tbuckley/cabot-search huggingface dataset:
Platelet P-Selectin Expression Is Associated With Atherosclerotic Wall Thickness in Carotid Artery in Humans
Authors: HidenoriKoyama, TakaakiMaeno, ShinyaFukumoto, TakuhitoShoji, TakahisaYamane, HisayoYokoyama, MasanoriEmoto, TetsuoShoji, HidekiTahara, MasaakiInaba, MasayukiHino, AtsushiShioi, TakamiMiki, YoshikiNishizawa
Journal: Circulation (2003)

Background— Recent genetic animal models reveal important roles of platelet P-selectin on progression of atherosclerosis. In the present study, we examine the relation between platelet P-selectin expression and atherosclerotic parameters in 517 subjects. Methods and Results— Unrelated subjects (n=517; 235 male and 282 female), including 187 with type 2 diabetes, 184 with hypertension, and 366 with hyperlipidemia, were enrolled in the study. P-selectin expression was determined by whole-blood flow cytometry. Arterial stiffness (stiffness index β) and arterial wall thickness (intima-media thickness [IMT]) were determined by carotid ultrasound. P-selectin expression was significantly and positively correlated with carotid IMT and stiffness index β. Multiple regression analyses showed that the association of the percentage of P-selectin–positive platelets with carotid IMT was independent of other clinical factors. Moreover, the percentage of P-selectin–positive platelets was higher in subjects with carotid pl...
Rituximab primarily targets an intra-clonal BCR signaling proficient CLL subpopulation characterized by high CD20 levels
Authors: Gabriela Pavlasova, Marek Borsky, Veronika Svobodova, Jan Oppelt, Katerina Cerna, Jitka Novotna, Vaclav Seda, Miloslava Fojtova, Jiri Fajkus, Yvona Brychtova, Michael Doubek, Sarka Pospisilova, Jiri Mayer, Marek Mraz
Journal: Leukemia (2018)
A Predictive Score for Early Mortality during Induction Therapy in Newly Diagnosed Transplant-Eligible Multiple Myeloma - an Analysis from Five GMMG and HOVON Multicenter Phase III Trials
Authors: Elias K. Mai, Thomas Hielscher, Uta Bertsch, Jana Schlenzka, Hans Jurgen Salwender, Henk M. Lokhorst, Markus Munder, Bronno van der Holt, Christian Gerecke, Michael Pfreundschuh, Ulrich Duhrsen, Peter Brossart, Sonja Zweegman, Kai Neben, Jens Hillengass, Marc-Steffen S. Raab, Dirk Hose, Edo Vellenga, Maximilian Merz, Iris Breitkreutz, Anna Jauch, Marie Jose Kersten, Hans Martin, Hans-Walter Lindemann, Norma Peter, Sandra Croockewit, Igor Wolfgang Blau, Christof Scheid, Katja C. Weisel, Pieter Sonneveld, Hartmut Goldschmidt
Journal: Blood (2017)
The Neuroplastic and Therapeutic Potential of Spinal Interneurons in the Injured Spinal Cord
Authors: Lyandysha V. Zholudeva, Liang Qiang, Vitaliy Marchenko, Kimberly J. Dougherty, Shelly E. Sakiyama-Elbert, Michael A. Lane
Journal: Trends in Neurosciences (2018)
The TRPM2 channel nexus from oxidative damage to Alzheimer’s pathologies: An emerging novel intervention target for age-related dementia
Authors: Lin-Hua Jiang, Xin Li, Sharifah A. Syed Mortadza, Megan Lovatt, Wei Yang
Journal: Ageing Research Reviews (2018)

Alzheimer's disease (AD), an age-related neurodegenerative condition, is the most common cause of dementia among the elder people, but currently there is no treatment. A number of putative pathogenic events, particularly amyloid β peptide (Aβ) accumulation, are believed to be early triggers that initiate AD. However, thus far targeting Aβ generation/aggregation as the mainstay strategy of drug development has not led to effective AD-modifying therapeutics. Oxidative damage is a conspicuous feature of AD, but this remains poorly defined phenomenon and mechanistically ill understood. The TRPM2 channel has emerged as a potentially ubiquitous molecular mechanism mediating oxidative damage and thus plays a vital role in the pathogenesis and progression of diverse neurodegenerative diseases. This article will review the emerging evidence from recent studies and propose a novel 'hypothesis' that multiple TRPM2-mediated cellular and molecular mechanisms cascade Aβ and/or oxidative damage to AD pathologies. The 'hypothesis' based on these new findings discusses the prospect of considering the TRPM2 channel as a novel therapeutic target for intervening AD and age-related dementia.
Activating Transcription Factor 4 Modulates TGFβ-Induced Aggressiveness in Triple-Negative Breast Cancer via SMAD2/3/4 and mTORC2 Signaling
Authors: Adrián González-González, Esperanza Muñoz-Muela, Juan A. Marchal, Francisca E. Cara, Maria P. Molina, Marina Cruz-Lozano, Gema Jiménez, Akanksha Verma, Alberto Ramírez, Wei Qian, Wen Chen, Anthony J. Kozielski, Olivier Elemento, María D. Martín-Salvago, Rafael J. Luque, Carmen Rosa-Garrido, David Landeira, María Quintana-Romero, Roberto R. Rosato, Maria A. García, Cesar L. Ramirez-Tortosa, Hanna Kim, Cristian Rodriguez-Aguayo, Gabriel Lopez-Berestein, Anil K. Sood, Jose A. Lorente, Pedro Sánchez-Rovira, Jenny C. Chang, Sergio Granados-Principal
Journal: Clinical Cancer Research (2018)

Abstract Purpose: On the basis of the identified stress-independent cellular functions of activating transcription factor 4 (ATF4), we reported enhanced ATF4 levels in MCF10A cells treated with TGFβ1. ATF4 is overexpressed in patients with triple-negative breast cancer (TNBC), but its impact on patient survival and the underlying mechanisms remain unknown. We aimed to determine ATF4 effects on patients with breast cancer survival and TNBC aggressiveness, and the relationships between TGFβ and ATF4. Defining the signaling pathways may help us identify a cell signaling–tailored gene signature. Experimental Design: Patient survival data were determined by Kaplan–Meier analysis. Relationship between TGFβ and ATF4, their effects on aggressiveness (tumor proliferation, metastasis, and stemness), and the underlying pathways were analyzed in three TNBC cell lines and in vivo using patient-derived xenografts (PDX). Results: ATF4 overexpression correlated with TNBC patient survival decrease and a SMAD-dependent crosstalk between ATF4 and TGFβ was identified. ATF4 expression inhibition reduced migration, invasiveness, mammosphere-forming efficiency, proliferation, epithelial–mesenchymal transition, and antiapoptotic and stemness marker levels. In PDX models, ATF4 silencing decreased metastases, tumor growth, and relapse after chemotherapy. ATF4 was shown to be active downstream of SMAD2/3/4 and mTORC2, regulating TGFβ/SMAD and mTOR/RAC1–RHOA pathways independently of stress. We defined an eight-gene signature with prognostic potential, altered in 45% of 2,509 patients with breast cancer. Conclusions: ATF4 may represent a valuable prognostic biomarker and therapeutic target in patients with TNBC, and we identified a cell signaling pathway–based gene signature that may contribute to the development of combinatorial targeted therapies for breast cancer. Clin Cancer Res; 24(22); 5697–709. ©2018 AACR.
Matrix Stiffening and EGFR Cooperate to Promote the Collective Invasion of Cancer Cells
Authors: Eloise M. Grasset, Thomas Bertero, Alexandre Bozec, Jonas Friard, Isabelle Bourget, Sabrina Pisano, Margaux Lecacheur, Majdi Maiel, Caroline Bailleux, Alexander Emelyanov, Marius Ilie, Paul Hofman, Guerrino Meneguzzi, Christophe Duranton, Dmitry V. Bulavin, Cedric Gaggioli
Journal: Cancer Research (2018)

Abstract In squamous cell carcinoma (SCC), tissue invasion by collectively invading cells requires physical forces applied by tumor cells on their surrounding extracellular matrix (ECM). Cancer-related ECM is composed of thick collagen bundles organized by carcinoma-associated fibroblasts (CAF) within the tumor stroma. Here, we show that SCC cell collective invasion is driven by the matrix-dependent mechano-sensitization of EGF signaling in cancer cells. Calcium (Ca2+) was a potent intracellular second messenger that drove actomyosin contractility. Tumor-derived matrix stiffness and EGFR signaling triggered increased intracellular Ca2+ through CaV1.1 expression in SCC cells. Blocking L-type calcium channel expression or activity using Ca2+ channel blockers verapamil and diltiazem reduced SCC cell collective invasion both in vitro and in vivo. These results identify verapamil and diltiazem, two drugs long used in medical care, as novel therapeutic strategies to block the tumor-promoting activity of the tumor niche. Significance: This work demonstrates that calcium channels blockers verapamil and diltiazem inhibit mechano-sensitization of EGF-dependent cancer cell collective invasion, introducing potential clinical strategies against stromal-dependent collective invasion. Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/18/5229/F1.large.jpg. Cancer Res; 78(18); 5229–42. ©2018 AACR.
Extracorporeal organ support (ECOS) in critical illness and acute kidney injury: from native to artificial organ crosstalk
Authors: Faeq Husain-Syed, Zaccaria Ricci, Daniel Brodie, Jean-Louis Vincent, V. Marco Ranieri, Arthur S. Slutsky, Fabio Silvio Taccone, Luciano Gattinoni, Claudio Ronco
Journal: Intensive Care Medicine (2018)
Epidemiologic, clinical, and pathologic features of lymphomas at the Peruvian hospital: Hospital Nacional Cayetano Heredia.
Authors: Juan Padilla, Diego Venegas, Miro Rodriguez, Jaime Caceres, Jaime Cok, Carolina Tokumura, Wilson Ruiz, Victor Ulloa, Oswaldo Abelardo Grados Sanchez
Journal: Journal of Clinical Oncology (2012)

e12041 Background: During the decade 70’ to 90’ incidence of lymphomas in Lima, Peru increased from 3.4 to 7.5 per 100 000 females and from 6 to 8.3 per 100 000 males. We describe epidemiological, clinical and pathologic features of patients with lymphoma diagnosed at the Hospital Nacional Cayetano Heredia (HNCH), center of reference of Lima north. Methods: Retrospective study of 433 patients with lymphoma diagnosed from 1998 to 2008 at the HNCH. Results: The mean age was 44.8 years (range 1 to 93 years), the ratio was 1.5:1 for male and female respectively, 85.9% were Non Hodgkin Lymphoma (LNH). In Hodgkin diseases’ patients the mean age was 34 years and ratio male: female was 2:1; whereas, in NHL, the average age was 45.9 years and ratio male: female was 1.4:1. The more frequently symptoms were weight loss (40.5%) and lymphadenopathy (36.7%). The 55.08% were clinical stage I-II. The most frequent location was nodal (55.1%). More frequently extra nodal locations were: gastrointestinal (15.2%) and skin (10.8%). In NHL, the immunophenotype B were: B (57.8%), T (19.6%) and not determined ( 22.6%). The most common histological type was large diffuse cells lymphoma (35.8%). T-cell lymphoma adults occurs in 6.9% of cases, follicular in 4.7% and anaplastic in 4.7%.According to RECIST 1,1: 78.12% had remission completed and parcial. In Hodgkin’s disease’s treatment with ABVD was 90.97% of responses complete and parcial. During this period 23.45% of patients reported died Conclusions: Our patients with lymphoma retain the same general characteristics of the worldwide. ATLL had prevalence high relative to others series
Changing Trends in Etiology‐Based and Ethnicity‐Based Annual Mortality Rates of Cirrhosis and Hepatocellular Carcinoma in the United States
Authors: Donghee Kim, Andrew A. Li, Brandon J. Perumpail, Chiranjeevi Gadiparthi, Won Kim, George Cholankeril, Jeffrey S. Glenn, Stephen A. Harrison, Zobair M. Younossi, Aijaz Ahmed
Journal: Hepatology (2018)

With recent improvements in the treatment of end-stage liver disease (ESLD), a better understanding of the burden of cirrhosis and hepatocellular carcinoma (HCC) is needed in the United States. A population-based study using the US Census and national mortality database was performed. We identified the age-standardized etiology-specific mortality rates for cirrhosis and HCC among US adults ages 20 years or older from 2007 to 2016. We determined temporal mortality rate patterns by joinpoint analysis with estimates of annual percentage change (APC). Age-standardized cirrhosis-related mortality rates increased from 19.77/100,000 persons in 2007 to 23.67 in 2016 with an annual increase of 2.3% (95% confidence interval [CI] 2.0-2.7). The APC in mortality rates for hepatitis C virus (HCV)-cirrhosis shifted from a 2.9% increase per year during 2007 to 2014 to a 6.5% decline per year during 2014 to 2016. Meanwhile, mortality for cirrhosis from alcoholic liver disease (ALD, APC 4.5%) and NAFLD (APC 15.4%) increased over the same period, whereas mortality for hepatitis B virus (HBV)-cirrhosis decreased with an average APC of -1.1%. HCC-related mortality increased from 3.48/100,000 persons in 2007 to 4.41 in 2016 at an annual rate of 2.0% (95% CI 1.3-2.6). Etiology-specific mortality rates of HCC were largely consistent with cirrhosis-related mortality. Minority populations had a higher burden of HCC-related mortality. Conclusion: Cirrhosis-related and HCC-related mortality rates increased between 2007 and 2016 in the United States. However, mortality rates in HCV-cirrhosis demonstrated a significant decline from 2014 to 2016, during the direct-acting antiviral era. Mortality rates for ALD/NAFLD-cirrhosis and HCC have continued to increase, whereas HBV-cirrhosis-related mortality declined during the 10-year period. Importantly, minorities had a disproportionately higher burden of ESLD-related mortality.
Factors that affect patient reported outcome after anterior cruciate ligament reconstruction–a systematic review of the Scandinavian knee ligament registers
Authors: Eric Hamrin Senorski, Eleonor Svantesson, Angelo Baldari, Olufemi R Ayeni, Lars Engebretsen, Francesco Franceschi, Jón Karlsson, Kristian Samuelsson
Journal: British Journal of Sports Medicine (2018)

Objective To perform a systematic review of findings from the Scandinavian knee ligament registers with regard to factors that affect patient reported outcome after anterior cruciate ligament (ACL) reconstruction. Design Systematic review. Data sources Four electronic databases: PubMed, EMBASE, the Cochrane Library and AMED were searched, and 157 studies were identified. Two reviewers independently screened the titles, abstracts and full text articles for eligibility. A modified version of the Downs and Black checklist was applied for quality appraisal. Eligibility criteria for selecting studies Studies published from the Scandinavian registers from their establishment in 2004 and onwards that documented patient reported outcome and provided information on concomitant injuries were eligible. Results A total of 35 studies were included. Younger age at ACL reconstruction, male sex, not smoking and receiving a hamstring tendon autograft positively influenced patient reported outcome. Patients with concomitant cartilage and meniscal injuries reported inferior subjective knee function compared with patients with an isolated ACL tear. One study reported that patients treated non-reconstructively reported inferior knee function compared with patients who had ACL reconstruction. Conclusion Younger age, male sex, not smoking, receiving a hamstring tendon autograft and the absence of concomitant injuries were associated with superior patient reported outcomes after ACL reconstruction.
Antibiotic therapy–induced collateral damage: IgA takes center stage in pulmonary host defense
Authors: Juergen Lohmeyer, Rory E. Morty, Susanne Herold
Journal: Journal of Clinical Investigation (2018)

The use of broad-spectrum antibiotics in empirical antimicrobial therapy is a lifesaving strategy for patients in intensive care. At the same time, antibiotics dramatically increase the risk for nosocomial infections, such as hospital‑acquired pneumonia caused by Pseudomonas aeruginosa, and other antibiotic-resistant bacteria. In this issue of the JCI, Robak and colleagues identified a mechanism by which depletion of resident gut and lung microbiota by antibiotic treatment results in secondary IgA deficiency and impaired anti–P. aeruginosa host defense. Impaired defenses could be improved by substitution of polyclonal IgA via the intranasal route in a mouse model of pneumonia. Importantly, antibiotic treatment caused lung IgA deficiency that involved reduced TLR-dependent production of a proliferation-inducing ligand (APRIL) and B cell–activating factor (BAFF) in intensive care unit patients. These patients might therefore benefit from future strategies to increase pulmonary IgA levels.
Abstract 17497: Risk Stratification of Patients With Out of Hospital Cardiac Arrest without ST-Segment Elevation: An Initial Exploratory Risk Score-The ‘PEA’ Score
Authors: Syed W Haider, Saurav Chatterjee, Partha Sardar, Jacqueline Tamis-Holland
Journal: Circulation (2016)

Introduction:  Out-of-hospital cardiac arrest (OHCA) affects over 325,000 adults each year in the United States, with survival rates of about 10.6%. Predicting risk of mortality in patients who achieve return of spontaneous circulation (ROSC) remains a challenge. While scoring tools to predict the risk of mortality in OHCA patients exist, risk stratification specifically in the patient with OHCA and no ST elevation on ECG (NSTE) has not been explored.   Hypothesis:  A simple risk model can be used to predict in-hospital mortality in patients presenting with OHCA and NSTE.   Methods:  Patient-level data were obtained from the Nationwide Inpatient Sample (NIS) from 2008-2011. A stepwise logistic regression model with backward elimination was used to determine the contribution of all candidate covariates. We assigned risk factors identified by multivariable analysis weighted points proportional to the logarithmic transformation of the β regression coefficient values. A risk score was then calculated for each patient in the derivation cohort, and validated with patients in the validation cohort. We used Stata 12.0SE (StataCorp, College Station, TX). A P value of    Results:  A total of 97,042 patients presenting to the hospital with OHCA and NSTE were examined. Among these, 58,066 patients (59.8%) died before hospital discharge. Three independent prognostic factors were identified, and each was assigned a number of points proportional to its regression coefficient: Pulseless (non-ventricular fibrillation) arrest (1 point), Elderly (Age greater than 85 years) (1 point), and Acidosis (1 point).The c- statistic for the PEA score point system was 0.61 (95% CI 0.60-0.62, p   Conclusions:  A novel risk model can predict in-hospital mortality in patients presenting with OHCA and NSTE. This simple score can be used on initial presentation to the hospital and may help to inform healthcare teams and families regarding patients’ prognoses.
CD38-Mediated Immunosuppression as a Mechanism of Tumor Cell Escape from PD-1/PD-L1 Blockade
Authors: Limo Chen, Lixia Diao, Yongbin Yang, Xiaohui Yi, B. Leticia Rodriguez, Yanli Li, Pamela A. Villalobos, Tina Cascone, Xi Liu, Lin Tan, Philip L. Lorenzi, Anfei Huang, Qiang Zhao, Di Peng, Jared J. Fradette, David H. Peng, Christin Ungewiss, Jonathon Roybal, Pan Tong, Junna Oba, Ferdinandos Skoulidis, Weiyi Peng, Brett W. Carter, Carl M. Gay, Youhong Fan, Caleb A. Class, Jingfen Zhu, Jaime Rodriguez-Canales, Masanori Kawakami, Lauren Averett Byers, Scott E. Woodman, Vassiliki A. Papadimitrakopoulou, Ethan Dmitrovsky, Jing Wang, Stephen E. Ullrich, Ignacio I. Wistuba, John V. Heymach, F. Xiao-Feng Qin, Don L. Gibbons
Journal: Cancer Discovery (2018)

Abstract Although treatment with immune checkpoint inhibitors provides promising benefit for patients with cancer, optimal use is encumbered by high resistance rates and requires a thorough understanding of resistance mechanisms. We observed that tumors treated with PD-1/PD-L1 blocking antibodies develop resistance through the upregulation of CD38, which is induced by all-trans retinoic acid and IFNβ in the tumor microenvironment. In vitro and in vivo studies demonstrate that CD38 inhibits CD8+ T-cell function via adenosine receptor signaling and that CD38 or adenosine receptor blockade are effective strategies to overcome the resistance. Large data sets of human tumors reveal expression of CD38 in a subset of tumors with high levels of basal or treatment-induced T-cell infiltration, where immune checkpoint therapies are thought to be most effective. These findings provide a novel mechanism of acquired resistance to immune checkpoint therapy and an opportunity to expand their efficacy in cancer treatment. Significance: CD38 is a major mechanism of acquired resistance to PD-1/PD-L1 blockade, causing CD8+ T-cell suppression. Coinhibition of CD38 and PD-L1 improves antitumor immune response. Biomarker assessment in patient cohorts suggests that a combination strategy is applicable to a large percentage of patients in whom PD-1/PD-L1 blockade is currently indicated. Cancer Discov; 8(9); 1156–75. ©2018 AACR. See related commentary by Mittal et al., p. 1066. This article is highlighted in the In This Issue feature, p. 1047
Fertility doctor who “facilitated” sex selection is struck off for practising without a licence
Authors: Clare Dyer
Journal: BMJ (2018)

A leading infertility specialist who claimed that he acted not as a doctor but only as a “facilitator” for couples hoping to choose their baby’s sex has been struck off the UK medical register for practising medicine without a licence.

Paul Rainsbury, founder of the Rainsbury Clinic, gave up his licence to practise in 2014, claiming that he was only facilitating couples to have treatment in clinics abroad, in countries where sex selection is legal. The practice is illegal in the UK, but the clinic’s patients had their egg selection and embryo transfer at a foreign clinic. …
Cardiac Positron-Emission Tomography Images With an Amyloid-Specific Tracer in Familial Transthyretin-Related Systemic Amyloidosis
Authors: KatsutoshiFurukawa, Shu-ichiIkeda, NobuyukiOkamura, ManabuTashiro, NaokiTomita, ShozoFurumoto, RenIwata, KazuhikoYanai, YukitsukaKudo, HiroyukiArai
Journal: Circulation (2012)
An Adventure in Open Payments
Authors: Michael J. Barry
Journal: Annals of Internal Medicine (2018)

Letters17 July 2018An Adventure in Open PaymentsMichael J. Barry, MDMichael J. Barry, MDMassachusetts General Hospital, Boston, Massachusetts (M.J.B.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L18-0205 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Dr. Chen describes her experience with a misattributed payment on the Centers for Medicare & Medicaid Services Open Payments Web site. She agrees that the disputation process, particularly when delayed, is onerous and implies that disputing the payment is not worth it in her case.Both Drs. Chen and Ribadeneyra question the value of reporting and posting smaller payments on this Web site. Their comments raise the question of whether there should be some threshold for payments, either individually or collectively over a year, below which the information would not be reported or posted. For the year of ...Reference1. Fleischman W, Agrawal S, King M, Venkatesh AK, Krumholz HM, McKee D, et al. Association between payments from manufacturers of pharmaceuticals to physicians and regional prescribing: cross sectional ecological study. BMJ. 2016;354:i4189. [PMID: 27540015] doi:10.1136/bmj.i4189 CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Massachusetts General Hospital, Boston, Massachusetts (M.J.B.)Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M17-1911. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoLet the Sun Shine In! An Adventure in Open Payments Michael J. Barry An Adventure in Open Payments Helen Chen An Adventure in Open Payments Michael Ribadeneyra Metrics 17 July 2018Volume 169, Issue 2Page: 135-136KeywordsAnticoagulantsDisclosureFearMedicarePregnancy ePublished: 17 July 2018 Issue Published: 17 July 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...