bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnetic Resonance Imaging-Guided Adaptive Radiotherapy for Colorectal Liver Metastases
Authors: Romesser Paul B. , Tyagi Neelam , Crane Christopher H.
Published: April 2021

Technological advances have enabled well tolerated and effective radiation treatment for small liver metastases. Stereotactic ablative radiation therapy (SABR) refers to ablative dose delivery (>100 Gy BED) in five fractions or fewer. For larger tumors, the safe delivery of SABR can be challenging due to a more limited volume of healthy normal liver parenchyma and the proximity of the tumor to radiosensitive organs such as the stomach, duodenum, and large intestine. In addition to stereotactic treatment delivery, controlling respiratory motion, the use of image guidance, adaptive planning and increasing the number of radiation fractions are sometimes necessary for the safe delivery of SABR in these situations. Magnetic Resonance (MR) image-guided adaptive radiation therapy (MRgART) is a new and rapidly evolving treatment paradigm. MR imaging before, during and after treatment delivery facilitates direct visualization of both the tumor target and the adjacent normal healthy organs as well as potential intrafraction motion. Real time MR imaging facilitates non-invasive tumor tracking and treatment gating. While daily adaptive re-planning permits treatment plans to be adjusted based on the anatomy of the day. MRgART therapy is a promising radiation technology advance that can overcome many of the challenges of liver SABR and may facilitate the safe tumor dose escalation of colorectal liver metastases.
DPP9: Comprehensive In Silico Analyses of Loss of Function Gene Variants and Associated Gene Expression Signatures in Human Hepatocellular Carcinoma
Authors: Huang Jiali Carrie , Emran Abdullah Al , Endaya Justine Moreno , McCaughan Geoffrey W. , Gorrell Mark D. , Zhang Hui Emma
Published: April 2021

Dipeptidyl peptidase (DPP) 9, DPP8, DPP4 and fibroblast activation protein (FAP) are the four enzymatically active members of the S9b protease family. Associations of DPP9 with human liver cancer, exonic single nucleotide polymorphisms (SNPs) in DPP9 and loss of function (LoF) variants have not been explored. Human genomic databases, including The Cancer Genome Atlas (TCGA), were interrogated to identify DPP9 LoF variants and associated cancers. Survival and gene signature analyses were performed on hepatocellular carcinoma (HCC) data. We found that DPP9 and DPP8 are intolerant to LoF variants. DPP9 exonic LoF variants were most often associated with uterine carcinoma and lung carcinoma. All four DPP4-like genes were overexpressed in liver tumors and their joint high expression was associated with poor survival in HCC. Increased DPP9 expression was associated with obesity in HCC patients. High expression of genes that positively correlated with overexpression of DPP4, DPP8, and DPP9 were associated with very poor survival in HCC. Enriched pathways analysis of these positively correlated genes featured Toll-like receptor and SUMOylation pathways. This comprehensive data mining suggests that DPP9 is important for survival and that the DPP4 protease family, particularly DPP9, is important in the pathogenesis of human HCC.
Systematic Assessment of Transcriptomic Biomarkers for Immune Checkpoint Blockade Response in Cancer Immunotherapy
Authors: Sun Shangqin , Xu Liwen , Zhang Xinxin , Pang Lin , Long Zhilin , Deng Chunyu , Zhu Jiali , Zhou Shuting , Wan Linyun , Pang Bo , Xiao Yun
Published: April 2021

Background: Immune checkpoint blockade (ICB) therapy has yielded successful clinical responses in treatment of a minority of patients in certain cancer types. Substantial efforts were made to establish biomarkers for predicting responsiveness to ICB. However, the systematic assessment of these ICB response biomarkers remains insufficient. Methods: We collected 22 transcriptome-based biomarkers for ICB response and constructed multiple benchmark datasets to evaluate the associations with clinical response, predictive performance, and clinical efficacy of them in pre-treatment patients with distinct ICB agents in diverse cancers. Results: Overall, “Immune-checkpoint molecule” biomarkers PD-L1, PD-L2, CTLA-4 and IMPRES and the “Effector molecule” biomarker CYT showed significant associations with ICB response and clinical outcomes. These immune-checkpoint biomarkers and another immune effector IFN-gamma presented predictive ability in melanoma, urothelial cancer (UC) and clear cell renal-cell cancer (ccRCC). In non-small cell lung cancer (NSCLC), only PD-L2 and CTLA-4 showed preferable correlation with clinical response. Under different ICB therapies, the top-performing biomarkers were usually mutually exclusive in patients with anti-PD-1 and anti-CTLA-4 therapy, and most of biomarkers presented outstanding predictive power in patients with combined anti-PD-1 and anti-CTLA-4 therapy. Conclusions: Our results show these biomarkers had different performance in predicting ICB response across distinct ICB agents in diverse cancers.
Urine HPV in the Context of Genital and Cervical Cancer Screening—An Update of Current Literature
Authors: Daponte Alexandros , Michail George , Daponte Athina-Ioanna , Daponte Nikoletta , Valasoulis George
Published: April 2021

Within the previous decades, following the widespread implementation of HPV-related biomarkers and computerization in liquid-based cytology, screening for lower genital tract malignancies has been optimized in several parts of the world. Many organized anogenital cancer prevention systems have reached a point at which efficacy is more a matter of population coverage and less of available infrastructures. Meanwhile, self-sampling modalities in which biologic material (vaginal secretions, urine, etc.) is obtained by the individual and not the clinician and subsequently undergoes examination for HPV biomarkers enjoy appreciating acceptance. Bygone the initial skepticism that vaginal or urine HPV represents “passenger” transient infections, extensive scientific work has been conducted to optimize high-risk HPV (hrHPV) detection from this “novel” biologic material. Nowadays, several state-of-the-art meta-analyses have illustrated that self-sampling techniques involving urine self-sampling represent a feasible alternative strategy with potentially enhanced population coverage possessing excellent performance and sensitivity. Recently published scientific work focusing on urine HPV was reviewed, and after a critical appraisal, the following points should be considered in the clinical application of hrHPV urine measurements; (i) use of first-void urine (FVU) and purpose-designed collection devices; (ii) using a preservation medium to avoid human/HPV DNA degradation during extraction and storage; (iii) using polymerase chain reaction (PCR) based assays, ideally with genotyping capabilities; (iv) processing of a sufficient volume of whole urine; and (v) the use of an analytically sensitive HPV test/recovery of cell-free HPV DNA in addition to cell-associated DNA.
Meta-Analysis of Gastrointestinal Adverse Events from Tyrosine Kinase Inhibitors for Chronic Myeloid Leukemia
Authors: Mohanavelu Prahathishree , Mutnick Mira , Mehra Nidhi , White Brandon , Kudrimoti Sparsh , Hernandez Kluesner Kaci , Chen Xinyu , Nguyen Tim , Horlander Elaina , Thenot Helena , Kota Vamsi , Mitchell Cassie S.
Published: April 2021

Tyrosine kinase inhibitors (TKIs) are the frontline therapy for BCR-ABL (Ph+) chronic myeloid leukemia (CML). A systematic meta-analysis of 43 peer-reviewed studies with 10,769 CML patients compared the incidence of gastrointestinal adverse events (GI AEs) in a large heterogeneous CML population as a function of TKI type. Incidence and severity of nausea, vomiting, and diarrhea were assessed for imatinib, dasatinib, bosutinib, and nilotinib. Examination of combined TKI average GI AE incidence found diarrhea most prevalent (22.5%), followed by nausea (20.6%), and vomiting (12.9%). Other TKI GI AEs included constipation (9.2%), abdominal pain (7.6%), gastrointestinal hemorrhage (3.5%), and pancreatitis (2.2%). Mean GI AE incidence was significantly different between TKIs (p < 0.001): bosutinib (52.9%), imatinib (24.2%), dasatinib (20.4%), and nilotinib (9.1%). Diarrhea was the most prevalent GI AE with bosutinib (79.2%) and dasatinib (28.1%), whereas nausea was most prevalent with imatinib (33.0%) and nilotinib (13.2%). Incidence of grade 3 or 4 severe GI AEs was ≤3% except severe diarrhea with bosutinib (9.5%). Unsupervised clustering revealed treatment efficacy measured by the complete cytogenetic response, major molecular response, and overall survival is driven most by disease severity, not TKI type. For patients with chronic phase CML without resistance, optimal TKI selection should consider TKI AE profile, comorbidities, and lifestyle.
HDAC6 Signaling at Primary Cilia Promotes Proliferation and Restricts Differentiation of Glioma Cells
Authors: Shi Ping , Hoang-Minh Lan B. , Tian Jia , Cheng Alice , Basrai Reemsha , Kalaria Neil , Lebowitz Joseph J. , Khoshbouei Habibeh , Deleyrolle Loic P. , Sarkisian Matthew R.
Published: April 2021

Histone deacetylase 6 (HDAC6) is an emerging therapeutic target that is overexpressed in glioblastoma when compared to other HDACs. HDAC6 catalyzes the deacetylation of alpha-tubulin and mediates the disassembly of primary cilia, a process required for cell cycle progression. HDAC6 inhibition disrupts glioma proliferation, but whether this effect is dependent on tumor cell primary cilia is unknown. We found that HDAC6 inhibitors ACY-1215 (1215) and ACY-738 (738) inhibited the proliferation of multiple patient-derived and mouse glioma cells. While both inhibitors triggered rapid increases in acetylated alpha-tubulin (aaTub) in the cytosol and led to increased frequencies of primary cilia, they unexpectedly reduced the levels of aaTub in the cilia. To test whether the antiproliferative effects of HDAC6 inhibitors are dependent on tumor cell cilia, we generated patient-derived glioma lines devoid of cilia through depletion of ciliogenesis genes ARL13B or KIF3A. At low concentrations, 1215 or 738 did not decrease the proliferation of cilia-depleted cells. Moreover, the differentiation of glioma cells that was induced by HDAC6 inhibition did not occur after the inhibition of cilia formation. These data suggest HDAC6 signaling at primary cilia promotes the proliferation of glioma cells by restricting their ability to differentiate. Surprisingly, overexpressing HDAC6 did not reduce cilia length or the frequency of ciliated glioma cells, suggesting other factors are required to control HDAC6-mediated cilia disassembly in glioma cells. Collectively, our findings suggest that HDAC6 promotes the proliferation of glioma cells through primary cilia.
Expression of SEC62 Oncogene in Benign, Malignant and Borderline Melanocytic Tumors—Unmasking the Wolf in Sheep’s Clothing?
Authors: Müller Cornelia S. L. , Pföhler Claudia , Wahl Maria , Bochen Florian , Körner Sandrina , Kühn Jan Philipp , Bozzato Alessandro , Schick Bernhard , Linxweiler Maximilian
Published: April 2021

SEC62 oncogene located at chromosomal region 3q26 encodes for a transmembrane protein of the endoplasmic reticulum (ER) and is expressed at high levels in numerous human malignancies. SEC62 overexpression has been associated with worse prognosis and high risk for lymphatic and distant metastases in head and neck cancer, cervical cancer, hepatocellular cancer, and lung cancer. However, its role in the development and tumor biology of melanocytic lesions has not been investigated so far. An immunohistochemical study including 209 patients with melanocytic lesions (malignant melanoma (MM), n = 93; melanoma metastases (MET), n = 28; Spitz nevi (SN), n = 29; blue nevi (BN), n = 21; congenital nevi (CN), n = 38) was conducted and SEC62 expression was correlated with clinical data including patient survival and histopathological characteristics. SN showed the highest SEC62 expression levels followed by MET, MM, CN, and BN. High SEC62 expression correlated with a shorter overall and progression-free survival in MM patients. Additionally, high Sec62 levels correlated significantly with higher tumor size (T stage), the presence of tumor ulceration, and the presence of lymph node as well as distant metastases. Strikingly, SEC62 expression showed a strong correlation with Clark level. Taken together, these data demonstrate that SEC62 is a promising prognostic marker in MM and has the potential to predict biological behavior and clinical aggressiveness of melanocytic lesions.
Death Receptor 5 (TNFRSF10B) Is Upregulated and TRAIL Resistance Is Reversed in Hypoxia and Normoxia in Colorectal Cancer Cell Lines after Treatment with Skyrin, the Active Metabolite of Hypericum spp.
Authors: Babinčák Marián , Jendželovský Rastislav , Košuth Ján , Majerník Martin , Vargová Jana , Mikulášek Kamil , Zdráhal Zbyněk , Fedoročko Peter
Published: April 2021

Skyrin (SKR) is a plant bisanthraquinone secondary metabolite from the Hypericum genus with potential use in anticancer therapy. However, its effect and mechanism of action are still unknown. The negative effect of SKR on HCT 116 and HT-29 cancer cell lines in hypoxic and normoxic conditions was observed. HCT 116 cells were more responsive to SKR treatment as demonstrated by decreased metabolic activity, cellularity and accumulation of cells in the G1 phase. Moreover, an increasing number of apoptotic cells was observed after treatment with SKR. Based on the LC-MS comparative proteomic data from hypoxia and normoxia (data are available via ProteomeXchange with the identifier PXD019995), SKR significantly upregulated Death receptor 5 (DR5), which was confirmed by real-time qualitative PCR (RT-qPCR). Furthermore, multiple changes in the Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-activated cascade were observed. Moreover, the reversion of TRAIL resistance was observed in HCT 116, HT-29 and SW620 cell lines, even in hypoxia, which was linked to the upregulation of DR5. In conclusion, our results propose the use of SKR as a prospective anticancer drug, particularly as an adjuvant to TRAIL-targeting treatment to reverse TRAIL resistance in hypoxia.
Prognostic Significance of Glucocorticoid Receptor Expression in Cancer: A Systematic Review and Meta-Analysis
Authors: Bakour Noor , Moriarty Frank , Moore Gillian , Robson Tracy , Annett Stephanie L.
Published: April 2021

In solid malignancies, the glucocorticoid receptor (GR) signalling axis is associated with tumour progression and GR antagonists are in clinical development. Therefore, GR expression may be a useful potential prognostic or predictive biomarker for GR antagonist therapy in cancer. The aim of this review is to investigate if GR expression in tumours is predictive of overall survival or progression free survival. Twenty-five studies were identified through systematic searches of three databases and a meta-analysis conducted using a random effects model, quantifying statistical heterogeneity. Subgroup analysis was conducted for cancer types and publication bias was assessed via funnel plots. There was high heterogeneity in meta-analysis of the studies in all cancer types, which found no association between high GR expression with overall survival (pooled unadjusted HR 1.16, 95% CI (0.89–1.50), n = 2814; pooled adjusted HR 1.02, 95% CI (0.77–1.37), n = 2355) or progression-free survival (pooled unadjusted HR 1.12, 95% CI (0.88–1.42), n = 3365; pooled adjusted HR 1.04, 95% CI (0.6–1.81), n = 582) across all cancer types. However, subgroup meta-analyses showed that high GR expression in gynaecological cancers (endometrial and ovarian) (unadjusted HR 1.83, 95% CI (1.31–2.56), n = 664) and early stage, untreated triple negative breast cancers (TNBCs) (unadjusted HR 1.73, 95% CI (1.35–2.23), n = 687) is associated with disease progression. GR expression in late stage, chemotherapy treated TNBC was not prognostic (unadjusted HR 0.76, 95% CI (0.44, 1.32), n = 287). In conclusion, high GR expression is associated with an increased risk of disease progression in gynaecological and early stage, untreated TNBC. Additional studies are required to elucidate the tumour specific function of the GR receptor in order to ensure GR antagonists target the correct patient groups.
Novel HER2-Directed Treatments in Advanced Gastric Carcinoma: AnotHER Paradigm Shift?
Authors: Ricci Angela Dalia , Rizzo Alessandro , Rojas Llimpe Fabiola Lorena , Di Fabio Francesca , De Biase Dario , Rihawi Karim
Published: April 2021

Human epidermal growth factor receptor 2 (HER2) is overexpressed and/or amplified in approximately 15–20% of gastric adenocarcinoma (GC) patients. In 2010, the landmark ToGA trial established the combination of trastuzumab plus chemotherapy as the first-line standard of care for HER2-positive GC patients with advanced disease. However, subsequent studies on HER2 targeted therapies in this setting failed to meet their primary endpoints, and not all HER2-positive GC patients benefit from targeted approaches. More recently, novel HER2-directed treatments have been investigated, including trastuzumab deruxtecan (T-Dxd); following the results of the DESTINY-Gastric01 study, T-Dxd received its first U.S. Food and Drug Administration (FDA) approval on 15 January 2021 for the treatment of adults with unresectable, locally advanced, or metastatic GC who have received a prior trastuzumab-based regimen. In this review, we discuss the current HER2-targeted treatments for GC in the advanced disease setting, mainly focusing on emerging new treatments and future research directions.
Chromatin Regulator SPEN/SHARP in X Inactivation and Disease
Authors: Giaimo Benedetto , Robert-Finestra Teresa , Oswald Franz , Gribnau Joost , Borggrefe Tilman
Published: April 2021

Enzymes, such as histone methyltransferases and demethylases, histone acetyltransferases and deacetylases, and DNA methyltransferases are known as epigenetic modifiers that are often implicated in tumorigenesis and disease. One of the best-studied chromatin-based mechanism is X chromosome inactivation (XCI), a process that establishes facultative heterochromatin on only one X chromosome in females and establishes the right dosage of gene expression. The specificity factor for this process is the long non-coding RNA Xinactivespecifictranscript (Xist), which is upregulated from one X chromosome in female cells. Subsequently, Xist is bound by the corepressor SHARP/SPEN, recruiting and/or activating histone deacetylases (HDACs), leading to the loss of active chromatin marks such as H3K27ac. In addition, polycomb complexes PRC1 and PRC2 establish wide-spread accumulation of H3K27me3 and H2AK119ub1 chromatin marks. The lack of active marks and establishment of repressive marks set the stage for DNA methyltransferases (DNMTs) to stably silence the X chromosome. Here, we will review the recent advances in understanding the molecular mechanisms of how heterochromatin formation is established and put this into the context of carcinogenesis and disease.
Density Functional Theory (DFT) Calculations and Catalysis
Authors: Lee Yong-Kul
Published: April 2021

Catalysis plays a fundamental role in the establishment of sustainable chemical technologies that are efficient in terms of energy and atoms [...]
Regulatory and Effector Cell Disequilibrium in Patients with Acute Cellular Rejection and Chronic Lung Allograft Dysfunction after Lung Transplantation: Comparison of Peripheral and Alveolar Distribution
Authors: Bergantini Laura , d’Alessandro Miriana , De Vita Elda , Perillo Felice , Fossi Antonella , Luzzi Luca , Paladini Piero , Perrone Anna , Rottoli Paola , Sestini Piersante , Bargagli Elena , Bennett David
Published: April 2021

Background: The immune mechanisms occurring during acute rejection (AR) and chronic lung allograft dysfunction are a challenge for research and the balance between effector and regulatory cells has not been defined completely. In this study, we aimed to elucidate the interaction of effector cells, mainly Th17, Th1 and Th2, and regulatory cells including (CD4+CD25+CD127low/−) T reg cells and phenotypes of B regs, CD19+CD24hiCD38hi, CD19+CD24hiCD27hi and CD19+CD5+CD1d+. Methods: Bronchoalveolar lavage cells (BAL) and peripheral blood mononuclear cells (PBMCs) from stable lung transplanted (LTx )subjects (n = 4), AR patients (n = 6) and bronchiolitis obliterans syndrome (BOS) (n = 6) were collected at the same time. Cellular subsets were detected through flow cytometry. Results: A predominance of Th17 cells subtypes in the PBMCs and BAL and a depletion of Tregs, that resulted in decrease Treg/Th17 ratio, was observed in the AR group. CD19+CD24hiCD38hi Bregs resulted increased in BAL of AR patients. Th1 cells predominance and a reduction of Tregs cells was observed in BAL from AR patients. Moreover, multivariate analysis showed interdependences within studied variables revealing that effector cells and regulatory cells can effectively discriminate patients’ immunological status. Conclusions: In AR, BOS and stable lung transplant, regulatory and effector cells clearly demonstrated different pathways of activation. Understanding of the balance of T cells and T and B regulatory cells can offers insights into rejection.
Inflammation Regulates the Multi-Step Process of Retinal Regeneration in Zebrafish
Authors: Nagashima Mikiko , Hitchcock Peter F.
Published: April 2021

The ability to regenerate tissues varies between species and between tissues within a species. Mammals have a limited ability to regenerate tissues, whereas zebrafish possess the ability to regenerate almost all tissues and organs, including fin, heart, kidney, brain, and retina. In the zebrafish brain, injury and cell death activate complex signaling networks that stimulate radial glia to reprogram into neural stem-like cells that repair the injury. In the retina, a popular model for investigating neuronal regeneration, Müller glia, radial glia unique to the retina, reprogram into stem-like cells and undergo a single asymmetric division to generate multi-potent retinal progenitors. Müller glia-derived progenitors then divide rapidly, numerically matching the magnitude of the cell death, and differentiate into the ablated neurons. Emerging evidence reveals that inflammation plays an essential role in this multi-step process of retinal regeneration. This review summarizes the current knowledge of the inflammatory events during retinal regeneration and highlights the mechanisms whereby inflammatory molecules regulate the quiescence and division of Müller glia, the proliferation of Müller glia-derived progenitors and the survival of regenerated neurons.
Reliability of Sonography Measures of the Lumbar Multifidus and Transversus Abdominis during Static and Dynamic Activities in Subjects with Non-Specific Chronic Low Back Pain
Authors: Sánchez Romero Eleuterio A. , Alonso Pérez José Luis , Muñoz Fernández Alberto Carlos , Battaglino Andrea , Castaldo Matteo , Cleland Joshua A. , Villafañe Jorge Hugo
Published: April 2021

Purpose: The purpose of this study was to investigate the test-retest reliability of ultrasound (US) thickness measurements and the muscle contraction ratio (CR) of lumbar multifidus (LM) and transversus abdominis (TA) muscles in participants with and without nonspecific chronic low back pain (NCLBP). Methods: A total of 62 participants (37 with NCLBP, 25 without NCLBP) with participated in the study. The within-day and between-day reliability of US thickness measurements and CR in a lying (supine for TA and prone for LM) and sitting positions for both muscles (sitting on a gym ball with both feet on the ground or lifting one foot off the floor) were assessed. Reliability analysis was performed with intraclass correlations (ICCs) for these two static and dynamic positions. Results: Test-retest reliability was calculated to be good to high for the static position (ICC = 0.72–0.95) and the dynamic position (ICC = 0.74–0.94) sonographic measurements in both group of TA measurement. Test-retest reliability of LM measurements was good to high for the static position (ICC = 0.82–0.95) and the dynamic position (ICC = 0.85–0.97) sonographic measurements in both groups. Conclusions: US imaging is a highly reliable method for the assessment of TA and LM thickness muscles in the dynamic position in participants with and without NCLBP. The CR measures may be adequately reliable in assessing the function of the TA and LM muscles in participants with NCLBP and healthy ones.
Preoperative Diagnosis Failure for a Rare Gastric Collision Tumor: A Case Report
Authors: Elshaer Rabie E. , Elgammal Eid R. , Elmistekawy Amr M. , Ghannam Walaa A. , Elshamy Ahmed E. , Abed Sally Y. , Zaitone Sawsan A.
Published: April 2021

Gastrointestinal stromal tumors (GISTs) are common mesenchymal tumors of the gastrointestinal tract (GIT), usually occur as a solitary neoplasm. Inflammatory florid polyp (IFP) is a solitary rare benign lesion of the gastrointestinal tract, mainly occur in the gastric antrum, whose atypical presentation can mimic GISTs or other malignant tumors, therefore the synchronous occurrence of GISTs and IFP is extremely rare. We had a case of a 58-year-old man that was presented with recurrent epigastric pain and recurrent melena. Upper endoscopic examination revealed a large polypoid antrum polyp measured 7 cm at greatest dimension with focal ulceration. Clinical and radiological features did not reach the definite diagnosis until histopathological evaluation with immunohistochemical analysis was performed. Surgical intervention is recommended and partial gastrectomy was done with wide resection margins. Histological examination revealed two distinct GISTs and IFP parts presenting a collision tumor that showed spindle and epitheloid cells consistent with GISTs with histological features of florid polyp showed a characteristic perivascular onion-skin arrangement of spindle cells with dense chronic inflammatory infiltrate including eosinophils and lymphocytes. Immunohistochemical studies have been done and revealed an association between GISTs and IFP. To the best of our knowledge, this is the first case of a collision tumor consisting of a GIST and an IFP arising in the stomach. In conclusion, the gastrointestinal stromal tumor is the comments mesenchymal tumor of GIT and IFP is a rare benign lesion of GIT therefore association between GIST and IFP as a collision tumor is extremely rare.
Comparison of Compressed Sensing and Gradient and Spin-Echo in Breath-Hold 3D MR Cholangiopancreatography: Qualitative and Quantitative Analysis
Authors: Jang Weon , Song Ji Soo , Kim Sang Heon , Yang Jae Do
Published: April 2021

While magnetic resonance cholangiopancreatography (MRCP) is routinely used, compressed sensing MRCP (CS-MRCP) and gradient and spin-echo MRCP (GRASE-MRCP) with breath-holding (BH) may allow sufficient image quality with shorter acquisition times. This study qualitatively and quantitatively compared BH-CS-MRCP and BH-GRASE-MRCP and evaluated their clinical effectiveness. Data from 59 consecutive patients who underwent both BH-CS-MRCP and BH-GRASE-MRCP were qualitatively analyzed using a five-point Likert-type scale. The signal-to-noise ratio (SNR) of the common bile duct (CBD), contrast-to-noise ratio (CNR) of the CBD and liver, and contrast ratio between periductal tissue and the CBD were measured. Paired t-test, Wilcoxon signed-rank test, and McNemar’s test were used for statistical analysis. No significant differences were found in overall image quality or duct visualization of the CBD, right and left 1st level intrahepatic duct (IHD), cystic duct, and proximal pancreatic duct (PD). BH-CS-MRCP demonstrated higher background suppression and better visualization of right (p = 0.004) and left 2nd level IHD (p < 0.001), mid PD (p = 0.003), and distal PD (p = 0.041). Image quality degradation was less with BH-GRASE-MRCP than BH-CS-MRCP (p = 0.025). Of 24 patients with communication between a cyst and the PD, 21 (87.5%) and 15 patients (62.5%) demonstrated such communication on BH-CS-MRCP and BH-GRASE-MRCP, respectively. SNR, contrast ratio, and CNR of BH-CS-MRCP were higher than BH-GRASE-MRCP (p < 0.001). Both BH-CS-MRCP and BH-GRASE-MRCP are useful imaging methods with sufficient image quality. Each method has advantages, such as better visualization of small ducts with BH-CS-MRCP and greater time saving with BH-GRASE-MRCP. These differences allow diverse choices for visualization of the pancreaticobiliary tree in clinical practice.
Optical Coherence Tomography of Plaque Erosion and Thrombus in Severe Vertebral Artery Stenosis
Authors: Yan Lin , Dmytriw Adam A. , Yang Bin , Jiao Liqun
Published: April 2021

A 69-year-old male presented with medically refractory vertebrobasilar insufficiency and paroxysmal subjective dizziness for six months. Severe stenosis of a dominant left V2 vertebral artery segment was identified on digital subtraction angiography (DSA) with an irregular intraluminal filling defect immediately above the stenosis. Optical coherence tomography (OCT) demonstrated a normal lumen at the distal end, with red thrombus detected distal to the stenosis. Atherosclerotic plaque containing fibro-lipid was also identified and treated with a drug-eluting stent. Distal red thrombi were not covered by stenting, indicating embolization risk in the future. Clear posterior fossa symptoms occurred after intervention, and treatment with a standard dual antiplatelet regimen and statin therapy was prescribed for one year. Six months after treatment, the symptoms improved, and six-minute walking distances were successful with no gait impairment. To our knowledge, this is the first V2 segment stenosis assessed by OCT imaging before and after stenting, indicating an intact fibrous cap with thrombus formation, as well as plaque erosion. Understanding the role and careful use of OCT may improve the identification of red thrombus and plaque erosion when clinically indicated.
Nephrotoxicity of Anti-Angiogenic Therapies
Authors: Van Wynsberghe Margaux , Flejeo Joanne , Sakhi Hamza , Ollero Mario , Sahali Dil , Izzedine Hassan , Henique Carole
Published: April 2021

The use of inhibitors of vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor 2 (VEGFR2) signaling for the treatment of cancer has increased over the last decade. This signaling pathway plays a fundamental role in angiogenesis and also in kidney physiology. The emergence of anti-angiogenic therapies has led to adverse nephrotoxic effects, despite improving the outcomes of patients. In this review, we will present the different anti-angiogenic therapies targeting the VEGFR pathway in association with the incidence of renal manifestations during their use. In addition, we will discuss, in detail, the pathophysiological mechanisms of frequent renal diseases such as hypertension, proteinuria, renal dysfunction, and electrolyte disorders. Finally, we will outline the cellular damage described following these therapies.
Monitoring of B Cell in Kidney Transplantation: Development of a Novel Clusters Analysis and Role of Transitional B Cells in Transplant Outcome
Authors: Alfaro Rafael , Legaz Isabel , González-Martínez Gema , Jimenez-Coll Víctor , Martínez-Banaclocha Helios , Galián José Antonio , Botella Carmen , de la Peña-Moral Jesús , Moya-Quiles María Rosa , Campillo José Antonio , Minguela Alfredo , Llorente Santiago , Muro Manuel
Published: April 2021

Background: B lymphocytes (BL) seem to play an important role in transplantation, although the and role of different subpopulations in monitoring and outcome is not clear. Our aim was to monitoring immunological profiles based on BL subpopulations in kidney recipients (KR) with the risk of acute rejection (AR). Methods: Monitoring of BL subpopulations was performed by flow cytometry in PBLs before transplantation and three and six months after transplantation (PTX). We used two methodological approaches, a traditional analysis, and a novel cluster analysis, to determine the association between BL subpopulations, AR incidence, and graft function. Results: After three months of PTX, KRs with a B phenotype enriched in transitional BL and plasmablasts had better kidney function and lower AR incidence. KRs with decreased transitional BL and plasmablasts were associated with lower kidney function and higher AR PTX. KRs that had an increase in transitional BL PTX had a better clinical outcome. The increase in transitory BL during PTX was also associated with an increase in Tregs. Indeed, KRs receiving thymoglobulin as induction therapy showed a slight decrease in the relative frequency of naive BLs after three months of PTX. Conclusion: The monitoring of BL subpopulations may serve as a non-invasive tool to improve immunological follow-up of patients after kidney transplantation. However, further studies are needed to confirm the obtained results, define cut-off values, and standardize more optimal and even custom/customized protocols.
A Case Study of Educational Games in Virtual Reality as a Teaching Method of Lean Management
Authors: Krajčovič Martin , Gabajová Gabriela , Furmannová Beáta , Vavrík Vladimír , Gašo Martin , Matys Marián
Published: April 2021

(1) At present, it is important to bring the latest technologies from industrial practice into the teaching process of educational institutions, including universities. The presented case study addresses the application of educational games in virtual reality to the teaching process in a university environment. (2) The study took place at the Department of Industrial Engineering of the University of Žilina in Žilina and consisted of two phases. In the first phase, students’ satisfaction with current teaching methods was examined. The second phase focused on an educational game in virtual reality, which introduced a non-traditional approach for teaching lean management, namely the tool 5S. (3) This game was designed by the study authors and created in the Godot game engine. The educational game was provided to students during class. After completing the game, participants were asked to fill out a questionnaire. The aim was to enable students to express their opinion on the educational game and to identify the main benefits of this approach in the teaching process. (4) In the study’s final phase, based on the acquired knowledge, the authors examined the benefits and disadvantages of virtual reality educational games for the teaching process of industrial engineering tools.
Slip Estimation and Compensation Control of Omnidirectional Wheeled Automated Guided Vehicle
Authors: Chen Pei-Jarn , Yang Szu-Yueh , Chen Yen-Pei , Muslikhin Muslikhin , Wang Ming-Shyan
Published: April 2021

To achieve Industry 4.0 solutions for the networking of mechatronic components in production plants, the use of Internet of Things (IoT) technology is the optimal way for goods transportation in the cyber-physical system (CPS). As a result, automated guided vehicles (AGVs) are networked to all other participants in the production system to accept and execute transport jobs. Accurately tracking the planned paths of AGVs is therefore essential. The omnidirectional mobile vehicle has shown its excellent characteristics in crowded environments and narrow aisle spaces. However, the slip problem of the omnidirectional mobile vehicle is more serious than that of the general wheeled mobile vehicle. This paper proposes a slip estimation and compensation control method for an omnidirectional Mecanum-wheeled automated guided vehicle (OMWAGV) and implements a control system. Based on the slip estimation and compensation control of the general wheeled mobile platform, a Microchip dsPIC30F6010A microcontroller-based system uses an MPU-9250 multi-axis accelerometer sensor to derive the longitudinal speed, transverse speed, and steering angle of the omnidirectional wheel platform. These data are then compared with those from the motor encoders. A linear regression with a recursive least squares (RLS) method is utilized to estimate real-time slip ratio variations of four driving wheels and conduct the corresponding compensation and control. As a result, the driving speeds of the four omnidirectional wheels are dynamically adjusted so that the OMWAGV can accurately follow the predetermined motion trajectory. The experimental results of diagonally moving and cross-walking motions without and with slip estimation and compensation control showed that, without calculating the errors occurred during travel, the distances between the original starting position to the stopping position are dramatically reduced from 1.52 m to 0.03 m and from 1.56 m to 0.03 m, respectively. The higher tracking accuracy of the proposed method verifies its effectiveness and validness.
An Empirical Study of Korean Sentence Representation with Various Tokenizations
Authors: Cho Danbi , Lee Hyunyoung , Kang Seungshik
Published: April 2021

It is important how the token unit is defined in a sentence in natural language process tasks, such as text classification, machine translation, and generation. Many studies recently utilized the subword tokenization in language models such as BERT, KoBERT, and ALBERT. Although these language models achieved state-of-the-art results in various NLP tasks, it is not clear whether the subword tokenization is the best token unit for Korean sentence embedding. Thus, we carried out sentence embedding based on word, morpheme, subword, and submorpheme, respectively, on Korean sentiment analysis. We explored the two-sentence representation methods for sentence embedding: considering the order of tokens in a sentence and not considering the order. While inputting a sentence, which is decomposed by token unit, to the two-sentence representation methods, we construct the sentence embedding with various tokenizations to find the most effective token unit for Korean sentence embedding. In our work, we confirmed: the robustness of the subword unit for out-of-vocabulary (OOV) problems compared to other token units, the disadvantage of replacing whitespace with a particular symbol in the sentiment analysis task, and that the optimal vocabulary size is 16K in subword and submorpheme tokenization. We empirically noticed that the subword, which was tokenized by a vocabulary size of 16K without replacement of whitespace, was the most effective for sentence embedding on the Korean sentiment analysis task.
A Review on Additive Manufacturing Possibilities for Electrical Machines
Authors: Naseer Muhammad Usman , Kallaste Ants , Asad Bilal , Vaimann Toomas , Rassõlkin Anton
Published: April 2021

This paper presents current research trends and prospects of utilizing additive manufacturing (AM) techniques to manufacture electrical machines. Modern-day machine applications require extraordinary performance parameters such as high power-density, integrated functionalities, improved thermal, mechanical & electromagnetic properties. AM offers a higher degree of design flexibility to achieve these performance parameters, which is impossible to realize through conventional manufacturing techniques. AM has a lot to offer in every aspect of machine fabrication, such that from size/weight reduction to the realization of complex geometric designs. However, some practical limitations of existing AM techniques restrict their utilization in large scale production industry. The introduction of three-dimensional asymmetry in machine design is an aspect that can be exploited most with the prevalent level of research in AM. In order to take one step further towards the enablement of large-scale production of AM-built electrical machines, this paper also discusses some machine types which can best utilize existing developments in the field of AM.
Understanding of Construction Product Assessment Issues and Sustainability among Investors, Architects, Contractors, and Sellers of Construction Products in Poland
Authors: Michalak Jacek , Michałowski Bartosz
Published: April 2021

The building sector is one of the most critical branches of the economy influencing global warming today. Following the European Union’s Construction Products Regulation (CPR), the sustainable use of natural resources in construction is one of the seven basic buildings’ requirements. However, due to the lack of provisions in this regard, construction products are not yet subject to mandatory assessment and verification of the constancy of performance in this area. The paper presents the research results with the participation of 842 respondents who are investors, architects, contractors, and sellers of building materials. The analysis of their perceptions of issues related to the term sustainable development and knowledge of selected documents functioning in construction is presented. The share of people who correctly assigned the term sustainable development to equal treatment of environmental protection, economic development, and social development ranged between 52.5% and 65.7%. Knowledge of people associated with construction about the role of the declaration of performance (DoP) of construction products is high (from 73.9% to 99.4% correct answers). For Environmental Product Declaration (EPD), lower knowledge of this document’s role was noted, from 24.1% to 56.5% of correct answers. The obtained results indicate the need for further education.
Analysis and Design of a Multi-Port DC-DC Converter for Interfacing PV Systems
Authors: Alajmi Bader N. , Marei Mostafa I. , Abdelsalam Ibrahim , AlHajri Mohamed F.
Published: April 2021

A high-frequency multi-port (HFMP) direct current (DC) to DC converter is presented. The proposed HFMP is utilized to interface a photovoltaic (PV) system. The presented HFMP is compact and can perform maximum power point tracking. It consists of a high-frequency transformer with many identical input windings and one output winding. Each input winding is connected to a PV module through an H-bridge inverter, and the maximum PV power is tracked using the perturb and observe (P&O) technique. The output winding is connected to a DC bus through a rectifier. The detailed analysis and operation of the proposed HFMP DC-DC converter are presented. Extensive numerical simulations are conducted, using power system computer aided design (PSCAD)/electromagnetic transients including DC (EMTDC) software, to evaluate the operation and dynamic behavior of the proposed PV interfacing scheme. In addition, an experimental setup is built to verify the performance of the HFMP DC-DC converter.
Flexible Transmission Network Expansion Planning Based on DQN Algorithm
Authors: Wang Yuhong , Chen Lei , Zhou Hong , Zhou Xu , Zheng Zongsheng , Zeng Qi , Jiang Li , Lu Liang
Published: April 2021

Compared with static transmission network expansion planning (TNEP), multi-stage TNEP is more in line with the actual situation, but the modeling is also more complicated. This paper proposes a new multi-stage TNEP method based on the deep Q-network (DQN) algorithm, which can solve the multi-stage TNEP problem based on a static TNEP model. The main purpose of this research is to provide grid planners with a simple and effective multi-stage TNEP method, which is able to flexibly adjust the network expansion scheme without replanning. The proposed method takes into account the construction sequence of lines in the planning and completes the adaptive planning of lines by utilizing the interactive learning characteristics of the DQN algorithm. In order to speed up the learning efficiency of the algorithm and enable the agent to have a better judgment on the reward of the line-building action, the prioritized experience replay (PER) strategy is added to the DQN algorithm. In addition, the economy, reliability, and flexibility of the expansion scheme are considered in order to evaluate the scheme more comprehensively. The fault severity of equipment is considered on the basis of the Monte Carlo method to obtain a more comprehensive system state simulation. Finally, extensive studies are conducted with IEEE 24-bus reliability test system, and the computational results demonstrate the effectiveness and adaptability of the proposed flexible TNEP method.
Achieving High-Performance Spherical Natural Graphite Anode through a Modified Carbon Coating for Lithium-Ion Batteries
Authors: Kwon Hae-Jun , Woo Sang-Wook , Lee Yong-Ju , Kim Je-Young , Lee Sung-Man
Published: April 2021

The electrochemical performance of modified natural graphite (MNG) and artificial graphite (AG) was investigated as a function of electrode density ranging from 1.55 to 1.7 g∙cm−3. The best performance was obtained at 1.55 g∙cm−3 and 1.60 g∙cm−3 for the AG and MNG electrodes, respectively. Both AG, at a density of 1.55 g∙cm−3, and MNG, at a density of 1.60 g∙cm−3, showed quite similar performance with regard to cycling stability and coulombic efficiency during cycling at 30 and 45 °C, while the MNG electrodes at a density of 1.60 g∙cm−3 and 1.7 g∙cm−3 showed better rate performance than the AG electrodes at a density of 1.55 g∙cm−3. The superior rate capability of MNG electrodes can be explained by the following effects: first, their spherical morphology and higher electrode density led to enhanced electrical conductivity. Second, for the MNG sample, favorable electrode tortuosity was retained and thus Li+ transport in the electrode pore was not significantly affected, even at high electrode densities of 1.60 g∙cm−3 and 1.7 g∙cm−3. MNG electrodes also exhibited a similar electrochemical swelling behavior to the AG electrodes.
Assessment of Molecular Additives on the Lifetime of Carbon-Based Mesoporous Perovskite Solar Cells
Authors: López-Vicente Rodolfo , Abad José , Padilla Javier , Urbina Antonio
Published: April 2021

Perovskite solar cells have progressed very steadily, reaching power conversion efficiencies (PCE) beyond 20% while also improving their lifetimes up to 10,000 h. A large number of cell architecture and materials for active, transporting and electrode layers have been used, either in blends or in nanostructured layers. In this article, a set of perovskite solar cells have been designed, fabricated and characterized with special focus on their lifetime extension. The inclusion of 5-amino-valeric acid iodide (5–AVAI) as interlayer in a methyl-amino lead-iodide (MAPI) perovskite solar cell has provided additional stability in cells with PCE > 10% and T80 = 550 h. Experiments for up to 1000 h with solar cells at maximum power point under continuous illumination with solar simulator have been carried out (1 kW/m2, AM1.5G, equivalent to more than six months of outdoor illumination in locations such as Southeast Spain, with an average irradiation of 1900 kWh/m2/year). The addition of molecular additives in the bulk active layer and ETL and carbon layers not only allows better carrier transport, but also increases the stability of the perovskite solar cell by reducing ion migration within the bulk MAPI and between the different layers. Engineered interfaces with ZrO2 between the TiO2 and carbon layers contribute to reducing degradation.