bluuebunny/crossref_metadata_2025 huggingface dataset:
Emotional State of Mexican University Students in the COVID-19 Pandemic
Authors: Dosil-Santamaria Maria , Ozamiz-Etxebarria Naiara , Idoiaga Mondragon Nahia , Reyes-Sosa Hiram , Santabárbara Javier
Published: February 2022

Background: Since the WHO declared the COVID-19 crisis a pandemic in March 2020, the young population is suffering from a range of psychological symptoms. The present study measured symptoms of stress, anxiety and depression in university students of Saltillo, Mexico, using the Depression and Anxiety Stress Scale-21 (DASS-21). Methods. The DASS-21 scale and an ad hoc questionnaire were used to collect sociodemographic information. Results: The results show that the students who participated in this study suffer from high levels of stress, anxiety and depression. In terms of sociodemographic variables, women, people suffering from a chronic disease and people living with a chronic disease had the highest levels of stress, anxiety and depression, and people who live with a chronically ill person, people who have had the COVID-19 disease and those who have had someone close to them fall sick have had more stress, anxiety and depression than the rest. Another finding of the present study is that university students who believe that others comply with COVID-19 safety measures have significantly lower anxiety and depression than those who believe that others do not comply. Conclusions: It is concluded that university students are a psychologically vulnerable group in the face of the pandemic.
Deep Learning Capabilities for the Categorization of Microcalcification
Authors: Kumar Singh Koushlendra , Kumar Suraj , Antonakakis Marios , Moirogiorgou Konstantina , Deep Anirudh , Kashyap Kanchan Lata , Bajpai Manish Kumar , Zervakis Michalis
Published: February 2022

Breast cancer is the most common cancer in women worldwide. It is the most frequently diagnosed cancer among women in 140 countries out of 184 reporting countries. Lesions of breast cancer are abnormal areas in the breast tissues. Various types of breast cancer lesions include (1) microcalcifications, (2) masses, (3) architectural distortion, and (4) bilateral asymmetry. Microcalcification can be classified as benign, malignant, and benign without a callback. In the present manuscript, we propose an automatic pipeline for the detection of various categories of microcalcification. We performed deep learning using convolution neural networks (CNNs) for the automatic detection and classification of all three categories of microcalcification. CNN was applied using four different optimizers (ADAM, ADAGrad, ADADelta, and RMSProp). The input images of a size of 299 × 299 × 3, with fully connected RELU and SoftMax output activation functions, were utilized in this study. The feature map was obtained using the pretrained InceptionResNetV2 model. The performance evaluation of our classification scheme was tested on a curated breast imaging subset of the DDSM mammogram dataset (CBIS–DDSM), and the results were expressed in terms of sensitivity, specificity, accuracy, and area under the curve (AUC). Our proposed classification scheme outperforms the ability of previously used deep learning approaches and classical machine learning schemes.
Risk Factors of Long-Term Care Insurance Certification in Japan: A Scoping Review
Authors: Takahashi Shuko , Yonekura Yuki , Takanashi Nobuyuki , Tanno Kozo
Published: February 2022

This study aimed to review evidence on future long-term care associated with pre-existing factors among community-dwelling Japanese older adults. We systematically searched cohort and nested case–control studies published between 2000 and 2019 that assessed long-term care certification using the PubMed, CINAHL, and EMBASE databases. The relationship between long-term care insurance information and risk factors was investigated. The protocol was registered with the Open Science Framework. We extracted 91 studies for synthesis, including 84 prospective cohort studies, 1 retrospective cohort study, and 6 nested case–control studies. Certification for long-term care was classified into two endpoints: onset of functional disability and dementia. There were 72 studies that used long-term care certification as a proxy for functional disability, and 22 used long-term care information to indicate the onset of dementia. Common risk factors related to functional disability were physical function, frailty, and oral condition. Motor function and nutritional status were common risk factors for dementia. We found consistent associations between premorbid risk factors and functional disability and dementia. The accumulation of evidence on the incidence of long-term care and associated factors can aid the development of preventive measures. Future studies should aim to integrate this evidence.
Mesenchymal Stromal Cells Preconditioning: A New Strategy to Improve Neuroprotective Properties
Authors: Schepici Giovanni , Gugliandolo Agnese , Mazzon Emanuela
Published: February 2022

Neurological diseases represent one of the main causes of disability in human life. Consequently, investigating new strategies capable of improving the quality of life in neurological patients is necessary. For decades, researchers have been working to improve the efficacy and safety of mesenchymal stromal cells (MSCs) therapy based on MSCs’ regenerative and immunomodulatory properties and multilinear differentiation potential. Therefore, strategies such as MSCs preconditioning are useful to improve their application to restore damaged neuronal circuits following neurological insults. This review is focused on preconditioning MSCs therapy as a potential application to major neurological diseases. The aim of our work is to summarize both the in vitro and in vivo studies that demonstrate the efficacy of MSC preconditioning on neuronal regeneration and cell survival as a possible application to neurological damage.
Targeting KRAS Regulation with PolyPurine Reverse Hoogsteen Oligonucleotides
Authors: Psaras Alexandra Maria , Valiuska Simonas , Noé Véronique , Ciudad Carlos J. , Brooks Tracy A.
Published: February 2022

KRAS is a GTPase involved in the proliferation signaling of several growth factors. The KRAS gene is GC-rich, containing regions with known and putative G-quadruplex (G4) forming regions. Within the middle of the G-rich proximal promoter, stabilization of the physiologically active G4mid structure downregulates transcription of KRAS; the function and formation of other G4s within the gene are unknown. Herein we identify three putative G4-forming sequences (G4FS) within the KRAS gene, explore their G4 formation, and develop oligonucleotides targeting these three regions and the G4mid forming sequence. We tested Polypurine Reverse Hoogsteen hairpins (PPRHs) for their effects on KRAS regulation via enhancing G4 formation or displacing G-rich DNA strands, downregulating KRAS transcription and mediating an anti-proliferative effect. Five PPRH were designed, two against the KRAS promoter G4mid and three others against putative G4FS in the distal promoter, intron 1 and exon 5. PPRH binding was confirmed by gel electrophoresis. The effect on KRAS transcription was examined by luciferase, FRET Melt2, qRT-PCR. Cytotoxicity was evaluated in pancreatic and ovarian cancer cells. PPRHs decreased activity of a luciferase construct driven by the KRAS promoter. PPRH selectively suppressed proliferation in KRAS dependent cancer cells. PPRH demonstrated synergistic activity with a KRAS promoter selective G4-stabilizing compound, NSC 317605, in KRAS-dependent pancreatic cells. PPRHs selectively stabilize G4 formation within the KRAS mid promoter region and represent an innovative approach to both G4-stabilization and to KRAS modulation with potential for development into novel therapeutics.
Zebrafish as a Model to Study Vascular Elastic Fibers and Associated Pathologies
Authors: Hoareau Marie , El Kholti Naïma , Debret Romain , Lambert Elise
Published: February 2022

Many extensible tissues such as skin, lungs, and blood vessels require elasticity to function properly. The recoil of elastic energy stored during a stretching phase is provided by elastic fibers, which are mostly composed of elastin and fibrillin-rich microfibrils. In arteries, the lack of elastic fibers leads to a weakening of the vessel wall with an increased risk to develop cardiovascular defects such as stenosis, aneurysms, and dissections. The development of new therapeutic molecules involves preliminary tests in animal models that recapitulate the disease and whose response to drugs should be as close as possible to that of humans. Due to its superior in vivo imaging possibilities and the broad tool kit for forward and reverse genetics, the zebrafish has become an important model organism to study human pathologies. Moreover, it is particularly adapted to large scale studies, making it an attractive model in particular for the first steps of investigations. In this review, we discuss the relevance of the zebrafish model for the study of elastic fiber-related vascular pathologies. We evidence zebrafish as a compelling alternative to conventional mouse models.
Effect of Oxidative Stress-Induced Apoptosis on Active FGF23 Levels in MLO-Y4 Cells: The Protective Role of 17-β-Estradiol
Authors: Domazetovic Vladana , Falsetti Irene , Ciuffi Simone , Iantomasi Teresa , Marcucci Gemma , Vincenzini Maria Teresa , Brandi Maria Luisa
Published: February 2022

The discovery that osteocytes secrete phosphaturic fibroblast growth factor 23 (FGF23) has defined bone as an endocrine organ. However, the autocrine and paracrine functions of FGF23 are still unknown. The present study focuses on the cellular and molecular mechanisms involved in the complex control of FGF23 production and local bone remodeling functions. FGF23 was assayed using ELISA kit in the presence or absence of 17β–estradiol in starved MLO-Y4 osteocytes. In these cells, a relationship between oxidative stress-induced apoptosis and up-regulation of active FGF23 levels due to MAP Kinases activation with involvement of the transcriptional factor (NF-kB) has been demonstrated. The active FGF23 increase can be due to up-regulation of its expression and post-transcriptional modifications. 17β–estradiol prevents the increase of FGF23 by inhibiting JNK and NF-kB activation, osteocyte apoptosis and by the down-regulation of osteoclastogenic factors, such as sclerostin. No alteration in the levels of dentin matrix protein 1, a FGF23 negative regulator, has been determined. The results of this study identify biological targets on which drugs and estrogen may act to control active FGF23 levels in oxidative stress-related bone and non-bone inflammatory diseases.
Alteration of Ethanol Reward by Prior Mephedrone Exposure: The Role of Age and Matrix Metalloproteinase-9 (MMP-9)
Authors: Grochecki Pawel , Smaga Irena , Marszalek-Grabska Marta , Lopatynska-Mazurek Malgorzata , Slowik Tymoteusz , Gibula-Tarlowska Ewa , Kedzierska Ewa , Listos Joanna , Filip Malgorzata , Kotlinska Jolanta H.
Published: February 2022

Mephedrone, a synthetic cathinone, is widely abused by adolescents and young adults. The aim of this study was to determine: (i) whether prior mephedrone exposure would alter ethanol reward and (ii) whether age and matrix metalloproteinase-9 (MMP-9) are important in this regard. In our research, male Wistar rats at postnatal day 30 (PND30) received mephedrone at the dose of 10 mg/kg, i.p., 3 times a day for 7 days. To clarify the role of MMP-9 in the mephedrone effects, one mephedrone-treated group received minocycline, as an MMP-9 antagonist. Animals were then assigned to conditioned place preference (CPP) procedure at PND38 (adolescent) or at PND69 (adult). After the CPP test (PND48/79), expression of dopamine D1 receptors (D1R), Cav1.2 (a subtype of L-type calcium channels), and MMP-9 was quantified in the rat ventral striatum (vSTR). The influence of mephedrone administration on the N-methyl-D-aspartate glutamate receptors (NMDAR) subunits (GluN1, GluN2A, and GluN2B) was then assessed in the vSTR of adult rats (only). These results indicate that, in contrast with adolescent rats, adult rats with prior mephedrone administration appear to be more sensitive to the ethanol effect in the CPP test under the drug-free state. The mephedrone effect in adult rats was associated with upregulation of D1R, NMDAR/GluN2B, MMP-9, and Cav1.2 signaling. MMP-9 appears to contribute to these changes in proteins expression because minocycline pretreatment blocked mephedrone-evoked sensitivity to ethanol reward. Thus, our results suggest that prior mephedrone exposure differentially alters ethanol reward in adolescent and adult rats.
Detection and Modulation of Olfactory Sensing Receptors in Carnivorous Rainbow Trout (Oncorhynchus mykiss) Fed from First Feeding with Plant-Based Diet
Authors: Heraud Cécile , Hirschinger Théo , Baranek Elodie , Larroquet Laurence , Surget Anne , Sandres Franck , Lanuque Anthony , Terrier Frederic , Roy Jérôme
Published: February 2022

Sense of smell is mediated by diverse families of olfactory sensing receptors, conveying important dietary information, fundamental for growth and survival. The aim of this study was to elucidate the role of the sensory olfactory pathways in the regulation of feeding behavior of carnivorous rainbow trout (RT, Oncorhynchus mykiss), from first feeding until 8 months. Compared to a commercial diet, RT fed with a total plant-based diet showed drastically altered growth performance associated with feed intake from an early stage. Exhaustive examination of an RT genome database identified three vomeronasal type 1 receptor-like (ORA), 10 vomeronasal type 2 receptor-like (OLFC) and 14 main olfactory receptor (MOR) genes, all highly expressed in sensory organs, indicating their potential functionality. Gene expression after feeding demonstrated the importance in olfactory sensing perception of some OLFC (olfcg6) and MOR (mor103, -107, -112, -113, -133) receptor family genes in RT. The gene ora1a showed evidence of involvement in olfactory sensing perception for fish fed with a commercial-like diet, while ora5b, mor118, mor124 and olfch1 showed evidence of involvement in fish fed with a plant-based diet. Results indicated an impact of a plant-based diet on the regulation of olfactory sensing pathways as well as influence on monoaminergic neurotransmission in brain areas related to olfactory-driven behaviors. The overall findings suggest that feeding behavior is mediated through olfactory sensing detection and olfactory-driven behavior pathways in RT.
Aeroelastic Stability of Combined Plunge-Pitch Mode Shapes in a Linear Compressor Cascade
Authors: Hill George , Gambel Julian , Schneider Sabine , Peitsch Dieter , Stapelfeldt Sina
Published: February 2022

Modern aeroengine designs strive for peak specific fuel and thermal efficiency. To achieve these goals, engines have more highly loaded compressor stages, thinner aerofoils, and blended titanium integrated disks (blisks) to reduce weight. These configurations promote the occurrence of aeroelastic phenomena such as flutter. Two important parameters known to influence flutter stability are the reduced frequency and the ratio of plunge and pitch components in a combined flap mode shape. These are used as design criteria in the engine development process. However, the limit of these criteria is not fully understood. The following research aims to bridge the gap between semi-analytical models and modern compressors by systematically investigating the flutter stability of a linear compressor cascade. This paper introduces the plunge-to-pitch incidence ratio, which is defined as a function of reduced frequency and pitch axis setback for a first flap (1F) mode shape. Using numerical simulations, in addition to experimental validation, aerodynamic damping is computed for many modes to build stability maps. The results confirm the importance of these two parameters in compressor aeroelastic stability as well as demonstrate the significance of the plunge-to-pitch incidence ratio for predicting the flutter limit.
Numerical Prediction of Convective Heat Flux on the Flight Deck of Naval Vessel Subjected to a High-Speed Jet Flame from VTOL Aircraft
Authors: Jang Ho-Sang , Hwang Se-Yun , Lee Jang-Hyun
Published: February 2022

This study examines the heat flux and convective heat transfer generated when a vertical take-off and landing (VTOL) aircraft takes off and lands on the flight deck of a naval vessel. A procedure for analyzing the convective heat transfer imposed on the deck by the high-temperature and high-velocity impingement of a VTOL jet is described. For the analysis, the jet velocity and the deck arrival temperature were calculated by applying computational fluid dynamics (CFD), assuming that the heat flow is an impingement jet. The relationships between the diameter of the jet, the speed of impingement, and the exhaust temperature of VTOL are introduced to assess the inlet condition. Heat flow was analyzed using CFD techniques, and Reynolds-averaged Navier–Stokes (RANS) and k-ε models were applied to model the turbulent motion. A procedure for evaluating the convection coefficient and convective heat flux from the calculated local velocity and temperature is presented. Simultaneously, a method for compensating the convection coefficient considering the singular velocity at the stagnation point is proposed. Furthermore, the accuracy was verified by comparing the convective heat flux and deck temperature predicted using CFD with the existing experimental studies. Finally, by applying finite element analysis (FEA) based on the thermal-structural interaction, the magnitude of thermal deformation due to conductive temperature and heat flux was presented as a design application of the flight deck.
Do Ethical Companies Have High Stock Prices or High Returns?
Authors: Yu Bing , Wu Shengxiong , Lenard Mary Jane
Published: February 2022

In this paper, we examine the performance of an impact investing strategy using the most ethical companies to build an impact investing portfolio. We test the time-series and cross-sectional returns of the impact portfolio, explore the financial analyst coverage of the most ethical firms, and run regressions to analyze the valuation of the most ethical firms. Our empirical results reveal that the portfolio consisting of the most ethical firms has a higher risk-adjusted return and that the most ethical firms have lower stock valuations than comparable stocks. We attribute our findings to the incomplete information in business ethics norms.
Linguistic Landscapes in the Stockholm Archipelago—Producing and Reflecting a Sense of Place
Authors: Syrjälä Väinö
Published: February 2022

This article takes a look at the linguistic landscapes of the Stockholm archipelago with the aim to discuss if, and how, a specific sense of place is produced or reflected in the signs, building on Lefebvre’s concept of social spaces. Signs collected from two islands, Nämdö and Svartsö, are used in qualitative analysis. Firstly, the construction of such a (rural) linguistic landscape is discussed, focusing on the languages used as well as the emplacement and general functions of signs. Secondly, a closer look at some examples from the linguistic landscape provides insight into signs that are speaking to locals and visitors. The analysis shows that the linguistic landscape is almost exclusively made up of signs in Swedish. Functionally, a variety of different signs can be found, partly centred by local businesses, and on bulletin boards, but many signs with general information and instructions can also be found throughout the landscape. Examples of signs addressing both permanent residents and visitors can be identified, but the general sense of place the linguistic landscapes reflect is that of more organic places, not overly produced or touristic ones.
Passive Photonic Integrated Circuits Elements Fabricated on a Silicon Nitride Platform
Authors: Lelit Marcin , Słowikowski Mateusz , Filipiak Maciej , Juchniewicz Marcin , Stonio Bartłomiej , Michalak Bartosz , Pavłov Krystian , Myśliwiec Marcin , Wiśniewski Piotr , Kaźmierczak Andrzej , Anders Krzysztof , Stopiński Stanisław , Beck Romuald B. , Piramidowicz Ryszard
Published: February 2022

The fabrication processes for silicon nitride photonic integrated circuits evolved from microelectronics components technology—basic processes have common roots and can be executed using the same type of equipment. In comparison to that of electronics components, passive photonic structures require fewer manufacturing steps and fabricated elements have larger critical dimensions. In this work, we present and discuss our first results on design and development of fundamental building blocks for silicon nitride integrated photonic platform. The scope of the work covers the full design and manufacturing chain, from numerical simulations of optical elements, design, and fabrication of the test structures to optical characterization and analysis the results. In particular, technological processes were developed and evaluated for fabrication of the waveguides (WGs), multimode interferometers (MMIs), and arrayed waveguide gratings (AWGs), which confirmed the potential of the technology and correctness of the proposed approach.
Evaluation of the Performance of a Composite Profile at Elevated Temperatures Using Finite Element and Hybrid Artificial Intelligence Techniques
Authors: Ding Wangfei , Alharbi Abdullah , Almadhor Ahmad , Rahnamayiezekavat Payam , Mohammadi Masoud , Rashidi Maria
Published: February 2022

It is very important to keep structures and constructional elements in service during and after exposure to elevated temperatures. Investigation of the structural behaviour of different components and structures at elevated temperatures is an approach to manipulate the serviceability of the structures during heat exposure. Channel connectors are widely used shear connectors not only for their appealing mechanical properties but also for their workability and cost-effective nature. In this study, a finite element (FE) evaluation was performed on an authentic composite model, and the behaviour of the channel shear connector at elevated temperature was examined. Furthermore, a novel hybrid intelligence algorithm based on a feature-selection trait with the incorporation of particle swarm optimization (PSO) and multi-layer perceptron (MLP) algorithms has been developed to predict the slip response of the channel. The hybrid intelligence algorithm that uses artificial neural networks is performed on derived data from the FE study. Finally, the obtained numerical results are compared with extreme learning machine (ELM) and radial basis function (RBF) results. The MLP-PSO represented dramatically accurate results for slip value prediction at elevated temperatures. The results proved the active presence of the channels, especially to improve the stiffness and loading capacity of the composite beam. Although the height enhances the ductility, stiffness is significantly reduced at elevated temperatures. According to the results, temperature, failure load, the height of connector and concrete block strength are the key governing parameters for composite floor design against high temperatures.
Experimental and Numerical Study on the Failure Characteristics of Brittle Solids with a Circular Hole and Internal Cracks
Authors: Le Chengjun , Ren Xuhua , Wang Haijun , Yu Shuyang
Published: February 2022

A stress analysis of a circular hole is one of the classical problems in mechanics. Internal cracks are inherent properties of materials, and they are mostly three-dimensional in form. However, studies on hole problems with three-dimensional internal cracks are still lacking. In this paper, internal cracks were generated in brittle materials containing circular holes based on 3D internal laser-engraved crack technology. Then, uniaxial compression tests were performed. The experimental results were compared with the existing literature, and theoretical and numerical simulation studies were carried out. The results show that: (1) The main crack shapes are the primary cracks and remote cracks. (2) The dynamic fracture characteristics existed in the formation of primary cracks and the surface of remote cracks. The tips of primary cracks were arc-shaped, and the surfaces of the remote cracks were curved. Remote cracks were tangential to the orifice where type III spear-like characteristics appeared. (3) The stress birefringence technology can be combined with 3D internal laser-engraved crack technology for internal crack stress information monitoring, the moire around the orifice was “flamboyant”, and the moire at the tip of the prefabricated crack was “petallike”. (4) The existence of internal cracks reduced the cracking and breaking load of the specimen, and compared with the intact orifice specimen, the upper primary crack, the lower primary crack, the remote crack and the failure load were reduced by 41.2%, 31.7%, 15.9%, and 32.3%, respectively. (5) The results of qualitative stress analysis of the orifice specimen were consistent with the initiation law of primary cracks and remote cracks. The K distribution based on M integral and the numerical simulation of crack propagation process based on the maximum tensile stress criterion were consistent with the law of primary crack growth. Compared with the current mainstream method of transparent rock research, 3D internal laser-engraved crack technology has certain advantages in terms of brittleness, crack authenticity, stress field visualization, and fracture characteristics, and the result will provide experimental and theoretical references for research on three-dimensional problems and internal cracks in fracture mechanics.
Effect of Ageing on Self-Healing Properties of Asphalt Concrete Containing Calcium Alginate/Attapulgite Composite Capsules
Authors: Yu Xin , Liu Quantao , Wan Pei , Song Jiangkai , Wang Huan , Zhao Feiyang , Wang Yafei , Wu Jinyi
Published: February 2022

Calcium alginate capsules within asphalt concrete can gradually release interior asphalt rejuvenator under cyclic loading to repair micro cracks and rejuvenate aged asphalt in-situ. However, asphalt pavement will become aged due to environmental and traffic factors during the service period. In view of this, this paper investigated the effect of ageing on the healing properties of asphalt concrete containing calcium alginate/attapulgite composite capsules under cyclic loading. The capsules were fabricated using the orifice-bath method and the morphological structure, mechanical strength, thermal stability, oil release ratios and healing levels of capsules in fresh, short-term ageing and long-term ageing asphalt concrete were explored. The results indicated that the different ageing treatments would not damage the multi-chamber structure nor decrease the mechanical strength of capsules but would induce the capsules release oil prematurely. The premature oil released from capsules in turn can offset the ageing effect owing to ageing treatment. The short-term ageing and long-term ageing plain asphalt mixtures gained strength recovery ratios of 39.3% and 34.2% after 64,000 cycles of compression loading, while the strength recovery ratios of short-term ageing and long-term ageing asphalt mixtures containing capsules were 63.5% and 54.8%, respectively.
Induction Heating in Underwater Wet Welding—Thermal Input, Microstructure and Diffusible Hydrogen Content
Authors: Brätz Oliver , Klett Jan , Wolf Thomas , Henkel Knuth-Michael , Maier Hans Jürgen , Hassel Thomas
Published: February 2022

Hydrogen-assisted cracking is a major challenge in underwater wet welding of high-strength steels with a carbon equivalent larger than 0.4 wt%. In dry welding processes, post-weld heat treatment can reduce the hardness in the heat-affected zone while simultaneously lowering the diffusible hydrogen concentration in the weldment. However, common heat treatments known from atmospheric welding under dry conditions are non-applicable in the wet environment. Induction heating could make a difference since the heat is generated directly in the workpiece. In the present study, the thermal input by using a commercial induction heating system under water was characterized first. Then, the effect of an additional induction heating was examined with respect to the resulting microstructure of weldments on structural steels with different strength and composition. Moreover, the diffusible hydrogen content in weld metal was analyzed by the carrier gas hot extraction method. Post-weld induction heating could reduce the diffusible hydrogen content by −34% in 30 m simulated water depth.
Statistical Analysis of Current Financial Instrument Quotes in the Conditions of Market Chaos
Authors: Musaev Alexander , Makshanov Andrey , Grigoriev Dmitry
Published: February 2022

In this paper, the problem of estimating the current value of financial instruments using multidimensional statistical analysis is considered. The research considers various approaches to constructing regression computational schemes using quotes of financial instruments correlated to the data as regressors. An essential feature of the problem is the chaotic nature of its observation series, which is due to the instability of the probabilistic structure of the initial data. These conditions invalidate the constraints under which traditional statistical estimates remain non-biased and effective. Violation of experiment repeatability requirements obstructs the use of the conventional data averaging approach. In this case, numeric experiments become the main method for investigating the efficiency of forecasting and analysis algorithms of observation series. The empirical approach does not provide guaranteed results. However, it can be used to build sufficiently effective rational strategies for managing trading operations.
Remitting Seronegative Symmetrical Synovitis with Pitting Edema Syndrome Worsen after the Administration of Dulaglutide
Authors: Sawamura Toshitaka , Karashima Shigehiro , Ohmori Ai , Sawada Kei , Kometani Mitsuhiro , Takeda Yoshiyu , Yoneda Takashi
Published: February 2022

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome is characterized by symmetrical polyarthritis and limb pitting edema. Although the detailed mechanisms of this syndrome have not been clearly understood, some agents including dipeptidyl peptidase-4 inhibitors have been reported to induce RS3PE syndrome. However, glucagon-like peptide-1 (GLP-1) analogues have not been reported to be associated with this syndrome. A 91-year-old woman was admitted to our hospital with complaints of severe polyarthritis and limb edema. She was diagnosed with RS3PE syndrome. Oral prednisolone improved her symptoms. However, her symptoms worsened after the administration of dulaglutide, with elevated serum inflammatory markers. Discontinuation of dulaglutide without additional treatment improved her symptoms and laboratory findings. This case might indicate the possibility of development and worsening of RS3PE syndrome caused after GLP-1 analogue.
Nash Up, Virus Down: How the Waiting List Is Changing for Liver Transplantation: A Single Center Experience from Italy
Authors: Ferrarese Alberto , Battistella Sara , Germani Giacomo , Russo Francesco Paolo , Senzolo Marco , Gambato Martina , Vitale Alessandro , Cillo Umberto , Burra Patrizia
Published: February 2022

Background and Objectives: Non-alcoholic steatohepatitis (NASH) has become the leading indication for liver transplantation in many countries, with a growing rate in the Western world. NASH patients are older and share a higher risk of comorbidities and cancer than patients with viral and/or alcoholic etiologies. The aims of this study were to evaluate waiting list (WL) registration and liver transplantation rates in patients with NASH-related cirrhosis at Padua University Hospital in the last fifteen years (1.2006–6.2020) and to compare clinical characteristics and indications for liver transplantation between patients with and without NASH, as well as the WL survival and post-transplant outcome. Materials and Methods: All adult patients with cirrhosis listed for liver transplantation at Padua University Hospital between 1.2006 and 6.2020 were retrospectively collected using a prospectively updated database; patients with NASH-related cirrhosis were divided by indication for liver transplantation (Dec-NASH vs. hepatocellular carcinoma (HCC)-NASH) and compared with patients with other etiologies of liver disease. The outcomes in terms of waiting list survival and post-transplant outcome were assessed. Results: One thousand four hundred and ninety-one adult cirrhotic patients were waitlisted during the study period. NASH patients accounted for 12% of all WL registrations, showing an increasing trend over time (from 2.5% in 2006 to 23% in 2020). In the last five years, NASH was the third, but most rapidly growing, indication for liver transplantation at our center. This trend was confirmed both for patients with decompensated cirrhosis (from 1.8% to 18%) and HCC as leading indication for transplantation (from 4% to 30%). NASH patients were older than non-NASH ones (mean ± SD age 59 ± 9 vs. 56 ± 9 years; p < 0.01), whereas no difference was found in gender or Child-Pugh of the model for end-stage liver disease score at WL registration. A majority (60.9%) of NASH patients underwent liver transplantation, showing 1-, 5- and 10-y post-transplant survivals of 86%, 73% and 60%, respectively. Conclusion: NASH cirrhosis has become a rapidly growing indication for liver transplantation at our center, both for HCC and decompensated disease, with good post-transplant survival.
Interaction Characterization of a Tyrosine Kinase Inhibitor Erlotinib with a Model Transport Protein in the Presence of Quercetin: A Drug–Protein and Drug–Drug Interaction Investigation Using Multi-Spectroscopic and Computational Approaches
Authors: Wani Tanveer A. , Alanazi Mohammed M. , Alsaif Nawaf A. , Bakheit Ahmed H. , Zargar Seema , Alsalami Ommalhasan Mohammed , Khan Azmat Ali
Published: February 2022

The interaction between erlotinib (ERL) and bovine serum albumin (BSA) was studied in the presence of quercetin (QUR), a flavonoid with antioxidant properties. Ligands bind to the transport protein BSA resulting in competition between different ligands and displacing a bound ligand, resulting in higher plasma concentrations. Therefore, various spectroscopic experiments were conducted in addition to in silico studies to evaluate the interaction behavior of the BSA-ERL system in the presence and absence of QUR. The quenching curve and binding constants values suggest competition between QUR and ERL to bind to BSA. The binding constant for the BSA-ERL system decreased from 2.07 × 104 to 0.02 × 102 in the presence of QUR. The interaction of ERL with BSA at Site II is ruled out based on the site marker studies. The suggested Site on BSA for interaction with ERL is Site I. Stability of the BSA-ERL system was established with molecular dynamic simulation studies for both Site I and Site III interaction. In addition, the analysis can significantly help evaluate the effect of various quercetin-containing foods and supplements during the ERL-treatment regimen. In vitro binding evaluation provides a cheaper alternative approach to investigate ligand-protein interaction before clinical studies.
Highly Fluorescent Dyes Containing Conformationally Restrained Pyrazolylpyrene (Pyrazoolympicene) Chromophore
Authors: Wrona-Piotrowicz Anna , Makal Anna , Zakrzewski Janusz
Published: February 2022

The triflic-acid-promoted cyclization of 1-phenyl-3-(pyren-1-yl)-1H-pyrazole-4-carbaldehyde afforded a mixture of 9-phenyl-7,9-dihydropyreno (10,1-fg)indazole and 9-phenylpyreno(10,1-fg)indazole-7(9H)-one, readily separable by column chromatography. Both products contained a rigid six-ringed pyrazoolympicene backbone and exhibited bright fluorescence in chloroform solution and a weak fluorescence in the solid state. DFT and TD DFT calculations revealed that the lowest excited state (S1) of these compounds is populated via HOMO →LUMO π-π * transition. Furthermore, the synthesized compounds behaved as weak bases and their emission spectra showed substantial changes upon protonation. Therefore, they may be of interest for sensing of strongly acidic fluorophore environments.
Evaluation of Nutritional Substances and Investigation of Antioxidant and Antimicrobial Potentials of Boerhavia diffusa with in Silico Molecular Docking
Authors: Kaviya Mohandass , Balasubramanian Balamuralikrishnan , Bharathi Kathirvel , Malaisamy Arunkumar , Al-Dhabi Naif Abdullah , Mariadhas Valan Arasu , Anand Arumugam Vijaya , Liu Wenchao
Published: February 2022

Boerhavia diffusa L. Nyctanginaceae (B. diffusa) is a medicinal herb commonly considered as a weed. The exploration of phytochemicals in different parts of B. diffusa with different solvents will create awareness, along with the suitable solvent and method for extraction of pharmaceutical compounds. Hence, the present study focuses on phytochemical analysis of B. diffusa leaves, stems, and roots in various solvents with hot and cold extraction. The decoctions performed well in most of the qualitative and quantitative tests, along with the DPPH assay. The aqueous extract showed a good result in the FRAP assay and ABTS assay. In the antimicrobial test, the B. diffusa root ethanol extract inhibited the growth of Pseudomonas aeruginosa and Staphylococcus aureus with zones of inhibition of about 8 mm and 20 mm at 200 µg concentration, respectively. Using a molecular docking approach, the top four ranked molecules from the crude extract of B. diffusa profiled from GC–MS spectroscopy in terms of growth inhibition of the pathogenic bacterium P. aeruginosa were selected; among them, 2-(1,2 dihydroxyethyl)-5-[[2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-3,4-dihydrochromen-6-yl]oxy]oxolane-3,4-diol exhibited the minimum binding score, revealing high affinity in complex. B. diffusa is highly nutritious, and the maceration and decoction extracts were similar except for the chloroform extract that was found to be weak.
Risedronate and Methotrexate Are High-Affinity Inhibitors of New Delhi Metallo-β-Lactamase-1 (NDM-1): A Drug Repurposing Approach
Authors: Muteeb Ghazala , Alsultan Abdulrahman , Farhan Mohd , Aatif Mohammad
Published: February 2022

Bacteria expressing New Delhi metallo-β-lactamase-1 (NDM-1) can hydrolyze β-lactam antibiotics (penicillins, cephalosporins, and carbapenems) and, thus, mediate multidrug resistance. The worldwide dissemination of NDM-1 poses a serious threat to public health, imposing a huge economic burden in the development of new antibiotics. Thus, there is an urgent need for the identification of novel NDM-1 inhibitors from a pool of already-known drug molecules. Here, we screened a library of FDA-approved drugs to identify novel non-β-lactam ring-containing inhibitors of NDM-1 by applying computational as well as in vitro experimental approaches. Different steps of high-throughput virtual screening, molecular docking, molecular dynamics simulation, and enzyme kinetics were performed to identify risedronate and methotrexate as the inhibitors with the most potential. The molecular mechanics/generalized Born surface area (MM/GBSA) and molecular dynamics (MD) simulations showed that both of the compounds (risedronate and methotrexate) formed a stable complex with NDM-1. Furthermore, analyses of the binding pose revealed that risedronate formed two hydrogen bonds and three electrostatic interactions with the catalytic residues of NDM-1. Similarly, methotrexate formed four hydrogen bonds and one electrostatic interaction with NDM-1’s active site residues. The docking scores of risedronate and methotrexate for NDM-1 were –10.543 kcal mol−1 and −10.189 kcal mol−1, respectively. Steady-state enzyme kinetics in the presence of risedronate and methotrexate showed a decreased catalytic efficiency (i.e., kcat/Km) of NDM-1 on various antibiotics, owing to poor catalytic proficiency and affinity. The results were further validated by determining the MICs of imipenem and meropenem in the presence of risedronate and methotrexate. The IC50 values of the identified inhibitors were in the micromolar range. The findings of this study should be helpful in further characterizing the potential of risedronate and methotrexate to treat bacterial infections.
Photoinduced Bisphosphination of Alkynes with Phosphorus Interelement Compounds and Its Application to Double-Bond Isomerization
Authors: Yamamoto Yuki , Tanaka Ryo , Kodama Shintaro , Nomoto Akihiro , Ogawa Akiya
Published: February 2022

The addition of interelement compounds with heteroatom-heteroatom single bonds to carbon-carbon unsaturated bonds under light irradiation is believed to be an atomically efficient method to procure materials with carbon-heteroatom bonds. In this study, we achieved the photoinduced bisphosphination of alkynes using the phosphorus interelement compound, tetraphenyldiphosphine monosulfide (1), to stereoselectively obtain the corresponding (E)-vic-1,2-bisphosphinoalkenes, which are important transition-metal ligands. The bisphosphination reaction was performed by mixing 1 and various alkynes and then exposing the mixture to light irradiation. Optimization of the conditions for the bisphosphination reaction resulted in a wide substrate range and excellent trans-selectivity. Moreover, the completely regioselective introduction of pentavalent and trivalent phosphorus groups to the terminal and internal positions of the alkynes, respectively, was achieved. We also found that the novel double-bond isomerization reaction of the synthesized bisphosphinated products occurred with a catalytic amount of a base under mild conditions. Our method for the photoinduced bisphosphination of carbon-carbon unsaturated compounds may have strong implications for both organic synthesis and organometallic and catalyst chemistry.
Types and Aspects of Front-of-Package Labeling Preferred by Parents: Insights for Policy Making in China
Authors: Cui Jia , Yan Ruijie , Astell-Burt Thomas , Gong Enying , Zheng Lutong , Li Xinxuan , Zhang Jingwen , Xiang Lin , Ye Lihong , Hu Yiluan , Tang Yuxiang , Gao Chao , Xiao Li , Jiang Yan , Shao Ruitai , Feng Xiaoqi , Zhang Juan , Yang Yuexin
Published: February 2022

The WHO recommends front-of-package labeling (FOPL) to help parents make healthier food choices for their children. But which type of FOPL resonates with parents in China? We performed a cross-sectional study to investigate parental preferences for five widely used formats of FOPL. A multi-stage cluster sampling method was applied to selected parents of students in primary and secondary schools in six provinces and municipalities from July 2020 to March 2021. A close-ended questionnaire was used to collect demographic information, parents’ preferences for five FOPL in three dimensions, perceptions of the importance of nutrients labeled on FOPL, and prepackaged foods that need FOPL most. Chi-square tests were used to examine the characteristics among five groups. The results showed that multiple traffic lights (MTL) was preferred by parents, followed by warning labels. Parents thought the most needed nutrients to label were sugar, salt, and total fat. The top three prepackaged foods to label were “baked food”, “milk and dairy products” and “sugar-sweetened beverages”. Our findings indicate that nutrient-specific FOPL formats with interpretive aids were preferred by Chinese parents. These new findings can help inform the planning and implementation of FOPL in China and help Chinese parents make healthier food choices.
Vitamin D Status and Health Outcomes in School Children in Northern Ireland: Year One Results from the D-VinCHI Study
Authors: Glatt Dominique Ulrike , McSorley Emeir , Pourshahidi L. Kirsty , Revuelta Iniesta Raquel , McCluskey Jane , Beggan Laura , Slevin Mary , Gleeson Nigel , Cobice Diego F. , Dobbin Sara , Magee Pamela J.
Published: February 2022

(1) Background: Vitamin D status has never been investigated in children in Northern Ireland (UK). (2) Methods: Children (4–11 years) (n = 47) were recruited from November 2019 to March 2020 onto the cross-sectional study. Anthropometry was assessed. Plasma 25-hydroxyvitamin D (25(OH)D) was analysed. Vitamin D intake, parental knowledge and perceptions, participant habits, physical activity and sedentary behaviour were established via questionnaire. Muscle strength was assessed via isometric grip strength dynamometry and balance via dominant single-leg and tandem stance. Parathyroid hormone, bone turnover markers (OC, CTX and P1NP), glycated haemoglobin and inflammatory markers (CRP, IFN-γ, IL-10, IL-12p70, IL-13, IL-1β, IL-2, IL-4, IL-6, IL-8 and TNF-α) were analysed. (3) Results: Mean (SD) 25(OH)D was 49.17 (17.04) nmol/L (n = 47); 44.7% of the children were vitamin D sufficient (25(OH)D >50 nmol/L), 48.9% were insufficient (25–50 nmol/L) and 6.4% were deficient (<25 nmol/L). 25(OH)D was positively correlated with vitamin D intake (µg/day) (p = 0.012, r = 0.374), spring/summer outdoor hours (p = 0.006, r = 0.402) and dominant grip strength (kg) (p = 0.044, r = 0.317). Vitamin D sufficient participants had higher dietary vitamin D intake (µg/day) (p = 0.021), supplement intake (µg/day) (p = 0.028) and spring/summer outdoor hours (p = 0.015). (4) Conclusion: Over half of the children were vitamin D deficient or insufficient. Wintertime supplementation, the consumption of vitamin D rich foods and spring/summer outdoor activities should be encouraged to minimise the risk of vitamin D inadequacy.
Evaluation of Fluorescence Intensity and Antitumor Effect Using Real-Time Imaging in Photoimmunotherapy
Authors: Takashima Kenji , Koga Yoshikatsu , Anzai Takahiro , Migita Kayo , Yamaguchi Toru , Ishikawa Akihiro , Sakashita Shingo , Yasunaga Masahiro , Yano Tomonori
Published: February 2022

Photoimmunotherapy (PIT) is a promising tumor-selective treatment method that uses light-absorbing dye-conjugated antibodies and light irradiation. It has been reported that IR700 fluorescence changes with light irradiation. The purpose of this study was to investigate the fluorescence intensity and antitumor effect of PIT using real-time fluorescence observation of tumors and predict the required irradiation dose. The near-infrared camera system LIGHTVISION was used to image IR700 during PIT treatment. IR700 showed a sharp decrease in fluorescence intensity in the early stage of treatment and almost reached a plateau at an irradiation dose of 40 J/cm. Cetuximab-PIT for A431 xenografts was performed at multiple doses from 0–100 J/cm. A significant antitumor effect was observed at 40 J/cm compared to no irradiation, and there was no significant difference between 40 J/cm and 100 J/cm. These results suggest that the rate of decay of the tumor fluorescence intensity correlates with the antitumor effect by real-time fluorescence imaging during PIT. In addition, when the fluorescence intensity of the tumor plateaued in real-time fluorescence imaging, it was assumed that the laser dose was necessary for treatment.
Experimental Nuclear Medicine Meets Tumor Biology
Authors: Balber Theresa , Tran Loan , Benčurová Katarína , Raitanen Julia , Egger Gerda , Mitterhauser Markus
Published: February 2022

Personalized treatment of cancer patients demands specific and validated biomarkers for tumor diagnosis and therapy. The development and validation of such require translational preclinical models that recapitulate human diseases as accurately as possible. Moreover, there is a need for convergence of different (pre)clinical disciplines that openly share their knowledge and methodologies. This review sheds light on the differential perception of biomarkers and gives an overview of currently used models in tracer development and approaches for biomarker discovery.