bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural Application of Eco-Friendly Composites from Recycled Wood Fibres Bonded with Magnesium Lignosulfonate
Authors: Antov Petar , Jivkov Vassil , Savov Viktor , Simeonova Ralitsa , Yavorov Nikolay
Published: October 2020

The pulp and paper industry generates substantial amounts of solid waste and wastewater, which contain waste fibres. The potential of using these recycled wood fibres for producing eco-friendly composites that were bonded with a formaldehyde-free adhesive (magnesium lignosulfonate) and their use in structural applications was evaluated in this study. Fibreboards were produced in the laboratory with a density of 720 kg·m−3 and 15% magnesium lignosulfonate gluing content, based on the dry fibres. The mechanical properties (bending strength, modulus of elasticity and internal bond strength), physical properties (thickness swelling and water absorption) and formaldehyde content were determined and compared with the European Standards requirements for wood-based panels. In general, the laboratory-produced panels demonstrated acceptable mechanical properties, such as bending strength (18.5 N·mm−2) and modulus of elasticity (2225 N·mm−2), which were higher than the minimum requirements for type P2 particleboards and equal to the requirements for MDF panels. The moisture properties, i.e., thickness swelling (24 h) and water absorption (24 h) significantly deteriorated. The free formaldehyde content of the laboratory-produced composites (1.1 mg/100 g) reached the super E0 grade (≤1.5 mg/100 g), which allowed for their classification as eco-friendly, low-emission wood-based composites. The L-type corner joints, made from the developed composites, demonstrated significantly lower bending capacity (from 2.5 to 6.5 times) compared to the same joints made from MDF panels. Nevertheless, the new eco-friendly composites can be efficiently utilised as a structural material in non-load-bearing applications.
Accessibility Evaluation of Saudi E-Government Systems for Teachers: A Visually Impaired User’s Perspective
Authors: AlSaeed Duaa , Alkhalifa Hend , Alotaibi Hind , Alshalan Raghad , Al-Mutlaq Nourah , Alshalan Shahad , Bintaleb Hind Taleb , AlSahow Areej Mansour
Published: October 2020

The Saudi government pays great attention to the usability and accessibility issues of e-government systems. E-government educational systems, such as Noor, Faris, and iEN systems, are some of the most rapidly developing e-government systems. In this study, we used a mixed-methods approach (usability testing and automated tools evaluation) to investigate the degree of difficulty faced by teachers with visual impairment while accessing such systems. The usability testing was done on four visually impaired teachers. In addition, four automated tools, namely, AChecker, HTML_CodeSniffer, SortSite, and Total Validator, were utilized in this study. The results showed that all three systems failed to support screen readers effectively as it was the main issue reported by the participants. On the other hand, the automated evaluation tools helped with identifying the most prominent accessibility issues of these systems. The perceivable principle was the principle most violated by the three systems, followed by operable, and then robust. The errors corresponding to the perceivable principle alone represented around 73% of the total errors. Moreover, further analysis revealed that most of the detected errors violated even the lowest level of accessibility conformance, which reflected the failure of these systems to pass the accessibility evaluation.
The Antioxidant, Anti-Apoptotic, and Proliferative Potency of Argan Oil against Betamethasone-Induced Oxidative Renal Damage in Rats
Authors: Orabi Sahar Hassan , Allam Tamer S. , Shawky Sherif Mohamed , Tahoun Enas Abd El-aziz , Khalifa Hanem K. , Almeer Rafa , Abdel-Daim Mohamed M. , El-Borai Nermeen Borai , Mousa Ahmed Abdelmoniem
Published: October 2020

The present study aimed to investigate the protective effect of argan oil (AO) against nephrotoxic effects following overdose and long-term administration of betamethasone (BM). The phytochemical compositions of AO were assessed using GC/MS. Forty eight male Wister albino rats were divided into six groups and treated for 3 successive weeks. The control group was orally administrated distilled water daily, the BM group received BM (1 mg/kg, IM, day after day), AO/0.5 and AO/1 groups received AO (0.5 mL/kg, 1 mL/kg, orally, daily, respectively), BM + AO/0.5 group and BM + AO/1 group. The results revealed that BM induced hematological changes, including reduction of red blood cells with leukocytosis, neutrophilia, monocytosis, lymphocytopenia, and thrombocytopenia. Moreover, BM caused a significant increase of serum urea and creatinine levels, and renal malondialdehyde and nitric oxide contents with significant decrease of reduced glutathione content. BM also caused vascular, degenerative, and inflammatory histopathological alterations in kidney, along with an increase in the Bax/Bcl-2 ratio, activation of caspase-3, and decrease of proliferating cell nuclear antigen expression. Conversely, the concomitant administration of AO (0.5, 1 mL/kg) with BM ameliorated the aforementioned hematological, biochemical, pathological, and histochemical BM adverse effects. In conclusion, AO has protective effects against BM-induced renal damage, possibly via its antioxidant, anti-apoptotic, and proliferative properties.
Allograft Inflammatory Factor-1 in Metazoans: Focus on Invertebrates
Authors: Vizioli Jacopo , Verri Tiziano , Pagliara Patrizia
Published: October 2020

Allograft inflammatory factor-1 (AIF-1) is a calcium-binding scaffold/adaptor protein often associated with inflammatory diseases. Originally cloned from active macrophages in humans and rats, this gene has also been identified in other vertebrates and in several invertebrate species. Among metazoans, AIF-1 protein sequences remain relatively highly conserved. Generally, the highest expression levels of AIF-1 are observed in immunocytes, suggesting that it plays a key role in immunity. In mammals, the expression of AIF-1 has been reported in different cell types such as activated macrophages, microglial cells, and dendritic cells. Its main immunomodulatory role during the inflammatory response has been highlighted. Among invertebrates, AIF-1 is involved in innate immunity, being in many cases upregulated in response to biotic and physical challenges. AIF-1 transcripts result ubiquitously expressed in all examined tissues from invertebrates, suggesting its participation in a variety of biological processes, but its role remains largely unknown. This review aims to present current knowledge on the role and modulation of AIF-1 and to highlight its function along the evolutionary scale.
Effectivity of Two Cell Proliferation Markers in Brain of a Songbird Zebra Finch
Authors: Kubikova Lubica , Polomova Justina , Mikulaskova Viktoria , Lukacova Kristina
Published: October 2020

There are two most heavily used markers of cell proliferation, thymidine analogues 5-bromo-2′-deoxyuridine (BrdU) and 5-ethynyl-2′-deoxyuridine (EdU) that are incorporated into the DNA during its synthesis. In neurosciences, they are often used consecutively in the same animal to detect neuronal populations arising at multiple time points, their migration and incorporation. The effectivity of these markers, however, is not well established. Here, we studied the effectivity of equimolar doses of BrdU and EdU to label new cells and looked for the dose that will label the highest number of proliferating cells in the neurogenic ventricular zone (VZ) of adult songbirds. We found that, in male zebra finches (Taeniopygia guttata), the equimolar doses of BrdU and EdU did not label the same number of cells, with BrdU being more effective than EdU. Similarly, in liver, BrdU was more effective. The saturation of the detected brain cells occurred at 50 mg/kg BrdU and above 41 mg/kg EdU. Higher dose of 225 mg/kg BrdU or the equimolar dose of EdU did not result in any further significant increases. These results show that both markers are reliable for the detection of proliferating cells in birds, but the numbers obtained with BrdU and EdU should not be compared.
Metformin Ameliorates Lipopolysaccharide-Induced Depressive-Like Behaviors and Abnormal Glutamatergic Transmission
Authors: Chen Jiang , Zhou Tian , Guo A-Min , Chen Wen-Bing , Lin Dong , Liu Zi-Yang , Fei Er-Kang
Published: October 2020

Metformin, a first-line drug for type 2 diabetes mellitus (T2DM), has been found to reduce depressive symptoms in patients with comorbid depression and other diseases. However, it is largely unclear how metformin ameliorates depressive-like behaviors. Here, we used lipopolysaccharide (LPS) to induce depressive-like behaviors in mice and found that LPS-treated mice exhibited increased immobility in the forced swimming test (FST) and tail suspension test (TST), as well as increased glutamatergic transmission. Furthermore, metformin administration in the LPS-treated mice ameliorated depressive-like behaviors and elevated glutamatergic transmission. Our results suggest that metformin has antidepressant effects and can correct abnormal glutamatergic transmission, providing an insight into the underlying mechanism by which metformin acts against depression.
Silkworm Pupae Function as Efficient Producers of Recombinant Glycoproteins with Stable-Isotope Labeling
Authors: Yagi Hirokazu , Yanaka Saeko , Yogo Rina , Ikeda Akari , Onitsuka Masayoshi , Yamazaki Toshio , Kato Tatsuya , Park Enoch Y. , Yokoyama Jun , Kato Koichi
Published: October 2020

Baculovirus-infected silkworms are promising bioreactors for producing recombinant glycoproteins, including antibodies. Previously, we developed a method for isotope labeling of glycoproteins for nuclear magnetic resonance (NMR) studies using silkworm larvae reared on an artificial diet containing 15N-labeled yeast crude protein extract. Here, we further develop this method by introducing a technique for the expression of isotope-labeled glycoproteins by silkworm pupae, which has several potential advantages relative to larvae-based techniques in terms of production yield, ease of handling, and storage. Here, we fed fifth instar larvae an artificial diet with an optimized composition containing [methyl-13C]methionine, leading to pupation. Nine-day-old pupae were then injected with recombinant Bombyx mori nucleopolyhedrovirus (BmNPV) bacmid for expression of recombinant human immunoglobulin G (IgG). From the whole-body homogenates of pupae, 0.35 mg/pupa of IgG was harvested, which is a yield that is five times higher than can be obtained from larvae. Recombinant IgG, thus prepared, exhibited mainly three kinds of pauci-mannose-type oligosaccharides and had a 13C-enrichment ratio of approximately 80%. This enabled selective observation of NMR signals originating from the methionyl methyl group of IgG, confirming its conformational integrity. These data demonstrate the utility of silkworm pupae as factories for producing recombinant glycoproteins with amino-acid-selective isotope labeling.
Neutrophil-to-Lymphocyte Ratio and Symptomatic Hemorrhagic Transformation in Ischemic Stroke Patients Undergoing Revascularization
Authors: Świtońska Milena , Piekuś-Słomka Natalia , Słomka Artur , Sokal Paweł , Żekanowska Ewa , Lattanzi Simona
Published: October 2020

Objectives: Symptomatic hemorrhagic transformation (sHT) is a life-threatening complication of acute ischemic stroke (AIS). The early identification of the patients at increased risk of sHT can have clinically relevant implications. The aim of this study was to explore the validity and accuracy of the neutrophil-to-lymphocyte ratio (NLR) in predicting sHT in patients with AIS undergoing revascularization. Methods: Consecutive patients hospitalized for AIS who underwent intravenous thrombolysis, mechanical thrombectomy or both were identified. The NLR values were estimated at admission. The study endpoint was the occurrence of sHT within 24 h from stroke treatment. Results: Fifty-one patients with AIS were included, with a median age of 67 (interquartile range, 55–78) years. sHT occurred in 10 (19.6%) patients. Patients who developed sHT had higher NLR at admission. NLR was an independent predictor of sHT and showed good discriminatory power (area under the curve 0.81). In a multivariable analysis, NLR and systolic blood pressure were independently associated with sHT. Conclusions: NLR at admission can accurately predict sHT in patients with AIS undergoing revascularization.
Quantitative Identification of Functional Connectivity Disturbances in Neuropsychiatric Lupus Based on Resting-State fMRI: A Robust Machine Learning Approach
Authors: Simos Nicholas John , Dimitriadis Stavros I. , Kavroulakis Eleftherios , Manikis Georgios C. , Bertsias George , Simos Panagiotis , Maris Thomas G. , Papadaki Efrosini
Published: October 2020

Neuropsychiatric systemic lupus erythematosus (NPSLE) is an autoimmune entity comprised of heterogenous syndromes affecting both the peripheral and central nervous system. Research on the pathophysiological substrate of NPSLE manifestations, including functional neuroimaging studies, is extremely limited. The present study examined person-specific patterns of whole-brain functional connectivity in NPSLE patients (n = 44) and age-matched healthy control participants (n = 39). Static functional connectivity graphs were calculated comprised of connection strengths between 90 brain regions. These connections were subsequently filtered through rigorous surrogate analysis, a technique borrowed from physics, novel to neuroimaging. Next, global as well as nodal network metrics were estimated for each individual functional brain network and were input to a robust machine learning algorithm consisting of a random forest feature selection and nested cross-validation strategy. The proposed pipeline is data-driven in its entirety, and several tests were performed in order to ensure model robustness. The best-fitting model utilizing nodal graph metrics for 11 brain regions was associated with 73.5% accuracy (74.5% sensitivity and 73% specificity) in discriminating NPSLE from healthy individuals with adequate statistical power. Closer inspection of graph metric values suggested an increased role within the functional brain network in NSPLE (indicated by higher nodal degree, local efficiency, betweenness centrality, or eigenvalue efficiency) as compared to healthy controls for seven brain regions and a reduced role for four areas. These findings corroborate earlier work regarding hemodynamic disturbances in these brain regions in NPSLE. The validity of the results is further supported by significant associations of certain selected graph metrics with accumulated organ damage incurred by lupus, with visuomotor performance and mental flexibility scores obtained independently from NPSLE patients.
Neuronal Localization of SENP Proteins with Super Resolution Microscopy
Authors: Colnaghi Luca , Conz Andrea , Russo Luca , Musi Clara A. , Fioriti Luana , Borsello Tiziana , Salmona Mario
Published: October 2020

SUMOylation of proteins plays a key role in modulating neuronal function. For this reason, the balance between protein SUMOylation and deSUMOylation requires fine regulation to guarantee the homeostasis of neural tissue. While extensive research has been carried out on the localization and function of small ubiquitin-related modifier (SUMO) variants in neurons, less attention has been paid to the SUMO-specific isopeptidases that constitute the human SUMO-specific isopeptidase (SENP)/Ubiquitin-Specific Protease (ULP) cysteine protease family (SENP1-3 and SENP5-7). Here, for the first time, we studied the localization of SENP1, SENP6, and SENP7 in cultured hippocampal primary neurons at a super resolution detail level, with structured illumination microscopy (SIM). We found that the deSUMOylases partially colocalize with pre- and post-synaptic markers such as synaptophysin and drebrin. Thus, further confirming the presence with synaptic markers of the negative regulators of the SUMOylation machinery.
Diagnosis and Treatment of Drug-Resistant Epilepsy: Present and Future Perspectives
Authors: Assenza Giovanni
Published: October 2020

The introduction of the operative definition of drug-resistant epilepsy (DRE) was a turning point for clinicians and people with epilepsy (PwE) [...]
Lightweight Building of an Electroencephalogram-Based Emotion Detection System
Authors: Al-Nafjan Abeer , Alharthi Khulud , Kurdi Heba
Published: October 2020

Brain–computer interface (BCI) technology provides a direct interface between the brain and an external device. BCIs have facilitated the monitoring of conscious brain electrical activity via electroencephalogram (EEG) signals and the detection of human emotion. Recently, great progress has been made in the development of novel paradigms for EEG-based emotion detection. These studies have also attempted to apply BCI research findings in varied contexts. Interestingly, advances in BCI technologies have increased the interest of scientists because such technologies’ practical applications in human–machine relationships seem promising. This emphasizes the need for a building process for an EEG-based emotion detection system that is lightweight, in terms of a smaller EEG dataset size and no involvement of feature extraction methods. In this study, we investigated the feasibility of using a spiking neural network to build an emotion detection system from a smaller version of the DEAP dataset with no involvement of feature extraction methods while maintaining decent accuracy. The results showed that by using a NeuCube-based spiking neural network, we could detect the valence emotion level using only 60 EEG samples with 84.62% accuracy, which is a comparable accuracy to that of previous studies.
Monitoring of Structural Safety of Buildings Using Wireless Network of MEMS Sensors
Authors: Zabielski Jacek , Srokosz Piotr
Published: October 2020

The 21st century abounds in modern electronic-information technologies, which are applied in many areas of life. Amongst many modern technologies there is also the Internet of Things (IoT) that is the concept of incorporating objects and devices equipped with a communication interface into the telecommunication and IT networks. This particular feature makes IoT a paradigm that can be successfully applied to measurement systems used in research in civil engineering, especially using a wireless sensor network deployed in scattered research locations. In turn, technological progress in the miniaturization of sensors and controllers allows the construction of very efficient and low-cost systems for monitoring the physical parameters of buildings, which are safety indicators. The main purpose of this paper is to present the concept of wireless network of MEMS-based sensors with particular emphasis on its application in monitoring of structural safety including the author’s own system based on Long Range (LoRa) technology. The exact novelty of the proposed concept is the synergistic synthesis of solutions in the field of electronics, micromechanics and computer science, applied for civil engineering purposes. The system consists of MEMS accelerometers based on MPU6050 chips and A1302 Hall-effect sensors supported by AVR microcontrollers and LoRa transceivers based on RF98 chips operating at 433 MHz. The prototype of the measuring network was installed in a selected university building in which structural discontinuities (wall cracks) were noted. Sample results of measurements of the impact of service loads on the building structure behavior were presented in the form of accelerograms.
Hypertensive Disorders of Pregnancy (HDP) and the Risk of Common Cancers in Women: Evidence from the European Prospective Investigation into Cancer (EPIC)-Norfolk Prospective Population-Based Study
Authors: Pasdar Zahra , Gamble David T. , Myint Phyo K. , Luben Robert N. , Wareham Nicholas J. , Khaw Kay-Tee , Bhattacharya Sohinee
Published: October 2020

Purpose: The purpose was to determine the association between HDP and cancer in a UK cohort. Methods: Between 1993 and 1997, participants from the EPIC-Norfolk cohort attended baseline health-checks and completed questionnaires, where a history of HDP was collected. Incident cancer cases were identified through NHS record linkage until March 2016. Univariable and multivariable logistic regression analyses were employed to determine the association between HDP and odds of cancer, with adjustment for potential confounders including co-morbidities, sociodemographic, lifestyle and reproductive factors. Results: 13,562 women were included after excluding prevalent cancer cases and women with no pregnancies. 2919 (21.5%) reported HDP and 2615 incident cancers occurred during mean follow up of 19 years. Median age (IQR) at baseline for incident cancer was 60.8 (±14.8) years. Among incident cancer cases, 578 (22.1%) had HDP. In multivariable analyses, HDP had odds ratio (OR) 1.06; 95% CI 0.95–1.18 for incident cancer. The ORs (95% CIs) for common site-specific cancers including breast, colorectal, lung, ovarian and endometrial cancers were 1.06 (0.88–1.28), 1.15 (0.92–1.45), 0.96 (0.68–1.35), 1.30 (0.93–1.83) and 1.16 (0.80–1.67). Conclusion: We found no association between HDP and cancer risk. Further studies are required to confirm and account for any underlying genetic factors involved in pregnancy-related exposures and cancer risk.
Molecular and Cellular Modelling of Salivary Gland Tumors Open New Landscapes in Diagnosis and Treatment
Authors: Porcheri Cristina , Meisel Christian T. , Mitsiadis Thimios A.
Published: October 2020

Salivary gland tumors are neoplasms affecting the major and minor salivary glands of the oral cavity. Their complex pathological appearance and overlapping morphological features between subtypes, pose major challenges in the identification, classification, and staging of the tumor. Recently developed techniques of three-dimensional culture and organotypic modelling provide useful platforms for the clinical and biological characterization of these malignancies. Additionally, new advances in genetic and molecular screenings allow precise diagnosis and monitoring of tumor progression. Finally, novel therapeutic tools with increased efficiency and accuracy are emerging. In this review, we summarize the most common salivary gland neoplasms and provide an overview of the state-of-the-art tools to model, diagnose, and treat salivary gland tumors.
Randomized Phase II Study with Cetuximab in Combination with 5-FU and Cisplatin or Carboplatin Vs. Cetuximab in Combination with Paclitaxel and Carboplatin for Treatment of Patients with Relapsed or Metastatic Squamous Cell Carcinoma of the Head and Neck (CETMET Trial)
Authors: Tsakonas Georgios , Specht Lena , Kristensen Claus Andrup , Moreno Maria Herlestam Calero , Haugen Cange Hedda , Soderstrom Karin , Friesland Signe
Published: October 2020

Background: Platinum-based chemotherapy with cetuximab is the standard of care for relapsed or metastatic squamous cell carcinoma of the head and neck (SCCHN). The aim of this trial was to investigate whether cetuximab and paclitaxel/carboplatin can achieve similar progression-free survival (PFS) with standard cetuximab and 5-FU/platinum-based chemotherapy. Standard chemotherapy treatment for SCCHN is related to severe toxicity and new, less toxic regimens are needed. Methods: In this multicentre, randomized, controlled, phase 2 trial, 85 patients with relapsed or metastatic SCCHN were randomized in a 1:1 ratio to cetuximab and 5-FU/cisplatin or carboplatin (arm A) vs. cetuximab and paclitaxel/carboplatin (arm B). Eligibility criteria included age ≥18 years, Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0–1, and adequate organ functions. The primary endpoint was to investigate whether PFS in arm B is significantly worse than PFS in arm A. Results: Median PFS in arm A was 4.37 months (95% CI: 2.9–5.9 m) and 6.5 months (95% CI: 4.8–8.2 m) in arm B, (p = 0.064). Median overall survival (OS) was 8.4 months (95% CI: 5.3–11.5 m) in arm A and 10.2 months (95% CI: 5.4–15 m) in arm B, (HR = 0.71; 95% CI: 0.43–1.16). PFS HR for arm B was not significantly worse than arm A (HR = 0.65; 95% CI: 0.41–1.03). Adverse events ≥ grade 3 were more frequent in arm A than arm B (60% vs. 40%; p = 0.034). Conclusion: Cetuximab and paclitaxel/carboplatin was found to have similar efficacy and less toxicity compared to cetuximab and 5-FU/cisplatin or carboplatin. The experimental arm is easier to administer rendering it a favorable alternative to standard therapy.
Implementing ctDNA Analysis in the Clinic: Challenges and Opportunities in Non-Small Cell Lung Cancer
Authors: Gobbini Elisa , Swalduz Aurélie , Giaj Levra Matteo , Ortiz-Cuaran Sandra , Toffart Anne-Claire , Pérol Maurice , Moro-Sibilot Denis , Saintigny Pierre
Published: October 2020

Tumor genomic profiling has a dramatic impact on the selection of targeted treatment and for the identification of resistance mechanisms at the time of progression. Solid tissue biopsies are sometimes challenging, and liquid biopsies are used as a non-invasive alternative when tissue is limiting. The clinical relevance of tumor genotyping through analysis of ctDNA is now widely recognized at all steps of the clinical evaluation process in metastatic non-small cell lung cancer (NSCLC) patients. ctDNA analysis through liquid biopsy has recently gained increasing attention as well in the management of early and locally advanced, not oncogene-addicted, NSCLC. Its potential applications in early disease detection and the response evaluation to radical treatments are promising. The aim of this review is to summarize the landscape of liquid biopsies in clinical practice and also to provide an overview of the potential perspectives of development focusing on early detection and screening, the assessment of minimal residual disease, and its potential role in predicting response to immunotherapy. In addition to available studies demonstrating the clinical relevance of liquid biopsies, there is a need for standardization and well-designed clinical trials to demonstrate its clinical utility.
Genetic Variants of the TERT Gene, Telomere Length, and Circulating TERT as Prognostic Markers in Rectal Cancer Patients
Authors: Rampazzo Enrica , Cecchin Erika , Del Bianco Paola , Menin Chiara , Spolverato Gaya , Giunco Silvia , Lonardi Sara , Malacrida Sandro , De Paoli Antonino , Toffoli Giuseppe , Pucciarelli Salvatore , De Rossi Anita
Published: October 2020

Single-nucleotide polymorphisms (SNPs) in the TERT gene can affect telomere length and TERT expression and have been associated with risk and/or outcome for several tumors, but very few data are available about their impact on rectal cancer. Eight SNPs (rs2736108, rs2735940, rs2736098, rs2736100, rs35241335, rs11742908, rs2736122 and rs2853690), mapping in regulatory and coding regions of the TERT gene, were studied in 194 rectal cancer patients to evaluate their association with constitutive telomere length, circulating TERT mRNA levels, response to neoadjuvant chemoradiotherapy (CRT) and disease outcome. At diagnosis, the rs2736100CC genotype was associated with longer telomeres measured pre-CRT, while the rs2736100CC, rs2736108TT and rs2735940AA were associated with greater telomere erosion evaluated post-CRT. The rs2736108CC and rs2853690AA/GG genotypes, respectively associated with lower telomere erosion and lower levels of circulating TERT post-CRT, were also independently associated with a better response to therapy [OR 4.6(1.1–19.1) and 3.0(1.3–6.9)]. Overall, post-CRT, low levels (≤ median value) of circulating TERT and its stable/decreasing levels compared to those pre-CRT, were independently associated with a better response to therapy [OR 5.8(1.9–17.8) and 5.3(1.4–19.4), respectively]. Furthermore, post-CRT, patients with long telomeres (>median value) and low levels of circulating TERT had a significantly lower risk of disease progression [HR 0.4(0.1–0.9) and 0.3(0.1–0.8), respectively]. These findings suggest that TERT SNPs could be a useful tool for improving the selection of patients who could benefit from CRT and support the role of telomere length and circulating TERT mRNA levels as useful markers for monitoring the response to therapy and disease outcome in rectal cancer patients.
Evaluation of Carbon Ion Radiation-Induced Trismus in Head and Neck Tumors Using Dose-Volume Histograms
Authors: Musha Atsushi , Shimada Hirofumi , Kubo Nobuteru , Kawamura Hidemasa , Okano Naoko , Miyasaka Yuhei , Sato Hiro , Shirai Katsuyuki , Saitoh Jun-ichi , Yokoo Satoshi , Chikamatsu Kazuaki , Ohno Tatsuya
Published: October 2020

Carbon ion radiotherapy (C-ion RT) provides a highly localized deposition of energy that can increase radiation doses to tumors while minimizing irradiation of adjacent normal tissues. For tumors located near the temporomandibular joint, C-ion RT-induced trismus may occur. However, the relationship between the carbon ion dose and the onset of trismus is unclear. In this prospective observational study, we assessed the trismus/carbon ion dose relationship using dose−volume histograms in 35 patients who received C-ion RT in their head and neck regions between 2010 and 2014. Trismus was evaluated in patients according to the Common Terminology Criteria for Adverse Events, version 4.0. All patients were treated with 57.6 or 64.0 Gy (relative biological effectiveness (RBE)) in 16 fractions, and the median follow-up time was 57 months. Grade 2 trismus was observed in six patients. The median onset time was 12 months. At maximum radiation doses, all masticatory muscles and coronoid processes, particularly the masseter muscle, were significantly different (p = 0.003). The contouring of the masseter muscle and coronoid process requires different treatment planning. The maximum radiation doses of the coronoid process can be proposed as a guideline for treatment planning, considering the ease of contouring in C-ion RT.
The Role of Adenovirus in Cancer Therapy
Authors: Sato-Dahlman Mizuho , Roach Brett Lee , Yamamoto Masato
Published: October 2020

This series of 13 articles (7 original articles, 6 reviews) is presented by international leaders in adenovirus-based cancer therapy [...]
Combination of Irreversible Electroporation and STING Agonist for Effective Cancer Immunotherapy
Authors: Go Eun-Jin , Yang Hannah , Chon Hong Jae , Yang DaSom , Ryu WonHyoung , Kim Dong-Hyun , Han Dong Keun , Kim Chan , Park Wooram
Published: October 2020

Recently, cancer immunotherapy has received attention as a viable solution for the treatment of refractory tumors. However, it still has clinical limitations in its treatment efficacy due to inter-patient tumor heterogeneity and immunosuppressive tumor microenvironment (TME). In this study, we demonstrated the triggering of anti-cancer immune responses by a combination of irreversible electroporation (IRE) and a stimulator of interferon genes (STING) agonist. Optimal electrical conditions inducing damage-associated molecular patterns (DAMPs) by immunogenic cell death (ICD) were determined through in vitro 2D and 3D cell experiments. In the in vivo syngeneic lung cancer model, the combination of IRE and STING agonists demonstrated significant tumor growth inhibition. We believe that the combination strategy of IRE and STING agonists has potential for effective cancer immunotherapy.
Temozolomide Treatment Increases Fatty Acid Uptake in Glioblastoma Stem Cells
Authors: Caragher Seamus , Miska Jason , Shireman Jack , Park Cheol H. , Muroski Megan , Lesniak Maciej S. , Ahmed Atique U.
Published: October 2020

Among all cancers, glioblastoma (GBM) remains one of the least treatable. One key factor in this resistance is a subpopulation of tumor cells termed glioma stem cells (GSCs). These cells are highly resistant to current treatment modalities, possess marked self-renewal capacity, and are considered key drivers of tumor recurrence. Further complicating an understanding of GBM, evidence shows that the GSC population is not a pre-ordained and static group of cells but also includes previously differentiated GBM cells that have attained a GSC state secondary to environmental cues. The metabolic behavior of GBM cells undergoing plasticity remains incompletely understood. To that end, we probed the connection between GSCs, environmental cues, and metabolism. Using patient-derived xenograft cells, mouse models, transcriptomics, and metabolic analyses, we found that cell state changes are accompanied by sharp changes in metabolic phenotype. Further, treatment with temozolomide, the current standard of care drug for GBM, altered the metabolism of GBM cells and increased fatty acid uptake both in vitro and in vivo in the plasticity driven GSC population. These results indicate that temozolomide-induced changes in cell state are accompanied by metabolic shifts—a potentially novel target for enhancing the effectiveness of current treatment modalities.
Alarmins and c-Jun N-Terminal Kinase (JNK) Signaling in Neuroinflammation
Authors: Anfinogenova Nina D. , Quinn Mark T. , Schepetkin Igor A. , Atochin Dmitriy N.
Published: October 2020

Neuroinflammation is involved in the progression or secondary injury of multiple brain conditions, including stroke and neurodegenerative diseases. Alarmins, also known as damage-associated molecular patterns, are released in the presence of neuroinflammation and in the acute phase of ischemia. Defensins, cathelicidin, high-mobility group box protein 1, S100 proteins, heat shock proteins, nucleic acids, histones, nucleosomes, and monosodium urate microcrystals are thought to be alarmins. They are released from damaged or dying cells and activate the innate immune system by interacting with pattern recognition receptors. Being principal sterile inflammation triggering agents, alarmins are considered biomarkers and therapeutic targets. They are recognized by host cells and prime the innate immune system toward cell death and distress. In stroke, alarmins act as mediators initiating the inflammatory response after the release from the cellular components of the infarct core and penumbra. Increased c-Jun N-terminal kinase (JNK) phosphorylation may be involved in the mechanism of stress-induced release of alarmins. Putative crosstalk between the alarmin-associated pathways and JNK signaling seems to be inherently interwoven. This review outlines the role of alarmins/JNK-signaling in cerebral neurovascular inflammation and summarizes the complex response of cells to alarmins. Emerging anti-JNK and anti-alarmin drug treatment strategies are discussed.
Influence of GLAD Sputtering Configuration on the Crystal Structure, Morphology, and Gas-Sensing Properties of the WO3 Films
Authors: Zarzycki Arkadiusz , Dyndał Katarzyna , Sitarz Maciej , Xu Jie , Gao Feng , Marszałek Konstanty , Rydosz Artur
Published: October 2020

In this paper, we describe a deposition method and investigation of the physical properties of WO3 films. We investigated tungsten oxide due to its potential application as a gas sensor. Thin films of the WO3 were deposited on glass, silicon, and alumina substrates by magnetron GLAD sputtering. The crystallinity of films was determined by X-ray diffraction (XRD) and the thickness by X-Ray Reflectivity (XRR) and spectroscopic ellipsometry (SE). Surface morphology, which is important for gas sensitivity, was measured by atomic force microscopy (AFM). We studied the gas-sensing characteristics under exposure to acetone in the 0.1–1.25 ppm range which covers the levels of exhaled breath acetone. We show that WO3 sensors have different sensitivity for different sputter angle. Furthermore, we demonstrate the influence of temperature during gas content measurement.
Statistical Approach for Biologically Relevant Gene Selection from High-Throughput Gene Expression Data
Authors: Das Samarendra , Rai Shesh N.
Published: October 2020

Selection of biologically relevant genes from high-dimensional expression data is a key research problem in gene expression genomics. Most of the available gene selection methods are either based on relevancy or redundancy measure, which are usually adjudged through post selection classification accuracy. Through these methods the ranking of genes was conducted on a single high-dimensional expression data, which led to the selection of spuriously associated and redundant genes. Hence, we developed a statistical approach through combining a support vector machine with Maximum Relevance and Minimum Redundancy under a sound statistical setup for the selection of biologically relevant genes. Here, the genes were selected through statistical significance values and computed using a nonparametric test statistic under a bootstrap-based subject sampling model. Further, a systematic and rigorous evaluation of the proposed approach with nine existing competitive methods was carried on six different real crop gene expression datasets. This performance analysis was carried out under three comparison settings, i.e., subject classification, biological relevant criteria based on quantitative trait loci and gene ontology. Our analytical results showed that the proposed approach selects genes which are more biologically relevant as compared to the existing methods. Moreover, the proposed approach was also found to be better with respect to the competitive existing methods. The proposed statistical approach provides a framework for combining filter and wrapper methods of gene selection.
The Heisenberg Indeterminacy Principle in the Context of Covariant Quantum Gravity
Authors: Tessarotto Massimo , Cremaschini Claudio
Published: October 2020

The subject of this paper deals with the mathematical formulation of the Heisenberg Indeterminacy Principle in the framework of Quantum Gravity. The starting point is the establishment of the so-called time-conjugate momentum inequalities holding for non-relativistic and relativistic Quantum Mechanics. The validity of analogous Heisenberg inequalities in quantum gravity, which must be based on strictly physically observable quantities (i.e., necessarily either 4-scalar or 4-vector in nature), is shown to require the adoption of a manifestly covariant and unitary quantum theory of the gravitational field. Based on the prescription of a suitable notion of Hilbert space scalar product, the relevant Heisenberg inequalities are established. Besides the coordinate-conjugate momentum inequalities, these include a novel proper-time-conjugate extended momentum inequality. Physical implications and the connection with the deterministic limit recovering General Relativity are investigated.
Cost-Effective High-Performance Digital Control Method in Series-Series Compensated Wireless Power Transfer System
Authors: Shin Hojoon , Chung Euihoon , Ha Jung-Ik
Published: October 2020

This paper proposes a control method for a digital signal processor based series-series (SS) compensated wireless power transfer system. In the control method, load resistance and mutual inductance are identified simultaneously, and output voltage can be estimated by using only the primary side voltage and current without direct feedback from the secondary side circuit. Since this estimation method requires a complex mathematical calculation procedure, a digital signal processor is used in this system. One of the major disadvantages of using a digital controller in this system is a limitation of sampling rates. Therefore, in this paper, several current reconstruction methods with limited sampling rates are investigated and applied. As a result, this controller not only reduces the cost of the system but also shows good estimation performance within the limited digital controller unit resource. The proposed control concept is verified by experimental results with a 48W laboratory prototype.
A New Read Scheme for Alleviating Cell-to-Cell Interference in Scaled-Down 3D NAND Flash Memory
Authors: Sim Jae-Min , Kang Myounggon , Song Yun-Heub
Published: October 2020

In this paper, we investigated the cell-to-cell interference in scaled-down 3D NAND flash memory by using a Technology Computer-Aided Design (TCAD) simulation. The fundamental cause of cell-to-cell interference is that the electric field crowding point is changed by the programmed adjacent cell so that the electric field is not sufficiently directed to the channel surface. Therefore, the channel concentration of the selected cell is changed, leading to a Vth shift. Furthermore, this phenomenon occurs more severely when the selected cell is in an erased state rather than in a programmed state. In addition, it was confirmed that the cell-to-cell interference by the programmed WLn+1 is more severe than that of WLn−1 due to the degradation of the effective mobility effect. To solve this fundamental problem, a new read scheme is proposed. Through TCAD simulation, the cell-to-cell interference was alleviated with a bias having a ΔV of 1.5 V from Vread through an optimization process to have appropriate bias conditions in three ways that are suitable for each pattern. As a result, this scheme narrowed the Vth shift of 67.5% for erased cells and narrowed the Vth shift of 70% for programmed cells. The proposed scheme is one way to solve the cell-to-cell interference that may occur as the cell-to-cell distance decreases for a high stacked 3D NAND structure.
Nutrient Contribution of Litterfall in a Short Rotation Plantation of Pure or Mixed Plots of Populus alba L. and Robinia pseudoacacia L.
Authors: González Isabel , Sixto Hortensia , Rodríguez-Soalleiro Roque , Oliveira Nerea
Published: October 2020

This study aims to quantify the potential contribution of nutrients derived from leaf litter in a short rotation coppice plantation which includes monocultures of the species Populus alba (PA) and Robina pseudoacacia (RP) as well as a mixture of 50PA:50RP, in the middle of the rotation. The P. alba monoculture was that which provided the most leaf litter (3.37 mg ha−1 yr−1), followed by the 50PA:50RP mixture (2.82 mg ha−1 yr−1) and finally the R. pseudoacacia monoculture (2.55 mg ha−1 yr−1). In addition to producing more litterfall, leaves were shed later in the P. alba monoculture later (December) than in the R. pseudoacacia monoculture (October) or the mix (throughout the fall). In terms of macronutrient supply per hectare, the contributions derived from leaf litter were higher for K, P and Mg in the case of P. alba and for N in R. pseudoacacia, the mix presenting the highest Ca content and intermediate concentrations for the rest of the nutrients. In addition, other factors such as C:N or N:MO ratios, as well as the specific characteristics of the soil, can have an important impact on the final contribution of these inputs. The carbon contribution derived from leaf fall was higher in the P. alba monoculture (1.5 mg ha−1 yr−1), intermediate in the mixed plot (1.3 mg ha−1 yr−1) and slightly lower for the R. pseudoacacia monoculture (1.3 mg ha−1 yr−1). Given these different strategies of monocultures with regard to the dynamism of the main nutrients, species mixing would appear to be suitable option to achieve a potential reduction in mineral fertilization in these plantations.
Influence of Climate on Carbon Sequestration in Conifers Growing under Contrasting Hydro-Climatic Conditions
Authors: Acosta-Hernández Andrea Cecilia , Padilla-Martínez Jaime Roberto , Hernández-Díaz José Ciro , Prieto-Ruiz José Angel , Goche-Telles José Rodolfo , Nájera-Luna Juan Abel , Pompa-García Marín
Published: October 2020

Research Highlights: Analyzing the contrasting ecological gradients makes it easier to understand the influence of climate on carbon accumulation. Background and Objectives: The increasing climatic variability has implications for vegetation, impacting on its ecological functions, among which carbon accumulation stands out. In the present study, we used climate-dendrochronology relationships to evaluate carbon accumulation in two conifer species that grow in contrasting humidity sites: Pinus strobiformis Engelm (mesic sites) and Pinus leiophylla var. chihuahuana (Engelm.) Shaw (arid sites). Materials and Methods: Using a dendrochronological approach, we estimated the correlation of biomass and carbon accumulation of each species with some climatic variables (temperature, precipitation, and a drought index) and generated a linear mixed model. Results: The response in carbon accumulation between species with respect to climate was significantly different. P. strobiformis showed a positive correlation with the climatic variables analyzed, while in P. leiophylla the correlation was negative, except with precipitation. Conclusions: These results show that forests in both mesic and arid sites are prone to climate changes, although their responses are different, impacting the productivity and carbon cycles of forest ecosystems.
Comparison of Soil Greenhouse Gas Fluxes during the Spring Freeze–Thaw Period and the Growing Season in a Temperate Broadleaved Korean Pine Forest, Changbai Mountains, China
Authors: Guo Chuying , Zhang Leiming , Li Shenggong , Li Qingkang , Dai Guanhua
Published: October 2020

Soils in mid-high latitudes are under the great impact of freeze–thaw cycling. However, insufficient research on soil CO2, CH4, and N2O fluxes during the spring freeze–thaw (SFT) period has led to great uncertainties in estimating soil greenhouse gas (GHG) fluxes. The present study was conducted in a temperate broad-leaved Korean pine mixed forest in Northeastern China, where soils experience an apparent freeze–thaw effect in spring. The temporal variations and impact factors of soil GHG fluxes were measured during the SFT period and growing season (GS) using the static-chamber method. The results show that the soil acted as a source of atmospheric CO2 and N2O and a sink of atmospheric CH4 during the whole observation period. Soil CO2 emission and CH4 uptake were lower during the SFT period than those during the GS, whereas N2O emissions were more than six times higher during the SFT period than that during the GS. The responses of soil GHG fluxes to soil temperature (Ts) and soil moisture during the SFT and GS periods differed. During the SFT period, soil CO2 and CH4 fluxes were mainly affected by the volumetric water content (VWC) and Ts, respectively, whereas soil N2O flux was influenced jointly by Ts and VWC. The dominant controlling factor for CO2 was Ts during the GS, whereas CH4 and N2O were mainly regulated by VWC. Soil CO2 and N2O fluxes accounted for 97.3% and 3.1% of the total 100-year global warming potential (GWP100) respectively, with CH4 flux offsetting 0.4% of the total GWP100. The results highlight the importance of environmental variations to soil N2O pulse during the SFT period and the difference of soil GHG fluxes between the SFT and GS periods, which contribute to predicting the forest soil GHG fluxes and their global warming potential under global climate change.