tbuckley/cabot-search huggingface dataset:
In-vitro biomineralization and biocompatibility of friction stir additively manufactured AZ31B magnesium alloy-hydroxyapatite composites
Authors: Yee-Hsien Ho, Kun Man, Sameehan S. Joshi, Mangesh V. Pantawane, Tso-Chang Wu, Yong Yang, Narendra B. Dahotre
Journal: Bioactive Materials (2020)

The present study aims to evaluate effect of hydroxyapatite (HA, Ca10(PO4)6OH2), a ceramic similar to natural bone, into AZ31B Mg alloy matrix on biomineralization and biocompatibility. The novel friction stir processing additive manufacturing route was employed to fabricate Mg-HA composites. Various HA contents (5, 10, 20 wt%) were incorporated into Mg matrix. Microstructural observation and chemical composition analysis revealed that refined Mg grains and dispersion of HA particles at micro/nanoscales were achieved in Mg-HA composites after the friction stir processing. The biomineralization evaluation were carried out using immersion experiments in simulated body fluid followed by mineral morphology observation and chemical composition analysis. The wettability measurements were conducted to correlate the biomineralization behavior. The results showed improvement in wettability and bone-like Ca/P ratio in apatite deposit on the composites compared to as-received Mg. In addition, the increase of blood compatibility, cell viability and spreading were found in the higher HA content composites, indicating the improved biocompatibility. Therefore, friction stir processed Mg-20 wt%HA composite exhibited the highest wettability and better cell adhesion among other composites due to the effect of increased HA content within Mg matrix.
Molecular analysis of circulating tumor cells of metastatic castration-resistant Prostate Cancer Patients receiving <sup>177</sup>Lu-PSMA-617 Radioligand Therapy
Authors: Katharina Kessel, Robert Seifert, Matthias Weckesser, Wolfgang Roll, Verena Humberg, Katrin Schlack, Martin Bögemann, Christof Bernemann, Kambiz Rahbar
Journal: Theranostics (2020)

Rationale: Lu-177-PSMA-617 radioligand therapy (RLT) is currently under approval for treatment of metastatic castration resistant prostate cancer (mCRPC) patients with late stage disease. However, previous studies demonstrated both heterogeneity of prostate specific membrane antigen (PSMA) expression, as well as response to PSMA treatment among mCRPC patients. Thus, there is an unmet need for identifying predictive parametres prior or under PSMA-RLT treatment. We therefore aimed to correlate several clinical and molecular parameters with response to PSMA treatment in a cohort of mCRPC patients undergoing PSMA RLT followed by a detailed analysis of promising candidates. Methods: Nineteen patients, median age 68.8 years (range: 56.9 - 83.3) with mCRPC were included in this study. We performed baseline analysis of clinical parameters based on PSMA PET/CT, (metabolic tumor volume (MTV), total tumor volume (TTV)), serum PSA, ALP, LDH and gene expression analysis of circulating tumor cells (expression of AR full length (AR-FL), AR splice variant 7 (AR-V7), PSA and PSMA) as well as common markers for neuroendocrine differentiation (NED). Results: Patients presented with bone, lymph node, and visceral metastases (89%, 68%, and 21%, respectively). All patients were pretreated with docetaxel, either abiraterone or enzalutamide, or both. Biochemical response in terms of PSA decline ≥50 or ≥30% was observed in 42% and 63%, respectively. There were significant correlations between PSA and PSMA mRNA expression, as well as tumor volumes (both MTV and TTV), AR-FL and AR-V7 mRNA expression. However, there was no correlation with response to PSMA treatment. Furthermore, none of these parameters was significantly correlated with baseline serum PSA values. Common NED markers were shown to be specifically high expressed and revealed impact on OS independent from AR-V7 gene expression. Conclusion: We demonstrate that AR-FL and its splice variant AR-V7 might serve as prognostic biomarkers displaying high tumor burden in mCRPC patient prior to PSMA-RLT. Contrary, PSMA, which has been discussed as a biomarker for PSMA targeted treatment, does not display strong prognostic ability - at least on the mRNA level. Surprisingly, none of these parameters correlates to response to PSMA treatment. In contrast, commom NED markers such as SYP and ENO2 as well as FOXA1 expression level seem to predict OS, but not PFS, more reliably. We admit that a limitation of our study is the focus on mRNA expression of potential biomarkers only. Further investigations analyzing the potential role of protein expression of these markers are therefore warranted.
Abstract 250: Characterization of Events Surrounding Re-Arrest After Return of Spontaneous Circulation During Prehospital Treatment of Cardiac Arrest
Authors: Don Lundy, W T McGeorge, Gary Freeman, Annemarie Silver
Journal: Circulation (2010)

Introduction: It has been recently reported that over a third of out-of-hospital cardiac arrest patients with return of spontaneous circulation (ROSC) re-arrest in the pre-hospital environment afte...
MRI Distinguishes Tumor Hypoxia Levels of Different Prognostic and Biological Significance in Cervical Cancer
Authors: Tiril Hillestad, Tord Hompland, Christina S. Fjeldbo, Vilde E. Skingen, Unn Beate Salberg, Eva-Katrine Aarnes, Anja Nilsen, Kjersti V. Lund, Tina S. Evensen, Gunnar B. Kristensen, Trond Stokke, Heidi Lyng
Journal: Cancer Research (2020)

Abstract Tumor hypoxia levels range from mild to severe and have different biological and therapeutical consequences but are not easily assessable in patients. Here we present a method based on diagnostic dynamic contrast enhanced (DCE) MRI that reflects a continuous range of hypoxia levels in patients with tumors of cervical cancer. Hypoxia images were generated using an established approach based on pixel-wise combination of DCE-MRI parameters νe and Ktrans, representing oxygen consumption and supply, respectively. Using two tumor models, an algorithm to retrieve surrogate measures of hypoxia levels from the images was developed and validated by comparing the MRI-defined levels with hypoxia levels reflected in pimonidazole-stained histologic sections. An additional indicator of hypoxia levels in patient tumors was established on the basis of expression of nine hypoxia-responsive genes; a strong correlation was found between these indicator values and MRI-defined hypoxia levels in 63 patients. Chemoradiotherapy outcome of 74 patients was most strongly predicted by moderate hypoxia levels, whereas more severe or milder levels were less predictive. By combining gene expression profiles and MRI-defined hypoxia levels in cancer hallmark analysis, we identified a distribution of levels associated with each hallmark; oxidative phosphorylation and G2–M checkpoint were associated with moderate hypoxia, epithelial-to-mesenchymal transition, and inflammatory responses with significantly more severe levels. At the mildest levels, IFN response hallmarks together with HIF1A protein expression by IHC appeared significant. Thus, our method visualizes the distribution of hypoxia levels within patient tumors and has potential to distinguish levels of different prognostic and biological significance. Significance: These findings present an approach to image a continuous range of hypoxia levels in tumors and demonstrate the combination of imaging with molecular data to better understand the biology behind these different levels.
Pulmonary arterial hypertension associated with primary Sjögren's syndrome: a multicentre cohort study from China
Authors: Jieying Wang, Mengtao Li, Qian Wang, Xiao Zhang, Junyan Qian, Jiuliang Zhao, Dong Xu, Zhuang Tian, Wei Wei, Xiaoxia Zuo, Miaojia Zhang, Ping Zhu, Shuang Ye, Wei Zhang, Yi Zheng, Wufang Qi, Yang Li, Zhuoli Zhang, Feng Ding, Jieruo Gu, Yi Liu, Yanhong Wang, Yan Zhao, Xiaofeng Zeng
Journal: European Respiratory Journal (2020)

Objectives Primary Sjögren's syndrome (pSS) is an important cause of pulmonary arterial hypertension (PAH), which remains insufficiently studied and needs attention. This study aimed to investigate the clinical characteristics, risk factors, prognosis and risk assessment of pSS-PAH. Methods We established a multicentre cohort of pSS-PAH diagnosed by right heart catheterisation. The case–control study was conducted with pSS-non-PAH patients as a control group to identify the risk factors for PAH. In the cohort study, survival was calculated, and risk assessment was performed at both baseline and follow-up visits. Results In total, 103 patients with pSS-PAH were enrolled, with 526 pSS-non-PAH patients as controls. The presence of anti-SSB (p&lt;0.001, OR 4.095) and anti-U1RNP antibodies (p&lt;0.001, OR 29.518), the age of pSS onset (p&lt;0.001, OR 0.651) and the positivity of corneal staining (p=0.003, OR 0.409) were identified as independent risk factors for PAH. The 1-, 3- and 5-year survival rates were 94.0%, 88.8% and 79.0%, respectively. Cardiac index (p=0.010, hazard ratio (HR) 0.161), pulmonary vascular resistance (p=0.016, HR 1.105) and Sjögren's syndrome disease damage index (p=0.006, HR 1.570) were identified as potential predictors of death in pSS-PAH. Long-term outcomes were improved in patients in the low-risk category at baseline (p=0.002) and follow-up (p&lt;0.0001). Conclusion The routine screening of PAH is suggested in pSS patients with early onset and positivity for anti-SSB or anti-U1RNP antibodies. Patient prognosis might be improved by improving reserved cardiopulmonary function, by achieving a damage-free state and especially by achieving low-risk category, which supports the treat-to-target strategy for pSS-PAH.
10-Year Outcomes From a Randomized Trial of Polymer-Free Versus Durable Polymer Drug-Eluting Coronary Stents
Authors: Sebastian Kufner, Maximilian Ernst, Salvatore Cassese, Michael Joner, Katharina Mayer, Roisin Colleran, Tobias Koppara, Erion Xhepa, Tobias Koch, Jens Wiebe, Tareq Ibrahim, Massimiliano Fusaro, Karl-Ludwig Laugwitz, Heribert Schunkert, Adnan Kastrati, Robert A. Byrne
Journal: Journal of the American College of Cardiology (2020)

Outcome data after extended long-term follow-up of patients with coronary artery disease treated with drug-eluting stents (DES) in randomized clinical trials are scant. Performance differences among devices may be expected to emerge over time depending on whether stenting is done with polymer-free or durable polymer DES. This study assessed the 10-year outcomes of patients enrolled in the ISAR-TEST-5 (Test Efficacy of Sirolimus- and Probucol-Eluting Versus Zotarolimus-Eluting Stents) trial. A total of 3,002 patients were randomized to treatment with either polymer-free sirolimus- and probucol-eluting stents (n = 2,002) or durable polymer zotarolimus-eluting stents (n = 1,000). The primary endpoint was the composite of cardiac death, target vessel–related myocardial infarction, or target lesion revascularization (a device-oriented composite endpoint [DOCE]). Additional endpoints of interest were the patient-oriented composite endpoint (POCE), including all-cause death, any myocardial infarction, or any revascularization; individual components of the composite endpoints; and definite or probable stent thrombosis. The median age of the patients at randomization was 67.8 years. At 10 years, 63.9% of patients were alive. The rates of DOCE and POCE were high in both groups with no difference in the incidence between polymer-free sirolimus- and probucol-eluting stents and durable polymer zotarolimus-eluting stents (DOCE: 43.8% vs. 43.0%, respectively; hazard ratio: 1.01; 95% confidence interval [CI]: 0.89 to 1.14; p = 0.90; POCE: 66.2% vs. 67.7%, respectively; hazard ratio: 0.94; 95% CI: 0.86 to 1.04; p = 0.22). The rates of the individual components of the composite endpoints were comparable in both groups. The incidence of definite/probable stent thrombosis over 10 years was low and comparable in both groups (1.6% vs. 1.9%; hazard ratio: 0.85; 95% CI: 0.46 to 1.54; p = 0.58). At 10 years, there were no measurable differences in outcomes between patients treated with polymer-free versus durable polymer DES. The incidence of stent thrombosis was low and comparable in both groups. High overall adverse clinical event rates were observed during extended follow-up. (Test Efficacy of Sirolimus- and Probucol-Eluting Versus Zotarolimus-Eluting Stents [ISAR-TEST-5]; NCT00598533)
Novel agents targeting leukemia cells and immune microenvironment for prevention and treatment of relapse of acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation
Authors: Wei Shi, Weiwei Jin, Linghui Xia, Yu Hu
Journal: Acta Pharmaceutica Sinica B (2020)

Relapse remains the worst life-threatening complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with acute myeloid leukemia (AML), whose prognosis has been historically dismal. Given the rapid development of genomics and immunotherapies, the interference strategies for AML recurrence have been changing these years. More and more novel targeting agents that have received the U.S. Food and Drug Administration (FDA) approval for de novo AML treatment have been administrated in the salvage or maintenance therapy of post-HSCT relapse. Targeted strategies that regulate the immune microenvironment of and optimize the graft versus leukemia (GVL) effect of immune cells are gradually improved. Such agents not only have been proven to achieve clinical benefits from a single drug, but if combined with classic therapies, can significantly improve the poor prognosis of AML patients who relapse after allo-HSCT. This review will focus on currently available and promising upcoming agents and also discuss the challenges and limitations of targeted therapies in the allogeneic hematopoietic stem cell transplantation community.
THU0017 The Role of HLA DQ2 and DQ8 in Dissecting Celiac-Like Disease in Common Variable Immunodeficiency
Authors: J. Thiel, F. Emmerich, M. Neagu, U. Salzer, R. E. Voll, C. Koehn, N. Venhoff
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Gastrointestinal manifestations are frequent in patients with common variable immunodeficiency (CVID), and present with celiac-like features in a subgroup of these patients. On the other hand diagnosing bona fide/authentic celiac disease (CD) in CVID is challenging, as serology and small intestine histopathology cannot reliably discriminate between true CD and a celiac-like disease phenotype in these individuals. In CD a special HLA haplotype involving the loci <i>DQA1*</i> and <i>DQB1*</i> and encoding two different HLA DQ heterodimers is the prerequisite for disease development. <h3>Objectives</h3> We aim to determine the frequency of these haplotypes in CVID patients with suspected CD. Furthermore, we report on autoimmune manifestations and the lymphocyte phenotype in these patients. <h3>Methods</h3> By retrospective analysis data on gastrointestinal symptoms, concurrent autoimmune diseases, and routine laboratory values were collected. CVID patients were classified by phenotyping of their peripheral B-lymphocytes. <i>HLA-DQA1*</i> and <i>HLA-DQB1*</i> genes were analyzed to determine the frequency of CD associated heterodimers. <h3>Results</h3> 20 out of 250 CVID patients presented with a clinical phenotype resembling celiac disease. 5 (25%) out of these CVID patients carried the CD-associated HLA DQ2.5 or DQ8 heterodimer, while HLA DQ2.5 was present in 100% of a CD control cohort. Gluten-free diet (GFD) resulted in a clinical and histological response in 2 out of 5 patients with HLA high-risk alleles for CD. The response could not be assessed in the remaining 3 patients, as these patients did not adhere sufficiently long to GFD. The percentage of autoimmune manifestations other then CD was high (50%) in CVID patients presenting with a CD-like enteropathy, and most of these patients had an expansion of B-cells with low expression of CD21 (CD21low B-cells). <h3>Conclusions</h3> In CVID patients with suspected celiac disease typing of the HLA loci <i>DQA1</i> and <i>DQB1</i> can help to identify those that have a genetic susceptibility for CD. In CVID patients with a celiac-like phenotype but negativity for the HLA-DQ markers predisposing to CD, an alternative pathogenesis of gastrointestinal manifestations should be favoured. This has important implications for further diagnostics and therapy of these patients. <h3>Disclosure of Interest</h3> None Declared
Altered Properties of Endothelial Cells and Mesenchymal Stem Cells Underlying the Development of Scleroderma‐like Vasculopathy in KLF5<sup>+/−</sup>;Fli‐1<sup>+/−</sup> Mice
Authors: Kouki Nakamura, Takashi Taniguchi, Megumi Hirabayashi, Takashi Yamashita, Ryosuke Saigusa, Shunsuke Miura, Takehiro Takahashi, Tetsuo Toyama, Yohei Ichimura, Ayumi Yoshizaki, Maria Trojanowska, Katsuhito Fujiu, Ryozo Nagai, Shinichi Sato, Yoshihide Asano
Journal: Arthritis & Rheumatology (2020)

Objective In prevous studies, we established a new animal model, KLF5 +/− ;Fli‐1 +/− mice, in which fundamental pathologic features of systemic sclerosis (SSc) are broadly recapitulated. SSc vasculopathy is believed to occur as a result of impaired vascular remodeling, but its detailed mechanism of action remains unknown. To address this, the present study investigated the properties of dermal microvascular endothelial cells (DMECs), bone marrow–derived endothelial progenitor cells (BM‐EPCs), and bone marrow–derived mesenchymal stem cells (BM‐MSCs), a precursor of pericytes, in KLF5 +/− ;Fli‐1 +/− mice. Methods Neovascularization and angiogenesis were assessed in KLF5 +/− ;Fli‐1 +/− mice by in vivo Matrigel plug assay and in vitro tube formation assay, respectively. The properties of mouse BM‐EPCs and BM‐MSCs were assessed with in vitro studies. Dermal vasculature was visualized in vivo by injecting the mice with fluorescein isothiocyanate–conjugated dextran. Results Neovascularization was diminished in skin‐embedded Matrigel plugs from KLF5 +/− ;Fli‐1 +/− mice. DMECs from KLF5 +/− ;Fli‐1 +/− mice showed defective tubulogenic activity, decreased expression of VE‐cadherin and CD31, and an imbalance in the expression of Notch 1 / Dll4 , suggesting that angiogenesis and anastomosis are disturbed. KLF5 +/− ;Fli‐1 +/− mouse BM‐MSCs exhibited enhanced proliferation and migration and increased collagen production following stimulation with transforming growth factor β1, indicating that these cells differentiate preferentially into myofibroblasts rather than pericytes. KLF5 +/− ;Fli‐1 +/− mouse BM‐EPCs displayed a transition toward mesenchymal cells, suggesting that vasculogenesis is impaired. Wound healing was delayed in KLF5 +/− ;Fli‐1 +/− mice (mean ± SD healing time 15.67 ± 0.82 days versus 13.50 ± 0.84 days; P = 0.0017), and the vascular network was poorly developed in wound scar tissue. Conclusion The characteristics observed in the KLF5 +/− ;Fli‐1 +/− mouse model — specifically, impaired neovascularization and vascular maturation — are similar to those observed in human SSc, and could be at least partially attributable to the induction of SSc‐like properties in DMECs, BM‐EPCs, and BM‐MSCs. These findings indicate the critical contribution of Klf5 and Fli1 deficiency in vascular cells and related cell precursors to the development of SSc vasculopathy.
Direct Oral Anticoagulants in Patients With Active Cancer
Authors: Jolanda Sabatino, Salvatore De Rosa, Alberto Polimeni, Sabato Sorrentino, Ciro Indolfi
Journal: JACC CardioOncology (2020)

Many patients with cancer have a hypercoagulable state and an increased risk of developing venous thromboembolism (VTE), arterial occlusion, and pulmonary emboli. Patients with cancer may also have an increased risk of bleeding with anticoagulant treatment. Recent trials have reported that direct oral anticoagulants (DOACs) are noninferior to the low-molecular-weight heparin, dalteparin, in preventing VTE, but have a higher bleeding rate.This study compared the efficacy and risks of DOACs versus dalteparin in patients with cancer-related VTEs across all randomized controlled trials (RCTs).This study performed a systematic analysis of RCTs published in PubMed, SCOPUS, and Google Scholar from September 1, 2007 through March 31, 2020 that reported clinical outcomes of treatment with DOACs versus dalteparin in patients with cancer with acute VTE. Two investigators independently performed study selection and data extraction. Extracted data were recorded and exported to statistical software for all analyses (OpenMetaAnalyst).This study included 4 randomized trials (N = 2,907). Compared with DOACs, dalteparin was associated with higher VTE recurrence (risk ratio [RR]: 1.55; 95% confidence interval [CI]: 1.19 to 2.03; p = 0.001), whereas clinically relevant nonmajor bleeding (CRNMB) was significantly less frequent with dalteparin than that with DOACs (RR: 0.68; 95% CI: 0.54 to 0.86; p = 0.001). The risk of CRNMB was largely observed with patients with gastrointestinal malignancies. No significant differences were observed in major bleeding (RR: 0.74; 95% CI: 0.52 to 1.06; p = 0.11).DOACs were noninferior to dalteparin in preventing VTE recurrence in patients with cancer without a significantly increased risk of major bleeding. However, DOACs were associated with higher rates of CRNMB compared with dalteparin, primarily in patients with gastrointestinal malignancies.
Personalized surveillance for hepatocellular carcinoma in cirrhosis – using machine learning adapted to HCV status
Authors: Etienne Audureau, Fabrice Carrat, Richard Layese, Carole Cagnot, Tarik Asselah, Dominique Guyader, Dominique Larrey, Victor De Lédinghen, Denis Ouzan, Fabien Zoulim, Dominique Roulot, Albert Tran, Jean-Pierre Bronowicki, Jean-Pierre Zarski, Ghassan Riachi, Paul Calès, Jean-Marie Péron, Laurent Alric, Marc Bourlière, Philippe Mathurin, Jean-Frédéric Blanc, Armand Abergel, Olivier Chazouillères, Ariane Mallat, Jean-Didier Grangé, Pierre Attali, Louis d'Alteroche, Claire Wartelle, Thông Dao, Dominique Thabut, Christophe Pilette, Christine Silvain, Christos Christidis, Eric Nguyen-Khac, Brigitte Bernard-Chabert, David Zucman, Vincent Di Martino, Angela Sutton, Stanislas Pol, Pierre Nahon
Journal: Journal of Hepatology (2020)
Osteoblast/fibroblast coculture derived bioactive ECM with unique matrisome profile facilitates bone regeneration
Authors: Mei Li, Anqi Zhang, Jiajing Li, Jing Zhou, Yanan Zheng, Chi Zhang, Dongdong Xia, Haijiao Mao, Jiyuan Zhao
Journal: Bioactive Materials (2020)

Extracellular matrix (ECM) with mimetic tissue niches was attractive to facilitate tissue regeneration in situ via recruitment of endogenous cells and stimulation of self-healing process. However, how to engineer the complicate tissue specific ECM with unique matrisome in vitro was a challenge of ECM-based biomaterials in tissue engineering and regenerative medicine. Here, we introduced coculture system to engineer bone mimetic ECM niche guided by cell-cell communication. In the cocultures, fibroblasts promoted osteogenic differentiation of osteoblasts via extracellular vesicles. The generated ECM (MN-ECM) displayed a unique appearance of morphology and biological components. The advantages of MN-ECM were demonstrated with promotion of multiple cellular behaviors (proliferation, adhesion and osteogenic mineralization) in vitro and bone regeneration in vivo. Moreover, proteomic analysis was used to clarify the molecular mechanism of MN-ECM, which revealed a specific matrisome signature. The present study provides a novel strategy to generate ECM with tissue mimetic niches via cell-cell communication in a coculture system, which forwards the development of tissue-bioactive ECM engineering along with deepening the understanding of ECM niches regulated by cells for bone tissue engineering.