bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the temporal dynamics of rumen bacterial and fungal communities in yaks (Bos grunniens) from 5 days after birth to adulthood by full-length 16S and 18S rRNA sequencing
Authors: Yang Shuli , Zhang Guangrong , Yuan Zaimei , He Shichun , Wang Rongjiao , Zheng Jieyi , Mao Huaming , Chai Jianmin , Wu Dongwang
Published: June 2023

The rumen of ruminants is inhabited by complex and diverse microorganisms. Young animals are exposed to a variety of microorganisms from their mother and the environment, and a few colonize and survive in their digestive tracts, forming specific microflora as the young animals grow and develop. In this study, we conducted full-length sequencing of bacterial and fungal communities in the rumen of pastured yaks of different ages (from 5  days after birth to adulthood) using amplified sequencing technology. The results showed that the rumen microflora of Zhongdian yaks changed gradually from 5 to 180  days after birth and tended to stabilize at 2  years of age. The rumen of adult yaks was the most suitable for the growth and reproduction of most bacteria. Bactria diversity of the yak rumen increased gradually from 5  days after birth to adulthood. With the growth of yaks, different dominated bacteria were enriched in different groups, but Prevotella remained highly abundant in all groups. The yak rumen at 90  days of age was the most suitable for the growth and reproduction of most fungi, and 90 days of age could be a cut-off point for the distribution of fungal communities. Fungal Thelebolus was the firstly reported in yak rumen and was enriched in the yak rumen of 90  days after birth. The most abundant and balanced fungal genera were found in adult yaks, and most of them were only detected in adult yaks. Our study reported on the rumen bacterial and fungal communities of Zhongdian yaks grazed at different ages and provided insights into the dynamic changes of dominant microflora with yak growth.
Translating conventional wisdom on chicken comb color into automated monitoring of disease-infected chicken using chromaticity-based machine learning models
Authors: Bakar Mohd Anif A. A. , Ker Pin Jern , Tang Shirley G. H. , Baharuddin Mohd Zafri , Lee Hui Jing , Omar Abdul Rahman
Published: June 2023

Bacteria- or virus-infected chicken is conventionally detected by manual observation and confirmed by a laboratory test, which may lead to late detection, significant economic loss, and threaten human health. This paper reports on the development of an innovative technique to detect bacteria- or virus-infected chickens based on the optical chromaticity of the chicken comb. The chromaticity of the infected and healthy chicken comb was extracted and analyzed with International Commission on Illumination (CIE) XYZ color space. Logistic Regression, Support Vector Machines (SVMs), K-Nearest Neighbors (KNN), and Decision Trees have been developed to detect infected chickens using the chromaticity data. Based on the X and Z chromaticity data from the chromaticity analysis, the color of the infected chicken’s comb converged from red to green and yellow to blue. The development of the algorithms shows that Logistic Regression, SVM with Linear and Polynomial kernels performed the best with 95% accuracy, followed by SVM-RBF kernel, and KNN with 93% accuracy, Decision Tree with 90% accuracy, and lastly, SVM-Sigmoidal kernel with 83% accuracy. The iteration of the probability threshold parameter for Logistic Regression models has shown that the model can detect all infected chickens with 100% sensitivity and 95% accuracy at the probability threshold of 0.54. These works have shown that, despite using only the optical chromaticity of the chicken comb as the input data, the developed models (95% accuracy) have performed exceptionally well, compared to other reported results (99.469% accuracy) which utilize more sophisticated input data such as morphological and mobility features. This work has demonstrated a new feature for bacteria- or virus-infected chicken detection and contributes to the development of modern technology in agriculture applications.
Enhancing Heart Disease Prediction through Ensemble Learning Techniques with Hyperparameter Optimization
Authors: Asif Daniyal , Bibi Mairaj , Arif Muhammad Shoaib , Mukheimer Aiman
Published: June 2023

Heart disease is a significant global health issue, contributing to high morbidity and mortality rates. Early and accurate heart disease prediction is crucial for effectively preventing and managing the condition. However, this remains a challenging task to achieve. This study proposes a machine learning model that leverages various preprocessing steps, hyperparameter optimization techniques, and ensemble learning algorithms to predict heart disease. To evaluate the performance of our model, we merged three datasets from Kaggle that have similar features, creating a comprehensive dataset for analysis. By employing the extra tree classifier, normalizing the data, utilizing grid search cross-validation (CV) for hyperparameter optimization, and splitting the dataset with an 80:20 ratio for training and testing, our proposed approach achieved an impressive accuracy of 98.15%. These findings demonstrated the potential of our model for accurately predicting the presence or absence of heart disease. Such accurate predictions could significantly aid in early prevention, detection, and treatment, ultimately reducing the mortality and morbidity associated with heart disease.
Development of an Adaptive Fuzzy Sliding Mode Controller of an Electrohydraulic Actuator Based on a Virtual Prototyping
Authors: Tho Nguyen Huu , Phuong Vo Ngoc Yen , Danh Le Thanh
Published: June 2023

The EHA (electro hydraulic actuator) has a notable advantage over conventional hydraulic actuators as it uses a closed-loop circuit, reducing the size and volume of oil, and eliminates pressure losses caused by valve orifices. However, accurate control performance of EHA is difficult to achieve using a traditional PID (proportional integral derivative) controller due to the strongly nonlinear, time-varying, and unknown dynamics of the system. Hence this paper seeks to address this problem by proposing a design of an intelligent controller for the EHA. The proposed adaptive fuzzy sliding mode controller (AFSMC) is developed as a hybrid of the adaptive, fuzzy logic, and sliding mode algorithms. To reduce costs and time, a virtual prototype approach is also proposed instead of experimentations to evaluate the performance of the proposed controller. The virtual model of the EHA is built in Amesime software, and then embedded into Matlab/Simulink where the AFSMC is developed and tested to obtain the position responses of the EHA. The results show that the AFSMC is highly successful and more efficient than the traditional PID at controlling the position of the piston accurately.
Evaluation of the One Health-Ness of 20 Years of Antimicrobial Resistance Surveillance in Norway
Authors: Norström Madelaine , Simonsen Gunnar Skov , Slettemeås Jannice Schau , Furberg Anne-Sofie , Urdahl Anne Margrete
Published: June 2023

We evaluated the One Health-ness (OH-ness) of the surveillance system for antimicrobial resistance (AMR) in Norway by using the recently developed “Evaluation tool for One Health epidemiological surveillance capacities and capabilities” (OH–EpiCap tool). First, we defined the Norwegian AMR surveillance system that we would evaluate. The tool was applied by a group of stakeholders (key persons in the Norwegian AMR surveillance programmes and authors of this paper). The evaluation was performed using a consensus approach. The evaluation resulted in an overall OH-ness score of 68% across all three dimensions included in the tool: Organisation, Operation, and Impact. Suggestions for improvement were only indicated within the areas of internal evaluation and operational costs, whereas most of the indicators included in the tool showed good adherence to the One Health principles. By performing this internal evaluation, we recognized that AMR surveillance in the environment needs to be included in a more systematic and standardized way to improve the OH-ness as defined by the quadripartite organisations. Last but not least, it was beneficial to bring key stakeholders together to conduct the evaluation. It increased a joint perception of the OH-ness of AMR surveillance in Norway and encouraged further collaboration in the future.
The Effects of Preservatives on Antibiotic- and Preservative-Resistant Microbes and Nitrogen/Sulfur Cycle Associated Microbial Communities in Freshwater River Sediments
Authors: Liao Chien-Sen , Cao Xuan-Di , Lee Wei-Chen , Yang Chu-Wen
Published: June 2023

The intensive use of benzoic acid (BA), 4-hydroxybenzoic acid (HB), and dehydroacetate (DHA) as additives and preservatives in cosmetics and foods causes emerging environmental pollutions. Anthropogenic releases of BA, HB and DHA are primarily emissions into water and soil. However, few studies investigate the effects of BA, HB and DHA on microbial communities in freshwater river sediments. The aim of this study is to reveal the effects of BA, HB and DHA on microbial communities in freshwater river sediments. Tetracycline-, sulfamethoxazole- and preservative-resistant microbes were increased in the river sediments treated with BA, HB and DHA. The relative abundances of methanogen- and xenobiotic-degradation-associated microbial communities were also increased in the BA-, HB- and DHA-treated sediments. The relative abundance of four nitrogen cycle associated microbial groups (anammox, nitrogen fixation, denitrification, and dissimilatory nitrate reduction) were increased after the eighth week in the BA-, HB- and DHA-treated sediments. For the sulfur cycle, the relative abundance of thiosulfate oxidation associated microbial communities were increased after the eighth week in the BA-, HB- and DHA-treated sediments. Results of this study provide insight into the effects of BA, HB and DHA on antibiotic resistance, nitrogen cycle, sulfur cycle, drug resistance and methane production in freshwater aquatic environments.
3-Bromo-4,5-dihydroxybenzaldehyde Protects Keratinocytes from Particulate Matter 2.5-Induced Damages
Authors: Zhen Ao-Xuan , Piao Mei-Jing , Kang Kyoung-Ah , Fernando Pincha-Devage-Sameera-Madushan , Herath Herath-Mudiyanselage-Udari-Lakmini , Cho Suk-Ju , Hyun Jin-Won
Published: June 2023

Cellular senescence can be activated by several stimuli, including ultraviolet radiation and air pollutants. This study aimed to evaluate the protective effect of marine algae compound 3-bromo-4,5-dihydroxybenzaldehyde (3-BDB) on particulate matter 2.5 (PM2.5)-induced skin cell damage in vitro and in vivo. The human HaCaT keratinocyte was pre-treated with 3-BDB and then with PM2.5. PM2.5-induced reactive oxygen species (ROS) generation, lipid peroxidation, mitochondrial dysfunction, DNA damage, cell cycle arrest, apoptotic protein expression, and cellular senescence were measured using confocal microscopy, flow cytometry, and Western blot. The present study exhibited PM2.5-generated ROS, DNA damage, inflammation, and senescence. However, 3-BDB ameliorated PM2.5-induced ROS generation, mitochondria dysfunction, and DNA damage. Furthermore, 3-BDB reversed the PM2.5-induced cell cycle arrest and apoptosis, reduced cellular inflammation, and mitigated cellular senescence in vitro and in vivo. Moreover, the mitogen-activated protein kinase signaling pathway and activator protein 1 activated by PM2.5 were inhibited by 3-BDB. Thus, 3-BDB suppressed skin damage induced by PM2.5.
In Vitro Characterization of Antioxidant, Antibacterial and Antimutagenic Activities of the Green Microalga Ettlia pseudoalveolaris
Authors: Vornoli Andrea , Grande Teresa , Lubrano Valter , Vizzarri Francesco , Gorelli Chiara , Raffaelli Andrea , Croce Clara Maria Della , Baca Santiago Zarate , Sandoval Carla , Longo Vincenzo , Pozzo Luisa , Echeverria Cristina
Published: June 2023

Recently, green microalgae have gained importance due to their nutritional and bioactive compounds, which makes them some of the most promising and innovative functional foods. The aim of this study was to evaluate the chemical profile and the in vitro antioxidant, antimicrobial and antimutagenic activity of an aqueous extract of the green microalga Ettlia pseudoalveolaris, obtained from the freshwater lakes of the Ecuadorian Highlands. Human microvascular endothelial cells (HMEC-1) were used to determine the ability of the microalga to reduce the endothelial damage caused by hydrogen peroxide-induced oxidative stress. Furthermore, the eukaryotic system Saccharomyces cerevisiae was used to evaluate the possible cytotoxic, mutagenic and antimutagenic effect of E. pseudoalveolaris. The extract showed a notable antioxidant capacity and a moderate antibacterial activity mostly due to the high content in polyphenolic compounds. It is likely that the antioxidant compounds present in the extract were also responsible for the observed reduction in endothelial damage of HMEC-1 cells. An antimutagenic effect through a direct antioxidant mechanism was also found. Based on the results of in vitro assays, E. pseudoalveolaris proved to be a good source of bioactive compounds and antioxidant, antibacterial and antimutagenic capacities making it a potential functional food.
Benefits of Natural Antioxidants on Oral Health
Authors: Malcangi Giuseppina , Patano Assunta , Ciocia Anna Maria , Netti Anna , Viapiano Fabio , Palumbo Irene , Trilli Irma , Guglielmo Mariafrancesca , Inchingolo Alessio Danilo , Dipalma Gianna , Inchingolo Francesco , Minetti Elio , Inchingolo Angelo Michele
Published: June 2023

In recent years, special attention has been paid to the correlation between oxidation–reduction mechanisms and human health. The free radicals produced via physiological cellular biochemical processes are major contributors to oxidation phenomena. Their instability is the major cause of cellular damage. Free radical reactive oxygen species containing oxygen are the best-known ones. The body neutralises the harmful effects of free radicals via the production of endogenous antioxidants (superoxide dismutase, catalase, glutathione, and melatonin). The field of study of nutraucetics has found antioxidant capacity in substances such as vitamins A, B, C, E, coenzyme Q-10, selenium, flavonoids, lipoic acid, carotenoids, and lycopene contained in some foods. There are several areas of investigation that aim to research the interaction between reactive oxygen species, exogenous antioxidants, and the microbiota to promote increased protection via the peroxidation of macromolecules (proteins, and lipids) by maintaining a dynamic balance among the species that make up the microbiota. In this scoping review, we aim to map the scientific literature on oxidative stress related to the oral microbiota, and the use of natural antioxidants to counteract it, to assess the volume, nature, characteristics, and type of studies available to date, and to suggest the possible gaps that will emerge from the analysis.
Tyrosine Nitroxidation Does Not Affect the Ability of α-Synuclein to Bind Anionic Micelles, but It Diminishes Its Ability to Bind and Assemble Synaptic-like Vesicles
Authors: Uceda Ana Belén , Frau Juan , Vilanova Bartolomé , Adrover Miquel
Published: June 2023

Parkinson’s disease (PD) is characterized by dopaminergic neuron degeneration and the accumulation of neuronal inclusions known as Lewy bodies, which are formed by aggregated and post-translationally modified α-synuclein (αS). Oxidative modifications such as the formation of 3-nitrotyrosine (3-NT) or di-tyrosine are found in αS deposits, and they could be promoted by the oxidative stress typical of PD brains. Many studies have tried to elucidate the molecular mechanism correlating nitroxidation, αS aggregation, and PD. However, it is unclear how nitroxidation affects the physiological function of αS. To clarify this matter, we synthetized an αS with its Tyr residues replaced by 3-NT. Its study revealed that Tyr nitroxidation had no effect on either the affinity of αS towards anionic micelles nor the overall structure of the micelle-bound αS, which retained its α-helical folding. Nevertheless, we observed that nitroxidation of Y39 lengthened the disordered stretch bridging the two consecutive α-helices. Conversely, the affinity of αS towards synaptic-like vesicles diminished as a result of Tyr nitroxidation. Additionally, we also proved that nitroxidation precluded αS from performing its physiological function as a catalyst of the clustering and the fusion of synaptic vesicles. Our findings represent a step forward towards the completion of the puzzle that must explain the molecular mechanism behind the link between αS-nitroxidation and PD.
Study on Changes in Physical and Mechanical Properties and Integrity Decay of Sandstone Subjected to Freeze–Thaw Cycling
Authors: Wang Liping , Chen Xiaotong , Zhang Wan , Tian Yanzhe , Xu Shuanhai
Published: June 2023

To investigate the effects of long-term freeze–thaw cycles on the physical and mechanical properties as well as the attenuation trend of rocks, this study conducted saturated freeze–thaw tests on coarse sandstone and fine sandstone samples collected from the slopes of Muli Coal Mine in Qinghai Province. The samples underwent different numbers of freeze–thaw cycles, and their porosity, longitudinal wave velocity, and uniaxial compression strength were studied. The variations in the physical and mechanical properties of the two types of sandstone with respect to the number of freeze–thaw cycles were analyzed. Take uniaxial compressive strength (UCS) as the integrity index, and decay laws of rock integrity were analyzed based on the decay equation suggested in previous studies. We found that the decay index λ, which is commonly assumed to be constant, varies with the number of freeze–thaw cycles. Furthermore, the λ values varied between different rock types. For fine sandstone, the λ decreases with an increase in the number of freeze–thaw cycles, ranging from 0.00385 to 0.005. However, for coarse sandstone, the λ initially decreases and then increases with an increase in the number of freeze–thaw cycles. The range of λ for coarse sandstone is between 0.00376 and 0.00481. Finally, we established a relationship between the decay index, porosity, and longitudinal wave velocity in the fine sandstones. This relationship provides a more straightforward way to evaluate the integrity of fine sandstones subjected to different numbers of freeze–thaw cycles.
Evaluation of Dynamic Properties of Trees Subjected to Induced Vibrations
Authors: Grande Ernesto , Giordano Ersilia , Clementi Francesco
Published: June 2023

The preservation of trees in urban and archeological areas is a theme of particular relevance. Modern systems of monitoring, together with approaches for deriving the main characteristics of trees influencing their response toward extreme events, are nowadays at the basis of a growing number of studies. The aim of the present paper is the dynamic identification of trees carried out by employing an approach which combines a simple data-acquisition system, direct and ambient sources of excitation, and different data-processing methods. In particular, using a single accelerometer placed at different sections of the trunk and considering excitations induced by either pulling tests or ambient vibrations, the derivation of the main frequencies and levels of modal damping characterizing the dynamic response of a sour cherry tree (Prunus cerasus) is carried out. A finite element model of the tree is also carried out to support the validation of the proposed approach and further analyze the derived outcomes. The obtained results underline the feasibility of the proposed approach in deriving information useful for assessing the behavior of trees toward dynamic actions and, consequently, of particular relevance for the identification of possible damages induced by variations in terms of dynamic characteristics (frequencies) and damping.
A Decomposition Algorithm for Dynamic Car Sequencing Problems with Buffers
Authors: Zhang Haida , Ding Wensi
Published: June 2023

In this paper, we research the dynamic car sequencing problem with car body buffer (DCSPwB) in automotive mixed-flow assembly. The objective is to reorder the sequence of cars in the paint shop using the post-painted body buffers to minimize the violation of constraint rules and the time cost of sequencing in the general assembly shop. We establish a mathematical model of DCSPwB and propose a decomposition-based algorithm based on the dynamic genetic algorithm (DGA) and greedy algorithm for delayed car release (PGDA). Experiments are conducted based on production orders from actual companies, and the results are compared with the solution results of the underlying genetic algorithm (GA) and greedy algorithm (GDA) to verify the effectiveness of the algorithm. In addition, the effect of buffer capacity on DCSPwB is investigated.
Performance of Solar Hybrid Cooling Operated by Solar Compound Parabolic Collectors under Weather Conditions in Riyadh, Kingdom of Saudi Arabia
Authors: Kaneesamkandi Zakariya , Sayeed Abdul
Published: June 2023

The scientific aim of this work is to encourage energy conservation. This article offers a fresh perspective on renewable energy in the air conditioning sector, the country’s economic growth, and environment-friendly techniques to overcome global warming challenges. In this research, a solar vapor absorption refrigeration (SVAR) system was combined with a conventional vapor compression refrigeration (VCR) system to analyze their combined performance, employing a compound parabolic collector (CPC). The goal was to assess the performance of a solar hybrid cooling system using this non-tracking solar collector. CPC was validated for heat output with 2.9% uncertainty by utilizing an engineering equation solver (EES). Other system components were also validated with EES and then extended to a larger-capacity solar hybrid cooling system. The results of this research indicate that CPC is effective in providing the required heat to SVAR throughout the year without any tracking, and the integration of SVAR in series with the VCR condenser produces 83% higher COP than the system that integrates VCR with the condenser of the SVAR system for Riyadh. The configuration results in high values of exergy COP and an efficiency of 88% and 84%, respectively, increases the cooling capacity of the VCR by 68%, and decreases the carbon emission by 166.4%.
Special Issue: “Research on Biomedical Signal Processing”
Authors: Varanini Maurizio , Tonacci Alessandro , Billeci Lucia
Published: June 2023

Over recent years, the number of signals of a different type that can be acquired from the human body has increased extraordinarily [...]
Manifestation of Heat-Induced Valuable Dietary Nucleotide Salvage in Food Prepared from Aged Fish in Fast Protein and Metabolites Liquid Chromatography, ATP-Bioluminescence Assay, and NMR Spectra
Authors: Sünter Alar , Kuznetsov Artur , Raudsepp Piret , Püssa Tõnu , Toom Lauri , Konoplev Georgii , Stepanova Oksana S. , Stepanova Oksana V. , Lyalin Daniil , Frorip Aleksandr , Roasto Mati
Published: June 2023

Dietary nucleotides and nucleosides, primarily inosine monophosphate (IMP) and the adenine nucleotide pool (ANP), are widely considered as essential nutrients responsible for multiple biological functions. Food prepared from meat and fish is the main source of these substances in the human diet, and it is extremely important to implement storage and processing techniques ensuring their maximum preservation and even accumulation during maturation or conditioning. In experiments with freshly refrigerated grass carp and defrosted Alaska pollock fillets it was discovered, initially using Fast Protein and Metabolites Liquid Chromatography and the ATP-bioluminescence test, and afterwards validated by NMR spectroscopy, that heat treatment identical to conventional culinary processing in aqueous or wet media at temperatures above 62 °C leads to nucleotide salvage (recovery) in aged fish. A significant increase in the concentration of IMP, and even an emergence of ANP substances, were reliably demonstrated in fish samples which had already partially or fully lost these components during prolonged storage due to the ATP breakdown metabolic reactions. Owing to this recovery, the nutritive value of ready-to-eat food can be higher than was initially evaluated in raw products before heat treatment: an effect that should certainly be considered in practical nutrition. Moreover, it is necessary to reconsider the widely acknowledged system of indices of freshness based on nucleotides and nucleosides elaborated a long time ago for raw meat and fish products.
High-Precision and Robust SOC Estimation of LiFePO4 Blade Batteries Based on the BPNN-EKF Algorithm
Authors: Zhang Zhihang , Chen Siliang , Lu Languang , Han Xuebing , Li Yalun , Chen Siqi , Wang Hewu , Lian Yubo , Ouyang Minggao
Published: June 2023

The lithium iron phosphate (LiFePO4) blade battery is a long, rectangular-shaped cell that can be directly integrated into battery pack systems. It enhances volumetric power density, significantly reduces costs, and is widely utilized in electric vehicles. However, the flat open circuit voltage and significant polarization differences under wide operational temperatures are challenging for accurate voltage modeling of battery management systems (BMSs). In particular, inaccurate state of charge (SOC) estimation may cause overcharging and over-discharging risks. To accurately perceive the SOC of LiFePO4 blade batteries, a SOC estimation method based on the backpropagation neural network-extended Kalman filter (BPNN-EKF) algorithm is proposed. BPNN is a neural network model that utilizes the backpropagation algorithm to update model parameters, while EKF is an optimal estimation algorithm. Firstly, dynamic working condition tests, including the New European Driving Cycle (NEDC) and high-speed working (HSW) condition tests, are conducted under a wide temperature range (−25–43 °C). HSW conditions refer to a simulated operating condition that mimics the driving of an electric vehicle on a highway. The minimum voltage of the battery system is used as the output for training the BPNN model. We derive the Kalman gain by combining the BPNN output voltage. Additionally, the EKF algorithm is employed to correct the SOC value using voltage error information. Concerning long SOC calculation intervals, capacity errors, initial SOC errors, and current and voltage sampling errors, the maximum SOC estimation RMSE is 3.98% at −20 °C NEDC, 3.62% at 10 °C NEDC, and 1.68% at 35 °C HSW. The proposed algorithm can be applied to different temperatures and operations, demonstrating high robustness. This BPNN-EKF algorithm has the potential to be embedded in electric vehicle BMS systems for practical applications.
Simulation and Optimization of Lithium-Ion Battery Thermal Management System Integrating Composite Phase Change Material, Flat Heat Pipe and Liquid Cooling
Authors: Xin Qianqian , Yang Tianqi , Zhang Hengyun , Zeng Juan , Xiao Jinsheng
Published: June 2023

A large-capacity prismatic lithium-ion battery thermal management system (BTMS) combining composite phase change material (CPCM), a flat heat pipe (FHP), and liquid cooling is proposed. The three conventional configurations analyzed in this study are the BTMSs using only CPCM, CPCM with aluminum thermal diffusion plates, and CPCM with FHPs. In addition, a CPCM–FHP assisted with liquid cooling at the lateral sides is established to enhance the thermal performance of large-capacity batteries. Moreover, the influences of coolant temperature, the number of FHPs and cooling pipes, and the coolant direction on the temperature field of a BTMS are discussed. Finally, the orthogonal design method is used for the multi-level analysis of multiple factors to improve the light weight of the system. The optimal parameter combination is obtained to achieve the best thermal performance of the BTMS, with the maximum temperature and the temperature difference at 43.17 °C and 3.36 °C, respectively, under a maximum discharge rate of 2C and a high-temperature environment of 37 °C. The optimal scheme is further analyzed and affirmed through the comprehensive balance method.
Risankizumab: Daily Practice Experience of High Need Patients
Authors: Brunasso Alexandra M. G. , Burlando Martina , Amoruso Fabrizio , Arancio Luisa , Malara Giovanna , Manzo Raffaella , Montesu Maria Antonia , Caldarola Giacomo
Published: June 2023

Psoriasis is a chronic inflammatory disease which affects 29.5 million people worldwide and it can negatively impact quality of life, especially when it affects a special localization, such as nails, face, palms and soles, or intertriginous regions. Risankizumab is a humanized monoclonal antibody which targets the p19 subunit of interleukin-23 and it is currently licensed also as systemic therapy for moderate to severe plaque psoriasis. Here, we present eight cases of patients with moderate to severe psoriasis treated with risankizumab with a significant efficacy in the remission of the disease. Our cases represent a real-world clinical setting and provide a valuable adjunct to results obtained in the selected patients usually included in controlled clinical trials. In our cases, risankizumab rapidly improved clinical manifestations and relieved symptoms in patients with moderate to severe psoriasis, regardless of the presence of comorbidities or the location of the plaques in special sites, and without any safety concerns.
The Role of the Microbiome in First Episode of Psychosis
Authors: Nuncio-Mora Lucero , Lanzagorta Nuria , Nicolini Humberto , Sarmiento Emmanuel , Ortiz Galo , Sosa Fernanda , Genis-Mendoza Alma Delia
Published: June 2023

The relationship between the gut-brain-microbiome axis has gained great importance in the study of psychiatric disorders, as it may represent a new target for their treatment. To date, the available literature suggests that the microbiota may influence the pathophysiology of several diseases, including psychosis. The aim of this review is to summarize the clinical and preclinical studies that have evaluated the differences in microbiota as well as the metabolic consequences related to psychosis. Current data suggest that the genera Lactobacillus and Megasphaera are increased in schizophrenia (SZ), as well as alterations in the glutamate-glutamine-GABA cycle, serum levels of tryptophan, kynurenic acid (KYNA), and short-chain fatty acids (SCFAs). There are still very few studies on early-onset psychosis, thus more studies are needed to be able to propose targeted therapies for a point when the disease has just started or has not yet progressed.
Phytochemical Profiling and Anti-Fibrotic Activities of the Gemmotherapy Bud Extract of Corylus avellana in a Model of Liver Fibrosis on Diabetic Mice
Authors: Balta Cornel , Herman Hildegard , Ciceu Alina , Mladin Bianca , Rosu Marcel , Sasu Alciona , Peteu Victor Eduard , Voicu Sorina Nicoleta , Balas Mihaela , Gherghiceanu Mihaela , Dinischiotu Anca , Olah Neli Kinga , Hermenean Anca
Published: June 2023

In this study, we aimed to explore the hepatoprotective effects of the gemmotherapy bud extract of Corylus avellana in a model of liver fibrosis on diabetic mice. An evaluation of total flavonoids and polyphenols contents and LC/MS analyses were performed. Experimental fibrosis was induced with CCl4 (2 mL/kg by i.p. injections twice a week for 7 weeks) in streptozotocin-induced diabetic mice. Our results showed a content of 6–7% flavonoids, while hyperoside and chlorogenic acids were highlighted in the bud extract. Toxic administration of CCl4 increased oxidative stress, mRNA expression of the transforming growth factor-β1 (TGF-β1) and Smad 2/3, and reduced Smad 7 expression. Furthermore, up-regulation of α-smooth muscle actin (α-SMA) revealed an activation of hepatic stellate cells (HSCs), while collagen I (Col I) up-regulation and matrix metalloproteinases (MMPs) unbalance led to an altered extracellular matrix enriched in collagen, confirmed as well by a trichrome stain and electron microscopy analysis. Treatment with gemmotherapy extract significantly restored the liver architecture and the antioxidant balance, and significantly decreased collagen deposits in the liver and improved the liver function. Our results suggest that Corylus avellana gemmotherapy extract may have anti-fibrotic effects and could be useful in the prevention and treatment of liver fibrosis. The hepatoprotective mechanism is based on HSC inhibition, a reduction in oxidative stress and liver damage, a downregulation of the TGF-β1/Smad signaling pathway and a MMPs/TIMP rebalance.
The Effect of Radiotherapy on Cell Survival and Inflammatory Cytokine and Chemokine Secretion in a Co-Culture Model of Head and Neck Squamous Cell Carcinoma and Normal Cells
Authors: Matuszczak Sybilla , Szczepanik Krzysztof , Grządziel Aleksandra , Drzyzga Alina , Cichoń Tomasz , Czapla Justyna , Pilny Ewelina , Smolarczyk Ryszard
Published: June 2023

Radiotherapy (RT) is one of the main treatments for head and neck squamous cell carcinomas (HNSCCs). Unfortunately, radioresistance is observed in many cases of HNSCCs. The effectiveness of RT depends on both the direct effect inducing cell death and the indirect effect of changing the tumor microenvironment (TME). Knowledge of interactions between TME components after RT may help to design a new combined treatment with RT. In the study, we investigated the effect of RT on cell survival and cell secretion in a co-culture model of HNSCCs in vitro. We examined changes in cell proliferation, colony formation, cell cycle phases, type of cell death, cell migration and secretion after irradiation. The obtained results suggest that the presence of fibroblasts and endothelial cells in co-culture with HNSCCs inhibits the function of cell cycle checkpoints G1/S and G2/M and allows cells to enter the next phase of the cell cycle. We showed an anti-apoptotic effect in co-culture of HNSCCs with fibroblasts or endothelial cells in relation to the execution phase of apoptosis, although we initially observed increased activation of the early phase of apoptosis in the co-cultures after irradiation. We hypothesize that the anti-apoptotic effect depends on increased secretion of IL-6 and MCP-1.
Subcutaneous Tocilizumab May Be Effective in Refractory Fibromyalgia Patients
Authors: Tang Kuo-Tung , Liao Tsai-Ling , Chen Yi-Hsing , Chen Der-Yuan , Lai Kou-Lung
Published: June 2023

Introduction: Fibromyalgia (FM) is a chronic disorder characterized by widespread pain with an enormous symptom burden. Its treatment efficacy is limited. Its pathogenesis involves immune dysregulation, which includes interleukin-6 (IL-6) production. Methods: We herein reported a case series of FM patients receiving subcutaneous tocilizumab at our institution. FM symptoms were evaluated by the revised Fibromyalgia Impact Questionnaire (FIQR), which included pain level, and the fibromyalgianess scale based on the 2016 criteria of the American College of Rheumatology (ACR). FM symptoms were compared using the Wilcoxon signed-rank test. Neutrophils from primary FM patients and matched healthy controls were also isolated for transcriptome analysis. Results: We presented a total of two primary and four secondary FM patients who had received subcutaneous tocilizumab for a minimum of 12 weeks. All patients had severe symptoms despite standard treatments. Patients’ FIQR and fibromyalgianess both dropped at 4 and 12 weeks. Four (67%) of them reached a pain reduction of ≥30% at 4 weeks, and three (50%) reached a pain reduction of ≥30% at 12 weeks. Possible differentially expressed genes were identified in primary FM patients when compared with controls and after tocilizumab treatment. Conclusions: FM patients likely benefited from subcutaneous tocilizumab therapy. A randomized controlled trial is needed to verify its efficacy.
Upper Tract Urothelial Carcinoma: A Rare Malignancy with Distinct Immuno-Genomic Features in the Era of Precision-Based Therapies
Authors: Evmorfopoulos Konstantinos , Mitrakas Lampros , Karathanasis Athanasios , Zachos Ioannis , Tzortzis Vassilios , Vlachostergios Panagiotis J.
Published: June 2023

Upper tract urothelial carcinoma (UTUC) is a rare malignancy, occurring in 5–10% of patients diagnosed with UC, and involves the renal pelvis, calyces, or ureters. UTUC can be sporadic or hereditary as a clinical manifestation of Lynch syndrome. Therapeutic management of these patients is challenging. Following risk stratification of localized disease, patients with low-grade UTUC may undergo kidney-sparing surgery or radical nephroureterectomy (RNU) and/or chemoablation with mitomycin-c instillation to reduce recurrence. In high-grade disease, RNU followed by adjuvant chemotherapy remains the standard of care. For decades, platinum-based chemotherapy has been the cornerstone of treatment for locally advanced and metastatic disease. The aim of the present review is to summarize recent advances in UTUC’s therapeutic management through the lens of its genomic and immune landscape. Accumulating knowledge on the genetic and immune aspects of UTUC tumors has increased our understanding of their underlying biology, supporting a luminal papillary, T-cell depleted contexture and enrichment in fibroblast growth factor receptor (FGFR) expression. These advances have fueled successful clinical testing of several precision-based therapeutic approaches, including immune checkpoint inhibitors (ICIs), the antibody–drug conjugates (ADCs) enfortumab vedotin and sacituzumab govitecan, and agents targeting the FGFR axis such as erdafitinib and other kinase inhibitors, allowing their entry into the therapeutic armamentarium and improving the prognosis of these patients. Not all patients respond to these precision-based targeted therapies; thus, validating and expanding the toolkit of potential biomarkers of response or resistance, including molecular subtypes, FGFR pathway gene alterations, DNA repair gene defects, tumor mutational burden (TMB), circulating tumor DNA (ctDNA), nectin-4, TROP2, and programmed death ligand-1 (PD-L1), are key to maximizing the benefit to these particular subgroups of patients.
Relevance of the Updated Recursive Partitioning Analysis (U-RPA) Classification in the Contemporary Care of Patients with Brain Metastases
Authors: Fadul Camilo E. , Sarai Guneet , Bovi Joseph A. , Thomas Alissa A. , Novicoff Wendy , Anderson Roger , Amidon Ryan F. , Schuetz Samantha , Singh Rohit , Chang Amy , Gentzler Ryan D. , Gaughan Elizabeth M. , Sheehan Jason P.
Published: June 2023

Patients with brain metastases (BMETS) need information about the prognosis and potential value of treatment options to make informed therapeutic decisions, but tools to predict survival in contemporary practice are scarce. We propose an Updated Recursive Partitioning Analysis (U-RPA) instrument to predict survival and benefit from brain-directed treatment (BDT) of contemporary patients. This was a retrospective analysis of patients with BMETS treated between 2017 and 2019. With survival as the primary endpoint, we calculated the U-RPA and generated estimates using Kaplan–Meier curves and hazard ratios. Of 862 eligible patients, 752 received BDT and 110 received best supportive care (BSC). Median overall survival with BDT and BSC was 9.3 and 1.3 months, respectively. Patients in RPA class 1, 2A, 2B and 3 who underwent BDT had median survival of 28.1, 14.7, 7.6 and 3.3 months, respectively. The median survival for patients in RPA 3 who received BDT (n = 147), WBRT (n = 79) and SRS (n = 54) was 3.3, 2.9 and 4.1 months, respectively. The U-RPA defines prognosis estimates, independent of tumor type and treatment modality, which can assist to make value-based care treatment decisions. The prognosis for patients in U-RPA class 2B and 3 remains poor, with consideration for early palliative care involvement in these cases.
Potential Correlation between Changes in Serum FGF21 Levels and Lenvatinib-Induced Appetite Loss in Patients with Unresectable Hepatocellular Carcinoma
Authors: Kohya Risako , Suda Goki , Ohara Masatsugu , Sasaki Takashi , Yoda Tomoka , Sakurai Naofumi , Yoshida Sonoe , Fu Qingjie , Yang Zijian , Hosoda Shunichi , Maehara Osamu , Ohnishi Shunsuke , Tokuchi Yoshimasa , Kitagataya Takashi , Suzuki Kazuharu , Kawagishi Naoki , Nakai Masato , Sho Takuya , Natsuizaka Mitsuteru , Ogawa Koji , Sakamoto Naoya
Published: June 2023

Lenvatinib, used for unresectable hepatocellular carcinoma (HCC), causes appetite loss, but the underlying mechanisms, clinical impact, and predictive factors have been unclear. The endocrine factor FGF21 modulates appetite and is involved in cachexia. We evaluated the association between FGF21 level changes during lenvatinib treatment for unresectable HCC and appetite loss. Sixty-three eligible unresectable HCC patients who started lenvatinib treatment between 2018 and 2021 were included. We analyzed FGF21 levels at baseline; 1, 2, and 4 weeks after lenvatinib initiation, and before the onset of appetite loss. Grade ≥ 2 lenvatinib-induced appetite loss led to liver functional reserve deterioration at disease progression and a poor prognosis. Baseline characteristics and serum FGF21 levels were similar between patients with and without appetite loss. However, the serum FGF21 change rate increased significantly at 4 weeks post-lenvatinib initiation in patients with grade ≥ 2 appetite loss, as compared to those without appetite loss. Similar significant increases in the serum FGF21 level change rate were observed prior to grade ≥ 2 appetite loss onset. This suggests that changes in FGF21 levels can be used to predict patients with a greater risk of marked appetite loss and provides insights into the mechanisms underlying lenvatinib-induced appetite loss in patients with HCC.
The Histological Background of Recurrence in Laryngeal Squamous Cell Carcinoma: An Insight into the Modifications of Tumor Microenvironment
Authors: Arcovito Giorgia , Palomba Annarita , Gallo Oreste , Franchi Alessandro
Published: June 2023

Recurrent laryngeal carcinoma presents differences from the primary tumor that largely depend on the treatment. In this article, we review the histologic and molecular treatment-induced changes that may affect the diagnosis of recurrent laryngeal carcinoma, the assessment of predictive markers, and the response to treatment with immune checkpoint inhibitors. Radiotherapy induces profound modifications that are strictly related to necrosis of different tissue components, fibrosis, and damage of the tumor vessels. Postradiotherapy recurrent/persistent laryngeal squamous cell carcinoma typically presents a discohesive growth pattern within a fibrotic background associated with significant changes of the tumor immune microenvironment, with both important immunosuppressive and immunostimulatory effects. Overall, the increase of immunoregulatory cells and immune checkpoints such as CTLA-4, TIM-3, PD-1, and PD-L1 induced by radiotherapy and chemotherapy strongly supports the use of immune checkpoint inhibitors in recurrent/persistent laryngeal carcinoma. Future studies aiming to identify predictive factors of the response to immune checkpoint inhibitors should consider such treatment-induced modifications.
Self-Adaptation of Oxygen Adsorption and Sub-Surface Junction Formation in Thin Nanometric Sheets of Metal Oxides
Authors: Müller Gerhard , Sberveglieri Giorgio
Published: June 2023

Oxygen adsorption at metal oxide (MOX) surfaces and the formation of sub-surface depletion zones in thin nanometric sheets of MOX materials are theoretically investigated. It is shown that—under conditions of sufficient oxygen mobility—the bulk thermal generation of oxygen vacancy donors and the adsorption of surface oxygen ions cooperate in a self-organizing manner to form narrow sub-surface depletion zones which optimally fit into the limited spaces of MOX layers with nanometric cross sections. With this self-organization process in place, both the oxygen adsorption at free surfaces and the bulk generation of oxygen vacancy donors continuously increases as the MOX sheet thickness L is reduced, maintaining at the same time overall electro-neutrality and a state of perfect volume depletion of free carriers in bulk. This process comes to an end when MOX sheet thicknesses of L ≈ 1 nm are approached and when 3d-volumes of about 1 nm3 contain only one single double-donor and two surface oxygen ions on average. It is argued that at this limit of miniaturization, different interpretations of MOX gas sensing phenomena might be required than on larger length scales.
Mobile Dressing Trolleys Improve Satisfaction and Logistics on Pediatric Surgery Wards
Authors: Franck Hannes , Dempfle Astrid , Reischig Katja , Baastrup Jonas , Meinzer Andreas , Kossakowski Meike , Krebs Thomas Franz , Bergholz Robert
Published: June 2023

Background: Evidence-based data on the effect of dressing trolleys on children’s postoperative recovery are not available. The aim of this study was to evaluate a specific pediatric surgical dressing trolley on patient and caregiver satisfaction, as well as temporal and logistical aspects of the dressing change procedures. Methods: In a prospective observational non-randomized study, a total of 100 dressing changes were observed before (group 1) and after (group 2) the introduction of a pediatric surgical dressing trolley and the satisfaction, time and logistical factors were recorded on site. Results: The median preparation time, the duration of the dressing change and the total time decreased significantly from group 1 to group 2 by 1:11 min (p < 0.001); 1:56 min (p = 0.05) and 5:09 min (p = 0.001), respectively. The patient’s room was left significantly less often in group 2 to retrieve missing bandages. The median satisfaction of the medical staff increased by 12% in group 2 (p < 0.001). The satisfaction of the parents increased by 2.5% in group 2 (p = 0.042), and that of the nursing staff increased by 9.25% in group 2 (p = 0.015). Conclusions: Our results demonstrate the positive effects of a dressing trolley for pediatric surgical dressing changes by minimizing postoperative handling and manipulation of the child. It improves time and logistical factors as well as the satisfaction of those involved, which may lead to a faster recovery.
Genomic, Epigenomic, Transcriptomic, Proteomic and Metabolomic Approaches in Atopic Dermatitis
Authors: Bratu Dalia , Boda Daniel , Caruntu Constantin
Published: June 2023

Atopic dermatitis (AD) is a chronic inflammatory skin disease with a high prevalence in the developed countries. It is associated with atopic and non-atopic diseases, and its close correlation with atopic comorbidities has been genetically demonstrated. One of the main roles of genetic studies is to comprehend the defects of the cutaneous barrier due to filaggrin deficit and epidermal spongiosis. Recently, epigenetic studies started to analyze the influence of the environmental factors on gene expression. The epigenome is considered to be a superior second code that controls the genome, which includes alterations of the chromatin. The epigenetic changes do not alter the genetic code, however, changes in the chromatin structure could activate or inhibit the transcription process of certain genes and consequently, the translation process of the new mRNA into a polypeptide chain. In-depth analysis of the transcriptomic, metabolomic and proteomic studies allow to unravel detailed mechanisms that cause AD. The extracellular space and lipid metabolism are associated with AD that is independent of the filaggrin expression. On the other hand, around 45 proteins are considered as the principal components in the atopic skin. Moreover, genetic studies based on the disrupted cutaneous barrier can lead to the development of new treatments targeting the cutaneous barrier or cutaneous inflammation. Unfortunately, at present, there are no target therapies that focus on the epigenetic process of AD. However, in the future, miR-143 could be an important objective for new therapies, as it targets the miR-335:SOX axis, thereby restoring the miR-335 expression, and repairing the cutaneous barrier defects.