tbuckley/cabot-search huggingface dataset:
Abstract 13449: Cd40 Contributes to Renal Fibrosis in Experimental Renal Ischemia
Authors: Steven T Haller, David A Folt, Sivarajan Kumarasamy, Siddhi Upadhyaya, Joseph I Shapiro, Bina Joe, Christopher J Cooper
Journal: Circulation (2015)

Introduction: Cd40 has been implicated in renal injury following activation by its ligand (sCD40L), which is released from activated platelets. Previously we have shown that patients with renal ischemia have elevated levels of sCD40L and circulating levels of CD40 predict changes in renal function. We created a novel Cd40 mutant on the background of the genetically hypertensive Dahl S rat (S rat), which is prone to the development of renal disease, in order to determine the role of Cd40 in ischemic renal disease. Hypothesis: Cd40 induces renal fibrosis in renal ischemia. Methods: A novel Cd40 mutant, with targeted disruption of Cd40, was created in the S rat using the zinc-finger nuclease method. Male Cd40 mutant rats weighing between 250-300 g were used (n=8). Eight S rats were used as age-matched controls. Western blot analysis, trichrome staining, and immunohistochemistry were performed on kidney tissue derived from Cd40 mutants and S rats four weeks following two-kidney one clip (2K1C) surgery. Renal function was determined by urinary protein excretion (UPE), and creatinine measurements. Results: The Cd40 mutants when compared to S rats exhibited significantly lower systolic blood pressure four weeks following 2K1C surgery (130 ± 6 vs. 155 ± 4 mmHg, p&lt;0.01). Kidney tissue derived from the clipped ischemic kidneys showed a substantial decrease in fibrosis in the Cd40 mutants compared to S rat controls as assessed by trichrome staining (p&lt;0.01), which was confirmed by collagen-1 expression. The Cd40 mutants also exhibited a significant decrease in UPE (173.2 ± 18.8 vs. 230.6 ± 17.4 mg/24hrs, p&lt;0.05) and creatinine (0.85 ± 0.03 vs. 1.00 ± 0.06 mg/dL, p&lt;0.05) compared to S rat controls. Conclusions: Mutation of the Cd40 gene decreases renal fibrosis and improves renal function following renal ischemia. Our results indicate that Cd40 contributes to ischemic renal fibrosis and provides a mechanistic rationale for the development of renal dysfunction in ischemic renal disease.
Abstract 18773: Coronary Heart Disease in Premature Sudden Cardiac Death: An Autopsy Study of Asian Population
Authors: Wasawat Vutthikraivit, Prapaipan Putthapiban, Weera Sukhumthammarat, Pattara Rattanawong, Possawat Vutthikraivit, Kamonchanok Jongyota, Awapa Prombandankul, Smith Srisont
Journal: Circulation (2017)

Background: The clinical significance of coronary heart disease (CHD) as a potential cause of premature sudden cardiac death (SCD) has been reported. However, true prevalence of CHD in premature SC...
Annals Story Slam - Say Nothing
Authors: Sarah Andersen
Journal: Annals of Internal Medicine (2018)

Web Exclusives4 December 2018Annals Story Slam - Say NothingFREESarah Andersen, MDSarah Andersen, MDUniversity of Toronto, Toronto, Ontario, Canada (S.A.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W18-0035 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - Say Nothing "Say Nothing," by Sarah Andersen, MD (Duration 5:39)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: University of Toronto, Toronto, Ontario, Canada (S.A.)Current Author Address: Sarah Andersen, MD; e-mail, sarah.[email protected]com. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 4 December 2018Volume 169, Issue 11Page: SS1 ePublished: 4 December 2018 Issue Published: 4 December 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.Loading ...
Checkpoint Blockade Therapy May Sensitize Aggressive and Indolent Non-Hodgkin Lymphoma to Subsequent Therapy
Authors: Nicole A Carreau, Orrin Pail, Philippe Armand, Reid W Merryman, Ranjana H Advani, Michael A Spinner, Alex F. Herrera, Robert W. Chen, Sarah Tomassetti, Radhakrishnan Ramchandren, Muhammad Hamid, Sarit Assouline, Raoul Santiago, Nina D. Wagner-Johnston, Suman Paul, Jakub Svoboda, Steven M. Bair, Stefan Klaus Barta, Yang Liu, Sunita Nathan, Madelyn Burkart, Reem Karmali, Pallawi Torka, Kevin A. David, Catherine Wei, Frederick Lansigan, Lukas Emery, Daniel Persky, Sonali M. Smith, Julio C. Chavez, Yuhe Xia, Andrea B Troxel, Catherine Diefenbach
Journal: Blood (2018)
Echocardiographic Screening for Pulmonary Hypertension in Congenital Heart Disease
Authors: Konstantinos Dimopoulos, Robin Condliffe, Robert M.R. Tulloh, Paul Clift, Rafael Alonso-Gonzalez, Radwa Bedair, Natali A.Y. Chung, Gerry Coghlan, Samantha Fitzsimmons, Alessandra Frigiola, Luke S. Howard, Petra Jenkins, Damien Kenny, Wei Li, Simon T. MacDonald, Colm McCabe, James J. Oliver, Mark S. Spence, Gergely V. Szantho, Kate von Klemperer, Dirk G. Wilson, Stephen J. Wort
Journal: Journal of the American College of Cardiology (2018)

Echocardiography is the mainstay in screening for pulmonary hypertension (PH). International guidelines suggest echocardiographic parameters for suspecting PH, but these may not apply to many adults with congenital heart disease (ACHD). PH is relatively common in ACHD patients and can significantly affect their exercise capacity, quality of life, and prognosis. Identification of patients who have developed PH and who may benefit from further investigations (including cardiac catheterization) and treatment is thus extremely important. A systematic review and survey of experts from the United Kingdom and Ireland were performed to assess current knowledge and practice on echocardiographic screening for PH in ACHD. This paper presents the findings of the review and expert statements on the optimal approaches when using echocardiography to assess ACHD patients for PH, with particular focus on major subgroups: patients with right ventricular outflow tract obstruction, patients with systemic right ventricles, patients with unrepaired univentricular circulation, and patients with tetralogy of Fallot with pulmonary atresia.
The NAD+ Salvage Pathway Potently Stimulates Hematopoiesis through Increased Mitochondrial Clearance and Asymmetric Division
Authors: Nicola Vannini, Vasco Campos, Mukul Girotra, Shanti Rojas-Sutterlin, Josefine Tratwal, Simone Ragusa, Evangelos Stefanidis, Dongryeol Ryu, Pernille Y. Rainer, Gennady Nikitin, Sonja Giger, Yang Li Terytty, Aikateirini Semilietof, Aurelien L. Oggier, Yannick Yersin, Loïc Tauzin, Eija Pirinen, Wan-Chen Cheng, Joanna Ratajczak, Carles Canto, Martin Ehrbar, Federico Sizzano, Tatiana V. Petrova, Dominique Vanhecke, Aimable Nahimana, Michel A. Duchosal, Ping-Chih Ho, Bart Deplancke, George Coukos, Matthias P. Lutolf, Olaia Naveiras
Journal: Blood (2018)
Abstract 15529: Aspirin and Renal Insufficiency Progression in Patients With Atrial Fibrillation and Chronic Kidney Disease
Authors: Daniele Pastori, Pasquale Pignatelli, Francesco Perticone, Angela Sciacqua, Roberto Carnevale, Alessio Farcomeni, Stefania Basili, Gino R Corazza, Giovanni Davì, Gregory Lip, Francesco Violi
Journal: Circulation (2015)

Introduction: Thromboxane (Tx)A2 is an eicosanoid with aggregating and vasoconstrictor properties. In experimental models, TxA2 reduces renal perfusion and accelerates renal failure, but its role in human pathophysiology is unclear. Hypothesis: To test the association between the use of aspirin, which inhibits TxA2 production, and the incidence of an estimated Glomerular Filtration Rate (eGFR) &lt;60 and &lt;45 ml/min/1.73 m2 in a long-term follow-up. Methods: Prospective multicentre observational cohort study including 800 atrial fibrillation (AF) patients affected by chronic kidney disease (CKD) from I Clinica Medica of “Sapienza” University of Rome, from University Magna Græcia of Catanzaro, and from the ARAPACIS study. CKD was defined as an eGFR &lt;90 ml/min/1.73 m2 by CKD-EPI formula; eGFR was calculated at baseline and after a median of 28.0 months. In 401 patients, urinary 11-dehydro-TxB2 was measured. Results: Baseline median eGFR was 64.9 ml/min/1.73 m2; 147 and 91 AF patients had an incident eGFR &lt;60 and &lt;45 ml/min/1.73 m2, respectively; 16.5% AF patients were treated with aspirin (100 mg/day) in addition to oral anticoagulants. At multivariable analysis, aspirin was inversely associated with incident eGFR&lt;45 ml/min/1.73 m2 (odds ratio [OR]: 0.367, 95% confidence interval [CI] 0.153-0.880, p=0.025), but not with incident eGFR&lt;60 ml/min/1.73 m2. The effect of aspirin persisted after propensity score adjustment (OR: 0.920, 95%CI 0.857-0.988, p=0.022). Median TxB2 levels were higher in patients with (123.0 ng/mg creatinine) compared to those without incident eGFR &lt;45 ml/min/1.73 m2 (90.0, p=0.031) and significantly associated with incident eGFR&lt;45 ml/min/1.73 m2 (log TxB2 OR 2.239, 95%CI 1.056-4.747, p=0.036). TxB2 was significantly lower in aspirin-treated patients (p=0.014). Conclusions: TxA2 may be implicated in renal function deterioration in AF patients with CKD.
Mode of Delivery and Childhood Obesity
Authors: Caroline Mitchell, Jorge E. Chavarro
Journal: JAMA Network Open (2018)

Meijin Cai, BSc Hons; See Ling Loy, PhD; Kok Hian Tan, MBBS; Keith M. Godfrey, PhD; Peter D. Gluckman, FRS; Yap-Seng Chong, MD; Lynette Pei-Chi Shek, MBBS; Yin Bun Cheung, PhD; Ngee Lek, FRCPCH; Yung Seng Lee, PhD; Shiao-Yng Chan, PhD; Jerry Kok Yen Chan, PhD; Fabian Yap, FRCPCH; Seng Bin Ang, MBBS
PAX5 P80R mutation identifies a novel subtype of B-cell precursor acute lymphoblastic leukemia with favorable outcome
Authors: Marie Passet, Nicolas Boissel, François Sigaux, Colombe Saillard, Mario Bargetzi, Ibrahima Ba, Xavier Thomas, Carlos Graux, Yves Chalandon, Thibaut Leguay, Etienne Lengliné, Johanna Konopacki, Samuel Quentin, Eric Delabesse, Marina Lafage-Pochitaloff, Cédric Pastoret, Nathalie Grardel, Vahid Asnafi, Véronique Lhéritier, Jean Soulier, Hervé Dombret, Emmanuelle Clappier
Journal: Blood (2018)
Double Autologous Stem Cell Transplantation Significantly Prolongs Progression-Free Survival and Overall Survival in Comparison with Single Autotransplantation in Newly Diagnosed Multiple Myeloma: An Analysis of Phase 3 EMN02/HO95 Study
Authors: Michele Cavo, Francesca Patriarca, Elena Zamagni, Vittorio Montefusco, Luca Dozza, Monica Galli, Sara Bringhen, Nicoletta Testoni, Mariella Grasso, Stelvio Ballanti, Paola Tacchetti, Giampietro Semenzato, Anna Marina Liberati, Giulia Benevolo, Mauro Spriano, Paolo Di Bartolomeo, Tommaso Caravita di Toritto, Angelo D. Palmas, Anna Maria Cafro, Fortunato Morabito, Pellegrino Musto, Rita Rizzi, Antonio Palumbo, Pieter Sonneveld
Journal: Blood (2017)
FRI0247 Gout characteristics and its association with the presence of cardiovascular disease: a case-control study
Authors: S.J. Lopez Salguero, M. Andrés Collado
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Gout is an independent risk factor for any type of cardiovascular disease (CVD). The exact mechanism behind remains to be elucidated, but persistent crystal-related inflammation is presumed as a key factor. <h3>Objectives</h3> The aim of this study was to assess whether gout characteristics that may indicate a more severe disease and higher inflammatory load are associated with the presence of CVD. <h3>Methods</h3> Case-control study, performed at baseline of an inception cohort including consecutive crystal-proven gout patients seen at a rheumatology unit. Gout features (time since first attack, number of attacks, number of joints affected, pattern of presentation, tophi) were registered after interview and physical exam. Presence and duration of CVD (which included coronary heart disease, heart failure, stroke or peripheral artery disease) was registered after interview and records review. Those patients who have suffered from CVD prior to the onset of gout were excluded. Other cardiovascular risk factors, as well as clinical and laboratory variables, were also registered. Odds ratios with 95% confidence intervals (95% CI) for each gout feature were calculated between patients with and without CVD, using a multiple logistic regression model to adjust for confounders. <h3>Results</h3> The inception cohort includes 308 patients; 54 were excluded for this study because gout onset occurred after CVD, so finally 254 cases were analysed. Mean age was 61.4 years (SD 13.9), being 225 (88.6%) men. Regarding gout, median duration was 5 years (IQR 1–12), median number of reported attacks was 5 (IQR 2–14) that had involved a median of 3 joints (IQR 2–5); presenting attack was monoarticular in 77.4% cases, oligoarticular in 16.7%, and polyarticular in 6%, and 58 patients (22.8%) showed tophi at enrolment. A total of 32 patients (12.6%) had suffered from CVD at enrolment. Table 1 shows the results of logistic regression analysis: time since first attack and polyarticular presentation of gout both significantly associated with the presence of CVD, while other variables showed no association. After multivariate analysis, time since first attack persisted associated with CVD, while polyarticular involvement showed a trend towards signification. <h3>Conclusions</h3> Time since first attack and likely a polyarticular presentation, two variables that may estimate crystal and inflammatory load in gout patients, are independently associated with the presence of CVD, adding evidence to the role of persistent inflammation on its development. <h3>Disclosure of Interest</h3> None declared
FDA recommends “modernizing” review of devices in wake of global investigation
Authors: Jeanne Lenzer
Journal: BMJ (2018)

The US Food and Drug Administration is making changes to how medical devices are cleared for sale after a scathing investigation into the industry.

The global investigation into the medical device industry by journalists from 36 countries, including The BMJ , BBC Panorama , and the Guardian and led by the International Consortium of Investigative Journalists, unearthed thousands of documents to reveal rising numbers of malfunctions and injuries.1

Scott Gottlieb, FDA commissioner, and Jeff Shuren, director of the Center of Devices and Radiological Health, said in a statement that there would be changes to the 510(k) …
Ensuring Fairness in Machine Learning to Advance Health Equity
Authors: Alvin Rajkomar, Michaela Hardt, Michael D. Howell, Greg Corrado, Marshall H. Chin
Journal: Annals of Internal Medicine (2018)

Machine learning is used increasingly in clinical care to improve diagnosis, treatment selection, and health system efficiency. Because machine-learning models learn from historically collected data, populations that have experienced human and structural biases in the past-called protected groups-are vulnerable to harm by incorrect predictions or withholding of resources. This article describes how model design, biases in data, and the interactions of model predictions with clinicians and patients may exacerbate health care disparities. Rather than simply guarding against these harms passively, machine-learning systems should be used proactively to advance health equity. For that goal to be achieved, principles of distributive justice must be incorporated into model design, deployment, and evaluation. The article describes several technical implementations of distributive justice-specifically those that ensure equality in patient outcomes, performance, and resource allocation-and guides clinicians as to when they should prioritize each principle. Machine learning is providing increasingly sophisticated decision support and population-level monitoring, and it should encode principles of justice to ensure that models benefit all patients.
Defining linkage to care following human immunodeficiency virus (HIV) diagnosis for public health monitoring in Europe
Authors: Sara Croxford, Dorthe Raben, Stine F Jakobsen, Fiona Burns, Andrew Copas, Alison E Brown, Valerie C Delpech
Journal: Eurosurveillance (2018)

Prompt linkage to human immunodeficiency virus (HIV) care after diagnosis is crucial to ensure optimal patient outcomes. However, few countries monitor this important public health marker and different definitions have been applied, making country and study comparisons difficult. This article presents an expert-agreed, standard definition of linkage to care for a pragmatic approach to public health monitoring, appropriate to the European context. Here, linkage to care is defined as patient entry into specialist HIV care after diagnosis, measured as the time between the HIV diagnosis date and one of the following markers: either the first clinic attendance date, first CD4+ cell count or viral load date, or HIV treatment start date, depending on data availability; Linkage is considered prompt if within 3 months of diagnosis. Application of this definition by researchers and public health professionals when reporting surveillance or research data relating to linkage to care after HIV diagnosis will enable reliable comparisons across countries, better assessment of the success of health services programmes aimed at improving peoples access to HIV treatment and care and the identification of barriers limiting access to HIV care across Europe.
The Double-Hit Gene Expression Signature Defines a Clinically and Biologically Distinct Subgroup within GCB-DLBCL
Authors: Daisuke Ennishi, Aixiang Jiang, Merrill Boyle, Brett Collinge, Bruno M. Grande, Susana Ben-Neriah, Graham W Slack, Pedro Farinha, Diego Villa, Anja Mottok, Barbara Meissner, Saeed Saberi, Ali Bashashati, Kerry J Savage, Laurie H Sehn, Robert Kridel, Marco A. Marra, Sohrab P Shah, Christian Steidl, Joseph M. Connors, Randy D. Gascoyne, Ryan D. Morin, David W. Scott
Journal: Blood (2018)
Use of liraglutide and risk of major cardiovascular events: a register-based cohort study in Denmark and Sweden
Authors: Henrik Svanström, Peter Ueda, Mads Melbye, Björn Eliasson, Ann-Marie Svensson, Stefan Franzén, Soffia Gudbjörnsdottir, Kristian Hveem, Christian Jonasson, Björn Pasternak
Journal: The Lancet Diabetes & Endocrinology (2018)
Detection of Individual Prostate Cancer Foci via Multiparametric Magnetic Resonance Imaging
Authors: David C. Johnson, Steven S. Raman, Sohrab A. Mirak, Lorna Kwan, Amirhossein M. Bajgiran, William Hsu, Cleo K. Maehara, Preeti Ahuja, Izak Faiena, Aydin Pooli, Amirali Salmasi, Anthony Sisk, Ely R. Felker, David S.K. Lu, Robert E. Reiter
Journal: European Urology (2018)
Abstract 15652: Gender Difference in Use of Acute Coronary Syndrome Medications and Outcomes at 6-months Post Discharge
Authors: Karice K Hyun, Emily Atkins, Clara Chow, Jens Kilian, Rohan Rajaratnam, David Brieger
Journal: Circulation (2017)

Introduction: Previous studies have shown that women with acute coronary syndrome (ACS) are less likely to receive in-hospital care such as revascularisation procedures and guideline-recommended medications. So, our aim was to find if the rate of medication use and outcomes also differ by gender in patients with ACS after discharge. Hypothesis: Women are less likely to take secondary prevention medication and have more major adverse cardiovascular events (MACE) and death than men. Methods: Of ACS patients recruited from 41 hospitals between February 2009 to September 2016, 7303 were discharged alive and followed up at 6-month post discharge as part of the Cooperative National Registry of Acute Coronary Care, Guideline Adherence and Clinical Events (CONCORDANCE) registry. Multivariable logistic regressions within the framework of generalized estimating equations were used to compare the rate of medication use, MACE (myocardial infarction, heart failure or stroke) and all-cause death within 6 months after d...
Cortical and trabecular bone microarchitecture as an independent predictor of incident fracture risk in older women and men in the Bone Microarchitecture International Consortium (BoMIC): a prospective study
Authors: Elizabeth J Samelson, Kerry E Broe, Hanfei Xu, Laiji Yang, Steven Boyd, Emmanuel Biver, Pawel Szulc, Jonathan Adachi, Shreyasee Amin, Elizabeth Atkinson, Claudie Berger, Lauren Burt, Roland Chapurlat, Thierry Chevalley, Serge Ferrari, David Goltzman, David A Hanley, Marian T Hannan, Sundeep Khosla, Ching-Ti Liu, Mattias Lorentzon, Dan Mellstrom, Blandine Merle, Maria Nethander, René Rizzoli, Elisabeth Sornay-Rendu, Bert Van Rietbergen, Daniel Sundh, Andy Kin On Wong, Claes Ohlsson, Serkalem Demissie, Douglas P Kiel, Mary L Bouxsein
Journal: The Lancet Diabetes & Endocrinology (2018)
Loss of PTEN expression induces NF-kB via PI3K/Akt pathway involving resistance to chemotherapy in acute lymphoblastic leukemia cell lines
Authors: Rong Jiang, Lubing Gu, Harry Findley, Muxiang Zhou
Journal: Cancer Research (2004)

5530   PTEN is a tumor suppressor gene responsible for downregulating the phosphoinositide 3-kinase (PI3k)/Akt pathway. Loss of PTEN expression frequently occurs in human cancer leading to high Akt activation, which consequently confers neoplastic cell survival and resistance to chemotherapy-induced apoptosis. Here we report a mechanism by which loss of PTEN expression activates the transcription factor NF-kB through the PI3k/Akt pathway that induces activation of the IkBα kinase (IKK). Activation of NF-kB by loss of PTEN expression results in resistance to doxorubicin in acute lymphoblastic leukemia (ALL) cells. Initially, we examined six leukemia cell lines derived from children with ALL for the expression of PTEN and activation of NF-kB, and found that 3 of the 6 lines lacked PTEN expression (PTEN-) and expressed constitutive activation of NF-kB. In contrast, 3 PTEN positive (PTEN+) lines were defect of NF-kB activation. Treatment of PTEN- line with PI3k kinase inhibitor Ly294002 caused downregulation of Akt activity accompanied by reduced activation of IKK and inhibition of nuclear translocation of the p65 subunit of NF-kB, resulting in increased sensitivity to doxorubicin-induced apoptosis. Similar to treatment with Ly294002, transfection of the PTEN expression plasmid into the PTEN- lines attenuated constitutive activation of both Akt and NF-kB, thereby sensitizing these cells to doxorubicin. Conversely, inhibition of PTEN expression in PTEN+ lines with siRNA induced activation of NF-kB, leading to resistance to doxorubicin-induced cell death. These results suggest that both constitutive and inducible activation of NF-kB play an important role in chemotherapy resistance, and that loss of PTEN expression is at least one reason for the constitutive activation of NF-kB in ALL cells.