tbuckley/cabot-search huggingface dataset:
Neutrophil: A mobile fertilizer
Authors: Lai Guan Ng
Journal: The Journal of Experimental Medicine (2018)

In this issue of JEM, Lee et al. (https://doi.org/10.1084/jem.20181170) provide evidence to show that early influx of neutrophils into omentum represents a key mechanism in establishing the premetastatic niche for the subsequent implantation of ovarian cancer cells at this site.
HIF-1α inducing exosomal microRNA-23a expression mediates the cross-talk between tubular epithelial cells and macrophages in tubulointerstitial inflammation
Authors: Zuo-Lin Li, Lin-Li Lv, Tao-Tao Tang, Bin Wang, Ye Feng, Le-Ting Zhou, Jing-Yuan Cao, Ri-Ning Tang, Min Wu, Hong Liu, Steven D. Crowley, Bi-Cheng Liu
Journal: Kidney International (2018)
CRISPR/Cas9 Knock-in HL60 Cells Closely Simulate Cellular and Functional Abnormalities of ELANE associated Neutropenia; Phenotype Rescue with MK-0339 Neutrophil Elastase Inhibitor
Authors: Vahagn Makaryan, Breanna Fletcher, Merideth L. Kelley, Masoud Nasri, Julia Skokowa, Karl Welte, David C Dale
Journal: Blood (2018)
Abstract MP65: Metabolomics Associated With Augmentation Index and Pulse Wave Velocity: Findings From the Bogalusa Heart Study
Authors: Changwei Li, Jiang He, Shengxu Li, Wei Chen, Lydia Bazzano, Xiao Sun, Luqi Shen, Xiaoying Gu, Tanika Kelly
Journal: Circulation (2018)

Background: Large scale untargeted metabolomics studies are needed to understand the mechanisms of arterial stiffness. Methods: We performed untargeted metabolomics profiling among 1,239 participants of the biracial Bogalusa Heart Study. After quality control, 1,202 metabolites were evaluated for associations with augmentation index (AI) and pulse-wave velocity (PWV) overall and by race, adjusting for age, sex, education, smoking, drinking, body mass index, and physical activity. Weighted correlation network analysis (WGCNA) was applied to build metabolites modules among all participants. Bonferroni correction was used to determine significant metabolites. Significant metabolites should also have P &lt;0.05 and consistent effect directions in both races. Results: We identified 4 and 17 novel metabolites associated with AI and PWV, respectively ( Table ). We also replicated associations of 12 previously reported metabolites with PWV in the overall sample, including 1,5-anhydroglucitol ( P =5.55E-9), glucose ( P =8.19E-14), glutamic acid ( P =1.56E-8), glycine ( P =9.87E-6), serine ( P =0.003), urea ( P =0.03), uridine ( P =0.002), glutamine ( P =0.001), 3-phenylpropionate ( P =0.004), trans-4-hydroxyproline ( P =0.001), pyruvate ( P =0.002), and lysine ( P =0.007). WGCNA identified two modules in significant associations with both AI ( P =3E-4 and 8E-4, respectively) and PWV ( P =2E-6 and 7E-5, respectively). One module was composed of metabolites of glycerolipids recycling pathway. The other module consisted of amino acids involved in glutamate, leucine, isoleucine, valine, methionione, systein, taurine, and alanine metabolisms. WGCNA also identified a network of sphingolipid metabolism for PWV ( P =0.002). Investigation to hub metabolites of these modules identified 3 novel metabolites for AI and 4 novel metabolites for PWV ( Table ). Conclusions: The current study identified important metabolites and metabolites networks associated with AI and PWV.
Adolescent girls’ nutrition and prevention of anaemia: a school based multisectoral collaboration in Indonesia
Authors: Marion Leslie Roche, Louise Bury, Isma Novitasari Yusadiredja, Eriana Kartika Asri, Tutut Sri Purwanti, Sri Kusyuniati, Anjali Bhardwaj, Doddy Izwardy
Journal: BMJ (2018)

<b>Marion Roche and colleagues</b> highlight lessons from a multisectoral project implementing weekly iron supplementation for adolescent girls in West Java, Indonesia, which provides a scalable model for reducing anaemia
STING-mediated inflammation in Kupffer cells contributes to progression of nonalcoholic steatohepatitis
Authors: Yongsheng Yu, Yu Liu, Weishuai An, Jingwen Song, Yuefan Zhang, Xianxian Zhao
Journal: Journal of Clinical Investigation (2018)

Innate immune activation contributes to the transition from nonalcoholic fatty liver to nonalcoholic steatohepatitis (NASH). Stimulator of IFN genes (STING, also referred to Tmem173) is a universal receptor that recognizes released DNA and triggers innate immune activation. In this work, we investigated the role of STING in the progression of NASH in mice. Both methionine- and choline-deficient diet (MCD) and high-fat diet (HFD) were used to induce NASH in mice. Strikingly, STING deficiency attenuated steatosis, fibrosis, and inflammation in livers in both murine models of NASH. Additionally, STING deficiency increased fasting glucose levels in mice independently of insulin, but mitigated HFD-induced insulin resistance and weight gain and reduced levels of cholesterol, triglycerides, and LDL in serum; it also enhanced levels of HDL. The mitochondrial DNA (mtDNA) from hepatocytes of HFD-fed mice induced TNF-α and IL-6 expression in cultured Kupffer cells (KCs), which was attenuated by STING deficiency or pretreatment with BAY11-7082 (an NF-κB inhibitor). Finally, chronic exposure to 5,6-dimethylxanthenone-4-acetic acid (DMXAA, a STING agonist) led to hepatic steatosis and inflammation in WT mice, but not in STING-deficient mice. We proposed that STING functions as an mtDNA sensor in the KCs of liver under lipid overload and induces NF-κB-dependent inflammation in NASH.
Letter to the editor: Is malaria re-emerging in southern Europe? Cryptic Plasmodium falciparum malaria in Malta, October 2018
Authors: Raquel Medialdea-Carrera, Tanya Melillo, Charmaine Gauci, Graziella Rocco, Maria Louise Borg
Journal: Eurosurveillance (2018)

Preview this article: Letter to the editor: Is malaria re-emerging in southern Europe? Cryptic Plasmodium falciparum malaria in Malta, October 2018, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/23/50/eurosurv-23-50-5-1.gif
Viral MHCI inhibition evades tissue-resident memory T cell formation and responses
Authors: Elvin J. Lauron, Liping Yang, Ian B. Harvey, Dorothy K. Sojka, Graham D. Williams, Michael A. Paley, Michael D. Bern, Eugene Park, Francisco Victorino, Adrianus C.M. Boon, Wayne M. Yokoyama
Journal: The Journal of Experimental Medicine (2018)

Tissue-resident memory CD8+ T cells (TRMs) confer rapid protection and immunity against viral infections. Many viruses have evolved mechanisms to inhibit MHCI presentation in order to evade CD8+ T cells, suggesting that these mechanisms may also apply to TRM-mediated protection. However, the effects of viral MHCI inhibition on the function and generation of TRMs is unclear. Herein, we demonstrate that viral MHCI inhibition reduces the abundance of CD4+ and CD8+ TRMs, but its effects on the local microenvironment compensate to promote antigen-specific CD8+ TRM formation. Unexpectedly, local cognate antigen enhances CD8+ TRM development even in the context of viral MHCI inhibition and CD8+ T cell evasion, strongly suggesting a role for in situ cross-presentation in local antigen-driven TRM differentiation. However, local cognate antigen is not required for CD8+ TRM maintenance. We also show that viral MHCI inhibition efficiently evades CD8+ TRM effector functions. These findings indicate that viral evasion of MHCI antigen presentation has consequences on the development and response of antiviral TRMs.
Wnt5a causes ROR1 to complex and activate cortactin to enhance migration of chronic lymphocytic leukemia cells
Authors: Md Kamrul Hasan, Laura Rassenti, George F. Widhopf, Jian Yu, Thomas J. Kipps
Journal: Leukemia (2018)

Chronic lymphocytic leukemia cells (CLL) migrate between the blood and lymphoid tissues in response to chemokines. Such migration requires structured cytoskeletal-actin polymerization, which may involve the protein cortactin. We discovered that treatment of CLL cells with Wnt5a causes Receptor tyosin kinase-like orphan receptor 1 (ROR1) to bind cortactin, which undergoes tyrosine phosphorylation at Y421, recruits ARHGEF1, and activates RhoA, thereby enhancing leukemia-cell migration; such effects could be inhibited by cirmtuzumab, a humanized mAb specific for ROR1. We transfected the CLL-cell-line MEC1 with either full-length ROR1 or various mutant forms of ROR1 to examine the structural features required for binding cortactin. We found that the proline-rich domain (PRD) was necessary for ROR1 to recruit cortactin. We generated MEC1 cells that each expressed a mutant form of ROR1 with a single amino-acid substitution of alanine (A) for proline (P) in potential SH3-binding sites in the ROR1-PRD at positions 784, 808, 826, 841, or 850. In contrast to wild-type ROR1, or other ROR1P=>A mutants, ROR1P(841)A failed to complex with cortactin or ARHGEF1 in response to Wnt5a. Moreover, Wnt5a could not induce MEC1-ROR1P(841)A to phosphorylate cortactin or enhance CLL-cell F-actin polymerization. Taken together, these studies show that cortactin plays an important role in ROR1-dependent Wnt5a-enhanced CLL-cell migration.
Abstract 20786: Gender Difference in the Prediction of Mortality Using High-Sensitivity Cardiac Troponin I in Stable Patients With and Without Coronary Artery Disease
Authors: Jan S Wolter, Steffen Kriechbaum, Tim Streib, Matthis Weinert, Oliver Dörr, Claudia Walther, Christian Troidl, Helge Möllmann, Holger Nef, Andreas Rolf, Alexander Berkowitsch, Till Keller, Christian W Hamm, Christoph Liebetrau
Journal: Circulation (2017)

Introduction: The decision about whether to carry out coronary angiography (CAG) in patients with stable coronary artery disease (CAD) is challenging. The use of specific markers of cardiac disease is pivotal to decision making. High-sensitivity cardiac troponin I (hs-cTnI) has emerged as in important biomarker in predicting prognosis. Even in the majority of the “healthy” population it is possible to detect high-sensitivity cardiac troponin I (hs-cTnI). Hypothesis: The aim of this study was to characterize the influence of gender differences and prevalent CAD on the prognostic value of hs-cTnI. Methods: A total of 4252 stable patients undergoing CAG were included in the study. The primary endpoint was defined as all-cause mortality, the secondary combined endpoint as all-cause mortality and non-fatal MI. Serum hs-cTnI was measured in all patients before CAG. In a further analysis patients with severe valve diseases and/or left ventricular ejection fraction below 30% were excluded to eliminate confounders...
Identification and Isolation of Tumor-Specific Cytotoxic T Lymphocytes in Acute Myeloid Leukemia Patients through the Identification of T-Cells Capable to Establish Stable Interactions with Leukemic Cells
Authors: Estefania Garcia-Guerrero, Luis I. Sanchez-Abarca, Esther Domingo, Teresa Ramos, Jose Antonio Bejarano-García, Jose A Gonzalez-Campos, Teresa Caballero-Velázquez, José A. Pérez-Simón
Journal: Blood (2018)
Standardization of 18F-FDG PET/CT According to Deauville Criteria for MRD Evaluation in Newly Diagnosed Transplant Eligible Multiple Myeloma Patients: Joined Analysis of Two Prospective Randomized Phase III Trials
Authors: Elena Zamagni, Cristina Nanni, Luca Dozza, Thomas Carlier, Paola Tacchetti, Annibale Versari, Stephane Chauvie, Andrea Gallamini, Michel Attal, Barbara Gamberi, Denis Caillot, Francesca Patriarca, Margaret Macro, Mario Boccadoro, Laurent Garderet, Stefano Fanti, Aurore Perrot, Francesca Gay, Pieter Sonneveld, Lionel Karlin, Michele Cavo, Caroline Bodet-Milin, Philippe Moreau, Francoise Kraeber-Bodere
Journal: Blood (2018)
Transactivation of RAGE mediates angiotensin-induced inflammation and atherogenesis
Authors: Raelene J. Pickering, Christos Tikellis, Carlos J. Rosado, Despina Tsorotes, Alexandra Dimitropoulos, Monique Smith, Olivier Huet, Ruth M. Seeber, Rekhati Abhayawardana, Elizabeth K.M. Johnstone, Jonathan Golledge, Yutang Wang, Karin A. Jandeleit-Dahm, Mark E. Cooper, Kevin D.G. Pfleger, Merlin C. Thomas
Journal: Journal of Clinical Investigation (2018)

Activation of the type 1 angiotensin II receptor (AT1) triggers proinflammatory signaling through pathways independent of classical Gq signaling that regulate vascular homeostasis. Here, we report that the AT1 receptor preformed a heteromeric complex with the receptor for advanced glycation endproducts (RAGE). Activation of the AT1 receptor by angiotensin II (Ang II) triggered transactivation of the cytosolic tail of RAGE and NF-κB-driven proinflammatory gene expression independently of the liberation of RAGE ligands or the ligand-binding ectodomain of RAGE. The importance of this transactivation pathway was demonstrated by our finding that adverse proinflammatory signaling events induced by AT1 receptor activation were attenuated when RAGE was deleted or transactivation of its cytosolic tail was inhibited. At the same time, classical homeostatic Gq signaling pathways were unaffected by RAGE deletion or inhibition. These data position RAGE transactivation by the AT1 receptor as a target for vasculoprotective interventions. As proof of concept, we showed that treatment with the mutant RAGE peptide S391A-RAGE362-404 was able to inhibit transactivation of RAGE and attenuate Ang II-dependent inflammation and atherogenesis. Furthermore, treatment with WT RAGE362-404 restored Ang II-dependent atherogenesis in Ager/Apoe-KO mice, without restoring ligand-mediated signaling via RAGE, suggesting that the major effector of RAGE activation was its transactivation.
Percutaneous Coronary Intervention in Patients Without Acute Myocardial Infarction in China
Authors: Yuan Lu, Haibo Zhang, Yongfei Wang, Tianna Zhou, John Welsh, Jiamin Liu, Wenchi Guan, Jing Li, Xi Li, Xin Zheng, John A. Spertus, Frederick A. Masoudi, Harlan M. Krumholz, Lixin Jiang
Journal: JAMA Network Open (2018)

Despite a rapid increase in percutaneous coronary intervention (PCI) procedures in China, little is known about patient-reported health status before and after PCI in patients without acute myocardial infarction (AMI).To describe self-perceived angina-specific health status prior to PCI and 1 year after the procedure in patients without AMI in China.The China Patient-Centered Evaluative Assessment of Cardiac Events (PEACE) Prospective Study of PCI was a population-based, multicenter cohort study of a consecutive sample of 1611 patients without AMI undergoing elective PCI. Participants were enrolled from 40 hospitals in 18 provinces in China from December 2012 to August 2014. Participants were eligible if they underwent PCI for stable and unstable angina and did not have AMI. Participants were excluded if they died in hospital, withdrew from follow-up, or had missing data on self-reported health status at baseline or at 1 year after PCI. The date of the analysis was September 15, 2018.Percutaneous coronary intervention for ischemic heart disease.Angina frequency and angina-related quality of life were assessed with the Seattle Angina Questionnaire (SAQ) immediately prior to PCI and 1 year after the procedure. Either (1) an increase in the SAQ Angina Frequency score of 10 or more points or (2) an increase in the SAQ Quality-of-Life score of 10 or more points was considered to represent clinically significant improvement.Of 1611 patients, 520 (32.3%) were women; mean (SD) age was 61.3 (9.8) years. Among these patients, 443 (27.5%) had stable coronary artery disease and 1168 (72.5%) had unstable angina. One hundred fourteen of 443 patients undergoing PCI for stable coronary artery disease (25.7%) and 175 of 1168 undergoing PCI for unstable angina (15.0%) had no reported angina symptoms at the time of the procedure (SAQ Angina Frequency score = 100). Moreover, 18% of all patients (290) had minimal angina symptoms (SAQ Angina Frequency score >90) and, thus, no potential for substantial clinical improvement. Patients with smaller clinical improvements in angina symptom burden at 1 year following PCI had significantly higher baseline SAQ scores for all scales than patients with greater clinical improvement, but generally similar sociodemographic and procedural characteristics.In this study, 25.7% of patients undergoing PCI for stable coronary artery disease had no reported angina symptoms at the time of the procedure. Patients with smaller clinical improvements in angina symptom burden had higher baseline SAQ scores, which highlights the importance of ascertaining impairment from angina among patients without AMI prior to performing PCI.
Abstract 17754: Human iPSC-Derived Myocyte Mmodel of SCN5A-D1275N-Related Cardiac Sodium Channelopathy Reveals Diminished Sodium Currents Resulting From Enhanced Protein Degradation
Authors: Mamoru Hayano, Takeru Makiyama, Tsukasa Kamakura, Hiroshi Watanabe, Kenichi Sasaki, Shunsuke Funakoshi, Yimin Wuriyanghai, Suguru Nishiuchi, Takeshi Harita, Yuta Yamamoto, Hirohiko Kohjitani, Sayako Hirose, Fumika Yokoi, Jiarong Chen, Osamu Baba, Takahiro Horie, Kazuhisa Chonabayashi, Seiko Ohno, Futoshi Toyoda, Yoshinori Yoshida, Koh Ono, Minoru Horie, Takeshi Kimura
Journal: Circulation (2017)

Introduction: The SCN5A gene encodes the α subunit of the cardiac sodium (Na+) channel, NaV1.5. The missense mutation, D1275N, has been associated with a range of unusual phenotypes associated with...
Facilitating Resolution of Life-Threatening Acute Graft-Versus-Host Disease By Supplementation of Human Chorionic Gonadotropin and Epidermal Growth Factor (Pregnyl): A Phase I Study
Authors: Shernan G. Holtan, Andrea Hoeschen, Qing Cao, Mukta Arora, Veronika Bachanova, Claudio G Brunstein, Sarah Cooley, Jeffrey S. Miller, Arne Slungaard, Celalettin Ustun, Armin Rashidi, Gregory M Vercellotti, Erica D. Warlick, Todd E. DeFor, John E. Wagner, Bruce R. Blazar, Pamala A. Jacobson, Angela Panoskaltsis-Mortari, Margaret L. MacMillan, Daniel J. Weisdorf
Journal: Blood (2018)
Sustainability of Blood Pressure Reduction in Black Barbershops
Authors: Ronald G. Victor, Ciantel A. Blyler, Ning Li, Kathleen Lynch, Norma B. Moy, Mohamad Rashid, L. Cindy Chang, Joel Handler, Jeffrey Brettler, Florian Rader, Robert M. Elashoff
Journal: Circulation (2018)

Background: We developed a new model of hypertension care for non-Hispanic black men that links health promotion by barbers to medication management by American Society of Hypertension–certified pharmacists and demonstrated efficacy in a 6-month cluster-randomized trial. The marked reduction in systolic blood pressure (BP) seen at 6 months warranted continuing the trial through 12 months to test sustainability, a necessary precondition for implementation research. Methods: We enrolled a cohort of 319 black male patrons with systolic BP ≥140 mm Hg at baseline. Fifty-two Los Angeles County barbershops were assigned to either a pharmacist-led intervention or an active control group. In the intervention group, barbers promoted follow-up with pharmacists who prescribed BP medication under a collaborative practice agreement with patrons’ primary care providers. In the control group, barbers promoted follow-up with primary care providers and lifestyle modification. After BP assessment at 6 months, the intervention continued with fewer in-person pharmacist visits to test whether the intervention effect could be sustained safely for 1 year while reducing pharmacist travel time. Final BP and safety outcomes were assessed in both groups at 12 months. Results: At baseline, mean systolic BP was 152.4 mm Hg in the intervention group and 154.6 mm Hg in the control group. At 12 months, mean systolic BP fell by 28.6 mm Hg (to 123.8 mm Hg) in the intervention group and by 7.2 mm Hg (to 147.4 mm Hg) in the control group. The mean reduction was 20.8 mm Hg greater in the intervention (95% CI, 13.9–27.7; P &lt;0.0001). A BP &lt;130/80 mm Hg was achieved by 68.0% of the intervention group versus 11.0% of the control group ( P &lt;0.02). These new 12-month efficacy data are statistically indistinguishable from our previously reported 6-month data. No treatment-related serious adverse events occurred in either group over 12 months. Cohort retention at 12 months was 90% in both groups. Conclusions: Among black male barbershop patrons with uncontrolled hypertension, health promotion by barbers resulted in large and sustained BP reduction over 12 months when coupled with medication management by American Society of Hypertension–certified pharmacists. Broad-scale implementation research is both justified and warranted. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT 02321618.
Facial Feminization Surgery: Privacy, Personal Identity, Compensatory Justice, and Resource Allocation
Authors: Lauren Notini, Lynn Gillam, Ken C. Pang
Journal: The American Journal of Bioethics (2018)

Dubov and Fraenkel (2018) argue that facial feminization surgery (FFS) should be properly regarded as “medically necessary” and therefore should be covered by insurance. They note that FFS not only...
40 Is the New 50: Reducing the Need for Platelet Transfusions Prior to Lumbar Puncture in Patients with Hematologic Malignancies
Authors: Kristen M Corrao, Laura C. Michaelis, Lisa Baumann Kreuziger, Karen-Sue B. Carlson, Sameem Abedin, Elizabeth Malosh, David Atkinson, Wenjing Shan, Stephen Quinet, Adrian P Umpierrez De Reguero, DeLisle Julie, Angela Treml, Lyndsey Runaas, Ehab L. Atallah
Journal: Blood (2018)
MACRA’s Patient Relationship Codes — Measuring Accountability for Costs
Authors: Samuel U. Takvorian, Justin E. Bekelman, Matthew J. Press
Journal: New England Journal of Medicine (2018)

Billing-code modifiers allow clinicians to report their relationship to the patient at a given point in time and for a particular service rendered. Ultimately, they will be used to assess clinician performance, particularly with respect to resource utilization and cost.
Relation between IDH1 status, histologic grade, immune-cell infiltration and expression of immune-related genes in patients with gliomas
Authors: S. Cabezas-Camarero, R. Pérez-Alfayate, I. Casado Fariñas, M. Sáiz-Pardo Sanz, I. Subhi-Issa, P. Pérez-Segura, V. García-Barberán
Journal: Annals of Oncology (2018)

Background: Very few data exist regarding the immune profile of gliomas. Our aim was to study different immunological parameters according to IDH1 mutational status and histologic grade. Methods: Patients with grade II to IV gliomas were prospectively enrolled. Immunohistochemistry (IHC) was used to quantify CD4+ and CD8+ T cells and to study IDH1 and PDL1 (> 5%) expression on tumor cells. These parameters were correlated to mRNA expression of 20 immune-related genes (CSF1R, CTLA4, CXCL9, CXCL10, CXCL13, FOXP3, GZMA, HLADRA, IDO1, INFG, PD1, PDL1, PDL2, PRF1, STAT1, STAT3, TIGIT, TIM3, VISTA, TLR7) according to IDH1 status and histologic grade. Results: Between February 2017 and July 2018, 20 patients (pts) were enrolled, 14 glioblastomas (GB: 9 IDHWT, 5 IDH1MUT) and 6 lower-grade gliomas (LGG: 2 IDHWT, 4 IDHMUT). Among 18 pts: PDL1 IHC was positive (PDL1IHC+) in 10 GB (3 IDH1MUT) and 1 LGG (IDH1MUT); CD4+ T cell infiltration (intratumoral (IT)/perivascular(PV)) in 5 GB (2 IDH1MUT); CD8+ T cell infiltration in 12 GB (8 IT+PV, 3 IT, 1 PV) and 5 LGG (1 IT, 4 IT+PV). PDL1IHC+ more frequent in GB + LGGIDH1wt vs LGGIDH1mut (P = 0.06). PDL1IHC+ tumors shoed lower expression of STAT1 (P = 0.042), TIM3 (P = 0.02) and TLR7 (P = 0.06). Tumors with > 20 CD8+ T cells/HPF showed higher expression of PD1 (P = 0.03), PRF1 (P = 0.03) and STAT1 (P = 0.03). Conclusions: Histologic grade and IDH1 status identify glioma groups with different immunophenotypes. This results should be confirmed in a larger sample. Legal entity responsible for the study: Santiago Cabezas. Funding: GEINO (Grupo Español de Investigación en Neuro-Oncología). Disclosure: All authors have declared no conflicts of interest.