tbuckley/cabot-search huggingface dataset:
Abstract A32: Adipose-derived mesenchymal stem cell has the differentiation/reprogramming capacity towards two distinct cancer-associated fibroblasts
Authors: Yoshihiro Miyazaki, Yutato Kumagai, Hiroko Kushige, Osamu Shimomura, Yasuyuki Kida, Tatsuya Oda
Journal: Cancer Research (2019)

Abstract Cancer-associated fibroblasts (CAFs) are well known of its heterogeneity with distinct phenotypes and functions in tumor progression. CAFs are believed to be composed mainly of resident tissue fibroblast, such as pancreas stellate cells, but bone marrow-derived mesenchymal stem cells (MSC) are also known to be their source (Ishii G et al., Adv Drug Deliv Rev 2016). Herein, we focus on adipose-derived MSC (AD-MSC) as an alternative source of CAF, as one has high reactivity of differentiation and reprogramming to the many cell types (Ronnov-Jessen L et al., J Clin Invest 1995; Sugii/Kida et al., PNAS 2010). It was reported that CAFs include myofibroblastic CAFs (myCAFs), which are found adjacent to tumor cells, and inflammatory CAFs (iCAFs), which localize farther away within the dense stroma (Ohlund, Tuveson et al., J Exp Med 2017). We investigated whether AD-MSC can be a CAF progenitor and differentiated to the different subpopulations of CAFs by employing different culture condition. To evaluate the differentiation capacity, a GFP labeled AD-MSC cell line and the human pancreatic-cancer cell line (Capan-1) were co-cultured in two condition, including direct (DR) co-culture or indirect transwell (TW) co-culture. We then performed qRT-PCR analysis and immunocytochemistry to examine their myCAF marker (ACTA-2, CTGF) or iCAF markers (IL-6, CXCL1, LIF) and compared with those in monocultured AD-MSC. We also analyzed in vitro tumor formation in DR co-culture using time-lapse imaging. In DR co-culture, the morphology of Capan-1 and AD-MSC recapitulated the clinical pancreatic cancer, with those CAF markers expressions. In the course of co-culture, sequential morphologic alterations were observed in AD-MSCs. The AD-MSC with stellate shape changed to large and small spindle-like cells through crosstalk with cancer cells. In sharp contrast, only iCAF marker expression was elevated in TW co-culture. These results collectively suggest that the AD-MSC have a potential to be progenitors of both myCAF and iCAF, explaining the heterogeneity of CAFs under the direct crosstalk with cancer cells. In the presentation, we discuss the differentiation/reprogramming capacity of AD-MSC towards two distinct CAFs (i.e., myCAF and iCAF), focusing on the cell morphology and RNA-seq analysis. Citation Format: Yoshihiro Miyazaki, Yutato Kumagai, Hiroko Kushige, Osamu Shimomura, Yasuyuki Kida, Tatsuya Oda. Adipose-derived mesenchymal stem cell has the differentiation/reprogramming capacity towards two distinct cancer-associated fibroblasts [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr A32.
The Impact of Mentorship
Authors: Bonnie Ky, MD, MSCE, FACC
Journal: JACC CardioOncology (2019)

![Figure][1] 

My breath in is gratitude, and my breath out is helping others.—Shared by Dr. Kalpana and Uday Patankar

In my role as the Editor-in-Chief of JACC: CardioOncology, I am driven by the tremendous opportunity to inform and advance the fields of cardiology and oncology,
Abstract B02: Tissue-specific innate lymphoid cells are novel targets for pancreatic cancer immunotherapy
Authors: Joanne Leung, Luis A Rojas, Jennifer Ruan, Julia Zhao, Billel Gasmi, Zachary Sethna, Anita Ramnarain, Umesh Bhanot, Gokce Askan, Murali Gururajan, Ela Elyada, Youngkyu Park, David A. Tuveson, Mithat Gonen, Steven D. Leach, Jedd D. Wolchok, Ronald P. DeMatteo, Taha Merghoub, Vinod P. Balachandran, John Alec Moral
Journal: Cancer Research (2019)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is the classic cold tumor, with few tumor-infiltrating activated CD8+ T cells, a major barrier to immunotherapy. Strategies to convert cold PDACs to hot can enable more effective immunotherapies. To identify targets that can convert cold PDACs to hot, we compared a large cohort of rare long-term PDAC survivors with hot tumors to short-term survivors with cold tumors. Surprisingly, hot PDACs were enriched not only in activated CD8+ T cells, but also in group-2 innate lymphoid cells (ILC2s), a class of largely tissue-resident, cytokine-producing innate lymphocyte that potentiates T cell immunity in local tissues. We identified that tumor ILC2s (TILC2s) infiltrate human and mouse PDACs, and TILC2 frequency and tumor expression of the ILC2-activating ligand interleukin (IL)-33 positively correlate with tumor immune cytolytic activity, and long-term patient survival. Using PDAC mouse models, we discovered that the IL33-ILC2 axis activates pancreatic tissue-specific antitumor T-cell immunity. Host IL33 deficiency attenuated TILC2 expansion and CD8+ T-cell activation, accelerating tumor growth in orthotopic PDACs but not heterotopic skin implanted PDACs where TILC2s lack the IL33 receptor. Acute ILC2 depletion partially phenocopied the tissue-specific phenotype of IL33 deficiency, with impaired rejection of immunogenic orthotopic but not heterotopic skin PDACs. Treatment with recombinant IL33 (rIL33), but not with the ILC1-activating ligand rIL18, increased TILC2 frequencies, activated CD8+ T cells, and abrogated orthotopic but not heterotopic PDAC establishment in &amp;gt;70% of mice. Taken together, these studies identify ILC2s as novel anticancer immune cells for PDAC immunotherapy. Strategies to activate tissue-specific ILC2s may be a promising immunotherapeutic approach for PDAC. Citation Format: Joanne Leung, Luis A Rojas, Jennifer Ruan, Julia Zhao, Billel Gasmi, Zachary Sethna, Anita Ramnarain, Umesh Bhanot, Gokce Askan, Murali Gururajan, Ela Elyada, Youngkyu Park, David A. Tuveson, Mithat Gonen, Steven D. Leach, Jedd D. Wolchok, Ronald P. DeMatteo, Taha Merghoub, Vinod P. Balachandran, John Alec Moral. Tissue-specific innate lymphoid cells are novel targets for pancreatic cancer immunotherapy [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr B02.
Single-Cell Transcriptome Analysis Reveals Disease-Defining T-cell Subsets in the Tumor Microenvironment of Classic Hodgkin Lymphoma
Authors: Tomohiro Aoki, Lauren C. Chong, Katsuyoshi Takata, Katy Milne, Monirath Hav, Anthony Colombo, Elizabeth A. Chavez, Michael Nissen, Xuehai Wang, Tomoko Miyata-Takata, Vivian Lam, Elena Viganò, Bruce W. Woolcock, Adèle Telenius, Michael Y. Li, Shannon Healy, Chanel Ghesquiere, Daniel Kos, Talia Goodyear, Johanna Veldman, Allen W. Zhang, Jubin Kim, Saeed Saberi, Jiarui Ding, Pedro Farinha, Andrew P. Weng, Kerry J. Savage, David W. Scott, Gerald Krystal, Brad H. Nelson, Anja Mottok, Akil Merchant, Sohrab P. Shah, Christian Steidl
Journal: Cancer Discovery (2019)

Abstract Hodgkin lymphoma is characterized by an extensively dominant tumor microenvironment (TME) composed of different types of noncancerous immune cells with rare malignant cells. Characterization of the cellular components and their spatial relationship is crucial to understanding cross-talk and therapeutic targeting in the TME. We performed single-cell RNA sequencing of more than 127,000 cells from 22 Hodgkin lymphoma tissue specimens and 5 reactive lymph nodes, profiling for the first time the phenotype of the Hodgkin lymphoma–specific immune microenvironment at single-cell resolution. Single-cell expression profiling identified a novel Hodgkin lymphoma–associated subset of T cells with prominent expression of the inhibitory receptor LAG3, and functional analyses established this LAG3+ T-cell population as a mediator of immunosuppression. Multiplexed spatial assessment of immune cells in the microenvironment also revealed increased LAG3+ T cells in the direct vicinity of MHC class II–deficient tumor cells. Our findings provide novel insights into TME biology and suggest new approaches to immune-checkpoint targeting in Hodgkin lymphoma. Significance: We provide detailed functional and spatial characteristics of immune cells in classic Hodgkin lymphoma at single-cell resolution. Specifically, we identified a regulatory T-cell–like immunosuppressive subset of LAG3+ T cells contributing to the immune-escape phenotype. Our insights aid in the development of novel biomarkers and combination treatment strategies targeting immune checkpoints. See related commentary by Fisher and Oh, p. 342. This article is highlighted in the In This Issue feature, p. 327
Abstract 18222: Detection of Left Ventricular Assist Device Thrombosis Using a Fibrin Specific Probe
Authors: Justin C Hartupee, Grace Cui, Michael J Scott, Akinobu Itoh, Samuel Achilefu, Gregory M Lanza, Gregory A Ewald
Journal: Circulation (2017)

Introduction: Thromboembolic events (TE) and gastrointestinal bleeding (GIB) are frequent complications of LVAD implantation. Prevention of these events requires optimization of the anticoagulation...
The Elusive Nature of Delay Discounting as a Transdiagnostic Process in Psychiatric Disorders—The Devil Is in the Detail—Reply
Authors: Michael Amlung, Emma Marsden, Randi E. McCabe
Journal: JAMA Psychiatry (2019)

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 Psychiatry 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 Psychiatry journal
Understanding resolution of inflammation in periodontal diseases: Is chronic inflammatory periodontitis a failure to resolve?
Authors: Thomas E. Van Dyke, Corneliu Sima
Journal: Periodontology 2000 (2019)

Abstract Periodontitis is an infectious‐inflammatory disease that results from loss of balance between the commensal microbiome and the host response. The hyper‐inflammatory, uncontrolled inflammatory immune lesion promotes tissue damage and impedes effective bacterial clearance. In this review, the relationship between the microbiome and the inflammatory/immune response is explored in the context of a bi‐directional pathogenesis; bacteria induce inflammation and inflammation modifies the growth environment causing shifts in the composition of the microbiome. Resolution of inflammation is an active, receptor‐mediated process induced by specialized pro‐resolving lipid mediators. Inflammatory disease may, therefore, be the result of failure of resolution. Failure to resolve inflammation coupled with resultant microbiome changes is hypothesized to drive development of periodontitis. Re‐establishment of microbiome/host homeostasis by specialized pro‐resolving lipid mediator therapy suggests that microbiome dysbiosis, the host hyperinflammatory phenotype, and periodontitis can be reversed.
The 2016 California policy to eliminate nonmedical vaccine exemptions and changes in vaccine coverage: An empirical policy analysis
Authors: Sindiso Nyathi, Hannah C. Karpel, Kristin L. Sainani, Yvonne Maldonado, Peter J. Hotez, Eran Bendavid, Nathan C. Lo
Journal: PLoS Medicine (2019)

Vaccine hesitancy, the reluctance or refusal to receive vaccination, is a growing public health problem in the United States and globally. State policies that eliminate nonmedical ("personal belief") exemptions to childhood vaccination requirements are controversial, and their effectiveness to improve vaccination coverage remains unclear given limited rigorous policy analysis. In 2016, a California policy (Senate Bill 277) eliminated nonmedical exemptions from school entry requirements. The objective of this study was to estimate the association between California's 2016 policy and changes in vaccine coverage.
Pharmacology and Therapeutics of Bronchodilators Revisited
Authors: M. G. Matera, C. P. Page, L. Calzetta, P. Rogliani, M. Cazzola
Journal: Pharmacological Reviews (2019)

Bronchodilators remain the cornerstone of the treatment of airway disorders such as asthma and chronic obstructive pulmonary disease (COPD). There is therefore considerable interest in understanding how to optimize the use of our existing classes of bronchodilator and in identifying novel classes of bronchodilator drugs. However, new classes of bronchodilator have proved challenging to develop because many of these have no better efficacy than existing classes of bronchodilator and often have unacceptable safety profiles. Recent research has shown that optimization of bronchodilation occurs when both arms of the autonomic nervous system are affected through antagonism of muscarinic receptors to reduce the influence of parasympathetic innervation of the lung and through stimulation of <i>β</i><sub>2</sub>-adrenoceptors (<i>β</i><sub>2</sub>-ARs) on airway smooth muscle with <i>β</i><sub>2</sub>-AR–selective agonists to mimic the sympathetic influence on the lung. This is currently achieved by use of fixed-dose combinations of inhaled long-acting <i>β</i><sub>2</sub>-adrenoceptor agonists (LABAs) and long-acting muscarinic acetylcholine receptor antagonists (LAMAs). Due to the distinct mechanisms of action of LAMAs and LABAs, the additive/synergistic effects of using these drug classes together has been extensively investigated. More recently, so-called "triple inhalers" containing fixed-dose combinations of both classes of bronchodilator (dual bronchodilation) and an inhaled corticosteroid in the same inhaler have been developed. Furthermore, a number of so-called "bifunctional drugs" having two different primary pharmacological actions in the same molecule are under development. This review discusses recent advancements in knowledge on bronchodilators and bifunctional drugs for the treatment of asthma and COPD. <h3>SIGNIFICANCE STATEMENT</h3> Since our last review in 2012, there has been considerable research to identify novel classes of bronchodilator drugs, to further understand how to optimize the use of the existing classes of bronchodilator, and to better understand the role of bifunctional drugs in the treatment of asthma and chronic obstructive pulmonary disease.
Crohn Disease–Associated Genital Edema
Authors: Reese L. Imhof, Megha M. Tollefson
Journal: JAMA Dermatology (2019)

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 Dermatology 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 Dermatology journal
Endoscopic ultrasound-guided fine-needle aspiration and fine-needle biopsy for solid lesions: Does a “belt and suspenders” approach add value?
Authors: Douglas G. Adler
Journal: Endoscopy (2019)

For over two decades, endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has been the standard means of sampling both solid and cystic lesions of the luminal gastrointestinal tract, the pancreas, and surrounding structures. Rapid onsite evaluation (ROSE) of cytological samples has also been employed at the majority of centers performing EUS, and has been shown to increase tissue adequacy rates as well as provide clinicians and patients with a diagnosis in real time [1].
Single-cell analysis of human adipose tissue identifies depot- and disease-specific cell types
Authors: Jinchu Vijay, Marie-Frédérique Gauthier, Rebecca L. Biswell, Daniel A. Louiselle, Jeffrey J. Johnston, Warren A. Cheung, Bradley Belden, Albena Pramatarova, Laurent Biertho, Margaret Gibson, Marie-Michelle Simon, Haig Djambazian, Alfredo Staffa, Guillaume Bourque, Anita Laitinen, Johanna Nystedt, Marie-Claude Vohl, Jason D. Fraser, Tomi Pastinen, André Tchernof, Elin Grundberg
Journal: Nature Metabolism (2019)
Quantifying atrial anatomy uncertainty from clinical data and its impact on electro-physiology simulation predictions
Authors: Cesare Corrado, Orod Razeghi, Caroline Roney, Sam Coveney, Steven Williams, Iain Sim, Mark O’Neill, Richard Wilkinson, Jeremy Oakley, Richard H. Clayton, Steven Niederer
Journal: Medical Image Analysis (2019)

Patient-specific computational models of structure and function are increasingly being used to diagnose disease and predict how a patient will respond to therapy. Models of anatomy are often derived after segmentation of clinical images or from mapping systems which are affected by image artefacts, resolution and contrast. Quantifying the impact of uncertain anatomy on model predictions is important, as models are increasingly used in clinical practice where decisions need to be made regardless of image quality. We use a Bayesian probabilistic approach to estimate the anatomy and to quantify the uncertainty about the shape of the left atrium derived from Cardiac Magnetic Resonance images. We show that we can quantify uncertain shape, encode uncertainty about the left atrial shape due to imaging artefacts, and quantify the effect of uncertain shape on simulations of left atrial activation times.
Identifying the ‘incredible’! Part 1: assessing the risk of bias in outcomes included in systematic reviews
Authors: Fionn Büttner, Marinus Winters, Eamonn Delahunt, Roy Elbers, Carolina B Lura, Karim M Khan, Adam Weir, Clare L Ardern
Journal: British Journal of Sports Medicine (2019)

Systematic reviews fulfil a vital role in modern medicine.1 However, the results of systematic reviews are only as valid as the studies they include.2 Pooling flawed, or biased, results from different studies can compromise the credibility of systematic review findings. Bias is a systematic deviation from the truth in the results of a research study that can manifest due to limitations in study design, conduct, or analysis.3

The results of sport and exercise medicine research, like results in other fields, are vulnerable to bias.4 It is important that systematic review authors assess for bias in a way that enables a judgement about whether a review outcome is at risk of bias due to methodological limitations in included studies. This two-part education primer focuses on how systematic review authors can perform and interpret risk of bias assessments to avoid misleading systematic review conclusions. In this editorial, we introduce the concept of risk of bias, and the principles of assessing risk of bias.

Different biases have effects that vary in direction and magnitude.3 5 It is challenging to precisely determine how bias may overestimate or underestimate a study’s true findings. In fact, bias does not always result in distorted study findings and one can never be certain that bias is present when a study has methodological limitations. However, methodological limitations in study design, conduct, or analysis can be consistently associated with inflated research findings.5 Due to this uncertainty, study outcomes are considered to be at risk of bias rather than ‘biased’.

Studies with ‘some concerns’ or at ‘high’ risk of bias in design, conduct, analysis, or reporting are at greater risk of inflated findings compared with studies at ‘low’ risk of bias, negatively …
Increasing Responses to T-Cell Therapies in Solid Tumours by the Use of an Engineered Adenovirus Coding for TNFa and IL-2
Authors: V. Cervera-Carrascon, R. Havunen, J.M. Santos, D.C.A. Quixabeira, A. Hemminki, S. Zafar
Journal: Annals of Oncology (2019)
Continuing Antipsychotic Medication for Patients With Psychotic Depression in Remission
Authors: Klaus Munkholm, Karsten Juhl Jørgensen, Asger Sand Paludan-Müller
Journal: JAMA (2019)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal