bluuebunny/crossref_metadata_2025 huggingface dataset:
A comparison between β‐tricalcium phosphate and chitosanpoly‐caprolactone‐based3Dmelt extruded composite scaffolds
Authors: Yoshida Minami , Turner Paul R. , McAdam Christopher John , Ali Mohammed Azam , Cabral Jaydee D.
Published: November 2021

Melt extrusion 3D printing has become an attractive additive manufacturing technology to construct degradable scaffolds as tissue precursors in order to create clinically relevant medical devices. Towards this end, a commonly used synthetic polyester, poly‐caprolactone (PCL), was used to make scaffolds composed of different biomaterial compositions to increase bioactivity using 3D melt pneumatic extrusion technology. Varying ratios of the natural biopolymer, chitosan, or the bioceramic, β‐tricalcium phosphate (TCP) were blended with PCL to fabricate support scaffolds with three‐dimensional (3D) architecture for human bone‐marrow derived mesenchymal stem cell (hBMSC) growth for potential bone regeneration application. In this study, basic printing requirements as well as biomaterial dynamic mechanical (DMA), elemental, and thermogravimetric (TGA) analysis results demonstrate material homogeneity as well as thermal stability. Scaffold morphology and microarchitecture were assessed using scanning electron microscopy (SEM) alongsidein vitroscaffold degradation and biological characterisation. Human BMSC proliferation was assessed using fluorescence imaging, and quantitated via the 3‐(4, 5‐dimethylthiazol‐2‐yl)‐2, 5‐diphenyltetrazolium bromide (MTT) colorimetric assay. Thesein vitrocell viability studies revealed that the highest chitosan concentration blend of 20% favoured the most hBMSC growth, exhibited the most swelling, and showed minimal degradation after 28 days. The 20% TCP blend had the second highest hBMSC growth, exhibited moderate swelling, and the fastest degradation rate. Overall, this study demonstrates the first direct comparison of a natural biopolymer‐based, that is, chitosan, 3D melt extruded PCL composite with that of a bioceramic‐based, that is, β‐TCP, PCL composite and their effects on hBMSC 3D proliferation. 3D melt extruded PCL‐based composite scaffolds methodology offers a straightforward way to print scaffolds with good shape fidelity, interconnected porosities and enhanced bioactivity; and demonstrates their potential use for regenerative, bone repair applications.
New C9‐Monoterpenoid Alkaloids Featuring a Rare Skeleton with Anti‐Inflammatory and Antiviral Activities from Forsythia suspensa
Authors: Li Wei , Sun Li‐Tong , Zhao Lin , Yue Xi‐Dian , Dai Sheng‐Jun
Published: November 2021

Forsyqinlingines C (1) and D (2), two C9‐monoterpenoid alkaloids bearing a rare skeleton, were isolated from the ripe fruits of Forsythia suspensa. Their structures, including absolute configurations, were fully elucidated by extensive spectroscopic data and ECD experiments. The plausible biogenetic pathway for compounds 1 and 2 was also proposed. In vitro, two C9‐monoterpenoid alkaloids showed anti‐inflammatory activity performed by the inhibitory effect on the release of β‐glucuronidase in rat polymorphonuclear leukocytes (PMNs), as well as antiviral activity against influenza A (H1N1) virus and respiratory syncytial virus (RSV).
Homology Modeling and Molecular Dynamics Simulations ofTrypanosoma cruziPhosphodiesterase b1
Authors: Llanos Manuel A. , Alberca Lucas N. , Larrea Salomé C. Vilchez , Schoijet Alejandra C. , Alonso Guillermo D. , Bellera Carolina L. , Gavenet Luciana , Talevi Alan
Published: November 2021

Cyclic nucleotide phosphodiesterases have been implicated in the proliferation, differentiation and osmotic regulation of trypanosomatids; in some trypanosomatid species, they have been validated as molecular targets for the development of new therapeutic agents. Because the experimental structure ofTrypanosoma cruziPDEb1 (TcrPDEb1) has not been solved so far, an homology model of the target was created using the structure ofTrypanosoma bruceiPDEb1 (TbrPDEb1) as a template. The model was refined by extensive enhanced sampling molecular dynamics simulations, and representative snapshots were extracted from the trajectory by combined clustering analysis. This structural ensemble was used to develop a structure‐based docking model of the target. The docking accuracy of the model was validated by redocking and cross‐docking experiments using all available crystal structures of TbrPDEb1, whereas the scoring accuracy was validated through a retrospective screen, using a carefully curated dataset of compounds assayed against TbrPDEb1 and/or TcrPDEb1. Considering the results fromin silicovalidations, the model may be applied in prospective virtual screening campaigns to identify novel hits, as well as to guide the rational design of potent and selective inhibitors targeting this enzyme.
Peppermint Essential Oil and Its Major Volatiles as Protective Agents against Soft Rot Caused by Fusarium sambucinum in Cera Pepper (Capsicum pubescens)
Authors: Pérez‐Vázquez Marco Antonio Kevin , Pacheco‐Hernández Yesenia , Lozoya‐Gloria Edmundo , Mosso‐González Clemente , Ramírez‐García Sergio A. , Romero‐Arenas Omar , Villa‐Ruano Nemesio
Published: November 2021

Cera pepper (Capsicum pubescens) is an exotic fruit considered as a rich source of nutraceuticals with known benefits for human health and also an economic resource for local producers in Mexico. The present investigation reports on the in vitro and in situ antifungal activity of the essential oil from Mentha piperita and its two major volatiles (menthol and menthone) against Fusarium sambucinum, which is a causal agent of soft rot in cera pepper. The application of these components in pepper fruits previously infected with F. sambucinum caused a significant delay (p<0.05) in the emergence of soft rot symptoms. This effect was reflected in the maintenance of pH and fruit firmness during a period of 10 days. The nutrimental content of the fruits (protein, fiber, fat and other proximate parameters) was conserved in the same period of time. The nutraceutical content of these fruits was estimated by the quantification of seven carotenoids (violaxanthin, cis‐violaxanthin, luteoxanthin, antheraxanthin, lutein, zeaxanthin and β‐carotene), ascorbic acid and capsaicinoids (capsaicin and dihydrocapsaicin). According to our results, the essential oil from M. Piperita and its major volatiles exerted a preservative effect on these metabolites. Our findings demonstrated that the essential oil of M. Piperita and its major volatiles represent an ecological alternative for the control of fusariosis caused by F. sambucinum in cera peppers under postharvest conditions.
Effect of the Reliability on the Success of Hydrogen Technologies
Authors: Müller Karsten
Published: November 2021

Reliability of a technology influences several aspects relevant for its long‐term market success. Hydrogen is generally considered to have a realistic chance to play a major role in a future energy system. However, reliability of the respective hydrogen technologies will be an important factor in the question whether they will succeed or not. Reliability engineering offers a number of methodologies to determine reliability of a new technology, find ways of improving it, optimize economics, and identify risks to humans or the environment. In this work, it is demonstrated how reliability influences the cost optimum. Furthermore, it is outlined that the most profitable solution requires a little more investment to avoid loss of revenue due to failing systems needed for the minimum in total costs.
AI in Chemical Engineering – We Are Just at the Beginning
Authors: Bortz Michael , Dadhe Kai , Mitsos Alexander
Published: November 2021

No abstract.
A Photocaged Azidosugar for Light‐Controlled Metabolic Labeling of Cell‐Surface Sialoglycans
Authors: Cheng Bo , Wan Yi , Tang Qi , Du Yifei , Xu Feiyang , Huang Zhimin , Qin Wei , Chen Xing
Published: November 2021

Comprehensive Summary

The photocaging strategy has been widely used for activating biomolecules and hence regulating the underlying biological processes with high temporal and spatial resolution. Herein, we integrate this strategy into metabolic glycan labeling, which enables optically‐controlled metabolic labeling of cell‐surface sialoglycans with azides. N‐Azidoacetylmannosamine (ManNAz) is caged with a 4,5‐dimethoxy‐2‐nitrobenzyl (DMNB) group at the anomeric hydroxyl group to block its cellular metabolism. After feeding to the cells, irradiation with 365 nm UV light or 405 nm visible light cleaves the photocage and generates ManNAz within the cells. ManNAz is metabolically converted to azido sialic acid, which is then incorporated into cell‐surface sialoglycans. We demonstrated spatial and temporal control of this strategy by specifically labeling sialoglycans on a single cell and tracking the metabolism of ManNAz based on light‐triggered pulse‐chase labeling, respectively. The light‐controlled metabolic glycan labeling strategy should facilitate probing of glycosylation in complex biological systems with high spatiotemporal precision.
Phosphonate‐Type Pseudo‐Grafted Precursor: Efficient Surface Modification of Silica
Authors: Ishizaka Yusuke , Matsumoto Kazuhiro , Sato Kazuhiko , Choi Jun‐Chul
Published: November 2021

Surface modification of inorganic metal oxides by grafting phosphonate compounds is a highly useful method for acquiring organic–inorganic hybrid materials. Compared to metal oxides, it is still difficult to modify silica by phosphonates. In this work, we developed an arylphosphonate “pseudo‐grafted precursor” (P‐PGP 1) bearing a disilicate moiety (−OSi(OtBu)2OSi(OtBu)2O−). While conventional grafting methods rely on Si−O−P bond formation, P‐PGP 1 undergoes Si−O−Si bond formation through a substitution reaction on the silicon atoms of the disilicate moiety. Therefore, P‐PGP 1 was grafted onto a silica surface at room temperature with a higher phosphorus content than that obtained with arylphosphonic acid. The characterization of surface species by 31P and 13C CP/MAS NMR analyses and the evaluation of the phosphorus content suggested that the grafting mode of P‐PGP 1 allows efficient surface modification of the silica surface.
Is it possible to determine the optical properties of resin composites with clinical spectrophotometers?
Authors: Soares Karla Danielly Alves , de Bragança Rafaella Mariana , Leal Pollyana Caldeira , Schneider Luis Felipe Jochims , Faria‐e‐Silva André Luis
Published: November 2021

The present study aimed to determine how spectrophotometer type and background blackness affect the optical evaluation of resin composites. Cylindrical specimens were built using one resin composite, provided with translucencies named Effect, Enamel, Body, and Dentin (n = 3). The CIELAB color coordinates were assessed over black and white backgrounds using a handheld spectrophotometer designed for laboratory readings (SP60, X‐Rite) and a spectrophotometer designed for clinical application (Easyshade V5, Vita Zahnfabrik). The black portion of a grayscale target (ColorChecker) and the black trap portion of the calibration reference of the spectrophotometer were used. Color differences between the devices were calculated, as well as the translucency parameter and contrast ratio. Data were analyzed by repeated‐measures ANOVA and linear regressions (α = .05). In general, Easyshade resulted in higher values for all color coordinates than the SP60, irrespective of the background. Easyshade was unable to measure the color of composite Effect over black backgrounds. For other composite translucencies, both spectrophotometers yielded similar values of translucency parameter and contrast ratio, and the blackness of the black background did not affect these results. The highest agreement for the translucency parameter and contrast ratio values was observed for the composite Dentin. High agreement was observed between the two spectrophotometers regarding the translucency parameter and contrast ratio values. However, the clinical spectrophotometer was unable to measure the color of the more translucent composite over a black background and overestimated the color coordinates.
Warm‐night temperature alters paternal allocation strategy in a North temperate‐zone butterfly
Authors: Rosa Elena , Saastamoinen Marjo
Published: November 2021

Warming temperatures are greatly impacting wild organisms across the globe. Some of the negative impacts of climate change can be mitigated behaviorally, for example, by changes in habitat and oviposition site choice. Temperatures are reportedly warming faster at night than during the day, yet studies assessing the impacts of increasing night temperature are rare. We used the Finnish Glanville fritillary butterfly (Melitaea cinxia) as study species and exposed adult butterflies of both sexes to warmer night conditions. Under a seminatural outdoor enclosure, we assessed whether females base their oviposition choices primarily on habitat site characteristics (open, suggestive of dry meadows, versus covered by a coarse canopy, suggestive of pastures) or on plant condition (dry vs. lush), and if their choice is altered by the thermal conditions experienced at night. As exposure to warmer environmental conditions is expected to increase resting metabolic rate and potentially reduce life expectancy, we further assessed the fitness implications of warm‐night temperatures. We found that females prefer open sites for oviposition and that females do not switch their oviposition strategy based on the thermal conditions they experienced at night prior to the reproductive event. Exposure to warm nights did not influence female lifespan, but the egg hatching success of their offspring was reduced. In addition, we found that males exposed to warm nights sired larger clutches with higher hatching rate. As warm‐night exposure reduced male lifespan, this may imply a switch in male resource allocation strategy toward increased offspring quality. The present work adds on to the complex implications of climate warming and highlights the importance of the often‐neglected role of males in shaping offspring performance.
Terrestrial or marine species distribution model: Why not both? A case study with seabirds
Authors: Häkkinen Henry , Petrovan Silviu O. , Sutherland William J. , Pettorelli Nathalie
Published: November 2021

Species reliant on both the terrestrial and marine realms present a challenge for conventional species distribution models (SDMs). For such species, standard single‐realm SDMs may omit key information that could result in decreased model accuracy and performance. Existing approaches to habitat suitability modeling typically do not effectively combine information from multiple realms; this methodological gap can ultimately hamper management efforts for groups such as seabirds, seals, and turtles. This study, for the first time, jointly incorporates both terrestrial information and marine information into a single species distribution model framework. We do this by sampling nearby marine conditions for a given terrestrial point and vice versa using parameters set by each species’ mean maximum foraging distance and then use standard SDM methods to generate habitat suitability predictions; therefore, our method does not rely on post hoc combination of several different models. Using three seabird species with very different ecologies, we investigate whether this new multi‐realm approach can improve our ability to identify suitable habitats for these species. Results show that incorporating terrestrial information into marine SDMs, or vice versa, generally improves model performance, sometimes drastically. However, there is considerable variability between species in the level of improvement as well as in the particular method that produces the most improvement. Our approach provides a repeatable and transparent method to combine information from multiple ecological realms in a single SDM framework. Important advantages over existing solutions include the opportunity to, firstly, easily combine terrestrial and marine information for species that forage large distances inland or out to sea and, secondly, consider interactions between terrestrial and marine variables.
Gene expression and epigenetic responses of the marine Cladoceran, Evadne nordmanni, and the copepod, Acartia clausi, to elevated CO2
Authors: Aluru Neelakanteswar , Fields David M. , Shema Steven , Skiftesvik Anne Berit , Browman Howard I.
Published: November 2021

Characterizing the capacity of marine organisms to adapt to climate change related drivers (e.g., pCO2 and temperature), and the possible rate of this adaptation, is required to assess their resilience (or lack thereof) to these drivers. Several studies have hypothesized that epigenetic markers such as DNA methylation, histone modifications and noncoding RNAs, act as drivers of adaptation in marine organisms, especially corals. However, this hypothesis has not been tested in zooplankton, a keystone organism in marine food webs. The objective of this study is to test the hypothesis that acute ocean acidification (OA) exposure alters DNA methylation in two zooplanktonic species—copepods (Acartia clausii) and cladocerans (Evadne nordmanii). We exposed these two species to near‐future OA conditions (400 and 900 ppm pCO2) for 24 h and assessed transcriptional and DNA methylation patterns using RNA sequencing and Reduced Representation Bisulfite Sequencing (RRBS). OA exposure caused differential expression of genes associated with energy metabolism, cytoskeletal and extracellular matrix functions, hypoxia and one‐carbon metabolism. Similarly, OA exposure also caused altered DNA methylation patterns in both species but the effect of these changes on gene expression and physiological effects remains to be determined. The results from this study form the basis for studies investigating the potential role of epigenetic mechanisms in OA induced phenotypic plasticity and/or adaptive responses in zooplanktonic organisms.
Effects of different types of low‐intensity management on plant‐pollinator interactions in Estonian grasslands
Authors: Motivans Švara Elena , Ştefan Valentin , Sossai Esther , Feldmann Reinart , Aguilon Dianne Joy , Bontsutsnaja Anna , E‐Vojtkó Anna , Kilian Isabel C. , Lang Piret , Mõtlep Marilin , Prangel Elisabeth , Viljur Mari‐Liis , Knight Tiffany M. , Neuenkamp Lena
Published: November 2021

In the face of global pollinator decline, extensively managed grasslands play an important role in supporting stable pollinator communities. However, different types of extensive management may promote particular plant species and thus particular functional traits. As the functional traits of flowering plant species (e.g., flower size and shape) in a habitat help determine the identity and frequency of pollinator visitors, they can also influence the structures of plant−pollinator interaction networks (i.e., pollination networks). The aim of this study was to examine how the type of low‐intensity traditional management influences plant and pollinator composition, the structure of plant−pollinator interactions, and their mediation by floral and insect functional traits. Specifically, we compared mown wooded meadows to grazed alvar pastures in western Estonia. We found that both management types fostered equal diversity of plants and pollinators, and overlapping, though still distinct, plant and pollinator compositions. Wooded meadow pollination networks had significantly higher connectance and specialization, while alvar pasture networks achieved higher interaction diversity at a standardized sampling of interactions. Pollinators with small body sizes and short proboscis lengths were more specialized in their preference for particular plant species and the specialization of individual pollinators was higher in alvar pastures than in wooded meadows. All in all, the two management types promoted diverse plant and pollinator communities, which enabled the development of equally even and nested pollination networks. The same generalist plant and pollinator species were important for the pollination networks of both wooded meadows and alvar pastures; however, they were complemented by management‐specific species, which accounted for differences in network structure. Therefore, the implementation of both management types in the same landscape helps to maintain high species and interaction diversity.
Life in the desert: The impact of geographic and environmental gradients on genetic diversity and population structure of Ivesia webberi
Authors: Borokini Israel T. , Klingler Kelly B. , Peacock Mary M.
Published: November 2021

For range‐restricted species with disjunct populations, it is critical to characterize population genetic structure, gene flow, and factors that influence functional connectivity among populations in order to design effective conservation programs. In this study, we genotyped 314 individuals from 16 extant populations of Ivesia webberi, a United States federally threatened Great Basin Desert using six microsatellite loci. We assessed the effects of Euclidean distance, landscape features, and ecological dissimilarity on the pairwise genetic distance of the sampled populations, while also testing for a potential relationship between I. webberi genetic diversity and diversity in the vegetative communities. The results show low levels of genetic diversity overall (He = 0.200–0.441; Ho = 0.192–0.605) and high genetic differentiation among populations. Genetic diversity was structured along a geographic gradient, congruent with patterns of isolation by distance. Populations near the species’ range core have relatively high genetic diversity, supporting in part a central‐marginal pattern, while also showing some evidence for a metapopulation dynamic. Peripheral populations have lower genetic diversity, significantly higher genetic distances, and higher relatedness. Genotype cluster admixture results suggest a complex dispersal pattern among populations with dispersal direction and distance varying on the landscape. Pairwise genetic distance strongly correlates with elevation, actual evapotranspiration, and summer seasonal precipitation, indicating a role for isolation by environment, which the observed phenological mismatches among the populations also support. The significant correlation between pairwise genetic distance and floristic dissimilarity in the germinated soil seed bank suggests that annual regeneration in the plant communities contribute to the maintenance of genetic diversity in I. webberi.
Aspirin use is associated with increased risk for incident heart failure: a patient‐level pooled analysis
Authors: Mujaj Blerim , Zhang Zhen‐Yu , Yang Wen‐Yi , Thijs Lutgarde , Wei Fang‐Fei , Verhamme Peter , Delles Christian , Butler Javed , Sever Peter , Latini Roberto , GF Cleland John , Zannad Faiez , Staessen Jan A. ,   Heart Omics in Ageing Investigators
Published: November 2021

Aims

Recent trials evaluating the effect of aspirin in the primary prevention of cardiovascular disease showed little or no benefit. However, the role of aspirin on the risk of incident heart failure (HF) remains elusive. This study aimed to evaluate the role of aspirin use on HF incidence in primary and secondary prevention and whether aspirin use increases the risk of incident HF in patients at risk.

Methods and results

Data from 30 827 patients at risk for HF enrolled in six observational studies were analysed [women 33.9%, mean age (±standard deviation) 66.8 ± 9.2 years]. Cardiovascular risk factors and aspirin use were recorded at baseline, and patients were followed up for the first incident of fatal or non‐fatal HF. The association of incident HF with aspirin use was assessed using multivariable‐adjusted proportional hazard regression, which accounted for study and cardiovascular risk factors. Over 5.3 years (median; 5th–95th percentile interval, 2.1–11.7 years), 1330 patients experienced HF. The fully adjusted hazard ratio (HR) associated with aspirin use was 1.26 [95% confidence interval (CI) 1.12–1.41; P ≤ 0.001]. Further, in a propensity‐score‐matched analysis, the HR was 1.26 (95% CI 1.10–1.44; P ≤ 0.001). In 22 690 patients (73.6%) without history of cardiovascular disease, the HR was 1.27 (95% CI 1.10–1.46; P = 0.001).

Conclusions

In patients, at risk, aspirin use was associated with incident HF, independent of other risk factors. In the absence of conclusive trial evidence, our observations suggest that aspirins should be prescribed with caution in patients at risk of HF or having HF.
Effect of two postharvest technologies on the micronutrient profile of cashew kernels from Mozambique
Authors: Uaciquete Americo , Ferreira Neid Ali , Lehnert Katja , Vetter Walter , Sus Nadine , Stuetz Wolfgang
Published: November 2021

The economics involved in processing cashew nuts (Anacardium occidentale) might alter micronutrient profiles and concentrations. We analyzed and evaluated carotenoids, tocopherols, tocotrienols, minerals, fatty acids, and amino acids in (1) cashew kernels with testa recovered from nuts dried with and without the apple, and (2) testa‐free industrial grade baby butts, splits, and white whole kernels using HPLC, ICP‐OES, and GC‐MS techniques. The results indicated that drying cashews with the respective apple slightly decreased the concentration of some carotenoids and total fatty and amino acids, but increased the concentration of iron, magnesium, and total tocotrienols compared with the conventionally (sun‐) dried kernels. We also found high concentrations of carotenoids in the testa‐containing kernels. Among the industrially processed kernel, baby butt grade was associated with lower content of β‐carotene, total tocopherols, and tocotrienols, but with significantly higher concentrations in minerals, fatty acids, and amino acids than in white wholes and split grades. Conventional sun drying of cashew nuts revealed results similar to drying with apples regarding micronutrient concentrations. The high micronutrient content of industrial grade BB is reflected in widespread human consumption and better market value.
New constraints on the tectono‐magmatic evolution of the Tidding‐Mayodia ophiolites, eastern Himalaya, northeast India
Authors: Singh Athokpam Krishnakanta , Dutt Amrita , Nayak Bibhuranjan , Bikramaditya Raj Kumar , Oinam Govind , Thakur Satyajeet S. , Srivastava Rajesh K. , Khogenkumar Shoraisam , Kumar Manoj
Published: November 2021

The Tidding‐Mayodia ophiolites (TMO) exposed along the Lohit and Dibang river valleys in eastern Himalaya that have been considered as the extension of the Indus‐Tsangpo Suture Zone ophiolites are revisited to review their petrogenetic‐tectonic origin. The ophiolites consist of depleted harzburgite and dunite with lesser amounts of mafic rocks (gabbro intrusives, mafic dykes) and carbonates. The serpentinized peridotites consist of antigorite, lizardite, olivine, Cr‐spinel, and bastite with minor sulfide minerals. From SEM‐EDS studies, sulfide minerals were observed to be associated mainly with magnetites. The main sulfide mineral is pentlandite with minor millerite that exists as inclusions inside the pentlandite grains. Elemental mapping of these sulfides shows that they are mainly Ni‐(Co‐)‐bearing sulfides. The olivines are highly forsteritic (Fo = 95–96) while the Cr‐spinels show distinct Cr‐magnetite rims with a chromite core (Cr# = ~93). The serpentinized peridotites have whole‐rock compositions of SiO2 <47 wt% and high MgO (>36.37 wt%) and low Al2O3 (<1.21 wt%), CaO (<0.82 wt%), indicating the depleted nature of the parent rocks. Highly fractionated LREEs as compared to HREEs [(La/Yb)N = 2.62–13.22], and REE and Cr spinel chemistry modelling suggests that the studied peridotites have formed from ~22% partial melting of a depleted spinel lherzolite source which later underwent interactions with a high‐temperature silicate melt that caused enrichment in LREE and Cr of spinels. The parental melt compositions of Cr spinel yield their formation during arc tectonism (Al2O3melt = 6.28–7.65 wt%, FeO/MgO = 1.00–1.33). Furthermore, Mn and Zn concentrations in spinels, the occurrence of Cr magnetite rim in Cr‐spinels, presence of secondary olivine with higher Fo (~98), and occurrence of low‐temperature re‐equilibrated sulfide minerals, indicate that the rocks were subject to low‐temperature metamorphism. Based on this evidence, combined with data from previous studies, a tectonic model has been proposed for the genesis of the studied ophiolites. This model shows that the ophiolites have formed from the entrapment of depleted N‐MORB mantle in the mantle wedge of an intra‐oceanic subduction zone. During the nascent forearc regime, this mantle wedge underwent interactions with high‐temperature melts, which caused changes in their chemistry. Moreover, the rocks underwent interactions with low‐temperature fluids in the mature forearc, which caused the formation of sulfides and metamorphozed these rocks.
Recent Progress in the Synthesis and Potential Applications of Two‐Dimensional Tungsten (Sub)oxides
Authors: Pirker Luka , Višić Bojana
Published: November 2021

While WO3 is one of the most studied metal‐oxides in bulk, it is increasingly gaining interest as a two‐dimensional (2D) material as it exhibits different behaviour compared to bulk. In addition, many substoichiometric WO3–x (0≤x≤1) phases exist both in bulk and 2D form. These Magneli phases have different physical and chemical properties than their WO3 counterparts. By introducing oxygen vacancies, the physical and chemical properties of 2D tungsten (sub)oxide nanomaterials can be further altered. This review focuses on synthesis pathways of 2D tungsten (sub)oxides reported so far, and their subsequent use for various applications. The different stoichiometries and additional oxygen vacancies that appear in these materials, combined with their low thickness and high surface area, make them interesting candidates for gas sensing, catalytic application or in electronic devices.
Non‐ObeseMKRMouse Model of Type 2 Diabetes Reveals Skeletal Alterations in Mineralization and Material Properties
Authors: Tice Matthew J.L. , Bailey Stacyann , Sroga Grażyna E. , Gallagher Emily J. , Vashishth Deepak
Published: November 2021

Obesity is a common comorbidity of type 2 diabetes (T2D). Therefore, increased risk of fragility fractures in T2D is often confounded by the effects of obesity. This study was conducted to elucidate the mechanistic basis by which T2D alone leads to skeletal fragility. We hypothesized that obesity independent T2D would deteriorate bone's material quality by accumulating defects in the mineral matrix and undesired modifications in its organic matrix associated with increased oxidative stress and hyperglycemia. To test this hypothesis, we used 15‐week‐old male non‐obese mice with engineered muscle creatine kinase promoter/human dominant negative insulin growth factor 1 (IGF‐I) receptor (MKR) and FVB/N wild‐type (WT) controls (n = 12/group). MKR mice exhibit reduced insulin production and loss of glycemic control leading to diabetic hyperglycemia, verified by fasting blood glucose measurements (>250 mg/dL), without an increase in body weight. MKR mice showed a significant decrease in femoral radial geometry (cortical area, moment of inertia, cortical thickness, endosteal diameter, and periosteal diameter). Bone mineral density (BMD), as assessed by micro–computed tomography (μCT), remained unchanged; however, the quality of bone mineral was altered. In contrast to controls, MKR mice had significantly increased hydroxyapatite crystal thickness, measured by small‐angle X‐ray scattering, and elongatedc‐axis length of the crystals evaluated by confocal Raman spectroscopy. There was an increase in changes in the organic matrix of MKR mice, associated with enhanced glycoxidation (carboxymethyl‐lysine [CML] and pentosidine) and overall glycation (fluorescent advanced glycation end products), both of which were associated with various measures of bone fragility. Moreover, increased CML formation positively correlated with elongated mineral crystal length, supporting the role of this negatively charged side chain to attract calcium ions, promote growth of hydroxyapatite, and build a physical link between mineral and collagen. Collectively, our results show, for the first time, changes in bone matrix in a non‐obese T2D model in which skeletal fragility is attributable to alterations in the mineral quality and undesired organic matrix modifications. © 2021 The Authors.JBMR Pluspublished by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Myeloid-Specific PTP1B Deficiency Attenuates Inflammation-Induced and Ovariectomy-Induced Bone Loss in Mice by Inhibiting Osteoclastogenesis
Authors: Kim Hyo Jeong , Ryu Ka-Young , Kim Yong-Gun , Kim Myoung Ok , Lee Ji Hye , Song Min-Kyoung , Youn Young-Jin , Pokhrel Nitin Kumar , Kim Sung-Hyun , Kim Jae-Young , Jung Hye-Jin , Kim Woo-Shin , Hong Chang-Won , Kim Hong-Hee , Lee Youngkyun
Published: November 2021

The differentiation and activity of bone-resorbing osteoclasts are tightly regulated to maintain the homeostasis of healthy bones. In this study, the role of protein tyrosine phosphatase 1B (PTP1B) during osteoclastogenesis was studied in myeloid-specific Ptpn1-deficient (conditional knockout [cKO]) mice. The mRNA and protein expression of PTP1B increased during the formation of mature osteoclasts from mouse bone macrophages on stimulation with macrophage-colony stimulating factor (M-CSF) and receptor activator of nuclear factor κB ligand (RANKL). The Ptpn1 cKO mice exhibited increased femoral trabecular bone volume with a decreased number and activity of osteoclasts compared with control mice. The in vitro culture of osteoclast precursors corroborated the inhibition of osteoclastogenesis in cKO cells compared with control, with concomitantly decreased RANKL-dependent proliferation, lower osteoclast marker gene expression, reduced nuclear expression of nuclear factor of activated T cells cytoplasmic 1 (NFATc1), diminished intracellular Ca2+ oscillations, and increased phosphorylation of proto-oncogene tyrosine-protein kinase Src on inhibitory tyrosine residue. In a ligature-induced periodontitis model, Ptpn1 cKO mice exhibited attenuated osteoclastogenesis and alveolar bone loss following the induction of inflammation. The Ptpn1-deficient mice were similarly protected from ovariectomy-induced bone loss compared with control mice. These results provide a novel regulatory role of PTP1B in osteoclastogenesis and suggest a potential as a therapeutic target for bone-lytic diseases. © 2021 American Society for Bone and Mineral Research (ASBMR).
Measurement of synovium and serum dual specificity phosphatase 22 level: Their inter‐correlation and potency as biomarkers in rheumatoid arthritis
Authors: Qian Chen , Chen Jie , Xu Xiaopeng , Liu Qingyang , Gu Minhong , Lu Sheng , Bai Hongxia , Wang Qiubo , Xue Mingyu
Published: November 2021

Background

Dual specificity phosphatase 22 (DUSP22), also named as Jun N‐terminal kinase pathway associated phosphatase recently, is reported to be closely engaged in immune and inflammation regulation. This study aimed to investigate the interaction between synovium DUSP22 and serum DUSP22 levels and to explore their correlation with rheumatoid arthritis (RA) risk, inflammation, and disease activity.

Methods

Synovium and serum samples from 42 RA patients with knee involvement underwent arthroscopy, and 20 knee trauma patients were collected. Besides, serum samples from 40 healthy controls were also obtained. Synovium DUSP22 expression was detected by reverse transcription quantitative polymerase chain reaction, while serum DUSP22 level was detected by enzyme‐linked immunosorbent assay.

Results

Synovium DUSP22 level was greatly decreased in RA patients compared to trauma controls (p < 0.001), and it was negatively correlated with tender joint count (TJC) (r = −0.318, p = 0.040), C‐reactive protein (CRP) (r = −0.330, p = 0.033), and Lysholm score (r = −0.423, p = 0.005) in RA patients. Serum DUSP22 level was lowest in RA patients, followed by trauma controls, then highest in healthy controls (p < 0.001). Serum DUSP22 level was negatively associated with TJC (r = −0.438, p = 0.004), swollen joint count (SJC) (r = −0.372, p = 0.015), CRP (r = −0.391, p = 0.011), and disease activity score in 28 joints (DAS28ESR) score (r = −0.406, p = 0.008), and it increased after treatment (p = 0.001) in RA patients. In addition, serum DUSP22 level positively related to synovium DUSP22 level in RA patients (r = 0.394, p = 0.010).

Conclusion

Synovium and serum DUSP22 are intercorrelated and insufficiently expressed in RA patients; meanwhile, their deficiency correlates with increased systemic inflammation, disease activity, and joint dysfunction.
Combination of artificial intelligence‐based endoscopy and miR148a methylation for gastric indefinite dysplasia diagnosis
Authors: Watanabe Yoshiyuki , Oikawa Ritsuko , Agawa Shuhei , Matsuo Yasumasa , Oda Ichiro , Futagami Seiji , Yamamoto Hiroyuki , Tada Tomohiro , Itoh Fumio
Published: November 2021

Background and Aim

Gastrointestinal endoscopy and biopsy‐based pathological findings are needed to diagnose early gastric cancer. However, the information of biopsy specimen is limited because of the topical procedure; therefore, pathology doctors sometimes diagnose as gastric indefinite for dysplasia (GIN).

Methods

We compared the accuracy of physician‐performed endoscopy (trainee, n = 3; specialists, n = 3), artificial intelligence (AI)‐based endoscopy, and/or molecular markers (DNA methylation: BARHL2, MINT31, TET1, miR‐148a, miR‐124a‐3, NKX6‐1; mutations: TP53; and microsatellite instability) in diagnosing GIN lesions. We enrolled 24,388 patients who underwent endoscopy, and 71 patients were diagnosed with GIN lesions. Thirty‐two cases of endoscopic submucosal dissection (ESD) in 71 GIN lesions and 32 endoscopically resected tissues were assessed by endoscopists, AI, and molecular markers to identify benign or malignant lesions.

Results

The board‐certified endoscopic physicians group showed the highest accuracy in the receiver operative characteristic curve (area under the curve [AUC]: 0.931), followed by a combination of AI and miR148a DNA methylation (AUC: 0.825), and finally trainee endoscopists (AUC: 0.588).

Conclusion

AI with miR148s DNA methylation‐based diagnosis is a potential modality for diagnosing GIN.
iTRAQ‐based proteomic analysis of differentially expressed proteins in sera of seronegative and seropositive rheumatoid arthritis patients
Authors: He Yujue , Lin Junyu , Tang Jifeng , Yu Ziqing , Ou Qishui , Lin Jinpiao
Published: November 2021

Objective

The diagnosis of seronegative rheumatoid arthritis (SNRA) is often difficult due to the unavailability of reliable laboratory markers. The aim of this study was to identify differentially expressed proteins in sera of SNRA, seropositive RA (SPRA), and healthy donors (HD).

Methods

A total of 32 seropositive RA patients, 32 SNRA patients, and 35 HD were enrolled in our study. Differentially expressed proteins between 3 groups were identified via isobaric tags for relative and absolute quantitation (iTRAQ)‐based proteomic analysis, and an ELISA test was used for the validation test. Correlation analysis was conducted by GraphPad Prism.

Results

Using iTRAQ quantitative proteomics, we identified 14 proteins were significantly different between SPRA and SNRA, including 4 upregulated proteins and 10 downregulated proteins. Four differentially expressed proteins were validated by ELISA test, and the results showed that SAA1 protein was significantly higher in SPRA and SNRA patients compared with HD, and PSME1 was elevated in SPRA patients. What's more, SAA1 was increased in the anti‐CCP or RF high‐level group in RA patients, and PSME1 was increased in the RF high‐level group. Alternatively, SAA1 was positively correlated with inflammation indicators in RA patients, while PSME1 showed no correlation with inflammation indicators.

Conclusions

iTRAQ proteomic approaches revealed variations in serum protein composition among SPRA patients, SNRA patients, and HD and provided new idea for advanced diagnostic methods and precision treatment of RA.
The best mirror of the students' longitudinal performance: Portfolio or structured oral exam assessment at clerkship?
Authors: Isbej Lorena , Cantarutti Cynthia , Fuentes‐Cimma Javiera , Fuentes‐López Eduardo , Montenegro Uriel , Ortuño Duniel , Oyarzo Natacha , Véliz Claudia , Riquelme Arnoldo
Published: November 2021

Objective

This study aimed to compare the strength of association (i.e., explained variability) of the cumulative grade point average (GPA) with the grades obtained in the clerkship portfolio and the final structured oral exam by dental students.

Methods

A prospective longitudinal study was designed to analyze quantitative data from three cohorts of dental school students. Univariate and multivariate linear regression models were built to evaluate the association between the students' cumulative GPA with the grades obtained in their clerkship portfolio and the final structured oral exam.

Results

In total, 171 students in the last year of the undergraduate program were considered (76% women, age average 24.8 ± 1.6 years). The dental students' grades of both portfolio and structured oral exam were significantly associated with the GPA score but with different strengths of association. The clerkship portfolio was more strongly associated with cumulative GPA than the structured oral exam (R2 = 19.6% versus R2 = 7.6%). On the opposite, the association between the structured oral exam and GPA can be interpreted as a lower precision in its practical significance and thus reflecting different concurrent validity.

Conclusions

Considering the results of this study, it could probably incline the balance toward the portfolio because it may be closer to a programmatic assessment model, with timely feedback, development of metacognition, and the achievement of formative process measurement rather than evidence of a single instance of examination.
New indications and platforms for CAR‐T therapy in lymphomas beyond DLBCL
Authors: Iqbal Madiha , Savani Bipin N , Hamadani Mehdi
Published: November 2021

CD19‐directed chimeric antigen receptor T‐cell therapy (CAR‐T) represents a significant advancement for patients with relapsed/refractory large B‐cell lymphoma (LBCL). Long‐term follow‐up confirms durable remissions in nearly half of the patients, a population that was previously estimated to have a median survival of around 6 months with standard salvage therapy. This initial success of CAR‐T has led to significant expansion across other lymphoma histologies resulting in the recent regulatory approval of CAR‐T in mantle cell lymphoma and follicular lymphoma. Additionally, multiple novel platforms of CAR‐T therapy are under development to improve efficacy and limit toxicity such dual antigen targeting, allogeneic and natural killer CARs. In this review, we focus on the new indications of CAR‐T in lymphomas beyond LBCL as well as emerging platforms of CAR‐T therapy.
A study of the evolution of the third COVID‐19 pandemic wave in the Athens metropolitan area, Greece, through two cross‐sectional seroepidemiological surveys: March, June 2021
Authors: Maltezou Helena C. , Krumbholz Bettina , Mavrouli Maria , Tseroni Maria , Gamaletsou Maria N. , Botsa Evanthia , Anastassopoulou Cleo , Gikas Aristofanis , Fournarakou Evanthia , Kavieri Maria , Koureli Aikaterini , Mandilara Dionysia , Marinopoulou Aikaterini , Theodorikakou Argyro , Tsiahris Panagiotis , Zarzali Anastasia , Pournaras Spyridon , Lourida Athanasia , Elefsiniotis Ioannis , Vrioni Georgia , Sipsas Nikolaos V. , Tsakris Athanasios
Published: November 2021

We studied the third coronavirus disease 2019 (COVID‐19) pandemic wave in Athens metropolitan area (3 738 901 inhabitants) through two seroepidemiological surveys. Persons presenting in 12 healthcare facilities across Athens in March and June 2021 were studied (764 and 901, respectively). Immunoglobulin G antibodies against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) spike protein were measured by a chemiluminescent microparticle immunoassay. In March the seroprevalence rate was 11.6%, meaning that 435 208 residents of Athens had evidence of immunity. The respective values in June were 55.7% and 2 082 568 residents. The highest seroprevalence rates attributed to SARS‐CoV‐2 infection were recorded in persons <18 years (16.3% in March and 31.6% in June), while immunity was mainly vaccine‐induced in persons 18–64 years and >65 years. Infection‐attributed immunity also increased in older‐age groups. Wide ranges in seroprevalence rates were noted across areas in March and June. The highest seroprevalence rates were recorded in Piraeus (47.2%) and West Attica (37.5%). However, the highest increase (>5 times) occurred in Piraeus and the South Section of Athens, which are among the most densely populated areas in Athens. In both study periods, history of COVID‐19 or febrile episode, and having a cohabitant with COVID‐19 were associated with increased risk for seropositivity among unvaccinated persons (p values <0.001 for all). Residing in Piraeus, the South Section or West Attica was associated with increased risk for seropositivity in June (p values <0.001). Wide heterogeneity in seroprevalence rates was found across areas in Athens, which is mainly attributed to population density. The impact of population mobility and socioeconomic status should be explored.
Activation of canonical Wnt signaling accelerates intramembranous bone regeneration in male mice
Authors: Ko Frank C. , Moran Meghan M. , Ross Ryan D. , Sumner D. Rick
Published: November 2021

Canonical Wnt signaling plays an important role in skeletal development, homeostasis, and both endochondral and intramembranous repair. While studies have demonstrated that the inhibition of Wnt signaling impairs intramembranous bone regeneration, how its activation affects intramembranous bone regeneration has been underexplored. Therefore, we sought to determine the effects of activation of canonical Wnt signaling on intramembranous bone regeneration by using the well‐established marrow ablation model. We hypothesized that mice with a mutation in the Wnt ligand coreceptor gene Lrp5 would have accelerated intramembranous bone regeneration. Male and female wild‐type and Lrp5‐mutant mice underwent unilateral femoral bone marrow ablation surgery in the right femur at 4 weeks of age. Both the left intact and right operated femurs were assessed at Days 3, 5, 7, 10, and 14. The intact femur of Lrp5 mutant mice of both sexes had higher bone mass than wild‐type littermates, although to a greater degree in males than females. Overall, the regenerated bone volume in Lrp5 mutant male mice was 1.8‐fold higher than that of littermate controls, whereas no changes were observed between female Lrp5 mutant and littermate control mice. In addition, the rate of intramembranous bone regeneration (from Day 3 to Day 7) was higher in Lrp5 mutant male mice compared to their same‐sex littermate controls with no difference in the females. Thus, activation of canonical Wnt signaling increases bone mass in intact bones of both sexes, but accelerates intramembranous bone regeneration following an injury challenge only in male mice.