bluuebunny/crossref_metadata_2025 huggingface dataset:
Poly(GP), neurofilament and grey matter deficits in C9orf72 expansion carriers
Authors: Meeter Lieke H.H. , Gendron Tania F. , Sias Ana C. , Jiskoot Lize C. , Russo Silvia P. , Donker Kaat Laura , Papma Janne M. , Panman Jessica L. , van der Ende Emma L. , Dopper Elise G. , Franzen Sanne , Graff Caroline , Boxer Adam L. , Rosen Howard J. , Sanchez‐Valle Raquel , Galimberti Daniela , Pijnenburg Yolande A. L. , Benussi Luisa , Ghidoni Roberta , Borroni Barbara , Laforce Robert , del Campo Marta , Teunissen Charlotte E. , van Minkelen Rick , Rojas Julio C. , Coppola Giovanni , Geschwind Dan H. , Rademakers Rosa , Karydas Anna M. , Öijerstedt Linn , Scarpini Elio , Binetti Giuliano , Padovani Alessandro , Cash David M. , Dick Katrina M. , Bocchetta Martina , Miller Bruce L. , Rohrer Jonathan D. , Petrucelli Leonard , van Swieten John C. , Lee Suzee E.
Published: April 2018

Objective

To evaluate poly(GP), a dipeptide repeat protein, and neurofilament light chain (NfL) as biomarkers in presymptomatic C9orf72 repeat expansion carriers and patients with C9orf72‐associated frontotemporal dementia. Additionally, to investigate the relationship of poly(GP) with indicators of neurodegeneration as measured by NfL and grey matter volume.

Methods

We measured poly(GP) and NfL levels in cerebrospinal fluid (CSF) from 25 presymptomatic C9orf72 expansion carriers, 64 symptomatic expansion carriers with dementia, and 12 noncarriers. We explored associations with grey matter volumes using region of interest and voxel‐wise analyses.

Results

Poly(GP) was present in C9orf72 expansion carriers and absent in noncarriers (specificity 100%, sensitivity 97%). Presymptomatic carriers had lower poly(GP) levels than symptomatic carriers. NfL levels were higher in symptomatic carriers than in presymptomatic carriers and healthy noncarriers. NfL was highest in patients with concomitant motor neuron disease, and correlated with disease severity and survival. Associations between poly(GP) levels and small grey matter regions emerged but did not survive multiple comparison correction, while higher NfL levels were associated with atrophy in frontotemporoparietal cortices and the thalamus.

Interpretation

This study of C9orf72 expansion carriers reveals that: (1) poly(GP) levels discriminate presymptomatic and symptomatic expansion carriers from noncarriers, but are not associated with indicators of neurodegeneration; and (2) NfL levels are associated with grey matter atrophy, disease severity, and shorter survival. Together, poly(GP) and NfL show promise as complementary biomarkers for clinical trials for C9orf72‐associated frontotemporal dementia, with poly(GP) as a potential marker for target engagement and NfL as a marker of disease activity and progression.
Hybrid online learning control in networked multiagent systems: A survey
Authors: Poveda Jorge I. , Benosman Mouhacine , Teel Andrew R.
Published: April 2018

This survey paper studies deterministic control systems that integrate three of the most active research areas during the last years: (1) online learning control systems, (2) distributed control of networked multiagent systems, and (3) hybrid dynamical systems (HDSs). The interest for these types of systems has been motivated mainly by two reasons: First, the development of cheap massive computational power and advanced communication technologies, which allows to carry out large computations in complex networked systems, and second, the recent development of a comprehensive theory for HDSs that allows to integrate continuous‐time dynamical systems and discrete‐time dynamical systems in a unified manner, thus providing a unifying modeling language for complex learning‐based control systems. In this paper, we aim to give a comprehensive survey of the current state of the art in the area of online learning control in multiagent systems, presenting an overview of the different types of problems that can be addressed, as well as the most representative control architectures found in the literature. These control architectures are modeled as HDSs, which include as special subsets continuous‐time dynamical systems and discrete‐time dynamical systems. We highlight the different advantages and limitations of the existing results as well as some interesting potential future directions and open problems.
2D/2D Heterojunction of Ultrathin MXene/Bi2WO6 Nanosheets for Improved Photocatalytic CO2 Reduction
Authors: Cao Shaowen , Shen Baojia , Tong Tong , Fu Junwei , Yu Jiaguo
Published: April 2018

Exploring cheap and efficient cocatalysts for enhancing the performance of photocatalysts is a challenge in the energy conversion field. Herein, 2D ultrathin Ti3C2 nanosheets, a kind of MXenes, are prepared by etching Ti3AlC2 with subsequent ultrasonic exfoliation. A novel 2D/2D heterojunction of ultrathin Ti3C2/Bi2WO6 nanosheets is then successfully prepared by in situ growth of Bi2WO6 ultrathin nanosheets on the surface of these Ti3C2 ultrathin nanosheets. The resultant Ti3C2/Bi2WO6 hybrids exhibit a short charge transport distance and a large interface contact area, assuring excellent bulk‐to‐surface and interfacial charge transfer abilities. Meanwhile, the improved specific surface area and pore structure endow Ti3C2/Bi2WO6 hybrids with an enhanced CO2 adsorption capability. As a result, the 2D/2D heterojunction of ultrathin Ti3C2/Bi2WO6 nanosheets shows significant improvement on the performance of photocatalytic CO2 reduction under simulated solar irradiation. The total yield of CH4 and CH3OH obtained on the optimized Ti3C2/Bi2WO6 hybrid is 4.6 times that obtained on pristine Bi2WO6 ultrathin nanosheets. This work provides a new protocol for constructing 2D/2D photocatalytic systems and demonstrates Ti3C2 as a promising and cheap cocatalyst.
Field Emission of Electrons Powered by a Triboelectric Nanogenerator
Authors: Zi Yunlong , Wu Changsheng , Ding Wenbo , Wang Xingfu , Dai Yejing , Cheng Jia , Wang Jiyu , Wang Zhengjun , Wang Zhong Lin
Published: April 2018

Field emission of electrons usually requires high voltage (HV) of at least 100 V, which limits its applications due to the high cost, instability, portability issues, etc., of the HV instrument. Triboelectric nanogenerators (TENGs) have been developed to provide an HV of at least several kV for portable/mobile instrument, with controllability already demonstrated. Here, the field emission of electrons driven by TENG, namely, tribo‐field emission, is presented for the first time. The emission voltage and the charge transfer per cycle can be tuned and controlled by TENG. The current peak generated from TENG with limited charge transfer is demonstrated to be more favorable than the direct current HV source in terms of emitter protection. A unidirectional continuous emission current is achieved through the tribo‐field emission. A cathode‐ray tube can be powered by TENG, with hours of illumination demonstrated through only one sliding motion. Such approach can provide a potential solution for controllable, stable, and portable field‐emission devices without any additional external power sources.
Auxetic Cardiac Patches with Tunable Mechanical and Conductive Properties toward Treating Myocardial Infarction
Authors: Kapnisi Michaella , Mansfield Catherine , Marijon Camille , Guex Anne Geraldine , Perbellini Filippo , Bardi Ifigeneia , Humphrey Eleanor J. , Puetzer Jennifer L. , Mawad Damia , Koutsogeorgis Demosthenes C. , Stuckey Daniel J. , Terracciano Cesare M. , Harding Sian E. , Stevens Molly M.
Published: April 2018

An auxetic conductive cardiac patch (AuxCP) for the treatment of myocardial infarction (MI) is introduced. The auxetic design gives the patch a negative Poisson's ratio, providing it with the ability to conform to the demanding mechanics of the heart. The conductivity allows the patch to interface with electroresponsive tissues such as the heart. Excimer laser microablation is used to micropattern a re‐entrant honeycomb (bow‐tie) design into a chitosan‐polyaniline composite. It is shown that the bow‐tie design can produce patches with a wide range in mechanical strength and anisotropy, which can be tuned to match native heart tissue. Further, the auxetic patches are conductive and cytocompatible with murine neonatal cardiomyocytes in vitro. Ex vivo studies demonstrate that the auxetic patches have no detrimental effect on the electrophysiology of both healthy and MI rat hearts and conform better to native heart movements than unpatterned patches of the same material. Finally, the AuxCP applied in a rat MI model results in no detrimental effect on cardiac function and negligible fibrotic response after two weeks in vivo. This approach represents a versatile and robust platform for cardiac biomaterial design and could therefore lead to a promising treatment for MI.
Glycera‐Inspired Synergistic Interfacial Interactions for Constructing Ultrastrong Graphene‐Based Nanocomposites
Authors: Cheng Yiren , Peng Jingsong , Xu Hanjie , Cheng Qunfeng
Published: April 2018

The interest in bioinspired graphene‐based nanocomposites (BGBNs) is rising recently due to their exceptional mechanical properties as well as high electrical conductivities. Numerous works have suggested that the synergistic interfacial design of ionic bonding (IB) co‐working with other interfacial interactions effectively improves the mechanical properties of BGBNs. However, as the ions are conventionally chelated with graphene oxide (GO) nanosheets, the relatively weak and short interlayered IB may hinder the load transfer between GO nanosheets leading to poor synergistic effects. Herein, inspired by the jaw of Glycera, the synergistic effect is further amplified via special IB, which stiffens the organic component. Compared with the traditional IB, the metal–ligand coordinate bonding by copper ions that is used in this work and originates from Glycera, selectively cross‐links the chitosan chains. This Glycera‐inspired synergistic effect strategy boosts record tensile strength to an extraordinary value of 868.6 MPa, five times higher than that of the pure reduced graphene oxide film. The additional high electrical conductivity enables applications in many fields such as flexible energy devices, supercapacitors, and other electronic devices.
Photopolymerized Triazole‐Based Glassy Polymer Networks with Superior Tensile Toughness
Authors: Song Han Byul , Baranek Austin , Worrell Brady T. , Cook Wayne D. , Bowman Christopher N.
Published: April 2018

Photopolymerization is a ubiquitous, indispensable technique widely applied in applications from coatings, inks, and adhesives to thermosetting restorative materials for medical implants, and the fabrication of complex macroscale, microscale, and nanoscale 3D architectures via additive manufacturing. However, due to the brittleness inherent in the dominant acrylate‐based photopolymerized networks, a significant need exists for higher performance resin/oligomer formulations to create tough, defect‐free, mechanically ductile, thermally and chemically resistant, high modulus network polymers with rapid photocuring kinetics. This study presents densely cross‐linked triazole‐based glassy photopolymers capable of achieving preeminent toughness of ≈70 MJ m−3 and 200% strain at ambient temperature, comparable to conventional tough thermoplastics. Formed either via photoinitiated copper(I)‐catalyzed cycloaddition of monomers containing azide and alkyne groups (CuAAC) or via photoinitiated thiol‐ene reactions from monomers containing triazole rings, these triazole‐containing thermosets completely recover their original dimensions and mechanical behavior after repeated deformations of 50% strain in the glassy state over multiple thermal recovery–strain cycles.
Configurable Integration of On‐Chip Quantum Dot Lasers and Subwavelength Plasmonic Waveguides
Authors: Rong Kexiu , Gan Fengyuan , Shi Kebin , Chu Saisai , Chen Jianjun
Published: April 2018

The integration of on‐chip dielectric lasers and subwavelength plasmonic waveguides has attracted enormous attention because of the combination of both the advantages of the high performances of the small dielectric lasers and the subwavelength plasmonic waveguides. However, the configurable integration is still a challenge owing to the complexity of the hybrid structures and the damageability of the gain media in the multistep micro/nanofabrications. By employing the dark‐field optical imaging technique with a position uncertainty of about 21 nm and combining the high‐resolution electron beam lithography, the small colloidal quantum dot (CQD) lasers without any damages are accurately aligned with the silver nanowires. As a result, the integration of the CQD lasers and the silver nanowires can be flexibly configured on chips. In the experiment, the tangential coupling, radial coupling, and complex coupling between the high‐performance CQD lasers and the subwavelength silver nanowires are demonstrated. Because of the subwavelength field confinements of the silver nanowires, the deep‐subwavelength coherent sources (multimode, one‐color single‐mode, or two‐color single‐mode) with a mode area of only 0.008λ2 are output from these hybrid structures. This configurable on‐chip integration with high flexibility and controllability will greatly facilitate the developments of the complex functional hybrid photonic–plasmonic circuits.
Melt Electrospinning Writing of Highly Ordered Large Volume Scaffold Architectures
Authors: Wunner Felix M. , Wille Marie‐Luise , Noonan Thomas G. , Bas Onur , Dalton Paul D. , De‐Juan‐Pardo Elena M. , Hutmacher Dietmar W.
Published: April 2018

The additive manufacturing of highly ordered, micrometer‐scale scaffolds is at the forefront of tissue engineering and regenerative medicine research. The fabrication of scaffolds for the regeneration of larger tissue volumes, in particular, remains a major challenge. A technology at the convergence of additive manufacturing and electrospinning–melt electrospinning writing (MEW)–is also limited in thickness/volume due to the accumulation of excess charge from the deposited material repelling and hence, distorting scaffold architectures. The underlying physical principles are studied that constrain MEW of thick, large volume scaffolds. Through computational modeling, numerical values variable working distances are established respectively, which maintain the electrostatic force at a constant level during the printing process. Based on the computational simulations, three voltage profiles are applied to determine the maximum height (exceeding 7 mm) of a highly ordered large volume scaffold. These thick MEW scaffolds have fully interconnected pores and allow cells to migrate and proliferate. To the best of the authors knowledge, this is the first study to report that z‐axis adjustment and increasing the voltage during the MEW process allows for the fabrication of high‐volume scaffolds with uniform morphologies and fiber diameters.
Deep‐Ultraviolet Hyperbolic Metacavity Laser
Authors: Shen Kun‐Ching , Ku Chen‐Ta , Hsieh Chiieh , Kuo Hao‐Chung , Cheng Yuh‐Jen , Tsai Din Ping
Published: April 2018

Given the high demand for miniaturized optoelectronic circuits, plasmonic devices with the capability of generating coherent radiation at deep subwavelength scales have attracted great interest for diverse applications such as nanoantennas, single photon sources, and nanosensors. However, the design of such lasing devices remains a challenging issue because of the long structure requirements for producing strong radiation feedback. Here, a plasmonic laser made by using a nanoscale hyperbolic metamaterial cube, called hyperbolic metacavity, on a multiple quantum‐well (MQW), deep‐ultraviolet emitter is presented. The specifically designed metacavity merges plasmon resonant modes within the cube and provides a unique resonant radiation feedback to the MQW. This unique plasmon field allows the dipoles of the MQW with various orientations into radiative emission, achieving enhancement of spontaneous emission rate by a factor of 33 and of quantum efficiency by a factor of 2.5, which is beneficial for coherent laser action. The hyperbolic metacavity laser shows a clear clamping of spontaneous emission above the threshold, which demonstrates a near complete radiation coupling of the MQW with the metacavity. This approach shown here can greatly simplify the requirements of plasmonic nanolaser with a long plasmonic structure, and the metacavity effect can be extended to many other material systems.
Materials and Techniques for Implantable Nutrient Sensing Using Flexible Sensors Integrated with Metal–Organic Frameworks
Authors: Ling Wei , Liew Guoguang , Li Ya , Hao Yafeng , Pan Huizhuo , Wang Hanjie , Ning Baoan , Xu Hang , Huang Xian
Published: April 2018

The combination of novel materials with flexible electronic technology may yield new concepts of flexible electronic devices that effectively detect various biological chemicals to facilitate understanding of biological processes and conduct health monitoring. This paper demonstrates single‐ or multichannel implantable flexible sensors that are surface modified with conductive metal–organic frameworks (MOFs) such as copper‐MOF and cobalt‐MOF with large surface area, high porosity, and tunable catalysis capability. The sensors can monitor important nutriments such as ascorbicacid, glycine, l‐tryptophan (l‐Trp), and glucose with detection resolutions of 14.97, 0.71, 4.14, and 54.60 × 10−6 m, respectively. In addition, they offer sensing capability even under extreme deformation and complex surrounding environment with continuous monitoring capability for 20 d due to minimized use of biological active chemicals. Experiments using live cells and animals indicate that the MOF‐modified sensors are biologically safe to cells, and can detect l‐Trp in blood and interstitial fluid. This work represents the first effort in integrating MOFs with flexible sensors to achieve highly specific and sensitive implantable electrochemical detection and may inspire appearance of more flexible electronic devices with enhanced capability in sensing, energy storage, and catalysis using various properties of MOFs.
Cholesteric Metronomes with Flexoelectrically Programmable Amplitude
Authors: Joshi Vinay , Chang Kai‐Han , Varanytsia Andrii , Paterson Daniel A. , Storey John M. D. , Imrie Corrie T. , Chien Liang‐Chy
Published: April 2018

Replicating natural phenomena using soft material actuators is a major challenge for material scientists. For example, a metronome is a device that produces an audible beat at a selected interval. In anisotropic soft materials, a flexoelectrically‐driven cholesteric liquid crystal (CLC) can display a metronome‐like swinging effect when an applied electric field is normal to the helices of a CLC that are aligned normal to the substrates. The amplitude and direction of swing of a flexoelectrically‐driven CLC is electrically programmable. Combining a bimesogen and a CLC with an optimized helical pitch, the mixture enables a large flexoelastic ratio (e/K= 2.758 CN‐1m‐1) and swinging amplitude of 53°. Furthermore, assisted by polymer stabilization the composite mixture offers many benefits of electro‐optical characteristics including fast response time (425 µs) and high optical contrast (500:1) between the field‐on and field‐off states as well as wavelength‐independent transmittance. The advances in the flexoelectro‐optical behavior of cholesteric metronomes open new avenues for applications in information displays, sensors and photonic devices.
Integrating the Emitter and Host Characteristics of Donor–Acceptor Systems through Edge‐Spiro Effect Toward 100% Exciton Harvesting in Blue and White Fluorescence Diodes
Authors: Lv Xialei , Zhang Wenzhi , Ding Dongxue , Han Chunmiao , Huang Zhi , Xiang Songpo , Zhang Qing , Xu Hui , Wang Lei
Published: April 2018

Herein, by utilizing edge‐spiro effect to modulate intramolecular charge transfer and intermolecular interactions, emitter and host characteristic are integrated in simple donor–acceptor systems named SFInxTz. As emitter, SFI34pTz realizes true‐blue thermally activated delayed fluorescent (TADF) diodes with an external quantum efficiency (EQE) of 25.3% and Commission Internationale de L'Eclairage (CIE) coordinates of (0.15, 0.20). As host, it can endow the yellow devices with the maximum EQE about 18%. When SFI34pTz serves as both blue emitter and yellow host material in pure fluorescence white device, the maximum efficiencies are as high as 22.9% for EQE and 52.4 lm W−1 for power efficiency, and stable electroluminescence spectra are successfully realized with CIE coordinates of (0.32 ± 0.01, 0.42 ± 0.02). Above all, SFI34pTz manifests the effectiveness of the edge‐spiro strategy in developing host‐featured blue TADF dyes for high‐performance blue devices and white organic light‐emitting diodes (WOLEDs). More importantly, a novel blue–orange–blue sandwich device structure consisting of all‐TADF materials for high‐efficiency pure fluorescence WOLEDs is proposed.
Iridium‐Catalyzed Tandem Cyclization of Benzoylacetonitriles with Diazo Compounds Leading to Substituted Naphtho[1,8‐bc]pyrans by Sequential C−H Functionalization
Authors: Yan Kelu , Li Bin , Wang Baiquan
Published: April 2018

The cascade annulation reactions of benzoylacetonitriles with diazo compounds proceed efficiently in the presence of an iridium catalyst to give substituted naphtho[1,8‐bc]pyrans by sequential cleavage of C(sp2)−H/C(sp3)−H and C(sp2)−H/O−H bonds. Interestingly, the reactions involving cyclic diazo compounds and open‐chain diazo compounds lead to different types of naphtho[1,8‐bc]pyrans. Most products are obtained in moderate to good yields with a broad range of substrates.

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Co‐doped ZnO thin films grown by pulsed electron beam ablation as model nano‐catalysts in fischer‐tropsch synthesis
Authors: Ali Asghar , Henda Redhouane , Aluha James , Abatzoglou Nicolas
Published: April 2018

A single‐step deposition of cobalt‐doped zinc oxide (Co‐ZnO) thin film nano‐composites on three different crystalline substrates, viz., Al2O3 (c‐sapphire), silicon (100) (Si), and SiO2 (quartz) is reported, using pulsed electron beam ablation (PEBA). The results indicate that the type of substrate has no effect on Co‐ZnO films stoichiometry, morphology, microstructure, and film thickness. The findings show the presence of hexagonal close‐packed metallic Co whose content increases in the films deposited on Al2O3 and Si substrates relatively to SiO2 substrate. The potential of the films as model nano‐catalysts has been evaluated in the context of the Fischer‐Tropsch (FT) process. Fuel fractions, which have been observed in FT liquid products, are rich in diesel and waxes. Specifically, Co‐ZnO/Al2O3 nano‐catalyst shows a selectivity of ∼4%, 31%, and 65% towards gasoline, diesel, and waxes, respectively, while Co‐ZnO/SiO2 nano‐catalyst shows a selectivity of ∼12%, 51%, and 37%, for gasoline, diesel, and waxes, respectively. © 2018 American Institute of Chemical Engineers AIChE J, 64: 3332–3340, 2018
Hodgkin lymphoma: 2018 update on diagnosis, risk‐stratification, and management
Authors: Ansell Stephen M.
Published: April 2018

Disease Overview

Hodgkin lymphoma (HL) is an uncommon B‐cell lymphoid malignancy affecting 8500 new patients annually and representing approximately 10.2% of all lymphomas in the United States.

Diagnosis

HL is composed of two distinct disease entities: classical HL and nodular lymphocyte predominant HL. Nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte‐rich HL are subgroups of classical HL.

Risk Stratification

An accurate assessment of the stage of disease in patients with HL is critical for the selection of the appropriate therapy. Prognostic models that identify patients at low or high risk for recurrence, as well as the response to therapy as determined by positron emission tomography scan, are used to optimize therapy.

Risk‐Adapted Therapy

Initial therapy for HL patients is based on the histology of the disease, the anatomical stage and the presence of poor prognostic features. Patients with early stage disease are typically treated with combined modality strategies utilizing abbreviated courses of combination chemotherapy followed by involved‐field radiation therapy, while those with advanced stage disease receive a longer course of chemotherapy often without radiation therapy. Newer agents including brentuximab vedotin are now being incorporated into frontline therapy and these new combinations are becoming a standard of care.

Management of Relapsed/Refractory Disease

High‐dose chemotherapy (HDCT) followed by an autologous stem cell transplant (ASCT) is the standard of care for most patients who relapse following initial therapy. For patients who fail HDCT with ASCT, brentuximab vedotin, PD‐1 blockade, nonmyeloablative allogeneic transplant or participation in a clinical trial should be considered.
The effect of iron chelation therapy on overall survival in sickle cell disease and β‐thalassemia: A systematic review
Authors: Ballas Samir K. , Zeidan Amer M. , Duong Vu H. , DeVeaux Michelle , Heeney Matthew M.
Published: April 2018

Red blood cell transfusions have become standard of care for the prevention of life‐threatening anemia in patients with β‐thalassemia and sickle cell disease (SCD). However, frequent transfusions can lead to accumulation of iron that can result in liver cirrhosis, diabetes mellitus, arthritis, arrhythmias, cardiomyopathy, heart failure, and hypogonadotropic hypogonadism. Iron chelation therapy has been shown to reduce serum ferritin levels and liver iron content, but limitations of trial design have prevented any demonstration of improved survival. The objective of this systematic review was to investigate the impact of iron chelation therapy on overall and event‐free survival in patients with β‐thalassemia and SCD. Eighteen articles discussing survival in β‐thalassemia and 3 in SCD were identified. Overall iron chelation therapy resulted in better overall survival, especially if it is instituted early and compliance is maintained. Comparative studies did not show any significant differences between available iron chelation agents, although there is evidence that deferiprone is better tolerated than deferoxamine and that compliance is more readily maintained with the newer oral drugs, deferiprone and deferasirox. Iron chelation therapy, particularly the second‐generation oral agents, appears to be associated with improved overall and event‐free survival in transfusion‐dependent patients with β‐thalassemia and patients with SCD.
Potent anti‐leukemia activities of humanized CD19‐targeted Chimeric antigen receptor T (CAR‐T) cells in patients with relapsed/refractory acute lymphoblastic leukemia
Authors: Cao Jiang , Wang Gang , Cheng Hai , Wei Chen , Qi Kunming , Sang Wei , Zhenyu Li , Shi Ming , Li Huizhong , Qiao Jianlin , Pan Bin , Zhao Jing , Wu Qingyun , Zeng Lingyu , Niu Mingshan , Jing Guangjun , Zheng Junnian , Xu Kailin
Published: April 2018

Chimeric antigen receptor T (CAR‐T) cell therapy has shown promising results for relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL). The immune response induced by murine single‐chain variable fragment (scFv) of the CAR may limit CAR‐T cell persistence and thus increases the risk of leukemia relapse. In this study, we developed a novel humanized scFv from the murine FMC63 antibody. A total of 18 R/R ALL patients with or without prior murine CD19 CAR‐T therapy were treated with humanized CD19‐targeted CAR‐T cells (hCART19s). After lymphodepletion chemotherapy with cyclophosphamide and fludarabine, the patients received a single dose (1 × 106/kg) of autologous hCART19s infusion. Among the 14 patients without previous CAR‐T therapy, 13 (92.9%) achieved complete remission (CR) or CR with incomplete count recovery (CRi) on day 30, whereas 1 of the 3 patients who failed a second murine CAR‐T infusion achieved CR after hCART19s infusion. At day 180, the overall and leukemia‐free survival rates were 65.8% and 71.4%, respectively. The cumulative incidence of relapse was 22.6%, and the nonrelapse mortality rate was 7.1%. During treatment, 13 patients developed grade 1‐2 cytokine release syndrome (CRS), 4 patients developed grade 3‐5 CRS, and 1 patient experienced reversible neurotoxicity. These results indicated that hCART19s could induce remission in patients with R/R B‐ALL, especially in patients who received a reinfusion of murine CAR‐T.
Evidence for additionally increased apoptosis in the peripheral blood mononuclear cells of major depressive patients with a high risk for suicide
Authors: Amidfar Meysam , Kim Yong‐Ku , Scaini Giselli , Quevedo João
Published: April 2018

Several studies have suggested a pathophysiological role of blood cell apoptosis in major depressive disorder (MDD). The aim of this study was to evaluate mRNA expression levels of Bcl‐2, Bax, and Fas in peripheral blood mononuclear cells (PBMCs) of MDD patients with a high risk for suicide relative to those without a high risk for suicide as well as healthy subjects. The mRNA expression of Bcl‐2, Bax, and Fas as well as the Bcl‐2/Bax ratio was examined in the PBMCs of 30 MDD patients with a high risk for suicide, 30 MDD patients without a high risk for suicide, and 30 healthy controls. The mRNA expression of target genes was measured using real‐time quantitative Polymerase Chain Reaction (PCR). FAS mRNA expression was significantly increased, and Bcl‐2 mRNA expression and the Bcl‐2/Bax expression ratio were significantly decreased, in the PBMCs of MDD patients with or without a high risk for suicide attempts compared to healthy controls (p < .001). However, Bax mRNA expression was significantly increased only in MDD patients with a high risk for suicide. Moreover, MDD patients with a high risk for suicide had increased Bax and FAS mRNA expression and decreased Bcl‐2 and Bcl‐2/Bax ratio when compared to patients without risk for suicide (p < .001). Our findings may support the role of both internal and external apoptotic pathways in the interplay between the immune system and depressive symptoms, especially in patients with a high risk for suicide.
A Radical Reaction for the Synthesis of 3‐Substituted Dihydrothiopyrans under Photosensitized Conditions
Authors: Fujiya Akitoshi , Yamaguchi Eiji , Tada Norihiro , Itoh Akichika
Published: April 2018

We report the synthesis of thiopyran derivatives under photosensitized conditions. This method is of interest for its reaction mechanism and is a novel synthetic route to heterocycles.
Practice Focus: The Duty of Candor, Inadvertent Production of Documents, and Your Arbitration Work
Authors: Barkett John M.
Published: April 2018

“The conduct of counsel in domestic arbitrations is subject to the rules of professional conduct for lawyers.”
Comparison of clinical practice guidelines for the management of pain, agitation, and delirium in critically ill adult patients
Authors: Tsuruta Ryosuke , Fujita Motoki
Published: April 2018

Guideline‐based management approaches for pain, agitation, and delirium (PAD) in critically ill adult patients are widely believed to result in good outcomes. However, there are some differences in the recommendations and evidence levels among the management guidelines established for PAD. To identify and compare the current management guidelines, we used the PubMed database. The PAD guidelines and Federación Panamericana e Ibérica de Sociedades de Medicina Crítica y Terapia Intensiva (FEPIMCTI) guidelines were identified from our search. We compared the main aspects of these two guidelines as well as the Japanese guidelines for the management of PAD (J‐PAD guidelines). The PAD, FEPIMCTI, and J‐PAD guidelines contained a total of 4, 12, and 5 sections, having 32, 138, and 37 recommendations, respectively, pertaining to routine monitoring of pain in adult patients in the intensive care unit. Intravenous opioids were recommended as the first‐line drug of choice for treating pain. Sedative titrated to maintain a light, rather than deep, level of sedation can be given unless clinically contraindicated. Although neither the PAD nor J‐PAD guidelines recommend use of a pharmacologic delirium prevention protocol or treatment with any pharmacological agent to reduce the duration of delirium, the FEPIMCTI guidelines provide such recommendations. The FEPIMCTI guidelines provide suggestions on which analgesics to use for several different cases and present algorithms for sedation and analgesia. The outlines of the three guidelines are similar, and all reinforce the management of PAD to improve patient outcomes.
Mild manifestation of methanol poisoning half a day after massive ingestion of a fuel alcohol product containing 70% ethanol and 30% methanol: a case report
Authors: Yoshizawa Tomohiro , Kamijo Yoshito , Fujita Yuji , Suzuki Yoshiki , Hanazawa Tomoki , Usui Kiyotaka , Kishino Tohru
Published: April 2018

Case

Is fomepizole necessary after massive ingestion of a mixture of methanol and ethanol? We report the case of a 37‐year‐old man who was transported to our Poison Center 12 h after ingesting 500 mL of fuel alcohol containing 70% methanol and 30% ethanol in a suicide attempt. On admission, he presented only with somnolence and mild metabolic acidosis. We hypothesized that most of the ethanol had been metabolized.

Outcome

As the estimated serum concentration of methanol was lethal (242.6 mg/dL), fomepizole was given i.v. and hemodialysis was carried out twice, resulting in complete recovery. Later, the serum concentrations of both methanol and ethanol on admission were found to be 224.1 and 0.51 mg/dL, respectively.

Conclusion

Therapeutic intervention was delayed by half a day after ingestion of a product containing methanol and ethanol in the present case. If the patient had arrived earlier, he may have only been treated with hemodialysis, but not fomepizole.
Ischemic stroke in cancer patients: A review of an underappreciated pathology
Authors: Navi Babak B. , Iadecola Costantino
Published: April 2018

Currently 1 in 10 patients with ischemic stroke have comorbid cancer, and this frequency is expected to increase with continued advances in cancer therapeutics prolonging median survival. Well known for its association with venous thrombosis, cancer has recently emerged as a significant risk factor for arterial thromboembolism, including stroke; however, the underlying mechanisms are uncertain. In addition, the optimal strategies to prevent and acutely treat stroke in cancer patients are yet to be established. This review summarizes the current evidence on ischemic stroke risk, biomarkers, pathophysiology, treatments, and prognosis in cancer patients, emphasizing knowledge gaps and the potential strategies to address them. Ann Neurol 2018;83:873–883
Crystal Adaptronics: Mechanically Reconfigurable Elastic and Superelastic Molecular Crystals
Authors: Ahmed Ejaz , Karothu Durga Prasad , Naumov Panče
Published: April 2018

Mechanically reconfigurable molecular crystals—ordered materials that can adapt to variable operating and environmental conditions by deformation, whereby they attain motility or perform work—are quickly shaping a new research direction in materials science, crystal adaptronics. Properties such as elasticity, superelasticity, and ferroelasticity, which are normally related to inorganic materials, and phenomena such as shape‐memory and self‐healing effects, which are well‐established for soft materials, are increasingly being reported for molecular crystals, yet their mechanism, quantification, and relation to the crystal structure of organic crystals are not immediately apparent. This Minireview provides a condensed topical overview of elastic, superelastic, and ferroelastic molecular crystals, new classes of materials that bridge the gap between soft matter and inorganic materials. The occurrence and detection of these unconventional properties, and the underlying structural features of the related molecular materials are discussed and highlighted with selected prominent recent examples.
Fused Isoindigo Ribbons with Absorption Bands Reaching Near‐Infrared
Authors: Jiang Yu , Zheng Xiaohua , Deng Yunfeng , Tian Hongkun , Ding Junqiao , Xie Zhigang , Geng Yanhou , Wang Fosong
Published: April 2018

Through fusing isoindigo (IID) units at 6,7;6′,7′‐positions, a series of new near‐infrared (NIR) absorbing and stable ribbon‐like conjugated molecules, namely nIIDs in which n represents the number of IID units, have been synthesized. The optical band gaps of the molecules are lowered from 2.03 eV of 1IID to 1.12 eV of 6IID with the increase of the conjugation length. 3IID, 4IID, and 6IID have strong absorption in the NIR region and exhibit photothermal conversion efficiencies of greater than 50 % under laser irradiation at λ=808 nm.
Fluorine‐Free Synthesis of High‐Purity Ti3C2Tx (T=OH, O) via Alkali Treatment
Authors: Li Tengfei , Yao Lulu , Liu Qinglei , Gu Jiajun , Luo Ruichun , Li Jinghan , Yan Xudong , Wang Weiqiang , Liu Pan , Chen Bin , Zhang Wang , Abbas Waseem , Naz Raheela , Zhang Di
Published: April 2018

MXenes, 2D compounds generated from layered bulk materials, have attracted significant attention in energy‐related fields. However, most syntheses involve HF, which is highly corrosive and harmful to lithium‐ion battery and supercapacitor performance. Here an alkali‐assisted hydrothermal method is used to prepare a MXene Ti3C2Tx (T=OH, O). This route is inspired from a Bayer process used in bauxite refining. The process is free of fluorine and yields multilayer Ti3C2Tx with ca. 92 wt % in purity (using 27.5 m NaOH, 270 °C). Without the F terminations, the resulting Ti3C2Tx film electrode (ca. 52 μm in thickness, ca. 1.63 g cm−3 in density) is 314 F g−1 via gravimetric capacitance at 2 mV s−1 in 1 m H2SO4. This surpasses (by ca. 214 %) that of the multilayer Ti3C2Tx prepared via HF treatments. This fluorine‐free method also provides an alkali‐etching strategy for exploring new MXenes for which the interlayer amphoteric/acidic atoms from the pristine MAX phase must be removed.
Selective Conversion of CO2 into Isocyanate by Low‐Coordinate Iron Complexes
Authors: Broere Daniël L. J. , Mercado Brandon Q. , Holland Patrick L.
Published: April 2018

Discovery of the mechanisms for selective transformations of CO2 into organic compounds is a challenge. Herein, we describe the reaction of low‐coordinate Fe silylamide complexes with CO2 to give trimethylsilyl isocyanate and the corresponding Fe siloxide complex. Kinetic studies show that this is a two‐stage reaction, and the presence of a single equivalent of THF influences the rates of both steps. Isolation of a thermally unstable intermediate provides mechanistic insight that explains both the effect of THF in this reaction, and the way in which the reaction achieves high selectivity for isocyanate formation.
CuI‐functionalized halloysite nanoclay as an efficient heterogeneous catalyst for promoting click reactions: Combination of experimental and computational chemistry
Authors: Bahri‐Laleh Naeimeh , Sadjadi Samaheh , Heravi Majid M. , Malmir Masoumeh
Published: April 2018

Amine‐functionalized halloysite nanotubes (HNTs‐2 N) were prepared and further modified by introduction of salicylaldehyde and formation of imine functionality (HNTs‐2 N‐Sal). The latter was subsequently used for immobilization of CuI and formation of CuI@HNTs‐2 N‐Sal, which could effectively promote click reactions of terminal alkynes, sodium azide and α‐haloketones or alkyl halides in aqueous media and under mild reaction conditions to afford 1,2,3‐triazoles in relatively short reaction times. Notably, the catalyst could be recycled in up to six reaction runs with negligible loss of catalytic activity and CuI leaching. Also, the geometry of CuI adsorption on the modified HNTs surface was explored by molecular simulation with density functional theory. Furthermore, topographic steric maps of possible coordination modes were obtained using the recently released SambVca2 web application tool. Based on obtained results, a catalytic site with superior performance was suggested.
A new Pd‐Schiff‐base complex on boehmite nanoparticles: Its application in Suzuki reaction and synthesis of tetrazoles
Authors: Jabbari Arida , Tahmasbi Bahman , Nikoorazm Mohsen , Ghorbani‐Choghamarani Arash
Published: April 2018

Boehmite nanoparticles are not air or moisture sensitive, therefore have been prepared in water without inert atmosphere using inexpensive materials. Pd‐isatin‐boehmite was synthesized and used as heterogeneous organometallic catalyst for the synthesis of 5‐substituted 1H‐tetrazoles and C‐C band formation. Pd‐isatin‐boehmite characterized by XRD, TGA, SEM and ICP‐OES techniques. This catalyst was reused for several times without significant loss of its catalytic efficiency or palladium leaching. Heterogeneity of this catalyst has been studied using ICP‐OES technique.
Degradation modeling of 2 fatigue‐crack growth characteristics based on inverse Gaussian processes: A case study
Authors: Rodríguez‐Picón Luis Alberto , Rodríguez‐Picón Anna Patricia , Alvarado‐Iniesta Alejandro
Published: April 2018

Most modern products that are highly reliable are complex in their inner and outer structures. This situation indicates quality characterization by the interaction of multiple performance characteristics, which motivates the utilization of robust reliability models to obtain robust estimates. It is paramount to obtaining substantial information about a product's life cycle; therefore, when multiple performance characteristics are dependent, it is important to find models that address the joint distribution of performance degradation of such. In this paper, a reliability model for products with 2 fatigue‐crack growth characteristics related to 2 degradation processes is developed. The proposed model considers the dependence among degradation processes by using copula functions considering the marginal degradation processes as inverse Gaussian processes. The statistical inference is performed by using a Bayesian approach to estimate the parameters of the joint bivariate model. A time‐scale transformation is considered to assure monotone paths of the degradation trajectories. The comparison results of the reliability analysis, under both dependent and independent assumptions, are reported with the implementation of the proposed modeling in a case study, which consists of the crack propagation data of 2 terminals of an electronic device.
Identification and characterization of a novel esterase from Thauera sp.
Authors: Yu Niu , Yang Jin‐chang , Yin Guang‐tian , Li Rong‐sheng , Zou Wen‐tao , He Chang
Published: April 2018

A novel esterase gene TLip was identified from the strain Thauera sp. and expressed at high levels in Escherichia coli. The TLip protein shared the highest identity (48%) to esterase TesA from Pseudomonas aeruginosa when compared to enzymes with reported properties. Phylogenetic analysis showed that TLip belongs to the GDSL family of bacterial lipolytic enzymes. TLip was an alkaline esterase with a broad optimal temperature range 37–50 °C and an optimal pH of 8.0. Substrate specificity assays showed that TLip preferred medium chain p‐nitrophenyl esters (C6–C12). Besides, the activity of TLip was strongly inhibited by Cu2+ but greatly enhanced by Triton X‐100 and Tween 80. Thermostability assay revealed that TLip was stable without loss of activity at 37 °C and still retained 69% activity at 50 °C after 2 H of incubation. Together, these provided a good candidate for further exploration of TLip as a promising biocatalyst in industry.
Effects of renal impairment on transporter‐mediated renal reabsorption of drugs and renal drug–drug interactions: A simulation‐based study
Authors: Follman Kristin E. , Dave Rutwij A. , Morris Marilyn E.
Published: April 2018

Renal impairment (RI) significantly impacts the clearance of drugs through changes in the glomerular filtration rate, protein binding and alterations in the expression of renal drug transport proteins and hepatic metabolizing enzymes. The objectives of this study were to evaluate quantitatively the effects of renal impairment on the pharmacokinetics of drugs undergoing renal transporter‐mediated reabsorption. A previously published semi‐mechanistic kidney model incorporating physiologically relevant fluid reabsorption and transporter‐mediated active renal reabsorption (PMID: 26341876) was utilized in this study. The probe drug/transporter pair utilized was γ‐hydroxybutyric acid (GHB) and monocarboxylate transporter 1 (SCL16A1, MCT1). γ‐Hydroxybutyric acid concentrations in the blood and amount excreted into urine were simulated using ADAPT 5 for the i.v. dose range of 200–1500 mg/kg in rats and the impact of renal impairment on CLR and AUC was evaluated. A 90% decrease in GFR resulted in a > 100‐fold decrease in GHB CLR. When expression of reabsorptive transporters was decreased and fu was increased, CLR approached GFR. The effect of renal impairment on CLR was reduced when the expression of drug metabolizing enzymes (DME) was increased as a result of increased metabolic clearance; the converse held true when the DME expression was decreased. In conclusion, this study quantitatively demonstrated that the effects of renal insufficiency on the clearance of drugs is modulated by transporter expression, contribution of renal clearance to overall clearance, expression of drug metabolizing enzymes, fraction unbound and drug–drug interactions with inhibitors of renal transporters that may be increased in the presence of renal impairment.
Switch rates do not influence weighting of rare events in decisions from experience, but optional stopping does
Authors: Soo Kevin W. , Rottman Benjamin M.
Published: April 2018

The current research investigates how people decide which of two options produces a better reward by repeatedly sampling from the options. In particular, it investigates the roles of two features of search, optional stopping and switch rate, on participants' final judgments of which option is better. First, in two studies, we found evidence for a new optional stopping effect; when participants stopped sampling right after experiencing a rare outcome, they made decisions as if they overweighted the rare outcome. Second, we investigated an effect proposed by Hills and Hertwig (2010) that people who frequently switch between options when sampling are more likely to make decisions consistent with underweighting rare outcomes. We conducted a theoretical analysis examining how switch rate can influence underweighting and how the type of decision problem moderates this effect. Informed by the theoretical analysis, we conducted four studies designed to test this effect with high power. None of the studies produced significant effects of switch rate. Lastly, the studies replicated a prior finding that optional stopping and switch rate are negatively correlated. In sum, this research elaborates a fuller understanding of the relation between search strategies (switch rate and optional stopping) on how people decide which option is better and their tendency to overweight versus underweight rare outcomes.
Gesundheit und Ernährung: Die Macht der Kultur
Authors: Hirschfelder Gunther
Published: April 2018

Trotz intensiver Aufklärung und weit verbreiteten Wissens zum Thema weist die Praxis der Ernährung in Deutschland heute bei vielen Konsumentengruppen in Bezug auf die Gesundheit großes Optimierungspotenzial auf. Das liegt zum einen an einer kognitiven Dissonanz: Dem Wissen um eine gesunde Ernährung steht eine der Gesundheit häufig nicht zuträgliche Praxis entgegen. Die Gründe hierfür sind vielfältig und werden in diesem Artikel zusammengefasst.
Besprechung mit Bananenquark
Authors: Hauk Andrea
Published: April 2018

Es wird viel diskutiert über die Vereinbarkeit von Familie und Beruf. Andrea Hauk – BIUZ‐Lesern bekannt als Autorin der Laborseite – hat den Praxistest gemacht und berichtet nun im achten Teil unserer Reihe von ihren Erfahrungen als Mutter eines Krabbelkindes, die wieder in den Beruf einsteigt.
Der Karpfen – Schmaus bei Festen und beim Fasten
Authors: Müller Thomas Volker
Published: April 2018

Der Karpfen (Cyprinus carpio) ist seit der Antike ein beliebter, weil schmackhafter und anspruchsloser Speisefisch. Er mag bevorzugt flaches, warmes Süßwasser und wird häufig in Fischteichen angezogen. In zahlreiche Länder weltweit wurde er eingeführt, wo er teilweise auch als invasive Art auftritt.