bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advances in juvenile adjudicative competence: A 10‐year update
Authors: Cunningham Kathryn A. 
Published: August 2020

AbstractThis article provides a comprehensive review of juvenile adjudicative competence (AC) literature published between 2010 and 2019. Publications included in this article are peer‐reviewed and disseminate original research or provide new commentary on forensic evaluation, policy, or theory. The review is organized in the following sequence: (i) factors associated with juvenile AC, (ii) evaluating juvenile AC (assessment tools and techniques, quality of evaluations, evaluation recommendations), (iii) remediation (remediation recommendations), (iv) systemic issues (inconsistency in statutes and court processes, defense attorneys' concerns about AC, age‐related issues, developmental immaturity), and (v) special topics (special populations, international research). Systemic processes and variability in statutes have contributed to current concerns regarding reliability of juvenile AC evaluation and remediation. Clear and consistent standards must be developed to address these problems. Continued research is necessary to clarify how to accurately assess juvenile AC and appropriately remediate those adjudicated incompetent. Practice and policy implications as well as future directions for research are discussed.
ZHX2 mediates proteasome inhibitor resistance via regulating nuclear translocation of NF‐κB in multiple myeloma
Authors: Jiang Jifeng , Sun Yifeng , Xu Jiadai , Xu Tianhong , Xu Zhao , Liu Peng 
Published: August 2020

AbstractBackgroundMultiple myeloma (MM) is an incurable hematological malignancy. Although proteasome inhibitors and immunomodulators have significantly improved patient outcomes, some patients respond poorly to treatment and almost all patients will relapse. Mechanisms of proteasome inhibitor resistance in multiple myeloma have not been fully elucidated. ZHX2 is a transcription regulator degraded via proteasome and presents both oncogenic or tumor suppressive effect in different cancers, however, it is still unknown that the role of ZHX2 in myeloma. In this study, we aim to demonstrate the effect and mechanism of ZHX2 on proteasome inhibitor resistance in MM.MethodsGSE24080 gene expression profile datasets from Gene Expression Omnibus (GEO) were analyzed to evaluate the relationship between ZHX2 expression level and survival in MM. Expression of ZHX2 in human MM cell lines at baseline and after bortezomib (BTZ) treatment was determined by Western blotting (WB). The proliferation and apoptosis rate of MM cells treated with BTZ after the knockdown of ZHX2 were analyzed by flow cytometry. Nuclear translocation of NF‐κB after the knockdown of ZHX2 was evaluated by WB and immunofluorescence, and the expression of NF‐κB target genes was measured by real‐time quantitative PCR. Co‐immunoprecipitation (Co‐IP) and WB were used to detect the interaction of ZHX2 with NF‐κB.ResultsWe found that higher ZHX2 expression was correlated with poorer clinical outcomes of patients. In addition, ZHX2 expression was relatively higher in RPMI‐8226 and MM.1S cell lines and the level of ZHX2 protein was upregulated after BTZ treatment. Knockdown of ZHX2 significantly enhanced the sensitivity of MM cells to BTZ, inhibited nuclear translocation of NF‐κB, and reduced mRNA expression of NF‐κB target genes. It was also revealed that ZHX2 directly binds to NF‐κB.ConclusionOur study showed that ZHX2 can promote proteasome inhibitor resistance in MM cells by regulating the nuclear translocation of NF‐κB.
Identification of potential prognostic small nucleolar RNA biomarkers for predicting overall survival in patients with sarcoma
Authors: Liu Jianwei , Liao Xiwen , Zhu Xianze , Lv Peizhen , Li Rong 
Published: August 2020

AbstractObjectiveThe main purpose of the present study is to screen prognostic small nucleolar RNA (snoRNA) markers using the RNA‐sequencing (RNA‐seq) dataset of The Cancer Genome Atlas (TCGA) sarcoma cohort.MethodsThe sarcoma RNA‐seq dataset comes from the TCGA cohort. A total of 257 sarcoma patients were included into the prognostic analysis. Multiple bioinformatics analysis methods for functional annotation of snoRNAs and screening of targeted drugs, including biological network gene ontology tool, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), and connectivity map (CMap) are used.ResultsWe had identified 15 snoRNAs that were significantly related to the prognosis of sarcoma and constructed a prognostic signature based on four prognostic snoRNA (U3, SNORA73B, SNORD46, and SNORA26) expression values. Functional annotation of these four snoRNAs by their co‐expression genes suggests that some of them were closely related to cell cycle‐related biological processes and tumor‐related signaling pathways, such as Wnt, mitogen‐activated protein kinase, target of rapamycin, and nuclear factor‐kappa B signaling pathway. GSEA of the risk score suggests that high risk score phenotype was significantly enriched in cell cycle‐related biological processes, protein SUMOylation, DNA replication, p53 binding, regulation of DNA repair, and DNA methylation, as well as Myc, Wnt, RB1, E2F, and TEL pathways. Then we also used the CMap online tool to screen five targeted drugs (rilmenidine, pizotifen, amiprilose, quipazine, and cinchonidine) for this risk score model in sarcoma.ConclusionOur study have identified 15 snoRNAs that may be serve as novel prognostic biomarkers for sarcoma, and constructed a prognostic signature based on four prognostic snoRNA expression values.
A methylomics‐associated nomogram predicts recurrence‐free survival of thyroid papillary carcinoma
Authors: Chen Hengyu , Ma Xianxiong , Yang Ming , Wang Mengyi , Li Lei , Huang Tao 
Published: August 2020

AbstractBackgroundThyroid papillary carcinoma (TPC) is the most common type of thyroid cancer (TC). The prognosis of TPC patients with tumor‐cell metastasis is poor. Therefore, this study aims to develop a model for predicting TPC patients' recurrence‐free survival (RFS).MethodsWe included 546 TPC patients who were clinically and pathologically diagnosed with TPC. The methylation biomarkers that associate with RFS were explored. These 546 samples were divided into training dataset (first 70%) and validation dataset (remaining 30%) randomly. The training dataset was used to identify prognostic biomarkers and construct risk prediction model, in addition, the validation dataset was used to verify the predictive performance of the model. We used Cox proportional hazard analysis and the least absolute shrinkage and selection operator (LASSO) Cox regression analysis to identify the significant predictive biomarkers, and establish the relapse risk prediction model from the identified biomarkers.ResultsA 6‐DNA methylation signature yielded a high evaluative performance for RFS. The Kaplan‐Meier analysis indicated that the 6‐DNA methylation signature could significantly distinguish the high‐ and low‐risk patients in training, validation and entire sets. In addition, a nomogram was constructed based on risk score, metastasis status and residual tumor status, and C‐index, receiver operating characteristic (ROC) and the calibration plots analysis which demonstrated the good performance and clinical utility of the nomogram.ConclusionsThe results suggested that the 6‐DNA methylation signature is the independent prognostic marker for RFS and functioned as a significant tool for guiding the clinical treatment of TPC patients.
Application of response surface methodology for optimization of ultrasound‐assisted solid‐liquid extraction of phenolic compounds from Cenostigma macrophyllum
Authors: Moreira Bruno Oliveira , Barbosa Filho Marco Roberto Dourado , de Carvalho Anaildes Lago , da Silva Douglas Gonçalves , Cruz Mariluze Peixoto , Yatsuda Regiane , David Jorge Mauricio 
Published: August 2020

AbstractThis study determines the optimal conditions for the ultrasound‐assisted solid‐liquid extraction (UA‐SLE) of the total phenolic compounds (TPC) of Cenostigma macrophyllum leaves. The experiments were carried out according to three‐level, four‐variable Box‐Behnken design combined with the response surface methodology (RSM). Extraction (sonication) time, liquid‐solid ratio, methanol concentration, and ultrasonic power were investigated as independent variables to obtain the optimal extraction conditions for TPC. Data were fitted to a second‐order polynomial model, and the model fitness was evaluated by the analysis of variance, which indicated the model (P < 0.0001), presenting precision and reliability with the experiments performed (R2 = 0.9947, coefficient of variance [CV] = 4.29, SD = 1.67). Individual and interactive effects of the independent variables on TPC extraction were interpreted using the proposed mathematical model. The results showed that for the maximum TPC extraction, the optimal conditions included 32 min extraction time, 29.73 mL·g−1 liquid‐solid ratio, 47.72% methanol concentration, and 145.71 W ultrasonic power. Under these optimal conditions, the predicted values were in agreement with the experimental values, thus validating the RSM model. When the optimal conditions were compared with those of conventional extraction techniques, the results showed that UA‐SLE presented significantly better results for TPC extraction (71.2% to 138.3% more efficient) and for antioxidant activity (115.0% to 179.2% more efficient). High‐performance liquid chromatography analysis of the extracts revealed that UA‐SLE did not interfere with the extract chemical composition, thus confirming that it was more effective than conventional techniques.
Planar tomography and numerical analysis for damage characterization of impact loaded RC plates
Authors: Nerger Deborah , Moosavi Robabeh , Bracklow Franz , Hering Marcus , Kühn Tino , Curbach Manfred , Hille Falk , Rogge Andreas 
Published: August 2020

AbstractThe damage analysis of reinforced concrete (RC) is of high interest for reasons of effective maintenance and structural safety of buildings. The damage structures of RC plates loaded by an impact were investigated, applying X‐ray planar tomography and finite element method (FEM). Planar tomography allows getting three‐dimensional information of the RC elements and the damage including crack, spalling, and scabbing. The FEM model validated on the tomography data justifies the application for further predictions of the damage description. In this study, we investigated concrete plates of three different thickness subjected to impacts at different low‐ and medium‐velocity, whereby the used impactor had a flat tip, which resulted in small penetrations on the front side and scabbing on the rear side. In order to quantify the damage, the damage volume and its distribution through the plate were computed and the correlations between degree of damage and impact velocity were found out.
The impact of chronic kidney disease on outcomes following peripheral vascular intervention
Authors: Narcisse Dennis I. , Weissler Elizabeth Hope , Rymer Jennifer A. , Armstrong Ehrin J. , Secemsky Eric A. , Gray William A. , Mustapha Jihad A. , Adams George L. , Ansel Gary M. , Patel Manesh R. , Jones William Schuyler 
Published: August 2020

AbstractBackgroundPatients with chronic kidney disease (CKD) have worsened clinical outcomes following percutaneous coronary intervention; however, limited evidence exists in patients undergoing peripheral vascular intervention (PVI).PurposeWe aimed to assess the effect of CKD on outcomes following PVI for symptomatic peripheral artery disease.MethodsUsing patients from the LIBERTY 360 study, we compared the rates of 30 day and 1 year major adverse vascular events (MAVE), a composite of all‐cause mortality, major amputation, and target vessel/lesion revascularization, between patients with and without CKD (estimated glomular filtration rate less than 60) following PVI. Multivariable adjustment was performed to assess for independent association between CKD and outcomes.ResultsAmong 1189 patients enrolled, 378 patients (31.8%) had CKD. At 1 year, patients with CKD had higher rates of MAVE (34.6% vs 25.6%), all‐cause mortality (11.9% vs 5.5%), and major amputation (5.9% vs 2.6%) when compared with patients without CKD (all P < .05). After adjustment, patients with CKD had higher risks of 1‐year MAVE (HR 1.30, 95% CI 1.04‐1.64; P = .023) and all‐cause mortality (HR 1.88, 95% CI 1.22‐2.91; P = .005) when compared with patients without CKD. There was no statistically significant difference in risk of major amputations (HR 1.70, 95% CI 0.91‐3.17; P = .094).ConclusionsDespite high procedural success and low amputation rates, patients with CKD remain at greater risk for MAVE and all‐cause mortality after PVI. Further research is needed to determine treatment strategies to mitigate substantial mortality risk in this vulnerable population.
A Novel Prodrug of a nNOS Inhibitor with Improved Pharmacokinetic Potential
Authors: Maccallini Cristina , Marinelli Lisa , Indorf Patrick , Cacciatore Ivana , Fantacuzzi Marialuigia , Clement Bernd , Di Stefano Antonio , Amoroso Rosa 
Published: August 2020

AbstractUnder different pathological conditions, aberrant induction of neuronal nitric oxide synthase (nNOS) generates overproduction of NO that can cause irreversible cell damage. The aim of this study was to develop an amidoxime prodrug of a potent nNOS inhibitor, the benzhydryl acetamidine. We synthesized the benzhydryl acetamidoxime, which was evaluated in vitro to ascertain the potential NOS inhibitory activity, as well as conducting bioconversion into the parent acetamidine. The prodrug was also profiled for in vitro physicochemical properties, by determining the lipophilicity, passive permeation through the human gastrointestinal tract and across the blood‐brain barrier by PAMPA, and chemical, enzymatic, and plasma stability. The obtained data demonstrate that the amidoxime prodrug shows an improved pharmacokinetic profile with respect to the acetamidine nNOS inhibitor, thus suggesting that it could be a promising lead compound to treat all those pathological conditions in which nNOS activity is dysregulated.
Changes in chronic medication adherence, costs, and health care use after a cancer diagnosis among low‐income patients and the role of patient‐centered medical homes
Authors: Spees Lisa P. , Wheeler Stephanie B. , Zhou Xi , Amin Krutika B. , Baggett Christopher D. , Lund Jennifer L. , Urick Benjamin Y. , Farley Joel F. , Reeder‐Hayes Katherine E. , Trogdon Justin G. 
Published: August 2020

BackgroundApproximately 40% of patients with cancer also have another chronic medical condition. Patient‐centered medical homes (PCMHs) have improved outcomes among patients with multiple chronic comorbidities. The authors first evaluated the impact of a cancer diagnosis on chronic medication adherence among patients with Medicaid coverage and, second, whether PCMHs influenced outcomes among patients with cancer.MethodsUsing linked 2004 to 2010 North Carolina cancer registry and claims data, the authors included Medicaid enrollees who were diagnosed with breast, colorectal, or lung cancer who had hyperlipidemia, hypertension, and/or diabetes mellitus. Using difference‐in‐difference methods, the authors examined adherence to chronic disease medications as measured by the change in the percentage of days covered over time among patients with and without cancer. The authors then further evaluated whether PCMH enrollment modified the observed differences between those patients with and without cancer using a differences‐in‐differences‐in‐differences approach. The authors examined changes in health care expenditures and use as secondary outcomes.ResultsPatients newly diagnosed with cancer who had hyperlipidemia experienced a 7‐percentage point to 11‐percentage point decrease in the percentage of days covered compared with patients without cancer. Patients with cancer also experienced significant increases in medical expenditures and hospitalizations compared with noncancer controls. Changes in medication adherence over time between patients with and without cancer were not determined to be statistically significantly different by PCMH status. Some PCMH patients with cancer experienced smaller increases in expenditures (diabetes) and emergency department use (hyperlipidemia) but larger increases in their inpatient hospitalization rates (hypertension) compared with non‐PCMH patients with cancer relative to patients without cancer.ConclusionsPCMHs were not found to be associated with improvements in chronic disease medication adherence, but were associated with lower costs and emergency department visits among some low‐income patients with cancer.
Ontogeny of the electric organ discharge and of the papillae of the electrocytes in the weakly electric fish Campylomormyrus rhynchophorus (Teleostei: Mormyridae)
Authors: Korniienko Yevheniia , Tiedemann Ralph , Vater Marianne , Kirschbaum Frank 
Published: August 2020

AbstractThe electric organ of the mormyrid weakly electric fish, Campylomormyrus rhynchophorus (Boulenger, 1898), undergoes changes in both the electric organ discharge (EOD) and the light and electron microscopic morphology as the fish mature from the juvenile to the adult form. Of particular interest was the appearance of papillae, surface specializations of the uninnervated anterior face of the electrocyte, which have been hypothesized to increase the duration of the EOD. In a 24.5 mm long juvenile the adult electric organ (EO) was not yet functional, and the electrocytes lacked papillae. A 40 mm long juvenile, which produced a short biphasic EOD of 1.3 ms duration, shows small papillae (average area 136 μm2). In contrast, the EOD of a 79 mm long juvenile was triphasic. The large increase in duration of the EOD to 23.2 ms was accompanied by a small change in size of the papillae (average area 159 μm2). Similarly, a 150 mm long adult produced a triphasic EOD of comparable duration to the younger stage (24.7 ms) but featured a prominent increase in size of the papillae (average area 402 μm2). Thus, there was no linear correlation between EOD duration and papillary size. The most prominent ultrastructural change was at the level of the myofilaments, which regularly extended into the papillae, only in the oldest specimen—probably serving a supporting function. Physiological mechanisms, like gene expression levels, as demonstrated in some Campylomormyrus species, might be more important concerning the duration of the EOD.
Administration of 5‐bromo‐2′‐deoxyuridine interferes with neuroblast proliferation and promotes apoptotic cell death in the rat cerebellar neuroepithelium
Authors: Rodríguez‐Vázquez Lucía , Martí Joaquín 
Published: August 2020

AbstractThe current study was conducted to assess whether a single administration of 5‐bromo‐2′‐deoxyuridine (BrdU) interferes with cell proliferation and leads to the activation of apoptotic cellular events in the prenatal cerebellum. BrdU effects across a wide range of doses (25–300 μg/g b.w.) were analyzed using immunohistochemical and ultrastructural procedures. The pregnant rats were injected with BrdU at embryonic day 13, and their fetuses were sacrificed from 5 to 35 hr after exposure. The quantification of several parameters such as the density of mitotic figures, and BrdU and proliferating cell nuclear antigen (PCNA)‐reactive cells showed that, in comparison with the saline injected rats, the administration of BrdU impairs the proliferative behavior of neuroepithelial cells. The above‐mentioned parameters were significantly reduced in rats injected with 100 μg/g b.w. of BrdU. The reduction was more evident using 200 μg/g b.w. The most severe effects were found with 300 μg/g b.w. of BrdU. The present findings also revealed that high doses of BrdU lead to the activation of apoptotic cellular events as evidenced by both terminal deoxynucleotidyl transferase dUTP nick‐end labeling (TUNEL) assay and immunohistochemistry for active caspase‐3. In comparison with saline rats, many apoptotic cells were found in rats injected with 100 μg/g b.w. of BrdU. The number of dying cells increased with 200 μg/g b.w. The most important number of apoptotic cells were observed in animals injected with 300 μg/g b.w. of BrdU. Ultrastructural studies confirmed the presence of neuroblasts at different stages of apoptosis.
Dendritic spine abnormalities correlate with behavioral and cognitive deficits in mouse models of Lafora disease
Authors: Taneja Komal , Ganesh Subramaniam 
Published: August 2020

AbstractLafora disease (LD) is a genetic and fatal form of neurodegenerative disorder characterized by myoclonic epilepsy and cognitive deficits. LD is caused by loss‐of‐function mutations in the EPM2A or the NHLRC1 gene. A major hallmark of LD is the presence of abnormal glycogen aggregates in neurons and other tissues. Functional studies on the genes have, therefore, mostly focused on glycogen metabolism. The physiological basis of cognitive deficits in LD is thus largely unexplored. Alterations in dendritic spine morphology are known in neurodevelopmental and neuropsychiatric disorders. We, therefore, analyzed the dendritic spine morphologies in pyramidal neurons of the hippocampal and Cortical layer V of the Epm2a or Nhlrc1 knockout mice brain. We found a significant increase in the density, length, and reduction in the width of the dendritic spines in Postnatal day 21 to 12‐month‐old LD animals. Similar observations were made in the primary cultures of neurons derived from the hippocampi of the embryonic brain, suggesting that the aberrant spine phenotype could be a developmental defect in LD. We also looked at the cognitive and behavioral deficits as a possible readout of the spine abnormalities. The LD animals exhibited hyperactivity, reduced anxiety‐like behavior, and deficits in the spatial and nonspatial memory. Such abnormalities were seen in the younger (1–2 months) as well as the older (7–8 months) age groups. Taken together, our results suggest that the dendritic spine abnormalities are primary developmental defects in the LD model and these defects might underlie some of the symptoms, including cognitive deficits, in LD.
Performance prediction for distributed graph computing
Authors: Ji Shuo , Zhao Yinliang , Li Yuxiang 
Published: August 2020

SummaryPerformance prediction for executing graph applications on distributed systems is a prerequisite to improve system performance. Especially for distributed systems optimized by sacrificing the accuracy of results to improve runtime performance, performance prediction can be used to determine accuracy‐related system parameters to achieve a tradeoff between the runtime and inaccuracy of results. This article presents an approach that predicts the runtime and inaccuracy of executing graph algorithms on bulk synchronous parallel (BSP)‐based systems to optimize system parameters by using an artificial neural network (ANN). The proposed approach samples different scales of subgraphs from the input graph by maintaining that the features of subgraphs are similar to the features of the input graph. Then it executes graph algorithm on each subgraph and extracts their runtime features. An ANN‐based performance prediction model is trained off‐line based on the extracted features and is used to predict the performance of executing graph algorithm on the complete input graph. We have validated the proposed approach by conducting single‐source shortest path, connected component, and PageRank on the BSP‐based distributed systems. The experimental results demonstrate that the prediction method can effectively predict the runtime and the inaccuracy with a relative error rate under 14% and under 25%, respectively, compared with the actual performance results.