bluuebunny/crossref_metadata_2025 huggingface dataset:
Unparalleled Dielectric‐Switching Effects Caused by Dual Polarization Synergy
Authors: Gong Yutie , Zhao Jiayu , Li Zhenzhen , Huang Jing , Zhang Yang , Dong Lijie , Xiong Chuanxi , Jiang Ming
Published: April 2023

Dielectric switching materials are prospective candidates for smart electronic/electrical applications, and high dielectric switching ratios are crucial for their practical applications. However, the substantial improvement of the dielectric switching ratio is limited by the available dielectric switching mechanisms, and obtaining high dielectric switching ratios is a major challenge. Here, an unparalleled dielectric switching effect is reported in a water‐in‐oil emulsion system, caused by dual polarization synergy below the dielectric transition temperature in concert with suppression of the electrode polarization above the dielectric transition temperature. The synergistic dielectric switching effect of interfacial polarization and electrode polarization endows the emulsion with unprecedentedly high dielectric switching ratios. The highest room temperature dielectric switching ratio of this emulsion system up to 2.86 × 106 at 20 Hz, is four orders of magnitude higher than the highest switching ratio reported so far. The unparalleled high dielectric switching ratio, reliable cycle stability, good frequency adaptability, and satisfactory scalability make the inorganic salt solution/octadecane emulsions potentially excellent candidates for high‐sensitivity room‐temperature smart switching or sensing devices.
Nonlinear Terahertz Generation: Chiral and Achiral Meta‐Atom Coupling
Authors: Wang Qingwei , Zhang Xueqian , Xu Quan , Feng Xi , Lu Yongchang , Niu Li , Chen Xieyu , Plum Eric , Gu Jianqiang , Yang Quanlong , Fang Ming , Huang Zhixiang , Zhang Shuang , Han Jiaguang , Zhang Weili
Published: April 2023

Generation and manipulation of terahertz (THz) waves are of vital importance for advancing THz technology. Nonlinear metasurfaces allow effective integration of both processes into a single compact device. However, such existing THz devices commonly rely on utilizing a single meta‐atom, which has fixed THz generation properties and thus limits the range of achievable functionalities. Here, it is demonstrate how coupling between different meta‐atoms within the unit‐cell can be used as a degree of freedom for controlling nonlinear THz generation, where achiral coupling provides full control over the amplitude of the generated THz field, while chiral coupling makes the THz generation sensitive to the handedness of the pump polarization. In particular, chiral coupling allows the realization of multiplexed pump‐handedness‐selective nonlinear metasurfaces, which is illustrated experimentally by selectively generating THz beams with different orbital angular momentum with a single nonlinear metasurface. This approach provides opportunities for developing various integrated nonlinear THz devices.
FIB‐SEM and ToF‐SIMS Analysis of High‐Temperature PEM Fuel Cell Electrodes
Authors: Braig Michael , Deissler Niklas H. , Lüdeking Ildiko , Regnet Fabian , Bevilacqua Nico , Zeis Roswitha
Published: April 2023

The phosphoric acid (PA) distribution in the electrodes is a crucial factor for the performance of high‐temperature polymer electrolyte fuel cells (HT‐PEM FCs). Therefore, understanding and optimizing the electrolyte distribution is vital to maximizing power output and achieving low degradation. Although challenging, tracking the PA in nanometer‐sized pores is essential because most active sites in the commonly used carbon black‐supported catalysts are located in pores below 1 µm. For this study, a cell is operated at 200 mA cm−2 for 5 days. After this break‐in period, the cathode is separated from the membrane electrode assembly and subsequently investigated by cryogenic focused ion beam scanning electron microscopy (cryo FIB‐SEM) coupled with energy‐dispersive X‐ray spectroscopy (EDX) and time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS). PA is located on the surface and in the bulk of the cathode catalyst layer. In addition, the PA distribution can be successfully linked to the gas diffusion electrode morphology and the binder distribution. The PA preferably invades nanometer‐sized pores and is uniformly distributed in the catalyst layer.
Miniature Transparent Dopamine Sensor Based on Nanosphere Lithography
Authors: Kim Yoojeong , Jang Eunyoung , Lee Youngsun , Oh Chaerin , Kim Kiup , Kook Geon , Kim Mi Kyung , Lee Mi‐Ok , Lee Hyunjoo J.
Published: April 2023

Detection of neurotransmitters for in vitro analysis systems is an essential component in evaluating the integrity and viability of in vitro models of neurodegenerative disorders and the cytotoxicity of drug candidates. Currently, electrochemical analysis such as cyclic voltammetry (CV) is the most widely used method for the detection of neurotransmitters. However, while most in vitro analysis systems are based on optical imaging, electrochemical sensors are non‐transparent and hinder in situ simultaneous cell monitoring. In this work, a highly sensitive miniaturized electrochemical sensor that is also transparent is proposed, which enables simultaneous dopamine detection and in vitro optical assays. The microfabrication process and nanosphere lithography are utilized to fabricate a transparent working electrode. The transparent electrode is functionalized with the overoxidized polypyrrole/sodium dodecyl sulfate‐modified carbon nanotube (OPPy/SDS‐CNT). The detection of DA is successfully demonstrated using the miniaturized transparent sensor. In addition, the PC‐12 cell is cultured in the sensor‐integrated chamber and the cell viability is confirmed on the sensor over 3 days. The proposed miniature transparent  sensor is a great candidate for next‐generational multi‐modal in vitro analysis systems.
Color‐Tunable Eu3+, Eu2+‐Activated CaSiO3 Nano Phosphor Extract from Agricultural‐Recycling‐Food‐Waste Materials for Display Applications
Authors: Krishnam Raju M. , Samudrala Raj Kumar , Yadav Pooja , Azeem P. Abdul
Published: April 2023

A series of Eu3+ and Eu2+ doped wollastonite is produced with a modified sol–gel technique using agricultural‐food waste materials. Rice husk ash (RHA) and eggshell (ES) are used as an usher for silica and calcium oxide, appropriately, at different concentrations (0.0, 0.2, 0.4, 0.6, 0.8, and 1 mol%). Most investigations have documented photoluminescence (PL) from Eu3+ ions caused by electronic transitions between 4f levels (5D0 → 7FJ) but there is limited information on emissions from Eu2+ ions. Fourier transform infrared (FTIR) spectra and X‐ray diffraction (XRD) studies reveal that varying amounts of europium ions do not have any effect on the structure of the host. PL spectra display that europium ions exist in both trivalent and divalent forms. A valence change from Eu3+ to Eu2+ ion is investigated using luminescence measurements. As‐prepared Eu3+ activated β‐wollastonite emitted as red and reduction atmosphere using argon gas produced Eu2+ activated phosphor gives off blue light. X‐Ray photoelectron spectroscopy reveals that throughout the processing of the samples, Eu3+ cations are partially reduced to Eu2+ cations in argon gas atmosphere. These findings prove the feasibility of fabricating white light‐emitting diodes (white‐LEDs) for three‐band type (RGB) phosphors utilizing only one host crystal.
Slow‐Light‐Based Dispersion Compensation of High‐Speed Data on a Silicon Nitride Chip
Authors: Ong Kenny Yong Keng , Chen George Feng Rong , Choi Juwon , Tan Dawn T. H.
Published: April 2023

Transmission of optical data over fiber is subjected to signal degradation from dispersion impairments that worsen with increasing fiber lengths and higher data rates. Consequently, dispersion impairments significantly limit the data rates and reaches of transceivers used for data center communications. Herein, the design and experimental demonstration of a low loss, CMOS‐compatible on‐chip silicon nitride transmission grating device for dispersion compensation of high‐speed data are reported. The design, which involves inscribing a perturbation in the effective index profile of the grating, generates a considerable increase in the dispersion magnitude and enables up to 25 km of single‐mode fiber to be compensated for. Importantly, high‐speed measurements after dispersion compensation of a 20 km single‐mode fiber, using non‐return‐to‐zero data at rates up to 28.05 Gb s−1 show nine orders of magnitude reduction in BERs from 5  10−1 to 1  10−10, accompanied by significant improvements in the eye diagram. The underlying operating mechanism involves slow‐light effects that are designed to generate large dispersion while maintaining low losses. A pathway toward dispersion impairment‐free high‐speed data transmission over fiber using a compact device is demonstrated, which can be seamlessly integrated within transceiver chips, bringing the applicability of slow‐light devices firmly into the domain of commercial viability.
Tailoring Electromagnetic Responses in Terahertz Metasurface by Breaking the Structural Symmetry in T‐Shaped Resonators
Authors: Liu Changxiang , Li Dongsheng , Boutinaud Philippe , Xu Jie , Du Yongping , Hou Yidong , Zhang Cunlin , Zhou Qingli , Kang Fengwen
Published: April 2023

Herein, the design of terahertz metasurface with symmetric T‐shaped resonators and the corresponding bright and dark modes are reported on. It is demonstrated that the dark mode evoked by breaking the structural symmetry is insensitive to the X‐polarized electric field and a typical electromagnetically induced transparency (EIT) effect is also observed in the numerical simulation when introducing a relatively low structural asymmetry where the dark and bright modes are modified to the same frequency. To explain the underlying mechanism, theoretical calculations based on the coupled Lorentz oscillator model are performed. In terms of the desirable fittings with the simulation results, it is confirmed that there exists the dark mode in the symmetric T‐shaped resonators and the coupling between the bright and dark modes enhanced by the structural–symmetry breaking is responsible for the observed EIT effect. It is shown in the results further that the structural asymmetry degree has close relation with the coupling strength resonance and can thereby greatly affect the oscillation resonance splitting in frequency that it is reflected by the change of the bandwidth of the transparency window. In addition, the experimental spectra showing the characteristic of broadband transparency window are explained by the excitation of the dark mode whose frequency deviates from the bright mode.
Tailoring the Electronic Structure of Ir Alloy Electrocatalysts through Lanthanide (La, Ce, Pr, and Nd) for Acidic Oxygen Evolution Enhancement
Authors: Zhang Shuai , Sun Mingzi , Yin Leilei , Wang Siyuan , Huang Bolong , Du Yaping , Yan Chun-Hua
Published: April 2023

The oxygen evolution reaction (OER) is critical for renewable energy conversion and storage devices. However, the rational design of electrocatalysts with suitably high efficiency and stability in strongly acidic electrolytes remains a major challenge. Herein, a solid‐phase synthesis strategy is developed for the preparation of Ir‐Ln (Ln = La, Ce, Pr, Nd) alloy nanoparticles with uniform particle size on carbon supports as superior acidic OER catalysts. Tailoring by the rare earth (RE) elements, Ir2Pr achieves a maximum mass activity of 2.10 A mg−1Ir at 300 mV overpotential and stability over 200 h at 10 mA cm−2 in 0.5 m H2SO4, which is 9.5 and 20 times higher to pure Ir nanoparticles. Furthermore, Ir2Pr alloy nanoparticles exhibit excellent durability in strongly acidic electrolytes. Theoretical calculations have confirmed that the OER performances are strongly related to the RE elements in the alloy, where the d‐band centers show a consistent trend with the overpotential. Moreover, the highest electroactivity of Ir2Pr is attributed to the improved electron transfer by 4f orbitals and the suitable binding strength of intermediates. Herein, a fundamental understanding of the lanthanide–electrochemical performance relationship is provided and will also inspire the rational design of efficient nanoscale RE alloy electrocatalysts.
Long‐term follow‐up of a patient with neonatal form of Gaucher disease
Authors: Gragnaniello Vincenza , Cazzorla Chiara , Gueraldi Daniela , Loro Christian , Massa Pamela , Puma Andrea , Cananzi Mara , Salviati Leonardo , Burlina Alessandro P. , Burlina Alberto B.
Published: April 2023

Gaucher disease is the most common of the lysosomal storage diseases. It presents a wide phenotypic continuum, in which one may identify the classically described phenotypes, including type 1 form with visceral involvement, type 2 acute neuropathic early‐infantile form, and type 3 subacute neuronopathic form. At the most severe end there is the perinatal form with onset in utero or during the neonatal period. The very few reported cases of neonatal onset Gaucher disease presented high and early mortality, due to neurological or visceral involvement, including liver failure. We report our experience treating a patient with the neonatal form of Gaucher disease who presented at birth with thrombocytopenia, hepatosplenomegaly and cholestasis. Despite early enzyme replacement therapy, liver disease was progressive. Liver biopsy showed hepatocellular giant‐cell transformation, a nonspecific finding consistent with inflammation. The lack of response to enzyme replacement therapy and the microscopic findings suggested that mechanisms apart from substrate accumulation and Gaucher cells may play a role in the hepatic pathogenesis in Gaucher disease. An attempt to use corticosteroids at the age of 3 months resulted in a dramatic improvement in liver function and resulted in long‐term survival. The patient is alive and 2 years old at this writing. Our case suggests that inflammatory processes may be important in the early pathogenesis of Gaucher disease and that early use of corticosteroids may open the way to a new therapeutic approach.
The range of publications on arthrogryposis multiplex congenita from 1995 to 2022—A scoping review
Authors: Hermansen My Vuong , Wekre Lena Lande , Lidal Ingeborg B.
Published: April 2023

Arthrogryposis multiplex congenita (AMC) is defined as “a group of congenital conditions characterized by joint contractures in two or more body areas.” Given its heterogeneity, the definition of AMC has changed multiple times. This scoping review provides an overview of how AMC is defined in scientific publications, on existing knowledge and trends regarding the concept of AMC. Our review illuminates possible knowledge gaps and provides directions for future research. A scoping review was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta‐Analyses extension for Scoping Reviews guidelines. Quantitative studies on AMC from 1995 to date were included. We summarized information about definitions/descriptions of AMC, study objectives, study designs, methods, funding, and involvement of patient organizations. A total of 2729 references were screened, and 141 articles fulfilled our inclusion criteria. Our scoping revealed that the majority of publications were cross‐sectional or retrospective studies of children and young people, commonly about orthopedic management. Explicit or good definitions of AMC were provided in 86% of the cases. Recent publications on AMC mostly used consensus‐based definitions. The research gaps were primarily related to adults, aging, etiology, and new medical treatment, in addition to implications on daily life.
High‐Current Capable and Non‐Flammable Protic Organic Electrolyte for Rechargeable Zn Batteries
Authors: Raza Bareera , Zhang Yu , Chen Jiahang , Shamraiz Umair , Zhang Yang , Naveed Ahmad , Wang Jiulin
Published: April 2023

Wiederaufladbare Zinkbatterien (RZBs) gelten aufgrund ihrer zahlreichen Vorteile als potente Konkurrenten für elektrochemische Geräte der nächsten Generation. Dennoch können herkömmliche wässrige Elektrolyte aufgrund der komplexen Reaktionskinetik in wässrigen Systemen durch schnellen Kapazitätsabfall und schlechte Coulomb′sche Effizienz (CE) ernsthafte Gefahren für den langfristigen Batteriebetrieb verursachen. Wir haben hier die neuartige Verwendung des protischen Amid‐Lösungsmittels N‐Methylformamid (NMF) als Zinkbatterie‐Elektrolyt vorgeschlagen, dass eine hohe Dielektrizitätskonstante und einen hohen Flammpunkt besitzt, um gleichzeitig eine schnelle Kinetik und Batteriesicherheit zu fördern. Die dendritenfreie und körnige Zn‐Abscheidung im Zn‐NMF‐Elektrolyten gewährleistet eine ultralange Lebensdauer von 2000 Stunden bei 2.0 mA cm−2/2.0 mAh cm−2, ein hohes CE von 99.57 %, ein breites elektrochemisches Fenster (≈3.43 V vs. Zn2+/Zn) und eine hervorragende Haltbarkeit bis zu 10.0 mAh cm−2. Diese Arbeit wirft ein Licht auf die effiziente Leistung des protischen nichtwässrigen Elektrolyten, der neue Möglichkeiten zur Förderung sicherer und energiedichter RZBs eröffnen wird.
Strong, Supertough and Self‐Healing Biomimetic Layered Nanocomposites Enabled by Reversible Interfacial Polymer Chain Sliding
Authors: Wang Yuyan , Shu Rui , Zhang Xinxing
Published: April 2023

Despite the remarkable progress in ultrastrong mechanical laminate materials, the simultaneous achievement of toughness, stretchability and self‐healing properties in biomimetic layered nanocomposites remains a great challenge due to the intrinsic limitations of their hard essences and lack of effective stress transfer at the organic‐inorganic fragile boundary. Here, an ultratough nanocomposite laminate is prepared by constructing chain‐sliding cross‐linking at the interface between sulfonated graphene nanosheets and polyurethane layers based on the ring molecules sliding on the linear polymer chains to release stresses. Unlike traditional supramolecular bonding toughening with limited sliding spacing, our strategy enables interfacial molecular chains reversible slippage when the inorganic nanosheets bear stretching force, providing sufficient interlayer spatial distance for relative sliding to dissipate more energy. The resulting laminates exhibit strong strength (22.33 MPa), supertoughness (219.08 MJ m−3), ultrahigh stretchability (>1900 %) and self‐healing ability (99.7 %), which far surpass most of reported synthetic and natural laminate materials. Moreover, the fabricated proof‐of‐concept electronic skin shows excellent flexibility, sensitivity and healability for human physiological signals monitoring. This strategy breaks through the challenge that traditional layered nanocomposites are intrinsically stiff and opens up the functional application of layered nanocomposites in flexible devices.
Infrared spectroscopy for ploidy estimation: An example in two species of Veronica using fresh and herbarium specimens
Authors: Buono Daniele , Albach Dirk C.
Published: April 2023

Premise

Polyploidy has become a central factor in plant evolutionary biological research in recent decades. Methods such as flow cytometry have revealed the widespread occurrence of polyploidy; however, its inference relies on expensive lab equipment and is largely restricted to fresh or recently dried material.

Methods

Here, we assess the applicability of infrared spectroscopy to infer ploidy in two related species of Veronica (Plantaginaceae). Infrared spectroscopy relies on differences in the absorbance of tissues, which could be affected by primary and secondary metabolites related to polyploidy. We sampled 33 living plants from the greenhouse and 74 herbarium specimens with ploidy known through flow cytometrical measurements and analyzed the resulting spectra using discriminant analysis of principal components (DAPC) and neural network (NNET) classifiers.

Results

Living material of both species combined was classified with 70% (DAPC) to 75% (NNET) accuracy, whereas herbarium material was classified with 84% (DAPC) to 85% (NNET) accuracy. Analyzing both species separately resulted in less clear results.

Discussion

Infrared spectroscopy is quite reliable but is not a certain method for assessing intraspecific ploidy level differences in two species of Veronica. More accurate inferences rely on large training data sets and herbarium material. This study demonstrates an important way to expand the field of polyploid research to herbaria.
Comparative Effectiveness of Rituximab‐ Versus Cyclophosphamide‐Based Remission Induction Strategies in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis for the Risk of Kidney Failure and Mortality
Authors: Wallace Zachary S. , Fu Xiaoqing , Cook Claire , Ahola Catherine , Williams Zachary , Doliner Brett , Hanberg Jennifer S. , Stone John H. , Zhang Yuqing , Choi Hyon K.
Published: April 2023

Objective

To compare rituximab‐ versus cyclophosphamide‐based remission induction strategies for the long‐term risks of kidney failure and death in antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) in a real‐world cohort.

Methods

We performed a cohort study using the Mass General Brigham AAV Cohort, which includes proteinase 3–ANCA+ and myeloperoxidase (MPO)‐ANCA+ AAV patients diagnosed from January 1, 2002 to December 31, 2019. We included cases in which the initial remission induction strategy was based either on rituximab or cyclophosphamide. The primary outcome was the composite outcome of kidney failure or death. We used multivariable Cox proportional hazards models and propensity score–matched analyses to assess the association of rituximab‐ versus cyclophosphamide‐based treatment strategies with the composite outcome of kidney failure or death.

Results

Of 595 included patients, 352 patients (~60%) received rituximab‐based and 243 patients (~40%) received cyclophosphamide‐based regimens. The mean age was 61 years, 58% of patients were female, 70% of patients were MPO‐ANCA+, and 69% of patients had renal involvement (median estimated glomerular filtration rate 37.3 ml/minute/1.73 m2). There were 133 events at 5 years, and the incidence rates in rituximab‐ and cyclophosphamide‐based regimens were 6.8 and 6.1 per 100 person‐years, respectively. The risk of kidney failure or death was similar in both groups in multivariable‐adjusted analyses (hazard ratio [HR] 1.03 [95% confidence interval (95% CI) 0.55–1.93]) and in propensity score–matched analyses (HR 1.05 [95% CI 0.55–1.99]) at 5 years. Our findings were similar when outcomes were assessed at 1 and 2 years as well as in subgroups stratified according to renal involvement and severity as well as major organ involvement.

Conclusion

Rituximab‐ and cyclophosphamide‐based remission induction strategies for AAV are associated with similar risks of kidney failure and death.
Higher Genetic Risk Loads Confer More Diverse Manifestations and Higher Risk of Lupus Nephritis in Systemic Lupus Erythematosus
Authors: Kwon Young‐Chang , Ha Eunji , Kwon Hyuk‐Hee , Park Dae Jin , Shin Jung‐Min , Joo Young Bin , Chung Won Tae , Yoo Dae‐Hyun , Lee Hye‐Soon , Kim Kwangwoo , Bae Sang‐Cheol , Bang So‐Young
Published: April 2023

Objective

Systemic lupus erythematosus (SLE) is a highly heritable complex disorder with heterogeneous clinical manifestations. In this study, we aimed to identify the genetic risk load using clinical and serological manifestations in SLE patients.

Methods

We genotyped a total of 1,655 Korean patients with SLE (n = 1,243 as a discovery set and n = 412 as a replication set) using a customized genome‐wide single‐nucleotide polymorphism (SNP) array, KoreanChip. A weighted genetic risk score (wGRS) for an individual was calculated from 112 well‐validated non‐HLA SNPs and HLA haplotypes of SLE‐risk loci. We analyzed associations between individual wGRS and clinical SLE subphenotypes and autoantibodies using multivariable linear or logistic regression adjusted by onset age, sex, and disease duration.

Results

Childhood‐onset SLE (<16 years) conferred the highest genetic risk compared with adult‐onset (16–50 years) or late‐onset (>50 years) SLE (P = 6.8 × 10−6). High wGRS significantly increased associations with SLE manifestations, regardless of onset age, sex, and disease duration. Individual wGRS significantly correlated positively with more clinical American College of Rheumatology criteria (β = 0.143, P = 1.8 × 10−6). Subphenotype analysis revealed significant associations between the highest and lowest wGRS quartile with risk of renal disorder (hazard ratio [HR] 1.74, P = 2.2 × 10−8) and anti–Sm antibody production (HR 1.85, P = 2.8 × 10−5). Higher wGRS markedly modulated the pathogenesis of proliferative and membranous lupus nephritis class III or IV (HR 1.98, P = 1.6 × 10−5) and class V (HR 2.79, P = 1.0 × 10−3), but especially lupus nephritis class V in anti–Sm‐positive SLE (area under the curve 0.68, P = 1.8 × 10−4).

Conclusion

Patients with SLE and high wGRS tended to have earlier age of SLE onset, higher anti–Sm antibody positivity, and more diverse clinical phenotypes. Genetic profiling may predict high risk for lupus nephritis and a diverse clinical course in SLE patients.
Mechanoresponsive Fluorescence On‐off Switching of Two‐component Emitters Composed of Mechanochromically Luminescent Dyes and Non‐emissive Pigments
Authors: Kubota Rikuto , Takahashi Shohei , Nagai Sayaka , Ito Suguru
Published: April 2023

Organic emitters capable of changing their luminescence properties in response to mechanical stimuli have recently attracted considerable attention. While mechanoresponsive switching of luminescence color has been widely investigated, there are only a limited examples regarding the on‐off luminescence intensity switching by mechanical stimulation. Consequently, rational design guidelines for mechanoresponsive switching of luminescence intensity have not been established. Herein, on‐off luminescence switching has been achieved by two‐component organic emitters composed of phenanthroimidazolylbenzothiadiazoles, which exhibit mechanochromic luminescence (MCL), and non‐emissive pigments. In these two‐component emitters, the emission color can be tuned by changing the MCL dye, and the apparent color under room light can be modulated by changing the non‐emissive pigment. Moreover, we have demonstrated the encryption and decryption of luminescent displays by using the two‐component emitter. The present two‐component strategy is expected to serve as a useful method for developing advanced mechanoresponsive luminescent materials.
1,3‐Dipolar Cycloaddition of 3‐Chromonyl‐Substituted Glycine Imino Esters with Arylidenes and in situ Diastereodivergent via Retrocycloaddition
Authors: Radwan Mohammed F. , Elboray Elghareeb E. , Dardeer Hemat M. , Kobayashi Yusuke , Furuta Takumi , Hamada Shohei , Dohi Toshifumi , Aly Moustafa F.
Published: April 2023

1,3‐Dipolar cycloaddition through in situ generation of azomethine ylide provides a straightforward and critically important sustainable approach for access to diverse pyrrolidine chemical space. Herein, we developed a metal‐free AcOH‐activated 1,3‐dipolar cycloaddition protocol that permits the synthesis of uncommon pyrrolidine cycloadducts with excellent diastereoselectivity. The challenging substrates of 3‐formylchromone, glycine ester.HCl and arylidene dipolarophile were reacted in the presence of AcONa, which played a dual role as a base and AcOH source, to deliver firstly endo‐cycloadduct. Under prolonged reaction time at room temperature or heating; the endo‐adduct underwent diastereodivergent via a sequence of retro‐cycloaddition, stereomutation of the generated syn‐dipole into anti‐dipole and recycloaddition; to furnish the scarcely known exo′‐cycloadduct with high diastereodivergency. The reaction worked well with a broad range of substrates and the stereochemistry of the obtained cycloadducts was determined without ambiguity using NMR‐ and X‐ray analysis. Experimental and theoretical DFT calculation studies were performed to support the proposed reaction mechanism and elucidate the key role of AcOH in the process which seems more beneficial than other transition metal‐catalyzed processes.
Preclinical development of a novel Group B Streptococcus (GBS) vaccine candidate for maternal immunization based upon the alpha‐like protein family of GBS surface proteins (Alp)
Authors: Banks Christopher , Lindbom Bengt J. , Kitson Geoff , Darsley Michael , Fischer Per B.
Published: April 2023

A novel Group B Streptococcus (GBS) vaccine, based upon the GBS alpha‐like surface proteins, is being developed by MinervaX for administration to pregnant women. The vaccine is intended to generate antibodies (IgG) capable of crossing the placenta, in order to passively immunize the baby and provide protection in utero and up to 3 months after birth. An initial vaccine candidate, GBS‐NN (based on the N‐terminal domains of Rib and AlphaC surface proteins) was replaced, due to insufficient cross‐reactivity with the two other N‐terminal proteins (Alp1 and Alp2/3), by a modified vaccine candidate designated GBS‐NN/NN2 that included all four AlpNs. Preclinical studies raised no safety concerns and the subsequent Phase I clinical trial demonstrated that the vaccine was well tolerated and strongly immunogenic. As the vaccine is intended for use during pregnancy for maternal immunization, an embryofetal study in rats and a fertility and embryofetal study in rabbits were performed, in both cases using GBS‐NN/NN2. Vaccination of female rats or rabbits did not adversely affect embryofetal development or survival in either species, or mating or fertility in rabbits. In both studies, the pregnant animals developed immune responses to GBS‐NN and GBS‐NN2 proteins and concentrations of antibodies to both fusion proteins were detected in the fetuses and in the amniotic fluid. Data generated during these reproductive studies indicated a suitable safety margin (approximately 40‐fold clinical dose) considered appropriate to support a subsequent human trial of GBS‐NN/NN2 administered in the second and third trimesters of pregnancy.
Chromatographic separation of tiropramide hydrochloride and its degradation products along with their structural characterization using liquid chromatography quadrupole time‐of‐flight tandem mass spectrometry and nuclear magnetic resonance
Authors: Tidke Manik , Golla Vijaya Madhyanapu , Kushwah Bhoopendra Singh , Naik Dhanavath Dattu , Gananadhamu Samanthula
Published: April 2023

Tiropramide HCl, a widely used antispasmodic drug, was subjected to various stress conditions (hydrolytic, oxidative, photolytic and thermal) per International Council for Harmonization guidelines in the present work. However, there were no comprehensive degradation studies reported on the drug. Therefore, forced degradation studies of tiropramide HCl were carried out to establish the degradation profile and the storage conditions to maintain its quality attributes during the shelf life and usage. A selective HPLC method was developed to separate the drug and its degradation products (DPs) using Agilent C18 column (250 × 4.6 mm; 5 μm). The mobile phase of 10 mM ammonium formate at pH 3.6 (solvent A) and methanol (solvent B) with gradient elution at a flow rate of 1.00 ml/min was used. Tiropramide was found to be susceptible to acidic and basic hydrolytic exposures as well as oxidative stress conditions in the solution state. This drug was found to be stable under neutral, thermal and photolytic conditions in both solutions and the solid state. Five DPs were detected under different stress conditions. The mass spectrometric fragmentation pattern of tiropramide and its DPs was extensively studied using liquid chromatography quadrupole time‐of‐flight tandem mass spectrometry for their structural characterization. The position of the oxygen atom in the N‐oxide DP was confirmed by NMR studies. The knowledge gained by these studies was used to predict drug degradation profiles, which help analyse any impurities in the dosage form.
A rare cutaneous manifestation of immune checkpoint inhibitor therapy
Authors: Cherneskie John , Tuan Alyssa , Corey Zachary , Polimera Hyma
Published: April 2023

Leukocytoclastic vasculitis can be an uncommon and/or underreported adverse event of immune checkpoint inhibitor therapy, an established cancer treatment option. Differentiation among other cutaneous manifestations of adverse medication reactions—such as Stevens–Johnson syndrome, erythema multiforme, and drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome—is crucial for guiding management.
Posterior reversible encephalopathy syndrome in SARS‐CoV‐2 infection: A case report and review of literature
Authors: Ziaee Mahsa , Saeedi Maryam , Rohani Mohammad , Mehrpour Masoud , Haghi Ashtiani Bahram , Zamani Babak , Akhoundi Fahimeh Haji , Salahi Khalaf Misagh , Mirmoeeni Seyyedmohammadsadeq , Azari Jafari Amirhossein , Shateri Zahra
Published: April 2023

Consider PRES in SARS‐CoV‐2 infected patients who develop encephalopathy, seizures or impaired vision; especially if the disease is complicated by respiratory distress and need for mechanical ventilation.
Construction of Pd‐Co‐Doped CdS Heterojunctions as Efficient Platforms in Photocatalysis
Authors: Paraschoudi Eirini N. , Bairamis Feidias , Sygellou Lamprini , Andrikopoulos Konstantinos S. , Konstantinou Ioannis , Tasis Dimitrios
Published: April 2023

In this work, we present the structural, optical and photocatalytic properties of CdS semiconducting nanostructures, doped with palladium‐ and cobalt‐based species. XRD analysis, corroborated by Raman and XPS, demonstrated the growth of CdS crystallites in the hexagonal structure, whereas solvothermal conversion of neat precursor metal salts resulted in the formation of metallic Pd and cobalt oxide, respectively. Scanning electron microscopy imaging certified the dendritic structure of hybrids, especially in the case where CdS was grown in the presence of either palladium‐ or cobalt‐based nanoparticles. XPS surface analysis revealed that a major fraction of metallic Pd nanoparticles was converted to PdO during the in situ growth of CdS nanoparticles. The oxidation of Pd nanoparticles could be ascribed to chemisorption of oxygen phases onto the metal surface. The presence of cocatalyst nanoparticles resulted in an appreciable shift of the absorption edge of the ternary hybrids by about 50 nm. The optimized hybrid was found to photodegrade Orange G dye almost quantitatively within 2 h, by simulated solar light irradiation. Scavenging experiments revealed that hydroxy radicals were the main transient intermediate, leading to the oxidative degradation of the dye.
Dioxygen Binding Is Controlled by the Protein Environment in Non‐heme FeII and 2‐Oxoglutarate Oxygenases: A Study on Histone Demethylase PHF8 and an Ethylene‐Forming Enzyme
Authors: Chaturvedi Shobhit S. , Thomas Midhun George , Bathir Jaber Sathik Rifayee Simahudeen , White Walter , Wildey Jon , Warner Cait , Schofield Christopher J. , Hu Jian , Hausinger Robert P. , Karabencheva‐Christova Tatayana G. , Christov Christo Z.
Published: April 2023

Invited for the cover of this issue are Christo Z. Christov and co‐workers at Michigan Technological University, University of Oxford, and Michigan State University. The image depicts the oxygen diffusion channel in class 7 histone demethylase (PHF8) and ethylene‐forming enzyme (EFE) and changes in the enzymes’ conformations upon binding. Read the full text of the article at 10.1002/chem.202300138.
Bioactive Phenolate Salts: Thymol Salts
Authors: Reddy Pulikanti Guruprasad , Domb Abraham J.
Published: April 2023

Phenolate salts of bioactive agents have been reported only scarcely. This is the first report on the formation and characterization of thymol phenolate salts as representatives of phenol‐containing bioactive molecules. Thymol has been used in medicine and agriculture for decades owing to its excellent therapeutic properties. However, in light of its poor aqueous solubility, thermal instability, and especially its high chemical volatility, the utility of thymol is hampered. The present work focuses on tuning the physicochemical properties of thymol by modifying its chemical structure through salt formation. In this context, a series of metal (Na, K, Li, Cu, and Zn) and ammonium (tetrabutylammonium and choline) salts of thymol were synthesized and characterized using IR, NMR, CHN elemental analysis, and DSC analyses. The molecular formulae of thymol salts were determined based on CHN analysis and thymol quantification studies from UV‐Vis spectrometric analysis. In most cases, the thymol phenolate was prepared as a 1 : 1 molar ratio with metal/ammonium ion. Only the Cu salt of thymol was isolated at a ratio of two phenolate units per copper ion. Most of the synthesized thymol salts were found to have increased thermal stability relative to thymol. The physicochemical properties such as solubility, thermal stability, and evaporation rate of thymol salts were thoroughly studied in comparison with thymol. The in vitro release studies of Cu from the copper salt of thymol is pH‐dependent: rapid release of copper was observed in the lower pH release medium (100 % release at pH 1 for 12 days) and the rates of release were slower at higher pH values (5 % release at pH 2, and <1 % release at pH 4, 6, 8, and 10) over a period of about three weeks.
Trends in health care spending on kidney cancer in the United States, 1996–2016
Authors: Takemura Kosuke , Ahmed Newaz Shubidito , Stukalin Igor , Gupta Mehul , Ma Christopher , Heng Daniel Y. C.
Published: April 2023

Background

Paradigm shifts in kidney cancer management have led to higher health care spending. Here, total and per capita health care spending and primary drivers of change in health expenditures for kidney cancer in the United States between 1996 and 2016 are estimated.

Methods

Public databases developed by the Institute for Health Metrics and Evaluation for the Disease Expenditure Project were used. The prevalence of kidney cancer was estimated from the Global Burden of Disease Study. Changes in health care spending on kidney cancer were assessed by joinpoint regression and expressed as annual percent changes (APCs).

Results

In 2016, total health care spending on kidney cancer was $3.42 billion (95% CI, $2.91 billion to $3.89 billion) compared with $1.18 billion (95% CI, $1.07 billion to $1.31 billion) in 1996. Per capita spending had two inflection points in 2005 and 2008, close to the approval years of targeted therapies, which corresponded to APCs of +2.9% (95% CI, +2.3% to +3.6%; p < .001) per year, 1996–2005; +9.2% (95% CI, +3.4% to +15.2%; p = .004) per year, 2005–2008; and +3.1% (95% CI, +2.2% to +3.9%; p < .001) per year, 2008–2016. Inpatient care was the largest contributor to health expenditures, which accounted for $1.56 billion (95% CI, $1.19 billion to $1.95 billion) in 2016. Price and intensity of care was the primary driver of increased health expenditures, whereas service utilization was the primary driver of reduced health expenditures.

Conclusions

Prevalence‐adjusted health care spending on kidney cancer continues to rise in the United States, which is primarily attributable to inpatient care and driven by the price and intensity of care over time.
Hemodynamic investigation of a novel rotary displacement blood pump for extracorporeal membrane oxygenation
Authors: Xue Qingxin , Ren Xiaoyu , Gao Bin , Li Shu , Song Zhiming , Ding Jinli , Chang Yu
Published: April 2023

Extracorporeal membrane oxygenation (ECMO) is a life support system used in the treatment of severe respiratory and circulatory failure. High shear stress caused by the high rotational speed of centrifugal blood pumps can cause hemolysis and platelet activation, which are among the major factors leading to the complications of the ECMO system. In this study, a novel blood pump named rotary displacement blood pump (RDBP), which can considerably reduce rotational speed and shear stress while ensuring the normal pressure flow relationship, was proposed. We employed computational fluid dynamics (CFD) analysis to investigate the performance of RDBP under adult ECMO support operating conditions (5 L/min with 350 mmHg). The efficiency and H‐Q curves of the RDBP were calculated to evaluate its hydraulic performance, and pressure, flow patterns, and shear stress distribution were analyzed to estimate the hemodynamic characteristics in the pump. In addition, the modified index of hemolysis (MIH) was calculated for the RDBP based on a Eulerian approach. The hydraulic efficiency of the RDBP was 47.28%. The velocity distribution of flow field in the pump was relatively uniform. Most of the liquid (more than 75%) in the pump was exposed to low scale shear stress (<1 Pa), which was close to normal physiological conditions. The gap area was the main distribution location of high scale shear stress. The high wall shear stress (>9 Pa) volume fraction of the RDBP was small and located in the boundary areas between the rotor's edge and the housing. The MIH value of the RDBP was 9.87 ± 0.93 (mean ± SD). The RDBP can achieve better hydraulic efficiency and hemodynamic performance at lower rotational speed. The design of this novel pump is expected to provide a new direction for developing a blood pump for ECMO.
Second Generation of Cata‐Annulated Azaacene Bisimides: Towards Electron‐Accepting Materials
Authors: Hippchen Nikolai , Heinzel Elena , Zhang Cathy K. , Jäger Patrick , Elter Maximilian , Ludwig Philipp , Rominger Frank , Freudenberg Jan , Cao Dennis D. , Bunz Uwe H. F.
Published: April 2023

This work presents the 2nd generation of cata‐annulated azaacene bisimides with increased electron affinities (up to −4.38 eV) compared to their consaguine conventional azaacenes. These compounds were synthesized via Buchwald–Hartwig coupling followed by oxidation with MnO2. Crystal structure engineering through variation of the bisimide substituents furnished crystalline derivatives suitable for proof of concept organic field effect transistors with electron mobilities up to 2.2×10−4 cm2(Vs)−1. Moreover, we were able to characterize the charge carrying species, the radical anion, using electron paramagnetic resonance and absorption measurements.
IP address allocation protocols in vehicular ad hoc networks
Authors: Ajaz Farhana , Naseem Mohd , Ahamad Gulfam
Published: April 2023

In vehicular ad hoc networks (VANETs), communication takes place between vehicles to vehicles, the vehicles to the road side units, and vice‐versa. The basic purpose of these communications is to share and exchange tremendous amount of data and information. For efficient information sharing, a systematic and structured connection establishment algorithm is needed. In VANETs, each connected node of the network need to be assigned a unique address. Hence, an algorithm is needed for the proper assignment of unique address to all nodes in the network. This paper explains different types of IP address protocols in VANETs. We have also explained advantage and disadvantage of existing IP address allocation protocols in VANETs.
Involvement of matrix metalloproteinase 1 and urokinase‐type plasminogen activator in the PKCα‐p38 MAPK pathway‐mediated progression of human liver cancer cells
Authors: Ye Je‐Chiuan , Hsieh Yih‐Shou , Chen Pei‐Ni , Liu Jer‐Yuh , Hsieh Yi‐Hsien
Published: April 2023

Our previous studies have shown that the plasminogen activator (PA) and matrix metalloproteinases (MMPs) proteinase systems were highly expressed in highly malignant liver cancer cells and regulated by PKCα. This study investigates whether the PKCα regulation of PA and MMPs systems is conducted through p38 mitogen‐activated protein kinase (MAPK) signaling and the pathway is responsible for promoting cell progression. We found that the expressions of p38 MAPK in both highly malignant HA22T/VGH and SK‐Hep‐1 liver cancer cells were higher than that in other lower malignancy liver cancer cells. Since PKCα activates p38 MAPK in progression of liver cancer, we suspected the PKCα/p38 MAPK signaling pathway to be involved in the regulation of MMPs and PA systems. When SK‐Hep‐1 cells were treated with SB203580 or DN‐p38, only MMP‐1 and u‐PA mRNA expressions decreased. The p38 MAPK inhibition also decreased the cell migration and invasion. In addition, the mRNA decay assays showed that the higher expressions of MMP‐1 and u‐PA mRNA in SK‐Hep‐1 cells were due to the alteration of mRNA stability by p38 MAPK inhibition. Zymography of SK‐Hep‐1 cells treated with siPKCα vector also showed the decrease of the activity of MMP‐1 and u‐PA and confirmed changes in mRNA level. Furthermore, only the transfection of MKK6 to the siPKCα‐treated SK‐Hep‐1 stable clone cell restored the attenuation of MMP‐1 and u‐PA expressions. The treatment of SK‐Hep‐1 cells with either inhibitor of MMP‐1 or u‐PA reduced migration, and the reduction was enhanced with both inhibitors. In addition, tumorigenesis was also reduced with both inhibitors. These data suggest a novel finding that MMP‐1 and u‐PA are critical components in PKCα/MKK6/p38 MAPK signaling pathway which mediates liver cancer cell progression, and that the targeting of both genes may be a viable approach in liver cancer treatment.
Association of sleep patterns and cardiovascular disease risk is modified by glucose tolerance status
Authors: Wang Bin , Zhang Haojie , Sun Ying , Tan Xiao , Zhang Jihui , Wang Ningjian , Lu Yingli
Published: April 2023

Aims

To investigate whether the association between sleep patterns and cardiovascular disease (CVD) risk differs according to glucose tolerance status.

Materials and Methods

This prospective study included 358,805 participants initially free of CVD from the UK Biobank. We created a sleep score based on five sleep factors (sleep duration, chronotype, insomnia, snoring, and daytime sleepiness) with one point for each unhealthy factor. Cox proportional hazards models were used to examine the association between sleep and incident CVD, including coronary heart disease (CHD) and stroke, according to normal glucose tolerance (NGT), prediabetes, and diabetes.

Results

During a median follow‐up of 12.4 years, 29,663 incident CVD events were documented. There was a significant interaction between sleep score and glucose tolerance status on CVD (P for interaction = 0.002). Each 1 point increment in sleep score was associated with a 7% (95% confidence interval 6%–9%), 11% (8%–14%), and 13% (9%–17%) higher risk of CVD among participants with NGT, prediabetes, and diabetes, respectively. Similar interaction patterns were observed for CHD and stroke. Among the individual sleep factors, sleep duration and insomnia significantly interacted with glucose tolerance status on CVD outcomes (all P for interaction <0.05). All five unhealthy sleep factors accounted for 14.2% (8.7%–19.8%), 19.5% (7.4%–31.0%), and 25.1% (9.7%–39.3%) of incident CVD cases among participants with NGT, prediabetes, and diabetes, respectively.

Conclusions

The CVD risk associated with a poor sleep pattern was exacerbated across glucose intolerance status. Our findings emphasise the importance of integrating sleep management into a lifestyle modification programme, particularly in people with prediabetes or diabetes.