bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated Bioinformatics-Based Analysis of Hub Genes and the Mechanism of Immune Infiltration Associated With Acute Myocardial Infarction
Authors: Wu Yanze , Jiang Ting , Hua Jinghai , Xiong Zhiping , Chen Hui , Li Lei , Peng Jingtian , Xiong Wenjun 
Published: April 2022

BackgroundAcute myocardial infarction (AMI) is a fatal disease that causes high morbidity and mortality. It has been reported that AMI is associated with immune cell infiltration. Now, we aimed to identify the potential diagnostic biomarkers of AMI and uncover the immune cell infiltration profile of AMI.MethodsFrom the Gene Expression Omnibus (GEO) data set, three data sets (GSE48060, GSE60993, and GSE66360) were downloaded. Differentially expressed genes (DEGs) from AMI and healthy control samples were screened. Furthermore, DEGs were performed via gene ontology (GO) functional and kyoto encyclopedia of genes and genome (KEGG) pathway analyses. The Gene set enrichment analysis (GSEA) was used to analyze GO terms and KEGG pathways. Utilizing the Search Tool for Retrieval of Interacting Genes/Proteins (STRING) database, a protein–protein interaction (PPI) network was constructed, and the hub genes were identified. Then, the receiver operating characteristic (ROC) curves were constructed to analyze the diagnostic value of hub genes. And, the diagnostic value of hub genes was further validated in an independent data set GSE61144. Finally, CIBERSORT was used to represent the compositional patterns of the 22 types of immune cell fractions in AMI.ResultsA total of 71 DEGs were identified. These DEGs were mainly enriched in immune response and immune-related pathways. Toll-like receptor 2 (TLR2), interleukin-1B (IL1B), leukocyte immunoglobulin-like receptor subfamily B2 (LILRB2), Fc fragment of IgE receptor Ig (FCER1G), formyl peptide receptor 1 (FPR1), and matrix metalloproteinase 9 (MMP9) were identified as diagnostic markers with the value of p &lt; 0.05. Also, the immune cell infiltration analysis indicated that TLR2, IL1B, LILRB2, FCER1G, FPR1, and MMP9 were correlated with neutrophils, monocytes, resting natural killer (NK) cells, gamma delta T cells, and CD4 memory resting T cells. The fractions of monocytes and neutrophils were significantly higher in AMI tissues than in control tissues.ConclusionTLR2, IL1B, LILRB2, FCER1G, FPR1, and MMP9 are involved in the process of AMI, which can be used as molecular biomarkers for the screening and diagnosis of AMI. In addition, the immune system plays a vital role in the occurrence and progression of AMI.
Surgical Outcomes of Clival Chordoma Through Endoscopic Endonasal Approach: A Single-Center Experience
Authors: Chen Ge , Li Mingchu , Xu Wenlong , Wang Xu , Feng Ming , Wang Renzhi , Liu Xiaohai 
Published: April 2022

ObjectiveClival chordoma is a locally aggressive tumor with low metastatic potential. In the past decade, endoscopic endonasal approach (EEA) for clival chordoma has had a higher resection rate and a lower morbidity rate than transcranial approaches. Here, we present our initial single-center experience after EEA of clival chordomas.Patients and methodsThis study retrospectively analyzed 17 consecutive patients with clival chordoma who received EEA in our department between March 2015 and September 2021. The operation was performed by a single surgeon with EEA. The clinical and pathological characteristics were analyzed along with the surgical outcomes and complications.ResultsA total of 17 consecutive patients with clival chordoma received EEA with a median follow-up of 29.2 months (range 1-79). Gross total resection (GTR) was performed in 7 cases (41%), subtotal resection (STR) in 7 case (41%) and partially resection (PR) in 3 cases (18%). Cerebrospinal fluid leakage occurred in 2 cases (12%) and meningitis developed in 3 patients (18%) which were all successfully treated with intravenous antibiotics without any complications. There were no perioperative deaths or new focal neurological deficits postoperatively. Four in 7 patients with STR have had radiotherapy while the other three chose to be monitored. Till the last follow-up, three patients in STR group who received radiotherapy (3 in 4) had no tumor regrowth, while one in STR group with radiotherapy (1 in 4) showed tumor progression. Two patients in STR group without radiotherapy (2 in 3) showed stable tumor while the left one (1 in 3) showed tumor progression. One patient in the PR group died of tumor progression 2 years postoperation and the other one showed tumor progression and died of lung cancer 1 year postoperation. In addition, 1 in 7 patients with GTR had tumor recurrence in situ after 10 months and developed surgical pathway seeding in the spinal canal in C1 after 16 months. No recurrence occurred in the other 6 cases with GTR during the follow-up.ConclusionAlthough more cases are needed, our case series showed EEA is a safe and reliable method for clival chordoma with high resection rates and low morbidity rates. GTR without tumor residuum would improve the outcome.
Ageing Knowledge Structure in Global River Basins
Authors: Wei Yongping , Wu Shuanglei , Lu Zhixiang , Wang Xuemei , Wu Xutong , Xu Li , Sivapalan Murugesu 
Published: April 2022

Understanding the historical evolution of science development for rethinking science in the Anthropocene is crucial for our future survival. This paper analyzed the knowledge development of the top 95 most researched river basins in the Web of Science database in the past 3 decades (1987–2017) using a network metric-based framework, comprising one scalar metric and three structural metrics: equality, efficiency, and resilience. We found that the highly researched river basins accounting about 30% of total publications, including the Yangtze River and the Great Lakes, demonstrated the “ageing” knowledge structures characterized by high inequality, low efficiency, and large redundancy with continuous expansion in scales. Dominations of knowledge interactions among Environmental Sciences, Water Resources, Marine Science and Freshwater Biology contributed to this knowledge structure. Transformations of both the composition and structure of the knowledge system is required to support global river basin management in the Anthropocene.
Characterization and Risk Assessment of Airborne Polycyclic Aromatic Hydrocarbons From Open Burning of Municipal Solid Waste
Authors: Cheng Ke , Li Jing-Yu , Wang Yan , Ji Wan-Wan , Cao Yi 
Published: April 2022

In order to reveal the pollution characteristics and risk level of polycyclic aromatic hydrocarbons (PAHs) exposed to air from open burning in China, PM2.5 samples were collected from the open burning of different types of municipal solid waste (MSW). The component of MSW differed from plastics, paper, wood and bamboo, and mixed garbage. A flue gas dilution sampling system was employed to simulate open burning testing on MSW samples from different functional urban areas. Emission characteristics and health risk assessments of PAHs in PM2.5 were analyzed. The results showed that the 16 PAHs were detected ranged from 16.0 to 10,386.9 ngm−3. The total PAH concentration of wood and bamboo wastes was the highest (24,512.1 ngm−3), while that in plastics was the lowest (4,084.7 ngm−3). Speciation composition of PAHs in PM2.5 with high-molecular-weight PAHs was dominant compared to low-molecular-weight PAHs. Health risk assessment showed that the proportion of samples with the lifelong lung carcinogenic risk value greater than 10–6 was 68.7% of the totals, most of the PAHs in PM2.5 had a certain risk of cancer. The speciation of Bap posed the greatest health risks to adults and children. The carcinogenic sequence of four components of wastes was as follows: wood and bamboo &gt; mixed garbage &gt; paper &gt; plastics and the risk for adults was about 2.26 times higher than for children. Totally, the PAHs speciation of BaP, DBahA, BbF, IcdP, BaA, BkF, and Chr in PM2.5 from the open burning of MSW can bring high carcinogenic risk to human health by respiratory exposure, and the risk value of adults is higher than that of children. The findings show the different conclusion with the results of related researches on the environmental effect of waste incineration power plants or incinerators. Therein, it can provide supplementary data to evaluate the impact of open burning of MSW on ambient air quality.
Seamless Gene Correction in the Human Cystic Fibrosis Transmembrane Conductance Regulator Locus by Vector Replacement and Vector Insertion Events
Authors: Suzuki Shingo , Chosa Keisuke , Barillà Cristina , Yao Michael , Zuffardi Orsetta , Kai Hirofumi , Shuto Tsuyoshi , Suico Mary Ann , Kan Yuet W. , Sargent R. Geoffrey , Gruenert Dieter C. 
Published: April 2022

Background: Gene correction via homology directed repair (HDR) in patient-derived induced pluripotent stem (iPS) cells for regenerative medicine are becoming a more realistic approach to develop personalized and mutation-specific therapeutic strategies due to current developments in gene editing and iPSC technology. Cystic fibrosis (CF) is the most common inherited disease in the Caucasian population, caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. Since CF causes significant multi-organ damage and with over 2,000 reported CFTR mutations, CF patients could be one prominent population benefiting from gene and cell therapies. When considering gene-editing techniques for clinical applications, seamless gene corrections of the responsible mutations, restoring native “wildtype” DNA sequence without remnants of drug selectable markers or unwanted DNA sequence changes, would be the most desirable approach.Result: The studies reported here describe the seamless correction of the W1282X CFTR mutation using CRISPR/Cas9 nickases (Cas9n) in iPS cells derived from a CF patient homozygous for the W1282X Class I CFTR mutation. In addition to the expected HDR vector replacement product, we discovered another class of HDR products resulting from vector insertion events that created partial duplications of the CFTR exon 23 region. These vector insertion events were removed via intrachromosomal homologous recombination (IHR) enhanced by double nicking with CRISPR/Cas9n which resulted in the seamless correction of CFTR exon 23 in CF-iPS cells.Conclusion: We show here the removal of the drug resistance cassette and generation of seamless gene corrected cell lines by two independent processes: by treatment with the PiggyBac (PB) transposase in vector replacements or by IHR between the tandemly duplicated CFTR gene sequences.
Thickness Distributions of Mold Flux Film and Air Gap in Billet Ultra-High Speed Continuous Casting Mold Through Multiphysics Modeling
Authors: Xu Pei , Wang Sijie , Zhou Yongzhi , Chen Dengfu , Long Mujun , Duan Huamei 
Published: April 2022

The thicknesses of mold flux film and air gap are significant factors that affect the high-efficiency heat transfer, the strand lubrication and mold taper design of billet ultra-high speed continuous casting mold. Therefore, this paper established the three-dimensional fluid flow, heat transfer and solidification model, interfacial heat transfer model and two-dimensional stress-strain model to conduct multiphysics modeling. Thereby the thickness distributions of liquid slag, solid slag and air gap in the ultra-high speed billet continuous casting mold were obtained, and analyzing the effects of melting temperature of mold flux and mold taper. The results indicate that the thicknesses of liquid slag and solid slag increase and decrease respectively along the casting direction, and air gap mainly concentrates near the mold corner. The maximum thicknesses of liquid slag, air gap, and solid slag at the mold outlet are respectively 0.18 mm at the center of the strand surface (x = 0 mm), 0.28 mm at the strand corner (x = 80 mm) and 0.67 mm at x = 74 mm. The lower melting temperature of mold flux, the greater the liquid slag thicknesses and ascend from 0.14 to 0.18 mm, and conversely the maximum air gap thicknesses descend from 0.31 to 0.28 mm and existing ranges also get smaller, which is more favorable for the strand lubrication. To eliminate the air gap, the appropriate linear mold taper is 0.45% m−1 at the 6.5 m/min in casting speed.
Examining for Cavum Septum Pellucidum and Ventricular Enlargement in Retired Elite-Level Rugby League Players
Authors: Stanwell Peter , Iverson Grant L. , Van Patten Ryan , Castellani Rudolph J. , McCrory Paul , Gardner Andrew J. 
Published: April 2022

ObjectiveA cavum septum pellucidum (CSP) has been reported as a visible brain anomaly in normal individuals as well in some former combat and collision sport athletes. The appearance of CSP with fenestrations and ventricular enlargement are considered associated features of the neuropathological diagnosis of chronic traumatic encephalopathy. The current study examined CSP anatomic features and lateral ventricle size in retired elite rugby league players and controls.MethodsForty-one retired rugby league players and 41 healthy community controls, similar in age and education, underwent structural MRI scans. CSP grade, CSP length, corpus callosum septal length, and Evans' ratio (for lateral ventricle size) were rated by two of the current study authors. All participants also self-reported concussion exposure histories, depressive symptoms, daytime sleepiness, and impulsivity. They completed a neuropsychological test battery assessing premorbid intellectual functioning, attention, processing speed, language, visuospatial skills, memory, and aspects of executive functioning.ResultsThe two raters had high agreement for CSP grade (Cohen's κ = 0.80), CSP length [intraclass correlation (ICC) = 0.99], corpus callosum septal length (ICC = 0.73), the CSP/septal ratio (ICC = 0.99), and the Evans' ratio (ICC = 0.75). Twenty-five retired players (61.0%) had an abnormal CSP compared to 17 controls [41.5%; χ(1, 82)2 = 3.12, p = 0.08, odds ratio = 2.21]. The CSP/septal ratio was larger for retired players than for the controls. The Evans' ratio did not differ between the two groups. In the retired rugby league players (n = 41), those with normal (n = 16) and abnormal (n = 25) CSP grades did not differ across age, age of first exposure to collision sport, years of sport exposure, concussion history, or 23 clinical and cognitive variables.ConclusionThis study revealed a difference in the size of the CSP between retired professional rugby league players and controls. There was no significant difference in the size of the ventricles between the two groups. There were no significant differences between those with vs. without an abnormal CSP on age of first exposure to rugby league, years of exposure to repetitive neurotrauma, number of lifetime concussions, depression, impulsivity, perceived cognitive decline, or on any neuropsychological test.
Dietary Nutrition and Gut Microbiota Composition in Patients With Hypertensive Disorders of Pregnancy
Authors: Yu Jinran , Zhang Bo , Miao Tingting , Hu Haiting , Sun Yongye 
Published: April 2022

ObjectiveThe aim is to explore the intakes of dietary nutrients and the changes of gut microbiota composition among patients with hypertensive disorders of pregnancy (HDP) and provide a theoretical basis for the prevention and treatment of HDP.MethodsThis study was conducted at the Maternal and Child Health Care Hospital of Changzhou. A total of 170 pregnant women (72 patients with HDP in the case group and 98 healthy pregnant women in the control group) in the third trimester were enrolled. Dietary nutrient intakes were assessed through a food frequency questionnaire survey. Fresh fecal samples were aseptically collected, and 16S rDNA sequencing was conducted. The intakes of dietary nutrients and the diversity and relative abundance of gut microbiota were compared between pregnant women with and without HDP. A logistic regression model was used to investigate the association between differential gut microbial genera and the risk of HDP.ResultsThe daily dietary intakes of vitamin A and vitamin C in pregnant women with HDP were significantly lower than those in the control group. The relative abundances of Bacteroidota, Bacteroidaceae, and Bacteroides were increased, and the relative abundances of Actinobacteriota, Lachnospiraceae, Prevotellaceae, Bifidobacteriaceae, Blautia, Prevotella, and Bifidobacterium were decreased in women with HDP compared with those in the controls. In addition, the relative abundance of Bifidobacterium was positively correlated with dietary intakes of vitamin C and vitamin E in patients with HDP. After adjustment for confounding factors, the odds ratio (95% confidence interval) of HDP for the relative abundance of Bifidobacterium was 0.899 (0.813, 0.995).ConclusionThe composition of gut microbiota in pregnant women with HDP was significantly changed compared with that of healthy controls. The relative abundance of Bifidobacterium was negatively associated with HDP. Moreover, dietary vitamin C and gut Bifidobacterium may cooperatively contribute to reduce the risk of HDP.
Gestational Age Variation in Human Placental Drug Transporters
Authors: Goetzl Laura , Darbinian Nune , Merabova Nana , Devane Lindsay C. , Ramamoorthy Sammanda 
Published: April 2022

Patient and providers’ fear of fetal exposure to medications may lead to discontinuation of treatment, disease relapse, and maternal morbidity. Placental drug transporters play a critical role in fetal exposure through active transport but the majority of data are limited to the 3rd trimester, when the majority of organogenesis has already occurred. Our objective was to define gestational age (GA) dependent changes in protein activity, expression and modifications of five major placental drug transporters: SERT, P-gp, NET, BCRP and MRP3. Apical brush border membrane fractions were prepared from fresh 1st, 2nd and 3rd trimester human placentas collected following elective pregnancy termination or planned cesarean delivery. A structured maternal questionnaire was used to identify maternal drug use and exclude exposed subjects. Changes in placental transporter activity and expression relative to housekeeping proteins were quantified. There was evidence for strong developmental regulation of SERT, NET, P-gp, BCRP and MRP3. P-gp and BCRP decreased with gestation (r = −0.72, p &lt; 0.001 and r = −0.77, p &lt; 0.001, respectively). Total SERT increased with gestation but this increase was due to a decrease in SERT cleavage products across trimesters. Uncleaved SERT increased with GA (r = 0.89, p &lt; 0.001) while cleaved SERT decreased with GA (r = −0.94, p &lt; 0.001). Apical membrane NET overall did not appear to be developmentally regulated (r = −0.08, p = 0.53). Two forms of MRP3 were identified; the 50 kD form did not change across GA; the 160 kD form was steady in the 1st and 2nd trimester and increased in the 3rd trimester (r = 0.24, p = 0.02). The 50 kD form was expressed at higher levels. The observed patterns of SERT, NET P-gp, BCRP and MRP3 expression and activity may be associated with transporter activity or decreased placental permeability in the 1st trimester to transporter specific substrates including commonly used psychoactive medications such as anti-depressants, anti-psychotics, and amphetamines, while transport of nutrients and serotonin is important in the 1st trimester. Overall these observations are consistent with a strong protective effect during organogenesis. 3rd trimester estimates of fetal exposure obtained from cord blood likely significantly overestimate early fetal exposure to these medications at any fixed maternal dose.
SHP2 Inhibitors Show Anti-Myeloma Activity and Synergize With Bortezomib in the Treatment of Multiple Myeloma
Authors: Zhou Pan , Xiao Mengyu , Li Weiya , Sun Xiaobai , Bai Yanliang , Meng Feiying , Zhu Zunmin , Yuan Weiping , Sun Kai 
Published: April 2022

Multiple myeloma (MM) is a plasma cell malignancy that remains incurable. The protein tyrosine phosphatase SHP2 is a central node regulating RAS/mitogen-activated protein kinase (MAPK)/extracellular signal regulated kinase (ERK) signaling pathway which plays a crucial role in the pathogenesis and proteasome inhibitor (PI) resistance of MM. Several preclinical studies have demonstrated that SHP2 inhibitors exerted antitumor activity in cancer-harboring diverse mutations in the RAS pathway, offering the potential for targeting myeloma. In this study, we showed that pharmacological inhibition of SHP2 activity using SHP099 and RMC-4550 efficiently inhibited the proliferation of MM cells by inducing apoptosis and cell cycle arrest. As per the mechanism, SHP2 inhibitors activated the level of cleaved caspase3, BAK, and P21 and downregulated ERK phosphorylation in MM cells. Moreover, the blockade of SHP2 exhibited anti-myeloma effect in vivo in a mouse xenograft model. In addition, SHP2 inhibitors synergized the antineoplastic effect of bortezomib in bortezomib-sensitive MM cells and showed identical efficacy in targeting bortezomib-resistant MM cells. Overall, our findings suggest that SHP2-specific inhibitors trigger anti-myeloma activity in vitro and in vivo by regulating the ERK pathway and enhancing cytotoxicity of bortezomib, providing therapeutic benefits for both bortezomib naïve and resistant MM.
Impact of the CYP2D6 Genotype on Metoprolol Tolerance and Adverse Events in Elderly Chinese Patients With Cardiovascular Diseases
Authors: Chen Jianqiao , Zheng Jin , Zhu Zifan , Hao Benchuan , Wang Miao , Li Huiying , Cai Yulun , Wang Shiqi , Li Jun , Liu Hongbin 
Published: April 2022

The latest consensus has changed CYP2D6 genotyping among Chinese population, while its impact on metoprolol tolerance and adverse events in elderly Chinese patients with cardiovascular diseases remains unclear. In this study, we prospectively included elderly patients who started metoprolol treatment for cardiovascular indications. According to the latest consensus on CYP2D6 genotype-to-phenotype translation, the patients were categorized as normal, intermediate, or poor metabolizers (NMs, IMs, or PMs, respectively) by detecting the presence of the CYP2D6*1, *2, *5, *10, and *14. Logistic regression model was used to analyze the correlation between the CYP2D6 phenotype and incidence of adverse events, which were assessed over a 12-week period. In this study, there were 651 (62.7%) NMs, 385 (37.1%) IMs, and 3 (0.3%) PMs. After 12 weeks of follow-up, compared with NMs, IMs had the lower maintenance dose [50.0 (25.0–50.0) mg/day vs. 25.0 (25.0–50.0) mg/day, p &lt; 0.001] and lower weight-adjusted maintenance doses (0.52 ± 0.25 mg/day/kg vs. 0.42 ± 0.22 mg/day/kg, p &lt; 0.001), and had higher incidence of postural hypotension (6.0% vs. 10.9%, p = 0.006), bradycardia (21.5% vs. 28.6%, p = 0.011), asystole (0.8% vs. 3.1%, p = 0.009) and syncope (2.0% vs. 6.2%, p = 0.001). In logistic regression model, the overall incidence of adverse events was 1.37-fold larger in IMs than in NMs (odds ratio = 1.37, 95% confidence interval = 1.05–1.79, p = 0.021). We conclude that IMs have lower tolerance and higher incidence of metoprolol-related adverse events than NMs in elderly Chinese patients with cardiovascular diseases. CYP2D6 genotyping is justifiable in elderly patients to minimize the risk of adverse events and ensure the benefits of metoprolol.