tbuckley/cabot-search huggingface dataset:
Treatment of keloids with a single dose of low-energy superficial X-ray radiation to prevent recurrence after surgical excision: An in vitro and in vivo study
Authors: Yuna Son, Ernest Owen Nicandro Phillips, Kristin Magrini Price, Laurence Zalmon Rosenberg, Branko Stefanovic, Christopher Michael Wolfe, Tarek Samir Shaath, Amit Om, George Franklin Cohen, Akash Gunjan
Journal: Journal of the American Academy of Dermatology (2020)
HER2-LAMP vaccines effectively traffic to endolysosomal compartments and generate enhanced polyfunctional T cell responses that induce complete tumor regression
Authors: Alan Chen Chen, Renhuan Xu, Tao Wang, Junping Wei, Xiao-Yi Yang, Cong-Xiao Liu, Gangjun Lei, Herbert Kim Lyerly, Teri Heiland, Zachary Conrad Hartman
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background The advent of immune checkpoint blockade antibodies has demonstrated that effective mobilization of T cell responses can cause tumor regression of metastatic cancers, although these responses are heterogeneous and restricted to certain histologic types of cancer. To enhance these responses, there has been renewed emphasis in developing effective cancer-specific vaccines to stimulate and direct T cell immunity to important oncologic targets, such as the oncogene human epidermal growth factor receptor 2 (HER2), expressed in ~20% of breast cancers (BCs). Methods In our study, we explored the use of alternative antigen trafficking through use of a lysosome-associated membrane protein 1 (LAMP) domain to enhance vaccine efficacy against HER2 and other model antigens in both in vitro and in vivo studies. Results We found that inclusion of this domain in plasmid vaccines effectively trafficked antigens to endolysosomal compartments, resulting in enhanced major histocompatibility complex (MHC) class I and II presentation. Additionally, this augmented the expansion/activation of antigen-specific CD4+ and CD8+ T cells and also led to elevated levels of antigen-specific polyfunctional CD8+ T cells. Significantly, vaccination with HER2-LAMP produced tumor regression in ~30% of vaccinated mice with established tumors in an endogenous model of metastatic HER2+ BC, compared with 0% of HER2-WT vaccinated mice. This therapeutic benefit is associated with enhanced tumor infiltration of activated CD4+ and CD8+ T cells. Conclusions These data demonstrate the potential of using LAMP-based endolysosomal trafficking as a means to augment the generation of polyfunctional, antigen-specific T cells in order to improve antitumor therapeutic responses using cancer antigen vaccines.
Bortezomib/Cyclophosphamide/Dexamethasone Versus Lenalidomide/Cyclophosphamide/Dexamethasone in Multiple Myeloma Patients at First Relapse: Final Results of a Phase III Study
Authors: Vittorio Montefusco, Alessandro Corso, Monica Galli, Elena Tagliabue, Sara Pezzatti, Francesca Patriarca, Filippo Gherlinzoni, Renato Zambello, Simona Sammassimo, Magda Marcatti, Andrea Nozza, Claudia Crippa, Anna Maria Cafro, Luca Baldini, Paolo Corradini
Journal: Blood (2017)
Improving the diagnostic efficiency of primary immunodeficiencies with targeted next-generation sequencing
Authors: Mathieu Fusaro, Jérémie Rosain, Virginie Grandin, Nathalie Lambert, Sylvain Hanein, Cécile Fourrage, Nicholas Renaud, Marine Gil, Samuel Chevalier, Wadih Abou Chahla, Brigitte Bader-Meunier, Vincent Barlogis, Stéphane Blanche, David Boutboul, Martin Castelle, Thibault Comont, Jean-Sébastien Diana, Claire Fieschi, Lionel Galicier, Olivier Hermine, Alain Lefèvre-Utile, Marion Malphettes, Etienne Merlin, Eric Oksenhendler, Marlène Pasquet, Felipe Suarez, Isabelle André, Vivien Béziat, Geneviève De Saint Basile, Jean-Pierre De Villartay, Sven Kracker, Chantal Lagresle-Peyrou, Sylvain Latour, Frédéric Rieux-Laucat, Nizar Mahlaoui, Christine Bole, Patrick Nitschke, Elisabeth Hulier-Ammar, Alain Fischer, Despina Moshous, Bénédicte Neven, Alexandre Alcais, Guillaume Vogt, Jacinta Bustamante, Capucine Picard
Journal: Journal of Allergy and Clinical Immunology (2020)
Abstract B25: Isolation and engraftment of circulating tumor cells into zebrafish embryos to predict tumor response of ovarian cancer patients
Authors: Charlotte Fieuws, Jeroen Vierstraete, Koen Van De Vijver, Hannelore Denys, Kathleen BM Claes
Journal: Clinical Cancer Research (2020)

Abstract Ovarian cancer is characterized by poor prognosis and high relapse rate, unfortunately accompanied with resistance to previously used therapy. Currently, resistance is defined by the time between treatment and progression of the disease. A better model to test resistance is to make patient-derived xenografts (PDX). We propose here the development of a PDX platform in zebrafish. This model allows testing of both previously used treatment and possible other treatment strategies. The fast readout of less than 15 days and the limited amount of material required (few 100s of cells) allow implementation in clinical practice. In a first phase, a correlation study will be performed to establish that zebrafish PDX models mimic the response of the patient to adjuvant chemotherapy by using primary tumor tissue. In the second phase of this project, circulating tumor cells will be isolated at different time points during treatment and follow-up. The objective of this part of the study is to isolate and cultivate CTCs for engraftment. For this we will apply a recently introduced size-based separation method (MetaCell®). The viable cells will undergo a short in vitro culture to expand and to get rid of remaining lymphocytes. Possible changes in mesenchymal-to-epithelial transition are picked up by single-cell sequencing (10xGenomics®) of the cells prior and post culturing. After culturing the CTCs are fluorescently labeled and engrafted into two-day-old zebrafish embryos. Tumors are formed the following day and treated with different treatment options for three executive days. Tumor proliferation and growth is observed in vivo through fluorescence microscopy. Post-mortem readouts are based on immunohistochemistry profiles. Resistance is defined by high proliferation rate (Ki-67) and mitotic index and low apoptosis rate (Caspase-3). Comparative morphology with primary tissue and CTC-PDX is evaluated by hematoxylin and eosin staining on FFPE-slices. This methodology may provide an opportunity for more personalized medicine in which treatment for OC may be guided by information from an individual’s zebrafish PDX response to therapy. Citation Format: Charlotte Fieuws, Jeroen Vierstraete, Koen Van De Vijver, Hannelore Denys, Kathleen BM Claes. Isolation and engraftment of circulating tumor cells into zebrafish embryos to predict tumor response of ovarian cancer patients [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr B25.
Toward Inclusion of Youths With Psychiatric Disorders in Brain-Body Research
Authors: Benjamin I. Goldstein, Alvi Islam, Melanie Naiberg
Journal: JAMA Pediatrics (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Neuropathological Features of Covid-19
Authors: Isaac H. Solomon, Erica Normandin, Shamik Bhattacharyya, Shibani S. Mukerji, Kiana Keller, Ahya S. Ali, Gordon Adams, Jason L. Hornick, Robert F. Padera, Pardis Sabeti
Journal: New England Journal of Medicine (2020)

Brain Autopsy Series in Patients with Covid-19 Eighteen brains of patients who died 0 to 32 days after the onset of symptoms of SARS-CoV-2 infection showed hypoxic–ischemic changes but no encephali...
THU0053 CONTRIBUTION OF DEFECTIVE NON-APOPTOTIC FAS SIGNALING TO IMMUNE DYSREGULATION IN AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME (ALPS)
Authors: J. Staniek, T. Kalina, G. Andrieux, M. Boerries, I. Janowska, M. Fuentes, M. Bakardjieva, J. Raabe, J. Neumann, J. Stuchly, V. Benes, R. Garcia, J. Garcia, P. Diez, A. Catala, B. Neven, O. Neth, P. Olbrich, R. Voll, L. Alsina, L. Allende, L. Gonzales-Granado, J. Thiel, N. Venhoff, R. Lorenzetti, S. Unger, M. Seidl, D. Mielenz, P. Schneider, S. Ehl, A. Rensing-Ehl, C. Smulski, M. Rizzi
Journal: Annals of the Rheumatic Diseases (2020)

Background: ALPS patients show impaired generation of humoral memory for T independent antigens whereas they generate memory for self-antigens due to impaired FAS-dependent removal of autoreactive germinal center B cells. It is known that FAS signaling via caspase activation results in cell apoptosis. However, FAS ligation may also initiate or modulate non-apoptotic signaling as shown for example by its ability to activate NF-κB. Recent data implicate a regulatory role of FAS in the modulation of mTOR signaling in ALPS double-negative T cells. Moreover, a recently described C194V FAS mutation disturbs its post-translational modification leading to impaired apoptosis induction while non-apoptotic signalling is still intact. Consequently, C194V FAS protects from the autoimmune phenotype in the murine ALPS system. This supports the view that FAS may prevent autoimmunity with other mechanisms than inducing apoptosis. Objectives: We hypothesize that FAS mutations impair this modulatory signaling, leading to hyper-activation of B cells. Therefore we aim to investigate non apoptotic FAS signaling in B cells derived from healthy individuals and ALPS patients. Methods: We studied resting and activated B cells in ALPS patients in presence or absence of FAS ligand by flow cytometry analysing relevant molecules to the CD40 signaling pathway. We used mass cytometry to perform functional phenotyping of B cells isolated from secondary lymphoid organs. Proteomic studies were performed to identify potential signaling circuits and RNA sequencing to study the consequences of FAS signaling on B cell fate. Results: In CD40L activated B cells, FAS signaling results in specific modulation of the mTOR signaling pathway. This modulation is absent in ALPS derived B cells. In line with these data germinal center B cells and plasmablast from secondary lymphoid organs of ALPS patients show hyperactive mTOR signaling pathway. Proteomic studies identify a circuit that links FAS to the phosphatase PTEN via DAXX and the deubiquitinase USP7. Conclusion: We describe a new role of FAS in the regulation of B cell activation. Defects in FAS signaling in ALPS contribute to dysregulation of the mTOR signaling pathway and disturbed B cell development. Disclosure of Interests: None declared
Obesity-Induced Cellular Senescence Drives Anxiety and Impairs Neurogenesis
Authors: Mikolaj Ogrodnik, Yi Zhu, Larissa G.P. Langhi, Tamar Tchkonia, Patrick Krüger, Edward Fielder, Stella Victorelli, Rifqha A. Ruswhandi, Nino Giorgadze, Tamar Pirtskhalava, Oleg Podgorni, Grigori Enikolopov, Kurt O. Johnson, Ming Xu, Christine Inman, Allyson K. Palmer, Marissa Schafer, Moritz Weigl, Yuji Ikeno, Terry C. Burns, João F. Passos, Thomas von Zglinicki, James L. Kirkland, Diana Jurk
Journal: Cell Metabolism (2019)

(Cell Metabolism 29, 1061–1077.e1–e8; May 7, 2019) In the original publication of this paper, Allyson K. Palmer, who contributed to the data analysis and provided some of the db/db animals, was not included in the original list of authors. All co-authors on the manuscript have approved this addition. This has since been corrected online. The authors apologize for the error. Obesity-Induced Cellular Senescence Drives Anxiety and Impairs NeurogenesisOgrodnik et al.Cell MetabolismJanuary 3, 2019In BriefObesity, a growing health problem in western societies, is associated with increased senescent cells and neuropsychiatric disorders, including anxiety and depression. Ogrodnik and colleagues found that clearance of senescent cells in obese mice alleviates anxiety. Our study provides proof-of-concept evidence that senolytics are a potential new therapeutic avenue for treating neuropsychiatric disorders. Full-Text PDF Open Access
Endoscopic filling with polyglycolic acid sheets and fibrin glue of persistent fistula after esophagectomy
Authors: Kousei Tashiro, Shinsuke Takeno, Fumiaki Kawano, Eiji Kitamura, Rouko Hamada, Makoto Ikenoue, Shun Munakata, Atsushi Nanashima, Kunihide Nakamura
Journal: Endoscopy (2020)

Background Treatment of anastomotic leakage in reconstruction after esophagectomy remains challenging. This report presents a new endoscopic filling method for persistent fistula after failure of conservative treatment of leakage caused by anastomotic insufficiency. Methods 10 of 14 patients, in whom post-esophagectomy leakage had failed to resolve after 2 weeks of conservative treatment, underwent endoscopic filling with polyglycolic acid (PGA) sheet and fibrin glue into the anastomotic leakage site, using a delivery tube and endoscopic catheter, respectively. Results Each patient underwent jejunostomy, to secure nutrition. The leakage was resolved in all 10 patients. The mean number of PGA – fibrin glue procedures was 1.7. The mean period from the first application to the resumption of oral intake was 31.6 days, from the final application it was 14.7 days. Conclusions The reported filling method offers a new endoscopic approach for persistent fistula after esophagectomy when conservative treatment of leakage has failed.
PARE0006 WORK PRODUCTIVITY LOSS IN PATIENTS WITH INFLAMMATORY ARTHRITIS
Authors: T. Pilgaard, B. A. Esbensen, S. E. Stallknecht
Journal: Annals of the Rheumatic Diseases (2020)

Background: Limited data exist of work productivity loss in patients with Rheumatoid Arthritis (RA), Psoreatic Arthritis (PsA) and Spondyloarthritis (axSpA). Objectives: The objective of this research was to assess productivity loss and absenteeism in patients with RA, PsA and axSpA. Methods: The study was designed as a cross-sectional study aimed to collect patient-reported outcomes from patients with RA, PsA and axSpA in Denmark via a nurse administered questionnaires and patient journals. Patients ≥18 years with RA, PsA or axSpA were consecutively recruited for the study over a 6-month period via routine visits to outpatient rheumatology clinics. Descriptive statistics were analyzed using SAS. Results: Of 488 respondents, 62% were women and mean age was 53.5 years (RA:57.4; PsA:52.6; axSpA:43.6). Average time since diagnosis was 11-15 years, however, for PsA and axSpA most patients answered 6-10 and 0-5 years, respectively. 280 (57%) answered that they had a job and completed the WPAI questionnaire (RA: 149 (51%); PsA: 48 (56%); axSpA: 83 (75%)). Average work hours was 31.9 in the last week (RA:31.2; PsA:33; axSpA:32.4). Average missed work hours were 4.3 in the last 7 days ((RA:4.0; PsA:4.2; axSpA:4.8), of which 32% was missed due to their inflammatory arthritis (RA:30%; PsA:38%; axSpA:32%). Mean absenteeism was highest for patients with PsA (mean=6.8; SD=17.7) followed by patients with axSpA (mean=5.4; SD=15.1) and with RA (mean=3.4; SD=12.2). Mean productivity loss was 20.5 (SD=23.8) for patients with RA, 27.6 (SD=25.8) for PsA and 26.3 (SD=25.8) for axSpA Conclusion: We found that patients with PsA or axSpA miss more hours of work compared with patients with RA and when they are at work they have a higher absenteeism/lower productivity. This even though that both the group of patients with PsA and the axSpA were younger and had lived less time with their diagnosed disease compared with the group with RA. Disclosure of Interests: Trine Pilgaard Shareholder of: Pfizer, Employee of: Pfizer, Bente Appel Esbensen: None declared, Sandra Elkjær Stallknecht Consultant of: Pfizer
Abstract 13496: Genotype-First Analysis of TTR Variant Carriers Identifies Novel Traits Associated With Heritable Amyloidosis
Authors: Amy R Kontorovich, Alexandra McClellan, Sinead Cullina, Gillian Belbin, Peter Gorevic, Eimear Kenny, Noura Abul-Husn
Journal: Circulation (2019)

Introduction: Heritable amyloidosis due to transthyretin (TTR) gene variants (hATTR) is a systemic disorder causing polyneuropathy (PN) and cardiomyopathy (CMP). Symptoms are insidious and non-spec...
Why COVID-19 Silent Hypoxemia Is Baffling to Physicians
Authors: Martin J. Tobin, Franco Laghi, Amal Jubran
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Patients with coronavirus disease (COVID-19) are described as exhibiting oxygen levels incompatible with life without dyspnea. The pairing-dubbed happy hypoxia but more precisely termed silent hypoxemia-is especially bewildering to physicians and is considered as defying basic biology. This combination has attracted extensive coverage in media but has not been discussed in medical journals. It is possible that coronavirus has an idiosyncratic action on receptors involved in chemosensitivity to oxygen, but well-established pathophysiological mechanisms can account for most, if not all, cases of silent hypoxemia. These mechanisms include the way dyspnea and the respiratory centers respond to low levels of oxygen, the way the prevailing carbon dioxide tension (Pa
Nanopore sequencing as a scalable, cost-effective platform for analyzing polyclonal vector integration sites following clinical T cell therapy
Authors: Ping Zhang, Devika Ganesamoorthy, Son Hoang Nguyen, Raymond Au, Lachlan J Coin, Siok-Keen Tey
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Analysis of vector integration sites in gene-modified cells can provide critical information on clonality and potential biological impact on nearby genes. Current short-read next-generation sequencing methods require specialized instruments and large batch runs. Methods We used nanopore sequencing to analyze the vector integration sites of T cells transduced by the gammaretroviral vector, SFG.iCasp9.2A.ΔCD19. DNA from oligoclonal cell lines and polyclonal clinical samples were restriction enzyme digested with two 6-cutters, NcoI and BspHI ; and the flanking genomic DNA amplified by inverse PCR or cassette ligation PCR. Following nested PCR and barcoding, the amplicons were sequenced on the Oxford Nanopore platform. Reads were filtered for quality, trimmed, and aligned. Custom tool was developed to cluster reads and merge overlapping clusters. Results Both inverse PCR and cassette ligation PCR could successfully amplify flanking genomic DNA, with cassette ligation PCR showing less bias. The 4.8 million raw reads were grouped into 12,186 clusters and 6410 clones. The 3′long terminal repeat (LTR)-genome junction could be resolved within a 5-nucleotide span for a majority of clusters and within one nucleotide span for clusters with ≥5 reads. The chromosomal distributions of the insertional sites and their predilection for regions proximate to transcription start sites were consistent with previous reports for gammaretroviral vector integrants as analyzed by short-read next-generation sequencing. Conclusion Our study shows that it is feasible to use nanopore sequencing to map polyclonal vector integration sites. The assay is scalable and requires minimum capital, which together enable cost-effective and timely analysis. Further refinement is required to reduce amplification bias and improve single nucleotide resolution.
Biotherapeutics: Bone Scaffolds Based on Degradable Vaterite/PEG‐Composite Microgels (Adv. Healthcare Mater. 11/2020)
Authors: Elena Stengelin, Alena Kuzmina, Guillermo L. Beltramo, Martha F. Koziol, Laura Besch, Romina Schröder, Ronald E. Unger, Wolfgang Tremel, Sebastian Seiffert
Journal: Advanced Healthcare Materials (2020)

In article number 1901820 by Sebastian Seiffert and co-workers, degradable vaterite/PEG-composite microgels are templated by droplet-based microfluidic technology. A key aspect of the material development is the fundamental understanding of the gel structure-property relationships, and their connection to tissue engineering, by tailoring the microgel properties on micro-, meso-, and macroscopic levels. The co-encapsulation of cells provides an in vitro platform for metabolic bone regeneration studies and a step towards new bone tissue regeneration materials.
Abstract A33: Fungal beta-glucans, EphA2, and oral cancer: Preliminary observations
Authors: Sara Maskal, Santosh Ghosh, Chad Zender, Jason Thuener, Aaron Weinberg
Journal: Clinical Cancer Research (2020)

Abstract Introduction: Although Candida spp. are associated with invasive candidiasis in immunocompromised hosts, rates of asymptomatic colonization with the fungus are high. Candida has been associated with a variety of cancers and is thought to play a role in carcinogenesis. Beta glucans are polysaccharide components of the fungal cell wall that are more highly expressed in the more invasive, hyphal form of Candida. Recent data suggests that EPHA2, a tyrosine kinase receptor on oral epithelial cells, acts as a pattern recognition receptor for beta-glucans. We tested the hypothesis that beta-glucans promote proliferation and/or migration of squamous cell carcinoma cells through interactions with EPHA2. Methods: W18 cells, with wild-type EPHA2 expression, were derived from murine squamous cell carcinoma cells induced by classical DMBA/TPA protocol. SCC-728 is a squamous cell carcinoma cell line from an EphA2 KO mouse. The SCC-728 cell line was also used to generate an EPHA2-reconstituted cell line. HIGK cells are an immortalized oral epithelial cell line. Cells were cultured in 6 well plates to confluence in DMEM at 37° Celsius. Plates were scratched using a 200-microliter pipette tip and treated. Microscopic images from 0 and 24 hours were compared and analyzed visually by ImageJ. Beta-glucan from Saccharomyces was tested at 12.5 micrograms/milliliter. EGF (20 nanograms/milliliter) was the positive control for cell proliferation. Mitomycin C (10micrograms/milliliter) was the negative control for proliferation. Other glucans tested include zymosan (12.5 micrograms/milliliter) and pullulans (12.5 micrograms/milliliter). Results In the presence of beta-glucan, wild-type SCC cells (p&amp;lt;0.05) and EPHA2-reconstitued cells showed significant closure compared to control. EPHA2-KO cells did not show significant closure compared to controls on exposure to beta-glucans. All cell lines showed significant closure on treatment with EGF. Treatment with mitomycin C, alone or in combination with EGF or beta-glucan, prevented significant closure in all cell lines. Significant closure was seen with zymosan- and pullulans-treated cells. Conclusion: SCC cells showed increased proliferation in the presence of beta-1,6-glucan and beta-1,3-glucan from Saccharomyces. SCC cells showed migration or proliferation in the presence of alpha-1,4- and alpha-1,6-glucan, but less significant than beta-1,6-glucan and beta-1,3-glucan. Beta-glucan can induce EphA2-dependent cell membrane retraction similar to its native ligands. Citation Format: Sara Maskal, Santosh Ghosh, Chad Zender, Jason Thuener, Aaron Weinberg. Fungal beta-glucans, EphA2, and oral cancer: Preliminary observations [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr A33.