bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lessons From the Western Atlantic Lionfish Invasion to Inform Management in the Mediterranean
Authors: Ulman Aylin , Ali Fadilah Z. , Harris Holden E. , Adel Mohammad , Mabruk Sara A. A. Al , Bariche Michel , Candelmo Allison C. , Chapman Jennifer K. , Çiçek Burak Ali , Clements Kaylin R. , Fogg Alexander Q. , Frank Stacy , Gittings Stephen R. , Green Stephanie J. , Hall-Spencer Jason M. , Hart Jim , Huber Summer , Karp Philip E. , Kyne Fabian C. , Kletou Demetris , Magno Lauryn , Rothman Shevy B. S. , Solomon Jennifer N. , Stern Nir , Yildiz Taner 
Published: April 2022

Major invasions of Indo-Pacific lionfish (Pterois volitans and P. miles) are underway in the Western Atlantic Ocean and the Mediterranean Sea. While the establishment of lionfish in the Western Atlantic is perhaps the most well-studied marine fish invasion to date, the rapidly expanding invasion in the Mediterranean is more recent and has received less attention. Here we review and synthesize successes and failures from two decades of lionfish management in the Western Atlantic to give policy recommendations for their management in the Mediterranean. Two failed approaches that were attempted multiple times in the Western Atlantic and that we advise against are (1) feeding lionfish to native fish to promote predation and (2) implementing bounty programs to incentivize lionfish harvest. Broadly, the most important management lessons that we recommend include (1) conducting routine removals by spearfishing with scuba, which can effectively suppress local abundances of lionfish; (2) encouraging the development of recreational and commercial lionfish fisheries, which can promote long-term, sustainable lionfish population control; and, (3) engaging local communities and resource users (e.g., with lionfish removal tournaments), which can concurrently achieve multiple objectives of promoting lionfish removals, market-development, research, and public education. Managers in the Western Atlantic often needed to adapt current conservation policies to enable lionfish removals in areas where spearfishing with scuba was otherwise prohibited for conservation purposes. The risk of abusing these policies was mitigated through the use of gear restrictions, diver trainings, and through participatory approaches that integrated scuba divers and stakeholder organizations in lionfish research and management. Our review of policies and practices in the Mediterranean Sea found that many of our recommended lionfish management approaches are not being done and indicate potential opportunities to implement these. We expect and fully recommend that work continues towards multinational cooperation to facilitate regional coordination of research, control, and management efforts with respect to the Mediterranean lionfish invasion. As with other major biological invasions, lionfish are unconstrained by political borders and their control will require rapid and strategic management approaches with broad cooperation among and between governments and stakeholders.
ASPM Is a Prognostic Biomarker and Correlates With Immune Infiltration in Kidney Renal Clear Cell Carcinoma and Liver Hepatocellular Carcinoma
Authors: Deng Tingting , Liu Yang , Zhuang Jialang , Tang Yizhe , Huo Qin 
Published: April 2022

BackgroundAbnormal spindle microtubule assembly (ASPM) is a centrosomal protein and that is related to a poor clinical prognosis and recurrence. However, the relationship between ASPM expression, tumor immunity, and the prognosis of different cancers remains unclear.MethodsASPM expression and its influence on tumor prognosis were analyzed using the Tumor Immune Estimation Resource (TIMER), UALCAN, OncoLnc, and Gene Expression Profiling Interactive Analysis (GEPIA) databases. The relationship between ASPM expression and tumor immunity was analyzed using the TIMER and GEPIA databases, and the results were further verified using qPCR, western blot, and multiplex quantitative immuno fluorescence.ResultsThe results showed that ASPM expression was significantly higher in most cancer tissues than in corresponding normal tissues, including kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), pancreatic adenocarcinoma (PAAD), and breast invasive carcinoma (BRCA). ASPM expression was significantly higher in late-stage cancers than in early-stages cancers (e.g., KIRC, KIRP, LIHC, LUAD, and BRCA; p &lt; 0.05), demonstrating a possible role of ASPM in cancer progression and invasion. Moreover, our data showed that high ASPM expression was associated with poor overall survival, and disease-specific survival in KIRC and LIHC (p &lt; 0.05). Besides, Cox hazard regression analysis results showed that ASPM may be an independent prognostic factor for KIRC and LIHC. ASPM expression showed a strong correlation with tumor-infiltrating B cells, CD8+ T cells, and M2 macrophages in KIRC and LIHC.ConclusionsThese findings demonstrate that the high expression of ASPM indicates poor prognosis as well as increased levels of immune cell infiltration in KIRC and LIHC. ASPM expression may serve as a novel prognostic biomarker for both the clinical outcome and immune cell infiltration in KIRC and LIHC.
Risk Factors for Resistance to Intravenous Immunoglobulin Treatment and Coronary Artery Abnormalities in a Chinese Pediatric Population With Kawasaki Disease: A Retrospective Cohort Study
Authors: Liu Jie , Huang Yanyun , Chen Cheng , Su Danyan , Qin Suyuan , Pang Yusheng 
Published: April 2022

BackgroundThe factors predicting high-risk Kawasaki disease (KD) remain unclear. Therefore, we aimed to determine the risk factors for resistance to intravenous immunoglobulin (IVIG) treatment and coronary artery aneurysm (CAA) development in a Chinese pediatric population with high-risk KD.MethodsWe compared the performances of 11 scoring systems that have been reported to predict IVIG resistance among patients with KD hospitalized from January 2013 through August 2021. Patients were risk-stratified based on the optimal scoring system. The association of baseline characteristics with IVIG treatment resistance and CAA development was investigated within the high-risk group of KD.ResultsIn total, 346 pediatric patients with KD were included, of whom 63 (18.2%) presented with IVIG resistance. The Kobayashi score and five Chinese scoring system scores (Tang et al., Yang et al., Lan et al., Liping et al., and Wu et al.) were significantly higher in the IVIG non-responsive KD group than in the IVIG responsive KD group, and the results of the receiver operating characteristic (ROC) curves analysis were observed to be highest in the Xie Liping scoring system for IVIG resistance (area under the curve, 0.650). Especially, 87 (25.1%) patients comprised the high-risk KD group based on this optimal scoring system (≥5 points). IVIG resistance was significantly associated with the total bilirubin-to-albumin ratio (B/A ratio) [odds ratio, 7.427; 95% confidence interval (CI): 1.022–53.951]. The area under the ROC was 0.703 (95% CI: 0.586–0.821), and the cutoff point was 0.383, which indicated a sensitivity and specificity for predicting treatment resistance of 58% and 80%, respectively. The serum albumin level (odds ratio, 1.401; 95% CI: 1.049–1.869) and Z score of the left main coronary artery (odds ratio, 9.023; 95% CI: 1.070–76.112) were independent predictors of CAA development.ConclusionsIn the Chinese pediatric population with KD, the Xie Liping scoring system is the most appropriate method for identifying high-risk patients, and IVIG resistance could be predicted based on the B/A ratio. Serum albumin level and Z score of the left main coronary artery at baseline were warning indicators for CAA development. More intensified or adjunctive therapies and close follow-up should be considered for high-risk patients with these risk factors.
Case Report: Diffuse Large B Cell Lymphoma After Cardiac Transplantation due to Anthracycline-Induced Dilated Cardiomyopathy in Pediatric Acute Lymphoblastic Leukemia
Authors: Xin Ning , Chunyan Cao , You Zhou , Lu Peng , Runming Jin , Fen Zhou 
Published: April 2022

Anthracycline is a first-line chemotherapy drug used to treat childhood acute leukemia, which may cause cardiac toxicity including common arrhythmia, valve disease, pericardial effusion, and even rare cardiomyopathy and cardiac failure. We reported a 2-year-old boy who was treated irregularly for acute lymphoblastic leukemia with daunorubicin. After 26 months, his left ventricular ejection fraction decreased to 40% and progressively decreased to 20–30%. Then he successfully received a heart transplant and the myocardium was confirmed with dilated cardiomyopathy. Eight months after cardiac transplantation, he was admitted again for left neck mass and was diagnosed with monomorphic diffuse large B cell lymphoma associated with Epstein-Barr virus infection by biopsy. We present this case to highlight the importance of standard chemotherapy of daunorubicin, clinical prevention, and monitoring of anthracycline-induced cardiotoxicity in acute lymphoblastic leukemia children to ensure their good prognosis and long-term life quality.
Effectiveness of Prophylactic Use of Hepatoprotectants for Tuberculosis Drug-Induced Liver Injury: A Population-Based Cohort Analysis Involving 6,743 Chinese Patients
Authors: Chen Qin , Hu Airong , Ma Aixia , Jiang Feng , Xiao Yue , Chen Yanfei , Huang Ruijian , Yang Tianchi , Zhou Jifang 
Published: April 2022

Background: Tuberculosis drug-induced liver injury (TB-DILI) is a common and potentially severe adverse drug reaction leading to treatment interruption and treatment failure. The real-world preventive effectiveness of hepatoprotective agents for DILI is not well described. The aim of the study was to evaluate the patterns of prophylactic therapies in real-world settings and risks of DILI among adult TB patients without known risk factors for DILI.Methods: This is a population-based retrospective cohort study of patients receiving first-line anti-tuberculosis drugs in the Chinese Center for Disease Control and Prevention (CDC) TB registry linked to the Ningbo Regional Health Care Database (NRHCD) between 2015 and 2020. The primary exposure was any use of chemopreventive agents including silymarin and/or glycyrrhetinic acid during the 30-day period prior to TB diagnosis (index date). The main outcome measure was the occurrence of newly onset DILI following TB treatment. Eligible patients were followed until the earliest of any DILI, treatment discontinuation, death, or end of the study period (30 June 2020). Marginal structural competing risk models and Cox models via inverse probability treatment weights using high-dimensional propensity scores were used to estimate subdistribution hazard risks (SHR) and 95% confidence intervals (CIs) for DILI risks, with adjustment for age, sex, TB-related characteristics, and comorbidities.Results: We identified a cohort of 6,743 adult patients with TB (mean age of 47.1 [SD 18.7] years; 65.80% male), of whom 2,886 (42.8%) patients received hepatoprotective agents. A total of 895 DILI events and 111 all-cause death events without DILI were observed over a median follow-up of 367 days post-TB diagnosis. The incidence rates of composite outcomes combining DILI and all-cause mortality were 248.9 and 222.3 per 1,000 person-years in the hepatoprotective agent exposed and unexposed groups (relative hazard ratio 1.35, 95% CI 1.11–1.64), respectively. The incidence rates of DILI were 223.7 and 196.1 per 1,000 person-years in the hepatoprotective agent exposed and unexposed groups (relative hazard ratio 1.38, 95% CI 1.12–1.71), respectively. Patients with any chemopreventive agent use had comparable liver function changes as evidenced by laboratory tests.Conclusion: A non-trivial number of adult patients received chemopreventive agents for TB-DILI. However, prophylactic utilization of hepatoprotective agents was not associated with a reduction in TB-DILI risks.
Propofol Augments Paclitaxel-Induced Cervical Cancer Cell Ferroptosis In Vitro
Authors: Zhao Meng-Yun , Liu Pan , Sun Chen , Pei Li-Jian , Huang Yu-Guang 
Published: April 2022

Introduction: Cervical cancer is common in women. The present standardized therapies including surgery, chemotherapy, and radiotherapy are still not enough for treatment. Propofol is the most commonly used intravenous anesthetic agent for induction and maintenance of anesthesia and has been shown to exert anti-malignancy effects on cancer cells, inducing oxidative stress and apoptosis. However, the biological effects of propofol have not yet been systematically assessed. In this study, we examined the ferroptosis-related changes caused by propofol and the chemotherapeutic agent paclitaxel besides apoptosis in vitro.Methods: Cervical cancer cell lines (C-33A and HeLa) were treated with propofol alone (1, 2, 5, 10, and 20 μg/ml) or in combination with paclitaxel (0.5, 1, and 5 μg/ml). The viability was assessed using cell counting kit-8 (CCK8), apoptosis was detected by flow cytometry, morphological changes of mitochondria were examined using transmission electron microscope (TEM), cellular reactive oxygen species (ROS), and intracellular ferrous ions were determined by fluorescence microscope or confocal microscopy. The expression and cellular localization of apoptosis and ferroptosis-related molecules were detected by Western blot and multiplex immunohistochemistry (mIHC), respectively. Calcusyn software was used to determine whether propofol has a synergistic effect with paclitaxel.Results: Propofol and paclitaxel inhibited C-33A and HeLa cell viability. There were also synergistic effects when propofol and paclitaxel were used in combination at certain concentrations. In addition, propofol promoted paclitaxel-induced cervical cancer cell death via apoptosis. ROS level and Fe2+ concentrations were also influenced by different drug treatments. Furthermore, propofol, propofol injectable emulsion, and paclitaxel induced ferroptosis-related morphological changes of mitochondria in C-33A and HeLa cells. Ferroptosis-related signaling pathways including SLC7A11/GPX4, ubiquinol/CoQ10/FSP1, and YAP/ACSL4/TFRC were found to be changed under drug treatments.Conclusion: Propofol showed synergistic anticancer effects with paclitaxel in cervical cancer cells. Propofol and paclitaxel may induce ferroptosis of cervical cancer cells besides apoptosis.
Dynamics of Erythroferrone Response to Erythropoietin in Rats
Authors: Xu Peng , Wong Raymond S. M. , Krzyzanski Wojciech , Yan Xiaoyu 
Published: April 2022

Background: Erythroferrone (ERFE) is a hormone identified recently as a master regulator connecting iron homeostasis and erythropoiesis. Serum ERFE concentrations significantly increase in animals and humans with normal or impaired kidney function after receiving exogenous erythropoiesis-stimulating agents (ESAs), which suggests it might be a predictive factor for erythropoiesis. To evaluate whether ERFE is an early, sensitive biomarker for long-term erythropoietic effects of ESAs, we investigated the relationship between ERFE dynamics and time courses of major erythropoietic responses to ESA treatment.Methods: Healthy rats received single dose and multiple doses (thrice a week for 2 weeks) of recombinant human erythropoietin (rHuEPO) at three dose levels (100, 450, and 1350 IU/kg) intravenously. The rHuEPO and ERFE concentrations in plasma were determined at a series of time points after dosing. Erythropoietic effects including red blood cell count and hemoglobin concentrations were continuously monitored for 24 days (single dose) or 60 days (multiple doses). The expansion of erythroblasts in bone marrow was quantified by flow cytometry analysis.Results: ERFE significantly increased within a few hours and return to baseline at 24 h after rHuEPO treatment. The ERFE response was enhanced after repeated treatment, which was consistent with the observed expansion of erythroblasts in the bone marrow. In addition, the dynamics of ERFE showed double peaks at approximately 2 and 10 h after rHuEPO stimulation, and the ERFE baseline displayed a significant circadian rhythm. There was a strong positive correlation between peak values of short-term ERFE responses and the long-term hemoglobin responses.Conclusion: The stimulated release of ERFE is a rapid process within 24 h. The second peak in the ERFE response to rHuEPO suggests the presence of a feedback mechanism counterregulating the ESA stimulation. The early increase of ERFE at 2 h appears to be a predictor of the hemoglobin response at 14 days after single dose of rHuEPO. Under multiple-dose regimen, the enhanced ERFE responses still correlate with the peak hemoglobin responses. The ERFE baseline also exhibits a circadian rhythm.
Evaluation of Potential Herb-Drug Interactions Between Shengmai Injection and Losartan Potassium in Rat and In Vitro
Authors: Niu Zhenchao , Qiang Tingting , Lin Wenyong , Li Yiping , Wang Keyan , Wang Dan , Wang Xiaolong 
Published: April 2022

Aim: The present study aimed to explore the potential herb-drug interactions (HDI) between Shengmai injection (SMI) and losartan potassium (LOS) based on the expression profiles of cytochromes P450 (CYP450) and drug transporters in rat and in vitro.Methods: Different concentrations of SMI were used to explore the influence of SMI on the antihypertensive efficacy of LOS in the hypertension rat model established by N (omega)-nitro-L-arginine methyl ester (L-NAME) for 4 weeks. Subsequently, the serum concentration levels of LOS and losartan carboxylic acid (EXP3174) were determined by Liquid Chromatography Mass Spectrometry (LC-MS) and pharmacokinetic analysis. Human liver microsomes, human multidrug resistance protein 1 (MDR1/P-gp), and breast cancer resistance protein (BCRP) vesicles, human embryonic kidney 293 cell line with stable expression of the organic anion transporting polypeptide 1B1 (HEK293-OATP1B1 cells) and mock-transfected HEK293 (HEK293-MOCK) cells were used to verify the effects of SMI on CYP450 enzymes and drug transporters in vitro.Results: Low, medium, and high concentrations of SMI increased the antihypertensive efficacy of LOS to varying degrees. The high dose SMI increased the half-life (t1/2), the maximum plasma concentration (Cmax), the area under the plasma concentration-time curve (AUC) from time zero to the time of the last measurable plasma concentration (AUC0-t), AUC from time zero to infinity (AUC0-∞), and mean residence time (MRT) values of LOS and decreased its apparent volume of distribution (Vd) and clearance (CL) values. The AUC0-t, AUC0-∞, and MRT of LOS were increased, whereas the CL was decreased by the medium concentration of SMI. In addition, the high, medium, and low doses of SMI increased the relative bioavailability (Frel) of LOS. SMI exhibited no significant effects on the pharmacokinetics of EXP3174. In vitro, SMI exhibited different suppressive effects on the enzyme activity levels of CYP1A2 (6.12%), CYP2B6 (2.72%), CYP2C9 (14.31%), CYP2C19 (12.96%), CYP2D6 (12.26%), CYP3A4 (3.72%), CYP2C8 (10.00–30.00%), MDR1 (0.75%), OATP1B1(2.03%), and BCRP (0.15%).Conclusion: In conclusion, SMI improved the antihypertensive efficacy of LOS in the L-NAME-induced hypertension rat model by increasing the concentration of LOS, while leaving the concentration of EXP3174 intact. SMI affected the pharmacokinetic properties of LOS by decreasing the elimination of LOS. These effects might partly be attributed to the inhibition of the activities of CYP3A4, CYP2C9, and of the drug transporters (P-gp, BCRP, and OATP1B1) by SMI, which need further scrutiny.
Single Cell RNA-Seq Analysis of Human Red Cells
Authors: Jain Vaibhav , Yang Wen-Hsuan , Wu Jianli , Roback John D. , Gregory Simon G. , Chi Jen-Tsan 
Published: April 2022

Human red blood cells (RBCs), or erythrocytes, are the most abundant blood cells responsible for gas exchange. RBC diseases affect hundreds of millions of people and impose enormous financial and personal burdens. One well-recognized, but poorly understood feature of RBC populations within the same individual are their phenotypic heterogeneity. The granular characterization of phenotypic RBC variation in normative and disease states may allow us to identify the genetic determinants of red cell diseases and reveal novel therapeutic approaches for their treatment. Previously, we discovered diverse RNA transcripts in RBCs that has allowed us to dissect the phenotypic heterogeneity and malaria resistance of sickle red cells. However, these analyses failed to capture the heterogeneity found in RBC sub-populations. To overcome this limitation, we have performed single cell RNA-Seq to analyze the transcriptional heterogeneity of RBCs from three adult healthy donors which have been stored in the blood bank conditions and assayed at day 1 and day 15. The expression pattern clearly separated RBCs into seven distinct clusters that include one RBC cluster that expresses HBG2 and a small population of RBCs that express fetal hemoglobin (HbF) that we annotated as F cells. Almost all HBG2-expessing cells also express HBB, suggesting bi-allelic expression in single RBC from the HBG2/HBB loci, and we annotated another cluster as reticulocytes based on canonical gene expression. Additional RBC clusters were also annotated based on the enriched expression of NIX, ACVR2B and HEMGN, previously shown to be involved in erythropoiesis. Finally, we found the storage of RBC was associated with an increase in the ACVR2B and F-cell clusters. Collectively, these data indicate the power of single RBC RNA-Seq to capture and discover known and unexpected heterogeneity of RBC population.
Periodontitis Is Associated With Heart Failure: A Population-Based Study (NHANES III)
Authors: Yan Yan , Mao Min , Li Yan-Qin , Chen Yong-Ji , Yu He-Dong , Xie Wen-Zhong , Huang Qiao , Leng Wei-Dong , Xiong Jie 
Published: April 2022

Objectives: The aim of this study was to investigate the relationship between periodontitis and heart failure using the Third National Health and Nutrition Examination Survey (NHANES III).Methods: Participants who had received a periodontal examination were included and investigated for the occurrence of heart failure. The included participants were divided into no/mild periodontitis and moderate/severe periodontitis groups according to their periodontal status. Weighted prevalence of heart failure was calculated, and weighted logistic regressions models were used to explore the association between periodontitis and heart failure. Possible influencing factors were then explored through subgroup analysis.Results: Compared with that of the no/mild periodontitis group, the incidence of heart failure in participants with moderate/severe periodontitis was 5.72 times higher (95% CI: 3.76–8.72, p &lt; 0.001). After adjusting for gender, age, race, body mass index, poverty income ratio, education, marital status, smoking status, drinking status, hypertension, diabetes, stroke, and asthma, the results showed that the incidence of heart failure in the moderate/severe group was 3.03 times higher (95% CI: 1.29–7.13, p = 0.012). Subgroup analysis showed that criteria, namely, male, 40–60 years old, non-Hispanic white, body mass index &gt;30, poverty income ratio ≥1, not more than 12 years of education, currently drinking, stroke but no diabetes, or asthma supported moderate/severe periodontitis as a risk factor for heart failure (p &lt; 0.05).Conclusion: According to data from this nationally representative sample from the United States, periodontitis is associated with an increased risk of heart failure.