bluuebunny/crossref_metadata_2025 huggingface dataset:
Electron Transfer from Haem to the Di‐Iron Ferroxidase Centre in Bacterioferritin
Authors: Pullin Jacob , Bradley Justin M. , Moore Geoffrey R. , Le Brun Nick E. , Wilson Michael T. , Svistunenko Dimitri A.
Published: January 2021

The iron redox cycle in ferritins is not completely understood. Bacterioferritins are distinct from other ferritins in that they contain haem groups. It is acknowledged that the two iron motifs in bacterioferritins, the di‐nuclear ferroxidase centre and the haem B group, play key roles in two opposing processes, iron sequestration and iron mobilisation, respectively, and the two redox processes are independent. Herein, we show that in Escherichia coli bacterioferritin, there is an electron transfer pathway from the haem to the ferroxidase centre suggesting a new role(s) haem might play in bacterioferritins.
Aramid pulp treated with imidazolium ionic liquids as a filler in rigid polyurethane bio‐foams
Authors: Kerche Eduardo Fischer , da Silva Vinícius Demétrio , da Silveira Jankee Gabriela , Schrekker Henri Stephan , de Avila Delucis Rafael , Irulappasamy Siva , Amico Sandro Campos
Published: January 2021

This article reports an aramid pulp (AP) treated with two ionic liquids (IL), namely 1‐n‐butyl‐3‐methylimidazolium chloride (C4.Cl) and 1‐carboxymethyl‐3‐methylimidazolium chloride (HO2C), and its use as a filler in reinforced rigid polyurethane foams (RPUF). The RPUF were incorporated with the treated AP at three weight fractions (c.a. 0.1, 0.5, and 1.0 wt%) and were produced by the free rising method. The results showed that the studied IL promoted a better interaction between the AP and the RPUF system, which increased the overall reactivity, imparting a higher cell anisotropy. This also yielded a positive effect in mechanical properties and thermal stability of the RPUF. Compared to the neat RPUF, outstanding increases of approximately 50 and 20% were achieved in compressive modulus and strength, respectively. In all, the use of IL promoted increased compatibility between matrix and reinforcement, especially that HO2C IL.
Addressing hard‐to‐reach populations for achieving malaria elimination in the Asia Pacific Malaria Elimination Network countries
Authors: Wangdi Kinley , Pasaribu Ayodhia Pitaloka , Clements Archie C.A.
Published: January 2021

Member countries of the Asia Pacific Malaria Elimination Network are pursuing the regional goal of malaria elimination by 2030. The countries are in different phases of malaria elimination, but most have demonstrated success in shrinking the malaria map in the region. However, continued transmission in hard‐to‐reach populations, including border and forest malaria, remains an important challenge. In this article, we review strategies for improving intervention coverage in hard‐to‐reach populations. Currently available preventive measures, including long‐lasting insecticidal nets and long‐lasting insecticidal hammocks, and prompt diagnosis and treatment need to be expanded to hard‐to‐reach populations. This can be done through mobile malaria clinics, village volunteer malaria workers and screening posts. Malaria surveillance in the hard‐to‐reach areas can be enhanced through tools such as spatial decision support systems. Policy changes by the malaria programs will be required for implementing the strategies outlined in this article. However, strategies or tools may be suitable for some population groups but difficult to implement in other groups.
Comprehensive insights into the formation of metabolites of the ghrelin mimetics capromorelin, macimorelin and tabimorelin as potential markers for doping control purposes
Authors: Lange Tobias , Thomas Andreas , Görgens Christian , Bidlingmaier Martin , Schilbach Katharina , Fichant Eric , Delahaut Philippe , Thevis Mario
Published: January 2021

Analytical methods to determine the potential misuse of the ghrelin mimetics capromorelin (CP‐424,391), macimorelin (macrilen, EP‐01572) and tabimorelin (NN703) in sports were developed. Therefore, different extraction strategies, i.e. solid‐phase extraction, protein precipitation, as well as a “dilute‐and‐inject” approach, from urine and EDTA–plasma were assessed and comprehensive in vitro/in vivo experiments were conducted, enabling the identification of reliable target analytes by means of high resolution mass spectrometry. The drugs’ biotransformation led to the preliminary identification of 51 metabolites of capromorelin, 12 metabolites of macimorelin and 13 metabolites of tabimorelin. Seven major metabolites detected in rat urine samples collected post‐administration of 0.5–1.0 mg of a single oral dose underwent in‐depth characterization, facilitating their implementation into future confirmatory test methods. In particular, two macimorelin metabolites exhibiting considerable abundances in post‐administration rat urine samples were detected, which might contribute to an improved sensitivity, specificity, and detection window in case of human sports drug testing programs. Further, the intact drugs were implemented into World Anti‐Doping Agency‐compliant initial testing (limits of detection 0.02–0.60 ng/ml) and confirmation procedures (limits of identification 0.18–0.89 ng/ml) for human urine and blood matrices. The obtained results allow extension of the test spectrum of doping agents in multitarget screening assays for growth hormone‐releasing factors from human urine.
Retropharyngeal edema secondary to superior vena cava syndrome revealing Behcet's disease
Authors: Maalej Firas , Achour Imen , Zaidi Anis , Thabet Wadii , Chaabouni Mohamed Amine , Hammami Bouthaina , Ben Mahfoudh Kheireddine , Mnejja Malek , Charfeddine Ilhem
Published: January 2021

Retropharyngeal edema, uncommon in superior vena cava syndrome, can exceptionally represent the first manifestation of Behcet's disease, which should be taken into account in the differential diagnosis of this condition.
Photocatalytic Hydrogen Production by Stable CsPbBr3@PANI Nanoparticles in Aqueous Solution
Authors: Song Wentao , Wang Yiming , Wang Cheng , Wang Bing , Feng Jianyong , Luo Wenjun , Wu Congping , Yao Yingfang , Zou Zhigang
Published: January 2021

CsPbX3 (X=Cl, Br, I) nanocrystals (NCs) are considered as one of the most promising photocatalytic materials. Unfortunately, their environmental instability, especially the intrinsic water vulnerability, brought their applications major obstacles in the photosynthetic fields. To improve the stability for photocatalytic water splitting, we for the first time chose conductive polymer, polyaniline (PANI), as the encapsulating material to fabricate CsPbBr3@PANI nanoparticles (NPs) by photo‐polymerization method. After optimizing, the photocatalytic hydrogen production efficiency of CsPbBr3@PANI NPs reached 4.81 mmol/(h ⋅ g) and the catalytic lifetime achieved 120 hours. Our work that achieved the stable CsPbBr3@PANI NPs shed light on potential opportunity for catalytic application of CsPbBr3 NCs.
The Indigo Isomer Epindolidione as a Redox‐Active Bridging Ligand for Diruthenium Complexes
Authors: Kumari Maya , Bera Sudip Kumar , Blickle Svenja , Kaim Wolfgang , Lahiri Goutam Kumar
Published: January 2021

Epindolidione (H2L), a heteroatom‐modified analogue of tetracene and a structural isomer of indigo, forms dinuclear complexes with [RuX2]2+, X=bpy (2,2′‐bipyridine, [1]2+) or pap (2‐phenylazopyridine, [2]2+), in its doubly deprotonated bridging form μ‐L2−. The dications in compounds meso‐[1](ClO4)2 and meso‐[2](ClO4)2, [X2Ru(μ‐L)RuX2](ClO4)2, contain five‐membered chelate rings N‐C−C‐O‐RuII with π bridged metals at an intramolecular distance of 7.19 Å. Stepwise reversible oxidation and reduction is mainly ligand centered (oxidation: L2−; reduction: X), as deduced from EPR of one‐electron oxidized and reduced intermediates and from UV/Vis/NIR spectroelectrochemistry, supported by TD‐DFT calculation results. The results for [1](ClO4)2 and [2](ClO4)2 are qualitatively similar to the ones observed with the deprotonated indigo‐bridged isomers with their six‐membered chelate ring structures, confirming the suitability of both π systems for molecular electronics applications, low‐energy absorptions, and multiple electron transfers.
Donor–Acceptor Interactions Induced Interfacial Synthesis of an Ultrathin Fluoric 2D Polymer by Photochemical [2+2] Cycloaddition
Authors: Sun Qingzhu , Pan Qingyan , Ban Yanqi , Liu Hui , Fan Chunyan , Sun Lishui , Zhao Yingjie
Published: January 2021

Invited for the cover of this issue is the group of Prof. Dr. Yingjie Zhao at Qingdao University of Science and Technology. The image depicts the ultrathin two‐dimensional polymer reported in this work. Read the full text of the article at 10.1002/chem.202004797.
Self‐Assembling Catalytic Peptide Nanomaterials Capable of Highly Efficient Peroxidase Activity
Authors: Zozulia Oleksii , Marshall Liam R. , Kim Inhye , Kohn Eric M. , Korendovych Ivan V.
Published: January 2021

The self‐assembly of short peptides gives rise to versatile nanomaterials capable of promoting efficient catalysis. We have shown that short, seven‐residue peptides bind hemin to produce functional catalytic materials which display highly efficient peroxidation activity, reaching a catalytic efficiency of 3×105 m−1 s−1. Self‐assembly is essential for catalysis as non‐assembling controls show no activity. We have also observed peroxidase activity even in the absence of hemin, suggesting the potential to alter redox properties of substrates upon association with the assemblies. These results demonstrate the practical utility of self‐assembled peptides in various catalytic applications and further support the evolutionary link between amyloids and modern‐day enzymes.
Facile Construction of Carbon Dots Layer and Oxygen Vacancies Simultaneously onto TiO2 to Enhance Photoreduction Activity
Authors: Zhao Jingyu , Li Yaru , Na Ping
Published: January 2021

Main observation and conclusion

We reported a facile and green hydrothermal strategy to tailor the carbon dots layer (CDL) and oxygen vacancies (Vo) modified on TiO2, by using ascorbic acid as CDL precursor and Vo regulator. The amorphous CDL was uniformly coated on the surface of the as prepared CDL@TiO2–x composites by Ti‐O‐C bond. With the increase of carbon content, the amorphous CDL gradually became thicker, while the Vo concentration first increased and then decreased. 1.5 CDL@TiO2–x possessed the highest Vo concentration. With the decoration of CDL and Vo, the photoreduction properties of CDL@TiO2–x composites were significantly improved. Under simulated solar light and visible light, the reaction rates of 1.5 CDL@TiO2–x were 9.6 times and 216 times higher than that of pure TiO2, respectively. Interestingly, the results discovered that CDL and Vo influenced the properties of CDL@TiO2–x composites in different ways. The primary function of CDL was to improve the utilization of solar light, and the enhancement of the charge transfer ability was decided by Vo and CDL together. Our work provides a new strategy for the modification of TiO2 and sheds new light on the respective role of CDL and Vo when they coexist in the catalyst.
Naphthalimide‐Based Dyes as Photoinitiators under Visible Light Irradiation and their Applications: Photocomposite Synthesis, 3D printing and Polymerization in Water
Authors: Rahal Mahmoud , Mokbel Haifaa , Graff Bernadette , Pertici Vincent , Gigmes Didier , Toufaily Joumana , Hamieh Tayssir , Dumur Frédéric , Lalevée Jacques
Published: January 2021

In this work, six new fluorescent dyes derived from the naphthalimide scaffold (Napht1–Napht6) were synthesized and used as high‐performance photoinitiating systems (PISs) in two and three‐component systems (combined with iodonium salt (Iod) and/or an electron donor amine (such as N‐phenylglycine[NPG])) for the radical photopolymerization of acrylate and methacrylate monomers under visible light using a light‐emitting diode at 405 nm. Markedly, these dyes were never synthesized before. In fact, these PISs showed high initiation efficiency with both demonstrating high final reactive function conversions and high polymerization rates. A further interest of our study is to determine the effect of the different substituents (chromophoric group) on the naphthalimide function, concerning the efficiency of initiation of the free radical polymerization. In order to improve the mechanical properties of the obtained polymers, these derivatives were also tested for the photopolymerization of a blend of acrylate/epoxy monomers (TA/EPOX); these latter properties were characterized by traction tests. To demonstrate the initiation efficiency of these dyes, several methods and characterization techniques were used, including steady state photolysis, real‐time Fourier transform infrared spectroscopy, emission spectroscopy as well as cyclic voltammetry. In our study, these naphthalimides were used for the synthesis of photocomposites (one and multiple layers of glass fibres) using a UV@395 nm (4 W/cm2) conveyor, as well as in the preparation of 3D printed polymers. Markedly, one of the naphthalimide derivatives (Napht‐4) can be used as a new high‐performance water soluble photoinitiator for photopolymerization in water and hydrogel synthesis.
On the advanced integral equation theory description of dense Yukawa one‐component plasma liquids
Authors: Castello Federico Lucco , Tolias Panagiotis
Published: January 2021

Different advanced bridge function closures are utilized to investigate the structural and thermodynamic properties of dense Yukawa one‐component plasma liquids within the framework of integral equation theory. The isomorph‐based empirically modified hypernetted‐chain, the variational modified hypernetted‐chain, the Rogers–Young, and the Ballone–Pastore–Galli–Gazzillo approaches are compared at the level of thermodynamic properties, radial distribution functions, and bridge functions. The comparison, based on accuracy and computational speed, concludes that the two modified hypernetted‐chain approaches are superior and singles out the isomorph‐based variant as the most promising alternative to computer simulations of structural properties of dense Yukawa liquids. The possibility of further improvement through artificial crossover to exact asymptotic limits is studied.
Photoredox Allylation Reactions Mediated by Bismuth in Aqueous Conditions
Authors: Potenti Simone , Gualandi Andrea , Puggioli Alessio , Fermi Andrea , Bergamini Giacomo , Cozzi Pier Giorgio
Published: January 2021

Organometallic allylic reagents are widely used in the construction of C−C bonds by Barbier‐type reactions. In this communication, we have described a photoredox Barbier allylation of aldehydes mediated by bismuth, in absence of other metals as co‐reductants. Mild reaction conditions, tolerance of oxygen, and use of aqueous solvent make this photoredox methodology attractive for green and sustainable synthesis of homoallylic alcohols.
Thermocatalytic hydrogenation of CO2 into aromatics by tailor‐made catalysts: Recent advancements and perspectives
Authors: Wang Yang , Gao Xinhua , Wu Mingbo , Tsubaki Noritatsu
Published: January 2021

Considering the severe environmental issues brought by excessive carbon emissions, the utilization of CO2 as a feedstock for chemicals synthesis is gaining a lot of interest. CO2 hydrogenation into valuable chemicals using renewable energy is a promising strategy to alleviate the environmental pressures and reduce our strong dependence on fossil fuels simultaneously. Aromatics, as important chemicals in our daily life, can be synthesized by a tandem strategy that first converts CO2 into CO or methanol on Fe‐based active sites or reducible metal oxides, respectively, and then sequentially conducts CC coupling, dehydrogenation, and cyclization processes on acidic zeolites with unique topology structure for aromatics synthesis. This critical review focuses on the recent advancements in CO2 hydrogenation into high value‐added aromatics (CTA), in particular the key factors, such as the catalytic component, the acidity distribution of the zeolite, and the proximity effect between different active sites that regulate the aromatics selectivity. The reaction network and mechanism during the tandem process will be discussed to guide the rational design of highly efficient bifunctional/multifunctional catalysts for direct synthesis of aromatics by CO2 hydrogenation. Furthermore, the development directions and obstacles of CO2 utilization by hydrogenation technology will be predicted to pave the way for the practical application of greenhouse gas CO2 for valuable aromatics synthesis.

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Assessment of magnetite as a magnetic tracer for sediments in the study of ephemeral gully erosion: Conditioning factors of magnetic susceptibility
Authors: Zubieta Elena , Larrasoaña Juan C. , Aldaz Alaitz , Casalí Javier , Giménez Rafael
Published: January 2021

In gully erosion, the detached soil can be transported over long distances along the landscape. The eroded material can be redistributed and/or deposited on the soil surface along the landscape and then eventually be buried by newly eroded and deposited sediment. There can be significant variability of the soil conditions (e.g., texture and moisture content) over which the eroded material travels. The eroded material can be detected through the use of magnetic tracers attached to or mixed with the eroded soil. In this study we evaluated the degree to which the magnetic signal of the magnetite is conditioned by (i) burial depth of tracer, (ii) condition of soil covering the tracer and (iii) tracer concentration. In the laboratory containers were filled with a specific soil. In the filling process, a 0.5‐cm layer of a soil–magnetite mixture was interspersed in the soil profile at a certain depth. Experiments encompassed three different soil–tracer concentrations (1000:1, 200:1, 100:1), four burial depths of tracer (0 cm, 3 cm, 5 cm and 10 cm from soil surface), and two different soils. In each case, the magnetic susceptibility was measured with a susceptometer. Experiments were repeated with different soil moisture contents. If the tracer is located under the soil surface, a minimum soil–tracer concentration of 200:1 is required for its correct detection. The intensity of the magnetic signal decreases dramatically with the vertical distance of the tracer from the soil surface. The maximum detection depth for the tracer's magnetic signal is strongly dependent on the natural magnetic susceptibility of the soil, which masks the tracer's signal. Variation in soil moisture content does not significantly affect the magnetic signal. For extensive field studies, the soil–tracer volume to be handled would be very high and therefore, it is necessary to explore new tracer application techniques.
How to prevent ROP in preterm infants in Indonesia?
Authors: Siswanto Johanes Edy , Dijk Peter H. , Bos Arend F. , Sitorus Rita S. , Adisasmita Asri C. , Ronoatmodjo Sudarto , Sauer Pieter J. J.
Published: January 2021

Background and Aims

Retinopathy of prematurity (ROP) is a severe disease in preterm infants. It is seen more frequently in Low‐Middle Income Countries (LMIC) like Indonesia compared to High‐Income Countries (HIC). Risk factors for ROP development are ‐extreme‐ preterm birth, use of oxygen, neonatal infections, respiratory problems, inadequate nutrition, and blood and exchange transfusions. In this paper, we give an overview of steps that can be taken in LMIC to prevent ROP and provide guidelines for screening and treating ROP.

Methods

Based on the literature search and data obtained by us in Indonesia's studies, we propose guidelines for the prevention, screening, and treatment of ROP in preterm infants in LMIC.

Results

Prevention of ROP starts before birth with preventing preterm labor, transferring a mother who might deliver <32 weeks to a perinatal center and giving corticosteroids to mothers that might deliver <34 weeks. Newborn resuscitation must be done using room air or, in the case of very preterm infants (<29‐32 weeks) by using 30% oxygen. Respiratory problems must be prevented by starting continuous positive airway pressure (CPAP) in all preterm infants <32 weeks and in case of respiratory problems in more mature infants. If needed, the surfactant should be given in a minimally invasive manner, as ROP's lower incidence was found using this technique. The use of oxygen must be strictly regulated with a saturation monitor of 91‐95%. Infections must be prevented as much as possible. Both oral and parenteral nutrition should be started in all preterm infants on day one of life with preferably mothers' milk. Blood transfusions can be prevented by reducing the amount of blood needed for laboratory analysis.

Discussion

Preterm babies should be born in facilities able to care for them optimally. The use of oxygen must be strictly regulated. ROP screening is mandatory in infants born <34 weeks, and infants who received supplemental oxygen for a prolonged period. In case of progression of ROP, immediate mandatory treatment is required.

Conclusion

Concerted action is needed to reduce the incidence of ROP in LMIC. "STOP ‐ R1O2P3" is an acronym that can help implement standard practices in all neonatal intensive care units in LMIC to prevent development and progression.
Cross contamination meets misclassification: Awakening of CHP‐100 from sleeping beauty sleep—A reviewed model for Ewing's sarcoma
Authors: Dirks Wilhelm Gerhard , Capes‐Davis Amanda , Eberth Sonja , Fähnrich Silke , Wilting Jörg , Nagel Stefan , Steenpass Laura , Becker Jürgen
Published: January 2021

A human cell line of neuroblastic tissue, which was believed to have been lost to science due to its unavailability in public repositories, is revived and reclassified. In the 1970s, a triple set of neuroblastoma (NB) cell lines became available for research as MYCN‐amplified vs nonamplified models (CHP‐126/‐134 and CHP‐100, respectively). Confusingly, CHP‐100 was used in subsequent years as a model for NB and, since the 1990s, as a model for neuroepithelioma and later as a model for Ewing's sarcoma (ES), which inevitably led to non‐reproducible results. A deposit at a bioresource center revealed that globally available stocks of CHP‐100 were identical to the prominent NB cell line IMR‐32 and CHP‐100 was included into the list of misidentified cell lines. Now we report on the rediscovery of an authentic CHP‐100 cell line and provide evidence of incorrect classification during establishment. We show that CHP‐100 cells carry a t(11;22)(q24;q12) type II EWSR1‐FLI1 fusion and identify it as a classic ES. Although the question of whether CHP‐100 was a virtual and never existing cell line from the beginning is now clarified, the results of all relevant publications should be considered questionable. Neither the time of the cross‐contamination event with IMR‐32 is known nor was the final classification as a model for Ewing family of tumors available with an associated short tandem repeat profile. After a long road of errors and confusion, authentic CHP‐100 is now characterized as a type II EWSR1‐FLI1 fusion model 44 years after its establishment.
Another look at contagion across United States and European financial markets: Evidence from the credit default swaps markets
Authors: Tsionas Mike G. , Apergis Nicholas
Published: January 2021

The paper looks at the results of Apergis, Christou and Kynigakis (2019) and proposes a novel model that allows time variation in volatility, skewness and kurtosis, based on multivariate stable distributions. The analysis also looks at bank sector CDS, insurance sector CDS, sovereign bonds, equity and volatility indices. The findings corroborate their results and indicate significant evidence of contagion, especially through the channels of co‐skewness and co‐kurtosis. In addition, it establishes a higher order channel of causality between co‐skewness and co‐kurtosis.
RETRACTED: Isosorbide mononitrate for cervical ripening in induction of labor for pregnant women with PROM at or post term
Authors: Afifi Ahmed N. , Taymour Mohammad A. , El‐Khayat Waleed M.
Published: January 2021

Objective

To evaluate the efficacy of isosorbide mononitrate (IMN) for stimulating cervical ripening among pregnant women with premature rupture of membranes (PROM) at or post term.

Methods

A prospective randomized double‐blind, placebo‐controlled trial at Kasr El‐Ainy Hospital, Cairo, Egypt, from October 2018 to May 2019. Pregnant women at or post term with PROM and unfavorable cervix (Bishop score ≤6) were randomly assigned to receive intra‐vaginal IMN (n = 70) or placebo (n = 70) before admission for induction of labor. The main outcome was induction to the delivery interval. Data were compared between groups by t test.

Results

The mean ± SD duration from the initial dose of IMN/placebo to the beginning of the active phase of labor was significantly shorter in the IMN group than in the control group (9.7 ± 5.6 h vs. 12.9 ± 5.3 h). The IMN group also had a shorter time interval from induction to delivery (P < 0.01). There was no difference in adverse effects between the groups.

Conclusion

Intra‐vaginal IMN for cervical ripening in the induction of labor among pregnant with PROM at or post term was found to be effective and safe with minimal adverse effects, and good neonatal and maternal outcomes.

ClinicalTrials.gov: NCT03665779.
Long non‐coding RNA UCA1 correlates with elevated disease severity, Th17 cell proportion, inflammatory cytokines, and worse prognosis in acute ischemic stroke patients
Authors: Ren Bin , Song Zhiyuan , Chen Laizhao , Niu Xiaomin , Feng Qiang
Published: January 2021

Background

This study aimed to explore the association of long non‐coding RNA urothelial carcinoma‐associated 1 (lncRNA UCA1) expression with disease severity, inflammation, and prognosis in acute ischemic stroke (AIS) patients.

Methods

The lncRNA UCA1 expression of blood CD4+ T cells from 160 first‐episode AIS patients and 160 non‐AIS patients with high‐stroke‐risk factors (as controls) was detected by reverse transcription quantitative polymerase chain reaction. For AIS patients, interleukin (IL)‐6, IL‐17, and intracellular adhesion molecule‐1 (ICAM1) were determined by enzyme‐linked immunosorbent assay; Th17 cell ratio in CD4+ T cells was detected by flow cytometry. Their follow‐up data were recorded up to 36 months, recurrence of stroke or death. The recurrence‐free survival (RFS) analysis was assessed according to the follow‐up data.

Results

LncRNA UCA1 expression was higher in AIS patients compared to controls (p < 0.001), and it was positively correlated to national institute of health stroke scale score (r = 0.436, p < 0.001), Th17 cell ratio (r = 0.398, p < 0.001), IL‐6 (r = 0.204, p = 0.010), IL‐17 (r = 0.326, p < 0.001), and ICAM1 (r = 0.276, p < 0.001) in AIS patients. Regarding prognosis, lncRNA UCA1 expression was elevated in 2‐year recurrence/death AIS patients compared to those patients without recurrence or death within 2 years (p = 0.033), also increased in 3‐year recurrence/death AIS patients compared to those patients without recurrence or death within 3 years (p = 0.008). Furthermore, high lncRNA UCA1 expression was associated with worse accumulating RFS (p = 0.017) in AIS patients.

Conclusion

LncRNA UCA1 might sever as a candidate prognostic biomarker in AIS patients, suggesting its potency for AIS management.
Further Evaluation of Coproporphyrins as Clinical Endogenous Markers for OATP1B
Authors: Feng Sheng , Bo Qingyan , Coleman Hugh A. , Charoin Jean Eric , Zhu Mingfen , Xiao Jim , Jin Yuyan
Published: January 2021

Coproporphyrins (CP‐I and CP‐III) in plasma are considered potential markers for assessing liver organic anion‐transporting polypeptide transporter OATP1B activity and monitoring OATP1B‐mediated drug‐drug interactions (DDIs) in clinical settings. However, the effect of altered renal clearance (CLrenal) on CP‐I and CP‐III plasma exposure has rarely been examined. Therefore, the purpose of this study is to further evaluate CP‐I and CP‐III as clinical endogenous markers for OATP1B activity and to investigate the impact of CLrenal on DDI assessments for the first time. In this study, 18 healthy participants were recruited to receive RO7049389 (a potential inhibitor of OATP1B) 800 mg twice daily for 6 days and a single dose of pitavastatin (a probe drug of OATP1B) before and after RO7049389 treatment. Plasma concentrations of pitavastatin, CP I, CP III, and the amounts of CP‐I and CP‐III excreted in urine were measured. Seventeen healthy participants completed the study. After multiple doses of RO7049389, the area under the plasma concentration–time curve from time 0 to 12 hours of pitavastatin increased 1.95‐fold (90% confidence interval [CI], 1.58‐2.41), while for CP‐I and CP‐III it increased 3.00‐fold (90%CI, 2.35‐3.82) and 2.84‐fold (90%CI, 2.22‐3.65), respectively. Concurrently, the CLrenal of CP‐I decreased by 31% (90%CI, 23%‐39%), and that of CP‐III decreased by 70% (90%CI, 61%‐77%). In conclusion, CP‐I and CP‐III in plasma display the potential to be applied as endogenous markers for the evaluation of OATP1B inhibition in clinical trials. While renal transporters contribute significantly to the CLrenal of CP‐III, it would be better to investigate the impact of the CLrenal on plasma exposure of CP‐III during clinical DDI assessments.
Exosomes derived from osteogenic tumor activate osteoclast differentiation and concurrently inhibit osteogenesis by transferring COL1A1‐targeting miRNA‐92a‐1‐5p
Authors: Yu Lijuan , Sui Bingdong , Fan Weixiao , Lei Lin , Zhou Lei , Yang Liu , Diao Yanjun , Zhang Yue , Li Zhuo , Liu Jiayun , Hao Xiaoke
Published: January 2021

In patients with prostate cancer (PCa), bone lesions appear osteoblastic in radiographs; however, pathological fractures frequently occur in PCa patients, and bone resorption is observed in all metastatic lesions under histopathologic assessment. The mechanisms that balance the activities of osteoblasts and osteoclasts in PCa patients remain unclear. We unexpectedly discovered that PCa exosomes are critical mediators in the regulation of bone homeostasis that results in osteoclastic lesions and thereby promotes tumor growth in bone. We evaluated how exosomes derived from osteoblastic, osteoclastic, and mixed PCa cell lines affect osteoblast and osteoclast differentiation, revealing that all three types of PCa exosomes promoted osteoclastogenesis in vitro and induced osteolysis in vivo. Mechanistically, microRNAs (miRNAs) delivered by PCa exosomes were found to play several key roles in bone homeostasis. Among the delivered miRNAs, miR‐92a‐1‐5p, the most abundant miRNA, downregulated type I collagen expression by directly targeting COL1A1, and thus promoting osteoclast differentiation and inhibiting osteoblastogenesis. Furthermore, PCa exosomes also markedly reduced type I collagen expression in vivo. Our findings not only offer a novel perspective on tumor bone metastasis, where—contrary to our initial hypothesis—exosomes derived from an osteoblastic tumor induce osteoclast differentiation, but also suggest potential therapeutic targets for PCa bone metastasis.
Gait biomechanics: A clinically relevant outcome measure for preclinical research of musculoskeletal trauma
Authors: Motherwell Jessica M. , Hendershot Brad D. , Goldman Stephen M. , Dearth Christopher L.
Published: January 2021

Traumatic injuries to the musculoskeletal system are the most prevalent of those suffered by United States Military Service members and accounts for two‐thirds of initial hospital costs to the Department of Defense. These combat‐related wounds often leave survivors with life‐long disability and represent a significant impediment to the readiness of the fighting force. There are immense opportunities for the field of tissue engineering and regenerative medicine (TE/RM) to address these musculoskeletal injuries through regeneration of damaged tissues as a means to restore limb functionality and improve quality of life for affected individuals. Indeed, investigators have made promising advancements in the treatment for these injuries by utilizing small and large preclinical animal models to validate therapeutic efficacy of next‐generation TE/RM‐based technologies. Importantly, utilization of a comprehensive suite of functional outcome measures, particularly those designed to mimic data collected within the clinical setting, is critical for successful translation and implementation of these therapeutics. To that end, the objective of this review is to emphasize the clinical relevance and application of gait biomechanics as a functional outcome measure for preclinical research studies evaluating the efficacy of TE/RM therapies to treat traumatic musculoskeletal injuries. Specifically, common musculoskeletal injuries sustained by service members—including volumetric muscle loss, post‐traumatic osteoarthritis, and composite tissue injuries—are examined as case examples to highlight the use of gait biomechanics as an outcome measure using small and large preclinical animal models.
Effect of black chokeberry pomace extract incorporation on the physical and oxidative stability of water‐in‐oil‐in‐water emulsion
Authors: Eisinaitė Viktorija , Kazernavičiūtė Rita , Kaniauskienė Ingrida , Venskutonis Petras Rimantas , Leskauskaitė Daiva
Published: January 2021

BACKGROUND

Despite the obvious benefits of double emulsions in reducing fat content by replacing it with the water phase, their physical and oxidative stability remains a major concern. The objective of this study was to determine the ability of black chokeberry extract to inhibit lipid oxidation during storage at 4 °C for 60 days when different amounts of the extract were added to the inner water phase of the double emulsion. In the first step, the physical stability of the emulsions was evaluated.

RESULTS

Higher amount of the extract caused the formation of double emulsions with smaller droplets and higher viscosity. Throughout the whole storage period, the double emulsions showed good physical stability and high encapsulation efficiency (EE) of the extract (>95%) in the inner water phase. The positive effect of the extract on the oxidative stability of the double emulsions was shown by measuring changes in peroxide values and conjugated dienes and through the Oxipres and Rancimat tests during the convenient and accelerated storage of emulsions for 60 days.

CONCLUSION

The higher amount of extract suppressed lipid oxidation to a higher extent given the significant amount of polyphenolics in the extract. © 2021 Society of Chemical Industry
Kinetic studies of excited singlet oxygen atom O(1D) reactions with ethanol
Authors: Zhong Hongtao , Yan Chao , Teng Chu C. , Chen Timothy Y. , Wysocki Gerard , Ju Yiguang
Published: January 2021

The multichannel reaction of excited singlet oxygen atom with ethanol, O(1D) + C2H5OH (1), was studied in a photolysis flow reactor coupled with mid‐infrared Faraday rotation spectroscopy (FRS) and UV‐IR direct absorption spectroscopy (DAS) at 297 K with reactor pressures of 60, 120, and 150 Torr (bath He). The excited singlet oxygen atom was generated through the photolysis of O3 at 266 nm. The photon flux and O(1D) concentrations were determined by in situ actinometry based on O3 depletion. Temporal profiles of OH and H2O were monitored via DAS signals at ca. 3568.62 and 3568.29 cm−1, while temporal profiles of HO2 were measured via FRS signals at ca. 1396.90 cm−1. The branching ratios of the target reaction (1) were determined by fitting temporal profiles to simulations from an in‐house reaction mechanism. Two major reaction channels were identified as CH3CHOH + OH and CH3O + CH2OH, and their branching ratios were determined as 0.46 ± 0.12 and 0.42 ± 0.11, respectively. A specific HO2 + RO2 reaction between HO2 and O2CH2CH2OH (β‐RO2) at the low‐temperature range is estimated in this work as HO2 + O2CH2CH2OH products with a rate constant of 7 × 10−12 cm3 molecule−1 s−1.
University presses and the impact of COVID‐19
Authors: Watkinson Charles
Published: January 2021

University presses occupy a distinctive field of publishing, heavily tied to the fortunes of the universities and colleges in which they are usually situated. COVID‐19 has catalysed their adoption of digital technologies; focused their commitments to social justice; and given new impetus to business models and formats that fully leverage the Internet, especially open access. Economic pressures on higher education that seem set only to increase are also driving university presses to more interdependent approaches and an emphasis on the contributions of the university press network to knowledge infrastructure for the humanities and social sciences. This article explores how university presses have reacted to the COVID‐19 pandemic, with particular reference to the experiences of the University of Michigan Press. It concludes that the diversity of types of university presses is one of the greatest strengths of this field of publishing and makes it resilient in a time of unprecedented change.
Brainstem Reflexes in Idiopathic Cervical Dystonia: Does Medullary Dysfunction Play a Role?
Authors: Manzo Nicoletta , Tocco Pierluigi , Ginatempo Francesca , Bertolasi Laura , Rocchi Lorenzo
Published: January 2021

Background

Neurophysiological markers in dystonia have so far not been sistematically applied in clinical practice due to limited reproducibility of results and low correlations with clinical findings. Exceptions might be represented by the blink reflex (BR), including its recovery cycle (BRRC) and the trigemino‐cervical reflex (TCR) which, compared to other neurophysiological methods, have shown more consistent alterations in cervical dystonia (CD). However, a comparison between the two techniques, and their possible correlation with disease symptoms, have not been thoroughly investigated.

Objectives

To assess the role of BR, BRCC and TCR in the pathophysiology of idiopathic cervical dystonia.

Methods

Fourteen patients and 14 age‐matched healthy controls (HC) were recruited. Neurophysiological outcome measures included latency of R1 and R2 components of the BR, R2 amplitude, BRRC, latency and amplitude of P19/N31 complex of TCR. Clinical and demographic features of patients were also collected, including age at disease onset, disease duration, presence of tremor, sensory trick and pain. The Toronto Western Spasmodic Torticollis Rating Scale was used to characterize dystonia.

Results

Compared to HC, CD patients showed increased latency of the BR R2 and decreased suppression of the BRRC. They also showed increased latency of the P19 and decreased amplitude of P19/N31 complex of TCR. The latency of P19 component of TCR was positively correlated with disease duration.

Conclusions

We propose that the increased latency of R2 and P19 observed here might be reflective of brainstem dysfunction, mediated either by local interneuronal excitability changes or by subtle structural damage.
NLRP3 inflammasome in cardiovascular diseases: Pathophysiological and pharmacological implications
Authors: Pellegrini Carolina , Martelli Alma , Antonioli Luca , Fornai Matteo , Blandizzi Corrado , Calderone Vincenzo
Published: January 2021

Growing evidence points out the importance of nucleotide‐binding oligomerization domain leucine‐rich repeat and pyrin domain‐containing protein 3 (NLRP3) inflammasome in the pathogenesis of cardiovascular diseases (CVDs), including hypertension, myocardial infarct (MI), ischemia, cardiomyopathies (CMs), heart failure (HF), and atherosclerosis. In this regard, intensive research efforts both in humans and in animal models of CVDs are being focused on the characterization of the pathophysiological role of NLRP3 inflammasome signaling in CVDs. In addition, clinical and preclinical evidence is coming to light that the pharmacological blockade of NLRP3 pathways with drugs, including novel chemical entities as well as drugs currently employed in the clinical practice, biologics and phytochemicals, could represent a suitable therapeutic approach for prevention and management of CVDs. On these bases, the present review article provides a comprehensive overview of clinical and preclinical studies about the role of NLRP3 inflammasome in the pathophysiology of CVDs, including hypertension, MI, ischemic injury, CMs, HF and atherosclerosis. In addition, particular attention has been focused on current evidence on the effects of drugs, biologics, and phytochemicals, targeting different steps of inflammasome signaling, in CVDs.
Pharmacological Therapy Determines the Gut Microbiota Modulation by a Pomegranate Extract Nutraceutical in Metabolic Syndrome: A Randomized Clinical Trial
Authors: Cortés‐Martín Adrián , Iglesias‐Aguirre Carlos Eduardo , Meoro Amparo , Selma María Victoria , Espín Juan Carlos
Published: January 2021

Scope

Poly‐pharmacological therapy shapes the gut microbiota (GM) in metabolic syndrome (MetS) patients. The effects of polyphenols in poly‐medicated MetS patients are unknown.

Methods and results

A randomized, placebo‐controlled, double‐blinded, and crossover trial in poly‐medicated MetS patients (n=50) explored whether the effects of a pomegranate extract nutraceutical (PE, 320 mg phenolics/day for 1 month) are affected by the drug therapy. Considering the lipid‐lowering (LL‐), anti‐hypertensive (HP‐) and(or) anti‐diabetic (AD‐) treatments: GM (16S rRNA sequencing), short‐chain fatty acids, 40 inflammatory‐metabolic and endotoxemia‐related biomarkers, associations between biomarkers and GM with 53 cardiometabolic dysfunctions‐related single‐nucleotide polymorphisms (SNPs), and urolithin metabotypes (UMs) influence are evaluated. Representative SNPs‐GM associations after PE include Lactococcus and ClostridiumXIVa with rs5443‐GNB3 (G‐protein‐β‐polypeptide‐3) and ClostridiumXIVa with rs7903146‐TCF7L2 (transcription‐factor‐7‐like‐2) and rs1137101‐LEPR (leptin‐receptor). PE decreases sICAM‐1 in LL‐patients and the lipopolysaccharide‐binding protein in all the patients. PE does not affect the other patients’ markers as a group or stratifying by UMs. After PE, Lactococcus increases in AD‐, LL‐, and HP‐patients, Bifidobacterium increases in LL‐ and AD‐, while Clostridium XIVa decreases in non‐LL‐ and non‐HP‐patients.

Conclusion

The prebiotic effect of PE depends on the medication, mainly on HP‐treatments. Targeting GM can complement MetS therapy, but the patients’ drug therapy should be considered individually.
Female reproductive function after treatment of childhood acute lymphoblastic leukemia
Authors: Roshandel Roxanne , van Dijk Marloes , Overbeek Annelies , Kaspers Gertjan , Lambalk Cornelis , Beerendonk Catharina , Bresters Dorine , van der Heiden‐van der Loo Margriet , van den Heuvel‐Eibrink Marry , Kremer Leontien , Loonen Jacqueline , van der Pal Helena , Ronckers Cecile , Tissing Wim , Versluys Birgitta , van Leeuwen Flora , van den Berg Marleen , van Dulmen‐den Broeder Eline ,   LATER‐VEVO Study Group
Published: January 2021

Background

The aim was to evaluate self‐reported reproductive characteristics and markers of ovarian function in a nationwide cohort of female survivors of childhood acute lymphoblastic leukemia (ALL), because prior investigations have produced conflicting data.

Procedure

Self‐reported reproductive characteristics were assessed by questionnaire among 357 adult 5‐year survivors, treated between 1964 and 2002, and 836 controls. Ovarian function was assessed by serum levels of anti‐Müllerian hormone (AMH), follicle‐stimulating hormone (FSH), and inhibin B and by antral follicle count (AFC). Differences between controls and (subgroups of) survivors (total group, chemotherapy [CT]‐only group, CT and radiotherapy [RT] group) were analyzed.

Results

Survivors treated with CT only do not differ from controls regarding timing of menarche, virginity status, desire for children, or pregnancy rates. Compared to controls, the CT+RT group was at significantly increased risk of a younger age at menarche (P < .01), virginity, an absent desire for children, and lower pregnancy rates (odds ratio [OR] [95% CI]: 0.3 [CI 0.1‐0.6], 0.5 [0.3‐0.9], and 0.4 [0.2‐0.9], respectively). Survivors in the CT‐only group were significantly younger at the birth of their first child. Pregnancy outcomes were not significantly different between any (sub)groups. Survivors treated with total body irradiation (TBI) or hematopoietic stem cell transplantation (HSCT) are at increased risk of abnormal markers of ovarian function.

Conclusion

Reproductive function of ALL survivors treated with CT only does not differ from controls. However, survivors additionally treated with RT seem to be at an increased risk of certain adverse reproductive outcomes. Providing personalized counseling about (future) reproductive health risks in this group is imperative.
Metastatic progression in infants diagnosed with stage 4S neuroblastoma. A study of the Italian Neuroblastoma Registry
Authors: Parodi Stefano , Sorrentino Stefania , Cataldo Andrea Di , Tondo Annalisa , Fagnani Anna Maria , Perri Patrizia , Gigliotti Anna Rita , Erminio Giovanni , Corrias Maria Valeria , De Bernardi Bruno
Published: January 2021

Purpose

Stage 4S neuroblastoma, a tumor affecting infants, is characterized by the capacity to regress spontaneously and high cure rate. About a third of these infants undergo tumor progression requiring antitumor treatment and 10‐15% eventually die. In case of metastatic progression, it may occur either at 4S sites (mainly liver) or sites characterizing stage 4 (mainly bone). Aim of this study was to estimate incidence, presenting features and outcome of infants who progressed to stage 4S or stage 4 sites.

Patients

Of 280 Italian infants diagnosed with stage 4S neuroblastoma between 1979 and 2013 and registered in the Italian Neuroblastoma Registry, 268 were evaluable for this study, of whom 57 developed metastatic progression.

Results

Progression to stage 4S sites occurred in 29/268 infants (10.8%) (Group A) and to stage 4 in 28/268 (10.4%) (Group B). No significant difference was observed between the two groups at the time of diagnosis. At the time of progression, Group A infants were younger (7.3 vs 14.4 months, P = .001) and had a shorter interval from diagnosis to progression (3.8 vs 9.6 months, P = .001). Survival after progression was worse for Group B infants (45% vs 69%, P = .058) and was associated with age at diagnosis lower than 2 months (P = .005) and adrenal primary tumor site (P = .008). Survival rates increased for both groups along the study period.

Conclusions

Infants who progressed to stage 4 did worse, possibly in relation to older age at progression and longer interval between diagnosis and progression. Large prospective studies of these patients may lead to more effective treatments.