bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased Sensitivity of Detection of RASSF1A and GSTP1 DNA Fragments in Serum of Prostate Cancer Patients: Optimisation of Diagnostics Using OBBPA-ddPCR
Authors: Friedemann Markus , Horn Friederike , Gutewort Katharina , Tautz Lars , Jandeck Carsten , Bechmann Nicole , Sukocheva Olga , Wirth Manfred P. , Fuessel Susanne , Menschikowski Mario
Published: September 2021

Identification of aberrant DNA methylation is a promising tool in prostate cancer (PCa) diagnosis and treatment. In this study, we evaluated a two-step method named optimised bias-based preamplification followed by digital PCR (OBBPA-dPCR). The method was used to identify promoter hypermethylation of 2 tumour suppressor genes RASSF1A and GSTP1 in the circulating cell-free DNA (cfDNA) from serum samples of PCa patients (n = 75), benign prostatic hyperplasia (BPH, n = 58), and healthy individuals (controls, n = 155). The PCa cohort was further subdivided into subgroups comprising (I) patients with Gleason Scores (GS) ≤ 7 (n = 55), (II) GS ≥ 8 (n = 10), and (III) patients with metastatic PCa diagnosis (n = 10). We found that RASSF1A methylation levels were significantly increased in all 3 PCa subgroups compared to the controls and BPH cohorts (p < 0.01 for all comparisons). Fractional abundances of methylated GSTP1 DNA fragments were significantly increased in subgroup III of metastatic PCa patients (p < 0.001). RASSF1A methylation analysis was found to be beneficial as a complementary biomarker where further diagnostic validation is most crucial. In combination with free PSA, RASSF1A methylation status helps to identify PCa patients with GS ≥ 8 and grey-zone total PSA values between 2–10 ng/mL. In our study, PCR biases between 80–90% were sufficient to detect minute amounts of tumour DNA with high signal-to-noise ratios as well as high analytical sensitivity and specificity. Both RASSF1A and GSTP1 exhibited strongly increased DNA methylation levels in all metastatic PCa patients. Our data indicates a superior sensitivity of epigenetic biomarker analyses in early detection of PCa metastases that should also help to improve PCa therapy.
Chimeric Antigen Receptor T-Cell Therapy: The Light of Day for Osteosarcoma
Authors: Lin Zili , Wu Ziyi , Luo Wei
Published: September 2021

Osteosarcoma (OS) is the most common malignant bone tumor, arising mainly in children and adolescents. With the introduction of multiagent chemotherapy, the treatments of OS have remarkably improved, but the prognosis for patients with metastases is still poor, with a five-year survival rate of 20%. In addition, adverse effects brought by traditional treatments, including radical surgery and systemic chemotherapy, may seriously affect the survival quality of patients. Therefore, new treatments for OS await exploitation. As a novel immunotherapy, chimeric antigen receptor (CAR) T-cell therapy has achieved encouraging results in treating cancer in recent years, especially in leukemia and lymphoma. Furthermore, researchers have recently focused on CAR-T therapy in solid tumors, including OS. In this review, we summarize the safety, specificity, and clinical transformation of the targets in treating OS and point out the direction for further research.
Necroptosis in Esophageal Squamous Cell Carcinoma: An Independent Prognostic Factor and Its Correlation with Tumor-Infiltrating Lymphocytes
Authors: Yamauchi Takuro , Fujishima Fumiyoshi , Hashimoto Masatoshi , Tsunokake Junichi , Akaishi Ryujiro , Gokon Yusuke , Ueki Shunsuke , Ozawa Yohei , Fukutomi Toshiaki , Okamoto Hiroshi , Sato Chiaki , Taniyama Yusuke , Nakamura Tomohiro , Nakaya Naoki , Kamei Takashi , Sasano Hironobu
Published: September 2021

Necroptosis is a pivotal process in cancer biology; however, the clinical significance of necroptosis in esophageal squamous cell carcinoma (ESCC) has remained unknown. Therefore, in this study, we aimed to verify the potential involvement of necroptosis in the clinical outcome, chemotherapeutic resistance, and tumor microenvironment of ESCC. Mixed lineage kinase domain-like protein (MLKL) and phosphorylated MLKL (pMLKL) were immunohistochemically examined in 88 surgically resected specimens following neoadjuvant chemotherapy (NAC) and 53 pre-therapeutic biopsy specimens, respectively. Tumor-infiltrating lymphocytes (TILs) were also evaluated by immunolocalizing CD3, CD8, and forkhead box protein 3 (FOXP3) in the residual tumors after NAC. High pMLKL status in the post-NAC resected specimens was significantly correlated with worse prognosis in ESCC patients. Multivariate analysis demonstrated that a high pMLKL status was an independent prognostic factor. In pre-NAC biopsy specimens, a high pMLKL status was significantly associated with a lower therapeutic efficacy. CD8+ TILs were significantly lower in the high-pMLKL group. FOXP3+ TILs were significantly higher in both high-MLKL and high-pMLKL groups. We first demonstrated pMLKL status as an independent prognostic factor in ESCC patients. Our study revealed the possible involvement of necroptosis in the immunosuppressive microenvironment, resulting in the attenuated therapeutic efficacy of NAC and eventual adverse clinical outcomes in ESCC.
Colorectal Cancer Screening Outcomes of 2412 Prostate Cancer Patients Considered for Carbon Ion Radiotherapy
Authors: Kobayashi Nao , Oike Takahiro , Kubo Nobuteru , Miyasaka Yuhei , Mizukami Tatsuji , Sato Hiro , Adachi Akiko , Katoh Hiroyuki , Kawamura Hidemasa , Ohno Tatsuya
Published: September 2021

Colorectal cancer (CRC) screening is effective for detecting cancer in average-risk adults. For prostate cancer (PCa) patients considered for carbon ion radiotherapy (CIRT), pre-treatment CRC screening is performed empirically to avoid post-treatment colonoscopic manipulation. However, the outcomes of screening this population remain unclear. Here, we compared the outcomes of routine pre-CIRT CRC screening of 2412 PCa patients at average risk for CRC with data from two published datasets: the Japan National Cancer Registry (JNCR) and a series of 17 large-scale screening studies analyzing average-risk adults. The estimated prevalence rate was calculated using the pooled sensitivity elucidated by a previous meta-analysis. Consequently, 28 patients (1.16%) were diagnosed with CRC. CRC morbidity was significantly associated with high pre-treatment levels of prostate-specific antigen (p = 0.023). The screening positivity rate in this study cohort exceeded the annual incidence reported in the JNCR for most age brackets. Furthermore, the estimated prevalence rate in this study cohort (1.46%) exceeded that reported in all 17 large-scale studies, making the result an outlier (p = 0.005). These data indicate the possibility that the prevalence of CRC in PCa patients is greater than that in general average-risk adults, warranting further research in a prospective setting.
A Comprehensive Evaluation and Benchmarking of Convolutional Neural Networks for Melanoma Diagnosis
Authors: Alzahrani Saeed , Al-Bander Baidaa , Al-Nuaimy Waleed
Published: September 2021

Melanoma is the most invasive skin cancer with the highest risk of death. While it is a serious skin cancer, it is highly curable if detected early. Melanoma diagnosis is difficult, even for experienced dermatologists, due to the wide range of morphologies in skin lesions. Given the rapid development of deep learning algorithms for melanoma diagnosis, it is crucial to validate and benchmark these models, which is the main challenge of this work. This research presents a new benchmarking and selection approach based on the multi-criteria analysis method (MCDM), which integrates entropy and the preference ranking organization method for enrichment of evaluations (PROMETHEE) methods. The experimental study is carried out in four phases. Firstly, 19 convolution neural networks (CNNs) are trained and evaluated on a public dataset of 991 dermoscopic images. Secondly, to obtain the decision matrix, 10 criteria, including accuracy, classification error, precision, sensitivity, specificity, F1-score, false-positive rate, false-negative rate, Matthews correlation coefficient (MCC), and the number of parameters are established. Third, entropy and PROMETHEE methods are integrated to determine the weights of criteria and rank the models. Fourth, the proposed benchmarking framework is validated using the VIKOR method. The obtained results reveal that the ResNet101 model is selected as the optimal diagnosis model for melanoma in our case study data. Thus, the presented benchmarking framework is proven to be useful at exposing the optimal melanoma diagnosis model targeting to ease the selection process of the proper convolutional neural network architecture.
Effects of Obesogenic Feeding and Free Fatty Acids on Circadian Secretion of Metabolic Hormones: Implications for the Development of Type 2 Diabetes
Authors: Martchenko Alexandre , Brubaker Patricia Lee
Published: September 2021

Circadian rhythms are 24-h internal biological rhythms within organisms that govern virtually all aspects of physiology. Interestingly, metabolic tissues have been found to express cell-autonomous clocks that govern their rhythmic activity throughout the day. Disruption of normal circadian rhythmicity, as induced by environmental factors such as shift work, significantly increases the risk for the development of metabolic diseases, including type 2 diabetes and obesity. More recently, obesogenic feeding and its fatty acid components have also been shown to be potent disruptors of normal circadian biology. Two key hormones that are released in response to nutrient intake are the anti-diabetic incretin hormone glucagon-like peptide-1, from intestinal L cells, and insulin secreted by pancreatic β cells, both of which are required for the maintenance of metabolic homeostasis. This review will focus on the circadian function of the L and β cells and how both obesogenic feeding and the saturated fatty acid, palmitate, affect their circadian clock and function. Following introduction of the core biological clock and the hierarchical organization of the mammalian circadian system, the circadian regulation of normal L and β cell function and the importance of GLP-1 and insulin in establishing metabolic control are discussed. The central focus of the review then considers the circadian-disrupting effects of obesogenic feeding and palmitate exposure in L and β cells, while providing insight into the potential causative role in the development of metabolic disease.
Dissecting Highly Mutagenic Processing of Complex Clustered DNA Damage in Yeast Saccharomyces cerevisiae
Authors: Kozmin Stanislav G. , Eot-Houllier Gregory , Reynaud-Angelin Anne , Gasparutto Didier , Sage Evelyne
Published: September 2021

Clusters of DNA damage, also called multiply damaged sites (MDS), are a signature of ionizing radiation exposure. They are defined as two or more lesions within one or two helix turns, which are created by the passage of a single radiation track. It has been shown that the clustering of DNA damage compromises their repair. Unresolved repair may lead to the formation of double-strand breaks (DSB) or the induction of mutation. We engineered three complex MDS, comprised of oxidatively damaged bases and a one-nucleotide (1 nt) gap (or not), in order to investigate the processing and the outcome of these MDS in yeast Saccharomyces cerevisiae. Such MDS could be caused by high linear energy transfer (LET) radiation. Using a whole-cell extract, deficient (or not) in base excision repair (BER), and a plasmid-based assay, we investigated in vitro excision/incision at the damaged bases and the mutations generated at MDS in wild-type, BER, and translesion synthesis-deficient cells. The processing of the studied MDS did not give rise to DSB (previously published). Our major finding is the extremely high mutation frequency that occurs at the MDS. The proposed processing of MDS is rather complex, and it largely depends on the nature and the distribution of the damaged bases relative to the 1 nt gap. Our results emphasize the deleterious consequences of MDS in eukaryotic cells.
Genomic Aberrations Associated with the Pathophysiological Mechanisms of Neurodevelopmental Disorders
Authors: Yamamoto Toshiyuki
Published: September 2021

Genomic studies are increasingly revealing that neurodevelopmental disorders are caused by underlying genomic alterations. Chromosomal microarray testing has been used to reliably detect minute changes in genomic copy numbers. The genes located in the aberrated regions identified in patients with neurodevelopmental disorders may be associated with the phenotypic features. In such cases, haploinsufficiency is considered to be the mechanism, when the deletion of a gene is related to neurodevelopmental delay. The loss-of-function mutation in such genes may be evaluated using next-generation sequencing. On the other hand, the patients with increased copy numbers of the genes may exhibit different clinical symptoms compared to those with loss-of-function mutation in the genes. In such cases, the additional copies of the genes are considered to have a dominant negative effect, inducing cell stress. In other cases, not the copy number changes, but mutations of the genes are responsible for causing the clinical symptoms. This can be explained by the dominant negative effects of the gene mutations. Currently, the diagnostic yield of genomic alterations using comprehensive analysis is less than 50%, indicating the existence of more subtle alterations or genomic changes in the untranslated regions. Copy-neutral inversions and insertions may be related. Hence, better analytical algorithms specialized for the detection of such alterations are required for higher diagnostic yields.
Biosynthesis of the Novel Endogenous 15-Lipoxygenase Metabolites N-13-Hydroxy-octodecadienoyl-ethanolamine and 13-Hydroxy-octodecadienoyl-glycerol by Human Neutrophils and Eosinophils
Authors: Archambault Anne-Sophie , Tinto Francesco , Dumais Élizabeth , Rakotoarivelo Volatiana , Kostrzewa Magdalena , Plante Pier-Luc , Martin Cyril , Simard Mélissa , Silvestri Cristoforo , Pouliot Roxane , Laviolette Michel , Boulet Louis-Philippe , Vitale Rosa Maria , Ligresti Alessia , Di Marzo Vincenzo , Flamand Nicolas
Published: September 2021

The endocannabinoids 2-arachidonoyl-glycerol and N-arachidonoyl-ethanolamine are lipids regulating many physiological processes, notably inflammation. Endocannabinoid hydrolysis inhibitors are now being investigated as potential anti-inflammatory agents. In addition to 2-arachidonoyl-glycerol and N-arachidonoyl-ethanolamine, the endocannabinoidome also includes other monoacylglycerols and N-acyl-ethanolamines such as 1-linoleoyl-glycerol (1-LG) and N-linoleoyl-ethanolamine (LEA). By increasing monoacylglycerols and/or N-acyl-ethanolamine levels, endocannabinoid hydrolysis inhibitors will likely increase the levels of their metabolites. Herein, we investigated whether 1-LG and LEA were substrates for the 15-lipoxygenase pathway, given that both possess a 1Z,4Z-pentadiene motif, near their omega end. We thus assessed how human eosinophils and neutrophils biosynthesized the 15-lipoxygenase metabolites of 1-LG and LEA. Linoleic acid (LA), a well-documented substrate of 15-lipoxygenases, was used as positive control. N-13-hydroxy-octodecadienoyl-ethanolamine (13-HODE-EA) and 13-hydroxy-octodecadienoyl-glycerol (13-HODE-G), the 15-lipoxygenase metabolites of LEA and 1-LG, were synthesized using Novozym 435 and soybean lipoxygenase. Eosinophils, which express the 15-lipoxygenase-1, metabolized LA, 1-LG, and LEA into their 13-hydroxy derivatives. This was almost complete after five minutes. Substrate preference of eosinophils was LA > LEA > 1-LG in presence of 13-HODE-G hydrolysis inhibition with methyl-arachidonoyl-fluorophosphonate. Human neutrophils also metabolized LA, 1-LG, and LEA into their 13-hydroxy derivatives. This was maximal after 15–30 s. Substrate preference was LA ≫ 1-LG > LEA. Importantly, 13-HODE-G was found in humans and mouse tissue samples. In conclusion, our data show that human eosinophils and neutrophils metabolize 1-LG and LEA into the novel endogenous 15-lipoxygenase metabolites 13-HODE-G and 13-HODE-EA. The full biological importance of 13-HODE-G and 13-HODE-EA remains to be explored.
Elevated CO2 Concentration Alters Photosynthetic Performances under Fluctuating Light in Arabidopsis thaliana
Authors: Tan Shun-Ling , Huang Xing , Li Wei-Qi , Zhang Shi-Bao , Huang Wei
Published: September 2021

In view of the current and expected future rise in atmospheric CO2 concentrations, we examined the effect of elevated CO2 on photoinhibition of photosystem I (PSI) under fluctuating light in Arabidopsis thaliana. At 400 ppm CO2, PSI showed a transient over-reduction within the first 30 s after transition from dark to actinic light. Under the same CO2 conditions, PSI was highly reduced after a transition from low to high light for 20 s. However, such PSI over-reduction greatly decreased when measured in 800 ppm CO2, indicating that elevated atmospheric CO2 facilitates the rapid oxidation of PSI under fluctuating light. Furthermore, after fluctuating light treatment, residual PSI activity was significantly higher in 800 ppm CO2 than in 400 ppm CO2, suggesting that elevated atmospheric CO2 mitigates PSI photoinhibition under fluctuating light. We further demonstrate that elevated CO2 does not affect PSI activity under fluctuating light via changes in non-photochemical quenching or cyclic electron transport, but rather from a rapid electron sink driven by CO2 fixation. Therefore, elevated CO2 mitigates PSI photoinhibition under fluctuating light at the acceptor rather than the donor side. Taken together, these observations indicate that elevated atmospheric CO2 can have large effects on thylakoid reactions under fluctuating light.
CAR T-Cells Depend on the Coupling of NADH Oxidation with ATP Production
Authors: Garcia-Canaveras Juan , Heo David , Trefely Sophie , Leferovich John , Xu Chong , Philipson Benjamin , Ghassemi Saba , Milone Michael , Moon Edmund , Snyder Nathaniel , June Carl , Rabinowitz Joshua , O’Connor Roddy
Published: September 2021

The metabolic milieu of solid tumors provides a barrier to chimeric antigen receptor (CAR) T-cell therapies. Excessive lactate or hypoxia suppresses T-cell growth, through mechanisms including NADH buildup and the depletion of oxidized metabolites. NADH is converted into NAD+ by the enzyme Lactobacillus brevis NADH Oxidase (LbNOX), which mimics the oxidative function of the electron transport chain without generating ATP. Here we determine if LbNOX promotes human CAR T-cell metabolic activity and antitumor efficacy. CAR T-cells expressing LbNOX have enhanced oxygen as well as lactate consumption and increased pyruvate production. LbNOX renders CAR T-cells resilient to lactate dehydrogenase inhibition. But in vivo in a model of mesothelioma, CAR T-cell’s expressing LbNOX showed no increased antitumor efficacy over control CAR T-cells. We hypothesize that T cells in hostile environments face dual metabolic stressors of excessive NADH and insufficient ATP production. Accordingly, futile T-cell NADH oxidation by LbNOX is insufficient to promote tumor clearance.
Ternary Holey Carbon Nanohorns/TiO2/PVP Nanohybrids as Sensing Films for Resistive Humidity Sensors
Authors: Serban Bogdan-Catalin , Buiu Octavian , Bumbac Marius , Dumbravescu Niculae , Avramescu Viorel , Brezeanu Mihai , Radulescu Cristiana , Craciun Gabriel , Nicolescu Cristina Mihaela , Romanitan Cosmin , Comanescu Florin
Published: September 2021

In this paper, we present the relative humidity (RH) sensing response of a chemiresistive sensor, employing sensing layers based on a ternary nanohybrids comprised of holey carbon nanohorns (CNHox), titanium (IV) oxide, and polyvinylpyrrolidone (PVP) at 1/1/1/(T1), 2/1/1/(T2), and with 3/1/1 (T3) mass ratios. The sensing device is comprised of a silicon-based substrate, a SiO2 layer, and interdigitated transducer (IDT) electrodes. The sensitive layer was deposited via the drop-casting method on the sensing structure, followed by a two-step annealing process. The structure and composition of the sensing films were investigated through scanning electron microscopy (SEM), Raman spectroscopy, and X-ray diffraction (XRD). The resistance of the ternary nanohybrid-based sensing layer increases when H increases between 0% and 80%. A different behavior of the sensitive layers is registered when the humidity increases from 80% to 100%. Thus, the resistance of the T1 sensor slightly decreases with increasing humidity, while the resistance of sensors T2 and T3 register an increase in resistance with increasing humidity. The T2 and T3 sensors demonstrate a good linearity for the entire (0–100%) RH range, while for T1, the linear behavior is limited to the 0–80% range. Their overall room temperature response is comparable to a commercial humidity sensor, characterized by a good sensitivity, a rapid response, and fast recovery times. The functional role for each of the components of the ternary CNHox/TiO2/PVP nanohybrid is explained by considering issues such as their electronic properties, affinity for water molecules, and internal pore accessibility. The decreasing number of holes in the carbonaceous component at the interaction with water molecules, with the protonic conduction (Grotthus mechanism), and with swelling were analyzed to evaluate the sensing mechanism. The hard–soft acid-base (HSAB) theory also has proven to be a valuable tool for understanding the complex interaction of the ternary nanohybrid with moisture.
Influence of Double-Pulse Electrodeposition Parameters on the Performance of Nickel/Nanodiamond Composite Coatings
Authors: Wang Dongai , Liu Meihua , Zhu Yuanmin , Li Feihui
Published: September 2021

In this study, using 45# carbon steel as the substrate, a first experimental analysis was carried out on the polarisation behaviour of different component wattage plating solutions in order to determine the reasonable content of nanodiamond particles in a nickel/nanodiamond composite plating solution. Secondly, the effect of double-pulse forward and reverse duty cycle and reverse working time on the performance of nickel/nanodiamond composite plating was then investigated by testing the thickness, hardness and surface roughness of the composite plating and observing the surface micromorphology. The experimental results show that, when the content of nanodiamond particles in the plating solution is 5 g/L, the anti-pulse working time, forward and reverse pulse duty cycle of the double-pulse plating parameters are 20 ms, 0.3 and 0.2, respectively, and the composite plating layer prepared by double pulse has good comprehensive performance. This research work provides technical support for the optimisation of process parameters for the preparation of nickel/nanodiamond composite coatings by double-pulse electrodeposition.
Growth of Acetaminophen Polymorphic Crystals and Solution-Mediated Phase Transition from Trihydrate to Form II in Agarose Gel
Authors: Nishigaki Akari , Maruyama Mihoko , Tanaka Shun-ichi , Yoshikawa Hiroshi Y. , Imanishi Masayuki , Yoshimura Masashi , Mori Yusuke , Takano Kazufumi
Published: September 2021

The growth of acetaminophen polymorphic crystals and the solution-mediated phase transition from trihydrate to form II in agarose gel were investigated. The form II crystals grown in gels, presumably because of the agarose content, dissolved less rapidly at high temperatures and were more stable than in water. The trihydrate crystals in the gel were also expected to be stabilized by containing agarose, but in fact the fine morphology resulted in reduced stability. The solution-mediated phase transition from trihydrate to form II via form II seeding took longer in the gel because the gel slowed down the dissolution of the trihydrate by hindering the dispersion of the form II seeds and delayed the growth of form II by reducing the diffusion rate of the molecules dissolved from the trihydrate. Delays in solution-mediated phase transition and changes in stability for crystals grown in gels indicate the effectiveness of gels in controlling polymorphisms in pharmaceutical compounds.
New Insights into the Biology and Diagnosis of Splenic Marginal Zone Lymphomas
Authors: Donzel Marie , Baseggio Lucile , Fontaine Juliette , Pesce Florian , Ghesquières Hervé , Bachy Emmanuel , Verney Aurélie , Traverse-Glehen Alexandra
Published: September 2021

Splenic marginal zone lymphoma (SMZL) is a small B-cell lymphoma, which has been recognized as a distinct pathological entity since the WHO 2008 classification. It classically presents an indolent evolution, but a third of patients progress rapidly and require aggressive treatments, such as immuno-chemotherapy or splenectomy, with all associated side effects. In recent years, advances in the comprehension of SMZL physiopathology have multiplied, thanks to the arrival of new devices in the panel of available molecular biology techniques, allowing the discovery of new molecular findings. In the era of targeted therapies, an update of current knowledge is needed to guide future researches, such as those on epigenetic modifications or the microenvironment of these lymphomas.
The Influence of Maternal Cell Contamination on Fetal Aneuploidy Detection Using Chip-Based Digital PCR Testing
Authors: Nykel Anna , Woźniak Rafał , Gach Agnieszka
Published: September 2021

Prenatal samples obtained by amniocentesis or chorionic villus sampling are at risk of maternal cell contamination (MCC). In traditional prenatal analysis, MCC is recommended to be assayed by special tests, such as the short tandem repeat analysis and, if detected at a high level, may result in failed analysis report. The objective of this study was to test the ability of chip-based digital PCR to detect fetal aneuploidies in the presence of MCC. To determine the level of accuracy of MCC detection, an aneuploid male sample was subjected to serial dilution with an euploid female sample. DNA was extracted from prenatal samples and analyzed with QuantStudio 3D Digital PCR. Digital PCR analysis allowed the detection of trisomy 21, trisomy 18, and X monosomy accurately in samples with 90%, 85%, and 92% of MCC, respectively. Moreover, our results indicated that digital PCR was able to accurately confirm the presence of Y chromosome at up to 95% contamination. The amniotic fluid and chorionic villus sampling (CVS) received in our clinical laboratory was subjected to further analysis of MCC based on the aneuploidy assessment algorithm, resulting in the identification of 10 contaminated samples and four cases of true fetal mosaicism. We conclude that chip-based digital PCR analysis enables the detection of fetal aneuploidy with high levels of accuracy, even in cases of significant MCC. Importantly, the algorithm eliminates the need for maternal DNA and additional MCC tests, which reduces costs and simplifies the diagnostic procedure. The method is easy to set up and suitable for routine clinical practice.
A Low-Dose CT-Based Radiomic Model to Improve Characterization and Screening Recall Intervals of Indeterminate Prevalent Pulmonary Nodules
Authors: Rundo Leonardo , Ledda Roberta Eufrasia , di Noia Christian , Sala Evis , Mauri Giancarlo , Milanese Gianluca , Sverzellati Nicola , Apolone Giovanni , Gilardi Maria Carla , Messa Maria Cristina , Castiglioni Isabella , Pastorino Ugo
Published: September 2021

Lung cancer (LC) is currently one of the main causes of cancer-related deaths worldwide. Low-dose computed tomography (LDCT) of the chest has been proven effective in secondary prevention (i.e., early detection) of LC by several trials. In this work, we investigated the potential impact of radiomics on indeterminate prevalent pulmonary nodule (PN) characterization and risk stratification in subjects undergoing LDCT-based LC screening. As a proof-of-concept for radiomic analyses, the first aim of our study was to assess whether indeterminate PNs could be automatically classified by an LDCT radiomic classifier as solid or sub-solid (first-level classification), and in particular for sub-solid lesions, as non-solid versus part-solid (second-level classification). The second aim of the study was to assess whether an LCDT radiomic classifier could automatically predict PN risk of malignancy, and thus optimize LDCT recall timing in screening programs. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), accuracy, positive predictive value, negative predictive value, sensitivity, and specificity. The experimental results showed that an LDCT radiomic machine learning classifier can achieve excellent performance for characterization of screen-detected PNs (mean AUC of 0.89 ± 0.02 and 0.80 ± 0.18 on the blinded test dataset for the first-level and second-level classifiers, respectively), providing quantitative information to support clinical management. Our study showed that a radiomic classifier could be used to optimize LDCT recall for indeterminate PNs. According to the performance of such a classifier on the blinded test dataset, within the first 6 months, 46% of the malignant PNs and 38% of the benign ones were identified, improving early detection of LC by doubling the current detection rate of malignant nodules from 23% to 46% at a low cost of false positives. In conclusion, we showed the high potential of LDCT-based radiomics for improving the characterization and optimizing screening recall intervals of indeterminate PNs.
Late Changes in the Extracellular Matrix of the Bladder after Radiation Therapy for Pelvic Tumors
Authors: Streltsova Olga , Kiseleva Elena , Dudenkova Varvara , Sergeeva Ekaterina , Tararova Ekaterina , Kochueva Marina , Kotova Svetlana , Timofeeva Victoriya , Yunusova Katerina , Bavrina Anna , Timashev Peter , Solovieva Anna , Maslennikova Anna
Published: September 2021

Radiation therapy is one of the cardinal approaches in the treatment of malignant tumors of the pelvis. It leads to the development of radiation-induced complications in the normal tissues. Thus, the evaluation of radiation-induced changes in the extracellular matrix of the normal tissue is deemed urgent, since connective tissue stroma degradation plays a crucial role in the development of Grade 3–4 adverse effects (hemorrhage, necrosis, and fistula). Such adverse effects not only drastically reduce the patients’ quality of life but can also become life-threatening. The aim of this study is to quantitatively analyze the bladder collagen state in patients who underwent radiation therapy for cervical and endometrial cancer and in patients with chronic bacterial cystitis and compare them to the normal bladder extracellular matrix. Materials and methods: One hundred and five patients with Grade 2–4 of radiation cystitis, 67 patients with bacterial chronic cystitis, and 20 volunteers without bladder pathology were enrolled. Collagen changes were evaluated depending on its hierarchical level: fibrils and fibers level by atomic force microscopy; fibers and bundles level by two-photon microscopy in the second harmonic generation (SHG) mode; general collagen architectonics by cross-polarization optical coherence tomography (CP OCT). Results: The main sign of the radiation-induced damage of collagen fibrils and fibers was the loss of the ordered “basket-weave” packing and a significant increase in the total area of ruptures deeper than 1 µm compared to the intact sample. The numerical analysis of SHG images detected that a decrease in the SHG signal intensity of collagen is correlated with the increase in the grade of radiation cystitis. The OCT signal brightness in cross-polarization images demonstrated a gradual decrease compared to the intact bladder depending on the grade of the adverse event. Conclusions: The observed correspondence between the extracellular matrix changes at the microscopic level and at the level of the general organ architectonics allows for the consideration of CP OCT as a method of “optical biopsy” in the grading of radiation-induced collagen damage.
Automated Final Lesion Segmentation in Posterior Circulation Acute Ischemic Stroke Using Deep Learning
Authors: Zoetmulder Riaan , Konduri Praneeta R. , Obdeijn Iris V. , Gavves Efstratios , Išgum Ivana , Majoie Charles B.L.M. , Dippel Diederik W.J. , Roos Yvo B.W.E.M. , Goyal Mayank , Mitchell Peter J. , Campbell Bruce C. V. , Lopes Demetrius K. , Reimann Gernot , Jovin Tudor G. , Saver Jeffrey L. , Muir Keith W. , White Phil , Bracard Serge , Chen Bailiang , Brown Scott , Schonewille Wouter J. , van der Hoeven Erik , Puetz Volker , Marquering Henk A.
Published: September 2021

Final lesion volume (FLV) is a surrogate outcome measure in anterior circulation stroke (ACS). In posterior circulation stroke (PCS), this relation is plausibly understudied due to a lack of methods that automatically quantify FLV. The applicability of deep learning approaches to PCS is limited due to its lower incidence compared to ACS. We evaluated strategies to develop a convolutional neural network (CNN) for PCS lesion segmentation by using image data from both ACS and PCS patients. We included follow-up non-contrast computed tomography scans of 1018 patients with ACS and 107 patients with PCS. To assess whether an ACS lesion segmentation generalizes to PCS, a CNN was trained on ACS data (ACS-CNN). Second, to evaluate the performance of only including PCS patients, a CNN was trained on PCS data. Third, to evaluate the performance when combining the datasets, a CNN was trained on both datasets. Finally, to evaluate the performance of transfer learning, the ACS-CNN was fine-tuned using PCS patients. The transfer learning strategy outperformed the other strategies in volume agreement with an intra-class correlation of 0.88 (95% CI: 0.83–0.92) vs. 0.55 to 0.83 and a lesion detection rate of 87% vs. 41–77 for the other strategies. Hence, transfer learning improved the FLV quantification and detection rate of PCS lesions compared to the other strategies.
Human TERT Promoter Mutations in Atypical and Anaplastic Meningiomas
Authors: Mellai Marta , Porrini Prandini Omar , Mustaccia Aurora , Fogazzi Valentina , Allesina Marta , Krengli Marco , Boldorini Renzo
Published: September 2021

Background: The role of telomerase reverse transcriptase (TERT) gene promoter mutations (pTERT) in atypical and anaplastic meningiomas remains controversial. This study aimed to evaluate their impact on the histologic diagnosis and prognosis in a retrospective series of 74 patients with atypical and anaplastic meningioma, including disease progression and relapse. A supplementary panel of 21 benign tumours was used as a control cohort. Materials and Methods: The mutation rate of the pTERT gene was assessed by Sanger sequencing. ATRX protein expression was detected by immunohistochemistry. The phenotypic and genotypic intra-tumour heterogeneity was studied in a sub-group of 12 cases using a Molecular Machines & Industries (MMI) CellCut laser microdissection (LMD) system. Results: pTERT mutations were detected in 12/74 (17.6%) malignant meningiomas. The mutation rate was significantly higher in anaplastic meningiomas (7/23, 30.4%) compared to atypical tumours (5/48, 10.4%) (p = 0.0443). In contrast, the mutation rate was < 5% in benign tumours. All pTERT mutant cases retained nuclear ATRX immunoreactivity. pTERT mutations were significantly associated with the histologic grade (p = 0.0443) and were adverse prognostic factors for anaplastic tumours (p = 0.06). Conclusion: We reported on the pTERT mutation spectrum in malignant meningiomas, supporting their use in the prognostic classification.
Metastatic Pulmonary Calcification Detected on 18F-FDG PET/CT and 99mTc-MDP Bone Scan
Authors: Cheon Miju , Yoo Jang
Published: September 2021

Metastatic calcification relates to abnormal calcification resulting from hypercalcemia and can affect soft tissues, skeletal muscle, myocardium, lungs, stomach, kidneys, and blood vessels. We describe a case of metastatic pulmonary calcification in a 71-year-old male, images with 18F-fluorodeoxyglucose (FDG) PET/CT and 99mTc- methylene diphosphonate (MDP) bone scan.
Reliable Recurrence Algorithm for High-Order Krawtchouk Polynomials
Authors: AL-Utaibi Khaled A. , Abdulhussain Sadiq H. , Mahmmod Basheera M. , Naser Marwah Abdulrazzaq , Alsabah Muntadher , Sait Sadiq M.
Published: September 2021

Krawtchouk polynomials (KPs) and their moments are promising techniques for applications of information theory, coding theory, and signal processing. This is due to the special capabilities of KPs in feature extraction and classification processes. The main challenge in existing KPs recurrence algorithms is that of numerical errors, which occur during the computation of the coefficients in large polynomial sizes, particularly when the KP parameter (p) values deviate away from 0.5 to 0 and 1. To this end, this paper proposes a new recurrence relation in order to compute the coefficients of KPs in high orders. In particular, this paper discusses the development of a new algorithm and presents a new mathematical model for computing the initial value of the KP parameter. In addition, a new diagonal recurrence relation is introduced and used in the proposed algorithm. The diagonal recurrence algorithm was derived from the existing n direction and x direction recurrence algorithms. The diagonal and existing recurrence algorithms were subsequently exploited to compute the KP coefficients. First, the KP coefficients were computed for one partition after dividing the KP plane into four. To compute the KP coefficients in the other partitions, the symmetry relations were exploited. The performance evaluation of the proposed recurrence algorithm was determined through different comparisons which were carried out in state-of-the-art works in terms of reconstruction error, polynomial size, and computation cost. The obtained results indicate that the proposed algorithm is reliable and computes lesser coefficients when compared to the existing algorithms across wide ranges of parameter values of p and polynomial sizes N. The results also show that the improvement ratio of the computed coefficients ranges from 18.64% to 81.55% in comparison to the existing algorithms. Besides this, the proposed algorithm can generate polynomials of an order ∼8.5 times larger than those generated using state-of-the-art algorithms.
Time Series Modelling
Authors: Weiß Christian H.
Published: September 2021

Time series consist of data observed sequentially in time, and they are assumed to stem from an underlying stochastic process [...]
CSI Amplitude Fingerprinting for Indoor Localization with Dictionary Learning
Authors: Liu Wen , Wang Xu , Deng Zhongliang
Published: September 2021

With the rapid growth of the demand for location services in the indoor environment, fingerprint-based indoor positioning has attracted widespread attention due to its high-precision characteristics. This paper proposes a double-layer dictionary learning algorithm based on channel state information (DDLC). The DDLC system includes two stages. In the offline training stage, a two-layer dictionary learning architecture is constructed for the complex conditions of indoor scenes. In the first layer, for the input training data of different regions, multiple sub-dictionaries are generated corresponding to learning, and non-coherent promotion items are added to emphasize the discrimination between sparse coding in different regions. The second-level dictionary learning introduces support vector discriminant items for the fingerprint points inside each region, and uses Max-margin to distinguish different fingerprint points. In the online positioning stage, we first determine the area of the test point based on the reconstruction error, and then use the support vector discriminator to complete the fingerprint matching work. In this experiment, we selected two representative indoor positioning environments, and compared the DDLC with several existing indoor positioning methods. The results show that DDLC can effectively reduce positioning errors, and because the dictionary itself is easy to maintain and update, the characteristic of strong anti-noise ability can be better used in CSI indoor positioning work.
Ordinal Time Series Forecasting of the Air Quality Index
Authors: Chen Cathy W. S. , Chiu L. M.
Published: September 2021

This research models and forecasts daily AQI (air quality index) levels in 16 cities/counties of Taiwan, examines their AQI level forecast performance via a rolling window approach over a one-year validation period, including multi-level forecast classification, and measures the forecast accuracy rates. We employ statistical modeling and machine learning with three weather covariates of daily accumulated precipitation, temperature, and wind direction and also include seasonal dummy variables. The study utilizes four models to forecast air quality levels: (1) an autoregressive model with exogenous variables and GARCH (generalized autoregressive conditional heteroskedasticity) errors; (2) an autoregressive multinomial logistic regression; (3) multi-class classification by support vector machine (SVM); (4) neural network autoregression with exogenous variable (NNARX). These models relate to lag-1 AQI values and the previous day’s weather covariates (precipitation and temperature), while wind direction serves as an hour-lag effect based on the idea of nowcasting. The results demonstrate that autoregressive multinomial logistic regression and the SVM method are the best choices for AQI-level predictions regarding the high average and low variation accuracy rates.
Consideration for Affects of an XOR in a Random Number Generator Using Ring Oscillators
Authors: Sato Ryoichi , Kodera Yuta , Ali Md. Arshad , Kusaka Takuya , Nogami Yasuyuki , Morelos-Zaragoza Robert H.
Published: September 2021

A cloud service to offer entropy has been paid much attention to. As one of the entropy sources, a physical random number generator is used as a true random number generator, relying on its irreproducibility. This paper focuses on a physical random number generator using a field-programmable gate array as an entropy source by employing ring oscillator circuits as a representative true random number generator. This paper investigates the effects of an XOR gate in the oscillation circuit by observing the output signal period. It aims to reveal the relationship between inputs and the output through the XOR gate in the target generator. The authors conduct two experiments to consider the relevance. It is confirmed that combining two ring oscillators with an XOR gate increases the complexity of the output cycle. In addition, verification using state transitions showed that the probability of the state transitions was evenly distributed by increasing the number of ring oscillator circuits.
Lumped Parameter Model and Electromagnetic Performance Analysis of a Single-Sided Variable Flux Permanent Magnet Linear Machine
Authors: Ullah Basharat , Khan Faisal , Qasim Muhammad , Khan Bakhtiar , Milyani Ahmad H. , Cheema Khalid Mehmood , Din Zakiud
Published: September 2021

A new Single-sided Variable Flux Permanent Magnet Linear Machine with flux bridge in mover core is proposed in this paper. The flux bridge prevents the leakage flux from the mover and converts it into flux linkage, which greatly influences the performance of the machine. First, a lumped parameter model is used to find the suitable coil combination and no-load flux linkage of the proposed machine, which greatly reduces the computational time and drive storage. Secondly, the proposed machine replaces the expensive rare earth permanent magnets with ferrite magnets and provides improved flux controlling capability under variable excitation currents. Multivariable geometric optimization is utilized to optimize the leading design parameters like split ratio, stator pole width, width and height of permanent magnet, flux bridge width, the width of mover’s tooth, and stator slot depth at constant electric and magnetic loading. The optimized design increases the flux linkage by 44.11%, average thrust force by 35%, thrust force density by 35.02%, minimizes ripples in thrust force by 23%, and detent force by 87.5%. Furthermore, the results obtained by 2D analysis are verified by 3D analysis. Thermal analysis is done to set the operating limit of the proposed machine.
Contractual Systems in the Oil and Gas Sector: Current Status and Development
Authors: Dirani Fatima , Ponomarenko Tatiana
Published: September 2021

Production activities in the oil and gas industry are capital-intensive and associated with high technology, with these assets not always being available to oil-producing countries or national companies. Any form of interaction between the parties involved in natural resource extraction requires clear regulation regarding contractual relationships. This study attempts to analyze Indonesia’s production sharing contract system in order to assess its applicability to other conditions. The article covers the key aspects of contract theory, provides a classification of contractual systems in the oil and gas sector, and discusses the most common types of contractual agreements. It also considers the key principles of production sharing contracts (PSCs), analyzes the development of PSC practices in Indonesia over the past sixty years, and highlights PSC advantages and disadvantages.
Smart and Renewable Energy System to Power a Temperature-Controlled Greenhouse
Authors: Riahi Jamel , Vergura Silvano , Mezghani Dhafer , Mami Abdelkader
Published: September 2021

This paper presents the modeling and simulation of a Multi-Source Power System (MSPS)—composed of two renewable energy sources and supported by a Battery Energy Storage System (BESS)—to supply the ventilation and heating system for a temperature-controlled agricultural greenhouse. The first one is a photovoltaic (PV) generator connected to a DC/AC inverter and the second one is a wind turbine connected to a Permanent Magnet Synchronous Generator (PMSG). The temperature contribution in the model of the PV generator is deeply studied. A Maximum Power Point Tracking (MPPT) control based on fuzzy logic is used to drive a SEPIC converter to feed the maximum power to the greenhouse actuators. The operation of the actuators (ventilation and heating systems), on the basis of the mismatch between the internal temperature and the reference one, is controlled by a PI controller optimized by fuzzy logic, for more robust results. The simulation of the system is carried out in a Matlab/Simulink environment and its validation is based on the comparison between the simulated and experimental data for a test greenhouse, located in the Faculty of Science in Tunis. The results show that the proposed system provides an efficient solution for controlling the microclimate of the agricultural greenhouse in different periods of the year.