is therefore an active area of research and development. The major histocompatibility complex (MHC) plays a crucial role in antigen presentation. Peptides generated by protein degradation in the cytosol are presented, non-covalently bound to MHC Class I molecules, on the surface of cells for inspection by T-lymphocytes. Cytotoxic T lymphocytes (CTL) recognize peptides presented by MHC Class I. The recognition of peptide antigens presented by MHC Class I results in the destruction of the presenting cell by the CTL. Characterization of peptides associated with MHC Class I molecules requires a targeted protein complex enrichment, an unbiased peptide elution and finally a peptide analysis method. Here we present the latest results from our work optimizing and performing a workflow for the analysis of peptides associated with Class I MHC molecules. Citation Format: Michael J. Ford, Richard C. Jones, Ravi Amunugama, David Allen, Paul Del Rizzo, James Mobley, Michael Pisano. Optimization of methods for the analysis of class I MHC peptides by mass spectrometry [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 577.
Metabolite Exchange between Mammalian Organs Quantified in Pigs
Authors: Cholsoon Jang, Sheng Hui, Xianfeng Zeng, Alexis J. Cowan, Lin Wang, Li Chen, Raphael J. Morscher, Jorge Reyes, Christian Frezza, Ho Young Hwang, Akito Imai, Yoshiaki Saito, Keitaro Okamoto, Christine Vaspoli, Loewe Kasprenski, Gerald A. Zsido, Joseph H. Gorman, Robert C. Gorman, Joshua D. Rabinowitz
Journal: Cell Metabolism (2019)
Remodeling the Tumor Microenvironment Sensitizes Breast Tumors to Anti-Programmed Death-Ligand 1 Immunotherapy
Authors: Renee Clift, Jennifer Souratha, Sheryl A. Garrovillo, Susan Zimmerman, Barbara Blouw
Journal: Cancer Research (2019)

Immunotherapies targeting immune checkpoint inhibitors have changed the landscape of cancer treatment, however, many patients are resistant or refractory to immunotherapy. The sensitivity of tumor cells to immunotherapy may be influenced by hyaluronan (HA) accumulation in the tumor microenvironment (TME). Enzymatic degradation of HA by pegvorhyaluronidase alfa (PEGPH20; PVHA) remodels the TME. This leads to reduced tumor interstitial pressure and decompressed tumor blood vessels, which are both associated with increased exposure of tumor cells to chemotherapy drugs. Here, we demonstrate PVHA increased the uptake of anti-programmed death-ligand 1 (PD-L1) antibody in HA-accumulating animal models of breast cancer. The increased levels of anti-PD-L1 antibody were associated with increased accumulation of T cells and natural killer cells and decreased myeloid-derived suppressor cells. PD-L1 blockade significantly inhibited tumor growth when combined with PVHA, but not alone. Our results suggest that PVHA can sensitize HA-accumulating tumors to anti-PD-L1 immunotherapy. SIGNIFICANCE: These findings show removal of hyaluronan in the tumor microenvironment improves immune cells and checkpoint inhibitors access to tumors. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/79/16/4149/F1.large.jpg.
NMD microarray analysis of mutated genes in breast cancer
Authors: Aslaug Aa Muggerud, Maija Wolf, Henrik Edgren, Sami Kilpinen, Therese Sørlie, Olli Kallioniemi
Journal: Cancer Research (2006)

3260  Background and aim: Premature termination codons (PTCs) or nonsense mutations induce rapid transcript degradation in eukaryotic cells through nonsense-mediated mRNA decay (NMD). By pharmacologically blocking the NMD pathway, mutated transcripts containing PTCs are stabilized and accumulate in cells during culture. The corresponding enrichment in mRNA abundance can be monitored by comparing mRNA levels before and after treatment using standard gene expression microarrays. This makes it possible to identify transcripts that are stabilized by the NMD inhibition. The aim of this study is to shed light on putative tumor suppressor genes (TSGs) and splice variants in breast cancer. As bi-allelic inactivation of TSGs often involves deletion of the wild-type allele in addition to the mutated allele, we integrated the NMD microarray data with comparative genomic hybridization (CGH) microarray data. This makes it possible to focus the search of putative mutated TSGs to the deleted chromosomal regions of the cancer cells. Methods: In this study, breast cancer cell lines (MDA-MB-468, MDA-MB-231, MCF-7, ZR-75-1, BT-474 and T47-D) and control cell lines (HMEC, WS1 and IMR90) were treated with emetine, an inhibitor of translation, to pharmacologically block the NMD pathway. Cells were harvested and total RNA were extracted by using RNeasy RNA isolation kit columns (Qiagen, Valencia, CA, USA). Emetine-treated and untreated samples were hybridized to Affymetrix Human Genome U133 Plus 2.0 chips, containing probes for the analysis of over 47.000 transcripts. All chips were normalized using the RMA method implemented in bioconductor package affy. Results: Prolonged half-lives of numerous mRNAs were observed after emetine treatment. Bioinformatic analysis of the data, including data from untreated cells, were used to facilitate distinction of transcripts with truncating mutations from physiologic substrates for NMD (“genomic noise”) as well as transcripts that were otherwise stabilized or induced by the drug. A small set of putative TSGs was identified that are subjected to sequencing. Future plans: Putative mutated genes with specific mRNA enrichment after emetine treatment located in deleted loci of the genome will be sequenced by using conformation-sensitive capillary electrophoresis on the Applied Biosystems 3730 Series Analyzers. Candidate TSGs with confirmed truncating mutations in at least one of the six breast cancer cell lines will be followed up for profiling in clinical samples.
Estimating Implicit and Explicit Gender Bias Among Health Care Professionals and Surgeons
Authors: Arghavan Salles, Michael Awad, Laurel Goldin, Kelsey Krus, Jin Vivian Lee, Maria T. Schwabe, Calvin K. Lai
Journal: JAMA Network Open (2019)

The Implicit Association Test (IAT) is a validated tool used to measure implicit biases, which are mental associations shaped by one's environment that influence interactions with others. Direct evidence of implicit gender biases about women in medicine has yet not been reported, but existing evidence is suggestive of subtle or hidden biases that affect women in medicine.To use data from IATs to assess (1) how health care professionals associate men and women with career and family and (2) how surgeons associate men and women with surgery and family medicine.This data review and cross-sectional study collected data from January 1, 2006, through December 31, 2017, from self-identified health care professionals taking the Gender-Career IAT hosted by Project Implicit to explore bias among self-identified health care professionals. A novel Gender-Specialty IAT was also tested at a national surgical meeting in October 2017. All health care professionals who completed the Gender-Career IAT were eligible for the first analysis. Surgeons of any age, gender, title, and country of origin at the meeting were eligible to participate in the second analysis. Data were analyzed from January 1, 2018, through March 31, 2019.Measure of implicit bias derived from reaction times on the IATs and a measure of explicit bias asked directly to participants.Almost 1 million IAT records from Project Implicit were reviewed, and 131 surgeons (64.9% men; mean [SD] age, 42.3 [11.5] years) were recruited to complete the Gender-Specialty IAT. Healthcare professionals (n = 42 991; 82.0% women; mean [SD] age, 32.7 [11.8] years) held implicit (mean [SD] D score, 0.41 [0.36]; Cohen d = 1.14) and explicit (mean [SD], 1.43 [1.85]; Cohen d = 0.77) biases associating men with career and women with family. Similarly, surgeons implicitly (mean [SD] D score, 0.28 [0.37]; Cohen d = 0.76) and explicitly (men: mean [SD], 1.27 [0.39]; Cohen d = 0.93; women: mean [SD], 0.73 [0.35]; Cohen d = 0.53) associated men with surgery and women with family medicine. There was broad evidence of consensus across social groups in implicit and explicit biases with one exception. Women in healthcare (mean [SD], 1.43 [1.86]; Cohen d = 0.77) and surgery (mean [SD], 0.73 [0.35]; Cohen d = 0.53) were less likely than men to explicitly associate men with career (B coefficient, -0.10; 95% CI, -0.15 to -0.04; P < .001) and surgery (B coefficient, -0.67; 95% CI, -1.21 to -0.13; P = .001) and women with family and family medicine.The main contribution of this work is an estimate of the extent of implicit gender bias within surgery. On both the Gender-Career IAT and the novel Gender-Specialty IAT, respondents had a tendency to associate men with career and surgery and women with family and family medicine. Awareness of the existence of implicit biases is an important first step toward minimizing their potential effect.
Epidemiology of post-influenza bacterial pneumonia due to Panton–Valentine leucocidin positive Staphylococcus aureus in intensive care units: a retrospective nationwide study
Authors: Audrey Jacquot, Charles-Edouard Luyt, Antoine Kimmoun, Bruno Levy, Elisabeth Baux, Charles Vidal, Sami Hraiech, Jean-Pierre Quenot, Lara Zafrani, Francis Schneider, Pierre Kalfon, Vincent Piriou, Saadalla Nseir, Paul Jaubert, Jonathan Messika, Muriel Fartoukh, Xavier Valette, Alexandre Lautrette, Antoine Marchalot, Nicolas Terzi, Guillaume Schnell, Charlène Le Moal, Emmanuel Novy, Jérémie Lemarié, Arnaud Galbois, Jean-Marc Tadié, Gabriel Preda, Raphaël Clere-Jehl, François Vandenesch, Eliane Albuisson, Corentine Alauzet, Bruno Hoen, Evelyne Schvoerer, Isabelle Clerc-Urmès, Céline Pulcini
Journal: Intensive Care Medicine (2019)
Accuracy of the 2017 international recommendations for clinicians who interpret adolescent athletes’ ECGs: a cohort study of 11 168 British white and black soccer players
Authors: Aneil Malhotra, Harshil Dhutia, Tee-Joo Yeo, Gherardo Finocchiaro, Sabiha Gati, Paulo Bulleros, Zephyr Fanton, Efstathios Papatheodorou, Chris Miles, Tracey Keteepe-Arachi, Joyee Basu, Gemma Parry-Williams, Keerthi Prakash, Belinda Gray, Andrew D'Silva, Bode Ensam, Elijah Behr, Maite Tome, Michael Papadakis, Sanjay Sharma
Journal: British Journal of Sports Medicine (2019)

Aim To investigate the accuracy of the recently published international recommendations for ECG interpretation in young athletes in a large cohort of white and black adolescent soccer players. Methods 11 168 soccer players (mean age 16.4±1.2 years) were evaluated with a health questionnaire, ECG and echocardiogram; 10 581 (95%) of the players were male and 10 163 (91%) were white. ECGs were retrospectively analysed according to (1) the 2010 European Society of Cardiology (ESC) recommendations, (2) Seattle criteria, (3) refined criteria and (4) the international recommendations for ECG interpretation in young athletes. Results The ESC recommendations resulted in a higher number of abnormal ECGs compared with the Seattle, refined and international criteria (13.2%, 4.3%, 2.9% and 1.8%, respectively). All four criteria were associated with a higher prevalence of abnormal ECGs in black athletes compared with white athletes (ESC: 16.2% vs 12.9%; Seattle: 5.9% vs 4.2%; refined: 3.8% vs 2.8%; international 3.6% vs 1.6%; p&lt;0.001 each). Compared with ESC recommendations, the Seattle, refined and international criteria identified a lower number of abnormal ECGs—by 67%, 78% and 86%, respectively. All four criteria identified 36 (86%) of 42 athletes with serious cardiac pathology. Compared with ESC recommendations, the Seattle criteria improved specificity from 87% to 96% in white athletes and 84% to 94% in black athletes. The international recommendations demonstrated the highest specificity for white (99%) and black (97%) athletes and a sensitivity of 86%. Conclusions The 2017 international recommendations for ECG interpretation in young athletes can be applied to adolescent athletes to detect serious cardiac disease. These recommendations perform more effectively than previous ECG criteria in both white and black adolescent soccer players.