bluuebunny/crossref_metadata_2025 huggingface dataset:
ODPA-CNN: One Dimensional Parallel Atrous Convolution Neural Network for Band-Selective Hyperspectral Image Classification
Authors: Kang Byungjin , Park Inho , Ok Changmin , Kim Sungho
Published: December 2021

Recently, hyperspectral image (HSI) classification using deep learning has been actively studied using 2D and 3D convolution neural networks (CNN). However, they learn spatial information as well as spectral information. These methods can increase the accuracy of classification, but do not only focus on the spectral information, which is a big advantage of HSI. In addition, the 1D-CNN, which learns only pure spectral information, has limitations because it uses adjacent spectral information. In this paper, we propose a One Dimensional Parellel Atrous Convolution Neural Network (ODPA-CNN) that learns not only adjacent spectral information for HSI classification, but also spectral information from a certain distance. It extracts features in parallel to account for bands of varying distances. The proposed method excludes spatial information such as the shape of an object and performs HSI classification only with spectral information about the material of the object. Atrous convolution is not a convolution of adjacent spectral information, but a convolution between spectral information separated by a certain distance. We compare the proposed model with various datasets to the other models. We also test with the data we have taken ourselves. Experimental results show a higher performance than some 3D-CNN models and other 1D-CNN methods. In addition, using datasets to which random space is applied, the vulnerabilities of 3D-CNN are identified, and the proposed model is shown to be robust to datasets with little spatial information.
Evolution of Depositional Environments in Response to the Holocene Sea-Level Change in the Lower Delta Plain of Nakdong River Delta, Korea
Authors: Jeong Eun Je , Cheong Daekyo , Kim Jin Cheul , Lim Hyoun Soo , Shin Seungwon
Published: December 2021

The Nakdong River delta, located in southeastern Korea, preserves thick and wide sediments, which are suitable for the high-resolution study of the evolution of depositional environments in the lower delta plain area. This study traces the Holocene evolution of the Nakdong River delta using deep drill core (ND-3; 46.60 m thick) sediments from the present delta plain. Sedimentary units of the sediments were classified based on grain size compositions and sedimentary structures: (A) alluvial zone, (B) estuarine zone, (C) shallow marine, (D) prodelta, (E) delta front, and (F) delta plain. The weathered sediment, paleosol, was observed at 43.16 m below the surface. There is an unconformity (43.10 m) to separate a Pleistocene sediment layer in the lowermost part differentiating from a Holocene sediment layer in the upper part of the core. The shallow marine sedimentary unit (32.20~23.50 m), in which grain size decreases upward is overlain by the prodelta unit (23.50~15.10 m), which consists of fine-grained sediments and relatively homogeneous sedimentary facies. The boundary between the delta front unit (15.10~8.00 m) and the delta plain unit (8.00~0.00 m) appears to lie at 8.0 m, and the variation in grain size is different; coarsening upward in the delta front unit and fining upward in the delta front unit, respectively. These sediments are characterized by a lot of sand–mud couplets and mica flakes aligned along with cross-stratification, which may be deposited in relatively high-energy environments. Until 13 cal ka BP, the sea level was 70 m below the present level and the drilling site might be located onshore. At 10 cal ka BP, the sea level was located 50 m below the present level and the drilling site might be moved to an estuarine environment. From 8 to 6 cal ka BP, a transgression phase occurred as a result of coastline invasion by the rapid rise of the sea level. Thus, the drilling site was drowned in a shallow marine environment. After 6 cal ka BP, the sea level reached the present level, and, since then, progradation might begin to form, primarily by more sediment input. After this period, the progradation phase continues as the sediments have advanced and the delta grows.
A New SEPIC-Based DC-DC Converter with Coupled Inductors Suitable for High Step-Up Applications
Authors: Pop-Calimanu Ioana-Monica , Popescu Sorin , Lascu Dan
Published: December 2021

In this paper, a new hybrid SEPIC dc-dc converter with coupled inductors suitable for photovoltaic applications is presented. First, the way how the new topology was derived will be presented, continuing with its analysis and design equation as a standalone dc-dc topology. The analysis will consist of a steady-state equations derivation, a static conversion ratio calculation based on which the semiconductor voltage and current stresses are evaluated, leading to the continuous conduction mode (CCM) operation conditions. The converter will then be simulated as a first validation of the theory using the dedicated Caspoc power electronics package. To finally validate the theoretical design, a prototype will be built in order to practically demonstrate the feasibility of the proposed solution and to reveal its main practical features and limitations. A comparative study to several other similar topologies will be carried out to identify its most desirable features. Finally, an application of the new hybrid converter will consist of a complete solar energy conversion system using a photovoltaic panel. The maximum power point tracking (MPPT) algorithm will be elaborated. The solar system together with the MPPT will first be modeled, then simulated and practically implemented and tested.
Laboratory Measurements of Zeta Potential in Fractured Lewisian Gneiss: Implications for the Characterization of Flow in Fractured Crystalline Bedrock
Authors: Vinogradov Jan , Hidayat Miftah , Kumar Yogendra , Healy David , Comte Jean-Christophe
Published: December 2021

Despite the broad range of interest and possible applications, the controls on the electric surface charge and the zeta potential of gneiss at conditions relevant to naturally fractured systems remain unreported. There are no published zeta potential measurements conducted in such systems at equilibrium, hence, the effects of composition, concentration and pressure remain unknown. This study reports zeta potential values for the first time measured in a fractured Lewisian gneiss sample saturated with NaCl solutions of various concentrations, artificial seawater and artificial groundwater solutions under equilibrium conditions at confining pressures of 4 MPa and 7 MPa. The constituent minerals of the sample were identified using X-ray diffraction and linked to the concentration and composition dependence of the zeta potential. The results reported in this study demonstrate that the zeta potential remained negative for all tested solutions and concentrations. However, the values of the zeta potential of our Lewisian gneiss sample were found to be unique and dissimilar to pure minerals such as quartz, calcite, mica or feldspar. Moreover, the measured zeta potentials were smaller in magnitude in the experiments with artificial complex solutions compared with those measured with NaCl, thus suggesting that divalent ions (Ca2+, Mg2+ and SO42−) acted as potential determining ions. The zeta potential was also found to be independent of salinity in the NaCl experiments, which is unusual for most reported data. We also investigated the impact of fracture aperture on the electrokinetic response and found that surface electrical conductivity remained negligibly small across the range of the tested confining pressures. Our novel results are an essential first step for interpreting field self-potential (SP) signals and facilitate a way forward for characterization of water flow through fractured basement aquifers.
A Simulation Analysis of an Influenza Vaccine Production Plant in Areas of High Humanitarian Flow. A Preliminary Study for the Region of Norte de Santander (Colombia)
Authors: Contreras-Ropero Jefferson E. , Ruiz-Roa Silvia L. , García-Martínez Janet B. , Urbina-Suarez Néstor A. , López-Barrera Germán L. , Barajas-Solano Andrés F. , Zuorro Antonio
Published: December 2021

The production of vaccines of biological origin presents a tremendous challenge for researchers. In this context, animal cell cultures are an excellent alternative for the isolation and production of biologicals against several viruses, since they have an affinity with viruses and a great capacity for their replicability. Different variables have been studied to know the system’s ideal parameters, allowing it to obtain profitable and competitive products. Consequently, this work focuses its efforts on evaluating an alternative for producing an anti-influenza biological from MDCK cells using SuperPro Designer v8.0 software. The process uses the DMEN culture medium supplemented with nutrients as raw material for cell development; the MDCK cells were obtained from a potential scale-up with a final working volume of 500 L, four days of residence time, inoculum volume of 10%, and continuous working mode with up to a total of 7400 h/Yr of work. The scheme has the necessary equipment for the vaccine’s production, infection, and manufacture with yields of up to 416,698 units/h. In addition, it was estimated to be economically viable to produce recombinant vaccines with competitive prices of up to 0.31 USD/unit.
UAVC: A New Method for Correcting Lidar Overlap Factors Based on Unmanned Aerial Vehicle Vertical Detection
Authors: Zhao Ming , Fang Zhiyuan , Yang Hao , Cheng Liangliang , Chen Jianfeng , Xie Chenbo
Published: December 2021

A method to calibrate the overlap factor of Lidar is proposed, named unmanned aerial vehicle correction (UAVC), which uses unmanned aerial vehicles (UAVs) to detect the vertical distribution of particle concentrations. The conversion relationship between the particulate matter concentration and the aerosol extinction coefficient is inverted by the high-altitude coincidence of the vertical detection profiles of the UAV and Lidar. Using this conversion relationship, the Lidar signal without the influence of the overlap factor can be inverted. Then, the overlap factor profile is obtained by comparing the signal with the original Lidar signal. A 355 nm Raman-Mie Lidar and UAV were used to measure overlap factors under different weather conditions. After comparison with the Raman method, it is found that the overlap factors calculated by the two methods are in good agreement. The changing trend of the extinction coefficient at each height is relatively consistent, after comparing the inversion result of the corrected Lidar signal with the ground data. The results show that after the continuously measured Lidar signal is corrected by the overlap factor measured by this method, low-altitude aerosol information can be effectively obtained.
Hybrid Salp Swarm Algorithm for Solving the Green Scheduling Problem in a Double-Flexible Job Shop
Authors: Liu Changping , Yao Yuanyuan , Zhu Hongbo
Published: December 2021

Green scheduling is not only an effective way to achieve green manufacturing but also an effective way for modern manufacturing enterprises to achieve energy conservation and emission reduction. The double-flexible job shop scheduling problem (DFJSP) considers both machine flexibility and worker flexibility, so it is more suitable for practical production. First, a multi-objective mixed-integer programming model for the DFJSP with the objectives of optimizing the makespan, total worker costs, and total influence of the green production indicators is formulated. Considering the characteristics of the problem, three-layer salp individual encoding and decoding methods are designed for the multi-objective hybrid salp swarm algorithm (MHSSA), which is hybridized with the Lévy flight, the random probability crossover operator, and the mutation operator. In addition, the influence of the parameter setting on the MHSSA in solving the DFJSP is investigated by means of the Taguchi method of design of experiments. The simulation results for benchmark instances show that the MHSSA can effectively solve the proposed problem and is significantly better than the MSSA and the MOPSO algorithm in the diversity, convergence, and dominance of the Pareto frontier.
Reliability Assessment of RC Bridges Subjected to Seismic Loadings
Authors: Herrera Daniel , Varela Gerardo , Tolentino Dante
Published: December 2021

An approach to estimate both the reliability index β and its complement, the probability of failure, through closed-form expressions that consider aleatory and epistemic uncertainties, is proposed. Alternatively, exceedance demand rates are obtained based on simplified expressions and numerical integration. Reliability indicators are calculated, considering the uncertainties in the compressive strength of concrete, steel yield, and section geometry, together with the aleatory uncertainties related to seismic loadings. Such indicators are estimated in a continuous RC bridge located in Acapulco, Guerrero, Mexico. The bridge was designed to comply with a drift of 0.004. Exceedance demand rates for drift thresholds from 0.001 to 0.012 are estimated, and maximum differences of 5.5% are found between the closed-form expression and numerical integration. The exceedance demand rate expressed by means of its inverse, the return period, indicates that the serviceability limit state is exceeded after 58 years of the bridge construction. The reliability index decreases by about 1.66%, and the probability of failure increases by about 16.1% when the epistemic uncertainties are considered. The approach shows the importance of epistemic uncertainties in the estimation of reliability indicators.
The Content and Sources of Potentially Toxic Elements in the Road Dust of Surgut (Russia)
Authors: Moskovchenko Dmitriy , Pozhitkov Roman , Soromotin Andrey , Tyurin Valeriy
Published: December 2021

The chemical and particle size composition of road dust in Surgut, which is a rapidly developing city in Western Siberia, was studied for the first time. Contents of major and trace elements were determined using ICP-MS and ICP-AES, respectively. It was found that the road dust had an alkaline pH (from 7.54 to 9.38) and that the particle size composition was dominated by the 100–250-μm fraction. The contamination assessment based on calculations of the enrichment factor (EF) showed that the road dust was significantly enriched in Sb and Cu and moderately enriched in Zn, Pb, Mo, Ni and W. The sources of these elements are probably associated with the abrasion of car tires and brake pads. Based on calculations of global pollution index (PIr) and total enrichment factor (Ze), the road dust of Surgut was characterized by a generally low level of potential ecological risk, except for stretches of road subject to regular traffic jams, where a moderate ecological risk level was identified. In comparison to the other Russian cities (Moscow, Chelyabinsk, Tyumen, etc.) where studies of road dust composition have been carried out, Surgut had similar contents of Cr and Cu and relatively lower contents of Sb, Cd, As and Pb.
The Space of Functions with Tempered Increments on a Locally Compact and Countable at Infinity Metric Space
Authors: Banaś Józef , Nalepa Rafał
Published: December 2021

The aim of the paper is to introduce the Banach space consisting of real functions defined on a locally compact and countable at infinity metric space and having increments tempered by a modulus of continuity. We are going to provide a condition that is sufficient for the relative compactness in the Banach space in question. A few particular cases of that Banach space will be discussed.
On the Asymptotics and Distribution of Values of the Jacobi Theta Functions and the Estimate of the Type of the Weierstrass Sigma Functions
Authors: Korenkov Mykola , Kharkevych Yurii
Published: December 2021

A refined asymptotics of the Jacobi theta functions and their logarithmic derivatives have been received. The asymptotics of the Nevanlinna characteristics of the indicated functions and the arbitrary elliptic function have been found. The estimation of the type of the Weierstrass sigma functions has been given.
Highly Purified Conjugates of Natural Chlorin with Cobalt Bis(dicarbollide) Nanoclusters for PDT and BNCT Therapy of Cancer
Authors: Fedotova Maria , Usachev Maksim , Bogdanova Ekaterina , Diachkova Ekaterina , Vasil’ev Yuriy , Bregadze Vladimir , Mironov Andrey , Grin Mikhail
Published: December 2021

To combine the neutron-capturing and photodynamic properties of boron nanoclusters and derivatives of natural chlorins, respectively, in one molecule, conjugate of chlorin e6 methyl ester with cyclen and dioxane and nitrile derivatives of cobalt bis(dicarbollide) were synthesized. The conditions for the purification of compounds by HPLC were selected since the work with natural compounds is complicated by the production of closely related impurities.
The Influence of Biomolecule Composition on Colloidal Beer Structure
Authors: Gribkova Irina N. , Eliseev Michail N. , Belkin Yuri D. , Zakharov Maxim A. , Kosareva Olga A.
Published: December 2021

Recent studies have revealed an interest in the composition of beer biomolecules as a colloidal system and their influence on the formation of beer taste. The purpose of this research was to establish biochemical interactions between the biomolecules of plant-based raw materials of beer in order to understand the overall structure of beer as a complex system of bound biomolecules. Generally accepted methods of analytical research in the field of brewing, biochemistry and proteomics were used to solve the research objectives. The studies allowed us to establish the relationship between the grain and plant-based raw materials used, as well as the processing technologies and biomolecular profiles of beer. The qualitative profile of the distribution of protein compounds as a framework for the formation of a colloidal system and the role of carbohydrate dextrins and phenol compounds are given. This article provides information about the presence of biogenic compounds in the structure of beer that positively affect the functioning of the body. A critical assessment of the influence of some parameters on the completeness of beer taste by biomolecules is given. Conclusion: the conducted analytical studies allowed us to confirm the hypothesis about the nitrogen structure of beer and the relationship of other biomolecules with protein substances, and to identify the main factors affecting the distribution of biomolecules by fractions.
Development of Small-Molecule STING Activators for Cancer Immunotherapy
Authors: Jung Hee Ra , Jo Seongman , Jeon Min Jae , Lee Hyelim , Chu Yeonjeong , Lee Jeehee , Kim Eunha , Song Gyu Yong , Jung Cheulhee , Kim Hyejin , Lee Sanghee
Published: December 2021

In cancer immunotherapy, the cyclic GMP–AMP synthase–stimulator of interferon genes (STING) pathway is an attractive target for switching the tumor immunophenotype from ‘cold’ to ‘hot’ through the activation of the type I interferon response. To develop a new chemical entity for STING activator to improve cyclic GMP-AMP (cGAMP)-induced innate immune response, we identified KAS-08 via the structural modification of DW2282, which was previously reported as an anti-cancer agent with an unknown mechanism. Further investigation revealed that direct STING binding or the enhanced phosphorylation of STING and downstream effectors were responsible for DW2282-or KAS-08-mediated STING activity. Furthermore, KAS-08 was validated as an effective STING pathway activator in vitro and in vivo. The synergistic effect of cGAMP-mediated immunity and efficient anti-cancer effects successfully demonstrated the therapeutic potential of KAS-08 for combination therapy in cancer treatment.
VraSR Regulatory System Contributes to the Virulence of Community-Associated Methicillin-Resistant Staphylococcus aureus (CA-MRSA) in a 3D-Skin Model and Skin Infection of Humanized Mouse Model
Authors: Barua Nilakshi , Yang Ying , Huang Lin , Ip Margaret
Published: December 2021

The vancomycin-resistance associated sensor/regulator, VraSR two-component regulatory-system (VraSR), regulates virulence and the response of Staphylococcus aureus (SA) to environmental stress. To investigate the role of VraSR in SA skin and soft tissue infections (SSTI), we inactivated the VraSR of a clinical CA-MRSA ST30 strain by insertional mutation in vraR gene using the TargeTron-Gene Knockout System. We constructed an organotypic keratinocyte fibroblast co-culture (3D-skin model) and a humanized mouse as SSTI infection models. In the 3D-skin model, inactivation of VraSR in the strains ST30 and USA300 showed 1-log reduction in adhesion and internalization (p < 0.001) compared to the respective wildtype. The mutant strains of ST30 (p < 0.05) and USA300-LAC (p < 0.001) also exhibited reduced apoptosis. The wildtype ST30 infection in the humanized mouse model demonstrated increased skin lesion size and bacterial burden compared to BALB/c mice (p < 0.01). The response of the humanized mouse towards the MRSA infection exhibited human similarity indicating that the humanized mouse SSTI model is more suitable for evaluating the role of virulence determinants. Inactivation of VraSR in ST30 strain resulted in decreased skin lesion size in the humanized mouse SSTI model (p < 0.05) and reduction in apoptotic index (p < 0.01) when compared with the wildtype. Our results reveal that inactivating the VraSR system may be a potent anti-virulence approach to control MRSA infection.
A Novel Role of Dapagliflozin in Mitigation of Acetic Acid-Induced Ulcerative Colitis by Modulation of Monocyte Chemoattractant Protein 1 (MCP-1)/Nuclear Factor-Kappa B (NF-κB)/Interleukin-18 (IL-18)
Authors: ElMahdy Mohamed Kh. , Antar Samar A. , Elmahallawy Ehab Kotb , Abdo Walied , Hijazy Hayfa Hussin Ali , Albrakati Ashraf , Khodir Ahmed E.
Published: December 2021

Colon illnesses, particularly ulcerative colitis, are considered a major cause of death in both men and women around the world. The present study investigated the underlying molecular mechanisms for the potential anti-inflammatory effect of Dapagliflozin (DAPA) against ulcerative colitis (UC) induced by intracolonic instillation of 3% v/v acetic acid (AA). DAPA was administered to rats (1 mg/kg, orally) for two weeks during the treatment regimen. Interestingly, compared to the normal group, a marked increase in the index of colon/body weight, colon weight/colon length ratio, serum lactate dehydrogenase (LDH), and C-reactive protein (CRP), besides decrease in the serum total antioxidant capacity (TAC), were reported in the AA control group (p ˂ 0.05). Elevation in colon monocyte chemoattractant protein (MCP1), Interleukin 18 (IL-18), and inflammasome contents were also reported in the AA control group in comparison with the normal group. In addition, colon-specimen immunohistochemical staining revealed increased expression of nuclear factor-kappa B (NF-κB) and Caspase-3 with histopathological changes. Moreover, DAPA significantly (p ˂ 0.05) reduced the colon/body weight index, colon weight/colon length ratio, clinical evaluation, and macroscopic scoring of UC, and preserved the histopathological architecture of tissues. The inflammatory biomarkers, including colon MCP1, IL-18, inflammasome, Caspase-3, and NF-κB, were suppressed following DAPA treatment and oxidants/antioxidants hemostasis was also restored. Collectively, the present data demonstrate that DAPA represents an attractive approach to ameliorating ulcerative colitis through inhibiting MCP1/NF-κB/IL-18 pathways, thus preserving colon function. Antioxidant, anti-inflammatory, and anti-apoptotic properties of DAPA are implicated in its observed therapeutic benefits.
In Vitro Anticancer Activity and Mechanism of Action of an Aziridinyl Galactopyranoside
Authors: Burgos-Morón Estefanía , Pastor Nuria , Orta Manuel Luis , Jiménez-Alonso Julio José , Palo-Nieto Carlos , Vega-Holm Margarita , Vega-Pérez José Manuel , Iglesias-Guerra Fernando , Mateos Santiago , López-Lázaro Miguel , Calderón-Montaño José Manuel
Published: December 2021

We recently screened a series of new aziridines β-D-galactopyranoside derivatives for selective anticancer activity and identified 2-methyl-2,3-[N-(4-methylbenzenesulfonyl)imino]propyl 2,3-di-O-benzyl-4,6-O-(S)-benzylidene-β-D-galactopyranoside (AzGalp) as the most promising compound. In this article, we explore the possible mechanisms involved in the cytotoxicity of this aziridine and evaluate its selective anticancer activity using cancer cells and normal cells from a variety of tissues. Our data show that AzGalp induces DNA damage (comet assay). Cells deficient in the nucleotide excision repair (NER) pathway were hypersensitive to the cytotoxicity of this compound. These results suggest that AzGalp induces bulky DNA adducts, and that cancer cells lacking a functional NER pathway may be particularly vulnerable to the anticancer effects of this aziridine. Several experiments revealed that neither the generation of oxidative stress nor the inhibition of glycolysis played a significant role in the cytotoxicity of AzGalp. Combinations of AzGalp with oxaliplatin or 5-fluorouracil slightly improved the ability of both anticancer drugs to selectively kill cancer cells. AzGalp also showed selective cytotoxicity against a panel of malignant cells versus normal cells; the highest selectivity was observed for two acute promyelocytic leukemia cell lines. Additional preclinical studies are necessary to evaluate the anticancer potential of AzGalp.
Red Cell Distribution Width and Mortality in Patients Undergoing Percutaneous Coronary Intervention
Authors: Liao Min-Tsun , Lai Chao-Lun , Wang Ting-Chuan , Lin Jou-Wei , Ho Yi-Lwun , Chan K. Arnold
Published: December 2021

Red cell distribution width (RDW) can effectively predict prognosis in coronary artery disease (CAD) patients following percutaneous coronary intervention (PCI). There is currently no relevant research to demonstrate a linear or non-linear association between RDW and mortality. This is a multi-center, retrospective cohort study, with data collected from 2006 to 2017. Source data included electronic medical records of the Integrated Medical Database of National Taiwan University Hospital, and health insurance claims from the National Health Insurance Administration. Patients were stratified into five groups according to RDW values (13.4%, 14.1%, 14.8%, and 15.9%). Multivariable logistic and Cox regression analyses were used to determine 1-year all-cause and cardiovascular (CV) mortalities. Data of 10,669 patients were analyzed and those with the lowest RDW (≤13.3%) served as the reference group. The adjusted odds ratios (ORs) of 1-year all-cause mortality from the second to fifth RDW group were 1.386, 1.589, 2.090, and 3.192, respectively (p for trend < 0.001). The adjusted ORs of 1-year CV mortality were 1.555, 1.585, 1.623, and 2.850, respectively (p for trend = 0.015). The adjusted hazard ratios (HRs) of 1-year all-cause mortality were 1.394, 1.592, 2.003, and 2.689, respectively (p for trend = 0.006). The adjusted HRs of 1-year CV mortality were 1.533, 1.568, 1.609, and 2.710, respectively (p for trend = 0.015). RDW was an independent predicting factor and had a linear relationship with the 1-year all-cause and CV mortalities in patients undergoing PCI. Thus, RDW may be a clinically useful parameter to predict the mortality in those patients.
Pathophysiological Mechanisms in Non-Alcoholic Fatty Liver Disease: From Drivers to Targets
Authors: Santos-Laso Alvaro , Gutiérrez-Larrañaga María , Alonso-Peña Marta , Medina Juan M. , Iruzubieta Paula , Arias-Loste María Teresa , López-Hoyos Marcos , Crespo Javier
Published: December 2021

Non-alcoholic fatty liver disease (NAFLD) is characterized by the excessive and detrimental accumulation of liver fat as a result of high-caloric intake and/or cellular and molecular abnormalities. The prevalence of this pathological event is increasing worldwide, and is intimately associated with obesity and type 2 diabetes mellitus, among other comorbidities. To date, only therapeutic strategies based on lifestyle changes have exhibited a beneficial impact on patients with NAFLD, but unfortunately this approach is often difficult to implement, and shows poor long-term adherence. For this reason, great efforts are being made to elucidate and integrate the underlying pathological molecular mechanism, and to identify novel and promising druggable targets for therapy. In this regard, a large number of clinical trials testing different potential compounds have been performed, albeit with no conclusive results yet. Importantly, many other clinical trials are currently underway with results expected in the near future. Here, we summarize the key aspects of NAFLD pathogenesis and therapeutic targets in this frequent disorder, highlighting the most recent advances in the field and future research directions.
Comparative Evaluation of Predicting Energy Consumption of Absorption Heat Pump with Multilayer Shallow Neural Network Training Algorithms
Authors: Kim Jee-Heon , Seong Nam-Chul , Choi Won-Chang
Published: December 2021

The performance of various multilayer neural network algorithms to predict the energy consumption of an absorption chiller in an air conditioning system under the same conditions was compared and evaluated in this study. Each prediction model was created using 12 representative multilayer shallow neural network algorithms. As training data, about a month of actual operation data during the heating period was used, and the predictive performance of 12 algorithms according to the training size was evaluated. The prediction results indicate that the error rates using the measured values are 0.09% minimum, 5.76% maximum, and 1.94 standard deviation (SD) for the Levenberg–Marquardt backpropagation model and 0.41% minimum, 5.05% maximum, and 1.68 SD for the Bayesian regularization backpropagation model. The conjugate gradient with Polak–Ribiére updates backpropagation model yielded lower values than the other two models, with 0.31% minimum, 5.73% maximum, and 1.76 SD. Based on the results for the predictive performance evaluation index, CvRMSE, all other models (conjugate gradient with Fletcher–Reeves updates backpropagation, one-step secant backpropagation, gradient descent with momentum and adaptive learning rate backpropagation, gradient descent with momentum backpropagation) except for the gradient descent backpropagation model yielded results that satisfy ASHRAE (American Society of Heating, Refrigerating and Air-Conditioning Engineers) Guideline 14. The results of this study confirm that the prediction performance may differ for each multilayer neural network training algorithm. Therefore, selecting the appropriate model to fit the characteristics of a specific project is essential.
Orbital Metastases: A Systematic Review of Clinical Characteristics, Management Strategies, and Treatment Outcomes
Authors: Palmisciano Paolo , Ferini Gianluca , Ogasawara Christian , Wahood Waseem , Bin Alamer Othman , Gupta Aditya D. , Scalia Gianluca , Larsen Alexandra M. G. , Yu Kenny , Umana Giuseppe E. , Cohen-Gadol Aaron A. , El Ahmadieh Tarek Y. , Haider Ali S.
Published: December 2021

Background: Orbital metastases often lead to severe functional impairment. The role of resection, orbital exenteration, and complementary treatments is still debated. We systematically reviewed the literature on orbital metastases. Methods: PubMed, Scopus, Web-of-Science, and Cochrane were searched upon PRISMA guidelines to identify studies on orbital metastases. Clinical characteristics, management strategies, and survival were analyzed. Results: We included 262 studies comprising 873 patients. Median age was 59 years. The most frequent primary tumors were breast (36.3%), melanoma (10.1%), and prostate (8.5%) cancers, with median time interval of 12 months (range, 0–420). The most common symptoms were proptosis (52.3%) and relative-afferent-pupillary-defect (38.7%). Most metastases showed a diffuse location within the orbit (19%), with preferential infiltration of orbital soft tissues (40.2%). In 47 cases (5.4%), tumors extended intracranially. Incisional biopsy (63.7%) was preferred over fine-needle aspiration (10.2%), with partial resection (16.6%) preferred over complete (9.5%). Orbital exenteration was pursued in 26 patients (3%). A total of 305 patients (39.4%) received chemotherapy, and 506 (58%) received orbital radiotherapy. Post-treatment symptom improvement was significantly superior after resection (p = 0.005) and orbital radiotherapy (p = 0.032). Mean follow-up was 14.3 months, and median overall survival was 6 months. Fifteen cases (1.7%) demonstrated recurrence with median local control of six months. Overall survival was statistically increased in patients with breast cancer (p < 0.001) and in patients undergoing resection (p = 0.024) but was not correlated with orbital location (p = 0.174), intracranial extension (p = 0.073), biopsy approach (p = 0.344), extent-of-resection (p = 0.429), or orbital exenteration (p = 0.153). Conclusions: Orbital metastases severely impair patient quality of life. Surgical resection safely provides symptom and survival benefit compared to biopsy, while orbital radiotherapy significantly improves symptoms compared to not receiving radiotherapy.
Loss of E-Cadherin Leads to Druggable Vulnerabilities in Sphingolipid Metabolism and Vesicle Trafficking
Authors: Brew Tom , Bougen-Zhukov Nicola , Mitchell Wilson , Decourtye Lyvianne , Schulpen Emily , Nouri Yasmin , Godwin Tanis , Guilford Parry
Published: December 2021

Germline inactivating variants of CDH1 are causative of hereditary diffuse gastric cancer (HDGC), a cancer syndrome characterized by an increased risk of both diffuse gastric cancer and lobular breast cancer. Because loss of function mutations are difficult to target therapeutically, we have taken a synthetic lethal approach to identify targetable vulnerabilities in CDH1-null cells. We have previously observed that CDH1-null MCF10A cells exhibit a reduced rate of endocytosis relative to wildtype MCF10A cells. To determine whether this deficiency is associated with wider vulnerabilities in vesicle trafficking, we screened isogenic MCF10A cell lines with known inhibitors of autophagy, endocytosis, and sphingolipid metabolism. Relative to wildtype MCF10A cells, CDH1−/− MCF10A cells showed significantly greater sensitivity to several drugs targeting these processes, including the autophagy inhibitor chloroquine, the endocytosis inhibitors chlorpromazine and PP1, and the sphingosine kinase 1 inhibitor PF-543. Synthetic lethality was confirmed in both gastric and mammary organoid models of CDH1 loss, derived from CD44-Cre/Cdh1fl/fl/tdTomato mice. Collectively, these results suggest that both sphingolipid metabolism and vesicle trafficking represent previously unrecognised druggable vulnerabilities in CDH1-null cells and may lead to the development of new therapies for HDGC.
Glioblastomas
Authors: Finocchiaro Gaetano , Berzero Giulia
Published: December 2021

Years ago, glioblastoma lost its second name, multiforme, which possibly was an unfortunate decision given the extraordinary heterogeneity of this overly aggressive primary brain tumor, as effectively exemplified by this Latin adjective [...]
A Novel Pd-P Nano-Alloy Supported on Functionalized Silica for Catalytic Aerobic Oxidation of Benzyl Alcohol
Authors: Moeini Seyed Sepehr , Pasqual Laverdura Umberto , Marconi Eleonora , Lisi Nicola , Serra Emanuele , Chierchia Rosa , Luisetto Igor , Tuti Simonetta , Tofani Daniela
Published: December 2021

Catalytic aerobic oxidation of benzyl alcohol (BnOH) to benzaldehyde (PhCHO) over supported noble metal catalysts has grabbed the attention of researchers due to the critical role of PhCHO in numerous industrial syntheses. In the present study, a novel catalyst, Pd-P alloy supported on aminopropyl-functionalized mesoporous silica (NH2-SiO2), was prepared through in situ reduction and characterized by BET-BJH analysis, SEM, TEM, XRD, FTIR, TG-DTA, and XPS. Chemical properties and catalytic performance of Pd-P/NH2-SiO2 were compared with those of Pd° nanoparticles (NPs) deposited on the same support. Over Pd-P/NH2-SiO2, the BnOH conversion to PhCHO was much higher than over Pd°/NH2-SiO2, and significantly influenced by the nature of solvent, reaching 57% in toluene at 111 °C, with 63% selectivity. Using pure oxygen as an oxidant in the same conditions, the BnOH conversion increased up to 78%, with 66% selectivity. The role of phosphorous in improving the activity may consist of the strong interaction with Pd that favours metal dispersion and lowers Pd electron density.
A Rare Mutation in LMNB2 Associated with Lipodystrophy Drives Premature Cell Senescence
Authors: Varlet Alice-Anaïs , Desgrouas Camille , Jebane Cécile , Bonello-Palot Nathalie , Bourgeois Patrice , Levy Nicolas , Helfer Emmanuèle , Dubois Noémie , Valero René , Badens Catherine , Beliard Sophie
Published: December 2021

Many proteins are causative for inherited partial lipodystrophies, including lamins, the essential constituents of the nuclear envelope scaffold called the lamina. By performing high throughput sequencing on a panel of genes involved in lipodystrophies, we identified a heterozygous mutation in LMNB2 gene (c.700C > T p.(Arg234Trp)) in a female patient presenting early onset type II diabetes, hypertriglyceridemia, and android fat distribution. This mutation is rare in the general population (frequency 0.013% in GnomAD) and was predicted pathogenic by a set of pathogenicity prediction software. Patient-derived fibroblasts showed nuclear shape abnormalities and premature senescence features, which are two typical cellular phenotypes associated with laminopathies. Moreover, we observed an atypical aggregation of lamin B2 in nucleoplasm, which co-distributes with emerin and lamin A/C, along with an abnormal distribution of lamin A/C at the nuclear envelope. Finally, reducing lamin B2 expression level by siRNA targeted toward LMNB2 transcripts resulted in decreased nuclear anomalies and senescence-associated beta-galactosidase, suggesting a role of the mutated protein in the occurrence of the observed cellular phenotype. Altogether, these results suggest that mutations in lamin B2 could produce premature senescence and partial lipodystrophy features as observed with certain mutants of lamin A/C.
Bone Marrow Harbors a Unique Population of Dendritic Cells with the Potential to Boost Neutrophil Formation upon Exposure to Fungal Antigen
Authors: Goedhart Marieke , Slot Edith , Pascutti Maria F. , Geerman Sulima , Rademakers Timo , Nota Benjamin , Huveneers Stephan , Buul Jaap D. van , MacNamara Katherine C. , Voermans Carlijn , Nolte Martijn A.
Published: December 2021

Apart from controlling hematopoiesis, the bone marrow (BM) also serves as a secondary lymphoid organ, as it can induce naïve T cell priming by resident dendritic cells (DC). When analyzing DCs in murine BM, we uncovered that they are localized around sinusoids, can (cross)-present antigens, become activated upon intravenous LPS-injection, and for the most part belong to the cDC2 subtype which is associated with Th2/Th17 immunity. Gene-expression profiling revealed that BM-resident DCs are enriched for several c-type lectins, including Dectin-1, which can bind beta-glucans expressed on fungi and yeast. Indeed, DCs in BM were much more efficient in phagocytosis of both yeast-derived zymosan-particles and Aspergillus conidiae than their splenic counterparts, which was highly dependent on Dectin-1. DCs in human BM could also phagocytose zymosan, which was dependent on β1-integrins. Moreover, zymosan-stimulated BM-resident DCs enhanced the differentiation of hematopoietic stem and progenitor cells towards neutrophils, while also boosting the maintenance of these progenitors. Our findings signify an important role for BM DCs as translators between infection and hematopoiesis, particularly in anti-fungal immunity. The ability of BM-resident DCs to boost neutrophil formation is relevant from a clinical perspective and contributes to our understanding of the increased susceptibility for fungal infections following BM damage.
3D Impedimetric Biosensor for Cyanobacteria Detection in Natural Water Sources
Authors: Brosel-Oliu Sergi , Chacón-Aparicio Sandra , Ezenarro Josune Jimenez , Abramova Natalia , Uría Naroa , Bratov Andrey
Published: December 2021

The excessive growth of cyanobacteria in freshwater sources produces the development of toxic blooms mainly due to the production of cyanotoxins. Here, a novel impedimetric biosensor based on a three-dimensional interdigitated electrode array (3D-IDEA) for detection of cyanobacteria cells is reported. The 3D-IDEA sensor surface biofunctionalization was performed by means of the layer-by-layer method using polyethyleneimine (PEI) as the anchoring layer and concanavalin A (Con A) as the bioreceptor to lipopolysaccharides of cyanobacteria cells. The developed PEI-Con A 3D-IDEA sensors show a linear response (R2 = 0.992) of the impedance changes (RS) versus the logarithm of cyanobacteria concentrations in the range of 102–105 cells·mL−1 with the detection limit of 100 cells·mL−1. Moreover, to prevent the interference from components that may be present in real water samples and minimize a possible sample matrix effect, a filtration methodology to recover cyanobacterial cells was developed. The proposed methodology allows 91.2% bacteria recovery, permitting to obtain results similar to controlled assays. The developed system can be used in aquatic environments to detect cyanobacteria and consequently to prevent the formation of blooms and the production of cyanotoxins. Con A can bind to most polysaccharides and so react with other types of bacteria. However, currently, on the market, it is not possible to find specific biorecognition elements for cyanobacteria. Taking into consideration the specificity of samples to be analyzed (natural water resources), it is difficult to expect high concentration of other bacteria. In this sense, the developed methodology may be used as an alarm system to select samples for more thorough and precise laboratory analysis.
Determinants of Gender Disparity in Nutritional Intake among Children in Pakistan: Evidence from PDHS
Authors: Shafiq Awaisra , Hussain Abid , Asif Muhammad , Jameel Arif , Sadiq Saiqa , Kanwel Shahida
Published: December 2021

The purpose of this study is to analyze early age malnutrition on a gender basis in Pakistan. Pakistan Demographic and Health Survey (PDHS) 2012–2013 data related to households’ characteristics that affect the nutrition of children less than 5 years of age are used for the estimation of results. Gender disparity (measured by girl malnourished in household/boy malnourished in a household) is constructed for the measurement of gender disparity in early age child nutrition. After synthesizing the PDHS data set, 2119 observations are used for regression results of gender disparity. Regression results are analyzed at the level of 5% confidence interval otherwise insignificant. egression results for gender disparity show that households in good socioeconomic status, a greater number of household members, a mother’s higher level of education, mother employment, and the male head of the household, causes a decrease in gender disparity in nutrition intake of children.
Paediatric Multiple Sclerosis: A Scoping Review of Patients’ and Parents’ Perspectives
Authors: Luca Maria , Ortega-Castro Nerea , Patti Francesco
Published: December 2021

Dealing with paediatric-onset multiple sclerosis is particularly challenging for the young patients and their families, due to its unpredictable symptoms and uncertain outcome. This review aimed at synthesising the qualitative evidence regarding the perspectives about paediatric-onset multiple sclerosis, as expressed by the patients and/or their parents. A literature search was conducted on PubMed and CINAHL. The advanced multi-field search allowed to perform an abstract/title search in both databases, using keywords, combined through Boolean operators. Additional search strategies were adopted: searching the reference list of the selected papers; searching for key authors in the field. All the relevant papers were thoroughly revised using The Joanna Briggs Institute’s data extraction form for qualitative evidence as a guidance. Eight papers were selected. The analysis of these papers allowed to identify some common issues pertaining paediatric-onset multiple sclerosis: (1) onset of symptoms, (2) diagnostic process, (3) reaction to the diagnosis, (4) management and acceptance of multiple sclerosis. The burden of multiple sclerosis was confirmed. However, the young patients and their parents can adjust to the disease. Both the community and the health care professionals must strive to prevent the families dealing with multiple sclerosis from experiencing solitude and rejection.
Rare Genetic Syndromes and Oral Anomalies: A Review of the Literature and Case Series with a New Classification Proposal
Authors: Salerno Claudia , D’Avola Valeria , Oberti Luca , Almonte Elena , Bazzini Elena Maria , Tartaglia Gianluca Martino , Cagetti Maria Grazia
Published: December 2021

Rare genetic syndromes, conditions with a global average prevalence of 40 cases/100,000 people, are associated with anatomical, physiological, and neurological anomalies that may affect different body districts, including the oral district. So far, no classification of oral abnormalities in rare genetic syndromes is present in the literature. The aim of this narrative review is to analyze literature on rare genetic syndromes affecting dento-oro-maxillofacial structures (teeth, maxillary bones, oral soft tissues, or mixed) and to propose a classification according to the detected oral abnormalities. In addition, five significant cases of rare genetic syndromes are presented. The Scale for the Assessment of Narrative Review Articles (SANRA) was followed for this review. From 674 papers obtained through PubMed search, 351 were selected. Sixty-two rare genetic syndromes involving oral manifestations were found and classified. The proposed classification aims to help the clinician to easily understand which dento-oro-maxillofacial findings might be expected in the presence of each rare genetic syndrome. This immediate framework may both help in the diagnosis of dento-oro-maxillofacial anomalies related to the underlying pathology as well as facilitate the drafting of treatment plans with the involvement of a multidisciplinary team.
Unveiling a Hidden Biomarker of Inflammation and Tumor Progression: The 65 kDa Isoform of MMP-9 New Horizons for Therapy
Authors: Rossano Rocco , Larocca Marilena , Macellaro Margherita , Bilancia Domenico , Riccio Paolo
Published: December 2021

Cancer metastasis is a stage of the disease where therapy is mostly ineffective; hence, the need to find reliable markers of its onset. The metalloproteinase-9 (MMP-9, gelatinase B) in its 82 kDa active form, is a good candidate, but here we show that the correspondent little known 65 kDa active MMP-9 isoform, often misrepresented with the other gelatinase MMP-2, is a more suitable marker. Sera from patients with lung and breast cancer were analyzed by bidimensional zymography to detect the activity of MMP-9 and MMP-2. Enzyme identity was confirmed by comparison with MMP-9 standards and by western blotting. The 65 kDa isoform of MMP-9 is a suitable biomarker to monitor tumor progression from tissue neoplasms to metastatic stage, as its activity begins to appear when disease severity increases and becomes very high in metastasis. Moreover, the 65 kDa MMP-9, which derives from the 82 kDa MMP-9, no longer responds to natural MMP-9 inhibitors. As its activity cannot be controlled, its appearance may warn that the pathological process is becoming irreversible. Identification and inhibition of the enzymes converting the inhibitor-sensitive 82 kDa MMP-9 into the corresponding “wild” 65 kDa MMP-9 may allow to develop therapies capable of blocking metastases.