bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adverse events reported to the U.S. Food and Drug Administration Adverse Event Reporting System for tisagenlecleucel
Authors: Dores Graça M. , Jason Christopher , Niu Manette T. , Perez‐Vilar Silvia 
Published: May 2021

AbstractThe U.S. Food and Drug Administration (FDA) approved the first chimeric antigen receptor T‐cell therapy, tisagenlecleucel, in August 2017. We sought to describe adverse events (AEs) reported to the FDA Adverse Event Reporting System (FAERS) for tisagenlecleucel in the post‐marketing period. We searched FAERS reports to identify U.S. patients treated with tisagenlecleucel between August 30, 2017‐August 31, 2019. We reviewed individual reports, calculated AE frequencies and reporting rates (RRs), and used Empirical Bayesian Geometric Mean methods to identify disproportionate reporting. We identified 646 de‐duplicated reports with a median age at AE of 18 (interquartile range: 11–56) years. The overall RR was 81.0%, and more than 95% of reports described a serious outcome. Cytokine release syndrome (CRS) was the most frequently reported AE (51.1%) with a RR of 41.4%; neurotoxicity was reported less frequently (21.2%), with a RR of 17.2%. Most disproportionately reported AEs were listed on the package insert or confounded by indication. We identified 13 subsequent neoplasms (SPN), the majority occurring within 6 months of tisagenlecleucel administration, and none reporting evidence of insertional mutagenesis. A total of 165 reports (26%) described a death outcome; most deaths occurred >30 days after treatment. The majority of deaths (64%) were due to progression of the underlying lymphoid neoplasm, and few (<5%) were attributed to CRS or neurotoxicity. We did not identify new safety concerns reported for tisagenlecleucel in the post‐marketing period. Reporting rates for CRS and neurotoxicity were lower than identified in the prelicensure clinical trials.
Chimeric antigen receptor T‐cells safety: A pharmacovigilance and meta‐analysis study
Authors: Dolladille Charles , Ederhy Stéphane , Ezine Emilien , Choquet Sylvain , Nguyen Lee S. , Alexandre Joachim , Moslehi Javid J. , Dechartres Agnès , Salem Joe‐Elie 
Published: May 2021

AbstractChimeric‐antigen‐receptor T cells directed against CD19 (CAR‐T) are emerging hematological therapeutics with scarce data on its overall safety profile spectrum. To determine the clinical features and incidence of adverse‐drug reactions (ADR) associated with CAR‐T. This observational, cross‐sectional, pharmacovigilance cohort study examined individual case safety reports from the World Health Organization database VigiBase and meta‐analysis of data from CAR‐T trials and cohorts in the literature was also performed through March, 2020. The primary objective was to identify ADR associated with approved CAR‐T (axicabtagene‐ciloleucel; tisagenlecleucel). We conducted a Bayesian disproportionate analysis with the 95% lower credibility‐interval of information component (IC025, significance > 0). We also performed a systematic‐review and meta‐analysis of CAR‐T trials and cohorts in the literature to evaluate ADR incidence. Nine ADR classes were associated with CAR‐T: Cytokine release syndrome (CRS, n = 1378, IC025 = 4.24), neurological disorders (n = 963, IC025 = 2.42), hematological disorders (n = 532, IC025 = 3.32), infections (n = 287, IC025 = 2.38), cardiovascular disorders (n = 256, IC025 = 2.81), pulmonary disorders (n = 186, IC025 = 3.80), reno‐metabolic disorders (n = 123, IC025 = 1.89), hemophagocytic‐lymphohistiocytosis (n = 36, IC025 = 5.01) and hepatic disorders (n = 32, IC025 = 2.49). ADR‐related fatalities accounted for 99/1783 (5.5%) of the reports and 262/1783 (14.7%) for all‐cause mortality. These ADR‐related fatalities were associated with hemophagocytic‐lymphohistiocytosis, cerebral vascular disorder, infections, and respiratory failure. In meta‐analyses, the most frequent any‐grade ADRs were CRS, hematological disorders, and neurological disorders. Fatal ADR were most found with neurological disorders, CRS, and infections. Note, CAR‐T infusion may be associated with severe ADR mainly following the week of administration, though rarely fatal. Infections, hemophagocytic‐lymphohistiocytosis and end organ failures including neurological or lung involvements require scrutiny.
Human cytogenetics at Johns Hopkins Hospital, 1959–1962
Authors: Ferguson‐Smith Malcolm A. 
Published: May 2021

AbstractAn account is given of the introduction of human cytogenetics to the Division of Medical Genetics at Johns Hopkins Hospital, and the first 3 years' work of the chromosome diagnostic laboratory that was established at the time. Research on human sex chromosome disorders, including novel discoveries in the Turner and Klinefelter syndromes, is described together with original observations on chromosome behavior at mitosis. It is written in celebration of the centenary of the birth of Victor McKusick, the acknowledged father of Medical Genetics, who established the Division and had the foresight to ensure that it included the investigation of human chromosomes.
Facet Selectivity Guided Assembly of Nanoarchitectures onto Two‐Dimensional Metal–Organic Framework Nanosheets
Authors: Li Zhihao , Gao Huajian , Shen Ruichen , Zhang Caixin , Li Leisi , Lv Yawei , Tang Liming , Du Yaping , Yuan Quan 
Published: May 2021

AbstractFacet‐selective nanostructures in living systems usually exhibit outstanding optical and enzymatic properties, playing important roles in photonics, matter exchange, and biocatalysis. Bioinspired construction of facet‐selective nanostructures offers great opportunities for sophisticated nanomaterials, but remains a formidable task. We have developed a macromolecule‐mediated strategy for the assembly of upconversion nanoparticles (UCNPs)/two‐dimensional metal–organic frameworks (2DMOFs) heterostructures with facet selectivity. Both experimental and theoretical results demonstrate that polyvinylpyrrolidone (PVP) can be utilized as an interface‐selective mediator to further promote the facet‐selective assembly of MOFs onto the surface of UCNPs. The UCNPs/2DMOFs nanostructures with facet selectivity display specific optical properties and show great advantages in anti‐counterfeiting. Our demonstration of UCNPs/2DMOFs provides a vivid example for the controlled fabrication of facet‐selective nanostructures and can promote the development of advanced functional materials for applications in biosensing, energy conversion, and information assurance.
A Top‐Down Strategy to Realize Surface Reconstruction of Small‐Sized Platinum‐Based Nanoparticles for Selective Hydrogenation
Authors: Jin Yu , Wang Pengtang , Mao Xinnan , Liu Shangheng , Li Leigang , Wang Lu , Shao Qi , Xu Yong , Huang Xiaoqing 
Published: May 2021

AbstractOver the past decades, despite the substantial efforts that have been devoted to the modifications of Pt nanoparticles (NPs) to tailor their selectivities for hydrogenation reactions, there are still a lack of facile strategies for precisely regulation of the surface properties of NPs, especially for those with small sizes. In this work, we propose a top‐down thermal annealing strategy for tuning the surface properties of Pt‐based NPs (≈4 nm) without the occurrence of aggregation. Compared to conventional bottom‐up methods, the present top‐down strategy can precisely regulate the surface compositions of Pt‐Cd NPs and other ternary Pt‐Cd‐M NPs (M=Fe, Ni, Co, Mn, and Sn). The optimized Pt‐Cd NPs exhibit excellent selectivity toward phenylacetylene and 4‐nitrostyrene hydrogenations with a styrene selectivity and 4‐aminophenyl styrene selectivity of 95.2 % and 94.5 %, respectively. This work provides a general strategy for the surface reconstructions of Pt‐based NPs, and promotes fundamental research on catalyst design for heterogeneous catalysis.
Creep resistance of linear low density polyethylene/carbonaceous hybrid nanocomposites: Experiments and modeling
Authors: Charitos Ilias , Kontou Evagelia 
Published: May 2021

AbstractIn the present work, the creep response of nanocomposites based on metallocene linear low density polyethylene (mLLDPE), reinforced with three types of carbonaceous nanofillers, namely carbon nanotubes (CNTs), graphene oxide (GO) platelets, and carbon nanofibers (CNFs) was experimentally studied. The effect of the nanofiller loading and the hybrid character of nanocomposites on the creep resistance of the nanocompsites was analyzed. In all cases, the creep resistance of the nanocomposites examined has been postulated. To support these results, creep has been modeled by a power creep law, while the creep‐ recovery modeling was achieved by a viscoelastic model. The implementation of the viscoelastic model has been made by assuming that the nanocomposite's structure can be represented by a physical network, with the dispersed nanofillers participating in the molecular rearrangements, which take place upon the imposition of stress. The time dependent constitutive equation involves a relaxation function, based on a Gaussian type distribution function, associated with the energy barriers that molecular segments need to overcome, for transitions to occur. It was found that creep‐recovery strain could be accurately captured with the same set of parameters, whereas the number of required model parameters was quite lower than that in the widely known viscoelastic models.
Improving fire behavior and smoke suppression of flame‐retardant PBS composites using lignin chelate as carbonization agent and catalyst
Authors: Yue Xiaopeng , Li Yu , Li Jian , Xu Yongjian 
Published: May 2021

AbstractA copolymer of alkali lignin and polyacrylamide was fabricated by graft copolymerization, and further chelated with Fe3+. The obtained lignin chelate with star structure was used as synergistic agent and catalyst with the incorporation of intumescent flame retardants (IFRs) to prepare flame‐retarded poly (butylene succinate) (PBS) composites. The replacement of IFR by lignin chelate favors the enhancement of mechanical performance, resulting in the synchronous improvement of tensile and flexural properties. Compared with the specimen used 25 wt% IFRs (75P/25I), the tensile strength, flexural strength, and modulus of specimen prepared by 23 wt% IFRs and 2 wt% lignin chelate (75P/23I/2LC) exhibited significant increased. A synergistic effect between IFR and lignin chelate occurred when they were combined with an appropriate ratio. When IFR and lignin chelate loadings were 24 and 1 wt%, respectively (75P/24I/1 LC), the limited oxygen index (LOI) value of 36.2% and UL‐94 V0 rate of composite could be achieved. Compared with 75P/25I, the char residue mass of 75P/24I/1 LC increased by 35.7%. Moreover, SEM images indicated that a more compact, smooth, and continuous char layer of 75P/24I/1 LC could be formed during combustion. The peak heat release rate (pHRR) and total heat release (THR) of 75P/24I/1 LC decreased by 58.9% and 9.9% compared with PBS, also decreased by 10.3% and 4.8% compared with 75P/25I, respectively. TGIR and FTIR analysis also indicated that lignin chelate exhibited an excellent synergistic effect with IFRs, and gave PBS a good flame retardancy by making contribution to char‐formation and gas‐phase flame retardancy. This study provides an alternative way for the application of natural polymers such as lignin in flame retardant materials.
Our contempt for weakness
Authors: Gullestad Siri Erika 
Published: May 2021

AbstractIn this paper, I explore the mental consequences of Covid‐19. Starting with the images of the pandemic – the intubated patient, the anonymous mass grave, and the death on FaceTime – images that express the horrendous threat of the coronavirus death, I emphasize that the pandemic reminds us of our vulnerability and existential dependence on the other. Based on examples, I discuss different reactions to Covid‐19 from a psychoanalytic perspective, specifically highlighting the mechanisms of denial, splitting and projection – the latter is illustrated in the scapegoating of the pandemic, for example, blaming China, the immigrants or youth parties. I argue that a common characteristic of those different defense mechanisms may be a contempt for weakness – as demonstrated when coronavirus deniers and Proud Boys are marching together. The paper also examines the importance of structure and the consequences of the loss of everyday structure – be it job, school, peer groups, training studios, senior centers, or culture. I conclude by emphasizing that the pandemic has taught us how dependent we are on each other – and that it should inspire us to greater tolerance for vulnerability, and less contempt for weakness.
On observability analysis and observer design for a class of nonlinear uncertain systems with general elastic vibration dynamics
Authors: Zhang Xiaoyan , Xue Wenchao , Zhao Yanlong 
Published: May 2021

AbstractThis paper focuses on the observability analysis for a general class of rigid‐flexible coupling systems constituted of rigid‐body mode and elastic vibration modes with uncertain dynamics and disturbances. And the measured output is a linear combination of rigid‐body mode and elastic vibration modes. Firstly, the necessary and sufficient condition of the observability for such system is given. Secondly, the general extended state observer design is proposed to estimate the states of both rigid‐body mode and elastic vibration modes as well as “total disturbance.” Next, the convergence of estimation errors of the general extended state observer is discussed. Then, under unobservable case, a compressed extended state observer is designed to estimate the states and the “total disturbance” acting on rigid‐body mode, and the corresponding estimation errors are studied. In addition, the theoretical results are demonstrated via the simulation on a rigid‐flexible coupling system.
Circalunar clocks—Old experiments for a new era
Authors: Kaiser Tobias S. , Neumann Jule 
Published: May 2021

AbstractCircalunar clocks, which allow organisms to time reproduction to lunar phase, have been experimentally proven but are still not understood at the molecular level. Currently, a new generation of researchers with new tools is setting out to fill this gap. Our essay provides an overview of classic experiments on circalunar clocks. From the unpublished work of the late D. Neumann we also present a novel phase response curve for a circalunar clock. These experiments highlight avenues for molecular work and call for rigor in setting up and analyzing the logistically complex experiments on circalunar clocks. Re‐evaluating classic experiments, we propose that (1) circalunar clocks in different organisms will have divergent mechanisms and physiological bases, (2) they may have properties very different from the well‐studied circadian clocks and (3) they may have close mechanistic and molecular relations to seasonal rhythms and diapause.
Proteomics and metabolomics analyses reveal the full spectrum of inflammatory and lipid metabolic abnormalities in dyslipidemia
Authors: Du Hui , Rao Yifei , Liu Ronghua , Deng Kesui , Guan Yongmei , Luo Dewei , Mao Qiping , Yu Jianwei , Bo Tao , Fan Ziquan , Ouyang Hui , Feng Yulin , Zhu Weifeng 
Published: May 2021

AbstractDyslipidemia is a common, chronic metabolic disease associated with cardiovascular complications. Due to the multiplicity of etiological factors, the pathogenesis of dyslipidemia is still unclear. In this study, we combined proteomics and metabolomics methods to analyze the plasma of patients with dyslipidemia and healthy subjects. isobaric tags for relative and absolute quantification (iTRAQ) markers, combined with LC–MS/MS proteomics technology and the UHPLC/Orbitfast‐X Tribrid system, were used to establish the metabolite profile in clinical dyslipidemia. A total of 137 differentially expressed proteins, mainly related to biological processes such as protein activation cascades, adaptive immune responses, complement activation, acute inflammatory responses, and regulation of acute inflammatory responses, were identified. These proteins are involved in the regulation of important metabolic pathways, such as immunity and inflammation, coagulation and hemostasis, lipid metabolism, and oxidation and antioxidant defenses. The analysis of clinical metabolites showed there were 69 different metabolites in plasma, mainly related to glycerolipid, sphingolipid, porphyrin, α‐linolenic acid, linoleic acid, and arachidonic acid metabolism, suggesting that the regulation of inflammation and lipid metabolism may be disturbed in patients with dyslipidemia. Among these, significant changes were observed in indole‐3‐propionic acid (IPA), which is considered as a potential biomarker of dyslipidemia. The combined analysis of proteins and metabolites showed that arachidonic acid, linoleic acid, and lipid metabolic pathways were closely related to dyslipidemia. IPA may be a potential biomarker. The information provided in this study may provide new insights into the pathogenesis of animal models of dyslipidemia and related disease models, as well as potential intervention targets.
Upregulation of P53 promotes nucleus pulposus cell apoptosis in intervertebral disc degeneration through upregulating NDRG2
Authors: Zhang Kejie , Zhang Yuanbin , Zhang Cong , Zhu Limin 
Published: May 2021

AbstractP53 is an apoptosis marker which is involved in determining nucleus pulposus (NP) cell fate. Little is known about P53 interaction with N‐Myc downstream‐regulated gene 2 (NDRG2) in intervertebral disc degeneration (IVDD). Here, we studied the role of the P53‐NDRG2 axis in IVDD. We found that NDRG2 was expressed in NP tissue obtained from patients with IVDD. The level of NDRG2 was positively related to the severity of IVDD, as determined by Pfirrmann grading. Subsequently, we overexpressed NDRG2 in human NP cells by adenoviral transfection and studied the effects of increased levels of NDRG2 on the viability and apoptosis of these cells. NDRG2 overexpression induced NP cell apoptosis and reduced viability in NP cells obtained from patient with IVDD. We also found that the level of P53 was elevated in NP cells from patients with IVDD and treatment with exogenous P53 upregulated NDRG2 in NP cells. Last, IVDD model was established in P53 knockout mice and the pathological changes in the intervertebral discs and NDRG2 expression were examined. P53 knockout can reduce the damage of NP tissues after IVDD surgery to some extent. Restoration of NDRG2 antagonized the effect of P53 knockout on IVDD. Collectively, this study suggests that elevated P53 in NP cells stimulates apoptosis of the cells by upregulating NDRG2 expression, thereby exacerbating IVDD.
Ethylcyclohexane Hydroconversion in EU‐1 Zeolite: DFT‐based Microkinetic Modeling Reveals the Nature of the Kinetically Relevant Intermediates
Authors: Gutierrez‐Acebo Ester , Rey Jérôme , Bouchy Christophe , Schuurman Yves , Chizallet Céline 
Published: May 2021

AbstractThe transformation of cycloalkanes is a key‐reaction in refining and petrochemistry. Herein, we unravel the mechanism and the kinetics of the transformation of ethylcyclohexane, considering a bifunctional catalyst composed of platinum and of the EU‐1 zeolite, by experiments, density functional theory (DFT) calculations and DFT‐based microkinetic modeling. The simulated mechanisms involve carbenium intermediates. DFT shows the central kinetic role of the π‐complexes corresponding to secondary carbenium ions. Cycle contractions and expansions appear to be rate‐limiting. The DFT‐based microkinetic model includes a limited number of kinetic parameters optimized by regression with respect to the experimental data. The agreement with experimental results is very good, showing that the mechanisms proposed, the nature of the intermediates, and the values of the computed rate constants, are relevant. The reaction starts by the cycle contraction of 1‐ethylcyclohexene, then shifts to a second sequence of cycle expansion‐contraction reactions by intercalated methyl‐shifts.
Direct Conversion of 5‐Hydroxymethylfurfural to Furanic Diether by Copper‐Loaded Hierarchically Structured ZSM‐5 Catalyst in a Fixed‐Bed Reactor
Authors: Hu Hualei , Xue Tingting , Zhang Zhenxin , Gan Jiang , Chen Liangqi , Zhang Jian , Qu Fengzuo , Cai Weijie , Wang Lei 
Published: May 2021

AbstractThe highly‐efficient conversion of 5‐hydroxymethylfurfural (HMF) to 2,5‐bis(ethoxymethyl)furan (BEMF) was achieved over the copper‐loaded hierarchically structured ZSM‐5 (Cu/HSZ) catalysts in the continuous fixed‐bed reactor. The main reaction path for BEMF synthesis on the Cu/HSZ catalysts was confirmed as following: HMF was firstly hydrogenated to BHMF intermediates over metal sites and then the formed BHMF was etherified by acid sites. Benefiting from the ammonia evaporation (AE) method promoted the dispersion of copper and reduced the acidity, the Cu/HSZ‐AE catalyst exhibited more excellent BEMF yield and stability than the catalyst prepared by conventional incipient‐wetness impregnation (Cu/HSZ‐IW). Indeed, the inactivation of Cu/HSZ‐IW catalyst was mainly attributed to the deactivation of copper by carbon species deposition.
Hydrochloric Acid‐Assisted Regeneration of Cobalt Ethylenediamine for NOx Remediation in Flue Gas
Authors: Yang Jie , Liu Shengyu , Fu Qianwen , Li-Chao Nengzi , Chen Li 
Published: May 2021

AbstractCobalt ethylenediamine ([Co(en)3]3+) is widely used for NOx remediation in flue gas. However, its industrial applications are limited due to the lack of an efficient regeneration method that converts Co3+ to Co2+. Here, hydrogen chloride is applied as an additive and the performance of cobalt ethylenediamine under variable flue gas compositions is analyzed. The results demonstrate that low pH values favor the conversion of Co3+ to Co2+. Further, a reaction temperature of 100 °C and more than three minutes reaction time were found to accelerate the reduction of Co3+. The NOx removal efficiency could reach more than 70 % after the first regeneration. After 23 consecutive days of continuous experiments, the denitration efficiency of flue gas could be as high as 60 % or more.
Low‐Temperature H2 Reduction of Copper Oxide Subnanoparticles
Authors: Sonobe Kazutaka , Tanabe Makoto , Imaoka Takane , Chun Wang‐Jae , Yamamoto Kimihisa 
Published: May 2021

AbstractInvited for the cover of this issue is Kimihisa Yamamoto and co‐workers at Tokyo Institute of Technology and International Christian University. The image depicts enhanced reactivity of the copper oxide subnanoparticles under low‐temperature conditions. Read the full text of the article at 10.1002/chem.202100508.
Exploring the Pyrolysis Mechanism towards OER Performance Optimization of Salophen‐ligated Binuclear Cobalt Complex†
Authors: An Qi , Pan Bingxin , Li Li , Peng Xu , Zeng Ming‐Hua 
Published: May 2021

Main observation and conclusionExploring pyrolysis process is an efficient way to study the relationship between molecular level of the precursor structure and electrocatalytic functional materials in practice. Here, the unique semi‐enclosed sector structure of Salophen ligands with highly symmetric N, N, O, O mode was introduced to construct binuclear Co complex [Co2(salophen)(Cl)2(C2H3N)] (compound 1), which provides preliminary theoretical basis for the efficient coreshell structure electrocatalysts obtained by pyrolysis regulation. Moreover, we adopted TG‐MS to real‐time track the pyrolysis process from precursors of binuclear Co complexes with Salophen ligand to efficient catalytic materials with core‐shell nanostructures. As expected, the 1‐600 sample achieves ultra‐low overpotential of 256 mV at 10 mA·cm–2 and high catalytic stability within 10 h in 1 mol/L KOH solution. This work highlights salophen‐ligated complex as excellent precursor material system for the analysis of pyrolysis evolution process, and provides an opportunity for targeted preparation of efficient oxygen evolution reaction (OER) nanocatalysts.