bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Novel and Atypical Nf-Kb Proinflammatory Program Regulated by A Camkii-Proteasome Axis Is Involved in the Early Activation of Muller Glia by High Glucose
Authors: Sba Diego Ph.D. Diego , Tundo Grazia Raffaella , Mecchia Alice , Palumbo Camilla , Atzori Maria Grazia , Levati Lauretta , Caccuri Anna Maria , Cascio Paolo , Lacal Pedro , Graziani Grazia , Varano Monica , Coletta Massimiliano , Parravano Maria Cristina 
Published: December 2021

Abstract
BackgroundDiabetic retinopathy (DR) is a microvascular complication of diabetes with a heavy impact on the life-quality of subjects and with a dramatic burden for health and economic systems on a global scale.Although the pathogenesis of DR is largely unknown, several preclinical data have pointed out to a main role of Muller glia, a cell type which spans across the retina layers providing nourishment and support for Retina Ganglion Cells (RGCs), in sensing glycemia and in acquiring a proinflammatory polarization in response to this insult.ResultsBy using a validated experimental model of DR in vitro, the rMC1 cells challenged with high glucose, we uncovered the induction of an early (within minutes) and atypical NF-kB signalling pathway regulated by a CamKII-proteasome axis. Phosphorylation of proteasome subunit Rpt6 (at serine 120) by CamKII stimulated the accelerated turnover of IkBα (i.e., the natural inhibitor of p65-50 transcription factor), regardless of the phosphorylation at serine 32 which labels canonical NF-kB signalling. This event allowed the p65-p50 heterodimer to migrate into the nucleus and to induce the selective transcription of IL-8, Il-1β and MCP-1. Pharmacological inhibition of CamKII or proteasome stopped this proinflammatory program, whereas introduction of a Rpt6 phospho-dead mutant (Rpt6-S120A) stimulated a paradoxical effect on NF-kB probably through the activation of a compensatory mechanism which may involve phosphorylation of 20S α4 subunit.ConclusionsThis study introduces a novel pathway of MG activation by high glucose and casts some light on the biological relevance of proteasome post-translational modifications in modulating pathways regulated through targeted proteolysis.
In Vitro Proliferation and Long-Term Preservation of Functional Primary Rat Hepatocytes in Cell Fibers
Authors: Mazari-Arrighi Elsa , Okitsu Teru , Teramae Hiroki , Aoyagi Hoshimi , Kiyosawa Mahiro , Yano Mariko , Takeuchi Shoji 
Published: December 2021

Abstract
Primary hepatocytes are essential cellular resource for drug screening and medical transplantation. Since culture systems for them have already succeeded in reconstituting the biomimetic microenvironment, acquiring additional capabilities both to expand primary hepatocytes and to handle them easily would be expected as progress to the next stage. This paper describes a culture system for primary rat hepatocytes that is equipped with scalability and handleability relying on cell fiber technology. Cell fibers are cell-laden core-shell hydrogel microfibers; in the core regions, cells are embedded in extracellular matrix proteins, cultured three-dimensionally, and exposed to soluble growth factors in the culture medium through the hydrogel shells. By encapsulating primary rat hepatocytes within cell fibers, we first demonstrated they increase in number while keeping their viability and their hepatic specific functions for up to thirty days of subsequent culture. Then, we demonstrated the potency of the primary rat hepatocytes that proliferate in cell fibers not only as cell-based sensors to detect drugs that damage hepatic functions and hepatocellular processes but also as transplants to improve the plasma albumin concentrations of congenital analbuminemia. Therefore, our culture system could serve for innovating strategies and promising developments in applying primary hepatocytes to both pharmaceutical and medical fields.
Deep-Learning Based Analysis of Preoperative MRI Predicts Microvascular Invasion and Outcome in Hepatocellular Carcinoma
Authors: sun Bao-Ye , Gu Pei-Yi , Guan Ruo-Yu , Zhou Cheng , Lu Jian-Wei , Yang Zhang-Fu , Pan Chao , Zhou Pei-Yun , Zhu Ya-Ping , Li Jia-Rui , Wang Zhu-Tao , Gao Shan-Shan , Yi Yong , Luo Ye , Qiu Shuang-Jian 
Published: December 2021

Abstract
Background & Aims:

Preoperative prediction of microvascular invasion (MVI) is critical for treatment strategy making in patients with hepatocellular carcinoma (HCC). We aimed to develop a deep learning (DL) model based on preoperative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to predict the MVI status and clinical outcomes in patients with HCC.
Methods

We retrospectively included a total of 321 HCC patients with pathologically confirmed MVI status. Preoperative DCE-MRI of these patients were collected, annotated and further analyzed by DL in this study. A predictive model for MVI integrating DL-predicted MVI status (DL-MVI) and clinical parameters was constructed with multivariate logistic regression.
Results

Of 321 HCC patients, 136 patients were pathologically MVI absent and 185 patients were MVI present. Recurrence-free survival (RFS) and overall survival (OS) were significantly different between the DL-predicted MVI-absent and MVI-present. Among all clinical variables, only DL-predicted MVI status and AFP were independently associated with MVI: DL-MVI (odds ratio [OR]=35.738; 95% confidence interval [CI]: 14.027-91.056; p<0.001), AFP (OR=4.634, 95% CI: 2.576-8.336; p<0.001). To predict the presence of MVI, DL-MVI combined with AFP achieved an area under the curve (AUC) of 0.824.
Conclusions

Our predictive model combining DL-MVI and AFP achieved good performance for predicting MVI and clinical outcomes in patients with HCC.
Clinical Non-adherence and Its Associated Factors Among HIV Positive Pediatrics Attending Care in South Gondar Zone Public Health Facilities, Northwest Ethiopia, 2021
Authors: Tiruneh Chalie Marew , Emiru Tigabu Desie , Tibebu Nigusie Selomon , Abate Moges Wubneh , Nigat Adane Birhanu , Bantie Berihun , Belete Amsalu , Walle Belete Gelaw , Legas Getasew , Getu Bisrat Dessie 
Published: December 2021

Abstract
Background: The most important factor in the success of HIV treatment is clinical adherence. Inadequate clinical adherence is one of the factors that affect the adherence level of highly active antiretroviral treatment and its effect on suppressed viral replication. Even though data from different settings are necessary to tackle it, pieces of evidence are limited especially in the case of clinical adherence level of HIV-infected children. Hence, this study aimed to assess clinical non-adherence level and its associated factors among HIV-positive children on HAART. Methods: A multicenter cross-sectional study was conducted from July 1 to August 30, 2021, among HIV-infected children on ART in South Gondar Zone. Data were entered into Epi Data Version 4.6 and analysis was done using Statistical Package for Social Science (SPSS) Version 25. Binary logistic regression was implemented to assess the association of factors against the outcome variable and variables with p-values ≤ 0.25 in the bivariable analysis were entered into the multivariable analysis. Finally, variables with p-values less than 0.05 were considered statistically significant factors.Result-out of 384 study participants, 383 were included in this study with a response rate of 99.7%. Nearly half of the study participants 190(49.6%) were girls. The majority, 291 (76%) of caretakers were biological mothers, and 203(53%) did not have treatment supporters. One hundred seventy-nine (46.7%) of caretakers did not disclose the status of the child about the illness. The overall prevalence of non-adherence among children on ART was 31.9 %( 95% CI: 27.2-36.6). Rural residency, diagnostic status non-disclosure, no adherence supporter, having no biological caretaker and comorbid illness were significantly associated with clinical non-adherence of HIV positive children.Conclusion-clinical non-adherence among children among HIV-positive children attending care in south Gondar zone health institutes is unacceptably high. Being rural residency, diagnostic status non-disclosure, no adherence supporter, having non-biological caretaker, and having comorbid illness were significantly associated with clinical non-adherence. Thus, attention shall be given to successful clinical adherence in HIV-positive children who uses the antiretroviral drug.
Investigation on Strain Rate Sensitivity of 3D Printed sPEEK-HAP/rGO Composites
Authors: Baligidad Sagar Mahalingappa , Gangadhara Chethan Kumar , Chandrashekhar Maharudresh Aralikatte 
Published: December 2021

Abstract
Nanofillers can be added to polymers to improve their mechanical behavior. However, the yield behaviour of most polymer composites is influenced by strain rate. The majority of the research focused on the behaviour of polymer composites at high strain rates. This work aims to investigate how hydroxyapatite (HAP) and reduced Graphene Oxide (rGO) nanofillers affect the mechanical properties of sulphonated polyetheretherketone (sPEEK) at low (tensile and compression behaviour) and high strain rates (compression behaviour). The thermal, mechanical, and energy absorption responses of sPEEK filled with HAP and varying mass fraction (Mf) of rGO (0.5%, 1%, and 1.5%) at different strain are studied in detail. The strong strain rate effect was seen in HAp and rGO loaded sPEEK composites. The strain rate sensitivity factor of sPEEK-HAP/rGO improved as the strain rate increased, but decreased when the Mf of rGO increased. Under low strain rate compression, HAp and rGO loaded sPEEK absorbed more energy at Mf about 4%. SEM micrography was used to study the microstructures of the fractured interfaces of the components, revealing that the HAp and sPEEK materials formed a good compatibility in presence of rGO.
Conditional Loss of Ikkα in Sp7/osterix+ Cells Has No Effect on Bone, but Leads to Cell Autonomous, Age-related Loss of Peripheral Fat
Authors: Davis Jennifer L , Pokhrel Nitin K , Cox Linda , Faccio Roberta , Veis Deborah J 
Published: December 2021

Abstract
NF-κB has been reported to both promote and inhibit bone formation. To further explore its role in osteolineage cells, we conditionally deleted IKKα, an upstream kinase required for non-canonical NF-κB activation, using Sp7/Osterix (Osx)-Cre. Surprisingly, we found no effect on either cancellous or cortical bone, even following mechanical loading. However, we noted that IKKα conditional knockout (cKO) mice began to lose body weight after 6 months of age with severe reductions in fat mass in geriatric animals. Low levels of recombination at the IKKα locus were detected in fat pads isolated from 15 month old cKO mice. To determine if these effects were mediated by unexpected deletion of IKKα in peripheral adipocytes, we looked for Osx-Cre-mediated recombination in fat using reporter mice, which showed increasing degrees of reporter activation in adipocytes with age up to 18 months. Since Osx-Cre-driven recombination in peripheral adipocytes increases over time, we conclude that loss of fat in aged cKO mice is most likely caused by progressive deficits of IKKα in adipocytes. To further explore the effect of IKKα loss on fat metabolism, we challenged mice with a high fat diet at 2 months of age, finding that cKO mice gained less weight and showed improved glucose metabolism, compared to littermate controls. Thus, Osx-Cre mediated recombination beyond bone, including within adipocytes, should be considered as a possible explanation for extraskeletal phenotypes, especially in aging and metabolic studies.
Systematic exploration of prognostic alternative splicing events related to immune microenvironment of Clear Cell Renal Cell Carcinoma
Authors: Deng Youyuan , Wang Jianguo , Pang Yanrui , Li Jingyong , Zhang Huaixiao , Chen Jiawei , Fang Kun , Zhou Wei , Xu Ke , Ren Tao 
Published: December 2021

Abstract
Background

Clear cell renal cell carcinoma (ccRCC) accounts for almost 75% of all renal cancers, with high heterogeneity and poor prognosis. There is increasing evidence that alternative splicing (AS) is associated with tumorigenesis and immune microenvironment. However, studies on the relationship between AS events and immunity in ccRCC are still few but needed.
Methods

The transcriptional data and clinicopathological information of ccRCC patients were downloaded from The Cancer Genome Atlas (TCGA) database. We grouped patients according to the ESTIMATE algorithm and identified for differentially expressed AS events (DEASs). The functional enrichment analysis and unsupervised consensus analysis were performed to investigate the association between AS events and immune features. The regulatory network of survival-related AS events and intersection SFs was used to explore potential mechanisms.
Results

In total, 515 ccRCC patients were included in the present study. The low immune-score group had longer overall survival (OS) than the high low immune-score group. 861 AS events were identified as DEASs, and they were enriched in immune-related pathways. Unsupervised clustering analysis revealed that AS-based clusters significantly corelated with prognosis and immune features of ccRCC. Finally, MBNL1 was identified as a hub SF, and it was shown to inhibit proliferation and metastasis, promote apoptosis, and block cells in G2/M phase in 786O and A498 cells.
Conclusion

The present systematic exploration elaborated that not only some critical AS events were related to prognosis and immune microenvironment of ccRCC, but also the hub SF, such as MBNL1, could affect the development and progression of ccRCC.
Long-Term Trend of Polycyclic Aromatic 1 Hydrocarbon (PAH) Concentrations in Tokyo from 2007 to 2016: Effects of Changes in PAH Emissions and Degradation.
Authors: Shimada Kojiro , Nohchi Masayuki , Maeshima Koji , Uchino Tomonori , Kobayashi Yusuke , Ono Kazuki , Ogata Hiroko , Katsumi Naoya , Inazu Koji , Okochi Hiroshi 
Published: December 2021

Abstract
The concentrations of polycyclic aromatic hydrocarbons (PAHs) in aerosol were measured in Shinjuku, which is central Tokyo, Japan, for 10 years from 2007 to 2016. The effects of changes in emission sources and their degradation by reaction with ozone were assessed in this study. There was no significant increasing or decreasing trend of the PAH concentrations during 10 years (P > 0.05). The average selected seven the PAH concentrations (0.88 ng m−3) during 10 years was lower than those in New York and Paris. However, the trend of ozone concentrations is increasing in central Tokyo. This inconsistency raises a question. Did the fact that the ozone concentration was higher than the PAH concentrations promote PAH degradation? To apportion the PAH sources, we used PAH concentration profiles and positive matrix factorization analysis. The contribution of vehicle emissions to the PAHs ranged from 40 to 80 %. Ozone concentrations increased by 3.70 %/year during 10 years. The theoretical degradation rates of PAHs by ozone, which were calculated using a pseudo-first-order rate equation, suggested that the lifetimes of benzo[a]pyrene (BaP) decreased by 1 min from 2007 to 2016. We investigated the aging of BaP using the profile of the isomer ratios. We found that the aging of BaP at the urban and roadside sites were nearly identical indicating aging regardless of the season. Although the decomposition of BaP is promoted by the photochemical oxidation reaction, this result suggests that a certain threshold value exists as the degree of the decomposition. This degradation of PAH can improve chemical loss processes in air quality model.
New Interpretations of The State Function of An Elementary Particle Based On The Origin of Quantum Probability
Authors: Wen Shuming 
Published: December 2021

Abstract
The theoretical results of quantum mechanics (QM) have been verified by experiments, but the probabilistic Copenhagen interpretation is still controversial, and many counterintuitive phenomena are still difficult to understand. To trace the origin of probability in QM, we construct the state function of a multiparticle quantum objective system and find that the probability in QM originates from the particle number distribution rate in a unit volume near position r at time t in the multiparticle quantum objective system. Based on the origin of probability, We find that the state function of the particle has precise physical meaning; that is, the particle periodically and alternately exhibits the particle state and wave state in time and space, obtain the localized and nonlocalized spatiotemporal range of the particle, the apparent trajectory of the particle motion. Based on this, through rigorous mathematical derivation and analysis, we propose new physical interpretations of the quantum superposition state, wave-particle duality, the double-slit experiment, the Heisenberg uncertainty principle, and the quantum tunnelling effect, and these interpretations are physically logical and not counterintuitive.
The Increased In Vivo Firing of Pyramidal Cells But not Interneurons in the Anterior Cingulate Cortex After Neuropathic Pain
Authors: Zhu Da-Yu , Cao Ting-Ting , Fan Hong-Wei , Zhang Ming-Zhe , Duan Hao-Kai , Li Jing , Li Yun-Qing , Wang Pan , Chen Tao 
Published: December 2021

Abstract
Chronic pain damages the balance between excitation and inhibition in the sensory cortex. It has been confirmed that the activity of cortical glutamatergic pyramidal cells increases after chronic pain. However, whether the activity of inhibitory interneurons synchronized changed remains obscure, especially in in vivo conditions. In the present study, we checked the firing rate of pyramidal cells and interneurons in the anterior cingulate cortex, a main cortical area for the regulation of nociceptive information in mice with spared nerve injury by using in vivo multi-channel recording system. We found that the firing rate of pyramidal cells but not interneurons increased in the ACC, which is further confirmed by the increased FOS expression in pyramidal cells but not interneurons, in mice with neuropathic pain. Selectively high frequency stimulation of the ACC nociceptive afferent fibers only potentiated the activity of pyramidal cells either. Our results thus suggest that the increased activity of pyramidal cells contributes to the damaged E/I balance in the ACC and is important for the pain hypersensitivity in mice with neuropathic pain.
The potential contribution of projected ASEAN Power Grid to emission reduction
Authors: Budiman Ibnu , Swandaru Akbar , Suryadi Beni 
Published: December 2021

Abstract
This paper analyzed the potential contribution of the projected ASEAN Power Grid (APG) with increased contribution of renewable energy (RE) in the power system, toward emission reduction in South East Asia, both in region and country level, in three different scenarios (Baseline, ASEAN Target, and Optimum RE). Data collection was done with a series of (co-creation) consultation meetings with countries in the region and international energy institutes. Estimation of emission reduction from CO2 and N2O was calculated based on projected solar and wind capacity addition to replace fossil fuel consumption in the APG. We found that the potential contribution of the projected APG toward emission reduction in South East Asia is up to 112,267 million tons of CO2 and 64 thousand tons of N2O by 2040, under the optimum RE scenario. The source of that contribution is varying at the country level. Countries with potential significant contributions are Thailand, the Philippines, Vietnam, Malaysia, and Indonesia. Countries like Singapore and Brunei that have a relatively small contribution to the region, also having progressive trends to meet the RE target and its emission reduction. This trend shows a potential progressive improvement for those countries to reduce their emission from the energy sector by 2040. With their current high base scenario, they may reach a higher target in the future to integrate variable RE to the APG and contributing to emission reduction in the region.
Examining the Impact of Excessive Daytime Sleepiness on Utility Scores in Patients with Obstructive Sleep Apnoea and/or Narcolepsy in Five European Countries
Authors: Cambron-Mellott M. Janelle , Mettam Sam , Li Vicky W. , Rowland John C. , Castro JeanPierre Coaquira 
Published: December 2021

Abstract
Background: Excessive daytime sleepiness (EDS) is a cardinal symptom of narcolepsy and affects many patients with obstructive sleep apnoea (OSA). EDS is associated with reduced quality of life, increased accident risk, and poor workplace performance. Given the impact of EDS, the ability to predict health-related utility from sleepiness is valuable for examining the cost effectiveness of novel treatments. The aim of this study was to examine the association between EDS and EQ-5D in patients with OSA and/or narcolepsy by modelling EQ-5D utility scores from Epworth Sleepiness Scale (ESS) scores.Methods: Data were obtained from the Europe 2016/2017 National Health and Wellness Survey, an online, general population survey, designed to represent the age and gender composition of each country’s adult population. Analyses included 2,348 patients self-reporting symptomatic and diagnosed OSA (n=2,277), narcolepsy (n=48), or both (n=23). Multivariable models were used to examine ESS as a predictor of EQ-5D utility while adjusting for covariates of interest. Results were validated following the National Institute for Health and Care Excellence Decision Support Unit guidelines for predictive modeling.Results: Utility decreased as EDS severity increased (no EDS: 0.711±0.251, mild: 0.685±0.261, moderate: 0.643±0.268, severe: 0.559±0.323). Whereas participants with only OSA or only narcolepsy did not differ in utility, those with both conditions had lower scores (0.685±0.266 and 0.627±0.325 vs. 0.439±0.340, respectively). Piecewise linear regression identified a single breakpoint at ESS score of 11.29. In the final model, for each point increase in ESS score, the corresponding decrease in EQ-5D utility was larger among patients with ESS scores ≥12 compared to patients with ESS scores ≤11 (model slopes: -0.0131 vs. -0.0026, respectively). Findings from the validation sample confirmed these results.Conclusions: This study demonstrates the impact of sleepiness on quality of life (QoL) and its negative impact irrespective of sleep condition (OSA or narcolepsy). The breakpoint identified is relatively consistent with the established ESS cutoff score ≥11, which demarcates pathological sleepiness. Furthermore, as EDS severity worsens (increases) on the ESS, the impact on QoL is greater.