tbuckley/cabot-search huggingface dataset:
Abstract 16819: Intracellular Dyssynchrony in Ca Removal from the Cytosol In Ventricular Cardiac Myocytes
Authors: Felix Hohendanner, Niall McQuaide, Gudrun Antoons, Karin Sipido, Burkert Pieske, Frank R Heinzel
Journal: Circulation (2011)

In cardiomyocytes, cytosolic Ca removal is mediated by the sarcoplasmic reticulum Ca ATPase (SERCA), sarcolemmal Na/Ca exchanger (NCX), plasmalemmal Ca ATPase and mitochondrial Ca uniporter (MCU). We report, for the first time, spatiotemporal inhomogeneities in cytosolic Ca removal in normal and diseased heart and explore underlying mechanisms. Spatially resolved Ca transients (1 Hz, Fluo-4 AM) were recorded at steady state using confocal microscopy in ventricular cardiomyocytes. The time constant of cytosolic [Ca] decay (tau_loc) of local Ca transients was quantified at 1 µm intervals across the cell. In murine cardiomyocytes tau_loc distribution was inhomogeneous, with a maximal difference between cell regions of 237±9 ms and a variation coefficient (CV_tau) of 14±2% (mean±S.E.M., n=10 cells). tau_loc was not releated to the local amplitude or release kinetics of Ca. Coherent regions of fast (fastCaR, tau_loc &lt; mean tau of whole cell) and slow (slowCaR) Ca removal had similar widths (4.6±0.2 vs. 5.1±0.5 µm). Forskolin accelerated, and SERCA inhibitor cyclopiazonic acid (CPA) inhibited Ca removal significantly more in slowCaR than in fastCaR. In contrast, NCX-inhibitor SEA0400 slowed cytosolic Ca removal similarly in slowCaR and fastCaR. Also, CV_tau was similar in NCX+/- knock-out vs. wild-type mice, suggesting no contribution of NCX to the dyssynchrony of cytosolic Ca removal. tau_loc distribution was also inhomogenous in pig ventricular myocytes. Ca removal from the cytosol was more dyssynchronous in cardiomyocytes from chronic (4 weeks) ischemic pig myocardium (peri-infarct zone) vs. sham-operated pigs (CV_tau 24±1% vs. 20±1%, n=57 cells/group, p&lt;0.05). Simultaneous recording of Ca transients and mitochondrial signal (mitotracker) unveiled a significant correlation between FastCaR regions and mitochondria (n=9 cells, p&lt;0.05). Ru360 (MCU-inhibitor) slowed tau_loc more in FastCaR (to 126±12% vs. 112±10% of baseline in SlowCaR; p&lt;0.05, n=5). Conclusion: Cytosolic Ca removal is dyssynchronous in mouse and pig cardiomyocytes. Ca removal in chronically ischemic cardiomyocytes is more dyssynchronous, suggesting a potential new mechanism of cardiomyocyte dysfunction. Mitochondria influence the differences in local Ca reuptake.
Fiber scaffold bioartificial liver therapy relieves acute liver failure and extrahepatic organ injury in pigs
Authors: Jun Weng, Xu Han, Fanhong Zeng, Yue Zhang, Lei Feng, Lei Cai, Kangyan Liang, Shusong Liu, Shao Li, Gongbo Fu, Min Zeng, Yi Gao
Journal: Theranostics (2021)

Acute liver failure (ALF) causes severe liver injury and a systemic inflammatory response, leading to multiorgan failure with a high short-term mortality. Bioartificial liver (BAL) therapy is a promising approach that is hampered by the lack of appropriate bioreactors and carriers to retain hepatic cell function and poor understanding of BAL treatment mechanisms in ALF and extrahepatic organ injury. Recently, we used a fiber scaffold bioreactor (FSB) for the high-density, three-dimensional (3D) culture of primary porcine hepatocytes (PPHs) combined with an absorption component to construct a BAL and verified its function in a D-galactosamine (D-gal)-induced ALF porcine model to evaluate its protective effects on the liver and extrahepatic organs.
Deficits in Geriatric Assessment Associate With Disease Activity and Burden in Older Patients With Inflammatory Bowel Disease
Authors: Vera E.R. Asscher, Sanne N. Waars, Andrea E. van der Meulen-de Jong, Rogier J.L. Stuyt, A. Martine C. Baven-Pronk, Sander van der Marel, Rutger J. Jacobs, Jeoffrey J.L. Haans, Lennart J. Meijer, Jacqueline D. Klijnsma-Slagboom, Marijn H. Duin, Milou E.R. Peters, Felicia V.Y.L. Lee-Kong, Nanda E. Provoost, Femke Tijdeman, Kenan T. van Dijk, Monse W.M. Wieland, Mirre G.M. Verstegen, Melissa E. van der Meijs, Annemijn D.I. Maan, Floor J. van Deudekom, Simon P. Mooijaart, P.W. Jeroen Maljaars
Journal: Clinical Gastroenterology and Hepatology (2021)
Анатомічний театр Університету святого Володимира (До 160-річчя з дня відкриття)
Authors: V.P. Shypulin, V.D. Doguzov
Journal: GASTROENTEROLOGY (2013)

У статті висвітлено історію створення та розвитку Анатомічного театру Університету св. Володимира як значного навчального та науково-дослідного закладу, на базі якого вченими декількох кафедр у другій половині ХІХ — на початку ХХ ст. було зроблено низку відкриттів світового значення. Наведені передумови заснування, основні етапи розвитку та зміни функціонального призначення закладу.
Leukocytoclastic Vasculitis After Vaccination With a SARS‐CoV‐2 Vaccine
Authors: Anne Erler, John Fiedler, Anna Koch, Frank Heldmann, Alexander Schütz
Journal: Arthritis & Rheumatology (2021)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Trajectories of asthma and allergies from 7 to 53 years and their relationship with middle-aged lung function and extra-pulmonary comorbidity profiles: a prospective cohort study
Authors: Dinh Bui, Caroline Lodge, Jennifer Perret, Adrian Lowe, Garun Hamilton, Bruce Thompson, Graham Giles, Bircan Erbas, Jane Pirkis, Flavia Cicutini, Raisa Cassim, Gayan Bowatte, Paul Thomas, John Hopper, Michael Abramson, Haydn Walters, Shyamali Dharmage
Journal: The Lancet Respiratory Medicine (2021)
ATR Inhibition Induces CDK1–SPOP Signaling and Enhances Anti–PD-L1 Cytotoxicity in Prostate Cancer
Authors: Zhe Tang, Patrick G. Pilié, Chuandong Geng, Ganiraju C. Manyam, Guang Yang, Sanghee Park, Daoqi Wang, Shan Peng, Cheng Wu, Guang Peng, Timothy A. Yap, Paul G. Corn, Bradley M. Broom, Timothy C. Thompson
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Despite significant benefit for other cancer subtypes, immune checkpoint blockade (ICB) therapy has not yet been shown to significantly improve outcomes for men with castration-resistant prostate cancer (CRPC). Prior data have shown that DNA damage response (DDR) deficiency, via genetic alteration and/or pharmacologic induction using DDR inhibitors (DDRi), may improve ICB response in solid tumors in part due to induction of mitotic catastrophe and innate immune activation. Discerning the underlying mechanisms of this DDRi–ICB interaction in a prostate cancer–specific manner is vital to guide novel clinical trials and provide durable clinical responses for men with CRPC. Experimental Design: We treated prostate cancer cell lines with potent, specific inhibitors of ATR kinase, as well as with PARP inhibitor, olaparib. We performed analyses of cGAS–STING and DDR signaling in treated cells, and treated a syngeneic androgen-indifferent, prostate cancer model with combined ATR inhibition and anti–programmed death ligand 1 (anti–PD-L1), and performed single-cell RNA sequencing analysis in treated tumors. Results: ATR inhibitor (ATRi; BAY1895433) directly repressed ATR–CHK1 signaling, activated CDK1–SPOP axis, leading to destabilization of PD-L1 protein. These effects of ATRi are distinct from those of olaparib, and resulted in a cGAS–STING-initiated, IFN-β–mediated, autocrine, apoptotic response in CRPC. The combination of ATRi with anti–PD-L1 therapy resulted in robust innate immune activation and a synergistic, T-cell–dependent therapeutic response in our syngeneic mouse model. Conclusions: This work provides a molecular mechanistic rationale for combining ATR-targeted agents with immune checkpoint blockade for patients with CRPC. Multiple early-phase clinical trials of this combination are underway.
Hypersensitivity reactions to biologicals: An EAACI position paper
Authors: Sevim Bavbek, Mauro Pagani, Emilio Alvarez‐Cuesta, Mariana Castells, Adile Berna Dursun, Sahar Hamadi, Ricardo Madrigal‐Burgaleta, Soledad Sanchez‐Sanchez, Alessandra Vultaggio
Journal: Allergy (2021)

Biologicals are crucial targeted therapeutic agents in oncological, immunological, and inflammatory diseases, and their use in clinical practice is broadening. In recent years, the spread of Personalized Precision Medicine has facilitated a proliferation of new treatment options, especially biologicals. Consequently, biologicals are now among the drugs that most frequently cause hypersensitivity reactions (HSRs). Patients can develop HSRs to these agents during the first-lifetime exposure or after repeated exposure, and these HSRs can be potentially life-threatening or limit therapeutic options. Despite the relatively high prevalence, the underlying mechanisms of these HSRs remain obscure, and the optimal management pathways are still a matter of discussion. In this Position Paper, the authors will provide evidence-based recommendations for diagnosing and managing HSRs to biologicals. Additionally, the document defines unmet needs as an opportunity to shape future research.
Heme Oxygenase-1 Protects Bone Marrow Mesenchymal Stem Cells Against Iron Overload through Decreasing ROS and Promoting IL-10 Generation
Authors: Zhengyu Yu, Dan Ma, Zhengchang He, Ping Liu, Jun Huang, Qin Fang, Jiangyuan Zhao, Jishi Wang
Journal: Blood (2017)
Assessing factors associated with COVID19 risk in asthma
Authors: C. I. Bloom, P. Cullinan, J. A. Wedzicha
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

RATIONALE Several factors may be associated with the apparent reduced risk of severe COVID-19 disease in asthma patients. These include a proposed protective effect from inhaled corticosteroids (ICS) or from a type-2 immune airway response. Large UK population cohorts have found conflicting results, but each had missing information on asthma phenotype, including exacerbation history or markers of type-2 inflammation. Protective factors may be determined by comparing the outcomes of asthma patients to other patients using ICS or patients that have similar inflammation. This will be done using a national primary care database linked to secondary care data and Public Health England (PHE) COVID-19 data. METHODS From a primary care database covering around 15% of the UK population, we drew three cohorts of adults (>17 years) with asthma, chronic obstructive pulmonary disease (COPD) or allergic rhinitis, and a general population cohort matched by age, gender and primary care practice. COVID-19 infection was defined using three sources: primary care records (confirmed and suspected cases), hospital admissions or PHE data from their surveillance system. Preliminary analysis calculated the proportion of patients diagnosed as suspected or confirmed COVID-19 in primary care between 1st February and 22nd June 2020. We used multivariable logistic regression to assess associations between risk factors and COVID-19. RESULTS We identified 729,045 patients with asthma, 280,892 with COPD, 137,312 with allergic rhinitis and 1,138,018 in the general population cohort. 2.2% of the asthma cohort, 3.5% the COPD cohort, 2.4% of the allergic rhinitis cohort and 1.1% of the general population, were identified as having either suspected or confirmed COVID-19 in primary care (approximately a quarter were confirmed). In the asthma cohort, the following were found to be independently significantly associated with having suspected/confirmed COVID-19;older age, being male, diabetes, cardiovascular disease, obesity, sleep apnoea, bronchiectasis, COPD, ILD, chronic renal failure, cerebrovascular disease, dementia and liver disease (all p<0.0001). A history of past or current smoking and a high eosinophil count were not significantly associated. CONCLUSIONS These preliminary findings suggest patients with asthma are more likely to consult primary care about COVID-19 than a matched general population, but less likely than COPD patients, and that type-2 inflammation may not be associated with an increased risk of COVID-19 consultation with a primary care physician. Analysis comparing to the other cohorts and the general population, and using data from secondary care and PHE, is ongoing.
Antibodies from malaria-exposed Malians generally interact additively or synergistically with human vaccine-induced RH5 antibodies
Authors: Alexandra C. Willcox, Alex S. Huber, Ababacar Diouf, Jordan R. Barrett, Sarah E. Silk, David Pulido, Lloyd D.W. King, Daniel G.W. Alanine, Angela M. Minassian, Mahamadou Diakite, Simon J. Draper, Carole A. Long, Kazutoyo Miura
Journal: Cell Reports Medicine (2021)

<h2>Summary</h2> Reticulocyte-binding protein homolog 5 (RH5) is a leading <i>Plasmodium falciparum</i> blood-stage vaccine candidate. Another possible candidate, apical membrane antigen 1 (AMA1), was not efficacious in malaria-endemic populations, likely due to pre-existing antimalarial antibodies that interfered with the activity of vaccine-induced AMA1 antibodies, as judged by <i>in vitro</i> growth inhibition assay (GIA). To determine how pre-existing antibodies interact with vaccine-induced RH5 antibodies, we purify total and RH5-specific immunoglobulin Gs (IgGs) from malaria-exposed Malians and malaria-naive RH5 vaccinees. Infection-induced RH5 antibody titers are much lower than those induced by vaccination, and RH5-specific IgGs show differences in the binding site between the two populations. In GIA, Malian polyclonal IgGs show additive or synergistic interactions with RH5 human monoclonal antibodies and overall additive interactions with vaccine-induced polyclonal RH5 IgGs. These results suggest that pre-existing antibodies will interact favorably with vaccine-induced RH5 antibodies, in contrast to AMA1 antibodies. This study supports RH5 vaccine trials in malaria-endemic regions.
Abstract 16326: A Multi-Marker Approach for the Prediction of Adverse Events in Patients with Acute Myocardial Infarction
Authors: Byung-Su Yoo, Ji-Hyun Lee, Jun-Won Lee, Young-Jin Youn, Sung Gyun Ahn, Seung-Hwan Lee, Junghan Yoon, Myeong-Chan Cho, Young Keun Ahn, Shung Chull Chae
Journal: Circulation (2012)

Background: Cardiac troponin I (cTnI), high sensitivity C-reactive protein (hsCRP), serum creatinine (sCr) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) have emerged as strong predictor...
Abstract 294: Therapeutic Silencing of miR-375 Attenuates Post-MI Inflammatory Response and Left Ventricular Dysfunction in Mice With Myocardial Infarction
Authors: Venkata N Garikipati, Suresh K Verma, Darukeshwara Jolardarashi, Maria Cimini, Jessica Ibetti, Yujia Yue, Cindy Benedict, Emily Nickoloff, Ehre Gao, Prasanna Krishnamurthy, Walter J Koch, Raj Kishore
Journal: Circulation Research (2016)

MicroRNAs are known to be dysregulated in the ischemic heart disease and have emerged as potential therapeutic targets for treatment of myocardial infarction (MI). Our preliminary data indicated elevated MicroRNA-375 levels in failing human heart tissue. Therefore, we assessed whether inhibition of the miR-375 using a s.c.-delivered locked nucleic acid (LNA)-modified anti-miR (LNA-antimiR-375) can provide therapeutic benefit in mice with myocardial infarction (MI). After the induction of acute myocardial infarction, mice were treated with either control or LNA based LNA-anti-miR-375, and inflammatory response, cardiomyocyte apoptosis, capillary density and LV functional and structural remodeling changes were evaluated. LNA-anti-miR-375 therapy significantly reduced inflammatory cell infiltration, expression of pro-inflammatory cytokines and cardiomyocyte apoptosis in the myocardium. Further, our cell sorting experiments revealed that within the myocardium, LNA-anti-miR-375 was taken up by cardiomyocytes, endothelial cells and macrophages and repressed miR-375 levels, thereby activating 3-phosphoinositide-dependent protein kinase 1 (PDK-1) and downstream AKT phosphorylation on Thr-308. LNA anti-miR-375 therapy significantly improved LV functions, enhanced neovascularization and reduced infarct size. Corroborating with our in vivo findings, our in vitro studies demonstrated that knock down of miR-375 in macrophages enhanced the expression of PDK-1 and revealed reduced pro-inflammatory cytokines expression following LPS challenge. Taken together, our studies demonstrate that anti miR-375 therapy reduced inflammatory response, cardiomyocyte death, improved LV function and enhanced angiogenesis by targeting multiple cell types via activation of PDK-1/AKT signaling.
BNT162b2 COVID-19 vaccine and correlates of humoral immune responses and dynamics: a prospective, single-centre, longitudinal cohort study in health-care workers
Authors: Yaniv Lustig, Einav Sapir, Gili Regev-Yochay, Carmit Cohen, Ronen Fluss, Liraz Olmer, Victoria Indenbaum, Michal Mandelboim, Ram Doolman, Sharon Amit, Ella Mendelson, Arnona Ziv, Amit Huppert, Carmit Rubin, Laurence Freedman, Yitshak Kreiss
Journal: The Lancet Respiratory Medicine (2021)
Rectal neuroendocrine tumors: is it all on first sight?
Authors: Louis de Mestier, Guillaume Cadiot
Journal: Endoscopy (2021)

The incidence of rectal neuroendocrine tumors (NETs) has been steadily rising during recent decades, reaching approximately 1.2 /100 000 per year in 2012 [1]. This is notably due to the increasing number of colonoscopies performed, with a prevalence of rectal NETs of about 0.17 % in adults undergoing screening colonoscopy [2]. As a consequence, all endoscopists face situations of the per-procedure discovery of a rectal polyp evocative of a rectal NET, or will face it during their activity.
Efficacy of under-gel endoscopic mucosal resection method for colonic lesion extending into the diverticulum
Authors: Hiroki Kuwabara, Hideyuki Chiba, Jun Tachikawa, Naoya Okada, Jun Arimoto, Michiko Nakaoka
Journal: Endoscopy (2021)

Underwater endoscopic mucosal resection (EMR) is currently performed in various situations [1] [2] [3] [4]. One advantage to using water is the buoyancy effect on the mucosa, which raises it from the deeper muscularis propria without submucosal injection [1]. However, it takes time to fill the intestinal tract with water, leading to an increased risk of peristalsis and abdominal distension. In addition, underwater EMR on lesions extending into narrow spaces can be difficult to snare because constant water pressure is required. Here, we present a case in which a colonic adenoma extending into the diverticulum was successfully resected using "under-gel EMR" via VISCOCLEAR, a gel product for endoscopic procedures (Otsuka Pharmaceutical Factory, Tokushima, Japan).
Platelet Desialylation Is a Novel Mechanism of Thrombocytopenia during Mechanical Circulatory Assistance
Authors: Hugues Spillemaeker, Annabelle Dupont, Alexandre Kauskot, Antoine Rauch, Flavien Vincent, Delphine Borgel, Alexandre Ung, Mouhamed Moussa, Natacha Rousse, Christophe Nix, Bart Staels, André Vincentelli, Cecile V. Denis, Peter J Lenting, Eric van Belle, Sophie Susen
Journal: Blood (2017)
High Risk of Fractures Within 7 Years of Diagnosis in Asian Patients With Inflammatory Bowel Diseases
Authors: Hyung Jin Ahn, Ye-Jee Kim, Ho-Su Lee, Jin Hwa Park, Sung Wook Hwang, Dong-Hoon Yang, Byong Duk Ye, Jeong-Sik Byeon, Seung-Jae Myung, Suk-Kyun Yang, Beom-Jun Kim, Sang Hyoung Park
Journal: Clinical Gastroenterology and Hepatology (2021)
Titanium carbide nanosheets with defect structure for photothermal-enhanced sonodynamic therapy
Authors: Guangqiang Li, Xiaoyan Zhong, Xianwen Wang, Fei Gong, Huali Lei, Yangkai Zhou, Chengfei Li, Zhidong Xiao, Guoxi Ren, Liang Zhang, Zhiqiang Dong, Zhuang Liu, Liang Cheng
Journal: Bioactive Materials (2021)

Sonodynamic therapy (SDT) has attracted widespread interest in biomedicine, owing to its novel and noninvasive therapeutic method triggered by ultrasound (US). Herein, the Ti3C2 MXene nanosheets (Ti3C2 NSs) are developed as good sonosensitizers via a two-step method of chemical exfoliation and high-temperature treatment. With the high-temperature treatment, the oxygen defect of Ti3C2 MXene nanosheets (H–Ti3C2 NSs) is greatly increased. Therefore, the electron (e−) and hole (h+) generated by US can be separated faster due to the improved degree of oxidation, and then the recombination of e−-h+ can be prevented with the abundant oxygen defect under US irradiation, which induced the sonodynamic efficiency greatly to improve around 3.7-fold compared with Ti3C2 NSs without high-temperature treatment. After PEGylation, the H–Ti3C2-PEG NSs show good stability and biocompatibility. In vitro studies exhibit that the inherent property of mild photothermal effect can promote the endocytosis of H–Ti3C2-PEG NSs, which can improve the SDT efficacy. In vivo studies further display that the increased blood supply by the mild photothermal effect can significantly relieve hypoxia in the tumor microenvironment, showing photothermal therapy (PTT) enhanced SDT. Most importantly, the H–Ti3C2-PEG NSs can be biodegraded and excreted out of the body, showing no significant long-term toxicity. Our work develops the defective H–Ti3C2 NSs as high-efficiency and safe sonosensitizers for photothermal-enhanced SDT of cancer, extending the biomedical application of MXene-based nanoplatforms.
進行性固形腫瘍(ST)を呈する患者(pts)におけるペメトレキセド(Pem)併用のスニチニブ(SU)の第I相研究
Authors: Kiriyama T, Fumita S, Takeda M, Terashima M, Ichikawa Y, Tsurutani J, Miyazaki M, Shimizu T, Okamoto I, Nakagawa K
Journal: Journal of Thoracic Oncology (2009)
Abstract 124: Integrated Omics Approaches to Elucidate Targets of Cyclic AMP-Epac-Rap1A Signaling in Microvascular Smooth Muscle Cells: Identification of Role in Production and Deposition of Extracellular Matrix Fibrillar Collagen
Authors: Maqsood A Chotani
Journal: Circulation Research (2016)

Objective: Intracellular signaling by cyclic AMP (cAMP) has an essential role in vascular smooth muscle (VSM) physiology, including relaxation of large blood vessels such as aorta and pulmonary artery. Studies support a mechanism of signaling through e xchange p rotein a ctivated by c AMP (epac) and Ras-related small GTPase Rap1B down-regulation of RhoA activity. The role of cAMP in small blood vessels however was not examined, and remained unknown. This study elucidated the targets of cAMP signaling in peripheral blood vessels, specifically VSM explanted from healthy human (h) cutaneous arterioles and mouse (m) tail artery (microVSM). Results: Global changes in protein expression were assessed by Differential-in-Gel Electrophoresis in quiescent (h)-microVSM treated with the adenylate cyclase activator and cAMP elevating agent forskolin (10 μM, 30 min or 18 hr). Detectable changes were observed in proteins associated with the cytoskeleton, stress-response, protein-synthesis, -folding, -membrane transport, and extracellular matrix. Notably, actin modulating proteins caldesmon, ezrin-moesin, zyxin, gelsolin, and α-adducin, as well as cytoskeletal proteins, tubulin and vimentin were differentially expressed ( P&lt; 0.05; 3-5 replicates). These results agreed with our recent demonstration of cAMP activation of epac-Rap1A, and RhoA-ROCK-F-actin signaling in (h)- and (m)-microVSM to increase expression and cell surface transport of functional α 2C -adrenoceptors (α 2C -ARs) that mediate vasoconstriction. Transcriptome analysis of Rap1A-null (knockout) (m)-microVSM transduced with constitutively active Rap1A showed connections to signaling linked to vessel production and deposition of extracellular matrix fibrillar collagen, compared with control cells ( P&lt; 0.05, 4 replicates). Conclusions: Rap1 subtypes have a discrete role in the vasculature. This study links cAMP-Rap1A signaling to collagen and α 2C -AR expression in arteriole VSM. It suggests over-activation of Rap1A-coupled signaling in the peripheral circulation during chronic inflammation could lead to increased α 2C -AR mediated vessel reactivity, progressive perivascular fibrosis, and dysfunction as seen in human pathologies such as Raynaud’s phenomenon and scleroderma.