bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tenofovir Disoproxil Fumarate Is Superior to Entecavir in Reducing Hepatitis B Surface Antigen for Chronic Hepatitis B in China: 2-Year Comprehensive Comparative Result of a Matched Comparative Study
Authors: Yang Sisi , Ma Xueqing , Cai Chengwei , Wang Huanqiu , Xiao Fenqiang , Yu Chengbo 
Published: March 2021

Aim: Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are equally recommended as the first-line antiviral treatments for chronic hepatitis B (CHB) at present. We aimed to compare the long-term efficacy and safety between ETV and TDF therapy in CHB patients who had not received nucleoside analog treatment.Method: In this single-center retrospective study, 414 patients who received ETV (290 patients) or TDF (124 patients) therapy at our center from January 2017 to May 2019 were included. To reduce the imbalance of baseline variables, propensity score matching (PSM) was employed to yield 124 pairs of patients at a ratio of 1:1 based on the treatment regimen.Result: After PSM, the cumulative rate of patients who achieved complete virological response (CVR) was not different by drug therapy at each inspection time (1, 3, 6, 12, 18, and 24 months). Subgroup analysis on HBeAg status and level of HBV DNA demonstrated that evolution of proportion of achieving CVR was not significantly different between groups. Despite the insignificant incidence of HBsAg seroclearance in either group, patients in TDF group achieved higher on-treatment HBsAg decline at each inspection time (1, 3, 6, 9, 12, 18, and 24 months), 0.39, 0.51, 0.61, 0.64, 0.68, 0.76, and 0.91 log IU/mL, respectively; while the corresponding reduction were 0.27, 0.37, 0.40, 0.45, 0.48, 0.55, and 0.66 log IU/mL in ETV group (p &lt; 0.05). In subgroup analysis, we found that the significant difference still existed in patients with high baseline HBsAg level (&gt;3 log IU/mL). Additionally, the proportion of patients who achieved on-treatment HBsAg decline &gt;1 log IU/mL in TDF and ETV group was 33.3 and 17.1% (p &lt; 0.01) at the 12th month, 44.4 and 29.5% (p = 0.03) at the 24th month, respectively. Mean increase in serum creatinine from baseline was 0.10 and 0.08 mg/dL in TDF and ETV group (p = 0.11), with no patient experienced acute kidney injury.Conclusions: TDF has higher potency in reducing HBsAg than ETV in this study. Considering the effect still existed in patients with high HBsAg level (&gt;3 log IU/mL), TDF might be a superior therapeutic regimen combining with its relatively safety.
Long-Lived Species of Bivalves Exhibit Low MT-DNA Substitution Rates
Authors: Mortz Mathieu , Levivier Aurore , Lartillot Nicolas , Dufresne France , Blier Pierre U. 
Published: March 2021

Bivalves represent valuable taxonomic group for aging studies given their wide variation in longevity (from 1–2 to &gt;500 years). It is well known that aging is associated to the maintenance of Reactive Oxygen Species homeostasis and that mitochondria phenotype and genotype dysfunctions accumulation is a hallmark of these processes. Previous studies have shown that mitochondrial DNA mutation rates are linked to lifespan in vertebrate species, but no study has explored this in invertebrates. To this end, we performed a Bayesian Phylogenetic Covariance model of evolution analysis using 12 mitochondrial protein-coding genes of 76 bivalve species. Three life history traits (maximum longevity, generation time and mean temperature tolerance) were tested against 1) synonymous substitution rates (dS), 2) conservative amino acid replacement rates (Kc) and 3) ratios of radical over conservative amino acid replacement rates (Kr/Kc). Our results confirm the already known correlation between longevity and generation time and show, for the first time in an invertebrate class, a significant negative correlation between dS and longevity. This correlation was not as strong when generation time and mean temperature tolerance variations were also considered in our model (marginal correlation), suggesting a confounding effect of these traits on the relationship between longevity and mtDNA substitution rate. By confirming the negative correlation between dS and longevity previously documented in birds and mammals, our results provide support for a general pattern in substitution rates.
Performance Variability During Motor Learning of a New Balance Task in a Non-immersive Virtual Environment in Children With Hemiplegic Cerebral Palsy and Typically Developing Peers
Authors: Cheng Minxin , Anderson Michael , Levac Danielle E. 
Published: March 2021

Background:Motor impairments contribute to performance variability in children with cerebral palsy (CP) during motor skill learning. Non-immersive virtual environments (VEs) are popular interventions to promote motor learning in children with hemiplegic CP. Greater understanding of performance variability as compared to typically developing (TD) peers during motor learning in VEs may inform clinical decisions about practice dose and challenge progression.Purpose:(1) To quantify within-child (i.e., across different timepoints) and between-child (i.e., between children at the same timepoint) variability in motor skill acquisition, retention and transfer in a non-immersive VE in children with CP as compared to TD children; and (2) To explore the relationship between the amount of within-child variability during skill acquisition and learning outcomes.Methods:Secondary data analysis of 2 studies in which 13 children with hemiplegic CP and 67 TD children aged 7–14 years undertook repeated trials of a novel standing postural control task in acquisition, retention and transfer sessions. Changes in performance across trials and sessions in children with CP as compared to TD children and between younger (7–10 years) and older (11–14 years) children were assessed using mixed effects models. Raw scores were converted to z-scores to meet model distributional assumptions. Performance variability was quantified as the standard deviation of z-scores.Results:TD children outperformed children with CP and older children outperformed younger children at each session. Older children with CP had the least between-child variability in acquisition and the most in retention, while older TD children demonstrated the opposite pattern. Younger children with CP had consistently high between-child variability, with no difference between sessions. Within-child variability was highest in younger children, regardless of group. Within-child variability was more pronounced in TD children as compared to children with CP. The relationship between the amount of within-child variability in performance and performance outcome at acquisition, retention and transfer sessions was task-specific, with a positive correlation for 1 study and a negative correlation in the other.Conclusions:Findings, though preliminary and limited by small sample size, can inform subsequent research to explore VE-specific causes of performance variability, including differing movement execution requirements and individual characteristics such as motivation, attention and visuospatial abilities.
Analysis of Thrombolysis Process for Acute Ischemic Stroke in Urban and Rural Hospitals in Nova Scotia Canada
Authors: Bulmer Tessa , Volders David , Kamal Noreen 
Published: March 2021

Background: Stroke is a devastating disease, but it is treatable with alteplase or tissue plasminogen activator (tPA). The effectiveness of tPA is highly time-dependent, meaning rapid treatment is critical. Fast treatment with tPA has been reported in many urban hospitals, but hospitals in rural locations struggle to reduce treatment times. This qualitative study examines current thrombolysis processes in one urban and two rural hospitals in Nova Scotia, Canada, by mapping and comparing the treatment process in these settings for acute ischemic stroke (AIS) patients, and by analyzing the healthcare professionals views on various treatment topics.Methods: Structured interviews were conducted with healthcare professionals involved in stroke treatment across the three sites. The interviews focused on the various activities in the thrombolysis treatment at each site. Additionally, participants were asked about the following 10 topics: comfort treating acute ischemic stroke patients; perceptions about tPA; appropriate tPA treatment window; stroke patient priority; tPA availability; patient consent; urban-rural treatment differences; efficiency of their treatment process; treatment delays; and suggested process improvements. Results were analyzed using the Framework Method, as well as through the development of process maps.Results: Twenty three healthcare professionals were interviewed at 2 rural hospitals and 1 urban hospital. Acute ischemic stroke patients are triaged as the highest or urgent priority at each included site. Physicians are more hesitant to treat with tPA in rural settings. A total of 11 urban-rural treatment differences were noted by the rural sites. Additionally, 11 patient-related and 29 system treatment delays were described. A process map was developed for each site, representing the arrival by ambulance and by private vehicle pathways.Conclusions: Guidelines and clear protocols are critical in reducing treatment times and ensuring consistent access to treatment. The majority of treatment delays encountered are system delays, which can be appropriately planned for to reduce delays within the care pathway. There is a general consensus that there is an urban-rural treatment gap for acute ischemic stroke patients in Nova Scotia, and that continuing education is key in rural hospitals to improve Emergency Department (ED) physician comfort with treating patients with tPA.
Efficacy and Safety of Anti-PD-1 Plus Anlotinib in Patients With Advanced Non–Small-Cell Lung Cancer After Previous Systemic Treatment Failure—A Retrospective Study
Authors: Wang Peiliang , Fang Xiaozhuang , Yin Tianwen , Tian Hairong , Yu Jinming , Teng Feifei 
Published: March 2021

BackgroundPre-clinical and clinical evidences support that simultaneous blockade of programmed death-1 (PD-1) and vascular endothelial growth factor receptor (VEGFR) can enhance antigen-specific T-cell migration, and show tolerable toxicity with favorable antitumor activity in patients. In this study, we aimed to assess the safety and efficacy of anlotinib, a novel multitarget tyrosine kinase inhibitor for VEGFR, platelet-derived growth receptor (PDGFR), and the stem cell-factor receptor (c-Kit), combined with anti-PD-1 treatment in patients with advanced NSCLC.MethodsSixty-seven patients with previously treated advanced NSCLC receiving anti-PD-1 agents concomitant with anlotinib were retrospectively enrolled in an IRB approved study. Anti-PD-1 agents including pembrolizumab, nivolumab, camrelizumab, toripalimab, sintilimab, and tislelizumab were administered every two or three weeks until disease progression or unacceptable toxicity was reached. Anlotinib was administered orally once daily on days 1–14 of a 21-day cycle. The safety and tolerability of the combination treatment were assessed by the incidence of adverse events. The efficacy of the treatment was assessed by the tumor response and survival.ResultsWith a median follow-up period of 8.7 months, treatment-related adverse events occurred in 85% (57/67) of patients and grade 3–4 adverse events were observed in 27 patients (40%). No unexpected adverse events or significantly increased toxicities were observed. Complete response was not observed, 19 patients had partial response (28.4%), 39 had stable disease (58.2%) and 9 had progressive disease (13.4%). The overall response (ORR) and disease control rates (DCR) were 28.4% and 86.6%, respectively. The median progression-free survival (PFS) was 6.9 months (95% CI, 5.5-8.3 months) and overall survival (OS) was 14.5 months (95% CI, 10.9-18.1 months). The benefit of anti-PD-1 plus anlotinib was also observed in patients with EGFR mutation positive, liver metastases and brain metastases.ConclusionAnti-PD-1 treatment concomitant with anlotinib has tolerable toxicity and favorable antitumor activity in patients with previously treated advanced NSCLC. Our results add to the growing evidence that supports the benefits of combining immunotherapy with antiangiogenic drugs. This combination could be further evaluated with or without chemotherapy, since no additional toxicity was observed in the combination treatment.
Differentiation of Glioma Mimicking Encephalitis and Encephalitis Using Multiparametric MR-Based Deep Learning
Authors: Wu Wenli , Li Jiewen , Ye Junyong , Wang Qi , Zhang Wentao , Xu Shengsheng 
Published: March 2021

BackgroundComputational aid for diagnosis based on convolutional neural network (CNN) is promising to improve clinical diagnostic performance. Therefore, we applied pretrained CNN models in multiparametric magnetic resonance (MR) images to classify glioma mimicking encephalitis and encephalitis.MethodsA data set containing 3064 MRI brain images from 164 patients with a final diagnosis of glioma (n = 56) and encephalitis (n = 108) patients and divided into training and testing sets. We applied three MRI modalities [fluid attenuated inversion recovery (FLAIR), contrast enhanced-T1 weighted imaging (CE-T1WI) and T2 weighted imaging (T2WI)] as the input data to build three pretrained deep CNN models (Alexnet, ResNet-50, and Inception-v3), and then compared their classification performance with radiologists’ diagnostic performance. These models were evaluated by using the area under the receiver operator characteristic curve (AUC) of a five-fold cross-validation and the accuracy, sensitivity, specificity were analyzed.ResultsThe three pretrained CNN models all had AUC values over 0.9 with excellent performance. The highest classification accuracy of 97.57% was achieved by the Inception-v3 model based on the T2WI data. In addition, Inception-v3 performed statistically significantly better than the Alexnet architecture (p&lt;0.05). For Inception-v3 and ResNet-50 models, T2WI offered the highest accuracy, followed by CE-T1WI and FLAIR. The performance of Inception-v3 and ResNet-50 had a significant difference with radiologists (p&lt;0.05), but there was no significant difference between the results of the Alexnet and those of a more experienced radiologist (p &gt;0.05).ConclusionsThe pretrained CNN models can automatically and accurately classify these two diseases and further help to improving clinical diagnostic performance.
Comparison of the Simulated Response of Three in Silico Human Stem Cell-Derived Cardiomyocytes Models and in Vitro Data Under 15 Drug Actions
Authors: Paci Michelangelo , Koivumäki Jussi T. , Lu Hua Rong , Gallacher David J. , Passini Elisa , Rodriguez Blanca 
Published: March 2021

Objectives: Improvements in human stem cell-derived cardiomyocyte (hSC-CM) technology have promoted their use for drug testing and disease investigations. Several in silico hSC-CM models have been proposed to augment interpretation of experimental findings through simulations. This work aims to assess the response of three hSC-CM in silico models (Koivumäki2018, Kernik2019, and Paci2020) to simulated drug action, and compare simulation results against in vitro data for 15 drugs.Methods: First, simulations were conducted considering 15 drugs, using a simple pore-block model and experimental data for seven ion channels. Similarities and differences were analyzed in the in silico responses of the three models to drugs, in terms of Ca2+ transient duration (CTD90) and occurrence of arrhythmic events. Then, the sensitivity of each model to different degrees of blockage of Na+ (INa), L-type Ca2+ (ICaL), and rapid delayed rectifying K+ (IKr) currents was quantified. Finally, we compared the drug-induced effects on CTD90 against the corresponding in vitro experiments.Results: The observed CTD90 changes were overall consistent among the in silico models, all three showing changes of smaller magnitudes compared to the ones measured in vitro. For example, sparfloxacin 10 µM induced +42% CTD90 prolongation in vitro, and +17% (Koivumäki2018), +6% (Kernik2019), and +9% (Paci2020) in silico. Different arrhythmic events were observed following drug application, mainly for drugs affecting IKr. Paci2020 and Kernik2019 showed only repolarization failure, while Koivumäki2018 also displayed early and delayed afterdepolarizations. The spontaneous activity was suppressed by Na+ blockers and by drugs with similar effects on ICaL and IKr in Koivumäki2018 and Paci2020, while only by strong ICaL blockers, e.g. nisoldipine, in Kernik2019. These results were confirmed by the sensitivity analysis.Conclusion: To conclude, The CTD90 changes observed in silico are qualitatively consistent with our in vitro data, although our simulations show differences in drug responses across the hSC-CM models, which could stem from variability in the experimental data used in their construction.
Sodium Selenite Attenuates Balloon Injury-Induced and Monocrotaline-Induced Vascular Remodeling in Rats
Authors: Cai Changhong , Wu Yonghui , Yang Lebing , Xiang Yijia , Zhu Ning , Zhao Huan , Hu Wuming , Lv Lingchun , Zeng Chunlai 
Published: March 2021

Vascular remodeling (VR), induced by the massive proliferation and reduced apoptosis of vascular smooth muscle cells (VSMCs), is primarily responsible for many cardiovascular conditions, such as restenosis and pulmonary arterial hypertension. Sodium selenite (SSE) is an inorganic selenium, which can block proliferation and stimulate apoptosis of tumor cells; still, its protective effects on VR remains unknown. In this study, we established rat models with carotid artery balloon injury and monocrotaline induced pulmonary arterial hypertension and administered them SSE (0.25, 0.5, or 1 mg/kg/day) orally by feeding tube for 14 consecutive days. We found that SSE treatment greatly ameliorated the development of VR as evidenced by an improvement of its characteristic features, including elevation of the ratio of carotid artery intimal area to medial area, right ventricular hypertrophy, pulmonary arterial wall hypertrophy and right ventricular systolic pressure. Furthermore, PCNA and TUNEL staining of the arteries showed that SSE suppressed proliferation and enhanced apoptosis of VSMCs in both models. Compared with the untreated VR rats, lower expression of PCNA and CyclinD1, but higher levels of Cleaved Caspase-3 and Bax/Bcl-2 were observed in the SSE-treated rats. Moreover, the increased protein expression of MMP2, MMP9, p-AKT, p-ERK, p-GSK3β and β-catenin that occurred in the VR rats were significantly inhibited by SSE. Collectively, treatment with SSE remarkably attenuates the pathogenesis of VR, and this protection may be associated with the inhibition of AKT and ERK signaling and prevention of VSMC’s dysfunction. Our study suggest that SSE is a potential agent for treatment of VR-related diseases.
Self-Schemas and Self-Esteem Discrepancies in Subclinical Paranoia: The Essential Role of Depressive Symptoms
Authors: Monsonet Manel , Ballespí Sergi , Sheinbaum Tamara , Valiente Carmen , Espinosa Regina , Kwapil Thomas Richard , Barrantes-Vidal Neus 
Published: March 2021

Background : Self-concepts are being intensively investigated in relation to paranoia, but research has shown some contradictory findings. Studying subclinical phenomena in a non-clinical population should allow for a clearer understanding given that clinical confounding factors are avoided. We explored self-esteem, self-schemas, and implicit/explicit self-esteem discrepancies in three non-clinical groups with different psychopathological traits and a control group.Methods: Participants with elevated trait-paranoia (n = 41), depressive symptoms (n = 34), a combination of both traits (n = 32), and a control group (n = 71) were assessed on implicit and explicit self-esteem, self-schemas, depression, and paranoia. A dimensional approach with the total sample (n = 208) was also used to complement the information provided by the group approach.Results: All groups presented similar and positive levels of implicit self-esteem. Trait-paranoia participants had similar levels of explicit self-esteem and self-schemas compared with the control group. However, the group with a combination of trait-paranoia and depressive symptoms showed the lowest levels of positive self-schemas and self-esteem. Furthermore, this group and the control group displayed implicit/explicit self-esteem discrepancies, although in opposite directions and with different implications. The dimensional approach revealed associations of trait-paranoia and depressive symptoms with poor explicit self-esteem and self-schemas but not with implicit self-esteem.Conclusions: Trait-paranoia participants showed different self-representations depending on whether depressive symptoms were present or not. The interaction between subclinical neurotic and psychotic traits entailed a detrimental self-representation that might increase the risk for psychopathology.
ANALISIS PUTUSAN GUGATAN PERWAKILAN KELOMPOK SEBAGAI UPAYA MENDAPATKAN MENDAPATKAN JAMINAN PERLINDUNGAN HAK ATAS TANAH (Studi Putusan No. 262.Pdt.G/Class.Action/2016/PN.Jkt.Pst)
Authors: Kurniawan Itok Dwi , Ramadhan Azis Akbar , Randa Geby Christabella , Widiawati Kristiana , Sukono Septian Joddie Dwianur 
Published: March 2021

Examine more deeply regarding Class Action Filing in Indonesia which is regulated in the Supreme Court Regulation No.1 of 2002., in this analysis one of the decisions is 262.Pdt.G / Class.Action / 2016 / PN.Jkt.Pst, The decision contains a group of residents of DKI Jakarta Selatan, consisting of several groups, jointly filing a lawsuit against the law (1365 BW) against related agencies which are deemed to have caused material and immaterial losses due to the normalization of the Ciliwung River. The research used is normative descriptive and literature study. In this study will examine the Considerations of the Panel of Judges regarding the Guarantee of Protection of Land Rights based on the Basic Agrarian Law and the Law on Land Acquisition. The result of this research is that the Judge's Decision does not accommodate the Plaintiffs, so that the aspects of justice that live in the eyes of the community are not fulfilled. Keywords: Lawsuit Group Representatives, Judge's Consideration, Land Rights.
STATUS AGAMA DALAM KEHIDUPAN PUBLIK PERSPEKTIF HAM INTERNASIONAL
Authors: Junadi Yudi 
Published: March 2021

Along with the rise of religious claims as one of the solid foundations for the grounding of Human Rights (HAM), the problems confronting humanity in relation to the presence of religion, in the contemporary era tend to escalate. The current wave of globalization has not only marginalized but rather provided an opportunity for the birth of various religious transnational movements that had not been predicted before. The conception of the modern state adopted by the West which was later referred to as a model for the construction of the state in various other parts of the world, was founded on the basis of secular values that transcended traditional solidarity, among which were national equality. Apart from the black stain that has been inscribed in history, especially in the field of freedom of thought, religion at this time can be said to have a positive contribution as a source of aspiration for the parties that are suppressed. Keywords : Globalization, Freedom of Religion, International Law, Human Rights.