tbuckley/cabot-search huggingface dataset:
Novel Molecular and Phenotypic Insights into Congenital Lung Malformations
Authors: Daniel T. Swarr, William H. Peranteau, Jennifer Pogoriler, David B. Frank, N. Scott Adzick, Holly L. Hedrick, Mike Morley, Su Zhou, Edward E. Morrisey
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Rationale: Disruption of normal pulmonary development is a leading cause of morbidity and mortality in infants. Congenital lung malformations are a unique model to study the molecular pathogenesis of isolated structural birth defects, as they are often surgically resected.Objectives: To provide insight into the molecular pathogenesis of congenital lung malformations through analysis of cell-type and gene expression changes in these lesions.Methods: Clinical data, and lung tissue for DNA, RNA, and histology, were obtained from 58 infants undergoing surgical resection of a congenital lung lesion. Transcriptome-wide gene expression analysis was performed on paired affected and unaffected samples from a subset of infants (n = 14). A three-dimensional organoid culture model was used to assess isolated congenital lung malformation epithelium (n = 3).Measurements and Main Results: Congenital lung lesions express higher levels of airway epithelial related genes, and dysregulated expression of genes related to the Ras and PI3K–AKT–mTOR (phosphatidylinositol 3-kinase–AKT–mammalian target of rapamycin) signaling pathways. Immunofluorescence confirmed differentiated airway epithelial cell types throughout all major subtypes of congenital lung lesions, and three-dimensional cell culture demonstrated a cell-autonomous defect in the epithelium of these lesions.Conclusions: This study provides the first comprehensive analysis of the congenital lung malformation transcriptome and suggests that disruptions in Ras or PI3K–AKT–mTOR signaling may contribute to the pathology through an epithelial cell-autonomous defect.
Asthma Mortality Among Persons Aged 15–64 Years, by Industry and Occupation — United States, 1999–2016
Authors: Opal Patel, Girija Syamlal, John Wood, Katelynn E. Dodd, Jacek M. Mazurek
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

In 2015, an estimated 18.4 million U.S. adults had current asthma, and 3,396 adult asthma deaths were reported (1). An estimated 11%-21% of asthma deaths might be attributable to occupational exposures (2). To describe asthma mortality among persons aged 15-64 years,* CDC analyzed multiple cause-of-death data† for 1999-2016 and industry and occupation information collected from 26 states§ for the years 1999, 2003, 2004, and 2007-2012. Proportionate mortality ratios (PMRs)¶ for asthma among persons aged 15-64 years were calculated. During 1999-2016, a total of 14,296 (42.9%) asthma deaths occurred among males and 19,011 (57.1%) occurred among females. Based on an estimate that 11%-21% of asthma deaths might be related to occupational exposures, during this 18-year period, 1,573-3,002 asthma deaths in males and 2,091-3,992 deaths in females might have resulted from occupational exposures. Some of these deaths might have been averted by instituting measures to prevent potential workplace exposures. The annual age-adjusted asthma death rate** per 1 million persons aged 15-64 years declined from 13.59 in 1999 to 9.34 in 2016 (p<0.001) among females, and from 9.14 (1999) to 7.78 (2016) (p<0.05) among males. The highest significantly elevated asthma PMRs for males were for those in the food, beverage, and tobacco products manufacturing industry (1.82) and for females were for those in the social assistance industry (1.35) and those in community and social services occupations (1.46). Elevated asthma mortality among workers in certain industries and occupations underscores the importance of optimal asthma management and identification and prevention of potential workplace exposures.
Haptoglobin and Hemopexin Infusion Efficiently Activates the Nrf2/HO-1 Axis and Inhibits Inflammation and Vaso-Occlusion in Murine Sickle Cell Disease
Authors: John D Belcher, Chunsheng Chen, Julia Nguyen, Fuad Abdulla, Phong Nguyen, Hao Nguyen, Ping Zhang, Nathan Brinkman, Gregory M Vercellotti
Journal: Blood (2016)
Targeted and Nontargeted α-Particle Therapies
Authors: Michael R. McDevitt, George Sgouros, Stavroula Sofou
Journal: Annual Review of Biomedical Engineering (2018)

α-Particle irradiation of cancerous tissue is increasingly recognized as a potent therapeutic option. We briefly review the physics, radiobiology, and dosimetry of α-particle emitters, as well as the distinguishing features that make them unique for radiopharmaceutical therapy. We also review the emerging clinical role of α-particle therapy in managing cancer and recent studies on in vitro and preclinical α-particle therapy delivered by antibodies, other small molecules, and nanometer-sized particles. In addition to their unique radiopharmaceutical characteristics, the increased availability and improved radiochemistry of α-particle radionuclides have contributed to the growing recent interest in α-particle radiotherapy. Targeted therapy strategies have presented novel possibilities for the use of α-particles in the treatment of cancer. Clinical experience has already demonstrated the safe and effective use of α-particle emitters as potent tumor-selective drugs for the treatment of leukemia and metastatic disease.
Modulation of IgE and IgG4 with Dietary Treatment of Eosinophilic Esophagitis and Peanut Allergy
Authors: Elizabeth Erwin, Alexander J. Schuyler, Julia A. Cronin, Patrice G. Kruszewski, Lisa J. Workman, Scott P. Commins, Thomas A.E. Platts-Mills
Journal: Journal of Allergy and Clinical Immunology (2018)
A phase 2 study of azacitidine (5-AZA) with or without birinapant in subjects with higher risk myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML).
Authors: William Bruce Donnellan, Maria Diez-Campelo, Michael Heuser, Ellen K. Ritchie, Jeffrey Skolnik, Patricia Font, Rami S. Komrokji
Journal: Journal of Clinical Oncology (2016)

7060 Background: Inhibitor of Apoptosis Proteins (IAPs) are a family of molecules that are dysregulated in myeloid stem cell disorders and prevent programmed cell death. SMAC (second mitochondrial activator of caspase) is an endogenous antagonist of IAPs that counteracts their anti-apoptotic effect. Birinapant is a potent SMAC mimetic and in a phase Ib study of patients with MDS it demonstrated an acceptable safety profile and early signs of clinical activity. Methods: This was a multicenter, randomized, double-blind, placebo-controlled study of 5-AZA with or without birinapant in subjects with hypomethylating agent (HMA) naïve MDS and CMML. Eligible patients initially included de novo IPSS INT-2/high risk MDS or INT-1 risk with > / = 5% bone marrow blasts. The protocol was later amended to include secondary MDS, patients with low blast counts but high risk cytogenetics and patients with AML with low blast counts (20-30%). The primary objective was to compare response rate (RR = CR + PR) between the two arms. Adverse event profiling was a secondary objective. Patients were treated with 5-AZA 75 mg/m2/d IV on d 1-7 or 1-5, 8, 9 in 28 d cycles. Birinapant 13 mg/m2/d or placebo was administered IV twice weekly for 3 of 4 weeks (d 1, 4, 8, 11, 15, and 18). Results: The study was terminated early when a pre-planned interim analysis showed no difference in the response rate between the two arms. For evaluable patients the best overall response was 31.8% for placebo and 29.4% for birinapant (p = 0.96). Serious treatment-emergent adverse events (AEs) were higher in the birinapant arm than placebo arm (61.4% vs. 40.8%). Additionally, more patients had a treatment-emergent fatal AE in the birinapant arm (8.8% vs. 0%). Specific grade 3 or higher AEs that were increased in the birinapant arm included febrile neutropenia (34.4% vs. 10.3%), infections (28.1% vs. 13.8%), and thrombocytopenia (25% vs. 20.7%). Conclusions: In this phase 2, randomized, double-blind, placebo-controlled trial, the RR of birinapant plus 5-AZA was not superior to 5-AZA alone. Additionally, the AE and SAE rate was higher in the birinapant arm as compared to the placebo arm. Clinical trial information: NCT02147873.
Immediate retrieval of a maldeployed lumen-apposing metal stent from a walled-off cavity
Authors: Nabeel Azeem, Martin Freeman, Stuart Amateau
Journal: Endoscopy (2018)

A 46-year-old woman presented with a large walled-off collection, likely related to a prior episode of pancreatitis. Percutaneous drainage had been attempted at an outside institution, but the collection recurred. She was transferred urgently to our hospital in multiorgan failure with sepsis and abdominal pain.
Review: In primary care, CRP testing, shared decision making, and procalcitonin reduce antibiotic prescribing for ARI
Authors: Timothy S. Carey, Alan Kinlaw
Journal: Annals of Internal Medicine (2018)

Source Citation Tonkin-Crine SK, Tan PS, van Hecke O, et al. Clinician-targeted interventions to influence antibiotic prescribing behaviour for acute respiratory infections in primary care: an overview of systematic reviews. Cochrane Database Syst Rev. 2017;9:CD012252. 28881002
Treatment of adult chronic indeterminate Chagas disease with benznidazole and three E1224 dosing regimens: a proof-of-concept, randomised, placebo-controlled trial
Authors: Faustino Torrico, Joaquim Gascon, Lourdes Ortiz, Cristina Alonso-Vega, María-Jesús Pinazo, Alejandro Schijman, Igor C Almeida, Fabiana Alves, Nathalie Strub-Wourgaft, Isabela Ribeiro, Glaucia Santina, Bethania Blum, Erika Correia, Facundo Garcia-Bournisen, Michel Vaillant, Jimena Ramos Morales, Jimy Jose Pinto Rocha, Gimena Rojas Delgadillo, Helmut Ramon Magne Anzoleaga, Nilce Mendoza, Roxana Challapa Quechover, Maria Yurly Escobar Caballero, Daniel Franz Lozano Beltran, Albert Mendoza Zalabar, Lizeth Rojas Panozo, Alejandro Palacios Lopez, Dunia Torrico Terceros, Violeta Alejandra Fernandez Galvez, Letty Cardozo, Gabriela Cuellar, Rudy Nelson Vasco Arenas, Isabel Gonzales, Carlos Florencio Hoyos Delfin, Lineth Garcia, Rudy Parrado, Anabelle de la Barra, Nair Montano, Sandro Villarroel, Tomas Duffy, Margarita Bisio, Juan Carlos Ramirez, Fred Duncanson, Michael Everson, Antonia Daniels, Makoto Asada, Eugene Cox, David Wesche, Paul Matthias Diderichsen, Alexandre F Marques, Luis Izquierdo, Silvia Sanz Sender, Joan Carlos Reverter, Manuel Morales, Wladimiro Jimenez
Journal: The Lancet Infectious Diseases (2018)
Systemic <scp>IL</scp>‐2/anti‐<scp>IL</scp>‐2Ab complex combined with sublingual immunotherapy suppresses experimental food allergy in mice through induction of mucosal regulatory T cells
Authors: P. L. Smaldini, F. Trejo, J. L. Cohen, E. Piaggio, G. H. Docena
Journal: Allergy (2018)

Abstract Background Therapeutic tolerance restoration has been proven to modify food allergy in patients and animal models and although sublingual immunotherapy ( SLIT ) has showed promise, combined therapy may be necessary to achieve a strong and long‐term tolerance. Aims In this work, we combined SLIT with systemic administration of IL ‐2 associated with an anti‐ IL ‐2 monoclonal antibody ( IL ‐2/anti‐ IL ‐2Ab complex or IL ‐2C) to reverse the IgE‐mediated experimental allergy. Materials and Methods Balb/c mice were sensitized with cholera toxin and milk proteins and orally challenged with allergen to elicit hypersensitivity reactions. Then, allergic mice were treated with a sublingual administration of very low amounts of milk proteins combined with intraperitoneal injection of low doses of IL ‐2C. The animals were next re‐exposed to allergens and mucosal as well as systemic immunological parameters were assessed in vivo and in vitro . Results The treatment reduced serum specific IgE, IL ‐5 secretion by spleen cells and increased IL ‐10 and TGF ‐β in the lamina propria of buccal and duodenal mucosa. We found an augmented frequency of IL ‐10‐secreting CD 4 + CD 25 + Foxp3 + regulatory T cells (Treg) in the submaxilar lymph nodes and buccal lamina propria. Tregs were sorted, characterized and adoptively transferred to naïve mice, which were subsequently sensitized. No allergy was experienced in these mice and we encouragingly discovered a faster and more efficient tolerance induction with the combined therapy compared with SLIT . Conclusion The combination of two therapeutic strategies rendered Treg‐mediated tolerance more efficient compared to individual treatments and reversed the established IgE‐mediated food allergy. This approach highlights the ability of IL ‐2C to expand Tregs, and it may represent a promising disease‐modifying therapy for managing food allergy.
Cardiopulmonary hemodynamics and C-reactive protein as prognostic indicators in compensated and decompensated cirrhosis
Authors: Laura Turco, Guadalupe Garcia-Tsao, Ilenia Magnani, Marcello Bianchini, Martina Costetti, Cristian Caporali, Stefano Colopi, Emilio Simonini, Nicola De Maria, Federico Banchelli, Rosario Rossi, Erica Villa, Filippo Schepis
Journal: Journal of Hepatology (2018)
Increased Local IgE Production in Allergic Rhinitis (AR) During Rhinovirus (RV) Infection
Authors: DeVon C. Preston, Ahmed B. Hamed, Alexander J. Schuyler, John W. Steinke, Thomas A.E. Platts-Mills, Peter W. Heymann, Monica G. Lawrence, Larry Borish
Journal: Journal of Allergy and Clinical Immunology (2018)
Successful Engraftment of Donor Umbilical Cord Blood (UCB) Cells after Co-Transplantation of Nicord® (Ex Vivo Expanded UCB Progenitor Cells with Nicotinamide) and a Second Unmanipulated Cord Blood Unit after Myeloablative Chemotherapy in Pediatric Patients with Severe Sickle Cell Disease
Authors: Suhag H Parikh, Joel Brochstein, Paul L. Martin, Mitchell E. Horwitz, Einat Galamidi, Iddo Peleg, Uri Goshen, Aurelie Schwarzbach, David A. Snyder, Tony Peled, Joanne Kurtzberg
Journal: Blood (2016)
Glucagon-like peptide 1 signaling inhibits allergen-induced lung IL-33 release and reduces group 2 innate lymphoid cell cytokine production in vivo
Authors: Shinji Toki, Kasia Goleniewska, Sara Reiss, Jian Zhang, Melissa H. Bloodworth, Matthew T. Stier, Weisong Zhou, Dawn C. Newcomb, Lorraine B. Ware, Gregg D. Stanwood, Aurelio Galli, Kelli L. Boyd, Kevin D. Niswender, R. Stokes Peebles
Journal: Journal of Allergy and Clinical Immunology (2018)
Dentate network activity is necessary for spatial working memory by supporting CA3 sharp-wave ripple generation and prospective firing of CA3 neurons
Authors: Takuya Sasaki, Verónica C. Piatti, Ernie Hwaun, Siavash Ahmadi, John E. Lisman, Stefan Leutgeb, Jill K. Leutgeb
Journal: Nature Neuroscience (2018)
Patients with melanoma treated with an anti-PD-1 antibody beyond RECIST progression: a US Food and Drug Administration pooled analysis
Authors: Julia A Beaver, Maitreyee Hazarika, Flora Mulkey, Sirisha Mushti, Huanyu Chen, Kun He, Rajeshwari Sridhara, Kirsten B Goldberg, Meredith K Chuk, Dow-Chung Chi, Jennie Chang, Amy Barone, Sanjeeve Balasubramaniam, Gideon M Blumenthal, Patricia Keegan, Richard Pazdur, Marc R Theoret
Journal: The Lancet Oncology (2018)
Fluid Balance Is Associated with Clinical Outcomes and Extravascular Lung Water in Children with Acute Asthma Exacerbation
Authors: David B. Kantor, Eliotte L. Hirshberg, Molly C. McDonald, John Griffin, Tess Buccigrosso, Nicole Stenquist, Craig D. Smallwood, Kyle A. Nelson, David Zurakowski, Wanda Phipatanakul, Joel N. Hirschhorn
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

The effects of fluid administration during acute asthma exacerbation are likely unique in this patient population: highly negative inspiratory intrapleural pressure resulting from increased airway resistance may interact with excess fluid administration to favor the accumulation of extravascular lung water, leading to worse clinical outcomes.
Usefulness of asthma predictive index in ascertaining asthma status of children using medical records: An explorative study
Authors: C.‐I. Wi, E. A. Krusemark, G. Voge, S. Sohn, H. Liu, E. Ryu, M. A. Park, J. A. Castro‐Rodriguez, Y. J. Juhn
Journal: Allergy (2018)

Abstract Background Frequent wheezing in original asthma predictive index (API) was defined by parental report of recurrent wheezing within 1 year during the first 3 years of life. The nature of frequent wheezing in children, particularly aged over 3 years, has not been studied. We aimed to assess the frequency and interval of wheezing to define frequent wheezing in ascertaining asthma for children using medical records. Methods Among children who participated in a previous study (n = 427), all wheezing episodes documented in medical records were collected for children who had ≥2 wheezing episodes PLUS met one major criterion or two minor criteria of API. We compared the distribution of known risk factors for asthma between subjects having two consecutive wheezing episodes with shorter interval (≤1 year) compared to those with longer interval (1 to 3 years). Results A total of 62 children met API at median age of 2.3 years. During follow‐up period (median age: 11.3 years), a total of 198 wheezing episodes were observed. 81% of wheezing intervals were within 3 years from the earlier wheezing episode, including 60% within 1 year. Children who met API based on 1‐year interval (n = 40) vs 1‐ to 3‐year interval (n = 13) appeared to be similar in regard to the known risk factors for asthma. Conclusions Our exploratory study finding suggests that children who had frequent wheezing episodes with longer interval (&lt;3 years) need to be considered to be determined as asthma cases when API is applied to retrospective medical records. Prospective studies with a larger sample size need to replicate this finding.
First-Time Monitoring Of Simultaneous Effects Of Hypergravity On Heart And Lung By Electrical Impedance Tomography
Authors: João Batista Borges, Göran Hedenstierna, J. S. Bergman, C. Dussault, M. B. P. Amato, S. Montmerle-Borgdorff
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

First-Time Monitoring Of Simultaneous Effects Of Hypergravity On Heart And Lung By Electrical Impedance Tomography
RAGE binds preamyloid IAPP intermediates and mediates pancreatic β cell proteotoxicity
Authors: Andisheh Abedini, Ping Cao, Annette Plesner, Jinghua Zhang, Meilun He, Julia Derk, Sachi A. Patil, Rosa Rosario, Jacqueline Lonier, Fei Song, Hyunwook Koh, Huilin Li, Daniel P. Raleigh, Ann Marie Schmidt
Journal: Journal of Clinical Investigation (2018)

Islet amyloidosis is characterized by the aberrant accumulation of islet amyloid polypeptide (IAPP) in pancreatic islets, resulting in β cell toxicity, which exacerbates type 2 diabetes and islet transplant failure. It is not fully clear how IAPP induces cellular stress or how IAPP-induced toxicity can be prevented or treated. We recently defined the properties of toxic IAPP species. Here, we have identified a receptor-mediated mechanism of islet amyloidosis-induced proteotoxicity. In human diabetic pancreas and in cellular and mouse models of islet amyloidosis, increased expression of the receptor for advanced glycation endproducts (RAGE) correlated with human IAPP-induced (h-IAPP-induced) β cell and islet inflammation, toxicity, and apoptosis. RAGE selectively bound toxic intermediates, but not nontoxic forms of h-IAPP, including amyloid fibrils. The isolated extracellular ligand-binding domains of soluble RAGE (sRAGE) blocked both h-IAPP toxicity and amyloid formation. Inhibition of the interaction between h-IAPP and RAGE by sRAGE, RAGE-blocking antibodies, or genetic RAGE deletion protected pancreatic islets, β cells, and smooth muscle cells from h-IAPP-induced inflammation and metabolic dysfunction. sRAGE-treated h-IAPP Tg mice were protected from amyloid deposition, loss of β cell area, β cell inflammation, stress, apoptosis, and glucose intolerance. These findings establish RAGE as a mediator of IAPP-induced toxicity and suggest that targeting the IAPP/RAGE axis is a potential strategy to mitigate this source of β cell dysfunction in metabolic disease.
Black Phosphorus and its Biomedical Applications
Authors: Jane Ru Choi, Kar Wey Yong, Jean Yu Choi, Azadeh Nilghaz, Yang Lin, Jie Xu, Xiaonan Lu
Journal: Theranostics (2018)

Black phosphorus (BP), also known as phosphorene, has attracted recent scientific attention since its first successful exfoliation in 2014 owing to its unique structure and properties.In particular, its exceptional attributes, such as the excellent optical and mechanical properties, electrical conductivity and electron-transfer capacity, contribute to its increasing demand as an alternative to graphene-based materials in biomedical applications.Although the outlook of this material seems promising, its practical applications are still highly challenging.In this review article, we discuss the unique properties of BP, which make it a potential platform for biomedical applications compared to other 2D materials, including graphene, molybdenum disulphide (MoS2), tungsten diselenide (WSe2) and hexagonal boron nitride (h-BN).We then introduce various synthesis methods of BP and review its latest progress in biomedical applications, such as biosensing, drug delivery, photoacoustic imaging and cancer therapies (i.e., photothermal and photodynamic therapies).Lastly, the existing challenges and future perspective of BP in biomedical applications are briefly discussed.
Airway epithelial cells enhances tissue plasminogen activator by short chain fatty acids via G protein coupled receptor 41 and 43
Authors: Yoshimasa Imoto, Atsushi Kato, Tetsuji Takabayashi, Masafumi Sakashita, James E. Norton, Lydia A. Suh, Roderick G. Carter, Ava R. Weibman, Kathryn E. Hulse, Whitney W. Stevens, Kathleen E. Harris, Anju T. Peters, Leslie C. Grammer, Bruce K. Tan, Kevin C. Welch, David B. Conley, Robert C. Kern, Shigeharu Fujieda, Robert P. Schleimer
Journal: Journal of Allergy and Clinical Immunology (2018)