bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictive Performance of Serum S100B Versus LDH in Melanoma Patients: A Systematic Review and Meta-Analysis
Authors: Janka Eszter Anna , Várvölgyi Tünde , Sipos Zoltán , Soós Alexandra , Hegyi Péter , Kiss Szabolcs , Dembrovszky Fanni , Csupor Dezső , Kéringer Patrik , Pécsi Dániel , Solymár Margit , Emri Gabriella 
Published: December 2021

BackgroundCurrently, no consensus on the use of blood tests for monitoring disease recurrence in patients with resected melanoma exists. The only meta-analysis conducted in 2008 found that elevated serum S100B levels were associated with significantly worse survival in melanoma patients. Serum LDH is an established prognostic factor in patients with advanced melanoma.ObjectiveTo compare the discriminative and prognostic ability of serum S100B with that of serum LDH in patients with melanoma.MethodsThis systematic review and meta-analysis were reported in accordance with the PRISMA Statement. The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42019137138).ResultsA quantitative analysis of data from 6 eligible studies included 1,033 patients with cutaneous melanoma. The discriminative ability of serum S100B at identifying disease relapse [pooled Area Under the ROC (AUROC) 78.64 (95% CI 70.28; 87.01)] was significantly greater than the discriminative ability of serum LDH [AUROC 64.41 (95% CI 56.05; 7278)] (p=0.013). Ten eligible studies with 1,987 patients were included in the risk of death analysis. The prognostic performance of serum S100B [pooled estimate of adjusted hazard ratio (HR) 1.78 (95% CI 1.38; 2.29)] was independent but not superior to that of serum LDH [HR 1.60 (95% CI 1.36; 2.29)].LimitationsA relatively small number of articles were eligible and there was considerable heterogeneity across the included studies.ConclusionsSerum biomarkers may provide relevant information on melanoma patient status and should be further researched. Serum S100B is a valid marker for diagnosis of melanoma recurrence.Systematic Review RegistrationThe study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42019137138).
SENP2 Reduces Hepatocellular Carcinoma Stemness and Improves Sorafenib Sensitivity Through Inactivating the AKT/GSK3β/CTNNB1 Pathway
Authors: Tang Xiaohui , Liu Bohao , Zhang Chen , Tang Wenbin , Liang Shitian , Xiao Yadan , Deng Ruoyu , Li Zhuan 
Published: December 2021

BackgroundSmall ubiquitin-like modifier specific peptidase 2 (SENP2) suppresses the progression and chemoresistance of several cancers, while few studies report its role in hepatocellular carcinoma (HCC). This study aimed to evaluate the effect of SENP2 on stemness, sorafenib sensitivity, and downstream pathway in HCC, with validation of its molecular mechanisms by compensation experiment.MethodsSENP2 was regulated by plasmid transfection; meanwhile, in a compensation experiment, protein kinase B (AKT) was activated by SC79 treatment and β-catenin (CTNNB1) was overexpressed by plasmid transfection. After modification, sorafenib sensitivity was detected by cell counting kit-8 assay; stemness was evaluated by CD133+ cell proportion and sphere formation assay.ResultsSENP2 was decreased in HCC cell lines (including Hep3B, Li7, and Huh7) compared with normal human liver epithelial cell lines, which was further reduced in HCC stem cells than in normal HCC cells. Subsequently, SENP2 overexpression inhibited CD133+ cell proportion, decreased sphere formation ability, promoted sorafenib sensitivity, suppressed AKT and glycogen synthase kinase-3β (GSK3β) phosphorylation, and reduced CTNNB1 expression in Huh7 and Hep3B cells, while SENP2 knockdown showed the reverse effects. The following compensation experiment revealed that activating AKT or overexpressing CTNNB1 promoted CD133+ cell proportion and sphere formation ability but suppressed sorafenib sensitivity in Huh7 and Hep3B cells. Moreover, activating AKT or overexpressing CTNNB1 attenuated the effect of SENP2 overexpression on stemness and sorafenib sensitivity in Huh7 and Hep3B cells.ConclusionSENP2 suppresses HCC stemness and increases sorafenib sensitivity through inactivating the AKT/GSK3β/CTNNB1 signaling pathway.
Dexmedetomidine Use in Infants Undergoing Cooling Due to Neonatal Encephalopathy (DICE Trial): A Randomized Controlled Trial: Background, Aims and Study Protocol
Authors: Baserga Mariana , DuPont Tara L. , Ostrander Betsy , Minton Stephen , Sheffield Mark , Balch Alfred H. , Bahr Timothy M. , Watt Kevin M. 
Published: December 2021

Background: Neonatal hypoxia-ischemia encephalopathy (HIE) is the leading cause of neonatal death and poor neurodevelopmental outcomes worldwide. Therapeutic hypothermia (TH), while beneficial, still leaves many HIE treated infants with lifelong disabilities. Furthermore, infants undergoing TH often require treatment for pain and agitation which may lead to further brain injury. For instance, morphine use in animal models has been shown to induce neuronal apoptosis. Dexmedetomidine is a potent α2-adrenergic receptor agonist that may be a better alternative to morphine for newborns with HIE treated with TH. Dexmedetomidine provides sedation, analgesia, and prevents shivering but does not suppress ventilation. Importantly, there is increasing evidence that dexmedetomidine has neuroprotective properties. Even though there are limited data on pharmacokinetics (PK), safety and efficacy of dexmedetomidine in infants with HIE, it has been increasingly administered in many centers.Objectives: To review the current approach to treatment of pain, sedation and shivering in infants with HIE undergoing TH, and to describe a new phase II safety and pharmacokinetics randomized controlled trial that proposes the use of dexmedetomidine vs. morphine in this population.Methods: This article presents an overview of the current management of pain and sedation in critically ill infants diagnosed with HIE and undergoing TH for 72 h. The article describes the design and methodology of a randomized, controlled, unmasked multicenter trial of dexmedetomidine vs. morphine administration enrolling 50 (25 per arm) neonates ≥36 weeks of gestation with moderate or severe HIE undergoing TH and that require pain/sedation treatment.Results and Conclusions: Dexmedetomidine may be a better alternative to morphine for the treatment of pain and sedation in newborns with HIE treated with TH. There is increasing evidence that dexmedetomidine has neuroprotective properties in several preclinical studies of injury models including ischemia-reperfusion, inflammation, and traumatic brain injury as well as adult clinical trials of brain trauma. The Dexmedetomidine Use in Infants undergoing Cooling due to Neonatal Encephalopathy (DICE) trial will evaluate whether administration of dexmedetomidine vs. morphine is safe, establish dexmedetomidine optimal dosing by collecting opportunistic PK data, and obtain preliminary neurodevelopmental data to inform a large Phase III efficacy trial with long term neurodevelopment impairment as the primary outcome.
Preschool Confusion Assessment Method for the Intensive Care Unit–Spanish (psCAM-ICU-S): Cross-Cultural Adaptation and Validation in Colombia
Authors: Pinzón-Casas Edwar , Soto-Trujillo Maira , Camargo-Agón Laura , Henao-Castaño Ángela , Gualdrón Nathalie , Bonilla-González Carolina 
Published: December 2021

Objective: The goal of the present study was to perform a cross-cultural adaptation and clinical validation of the Preschool Confusion Assessment Method for the Intensive Care Unit–Spanish (psCAM-ICU-S) for its clinical use in the Colombian Population.Methods: We designed a Cross-cultural adaptation study followed by a cross-sectional validation study at a Single-center Pediatric Intensive Care Unit (PICU) at a University Hospital in Bogotá, Colombia. The study population was children aged from 6 months to 5 years and 11 months who had been treated in the PICU with a Richmond sedation-agitation scale score of−3 or higher. A three-phase study was carried out. The first phase comprised the application of psychometric tests on the tool. In the second phase, the psCAM-ICU-S was applied to the target population. Patients were evaluated by a nurse and a pediatric intensivist using the psCAM-ICU-S; additionally, a child psychiatrist evaluated each patient using the DSM-V criteria; the psychiatrist evaluation was chosen as the gold standard for the diagnosis of delirium. In the third phase, an evaluation of the tool's effectiveness was carried out by using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and likelihood ratios. Interrater agreement was also assessed by using the Fleiss' kappa.Results: Psychometric tests established the instrument's reliability and consistency as well as the clarity of its items. A total of 31 patients were evaluated. On average, the instrument presented a sensitivity of 93.3%, specificity of 94.8%, PPV 78%, NPV 99%, a positive likelihood ratio of 19.93, and a negative ratio of 0.07. The prevalence of delirium was 16.1% by the child psychiatrist and 25.8% using de psCAM-ICU-S. We confirmed high Interrater agreement, Kappa index (0.672–0.902).Conclusions: The psCAM-ICU-S was a valid and reliable instrument for the diagnosis of delirium in critically ill pediatric patients.
Analysis of the Risk Factors in Prognosis of Kawasaki Disease With Coronary Artery Lesions
Authors: Hu Jinling , Ren Weidong 
Published: December 2021

Abstract: Kawasaki disease (KD) is one of the most common forms of systemic vasculitis in children. Pathological features include extensive inflammation of small and medium blood vessels throughout the body. The primary complication of KD is coronary artery lesions (CALs). A total of 640 children with KD were admitted to the Department of Pediatric Cardiology at Shengjing Hospital of China Medical University from January 2017 to December 2019. These patients comprised 52 coronary artery aneurysm (CAA) cases and 47 coronary artery dilation (CAD) cases. Echocardiography was performed during the acute KD phase and then at 1, 3, 6, 12, and 24 months after KD onset. Patients were divided into a poor prognosis group (n = 30) and a normal group (n = 69) based on CALs prognosis. Differences in laboratory data, clinical manifestations and coronary artery damage rates were compared between the two groups. Univariate analysis was performed on these data, and an ROC curve was used to analyze the efficacy of each risk factor. Univariate analysis revealed that age (months), number of coronary arteries involved (NACI), IgM, IgA and brain natriuretic peptide (ProBNP) levels were higher in the poor prognosis group compared with the normal group, procalcitonin (PCT) levels in the poor prognosis group were lower than in the normal group (P &lt; 0.05).Conclusion: Age ≥ 18 months, IgM ≥ 1.07g/L, IgA ≥ 0.728g/L and NCAI ≥ 3 were poor prognostic factors of KD children with CALs. These parameters can be used as a reference indicator of early prediction where combined detection might improve the accuracy and sensitivity of prediction. Follow-up should be maintained to monitor changes in the coronary artery by echocardiography.
Population Pharmacokinetic Model Development of Tacrolimus in Pediatric and Young Adult Patients Undergoing Hematopoietic Cell Transplantation
Authors: Brooks Jordan T. , Keizer Ron J. , Long-Boyle Janel R. , Kharbanda Sandhya , Dvorak Christopher C. , Friend Brian D. 
Published: December 2021

Background: With a notably narrow therapeutic window and wide intra- and interindividual pharmacokinetic (PK) variability, initial weight-based dosing along with routine therapeutic drug monitoring of tacrolimus are employed to optimize its clinical utilization. Both supratherapeutic and subtherapeutic tacrolimus concentrations can result in poor outcomes, thus tacrolimus PK variability is particularly important to consider in the pediatric population given the differences in absorption, distribution, metabolism, and excretion among children of various sizes and at different stages of development. The primary goals of the current study were to develop a population PK (PopPK) model for tacrolimus IV continuous infusion in the pediatric and young adult hematopoietic cell transplant (HCT) population and implement the PopPK model in a clinically available Bayesian forecasting tool.Methods: A retrospective chart review was conducted of 111 pediatric and young adult patients who received IV tacrolimus by continuous infusion early in the post-transplant period during HCT from February 2016 to July 2020 at our institution. PopPK model building was performed in NONMEM. The PopPK model building process included identifying structural and random effects models that best fit the data and then identifying which patient-specific covariates (if any) further improved model fit.Results: A total of 1,648 tacrolimus plasma steady-state trough concentrations were included in the PopPK modeling process. A 2-compartment structural model best fit the data. Allometrically-scaled weight was a covariate that improved estimation of both clearance and volume of distribution. Overall, model predictions only showed moderate bias, with minor under-prediction at lower concentrations and minor over-prediction at higher predicted concentrations. The model was implemented in a Bayesian dosing tool and made available at the point-of-care.Discussion: Novel therapeutic drug monitoring strategies for tacrolimus within the pediatric and young adult HCT population are necessary to reduce toxicity and improve efficacy in clinical practice. The model developed presents clinical utility in optimizing the use of tacrolimus by enabling model-guided, individualized dosing of IV, continuous tacrolimus via a Bayesian forecasting platform.
Screening for Activity Against AMPA Receptors Among Anticonvulsants—Focus on Phenytoin
Authors: Dron M. Y. , Zhigulin A. S. , Tikhonov D. B. , Barygin O. I. 
Published: December 2021

The interest in AMPA receptors as a target for epilepsy treatment increased substantially after the approval of perampanel, a negative AMPA receptor allosteric antagonist, for the treatment of partial-onset seizures and generalized tonic-clonic seizures. Here we performed a screening for activity against native calcium-permeable AMPA receptors (CP-AMPARs) and calcium-impermeable AMPA receptors (CI-AMPARs) among different anticonvulsants using the whole-cell patch-clamp method on isolated Wistar rat brain neurons. Lamotrigine, topiramate, levetiracetam, felbamate, carbamazepine, tiagabin, vigabatrin, zonisamide, and gabapentin in 100-µM concentration were practically inactive against both major subtypes of AMPARs, while phenytoin reversibly inhibited them with IC50 of 30 ± 4 μM and 250 ± 60 µM for CI-AMPARs and CP-AMPARs, respectively. The action of phenytoin on CI-AMPARs was attenuated in experiments with high agonist concentrations, in the presence of cyclothiazide and at pH 9.0. Features of phenytoin action matched those of the CI-AMPARs pore blocker pentobarbital, being different from classical competitive inhibitors, negative allosteric inhibitors, and CP-AMPARs selective channel blockers. Close 3D similarity between phenytoin and pentobarbital also suggests a common binding site in the pore and mechanism of inhibition. The main target for phenytoin in the brain, which is believed to underlie its anticonvulsant properties, are voltage-gated sodium channels. Here we have shown for the first time that phenytoin inhibits CI-AMPARs with similar potency. Thus, AMPAR inhibition by phenytoin may contribute to its anticonvulsant properties as well as its side effects.
Are the Items of the Starkstein Apathy Scale Fit for the Purpose of Measuring Apathy Post-stroke?
Authors: Hum Stanley , Fellows Lesley K. , Lourenco Christiane , Mayo Nancy E. 
Published: December 2021

Importance: Given the importance of apathy for stroke, we felt it was time to scrutinize the psychometric properties of the commonly used Starkstein Apathy Scale (SAS) for this purpose.Objectives: The objectives were to: (i) estimate the extent to which the SAS items fit a hierarchical continuum of the Rasch Model; and (ii) estimate the strength of the relationships between the Rasch analyzed SAS and converging constructs related to stroke outcomes.Methods: Data was from a clinical trial of a community-based intervention targeting participation. A total of 857 SAS questionnaires were completed by 238 people with stroke from up to 5 time points. SAS has 14 items, rated on a 4-point scale with higher values indicating more apathy. Psychometric properties were tested using Rasch partial-credit model, correlation, and regression. Items were rescored so higher scores are interpreted as lower apathy levels.Results: Rasch analysis indicated that the response options were disordered for 8/14 items, pointing to unreliability in the interpretation of the response options; they were consequently reduced from 4 to 3. Only 9/14 items fit the Rasch model and therefore suitable for creating a total score. The new rSAS was deemed unidimensional (residual correlations: &lt; 0.3), reasonably reliable (person separation index: 0.74), with item-locations uniform across time, age, sex, and education. However, 30% of scores were &gt; 2 SD above the standardized mean but only 2/9 items covered this range (construct mistargeting). Apathy (rSAS/SAS) was correlated weakly with anxiety/depression and uncorrelated with physical capacity. Regression showed that the effect of apathy on participation and health perception was similar for rSAS/SAS versions: R2 participation measures ranged from 0.11 to 0.29; R2 for health perception was ∼0.25. When placed on the same scale (0–42), rSAS value was 6.5 units lower than SAS value with minimal floor/ceiling effects. Estimated change over time was identical (0.12 units/month) which was not substantial (1.44 units/year) but greater than expected assuming no change (t: 3.6 and 2.4).Conclusion: The retained items of the rSAS targeted domains of behaviors more than beliefs and results support the rSAS as a robust measure of apathy in people with chronic stroke.
Champion Position Analysis in Short Track Speed Skating Competitions From 2007 to 2019
Authors: Sun Lixin , Guo Tianxiao , Liu Fei , Tao Kuan 
Published: December 2021

Purpose: Short track speed skating is a racing sport with racing tactics are equally crucial to speed and technical skating skills. Therefore, to investigate the relationship between starting and finishing positions for elite skaters and subsequently, explore pacing patterns for champions are necessary.Methods: To investigate a pattern of effective tactical positioning strategy, Kendall’s tau-b correlations between starting and finishing position were calculated, with 500 m races having the most positive correlation (0.347, P &lt; 0.05).Results: Furthermore, starting position distributions of winners in each round, as well as the fluctuations in champion starting positions across rounds were analyzed. Our findings showed that skaters on the first track were inclined to win the rounds in 500, 1,000, and 1,500 m (28, 28, and 22%, respectively), and the differences between starting and finishing positions for champions were minimized in semi-finals. Meanwhile, the pacing patterns were gaining more fluctuations by the increase of race distances for champions, as the average standard deviation of lap rankings equaled 0.90, 1.15, and 2.21 for 500, 1,000, and 1,500 m races, respectively.Conclusion: In conclusion, elite skaters should adopt flexible tactics at the lowest cost of energy consumption. The overall variability of lap ranking in long-distance races were distinctly higher than it in short distance.
Reliability, and Convergent and Discriminant Validity of Gaming Disorder Scales: A Meta-Analysis
Authors: Yoon Seowon , Yang Yeji , Ro Eunbin , Ahn Woo-Young , Kim Jueun , Shin Suk-Ho , Chey Jeanyung , Choi Kee-Hong 
Published: December 2021

Background: An association between gaming disorder (GD) and the symptoms of common mental disorders is unraveled yet. In this preregistered study, we quantitatively synthesized reliability, convergent and discriminant validity of GD scales to examine association between GD and other constructs.Methods: Five representative GD instruments (GAS-7, AICA, IGDT-10, Lemmens IGD-9, and IGDS9-SF) were chosen based on recommendations by the previous systematic review study to conduct correlation meta-analyses and reliability generalization. A systematic literature search was conducted through Pubmed, Proquest, Embase, and Google Scholar to identify studies that reported information on either reliability or correlation with related variables. 2,124 studies were full-text assessed as of October 2020, and 184 were quantitatively synthesized. Conventional Hedges two-level meta-analytic method was utilized.Results: The result of reliability generalization reported a mean coefficient alpha of 0.86 (95% CI = 0.85–0.87) and a mean test-retest estimate of 0.86 (95% CI = 0.81–0.89). Estimated effect sizes of correlation between GD and the variables were as follows: 0.33 with depression (k = 45; number of effect sizes), 0.29 with anxiety (k = 37), 0.30 with aggression (k = 19), –0.22 with quality of life (k = 18), 0.29 with loneliness (k = 18), 0.56 with internet addiction (k = 20), and 0.40 with game playtime (k = 53), respectively. The result of moderator analyses, funnel and forest plots, and publication bias analyses were also presented.Discussion and Conclusion: All five GD instruments have good internal consistency and test-retest reliability. Relatively few studies reported the test-retest reliability. The result of correlation meta-analysis revealed that GD scores were only moderately associated with game playtime. Common psychological problems such as depression and anxiety were found to have a slightly smaller association with GD than the gaming behavior. GD scores were strongly correlated with internet addiction. Further studies should adopt a rigorous methodological procedure to unravel the bidirectional relationship between GD and other psychopathologies.Limitations: The current study did not include gray literature. The representativeness of the five tools included in the current study could be questioned. High heterogeneity is another limitation of the study.Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42020219781].