tbuckley/cabot-search huggingface dataset:
Abstract B19: Targeting ATM to sensitize pancreatic cancer to immunotherapy and radiotherapy
Authors: Michael Green, Qiang Zhang, Xueting Lang, Yu Lei, Theodore S. Lawrence, Weiping Zou, Meredith A. Morgan
Journal: Cancer Research (2019)

Abstract Combinatorial strategies are needed to overcome the resistance of pancreatic cancer to immune checkpoint blockade (ICB). DNA damage activates the innate immune response and improves ICB efficacy. We have studied the role of ATM, a core component of the DNA damage response, on pancreatic tumor immunogenicity in vitro and in vivo. Inhibition of ATM increased tumoral interferon signaling in a cGAS/STING-independent but TBK1 and SRC-dependent manner. The combination of ATM inhibition with radiation enhanced TBK1 activity, T1IFN production, and antigen presentation in vitro. Furthermore, ATM silencing enhanced T-cell trafficking in vivo and increased the sensitivity of pancreatic tumors to PD-L1 blocking antibody. The potential of ATM as a target for combinatorial strategy with ICB and radiation in pancreatic cancer will be discussed. Citation Format: Michael Green, Qiang Zhang, Xueting Lang, Yu Lei, Theodore S. Lawrence, Weiping Zou, Meredith A. Morgan. Targeting ATM to sensitize pancreatic cancer to immunotherapy and radiotherapy [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr B19.
SHP1 regulates a STAT6–ITGB3 axis in FLT3ITD-positive AML cells
Authors: Daniela Reich, Anne Kresinsky, Jörg P. Müller, Reinhard Bauer, Julia Kallenbach, Tina M. Schnoeder, Florian H. Heidel, Reinhard Fässler, Matthias Mann, Frank-D. Böhmer, Ashok Kumar Jayavelu
Journal: Leukemia (2019)
Age-dependent manifestations and case definitions of paediatric Zika: a prospective cohort study
Authors: Raquel Burger-Calderon, Fausto Bustos Carrillo, Lionel Gresh, Sergio Ojeda, Nery Sanchez, Miguel Plazaola, Leah Katzelnick, Brenda Lopez Mercado, Jairo Carey Monterrey, Douglas Elizondo, Sonia Arguello, Andrea Nuñez, Aubree Gordon, Angel Balmaseda, Guillermina Kuan, Eva Harris
Journal: The Lancet Infectious Diseases (2019)
CRMP5-IgG–Associated Paraneoplastic Myelopathy With PD-L1 Inhibitor Therapy
Authors: Amy Kunchok, Anastasia Zekeridou, Sean Pittock
Journal: JAMA Neurology (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 Neurology 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 Neurology journal
B Cell Specific Knockdown of the Erythropoietin (EPO) Receptor Attenuates EPO-Induced Bone Loss in Mice
Authors: Albert Kolomansky, Naamit Deshet-Unger, Nathalie Ben-Califa, Zamzam Awida, Maria Ibrahim, Tamar Liron, Sahar Hiram-Bab, Howard S. Oster, Moshe Mittelman, Martina Rauner, Ben Wielockx, Yankel Gabet, Drorit Neumann
Journal: Blood (2019)
Vasodilator Therapy in Acute Heart Failure
Authors: Gregory Curfman
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
MRP3‐Mediated Chemoresistance in Cholangiocarcinoma: Target for Chemosensitization Through Restoring SOX17 Expression
Authors: Elisa Lozano, Maitane Asensio, Laura Perez‐Silva, Jesus M. Banales, Oscar Briz, Jose J.G. Marin
Journal: Hepatology (2019)

Background and Aims A limitation for the treatment of unresectable cholangiocarcinoma (CCA) is its poor response to chemotherapy, which is partly due to reduction of intracellular levels of anticancer drugs through ATP‐binding cassette (ABC) pumps. Low expression of SOX17 (SRY‐box containing gene 17), a transcription factor that promotes biliary differentiation and phenotype maintenance, has been associated with cholangiocyte malignant transformation. Whether SOX17 is also involved in CCA chemoresistance is investigated in this study. Approach and Results SOX17 expression in human CCA cells (EGI‐1 and TFK‐1) selectively potentiated cytotoxicity of SN‐38, 5‐fluorouracil and mitoxantrone, but not that of gemcitabine, capecitabine, cisplatin, or oxaliplatin. The analysis of the resistome by TaqMan low‐density arrays revealed changes affecting primarily ABC pump expression. Single‐gene quantitative real‐time PCR, immunoblot, and immunofluorescence analyses confirmed that MRP3 (multidrug resistance associated protein 3), which was highly expressed in CCA human tumors, was down‐regulated in SOX17‐transduced CCA cells. The substrate specificity of this pump matched that of SOX17‐induced in vitro selective chemosensitization. Functional studies showed lower ability of SOX17‐expressing CCA cells to extrude specific MRP3 substrates. Reporter assay of MRP3 promoter ( ABCC3pr ) revealed that ABCC3pr activity was inhibited by SOX17 expression and SOX2/SOX9 silencing. The latter was highly expressed in CCA. Moreover, SOX2/9, but not SOX17, induced altered electrophoretic mobility of ABCC3pr , which was prevented by SOX17. The growth of CCA tumors subcutaneously implanted into immunodeficient mice was inhibited by 5‐fluorouracil. This effect was enhanced by co‐treatment with adenoviral vectors encoding SOX17. Conclusions SOX9/2/17 are involved in MRP3‐mediated CCA chemoresistance. Restored SOX17 expression, in addition to its tumor suppression effect, induces selective chemosensitization due to MRP3 down‐regulation and subsequent intracellular drug accumulation.
Two-Year Clinical Trial of the Low-Concentration Atropine for Myopia Progression (LAMP) Study
Authors: Jason C. Yam, Fen Fen Li, Xiujuan Zhang, Shu Min Tang, Benjamin H.K. Yip, Ka Wai Kam, Simon T. Ko, Alvin L. Young, Clement C. Tham, Li Jia Chen, Chi Pui Pang
Journal: Ophthalmology (2019)
Suboptimal endoscopic cancer recognition in colorectal lesions in a national bowel screening programme
Authors: Jasper L A Vleugels, Lianne Koens, Marcel G W Dijkgraaf, Britt Houwen, Yark Hazewinkel, Paul Fockens, Evelien Dekker
Journal: Gut (2019)

The worldwide implementation of bowel cancer screening programmes (BCSPs) results in a growing number of early T1 colorectal cancers (T1 CRCs). Successful treatment of T1 CRCs starts with accurately recognising these lesions during endoscopy. This study performed in the Dutch BCSP showed that endoscopists correctly diagnosed T1 CRCs in only 39% of 92 cases (95% CI 30 to 49) and that this limited diagnostic accuracy of optical diagnosis resulted in different treatment outcomes. In patients with T1 CRCs that were optically not diagnosed as cancer and treated locally, adjuvant surgery was performed in 41% of cases, compared with 11% of patients with T1 CRCs that were correctly optically diagnosed (p=0.02).

In this prospective multicentre study (trial registration number: NTR4635, NCT02407925), endoscopists accredited for fecal immunochemical test (FIT)-positive colonoscopies within the Dutch BCSP were trained in optical diagnosis with our validated National Institute for Health and Care Excellence (NICE)-WASP (Workgroup serrAted polypS and Polyposis) module (online supplementary material 1 for full methods).1 2 A total of 27 endoscopists completed the training successfully and entered the prospective study, in which the endoscopists as well as pathologists reported their findings in a predefined structure. This facilitated high-quality data collection and ensured collection of exact data on all aspects of each detected lesion as location, size, Paris morphology, optical diagnosis (colorectal cancer (CRC), adenoma, hyperplastic polyp, sessile serrated lesion or other), endoscopic treatment method (biopsy, cold or hot snare polypectomy, endoscopic mucosal resection, biopsy for diagnosis or no treatment), completeness of resection and whether a tattoo was placed. Participating endoscopists recorded optical diagnosis using narrow band imaging in all consecutive FIT-positive colonoscopies for the Dutch BCSP during 1 year. Local treatment was defined as endoscopic resection or transanal endoscopic microsurgery. For all patients initially diagnosed with T1 CRCs, the original H&E staining slides were collected …
UK is failing on UN pledge to “leave no one behind” on healthcare, report finds
Authors: Elisabeth Mahase
Journal: BMJ (2019)

Many countries in the European Union, including the UK, are failing to uphold their pledge to “leave no one behind” in regard to health, says a report from Doctors of the World.1

The pledge to provide universal health coverage (UHC) was set out by the United Nations in 2015 as part of the 2030 agenda for sustainable development, which also called for action to end poverty and protect the planet.2 But the medical charity found that many countries were not living up to their pledge and that vulnerable people …
Abstract 02: Effect of Airway Insertion First-Pass Success Upon Patient Outcomes in the Pragmatic Airway Resuscitation Trial
Authors: Jason Lesnick, Yefei Zhang, Justin X Moore, Mohamud R Daya, Jeffrey W Jarvis, Graham Nichol, Jestin N Carlson, Cameron D Klug, Robert Schmicker, David Dennis, Ahamed H Idris, George Sopko, Pratik Doshi, Eric Madden, Henry E Wang
Journal: Circulation (2019)

Introduction: The multicenter Pragmatic Airway Resuscitation Trial (PART) demonstrated better adult out-of-hospital cardiac arrest (OHCA) outcomes with initial laryngeal tube (LT) insertion than endotracheal intubation (ETI) airway management. While emphasized in clinical practice, the effect of advanced airway insertion first-pass success (FPS) upon outcomes after OHCA is unknown. We sought to determine the direct and indirect mediating effects of LT and ETI FPS upon adult OHCA in a secondary analysis of PART. HYPOTHESES: 1) FPS associated with adult OHCA outcomes. 2) FPS mediates (explains) the association between airway type (LT vs. ETI) and adult OHCA outcomes. Methods: We defined FPS as successful LT insertion or ETI on the first attempt as reported by EMS personnel. We examined the outcomes return of spontaneous circulation (ROSC), 72-hour survival, hospital survival, and hospital survival with favorable neurologic function (MRS ≤3). Using multivariable GEE, we determined the association between FPS and outcomes after OHCA, adjusting for age, sex, witnessed arrest status, bystander CPR, initial rhythm, and trial randomization. Using the method of Baron and Kenny, we used mediation analysis to explain the contribution of FPS towards differences in OHCA outcomes between LT and ETI. Results: Of 3,004 patients enrolled in the trial, 1,423 received LT, 1,227 received ETI, 354 received bag-valve-mask ventilation only. FPS was: LT 90.3% and ETI 51.5%. FPS was associated with increased ROSC (adjusted OR 1.36, 95% CI 1.04-1.78) and 72h survival (1.45; 1.20-1.74) but not hospital survival (0.94; 0.67-1.31) or hospital survival with favorable neurologic function (0.70; 0.40-1.23). FPS had a strong mediating effect on the OHCA outcome differences between LT and ETI; 72h survival (74% mediated); ROSC (53% mediated); hospital survival (52% mediated); hospital survival with favorable neurologic status (35% mediated). Conclusion: In adult with OHCA, airway insertion FPS is associated with increased ROSC and 72h survival. Differences in OHCA outcomes between LT and ETI are largely explained by differences in FPS. EMS personnel should emphasize FPS in the advanced airway management of OHCA.
Associations between national development indicators and the age profile of people who inject drugs: results from a global systematic review and meta-analysis
Authors: Lindsey A Hines, Adam Trickey, Janni Leung, Sarah Larney, Amy Peacock, Louisa Degenhardt, Samantha Colledge, Matthew Hickman, Jason Grebely, Evan B Cunningham, Jack Stone, Kostyantyn Dumchev, Paul Griffiths, Peter Vickerman, Richard P Mattick, Michael Lynskey
Journal: The Lancet Global Health (2019)

Globally, an estimated 15·6 million people inject drugs. We aimed to investigate global variation in the age profile of people who inject drugs (PWID), identify country-level factors associated with age of PWID, and assess the association between injecting drug use (IDU) in young people and rates of injecting and sexual risk behaviours at the country level.
From temporal updating to temporal reasoning: Developments in young children's temporal representations
Authors: Estelle M. Y. Mayhew, Meng Zhang, Judith A. Hudson
Journal: Behavioral and Brain Sciences (2019)

Abstract Evidence from our research on young children's temporal understanding supports Hoerl &amp; McCormack's view that young children rely on a temporal updating system to change representations over time. We propose that the shift from temporal updating to temporal reasoning is enabled by children's expanding representations of event sequences, along with developments in language, memory, and other cognitive competencies.
Selection of lung cancer-associated scFv antibodies from cultured cells
Authors: P. P. Massion, T. V. Pedchenko, D. V. Parekh, R. Mernaugh
Journal: Journal of Clinical Oncology (2009)

e22137 Background: Lung cancer is the most common cause of cancer-related deaths in the world. There is a critical need for new strategies of early lung cancer detection. The identification of tumor-associated antigens and corresponding antibodies is one approach to discovery of diagnostic biomarkers. We used a large phage-displayed recombinant antibody library and normal human lung epithelial and non-small cell lung cancer cell lines to select for and identify recombinant antibodies specific for proteins expressed, or over-expressed, in lung cancer. Methods: The antibody library was used to select for recombinant scFv antibodies reactive with proteins present, or aberrantly expressed, in non-small cell lung cancer cell lines (A549, H549, H157, H23) in comparison to normal lung cell lines (BEAS-2B, 16-HBE, KT). Soluble scFv antibodies were obtained through 2 rounds of phage antibody cross-absorption (on normal cell lines) and selection (on non-small lung cancer cell lines). Soluble scFv were assayed by a high-throughput fluorometric microvolume assay technology (FMAT) against normal and cancer lung cell line proteins. ScFv antibodies selected by FMAT were evaluated further with Western blot-based assays. Results: More than 100 scFv antibodies identified by FMAT bound preferentially to proteins in lung cancer. Of these, 46 scFv were assayed by a high throughput Western slot blot immunoassay against pooled normal lung and lung cancer cell lysates. Eight scFv were assayed in Western blot against individual lung normal and non-small lung cancer cell line lysates. Four of these demonstrated differential binding to normal and cancer cell lysates. Conclusions: In summary, we were able to detect cancer-associated antigens in lung cancer cell lines using a phage display antibody library. In combination with high-throughput fluorescent and Western blot assays, four unique scFv antibodies were selected that differentially bound to normal and lung cancer cell lysates. These scFv will be tested as candidate biomarkers of lung cancer in independent tissue and serum samples from patient with and without lung cancer to determine utility for use in lung cancer diagnosis. No significant financial relationships to disclose.
Remote Ischemic Pre-Conditioning Attenuates Adverse Cardiac Remodeling and Mortality Following Doxorubicin Administration in Mice
Authors: Zachary M. Gertz, Chad Cain, Donatas Kraskauskas, Teja Devarakonda, Adolfo G. Mauro, Jeremy Thompson, Arun Samidurai, Qun Chen, Sarah W. Gordon, Edward J. Lesnefsky, Anindita Das, Fadi N. Salloum
Journal: JACC CardioOncology (2019)

Because of its multifaceted cardioprotective effects, remote ischemic pre-conditioning (RIPC) was examined as a strategy to attenuate doxorubicin (DOX) cardiotoxicity. The use of DOX is limited by dose-dependent cardiotoxicity and heart failure. Oxidative stress, mitochondrial dysfunction, inflammation, and autophagy modulation have been proposed as mediators of DOX cardiotoxicity. After baseline echocardiography, adult male CD1 mice were randomized to either sham or RIPC protocol (3 cycles of 5 min femoral artery occlusion followed by 5 min reperfusion) 1 h before receiving DOX (20 mg/kg, intraperitoneal). The mice were observed primarily for survival over 85 days (86 mice). An additional cohort of 50 mice was randomized to either sham or RIPC 1 h before DOX treatment and was followed for 25 days, at which time cardiac fibrosis, apoptosis, and mitochondrial oxidative phosphorylation were assessed, as well as the expression profiles of apoptosis and autophagy markers. Survival was significantly improved in the RIPC cohort compared with the sham cohort (p = 0.007). DOX-induced cardiac fibrosis and apoptosis were significantly attenuated with RIPC compared with sham (p < 0.05 and p < 0.001, respectively). Although no mitochondrial dysfunction was detected at 25 days, there was a significant increase in autophagy markers with DOX that was attenuated with RIPC. Moreover, DOX caused a 49% decline in cardiac BCL2/BAX expression, which was restored with RIPC (p < 0.05 vs. DOX). DOX also resulted in a 17% reduction in left ventricular mass at 25 days, which was prevented with RIPC (p < 0.01), despite the lack of significant changes in left ventricular ejection fraction. Our preclinical results suggested that RIPC before DOX administration might be a promising approach for attenuating DOX cardiotoxicity.
A Variant of SLC1A5 Is a Mitochondrial Glutamine Transporter for Metabolic Reprogramming in Cancer Cells
Authors: Hee Chan Yoo, Seung Joon Park, Miso Nam, Juwon Kang, Kibum Kim, Joo Hye Yeo, Joon-Ki Kim, Yunkyung Heo, Hee Seung Lee, Myeong Youl Lee, Chang Woo Lee, Jong Soon Kang, Yun-Hee Kim, Jinu Lee, Junjeong Choi, Geum-Sook Hwang, Seungmin Bang, Jung Min Han
Journal: Cell Metabolism (2019)
Inhaled amikacin adjunctive to intravenous standard-of-care antibiotics in mechanically ventilated patients with Gram-negative pneumonia (INHALE): a double-blind, randomised, placebo-controlled, phase 3, superiority trial
Authors: Michael S Niederman, Jeff Alder, Matteo Bassetti, Francis Boateng, Bin Cao, Kevin Corkery, Rajiv Dhand, Keith S Kaye, Robert Lawatscheck, Patrick McLeroth, David P Nicolau, Chen Wang, G Christopher Wood, Richard G Wunderink, Jean Chastre
Journal: The Lancet Infectious Diseases (2019)
Potentiation of cetuximab by inhibition of Tregs in metastatic squamous cell cancers of head and neck.
Authors: Gautam Gopalji Jha, Jeffrey S Miller
Journal: Journal of Clinical Oncology (2013)

TPS6101 Background: There are few effective treatment options for patients with metastatic squamous cell cancers of head and neck (HNSCC). The only significant advance in the last few decades has been approval of cetuximab, a monoclonal antibody directed against the overexpressed epidermal growth factor receptor (EGFR). Despite its high specificity for EGFR, cetuximab as single-agent has resulted in response rates of only 13% and PFS of less than 2 months. Recent evidence suggests that cetuximab may induce tumor cell killing through an immune-mediated ADCC and not through blockade of EGFR signaling. Cetuximab binds EGFR on tumor cells making them targets for natural killer (NK) cell-mediated lysis. The effectiveness of cetuximab is limited by the tumor mediated immune-suppression that inhibits NK and other effector cells. This local and possibly generalized immune suppression is primarily mediated by regulatory T cells (Tregs) which inhibit NK cells and other effector cells. HNSCC tumors are highly immunosuppressive and characterized by marked and persistent elevation of inhibitory Tregs. The myelosuppression and immunosuppression caused by cyclophosphamide is dose dependent, and at lower doses cyclophosphamide has been shown to selectively deplete Tregs, restore NK cell activity and paradoxically induce auto-immunity. Objectives: To assess potentiation of clinical response by tracking PFS, OS and HRQOL and immune augmentation in tumor biopsies and blood samples. Methods: The current pilot study (n=15) will assess the hypothesis that Tregs, which are elevated in HNSCC, can be suppressed with cyclophosphamide and that this suppression can lead to improved anti-tumor responses mediated by cetuximab. Eligibility: Metastatic HNSCC progressed on initial chemotherapy or not a candidate for platinum Treatment: Daily oral cyclophosphamide 50 mg bid and weekly cetuximab (SOC). Patients will have blood collected for immune monitoring at weeks 0, 3, 6, 12 and pre and post treatment biopsies at week 0, 6. T cell subsets, NK cell function, Tregs, MDSC will be assessed at tumor site and in blood for immune response. Restaging CT scans will be done pretreatment and at weeks 6, 12. Clinical trial information: NCT01581970.
Abstract MP36: APOL1 and Risk of Incident Stroke in African Americans: The Atherosclerosis Risk in Communities Study
Authors: Meredith C Foster, Josef Coresh, Myriam Fornage, Eric Boerwinkle, Aaron R Folsom, A R Sharrett, Elizabeth Selvin, Thomas Mosley, Ching-Yu Cheng, Rulan Parekh, W. H. Linda Kao
Journal: Circulation (2013)

Background: African Americans (AAs) have an increased stroke burden when compared to European Americans (EAs) even after accounting for age, sex, and socioeconomic status. Genetic factors may contr...