bluuebunny/crossref_metadata_2025_split huggingface dataset:
GCTOF-MS Combined LC-QTRAP-MS/MS Reveals Metabolic Difference Between Osteoarthritis and Osteoporotic Osteoarthritis and the Intervention Effect of Erxian Decoction
Authors: Ma Zhenyuan , Wei Yibao , Zhang Li , Shi Xiaoqing , Xing Runlin , Liao Taiyang , Yang Nan , Li Xiaochen , Jie Lishi , Wang Peimin 
Published: July 2022

PurposeOP and OA are chronic bone diseases with high incidence in the middle-aged and elderly populations. The latest research shows that the pathological environment of OP may be involved in the aggravation of the pathological process of OA, and the pathological state of OP plays an important role in the aggravation of OA pathology. EXD is a traditional Chinese medicine decoction that has been used to treat osteoporosis. Therefore, we further study whether OA will be aggravated in the OP environment and whether EXD can alleviate OA by intervening in the OP environment. The purpose of this study was to analyze the effect of OP on OA metabolites by using metabolomic methods and to explore the intervention mechanism of EXD on osteoporotic OA.MethodThirty-two SD rats were randomly divided into normal group, OA group, OP-OA group, and EXD group. EXD was administered by gavage. Histopathological evaluation of cartilage tissue was performed using Saffron fast green and HE staining. Western blot and qRT-PCR were used to detect the expression levels of chondrogenesis genes SOX9, COL2A1, and COMP in cartilage tissue. GC-TOFMS and LC-QTRAP-MS/MS metabolomics methods were used to analyze the changes of metabolites in serum samples of rats in each group.ResultThe slice results showed that the cartilage damage in the OP-OA group was more serious than that in the OA group, which was significantly relieved after EXD intervention, indicating that the cartilage damage in the OP-OA group was more severe than that in the OA group and further reduced the protein and gene expressions of cartilage markers SOX9, COL2A1, and COMP. Thirty-seven substances were identified, and gentiopicroside, emodin, quercetin, and diosmetin were analyzed as possible active components of EXD. EXD treatment significantly reduced cartilage damage and reversed the expression of these markers. Metabolomics showed that EXD attenuated cartilage destruction by modulating the expression of cystine, chenodeoxycholate, and D-Turanose, involving glycolysis/gluconeogenesis, pantothenate, and CoA biosynthesis metabolic pathways.ConclusionThe OP environment may promote the progression of OA through metabolic factors. The benign intervention of EXD in osteoporotic OA involves cystine, chenodeoxycholate, and D-Turanose, and their associated glycolysis/gluconeogenesis, pantothenate, and CoA biosynthesis metabolic pathways. Therefore, we have a deep understanding of the metabolic-related intervention of EXD in osteoporotic OA and are eager to better understand the mechanism of multi-targeted intervention of EXD in bone metabolic lesions.
Mutational Profile and Potential Molecular Therapeutic Targets of Pheochromocytoma
Authors: Ma Xiaosen , Ling Chao , Zhao Meng , Wang Fen , Cui Yunying , Wen Jin , Ji Zhigang , Zhang Caili , Chen Shi , Tong Anli , Li Yuxiu 
Published: July 2022

PurposePheochromocytoma/paraganglioma (PCC/PGL; collectively known as PPGL) can be driven by germline and somatic mutations in susceptibility genes. We aimed to investigate the mutation profile and clinical features of pathogenic genes in highly genetically heterogeneous PPGL and to preliminary explore molecular therapeutic targets in PPGL.MethodsWe established a panel of 260 genes, including susceptibility genes of PPGL and other important tumorigenic genes to sequence 107 PPGL tissues.ResultsOverall, 608 genomic mutations were identified in 107 PPGL tissues. Almost 57% of PPGL tissue samples exhibited pathogenic mutations, and the most frequently mutated gene was SDHB (15/107, 14%). SDHB and HRAS were the most commonly mutated genes in germline-mutated PPGL (25/107, 23%) and nongermline-mutated PPGL (36/107, 34%), respectively. In addition, novel pathogenic mutations were detected in sporadic PPGL. PPGL with mutations in the hypoxia pathway had an earlier onset and higher norepinephrine level than those in the kinase pathway. Receptor tyrosine kinase (RTK; 22%, 24/107), mitogen-activated protein kinase (MAPK; 14%, 15/107), and tyrosine kinase (TK; 2%, 2/107) pathways were the most frequently mutated pathways in PPGL.ConclusionOur results provided the genetic mutation profile in PPGL tissues. Genetic mutations in PPGL were mainly concentrated in the RTK, TK, and MAPK pathways, suggesting potential molecular therapeutic targets for PPGL.
Altered expression of Tim family molecules and an imbalanced ratio of Tim-3 to Tim-1 expression in patients with type 1 diabetes
Authors: Liu Yikai , Chen Zhiying , Xiao Yang , Chen Hongzhi , Zhou Zhiguang 
Published: July 2022

BackgroundT-cell immunoglobulin and mucin domain (Tim) proteins are immunomodulatory molecules that play key roles in the regulation of T-cell activation. Published studies have reported that Tim molecules are involved in the pathogenesis of certain autoimmune diseases. Type 1 diabetes (T1D) is an autoimmune disease in which T cells mediate the destruction of islet β cells. However, the expression of Tim molecules in T1D remains unclear. In this study, we measured the expression of Tim family molecules as well as T-cell subset-specific transcription factors in T1D patients, and we explored the possible involvement of Tim molecules in the pathogenesis of T1D.MethodsNinety T1D patients, Thirty-six type 2 diabetes (T2D) patients and forty healthy controls (HCs) were recruited for this study. Peripheral blood mononuclear cells (PBMCs) were isolated, RNA was extracted from the PBMCs and reverse transcribed into cDNA, and gene expression patterns were analysed by RT–qPCR. The expression of Tim molecules in different T-cell subsets was analysed by flow cytometry.ResultsCompared with that in HCs, the mRNA expression of Tim-1 and RORC was increased in T1D patients (P=0.0355 and P=0.0423, respectively), while the expression of Tim-3 was decreased (P=0.0013). In addition, compared with HCs, the ratio of Tim-3 to Tim-1 expression in diabetic patients was decreased (P&lt;0.0001 for T1D and P=0.0387 for T2D). The ratios of T-Bet to GATA3 expression and RORC to FOXP3 expression were higher in T1D patients than in HCs (P=0.0042 and P=0.0066, respectively). Furthermore, the T1D patients with defective islet function had more significant imbalances in the Tim-3/Tim-1 and RORC/FOXP3 ratios (P&lt;0.0001, and P=0.001, respectively). Moreover, Both Tim-3 expression in CD4+ T cells and the Tim-3 to Tim-1 ratio were elevated in T1D in the remission phase compared to T1D.ConclusionOur study revealed altered expression of Tim molecules in T1D patients. The imbalanced ratios of Tim-3/Tim-1 expression were more pronounced in T1D patients with defective islet function. However, alterations in Tim molecule expression are mitigated in T1D in the remission phase. All these findings suggest that Tim family molecules may be involved in the pathogenesis of T1D.
Analysis of immunization time, amplitude, and adverse events of seven different vaccines against SARS-CoV-2 across four different countries
Authors: Romero-Ibarguengoitia Maria Elena , González-Cantú Arnulfo , Pozzi Chiara , Levi Riccardo , Mollura Maximiliano , Sarti Riccardo , Sanz-Sánchez Miguel Ángel , Rivera-Salinas Diego , Hernández-Ruíz Yodira Guadalupe , Armendariz-Vázquez Ana Gabriela , Del Rio-Parra Gerardo Francisco , Barco-Flores Irene Antonieta , González-Facio Rosalinda , Azzolini Elena , Barbieri Riccardo , de Azevedo Dias Alessandro Rodrigo , Henriques Guimarães Júnior Milton , Bastos-Borges Alessandra , Acciardi Cecilia , Paez-Bo Graciela , Teixeira Mauro Martins , Rescigno Maria 
Published: July 2022

BackgroundScarce information exists in relation to the comparison of seroconversion and adverse events following immunization (AEFI) with different SARS-CoV-2 vaccines. Our aim was to correlate the magnitude of the antibody response to vaccination with previous clinical conditions and AEFI.MethodsA multicentric comparative study where SARS-CoV-2 spike 1-2 IgG antibodies IgG titers were measured at baseline, 21-28 days after the first and second dose (when applicable) of the following vaccines: BNT162b2 mRNA, mRNA-1273, Gam-COVID-Vac, Coronavac, ChAdOx1-S, Ad5-nCoV and Ad26.COV2. Mixed model and Poisson generalized linear models were performed.ResultsWe recruited 1867 individuals [52 (SD 16.8) years old, 52% men]. All vaccines enhanced anti-S1 and anti-S2 IgG antibodies over time (p&lt;0.01). The highest increase after the first and second dose was observed in mRNA-1273 (p&lt;0.001). There was an effect of previous SARS-CoV-2 infection; and an interaction of age with previous SARS-CoV-2 infection, Gam-COVID-Vac and ChAdOx1-S (p&lt;0.01). There was a negative correlation of Severe or Systemic AEFI (AEs) of naïve SARS-CoV-2 subjects with age and sex (p&lt;0.001); a positive interaction between the delta of antibodies with Gam-COVID-Vac (p=0.002). Coronavac, Gam-COVID-Vac and ChAdOx1-S had less AEs compared to BNT162b (p&lt;0.01). mRNA-1273 had the highest number of AEFIs. The delta of the antibodies showed an association with AEFIs in previously infected individuals (p&lt;0.001).ConclusionsThe magnitude of seroconversion is predicted by age, vaccine type and SARS-CoV-2 exposure. AEs are correlated with age, sex, and vaccine type. The delta of the antibody response only correlates with AEs in patients previously exposed to SARS-CoV-2.Registration numberClinicalTrials.gov, identifier NCT05228912.
MALT1 regulates Th2 and Th17 differentiation via NF-κB and JNK pathways, as well as correlates with disease activity and treatment outcome in rheumatoid arthritis
Authors: Wang Qiubo , Wang Yapeng , Liu Qingyang , Chu Ying , Mi Rui , Jiang Fengying , Zhao Jingjing , Hu Kelong , Luo Ran , Feng Yufeng , Lee Harrison , Zhou Dong , Mi Jingyi , Deng Ruoyu 
Published: July 2022

ObjectiveMALT1 regulates immunity and inflammation in multiple ways, while its role in rheumatoid arthritis (RA) is obscure. This study aimed to investigate the relationship of MALT1 with disease features, treatment outcome, as well as its effect on Th1/2/17 cell differentiation and underlying molecule mechanism in RA.MethodsTotally 147 RA patients were enrolled. Then their blood Th1, Th2, and Th17 cells were detected by flow cytometry. Besides, PBMC MALT1 expression was detected before treatment (baseline), at week (W) 6, W12, and W24. PBMC MALT1 in 30 osteoarthritis patients and 30 health controls were also detected. Then, blood CD4+ T cells were isolated from RA patients, followed by MALT1 overexpression or knockdown lentivirus transfection and Th1/2/17 polarization assay. In addition, IMD 0354 (NF-κB antagonist) and SP600125 (JNK antagonist) were also added to treat CD4+ T cells.ResultsMALT1 was increased in RA patients compared to osteoarthritis patients and healthy controls. Meanwhile, MALT1 positively related to CRP, ESR, DAS28 score, Th17 cells, negatively linked with Th2 cells, but did not link with other features or Th1 cells in RA patients. Notably, MALT1 decreased longitudinally during treatment, whose decrement correlated with RA treatment outcome (treatment response, low disease activity, or disease remission). In addition, MALT1 overexpression promoted Th17 differentiation, inhibited Th2 differentiation, less affected Th1 differentiation, activated NF-κB and JNK pathways in RA CD4+ T cells; while MALT1 knockdown exhibited the opposite effect. Besides, IMD 0354 and SP600125 addition attenuated MALT1’s effect on Th2 and Th17 differentiation.ConclusionMALT1 regulates Th2 and Th17 differentiation via NF-κB and JNK pathways, as well as correlates with disease activity and treatment outcome in RA.
A Cross-Tissue Transcriptome-Wide Association Study Identifies Novel Susceptibility Genes for Juvenile Idiopathic Arthritis in Asia and Europe
Authors: Xu Jiawen , Ma Jun , Zeng Yi , Si Haibo , Wu Yuangang , Zhang Shaoyun , Shen Bin 
Published: July 2022

BackgroundJuvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children, and its pathogenesis is still unclear. Genome-wide association studies (GWASs) of JIA have identified hundreds of risk factors, but few of them implicated specific biological mechanisms.MethodsA cross-tissue transcriptome-wide association study (TWAS) was performed with the functional summary-based imputation software (FUSION) tool based on GWAS summary datasets (898 JIA patients and 346,102 controls from BioBank Japan (BBJ)/FinnGen). The gene expression reference weights of skeletal muscle and the whole blood were obtained from the Genotype-Tissue Expression (GTExv8) project. JIA-related genes identified by TWAS findings genes were further compared with the differentially expressed genes (DEGs) identified by the mRNA expression profile of JIA from the Gene Expression Omnibus (GEO) database (accession number: GSE1402). Last, candidate genes were analyzed using functional enrichment and annotation analysis by Metascape to examine JIA-related gene sets.ResultsThe TWAS identified 535 significant genes with P &lt; 0.05 and contains 350 for Asian and 195 for European (including 10 genes both expressed in Asian and European), such as CDC16 (P = 1.72E-03) and PSMD5-AS1 (P = 3.65E-02). Eight overlapping genes were identified based on TWAS results and DEGs of JIA patients, such as SIRPB1 (PTWAS = 4.21E-03, PDEG = 1.50E-04) and FRAT2 (PTWAS = 2.82E-02, PDEG = 1.43E-02). Pathway enrichment analysis of TWAS identified 183 pathways such as cytokine signaling in the immune system and cell adhesion molecules. By integrating the results of DEGs pathway and process enrichment analyses, 19 terms were identified such as positive regulation of T-cell activation.ConclusionBy conducting two populations TWAS, we identified a group of JIA-associated genes and pathways, which may provide novel clues to uncover the pathogenesis of JIA.
Knowledge mapping and research hotspots of immunotherapy in renal cell carcinoma: A text-mining study from 2002 to 2021
Authors: Liu Kun , Zhao Seling , Li Jian , Zheng Yikun , Wu Haiyang , Kong Jianqiu , Shen Zefeng 
Published: July 2022

BackgroundRenal cell carcinoma (RCC) is one of the most lethal urological malignancies, and because early-stage RCC is asymptomatic, many patients present metastatic diseases at first diagnosis. With the development of immunotherapy, the treatment of RCC has entered a new stage and has made a series of progress. This study mainly outlines the knowledge map and detects the potential research hotspots by using bibliometric analysis.MethodsPublications concerning RCC immunotherapy from 2002 to 2021 in the Web of Science Core Collection were collected. Visualization and statistical analysis were mainly performed by freeware tools VOSviewer, CiteSpace, R software, and Microsoft Office Excel 2019.ResultsA total of 3,432 papers were collected in this study, and the annual number of papers and citations showed a steady growth trend. The United States is the leading country with the most high-quality publications and is also the country with the most international cooperation. The University of Texas MD Anderson Cancer Center is the most productive organization. The Journal of Clinical Oncology is the highest co-cited journal, and Brian I. Rini is both the most prolific author and the author with the largest centrality. The current research hotspots may be focused on “immune checkpoint inhibitors (ICIs),” “PD-1,” and “mammalian target of rapamycin.”ConclusionImmunotherapy has a bright future in the field of RCC treatment, among which ICIs are one of the most important research hotspots. The main future research directions of ICI-based immunotherapy may focus on combination therapy, ICI monotherapy, and the development of new predictive biomarkers.
Chasing the offshore wind farm wind-wake-induced upwelling/downwelling dipole
Authors: Floeter Jens , Pohlmann Thomas , Harmer André , Möllmann Christian 
Published: July 2022

The operational principle of offshore wind farms (OWF) is to extract kinetic energy from the atmosphere and convert it into electricity. Consequently, a region of reduced wind speed in the shadow zone of an OWF, the so-called wind-wake, is generated. As there is a horizontal wind speed deficit between the wind-wake and the undisturbed neighboring regions, the locally reduced surface stress results in an adjusted Ekman transport. Subsequently, the creation of a dipole pattern in sea surface elevation induces corresponding anomalies in the vertical water velocities. The dynamics of these OWF wind-wake induced upwelling/downwelling dipoles have been analyzed in earlier model studies, and strong impacts on stratified pelagic ecosystems have been predicted. Here we provide for the first time empirical evidence of the existence of such upwelling/downwelling dipoles. The data were obtained by towing a remotely operated vehicle (TRIAXUS ROTV) through leeward regions of operational OWFs in the summer stratified North Sea. The undulating TRIAXUS transects provided high-resolution CTD data which enabled the characterization of three different phases of the ephemeral life cycle of a wind-wake-induced upwelling/downwelling dipole: development, operation, and erosion. We identified two characteristic hydrographic signatures of OWF-induced dipoles: distinct changes in mixed layer depth and potential energy anomaly over a distance &lt; 5 km and a diagonal excursion of the thermocline of ~10–14 m over a dipole dimension of ~10–12 km. Whether these anthropogenically induced abrupt changes are significantly different from the corridor of natural variability awaits further investigations.
A global atlas of potential thermal refugia for coral reefs generated by internal gravity waves
Authors: Bachman Scott D. , Kleypas Joan A. , Erdmann Mark , Setyawan Edy 
Published: July 2022

Coral reefs are highly threatened by ocean warming and the majority are likely to be lost in less than three decades. A first step in maximizing reef conservation through this period is to identify where coral reefs are more likely to survive rising ocean temperatures, such as locations that experience lower temperatures than surrounding regions, high temperature variability, and high food supply. Such conditions are often the result of naturally occurring internal gravity waves (IGWs), oscillatory subsurface disturbances that can entrain cooler and/or nutrient-rich subsurface waters and cause high frequency temperature fluctuations. These features usually remain undetected because they occur subsurface and at spatial scales of O(1 km) and smaller. To shed light on where IGWs are likely to impact temperature conditions within coral reef regions, we present an analysis of data from the LLC4320, a massive high resolution (1/48˚; &lt; 2.5 km) numerical global ocean simulation. The results highlight strong regional differences in the incidence of IGW-induced temperature variability. The analysis also reveals that thermal refugia are limited to depths where high temperature variability coincides with the actual reef depth and may not persist year-round. Assuming 10-m depth as the nominal reef depth, reef regions likely to benefit from IGW-induced cooling occur in SE Asia and the Coral Triangle, the Galápagos, along the Pacific shelf of Central America, and isolated locations worldwide. Such refugia are rare within the Atlantic reef sector. An interactive global atlas showing the results of this study has been made freely available online at https://ncar.github.io/coral-viz/.
Applications of social theories of learning in health professions education programs: A scoping review
Authors: Mukhalalati Banan , Elshami Sara , Eljaam Myriam , Hussain Farhat Naz , Bishawi Abdel Hakim 
Published: July 2022

IntroductionIn health professions education (HPE), acknowledging and understanding the theories behind the learning process is important in optimizing learning environments, enhancing efficiency, and harmonizing the education system. Hence, it is argued that learning theories should influence educational curricula, interventions planning, implementation, and evaluation in health professions education programs (HPEPs). However, learning theories are not regularly and consistently implemented in educational practices, partly due to a paucity of specific in-context examples to help educators consider the relevance of the theories to their teaching setting. This scoping review attempts to provide an overview of the use of social theories of learning (SToLs) in HPEPs.MethodA scoping search strategy was designed to identify the relevant articles using two key concepts: SToLs, and HPEPs. Four databases (PubMed, ERIC, ProQuest, and Cochrane) were searched for primary research studies published in English from 2011 to 2020. No study design restrictions were applied. Data analysis involved a descriptive qualitative and quantitative summary according to the SToL identified, context of use, and included discipline.ResultsNine studies met the inclusion criteria and were included in the analysis. Only two SToLs were identified in this review: Bandura's social learning theory (n = 5) and Lave and Wenger's communities of practice (CoP) theory (n = 4). A total of five studies used SToLs in nursing programs, one in medicine, one in pharmacy, and two used SToLs in multi-disciplinary programs. SToLs were predominantly used in teaching and learning (n = 7), with the remaining focusing on assessment (n = 1) and curriculum design (n = 1).ConclusionsThis review illustrated the successful and effective use of SToLs in different HPEPs, which can be used as a guide for educators and researchers on the application of SToLs in other HPEPs. However, the limited number of HPEPs that apply and report the use of SToLs suggests a potential disconnect between SToLs and educational practices. Therefore, this review supports earlier calls for collaborative reform initiatives to enhance the optimal use of SToLs in HPEPs. Future research should focus on the applicability and usefulness of other theories of learning in HPEPs and on measuring implementation outcomes.Systematic Review Registration:https://www.researchregistry.com/browse-the-registry#registryofsystematicreviewsmetaanalyses/registryofsystematicreviewsmeta-analysesdetails/60070249970590001bd06f38/, identifier review registry1069.
Cytoplasmic strings between ICM and mTE are a positive predictor of clinical pregnancy and live birth outcomes: A time-lapse study
Authors: Ma Bing-Xin , Yang Liu , Tian Yu , Jin Lei , Huang Bo 
Published: July 2022

BackgroundElective single blastocyst transfer (eSBT) is considered to reduce the incidence of multiple pregnancy compared to double embryo transfer. Blastocyst selection is the key to achieving pregnancy. In the past, morphological assessment was the main criterion used to select blastocyst. Some important morphological parameters are considered to be clinically valuable, such as cytoplasmic strings traversing from the inner cell mass (ICM) and mural trophectoderm (mTE).MethodsIn this study, 1,267 elective frozen-thawed eSBT cycles cultured in a time-lapse culture system from January 2018 to May 2019 were included. Blastocysts were grouped into “present” and “absent” according to the appearance of cytoplasmic strings between ICM and mTE cells. The “present” group was further categorized according to the quantity of cytoplasmic strings between the ICM and mTE cells.ResultsA time-lapse analysis indicated that cytoplasmic strings between ICM and mTE were more visible among good quality blastocysts. Furthermore, blastocysts with cytoplasmic strings showed higher clinical pregnancy and live birth rates (P = 0.011 and 0.003), while no significant differences were observed in abortion rate and birth weight (P = 0.466 and 0.556).ConclusionsIn conclusion, although the results of previous studies about cytoplasmic strings have been controversial, the present time-lapse analysis provides evidence for the first time that cytoplasmic strings between ICM and mTE cells are a positive predictor of clinical pregnancy and live birth outcomes in elective frozen-thawed single blastocyst transfer cycles.