bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of SMS Reminders on Adherence in a Self-Guided Internet-Delivered Intervention for Adults With ADHD
Authors: Nordby Emilie S. , Gjestad Rolf , Kenter Robin M. F. , Guribye Frode , Mukhiya Suresh K. , Lundervold Astri J. , Nordgreen Tine
Published: May 2022

Background

Self-guided Internet-delivered interventions may serve as an accessible and flexible non-pharmacological treatment supplement for adults with ADHD. However, these interventions are challenged by low adherence.

Objective

To examine whether weekly SMS reminders improve adherence to a self-guided Internet-delivered intervention for adults with ADHD.

Method

The study used a multiple randomized trial design where the participants who had not completed their weekly module within 2 days were randomized to either receive or not receive an SMS reminder. The primary outcome was adherence, defined as module completion, logins, time spent on intervention, and self-reported practice of coping strategies.

Results

A total of 109 adults with a self-reported ADHD diagnosis were included in the study. The results showed that SMS reminders were associated with an increased likelihood of login within 48 h during the second module of the intervention, but not for the remaining modules. Moreover, receiving an SMS reminder was associated spending more time on the modules and faster login time in module three and five, specifically. However, the overall results did not show an effect of SMS reminders on module completion, number of logins or practice of coping strategies.

Conclusion

The results showed that SMS reminders do not improve number of logins, module completion rates or practice of coping strategies, but they may lead to faster login time and more time spent on the modules. To utilize the potential of self-guided Internet-delivered intervention in making non-pharmacological accessible for adults with ADHD, new methods to facilitate meaningful engagement should be developed and tested.

Trial Registration

ClinicalTrials.gov NCT04511169.
Description of Starch Granules From Edible Acorns (Oak), Palms, and Cycads in Southern China
Authors: Li Zhao , Barton Huw , Wang Weiwei , Yang Xiaoyan
Published: May 2022

A review of ethnological and archaeobotanical evidence shows the potential for a range of starch-rich woody plants, beyond tuberous plants, to have been important foods in prehistoric south subtropical China. In this paper we review the size and shape characteristics of starch granules non-tuberous woody plants (Palms, Cycads and Acorns) that our research has identified as important sources of carbohydrates for prehistoric communities. The study sample consists of 34 modern starch reference samples across eight genera (Palms:Arenga, Caryota,; Cycads:Cycas; and, Acorns:Castanopsis,Fagus, Lithocarpus, Quercus,andQuercussectionCyclobalanopsis). Our descriptive criteria are developed granule descriptors standard in the literature and then assessed for their utility using multiple correspondence analysis. The results demonstrate that both morphometric characteristics and the maximum size of granules are valuable for distinguishing starch granules at various taxonomic levels. Of the five morphometric characteristics recorded in this study sample, granule shape is the most effective variable for granule identification.
Geometry and Kinematics Characteristics of Strike-Slip Fault Zone in Complex Structure Area: A Case Study From the South No. 15 Strike-Slip Fault Zone in the Eastern Sichuan Basin, China
Authors: Cheng Xiaoyun , Ding Wenlong , Pan Lei , Zou Yutao , Li Yuntao , Yin Yixing , Ding Shihao
Published: May 2022

The eastern Sichuan Basin has undergone multiple stages of tectonic evolution and shows complex structural characteristics. It is found that there are a series of NW-SE base-trending strike-slip faults in this area besides NE-SW strike-blocking structures. There are almost no previous studies on strike-slip faults in the eastern Sichuan Basin. This paper fills in the blank of geometry and kinematics research on the strike-slip fault zone in this area. Based on highly precise 3D seismic section, coherent attribute slice and time slice, the geometric and kinematic characteristics of the fault are analyzed. The dynamic characteristics are analysed based on the structural style of the superimposed development model and the nature and activity intensity of strike-slip faults in different periods. and it was found that No. 15 strike-slip fault was a large basement strike-slip fault. The research results show that the profile of the No. 15 strike-slip fault mainly shows a subvertical fracture, positive flower structure and negative flower structure and a composite flower structure with positive and negative flower structures superimposed on each other in the upper and lower planar sections with linearly outspread and zonal distribution characteristics; spatially, there is a “ribbon” effect and a “dolphin” effect. the left strike-slip distance of the TS interface is 0.462 km, and the right strike-slip distance of the TP2 interface is 0.782 km. The strike-slip fault experienced at least three active stages of superimposed deformation during its formation and reconstruction, among which episode II in the middle Caledonian movement was the main active stage of the No. 15 strike-slip fault zone. This study of the structural style and genetic mechanism of a strike-slip fault zone is of guiding significance to the exploration and development of strike-slip fault-controlled reservoirs in the study area.
Measuring Inclusive Education in Portuguese Schools: Adaptation and Validation of a Questionnaire
Authors: Carvalho Marisa , Cruz Joana , Azevedo Helena , Fonseca Helena
Published: May 2022

The debate about inclusive education has gained considerable attention in policy, research, and practice in the last decades. Therefore, there is also a growing interest in assessing how inclusive education occurs in schools. Self-assessment and self-reflection tools are strategic to examine schools’ inclusion and guide needed changes. This study attempts to provide Portuguese schools with self-assessment tools for improvement. Themis Inclusion Tool was translated and adapted into a Portuguese version named Resources and Practices for Inclusive Education and evaluated the instrument’s psychometric structure. A web survey was completed online by 924 participants. An EFA suggested two different factors: Inclusive Resources, human, technical and technological resources used to promote learning and; Inclusive Practices, beliefs and behaviors that can be implemented to promote learning. These two factors were supported by confirmatory analysis. Overall, the Resources and Practices for Inclusive Education presented a robust factorial structure and good psychometric properties, appearing to be a valid and reliable measure for assessing inclusive education in Portuguese schools.
The Effect of Inactivated SARS-CoV-2 Vaccines on TRAB in Graves’ Disease
Authors: Huang LingHong , Jiang ZhengRong , Zhou JingXiong , Chen YuPing , Huang HuiBin
Published: May 2022

Background

The ongoing coronavirus disease 2019 (COVID-19) pandemic has forced the development of vaccines. Reports have suggested that vaccines play a role in inducing autoimmune diseases (AIDs). Scattered cases have reported that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines may promote thyroid disease, including Graves’ disease (GD). However, the effect of inactivated SARS-CoV-2 vaccine on GD remains unclear. The aim of the present study was to investigate the response of thyrotropin receptor antibody (TRAB) to inactivated SARS-COV-2 vaccines.

Methods

We conducted a retrospective study to observe the differences in thyroid function and TRAB trends between pre-vaccination (n=412) and post-vaccination (n=231) groups at an interval of 2 months. We then retrospectively observed the differences in serum thyroid function and TRAB levels at 3 months before (n=280), 1 month before (n=294), 1 month after (n=306), and 3 months after (n=250) vaccination. Subsequently, 173 GD patients who were not vaccinated with inactivated SARS-COV-2 vaccines were selected for a prospective study. Thyroid function and TRAB assessment were performed before 3 and 1 months and 1 and 3 months after the first dose of vaccination and were then compared by repeated measures ANOVA to explore their dynamic changes.

Results

A retrospective study preliminarily observed that the trend of TRAB post-vaccination was opposite of that pre-vaccination (p=0.000), serum TRAB levels decreased before vaccination and increased after vaccination. In this prospective study, repeated measures ANOVA indicated significant differences in serum FT3 (p=0.000), FT4 (p=0.000), TSH (p=0.000), and TRAB (p=0.000) levels at different time points before and after vaccination. Serum TRAB levels showed dynamic changes that decreased significantly at 1 month before vaccination (p=0.000), no significant differences at 1 month after vaccination (p=0.583), and reflected an upward trend at 3 months after vaccination (p=0.034). Serum FT3 and FT4 levels showed similar trends to serum TRAB levels before and after vaccination. Instead, the serum TSH levels showed a continuous upward trend over time.

Conclusion

Based on the results obtained in both retrospective and prospective studies, we concluded that serum TRAB levels decreased less after inactivated SARS-CoV-2 vaccination and showed an upward trend, which may be related to humoral immunity induced by vaccination.
The Saturation Effect of Obesity on Bone Mineral Density for Older People: The NHANES 2017–2020
Authors: Zhang Ya , Pu Jian
Published: May 2022

Introduction

Previous studies have shown that obesity has a positive effect on bone mineral density (BMD). However, excessive obesity is harmful to health, especially in older adults. In addition, it is unclear what body mass index (BMI) and waist circumference (WC) to maintain for the most beneficial BMD in older adults.

Methods

Multivariate logistic regression models were used to investigate the association between BMI, WC, and femoral neck BMD using the most recent data from the 2017–2020 National Health and Nutrition Examination Survey (NHANES). Fitting smoothing curves and saturation effects analysis were also used to determine the association of nonlinear relationships between BMI, WC, and femoral neck BMD.

Results

The analysis included a total of 2,903 adults. We discovered that BMD and WC were positively linked to femoral neck BMD. The favorable associations of BMI and WC with femoral neck BMD were maintained in all subgroup analyses stratified by sex and race, except among Mexican Americans. Furthermore, smoothing curve fitting revealed that the link between BMI and BMD was not only a linear connection, and that there was a saturation point. The BMI saturation value in the femoral neck BMD was 24.3 (kg/m2), according to the saturation effect analysis.

Conclusions

In persons over the age of 50, our research found a positive relationship between obesity and BMD, and we also found a saturation value between BMI and BMD. According to this study, maintaining BMI at a moderate level (about 24.3 kg/m2) would result in an optimal balance between BMI and BMD in adults over 50 years of age.
Evolving Roles of Natural Terpenoids From Traditional Chinese Medicine in the Treatment of Osteoporosis
Authors: Zhuo Yue , Li Meng , Jiang Qiyao , Ke Hanzhong , Liang Qingchun , Zeng Ling-Feng , Fang Jiansong
Published: May 2022

Osteoporosis (OP) is a systemic metabolic skeletal disease which can lead to reduction in bone mass and increased risk of bone fracture due to the microstructural degradation. Traditional Chinese medicine (TCM) has been applied in the prevention and treatment of osteoporosis for a long time. Terpenoids, a class of natural products that are rich in TCM, have been widely studied for their therapeutic efficacy on bone resorption, osteogenesis, and concomitant inflammation. Terpenoids can be classified in four categories by structures, monoterpenoids, sesquiterpenoids, diterpenoids, and triterpenoids. In this review, we comprehensively summarize all the currently known TCM-derived terpenoids in the treatment of OP. In addition, we discuss the possible mechanistic-of-actions of all four category terpenoids in anti-OP and assess their therapeutic potential for OP treatment.
Inorganic Phosphorus Transformation and Phosphorus Adsorption–Desorption Properties of Soil in a Cotton Field Under Mulched Drip Irrigation in Xinjiang: A Four-Year Field Assessment
Authors: Tang Xuexia , Liu Meijuan , Sheng Jiandong , Chai Zhongping , Feng Gu , Chen Bolang
Published: May 2022

Phosphorus (P) fertilizer is generally applied to enhance the soil P pool and meet crop demand, but most of the added P is absorbed by soil. This study aimed to explore the importance of P fractions and adsorption–desorption characteristics on the demand for P fertilizer to determine the optimum P fertilizer amount for a cotton field under mulched drip irrigation in Xinjiang, China. A 4-year experiment (2016–2019) was conducted in a cotton field to evaluate the effects of five P fertilizer addition levels (0, 75, 150, 300, and 450 kg P2O5 ha−1 year−1) on inorganic P fractions and P adsorption–desorption properties at different soil depths and explore the effects of soil properties on P adsorption. The 4-year continuous P fertilization enhanced the inorganic P content and altered the proportions of various P forms. A large proportion of P accumulated in soil was transformed into Ca8-P, followed by Ca2-P, mainly in the surface layer. The accumulation and transformation of P in fertilized soil reduced P adsorption and enhanced P desorption. Soils with higher P application levels had higher inorganic P accumulation with lower adsorption and higher desorption. The total P and Olsen-P in a 0- to 5-cm soil layer; Ca8-P and calcium carbonate (CaCO3) in a 5- to 10-cm soil layer; Olsen-P, Ca10-P, clay, and cation exchange capacity in a 10- to 20-cm soil layer; and Olsen-P in a 20- to 40-cm soil layer significantly affected the P adsorption–desorption (p < 0.05). The application rate of 75–150 kg P2O5 ha−1 year−1 produced lower inorganic P accumulation, favorable adsorption–desorption properties, and high cotton yield, and thus could be considered the optimal P fertilizer application level.
Comparing Convolutional Neural Network and Machine Learning Models in Landslide Susceptibility Mapping: A Case Study in Wenchuan County
Authors: Zhang Sikui , Bai Lin , Li Yuanwei , Li Weile , Xie Mingli
Published: May 2022

Landslides are one of the most widespread disasters and threaten people’s lives and properties in many areas worldwide. Landslide susceptibility mapping (LSM) plays a crucial role in the evaluation and extenuation of risk. To date, a large number of machine learning approaches have been applied to LSM. Of late, a high-level convolutional neural network (CNN) has been applied with the intention of raising the forecast precision of LSM. The primary contribution of the research was to present a model which was based on the CNN for LSM and methodically compare its capability with the traditional machine learning approaches, namely, support vector machine (SVM), logistic regression (LR), and random forest (RF). Subsequently, we used this model in the Wenchuan region, where a catastrophic earthquake happened on 12 May 2008 in China. There were 405 valuable landslides in the landslide inventory, which were divided into a training set (283 landslides) and validation set (122 landslides). Furthermore, 11 landslide causative factors were selected as the model’s input, and each model’s output was reclassified into five intervals according to the sensitivity. We also evaluated the model’s performance by the receiver operating characteristic (ROC) curve and several statistical metrics, such as precision, recall, F1-score, and other measures. The results indicated that the CNN-based methods achieved the best performance, with the success-rate curve (SRC) and prediction-rate curve (PRC) approaches reaching 93.14% and 91.81%, respectively. The current research indicated that the approach based on the CNN for LSM had both outstanding goodness-of-fit and excellent prediction capability. Generally, the LSM in our research is capable of advancing the ability to assess landslide susceptibility.
Role of Financial Development, Green Technology Innovation, and Macroeconomic Dynamics Toward Carbon Emissions in China: Analysis Based on Bootstrap ARDL Approach
Authors: Yang Jiayu , Sun Yunpeng , Sun Huaping , Lau Chi Keung Marco , Apergis Nicholas , Zhang Kun
Published: May 2022

This study focuses on determining the relationship between carbon emissions, financial development, population, green technology innovation, energy Consumption, and employment rate from 1980 to 2019 in China. The study applies the unit root test, bootstrapped ARDL cointegration, and the Granger causality to examine the data properties and association between the variables of interest. Empirical findings indicate that green technology innovations and financial development play a major role in environmental protection, specifically in the long run. In contrast, energy consumption and employment rate are more vulnerable to protecting the natural environment in China. On the other side, the findings under short-run estimation do not support the role of green technology innovation in reducing environmental degradation. Based on the empirical findings, it is suggested that a strong financial system would help to achieve long-run sustainability and the emissions mitigating effects can be further strengthen by implementing green technologies across industries. In doing so, strict environmental regulations can regulate the financial and traditional industrial sector in adoption of energy efficient technologies.
A Study on the Oil Price Cointegration Dynamic Process: Evidence From the Shanghai Crude Oil Futures
Authors: Wang Hongxia , Qiu Shushu , Yick Ho Yin , Dai Yuhu
Published: May 2022

This work studies the integration process of the Shanghai crude oil futures market in pricing discovery mechanism of global crude oil markets by conducting cointegration analysis and lead–lag causality tests. Using the representative samples of several futures contracts covering different listing periods, we conclude a significant and gradual change of the relations between the Shanghai crude oil futures market and international benchmarks, from unidirectional Granger causality to bidirectional Granger causality. The cointegration relationships become stable after about 2 years’ market development. Moreover, the Shanghai crude oil futures market always leads domestic (Daqing) crude oil spot market since 2019. Our evidences support that it has the increasing influence on domestic crude oil market and international benchmarks.
Changes in the Thermal and Hydrometeorological Forest Growth Climate During 1948–2017 in Northern Germany
Authors: Bat-Enerel Banzragch , Weigel Robert , Leuschner Christoph
Published: May 2022

Recent severe droughts and climate change projections have caused rising worries about the impacts of a warmer and drier climate on forests and the future of timber production. While recent trends in thermal and hydrometeorological climate factors have been studied in many regions on earth, less is known about long-term change in climate variables most relevant for tree health and productivity, i.e., temperature (T), precipitation (P), climatic water balance (CWB), and SPEI aridity index in early and mid-summer, when leaf unfolding and peak stem growth take place. Here, we analyze T, P, CWB, and SPEI trends separately for all growing season months (April-September) during the 1948–1982 (before the recent warming) and 1983–2017 periods (after the onset of warming) in their spatial variation across the North German Lowlands based on a dense climate station network. While trends in thermal and hydrometeorological variables were weak from 1948 to 1982, we find a significant decrease in April precipitation and increase in July precipitation from 1983 to 2017 throughout much of the study region, while June precipitation has decreased locally by 10 mm or more (or up to 20%). The cumulated growing-season CWB has deteriorated by up to 30 mm from 1948–1982 to 1983–2017 in most of the region except at the North Sea coast, where it became more favorable. Recent climate aridification is more pronounced in the drier South-east of the study region with a more continental climate, as indicated by stronger negative P, CWB, and SPEI trends for April, May, and June. We conclude that water availability especially in the physiologically important months April and June has deteriorated in the larger part of the North German Lowlands since the 1980s, increasingly impairing hydrometeorological forest growth conditions. The identified trends may serve as early-warning signals of anticipated future loss in tree vitality.
Tree Size Drives Diversity and Community Structure of Microbial Communities on the Bark of Beech (Fagus sylvatica)
Authors: Dreyling Lukas , Schmitt Imke , Dal Grande Francesco
Published: May 2022

Tree bark constitutes an ideal habitat for microbial communities, because it is a stable substrate, rich in micro-niches. Bacteria, fungi, and terrestrial microalgae together form microbial communities, which in turn support more bark-associated organisms, such as mosses, lichens, and invertebrates, thus contributing to forest biodiversity. We have a limited understanding of the diversity and biotic interactions of the bark-associated microbiome, as investigations have mainly focused on agriculturally relevant systems and on single taxonomic groups. Here we implemented a multi-kingdom metabarcoding approach to analyze diversity and community structure of the green algal, bacterial, and fungal components of the bark-associated microbial communities of beech, the most common broadleaved tree of Central European forests. We identified the most abundant taxa, hub taxa, and co-occurring taxa. We found that tree size (as a proxy for age) is an important driver of community assembly, suggesting that environmental filtering leads to less diverse fungal and algal communities over time. Conversely, forest management intensity had negligible effects on microbial communities on bark. Our study suggests the presence of undescribed, yet ecologically meaningful taxa, especially in the fungi, and highlights the importance of bark surfaces as a reservoir of microbial diversity. Our results constitute a first, essential step toward an integrated framework for understanding microbial community assembly processes on bark surfaces, an understudied habitat and neglected component of terrestrial biodiversity. Finally, we propose a cost-effective sampling strategy to study bark-associated microbial communities across large spatial or environmental scales.
Strategy of Nematophagous Fungi in Determining the Activity of Plant Parasitic Nematodes and Their Prospective Role in Sustainable Agriculture
Authors: Al-Ani Laith Khalil Tawfeeq , Soares Filippe Elias de Freitas , Sharma Ashutosh , de los Santos-Villalobos Sergio , Valdivia-Padilla Ana Victoria , Aguilar-Marcelino Liliana
Published: May 2022

In this review, we supply a framework for the importance of nematophagous fungi (nematophagous fungi [NF]) and their role in agricultural ecosystems. We characterize the taxonomy, diversity, ecology, and type of NF, depending on their interaction with plant-parasitic nematodes (PPNs). We described potential mechanisms of NF in the control of PPNs, the efficiency and methods of utilization, and the use of nematicides in sustainable agriculture. We explain the utilization of NF in nanotechnology as a new approach. NF are significant in the soil for having the effective potential for use in sustainable agriculture. These types of fungi belong to wide taxa groups, such as Ascomycota, Basidiomycota, and other groups. Diverse NF are available in different kinds of soil, especially in soils that contain high densities of nematodes. There is a relationship between the environment of nematodes and NF. NF can be divided into two types according to the mechanisms that affect nematodes. These types are divided into direct or indirect effects. The direct effects include the following: ectoparasites, endoparasites, cyst, or egg parasites producing toxins, and attack tools as special devices. However, the indirect effect comprises two groups: paralyzing toxins and the effect on the life cycle of nematodes. We explained the molecular mechanisms for determining the suitable conditions in brief and clarified the potential for increasing the efficacy of NF to highly impact sustainable agriculture in two ways: directly and indirectly.
An Integrated Regulatory Network of mRNAs, microRNAs, and lncRNAs Involved in Nitrogen Metabolism of Moso Bamboo
Authors: Yuan Tingting , Zhu Chenglei , Li Guangzhu , Liu Yan , Yang Kebin , Li Zhen , Song Xinzhang , Gao Zhimin
Published: May 2022

Nitrogen is a key macronutrient essential for plant growth and development, and its availability has a strong influence on biological processes. Nitrogen fertilizer has been widely applied in bamboo forests in recent decades; however, the mechanism of nitrogen metabolism in bamboo is not fully elucidated. Here, we characterized the morphological, physiological, and transcriptome changes of moso bamboo in response to different schemes for nitrogen addition to illuminate the regulation mechanism of nitrogen metabolism. The appropriate addition of nitrogen improved the chlorophyll content and Pn (net photosynthetic rate) of leaves, the nitrogen and ammonium contents of the seedling roots, the biomass of the whole seedling, the number of lateral roots, and the activity of enzymes involved in nitrogen metabolism in the roots. Based on the whole transcriptome data of the roots, a total of 8,632 differentially expressed mRNAs (DEGs) were identified under different nitrogen additions, such as 52 nitrate transporter genes, 6 nitrate reductase genes, 2 nitrite reductase genes, 2 glutamine synthase genes, 2 glutamate synthase genes (GOGAT), 3 glutamate dehydrogenase genes, and 431 TFs belonging to 23 families. Meanwhile, 123 differentially expressed miRNAs (DEMs) and 396 differentially expressed lncRNAs (DELs) were characterized as nitrogen responsive, respectively. Furthermore, 94 DEM-DEG pairs and 23 DEL-DEG pairs involved in nitrogen metabolism were identified. Finally, a predicted regulatory network of nitrogen metabolism was initially constructed, which included 17 nitrogen metabolic pathway genes, 15 TFs, 4 miRNAs, and 10 lncRNAs by conjoint analysis of DEGs, DEMs, and DELs and their regulatory relationships, which was supported by RNA-seq data and qPCR results. The lncRNA-miRNA-mRNA network provides new insights into the regulation mechanism of nitrogen metabolism in bamboo, which facilitates further genetic improvement for bamboo to adapt to the fluctuating nitrogen environment.
Meckel’s Cartilage in Mandibular Development and Dysmorphogenesis
Authors: Pitirri M. Kathleen , Durham Emily L. , Romano Natalie A. , Santos Jacob I. , Coupe Abigail P. , Zheng Hao , Chen Danny Z. , Kawasaki Kazuhiko , Jabs Ethylin Wang , Richtsmeier Joan T. , Wu Meng , Motch Perrine Susan M.
Published: May 2022

The Fgfr2cC342Y/+ Crouzon syndrome mouse model carries a cysteine to tyrosine substitution at amino acid position 342 (Cys342Tyr; C342Y) in the fibroblast growth factor receptor 2 (Fgfr2) gene equivalent to a FGFR2 mutation commonly associated with Crouzon and Pfeiffer syndromes in humans. The Fgfr2c C342Y mutation results in constitutive activation of the receptor and is associated with upregulation of osteogenic differentiation. Fgfr2cC342Y/+ Crouzon syndrome mice show premature closure of the coronal suture and other craniofacial anomalies including malocclusion of teeth, most likely due to abnormal craniofacial form. Malformation of the mandible can precipitate a plethora of complications including disrupting development of the upper jaw and palate, impediment of the airway, and alteration of occlusion necessary for proper mastication. The current paradigm of mandibular development assumes that Meckel’s cartilage (MC) serves as a support or model for mandibular bone formation and as a template for the later forming mandible. If valid, this implies a functional relationship between MC and the forming mandible, so mandibular dysmorphogenesis might be discerned in MC affecting the relationship between MC and mandibular bone. Here we investigate the relationship of MC to mandible development from the early mineralization of the mandible (E13.5) through the initiation of MC degradation at E17.7 using Fgfr2cC342Y/+ Crouzon syndrome embryos and their unaffected littermates (Fgfr2c+/+). Differences between genotypes in both MC and mandibular bone are subtle, however MC of Fgfr2cC342Y/+ embryos is generally longer relative to unaffected littermates at E15.5 with specific aspects remaining relatively large at E17.5. In contrast, mandibular bone is smaller overall in Fgfr2cC342Y/+ embryos relative to their unaffected littermates at E15.5 with the posterior aspect remaining relatively small at E17.5. At a cellular level, differences are identified between genotypes early (E13.5) followed by reduced proliferation in MC (E15.5) and in the forming mandible (E17.5) in Fgfr2cC342Y/+ embryos. Activation of the ERK pathways is reduced in the perichondrium of MC in Fgfr2cC342Y/+ embryos and increased in bone related cells at E15.5. These data reveal that the Fgfr2c C342Y mutation differentially affects cells by type, location, and developmental age indicating a complex set of changes in the cells that make up the lower jaw.
Potential of Polyethyleneimine as an Adjuvant To Prepare Long-Term and Potent Antifungal Nanovaccine
Authors: Jin Zhao , Dong Yi-Ting , Liu Shuang , Liu Jie , Qiu Xi-Ran , Zhang Yu , Zong Hui , Hou Wei-Tong , Guo Shi-Yu , Sun Yu-Fang , Chen Si-Min , Dong Hai-Qing , Li Yong-Yong , An Mao-Mao , Shen Hui
Published: May 2022

Background

Candida albicans infections are particularly prevalent in immunocompromised patients. Even with appropriate treatment with current antifungal drugs, the mortality rate of invasive candidiasis remains high. Many positive results have been achieved in the current vaccine development. There are also issues such as the vaccine’s protective effect is not persistent. Considering the functionality and cost of the vaccine, it is important to develop safe and efficient new vaccines with long-term effects. In this paper, an antifungal nanovaccine with Polyethyleneimine (PEI) as adjuvant was constructed, which could elicit more effective and long-term immunity via stimulating B cells to differentiate into long-lived plasma cells.

Materials and Methods

Hsp90-CTD is an important target for protective antibodies during disseminated candidiasis. Hsp90-CTD was used as the antigen, then introduced SDS to “charge” the protein and added PEI to form the nanovaccine. Dynamic light scattering and transmission electron microscope were conducted to identify the size distribution, zeta potential, and morphology of nanovaccine. The antibody titers in mice immunized with the nanovaccine were measured by ELISA. The activation and maturation of long-lived plasma cells in bone marrow by nanovaccine were also investigated via flow cytometry. Finally, the kidney of mice infected with Candida albicans was stained with H&E and PAS to evaluate the protective effect of antibody in serum produced by immunized mice.

Results

Nanoparticles (NP) formed by Hsp90-CTD and PEI are small, uniform, and stable. NP had an average size of 116.2 nm with a PDI of 0.13. After immunizing mice with the nanovaccine, it was found that the nano-group produced antibodies faster and for a longer time. After 12 months of immunization, mice still had high and low levels of antibodies in their bodies. Results showed that the nanovaccine could promote the differentiation of B cells into long-lived plasma cells and maintain the long-term existence of antibodies in vivo. After immunization, the antibodies in mice could protect the mice infected by C. albicans.

Conclusion

As an adjuvant, PEI can promote the differentiation of B cells into long-lived plasma cells to maintain long-term antibodies in vivo. This strategy can be adapted for the future design of vaccines.
Mechanisms Causing Acantholysis in Pemphigus-Lessons from Human Skin
Authors: Egu Desalegn Tadesse , Schmitt Thomas , Waschke Jens
Published: May 2022

Pemphigus vulgaris (PV) is an autoimmune bullous skin disease caused primarily by autoantibodies (PV-IgG) against the desmosomal adhesion proteins desmoglein (Dsg)1 and Dsg3. PV patient lesions are characterized by flaccid blisters and ultrastructurally by defined hallmarks including a reduction in desmosome number and size, formation of split desmosomes, as well as uncoupling of keratin filaments from desmosomes. The pathophysiology underlying the disease is known to involve several intracellular signaling pathways downstream of PV-IgG binding. Here, we summarize our studies in which we used transmission electron microscopy to characterize the roles of signaling pathways in the pathogenic effects of PV-IgG on desmosome ultrastructure in a human ex vivo skin model. Blister scores revealed inhibition of p38MAPK, ERK and PLC/Ca2+ to be protective in human epidermis. In contrast, inhibition of Src and PKC, which were shown to be protective in cell cultures and murine models, was not effective for human skin explants. The ultrastructural analysis revealed that for preventing skin blistering at least desmosome number (as modulated by ERK) or keratin filament insertion (as modulated by PLC/Ca2+) need to be ameliorated. Other pathways such as p38MAPK regulate desmosome number, size, and keratin insertion indicating that they control desmosome assembly and disassembly on different levels. Taken together, studies in human skin delineate target mechanisms for the treatment of pemphigus patients. In addition, ultrastructural analysis supports defining the specific role of a given signaling molecule in desmosome turnover at ultrastructural level.
Anti-HIV-1 Nanobody-IgG1 Constructs With Improved Neutralization Potency and the Ability to Mediate Fc Effector Functions
Authors: Schriek Angela I. , van Haaren Marlies M. , Poniman Meliawati , Dekkers Gillian , Bentlage Arthur E. H. , Grobben Marloes , Vidarsson Gestur , Sanders Rogier W. , Verrips Theo , Geijtenbeek Teunis B. H. , Heukers Raimond , Kootstra Neeltje A. , de Taeye Steven W. , van Gils Marit J.
Published: May 2022

The most effective treatment for HIV-1, antiretroviral therapy, suppresses viral replication and averts the disease from progression. Nonetheless, there is a need for alternative treatments as it requires daily administration with the possibility of side effects and occurrence of drug resistance. Broadly neutralizing antibodies or nanobodies targeting the HIV-1 envelope glycoprotein are explored as alternative treatment, since they mediate viral suppression and contribute to the elimination of virus-infected cells. Besides neutralization potency and breadth, Fc-mediated effector functions of bNAbs also contribute to thein vivoefficacy. In this study multivalent J3, 2E7 and 1F10 anti-HIV-1 broadly neutralizing nanobodies were generated to improve neutralization potency and IgG1 Fc fusion was utilized to gain Fc-mediated effector functions. Bivalent and trivalent nanobodies, coupled using long glycine-serine linkers, showed increased binding to the HIV-1 Env and enhanced neutralization potency compared to the monovalent variant. Fusion of an IgG1 Fc domain to J3 improved neutralization potency compared to the J3-bihead and restored Fc-mediated effector functions such as antibody-dependent cellular phagocytosis and trogocytosis, and natural killer cell activation. Due to their neutralization breadth and potency and their ability to induce effector functions these nanobody-IgG1 constructs may prove to be valuable towards alternative HIV-1 therapies.
Evaluation of a Human T Cell-Targeted Multi-Epitope Vaccine for Q Fever in Animal Models of Coxiella burnetii Immunity
Authors: Sluder Ann E. , Raju Paul Susan , Moise Leonard , Dold Christina , Richard Guilhem , Silva-Reyes Laura , Baeten Laurie A. , Scholzen Anja , Reeves Patrick M. , Pollard Andrew J. , Garritsen Anja , Bowen Richard A. , De Groot Anne S. , Rollier Christine , Poznansky Mark C.
Published: May 2022

T cell-mediated immunity plays a central role in the control and clearance of intracellular Coxiella burnetii infection, which can cause Q fever. Therefore, we aimed to develop a novel T cell-targeted vaccine that induces pathogen-specific cell-mediated immunity to protect against Q fever in humans while avoiding the reactogenicity of the current inactivated whole cell vaccine. Human HLA class II T cell epitopes from C. burnetii were previously identified and selected by immunoinformatic predictions of HLA binding, conservation in multiple C. burnetii isolates, and low potential for cross-reactivity with the human proteome or microbiome. Epitopes were selected for vaccine inclusion based on long-lived human T cell recall responses to corresponding peptides in individuals that had been naturally exposed to the bacterium during a 2007-2010 Q fever outbreak in the Netherlands. Multiple viral vector-based candidate vaccines were generated that express concatemers of selected epitope sequences arranged to minimize potential junctional neo-epitopes. The vaccine candidates caused no antigen-specific reactogenicity in a sensitized guinea pig model. A subset of the vaccine epitope peptides elicited antigenic recall responses in splenocytes from C57BL/6 mice previously infected with C. burnetii. However, immunogenicity of the vaccine candidates in C57BL/6 mice was dominated by a single epitope and this was insufficient to confer protection against an infection challenge, highlighting the limitations of assessing human-targeted vaccine candidates in murine models. The viral vector-based vaccine candidates induced antigen-specific T cell responses to a broader array of epitopes in cynomolgus macaques, establishing a foundation for future vaccine efficacy studies in this large animal model of C. burnetii infection.
Hepatic Metabolomics Analysis of Hybrid Grouper (Epinephelus fuscoguttatus♀×Epinephelus polyphekadion♂) Fed With Quercetin and Sodium Quercetin-5′-Sulfonates
Authors: Luo Jun , Amenyogbe Eric , Huang Jian-sheng , Chen Gang
Published: May 2022

Combining feeding trials and metabolomics analyses of tissues and biofluids could shed light on nutrient effects and changes in feed intake. In the present study, hybrid grouper (F1 hybrid Epinephelus fuscoguttatus♀×Epinephelus polyphekadion♂) was used as the marine fish model to quantify the impacts of quercetin and sodium quercetin-5′-sulfonates on serum biochemistry and the status of hepatic lipid accumulation and the changes of metabolites in the liver using ultra-performance liquid chromatography-electrospray triple quadrupole mass spectrometry (UPLC-QTRAP/MS/MS). The study shows that total protein, albumin, alkaline phosphatase and glucose were not significantly different among the three groups (P > 0.05). Total cholesterol, triglyceride, and alanine aminotransferase of fish fed quercetin, and sodium quercetin-5′-sulfonates were significantly lower than fish fed without additives (P < 0.05). Low-density lipoprotein cholesterol and aspartate aminotransferase of fish fed quercetin were significantly lower than that of fish fed without additives and sodium quercetin-5′-sulfonates (P < 0.05). The high-density lipoprotein cholesterol of fish fed quercetin, and sodium quercetin-5′-sulfonates were significantly higher than that of fish fed without additives (P < 0.05). Lipid accumulation in the quercetin and sodium quercetin-5′-sulfonates groups decreased significantly. Quercetin and sodium quercetin-5′-sulfonates were effective by increasing hypolipidemic and hepatoprotective compounds that are known for reducing blood lipid levels and liver fat accumulation. As a result of this study, we provide international data for metabolic adaptations during the additives feeding using the fish liver as the study model. By understanding the metabolic effects of these feed additives, this study provides a first step toward understanding the molecular mechanisms of these additives and how they function.
Hypoxia Stress Induces Tissue Damage, Immune Defense, and Oxygen Transport Change in Gill of Silver Carp (Hypophthalmichthys molitrix): Evaluation on Hypoxia by Using Transcriptomics
Authors: Li Xiaohui , Ling Chen , Wang Qiaoxin , Feng Cui , Luo Xiangzhong , Sha Hang , He Guoyu , Zou Guiwei , Liang Hongwei
Published: May 2022

The silver carp (Hypophthalmichthys molitrix) is an economically, as well as environmentally, important fish that harbors low environmental hypoxia tolerance and frequently contributes to a loss of aquaculture productivity. The gill is the first tissue attacked by hypoxia; however, the response of the gills of H. molitrix to hypoxia stress at the tissue, cellular, and molecular levels has not been clearly established. The influence of hypoxia on histological features along with gene expression in silver carp gills were explored in this research. The hematoxylin and eosin-stained sections and electron microscopy examinations of gills indicated that the gill lamellae were seriously twisted, gill filaments were dehisced, and the swelling and shedding of epithelial cell layer in the gill tissue were intensified along with the degree of hypoxia. In the hypoxia, semi-asphyxia, and asphyxia groups, the gill transcriptomic assessment of shifts in key genes, as well as modulatory networks in response to hypoxic conditions revealed 587, 725, and 748 differentially expressed genes, respectively. These genes are abundant in immune response signaling cascades (e.g., complement and coagulation cascades, Nucleotide-binding and oligomerization domain (NOD)-like receptor signaling cascade, and differentiation of Th1 along with Th2 cells) and oxygen transport [e.g., MAPK, PI3K-Akt, and hypoxia-inducible factor 1 (HIF-1) signaling cascades]. Genes linked to immune response (e.g., c2, c3, c6, klf4, cxcr4, cd45, and cd40) and oxygen transport (e.g., egln1, egln3, epo, ldh, and vegfa) were additionally identified. According to our findings, the silver carp may be using “HIF-1” to obtain additional oxygen during hypoxia. These findings illustrate that hypoxia stress might damage gill tissue, trigger an immunological response, and activate HIF-1 signaling to increase oxygen availability under hypoxic situations. The findings of this work will help scientists better understand the molecular mechanisms driving hypoxia responses in hypoxia-sensitive fish and speed up the development of hypoxia-resistant varieties.
Case Report: Multimodal Imaging in a Rare Case of Morning Glory Disc Anomaly Complicated With Choroidal Ossification
Authors: Wang Shuya , Wang Xingrong , Wang Ying , Bi Hongsheng
Published: May 2022

Purpose

The authors described a 7-year-old boy who was diagnosed with morning glory disc (MGD) anomaly in the right eye via fundus examination. However, during the head CT examination, a hyperdense choroidal lesion was discovered around the optic disc. Comprehensive investigations revealed that the lesion's characteristics were extremely consistent with choroidal osteoma (CO), so the patient was diagnosed with MGD with CO on his second visit. However, in the subsequent follow-up, the author discovered pigmentary alterations in the retinal pigment epithelium (RPE) in the patient's right eye. Finally, the diagnosis was corrected to MGD with choroidal ossification following a thorough etiological analysis. Meanwhile, the characteristics of choroidal ossification were described in detail through multimodal imaging in this article.

Methods

Retrospective review of a case note.

Conclusions

Similar to CO, choroidal ossification is the consequence of structured osseous tissue formation regulated by osteoblasts and osteoclasts. It consists of bone trabecular and vascular components and is difficult to be distinguished from CO on imaging examinations. In contrast to the congenital prevalence of CO, there are often incentives for the occurrence of choroidal ossification. These inducements will eventually mediate the inflammation in the eye, resulting in the activation of many cytokines and the production of choroidal ossification. Around one-third of patients with MGD will experience retinal detachment, and in certain cases, the subretinal fluid will be absorbed spontaneously, resulting in alterations to the RPE. These processes can activate inflammatory factors in the eye, bringing about a cascade of abnormalities, including the development of CO. Therefore, the proper diagnosis of disease should not be made exclusively on the basis of the imaging findings. A thorough analysis of the epidemiology and etiology is crucial.
Cardiovascular Risk in Patients With Takayasu Arteritis Directly Correlates With Diastolic Dysfunction and Inflammatory Cell Infiltration in the Vessel Wall: A Clinical, ex vivo and in vitro Analysis
Authors: Cicco Sebastiano , Desantis Vanessa , Vacca Antonio , Cazzato Gerardo , Solimando Antonio G. , Cirulli Anna , Noviello Silvia , Susca Cecilia , Prete Marcella , Brosolo Gabriele , Catena Cristiana , Lamanuzzi Aurelia , Saltarella Ilaria , Frassanito Maria Antonia , Cimmino Antonella , Ingravallo Giuseppe , Resta Leonardo , Ria Roberto , Montagnani Monica
Published: May 2022

Background

Takayasu Arteritis (TAK) increases vascular stiffness and arterial resistance. Atherosclerosis leads to similar changes. We investigated possible differences in cardiovascular remodeling between these diseases and whether the differences are correlated with immune cell expression.

Methods

Patients with active TAK arteritis were compared with age- and sex-matched atherosclerotic patients (Controls). In a subpopulation of TAK patients, Treg/Th17 cells were measured before (T0) and after 18 months (T18) of infliximab treatment. Echocardiogram, supraaortic Doppler ultrasound, and lymphocytogram were performed in all patients. Histological and immunohistochemical changes of the vessel wall were evaluated as well.

Results

TAK patients have increased aortic valve dysfunction and diastolic dysfunction. The degree of dysfunction appears associated with uric acid levels. A significant increase in aortic stiffness was also observed and associated with levels of peripheral T lymphocytes. CD3+ CD4+ cell infiltrates were detected in the vessel wall samples of TAK patients, whose mean percentage of Tregs was lower than Controls at T0, but increased significantly at T18. Opposite behavior was observed for Th17 cells. Finally, TAK patients were found to have an increased risk of atherosclerotic cardiovascular disease (ASCVD).

Conclusion

Our data suggest that different pathogenic mechanisms underlie vessel damage, including atherosclerosis, in TAK patients compared with Controls. The increased risk of ASCVD in TAK patients correlates directly with the degree of inflammatory cell infiltration in the vessel wall. Infliximab restores the normal frequency of Tregs/Th17 in TAK patients and allows a possible reduction of steroids and immunosuppressants.