bluuebunny/crossref_metadata_2025_split huggingface dataset:
Singularity Intensity Function Analysis of Autoregressive Spectrum and Its Application in Weak Target Detection Under Sea Clutter Background
Authors: Jiang Zheng‐jie , Fan Yi‐fei 
Published: July 2020

AbstractWeak target detection based on fractal analysis under rada sea clutter background is an open problem. The existing methods, using single fractal dimension and Hurst exponent in time domain or Fourier domain, are not applicable under low signal‐to‐clutter ratio (SCR) conditions. Since autoregressive (AR) spectrum has the advantage of high‐frequency resolution over the Fourier spectrum in sea clutter analysis, while multifracal theory is an extension of single fractal analysis. Therefore, we combined the multifractal analysis with AR spectrum estimate theory. Since singularity intensity function is an important parameter to describe a multifractal set, this paper proposed a weak target detection method based on singularity intensity function of AR spectrum under the sea clutter background. Then real S‐band data sets are used to analyze the singularity intensity function of AR spectrum, and the results show that the AR singularity intensity function between sea clutter and targets has different value range interval. Finally, the singularity intensity function width of AR spectrum is taken as a statistical test for weak target detection. Compared to the existing fractal methods method, the proposed target detection method improves the detection probability over 20% in low SCR condition.
Investigation of the safety and feasibility of AAV1/SERCA2a gene transfer in patients with chronic heart failure supported with a left ventricular assist device – the SERCA-LVAD TRIAL
Authors: Lyon A. R. , Babalis D. , Morley-Smith A. C. , Hedger M. , Suarez Barrientos A. , Foldes G. , Couch L. S. , Chowdhury R. A. , Tzortzis K. N. , Peters N. S. , Rog-Zielinska E. A. , Yang H-Y , Welch S. , Bowles C. T. , Rahman Haley S. , Bell A. R. , Rice A. , Sasikaran T. , Johnson N. A. , Falaschetti E. , Parameshwar J. , Lewis C. , Tsui S. , Simon A. , Pepper J. , Rudy J. J. , Zsebo K. M. , Macleod K. T. , Terracciano C. M. , Hajjar R. J. , Banner N. , Harding S. E. 
Published: July 2020

AbstractThe SERCA-LVAD trial was a phase 2a trial assessing the safety and feasibility of delivering an adeno-associated vector 1 carrying the cardiac isoform of the sarcoplasmic reticulum calcium ATPase (AAV1/SERCA2a) to adult chronic heart failure patients implanted with a left ventricular assist device. The SERCA-LVAD trial was one of a program of AAV1/SERCA2a cardiac gene therapy trials including CUPID1, CUPID 2 and AGENT trials. Enroled subjects were randomised to receive a single intracoronary infusion of 1 × 1013 DNase-resistant AAV1/SERCA2a particles or a placebo solution in a double-blinded design, stratified by presence of neutralising antibodies to AAV. Elective endomyocardial biopsy was performed at 6 months unless the subject had undergone cardiac transplantation, with myocardial samples assessed for the presence of exogenous viral DNA from the treatment vector. Safety assessments including ELISPOT were serially performed. Although designed as a 24 subject trial, recruitment was stopped after five subjects had been randomised and received infusion due to the neutral result from the CUPID 2 trial. Here we describe the results from the 5 patients at 3 years follow up, which confirmed that viral DNA was delivered to the failing human heart in 2 patients receiving gene therapy with vector detectable at follow up endomyocardial biopsy or cardiac transplantation. Absolute levels of detectable transgene DNA were low, and no functional benefit was observed. There were no safety concerns in this small cohort. This trial identified some of the challenges of performing gene therapy trials in this LVAD patient cohort which may help guide future trial design.
Blood genome expression profiles in infants with congenital cytomegalovirus infection
Authors: Ouellette Christopher P. , Sánchez Pablo J. , Xu Zhaohui , Blankenship Derek , Zeray Fiker , Ronchi Andrea , Shimamura Masako , Chaussabel Damien , Lee Lizette , Owen Kris E. , Shoup Angela G. , Ramilo Octavio , Mejias Asuncion 
Published: July 2020

AbstractCongenital CMV infection (cCMVi) affects 0.5–1% of all live births worldwide, making it the leading cause of sensorineural hearing loss (SNHL) in childhood. The majority of infants with cCMVi have normal hearing at birth, but are at risk of developing late-onset SNHL. Currently, we lack reliable biomarkers to predict the development of SNHL in these infants. Here, we evaluate blood transcriptional profiles in 80 infants with cCMVi (49 symptomatic, 31 asymptomatic), enrolled in the first 3 weeks of life, and followed for 3 years to assess emergence of late-onset SNHL. The biosignatures of symptomatic and asymptomatic cCMVi are indistinguishable, suggesting that immune responses of infants with asymptomatic and symptomatic cCMVi are not different. Random forest analyses of initial samples in infants with cCMVi, irrespective of their clinical classification, identify a 16-gene classifier signature associated with the development of SNHL with 92% accuracy, suggesting its potential value as a biomarker.
Structural snapshots of human pre-60S ribosomal particles before and after nuclear export
Authors: Liang Xiaomeng , Zuo Mei-Qing , Zhang Yunyang , Li Ningning , Ma Chengying , Dong Meng-Qiu , Gao Ning 
Published: July 2020

AbstractRibosome biogenesis is an elaborate and energetically expensive program that involve two hundred protein factors in eukaryotes. Nuclear export of pre-ribosomal particles is one central step which also serves as an internal structural checkpoint to ensure the proper completion of nuclear assembly events. Here we present four structures of human pre-60S particles isolated through a nuclear export factor NMD3, representing assembly stages immediately before and after nuclear export. These structures reveal locations of a dozen of human factors, including an uncharacterized factor TMA16 localized between the 5S RNA and the P0 stalk. Comparison of these structures shows a progressive maturation for the functional regions, such as peptidyl transferase centre and peptide exit tunnel, and illustrate a sequence of factor-assisted rRNA maturation events. These data facilitate our understanding of the global conservation of ribosome assembly in eukaryotes and species-specific features of human assembly factors.
Rieske iron-sulfur protein induces FKBP12.6/RyR2 complex remodeling and subsequent pulmonary hypertension through NF-κB/cyclin D1 pathway
Authors: Mei Lin , Zheng Yun-Min , Song Tengyao , Yadav Vishal R. , Joseph Leroy C. , Truong Lillian , Kandhi Sharath , Barroso Margarida M. , Takeshima Hiroshi , Judson Marc A. , Wang Yong-Xiao 
Published: July 2020

AbstractCa2+ signaling in pulmonary arterial smooth muscle cells (PASMCs) plays an important role in pulmonary hypertension (PH). However, the underlying specific ion channel mechanisms remain largely unknown. Here, we report ryanodine receptor (RyR) channel activity and Ca2+ release both are increased, and association of RyR2 by FK506 binding protein 12.6 (FKBP12.6) is decreased in PASMCs from mice with chronic hypoxia (CH)-induced PH. Smooth muscle cell (SMC)-specific RyR2 knockout (KO) or Rieske iron-sulfur protein (RISP) knockdown inhibits the altered Ca2+ signaling, increased nuclear factor (NF)-κB/cyclin D1 activation and cell proliferation, and CH-induced PH in mice. FKBP12.6 KO or FK506 treatment enhances CH-induced PH, while S107 (a specific stabilizer of RyR2/FKBP12.6 complex) produces an opposite effect. In conclusion, CH causes RISP-dependent ROS generation and FKBP12.6/RyR2 dissociation, leading to PH. RISP inhibition, RyR2/FKBP12.6 complex stabilization and Ca2+ release blockade may be potentially beneficial for the treatment of PH.
Ion sieving by a two-dimensional Ti3C2Tx alginate lamellar membrane with stable interlayer spacing
Authors: Wang Jin , Zhang Zhijie , Zhu Jiani , Tian Mengtao , Zheng Shuchang , Wang Fudi , Wang Xudong , Wang Lei 
Published: July 2020

AbstractTwo-dimensional membranes attract extensive interest due to the anomalous transport phenomena; however, the ion separation performance is below the theoretical prediction. The stabilization of d-spacing is a key step for enhancing ion selectivity. Here, we demonstrate a strategy for stabilizing the Ti3C2Tx laminar architecture by alginate hydrogel pillars. After pillared by Ca-alginate, the nanochannel diameters are effectively fixed at 7.4 ± 0.2 Å, and the membrane presents a permeation cutoff and an outstanding sieving property towards valent cations. When applied for acid recovery, the outstanding H+/Fe2+ selectivity makes the membrane a promising substitution for traditional ion-exchange membranes. Moreover, the ultrathin Mn-alginate pillared membrane with identical d-spacing exhibits 100% Na2SO4 rejection with high water permeance, which is superior to the state-of-the-art nanofiltration membranes. Building on these findings, we demonstrate an efficient method to tune the ion selectivity and introduce a new perspective for energy- and environment-related applications.
The TLR9 ligand CpG ODN 2006 is a poor adjuvant for the induction of de novo CD8+ T-cell responses in vitro
Authors: Papagno Laura , Kuse Nozomi , Lissina Anna , Gostick Emma , Price David A. , Appay Victor , Nicoli Francesco 
Published: July 2020

AbstractToll-like receptor 9 (TLR9) agonists have gained traction in recent years as potential adjuvants for the induction of adaptive immune responses. It has nonetheless remained unclear to what extent such ligands can facilitate the priming events that generate antigen-specific effector and/or memory CD8+ T-cell populations. We used an established in vitro model to prime naive precursors from human peripheral blood mononuclear cells in the presence of various adjuvants, including CpG ODN 2006, a synthetic oligonucleotide TLR9 ligand (TLR9L). Unexpectedly, we found that TLR9L induced a suboptimal inflammatory milieu and promoted the antigen-driven expansion and functional maturation of naive CD8+ T cells ineffectively compared with either ssRNA40 or 2′3′-cGAMP, which activate other pattern recognition receptors (PRRs). TLR9L also inhibited the priming efficacy of 2′3′-cGAMP. Collectively, these results suggest that TLR9L is unlikely to be a good candidate for the optimal induction of de novo CD8+ T-cell responses, in contrast to adjuvants that operate via discrete PRRs.
RETRACTED ARTICLE: Suppressor capacity of copper nanoparticles biosynthesized using Crocus sativus L. leaf aqueous extract on methadone-induced cell death in adrenal phaeochromocytoma (PC12) cell line
Authors: Zhang Peng , Cui Jian , Mansooridara Shirin , Kalantari Atoosa Shahriyari , Zangeneh Akram , Zangeneh Mohammad Mahdi , Sadeghian Nastaran , Taslimi Parham , Bayat Ramazan , Şen Fatih 
Published: July 2020

AbstractIn this research, we prepared and formulated a neuroprotective supplement (copper nanoparticles in aqueous medium utilizingCrocus sativusL. Leaf aqueous extract) for determining its potential against methadone-induced cell death in PC12. The results of chemical characterization tests i.e., FE-SEM, FT-IR, XRD, EDX, TEM, and UV–Vis spectroscopy revealed that the study showed that copper nanoparticles were synthesized in the perfect way possible. In the TEM and FE-SEM images, the copper nanoparticles were in the mean size of 27.5 nm with the spherical shape. In the biological part of the present research, the Rat inflammatory cytokine assay kit was used to measure the concentrations of inflammatory cytokines. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) test was used to show DNA fragmentation and apoptosis. Caspase-3 activity was assessed by the caspase activity colorimetric assay kit and mitochondrial membrane potential was studied by Rhodamine123 fluorescence dye. Also, the cell viability of PC12 was measured by trypan blue assay. Copper nanoparticles-treated cell cutlers significantly (p ≤ 0.01) decreased the inflammatory cytokines concentrations, caspase-3 activity, and DNA fragmentation and they raised the cell viability and mitochondrial membrane potential in the high concentration of methadone-treated PC12 cells. The best result of neuroprotective properties was seen in the high dose of copper nanoparticles i.e., 4 µg. According to the above results, copper nanoparticles containingC. sativusleaf aqueous extract can be used in peripheral nervous system treatment as a neuroprotective promoter and central nervous system after approving in the clinical trial studies in humans.
The application of deep learning based diagnostic system to cervical squamous intraepithelial lesions recognition in colposcopy images
Authors: Yuan Chunnv , Yao Yeli , Cheng Bei , Cheng Yifan , Li Ying , Li Yang , Liu Xuechen , Cheng Xiaodong , Xie Xing , Wu Jian , Wang Xinyu , Lu Weiguo 
Published: July 2020

AbstractBackground Deep learning has presented considerable potential and is gaining more importance in computer assisted diagnosis. As the gold standard for pathologically diagnosing cervical intraepithelial lesions and invasive cervical cancer, colposcopy-guided biopsy faces challenges in improving accuracy and efficiency worldwide, especially in developing countries. To ease the heavy burden of cervical cancer screening, it is urgent to establish a scientific, accurate and efficient method for assisting diagnosis and biopsy. Methods The data were collected to establish three deep-learning-based models. For every case, one saline image, one acetic image, one iodine image and the corresponding clinical information, including age, the results of human papillomavirus testing and cytology, type of transformation zone, and pathologic diagnosis, were collected. The dataset was proportionally divided into three subsets including the training set, the test set and the validation set, at a ratio of 8:1:1. The validation set was used to evaluate model performance. After model establishment, an independent dataset of high-definition images was collected to further evaluate the model performance. In addition, the comparison of diagnostic accuracy between colposcopists and models weas performed. Results The sensitivity, specificity and accuracy of the classification model to differentiate negative cases from positive cases were 85.38%, 82.62% and 84.10% respectively, with an AUC of 0.93. The recall and DICE of the segmentation model to segment suspicious lesions in acetic images were 84.73% and 61.64%, with an average accuracy of 95.59%. Furthermore, 84.67% of high-grade lesions were detected by the acetic detection model. Compared to colposcopists, the diagnostic system performed better in ordinary colposcopy images but slightly unsatisfactory in high-definition images. Implications The deep learning-based diagnostic system could help assist colposcopy diagnosis and biopsy for HSILs.
Pharmacokinetics and safety of IBI301 versus rituximab in patients with CD20+ B-cell lymphoma: a multicenter, randomized, double-blind, parallel-controlled study
Authors: Jiang Bo , Ke Xiaoyan , Zhang Qingyuan , Xu Wei , Su Hang , Huang Jie , Zhang Mingzhi , Wang Huaqing , Jin Chuan , Zhu Jun , Liu Li , Cai Zhen , Zhao Xielan , Zhou Jianfeng , Zhang Xiaohong , Liu Jing , Zhou Hui , Yu Jie , Sun Xing , Qi Junyuan , Qiu Lugui 
Published: July 2020

AbstractThis multicenter, randomized, double-blind, parallel-controlled trial aimed to compare the pharmacokinetics (PK) of IBI301 with rituximab in patients with CD20-positive (CD20+) B-cell lymphoma, who achieved a complete response/unconfirmed complete response after standard treatments. Patients were randomized (1:1) to receive IBI301 or rituximab (375 mg/m2, IV). Patients who continuously benefitted from the trial after the PK phase underwent the extension phase to receive up to three cycles of 3-month-cycle of rituximab/IBI301 maintenance therapy. PK was described using the area under the serum concentration–time curve from time zero to infinity (AUC0-inf), AUC from time zero to last quantifiable concentration (AUC0-t), and maximum serum concentration (Cmax). Pharmacodynamics (PD), incidence of adverse events and immunogenicity were evaluated. PK was defined equivalent, if 90% confidence intervals (CIs) for geometric mean ratios of PK endpoints fell within the margin of 0.8–1.25. Overall, 181 patients were enrolled in IBI301 (n = 89) and rituximab (n = 92) groups. Geometric mean ratios of AUC0-inf, AUC0-t, and Cmax were 0.91 (90% CI 0.85, 0.97), 0.91 (90% CI 0.86, 0.97), and 0.96 (90% CI 0.92, 1.01) between treatment groups, all within the bioequivalence range. Peripheral CD19+ and CD20+ B-cell counts were similar at each prespecified time point between the groups. No difference in immunogenicity was observed. The incidences of treatment-emergent adverse events (84.3% vs. 83.5%) and treatment-related AEs (56.2% vs. 61.5%) were comparable (IBI301 vs. rituximab). IBI301 was PK bioequivalent to rituximab in patients with CD20+ B-cell lymphoma. The PD, safety, and immunogenicity profiles of IBI301 were similar to those of rituximab.
Development of novel and green NiFe2O4/geopolymer nanocatalyst based on bentonite for synthesis of imidazole heterocycles by ultrasonic irradiations
Authors: Hajizadeh Zoleikha , Radinekiyan Fateme , Eivazzadeh-keihan Reza , Maleki Ali 
Published: July 2020

AbstractGeopolymers as aluminosilicate inorganic polymers and eco-friendly building materials which can be used as substrate for different kinds of composite. In this research, according to the fabrication of geopolymer based on bentonite as a substrate and embedment of NiFe2O4 nanoparticles in the construction of this polymer, the synthesis of a new magnetic nanocomposite (NiFe2O4/geopolymer) was investigated for the first time. In order to describe its chemistry and morphology features, different analyses such as Fourier transform infrared spectroscopy, field-emission scanning electron microscopy and transmission electron microscopy images, Brunauer–Emmet–Teller adsorption–desorption isotherm, X-ray diffraction pattern, energy-dispersive X-ray analysis, thermogravimetric analysis, and vibrating-sample magnetometer analysis were used. The application of this novel nanocatalyst was studied for one-pot three-component condensation reaction of substituted imidazole derivatives by accelerated ultrasonic irradiations. Compared to the other conventional catalysts which were used for the synthesis of imidazole derivatives, the green synthesis method for fabrication of this heterogeneous and magnetic nanocatalyst, its high thermal stability, being eco-friendly, noticeable efficiency and easy reusability have become privileges to be superior.
A recombinant platform to characterize the role of transmembrane protein hTMEM205 in Pt(ii)-drug resistance and extrusion
Authors: Gallenito Marc J , Qasim Tahir S , Tutol Jasmine N , Prakash Ved , Dodani Sheel C , Meloni Gabriele 
Published: July 2020

AbstractPlatinum-coordination complexes are among the most effective chemotherapeutic drugs used in clinics for the treatment of cancer. Despite their efficacy, cancer cells can develop drug resistance leading to treatment failure and relapse. Cellular uptake and extrusion of Pt(ii)-complexes mediated by transmembrane proteins are critical in controlling the intracellular concentration of Pt(ii)-drugs and in developing pre-target resistance. TMEM205 is a human transmembrane protein (hTMEM205) overexpressed in cancer cells that are resistant to cisplatin, but its molecular function underlying – resistance remains elusive. We developed a low-cost and high-throughput recombinant expression platform coupled to in vivo functional resistance assays to study the molecular mechanism by which the orphan hTMEM205 protects against Pt(ii)-complex toxicity. Based on the original observation by the Rosenberg group, which led to the discovery of cisplatin, we performed quantitative analysis of the effects of Pt(ii)-coordination complexes on cellular growth and filamentation in E. coli cells expressing hTMEM205. By coupling our methods with Pt quantification and cellular profiling in control and hTMEM205-expressing cells, we demonstrate that hTMEM205 mediates Pt(ii)-drug export selectively towards cisplatin and oxaliplatin but not carboplatin. By mutation analysis, we reveal that hTMEM205 recognizes and allows Pt(ii)-extrusion by a putative sulfur-based translocation mechanism, thereby resulting in pre-target resistance. Thus, hTMEM205 represents a new potential target that can be exploited to reduce cellular resistance towards Pt(ii)-drugs.
Antithrombotische Therapie bei akutem Koronarsyndrom und Vorhofflimmern
Authors: Darius Harald 
Published: July 2020

AbstractThe number of patients with atrial fibrillation (AF) is increasing due to the aging of the population. In addition, the number of patients with AF and an indication for oral anticoagulation (OAC) for the prevention of strokes increases, who are in need for a dual antiplatelet therapy (DAPT) with acetyl salicylic acid (ASA) plus a P2Y12-Inhibitor because of an acute coronary syndrome and/or coronary stent implantation. These patients did receive a triple therapy (TT) for 3–12 months in the past. Triple therapy never has been studied for efficacy or safety, however, the rate of bleeding complications in comparison to OAC or DAPT is significantly higher.Registries and smaller trials showed that dual therapy with an OAC plus a single platelet inhibitor may be sufficient to prevent strokes and stent thromboses/myocardial infarctions. Four prospective randomized trials involving all four NOACs (Non-Vitamin K oral anticoagulants) approved for stroke prevention in AF have been undertaken. The NOACs plus one antiplatelet agent were tested versus vitamin K-antagonists plus DAPT. In the meantime, the trials involving rivaroxaban (PIONEER AF-PCI), dabigatran (RE-DUAL PCI), apixaban (AUGUSTUS), and edoxaban (ENTRUST-AF-PCI) have been published. The current status is that a NOAC plus a single antiplatelet agent, mostly clopidogrel, is superior to TT with respect to the bleeding complications, without any obvious and statistically significant disadvantage for stroke rates or cardiac ischemic events. The international guidelines already recommend to treat with a NOAC and one antiplatelet agent instead of TT in case the patients bleeding risk is prevailing. Thus, TT seems not to be indicated anymore for most patients with AF and ACS or PCI.