tbuckley/cabot-search huggingface dataset:
Abstract 1582: The coupling of MDSCs with a computational neural network (NN) to detect solid tumors
Authors: George A. Dominguez, Kristen Maslar, Alexander Polo, Cyrus Sholevar, Anthony Campisi, John Roop, Dmitry Gabrilovich, Frank Rauscher, Amit Kumar
Journal: Cancer Research (2018)

Abstract The goal of this study was to create a non-invasive cancer detection assay that analyzes flow cytometry data in an objective method. By using an artificial neural network (NN), we were able to distinguish between cancer patients (CPs) and benign/healthy donors (HDs) based upon the flow cytometry profiles of MDSCs and other leukocytes. Myeloid-derived suppressor cells (MDSCs) are known to be key contributors in supporting tumor progression and tumor escape through their ability to suppress anti-tumor responses mediated through T cell and natural killer (NK) cell activity. Several studies have demonstrated their utility as indicators of tumor progression and possible predictors of clinical outcomes, but there is significant overlap with healthy individuals preventing discrete and accurate calls. We used standard multiparametric flow cytometry techniques to immunophenotype MDSCs and other leukocytes found in the peripheral blood of 65 biopsy-confirmed CPs with solid tumors and 84 HDs. A series of NNs utilizing pattern recognition computational algorithms are then created using three data sets: 1) the training set - this ‘teaches' the two output categories of cancer and not cancer, 2) the validation set - this uses backpropagation to improve the accuracy of the trained networks, and 3) the testing set - this is used to rank the trained networks against each other. Finally, a naïve testing set is then used to determine the overall sensitivity and specificity for the top-ranking networks. Using traditional flow cytometry gating methods to analyze MDSCs as a biomarker for cancer detection, it is difficult to achieve high sensitivity and specificity due to the substantial overlap with healthy individuals. Here, we incorporated a standard 12 marker flow cytometry assay with NN technology to achieve a sensitivity of 92% and a specificity of 89%. Pairing the advanced analytical capabilities of our NN with surface biomarker based analysis of MDSCs and certain leukocytes measured in peripheral blood has enabled us the ability to objectively identify patterns indicative for the existence of a solid tumor. Citation Format: George A. Dominguez, Kristen Maslar, Alexander Polo, Cyrus Sholevar, Anthony Campisi, John Roop, Dmitry Gabrilovich, Frank Rauscher, Amit Kumar. The coupling of MDSCs with a computational neural network (NN) to detect solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1582.
Amphiregulin-Producing Pathogenic Memory T Helper 2 Cells Instruct Eosinophils to Secrete Osteopontin and Facilitate Airway Fibrosis
Authors: Yuki Morimoto, Kiyoshi Hirahara, Masahiro Kiuchi, Tomoko Wada, Tomomi Ichikawa, Toshio Kanno, Mikiko Okano, Kota Kokubo, Atsushi Onodera, Daiju Sakurai, Yoshitaka Okamoto, Toshinori Nakayama
Journal: Immunity (2018)
Risk factors for recurrence in patients with Clostridium difficile infection due to 027 and non-027 ribotypes
Authors: M. Falcone, G. Tiseo, F. Iraci, G. Raponi, P. Goldoni, D. Delle Rose, I. Santino, P. Carfagna, R. Murri, M. Fantoni, C. Fontana, M. Sanguinetti, A. Farcomeni, G. Antonelli, A. Aceti, C. Mastroianni, M. Andreoni, R. Cauda, N. Petrosillo, M. Venditti
Journal: Clinical Microbiology and Infection (2018)
Abstract 27: Regulating Rac1 signaling proteins influences migratory and protrusive behaviors of metastatic breast cancer cells in aligned, 3D collagen and collagen-like matrices
Authors: Rachel Van Doorn, Joseph Szulczewski, Suzanne Ponik
Journal: Cancer Research (2018)

Abstract Breast cancer is the most commonly diagnosed cancer in women, with one out of every eight women being diagnosed in their lifetime. Our lab has previously shown that aligned collagen promotes tumor progression to metastatic disease, and predicts poor prognosis for breast cancer patients. Aligned collagen increases the persistence of cellular migration by limiting the number of protrusions from the cell body. The regulation of Rac1 and Rho proteins are important for cell motility through formation of lamelliepodia. Deregulation of these proteins and those upstream of Rac1, can result in cancer cell migration, invasion and metastases. Understanding how these proteins are regulated in different 3D collagen tumor microenvironments is important for determining phenotypes of invasive breast cancers. Inhibition of cell motility through the Rac1 pathway may limit cancer cell migration and prevent metastatic disease. While many studies have investigated cell migration in 2D, little is known regarding the cellular mechanisms that regulate both breast cancer cell migration and protrusive events in 3D aligned collagen. In vitro models will be used to recapitulate 3D aligned, and random collagen environments and assess the mechanisms of cell migration and protrusion dynamics by live-cell, time-lapse microscopy. Previous work from our group determined that MDA-MB-231 cells seeded into collagen environments had fewer protrusions, which localized in the directions of collagen alignment, when migrating along aligned fibers compared to MDA-MB-231 cells in the random collagen matrices. Preliminary data demonstrates that signaling proteins upstream of Rac1 such as, small GTPases, DOCK180 and FilGAP, dictate cellular protrusions and migratory persistence. MDA-MB-231 cell lines with doxycycline-induced knock-down Rac1 GTPase activating protein (GAP), FilGAP, and guanine nucleotide exchange factor (GEF), DOCK180, demonstrate that the regulation of Rac1 activity through these specific proteins plays a role in breast cancer cell migration and protrusion dynamics in an aligned collagen environment. Understanding the regulation of breast cancer cell migration in aligned and random 3D collagen environments will enhance the current understanding of progression to metastatic disease on a cellular level. Citation Format: Rachel Van Doorn, Joseph Szulczewski, Suzanne Ponik. Regulating Rac1 signaling proteins influences migratory and protrusive behaviors of metastatic breast cancer cells in aligned, 3D collagen and collagen-like matrices [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 27.
Preclinical assessment of antiviral combination therapy in a genetically humanized mouse model for hepatitis delta virus infection
Authors: Benjamin Y. Winer, Elham Shirvani-Dastgerdi, Yaron Bram, Julie Sellau, Benjamin E. Low, Heath Johnson, Tiffany Huang, Gabriela Hrebikova, Brigitte Heller, Yael Sharon, Katja Giersch, Sherif Gerges, Kathleen Seneca, Mihai-Alexandru Pais, Angela S. Frankel, Luis Chiriboga, John Cullen, Ronald G. Nahass, Marc Lutgehetmann, Jared E. Toettcher, Michael V. Wiles, Robert E. Schwartz, Alexander Ploss
Journal: Science Translational Medicine (2018)

An inbred mouse model for HDV infection can be used to study virally induced immune responses and for testing antiviral therapeutics.
Regulatory challenges of nanomedicines and their follow-on versions: A generic or similar approach?
Authors: Stefan Mühlebach
Journal: Advanced Drug Delivery Reviews (2018)

Nanomedicines and follow-on versions (also called nanosimilars in the EU) have been on the market partially for decades although without recognition of their nano properties in the beginning; a substantial number is in clinical development. Nanomedicines are typically synthetic and belong to the non-biological complex drugs. They show a high variability in form, structure, and size. Additionally large molecule biologics show nano-characteristics meaning nano-dimension in size (1–100 nm) or specific properties related to these dimensions. The high complexity of nanomedicines with their heterogeneous structures do not allow a full physicochemical quality characterization, challenging the regulatory evaluation especially for follow-on versions upon comparison with the reference product. The generic paradigm with the sameness approach for quality and bioequivalence in blood plasma is not appropriate for nanomedicines where a similar approach is needed. After experiencing non-equivalence of authorized parenteral colloidal iron follow-on versions, EMA and FDA issued reflection papers and draft guidances for industry to present their current thinking on the evaluation of such complex products. A stepwise approach to evaluate the extent of similarity, from quality, including critical quality attributes (CQA) and assessment of nano properties, to a non-clinical biodistribution assay, required in the the EU but not in the US, and to clinical evaluation makes sense. The cumulated totality of evidence for the authorization of nanomedicine follow-on versions goes case-by-case. Interchangeability, or substitutability, is a challenge. However, a defined or even harmonized approval pathway for these follow-versions is still missing and causes potential differences in approval. To progress, a science-based discussion platform among stakeholders and experts in the field is necessary. An agenda has been agreed [5], namely CQA assessment, publication of scientific and clinical findings, consensus on nomenclature and labelling, and regulatory actions on substandard complex drug products. Consensus created in a public private approach will support progress towards a defined and harmonized regulatory pathway for nanomedicines and their follow-on versions. This will provide drug innovation but also larger access to follow-on versions of nanomedicines, both a benefit for the patient.
Efficacy and safety of continuing versus withdrawing adalimumab therapy in maintaining remission in patients with non-radiographic axial spondyloarthritis (ABILITY-3): a multicentre, randomised, double-blind study
Authors: Robert Landewé, Joachim Sieper, Philip Mease, Robert D Inman, Robert G Lambert, Atul Deodhar, Helena Marzo-Ortega, Marina Magrey, Uta Kiltz, Xin Wang, Mei Li, Sheng Zhong, Nael M Mostafa, Apinya Lertratanakul, Aileen L Pangan, Jaclyn K Anderson
Journal: The Lancet (2018)
The human naive B cell repertoire contains distinct subclasses for a germline-targeting HIV-1 vaccine immunogen
Authors: Colin Havenar-Daughton, Anita Sarkar, Daniel W. Kulp, Laura Toy, Xiaozhen Hu, Isaiah Deresa, Oleksandr Kalyuzhniy, Kirti Kaushik, Amit A. Upadhyay, Sergey Menis, Elise Landais, Liwei Cao, Jolene K. Diedrich, Sonu Kumar, Torben Schiffner, Samantha M. Reiss, Grégory Seumois, John R. Yates, James C. Paulson, Steven E. Bosinger, Ian A. Wilson, William R. Schief, Shane Crotty
Journal: Science Translational Medicine (2018)

Inspection of the naive B cell repertoire specific for an HIV vaccine immunogen provides actionable information for human vaccine design and advancement.
Cross-Modality Comparisons Between Radiofrequency Ablation and Stereotactic Body Radiotherapy for Treatment of Hepatocellular Carcinoma: Limitations of the National Cancer Database
Authors: Jeffrey R. Olsen, James D. Murphy, Christopher L. Hallemeier, Smith Apisarnthanarax, Florence Huguet, Salma K. Jabbour
Journal: Journal of Clinical Oncology (2018)
Right Lower Quadrant Pain With Melena
Authors: Natasha DeNicola, Fadi Attiyeh
Journal: JAMA Surgery (2018)

A woman in her early 50s with a history of polycystic ovarian syndrome, diabetes, stroke, and coronary artery disease presented to the emergency department with 12 hours of sudden-onset, constant, right lower quadrant abdominal pain associated with vomiting and melena. What is your diagnosis?
Bladder Extirpation vs Preservation
Authors: David B. Cahn, Elizabeth A. Handorf, Marc C. Smaldone
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
Platelet-RBC interaction mediated by FasL/FasR induces procoagulant activity important for thrombosis
Authors: Christoph Klatt, Irena Krüger, Saskia Zey, Kim-Jürgen Krott, Martina Spelleken, Nina Sarah Gowert, Alexander Oberhuber, Lena Pfaff, Wiebke Lückstädt, Kerstin Jurk, Martin Schaller, Hadi Al-Hasani, Jürgen Schrader, Steffen Massberg, Konstantin Stark, Hubert Schelzig, Malte Kelm, Margitta Elvers
Journal: Journal of Clinical Investigation (2018)

Red blood cells (RBCs) influence rheology, and release ADP, ATP, and nitric oxide, suggesting a role for RBCs in hemostasis and thrombosis. Here, we provide evidence for a significant contribution of RBCs to thrombus formation. Anemic mice showed enhanced occlusion times upon injury of the carotid artery. A small population of RBCs was located to platelet thrombi and enhanced platelet activation by a direct cell contact via the FasL/FasR (CD95) pathway known to induce apoptosis. Activation of platelets in the presence of RBCs led to platelet FasL exposure that activated FasR on RBCs responsible for externalization of phosphatidylserine (PS) on the RBC membrane. Inhibition or genetic deletion of either FasL or FasR resulted in reduced PS exposure of RBCs and platelets, decreased thrombin generation, and reduced thrombus formation in vitro and protection against arterial thrombosis in vivo. Direct cell contacts between platelets and RBCs via FasL/FasR were shown after ligation of the inferior vena cava (IVC) and in surgical specimens of patients after thrombectomy. In a flow restriction model of the IVC, reduced thrombus formation was observed in FasL-/- mice. Taken together, our data reveal a significant contribution of RBCs to thrombosis by the FasL/FasR pathway.
Hospital-at-Home Care Programs—Is the Hospital of the Future at Home?
Authors: Joshua M. Liao, Amol Navathe, Matthew J. Press
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
Retraction notice to "Overcoming antibiotic resistance: Is siderophore Trojan horse conjugation an answer to evolving resistance in microbial pathogens?" [Journal of Controlled Release, Volume 269, 10 January 2018, Pages 63-87]
Authors: Kalyani Dhusia, Archana Bajpai, P.W. Ramteke
Journal: Journal of Controlled Release (2018)
Questionable Assumptions Provided in Nonoperative Treatment of Appendicitis Survey
Authors: David A. Talan
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
Firearm Injuries and Violence Prevention — The Potential Power of a Surgeon General’s Report
Authors: John Maa, Ara Darzi
Journal: New England Journal of Medicine (2018)

Firearm Injuries and Violence Prevention Increases in the frequency and lethality of mass shootings argue for efforts to reframe the debate about guns as a public health issue. A powerful step would be a Surgeon General’s report to characterize the problem of firearm injuries and violence in the United States.
The Carbohydrate-Insulin Model of Obesity
Authors: David S. Ludwig, Cara B. Ebbeling
Journal: JAMA Internal Medicine (2018)

Despite intensive research, the causes of the obesity epidemic remain incompletely understood and conventional calorie-restricted diets continue to lack long-term efficacy. According to the carbohydrate-insulin model (CIM) of obesity, recent increases in the consumption of processed, high-glycemic-load carbohydrates produce hormonal changes that promote calorie deposition in adipose tissue, exacerbate hunger, and lower energy expenditure. Basic and genetic research provides mechanistic evidence in support of the CIM. In animals, dietary composition has been clearly demonstrated to affect metabolism and body composition, independently of calorie intake, consistent with CIM predictions. Meta-analyses of behavioral trials report greater weight loss with reduced-glycemic load vs low-fat diets, though these studies characteristically suffer from poor long-term compliance. Feeding studies have lacked the rigor and duration to test the CIM, but the longest such studies tend to show metabolic advantages for low-glycemic load vs low-fat diets. Beyond the type and amount of carbohydrate consumed, the CIM provides a conceptual framework for understanding how many dietary and nondietary exposures might alter hormones, metabolism, and adipocyte biology in ways that could predispose to obesity. Pending definitive studies, the principles of a low-glycemic load diet offer a practical alternative to the conventional focus on dietary fat and calorie restriction.
Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) in cancer
Authors: Xinwei Huang, Hong Zhang, Xiaoran Guo, Zongxin Zhu, Haibo Cai, Xiangyang Kong
Journal: Journal of Hematology & Oncology (2018)

The insulin-like growth factor-2 mRNA-binding protein 1 (IGF2BP1) plays essential roles in embryogenesis and carcinogenesis. IGF2BP1 serves as a post-transcriptional fine-tuner regulating the expression of some essential mRNA targets required for the control of tumor cell proliferation and growth, invasion, and chemo-resistance, associating with a poor overall survival and metastasis in various types of human cancers. Therefore, IGF2BP1 has been traditionally regarded as an oncogene and potential therapeutic target for cancers. Nevertheless, a few studies have also demonstrated its tumor-suppressive role. However, the details about the contradictory functions of IGF2BP1 are unclear. The growing numbers of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have been identified as its direct regulators, during tumor cell proliferation, growth, and invasion in multiple cancers. Thus, the mechanisms of post-transcriptional modulation of gene expression mediated by IGF2BP1, miRNAs, and lncRNAs in determining the fate of the development of tissues and organs, as well as tumorigenesis, need to be elucidated. In this review, we summarized the tissue distribution, expression, and roles of IGF2BP1 in embryogenesis and tumorigenesis, and focused on modulation of the interconnectivity between IGF2BP1 and its targeted mRNAs or non-coding RNAs (ncRNAs). The potential use of inhibitors of IGF2BP1 and its related pathways in cancer therapy was also discussed.
Second-generation antipsychotic drugs and short-term mortality: a systematic review and meta-analysis of placebo-controlled randomised controlled trials
Authors: Johannes Schneider-Thoma, Orestis Efthimiou, Maximilian Huhn, Marc Krause, Leonie Reichelt, Hannah Röder, John M Davis, Georgia Salanti, Stefan Leucht
Journal: The Lancet Psychiatry (2018)