bluuebunny/crossref_metadata_2025 huggingface dataset:
meso‐ and β‐Pyrrole‐Linked Chlorin‐Bacteriochlorin Dyads for Promoting Far‐Red FRET and Singlet Oxygen Production
Authors: Dukh Mykhaylo , Tabaczynski Walter A. , Seetharaman Sairaman , Ou Zhongping , Kadish Karl M. , D'Souza Francis , Pandey Ravindra K.
Published: July 2020

A series of chlorin‐bacteriochlorin dyads (derived from naturally occurring chlorophyll‐a and bacteriochlorophyll‐a), covalently connected either through the meso‐aryl or β‐pyrrole position (position‐3) via an ester linkage have been synthesized and characterized as a new class of far‐red emitting fluorescence resonance energy transfer (FRET) imaging, and heavy atom‐lacking singlet oxygen‐producing agents. From systematic absorption, fluorescence, electrochemical, and computational studies, the role of chlorin as an energy donor and bacteriochlorin as an energy acceptor in these wide‐band‐capturing dyads was established. Efficiency of FRET evaluated from spectral overlap was found to be 95 and 98 % for the meso‐linked and β‐pyrrole‐linked dyads, respectively. Furthermore, evidence for the occurrence of FRET from singlet‐excited chlorin to bacteriochlorin was secured from studies involving femtosecond transient absorption studies in toluene. The measured FRET rate constants, kFRET, were in the order of 1011 s−1, suggesting the occurrence of ultrafast energy transfer in these dyads. Nanosecond transient absorption studies confirmed relaxation of the energy transfer product, 1BChl*, to its triplet state, 3Bchl*. The 3Bchl* thus generated was capable of producing singlet oxygen with quantum yields comparable to their monomeric entities. The occurrence of efficient FRET emitting in the far‐red region and the ability to produce singlet oxygen make the present series of dyads useful for photonic, imaging and therapy applications.
Exploiting colorimetric relationships in characterizing the spectral response functions of the human visual system directly from colour matching functions
Authors: Tooms Michael S.
Published: July 2020

The linear relationship between the spectral response functions (SRFs) of a three‐colour response system and the set of the corresponding colour matching functions (CMFs) for a particular set of primaries, in the form of three simultaneous equations, is the principal fundamental approach adopted in this article in determining the characteristics of the former. After reviewing, evaluating, and where necessary processing the three sets of 2° field CMFs derived by the historic researchers, Guild, Wright, and Stiles & Burch, they were used with three sets of CMFs to SRFs transforms with adjustable matrix coefficients, respectively, to provide three closely matched sets of SRFs. These close matches then formed the basis for the three sets of potential human visual system (HVS) SRFs, which with three further transforms, whose coefficients are based upon the response of the SRFs at the primary wavelengths, then generate, respectively, a close match to each of the historic sets of CMFs. The precept adopted is that given the relative trichromatic sensitivity of the HVS SRFs and a set of three spectral primaries of defined wavelength and known luminosities, a mathematical relationship may be derived between them that produces a corresponding set of CMFs related to the wavelengths of the primaries selected. In an ideal situation then the three sets of SRFs obtained which each produce a match of the derived CMFs to the original CMFs, should also produce a match with each other and represent the SRFs of the HVS. The same procedure was also applied to the Stiles & Burch 10° SMFs to obtain a 10° version of the HVS SRFs. This article outlines the structure of the mathematical tool evolved and the design of the spreadsheet used to derive and build the various relationships, together with the reasoning for each of the steps in the process. The resulting tool is then used with processed forms of the CMFs of the historic researchers, to show that, within the limits of the experimental errors of the original works, the resulting derived CMFs compare favorably with those originally established by experiment, and furthermore, the three associated individual sets of SRFs match, providing strong evidence that they do indeed represent the SRFs of the human vision system.
Flow Chemistry for Cycloaddition Reactions
Authors: García‐Lacuna Jorge , Domínguez Gema , Pérez‐Castells Javier
Published: July 2020

Abstract: Continuous flow reactors form part of a rapidly growing research area that has changed the way synthetic chemistry is performed not only in academia but also at the industrial level. This Review highlights the most recent advances in cycloaddition reactions performed in flow systems. Cycloadditions are atom‐efficient transformations for the synthesis of carbo‐ and heterocycles, involved in the construction of challenging skeletons of complex molecules. The main advantages of translating these processes into flow include using intensified conditions, safer handling of hazardous reagents and gases, easy tuning of reaction conditions, and straightforward scaling up. These benefits are especially important in cycloadditions such as the copper(I)‐catalyzed azide alkyne cycloaddition (CuAAC), Diels‐Alder reaction, ozonolysis and [2+2] photocycloadditions. Some of these transformations are key reactions in the industrial synthesis of pharmaceuticals.
Exploiting non‐orthogonal multiple access in downlink coordinated multipoint transmission with the presence of imperfect channel state information
Authors: Murti Fahri Wisnu , Siregar Rahmat Faddli , Royyan Muhammad , Shin Soo Young
Published: July 2020

In this paper, the impact of imperfect channel state information (CSI) on a downlink coordinated multipoint (CoMP) transmission system with non‐orthogonal multiple access (NOMA) is investigated since perfect knowledge of a channel cannot be guaranteed in practice. Furthermore, the channel estimation error is applied to estimate the channel information wherein its a priori of variance is assumed to be known. The impact of the number of coordinated base stations (BSs) on downlink CoMP NOMA is investigated. Users are classified into one of two groups according to their position within the cell, namely, cell‐center user (CCU) and cell‐edge user (CEU). In this paper, ergodic capacity and sum capacity for both CCU and CEU are derived as closed forms. In addition, various experiments are conducted with different parameters such as SNR, error variance, and power allocation to show their impact on the CoMP method. The results show that CoMP NOMA outperforms the CoMP orthogonal multiple access (OMA) wherein the condition of the channel impacts the performance of CoMP NOMA less. It is worth noting that a higher number of coordinated BSs enhances the total capacity of CoMP NOMA. Finally, the performance analysis is validated due to the close accordance between the analytical and simulation results.
Early predictors of treatment outcome in a partial hospital program for adolescent anorexia nervosa
Authors: Brown Tiffany A. , Murray Stuart B. , Anderson Leslie K. , Kaye Walter H.
Published: July 2020

Objective

Previous research supports the relevance of early symptom change in eating disorder (ED) treatment; however, few studies have distinguished early weight change from early change in ED psychopathology, particularly in higher levels of care. Thus, the present study examined whether early change in weight and ED psychopathology predicted outcome for adolescents with anorexia nervosa (AN) in a partial hospitalization program.

Method

Adolescents with AN (n = 99) completed assessments at admission, 1‐month after treatment admission, discharge, and 6‐month follow‐up.

Results

Higher admission percent expected body weight (%EBW), greater early change in %EBW, longer duration of treatment, shorter length of illness, and earlier age of onset predicted greater change in %EBW at discharge, but not follow‐up. Greater ED psychopathology at admission and greater early change in ED psychopathology predicted later change in ED symptoms at discharge, but not follow‐up. Neither early change in %EBW nor ED psychopathology predicted likelihood of remission at discharge and follow‐up.

Discussion

Results support the importance of early change in predicting later change in the same ED outcome variables and suggest that early change in both %EBW and ED psychopathology in adolescents may be an important area for future research.
Space use by giant anteaters (Myrmecophaga tridactyla) in a protected area within human‐modified landscape
Authors: Bertassoni Alessandra , Mourão Guilherme , Bianchi Rita de Cassia
Published: July 2020

Spatial ecology data are essential for conservation purposes, especially when extinction risk is influenced by anthropogenic actions. Space use can reveal how individuals use the habitat, how they organize in space, and which components are key resources for the species.

We evaluated the space use and multiscale habitat selection of giant anteaters (Myrmecophaga tridactyla), a vulnerable Neotropical mammal, in a Cerrado site within a human‐modified landscape in southeastern Brazil.

We used GPS transmitters to track eight anteaters in the wild. With the resulting dataset, we estimated home range and core‐area sizes and then used two overlap indexes. We assessed habitat selection by compositional analysis and analyzed events of spatio‐temporal proximity.

The average Brownian bridge kernel estimate of home range size was 3.41 km2 (0.92–7.9). Regarding home range establishment, five individuals showed resident behavior. Males (n = 4) had larger home ranges and were more active than females (n = 4). Despite the spatial overlap of home range (above 40% in four dyads), maximum temporal space sharing was 18%. Giant anteaters were found in proximity. Habitat selection favored savanna, and exotic timber plantation was always avoided. Roads and built‐up areas were selected secondarily at the landscape level.

The selection of anthropogenic sites denotes behavioral plasticity regarding modified habitats. However, the high selectivity for savanna, at all levels, demonstrates a high dependence on natural habitats, which provide the necessary resources for the species. The recurrent proximity of male–to‐female anteaters may indicate reproductive behavior, which is essential for maintaining this isolated population.
Modulation of the acute defence reaction by eplerenone prevents cardiac disease progression in viral myocarditis
Authors: Tschöpe Carsten , Van Linthout Sophie , Jäger Sebastian , Arndt Robert , Trippel Tobias , Müller Irene , Elsanhoury Ahmed , Rutschow Susanne , Anker Stefan D. , Schultheiss Heinz‐Peter , Pauschinger Matthias , Spillmann Frank , Pappritz Kathleen
Published: July 2020

Aims

Left ventricular (LV) dysfunction in viral myocarditis is attributed to myocardial inflammation and fibrosis, inducing acute and long‐time cardiac damage. Interventions are not established. On the basis of the link between inflammation, fibrosis, aldosterone, and extracellular matrix regulation, we aimed to investigate the effect of an early intervention with the mineralocorticoid receptor antagonist (MRA) eplerenone on cardiac remodelling in a murine model of persistent coxsackievirus B3 (CVB3)‐induced myocarditis.

Methods and results

SWR/J mice were infected with 5 × 104 plaque‐forming units of CVB3 (Nancy strain) and daily treated either with eplerenone (200 mg/kg body weight) or with placebo starting from Day 1. At Day 8 or 28 post infection, mice were haemodynamically characterized and subsequently sacrificed for immunohistological and molecular biology analyses. Eplerenone did not influence CVB3 load. Already at Day 8, 1.8‐fold (P < 0.05), 1.4‐fold (P < 0.05), 3.2‐fold (P < 0.01), and 2.1‐fold (P < 0.001) reduction in LV intercellular adhesion molecule 1 expression, presence of monocytes/macrophages, oxidative stress, and apoptosis, respectively, was observed in eplerenone‐treated vs. untreated CVB3‐infected mice. In vitro, eplerenone led to 1.4‐fold (P < 0.01) and 1.2‐fold (P < 0.01) less CVB3‐induced cardiomyocyte oxidative stress and apoptosis. Furthermore, collagen production was 1.1‐fold (P < 0.05) decreased in cardiac fibroblasts cultured with medium of eplerenone‐treated vs. untreated CVB3‐infected HL‐1 cardiomyocytes. These ameliorations were in vivo translated into prevention of cardiac fibrosis, as shown by 1.4‐fold (P < 0.01) and 2.1‐fold (P < 0.001) lower collagen content in the LV of eplerenone‐treated vs. untreated CVB3‐infected mice at Days 8 and 28, respectively. This resulted in an early and long‐lasting improvement of LV dimension and function, as indicated by reduced LV end‐systolic volume and end‐diastolic volume, and an increase in LV contractility (dP/dtmax) and LV relaxation (dP/dtmin), respectively (P < 0.05).

Conclusions

Early intervention with the MRA eplerenone modulates the acute host and defence reaction and prevents cardiac disease progression in experimental CVB3‐induced myocarditis without aggravation of viral load. The findings advocate for an initiation of therapy of viral myocarditis as early as possible, even before the onset of inflammation‐induced myocardial dysfunction. This may also have implications for coronavirus disease‐19 therapy.
Significant Improvement of the Electrochemical Performance of CoO Nanoparticles Through Activating Synergistic Effects by Doping with Nickel
Authors: Zhou Ruoyu , Bi Xiaofeng , Yuan Xizhi , Zhang Ling , Huang Qingsong
Published: July 2020

In order to find a more optimized electrode material for supercapacitors, hydrothermally manufactured CoO nanoparticles doped with Ni were prepared in this research, and capacitor electrochemical performances were compared with those of non‐doped CoO nanoparticles. The promoting electrochemical performances of doped CoO nanoparticles were demonstrated by specific capacitance rising significantly from 151.9 F/g of non‐doped one to 279.5 F/g in current density of 1 A/g by galvanostatic charge‐discharge measurements and from 151.9 F/g to 270.6 F/g in cyclic voltammetry experiments with a scan rate of 2 mV/s. Performance of doped CoO particles is proved to be better because of the increased specific surface area, decreasing pore radius distribution, most probable aperture reducing, as well as the more suitable hole longitudinal section features. Moreover, the upgraded electrode material exhibits significant beneficial synergistic effects (both capacitance expansion and Faradaic output steadiness), as well as high capacity retention (106 % after 500 cycling tests). Our findings pave a new way to obtain supercapacitor electrode materials with better electrochemical performance.
Electromagnetic bandgap structure and split ring slot‐based monopole antenna for ultra‐wideband applications with dual band notch characteristics
Authors: Bhatia Sumeet Singh , Sivia Jagtar Singh , Sharma Narinder , Sharma Vipul
Published: July 2020

Reduced lightweight microstrip patch antennas have attracted considerable attention in ultra‐wideband (UWB) applications. In this article, a novel modified circular ultra‐wideband monopole antenna with dual‐band notch characteristics is proposed. A circular split‐ring slot and a mushroom‐electromagnetic bandgap‐type structure are employed to realize the dual‐band notch characteristics. The proposed antenna exhibits the bandwidth of 2.0‐12 GHz with a Voltage Standing Wave Ratio <2 except at the WiMAX band of 3.2‐3.7 GHz and wireless local area network band of 5.1‐5.8 GHz. The simulated and measured results of the proposed antenna, along with the design parameters, are reported and discussed in detail. The results show that the antenna is suitable for UWB applications.
On the small‐scale fractal geometrical structure of a living coral reef barrier
Authors: Sous Damien , Bouchette Frédéric , Doerflinger Erik , Meulé Samuel , Certain Raphael , Toulemonde Gwladys , Dubarbier Benjamin , Salvat Bernard
Published: July 2020

The topographical complexity of coral reefs is of primary importance for a number of hydrodynamical and ecological processes. The present study is based on a series of high‐resolution seabottom elevation measurements along the Maupiti Barrier Reef, French Polynesia. Several statistical metrics and spectral analysis are used to characterize the spatial evolution of the coral geometrical structure from the reef crest to the backreef. A consistent fractal‐like power law exists in the spectral density of bottom elevation for length scales between 0.1 and 7 m, while at larger scale, the reef structure shows a different pattern. Such a fine characterization of the reef geometrical structure provides key elements to reconstruct the reef history, to improve the representation of reef roughness in hydrodynamical models and to monitor the evolution of coral reef systems in the context of global change. © 2020 John Wiley & Sons, Ltd.
Dual and triple tasks performance in institutionalized prefrail and frail older adults
Authors: Lorenzo‐López Laura , Campos‐Magdaleno María , López‐López Rocío , Facal David , Pereiro Arturo X. , Maseda Ana , Blanco‐Fandiño Julia , Millán‐Calenti José Carlos
Published: July 2020

Objective

The aim of this pilot study was to investigate differences on dual‐ and triple‐task performance in institutionalized prefrail and frail older adults. Performance on these tasks is relevant since many activities of daily living involve simultaneous motor and cognitive tasks.

Methods

We used a phenotypic description of frailty based on the presence or absence of five criteria related to physical fitness and metabolism (unintentional weight loss, self‐reported exhaustion, muscle weakness, low gait speed, and low physical activity). Thirty‐three institutionalized older adults (≥ 65 years, 78.8% females) were divided according to their frailty status. Participants completed cognitive tasks (a phonemic verbal fluency task and a visuospatial tracking task) while cycling on a stationary cycle (upper‐ and lower‐extremity function was assessed). Cycling (number of arm and foot cycles) and cognitive (number of correct answers) performances were measured during single‐, dual‐, and triple‐task conditions. Performances and costs of dual ‐and triple‐ tasking on cycling and cognitive performances were compared between prefrail and frail groups.

Results

Prefrail and frail older adults did not differ in their performance in dual‐tasks; however, frail older adults showed a poorer performance in the triple‐task.

Conclusions

Although future studies need to confirm our observations in larger samples, this pilot study suggests that developing new tools based on triple tasking could be useful for the comprehensive assessment of frailty.
Necroptotic‐susceptible dendritic cells exhibit enhanced antitumor activities in mice
Authors: Zhao Zhanran , Zhang Guangzhi , Sun Yuefang , Winoto Astar
Published: July 2020

Introduction

Priming of tumor‐specific T cells is a key to antitumor immune response and inflammation, in turn, is crucial for proper T‐cell activation. As antigen‐presenting cells can activate T cells, dendritic cells (DCs) loaded with tumor antigens have been used as immunotherapeutics against certain cancer in humans but their efficacy is modest. Necroptosis is a form of programmed cell death that results in the release of inflammatory contents. We previously generated mice with DC deficiency in a negative regulator of necroptosis, Fas‐associated death domain (FADD), and found that these mice suffer from systemic inflammation due to necroptotic DCs. We hypothesize that FADD‐deficient DCs could serve as a better vaccine than wild‐type (WT) DCs against tumors.

Materials and Methods

FADD‐deficient and WT mouse DCs loaded with the relevant tumor peptide were injected onto mice before or after the syngeneic tumor challenge. DC vaccinations were repeated two more times and anti‐PD‐1 antibodies were coinjected in some experiments. Tumor sizes were measured by caliper, and the percentages of tumor‐free mice or mice survived were examined over time. The cytometric analysis was carried out to analyze various immune populations.

Results

In two separate tumor models, we find that mice receiving FADD‐deficient DCs as vaccine rejected tumors significantly better than those receiving a WT DC vaccine. Tumor growth was severely hampered, and survival extended in these mice. More activated CD8 T cells together with elevated cytokines were observed in mice receiving the FADD‐deficient DC vaccine. Furthermore, we observed these effects were potent enough to protect against tumor challenge postinjection and can work in conjunction with anti‐PD‐1 antibodies to reduce the tumor growth.

Conclusions

Necroptotic‐susceptible DCs are better antitumor vaccines than WT DCs in mice. Our findings suggest that necroptosis‐driven inflammation by DCs may be a novel avenue to generating a strong adaptive antitumor response in the clinical setting.
Stock market liberalization, foreign institutional investors, and informational efficiency of stock prices: Evidence from an emerging market
Authors: Li Yijie , Liu Jianghui , Wang Haizhi , Wang Peng
Published: July 2020

This study investigates the effects of investments by qualified foreign institutional investors (QFIIs) on the informational efficiency of stock prices in Chinese A‐share stock markets. Employing a large sample of listed firms from 2004 to 2012, we document a significant and positive relationship between stock price informativeness and stock ownership by foreign institutional investors. We also use the instrument‐variable approach, propensity‐score matching method, as well as an alternative measure of informational efficiency to ensure the robustness of our findings. We document that the effects of foreign ownership on informational efficiency is stronger for firms with lower levels of assets intangibility and in regions with less developed institutions. In addition, we document that the effects of foreign ownership on informational efficiency is more pronounced when QFIIs have better local information and more incentives to monitor.
In vitro and in silico genetic toxicity screening of flavor compounds and other ingredients in tobacco products with emphasis on ENDS
Authors: Hung Pei‐Hsuan , Savidge Matthew , De Mamata , Kang Jueichuan (Connie) , Healy Sheila M. , Valerio Luis G.
Published: July 2020

Electronic nicotine delivery systems (ENDS) are regulated tobacco products and often contain flavor compounds. Given the concern of increased use and the appeal of ENDS by young people, evaluating the potential of flavors to induce DNA damage is important for health hazard identification. In this study, alternative methods were used as prioritization tools to study the genotoxic mode of action (MoA) of 150 flavor compounds. In particular, clastogen‐sensitive (γH2AX and p53) and aneugen‐sensitive (p‐H3 and polyploidy) biomarkers of DNA damage in human TK6 cells were aggregated through a supervised three‐pronged ensemble machine learning prediction model to prioritize chemicals based on genotoxicity. In addition, in silico quantitative structure‐activity relationship (QSAR) models were used to predict genotoxicity and carcinogenic potential. The in vitro assay identified 25 flavors as positive for genotoxicity: 15 clastogenic, eight aneugenic and two with a mixed MoA (clastogenic and aneugenic). Twenty‐three of these 25 flavors predicted to induce DNA damage in vitro are documented in public literature to be in e‐liquid or in the aerosols produced by ENDS products with youth‐appealing flavors and names. QSAR models predicted 46 (31%) of 150 compounds having at least one positive call for mutagenicity, clastogenicity or rodent carcinogenicity, 49 (33%) compounds were predicted negative for all three endpoints, and remaining compounds had no prediction call. The parallel use of these predictive technologies to elucidate MoAs for potential genetic damage, hold utility as a screening strategy. This study is the first high‐content and high‐throughput genotoxicity screening study with an emphasis on flavors in ENDS products.
A systematic review of microRNA expression studies with exposure to bisphenol A
Authors: Farahani Masoumeh , Rezaei‐Tavirani Mostafa , Arjmand Babak
Published: July 2020

Bisphenol A (BPA), as a common industrial component, is generally consumed in the synthesis of polymeric materials. To gain a deeper understanding of the detrimental effects of BPA, BPA‐induced microRNA (miRNA) alterations were investigated. A systematic search was performed in the PubMed, SCOPUS and Web of Science databases to evoke relevant published data up to August 10, 2019. We identified altered miRNAs that have been repeated in at least three studies. Moreover, miRNA homology analysis between human and nonhuman species was performed to determine the toxicity signatures of BPA in human exposure. In addition, to reflect the effects of environmental exposure levels of BPA, the study designs were categorized into two groups, including low and high doses according to the previous definitions. In total, 28 studies encountered our criteria and 17 miRNAs were identified that were differentially expressed in at least three independent studies. Upregulating miR‐146a and downregulating miR‐192, miR‐134, miR‐27b and miR‐324 were found in three studies. MiR‐122 and miR‐29a were upregulated in four studies after BPA exposure, and miR‐21 was upregulated in six studies. The results indicate that BPA at low‐level exposures can also alter miRNA expression in response to toxicity. Finally, the miRNA‐related pathways showed that BPA seriously can affect human health through various cell signaling pathways, which were predictable and consistent with existing studies. Overall, our findings suggest that further studies should be conducted to examine the role of miRNA level changes in human BPA exposure.
Mechanical performance and biocompatibility assessment of Zn‐0.05wt%Mg‐(0.5, 1 wt%) Ag alloys
Authors: Xiao Chi , Su Yun , Zhu Xiaoming , Yu Weiting , Cui Daping , Wei Xiaowei , Zhang Xiuzhi , Li Junlei , Wang Feng , Ren Yuping , Qin Gaowu , Zhao Dewei
Published: July 2020

Zn alloys are emerging as promising degradable biomedical materials due to their tailorable mechanical properties and moderate biodegradable rate, compared with conventional biodegradable metallic materials. Ag, as an effective antibacterial and reinforcing element, was incorporated into Zn‐0.05Mg alloys. In the present work, the effects of the Ag addition on mechanical, cytotoxic, hemolytic, pyrogenic, histological behaviors of the animal were investigated. The compressive yielding strength is enhanced from 198 MPa for Zn‐0.05Mg alloy up to 224 and 234 MPa for Zn‐0.05Mg‐0.5Ag and Zn‐0.05Mg‐1Ag alloys, respectively. When the compressive strain was 65%, the strength of the Zn‐0.05Mg‐1.0Ag alloy reached 833 MPa, which was much higher than that of 721 MPa for Zn‐0.05Mg alloy. The relative growth rate (RGR) for the extracts of Zn‐0.05Mg‐1Ag alloy with the concentrations of 10, 50, and 100% after 5 days incubation reaches 98.5, 95.2, and 94.2%, which are higher than those in extracts of Zn‐0.05Mg‐0.5Ag alloy (98.2, 93.9, 92.1%). The hemolysis rate of the Zn‐0.05Mg alloys with 0.5 and 1 wt% Ag is 2.46 and 2.28%, respectively. The variations of body weight and temperature, postinjection symptoms, pathological morphologies of the visceral organs demonstrate that the alloys are nontoxic according to the toxicity rating standards. Zn‐0.05wt%Mg‐(0.5, 1 wt%) Ag alloys are experimentally safe materials and promising for the future application as biodegradable medical devices.
Vitamin K2 Modulates Vitamin D‐Induced Mechanical Properties of Human 3D Bone Spheroids In Vitro
Authors: Schröder Maria , Riksen Elisabeth Aurstad , He Jianying , Skallerud Bjørn Helge , Møller Mona Elisabeth , Lian Aina‐Mari , Syversen Unni , Reseland Janne Elin
Published: July 2020

Rotational culture promotes primary human osteoblasts (hOBs) to form three‐dimensional (3D) multicellular spheroids with bone tissue‐like structure without any scaffolding material. Cell‐based bone models enable us to investigate the effect of different agents on the mechanical strength of bone. Given that low dietary intake of both vitamin D and K is negatively associated with fracture risk, we aimed to assess the effect of these vitamins in this system. Osteospheres of hOBs were generated with menaquinone‐4 (MK‐4; 10μM) and 25‐hydroxyvitamin D3 [25(OH)D3; 0.01μM], alone and in combination, or without vitamins. The mechanical properties were tested by nanoindentation using a flat‐punch compression method, and the mineralized extracellular bone matrix was characterized by microscopy. The in vitro response of hOBs to MK‐4 and 25(OH)D3 was further evaluated in two‐dimensional (2D) cultures and in the 3D bone constructs applying gene expression analysis and multiplex immunoassays. Mechanical testing revealed that 25(OH)D3 induced a stiffer and MK‐4 a softer or more flexible osteosphere compared with control. Combined vitamin conditions induced the same flexibility as MK‐4 alone. Enhanced levels of periostin (p < 0.001) and altered distribution of collagen type I (COL‐1) were found in osteospheres supplemented with MK‐4. In contrast, 25(OH)D3 reduced COL‐1, both at the mRNA and protein levels, increased alkaline phosphatase, and stimulated mineral deposition in the osteospheres. With the two vitamins in combination, enhanced gene expression of periostin and COL‐1 was seen, as well as extended osteoid formation into the central region and increased mineral deposition all over the area. Moreover, we observed enhanced levels of osteocalcin in 2D and osteopontin in 3D cultures exposed to 25(OH)D3 alone and combined with MK‐4. In conclusion, the two vitamins seem to affect bone mechanical properties differently: vitamin D enhancing stiffness and K2 conveying flexibility to bone. These effects may translate to increased fracture resistance in vivo. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Physical Function and Health‐Related Quality of Life in Adults Treated With Asfotase Alfa for Pediatric‐Onset Hypophosphatasia
Authors: Genest Franca , Rak Dominik , Petryk Anna , Seefried Lothar
Published: July 2020

Hypophosphatasia (HPP) is a rare, inherited, metabolic disease characterized by tissue‐nonspecific alkaline phosphatase deficiency resulting in musculoskeletal and systemic clinical manifestations. This observational study evaluated the effectiveness of enzyme replacement therapy with asfotase alfa on physical function and health‐related quality of life (HRQoL) among adults with pediatric‐onset HPP who received asfotase alfa for 12 months at a single center (ClinicalTrial.gov no.: NCT03418389). Primary outcomes evaluated physical function with the 6‐minute walk test (6MWT), timed up‐and‐go (TUG) test, Short Physical Performance Battery (SPPB), and handheld dynamometry (HHD). Secondary outcome measures included the Lower Extremity Functional Scale (LEFS), pain prevalence/intensity, and pain medication use; HRQoL was evaluated using the 36‐Item Short‐Form Health Survey version 2 (SF‐36v2). Safety data were collected throughout the study. All 14 patients (11 women) had compound heterozygous ALPL gene mutations and ≥1 HPP bone manifestation, including history of ≥1 fracture. Mean (min, max) age was 51 (19 to 78) years. From baseline to 12 months of treatment, median 6MWT distance increased from 267 m to 320 m (n = 13; p = 0.023); median TUG test time improved from 14.4 s to 11.3 s (n = 9; p = 0.008). Specific components of the SPPB also improved significantly: median 4‐m gait speed increased from 0.8 m/s to 1.1 m/s (n = 10; p = 0.007) and median repeated chair‐rise time improved from 22 s to 13 s (n = 9; p = 0.008). LEFS score improved from 24 points to 53 points (n = 10; p = 0.002). Improvements in HHD were not clinically significant. SF‐36v2 Physical Component Score (PCS) improved after 12 months of treatment (n = 9; p = 0.010). Pain level did not change significantly from baseline to 12 months of treatment. There were significant improvements on chair‐rise time and SF‐36v2 PCS by 3 months, and on TUG test time after 6 months. No new safety signals were identified. These results show the real‐world effectiveness of asfotase alfa in improving physical functioning and HRQoL in adults with pediatric‐onset HPP. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
β‐Elemene inhibits 7,12‐dimethylbenz(a)anthracene/12‐O‐tetradecanoylphorbol‐13‐acetate‐induced skin tumorigenesis through suppression of NF‐κB‐associated signaling events in the mouse skin model
Authors: Hu Xing , Wang Liang , Zhang Lili , Zhang Tao
Published: July 2020

β‐Elemene (1‐methyl‐1‐vinyl‐2,4‐diisopropenyl‐cyclohexane), a natural sesquiterpene‐derived curcumae radix, exhibits a variety of pharmacologic properties including anticancer. However, the molecular action of β‐elemene in chemical‐induced skin carcinogenesis remains unclear. Therefore, the present study executes to investigate a possible effect of β‐elemene in the 7,12‐dimethylbenz(a)anthracene (DMBA)/12‐O‐tetradecanoylphorbol‐13‐acetate (TPA)‐promoted skin tumor model. The experimental mice were subjected to execute two‐stage skin carcinogenesis and it has been initiated by the addition of DMBA on the dorsal portion of the mouse skin. One week after, for chemical carcinogen of mice, topical exposure of DMBA has been induced following with TPA (5 nmol) in acetone (200 μL) given weekly twice for 20 weeks respectively. After completion of the experimental period, we noticed that 100% of tumor incidence, histopathological changes, decreased lipid peroxidation (LPO), and decreased antioxidant levels in DMBA/TPA‐promoted skin carcinogenesis. Furthermore, enhanced activity of inflammatory protein markers (nuclear factor [NF]‐κB, tumor necrosis factor‐α, interleukin‐6, cyclooxygenase‐2, and nitric oxide synthase) and cell‐proliferative messenger RNA markers (PCNA, cyclin D1), and increased antiapoptotic protein Bcl‐2; decreased proapoptotic protein marker events Bax and caspase 3 and 9 expressions were noticed in DMBA/TPA promoted skin tissue. In this study, we noticed that β‐elemene noticeably reversed the histopathological changes and antioxidant levels in tumor‐bearing mice. Conversely, β‐elemene effectively inhibits inflammation, cell proliferation events, and enhances proapoptotic factors, by suppression of NF‐κB transcriptional activation in DMBA/TPA animals. Thus, we concluded that β‐elemene prevents DMBA/TPA promoted skin carcinogenesis through its antioxidant and abate inflammation markers and cell‐proliferative markers also activating proapoptotic molecules.
Effects of rhaponticin on retinal oxidative stress and inflammation in diabetes through NRF2/HO‐1/NF‐κB signalling
Authors: Shi Qiang , Cheng Yuhong , Dong Xiaomin , Zhang Ming , Pei Cheng , Zhang Mingzhen
Published: July 2020

Oxidative stress and inflammation have long been considered to be responsible for the development and progression of diabetic retinopathy. On the other hand, rhaponticin (RN) has received scientific attention due to its various pharmacological properties. Keeping all these in view, the present study was performed to investigate the potential protective effects of RN on the retina in diabetic rats. Rats were randomly divided into three groups: control group rats, diabetic group rats, diabetic + RN (20 mg/kg body weight for 28 days through oral route) group rats. RN supplementation to diabetic rats significantly prevent the reduction of final body weight loss, reduced weekly fasting blood glucose levels and HbA1c levels with a significant increase in serum insulin levels. quantitative polymerase chain reaction and immunohistochemical analysis found upregulation of Nrf2, NQO‐1, HO‐1 and upregulation of Keap1 genes and protein distribution along with significantly reduced levels of malondialdehyde and increased activity of superoxide dismutase, catalase and glutathione peroxidase in RN‐treated diabetic rats as compared to diabetic rats. Furthermore, treatment of diabetic rats with RN showed downregulated expression of tumour necrosis factor‐α, matrix metalloproteinase‐2 and upregulated expression of interleukin‐10 (IL‐10) and TIMP‐1 in the retina. RN treatment decreased nuclear factor kappa‐light‐chain‐enhancer of activated B cells distribution and increased IL‐10 protein distribution in the retinae of diabetic rats. In addition, RN treatment ameliorated morphological changes observed in retinae of diabetic rats. Altogether, these results provided clear evidence that treatment of diabetic rats with RN attenuated diabetic retinal changes through its hypoglycaemic, antioxidant and anti‐inflammatory effects.
COVID‐19 pandemic: Students’ perspectives on dental geriatric care and education
Authors: Brondani Mario , Donnelly Leeann
Published: July 2020

Objectives

With the emergence of the COVID‐19 pandemic in Canada and the curtailment of clinical and face‐to‐face university instruction in British Columbia on March 16, 2020, the opportunity arose to explore how third‐ and fourth‐year undergraduate dental students critically considered the impact of the pandemic on education and the practice of dental geriatrics.

Methods

All third‐ and fourth‐year undergraduate dental students within a dental geriatric module were asked to provide a written guided reflection on the question: “In your opinion, what factors make outbreaks (or pandemics) like COVID‐19 relevant to the practice of dental geriatrics?” Reflections were gathered from March 12 to May 8, 2020. Thematic analysis was conducted to identify and interpret patterns of meaning within the reflections by means of an interactive coding process.

Results

A total of 115 reflections, between 291 and 710 words each, were received from 56 third‐year (62.5% male) and 59 fourth‐year (42.6% male) students. Five main themes emerged: experiencing uncertainties, frailty as a moderator, constraints in accessing care, preparedness protocol, and redefining care. The frequency in which the same codes, categories, and themes were assigned varied from 16 to 140 times.

Conclusions

Students’ reflections highlighted the effects of the pandemic, not only on their education but also on frail older adults themselves and the profession of dentistry in general. Further studies are warranted to explore how this curtailment might impact educators’ approaches to geriatric education, as well as the way graduating students will set up their practices and approach geriatric care in the future.
A survey of extracorporeal photopheresis treatment in pediatric patients in the United Kingdom
Authors: Flinn Aisling M. , Macheka Sheba , Slatter Mary , Ewins Anna‐Maria , Gibson Brenda , Lawson Sarah , Tailby Anna , Lucchini Giovanna , New Helen , James Beki , Alfred Arun , Scarisbrick Julia , Gennery Andrew R
Published: July 2020

Extracorporeal photopheresis (ECP) is a second‐line therapy in acute and chronic GVHD and solid organ transplant rejection. We report ECP use in 98 pediatric patients in seven UK centers from 2010 to 2017, the majority treated for aGVHD (73.5%). ECP was safe and well tolerated including in low body weight patients. Most patients were on multiple immunosuppressive therapies prior to ECP; 45.9% were able to reduce or stop immunosuppression with treatment. Complete or partial response was reported in almost 60%. This study supports the need to include ECP treatment data to national transplant databases to provide accurate information regarding service provision, patient outcomes, and safety.
Synthesis and evaluation of novel 1,2,4‐triazolo‐[3,4‐b]‐1,3,4‐thiadiazole tethered chalcone hybrids as potential anticancer agents
Authors: Bujji Sushmitha , Edigi Praveen Kumar , Subhashini Naikal James Prameela
Published: July 2020

A series of novel 1,2,4‐triazolo‐[3,4‐b]‐1,3,4‐thiadiazole tethered chalcone derivatives were designed synthesized by using conventional as well as microwave assisted methods and characterized by 1H NMR, 13C NMR and mass spectral analysis. Microwave assisted synthesis caused an improvement in yield and significant reduction in the reaction time of all the derivatives. All the new synthesized derivatives were further evaluated for their anti‐cancer activity against selected four human cancer cell lines; A549 (Lung), MCF‐7 (Breast), Colo‐205 (Colon) and A2780 (Ovarian). Among the synthesized compounds, 7b, 7c, 7d, 7e, 7g and 7h exhibited potent anticancer activity compared to control drug (etoposide).
Monocytes complexed to platelets differentiate into functionally deficient dendritic cells
Authors: Singh Meera V , Suwunnakorn Sumanun , Simpson Sydney R , Weber Emily A , Singh Vir B , Kalinski Pawel , Maggirwar Sanjay B
Published: July 2020

In addition to their role in hemostasis, platelets store numerous immunoregulatory molecules such as CD40L, TGFβ, β2-microglobulin, and IL-1β and release them upon activation. Previous studies indicate that activated platelets form transient complexes with monocytes, especially in HIV infected individuals and induce a proinflammatory monocyte phenotype. Because monocytes can act as precursors of dendritic cells (DCs) during infection/inflammation as well as for generation of DC-based vaccine therapies, we evaluated the impact of activated platelets on monocyte differentiation into DCs. We observed that in vitro cultured DCs derived from platelet-monocyte complexes (PMCs) exhibit reduced levels of molecules critical to DC function (CD206, dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin, CD80, CD86, CCR7) and reduced antigen uptake capacity. DCs derived from PMCs also showed reduced ability to activate naïve CD4+ and CD8+ T cells, and secrete IL-12p70 in response to CD40L stimulation, resulting in decreased ability to promote type-1 immune responses to HIV antigens. Our results indicate that formation of complexes with activated platelets can suppress the development of functional DCs from such monocytes. Disruption of PMCs in vivo via antiplatelet drugs such as Clopidogrel/Prasugrel or the application of platelet-free monocytes for DCs generation in vitro, may be used to enhance immunization and augment the immune control of HIV.
Dengue virus-activated platelets modulate monocyte immunometabolic response through lipid droplet biogenesis and cytokine signaling
Authors: Barbosa-Lima Giselle , Hottz Eugenio D , de Assis Edson F , Liechocki Sally , Souza Thiago Moreno L , Zimmerman Guy A , Bozza Fernando A , Bozza Patricia T
Published: July 2020

Dengue is characterized as one of the most important arthropod-borne human viral diseases, representing a public health problem. Increased activation of immune cells is involved in the progression of infection to severe forms. Recently, our group demonstrated the contribution of platelet–monocyte interaction to inflammatory responses in dengue, adding to evolving evidence that platelets have inflammatory functions and can regulate different aspects of innate immune responses. Furthermore, stimuli-specific-activated platelets can promote phenotypic changes and metabolic reprogramming in monocytes. Thus, this study aimed to evaluate the roles of dengue virus (DENV)-activated platelets on immunometabolic reprogramming of monocytes in vitro, focusing on lipid droplet (LD) biogenesis. We demonstrated that platelets exposed to DENV in vitro form aggregates with monocytes and signal to LD formation and CXCL8/IL-8, IL-10, CCL2, and PGE2 secretion. Pharmacologic inhibition of LD biogenesis prevents PGE2 secretion, but not CXCL8/IL-8 release, by platelet–monocyte complexes. In exploring the mechanisms involved, we demonstrated that LD formation in monocytes exposed to DENV-activated platelets is partially dependent on platelet-produced MIF. Additionally, LD formation is higher in monocytes, which have platelets adhered on their surface, suggesting that beyond paracrine signaling, platelet adhesion is an important event in platelet-mediated modulation of lipid metabolism in monocytes. Together, our results demonstrate that activated platelets aggregate with monocytes during DENV infection and signal to LD biogenesis and the secretion of inflammatory mediators, which may contribute to dengue immunopathogenesis.
Primary Central Nervous System Lymphoma: Clinical Evaluation of Automated Segmentation on Multiparametric MRI Using Deep Learning
Authors: Pennig Lenhard , Hoyer Ulrike Cornelia Isabel , Goertz Lukas , Shahzad Rahil , Persigehl Thorsten , Thiele Frank , Perkuhn Michael , Ruge Maximilian I. , Kabbasch Christoph , Borggrefe Jan , Caldeira Liliana , Laukamp Kai Roman
Published: July 2020

Background

Precise volumetric assessment of brain tumors is relevant for treatment planning and monitoring. However, manual segmentations are time‐consuming and impeded by intra‐ and interrater variabilities.

Purpose

To investigate the performance of a deep‐learning model (DLM) to automatically detect and segment primary central nervous system lymphoma (PCNSL) on clinical MRI.

Study Type

Retrospective.

Population

Sixty‐nine scans (at initial and/or follow‐up imaging) from 43 patients with PCNSL referred for clinical MRI tumor assessment.

Field Strength/Sequence

T1−/T2‐weighted, T1‐weighted contrast‐enhanced (T1 CE), and FLAIR at 1.0, 1.5, and 3.0T from different vendors and study centers.

Assessment

Fully automated voxelwise segmentation of tumor components was performed using a 3D convolutional neural network (DeepMedic) trained on gliomas (n = 220). DLM segmentations were compared to manual segmentations performed in a 3D voxelwise manner by two readers (radiologist and neurosurgeon; consensus reading) from T1 CE and FLAIR, which served as the reference standard.

Statistical Tests

Dice similarity coefficient (DSC) for comparison of spatial overlap with the reference standard, Pearson's correlation coefficient (r) to assess the relationship between volumetric measurements of segmentations, and Wilcoxon rank‐sum test for comparison of DSCs obtained in initial and follow‐up imaging.

Results

The DLM detected 66 of 69 PCNSL, representing a sensitivity of 95.7%. Compared to the reference standard, DLM achieved good spatial overlap for total tumor volume (TTV, union of tumor volume in T1 CE and FLAIR; average size 77.16 ± 62.4 cm3, median DSC: 0.76) and tumor core (contrast enhancing tumor in T1 CE; average size: 11.67 ± 13.88 cm3, median DSC: 0.73). High volumetric correlation between automated and manual segmentations was observed (TTV: r = 0.88, P < 0.0001; core: r = 0.86, P < 0.0001). Performance of automated segmentations was comparable between pretreatment and follow‐up scans without significant differences (TTV: P = 0.242, core: P = 0.177).

Data Conclusion

In clinical MRI scans, a DLM initially trained on gliomas provides segmentation of PCNSL comparable to manual segmentation, despite its complex and multifaceted appearance. Segmentation performance was high in both initial and follow‐up scans, suggesting its potential for application in longitudinal tumor imaging.

Level of Evidence

3

Technical Efficacy Stage

2
Influence of Nature of Spacer and Hydrocarbon Chain Length on Micellar Encapsulation of Polynuclear Aromatic Hydrocarbons by Carbohydrate Derived Non‐Ionic Gemini Surfactants in Aqueous Ethanol Medium
Authors: Saroj  , Sharma Lalit
Published: July 2020

Gemini surfactants with rigid aromatic spacer ‐CH2‐Ar‐CH2‐: 6,6′‐(N,N′‐di(alkyl)‐1,4‐phenylenedimethylamino)bis(6‐deoxy‐1,2‐O‐isopropylidene‐α‐D‐glucofuranose) and Gemini surfactants with flexible aliphatic spacer ‐(CH2)6‐: 6,6′‐(N,N′‐di(2‐hydroxyalkyl)‐1,6‐hexanediamino)bis(6‐deoxy‐1,2‐O‐isopropylidene‐α‐D‐glucofuranose) have been synthesized, and their micellar properties for encapsulation of polynuclear aromatic hydrocarbons (PAH) viz. fluorene, anthracene, triptycene, and pyrene in aqueous ethanol medium have been studied by means of electronic spectroscopy. The micellar study reveals that nature of spacer and length of hydrocarbon chain of the surfactant has profound effect on micellar encapsulation of PAH. The surfactants with rigid aromatic spacer show greater encapsulation as compared to surfactants with flexible aliphatic spacer. Moreover, the more hydrophobic surfactant, i.e. the surfactant with a longer hydrocarbon chain, shows greater encapsulation toward PAH which are encapsulated in the order of their smaller size.