bluuebunny/crossref_metadata_2025 huggingface dataset:
Crustal deformation and dynamics of the south-eastern tibetan plateau from stress fields and geodesy
Authors: Wang Kaiying , Feng Xiangdong
Published: September 2022

South-eastern Tibet rotates clockwise around the eastern Himalayan syntaxis due to the eastward extrusion of the eastern Tibetan lithosphere and it attracts much attention as a window for studying the dynamics of continental collision between India and Eurasia. Competing geodynamic models to describe the deformation of the eastern Tibet have been the debating subject and the dynamic processes responsible for plateau evolution remain poorly understood, partly because the mechanical state at depth and its relationship with surficial deformation are unclear. In this context, a continuous east-west oriented tensional zone was identified at the south-eastern edge of the Tibetan Plateau based on seismogenic stress field and global positioning system data. The profiles of surficial velocity field reveal a relatively speedy motion belt parallel to the Xianshuihe fault extending from north to south in the rotating region east of the tensional zone. Segmented features of the profiles around the extensional zone indicate its close relation with flow channels delineated from magnetotelluric images. Therefore, the deformation at the south-eastern edge of the Tibetan Plateau is mechanically coupled within the crustal depth. We propose a complex regional kinematics with a localised speedy belt and a continuously extensional zone, where material coupling and deformation compatibility were revealed within the crustal depth.
Sensitivity of boundary layer schemes in simulating the asymmetric rainfall of landfalling typhoon Lekima (2019)
Authors: Duan Jingjing , Yu Zifeng , Hu Bo , Zhen Yan , Cheung Kevin K. W. , Li Yubin , Cai Zhiying
Published: September 2022

A group of control (CTL) plus ten sensitivity numerical experiments have been conducted to investigate the sensitivity of planetary boundary layer (PBL) schemes in simulating the asymmetric precipitation distribution of typhoon Lekima (2019) during landfall. The simulated track and intensity are quite sensitive to the choice of the PBL scheme. In CTL that applies the Mellor–Yamada Nakanishi and Niino (MYNN) PBL and the surface layer scheme, the observed eyewall replacement 6 h prior to landfall and the asymmetric precipitation during landfall have been simulated well. However, in the PBL1 experiment that applies the Yonsei University (YSU) PBL scheme and the Revised Mesoscale Model version 5 (MM5) Monin–Obukhov surface layer scheme, no double eyewall is simulated. PBL1 and the other sensitivity experiments also simulate more axisymmetric precipitation distribution. PBL1 simulates intensification just before landfall, sustains intensity longer after landfall, but then dissipates quite rapidly. Such differences from CTL are due to larger enthalpy flux, higher PBL height (which is almost unchanged in CTL), and eddy diffusivity extending more into the free atmosphere in PBL1. These factors lead to outward expansion of the radius of maximum wind, larger radial inflow, larger axisymmetric tangential wind in the boundary layer, and larger updrafts in the eyewall. After landfall, larger momentum flux and larger friction velocity in PBL1 enable the more rapid dissipation. The intensification before landfall in PBL1 makes the axisymmetric component stronger. Asymmetry developed in the outer eyewall, and PBL1 was less successful in simulating the eyewall replacement that affects the degree of rainfall asymmetry. These results indicate that the model PBL schemes largely influence the simulated tropical cyclone (TC) intensity and structure including asymmetric rainfall distribution during landfall.
Developing an online system to support algebra progress monitoring: Teacher use and feedback
Authors: Stecker Pamela M. , Foegen Anne
Published: September 2022

A brief overview of the development of an online system to support algebra progress monitoring across several years of an iterative process of development, feedback, and revision is provided. Online instructional modules addressed progress monitoring concepts and procedures; administration and scoring of three types of algebra measures, including teacher accuracy with scoring; and navigation and use of the online data management system, including data entry, graphing, and skills analyses. In the final year of this federally funded research project, a test of the functionality of the completed system as well as an evaluation of teachers’ knowledge, accuracy, and satisfaction with the online professional development was evaluated. Specifically, 29 general and special education secondary school teachers completed 11 fully developed online instructional modules independently and administered weekly two of three types of algebra measures across 10 weeks with one of their classes of students. Data analysis included teacher accuracy in the scoring of the measures; change in their knowledge of student progress monitoring and data-based decision making; and teacher satisfaction with the online system, including instructional content, feasibility, and usability for data-based decision making. Directions for future research and implications for classroom use of this online system are discussed.
The effect of Chinese herbal formulas combined with metformin on modulating the gut microbiota in the amelioration of type 2 diabetes mellitus: A systematic review and meta-analysis
Authors: Xu Yunxi , Zheng Shuyu , Jiang Shui , Chen Junyu , Zhu Xiaofang , Zhang Ya
Published: September 2022

To assess and analyse the effectiveness and safety of combined Chinese herbal formula (CHF) and metformin treatment in the modulation of the gut microbiota in the amelioration of type 2 diabetes mellitus(T2DM), all publications addressing the effect of this combination treatment on the quantitative alterations in the gut microbiota and glucose parameters were collected. Rob tool in the Cochrane handbook was performed to evaluate the methodological quality of all included studies. Relevant information and statistics were abstracted and synthesized in Review Manager 5.4 to evaluate the efficacy of combination treatment. Sensitivity analyses and subgroup analyses were used to analyse the sources of heterogeneity. Publication bias analyses were performed by Stata software to assess the robustness and quality of the outcomes. As a result, a total of 12 eligible RCTs with 1307 T2DM participants from 7 electronic databases were included. Combined CHF with metformin treatment showed better efficacies than metformin monotherapy in regulating the structure of the gut microbiota, characterized by increased Bifidobacterium, Lactobacillus and Bacteroidetes and decreased Enterobacteriaceae, Enterococcus, and Saccharomyces along with better decreases in glycated haemoglobin, fasting plasma glucose, 2-hour postprandial blood glucose, fasting insulin and homeostasis model assessment of insulin resistance. Subgroup analyses further analysed the effect of metformin doses and CHF classifications on controlling hyperglycaemia and altering the gut microbiota. In conclusion, our meta-analysis suggested that combined CHF with metformin treatment is promising for the modulation of the gut microbiota along with ameliorating hyperglycemia in T2DM patients. Importantly, more well-designed RCTs are needed to validate the outcomes and verify the treatment value for clinical purposes.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021291524, identifier CRD42021291524.
Dietary organosulfur compounds: Emerging players in the regulation of bone homeostasis by plant-derived molecules
Authors: Gambari Laura , Grigolo Brunella , Grassi Francesco
Published: September 2022

The progressive decline of bone mass and the deterioration of bone microarchitecture are hallmarks of the bone aging. The resulting increase in bone fragility is the leading cause of bone fractures, a major cause of disability. As the frontline pharmacological treatments for osteoporosis suffer from low patients’ adherence and occasional side effects, the importance of diet regimens for the prevention of excessive bone fragility has been increasingly recognized. Indeed, certain diet components have been already associated to a reduced fracture risk. Organosulfur compounds are a broad class of molecules containing sulfur. Among them, several molecules of potential therapeutic interest are found in edible plants belonging to theAlliumandBrassicabotanical genera. Polysulfides derived fromAlliaceaeand isothiocyanates derived fromBrassicaceaehold remarkable nutraceutical potential as anti-inflammatory, antioxidants, vasorelaxant and hypolipemic. Some of these effects are linked to the ability to release the gasotrasmitter hydrogen sulfide (H2S). Recent preclinical studies have investigated the effect of organosulfur compounds in bone wasting and metabolic bone diseases, revealing a strong potential to preserve skeletal health by exerting cytoprotection and stimulating the bone forming activity by osteoblasts and attenuating bone resorption by osteoclasts. This review is intended for revising evidence from preclinical and epidemiological studies on the skeletal effects of organosulfur molecules of dietary origin, with emphasis on the direct regulation of bone cells by plant-derived polysulfides, glucosinolates and isothiocyanates. Moreover, we highlight the potential molecular mechanisms underlying the biological role of these compounds and revise the importance of the so-called ‘H2S-system’ on the regulation of bone homeostasis.
Flour derived porous carbon as anode for highly robust potassium-ion batteries
Authors: Liu Yong , Gong Zhen , Li Liqing
Published: September 2022

Potassium-ion batteries (PIBs) have attracted increasing research interest because of the natural abundance and low cost of potassium. Nevertheless, lacking of suitable anode materials that can deliver high reversible capacity and long cycle life highly hinder the further development of PIBs. Here, we report a flour chemistry strategy to establish a porous phosphorus-doped carbon (PPDC) as anode for high-performance PIBs. The as-prepared PPDC with high hierarchically porous structure and rich P-doping not only offers fast transport of K+ and electrons during continuous cycling, but also affords sufficient inner space to relieve volume expansion of active electrode. Therefore, the PPDC displayed high reversible capacity, excellent cyclic stability, outstanding rate performance. These results imply a great potential for applications in the field of high-energy storage devices.
Super-resolution perception for wind power forecasting by enhancing historical data
Authors: Liu Guolong , Zhang Shuwen , Zhao Huan , Liu Jinjie , Liang Gaoqi , Zhao Junhua , Sun Guangzhong
Published: September 2022

As an important part of renewable energy, wind power is crucial to the realization of carbon neutrality. It is worth studying on how to accurately predict the wind output so that it can be integrated into the power grid as much as possible to enhance its utilization rate. In this article, a data enhancement method and a framework are proposed to assist wind power forecasting. The proposed method uses the super-resolution perception technology to first detect the completeness and correctness of historical meteorological and wind power data collected by industrial devices. Then, the detected errors are corrected and the missing data are recovered to make the data complete. The frequency of the data is then increased using the proposed method so that the data become complete high-frequency data. Based on the enhanced complete high-frequency data with more detailed characteristics, more accurate forecasts of wind power can be achieved, thereby improving the utilization rate of wind power. Experiments based on public datasets are used to demonstrate the effectiveness of the proposed method and framework. With the proposed method and framework, higher frequency data with more detailed information can be achieved, thereby providing support for accurate wind power prediction that was not possible before.
A dual input single output non-isolated DC-DC converter for multiple sources electric vehicle applications
Authors: Karthikeyan B , Sundararaju K , Palanisamy R , Manivasagam R , Hossain Ismail , Bajaj Mohit , Shouran Mokhtar , Abdul samad Bdereddin , Kamel Salah
Published: September 2022

There is a need to design DC-DC converters capable of handling high voltages and that employ single-stage conversion to integrate renewable energy resources, such as solar photovoltaic cells and fuel cells, for electric vehicle applications. This paper elucidates the design and analysis of a dual input single output non-isolated Cuk-derived converter with a high step-up ratio. The proposed converter can effectively handle two different energy resources that have different electrical characteristics. It makes use of one common inductor between the dual input port, which reduces the passive components and the circuit volume required. The maximum efficiency that can be achieved by this converter is 95.72%, with two main switches and one diode in the circuit. This study involved a detailed analysis of the proposed converter in continuous current operation mode. A continuous current with reduced ripple in the output improves a fuel cell’s operating life-span. The efficacy of the proposed converter is verified through simulation and validated by constructing a 200 W, real-time, scaled-down prototype model.
Climatic influences on intra-annual stem variation of Larix principis-rupprechtii in a semi-arid region
Authors: Li Weixin , Yue Fengxin , Wang Chunkai , Liao Jinglei , Zhang Xianliang
Published: September 2022

Intra-annual monitoring of stem radial growth dynamics of trees and detecting how tree growth responds to changing climatic conditions are crucial for predicting the future growth dynamics under increasing drought conditions. Here, we monitored the intra-annual stem radial growth dynamics of seven Larix principis-rupprechtii using point dendrometers to investigate the influence of climate variables on the intra-annual growth of L. principis-rupprechtii in the growing season. The average stem radial growth of L. principis-rupprechtii started on 29 April and stopped on 17 August based on the sigmoid Gompertz functions. The intra-annual stem radial growth of L. principis-rupprechtii showed a parabolic trend, with its growth decreased when the temperature and sunlight duration hours exceeded certain thresholds. The vapor pressure deficits (VPD) strongly influenced tree intra-annual growth over other climatic factors in the growing season. Stem radial growth of L. principis-rupprechtii decreased significantly with increasing VPD when VPD ranged from 0.5 to 0.8 kPa. Intra-annual stem radial growth of L. principis-rupprechtii was severely inhibited when VPD was higher than 0.8 kPa. In contrast, tree stem radial growth reached the maximum when VPD was lower than 0.5 kPa. Our study highlighted the important influences of major limiting climatic factors on the stem radial growth of trees in semi-arid regions.
Economic evaluation of using polygenic risk score to guide risk screening and interventions for the prevention of type 2 diabetes in individuals with high overall baseline risk
Authors: Martikainen Janne , Lehtimäki Aku-Ville , Jalkanen Kari , Lavikainen Piia , Paajanen Teemu , Marjonen Heidi , Kristiansson Kati , Lindström Jaana , Perola Markus
Published: September 2022

Type 2 diabetes (T2D) with increasing prevalence is a significant global public health challenge. Obesity, unhealthy diet, and low physical activity are one of the major determinants of the rise in T2D prevalence. In addition, family history and genetic risk of diabetes also play a role in the process of developing T2D. Therefore, solutions for the early identification of individuals at high risk for T2D for early targeted detection of T2D, prevention, and intervention are highly preferred. Recently, novel genomic-based polygenic risk scores (PRSs) have been suggested to improve the accuracy of risk prediction supporting the targeting of preventive interventions to those at highest risk for T2D. Therefore, the aim of the present study was to assess the cost-utility of an additional PRS testing information (as a part of overall risk assessment) followed by a lifestyle intervention and an additional medical therapy when estimated 10-year overall risk for T2D exceeded 20% among Finnish individuals screened as at the high-risk category (i.e., 10%–20% 10-year overall risk of T2D) based on traditional risk factors only. For a cost-utility analysis, an individual-level state-transition model with probabilistic sensitivity analysis was constructed. A 1-year cycle length and a lifetime time horizon were applied in the base-case. A 3% discount rate was used for costs and QALYs. Cost-effectiveness acceptability curve (CEAC) and estimates for the expected value of perfect information (EVPI) were calculated to assist decision makers. The use of the targeted PRS strategy reclassified 12.4 percentage points of individuals to be very high-risk individuals who would have been originally classified as high risk using the usual strategy only. Over a lifetime horizon, the targeted PRS was a dominant strategy (i.e., less costly, more effective). One-way and scenario sensitivity analyses showed that results remained dominant in almost all simulations. However, there is uncertainty, since the probability (EVPI) of cost-effectiveness at a WTP of 0€/QALY was 63.0% (243€) indicating the probability that the PRS strategy is a dominant option. In conclusion, the results demonstrated that the PRS provides moderate additional value in Finnish population in risk screening leading to potential cost savings and better quality of life when compared with the current screening methods for T2D risk.
Analysis of genomes and transcriptomes of clear cell renal cell carcinomas identifies mutations and gene expression changes in the TGF-beta pathway
Authors: Che Xiangyu , Li Jianyi , Xu Yingkun , Wang Qifei , Wu Guangzhen
Published: September 2022

The occurrence of clear cell renal cell carcinoma (ccRCC) is related to changes in the transforming growth factor-β (TGF-β) signaling pathway. In this study, we adopted an integrated approach to identify and verify the effects of changes in this pathway on ccRCC and provide a guide for identifying new therapeutic targets. We performed transcriptome analysis of 539 ccRCC cases from The Cancer Genome Atlas (TCGA) and divided the samples into different TGF-β clusters according to unsupervised hierarchical clustering. We found that 76 of the 85 TGF-β pathway genes were dysregulated, and 55 genes were either protective or risk factors affecting the prognosis of ccRCC. The survival time of patients with tumors with low TGF-β scores was shorter than that of patients with tumors with high TGF-β scores. The overall survival (OS) of patients with ccRCC with high TGF-β scores was better than that of patients with low TGF-β scores. The TGF-β score correlated with the expression of key ccRCC and deacetylation genes. The sensitivity of tumor patients to targeted drugs differed between the high and low TGF-β score groups. Therefore, a prognostic model based on the TGF-β gene pathway can predict the prognosis of ccRCC patients. Grouping patients with ccRCC according to their TGF-β score is of great significance for evaluating the prognosis of patients, selecting targeted drugs, and identifying new therapeutic targets.
Cross-talk between necroptosis-related lncRNAs to construct a novel signature and predict the immune landscape of lung adenocarcinoma patients
Authors: Wu Jie , Song Dingli , Zhao Guang , Chen Sisi , Ren Hong , Zhang Boxiang
Published: September 2022

Background: As a new style of cell death, necroptosis plays a crucial role in tumor immune microenvironment. LncRNAs have been identified to act as competitive RNAs to influence genes involved in necroptosis. Therefore, we aim to create a signature based on necroptosis-related lncRNAs to predict the prognosis and immune landscape of lung adenocarcinoma (LUAD) patients in this study.

Methods: TCGA database was used to acquire RNA sequencing (RNA-Seq) data and clinical information for 59 lung normal samples and 535 lung adenocarcinoma samples. The Pearson correlation analysis, univariate cox regression analysis and least absolute shrinkage and selection operator (LASSO) cox regression were performed to construct the prognostic NRlncRNAs signature. Then we used Kaplan-Meier (K-M) analysis, time-dependent ROC curves, univariate and multivariate cox regression analysis, and nomogram to validate this signature. In addition, GO, KEGG, and GSVA were analyzed to investigate the potential molecular mechanism. Moreover, we analyzed the relationship between our identified signature and immune microenvironment, TMB, and some clinical characteristics. Finally, we detected the expression of the six necroptosis-related lncRNAs in cells and tissues.

Results: We constructed a NRlncRNAs signature consisting of six lncRNAs (FRMD6-AS1, LINC01480, FAM83A-AS1, FRMD6-AS1, MED4-AS1, and LINC01415) in LUAD. LUAD patients with high risk scores had lower chance of survival with an AUC of 0.739, 0.709, and 0.733 for 1-year, 3-year, and 5-year respectively. The results based on GO, KEGG, and GSVA enrichment analysis demonstrated that NRlncRNAs signature-related genes were mainly correlated with immune pathways, metabolic-and cell growth-related pathways, cell cycle, and apoptosis. Moreover, the risk score was correlated with the immune status of LUAD patients. Patients with higher risk scores had lower ESTIMATE scores and higher TIDE scores. The risk score was positively correlated with TMB. LINC01415, FRMD6-AS1 and FAM83A-AS1 were significantly overexpressed in lung adenocarcinoma, while the expression levels of MED4-AS1 and LINC01480 were lower in lung adenocarcinoma.

Conclusion: Overall, an innovative prognostic signature based on NRlncRNAs was developed for LUAD through comprehensive bioinformatics analysis, which can act as a predictor of immunotherapy and may provide guidance for clinicians.
Clec7a expression in inflammatory macrophages orchestrates progression of acute kidney injury
Authors: Wang Yaqiong , Li Xianzhe , Xu Xialian , Yu Jinbo , Chen Xiaohong , Cao Xuesen , Zou Jianzhou , Shen Bo , Ding Xiaoqiang
Published: September 2022

Acute kidney injury (AKI) is associated with high risk of mortality, post-disease renal fibrosis, kidney dysfunction and renal failure. Renal macrophages play a key role in the pathogenesis (M1 subpopulation), healing and remodeling (M2 subpopulation) in AKI and, thus, have been a promising target for clinical treatment of AKI. Here, in a mouse renal ischemia/reperfusion injury (IRI) model for AKI, we showed that renal macrophages could be further classified into Clec7a+ M1 macrophages, Clec7a- M1 macrophages, Clec7a+ M2 macrophages and Clec7a- M2 macrophages, representing distinct macrophage populations with different functionality. Interestingly, Clec7a+ M1 macrophages exhibited potent pro-inflammatory and phagocytic effects compared to Clec7a- M1 macrophages, while Clec7a- M2 macrophages exhibited better proliferating and migrating potential, which is critical for their role in tissue repairing after injury. These data from mice were further strengthened by bioinformatics analyses using published database. In vivo, combined expression of Clec7a in M1 macrophages and depletion of Clec7a in M2 macrophages significantly improved the renal function after IRI-AKI. Together, our data suggest that Clec7a is crucial for the fine regulation of macrophage phenotype during AKI and could be a novel target for boosting clinical therapy.
Temperature induces metabolic reprogramming in fish during bacterial infection
Authors: Sun Bin , Sun Boguang , Zhang Beibei , Sun Li
Published: September 2022

Water temperature elevation as a consequence of global warming results in increased incidence of bacterial disease, such as edwardsiellosis, in fish farming. Edwardsiellosis is caused by the bacterial pathogen Edwardsiella tarda and affects many farmed fish including flounder (Paralichthys olivaceus). Currently, the effect of temperature on the metabolic response of flounder to E. tarda infection is unclear. In this study, we found that compared to low temperature (15°C), high temperature (23°C) enhanced E. tarda dissemination in flounder tissues. To examine the impact of temperature on the metabolism of flounder induced by E. tarda, comparative metabolomics were performed, which identified a large number of metabolites responsive to E. tarda invasion and temperature alteration. During E. tarda infection, the metabolic profile induced by elevated temperature was mainly featured by extensively decreased amino acids and TCA intermediates such as succinate, a proven immune regulator. Further, 38 potential metabolite markers of temperature effect (MMTE) in association with bacterial infection were identified. When used as exogenous supplements, two of the MMTE, i.e., L-methionine and UDP-glucose, effectively upregulated the expression of pro-inflammatory cytokines and suppressed E. tarda infection in flounder leukocytes. Taken together, the results of this study indicate an important influence of temperature on the metabolism of flounder during bacterial infection, which eventually affects the survivability of the fish.
Site-specific N-glycosylation characterization of micro monoclonal immunoglobulins based on EThcD-sceHCD-MS/MS
Authors: Luo Mengqi , Mao Yonghong , Zeng Wenjuan , Zheng Shanshan , Li Huixian , Hu Juanjuan , Xie Xinfang , Zhang Yong
Published: September 2022

Monoclonal immunoglobulin produced by clonal plasma cells is the main cause in multiple myeloma and monoclonal gammopathy of renal significance. Because of the complicated purification method and the low stoichiometry of purified protein and glycans, site-specific N-glycosylation characterization for monoclonal immunoglobulin is still challenging. To profile the site-specific N-glycosylation of monoclonal immunoglobulins is of great interest. Therefore, in this study, we presented an integrated workflow for micro monoclonal IgA and IgG purification from patients with multiple myeloma in the HYDRASYS system, in-agarose-gel digestion, LC-MS/MS analysis without intact N-glycopeptide enrichment, and compared the identification performance of different mass spectrometry dissociation methods (EThcD-sceHCD, sceHCD, EThcD and sceHCD-pd-ETD). The results showed that EThcD-sceHCD was a better choice for site-specific N-glycosylation characterization of micro in-agarose-gel immunoglobulins (~2 μg) because it can cover more unique intact N-glycopeptides (37 and 50 intact N-glycopeptides from IgA1 and IgG2, respectively) and provide more high-quality spectra than sceHCD, EThcD and sceHCD-pd-ETD. We demonstrated the benefits of the alternative strategy in site-specific N-glycosylation characterizing micro monoclonal immunoglobulins obtained from bands separated by electrophoresis. This work could promote the development of clinical N-glycoproteomics and related immunology.
Blau syndrome: Lessons learned in a tertiary care centre at Chandigarh, North India
Authors: Kumrah Rajni , Pilania Rakesh Kumar , Menia Nitin Kumar , Rawat Amit , Sharma Jyoti , Gupta Anju , Vignesh Pandiarajan , Jindal Ankur Kumar , Rikhi Rashmi , Agarwal Aniruddha , Gupta Vishali , Singh Surjit , Suri Deepti
Published: September 2022

Objectives

Blau syndrome (BS) is a rare autoinflammatory disease characterized by arthritis, dermatitis, and granulomatous uveitis in early childhood. The study presents the clinical experience of patients with BS at a tertiary care centre in Chandigarh, North India.

Methods

Analysis of the clinical profile of patients of BS with NOD2 gene mutations under follow-up was carried out.

Results

Diagnosis of BS was genetically confirmed in 11 patients (10 children and one adult; six male and five female patients) from 10 families. The median age of onset of symptoms was 12 months (range, 4 months–4 years), while the age at diagnosis ranged from 2.3 to 26 years. The classic triad of arthritis, dermatitis, and uveitis was present in 6/11 (54.5%) patients. The frequency of arthritis, dermatitis, and uveitis was 100%, 81.8%, and 72.7%, respectively. The median age at diagnosis of ocular symptoms was 4 years (range, 2–26 years). Family history was noted in six families. Renal involvement was observed in two children. All patients in our cohort had the R334W variant in NOD2 gene. An asymptomatic carrier sibling with R334W mutation was identified in one family. Methotrexate was used as a first-line agent in all children. Adalimumab, which was commenced in five patients with uveitis, resulted in significant improvement in four patients. The total follow-up duration of the present cohort is 1,063.8 patient-months.

Conclusions

The possibility of BS should always be considered in patients with arthritis and early ocular involvement. Uveitis is often progressive and refractory to currently available therapies. Systemic involvement appears to remain a significant cause of morbidity and mortality.
Identification of novel B-1 transitional progenitors by B-1 lymphocyte fate-mapping transgenic mouse model Bhlhe41dTomato-Cre
Authors: Li Hui , Tang Yangyang , Ren Jinfeng , Bai Ruixue , Hu Lang , Jia Wenyu , Cao Yiwei , Hong Li , Xu Meizhen , Gao Sijia , Shi Yanbiao , Pan Shuai , Wang Liang , Zheng Kuiyang , Zhao Shuli , Wang Hui
Published: September 2022

B-1 lymphocytes exhibit specialized roles in host defense against multiple pathogens. Despite the fact that CD19+CD93+B220lo/-B cells have been identified as B-1 progenitors, the definition for B-1 progenitors remains to be elucidated as CD19+CD93+B220+B cells are capable to give rise to B-1 cells. Given that transcription factor Bhlhe41 is highly and preferentially expressed in B-1 cells and regulates B-1a cell development, we generated a transgenic mouse model,Bhlhe41dTomato-Cre, for fate mapping and functional analysis of B-1 cells.Bhlhe41dTomato-Cremice efficiently traced Bhlhe41 expression, which was mainly restricted to B-1 cells in B-cell lineage. We showed an efficient and specific Cre-mediated DNA recombination in adult B-1 cells and neonatal B-1 progenitors rather than B-2 cells by flow cytometric analysis ofBhlhe41dTomato-Cre/+Rosa26EYFPmice. Treatment ofBhlhe41dTomato-Cre/+Rosa26iDTRmice with diphtheria toxin revealed a robust efficacy of B-1 cell depletion. Interestingly, usingBhlhe41dTomato-Cremice, we demonstrated that neonatal B-1 progenitors (CD19+CD93+B220lo/-) expressed Bhlhe41 and were identical to well-defined transitional B-1a progenitors (CD19+CD93+B220lo/-CD5+), which only gave rise to peritoneal B-1a cells. Moreover, we identified a novel population of neonatal splenic CD19hidTomato+B220hiCD43loCD5loB cells, which differentiated to peritoneal B-1a and B-1b cells.Bhlhe41deficiency impaired the balance between CD19hidTomato+B220lo/-CD5hiand CD19hidTomato+B220hiCD5locells. Hence, we identified neonatal CD19hidTomato+B220hiCD43loCD5loB cells as novel transitional B-1 progenitors.Bhlhe41dTomato-Cre/+mouse can be used for fate mapping and functional studies of B-1 cells in host-immune responses.
Increased platelet activation and platelet-inflammasome engagement during chikungunya infection
Authors: Gomes de Azevedo-Quintanilha Isaclaudia , Campos Mariana Macedo , Teixeira Monteiro Ana Paula , Dantas do Nascimento Alessandra , Calheiros Andrea Surrage , Oliveira Douglas Mathias , Dias Suelen Silva Gomes , Soares Vinicius Cardoso , Santos Julia da Cunha , Tavares Isabel , Lopes Souza Thiago Moreno , Hottz Eugenio D. , Bozza Fernando A. , Bozza Patricia T.
Published: September 2022

Chikungunya fever is a viral disease transmitted by mosquitoes of the genus Aedes. The infection is usually symptomatic and most common symptoms are fever accompanied by joint pain and swelling. In most cases symptoms subside within a week. However, severe prolonged and disabling joint pain, that may persist for several months, even years, are reported. Although the pathogenesis of Chikungunya infection is not fully understood, the evolution to severe disease seems to be associated with the activation of immune mechanisms and the action of inflammatory mediators. Platelets are recognized as inflammatory cells with fundamental activities in the immune response, maintenance of vascular stability and pathogenicity of several inflammatory and infectious diseases. Although the involvement of platelets in the pathogenesis of viral diseases has gained attention in recent years, their activation in Chikungunya has not been explored. The aim of this study was to analyze platelet activation and the possible role of platelets in the amplification of the inflammatory response during Chikungunya infection. We prospectively included 132 patients attended at the Quinta D’Or hospital and 25 healthy volunteers during the 2016 epidemic in Rio de Janeiro, Brazil. We observed increased expression of CD62P on the surface of platelets, as well as increased plasma levels of CD62P and platelet-derived inflammatory mediators indicating that the Chikungunya infection leads to platelet activation. In addition, platelets from chikungunya patients exhibit increased expression of NLRP3, caspase 4, and cleaved IL-1β, suggestive of platelet-inflammasome engagement during chikungunya infection. In vitro experiments confirmed that the Chikungunya virus directly activates platelets. Moreover, we observed that platelet activation and soluble p-selectin at the onset of symptoms were associated with development of chronic forms of the disease. Collectively, our data suggest platelet involvement in the immune processes and inflammatory amplification triggered by the infection.
SEMA: Antigen B-cell conformational epitope prediction using deep transfer learning
Authors: Shashkova Tatiana I. , Umerenkov Dmitriy , Salnikov Mikhail , Strashnov Pavel V. , Konstantinova Alina V. , Lebed Ivan , Shcherbinin Dmitriy N. , Asatryan Marina N. , Kardymon Olga L. , Ivanisenko Nikita V.
Published: September 2022

One of the primary tasks in vaccine design and development of immunotherapeutic drugs is to predict conformational B-cell epitopes corresponding to primary antibody binding sites within the antigen tertiary structure. To date, multiple approaches have been developed to address this issue. However, for a wide range of antigens their accuracy is limited. In this paper, we applied the transfer learning approach using pretrained deep learning models to develop a model that predicts conformational B-cell epitopes based on the primary antigen sequence and tertiary structure. A pretrained protein language model, ESM-1v, and an inverse folding model, ESM-IF1, were fine-tuned to quantitatively predict antibody-antigen interaction features and distinguish between epitope and non-epitope residues. The resulting model called SEMA demonstrated the best performance on an independent test set with ROC AUC of 0.76 compared to peer-reviewed tools. We show that SEMA can quantitatively rank the immunodominant regions within the SARS-CoV-2 RBD domain. SEMA is available at https://github.com/AIRI-Institute/SEMAi and the web-interface http://sema.airi.net.
CyTOF analysis identifies unusual immune cells in urine of BCG-treated bladder cancer patients
Authors: Castellano Eva , Samba Célia , Esteso Gloria , Simpson Laura , Vendrame Elena , García‐Cuesta Eva M. , López‐Cobo Sheila , Álvarez-Maestro Mario , Linares Ana , Leibar Asier , Ranganath Thanmayi , Reyburn Hugh T. , Martínez‐Piñeiro Luis , Blish Catherine , Valés‐Gómez Mar
Published: September 2022

High grade non-muscle-invasive bladder tumours are treated with transurethral resection followed by recurrent intravesical instillations of Bacillus Calmette Guérin (BCG). Although most bladder cancer patients respond well to BCG, there is no clinical parameter predictive of treatment response, and when treatment fails, the prognosis is very poor. Further, a high percentage of NMIBC patients treated with BCG suffer unwanted effects that force them to stop treatment. Thus, early identification of patients in which BCG treatment will fail is really important. Here, to identify early stage non-invasive biomarkers of non-responder patients and patients at risk of abandoning the treatment, we longitudinally analysed the phenotype of cells released into the urine of bladder cancer patients 3-7 days after BCG instillations. Mass cytometry (CyTOF) analyses revealed a large proportion of granulocytes and monocytes, mostly expressing activation markers. A novel population of CD15+CD66b+CD14+CD16+ cells was highly abundant in several samples; expression of these markers was confirmed using flow cytometry and qPCR. A stronger inflammatory response was associated with increased cell numbers in the urine; this was not due to hematuria because the cell proportions were distinct from those in the blood. This pilot study represents the first CyTOF analysis of cells recruited to urine during BCG treatment, allowing identification of informative markers associated with treatment response for sub-selection of markers to confirm using conventional techniques. Further studies should jointly evaluate cells and soluble factors in urine in larger cohorts of patients to characterise the arms of the immune response activated in responders and to identify patients at risk of complications from BCG treatment.
Case report: Anti-NMDA receptor encephalitis manifesting as rapid weight loss and abnormal movement disorders with alternating unilateral ptosis and contralateral limb tremor
Authors: Han Yue , Gong Sizhu , Wan Yafei , Fu Xiyao , He Enling , Liu Min , Deng Fang
Published: September 2022

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, associated with immunoglobulin G (IgG) autoantibodies against the GluN1 subunit of the NMDAR, is one of the most common types of autoimmune encephalitis. In patients with anti-NMDAR encephalitis, movement disorders (MDs) are often frequent, mainly presenting as facial dyskinesias and stereotyped movements. The alternating clinical manifestation of limb tremor with unilateral ptosis is rare. Here, we report an interesting case of a 22-year-old woman with rapid weight loss presenting with staged dyskinesia. Interestingly, she typically showed persistent tremor of the right upper limb, which would stop when her left upper eyelid drooped uncontrollably, a phenomenon that lasted for a few seconds, followed by automatic upper eyelid lift and continued persistent tremor of the upper limb. Moreover, it was fortunate to find anti-NMDAR antibodies in her cerebrospinal fluid (CSF), which indicated the patient had anti-NMDAR encephalitis. And abnormal apparent diffusion coefficient (ADC) hyperintense signals on the left midbrain interpeduncular fossa explained this manifestation of focal neurological deficit. After the systematic administration of immunotherapy (intravenous immunoglobulin, IVIG), steroid pulse therapy, and symptomatic treatment, the initial symptoms were significantly relieved except for limb tremor. The MDs were becoming less visible for the next six months under topiramate prescriptions. Noteworthy, there are no specific MD phenotypes in anti-NMDAR encephalitis. We describe the young women with unique MDs and rapid weight loss to help us get a more comprehensive understanding of anti-NMDAR encephalitis.
Isolation of a cytolytic subpopulation of extracellular vesicles derived from NK cells containing NKG7 and cytolytic proteins
Authors: Aarsund Miriam , Nyman Tuula Anneli , Stensland Maria Ekman , Wu Yunjie , Inngjerdingen Marit
Published: September 2022

NK cells can broadly target and kill malignant cells via release of cytolytic proteins. NK cells also release extracellular vesicles (EVs) that contain cytolytic proteins, previously shown to induce apoptosis of a variety of cancer cells in vitro and in vivo. The EVs released by NK cells are likely very heterogeneous, as vesicles can be released from the plasma membrane or from different intracellular compartments. In this study, we undertook a fractionation scheme to enrich for cytolytic NK-EVs. NK-EVs were harvested from culture medium from the human NK-92 cell line or primary human NK cells grown in serum-free conditions. By combining ultracentrifugation with downstream density-gradient ultracentrifugation or size-exclusion chromatography, distinct EV populations were identified. Density-gradient ultracentrifugation led to separation of three subpopulations of EVs. The different EV isolates were characterized by label-free quantitative mass spectrometry and western blotting, and we found that one subpopulation was primarily enriched for plasma membrane proteins and tetraspanins CD37, CD82, and CD151, and likely represents microvesicles. The other major subpopulation was enriched in intracellularly derived markers with high expression of the endosomal tetraspanin CD63 and markers for intracellular organelles. The intracellularly derived EVs were highly enriched in cytolytic proteins, and possessed high apoptotic activity against HCT-116 colon cancer spheroids. To further enrich for cytolytic EVs, immunoaffinity pulldowns led to the isolation of a subset of EVs containing the cytolytic granule marker NKG7 and the majority of vesicular granzyme B content. We therefore propose that EVs containing cytolytic proteins may primarily be released via cytolytic granules.
Anticancer potential of Spirastrella pachyspira (marine sponge) against SK-BR-3 human breast cancer cell line and in silico analysis of its bioactive molecule sphingosine
Authors: Morais Shabna Roupal , K Chitra , Jeyabalan Srikanth , Wong Ling Shing , Sekar Mahendran , Chidambaram Kumarappan , Gan Siew Hua , Begum M. Yasmin , Izzati Mat Rani Nur Najihah , Subramaniyan Vetriselvan , Fuloria Shivkanya , Fuloria Neeraj Kumar , Safi Sher Zaman , Sathasivam Kathiresan V. , Selvaraj Siddharthan , Sharma Vipin Kumar
Published: September 2022

The rate of breast cancer is rapidly increasing and discovering medications with therapeutic effects play a significant role in women’s health. Drugs derived from marine sponges have recently received FDA approval for the treatment of malignant tumors, including metastatic breast cancer. Spirastrella pachyspira (marine sponge) is mainly obtained from the western coastal region of India, and its anticancer potential has not been explored. Hence, the present study aimed to evaluate the anticancer potential of Spirastrella pachyspira extracts and its bioactive molecule sphingosine. The extracts were prepared using hexane, chloroform, ethyl acetate, and ethanol. The cytotoxic potential of the extracts were determined by an in-vitro MTT assay using SK-BR-3 cancer cell line. Subsequently, acute toxicity investigation was conducted in Swiss albino mice. Then, the anticancer effects of the extract was investigated in a xenograft model of SK-BR-3 caused breast cancer. DAPI staining was used to assess the extract’s ability to induce apoptosis. In addition, in-silico study was conducted on sphingosine with extracellular site of HER2. The ethyl acetate extract of Spirastrella pachyspira (IC50: 0.04 µg/ml) showed comparable anticancer effects with standard doxorubicin (IC50: 0.054 µg/ml). The LD50 of the extracts in acute toxicity testing was fund to be 2000 mg/kg b.wt. The survival index of mice in ethanol extract was 83.33%, whereas that of standard doxirubicin was 100%, indicating that ethyl acetate extract Spirastrella pachyspira has good antiproliferative/cytotoxic properties. The results were well comparable with standard doxorubicin. Further, the docking studies of sphingosine against HER2 demonstrated that the bioactive molecule engage with the extracellular region of HER2 and block the protein as also shown by standard trastuzumab. The findings of this research suggest that Spirastrella pachyspira and sphingosine may be potential candidate for the treatments of breast cancer, particularly for HER2 positive cells. Overall, the present results demonstrate that sphingosine looks like a promising molecule for the development of new drugs for the treatment of cancer. However, in order to carefully define the sphingosine risk-benefit ratio, future research should focus on evaluating in-vivo and clinical anticancer studies. This will involve balancing both their broad-spectrum effectiveness and their toxicity.
Photophysiological response of diatoms in surface sediments to light exposure: A laboratory experiment on a diatom community in sediments from the Chukchi Sea
Authors: Fukai Yuri , Matsuno Kohei , Fujiwara Amane , Suzuki Koji
Published: September 2022

Diatoms form dense blooms in the Pacific Arctic region from spring to summer, supporting the unique benthic-pelagic coupling ecosystems. Although the Arctic has a severe light-limited season from autumn to winter, diatoms can proliferate in spring when sufficient light becomes available for photosynthesis. One of the crucial strategies for diatoms to survive in unfavorable growing conditions is to form resting stages. Because of enhanced primary and export production in the Pacific Arctic shelves, many viable diatom resting stages can be detected in the surface sediments. However, little is known about the photophysiological response of viable diatom cells, including resting stages, in sediments to light availability. We conducted a laboratory experiment investigating the photophysiological capabilities of the diatom cells containing resting stages using surface sediments from the Chukchi Sea shelf. As a result, diatoms grew dramatically after light exposure, and Chaetoceros socialis complex highly contributed to the enhanced diatom abundance. Their photophysiological changes were also evident from the maximum quantum efficiency (Fv/Fm) of photochemistry in photosystem II, 13C-based photosynthetic-energy (PE) parameters, diadinoxanthin (DD)-diatoxanthin (DT) pool size, and the de-epoxidation state (DES) of DD. Even after the excess light exposure suppressed the photosynthetic activity in the microalgal cells, the diatoms recovered quickly, indicating the high photophysiological plasticity to dynamic light changes. Therefore, our results suggest that diatoms in surface sediments have a high seeding potential for blooms in the Pacific Arctic shelf region.
Hydration kinetics of oil well cement in the temperature range between 5 and 30°C
Authors: Sun Lijun , Pang Xueyu , Yan Haibing
Published: September 2022

Modeling the hydration kinetics of oil well cement as a function of temperature is critical for offshore cementing projects related to natural gas hydrates. During this study, the heat release of oil well cement hydration in the temperature range between 5 and 30°C was monitored by isothermal calorimetry. The influence of the source of cement, water-to-cement (w/c) ratio, and CaCl2on hydration kinetics was evaluated in great detail. Results indicated the temperature effect on cement hydration kinetics can be modeled by a scale factor derived from the apparent activation energy (Ea) of the cement reaction.Eashowed moderate dependence on the cement source and relatively little dependence on the w/c ratio and CaCl2addition. By combining with previous experimental data, a function correlatingEaand temperature in a wide temperature range (5–87°C) was obtained.