bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrative proteomics reveals the role of E3 ubiquitin ligase SYVN1 in hepatocellular carcinoma metastasis
Authors: Ji Feiyang , Zhou Menghao , Sun Zeyu , Jiang Zhengyi , Zhu Huihui , Xie Zhongyang , Ouyang Xiaoxi , Zhang Lingjian , Li Lanjuan 
Published: July 2021

AbstractBackgroundTumor metastasis is a major factor for poor prognosis of hepatocellular carcinoma (HCC), but the relationship between ubiquitination and metastasis need to be studied more systematically. We analyzed the ubiquitinome of HCC in this study to have a more comprehensive insight into human HCC metastasis.MethodsThe protein ubiquitination levels in 15 HCC specimens with vascular invasion and 15 without vascular invasion were detected by ubiquitinome. Proteins with significantly different ubiquitination levels between HCCs with and without vascular invasion were used to predict E3 ubiquitin ligases associated with tumor metastasis. The topological network of protein substrates and corresponding E3 ubiquitin ligases was constructed to identify the key E3 ubiquitin ligase. Besides, the growth, migration and invasion ability of LM3 and HUH7 hepatoma cell lines with and without SYVN1 expression interference were measured by cell proliferation assay, subcutaneous tumor assay, umphal vein endothelium tube formation assay, transwell migration and invasion assays. Finally, the interacting proteins of SYVN1 were screened and verified by protein interaction omics, immunofluorescence, and immunoprecipitation. Ubiquitin levels of related protein substrates in LM3 and HUH7 cells were compared in negative control, SYVN1 knockdown, and SYVN1 overexpression groups.ResultsIn this study, our whole‐cell proteomic dataset and ubiquitinomic dataset contained approximately 5600 proteins and 12,000 ubiquitinated sites. We discovered increased ubiquitinated sites with shorter ubiquitin chains during the progression of HCC metastasis. In addition, proteomic and ubiquitinomic analyses revealed that high expression of E3 ubiquitin‐protein ligase SYVN1 is related with tumor metastasis. Furthermore, we found that SYVN1 interacted with heat shock protein 90 (HSP90) and impacted the ubiquitination of eukaryotic elongation factor 2 kinase (EEF2K).ConclusionsThe ubiquitination profiles of HCC with and without vascular invasion were significantly different. SYVN1 was the most important E3 ubiquitin‐protein ligase responsible for this phenomenon, and it was related with tumor metastasis and growth. Therefore, SYVN1 might be a potential therapeutic target for HCC.
Long non‐coding RNA HULC stimulates the epithelial–mesenchymal transition process and vasculogenic mimicry in human glioblastoma
Authors: Yin Tiantian , Wu Jing , Hu Yuchen , Zhang Min , He Jie 
Published: July 2021

AbstractBackgroundLong non‐coding RNA (lncRNA) HULC (highly upregulated in liver cancer) is considered as an oncogenic factor for various malignant tumors. This study aimed to reveal the role of lncRNA HULC in the malignant behavior of glioblastoma (GBM) by exploring its effects on the epithelial–mesenchymal transition (EMT) and vasculogenic mimicry (VM) of human GBM.Materials and MethodsThe contents of VM in 27 GBM samples were assessed by immunohistochemistry‐histology and their association with progress‐free survival (PFS) was analyzed. Human GBM SHG44 and U87 cells were manipulated to establish stable lncRNA HULC overexpressing and silencing cells by lentivirus‐based technology. The effects of altered lncRNA HULC on vasculogenic tubular formation, invasion, and EMT process in GBM cells were tested in vitro and the growth of implanted GBM tumors and their EMT process were examined in vivo.ResultsThe numbers of VM were positively associated with disease progression, but negatively with PFS periods of GBM patients. Compared with the control vec cells, lncRNA HULC overexpression significantly increased the tubular formation, invasion, and EMT process of both SHG44 and U87 cells, accompanied by promoting the growth of implanted GBM tumors and EMT process in mice. LncRNA HULC silencing had opposite effects on the tubular formation, invasion, and EMT process as well as tumor growth of GBM cells.ConclusionLncRNA HULC stimulates the EMT process and VM in human GBM, and may be a therapeutic target for intervention of GBM.
A Body Shape Index (ABSI), hip index, and risk of cancer in the UK Biobank cohort
Authors: Christakoudi Sofia , Tsilidis Konstantinos K. , Evangelou Evangelos , Riboli Elio 
Published: July 2021

AbstractAbdominal size is associated positively with the risk of some cancers but the influence of body mass index (BMI) and gluteofemoral size is unclear because waist and hip circumference are strongly correlated with BMI. We examined associations of 33 cancers with A Body Shape Index (ABSI) and hip index (HI), which are independent of BMI by design, and compared these with waist and hip circumference, using multivariable Cox proportional hazards models in UK Biobank. During a mean follow‐up of 7 years, 14,682 incident cancers were ascertained in 200,289 men and 12,965 cancers in 230,326 women. In men, ABSI was associated positively with cancers of the head and neck (hazard ratio HR = 1.14; 95% confidence interval 1.03–1.26 per one standard deviation increment), esophagus (adenocarcinoma, HR = 1.27; 1.12–1.44), gastric cardia (HR = 1.31; 1.07–1.61), colon (HR = 1.18; 1.10–1.26), rectum (HR = 1.13; 1.04–1.22), lung (adenocarcinoma, HR = 1.16; 1.03–1.30; squamous cell carcinoma [SCC], HR = 1.33; 1.17–1.52), and bladder (HR = 1.15; 1.04–1.27), while HI was associated inversely with cancers of the esophagus (adenocarcinoma, HR = 0.89; 0.79–1.00), gastric cardia (HR = 0.79; 0.65–0.96), colon (HR = 0.92; 0.86–0.98), liver (HR = 0.86; 0.75–0.98), and multiple myeloma (HR = 0.86; 0.75–1.00). In women, ABSI was associated positively with cancers of the head and neck (HR = 1.27; 1.10–1.48), esophagus (SCC, HR = 1.37; 1.07–1.76), colon (HR = 1.08; 1.01–1.16), lung (adenocarcinoma, HR = 1.17; 1.06–1.29; SCC, HR = 1.40; 1.20–1.63; small cell, HR = 1.39; 1.14–1.69), kidney (clear‐cell, HR = 1.25; 1.03–1.50), and post‐menopausal endometrium (HR = 1.11; 1.02–1.20), while HI was associated inversely with skin SCC (HR = 0.91; 0.83–0.99), post‐menopausal kidney cancer (HR = 0.77; 0.67–0.88), and post‐menopausal melanoma (HR = 0.90; 0.83–0.98). Unusually, ABSI was associated inversely with melanoma in men (HR = 0.89; 0.82–0.96) and pre‐menopausal women (HR = 0.77; 0.65–0.91). Waist and hip circumference reflected associations with BMI, when examined individually, and provided biased risk estimates, when combined with BMI. In conclusion, preferential positive associations of ABSI or inverse of HI with several major cancers indicate an important role of factors determining body shape in cancer development.
The predictive value of vessels encapsulating tumor clusters in treatment optimization for recurrent early‐stage hepatocellular carcinoma
Authors: Chen Zhi‐Yuan , Guo Zhi‐Xing , Lu Liang‐He , Mei Jie , Lin Wen‐Ping , Li Shao‐Hua , Wei Wei , Guo Rong‐Ping 
Published: July 2021

AbstractBackgroundThe predictive value of vessels encapsulating tumor clusters (VETC) in recurrent early‐stage hepatocellular carcinoma (HCC) remains unclear. Therefore, the aim of the present study was to investigate the prognostic significance of VETC in patients with recurrent early‐stage HCC after repeat hepatic resection (RHR) or radiofrequency ablation (RFA).MethodsFrom December 2005 to December 2016, 138 patients receiving RHR and 188 patients receiving RFA were recruited. VETC was evaluated by immunohistochemical staining for CD34. The survival outcomes of patients with VETC pattern or not were investigated.ResultsThere was no significant difference between the RHR and RFA groups in disease‐free survival (DFS) or overall survival (OS) as determined by the univariate analysis of the whole cohort. In the subgroup analysis of the VETC‐positive cohort, the patients in the RHR group showed a longer median DFS time in contrast to those in the RFA group (15.0 vs. 5.0 months, p = 0.001). Similarly, the patients in the RHR group showed a longer median OS time in contrast to those in the RFA group (39.5 vs. 19 months, p = 0.001). In the VETC‐negative cohort, no significant differences in DFS and OS rates between the RHR and RFA groups were observed (p > 0.05).ConclusionsThe results of our study suggested that RHR was relatively safe and superior to RFA in improving survival outcomes for recurrent early‐stage HCC after initial hepatectomy. Furthermore, the VETC pattern may represent a reliable marker for selecting HCC patients who may benefit from RHR.
Who is coming through the door? A national survey of self‐reported problems among post‐secondary school students who have attended campus mental health services in Canada
Authors: Ogrodniczuk John S. , Kealy David , Laverdière Olivier 
Published: July 2021

AbstractObjectiveConsiderable evidence has accumulated pointing to a wide array of mental health problems experienced by students attending post‐secondary schools. Yet, much less attention has been focused on understanding who actually accesses mental health services on post‐secondary campuses.MethodsThe current study reports on a national survey of 8,248 students attending 41 post‐secondary campuses across Canada who have accessed their schools' mental health services. The survey solicited self‐reported problems among attendees of campus mental health services. Descriptive statistics (means, frequencies) were utilised to summarise responses to items relating to psychological symptoms, suicidal and self‐injurious behaviours, stress, impediments to academic performance, and future mental health help seeking.ResultsRespondents reported very high levels of stress, with approximately 95% indicating being overwhelmed (n = 7,863) and exhausted (n = 7,803). More than 80% of respondents conveyed feeling very sad (n = 7,200), overwhelming anxiety (n = 6,892) and very lonely (n = 6,670). One quarter (26.1%; n = 2,146) had considered suicide. The most frequently endorsed impediments to academic performance included stress, anxiety, depression and sleep, with nearly three‐quarters (73%; n = 6,018) of respondents indicating that academic work has been traumatic or very difficult to handle.ConclusionThe findings of this survey provide a clearer picture of the types of issues that are brought forth by students who avail themselves of campus mental health services, thus enabling such services to better tailor their offerings to the needs of their clientele.
Interculturality and social skills? Relationships of the stays abroad of students of different faculties with intercultural and social competence
Authors: Genkova Petia , Schreiber Henrik , Gäde Meike 
Published: July 2021

AbstractPossessing skills in social and intercultural interaction is vitally important for employees who work in globalized environments, especially as people's working lives tend to involve an increasingly large amount of service‐related activities. As a consequence, universities offer cultural studies courses and strive to enable their students to study abroad for a period of time. However, there is still no widely shared agreement on how intercultural experiences and cultural preparation courses predict the perception, thinking and acting of individuals. Therefore, the study at hand uses a cross‐sectional design with N = 430 participants in order to investigate whether students of cultural studies gain more intercultural competencies during the time spent studying abroad, compared to studies of other subjects. The results reveal that students of cultural subjects show significantly higher levels of cultural empathy and openness in the post hoc measurement, even though there was no interaction effect with the amount of time spent studying abroad. Length of stay abroad had a significant indirect effect on social competence via all the dimensions of the Multicultural Personality Questionnaire. Moreover, results indicate that flexibility to adapt one's behaviour to cultural norms may predict problems when returning to one's home country.
Cation Ordering and Exsolution in Copper‐Containing Forms of the Flexible Zeolite Rho (Cu,M‐Rho; M=H, Na) and Their Consequences for CO2 Adsorption
Authors: Lozinska Magdalena M. , Jamieson Sophie , Verbraeken Maarten C. , Miller David N. , Bode Bela E. , Murray Claire A. , Brandani Stefano , Wright Paul A. 
Published: July 2021

AbstractThe flexibility of the zeolite Rho framework offers great potential for tunable molecular sieving. The fully copper‐exchanged form of Rho and mixed Cu,H‐ and Cu,Na‐forms have been prepared. EPR spectroscopy reveals that Cu2+ ions are present in the dehydrated forms and Rietveld refinement shows these prefer S6R sites, away from the d8r windows that control diffusion. Fully exchanged Cu‐Rho remains in an open form upon dehydration, the d8r windows remain nearly circular and the occupancy of window sites is low, so that it adsorbs CO2 rapidly at room temperature. Breakthrough tests with 10 % CO2/40 % CH4 mixtures show that Cu4.9‐Rho is able to produce pure methane, albeit with a relatively low capacity at this pCO2 due to the weak interaction of CO2 with Cu cations. This is in strong contrast to Na‐Rho, where cations in narrow elliptical window sites enable CO2 to be adsorbed with high selectivity and uptake but too slowly to enable the production of pure methane in similar breakthrough experiments. A series of Cu,Na‐Rho materials was prepared to improve uptake and selectivity compared to Cu‐Rho, and kinetics compared to Na‐Rho. Remarkably, Cu,Na‐Rho with >2 Cu cations per unit cell exhibited exsolution, due to the preference of Na cations for narrow S8R sites in distorted Rho and of Cu cations for S6R sites in the centric, open form of Rho. The exsolved Cu,Na‐Rho showed improved performance in CO2/CH4 breakthrough tests, producing pure CH4 with improved uptake and CO2/CH4 selectivity compared to that of Cu4.9‐Rho.
Asymmetric Synthesis of Multi‐Substituted Tetrahydrofurans via Palladium/Rhodium Synergistic Catalyzed [3+2] Decarboxylative Cycloaddition of Vinylethylene Carbonates
Authors: Ming Siliang , Qurban Saira , Du Yu , Su Weiping 
Published: July 2021

AbstractUnlike the comprehensive development of tandem multi‐metallic catalysis, bimetallic synergistic catalysis has been challenging to achieve high stereoselectivity with the generation of multi‐stereogenic centers. Herein, an efficient synergistic catalysis for the diastereo‐ and enantioselective synthesis of multi‐substituted tetrahydrofuran derivatives has been developed. Under mild reaction conditions, a series of target molecules with three consecutive stereocenters were synthesized by a palladium(0)/rhodium(III) bimetal‐catalyzed asymmetric decarboxylative [3+2]‐cycloaddition of vinylethylene carbonates with α,β‐unsaturated carbonyl compounds. The corresponding adducts were obtained with moderate to high yields (67 %∼98 %) and excellent stereoselectivities (>20 : 1 d.r., up to 99 % ee).
NHC Effects on Reduction Dynamics in Iron‐Catalyzed Organic Transformations**
Authors: Wolford Nikki J. , Muñoz Salvador B. , Neate Peter G. N. , Brennessel William W. , Neidig Michael L. 
Published: July 2021

AbstractThe high abundance, low toxicity and rich redox chemistry of iron has resulted in a surge of iron‐catalyzed organic transformations over the last two decades. Within this area, N‐heterocyclic carbene (NHC) ligands have been widely utilized to achieve high yields across reactions including cross‐coupling and C−H alkylation, amongst others. Central to the development of iron‐NHC catalytic methods is the understanding of iron speciation and the propensity of these species to undergo reduction events, as low‐valent iron species can be advantageous or undesirable from one system to the next. This study highlights the importance of the identity of the NHC on iron speciation upon reaction with EtMgBr, where reactions with SIMes and IMes NHCs were shown to undergo β‐hydride elimination more readily than those with SIPr and IPr NHCs. This insight is vital to developing new iron‐NHC catalyzed transformations as understanding how to control this reduction by simply changing the NHC is central to improving the reactivity in iron‐NHC catalysis.
Differences in activated clotting time and total unfractionated heparin dose during pulmonary vein isolation in patients on different anticoagulation therapy
Authors: Zeljkovic Ivan , Brusich Sandro , Scherr Daniel , Velagic Vedran , Traykov Vassil , Pernat Andrej , Anic Ante , Szavits Nossan Janko , Jan Matevz , Bakotic Zoran , Pezo Nikolic Borka , Radeljic Vjekoslav , Bojko Ana , Benko Ivica , Manola Sime , Pavlovic Nikola 
Published: July 2021

AbstractBackgroundPeriprocedural pulmonary vein isolation (PVI) anticoagulation requires balancing between bleeding and thromboembolic risk. Intraprocedural anticoagulation is monitored by activated clotting time (ACT) with target value >300 s, and there are no guidelines specifying an initial unfractionated heparin (UFH) dose.MethodsWe aimed to assess differences in ACT values and UFH dosage during PVI in patients on different oral anticoagulants. We conducted an international, multi‐center, registry‐based study. Consecutive patients with atrial fibrillation (AF) undergoing PVI, on uninterrupted anticoagulation therapy, were analyzed. Before transseptal puncture, UFH bolus of 100 IU/kg was administered regardless of the anticoagulation drug.ResultsTotal of 873 patients were included (median age 61 years, IQR 53–66; female 30%). There were 248, 248, 189, 188 patients on warfarin, dabigatran, rivaroxaban, and apixaban, respectively. Mean initial ACT was 257 ± 50 s, mean overall ACT 295 ± 45 s and total UFH dose 158 ± 60 IU/kg. Patients who were receiving warfarin and dabigatran compared to patients receiving rivaroxaban and apixaban had: (i) significantly higher initial ACT values (262 ± 57 and 270 ± 48 vs. 248 ± 42 and 241 ± 44 s, p < .001), (ii) significantly higher ACT throughout PVI (309 ± 46 and 306 ± 44 vs. 282 ± 37 and 272 ± 42 s, p < .001), and (iii) needed lower UFH dose during PVI (140 ± 39 and 157 ± 71 vs. 171 ± 52 and 172 ± 70 IU/kg).ConclusionThere are significant differences in ACT values and UFH dose during PVI in patients receiving different anticoagulants. Patients on warfarin and dabigatran had higher initial and overall ACT values and needed lower UFH dose to achieve adequate anticoagulation during PVI than patients on rivaroxaban and apixaban.
ErbB4 mediates amyloid β‐induced neurotoxicity through JNK/tau pathway activation: Implications for Alzheimer's disease
Authors: Zhang Heng , Zhang Ling , Zhou Dongming , Li Hongfei , Xu Yang 
Published: July 2021

AbstractAccumulation of amyloid β (Aβ) in the brain is a hallmark of Alzheimer's disease (AD). We previously showed that ErbB4 in parvalbumin (PV)‐positive interneurons was associated with Aβ‐induced cognitive deficits; however, the underlying mechanism remains undetermined. Here we found that specific deletion of ErbB4 in PV neurons significantly attenuated oligomeric Aβ‐induced neuronal toxicity and inhibited Aβ‐induced decreases of PSD95 and synaptophysin. Moreover, specific ablation of ErbB4 in PV neurons altered activity‐related protein c‐Fos and decreased hippocampal PV neurons, especially in the dentate gyrus (DG) of hAPP‐J20 mice. Furthermore, c‐Jun N‐terminal kinase (JNK), a protein downstream of ErbB4, was activated by Aβ but not ErbB4's ligand neuregulin 1 (NRG1) β1, suggesting different downstream pathways for Aβ and NRG1β1. JNK phosphorylation was inhibited by the ErbB4 inhibitor AG1478 and by pretreatment with NRG1β1. More importantly, siRNA knockdown of ErbB4 decreased JNK phosphorylation and expression, tau phosphorylation at Ser396 and Thr 205, and Bax expression. Therefore, ErbB4 might mediate Aβ‐induced neuropathology through the JNK/tau pathway and represent a potential therapeutic target in patients with AD.
Emulating Control Arms for Cancer Clinical Trials Using External Cohorts Created From Electronic Health Record‐Derived Real‐World Data
Authors: Tan Katherine , Bryan Jonathan , Segal Brian , Bellomo Lawrence , Nussbaum Nate , Tucker Melisa , Torres Aracelis Z. , Bennette Carrie , Capra William , Curtis Melissa , Miksad Rebecca A. 
Published: July 2021

Electronic health record (EHR)‐derived real‐world data (RWD) can be sourced to create external comparator cohorts to oncology clinical trials. This exploratory study assessed whether EHR‐derived patient cohorts could emulate select clinical trial control arms across multiple tumor types. The impact of analytic decisions on emulation results was also evaluated. By digitizing Kaplan–Meier curves, we reconstructed published control arm results from 15 trials that supported drug approvals from January 1, 2016, to April 30, 2018. RWD cohorts were constructed using a nationwide EHR‐derived de‐identified database by aligning eligibility criteria and weighting to trial baseline characteristics. Trial data and RWD cohorts were compared using Kaplan–Meier and Cox proportional hazards regression models for progression‐free survival (PFS) and overall survival (OS; individual cohorts) and multitumor random effects models of hazard ratios (HRs) for median endpoint correlations (across cohorts). Post hoc, the impact of specific analytic decisions on endpoints was assessed using a case study. Comparing trial data and weighted RWD cohorts, PFS results were more similar (HR range = 0.63–1.18, pooled HR = 0.84, correlation of median = 0.91) compared to OS (HR range = 0.36–1.09, pooled HR = 0.76, correlation of median = 0.85). OS HRs were more variable and trended toward worse for RWD cohorts. The post hoc case study had OS HR ranging from 0.67 (95% confidence interval (CI): 0.56–0.79) to 0.92 (95% CI: 0.78–1.09) depending on specific analytic decisions. EHR‐derived RWD can emulate oncology clinical trial control arm results, although with variability. Visibility into clinical trial cohort characteristics may shape and refine analytic approaches.
Performance analysis of novel fault‐tolerant multilevel inverter with a pristine methodology for fast and exhaustive real‐time failure of switches
Authors: Anand Vishal , Singh Varsha 
Published: July 2021

SummaryMultilevel inverter (MLI) provides a high power density, though the number of devices increases the chances of failures increases, reducing the reliability of power converter. It is essential to detect, isolate, and reconfigure the faults which arises in MLI. The research proposed here is capable of accomplishing the complete fault tolerance against single and multiple devices for both open circuit and short circuit faults. The control algorithm for operation of single‐pole‐double‐throw (SPDT) relays. This methodology is capable of completely preserving the normal operating condition in post‐fault condition also. The output voltage waveform matches by voltage sensors connected across load, and the controllers sense the faults originated from the variation in the look‐up‐table (LUT) and also categorize the nature of the faults. Field‐programmable gate array (FPGA)‐based controller sends a command signal through SPDT to isolate the faulty switches by redundant switches. In this way, the output power across the load is preserved. This research article also covers the comparative study that is made with the existing fault‐tolerant structures. The reliability comparison shows the better performance indices over conventional cascaded H‐bridge (CHB) inverter. The simulation and experimental results validate the effectiveness of control methodology to achieve complete fault tolerance.