bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute Silica Exposure Triggers Pulmonary Inflammation Through Macrophage Pyroptosis: An Experimental Simulation
Authors: Yin Haoyu , Fang Lei , Wang Lifeng , Xia Yu , Tian Jiaqi , Ma Lan , Zhang Jing , Li Ning , Li Weixiu , Yao Sanqiao , Zhang Lin 
Published: April 2022

Silica is an essential substrate of various materials, and inhaling silica induces pulmonary diseases potentially associated with macrophage pyroptosis. Utilizing silica of micro- and nano- sizes, we explored the role of macrophage pyroptosis in silica-induced pulmonary inflammation. Under the transmission electron microscopy, we found that the internalization of silica nanoparticle induced membrane rupture and increased the number of intracellular vacuoles, and both sizes of silica could suppress cell viability and proliferation. Also, silica-exposed macrophages generated higher levels of ROS, together with the upregulated expression of NLRP3, ASC, Caspase-1, GSDMD, IL-1β, and IL-6. However, the expression of these proteins was suppressed after removing ROS or NLRP3. In addition, we found increased expression of TLR4 and NF-κB responsible for silica recognition and pyroptosis priming after silica exposure. For in vivo studies, we established animal model by intratracheally instilling 5 mg of silica into mice with/without NLRP3 inhibition. Four weeks later, we found diffused infiltration of inflammatory cells and enhanced collagen hyperplasia partially reversed by additional treatment with MCC950, so as the expression of pyroptotic molecules and proinflammatory cytokines. In particular, the dual immunofluorescent staining showed co-expression of macrophage-specific biomarker F4/80 and NLRP3 within the cells, and silica of nano-size showed more potent toxicity and pathogenicity than that of the micro-sized particles both in vitro and in vivo. To sum up, macrophage pyroptosis is an upstream event of silica-induced pulmonary inflammation promoted by ROS through the TLR4/NLRP3/NF-κB signaling axis.
Effects of Virtual Reality Education on Procedural Pain and Anxiety During Venipuncture in Children: A Randomized Clinical Trial
Authors: Ryu Jung-Hee , Han Sung-Hee , Hwang Sang Mee , Lee Jiyoun , Do Sang-Hwan , Kim Jin-Hee , Park Jin-Woo 
Published: April 2022

BackgroundVenipuncture is one of the most frequent and frightening medical procedures for children. This randomized clinical trial aimed to evaluate whether pre-procedural immersive virtual reality (VR) education could decrease pain and anxiety during venipuncture procedure of children.MethodsSixty children scheduled for venipuncture at the phlebotomy unit were randomized into either the control or VR group. Before the procedure, children of the control group received conventional simple verbal instructions, whereas those of the VR group experienced a 4-min VR education regarding venipuncture. The primary outcome was the pain and anxiety of pediatric patients assessed with the children’s hospital of eastern ontario pain scale. Secondary outcomes were parental satisfaction, venipuncture time, repeated procedure and procedural difficulty rated by phlebotomists.ResultsThe pain and anxiety score during the procedure was significantly lower in the VR group than in the control group (median [IQR], 6.0 [5.0–7.0] vs. 8.0 [6.0–9.8], P = 0.001). Parental satisfaction about the procedural process were higher in the VR group than in the control group (P = 0.029), and the degree of procedural difficulty was lower in the VR group, compared to the control group (P = 0.026).ConclusionThe preprocedural VR education significantly reduced pain and anxiety of children and decreased the procedural difficulty of phlebotomists during venipuncture procedure.Clinical Trial RegistrationUniversity hospital Medical Information Network Clinical Trials Registry (registration number: UMIN000042968, date of registration: January 9, 2021, URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000049043).
Prediction Models for Conversion From Mild Cognitive Impairment to Alzheimer’s Disease: A Systematic Review and Meta-Analysis
Authors: Chen Yanru , Qian Xiaoling , Zhang Yuanyuan , Su Wenli , Huang Yanan , Wang Xinyu , Chen Xiaoli , Zhao Enhan , Han Lin , Ma Yuxia 
Published: April 2022

Background and PurposeAlzheimer’s disease (AD) is a devastating neurodegenerative disorder with no cure, and available treatments are only able to postpone the progression of the disease. Mild cognitive impairment (MCI) is considered to be a transitional stage preceding AD. Therefore, prediction models for conversion from MCI to AD are desperately required. These will allow early treatment of patients with MCI before they develop AD. This study performed a systematic review and meta-analysis to summarize the reported risk prediction models and identify the most prevalent factors for conversion from MCI to AD.MethodsWe systematically reviewed the studies from the databases of PubMed, CINAHL Plus, Web of Science, Embase, and Cochrane Library, which were searched through September 2021. Two reviewers independently identified eligible articles and extracted the data. We used the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies (CHARMS) checklist for the risk of bias assessment.ResultsIn total, 18 articles describing the prediction models for conversion from MCI to AD were identified. The dementia conversion rate of elderly patients with MCI ranged from 14.49 to 87%. Models in 12 studies were developed using the data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). C-index/area under the receiver operating characteristic curve (AUC) of development models were 0.67–0.98, and the validation models were 0.62–0.96. MRI, apolipoprotein E genotype 4 (APOE4), older age, Mini-Mental State Examination (MMSE) score, and Alzheimer’s Disease Assessment Scale cognitive (ADAS-cog) score were the most common and strongest predictors included in the models.ConclusionIn this systematic review, many prediction models have been developed and have good predictive performance, but the lack of external validation of models limited the extensive application in the general population. In clinical practice, it is recommended that medical professionals adopt a comprehensive forecasting method rather than a single predictive factor to screen patients with a high risk of MCI. Future research should pay attention to the improvement, calibration, and validation of existing models while considering new variables, new methods, and differences in risk profiles across populations.
Association Between Clinical Factors and Result of Immune Checkpoint Inhibitor Related Myasthenia Gravis: A Single Center Experience and Systematic Review
Authors: Shi Jiayu , Tan Ying , Huang Yangyu , Li Ke , Yan Jingwen , Guan Yuzhou , Zhang Li 
Published: April 2022

BackgroundNeurological immune-related adverse events (nirAEs) are rare toxicities of immune-checkpoint inhibitors (ICI). With the increase use of ICIs, incidence of nirAEs is growing, among which ICI related MG (irMG) is causing high fatality rate. Given the limited evidence, data from a large cohort of patients with irMG is needed to aid in recognition and management of this fatal complication.ObjectiveThis study aimed to summarize clinical characteristics of irMG and explore predictors of irMG clinical outcome.MethodsWe summarized our institution's patients who were diagnosed as irMG between Sep 2019 and Oct 2021. We systematically reviewed the literature through Oct 2021 to identify all similar reported patients who met inclusion criteria. As the control group, patients with idiopathic MG were used. We collected data on clinical features, management, and outcomes of both irMG and idioMG cases. Further statistical analysis was conducted.ResultsSixty three irMG patients and 380 idioMG patients were included in the final analysis. For irMG patients, six were from our institution while the rest 57 were from reported cases. The average age of irMG patients is 70.16 years old. Forty three were male. Average time from first ICI injection to symptom onset was 5.500 weeks. Eleven patients had a past history of MG. Higher MGFA classification and higher QMGS rates were observed in irMG patients compared to idioMG patients. For complication, more irMG patients had myositis or myocarditis overlapping compared to idioMG patients. The most commonly used treatment was corticosteroids for both idioMG and irMG. Twenty one patients (35%) with irMG had unfavorable disease outcome. Single variate and multivariate binary logistic regression proved that association with myocarditis, high MGFA classification or QMGS rates at first visit were negatively related to disease outcome in irMG patients.ConclusionirMG is a life-threatening adverse event. irMG has unique clinical manifestations and clinical outcome compared to idioMG. When suspicious, early evaluation of MGFA classification, QMGS rates and myositis/myocarditis evaluation are recommended.
Prediction and Identification of GPCRs Targeting for Drug Repurposing in Osteosarcoma
Authors: Tan Manli , Gao Shangzhi , Ru Xiao , He Maolin , Zhao Jinmin , Zheng Li 
Published: April 2022

BackgroundOsteosarcoma (OS) is a malignant bone tumor common in children and adolescents. The 5-year survival rate is only 67-69% and there is an urgent need to explore novel drugs effective for the OS. G protein-coupled receptors (GPCRs) are the common drug targets and have been found to be associated with the OS, but have been seldom used in OS.MethodsThe GPCRs were obtained from GPCRdb, and the GPCRs expression profile of the OS was downloaded from the UCSC Xena platform including clinical data. 10-GPCRs model signatures related to OS risk were identified by risk model analysis with R software. The predictive ability and pathological association of the signatures in OS were explored by bio-informatics analysis. The therapeutic effect of the target was investigated, followed by the investigation of the targeting drug by the colony formation experiment were.ResultsWe screened out 10 representative GPCRs from 50 GPCRs related to OS risk and established a 10-GPCRs prognostic model (with CCR4, HCRTR2, DRD2, HTR1A, GPR158, and GPR3 as protective factors, and HTR1E, OPN3, GRM4, and GPR144 as risk factors). We found that the low-risk group of the model was significantly associated with the higher survival probability, with the area under the curve (AUC) of the ROC greater than 0.9, conforming with the model. Moreover, both risk-score and metastasis were the independent risk factor of the OS, and the risk score was positively associated with the metastatic. Importantly, the CD8 T-cells were more aggregated in the low-risk group, in line with the predict survival rate of the model. Finally, we found that DRD2 was a novel target with approved drugs (cabergoline and bromocriptine), and preliminarily proved the therapeutic effects of the drugs on OS. These novel findings might facilitate the development of OS drugs.ConclusionThis study offers a satisfactory 10-GPCRs model signature to predict the OS prognostic, and based on the model signature, candidate targets with approved drugs were provided.
The Global Impact of COVID-19 on Childhood Cancer Outcomes and Care Delivery - A Systematic Review
Authors: Majeed Amna , Wright Tom , Guo Biqi , Arora Ramandeep S. , Lam Catherine G. , Martiniuk Alexandra L. 
Published: April 2022

BackgroundChildhood cancer represents a leading cause of death and disease burden in high income countries (HICs) and low-and-middle income countries (LMICs). It is postulated that the current COVID-19 pandemic has hampered global development of pediatric oncology care programs. This systematic review aimed to comprehensively review the global impact of COVID-19 on childhood cancer clinical outcomes and care delivery.MethodsA systematic search was conducted on PubMed, Embase, Medline, and the African Medical Index from inception to November 3, 2021 following PRISMA guidelines. A manual search was performed to identify additional relevant studies. Articles were selected based on predetermined eligibility criteria.FindingsThe majority of studies reported patients with cancer and COVID-19 presenting as asymptomatic (HICs: 33.7%, LMICs: 22.0%) or with primary manifestations of fever (HICs: 36.1%, LMICs: 51.4%) and respiratory symptoms (HICs: 29.6%, LMICs: 11.7%). LMICs also reported a high frequency of patients presenting with cough (23.6%) and gastrointestinal symptoms (10.6%). The majority of patients were generally noted to have a good prognosis; however the crude mortality rate was higher in LMICs when compared to HICs (8.0% vs 1.8%). Moreover, the pandemic has resulted in delays and interruptions to cancer therapies and delays in childhood cancer diagnoses in both HICs and LMICs. However, these findings were disproportionately reported in LMICs, with significant staff shortages, supply chain disruptions, and limited access to cancer therapies for patients.ConclusionsThe COVID-19 pandemic has resulted in delays and interruptions to childhood cancer therapies and delays in childhood cancer diagnoses, and disproportionately so within LMICs. This review provides lessons learned for future system-wide disruptions to care, as well as provides key points for moving forward better with care through the remainder of this pandemic.Systematic Review RegistrationCRD42021266758, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=266758
Parents' Beliefs and Behaviors About Their Children's Literacy Development: A Cross-Sectional Study in Saudi Arabia
Authors: AlAhmari Fatimah Saeed 
Published: April 2022

BackgroundA home environment that promotes learning is a significant factor in school performance in which children's parents are involved in their education. However, little study has focused on parents' reading-related beliefs or the relationship between parents' literacy beliefs and behaviors.MethodsThis cross-sectional study describes the range of parents' reported literacy beliefs and behaviors and examines whether an association exists in Saudi Arabia. It was conducted on a convenient sample of 100 parents using a web-based self-administrated shared with families in Developmental and Behavioral Pediatrics clinics at multiple sites utilizing the Parents' Perceptions of Literacy Learning Interview Schedule (PPLLIS).ResultsThere were 83 mothers and 17 fathers; 90% had a university degree or higher. Parents' beliefs ranged between 87 and 123, with a mean of 103.54 ± 8.05, indicating more holistic perceptions than skills-based ones. There was only a positive significant correlation between parents' beliefs and behaviors regarding literacy activities. However, those participating in literacy activities with their kids were more holistic parents and scored the top one-third on the PPLLIS.ConclusionParents' beliefs and their reported behaviors are found to be significantly impacted by their educational levels. Therefore, future investigations and national campaigns are encouraged to improve parents' educational levels, especially in urban areas.
Non-invasive Cardiac Output Monitoring and Assessment of Fluid Responsiveness in Children With Shock in the Emergency Department
Authors: Awadhare Pranali , Patel Radha , McCallin Tracy , Mainali Kiran , Jackson Kelly , Starke Hannah , Bhalala Utpal 
Published: April 2022

IntroductionThe assessment of fluid responsiveness is important in the management of shock but conventional methods of assessing fluid responsiveness are often inaccurate. Our study aims to evaluate changes in objective hemodynamic parameters as measured using electrical cardiometry (ICON® monitor) following the fluid bolus in children presenting with shock and to evaluate whether any specific hemodynamic parameter can best predict fluid responsiveness among children with shock.Materials and MethodsWe conducted a prospective observational study in children presenting with shock to our emergency department between June 2020 and March 2021. We collected the parameters such as heart rate (HR), respiratory rate (RR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and hemodynamic data such as cardiac output CO), cardiac index (CI), index of contractility (ICON), stroke volume (SV), stroke index (SI), corrected flow time (FTC), systolic time ratio (STR), variation of index of contractility (VIC), stroke volume variation (SVV), systemic vascular resistance (SVR), and thoracic fluid content (TFC) using the ICON monitor before and after fluid bolus (FB). We assessed percent change (Δ) and used paired-sample Student’s t-test to compare pre- and post-hemodynamic data and Mann–Whitney U-test to compare fluid responders and non-responders. P-Values &lt; 0.05 were considered statistically significant.ResultsWe recorded 42 fluid interventions in 40 patients during our study period. The median IQR age was 10.56 (4.8, 14.8) years with male/female ratio (1.2:1). There was a significant decrease in ΔRR [−1.61 (−14.8, 0); p = 0.012], ΔDBP [−5.5 (−14.4, 8); p = 0.027], ΔMAP [−2.2 (−11, 2); p = 0.018], ΔSVR [−5.8 (−20, 5.2); p = 0.025], and ΔSTR [−8.39 (−21, 3); p = 0.001] and significant increase in ΔTFC [6.2 (3.5, 11.4); p = 0.01] following FB. We defined fluid responders by an increase in SV by ≥10% after a single FB of 20 ml/kg crystalloid. Receiver operating curve analysis revealed that among all the parameters, 15% change in ICON had an excellent AUC (0.85) for the fluid responsiveness.ConclusionOur study showed significant changes in objective hemodynamic parameters, such as SVR, STR, and TFC following FB in children presenting with shock. A 15% change in ICON had an excellent predictive performance for the fluid responsiveness among our cohort of pediatric shock.
Case Report: Novel Monitoring for Anaerobic Conditions Detected by Respiratory Quotient in a Critically Ill Pediatric Patient
Authors: Hayashi Kenichiro , Matsui Hikoro 
Published: April 2022

BackgroundHyperlactemia after cardiopulmonary bypass is associated with adverse events during the early postoperative period in children. Serum lactate levels, a standard marker of anaerobic metabolism, are determined by the production, conversion and clearance of lactate, and may lag behind the anaerobic response. Here, we report a neonatal case under anaerobic conditions after cardiac surgery, whose expired gas parameters dramatically changed before a rise in blood lactate.Case PresentationA 23-day-old girl with tetralogy of Fallot was admitted to the pediatric intensive care unit after modified Blalock-Taussig shunt operation. As hemoconcentration increased and pleural fluid and ascites accumulated, we performed partial exchange transfusion to prevent shunt occlusion. Ten minutes after partial exchange transfusion, oxygen uptake and carbon dioxide production measured by indirect calorimetry suddenly dropped, while the respiratory quotient began to rise steeply before hyperlactatemia developed a few hours later.ConclusionAnalysis of expired gas in critically ill children can detect the transition from aerobic to anaerobic conditions before hyperlactatemia.
Investigation of Macular Structural and Microcirculatory Characteristics of Posterior Staphyloma in High Myopic Eyes by Swept Source Optical Coherence Tomography Angiography
Authors: Li Haoru , Wang Qingxin , Liu Yucheng , Wang Xin , He Qing , Chen Yanhui , Wei Ruihua 
Published: April 2022

Purpose: To investigate the characteristics of macular structures and microcirculation of posterior staphyloma (PS) and explored factors related to PS in eyes with high myopia.Methods: There were 114 eyes of 82 patients in this study. Using 1:1 matching of the axial length of myopic eyes, patients were divided into no PS (NPS) and PS groups. Comprehensive ophthalmic examinations were performed on all patients. Structural parameters were acquired using swept source optical coherence tomography (SS-OCT). OCT angiography (OCTA) was used to measure the microcirculation parameters. Generalized estimated equation and linear correlation analysis were used for the statistical analysis.Results: Patients with PS had a thinner retinal thickness (RT) and choroid thickness (CT) (all p &lt; 0.05) in the measurement areas and a significantly lower subfoveal scleral thickness (SFST) (p &lt; 0.001) than those without PS. Retinal deep vascular complex density (DVD) (all p &lt; 0.05) and choriocapillaris perfusion area (CCPA) (all p &lt; 0.001) were significantly lower in the measurement areas of the PS group than in those of the NPS group. There was no significant difference in the retinal superficial vascular density between the two groups. Generalized estimating equation indicated that SFST (B = 0.079, p = 0.001), parafoveal RT (B = −0.162, p = 0.041), foveal CT (B = 0.292, p = 0.013), parafoveal CT (B = −0.157, p = 0.023), foveal CCPA (B = 0.691, p = 0.003) and parafoveal CCPA (B = −0.026, p = 0.004) were significantly correlated with PS. Age (r = −0.323, p = 0.001), spherical equivalent refraction (SER) (r = 0.289, p = 0.004), subfoveal CT (r = 0.398, p &lt; 0.001), foveal DVD (r = 0.346, p &lt; 0.001), foveal CT (r = 0.429, p &lt; 0.001), and foveal CCPA (r = 0.387, p &lt; 0.001) were strongly correlated with SFST.Conclusions: The macular structures and microcirculation in the PS group were different from those in the NPS group. SFST, CT, and CCPA were significantly correlated with PS. Lower SFST in PS was correlated with abnormalities of CT and microcirculation.
A Comparative Study of Regional Homogeneity of Resting-State fMRI Between the Early-Onset and Late-Onset Recurrent Depression in Adults
Authors: Sun Ji-fei , Chen Li-mei , He Jia-kai , Wang Zhi , Guo Chun-lei , Ma Yue , Luo Yi , Gao De-qiang , Hong Yang , Fang Ji-liang , Xu Feng-quan 
Published: April 2022

BackgroundNeurobiological mechanisms underlying the recurrence of major depressive disorder (MDD) at different ages are unclear, and this study used the regional homogeneity (ReHo) index to compare whether there are differences between early onset recurrent depression (EORD) and late onset recurrent depression (LORD).MethodsEighteen EORD patients, 18 LORD patients, 18 young healthy controls (HCs), and 18 older HCs were included in the rs-fMRI scans. ReHo observational metrics were used for image analysis and further correlation of differential brain regions with clinical symptoms was analyzed.ResultsANOVA analysis revealed significant differences between the four groups in ReHo values in the prefrontal, parietal, temporal lobes, and insula. Compared with EORD, the LORD had higher ReHo in the right fusiform gyrus/right middle temporal gyrus, left middle temporal gyrus/left angular gyrus, and right middle temporal gyrus/right angular gyrus, and lower ReHo in the right inferior frontal gyrus/right insula and left superior temporal gyrus/left insula. Compared with young HCs, the EORD had higher ReHo in the right inferior frontal gyrus/right insula, left superior temporal gyrus/left insula, and left rolandic operculum gyrus/left superior temporal gyrus, and lower ReHo in the left inferior parietal lobule, right inferior parietal lobule, and left middle temporal gyrus/left angular gyrus. Compared with old HCs, the LORD had higher ReHo in the right fusiform gyrus/right middle temporal gyrus, right middle temporal gyrus/right angular gyrus, and left rolandic operculum gyrus/left superior temporal gyrus, and lower ReHo in the right inferior frontal gyrus/right insula. ReHo in the right inferior frontal gyrus/right insula of patients with LORD was negatively correlated with the severity of 17-item Hamilton Rating Scale for Depression (HAMD-17) scores (r = −0.5778, p = 0.0120).ConclusionAdult EORD and LORD patients of different ages have abnormal neuronal functional activity in some brain regions, with differences closely related to the default mode network (DMN) and the salience network (SN), and patients of each age group exhibit ReHo abnormalities relative to matched HCs.Clinical Trial Registration[http://www.chictr.org.cn/], [ChiCTR1800014277].