tbuckley/cabot-search huggingface dataset:
West Nile Virus and Other Nationally Notifiable Arboviral Diseases — United States, 2017
Authors: Emily J. Curren, Jennifer Lehman, Jonathan Kolsin, William L. Walker, Stacey W. Martin, J. Erin Staples, Susan L. Hills, Carolyn V. Gould, Ingrid B. Rabe, Marc Fischer, Nicole P. Lindsey
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Arthropodborne viruses (arboviruses) are transmitted to humans primarily through the bites of infected mosquitoes or ticks. West Nile virus (WNV) is the leading cause of domestically acquired arboviral disease in the continental United States (1). Other arboviruses, including Jamestown Canyon, La Crosse, Powassan, St. Louis encephalitis, and eastern equine encephalitis viruses, cause sporadic cases of disease and occasional outbreaks. This report summarizes surveillance data reported to CDC from U.S. states in 2017 for nationally notifiable arboviruses. It excludes dengue, chikungunya, and Zika viruses because, in the continental United States, these viruses are acquired primarily through travel. In 2017, 48 states and the District of Columbia (DC) reported 2,291 cases of domestic arboviral disease, including 2,097 (92%) WNV disease cases. Among the WNV disease cases, 1,425 (68%) were classified as neuroinvasive disease (e.g., meningitis, encephalitis, or acute flaccid paralysis), for a national rate of 0.44 cases per 100,000 population. More Jamestown Canyon and Powassan virus disease cases were reported in 2017 than in any previous year. Because arboviral diseases continue to cause serious illness, maintaining surveillance is important to direct and promote prevention activities.
Abstract 15111: TET2-Driven Clonal Hematopoiesis Predicts Enhanced Response to Canakinumab in the CANTOS Trial: An Exploratory Analysis
Authors: Eric C Svensson, Aviv Madar, Catarina D Campbell, Yunsheng He, Marc Sultan, Margaret L Healey, Katie D’Aco, Anita Fernandez, Clarisse Wache-Mainier, Paul M Ridker, Michael T Beste, Craig T Basson
Journal: Circulation (2018)

Clonal Hematopoiesis of Indeterminate Potential (CHIP) is associated with increased risk of atherosclerotic cardiovascular disease and preclinical work in mice has demonstrated that CHIP due to som...
PK/PD modeling based on mouse xenograft tumor growth inhibition and the correlation to clinical exposure for VEGF/PDGF receptor tyrosine kinase inhibitor AG-013736
Authors: Shinji Yamazaki, Maren L. Grazzini, David Romero, Karin Amundson, Yazdi Pithavala, Dana D. Hu-Lowe
Journal: Cancer Research (2005)

3003  AG-013736 is a potent and selective VEGF/PDGF RTK inhibitor that is being evaluated in phase II clinical trials as an oral drug for its anti-cancer activity. Preclinically, the compound inhibited vascular endothelial cell proliferation, migration, survival and induced apoptosis. The compound dose-dependently inhibited tumor growth and metastasis in numerous xenograft and syngeneic models in mice. The in vivo activity of the agent was associated with the inhibition of tissue VEGFR2 and PDGFRβ phosphorylation, reduction of microvessel density and vascular permeability. We also observed that the magnitude of the reduction of these pharmacodynamic endpoints generally correlated with the plasma exposure of the agent. Here we report the quantitative assessment of the relationship between plasma concentrations of AG-013736 and human xenograft tumor growth inhibition (TGI) by the PK/PD modeling. Mice bearing human colon carcinoma MV522 tumors were treated with AG-013736 via either the PO dosing (BID) or continuous infusion across a wide range of doses/concentrations. Dose-dependent and saturable tumor growth inhibition was observed under both treatment regimens. Plasma concentrations collected at various time points of treatment were analyzed by LC/MS/MS using the electronic ionization method. An EC50,SS of 12 ng/ml was estimated from the continuous infusion TGI and the corresponding steady state plasma concentrations of AG-013736. A naive-pooled PK analysis was used to estimate the PK parameters of the compound for each oral dose level using the one-compartment model. Indirect response PK/PD modeling for tumor growth inhibition produced by oral dosing was performed using the estimated PK parameters. The EC50,PO derived by this approach was similar to EC50,SS. Based on the clinical PK parameters and the parameters from the mouse PK/PD modeling, human PK/PD simulation was performed to investigate clinical dose projection. The relationship between the simulated human PK/PD results and the actual clinical PK/PD will be discussed. This line of research emphasizes the complexity of PK/PD modeling and the necessity of understanding and conducting the appropriate preclinical PK/PD studies in order to better aid clinical dose projection for the development of anti-cancer agents.
Insulin degludec, an ultra-longacting basal insulin, versus insulin glargine in basal-bolus treatment with mealtime insulin aspart in type 2 diabetes (BEGIN Basal-Bolus Type 2): a phase 3, randomised, open-label, treat-to-target non-inferiority trial
Authors: Alan J Garber, Allen B King, Stefano Del Prato, Seamus Sreenan, Mustafa K Balci, Manuel Muñoz-Torres, Julio Rosenstock, Lars A Endahl, Ann Marie Ocampo Francisco, Priscilla Hollander
Journal: The Lancet (2012)
Importance of Mcl-1 for Alveolar Macrophage Apoptosis–associated Bacterial Killing
Authors: Heather W. Stout-Delgado
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

This study throws us a few more questions in addition to some of the answers it provided.As stated above, it would be interesting to explore whether higher LBMI in adolescence is a predictor for slow decline in lung function, thereby reducing the risk of adulthood respiratory disorders.Could lifestyle modifications that reduced fat mass and the FMI trajectory alter decline in lung function in later life?Does the variable strength of association of FMI to lower lung function between boys and girls demonstrate the preprogrammed risk of COPD in adult men to be higher than in women?Are there specific factors that influence lung function through the adolescent growth phase?An individual might be endowed with high or low lung function, but it appears to be within his or her own ability to avoid losing lung function by maintaining a healthy FMI.The public health implications are clear: maintain a healthy body composition with lower FMI to preserve adult lung function and reduce the risk of chronic respiratory disease.
REVIEW OF THE GERMAN DERMATOLOGICAL LITERATURE 1968
Authors: B.-R. BALDA, R. BREIT
Journal: British Journal of Dermatology (1970)

Journal Article REVIEW OF THE GERMAN DERMATOLOGICAL LITERATURE 1968 Get access B.‐R. BALDA, B.‐R. BALDA Dermatological Department of the Ludwig‐Maximilians University, Munich. Director: Professor O. Braun‐Falco Search for other works by this author on: Oxford Academic Google Scholar R. BREIT R. BREIT Dermatological Department of the Ludwig‐Maximilians University, Munich. Director: Professor O. Braun‐Falco Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 83, Issue 4, 1 October 1970, Pages 506–512, https://doi.org/10.1111/j.1365-2133.1970.tb15088.x Published: 01 October 1970
P077 Dysregulated miR-125a promotes joint angiogenesis through enhanced glycolysis
Authors: SM Wade, N Ohnesorge, H McLaouglin, M Biniecka, T McGarry, M Canavan, DJ Veale, B Kennedy, U Fearon
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Post-doctoral fellow. <h3>Introduction</h3> Psoriatic arthritis (PsA) is characterised by an early vascular phase essential for pannus growth, immune responses and disease progression. Recently, numerous studies have highlighted the emerging importance of endothelial cell (EC) metabolism in disease. Herein, we propose microRNA, miR-125, modulates EC bioenergetics and orchestrates joint angiogenesis as characterised by <i>ex-vivo</i> associations, <i>in-vitro</i> assays and novel CRISPR/cas9 <i>in-vivo</i> zebrafish models. <h3>Objectives</h3> To elucidate the role of miR-125a and endothelial cell metabolism in dysfunctional angiogenesis in PsA. <h3>Methods</h3> MiRNA levels were quantified in synovial tissue and compared to macroscopic synovial vascularity. HUVECs were transfected with anti-miR-125a for 24 hour and tube formation assays, transwell invasion, wound repair and gene expression analysis performed. Real-time analysis of anti-miR-125 treated ECs metabolism was assessed using the XF-24 Extracellular Flux Analyzer (Seahorse Bioscience). Metabolism markers (GAPDH/PKM2/GLUT1/ATP) were assessed <i>ex vivo</i> by immunohistochemistry. <i>In vivo,</i> miR-125a CRISPR/Cas9-based knock-out zebrafish were generated and vascular development monitored. Finally, miR-125a-/- ECs and zebrafish embryos were treated with an inhibitor of PFKFB3, 3PO. <h3>Results</h3> Synovial expression of miR-125 was significantly decreased in PsA versus OA synovial tissue, levels of which were associated with macroscopic and microscopic synovial vascularity. Decreased expression of miR-125a in HMVEC resulted in increased tube formation, invasion and migration properties. Inhibition of miR-125 promoted a metabolic shift towards glycolysis with parallel changes at the gene level. <i>Ex vivo</i>, increased vascular expression of glycolytic markers was observed in PsA versus OA synovial tissue. <i>In vivo</i>, miR-125a knockout zebrafish displayed increased vascular sprouting similar to the irregular nature of the vasculature within the PsA synovium. Finally, 3PO significantly inhibited anti-miR-125a-induced mechanism whilst normalising the vascular development of miR-125a<sup>-/-</sup> embryos. <h3>Conclusions</h3> Decreased expression of miR-125 in PsA synovium and <i>in-vivo</i> models was strongly associated pro-angiogenic mechanisms. Elevated glycolysis following miR-125 inhibition enabled ECs to meet the increased energy demands for new vessel formation. Correcting these miRNA deficiencies and their resulting metabolic shift, either by conventional pharmacological or as novel drug targets, may provide therapeutic benefit, especially in early disease. <h3>Disclosure of Interest</h3> None declared.
Current status of the PKHDI region transcription map
Authors: Luiz Fernando Onuchic, L. Furu, Y. Nagasawa, Alicia Lakings, K. Mangasser Stephan, Ellis D. Avner, Klaus Zerres, Lisa M. Guay Woodford, Stefan Somlo, Gregory G. Germino
Journal: Journal of the American Society of Nephrology (2000)
Clinical Cancer Advances 2005: Major Research Advances in Cancer Treatment, Prevention, and Screening—A Report From the American Society of Clinical Oncology
Authors: Roy S. Herbst, Dean F. Bajorin, Harry Bleiberg, Diane Blum, Desirée Hao, Bruce E. Johnson, Robert F. Ozols, George D. Demetri, Patricia A. Ganz, Mark G. Kris, Bernard Levin, Maurie Markman, Derek Raghavan, Gregory H. Reaman, Raymond Sawaya, Lynn M. Schuchter, John W. Sweetenham, Linda T. Vahdat, Everett E. Vokes, Rodger J. Winn, Robert J. Mayer
Journal: Journal of Clinical Oncology (2005)

This year, for the first time, the American Society of Clinical Oncology (ASCO) is publishing Clinical Cancer Advances 2005: Major Research Advances in Cancer Treatment, Prevention, and Screening, an annual review of the most significant clinical research presented or published over the past year across all cancer types. ASCO embarked on this project to provide the public, patients, policymakers, and physicians with an accessible summary of the year's most important research advances. While not intended to serve as a comprehensive review, this report provides a year-end snapshot of research that will have the greatest impact on patient care. As you will read, there is much good news from the front lines of cancer research. These pages report on new chemotherapy regimens that sharply reduce the risk of recurrence for very common cancers; the "coming of age" of targeted cancer therapies; promising studies of drugs to prevent cancer; and improvements in quality of life for people living with the disease, among many other advances. Survival rates for cancer are on the rise, increasing from 50% to 64% over the last 30 years. Cancer still exacts an enormous toll, however. Nearly 1.4 million Americans will be diagnosed this year, and some 570,000 will die of the disease. Clearly, more research is needed to find effective therapies for the most stubborn cancer types and stages. We need to know more about the long-term effects of newer, more targeted cancer therapies, some of which need to be taken over long periods of time. And we need to devote far greater attention to tracking and improving the care of the nearly 10 million cancer survivors in the United States today. Despite these and other challenges, the message of this report is one of hope. Through the dedicated, persistent pursuit of clinical research and participation in clinical trials by people with cancer, we steadily uncover new and better ways of treating, diagnosing, and preventing a disease that touches the lives of so many. I want to thank the Editorial Board members, the Specialty Editors, and the ASCO Cancer Communications Committee for their dedicated work to develop this report, and I hope you find it useful.
Reactive species and pathogen antioxidant networks during phagocytosis
Authors: Lucía Piacenza, Madia Trujillo, Rafael Radi
Journal: The Journal of Experimental Medicine (2019)

The generation of phagosomal cytotoxic reactive species (i.e., free radicals and oxidants) by activated macrophages and neutrophils is a crucial process for the control of intracellular pathogens. The chemical nature of these species, the reactions they are involved in, and the subsequent effects are multifaceted and depend on several host- and pathogen-derived factors that influence their production rates and catabolism inside the phagosome. Pathogens rely on an intricate and synergistic antioxidant armamentarium that ensures their own survival by detoxifying reactive species. In this review, we discuss the generation, kinetics, and toxicity of reactive species generated in phagocytes, with a focus on the response of macrophages to internalized pathogens and concentrating on Mycobacterium tuberculosis and Trypanosoma cruzi as examples of bacterial and parasitic infection, respectively. The ability of pathogens to deal with host-derived reactive species largely depends on the competence of their antioxidant networks at the onset of invasion, which in turn can tilt the balance toward pathogen survival, proliferation, and virulence over redox-dependent control of infection.
Yellow Fever–induced Acute Lung Injury
Authors: Alexandre Todorovic Fabro, Gustavo Gonçalves Engelman, Natasha Nicos Ferreira, Júlia Maranhão Fagundes Velloni, Danillo Lucas Alves Espósito, Benedito Antônio Lopes da Fonseca, Mariângela Ottoboni Brunaldi
Journal: American Journal of Respiratory and Critical Care Medicine (2019)
Neutrophil Gelatinase‐Associated Lipocalin for Assessment of Acute Kidney Injury in Cirrhosis: A Prospective Study
Authors: Patricia Huelin, Elsa Solà, Chiara Elia, Cristina Solé, Alessandro Risso, Rebeca Moreira, Marta Carol, Núria Fabrellas, Octavi Bassegoda, Adrià Juanola, Gloria de Prada, Sonia Albertos, Salvatore Piano, Isabel Graupera, Xavier Ariza, Laura Napoleone, Elisa Pose, Xavier Filella, Manuel Morales‐Ruiz, José Rios, Javier Fernández, Wladimiro Jiménez, Esteban Poch, Ferran Torres, Pere Ginès
Journal: Hepatology (2019)

Kidney biomarkers appear to be useful in differential diagnosis between acute tubular necrosis (ATN) and other types of acute kidney injury (AKI) in cirrhosis, particularly hepatorenal syndrome (HRS‐AKI). Distinction is important because treatment is different. However, kidney biomarkers are still not used in clinical practice. The aim of the current study was to investigate the accuracy of several biomarkers in differential diagnosis of AKI and in predicting kidney outcome and patient survival. This was a prospective study of 320 consecutive cases of AKI in patients hospitalized for decompensated cirrhosis. Evaluation of AKI was made with a diagnostic algorithm that included identification and removal/treatment of precipitating factors and albumin administration (1 g/kg for 2 days) to patients with AKI stage 1B or greater. Urinary neutrophil gelatinase–associated lipocalin (NGAL), monomeric NGAL (mNGAL), interleukin‐18, and standard biomarkers were measured at diagnosis and on days 3, 7, and 14. Of the 320 cases, 153 were hypovolemia‐induced AKI (48%), 93 were HRS‐AKI (29%), 39 were ATN (12%), and 35 were due to miscellaneous causes (11%). Among all biomarkers, urinary NGAL measured at day 3 had the greatest accuracy for differential diagnosis between ATN and other types of AKI (area under the receiver operating characteristic curve, 0.87; 95% confidence interval, 0.78‐0.95). The cutoff with the best predictive accuracy for ATN diagnosis was 220 µg/g creatinine. Progression of AKI during hospitalization was associated with persistently high NGAL levels, and NGAL was an independent predictive factor of AKI progression. Likewise, NGAL was also an independent predictive factor of 28‐day mortality together with Model for End‐Stage Liver Disease score. Conclusion : These results support the use of NGAL in clinical practice within the context of a diagnostic algorithm for differential diagnosis of AKI and outcome prediction in cirrhosis.
Lung disease in <scp>STAT</scp>3 hyper‐IgE syndrome requires intense therapy
Authors: Carolin Kröner, Jens Neumann, Julia Ley‐Zaporozhan, Beate Hagl, Iris Meixner, Benedikt D. Spielberger, Gregor Dückers, Bernd H. Belohradsky, Tim Niehues, Michael Borte, Joseph Rosenecker, Matthias Kappler, Susanne Nährig, Simone Reu, Matthias Griese, Ellen D. Renner
Journal: Allergy (2019)

Abstract Background Pulmonary complications are responsible for high morbidity and mortality rates in patients with the rare immunodeficiency disorder STAT 3 hyper‐IgE syndrome ( STAT 3‐ HIES ). The aim of this study was to expand knowledge about lung disease in STAT 3‐ HIES . Methods The course of pulmonary disease, radiological and histopathological interrelations, therapeutic management, and the outcome of 14 STAT 3‐ HIES patients were assessed. Results The patients’ quality of life was compromised most by pulmonary disease. All 14 patients showed first signs of lung disease at a median onset of 1.5 years of age. Lung function revealed a mixed obstructive‐restrictive impairment with reduced FEV 1 and FVC in 75% of the patients. The severity of lung function impairment was associated with Aspergillus fumigatus infection and prior lung surgery. Severe lung tissue damage, with reduced numbers of ATP‐binding cassette sub‐family A member 3 (ABCA3) positive type II pneumocytes, was observed in the histological assessment of two deceased patients. Imaging studies of all patients above 6 years of age showed severe airway and parenchyma destruction. Lung surgeries frequently led to complications, including fistula formation. Long‐term antifungal and antibacterial treatment proved to be beneficial, as were inhalation therapy, chest physiotherapy, and exercise. Regular immunoglobulin replacement therapy tended to stabilize lung function. Conclusions Due to its severity, pulmonary disease in STAT 3‐ HIES patients requires strict monitoring and intensive therapy.
Abstract 2371: Comparison of repeated minor liver resection and major resection on lung metastasis growth in mice
Authors: Masashi Momiyama, Atsushi Suetsugu, Yasunori Tome, Michael Bouvet, Takashi Chishima, Itaru Endo, Robert M. Hoffman
Journal: Cancer Research (2011)

Abstract Liver resection has traditionally been the first choice treatment for patients presenting with primary and metastatic liver tumor. Many of the factors up-regulated during liver regeneration after a liver resection have been implicated in tumor growth and the extent of the up-regulation of these factors correlate with the degree of liver resection. However, the effects of a major liver resection compared to repeated minor resections on the growth of malignant tumor are unknown. This study examines the effects of liver regeneration on the growth of the lung metastatic tumors in an established mouse model, after major (70%) and repeated minor (35%+35%) liver resection. Experimental lung metastases were established by tail vein injection with the Colon 26 murine adenocarcinoma cell line expressing green fluorescent protein (GFP). Three days after cancer cell injection, groups of mice underwent liver resection (35%+35% vs. 70%). Lung tumor growth was measured by fluorescence imaging with the Olympus OV100 Small Animal Imaging System. Although, major and repeated minor resection removed the same volume of liver parenchyma, the two procedures had very different effects on lung metastases growth: Major resection stimulated lung metastatic growth. In contrast to major resection, repeated minor resection significantly inhibited the growth of metastatic lung tumors. There was no significant difference in liver regeneration between the two groups. These results show that repeated minor resection of liver is much safer regarding tumor stimulation than major resection. The results of this study indicate that when liver resection is necessary, repeated minor liver resection is superior to major liver resection, since repeated minor resection inhibits lung metastasis and major resection stimulates lung metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2371. doi:10.1158/1538-7445.AM2011-2371
Increased ketone body oxidation provides additional energy for the failing heart without improving cardiac efficiency
Authors: Kim L Ho, Liyan Zhang, Cory Wagg, Rami Al Batran, Keshav Gopal, Jody Levasseur, Teresa Leone, Jason R B Dyck, John R Ussher, Deborah M Muoio, Daniel P Kelly, Gary D Lopaschuk
Journal: Cardiovascular Research (2019)

Abstract Aims The failing heart is energy-starved and inefficient due to perturbations in energy metabolism. Although ketone oxidation has been shown recently to increase in the failing heart, it remains unknown whether this improves cardiac energy production or efficiency. We therefore assessed cardiac metabolism in failing hearts and determined whether increasing ketone oxidation improves cardiac energy production and efficiency. Methods and results C57BL/6J mice underwent sham or transverse aortic constriction (TAC) surgery to induce pressure overload hypertrophy over 4-weeks. Isolated working hearts from these mice were perfused with radiolabelled β-hydroxybutyrate (βOHB), glucose, or palmitate to assess cardiac metabolism. Ejection fraction decreased by 45% in TAC mice. Failing hearts had decreased glucose oxidation while palmitate oxidation remained unchanged, resulting in a 35% decrease in energy production. Increasing βOHB levels from 0.2 to 0.6 mM increased ketone oxidation rates from 251 ± 24 to 834 ± 116 nmol·g dry wt−1 · min−1 in TAC hearts, rates which were significantly increased compared to sham hearts and occurred without decreasing glycolysis, glucose, or palmitate oxidation rates. Therefore, the contribution of ketones to energy production in TAC hearts increased to 18% and total energy production increased by 23%. Interestingly, glucose oxidation, in parallel with total ATP production, was also significantly upregulated in hearts upon increasing βOHB levels. However, while overall energy production increased, cardiac efficiency was not improved. Conclusions Increasing ketone oxidation rates in failing hearts increases overall energy production without compromising glucose or fatty acid metabolism, albeit without increasing cardiac efficiency.