bluuebunny/crossref_metadata_2025 huggingface dataset:
A Systematic Mapping of the Advancing Use of Machine Learning Techniques for Predictive Maintenance in the Manufacturing Sector
Authors: Nacchia Milena , Fruggiero Fabio , Lambiase Alfredo , Bruton Ken
Published: March 2021

The increasing availability of data, gathered by sensors and intelligent machines, is changing the way decisions are made in the manufacturing sector. In particular, based on predictive approach and facilitated by the nowadays growing capabilities of hardware, cloud-based solutions, and new learning approaches, maintenance can be scheduled—over cell engagement and resource monitoring—when required, for minimizing (or managing) unexpected equipment failures, improving uptime through less aggressive maintenance schedules, shortening unplanned downtime, reducing excess (direct and indirect) cost, reducing long-term damage to machines and processes, and improve safety plans. With access to increased levels of data (and over learning mechanisms), companies have the capability to conduct statistical tests using machine learning algorithms, in order to uncover root causes of problems previously unknown. This study analyses the maturity level and contributions of machine learning methods for predictive maintenance. An upward trend in publications for predictive maintenance using machine learning techniques was identified with the USA and China leading. A mapping study—steady set until early 2019 data—was employed as a formal and well-structured method to synthesize material and to report on pervasive areas of research. Type of equipment, sensors, and data are mapped to properly assist new researchers in positioning new research activities in the domain of smart maintenance. Hence, in this paper, we focus on data-driven methods for predictive maintenance (PdM) with a comprehensive survey on applications and methods until, for the sake of commenting on stable proposal, 2019 (early included). An equal repartition between evaluation and validation studies was identified, this being a symptom of an immature but growing research area. In addition, the type of contribution is mainly in the form of models and methodologies. Vibrational signal was marked as the most used data set for diagnosis in manufacturing machinery monitoring; furthermore, supervised learning is reported as the most used predictive approach (ensemble learning is growing fast). Neural networks, followed by random forests and support vector machines, were identified as the most applied methods encompassing 40% of publications, of which 67% related to deep neural network with long short-term memory predominance. Notwithstanding, there is no robust approach (no one reported optimal performance over different case tests) that works best for every problem. We finally conclude the research in this area is moving fast to gather a separate focused analysis over the last two years (whenever stable implementations will appear).
3D Finite Element Analysis of Rotary Instruments in Root Canal Dentine with Different Elastic Moduli
Authors: Prati Carlo , Tribst João Paulo Mendes , Dal Piva Amanda Maria de Oliveira , Borges Alexandre Luiz Souto , Ventre Maurizio , Zamparini Fausto , Ausiello Pietro
Published: March 2021

The aim of the present investigation was to calculate the stress distribution generated in the root dentine canal during mechanical rotation of five different NiTi endodontic instruments by means of a finite element analysis (FEA). Two conventional alloy NiTi instruments F360 25/04 and F6 Skytaper 25/06, in comparison to three heat treated alloys NiTI Hyflex CM 25/04, Protaper Next 25/06 and One Curve 25/06 were considered and analyzed. The instruments’ flexibility (reaction force) and geometrical features (cross section, conicity) were previously investigated. For each instrument, dentine root canals with two different elastic moduli(18 and 42 GPa) were simulated with defined apical ratios. Ten different CAD instrument models were created and their mechanical behaviors were analyzed by a 3D-FEA. Static structural analyses were performed with a non-failure condition, since a linear elastic behavior was assumed for all components. All the instruments generated a stress area concentration in correspondence to the root canal curvature at approx. 7 mm from the apex. The maximum values were found when instruments were analyzed in the highest elastic modulus dentine canal. Strain and von Mises stress patterns showed a higher concentration in the first part of curved radius of all the instruments. Conventional Ni-Ti endodontic instruments demonstrated higher stress magnitudes, regardless of the conicity of 4% and 6%, and they showed the highest von Mises stress values in sound, as well as in mineralized dentine canals. Heat-treated endodontic instruments with higher flexibility values showed a reduced stress concentration map. Hyflex CM 25/04 displayed the lowest von Mises stress values of, respectively, 35.73 and 44.30 GPa for sound and mineralized dentine. The mechanical behavior of all rotary endodontic instruments was influenced by the different elastic moduli and by the dentine canal rigidity.
Efficient Parallel Implementation of CTR Mode of ARX-Based Block Ciphers on ARMv8 Microcontrollers
Authors: Song JinGyo , Seo Seog Chung
Published: March 2021

With the advancement of 5G mobile telecommunication, various IoT (Internet of Things) devices communicate massive amounts of data by being connected to wireless networks. Since this wireless communication is vulnerable to hackers via data leakage during communication, the transmitted data should be encrypted through block ciphers to protect the data during communication. In addition, in order to encrypt the massive amounts of data securely, it is essential to apply one of secure mode of operation. Among them, CTR (CounTeR) mode is the most widely used in industrial applications. However, these IoT devices have limited resources of computing and memory compared to typical computers, so that it is challenging to process cryptographic algorithms that have computation-intensive tasks in IoT devices at high speed. Thus, it is required that cryptographic algorithms are optimized in IoT devices. In other words, optimizing cryptographic operations on these IoT devices is not only basic but also an essential effort in order to build secure IoT-based service systems. For efficient encryption on IoT devices, even though several ARX (Add-Rotate-XOR)-based ciphers have been proposed, it still necessary to improve the performance of encryption for smooth and secure IoT services. In this article, we propose the first parallel implementations of CTR mode of ARX-based ciphers: LEA (Lightweight Encryption Algorithm), HIGHT (high security and light weight), and revised CHAM on the ARMv8 platform, a popular microcontroller in various IoT applications. For the parallel implementation, we propose an efficient data parallelism technique and register scheduling, which maximizes the usage of vector registers. Through proposed techniques, we process the maximum amount of encryption simultaneously by utilizing all vector registers. Namely, in the case of HIGHT and revised CHAM-64/128 (resp. LEA, revised CHAM-128/128, and CHAM-128/256), we can execute 48 (resp. 24) encryptions simultaneously. In addition, we optimize the process of CTR mode by pre-computing and using the intermediate value of some initial rounds by utilizing the property that the nonce part of CTR mode input is fixed during encryptions. Through the pre-computation table, CTR mode is optimized up until round 4 in LEA, round 5 in HIGHT, and round 7 in revised CHAM. With the proposed parallel processing technique, our software provides 3.09%, 5.26%, and 9.52% of improved performance in LEA, HIGHT, and revised CHAM-64/128, respectively, compared to the existing parallel works in ARM-based MCU. Furthermore, with the proposed CTR mode optimization technique, our software provides the most improved performance with 8.76%, 8.62%, and 15.87% in LEA-CTR, HIGHT-CTR, and revised CHAM-CTR, respectively. This work is the fastest implementation of CTR mode on ARMv8 architecture to the best of our knowledge.
3D Printed Clamps for In Vitro Tensile Tests of Human Gracilis and the Superficial Third of Quadriceps Tendons
Authors: Grgić Ivan , Wertheimer Vjekoslav , Karakašić Mirko , Ivandić Željko
Published: March 2021

Recent soft tissue studies have reported issues that occur during experimentation, such as the tissue slipping and rupturing during tensile loads, the lack of standard testing procedure and equipment, the necessity for existing laboratory equipment adaptation, etc. To overcome such issues and fulfil the need for the determination of the biomechanical properties of the human gracilis and the superficial third of the quadriceps tendons, 3D printed clamps with metric thread profile-based geometry were developed. The clamps’ geometry consists of a truncated pyramid pattern, which prevents the tendons from slipping and rupturing. The use of the thread application in the design of the clamp could be used in standard clamping development procedures, unlike in previously custom-made clamps. Fused deposition modeling (FDM) was used as a 3D printing technique, together with polylactic acid (PLA), which was used as a material for clamp printing. The design was confirmed and the experiments were conducted by using porcine and human tendons. The findings justify the usage of 3D printing technology for parts manufacturing in the case of tissue testing and establish independence from the existing machine clamp system, since it was possible to print clamps for each prepared specimen and thus reduce the time for experiment setup.
Diet-Induced Obesity Promotes the Upregulation of Fas Expression on T-cells
Authors: Nyambuya Tawanda Maurice , Dludla Phiwayinkosi Vusi , Nkambule Bongani Brian
Published: March 2021

This study was conducted to assess the expression of Fas (CD95) and programmed cell death-1 (PD-1) on circulating T-cells in obesity using a diet-induced obesity mouse model. Furthermore, we aimed to determine if there are any associations between metabolic disorders and the expression of T-cell regulatory markers. A total of 12 male C57BL/6 mice were randomized into either a high-fat diet (HFD) or low-fat diet (LFD) group for 8 weeks (n = 6/group). Changes in body weights were monitored on a weekly basis. The lipid, glucose, and hematological profiles, as well as Fas and PD1 expression on the T-cell immunophenotype, were measured after 8 weeks of feeding. The HFD-fed group had a higher percentage weight gain (29.17%) in comparison with the LFD-fed group (21.74%) after the 8-week period. In addition, the HFD group had increased fasting glucose and glucose excursion following a 2-h postprandial period. The levels of total cholesterol were elevated in the HFD group when compared with the LFD group (p < 0.05). Notably, the absolute white cell count (p = 0.0096), neutrophil count (p = 0.0022, lymphocytes (p = 0.0155), and monocyte count (p = 0.0015) were elevated in the HFD group when compared with the LFD-fed group. However, the platelets (0.0680), red cell counts (0.3575), and their indices (p > 0.05) were comparable between the two groups. Interestingly, HFD feeding was associated with elevated expression of Fas on T-cells (p < 0.0001), which positively correlated with body weights (r = 0.93, p = 0.0333). No associations were found between Fas expression and dyslipidemia or fasting blood glucose levels (p > 0.05). The multivariant regression analysis showed that the association between the levels of Fas on T-cells and body weights (coefficient: −1.00, t-value: 19.27, p = 0.0330) was independent of fasting blood glucose, total cholesterol, and lymphocyte count. Lastly, the expression of PD-1 on T-cells was comparable between the two diet groups (p = 0.1822). In all, immune activation, dyslipidemia, and poor glucose control in the early stages of obesity may drive the pathogenesis of metabolic T-cell disorders. Importantly, T-cell dysfunction in obesity is partially mediated by an upregulation of Fas which is independent of dyslipidemia and hyperglycemia.
Histamine, Metabolic Remodelling and Angiogenesis: A Systems Level Approach
Authors: Moya-García Aurelio A. , Pino-Ángeles Almudena , Sánchez-Jiménez Francisca , Urdiales José Luis , Medina Miguel Ángel
Published: March 2021

Histamine is a highly pleiotropic biogenic amine involved in key physiological processes including neurotransmission, immune response, nutrition, and cell growth and differentiation. Its effects, sometimes contradictory, are mediated by at least four different G-protein coupled receptors, which expression and signalling pathways are tissue-specific. Histamine metabolism conforms a very complex network that connect many metabolic processes important for homeostasis, including nitrogen and energy metabolism. This review brings together and analyses the current information on the relationships of the “histamine system” with other important metabolic modules in human physiology, aiming to bridge current information gaps. In this regard, the molecular characterization of the role of histamine in the modulation of angiogenesis-mediated processes, such as cancer, makes a promising research field for future biomedical advances.
Pharmacological and Genetic Evidence of Dopamine Receptor 3-Mediated Vasoconstriction in Isolated Mouse Aorta
Authors: Zingales Veronica , Torrisi Sebastiano Alfio , Leggio Gian Marco , Bucolo Claudio , Drago Filippo , Salomone Salvatore
Published: March 2021

Dopamine receptors (DRs) are generally considered as mediators of vasomotor functions. However, when used in pharmacological studies, dopamine and/or DR agonists may not discriminate among different DR subtypes and may even stimulate alpha1 and beta-adrenoceptors. Here, we tested the hypothesis that D2R and/or D3R may specifically induce vasoconstriction in isolated mouse aorta. Aorta, isolated from wild-type (WT) and D3R−/− mice, was mounted in a wire myograph and challenged with cumulative concentrations of phenylephrine (PE), acetylcholine (ACh), and the D3R agonist 7-hydrxy-N,N-dipropyl-2-aminotetralin (7-OH-DPAT), with or without the D2R antagonist L741,626 and the D3R antagonist SB-277011-A. The vasoconstriction to PE and the vasodilatation to ACh were not different in WT and D3R−/−; in contrast, the contractile responses to 7-OH-DPAT were significantly weaker in D3R−/−, though not abolished. L741,626 did not change the contractile response induced by 7-OH-DPAT in WT or in D3R−/−, whereas SB-277011-A significantly reduced it in WT but did not in D3R−/−. D3R mRNA (assessed by qPCR) was about 5-fold more abundant than D2R mRNA in aorta from WT and undetectable in aorta from D3R−/−. Following transduction with lentivirus (72-h incubation) delivering synthetic microRNAs to specifically inactivate D2R (LV-miR-D2) or D3R (LV-miR-D3), the contractile response to 7-OH-DPAT was unaffected by LV-miR-D2, while it was significantly reduced by LV-miR-D3. These data indicate that, at least in mouse aorta, D3R stimulation induces vasoconstriction, while D2R stimulation does not. This is consistent with the higher expression level of D3R. The residual vasoconstriction elicited by high concentration D3R agonist in D3R−/− and/or in the presence of D3R antagonist is likely to be unrelated to DRs.
Potential Effect of Pseudevernia furfuracea (L.) Zopf Extract and Metabolite Physodic Acid on Tumour Microenvironment Modulation in MCF-10A Cells
Authors: Petrova Klaudia , Kello Martin , Kuruc Tomas , Backorova Miriam , Petrovova Eva , Vilkova Maria , Goga Michal , Rucova Dajana , Backor Martin , Mojzis Jan
Published: March 2021

Lichens comprise a number of unique secondary metabolites with remarkable biological activities and have become an interesting research topic for cancer therapy. However, only a few of these metabolites have been assessed for their effectiveness against various in vitro models. Therefore, the aim of the present study was to assess the effect of extract Pseudevernia furfuracea (L.) Zopf (PSE) and its metabolite physodic acid (Phy) on tumour microenvironment (TME) modulation, focusing on epithelial–mesenchymal transition (EMT), cancer-associated fibroblasts (CAFs) transformation and angiogenesis. Here, we demonstrate, by using flow cytometry, Western blot and immunofluorescence microscopy, that tested compounds inhibited the EMT process in MCF-10A breast cells through decreasing the level of different mesenchymal markers in a time- and dose-dependent manner. By the same mechanisms, PSE and Phy suppressed the function of Transforming growth factor beta (TGF-β)-stimulated fibroblasts. Moreover, PSE and Phy resulted in a decreasing level of the TGF-β canonical pathway Smad2/3, which is essential for tumour growth. Furthermore, PSE and Phy inhibited angiogenesis ex ovo in a quail embryo chorioallantoic model, which indicates their potential anti-angiogenic activity. These results also provided the first evidence of the modulation of TME by these substances.
Beneficial Impacts of Incorporating the Non-Natural Amino Acid Azulenyl-Alanine into the Trp-Rich Antimicrobial Peptide buCATHL4B
Authors: D’Souza Areetha R. , Necelis Matthew R. , Kulesha Alona , Caputo Gregory A. , Makhlynets Olga V.
Published: March 2021

Antimicrobial peptides (AMPs) present a promising scaffold for the development of potent antimicrobial agents. Substitution of tryptophan by non-natural amino acid Azulenyl-Alanine (AzAla) would allow studying the mechanism of action of AMPs by using unique properties of this amino acid, such as ability to be excited separately from tryptophan in a multi-Trp AMPs and environmental insensitivity. In this work, we investigate the effect of Trp→AzAla substitution in antimicrobial peptide buCATHL4B (contains three Trp side chains). We found that antimicrobial and bactericidal activity of the original peptide was preserved, while cytocompatibility with human cells and proteolytic stability was improved. We envision that AzAla will find applications as a tool for studies of the mechanism of action of AMPs. In addition, incorporation of this non-natural amino acid into AMP sequences could enhance their application properties.
Brain Metabolic Correlates of Persistent Olfactory Dysfunction after SARS-Cov2 Infection
Authors: Donegani Maria Isabella , Miceli Alberto , Pardini Matteo , Bauckneht Matteo , Chiola Silvia , Pennone Michele , Marini Cecilia , Massa Federico , Raffa Stefano , Ferrarazzo Giulia , Arnaldi Dario , Sambuceti Gianmario , Nobili Flavio , Morbelli Silvia
Published: March 2021

We aimed to evaluate the brain hypometabolic signature of persistent isolated olfactory dysfunction after SARS-CoV-2 infection. Twenty-two patients underwent whole-body [18F]-FDG PET, including a dedicated brain acquisition at our institution between May and December 2020 following their recovery after SARS-Cov2 infection. Fourteen of these patients presented isolated persistent hyposmia (smell diskettes olfaction test was used). A voxel-wise analysis (using Statistical Parametric Mapping software version 8 (SPM8)) was performed to identify brain regions of relative hypometabolism in patients with hyposmia with respect to controls. Structural connectivity of these regions was assessed (BCB toolkit). Relative hypometabolism was demonstrated in bilateral parahippocampal and fusiform gyri and in left insula in patients with respect to controls. Structural connectivity maps highlighted the involvement of bilateral longitudinal fasciculi. This study provides evidence of cortical hypometabolism in patients with isolated persistent hyposmia after SARS-Cov2 infection. [18F]-FDG PET may play a role in the identification of long-term brain functional sequelae of COVID-19.
Integrin α2β1 Represents a Prognostic and Predictive Biomarker in Primary Ovarian Cancer
Authors: Dötzer Katharina , Schlüter Friederike , Koch Franz Edler von , Brambs Christine E. , Anthuber Sabine , Frangini Sergio , Czogalla Bastian , Burges Alexander , Werner Jens , Mahner Sven , Mayer Barbara
Published: March 2021

Currently, the same first-line chemotherapy is administered to almost all patients suffering from primary ovarian cancer. The high recurrence rate emphasizes the need for precise drug treatment in primary ovarian cancer. Being crucial in ovarian cancer progression and chemotherapeutic resistance, integrins became promising therapeutic targets. To evaluate its prognostic and predictive value, in the present study, the expression of integrin α2β1 was analyzed immunohistochemically and correlated with the survival data and other therapy-relevant biomarkers. The significant correlation of a high α2β1-expression with the estrogen receptor alpha (ERα; p = 0.035) and epithelial growth factor receptor (EGFR; p = 0.027) was observed. In addition, high α2β1-expression was significantly associated with a low number of tumor-infiltrating immune cells (CD3 intratumoral, p = 0.017; CD3 stromal, p = 0.035; PD-1 intratumoral, p = 0.002; PD-1 stromal, p = 0.049) and the lack of PD-L1 expression (p = 0.005). In Kaplan–Meier survival analysis, patients with a high expression of integrin α2β1 revealed a significant shorter progression-free survival (PFS, p = 0.035) and platinum-free interval (PFI, p = 0.034). In the multivariate Cox regression analysis, integrin α2β1 was confirmed as an independent prognostic factor for both PFS (p = 0.021) and PFI (p = 0.020). Dual expression of integrin α2β1 and the hepatocyte growth factor receptor (HGFR; PFS/PFI, p = 0.004) and CD44v6 (PFS, p = 0.000; PFI, p = 0.001; overall survival [OS], p = 0.025) impaired survival. Integrin α2β1 was established as a prognostic and predictive marker in primary ovarian cancer with the potential to stratify patients for chemotherapy and immunotherapy, and to design new targeted treatment strategies.
Pancreatic Cancer Meets Human Microbiota: Close Encounters of the Third Kind
Authors: Arsenijevic Tatjana , Nicolle Remy , Bouchart Christelle , D’Haene Nicky , Demetter Pieter , Puleo Francesco , Van Laethem Jean-Luc
Published: March 2021

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal types of cancer with a dismal prognosis. The five-year survival rate has not changed significantly in over 40 years. Current first-line treatments only offer a modest increase in overall survival in unselected populations, and there is an urgent need to personalize treatment in this aggressive disease and develop new therapeutic strategies. Evolving evidence suggests that the human microbiome impacts cancerogenesis and cancer resistance to therapy. The mechanism of action and interaction of microbiome and PDAC is still under investigation. Direct and indirect effects have been proposed, and the use of several microbiome signatures as predictive and prognostic biomarkers for pancreatic cancer are opening new therapeutic horizons. In this review, we provide an overview for the clinicians of studies describing the influence and associations of oral, gastrointestinal and intratumoral microbiota on PDAC development, progression and resistance to therapy and the potential use of microbiota as a diagnostic, prognostic and predictive biomarker for PDAC.
Cost-Effectiveness of Digital Breast Tomosynthesis vs. Abbreviated Breast MRI for Screening Women with Intermediate Risk of Breast Cancer—How Low-Cost Must MRI Be?
Authors: Tollens Fabian , Baltzer Pascal A.T. , Dietzel Matthias , Rübenthaler Johannes , Froelich Matthias F. , Kaiser Clemens G.
Published: March 2021

Background: Digital breast tomosynthesis (DBT) and abbreviated breast MRI (AB-MRI) offer superior diagnostic performance compared to conventional mammography in screening women with intermediate risk of breast cancer due to dense breast tissue. The aim of this model-based economic evaluation was to analyze whether AB-MRI is cost-effective in this cohort compared to DBT. Methods: Decision analysis and Markov simulations were used to model the cumulative costs and quality-adjusted life-years (QALYs) over a time horizon of 30 years. Model input parameters were adopted from recent literature. Deterministic and probabilistic sensitivity analyses were applied to test the stability of the model. Results: In the base-case scenario, the costs of an AB-MRI examination were defined to equal the costs of a full protocol acquisition. Two-yearly screening of women with dense breasts resulted in cumulative discounted costs of $8798 and $9505 for DBT and AB-MRI, and cumulative discounted effects of 19.23 and 19.27 QALYs, respectively, with an incremental cost-effectiveness ratio of $20,807 per QALY gained in the base-case scenario. By reducing the cost of an AB-MRI examination below a threshold of $241 in sensitivity analyses, AB-MRI would become cost-saving compared to DBT. Conclusion: In comparison to DBT, AB-MRI can be considered cost-effective up to a price per examination of $593 in screening patients at intermediate risk of breast cancer.
The Tumor Suppressor MTUS1/ATIP1 Modulates Tumor Promotion in Glioma: Association with Epigenetics and DNA Repair
Authors: Ranjan Nikhil , Pandey Vimal , Panigrahi Manas Kumar , Klumpp Lukas , Naumann Ulrike , Babu Phanithi Prakash
Published: March 2021

Glioblastoma (GBM) is a highly aggressive brain tumor. Resistance mechanisms in GBM present an array of challenges to understand its biology and to develop novel therapeutic strategies. We investigated the role of a TSG, MTUS1/ATIP1 in glioma. Glioma specimen, cells and low passage GBM sphere cultures (GSC) were analyzed for MTUS1/ATIP1 expression at the RNA and protein level. Methylation analyses were done by bisulfite sequencing (BSS). The consequence of chemotherapy and irradiation on ATIP1 expression and the influence of different cellular ATIP1 levels on survival was examined in vitro and in vivo. MTUS1/ATIP1 was downregulated in high-grade glioma (HGG), GSC and GBM cells and hypermethylation at the ATIP1 promoter region seems to be at least partially responsible for this downregulation. ATIP1 overexpression significantly reduced glioma progression by mitigating cell motility, proliferation and facilitate cell death. In glioma-bearing mice, elevated MTUS1/ATIP1 expression prolonged their survival. Chemotherapy, as well as irradiation, recovered ATIP1 expression both in vitro and in vivo. Surprisingly, ATIP1 overexpression increased irradiation-induced DNA-damage repair, resulting in radio-resistance. Our findings indicate that MTUS1/ATIP1 serves as TSG-regulating gliomagenesis, progression and therapy resistance. In HGG, higher MTUS1/ATIP1 expression might interfere with tumor irradiation therapy.
Neuroendocrine Carcinomas with Atypical Proliferation Index and Clinical Behavior: A Systematic Review
Authors: Feola Tiziana , Centello Roberta , Sesti Franz , Puliani Giulia , Verrico Monica , Di Vito Valentina , Di Gioia Cira , Bagni Oreste , Lenzi Andrea , Isidori Andrea M. , Giannetta Elisa , Faggiano Antongiulio
Published: March 2021

Background: Highly proliferative (G3) neuroendocrine neoplasms are divided into well differentiated tumors (NETs) and poorly differentiated carcinomas (NECs), based on the morphological appearance. This systematic review aims to evaluate the clinicopathological features and the treatment response of the NEC subgroup with a Ki67 labeling index (LI) < 55%. Methods: A literature search was performed using MEDLINE, Cochrane Library, and Scopus between December 2019 and April 2020, last update in October 2020. We included studies reporting data on the clinicopathological characteristics, survival, and/or therapy efficacy of patients with NECs, in which the Ki67 LI was specified. Results: 8 papers were included, on a total of 268 NEC affected patients. NECs with a Ki67 LI < 55% have been reported in patients of both sexes, mainly of sixth decade, pancreatic origin, and large-cell morphology. The prevalent treatment choice was chemotherapy, followed by surgery and, in only one study, peptide receptor radionuclide therapy. The subgroup of patients with NEC with a Ki67 LI < 55% showed longer overall survival and progression free survival and higher response rates than the subgroup of patients with a tumor with higher Ki67 LI (≥55%). Conclusions: NECs are heterogeneous tumors. The subgroup with a Ki67 LI < 55% has a better prognosis and should be treated and monitored differently from NECs with a Ki67 LI ≥ 55%.
Breast Tumor Characterization Using [18F]FDG-PET/CT Imaging Combined with Data Preprocessing and Radiomics
Authors: Krajnc Denis , Papp Laszlo , Nakuz Thomas S. , Magometschnigg Heinrich F. , Grahovac Marko , Spielvogel Clemens P. , Ecsedi Boglarka , Bago-Horvath Zsuzsanna , Haug Alexander , Karanikas Georgios , Beyer Thomas , Hacker Marcus , Helbich Thomas H. , Pinker Katja
Published: March 2021

Background: This study investigated the performance of ensemble learning holomic models for the detection of breast cancer, receptor status, proliferation rate, and molecular subtypes from [18F]FDG-PET/CT images with and without incorporating data pre-processing algorithms. Additionally, machine learning (ML) models were compared with conventional data analysis using standard uptake value lesion classification. Methods: A cohort of 170 patients with 173 breast cancer tumors (132 malignant, 38 benign) was examined with [18F]FDG-PET/CT. Breast tumors were segmented and radiomic features were extracted following the imaging biomarker standardization initiative (IBSI) guidelines combined with optimized feature extraction. Ensemble learning including five supervised ML algorithms was utilized in a 100-fold Monte Carlo (MC) cross-validation scheme. Data pre-processing methods were incorporated prior to machine learning, including outlier and borderline noisy sample detection, feature selection, and class imbalance correction. Feature importance in each model was assessed by calculating feature occurrence by the R-squared method across MC folds. Results: Cross validation demonstrated high performance of the cancer detection model (80% sensitivity, 78% specificity, 80% accuracy, 0.81 area under the curve (AUC)), and of the triple negative tumor identification model (85% sensitivity, 78% specificity, 82% accuracy, 0.82 AUC). The individual receptor status and luminal A/B subtype models yielded low performance (0.46–0.68 AUC). SUVmax model yielded 0.76 AUC in cancer detection and 0.70 AUC in predicting triple negative subtype. Conclusions: Predictive models based on [18F]FDG-PET/CT images in combination with advanced data pre-processing steps aid in breast cancer diagnosis and in ML-based prediction of the aggressive triple negative breast cancer subtype.
Electrochemotherapy in Mucosal Cancer of the Head and Neck: A Systematic Review
Authors: Strojan Primož , Grošelj Aleš , Serša Gregor , Plaschke Christina Caroline , Vermorken Jan B. , Nuyts Sandra , de Bree Remco , Eisbruch Avraham , Mendenhall William M. , Smee Robert , Ferlito Alfio
Published: March 2021

Electrochemotherapy (ECT) is a local ablative treatment that is based on the reversible electroporation and intracellular accumulation of hydrophilic drug molecules, which greatly increases their cytotoxicity. In mucosal head and neck cancer (HNC), experience with ECT is limited due to the poor accessibility of tumors. In order to review the experience with ECT in mucosal HNC, we undertook a systematic review of the literature. In 22 articles, published between 1998 and 2020, 16 studies with 164 patients were described. Curative and palliative intent treatment were given to 36 (22%) and 128 patients (78%), respectively. The majority of tumors were squamous cell carcinomas (79.3%) and located in the oral cavity (62.8%). In the curative intent group, complete response after one ECT treatment was achieved in 80.5% of the patients, and in the palliative intent group, the objective (complete and partial) response rate was 73.1% (31.2% and 41.9%). No serious adverse events were reported during or soon after ECT and late effects were rare (19 events in 17 patients). The quality-of-life assessments did not show a significant deterioration at 12 months post-ECT. Provided these preliminary data are confirmed in randomized controlled trials, ECT may be an interesting treatment option in selected patients with HNC not amenable to standard local treatment.
Metabolic Reprogramming by Reduced Calorie Intake or Pharmacological Caloric Restriction Mimetics for Improved Cancer Immunotherapy
Authors: Eriau Erwan , Paillet Juliette , Kroemer Guido , Pol Jonathan G.
Published: March 2021

Caloric restriction and fasting have been known for a long time for their health- and life-span promoting effects, with coherent observations in multiple model organisms as well as epidemiological and clinical studies. This holds particularly true for cancer. The health-promoting effects of caloric restriction and fasting are mediated at least partly through their cellular effects—chiefly autophagy induction—rather than reduced calorie intake per se. Interestingly, caloric restriction has a differential impact on cancer and healthy cells, due to the atypical metabolic profile of malignant tumors. Caloric restriction mimetics are non-toxic compounds able to mimic the biochemical and physiological effects of caloric restriction including autophagy induction. Caloric restriction and its mimetics induce autophagy to improve the efficacy of some cancer treatments that induce immunogenic cell death (ICD), a type of cellular demise that eventually elicits adaptive antitumor immunity. Caloric restriction and its mimetics also enhance the therapeutic efficacy of chemo-immunotherapies combining ICD-inducing agents with immune checkpoint inhibitors targeting PD-1. Collectively, preclinical data encourage the application of caloric restriction and its mimetics as an adjuvant to immunotherapies. This recommendation is subject to confirmation in additional experimental settings and in clinical trials. In this work, we review the preclinical and clinical evidence in favor of such therapeutic interventions before listing ongoing clinical trials that will shed some light on this subject.
The Prognostic Value of Methylation Signatures and NF2 Mutations in Atypical Meningiomas
Authors: Meta Rahmina , Boldt Henning B. , Kristensen Bjarne W. , Sahm Felix , Sjursen Wenche , Torp Sverre H.
Published: March 2021

Background: Due to the solely subjective histopathological assessment, the WHO 2016 classification of human meningiomas is subject to interobserver variation. Consequently, the need for more reliable and objective markers are highly needed. The aim of this pilot study was to apply genome-wide DNA methylation analysis on a series of atypical meningiomas to evaluate the practical utility of this approach, examine whether prognostic subclasses are achieved and investigate whether there is an association between the methylation subclasses with poor prognosis and time to recurrence. NF1/2 mutation analyses were also performed to explore the prognostic value of such mutations in these atypical meningiomas. Methods: Twenty intracranial WHO grade II atypical meningiomas from adult patients were included. They consisted of 10 cases with recurrence (group I), and 10 cases without recurrence (group II). The formalin-fixed and paraffin-embedded tissues underwent standardized genome-wide DNA methylation analysis, and the profiles were matched with the reference library and tumor classifier from Heidelberg. NF1/2 somatic mutation analyses were performed using the CNSv1panel from Düsseldorf. Results: Eighteen out of 20 cases matched to the meningioma class using the common brain tumor classifier (v11b4). Four of these cases matched to a methylation subclass related to a prognostic subgroup based on a cut-off of 0.9. NF2 mutations were detected in 55% of cases across both groups, and the most prominent copy number alterations were chromosomal losses of 22q, 1p and 14q. No significant NF1 mutations were identified. Conclusions: Genome-wide DNA methylation profiling represents a useful tool in the diagnostics of meningiomas, however, methodological adjustments need to be addressed.
Genomic Instability Profiles at the Single Cell Level in Mouse Colorectal Cancers of Defined Genotypes
Authors: Dionellis Vasilis S. , Norkin Maxim , Karamichali Angeliki , Rossetti Giacomo G. , Huelsken Joerg , Ordonez-Moran Paloma , Halazonetis Thanos D.
Published: March 2021

The genomes of many human CRCs have been sequenced, revealing a large number of genetic alterations. However, the molecular mechanisms underlying the accumulation of these alterations are still being debated. In this study, we examined colorectal tumours that developed in mice with Apclox/lox, LSL-KrasG12D, and Tp53lox/lox targetable alleles. Organoids were derived from single cells and the spectrum of mutations was determined by exome sequencing. The number of single nucleotide substitutions (SNSs) correlated with the age of the tumour, but was unaffected by the number of targeted cancer-driver genes. Thus, tumours that expressed mutant Apc, Kras, and Tp53 alleles had as many SNSs as tumours that expressed only mutant Apc. In contrast, the presence of large-scale (>10 Mb) copy number alterations (CNAs) correlated strongly with Tp53 inactivation. Comparison of the SNSs and CNAs present in organoids derived from the same tumour revealed intratumoural heterogeneity consistent with genomic lesions accumulating at significantly higher rates in tumour cells compared to normal cells. The rate of acquisition of SNSs increased from the early stages of cancer development, whereas large-scale CNAs accumulated later, after Tp53 inactivation. Thus, a significant fraction of the genomic instability present in cancer cells cannot be explained by aging processes occurring in normal cells before oncogenic transformation.
Catalyst-Mediated Enhancement of Carbon Nanotube Textiles by Laser Irradiation: Nanoparticle Sweating and Bundle Alignment
Authors: Gspann Thurid S. , Kaniyoor Adarsh , Tan Wei , Kloza Philipp A. , Bulmer John S. , Mizen Jennifer , Divitini Giorgio , Terrones Jeronimo , Tune Daniel , Cook John D. , Smail Fiona R. , Elliott James A.
Published: March 2021

The photonic post-processing of suspended carbon nanotube (CNT) ribbons made by floating catalyst chemical vapor deposition (FC-CVD) results in selective sorting of the carbon nanotubes present. Defective, thermally non-conductive or unconnected CNTs are burned away, in some cases leaving behind a highly crystalline (as indicated by the Raman G:D ratio), highly conductive network. However, the improvement in crystallinity does not always occur but is dependent on sample composition. Here, we report on fundamental features, which are observed for all samples. Pulse irradiation (not only by laser but also white light camera flashes, as well as thermal processes such as Joule heating) lead to (1) the sweating-out of catalyst nanoparticles resulting in molten catalyst beads of up to several hundreds of nanometres in diameter on the textile surface and (2) a significant improvement in CNT bundle alignment. The behavior of the catalyst beads is material dependent. Here, we show the underlying mechanisms of the photonic post-treatment by modelling the macro- and microstructural changes of the CNT network and show that it is mainly the amount of residual catalyst which determines how much energy these materials can withstand before their complete decomposition.
Palladium-Incorporated α-MoC Mesoporous Composites for Enhanced Direct Hydrodeoxygenation of Anisole
Authors: Yang Yue , Liu Xiaochen , Xu Yuanjie , Gao Xing , Dai Yihu , Tang Yu
Published: March 2021

Hydrodeoxygenation (HDO) is one of the promising catalytic routes for converting biomass derived molecules to high value products. A key step of HDO is the cleavage of an aromatic C–O bond to accomplish the deoxygenation step, however, which is energetically unfavorable. Herein, we report a series of palladium (Pd)-incorporated α-phase of molybdenum carbide (α-MoC) mesoporous composites for enhanced HDO activity of a biomass model molecule, anisole. The catalysts, x%Pd/α-MoC (x% is the molar ratio of Pd/Mo), were investigated by X-ray diffraction (XRD), temperature programmed reduction (TPR), temperature programmed desorption (TPD), Brunauer–Emmett–Teller (BET), Raman, transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS) techniques. Pd is highly dispersed on α-MoC when x% ≤ 1%, but aggregate to form nanoparticles when x% = 5%. The x%Pd/α-MoC catalysts (x% ≤ 1%) show enhanced HDO activity in terms of turnover frequency (TOF) and apparent activation energy barrier (Ea) compared with α-MoC and β-Mo2C catalysts. The TOF of 1%Pd/α-MoC catalyst at 160 °C is 0.115 h−1 and the Ea is 48.2 kJ/mol. Moreover, the direct cleavage of aromatic C–O bond is preferred on 1%Pd/α-MoC catalyst. The enhanced HDO activity is attributed to superior H2 dissociation ability by the highly dispersed Pd sites on carbide. This work brings new insights for rational design of the catalyst for selective C–O bond activation.
Enhancement of Iron-Based Photo-Driven Processes by the Presence of Catechol Moieties
Authors: Moreno-Andrés Javier , Vallés Iván , García-Negueroles Paula , Santos-Juanes Lucas , Arques Antonio
Published: March 2021

Photo-induced Advanced Oxidation Processes (AOPs) using H2O2 or S2O82− as radical precursors were assessed for the abatement of six different contaminants of emerging concern (CECs). In order to increase the efficiency of these AOPs at a wider pH range, the catechol organic functional compound was studied as a potential assistant in photo-driven iron-based processes. Different salinity regimes were also studied (in terms of Cl− concentration), namely low salt water (1 g·L−1) or a salt–water (30 g·L−1) matrix. Results obtained revealed that the presence of catechol could efficiently assist the photo-Fenton system and partly promote the photo-induced S2O82− system, which was highly dependent on salinity. Regarding the behavior of individual CECs, the photo-Fenton reaction was able to enhance the degradation of all six CECs, meanwhile the S2O82−-based process showed a moderate enhancement for acetaminophen, amoxicillin or clofibric acid. Finally, a response-surface methodology was employed to determine the effect of pH and catechol concentration on the different photo-driven processes. Catechol was removed during the degradation process. According to the results obtained, the presence of catechol in organic macromolecules can bring some advantages in water treatment for either freshwater (wastewater) or seawater (maritime or aquaculture industry).
Integration of Spectral Reflectance Indices and Adaptive Neuro-Fuzzy Inference System for Assessing the Growth Performance and Yield of Potato under Different Drip Irrigation Regimes
Authors: Elsayed Salah , El-Hendawy Salah , Khadr Mosaad , Elsherbiny Osama , Al-Suhaibani Nasser , Dewir Yaser Hassan , Tahir Muhammad Usman , Mubushar Muhammad , Darwish Waleed
Published: March 2021

Simultaneous and timely assessment of growth and water status-related plant traits is critical for precision irrigation management in arid regions. Here, we used proximal hyperspectral sensing tools to estimate biomass fresh weight (BFW), biomass dry weight (BDW), canopy water content (CWC), and total tuber yield (TTY) of two potato varieties irrigated with 100%, 75%, and 50% of the estimated crop evapotranspiration (ETc). Plant traits were assessed remotely using published and newly constructed vegetation and water spectral reflectance indices (SRIs). We integrated genetic algorithm (GA) and adaptive neuro-fuzzy inference system (ANFIS) models to predict the measured traits based on all SRIs. The different plant traits and SRIs varied significantly (p < 0.05) between the three irrigation regimes for the two varieties. The values of plant traits and majority SRIs showed a continuous decrease from the 100% ETc to the 50% ETc. Water-SRIs performed better than vegetation-SRIs for estimating the four plant traits. Almost all indices of the two SRI types had a weak relationship with the four plant traits (R2 = 0.00–0.37) under each irrigation regime. However, the majority of vegetation-SRIs and all water-SRIs showed strong relationships with BFW, CWC, and TTY (R2 ≥ 0.65) and moderate relationships with BDW (R2 ≥ 0.40) when the data of all irrigation regimes and varieties were analyzed together for each growing season or the data of all irrigation regimes, varieties, and seasons were combined together. The ANFIS-GA model predicted plant traits with satisfactory accuracy in both calibration (R2 = 1.0) and testing (R2 = 0.72–0.97) modes. The results indicate that SRI-based ANFIS models can improve plant trait estimation. This analysis also confirmed the benefits of applying GA to ANFIS to estimate plant responses to different growth conditions.
Application of the Generalized Laplace Homotopy Perturbation Method to the Time-Fractional Black–Scholes Equations Based on the Katugampola Fractional Derivative in Caputo Type
Authors: Thanompolkrang Sirunya , Sawangtong Wannika , Sawangtong Panumart
Published: March 2021

In the finance market, the Black–Scholes equation is used to model the price change of the underlying fractal transmission system. Moreover, the fractional differential equations recently are accepted by researchers that fractional differential equations are a powerful tool in studying fractal geometry and fractal dynamics. Fractional differential equations are used in modeling the various important situations or phenomena in the real world such as fluid flow, acoustics, electromagnetic, electrochemistry and material science. There is an important question in finance: “Can the fractional differential equation be applied in the financial market?”. The answer is “Yes”. Due to the self-similar property of the fractional derivative, it can reply to the long-range dependence better than the integer-order derivative. Thus, these advantages are beneficial to manage the fractal structure in the financial market. In this article, the classical Black–Scholes equation with two assets for the European call option is modified by replacing the order of ordinary derivative with the fractional derivative order in the Caputo type Katugampola fractional derivative sense. The analytic solution of time-fractional Black–Scholes European call option pricing equation with two assets is derived by using the generalized Laplace homotopy perturbation method. The used method is the combination of the homotopy perturbation method and generalized Laplace transform. The analytic solution of the time-fractional Black–Scholes equation is carried out in the form of a Mittag–Leffler function. Finally, the effects of the fractional-order in the Caputo type Katugampola fractional derivative to change of a European call option price are shown.
Variation in Assemblages of Freshwater Mussels Downstream of Dams and Dam Removals in the Lake Michigan Basin, Michigan, USA
Authors: Barnett Shaughn E. , Woolnough Daelyn A.
Published: March 2021

Impacts of barriers, including dam removals, on aquatic diversity are poorly understood. We assessed freshwater mussel assemblages and microhabitat downstream of uncontrolled and controlled low-head dams and low-head dam removals in Michigan, USA. The objectives of this study were to quantify whether downstream mussel assemblages and microhabitat parameters differ by anthropogenic barrier and along a downstream gradient, and to determine parameters that were predictors of mussel diversity and density. Sampling consisted of standardized timed-searches and quadrat excavations. Results suggest that areas downstream of dams had higher mussel diversity than dam removals, and mussel assemblages differed along a downstream gradient for uncontrolled and controlled dams. Indicator Species Analyses determined mussel species representative of downstream river reaches from uncontrolled low-head dams and removals. Predictor variables for mussel assemblages included substrate classes and total suspended solids. Controlled dams contained the least fine substrates (%) and highest coarse substrates (%) in downstream reaches. This study suggests that rivers with uncontrolled low-head dams and removals provide downstream habitat that support viable mussel assemblages. Results from this study also suggest that evidence of mussel assemblage recovery following dam removal may take many years. Quantification of barrier-related impacts, as shown in this study, are imperative to guide conservation of aquatic fauna.