tbuckley/cabot-search huggingface dataset:
Use of geographically weighted logistic regression to quantify spatial variation in the environmental and sociodemographic drivers of leptospirosis in Fiji: a modelling study
Authors: Helen J Mayfield, John H Lowry, Conall H Watson, Mike Kama, Eric J Nilles, Colleen L Lau
Journal: The Lancet Planetary Health (2018)

<h2>Summary</h2><h3>Background</h3> Leptospirosis is a globally important zoonotic disease, with complex exposure pathways that depend on interactions between human beings, animals, and the environment. Major drivers of outbreaks include flooding, urbanisation, poverty, and agricultural intensification. The intensity of these drivers and their relative importance vary between geographical areas; however, non-spatial regression methods are incapable of capturing the spatial variations. This study aimed to explore the use of geographically weighted logistic regression (GWLR) to provide insights into the ecoepidemiology of human leptospirosis in Fiji. <h3>Methods</h3> We obtained field data from a cross-sectional community survey done in 2013 in the three main islands of Fiji. A blood sample obtained from each participant (aged 1–90 years) was tested for anti-<i>Leptospira</i> antibodies and household locations were recorded using GPS receivers. We used GWLR to quantify the spatial variation in the relative importance of five environmental and sociodemographic covariates (cattle density, distance to river, poverty rate, residential setting [urban or rural], and maximum rainfall in the wettest month) on leptospirosis transmission in Fiji. We developed two models, one using GWLR and one with standard logistic regression; for each model, the dependent variable was the presence or absence of anti-<i>Leptospira</i> antibodies. GWLR results were compared with results obtained with standard logistic regression, and used to produce a predictive risk map and maps showing the spatial variation in odds ratios (OR) for each covariate. <h3>Findings</h3> The dataset contained location information for 2046 participants from 1922 households representing 81 communities. The Aikaike information criterion value of the GWLR model was 1935·2 compared with 1254·2 for the standard logistic regression model, indicating that the GWLR model was more efficient. Both models produced similar OR for the covariates, but GWLR also detected spatial variation in the effect of each covariate. Maximum rainfall had the least variation across space (median OR 1·30, IQR 1·27–1·35), and distance to river varied the most (1·45, 1·35–2·05). The predictive risk map indicated that the highest risk was in the interior of Viti Levu, and the agricultural region and southern end of Vanua Levu. <h3>Interpretation</h3> GWLR provided a valuable method for modelling spatial heterogeneity of covariates for leptospirosis infection and their relative importance over space. Results of GWLR could be used to inform more place-specific interventions, particularly for diseases with strong environmental or sociodemographic drivers of transmission. <h3>Funding</h3> WHO, Australian National Health & Medical Research Council, University of Queensland, UK Medical Research Council, Chadwick Trust.
Polymorphisms in toll-like receptors identify a defective oxidative response and a reduction in the regulatory T cell population in patients with cirrhosis and non-infected ascites
Authors: P. Piñero, O. Juanola, I. Gómez-Hurtado, P. Zapater, E. Caparrós, José Such, J.M. González-Navajas, Rubén Francés
Journal: Journal of Hepatology (2018)
A phase 1/2 study of lenalidomide and bendamustine (LEBEN) in chemorefractory Hodgkin lymphoma.
Authors: Gaetano Corazzelli, Mariangela Saggese, Vincenzo Pavone, Francesco Angrilli, Pier Luigi Zinzani, Michele Spina, Mariapaola Fina, Stefania Crisci, Rosa Calemma, Manuela Arcamone, Emanuela Morelli, Domenico Galati, Ferdinando Frigeri, Rosaria De Filippi, Antonello Pinto
Journal: Journal of Clinical Oncology (2014)

8566 Background: Implementing strategies for Hodgkin lymphoma (HL) patients failing stem cell transplantation (SCT) remains a crucial need. We investigated for the first time safety and efficacy of a combination of lenalidomide and bendamustine (LEBEN), two agents synergistically framing different targets on both neoplastic and microenvironment tumor-supporting cells of HL. Methods: A weekly schedule of bendamustine (60 mg/m2; d 1, 8, 15) plus continuous daily lenalidomide (10, 15, 20 or 25 mg), in a 28-day cycle, was tested in a Bayesian phase 1/2 study (Thall & Cook, Biometrics 2004) defining the optimal lenalidomide dosage through the best efficacy/toxicity trade-off. Response (CR or PR at PET/CT) and toxicity (CTCv3.0 grade >3 lasting >2 weeks) endpoints were assessed at 2 cycles (day +56). Non-progressing patients received additional 4 courses. Results: Seventeen chemorefractory patients [SCT failures n=12 (single auto SCT, n=4; tandem n=3; tandem auto/allo, n=5 ); unresponsive to pre-SCT salvage, n=5] were enrolled in 6 cohorts of 3. Patients [males, 80%; median age 29 years (r,19-56)] had a median of 4 prior therapies (r, 2-9), including brentuximab (n= 5). A median of 5 cycles was delivered to 15 evaluable patients. The primary endpoint analysis at 2 cycles showed response without toxicity in 9 patients (60%), response with toxicity in 2 (13%), neither efficacy and toxicity in 4 (27%), toxicity without response in none. The overall response rate (ORR; CR+PR) was 73% with 6 CRs (40%). After 4 cycles, ORR increased to 12/15 (80%) and CRs to 8/15 (53%). The median PFS was 8.7 months. Response was associated to change in circulating myeloid-derived suppressor and dendritic cells. Most common AEs (71 cycles) were (any grade%/≥G3%) diarrhea (27/3), rash (14/3), neutropenia (72/44), thrombocytopenia (65/24), lymphopenia (88/34). Due to the highly favorable efficacy/toxicity trade-off achieved, the Monitoring Committee proposed 10 mg as the optimal lenalidomide dose for subsequent patients. Conclusions: Continuous lenalidomide with low-dose protracted bendamustine was very active and well tolerated in highly refractory HL patients. Enrollment continues, and updated results with correlative data will be presented. Clinical trial information: NTC01412307.
P346Effect of pharmacological activation of adenosine monophosphate activated kinase (AMPK) on endothelial barrier function, proliferation, and angiogenesis
Authors: N Cevinc, C Troidl, C Tanislav, D Guenduez, C W Hamm, M Aslam
Journal: Cardiovascular Research (2018)

expression of the down-stream proteins including transforming growth factor-b1 (TGF-b1), connective tissue growth factor (CTGF), collagen I and collagen VIII in HCSMCs exposed to AGEs.Conclusions: ASK1/MKKs/p38 MAPK pathway was activated by AGEs, leading to fibrotic response in VSMCs.AGI-1067 reversed this process by maintaining the inactive state of ASK1.
P100Tenascin-C is induced by chronic hypoxia in cardiomyoblasts and exacerbates post myocardial infarction remodeling
Authors: D Santer, I Goncalves, F Nagel, A Kiss, M Hasun, A Baumgartner, C Kaun, K Trescher, J Wojta, B K Podesser
Journal: Cardiovascular Research (2018)
Natural history of patients with compensated cirrhosis and a hepatic venous pressure gradient &gt;20 mmHg: A prospective longitudinal cohort study
Authors: A. Bhardwaj, A. Jindal, V. Arora, V. Rajan, A.S. Bhadoria, G. Kumar, L. Anand, A. Choudhury, S.M. Shasthry, R. Maiwall, M. Kumar, S.K. Sarin
Journal: Journal of Hepatology (2018)
Cardiovascular disease and use of contemporary protease inhibitors: the D:A:D international prospective multicohort study
Authors: Lene Ryom, Jens D Lundgren, Wafaa El-Sadr, Peter Reiss, Ole Kirk, Matthew Law, Andrew Phillips, Rainer Weber, Eric Fontas, Antonella d' Arminio Monforte, Stéphane De Wit, Francois Dabis, Camilla I Hatleberg, Caroline Sabin, Amanda Mocroft
Journal: The Lancet HIV (2018)
Validation of the EUTOS long-term survival score in a recent independent cohort of “real world” CML patients
Authors: Inge G. P. Geelen, Fredrik Sandin, Noortje Thielen, Jeroen J. W. M. Janssen, Mels Hoogendoorn, Otto Visser, Jan J. Cornelissen, Martin Hoglund, Peter E. Westerweel
Journal: Leukemia (2018)
Decentralized care is effective in the management of patients with hepatitis C in a public health care setting: The Punjab model
Authors: R.K. Dhiman, G. Grover, M. Premkumar, S. Rathi, M. Chopra, R. Kaur, S. Satsangi, S. Taneja, A. Duseja
Journal: Journal of Hepatology (2018)
Long-term efficacy and safety of WTX101 in Wilson disease: Data from an ongoing extension of a phase 2 study (WTX101-201)
Authors: K.H. Weiss, F. Askari, P. Ferenci, A. Ala, A. Czlonkowska, D. Nicholl, J. Bronstein, D. Bega, M. Schilsky
Journal: Journal of Hepatology (2018)
Re: Massimiliano Spaliviero, Nicholas E. Power, Katie S. Murray, et al. Intravenous Mannitol Versus Placebo During Partial Nephrectomy in Patients with Normal Kidney Function: A Double-blind, Clinically-integrated, Randomized Trial. Eur Urol 2018;73:53–9
Authors: Deepansh Dalela, Firas Abdollah, Craig Rogers
Journal: European Urology (2018)
Update in Chronic Obstructive Pulmonary Disease 2017
Authors: William Z. Zhang, Kazunori Gomi, Seyed Babak Mahjour, Fernando J. Martinez, Renat Shaykhiev
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Chronic obstructive pulmonary disease (COPD) remains an area of considerable interest among healthcare providers, clinical investigators, and lung biologists, not in small part because of its profound impact on health care, both at present and forthcoming (1).According to the Global Burden of Disease Study, more than 250 million people suffer from COPD worldwide, and about 3 million people died from it in 2016 (2, 3), which places COPD in the top four in causes of death (4).In this Update, we summarize the progress made in 2017 in understanding the pathogenesis and clinical aspects of COPD and discuss how this knowledge can lead to novel therapies.
Consensus recommendations for the diagnosis and clinical management of Rosai-Dorfman-Destombes disease
Authors: Oussama Abla, Eric Jacobsen, Jennifer Picarsic, Zdenka Krenova, Ronald Jaffe, Jean-Francois Emile, Benjamin H. Durham, Jorge Braier, Frédéric Charlotte, Jean Donadieu, Fleur Cohen-Aubart, Carlos Rodriguez-Galindo, Carl Allen, James A. Whitlock, Sheila Weitzman, Kenneth L. McClain, Julien Haroche, Eli L. Diamond
Journal: Blood (2018)
TCTAP C-213 Alcohol Ablation of Interventricular Septum Under Ultrasound with Contrast Guidance for Patient with Hypertrophic Obstructive Cardiomyopathy
Authors: Renat Biktashev, Igor V. Buzaev, Irina E. Nikolaeva, Vladimir V. Plechev, Ilgiz Zagitov, Gulchachak Khalikova, Bogdan Aleksandrovich Oleynik
Journal: Journal of the American College of Cardiology (2018)
Prospective feasibility and safety assessment of surgical biopsy for patients with newly diagnosed diffuse intrinsic pontine glioma
Authors: Nalin Gupta, Liliana C Goumnerova, Peter Manley, Susan N Chi, Donna Neuberg, Maneka Puligandla, Jason Fangusaro, Stewart Goldman, Tadanori Tomita, Tord Alden, Arthur DiPatri, Joshua B Rubin, Karen Gauvain, David Limbrick, Jeffrey Leonard, J Russel Geyer, Sarah Leary, Samuel Browd, Zhihong Wang, Sandeep Sood, Anne Bendel, Mahmoud Nagib, Sharon Gardner, Matthias A Karajannis, David Harter, Kanyalakshmi Ayyanar, William Gump, Daniel C Bowers, Bradley Weprin, Tobey J MacDonald, Dolly Aguilera, Barunashish Brahma, Nathan J Robison, Erin Kiehna, Mark Krieger, Eric Sandler, Philipp Aldana, Ziad Khatib, John Ragheb, Sanjiv Bhatia, Sabine Mueller, Anu Banerjee, Amy-Lee Bredlau, Sri Gururangan, Herbert Fuchs, Kenneth J Cohen, George Jallo, Kathleen Dorris, Michael Handler, Melanie Comito, Mark Dias, Kellie Nazemi, Lissa Baird, Jeff Murray, Neal Lindeman, Jason L Hornick, Hayley Malkin, Claire Sinai, Lianne Greenspan, Karen D Wright, Michael Prados, Pratiti Bandopadhayay, Keith L Ligon, Mark W Kieran
Journal: Neuro-Oncology (2018)

Abstract Background Diagnosis of diffuse intrinsic pontine glioma (DIPG) has relied on imaging studies, since the appearance is pathognomonic, and surgical risk was felt to be high and unlikely to affect therapy. The DIPG Biology and Treatment Study (DIPG-BATS) reported here incorporated a surgical biopsy at presentation and stratified subjects to receive FDA-approved agents chosen on the basis of specific biologic targets. Methods Subjects were eligible for the trial if the clinical features and imaging appearance of a newly diagnosed tumor were consistent with a DIPG. Surgical biopsies were performed after enrollment and prior to definitive treatment. All subjects were treated with conventional external beam radiotherapy with bevacizumab, and then stratified to receive bevacizumab with erlotinib or temozolomide, both agents, or neither agent, based on O6-methylguanine-DNA methyltransferase status and epidermal growth factor receptor expression. Whole-genome sequencing and RNA sequencing were performed but not used for treatment assignment. Results Fifty-three patients were enrolled at 23 institutions, and 50 underwent biopsy. The median age was 6.4 years, with 24 male and 29 female subjects. Surgical biopsies were performed with a specified technique and no deaths were attributed to the procedure. Two subjects experienced grade 3 toxicities during the procedure (apnea, n = 1; hypertension, n = 1). One subject experienced a neurologic deficit (left hemiparesis) that did not fully recover. Of the 50 tumors biopsied, 46 provided sufficient tissue to perform the study assays (92%, two-stage exact binomial 90% CI: 83%–97%). Conclusions Surgical biopsy of DIPGs is technically feasible, associated with acceptable risks, and can provide biologic data that can inform treatment decisions.
A single injection of crystallizable fragment domain–modified antibodies elicits durable protection from SHIV infection
Authors: Rajeev Gautam, Yoshiaki Nishimura, Natalie Gaughan, Anna Gazumyan, Till Schoofs, Alicia Buckler-White, Michael S. Seaman, Bruce J. Swihart, Dean A. Follmann, Michel C. Nussenzweig, Malcolm A. Martin
Journal: Nature Medicine (2018)

In the absence of an effective and safe vaccine against HIV-1, the administration of broadly neutralizing antibodies (bNAbs) represents a logical alternative approach to prevent virus transmission. Here, we introduced two mutations encoding amino acid substitutions (M428L and N434S, collectively referred to as ‘LS’) into the genes encoding the crystallizable fragment domains of the highly potent HIV-specific 3BNC117 and 10-1074 bNAbs to increase their half-lives and evaluated their efficacy in blocking infection following repeated low-dose mucosal challenges of rhesus macaques (Macaca mulatta) with the tier 2 SHIVAD8-EO. A single intravenous infusion of 10-1074-LS monoclonal antibodies markedly delayed virus acquisition for 18 to 37 weeks (median, 27 weeks), whereas the protective effect of the 3BNC117-LS bNAb was more modest (provided protection for 11–23 weeks; median, 17 weeks). Serum concentrations of the 10-1074-LS monoclonal antibody gradually declined and became undetectable in all recipients between weeks 26 and 41, whereas the 3BNC117-LS bNAb exhibited a shorter half-life. To model immunoprophylaxis against genetically diverse and/or neutralization-resistant HIV-1 strains, a combination of the 3BNC117-LS plus 10-1074-LS monoclonal antibodies was injected into macaques via the more clinically relevant subcutaneous route. Even though the administered mixture contained an amount of each bNAb that was nearly threefold less than the quantity of the single monoclonal antibody in the intravenous injections, the monoclonal antibody combination still protected macaques for a median of 20 weeks. The extended period of protection observed in macaques for the 3BNC117-LS plus 10-1074-LS combination could translate into an effective semiannual or annual immunoprophylaxis regimen for preventing HIV-1 infections in humans. Long-lived antibodies that can prevent viral infection of monkeys for 6 months may be a future alternative to an HIV vaccine.
The impact of initial antibiotic treatment failure: Real-world insights in healthcare-associated or nosocomial pneumonia
Authors: Kellie Ryan, Sudeep Karve, Pascale Peeters, Elisa Baelen, Danielle Potter, Sonia Rojas-Farreras, Esther Pascual, Jesús Rodríguez-Baño
Journal: Journal of Infection (2018)
P265Functional characterization of a LQT3 mutation located in the PY motif of the cardiac sodium channel associated with altered channel ubiquitylation
Authors: S Casini, V Portero, J S Rougier, M Albesa, G A Marchal, W K Chung, C R Bezzina, H Abriel, C A Remme
Journal: Cardiovascular Research (2018)

Despite more than 100 years of ECG history, several basic relations between myocardial electrophysiology and ECG parameters are still lacking.In this study, we assessed a relation between the myocardium activation time and the QRS complex width depending on several myocardial physiological features, such as the cellular electrophysiological heterogeneity and tissue anisotropy, and the location of excitation source in the tissue.We have developed three personalized computer models of the human heart and the torso for patients with implanted CRT devices.The models are based on computed tomography clinical data.They take into account the ventricular geometry, fiber structure and tissue anisotropy due to different conductivity along and across the fibers, and use detailed cellular ionic models for human cardiomyocytes with accounting for regional cellular heterogeneity.The models were verified against clinical data on ECG recorded from 240 leads on the body surface (Fig. 1) and used to evaluate the sensitivity of simulated ECG to variations in some model parameters.We found a linear correlation between myocardium activation time and the QRS complex width.This ECG parameter was 20-30 ms longer than activation time in simulations with a varied location of the excitation point source within the 17th segmental model (Bull's eye) of the left ventricle (Fig. 23).We also found the importance of the myocardial anisotropy for ECG patterns but showed no effect of the apicobasal cellular heterogeneity on the T-wave genesis in the paced heart.Our results suggest that ECG depends on the combination of myocardial structure, regional electrophysiological heterogeneity, and activation sequence, which are tightly coordinated in the normal heart.In the paced heart the coordination is usually disturbed which is reflected in the change in the ECG patterns and different sensitivity of the ECG parameters to the myocardial properties.
Impact of infectious diseases on population health using incidence-based disability-adjusted life years (DALYs): results from the Burden of Communicable Diseases in Europe study, European Union and European Economic Area countries, 2009 to 2013
Authors: Alessandro Cassini, Edoardo Colzani, Alessandro Pini, Marie-Josee J Mangen, Dietrich Plass, Scott A McDonald, Guido Maringhini, Alies van Lier, Juanita A Haagsma, Arie H Havelaar, Piotr Kramarz, Mirjam E Kretzschmar
Journal: Eurosurveillance (2018)

Background and aims The Burden of Communicable Diseases in Europe (BCoDE) study aimed to calculate disability-adjusted life years (DALYs) for 31 selected diseases in the European Union (EU) and European Economic Area (EEA). Methods: DALYs were estimated using an incidence-based and pathogen-based approach. Incidence was estimated through assessment of data availability and quality, and a correction was applied for under-estimation. Calculation of DALYs was performed with the BCoDE software toolkit without applying time discounting and age-weighting. Results: We estimated that one in 14 inhabitants experienced an infectious disease episode for a total burden of 1.38 million DALYs (95% uncertainty interval (UI): 1.25–1.5) between 2009 and 2013; 76% of which was related to the acute phase of the infection and its short-term complications. Influenza had the highest burden (30% of the total burden), followed by tuberculosis, human immunodeficiency virus (HIV) infection/AIDS and invasive pneumococcal disease (IPD). Men had the highest burden measured in DALYs (60% of the total), adults 65 years of age and over had 24% and children less than 5 years of age had 11%. Age group-specific burden showed that infants (less than 1 year of age) and elderly people (80 years of age and over) experienced the highest burden. Conclusions: These results provide baseline estimates for evaluating infectious disease prevention and control strategies. The study promotes an evidence-based approach to describing population health and assessing surveillance data availability and quality, and provides information for the planning and prioritisation of limited resources in infectious disease prevention and control.
Electrospun nanofibers as a wound dressing for treating diabetic foot ulcer
Authors: Yan Liu, Shiya Zhou, Yanlin Gao, Yinglei Zhai
Journal: Asian Journal of Pharmaceutical Sciences (2018)

Diabetes is one of the most prevalent diseases in the world with high-mortality and complex complications including diabetic foot ulcer (DFU). It has been reported that the difficulties in repairing the wound related to DFU has much relationship with the wound infection, change of inflammatory responses, lack of extracellular matrix (ECM), and the failure of angiogenesis. Following the development of medical materials and pharmaceutical technology, nanofibers has been developed by electrospinning with huge porosity, excellent humidity absorption, a better oxygen exchange rate, and some antibacterial activities. That is to say, as a potential material, nanofibers must be a wonderful candidate for the DFU treatment with so many benefits. Careful selection of polymers from natural resource and synthetic resource can widen the nanofibrous application. Popular methods applied for the nanofibrous fabrication consist of uniaxial electrospinning and coaxial electrospinning. Furthermore, nanofibers loading chemical, biochemical active pharmaceutical ingredient (API) or even stem cells can be wonderful dosage forms for the treatment of DFU. This review summarizes the present techniques applied in the fabrication of nanofibrous dressing (ND) that utilizes a variety of materials and active agents to offer a better health care for the patients suffering from DFU.
P371Hemodynamics and kinetics of arteries: the influence on thromboembolic complications
Authors: O A Germanova, A V Germanov, N N Kryukov
Journal: Cardiovascular Research (2018)

vivo.In addition, treatment with Fx prevents SMC proliferation and neointima lesion formation.This new factor may hold promise as a novel therapeutic tool to enhance functional EC recovery and prevent neointima formation.
Dysfunctional surface antigen-specific memory B cells accumulate in chronic hepatitis B infection
Authors: A. Burton, L.J. Pallett, L. Mccoy, K. Suveizdyte, O.E. Amin, F. Froghi, B.R. Davidson, U.S. Gill, P.A. Blair, C. Mauri, N. Pelletier, M. Maini
Journal: Journal of Hepatology (2018)