bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of the BORUTA Algorithm to Input Data Selection for a Model Based on Rough Set Theory (RST) to Prediction Energy Consumption for Building Heating
Authors: Szul Tomasz , Tabor Sylwester , Pancerz Krzysztof
Published: May 2021

Energy prediction used for building heating has attracted particular attention because it is often required in the development of various strategies to improve the energy efficiency of buildings, especially those undergoing thermal improvements. The complexity, dynamics, uncertainty, and nonlinearity of existing building energy systems create a great need for modeling techniques. One of them is machine learning models, which are based on input data consisting of features that describe the objects under study. The data describing actual buildings used to build the model may be characterized by missing values, duplicate or inconsistent features, noise, and outliers. Therefore, an extremely important aspect of the prediction model development effort is the proper selection of features to simplify the prediction of energy consumption for heating. In this connection, the goal was to evaluate the usefulness of a model describing the final energy demand rate for building heating using groups of features describing actual residential buildings undergoing thermal retrofit. The model was created by combining two algorithms: the BORUTA feature selection algorithm, which prepares conditional variables corresponding to features for a prediction model based on rough set theory (RST). The research was conducted on a group of 109 multi-family buildings from the end of the last century (made in large-panel technology), thermomodernized at the beginning of the 21st century. Evaluation metrics such as MAPE, MBE, CV RMSE, and R2, which are adopted as statistical calibration standards by ASHRAE, were used to assess the quality of the developed prediction model. The analysis of the obtained results indicated that the model based on RST, based on the features selected by the BORUTA algorithm, gives a satisfactory prediction quality with a limited number of input variables, and thus allows to predict energy consumption (after thermal improvement) for this type of buildings with high accuracy.
The Establishment and Evaluation Method of Artificial Microcracks in Rocks
Authors: Wu Zhenkai , Li Xizhe , Xiao Hanmin , Liu Xuewei , Lin Wei , Rao Yuan , Li Yang , Zhang Jie
Published: May 2021

It is necessary to carry out experiments on cores with different degrees of crack development when studying the seepage law of cracked reservoirs and evaluating cracks. The seepage experiment in the laboratory requires cores with different degrees of microcrack development; cores obtained via conventional drilling cannot meet the requirements, and the efficacies and evaluation methods of geological parameters used for artificial cracks are not perfect. In this study, cores are loaded using a triaxial gripper, and cracks are produced by changing the difference of stress; the relationship between the increased rate of permeability and the change in stress concentration is used to evaluate the degree of development of the crack in real time. The angle between the cracks and the maximum principal stress direction, calculated using the Mohr–Coulomb failure criterion, is 20–27.5°, which provides theoretical support for the process of crack creation. The experimental results show that the permeability variation curve shows two obvious turning points, which divide the whole zone into a reduction zone, a slow increase zone, and a rapid increase zone. Through the obtained experimental and evaluation results, a complete system for crack creation and evaluation is established, which can provide strong support for the study of cracked reservoirs.
Determination and Compensation of Non-Active Torques for Parallel HEV Using PMSM/IM Motor(s)
Authors: Dobrucky Branislav , Kascak Slavomir , Frivaldsky Michal , Prazenica Michal
Published: May 2021

The paper deals with the determination and compensation of non-active torques of parallel HEV using an auxiliary electrical PMSM or IM motor. The non-active oscillating torque generating by the ICE engine was estimated, and consequently, the compensating torque component of the current was determined. Based on real measured data, the four regimes of operation have been investigated: compensating non-active torques, parallel operation, regenerating for PMSM, and both parallel operations, together with compensation. Using of p-q theory, the power of fundamental harmonic is presented by average values PAV, QAV of total power waveforms p(t), and q(t). Worked-out simulation results are used for sizing and dimensioning of PMSM machine, VSI inverter, and traction accumulator-battery. Circuit simulator Matlab/Simulink was used for all simulation experiments.
Low-Voltage Electrical Stimulation of Beef Carcasses Slows Carcass Chilling Rate and Improves Steak Color
Authors: Bakker Christina , Underwood Keith , Grubbs Judson Kyle , Blair Amanda
Published: May 2021

Electrical stimulation (ES) is used in beef slaughter plants to improve tenderness; however, varying levels of low-voltage ES have not been well characterized. The objective was to evaluate the influence of two levels of low-voltage ES on temperature decline, pH, glycolytic potential, and meat quality. Forty-two beef carcasses were chosen from a commercial packing facility. One side of each carcass received either 40 or 80 volts of ES for 60 s at 45 min postmortem. The paired side of each carcass did not receive ES (Control). Temperature loggers were placed in the sirloin of 12 carcasses to record temperature decline. Longissimus muscle pH was measured at 1, 12, and 24 h, and 3 d postmortem. Strip steaks were fabricated for determination of meat quality. A treatment by time interaction was observed for carcass temperature decline (p < 0.001) where ES sides stayed warmer longer than Control sides. A treatment by time interaction was observed for pH decline with Control sides exhibiting an increased pH at 1 h postmortem (p < 0.001). Instrumental color values were increased for ES compared to Control sides (p < 0.001). These results indicate ES slows carcass temperature decline, hastens initial pH decline, and improves instrumental color. Similar results were observed between the ES treatments indicating either ES level may be used to achieve similar quality characteristics.
Trends in Sales and Industry Perspectives of Package Sizes of Carbonates and Confectionery Products
Authors: Jensen Chloe , Fang Kirsten , Grech Amanda , Rangan Anna
Published: May 2021

Discretionary food package sizes are an important environmental cue that can affect the amount of food consumed. The aim of this study was to determine sales trends and reported food industry perspectives for changing food package sizes of carbonates and confectionery between 2005 and 2019. Changes in package sizes of carbonates and confectionery were investigated in Australia, the USA, Canada, and the UK. Sales data (units per capita and compound annual growth rate between 2005 and 2019) were extracted from the Euromonitor database. Qualitative data (market research reports) on industry perspectives on package size changes were extracted from industry and marketing databases. Carbonate sales data showed increased growth of smaller package sizes (<300 mL) and a decrease in sales of larger package sizes (≥2000 mL) in all four countries. In contrast, confectionery sales data showed no consistent trends across the selected countries. No growth was observed for smaller confectionery package sizes but an increase in growth of larger package sizes (50–99 g, >100 g), including share packages, was observed in Australia. Qualitative data (n = 92 articles) revealed key reasons identified by industry for changes in package size related to consumer health awareness, portion size control, convenience, market growth, and government or industry initiatives. Monitoring of discretionary food package sizes provides additional insights into consumers’ food environment.
Queue Length Forecasting in Complex Manufacturing Job Shops
Authors: May Marvin Carl , Albers Alexander , Fischer Marc David , Mayerhofer Florian , Schäfer Louis , Lanza Gisela
Published: May 2021

Currently, manufacturing is characterized by increasing complexity both on the technical and organizational levels. Thus, more complex and intelligent production control methods are developed in order to remain competitive and achieve operational excellence. Operations management described early on the influence among target metrics, such as queuing times, queue length, and production speed. However, accurate predictions of queue lengths have long been overlooked as a means to better understanding manufacturing systems. In order to provide queue length forecasts, this paper introduced a methodology to identify queue lengths in retrospect based on transitional data, as well as a comparison of easy-to-deploy machine learning-based queue forecasting models. Forecasting, based on static data sets, as well as time series models can be shown to be successfully applied in an exemplary semiconductor case study. The main findings concluded that accurate queue length prediction, even with minimal available data, is feasible by applying a variety of techniques, which can enable further research and predictions.
The Adenine/Thymine Deleterious Selection Model for GC Content Evolution at the Third Codon Position of the Histone Genes in Drosophila
Authors: Matsuo Yoshinori
Published: May 2021

The evolution of the GC (guanine cytosine) content at the third codon position of the histone genes (H1, H2A, H2B, H3, H4, H2AvD, H3.3A, H3.3B, and H4r) in 12 or more Drosophila species is reviewed. For explaining the evolution of the GC content at the third codon position of the genes, a model assuming selection with a deleterious effect for adenine/thymine and a size effect is presented. The applicability of the model to whole-genome genes is also discussed.
Pillow Support Model with Partitioned Matching Based on Body Pressure Distribution Matrix
Authors: Li Yu , Wu Jianfeng , Lu Chunfu , Tang Zhichuan , Li Chengmin
Published: May 2021

(1) Objective: Sleep problems have become one of the current serious public health issues. The purpose of this research was to construct an ideal pressure distribution model for head and neck support through research on the partitioned support surface of a pillow in order to guide the development of ergonomic pillows. (2) Methods: Seven typical memory foam pillows were selected as samples, and six subjects were recruited to carry out a body pressure distribution experiment. The average value of the first 10% of the samples in the comfort evaluation was calculated to obtain the relative ideal body pressure distribution matrix. Fuzzy clustering was performed on the ideal matrix to obtain the support surface partition. The ideal body pressure index of each partition was calculated, and a hierarchical analysis of each partition was then performed to determine the pressure sensitivity weight of each partition. Using these approaches, the key ergonomic node coordinates of the partitions of four different groups of people were extracted. The ergonomic node coordinates and the physical characteristics of the material were used to design a pillow prototype. Five subjects were recruited for each of the four groups to repeat the body pressure distribution experiment to evaluate the pillow prototype. (3) Results: An ideal support model with seven partitions, including three partitions in the supine position and four partitions in the lateral position, was constructed. The ideal body pressure distribution matrix and ideal body pressure indicators and pressure sensitivity weights for each partition were provided. The pillow that was designed and manufactured based on this model reproduced the ideal pressure distribution matrix evaluated by various groups of people. (4) Conclusion: The seven-partition ideal support model can effectively describe the head and neck support requirements of supine and lateral positions, which can provide strong support for the development of related products.
Implications of a Priori Parameters on Calibration in Conditions of Varying Terrain Characteristics: Case Study of the SAC-SMA Model in Eastern United States
Authors: Chouaib Wafa , Alila Younes , Caldwell Peter V.
Published: May 2021

This study seeks to advance the knowledge about the effect of a priori parameters on calibration using the Sacramento Soil Moisture accounting Model (SAC-SMA). We investigated the catchment characteristics where calibration is most affected by the limitations in the a priori parameters and we studied the effect on the modeled processes. The a priori parameters of SAC-SMA model parameters were determined from soil-derived physical expressions that make use of the soil’s physical properties. The study employed 63 catchments from the eastern United States (US). The model calibration employed the Shuffle-Complex algorithm (SCE-UA) and used the a priori parameters as default allowing for ±35% as a range of deviation. The model efficiency after calibration was sensitive to the catchment landscape properties, particularly the soil texture and topography. The highest efficiency was obtained in conditions of well-drained soils and flat topography where the saturation excess overland flow is predominant. Most of the catchments with smaller efficiency had poorly drained soils where mountainous and forested catchments of predominant subsurface stormflow had the lowest efficiency. The current regional study shows that improvements of SAC-SMA a priori parameters are crucial to foster their operational use for calibration and prediction at ungauged catchments.
Correlation between Elderly Migrants’ Needs and Environmental Adaptability: A Discussion Based on Human Urbanization Features
Authors: Hua Yi , Qiu Zhi , Luo Wenjing , Wang Yue , Wang Zhu
Published: May 2021

Building concentrated resettlement community in small towns is mostly used to deal with resettlement construction for rural migrants in economically developed regions in China, which leads to migrants’ living environment changing from rural settlements where production and living are intertwined to an urban community that only supports living functions. However, the urbanized environment is contrary to elderly migrants’ behavior, resulting in contradictions or conflicts between migrants and resettlement communities, reflecting a lack of urbanization synchronization between migrants and resettlement community environments. Further, elderly migrants are also equipped with different degrees and types of urbanization characteristics, thus reflecting different abilities to adapt to the urban community environment. Based on the corresponding relationship between people’s different production and living needs and urbanization, this research starts by investigating the production and living needs of elderly migrants, and further clarifies the environmental adaptability of elderly migrants by sorting the types and characteristics of urbanization of elderly migrants to provide a reference basis for the planning and construction of future resettlement areas. The research uses questionnaires and semi-structured interviews to investigate the population attributes and characteristics of elderly migrants, as well as their different needs for production and living. The research uses hierarchical cluster analysis, the one-way ANOVA test and Chi-square test to constructed a four-quadrant model on human urbanization features: an Urban Group with both living and production urbanized (Group H-H); a Half-urban-half-rural Group with only living needs urbanized (Group H-L); a Half-urban-Half-rural Group with only production needs urbanized (Group L-H); and a Rural group with both living and production needs not urbanized (Group L-L). Finally, based on the results, this research proposed three elderly environment construction orientations of “Promote the Supply Level of Urban Public Services”, “Create a Place That Embodies the Spirit of Immigrants’ Homeland”, and “Moderate Consideration of Agricultural Production Needs” for residential planning.
An Automatic and Operational Method for Land Cover Change Detection Using Spatiotemporal Analysis of MODIS Data: A Northern Ontario (Canada) Case Study
Authors: Ituen Ima , Hu Baoxin
Published: May 2021

Mapping and understanding the differences in land cover and land use over time is an essential component of decision-making in sectors such as resource management, urban planning, and forest fire management, as well as in tracking of the impacts of climate change. Existing methods sometimes pose a barrier to the effective monitoring of changes in land cover and land use, since a threshold parameter is often needed and determined based on trial and error. This study aimed to develop an automatic and operational method for change detection on a large scale from Moderate Resolution Imaging Spectroradiometer (MODIS) data. Super pixels were the basic unit of analysis instead of traditional individual pixels. T2 tests based on the feature vectors of temporal Normalized Difference Vegetation Index (NDVI) and land surface temperature were used for change detection. The developed method was applied to data over a predominantly vegetated area in northern Ontario, Canada spanning 120,000 sq. km from 2001–2016. The accuracies ranged between 78% and 88% for the NDVI-based test, from 74% to 86% for the LST-based test, and from 70% to 86% for the joint method compared with manual interpretation. Our proposed method for detecting land cover change provides a functional and viable alternative to existing methods of land cover change detection as it is reliable, repeatable, and free from uncertainty in establishing a threshold for change.
Deep Sequencing of Small RNA Reveals the Molecular Regulatory Network of AtENO2 Regulating Seed Germination
Authors: Wu Yu , Zheng Lamei , Bing Jie , Liu Huimin , Zhang Genfa
Published: May 2021

Seed germination is a key step in the new life cycle of plants. In agriculture, we regard the rapid and consistent process of seed germination as one of the necessary conditions to measure the high quality and yield of crops. ENO2 is a key enzyme in glycolysis, which also plays an important role in plant growth and abiotic stress responses. In our study, we found that the time of seed germination in AtENO2 mutation (eno2−) was earlier than that of wild type (WT) in Arabidopsis thaliana. Previous studies have shown that microRNAs (miRNAs) were vital in seed germination. After deep sequencing of small RNA, we found 590 differentially expressed miRNAs in total, of which 87 were significantly differentially expressed miRNAs. By predicting the target genes of miRNAs and analyzing the GO annotation, we have counted 18 genes related to seed germination, including ARF family, TIR1, INVC, RR19, TUDOR2, GA3OX2, PXMT1, and TGA1. MiR9736-z, miR5059-z, ath-miR167a-5p, ath-miR167b, ath-miR5665, ath-miR866-3p, miR10186-z, miR8165-z, ath-miR857, ath-miR399b, ath-miR399c-3p, miR399-y, miR163-z, ath-miR393a-5p, and ath-miR393b-5p are the key miRNAs regulating seed germination-related genes. Through KEGG enrichment analysis, we found that phytohormone signal transduction pathways were significantly enriched, and these miRNAs mentioned above also participate in the regulation of the genes in plant hormone signal transduction pathways, thus affecting the synthesis of plant hormones and further affecting the process of seed germination. This study laid the foundation for further exploration of the AtENO2 regulation for seed germination.
The Potential Role of Flavonoids in Ameliorating Diabetic Cardiomyopathy via Alleviation of Cardiac Oxidative Stress, Inflammation and Apoptosis
Authors: Jubaidi Fatin Farhana , Zainalabidin Satirah , Taib Izatus Shima , Hamid Zariyantey Abd , Budin Siti Balkis
Published: May 2021

Diabetic cardiomyopathy is one of the major mortality risk factors among diabetic patients worldwide. It has been established that most of the cardiac structural and functional alterations in the diabetic cardiomyopathy condition resulted from the hyperglycemia-induced persistent oxidative stress in the heart, resulting in the maladaptive responses of inflammation and apoptosis. Flavonoids, the most abundant phytochemical in plants, have been reported to exhibit diverse therapeutic potential in medicine and other biological activities. Flavonoids have been widely studied for their effects in protecting the heart against diabetes-induced cardiomyopathy. The potential of flavonoids in alleviating diabetic cardiomyopathy is mainly related with their remedial actions as anti-hyperglycemic, antioxidant, anti-inflammatory, and anti-apoptotic agents. In this review, we summarize the latest findings of flavonoid treatments on diabetic cardiomyopathy as well as elucidating the mechanisms involved.
Exposure to 2.45 GHz Radiation Triggers Changes in HSP-70, Glucocorticoid Receptors and GFAP Biomarkers in Rat Brain
Authors: Othman Haifa , López-Furelos Alberto , Leiro-Vidal José Manuel , Ammari Mohamed , Sakly Mohsen , Abdelmelek Hafedh , Salas-Sánchez Aarón Ángel , Ares-Pena Francisco , López-Martín Elena
Published: May 2021

Brain tissue may be especially sensitive to electromagnetic phenomena provoking signs of neural stress in cerebral activity. Fifty-four adult female Sprague-Dawley rats underwent ELISA and immunohistochemistry testing of four relevant anatomical areas of the cerebrum to measure biomarkers indicating induction of heat shock protein 70 (HSP-70), glucocorticoid receptors (GCR) or glial fibrillary acidic protein (GFAP) after single or repeated exposure to 2.45 GHz radiation in the experimental set-up. Neither radiation regime caused tissue heating, so thermal effects can be ruled out. A progressive decrease in GCR and HSP-70 was observed after acute or repeated irradiation in the somatosensory cortex, hypothalamus and hippocampus. In the limbic cortex; however, values for both biomarkers were significantly higher after repeated exposure to irradiation when compared to control animals. GFAP values in brain tissue after irradiation were not significantly different or were even lower than those of nonirradiated animals in all brain regions studied. Our results suggest that repeated exposure to 2.45 GHz elicited GCR/HSP-70 dysregulation in the brain, triggering a state of stress that could decrease tissue anti-inflammatory action without favoring glial proliferation and make the nervous system more vulnerable.
Some Dietary Phenolic Compounds Can Activate Thyroid Peroxidase and Inhibit Lipoxygenase-Preliminary Study in the Model Systems
Authors: Habza-Kowalska Ewa , Kaczor Agnieszka A. , Bartuzi Damian , Piłat Jacek , Gawlik-Dziki Urszula
Published: May 2021

The presented research concerns the triple activity of trans-cinnamic (tCA), ferulic (FA) and syringic acids (SA). They act as thyroid peroxidase (TPO) activators, lipoxygenase (LOX) inhibitors and show antiradical activity. All compounds showed a dose-dependent TPO activatory effect, thus the AC50 value (the concentration resulting in 50% activation) was determined. The tested compounds can be ranked as follows: tCA > FA > SA with AC50 = 0.10, 0.39, 0.69 mM, respectively. Strong synergism was found between FA and SA. The activatory effects of all tested compounds may result from interaction with the TPO allosteric site. It was proposed that conformational change resulting from activator binding to TPO allosteric pocket results from the flexibility of a nearby loop formed by residues Val352-Tyr363. All compounds act as uncompetitive LOX inhibitors. The most effective were tCA and SA, whereas the weakest was FA (IC50 = 0.009 mM and IC50 0.027 mM, respectively). In all cases, an interaction between the inhibitors carboxylic groups and side-chain atoms of Arg102 and Arg139 in an allosteric pocket of LOX was suggested. FA/tCA and FA/SA acted synergistically, whereas tCA/SA demonstrated antagonism. The highest antiradical activity was found in the case of SA (IC50 = 0.22 mM). FA/tCA and tCA/SA acted synergistically, whereas antagonism was found for the SA/FA mixture.
Biology of the mRNA Splicing Machinery and Its Dysregulation in Cancer Providing Therapeutic Opportunities
Authors: Blijlevens Maxime , Li Jing , van Beusechem Victor W.
Published: May 2021

Dysregulation of messenger RNA (mRNA) processing—in particular mRNA splicing—is a hallmark of cancer. Compared to normal cells, cancer cells frequently present aberrant mRNA splicing, which promotes cancer progression and treatment resistance. This hallmark provides opportunities for developing new targeted cancer treatments. Splicing of precursor mRNA into mature mRNA is executed by a dynamic complex of proteins and small RNAs called the spliceosome. Spliceosomes are part of the supraspliceosome, a macromolecular structure where all co-transcriptional mRNA processing activities in the cell nucleus are coordinated. Here we review the biology of the mRNA splicing machinery in the context of other mRNA processing activities in the supraspliceosome and present current knowledge of its dysregulation in lung cancer. In addition, we review investigations to discover therapeutic targets in the spliceosome and give an overview of inhibitors and modulators of the mRNA splicing process identified so far. Together, this provides insight into the value of targeting the spliceosome as a possible new treatment for lung cancer.
Implications of Extended Inhibitory Neuron Development
Authors: Kim Jae-Yeon , Paredes Mercedes F.
Published: May 2021

A prolonged developmental timeline for GABA (γ-aminobutyric acid)-expressing inhibitory neurons (GABAergic interneurons) is an amplified trait in larger, gyrencephalic animals. In several species, the generation, migration, and maturation of interneurons take place over several months, in some cases persisting after birth. The late integration of GABAergic interneurons occurs in a region-specific pattern, especially during the early postnatal period. These changes can contribute to the formation of functional connectivity and plasticity, especially in the cortical regions responsible for higher cognitive tasks. In this review, we discuss GABAergic interneuron development in the late gestational and postnatal forebrain. We propose the protracted development of interneurons at each stage (neurogenesis, neuronal migration, and network integration), as a mechanism for increased complexity and cognitive flexibility in larger, gyrencephalic brains. This developmental feature of interneurons also provides an avenue for environmental influences to shape neural circuit formation.
Transient Global Ischemia-Induced Brain Inflammatory Cascades Attenuated by Targeted Temperature Management
Authors: Hong Dae Ki , Park Yoo Seok , Woo Ji Sun , Kim Ju Hee , Beom Jin Ho , Chung Sung Phil , You Je Sung , Suh Sang Won
Published: May 2021

Sudden cardiac arrest leads to a significantly increased risk of severe neurological impairment and higher mortality rates in survivors due to global brain tissue injury caused by prolonged whole-body ischemia and reperfusion. The brain undergoes various deleterious cascading events. Among these damaging mechanisms, neuroinflammation plays an especially crucial role in the exacerbation of brain damage. Clinical guidelines indicate that 33 °C and 36 °C are both beneficial for targeted temperature management (TTM) after cardiac arrest. To clarify the mechanistic relationship between TTM and inflammation in transient global ischemia (TGI) and determine whether 36 °C produces a neuroprotective effect comparable to 33 °C, we performed an experiment using a rat model. We found that TTM at 36 °C and at 33 °C attenuated neuronal cell death and apoptosis, with significant improvements in behavioral function that lasted for up to 72 h. TTM at 33 °C and 36 °C suppressed the propagation of inflammation including the release of high mobility group box 1 from damaged cells, the activation and polarization of the microglia, and the excessive release of activated microglia-induced inflammatory cytokines. There were equal neuroprotective effects for TTM at 36 °C and 33 °C. In addition, hypothermic complications and should be considered safe and effective after cardiac arrest.
Involvement of Huntingtin in Development and Ciliary Beating Regulation of Larvae of the Sea Urchin, Hemicentrotus pulcherrimus
Authors: Katow Hideki , Katow Tomoko , Yoshida Hiromi , Kiyomoto Masato
Published: May 2021

The multiple functions of the wild type Huntington’s disease protein of the sea urchin Hemicentrotus pulcherrimus (Hp-Htt) have been examined using the anti-Hp-Htt antibody (Ab) raised against synthetic oligopeptides. According to immunoblotting, Hp-Htt was detected as a single band at around the 350 kDa region at the swimming blastula stage to the prism larva stage. From the 2-arm pluteus stage (2aPL), however, an additional smaller band at the 165 kDa region appeared. Immunohistochemically, Hp-Htt was detected in the nuclei and the nearby cytoplasm of the ectodermal cells from the swimming blastula stage, and the blastocoelar cells from the mid-gastrula stage. The Ab-positive signal was converged to the ciliary band-associated strand (CBAS). There, it was accompanied by several CBAS-marker proteins in the cytoplasm, such as glutamate decarboxylase. Application of Hp-Htt morpholino (Hp-Htt-MO) has resulted in shortened larval arms, accompanied by decreased 5-bromo-2-deoxyuridin (BrdU) incorporation by the ectodermal cells of the larval arms. Hp-Htt-MO also resulted in lowered ciliary beating activity, accompanied by a disordered swirling pattern formation around the body. These Hp-Htt-MO-induced deficiencies took place after the onset of CBAS system formation at the larval arms. Thus, Hp-Htt is involved in cell proliferation and the ciliary beating pattern regulation signaling system in pluteus larvae.
Chronic Low-Dose Alcohol Consumption Attenuates Post-Ischemic Inflammation via PPARγ in Mice
Authors: Li Chun , Li Jiyu , Loreno Ethyn G. , Miriyala Sumitra , Panchatcharam Manikandan , Lu Xiaohong , Sun Hong
Published: May 2021

Ischemic stroke is one of the leading causes of death and permanent disability in adults. Recently, we found that light alcohol consumption (LAC) suppresses post-ischemic inflammatory response, which plays an important role in ischemic brain damage. Our goal was to determine the role of peroxisome proliferator-activated receptor-gamma (PPARγ) in the anti-inflammatory effect of LAC against transient focal cerebral ischemia. In in vivo study, male C57BL/6J wild type (WT) and endothelial-specific conditional PPARγ knockout mice were gavage fed with 0.7 g/kg/day ethanol or volume-matched water daily for 8 weeks. From the 7th week, 3 mg/kg/day GW9662 (a selective PPARγ antagonist) was intraperitoneally given for two weeks. Cerebral ischemia/reperfusion (I/R) injury and expression of manganese superoxide dismutase (MnSOD) and adhesion molecules, neutrophil infiltration, and microglial activation in the cerebral cortex before and following a 90 min unilateral middle cerebral artery occlusion (MCAO)/24 h reperfusion were evaluated. In in vitro study, the impact of chronic alcohol exposure on expression of PPARγ and MnSOD in C57BL/6J mouse brain microvascular endothelial cells (MBMVECs) was measured. PPARγ and MnSOD were significantly upregulated in the cerebral cortex of ethanol-fed WT mice and low-concentration ethanol-exposed C57BL/6J MBMVECs. GW9662 significantly inhibited alcohol-induced upregulation of MnSOD. Eight-week ethanol feeding significantly reduced cerebral I/R injury and alleviated the post-ischemic inflammatory response (upregulation of intercellular adhesion molecule-1 (ICAM-1) and E-selectin, microglial activation, and neutrophil infiltration). Treatment with GW9662 and endothelial-specific conditional knockout of PPARγ did not alter cerebral I/R injury and the inflammatory response in the control mice but abolish the neuroprotective effect in ethanol-fed mice. In addition, GW9662 and endothelial-specific conditional knockout of PPARγ diminished the inhibitory effect of LAC on the post-ischemic expression of adhesion molecules and neutrophil infiltration. Our findings suggest that LAC may protect against cerebral I/R injury by suppressing the post-ischemic inflammation via activation of PPARγ.
Alternative C3 Complement System: Lipids and Atherosclerosis
Authors: Garcia-Arguinzonis Maisa , Diaz-Riera Elisa , Peña Esther , Escate Rafael , Juan-Babot Oriol , Mata Pedro , Badimon Lina , Padro Teresa
Published: May 2021

Familial hypercholesterolemia (FH) is increasingly associated with inflammation, a phenotype that persists despite treatment with lipid lowering therapies. The alternative C3 complement system (C3), as a key inflammatory mediator, seems to be involved in the atherosclerotic process; however, the relationship between C3 and lipids during plaque progression remains unknown. The aim of the study was to investigate by a systems biology approach the role of C3 in relation to lipoprotein levels during atherosclerosis (AT) progression and to gain a better understanding on the effects of C3 products on the phenotype and function of human lipid-loaded vascular smooth muscle cells (VSMCs). By mass spectrometry and differential proteomics, we found the extracellular matrix (ECM) of human aortas to be enriched in active components of the C3 complement system, with a significantly different proteomic signature in AT segments. Thus, C3 products were more abundant in AT-ECM than in macroscopically normal segments. Furthermore, circulating C3 levels were significantly elevated in FH patients with subclinical coronary AT, evidenced by computed tomographic angiography. However, no correlation was identified between circulating C3 levels and the increase in plaque burden, indicating a local regulation of the C3 in AT arteries. In cell culture studies of human VSMCs, we evidenced the expression of C3, C3aR (anaphylatoxin receptor) and the integrin αMβ2 receptor for C3b/iC3b (RT-PCR and Western blot). C3mRNA was up-regulated in lipid-loaded human VSMCs, and C3 protein significantly increased in cell culture supernatants, indicating that the C3 products in the AT-ECM have a local vessel-wall niche. Interestingly, C3a and iC3b (C3 active fragments) have functional effects on VSMCs, significantly reversing the inhibition of VSMC migration induced by aggregated LDL and stimulating cell spreading, organization of F-actin stress fibers and attachment during the adhesion of lipid-loaded human VSMCs. This study, by using a systems biology approach, identified molecular processes involving the C3 complement system in vascular remodeling and in the progression of advanced human atherosclerotic lesions.
PD-1/PD-L1 in Cancer: Pathophysiological, Diagnostic and Therapeutic Aspects
Authors: Munari Enrico , Mariotti Francesca R. , Quatrini Linda , Bertoglio Pietro , Tumino Nicola , Vacca Paola , Eccher Albino , Ciompi Francesco , Brunelli Matteo , Martignoni Guido , Bogina Giuseppe , Moretta Lorenzo
Published: May 2021

Immune evasion is a key strategy adopted by tumor cells to escape the immune system while promoting their survival and metastatic spreading. Indeed, several mechanisms have been developed by tumors to inhibit immune responses. PD-1 is a cell surface inhibitory receptor, which plays a major physiological role in the maintenance of peripheral tolerance. In pathological conditions, activation of the PD-1/PD-Ls signaling pathway may block immune cell activation, a mechanism exploited by tumor cells to evade the antitumor immune control. Targeting the PD-1/PD-L1 axis has represented a major breakthrough in cancer treatment. Indeed, the success of PD-1 blockade immunotherapies represents an unprecedented success in the treatment of different cancer types. To improve the therapeutic efficacy, a deeper understanding of the mechanisms regulating PD-1 expression and signaling in the tumor context is required. We provide an overview of the current knowledge of PD-1 expression on both tumor-infiltrating T and NK cells, summarizing the recent evidence on the stimuli regulating its expression. We also highlight perspectives and limitations of the role of PD-L1 expression as a predictive marker, discuss well-established and novel potential approaches to improve patient selection and clinical outcome and summarize current indications for anti-PD1/PD-L1 immunotherapy.
Combined Cardiac Risk Factors Predict COVID-19 Related Mortality and the Need for Mechanical Ventilation in Coptic Clergy
Authors: Henein Michael Y. , Bytyçi Ibadete , Nicoll Rachel , Shenouda Rafik , Ayad Sherif , Cameli Matteo , Vancheri Federico
Published: May 2021

Background and Aims: The clinical adverse events of COVID-19 among clergy worldwide have been found to be higher than among ordinary communities, probably because of the nature of their work. The aim of this study was to assess the impact of cardiac risk factors on COVID-19-related mortality and the need for mechanical ventilation in Coptic clergy. Methods: Of 1570 Coptic clergy participating in the COVID-19-Clergy study, serving in Egypt, USA and Europe, 213 had the infection and were included in this analysis. Based on the presence of systemic arterial hypertension (AH), participants were divided into two groups: Group-I, clergy with AH (n = 77) and Group-II, without AH (n = 136). Participants’ demographic indices, cardiovascular risk factors, COVID-19 management details and related mortality were assessed. Results: Clergy with AH were older (p < 0.001), more obese (p = 0.04), had frequent type 2 diabetes (DM) (p = 0.001), dyslipidemia (p = 0.001) and coronary heart disease (CHD) (p = 0.04) compared to those without AH. COVID-19 treatment at home, hospital or in intensive care did not differ between the patient groups (p > 0.05 for all). Clergy serving in Northern and Southern Egypt had a higher mortality rate compared to those from Europe and the USA combined (5.22%, 6.38%, 0%; p = 0.001). The impact of AH on mortality was significant only in Southern Egypt (10% vs. 3.7%; p = 0.01) but not in Northern Egypt (4.88% vs. 5.81%; p = 0.43). In multivariate analysis, CHD OR 1.607 ((0.982 to 3.051); p = 0.02) and obesity, OR 3.403 ((1.902 to 4.694); p = 0.04) predicted COVID-19 related mortality. A model combining cardiac risk factors (systolic blood pressure (SBP) ≥ 160 mmHg, DM, obesity and history of CHD) was the most powerful independent predictor of COVID-19-related mortality, OR 3.991 ((1.919 to 6.844); p = 0.002). Almost the same model also proved the best independent multivariate predictor of mechanical ventilation OR 1.501 ((0.809 to 6.108); p = 0.001). Conclusion: In Coptic clergy, the cumulative impact of risk factors was the most powerful predictor of mortality and the need for mechanical ventilation.
Carbapenem-Resistant Klebsiella pneumoniae Infections in ICU COVID-19 Patients—A Scoping Review
Authors: Mędrzycka-Dąbrowska Wioletta , Lange Sandra , Zorena Katarzyna , Dąbrowski Sebastian , Ozga Dorota , Tomaszek Lucyna
Published: May 2021

Introduction: The spread of multidrug-resistant pathogens is a serious problem and challenge for the whole medical community. Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections in immunocompromised patients have a severe course and may be fatal. Increasingly, these bacteria are exhibiting resistance to carbapenem antibiotics, which have been used as so-called drugs of last resort. The emergence of the new coronavirus and the pandemic that it has caused require changes to protect against the spread of the new SARS-CoV-2. These changes paradoxically may contribute to the spread of other infections. Methods: PubMed, Cochrane Library databases were searched using relevant keywords. A literature review of carbapenem-resistant Klebsiella pneumoniae infection in patients hospitalized for COVID-19 was conducted according to PRISMA recommendations. A written review protocol was not prepared. Results: 1016 studies in scientific databases were searched. After rejecting duplicate studies, 964 results were obtained. Inclusion and exclusion criteria were then applied, and studies were qualitatively analyzed. Finally, 11 studies were included in the review. The results of infected patients were from six countries. The prevalence of CRKP in Covid-19 patients ranged from 0.35–53%. The majority of CRKP infected patients were male (85%), with a mean age of 61 years. Among isolates, the predominant genes were KPC, OXY-48, CTX-M, TEM, NDM and SHV. Conclusion: The results presented in our review indicate the necessity of paying attention to carbapenem-resistant Klebsiella pneumoniae infections in patients with COVID-19. In order to prevent the increase of bacterial resistance, rational antibiotic therapy should be used, as well as continuous control and surveillance of hospital infections caused by multidrug-resistant organisms.
Combined Administration of Fibrinogen and Factor XIII Concentrate Does Not Improve Dilutional Coagulopathy Superiorly Than Sole Fibrinogen Therapy: Results of an In-Vitro Thrombelastographic Study
Authors: Schneck Emmanuel , Muelich Marcus , Markmann Melanie , Edinger Fabian , Cooper Nina , Moeller Annette , Bein Gregor , Hecker Andreas , Koch Christian , Sander Michael , Wolff Matthias
Published: May 2021

The early administration of fibrinogen has gained wide acceptance for the treatment of major hemorrhage, whereas the substitution of coagulation factor XIII (FXIII) is only supported by a low level of evidence. This study aimed to answer the question of whether a combined therapy of fibrinogen/FXIII substitution performs superiorly to sole fibrinogen administration in the treatment of dilutional coagulopathy. An in-vitro model of massive transfusion was used to compare the effect of combined fibrinogen/FXIII administration to that of sole fibrinogen therapy for the treatment of dilutional coagulopathy. For this purpose, the blood of red blood cell concentrates, fresh frozen plasma, and platelet concentrates were reconstituted in a ratio of 4:4:1, and then diluted with gelatin by 20% and 40%, respectively. Clot formation and stability were analyzed by thrombelastography. Both sole fibrinogen therapy (equivalent to 50 mg/kg) and the combined administration of fibrinogen (equivalent to 50 mg/kg) and FXIII (equivalent to 75 International Units (IU)/kg) increased fibrinogen-dependent mean clot firmness independently of the degree of dilution (20% dilution: 7 (6.3–7.8) mm; 20% dilution fibrinogen: 13.5 (13–17.3) mm; 20% dilution fibrinogen/FXIII: 16.5 (15.3–18.8) mm; 40% dilution: 3 (2–3.8) mm; 40% dilution fibrinogen: 8 (7–11.3) mm; 40% dilution fibrinogen/FXIII: 10 (8.3–11.8) mm; all p < 0.01). However, no differences were identified between the two treatment arms. Compared to fibrinogen therapy, no beneficial effect of the combined administration of fibrinogen and FXIII for the treatment of dilutional coagulopathy was detected in this in-vitro massive transfusion model. The result was independent of the degree of dilution.
Laparoendoscopic Single Site Hysterectomy: Literature Review and Procedure Description
Authors: Mereu Liliana , Dalprà Francesca , Tateo Saverio
Published: May 2021

Laparoendoscopic single site surgery (LESS) refers to a spectrum of surgical techniques that allow the performance of laparoscopic surgery through consolidation of all ports into one surgical incision. LESS has emerged as a potentially less invasive alternative to multiport laparoscopy and in the last year in gynecology; hence, this approach has been largely applied for selective indications to perform total hysterectomy. We performed a literature review on single site hysterectomy and described indications and technique, highlighting practical problems, pointers, limitations and recent technical development as robotic assistance.
Serum C-Reactive Protein and Interleukin-6 Levels as Biomarkers for Disease Severity and Clinical Outcomes in Patients with Idiopathic Granulomatous Mastitis
Authors: Huang Yi-Min , Lo Chiao , Cheng Chiao-Feng , Lu Cheng-Hsun , Hsieh Song-Chou , Li Ko-Jen
Published: May 2021

Idiopathic granulomatous mastitis (IGM) is a rare inflammatory breast disease mimicking breast cancer. Limited research has been conducted on the application of serum biomarkers. This study aims to investigate the association of serum biomarkers with disease severity in patients with IGM. From November 2011 to March 2020, medical records of patients with IGM were reviewed. Serum cytokine levels were measured in patients and healthy controls between July 2018 and March 2020. A total of 41 patients with histologically proven IGM were found. Serum interleukin (IL)-6 level was significantly higher in patients with IGM (n = 11) than healthy controls (n = 7). Serum IL-6 and C-reactive protein (CRP) levels were significantly higher in patients with severe disease than mild and moderate disease. Serum IL-6 (Spearman’s ρ = 0.855; p < 0.001) and CRP (Spearman’s ρ = 0.838; p = 0.001) levels were associated with time to resolution. A higher serum CRP level was associated with a longer time to resolution (B = 0.322; p < 0.001) in multiple linear regression analysis. Serum IL-6 and CRP levels can be used as biomarkers for the evaluation of disease severity in IGM. IL-6 may play a crucial role in the immunopathology of IGM.
Bodyweight Measures and Lifestyle Habits in Individuals with Multiple Sclerosis and Moderate to Severe Disability
Authors: Livne-Margolin Moran , Tokatly Latzer Itay , Pinhas-Hamiel Orit , Harari Gil , Achiron Anat
Published: May 2021

Multiple sclerosis (MS) is a chronic disease marked by progressive disability and decreased mobility over time. We studied whether individuals with MS of higher disability levels will be more overweight/obese as a result of their immobility and/or recurrent steroid treatments. In a prospective study, 130 individuals with MS and significant disability were classified according to the Expanded Disability Status Scale (EDSS) score as belonging to four groups: EDSS 3.0–4.0 (n = 31, 24%), EDSS 4.5–5.5 (n = 24, 18%), EDSS = 6.0 (n = 44, 34%) and EDSS ≥ 6.5 (n = 31, 24%). Medical history, body mass index (BMI), waist circumference and the level of engagement in physical activity were obtained. The mean ± standard error age was 55.8 ± 0.5 years, disease duration 18.2 ± 1.0 years and EDSS score 5.5 ± 0.1. Disease duration, the number of steroid courses per disease duration, weight, BMI and physical activity did not differ according to the four disability groups. The mean waist circumference increased significantly with increased severity of EDSS, p = 0.03. Increased disability in individuals with MS was not correlated with disease duration, lifestyle habits or overweight/obesity. However, increased disability was associated with central obesity.
Comprehensive Wind and Wave Statistics and Extreme Values for Design and Analysis of Marine Structures in the Adriatic Sea
Authors: Katalinić Marko , Parunov Joško
Published: May 2021

Wind and waves present the main causes of environmental loading on seagoing ships and offshore structures. Thus, its detailed understanding can improve the design and maintenance of these structures. Wind and wave statistical models are developed based on the WorldWaves database for the Adriatic Sea: for the entire Adriatic Sea as a whole, divided into three regions and for 39 uniformly spaced locations across the offshore Adriatic. Model parameters are fitted and presented for each case, following the conditional modelling approach, i.e., the marginal distribution of significant wave height and conditional distribution of peak period and wind speed. Extreme significant wave heights were evaluated for 20-, 50- and 100-year return periods. The presented data provide a consistent and comprehensive description of metocean (wind and wave) climate in the Adriatic Sea that can serve as input for almost all kind of analyses of ships and offshore structures.