tbuckley/cabot-search huggingface dataset:
A virus-like particle vaccine prevents equine encephalitis virus infection in nonhuman primates
Authors: Sung-Youl Ko, Wataru Akahata, Eun Sung Yang, Wing-Pui Kong, Crystal W. Burke, Shelley P. Honnold, Donald K. Nichols, Yan-Jang S. Huang, Gretchen L. Schieber, Kevin Carlton, Luis DaSilva, Vicki Traina-Dorge, Dana L. Vanlandingham, Yaroslav Tsybovsky, Tyler Stephens, Ulrich Baxa, Stephen Higgs, Chad J. Roy, Pamela J. Glass, John R. Mascola, Gary J. Nabel, Srinivas S. Rao
Journal: Science Translational Medicine (2019)

Western, Eastern, and Venezuelan equine encephalitis viruses (WEEV, EEEV, and VEEV, respectively) are important mosquito-borne agents that pose public health and bioterrorism threats. Despite considerable advances in understanding alphavirus replication, there are currently no available effective vaccines or antiviral treatments against these highly lethal pathogens. To develop a potential countermeasure for viral encephalitis, we generated a trivalent, or three-component, EEV vaccine composed of virus-like particles (VLPs). Monovalent VLPs elicited neutralizing antibody responses and protected mice and nonhuman primates (NHPs) against homologous challenges, but they were not cross-protective. In contrast, NHPs immunized with trivalent VLPs were completely protected against aerosol challenge by each of these three EEVs. Passive transfer of IgG from immunized NHPs protected mice against aerosolized EEV challenge, demonstrating that the mechanism of protection was humoral. Because they are replication incompetent, these trivalent VLPs represent a potentially safe and effective vaccine that can protect against diverse encephalitis viruses.
Medical Therapy for Heart Failure Associated With Pulmonary Hypertension
Authors: Jason G.E. Zelt, Ketul R. Chaudhary, Virgilio J. Cadete, Lisa M. Mielniczuk, Duncan J. Stewart
Journal: Circulation Research (2019)

The past 2 decades have witnessed a >40% improvement in mortality for patients with heart failure and left ventricular systolic dysfunction. 1 This success has coincided with the stepwise availability of drugs that target neurohormonal activation: β-adrenergic receptor blockers (β-blockers), ACE (angiotensin-converting enzyme) inhibitors and ANG (angiotensin) II blockers, neprilysin inhibitors, and aldosterone antagonists. Our understanding of right heart failure (RHF) has lagged behind and many proven targeted therapies for left heart failure do not appear to provide similar benefits for RHF. Until recently, the right ventricle (RV) has often been viewed as less important than the left ventricle and in contemporary literature received the moniker "The Forgotten Ventricle". Recent advances in echocardiography and magnetic resonance imaging have enabled detailed assessments of RV anatomy and physiology in both health and disease allowing us to more accurately describe the clinical sequelae and end-organ manifestations of RHF. RV function is now recognized as one of the most important predictors of prognosis in many cardiovascular disease states. 2 Despite the significance of RV function to survival, there are no clinically approved therapies that directly nor selectively improve RV function. As well, relative to our understanding of left heart failure, the basis for RHF remains poorly understood. This article aims to condense the current knowledge on RV adaptation and failure, review current management strategies for RHF, and explore evolving therapeutic approaches.
Exposing drug industry funding of UK patient organisations
Authors: Piotr Ozieranski, Emily Rickard, Shai Mulinari,
Journal: BMJ (2019)

From 2012 to 2016 the drug industry donated over £57m (€65m; $73m) to UK patient organisations, with the annual sum more than doubling over the periodThe funding benefited a small number of organisations and activities related to research and public involvementThe industry gave priority to commercially high profile conditions
FRI0095 Cognitive impairment related to systemic lupus erythematosus
Authors: S Appenzeller, LT Costallat
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is a disease with a broad spectrum of clinical manifestations and a typical course of remission and exacerbation. Various neuropsychiatric manifestations have been considered to be important features of SLE and indicative of Central Nervous System (CNS) involvement, including cognitive impairment, anxiety and depression. <h3>Objectives</h3> To determine the point prevalence of cognitive impairment in patients with SLE. To investigate associations between cognitive impairment and psychiatric disorders, corticosteroid therapy, systemic disease activity and central nervous system (CNS) involvement. <h3>Methods</h3> A cross-sectional study of 40 patients with SLE was analysed. To assess cognitive impairment, anxiety and depression standardised psychiatric and clinical research methods were used (Minimental, logic memory tests, short and long memory tests, verbal fluency test, attention tests, BPRS, HAD CAGE and BECK's inventory for measuring depression). Systemic disease activity was measured by SLEDAI. Statistics were performed by chi-square test and by Fisher's exact test. <h3>Results</h3> Cognitive impairment was observed in 75% in SLE. There was no significant relation to the duration of the illness, use of corticotherapy or systemic disease activity. There was a significant association between cognitive impairment and anxiety (p &lt; 0.05) in SLE patients. The same was not observed with depression. CNS involvement was observed in 70% in SLE. Anxiety was observed in 40% of CNS-SLE (p &lt; 0.05). Cognitive impairment was present in 53.6% of CNS-SLE and in 66.6% of non CNS-SLE. <h3>Conclusion</h3> The high prevalence of cognitive disorders in our study group could be related to the high prevalence of anxiety, rather than direct involvement of the CNS by SLE. Marked cognitive impairment was present in a significant percentage of patients without CNS involvement. Supported by FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo). <h3>References</h3> Bluestein HG. The central nervous system in lupus erythematosus. In: Lahita RG, ed. <i>Systemic lupus erythematosus</i>. New york: Crurchill Livingstone, 1992: 639–55 West SG. Neuropsychiatric lupus. Rheum Dis Clin North Am. 1994;20:129–58 Bruyin GAW. Controversies in lupus: nervous system involvement. Ann Rheum Dis. 1995;54:159–67 Calabrese LV, Stern TA. Neuropsychiatric manifestations of systemic lupus erythematosus. Psychossomatics 1995;36:344–59 Wallace DJ, Metzger AL. Systemic lupus erythematosus and the nervous system. In: Wallace DJ, Hanh BH, eds. <i>Dubois lupus erythematosus</i>. Philadelphia: Lea &amp; Febiger, 1993: 370–85 Denburg SD, Carbotte RM, Denburg JÁ. Psychological aspects of systemic lupus erythematosus: cognitive function, mood and self-report. J Rheumatol. 1997;24:998–1003
Aged blood impairs hippocampal neural precursor activity and activates microglia via brain endothelial cell VCAM1
Authors: Hanadie Yousef, Cathrin J. Czupalla, Davis Lee, Michelle B. Chen, Ashley N. Burke, Kristy A. Zera, Judith Zandstra, Elisabeth Berber, Benoit Lehallier, Vidhu Mathur, Ramesh V. Nair, Liana N. Bonanno, Andrew C. Yang, Todd Peterson, Husein Hadeiba, Taylor Merkel, Jakob Körbelin, Markus Schwaninger, Marion S. Buckwalter, Stephen R. Quake, Eugene C. Butcher, Tony Wyss-Coray
Journal: Nature Medicine (2019)
EUCAST disc diffusion criteria for the detection of mecA-Mediated β-lactam resistance in Staphylococcus pseudintermedius: oxacillin versus cefoxitin
Authors: R. Skov, A. Varga, E. Matuschek, J. Åhman, D. Bemis, B. Bengtsson, M. Sunde, R. Humphries, L. Westblade, L. Guardabassi, G. Kahlmeter
Journal: Clinical Microbiology and Infection (2019)
Single and Dual Targeting of Mutant EGFR with an Allosteric Inhibitor
Authors: Ciric To, Jaebong Jang, Ting Chen, Eunyoung Park, Mierzhati Mushajiang, Dries J.H. De Clercq, Man Xu, Stephen Wang, Michael D. Cameron, David E. Heppner, Bo Hee Shin, Thomas W. Gero, Annan Yang, Suzanne E. Dahlberg, Kwok-Kin Wong, Michael J. Eck, Nathanael S. Gray, Pasi A. Jänne
Journal: Cancer Discovery (2019)

Allosteric kinase inhibitors offer a potentially complementary therapeutic strategy to ATP-competitive kinase inhibitors due to their distinct sites of target binding. In this study, we identify and study a mutant-selective EGFR allosteric inhibitor, JBJ-04-125-02, which as a single agent can inhibit cell proliferation and EGFRL858R/T790M/C797S signaling in vitro and in vivo. However, increased EGFR dimer formation limits treatment efficacy and leads to drug resistance. Remarkably, osimertinib, an ATP-competitive covalent EGFR inhibitor, uniquely and significantly enhances the binding of JBJ-04-125-02 for mutant EGFR. The combination of osimertinib and JBJ-04-125-02 results in an increase in apoptosis, a more effective inhibition of cellular growth, and an increased efficacy in vitro and in vivo compared with either single agent alone. Collectively, our findings suggest that the combination of a covalent mutant-selective ATP-competitive inhibitor and an allosteric EGFR inhibitor may be an effective therapeutic approach for patients with EGFR-mutant lung cancer. SIGNIFICANCE: The clinical efficacy of EGFR tyrosine kinase inhibitors (TKI) in EGFR-mutant lung cancer is limited by acquired drug resistance, thus highlighting the need for alternative strategies to inhibit EGFR. Here, we identify a mutant EGFR allosteric inhibitor that is effective as a single agent and in combination with the EGFR TKI osimertinib.This article is highlighted in the In This Issue feature, p. 813.
Abstract 3617: A paradigm shift for insulin-like growth factor 1 receptor function in triple negative breast cancers
Authors: Alison Obr, Sushil Kumar, Raymond Birge, Teresa Wood
Journal: Cancer Research (2017)

Abstract Signaling through the insulin-like growth factor type 1 receptor (IGF-1R) is complex in breast cancers. Early studies reported that expression of the IGF-1R correlated with estrogen receptor (ER) expression and predicted a favorable phenotype. Moreover, loss of IGF-1R has been associated with breast tumor progression into a more undifferentiated phenotype. We have generated and characterized a mouse line containing both MMTV-Wnt1 and MMTV-dnIGF-1R (kinase dead-IGF-1R) transgenes (referred to subsequently as bigenic mice) that leads to increased mammary tumor initiation and metastasis. These data support the hypothesis that the IGF-1R functions in suppressing metastasis in certain contexts and subtypes of triple negative breast cancers (TNBCs). Recent analyses of TCGA human datasets support the relevance of our model in human TNBCs that have reduced IGF-1R expression and increased expression of Wnt1 and the Frizzled co-receptor Lrp6. We have identified alterations in a number of target genes that potentially regulate metastasis in the bigenic primary tumors including increases in interleukin-6 (IL-6), Slug, Vimentin, Zeb 1/2 and decreases in E-cadherin expression as assessed by Qiagen specific qPCR and single gene qPCR. Furthermore, a subset of anti-inflammatory chemokines and cytokines were assessed by a targeted qPCR array revealing increases in interleukin-4, interleukin-10, and C-C motif chemokine ligand-2 and decreases in tumor necrosis factor-alpha in the bigenic tumors indicating a tumor associated macrophage phenotype. By flow cytometry analysis, the ratio of CD4+ T cells to CD8+ T cells is increased in the bigenic tumors suggesting a tumor promoting immune microenvironment. However, increased expression of IL-6 in the bigenic tumors is specific to the luminal tumor cells, and inhibition of IGF-1R in the MCF7 human breast cancer cell line results in increases in IL-6, Slug, and Zeb 1/2 expression suggesting the tumor cells activate EMT and a pro-tumorigenic microenvironment in response to decreased IGF-1R. Moreover, inhibition of IGF-1R in human breast cancer cells and MMTV-Wnt1 mouse tumor cells results in increased cell motility and invasion as assessed by the xCELLigence motility assay. Taken together, our data support the hypothesis that IGF-1R acts as a negative regulator of mediators that promote migration, invasion, and metastasis in TNBCs. Citation Format: Alison Obr, Sushil Kumar, Raymond Birge, Teresa Wood. A paradigm shift for insulin-like growth factor 1 receptor function in triple negative breast cancers [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 3617. doi:10.1158/1538-7445.AM2017-3617
Breast cancer specific graded prognostic assessment (BC-GPA) score and outcome of HER 2 positive breast cancer patients with brain metastases: A single centre retrospective analysis
Authors: S. Kate, N. Paleja, R. Patil, S. Bhalerao, S. Dhande, V. Palve, M. Targe, R. Nagarkar, L. Fernandes
Journal: Annals of Oncology (2019)

Background: Her2 overexpressing breast cancer patients are at a high risk for developing brain metastases. We analysed the group of Her 2 overexpressing patients and studied disease and treatment related characteristics of those with and without brain metastases. Methods: We retrospectively analysed 102 Her 2 overexpressing breast cancer patients who received treatment in our centre from 2013 to 2017, out of which 20 patients (19.6%) were found to have brain metastases. Descriptive data was accumulated from electronic medical records. Survival plot was calculated from Kaplan Meir and compared between groups using Log Rank test. Results: The median age of our study population was 52 years. The median overall survival(OS)of the Her 2 overexpressing cohort was 24.0 months. The 1year, 2year and 3year OS of the cohort without brain metastases was 95%, 90.6% and 82% respectively. Breast cancer specific median survival of the Her 2 overexpressing cohort after diagnosis of brain metastases was 5.06 months (Range 0.1- 17.64 months). It was observed that post development of brain metastases, 6 out of 20 patients (30%) had a survival beyond 6 months (Range 6.3 to 17.6 months) and 4 out of 20 (20%) had survived beyond 12 months. Two patients had undergone stereotactic radiosurgery and both of them survived beyond 1 year. On univariate analyses it was found that presence of estrogen receptor positivity was associated with a better outcome, which was statistically significant (P = 0.038). We also observed that Breast Specific Graded Prognostic assessment (BS-GPA) score of more than 2.5 had a trend towards better outcome(P = 0.49). Three out of 4 patients, who survived beyond 1 year after development of brain metastases had a BS-GPA score more than 2.5. Age, menopausal status and number of extracranial metastases were not found to have an impact on survival. Conclusions: Estrogen positivity and BS-GPA score of more than 2.5 are associated with improved survival in patients of Her2 overexpressing breast cancer with brain metastases. This subgroup of patients also benefits with novel approaches like stereotactic radiosurgery for better control of intra cerebral disease. Legal entity responsible for the study: HCG Manavata Cancer Centre. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Are Rural Residence and Poverty Independent Risk Factors for Chronic Obstructive Pulmonary Disease in the United States?
Authors: Ran Wei
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

mortality in the United States (1) and share the goal of improving our understanding of the burden of HP and increasing our awareness of this disease to improve diagnosis and treatment.HP is assuredly a complex, multifaceted lung disease, involving both genetic and environmental risk factors.We agree that the racial differences observed in our study are not solely due to genetic factors.As noted in our DISCUSSION, the contribution of specific exposures is an important but unmeasured variable in our study, and region-specific variations in HP mortality are almost certainly affected by differences in occupational exposure across states.However, regardless of ethnicity/race confounding bias by workplace exposure, genetic variation (which can be related to and differ by race) is likely one of the many risk factors that act together to cause disease and should be considered when interpreting epidemiological data.For example, significant ethnic/racial differences have been described in idiopathic pulmonary fibrosis that may be related to genetic differences (2), and differences in specific gene polymorphisms associated with susceptibility to HP have been observed both between groups with different ethnic backgrounds and within ethnic/racial groups (3-5).Further work is needed to fully understand the role of genetic variation in the molecular and cellular processes, clinical characteristics, and outcomes of HP.We certainly agree that occupational exposures are an important contributor to the overall burden of HP in the United States and that they should always be considered in both individual and population studies.Since the 1980s, various agricultural activities, including crop and animal farming, have been the most frequently recorded industries and occupations on death certificates for individuals with HP.However, when studying the role of occupation, an important limitation of the National Occupational Mortality Surveillance database is that less than half of the states provide data on the usual industry and occupation of decedents (limiting generalizability).Importantly, in contrast to workrelated HP, nonoccupational HP cases are not reportable and therefore are likely undercounted and underrepresented in assessments of the relative contribution of occupational and nonoccupational exposures responsible for HP cases nationwide (6).We hope that the insight gained from our study and the complementary data of Hall and colleagues will serve as a call to state health department officials and federal agencies to revise key policies regarding disease surveillance programs, risk management, and enforcement of exposure limits, particularly in the agricultural sectors, in an effort to reduce the impact of HP in the country.
ENDOSCOPIC RESECTION OF ADVANCED AMPULLARY ADENOMAS: OUTCOMES OF A SINGLE-CENTER RETROSPECTIVE STUDY
Authors: B Miutescu, V Mercea, A Groza, I Ratiu, A Tantau, M Tantau
Journal: Endoscopy (2019)

Ampullary adenomas have a potential of malignant transformation, so complete removal is essential for curative therapy. Endoscopic resection should only be performed in patients without evidence of invasive cancer. This study aims to evaluate the outcome of endoscopic resection of ampullary adenomas in a tertiary endoscopy department.
Reply to: “Normothermic regional perfusion – What is the benefit?”
Authors: Amelia J. Hessheimer, Elisabeth Coll, Patricia Ruíz, Mikel Gastaca, José Ignacio Rivas, Manuel Gómez, Belinda Sánchez, Julio Santoyo, Pablo Ramírez, Pascual Parrilla, Luis Miguel Marín, Miguel Ángel Gómez-Bravo, Juan Carlos García-Valdecasas, Javier López-Monclús, Andrea Boscá, Rafael López-Andújar, Yiliam Fundora-Suárez, Jesús Villar, Álvaro García-Sesma, Carlos Jiménez, Gonzalo Rodríguez-Laíz, Laura Lladó, Juan Carlos Rodríguez, Manuel Barrera, Ramón Charco, Jose Ángel López-Baena, Javier Briceño, Fernando Pardo, Gerardo Blanco, David Pacheco, Beatriz Domínguez-Gil, Víctor Sánchez Turrión, Constantino Fondevila
Journal: Journal of Hepatology (2019)
LIGATION-ASSISTED ENDOSCOPIC MUCOSAL RESECTION (EBL-EMR) AS A SAFE ALTERNATIVE FOR THE RESECTION OF A FLAT DUODENAL ADENOMA IN A CIRRHOTIC PATIENT WITH ECTOPIC DUODENAL VARICES
Authors: G Tribonias, G Kechagias, D Moschovis, E Zacharopoulou, I Giotis, M Palatianou, G Penesis, I Internos, M Tzouvala
Journal: Endoscopy (2019)

Duodenal lesions not involving the major duodenal papilla can be removed with a variety of EMR techniques, but carries an increased risk of bleeding and perforation because the duodenum has increased vascularity and a thin wall.
Anti-inflammatory treatment and inhibition of B-cell activation in a nude mouse model of human breast cancer
Authors: F. Fernandez Madrid, M.-C. Maroun, M. Long
Journal: Annals of Oncology (2019)

Background: The objective of this work was to demonstrate that the concerted action of tumor-associated antigens [TAAs] and inflammatory cytokines inflict autoimmune damage to the breast creating a chronic inflammatory milieu that promotes breast cancer [BC] progression. Methods: We immunoscreened a T7 cDNA library constructed from mRNA extracted from BC tumors developing in untreated nude mice and performed PCR, sequence determination and homology searches using BLAST AND BLAT to detect signal transduction molecules involved in creating a chronic inflammatory milieu leading to BC progression in the DCIS.com mouse xenograft model of BC. We treated BC developing in the xenograft model with rituximab and dexamethasone. We performed immunohistochemistry [IHC] to monitor the evolution of the human BC developing in the DCIS.com mouse model. Results: Breast tumor tissue developing in the xenograft model of BC showed deposition of IgG and complement components C1, C2, C3, C4, C5-C9 on breast epithelial and stromal cells and the expression of IL-4, IL-6, IL-17, TNF-alpha and NFkB detected by IHC staining. Immunoscreening a cDNA library identified autoantibodies recognizing multiple human breast epithelial and stromal antigens and the heavy chain and V regions of immunoglobulins IgG1, IgG3, IgM and both light chains, particularly the lambda LC. Rituximab and dexamethasone treatment markedly modified the morphology of developing tumor in BC developing in the xenograft mouse model. Conclusions: These results suggest that autoantibody- and inflammatory cytokine-mediated autoimmune damage, triggered by TAAs creates a chronic inflammatory milieu with generation of pro-inflammatory and tumor promoting signals supporting BC progression. Thus, in addition to being a protagonist in immune-surveillance, the B cell response in BC may have a tumor-promoting effect. The dramatic results of the treatment of the xenograft model of BC with rituximab and dexamethasone illustrates the potential of adding modalities proven successful in the treatment of the RADs to existing treatments for BC. The demonstration of a major role of autoimmunity in BC progression may have a transformative impact on prevention, diagnosis and treatment of BC. Legal entity responsible for the study: Felix Fernandez Madrid. Funding: NIH. Disclosure: All authors have declared no conflicts of interest.
Profil épidémiologique et prise en charge des ulcères bulbaires hémorragiques
Authors: M Oualgouh, Z Bouabane, F Er-Rabie, N Abda, W Khannoussi, G Kharrasse, I Zahi, A El Mekkaoui
Journal: Endoscopy (2019)

La maladie ulcéreuse du bulbe reste un problème de santé publique avec des répercussions socio-économiques lourdes de part sa fréquence et ses complications inhérentes notamment hémorragiques. Le but de notre étude était de préciser les caractéristiques épidémiologiques, cliniques, endoscopiques, thérapeutiques et pronostiques des ulcères hémorragiques bulbaires.
Abstract 20674: C-C Chemokine Receptor Type 2 (CCR2) Targeted PET Imaging of Early Atherosclerosis
Authors: Hannah Luehmann, Lisa Detering, Robert J Gropler, Yongjian Liu
Journal: Circulation (2017)

Introduction: Atherosclerosis is a chronic inflammatory process with many unmet clinical challenges including early detection. During the initiation and progression of plaque, chemokines and their ...
Genomic prediction of maize yield across European environmental conditions
Authors: Emilie J. Millet, Willem Kruijer, Aude Coupel-Ledru, Santiago Alvarez Prado, Llorenç Cabrera-Bosquet, Sébastien Lacube, Alain Charcosset, Claude Welcker, Fred van Eeuwijk, François Tardieu
Journal: Nature Genetics (2019)