bluuebunny/crossref_metadata_2025 huggingface dataset:
Topic-Specific Pedagogical Content Knowledge-Based Instruction and Level of Conceptual Understanding of Chemical Kinetics and Equilibrium concepts on Grade 11 Students
Authors:   Department of Science and Mathematics Education, College of Education and Behavioral studies, Addis Ababa University, Addis Ababa, Ethiopia, Dejene Kassahun , Belachew Woldie ,   Department of Science and Mathematics Education, College of Education and Behavioral studies, Addis Ababa University, Addis Ababa, Ethiopia
Published: June 2023

The goal of this study was to assess students’ level of conceptual understanding of chemical kinetics and equilibrium using topic-specific pedagogical content knowledge (TSPCK)-based instruction in chemistry grade 11 students. The research was a mixed approach that involved 159 grade 11 chemistry class students from Addis Ababa administrative city, Ethiopia, and employed a mixture of qualitative and quantitative methodologies. Purposive sampling was used for the sample procedure and four intact classes were selected as three intervention groups and one control group: curricular saliency-based, representation-based, conceptual teaching strategy-based instruction, and comparison groups. The level of conceptual understanding was assessed using reasoned questions, specifically a two-tiered multiple-choice pretest, and posttest. The findings revealed that students’ conceptual understanding of chemical kinetics was higher than that of chemical equilibrium concepts. According to the findings of the students’ pretest and posttest, the level of conceptual understanding increased from 27.08% to 32.21% in chemical kinetics and from 15.91% to 23.68% in chemical equilibrium. Overall, representation-based instruction and conceptual teaching tactics boosted students’ conceptual knowledge and accomplishment in chemical kinetics and equilibrium concepts. This study proposes that the level of conceptual understanding of grade 11 students in chemical kinetics should take into account the horizontal relationship between mathematics and the chemical kinetics concepts, which should be taught using technology-assisted teaching strategies such as conceptual teaching strategies and three-fold mental representations.
A Study of Simulation-Role-Play Strategy on Pre-service Teachers’ Academic Performance in Basic Electronics
Authors:   Department of Science Education, Abetifi Presbyterian College of Education, Abetifi-Kwahu, Ghana,, Owiredu Joshua Kwabena , Asamoah Evans ,   Department of Science Education, Abetifi Presbyterian College of Education, Abetifi-Kwahu, Ghana,, Ankomah Richard ,   Department of Science Education, Abetifi Presbyterian College of Education, Abetifi-Kwahu, Ghana,, Aduamah Diana Amoabea ,   Gomoa Mampong Mpota Adawukwa Basic School, Central Region, Ghana
Published: June 2023

Achieving deeper and permanent learning has always been the focus of teaching force. This purpose is independent of the teaching level or subject matter. Pre-service teachers’ lack of interest and inability to connect learning levels are partly cited for their inability to develop this deeper and permanent learning of science concepts. In this respect, an action research design conducted using a case-study paradigm which included the simulation-role-play teaching strategy was used to teach pre-service teacher the concept of “doping of pure semiconductors” into p-type and n-type semiconductors. This is an area under basic electronics. The result of the non-parametric Wilcoxon Signed Rank Test analysis revealed a statistically significant increase in pre-service teachers’ performance level in basic electronics test following an intervention using the simulation-role-play approach. The median score of the performance level also increased from a pre-test score to post-test score. The simulation-role-play teaching approach affected student teachers’ learning of basic electronics by 55% which is considered a large effect. Further, when a sample of the pre-service teachers were interviewed, the result showed a positive view toward teaching using simulation approach which converts theoretical knowledge into practical knowledge for deeper understanding and permanent learning. The findings from this study would be helpful to student teachers and tutors in the colleges of education as it offered useful intervention in teaching and learning of doping of pure semiconductors.
Visualizing incompatibilities in phylogenetic trees using consensus outlines
Authors: Huson Daniel H. , Cetinkaya Banu
Published: June 2023

Phylogenetic analysis frequently leads to the creation of many phylogenetic trees, either from using multiple genes or methods, or through bootstrapping or Bayesian analysis. A consensus tree is often used to summarize what the trees have in common. Consensus networks were introduced to also allow the visualization of the main incompatibilities among the trees. However, in practice, such networks often contain a large number of nodes and edges, and can be non-planar, making them difficult to interpret. Here, we introduce the new concept of a phylogenetic consensus outline, which provides a planar visualization of incompatibilities in the input trees, without the complexities of a consensus network. Furthermore, we present an effective algorithm for its computation. We demonstrate its usage and explore how it compares to other methods on a Bayesian phylogenetic analysis of languages using data from a published database and on multiple gene trees from a published study on water lilies.
Finite element analysis of optimized novel additively manufactured non-articulating prostheses for cervical total disc replacement
Authors: Hsieh Ming-Kai , Tai Ching-Lung , Li Yun-Da , Lee De-Mei , Lin Cheng-Yi , Tsai Tsung-Ting , Lai Po-Liang , Chen Weng-Pin
Published: June 2023

Ball-and-socket designs of cervical total disc replacement (TDR) have been popular in recent years despite the disadvantages of polyethylene wear, heterotrophic ossification, increased facet contact force, and implant subsidence. In this study, a non-articulating, additively manufactured hybrid TDR with an ultra-high molecular weight polyethylene core and polycarbonate urethane (PCU) fiber jacket, was designed to mimic the motion of normal discs. A finite element (FE) study was conducted to optimize the lattice structure and assess the biomechanical performance of this new generation TDR with an intact disc and a commercial ball-and-socket Baguera®C TDR (Spineart SA, Geneva, Switzerland) on an intact C5-6 cervical spinal model. The lattice structure of the PCU fiber was constructed using the Tesseract or the Cross structures from the IntraLattice model in the Rhino software (McNeel North America, Seattle, WA) to create the hybrid I and hybrid II groups, respectively. The circumferential area of the PCU fiber was divided into three regions (anterior, lateral and posterior), and the cellular structures were adjusted. Optimal cellular distributions and structures were A2L5P2 in the hybrid I and A2L7P3 in the hybrid II groups. All but one of the maximum von Mises stresses were within the yield strength of the PCU material. The range of motions, facet joint stress, C6 vertebral superior endplate stress and path of instantaneous center of rotation of the hybrid I and II groups were closer to those of the intact group than those of the Baguera®C group under 100 N follower load and pure moment of 1.5 Nm in four different planar motions. Restoration of normal cervical spinal kinematics and prevention of implant subsidence could be observed from the FE analysis results. Superior stress distribution in the PCU fiber and core in the hybrid II group revealed that the Cross lattice structure of a PCU fiber jacket could be a choice for a next-generation TDR. This promising outcome suggests the feasibility of implanting an additively manufactured multi-material artificial disc that allows for better physiological motion than the current ball-and-socket design.
PLGA-based drug delivery systems in treating bone tumors
Authors: Qiu Enduo , Liu Fei
Published: June 2023

Bone tumor has become a common disease that endangers human health. Surgical resection of bone tumors not only causes biomechanical defects of bone but also destroys the continuity and integrity of bone and cannot completely remove the local tumor cells. The remaining tumor cells in the lesion bring a hidden danger of local recurrence. To improve the chemotherapeutic effect and effectively clear tumor cells, traditional systemic chemotherapy often requires higher doses, and high doses of chemotherapeutic drugs inevitably cause a series of systemic toxic side effects, often intolerable to patients. PLGA-based drug delivery systems, such as nano delivery systems and scaffold-based local delivery systems, can help eliminate tumors and promote bone regeneration and therefore have more significant potential for application in bone tumor treatment. In this review, we summarize the research progress of PLGA nano drug delivery systems and PLGA scaffold-based local delivery systems in bone tumor treatment applications, expecting to provide a theoretical basis for developing novel bone tumor treatment strategies.
Identifying the issues leading to residents’ modifications in Bahraini subsidized housing units
Authors: Lafi May Walid , Alkhalifa Haifa Ebrahim , Jiwane Anamika Vishal
Published: June 2023

Research problem and purpose: Residents’ modifications in subsidized housing are a widespread phenomenon in Bahrain. Households begin to modify their allocated residential units as soon as they receive them, resulting in financial burdens and an aesthetic loss of the uniform physical appearance. This research aims to identify the issues leading to residents’ modifications in Bahraini subsidized housing units.

Materials and methods: Literature indicates that this phenomenon is closely related to resident behaviors. Thus, the study presents a conceptual framework that examines the similarities and differences in residents’ behaviors in subsidized housing. Accordingly, the study employed the qualitative approach and was conducted in two phases. The first phase investigated common resident behaviors through structured interviews with twelve experts involved in the modification process. The second phase used the case study strategy with three selected cases from the East Hidd housing project to examine the different behaviors related to residents’ lifestyles. It included on-site observations, plan analysis, and structured interviews with householders using the AIO approach.

Results: The findings revealed general and specific issues that lead to residents' modifications. The general issues represent common behaviors for most residents and are usually associated with the prior-occupancy stage. They include residents’ preference for simple modern designs with spacious living rooms and bedrooms, trendy modern materials, and large windows; residents’ need for sustainable housing units that incorporate all three aspects of sustainability, particularly the socio-cultural, which is related to factors like privacy, hospitality, and the aesthetics and distinction of houses; and the damages resulting from the improper practices of residents that mainly revolve around excluding the experts and involving the unqualified in the modifications process. The specific issues represent families’ different behaviors and are usually associated with the post-occupancy stage. Those include residents’ need to modify their houses according to their lifestyles, which appeared in the guest room, the courtyard, and the interior divisions of the extended bedroom.

Conclusion: Considering both issues while designing future projects helps create flexible units that satisfy the needs of the majority while allowing for modifications at any time. This, in turn, helps reduce and streamline the modification process.
Chronic Inhibition of mROS Protects Against Coronary Endothelial Dysfunction in Mice With Diabetes
Authors: Xing Hang , Zhang Zhiqi , Shi Guangbin , He Yixin , Song Yi , Liu Yuhong , Harrington Elizabeth O. , Sellke Frank W. , Feng Jun
Published: June 2023

Graphical Abstract

Chronic hyperglycemia during diabetes causes persistent overproduction of mitochondrial ROS (mROS), resulting in inhibition of endothelial SK channel activity, impairment of coronary endothelium-dependent relaxation and dysregulation of antioxidant/pro-cell death enzyme. Chronic inhibition of mROS with mito-Tempo prevents endothelial mROS production resulting in increasing endothelial SK currents, enhancing antioxidant enzyme production, and improving coronary endothelium-dependent relaxation.
More than skin deep: cyclic peptides as wound healing and cytoprotective compounds
Authors: Lee Ying-Chiang J. , Javdan Bahar , Cowan Alexis , Smith Keith
Published: June 2023

The prevalence and cost of wounds pose a challenge to patients as well as the healthcare system. Wounds can involve multiple tissue types and, in some cases, become chronic and difficult to treat. Comorbidities may also decrease the rate of tissue regeneration and complicate healing. Currently, treatment relies on optimizing healing factors rather than administering effective targeted therapies. Owing to their enormous diversity in structure and function, peptides are among the most prevalent and biologically important class of compounds and have been investigated for their wound healing bioactivities. A class of these peptides, called cyclic peptides, confer stability and improved pharmacokinetics, and are an ideal source of wound healing therapeutics. This review provides an overview of cyclic peptides that have been shown to promote wound healing in various tissues and in model organisms. In addition, we describe cytoprotective cyclic peptides that mitigate ischemic reperfusion injuries. Advantages and challenges in harnessing the healing potential for cyclic peptides from a clinical perspective are also discussed. Cyclic peptides are a potentially attractive category of wound healing compounds and more research in this field could not only rely on design as mimetics but also encompass de novo approaches as well.
Toeing the line between regeneration and fibrosis
Authors: Jou Vivian , Lehoczky Jessica A.
Published: June 2023

Understanding the remarkable capacity of vertebrates to naturally regenerate injured body parts has great importance for potential translation into human therapeutic applications. As compared to other vertebrates, mammals have low regenerative capacity for composite tissues like the limb. However, some primates and rodents can regenerate the distal tips of their digits following amputation, indicating that at least very distal mammalian limb tissues are competent for innate regeneration. It follows that successful digit tip regenerative outcome is highly dependent on the location of the amputation; those proximal to the position of the nail organ do not regenerate and result in fibrosis. This distal regeneration versus proximal fibrosis duality of the mouse digit tip serves as a powerful model to investigate the driving factors in determining each process. In this review, we present the current understanding of distal digit tip regeneration in the context of cellular heterogeneity and the potential for different cell types to function as progenitor cells, in pro-regenerative signaling, or in moderating fibrosis. We then go on to discuss these themes in the context of what is known about proximal digit fibrosis, towards generating hypotheses for these distinct healing processes in the distal and proximal mouse digit.
Assessment and diagnosis of right ventricular failure—retrospection and future directions
Authors: Ro Sun Kyun , Sato Kei , Ijuin Shinichi , Sela Declan , Fior Gabriele , Heinsar Silver , Kim Ji Young , Chan Jonathan , Nonaka Hideaki , Lin Aaron C. W. , Bassi Gianluigi Li , Platts David G. , Obonyo Nchafatso G. , Suen Jacky Y. , Fraser John F.
Published: June 2023

The right ventricle (RV) has a critical role in hemodynamics and right ventricular failure (RVF) often leads to poor clinical outcome. Despite the clinical importance of RVF, its definition and recognition currently rely on patients’ symptoms and signs, rather than on objective parameters from quantifying RV dimensions and function. A key challenge is the geometrical complexity of the RV, which often makes it difficult to assess RV function accurately. There are several assessment modalities currently utilized in the clinical settings. Each diagnostic investigation has both advantages and limitations according to its characteristics. The purpose of this review is to reflect on the current diagnostic tools, consider the potential technological advancements and propose how to improve the assessment of right ventricular failure. Advanced technique such as automatic evaluation with artificial intelligence and 3-dimensional assessment for the complex RV structure has a potential to improve RV assessment by increasing accuracy and reproducibility of the measurements. Further, noninvasive assessments for RV-pulmonary artery coupling and right and left ventricular interaction are also warranted to overcome the load-related limitations for the accurate evaluation of RV contractile function. Future studies to cross-validate the advanced technologies in various populations are required.
Lessons that can be learned from the SARS-CoV-2 pandemic and their impact on the prophylaxis and treatment development for neglected tropical arboviruses
Authors: Rosa-Nunes Danilo , Lucchi Danilo B. M. , Andreata-Santos Robert , Janini Luiz Mario R. , Braconi Carla Torres
Published: June 2023

In the 21st Century, emergence and re-emergence of infectious diseases is significant and has an increasing importance in global concern of public health. Based on the COVID-19 pandemic and recently reported epidemics, most human pathogens originate in zoonosis. Many of such pathogens are related to viruses that have RNA genomes, which can be presented structurally as a single-strand or double-strand. During the last two decades, a timeline of major RNA viruses emergencies can be exemplified, such as Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) in 2003, influenza A virus (H1N1) pdm09 in 2009, Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, Ebola virus (EBOV) in 2013–2016, Zika virus (ZIKV) in 2015 and the SARS-CoV-2 pdm19 in 2019. Even so, prophylactic or therapeutic drugs are unavailable for many RNA viruses circulating. Nonetheless, the COVID-19 pandemic brought considerable scientific advances in accelerating progress regarding prophylaxis, antiviral and drug development, and novel treatments. Regarding RNA virus diseases for humans, arboviruses play an essential and neglected role, constantly reemerging and affecting almost half of the human population, for which no drug has been licensed. Here we review the consolidated RNA viruses’ emergence and re-emergence in the 21st Century through available data. Then, we explored valuable lessons gained during the SARS-CoV-2 pandemic and focused on potential epidemiologic updates, prophylaxis, available treatments, and viral drug inhibitors. Finally, we explore arbovirus’s significance and the ongoing development of effective vaccines, antiviral drugs, and novel therapeutic approaches as strategies to control these neglected tropical diseases (NTD).
Intelligent tunnelling robot system for deep-buried long tunnels
Authors: Zhang Qinglong , Zhu Yanwen , Ma Rui , Du Sanlin , Shao Kun , Jing Liujie , Zhang Yongsheng , Li Qingbin
Published: June 2023

Existing tunnel boring machine (TBM) construction presents certain shortcomings. These include difficulty in comprehensive perception of information, poor timelines of information transmission and storage systems, significant effects of traditional data processing methods on the timeless of intelligent decision-making, and poor applicability of decision-making models and control strategies. In addition, the integration level of perception, decision-making, and control should be further improved. Therefore, a cross-platform deployable intelligent tunnelling robot system with closed-loop intelligent control functions of a “comprehensive perception, dual-driven decision-making, and composite intelligent control” is developed. Based on fieldbus, communication, database, cloud computing, and advanced exploration technologies, a multi-source information perception and integrated management platform based on a two-layer architecture is built to achieve the comprehensive perception of tunnelling information. In addition, an optimal decision-making method of the particle swarm optimisation (PSO) algorithm is simultaneously proposed for the minimum decision-making of tunnelling specific energy for scientific analyses and decision-making. A composite intelligent control strategy comprising multimodal and expert experienced learning control strategies is designed to achieve the control of conventional and unfavourable geological sections, respectively. Engineering cases verified the effectiveness and reliability of the intelligent tunnelling robot system. The research results not only provide new ideas and technical means for achieving the less-manned, unmanned, and intelligent tunnelling construction of deep-buried long tunnels but can also be promoted owing to its universality.
An integral assessment of landslide dams generated by the occurrence of rainfall-induced landslide and debris flow hazard chain
Authors: Ortiz-Giraldo Laura , Botero Blanca A. , Vega Johnny
Published: June 2023

Landslides caused by rainfall are one of the most frequent causes of disasters in tropical countries and mountainous terrain and can block rivers generating landslide dams. This paper presents a methodology for the estimation of the obstruction of water streams generated by rainfall-induced shallow landslides. The spatial distribution of the landslide hazard was estimated in terms of the Factor of Safety (FoS) values using the deterministic method with physical basis SLIDE (Slope - Infiltration - Distributed Equilibrium). The rainfall regimes of the study area were estimated by means of a simple scaling Log Normal Model. Subsequently, the resulting areas with a high hazard level that could detach and reach the riverbed were identified as sources for the simulation of the debris flow runout using the Rapid Mass Movement Simulation model with its debris flow module, (i.e., RAMMS-DF), estimating zones of the riverbed that should be analyzed in detail. Finally, the effects of river channel obstructions generated after debris flow movement were analyzed by means of the Iber, a well-known, physically based 2D hydraulic model and their possible changes on the river hydraulic. In order to generate a workflow that allows the application of the SLIDE methodology and the preparation of inputs for the subsequent processes of debris flow propagation and hydraulic modeling of the river corridor of analysis, a Python-based toolbox was created. Our results highlight the changes in the fluvial dynamics in the corridor of the river of analysis after the landslide dams generated by the occurrence of rainfall-induced landslide and debris flow hazard chain for the different return periods. In all cases, the material deposited in the river channel was sufficient to change the hydraulic regime of the river corridor, showing longer delay times in the transit of the flow, in addition to the decrease in the specific flow. This would imply a water shortage in the study basin of the hydroelectric project; however, in the scope of this project it is not possible to really determine the real effects that could be generated by this event.
Technology-based solutions for behavior monitoring: lessons learned
Authors: Pandria Niki , Bamidis Panagiotis D.
Published: June 2023

Introduction

Children’s behavior is indicative of adaptation to early-age development. Adaptive difficulties linked to behavioral difficulties are frequent among school-aged children having a multi-level impact. Five key approaches have been used therapeutically while systematic behavior monitoring has been used to evaluate the efficacy of different interventions. The inherent barriers of traditional monitoring tools have led to the need to design and implement new approaches.

Methods

Four case study series (S1–S4) focused on vulnerable populations are described. Eight participants with different medical backgrounds underwent an intervention, either cognitive training (BrainHQ) (seven out of eight) or operant conditioning strategies. Targeted behaviors were monitored in six out of eight participants using the WHAAM application which could also measure the effectiveness of the intervention applied, while emotional fluctuations were evaluated in two out of eight participants using AffectLecture. Moreover, a 5th pilot study (S5) is included focusing on the early detection and management of ADHD using a serious game-based platform.

Results

In S1, monitoring highlighted that BrainHQ training resulted in positive changes in all but one of the behaviors in Case 1. Studies that exploited the AffectLecture application indicated that emotional state was improved after training, and it was positively correlated with performance in cognitive exercises. The performance in cognitive training was positively correlated with the emotional state before training in S2 but not in S3. A positive correlation between the change in emotional state and performance was mentioned only in S3. Educational and social benefits as well as a positive correlation between the performance and the length of training were reported in both studies. Operant conditioning strategies in S4 resulted in positive behavioral effects in most participants. Preliminary analysis of S5 indicated that the platform has a considerable capacity to discriminate users based on their in-game patterns as ADHD or non-ADHD.

Discussion

The mixture of studies presented in this article incorporates different technological solutions for monitoring or intervening in developmental disorders and behavioral difficulties. Despite the inherent inhomogeneity of such an endeavor, they all highlight the positive prospects of using technology to enhance the educational arsenal of facing behavioral and learning difficulties.
Genetic algorithm optimization for parametrization, digital twinning, and now-casting of unknown small- and medium-scale PV systems based only on on-site measured data
Authors: Guzman Razo Dorian Esteban , Madsen Henrik , Wittwer Christof
Published: June 2023

Accurately predicting and balancing energy generation and consumption are crucial for grid operators and asset managers in a market where renewable energy is increasing. To speed up the process, these predictions should ideally be performed based only on on-site measured data and data available within the monitoring platforms, data which are scarce for small- and medium-scale PV systems. In this study, we propose an algorithm that can now-cast the power output of a photovoltaic (PV) system with high accuracy. Additionally, it offers physical information related to the configuration of such a PV system. We adapted a genetic algorithm-based optimization approach to parametrize a digital twin of unknown PV systems, using only on-site measured PV power and irradiance in the plane of array. We compared several training datasets under various sky conditions. A mean deviation of −1.14 W/kWp and a mean absolute percentage deviation of 1.81% were obtained when we analyzed the accuracy of the PV power now-casting for the year 2020 of the 16 unknown PV systems used for this analysis. This level of accuracy is significant for ensuring the efficient now-casting and operation of PV assets.
Using bacterial pan-genome-based feature selection approach to improve the prediction of minimum inhibitory concentration (MIC)
Authors: Yang Ming-Ren , Su Shun-Feng , Wu Yu-Wei
Published: June 2023

Background: Predicting the resistance profiles of antimicrobial resistance (AMR) pathogens is becoming more and more important in treating infectious diseases. Various attempts have been made to build machine learning models to classify resistant or susceptible pathogens based on either known antimicrobial resistance genes or the entire gene set. However, the phenotypic annotations are translated from minimum inhibitory concentration (MIC), which is the lowest concentration of antibiotic drugs in inhibiting certain pathogenic strains. Since the MIC breakpoints that classify a strain to be resistant or susceptible to specific antibiotic drug may be revised by governing institutes, we refrained from translating these MIC values into the categories “susceptible” or “resistant” but instead attempted to predict the MIC values using machine learning approaches.

Results: By applying a machine learning feature selection approach on a Salmonella enterica pan-genome, in which the protein sequences were clustered to identify highly similar gene families, we showed that the selected features (genes) performed better than known AMR genes, and that models built on the selected genes achieved very accurate MIC prediction. Functional analysis revealed that about half of the selected genes were annotated as hypothetical proteins (i.e., with unknown functional roles), and that only a small portion of known AMR genes were among the selected genes, indicating that applying feature selection on the entire gene set has the potential of uncovering novel genes that may be associated with and may contribute to pathogenic antimicrobial resistances.

Conclusion: The application of the pan-genome-based machine learning approach was indeed capable of predicting MIC values with very high accuracy. The feature selection process may also identify novel AMR genes for inferring bacterial antimicrobial resistance phenotypes.
Population genetic assessment of Viburnum japonicum in China using ddRAD-seq
Authors: Zhu Hong , Liu Juan , Gao Meirong , Yue Chunlei , Li Hepeng
Published: June 2023

Viburnum japonicum is a rare plant species and endemic to the coastal region of Eastern Asia with extremely small populations. Within mainland China, this species can be only found in narrow habitats of the northeast coastal islands of Zhejiang Province. However, there are scarce conservation genetic studies on V. japonicum, which has limited the effective conservation and management of this rare species. Here, 51 individuals in four natural populations covering the Chinese geographic range of the species were sampled to assess the genetic diversity and population structure. A total of 445,060 high-quality single nucleotide polymorphisms (SNPs) were identified using double digest restriction-site associated sequencing (ddRAD-seq). The overall average values of observed heterozygosity (Ho), expected heterozygosity (He), and average nucleotide diversity (π), were 0.2207, 0.2595, and 0.2741, respectively. The DFS-2 population exhibited the highest level of genetic diversity among all the populations. Genetic differentiation between populations was moderate (FST = 0.1425), and there was selfing between populations (FIS = 0.1390, S = 24.52%). Of the total genetic variation, 52.9% was found among populations through AMOVA analysis. The Mantel test (r = 0.982, p = 0.030) combined with analyses of the Maximum Likelihood (ML) phylogenetic tree, ADMIXTURE, and principal component analysis (PCA), revealed that populations of V. japonicum were genetically segregated and significantly correlated with their geographical distribution. Our study demonstrated that V. japonicum maintained a medium level of genetic diversity and differentiation with a strong population structure, and the results were mainly affected by its island distribution pattern and self-crossing characteristics. These results provide insights into the genetic diversity and population history of V. japonicum, critical information for conserving and sustainably developing its genetic resources.
Prediction of small molecule drug-miRNA associations based on GNNs and CNNs
Authors: Niu Zheyu , Gao Xin , Xia Zhaozhi , Zhao Shuchao , Sun Hongrui , Wang Heng , Liu Meng , Kong Xiaohan , Ma Chaoqun , Zhu Huaqiang , Gao Hengjun , Liu Qinggong , Yang Faji , Song Xie , Lu Jun , Zhou Xu
Published: June 2023

MicroRNAs (miRNAs) play a crucial role in various biological processes and human diseases, and are considered as therapeutic targets for small molecules (SMs). Due to the time-consuming and expensive biological experiments required to validate SM-miRNA associations, there is an urgent need to develop new computational models to predict novel SM-miRNA associations. The rapid development of end-to-end deep learning models and the introduction of ensemble learning ideas provide us with new solutions. Based on the idea of ensemble learning, we integrate graph neural networks (GNNs) and convolutional neural networks (CNNs) to propose a miRNA and small molecule association prediction model (GCNNMMA). Firstly, we use GNNs to effectively learn the molecular structure graph data of small molecule drugs, while using CNNs to learn the sequence data of miRNAs. Secondly, since the black-box effect of deep learning models makes them difficult to analyze and interpret, we introduce attention mechanisms to address this issue. Finally, the neural attention mechanism allows the CNNs model to learn the sequence data of miRNAs to determine the weight of sub-sequences in miRNAs, and then predict the association between miRNAs and small molecule drugs. To evaluate the effectiveness of GCNNMMA, we implement two different cross-validation (CV) methods based on two different datasets. Experimental results show that the cross-validation results of GCNNMMA on both datasets are better than those of other comparison models. In a case study, Fluorouracil was found to be associated with five different miRNAs in the top 10 predicted associations, and published experimental literature confirmed that Fluorouracil is a metabolic inhibitor used to treat liver cancer, breast cancer, and other tumors. Therefore, GCNNMMA is an effective tool for mining the relationship between small molecule drugs and miRNAs relevant to diseases.
Tribological behaviors of Ta-10W alloy at elevated temperature
Authors: Xia Haiqing , Xu Yi , Duan Jing , Li Shaoxuan , Jiang Nan , Zhu Shuai , Lei Yaping , Shi Pengfei , Tang Jiancheng
Published: June 2023

Ta-10W alloy has great potential in the aerospace and nuclear industries due to its good formability, high melting point and excellent high-temperature strength. The purpose of this study was to experimentally research the tribological behaviors of Ta-10W at elevated temperatures and the effects of temperatures on the friction coefficient and the wear rate of Ta-10W in sliding wear. It was found that the main wear mechanism of the material at 100°C was abrasive wear, as well as adhesive wear and slight oxidative wear occurred at 200°C and 300°C. The friction coefficients increased as the temperature rose, which was attributed to the increase in metal viscosity at elevated temperatures. The wear rate gradually decreased with the temperature rising, such that there was a conversion from severe wear to light wear. At 200°C and 300°C, a large amount of stable oxide film covered the scar surface, resulting in decreased wear rate.
Case report: A case of epidermolysis bullosa acquisita with IgG and IgM anti-basement membrane zone antibodies relapsed after COVID-19 mRNA vaccination
Authors: Minakawa Satoko , Matsuzaki Yasushi , Yao Shogo , Sagara Chihiro , Akasaka Eijiro , Koga Hiroshi , Ishii Norito , Hashimoto Takashi , Sawamura Daisuke
Published: June 2023

We report a case of autoimmune bullous disease (AIBD) with IgG and IgM autoantibodies against epidermal basement membrane zone (BMZ), which showed recurrence of mucocutaneous lesions after coronavirus disease 2019 (COVID-19) mRNA vaccination. A 20-year-old Japanese woman with a 4-year history of epidermolysis bullosa acquisita (EBA) presented to our clinic. She noticed fever and rash on the same day and visited at our hospital 2 days later. Physical examination revealed blisters, erosions and erythema on the face, shoulder, back, upper arms, and lower lip. A skin biopsy from the forehead showed subepidermal blister. Direct immunofluorescence showed linear depositions of IgG, IgM, and C3c in the epidermal BMZ. By indirect immunofluorescence of 1M NaCl-split normal human skin, circulating IgG autoantibodies were bound to the dermal side of the split at 1:40 serum dilution, and circulating IgM antibodies were bound to the epidermal side of the spilt. After the increase of prednisolone dose to 15 mg/day, the mucocutaneous lesions resolved in a week. The present case is the first case of possible EBA with IgG and IgM anti-BMZ antibodies, in which the mucocutaneous lesions were recurred after COVID-19 mRNA vaccination. Clinicians should be aware that bullous pemphigoid-like AIBDs, including EBA and IgM pemphigoid, might be developed after COVID-19 mRNA vaccination.
Predictive value of cell population data with Sysmex XN-series hematology analyzer for culture-proven bacteremia
Authors: Miyajima Yuki , Niimi Hideki , Ueno Tomohiro , Matsui Atsushi , Higashi Yoshitsugu , Kojima Nozomi , Kono Mari , Iwasaki Yosuke , Nagaoka Kentaro , Yamamoto Yoshihiro , Kitajima Isao
Published: June 2023

Background

Cell population data (CPD) parameters related to neutrophils, such as fluorescent light intensity (NE-SFL) and fluorescent light distribution width index (NE-WY), have emerged as potential biomarkers for sepsis. However, the diagnostic implication in acute bacterial infection remains unclear. This study assessed the diagnostic value of NE-WY and NE-SFL for bacteremia in patients with acute bacterial infections, and those associations with other sepsis biomarkers.

Methods

Patients with acute bacterial infections were enrolled in this prospective observational cohort study. For all patients, a blood sample, with at least two sets of blood cultures, were collected at the onset of infection. Microbiological evaluation included examination of the blood bacterial load using PCR. CPD was assessed using Automated Hematology analyzer Sysmex series XN-2000. Serum levels of procalcitonin (PCT), interleukin-6 (IL-6), presepsin, and CRP were also assessed.

Results

Of 93 patients with acute bacterial infection, 24 developed culture-proven bacteremia and 69 did not. NE-SFL and NE-WY were significantly higher in patients with bacteremia than in those without bacteremia (p < 0.005, respectively), and were significantly correlated with the bacterial load determined by PCR (r = 0.384 and r = 0.374, p < 0.005, respectively). To assess the diagnostic value for bacteremia, receiver operating characteristic curve analysis was used. NE-SFL and NE-WY showed an area under the curve of 0.685 and 0.708, respectively, while those of PCT, IL-6, presepsin, and CRP were 0.744, 0.778, 0.685, and 0.528, respectively. Correlation analysis showed that the levels of NE-WY and NE-SFL were strongly correlated with PCT and IL-6 levels.

Conclusion

This study demonstrated that NE-WY and NE-SFL could predict bacteremia in a manner that may be different from that of other indicators. These findings suggest there are potential benefits of NE-WY/NE-SFL in predicting severe bacterial infections.
Involvement of the European Medicines Agency in multi-stakeholder regulatory science research projects: experiences of staff members and project coordinators
Authors: Saesen Robbe , Machado Matilde , Crifo Bianca , Liu Lifang , de Vries Corinne , Herold Ralf , Llinares Garcia Jordi , Huys Isabelle
Published: June 2023

Background

The European Medicines Agency (EMA) interacts with many different stakeholders involved in the development of drugs, including academic researchers. In recent years, EMA has collaborated more closely with academia, inter alia by taking part in external research projects such as those set up under the Horizon 2020 program in general and the Innovative Medicines Initiative in particular. The aim of this study was to evaluate the perceived added value of EMA’s involvement in these projects, both from the perspective of the Agency’s participating Scientific Officers and of the coordinators of the consortia that undertook them.

Methods

Semi-structured interviews were conducted with the coordinators of 21 ongoing or recently finalized projects in which EMA has participated, as well as with the Agency experts contributing to them.

Results

In total, 40 individuals were interviewed, of whom 23 were project coordinators and 17 were EMA staff members. While most of the projects were reported to suffer from delays due to the SARS-CoV-2 pandemic, the consortia adapted to the circumstances and their members still expected to deliver on their objectives. EMA’s input into the projects ranged from providing guidance by reviewing documents and attending meetings to creating project materials and disseminating them. The frequency of communication between EMA and the consortia varied widely. The projects generated a diverse set of outputs, which encompassed new or improved medicinal products, methodological standards, research infrastructures, and educational tools. All of the coordinators expressed that EMA’s contributions to their projects had increased the scientific relevance of their consortium’s work, and the EMA experts found that the knowledge and the deliverables produced by the projects were valuable, taking into consideration the time they had invested into them. In addition, interviewees highlighted some actions which could be taken to increase the regulatory significance of the project outcomes.

Conclusion

EMA’s engagement in external research projects benefits the consortia conducting them and supports the Agency’s mission to foster scientific excellence and advance regulatory science.
Multimodality imaging evaluation of primary testicular extranodal natural killer/T-cell lymphoma: two case reports
Authors: Huang Wenpeng , Liu Xiaonan , Li Liming , Zhang Yongbai , Gao Yuan , Gao Jianbo , Kang Lei
Published: June 2023

Background

Extranodal natural killer/T-cell lymphoma (ENKTCL) is a distinct pathological entity and accounts for ~10% of T-cell lymphomas. The histological features of ENKTCL include angiodestruction and coagulative necrosis and the association with EBV infection. ENKTCL is typically aggressive and mainly affects the nasal cavity and nasopharyngeal region. However, some patients can present with distant nodal or extranodal involvement such as the Waldeyer ring, gastrointestinal tract, genitourinary organs, lung, thyroid, skin, and testes. Compared to ENKTCL of nasal type, primary testicular ENKTCL is very rare and has a lower age of onset and faster clinical progression, with tumor cell dissemination occurring early in the disease.

Case report

Case 1: A 23-year-old man presented with 1 month of right testicular pain and swelling. Enhancement CT revealed increased density in the right testis, uneven increased enhancement, discontinuity of the local envelope, and multiple trophoblastic vessels in the arterial phase. Testicular ENKTCL was diagnosed by post-operative pathology. The patient underwent a follow-up 18F-FDG PET/CT imaging 1 month later and found elevated metabolism in the bilateral nasal, left testicular, and right inguinal lymph nodes. Unfortunately, the patient received no further treatment and died 6 months later. Case 2: A 2-year-old male child presented with an enlarged right testicle, MRI showed a mass in the right epididymis and testicular area, which showed low signal on T1WI, high signal on T2WI and DWI, and low signal on ADC. Meanwhile, CT showed soft tissue in the lower lobe of the left lung and multiple high-density nodules of varying sizes in both lungs. Based on the post-operative pathology, the lesion was diagnosed with primary testicular ENKTCL. The pulmonary lesion was diagnosed as hemophagocytic lymphohistiocytosis associated with EBV infection. The child was given SMILE chemotherapy, but pancreatitis was induced during chemotherapy, then he died 5 months later after chemotherapy.

Conclusion

Primary testicular ENKTCL is very rare in clinical practice, typically presenting as a painful testicular mass, which can mimic inflammatory lesions and cause diagnostic challenges. 18F-FDG PET/CT plays pivotal roles in the diagnosis, staging, evaluation of treatment outcomes and prognosis evaluation in patients with testicular ENKTCL, and it is helpful to assist clinical practice to better formulate individualized treatment plans.
SARS-CoV-2 and gastrointestinal diseases
Authors: Sha Ailong , Liu Yi , Zhao Xuewen
Published: June 2023

Background

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative agent of the novel coronavirus disease (COVID-19) pandemic, which has caused serious challenges for public health systems worldwide.

Literature review

SARS-CoV-2 invades not only the respiratory system, but also the digestive system, causing a variety of gastrointestinal diseases.

Significance

Understanding the gastrointestinal diseases caused by SARS-CoV-2, and the damage mechanisms of SARS-CoV-2 to the gastrointestinal tracts and gastrointestinal glands are crucial to treating the gastrointestinal diseases caused by SARS-CoV-2.

Conclusion

This review summarizes the gastrointestinal diseases caused by SARS-CoV-2, including gastrointestinal inflammatory disorders, gastrointestinal ulcer diseases, gastrointestinal bleeding, and gastrointestinal thrombotic diseases, etc. Furthermore, the mechanisms of gastrointestinal injury induced by SARS-COV-2 were analyzed and summarized, and the suggestions for drug prevention and treatment were put forward for the reference of clinical workers.
Energy-based generative models for target-specific drug discovery
Authors: Li Junde , Beaudoin Collin , Ghosh Swaroop
Published: June 2023

Drug targets are the main focus of drug discovery due to their key role in disease pathogenesis. Computational approaches are widely applied to drug development because of the increasing availability of biological molecular datasets. Popular generative approaches can create new drug molecules by learning the given molecule distributions. However, these approaches are mostly not for target-specific drug discovery. We developed an energy-based probabilistic model for computational target-specific drug discovery. Results show that our proposed TagMol can generate molecules with similar binding affinity scores as real molecules. GAT-based models showed faster and better learning relative to Graph Convolutional Network baseline models.