tbuckley/cabot-search huggingface dataset:
Characterizing heterogeneity in <i>KRAS</i> mutant colorectal cancers (CRC) using cellular, mutation, and immune profiles.
Authors: Anguraj Sadanandam, Pawan Poudel, Elisa Fontana, Chanthirika Ragulan
Journal: Journal of Clinical Oncology (2018)

657 Background: Approximately 30%-50% of CRC patients have KRAS mutation, and they are associated with lack of treatment response to anti-EGFR therapy. KRAS mutant CRCs are heterogeneous that not all mutant tumors are dependent on its downstream signaling. At this era of the search for therapeutic targets related to mutant KRAS, it is essential to understand the underlying heterogeneity in KRAS mutant metastatic CRCs with a goal of identifying personalized therapeutic vulnerabilities. To understand KRAS mutation further, in this study we classified KRAS mutant CRCs based on individual cell types in the normal colon crypt and associated them with PIK3CA mutations and interferon-gamma responsive signature. Methods: Publicly available RNAseq gene expression data from KRAS mutant samples were used. Classification of CRC samples into CRCassigner subtypes, KRAS mutation dependents/independent groups, and interferon gamma-responsive status was performed using published signatures. Results: CRC samples (n&gt;200) with KRAS mutant and wild-type statuses were classified into all the five CRCAssigner subtypes (goblet-like, enterocyte, transit-amplifying, stem-like and inflammatory) that represent individual cell types in the normal colon crypt. Interestingly, goblet-like subtype was found to be enriched for KRAS mutation. Among those KRAS mutant CRCs from all the subtypes (n=61), goblet-like samples showed significant enrichment (false discovery rate &lt;0.05; hypergeometric test) for KRAS dependent signature, whereas stem-like subtype showed KRAS independent signature. KRAS independent stem-like CRCs showed increased PIK3CA mutation and expression of interferon-gamma responsive genes compared to dependent CRCs. Conclusions: Overall, KRAS mutant CRCs are heterogeneous with differentiated subtype highly dependent on the mutation and its signalling pathway, whereas less differentiated/stem-like subtype CRCs are independent of the mutation. Also, the enrichment of PIK3CA mutation and interferon-gamma responsive genes mainly in KRAS independent CRC subtype present a potential opportunity to target them using combination immunotherapeutics.
Characterization of patients with Both Alcoholic and Nonalcoholic Fatty Liver Disease (BAFLD) in a large United States cohort
Authors: N. Alkhouri, A. Singh, A. Vigni, M. Noureddin, R. Lopez, K. Watt, E. Lawitz, F. Poordad, K.V. Kowdley
Journal: Journal of Hepatology (2018)
Donor liver small droplet macrovesicular steatosis is associated with reduced graft survival after liver transplantation
Authors: F. Ferri, A. Molinaro, E. Poli, L. Parlati, B. Lattanzi, G. Mennini, F. Melandro, F. Nudo, F. Pugliese, F. Maldarelli, A. Corsi, M. Riminucci, M. Merli, M. Rossi, S.G. Corradini
Journal: Journal of Hepatology (2018)
PER-ORAL ENDOSCOPIC MYOTOMY (POEM) AND PER ORAL ENDOSCOPIC PYLOROMYOTOMY (POEP) FOR COEXISTING GASTROPARESIS AND ACHALASIA IN A SINGLE PATIENT PERFORMED AS A SINGLE PROCEDURE
Authors: D Erhartova, Z Vackova, R Hustak, J Spicak, J Martinek
Journal: Endoscopy (2018)

POEM may be considered as a standard method for treatment of oesophageal achalasia and POEP represents an emerging new endoscopic method for treatment of refractory gastroparesis. We demonstrate successful concomitant POEM and POEP in a patient with co-existing achalasia (type II) and refractory gastroparesis.
New therapeutic opportunities from dissecting the pre-B leukemia bone marrow microenvironment
Authors: Laurence C. Cheung, Jennifer Tickner, Anastasia M. Hughes, Patrycja Skut, Meegan Howlett, Bree Foley, Joyce Oommen, Julia E. Wells, Bo He, Sajla Singh, Grace-Alyssa Chua, Jette Ford, Charles G. Mullighan, Rishi S. Kotecha, Ursula R. Kees
Journal: Leukemia (2018)

The microenvironments of leukemia and cancer are critical for multiple stages of malignancies, and they are an attractive therapeutic target. While skeletal abnormalities are commonly seen in children with acute lymphoblastic leukemia (ALL) prior to initiating osteotoxic therapy, little is known about the alterations to the bone marrow microenvironment during leukemogenesis. Therefore, in this study, we focused on the development of precursor-B cell ALL (pre-B ALL) in an immunocompetent BCR-ABL1+ model. Here we show that hematopoiesis was perturbed, B lymphopoiesis was impaired, collagen production was reduced, and the number of osteoblastic cells was decreased in the bone marrow microenvironment. As previously found in children with ALL, the leukemia-bearing mice exhibited severe bone loss during leukemogenesis. Leukemia cells produced high levels of receptor activator of nuclear factor κB ligand (RANKL), sufficient to cause osteoclast-mediated bone resorption. In vivo administration of zoledronic acid rescued leukemia-induced bone loss, reduced disease burden and prolonged survival in leukemia-bearing mice. Taken together, we provide evidence that targeting leukemia-induced bone loss is a therapeutic strategy for pre-B ALL.
Microbial ecology perturbation in human IgA deficiency
Authors: Jehane Fadlallah, Hela El Kafsi, Delphine Sterlin, Catherine Juste, Christophe Parizot, Karim Dorgham, Gaëlle Autaa, Doriane Gouas, Mathieu Almeida, Patricia Lepage, Nicolas Pons, Emmanuelle Le Chatelier, Florence Levenez, Sean Kennedy, Nathalie Galleron, Jean-Paul Pais de Barros, Marion Malphettes, Lionel Galicier, David Boutboul, Alexis Mathian, Makoto Miyara, Eric Oksenhendler, Zahir Amoura, Joel Doré, Claire Fieschi, S. Dusko Ehrlich, Martin Larsen, Guy Gorochov
Journal: Science Translational Medicine (2018)

IgA influences bacterial fitness in the intestinal lumen and is only partially compensated for by IgM in selective IgA-deficient patients.
Modeling serum HBsAg, HBV DNA and transaminase kinetics during REP 2139 monotherapy in chronic HBeAg+ HBV infection
Authors: L. Shekhtman, N. Borochov, S. Cotler, L. Hershkovich, S. Uprichard, M. Al-Mahtab, M. Bazinet, A. Vaillant, H. Dahari
Journal: Journal of Hepatology (2018)
Hepatitis C Virus (Japanese Version)
Authors: Arthur Kim
Journal: Annals of Internal Medicine (2016)

In the Clinic6 September 2016Hepatitis C Virus (Japanese Version)Correction(s) for this article:CorrectionsNov 2022Correction: Japanese Translations of In the ClinicFREEArthur Kim, MDArthur Kim, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/IsTranslatedFrom_AITC201609060_Japanese SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Editors' Note: This article (available in PDF format) is the translated Japanese version of In the Clinic: Hepatitis C Virus (Kim A. Hepatitis C Virus. Ann Intern Med. 2016;165:ITC33-ITC48. doi:10.7326/AITC201609060). Author, Article, and Disclosure InformationAffiliations: Correction: This article was updated on 1 November 2022 to remove the glossary of terms, which was not present on the original publication, and to indicate the translators of the article.Funding Source: American College of Physicians.Disclosures: Arthur Kim, MD, ACP Contributing Author, reports grants from National Institutes of Health, personal fees from Bristol-Myers Squibb, personal fees from AbbVie Pharmaceuticals, and grants and personal fees from Gilead Sciences during the conduct of the study. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M16-0134.With the assistance of additional physician writers, the editors of Annals of Internal Medicine develop In the Clinic using MKSAP and other resources of the American College of Physicians.In the Clinic does not necessarily represent official ACP clinical policy. For ACP clinical guidelines, please go to https://www.acponline.org/clinical_information/guidelines/. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoHepatitis C Virus Arthur Kim Correction: Japanese Translations of In the Clinic Metrics Cited byCorrection: Japanese Translations of In the Clinic 6 September 2016Volume 165, Issue 5Page: JITC33-JITC48 ePublished: 17 April 2018 Issue Published: 6 September 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Comparison of conventional ultrasound signs to current state-of-the-art MRI method for detection of hepatic steatosis
Authors: M.M. Kim, D.W. Jun, B.-K. Kang, Y.C. Joo, H. Oh, E.C.J. Jang, J.H. Sohn, J.Y. Jeong, S.B. Ahn
Journal: Journal of Hepatology (2018)
The Alchemist’s Nightmare
Authors: Milton Packer
Journal: Circulation (2018)

The injection of mesenchymal stem cells into the injured myocardium to induce cardiac regeneration has yielded disappointing results, conceivably because cells with cardioreparative potential must be supplied for long periods of time to produce a salutary effect. Accordingly, investigators have devised ways of directing such cells to the heart on an ongoing basis: by enhancing the action of endogenous peptides that function as cardiac homing signals (eg, stromal cell-derived factor-1). Stromal cell-derived factor-1 is released during acute cardiac injury and heart failure, but it has a short half-life because of degradation by dipeptidyl peptidase-4. Inhibition of dipeptidyl peptidase-4 potentiates the actions of stromal cell-derived factor-1 and, theoretically, could enhance cardiac recovery. However, in large-scale trials in patients with type 2 diabetes mellitus, dipeptidyl peptidase-4 inhibitors have not reduced the risk of atherosclerotic ischemic events, and they have unexpectedly increased the risk of heart failure, most probably heart failure with a preserved ejection fraction. Such an outcome might be explained if the channeling of mesenchymal stem cells to the heart by the actions of stromal cell-derived factor-1 (especially from nearby adipose tissue) were followed by the transformation of these cells into fibroblasts rather than cardiomyocytes. This concern has been supported by experimental studies; the resulting fibrosis would be expected to exacerbate the pathophysiological derangements that lead to heart failure with a preserved ejection fraction. Given the widespread use of dipeptidyl peptidase-4 inhibitors, the possibility that these drugs potentiate the cardiac homing of mesenchymal stem cells that cause myocardial fibrosis (rather than repair) warrants further study.
Comparative Study of Two Droplet‐Based Dissolving Microneedle Fabrication Methods for Skin Vaccination
Authors: Chisong Lee, Hongil Kim, Suyong Kim, Shayan F. Lahiji, Na‐Young Ha, Huisuk Yang, Geonwoo Kang, Hai Yen Thi Nguyen, Yuri Kim, Myung‐Sik Choi, Nam‐Hyuk Cho, Hyungil Jung
Journal: Advanced Healthcare Materials (2018)

Abstract Dissolving microneedles (DMNs) have been widely studied in medical applications due to their pain‐free administration, superior efficiency, and safe drug delivery. In skin vaccination, preserving the activity of the encapsulated antigen is an important consideration, as antigen activity is lost during DMN fabrication because of various stress factors. These stress factors vary between fabrication methods and each method affects the antigen's activity to different degrees. In this study, the activity of encapsulated antigens delivered by DMNs is compared between two recently developed DMN fabrication methods; droplet‐born air blowing (DAB) and centrifugal lithography (CL) for a model scrub typhus vaccine antigen, ScaA. Although the in vitro analysis of ScaA‐loaded DMNs (ScaA‐DMNs) does not show any differences in physical properties depending on the fabrication methods, the immunogenicity of the CL‐produced ScaA‐DMN is significantly higher based on cytokine measurement and humoral immunity. DAB and CL differ in their solidification conditions, suggesting that solidification factors critically affect the encapsulated antigen's activity. ScaA‐DMNs may also be stably stored for 4 weeks at room temperature. In conclusion, CL is a superior DMN fabrication method compared with DAB, and this study proves that DMN is feasible and practical for skin vaccination.
Diabetes After Hormone Therapy in Breast Cancer Survivors: A Case-Cohort Study
Authors: Rola Hamood, Hatem Hamood, Ilya Merhasin, Lital Keinan-Boker
Journal: Journal of Clinical Oncology (2018)

Purpose Breast cancer treatments have been associated with an increased risk of multiple health-related adverse outcomes, but the relationship with diabetes remains unclear. This study investigated the association between hormone therapy and diabetes risk in breast cancer survivors. Patients and Methods We performed a case-cohort study of 2,246 female survivors recruited from the Leumit health care fund who were diagnosed with primary nonmetastatic invasive breast cancer in 2002 through 2012. A 20% random subcohort was sampled at baseline, and all diabetes cases were identified. Adjusted hazard ratios (HRs) with 95% CIs were estimated by weighted Cox proportional hazards regression models. Results Of 2,246 breast cancer survivors, 324 developed diabetes over a mean follow-up of 5.9 years. The crude cumulative incidence of diabetes that accounted for death as a competing risk was 20.9% (95% CI, 18.3% to 23.7%). In multivariable-adjusted models, hormone therapy was associated with increased diabetes risk (HR, 2.40; 95% CI, 1.26 to 4.55; P = .008). The hazard for tamoxifen use (HR, 2.25; 95% CI, 1.19 to 4.26; P = .013) was less pronounced than the use of aromatase inhibitors (HR, 4.27, 95% CI, 1.42 to 12.84; P = .010). Conclusion Active hormone therapy is a significant risk factor of diabetes among breast cancer survivors. Although cessation of treatment is not recommended because the survival benefits of hormone therapy outweigh the risks, preventive strategies aimed at lifestyle modifications may minimize the risk.
Risk of Dementia Outcomes Associated With Traumatic Brain Injury During Military Service
Authors: Kimbra Kenney, Ramon Diaz-Arrastia
Journal: JAMA Neurology (2018)

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 Neurology 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 Neurology journal
Behavioral and clinical factors and Direct Acting Antiviral effectiveness in HCV/HIV co-infection; clinical experience from the TRIO network
Authors: G. Huhn, D. Jayaweera, K. Althoff, J. Eron, S. Milligan, A. Mills, G. Moyle, S. Santiago, P. Sax, G. Voskuhl, D. Wyles, R. Elion
Journal: Journal of Hepatology (2018)
The Power of Trust
Authors: Eric Mou, Lidia Schapira, Pamela Kunz
Journal: JAMA Oncology (2018)

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 Oncology 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 Oncology journal
Standardized reporting of the Eczema Area and Severity Index (EASI) and the Patient-Oriented Eczema Measure (POEM): a recommendation by the Harmonising Outcome Measures for Eczema (HOME) Initiative
Authors: E.E. Grinich, J. Schmitt, D. Küster, P.I. Spuls, H.C. Williams, J.R. Chalmers, K.S. Thomas, C. Apfelbacher, C.A.C. Prinsen, M. Furue, B. Stuart, B. Carter, E.L. Simpson
Journal: British Journal of Dermatology (2018)

Several organizations from multiple fields of medicine are setting standards for clinical research including protocol development,1 harmonization of outcome reporting,2 statistical analysis,3 quality assessment4 and reporting of findings.1 Clinical research standardization facilitates the interpretation and synthesis of data, increases the usability of trial results for guideline groups and shared decision‐making, and reduces selective outcome reporting bias. The mission of the Harmonising Outcome Measures for Eczema (HOME) initiative is to establish an agreed‐upon core set of outcomes to be measured and reported in all clinical trials of atopic dermatitis (AD).
Review: Chikungunya Arthritis: Implications of Acute and Chronic Inflammation Mechanisms on Disease Management
Authors: Ali Zaid, Patrick Gérardin, Adam Taylor, Helen Mostafavi, Denis Malvy, Suresh Mahalingam
Journal: Arthritis & Rheumatology (2017)

In the past decade, arboviruses-arthropod-borne viruses-have been the focus of public health institutions worldwide following a spate of devastating outbreaks. Chikungunya virus, an arbovirus that belongs to the alphavirus genus, is a reemerging arthritogenic virus that has caused explosive outbreaks since 2006, notably on Réunion Island, and more recently in the Caribbean, South America, India, and Southeast Asia. The severity of arthritic disease caused by chikungunya virus has prompted public health authorities in affected countries to develop specific guidelines to tackle this pathogen. Chikungunya virus disease manifests first as an acute stage of severe joint inflammation and febrile illness, which later progresses to a chronic stage, during which patients may experience debilitating and persisting articular pain for extended periods. This review aims to provide a broad perspective on current knowledge of chikungunya virus pathogenesis by identifying key clinical and experimental studies that have contributed to our understanding of chikungunya virus to date. In addition, the review explores the practical aspects of treatment and management of both acute and chronic chikungunya virus based on clinical experience during chikungunya virus outbreaks. Finally, recent findings on potential therapeutic solutions-from antiviral agents to immunomodulators-are reviewed to provide both viral immunologists and clinical rheumatologists with a balanced perspective on the nature of a reemerging arboviral disease of significant public health concern, and insight into future therapeutic approaches to better address the treatment and management of chikungunya virus.
Efficacy of a Carrageenan gel Against Transmission of Cervical HPV (CATCH): interim analysis of a randomized, double-blind, placebo-controlled, phase 2B trial
Authors: S. Magnan, J.E. Tota, M. El-Zein, A.N. Burchell, J.T. Schiller, A. Ferenczy, P.-P. Tellier, F. Coutlée, E.L. Franco, A. Rodrigues, N. Morykon, R. Rodrigues, S. Bouten, S. Shapiro, J. Guénoun, N. Slavetchva
Journal: Clinical Microbiology and Infection (2018)
Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses
Authors: Norbert Pardi, Michael J. Hogan, Martin S. Naradikian, Kaela Parkhouse, Derek W. Cain, Letitia Jones, M. Anthony Moody, Hans P. Verkerke, Arpita Myles, Elinor Willis, Celia C. LaBranche, David C. Montefiori, Jenna L. Lobby, Kevin O. Saunders, Hua-Xin Liao, Bette T. Korber, Laura L. Sutherland, Richard M. Scearce, Peter T. Hraber, István Tombácz, Hiromi Muramatsu, Houping Ni, Daniel A. Balikov, Charles Li, Barbara L. Mui, Ying K. Tam, Florian Krammer, Katalin Karikó, Patricia Polacino, Laurence C. Eisenlohr, Thomas D. Madden, Michael J. Hope, Mark G. Lewis, Kelly K. Lee, Shiu-Lok Hu, Scott E. Hensley, Michael P. Cancro, Barton F. Haynes, Drew Weissman
Journal: The Journal of Experimental Medicine (2018)

T follicular helper (Tfh) cells are required to develop germinal center (GC) responses and drive immunoglobulin class switch, affinity maturation, and long-term B cell memory. In this study, we characterize a recently developed vaccine platform, nucleoside-modified, purified mRNA encapsulated in lipid nanoparticles (mRNA-LNPs), that induces high levels of Tfh and GC B cells. Intradermal vaccination with nucleoside-modified mRNA-LNPs encoding various viral surface antigens elicited polyfunctional, antigen-specific, CD4+ T cell responses and potent neutralizing antibody responses in mice and nonhuman primates. Importantly, the strong antigen-specific Tfh cell response and high numbers of GC B cells and plasma cells were associated with long-lived and high-affinity neutralizing antibodies and durable protection. Comparative studies demonstrated that nucleoside-modified mRNA-LNP vaccines outperformed adjuvanted protein and inactivated virus vaccines and pathogen infection. The incorporation of noninflammatory, modified nucleosides in the mRNA is required for the production of large amounts of antigen and for robust immune responses.
Trehalose-Induced Activation of Autophagy Improves Cardiac Remodeling After Myocardial Infarction
Authors: Sebastiano Sciarretta, Derek Yee, Narayani Nagarajan, Franca Bianchi, Toshiro Saito, Valentina Valenti, Mingming Tong, Dominic P. Del Re, Carmine Vecchione, Leonardo Schirone, Maurizio Forte, Speranza Rubattu, Akihiro Shirakabe, V. Subbarao Boppana, Massimo Volpe, Giacomo Frati, Peiyong Zhai, Junichi Sadoshima
Journal: Journal of the American College of Cardiology (2018)