bluuebunny/crossref_metadata_2025 huggingface dataset:
One-Dimensional Convolutional Neural Networks for Hyperspectral Analysis of Nitrogen in Plant Leaves
Authors: Pourdarbani Razieh , Sabzi Sajad , Rohban Mohammad H. , Hernández-Hernández José Luis , Gallardo-Bernal Iván , Herrera-Miranda Israel , García-Mateos Ginés
Published: December 2021

Accurately determining the nutritional status of plants can prevent many diseases caused by fertilizer disorders. Leaf analysis is one of the most used methods for this purpose. However, in order to get a more accurate result, disorders must be identified before symptoms appear. Therefore, this study aims to identify leaves with excessive nitrogen using one-dimensional convolutional neural networks (1D-CNN) on a dataset of spectral data using the Keras library. Seeds of cucumber were planted in several pots and, after growing the plants, they were divided into different classes of control (without excess nitrogen), N30% (excess application of nitrogen fertilizer by 30%), N60% (60% overdose), and N90% (90% overdose). Hyperspectral data of the samples in the 400–1100 nm range were captured using a hyperspectral camera. The actual amount of nitrogen for each leaf was measured using the Kjeldahl method. Since there were statistically significant differences between the classes, an individual prediction model was designed for each class based on the 1D-CNN algorithm. The main innovation of the present research resides in the application of separate prediction models for each class, and the design of the proposed 1D-CNN regression model. The results showed that the coefficient of determination and the mean squared error for the classes N30%, N60% and N90% were 0.962, 0.0005; 0.968, 0.0003; and 0.967, 0.0007, respectively. Therefore, the proposed method can be effectively used to detect over-application of nitrogen fertilizers in plants.
A Comparison of Different Folding Models in Variations of the Map Folding Problem
Authors: Jia Yiyang , Mitani Jun
Published: December 2021

In this paper, we compare the performance of three different folding models when they are applied to three different map folding settings. Precisely, the three folding models include the simple folding model, the simple folding–unfolding model, and the general folding model. The different map folding settings are discussed by comparing different folded states, i.e., different overlapping orders on the set of the squares of 1 × n maps, the squares of m × n maps, and the squares lying on the boundary of m × n maps. These folding models are abstracts of manual works and robotics. We clarify the relationship between their reachable final folded states under different settings and give proof of all the inclusion relationships between every two of these sets. In addition, there are nine distinct problems with the three folding models applied to three folding settings. We give the optimal linear time solutions to all the unsolved ones: the valid total overlapping order problems of 1 × n maps, m × n maps, as well as the valid boundary overlapping order problems of m × n maps with the three different folding models. Our work gives the conclusion of the research field where the folding models and the overlapping orders of map folding are concerned.
Grouping Ceramic Variability with pXRF for Pottery Trade and Trends in Early Medieval Southern Tuscany. Preliminary Results from the Vetricella Case Study (Grosseto, Italy)
Authors: Fornacelli Cristina , Volpi Vanessa , Ponta Elisabetta , Russo Luisa , Briano Arianna , Donati Alessandro , Giamello Marco , Bianchi Giovanna
Published: December 2021

The characterization of archaeological ceramics according to their chemical composition provides essential information about the production and distribution of specific pottery wares. If a correlation between compositional patterns and local production centers is assumed, pottery manufacturing and trade and, more generally, economic, political, as well as cultural relations between communities and regions can be investigated. In the present paper, the combined application of portable XRF and statistical analysis to the investigation of a large repertory of ceramic fragments allowed us to group the assemblage by identifying geochemical clusters. The results from the chemical and statistical analysis were then compared with reference ceramic samples from the same area, as well as with macroscopic and petrographic observations to confirm, coalesce or sub-divide putative sub-divisions. The study of 141 samples from different sites located within a wide area spanning across the Colline Metallifere and the coast (Monterotondo Marittimo, Roccastrada, Donoratico, and Vetricella) provided new clues for a new interpretive archaeological framework that suggests that there was a well-defined organization of pottery manufacturing and circulation across southern Tuscany during the early medieval period.
Pathological Mechanisms and Additional Factors Involved in Complex Neck Traumatology
Authors: Bulgaru-Iliescu Diana , Nicolau Andrei , Roșca Ștefan , Ciureanu Ioan-Adrian , Severin Florentina
Published: December 2021

Background. Cervical trauma can be closed or open, have different degrees of severity, incidence rates, prevalence, or mortality, with variations in the presence of demographic factors. The different types of traumatic injuries have a certain pattern of occurrence depending on criteria related to sex, age, alcohol consumption, and socio-demographic factors. Increasing the rate of trauma is becoming a public health problem and it is necessary to study their epidemiology and implement control strategies. Aims. The objectives of the study are to establish the particularities of epidemiological, morphopathological, and pathophysiological factors involved in complex neck traumatology. Methods. The study group consisted of 384 patients, representative for the population of Moldova, who presented at the ENT Clinic, Hospital “St. Spiridon” Iași and the Institute of Forensic Medicine, Iași during 2012–2016, with complex cervical trauma pathology, produced by various mechanisms, such as car accidents, domestic accidents, aggressions, ballistic trauma, self-inflicted attempts, hanging or strangulation. Data were collected from autopsy reports and medical records. Results. Complex cervical trauma occurs with a predisposition in males, with an average age of 43 years, from rural areas. The mechanism of cervical trauma is predominantly self-inflicted—hanging in 78.4% of the total number of cases, followed by 14.8% of stabbing aggression. The majority of neck injuries, both open and closed, are located in anatomical zone II (73.6%), vascular and pharyngeal are produced by stabbing. Psychiatric disorders and blood alcohol levels are correlated with complex cervical trauma caused by self-inflicted mechanism—hanging and can be considered a predictive factor of suicide attempts. Conclusions. Overall, the vast majority of closed neck injuries were caused by the self-inflicted mechanism, attempted suicide by hanging, followed by the accidental mechanism. Regarding the penetrating complex aero-digestive cervical traumas, they were mostly produced by stabbing both in aggression and self-inflicted circumstances. Aggravating addictive factors such as alcoholism and mental disorders require a competent assessment in terms of the indication of institutionalized treatment, prevention of repeated self-inflicted attempts, or social reintegration.
Development of a Gaussian Process Model as a Surrogate to Study Load Bridging Performance in Racked Pallets
Authors: Molina Eduardo , Horvath Laszlo
Published: December 2021

Current pallet design methodology frequently underestimates the load capacity of the pallet by assuming the payload is uniformly distributed and flexible. By considering the effect of payload characteristics and their interactions during pallet design, the structure of pallets can be optimized and raw material consumption reduced. The objective of this study was to develop a full description of how such payload characteristics affect load bridging on unit loads of stacked corrugated boxes on warehouse racking support. To achieve this goal, the authors expanded on a previously developed finite element model of a simplified unit load segment and conducted a study to screen for the significant factors and interactions. Subsequently, a Gaussian process (GP) regression model was developed to efficiently and accurately replicate the simulation model. Using this GP model, a quantification of the effects and interactions of all the identified significant factors was provided. With this information, packaging designers and researchers can engineer unit loads that consider the effect of the relevant design variables and their impact on pallet performance. Such a model has not been previously developed and can potentially reduce packaging materials’ costs.
Fusion Visualization Technique to Improve a Three-Dimensional Isotope-Selective CT Image Based on Nuclear Resonance Fluorescence with a Gamma-CT Image
Authors: Ali Khaled , Zen Heishun , Ohgaki Hideaki , Kii Toshiteru , Hayakawa Takehito , Shizuma Toshiyuki , Katoh Masahiro , Taira Yoshitaka , Fujimoto Masaki , Toyokawa Hiroyuki
Published: December 2021

One of the most noteworthy aspects of computed tomography (CT) based on the nuclear resonance fluorescence (NRF) transmission method is the isotope selectivity that makes it possible to discern an isotope of interest from other isotopes within a sample. We experimentally obtained a three-dimensional (3D) isotope-selective CT image based on the NRF transmission method (3D NRF-CT) for the enriched lead isotope distribution of 208Pb in a cylindrical holder in a previous study. The cylindrical holder’s diameter and height are 25 mm and 20 mm, respectively. The NRF-CT imaging technique requires a considerable data accumulation time. It took 48 h to obtain an image with a resolution of 4 mm/pixel in the horizontal plane and 8 mm/pixel in the vertical plane using a laser Compton scattering (LCS) gamma-ray beam with a beam size of 2 mm and a flux density of 10 photons/s/eV. Improving the NRF-CT image resolution with the existing hardware is challenging. Therefore, we proposed an alternative method to improve the NRF-CT image resolution using the fusion visualization (FV) technique by combining the NRF-CT image including isotopic information with a gamma-CT image, which provides better pixel resolution. The 3D gamma-CT image for the same sample was measured at the same beamline BL1U in the ultraviolet synchrotron orbital radiation-III (UVSOR-III) synchrotron radiation facility at the Institute of Molecular Science at the National Institutes of Natural Sciences in Japan under similar experimental conditions except for the LCS gamma-ray beam flux and beam size. Obtaining a 3D gamma-CT image with a resolution of 1 mm/pixel took 5 h using an LCS gamma-ray beam with a beam size of 1 mm and a flux density of 0.7 photons/s/eV. The data processing of the FV technique has been developed, and the 3D NRF-CT image quality was improved.
Using Brain-Computer Interface to Control a Virtual Drone Using Non-Invasive Motor Imagery and Machine Learning
Authors: Dumitrescu Catalin , Costea Ilona-Madalina , Semenescu Augustin
Published: December 2021

In recent years, the control of devices “by the power of the mind” has become a very controversial topic but has also been very well researched in the field of state-of-the-art gadgets, such as smartphones, laptops, tablets and even smart TVs, and also in medicine, to be used by people with disabilities for whom these technologies may be the only way to communicate with the outside world. It is well known that BCI control is a skill and can be improved through practice and training. This paper aims to improve and diversify signal processing methods for the implementation of a brain-computer interface (BCI) based on neurological phenomena recorded during motor tasks using motor imagery (MI). The aim of the research is to extract, select and classify the characteristics of electroencephalogram (EEG) signals, which are based on sensorimotor rhythms, for the implementation of BCI systems. This article investigates systems based on brain-computer interfaces, especially those that use the electroencephalogram as a method of acquisition of MI tasks. The purpose of this article is to allow users to manipulate quadcopter virtual structures (external, robotic objects) simply through brain activity, correlated with certain mental tasks using undecimal transformation (UWT) to reduce noise, Independent Component Analysis (ICA) together with determination coefficient (r2) and, for classification, a hybrid neural network consisting of Radial Basis Functions (RBF) and a multilayer perceptron–recurrent network (MLP–RNN), obtaining a classification accuracy of 95.5%. Following the tests performed, it can be stated that the use of biopotentials in human–computer interfaces is a viable method for applications in the field of BCI. The results presented show that BCI training can produce a rapid change in behavioral performance and cognitive properties. If more than one training session is used, the results may be beneficial for increasing poor cognitive performance. To achieve this goal, three steps were taken: understanding the functioning of BCI systems and the neurological phenomena involved; acquiring EEG signals based on sensorimotor rhythms recorded during MI tasks; applying and optimizing extraction methods, selecting and classifying characteristics using neuronal networks.
Effects of Dry Heat Treatment and Milling on Sorghum Chemical Composition, Functional and Molecular Characteristics
Authors: Batariuc Ana , Ungureanu-Iuga Mădălina , Mironeasa Silvia
Published: December 2021

This study aimed to highlight the effects of grains dry heat treatment, flour particle size and variety on sorghum flour nutritional, functional, and molecular characteristics. The results obtained showed that dry heat treatment led to fat, fiber and water absorption capacity increase, while the moisture, protein, ash, water retention capacity, solubility index, foaming capacity, and FT-IR absorption bands characteristic to phytic acids decreased with temperature applied raised. Particle size reduction determined lower protein, solubility index, and emulsifying activity and higher fat content, oil absorption capacity, swelling power, and foaming capacity. White sorghum flour fractions presented lower protein content, except when they were treated at 140 °C, lower carbohydrates and fibers and higher fat content compared to those made of red sorghum. Moderate significant correlations (p < 0.05) were observed between some of the functional properties and proximate composition of flours. Thus, both dry heat treatment conditions and particle size exerted significant influences of sorghum flour chemical and functional properties. These results showed the importance of particle size and dry heat treatment on sorghum flours functionality, being helpful for further optimizations and choices for bakery products use.
Characteristics of Photon Beam and Preservation of Coherence in Fourth-Generation Light Sources
Authors: Oh Bonghoon , Ko Jinjoo , Lee Jaeyu , Jang Gyeongsu , Shin Seunghwan
Published: December 2021

Fourth-generation storage rings (4GSRs) that exploit the multi-bend achromat lattice concept may be able to surpass the brightness and coherence that are attained using the present third-generation storage rings. This paper presents the characteristics of photon beams and an analysis of their coherence properties in Korea-4GSR to represent 4GSRs.
Tailored Nanoparticles as Vaccine Components
Authors: Popa Alina , Springer Sebastian
Published: December 2021

Nanoparticles are components of many vaccines, helping to make them more stable and immunogenic. They protect antigens—or the genetic material encoding them—from degradation, target them to particular tissues or cells, promote their uptake into antigen-presenting cells, and activate the immune response (in the form of adjuvants). Nanoparticles come in many different kinds, some with uniform composition and some with elaborate core-and-shell structures, including lipid membranes. The antigen is usually retained inside, and the surface can be functionalized by targeting or activating proteins and carbohydrates. This minireview provides a general introductory overview to vaccination and a survey of nanoparticles, their types, production, characteristics, and individual applications in vaccines, and finally, a brief look into the world of artificial antigen-presenting cells.
A Dual-Stage Vocabulary of Features (VoF)-Based Technique for COVID-19 Variants’ Classification
Authors: Jamil Sonain , Rahman MuhibUr
Published: December 2021

Novel coronavirus, known as COVID-19, is a very dangerous virus. Initially detected in China, it has since spread all over the world causing many deaths. There are several variants of COVID-19, which have been categorized into two major groups. These groups are variants of concern and variants of interest. Variants of concern are more dangerous, and there is a need to develop a system that can detect and classify COVID-19 and its variants without touching an infected person. In this paper, we propose a dual-stage-based deep learning framework to detect and classify COVID-19 and its variants. CT scans and chest X-ray images are used. Initially, the detection is done through a convolutional neural network, and then spatial features are extracted with deep convolutional models, while handcrafted features are extracted from several handcrafted descriptors. Both spatial and handcrafted features are combined to make a feature vector. This feature vector is called the vocabulary of features (VoF), as it contains spatial and handcrafted features. This feature vector is fed as an input to the classifier to classify different variants. The proposed model is evaluated based on accuracy, F1-score, specificity, sensitivity, specificity, Cohen’s kappa, and classification error. The experimental results show that the proposed method outperforms all the existing state-of-the-art methods.
The Recipe for Success: Repin’s Painting Barge-Haulers on the Volga and Stasov’s Conception of Russian Art
Authors: Shimshon Ariela
Published: December 2021

Barge-Haulers on the Volga is one of the most famous works of the Russian realist painter Ilya Repin. As I demonstrate in this article, on the one hand, it brought Repin resounding success and, on the other, it molded his creative conception. The Russian art critic Vladimir Stasov outlined the artist’s success. In March 1873, Stasov’s poetic depiction of Repin’s painting, where he expressed his admiration for Repin’s talent, focusing on specific aspects that he contended had to be included in a perfect work of Russian art, was published in the daily newspaper Sankt-Peterburgskie Vedomosti. I attempt to show that Stasov’s praise had a devastating effect on Repin’s creative process. By examining Repin’s post Barge-Haulers successful works for this pattern, I show how the painter tried to incorporate every one of the “ingredients” that Stasov outlined and ultimately created a typified group of paintings documenting life on the periphery of the Russian Empire with those features, which marked his entire career.
Characteristic Analysis of Dual-Polarization Weather Radar Echoes of Convective Precipitation and Snowfall in the Mount Everest Region
Authors: Wang Lei , Li Yueqing , Xu Xiangde , Li Fang
Published: December 2021

This paper introduces the X-band weather radar dual-polarization parameters of isolated convective cell precipitation and meso/microscale snowfall on Mount Everest and presents the first precipitation observations based on dual-polarization weather radar in this area. Compared with the Chengdu Plain, Mount Everest experienced convective precipitation on smaller horizontal and vertical scales with a narrower Zdr probability density spectrum (uniformly distributed around approximately 0). The Zh profile on Mount Everest displayed two peaks, unlike that over the plains, and the precipitation at the strong convective core was denser. Furthermore, during winter snowfall on the northern slope of Mount Everest, when the boundary layer exhibited sufficient water vapor and dynamic uplift, due to the low boundary layer temperature (<0 °C), water vapor produced stratiform clouds in the middle and lower layers (approximately 1.5 km above ground level (AGL)). Water vapor condensation at 1.5–2.5 km AGL led to latent heat release, which increased the temperature of regional stratiform clouds with increasing height. Consequently, the temperature at the stratiform cloud top height (2.5 km AGL) unexpectedly exceeded 0 °C. Additionally, the −20 °C isotherm was at approximately 4 km AGL, indicating that the middle- and upper-layer atmospheric temperatures remained low. Therefore, thermal instability occurred between the stratiform cloud top height and the middle/upper atmosphere, forming convective motion. These findings confirm the occurrence of elevated winter snowfall convection above Mount Everest and may have certain reference value for retrieving raindrop size distributions, quantitatively estimating precipitation, and parameterizing cloud microphysical processes in numerical prediction models for the Qinghai-Tibetan Plateau.
Contributions of Ammonia to High Concentrations of PM2.5 in an Urban Area
Authors: Park Junsu , Kim Eunhye , Oh Sangmin , Kim Haeri , Kim Soontae , Kim Yong Pyo , Song Mijung
Published: December 2021

Atmospheric ammonia (NH3) plays a critical role in PM2.5 pollution. Data on atmospheric NH3 are scanty; thus, the role of NH3 in the formation of ammonium ions (NH4+) in various environments is understudied. Herein, we measured concentrations of NH3, PM2.5, and its water-soluble SO42−, NO3−, and NH4+ ions (SNA) at an urban site in Jeonju, South Korea from May 2019 to April 2020. During the measurement period, the average concentrations of NH3 and PM2.5 were 10.5 ± 4.8 ppb and 24.0 ± 12.8 μg/m3, respectively, and SNA amounted to 4.3 ± 3.1, 4.4 ± 4.9, and 1.6 ± 1.8 μg/m3, respectively. A three-dimensional photochemical model analysis revealed that a major portion of NH3, more than 88%, originated from Korea. The enhancement of the ammonium-to-total ratio of NH3, NHX (NHR = [NH4+]/[NH4+] + [NH3]) was observed up to ~0.61 during the increase of PM2.5 concentration (PM2.5 ≥ 25 μg/m3) under low temperature and high relative humidity conditions, particularly in winter. The PM2.5 and SNA concentrations increased exponentially as NHR increased, indicating that NH3 contributed significantly to SNA formation by gas-to-particle conversion. Our study provided experimental evidence that atmospheric NH3 in the urban area significantly contributed to SNA formation through gas-to-particle conversion during PM2.5 pollution episodes.
GO-E-MON: A New Online Platform for Decentralized Cognitive Science
Authors: Yazawa Satoshi , Sakaguchi Kikue , Hiraki Kazuo
Published: December 2021

Advances in web technology and the widespread use of smartphones and PCs have proven that it is possible to optimize various services using personal data, such as location information and search history. While considerations of personal privacy and legal aspects lead to situations where data are monopolized by individual services and companies, a replication crisis has been pointed out for the data of laboratory experiments, which is challenging to solve given the difficulty of data distribution. To ensure distribution of experimental data while guaranteeing security, an online experiment platform can be a game changer. Current online experiment platforms have not yet considered improving data distribution, and it is currently difficult to use the data obtained from one experiment for other purposes. In addition, various devices such as activity meters and consumer-grade electroencephalography meters are emerging, and if a platform that collects data from such devices and tasks online is to be realized, the platform will hold a large amount of sensitive data, making it even more important to ensure security. We propose GO-E-MON, a service that combines an online experimental environment with a distributed personal data store (PDS), and explain how GO-E-MON can realize the reuse of experimental data with the subject’s consent by connecting to a distributed PDS. We report the results of the experiment in a groupwork lecture for university students to verify whether this method works. By building an online experiment environment integrated with a distributed PDS, we present the possibility of integrating multiple experiments performed by different experimenters—with the consent of individual subjects—while solving the security issues.
Spatial Sound in a 3D Virtual Environment: All Bark and No Bite?
Authors: Meghanathan Radha Nila , Ruediger-Flore Patrick , Hekele Felix , Spilski Jan , Ebert Achim , Lachmann Thomas
Published: December 2021

Although the focus of Virtual Reality (VR) lies predominantly on the visual world, acoustic components enhance the functionality of a 3D environment. To study the interaction between visual and auditory modalities in a 3D environment, we investigated the effect of auditory cues on visual searches in 3D virtual environments with both visual and auditory noise. In an experiment, we asked participants to detect visual targets in a 360° video in conditions with and without environmental noise. Auditory cues indicating the target location were either absent or one of simple stereo or binaural audio, both of which assisted sound localization. To investigate the efficacy of these cues in distracting environments, we measured participant performance using a VR headset with an eye tracker. We found that the binaural cue outperformed both stereo and no auditory cues in terms of target detection irrespective of the environmental noise. We used two eye movement measures and two physiological measures to evaluate task dynamics and mental effort. We found that the absence of a cue increased target search duration and target search path, measured as time to fixation and gaze trajectory lengths, respectively. Our physiological measures of blink rate and pupil size showed no difference between the different stadium and cue conditions. Overall, our study provides evidence for the utility of binaural audio in a realistic, noisy and virtual environment for performing a target detection task, which is a crucial part of everyday behaviour—finding someone in a crowd.
Beer and Allergens
Authors: Vriesekoop Frank
Published: December 2021

Food allergies are an important global health concern, with many countries following the World Health Organisation’s guidelines with regards to due labelling of foods and, as such, providing forewarning about the presence of potential allergens to potential consumers. While for some produce, the link to specific allergens might be very clear to most consumers, this is not the case for all produce. People with specific food-related allergies usually know what to look out for, but occasionally, unexpected allergens are present in trusted produce. Beer is known to most to contain barley, which will contain gluten-like proteins that can cause allergic reactions in some people. Similarly, beer might contain sulphites and other potential allergens traditionally associated with beers. This review aims to examine a wide range of allergens that have entered the beer production process in recent years. As a result, examples of beers that contain one or more of the 14 EU-UK listed allergens are described, different allergen regulations in different countries are emphasised and their impact explained, and a number of case studies involving allergic reactions following exposure to and the ingestion of beer are highlighted.
How Localized Z-Disc Damage Affects Force Generation and Gene Expression in Cardiomyocytes
Authors: Müller Dominik , Donath Sören , Brückner Emanuel Georg , Biswanath Devadas Santoshi , Daniel Fiene , Gentemann Lara , Zweigerdt Robert , Heisterkamp Alexander , Kalies Stefan Michael Klaus
Published: December 2021

The proper function of cardiomyocytes (CMs) is highly related to the Z-disc, which has a pivotal role in orchestrating the sarcomeric cytoskeletal function. To better understand Z-disc related cardiomyopathies, novel models of Z-disc damage have to be developed. Human pluripotent stem cell (hPSC)-derived CMs can serve as an in vitro model to better understand the sarcomeric cytoskeleton. A femtosecond laser system can be applied for localized and defined damage application within cells as single Z-discs can be removed. We have investigated the changes in force generation via traction force microscopy, and in gene expression after Z-disc manipulation in hPSC-derived CMs. We observed a significant weakening of force generation after removal of a Z-disc. However, no significant changes of the number of contractions after manipulation were detected. The stress related gene NF-kB was significantly upregulated. Additionally, α-actinin (ACTN2) and filamin-C (FLNc) were upregulated, pointing to remodeling of the Z-disc and the sarcomeric cytoskeleton. Ultimately, cardiac troponin I (TNNI3) and cardiac muscle troponin T (TNNT2) were significantly downregulated. Our results allow a better understanding of transcriptional coupling of Z-disc damage and the relation of damage to force generation and can therefore finally pave the way to novel therapies of sarcomeric disorders.
In Silico Approaches to Identify Polyphenol Compounds as α-Glucosidase and α-Amylase Inhibitors against Type-II Diabetes
Authors: Riyaphan Jirawat , Pham Dinh-Chuong , Leong Max K. , Weng Ching-Feng
Published: December 2021

Type-II diabetes mellitus (T2DM) results from a combination of genetic and lifestyle factors, and the prevalence of T2DM is increasing worldwide. Clinically, both α-glucosidase and α-amylase enzymes inhibitors can suppress peaks of postprandial glucose with surplus adverse effects, leading to efforts devoted to urgently seeking new anti-diabetes drugs from natural sources for delayed starch digestion. This review attempts to explore 10 families e.g., Bignoniaceae, Ericaceae, Dryopteridaceae, Campanulaceae, Geraniaceae, Euphorbiaceae, Rubiaceae, Acanthaceae, Rutaceae, and Moraceae as medicinal plants, and folk and herb medicines for lowering blood glucose level, or alternative anti-diabetic natural products. Many natural products have been studied in silico, in vitro, and in vivo assays to restrain hyperglycemia. In addition, natural products, and particularly polyphenols, possess diverse structures for exploring them as inhibitors of α-glucosidase and α-amylase. Interestingly, an in silico discovery approach using natural compounds via virtual screening could directly target α-glucosidase and α-amylase enzymes through Monte Carto molecular modeling. Autodock, MOE-Dock, Biovia Discovery Studio, PyMOL, and Accelrys have been used to discover new candidates as inhibitors or activators. While docking score, binding energy (Kcal/mol), the number of hydrogen bonds, or interactions with critical amino acid residues have been taken into concerning the reliability of software for validation of enzymatic analysis, in vitro cell assay and in vivo animal tests are required to obtain leads, hits, and candidates in drug discovery and development.
Characterization of SLC34A2 as a Potential Prognostic Marker of Oncological Diseases
Authors: Vlasenkova Ramilia , Nurgalieva Alsina , Akberova Natalia , Bogdanov Mikhail , Kiyamova Ramziya
Published: December 2021

The main goal of this study is to consider SLC34A2 as a potential prognostic marker of oncological diseases using the mutational, expression, and survival data of cancer studies which are publicly available online. We collected data from four databases (cBioPortal, The Cancer Genome Atlas; cBioPortal, Genie; International Cancer Genome Consortium; ArrayExpress). In total, 111,283 samples were categorized according to 27 tumor locations. Ninety-nine functionally significant missense mutations and twelve functionally significant indel mutations in SLC34A2 were found. The most frequent mutations were SLC34A2-ROS1, p.T154A, p.P506S/R/L, p.G257A/E/R, p.S318W, p.A396T, p.P410L/S/H, p.S461C, p.A473T/V, and p.Y503H/C/F. The upregulation of SLC34A2 was found in samples of myeloid, bowel, ovarian, and uterine tumors; downregulation was found in tumor samples of breast, liver, lung, and skin cancer tumors. It was found that the life expectancy of breast and thymus cancer patients with an SLC34A2 mutation is lower, and it was revealed that SLC34A2 overexpression reduced the life span of patients with brain, ovarian, and pancreatic tumors. Thereby, for these types of oncological diseases, the mutational profile of SLC34A2 can be a potential prognostic marker for breast and thymus cancers, and the upregulation of SLC34A2 can be a potential prognostic marker for brain, ovarian, and pancreatic cancers.
A Systematic Review of MicroRNA Signatures Associated with the Progression of Leukoplakia with and without Epithelial Dysplasia
Authors: Kaunein Nadia , Ramani Rishi Sanjay , Koo Kendrick , Moore Caroline , Celentano Antonio , McCullough Michael , Yap Tami
Published: December 2021

Oral cancer is a significant public health issue, being the eighth most common cancer worldwide with over 300,000 cases diagnosed annually. Early diagnosis and adequate management of oral potentially malignant disorders (OPMDs) before transformation into oral squamous cell carcinoma (OSCC) is critical to reduce deaths, morbidity, and to improve overall prognosis. MicroRNAs (miRNAs) are small noncoding RNAs involved in the post-transcriptional regulation of protein expression and implicated in the control of numerous cellular pathways and impacting physiological, developmental, and pathological processes. Dysregulation of miRNAs has been reported in many cancers and has been demonstrated to play a critical role in cancer initiation, progression, apoptosis, invasion and metastasis. This systematic review provides a comprehensive summary of the prevailing literature on miRNA signatures in OPMDs, specifically leukoplakia with or without oral epithelial dysplasia, and their utility in predicting malignant transformation into OSCC. Eighteen articles describing 73 unique and differentially expressed microRNAs met the criteria for inclusion in this review. We reviewed the characteristics and methodology for each of these studies and assessed the sensitivity and specificity of the studied miRNAs in predicting malignant transformation. This systematic review highlights the significant interest in miRNAs and their tremendous potential as prognostic markers for predicting the malignant transformation of OPMDs into OSCC.
Skin Wound Healing of the Adult Newt, Cynops pyrrhogaster: A Unique Re-Epithelialization and Scarless Model
Authors: Ishii Tatsuyuki , Takashimizu Ikkei , Casco-Robles Martin Miguel , Taya Yuji , Yuzuriha Shunsuke , Toyama Fubito , Maruo Fumiaki , Kishi Kazuo , Chiba Chikafumi
Published: December 2021

In surgical and cosmetic studies, scarless regeneration is an ideal method to heal skin wounds. To study the technologies that enable scarless skin wound healing in medicine, animal models are useful. However, four-limbed vertebrates, including humans, generally lose their competency of scarless regeneration as they transit to their terrestrial life-stages through metamorphosis, hatching or birth. Therefore, animals that serve as a model for postnatal humans must be an exception to this rule, such as the newt. Here, we evaluated the adult newt in detail for the first time. Using a Japanese fire-bellied newt, Cynops pyrrhogaster, we excised the full-thickness skin at various locations on the body, and surveyed their re-epithelialization, granulation or dermal fibrosis, and recovery of texture and appendages as well as color (hue, tone and pattern) for more than two years. We found that the skin of adult newts eventually regenerated exceptionally well through unique processes of re-epithelialization and the absence of fibrotic scar formation, except for the dorsal-lateral to ventral skin whose unique color patterns never recovered. Color pattern is species-specific. Consequently, the adult C. pyrrhogaster provides an ideal model system for studies aimed at perfect skin wound healing and regeneration in postnatal humans.
miR-154 Influences HNSCC Development and Progression through Regulation of the Epithelial-to-Mesenchymal Transition Process and Could Be Used as a Potential Biomarker
Authors: Tomaszewska Weronika , Kozłowska-Masłoń Joanna , Baranowski Dawid , Perkowska Anna , Szałkowska Sandra , Kazimierczak Urszula , Severino Patricia , Lamperska Katarzyna , Kolenda Tomasz
Published: December 2021

MicroRNAs and their role in cancer have been extensively studied for the past decade. Here, we analyzed the biological role and diagnostic potential of miR-154-5p and miR-154-3p in head and neck squamous cell carcinoma (HNSCC). miRNA expression analyses were performed using The Cancer Genome Atlas (TCGA) data accessed from cBioPortal, UALCAN, Santa Cruz University, and Gene Expression Omnibus (GEO). The expression data were correlated with clinicopathological parameters. The functional enrichment was assessed with Gene Set Enrichment Analysis (GSEA). The immunological profiles were assessed using the ESTIMATE tool and RNAseq data from TCGA. All statistical analyses were performed with GraphPad Prism and Statistica. The study showed that both miR-154-5p and miR-154-3p were downregulated in the HNSCC samples and their expression levels correlated with tumor localization, overall survival, cancer stage, tumor grade, and HPV p16 status. GSEA indicated that individuals with the increased levels of miR-154 had upregulated AKT-MTOR, CYCLIN D1, KRAS, EIF4E, RB, ATM, and EMT gene sets. Finally, the elevated miR-154 expression correlated with better immune response. This study showed that miR-154 is highly involved in HNSCC pathogenesis, invasion, and immune response. The implementation of miR-154 as a biomarker may improve the effectiveness of HNSCC treatment.
Lactotransferrin Downregulation Serves as a Potential Predictor for the Therapeutic Effectiveness of mTOR Inhibitors in the Metastatic Clear Cell Renal Cell Carcinoma without PTEN Mutation
Authors: Zheng Jing-Quan , Lin Che-Hsuan , Lee Hsun-Hua , Wang Wen-Ke , Tong Yiu-Shun , Lee Kang-Yun , Chiu Hui-Wen , Lin Yuan-Feng
Published: December 2021

Approximately 30% of clear cell renal cell carcinoma (ccRCC) patients develop metastatic spread at the first diagnosis. Therefore, identifying a useful biomarker to predict ccRCC metastasis or therapeutic effectiveness in ccRCC patients is urgently needed. Previously, we demonstrated that lactotransferrin (LTF) downregulation enhanced the metastatic potential of ccRCC. Here, we show that LTF expression conversely associates with the mTORC1 activity as simulated by gene set enrichment analysis (GSEA). Moreover, Western blot analyses revealed that the LTF knockdown promoted, but the inclusion of recombinant human LTF protein suppressed, the phosphorylation of Akt/mTOR proteins in the detected ccRCC cells. Kaplan–Meier analyses demonstrated that the signature of combining an upregulated mTORC1 activity with a downregulated LTF expression referred to a worse overall and progression-free survival probabilities and associated with distant cancer metastasis in TCGA ccRCC patients. Furthermore, we found that the LTF-suppressed Akt/mTOR activation triggered an increased formation of autophagy in the highly metastatic ccRCC cells. The addition of autophagy inhibitor 3-methyadenine restored the LTF-suppressed cellular migration ability of highly metastatic ccRCC cells. Receiver operating characteristic (ROC) analyses showed that the expression of the LTF and MTORC1 gene set, not the autophagy gene set, could be the useful biomarkers to predict 5-year overall survival rate and cancer progression in ccRCC patients. Significantly, the signature of combining mTORC1 upregulation and LTF downregulation was shown as an independent prognostic factor in a multivariate analysis under the progression-free survival condition using the TCGA ccRCC database. Finally, the treatment with mTOR inhibitor rapamycin predominantly reduced the formation of autophagy and ultimately mitigated the cellular migration ability of ccRCC cells with LTF knockdown. Our findings suggest that LTF downregulation is a biomarker for guiding the use of mTOR inhibitors to combat metastatic ccRCC in the clinic.
Validation of Serum Biomarkers That Complement CA19-9 in Detecting Early Pancreatic Cancer Using Electrochemiluminescent-Based Multiplex Immunoassays
Authors: Song Jin , Sokoll Lori J. , Chan Daniel W. , Zhang Zhen
Published: December 2021

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy; its early detection is critical for improving prognosis. Electrochemiluminescent-based multiplex immunoassays were developed with high analytical performance. All proteins were analyzed in sera of patients diagnosed with PDAC (n = 138), benign pancreatic conditions (111), and healthy controls (70). The clinical performance of these markers was evaluated individually or in combination for their complementarity to CA19-9 in detecting early PDAC. Logistic regression modeling including sex and age as cofactors identified a two-marker panel of CA19-9 and CA-125 that significantly improved the performance of CA19-9 alone in discriminating PDAC (AUC: 0.857 vs. 0.766), as well as early stage PDAC (0.805 vs. 0.702) from intraductal papillary mucinous neoplasm (IPMN). At a fixed specificity of 80%, the panel significantly improved sensitivities (78% vs. 41% or 72% vs. 59%). A two-marker panel of HE4 and CEA significantly outperformed CA19-9 in separating IPMN from chronic pancreatitis (0.841 vs. 0.501). The biomarker panels evaluated by assays demonstrated potential complementarity to CA19-9 in detecting early PDAC, warranting additional clinical validation to determine their role in the early detection of pancreatic cancer.
Transcriptional Active Parvovirus B19 Infection Predicts Adverse Long-Term Outcome in Patients with Non-Ischemic Cardiomyopathy
Authors: Escher Felicitas , Aleshcheva Ganna , Pietsch Heiko , Baumeier Christian , Gross Ulrich M. , Schrage Benedikt Norbert , Westermann Dirk , Bock Claus-Thomas , Schultheiss Heinz-Peter
Published: December 2021

Parvovirus B19 (B19V) is the predominant cardiotropic virus currently found in endomyocardial biopsies (EMBs). However, direct evidence showing a causal relationship between B19V and progression of inflammatory cardiomyopathy are still missing. The aim of this study was to analyze the impact of transcriptionally active cardiotropic B19V infection determined by viral RNA expression upon long-term outcomes in a large cohort of adult patients with non-ischemic cardiomyopathy in a retrospective analysis from a prospective observational cohort. In total, the analyzed study group comprised 871 consecutive B19V-positive patients (mean age 50.0 ± 15.0 years) with non-ischemic cardiomyopathy who underwent EMB. B19V-positivity was ascertained by routine diagnosis of viral genomes in EMBs. Molecular analysis of EMB revealed positive B19V transcriptional activity in n = 165 patients (18.9%). Primary endpoint was all-cause mortality in the overall cohort. The patients were followed up to 60 months. On the Cox regression analysis, B19V transcriptional activity was predictive of a worse prognosis compared to those without actively replicating B19V (p = 0.01). Moreover, multivariable analysis revealed transcriptional active B19V combined with inflammation [hazard ratio 4.013, 95% confidence interval 1.515–10.629 (p = 0.005)] as the strongest predictor of impaired survival even after adjustment for age and baseline LVEF (p = 0.005) and independently of viral load. The study demonstrates for the first time the pathogenic clinical importance of B19V with transcriptional activity in a large cohort of patients. Transcriptionally active B19V infection is an unfavourable prognostic trigger of adverse outcome. Our findings are of high clinical relevance, indicating that advanced diagnostic differentiation of B19V positive patients is of high prognostic importance.
8-Hydroxydaidzein Downregulates JAK/STAT, MMP, Oxidative Phosphorylation, and PI3K/AKT Pathways in K562 Cells
Authors: Wu Pei-Shan , Wang Chih-Yang , Chen Pin-Shern , Hung Jui-Hsiang , Yen Jui-Hung , Wu Ming-Jiuan
Published: December 2021

A metabolite isolated from fermented soybean, 8-hydroxydaidzein (8-OHD, 7,8,4′-trihydroxyisoflavone, NSC-678112), is widely used in ethnopharmacological research due to its anti-proliferative and anti-inflammatory effects. We reported previously that 8-OHD provoked reactive oxygen species (ROS) overproduction, and induced autophagy, apoptosis, breakpoint cluster region-Abelson murine leukemia viral oncogene (BCR-ABL) degradation, and differentiation in K562 human chronic myeloid leukemia (CML) cells. However, how 8-OHD regulates metabolism, the extracellular matrix during invasion and metastasis, and survival signaling pathways in CML remains largely unexplored. High-throughput technologies have been widely used to discover the therapeutic targets and pathways of drugs. Bioinformatics analysis of 8-OHD-downregulated differentially expressed genes (DEGs) revealed that Janus kinase/signal transducer and activator of transcription (JAK/STAT), matrix metalloproteinases (MMPs), c-Myc, phosphoinositide 3-kinase (PI3K)/AKT, and oxidative phosphorylation (OXPHOS) metabolic pathways were significantly altered by 8-OHD treatment. Western blot analyses validated that 8-OHD significantly downregulated cytosolic JAK2 and the expression and phosphorylation of STAT3 dose- and time-dependently in K562 cells. Zymography and transwell assays also confirmed that K562-secreted MMP9 and invasion activities were dose-dependently inhibited by 8-OHD after 24 h of treatment. RT-qPCR analyses verified that 8-OHD repressed metastasis and OXPHOS-related genes. In combination with DisGeNET, it was found that 8-OHD’s downregulation of PI3K/AKT is crucial for controlling CML development. A STRING protein–protein interaction analysis further revealed that AKT and MYC are hub proteins for cancer progression. Western blotting revealed that AKT phosphorylation and nuclear MYC expression were significantly inhibited by 8-OHD. Collectively, this systematic investigation revealed that 8-OHD exerts anti-CML effects by downregulating JAK/STAT, PI3K/AKT, MMP, and OXPHOS pathways, and MYC expression. These results could shed new light on the development of 8-OHD for CML therapy.
Bioinspired and Post-Functionalized 3D-Printed Surfaces with Parahydrophobic Properties
Authors: Ciffréo Léna , Marchand Claire , Szczepanski Caroline R. , Medici Marie-Gabrielle , Godeau Guilhem
Published: December 2021

Desertification is a growing risk for humanity. Studies show that water access will be the leading cause of massive migration in the future. For this reason, significant research efforts are devoted to identifying new sources of water. Among this work, one of the more interesting strategies takes advantage of atmospheric non-liquid water using water harvesting. Various strategies exist to harvest water, but many suffer from low yield. In this work, we take inspiration from a Mexican plant (Echeveria pulvinate) to prepare a material suitable for future water harvesting applications. Observation of E. pulvinate reveals that parahydrophobic properties are favorable for water harvesting. To mimic these properties, we leveraged a combination of 3D printing and post-functionalization to control surface wettability and obtain parahydrophobic properties. The prepared surfaces were investigated using IR and SEM. The surface roughness and wettability were also investigated to completely describe the elaborated surfaces and strongly hydrophobic surfaces with parahydrophobic properties are reported. This new approach offers a powerful platform to develop parahydrophobic features with desired three-dimensional shape.