tbuckley/cabot-search huggingface dataset:
Biomaterial Scaffolds Recruit an Aggressive Population of Metastatic Tumor Cells <i>In Vivo</i>
Authors: Grace G. Bushnell, Tejaswini P. Hardas, Rachel M. Hartfield, Yining Zhang, Robert S. Oakes, Scott Ronquist, Haiming Chen, Indika Rajapakse, Max S. Wicha, Jacqueline S. Jeruss, Lonnie D. Shea
Journal: Cancer Research (2019)

For most cancers, metastasis is the point at which clinical treatment shifts from curative intent to extending survival. Biomaterial implants acting as a synthetic premetastatic niche recruit metastatic cancer cells and provide a survival advantage, and their use as a diagnostic platform requires assessing their relevance to disease progression. Here, we showed that scaffold-captured tumor cells (SCAF) were 30 times more metastatic to the lung than primary tumor (PT) cells, similar to cells derived from lung micrometastases (LUNG). SCAF cells were more aggressive
Increased soluble fms-like tyrosine kinase 1 after ischemia reperfusion contributes to adverse clinical outcomes following kidney transplantation
Authors: Theresa M. Wewers, Anna B. Mayer, Alexander Pfleiderer, Katrin Beul, Rene Schmidt, Barbara Heitplatz, Veerle Van Marck, Ingo Nolte, Hermann Pavenstädt, Stefan Reuter, Marcus Brand, Giovana S. Di Marco
Journal: Kidney International (2019)
Interim Estimates of 2016–17 Seasonal Influenza Vaccine Effectiveness — United States, February 2017
Authors: Brendan Flannery, Jessie R. Chung, Swathi N. Thaker, Arnold S. Monto, Emily T. Martin, Edward A. Belongia, Huong Q. McLean, Manjusha Gaglani, Kempapura Murthy, Richard K. Zimmerman, Mary Patricia Nowalk, Michael L. Jackson, Lisa A. Jackson, Angie Foust, Wendy Sessions, LaShondra Berman, Sarah Spencer, Alicia M. Fry
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

In the United States, annual vaccination against seasonal influenza is recommended for all persons aged ≥6 months (1). Each influenza season since 2004-05, CDC has estimated the effectiveness of seasonal influenza vaccine to prevent influenza-associated, medically attended, acute respiratory illness (ARI). This report uses data, as of February 4, 2017, from 3,144 children and adults enrolled in the U.S. Influenza Vaccine Effectiveness Network (U.S. Flu VE Network) during November 28, 2016-February 4, 2017, to estimate an interim adjusted effectiveness of seasonal influenza vaccine for preventing laboratory-confirmed influenza virus infection associated with medically attended ARI. During this period, overall vaccine effectiveness (VE) (adjusted for study site, age group, sex, race/ethnicity, self-rated general health, and days from illness onset to enrollment) against influenza A and influenza B virus infection associated with medically attended ARI was 48% (95% confidence interval [CI] = 37%-57%). Most influenza infections were caused by A (H3N2) viruses. VE was estimated to be 43% (CI = 29%-54%) against illness caused by influenza A (H3N2) virus and 73% (CI = 54%-84%) against influenza B virus. These interim VE estimates indicate that influenza vaccination reduced the risk for outpatient medical visits by almost half. Because influenza activity remains elevated (2), CDC and the Advisory Committee on Immunization Practices recommend that annual influenza vaccination efforts continue as long as influenza viruses are circulating (1). Vaccination with 2016-17 influenza vaccines will reduce the number of infections with most currently circulating influenza viruses. Persons aged ≥6 months who have not yet been vaccinated this season should be vaccinated as soon as possible.
Socioeconomic Disparities Affect Survival of Classical Hodgkin Lymphoma in a Statewide Cancer Registry Analysis
Authors: Zin W. Myint, Runa Shrestha, Quan Chen, Bin Huang, Amit Goldberg, Reshma Ramlal, Gregory Monohan, Roger A. Fleischman, Roger H. Herzig, Gerhard Carl Hildebrandt, Hayder Saeed
Journal: Blood (2018)
Impaired cough suppression in chronic refractory cough
Authors: Peter S.P. Cho, Hannah V. Fletcher, Richard D. Turner, Caroline J. Jolley, Surinder S. Birring
Journal: European Respiratory Journal (2019)

Functional brain imaging in individuals with chronic cough demonstrates reduced activation in cortical regions associated with voluntary cough suppression. Little is known about the ability of patients with chronic cough to suppress cough. This study aimed to compare the ability to voluntarily suppress cough during inhaled capsaicin challenge in participants with chronic refractory cough with that in healthy controls. In addition, this study aimed to assess the repeatability of capsaicin challenge test with voluntary cough suppression.Participants with chronic refractory cough and healthy controls underwent inhaled capsaicin challenge tests while attempting to suppress their cough responses. After 5 days, either a conventional capsaicin challenge test with no cough suppression attempt, or a repeat test with an attempt at cough suppression was performed. Threshold capsaicin concentrations required to elicit one, two and five coughs were calculated by interpolation. Objective 24-h cough frequency was measured in individuals with chronic refractory cough.Healthy controls were able to suppress capsaicin-evoked cough while participants with chronic refractory cough were not. Geometric mean±sd capsaicin dose thresholds for five coughs with (CS5) and without (C5) suppression attempts were 254.40±3.78 versus 45.89±3.95 µmol·L-1, respectively, in healthy controls (p=0.033) and 3.34±5.04 versus 3.86±5.13 µmol·L-1, respectively, in participants with chronic refractory cough (p=0.922). Capsaicin dose thresholds for triggering five coughs with self-attempted cough suppression were significantly lower in participants with chronic refractory cough than in healthy controls; geometric mean±sd 4.94±4.43 versus 261.10±4.34 µmol·L-1, respectively; mean difference (95% CI) 5.72 (4.54-6.91) doubling doses (p<0.001). Repeatability of cough suppression test in both patients and healthy controls was high; intraclass correlation coefficients of log(CS5) values 0.81 and 0.87, respectively. CS5 was associated with objective cough frequency (ρ=-0.514, p=0.029).Participants with chronic refractory cough were less able to voluntarily suppress capsaicin-evoked cough compared to healthy controls. This may have important implications for the pathophysiology and treatment of chronic cough.
TMIC-35. ASTROCYTE-DEPENDENT ENHANCEMENT OF GLIOBLASTOMA GROWTH AS A CANDIDATE THERAPEUTIC TARGET
Authors: Alessandro Mega, Lina Leiss, Mette Hartmark Nilsen, Nick Tobin, Linda Sleire, Carina Strell, Jianping Liu, Natalia Nekhotiaeva, Anders Eriksson, Sven Nelander, Lene Uhrbom, Cecilia Krona, Daniel Hägerstrand, Per Øyvind Enger, Monica Nistér, Arne Östman
Journal: Neuro-Oncology (2018)

Glioblastoma multiforme (GBM) is a disease with an urgent need for deeper understanding and new therapeutic approaches. As in other solid tumors, the tumor microenvironment (TME) is likely to control growth and sensitivity to treatment. Key components of the TME of GBM include the vasculature, microglia and astrocytes. Whereas GBM vasculature and microglia have been extensively studied, less is known about the potential involvement of astrocytes in GBM biology. In this study, astrocytes were investigated with regard to their effect on glioblastoma growth through in vitro approaches and in an in vivo model. Our studies, using different established GBM cell lines, and patient-derived primary GBM cultures, show that co-cultured astrocytes increase GBM cell number by supporting GBM cell proliferation. Furthermore, orthotopic co-injection of astrocytes and GBM cells in mice leads to reduced survival as compared to GBM cell mono-injection. Gene-expression analyses of mono- or co-cultured astrocytes have identified a GBM-cell-induced astrocyte gene signature. Analyses of two publically available GBM gene expression data set demonstrated that the signature of “GBM-educated” astrocytes was associated with significantly shorter survival. These analyses also indicated differences between molecular subgroups of GBM regarding the signature, such that the mesenchymal subset displayed a higher signature score as compared to the other molecular GBM subtypes. A high-throughput screening of approximately 1200 compounds of the “Prestwick-library” has been performed to identify compounds which specifically block the astrocyte-dependent proliferation of U343MG GBM cells. Following the initial screen, 12 compounds have been validated as specifically acting on GBM growth in co-culture. Two of them have been selected for further studies. In summary, this ongoing study suggests that astrocytes contribute to glioblastoma growth and implies this crosstalk as a candidate target for novel therapies. Clinical relevance of the model system is suggested by the prognostic significance of the signature of GBM-educated astrocytes.
Digital biomarkers for Alzheimer’s disease: the mobile/wearable devices opportunity
Authors: Lampros C. Kourtis, Oliver B. Regele, Justin M. Wright, Graham B. Jones
Journal: npj Digital Medicine (2019)

Alzheimer's Disease (AD) represents a major and rapidly growing burden to the healthcare ecosystem. A growing body of evidence indicates that cognitive, behavioral, sensory, and motor changes may precede clinical manifestations of AD by several years. Existing tests designed to diagnose neurodegenerative diseases, while well-validated, are often less effective in detecting deviations from normal cognitive decline trajectory in the earliest stages of the disease. In the quest for gold standards for AD assessment, there is a growing interest in the identification of readily accessible digital biomarkers, which harness advances in consumer grade mobile and wearable technologies. Topics examined include a review of existing early clinical manifestations of AD and a path to the respective sensor and mobile/wearable device usage to acquire domain-centric data towards objective, high frequency and passive digital phenotyping.
The Lettsomian Lectures on Aseptic Surgery in Theory and Practice: Delivered on February 29th, 1904
Authors: C. B. Lockwood
Journal: BMJ (1904)

ENVIRONMENT AND RESULTS.WHEN the cut edges of the skin are brought together with perfect accuracy, they adhere at once and are an effectual -barrier against air infection.In respect to this rapid ad- 'herence the skin is comparable to the peritoneum.But to secure this advantage the apposition must be perfect and -exact.This point is well understood, but perhaps a word 'may be said with regard to another aid to asepsis which will, in the future, have an extensive use.I refer to the complete and accurate closure of the largest wounds by the transposi- tion of flaps of skin, by undercutting, and by the gliding of extensive portions at the boundaries of the wound.
Prognostic significance of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors
Authors: S.R. Amaral, M. Casal Moura, J. Carvalho, A. Chaves, E. Jesus, G. Sousa
Journal: Annals of Oncology (2019)

Background: Immunotherapy with programmed death receptor-1 (PD-1) antibodies has changed the paradigm of advanced NSCLC treatment. These checkpoint inhibitors showed better outcomes compared with standard treatment but reliable predictive markers are still lacking. High pre-treatment NLR and PLR have been associated with poor prognosis in several tumor types and recent studies suggest a potential role also in NSCLC. We thus conducted this study to evaluate the prognostic significance of NLR and PLR in our patients. Methods: All patients with locally advanced and metastatic NSCLC treated with nivolumab and pembrolizumab from February 2016 to October 2018 were enrolled. NLR and PLR were determined by the division of neutrophils and platelets by lymphocytes in peripheral blood. Kaplan Meier method and Cox proportional hazardous analysis were conducted to assess the impact of NLR, PLR and other clinical factors on overall survival (OS) and progression free survival (PFS). Results: Thirty-two patients were treated, 20 with nivolumab and 12 with pembrolizumab. Median age was 61 (40-82); 63% were male; 91% had an ECOG PS ≤ 2; 37% received ≥ 2 prior systemic therapies and 78% had stage IV disease. Increased NLR or PLR values above mean were independent predictive factors for decreased PFS (11 vs. 6 months, HR 3.33 95%CI 0.97 - 11.3, p = 0.056 and 12 vs. 6 months, HR 3.9 95%CI 1.19 - 12.8, p = 0.025, respectively). NLR and PLR values higher than percentil 25 were predictive factors, when used in combination, for decreased OS (21 vs. 11 months, HR 12.363 95% CI 1.303 - 117.291, p = 0.028 and 13 vs. 11 months, HR 3.9 95%CI 1.19 - 12.8, p = 0.025, respectively). Other clinical factors (i.e. histology, tobacco use, age, gender, ECOG PS, metastatic sites) did not present any implication for OS and PFS, as determined by multivariate analyses. Conclusions: Elevated pre-treatment NLR and PLR are associated with shorter OS and PFS in our cohort independently of other prognostic factors. Our results reinforce the potencial role of these markers as a predictive factor of poor prognosis for NSCLC patients. Prospective studies are warranted to validate these findings. Legal entity responsible for the study: Susana Rocha Amaral. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Cost-Effectiveness of Daratumumab Plus Bortezomib and Dexamethasone Versus Bortezomib Plus Dexamethasone for Treatment of Patients with Multiple Myeloma Who Have Received at Least One Prior Therapy: An Analysis of the Castor Trial
Authors: Eric M Maiese, Christopher N Graham, Emma Hawe, Jean-Gabriel Le Moine, Ivo Abraham, Mekre Senbetta
Journal: Blood (2017)
A doença dos legionarios associada a viagens na Europa : 2003
Authors: K D Ricketts, C Joseph
Journal: Eurosurveillance (2004)

Em 2003, 20 paises notificaram 632 casos de doenca dos legionarios associada a viagens a rede de vigilância EWGLINET. Dos 89 clusters de casos detectados, 35 (39%) nao teriam sido identificados sem o programa EWGLINET. Foram investigados 107 locais e foram notificados 22 sitios turisticos na pagina web de EWGLI. 
A proporcao de casos diagnosticados inicialmente pelo teste da antigenuria na urina foi de 81,2% e foram realisados 48 cultivos positivos. Foram notificados 38 obitos, o que equivale a uma taxa bruta de mortalidade de 6%. 
Pediu-se aos paises participantes que informem o centro coordinador dos casos que tinham apresentado sintomas apos uma viagem no proprio pais de residencia (chamado 'viagem interna') e que recolham amostras dos pacientes para cultivos, cada vez que for possivel.
892. Enhanced Survival of Chondrocytes Over Expressing Insulin-Like Growth Factor I in Equine Cartilage Repair
Journal: Molecular Therapy (2004)

Introduction: Articular cartilage has a limited capacity to heal and the goal of successfully repairing defects remains a great clinical challenge. Cell-based strategies in which chondrocytes are transplanted into a cartilage defect have gained popularity for treatment of human and equine patients.
Safety and efficacy of stopping tenofovir disoproxil fumarate in patients with chronic hepatitis B following at least 8 years of therapy: a prespecified follow-up analysis of two randomised trials
Authors: Maria Buti, David K Wong, Edward Gane, Robert Flisiak, Michael Manns, Kelly Kaita, Harry L A Janssen, Marjoleine Op den Brouw, Belinda Jump, Kathryn Kitrinos, Gerald Crans, John Flaherty, Anuj Gaggar, Patrick Marcellin
Journal: The Lancet. Gastroenterology & hepatology (2019)
The Applications of Radiomics in Precision Diagnosis and Treatment of Oncology: Opportunities and Challenges
Authors: Zhenyu Liu, Shuo Wang, Di Dong, Jingwei Wei, Cheng Fang, Xuezhi Zhou, Kai Sun, Longfei Li, Bo Li, Meiyun Wang, Jie Tian
Journal: Theranostics (2019)

Medical imaging can assess the tumor and its environment in their entirety, which makes it suitable for monitoring the temporal and spatial characteristics of the tumor.Progress in computational methods, especially in artificial intelligence for medical image process and analysis, has converted these images into quantitative and minable data associated with clinical events in oncology management.This concept was first described as radiomics in 2012.Since then, computer scientists, radiologists, and oncologists have gravitated towards this new tool and exploited advanced methodologies to mine the information behind medical images.On the basis of a great quantity of radiographic images and novel computational technologies, researchers developed and validated radiomic models that may improve the accuracy of diagnoses and therapy response assessments.Here, we review the recent methodological developments in radiomics, including data acquisition, tumor segmentation, feature extraction, and modelling, as well as the rapidly developing deep learning technology.Moreover, we outline the main applications of radiomics in diagnosis, treatment planning and evaluations in the field of oncology with the aim of developing quantitative and personalized medicine.Finally, we discuss the challenges in the field of radiomics and the scope and clinical applicability of these methods.
Fevipiprant, a Selective Prostaglandin D-2 Receptor 2 Antagonist, Potently Inhibits Chemotaxis and Cytokine Production by Group 2 Innate Lymphoid Cells
Authors: L Xue, C Hardman, W Chen, P Batty, G Ogg, V J Erpenbeck, D A Sandham
Journal: American Journal of Respiratory and Critical Care Medicine (2018)
ECG Challenge: April 28, 2015
Authors: Philip Podrid
Journal: Circulation (2015)

A 72-year-old man with a history of ulcerative colitis, which has been stable, and hypertension, for which he has been taking an angiotensin-converting enzyme inhibitor and β-blocker, presents to his primary care physician for a routine physical examination.The results of the examination are normal, but a slow pulse rate is noted.An ECG is obtained (A).
Physiology and Predictors of Impaired Gas Exchange in Infants with Bronchopulmonary Dysplasia
Authors: Jenny Svedenkrans, Benjamin Stoecklin, J. Gareth Jones, Dorota A. Doherty, J. Jane Pillow
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Rationale: A sensitive outcome measure for infants with bronchopulmonary dysplasia would facilitate clinical benchmarking and enhance epidemiologic understanding, evaluation of clinical interventions, and outcome prediction.Objectives: Noninvasive assessment of pulmonary gas exchange in preterm infants with and without bronchopulmonary dysplasia to grade disease severity and to identify determinants of impaired gas exchange.Methods: This is a prospective observational study in very preterm infants. Inspired oxygen partial pressure (PiO2) was decreased stepwise to achieve oxygen saturation as measured by pulse oximetry (SpO2) that decreased from 95% to 86%. Right shift, V⋅a/Q⋅, and right–left shunt were derived from the resulting SpO2 versus PiO2 curve and compared with current disease severity classification. Potential determinants of shift, V⋅a/Q⋅, and shunt were identified using principal components analysis and multiple linear regression.Measurements and Main Results: A total of 219 infants with median (interquartile range) gestation of 28 weeks and 0 days (26 weeks and 0 days to 29 weeks and 0 days) had a valid study at 35 weeks and 4 days (34 weeks and 1 day to 39 weeks and 3 days) of postmenstrual age. Shift increased and V⋅a/Q⋅ decreased as severity of bronchopulmonary dysplasia increased. Infants with moderate–severe disease also had increased shunt. Extent of impaired gas exchange overlapped between severity groups. Infants requiring mechanical support but no supplemental oxygen at 36 weeks' postmenstrual age had similar values of shift, V⋅a/Q⋅, and shunt to preterm infants without bronchopulmonary dysplasia. Lower gestation and increased duration of invasive ventilation independently predicted increased shift, decreased V⋅a/Q⋅, and increased shunt. Shift was the most sensitive and specific index of the severity of bronchopulmonary dysplasia.Conclusions: Most infants with bronchopulmonary dysplasia have impaired oxygenation quantified by a simple, sensitive bedside test. Shift of the SpO2/PiO2 curve may be useful for prediction and measurement of preterm infant respiratory outcomes.
Two fifths of GPs want to quit in the next five years, poll finds
Authors: Gareth Iacobucci
Journal: BMJ (2019)

Four in 10 GPs intend to quit general practice in the next five years amid growing workload pressures, a survey1 has suggested.

Researchers at the University of Warwick sent a survey to all 1697 GPs in the Wessex region of England asking for their views on how workload pressures were impacting on their career intentions, receiving 929 responses (a 55% response rate).

The results, published in BMJ Open , reveal that 42% (361) of GPs intend to leave or retire from NHS general practice within the next five years. This compared with 32% (439) of those surveyed in the …
Enhancing the Expression of CFTR Using Antisense Molecules against MicroRNA miR-145-5p
Authors: Alessia Finotti, Jessica Gasparello, Enrica Fabbri, Anna Tamanini, Roberto Corradini, Maria Cristina Dechecchi, Giulio Cabrini, Roberto Gambari
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

group (P = 0.0053), suggesting a directly nephroprotective role of NO.However, no assesment of right heart function and no detailed hemodynamic measurements were presented.To determine both the cardiac and renal protective effects of NO during cardiac surgery and the potential cardio-renal interactions that might occur, we are now conducting a randomized trial in 250 cardiac surgery patients at the Massachusetts General Hospital (Boston, MA) with intraoperative echocardiography and pulmonary artery catheterization.We will measure renal biomarkers, assess pre-and postoperative redox states, and evaluate pre-and postoperative levels of plasma NO metabolomics.The primary endpoint of this ongoing study in Boston is to determine whether NO is effective in the prevention of AKI as defined by Kidney Disease Improving Global Outcomes criteria (ClinicalTrials.govIdentifier: NCT02836899).However, in contrast to our first trial in China in patients primarily with rheumatic heart disease, Americans undergoing heart surgery are generally older and are affected by endothelial dysfunction.Endothelial dysfunction is a condition characterized by impaired endothelial NO synthase.In these patients, the diseased endothelium is unable to provide appropriate vasodilation during and after ischemic events, and is unable to replenish plasma NO after consumption of NO from intravascular hemolysis (5).At present (January 2019), we are halfway through enrollment (n = 125).We believe that the results of this ongoing trial will be able to address the hypothesis of Dr. Coutrot and colleagues.
Influences on allergic mechanisms through gut, lung, and skin microbiome exposures
Authors: Andrea M. Kemter, Cathryn R. Nagler
Journal: Journal of Clinical Investigation (2019)

In industrialized societies the incidence of allergic diseases like atopic dermatitis, food allergies, and asthma has risen alarmingly over the last few decades. This increase has been attributed, in part, to lifestyle changes that alter the composition and function of the microbes that colonize the skin and mucosal surfaces. Strategies that reverse these changes to establish and maintain a healthy microbiome show promise for the prevention and treatment of allergic disease. In this Review, we will discuss evidence from preclinical and clinical studies that gives insights into how the microbiota of skin, intestinal tract, and airways influence immune responses in the context of allergic sensitization.