tbuckley/cabot-search huggingface dataset:
Identification and Modulation of Microenvironment Is Crucial for Effective Mesenchymal Stromal Cell Therapy in Acute Lung Injury
Authors: Diana Islam, Yongbo Huang, Vito Fanelli, Luisa Delsedime, Sulong Wu, Julie Khang, Bing Han, Alice Grassi, Manshu Li, Yonghao Xu, Alice Luo, Jianfeng Wu, Xiaoqing Liu, Montey McKillop, Jeffery Medin, Haibo Qiu, Nanshan Zhong, Mingyao Liu, John Laffey, Yimin Li, Haibo Zhang
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Rationale: There are controversial reports on applications of mesenchymal stromal cells (MSCs) in patients with acute respiratory distress syndrome (ARDS). Objectives: We hypothesized that lung microenvironment was the main determinant of beneficial versus detrimental effects of MSCs during ARDS. Methods: Lung proteome was profiled in three models of injury induced by acid instillation and/or mechanical ventilation in mice. Human gene of glutathione peroxidase-1 was delivered before MSC administration; or MSCs carrying human gene of IL-10 or hepatocyte growth factor were administered after lung injury. An inhibitory cocktail against IL-6, fibronectin, and oxidative stress was used in in vitro studies using human small airway epithelial cells and human MSCs after exposure to plasma of patients with ARDS. Measurements and Main Results: Distinct proteomic profiles were observed in three lung injury models. Administration of MSCs protected lung from ventilator-induced injury, whereas it worsened acid-primed lung injuries associated with fibrotic development in lung environment that had high levels of IL-6 and fibronectin along with low antioxidant capacity. Correction of microenvironment with glutathione peroxidase-1, or treatment with MSCs carrying human gene of IL-10 or hepatocyte growth factor after acid-primed injury, reversed the detrimental effects of native MSCs. Proteomic profiles obtained in the mouse models were also similarly observed in human ARDS. Treatment with the inhibitory cocktail in samples of patients with ARDS retained protective effects of MSCs in small airway epithelial cells. Conclusions: MSCs can be beneficial or detrimental depending on microenvironment at the time of administration. Identification of potential beneficiaries seems to be crucial to guide MSC therapy in ARDS.
Squamous cell carcinoma keratinocytes isolated from patients with recessive dystrophic epidermolysis bullosa invade collagen-matrigel organotypic skin equivalents in an autonomous fashion
Authors: C. Pourreyron, K. Purdie, L. Bruckner-Tuderman, C. M. Proby, J. A. McGrath, I. M. Leigh, A. P. South
Journal: British Journal of Dermatology (2008)
Abstract 16231: Combining Mechanical Chest Compressions With a Percutaneous Left Ventricular Assist Device Improves Favorable Neurological Function After Cardiac Arrest in a Large Animal Catheterization Laboratory
Authors: Huu Tam Truong, Kapildeo Lotun, Nicole Smith, Prashant Rao, Renan Gianotto-Oliveira, Joseph M Rivera-Zotigh, Aaron Done, Siddhant Talwar, Thy Tran, Chiu-Hsieh Hsu, Karl B Kern
Journal: Circulation (2017)

Background: Cardiac arrest in the cardiac catheterization laboratory often fails to respond to resuscitation efforts until the culprit artery is successfully reperfused. While attempting to correct...
Sibling Recurrence Risk and Cross-aggregation of Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder
Authors: Meghan Miller, Erica D. Musser, Gregory S. Young, Brent Olson, Robert D. Steiner, Joel T. Nigg
Journal: JAMA Pediatrics (2018)

Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are believed to partially share genetic factors and biological influences. As the number of children with these diagnoses rises, so does the number of younger siblings at presumed risk for ADHD and ASD; reliable recurrence risk estimates within and across diagnoses may aid screening and early detection efforts and enhance understanding of potential shared causes.To examine within-diagnosis sibling recurrence risk and sibling cross-aggregation of ADHD and ASD among later-born siblings of children with either disorder.Using data extracted from medical records of 2 large health care systems in the United States, estimates of recurrence risk and cross-aggregation in later-born siblings of children with ADHD or ASD were compared with later-born siblings of children without these diagnoses. One data set included children seen between January 1, 1995, and December 31, 2013; the other included children born between January 1, 1998, and May 17, 2010. Participants included 15 175 later-born siblings of children with ADHD, ASD, and no known diagnosis. The study was conducted from October 2, 2017, to August 14, 2018.Diagnoses of ASD or ADHD in the later-born sibling, ascertained from medical records, were the primary outcomes of interest; moderators included sex, gestational age, and maternal age.A total of 15 175 later-born siblings were classified by familial risk status based on the older child's diagnostic status: ADHD risk (n = 730; male [51.92%]), ASD risk (n = 158; male [48.10%]), and no known risk (n = 14 287; male [50.73%]). Compared with later-born siblings of children without ADHD or ASD, later-born siblings of children with ASD were more likely to be diagnosed with ASD (odds ratio [OR], 30.38; 95% CI, 17.73-52.06) or ADHD in the absence of ASD (OR, 3.70; 95% CI, 1.67-8.21). Compared with later-born siblings of children without a diagnosis, later-born siblings of children with ADHD were more likely to be diagnosed with ADHD (OR, 13.05; 95% CI, 9.86-17.27) or ASD in the absence of ADHD (OR, 4.35; 95% CI, 2.43-7.79).Later-born siblings of children with ASD or ADHD appear to be at elevated risk for the same disorder, but also of being diagnosed with the other disorder. These findings provide further support for shared familial mechanisms underlying ASD and ADHD, which may be useful for genetic and prospective developmental studies. Later-born siblings of children with ADHD or ASD should be monitored for both conditions.
Cell‐Templated Silica Microparticles with Supported Lipid Bilayers as Artificial Antigen‐Presenting Cells for T Cell Activation
Authors: Brynn R. Olden, Caleb R. Perez, Ashley L. Wilson, Ian I. Cardle, Yu‐Shen Lin, Bryan Kaehr, Joshua A. Gustafson, Michael C. Jensen, Suzie H. Pun
Journal: Advanced Healthcare Materials (2018)

Abstract Biomaterial properties that modulate T cell activation, growth, and differentiation are of significant interest in the field of cellular immunotherapy manufacturing. In this work, a new platform technology that allows for the modulation of various activation particle design parameters important for polyclonal T cell activation is presented. Artificial antigen presenting cells (aAPCs) are successfully created using supported lipid bilayers on various cell‐templated silica microparticles with defined membrane fluidity and stimulating antibody density. This panel of aAPCs is used to probe the importance of activation particle shape, size, membrane fluidity, and stimulation antibody density on T cell outgrowth and differentiation. All aAPC formulations are able to stimulate T cell growth, and preferentially promote CD8 + T cell growth over CD4 + T cell growth when compared to commercially available pendant antibody‐conjugated particles. T cells cultured with HeLa‐ and red blood cell–templated aAPCs have a less‐differentiated and less‐exhausted phenotype than those cultured with spherical aAPCs with matched membrane coatings when cultured for 14 days. These results support continued exploration of silica‐supported lipid bilayers as an aAPC platform.
ADAM9: A Damaging Player in Chronic Obstructive Pulmonary Disease
Authors: Derek W. Russell, Amit Gaggar
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

A Damaging Player in Chronic Obstructive Pulmonary DiseaseThe inflammatory smoking-associated condition chronic obstructive pulmonary disease (COPD) can be broadly conceived as simple alveolar enlargement coupled with airway inflammation (1), which together culminate in airflow obstruction (2).However, underlying these qualitative changes in the lungs of COPD sufferers is a host of complex, interdependent processes combined in a sometimes paradoxical fashion, all of which conspire to increase airway resistance.The emphysema seen in COPD is a wellknown example of excessive extracellular matrix degradation leading to proteolytic tissue loss (3).In part because of this loss of matrix anchoring (4), and in part because of reduced resiliency (and a tendency toward apoptosis) of the alveolar pneumocytes ( 5), the cellular units that overlie these septae also are lost in COPD, causing emphysema.However, it is now established that COPD is also associated with excesses of abnormal extracellular matrix deposition in the pulmonary parenchyma (6), which, probably along with other mechanisms (7, 8), culminates in dramatic pruning of the small airways.The third major pathophysiologic derangement of COPD pertains to the larger airways, which undergo hypertrophic and metaplastic remodeling, causing increased mucus production and large-airway inflammation, that is, chronic bronchitis.These complex and seemingly disparate disease characteristics, as well as a predisposition to local and systemic inflammation, generally carry forward in patients, albeit at a slower rate, even if smoking cessation is achieved once COPD has become established (9, 10).In this issue of the Journal, Wang and colleagues (pp.1500-1518) describe a mediator, ADAM9 (a disintegrin and metalloprotease domain-9), that was previously linked to acute lung injury (11) and appears to be upregulated in inflammatory cells in response to cigarette smoke (CS) injury ( 12).They relate the activity of this enzyme to a surprising number of the diverse pathologies seen in COPD . . .almost one for each of the seven functional domains on this pleiotropic enzyme.This suggests a potential proximity of ADAM9 to the pathogenetic epicenter of COPD, and thus implies that ADAM9 has considerable potential as a therapeutic target in these wide-ranging dysfunctions.The authors used a combination of ADAM9 2/2 CS-exposed animals, enzymologic studies, and studies of tissue, cells, and clinical samples from subjects with and without various degrees of COPD and/or CS exposure to demonstrate these findings in vivo and in vitro.The findings include multiple distinct effects of ADAM9 on all three of the key pathophysiologic mechanisms of COPD mentioned above (Figure 1): 1) emphysema (direct elastolysis, excessive alveolar pneumocyte apoptosis, and increased accumulation of leukocytes, especially alveolar macrophages); 2) small-airways fibrosis (which may be due to both the
Post Allogeneic Stem Cell Transplant (SCT) Cyclophosphamide Improves Progression Free Survival (PFS) in Pts with AML/MDS Treated with CTLA-4 or PD-1 Blockade Prior to SCT
Authors: Betul Oran, Guillermo Garcia-Manero, Rima M. Saliba, Gheath Alatrash, Elias J. Jabbour, Uday Popat, Farhad Ravandi, Tapan M. Kadia, Jorge E. Cortes, Amin M. Alousi, Marina Y. Konopleva, Courtney D. DiNardo, Katy Rezvani, Mansour Alfayez, Elizabeth J. Shpall, Padmanee Sharma, Richard E Champlin, Hagop M. Kantarjian, Naval G. Daver
Journal: Blood (2018)
Listen to Your Patient
Authors: Nadia R. Sutton, Brahmajee K. Nallamothu
Journal: JAMA Network Open (2018)

Yuan Lu, ScD; Haibo Zhang, MD; Yongfei Wang, MS; Tianna Zhou, BS; John Welsh, BA; Jiamin Liu, MD; Wenchi Guan, MD; Jing Li, MD; Xi Li, MD; Xin Zheng, MD; John A. Spertus, MD, MPH; Frederick A. Masoudi, MD, MSPH; Harlan M. Krumholz, MD, SM; Lixin Jiang, MD, PhD
Global long terminal repeat activation participates in establishing the unique gene expression programme of classical Hodgkin lymphoma
Authors: Benjamin Edginton-White, Pierre Cauchy, Salam A. Assi, Sylvia Hartmann, Arthur G. Riggs, Stephan Mathas, Peter N. Cockerill, Constanze Bonifer
Journal: Leukemia (2018)

Long terminal repeat (LTR) elements are wide-spread in the human genome and have the potential to act as promoters and enhancers. Their expression is therefore under tight epigenetic control. We previously reported in classical Hodgkin Lymphoma (cHL) that a member of the THE1B class of LTR elements acted as a promoter for the proto-oncogene and growth factor receptor gene CSF1R and that expression of this gene is required for cHL tumour survival. However, to which extent and how such elements participate in globally shaping the unique cHL gene expression programme is unknown. To address this question we mapped the genome-wide activation of THE1-LTRs in cHL cells using a targeted next generation sequencing approach (RACE-Seq). Integration of these data with global gene expression data from cHL and control B cell lines showed a unique pattern of LTR activation impacting on gene expression, including genes associated with the cHL phenotype. We also show that global LTR activation is induced by strong inflammatory stimuli. Together these results demonstrate that LTR activation provides an additional layer of gene deregulation in classical Hodgkin lymphoma and highlight the potential impact of genome-wide LTR activation in other inflammatory diseases.
SP0063 Win session: about diagnosis and classification of spondyloarthritis
Authors: V. Navarro Compán
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> In patients with axial spondyloarthritis (axSpA) an early diagnosis is becoming progressively more relevant. Nowadays, several therapies have shown to be efficacious to control disease symptoms and signs and they are even more useful if administered in early stages of the disease. However, the aim of an early diagnosis is not easy to achieve. Similar to the majority of rheumatic diseases, axSpA is heterogeneous in its presentation, course, and outcome, and does not have a single clinical, laboratory, pathological, or radiological feature to serve as a gold standard in support of diagnosis. With the new therapies available, many research studies are focusing on how to make an early diagnosis of axSpA. Additionally, some confusion remains about differences between classification and diagnosis of axSpA. In clinical practice, in the absence of diagnostic criteria, the classification criteria are often used to assist in the diagnostic process of a disease. Based on this, there is an ongoing debate about whether or not the current classification criteria should be revised. During this session, the new insights on diagnosis and classification in axSpA will be highlited. <h3>Disclosure of Interest</h3> None declared
Hepatitis D prevalence: problems with extrapolation to global population estimates
Authors: Alexander J Stockdale, Benno Kreuels, Marc R Y Henrion, Emanuele Giorgi, Irene Kyomuhangi, Anna Maria Geretti
Journal: Gut (2018)

We read the meta-analysis of global hepatitis D prevalence by Chen et al and have some serious concerns relating to the proposed epidemiological estimates.1 

Seroprevalence of hepatitis delta virus (HDV) was not adequately defined. In the methods, hepatitis delta antibody (anti-HDV), HDV RNA and HDV antigen (HDAg) were described as markers of HDV infection. In Supplementary Table S8, it is evident that total, IgG and IgM anti-HDV and HDAg were variably used to define HDV infection. HDAg is a transient marker of HDV infection, whereas IgM expression is inconsistently associated with both acute and chronic infection; neither are suitable epidemiological markers of chronic HDV infection.2 

A total of 50 cohorts were used to inform the primary outcome, global HDV seroprevalence in the general population; of these, 30 were conducted in the last 20 years. The authors estimated …
Tackling HIV by empowering adolescent girls and young women: a multisectoral, government led campaign in South Africa
Authors: Hasina Subedar, Sarah Barnett, Tsakani Chaka, Sibongile Dladla, Ellen Hagerman, Sarah Jenkins, Gertrude Matshimane, Kerry Mangold, Busi Msimanga, Ruth Pooe, Lebogang Schultz, Yogan Pillay
Journal: BMJ (2018)

<b>Hasina Subedar and colleagues</b> describe the intersectoral collaboration enabling She Conquers, a three year national campaign rolled out across South Africa, to tackle the multiple drivers of the high rates of HIV infection among adolescent girls and young women
Feasibility and Safety of Intracoronary Imaging for Diagnosing Spontaneous Coronary Artery Dissection
Authors: Fernando Macaya, Carlos H. Salazar, María J. Pérez-Vizcayno, Pablo Salinas, Pilar Jiménez-Quevedo, Luis Nombela-Franco, María del Trigo, Iván Núñez-Gil, Antonio Fernández-Ortiz, Carlos Macaya, Javier Escaned, Nieves Gonzalo
Journal: JACC. Cardiovascular imaging (2018)
Activating Mutations in <i>Pik3ca</i> Contribute to Anal Carcinogenesis in the Presence or Absence of HPV-16 Oncogenes
Authors: Myeong-Kyun Shin, Susan Payne, Andrea Bilger, Kristina A. Matkowskyj, Evie Carchman, Dominique S. Meyer, Mohamed Bentires-Alj, Dustin A. Deming, Paul F. Lambert
Journal: Clinical Cancer Research (2018)

Over 95% of human anal cancers are etiologically associated with high-risk HPVs, with HPV type 16 (HPV16) the genotype most commonly found. Activating mutations in the catalytic subunit of Phosphatidylinositol (3,4,5)-trisphosphate kinase (PI3K), encoded by the Pik3ca gene, are detected in approximately 20% of human anal cancers.Experimental Design: We asked if common activating mutations in Pik3ca contribute to anal carcinogenesis using an established mouse model for anal carcinogenesis in which mice are topically treated with the chemical carcinogen 7,12-Dimethylbenz(a)anthracene (DMBA). Mice expressing in their anal epithelium one of two activating mutations in Pik3ca genes, Pik3caH1047R or Pik3caE545K , were monitored for anal carcinogenesis in the presence or absence of transgenes expressing the HPV16 E6 and E7 oncogenes.Both mutant forms of Pik3ca increased susceptibility to anal carcinogenesis in the absence of HPV16 oncogenes, and cooperated with HPV16 oncogenes to induce the highest level and earliest onset of anal cancers. The combination of HPV16 oncogenes and Pik3ca mutations led to anal cancers even in the absence of treatment with DMBA. We further observed that the investigational mTOR1/2 dual inhibitor, TAK-228, significantly reduced the size of anal cancer-derived tumor spheroids in vitro and reduced the growth rates of anal cancer-derived tumor grafts in vivo.These data demonstrate that activating mutations in Pik3ca drive anal carcinogenesis together with HPV16 oncogenes, and that the PI3K/mTOR pathway is a relevant target for therapeutic intervention.
Tumor-Induced Osteomalacia
Authors: Jill E Vollbrecht, D Sudhaker Rao
Journal: New England Journal of Medicine (2008)

An 87-year-old woman was referred to the endocrinology clinic in 1979 for hypophosphatemia (serum phosphate level consistently <1.5 mg per deciliter [0.48 mmol per liter]) causing cramps and myalgia; tumor-induced osteomalacia was diagnosed. A radiograph of the hand showed a lytic lesion at the third metacarpal bone (Panel A, arrow). Results of a complete skeletal survey were negative. The patient declined biopsy and tumor resection but agreed to receive therapy with phosphate and calcitriol; there was some improvement in her serum phosphate levels, although normalization was never achieved. Although periodically lost to follow-up, the patient remained otherwise healthy, with no . . .
Trends in Medicare Utilization by Dermatologists, 2012-2015
Authors: Jason Ya, Harib H. Ezaldein, Jeffrey F. Scott
Journal: JAMA Dermatology (2018)

Medicare represents the second largest component of national health expenditures, and dermatologists receive a disproportionate percentage of Medicare payments. Analyzing trends in Medicare utilization by dermatologists informs optimal Medicare usage for both patients and physicians.
Abstract 117: Gender Differences in Outcome After Out-of-Hospital Cardiac Arrest: Analysis of the LINC Trial
Authors: Erik Lindgren, Ollie Östlund, Sten Rubertsson
Journal: Circulation (2014)

BACKGROUND: Despite several factors associated with poor outcome after out-of-hospital cardiac arrests (OHCA), female gender is considered to be an independent predictor of survival after OHCA. Nev...
Direct reprogramming of fibroblasts into antigen-presenting dendritic cells
Authors: Fábio F. Rosa, Cristiana F. Pires, Ilia Kurochkin, Alexandra G. Ferreira, Andreia M. Gomes, Luís G. Palma, Kritika Shaiv, Laura Solanas, Cláudia Azenha, Dmitri Papatsenko, Oliver Schulz, Caetano Reis e Sousa, Carlos-Filipe Pereira
Journal: Science Immunology (2018)

Ectopic expression of transcription factors PU.1, IRF8, and BATF3 reprograms fibroblasts to dendritic cells.
Phase 1b trial of an ibrutinib-based combination therapy in recurrent/refractory CNS lymphoma
Authors: Christian Grommes, Sarah S. Tang, Julia Wolfe, Thomas J. Kaley, Mariza Daras, Elena I. Pentsova, Anna F. Piotrowski, Jacqueline Stone, Andrew Lin, Craig P. Nolan, Malbora Manne, Paolo Codega, Carl Campos, Agnes Viale, Alissa A. Thomas, Michael F. Berger, Vaios Hatzoglou, Anne S. Reiner, Katherine S. Panageas, Lisa M. DeAngelis, Ingo K. Mellinghoff
Journal: Blood (2018)
<i>Notes from the Field:</i> Follow-Up on 11 Infants Born to Women with Evidence of Zika Virus Infection During Pregnancy — Los Angeles County, 2016
Authors: Curtis Croker, Amy Marutani, Marita Santos, Susan Hathaway, Bessie Hwang
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

During 2016, 11 infants were born to women in Los Angeles County who met the Council of State and Territorial Epidemiologists case definition for confirmed (four infants) or probable (seven) Zika virus infection.
Abstract 14254: Right Ventricular Reverse Remodeling and Improved Systolic Function After Upfront Combination Therapy With Ambrisentan and Tadalafil in the Treatment of Scleroderma-Associated Pulmonary Arterial Hypertension
Authors: Chiara Pisanello, Roham Zamanian, Rachel Damico, Todd Kolb, Ryan Tedford, Takahiro Sato, Celia Corona-Villalobos, Stefan Zimmerman, Omar Minai, Fernando Torres, Kelly Chin, Reda Girgis, Stephen Mathai, Paul Hassoun
Journal: Circulation (2015)

Introduction: We assessed the effects of upfront, combination therapy with a phosphodiesterase inhibitor (tadalafil) and endothelin receptor antagonist (ambrisentan) on changes in size and function of the right ventricle (RV), in a prospective open label trial for treatment naïve scleroderma-associated pulmonary arterial hypertension (SSc-PAH) patients. Methods: In this multicentric open-label trial, 24 treatment naïve SSc-PAH patients received tadalafil (40 mg daily) and ambrisentan (10 mg daily) daily for 36 weeks. Two-dimensional convenctional echocardiography (2D-E) with speckle tracking (ST) study and cardiac magnetic resonance imaging (cMRI) were performed at baseline and 36 weeks. Results: Treatment with upfront combination therapy resulted in RV reverse remodeling, defined as a relative decrease in RV end-systolic area of at least 15% at echocardiographic evaluation at 36 weeks. cMRI at follow up showed a reduction in RV end-systolic volume 82.1 (IQR 65.6-97.7) vs 55.8 (IQR 49.4-79.2), p= 0.001, RV mass index 17.2 (IQR 13.4-27.3) vs 15.4 (IQR 11.7-20.3), p= 0.02, and ventricular mass index (VMI= RV/LV mass index) 0.32 (IQR 0.29-0.45) vs 0.27 (IQR 0.23-0.33), p= 0.02. After 36 weeks of therapy, an improvement in RV function was observed by tricuspid annular plane systolic excursion (TAPSE; 1.7 ± 0.5 vs 2.2 ± 0.5, p=0.02) and RV fractional area (FAC; 31.5 ± 12.3 vs 42.8 ± 9.7, p=0.002) changes. Tricuspid annular S’, calculated using ST, was significantly improved (7 ± 2.3 vs 8.9 ± 2.4, p=0.01), while longitudinal strain (-16 ± 6.4 vs -19 ± 4.9, p=0.09) and systolic strain rate (-0.8 ± 0.2 vs -0.9 ± 0.2, p=0.08) showed a trend toward improvement. Conclusion: Upfront combination therapy in treatment naïve SSc-PAH patients induces both reverse remodeling of the RV, with reduction in systolic RV volume, RV mass index and VMI, and significant increase in RV systolic function as shown by the increase in TAPSE, FAC and S’.