bluuebunny/crossref_metadata_2025_split huggingface dataset:
High Wall Shear Stress can Predict Wall Degradation in Ascending Aortic Aneurysms: An Integrated Biomechanics Study
Authors: Salmasi M. Yousuf , Pirola Selene , Sasidharan Sumesh , Fisichella Serena M. , Redaelli Alberto , Jarral Omar A. , O’Regan Declan P. , Oo Aung Ye , Moore James E. , Xu Xiao Yun , Athanasiou Thanos 
Published: October 2021

Background: Blood flow patterns can alter material properties of ascending thoracic aortic aneurysms (ATAA) via vascular wall remodeling. This study examines the relationship between wall shear stress (WSS) obtained from image-based computational modelling with tissue-derived mechanical and microstructural properties of the ATAA wall using segmental analysis.Methods: Ten patients undergoing surgery for ATAA were recruited. Exclusions: bicuspid aortopathy, connective tissue disease. All patients had pre-operative 4-dimensional flow magnetic resonance imaging (4D-MRI), allowing for patient-specific computational fluid dynamics (CFD) analysis and anatomically precise WSS mapping of ATAA regions (6–12 segments per patient). ATAA samples were obtained from surgery and subjected to region-specific tensile and peel testing (matched to WSS segments). Computational pathology was used to characterize elastin/collagen abundance and smooth muscle cell (SMC) count.Results: Elevated values of WSS were predictive of: reduced wall thickness [coef −0.0489, 95% CI (−0.0905, −0.00727), p = 0.022] and dissection energy function (longitudinal) [−15,0, 95% CI (−33.00, −2.98), p = 0.048]. High WSS values also predicted higher ultimate tensile strength [coef 0.136, 95% CI (0 0.001, 0.270), p = 0.048]. Additionally, elevated WSS also predicted a reduction in elastin levels [coef −0.276, 95% (CI −0.531, −0.020), p = 0.035] and lower SMC count ([oef −6.19, 95% CI (−11.41, −0.98), p = 0.021]. WSS was found to have no effect on collagen abundance or circumferential mechanical properties.Conclusions: Our study suggests an association between elevated WSS values and aortic wall degradation in ATAA disease. Further studies might help identify threshold values to predict acute aortic events.
A Novel Brighter Bioluminescent Fusion Protein Based on ZZ Domain and Amydetes vivianii Firefly Luciferase for Immunoassays
Authors: Viviani Vadim R. , Silva Jaqueline Rodrigues , Ho Paulo Lee 
Published: October 2021

Immunoassays are widely used for detection of antibodies against specific antigens in diagnosis, as well as in electrophoretic techniques such as Western Blotting. They usually rely on colorimetric, fluorescent or chemiluminescent methods for detection. Whereas the chemiluminescence methods are more sensitive and widely used, they usually suffer of fast luminescence decay. Here we constructed a novel bioluminescent fusion protein based on the N-terminal ZZ portion of protein A and the brighter green-blue emittingAmydetes vivianiifirefly luciferase. In the presence of D-luciferin/ATP assay solution, the new fusion protein, displays higher bioluminescence activity, is very thermostable and produces a sustained emission (t1/2&gt; 30 min). In dot blots, we could successfully detect rabbit IgG against firefly luciferases, Limpet Haemocyanin, and SARS-CoV-2 Nucleoprotein (1–250 ng), as well as the antigen bound antibodies using either CCD imaging, and even photography using smartphones. Using CCD imaging, we could detect up to 100 pg of SARS-CoV-2 Nucleoprotein. Using this system, we could also successfully detect firefly luciferase and SARS-CoV-2 nucleoprotein in Western Blots (5–250 ng). Comparatively, the new fusion protein displays slightly higher and more sustained luminescent signal when compared to commercial HRP-labeled secondary antibodies, constituting a novel promising alternative for Western Blotting and immunoassays.
Comprehensive Analysis of Regulatory Factors and Immune-Associated Patterns to Decipher Common and BRCA1/2 Mutation-Type-Specific Critical Regulation in Breast Cancer
Authors: Li Yue , Dong Wei , Zhang Pengqian , Zhang Ting , Ma Ling , Qu Meng , Ma Xingcong , Zhou Xiaoyan , He Qian 
Published: October 2021

Background:BRCA1/2 mutations are closely related to high lifetime risk of breast cancer (BC). The objective of this study was to identify the genes, regulators, and immune-associated patterns underlying disease pathology in BC with BRCA1/2 somatic mutations and their associations with clinical traits.Methods: RNA sequencing data and clinical information from The Cancer Genome Atlas (TCGA; N = 36 BRCA1-mutant BC; N = 49 BRCA2-mutant BC; and N = 117 BRCA1/2-wild-type BC samples) were used for discovery, which included consensus network analysis, function enrichment, and analysis of hub genes; other TCGA data (N = 117 triple-negative BC) and two Gene Expression Omnibus database expression profiles were used as validation cohorts.Results: Consensus network analysis helped to identify specific co-expressed modules that showed positive correlations with tumor stage, number of positive lymph nodes, and margin status in BRCA1/2-mutant BC but lacking correlations in BRCA1/2-wild-type BC. Functional enrichment suggested potential mechanisms in BRCA1/2 carriers that could regulate the cell cycle, immune response, cellular metabolic processes, and cell migration, via enriched pathways including p53 and JAK–STAT signaling. Consensus network analysis identified the specific and common carcinogenic mechanisms involving BRCA mutations. Regulators cross-linking these modules include E2F or IRF transcription factor family, associated with cell cycle or immune response regulation module, respectively. Eight hub genes, including ISG15, BUB1, and TTK, were upregulated in several BRCA1/2-mutant BC datasets and showed prognostic value in BC. Furthermore, their genetic expression was related to higher levels of immune infiltration in BRCA1/2-mutant BC, which manifested as recruitment of T helper cells (Th1 cells), follicular helper T cells, and regulatory T cells, and T cell exhaustion. Moreover, important indicators for evaluation of BC immunotherapy, tumor mutational burden and neoantigen load also positively correlated with expression of some hub genes.Conclusion: We constructed a BRCA1/2 mutation-type-specific co-expressed gene network with related transcription factors and immune-associated patterns that could regulate and influence tumor metastasis and immune microenvironment, providing novel insights into the pathological process of this disease and the corresponding BRCA mutations.
Crosstalk Between MicroRNAs and Circular RNAs in Human Diseases: A Bibliographic Study
Authors: Chen Yu-Meng , Zheng Yi-Li , Su Xuan , Wang Xue-Qiang 
Published: October 2021

Background: Crosstalk of circular RNAs (circRNAs) and microRNAs (miRNAs) refers to the communication and co-regulation between them. circRNAs can act as miRNAs sponges, and miRNAs can mediate circRNAs. They interact to regulate gene expression and participate in the occurrence and development of various human diseases.Methods: Publications on the crosstalk between miRNAs and circRNAs in human diseases were collected from Web of Science. The collected material was limited to English articles and reviews. CiteSpace and Microsoft Excel were used for bibliographic analysis.Results: A total of 1,013 papers satisfied the inclusion criteria. The publication outputs and types of researched diseases were analyzed, and bibliographic analysis was used to characterize the most active journals, countries, institutions, keywords, and references. The annual number of publications remarkably increased from 2011 to 2020. Neoplasm was the main research hotspot (n = 750 publications), and Biochemical and Biophysical Research Communications published the largest number of papers (n = 64) on this topic. Nanjing Medical University ranked first among institutions actively engaged in this field by publishing 72 papers, and China contributed 96.84% of the 1,013 papers (n = 981 publications) analyzed. Burst keywords in recent years included glioblastoma, miR-7, skeletal muscle, and non-coding RNA.Conclusion: Crosstalk between miRNAs and circRNAs in human diseases is a popular research topic. This study provides important clues on research trends and frontiers.
Mechanical Stability Is Key for Large-Scale Implementation of Photocatalytic Surface-Attached Film Technologies in Water Treatment
Authors: Ramos D.R. , Iazykov M. , Fernandez M.I. , Santaballa J.A. , Canle M. 
Published: October 2021

Replacement of classical tertiary water treatment by chemical-free sunlight-driven photocatalytic units has been often proposed. Photocatalysts are required to be cost-effective, inert, chemically stable, reusable, and easy to separate and also that they are mechanically stable. The effect of mechanical stress on a photoactive TiO2 layer, and on its effectivity for degradation of phenol as a model pollutant, has been studied during photocatalytic water treatment using NUV–vis light. Sol–gel (SG) and liquid phase deposition (LPD) methods have been used to coat spherical glass beads with the photocatalyst (TiO2). Physicochemical characterization of coated glass beads has been performed by N2 adsorption–desorption isotherms, SEM, EDXS, and AFM. Phenol photocatalyzed degradation was carried out both in stirred batch and flow reactors irradiated with a medium-pressure Hg-vapor lamp (λ &gt; 350 nm). Phenol concentration was determined by HPLC, and its photoproducts were identified using HPLC/MS. In the stirred batch reactor, all LPD-coated glass beads displayed higher catalytic activity than SG-coated ones, which increased with calcination temperature, 700°C being the most efficient temperature. Preliminary etching of the glass beads surface yielded dissimilar results; whereas, phenol photodegradation with SG-coated etched glass beads is twice faster than with unetched SG ones, the rate reduces to one-third using LPD etched instead of unetched LPD glass beads. Phenol photodegradation using LPD is similar both in stirred batch and flow reactors, despite the latter uses a lower catalyst load. LPD-etched catalyst was recovered and reused in the stirred batch reactor; its activity reduced sharply after the first use, and it also lost activity in successive runs, ca. 10% of activity after each “use and recover” cycle. In the flow reactor, activity loss after the first experiment and recycling (ca. 30%) was much larger than in the following runs, where the activity remained rather constant through several cycles. LPD is more adequate than SG for TiO2 immobilization onto glass beads, and their calcination at 700°C leads to relatively strong and reactive photocatalytic films. Still, TiO2-coated glass beads exhibited very low photoactivity compared to TiO2-P25 nanoparticles, though their separation is much easier and almost costless. The durability of the catalytic layer increases when using a flow reactor, with the pollutant solution flowing in a laminar regime through the photocatalyst bed. In this way, the abrasion of the photocatalytic surface is largely reduced and its photoactivity is better maintained.
MiR-320d Inhibits Progression of EGFR-Positive Colorectal Cancer by Targeting TUSC3
Authors: Yufeng Zhu , Ming Qi , Dandan Wu 
Published: October 2021

Background: The mechanism of miR-320d in EGFR-positive colorectal cancer (CRC) has not been fully elucidated. The aim of the present study was to explore the molecular mechanism of miR-320d in CRC.Methods: The miRNA microarray analysis was conducted to identify differential expressed miRNAs. The expression of miR-320d was validated using quantitative real-time PCR. EGFR-positive CRC cells were transfected with miR-320d mimic and inhibitor, after which cell proliferation, migration, and invasion were assayed. The relationship between miR-320d and TUSC3 was confirmed using bioinformatics and dual-luciferase reporter gene assays. Proteins involved in signaling pathways and the epithelial–mesenchymal transition were detected with Western blot.Results: We found that the miR-320d expression is associated with tumor size and distant metastasis in colorectal cancer. Overexpression of miR-320d in EGFR-positive HCT-116 and SW480 cells decreased not only the proliferation ability but also the invasion and migration ability. In addition, miR-320d had the ability to inhibit epithelial-to-mesenchymal transition. Luciferase assays revealed that miR-320d directly targets the 3′-UTR of TUSC3. TUSC3 was downregulated by miR-320d at both the protein and mRNA levels in EGFR-positive CRC cell lines.Conclusion: Generally, our results demonstrated that miR-320d could inhibit the malignant phenotype of EGFR-positive CRC through targeting TUSC3. The miR-320d might be a potential therapeutic target for EGFR-positive CRC.
Long-Term Retinal Neurovascular and Choroidal Changes After Panretinal Photocoagulation in Diabetic Retinopathy
Authors: Huang Tian , Li Xiaoli , Xie Jie , Zhang Liang , Zhang Guanrong , Zhang Aiping , Chen Xiangting , Cui Ying , Meng Qianli 
Published: October 2021

Purpose: To evaluate the long-term retinal microvascular, neural, and choroidal changes in the patients with severe nonproliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) following panretinal photocoagulation (PRP).Methods: Forty-five eyes of 28 patients with treatment-naive severe NPDR and PDR were included and followed for 12 months after PRP. Microvascular and neural changes in the macular and peripapillary areas were assessed by using optical coherence tomography angiography. Subfoveal choroidal thickness (SFCT) was measured by using optical coherence tomography. A Linear mixed-effects model was used to highlight the differences for the variables after adjusting for sex, age, and axial length.Results: Compared to baseline, there were no statistical differences in the best corrected visual acuity (BCVA), macular and peripapillary vessel density (VD), and SFCT following PRP. Macular thickness significantly increased at 1 and 3–6 months after PRP (p &lt; 0.05), while the peripapillary retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thickness significantly increased at 1 month postoperatively (p &lt; 0.01). Global loss volume and focal loss volume significantly decreased at the same time point (p &lt; 0.05).Conclusion: The unchanged BCVA, VD, the thickness of RNFL and GCC, and SFCT during the 12-month follow-up period suggest that PRP may prevent the retinal neurovascular and choroidal damage.
ARV-825 Demonstrates Antitumor Activity in Gastric Cancer via MYC-Targets and G2M-Checkpoint Signaling Pathways
Authors: Liao Xinmei , Qian Xiaoqing , Zhang Zimu , Tao Yanfang , Li Zhiheng , Zhang Qian , Liang Hui , Li Xiaolu , Xie Yi , Zhuo Ran , Chen Yanling , Jiang You , Cao Haibo , Niu Jiaqi , Xue Cuili , Ni Jian , Pan Jian , Cui Daxiang 
Published: October 2021

ObjectiveSuppression of bromodomain and extra terminal (BET) proteins has a bright prospect to treat MYC-driven tumors. Bromodomain containing 4 (BRD4) is one of the BET proteins. ARV-825, consisting of a BRD4 inhibitor conjugated with a cereblon ligand using proteolysis-targeting chimera (PROTAC) technology, was proven to decrease the tumor growth effectively and continuously. Nevertheless, the efficacy and mechanisms of ARV-825 in gastric cancer are still poorly understood.MethodsCell counting kit 8 assay, lentivirus infection, Western blotting analysis, Annexin V/propidium iodide (PI) staining, RNA sequencing, a xenograft model, and immunohistochemistry were used to assess the efficacy of ARV-825 in cell level and animal model.ResultsThe messenger RNA (mRNA) expression of BRD4 in gastric cancer raised significantly than those in normal tissues, which suggested poor outcome of patients with gastric cancer. ARV-825 displayed higher anticancer efficiency in gastric cancer cells than OTX015 and JQ1. ARV-825 could inhibit cell growth, inducing cell cycle block and apoptosis in vitro. ARV-825 induced degradation of BRD4, BRD2, BRD3, c-MYC, and polo-like kinase 1 (PLK1) proteins in four gastric cancer cell lines. In addition, cleavage of caspase 3 and poly-ADP-ribose polymerase (PARP) was elevated. Knockdown or overexpression CRBN could increase or decrease, respectively, the ARV-825 IC50 of gastric cancer cells. ARV-825 reduced MYC and PLK1 expression in gastric cancer cells. ARV-825 treatment significantly reduced tumor growth without toxic side effects and downregulated the expression of BRD4 in vivo.ConclusionsHigh mRNA expression of BRD4 in gastric cancer indicated poor prognosis. ARV-825, a BRD4 inhibitor, could effectively suppress the growth and elevate the apoptosis of gastric cancer cells via transcription downregulation of c-MYC and PLK1. These results implied that ARV-825 could be a good therapeutic strategy to treat gastric cancer.
Initial Incomplete Thermal Ablation Is Associated With a High Risk of Tumor Progression in Patients With Hepatocellular Carcinoma
Authors: Tan Jie , Tang Tian , Zhao Wei , Zhang Zi-Shu , Xiao Yu-Dong 
Published: October 2021

PurposeTo investigate whether incomplete thermal ablation is associated with a high risk of tumor progression in patients with hepatocellular carcinoma (HCC), and to compare the efficacy of repeated thermal ablation and transarterial chemoembolization (TACE) for residual tumor after incomplete ablation.MethodsThis retrospective study included 284 patients with unresectable HCC who underwent thermal ablation from June 2014 to September 2020. The response of the initially attempted ablation was classified into complete (n=236) and incomplete (n=48). The progression-free survival (PFS) and overall survival (OS) were compared between patients with complete and incomplete responses, before and after a one-to-one propensity score-matching (PSM), and between patients in whom repeated ablation or TACE was performed after a first attempt incomplete ablation.ResultsAfter PSM of the 284 patients, 46 pairs of patients were matched. The PFS was significantly higher in the complete response group than in the incomplete response group (P&lt;0.001). No difference in OS was noted between two groups (P=0.181). After a first attempt incomplete ablation, 29 and 19 patients underwent repeated ablation and TACE, respectively. There were no significant differences in PFS (P=0.424) and OS (P=0.178) between patients who underwent repeated ablation and TACE. In multivariate Cox regression analysis, incomplete response (P&lt;0.001) and Child-Pugh class B (P=0.017) were independent risk factors for tumor progression, while higher AFP level (P=0.011) and Child-Pugh class B (P=0.026) were independent risk factors for poor OS.ConclusionAlthough patients with incomplete ablation are associated with tumor progression compared with those with complete ablation, their OS is not affected by incomplete ablation. When patients present with residual tumors, TACE may be an alternative if repeated ablation is infeasible.
BuqiTongluo Granule for Ischemic Stroke, Stable Angina Pectoris, Diabetic Peripheral Neuropathy with Qi Deficiency and Blood Stasis Syndrome: Rationale and Novel Basket Design
Authors: Liu Weidi , Zhou Li , Feng Luda , Zhang Dandan , Zhang Chi , Gao Ying ,   behalf of the BOSS Group
Published: October 2021

Background: BuqiTongluo (BQTL) granules are herbal phenotypic drugs for Qi deficiency and blood stasis (QDBS) syndrome. Its discovery relied primarily on knowledge of observable phenotypic changes associated with diseases. Although BQTL granules have been widely advocated by Chinese Medicine (CM) practitioners, its use lacks empirical support.Aim of the study: In this basket trial, the efficacy of BQTL granules in multiple diseases that have the QDBS syndrome in common will be compared with placebo.Materials and Methods: The BuqiTongluo granule for Qi deficiency and blood stasis syndrome (BOSS) study is a basket herbal trial (ClinicalTrials.gov, NCT04408261). It will be a double-blinded, randomized, placebo-controlled, parallel, multicenter, clinical trial. In total, 432 patients (1:1:1 ischemic stroke, stable angina pectoris, and diabetic peripheral neuropathy), who meet the operationalized diagnostic criteria for QDBS syndrome, have been recruited and randomized in a ratio of 1:1 to receive 6 weeks’ treatment with BQTL granules or placebo. The primary outcome is the change in the QDBS syndrome score at week 6 from baseline. Secondary outcomes include objective outcome measures for the three diseases and adverse events. Omics will help to understand these responses by molecular events.Conclusion: QDBS syndrome is a common phenotypic marker that was hypothesized to predict whether patients with multiple diseases would respond to this targeted therapy. No previous basket trial has assessed the potential efficacy of an herbal intervention for multiple diseases. The unique promise of the trial is its ability to exploit a disease phenotype to discover novel treatments for three diseases for which the root cause is unknown, complex, or multifactorial, and for which scientific understanding is insufficient to provide valid molecular targets.
Psychiatric Comorbidity and Economic Hardship as Risk Factors for Intentional Self-Harm in Gambling Disorder—A Nationwide Register Study
Authors: Karlsson Anna , Hedén Olivia , Hansson Helena , Sandgren Jenny , Håkansson Anders 
Published: October 2021

Background: There is an increased risk of suicidality in gambling disorder (GD) and economic hardship is common in the population. Economic hardship itself is a risk factor for suicidality. This study aims to explore the risk of intentional self-harm in GD utilizing social welfare payment (SWP) as a proxy for economic hardship and exploring how economic hardship, gender, criminality, socioeconomic-, and psychiatric risk factors might contribute to intentional self-harm in GD.Methods: This is a nationwide register-based study of 848 individuals diagnosed with GD in the Swedish healthcare system during the years of 2011–2014 with an average follow up of 4.9 years. Pearson's Chi-square analyses were carried out for comparisons regarding psychiatric comorbidity and intentional self-harm with regards to gender and SWPs. Univariable and multivariable Cox regression were utilized to analyse risk factors for intentional self-harm.Results: A large part of the study population received SWPs (45.5% with an insignificant overrepresentation of women) and psychiatric disorders were more common in these individuals (p &lt; 0.001). Conviction for crime in general (p &lt; 0.001) as well as intentional self-harm (p = 0.025) were also more common amongst recipients of SWPs. Criminal conviction in general was abundant (26.5%). In the stepwise multivariable regression, substance-related diagnoses as well as anxiety, depressive, and personality disorders remained risk factors for intentional self-harm and no significant results were found with regards to gender, criminal history, or SWPs.Conclusions: Social welfare payment was common among GD patients and intentional self-harm was more common amongst recipients than GD patients as a whole. Social welfare payments were however not a significant risk factor for intentional self-harm. However, attention to suicidality and self-injurious behavior should be paid from social services controlling SWPs due to the large prevalence of intentional self-harm in this group. In accordance with previous studies, comorbid psychiatric disorders such as anxiety, depression, substance use, and personality disorders increased the risk of intentional self-harm.