bluuebunny/crossref_metadata_2025 huggingface dataset:
Haskap Juicing Method Effects on Haskap Juice Quality
Authors: Wang Zhuoyu , Svyantek Andrej , Miller Zachariah , Jarrett Bridgid , Kapus Ashley
Published: September 2023

This research is the first study on the influence of juicing methods on the ‘Aurora’ haskap juice quality. Three common juice extraction methods, namely, using a steam juicer, a centrifugal juicer, and a bladder wine press, were applied for haskap juice extraction. Both physicochemical assays and tests of antioxidant activities were employed to evaluate the qualities of the haskap juice. Generally, the centrifugal juicer increased and the steam juicer reduced concentrations of measured juice components relative to the press. The juice from the centrifugal juicer had the highest cloudiness. Sugar concentrations were about 40% lower in steam juice compared to the centrifugal juicer. Pressed juice had a slightly lower soluble solid content than the juice made with the centrifugal juicer and concentrations of glucose and fructose were similar between these methods. The methods altered pH and malic acid content without affecting the concentrations of tartaric and malic acids. Similar effects of juicing methods were seen in secondary compounds associated with health benefits and antioxidant capacities. Anthocyanin concentrations in press and centrifugal juicer extracts were similar, about 1.6 times higher than steam juicer extracts. Total phenolics and antioxidant activities were from two to four times higher in the centrifugal juicer extraction compared to steam juicing. Ascorbic acid and total flavonoid content in the haskap juice was increased by centrifugal juicing and decreased by steam juicing compared to the press. Overall, the juice extracted with the centrifugal juicer had concentrations of juice components that were 1.5–2 times higher than the steam juicer. The pressed juice had similar to slightly lower concentrations of components compared to the centrifugal juicer.
Application of Machine Learning to Assess the Quality of Food Products—Case Study: Coffee Bean
Authors: Przybył Krzysztof , Gawrysiak-Witulska Marzena , Bielska Paulina , Rusinek Robert , Gancarz Marek , Dobrzański Bohdan , Siger Aleksander
Published: September 2023

Modern machine learning methods were used to automate and improve the determination of an effective quality index for coffee beans. Machine learning algorithms can effectively recognize various anomalies, among others factors, occurring in a food product. The procedure for preparing the machine learning algorithm depends on the correct preparation and preprocessing of the learning set. The set contained coded information (i.e., selected quality coefficients) based on digital photos (input data) and a specific class of coffee bean (output data). Because of training and data tuning, an adequate convolutional neural network (CNN) was obtained, which was characterized by a high recognition rate of these coffee beans at the level of 0.81 for the test set. Statistical analysis was performed on the color data in the RGB color space model, which made it possible to accurately distinguish three distinct categories of coffee beans. However, using the Lab* color model, it became apparent that distinguishing between the quality categories of under-roasted and properly roasted coffee beans was a major challenge. Nevertheless, the Lab* model successfully distinguished the category of over-roasted coffee beans.
A Novel and Optimized Sine–Cosine Transform Wavelet Threshold Denoising Method Based on the sym4 Basis Function and Adaptive Threshold Related to Noise Intensity
Authors: Guo Yinhui , Zhou Xinda , Li Jie , Ba Rongsheng , Xu Zhaorui , Tu Shuai , Chai Liqun
Published: September 2023

In digital shearography, the speckle noise of the phase fringe pattern has a negative effect on the accuracy and reliability of the phase unwrapping procedure. A novel and optimized sine–cosine transform wavelet threshold denoising method is proposed to suppress speckle noise. Fast phase denoising can be achieved by using the proposed method while preserving the phase reversal information. The details of the selected wavelet basis function, the optimal decomposition level, the threshold function, and the denoising threshold are also provided in this manuscript. In particular, the decomposition level is analyzed and optimized through simulation analysis according to the speckle suppression index and the adaptive denoising method. The experimental results show that the proposed method has more adaptive ability in practical application than the sine–cosine transform average denoising method with the selected mask and iterative procedure, which speeds the denoising process up and takes better-unwrapped phase patterns.
Space and Time
Authors: Nute Kevin
Published: September 2023

In 1972, the urban designer Kevin Lynch concluded the book What Time Is This Place [...]
Analysis of Hotspots and Trends in Soil Moisture Research since the 21st Century
Authors: Cai Yuanxiang , Yang Yaping , Yue Xiafang , Xu Yang
Published: September 2023

Soil moisture is a key factor in ecosystems that profoundly affects carbon, nitrogen, and water cycles on land surfaces, vegetation growth, and climate change. Consequently, numerous scholars have researched and authored scientific literature on soil moisture and related topics. Using the Web of Science database, we conducted a bibliometric analysis of 60,581 papers published in the field of soil moisture between 2000 and 2022. The findings revealed the following trends. (1) The number of publications on soil moisture has consistently increased in the 21st century at an increasing rate. For instance, although the annual increase was only 94 publications in 2005, it surged to 321 publications in 2020. (2) The United States (US), China, and developed European countries emerged as primary research institutions and authors. The US occupies a leading position in soil moisture research, boasting the highest number of publications and total citations in the field, whereas China ranks second in both publications and total citations. (3) Regarding international collaboration, the US has established close partnerships with numerous international research institutions. However, China’s international cooperation in this field requires improvement. (4) The Journal of Hydrology holds the top position in terms of both the total number of published articles and citations. Research on water resources ranked first in terms of its H-index. (5) Keyword analysis highlighted several current research hotspots, including the coupled covariance effect of soil moisture and land surface environmental factors in the context of climate change, soil moisture utilization rate, crop yield, influence mechanism of soil moisture on soil ecosystem structure, and development of high-precision soil moisture data products. In conclusion, this study provides a systematic review of the research hotspots and trends in soil moisture studies in the 21st century. The objective is to offer a comprehensive reference to aid in understanding the evolutionary patterns of soil moisture research in multiple dimensions.
Atmospheric Transport of Adulticides Used to Control Mosquito Populations across an Urban Metropolitan Area
Authors: Guberman VerPloeg Sarah L. , Yoon Subin , Alvarez Sergio L. , Flynn James H. , Collins Don , Griffin Robert J. , Sheesley Rebecca J. , Usenko Sascha
Published: September 2023

Pesticides registered with the U.S. EPA for mosquito control are called adulticides and are released directly into the atmosphere as aerosols to target flying mosquitos. This adulticide application approach is different from traditional (agricultural) pesticide applications, yet the fate and transport of adulticides in large metropolitan areas is largely unknown. The Houston Metropolitan Area encompasses eight counties, many of which require county-level mosquito control programs that utilize adulticides. Malathion and permethrin are the primary adulticides used by Harris County (HC) in Houston, TX, USA. Houston, like many other metropolitan areas, has an urban atmosphere supporting the oxidation of both gas and particle phase pollutants. During the summer mosquito season of 2016, we collected atmospheric total suspended particulate matter (PM) samples at Jones Forest (JF), located in Montgomery County (directly north of HC) to investigate the atmospheric transport and oxidation of adulticides in an urban atmosphere. Despite HC alternating the adulticide treatment schedule, we measured permethrin, malathion, and malaoxon (oxidation product of malathion), throughout the sampling campaign. These consistent measurements, in conjunction with 12 h backward trajectories, support the conclusion that JF is influenced by other county-level mosquito-control programs and agricultural pesticide use. This cross-county transport may impact adulticide effectiveness by supporting pesticide resistance in mosquito populations due to repeated exposures to pesticides. This study highlights the need for mosquito control collaborations between counties, especially in areas of urban expansion overlapping with agricultural activities.
Assessment of NEX-GDDP-CMIP6 Downscale Data in Simulating Extreme Precipitation over the Huai River Basin
Authors: Jiang Fushuang , Wen Shanshan , Gao Miaoni , Zhu Aiping
Published: September 2023

This study aimed to assess the performance of 35 global climate models included in NEX-GDDP-CMIP6, derived from downscaling CMIP6 data to high spatial (25 km) and temporal (daily) resolutions, in reproducing extreme precipitation events over the Huai River Basin. Eight widely used extreme precipitation indices were employed to quantitatively describe the models’ capability of simulation. Results indicate that the majority of models can reasonably capture trends, with UKESM1-0-LL performing the best among all considered models. All models demonstrate high accuracy in simulating climatological means, especially for the total precipitation (PRCPTOT), displaying a spatial correlation coefficient exceeding 0.8 when compared to the observed data. NorESM2-MM and MRI-ESM2-0 can accurately simulate the frequency and intensity of extreme precipitation, respectively. In general, UKESM1-0-LL, CESM2, MIROC6, MRI-ESM2-0, CMCC-CM2-SR5, and MPI-ESM-2-LR exhibit superior simulation capabilities in terms of capturing both the trends and climatology of extreme precipitation. The aforementioned findings provide guidance for future studies on the regional impacts of climate change using NEX model data, and therefore hold great importance in comprehending the regional impacts of, and the adaptability to, climate change, as well as the development of adaptation strategies.
Mortality during Heatwaves and Tropical Nights in Vienna between 1998 and 2022
Authors: Hagen Manuel , Weihs Philipp
Published: September 2023

Rising summer temperatures lead to heat waves and tropical nights, which can result in health problems among the population. This work examined if mortality among Viennese people has increased under such weather conditions or whether the population was able to adapt to those periods of extreme heat. Therefore, the daily climatic data of the Austrian Weather Service and the number of daily deaths in Vienna from 1998 to 2022 have been put into relation. After calculating the mean values from those data sets, we analyzed the total number of daily deaths but also the death rate per 100,000 inhabitants for the total Viennese population, for men and women. The impact of age structure on possible trends was analyzed and ruled out. The analysis showed that the mortality on days with heat events was still higher, but the mean values of daily deaths decreased over time, despite a doubling of heatwaves and tropical nights, which speaks for an adaptation to heat events by the Viennese population.
Impact of Anthropogenic Heat on Urban Environment: A Case Study of Singapore with High-Resolution Gridded Data
Authors: Wang Ao , Li Xian-Xiang , Xin Rui , Chew Lup Wai
Published: September 2023

Anthropogenic heat (AH) emissions have great impacts on urban climate. AH is usually spatially heterogeneous and depends on the urban land use type. Studies using high-resolution gridded data that can resolve spatially heterogeneous AH are still scarce. The present study uses AH data of a high spatial resolution of 200 m by 200 m and a temporal resolution of 1 h to investigate the impact of AH in Singapore in April 2016, particularly regarding the relative contribution of individual AH components. The WRF model coupled with a single-layer urban canopy model is employed. The WRF model can predict the 2-m air temperature and 2-m relative humidity with good agreement with the observation data, while the simulated 10-m wind speed has relatively large deviation from the observation data. The largest spatially averaged temperature increases caused by total AH (QF), AH from buildings (QB) and AH from traffic (QV) are 1.44 °C, 1.44 °C and 1.35 °C, respectively. The effects of AH on sensible heat flux and boundary layer height are largely consistent, with both QF and QB exhibiting significant effects at night, while the effects of QV are small. The effect of AH on the local circulations (sea and land breezes) in Singapore is small, while its effect on the urban heat island (UHI) circulations is more pronounced. Due to the UHI circulations, the sum of the effects on local temperatures caused by QB and QV may exceed that by QF in some areas. This finding can guide comprehensive mitigation measures of AH by not only focusing on land use type but also on the contribution of individual AH components, in order to ameliorate the impacts of urban overheating.
Bayesian Estimation Using Product of Spacing for Modified Kies Exponential Progressively Censored Data
Authors: Kurdi Talal , Nassar Mazen , Alam Farouq Mohammad A.
Published: September 2023

In life testing and reliability studies, most researchers have used the maximum likelihood estimation method to estimate unknown parameters, even though it has been proven that the maximum product of spacing method has properties as good as the maximum likelihood estimation method and sometimes even better. In this study, we aim to estimate the unknown parameters of the modified Kies exponential distribution along with the reliability and hazard rate functions under progressive type-II censoring scheme. The maximum likelihood and maximum product of spacing methods are considered in order to find the point estimates and approximate confidence intervals of the various parameters. Moreover, Bayesian estimations based on the likelihood function and the product of the spacing function of the unknown parameters are obtained using the squared error loss function with independent gamma priors. It is observed that the joint posterior distributions have complicated forms. Because of this, Lindley’s approximation and the Markov chain Monte Carlo technique are used to obtain the Bayesian estimates and highest posterior credible intervals. Monte Carlo simulations are performed in order to evaluate the performance of the proposed estimation methods. Two real datasets are studied to demonstrate the efficacy of the offered methodologies and highlight how simple and applicable it might be to apply them in practical fields.
ω-Limit Sets of Impulsive Semigroups for Hyperbolic Equations
Authors: Feketa Petro , Fedorenko Juliya , Bezushchak Dmytro , Sukretna Anna
Published: September 2023

In this paper, we investigate the qualitative behavior of an evolutionary problem consisting of a hyperbolic dissipative equation whose trajectories undergo instantaneous impulsive discontinuities at the moments when the energy functional reaches a certain threshold value. The novelty of the current study is that we consider the case in which the entire infinite-dimensional phase vector undergoes an impulsive disturbance. This substantially broadens the existing results, which admit discontinuities for only a finite subset of phase coordinates. Under fairly general conditions on the system parameters, we prove that such a problem generates an impulsive dynamical system in the natural phase space, and its trajectories have nonempty compact ω-limit sets.
Research on Price Discrimination Behavior Governance of E-Commerce Platforms—A Bayesian Game Model Based on the Right to Data Portability
Authors: Yu Jing , Jia Wensheng
Published: September 2023

The behavior of e-commerce platforms using big data algorithms to implement “big data killing” is not only rejected by regular customers, but also creates many difficulties for supervision by relevant government departments. In order to study how to curb the price discrimination behavior of e-commerce platforms in the case of taking regular customers as the leaders, this paper introduces the right to data portability and considers two types of regular customers with high price sensitivity and low price sensitivity. Then, we build a Bayesian game model between e-commerce platforms and regular customers on the basis of the established general game model. Our experiments show that when the reuse value coefficient of personal data is high, the e-commerce platform will choose a uniform pricing strategy, which indicates that the right to data portability can curb the price discrimination behavior of the e-commerce platform to a certain extent. Moreover, when the proportion of high-sensitivity consumers among regular customers increases, e-commerce platforms will be prompted to choose the uniform pricing strategy, which indicates that consumers can curb price discrimination behaviour on e-commerce platforms by increasing their sensitivity for price change.
2-D Elastodynamic Time-Reversal Analysis for Surface Defects on Thin Plate Using Topological Sensitivity
Authors: Saitoh Takahiro
Published: September 2023

In recent years, there has been increasing attention on the development of non-destructive evaluation (NDE) methods using guided waves for long-length materials such as thin plates and pipes. The guided waves are capable of long-distance propagation in thin plates and pipes, and they exhibit properties such as multimodality and dispersion. These characteristics of the guided waves make inspection using guided waves challenging. In this study, we apply a 2-D elastodynamic time-reversal method to detect surface breaking cracks of a thin plate where guided waves are present. The finite element method (FEM) is used to calculate the scattered waves from surface breaking cracks and their corresponding time-reversal waves. We also employ topological sensitivity as an assessment index for detecting surface breaking cracks using the time-reversal method. As numerical examples, we demonstrate guided wave propagation, scattering, and the time-reversal wave propagation obtained by using the FEM. Finally, we present the results of surface breaking crack detection in a thin plate and discuss the validity and effectiveness of the proposed method.
Development of an Intuitive GUI-Based Fuzzy Multi-Criteria Decision Model for Comprehensive Hospital Service Quality Evaluation and Indexing
Authors: Rehman Ateekh Ur , Abidi Mustufa Haider , Usmani Yusuf Siraj , Mian Syed Hammad , Alkhalefah Hisham
Published: September 2023

Recently, hospital care and other services have become increasingly important for patient satisfaction. Better hospital care and assistance improve patients’ medical conditions, management trust, and financial success. In this regard, monitoring and measuring hospital service quality is necessary to improve patient satisfaction and wellness. However, the evaluation of healthcare service quality is a complex and critical task due to its intangible nature. Existing methodologies often struggle to effectively incorporate multiple criteria and address uncertainties inherent in healthcare evaluations. To address these challenges, this research work seeks to develop a comprehensive and robust approach for evaluating hospital service quality to improve decision making and resource allocation for service enhancement. This study aims to evaluate multi-faceted healthcare service quality by combining many criteria and uncertainties into a single index. The model is constructed methodically utilizing fuzzy logic and decision modeling. A dataset collected from diverse healthcare facilities covering various medical specialties and regions is employed to validate and refine the model. Numerous criteria, factors, and dimensions are examined and embedded into the development of the model. Fuzzy logic is used to capture and manage healthcare evaluations’ inherent vagueness and imprecision, yielding more accurate and comprehensive outcomes. The model’s outcome is the hospital service quality fuzzy index (HSQFI), an easy-to-understand single performance measure. A graphical user interface (GUI) is developed for collecting data, and then it shows the results in the form of barriers and recommendations. Based on the findings, recommendations in terms of barriers (service criteria) to enhance the hospital’s service quality have been made. This approach can be a tool for managers or other stakeholders to quickly realize the success of their service plans and pinpoint areas that may need improvement in the future.
Mathematical Model of Cyber Risks Management Based on the Expansion of Piecewise Continuous Analytical Approximation Functions of Cyber Attacks in the Fourier Series
Authors: Sobchuk Valentyn , Barabash Oleg , Musienko Andrii , Tsyganivska Iryna , Kurylko Oleksandr
Published: September 2023

The comprehensive system of information security of an enterprise includes both tactical aspects of information and strategic priorities, reflecting the information policy and information strategy of the enterprise. Ensuring a given level of cybersecurity requires the identification of threat actors, their purpose, intentions of attacks on the IT infrastructure, and weak points of the enterprise’s information security. To achieve these goals, enterprises need new information security solutions. In this work, a mathematical model of the process of cyber risk management in the enterprise, which is based on the distribution of piecewise continuous analytical approximating functions of cyber attacks in the Fourier series, is obtained. A constant continuous monitoring and conduction of cyber regulatory control of the enterprise on time makes it possible to effectively ensure the cybersecurity of the enterprise in real time—predicting the emergence of cyber threats to some extent—which, in turn, determines the management of cyber risks arising in the field of information security of the enterprise. Such a Fourier series expansion of the piecewise continuous analytical approximating function of the intensity of cyber attacks on damage to standard software, obtained by approximating empirical–statistical slices of the intensity of cyber attacks on damage to standard software for each time period by analytical functions, opens up new mathematical possibilities of transition to systems of regulatory control of cyber threats of the enterprise from discrete to continuous automated process for such types of control.
The Probabilistic Dual Hesitant Fuzzy Multi-Attribute Decision-Making Method Based on Cumulative Prospect Theory and Its Application
Authors: Zhang Wenyu , Zhu Yuting
Published: September 2023

Addressing the complex issue of multi-attribute decision-making within a probabilistic dual hesitant fuzzy context, where attribute weights are unknown, a novel decision-making method based on cumulative prospect theory is proposed, named the probabilistic dual hesitant fuzzy multi-attribute decision-making method based on cumulative prospect theory. Firstly, a decision matrix is formulated, representing probabilistic dual hesitant fuzzy information. Secondly, according to the decision maker’s authentic preference and non-membership information sensitivity, a comprehensive score function suitable for probabilistic dual hesitant fuzzy elements is proposed. The attribute weights are then determined using the entropy method. Next, the value function and decision weight function from the cumulative prospect theory are employed to compute the cumulative prospect value attributed to each available scheme. In addition, a cumulative prospect matrix is constructed, enabling the establishment of scheme rankings based on the comprehensive cumulative prospect value. Finally, the analysis of specific cases and a comparative assessment of methods pertaining to the selection of emergency response schemes collectively demonstrate the rationality and efficacy of the decision-making method presented in this study.
Extension of Fuzzy ELECTRE I for Evaluating Demand Forecasting Methods in Sustainable Manufacturing
Authors: Chu Ta-Chung , Nghiem Thi Bich Ha
Published: September 2023

The selection of a demand forecasting method is critical for companies aiming to avoid manufacturing overproduction or shortages in pursuit of sustainable development. Various qualitative and quantitative criteria with different weights must be considered during the evaluation of a forecasting method. The qualitative criteria and criteria weights are usually assessed in linguistic terms. Aggregating these various criteria and linguistic weights for evaluating and selecting demand forecasting methods in sustainable manufacturing is a major challenge. This paper proposes an extension of fuzzy elimination and choice translating reality (ELECTRE) I to resolve this problem. In the proposed method, fuzzy weighted ratings are defuzzified with the signed distance to develop a crisp ELECTRE I model. Moreover, an extension to ELECTRE I is developed by suggesting an extended modified discordance matrix and a closeness coefficient for ranking alternatives. The proposed extension can overcome the problem of information loss, which can lead to incorrect ranking results when using the Hadamard product to combine concordance and modified discordance matrices. A comparison is conducted to show the advantage of the proposed extension. Finally, a numerical example is used to demonstrate the feasibility of the proposed method. Furthermore, a numerical comparison is made to display the advantage of the proposed method.
AIMS: An Automatic Semantic Machine Learning Microservice Framework to Support Biomedical and Bioengineering Research
Authors: Yu Hong Qing , O’Neill Sam , Kermanizadeh Ali
Published: September 2023

The fusion of machine learning and biomedical research offers novel ways to understand, diagnose, and treat various health conditions. However, the complexities of biomedical data, coupled with the intricate process of developing and deploying machine learning solutions, often pose significant challenges to researchers in these fields. Our pivotal achievement in this research is the introduction of the Automatic Semantic Machine Learning Microservice (AIMS) framework. AIMS addresses these challenges by automating various stages of the machine learning pipeline, with a particular emphasis on the ontology of machine learning services tailored to the biomedical domain. This ontology encompasses everything from task representation, service modeling, and knowledge acquisition to knowledge reasoning and the establishment of a self-supervised learning policy. Our framework has been crafted to prioritize model interpretability, integrate domain knowledge effortlessly, and handle biomedical data with efficiency. Additionally, AIMS boasts a distinctive feature: it leverages self-supervised knowledge learning through reinforcement learning techniques, paired with an ontology-based policy recording schema. This enables it to autonomously generate, fine-tune, and continually adapt to machine learning models, especially when faced with new tasks and data. Our work has two standout contributions demonstrating that machine learning processes in the biomedical domain can be automated, while integrating a rich domain knowledge base and providing a way for machines to have self-learning ability, ensuring they handle new tasks effectively. To showcase AIMS in action, we have highlighted its prowess in three case studies of biomedical tasks. These examples emphasize how our framework can simplify research routines, uplift the caliber of scientific exploration, and set the stage for notable advances.
Individual Immune Response to SARS-CoV-2 Infection—The Role of Seasonal Coronaviruses and Human Leukocyte Antigen
Authors: Rottmayer Karla , Loeffler-Wirth Henry , Gruenewald Thomas , Doxiadis Ilias , Lehmann Claudia
Published: September 2023

During the coronavirus pandemic, evidence is growing that the severity, susceptibility and host immune response to SARS-CoV-2 infection can be highly variable. Several influencing factors have been discussed. Here, we investigated the humoral immune response against SARS-CoV-2 spike, S1, S2, the RBD, nucleocapsid moieties and S1 of seasonal coronaviruses: hCoV-229E, hCoV-HKU1, hCoV-NL63 and hCoV-OC43, as well as MERS-CoV and SARS-CoV, in a cohort of 512 individuals. A bead-based multiplex assay allowed simultaneous testing for all the above antigens and the identification of different antibody patterns. Then, we correlated these patterns with 11 HLA loci. Regarding the seasonal coronaviruses, we found a moderate negative correlation between antibody levels against hCoV-229E, hCoV-HKU1 and hCoV-NL63 and the SARS-CoV-2 antigens. This could be an indication of the original immunological imprinting. High and low antibody response patterns were distinguishable, demonstrating the individuality of the humoral response towards the virus. An immunogenetical factor associated with a high antibody response (formation of ≥4 different antibodies) was the presence of HLA A*26:01, C*02:02 and DPB1*04:01 alleles, whereas the HLA alleles DRB3*01:01, DPB1*03:01 and DB1*10:01 were enriched in low responders. A better understanding of this variable immune response could enable more individualized protective measures.
New Insights on Sperm Function in Male Infertility of Unknown Origin: A Multimodal Approach
Authors: Pacheco Rita I. , Cristo Maria I. , Anjo Sandra I. , Silva Andreia F. , Sousa Maria Inês , Tavares Renata S. , Sousa Ana Paula , Almeida Santos Teresa , Moura-Ramos Mariana , Caramelo Francisco , Manadas Bruno , Ramalho-Santos João , Amaral Sandra Gomes
Published: September 2023

The global trend of rising (male) infertility is concerning, and the unidentifiable causes in half of the cases, the so-called unknown origin male infertility (UOMI), demands a better understanding and assessment of both external/internal factors and mechanisms potentially involved. In this work, it was our aim to obtain new insight on UOMI, specifically on idiopathic (ID) and Unexplained male infertility (UMI), relying on a detailed evaluation of the male gamete, including functional, metabolic and proteomic aspects. For this purpose, 1114 semen samples, from males in couples seeking infertility treatment, were collected at the Reproductive Medicine Unit from the Centro Hospitalar e Universitário de Coimbra (CHUC), from July 2018–July 2022. Based on the couples’ clinical data, seminal/hormonal analysis, and strict eligibility criteria, samples were categorized in 3 groups, control (CTRL), ID and UMI. Lifestyle factors and anxiety/depression symptoms were assessed via survey. Sperm samples were evaluated functionally, mitochondrially and using proteomics. The results of Assisted Reproduction Techniques were assessed whenever available. According to our results, ID patients presented the worst sperm functional profile, while UMI patients were similar to controls. The proteomic analysis revealed 145 differentially expressed proteins, 8 of which were specifically altered in ID and UMI samples. Acrosin (ACRO) and sperm acrosome membrane-associated protein 4 (SACA4) were downregulated in ID patients while laminin subunit beta-2 (LAMB2), mannose 6-phosphate isomerase (MPI), ATP-dependent 6-phosphofructokinase liver type (PFKAL), STAR domain-containing protein 10 (STA10), serotransferrin (TRFE) and exportin-2 (XPO2) were downregulated in UMI patients. Using random forest analysis, SACA4 and LAMB2 were identified as the sperm proteins with a higher chance of distinguishing ID and UMI patients, and their function and expression variation were in accordance with the functional results. No alterations were observed in terms of lifestyle and psychological factors among the 3 groups. These findings obtained in an experimental setting based on 3 well-defined groups of subjects, might help to validate new biomarkers for unknown origin male infertility (ID and UMI) that, in the future, can be used to improve diagnostics and treatments.
Regulation of Syntaxin3B-Mediated Membrane Fusion by T14, Munc18, and Complexin
Authors: Nishad Rajkishor , Betancourt-Solis Miguel , Dey Himani , Heidelberger Ruth , McNew James A.
Published: September 2023

Retinal neurons that form ribbon-style synapses operate over a wide dynamic range, continuously relaying visual information to their downstream targets. The remarkable signaling abilities of these neurons are supported by specialized presynaptic machinery, one component of which is syntaxin3B. Syntaxin3B is an essential t-SNARE protein of photoreceptors and bipolar cells that is required for neurotransmitter release. It has a light-regulated phosphorylation site in its N-terminal domain at T14 that has been proposed to modulate membrane fusion. However, a direct test of the latter has been lacking. Using a well-controlled in vitro fusion assay, we found that a phosphomimetic T14 syntaxin3B mutation leads to a small but significant enhancement of SNARE-mediated membrane fusion following the formation of the t-SNARE complex. While the addition of Munc18a had only a minimal effect on membrane fusion mediated by SNARE complexes containing wild-type syntaxin3B, a more significant enhancement was observed in the presence of Munc18a when the SNARE complexes contained a syntaxin3B T14 phosphomimetic mutant. Finally, we showed that the retinal-specific complexins (Cpx III and Cpx IV) inhibited membrane fusion mediated by syntaxin3B-containing SNARE complexes in a dose-dependent manner. Collectively, our results establish that membrane fusion mediated by syntaxin3B-containing SNARE complexes is regulated by the T14 residue of syntaxin3B, Munc18a, and Cpxs III and IV.
Harnessing Oleanolic Acid and Its Derivatives as Modulators of Metabolic Nuclear Receptors
Authors: Radwan Mohamed O. , Kadasah Sultan F. , Aljubiri Salha M. , Alrefaei Abdulmajeed F. , El-Maghrabey Mahmoud H. , El Hamd Mohamed A. , Tateishi Hiroshi , Otsuka Masami , Fujita Mikako
Published: September 2023

Nuclear receptors (NRs) constitute a superfamily of ligand-activated transcription factors with a paramount role in ubiquitous physiological functions such as metabolism, growth, and reproduction. Owing to their physiological role and druggability, NRs are deemed attractive and valid targets for medicinal chemists. Pentacyclic triterpenes (PTs) represent one of the most important phytochemical classes present in higher plants, where oleanolic acid (OA) is the most studied PTs representative owing to its multitude of biological activities against cancer, inflammation, diabetes, and liver injury. PTs possess a lipophilic skeleton that imitates the NRs endogenous ligands. Herein, we report a literature overview on the modulation of metabolic NRs by OA and its semi-synthetic derivatives, highlighting their health benefits and potential therapeutic applications. Indeed, OA exhibited varying pharmacological effects on FXR, PPAR, LXR, RXR, PXR, and ROR in a tissue-specific manner. Owing to these NRs modulation, OA showed prominent hepatoprotective properties comparable to ursodeoxycholic acid (UDCA) in a bile duct ligation mice model and antiatherosclerosis effect as simvastatin in a model of New Zealand white (NZW) rabbits. It also demonstrated a great promise in alleviating non-alcoholic steatohepatitis (NASH) and liver fibrosis, attenuated alpha-naphthol isothiocyanate (ANIT)-induced cholestatic liver injury, and controlled blood glucose levels, making it a key player in the therapy of metabolic diseases. We also compiled OA semi-synthetic derivatives and explored their synthetic pathways and pharmacological effects on NRs, showcasing their structure-activity relationship (SAR). To the best of our knowledge, this is the first review article to highlight OA activity in terms of NRs modulation.
Cannabidiol Modulates M-Type K+ and Hyperpolarization-Activated Cation Currents
Authors: Liu Yen-Chin , So Edmund Cheung , Wu Sheng-Nan
Published: September 2023

Cannabidiol (CBD) is a naturally occurring compound found in the Cannabis plant that is known for its potential therapeutic effects. However, its impact on membrane ionic currents remains a topic of debate. This study aimed to investigate how CBD modifies various types of ionic currents in pituitary GH3 cells. Results showed that exposure to CBD led to a concentration-dependent decrease in M-type K+ currents (IK(M)), with an IC50 of 3.6 μM, and caused the quasi-steady-state activation curve of the current to shift to a more depolarized potential with no changes in the curve’s steepness. The CBD-mediated block of IK(M) was not reversed by naloxone, suggesting that it was not mediated by opioid receptors. The IK(M) elicited by pulse-train stimulation was also decreased upon exposure to CBD. The magnitude of erg-mediated K+ currents was slightly reduced by adding CBD (10 μM), while the density of voltage-gated Na+ currents elicited by a short depolarizing pulse was not affected by it. Additionally, CBD decreased the magnitude of hyperpolarization-activated cation currents (Ih) with an IC50 of 3.3 μM, and the decrease was reversed by oxaliplatin. The quasi-steady-state activation curve of Ih was shifted in the leftward direction with no changes in the slope factor of the curve. CBD also diminished the strength of voltage-dependent hysteresis on Ih elicited by upright isosceles-triangular ramp voltage. Collectively, these findings suggest that CBD’s modification of ionic currents presented herein is independent of cannabinoid or opioid receptors and may exert a significant impact on the functional activities of excitable cells occurring in vitro or in vivo.
Preventive Action of Beta-Carotene against the Indoxyl Sulfate-Induced Renal Dysfunction in Male Adult Zebrafish via Regulations of Mitochondrial Inflammatory and β-Carotene Oxygenase-2 Actions
Authors: Muthuraman Arunachalam , Sayem Abu Sadat Md. , Meenakshisundaram Sakthiganapathi , Ali Nemat , Ahmad Sheikh F. , AlAsmari Abdullah F. , Nishat Shamama , Lim Khian Giap , Paramaswaran Yamunna
Published: September 2023

Indoxyl sulfate (IS) is a metabolic byproduct of indole metabolism. IS readily interacts with the mitochondrial redox metabolism, leading to altered renal function. The β-carotene oxygenase-2 (BCO2) enzyme converts carotenoids to intermediate products. However, the role of β-carotene (BC) in IS-induced renal dysfunction in zebrafish and their modulatory action on BCO2 and mitochondrial inflammations have not been explored yet. Hence, the present study is designed to investigate the role of BC in the attenuation of IS-induced renal dysfunction via regulations of mitochondrial redox balance by BCO2 actions. Renal dysfunction was induced by exposure to IS (10 mg/L/hour/day) for 4 weeks. BC (50 and 100 mg/L/hour/day) and coenzyme Q10 (CoQ10; 20 mg/L/hour/day) were added before IS exposure. BC attenuated the IS-induced increase in blood urea nitrogen (BUN) and creatinine concentrations, adenosine triphosphate (ATP), and complex I activity levels, and the reduction of renal mitochondrial biomarkers, i.e., BCO2, superoxide dismutase-2 (SOD2), glutathione peroxidase-1 (GPX1), reduced and oxidized glutathione (GSH/GSSG) ratio, and carbonylated proteins. Moreover, renal histopathological changes were analyzed by the eosin and hematoxylin staining method. As a result, the administration of BC attenuated the IS-induced renal damage via the regulation of mitochondrial function.
Combined Presence in Heterozygosis of Two Variant Usher Syndrome Genes in Two Siblings Affected by Isolated Profound Age-Related Hearing Loss
Authors: Borgese Nica , Guillén-Samander Andrés , Colombo Sara Francesca , Mancassola Giulia , Di Berardino Federica , Zanetti Diego , Carrera Paola
Published: September 2023

Sensorineural age-related hearing loss affects a large proportion of the elderly population, and has both environmental and genetic causes. Notwithstanding increasing interest in this debilitating condition, the genetic risk factors remain largely unknown. Here, we report the case of two sisters affected by isolated profound sensorineural hearing loss after the age of seventy. Genomic DNA sequencing revealed that the siblings shared two monoallelic variants in two genes linked to Usher Syndrome (USH genes), a recessive disorder of the ear and the retina: a rare pathogenic truncating variant in USH1G and a previously unreported missense variant in ADGRV1. Structure predictions suggest a negative effect on protein stability of the latter variant, allowing its classification as likely pathogenic according to American College of Medical Genetics criteria. Thus, the presence in heterozygosis of two recessive alleles, which each cause syndromic deafness, may underlie digenic inheritance of the age-related non-syndromic hearing loss of the siblings, a hypothesis that is strengthened by the knowledge that the two genes are integrated in the same functional network, which underlies stereocilium development and organization. These results enlarge the spectrum and complexity of the phenotypic consequences of USH gene mutations beyond the simple Mendelian inheritance of classical Usher syndrome.
From-Toilet-to-Freezer: A Review on Requirements for an Automatic Protocol to Collect and Store Human Fecal Samples for Research Purposes
Authors: Widjaja Frances , Rietjens Ivonne M. C. M.
Published: September 2023

The composition, viability and metabolic functionality of intestinal microbiota play an important role in human health and disease. Studies on intestinal microbiota are often based on fecal samples, because these can be sampled in a non-invasive way, although procedures for sampling, processing and storage vary. This review presents factors to consider when developing an automated protocol for sampling, processing and storing fecal samples: donor inclusion criteria, urine–feces separation in smart toilets, homogenization, aliquoting, usage or type of buffer to dissolve and store fecal material, temperature and time for processing and storage and quality control. The lack of standardization and low-throughput of state-of-the-art fecal collection procedures promote a more automated protocol. Based on this review, an automated protocol is proposed. Fecal samples should be collected and immediately processed under anaerobic conditions at either room temperature (RT) for a maximum of 4 h or at 4 °C for no more than 24 h. Upon homogenization, preferably in the absence of added solvent to allow addition of a buffer of choice at a later stage, aliquots obtained should be stored at either −20 °C for up to a few months or −80 °C for a longer period—up to 2 years. Protocols for quality control should characterize microbial composition and viability as well as metabolic functionality.
Advances in Folic Acid Biosensors and Their Significance in Maternal, Perinatal, and Paediatric Preventive Medicine
Authors: Movendane Yogesh , Sipalo Mbozu G. , Chan Leon C. Z.
Published: September 2023

Auxotrophic primates like human beings rely on exogenous dietary vitamin B9 supplementation to meet their metabolic demands. Folates play a crucial role in nucleotide synthesis and DNA methylation. Maternal folate deficiency causes several pregnancy-related complications, perinatal defects, and early childhood cognitive impairments. New evidence suggests excess FA is a potential risk factor resulting in unfavourable genomic and epigenomic alterations. Thus, it is essential to revisit the need to consistently monitor maternal folate levels during pregnancy. Yet, to date, no point-of-care folate-monitoring biosensor is commercially available. Here, we critically appraise the advances in folate biosensors to understand the translational gaps in biosensor design. Further, our review sheds light on the potential role of folate biosensors in strengthening maternal, perinatal, and child healthcare.
The Perfect Match! A Review and Tutorial on Issues Related to Matching Groups in Investigations of Children with Neurodevelopmental Conditions
Authors: Messer David , Henry Lucy A. , Danielsson Henrik
Published: September 2023

Research concerned with children and young people who have neurodevelopmental disabilities (ND) in relation to early language acquisition usually involves comparisons with matched group(s) of typically developing individuals. In these studies, several important and complex issues need to be addressed. Three major issues are related to: (1) the choice of a variables on which to carry out group matching; (2) recruiting children into the study; and (3) the statistical analysis of the data. To assist future research on this topic, we discuss each of these three issues and provide recommendations about what we believe to be the best course of action. To provide a comprehensive review of the methodological issues, we draw on research beyond the topic of early language acquisition. Our overall aim is to contribute to research that considers questions about delay or differences in development patterns of development and about identifying potentially causal variables.
Sexually Dimorphic Effects of Neuromodulatory Drugs on Normal and Stress-Induced Social Interaction in Rats
Authors: Ishaq Sara , Ahmed Touqeer
Published: September 2023

Social behavior is a complex term which involves different interactions between various individuals of a community. It is controlled by different neurotransmitter systems in a sexually dimorphic way. Certain environmental factors, like stress, cause various neurological disorders with associated social abnormalities in a sexually dimorphic way. Multiple drugs are used in clinical settings to treat behavioral disorders. However, the sexually dimorphic effects of these drugs, particularly on social behavior, still need to be studied. The present study was designed to investigate the sex-dependent effects of Risperidone, Donepezil, and Paroxetine in 8–12 weeks old male and female rats under normal and stressed conditions. There were four male and four female groups, i.e., control group (no drug treatment), Risperidone (3 mg/kg/day) treated group, Donepezil (5 mg/kg/day) treated group, and Paroxetine (10 mg/kg/day) treated group. Each group received its respective drug during phase 1 for 21 days, followed by a 10-day break with no drug treatment. After the break, same groups received the same drugs along with tilt-cage stress for an additional 21 days during phase 2. A social preference and novelty test was performed at the end of both phases (1 and 2). During phase 1, Risperidone treatment caused impaired social behavior and reduced locomotion in the male group only, compared to its control group. Donepezil treatment caused a reduction in social interaction, while Paroxetine treatment caused increased social interaction and locomotion in a sex-dependent manner. During phase 2, social novelty was affected in both male and female stress groups. Treatment with drugs along with stress showed differential sex-dependent effects. The study showed a predominant effect of Risperidone on males while there were differential effects of Donepezil and Paroxetine on both sexes. This study has paved the way for the development of more targeted and effective neuromodulatory drugs for use against various psychiatric and social deficits.