bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nuclear translocation of p85β promotes tumorigenesis of PIK3CA helical domain mutant cancer
Authors: Hao Yujun , He Baoyu , Wu Liping , Li Yamu , Wang Chao , Wang Ting , Sun Longci , Zhang Yanhua , Zhan Yangyang , Zhao Yiqing , Markowitz Sanford , Veigl Martina , Conlon Ronald , Wang Zhenghe 
Published: May 2021

Abstract
PI3Ks consist of p110 catalytic subunits and p85 regulatory subunits. PIK3CA, encoding p110, is frequently mutated in human cancers. Most PIK3CA mutations are clustered in the helical domain or the kinase domain. Here, we report that p85 disassociates from p110α helical domain mutant protein and translocates into the nucleus through a nuclear localization sequence (NLS). Nuclear p85β recruits deubiquitinase USP7 to stabilize EZH1 and EZH2 and enhances H3K27 trimethylation. Knockout of p85β or p85β NLS mutant reduces the growth of tumors harboring a PIK3CA helical domain mutation. Our studies illuminate a novel mechanism by which PIK3CA helical domain mutations exert their oncogenic function. Finally, a combination of Alpelisib, a p110α-specific inhibitor, and an EZH inhibitor, Tazemetostat, induces regression of xenograft tumors harboring a PIK3CA helical domain mutation, but not tumors with either a WT PIK3CA or a PIK3CA kinase domain mutation, suggesting that the drug combination could be an effective therapeutic approach for PIK3CA helical domain mutant tumors.
The Clinical Prediction Factors of Non Chronic Total Occlusion Lesions Progression in Patients Underwent Percutaneous Coronary Intervention for Chronic Total Occlusion Lesions
Authors: wang jian , He Song-yuan 
Published: May 2021

Abstract
Backgroud :To investigate the clinical prediction factors of non chronic total occlusion lesions progression in patients underwent percutaneous coronary intervention(PCI) for chronic total occlusion lesions.Methods: A total of 450 unstable angina patients (57.1 ± 9.2 years) underwent PCI from January 2016 to December 2018 in Beijing Anzhen Hospital were enrolled in this study. All patients underwent PCI as treatment for chronic total occlusion lesions. Clinical and angiographic follow-up were performed in 12 months. All patients were divided into non chronic total occlusion lesions(NCTOL) progression group (205 cases) and the control group (275 cases) according to angiographic follow-up outcome in 12 months. The clinical and angiographic features were analyzed.Results: levels of adenosine diphosphate (ADP) induced platelet aggregation rate(ADP-IPA) (51.89 ± 14.81 vs 39.63 ± 17.12，P <0.01), lipoprotein(a)(Lp(a))(0.22 ± 0.26 vs 0.14 ± 0.18,P < 0.05) in NCTOL progression group were significantly higher than those in the control group. Logistic regression showed that ADP induced PAR (odds ratio =1.047, 95% confidence interval:1.014-1.082, P = 0.005), Lp(a) (odds ratio =11.972, 95% confidence interval: 1.230 -116.570, P = 0.033) were independent predictors of NCTOL progression. Partial correlation analysis showed that ADP-IPA was positively correlated with NCTOL progression( r = 0. 351,P < 0. 001) .Receiver operating characteristic(ROC) curve showed that the boundary point of ADP-IPA to predict NCTOL progression was 30%, the sensitivity was 86.2% and the specificity was 68.9%.Conclusions: ADP-IPA may be an valuable predictor for NCTOL progression .in unstable angina patients underwent percutaneous coronary intervention(PCI) for chronic total occlusion lesions.
The Expression of Netrin-1 in the Osteoarthritic Temporomandibular Joint
Authors: Xiao Mian , Hu Zhihui , Jiang Henghua , Li Cheng , Guo Huilin , Fang Wei , Long Xing 
Published: May 2021

Abstract
Subchondral bone degeneration is the main pathological change during temporomandibular joint (TMJ) osteoarthritis (OA) development. Netrin-1, an axon-guiding factor, might play roles in OA development and pain. The purpose of this study was to investigate the expression of Netrin-1 in TMJ OA and its possible role in the progression of TMJ OA and pain. The content of Netrin-1 in the synovial fluid of temporomandibular joint disorders (TMDs) patients was detected by ELISA. After injection of MIA into the TMJ animal model, hematoxylin & eosin (H&E) staining, toluidine blue (TB) staining and micro-CT were performed to detect the change of TMJ. Netrin-1 expression in the condyle was detected by immunohistochemical (IHC) staining. The pain experience was examined by the von Frey test in animal model. The concentration of Netrin-1 increased in the synovial fluid of TMJ OA patients with the VAS scores increased. In the TMJ OA model, the structural disorder of subchondral bone was the most obvious at the 2nd week. In addition, the head withdrawal threshold (HWT) was significantly decreased in the TMJ OA model. Netrin-1 expression increased in the subchondral bone at the 2nd week after MIA injection in the mouse TMJ. Cultivate raw264.7 cells and induce them to differentiate into osteoclasts. Netrin-1 and its receptor Unc5B are detected to be expressed on the osteoclast membrane. Thus, Netrin-1 might be a regulator during degeneration and pain in the process of TMJ OA.
Job Performance of Medical Graduates with Compulsory Services in Underserved Rural Areas in China: A Cohort Study
Authors: Li Mingyue , Wang Ziyue , Zhang Baisong , Wei Tiantian , Hu Dan , Liu Xiaoyun 
Published: May 2021

Abstract
Objective China started a national program in 2010 to train qualified general practitioners with compulsory services in rural and remote areas. While this compulsory services program (CSP) has shown positive effects on staffing primary health care in rural areas, very little is known about how well they perform in the rural service. This study aims to evaluate the job performance of those medical graduates from this program and how the program design has influenced their job performance. Methods A cohort study was conducted with medical graduates from CSP and non-CSP (NCSP) in four medical universities in central and western China. Baseline survey and three waves of follow-up surveys were conducted from 2015-2020. The pass rate of China National Medical Licensing Examinations (NMLE) and self-reported job performance were used as measurements of job performance. Comparisons were made between CSP and NCSP graduates. Multivariable regressions were used to identify factors affecting job performance. Results 2154 medical graduates were included in the sample, with 1586 CSP graduates and 568 NCSP graduates. CSP (90.6%) and NCSP (87.5%) graduates showed no difference in passing the NMLE (P=0.153). CSP graduates reported high job performance, similar to those NCSP graduates (CSP, 63.7; NCSP, 64.2). In the design of CSP, having officially budget posts improved job performance of CSP (β coefficient=4.87, P＜0.05). Working in hometown was also a significant factor that increase job performance when controlling the differences in contracting strategy (β coefficient=1.48, P＜0.05). Conclusion Medical students trained by CSP have demonstrated good job performance in primary healthcare systems in China. Compared to NCSP peers who work in urban areas in majority, CSP graduates’ high job performance could increase the accessibility of equal- or high-quality services in rural areas, which contributes to qualified workforce supply and health equity. Providing officially budgeted posts and working in hometowns can affect job performance and future retention. Early career support can have critical importance for CSP graduates.
Exploring Electroencephalography with the Aid of Quantum Mechanics
Authors: Popiel Nicholas J. M. , Metrow Colin , Laforge Geoffrey , Owen Adrian M. , Stojanoski Bobby , Soddu Andrea 
Published: May 2021

Abstract
An outstanding issue in cognitive neuroscience concerns how the brain is organized across different conditions. For instance, during the resting-state condition, the brain can be clustered into reliable and reproducible networks (e.g., sensory, default, executive networks). Interestingly, the same networks emerge during active conditions in response to various tasks. If similar patterns of neural activity have been found across diverse conditions, and therefore, different underlying processes and experiences of the environment, is the brain organized by a fundamental organizational principle? To test this, we applied principles of quantum mechanisms to model electroencephalogram (EEG) data. We uncovered a tendency for EEG signals to be localized in anterior regions of the brain during “rest”, and more uniformly distributed while engaged in a task (i.e., watching a movie). Moreover, we found analogous values to the Heisenberg uncertainty principle, suggesting a common underlying architecture of human brain activity in resting and task conditions. This underlying architecture manifests itself in the novel constant KBrain, which is extracted from the brain state with the least uncertainty. We would like to state that we are using the mathematics of quantum mechanics, but not claiming that the brain behaves as a quantum object.
Cadmium-induced Oxidative Stress in Meretrix Meretrix Gills Leads to Mitochondria-mediated Apoptosis
Authors: Wang Jinhua , Deng Wanfei , Zhou Ting , Bai Binbin , Chang Alan K. , Ying Xueping 
Published: May 2021

Abstract
Cadmium (Cd) is one of the most important marine environmental pollutants that can cause oxidative damage and apoptosis in living organisms, and mitochondria are the key target cell organelles of Cd toxicity. In this study, we investigated the effect of Cd on the mitochondria of Meretrix meretrix gill cells and the underlying mechanism of mitochondria-mediated apoptosis following exposure to the metal. Exposure of the clams to 1.5, 3, 6 and 12 mg L−1 Cd2+ solutions led to swollen mitochondria compared with the untreated clams. The mitochondria also became vacuolated at the higher Cd2+ concentrations. Biochemical assays showed that monoamine oxidase (MAO) activity and mitochondrial membrane potential (Δψm) increased at 1.5 mg L−1 Cd2+, but decreased at higher Cd2+ concentrations, while the activities of malate dehydrogenase (MDH) and cytochrome oxidase (CCO) and the scavenging capacities of anti-superoxide anion (ASA) and anti-hydroxy radical (AHR) all decreased with increasing Cd2+ concentrations. Significant increases in the levels of MDA and H2O2 as well as in the activity levels of caspase-3, -8, and -9 were also observed in the Cd2+-treated clams. The results implied that Cd might induce apoptosis in M. meretrix via the mitochondrial caspase-dependent pathway.
Early Knee Osteoarthritis Classification and Clinical Evolution: a Longitudinal Observational Study.
Authors: Alabajos-Cea Ana , Herrero-Manley Luz , Suso-Martí Luis , Pérez-Barquero Juan Alonso , Viosca-Herrero Enrique 
Published: May 2021

Abstract
Objective: The main objective was to determine the relevance of the diagnosis of early osteoarthritis (EOA) according to the existing criteria. The secondary objective was to evaluate the clinical progression of healthy subjects (HS) at risk for osteoarthritis and with EOA. Methods: A cross-sectional longitudinal study was performed. 105 participants were classified through difference diagnosis criteria as EOA patients or HS. Measures of disability, pain and disability self-reported variables were assessed. Two follow-ups were performed, reclassifying all the participants to assess their diagnosis and radiological progression, and evaluating the clinical progression by the self-reported measures.Results: Following the current diagnostic criteria the participants were divided as EOA (n=54) and HS (n=51). Most of the participants did not present changes in their classification, although some subjects were reclassified as EOA or HS in the follow-ups performed. In relation to clinical progression, the ANOVA did not reveal statistically significant differences in time for pain, disability, or psychological variables neither in the HS nor in the EOA.Conclusion: Current classification criteria for EOA based on self-reported measures could, make it difficult to clearly diagnose of EOA leading to changes in the classification of patients according to their condition at each particular moment.
coreSCD: Multi-Stakeholder Consensus on Core Outcomes for Sickle Cell Disease Clinical Trials
Authors: Tambor Ellen , Robinson Matoya , Hsu Lewis , Chang Hsing-Yuan , Naber Jennifer Al 
Published: May 2021

Abstract
BackgroundWith the dramatic increase in the pipeline for new sickle cell disease (SCD) therapies in recent years, the time is ripe to ensure a robust body of evidence is available for decision making by regulators, payers, clinicians, and patients. Harmonization of the outcomes selected across interventional trials enables optimal post-trial appraisal and decision making through valid pooled analyses and indirect comparisons. We employed a structured, multi-stakeholder consensus process to develop core outcome sets (COS) for use in clinical trials of SCD interventions.MethodsCoreSCD utilized a modified Delphi method adapted from the standards recommended by the Core Outcome Measures in Effectiveness Trials (COMET) Initiative. An initial list of candidate outcomes was developed through a targeted literature review and input from an 11-member advisory committee. A 44-member multi-stakeholder Delphi Panel was established and included patients and family members, advocates, clinicians, researchers, payers, health technology assessors, representatives from government agencies, and industry representatives. Patients/advocates comprised 25% of the Delphi Panel and orientation and training was provided prior to the consensus process to ensure all were prepared to participate meaningfully. Panelists completed three rounds of an online survey to rate the importance of candidate outcomes for inclusion in the COS. Summary data was provided between each voting round and an in-person consensus meeting was held between the second and third round of voting. Consensus rules were applied following each round of voting to eliminate outcomes that did not meet predetermined criteria for retention.ResultsConsensus was reached for two core outcome sets. The final COS for trials of disease-modifying therapies includes ten outcomes and the COS for trials of acute interventions includes six outcomes. Both core sets include clinical outcomes as well as outcomes related to functioning/quality of life, resource utilization, and survival/mortality.ConclusionsUse of the COS in clinical development programs for SCD will help to ensure that relevant, consistent outcomes are available for decision making across the product lifecycle.
Effect of Fly Ash on Setting Mechanism and Strength of Commercial Cement: A Chemical Approach
Authors: Bhuvana G. L. , Sherikar B. N. , Honnavar G.V. , Madhusudhana R. , Sahoo Balaram 
Published: May 2021

Abstract
The chemistry and mechanism of mechanical strength-development at different setting-times in different weight-ratios of proclaimed commercial-cement and fly-ash mixture is studied. The main content of fly-ash is the quartz (SiO2). According to our results, as the setting time increases, the quartz present in fly-ash gets utilized during setting of the cement to form the well known C-S-H gel (3CaO.2SiO2.3H2O). Our analysis suggests that the addition of fly-ash reduces the water requirement for the hydration-process. Furthermore, the fly-ash inhibits the formation of CaCO3 phase from portlandite (Ca(OH)2) through atmospheric CO2, and more importantly, it promotes the transformation of portlandite to form the C-S-H network which provides strength and long term stability to the set cement. As the commercial cement already contains optimum amount of fly-ash, any further addition of fly ash leaves the fly-ash partially unreacted which drastically decreases the compressive strength.
Influence of Al2O3 Content on Mechanical Properties of Silica-based Ceramic Cores Prepared by Stereolithography
Authors: Zheng Wen , Wu Jia-Min , Chen Shuang , Wang Chang-shun , Liu Chun-Lei , Hua Shuai-Bin , Yu Kang-Bo , Zhang Jie , Zhang Jing-Xian , Shi Yu-Sheng 
Published: May 2021

Abstract
Silica ceramic cores have played an important role in the manufacture of hollow blades due to its excellent chemical stability and moderate high-temperature mechanical properties. In this study, silica-based ceramics were prepared by stereolithography and the influence of Al2O3 content on mechanical properties of the silica-based ceramics was investigated. With the increase of Al2O3 content, the linear shrinkage of the silica-based ceramics first decreased and then increased, while the room-temperature flexural strength and the high-temperature flexural strength first increased and then decreased. As the Al2O3 content increased to 1.0 vol.%, the linear shrinkage was reduced to 1.64% because of the blocked viscous flow. Meanwhile, the room-temperature flexural strength and the high-temperature flexural strength were respectively improved to 20.38 MPa and 21.43 MPa with 1.0 vol.% Al2O3 due to the increased α-cristobalite and β-cristobalite content. Therefore, using the optimal content of Al2O3 in silica-based ceramics can provide excellent mechanical properties and ensure the reliability of silica-based ceramic cores for manufacturing hollow blades.
Synthesis of Bismuth Doped Yttria Stabilized Zirconia Electrolyte and Study of Ionic Conductivity
Authors: Guo Xia , Zhao Xiaobing , Liu Jinrong , He Weiyan 
Published: May 2021

Abstract
x%molBi3+-doped yttria-stabilized zirconia with 4%molYO1.5 (x = 0–5,BiYSZ) are prepared via lamellar liquid crystal template method.The influence of different doping amount of Bi3+ on crystal form,morphology,the ionic conductivity are investigated in detail.In addition,densification time of BiYSZ are determined.X-ray diffraction(XRD),Raman spectrum,Scanning Electron Microscope(SEM) results show that BiYSZ powder with stable tetragonal phase and spherical structure is nanometer level.Moreover,by using the Ac impedance spectroscopy to analyse conductivity of solid electrolytes,we find that Bi3+-doped yttria-stabilized zirconia with 4%molYO1.5 improve the ionic conductivity.Comparing all the compositions,3mol%Bi3+ doped yttria stabilized zirconia with 4%molY3+ gives the highest ionic conductivity of 7.41×10− 5 S/cm− 1 at 500℃,and sintering temperatures of BiYSZ reduce around 100℃ than Y0.04Zr0.96O2(4YSZ),ionic conductivity increases one order of magnitude.
Living with chronic headaches: A qualitative study from an outpatient pain clinic in Norway
Authors: Hervik Jill Brook , Foss Eva B. , Stub Trine 
Published: May 2021

Abstract
Chronic headaches are poorly managed in primary care despite a high level of morbidity. The aim of this study was to gain subjective information regarding the lives of chronic headache sufferers.MethodThis focused ethnography draws from in-depth, semi-structured interviews conducted with 16 patients who suffered from chronic headaches. Five main domains were explored in the data analysis: emotions related to headaches; trauma/stressful events; headache as a driver of behaviour; family bonding and coping mechanisms. Headache as a driver of behaviour had three subdomains: shame; loss of identity and lack of freedom.ResultsParticipants reported that pain restricted their lives in many ways. Issues included not being able to work full time and different levels of dependency on disability pension. The majority believed that trauma was the reason for their headaches. Shame and loss of identity appeared to be strongly associated with chronic pain. ConclusionThis study demonstrates that chronic headaches restrict sufferers’ lives, resulting in emotional and behavioural changes. Traumatic events of varying degrees throughout the course of life can initiate and maintain symptoms, which may become chronic and thereby have socio economic consequences, for individuals and society in general. Clinicians need to have an increased awareness as to the complexity of chronic headaches.PerspectiveThis article presents information regarding the lives of chronic headache sufferers. The findings suggests that these patients need a multidisciplinary treatment approach
Regional Cerebral Gray Matter Atrophy Is Associated With Cognitive Impairment in Hemodialysis Patients: a Cross-sectional and Longitudinal Voxel-based Morphological Mri Study
Authors: Wang Huiying , Huang Lixiang , Wu Gemuer , Li Jinping , Liu Lei , Zhang Tong , Zhu Jinxia , Zhang Xianchang , Shen Wen , Chai Chao , Xia Shuang 
Published: May 2021

Abstract
To explore changes of cerebral gray matter volumes (GMV) in hemodialysis patients, the clinical risk factors for GMV changes, and the relationship between GMV changes and neuropsychological tests results. Eighty-eight hemodialysis patients and seventy-six healthy controls (HCs) were recruited in this study. Fifty patients underwent follow-up magnetic resonance, blood biochemical examinations, and neuropsychological test (1.75±0.55 years). Changes in GMV between patients and HCs, longitudinal GMV changes in patients were explored. The clinical risk factors for the longitudinal GMV changes, the correlations between longitudinal GMV changes and neuropsychological tests changes in hemodialysis patients were analyzed. Compared to HCs, the hemodialysis patients had diffusely decreased in GMV (with age, sex, and total intracranial volume [TIV] as covariates, P<0.001, voxel-wise threshold false discovery rate [FDR] corrected). Compared with patients at baseline, regional decreased GMV were found in patients at follow-up (with age, and TIV as covariates, P<0.05, voxel-wise threshold FDR corrected). Increased serum urea, parathyroid hormone levels, and hemodialysis duration were independent risk factors for decreased GMV in hemodialysis patients (all P<0.05, FDR corrected). Hemodialysis patients had lower MMSE (27[26, 29]) and MoCA (22[19.48, 24.04]) scores than HCs (30[29, 30] and 28[26.89, 29]) (all P<0.05). The MMSE scores of hemodialysis patients at follow-up (26[25, 28.5]) were lower than those of patients at baseline (28[25, 29.5]) (P=0.02). The decreased left caudate volumes were positively correlated with reduced MMSE scores in hemodialysis patients (rs=0.437, P=0.033). Hemodialysis patients had diffused GM atrophy over time, which was related to cognitive impairment.
Polymethylmethacrylate-augmented Cannulated Pedicle Screw Fixation for High-energy Vertebral Compression Fracture With Osteoporosis
Authors: Liu Yao-yao , Xiao Jun , Yin Xiang , Liu Ming-Yong , Wang Zhong , He Lei , Liu Peng , Dai Fei 
Published: May 2021

Abstract
Background: High-energy vertebral compression fracture (HVCFs) with osteoporosis has higher requirement for the stability of pedicle screw internal fixation system. However, few studies have involved the clinical outcome of cannulated pedicle screw to augment fixation with polymethylmethacrylate (PMMA) under this condition. This study aims to investigate the mid-term efficacy of bone cement-injectable cannulated pedicle screw (CICPS) in HVCFs with osteoporosis.Methods: Eighteen patients with HVCFs (T < -2.5) were underwent spinal fixation by CICPS from 2012 to 2017. The operation time, blood loss, and hospitalization time were recorded. Pain and functional recovery were evaluated by Visual Analog Scale VAS) and Oswestry Disability Index (ODI), respectively. X-ray films were taken to evaluate the loss of vertebral height, kyphosis angle, pedicle screw loosening, and bony fusion. Surgical related complications were also recorded.Results: The average follow-up time was 18.5 ± 8.7 months (range, 6-54 months). VAS and ODI scores indicated significant improvements in postoperative pain and activity function (P < 0.05). Comparing the last follow-up with the postoperative imaging findings, the loss of vertebral height and kyphosis angle was 3.4 ± 1.2 mm and 7.8 ± 3.8°, respectively. The rate of bone graft fusion was 100% while no cases were involved in screw loosening or extraction. 1 case of superficial infection, 2 cases of PMMA leakage, and 1 case of cerebrospinal fluid leakage were found.Conclusions: CICPS fixation using PMMA augmentation may suggest as a feasible surgical technique in osteoporotic patients with HVCFs.