tbuckley/cabot-search huggingface dataset:
Liver stiffness measurement by 2D SWE from General Electric is similar with Transient Elastography in clinical significant portal hypertension diagnosis
Authors: R. Corina, B. Procopet, M. Platon, A. Maniu, F. Petra, C. Grigoras, A. Bugariu, M. Tantau, R. Badea, H. Stefanescu
Journal: Journal of Hepatology (2018)
Glycosaminoglycan-based hybrid hydrogel encapsulated with polyelectrolyte complex nanoparticles for endogenous stem cell regulation in central nervous system regeneration
Authors: Wei-Hong Jian, Huan-Chih Wang, Chen-Hsiang Kuan, Ming-Hong Chen, Hsi-Chin Wu, Jui-Sheng Sun, Tzu-Wei Wang
Journal: Biomaterials (2018)
Prediction of Normal Organ Absorbed Doses for [177Lu]Lu-PSMA-617 Using [44Sc]Sc-PSMA-617 Pharmacokinetics in Patients With Metastatic Castration Resistant Prostate Carcinoma
Authors: Ambreen Khawar, Elisabeth Eppard, Jean Phlippe Sinnes, Frank Roesch, Hojjat Ahmadzadehfar, Stefan Kürpig, Michael Meisenheimer, Florian C. Gaertner, Markus Essler, Ralph A. Bundschuh
Journal: Clinical Nuclear Medicine (2018)

Aim In vivo pharmacokinetic analysis of [ 44 Sc]Sc-PSMA-617 was used to determine the normal organ-absorbed doses that may result from therapeutic activity of [ 177 Lu]Lu-PSMA-617 and to predict the maximum permissible activity of [ 177 Lu]Lu-PSMA-617 for patients with metastatic castration-resistant prostate carcinoma. Methods Pharmacokinetics of [ 44 Sc]Sc-PSMA-617 was evaluated in 5 patients with metastatic castration-resistant prostate carcinoma using dynamic PET/CT, followed by 3 static PET/CT acquisitions and blood sample collection over 19.5 hours, as well as urine sample collection at 2 time points. Total activity measured in source organs by PET imaging, as well as counts per milliliter measured in blood and urine samples, was decay corrected back to the time of injection using the half-life of 44 Sc. Afterward, forward decay correction using the half-life of 177 Lu was performed, extrapolating the pharmacokinetics of [ 44 Sc]Sc-PSMA-617 to that of [ 177 Lu]Lu-PSMA-617. Source organs residence times and organ-absorbed doses for [ 177 Lu]Lu-PSMA-617 were calculated using OLINDA/EXM software. Bone marrow self-dose was determined with indirect blood-based method, and urinary bladder contents residence time was estimated by trapezoidal approximation. The maximum permissible activity of [ 177 Lu]Lu-PSMA-617 was calculated for each patient considering external beam radiotherapy toxicity limits for radiation absorbed doses to kidneys, bone marrow, salivary glands, and whole body. Results The predicted mean organ-absorbed doses were highest in the kidneys (0.44 mSv/MBq), followed by the salivary glands (0.23 mSv/MBq). The maximum permissible activity was highly variable among patients; limited by whole body–absorbed dose (1 patient), marrow-absorbed dose (1 patient), and kidney-absorbed dose (3 patients). Conclusions [ 44 Sc]Sc-PSMA-617 PET/CT imaging is feasible and allows theoretical extrapolation of the pharmacokinetics of [ 44 Sc]Sc-PSMA-617 to that of [ 177 Lu]Lu-PSMA-617, with the intent of predicting normal organ-absorbed doses and maximum permissible activity in patients scheduled for therapy with [ 177 Lu]Lu-PSMA-617.
R-spondin3 Is Associated with Basal-Progenitor Behavior in Normal and Tumor Mammary Cells
Authors: Johanna M. Tocci, Carla M. Felcher, Martín E. García Solá, María Victoria Goddio, María Noel Zimberlin, Natalia Rubinstein, Anabella Srebrow, Omar A. Coso, Martín C. Abba, Roberto P. Meiss, Edith C. Kordon
Journal: Cancer Research (2018)

Abstract R-spondin3 (RSPO3) is a member of a family of secreted proteins that enhance Wnt signaling pathways in diverse processes, including cancer. However, the role of RSPO3 in mammary gland and breast cancer development remains unclear. In this study, we show that RSPO3 is expressed in the basal stem cell–enriched compartment of normal mouse mammary glands but is absent from committed mature luminal cells in which exogenous RSPO3 impairs lactogenic differentiation. RSPO3 knockdown in basal-like mouse mammary tumor cells reduced canonical Wnt signaling, epithelial-to-mesenchymal transition-like features, migration capacity, and tumor formation in vivo. Conversely, RSPO3 overexpression, which was associated with some LGR and RUNX factors, highly correlated with the basal-like subtype among patients with breast cancer. Thus, we identified RSPO3 as a novel key modulator of breast cancer development and a potential target for treatment of basal-like breast cancers. Significance: These findings identify RSPO3 as a potential therapetuic target in basal-like breast cancers. Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/16/4497/F1.large.jpg. Cancer Res; 78(16); 4497–511. ©2018 AACR.
2018 ACC/HRS/NASCI/SCAI/SCCT Expert Consensus Document on Optimal Use of Ionizing Radiation in Cardiovascular Imaging—Best Practices for Safety and Effectiveness, Part 1: Radiation Physics and Radiation Biology
Authors: John W. Hirshfeld, Victor A. Ferrari, Frank M. Bengel, Lisa Bergersen, Charles E. Chambers, Andrew J. Einstein, Mark J. Eisenberg, Mark A. Fogel, Thomas C. Gerber, David E. Haines, Warren K. Laskey, Marian C. Limacher, Kenneth J. Nichols, Daniel A. Pryma, Gilbert L. Raff, Geoffrey D. Rubin, Donnette Smith, Arthur E. Stillman, Suma A. Thomas, Thomas T. Tsai, Louis K. Wagner, L. Samuel Wann
Journal: Journal of the American College of Cardiology (2018)
Abstract 41: Cardiomyocyte-specific Conditional Deletion of GSK-3β Leads to Cardiac Dysfunction in a High Fat Diet Induced Obesity Model
Authors: Manisha Gupte, Samvruta Tumuluru, Anand P Singh, Prachi Umbarkar, Qinkun Zhang, Firdos Ahmad, Shan Parikh, Thomas Force, Hind Lal
Journal: Circulation Research (2017)

Introduction: Previous studies from our group have demonstrated that cardiac myocyte glycogen synthase kinase-3’s (GSK-3) are required to maintain normal cardiac physiology. Adult mice lacking both isoforms of GSK-3 (α and β) in cardiac myocytes exhibit excessive dilatative remodeling and ventricular dysfunction ultimately leading to death. While high fat diet (HFD) induced obesity is associated with increased risk of cardiovascular disease, the specific role of cardiac GSK-3α or GSK-3β in obesity-associated cardiac dysfunction is unknown. Objective: The primary goal of the present study was to investigate the role of cardiomyocyte GSK-3β in cardiac homeostasis in HFD-induced chronic obesity model. Method: Cardiomyocyte specific-GSK-3β knock out (CM-GSK-3βKO) and wild type (WT) mice were fed either a chow (11.5% calories from fat) or high-fat (60% calories from fat) for 24 weeks. Cardiac function was accessed by non-invasive transthoracic echocardiography. Results: HFD significantly increased body weight, lean and fat mass in the WT and CM-GSK-3βKO compared to chow. However, there was no difference in body weights, lean and fat mass between the two genotypes fed either a chow or HFD. Furthermore, ventricular chamber dimensions and cardiac function were comparable between the WT and CM-GSK-3βKO mice fed a chow diet. In contrast, high fat fed CM-GSK-3βKO hearts exhibit significant cardiac hypertrophy (heart weight/tibia length ratio) and ventricular dysfunction (reduced ejection fraction (EF) and fractional shortening (FS)) compared to the WT. Interestingly cardiomyocytes from HF fed CM-GSK-3βKO exhibit structural abnormalities and increased expression of pro-apoptotic protein Bax and reduced expression of Bcl-2, an anti-apoptotic protein. Conclusion: In summary, these data suggests that cardiac GSK-3β is important in the setting of HFD-induced chronic obesity to maintain cardiac function. In the absence of GSK-3β, cardiomyocytes undergo morphometric abnormalities, excessive fat infiltration and apoptosis leading to cardiac dysfunction.
Antibody Responses to Citrullinated and Noncitrullinated Antigens in the Sputum of Subjects With Rheumatoid Arthritis and Subjects at Risk for Development of Rheumatoid Arthritis
Authors: M. Kristen Demoruelle, Emily Bowers, Lauren J. Lahey, Jeremy Sokolove, Monica Purmalek, Nickie L. Seto, Michael H. Weisman, Jill M. Norris, Mariana J. Kaplan, V. Michael Holers, William H. Robinson, Kevin D. Deane
Journal: Arthritis & Rheumatology (2017)

Objective The location and mechanisms involved in the initial generation of autoantibodies to citrullinated and noncitrullinated proteins/peptides during the natural history of rheumatoid arthritis ( RA ) development is incompletely understood. This study sought to explore individual antibody responses to citrullinated and noncitrullinated proteins/peptides in the sputum and associations with neutrophil extracellular traps ( NET s) in subjects at risk for the future development of RA . Methods Serum and sputum samples were obtained from 41 RA ‐free subjects who were considered at risk for the development of RA based on familial or serologic risk factors, from 20 subjects classified as having RA , and from 22 healthy control subjects. Samples were evaluated using a bead‐based array for IgG reactivity to 29 citrullinated proteins/peptides and 21 noncitrullinated proteins/peptides. Cutoff levels for antibody positivity were established in a separate control group. NET levels in the sputum were measured using sandwich enzyme‐linked immunosorbent assays that quantitate DNA –myeloperoxidase and DNA –neutrophil elastase complexes. Results In at‐risk subjects, antibody responses to the citrullinated forms of fibrinogen, apolipoprotein E, and fibronectin were highly prevalent. The most citrulline‐specific antibodies in the sputum of at‐risk subjects were those to fibrinogen, vimentin, and peptides of fibrinogen A and apolipoprotein A1. Patterns of sputum autoantibody positivity differed between at‐risk subjects and subjects with RA . In at‐risk subjects, increasing sputum NET levels significantly correlated with several citrullinated and some noncitrullinated antibody reactivities. Conclusion These findings suggest that sputum antibody reactivity to particular citrullinated and noncitrullinated proteins/peptides is specific for RA and for subjects at risk of RA , and the association of these proteins/peptides with NET s may be a key feature of early RA –related autoimmunity in the lung. These results further support the hypothesis that the lung plays a role in early RA –related autoimmunity.
Predictive and Prognostic Significance of Immunohistochemical Markers and Blood Absolute Lymphocyte Count in Diffuse Large B-Cell Lymphoma in Rituximab Era: A Polish Lymphoma Research Group (PLRG) Multicenter Retrospective Analysis
Authors: Anna Czyz, Monika Joks, Joanna E Drozd-Sokolowska, Wanda Knopinska-Posluszny, Magdalena Zawartko, Ewa Mizera-Nyczak, Dominik Dytfeld, Barbara Zdziarska, Wiktor-Wieslaw Jedrzejczak, Mieczyslaw Komarnicki
Journal: Blood (2014)
Sustained Reduction in Severe Hypoglycemia in Adults With Type 1 Diabetes Complicated by Impaired Awareness of Hypoglycemia: Two-Year Follow-up in the HypoCOMPaSS Randomized Clinical Trial
Authors: Stuart A. Little, Jane Speight, Lalantha Leelarathna, Emma Walkinshaw, Horng Kai Tan, Anita Bowes, Alexandra Lubina-Solomon, Thomas J. Chadwick, Deborah D. Stocken, Catherine Brennand, Sally M. Marshall, Ruth Wood, David Kerr, Daniel Flanagan, Simon R. Heller, Mark L. Evans, James A.M. Shaw
Journal: Diabetes Care (2018)

OBJECTIVE Severe hypoglycemia is a feared complication of type 1 diabetes; yet, few trials have targeted prevention using optimized self-management (educational, therapeutic, and technological support). We aimed to investigate whether improved awareness and reduced severe hypoglycemia, achieved during an intensive randomized clinical trial (RCT), were sustained after return to routine care. RESEARCH DESIGN AND METHODS Ninety-six adults with type 1 diabetes (29 ± 12 years’ duration) and impaired awareness of hypoglycemia at five U.K. tertiary referral diabetes centers were recruited into a 24-week 2 × 2 factorial RCT (HypoCOMPaSS). Participants were randomized to pump (continuous subcutaneous insulin infusion [CSII]) or multiple daily injections (MDIs) and real-time continuous glucose monitoring (RT-CGM) or self-monitoring of blood glucose (SMBG), with equal education/attention to all groups. At 24 weeks, participants returned to routine care with follow-up until 24 months, including free choice of MDI/CSII; RT-CGM vs. SMBG comparison continued to 24 months. Primary outcome was mean difference (baseline to 24 months [between groups]) in hypoglycemia awareness. RESULTS Improvement in hypoglycemia awareness was sustained (Gold score at baseline 5.1 ± 1.1 vs. 24 months 3.7 ± 1.9; P &amp;lt; 0.0001). Severe hypoglycemia rate was reduced from 8.9 ± 12.8 episodes/person-year over the 12 months prestudy to 0.4 ± 0.8 over 24 months (P &amp;lt; 0.0001). HbA1c improved (baseline 8.2 ± 3.2% [66 ± 12 mmol/mol] vs. 24 months 7.7 ± 3.1% [61 ± 10 mmol/mol]; P = 0.003). Improvement in treatment satisfaction and reduced fear of hypoglycemia were sustained. There were no significant differences between interventions at 24 months. CONCLUSIONS Optimized insulin replacement and glucose monitoring underpinned by hypoglycemia-focused structured education should be provided to all with type 1 diabetes complicated by impaired awareness of hypoglycemia.
Changes of bile acids profile in different etiologies of liver cirrhosis and its association with neutrophil response
Authors: I. Komarova, A. Horvath, E. Krones, B. Leber, B. Schmerboeck, F. Durchschein, G. Zollner, R.E. Stauber, W. Spindelböck, P. Douschan, P. Stiegler, D. Kniepeiss, T. Stojakovic, Günter Fauler, V. Stadlbauer
Journal: Journal of Hepatology (2018)
Long-Term Plasticity of Neurotransmitter Release: Emerging Mechanisms and Contributions to Brain Function and Disease
Authors: Hannah R. Monday, Thomas J. Younts, Pablo E. Castillo
Journal: Annual Review of Neuroscience (2018)

Long-lasting changes of brain function in response to experience rely on diverse forms of activity-dependent synaptic plasticity. Chief among them are long-term potentiation and long-term depression of neurotransmitter release, which are widely expressed by excitatory and inhibitory synapses throughout the central nervous system and can dynamically regulate information flow in neural circuits. This review article explores recent advances in presynaptic long-term plasticity mechanisms and contributions to circuit function. Growing evidence indicates that presynaptic plasticity may involve structural changes, presynaptic protein synthesis, and transsynaptic signaling. Presynaptic long-term plasticity can alter the short-term dynamics of neurotransmitter release, thereby contributing to circuit computations such as novelty detection, modifications of the excitatory/inhibitory balance, and sensory adaptation. In addition, presynaptic long-term plasticity underlies forms of learning and its dysregulation participates in several neuropsychiatric conditions, including schizophrenia, autism, intellectual disabilities, neurodegenerative diseases, and drug abuse.
Appraisal of prognostic interaction between sidedness and histology in colon cancer: A population-based study.
Authors: Lu-Ping Yang, Zi-Xian Wang, Ying-Nan Wang, Feng Wang, Rui-hua Xu
Journal: Journal of Clinical Oncology (2018)

649 Background: It is reported that sidedness (right vs. left) and histology (mucinous vs. non-mucinous) of CC is predictive of survival. We investigated whether the prognostic values of sidedness and histology were affected by each other. Methods: We identified 81342 patients with stage II–IV CC between 2004 and 2012 from the Surveillance, Epidemiology, and End Results database. Inverse probability propensity score weighting was used to balance the clinical features (i.e., age, sex, race, marital status, year of diagnosis, registry, tumor grade, and T and N stage) between the non-mucinous right-sided, non-mucinous left-sided, mucinous right-sided, and mucinous left-sided subgroups with stratification for tumor stage. Afterwards, overall survival (OS) was compared between these subgroups using univariable Cox proportional hazards models. Results: In stage III/IV CC, the prognosis for non-mucinous left-sided tumors was significantly better than that for non-mucinous right-sided tumors and that for mucinous left-sided tumors, whereas the survival was similar between left-sided and right-sided tumors with the mucinous subtype and between mucinous and non-mucinous tumors in the right-sided colon (Table; test for interaction between sidedness and histology, P &lt; 0.001 in both stages). In stage II CC, the weighted 5-year OS rates were comparable among the four sidedness-histology subgroups (range, 70.3%–72.6%; P= 0.159 and P interaction = 0.466). Conclusions: In stage III/IV CC, the prognostic impact of sidedness differed according to histology, and vice versa. By contrast, neither should be considered in risk stratification for stage II CC. [Table: see text]
Targeting the Leukemia Antigen PR1 with Immunotherapy for the Treatment of Multiple Myeloma
Authors: Gheath Alatrash, Alexander A. Perakis, Celine Kerros, Haley L. Peters, Pariya Sukhumalchandra, Mao Zhang, Haroon Jakher, Madhushree Zope, Rebecca Patenia, Anna Sergeeva, Shuhua Yi, Ken H. Young, Anne V. Philips, Amanda M. Cernosek, Haven R. Garber, Na Qiao, Jinsheng Weng, Lisa S. St John, Sijie Lu, Karen Clise-Dwyer, Elizabeth A. Mittendorf, Qing Ma, Jeffrey J. Molldrem
Journal: Clinical Cancer Research (2018)

Abstract Purpose: PR1 is a human leukocyte antigen (HLA)-A2 nonameric peptide derived from neutrophil elastase (NE) and proteinase 3 (P3). We have previously shown that PR1 is cross-presented by solid tumors, leukemia, and antigen-presenting cells, including B cells. We have also shown that cross-presentation of PR1 by solid tumors renders them susceptible to killing by PR1-targeting immunotherapies. As multiple myeloma is derived from B cells, we investigated whether multiple myeloma is also capable of PR1 cross-presentation and subsequently capable of being targeted by using PR1 immunotherapies. Experimental Design: We tested whether multiple myeloma is capable of cross-presenting PR1 and subsequently becomes susceptible to PR1-targeting immunotherapies, using multiple myeloma cell lines, a xenograft mouse model, and primary multiple myeloma patient samples. Results: Here we show that multiple myeloma cells lack endogenous NE and P3, are able to take up exogenous NE and P3, and cross-present PR1 on HLA-A2. Cross-presentation by multiple myeloma utilizes the conventional antigen processing machinery, including the proteasome and Golgi, and is not affected by immunomodulating drugs (IMiD). Following PR1 cross-presentation, we are able to target multiple myeloma with PR1-CTL and anti-PR1/HLA-A2 antibody both in vitro and in vivo. Conclusions: Collectively, our data demonstrate that PR1 is a novel tumor-associated antigen target in multiple myeloma and that multiple myeloma is susceptible to immunotherapies that target cross-presented antigens. Clin Cancer Res; 24(14); 3386–96. ©2018 AACR.
TCTAP C-207 Atrial Septum Fenestration for Patient with Idiopathic Pulmonary Artery Hypertension
Authors: Tagir Aminov, Irina E. Nikolaeva, Vladimir V. Plechev, Igor V. Buzaev, Bogdan Aleksandrovich Oleynik, Eustaquio M. Onorato, Ilgiz Zagitov, Gulchachak Khalikova
Journal: Journal of the American College of Cardiology (2018)
Sulfatase 2 antagonizes starvation-induced autophagy in hepatocellular carcinoma
Authors: Y. Fang, P. Romecin, S. Wang, E.J. Tolosa, L. Flores, C.D. Moser, S. Han, C. Hu, D. Yang, G. Chen, R. Chaiteerakij, Y. Chen, A. Miamen, P. Kumar, Y. Ha, M.E. Fernandez-Zapico, L. Roberts
Journal: Journal of Hepatology (2018)
Internal migration and transmission dynamics of tuberculosis in Shanghai, China: an epidemiological, spatial, genomic analysis
Authors: Chongguang Yang, Liping Lu, Joshua L Warren, Jie Wu, Qi Jiang, Tianyu Zuo, Mingyu Gan, Mei Liu, Qingyun Liu, Kathryn DeRiemer, Jianjun Hong, Xin Shen, Caroline Colijn, Xiaoqin Guo, Qian Gao, Ted Cohen
Journal: The Lancet Infectious Diseases (2018)
Peribiliary glands and biliary tree stem cells are involved in the pathogenesis of cholangiocarcinoma arising in patients affected by primary sclerosing cholangitis
Authors: D. Overi, V. Cardinale, T. Folseraas, G. Carpino, K. Grzyb, D. Costantini, P.B. Berloco, D. Alvaro, E. Gaudio
Journal: Journal of Hepatology (2018)
CD32 is expressed on cells with transcriptionally active HIV but does not enrich for HIV DNA in resting T cells
Authors: Mohamed Abdel-Mohsen, Leticia Kuri-Cervantes, Judith Grau-Exposito, Adam M. Spivak, Racheal A. Nell, Costin Tomescu, Surya Kumari Vadrevu, Leila B. Giron, Carla Serra-Peinado, Meritxell Genescà, Josep Castellví, Guoxin Wu, Perla M. Del Rio Estrada, Mauricio González-Navarro, Kenneth Lynn, Colin T. King, Sai Vemula, Kara Cox, Yanmin Wan, Qingsheng Li, Karam Mounzer, Jay Kostman, Ian Frank, Mirko Paiardini, Daria Hazuda, Gustavo Reyes-Terán, Douglas Richman, Bonnie Howell, Pablo Tebas, Javier Martinez-Picado, Vicente Planelles, Maria J. Buzon, Michael R. Betts, Luis J. Montaner
Journal: Science Translational Medicine (2018)

The persistence of HIV reservoirs, including latently infected, resting CD4+ T cells, is the major obstacle to cure HIV infection. CD32a expression was recently reported to mark CD4+ T cells harboring a replication-competent HIV reservoir during antiretroviral therapy (ART) suppression. We aimed to determine whether CD32 expression marks HIV latently or transcriptionally active infected CD4+ T cells. Using peripheral blood and lymphoid tissue of ART-treated HIV+ or SIV+ subjects, we found that most of the circulating memory CD32+ CD4+ T cells expressed markers of activation, including CD69, HLA-DR, CD25, CD38, and Ki67, and bore a TH2 phenotype as defined by CXCR3, CCR4, and CCR6. CD32 expression did not selectively enrich for HIV- or SIV-infected CD4+ T cells in peripheral blood or lymphoid tissue; isolated CD32+ resting CD4+ T cells accounted for less than 3% of the total HIV DNA in CD4+ T cells. Cell-associated HIV DNA and RNA loads in CD4+ T cells positively correlated with the frequency of CD32+ CD69+ CD4+ T cells but not with CD32 expression on resting CD4+ T cells. Using RNA fluorescence in situ hybridization, CD32 coexpression with HIV RNA or p24 was detected after in vitro HIV infection (peripheral blood mononuclear cell and tissue) and in vivo within lymph node tissue from HIV-infected individuals. Together, these results indicate that CD32 is not a marker of resting CD4+ T cells or of enriched HIV DNA-positive cells after ART; rather, CD32 is predominately expressed on a subset of activated CD4+ T cells enriched for transcriptionally active HIV after long-term ART.