bluuebunny/crossref_metadata_2025_split huggingface dataset:
USF1 Transcriptionally Regulates UGT1A3 and Promotes Lung Adenocarcinoma Progression by Regulating Neurotrophin Signaling Pathway
Authors: Wang Yu , Zhao Yun-Xia , Zhang Xiang-Wei , Jiang Yuan-Zhu , Ma Wei , Zhang Lin , Dong Wei 
Published: January 2022

Background: Lung cancer remains the leading cause of oncological death. There is an urgent need to discover new molecular targets and to develop new treatments. Our previous study showed that one of the UDP-glucuronosyltransferases (UGTs) family, UGT1A3, is an important prognostic factor for lung adenocarcinoma (LUAD), inhibiting UGT1A3 could significantly improve the efficacy of anti-tumor drugs. In this study, we aimed to explore the upstream transcriptional factor (USF1) of UGT1A3 and its way of playing a role in LUAD.Methods: The UGT1A3 promoter region was analyzed and dual-luciferase assay was involved to explore whether USF1 could bind to this region, and the possible regulation effects of USF1 to UGT1A3 was indicated by siRNA and recovery experiment. Then, the Cancer Genome Atlas database was used to analyze USF1 clinical features. The expression level of USF1 was detected by immunohistochemical assay and Western blotting. Cellular viability, proliferation, migration and invasion potential were also investigated. Meanwhile, the effect of USF1 in LUAD progression was detected in a mouse model. The downstream signaling pathway was analyzed by bioinformatic analysis and the expression of all related proteins was detected.Results: UGT1A3 was transcriptionally regulated by USF1, which was highly expressed in all investigated samples including patients’ tissues, studied cells lines, and mouse models. The knockdown of USF1 inhibited cells viability, proliferation, migration and invasion, and reduced the tumor volume. Moreover, USF1 promoted the progress of LUAD by regulating the neurotrophin signaling pathway.Conclusion: As an important transcriptional regulator of UGT1A3, USF1 was highly expressed in LUAD and promoted LUAD progression by regulating the neurotrophin signaling pathway. These findings provide a new theoretical data that could serve as a good foundation for the treatment of LUAD.
Random and Systematic Variation in Nanoscale Hf0.5Zr0.5O2 Ferroelectric FinFETs: Physical Origin and Neuromorphic Circuit Implications
Authors: De Sourav , Baig Md. Aftab , Qiu Bo-Han , Müller Franz , Le Hoang-Hiep , Lederer Maximilian , Kämpfe Thomas , Ali Tarek , Sung Po-Jung , Su Chun-Jung , Lee Yao-Jen , Lu Darsen D. 
Published: January 2022

This work presents 2-bits/cell operation in deeply scaled ferroelectric finFETs (Fe-finFET) with a 1 µs write pulse of maximum ±5 V amplitude and WRITE endurance above 109 cycles. Fe-finFET devices with single and multiple fins have been fabricated on an SOI wafer using a gate first process, with gate lengths down to 70 nm and fin width 20 nm. Extrapolated retention above 10 years also ensures stable inference operation for 10 years without any need for re-training. Statistical modeling of device-to-device and cycle-to-cycle variation is performed based on measured data and applied to neural network simulations using the CIMulator software platform. Stochastic device-to-device variation is mainly compensated during online training and has virtually no impact on training accuracy. On the other hand, stochastic cycle-to-cycle threshold voltage variation up to 400 mV can be tolerated for MNIST handwritten digits recognition. A substantial inference accuracy drop with systematic retention degradation was observed in analog neural networks. However, quaternary neural networks (QNNs) and binary neural networks (BNNs) with Fe-finFETs as synaptic devices demonstrated excellent immunity toward the cumulative impact of stochastic and systematic variations.
Efficacy and Toxicity of Whole Pelvic Radiotherapy Versus Prostate-Only Radiotherapy in Localized Prostate Cancer: A Systematic Review and Meta-Analysis
Authors: Wang Shilin , Tang Wen , Luo Huanli , Jin Fu , Wang Ying 
Published: January 2022

BackgroundThere is little level 1 evidence regarding the relative efficacy and toxicity of whole pelvic radiotherapy (WPRT) compared with prostate-only radiotherapy (PORT) for localized prostate cancer.MethodsWe used Cochrane, PubMed, Embase, Medline databases, and ClinicalTrials.gov to systematically search for all relevant clinical studies. The data on efficacy and toxicity were extracted for quality assessment and meta-analysis to quantify the effect of WPRT on biochemical failure-free survival (BFFS), progression-free survival (PFS), distant metastasis-free survival (DMFS), overall survival (OS), gastrointestinal (GI) toxicity, and genitourinary (GU) toxicity compared with PORT. The review is registered on PROSPERO, number: CRD42021254752.ResultsThe results revealed that compared with PORT, WPRT significantly improved 5-year BFFS and PFS, and it was irrelevant to whether the patients had undergone radical prostatectomy (RP). In addition, for the patients who did not receive RP, the 5-year DMFS of WPRT was better than that of PORT. However, WPRT significantly increased not only the grade 2 or worse (G2+) acute GI toxicity of non-RP studies and RP studies, but also the G2+ late GI toxicity of non-RP studies. Subgroup analysis of non-RP studies found that, when the pelvic radiation dose was &gt;49 Gy (equivalent-doses-in-2-Gy-fractions, EQD-2), WPRT was more beneficial to PFS than PORT, but significantly increased the risk of G2+ acute and late GU toxicity.ConclusionsMeta-analysis demonstrates that WPRT can significantly improve BFFS and PFS for localized prostate cancer than PORT, but the increased risk of G2+ acute and late GI toxicity must be considered.Systematic Review RegistrationPROSPERO CRD42021254752.
How Can a High-Performance Screening Strategy Be Determined for Cervical Cancer Prevention? Evidence From a Hierarchical Clustering Analysis of a Multicentric Clinical Study
Authors: Bao Heling , Zhang Xiaosong , Bi Hui , Zhao Yun , Fang Liwen , Wang Haijun , Wang Linhong 
Published: January 2022

BackgroundThis study aimed to explore the cluster patterns of cervical cancer screening strategies for detecting high-grade precancerous lesions in terms of benefits, costs, and efficiency.MethodsA total of 2,065 referral women aged 25–64 years were recruited and underwent human papillomavirus (HPV) testing, liquid-based cytology with manual reading, and cytology with artificial intelligence (AI)-assisted reading. All women were assessed by colposcopy and histological examination. We formed 14 screening strategies based on primary cytology screening, primary HPV screening incorporating HPV-16/18 genotyping triage, cytology triage, or both, and co-testing. The primary outcomes were cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and grade 3 or worse (CIN3+). The hierarchical clustering method was applied to multifaceted indicators, and then, the resulting clusters were described in terms of benefits, costs, efficiency, and their interaction. This study was registered (No. ChiCTR2000034131).ResultsThe relative sensitivity of HPV-based strategies compared with cytology alone with the threshold of LSIL+ ranged from 0.68 to 1.19 for CIN2+ detection and from 0.72 to 1.11 for CIN3+ detection, whereas the relative specificity ranged from 0.55 to 1.43 for CIN2+ detection and from 0.51 to 1.51 for CIN3+ detection. Five significant clusters according to the trade-off among benefits, costs, and efficiency were identified. The cluster including four primary HPV screening strategies showed the optimal balance. HPV testing with HPV-16/18 genotyping and AI-based cytology triage presented the optimal trade-off for CIN3+ detection relative to cytology alone in terms of relative sensitivity (1.06), relative specificity (0.72), colposcopies for 1 CIN3+ (3.7 vs. 3.1), a load of follow-up for women with HPV-positive and normal cytology (7.0% vs. 22.3%), and the work of manual cytology reading (35.1% vs. 100%).ConclusionsOur study provided clinical and methodological evidence on the choice of HPV-based screening strategies. The cluster including primary HPV screening with genotyping and cytology triage showed an optimal balance among benefit, cost, and efficiency.
Predictors of Spontaneous Rupture of Hepatocellular Carcinoma and Clinical Outcomes Following Hepatectomy
Authors: Chen Yiran , Guo Deliang , Li Xinyi , Xu Chang , Zhu Qian 
Published: January 2022

ObjectiveTo explore the independent predictive factors of spontaneous tumor rupture (STR) in patients undergoing curative resection of hepatocellular carcinoma (HCC), and to evaluate the impact of STRHCC on long-term survival after hepatectomy.MethodsThe clinicopathological parameters of 106 patients with STRHCC and 201 patients with non-ruptured HCC who underwent hepatectomy from January 2007 to November 2011 at the Eastern Hepatobiliary Surgery Hospital and Zhongnan Hospital of Wuhan University were analyzed using propensity score matching (PSM) and a logistic regression model.ResultsFactors including hypertension, cirrhosis, total bilirubin (TB), tumor size, and ascites were independent predictors of STR. For all 307 HCC patients, the 1-, 3- and 5-year overall survival (OS) rates were 54.0%, 37.3% and 33.8%, respectively. After PSM, the 1-, 3-, and 5-year OS rates in the ruptured group remained significantly lower at 41.5%, 23.5%, and 17.5% when compared with the non-ruptured group at 70.8%, 47.1%, and 37.6%, respectively, while the 1-, 3-, and 5-year disease-free survival (DFS) rates between the groups did not differ significantly (50.4%, 35.1%, 27.1% vs 55.4%, 38.2%, 27.4%). STRHCC was significantly associated with increased risk of OS, but not of shorter DFS. No significant difference in postoperative morbidity or hospital death was observed between the groups.ConclusionFactors including hypertension, liver cirrhosis, higher TB levels, tumor size &gt; 5cm, and ascites are significant predictors of STR. The recurrence rate of patients in the ruptured group was significantly higher than that of patients in the non-ruptured group. STR results in poorer OS but not DFS in patients undergoing curative resection for HCC. STRHCC has no impact on postoperative morbidity and mortality after hepatectomy.
Development of the ICF-CY Set for Cardiac Rehabilitation After Pediatric Congenital Heart Surgery
Authors: Luo Wen-Yi , Ni Ping , Chen Lin , Pan Qian-Qian , Zhang Hao , Zhang Ya-Qing 
Published: January 2022

BackgroundMost children with congenital heart disease (CHD) require surgical repair, and postoperative rehabilitation is an essential step to restore the quality of life. The present study constructs and confirms the International Classification of Functioning, Disability, and Health for Children and Youth core set for children with congenital heart disease 1 year after surgery (ICF-CY-CHDS).MethodsFrom February 2021 to August 2021, 340 children aged 3–6 years after CHD surgery were evaluated using the ICF-CY-CHDS and analyzed using the Rasch model.ResultsThe final ICF-CY-CHDS contained 22 categories; it exhibited a nonsignificant χ2 test result for the item-trait interaction (χ2 = 6736.37, p = 0.8660, Bonferroni-adjusted p = 0.0023). The average severity of children was less than the average difficulty of categories (−2.26 logit &lt;0 logit). The weighted k of all the categories was 0.964 (p &lt; 0.001), and the item separation index was 0.96. The area under the ROC curve of children with a diagnosis result of heart failure was 0.866 (95% CI: 0.801 ~0.931) with good sensitivity (0.875) and specificity (0.759).ConclusionThe ICF-CY-CHDS presents a preliminary practical direction during early cardiac rehabilitation after pediatric CHD surgery, and thus provides a basis and scope for clinical evaluation and intervention program formulation.
Transmembrane 4 L Six Family Member 1 Suppresses Hormone Receptor-–Positive, HER2-Negative Breast Cancer Cell Proliferation
Authors: Chen Jie , Zhu Jin , Xu Shuai-Jun , Zhou Jun , Ding Xiao-Fei , Liang Yong , Chen Guang , Lu Hong-Sheng 
Published: January 2022

Background: The prognosis of breast cancer varies according to the molecular subtype. Transmembrane 4 L six family 1 (TM4SF1) exhibits different expression patterns among the molecular subtypes of breast cancer. However, the expression profile of TM4SF1 in hormone receptor HR+HER2- breast cancer remains unclear.Methods: TM4SF1 mRNA levels were examined in major subclasses of breast cancer by analyzing The Cancer Genome Atlas (TCGA) datasets. In addition, TM4SF1 protein and mRNA levels in HR+HER2- breast cancer tissue samples were determined by immunohistochemistry and Western blot assay. The effect of TM4SF1 on cell proliferation was evaluated using MTT, colony formation, 3D organoid, and xenograft models, following the TM4SF1 overexpression or knockdown.Results: TCGA database analysis demonstrated that TM4SF1 was downregulated in breast cancer compared with the healthy adjacent breast tissue. In addition, the expression of TM4SF1 in basal-like one and the mesenchymal TNBC tissue was higher than that of the healthy adjacent breast tissue. Other types, including the luminal androgen receptor–positive TNBC tissue, expressed lower levels of TM4SF1. Immunohistochemistry and real-time quantitative PCR assays demonstrated that the TM4SF1 protein and mRNA levels were downregulated in the HR+HER2- breast cancer tissue compared with the healthy adjacent tissue. Moreover, the TM4SF1 overexpression reduced the viability of MCF-7 and ZR-75-1 breast cancer cells, whilst reducing the number of colonies and 3D-organoids formed by these cell lines. By contrast, TM4SF1 knockdown led to an increased MCF-7 cell proliferation. However, in the TNBC cell line, MDA-MB-231, TM4SF1 silencing reduced cell proliferation. In vivo, the TM4SF1 overexpression inhibited MCF-7 xenograft growth in a nude mouse model, which was associated with the downregulation of the Ki-67 expression, apoptosis induction, and inhibition of the mTOR pathway.Conclusion: TM4SF1 is downregulated in HR + HER2-breast cancer, and the overexpression of TM4SF1 suppresses cell proliferation in this cancer subtype.
Integrative Metabolomics, Proteomics and Transcriptomics Analysis Reveals Liver Toxicity of Mesoporous Silica Nanoparticles
Authors: Li Jing , Sun Runbin , Xu Hui , Wang Guangji 
Published: January 2022

As pharmaceutical excipients, mesoporous silica nanoparticles (MSNs) have attracted considerable concern based on potential risks to the public. The impact of MSNs on biochemical metabolism is poorly understood, and few studies have compared the effects of MSNs administered via different routes. To evaluate the hepatotoxicity of MSNs, metabolomics, proteomics and transcriptomic analyses were performed in mice after intravenous (20 mg/kg/d) or oral ad-ministration (200 mg/kg/d) of MSNs for 10 days. Intravenous injection induced significant hepatic injury based on pathological inspection and increased the levels of AST/ALT and the inflammatory factors IL-6, IL-1β and TNF-a. Omics data suggested intravenous administration of MSNs perturbed the following metabolites: succinate, hypoxanthine, GSSG, NADP+, NADPH and 6-phosphogluconic acid. In addition, increases in GPX, SOD3, G6PD, HK, and PFK at proteomic and transcriptomic levels suggested elevation of glycolysis and pentose phosphate pathway, synthesis of glutathione and nucleotides, and antioxidative pathway activity, whereas oxidative phosphorylation, TCA and mitochondrial energy metabolism were reduced. On the other hand, oral administration of MSNs disturbed inflammatory factors and metabolites of ribose-5-phosphate, 6-phosphogluconate, GSSG, and NADP+ associated with the pentose phosphate pathway, glutathione synthesis and oxidative stress albeit to a lesser extent than intravenous injection despite the administration of a ten-fold greater dose. Overall, systematic biological data suggested that intravenous injection of nanoparticles of pharmaceutical excipients substantially affected hepatic metabolism function and induced oxidative stress and inflammation, whereas oral administration exhibited milder effects compared with intravenous injection.
Nursing Students’ Emotional State and Perceived Competence During the COVID-19 Pandemic: The Vital Role of Teacher and Peer Support
Authors: Utvær Britt Karin , Torbergsen Hanne , Paulsby Tove Engan , Haugan Gørill 
Published: January 2022

BackgroundThe COVID-19 pandemic has led to the shutdown of society and created sudden and long-lasting changes in teaching practices, forcing many nursing students to study remotely at home. These students’ relatedness with their teachers and peers has been limited and mainly online. Several studies have indicated that students’ emotional states and mental health have been negatively affected by the pandemic, representing a serious challenge for many countries. Because they use only digital tools, online students have perceived a decline in teacher and peer support. Likewise, these students have reported feelings of sadness, loneliness, anxiety, and stress, affecting their learning and competence development.AimsTo investigate the associations between peer support, teacher support, emotional state, and perceived competence in nursing students during the pandemic.MethodsThis cross-sectional study collected quantitative survey data from 329 nursing students at a large university in Norway. Structural equation modeling (SEM) was used to test seven associations among peer support, teacher support, emotional state, and perceived competence.ResultsTeacher support had a significant direct effect on perceived competence, while peer support almost had a significant direct effect. However, the emotional state was directly affected by peer support and had a direct impact on perceived competence. Hence, teacher and peer support is important to nursing students’ perceived competence.ConclusionDuring the COVID-19 pandemic, both peer and teacher support can significantly support students’ competence development. Therefore, students should utilize the support of their teachers and peers in a structured manner to bolster their competence development.
Mental Pain Surrounding Suicidal Behaviour: A Review of What Has Been Described and Clinical Recommendations for Help
Authors: Morales Susana , Barros Jorge 
Published: January 2022

ObjectiveTo conduct a comprehensive review of scientific publications related to mental pain and suicide risk in order to deepen relevant aspects to guide clinical interventions.MethodUsing a text analysis tool, we collected the terms most frequently linked with that situation in published results of research using various tools to evaluate mental pain or psychache.DiscussionWe propose clinical interventions for the clinical conditions most commonly associated with mental pain.
Estimating Child Mortality at the Sub-national Level in Papua New Guinea: Evidence From the Integrated Health and Demographic Surveillance System
Authors: Pham Bang Nguyen , Emori Rebecca Bogarobu , Ha Tam , Parrish Anne-Maree , Okely Anthony D. 
Published: January 2022

BackgroundChild mortality is an important indication of an effective public health system. Data sources available for the estimation of child mortality in Papua New Guinea (PNG) are limited.ObjectiveThe objective of this study was to provide child mortality estimates at the sub-national level in PNG using new data from the integrated Health and Demographic Surveillance System (iHDSS).MethodUsing direct estimation and indirect estimation methods, household vital statistics and maternal birth history data were analysed to estimate three key child health indicators: Under 5 Mortality Rate (U5MR), Infant Mortality Rate (IMR) and Neonatal Mortality Rate (NMR) for the period 2014–2017. Differentials of estimates were evaluated by comparing the mean relative differences between the two methods.ResultsThe direct estimations showed U5MR of 93, IMR of 51 and NMR of 34 per 1000 live births for all the sites in the period 2014–2017. The indirect estimations reported an U5MR of 105 and IMR of 67 per 1000 live births for all the sites in 2014. The mean relative differences in U5MR and IMR estimates between the two methods were 3 and 24 percentage points, respectively. U5MR estimates varied across the surveillance sites, with the highest level observed in Hela Province (136), and followed by Eastern Highlands (122), Madang (105), and Central (42).DiscussionThe indirect estimations showed higher estimates for U5MR and IMR than the direct estimations. The differentials between IMR estimates were larger than between U5MR estimates, implying the U5MR estimates are more reliable than IMR estimates. The variations in child mortality estimates between provinces highlight the impact of contextual factors on child mortality. The high U5MR estimates were likely associated with inequality in socioeconomic development, limited access to healthcare services, and a result of the measles outbreaks that occurred in the highlands region from 2014-2017.ConclusionThe iHDSS has provided reliable data for the direct and indirect estimations of child mortality at the sub-national level. This data source is complementary to the existing national data sources for monitoring and reporting child mortality in PNG.
DETERMINAN MANAJEMEN LABA PADA SEKTOR INDUSTRI BARANG KONSUMSI DI INDONESIA
Authors: Priharta Andry , Rustiana Siti Hamidah , Rahayu Dewi Puji , Maryati Maryati , Hadiansah Nur 
Published: January 2022

<p>This research aims to empirically prove whether free cash flow, leverage, institutional ownership and profitability affect earnings management. The research was conducted at manufacturing companies in the consumer goods industry sector listed on the Indonesia Stock Exchange (IDX) for the 2014-2018 period with a regression analysis of panel data fixed effects model. Through purposive sampling, there are 38 companies for the research and the results prove that partially, free cash flow has a significant negative effect, leverage has a significant positive effect, and profitability has a significant positive effect, while institutional ownership has a positive and insignificant effect. Simultaneously, all independent variables have a significant effect on earnings management with a determination coefficient of 96% while the remaining four percent is influenced by other factors.</p><p><strong>Keywords</strong> : Free cash flow, leverage, institutional ownership, profitability, earnings management</p>
Cell-Based Microfluidic Device Utilizing Cell Sheet Technology
Authors: Sakaguchi Katsuhisa , Akimoto Kei , Takaira Masanori , Tanaka Ryu-ichiro , Shimizu Tatsuya , Umezu Shinjiro 
Published: January 2022

The development of microelectromechanical systems has resulted in the rapid development of polydimethylpolysiloxane (PDMS) microfluidic devices for drug screening models. Various cell functions, such as the response of endothelial cells to fluids, have been elucidated using microfluidic devices. Additionally, organ-on-a-chip systems that include organs that are important for biological circulation, such as the heart, liver, pancreas, kidneys, and brain, have been developed. These organs realize the biological circulation system in a manner that cannot be reproduced by artificial organs; however, the flow channels between the organs are often artificially created by PDMS. In this study, we developed a microfluidic device consisting only of cells, by combining cell sheet technology with microtitanium wires. Microwires were placed between stacked fibroblast cell sheets, and the cell sheets adhered to each other, after which the microwires were removed leaving a luminal structure with a size approximately equal to the arteriolar size. The lumen structure was constructed using wires with diameters of 50, 100, 150, and 200
μ
m, which were approximations of the arteriole diameters. Furthermore, using a perfusion device, we successfully perfused the luminal structure created inside the cell sheets. The results revealed that a culture solution can be supplied to a cell sheet with a very high cell density. The biofabrication technology proposed in this study can contribute to the development of organ-on-a-chip systems.