bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Multiple Injection Strategies on Heavy-Duty Diesel Energy Distributions and Emissions Under High Peak Combustion Pressures
Authors: Zhang Zhao , Liu Haifeng , Yue Zongyu , Wu Yangyi , Kong Xiangen , Zheng Zunqing , Yao Mingfa 
Published: April 2022

Peak combustion pressures (PCP) are increased in heavy-duty diesel engines to obtain higher thermal efficiency. Fuel injection strategy has been a major measure to improve the combustion and emissions of diesel engines. But most existing work of multi-injection strategies was not limited by PCP or was conducted under lower PCP (∼15 MPa). In this study, an experimental study is conducted to further improve the understanding of injection strategies on engine performance under a relative higher peak combustion pressure at 20 MPa. The four tested injection strategies are single main injection, pilot-main injection, main-post injection, and pilot-main-post injection. The effects of PCP on brake thermal efficiency (BTE) and other engine performances are also investigated under the same NOx emissions conditions. Results indicate that more advanced injection timing can obtain higher BTE, while the injection pressure has less effects on BTE as it is higher than 120 MPa. For double-injection, the smaller interval on pilot-main or main-post and the less pilot or post mass improves BTE and emissions. The PCPs are linearly correlated to the BTE, peak average temperature, and peak pressure rise rate (PRR), and the increment of BTE, peak average temperature, and peak PRR are about 0.3%, 30 K, and 0.1 MPa/CA for every 1 MPa increase in PCP, respectively. This also means that the improvement on BTE by the increase of PCP imparts greater thermal and mechanical loads on engine materials and components. At 20 MPa PCP, based on the optimized injection strategies, the BTE of all four strategies is about 42.8%, and the peak PRR of all four strategies is about 0.8 MPa/CA. At a given NOx emission of 17.4 g/kWh and approximate 20 MPa PCP, all four injection strategies have minor effects on distribution of fuel energy and emissions. Therefore, it can be concluded that the injection strategies have fewer effects on BTE and emissions at the higher peak combustion pressure of 20 MPa; the main purpose of injection strategies is to reduce the peak PRR or reach the potentially required temperature for aftertreatment devices.
Investigation of Chromosomal Structural Abnormalities in Patients With Undiagnosed Neurodevelopmental Disorders
Authors: Cao Ye , Luk Ho Ming , Zhang Yanyan , Chau Matthew Hoi Kin , Xue Shuwen , Cheng Shirley S. W. , Li Albert Martin , Chong Josephine S. C. , Leung Tak Yeung , Dong Zirui , Choy Kwong Wai , Lo Ivan Fai Man 
Published: April 2022

Background: Structural variations (SVs) are various types of the genomic rearrangements encompassing at least 50 nucleotides. These include unbalanced gains or losses of DNA segments (copy number changes, CNVs), balanced rearrangements (such as inversion or translocations), and complex combinations of several distinct rearrangements. SVs are known to play a significant role in contributing to human genomic disorders by disrupting the protein-coding genes or the interaction(s) with cis-regulatory elements. Recently, different types of genome sequencing-based tests have been introduced in detecting various types of SVs other than CNVs and regions with absence of heterozygosity (AOH) with clinical significance.Method: In this study, we applied the mate-pair low pass (∼4X) genome sequencing with large DNA-insert (∼5 kb) in a cohort of 100 patients with neurodevelopmental disorders who did not receive informative results from a routine CNV investigation. Read-depth-based CNV analysis and chimeric-read-pairs analysis were used for CNV and SV analyses. The region of AOH was indicated by a simultaneous decrease in the rate of heterozygous SNVs and increase in the rate of homozygous SNVs.Results: First, we reexamined the 25 previously reported CNVs among 24 cases in this cohort. The boundaries of these twenty-five CNVs including 15 duplications and 10 deletions detected were consistent with the ones indicated by the chimeric-read-pairs analysis, while the location and orientation were determined in 80% of duplications (12/15). Particularly, one duplication was involved in complex rearrangements. In addition, among all the 100 cases, 10% of them were detected with rare or complex SVs (&gt;10 Kb), and 3% were with multiple AOH (≥5 Mb) locating in imprinting chromosomes identified. In particular, one patient with an overall value of 214.5 Mb of AOH identified on 13 autosomal chromosomes suspected parental consanguinity.Conclusion: In this study, mate-pair low-pass GS resolved a significant proportion of CNVs with inconclusive significance, and detected additional SVs and regions of AOH in patients with undiagnostic neurodevelopmental disorders. This approach complements the first-tier CNV analysis for NDDs, not only by increasing the resolution of CNV detection but also by enhancing the characterization of SVs and the discovery of potential causative regions (or genes) contributory to could be complex in composition NDDs.
Cell-Free DNA Promotes Inflammation in Patients With Oral Lichen Planus via the STING Pathway
Authors: Deng Jing , Pan Weiyi , Ji Ning , Liu Na , Chen Qian , Chen Jinhuan , Sun Yutong , Xie Liang , Chen Qianming 
Published: April 2022

BackgroundDamaged and dead cells release cell-free DNA (cfDNA) that activates cyclic GMP–AMP (cGAMP) synthase (cGAS), which leads to the activation of stimulator of interferon genes (STING) via the second messenger cGAMP. STING promotes the production of inflammatory cytokines and type I interferons to induce an inflammatory response. Oral lichen planus (OLP), a chronic autoimmune disease involving oral mucosa characterized by the apoptosis of keratinocytes mediated by T-lymphocytes, is related to the activation of multiple inflammatory signaling pathways. Currently, the relationship between cfDNA and OLP has not been confirmed. We hypothesized that cfDNA may be a potential therapeutic target for OLP.MethodscfDNA was extracted from the saliva and plasma of OLP patients; its concentration was measured using the Quanti-iT-PicoGree kit and its relationship with OLP inflammation was assessed. cfDNA of OLP patients (cfDNA-OLP) was transfected into THP-1 macrophages and the expression of inflammatory factors was investigated by performing quantitative real time PCR (qRT-PCR), western blotting, and enzyme-linked immunosorbent assay (ELISA). STING expression was analyzed in the tissues of OLP patients and healthy controls using immunohistochemical staining and western blotting. siRNA was used to knockdown STING expression in THP-1 macrophages, and the inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) secreted by cells following cfDNA-OLP transfection were detected using ELISA. Finally, the effect of the cationic polymer PAMAM-G3 was evaluated on the treatment of inflammation induced by cfDNA-OLP.ResultsThe concentration of cfDNA in the saliva and plasma of OLP patients was considerably higher than that of healthy controls, and it positively correlated with the levels of inflammatory cytokines and clinical characteristics. cfDNA-OLP induced an inflammatory response in THP-1 macrophages. STING expression was significantly higher in OLP tissues than in the gingival tissues of healthy controls. STING knockdown suppressed cfDNA-OLP-induced inflammation in THP-1 macrophages. PAMAM-G3 inhibited the inflammatory response caused by cfDNA-OLP.ConclusionThe cfDNA level is increased in OLP patients, and the STING pathway activated by cfDNA-OLP might play a critical role in OLP pathogenesis. Treatment with PAMAM-G3 reduced the inflammation induced by cfDNA-OLP, and therefore, may be a potential treatment strategy for OLP.
Clinical and Renal Histology Findings and Different Responses to Induction Treatment Affecting the Long-Term Renal Outcomes of Children With ANCA-Associated Vasculitis: a Single-Center Cohort Analysis
Authors: Yang Jing , Yang Yuan , Xu Yongli , Zhou Lanqi , Zhou Luowen , Yin Xiaoling , Pu Jinyun , Yang Fengjie , Liu Yaping , He Yonghua , Chen Yaxian , Yuan Huiqing , Qiu Liru , Zhang Yu , Chen Yu , Liu Tonglin , Tang Jinhui , Zhou Jianhua 
Published: April 2022

IntroductionAntineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is relatively rare in children. This article aimed to analyze clinical and renal histology findings and different responses to induction treatment associated with the long-term renal outcomes in children with AAV in a single center.MethodsAll pediatric patients with AAV admitted to Tongji Hospital from January 2002 to January 2021 were included in the study. The demographic, clinical, pathological, laboratory, and treatment data and outcomes were collected and analyzed to identify predictors associated with response to induction treatment and progression to end-stage renal disease (ESRD).ResultsIn total, 48 children with AAV were included in this cohort; 81.25% of them were women, and 91.7% were microscopic polyangiitis (MPA). Kidney involvement was found in 45 patients (93.75%). The most common histopathological subtype was crescentic form in this cohort according to Berden’s classification. In total, 34 patients (70.8%) showed eGFR &lt;60 ml/min/1.73 m2 at the time of diagnosis. Complete and partial remission was achieved in 8 patients (16.7%) and 19 patients (39.6%), respectively, following 6-month induction treatment. Half of the patients eventually progressed to ESRD at a mean time of (13.04 ± 15.83) months after diagnosis. The independent predictors of nonremission following induction treatment and progression to ESRD were baseline eGFR &lt;60 ml/min/1.73 m2 and hypertension at diagnosis. Renal survival significantly decreased over time in patients with renal sclerotic subtypes or those with nonremission following induction treatment by Kaplan–Meier curve estimation.ConclusionsOur study demonstrates that women, MPA, and crescentic subtypes are predominant in pediatric AAV in China. Initial renal failure (eGFR &lt;60 ml/min/1.73 m2), hypertension, sclerotic pathological subtype, and nonremission following induction treatment are predictive of long-term renal outcomes.
Elevated Expression of TLR2 in Aging Hearts Exacerbates Cardiac Inflammatory Response and Adverse Remodeling Following Ischemia and Reperfusion Injury
Authors: Zhai Yufeng , Ao Lihua , Yao Qingzhou , The Erlinda , Fullerton David A. , Meng Xianzhong 
Published: April 2022

This study tested the hypothesis that Toll-like receptor 2 (TLR2) augments the inflammatory responses and adverse remodeling in aging hearts to exacerbate myocardial injury and cardiac dysfunction.MethodsOld (20-22 months old) and adult (4-6 months old) mice of C57BL/6 wild-type and TLR2 knockout (KO) were subjected to coronary artery ligation (30 minutes) and reperfusion (3 or 14 days). Left ventricle function was assessed using a pressure-volume microcatheter. Cardiac infarct size was determined by histology. Levels of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), matrix metalloproteinase 9 (MMP 9), and collagen I in non-ischemic myocardium were assessed by immunoblotting. Monocyte chemoattractant protein-1 (MCP-1), keratinocyte chemoattractant (KC), and interleukin-6 (IL-6) levels in ischemic and non-ischemic myocardium were measured by enzyme-linked immunosorbent assay (ELISA). TLR2 expression in the myocardium of untreated wild type mice was also measured by immunoblotting.ResultsHigher levels of MCP-1, KC, IL-6 were induced in both ischemic and non-ischemic myocardium of old wild type mice at day 3 and 14 following ischemia/reperfusion (I/R) than those of adult wild type mice. The hyper-inflammatory responses to I/R in aging hearts were associated with elevated levels of myocardial TLR2. TLR2 KO markedly down-regulated the expression of MCP-1, KC, IL-6, ICAM-1 and VCAM-1 in aging hearts at day 3 and 14 following I/R. The down-regulated inflammatory activity in aging TLR2 KO hearts was associated with attenuated production of MMP 9 and collagen I at day 14 and resulted in reduced infarct size and improved cardiac function.ConclusionElevated expression of myocardial TLR2 contributes to the mechanism by which aging exacerbates the inflammatory responses, adverse remodeling and cardiac dysfunction following myocardial I/R in aging.
The Protective Effects of Inulin-Type Fructans Against High-Fat/Sucrose Diet-Induced Gestational Diabetes Mice in Association With Gut Microbiota Regulation
Authors: Miao Miao , Wang Qing , Wang Xinyan , Fan Chong , Luan Ting , Yan Lina , Zhang Yue , Zeng Xin , Dai Yongmei , Li Ping 
Published: April 2022

BackgroundInulin-type fructans (ITF) have been used as prebiotics to alleviate glucose and lipid metabolism disorders. However, few studies evaluated the microbial mechanism of ITF in improving maternal metabolic status during pregnancy.MethodsC57BL/6J mice were fed a high-fat/sucrose diet (HFD) for 4 weeks before and throughout pregnancy to induce a model of gestational diabetes mellitus (GDM). Body weight, glycolipid metabolic parameters, and fecal short-chain fatty acids (SCFAs) were assessed in the experimental process. The effects of ITF on the fecal microbiota were analyzed by 16S rRNA gene amplicon sequencing.ResultsPregnant HFD-fed mice displayed significant insulin resistance and dyslipidemia. ITF (3.33 g/kg/day) treatment improved glucose and lipid metabolism disorder parameters in HFD-induced GDM mice and alleviated fat accumulation and glucose intolerance. The alpha diversity of the gut microbial community was increased in ITF mice, while the beta diversity returned to the level of normal chow diet (NCD) mice. Interestingly, Verrucomicrobia, Bifidobacterium, and Akkermansia were obviously enriched, while Dubosiella was obviously lessened after inulin treatment. Further analysis indicated that Dubosiella was positively correlated with markers of glycolipid metabolism disorders, whereas the ITF-supplemented diet partially reversed the changes.ConclusionOur results suggest that the ITF treatment may alleviate glucose and lipid metabolism disorders with the mediation of gut microbiota.
Alterations and Correlations of Gut Microbiota and Fecal Metabolome Characteristics in Experimental Periodontitis Rats
Authors: Wu Lan , Han Jie , Nie Jia-Yan , Deng Tong , Li Cheng , Fang Cheng , Xie Wen-Zhong , Wang Shuang-Ying , Zeng Xian-Tao 
Published: April 2022

ObjectivesPeriodontitis affects the progression of many diseases, while its detailed mechanism remains unclear. This study hopes to provide new ideas for exploring its mechanism by analyzing the gut microbiota and fecal metabolic characteristics of experimental periodontitis rats.MethodsA total of 10 rats were randomly divided into ligature-induced experimental periodontitis (EP) group and healthy control group. After 4 weeks of the experiment, the feces of all rats were collected for sequencing through 16S ribosomal DNA (rDNA) sequencing technology and liquid chromatography–mass spectrometry (LC–MS).Results16S rDNA sequencing results showed that the β-diversity of gut microbiota was significantly different between the EP and control group, and the levels of dominant genera were different. Compared with the control group, Ruminococcus, Escherichia, and Roseburia were significantly enriched in EP, and Coprococcus, Turicibacter, Lachnospira were significantly decreased. Correlation analysis showed that Roseburia exhibited the highest correlation within the genus. Of 3,488 qualitative metabolites, 164 metabolites were upregulated and 362 metabolites were downregulated in EP. Enrichment analysis showed that periodontitis significantly changed 45 positive/negative ion metabolic pathways. Five KEGG pathways, protein digestion and absorption, tyrosine metabolism, glycolysis/gluconeogenesis, niacin and nicotinamide metabolism, and oxidative phosphorylation, are enriched in both the microbiome and metabolome. Correlation analysis showed that the genera with significant differences in periodontitis were usually significantly correlated with more metabolites, such as Roseburia, Lachnospira, Escherichia, Turicibacter, and Ruminococcus. The genera with the same changing trend tended to have a similar correlation with some certain metabolites. In addition, vitamin D2 and protoporphyrin IX have the most significant correlations with microorganisms.ConclusionOur study reveals that periodontitis alters gut microbiota and fecal metabolites. The correlation analysis of microbiota and metabolome provides a deeper understanding of periodontitis, and also provides a direction for the study of periodontitis affecting other diseases.
A Qualitative Signature to Identify TERT Promoter Mutant High-Risk Tumors in Low-Grade Gliomas
Authors: Zheng Weicheng , Zhang Ruolan , Huang Ziru , Li Jianpeng , Wu Haonan , Zhou Yuwei , Zhu Jinwei , Wang Xianlong 
Published: April 2022

Background: Telomerase reverse transcriptase promoter (TERT-p) mutation has been frequently found, but associated with contrary prognosis, in both low-grade gliomas and glioblastomas. For the low-grade gliomas (Grades II-III), TERT-p mutant patients have a better prognosis than the wildtype patients, whereas for the GBMs (Grade IV), TERT-p mutation is related to a poor prognosis. We hypothesize that there exist high-risk patients in LGGs who share GBM-like molecular features, including TERT-p mutation, and need more intensive treatment than other LGGs. A molecular signature is needed to identify these high-risk patients for an accurate and timely treatment.Methods: Using the within-sample relative expression orderings of gene pairs, we identified the gene pairs with significantly stable REOs, respectively, in both the TERT-p mutant LGGs and GBMs but with opposite directions in the two groups. These reversely stable gene pairs were used as the molecular signature to stratify the LGGs into high-risk and low-risk groups.Results: A signature consisting of 21 gene pairs was developed, which can classify LGGs into two groups with significantly different overall survival. The high-risk group has a similar genetic mutation profile and a similar survival profile as GBMs, and these high-risk tumors may progress to a more malignant state.Conclusion: The 21 gene-pair signature based on REOs is capable of identifying high-risk patients in LGGs and guiding the clinical choice for appropriate and timely intervention.
Janus Kinase-2 V617F Mutation and Antiphospholipid Syndrome in Cerebral Sinus Venous Thrombosis: Natural History and Retrospective Bicenter Analysis
Authors: Orion David , Itsekson-Hayosh Ze'ev , Peretz Shlomi , Mendel Rom , Yaniv Gal , Attia Moshe , Grizim-Merkel Drorit 
Published: April 2022

BackgroundCerebral sinus venous thrombosis (CSVT) is a rare neurovascular entity, usually associated with acquired or genetic hypercoagulable states. In up to 30% of the cases it remains idiopathic. Bone marrow proliferation disorders that are associated with Janus Kinase 2 V617F mutation (JAK-2) are known causes of the systemic and cerebral thrombosis—at times despite normal blood counts—for which hematologic treatment exists. However, JAK-2 prevalence in the CSVT cases is not clear.MethodsIn this retrospective analysis, data of 236 patients with CSVT admitted to two tertiary centers between 2010 and 2020 were analyzed, with emphasis on laboratory and imaging data and clinical and interventional outcomes.ResultsA total of 236 patients were included in the analysis. The patients' median age was 42 years and the average age was 44 years (±19 years), with 59% female patients. JAK-2 positivity rate was 18% (among 77 patients tested for the mutation). Patients with normal blood counts on presentation comprised 36% of the JAK-2 positive cases. Other hypercoagulability states were also investigated, with the antiphospholipid syndrome (APLA) showing the highest prevalence (11%) followed by other etiologies including oral contraceptive use, Factor V Leiden, prothrombin mutation, and malignancy. Selected JAK-2, APLA, and prothrombin mutation cases showed a more severe clinical course.ConclusionJAK-2 mutation is underdiagnosed and its screening may be warranted in the cases of idiopathic CSVT, even despite normal blood counts, to allow disease-modifying treatment and blood cell count monitoring. JAK-2, APLA, and prothrombin mutation may be associated with a more complicated clinical course.
Predictors of Functional School Outcome in Children With Pediatric Acquired Brain Injury
Authors: Stubberud Jan , Hypher Ruth , Brandt Anne E. , Finnanger Torun G. , Skovlund Eva , Andersson Stein , Risnes Kari , Rø Torstein B. 
Published: April 2022

ObjectiveAmong the variety of domains that may be impacted after pediatric acquired brain injury (pABI) are functional school outcomes. The purpose of this study was to identify demographic, medical, and psychological factors associated with impairments in functional school outcomes, defined as school absence, need of educational and psychological services, quality of life (QoL) in the school setting, and academic performance in children with pABI, with a specific emphasis on the significance of fatigue.Materials and MethodWe used baseline data from a randomized controlled trial. The sample consisted of seventy-six children aged 10 to 17 (M = 13 yrs) with pABI in the chronic phase (&gt;1 year). All completed assessments of school-related QoL, academic performance, global functioning, fatigue, IQ, behavioral problems, and executive function.ResultsFatigue, IQ, global functioning, behavioral problems, and sex emerged as potential predictors for functional school outcomes. Of note, overall fatigue emerged as the strongest potential predictor for parent-reported QoL in school (β = 0.548; p &lt; 0.001) and self-reported QoL in school (β = 0.532; p &lt; 0.001).ConclusionsFollowing pABI, specific psychological, medical, and demographic factors are associated with functional school outcomes. Neither of the injury-related variables age at insult and time since insult were associated with functional school outcomes. Overall, our findings may suggest that a reintroduction to school with personalized accommodations tailored to the child's specific function and symptoms, such as fatigue, is recommended.