bluuebunny/crossref_metadata_2025 huggingface dataset:
Design Approach of Lifetime Extending Thermally Activated Delayed Fluorescence Sensitizers for Highly Efficient Fluorescence Devices
Authors: Yoon Sung Joon , Kim Ji Han , Chung Won Jae , Lee Jun Yeob
Published: November 2020

In this work, a design approach of three thermally activated delayed fluorescence (TADF) emitters to extend the device lifetime of the TADF sensitized fluorescent devices was studied. Three TADF materials, 5‐{4,6‐bis[4‐(tert‐butyl)phenyl]‐1,3,5‐triazin‐2‐yl}‐2‐(10,15‐diphenyl‐10,15‐dihydro‐5H‐diindolo[3,2‐a:3′,2′‐c]carbazol‐5‐yl)benzonitrile (tTCNTruX), 4‐[3‐cyano‐4‐(10,15‐diphenyl‐10,15‐dihydro‐5H‐diindolo[3,2‐a:3′,2′‐c]carbazol‐5‐yl)phenyl]‐2,6‐diphenylpyrimidine‐5‐carbonitrile (PCNTruX) and 4‐(4‐{10,15‐bis[4‐(tert‐butyl)phenyl]‐10,15‐dihydro‐5H‐diindolo[3,2‐a:3′,2′‐c]carbazol‐5‐yl}‐3‐cyanophenyl)‐2,6‐diphenylpyrimidine‐5‐carbonitrile (PCNtTruX), were synthesized as sensitizers for TADF‐sensitized fluorescent organic light‐emitting diodes. The two tTCNTruX and PCNtTruX TADF emitters were designed to have Dexter energy transfer with blocking groups either in the donor or acceptor unit of the donor–acceptor‐type TADF sensitizer. The TADF materials showed small singlet–triplet energy splitting and a high reverse intersystem crossing (RISC) rate for effective sensitization of the fluorescent emission of the fluorescent emitter. tTCNTruX‐ and PCNtTruX‐sensitized fluorescent devices showed maximum external quantum efficiencies (EQEs) of 17.7 % and 11.5 % in the yellow and red devices, respectively, which were higher than those of TADF‐sensitized devices with the corresponding TADF sensitizer without a blocking group. Moreover, the device lifetime was also extended by employing the tTCNTruX and PCNtTruX sensitizers. This work demonstrated that the tTCNTruX and PCNtTruX sensitizers are effective to improve the maximum EQE and device lifetime of TADF‐sensitized fluorescent devices.
Fluorescence Turn‐off Magnetic Fluorinated Graphene Composite with High NIR Absorption for Targeted Drug Delivery
Authors: Wang Dandan , Zhang Yuanyuan , Zhai Mingzhu , Huang Yan , Li Hui , Liu Xicheng , Gong Peiwei , Liu Zhe , You Jinmao
Published: November 2020

Although fluorinated graphene/Fe3O4 composites exhibit a unique structure and chemical surface, and thus hold great potential in many fields, their effective synthesis has remained a headache because of poor dispersity and easy aggregation behavior. Herein, we report a novel method to prepare hyaluronic acid (HA)‐modified fluorinated graphene with a well‐defined structure and good solubility in various media, and this then allowed us for the first time to controllably deposit magnetic Fe3O4 nanoparticles onto the sheets with designed ratio and contents. This strategy further guaranteed a multifunctional composite that possessed HA and magnetism‐induced dual‐targeting effect towards cancer cells and high near‐infrared absorption for photothermal therapy (PTT). Moreover, this composite also showed an effective turn‐off fluorescence effect for the anticancer drug doxorubicin, allowing us to visually monitor the drug loading procedure. Anticancer experiments indicated that such a successful combination of PTT and chemotherapy with special selectivity toward cancer cells exhibited a much better therapeutic effect than single therapy.
Context‐aware resource management and alternative pricing model to improve enterprise cloud adoption
Authors: Balaji Mahesh , Ch Aswani Kumar
Published: November 2020

Existing Cloud resource management approaches favor Cloud service providers because of their data‐center origin. The onus of efficiently managing the resources is on the end‐user. Present provisioning/deprovisioning methods and the pricing model could be modified to ensure that the end‐user reaps the benefits. The current study proposes a context‐aware Cloud resource management approach based on a workload‐type provisioning and a just‐in‐time deprovisioning design. Furthermore, it also recommends an alternative pricing model. The design intends to provision/deprovision individual resources like CPU, memory, and so on, according to the workload‐type rather than instance‐type as done in existing Cloud resource management approaches. The proposed approach was commissioned on a private lab infrastructure and several experiments were conducted. It was observed that the proposed approach was able to detect sample workload types with an average sensitivity of 82% and specificity of 76%. The average cost of the proposed approach was found to be 20% less than the present approach.
An improved agglomerative hierarchical clustering anomaly detection method for scientific data
Authors: Shi Peng , Zhao Zhen , Zhong Huaqiang , Shen Hangyu , Ding Lianhong
Published: November 2020

Anomaly detection tries to find out the data that disobeys the rule of majority data or expected patterns. The traditional hierarchical clustering algorithms have been adopted to detect anomaly, but have the disadvantages of low effectiveness and unstability. So we propose an improved agglomerative hierarchical clustering method for anomaly detection. It dynamically adjusts the optimum clustering number according to the self‐defined criterion to save the trouble of manually picking clustering number, and determines the optimum clustering distance mode according to cophenetic correlation coefficient to reduce the procedure of manually testing the suitable distance mode in each iteration. The performances of proposed method are verified on tensile test, HTRU2 and credit card dataset. Compared with the traditional methods, our method possesses the most comprehensive performance (the highest F‐measure with less iterations), which shows effectiveness of anomaly detection. And compared with the traditional methods (single, complete, average, and centroid mode), our method achieves the best performance on tensile test and HTRU2 dataset, showing stronger generalization. Compared with other methods (Decision + Gradient Boosted Tree, Decision Trees + Decision Stump, etc) on credit card dataset, our method obtains similar accuracy, and ranks in the top level in the aspect of sensitivity.
Evaluating the morphological features of the lateral pterygoid insertion into the medial surface of the condylar process
Authors: Sritara Sasin , Tsutsumi Masahiro , Fukino Keiko , Matsumoto Yoshiro , Ono Takashi , Akita Keiichi
Published: November 2020

Objective

The lateral pterygoid is vital in coordinating multidimensional jaw movements. Since a vector in three‐dimensional (3D) space is defined by two 3D points, the role of the lateral pterygoid in 3D jaw movements is defined by its origin and insertion. Reportedly, the lateral pterygoid is inserted into not only the pterygoid fovea but also into the medial surface of the condylar process. The objective was to investigate the morphological features of the region of the lateral pterygoid that inserted into the medial surface of the condylar process.

Material and Methods

Ten head halves of seven cadaveric donors were analyzed. In all specimens, the insertion area on the medial surface of the condylar process was measured based on microcomputed tomography images. Muscle fibers were separated into ≥50 small bundles, and positional relationships between the origins and insertions were investigated.

Results

Overall, 28.8 ± 5.0% of the insertion area of the lateral pterygoid was situated on the medial surface of the condylar process. Moreover, muscle fiber arrangement revealed that origins of the muscle bundles inserting into the medial surface in seven specimens posteriorly occupied the lateral plate of the pterygoid process longitudinally, whereas those in three specimens mainly occupied the posteroinferior portion.

Conclusions

Muscle bundle inserting on the medial surface of the condylar process had a broad insertion area and a distinct origin on the posterior region of the lateral plate of the pterygoid process. This muscle bundle could act as one of the significant subunits within the lateral pterygoid. Therefore, anatomical coordination mechanisms underlying jaw movement cannot be elucidated without considering this subunit.
Cutaneous metastasis in a case of Wilm's tumor diagnosed on cytology ‐ A rare case report
Authors: T Paruvathavarthini , Stephen Norton , A Pradeep , Gochhait Debasis , Bh Srinivas , Siddaraju Neeliah , Raj Joe Vimal
Published: November 2020

A 12‐year‐old male child presented with complaints of a slow growing swelling in the right parasternal region noticed since one month. On examination, the lump was 2 × 2 cm firm, mobile nontender located in the subcutaneous plane which was also confirmed radiologically. Fine needle aspiration cytology was attempted showed small to medium sized monotonous round cell morphology, nuclear molding and mitotic figures were frequent. Few cells exhibiting rosettoid arrangement. No definite epithelial or mesenchymal component was evident. No glio‐fibrillary matrix or lymphoglandular bodies were evident in the smears. Based on morphology, a small round cell tumor was considered with possibilities of Wilm's tumor and Ewing's family of tumor. Based on morphological differentials ICC was requested, tumor cells were positive for strong nuclear WT1 staining while CK and FLI1 were negative. The cytomorphology along with the ICC confirmed the diagnosis of metastatic wilm's tumor. Seven years back, patient had a history of nephrectomy, which on histopathology was reported as triphasic Wilms tumor with favorable histology. Generally Wilm's tumor recurs within 2 years of diagnosis. Late recurrence in Wilm's tumor is rare with only a handful of case reports. Common sites for metastasis include lung, liver, contralateral kidney. Cutaneous metastasis is very uncommon, early detection of which with helps in therapeutic and prognostic decisions. The interesting aspect of this article is cytological detection of cutaneous metastasis of late recurrence Wilm's tumor, which is extremely rare to occur.
Extraction of Oat Lipids and Phospholipids Using Subcritical Propane and Dimethyl Ether: Experimental Data and Modeling
Authors: Li Yuntong , Obadi Mohammed , Qi Yajing , shi Jiachen , Liu Shuyi , Sun Jun , Chen Zhongwei , Xu Bin
Published: November 2020

Effects of subcritical solvents (propane, dimethyl ether (DME), and their 1:1 mixed solvents) and extraction temperatures (30 to 60 °C) on oat lipids and phospholipid extraction are investigated using the Patricelli kinetic model and thermodynamic analysis. The mass‐transfer coefficient (k1) of the washing stage is approximately ten times higher than the diffusion stage under different solvents and temperature conditions. Compared with the subcritical propane and mixed solvents, the maximum equilibrium yield of oat lipids and phospholipids are obtained using subcritical DME. With increased extraction temperature from 30 to 60 °C, the equilibrium yield of phospholipids increases, whereas the equilibrium yield of lipids increases to 5.30% at 40 °C and then decreases. The enthalpy and entropy changes for phospholipid extraction are higher than those for lipid extraction. The Gibbs free energy for phospholipid extraction rapidly decreases with increased extraction temperature. A loose endosperm of oat grain is observed, and the concentration of lipids in the bran layer is higher than in the endosperm. In conclusion, kinetic and thermodynamic analyses statistically prove that DME is more effective than propane and mixes solvents for extracting lipids and phospholipids from oat flakes, and that phospholipid extraction strongly depends on temperature.

Practical Application: The removal of lipids and phospholipids benefits oat‐product processing and storage. However, traditional industrial n‐hexane extraction usually requires a high‐temperature process for solute–solvent separation, which may result in low quality of the meal. Subcritical‐fluid extraction is a rising technology for lipid and phospholipid extraction. The yields of lipids and phospholipids using subcritical dimethyl ether (DME) is higher than those propane and its mixed solvents. The temperature dependence of phospholipid extraction is more active than that of lipid extraction. Thus, use of subcritical DME is a promising lipid‐extraction technique to obtain solvent­free oat oil and high‐quality defatted oat flour with potential application in the oat‐processing industry.
Identity confirmation of anthocyanins in berries by LC–DAD–IM‐QTOFMS
Authors: Delgado‐Povedano María del Mar , de Villiers André , Hann Stephan , Causon Tim
Published: November 2020

Rugged analytical methods for the screening and identity confirmation of anthocyanins require a dedicated sample preparation, chromatographic setup, and the reliable generation of multiple identification points to confirm identity against the wide range of phenolic compounds typically present in food, beverage, and plant material samples. To this end, combinations of spectroscopic and mass spectrometric detection are frequently employed for this application to provide higher confidence in the absence of authentic standards. In the present work, low‐field drift tube ion mobility (DTIM) separation is evaluated for this task using a LC–DAD–DTIM–QTOFMS method. DTIM‐MS allows accurate determination of collision cross sections (DTCCS) for all analysed compounds as well as a precise alignment tool for reconciling fragment and precursor ions in data independent acquisition mode. The presented approach thereby allows for an anthocyanin screening method taking true advantage of all dimensions of the analytical platform: relative retention (RPLC), UV/VIS absorption spectrum, accurate mass, DTCCSN2, and confirmed high‐resolution fragment ions. From the analysis of authentic standards and several berry samples primarily from the Vaccinium genus, Level 1 confirmation data for six anthocyanins from the cyanidin family, and Level 2 confirmation for a further 29 anthocyanins confirmed in berry samples is provided. The method and accompanying dataset provided as part of this work provides a means to develop anthocyanin screening methods using the ion mobility dimension as an additional alignment and filtering parameter in data independent analysis acquisition across any LC–IM–MS platform.
Estimating the impact of the mattress fire safety Standard 16 CFR Part 1633 on bed fire outcomes
Authors: Gilbert Stanley W. , Butry David T. , Davis Rick D. , Gann Richard G.
Published: November 2020

Beds are a prevalent combustible in fatal fires in the United States effective 1 July 2007, the US Consumer Product Safety Commission promulgated a standard to severely reduce the heat release rate and the early heat output from mattresses and foundations when ignited by a flaming ignition source. This study estimates the Standard's success over its first decade using fire incidence, US population, and mattress sales data. The technique mitigates the influence of some exogenous factors that might have changed during this decade. The Standard is accomplishing its purpose, preventing approximately 65 fatalities (out of an estimated 95 fatalities in 2002‐2005) from bed fires annually during 2015‐2016, although not all pre‐Standard mattresses had yet been replaced. Compared to residential upholstered furniture fires, which were not affected by the Standard, the numbers of bed fires decreased by 12%, injuries by 34%, and deaths by 82% between 2005‐2006 and 2015‐2016. Per bed fire, injuries decreased by 25% and fatalities decreased by 67%, indicating that the severity of bed fires is being reduced.
Effects of sorghum rice and black rice on genes associated with cholesterol metabolism in hypercholesterolemic mice liver and intestine
Authors: Liu Haiying , Huang Lu , Pei Xinli
Published: November 2020

The effects of different proportions of dietary sorghum rice and black rice on the expression of genes related to cholesterol metabolism in mice liver, intestine, and the characteristics of the small intestinal microbiota were investigated. Six types of diets were used to feed C57BL/6 mice: AIN‐93M standard diet, high‐cholesterol model diet, high‐cholesterol and low‐dose sorghum grain or black rice diet, and high‐cholesterol and high‐dose sorghum grain or black rice diet. The results showed that black rice or sorghum grain diets had no effect on the serum TC, LDL‐C levels in the hypercholesterolemic mice, whereas these diets decreased serum TG level, and black rice diets increased serum HDL‐C level. The diets containing black rice and sorghum grain had no effect on liver TC, TG, HDL‐C levels. However, these diets decreased LDL‐C levels significantly except high dose of black rice. The black rice or sorghum grain diets reduced the expression of the genes encoding liver 3‐hydroxyl‐3‐methyl‐glutarate monoacyl coenzyme A reductase (HMG‐CoA‐R) and increased the expression of SREBP‐2, thereby partially inhibiting the synthesis of cholesterol in liver. The diets containing different proportions of black rice and a low proportion of sorghum grain reduced the expression level of Niemann–Pick type C 1 like 1 (NPC1L1) mRNA and increased the mRNA level of the ATP‐binding cassette transporters, ABCG5/ABCG8, in the small intestine, thereby reducing cholesterol absorption. A diet containing a low proportion of black rice promoted the expression of ABCA1 mRNA and increased the expression of high‐density lipoprotein (HDL) mRNA, thereby promoting reverse cholesterol transport. Black rice diets significantly increased the relative abundances of microbiota in the small intestine and maintained biodiversity, while sorghum grain had no positive effect on the abundance of microbiota.
Tectonic setting and provenance of Early Cretaceous strata in the footwall of Main Central Thrust, Eastern Nepal: Implications for the archipelago palaeogeography of the Neo‐Tethys
Authors: Li Rui , Ao Songjian , Xiao Wenjiao , Windley Brian F. , Zhan Mingguo , Huang Peng , Bhandari Saunak
Published: November 2020

The Early Cretaceous palaeogeography prior to the India‐Asia collision is still controversial. There are two end‐member models – an integrated passive margin versus an archipelago. Here, we report zircon U–Pb ages, Hf, and whole‐rock Nd isotopes of newly defined Cretaceous mica schists from the Main Central Thrust to constrain the Early Cretaceous palaeogeography of the Himalaya. The mica schists have Early Cretaceous zircons with εHf(t) values of −21.1 to −9.2. The mica schists are characterized by TDMC values of 1.8–2.5 Ga and whole‐rock εNd(0) value of −24.0. These features imply that these zircons generated from partial melting of lower crust as a result of an extension in some older continental crust, which were transported and deposted to form the protolith of the Cretaceous mica schists. Age pattern comparisons indicate that the age populations of the Cretaceous mica schists are significantly distinct from those of other Cretaceous strata in the Himalaya. It is obvious that the protolith of the Cretaceous mica schists were formed in an independent terrane (Arun) in the Neo‐Tethys with significant tectonic separations proventing any inputs from the Tibetan Himalaya, Greater Himalaya, or Indian Craton since 120 Ma. Combined with published U–Pb ages and other geological data, our data supports the archipelago palaeogeography with rifted terranes in the Neo‐Tethys Ocean, shedding light on the multiple amalgamation events along the India‐Asia collision zone.
Two mineralization events in the Laozuoshan Au deposit, north‐east China: Evidence from Re–Os geochronology and trace element geochemistry
Authors: Shi Kaituo , Wang Keyong , Ulrich Thomas , Ma Xueli , Sun Qingfei , Wang Rui
Published: November 2020

The Laozuoshan deposit, located in the central Jiamusi Block of north‐east China, is characterized by two types of mineralization, including principal skarn‐type Au mineralization occurring along the contact zone between granite and migmatite, and minor auriferous quartz‐arsenopyrite veins hosting in plagiogranite and granite. Re–Os dating of auriferous pyrrhotite and arsenopyrite were performed to determine the metallogenic ages of the Laozuoshan gold deposit. Analyses of arsenopyrite from quartz vein‐type ores yield a weighted average model age of 89.0 ± 3.1 Ma (mean standard weighted deviation（MSWD） = 9.3), which is within uncertainty in agreement with the 187Re/188Os versus 187Os/188Os isochron age of 93.2 ± 2.6 Ma (MSWD = 1.3) and the 187Re versus 187Os isochron age of 97 ± 14 Ma (MSWD = 7.4). Pyrrhotite samples from skarn‐type ores have model ages from 82.6 Ma to 424.8 Ma, indicating an unclosed Re–Os isotope system. However, the skarn‐type Au mineralization likely occurred during the Permian following the emplacement of the Laozuoshan granite. Results of laser ablation inductively coupled plasma mass spectrometry (LA‐ICP‐MS) trace element analysis show that element contents in sulphides from different types of ores are systematically different. Au, Ag, Bi, Pb, Co, and Ni are significantly enriched in skarn‐type arsenopyrite. These data suggest that the Laozuoshan deposit formed from two gold mineralization events. Combined with previous studies, we suggest that the skarn‐type Au mineralization was associated with the subduction of the Panthalassic oceanic plate, whereas the rollback of the Palaeo‐Pacific Plate was responsible for the quartz vein‐type Au mineralization in the Laozuoshan deposit. The multiple mineralization events have important implications for regional exploration.
Increased Use of Bayesian Network Models Has Improved Environmental Risk Assessments
Authors: Moe S Jannicke , Carriger John F , Glendell Miriam
Published: November 2020

Environmental and ecological risk assessments are defined as the process for evaluating the likelihood that the environment may be impacted as a result of exposure to stressors. Although this definition implies the calculation of probabilities, risk assessments traditionally rely on nonprobabilistic methods such as calculation of a risk quotient. Bayesian network (BN) models are a tool for probabilistic and causal modeling, increasingly used in many fields of environmental science. Bayesian networks are defined as directed acyclic graphs where the causal relationships and the associated uncertainty are quantified in conditional probability tables. Bayesian networks inherently incorporate uncertainty and can integrate a variety of information types, including expert elicitation. During the last 2 decades, there has been a steady increase in reports on BN applications in environmental risk assessment and management. At recent annual meetings of the Society of Environmental Toxicology and Chemistry (SETAC) North America and SETAC Europe, a number of applications of BN models were presented along with new theoretical developments. Likewise, recent meetings of the European Geosciences Union (EGU) have dedicated sessions to Bayesian modeling in relation to water quality. This special series contains 10 articles based on presentations in these sessions, reflecting a range of BN applications to systems, ranging from cells and populations to watersheds and national scale. The articles report on recent progress in many topics, including climate and management scenarios, ecological and socioeconomic endpoints, machine learning, diagnostic inference, and model evaluation. They demonstrate that BNs can be adapted to established conceptual frameworks used to support environmental risk assessments, such as adverse outcome pathways and the relative risk model. The contributions from EGU demonstrate recent advancements in areas such as spatial (geographic information system [GIS]–based) and temporal (dynamic) BN modeling. In conclusion, this special series supports the prediction that increased use of Bayesian network models will improve environmental risk assessments. Integr Environ Assess Manag 2021;17:53–61. © 2020 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC)
Five immune‐gene‐signatures participate in the development and pathogenesis of Kawasaki disease
Authors: Nie Han , Wang Shizhi , Wu Quanli , Xue Danni , Zhou Weimin
Published: November 2020

Objective

To screen for immune genes that play a major role in Kawasaki disease and to investigate the pathogenesis of Kawasaki disease through bioinformatics analysis.

Methods

Kawasaki disease‐related datasets GSE18606, GSE68004, and GSE73461 were downloaded from the Gene Expression Omnibus database. Three microarrays were integrated and standardized to include 173 Kawasaki disease samples and 101 normal samples. The samples were analyzed using CIBERSORT to obtain the infiltration of 22 immune cells and analyze the differential immune cells in the samples and correlations. The distribution of the samples was analyzed using principal component analysis (PCA). Immune‐related genes were downloaded, extracted from the screened samples and analyzed for differential analysis (different expression genes [DEG]) and weighted gene co‐expression network analysis (WGCNA). We constructed coexpression networks, and used the cytohobbe tool in Cytoscape to analyze the coexpression networks and select the immune genes that played a key role in them.

Results

Immune cell infiltration analysis showed that B cells naive, T cells CD8, natural killer (NK) cells activated, and so forth were highly expressed in normal samples. T cells CD4 memory activated, monocytes, neutrophils, and so forth were highly expressed in Kawasaki disease samples. PCA results showed a significant difference in the distribution of normal and Kawasaki disease samples. From the screened samples, 97 upregulated and 103 downregulated immune‐related genes were extracted. WGCNA analysis of DEG yielded 10 gene modules, of which the three most relevant to Kawasaki disease were red, yellow, and gray modules. They were associated with cytokine regulation, T‐cell activation, presentation of T‐cell receptor signaling pathways, and NK cell‐mediated cytotoxicity. CXCL8, CCL5, CCR7, CXCR3, and CCR1 were identified as key genes by constructing a coexpression network.

Conclusion

Our study shows that we can distinguish normal samples from Kawasaki disease samples based on the infiltration of immune cells, and that CXCL8, CCL5, CCR7, CXCR3, and CCR1 may play important roles in the development of Kawasaki disease.
Influence of Prednisolone and Alendronate on the de novo Mineralization of Zebrafish Caudal Fin
Authors: Bohns Fabio Rocha , Shih Yann‐Rong , Chuang Yung‐Jen , Akhtar Riaz , Chen Po‐Yu
Published: November 2020

Dysregulated balance between bone resorption and formation mediates the onset and progression of osteoporosis. The administration of prednisolone is known to induce osteoporosis, whereas alendronate is commonly used to reverse the process. However, the assessment of the effects of such medicines on the nanostructure of bone remodeling and mechanical properties remains a major technical challenge. The aim of this study was to apply various analytical approaches to evaluate the compositional, morphological, and mechanical properties of regenerative zebrafish caudal fin bony rays affected by prednisolone and alendronate. Adult wild‐type AB strain zebrafish were first exposed to 125μM of prednisolone for 14 days to develop glucocorticoid‐induced osteoporosis. Fish fins were then amputated and let to regenerate for 21 days in tank water containing 30μM of alendronate or no alendronate. The lepidotrichia in the proximal and distal regions were evaluated separately using confocal microscope, scanning electron microscope, electron‐dispersive spectroscopy, Raman spectroscopy, atomic force microscopy, and a triboindenter. As expected, prednisolone led to significant osteoporotic phenotypes. A decrease of Ca/P ratio was observed in the osteoporotic subjects (1.46 ± 0.04) as compared to the controls (1.74 ± 0.10). Subsequent treatment of alendronate overmineralized the bony rays during regeneration. Enhanced phosphate deposition was detected in the proximal part with alendronate treatment. Moreover, prednisolone attenuated the reduced elastic modulus and hardness levels (5.60 ± 5.04 GPa and 0.12 ± 0.17 GPa, respectively), whereas alendronate recovered them to the pre‐amputation condition (8.68 ± 8.74 GPa and 0.34 ± 0.47 GPa, respectively). As an emerging model of osteoporosis, regrowth of zebrafish caudal fin was shown to be a reliable assay system to investigate the various effects of medicines in the de novo mineralization process. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Informing Development of Bispecific Antibodies Using Physiologically Based Pharmacokinetic‐Pharmacodynamic Models: Current Capabilities and Future Opportunities
Authors: Gibbs John P. , Yuraszeck Theresa , Biesdorf Carla , Xu Yang , Kasichayanula Sreeneeranj
Published: November 2020

Antibody therapeutics continue to represent a significant portion of the biotherapeutic pipeline, with growing promise for bispecific antibodies (BsAbs). BsAbs can target 2 different antigens at the same time, such as simultaneously binding tumor‐cell receptors and recruiting cytotoxic immune cells. This simultaneous engagement of 2 targets can be potentially advantageous, as it may overcome disadvantages posed by a monotherapy approach, like the development of resistance to treatment. Combination therapy approaches that modulate 2 targets simultaneously offer similar advantages, but BsAbs are more efficient to develop. Unlike combination approaches, BsAbs can facilitate spatial proximity of targets that may be necessary to induce the desired effect. Successful development of BsAbs requires understanding antibody formatting and optimizing activity for both targets prior to clinical trials. To realize maximal efficacy, special attention is required to fully define pharmacokinetic (PK)/pharmacodynamic (PD) relationships enabling selection of dose and regimen. The application of physiologically based pharmacokinetics (PBPK) has been evolving to inform the development of novel treatment modalities such as bispecifics owing to the increase in our understanding of pharmacology, utility of multiscale models, and emerging clinical data. In this review, we discuss components of PBPK models to describe the PK characteristics of BsAbs and expand the discussion to integration of PBPK and PD models to inform development of BsAbs. A framework that can be adopted to build PBPK‐PD models to inform the development of BsAbs is also proposed. We conclude with examples that highlight the application of PBPK‐PD and share perspectives on future opportunities for this emerging quantitative tool.
Point‐of‐care lung ultrasound findings in the pediatric emergency clinic during the COVID‐19 pandemic
Authors: Türe Esra , Korkmaz Muhammet Furkan , Aksoy Fatma Dilşad , Ceylan Demirbaş Başak , Menekşe Burcu , Çiftçi Mehtap , Korkmaz Merve
Published: November 2020

Purpose

To describe our experience concerning lung ultrasound (LUS) in the pediatric emergency clinic, and to investigate the diagnostic value of LUS in coronavirus disease‐2019 (COVID‐19).

Methods

Patients aged under 18 admitted to the pediatric emergency clinic with suspicion of COVID‐19, who underwent point‐of‐care LUS and from whom COVID‐19 reverse transcription polymerase chain reaction (RT‐PCR) samples were collected, were included in the study.

Results

Point‐of‐care LUS was performed on 74 patients in the emergency room. LUS findings were more sensitive than chest X‐ray in the early stages of the disease and in mild cases. Involvement was observed at LUS despite RT‐PCR being negative in some symptomatic patients with a COVID‐19 contact history.

Conclusions

We think that LUS can be beneficial in terms of identifying patients with lung involvement and staging their severity in this new disease in pediatric emergency clinics. The procedure is noninvasive, rapid, reproducible, and low cost, involving simple sterilization. Based on the current literature and our own practical experience, we think that increased use of point‐of‐care LUS can protect patients from unnecessary radiation and treatment delays during the COVID‐19 pandemic.
Surface translocator protein 18 kDa (TSPO) localization on immune cells upon stimulation with LPS and in ART-treated HIV+ subjects
Authors: Blevins Lance K , Crawford Robert B , Azzam Diana J , Guilarte Tomás R , Kaminski Norbert E
Published: November 2020

Translocator protein 18 kDa (TSPO) is a well-known outer mitochondrial membrane protein and it is widely used as a biomarker of neuroinflammation and brain injury. Although it is thought that TSPO plays key roles in a multitude of host cell functions, including steroid biosynthesis, apoptosis, generation of reactive oxygen species, and proliferation, some of these functions have recently been questioned. Here, we report the unexpected finding that circulating immune cells differentially express basal levels of TSPO on their cell surface, with a high percentage of monocytes and neutrophils expressing cell surface TSPO. In vitro stimulation of monocytes with LPS significantly increases the frequency of cells with surface TSPO expression in the absence of altered gene expression. Importantly, the LPS increase in TSPO cell surface expression in monocytes appears to be selective for LPS because two other distinct monocyte activators failed to increase the frequency of cells with surface TSPO. Finally, when we quantified immune cell TSPO surface expression in antiretroviral therapy-treated HIV+ donors, a chronic inflammatory disease, we found significant increases in the frequency of TSPO surface localization, which could be pharmacologically suppressed with ∆9-tetrahydrocannabinol. These findings suggest that cell surface TSPO in circulating leukocytes could serve as a peripheral blood-based biomarker of inflammation.
Synthetic MRI: Technologies and Applications in Neuroradiology
Authors: Ji Sooyeon , Yang Dongjin , Lee Jongho , Choi Seung Hong , Kim Hyeonjin , Kang Koung Mi
Published: November 2020

Synthetic MRI is a technique that synthesizes contrast‐weighted images from multicontrast MRI data. There have been advances in synthetic MRI since the technique was introduced. Although a number of synthetic MRI methods have been developed for quantifying one or more relaxometric parameters and for generating multiple contrast‐weighted images, this review focuses on several methods that quantify all three relaxometric parameters (T1, T2, and proton density) and produce multiple contrast‐weighted images. Acquisition, quantification, and image synthesis techniques are discussed for each method. We discuss the image quality and diagnostic accuracy of synthetic MRI methods and their clinical applications in neuroradiology. Based on this analysis, we highlight areas that need to be addressed for synthetic MRI to be widely implemented in the clinic.

Level of Evidence

5

Technical Efficacy Stage

1
Future changes in precipitation for identified sub‐regions in East Asia using bias‐corrected multi‐RCMs
Authors: Park Changyong , Lee Gil , Kim Gayoung , Cha Dong‐Hyun
Published: November 2020

Water management is a crucial issue in East Asia and is significantly influenced by climate change. Because East Asia's precipitation characteristics are varied and complex, it is necessary to implement the analysis of the future changes in precipitation on an objectively classified, specific sub‐regional level to effectively solve these problems. In this study, sub‐regions were objectively classified according to their precipitation characteristics, based on the present observations in East Asia. Additionally, the bias‐correction technique was applied to the regional climate model (RCM) to yield more reliable future precipitation predictions for the sub‐regions. We obtained the following four key results in this study. (1) The classified sub‐regions corresponded well to the observed annual precipitation distribution and adequately reflected the influence of the summer monsoon. The annual precipitation of the classified sub‐regions exhibited a decreasing trend in arid regions and an increasing trend in humid areas. (2) Because the bias‐corrected RCM was able to simulate annual precipitation reasonably, this technique was applied to future scenarios to analyse future changes in precipitation for each classified sub‐region. (3) Future annual precipitation will increase significantly in the region spanning from the western part of Southern China to the area around the Bohai Sea, while the temporal variations of the climatological daily precipitation indicated that sub‐regions under the influence of the East Asian summer monsoon (EASM) will be predicted an increase in second peaks during the summer. Hence, in the future, the EASM rain belt will be strengthened and its average location will move northward from its present location. (4) Because the high‐intensity extreme precipitation indices are expected to have a more considerable increase in all the classified sub‐regions, there is a need to solidify response measures against disasters that could arise from these changes in the East Asian region.
The effect of the inclusion of pea in lamb fattening concentrate on in vitro and in situ rumen fermentation
Authors: Joy Margalida , Rufino‐Moya Pablo , Lobón Sandra , Blanco Mireia
Published: November 2020

BACKGROUND

The objective of this study was to evaluate the effect of the proportion of pea (0%, 10%, 20%, and 30%), as a partial replacement for soybean meal (SBM) in the fattening concentrate, on ruminal fermentation in lambs. Gas and methane (CH4) production, in vitro dry matter degradability (IVDMD), ammonia (NH3‐N), and volatile fatty acid (VFA) production after 24 h of incubation were evaluated. The concentrates were also incubated in the rumen of the wethers for 2, 4, 6, 8, 12, and 24 h to evaluate the effects of pea inclusion on in situ dry matter degradability (DMD), organic matter degradability (OMD), nitrogen degradability (ND), NH3‐N, and VFA production.

RESULTS

In the in vitro assay, the inclusion of pea only affected gas production (mL day−1 degraded dry matter), CH4 production (mL day−1 degraded dry matter), and IVDMD (P < 0.05), and tended to affect NH3‐N content (P < 0.10) without affecting VFA production. In the in situ assay, the inclusion of pea increased DMD, OMD, and ND linearly (P < 0.001), whereas pea inclusion decreased NH3‐N content linearly (P < 0.05). Neither total VFA production nor the proportion of acetic acid were affected by pea inclusion (P > 0.05), but the propionic proportion increased with the proportion of pea included.

CONCLUSIONS

The best level of pea inclusion in the concentrate could not be established based on the results of this study. However, the results showed that the inclusion of pea provides a good alternative protein source. © 2020 Society of Chemical Industry
Coastal hypoxia and eutrophication as key controls on benthic release and water column dynamics of iron and manganese
Authors: Lenstra Wytze K. , Hermans Martijn , Séguret Marie J.M. , Witbaard Rob , Severmann Silke , Behrends Thilo , Slomp Caroline P.
Published: November 2020

Continental shelves are a major source of iron (Fe) and manganese (Mn) to marine waters. Here, we investigate controls on benthic release of Fe and Mn and the impact on the water column in the Baltic Sea. We find high in situ benthic release rates of dissolved Fe and Mn at seasonally hypoxic sites (bottom water oxygen between 0–63 μmol L−1) receiving high inputs of organic matter. We find that benthic Fe and Mn release is sensitive to bottom water oxygen concentrations. Benthic Fe release is likely additionally controlled by Fe–sulfur redox chemistry in the surface sediment. For Mn, benthic release correlates positively with Mn oxide availability in the surface sediment. Benthic release contributes to high dissolved Fe and Mn concentrations in the water column and is amplified by repeated cycling of Fe and Mn between the sediment and overlying water through benthic release, oxidation in the water column, deposition as metal oxides, followed by reductive dissolution. Most water column Fe (∼ 80%) is present in particulate form near the seafloor. In contrast to Fe, a large percentage of the Mn remains dissolved (∼ 50%). We show that easily reducible Fe and Mn oxides are key forms of particulate Fe and Mn in suspended matter. The Baltic Sea represents a highly eutrophic, low oxygen end‐member when compared to other modern coastal systems. Our results imply that, upon continued eutrophication and deoxygenation of the coastal ocean, benthic release of dissolved Fe and Mn from continental shelves could become greater than previously thought.
Whole‐exome sequencing identified novel compound heterozygous variants in a Chinese neonate with liver failure and review of literature
Authors: Qin Zailong , Yang Qi , Yi Shang , Huang Limei , Shen Yiping , Luo Jingsi
Published: November 2020

Background

Liver failure caused by TRMU is a rare hereditary disorder and clinically manifests into metabolic acidosis, hyperlactatemia, and hypoglycemia. Limited spectrum of TRMU pathogenic variants has been reported.

Methods

Whole‐exome sequencing was employed for the diagnosis of a 5‐day‐old female who suffered from severe neonatal hyperlactatemia and hypoglycemia since birth. Sanger sequencing was performed to confirm the origin of the variants subsequently. Variants classification was followed to ACMG guideline.

Results

A compound heterozygosity of a frameshiftc.34_35dupTC (p.Gly13fs) and a missense c.244T>G (p.Phe82Val) in TRMU was detected, both variants are novel and pathogenic. Analysis of clinical and genetic information including patients reported previously indicated that there is no significant correlation between the genotype and the phenotype of TRMU‐caused liver failure.

Conclusion

To the best of our knowledge, this is the first case report of TRMU‐caused liver failure in China. Whole‐exome sequencing is effective for conclusive diagnosis of this disorder and beneficial for its clinical management.
Missense mutations in EDA and EDAR genes cause dominant syndromic tooth agenesis
Authors: Andreoni Francesca , Sgattoni Claudia , Bencardino Daniela , Simonetti Oriana , Forabosco Antonino , Magnani Mauro
Published: November 2020

Background

Hypohidrotic ectodermal dysplasia (HED) is the most common form of ectodermal dysplasia and is mainly associated with mutations in the EDA, EDAR, and EDARADD responsible for the development of ectodermal‐derived structures. HED displays different modes of inheritance according to the gene that is involved, with X‐linked EDA‐related HED being the most frequent form of the disease.

Methods

Two families with tooth agenesis and manifestations of HED underwent clinical examination and EDA, EDAR, and EDARADD genetic analysis. The impact of the novel variant on the protein was evaluated through bioinformatics tools, whereas molecular modeling was used to predict the effect on the protein structure.

Results

A novel missense variant was identified in the EDAR (c.287T>C, p.Phe96Ser) of a female child proband and her mother, accounting for autosomal dominant HED. The genetic variant c.866G>A (p.Arg289His) in EDA, which has been previously described, was observed in the male proband of another family confirming its role in X‐linked HED. The inheritance model of the missense mutation showed a different relationship with X‐linked HED and non‐syndromic tooth agenesis.

Conclusion

Our findings provide evidence of variable expression of HED in heterozygous females, which should be considered for genetic counseling, and different modes of inheritance related to tooth development.
Walking activity in a large cohort of boys with Duchenne muscular dystrophy
Authors: Lott Donovan J. , Taivassalo Tanja , Senesac Claudia R. , Willcocks Rebecca J. , Harrington Ann M. , Zilke Kirsten , Cunkle Hilary , Powers Catherine , Finanger Erika L. , Rooney William D. , Tennekoon Gihan I. , Vandenborne Krista
Published: November 2020

Introduction

In this study we explored walking activity in a large cohort of boys with Duchenne muscular dystrophy (DMD).

Methods

Step activity (monitored for 7 days), functional ability, and strength were quantified in ambulatory boys (5‐12.9 years of age) with DMD and unaffected boys. Ambulatory status was determined 2 years later.

Results

Two to 5 days of activity monitoring predicted weekly step activity (adjusted R2 = 0.80‐0.95). Age comparisons revealed significant declines for step activity with increasing age, and relationships were found between step activity with both function and strength (P < .01). Our regression model predicted 36.5% of the variance in step activity. Those who were still ambulatory after 2 years demonstrated baseline step activity nearly double that of those who were no longer walking 2 years later (P < .01).

Discussion

Step activity for DMD is related to and predictive of functional declines, which may be useful for clinical trials.
Degrees earned by faculty teaching in soil science preparatory programs at universities in the USA
Authors: Brevik Eric C. , Vaughan Karen
Published: November 2020

In the early 2000s some were concerned that few soil science graduate students were receiving their bachelor's degrees in soil science. However, no studies were conducted to investigate this or how it may have changed over time. Information available on university webpages for faculty in the United States was used to determine the faculty's bachelor's, master's, and doctoral degree disciplines. Faculty rank was used to determine if a change had occurred in the percentage of faculty who received their bachelor's degrees in soil science over time. Only 16% of faculty teaching in programs that prepare graduates to work as soil scientists received their bachelor's degrees in soil science. This percentage increased to 56 and 67% who received their master's and doctoral degrees, respectively, in soil science, but about 26% of faculty who teach in soil science preparatory programs did not have any degrees that could be identified as a “soil science” degree. The degrees that faculty received their training in also differed by their current soil science specialty area. About 13% of assistant professors and 20% of full professors received their bachelor's degrees in soil science, so the percentage of students entering soil science graduate programs with a bachelor's degree in soil science appears to have declined with time. However, a majority of soil science graduate students having bachelor's degrees from other fields also appears to have been common going back at least several decades.
Linking student self‐regulated learning profiles to achievement and engagement in mathematics
Authors: Cleary Timothy J. , Slemp Jacqueline , Pawlo Erica R.
Published: November 2020

The current study identified self‐regulated learning (SRL) profiles of middle school students and examined differences among these profiles across classroom engagement and mathematics achievement outcomes. Using student motivational, regulatory, and contextual variables, cluster analysis revealed a four‐factor solution as most interpretable. The four clusters varied across two dimensions (i.e., SRL and perceived contextual supports) and levels (i.e., high and low). Students who reported strong SRL skills displayed the most adaptive outcomes, in terms of both classroom engagement and mathematics achievement. The least adaptive profile included students who reported poor SRL skills and who exhibited a weak connection to school and perceived support from teachers. This latter cluster displayed statistically significant lower standardized mathematics achievement scores than all other clusters. Implications and directions for future research are emphasized.