tbuckley/cabot-search huggingface dataset:
FRI0510 Increased expression of v-domain ig suppressor of t-cell activation (VISTA) on leukocytes of granulomatosis with polyangiitis (GPA) patients
Authors: R. Hid Cadena, J. Yuan, M.G. Huitema, A.M. Boots, C. Stegeman, E. Brouwer, A. Rutgers, P. Heeringa, W.H. Abdulahad
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Vascular inflammation in GPA is the result from an inflammatory event combined with a highly specific immune response. Antineutrophil cytoplasmic antibodies (ANCA) specific for GPA are directed against neutrophil granule proteins. Neutrophils are known to play an important role in the pathogenesis of GPA. Under normal conditions, activation of immune cells is positively and negatively regulated by stimulatory and inhibitory checkpoint molecules. The right balance between the expression of both molecules is crucial in fine-tuning the immune response and preventing autoimmunity. Recently, VISTA (V-domain Ig suppressor of T cell activation) has been identified as a potent negative regulator of T cell activation. <h3>Objectives</h3> This study aimed to investigate the expression of VISTA on circulating leukocytes of GPA-patients and compare it with vasculitis control (VC) patients with Giant Cell Arteritis (GCA) and healthy controls (HC). <h3>Methods</h3> In a cross-sectional study, fresh blood samples were obtained from 43 GPA-patients in remission on immunosuppressive treatment, 24 VC and 34 sex and age-matched HC. The frequency of VISTA expression was determined on Th-cells (CD45RO<sup>-</sup> and CD45RO<sup>+</sup>), NK cells, monocyte subsets (classical/non classical/intermediate) and on neutrophils (suppressive/non suppressive subsets) by flow cytometry. <h3>Results</h3> The proportion of VISTA expressing Th-cells was significantly increased in GPA-patients compared with HCs, this increase could be seen in both, the CD45RO<sup>-</sup> compartment as well as in the CD45RO<sup>+</sup> compartment. NK cells from GPA-patients showed an increase in the proportion of VISTA expressing cells when compared to the VCs and HCs. Among monocyte subsets, a slight decrease in the proportion of VISTA on the Intermediate subset could be seen. Interestingly, on neutrophils a significant increase in the proportion of VISTA<sup>+</sup> cells was seen in GPA-patients in comparison to HCs and VCs. This increase was most pronounced in the suppressive neutrophil subset. <h3>Conclusions</h3> VISTA expression is increased in both naïve and memory Th cells of GPA patients in remission. Interestingly, neutrophils of GPA patients showed higher levels of VISTA and this was most pronounced in the suppressive neutrophil subset. Whether the increased expression of VISTA has functional consequences needs further investigation. <h3>Disclosure of Interest</h3> None declared
The proteome microenvironment determines the protective effect of preconditioning in cisplatin-induced acute kidney injury
Authors: Martin R. Späth, Malte P. Bartram, Nicolàs Palacio-Escat, K. Johanna R. Hoyer, Cedric Debes, Fatih Demir, Christina B. Schroeter, Amrei M. Mandel, Franziska Grundmann, Giuliano Ciarimboli, Andreas Beyer, Jayachandran N. Kizhakkedathu, Susanne Brodesser, Heike Göbel, Jan U. Becker, Thomas Benzing, Bernhard Schermer, Martin Höhne, Volker Burst, Julio Saez-Rodriguez, Pitter F. Huesgen, Roman-Ulrich Müller, Markus M. Rinschen
Journal: Kidney International (2018)
Preparing Surrogates for Complex Decision Making
Authors: Rebecca L. Sudore
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
Dual-Modality ImmunoPET/Fluorescence Imaging of Prostate Cancer with an Anti-PSCA Cys-Minibody
Authors: Wenting K Tsai, Kirstin A Zettlitz, Richard Tavaré, Naoko Kobayashi, Robert E Reiter, Anna M Wu
Journal: Theranostics (2018)

Inadequate diagnostic methods for prostate cancer lead to over-and undertreatment, and the inability to intraoperatively visualize positive margins may limit the success of surgical resection.Prostate cancer visualization could be improved by combining the complementary modalities of immuno-positron emission tomography (immunoPET) for preoperative disease detection, and fluorescence imaging-guided surgery (FIGS) for real-time intraoperative tumor margin identification.Here, we report on the evaluation of dual-labeled humanized anti-prostate stem cell antigen (PSCA) cys-minibody (A11 cMb) for immunoPET/fluorescence imaging in subcutaneous and orthotopic prostate cancer models.Methods: A11 cMb was site-specifically conjugated with the near-infrared fluorophore Cy5.5 and radiolabeled with 124 I or 89 Zr. 124 I-A11 cMb-Cy5.5 was used for successive immunoPET/fluorescence imaging of prostate cancer xenografts expressing high or moderate levels of PSCA (22Rv1-PSCA and PC3-PSCA). 89Zr-A11 cMb-Cy5.5 dual-modality imaging was evaluated in an orthotopic model.Ex vivo biodistribution at 24 h was used to confirm the uptake values, and tumors were visualized by post-mortem fluorescence imaging.Results: A11 cMb-Cy5.5 retained low nanomolar affinity for PSCA-positive cells.Conjugation conditions were established (dye-to-protein ratio of 0.7:1) that did not affect the biodistribution, pharmacokinetics, or clearance of A11 cMb.ImmunoPET using dual-labeled 124 I-A11 cMb-Cy5.5 showed specific targeting to both 22Rv1-PSCA and PC3-PSCA s.c.xenografts in nude mice.Ex vivo biodistribution confirmed specific uptake to PSCA-expressing tumors with 22Rv1-PSCA:22Rv1 and PC3-PSCA:PC3 ratios of 13:1 and 5.6:1, respectively.Consistent with the immunoPET, fluorescence imaging showed a strong signal from both 22Rv1-PSCA and PC3-PSCA tumors compared with non-PSCA expressing tumors.In an orthotopic model, 89 Zr-A11 cMb-Cy5.5 immunoPET was able to detect intraprostatically implanted 22Rv1-PSCA cells.Importantly, fluorescence imaging clearly distinguished the prostate tumor from surrounding seminal vesicles.Conclusion: Dual-labeled A11 cMb specifically visualized PSCA-positive tumor by successive immunoPET/fluorescence, which can potentially be translated for preoperative whole-body prostate cancer detection and intraoperative surgical guidance in patients.
Abstract 17878: Calmodulin Mutation (CALM-F90L) Associated With Familial Idiopathic Ventricular Fibrillation Disrupts L-type Ca Channel Inactivation and Activates Sarcoplasmic Reticulum Ca Release in Ventricular Myocytes
Authors: Dmytro Kryshtal, Hyun S Hwang, Christopher Johnson, Walter Chazin, Alfred L George, Bjorn Knollmann
Journal: Circulation (2014)

Introduction: The F90L mutation in calmodulin (CaM) has been associated with a familial form of autosomal-dominant idiopathic ventricular fibrillation (IVF) with features of exercise-induced QT prolongation, but the underlying arrhythmia mechanism is unknown. We previously found that CaM mutations that cause sudden death due to catecholaminergic polymorphic ventricular tachycardia (CPVT) activate ryanodine receptor (RyR2) Ca release channels; whereas CaM mutations associated with long QT syndrome (LQTS) have no effects on RyR2 channels but prolong the cardiac action potential by impairing L-type Ca current inactivation. Objective: To determine the effect of F90L mutant CaM on Ca binding affinity, L-type Ca currents and Ca handling and compare them to CaM mutants associated with CPVT (CPVT-CaM) and LQTS (LQTS-CaM). Methods and Results: We prepared recombinant wild-type (WT) and mutant CaM proteins associated with CPVT (N54I), LQTS (D96V, D130G, F142L) and IVF (F90L). Similar to LQTS CaMs, the F90L IVF mutation drastically reduced Ca binding affinity of CaM C-lobe (7-fold reduction compared to WT-CaM), whereas CPVT N54I has no effect. In voltage-clamped mouse ventricular myocytes dialyzed either with WT or mutant CaM, IVF-CaM F90L significantly impaired L-type Ca channel inactivation, similar to the effect of LQTS-CaMs, whereas CPVT-CaM had no effect (Fig. A, **p&lt;0.01 vs WT). Next, mutant CaMs effects on sarcoplasmic reticulum Ca release were tested in permeabilized ventricular myocytes. At physiological free CaM [100 nM] and Ca [120 nM], IVF-CaM F90L increased spontaneous Ca wave activity analogous to CPVT-CaM N54I, but of significantly smaller effect size (Fig. B). In contrast, LQTS-CaMs had either no effect or reduced Ca waves (Fig. B). Conclusion: The F90L CaM mutation shares characteristics with both CPVT and LQTS CaMs, which may help explain clinical features of modest exercise-induced QT prolongation and sudden arrhythmic death in patient carriers.
High-Density Lipoprotein–Targeted Therapies—Not Dead Yet—Reply
Authors: Stephen J. Nicholls, Rishi Puri, Steven E. Nissen
Journal: JAMA Cardiology (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 Cardiology 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 Cardiology journal
Cascaded Electrochemiluminescence Signal Amplifier for the Detection of Telomerase Activity from Tumor Cells and Tissues
Authors: Zhaoyan Zhao, Qingqin Tan, Xiaoxia Zhan, Jingyan Lin, Zhijin Fan, Keng Xiao, Bing Li, Yuhui Liao, Xi Huang
Journal: Theranostics (2018)

Telomerase is closely linked to the physiological transformation of tumor cells and is commonly overexpressed in most types of tumor cells.Therefore, telomerase has become a potential biomarker for the process of tumorigenesis, progression, prognosis and metastasis.Thus, it is important to develop a simple, accurate and reliable method for detecting telomerase activity.As a high signal-to-noise ratio mode, electrochemiluminescence (ECL) has been widely applied in the field of biomedical analysis.Here, our objective was to construct an improved ECL signal amplifier for the detection of telomerase activity.Methods: A cascaded ECL signal amplifier was constructed to detect telomerase activity with high selectivity via controllable construction of a lysine-based dendric Ru(bpy) 3 2+ polymer (DRP).The sensitivity, specificity and performance index were simultaneously evaluated by standard substance and cell and tissue samples.Results: With this cascaded ECL signal amplifier, high sensitivities of 100, 50, and 100 cells for three tumor cell lines (A549, MCF7 and HepG2 cell lines) were simultaneously achieved, and desirable specificity was also obtained.Furthermore, the excellent performance of this platform was also demonstrated in the detection of telomerase in tumor cells and tissues.Conclusion: This cascaded ECL signal amplifier has the potential to be a technological innovation in the field of telomerase activity detection.
Association of Elective and Emergency Cesarean Delivery With Early Childhood Overweight at 12 Months of Age
Authors: Meijin Cai, See Ling Loy, Kok Hian Tan, Keith M. Godfrey, Peter D. Gluckman, Yap-Seng Chong, Lynette Pei-Chi Shek, Yin Bun Cheung, Ngee Lek, Yung Seng Lee, Shiao-Yng Chan, Jerry Kok Yen Chan, Fabian Yap, Seng Bin Ang
Journal: JAMA Network Open (2018)

Global cesarean delivery (CD) rates have more than doubled over the past 2 decades, with an increasing contribution from elective CDs. Cesarean delivery has been linked to early childhood overweight and obesity, but limited studies have examined elective and emergency CDs separately.To investigate whether elective or emergency CD was associated with risk of early childhood overweight.Data were drawn from the Growing Up in Singapore Toward Healthy Outcomes (GUSTO) study, an ongoing prospective mother-child birth cohort study. Participants were pregnant women aged 18 years or older with homogeneous parental ethnic background in their first trimester recruited between June 2009 and September 2010 (n = 1237) at 2 major public hospitals in Singapore. Those with type 1 diabetes or undergoing chemotherapy or psychotropic drug treatment were excluded. Data analysis commenced in October 2017.Delivery mode obtained from clinical records. Elective and emergency CD examined separately against vaginal delivery as reference.Body mass index-for-age z scores at age 12 months calculated based on 2006 World Health Organization Child Growth Standards from infant weight and recumbent crown-heel length measurements taken between December 2010 and April 2012. High body mass index status at risk of overweight was defined as a z score of more than 1 SD and less than or equal to 2 SDs. Overweight was defined as a z score of more than 2 SDs.Among 727 infants analyzed (51.2% [372] male), 30.5% (222) were born via CD, of which 33.3% (74) were elective. Prevalence of at risk of overweight and overweight at age 12 months was 12.2% (89) and 2.3% (17), respectively. Elective CD was significantly associated with at risk of overweight or overweight at age 12 months after adjusting for maternal ethnicity, age, education, parity, body mass index, antenatal smoking, hypertensive disorders of pregnancy, gestational diabetes, and sex-adjusted birth weight-for-gestational age (odds ratio, 2.05; 95% CI, 1.08-3.90; P = .03). The association persisted after further adjustment for intrapartum antibiotics and first 6 months infant feeding, 2 potential mediators of early childhood overweight and obesity (odds ratio, 2.02; 95% CI, 1.05-3.89; P = .04). No significant associations were found for emergency CD. Analysis with multiple imputation for missing covariates yielded similar results.Choice of delivery mode may influence risk of early childhood overweight. Clinicians are encouraged to discuss potential long-term implications of elective CD on child metabolic outcomes with patients who intend to have children.
Association Between Polycystic Ovary Syndrome and Cancer Risk
Authors: Weiyao Yin, Henrik Falconer, Li Yin, Liangzhi Xu, Weimin Ye
Journal: JAMA Oncology (2018)

Association Between Polycystic Ovary Syndrome and Cancer RiskInconsistent results have been reported for the association between polycystic ovary syndrome (PCOS) and risks of ovarian and breast cancers. 1 Few studies had sufficient sample sizes, well-defined diagnostic criteria, or reasonable confounding adjustment. 1,2Even fewer studies have addressed the risks of other cancers.Thus, we conducted a large, population-based cohort study with a long follow-up period and rather sufficient confounding adjustment.
Novel spheroid reservoir bioartificial liver improves survival of nonhuman primates in a toxin-induced model of acute liver failure
Authors: Yi Li, Qiong Wu, Yujia Wang, Chengxin Weng, Yuting He, Mengyu Gao, Guang Yang, Li Li, Fei Chen, Yujun Shi, Bruce P. Amiot, Scott L. Nyberg, Ji Bao, Hong Bu
Journal: Theranostics (2018)

This study aims to evaluate the effectiveness and safety of the spheroid reservoir bioartificial liver (SRBAL) with porcine hepatocyte organoids in a preclinical nonhuman primate model of acute liver failure (ALF).Methods: Thirty healthy rhesus monkeys were infused with α-amanitin and lipopolysaccharide and randomized into five groups (ALF alone control group; sham no-cell SRBAL treatment group; groups A, B and C with SRBAL treatment started at 12 h, 24 h and 36 h after induction of ALF, respectively).Animals were continuously treated with the SRBAL device for 6 h and followed for up to 336 h.Results: Survival of ALF monkeys improved with hepatocyte SRBAL treatment compared to control groups.Blood ammonia and total bilirubin were lower, and albumin levels were higher in all hepatocyte SRBAL treatment groups.No evidence of porcine endogenous retrovirus was identified in monkey liver or blood after SRBAL treatment.Titers of monkey antibody (IgG, IgM) did not rise after SRBAL treatment.In survival cases, the proportion of necrotic and apoptotic hepatocytes was lower in SRBAL-treated groups, with earlier liver regeneration leading to recovery.Cytokines TNF-α, IL-6, IL-12, IL-1β, IL-8, IFN-γ and IL-2 were ameliorated by the SRBAL treatment, while levels of M-CSF; HGF, EGF and VEGF; IL-1RA and MIF rose on priming, proliferation and the late phase of liver regeneration.Conclusions: The benefit of SRBAL therapy included preventive effects and therapeutic effects.SRBAL improved survival rate and prolonged median survival time in a nonhuman primate model of drug-induced ALF, and these benefits declined with a delay in the initiation of therapy.Improved survival and recovery of ALF monkeys was associated with a reduction in blood ammonia levels, inhibition of the pro-inflammatory response of ALF, and provided a microenvironment more suitable for regeneration of the injured liver.
Long-Term Efficacy and Safety from the Copanlisib CHRONOS-1 Study in Patients with Relapsed or Refractory Indolent B-Cell Lymphoma
Authors: Martin Dreyling, Armando Santoro, Luigina Mollica, Sirpa Leppä, George A Follows, Georg Lenz, Won Seog Kim, Arnon Nagler, Panayiotis Panayiotidis, Judit Demeter, Muhit Özcan, Marina Kosinova, Krimo Bouabdallah, Franck Morschhauser, Don Stevens, David Trevarthen, Liana Rodrigues, Florian Hiemeyer, MingLu Wang, Jose Garcia-Vargas, Barrett H. Childs, Pier Luigi Zinzani
Journal: Blood (2018)
Switching endocrine therapy in breast cancer as a strategy for musculoskeletal symptoms, tolerance, and adherence.
Authors: Albina Kibirova, Samantha Hall, Abdul Miah, Mohamad Adham Salkeni
Journal: Journal of Clinical Oncology (2018)

192 Background: Adverse effects of endocrine therapy (ET), especially musculoskeletal symptoms (MSS), represent the major cause of treatment discontinuation in breast cancer (BC) patients, resulting in increased risk of recurrence. Aromatase inhibitors (AI), the mainstay of ET, are associated with a high incidence of MSS such as arthralgia and myalgia. The hypothesis of whether switching ET subclass improves adherence and symptoms was tested. Methods: We conducted a retrospective single site chart review of female patients with nonmetastatic BC, who were seen at Cancer Clinic from January to June of 2017. All patients received AI as a first choice of adjuvant ET; those with disease recurrence while on ET were excluded. We collected data on baseline health, adherence and discontinuation rate, as well as whether switching to a different ET agent (another AI or tamoxifen) was attempted. The subsequent compliance and symptomatology after switching were assessed. Results: 483 eligible patients were identified and divided into 4 groups based upon adherence: 354 (73.3%) were found to be compliant with AI without interruption, 109 (22.5%) switched to a different ET and remained compliant (≥ 1 switch), 16 (3.3%) eventually discontinued ET despite attempting ≥ 1 switch, and 5 patients (1.0%) stopped treatment without a switch. On comparison of the different groups, patients who permanently discontinued ET were more likely to be elderly and have preexisting musculoskeletal condition. MSS was found to be the single most common cause for AI intolerance (105 patients, 81.4%). The median time to switch was 6.3 months (0.3-63.9). Among the compliant switchers, most needed only 1 switch (79) but there were patients who required 2 or 3 switches (23 and 6, respectively). Majority of patients switched from anastrozole to exemestane (84, 51.8%). Significant improvement in symptoms after the switch was reported by 73.3% of patients. Conclusions: Switching between different ET subclasses is an effective treatment strategy to alleviate side effects and enhance adherence to ET. A higher compliance rate of 95.8% was observed in our study compared to a national average estimated at &lt; 80%.
Antagonism of Glycolysis and Reductive Carboxylation of Glutamine Potentiates Activity of Oncolytic Adenoviruses in Cancer Cells
Authors: Arthur Dyer, Benjamin Schoeps, Sally Frost, Philip Jakeman, Eleanor M. Scott, Joshua Freedman, Egon J. Jacobus, Leonard W. Seymour
Journal: Cancer Research (2018)

Abstract Tumor cells exhibiting the Warburg effect rely on aerobic glycolysis for ATP production and have a notable addiction to anaplerotic use of glutamine for macromolecular synthesis. This strategy maximizes cellular biosynthetic potential while avoiding excessive depletion of NAD+ and provides an attractive anabolic environment for viral infection. Here, we evaluate infection of highly permissive and poorly permissive cancer cells with wild-type adenoviruses and the oncolytic chimeric adenovirus enadenotucirev (EnAd). All adenoviruses caused an increase in glucose and glutamine uptake along with increased lactic acid secretion. Counterintuitively, restricting glycolysis using 2-deoxyglucose or by limiting glucose supply strongly improved virus activity in both cell types. Antagonism of glycolysis also boosted EnAd replication and transgene expression within human tumor biopsies and in xenografted tumors in vivo. In contrast, the virus life cycle was critically dependent on exogenous glutamine. Virus activity in glutamine-free cells was rescued with exogenous membrane-permeable α-ketoglutarate, but not pyruvate or oxaloacetate, suggesting an important role for reductive carboxylation in glutamine usage, perhaps for production of biosynthetic intermediates. This overlap between the metabolic phenotypes of adenovirus infection and transformed tumor cells may provide insight into how oncolytic adenoviruses exploit metabolic transformation to augment their selectivity for cancer cells. Significance: This study describes changes in glucose and glutamine metabolism induced by oncolytic and wild-type adenoviruses in cancer cells, which will be important to consider in the preclinical evaluation of oncolytic viruses.