tbuckley/cabot-search huggingface dataset:
Bio‐Conductive Polymers for Treating Myocardial Conductive Defects: Long‐Term Efficacy Study
Authors: Anne Fu, Yahan Yang, Jun Wu, Shu‐Hong Li, Yunfei Fan, Terrance M Yau, Ren‐Ke Li
Journal: Advanced Healthcare Materials (2021)

Following myocardial infarction (MI), the resulting fibrotic scar is nonconductive and leads to ventricular dysfunction via electrical uncoupling of the remaining viable cardiomyocytes. The uneven conductive properties between normal myocardium and scar tissue result in arrhythmia, yielding sudden cardiac death/heart failure. A conductive biopolymer, poly-3-amino-4-methoxybenzoic acid-gelatin (PAMB-G), is able to resynchronize myocardial contractions in vivo. Intravenous PAMB-G injections into mice show that it does not cause any acute toxicity, up to the maximum tolerated dose (1.6 mL kg-1 ), which includes the determined therapeutic dose (0.4 mL kg-1 ). There is also no short- or long-term toxicity when PAMB-G is injected into the myocardium of MI rats, with no significant changes in body weight, organ-brain ratio, hematologic, and histological parameters for up to 12 months post-injection. At the therapeutic dose, PAMB-G restores electrical conduction in infarcted rat hearts, resulting in lowered arrhythmia susceptibility and improved cardiac function. PAMB-G is also durable, as mass spectrometry detected the biopolymer for up to 12 months post-injection. PAMB-G did not impact reproductive organ function or offspring characteristics when given intravenously into healthy adult rats. Thus, PAMB-G is a nontoxic, durable, and conductive biomaterial that is able to improve cardiac function for up to 1 year post-implantation.
CHARM IN-VESTIGATORS AND COMMITTEES. EFFECTS OF CANDESARTAN IN PATIENTS WITH CHRONIC HEART FAILURE AND REDUCED LEFT-VENTRICULAR SYSTOLIC FUNCTION TAKING ANGIOTENSIN-CONVERTING-ENZYME INHIBITORS: THE CHARM-ADDED TRIAL
Authors: J J Mcmurray, J Ostergren, K Swedberg, C B Granger, P Held, E L Michelson, B Olofsson, S Yusuf, Pfeffer
Journal: The Lancet (2003)
Use of Peritoneal Dialysis for the Treatment of AKI Was Associated with Lower Risk for 30-Day All-Cause Mortality During the COVID-19 Surge
Authors: Maryanne Sourial, Anirudh R. Gone, Jaime Uribarri, Nina J. Caplin, Vesh Srivatana, Shuchita Sharma, Daniil Shimonov, Michael Chang, Wenzhu Mowrey, Rochelle Dalsan, Kaltrina Sedaliu, Swati Jain, Michael J. Ross, Wei Chen
Journal: Journal of the American Society of Nephrology (2021)

Background: To offset resource constraints that limited the capability to deliver hemodialysis (HD) during the COVID-19 surge, nephrologists in New York City (NYC) rapidly incorporated peritoneal dialysis (PD) for the treatment of acute kidney injury (AKI), which was rarely used in the United States. This study aims to compare the in-hospital all-cause mortality between AKI patients who received PD versus HD during the COVID-19 pandemic. Methods: In a retrospective observational study, we collected data on 259 patients with AKI who required kidney replacement therapy (KRT) in four medical centers of NYC during the Spring 2020. Patients who had ever received PD were included in the PD group (n=93), and patients who only received intermittent HD or continuous KRT were included in the HD group (n=166). Kaplan-Meier survival curves, log-rank test and Cox regression were used to compare survival between PD and HD groups. Results: For the entire cohort, the mean age was 61±11 years;31% were women;96% had confirmed COVID-19. Median follow up was 21 days (IQR 12-30). Mortality was lower in PD group compared to HD group (43% vs. 60%, p=0.01). Time-dependent analyses showed that PD group was at a lower risk for mortality compared to HD group (p<0.001 for Log-rank test;Figure). After adjusting for age, sex, BMI, comorbidities, oxygenation on admission, mechanical ventilation, prone positioning, steroid use and C-reactive protein, the PD group remained to have a lower risk of mortality compared to the HD group with a HR of 0.45 (95% CI: 0.27-0.77, p=0.003). Conclusions: Compared to HD, the use of PD for the treatment of AKI was associated with lower mortality in this cohort of patients treated during the COVID-19 pandemic in the Spring of 2020. Our findings demonstrate that rapid implementation of PD for the treatment of AKI was feasible and may be lifesaving.
Measurement of IgE to hazelnut allergen components cannot replace hazelnut challenge in Dutch adults
Authors: Sarah A. Lyons, Paco M. J. Welsing, Mariam Hakobyan, Hannah M. Kansen, Edward F. Knol, Henny G. Otten, Ronald van Ree, André C. Knulst, Thuy‐My Le
Journal: Allergy (2021)

Component-resolved diagnostics (CRD) help predict hazelnut allergy (HA) in children, but are of unknown diagnostic value in adults. This study aimed to evaluate the diagnostic accuracy of IgE to hazelnut extract and components in adults.A Dutch population of consecutively presenting adults suspected of HA, who underwent a double-blind placebo-controlled food challenge, were included. Serum IgE to hazelnut extract and Cor a 1, 8, 9, and 14 was measured on ImmunoCAP. Diagnostic accuracy was assessed by area under the curve (AUC) analysis.Of 89 patients undergoing challenge, 46 had challenge-confirmed HA: 17 based on objective and 29 based on subjective symptoms. At commonly applied cutoffs 0.1 and 0.35 kUA /L, high sensitivity was observed for IgE to hazelnut extract and Cor a 1 (range 85-91%), and high specificity for IgE to Cor a 8, 9 and 14 (range 77-95%). However, the AUCs for hazelnut extract and components were too low for accurate prediction of HA (range 0.50-0.56). Combining hazelnut extract and component IgE measurements did not significantly improve accuracy. Higher IgE levels to Cor a 9 and 14 were tentatively associated with HA with objective symptoms, but the corresponding AUCs still only reached 0.68 and 0.63, respectively.Although hazelnut allergic adults are generally sensitized to hazelnut extract and Cor a 1, and hazelnut tolerant adults are usually not sensitized to Cor a 8, 9, or 14, challenge testing is still needed to accurately discriminate between presence and absence of HA in adults from a birch-endemic country.
Akt inhibitor induces apoptosis in human cancer cells
Authors: Zhao Hai Lu, Sophie Boguslawski, Lori Johnson, Jianping Huang, Philip Waid, Sajan Joseph, Mei Lai
Journal: Cancer Research (2007)

2560  Phosphoinositide 3-OH kinase (PI3-K) and its downstream target, Akt mediate one of the most important survival signaling pathways in cancer cells. The mechanism by which PI3-K/Akt pathway affects cell survival is through its downstream target proteins such as BAD, Caspase-9, Forkhead transcription factors, IKKα and TSC1/2. Therefore, inhibition of Akt activity is expected to induce apoptotic cell death at multiple levels. In addition, down-regulation of Akt signaling pathway may sensitize cancer cells to cytotoxic oncolytics. There are enormous clinical advantages in exploring this cell survival pathway. This makes Akt among the most validated and attractive targets for the discovery of efficacious therapeutics for the treatment of human cancers. Here we report that isoquinoline sulfonamide-based Akt kinase inhibitors exert potent anti-proliferative effect on U87MG human glioblastoma cells and Jurkat human T-cell leukemia cells. Both cell lines are PTEN-null with constitutively activated Akt. We further demonstrate that these AKT inhibitors induce a robust Caspases activation and rapid phosphatidyl serine (PS) exposure on cell surface, characteristic of cells undergoing rapid apoptosis. Data will also be presented to show that down-regulation of Akt activity either by Akt-specific siRNA or small molecule inhibitors sensitize cancer cells to various oncolytics such as Gemcitabine, Camptothecin and Dexamethasone, as well as TRAIL. We conclude that treatment of U87MG and Jurkat cells with isoquinoline sulfonamide class of Akt inhibitor results in apoptotic cell death. And these results support the notion that synergistic anticancer action can be achieved by combination therapy using Akt inhibitors and conventional cytotoxic cancer therapeutics.
Fe(III)‐Shikonin Supramolecular Nanomedicine for Combined Therapy of Tumor via Ferroptosis and Necroptosis
Authors: Wenjie Feng, Wanrui Shi, Shuwei Liu, Huiwen Liu, Yi Liu, Pengfei Ge, Hao Zhang
Journal: Advanced Healthcare Materials (2021)

Most of the antitumor chemotherapeutic drugs execute the therapeutic performance upon eliciting tumor cell apoptosis, which may cause chemoresistance of tumors. Design of novel drugs to eradicate apoptosis-resistant tumors via non-apoptotic cell death pathways is promising for improving the long-term chemotherapeutic efficacy. Herein, a Fe(III)-Shikonin metal-polyphenol-coordinated supramolecular nanomedicine for combined therapy of tumor via ferroptosis and necroptosis is designed. The construction of the nanomedicine based on the coordinated self-assembly between Fe3+ and Shikonin not only overcomes the shortcomings of Shikonin including its low bioavailability and high toxicity toward normal tissues, but also integrates the theranostics functions of Fe ions. Under the exposure of the high concentration of glutathione (GSH) in tumor cells, the as-prepared nanomedicine will disassemble into Fe2+ and Shikonin, followed by stimulating the tumor cell death through ferroptosis and necroptosis. In addition, benefiting from the stealth effect of polyethylene glycol (PEG) and the targeting ability of cyclo(Arg-Gly-Asp-d-Phe-Lys) (cRGD) to αv β3 -integrin, NH2 -PEG-cRGD-modified nanomedicine exhibits a GSH-responsive therapy toward 4T1 tumor in vivo and self-enhanced longitudinal relaxation (T1 )-weighted imaging property. Since the self-assembly of natural Shikonin and human body-necessary Fe element is facile and feasible, the work may provide a promising supramolecular nanomedicine for next-generation chemotherapeutic applications.
COMPERA 2.0: a refined four-stratum risk assessment model for pulmonary arterial hypertension
Authors: Marius M. Hoeper, Christine Pausch, Karen M. Olsson, Doerte Huscher, David Pittrow, Ekkehard Grünig, Gerd Staehler, Carmine Dario Vizza, Henning Gall, Oliver Distler, Christian Opitz, J. Simon R. Gibbs, Marion Delcroix, H. Ardeschir Ghofrani, Da-Hee Park, Ralf Ewert, Harald Kaemmerer, Hans-Joachim Kabitz, Dirk Skowasch, Juergen Behr, Katrin Milger, Michael Halank, Heinrike Wilkens, Hans-Jürgen Seyfarth, Matthias Held, Daniel Dumitrescu, Iraklis Tsangaris, Anton Vonk-Noordegraaf, Silvia Ulrich, Hans Klose, Martin Claussen, Tobias J. Lange, Stephan Rosenkranz
Journal: European Respiratory Journal (2021)

Risk stratification plays an essential role in the management of patients with pulmonary arterial hypertension (PAH). The current European guidelines propose a three-stratum model to categorise risk as low, intermediate or high, based on the expected 1-year mortality. However, with this model, most patients are categorised as intermediate risk. We investigated a modified approach based on four risk categories, with intermediate risk subdivided into intermediate-low and intermediate-high risk.We analysed data from the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA), a European pulmonary hypertension registry, and calculated risk at diagnosis and first follow-up based on World Health Organization functional class, 6-min walk distance (6MWD) and serum levels of brain natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP), using refined cut-off values. Survival was assessed using Kaplan-Meier analyses, log-rank testing and Cox proportional hazards models.Data from 1655 patients with PAH were analysed. Using the three-stratum model, most patients were classified as intermediate risk (76.0% at baseline and 63.9% at first follow-up). The refined four-stratum risk model yielded a more nuanced separation and predicted long-term survival, especially at follow-up assessment. Changes in risk from baseline to follow-up were observed in 31.1% of the patients with the three-stratum model and in 49.2% with the four-stratum model. These changes, including those between the intermediate-low and intermediate-high strata, were associated with changes in long-term mortality risk.Modified risk stratification using a four-stratum model based on refined cut-off levels for functional class, 6MWD and BNP/NT-proBNP was more sensitive to prognostically relevant changes in risk than the original three-stratum model.
Increased expression and activity of Akt in primary ductal breast cancers and activation of the ErbB2/Akt/ER- α pathway
Authors: Adriana Stoica, Molly Proskine, Rebecca Slack, Ying Qiu Chen, Jennifer Fagel, Emily Wang, Robert Russell
Journal: Cancer Research (2007)

3575  Introduction: We have previously demonstrated that Akt1 is activated not only by epidermal growth factor (EGF), insulin-like growth factor I (IGF-I), and heregulin-β1 (HRG-β1), but also by estradiol. This cross-talk between growth factors and estrogen receptor-α (ER-α) signaling converges in the EGF receptor family member, ErbB2 / phosphatidylinositol 3-kinase PI 3-K/serine/threonine protein kinase Akt pathway in hormone-dependent MCF-7 breast cancer cells in vitro and xenografts grown in vivo. The aim of the present study was to investigate whether the current model of this tumorigenic pathway is active in clinical breast cancer.  Methods: We analyzed the expression levels of Akt1 and phosphorylated Akt (pAkt) by immunohistochemistry and western blot analysis in pairs of frozen tumor samples and their corresponding matched normal adjacent lobular breast tissue from 58 breast cancer patients. These patients did not have a previous history of therapeutic intervention. The tumors were mostly invasive, high grade, ductal carcinomas, with an approximately equal distribution of ER-α, ErbB2, and lymph node positivity. Spearman’s rank correlations were calculated for Akt expression and phosphorylation, measured by either immunohistochemistry or western blot, and patient and clinical-pathological tumor classification.  Results: Marked staining was observed for Akt1 in 98% of the tumors and pAkt was expressed in 83%. Akt1 was localized mostly in the cytoplasm, but also in the nucleus. Normal tissues revealed much less staining for Akt1 and pAkt than tumor tissue, also with more cytoplasmic localization and less nuclear staining. Nuclear Akt1 measured by immunohistochemistry was highly correlated with Akt1 expression measured by western blot analysis (Akt-WB) (p=0.04), cytoplasmic Akt1 (cyt Akt) (p=0.006), and nuclear pAkt (p=0.003). Additionally, nuclear pAkt was highly correlated with phosphorylated cytoplasmic Akt (cyt pAkt) (p=0.001). Akt1 and pAkt expression were not significantly correlated with age, tumor type, nuclear grade, lymph node positivity, progesterone receptor (PR), or the proliferation rate, Ki67. Nuclear Akt1 and cyt pAkt were each significantly correlated with tumor size (p=0.02). Cyt pAkt was positively correlated with histological grade (p=0.02) and inversely correlated with ER-α status (p=0.04) and with ErbB2 expression (p=0.05). Nuclear pAkt was also inversely correlated with ErbB2 (p=0.04). pAkt measured by western blot (pAkt-WB) was also associated with tumor size (p=0.03).  Conclusion: Similar to our in vitro model and animal data, in invasive, high grade, ductal carcinomas, Akt expression and activity is high and correlates with ErbB2 and ER-α expression, histological grade, and tumor size.
Predictive factors of outcomes in patients with <scp>AL</scp> amyloidosis treated with daratumumab
Authors: Raphael E. Szalat, Joshua Gustine, J. Mark Sloan, Camille V. Edwards, Vaishali Sanchorawala
Journal: American Journal of Hematology (2021)

Daratumumab as a single agent (sDARA) or in combination with chemotherapies (cDARA) leads to impressive hematologic and organ responses in AL amyloidosis. However, predictive factors associated with outcomes, and optimal duration of therapy remain unclear. We analyzed 107 patients with AL amyloidosis treated with daratumumab between 2017 and 2020. The median overall survival (OS) was not reached while the median major organ deterioration progression free survival (MOD-PFS) was 36 months in the sDARA cohort and not reached in the cDARA cohort, respectively. Hematologic response > VGPR was achieved in 81% of patients receiving sDARA and 86% of patients treated with cDARA. Several predictive factors were identified on a univariate analysis, including NTproBNP >8500 pg/mL but only achievement of at least VGPR and presence of 1q21 gain were independently associated with MOD-PFS and OS on a multivariate analysis. Finally, patients receiving > 12 cycles had significantly longer MOD-PFS (30 vs.13 months; (p = .0018) and OS (NR vs. 15 months; p < .0001). NTproBNP > 8500 pg/mL, presence of 1q21 gain and shorter duration of therapy (≤ 12 cycles) are strong negative predictive factors for outcomes with daratumumab therapy in AL amyloidosis.
TCT-311 Prognostic Impact of Preprocedural Right Ventricular Dysfunction and Tricuspid Regurgitation on Late All-Cause Mortality Following MitraClip Implantation: A Systematic Review and Meta-Analysis
Authors: Israel Safiriyu, Nicole Lao, Olayinka Adebolu, Joseph Lim, Abiodun Idowu, Abdulkareem Lukan, Garba Rimamskep Shamaki, Amit Kakkar
Journal: Journal of the American College of Cardiology (2021)
Impact of HBsAg and HBcrAg levels on phenotype and function of HBV-specific T cells in patients with chronic hepatitis B virus infection
Authors: Elmira Aliabadi, Melanie Urbanek-Quaing, Benjamin Maasoumy, Birgit Bremer, Martin Grasshoff, Yang Li, Christian E Niehaus, Heiner Wedemeyer, Anke R M Kraft, Markus Cornberg
Journal: Gut (2021)

Objective Hepatitis B virus (HBV)-specific T cells are main effector cells in the control of HBV infection and hepatitis B surface antigen (HBsAg) is suggested to be a critical factor in the impaired immune response, a hallmark of chronic HBV infection. In addition to HBsAg, other viral markers such as hepatitis B core-related antigen (HBcrAg) are available, but their potential association with HBV-specific immune responses is not defined yet, which will be important if these markers are used for patient stratification for novel therapies aimed at functional HBV cure. Design We analysed T cell responses in 92 patients with hepatitis B e antigen negative chronic HBV infection with different HBsAg and HBcrAg levels. Overlapping peptides were used for in vitro response analyses (n=57), and HBV core 18 -specific and polymerase (pol) 455 -specific CD8 + T cells were assessed in human leukocyte antigen (HLA)-A*02 patients (n=35). In addition, in vitro responsiveness to anti-programmed cell death-ligand 1 (anti-PD-L1) was investigated. Results HBV-specific T cell responses were not affected by HBsAg levels, but rather by age and CD4 + T cell responses were highest in patients with low HBcrAg levels. The phenotypes and functionality of HBV core 18 -specific and pol 455 -specific CD8 + T cells differed, but HBsAg and HBcrAg levels did not affect their profiles. Blocking with anti-PD-L1 could restore HBV-specific T cells, but the effect was significantly higher in T cells isolated from patients with low HBsAg and in particular low HBcrAg. Conclusion Our data suggest that age and HBcrAg rather than HBsAg, are associated with HBV-specific T cell responses. Finally, very low antigen levels indicated by HBsAg and in particular HBcrAg may influence T cell response to checkpoint inhibition.
New Immunotherapy Combinations Enter the Battlefield of Malignant Mesothelioma
Authors: Mihaela Aldea, Jose Carlos Benitez, Nathalie Chaput, Benjamin Besse
Journal: Cancer Discovery (2021)

Abstract Summary: Chimeric antigen receptor (CAR) T cells targeting mesothelin plus pembrolizumab, and atezolizumab plus bevacizumab, have recently shown clinical efficacy in phase I trials in malignant pleural and peritoneal mesothelioma. Despite being tested in a highly selected patient population and requiring a complex engineering that can hardly be upscaled, CAR T cells combined with pembrolizumab bring the first proof of efficacy in cold solid tumors with low genomic heterogeneity, while atezolizumab–bevacizumab offers an easy-to-use combination of antiangiogenics and immunotherapy in an orphan disease. See related article by Raghav et al., p. 2738. See related article by Adusumilli et al., p. 2748.
TCT-169 Spontaneous Coronary Artery Dissection in Patients With and Without Chronic Systemic Inflammatory Diseases
Authors: Mesfer Alfadhel, Rohit Samuel, Cameron McAlister, Thomas Nestelberger, Andrew Starovoytov, Johandra Argote, Tejana Grewal, Eve Aymong, Jacqueline Saw
Journal: Journal of the American College of Cardiology (2021)
The broadening scope of oral mucositis and oral ulcerative mucosal toxicities of anticancer therapies
Authors: Sharon Elad, Noam Yarom, Yehuda Zadik, Michal Kuten‐Shorrer, Stephen T. Sonis
Journal: CA A Cancer Journal for Clinicians (2021)

CA: A Cancer Journal for Clinicians publishes information about the prevention, early detection, and treatment of cancer, as well as nutrition, palliative care, survivorship, and additional topics of interest related to cancer care.
Beyond Transcription Factors: Remodeling Chromatin in the Metanephric Mesenchyme
Authors: Samir S. El-Dahr
Journal: Journal of the American Society of Nephrology (2021)

During development, cell fate determination is governed not only by the nuclear repertoire of lineage-specific transcription factors (TFs) but also by the access of TFs to their cognate cis-regulatory elements (CREs). Chromatin accessibility is a dynamic process and is constrained by the presence of
Abstract 292: Novel Synthesis of PFC Nanobubble-magnetic Nanoparticles Conjugate for Acute Myocardial Infarction
Authors: Mark C Arokiaraj
Journal: Circulation Research (2017)

Aims: The potential aim of this study was to prepare this conjugate and analyze its basic characteristics. This could help in myocardial salvage or reduction in infarct size which is potentially very useful. Methods and Results: Perfluorocarbon nanobubbles were prepared using standard techniques. PFC nanobubbles-magnetic nanoparticle conjugation was performed and a final solution prepared had a pH of 8.0. The conjugation was performed to form covalent bonding and PBS buffer was used. The final preparation is an emulsion with a PFC content of 25% and 40% concentration in each emulsion of 300 microl. The final volume achieved in the synthesis was 300microl of each concentration, and the final compound was stable. The final sample when evaluated under microscope gives an image shown in figure 1. The polydispersity index was &lt;0.25. The magnetic nanoparticle concentration was 15mg/ml and the particle concentration in 300microl was the particle content was 4.5mg. A drop of emulsion subjected to the magnetic field by a small magnet tends to polarize to one side due to the effect of the magnetic field. These particles are easy and respond quickly to magnetic field. On a glass slide when allowed to dry the conjugate forms a thick film like a mountain, and when a small amount of water is added, and when a small magnet is applied nearby, the particles start moving towards the magnet. The size of the particles is about 100nm by dynamic light scattering. Conclusion: Synthesis of magnetic nanoparticle conjugation with PFC nano bubbles is feasible and stable.
Over 1000 tools reveal trends in the single-cell RNA-seq analysis landscape
Authors: Luke Zappia, Fabian J. Theis
Journal: Genome biology (2021)

Abstract Recent years have seen a revolution in single-cell RNA-sequencing (scRNA-seq) technologies, datasets, and analysis methods. Since 2016, the scRNA-tools database has cataloged software tools for analyzing scRNA-seq data. With the number of tools in the database passing 1000, we provide an update on the state of the project and the field. This data shows the evolution of the field and a change of focus from ordering cells on continuous trajectories to integrating multiple samples and making use of reference datasets. We also find that open science practices reward developers with increased recognition and help accelerate the field.