tbuckley/cabot-search huggingface dataset:
Dibutyl Phthalate Augments Allergen-induced Lung Function Decline and Alters Human Airway Immunology. A Randomized Crossover Study
Authors: Danay Maestre-Batlle, Ryan D. Huff, Carley Schwartz, Neil E. Alexis, Scott J. Tebbutt, Stuart Turvey, Anette K. Bølling, Christopher Carlsten
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: Phthalates are a group of chemicals used in common commercial products. Epidemiological studies suggest that phthalate exposure is associated with development or worsening of allergic diseases such as asthma. However, effects of dibutyl phthalate (DBP) or other phthalates found in high concentrations in indoor air have never been examined in allergic individuals in a controlled exposure setting.Objectives: To investigate the airway effects in humans caused by inhalation of a known concentration of a single phthalate, DBP.Methods: In a randomized crossover study, 16 allergen-sensitized participants were exposed to control air or DBP for 3 hours in an environmental chamber followed immediately by an allergen inhalation challenge. Bronchoalveolar wash and lavage were obtained 24 hours after exposure. Lung function, early allergic response, airway responsiveness, inflammation, immune mediators, and immune cell phenotypes were assessed after DBP exposure.Measurements and Main Results: DBP exposure increased the early allergic response (21.4% decline in FEV1 area under the curve, P = 0.03). Airway responsiveness was increased by 48.1% after DBP exposure in participants without baseline hyperresponsiveness (P = 0.01). DBP increased the recruitment of BAL total macrophages by 4.6% (P = 0.07), whereas the M2 macrophage phenotype increased by 46.9% (P = 0.04). Airway immune mediator levels were modestly affected by DBP.Conclusions: DBP exposure augmented allergen-induced lung function decline, particularly in those without baseline hyperresponsiveness, and exhibited immunomodulatory effects in the airways of allergic individuals. This is the first controlled human exposure study providing biological evidence for phthalate-induced effects in the airways.Clinical trial registered with www.clinicaltrials.gov (NCT02688478).
Impact of Age and Sex on Cardiovascular Magnetic Resonance Measurements
Authors: Benedetta Leonardi, Fabrizio Drago, Christopher A. Caldarone, Nagib Dahdah, Frédéric Dallaire, Christian Drolet, Jasmine Grewal, Edward J. Hickey, Paul Khairy, Gerald Lebovic, Brian W. McCrindle, Syed Najaf Nadeem, Ming-Yen Ng, Edythe B. Tham, Judith Therrien, Alexander Van De Bruaene, Isabelle F. Vonder Muhll, Andrew E. Warren, Kenichiro Yamamura, Michael E. Farkouh, Rachel M. Wald
Journal: JACC. Cardiovascular imaging (2020)

Although cardiovascular magnetic resonance (CMR) imaging measurements are known to differ between sexes and according to age in the normal heart, little is known about measurement variability in patients with congenital heart disease (CHD). Yet, aggregate CMR data, without adjustment for sex or age
Use of Frozen Embryo Transfer During Fertility Treatment and Risk of Childhood Cancer—Reply
Authors: Marie Hargreave, Allan Jensen, Susanne K. Kjaer
Journal: JAMA (2020)

In Reply Drs Parmegiani and Vajta note recent changes in the cryopreservation method from the traditional slow-rate freezing to cryopreservation by vitrification and suggest this may be relevant for the interpretation of our study.1
Intrapulmonary airway smooth muscle is hyperreactive with a distinct proteome in asthma
Authors: Gijs Ijpma, Linda Kachmar, Alice Panariti, Oleg S. Matusovsky, Dara Torgerson, Andrea Benedetti, Anne-Marie Lauzon
Journal: European Respiratory Journal (2020)

Constriction of airways during asthmatic exacerbation is the result of airway smooth muscle (ASM) contraction. Although it is generally accepted that ASM is hypercontractile in asthma, this has not been unambiguously demonstrated. Whether airway hyperresponsiveness (AHR) is the result of increased ASM mass alone or also increased contractile force generation per unit of muscle directly determines the potential avenues for treatment. To assess whether ASM is hypercontractile we performed a series of mechanics measurements on isolated ASM from intrapulmonary airways and trachealis from human lungs. We analysed the ASM and whole airway proteomes to verify if proteomic shifts contribute to changes in ASM properties. We report an increase in isolated ASM contractile stress and stiffness specific to asthmatic human intrapulmonary bronchi, the site of increased airway resistance in asthma. Other contractile parameters were not altered. Principal component analysis (PCA) of unbiased mass spectrometry data showed clear clustering of asthmatic subjects with respect to ASM specific proteins. The whole airway proteome showed upregulation of structural proteins. We did not find any evidence for a difference in the regulation of myosin activity in the asthmatic ASM. In conclusion, we showed that ASM is indeed hyperreactive at the level of intrapulmonary airways in asthma. We identified several proteins that are upregulated in asthma that could contribute to hyperreactivity. Our data also suggest enhanced force transmission associated with enrichment of structural proteins in the whole airway. These findings may lead to novel directions for treatment development in asthma.
Muriel Dorothy Dalby
Authors: Arthur Sun Myint, Jonathan Dalby, Simon Dalby
Journal: BMJ (2020)

Muriel was born in Singapore and attended Grimes Tutorial College, Manchester (c 1943). She studied medicine at the University of Manchester.

She had met her future husband, John Dalby, at primary school in Marple. He promised her then that he would marry her one day—and did so, 20 years later.

Muriel trained as an anaesthetist and worked at Ashton General Hospital, while John was training as a …
Repeat Transcatheter Aortic Valve Replacement for Transcatheter Prosthesis Dysfunction
Authors: Uri Landes, John G. Webb, Ole De Backer, Lars Sondergaard, Mohamed Abdel-Wahab, Lisa Crusius, Won-Keun Kim, Christian Hamm, Nicola Buzzatti, Matteo Montorfano, Sebastian Ludwig, Niklas Schofer, Lisa Voigtlaender, Mayra Guerrero, Abdallah El Sabbagh, Josep Rodés-Cabau, Leonardo Guimaraes, Ran Kornowski, Pablo Codner, Taishi Okuno, Thomas Pilgrim, Claudia Fiorina, Antonio Colombo, Antonio Mangieri, Helene Eltchaninoff, Luis Nombela-Franco, Maarten P.H. Van Wiechen, Nicolas M. Van Mieghem, Didier Tchétché, Wolfgang H. Schoels, Matthias Kullmer, Corrado Tamburino, Jan-Malte Sinning, Baravan Al-Kassou, Gidon Y. Perlman, Haim Danenberg, Alfonso Ielasi, Chiara Fraccaro, Giuseppe Tarantini, Federico De Marco, Guy Witberg, Simon R. Redwood, John C. Lisko, Vasilis C. Babaliaros, Mika Laine, Roberto Nerla, Fausto Castriota, Ariel Finkelstein, Itamar Loewenstein, Amnon Eitan, Ronen Jaffe, Philipp Ruile, Franz J. Neumann, Nicolo Piazza, Hind Alosaimi, Horst Sievert, Kolja Sievert, Marco Russo, Martin Andreas, Matjaz Bunc, Azeem Latib, Rebecca Govdfrey, David Hildick-Smith, Janarthanan Sathananthan, Mark Hensey, Abdullah Alkhodair, Philipp Blanke, Jonathon Leipsic, David A. Wood, Tamim M. Nazif, Susheel Kodali, Martin B. Leon, Marco Barbanti
Journal: Journal of the American College of Cardiology (2020)
Endoscopic ultrasound-guided gallbladder drainage after distension with a high density solution (hyaluronic acid)
Authors: Lucía Medina-Prado, Carolina Mangas-Sanjuan, Belén Martínez-Moreno, Juan Martínez-Sempere, Tyler M. Berzin, José Ramón Aparicio
Journal: Endoscopy (2020)

A 95-year-old woman presented to the emergency department with clinical deterioration and vomiting. An abdominal computed tomography scan showed acute cholecystitis. She was not a candidate for surgery, therefore a percutaneous cholecystostomy was performed. In order to internalize drainage, 3 days later, the decision was made to convert the percutaneous cholecystostomy to internal transmural gallbladder drainage using a lumen-apposing metal stent (LAMS) ([Video 1]). The gallbladder was initially difficult to visualize owing to the presence of a 3 × 2-cm perivesicular abscess ([Fig. 1]).
Abstract B38: Virome assembly and annotation in brain tissue based on next-generation sequencing
Authors: Zihao Yuan, Xiaohua Ye, Ningyan Zhang, Zhiqiang An, Wenjin Zheng
Journal: Cancer Research (2020)

Abstract Glioblastoma multiforme (GBM) is one of the most lethal brain tumors, and the virosphere in brain and its correlation with GBM triggering is controversy. The previous research in brain virosphere was mainly limited to the presence of human cytomegalovirus (HCMV); a comprehensive assessment of the brain virome based on the recently sequenced data and the understanding of the novel sequences that cannot be mapped to the known reference sequences are lacking. Here, we characterized the virome from 111 GBM samples and 57 normal brain samples from 8 projects in SRA database by known and novel viruses in a tested and comprehensive assembly approach. The annotation of those contigs showed most of the viral sequences belongs to the Retroviridae. A novel picornavirus, which was recently discovered from the invertebrate, can be detected in some GBM samples in full genome length. Furthermore, our analysis showed that the herpes virus fragments that are annotated as Epstein-Barr virus (EBV) only exist in the GBM with less than 1% of the EBV whole genome, supporting the absence of herpes virus in GBM. The further analysis showed that the contigs that have no annotations from the known databases may have the antibody properties and antibody epitopes to be the future drug targets. In this study, we characterized the virosphere in GBM and normal brain at a global level, to provide a basis for future GBM research and therapies. Citation Format: Zihao Yuan, Xiaohua Ye, Ningyan Zhang, Zhiqiang An, Wenjin Zheng. Virome assembly and annotation in brain tissue based on next-generation sequencing [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr B38.
Coronavirus Disease 2019 Pneumonia in Immunosuppressed Renal Transplant Recipients: A Summary of 10 Confirmed Cases in Wuhan, China
Authors: Lan Zhu, Nianqiao Gong, Bin Liu, Xia Lu, Dong Chen, Song Chen, Hongge Shu, Ke Ma, Xizhen Xu, Zhiliang Guo, Enfeng Lu, Dongrui Chen, Qinggang Ge, Junchao Cai, Jipin Jiang, Lai Wei, Weijie Zhang, Gang Chen, Zhishui Chen
Journal: European Urology (2020)
Type 2 immunity in the skin and lungs
Authors: Cezmi A. Akdis, Peter D. Arkwright, Marie-Charlotte Brüggen, William Busse, Massimo Gadina, Emma Guttman‐Yassky, Kenji Kabashima, Yasutaka Mitamura, Laura Vian, Jianni Wu, Oscar Palomares
Journal: Allergy (2020)

Abstract There has been extensive progress in understanding the cellular and molecular mechanisms of inflammation and immune regulation in allergic diseases of the skin and lungs during the last few years. Asthma and atopic dermatitis (AD) are typical diseases of type 2 immune responses. interleukin (IL)‐25, IL‐33, and thymic stromal lymphopoietin are essential cytokines of epithelial cells that are activated by allergens, pollutants, viruses, bacteria, and toxins that derive type 2 responses. Th2 cells and innate lymphoid cells (ILC) produce and secrete type 2 cytokines such as IL‐4, IL‐5, IL‐9, and IL‐13. IL‐4 and IL‐13 activate B cells to class‐switch to IgE and also play a role in T‐cell and eosinophil migration to allergic inflammatory tissues. IL‐13 contributes to maturation, activation, nitric oxide production and differentiation of epithelia, production of mucus as well as smooth muscle contraction, and extracellular matrix generation. IL‐4 and IL‐13 open tight junction barrier and cause barrier leakiness in the skin and lungs. IL‐5 acts on activation, recruitment, and survival of eosinophils. IL‐9 contributes to general allergic phenotype by enhancing all of the aspects, such as IgE and eosinophilia. Type 2 ILC contribute to inflammation in AD and asthma by enhancing the activity of Th2 cells, eosinophils, and their cytokines. Currently, five biologics are licensed to suppress type 2 inflammation via IgE, IL‐5 and its receptor, and IL‐4 receptor alpha. Some patients with severe atopic disease have little evidence of type 2 hyperactivity and do not respond to biologics which target this pathway. Studies in responder and nonresponder patients demonstrate the complexity of these diseases. In addition, primary immune deficiency diseases related to T‐cell maturation, regulatory T‐cell development, and T‐cell signaling, such as Omenn syndrome, severe combined immune deficiencies, immunodysregulation, polyendocrinopathy, enteropathy, X‐linked syndrome, and DOCK8, STAT3, and CARD11 deficiencies, help in our understanding of the importance and redundancy of various type 2 immune components. The present review aims to highlight recent advances in type 2 immunity and discuss the cellular sources, targets, and roles of type 2 mechanisms in asthma and AD.
Recombinant Factor VIIa [(rFVIIa) NovoSeven® by Single Dose for Home Treatment of Joint Bleeds in Hemophilia Patients with Inhibitors: A Pilot, Double-Blind Study Versus Standard Multiple Doses of NovoSeven® and an Activated Prothrombin Complex Concentrate [aPCC (FEIBA®)].
Authors: Guy Young
Journal: Blood (2006)
Using social and behavioural science to support COVID-19 pandemic response
Authors: Jay J. Van Bavel, Katherine Baicker, Paulo S. Boggio, Valerio Capraro, Aleksandra Cichocka, Mina Cikara, Molly J. Crockett, Alia J. Crum, Karen M. Douglas, James N. Druckman, John Drury, Oeindrila Dube, Naomi Ellemers, Eli J. Finkel, James H. Fowler, Michele Gelfand, Shihui Han, S. Alexander Haslam, Jolanda Jetten, Shinobu Kitayama, Dean Mobbs, Lucy E. Napper, Dominic J. Packer, Gordon Pennycook, Ellen Peters, Richard E. Petty, David G. Rand, Stephen D. Reicher, Simone Schnall, Azim Shariff, Linda J. Skitka, Sandra Susan Smith, Cass R. Sunstein, Nassim Tabri, Joshua A. Tucker, Sander van der Linden, Paul van Lange, Kim A. Weeden, Michael J. A. Wohl, Jamil Zaki, Sean R. Zion, Robb Willer
Journal: Nature Human Behaviour (2020)
Colorectal cancer triple co-culture spheroid model to assess the biocompatibility and anticancer properties of polymeric nanoparticles
Authors: Tomás Bauleth-Ramos, Tália Feijão, André Gonçalves, Mohammad-Ali Shahbazi, Zehua Liu, Cristina Barrias, Maria José Oliveira, Pedro Granja, Hélder A. Santos, Bruno Sarmento
Journal: Journal of Controlled Release (2020)
Barriers to, and recommendations for, the provision of care and support to children living as AIDS orphans in township communities in South Africa: a cluster analysis
Authors: Sharron Frood
Journal: The Lancet Global Health (2020)

BackgroundOrphanhood is a major consequence of the AIDS pandemic; the total number of people living with HIV in South Africa increased from an estimated 4·72 million in 2002 to 7·03 million by 2017. In South Africa, most children who are orphaned because one or both parents died from AIDS live in township communities. The aim of this study was to identify barriers to, and recommendations for, providing care and support to these vulnerable children.MethodsI undertook in-depth interviews with professionals caring for and supporting children who are AIDS orphans at four primary health care clinics and 12 satellite health care clinics in township communities in Nelson Mandela Bay, South Africa. Interviews were recorded and transcribed verbatim. Primary health care nurses and social workers were selected using criterion-based purposive sampling; snowball sampling was used to select psychologists. I asked participants to make recommendations for how care and support is provided for children who are AIDS orphans living in township communities in South Africa. Data were coded 0 for absent and 1 for present and used the heatmap.2 command in the R package gplots, which uses Euclidean distance to cluster the pattern of participant responses.FindingsBetween April and October, 2013, ten primary health care nurses, eight social workers, and six psychologists were interviewed. Analysis undertaken in September, 2018, identified six clusters illustrating barriers to providing care and support: fundamental barriers such as low morale in professionals; barriers primarily related to legislative and policy frameworks; lack of human and financial resources; grief, high-risk behaviours, and cumbersome bureaucratic processes; poverty; and barriers related to poverty including non-disclosure of HIV status. Recommendations identified fell into the following broad themes: development of resilience of health and social care professionals; development of responses to meet the unique needs of these AIDS orphans; developing, empowering, and capacitating professionals; and facilitating an empowering working environment.InterpretationSignificant clusters emerged from analysis and these identified barriers to, and recommendations for, delivering care could be used to form the cornerstone of an intervention to provide best practice care and support for these vulnerable children.FundingNone
Association of genetic and immuno-characteristics with clinical outcomes in patients with RET-rearranged non-small cell lung cancer: a retrospective multicenter study
Authors: Chang Lu, Xiao-Rong Dong, Jun Zhao, Xu-Chao Zhang, Hua-Jun Chen, Qing Zhou, Hai-Yan Tu, Xing-Hao Ai, Xiao-Feng Chen, Gai-Li An, Jun Bai, Jin-Lu Shan, Yi-Na Wang, Shuan-Ying Yang, Xiang Liu, Wu Zhuang, Hui-Ta Wu, Bo Zhu, Xue-Feng Xia, Rong-Rong Chen, De-Jian Gu, Hua-Min Xu, Yi-Long Wu, Jin-Ji Yang
Journal: Journal of Hematology & Oncology (2020)

Abstract Background Rearranged during transfection ( RET ) has been proven to be a tumorigenic target in non-small cell lung cancers (NSCLCs). In RET -rearranged NSCLCs, molecular features and their impact on prognosis were not well illustrated, and the activity of mainstay therapeutics has not currently been well compared. Methods Patients diagnosed with NSCLCs with RET rearrangements were analyzed for concomitant mutations, tumor mutation burden (TMB), PD-L1 expression, T cell receptor repertoire and clinical outcomes with chemotherapy, immune checkpoint inhibitors (ICIs), and multikinase inhibitors (MKIs). Results Among 129 patients with RET -rearranged NSCLC who were analyzed, 41.1% (53/129) had co-occurring genetic alterations by next-generation sequencing, and concomitant TP53 mutation appeared most frequently (20/53, 37.7%). Patients with concurrent TP53 mutation ( n = 15) had shorter overall survival than those without ( n = 30; median, 18.4 months [95% CI, 8.6–39.1] vs 24.8 months [95% CI, 11.7–52.8]; P &lt; 0.05). Patients with lower peripheral blood TCR diversity ( n = 5) had superior overall survival compared with those with higher diversity ( n = 6; median, 18.4 months [95% CI, 16.9–19.9] vs 4.8 months [95% CI, 4.5–5.3]; P = 0.035). An association with overall survival was not observed for PD-L1 expression nor for tumor mutation burden level. Median progression-free survival was not significantly different across chemotherapy, ICIs, and MKIs (median, 3.5 vs 2.5 vs 3.8 months). For patients treated with ICIs, the disease control rate was 60% (6/10) and the objective response rate was 20% (2/10). Conclusions RET -rearranged lung cancers can be heterogeneous in terms of concomitant genetic alterations. Patients with concurrent TP53 mutation or high peripheral blood TCR repertoire diversity have relatively inferior overall survival in this series. Outcomes with traditional systemic therapies in general are suboptimal.
Percutaneous transcystic cholangioscopy-guided electrohydraulic lithotripsy in a patient with altered surgical anatomy
Authors: Eduardo Rodrigues-Pinto, Pedro Pereira, Guilherme Macedo
Journal: Endoscopy (2020)

A 68-year-old man with a history of Roux-en-Y partial gastrectomy for gastric cancer and pancreatic enucleation for a somatostatin-producing neuroendocrine tumor underwent urgent open cholecystectomy due to acute cholecystitis. Intraoperative choledochoscopy showed a common bile duct (CBD) stone which could not be removed. A transcystic Nelaton tube was placed. One week later, cholangiography confirmed the 10-mm CBD stone was still present. The tube was left in place to allow maturation of the tract for a further procedure, but 20 days later it was accidentally displaced. As percutaneous biliary drainage persisted, the patient was referred to us to try percutaneous transcystic cholangioscopy-guided electrohydraulic lithotripsy. Contrast instilled directly into the percutaneous access confirmed persistence of the tract, which was tortuous and narrowed in the proximal part ([Fig. 1]). Guidewire passage into the CBD was difficult ([Fig. 2]) and was only achieved under contrast guidance with looping of the guidewire and single-operator cholangioscope (Spyglass DS II) assistance. Passage of the cholangioscope into the CBD was possible after gentle dilatation of the proximal part of the tract, and the stone was visualized in the distal part of the CBD ([Fig. 3]). Electrohydraulic lithotripsy was performed under direct visualization with pulverization of the stone ([Fig. 4]; [Video 1]). A 10-Fr double-pigtail plastic stent was left in place for 24 h ([Fig. 5]) to ensure easy access to the CBD in case of any complications. The patient remains well 1 month later.
Correction to: 3rd ESO–ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 3)
Authors: F. Cardoso, A. Costa, E. Senkus, M. Aapro, F. André, C.H. Barrios, J. Bergh, G. Bhattacharyya, L. Biganzoli, M.J. Cardoso, L. Carey, D. Corneliussen-James, G. Curigliano, V. Dieras, N. El Saghir, A. Eniu, L. Fallowfield, D. Fenech, P. Francis, K. Gelmon, A. Gennari, N. Harbeck, C. Hudis, B. Kaufman, I. Krop, M. Mayer, H. Meijer, S. Mertz, S. Ohno, O. Pagani, E. Papadopoulos, F. Peccatori, F. Penault-Llorca, M.J. Piccart, J.Y. Pierga, H. Rugo, L. Shockney, G. Sledge, S. Swain, C. Thomssen, A. Tutt, D. Vorobiof, B. Xu, L. Norton, E. Winer
Journal: Annals of Oncology (2017)

Ann Oncol 2016; 28(1): 16–33 In the original article, author F. Penault-Llorca’s name was incorrectly written as F. Pernault-Llorca. This has been corrected online. 3rd ESO–ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 3)Annals of OncologyVol. 28Issue 1PreviewAdvanced Breast Cancer (ABC) comprises both locally advanced (LABC) and metastatic breast cancer (MBC) [1]. Although treatable, MBC remains an incurable disease with a median overall survival of ∼2–3 years and a 5-year survival of only ∼25% [2–4]. Some more recent series seem to indicate an improvement in median overall survival [5, 6]. Full-Text PDF Open Access
Weak supervision as an efficient approach for automated seizure detection in electroencephalography
Authors: Khaled Saab, Jared Dunnmon, Christopher Ré, Daniel Rubin, Christopher Lee-Messer
Journal: npj Digital Medicine (2020)

Automated seizure detection from electroencephalography (EEG) would improve the quality of patient care while reducing medical costs, but achieving reliably high performance across patients has proven difficult. Convolutional Neural Networks (CNNs) show promise in addressing this problem, but they are limited by a lack of large labeled training datasets. We propose using imperfect but plentiful archived annotations to train CNNs for automated, real-time EEG seizure detection across patients. While these weak annotations indicate possible seizures with precision scores as low as 0.37, they are commonly produced in large volumes within existing clinical workflows by a mixed group of technicians, fellows, students, and board-certified epileptologists. We find that CNNs trained using such weak annotations achieve Area Under the Receiver Operating Characteristic curve (AUROC) values of 0.93 and 0.94 for pediatric and adult seizure onset detection, respectively. Compared to currently deployed clinical software, our model provides a 31% increase (18 points) in F1-score for pediatric patients and a 17% increase (11 points) for adult patients. These results demonstrate that weak annotations, which are sustainably collected via existing clinical workflows, can be leveraged to produce clinically useful seizure detection models.