tbuckley/cabot-search huggingface dataset:
Binding of Free and Immune Complex‐Associated Hepatitis C Virus to Erythrocytes Is Mediated by the Complement System
Authors: Kazi Abdus Salam, Richard Y. Wang, Teresa Grandinetti, Valeria De Giorgi, Harvey J. Alter, Robert D. Allison
Journal: Hepatology (2018)

Erythrocytes bind circulating immune complexes (ICs) and facilitate IC clearance from the circulation. Chronic hepatitis C virus (HCV) infection is associated with IC‐related disorders. In this study, we investigated the kinetics and mechanism of HCV and HCV‐IC binding to and dissociation from erythrocytes. Cell culture‐produced HCV was mixed with erythrocytes from healthy blood donors, and erythrocyte‐associated virus particles were quantified. Purified complement proteins, complement‐depleted serum, and complement receptor antibodies were used to investigate complement‐mediated HCV‐erythrocyte binding. Purified HCV‐specific immunoglobulin G (IgG) from a chronic HCV‐infected patient was used to study complement‐mediated HCV‐IC/erythrocyte binding. Binding of HCV to erythrocytes increased 200‐ to 1,000‐fold after adding complement active human serum in the absence of antibody. Opsonization of free HCV occurred within 10 minutes, and peak binding to erythrocytes was observed at 20‐30 minutes. Complement protein C1 was required for binding, whereas C2, C3, and C4 significantly enhanced binding. Complement receptor 1 (CR1, CD35) antibodies blocked the binding of HCV to erythrocytes isolated from chronically infected HCV patients and healthy blood donors. HCV‐ICs significantly enhanced complement‐mediated binding to erythrocytes compared to unbound HCV. Dissociation of complement‐opsonized HCV from erythrocytes depended on the presence of Factor I. HCV released by Factor I bound preferentially to CD19 + B cells compared to other leukocytes. Conclusion: These results demonstrate that complement mediates the binding of free and IC‐associated HCV to CR1 on erythrocytes and provide a mechanistic rationale for investigating the differential phenotypic expression of HCV‐IC–related disease.
Annals Story Slam - Perspectives and Urgency
Authors: Yasmina Arroyo-Jimenez
Journal: Annals of Internal Medicine (2018)

Web Exclusives17 April 2018Annals Story Slam - Perspectives and UrgencyFREEYasmina Arroyo-Jimenez, MDYasmina Arroyo-Jimenez, MDSIU Medicine, Springfield, Illinois (Y.A.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W18-0009 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - Perspectives and Urgency "Perspectives and Urgency," by Dr. Yasmina Arroyo-Jimenez (Duration 5:06)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: SIU Medicine, Springfield, Illinois (Y.A.)Corresponding Author: Yasmina Arroyo-Jimenez, MD; e-mail, [email protected]edu. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 17 April 2018Volume 168, Issue 8Page: SS1 ePublished: 17 April 2018 Issue Published: 17 April 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.Loading ...
Alloreactive fetal T cells promote uterine contractility in preterm labor via IFN-γ and TNF-α
Authors: Michela Frascoli, Lacy Coniglio, Russell Witt, Cerine Jeanty, Shannon Fleck-Derderian, Dana E. Myers, Tzong-Hae Lee, Sheila Keating, Michael P. Busch, Philip J. Norris, Qizhi Tang, Giovanna Cruz, Lisa F. Barcellos, Nardhy Gomez-Lopez, Roberto Romero, Tippi C. MacKenzie
Journal: Science Translational Medicine (2018)

Human fetal T cell activation against maternal antigens could promote uterine contractions in preterm labor.
Dunce Phosphodiesterase Acts as a Checkpoint for Drosophila Long-Term Memory in a Pair of Serotonergic Neurons
Authors: Lisa Scheunemann, Pierre-Yves Plaçais, Yann Dromard, Martin Schwärzel, Thomas Preat
Journal: Neuron (2018)

A key function of the brain is to filter essential information and store it in the form of stable, long-term memory (LTM). We demonstrate here that the Dunce (Dnc) phosphodiesterase, an important enzyme that degrades cAMP, acts as a molecular switch that controls LTM formation in Drosophila. We show that, during LTM formation, Dnc is inhibited in the SPN, a pair of newly characterized serotonergic neurons, which stimulates the cAMP/PKA pathway. As a consequence, the SPN activates downstream dopaminergic neurons, opening the gate for LTM formation in the olfactory memory center, the mushroom body. Strikingly, transient inhibition of Dnc in the SPN by RNAi was sufficient to induce LTM formation with a training protocol that normally generates only short-lived memory. Thus, Dnc activity in the SPN acts as a memory checkpoint to guarantee that only the most relevant learned experiences are consolidated into stable memory.
Exploring low mood in a person with cancer
Authors: Alexandra Pitman, Sahil Suleman, Nicholas Hyde, Andrew Hodgkiss
Journal: BMJ (2018)

### What you need to know A 54 year old man asks his doctor for a sleeping tablet. He has recently been diagnosed with a Dukes B adenocarcinoma of the rectum and seems low in mood. Although he has been given a good prognosis, has completed neoadjuvant chemotherapy, and is booked for curative surgery shortly, he expresses doubts that he will live much longer. His doctor wonders if he might be depressed or anxious, and how best to address this. Depression and anxiety are more common in patients with cancer, and they are associated with poorer quality of life and cancer survival.12 This article offers advice on how to recognise these disorders, and when to offer referral for specialist advice. During the assessment, form an impression about whether the patient has depression: ### History Explore current mood and difficulties with sleep. Facilitate disclosure by acknowledging that some patients may feel depressed or anxious after a cancer diagnosis, even when receiving lifesaving treatment.
Correlation between toxicity and outcome after multimodality therapy of locoregionally advanced (LRA) adenocarcinoma (ACA) of the esophagus (E) and gastroesophageal junction (GEJ).
Authors: Kwabena Osei-Boateng, Lisa A. Rybicki, Thomas W. Rice, Cristina P. Rodriguez, Gregory M.M. Videtic, Jerrold P. Saxton, Michael J. McNamara, Denise I. Ives, Joanna Bodmann, David J. Adelstein
Journal: Journal of Clinical Oncology (2012)

e14611 Background: Multiagent concurrent chemoradiation (CRT) and surgery is a standard curative-intent approach for patients (pts) with LRA ACA of the E/GEJ. This single institution retrospective analysis examined whether toxicities occurring during induction chemoradiation (ICRT) were independently prognostic for outcome. Methods: Between 11/99 and 7/06, 152 pts with T3, N1 or M1a ACA of the E/GEJ were entered onto one of two Cleveland Clinic trials. ICRT with 96 hour infusions of cisplatin (20mg/m 2 /d) and fluorouracil (1000mg/m 2 /d) beginning on day 1 of radiation (30Gy@1.5Gy bid), was followed by surgery and identical post-operative CRT. 75 pts also received 2 years of oral gefitinib. Multivariable Cox analysis was used to identify prognostic factors for overall survival (OS), freedom from recurrence (FFR), locoregional (LRC) and distant metastatic control (DMC). Both clinical features (including demographics, tumor characteristics, symptomatic and pathologic response), and ICRT- related toxicities (including nausea/vomiting, mucositis/dysphagia, neutropenia, thrombocytopenia, neutropenic fever and any unplanned hospitalization) were analyzed. Results: Of the 152 pts enrolled, resection proved possible in 138 (91%). With a median follow-up of 90 (range 57-126) months, the 5-year Kaplan-Meier projected OS is 22%, FFR 24%, DMC 27% and LRC 69%. As expected, in multivariable analysis, earlier clinical stage disease and a pathologic and symptomatic response to ICRT all proved favorable for treatment outcomes. In addition, the development of grade 3-4 (vs. grade 0-2) mucositis and/or dysphagia during ICRT was a significant risk factor for distant recurrence [HR 2.62 (1.34-5.12), p=0.005]; any recurrence [HR 2.08 (1.08-4.00), p=0.027] and death [HR 2.00 (1.07-3.74), p=0.031]. Neutropenic fever was also correlated with distant recurrence [HR 1.82 (1.03-3.22, p=0.039] and any recurrence [HR 2.19 (1.23-3.90) p=0.007]. Conclusions: Neutropenic fever and the development of grade 3-4 mucositis and/or dysphagia during ICRT are independently associated with worse outcomes after multimodality therapy for E/GEJ ACA.
Blood-based biomarkers for the diagnosis and monitoring of gliomas
Authors: Marcus A Zachariah, Joao Paulo Oliveira-Costa, Bob S Carter, Shannon L Stott, Brian V Nahed
Journal: Neuro-Oncology (2018)

Monitoring patient response to treatment is challenging for most cancers, but it is particularly difficult in glioblastoma multiform, the most common and aggressive form of malignant brain tumor. These tumors exhibit a high degree of heterogeneity which may not be reflected in a biopsy. To determine if the current standard of care is effective, glioma patients are monitored using MRI or CT scans, an effective but sometimes misleading approach due to the phenomenon of pseudoprogression. As such, there is incredible need for a minimally invasive "liquid biopsy" to assist in molecularly characterizing the tumors while also aiding in the identification of true progression in glioblastoma. This review details the status and potential impact for circulating tumor cells, extracellular vesicles, ctDNA, and ctRNA, putative circulating biomarkers found in the blood in glioblastoma patients. As mutation-based therapy becomes more prevalent in gliomas, blood-based analyses may offer a non-invasive method of identifying mutations. The ability to obtain serial "liquid biopsies" will provide unique opportunities to study the evolution of tumors and mechanisms of treatment resistance and monitor for mutational changes in response to therapy.
Interfering with local fibrotic platelet activation significantly inhibits fibrosis in multiple animal models: suggestions of the importance of the platelet-wound healing axis for fibrosis
Authors: K. Stuart, H. Kabra, S. Jalgaonkar, T. Skurnac, A. Woolley, N. Snead, N. Bachtell, D. Leeming, M. Karsdal, J. Paderi
Journal: Journal of Hepatology (2018)
Health Insurance for Asian Americans, Native Hawaiians, and Pacific Islanders Under the Affordable Care Act
Authors: John J. Park, Sarah Humble, Benjamin D. Sommers, Graham A. Colditz, Arnold M. Epstein, Howard K. Koh
Journal: JAMA Internal Medicine (2018)

This cohort study analyzed the extent of post–Affordable Care Act (ACA) health insurance coverage gains for Asian Americans, Native Hawaiians, and Pacific Islanders and whether disparities in coverage have narrowed over time.
High SVR rates in patients with and without cirrhosis treated in real life with Sofosbuvir/Velpatasvir (SOF/VEL) combination for 12 weeks without Ribavirin (RBV)
Authors: A. Mangia, V. Piazzolla, R. Losappio, M. Mazzola, E. Visaggi, D. Bacca, F. Sogari, D. Potenza, R. Santoro, I. Carraturo, V. Tagarielli, G. Lauletta, A. Giannelli, A. Gesualdo, N. Minerva
Journal: Journal of Hepatology (2018)
Getting to Dry
Authors: Sandip Zalawadiya, Lynne Warner Stevenson
Journal: Circulation (2018)

Getting to DryArticle, see p 1671 H eart failure (HF) hospitalization presents a substantial burden to patients, hospitals, and payors.Hospitals face competing incentives from government payors because prolonged lengths of stay risk unreimbursed costs beyond the fixed reimbursement, whereas premature discharge increases the risk of 30-day readmission, for which hospitals can be penalized on a much broader scale.Clinicians have struggled to define the objective criteria regarding readiness for discharge from a HF hospitalization, which should address not only relief of congestion, but also evaluation of etiology, enhancement of guideline-directed therapies, review of disease trajectory, and consolidation of outpatient management.Once gaps in the transition process have been closed, the major cause of readmission is recurrent congestion.Regardless of how congestion is documented, 1-3 patients who go home "wet" are likely to return "wetter".Quality improvement and cost containment efforts are converging to design care pathways that begin early during hospitalization to ensure adequate decongestion by discharge.
Hyperkalemia influences the outcome of patients with cirrhosis with acute decompensation (AD) and acute on chronic liver failure (ACLF)
Authors: G. Mezzano, A. Cardenas, F. Aguilar, M. Pavesi, C. Sole, E. Solà, L. Napoleone, I. Graupera, A. Juanola, M. Carol, G. De Prada, N. Fabrellas, J. Martinez, F. Saliba, T. Welzel, V. Arroyo, P. Ginès
Journal: Journal of Hepatology (2018)
使用杜匹鲁单抗和伴随局部皮质类固醇(LIBERTY AD CHRONOS)对中度至重度异位性皮炎的长期治疗:一项严格评价
Authors: J. Thomson, A.G.H. Wernham, H.C. Williams
Journal: British Journal of Dermatology (2018)

Summary 异位性皮炎(AD)是一种常见的慢性炎症性皮肤病。主要的治疗方法是每天涂抹保湿剂和抗炎霜,通常是局部用皮质类固醇(TCS)。严重病例中使用的免疫抑制药物会引起副作用(不良副作用)。去年,《柳叶刀》上发表了一项针对AD的全新免疫抑制疗法的试验,称为杜匹鲁单抗。在本文中,来自英国诺丁汉的皮肤科医生严格评价了该研究。该项研究由业界赞助,检查了杜匹鲁单抗的长期疗效和安全性,这种”生物”药物会选择性地抑制AD中涉及的免疫细胞。这项随机、双盲、安慰剂对照试验在全球161个诊所中开展。每周(319名患者)或每两周(106名患者)为中度至重度AD成人患者注射300mg杜匹鲁单抗,共注射52周。所有患者(包括315名接受安慰剂的患者)均根据需要继续使用TCS。研究人员发现,杜匹鲁单抗+ TCS的耐受性良好(意思是,患者能够持续治疗)并且对AD的改善情况要好于单独使用TCS,但会引起更多的副作用(尤其是结膜炎)。而每周和每两周注射的疗法在疗效上未报告任何差异。这在总体上是一项组织妥善的研究,但评论家对此有所保留。还需要招募更多的参与者才能进行合理的统计:也就是”播种”,需要广泛的测试才能精通并信任该药物。评论家的再分析表明,每两周剂量比每周剂量更加有效,而费用只有后者的一半。大部分参与者患有中度AD,但生物制剂通常是为重度病患准备的。应将该药物与另一种系统性免疫抑制剂相比较,而非安慰剂。这些因素可能使结论倾向于该药物。
Announcing the Teachable Moment Editorial Fellowship
Authors: Deborah Grady
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
Prevalence and Correlates of Prescription Stimulant Use, Misuse, Use Disorders, and Motivations for Misuse Among Adults in the United States
Authors: Wilson M. Compton, Beth Han, Carlos Blanco, Kimberly Johnson, Christopher M. Jones
Journal: American Journal of Psychiatry (2018)

The authors sought to simultaneously examine the prevalence and correlates of prescription stimulant use, misuse, use disorders, and motivations for misuse in the U.S. adult population.This was a nationally representative household population study of adults age 18 or older from the 2015 and 2016 National Surveys on Drug Use and Health (N=102,000). Measurements included prescription stimulant use, use without misuse, misuse without use disorders, and misuse with use disorders, as well as sociodemographic characteristics, health conditions, and mental health factors.Among U.S. adults, 6.6% (annual average) used prescription stimulants overall; 4.5% used without misuse, 1.9% misused without use disorders, and 0.2% had use disorders. Adults with past-year prescription stimulant use disorders did not differ from those with misuse without use disorders in any of the examined sociodemographic characteristics and in many of the examined substance use problems. The most commonly reported motivations for misuse were to help be alert or concentrate (56.3%). The most likely source of misused prescription stimulants was by obtaining them free from friends or relatives (56.9%). More frequent prescription stimulant misuse and use disorder were associated with an increased likelihood of obtaining medications from physicians or from drug dealers or strangers and less likelihood of obtaining them from friends or relatives.Approximately 16.0 million U.S. adults used prescription stimulants in the preceding year (annual average), 5.0 million misused prescription stimulants, and 0.4 million had use disorders. Cognitive enhancement was the most commonly reported reason for misusing prescription stimulants. Patients who are using their medication for cognitive enhancement or diverting their medication to others present a high risk.
P283The precursor Pro-Adrenomedullin is an active protein: it supports cardiomyocyte survival and regulates cardiac inflammation related to myocardial infarction
Authors: S Hinrichs, S Scherschel, J T Neumann, M Schwarzl, Y Yan, K Klingel, S Blankenberg, C Meyer, D Westermann, D Lindner
Journal: Cardiovascular Research (2018)
Upregulation of miR-34c driven by JNK and FOXO3 in livers expressing mutant Z alpha1-antitrypsin
Authors: P. Piccolo, A. Barbato, F. Borel, P. Annunziata, S. Attanasio, R. Ferriero, A. Carissimo, S. Campione, L. Quagliata, L.M. Terracciano, J. Teckman, C. Mueller, N. Brunetti-Pierri
Journal: Journal of Hepatology (2018)
Malignant Arrhythmia in a 40-Year-Old Man
Authors: Yap-Hang Chan, Jo Jo Hai, Hung-Fat Tse
Journal: JAMA Cardiology (2018)

A 40-year-old man who smoked with a self-described heart valve problem and several days of flulike symptoms presented to the emergency department with acute onset of palpitations and diaphoresis. What would you do next?
Rejecting Reality and Substituting One?'s Own; Why Bioethics Should Be Concerned With Medically Unexplained Symptoms
Authors: Mark Henderson Arnold, Ian Kerridge
Journal: The American Journal of Bioethics (2018)

“The MUS field is a conflictual space, where polemical styles of engagement inform the expectations of many healthcare professionals and sufferers alike” (Greco 2012, 2,368).Allopathic, traditional...
Preoperative right heart hemodynamics predict postoperative acute kidney injury after heart transplantation
Authors: Goksel Guven, Milos Brankovic, Alina A. Constantinescu, Jasper J. Brugts, Dennis A. Hesselink, Sakir Akin, Ard Struijs, Ozcan Birim, Can Ince, Olivier C. Manintveld, Kadir Caliskan
Journal: Intensive Care Medicine (2018)

Acute kidney injury (AKI) frequently occurs after heart transplantation (HTx), but its relation to preoperative right heart hemodynamic (RHH) parameters remains unknown. Therefore, we aimed to determine their predictive properties for postoperative AKI severity within 30 days after HTx. From 1984 to 2016, all consecutive HTx recipients (n = 595) in our tertiary referral center were included and analyzed for the occurrence of postoperative AKI staged by the kidney disease improving global outcome criteria. The effects of preoperative RHH parameters on postoperative AKI were calculated using logistic regression, and predictive accuracy was assessed using integrated discrimination improvement (IDI), net reclassification improvement (NRI), and area under the receiver operating characteristic curves (AUC). Postoperative AKI occurred in 430 (72%) patients including 278 (47%) stage 1, 66 (11%) stage 2, and 86 (14%) stage 3 cases. Renal replacement therapy (RRT) was administered in 41 (7%) patients. Patients with higher AKI stages had also higher baseline right atrial pressure (RAP; median 7, 7, 8, and in RRT 11 mmHg, p trend = 0.021), RAP-to-pulmonary capillary wedge pressure ratio (median 0.37, 0.36, 0.40, 0.47, p trend = 0.009), and lower pulmonary artery pulsatility index (PAPi) values (median 2.83, 3.17, 2.54, 2.31, p trend = 0.012). Higher RAP and lower PAPi values independently predicted AKI severity [adjusted odds ratio (OR) per doubling of RAP 1.16 (1.02–1.32), p = 0.029; of PAPi 0.85 (0.75–0.96), p = 0.008]. Based on IDI, NRI, and delta AUC, inclusion of these parameters improved the models' predictive accuracy. Preoperative PAPi and RAP strongly predict the development of AKI early after HTx and can be used as early AKI predictors.
Factors implicated in the risk of developing hepatocellular carcinoma (HCC) in patients with cirrhosis due to HCV Implications of Sustained Virological Response (SVR)
Authors: A. Castaño, A. Gomez, M. Torner, M. Fraile, C. Álvarez-Navascués, V. Cadahía-Rodrigo, M.L.G. Dieguez, M. Varela, M. Rodríguez
Journal: Journal of Hepatology (2018)
<i>PTEN</i> deletion in luminal cells of mature prostate induces replication stress and senescence in vivo
Authors: Maxime Parisotto, Elise Grelet, Rana El Bizri, Yongyuan Dai, Julie Terzic, Doriane Eckert, Laetitia Gargowitsch, Jean-Marc Bornert, Daniel Metzger
Journal: The Journal of Experimental Medicine (2018)

Genetic ablation of the tumor suppressor PTEN in prostatic epithelial cells (PECs) induces cell senescence. However, unlike oncogene-induced senescence, no hyperproliferation phase and no signs of DNA damage response (DDR) were observed in PTEN-deficient PECs; PTEN loss-induced senescence (PICS) was reported to be a novel type of cellular senescence. Our study reveals that PTEN ablation in prostatic luminal epithelial cells of adult mice stimulates PEC proliferation, followed by a progressive growth arrest with characteristics of cell senescence. Importantly, we also show that proliferating PTEN-deficient PECs undergo replication stress and mount a DDR leading to p53 stabilization, which is however delayed by Mdm2-mediated p53 down-regulation. Thus, even though PTEN-deficiency induces cellular senescence that restrains tumor progression, as it involves replication stress, strategies promoting PTEN loss–induced senescence are at risk for cancer prevention and therapy.
Epidemiology, predictors and outcomes of multi drug resistant bacterial infections in patients with cirrhosis across the world. Final results of the “Global study”
Authors: S. Piano, V. Singh, P. Caraceni, R. Maiwall, C. Alessandria, J. Fernandez, E. Soares, D.J. Kim, S.E. Kim, M. Marino, J. Vorobioff, R. de Cassia Ribeiro Barea, M. Merli, L. Elkrief, V.M.V. Blasco, A. Krag, S. Singh, L.A. Lesmana, C. Toledo, S. Marciano, V. Xavier, F. Wong, N. Intagliata, L. Rabinowich, L.A. Colombato, S.G. Kim, A. Gerbes, F. Durand, J.P. Roblero, K. Bhamidimarri, T.D. Boyer, M. Maevskaya, E.L. Fassio, H.S. Kim, J.-S. Hwang, A. Gadano, S.K. Sarin, P. Angeli
Journal: Journal of Hepatology (2018)
NLRP3 inflammasome activation in hepatocytes results in pyroptotic cell death, release of NLRP3 particles and liver fibrosis
Authors: S. Schuster, F.A. Guerra, C.D. Johnson, C.J. Calvente, D. Povero, A. Eguchi, M.D. Mcgeough, H.M. Hoffman, P. Pelegrin, A. Feldstein
Journal: Journal of Hepatology (2018)