bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatio-Temporal Variation of Health Production Efficiency Considering Environmental Pollution in China Based on Modified EBM and Spatial Econometric Model
Authors: Liu Fan , Li Gen , Zhou Ying , Ma Yinghui , Wang Tao
Published: December 2021

In order to strengthen the construction of China's health industry and improve the health of the people, based on the data of 31 provinces and cities in China from 2009 to 2019, the improved EBM model is used to measure the health production efficiency of each region, and Moran index is used to study the Spatio-temporal variation of health production efficiency of each province. Finally, the spatial econometric model is applied to study the influencing factors of the Spatio-temporal variation of health production efficiency. The results show that generally speaking, the average efficiency of 31 provinces and cities is above 0.7, and the average efficiency of some regions is above 1. From the perspective of time variation, the average efficiency value in the eastern region and the middle region increases from 0.816 to 0.882 and from 0.851 to 0.861, respectively. However, the average efficiency value in the western region and northeast region decreases from 0.861 to 0.83 and from 0.864 to 0.805, respectively. From the perspective of spatial distribution, HH agglomeration and LL agglomeration exist in most regions. By comparing Moran scatter plots in 2009 and 2019, it is found that the quadrants of most regions remain unchanged, and LL agglomeration is the main agglomeration type in local space. There is a significant spatial dependence among different regions. From the perspective of spatial empirical results, Pgdp, Med, and Pd have a positive effect on health production efficiency. The direct effect and indirect effect of Pgdp, Med, and Gov all pass the significance test of 1%, indicating that there are spatial spillover effects of the three indicators. Each region should reasonably deal with the spillover effect of surrounding regions, vigorously develop economic activities, carry out cooperation with surrounding regions and apply demonstration effect to accelerate the development of overall health production.
Application of WOA–SVR in Seed Vigor of High-Voltage Electric Field Treatment on Aged Cotton (Gossypium spp.) Seeds
Authors: Song Zhanhua , Ma Junxiang , Peng Qian , Liu Baoji , Li Fade , Sun Xiangyun , Liu Mochen , Yan Yinfa
Published: December 2021

When seeds are treated with a high-voltage electric field (HVEF) to improve seed vigor, due to the large differences in the biological electromagnetic effects on different types of seeds, the methods of variance analysis and regression analysis based on data statistics are generally used to construct the optimal electric field dose prediction model; however, the generalization performance of the prediction model tends to be poor. To solve this problem, the electric intensity, frequency and treatment time were taken as the input variables for hybrid support vector regression (SVR) analysis to establish the prediction model of the seed comprehensive germination index. The whale optimization algorithm (WOA) was used to optimize the kernel parameters of the SVR. The optimized hybrid WOA–SVR model predicted the optimal comprehensive germination index of aged cotton (Gossypium spp.) seeds to be 329, the optimal HVEF dosage was 3.64 kV/cm × 99 s, and the frequency was 1.4 Hz. The aged cotton seeds were treated with the optimal HVEF and the germination test was carried out. Compared with the check (CK), the comprehensive germination index of seeds increased by 48%. The research results provided a new method and new idea for the optimal design of parameters for seed treatment with HVEF.
Monitoring Olive Oil Mill Wastewater Disposal Sites Using Sentinel-2 and PlanetScope Satellite Images: Case Studies in Tunisia and Greece
Authors: Issaoui Wissal , Alexakis Dimitrios D. , Nasr Imen Hamdi , Argyriou Athanasios V. , Alevizos Evangelos , Papadopoulos Nikos , Inoubli Mohamed Hédi
Published: December 2021

Mediterranean countries are known worldwide for their significant contribution to olive oil production, which generates large amounts of olive mill wastewater (OMW) that degrades land and water environments near the disposal sites. OMW consists of organic substances with high concentrations of phenolic compounds along with inorganic particles. The aim of this study is to assess the effectiveness of satellite image analysis techniques using multispectral satellite data with high (PlanetScope, 3 × 3 m) and medium (Sentinel-2, 10 × 10 m) spatial resolution to detect Olive Mill Wastewater (OMW) disposal sites, both in the SidiBouzid region (Tunisia) and in the broader Rethymno region on the island of Crete, (Greece). Documentation of the sites was carried out by collecting spectral signatures of OMW at temporal periods. The study integrates the application of a variety of spectral vegetation indices (VIs), such as the Normalized Difference Vegetation Index (NDVI), in order to evaluate their efficiency in detecting OMW disposal areas. Furthermore, a set of image-processing methods was applied on satellite images to improve the monitoring of OMW ponds including the false-color composites (FCC), the Principal Component Analysis (PCA), and image fusion. Finally, different classification algorithms, such as the ISODATA, the maximum likelihood (ML), and the Support Vector Machine (SVM) were applied to both satellite images in order to assist in the overall approach to effectively detect the sites. The results obtained from different approaches were compared, evaluating the efficiency of Sentinel-2 and PlanetScope images to detect and monitor OMW disposal areas under different morphological environments.
Quantitative Research on Profitability Measures in the Polish Meat and Poultry Industries
Authors: Zielińska-Chmielewska Anna , Kaźmierczyk Jerzy , Jaźwiński Ireneusz
Published: December 2021

Business entities strive for continuous adaptation to changing situations and needs. The decisions of business entities entangled in multifaceted processes of economic, social, and environmental progress must be taken on the basis of reliable knowledge, developed know-how, scrupulous recognition of the initial state, and foresight of the multiple consequences of business actions over a long horizon. In such a situation, the measurement of financial efficiency in terms of the profitability of enterprises in meat and poultry industries is extremely desired and provides valuable information on the necessary modifications to reduce the potential risks of business operation. The Polish meat and poultry industries should take into account current and future market requirements, competition, and consumer response. The dynamic progress of technology is forced to take appropriate steps to improve and modernize products, services, and methods of solving profit losses. The aim of the paper is to calculate and evaluate the statistical relationships between profitability ratios in Polish meat and poultry enterprises divided into four groups: slaughterhouses, meat enterprises (small, medium, and large), poultry meat enterprises, and meat trade enterprises. In the theoretical part of the study, methods of descriptive, comparative, deductive, and synthetic analyses were used. In the practical part of the study, panel data from the entire meat and poultry industries in the period from 2010 to 2019 were used. For the measurement of financial efficiency, methods, such as financial indicator analysis, panel database modeling, and nonparametric ANOVA, were applied. The ANOVA method was used to test only the statistically significant relationships between profitability ratios across all groups of examined enterprises in the meat and poultry industries. To summarize, the optimal level of profitability was achieved by all groups of examined enterprises, except small meat enterprises. The highest financial efficiency in the area of profitability was reached by poultry enterprises. Moreover, financial support for small companies in the meat industry can bring tangible benefits such as maintaining a diversified product range locally and transforming small meat companies into buying centers for the local community. Both are effective solutions, especially in view of the post-pandemic situation.
Antimicrobial Activity of Polyphenols and Natural Polyphenolic Extracts on Clinical Isolates
Authors: Manso Tamara , Lores Marta , de Miguel Trinidad
Published: December 2021

Antibiotic resistance is a growing global problem that affects people, animals, the environment, and the economy. Many clinically relevant bacteria have become resistant to antibiotics, and this fact is emerging as one of the major threats to public health. The lack of new antibiotics, which is due to their time-consuming and costly development, exacerbates the problem. Therefore, it is necessary to identify new antimicrobial agents to treat bacterial and fungal infections. Plant extracts, which are valuable sources of bioactive compounds, mainly polyphenols, play an important role as a new strategy to combat pathogenic microorganisms. There is an extensive body of supporting evidence for the potent antibacterial and antifungal activities of polyphenols. Furthermore, some polyphenols show a synergistic effect when combined with antibiotics and antifungals, suggesting a promising alternative for therapeutic strategies against antibiotic resistance. However, only a few articles are found when searching the antibacterial or antifungal activities of polyphenols employing clinical isolates. Hence, this review focuses on the antimicrobial activity of polyphenols and extracts rich in polyphenols on clinical isolates, organized according to the World Health Organization priority pathogens classification.
Genoprotective Effect of Some Flavonoids against Genotoxic Damage Induced by X-rays In Vivo: Relationship between Structure and Activity
Authors: Alcaraz Miguel , Olivares Amparo , Achel Daniel Gyingiri , García-Gamuz José Antonio , Castillo Julián , Alcaraz-Saura Miguel
Published: December 2021

Flavonoids constitute a group of polyphenolic compounds characterized by a common gamma-benzo- pyrone structure considered in numerous biological systems to possess antioxidant capacity. Among the different applications of flavonoids, its genoprotective capacity against damage induced by ionizing radiation stands out, which has been related to antioxidant activity and its chemical structure. In this study, we determined the frequency of appearance of micronucleus in vivo by means of the micronucleus assay. This was conducted in mice treated with different flavonoids before and after exposure to 470 mGy X-rays; thereafter, their bone marrow polychromatophilic erythrocytes were evaluated to establish the structural factors enhancing the observed genoprotective effect. Our results in vivo show that the presence of a monomeric flavan-3-ol type structure, with absence of carbonyl group in position C4 of ring C, absence of conjugation between the carbons bearing the C2 = C3 double bond and the said ring, presence of a catechol group in ring B and characteristic hydroxylation in positions 5 and 7 of ring A are the structural characteristics that determine the highest degree of genoprotection. Additionally, a certain degree of polymerization of this flavonoid monomer, but maintaining significant levels of monomers and dimers, contributes to increasing the degree of genoprotection in the animals studied at both times of their administration (before and after exposure to X-rays).
A Proposal for Multimodal Emotion Recognition Using Aural Transformers and Action Units on RAVDESS Dataset
Authors: Luna-Jiménez Cristina , Kleinlein Ricardo , Griol David , Callejas Zoraida , Montero Juan M. , Fernández-Martínez Fernando
Published: December 2021

Emotion recognition is attracting the attention of the research community due to its multiple applications in different fields, such as medicine or autonomous driving. In this paper, we proposed an automatic emotion recognizer system that consisted of a speech emotion recognizer (SER) and a facial emotion recognizer (FER). For the SER, we evaluated a pre-trained xlsr-Wav2Vec2.0 transformer using two transfer-learning techniques: embedding extraction and fine-tuning. The best accuracy results were achieved when we fine-tuned the whole model by appending a multilayer perceptron on top of it, confirming that the training was more robust when it did not start from scratch and the previous knowledge of the network was similar to the task to adapt. Regarding the facial emotion recognizer, we extracted the Action Units of the videos and compared the performance between employing static models against sequential models. Results showed that sequential models beat static models by a narrow difference. Error analysis reported that the visual systems could improve with a detector of high-emotional load frames, which opened a new line of research to discover new ways to learn from videos. Finally, combining these two modalities with a late fusion strategy, we achieved 86.70% accuracy on the RAVDESS dataset on a subject-wise 5-CV evaluation, classifying eight emotions. Results demonstrated that these modalities carried relevant information to detect users’ emotional state and their combination allowed to improve the final system performance.
Iterative Named Entity Recognition with Conditional Random Fields
Authors: Alves-Pinto Ana , Demus Christoph , Spranger Michael , Labudde Dirk , Hobley Eleanor
Published: December 2021

Named entity recognition (NER) constitutes an important step in the processing of unstructured text content for the extraction of information as well as for the computer-supported analysis of large amounts of digital data via machine learning methods. However, NER often relies on domain-specific knowledge, being conducted manually in a time- and human-resource-intensive process. These can be reduced with statistical models performing NER automatically. The current work investigates whether Conditional Random Fields (CRF) can be efficiently trained for NER in German texts, by means of an iterative procedure combining self-learning with a manual annotation–active learning–component. The training dataset increases continuously with the iterative procedure. Whilst self-learning did not markedly improve the performance of the CRF for NER, the manual annotation of sentences with the lowest probability of correct prediction clearly improved the model F1-score and simultaneously reduced the amount of manual annotation required to train the model. A model with an F1-score of 0.885 was able to be trained in 11.4 h.
Root Resorption of Adjacent Teeth Associated with Maxillary Canine Impaction in the Saudi Arabian Population: A Cross-Sectional Cone-Beam Computed Tomography Study
Authors: Alassiry Ahmed Mohammed , Hakami Zaki
Published: December 2021

This study aimed to identify the location of root resorption in relation to an impacted maxillary canine and grade its severity using cone-beam computed tomography (CBCT) in the Saudi Arabian population. Materials and Methods: CBCT scans of 169 patients with maxillary canine impaction were evaluated. The location and the severity of root resorption of the affected tooth in relation to the impacted maxillary canine were recorded for each patient. Results: a total 204 impacted maxillary canines caused root resorption in 218 adjacent teeth. Maximum root resorption was present in 63.3% of the apical one-third of the root and 37.6% of the palatal surfaces. There was mild root resorption in 55%, moderate in 10% and severe in 35%. There was no statistically significant difference between the gender, age, type of impaction, side of impaction, and the number, location, or degree of root resorption. Multiple logistic regression models showed significant association (p = 0.024) between gender, type of impaction, and root resorption. A significant correlation was found between the level and the surface of the root resorption (p = 0.018). Conclusion: In the Saudi population, apical one-third root levels and palatal surfaces were primarily involved in root resorption caused by impacted canines. The females with bilateral canine impaction were more likely affected by root resorption.
Automated Classification of Unstructured Bilingual Software Bug Reports: An Industrial Case Study Research
Authors: Köksal Ömer , Tekinerdogan Bedir
Published: December 2021

Software bug report classification is a critical process to understand the nature, implications, and causes of software failures. Furthermore, classification enables a fast and appropriate reaction to software bugs. However, for large-scale projects, one must deal with a broad set of bugs from multiple types. In this context, manually classifying bugs becomes cumbersome and time-consuming. Although several studies have addressed automated bug classification using machine learning techniques, they have mainly focused on academic case studies, open-source software, and unilingual text input. This paper presents our automated bug classification approach applied and validated in an industrial case study. In contrast to earlier studies, our study is applied to a commercial software system based on unstructured bilingual bug reports written in English and Turkish. The presented approach adopts and integrates machine learning (ML), text mining, and natural language processing (NLP) techniques to support the classification of software bugs. The approach has been applied within an industrial case study. Compared to manual classification, our results show that bug classification can be automated and even performs better than manual bug classification. Our study shows that the presented approach and the corresponding tools effectively reduce the manual classification time and effort.
Interwoven versus Knitted Self-Expandable Metallic Stents: A Comparison Study of Stent-Induced Tissue Hyperplasia in the Rat Esophagus
Authors: Kang Jeon Min , Oh Dongwook , Kim Song Hee , Ryu Dae Sung , Park Yubeen , Won Dong-Sung , Kim Ji Won , Zeng Chu Hui , Park Jung-Hoon , Lee Sang Soo
Published: December 2021

This study investigated whether interwoven self-expandable metallic stent (I-SEMS) placement suppresses stent-induced tissue hyperplasia compared with conventional knitted self-expandable metallic stent (K-SEMS) placement in a rat esophageal model. Twelve rats were randomly assigned to the I-SEMS (n = 6) and K-SEMS (n = 6) groups. All rats were sacrificed 4 weeks after the stent placement. The degree of stent-induced tissue hyperplasia on esophagography and histologic examination was compared between the groups. Stent placement was technically successful in all rats. Esophagography revealed significantly greater mean luminal diameter of the stented esophagus in the I-SEMS group than in the K-SEMS group (p < 0.001). Histologic examination revealed a significantly lower percentage of tissue hyperplasia area and a significantly thinner submucosal fibrosis in the I-SEMS group than in the K-SEMS group (all p < 0.001). There were no significant differences in the thickness of the epithelial layers (p = 0.290) and degree of inflammatory cell infiltration (p = 0.506). Formation of stent-induced tissue hyperplasia was evident with both I-SEMS and K-SEMS. Placement of I-SEMSs with a small cell size and high flexibility seems to be effective in suppressing stent-induced tissue hyperplasia compared with placement of K-SEMSs in rat esophageal models.
A Study on PF–IFF-Based Diagnosis Model of Plant Equipment Failure
Authors: Seo Min-Young , Hwang Se-Yun , Lee Jang-Hyun , Kim Jae-Gon , Jun Hong-Bae
Published: December 2021

There are two types of maintenance policies for equipment: breakdown maintenance and preventive maintenance. In the case of applying preventive maintenance, the maintenance is carried out based on time or the condition of the equipment. However, with the development of Information and Communications Technologies (ICT) and the Internet of Things (IoT) technology, the data collected from equipment has rapidly increased and the use of Condition-Based Maintenance (CBM) to perform appropriate maintenance based on the condition of the equipment is increasing. In this study, based on gathered sensor data, we introduce an approach to diagnosing the condition of the equipment by extracting specific data features related to the types of failures that occur with equipment. To this end, we used the K-means clustering method, support vector machine (SVM) classifier, and Pattern Frequency–Inverse Failure mode Frequency (PF–IFF) method with the Term Frequency–Inverse Document Frequency (TF–IDF) method. As a case study, we applied the proposed approach to a centrifugal pump and carried out computational experiments for assessing the performance and validity of the proposed approach.
Effect of Environment-Related Cues on Auditory Distance Perception in the Context of Audio-Only Augmented Reality
Authors: Martin Vincent , Viaud-Delmon Isabelle , Warusfel Olivier
Published: December 2021

Audio-only augmented reality consists of enhancing a real environment with virtual sound events. A seamless integration of the virtual events within the environment requires processing them with artificial spatialization and reverberation effects that simulate the acoustic properties of the room. However, in augmented reality, the visual and acoustic environment of the listener may not be fully mastered. This study aims to gain some insight into the acoustic cues (intensity and reverberation) that are used by the listener to form an auditory distance judgment, and to observe if these strategies can be influenced by the listener’s environment. To do so, we present a perceptual evaluation of two distance-rendering models informed by a measured Spatial Room Impulse Response. The choice of the rendering methods was made to design stimuli categories in which the availability and reproduction quality of acoustic cues are different. The proposed models have been evaluated in an online experiment gathering 108 participants who were asked to provide judgments of auditory distance about a stationary source. To evaluate the importance of environmental cues, participants had to describe the environment in which they were running the experiment, and more specifically the volume of the room and the distance to the wall they were facing. It could be shown that these context cues had a limited, but significant, influence on the perceived auditory distance.
Dimensional Optimization of TiO2 Nanodisk Photonic Crystals on Lead Iodide (MAPbI3) Perovskite Solar Cells by Using FDTD Simulations
Authors: Hasanah Lilik , Ashidiq Adryan , Pawinanto Roer Eka , Mulyanti Budi , Wulandari Chandra , Wiendartun  , Md. Zain Ahmad Rifqi
Published: December 2021

Perovskite solar cells (PSC) are currently exhibiting reproducible high efficiency, low-cost manufacturing, and scalable electron transport layers (ETL), which are becoming increasingly important. The application of photonic crystals (PC) on solar cells has been proven to enhance light harvesting and lead solar cells to adjust the propagation and distribution of photons. In this paper, the optimization of a two-dimensional nanodisk PC introduced in ETL with an organic-inorganic lead-iodide perovskite (methylammonium lead-iodide, MAPbI3) as the absorber layer was studied. A finite-difference time-domain (FDTD) simulation was used to evaluate the optical performance of PSC with various lattice constants and a radius of nanodisk photonic crystals. According to the simulation, the optimum lattice constant and PC radius applied to ETL are 500 nm and 225 nm, respectively. This optimum design enhances PSC absorption performance by more than 94% of incident light.
Spatial and Temporal Variations of Extreme Precipitation in Central Asia during 1982–2020
Authors: Tian Yalin , Yan Zhongwei , Li Zhen
Published: December 2021

As one of the largest arid and semi-arid regions in the world, central Asia (CA) is very sensitive to changes in regional climate. However, because of the poor continuity of daily observational precipitation records in CA, the spatial and temporal variations of extreme precipitation in recent decades remain unclear. Considering their good spatial and temporal continuity, gridded data, such as Climate Prediction Center (CPC) global precipitation, and reanalysis data, such as ERA-Interim (ERA), are helpful for exploring the spatial–temporal variations of extreme precipitation. This study evaluates how well CPC and ERA can represent observed precipitation extremes by comparing the differences in eight extreme precipitation indices and observation data at 84 meteorological stations. The results indicate that the CPC (except for 1979–1981) is more suitable for depicting changes in precipitation extremes. Based on the CPC data for the period 1982–2020, we found that seven indices of precipitation extremes, including consecutive wet days (CWD), max1-day precipitation amount (Rx1day), max5-day precipitation amount (Rx5day), number of heavy precipitation days (R10), very wet days (R95p), annual total precipitation in wet days (PRCPTOT), and simple precipitation intensity index (SDII) have increased by 0.2 d/10a, 0.9 mm/10a, 1.8 mm/10a, 0.3 d/10, 8.4 mm/10a, 14.3 mm/10a and 0.1 mm/d/10a, respectively, and the consecutive dry days (CDDs) have decreased by −3.10 d/10a. It is notable that CDDs decreased significantly in the north of Xinjiang (XJ) but increased in Kyrgyzstan (KG), Tajikistan (TI), and eastern Turkmenistan (TX). The other indices increased clearly in the west of XJ, north of Kazakhstan (KZ), and east of KG but decreased in the south of KG, TI, and parts of XJ. For most indices, the largest change occurred in spring, the main season of precipitation in CA. Therefore, the large-scale atmospheric circulation in April is analyzed to contrast between the most and least precipitation years for the region. A typical circulation pattern in April for those extremely wet years includes an abnormal low-pressure center at 850 hpa to the east of the Caspian Sea, which enhances the southerly winds from the Indian Ocean and hence the transportation of water vapor required for precipitation into CA. This abnormal circulation pattern occurred more frequently after 2001 than before, thus partly explaining the recent increasing trends of precipitation extremes in CA.
Theoretical Study and Numerical Experiment on the Influence of Trend Changes on Correlation Coefficient
Authors: Da Chaojiu , Hu Lei , Shen Binglu , Yang Yuyin , Wan Shiquan , Song Jian
Published: December 2021

When one of two time series undergoes an obvious change in trend, the correlation coefficient between the two will be distorted. In the context of global warming, most meteorological time series have obvious linear trends, so how do variations in these trends affect the correlation coefficient? In this paper, the correlation between time series with trend changes is studied theoretically and numerically. Adopting the trend coefficient, which reflects the nature and size of the trend change, we derive a formula r = f(k, l) for the correlation coefficient of time series X and Y with respective trend coefficients k and l. Analysis of the function graph shows that the changes in correlation coefficient with respect to the trend coefficients produce a twisted saddle surface, and the saddle point coordinates are given by the trend coefficients of time series X and Y with the opposite signs. The curve f(k, l) = f(0, 0) divides the coordinate planes into regions where f(k, l) > f(0, 0) and f(k, l) < f(0, 0). When the trend coefficients k and l are very small and the correlation coefficient is also very small, then k > 0 and l > 0 (or k < 0 and l < 0) amplifies a positive correlation, whereas k > 0 and l < 0 (or k < 0 and l > 0) amplifies a negative correlation, as found in previous research. Finally, experiments using meteorological data verify the reliability and effectiveness of the theory.
Progress on the Application of Bortezomib and Bortezomib-Based Nanoformulations
Authors: Liu Jianhao , Zhao Ruogang , Jiang Xiaowen , Li Zhaohuan , Zhang Bo
Published: December 2021

Bortezomib (BTZ) is the first proteasome inhibitor approved by the Food and Drug Administration. It can bind to the amino acid residues of the 26S proteasome, thereby causing the death of tumor cells. BTZ plays an irreplaceable role in the treatment of mantle cell lymphoma and multiple myeloma. Moreover, its use in the treatment of other hematological cancers and solid tumors has been investigated in numerous clinical trials and preclinical studies. Nevertheless, the applications of BTZ are limited due to its insufficient specificity, poor permeability, and low bioavailability. Therefore, in recent years, different BTZ-based drug delivery systems have been evaluated. In this review, we firstly discussed the functions of proteasome inhibitors and their mechanisms of action. Secondly, the properties of BTZ, as well as recent advances in both clinical and preclinical research, were reviewed. Finally, progress in research regarding BTZ-based nanoformulations was summarized.
Rapamycin Suppresses Penile NADPH Oxidase Activity to Preserve Erectile Function in Mice Fed a Western Diet
Authors: La Favor Justin D. , Pierre Clifford J. , Bivalacqua Trinity J. , Burnett Arthur L.
Published: December 2021

The mechanistic target of rapamycin (mTOR) is a nutrient-sensitive cellular signaling kinase that has been implicated in the excess production of reactive oxygen species (ROS). NADPH oxidase-derived ROS have been implicated in erectile dysfunction pathogenesis. The objective of this study was to determine if mTOR is an activator of NADPH oxidase in the penis and to determine the functional relevance of this pathway in a translationally relevant model of diet-induced erectile dysfunction. Male mice were fed a control diet or a high-fat, high-sucrose Western style diet (WD) for 12 weeks and treated with vehicle or rapamycin for the final 4 weeks of the dietary intervention. Following the intervention, erectile function was assessed by cavernous nerve-stimulated intracavernous pressure measurement, in vivo ROS production was measured in the penis using a microdialysis approach, and relative protein contents from the corpus cavernosum were determined by Western blot. Erectile function was impaired in vehicle treated WD-mice and was preserved in rapamycin treated WD-mice. Penile NADPH oxidase-mediated ROS were elevated in WD-mice and suppressed by rapamycin treatment. Western blot analysis suggests mTOR activation with WD by increased active site phosphorylation of mTOR and p70S6K, and increased expression of NADPH oxidase subunits, all of which were suppressed by rapamycin. These data suggest that mTOR is an upstream mediator of NADPH oxidase in the corpus cavernosum in response to a chronic Western diet, which has an adverse effect on erectile function.
MicroRNA-Enriched Exosomes from Different Sources of Mesenchymal Stem Cells Can Differentially Modulate Functions of Immune Cells and Neurogenesis
Authors: Soni Naina , Gupta Suchi , Rawat Surender , Krishnakumar Vishnu , Mohanty Sujata , Banerjee Arup
Published: December 2021

Adult Mesenchymal stem cells-derived exosomes carry several biologically active molecules that play prominent roles in controlling disease manifestations. The content of these exosomes, their functions, and effect on the immune cells may differ depending on their tissue sources. Therefore, in this study, we purified the exosomes from three different sources and, using the RNA-Seq approach, highly abundant microRNAs were identified and compared between exosomes and parental cells. The effects of exosomes on different immune cells were studied in vitro by incubating exosomes with PBMC and neutrophils and assessing their functions. The expression levels of several miRNAs varied within the different MSCs and exosomes. Additionally, the expression profile of most of the miRNAs was not similar to that of their respective sources. Exosomes isolated from different sources had different abilities to induce the process of neurogenesis and angiogenesis. Moreover, these exosomes demonstrated their varying effect on PBMC proliferation, neutrophil survival, and NET formation, highlighting their versatility and broad interaction with immune cells. The knowledge gained from this study will improve our understanding of the miRNA landscape of exosomes from hMSCs and provide a resource for further improving our understanding of exosome cargo and their interaction with immune cells.
Graphene-Based Materials Prove to Be a Promising Candidate for Nerve Regeneration Following Peripheral Nerve Injury
Authors: Aleemardani Mina , Zare Pariya , Seifalian Amelia , Bagher Zohreh , Seifalian Alexander M.
Published: December 2021

Peripheral nerve injury is a common medical condition that has a great impact on patient quality of life. Currently, surgical management is considered to be a gold standard first-line treatment; however, is often not successful and requires further surgical procedures. Commercially available FDA- and CE-approved decellularized nerve conduits offer considerable benefits to patients suffering from a completely transected nerve but they fail to support neural regeneration in gaps > 30 mm. To address this unmet clinical need, current research is focused on biomaterial-based therapies to regenerate dysfunctional neural tissues, specifically damaged peripheral nerve, and spinal cord. Recently, attention has been paid to the capability of graphene-based materials (GBMs) to develop bifunctional scaffolds for promoting nerve regeneration, often via supporting enhanced neural differentiation. The unique features of GBMs have been applied to fabricate an electroactive conductive surface in order to direct stem cells and improve neural proliferation and differentiation. The use of GBMs for nerve tissue engineering (NTE) is considered an emerging technology bringing hope to peripheral nerve injury repair, with some products already in preclinical stages. This review assesses the last six years of research in the field of GBMs application in NTE, focusing on the fabrication and effects of GBMs for neurogenesis in various scaffold forms, including electrospun fibres, films, hydrogels, foams, 3D printing, and bioprinting.
Median Nerve Stimulation Facilitates the Identification of Somatotopy of the Subthalamic Nucleus in Parkinson’s Disease Patients under Inhalational Anesthesia
Authors: Chen Yu-Chen , Kuo Chang-Chih , Chen Shin-Yuan , Chen Tsung-Ying , Pan Yan-Hong , Wang Po-Kai , Tsai Sheng-Tzung
Published: December 2021

Deep brain stimulation (DBS) improves Parkinson’s disease (PD) symptoms by suppressing neuropathological oscillations. These oscillations are also modulated by inhalational anesthetics used during DBS surgery in some patients, influencing electrode placement accuracy. We sought to evaluate a method that could avoid these effects. We recorded subthalamic nucleus (STN) neuronal firings in 11 PD patients undergoing DBS under inhalational anesthesia. Microelectrode recording (MER) during DBS was collected under median nerve stimulation (MNS) delivered at 5, 20, and 90 Hz frequencies and without MNS. We analyzed the spike firing rate and neuronal activity with power spectral density (PSD), and assessed correlations between the neuronal oscillation parameters and clinical motor outcomes. No patient experienced adverse effects during or after DBS surgery. PSD analysis revealed that peripheral 20 Hz MNS produced significant differences in the dorsal and ventral subthalamic nucleus (STN) between the beta band oscillation (16.9 ± 7.0% versus 13.5 ± 4.8%, respectively) and gamma band oscillation (56.0 ± 13.7% versus 66.3 ± 9.4%, respectively) (p < 0.05). Moreover, 20-Hz MNS entrained neural oscillation over the dorsal STN, which correlated positively with motor disabilities. MNS allowed localization of the sensorimotor STN and identified neural characteristics under inhalational anesthesia. This paradigm may help identify an alternative method to facilitate STN identification and DBS surgery under inhalational anesthesia.
Design Optimisation of Fixed and Adaptive Shading Devices on Four Façade Orientations of a High-Rise Office Building in the Tropics
Authors: Mangkuto Rizki A. , Koerniawan Mochamad Donny , Apriliyanthi Sri Rahma , Lubis Irma Handayani , Atthaillah  , Hensen Jan L. M. , Paramita Beta
Published: December 2021

Optimisation of shading devices in buildings is a broadly investigated topic; however, most studies only focus on a single façade orientation, since the observed buildings are typically located in high latitude regions. However, in tropical regions, optimisation of all façade orientations is required due to the relatively high solar radiation and long sunshine duration. While adaptive shading devices are a promising solution, they are not without disadvantages, and as such a combination of adaptive shading devices and a fixed shading device shall be considered. This research therefore aims to design the optimum internal shading devices on four façade orientations of a high-rise office building in a tropical city, considering fixed and adaptive shading design options, and to determine the impact on annual daylight performance using computational modelling and simulation. The simulation is carried out under: (1) fixed design option, focusing on the numbers and width of slats; and (2) adaptive design option, focusing on the slat angle on various conditions. It is found that both sDA300/50% and ASE1000,250 are only influenced by the orientation. Under the fixed design option, the sDA300/50% and ASE1000,250 targets can be achieved only on the north and south façades, and accordingly the adaptive design option shall be implemented on the east and west façades. Overall, this study contributes to knowledge regarding the optimisation of shading devices in high-rise buildings in the tropics, considering the daylight admission from the four cardinal orientations.
Vaccine Based on Dendritic Cells Electroporated with an Exogenous Ovalbumin Protein and Pulsed with Invariant Natural Killer T Cell Ligands Effectively Induces Antigen-Specific Antitumor Immunity
Authors: Watanabe Akihiro , Yamashita Kimihiro , Fujita Mitsugu , Arimoto Akira , Nishi Masayasu , Takamura Shiki , Saito Masafumi , Yamada Kota , Agawa Kyosuke , Mukoyama Tomosuke , Ando Masayuki , Kanaji Shingo , Matsuda Takeru , Oshikiri Taro , Kakeji Yoshihiro
Published: December 2021

(1) Background: Cancer vaccines are administered to induce cytotoxic CD8+ T cells (CTLs) specific for tumor antigens. Invariant natural killer T (iNKT) cells, the specific T cells activated by α-galactosylceramide (α-GalCer), play important roles in this process as they are involved in both innate and adaptive immunity. We developed a new cancer vaccine strategy in which dendritic cells (DCs) were loaded with an exogenous ovalbumin (OVA) protein by electroporation (EP) and pulsed with α-GalCer. (2) Methods: We generated bone marrow-derived DCs from C57BL/6 mice, loaded full-length ovalbumin proteins to the DCs by EP, and pulsed them with α-GalCer (OVA-EP-galDCs). The OVA-EP-galDCs were intravenously administered to C57BL/6 mice as a vaccine. We then investigated subsequent immune responses, such as the induction of iNKT cells, NK cells, intrinsic DCs, and OVA-specific CD8+ T cells, including tissue-resident memory T (TRM) cells. (3) Results: The OVA-EP-galDC vaccine efficiently rejected subcutaneous tumors in a manner primarily dependent on CD8+ T cells. In addition to the OVA-specific CD8+ T cells both in early and late phases, we observed the induction of antigen-specific TRM cells in the skin. (4) Conclusions: The OVA-EP-galDC vaccine efficiently induced antigen-specific antitumor immunity, which was sustained over time, as shown by the TRM cells.
Preoperative Nodal US Features for Predicting Recurrence in N1b Papillary Thyroid Carcinoma
Authors: Eun Na Lae , Kim Jeong-Ah , Gweon Hye Mi , Youk Ji Hyun , Son Eun Ju
Published: December 2021

This study aimed to investigate whether preoperative ultrasonographic (US) features of metastatic lymph nodes (LNs) are associated with tumor recurrence in patients with N1b papillary thyroid carcinoma (PTC). We enrolled 692 patients (mean age, 41.9 years; range, 6–80 years) who underwent total thyroidectomy and lateral compartment LN dissection between January 2009 and December 2015 and were followed-up for 12 months or longer. Clinicopathologic findings and US features of the index tumor and metastatic LNs in the lateral neck were reviewed. A Kaplan-Meier analysis and Cox proportion hazard model were used to analyze the recurrence-free survival rates and features associated with postoperative recurrence. Thirty-seven (5.3%) patients had developed recurrence at a median follow-up of 66.5 months. On multivariate Cox proportional hazard analysis, male sex (hazard ratio [HR], 2.277; 95% confidence interval [CI]: 1.131, 4.586; p = 0.021), age ≥55 years (HR, 3.216; 95% CI: 1.529, 6.766; p = 0.002), LN size (HR, 1.054; 95% CI: 1.024, 1.085; p < 0.001), and hyperechogenicity of LN (HR, 8.223; 95% CI: 1.689, 40.046; p = 0.009) on US were independently associated with recurrence. Preoperative US features of LNs, including size and hyperechogenicity, may be valuable for predicting recurrence in patients with N1b PTC.
Salvage Therapy for Relapsed Malignant Pleural Mesothelioma: A Systematic Review and Network Meta-Analysis
Authors: Tsai Yu-Chen , Chen Hsiao-Ling , Lee Tai-Huang , Chang Hsiu-Mei , Wu Kuan-Li , Chuang Cheng-Hao , Chang Yong-Chieh , Tu Yu-Kang , Hung Jen-Yu , Yang Chih-Jen , Chong Inn-Wen
Published: December 2021

Patients with malignant pleural mesothelioma (MPM) have very poor prognoses, and pemetrexed plus platinum is the standard first-line therapy. However, the second-line therapy for relapsed MPM remains controversial. A comprehensive search was performed to identify randomized controlled trials (RCTs) evaluating various second-line regimens in patients with relapsed MPM. Indirect comparisons of overall survival (OS) and progression-free survival (PFS) were performed using network meta-analysis. Surface under the cumulative ranking curve (SUCRA) values were used to rank the included treatments according to each outcome. Nivolumab alone or nivolumab plus ipilimumab provided significantly longer OS than placebo (hazard ratio (HR): 0.72, 95% confidence interval (CI): 0.55–0.94 for nivolumab alone; HR: 0.54, 95% CI: 0.31–0.92 for nivolumab plus ipilimumab). The best SUCRA ranking for OS was identified for nivolumab plus ipilimumab (SUCRA: 90.8%). Tremelimumab, vorinostat, nivolumab alone, chemotherapy (CTX), asparagine–glycine–arginine–human tumor necrosis factor plus CTX, and nivolumab plus ipilimumab all produced noticeable PFS benefits compared with placebo. Nivolumab plus ipilimumab had the best PFS ranking (SUCRA: 92.3%). Second-line treatment with nivolumab plus ipilimumab provided the OS and PFS outcomes for patients with relapsed MPM.
Covering the Role of PGC-1α in the Nervous System
Authors: Kuczynska Zuzanna , Metin Erkan , Liput Michal , Buzanska Leonora
Published: December 2021

The peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a well-known transcriptional coactivator involved in mitochondrial biogenesis. PGC-1α is implicated in the pathophysiology of many neurodegenerative disorders; therefore, a deep understanding of its functioning in the nervous system may lead to the development of new therapeutic strategies. The central nervous system (CNS)-specific isoforms of PGC-1α have been recently identified, and many functions of PGC-1α are assigned to the particular cell types of the central nervous system. In the mice CNS, deficiency of PGC-1α disturbed viability and functioning of interneurons and dopaminergic neurons, followed by alterations in inhibitory signaling and behavioral dysfunction. Furthermore, in the ALS rodent model, PGC-1α protects upper motoneurons from neurodegeneration. PGC-1α is engaged in the generation of neuromuscular junctions by lower motoneurons, protection of photoreceptors, and reduction in oxidative stress in sensory neurons. Furthermore, in the glial cells, PGC-1α is essential for the maturation and proliferation of astrocytes, myelination by oligodendrocytes, and mitophagy and autophagy of microglia. PGC-1α is also necessary for synaptogenesis in the developing brain and the generation and maintenance of synapses in postnatal life. This review provides an outlook of recent studies on the role of PGC-1α in various cells in the central nervous system.
Impaired Glucocorticoid Receptor Signaling Aggravates Lung Injury after Hemorrhagic Shock
Authors: Preuss Jonathan M. , Burret Ute , Gröger Michael , Kress Sandra , Scheuerle Angelika , Möller Peter , Tuckermann Jan P. , Wepler Martin , Vettorazzi Sabine
Published: December 2021

We previously showed that attenuated lung injury after hemorrhagic shock (HS) coincided with enhanced levels of the glucocorticoid (GC) receptor (GR) in lung tissue of swine. Here, we investigated the effects of impaired GR signaling on the lung during resuscitated HS using a dysfunctional GR mouse model (GRdim/dim). In a mouse intensive care unit, HS led to impaired lung mechanics and aggravated lung inflammation in GRdim/dim mice compared to wildtype mice (GR+/+). After HS, high levels of the pro-inflammatory and pro-apoptotic transcription factor STAT1/pSTAT1 were found in lung samples from GRdim/dim mice. Lungs of GRdim/dim mice revealed apoptosis, most likely as consequence of reduced expression of the lung-protective Angpt1 compared to GR+/+ after HS. RNA-sequencing revealed increased expression of pro-apoptotic and cytokine-signaling associated genes in lung tissue of GRdim/dim mice. Furthermore, high levels of pro-inflammatory cytokines and iNOS were found in lungs of GRdim/dim mice. Our results indicate impaired repression of STAT1/pSTAT1 due to dysfunctional GR signaling in GRdim/dim mice, which leads to increased inflammation and apoptosis in the lungs. These data highlight the crucial role of functional GR signaling to attenuate HS-induced lung damage.
Exogenous and Endogenous Dendritic Cell-Derived Exosomes: Lessons Learned for Immunotherapy and Disease Pathogenesis
Authors: Elashiry Mahmoud , Elsayed Ranya , Cutler Christopher W.
Published: December 2021

Immune therapeutic exosomes, derived exogenously from dendritic cells (DCs), the ‘directors’ of the immune response, are receiving favorable safety and tolerance profiles in phase I and II clinical trials for a growing number of inflammatory and neoplastic diseases. DC-derived exosomes (EXO), the focus of this review, can be custom tailored with immunoregulatory or immunostimulatory molecules for specific immune cell targeting. Moreover, the relative stability, small size and rapid uptake of EXO by recipient immune cells offer intriguing options for therapeutic purposes. This necessitates an in-depth understanding of mechanisms of EXO biogenesis, uptake and routing by recipient immune cells, as well as their in vivo biodistribution. Against this backdrop is recognition of endogenous exosomes, secreted by all cells, the molecular content of which is reflective of the metabolic state of these cells. In this regard, exosome biogenesis and secretion is regulated by cell stressors of chronic inflammation and tumorigenesis, including dysbiotic microbes, reactive oxygen species and DNA damage. Such cell stressors can promote premature senescence in young cells through the senescence associated secretory phenotype (SASP). Pathological exosomes of the SASP amplify inflammatory signaling in stressed cells in an autocrine fashion or promote inflammatory signaling to normal neighboring cells in paracrine, without the requirement of cell-to-cell contact. In summary, we review relevant lessons learned from the use of exogenous DC exosomes for immune therapy, as well as the pathogenic potential of endogenous DC exosomes.