bluuebunny/crossref_metadata_2025 huggingface dataset:
A Feature Fusion Model with Data Augmentation for Speech Emotion Recognition
Authors: Tu Zhongwen , Liu Bin , Zhao Wei , Yan Raoxin , Zou Yang
Published: March 2023

The Speech Emotion Recognition (SER) algorithm, which aims to analyze the expressed emotion from a speech, has always been an important topic in speech acoustic tasks. In recent years, the application of deep-learning methods has made great progress in SER. However, the small scale of the emotional speech dataset and the lack of effective emotional feature representation still limit the development of research. In this paper, a novel SER method, combining data augmentation, feature selection and feature fusion, is proposed. First, aiming at the problem that there are inadequate samples in the speech emotion dataset and the number of samples in each category is unbalanced, a speech data augmentation method, Mix-wav, is proposed which is applied to the audio of the same emotion category. Then, on the one hand, a Multi-Head Attention mechanism-based Convolutional Recurrent Neural Network (MHA-CRNN) model is proposed to further extract the spectrum vector from the Log-Mel spectrum. On the other hand, Light Gradient Boosting Machine (LightGBM) is used for feature set selection and feature dimensionality reduction in four emotion global feature sets, and more effective emotion statistical features are extracted for feature fusion with the previously extracted spectrum vector. Experiments are carried out on the public dataset Interactive Emotional Dyadic Motion Capture (IEMOCAP) and Chinese Hierarchical Speech Emotion Dataset of Broadcasting (CHSE-DB). The experiments show that the proposed method achieves 66.44% and 93.47% of the unweighted average test accuracy, respectively. Our research shows that the global feature set after feature selection can supplement the features extracted by a single deep-learning model through feature fusion to achieve better classification accuracy.
Preventive Effects of Chlorogenic Acid on Alveolar Bone Loss in Ligature-Induced Periodontitis in Mice
Authors: Nishida Yuka , Shimada Katsumitsu , Horibe Kanji , Seki Kousuke , Murai Yoshinori , Sogawa Chiharu , Murakami Satoshi , Nakamura Hiroaki , Masuda Yuji , Sogawa Norio
Published: March 2023

Chlorogenic acid (CGA) is a polyphenol that is present in coffee beans, many vegetables, and fruits. Since CGA has been reported to exert antioxidant and anti-inflammatory effects, it is expected to protect against periodontitis. In the present study, we used a ligature-induced experimental periodontitis model and investigated the beneficial effects of CGA against alveolar bone resorption caused by experimental periodontitis. To examine the inhibitory effects of CGA on bone loss, a ligature was wrapped around the maxillary right second molar, and CGA was intraperitoneally injected once a day for 2 weeks. In another experiment to investigate the restorative effects of CGA on bone loss, a ligature was wrapped around the maxillary right second molar for 2 weeks, it was then removed, and CGA was intraperitoneally injected once a day for 2 weeks. At the end of the experiments, the maxillae were removed, and CT images were taken. Alveolar bone loss was measured as the distance from the cement–enamel junction to the alveolar crest. The statistical analysis was performed using GraphPad Prism6 (Dunn’s multiple comparison test). The results revealed that the ratio of the buccal alveolar bone loss (vs. the bone loss on the nonligated side) induced by ligation was significantly decreased by the administration of CGA (5 mg/kg) for 2 weeks. Moreover, the bone loss ratio on the buccal and palatal sides after 2 weeks of ligation was significantly decreased by the 2-week administration of CGA (5 mg/kg). The present results revealed that CGA exerted preventive effects against alveolar bone loss caused by experimental periodontitis.
A Probabilistic Forecast Algorithm of Nonconvective Turbulence over the Tibetan Plateau
Authors: Shen Dongdong , Ran Lingkun , Tian Liqing , Zhou Kuo , Tang Jiahui
Published: March 2023

The development of upper-level turbulence forecast algorithms is important for enhancing flight safety. Seventeen nonconvective turbulence indices were calculated over the Tibetan Plateau for August from 2012–2021 with ERA5 reanalysis data. The thresholds for these turbulence indices were reclassified by using the percentile method based on the Richardson number. The reclassified thresholds were found to be more reasonable than the empirical thresholds. A turbulence probability index was used to aggregate the 17 turbulence indices without requiring observational data. The validity of the turbulence probability index was preliminarily confirmed by comparing it with turbulence events. Further research revealed that the turbulence probability index exhibited interannual fluctuation.
Special Issue on Unmanned Aerial Vehicles
Authors: Bertrand Sylvain , Shin Hyo-Sang
Published: March 2023

Unmanned Aerial Vehicles (UAVs) are recognized as very useful tools to replace, help, or assist humans in various missions, such as inspection and monitoring, surveillance, search and rescue, exploration, logistics and transportation, etc [...]
Dynamics of a Flexible Roof Test Model under Ambient Vibrations Measurements
Authors: Rizzo Fabio , Bedon Chiara , Mansour Sulyman , Pistol Aleksander , Sabbà Maria Francesca , Flaga Łukasz , Klaput Renata , Foti Dora
Published: March 2023

Flexible roofs are sensitive to wind actions because they are light, and their deformability can induce local or global instability. In most cases, their design requires experimental wind tunnel testing to investigate the aeroelastic phenomena and the structural response under the wind. However, the reduced scale necessary in wind tunnels makes the dynamic identification of the test model difficult. Several approaches of multi-modal dynamic identification can be used, even if a specific approach is not defined for geometric nonlinear flexible roofs. Many times, the choice of the position of the sensors is affected by the unknown roof dynamics. This paper investigates the ambient vibration time-dependent accelerations for a flexible roof scaled model through Singular Value Decomposition (SVD) and their spatial correlations with the purpose of analyzing the signal structure and its acquisition to perform the dynamic identification of the test model.
Numerical Design and Optimisation of Self-Compacting High Early-Strength Cement-Based Mortars
Authors: Cangussu Nara , Matos Ana Mafalda , Milheiro-Oliveira Paula , Maia Lino
Published: March 2023

The use of SCC in Europe began in the 1990s and was mainly promoted by the precast industry. Precast companies generally prefer high early-strength concrete mixtures to accelerate their production rate, reducing the demoulding time. From a materials science point of view, self-compacting and high early-strength concrete mixes may be challenging because they present contradicting mixture design requirements. For example, a low water/binder ratio (w/b) is key to achieving high early strength. However, it may impact the self-compacting ability, which is very sensitive to Vw/Vp. As such, the mixture design can be complex. The design of the experimental approach is a powerful tool for designing, predicting, and optimising advanced cement-based materials when several constituent materials are employed and multi-performance requirements are targeted. The current work aimed at fitting models to mathematically describe the flow ability, viscosity, and mechanical strength properties of high-performance self-compacting cement-based mortars based on a central composite design. The statistical fitted models revealed that Vs/Vm exhibited the strongest (negative) effect on the slump-flow diameter and T-funnel time. Vw/Vp showed the most significant effect on mechanical strength. Models were then used for mortar optimisation. The proposed optimal mixture represents the best compromise between self-compacting ability—a flow diameter of 250 mm and funnel time equal to 10 s—and compressive strength higher than 50 MPa at 24 h without any special curing treatment.
FPGA Implementation of a Deep Learning Acceleration Core Architecture for Image Target Detection
Authors: Yang Xu , Zhuang Chen , Feng Wenquan , Yang Zhe , Wang Qiang
Published: March 2023

Due to the flexibility and ease of deployment of Field Programmable Gate Arrays (FPGA), more and more studies have been conducted on developing and optimizing target detection algorithms based on Convolutional Neural Networks (CNN) models using FPGAs. Still, these studies focus on improving the performance of the core algorithm and optimizing hardware structure, with few studies focusing on the unified architecture design and corresponding optimization techniques for the algorithm model, resulting in inefficient overall model performance. The essential reason is that these studies do not address arithmetic power, speed, and resource consistency. In order to solve this problem, we propose a deep learning acceleration core architecture based on FPGAs, which is designed for target detection algorithms with CNN models, using multi-channel parallelization of CNN network models to improve the arithmetic power, using scheduling tasks and intensive computation pipelining to meet the algorithm’s data bandwidth requirements and unifying the speed and area of the orchestrated computation matrix to save hardware resources. The proposed framework achieves 14 Frames Per Second (FPS) inference performance of the TinyYolo model at 5 Giga Operations Per Second (GOPS) with 30% higher running clock frequency, 2–4 times higher arithmetic power, and 28% higher Digital Signal Processing (DSP) resource utilization efficiency using less than 25% of FPGA resource usage.
Prediction Analysis of Surface Roughness of Aluminum Al6061 in End Milling CNC Machine Using Soft Computing Techniques
Authors: Balonji Serge , Tartibu Lagouge K. , Okokpujie Imhade P.
Published: March 2023

Computer numerically controlled (CNC) milling has been one of the most commonly used manufacturing processes for the performance of multiple operations, from tiny integrated circuits to heavy-duty mining machine gearboxes. It is a well-known machining process that offers close tolerances and repeated operations. However, the choice of machining parameters to achieve a desired part’s surface roughness (SR) remains a challenge. In the present study, artificial neural network (ANN) and adaptive network-based fuzzy inference system (ANFIS) approaches have been used to predict and monitor the surface roughness of aluminum Al6061 machined blocks. Furthermore, both models have been hybridized with genetic algorithm (GA) and particle swarm optimization (PSO) to investigate the potential enhancement in the prediction performance of the hybrid approach. The results show that factors such as the population size, the acceleration values, the choice of membership functions, and the number of neurons and layers significantly influence the prediction performance of the proposed models. Through a parametric analysis, this study demonstrates how the configuration of the models could affect the prediction performance. While exhibiting the impact of models’ hyperparameter combination on the prediction ability, this study provides insight into the development of suitable prediction models and the potential of soft computing techniques to predict the surface roughness of aluminum Al6061 blocks on CNC machines.
A Focused Event Crawler with Temporal Intent
Authors: Wu Hao , Hou Dongyang
Published: March 2023

Temporal intent is an important component of events. It plays an important role in collecting them from the web with focused crawlers. However, traditionally focused crawlers usually only consider factors such as topic keywords, web page content, and anchor text, ignoring the relationship between web pages and the temporal intent of events. This leads to their poor crawling performance. This paper aims to understand the temporal intent of events and apply it within focused crawlers. First, a new temporal intent identification method is proposed based on Google Trends data. The method can automatically identify the start time of an event and quantify the temporal distribution of the event. Then, a new focused event crawler with temporal intent is proposed. The crawler incorporates the start time of the event into the similarity calculation module, and a new URL (Uniform Resource Locator) priority assignment method is developed using the quantified temporal distribution of temporal intent as the independent variable of a natural exponential function. Experimental results show that our method is effective in identifying the start time of events at the month level and quantifying the temporal distribution of events. Furthermore, compared to the traditional best-first crawling method, the precision of our method improves by an average of 10.28%, and a maximum of 25.21%. These results indicate that our method performs better in retrieving relevant pages and assigning URL priority. This also illustrates the importance of the relationship between web pages and the temporal intent of events.
Design and Reliability Analysis of a Series/Parallel Hybrid System with a Rotary Engine for Safer Ultralight Aviation
Authors: Donateo Teresa , Spada Chiodo Ludovica
Published: March 2023

The conventional powertrain for ultralight aviation consists of a fixed pitch propeller connected to an internal combustion engine (ICE). Since ICEs have a limited thermal efficiency (<40%), new and more efficient powerplant configurations have recently been proposed in the scientific literature by adopting hybrid electric solutions. Hybridization has the additional benefit of increased safety thanks to redundancy. This is a very important issue in ultralight aviation, where a high percentage of accidents are caused by engine failure. In a previous investigation, the authors proposed the design of a series/parallel hybrid electric power system to increase safety and optimize fuel economy by controlling the engine working points during flight. A new powertrain, derived from an automotive Honda i-MMD system, is analyzed in this study and a reliability analysis is performed to underline the improved safety obtained with the proposed system.
An In-Depth Review of the Benefits of Antibiotic Use in the Treatment of Borreliosis in Pregnancy
Authors: Cook Michael J. , Moynan David , Avramovic Gordana , Lambert John S.
Published: March 2023

Evidence of congenital transmission of Lyme disease from mother to fetus has been investigated since the 1980s. This study reports the results of a retrospective analysis of 31 studies described in 27 papers published in a 2018 review article. Analysis of these identified statistically probable transmission in 13 (42%) of the 31 studies and possible transmission in 2 (6%). Most studies included mothers who had been treated with antimicrobials. When no antimicrobials were used, 74% of the pregnancies had adverse outcomes. When oral antimicrobials were used, 29% of pregnancies had adverse outcomes. When intravenous (IV) antimicrobials were used, adverse outcomes dropped to 12% of the pregnancies. This is a six-fold reduction in risk compared with no antimicrobial treatment. Some studies did not define whether oral or IV antimicrobials were used. When these results were included, adverse outcomes were 30 times higher for untreated mothers. Adverse outcomes included deaths, heart anomalies, and preterm births.
The Intersection of Abstract Expressionist and Mass Visual Culture—An Historiographic Overview
Authors: Gilbert Gregory
Published: March 2023

Of the major modernist movements in the 20th century, Abstract Expressionism long retained its canonical status as a radical avant-garde detached from a broader mass culture [...]
Fugitive Emissions from Mobile Sources—Experimental Analysis in Buses Regulated by the Euro 5 Standard
Authors: Caetano Antonio C. , da Costa Alexandre M. S. da , Janeiro Vanderly , Soares Paulo H. , Cancino Leonel R. , Andrade Cid M. G.
Published: March 2023

Fugitive emissions are unintentionally produced by pipeline leakage and evaporation in industrial processes and contribute 5% of Global Greenhouse Gas emissions (GHG). Frictional wear and thermal fatigue in vehicle exhaust pipe couplings and joints can cause leaks that are not visible and difficult to quantify. It is therefore essential to trace and document these sources. In this work, an experimental survey was conducted on buses in accordance with Regulation (EC) N° 715/2007 of the European Parliament. Statistical methods by means of a priori analysis aided by G∗Power 3.1 software was used to define the required sample. Three random sample groups were stratified and fugitive gases were encased and piped into a bronze tube 5 mm in diameter and 500 mm in length. A Horiba PG-300 analyzer was used to analyze the samples using chemiluminescence and infrared methods. The results proved the existence of fugitive emissions in all samples analyzed with variations of (3.000–27.500 ppm) among the samples for CO2, (6.0–138.5 ppm) and (2.0–5.0 ppm) for CO and NOx, respectively. Statistical analysis showed that engine mileage had no significant influence on NOx emissions, while CO and CO2 emissions increased with mileage. Analysis using Response Surface Methodology (RSM) indicated a trend of increasing concentrations of CO2 and CO for both explanatory variables, mileage and usage time.
Applications of CNOP-P Method to Predictability Studies of Terrestrial Ecosystems
Authors: Sun Guodong , Mu Mu
Published: March 2023

In this paper, recent research on terrestrial ecosystem predictability using the conditional nonlinear optimal parameter perturbation (CNOP-P) method is summarized. The main findings include the impacts of uncertainties in climate change on uncertainties in simulated terrestrial ecosystems, the identification of key physical parameters that lead to large uncertainties in terrestrial ecosystem modeling and prediction, and the evaluation of the simulation ability and prediction skill of terrestrial ecosystems by reducing key physical parameter errors. The study areas included the Inner Mongolia region, north–south transect of eastern China, and Qinghai–Tibet Plateau region. The periods of the studies were from 1961 to 1970 for the impacts of uncertainties in climate change on uncertainties in simulated terrestrial ecosystems, and from 1951 to 2000 for the identification of the most sensitive combinations of physical parameters. Climatic Research Unit (CRU) data were employed. The numerical results indicate the important role of nonlinear changes in climate variability due to the occurrences of extreme events characterized by CNOP-P in the abrupt grassland ecosystem equilibrium state and formation of carbon sinks in China. Second, the most sensitive combinations of physical parameters to the uncertainties in simulations and predictions of terrestrial ecosystems identified by the CNOP-P method were more sensitive than those obtained by traditional methods (e.g., one-at-a-time (OAT) and stochastic methods). Furthermore, the improvement extent of the simulation ability and prediction skill of terrestrial ecosystems by reducing the errors of the sensitive physical parameter combinations identified by the CNOP-P method was higher than that by the traditional methods.
Comparative Study with Applications for Gompertz Models under Competing Risks and Generalized Hybrid Censoring Schemes
Authors: Al-Essa Laila A. , Soliman Ahmed A. , Abd-Elmougod Gamal A. , Alshanbari Huda M.
Published: March 2023

In reliability and survival analysis, the time-to-failure data play an important role in the development of the reliability and life characteristics of the products. In some cases, these kinds of data are modeled using a competing risks model. The problem of conducting comparative life testing under a competing risks model when the units come from different lines of production has recently been addressed. In this paper, we address this problem when the life of the unit is distributed using the Gompertz distribution, noting that the units come from two lines of production and two independent causes of failure are activated. The data are collected under a joint generalized type-II hybrid censoring scheme. Maximum likelihood estimators of the unknown parameters are derived, along with the corresponding asymptotic confidence intervals. We also adopt two bootstrap confidence intervals. Using independent gamma priors, the Bayes estimators relative to squared error loss function are obtained with credible intervals. The properties and quality of estimators are measured by performing a Monte Carlo simulation study. Finally, a real-life data set is analyzed to discuss the applicability of the proposed methods to real phenomena. The optimal plan with respect to comments on the numerical results is discussed in the conclusion.
Interface Engineering of a NASICON-Type Electrolyte Using Ultrathin CuS Film for Lithium Metal Batteries
Authors: Zhang Shengnan , Liu Dongming , Zhang Lin , Li Jianwei , Zhao Guoqing , Ci Lijie , Min Guanghui
Published: March 2023

NASICON-type Li1.5Al0.5Ge1.5(PO4)3 (LAGP) is a remarkable solid-state electrolyte due to its high ionic conductivity and excellent air stability. However, the weak LAGP|Li interfacial compatibility (e.g., chemical instability of LAGP with Li metal and lithium dendrite growth) limits its practical application. Herein, an ultrathin CuS layer was fabricated on the surface of the LAGP electrolyte by magnetron sputtering (MS). Then, an in situ Li2S/Cu nano-layer formed via the conversion reaction between CuS and molten Li was constructed at the LAGP|Li interface. The Li2S/Cu nano-layer enables effective hindering of the reduction reactions of LAGP with Li metals and the suppression of lithium dendrite growth. The assembled Li symmetric battery with the Li2S/Cu@LAGP electrolyte shows a promising critical current density (CCD) of 0.6 mA cm−2 and a steady battery operation for over 700 h. Furthermore, the full LiFePO4 battery comprising the Li2S/Cu@LAGP electrolyte shows excellent capacity retention of 94.5% after 100 cycles, providing an appropriate interface modification strategy for all-solid-state Li metal batteries.
Intelligent Multi-Lingual Cyber-Hate Detection in Online Social Networks: Taxonomy, Approaches, Datasets, and Open Challenges
Authors: Gamal Donia , Alfonse Marco , Jiménez-Zafra Salud María , Aref Mostafa
Published: March 2023

Sentiment Analysis, also known as opinion mining, is the area of Natural Language Processing that aims to extract human perceptions, thoughts, and beliefs from unstructured textual content. It has become a useful, attractive, and challenging research area concerning the emergence and rise of social media and the mass volume of individuals’ reviews, comments, and feedback. One of the major problems, apparent and evident in social media, is the toxic online textual content. People from diverse cultural backgrounds and beliefs access Internet sites, concealing and disguising their identity under a cloud of anonymity. Due to users’ freedom and anonymity, as well as a lack of regulation governed by social media, cyber toxicity and bullying speech are major issues that need an automated system to be detected and prevented. There is diverse research in different languages and approaches in this area, but the lack of a comprehensive study to investigate them from all aspects is tangible. In this manuscript, a comprehensive multi-lingual and systematic review of cyber-hate sentiment analysis is presented. It states the definition, properties, and taxonomy of cyberbullying and how often each type occurs. In addition, it presents the most recent popular cyberbullying benchmark datasets in different languages, showing their number of classes (Binary/Multiple), discussing the applied algorithms, and how they were evaluated. It also provides the challenges, solutions, as well as future directions.
Woven Vascular Stent-Grafts with Surface Modification of Silk Fibroin-Based Paclitaxel/Metformin Microspheres
Authors: Liang Mengdi , Li Fang , Wang Yongfeng , Chen Hao , Tian Jingjing , Zhao Zeyu , Schneider Karl H. , Li Gang
Published: March 2023

In-stent restenosis caused by tumor ingrowth increases the risk of secondary surgery for patients with abdominal aortic aneurysms (AAA) because conventional vascular stent grafts suffer from mechanical fatigue, thrombosis, and endothelial hyperplasia. For that, we report a woven vascular stent-graft with robust mechanical properties, biocompatibility, and drug delivery functions to inhibit thrombosis and the growth of AAA. Paclitaxel (PTX)/metformin (MET)-loaded silk fibroin (SF) microspheres were self-assembly synthesized by emulsification-precipitation technology and layer-by-layer coated on the surface of a woven stent via electrostatic bonding. The woven vascular stent-graft before and after coating drug-loaded membranes were characterized and analyzed systematically. The results show that small-sized drug-loaded microspheres increased the specific surface area and promoted the dissolution/release of drugs. The stent-grafts with drug-loaded membranes exhibited a slow drug-release profile more for than 70 h and low water permeability at 158.33 ± 17.56 mL/cm2·min. The combination of PTX and MET inhibited the growth of human umbilical vein endothelial cells. Therefore, it was possible to generate dual-drug-loaded woven vascular stent-grafts to achieve the more effective treatment of AAA.
A Review of the Technology, Training, and Assessment Methods for the First Real-Time AI-Enhanced Medical Device for Endoscopy
Authors: Cherubini Andrea , Dinh Nhan Ngo
Published: March 2023

Artificial intelligence (AI) has the potential to assist in endoscopy and improve decision making, particularly in situations where humans may make inconsistent judgments. The performance assessment of the medical devices operating in this context is a complex combination of bench tests, randomized controlled trials, and studies on the interaction between physicians and AI. We review the scientific evidence published about GI Genius, the first AI-powered medical device for colonoscopy to enter the market, and the device that is most widely tested by the scientific community. We provide an overview of its technical architecture, AI training and testing strategies, and regulatory path. In addition, we discuss the strengths and limitations of the current platform and its potential impact on clinical practice. The details of the algorithm architecture and the data that were used to train the AI device have been disclosed to the scientific community in the pursuit of a transparent AI. Overall, the first AI-enabled medical device for real-time video analysis represents a significant advancement in the use of AI for endoscopies and has the potential to improve the accuracy and efficiency of colonoscopy procedures.
Physiological, Nutritional and Transcriptomic Responses of Sturgeon (Acipenser schrenckii) to Complete Substitution of Fishmeal with Cottonseed Protein Concentrate in Aquafeed
Authors: Wang Chang’an , Zhao Zhigang , Lu Shaoxia , Liu Yang , Han Shicheng , Jiang Haibo , Yang Yuhong , Liu Hongbai
Published: March 2023

This study estimated the effect of substituting fishmeal completely with cottonseed protein concentrate (CPC) in the diet of sturgeon (Acipenser schrenckii) on growth, digestive physiology, and hepatic gene expression. A control diet containing fishmeal and an experimental diet based on CPC was designed. The study was conducted for 56 days in indoor recirculating aquaculture systems. The results showed that weight gain, feed efficiency, and whole-body essential amino acids (EAAs) all decreased significantly in the experimental group, while whole-body non-essential amino acids (NEAAs) and serum transaminase activity increased (p < 0.05). The activity of digestive enzymes in the mid-intestine was significantly reduced (p < 0.05), and liver histology revealed fatty infiltration of hepatocytes. The hepatic transcriptome revealed an upregulation of genes linked to metabolism, including steroid biosynthesis, pyruvate metabolism, fatty acid metabolism, and amino acid biosynthesis. These findings indicate that fully replacing fishmeal with CPC harms A. schrenckii growth and physiology. This study provides valuable data for the development of improved aquafeeds and the use of molecular methods to evaluate the diet performance of sturgeon.
Inherited Retinal Degeneration: Towards the Development of a Combination Therapy Targeting Histone Deacetylase, Poly (ADP-Ribose) Polymerase, and Calpain
Authors: Dong Yujie , Yan Jie , Yang Ming , Xu Wenrong , Hu Zhulin , Paquet-Durand François , Jiao Kangwei
Published: March 2023

Inherited retinal degeneration (IRD) represents a diverse group of gene mutation-induced blinding diseases. In IRD, the loss of photoreceptors is often connected to excessive activation of histone-deacetylase (HDAC), poly-ADP-ribose-polymerase (PARP), and calpain-type proteases (calpain). Moreover, the inhibition of either HDACs, PARPs, or calpains has previously shown promise in preventing photoreceptor cell death, although the relationship between these enzyme groups remains unclear. To explore this further, organotypic retinal explant cultures derived from wild-type mice and rd1 mice as a model for IRD were treated with different combinations of inhibitors specific for HDAC, PARP, and calpain. The outcomes were assessed using in situ activity assays for HDAC, PARP, and calpain, immunostaining for activated calpain-2, and the TUNEL assay for cell death detection. We confirmed that inhibition of either HDAC, PARP, or calpain reduced rd1 mouse photoreceptor degeneration, with the HDAC inhibitor Vorinostat (SAHA) being most effective. Calpain activity was reduced by inhibition of both HDAC and PARP whereas PARP activity was only reduced by HDAC inhibition. Unexpectedly, combined treatment with either PARP and calpain inhibitors or HDAC and calpain inhibitors did not produce synergistic rescue of photoreceptors. Together, these results indicate that in rd1 photoreceptors, HDAC, PARP, and calpain are part of the same degenerative pathway and are activated in a sequence that begins with HDAC and ends with calpain.
Exploring the Role of PI3P in Platelets: Insights from a Novel External PI3P Pool
Authors: Mujalli Abdulrahman , Viaud Julien , Severin Sonia , Gratacap Marie-Pierre , Chicanne Gaëtan , Hnia Karim , Payrastre Bernard , Terrisse Anne-Dominique
Published: March 2023

Phosphoinositides (PIs) play a crucial role in regulating intracellular signaling, actin cytoskeleton rearrangements, and membrane trafficking by binding to specific domains of effector proteins. They are primarily found in the membrane leaflets facing the cytosol. Our study demonstrates the presence of a pool of phosphatidylinositol 3-monophosphate (PI3P) in the outer leaflet of the plasma membrane of resting human and mouse platelets. This pool of PI3P is accessible to exogenous recombinant myotubularin 3-phosphatase and ABH phospholipase. Mouse platelets with loss of function of class III PI 3-kinase and class II PI 3-kinase α have a decreased level of external PI3P, suggesting a contribution of these kinases to this pool of PI3P. After injection in mouse, or incubation ex vivo in human blood, PI3P-binding proteins decorated the platelet surface as well as α-granules. Upon activation, these platelets were able to secrete the PI3P-binding proteins. These data sheds light on a previously unknown external pool of PI3P in the platelet plasma membrane that recognizes PI3P-binding proteins, leading to their uptake towards α-granules. This study raises questions about the potential function of this external PI3P in the communication of platelets with the extracellular environment, and its possible role in eliminating proteins from the plasma.
Bacteriophages of the Order Crassvirales: What Do We Currently Know about This Keystone Component of the Human Gut Virome?
Authors: Smith Linda , Goldobina Ekaterina , Govi Bianca , Shkoporov Andrey N.
Published: March 2023

The order Crassvirales comprises dsDNA bacteriophages infecting bacteria in the phylum Bacteroidetes that are found in a variety of environments but are especially prevalent in the mammalian gut. This review summarises available information on the genomics, diversity, taxonomy, and ecology of this largely uncultured viral taxon. With experimental data available from a handful of cultured representatives, the review highlights key properties of virion morphology, infection, gene expression and replication processes, and phage-host dynamics.
Evidence That Increasing Serum 25(OH)D Concentrations to 30 ng/mL in the Kingdom of Saudi Arabia and the United Arab Emirates Could Greatly Improve Health Outcomes
Authors: Grant William B. , Al Anouti Fatme , Boucher Barbara J. , Fakhoury Hana M. A. , Moukayed Meis , Pilz Stefan , Al-Daghri Nasser M.
Published: March 2023

Accumulating evidence supports the potential protective effects of vitamin D against chronic diseases such as Alzheimer’s disease, autoimmune diseases, cancers, cardiovascular disease (ischaemic heart disease and stroke), type 2 diabetes, hypertension, chronic kidney disease, stroke, and infectious diseases such as acute respiratory tract diseases, COVID-19, influenza, and pneumonia, as well as adverse pregnancy outcomes. The respective evidence is based on ecological and observational studies, randomized controlled trials, mechanistic studies, and Mendelian randomization studies. However, randomized controlled trials on vitamin D supplementation have largely failed to show benefits, probably due to poor design and analysis. In this work, we aim to use the best available evidence on the potential beneficial effects of vitamin D to estimate the expected reduction in incidence and mortality rates of vitamin D-related diseases in the Kingdom of Saudi Arabia and the United Arab Emirates if minimum serum 25(OH)D concentrations were to be raised to 30 ng/mL. Estimated reductions by 25% for myocardial infarction incidence, 35% for stroke incidence, 20 to 35% for cardiovascular disease mortality, and 35% for cancer mortality rates depicted a promising potential for raising serum 25(OH)D. Methods to increase serum 25(OH)D concentrations at the population level could include food fortification with vitamin D3, vitamin D supplementation, improved dietary vitamin D intake, and sensible sun exposure.
Sulforaphane-Induced Cell Mitotic Delay and Inhibited Cell Proliferation via Regulating CDK5R1 Upregulation in Breast Cancer Cell Lines
Authors: Hung Chao-Ming , Tsai Tai-Hsin , Lee Kuan-Ting , Hsu Yi-Chiang
Published: March 2023

Our research has revealed that sulforaphane (SFN) has chemopreventive properties and could be used in chemotherapy treatments. Further investigation is needed to understand the mechanisms behind sulforaphane’s (SFN) antitumor activity in breast adenocarcinoma, as observed in our studies. This research looked into the effects of SFN on mitosis delay and cell cycle progression in MDA-MB-231 and ZR-75-1 cells, two types of triple-negative breast cancer adenocarcinoma.The proliferation of the cancer cells after SFN exposure was evaluated using MTT assay, DNA content and cell cycle arrest induction by flow cytometry, and expressions of cdc25c, CDK1, cyclin B1 and CDK5R1 were assessed through qRT-PCR and Western blot analysis. SFN was found to inhibit the growth of cancer cells. The accumulation of G2/M-phase cells in SFN-treated cells was attributed to CDK5R1. The disruption of the CDC2/cyclin B1 complex suggested that SFN may have antitumor effects on established breast adenocarcinoma cells. Our findings suggest that, in addition to its chemopreventive properties, SFN could be used as an anticancer agent for breast cancer, as it was found to inhibit growth and induce apoptosis of cancer cells.
Inflammatory Markers as Predictors of Shunt Dependency and Functional Outcome in Patients with Aneurysmal Subarachnoid Hemorrhage
Authors: Rostgaard Nina , Olsen Markus Harboe , Capion Tenna , MacAulay Nanna , Juhler Marianne
Published: March 2023

The mechanisms underlying post-hemorrhagic hydrocephalus (PHH) development following subarachnoid hemorrhage (SAH) are not fully understood, which complicates informed clinical decisions regarding the duration of external ventricular drain (EVD) treatment and prevents the prediction of shunt-dependency in the individual patient. The aim of this study was to identify potential inflammatory cerebrospinal fluid (CSF) biomarkers of PHH and, thus, shunt-dependency and functional outcome in patients with SAH. This study was a prospective observational study designed to evaluate inflammatory markers in ventricular CSF. In total, 31 Patients with SAH who required an EVD between June 2019 and September 2021 at the Department of Neurosurgery, Rigshospitalet, Copenhagen, Denmark, were included. CSF samples were collected twice from each patient and analyzed for 92 inflammatory markers via proximity extension assay (PEA), and the prognostic ability of the markers was investigated. In total, 12 patients developed PHH, while 19 were weaned from their EVD. Their 6-month functional outcome was determined with the modified Rankin Scale. Of the 92 analyzed inflammatory biomarkers, 79 were identified in the samples. Seven markers (SCF, OPG, LAP TGFβ1, Flt3L, FGF19, CST5, and CSF1) were found to be predictors of shunt dependency, and four markers (TNFα, CXCL5, CCL20, and IL8) were found to be predictors of functional outcome. In this study, we identified promising inflammatory biomarkers that are able to predict (i) the functional outcome in patients with SAH and (ii) the development of PHH and, thus, the shunt dependency of the individual patients. These inflammatory markers may have the potential to be employed as predictive biomarkers of shunt dependency and functional outcome following SAH and could, as such, be applied in the clinic.
The Potential of SGLT-2 Inhibitors in the Treatment of Polycystic Ovary Syndrome: The Current Status and Future Perspectives
Authors: Rakic Dejana , Jakovljevic Vladimir , Jovic Nikola , Bicanin Ilic Marija , Dimitrijevic Aleksandra , Vulovic Tatjana , Arsenijevic Petar , Sretenovic Jasmina , Nikolic Maja , Petrovich Fisenko Vladimir , Bolevich Stefani , Zarkovic Gala , Joksimovic Jovic Jovana
Published: March 2023

Polycystic ovary syndrome (PCOS) is the most frequent endocrinopathy during women’s reproductive age. PCOS is a heterogeneous disorder featuring specific cardiometabolic properties. The association between the presence of metabolic disorders and PCOS supports the claim that the regulation of glycemic status is very important in these patients. There is a wide range of therapeutic options (including those treating diabetes mellitus type 2) with potential advantages available for the management of PCOS. Sodium–glucose cotransporter type 2 inhibitors (SGLT-2is) improve glucose metabolism, reduce fat tissue, lower blood pressure, reduce oxidative stress and inflammation, and protect the cardiovascular system. Currently, the use of SGLT-2is is not widespread in PCOS therapy, although these drugs represent a promising new therapeutic approach. Therefore, it is necessary to initiate further study in order to determine more effective therapies for PCOS and investigate the effect of SGLT-2is, both as a monotherapy and in combination with other drugs. It is necessary to understand the mechanisms underlying SGLT-2is in PCOS and their effects on long-term complications, especially since the gold standard treatment for PCOS, such as metformin and oral contraceptives, do not have long-term cardioprotective effects. The effects of SGLT-2is seem to involve cardiac protection, while diminishing endocrine and reproductive abnormalities in PCOS. In the current narrative review, we examine the most recent clinical evidence and discuss the potential applications of SGLT-2is for PCOS therapy.
NLRP3 Inflammasome’s Activation in Acute and Chronic Brain Diseases—An Update on Pathogenetic Mechanisms and Therapeutic Perspectives with Respect to Other Inflammasomes
Authors: Chiarini Anna , Gui Li , Viviani Chiara , Armato Ubaldo , Dal Prà Ilaria
Published: March 2023

Increasingly prevalent acute and chronic human brain diseases are scourges for the elderly. Besides the lack of therapies, these ailments share a neuroinflammation that is triggered/sustained by different innate immunity-related protein oligomers called inflammasomes. Relevant neuroinflammation players such as microglia/monocytes typically exhibit a strong NLRP3 inflammasome activation. Hence the idea that NLRP3 suppression might solve neurodegenerative ailments. Here we review the recent Literature about this topic. First, we update conditions and mechanisms, including RNAs, extracellular vesicles/exosomes, endogenous compounds, and ethnic/pharmacological agents/extracts regulating NLRP3 function. Second, we pinpoint NLRP3-activating mechanisms and known NLRP3 inhibition effects in acute (ischemia, stroke, hemorrhage), chronic (Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, MS, ALS), and virus-induced (Zika, SARS-CoV-2, and others) human brain diseases. The available data show that (i) disease-specific divergent mechanisms activate the (mainly animal) brains NLRP3; (ii) no evidence proves that NLRP3 inhibition modifies human brain diseases (yet ad hoc trials are ongoing); and (iii) no findings exclude that concurrently activated other-than-NLRP3 inflammasomes might functionally replace the inhibited NLRP3. Finally, we highlight that among the causes of the persistent lack of therapies are the species difference problem in disease models and a preference for symptomatic over etiologic therapeutic approaches. Therefore, we posit that human neural cell-based disease models could drive etiological, pathogenetic, and therapeutic advances, including NLRP3’s and other inflammasomes’ regulation, while minimizing failure risks in candidate drug trials.
Epigallocatechin-3-Gallate Prevents the Acquisition of a Cancer Stem Cell Phenotype in Ovarian Cancer Tumorspheres through the Inhibition of Src/JAK/STAT3 Signaling
Authors: Rodriguez Torres Sahily , Gresseau Loraine , Benhamida Meriem , Fernandez-Marrero Yuniel , Annabi Borhane
Published: March 2023

Three-dimensional tumorsphere cultures recapitulate the expression of several cancer stem cell (CSC) biomarkers and represent an effective in vitro platform to screen the anti-CSC properties of drugs. Whereas ovarian carcinoma is among the leading causes of death for women, ovarian CSC (OvCSC), a highly malignant subpopulation of ovarian cancer cells, is thought to be responsible for therapy resistance, metastasis, and tumor relapse. Epigallocatechin-3-gallate (EGCG), a diet-derived active polyphenol found in green tea leaves, can suppress ovarian cancer cell proliferation and induce apoptosis. However, its capacity to prevent the acquisition of cancer stemness traits in ovarian malignancies remains unclear. Here, we exploited the in vitro three-dimensional tumorsphere culture model to explore the capacity of EGCG to alter CSC biomarkers expression, signal transducing events and cell chemotaxis. Total RNA and protein lysates were isolated from human ES-2 ovarian cancer cell tumorspheres for gene assessment by RT-qPCR and protein expression by immunoblot. Real-time cell chemotaxis was assessed with xCELLigence. Compared with their parental adherent cells, tumorspheres expressed increased levels of the CSC markers NANOG, SOX2, PROM1, and Fibronectin. EGCG treatment reduced dose-dependently tumorspheres size and inhibited the transcriptional regulation of those genes. Src and JAK/STAT3 signaling pathways appeared to be relevant for CSC phenotype and chemotactic response. In conclusion, these data highlight and support the chemopreventive benefits of the diet-derived EGCG and its capacity to target intracellular transducing events that regulate the acquisition of an invasive CSC phenotype.
Epidemiology and Outcome of Early-Onset Acute Kidney Injury and Recovery in Critically Ill COVID-19 Patients: A Retrospective Analysis
Authors: Ruault Alice , Philipponnet Carole , Sapin Vincent , Evrard Bertrand , Bouzgarrou Radhia , Calvet Laure , Thouy François , Grapin Kévin , Bonnet Benjamin , Adda Mireille , Souweine Bertrand , Dupuis Claire
Published: March 2023

Background: The clinical significance of early-onset acute kidney injury (EO-AKI) and recovery in severe COVID-19 intensive care unit (ICU) patients is poorly documented. Objective: The aim of the study was to assess the epidemiology and outcome of EO-AKI and recovery in ICU patients admitted for SARS-CoV-2 pneumonia. Design: This was a retrospective single-centre study. Setting: The study was carried out at the medical ICU of the university hospital of Clermont-Ferrand, France. Patients: All consecutive adult patients aged ≥18 years admitted between 20 March 2020 and 31 August 2021 for SARS-CoV-2 pneumonia were enrolled. Patients with chronic kidney disease, referred from another ICU, and with an ICU length of stay (LOS) ≤72 h were excluded. Interventions: EO-AKI was defined on the basis of serum creatinine levels according to the Kidney Disease Improving Global Outcomes criteria, developing ≤7 days. Depending on renal recovery, defined by the normalization of serum creatinine levels, EO-AKI was transient (recovery within 48 h), persistent (recovery between 3 and 7 days) or AKD (no recovery within 7 days after EO-AKI onset). Measurements: Uni- and multivariate analyses were performed to determine factors associated with EO-AKI and EO-AKI recovery. Main Results: EO-AKI occurred in 84/266 (31.5%) study patients, of whom 42 (50%), 17 (20.2%) and 25 (29.7%) had EO-AKI stages 1, 2 and 3, respectively. EO-AKI was classified as transient, persistent and AKD in 40 (47.6%), 15 (17.8%) and 29 (34.6%) patients, respectively. The 90-day mortality was 87/244 (35.6%) and increased with EO-AKI occurrence and severity: no EO-AKI, 38/168 (22.6%); EO-AKI stage 1, 22/39 (56.4%); stage 2, 9/15 (60%); and stage 3, 18/22 (81.8%) (p < 0.01). The 90-day mortality in patients with transient or persistent AKI and AKD was 20/36 (55.6%), 8/14 (57.1%) and 21/26 (80.8%), respectively (p < 0.01). MAKE-90 occurred in 42.6% of all patients. Conclusions: In ICU patients admitted for SARS-CoV-2 pneumonia, the development of EO-AKI and time to recovery beyond day 7 of onset were associated with poor outcome.