bluuebunny/crossref_metadata_2025 huggingface dataset:
The AlfaCrux CubeSat Mission Description and Early Results
Authors: Borges Renato Alves , dos Santos Andrea Cristina , Silva William Reis , Aguayo Leonardo , Borges Geovany Araújo , Karam Marcelo Monte , de Sousa Rogério Baptista , García Bibiano Fernández-Arruti , Botelho Vitor Manuel de Sousa , Fernández-Carrillo José Manuel , Lago Agra José Miguel , Agelet Fernando Aguado , Borges João Vítor Quintiliano Silvério , de Oliveira Alexandre Crepory Abbott , de Mello Bruno Tunes , Avelino Yasmin da Costa Ferreira , Modesto Vinícius Fraga , Brenag Emanuel Couto
Published: September 2022

On 1 April 2022, the AlfaCrux CubeSat was launched by the Falcon 9 Transporter-4 mission, the fourth SpaceX dedicated smallsat rideshare program mission, from Space Launch Complex 40 at Cape Canaveral Space Force Station in Florida into a Sun-synchronous orbit at 500 km. AlfaCrux is an amateur radio and educational mission to provide learning and scientific benefits in the context of small satellite missions. It is an opportunity for theoretical and practical learning about the technical management, systems design, communication, orbital mechanics, development, integration, and operation of small satellites. The AlfaCrux payload, a software-defined radio hardware, is responsible for two main services, which are a digital packet repeater and a store-and-forward system. In the ground segment, a cloud-computing-based command and control station has been developed, together with an open access online platform to access and visualize the main information of the AlfaCrux telemetry and user data and experiments. It also becomes an in-orbit database reference to be used for different studies concerned with, for instance, radio propagation, attitude reconstruction, data-driven calibration algorithms for satellite sensors, among others. In this context, this paper describes the AlfaCrux mission, its main subsystems, and the achievements obtained in the early orbit phase. Scientific and engineering assessments conducted with the spacecraft operations to tackle unexpected behaviors in the ground station and also to better understand the space environment are also presented and discussed.
Improvement of Dust Particle Suction Efficiency by Controlling the Airflow of a Regenerative Air Sweeper
Authors: Fayzullayevich Jamshid Valiev , Tan Gangfeng , Alex Frimpong J. , Agyeman Philip K. , Wu Yongjia
Published: September 2022

In a regenerative air sweeper, airflow and dust particles entering the system are filtered and recirculated within the system. The uncirculated portion of the exhaust air in the system spreads to the ambient air, and PM2.5 dust in the air can poison the environment and adversely affect human health. The development of an airflow control system to reduce road dust emissions and improve air quality was the main contribution of this study. A regenerative air sweeper airflow control system is designed to direct the air from the centrifugal fan back into the pickup head to fully absorb the dust particles and balance the positive and negative air pressures inside the pickup head. The modeling and analysis of the dust control system were performed using an experimental test rig system. A mathematical model of the fundamental parameters of the regenerative air sweeper and dust control system was established. Computational fluid dynamics (CFD) ANSYS was used for the analysis to determine the direction of airflow via the suction and inlet ducts. The discrete particle model (DPM) accurately predicted particle trajectories and measured the suction efficiency of particles of different shapes and types. By controlling the circulating harmful air flow in the system, the amount of PM2.5 released into the atmosphere was reduced by 90%. The suction efficiency of the 200 μm sized sand particles was higher than 95%. The results provide theoretical and methodological assistance for the development of improved road sweeper dust control systems.
A New Approach to Machine Learning Model Development for Prediction of Concrete Fatigue Life under Uniaxial Compression
Authors: Son Jaeho , Yang Sungchul
Published: September 2022

The goal of this work is to show how machine learning models, such as the random forest, neural network, gradient boosting, and AdaBoost models, can be used to forecast the fatigue life (N) of plain concrete under uniaxial compression. Here, we developed our final machine learning model by generating the following three data files from the original data used in the work of Zhang et al.: (a) grouped data with the same input variable value and different output variable logN value, (b) data excluding outliers selected by three or more outlier detection methods; (c) average data excluding outliers, created by averaging the grouped data after excluding outliers from among the grouped data. Excluding the sustained strength of the concrete variable, originally treated as the seventh input variable in the work of Zhang et al., resulted in improving the determination coefficient (R2) values. Moreover, the gradient boosting model showed a high R2 value at 0.753, indicating a high accuracy in predicting outcomes. Further analysis using data excluding outliers shows that the R2 value increased to 0.803. Moreover, the average data excluding outliers provided the best R2 value at 0.915. Finally, a permutation feature importance (PFI) analysis was carried out to determine the strength of the relationship between the feature and the target value for the gradient boosting model. The analysis results showed that the maximum stress level (Smax) and loading frequency (f) were the most significant input variables, followed by compressive strength (f′c) and maximum to minimum stress ratio (R). Shape and height to width ratio (h/w) were the features with a non-significant influence on the model. This trend was previously confirmed by a Pearson and Spearman correlation analysis.
How to Isolate Non-Public Networks in B5G: A Review
Authors: Sun Qian , Hui Ning , Zhou Yiqing , Tian Lin , Zeng Jie , Ge Xiaohu
Published: September 2022

Non-public networks (NPNs) have drawn much attention due to their flexibility and efficiency with B5G. According to the requirements of various application scenarios, NPNs can be tailored to a number of deployments, sharing the B5G system totally or in part. The isolation of NPNs is a critical issue. This paper provides a survey of isolation schemes for B5G NPNs. First, we present an overview of various deployments and the corresponding isolation demands for B5G NPNs. To meet these isolation demands, three kinds of NPN isolation—i.e., spectrum isolation, RAN isolation and CN isolation—are discussed. Then, the corresponding isolation technologies are introduced and analyzed. Finally, open research challenges, such as wireless throughput capacity with spectrum isolation, operation with isolation requirements and data isolation of software-defined CN for B5G NPNs, are discussed.
Temporal and Spatial Variation Characteristics of Actual Evapotranspiration in the Yiluo River Basin Based on the Priestley–Taylor Jet Propulsion Laboratory Model
Authors: Ling Minhua , Yang Yuanqing , Xu Chenyang , Yu Lili , Xia Qinyuan , Guo Xiaomin
Published: September 2022

Evapotranspiration is an important part of the hydrological cycle, affecting the terrestrial hydrological process and the relationship between water resource transformation. Analyzing and mastering the temporal and spatial variations in evapotranspiration are of great significance for the rational development, utilization, and protection of water resources in the basin. Based on MODIS remote sensing data and combined with meteorological and hydrological data, the PT-JPL model was used to estimate the actual evapotranspiration of the Yiluo River Basin, and the applicability of the PT-JPL model for estimating actual evapotranspiration in the basin was analyzed. The spatial and temporal characteristics of actual evapotranspiration in the Yiluo River Basin were analyzed, and the correlation between actual evapotranspiration in the basin and influencing factors such as precipitation, temperature, and vegetation was explored. The main conclusions are as follows: the PT-JPL model has good applicability in the Yiluo River Basin; the total actual evapotranspiration in the basin showed a decreasing trend, which was consistent with the trend of precipitation, indicating that the actual evapotranspiration may be limited by water conditions in the study area. The evapotranspiration of the basin was higher in the upstream and lower in the downstream, which may be related to the better vegetation coverage in the upper basin than in the downstream. As an important indicator of vegetation change, NDVI showed a good correlation with evapotranspiration, which also verified this. In addition, the correlation between evapotranspiration and temperature was also good.
Gamification Techniques and Best Practices in Computerized Working Memory Training: A Systematic Literature Review
Authors: Chaldogeridis Agisilaos , Tsiatsos Thrasyvoulos
Published: September 2022

Computerized Cognitive Training (CCT) programs have been widely used in the past decades, offering an alternative solution in enhancing cognitive functionalities, especially Working Memory (WM). CCT supports users to overcome the monotonous context of training by utilizing specific game elements (GE). Several previous studies focused on the efficacy of CCT, but only a few examined their potential in increasing motivation and adherence. This study aimed to (a) conduct a state-of-the-art systematic literature review to identify the most commonly used GEs in WM training and assessment; and to (b) investigate how they are utilized in regard to the audiences that are being applied. In total, seven online databases were searched using keywords related to WM and CCT, targeting studies from 2015 until early 2022. The systematic review identified 44 studies which were eligible for inclusion. The results report that the most widely used GEs are conflict (88.63%), feedback (84.9%), difficulty adjustment (73%), action points and levels (70.45%). On the other hand, GEs associated with competition and cooperation are not preferred except in very few cases. In conclusion, there is common ground in the use of GEs for WM training, but there is a need for further research to compare the GEs between them.
A Validated HPLC Multichannel DAD Method for the Simultaneous Determination of Amoxicillin and Doxycycline in Pharmaceutical Formulations and Wastewater Samples
Authors: Becze Anca , Resz Maria-Alexandra , Ilea Aranka , Cadar Oana
Published: September 2022

The quality of marketed pharmaceutical formulations must be guaranteed to attain better remedial effects and lower toxicity. The wide exploitation of antibiotics may lead to their presence as residues in body fluids and wastewaters, potentially toxic to human health. Consequently, determining antibiotics in pharmaceutical formulations and water samples is of significant importance. This paper aims to explore the possibilities of a high-performance liquid chromatography coupled with diode array detection (HPLC-DAD) method to obtain a simple, fast, and efficient analytical tool for the simultaneous determination of antibiotics in pharmaceutical formulations and environmental samples. The method was completely validated with regard to specificity, linearity, detection and quantification limits, precision, accuracy, and robustness according to the requirements of existing guidelines, and was proven to be reliable and suitable for the envisioned application. The linearity study was conducted for the calibration curves in the range of 10–100 μg/mL. The limits of detection and quantification were found to be 0.2 and 0.7 μg/mL for amoxicillin and 0.3 and 1.0 μg/mL for doxycycline, respectively. The high recovery of drugs from their commercial pharmaceutical formulations (93%) and from wastewater samples (98%) indicated good accuracy and precision. The method is robust for small or deliberate changes to the chromatographic parameters, and it was successfully applied for the quantitative determination of amoxicillin and doxycycline in wastewater and commercial tablets. The obtained results proved that the validated method is appropriate for its intended use in the routine quality control and assay of both antibiotics studied.
Learning Embedding for Signed Network in Social Media with Hierarchical Graph Pooling
Authors: Chen Jiawang , Wu Zhenqiang
Published: September 2022

Signed network embedding concentrates on learning fixed-length representations for nodes in signed networks with positive and negative links, which contributes to many downstream tasks in social media, such as link prediction. However, most signed network embedding approaches neglect hierarchical graph pooling in the networks, limiting the capacity to learn genuine signed graph topology. To overcome this limitation, this paper presents a unique deep learning-based Signed network embedding model with Hierarchical Graph Pooling (SHGP). To be more explicit, a hierarchical pooling mechanism has been developed to encode the high-level features of the networks. Moreover, a graph convolution layer is introduced to aggregate both positive and negative information from neighbor nodes, and the concatenation of two parts generates the final embedding of the nodes. Extensive experiments on three large real-world signed network datasets demonstrate the effectiveness and excellence of the proposed method.
Comparison of Three DNA Extraction Kits for Assessment of Bacterial Diversity in Activated Sludge, Biofilm, and Anaerobic Digestate
Authors: Florczyk Maciej , Cydzik-Kwiatkowska Agnieszka , Ziembinska-Buczynska Aleksandra , Ciesielski Slawomir
Published: September 2022

Direct DNA analysis is the most widely used approach for microorganism characterization in natural and built environments; therefore, reliable and effective methods of nucleic acid extraction for samples from particular types of environments are needed. In this study, we compared three commercial kits for metagenomic DNA extraction from three types of biomass: activated sludge, biofilm, and anaerobic digestate. The yield, purity, and quality of DNA were measured, and the effect that the DNA kit had on the subsequent microbial community analysis was assessed with amplified ribosomal intergenic spacer analysis (ARISA). Amplicons were analyzed automatically utilizing capillary electrophoresis. For the activated sludge and digestate, the suggested kit is FastDNA™ Spin Kit for Soil (MP Biomedicals). This kit allowed the highest DNA yield to be obtained and provided the highest biodiversity. For biofilm with a high content of extracellular polymeric substances, the FavorPrep™ Soil DNA Isolation Mini Kit (FAVORGEN) is recommended. This kit allowed to obtain the highest biodiversity and provided the most reliable results of genetic distance assessment in this type of biomass.
Isolation, Propagation and Genotyping of Human Rotaviruses Circulating among Children with Gastroenteritis in Two Egyptian University Hospitals
Authors: El-Gayar Mona H. , Saleh Sarra E. , Mohamed Aly F. , Aboulwafa Mohammad M. , Hassouna Nadia A. , Allayeh Abdou Kamal
Published: September 2022

The most prevalent cause of infectious neonatal diarrhea is Group A rotavirus (RVA). Unfortunately, there is a dearth of data on the incidence of rotavirus-associated infections among Egyptian children. The present study aimed to isolate, propagate, and genotype human rotaviruses circulating among Egyptian children with acute gastroenteritis admitted to two main university pediatric hospitals, Abo El-Reesh and El-Demerdash, over two consecutive winters, 2018–2020. Diarrheal samples (n = 230) were screened for Group A rotavirus RNA using RT-PCR assay. In positive samples (n = 34), multiplex semi-nested PCR was utilized to determine G and P genotypes. Thirty-four (14.8%) of the collected samples tested positive. The genotype distribution revealed that G1P[8] was the predominant rotavirus genotype throughout the current study. All rotavirus-positive fecal samples were passaged twice on human colorectal adenocarcinoma cell line (Caco-2) and rhesus monkey kidney epithelial cell line (MA104). Both cell lines could successfully isolate 14.7% (n = 5 out of 34) of the identified strains; however, Caco-2 cell line was shown to be more efficient than MA104 in promoting the propagation of human rotaviruses identified in Egyptian children’s feces.
Production of Biodiesel from Underutilized Algae Oil: Prospects and Current Challenges Encountered in Developing Countries
Authors: Adewuyi Adewale
Published: September 2022

Biofuel continues to thrive as an outstanding source of renewable energy for the global community. Several resources have been proposed as sources of feedstocks for biofuel; however, some of these have shortcoming. The use of biomass such as algae as a source of feedstock for biofuel is undoubtedly sustainable and green. Unfortunately, the use of algae oil for biodiesel production is underutilized in developing countries. Therefore, this study focuses on finding a better understanding of the evolving prospects and current challenges facing biodiesel production from algae oil in developing countries. The study revealed that less attention is given to the use of algae oil in biodiesel production due to poor enlightenment on biotechnology, high poverty rates, government policies, business strategies, and poor funding of research. Interestingly, several species of algae that can serve as sustainable feedstocks for biodiesel production have been identified in developing countries. It is evident that algae oil has properties that qualify it for the production of biodiesel with fuel properties that meet both the American Society for Testing and Materials and the European standards for biodiesel.
Evolution of Quantitative Optical Coherence Tomography Angiography Markers with Glycemic Control: A Pilot Study
Authors: Ruiz Thibault , Dutour Anne , Denis Danièle , Comet Alban , Eisinger Martin , Houssays Marie , Darmon Patrice , Boullu Sandrine , Soghomonian Astrid , David Thierry , Gaborit Bénédicte , Gascon Pierre
Published: September 2022

Aim: We aimed to analyze changes in retinal microvascularization with intensive reduction of glycated hemoglobin A1c (HbA1c) in patients with poorly controlled diabetes using quantitative optical coherence tomography angiography (OCT-A) metrics. Method: This was a retrospective observational study in patients with uncontrolled diabetes admitted to the hospital for glycemic control. A second set of 15 healthy volunteers was included to serve as a control group. OCT-A was performed at inclusion and at 3 months to measure foveal avascular zone area (FAZA), vessel density (VD) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP), acircularity index (AI), and fractal dimension (FD). Results: This analysis included 35 patients (35 eyes): 28 type-2 diabetics and 7 type-1 diabetics. Mean HbA1c was 13.1 ± 2.0% at inclusion and 7.0 ± 1.5% at 3 months. In the short period from inclusion to 3 months post-inclusion, patients showed significant decrease in VD–DCP (28.8% vs. 27.8%; p = 0.014), a significant increase in FAZA (0.300 mm2 vs. 0.310 mm2; p < 0.001), and a significant increase in AI (1.31 vs. 1.34; p < 0.01). Multivariate analysis found an increase in FAZA was correlated with baseline HbA1c level and age (R2 = 0.330), and a decrease in VD-DCP was correlated with HbA1c decrease and diabetes duration (R2 = 0.286). Conclusions: Rapid glycemic control in patients with uncontrolled diabetes led to possible short-term microvascular damage that correlated to both initial and decreased HbA1c.
Comparison of Short-Term Surgical Outcomes According to Immediately Postoperative Serum Glucose Level in Non-Diabetic Pancreatic Resection Patients
Authors: Lee Okjoo , Lim Chang-Sup , Yoon So Jeong , Jung Ji Hye , Shin Sang Hyun , Heo Jin Seok , Shin Yong Chan , Jung Woohyun , Han In Woong
Published: September 2022

The adequate regulation of postoperative serum glucose level (SGL) is widely accepted; however, the effects for non-diabetic patients who underwent major pancreatic surgery have not yet been established. We discerned the relevance of the immediately postoperative SGL to short-term postoperative outcomes from major pancreatic surgery in non-diabetic patients. Between January 2007 and December 2016, 2259 non-diabetic patients underwent major pancreatic surgery at four tertiary medical centers in Republic of Korea. Based on a SGL of 200 mg/dL, patients were classified into two groups by averaging the results of four SGL tests taken on the first day after surgery, and their short-term postoperative outcomes were analyzed. A 1:1 propensity score matching method was conducted to establish the high SGL group (n = 568) and the normal SGL group (n = 568). The high SGL group experienced a significantly higher rate of level C complications in the Clavien-Dindo classification (CDc) than the normal SGL group (24.1% vs. 16.5%, p = 0.002). Additionally, an SGL of more than 200 mg/dL was associated with a significantly high risk of complications above level C CDc after adjusting for other risk factors (hazard ratio = 1.324, 95% confidence interval = 1.048–1.672, p = 0.019). The regulation of SGL of less than 200 mg/dL in non-diabetic patients early after major pancreatic surgery could be helpful for reducing postoperative complications.
Prognostic Relevance of NPM1 and FLT3 Mutations in Acute Myeloid Leukaemia, Longterm Follow-Up—A Single Center Experience
Authors: Borlenghi Erika , Cattaneo Chiara , Bertoli Diego , Cerqui Elisa , Archetti Silvana , Passi Angela , Oberti Margherita , Zollner Tatiana , Giupponi Carlotta , Pagani Chiara , Bianchetti Nicola , Bottelli Chiara , Bagnasco Samuele , Sciumè Margherita , Tucci Alessandra , Rossi Giuseppe
Published: September 2022

The prognosis of acute myeloid leukemia depends on genetic aberrations, particularly NPM1 and FLT3-ITD mutations. The targeted drugs’ availability has renewed interest in FLT3 mutations, but the impact of these genetic alterations using these treatments is yet to be confirmed. Our objective was to evaluate the results obtained with the intensified NILG-AML 01/00 protocol (ClinicalTrials.gov Identifier: NCT 00400673) in 171 unselected patients (median age, 54.5 years, range 15–74) carrying the FLT3 (ITD or TKD) and/or NPM1 mutations. The CR rate and 5-y survival were 88.3% and 58% +/− 4, respectively, significantly higher in the NPM1-mutated (CR 93.9%, p: 0.0001; survival 71% +/− 6, p: 0.0017, respectively). In isolated ITD patients, the CR was lower (66.7%, p: 0.0009), and the 3 years-relapse-free survival worse (24%, p: <0.0002). The presence of ITD, irrespective of the allelic ratio, or TKD mutation, did not significantly affect the survival or relapse-free survival among the NPM1-co-mutated patients. Our data indicate that a high dose of ARAC plus idarubicin consolidation exerts a strong anti-leukemic effect in NPM1-mutated patients both with the FLT3 wild-type and mutated AML, while in the NPM1 wild-type and FLT3-mutated, the therapeutic effect remains unsatisfactory. New strategies incorporating target therapy with second-generation inhibitors will improve these results and their addition to this aggressive chemotherapeutic program merits testing.
Histone Deacetylase 3 Governs β-Estradiol-ERα-Involved Endometrial Tumorigenesis via Inhibition of STING Transcription
Authors: Chen Guofang , Yan Qiang , Liu Lin , Wen Xinyue , Zeng Hongliang , Yin Shasha
Published: September 2022

Purpose: The stimulator of interferon genes (STING) pathway plays a crucial role in antitumor immunity, and it is strictly regulated by many types of post-translational modifications. However, the contribution of acetylation involved in the regulation of STING to endometrial tumorigenesis remains unclear. Methods: We attempted to identify the key role of STING in endometrial carcinoma (EC) tissue and cell lines and explore its epigenetic regulation mechanism by HDACs that are critically involved in EC. We used IHC and qRT-PCR to detect the protein level and mRNA level of STING expression in endometrial carcinoma tissues, then explored the potential role of STING in tumor proliferation and apoptosis by CCK8 and flow cytometry, and identified the STING effect in the tumorigenicity by a mouse xenograft assay. We explored the possible relationship of acetylation alteration in STING regulation by ChIP analysis and Co-IP, and we knocked out STING in ECC1 and Ishikawa cells using CRISPR-Cas9 to further confirm the critical role of STING restoration induced by HDAC3 inhibitor RGFP-966 in the proliferation and apoptosis. Results: We found that STING expression was largely decreased and worked as an important regulator of cell proliferation and apoptosis; either activated or overexpressed STING, with both pharmacological and genetic approaches, largely blocked cell proliferation and induced apoptosis in EC. Moreover, STING expression was deregulated by both β-estradiol and HDAC3. Mechanically, we determined that HDAC3 can interact with β-estradiol-ERα and induce deacetylation of histone 3 lysine 4 at the STING promoter, thereby decreasing STING expression. Inhibition of HDAC3 increased STING expression, thereby inhibiting tumorigenesis. Conclusion: This study reveals a novel molecular mechanism by which HDAC3 inhibits STING transcription via β-estradiol-ERα and provides a promising therapy (a combination of HDAC and STING) for combating endometrial cancer.
Combined BRCA2 and MAGEC3 Expression Predict Outcome in Advanced Ovarian Cancers
Authors: Omole Emmanuel B. , Aijaz Iqbal , Ellegate James , Isenhart Emily , Desouki Mohamed M. , Mastri Michalis , Humphrey Kristen , Dougherty Emily M. , Rosario Spencer R. , Nastiuk Kent L. , Ohm Joyce E. , Eng Kevin H.
Published: September 2022

Like BRCA2, MAGEC3 is an ovarian cancer predisposition gene that has been shown to have prognostic significance in ovarian cancer patients. Despite the clinical significance of each gene, no studies have been conducted to assess the clinical significance of their combined expression. We therefore sought to determine the relationship between MAGEC3 and BRCA2 expression in ovarian cancer and their association with patient characteristics and outcomes. Immunohistochemical staining was quantitated on tumor microarrays of human tumor samples obtained from 357 patients with epithelial ovarian cancer to ascertain BRCA2 expression levels. In conjunction with our previously published MAGEC3 expression data, we observed a weak inverse correlation of MAGEC3 with BRCA2 expression (r = −0.15; p < 0.05) in cases with full-length BRCA2. Patients with optimal cytoreduction, loss of MAGEC3, and detectable BRCA2 expression had better overall (median OS: 127.9 vs. 65.3 months, p = 0.035) and progression-free (median PFS: 85.3 vs. 18.8 months, p = 0.002) survival compared to patients that were BRCA2 expressors with MAGEC3 normal levels. Our results suggest that combined expression of MAGEC3 and BRCA2 serves as a better predictor of prognosis than each marker alone.
Clinical Application of the New Prostate Imaging for Recurrence Reporting (PI-RR) Score Proposed to Evaluate the Local Recurrence of Prostate Cancer after Radical Prostatectomy
Authors: Ciccarese Federica , Corcioni Beniamino , Bianchi Lorenzo , De Cinque Antonio , Paccapelo Alexandro , Galletta Giovanni Luca , Schiavina Riccardo , Brunocilla Eugenio , Golfieri Rita , Gaudiano Caterina
Published: September 2022

Background: We investigated the diagnostic accuracy of the new Prostate Imaging for Recurrence Reporting (PI-RR) score and its inter-observer variability. Secondly, we compared the detection rate of PI-RR and PET and analyzed the correlation between Prostate Specific Antigen (PSA) levels and the PI-RR score. Methods: We included in the analysis 134 patients submitted to multiparametric magnetic resonance imaging for suspected local recurrence. The images were independently reviewed by two radiologists, assigning a value from 1 to 5 to the PI-RR score. Inter-observer agreement and diagnostic accuracy of the PI-RR score (compared to histopathological data, available for 19 patients) were calculated. The detection rate was compared to those of choline PET/CT (46 patients) and PSMA PET/CT (22 patients). The distribution of the PSA values in relation to the PI-RR scores was also analyzed. Results: The accuracy of the PI-RR score was 68.4%. The reporting agreement was excellent (K = 0.884, p < 0.001). The PI-RR showed a higher detection rate than choline PET/CT (69.6% versus 19.6%) and PSMA PET-CT (59.1% versus 22.7%). The analysis of the PSA distribution documented an increase in the PI-RR score as the PSA value increased. Conclusion: The excellent reproducibility of the PI-RR score supports its wide use in the clinical practice to standardize recurrence reporting. The detection rate of PI-RR was superior to that of PET, but was linked to the PSA level.
Comprehensive Molecular Analysis Identified an SRSF Family-Based Score for Prognosis and Therapy Efficiency Prediction in Hepatocellular Carcinoma
Authors: Yuan Jingsheng , Liu Zijian , Wu Zhenru , Yang Jiayin , Lv Tao
Published: September 2022

The serine/arginine-rich splicing factors (SRSF)-mediated alternative splicing plays an essential role in the occurrence and progression of hepatocellular carcinoma (HCC). However, the SRSF-based signature that can predict the prognosis and therapy efficiency is yet to be investigated in HCC. Here, we comprehensively assessed the landscape and prognostic significance of the SRSF family genes in HCC. Then, we screened the SRSF family-related genes for signature construction and explored their biological characteristics. We further established an SRSF score consisting of 18 SRSF-associated genes and evaluated its correlation with prognosis and drug sensitivity in HCC. The predictive power of the SRSF score was validated in independent HCC cohorts and different HCC subgroups. Moreover, we further investigated that knockdown of SRSF11, a pivotal gene in the SRSF score, inhibited CDK1-dependent proliferation and enhanced the drug sensitivity of HCC cells. Overall, our study identified a novel SRSF family-based predictive model, and we demonstrated that SRSF11 is a promising therapeutic target for HCC, which enhances our understanding of the SRSF family genes and provides valuable insights into the clinical treatment and molecular mechanisms of HCC.
A Review and In Silico Analysis of Tissue and Exosomal Circular RNAs: Opportunities and Challenges in Thyroid Cancer
Authors: Toraih Eman A. , Hussein Mohammad H. , Fawzy Manal S. , Kandil Emad
Published: September 2022

Thyroid cancer (TC) is the most common endocrine tumor. The genetic and epigenetic molecular alterations of TC have become more evident in recent years. However, a deeper understanding of the roles these molecular changes play in TC tumorigenesis and progression is essential in developing a successful treatment strategy and improving patients’ prognoses. Circular RNAs (circRNAs), a family of non-coding RNAs, have been implicated in several aspects of carcinogenesis in multiple cancers, including TC. In the current review, we aimed to explore the clinical potential of circRNAs as putative diagnostic, prognostic, and therapeutic targets in TC. The current analyses, including genome-wide circRNA screening and functional enrichment for all deregulated circRNA expression signatures, show that circRNAs display atypical contributions, such as sponging for microRNAs, regulating transcription and translation processes, and decoying for proteins. Given their exceptional clinical advantages, such as higher stability, wider abundance, and occurrence in several body fluids, circRNAs are promising prognostic and theranostic biomarkers for TC.
Survival Benefit of Adjuvant Chemotherapy in Pulmonary Carcinoid Tumors
Authors: Sobash Philip T. , Ullah Asad , Karim Nagla Abdel
Published: September 2022

Pulmonary carcinoid tumors are a rare subtype of neuroendocrine cell tumor found in approximately 1–2% of lung cancers. Management is primarily through surgical resection, with limited benefit of adjuvant therapy in the clinical setting. Genomic profiling is in the nascent stages to molecularly classify these tumors, but there are promising insights for future targeted therapy. A total of 80 abstracts were analyzed for further review with 11 included in our final analysis. Only 4 of the 11 reviewed in depth provided statistical analysis. We evaluated PFS, OS, 1- and 5-year survival as mentioned in the studies. Nodal and KI67 status were also analyzed. Based on the current literature, there is no definitive evidence that adjuvant chemotherapy after resection confers a survival benefit in typical or atypical carcinoids.
Oncogenic Role of ADAM32 in Hepatoblastoma: A Potential Molecular Target for Therapy
Authors: Fukazawa Takahiro , Tanimoto Keiji , Yamaoka Emi , Kojima Masato , Kanawa Masami , Hirohashi Nobuyuki , Hiyama Eiso
Published: September 2022

Outcomes of pediatric hepatoblastoma (HBL) have improved, but refractory cases still occur. More effective and safer drugs are needed that are based on molecular mechanisms. A disintegrin and metalloproteases (ADAMs) are expressed with high frequency in various human carcinomas and play an important role in cancer progression. In this study, we analyzed expression of ADAMs in HBL with a cDNA microarray dataset and found that the expression level of ADAM32 is particularly high. To investigate the role of ADAM32 in cancer, forced expression or knockdown experiments were conducted with HepG2 and HBL primary cells. Colony formation, cell migration and invasion, and cell viability were increased in HepG2 expressing ADAM32, whereas knockdown of ADAM32 induced a decrease in these cellular functions. Quantitative RT-PCR demonstrated an association between ADAM32 expression and the expression of genes related to cancer stem cells and epithelial–mesenchymal transition (EMT), suggesting a role of ADAM32 in cancer stemness and EMT. Furthermore, knockdown of ADAM32 increased cisplatin-induced apoptosis, and this effect was attenuated by a caspase-8 inhibitor, suggesting that ADAM32 plays a role in extrinsic apoptosis signaling. We conclude that ADAM32 plays a crucial role in progression of HBL, so it might be a promising molecular target in anticancer therapy.
p21-Activated Kinase: Role in Gastrointestinal Cancer and Beyond
Authors: Li Xiaodong , Li Feng
Published: September 2022

Gastrointestinal tumors are the most common tumors, and they are leading cause of cancer deaths worldwide, but their mechanisms are still unclear, which need to be clarified to discover therapeutic targets. p21-activating kinase (PAK), a serine/threonine kinase that is downstream of Rho GTPase, plays an important role in cellular signaling networks. According to the structural characteristics and activation mechanisms of them, PAKs are divided into two groups, both of which are involved in the biological processes that are critical to cells, including proliferation, migration, survival, transformation and metabolism. The biological functions of PAKs depend on a large number of interacting proteins and the signaling pathways they participate in. The role of PAKs in tumors is manifested in their abnormality and the consequential changes in the signaling pathways. Once they are overexpressed or overactivated, PAKs lead to tumorigenesis or a malignant phenotype, especially in tumor invasion and metastasis. Recently, the involvement of PAKs in cellular plasticity, stemness and the tumor microenvironment have attracted attention. Here, we summarize the biological characteristics and key signaling pathways of PAKs, and further analyze their mechanisms in gastrointestinal tumors and others, which will reveal new therapeutic targets and a theoretical basis for the clinical treatment of gastrointestinal cancer.
LncRNA SNHG1 Facilitates Tumor Proliferation and Represses Apoptosis by Regulating PPARγ Ubiquitination in Bladder Cancer
Authors: Cai Hongzhou , Xu Haifei , Lu Hongcheng , Xu Weizhang , Liu Haofeng , Wang Xinwei , Zhou Guoren , Yang Xuejian
Published: September 2022

Background: Long noncoding RNAs regulate various biological effects in the progression of cancers. We found that the expression of SNHG1 was significantly up-regulated in bladder cancer after analyzing data obtained from TCGA and GEO. However, the potential role of SNHG1 remains to be investigated in bladder cancer. It was validated that SNHG1 was overexpressed in bladder cancer tissues detected by qRT-PCR and FISH, which was also associated with poor clinical outcome. Additionally, SNHG1 was verified to facilitate tumor proliferation and repress apoptosis in vitro and in vivo. Results: SNHG1 could act as a competitive endogenous RNA and decrease the expression of murine double minute 2 (MDM2) by sponging microRNA-9-3p. Furthermore, MDM2 induced ubiquitination and degradation of PPARγ that contributed to the development of bladder cancer. Conclusions: the study elucidated that SNHG1 played an important role in bladder cancer and provided a potential therapeutic target for bladder cancer.
Advances in Exosomes as Diagnostic and Therapeutic Biomarkers for Gynaecological Malignancies
Authors: Miao Mengdan , Miao Yifei , Zhu Yanping , Wang Junnan , Zhou Huaijun
Published: September 2022

Background: Exosomes are extracellular vesicles that can be released by practically all types of cells. They have a diameter of 30–150 nm. Exosomes control the exchange of materials and information between cells. This function is based on its special cargo-carrying and transporting functions, which can load a variety of useful components and guarantee their preservation. Recently, exosomes have been confirmed to play a significant role in the pathogenesis, diagnosis, treatment, and prognosis of gynaecological malignancies. Particularly, participation in liquid biopsy was studied extensively in gynaecological cancer, which holds the advantages of noninvasiveness and individualization. Literature Review: This article reviews the latest research progress of exosomes in gynaecological malignancies and discusses the involvement of humoral and cell-derived exosomes in the pathogenesis, progression, metastasis, drug resistance and treatment of ovarian cancer, cervical cancer, and endometrial cancer. Advances in the clinical application of exosomes in diagnostic technology, drug delivery, and overcoming tumour resistance are also presented. Conclusion: Exosomes are potentially diagnostic and prognostic biomarkers in gynaecological malignancies, and also provide new directions for the treatment of gynaecological tumours, showing great clinical potential.
Oral Candida spp. Colonisation Is a Risk Factor for Severe Oral Mucositis in Patients Undergoing Radiotherapy for Head & Neck Cancer: Results from a Multidisciplinary Mono-Institutional Prospective Observational Study
Authors: Rupe Cosimo , Gioco Gioele , Almadori Giovanni , Galli Jacopo , Micciché Francesco , Olivieri Michela , Cordaro Massimo , Lajolo Carlo
Published: September 2022

Background: This study aims to find a correlation between Candida spp. oral colonisation prior to radiotherapy (RT) and (i) the development of severe oral mucositis (OM) (grade 3/4) and (ii) early development of severe OM (EOM). Methods: The protocol was registered on ClinicalTrials.gov (ID: NCT04009161) and approved by the ethical committee of the ‘Fondazione Policlinico Universitario Gemelli IRCCS’ (22858/18). An oral swab was obtained before RT to assess the presence of Candida spp. Severe OM occurring before a dose of 40 Gy was defined as EOM. Results: No patient developed G4 OM, and only 36/152 patients (23.7%) developed G3 OM. Tumour site and lymphocytopenia were risk factors for severe OM (OR for tumour site: 1.29, 95% CI: 1–1.67, p = 0.05; OR for lymphocytopenia: 8.2, 95% CI: 1.2–55.8, p = 0.03). We found a correlation between Candida spp. and EOM (OR: 5.13; 95% CI: 1.23–21.4 p = 0.04). Patients with oral colonisation of Candida spp. developed severe OM at a mean dose of 38.3 Gy (range: 28–58; SD: 7.6), while negative patients did so at a mean dose of 45.6 Gy (range: 30–66; SD: 11.1). Conclusions: Candida spp. in the oral cavity appears to be a predictive factor of EOM.
Detecting CdSe Nanomaterials with a Fluorescent Schiff Base Ligand
Authors: Sanmartín-Matalobos Jesús , Bermejo-Barrera Pilar , Pérez-Juste Ignacio , Fondo Matilde , García-Deibe Ana M. , Alves-Iglesias Yeneva
Published: September 2022

We investigated the easily synthesized ligand H3L as a fluorescent chemosensor for the detection of CdSe nanoparticles (CdSe NPs) and L-cysteine-capped CdSe quantum dots (CdSe-Cys QDs) in ethanol–water samples. A drastic quenching of the fluorescence emission of H3L at 510 nm occurred, as a result of the addition of CdSe NPs and CdSe-Cys QDs. A solution of H3L (1.26 ppb) showed sensitive responses to both CdSe NPs and CdSe-Cys QDs, with limits of detection (LOD) as low as 40 and 62 ppb, respectively. Moreover, using a smartphone color recognizer application, the fluorescence intensity response of H3L-modified cellulose paper to CdSe-Cys QDs was recorded on a red channel (R), which allowed us to detect CdSe-Cys QDs with LOD = 15 ppb. Interference of some common metal nanomaterials (NMs), as well as metal ions, in the determination of CdSe NMs in solution was studied. The affinity of H3L to CdSe NPs and CdSe-Cys QDs was spectroscopically determined. Scanning electron microscopy/energy-dispersive X-ray spectroscopy (SEM/EDX), micro-X-ray fluorescence (µ-XRF), 1H-NMR, attenuated total reflection infrared spectroscopy (ATR-IR), and density functional theory (DFT) were also used to investigate the interaction of H3L with CdSe NMs.
Quantitative Analysis of SARS-CoV-2 Antibody Levels in Cancer Patients Post Three Doses of Immunization and Prior to Breakthrough COVID-19 Infections
Authors: Macrae Kathryn , Martinez-Cajas Jorge , Bessai Kristin , Abdulhamed Abulhameed , Gong Yanping
Published: September 2022

(1) Background: COVID-19 vaccine effectiveness should be carefully evaluated and explicitly defined. To our knowledge, this is the first report to quantitatively evaluate humoral responses post 3 doses of SARS-CoV-2 immunization and prior to breakthrough COVID-19 infection in Canadian cancer patients. (2) Methods: In a prospective cohort study, we enrolled 185 cancer participants post COVID-19 vaccination in Kingston, Ontario, Canada. IgG antibodies against the SARS-CoV-2 spike receptor–binding domain were quantified by immunoassay post three doses of immunization. With the COVID-19 rapid antigen test and polymerase chain reaction (PCR), 16 breakthrough infections were identified. Results: Following SARS-CoV-2 vaccination (including BNT162b2, AZD1222, and mRNA-1273), the mean serum anti-spike protein antibody level was 197.2 BAU/mL (binding antibody unit, SD ± 393.9), 1335.9 BAU/mL (±3337.8), and 3164.8 BAU/mL (±6500.9) post the first, second, and third dose of vaccination. Observed differences were significant (p ≤ 0.001). The average antibody level of 3164.8 BAU/mL post the third dose was 89.9 times that of the seroconversion level (35.2 BAU/mL). This indicates that most vaccines approved are effective in producing robust antibody responses. In 11 breakthrough cases confirmed by PCR, prior to infection, the average antibody concentration was 3675.6 BAU/mL with the highest concentration being 9107.4 BAU/mL. Compared with this average antibody concentration of 3675.6 BAU/mL (104.4 times that of the seroconversion concentration), 0% of single dosed, 9.6% of double vaccinated, and 29.5% of triple vaccinated cancer patients had higher SARS-CoV-2 antibody levels. When patients were split into hematological and solid cancer, the hematological cancer group demonstrated lower serological responses than the solid cancer group in the first and second doses (first dose, average concentration 11.1 vs. 201.4 BAU/mL, respectively, p < 0.05; second dose, average concentration 441.5 vs. 1725.9 BAU/mL, respectively, p < 0.05). There was no difference in the third dose level (1756.3 vs. 2548.0 BAU/mL, p = 0.21). (4) Conclusions: Most vaccines were effective in producing robust antibody responses when more than one dose was given, and the more doses the higher the serological response. Likely due to the highly contagious nature of SARS-CoV-2 variants, a significant number of participants had SARS-CoV-2 antibody responses lower than the average antibody concentration prior to the known breakthrough infections. Additional vaccination is likely required to ensure immunity against infection by SARS-CoV-2.
Emerging Systemic Therapies in Advanced Unresectable Biliary Tract Cancer: Review and Canadian Perspective
Authors: Tam Vincent C. , Ramjeesingh Ravi , Burkes Ronald , Yoshida Eric M. , Doucette Sarah , Lim Howard J.
Published: September 2022

Biliary tract cancer (BTC) is a group of rare and aggressive malignancies with a dismal prognosis. There is currently a significant lack in effective treatment options for BTC, with gemcitabine-cisplatin remaining the first-line standard of care treatment for over a decade. A wave of investigational therapies, including new chemotherapy combinations, immunotherapy, and biomarker-driven targeted therapy have demonstrated promising results in BTC, and there is hope for many of these therapies to be incorporated into the Canadian treatment landscape in the near future. This review discusses the emerging therapies under investigation for BTC and provides a perspective on how they may fit into Canadian practice, with a focus on the barriers to treatment access.
Gastrointestinal Stromal Tumors: 10-Year Experience in Cancer Center—The Ottawa Hospital (TOH)
Authors: Alfagih Abdulhameed , AlJassim Abdulaziz , Alshamsan Bader , Alqahtani Nasser , Asmis Timothy
Published: September 2022

(1) Background: The management of gastrointestinal stromal tumors (GIST) has significantly evolved over the last two decades, with the introduction of tyrosine kinase inhibitors (TKI). We aim to report 10 years of experience of GIST management at a regional cancer center in Canada. (2) Methods: We retrospectively analyzed the records of 248 consecutive patients diagnosed with GIST between 2011 and 2021. We describe the clinical and pathological data, management, and outcome, including survival. (3) Results: The most common GIST sites were the stomach 63% (156), followed by the small bowel 29% (73). At diagnosis, 83% (206) of patients had localized disease (stage I–III). According to the modified National Institutes of Health consensus criteria (NIH) for GIST, around 45% (90) had intermediate or high-risk disease. Most patients, 86% (213), underwent curative surgical resection. Forty-nine patients received adjuvant imatinib, while forty-three patients had advanced disease and received at least one line of TKI. With a median follow-up of 47 months, the 5-year recurrence-free survival (RFS) rates for very low and low risk were 100% and 94%, respectively, while those for intermediate and high risk were 84% and 51%, respectively. The 5-year overall survival (OS) rates for very low and low risk were 100% and 94%, while intermediate, high risk, and advanced were 91%, 88%, and 65%, respectively. Using the Kaplan–Meier method, there were statistically significant differences in RFS and OS between NIH risk groups, p < 0.0005. In univariate analysis, ECOG, site, mitosis, secondary malignancy, and size were predictors for OS. High mitosis and large size (>5 cm) were associated with worse RFS. (4) Conclusions: Curative surgical resection remains the gold standard management of GIST. Our results are comparable to the reported literature. Further research is needed to explore histology’s role in risk stratification and initiating adjuvant TKI.