bluuebunny/crossref_metadata_2025 huggingface dataset:
Simultaneous Piezoelectrocatalytic Hydrogen‐Evolution and Degradation of Water Pollutants by Quartz Microrods@Few‐Layered MoS2 Hierarchical Heterostructures
Authors: Lin Yu‐Ting , Lai Sz‐Nian , Wu Jyh Ming
Published: July 2020

Intense light attenuation in water/wastewater results in photocatalysts exhibiting a low quantum efficiency. This study develops a novel piezoelectrocatalysis system, which involves quartz microrods (MRs) abundantly decorated with active‐edge‐site MoS2 nanosheets to form a quartz microrods@few‐layered MoS2 hierarchical heterostructure (QMSH). Through theoretical calculations, it is found that the quartz MRs serve as a parallel‐plate capacitor, which is self‐powered to provide an internal electric field to the few‐layered MoS2 nanosheets surrounding the quartz MR surfaces, and the piezoelectric potential (piezopotential) effectively facilitates redox reactions with the free carriers in MoS2. The self‐powered quartz MRs in the QMSH present an internal bias to the MoS2 nanosheets, thus yielding a piezoelectrocatalysis system. An efficient piezoelectrocatalytic hydrogen evolution reaction and decomposition of wastewater without light irradiation can be achieved simultaneously. The second‐order rate constant of the QMSH is ≈0.631 L mg−1 min−1, which is 650‐fold that of quartz MRs, indicating that the piezoelectric heterostructural catalysts display exceptionally high efficiency on piezoelectrocatalytic redox reactions rather than in the piezocatalytic process. The H2‐production rate of QMSH catalysts approaches ≈6456 µmo1 g−1 h−1 and peaks at ≈16.8 mmol g−1 in 8 h. The piezoelectrocatalytic process may be a promising method for treating industrial wastewater and producing clean energy.
An All‐Round Athlete on the Track of Phototheranostics: Subtly Regulating the Balance between Radiative and Nonradiative Decays for Multimodal Imaging‐Guided Synergistic Therapy
Authors: Zhang Zhijun , Xu Wenhan , Kang Miaomiao , Wen Haifei , Guo Heng , Zhang Pengfei , Xi Lei , Li Kai , Wang Lei , Wang Dong , Tang Ben Zhong
Published: July 2020

Aiming to achieve versatile phototheranostics with the integrated functionalities of multiple diagnostic imaging and synergistic therapy, the optimum use of dissipated energy through both radiative and nonradiative pathways is definitely appealing, yet a significantly challenging task. To the best of the knowledge, there have been no previous reports on a single molecular species effective at affording all phototheranostic modalities including fluorescence imaging (FLI), photoacoustic imaging (PAI), photothermal imaging (PTI), photodynamic therapy (PDT), and photothermal therapy (PTT). Herein, a simple and highly powerful one‐for‐all phototheranostics based on aggregation‐induced emission (AIE)‐active fluorophores is tactfully designed and constructed. Thanks to its strong electron donor–acceptor interaction and finely modulated intramolecular motion, the AIE fluorophore‐based nanoparticles simultaneously exhibit bright near‐infrared II (NIR‐II) fluorescence emission, efficient reactive oxygen species generation, and high photothermal conversion efficiency upon NIR irradiation, indicating the actualization of a balance between radiative and nonradiative energy dissipations. Furthermore, the unprecedented performance on NIR‐II FLI‐PAI‐PTI trimodal‐imaging‐guided PDT–PTT synergistic therapy is demonstrated by the precise tumor diagnosis and complete tumor elimination outcomes. This study thus brings a new insight into the development of superior versatile phototheranostics for practical cancer theranostics.
Galvanic Replacement of Liquid Metal/Reduced Graphene Oxide Frameworks
Authors: Wang Yushu , Wang Shengnan , Chang Hao , Rao Wei
Published: July 2020

Galvanic replacement reaction has been widely concerned, where a variety of materials can be nanostructured in different shapes. The galvanic replacement of gallium‐based liquid metals (LMs) can be remarkably valued, because the highly dynamic and homogeneous film of LMs can offer more active metal atoms for the reaction. Nevertheless, the galvanic replacement mechanism of the gallium‐based LM nanodroplets is still unrevealed entirely. To overcome this challenge, 2D graphene material (reduced graphene oxide, RGO) is employed to stabilize the liquid metal droplets and restrain the formation of oxide layer for the first time (LM@RGO). Two types of galvanic replacement patterns (intracellular and extracellular replacements) are revealed, which depend on the Gibbs free energy of redox reaction. The extracellular replacement pattern is adopted to produce the noble nanoparticles and the multilayered nanoparticles. In the intracellular replacement pattern, the galvanic replacement is not limited on the surface of LM@RGO. Owing to the internal alloying, LM@RGO with the superior electrochemical detection sensitivity is utilized to detect heavy metal ions. LM@RGO shows great potential in the application of preparing noble metal nanoparticles, the formation of composite nanoparticles with delicate structure and electrochemical detection of heavy metal ions.
Key Factor Study for Amphiphilic Block Copolymer‐Templated Mesoporous SnO2 Thin Film Synthesis: Influence of Solvent and Catalyst
Authors: Yin Shanshan , Tian Ting , Wienhold Kerstin S. , Weindl Christian L. , Guo Renjun , Schwartzkopf Matthias , Roth Stephan V. , Müller‐Buschbaum Peter
Published: July 2020

As a crucial material in the field of energy storage, SnO2 thin films are widely applied in daily life and have been in the focus of scientific research. Compared to the planar counterpart, mesoporous SnO2 thin films with high specific surface area possess more attractive physical and chemical properties. In the present work, a novel amphiphilic block copolymer‐assisted sol–gel chemistry is utilized for the synthesis of porous tin oxide (SnO2). Two key factors for the sol–gel stock solution preparation, the solvent category and the catalyst content, are systematically varied to tune the thin film morphologies. A calcination process is performed to remove the polymer template at 500 °C in ambient conditions. The surface morphology and the buried inner structure are probed with scanning electron microscope and grazing‐incidence small‐angle X‐ray scattering. Crystallinity is characterized by X‐ray diffraction. The multi‐dimensional characterization results suggest that cassiterite SnO2 with spherical, cylindrical, and vesicular pore structures are obtained. The variation of the film morphology is governed by the preferential affinity of the utilized solvent mixture and the hydrogen bond interaction between the employed cycloether and H2O molecules in the solution.
Nanoplatforms for mRNA Therapeutics
Authors: Meng Chaoyang , Chen Zhe , Li Gang , Welte Thomas , Shen Haifa
Published: July 2020

mRNA‐based therapeutics are a unique class of drugs for treatment of human diseases. Since in vitro transcribed mRNA molecules have relatively low stability and their surface charge prevents them from direct cell entry, they need to be packaged into specially designed delivery platforms to exert their activities. Multiple nanotechnology‐based delivery platforms have been developed for mRNA delivery, such as polymer‐based polyplex, lipid‐based lipoplex, and lipid‐coated polymer‐based lipopolyplex. In this review, an overview of the nanoplatforms for mRNA delivery is provided. A number of applications in biotechnology including cell reprogramming and gene editing are also described. In addition, their clinical translational potential for protein replacement therapy and for infectious disease and cancer treatment is introduced.
Sporopollenin Spikes Augment Antigen‐Specific Immune Response and Generate Long‐Lived Humoral Immunity
Authors: Uddin Md Jasim , Gonzalez‐Cruz Pedro , Warzywoda Juliusz , Gill Harvinder Singh
Published: July 2020

Oral vaccine delivery remains an unmet goal due to biochemical and immunological barriers in the gastrointestinal tract. Sporopollenin microcapsules from natural pollen grains have recently been engineered to overcome these multifaceted challenges. Using four morphologically different sporopollenin shells and two inbred mouse strains, this study addresses three key questions regarding sporopollenin shell's application for oral vaccine delivery: i) the impact of sporopollenin shell surface morphology on the immune response, ii) the duration of the immunity, and iii) the applicability of the delivery system across a diverse genetic background population. Using ovalbumin (OVA) as a model vaccine antigen, this study demonstrates that OVA can adsorb on the sporopollenin shell surfaces. Mice orally vaccinated with a sporopollenin shell‐based OVA formulation show sustained antibody responses for 454 days after the immunization that are correlated with the generation of OVA‐specific plasma cells in the vaccinated mice bone marrow. Sporopollenin shell surface spikes have a greater impact on immune responses than the shell size and shape. A spiky ragweed sporopollenin formulation induces systemic and mucosal responses in C57BL/6 and BALB/c mice. Together, this study provides a framework to select sporopollenin shells based on the surface morphology to use as a microcapsule for oral vaccination.
A Rotating Spiral Micromotor for Noninvasive Zygote Transfer
Authors: Schwarz Lukas , Karnaushenko Dmitriy D. , Hebenstreit Franziska , Naumann Ronald , Schmidt Oliver G. , Medina‐Sánchez Mariana
Published: July 2020

Embryo transfer (ET) is a decisive step in the in vitro fertilization process. In most cases, the embryo is transferred to the uterus after several days of in vitro culture. Although studies have identified the beneficial effects of ET on proper embryo development in the earlier stages, this strategy is compromised by the necessity to transfer early embryos (zygotes) back to the fallopian tube instead of the uterus, which requires a more invasive, laparoscopic procedure, termed zygote intrafallopian transfer (ZIFT). Magnetic micromotors offer the possibility to mitigate such surgical interventions, as they have the potential to transport and deliver cellular cargo such as zygotes through the uterus and fallopian tube noninvasively, actuated by an externally applied rotating magnetic field. This study presents the capture, transport, and release of bovine and murine zygotes using two types of magnetic micropropellers, helix and spiral. Although helices represent an established micromotor architecture, spirals surpass them in terms of motion performance and with their ability to reliably capture and secure the cargo during both motion and transfer between different environments. Herein, this is demonstrated with murine oocytes/zygotes as the cargo; this is the first step toward the application of noninvasive, magnetic micromotor‐assisted ZIFT.
Universal Memory Characteristics and Degradation Features of ZrO2‐Based Bipolar Resistive Memory
Authors: Hur Ji‐Hyun , Lee Dongsoo
Published: July 2020

A bilayer structured ZrO2‐based bipolar resistance random access memory (ReRAM) is demonstrated with near‐universal memory performances that meets almost all the requirements of the representative volatile and nonvolatile memories such as dynamic random access memory (DRAM) and NAND flash memory. The near‐universal device features include the very high initial on/off ratio up to 106, large switching endurance (1012 switching cycles), long retention (≈10 years), and fast programming speed (≈50 ns) along with the relatively small power consumption (≈50 pJ bit−1). Such high levels of performance and reliability characteristics of ReRAM are accomplished by adopting the layer‐by‐layer oxidation method that makes the junction of two oxide layers, ZrO2/TaOx, as sharp as possible. However, despite all these excellent features of the ReRAM, there are unwanted clear degradations of off‐state resistance as time and switching cycles go on in reliability tests resulting in a gradual decrease of the on/off ratio. Through theoretical simulations based on the self‐consistent switching model of bilayer oxide ReRAM, the underlying fundamental principles of this phenomenon are suggested, the validity of which are confirmed by excellent agreement with experiment.
Levers for Change and Unexpected Outcomes of a Participatory Research Partnership: Toward Fostering Older adults’ Social Participation to Promote Health Equity
Authors: Turcotte Pier‐Luc , Carrier Annie , Levasseur Mélanie
Published: July 2020

Promoting health equity in aging requires ensuring older adults’ effective access to community‐based services fostering their social participation. This study aimed to (a) identify levers for change in community‐based services to foster older adults’ social participation and (b) explore unexpected outcomes of stakeholder engagement. Based in a large Canadian city, a critical participatory research partnership was formed in a district experiencing considerable health disparities. Four focus groups and seven individual interviews were followed by a collaborative workshop with 28 community stakeholders. Participants identified mainly systemic and organizational levers for change. These levers comprised changing performance indicators and the institutional culture of homecare to value services fostering social participation opportunities. Other levers included supporting individual change agency through participatory research involving community members. Stakeholder engagement led to five unexpected outcomes: “Marking a new beginning,” “Expressing ourselves,” “Feeling better,” “Working together,” and “Influencing the community.” Recognizing levers for change is essential to understand how to develop services fostering social participation to promote health equity, with whom and in which contexts.
The CYB5R3c.350C>G and G6PD A alleles modify severity of anemia in malaria and sickle cell disease
Authors: Gordeuk Victor R. , Shah Binal N. , Zhang Xu , Thuma Philip E. , Zulu Stenford , Moono Rodgers , Reading N. Scott , Song Jihyun , Zhang Yingze , Nouraie Mehdi , Campbell Andrew , Minniti Caterina P. , Rana Sohail R. , Darbari Deepika S. , Kato Gregory J. , Niu Mei , Castro Oswaldo L. , Machado Roberto , Gladwin Mark T. , Prchal Josef T.
Published: July 2020

Genetic modifiers of anemia in Plasmodium falciparum infection and sickle cell disease (SCD) are not fully known. Both conditions are associated with oxidative stress, hemolysis and anemia. The CYB5R3 gene encodes cytochrome b5 reductase 3, which converts methemoglobin to hemoglobin through oxidation of NADH. CYB5R3c.350C > G encoding CYB5R3T117S, the most frequent recognized African‐specific polymorphism, does not have known functional significance, but its high allele frequency (23% in African Americans) suggests a selection advantage. Glucose‐6‐phosphate dehydrogenase (G6PD) is essential for protection from oxidants; its African‐polymorphic X‐linked A+ and A‐ alleles, and other variants with reduced activity, coincide with endemic malaria distribution, suggesting protection from lethal infection. We examined the association of CYB5R3c.350C > G with severe anemia (hemoglobin <5 g/dL) in the context of G6PD A+ and A‐ status among 165 Zambian children with malaria. CYB5R3c.350C > G offered protection against severe malarial anemia in children without G6PD deficiency (G6PD wild type or A+/A‐ heterozygotes) (odds ratio 0.29, P = .022) but not in G6PD A+ or A‐ hemizygotes/homozygotes. We also examined the relationship of CYB5R3c.350C > G with hemoglobin concentration among 267 children and 321 adults and adolescents with SCD in the US and UK and found higher hemoglobin in SCD patients without G6PD deficiency (β = 0.29, P = .022 children; β = 0.33, P = .004 adults). Functional studies in SCD erythrocytes revealed mildly lower activity of native CYB5R3T117S compared to wildtype CYB5R3 and higher NADH/NAD+ ratios. In conclusion, CYB5R3c.350C > G appears to ameliorate anemia severity in malaria and SCD patients without G6PD deficiency, possibly accounting for CYB5R3c.350C > G selection and its high prevalence.
Divergent Total Synthesis of Euphoranginol C, Euphoranginone D, ent‐Trachyloban‐3β‐ol, ent‐Trachyloban‐3‐one, Excoecarin E, and ent‐16α‐Hydroxy‐atisane‐3‐one
Authors: Xu Ze‐Jun , Zong Yan , Qiao Ya‐Nan , Zhang Jiao‐Zhen , Liu Xuyuan , Zhu Ming‐Zhu , Xu Yuliang , Zheng Hongbo , Fang Liyuan , Wang Xiao‐ning , Lou Hong‐Xiang
Published: July 2020

A divergent synthetic approach to biogenetically related diterpenoids such as ent‐kauranes, ent‐trachylobanes, ent‐beyerane, and ent‐atisane has been developed. The unified synthetic route involves the De Mayo reaction to rapidly generate the bicyclo[3.2.1]‐octane moiety of ent‐kaurane. The key reactions also include bioinspired nucleophilic cyclopropanation generating the [3.2.1.02,7]‐tricyclic core of ent‐trachylobane and regioselective cyclopropane fragmentation furnishing ent‐beyerane and ent‐atisane through the nucleophilic attack and protonation of the cyclopropane ring. This strategy enables the asymmetric total syntheses of six diterpenoids from the commercially available geraniol.
Influence of bidentate phosphine ligands on the chemistry of [FeFe]‐hydrogenase model: insight into molecular structures and electrochemical characteristics
Authors: El‐khateeb Mohammad , Abul‐Futouh Hassan , Alshurafa Hadil , Görls Helmar , Weigand Wolfgang
Published: July 2020

Substitution of carbonyl ligands of the hydrogenase model complex [Fe2(μ‐SeCH2CH(Me)CH2Se‐μ)(CO)6] (A), by 1,1′‐bis (diphenylphosphino)ferrocene (dppf), 1,2‐bis (diphenylphosphino)benzene (dppbz) or 1,2‐bis (diphenylphosphino)acetylene (dppac) is investigated. It is found that the reaction product depends on the diphosphine used. In the case of dppf, the product is an intramolecular bridged disubstituted complex [Fe2{μ‐SeCH2CH(Me)CH2Se‐μ}(CO)4{μ,κ1,κ1(P,P)‐dppf}] (1), while the dppac‐reaction produces an intermolecular bridged tetra‐iron model [Fe2{μ‐SeCH2CH(Me)CH2Se‐μ}(CO)5]2{μ,κ1,κ1(P,P)‐dppac} (2). However, the dppbz‐reaction gives [Fe2{μ‐SeCH2CH(Me)CH2Se‐μ}(CO)4{κ2(P,P)‐dppbz}] (3) in which the dppbz ligand is bonded to one Fe atom in a chelated manner. The newly prepared complexes (1–3) have been characterized by elemental analysis, IR, 1H‐, 13C{H}‐, 31P{H}‐, 77Se{H}‐NMR spectroscopy and X‐ray structure determination. The electrochemical behavior of 2 and 3, in absence and presence of acid, is described by cyclic voltammetric measurements in CH2Cl2.
Design, synthesis, and biological evaluation of new pyrazoloquinazoline derivatives as dual COX‐2/5‐LOX inhibitors
Authors: Shaaban Mohamed A. , Kamal Aliaa M. , Faggal Samar I. , Farag Nahla A. , Aborehab Nora M. , Elsahar Ayman E. , Mohamed Khaled O.
Published: July 2020

A new series of pyrazoloquinazoline derivatives equipped with different chalcones was designed, synthesized, and identified through 1H nuclear magnetic resonance (NMR), 13C NMR, and infrared spectroscopic techniques. Our design strategy of the quinazolinone‐privileged scaffold as a new scaffold was based on merging pharmacophores previously reported to exhibit cyclooxygenase‐2 (COX‐2)/5‐lipoxygenase (5‐LOX) inhibitory activity. All the newly synthesized derivatives were biologically evaluated for COX and 5‐LOX inhibitory activity and COX‐2 selectivity, using celecoxib and zileuton as reference drugs, as they exhibited promising anti‐inflammatory activity. Compound 3j was found to be the most promising derivative, with IC50 values of 667 and 47 nM against COX‐1 and COX‐2, respectively, which are superior to that of celecoxib (IC50 value against COX‐2 = 95 nM), showing an SI of 14.2 that was much better than celecoxib. Compounds 3f and 3h exhibited COX‐1 inhibition, with IC50 values of 1,485 and 684 nM, respectively. The synthesized compounds showed a significant inhibitory activity against 5‐LOX, with IC50 values ranging from 0.6 to 4.3 µM, where compounds 3f and 3h were found to be the most potent derivatives, with IC50 values of 0.6 and 1.0 µM, respectively, in comparison with that of zileuton (IC50 = 0.8 µM). These promising derivatives, 3f, 3h, and 3j, were further investigated in vivo for anti‐inflammatory, gastric ulcerogenic effects, and prostaglandin production (PGE2) in rat serum. The molecular docking studies concerning the binding sites of COX‐2 and 5‐LOX revealed similar orientation, compared with reported inhibitors, which encouraged us to design new leads targeting COX‐2 and 5‐LOX as dual inhibitors, as a new avenue in anti‐inflammatory therapy.
DAS‐IICognitive Profiles Are Not Diagnostically Meaningful For Autism: AROCAnalysis
Authors: Clements Caitlin C. , Sparding Timea , Schultz Robert T. , Yerys Benjamin E. , Watkins Marley W.
Published: July 2020

Intelligence assessment is an integral part of a comprehensive autism evaluation. Many past studies have described a cognitive profile of autistic individuals characterized by higher nonverbal than verbal IQ scores. The diagnostic utility of this profile, however, remains unknown. We leveraged receiver operating characteristic methods to determine the sensitivity, specificity, and area under the curve (AUC) of three different IQ profiles in a large sample of children who have an autism spectrum disorder diagnosis (N= 1,228, Simons Simplex Collection) who completed the Differential Ability Scales—Second Edition (DAS‐II), School Age compared to the normative sample provided by the DAS‐II publisher (N= 2,200). The frequently discussed nonverbal > verbal IQ profile performed near chance at distinguishing ASD from normative individuals (AUC: 0.54, 95% CI [0.52–0.56]), and performed significantly worse for females than males (AUC: females: 0.46 [0.41–0.52]; males: 0.55 [0.53–0.58]). All cognitive profiles showed AUC < 0.56. We conclude that while significant differences between verbal and nonverbal IQ scores exist at the group level, these differences are small in an absolute sense and not meaningful at an individual level. We do not recommend using cognitive profiles to aid in autism diagnostic decision‐making.

Lay Summary

Some researchers and clinicians have reported an “autistic cognitive profile” of higher nonverbal intelligence than verbal intelligence. In an analysis of over 1,000 autistic children, we found that thegroup'saverage nonverbal intelligence is usually higher than their verbal intelligence. However, this pattern should not be used by clinicians to make anindividualdiagnosis of autism because our results show it is not helpful nor accurate.
Bayesian inference for quantiles of the log‐normal distribution
Authors: Gardini Aldo , Trivisano Carlo , Fabrizi Enrico
Published: July 2020

The log‐normal distribution is very popular for modeling positive right‐skewed data and represents a common distributional assumption in many environmental applications. Here we consider the estimation of quantiles of this distribution from a Bayesian perspective. We show that the prior on the variance of the log of the variable is relevant for the properties of the posterior distribution of quantiles. Popular choices for this prior, such as the inverse gamma, lead to posteriors without finite moments. We propose the generalized inverse Gaussian and show that a restriction on the choice of one of its parameters guarantees the existence of posterior moments up to a prespecified order. In small samples, a careful choice of the prior parameters leads to point and interval estimators of the quantiles with good frequentist properties, outperforming those currently suggested by the frequentist literature. Finally, two real examples from environmental monitoring and occupational health frameworks highlight the improvements of our methodology, especially in a small sample situation.
Highly sensitive spectrofluorimetric procedure for the assay of phenothiazine derivatives in the presence of their sulfoxide oxidized product
Authors: Omar Mahmoud A. , Mohamed Abdel‐Maaboud , Nagy Dalia M. , Salem Hesham , Abdelmageed Osama H.
Published: July 2020

A validated straightforward and sensitive spectrofluorimetric procedure was developed to assay trifluoperazine hydrochloride, promethazine hydrochloride, and perazine maleate. The procedure was dependent on oxidation of the investigated phenothiazines using a known excess of ammonium cerium sulfate as oxidizing agent and overseeing the fluorescence intensity of the resultant Ce3+ion as the product of this reaction at λcx= 254 nm. and λem= 355 nm. Various parameters controlling the reaction were investigated and optimized. Linear calibration graphs were found in the general concentration range 5–30 ng/ml with a general correlation coefficient range 0.9994–0.9995. Limits of detection were 0.97, 0.70 and 0.56 ng/ml, whereas limits of quantification were 3.24, 2.12 and 1.89 ng/ml for trifluoperazine hydrochloride, promethazine hydrochloride and perazine maleate, respectively. The procedure was implemented successfully for analyses of the cited drugs in their trade dosage preparations such as tablets and syrups. The effect of possible interference from common excipients and their sulfoxide oxidized product was studied and the procedure showed good recovery of the drugs under study in their available dosage preparations. The possible effect of structure variation of the studied drugs on the experimental conditions and sensitivity observed with each one was also discussed.
Forskolin Increases cAMP Levels and Enhances Recombinant Antibody Production in CHO Cell Cultures
Authors: Yoon Chansik , Kim Dongil , Lim Ju Hyeon , Lee Gyun Min
Published: July 2020

Cyclic adenosine monophosphate (cAMP) is a ubiquitous second messenger essential to many biological processes. Forskolin, a labdane diterpene, is widely used to increase cAMP levels in various cell types. When 5 µm of forskolin is added to recombinant Chinese hamster ovary (rCHO) cell cultures producing monoclonal antibody (mAb) (GSR cell line), it decreases specific growth rate (μ), but increases culture longevity and specific mAb productivity (qmAb). The beneficial effect of forskolin on culture longevity and qmAb outweighs its detrimental effect on μ, resulting in 1.5‐fold increase in the maximum mAb concentration (MMC) without an adverse effect on mAb quality attributes such as aggregation, charge variation, and galactosylation. Forskolin induces cell cycle arrest at the G0/G1 phase via the LKB1/AMPK pathway and inhibits apoptosis via the CREB/Bcl‐2 pathway. The beneficial effect of forskolin on mAb production is also demonstrated with another rCHO cell line (ABTAA). Addition of 5 µm forskolin to ABTAA cell cultures also results in 1.5‐fold increase in the MMC. Taken together, the results obtained demonstrate that forskolin is an efficient chemical reagent to increase mAb production in rCHO cell cultures.
Neutrophil‐to‐lymphocyte ratio, hyperglycemia, and outcomes in ischemic stroke patients treated with intravenous thrombolysis
Authors: Cheng Yani , Ying Anna , Lin Yanyan , Yu Junru , Luo Ji , Zeng Yifan , Lin Yuanshao
Published: July 2020

Introduction

Increased neutrophil‐to‐lymphocyte ratio (NLR) and hyperglycemia on admission are associated with poor outcomes in acute ischemic stroke (AIS) patients. We sought to evaluate the combined effect of increased NLR and hyperglycemia on the prognosis of ischemia stroke treated with intravenous thrombolysis (IVT).

Methods

Patients with acute ischemic stroke receiving IVT treatment were prospectively enrolled. All participants were followed for 3 months. According to the levels of NLR and blood glucose, patients were categorized into four groups: high NLR or nonhigh NLR with or without hyperglycemia. The associations between NLR values with or without hyperglycemia and outcomes of stroke after thrombolysis were assessed by multivariable logistic regression analysis.

Results

Among the 381 stroke patients (median age 68 years, 61.68% man) included, 155 (40.68%) had a poor outcome (modified Rankin Scale score 3–6) during 3 months. After multivariate adjustment, high NLR with hyperglycemia increased the risk of 3‐month poor outcome (OR = 4.42; 95% CI, 2.13–9.16), early neurological deterioration (END) (OR = 4.81; 95% CI, 2.08–11.12), and 3‐month mortality (OR = 6.56; 95% CI, 1.92–22.40). A significant multiplicative interaction of NLR and blood glucose on 3‐month poor outcome in ischemic stroke patients after thrombolysis was observed.

Conclusions

Ischemic stroke patients with concurrent high NLR and hyperglycemia increased risks of END, 3‐month poor outcome, and mortality after thrombolysis.
Total Synthesis and Structural Revision of Kasumigamide, and Identification of a New Analogue
Authors: Kuranaga Takefumi , Matsuda Kenichi , Takaoka Masachika , Tachikawa Chisato , Sano Ayae , Itoh Kosei , Enomoto Ayumu , Fujita Kei , Abe Ikuro , Wakimoto Toshiyuki
Published: July 2020

Kasumigamide is an antialgal hybrid peptide–polyketide isolated from the freshwater cyanobacterium Microcystis aeruginosa (NIES‐87). The biosynthetic gene cluster was identified from not only the cyanobacterium but also Candidatus “Entotheonella”, associated with the Japanese marine sponge Discodermia calyx. Therefore, kasumigamide is considered to play a key role in microbial ecology, regardless of the terrestrial and marine habitats. We now report synthetic studies on this intriguing natural product that have led to a structural revision and the first total synthesis. During this study, a new analogue, deoxykasumigamide, was also isolated and structurally validated. This study confirmed the presence of the unusual pathway in the biosynthesis of a hybrid peptide–polyketide natural product.
Active Bicomponent Nanoparticle Assembly with Temporal, Microstructural, and Functional Control
Authors: Dhiman Shikha , Singh Akanksha , George Subi J.
Published: July 2020

Transient supramolecular self‐assembly has evolved as a tool to create temporally programmable smart materials. Yet, so far single‐component self‐assembly has been mostly explored. In contrast, multicomponent self‐assembly provides an opportunity to create unique nanostructures exhibiting complex functional outcomes, newer and different than individual components. Even two‐component can result in multiple organizations, such as self‐sorted domains or co‐assembled heterostructures, can occur, thus making it highly complex to predict and reversibly modulate these microstructures. In this study, we attempted to create active bicomponent nanoparticle assemblies of orthogonally pH‐responsive‐group‐functionalized gold and cadmium selenide nanoparticles with temporal microstructural control on their composition (self‐sorted or co‐assembly) in order to harvest their emergent transient photocatalytic activity by coupling to temporal changes in pH. Moving towards multicomponent systems can deliver next level control in terms of structural and functional outcomes of supramolecular systems.
Sprunginnovationen
Authors: Böck Barbara
Published: July 2020

No abstract.
A quality‐adjusted survival time without symptoms or toxicities analysis of glasdegib plus low‐dose cytarabine versus low‐dose cytarabine as initial therapy for acute myeloid leukemia in patients who are not considered candidates for intensive chemotherapy
Authors: Solem Caitlyn T. , Bell Timothy J. , Kwon Youngmin , Cappelleri Joseph C. , Johnson Courtney , Bhattacharyya Helen , Hoang Caroline J. , Cortes Jorge E.
Published: July 2020

Background

In a randomized study, glasdegib (a hedgehog inhibitor) plus low‐dose cytarabine (LDAC) significantly prolonged survival in comparison with LDAC in patients with acute myeloid leukemia (AML). A quality‐adjusted time without symptoms of disease progression or toxicity (Q‐TWiST) approach was used to evaluate comparative quality‐adjusted survival.

Methods

Overall survival was partitioned into the following: time with any treatment‐emergent grade 3 or higher adverse events (TOX); time without symptoms of disease progression or toxicity (TWiST); and time after treatment discontinuation due to insufficient clinical response, relapse, or death time after progression (REL). Q‐TWiST was calculated by multiplying the restricted mean time in each state by respective utilities and then summing up the utility‐adjusted time.

Results

At 20 months of follow‐up, the survival probabilities for the glasdegib‐LDAC arm and the LDAC arm were 28.2% and 7.9%, respectively. Glasdegib‐LDAC patients (n = 78), in comparison with LDAC patients (n = 38), had significantly longer mean TWiST (+3.4 months; 95% confidence interval [CI], 1.8‐5.2 months) and TOX (+0.8 months; 95% CI, 0.1‐1.6 months) and longer but nonsignificant REL (+0.3 months; 95% CI, −1.9 to 2.3 months). Q‐TWiST was 4.0 months (95% CI, 2.1‐5.8 months) longer with glasdegib plus LDAC, and this translated into a 75% relative improvement in quality‐adjusted survival with respect to LDAC. Results were robust to the length of follow‐up (6‐24 months) and remained significant when all adverse events, regardless of grade, were included.

Conclusions

These results suggest that most of the survival benefit from glasdegib plus LDAC versus LDAC alone is TWiST, and this represents added time in relatively “good” health. These results support the clinical value of glasdegib plus LDAC as initial therapy for AML in patients for whom intensive chemotherapy is not an option.
Clinical benefit and cost of breakthrough cancer drugs approved by the US Food and Drug Administration
Authors: Molto Consolación , Hwang Thomas J. , Borrell Maria , Andres Marta , Gich Ignasi , Barnadas Agustí , Amir Eitan , Kesselheim Aaron S. , Tibau Ariadna
Published: July 2020

Background

The clinical benefit and pricing of breakthrough‐designated cancer drugs are uncertain. This study compares the magnitude of the clinical benefit and monthly price of new and supplemental breakthrough‐designated and non–breakthrough‐designated cancer drug approvals.

Methods

A cross‐sectional cohort comprised approvals of cancer drugs for solid tumors from July 2012 to December 2017. For each indication, the clinical benefit from the pivotal trials was scored via validated frameworks: the American Society of Clinical Oncology Value Framework (ASCO‐VF), the American Society of Clinical Oncology Cancer Research Committee (ASCO‐CRC), the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO‐MCBS), and the National Comprehensive Cancer Network (NCCN) Evidence Blocks. A high clinical benefit was defined as scores ≥ 45 for the ASCO‐VF, overall survival gains ≥ 2.5 months or progression‐free survival gains ≥ 3 months for all cancer types for the ASCO‐CRC criteria, a grade of A or B for trials of curative intent and a grade of 4 or 5 for trials of noncurative intent for the ESMO‐MCBS, and scores of 4 and 5 and a combined score ≥ 16 for the NCCN Evidence Blocks. Monthly Medicare drug prices were calculated with Medicare prices and DrugAbacus.

Results

This study identified 106 trials supporting approval of 52 drugs for 96 indications. Forty percent of these indications received the breakthrough designation. Among the included trials, 33 (43%), 46 (73%), 35 (34%), and 67 (69%) met the thresholds established by the ASCO‐VF, ASCO‐CRC, ESMO‐MCBS, and NCCN, respectively. In the metastatic setting, there were higher odds of clinically meaningful grades in trials supporting breakthrough drugs with the ASCO‐VF (odds ratio [OR], 3.69; P = .022) and the NCCN Evidence Blocks (OR, 5.80; P = .003) but not with the ASCO‐CRC (OR, 3.54; P = .11) or version 1.1 (v1.1) of the ESMO‐MCBS (OR, 1.22; P = .70). The median costs of breakthrough therapy drugs were significantly higher than those of nonbreakthrough therapies (P = .001).

Conclusions

In advanced solid cancers, drugs that received the breakthrough therapy designation were more likely than nonbreakthrough therapy drugs to be scored as providing a high clinical benefit with the ASCO‐VF and the NCCN Evidence Blocks but not with the ESMO‐MCBS v1.1 or the ASCO‐CRC scale.
Risk of invasive prostate cancer and prostate cancer death in relatives of patients with prostatic borderline or in situ neoplasia: A nationwide cohort study
Authors: Xu Xing , Fallah Mahdi , Tian Yu , Mukama Trasias , Sundquist Kristina , Sundquist Jan , Brenner Hermann , Kharazmi Elham
Published: July 2020

Background

The question of whether having a family history of prostatic borderline or in situ neoplasia (PBISN) is associated with an increased risk of invasive prostate cancer (PCa) or death from PCa remains unanswered. The objective of the current study was to provide an evidence‐based risk estimation for the relatives of patients with PBISN.

Methods

Nationwide Swedish family cancer data sets were used for the current study, including data regarding all residents of Sweden who were born after 1931 and their parents. Standardized incidence ratios (SIRs), standardized mortality ratios (SMRs), and lifetime cumulative risks of PCa were calculated for men with different constellations of family history. Family history was defined as a dynamic (time‐dependent) variable considering changes during follow‐up (1958‐2015).

Results

Of the 6,343,727 men in the current study, a total of 238,961 developed invasive PCa and 5756 were diagnosed with PBISN during the follow‐up. Men with 1 first‐degree relative who was diagnosed with PBISN had a 70% increased risk of invasive PCa (SIR, 1.7; 95% confidence interval, 1.5‐1.9) and PCa death (SMR, 1.7; 95% confidence interval, 1.3‐2.2) compared with men with no family history of PBISN or invasive PCa. These were rather close to estimates in men with 1 first‐degree relative diagnosed with invasive PCa (SIR, 2.1 and SMR, 1.8). A higher risk of PCa in family members was found among patients with a family history of PBISN and/or PCa diagnosed before age 60 years. The results in terms of cumulative risk resembled this trend.

Conclusions

A family history of PBISN appears to be as important as a family history of invasive PCa with regard to an increased risk of invasive PCa or PCa mortality. Such a history should not be overlooked in PCa screening recommendations or in future research regarding familial PCa.
Social recommendation algorithms with user feedback information
Authors: Yu Yuecheng , Gu Yu , Zuo Huayu , Wang Jinlei , Wang Dongsheng
Published: July 2020

Social media information can effectively improve the performance of personalized recommendation model. However, the feedback information in the social media which can accurately reflect users' implicit preferences is often ignored by most existing methods. To improve the users' experience and reduce the push of unwelcome information, in this article, we propose a new social recommendation algorithm with user feedback information. Different from the existing recommendation methods based on probability matrix decomposition, we incorporate the user implicit feedback information into the user rating prediction function. To reduce the data sparsity of implicit feedback information, we also adopt social network trust calculation in our algorithm. As a result, we can not only optimize the recommendation list but also filter out most of disgusting content. Compared with PMF, UserCF, CUNE, and TrustSVD, but slightly lower than RSTE, the experimental results of our model on real‐world datasets demonstrate the effectiveness of our proposed method, and further verify that the user experience is significantly improved without obviously reducing the accuracy of the recommendation.
A machine learning‐based memory forensics methodology for TOR browser artifacts
Authors: Pizzolante Raffaele , Castiglione Arcangelo , Carpentieri Bruno , Contaldo Roberto , D'Angelo Gianni , Palmieri Francesco
Published: July 2020

At present, 96% of the resources available into the World‐Wide‐Web belongs to the Deep Web, which is composed of contents that are not indexed by search engines. The Dark Web is a subset of the Deep Web, which is currently the favorite place for hiding illegal markets and contents. The most important tool that can be used to access the Dark Web is the Tor Browser. In this article, we propose a bottom‐up formal investigation methodology for the Tor Browser's memory forensics. Based on a bottom‐up logical approach, our methodology enables us to obtain information according to a level of abstraction that is gradually higher, to characterize semantically relevant actions carried out by the Tor browser. Again, we show how the proposed three‐layer methodology can be realized through open‐source tools. Also, we show how the extracted information can be used as input to a novel Artificial Intelligence‐based architecture for mining effective signatures capable of representing malicious activities in the Tor network. Finally, to assess the effectiveness of the proposed methodology, we defined three test cases that simulate widespread real‐life scenarios and discuss the obtained results. To the best of our knowledge, this is the first work that deals with the forensic analysis of the Tor Browser in a live system, in a formal and structured way.
Rainbow: A composable coherence protocol for multi‐chip servers
Authors: Menezo Lucia G. , Puente Valentin , Gregorio Jose A
Published: July 2020

The use of multi‐chip modules (MCM) and/or multi‐socket boards is the most suitable approach to increase the computation density of servers while keep chip yield attained. This article introduces a new coherence protocol suitable, in terms of complexity and scalability, for this class of systems. The proposal uses two complementary ideas: (1) A mechanism that dissociates complexity from performance by means of colored‐token counting, (2) A construct that optimizes performance and cost by means of two functionally symmetrical structures working in the last level cache of each chip and each memory controller. The coordinated work of both structures minimizes the coherence‐related effects on the average memory latency perceived by the processor. Our proposal is able to improve on the performance of a HyperTransport‐like coherence protocol by from 25% to 60%.
X‐Ray Topography—More than Nice Pictures
Authors: Danilewsky Andreas N.
Published: July 2020

X‐ray topography—a well‐known diffraction imaging method—is widely used for the characterization of extended crystal defects like dislocations. Herein, the progress toward the quantification besides the number and nature of dislocations is given. The diffracted images include additional information about tilt and strain, which can be measured in real‐time, thanks to the improved digital detection systems. This allows not only the fast mapping of huge samples like 450 mm diameter Si wafers, the in situ observation of the dislocation, or crack dynamics at high temperatures, but also the stress analysis in electronic devices in operando. In addition to typical white X‐ray beam methods like stacks of section topographs, the monochromatic diffraction laminography allows a 3D representation of the dislocation arrays. The merits and limitations of X‐ray topography are demonstrated by semiconductor materials as an example.
Interspecific comparisons of C3turfgrass for tennis use: II. Investigation of ball friction, ball bounce, and associated factors in replicated grass courts
Authors: Ebdon J. S. , James I. , DaCosta M. , Lu J.
Published: July 2020

Tennis is played on many different surfaces including natural grass, which plays fast because of low ball bounce (i.e., coefficient of restitution [COR]) and low ball‐to‐surface friction (coefficient of friction [COF]) that increase the pace (ball speed) of tennis. Effects of various C3turfgrasses on COF and COR have not been investigated. Our objectives were to evaluate eight cultivars of various species randomized within three official size tennis courts: (a) ‘Keeneland’ Kentucky bluegrass (Poa pratensisL., KB), (b) ‘Rubix’ KB, (c) ‘Villa’ velvet bentgrass (Agrostis caninaL., VBG), (d) ‘Puritan’ colonial bentgrass (Agrostis capillarisL., CL), (e) ‘007’ creeping bentgrass (Agrostis stoloniferaL., CB), (f) fine fescue (Festucasp., FF) mixture, (g) ‘Karma’ perennial ryegrass (Lolium perenneL, PR), and (h) ‘Wicked’ PR. Friction was measured using a weighted sled and ball bounce (BB) to derive COR was measured using a vertical drop height of 254 cm. Bounce (i.e., COR) to satisfy the International Tennis Federation (ITF) minimum of 50% BB (COR = 0.70) was not observed on any of the species evaluated. Species such as FF and PR were able to achieve BB to satisfy the ITF 80% BB minimum to that observed on smooth concrete. Linear regression indicated that 170gof surface hardness for FF and PR to as much as 200gon KB and higher on BG may be needed to achieve a COR = 0.70. Hemi‐ and lignocellulose cell wall fractions were correlated with COR and COF but exhibited significant and opposite relationships. Achieving higher COF may be a more practical means to slow court pace of notoriously fast grass courts. Future research will be needed to investigate the effects of cultural practices on COF.
Sustainable Strategies in the Synthesis of Lignin Nanoparticles for the Release of Active Compounds: A Comparison
Authors: Cailotto Simone , Gigli Matteo , Bonini Massimo , Rigoni Federica , Crestini Claudia
Published: July 2020

The preparation of nanoparticles represents a powerful tool for lignin valorization, as it combines easy methodologies with high application potential. Different synthetic strategies and various lignin sources have been employed in the process. However, the great variability in the lignin structure prevents a direct comparison of the so far reported lignin nanoparticles (LNPs), especially as regards their physicochemical and functional properties. To this purpose, two green protocols, that is, solvent‐antisolvent and hydrotropic, were optimized and used to generate LNPs from the same softwood kraft lignin. The nanomaterials were fully characterized to extrapolate structure/property relationships and reveal any differences in the mechanism of self‐assembly. Furthermore, tests on methylene blue entrapment capacity and release behavior at two different pH values (2.0 and 7.4) evidenced a clear dependence on the LNPs characteristics and thus on the strategy adopted for their production.
Interface Engineering of Binder‐Free Earth‐Abundant Electrocatalysts for Efficient Advanced Energy Conversion
Authors: Wang Peican , Wang Baoguo
Published: July 2020

Gas‐involved electrocatalysts for the hydrogen evolution reaction, oxygen evolution reaction, and oxygen reduction reaction are crucial for many clean and effective energy technologies. The interface chemistry of electrocatalysts plays an important role in the optimization of their catalytic activity and stability. However, these gas‐involved reactions exhibit sluggish kinetics and complex reactions at triple‐phase interfaces. Thus, interface engineering at multiscale levels plays a decisive role. Binder‐free electrocatalysts have gained increasing popularity, owing to their enhanced electron transfer and improved mass diffusion. This Review summarizes the influence of binder‐free electrocatalysts with optimized interfaces and emphasizes three key interfaces, including the electrocatalyst/substrate interface, the inner interface of the electrocatalyst, and the electrocatalyst/electrolyte/gas interface, which are integral to determining the properties of gas‐involved electrocatalysts, including the electrical conductivity, intrinsic catalytic activity, and mass transfer behavior. Finally, prospects and future challenges for the further development of binder‐free electrocatalysts are discussed.