tbuckley/cabot-search huggingface dataset:
High transmissibility of norovirus among infants and school children during the 2016/17 season in Osaka, Japan
Authors: Naomi Sakon, Jun Komano, Heidi L. Tessmer, Ryosuke Omori
Journal: Eurosurveillance (2018)

The number of person-to-person transmitted norovirus cases (n = 4,712) in school children in Osaka, Japan, during 2016/17 was the largest since 2012/13. Norovirus outbreaks were reported by 101 schools including 53 nursery schools (1,927 cases), 18 kindergartens (1,086 cases) and 30 elementary schools (1,699 cases). The dominant genotype among outbreaks was GII.P16-GII.2 (57.4%; 58/101), followed by GII.P2-GII.2 (8.9%; 9/101) and GII.P7-GII.6 (5.9%; 6/101). GII.4 was not detected despite dominance in previous years.
Prediction of the severity of allergic reactions to foods
Authors: M. E. Pettersson, G. H. Koppelman, B. M. J. Flokstra‐de Blok, B. J. Kollen, A. E. J. Dubois
Journal: Allergy (2018)

Abstract Background There is currently considerable uncertainty regarding what the predictors of the severity of diagnostic or accidental food allergic reactions are, and to what extent the severity of such reactions can be predicted. Objective To identify predictors for the severity of diagnostic and accidental food allergic reactions and to quantify their impact. Methods The study population consisted of children with a double‐blind, placebo‐controlled food challenge ( DBPCFC )–confirmed food allergy to milk, egg, peanut, cashew nut, and/or hazelnut. The data were analyzed using multiple linear regression analysis. Missing values were imputed using multiple imputation techniques. Two scoring systems were used to determine the severity of the reactions. Results A total of 734 children were included. Independent predictors for the severity of the DBPCFC reaction were age (B = 0.04, P = .001), skin prick test ratio (B = 0.30, P &lt; .001), eliciting dose (B = −0.09, P &lt; .001), level of specific immunoglobulin E (B = 0.15, P &lt; .001), reaction time during the DBPCFC (B = −0.01, P = .004), and severity of accidental reaction (B = 0.08, P = .015). The total explained variance of this model was 23.5%, and the eliciting dose only contributed 4.4% to the model. Independent predictors for more severe accidental reactions with an explained variance of 7.3% were age (B = 0.03, P = .014), milk as causative food (B = 0.77, P &lt; .001), cashew as causative food (B = 0.54, P &lt; .001), history of atopic dermatitis (B = −0.47, P = .006), and severity of DBPCFC reaction (B = 0.12, P = .003). Conclusions The severity of DBPCFC s and accidental reactions to food remains largely unpredictable. Clinicians should not use the eliciting dose obtained from a graded food challenge for the purposes of making risk‐related management decisions.
Transgelin-2 as a therapeutic target for asthmatic pulmonary resistance
Authors: Lei-Miao Yin, Yu-Dong Xu, Ling-Ling Peng, Ting-Ting Duan, Jia-Yuan Liu, Zhijian Xu, Wen-Qian Wang, Nan Guan, Xiao-Jie Han, Hai-Yan Li, Yu Pang, Yu Wang, Zhaoqiang Chen, Weiliang Zhu, Linhong Deng, Ying-Li Wu, Guang-Bo Ge, Shuang Huang, Luis Ulloa, Yong-Qing Yang
Journal: Science Translational Medicine (2018)

A transgelin-2 agonist relaxes airway smooth muscle cells and provides therapeutic advantages for asthma.
Abstract 12114: Effects of an Educational Intervention on Disease Knowledge and Self-care Behaviors of Patients With Heart Failure: A Randomized Controlled Trial
Authors: Boyoung Hwang, Debra K Moser, Kathleen Dracup
Journal: Circulation (2016)

Introduction: In this randomized clinical trial, we tested the effects of an educational intervention designed to improve disease knowledge and self-care behaviors of patients with heart failure (HF). Methods: Patients with HF (n=602; 41% female, age 66.1 ± 12.9 years) were randomized into control (usual care) or 1 of 2 intervention groups: Fluid Watchers LITE (LITE) or Fluid Watchers PLUS (PLUS). Patients in both intervention groups received face-to-face education on HF self-care led by a nurse, and then received either 2 follow-up phone calls (LITE group) or biweekly calls until they demonstrated content competency (PLUS group). The levels of HF knowledge and self-care behaviors were measured with self-report questionnaires at baseline and 3, 12, and 24 months. Data were analyzed using linear mixed-models. Results: The 3 groups were not significantly different in their HF knowledge and self-care at baseline. Significant group-by-time interactions were found in models for knowledge and self-care (Figure). Both intervention groups showed improvement in HF knowledge at 3 months, but the improvement lasted only in the PLUS group throughout 24 months. Both intervention groups exhibited significantly better self-care behaviors at 3 and 12 months compared with the control group. The intervention effects on self-care remained stable in both groups, but were not significant at 24 months. Results were similar when covariates (i.e., socioeconomic characteristics and baseline psychological status) were controlled in the models. Conclusions: The face-to-face educational intervention was effective in improving disease knowledge and self-care behaviors among patients with HF. Both intervention groups showed improvement in knowledge and self-care at 3 months, and their effects on self-care remained significant until 12 months. In addition, the intervention with more follow-up calls resulted in greater and more sustained improvement in knowledge about HF.
Successful digital cholangioscopy removal of a stent-retriever tip migrated into the periphery of the bile duct
Authors: Takeshi Ogura, Atsushi Okuda, Akira Miyano, Nobu Nishioka, Kazuhide Higuchi
Journal: Endoscopy (2018)

Various techniques to dilate occluded uncovered metal stents (UMSs) have been reported [1]. A stent retriever (Soehendra stent retriever, SSR-7; Cook, Tokyo, Japan) can also be used as a dilation device in endoscopic retrograde cholangiopancreatography (ERCP) [2] [3]. Herein, we describe a case in which the tip of a stent retriever migrated into the periphery of the bile duct and was successfully removed using digital cholangioscopy.
The cellular biology underlying immune responses against brain tumors: the in vivo formation and function of immunological synapses, and the polarized secretion of effector cytokines
Authors: Jieping Yang, Nicholas Sanderson, James Curtin, Mariana Puntel, Robert Barrett, Kurt Kroeger, Maria Castro, Pedro Lowenstein
Journal: Cancer Research (2008)

1036   Despite the brain immune privilege, effective anti-tumor immune responses can be generated in a variety of brain tumor models. Our lab has recently shown that effector CD8+ T cells establish characteristic Kupfer-type and non Kupfer-type immunological synapses  in vivo  with adenovirus infected brain astrocytes. Furthermore, IFN-γ and granzyme-B were found to cluster in a polarized fashion at immunological synapses between CD8 +  T cells and infected astrocytes. However, whether immunogical synapses exists between tumor cells and CTLs, and whether they are responsible for the clearance of tumor cells in vivo is unknown. In this study, we have developed an  in vivo  glioma mouse model to follow the direct antigen-specific interactions between CTLs and tumor cells. We have explored the utility of murine GL26 glioma expressing OVA to visualize specific antigen-specific cell-to-cell communication between CD8+ T cells and tumor cells  in vivo . To understand the cellular and molecular basis of anti-tumor T cell responses in brain tumors we are currently characterizing the formation of tumor-antigen specific immunological synapses in vivo. We are characterizing their structure (through immunostaining for TCR, LFA-1, CD8 +  T cells, and markers of tumor cells), and their capacity to segregate effector molecules to the immunological synapses. Further, we are also characterizing the molecular and cellular changes undergone by target tumor cells following T cell attack, and the potential role played therein by small Rho GTPases in mediating survival or demise of brain tumor cells. We believe that understanding the cellular and molecular basis of T cells’-brain tumor interactions will provide better ways of eliminating brain tumors by mounting a systemic anti-tumor specific immune response.
Sensory deprivation after focal ischemia in mice accelerates brain remapping and improves functional recovery through Arc-dependent synaptic plasticity
Authors: Andrew W. Kraft, Adam Q. Bauer, Joseph P. Culver, Jin-Moo Lee
Journal: Science Translational Medicine (2018)

Sensory loss induced by whisker trimming facilitates behavioral recovery after focal cerebral ischemia in mice by accelerating Arc-dependent neuronal remapping into the whisker barrel cortex.
Association of PD-L1 Expression with Tumor-Infiltrating Immune Cells and Mutation Burden in High-Grade Neuroendocrine Carcinoma of the Lung
Authors: Hye Sook Kim, Jeong Hyeon Lee, Soo Jeong Nam, Chan-Young Ock, Jae-Woo Moon, Chong Woo Yoo, Geon Kook Lee, Ji-Youn Han
Journal: Journal of Thoracic Oncology (2018)

The immune microenvironment of high-grade neuroendocrine carcinoma of the lung, including programmed death ligand 1 (PD-L1) expression, has not been well characterized.On the basis of immunohistochemistry (IHC) results, PD-L1 expression on tumor cells (TCs) and tumor-infiltrating immune cells (ICs) was scored as follows: TC0 and IC0 were defined as PD-L1 expression less than 1%, TC1 and IC1 as at least 1% but less than 10%, TC2 and IC2 as 10% or more but less than 50%, and TC3 and IC3 as 50% or more. Phosphatase and tensin homolog (PTEN) IHC was scored as either lost or retained expression. The Ion AmpliSeq Comprehensive Cancer Panel (ThermoFisher Scientific, Waltham, MA) was used to identify mutations in all coding exons of 409 cancer-related genes.A total of 192 patients with large cell neuroendocrine carcinoma (LCNEC) (n = 72) and SCLC (n = 120) were studied. The prevalence of PD-L1 expression on TCs was 15.1% (29 of 192). IC infiltration and PD-L1 expression on ICs were observed in 34.4% of patients (66 of 192) and 31.3% of patients (60 of 192), respectively. The prevalence of IC infiltration and PD-L1 expression on IC were more strongly correlated with LCNEC than with SCLC (57.6% versus 23.3%, p < 0.01; 45.8% versus 22.5%, p < 0.01) and high nonsynonymous mutations (p = 0.05 and .04). PTEN loss was found in 9.5% of patients (18 of 189) and showed no correlation with PD-L1 expression. Progression-free survival was better in patients with IC infiltration than in those without IC infiltration (median 11.3 versus 6.8 months [p < 0.01]) and in patients with PD-L1 expression of IC1/2/3 than in those with expression of IC0 (median 11.3 versus 7.0 months [p = 0.03]).These findings suggest that the PD-1/PD-L1 pathway is activated in the microenvironment of pulmonary high-grade neuroendocrine carcinoma and correlated with a higher mutation burden.
ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Agents targeting lymphoid cells surface antigens [I]: CD19, CD20 and CD52)
Authors: M. Mikulska, S. Lanini, C. Gudiol, L. Drgona, G. Ippolito, M. Fernández-Ruiz, B. Salzberger
Journal: Clinical Microbiology and Infection (2018)
New human combined immunodeficiency caused by interferon regulatory factor 4 (IRF4) deficiency inherited by uniparental isodisomy
Authors: María Bravo García-Morato, Francisco Javier Aracil Santos, Alejandro Contreras Briones, Alfonso Blázquez Moreno, Ángela del Pozo Maté, Ángeles Domínguez-Soto, María José Beato Merino, Lucía del Pino Molina, Juan Torres Canizales, Ana Victoria Marin, Elena Vallespín García, Marta Feito Rodríguez, Diego Plaza López Sabando, Anaïs Jiménez-Reinoso, Yasmina Mozo del Castillo, Francisco José Sanz Santaeufemia, Raúl de Lucas-Laguna, Paula P. Cárdenas, Laura Casamayor Polo, María Coronel Díaz, Mar Valés-Gómez, Ernesto Roldán Santiago, Antonio Ferreira Cerdán, Julián Nevado Blanco, Ángel L. Corbí, Hugh T. Reyburn, José Ramón Regueiro, Eduardo López-Granados, Rebeca Rodríguez Pena
Journal: Journal of Allergy and Clinical Immunology (2018)
Abstract 17224: Diagnostic Accuracy of Invasive Fractional Flow Reserve in Patients With Known Moderate Coronary Artery Stenoses Compared With Dobutamine Stress Echocardiography
Authors: Abdelkrim Ahres, Balázs Jablonkai, Andrea Kenessey, Pál Maurovich-Horvath, Márton Kolossváry, Gábor Rubóczky, Ágnes Oze, Astrid Apor, Béla Nagybaczoni, Bálint Szilveszter, Balázs Czigler, Zsuzsanna D Balogh, Péter Andrássy
Journal: Circulation (2017)

Introduction:  The easy accessibility of invasive coronary angiogram in stable coronary artery disease (SCAD) made fractional flow reserve (FFR) a widely applied functional test for the evaluation of moderate stenoses, although the prognostic value for hard endpoints such as mortality and myocardial infarction is equivocal. There are robust data available confirming the prognostic value of dobutamine stress echocardiography (DSE) for the same hard endpoints. In our prospective trial, we sought to compare the DSE to FFR in patients with stable coronary artery disease.   Methods:  SCAD patients with moderate coronary stenoses (40-80 %, diameter) were investigated both by FFR and DSE. Fractional flow reserve    Results:  From 2014 december to 2016 december 92 patients (56 male, age: 62.3±7.7 years; previous PCI: 42 %; ejection fraction: 55±12.3 %; SYNTAX score: 12.3±7.5) were enrolled with 116 lesions (69 LAD, 20 LCx, 27 RCA). FFR compared to DSE has a diagnostic accuracy, positive predictive value (PPV), negative predictive value (NPV), sensitivity and specificity of 69 %, 35 %; 87 %, 58 % and 72 %, respectively. There was a significant correlation between the FFR value and AMS (r=-0.240; p   Conclusions:  In our prospective trial, significant correlation was found between the FFR values and specific DSE parameters. Fractional flow reserve had an excellent NPV, however the PPV was poor. In SCAD patients with a positive FFR, DSE might be useful to confirm the indication of revascularisation.
Training and Validating a Portable Electronic Nose for Lung Cancer Screening
Authors: Rens van de Goor, Michel van Hooren, Anne-Marie Dingemans, Bernd Kremer, Kenneth Kross
Journal: Journal of Thoracic Oncology (2018)

Profiling volatile organic compounds in exhaled breath enables the diagnosis of several types of cancer. In this study we investigated whether a portable point-of-care version of an electronic nose (e-nose) (Aeonose, [eNose Company, Zutphen, the Netherlands]) is able to discriminate between patients with lung cancer and healthy controls on the basis of their volatile organic compound pattern.In this study, we used five e-nose devices to collect breath samples from patients with lung cancer and healthy controls. A total of 60 patients with lung cancer and 107 controls exhaled through an e-nose for 5 minutes. Patients were assigned either to a training group for building an artificial neural network model or to a blinded control group for validating this model.For differentiating patients with lung cancer from healthy controls, the results showed a diagnostic accuracy of 83% with a sensitivity of 83%, specificity of 84%, and area under the curve of 0.84. Results for the blinded group showed comparable results, with a sensitivity of 88%, specificity of 86%, and diagnostic accuracy of 86%.This feasibility study showed that this portable e-nose can properly differentiate between patients with lung cancer and healthy controls. This result could have important implications for future lung cancer screening. Further studies with larger cohorts, including also more participants with early-stage tumors, should be performed to increase the robustness of this noninvasive diagnostic tool and to determine its added value in the diagnostic chain for lung cancer.
A pragmatic approach for mortality prediction after surgery in infective endocarditis: optimizing and refining EuroSCORE
Authors: N. Fernández-Hidalgo, I. Ferreria-González, J.R. Marsal, A. Ribera, M.L. Aznar, A. de Alarcón, E. García-Cabrera, J. Gálvez-Acebal, G. Sánchez-Espín, J.M. Reguera-Iglesias, J. De La Torre-Lima, J.M. Lomas, C. Hidalgo-Tenorio, N. Vallejo, B. Miranda, A. Santos-Ortega, M.A. Castro, P. Tornos, D. García-Dorado, B. Almirante
Journal: Clinical Microbiology and Infection (2018)
Differences in endoscopic techniques for symptomatic Zenker’s diverticulum
Authors: Stefan Gölder, Juliane Brückner, Alanna Ebigbo, Helmut Messmann
Journal: Endoscopy (2018)

See also: Double incision and snare resection in symptomatic Zenker’s diverticulum: a modification of the stag-beetle knife techniqueEndoscopy 2018; 50(02): 182-182DOI: 10.1055/s-0043-123644
A phase 1 study of ibrutinib in combination with R-ICE in patients with relapsed or primary refractory DLBCL
Authors: Craig S. Sauter, Matthew J. Matasar, Heiko Schoder, Sean M. Devlin, Pamela Drullinsky, John Gerecitano, Anita Kumar, Ariela Noy, Maria L. Palomba, Carol S. Portlock, David J. Straus, Andrew D. Zelenetz, Susan J. McCall, Shoshana T. Miller, Amanda I. Courtien, Anas Younes, Craig H. Moskowitz
Journal: Blood (2018)
Runx1 Deficiency Protects Against Adverse Cardiac Remodeling After Myocardial Infarction
Authors: Charlotte S. McCarroll, Weihong He, Kirsty Foote, Ashley Bradley, Karen Mcglynn, Francesca Vidler, Colin Nixon, Katrin Nather, Caroline Fattah, Alexandra Riddell, Peter Bowman, Elspeth B. Elliott, Margaret Bell, Catherine Hawksby, Scott M. MacKenzie, Liam J. Morrison, Anne Terry, Karen Blyth, Godfrey L. Smith, Martin W. McBride, Thomas Kubin, Thomas Braun, Stuart A. Nicklin, Ewan R. Cameron, Christopher M. Loughrey
Journal: Circulation (2017)

Myocardial infarction (MI) is a leading cause of heart failure and death worldwide. Preservation of contractile function and protection against adverse changes in ventricular architecture (cardiac remodeling) are key factors to limiting progression of this condition to heart failure. Consequently, new therapeutic targets are urgently required to achieve this aim. Expression of the Runx1 transcription factor is increased in adult cardiomyocytes after MI; however, the functional role of Runx1 in the heart is unknown.
UKALL 2011: Randomised Trial Investigating a Short Induction Dexamethasone Schedule for Children and Young Adults with Acute Lymphoblastic Leukaemia
Authors: Nicholas John Goulden, Amy A Kirkwood, John Moppett, Sujith Samarasinghe, Sarah Lawson, Clare Rowntree, Rachael Hough, Rajbir Athwal, Pamela R. Kearns, Ajay Vora
Journal: Blood (2017)
Germline DNA-repair Gene Mutations and Outcomes in Men with Metastatic Castration-resistant Prostate Cancer Receiving First-line Abiraterone and Enzalutamide
Authors: Emmanuel S. Antonarakis, Changxue Lu, Brandon Luber, Chao Liang, Hao Wang, Yan Chen, John L. Silberstein, Danilo Piana, Zhao Lai, Yidong Chen, William B. Isaacs, Jun Luo
Journal: European Urology (2018)
“No deal” Brexit would threaten access to new drugs, Hunt warns
Authors: Gareth Iacobucci
Journal: BMJ (2018)

Jeremy Hunt, England’s health and social care secretary, has admitted that it will be “uniquely damaging” to both the United Kingdom and the European Union if the two sides cannot reach an agreement ensuring that patients can continue to access new drugs.

Appearing before the Commons health select committee on 23 January, Hunt was asked what contingency plans his department had drawn up for a potential “no deal” scenario, which would risk disrupting the supply of medicines to and from the UK.

Hunt told …
Association of Disease Severity With Skin Microbiome and Filaggrin Gene Mutations in Adult Atopic Dermatitis
Authors: Maja-Lisa Clausen, Tove Agner, Berit Lilje, Sofie M. Edslev, Thor Bech Johannesen, Paal Skytt Andersen
Journal: JAMA Dermatology (2018)

Skin microbiome correlates with disease severity for lesional and nonlesional skin, indicating a global influence of atopic dermatitis (AD). A relation between skin microbiome and filaggrin gene (FLG) mutations proposes a possible association between skin microbiome and host genetics.To assess skin and nasal microbiome diversity and composition in patients with AD and compare with healthy controls, and to investigate the microbiome in relation to disease severity and FLG mutations in patients with AD.An observational case-control study of 45 adult healthy controls and 56 adult patients with AD was carried out from January 2015 to June 2015 in a tertiary referral center, Department of Dermatology, Bispebjerg Hospital, Denmark.Bacterial swabs were taken from patients with AD (lesional skin, nonlesional skin, and anterior nares) and from healthy controls (nonlesional skin and anterior nares). Eczema severity was assessed and FLG mutations noted. Bacterial DNA was extracted from swabs, and V3-V4 16S rDNA regions amplified with PCR. Samples were analyzed at Statens Serum Institut September 2015 to September 2016. Bioinformatics analyses of the microbiome were analyzed using R statistical software (version 3.3.1, R Foundation Inc).Skin microbiomes were investigated using next-generation sequencing targeting 16S ribosomal RNA.Microbiome alpha diversity was lower in patients with AD compared with healthy controls in nonlesional skin (effect size, 0.710; 95% CI, 0.27-1.15; P = .002), lesional skin (effect size, 0.728; 95% CI, 0.35-1.33; P = .001), and nose (effect size, 1.111; 95% CI, 0.48-0.94; P < .001). Alpha diversity was inversely correlated with disease severity for lesional (effect size, 0.530; 95% CI, 0.23-1.64; P = .02) and nonlesional skin (effect size, 0.451; 95% CI, 0.04-2.44; P = .04) in patients with AD. Microbiome composition in AD nonlesional skin was linked to FLG mutations.An altered microbiome composition in patients with AD in nonlesional skin, lesional skin, as well as nose, suggests a global influence of AD. Microbiome composition in AD nonlesional skin is associated with FLG mutations, proposing a possible association between the skin microbiome and host genetics.
Wnt-signaling enhances neural crest migration of melanoma cells and induces an invasive phenotype
Authors: Tobias Sinnberg, Mitchell P. Levesque, Jelena Krochmann, Phil F. Cheng, Kristian Ikenberg, Francisco Meraz-Torres, Heike Niessner, Claus Garbe, Christian Busch
Journal: Molecular Cancer (2018)

During embryonic development Wnt family members and bone morphogenetic proteins (BMPs) cooperatively induce epithelial-mesenchymal transition (EMT) in the neural crest. Wnt and BMPs are reactivated during malignant transformation in melanoma. We previously demonstrated that the BMP-antagonist noggin blocked the EMT phenotype of melanoma cells in the neural crest and malignant invasion of melanoma cells in the chick embryo; vice-versa, malignant invasion was induced in human melanocytes in vivo by pre-treatment with BMP-2. Although there are conflicting results in the literature about the role of β-catenin for invasion of melanoma cells, we found Wnt/β-catenin signaling to be analogously important for the EMT-like phenotype of human metastatic melanoma cells in the neural crest and during invasion: β-catenin was frequently expressed at the invasive front of human primary melanomas and Wnt3a expression was inversely correlated with survival of melanoma patients. Accordingly, cytoplasmic β-catenin levels were increased during invasion of melanoma cells in the rhombencephalon of the chick embryo. Fibroblast derived Wnt3a reduced melanoma cell adhesion and enhanced migration, while the β-catenin inhibitor PKF115–584 increased adhesion and reduced migration in vitro and in the chick embryonic neural crest environment in vivo. Similarly, knockdown of β-catenin impaired intradermal melanoma cell invasion and PKF115–584 efficiently reduced liver metastasis in a chick chorioallantoic membrane model. Our observations were accompanied by specific alterations in gene expression which are linked to overall survival of melanoma patients. We present a novel role for Wnt-signaling in neural crest like melanoma cell invasion and metastasis, stressing the crucial role of embryonic EMT-inducing neural crest signaling for the spreading of malignant melanoma.