bluuebunny/crossref_metadata_2025 huggingface dataset:
Drivers of Satisfaction With Care for Patients With Lupus
Authors: Jolly Meenakshi , Sethi Bhavika , O'Brien Courtney , Sequeira Winston , Block Joel A. , Toloza Sergio , Bertoli Ana , Blazevic Ivana , Vilá Luis M. , Moldovan Ioana , Torralba Karina D. , Cicognani Elvira , Mazzoni Davide , Hasni Sarfaraz , Goker Berna , Haznedaroglu Seminur , Bourre‐Tessier Josiane , Navarra Sandra V. , Mok Chi Chiu , Clarke Ann , Weisman Michael , Wallace Daniel
Published: November 2019

Objective

Quality of life (QOL) and quality of care (QOC) in systemic lupus erythematosus (SLE) remains poor. Satisfaction with care (SC), a QOC surrogate, correlates with health behaviors and outcomes. This study aimed to determine correlates of SC in SLE.

Methods

A total of 1262 patients with SLE were recruited from various countries. Demographics, disease activity (modified Systemic Lupus Erythematosus Disease Activity Index for the Safety of Estrogens in Lupus Erythematosus: National Assessment trial [SELENA‐SLEDAI]), and QOL (LupusPRO version 1.7) were collected. SC was collected using LupusPRO version 1.7. Regression analyses were conducted using demographic, disease (duration, disease activity, damage, and medications), geographic (eg, China vs United States), and QOL factors as independent predictors.

Results

The mean (SD) age was 41.7 (13.5) years; 93% of patients were women. On the univariate analysis, age, ethnicity, current steroid use, disease activity, and QOL (social support, coping) were associated with SC. On the multivariate analysis, Asian participants had worse SC, whereas African American and Hispanic patients had better SC. Greater disease activity, better coping, and social support remained independent correlates of better SC. Compared with US patients, patients from China and Canada had worse SC on the univariate analysis. In the multivariate models, Asian ethnicity remained independently associated with worse SC, even after we adjusted for geographic background (China). No associations between African American or Hispanic ethnicity and SC were retained when geographic location (Canada) was added to the multivariate model. Canadian patients had worse SC when compared with US patients. Higher disease activity, better social support, and coping remained associated with better SC.

Conclusion

Greater social support, coping, and, paradoxically, SLE disease activity are associated with better SC. Social support and coping are modifiable factors that should be addressed by the provider, especially in the Asian population. Therefore, evaluation of a patient's external and internal resources using a biopsychosocial model is recommended. Higher disease activity correlated with better SC, suggesting that the latter may not be a good surrogate for QOC or health outcomes.
Neural network–based direct adaptive robust control of unknown MIMO nonlinear systems using state observer
Authors: Cheng Cheng , Liu Songyong , Wu Hongzhuang , Zhang Ying
Published: November 2019

This paper focuses on the problem of adaptive robust tracking control for a class of uncertain multiple‐input and multiple‐output (MIMO) nonlinear system. Unlike most previous research studies, model dynamics, disturbances, and state variables are unknown in this paper. A novel observer‐based direct adaptive neuro‐sliding mode control approach is proposed of which the only required knowledge is the system output. By incorporating the Adaptive Linear Neuron (ADALINE) neural network (NN) into the conventional sliding mode observer, the proposed observer has favorable performance. In the controller, a radial basis function (RBF) NN is constructed to approximate the unknown equivalent control laws and the estimation of the sliding surface is applied as the input. A gain‐adaptation sliding mode term is designed to enhance the robustness of the control system. Besides, the free parameters of the ADALINE NN and the RBFNN are updated online by adaptive laws to obtain optimal approximation performance. Finally, the comparative simulations are given to show the effectiveness and merits of proposed scheme.
Elevated Temperature Compression Deformation Behavior of Commercial Pure Zr Combined with the Constitutive Equation and Processing Map
Authors: Wang Qingjuan , Li Xiangjun , Wang Kuaishe , Zhang Bing , Cai Jun , Tong Libo , Ren Yaojia , Zeng Zhouyu , Dang Jun
Published: November 2019

The compression deformation behavior of commercial pure zirconium at elevated temperature is systematically investigated at different conditions. The corresponding deformation mechanism of pure Zr is clarified for analyzed flow stress, work hardening rate, activation energy, and microstructure. A modified Arrhenius‐type equation is proposed for future numerical simulation, which shows a good relativity between the theoretical and experimental data. The apparent deformation activation energy is 209 kJ mol−1, indicating that a cross‐slip of dominant dislocation mechanism controls the deformation process. Established based on the dynamic material model (DDM), processing maps indicate that the optimum processing conditions are 700–900 °C at 0.1–0.14 s−1 and 905–950 °C at 3–20 s−1 with the high efficiency of power dissipation. Microstructure examination reveals that the main restoration mechanism in the safe domain is related to dynamic recrystallization and the unstable regional microstructure results in the flow localization and cracking behavior.
Intra/Extracellular Lactic Acid Exhaustion for Synergistic Metabolic Therapy and Immunotherapy of Tumors
Authors: Gao Fan , Tang Ying , Liu Wen‐Long , Zou Mei‐Zhen , Huang Cui , Liu Chuan‐Jun , Zhang Xian‐Zheng
Published: November 2019

Regulating the tumor microenvironment (TME) has been a promising strategy to improve antitumor therapy. Here, a red blood cell membrane (mRBC)‐camouflaged hollow MnO2 (HMnO2) catalytic nanosystem embedded with lactate oxidase (LOX) and a glycolysis inhibitor (denoted as PMLR) is constructed for intra/extracellular lactic acid exhaustion as well as synergistic metabolic therapy and immunotherapy of tumor. Benefiting from the long‐circulation property of the mRBC, the nanosystem can gradually accumulate in a tumor site through the enhanced permeability and retention (EPR) effect. The extracellular nanosystem consumes lactic acid in the TME by catalyzing its oxidation reaction via LOX. Meanwhile, the intracellular nanosystem releases the glycolysis inhibitor to cut off the source of lactic acid, as well as achieve antitumor metabolic therapy through the blockade of the adenosine triphosphate (ATP) supply. Both the extracellular and intracellular processes can be sensitized by O2, which can be produced during the decomposition of endogenous H2O2 catalyzed by the PMLR nanosystem. The results show that the PMLR nanosystem can ceaselessly remove lactic acid, and then lead to an immunocompetent TME. Moreover, this TME regulation strategy can effectively improve the antitumor effect of anti‐PDL1 therapy without the employment of any immune agonists to avoid the autoimmunity.
Interfacial Lattice‐Strain‐Driven Generation of Oxygen Vacancies in an Aerobic‐Annealed TiO2(B) Electrode
Authors: Zhang Wei , Cai Lingfeng , Cao Shengkai , Qiao Liang , Zeng Yi , Zhu Zhiqiang , Lv Zhisheng , Xia Huarong , Zhong Lixiang , Zhang Hongwei , Ge Xiang , Wei Jiaqi , Xi Shibo , Du Yonghua , Li Shuzhou , Chen Xiaodong
Published: November 2019

Oxygen vacancies play crucial roles in defining physical and chemical properties of materials to enhance the performances in electronics, solar cells, catalysis, sensors, and energy conversion and storage. Conventional approaches to incorporate oxygen defects mainly rely on reducing the oxygen partial pressure for the removal of product to change the equilibrium position. However, directly affecting reactants to shift the reaction toward generating oxygen vacancies is lacking and to fill this blank in synthetic methodology is very challenging. Here, a strategy is demonstrated to create oxygen vacancies through making the reaction energetically more favorable via applying interfacial strain on reactants by coating, using TiO2(B) as a model system. Geometrical phase analysis and density functional theory simulations verify that the formation energy of oxygen vacancies is largely decreased under external strain. Benefiting from these, the obtained oxygen‐deficient TiO2(B) exhibits impressively high level of capacitive charge storage, e.g., ≈53% at 0.5 mV s−1, far surpassing the ≈31% of the unmodified counterpart. Meanwhile, the modified electrode shows significantly enhanced rate capability delivering a capacity of 112 mAh g−1 at 20 C (≈6.7 A g−1), ≈30% higher than air‐annealed TiO2 and comparable to vacuum‐calcined TiO2. This work heralds a new paradigm of mechanical manipulation of materials through interfacial control for rational defect engineering.
3D Printing of Compositional Gradients Using the Microfluidic Circuit Analogy
Authors: Nguyen Du T. , Yee Timothy D. , Dudukovic Nikola A. , Sasan Koroush , Jaycox Adam W. , Golobic Alexandra M. , Duoss Eric B. , Dylla‐Spears Rebecca
Published: November 2019

3D printing of structures with compositional gradients requires accurate dispensing control to achieve desired profiles. Here, empirical data are used with a model based on the microfluidic circuit analogy (MCA) to project dispense rate profiles that yield improved compositional accuracy in the printed part. Since minor variation in the experimental setup for each printing session can result in significant changes, a calibration procedure is developed to measure the system response. This calibration enables the extraction of the empirical MCA model parameters specific to each print session. Using the empirical parameters, the MCA model then can be used to predict appropriate dispense rates for the desired composition profile and toolpath of interest. The MCA model is validated experimentally by direct ink write 3D printing of compositional gradients using viscoelastic polydimethylsiloxane inks and is shown to improve accuracy to desired profile by a factor of 2–5. This approach enables a new route to 3D print structures with arbitrarily complex compositional gradients.
Adhesion‐Engineering‐Enabled “Sketch and Peel” Lithography for Aluminum Plasmonic Nanogaps
Authors: Chen Yiqin , Zhang Shi , Shu Zhiwen , Wang Zhaolong , Liu Peng , Zhang Chen , Wang Yasi , Liu Qing , Duan Huigao , Liu Yanjun
Published: November 2019

Aluminum is one of the most significant plasmonic materials for its advantage of low cost, natural abundance, as well as the ultraviolet optical response. However, it is still very challengeable for the fabrication of aluminum plasmonic nanogaps, which greatly limits the applications of aluminum plasmonics considering the essential role of nanogaps for electric field enhancement. Here, the reliable patterning of aluminum plasmonic nanogaps employing a modified “Sketch and Peel” lithography strategy is demonstrated. By introducing a self‐assembled monolayer to engineer the surface energy of the substrate, the adhesiveness of the aluminum film outside outline template is significantly decreased to implement the selective peeling process. Besides, the near‐infrared Fano resonance in the periodic aluminum heptamers has been first revealed by enabling the strong electric field and plasmon coupling in the aluminum nanostructures with 10 nm scale nanogaps. In addition, surface‐enhanced Raman spectroscopy and infrared spectroscopy are also illustrated in the rationally designed aluminum dimers. The present work provides a robust method to obtain aluminum plasmonic nanogaps, which may play an important role on the practical applications of aluminum plasmonics, such as surface‐enhanced vibration spectroscopy and nonlinear optics.
Hydrocipher: Bioinspired Dynamic Structural Color‐Based Cryptographic Surface
Authors: Choi Jaeho , Hua Mutian , Lee Seung Yeol , Jo Wonhee , Lo Chiao‐Yueh , Kim Shin‐Hyun , Kim Hee‐Tak , He Ximin
Published: November 2019

Structural colors of 2D gratings are iridescent, color‐tunable, and never fade, which renders them appealing for anti‐counterfeiting applications. However, for advanced security, it still remains a challenge to completely hide the encrypted color patterns and reveal them on demand. In this work, a water‐responsive photonic grating consisting of a micropillar array and a hydrogel overcoat with a similar refractive index, termed “hydrocipher”, is presented. The joint effect of stimuli‐reversible refractive‐index (mis)match and reconfigurable grating‐based diffraction coloration enables a complete encryption of the structural color and rapid decryption. The photonic structure shows a strong iridescence due to the angle‐dependent diffraction when the hydrogel overcoat is swollen from water. Upon drying, the micropillars bend and the refractive index contrast disappears, which dramatically lessens the diffraction intensity and renders the surface highly transparent. The dehydrated‐to‐hydrated state transition can occur within 1 s, enabling fast decryption. The color switching is highly reversible over a prolonged hydration/dehydration cycle, and the dehydrated hydrogel layer protects the delicate micropillar array from external mechanical stress. The creative combination of hydrogel material and the 2D grating structure offers a new and simple strategy for realizing reversible, durable, and fast‐response cryptography with potentially broad impact on the anti‐counterfeiting technology market.
Cobalt Catalyzed Reductive Spirocyclopropanation Reactions
Authors: Werth Jacob , Berger Kristen , Uyeda Christopher
Published: November 2019

Cobalt pyridine−diimine (PDI) complexes catalyze the reductive spirocyclopropanation of terminal 1,3‐dienes. gem‐Dichlorocycloalkanes serve as carbene precursors and Zn is used as a terminal electron source. The reaction is effective for a range of gem‐dichloro partners including those containing sulfur and nitrogen heterocycles. An example of an intramolecular Rh‐catalyzed [5+2]‐cycloaddition of a vinyl spirocyclopropane is demonstrated, providing rapid access to a complex tricyclic framework. Overall, this catalyst system is capable of suppressing the kinetically facile 1,2‐hydride shift, which has hampered the development of Simmons−Smith reactions using Zn carbenoids possessing β‐hydrogen atoms.

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Proteome editing using engineered proteins that hijack cellular quality control machinery
Authors: Lopez‐Barbosa Natalia , Ludwicki Morgan B. , DeLisa Matthew P.
Published: November 2019

Protein silencing is an important aspect of both scientific investigation of native protein function and therapeutic targeting of aberrant protein activity. Many techniques for silencing proteins at the DNA or RNA level exist such as CRISPR, RNAi, or TALEN. Cellular proteins can also be selectively removed at the posttranslational level using proteome editing techniques, many of which employ engineered proteins to engage natural cellular quality control machinery for accelerating the removal of otherwise stable proteins. Here, we summarize recent progress in the development of such engineered proteins, comparing them to analogous microbial‐, viral‐, and small molecule‐based strategies for selectively degrading proteins of interest. Finally, we highlight the advantages and limitations of proteome editing technologies and discuss how the application of directed evolution could alleviate current challenges and usher in a new wave of designer proteins for diagnostic and therapeutic application.
Out‐of‐home care in childhood and biomedical risk factors in middle‐age: National birth cohort study
Authors: de Mestral Carlos , Bell Steven , Hamer Mark , Batty George David
Published: November 2019

Objective

With there being an apparent impact of experience of out‐of‐home care in childhood on chronic disease and mortality, we examined how such adversity might be embodied such that it has a measurable impact on human biology, so mediating this relationship.

Methods

We used data from the UK National Child Development Study in which exposure to public care was prospectively gathered on three occasions up to age 16. Study members also participated in a social survey at age 42 and a clinical examination at age 44/45 when cardiovascular, inflammatory, neuroendocrine, and respiratory risk markers for mortality were collected, 19 of which were included as endpoints in the present analyses.

Results

Of the 8012 participants in the biomedical survey, 4% (n = 322) had been in care at some point in childhood and/or adolescence. We found the expected marked differences in the early life characteristics of poverty, health, and disability in children with experience of public care relative to their unexposed counterparts. After controlling for these confounding factors, however, care in childhood was essentially unrelated to biomarkers in middle‐age. We also found no consistent links between these biomarkers and the duration, timing, or type of care.

Conclusions

Our results suggest that the biomarkers captured in the present study are unlikely to mediate the link between public care in childhood and later chronic disease or mortality. Processes involving mental health, socioeconomic position, and health behaviors would seem to be a potential alternative pathway warranting investigation.
Height and life satisfaction: Evidence from 27 nations
Authors: Habibov Nazim , Luo Rong , Auchynnikava Alena , Fan Lida
Published: November 2019

Objectives

To evaluate the effect of height on life satisfaction.

Methods

We use data from a recent multi‐country survey that was conducted in 27 nations.

Results

Our main finding is that height does have a strong positive effect on life satisfaction. These findings remain positive and significant when we use a comprehensive set of well‐known covariates of life‐satisfaction at both the individual and country levels. These findings also remain robust to alternative statistical specifications.

Conclusions

From a theoretical standpoint, our findings suggest that height is important in explaining life‐satisfaction independent of other well‐known determinants. From a methodological standpoint, the findings of this study highlight the need to explicitly control for the effect of heights in studies on subjective well‐being, happiness, and life‐satisfaction.
Adults with Loeys–Dietz syndrome and vascular Ehlers–Danlos syndrome: A cross‐sectional study of health burden perspectives
Authors: Johansen Heidi , Velvin Gry , Lidal Ingeborg
Published: November 2019

The aim is to study adults with vascular Ehlers–Danlos syndrome (vEDS) and Loeys–Dietz syndrome (LDS) with regard to sociodemographic characteristics, perceived vascular‐ and multi‐organ symptom burdens, and health services utilization. This is a cross‐sectional study. In 2018, a postal questionnaire was sent to 71 individuals with genetically verified LDS types 1–4 or vEDS, age ≥ 18 years, recruited through a National Resource Centre for Rare Disorders in Norway. Eighteen patients with vEDS and 34 patients with LDS subtypes 1‐4 participated, the response rate was 74%. Median age was 43.5 (range 18‐68) years, and 58% were women. Median age at diagnosis was 34 years (range: 6–63). Severe vascular‐ and multi‐organ symptom burdens were found, and chronic pain was reported by 79%. Most respondents (87%) had cardiovascular surveillance visits, 58% yearly or more often, and still 29% had no antihypertensive medications. Three quarters communicated diagnosis‐related concerns with their general practitioner. A considerable group (31%) had left work before retirement age. Healthcare professionals should be aware of the spectrum of health burden in adults with vEDS and LDS. A verification of the diagnosis is crucial to counseling, including medical follow‐up, education, and work, and advices on precaution and life style decisions.
Extending the phenotypic spectrum of Bohring‐Opitz syndrome: Mild case confirmed by functional studies
Authors: Leon Eyby , Diaz Jullianne , Castilla‐Vallmanya Laura , Grinberg Daniel , Balcells Susanna , Urreizti Roser
Published: November 2019

Bohring‐Opitz syndrome (BOS) has been described as a clinically recognizable genetic syndrome since 1999. Clinical diagnostic criteria were established in 2011 and include microcephaly, trigonocephaly, distinctive craniofacial dysmorphic features, facial nevus flammeus, failure to thrive, and severe developmental delays. The same year, different de novo heterozygous nonsense mutations in the ASXL1 were found in affected individuals. Since then, several cases have been reported confirming the association between this chromatin remodeling gene and BOS. Most affected individuals die in early childhood because of unexplained bradycardia, obstructive apnea, or pulmonary infections. Those that survive usually cannot walk independently and are nonverbal. Some have had success using walkers and braces in late childhood. While few are able to speak, many have been able to express basic needs using communication devices as well as gestures with associated basic vocalizations. In this article, we present a mild case of BOS with a de novo pathogenic mutation c.1720‐2A>G (p.I574VfsX22) in ASXL1 detected on whole‐exome sequencing and confirmed by functional analysis of the messenger RNA splicing pattern on the patient's fibroblasts. She has typical dysmorphic features and is able to run and walk independently as well as to communicate with basic sign language.
HELLP syndrome: An ultrasound case of geographically altered liver parenchymal echogenicity with shear wave elastography, shear wave dispersion and attenuation imaging correlation
Authors: Mould Andrea , Abbott Steven , Welman Christopher J.
Published: November 2019

HELLP syndrome is a rare, potentially life threatening obstetric condition that is diagnosed by the combination of Haemolysis, Elevated Liver enzyme levels, and Low Platelets (Pregnancy Hypertens, 1, 164, 2011). HELLP affects between 0.5% and 0.9% of all pregnancies (BMC Pregnancy Childbirth, 9, 8, 2009), however less than 0.5% of HELLP syndrome cases demonstrate any imaging abnormalities (Am J Roentgenol 185, 1205, 2005). This case report outlines the use of three new liver ultrasound technologies – shear wave elastography (SWE), shear wave dispersion (SWD) and attenuation imaging (ATI) in the evaluation of a patient with HELLP syndrome. The ultrasound applications were used to examine temporal changes of the disease with corresponding biochemical variations. The SWE and SWD values correlated with B mode ultrasound imaging and the clinical findings of HELLP.
Receptor activator of nuclear factor κB ligand is a biomarker for osteitis of chronic rhinosinusitis
Authors: Kong Il Gyu , Kim Dong‐Kyu , Eun Kyoung Mi , Yang Seung Koo , Kim Minju , Oh Heonjeong , Kim Dae Woo
Published: November 2019

Background

Evidence of osteitis is frequently observed in patients with chronic rhinosinusitis (CRS), especially in recalcitrant cases. However, studies focusing on biological markers of osteitis are limited and it remains unclear whether osteitis is associated with different phenotypes of CRS. This study aimed to analyze the expression and assess the roles of receptor activator of nuclear factor κB ligand (RANKL) in patients with CRS and osteitis.

Methods

CRS patients with nasal polyps (CRSwNP, n = 63), CRS patients without nasal polyps (CRSsNP, n = 8), and control subjects (n = 12) were enrolled. Histologic phenotypes, clinical information, and computed tomography (CT) scores were investigated. The Global Osteitis Scoring Scale (GOSS) and RANKL, a molecular marker of bone remodeling, were analyzed in each type of CRS. CRS mouse models were treated with anti‐RANKL.

Results

GOSS values were significantly higher in all CRS patients than in the control group. The GOSS value in non‐eosinophilic CRSwNP was higher than in eosinophilic CRSwNP. RANKL was upregulated whereas decoy receptor osteoprotegerin (OPG) was downregulated in CRS. RANKL messenger RNA (mRNA) and protein levels were positively correlated with GOSS. RANKL/OPG was increased in recurrent cases compared with primary cases. Multiple inflammatory mediators were positively correlated with the protein level of RANKL in CRS tissues. In the mouse CRSwNP model, anti‐RANKL treatment abrogated mucosal inflammation and bone remodeling.

Conclusion

RANKL expression is associated with clinical osteitis and disease severity in CRSwNP. These findings shed light on the importance of RANKL as a potential biomarker of CRS and a key player in CRS pathogenesis.
Homogeneous Oligomeric Ligands Prepared via Radical Polymerization that Recognize and Neutralize a Target Peptide
Authors: Hoshino Yu , Taniguchi Shohei , Takimoto Hinata , Akashi Sotaro , Katakami Sho , Yonamine Yusuke , Miura Yoshiko
Published: November 2019

Abiotic ligands that bind to specific biomolecules have attracted attention as substitutes for biomolecular ligands, such as antibodies and aptamers. Radical polymerization enables the production of robust polymeric ligands from inexpensive functional monomers. However, little has been reported about the production of monodispersed polymeric ligands. Herein, we present homogeneous ligands prepared via radical polymerization that recognize epitope sequences on a target peptide and neutralize the toxicity of the peptide. Taking advantage of controlled radical polymerization and separation, a library of multifunctional oligomers with discrete numbers of functional groups was prepared. Affinity screening revealed that the sequence specificity of the oligomer ligands strongly depended on the number of functional groups. The process reported here will become a general step for the development of abiotic ligands that recognize specific peptide sequences.
Effective Utilization of NIR Wavelengths for Photo‐Controlled Polymerization: Penetration Through Thick Barriers and Parallel Solar Syntheses
Authors: Wu Zilong , Jung Kenward , Boyer Cyrille
Published: November 2019

This contribution details an efficient and controlled photopolymerization regulated by far‐red (λ=680 nm) and NIR (λ=780 and 850 nm) light in the presence of aluminium phthalocyanine and aluminium naphthalocyanine. Initiating radicals are generated by photosensitization of peroxides affording an effective strategy that provides controlled polymerization of a variety of monomers with excellent living characteristics. Critically, long wavelength irradiation provides penetration through thick barriers, affording unprecedented rates of controlled polymerization that can open new and exciting applications. Furthermore, a more optimized approach to performing solar syntheses is presented. By combining the narrow Q‐bands of these photocatalysts with others possessing complementary absorptions, layered, independent polymerizations and organic transformations may be performed in parallel under a single broadband emission source, such as sunlight.
Single Chromium Atoms Supported on Titanium Dioxide Nanoparticles for Synergic Catalytic Methane Conversion under Mild Conditions
Authors: Shen Qikai , Cao Changyan , Huang Runkun , Zhu Lei , Zhou Xin , Zhang Qinghua , Gu Lin , Song Weiguo
Published: November 2019

Direct conversion of methane to value‐added chemicals with high selectivity under mild conditions remains a great challenge in catalysis. Now, single chromium atoms supported on titanium dioxide nanoparticles are reported as an efficient heterogeneous catalyst for direct methane oxidation to C1 oxygenated products with H2O2 as oxidant under mild conditions. The highest yield for C1 oxygenated products can be reached as 57.9 mol molCr−1 with selectivity of around 93 % at 50 °C for 20 h, which is significantly higher than those of most reported catalysts. The superior catalytic performance can be attributed to the synergistic effect between single Cr atoms and TiO2 support. Combining catalytic kinetics, electron paramagnetic resonance, and control experiment results, the methane conversion mechanism was proposed as a methyl radical pathway to form CH3OH and CH3OOH first, and then the generated CH3OH is further oxidized to HOCH2OOH and HCOOH.
Intermolecular Stereospecific Substitution of Underivatized Enantioenriched Secondary Alcohols by Organocatalysis
Authors: Akkarasamiyo Sunisa , Samec Joseph S. M.
Published: November 2019

The stereospecific substitution of non‐derivatized and non‐allylic enantioenriched alcohols with only water as a by‐product would enable the use of readily available alcohols as substrates for green and sustainable transformations. However, the poor leaving group ability of the OH group has hampered the development of such a process. Denton and co‐workers recently described the use of (2‐hydroxybenzyl)diphenylphosphine oxide as a catalyst of a redox‐neutral and zero‐waste‐generating Mitsunobu reaction. This innovative process constitutes the first intermolecular stereospecific substitution of non‐allylic alcohols, and might find industrial applications.
Gold(III) π‐Allyl Complexes
Authors: Rodriguez Jessica , Szalóki György , Sosa Carrizo E. Daiann , Saffon‐Merceron Nathalie , Miqueu Karinne , Bourissou Didier
Published: November 2019

Gold(III) π‐complexes have been authenticated recently with alkenes, alkynes, and arenes. The key importance of PdII π‐allyl complexes in organometallic chemistry (Tsuji–Trost reaction) prompted us to explore gold(III) π‐allyl complexes, which have remained elusive so far. The (P,C)AuIII(allyl) and (methallyl) complexes 3 and 3′ were readily prepared and isolated as thermally and air‐stable solids. Spectroscopic and crystallographic analyses combined with detailed DFT calculations support tight quasi‐symmetric η3‐coordination of the allyl moiety. The π‐allyl gold(III) complexes are activated towards nucleophilic additions, as substantiated with β‐diketo enolates.
A Supported Nickel Catalyst Stabilized by a Surface Digging Effect for Efficient Methane Oxidation
Authors: Zhou Huang , Liu Tianyang , Zhao Xuyan , Zhao Yafei , Lv Hongwei , Fang Shi , Wang Xiaoqian , Zhou Fangyao , Xu Qian , Xu Jie , Xiong Can , Xue Zhenggang , Wang Kai , Cheong Weng‐Chon , Xi Wei , Gu Lin , Yao Tao , Wei Shiqiang , Hong Xun , Luo Jun , Li Yafei , Wu Yuen
Published: November 2019

A surface digging effect of supported Ni NPs on an amorphous N‐doped carbon is described, during which the surface‐loaded Ni NPs would etch and sink into the underneath carbon support to prevent sintering. This process is driven by the strong coordination interaction between the surface Ni atoms and N‐rich defects. In the aim of activation of C−H bonds for methane oxidation, those sinking Ni NPs could be further transformed into thermodynamically stable and active metal‐defect sites within the as‐generated surface holes by simply elevating the temperature. In situ transmission electron microscopy images reveal the sunk Ni NPs dig themselves adaptive surface holes, which would largely prevent the migration of Ni NPs without weakening their accessibility. The reported two‐step strategy opens up a new route to manufacture sintering‐resistant supported metal catalysts without degrading their catalytic efficiency.
Total Synthesis of (+)‐6‐epi‐Ophiobolin A
Authors: Thach Danny Q. , Brill Zachary G. , Grover Huck K. , Esguerra Kenneth V. , Thompson Jordan K. , Maimone Thomas J.
Published: November 2019

The ophiobolin sesterterpenes are notable plant pathogens which have recently elicited significant chemical and biological attention because of their intriguing carbogenic frameworks, reactive functionalities, and emerging anticancer profiles. Reported herein is a total synthesis of (+)‐6‐epi‐ophiobolin A in 14 steps, a task which addresses construction of the synthetically challenging spirocyclic tetrahydrofuran motif as well as several other key stereochemical problems. This work demonstrates a streamlined synthetic platform to complex ophiobolins leveraging disparate termination modes of a radical polycyclization cascade for divergent elaboration and functionalization.
Glycidols Esters, 2‐Chloropropane‐1,3‐Diols, and 3‐Chloropropane‐1,2‐Diols Contents in Real Olive Oil Samples and their Relation with Diacylglycerols
Authors: Cichelli Angelo , Riciputi Ylenia , Cerretani Lorenzo , Caboni Maria F. , d'Alessandro Nicola
Published: November 2019

A series of authentic virgin, refined, and mixtures of olive oils was analyzed for their content of 2‐and 3‐chloropropanediol (MCPD) esters expressed as 2−/3‐MCPD, glycidol (and related glycidyl esters) (GE), and diglycerides (DAG). High concentrations of MCPD and GE were found, above all, in pomace oils, which come from the poorer starting raw materials, while virgin olive oils, as expected, do not contain any process contaminant. On the other hand, DAGs are present in all samples, demonstrating that their involvement in the formation of such contaminants only occurs when temperatures are higher than that used during the refining steps. The lack of correlation between the amounts of MCPD and GE can be ascribed to their completely different chemical stability as the epoxy ring of the GE opens easily, leading to both short‐chain derivatives and/or MCPD itself. This finding can also explain the data about the absence of 2‐MCPD in all the analyzed oil samples: other than the statistical probability and the steric effect of the SN2 formation mechanism, both in favor of the 3‐ derivative, we have also to consider the MCPD formation pathway involving glycidol that, under opportune conditions of refining, can increase the whole amount of 3‐MCPD (under thermodynamic control, 3‐MCPD is more stable).
Preparation of a NiAl‐Oxide@Polypyrrole Composite for High‐Performance Supercapacitors
Authors: Zou Kai‐Min , Zeng Hong‐Yan , Cao Xiao‐Ju , Yuan Jian , Claude Alain Gohi Bi Foua , Xu Sheng , Li Hao‐Bo , Long Yi‐Wen
Published: November 2019

A core‐shell NiAlO@polypyrrole composite (NiAlO@PPy) with a 3D “sand rose”‐like morphology was prepared via a facile in situ oxidative polymerization of pyrrole monomer, where the role of PPy coating thickness was investigated for high‐performance supercapacitors. Microstructure analyses indicated that the PPy was successfully coated onto the NiAlO surface to form a core‐shell structure. The NiAlO@PPy exhibited a better electrochemical performance than pure NiAlO, and the moderate thickness of the PPy shell layer was beneficial for expediting the electron transfer in the redox reaction. It was found that the NiAlO@PPy5 prepared at 5.0 mL L−1 addition amount of pyrrole monomer demonstrated the best electrochemical performance with a high specific capacitance of 883.2 F g−1 at a current density of 1 A g−1 and excellent capacitance retention of 91.82 % of its initial capacitance after 1000 cycles at 3 A g−1. The outstanding electrochemical performance of NiAlO@PPy5 were due to the synergistic effect of NiAlO and PPy, where the uniform network‐like PPy shell with the optimal thickness made electrolyte ions more easily accessible for faradic reactions. This work provided a simple approach for designing organic–inorganic core‐shell materials as high‐performance electrode materials for electrochemical supercapacitors.
Ginkgolide B protects human pulmonary alveolar epithelial A549 cells from lipopolysaccharide‐induced inflammatory responses by reducing TRIM37‐mediated NF‐κB activation
Authors: Xiang Yijin , Zhang Shaoyan , Lu Jia , Zhang Wen , Cai Min , Xiang Jun , Cai Dingfang
Published: November 2019

The treatment options for acute stroke combined with pulmonary infection are limited. Clinically, there are several therapies to promote blood circulation and dissipate blood stasis; these treatment options include ginkgolide B (GB), which has PAF (platelet activating factor)‐inhibiting effects. PAF‐receptor (PAF‐R) antagonists are used to treat a variety of inflammatory diseases; however, the potential of PAF‐R antagonists as a treatment for lung infections remains unclear. The aim of the present study is to investigate the protective effect of GB on lipopolysaccharide‐induced inflammatory responses in A549 human pulmonary alveolar epithelial cells (HPAEpiC) in vitro. Cell viability and apoptosis were measured by CCK‐8 and flow cytometry. TRIM37, Caspase‐3, and NF‐κBp65 expression levels were measured by real‐time PCR and Western blotting. The release of tumor necrosis factor‐α and interleukin‐1β was measured by ELISA. The data indicates that GB may reduce TRIM37 expression by antagonizing the PAF‐R pathway, thereby inhibiting the activation of nuclear factor‐κB and alleviating the inflammatory response of alveolar epithelial cells. This study is the first to provide insight into the therapeutic potential of GB and suggests that clinical application of GB in acute stroke combined with pulmonary inflammation may be efficacious.
Fiber Electronics: An Emerging Field
Authors: Peng Huisheng
Published: November 2019

Huisheng Peng
is a Professor at the Department of Macromolecular Science and Laboratory of Advanced Materials at Fudan University. He is one of the Editorial Board Members of Batteries & Supercaps.
Adult and infant pharmacokinetic profiling of dihydrocodeine using physiologically based pharmacokinetic modeling
Authors: Ota Miki , Shimizu Makiko , Kamiya Yusuke , Emoto Chie , Fukuda Tsuyoshi , Yamazaki Hiroshi
Published: November 2019

We previously analysed the serum concentrations of dihydrocodeine in a 1‐month‐old infant with respiratory depression after being prescribed dihydrocodeine phosphate 2.0 mg/day divided t.i.d. for 2 days. The purpose was to develop a full physiologically based pharmacokinetic (PBPK) model that could account for these and other drug monitoring results. Based on experiments in Caco‐2 cell monolayers, the effective permeability of dihydrocodeine in human jejunum was established as 1.28 × 10−4 cm/s. The in vitro Vmax/Km values for dihydrocodeine demethylation mediated by recombinant cytochrome P450 2D6 and 3A4 were 0.19 and 0.066 μl/min/pmol, respectively, and for dihydrocodeine 6‐O‐glucuronidation mediated by recombinant UGT2B4 and 2B7, the Vmax/Km values were 0.14 and 0.22 μl/min/mg protein, respectively. Renal clearance was calculated as 5.37 L/h on the total clearance value multiplied by the fraction recovered in urine. The reported plasma concentration–time profiles of dihydrocodeine after intravenous administration in healthy volunteers were used to adjust the tissue partitioning ratios. The developed model simulated the pharmacokinetic profiles of dihydrocodeine after single and multiple oral administrations reasonably well in the same population. Subsequently, the validated model was used to simulate pharmacokinetic profiles for five pediatric cases, including the 1‐month‐old Japanese boy and a 14‐year‐old Japanese girl who took an overdose of dihydrocodeine phosphate (37 mg). The simulated pharmacokinetic profiles for five virtual pediatric subjects matching the age, gender, and P450 2D6 phenotype of each case approximately reflected the observed values. These results suggested that our dihydrocodeine PBPK model reproduced the results of clinical cases reasonably well for subjects.
Can Designer Indels Be Tailored by Gene Editing?
Authors: Trimidal Sara G. , Benjamin Ronald , Bae Ji Eun , Han Mira V. , Kong Elizabeth , Singer Aaron , Williams Tyler S. , Yang Bing , Schiller Martin R.
Published: November 2019

Genome editing with engineered nucleases (GEENs) introduce site‐specific DNA double‐strand breaks (DSBs) and repairs DSBs via nonhomologous end‐joining (NHEJ) pathways that eventually create indels (insertions/deletions) in a genome. Whether the features of indels resulting from gene editing could be customized is asked. A review of the literature reveals how gene editing technologies via NHEJ pathways impact gene editing. The survey consolidates a body of literature that suggests that the type (insertion, deletion, and complex) and the approximate length of indel edits can be somewhat customized with different GEENs and by manipulating the expression of key NHEJ genes. Structural data suggest that binding of GEENs to DNA may interfere with binding of key components of DNA repair complexes, favoring either classical‐ or alternative‐NHEJ. The hypotheses have some limitations, but if validated, will enable scientists to better control indel makeup, holding promise for basic science and clinical applications of gene editing. Also see the video abstract here https://youtu.be/vTkJtUsLi3w
Three‐dimensional biomimetic hyaluronic acid hydrogels to investigate glioblastoma stem cell behaviors
Authors: Nakod Pinaki S. , Kim Yonghyun , Rao Shreyas S.
Published: November 2019

Glioblastoma multiforme (GBM) is the deadliest form of primary brain tumor. GBM tumors are highly heterogeneous, being composed of tumor cells as well as glioblastoma stem cells (GSCs) that contribute to drug resistance and tumor recurrence following treatment. To develop therapeutic strategies, an improved understanding of GSC behavior in their microenvironment is critical. Herein, we have employed three‐dimensional (3D) hyaluronic acid (HA) hydrogels that allow the incorporation of brain microenvironmental cues to investigate GSC behavior. U87 cell line and patient‐derived D456 cells were cultured as suspension cultures (serum‐free) and adherently (in the presence of serum) and were then encapsulated in HA hydrogels. We observed that all the seeded single cells expanded and formed spheres, and the size of the spheres increased with time. Increasing the initial cell seeding density of cells influenced the sphere size distribution. Interestingly, clonal expansion of serum‐free grown tumor cells in HA hydrogels was observed. Also, stemness marker expression of serum and/or serum‐free grown cells was altered when cultured in HA hydrogels. Finally, we demonstrated that HA hydrogels can support long‐term GSC culture (up to 60 days) with retention of stemness markers. Overall, such biomimetic culture systems could further our understanding of the microenvironmental regulation of GSC phenotypes.
Multiple organ dysfunction after trauma
Authors: Cole E , Gillespie S , Vulliamy P , Brohi K , Akkad H , Apostolidou K , Ardley R , Aylwin C , Bassford C , Bonner S , Brooks A , Cairns T , Cecconi M , Clark F , Dempsey G , Denison Davies E , Docking R , Eddlestone J , Ellis D , Evans J , Galea M , Healy M , Horner D , Howarth R , Jansen J , Jones J , Kaye C , Keep J , Kerslake D , Kilic J , Leong M , Martinson V , McIldowie B , Michael S , Millo J , Morgan M , O'Leary R , Oram J , Ortiz-Ruiz De Gordoa L , Porter K , Raby S , Service J , Shaw D , Smith J D , Smith N , Stotz M , Thomas E , Thomas M , Vincent A , Ward G , Welters I
Published: November 2019

Background

The nature of multiple organ dysfunction syndrome (MODS) after traumatic injury is evolving as resuscitation practices advance and more patients survive their injuries to reach critical care. The aim of this study was to characterize contemporary MODS subtypes in trauma critical care at a population level.

Methods

Adult patients admitted to major trauma centre critical care units were enrolled in this 4-week point-prevalence study. MODS was defined by a daily total Sequential Organ Failure Assessment (SOFA) score of more than 5. Hierarchical clustering of SOFA scores over time was used to identify MODS subtypes.

Results

Some 440 patients were enrolled, of whom 245 (55·7 per cent) developed MODS. MODS carried a high mortality rate (22·0 per cent versus 0·5 per cent in those without MODS; P < 0·001) and 24·0 per cent of deaths occurred within the first 48 h after injury. Three patterns of MODS were identified, all present on admission. Cluster 1 MODS resolved early with a median time to recovery of 4 days and a mortality rate of 14·4 per cent. Cluster 2 had a delayed recovery (median 13 days) and a mortality rate of 35 per cent. Cluster 3 had a prolonged recovery (median 25 days) and high associated mortality rate of 46 per cent. Multivariable analysis revealed distinct clinical associations for each form of MODS; 24-hour crystalloid administration was associated strongly with cluster 1 (P = 0·009), traumatic brain injury with cluster 2 (P = 0·002) and admission shock severity with cluster 3 (P = 0·003).

Conclusion

Contemporary MODS has at least three distinct types based on patterns of severity and recovery. Further characterization of MODS subtypes and their underlying pathophysiology may lead to future opportunities for early stratification and targeted interventions.
Reduced central sympathetic activity in Parkinson's disease
Authors: Krämer Heidrun H. , Lautenschläger Gothje , de Azevedo Michael , Doppler Kathrin , Schänzer Anne , Best Christoph , Oertel Wolfgang H. , Reuter Iris , Sommer Claudia , Birklein Frank
Published: November 2019

Objective

With a combination of different sympathetic tests, we aimed to elucidate whether impairment of sympathetic function in Parkinson's disease (PD) is the consequence of a central or peripheral efferent dysfunction.

Methods

Thirty‐five patients with early‐to‐intermediate PD (median age: 63 years; IQR: 57–67 years; disease duration 1–9 years, 15 women) and 20 age‐ and sex‐matched healthy controls (median age: 64.5 years; IQR: 58–68 years; 10 women) were recruited. Autonomic testing was performed in two subgroups and included the assessment of resting cardiovascular parameters, postprandial hypotension (PPH), orthostatic hypotension (OH), and vasoconstriction induced by intradermal microdialysis with different concentrations of norepinephrine (NE; 10–5; 10–6; 10–7; 10–8) and by cold through forehead cooling. We also used sympathetic multiunit microneurography (muscle sympathetic nerve activity; MSNA; burst frequency (BF): bursts per minute; burst incidence (BI): bursts per 100 heart beats) and evaluated the presence of phosphorylated α‐synuclein deposits in skin innervation in biopsies from the thighs by immunohistohemistry.

Results

Diastolic blood pressure was higher in the PD group at rest (p < .001) and during OH (F = 6.533; p = .022). Vasoconstriction induced by NE microdialysis and cold was unchanged in PD patients. MSNA was lower in PD patients than in controls (BF: p = .001; BI: p = .025). Phosphorylated α‐synuclein deposits could be found only in PD patients.

Conclusion

We did not find indications for peripheral sympathetic nerve fiber dysfunction or adrenoreceptor sensitivity changes. The decreased MSNA argues in favor of central sympathetic impairment.
TAE226, a dual inhibitor of focal adhesion kinase and insulin‐like growth factor‐I receptor, is effective for Ewing sarcoma
Authors: Moritake Hiroshi , Saito Yusuke , Sawa Daisuke , Sameshima Naoki , Yamada Ai , Kinoshita Mariko , Kamimura Sachiyo , Konomoto Takao , Nunoi Hiroyuki
Published: November 2019

The outcomes for relapsed and metastatic Ewing sarcoma (EWS) is extremely poor. Therefore, it is important to identify the tumor‐specific targets in these intractable diseases. High focal adhesion kinase (FAK) transcript expression levels in EWS cell lines are known. TAE226 is a dual inhibitor of FAK and insulin‐like growth factor‐I receptor (IGF‐IR), while PF‐562,271 is a dual inhibitor of FAK and proline‐rich tyrosine kinase 2. We compared the cytotoxicity of TAE226 and PF‐562,271 toward three EWS cell lines. TAE226 strongly inhibited proliferation of three cell lines when compared with PF‐562,271. Furthermore, we investigated the efficacy of TAE226 as well as its mechanism of action against EWS. A stable EWS cell line with FAK and IGF‐IR knocked down was established, and microarray analysis revealed dysregulated expression in various pathways. TAE226 treatment of EWS cell lines induced cell cycle arrest, apoptosis, AKT dephosphorylation, and inhibition of invasion. We demonstrated that TAE226 drastically inhibits the local growth of primary tumors and metastasis in EWS using mouse models. Furthermore, the combination of TAE226 and conventional chemotherapy proved to exert synergistic effects. TAE226 may be a candidate single agent or combined therapy drug to be developed for patients who have relapse and metastatic EWS tumors in future.