bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular dynamics simulation on the shielding effect of aminopropyl trimethoxysilane film on corrosive media
Authors: Wang Xin-jie , Li Yan , Xia Lei , Li Na , Zhang Ao-ran , Zhang Hong-mei , Jiang Zheng-yi
Published: August 2023

Aminopropyl trimethoxysilane (APTMS) was used as a silane reagent, and oxygen and water were set as corrosion media, respectively. The mean square displacement (MSD) of oxygen and water molecules in silanized films with different cross-linking degrees (APTMS-OH-1, APTMS-OH-4, APTMS-OH-8, and APTMS-OH-12) were investigated by molecular dynamics simulation to characterize the corrosion inhibition effect of silanized films in different corrosion media. The results showed that compared with in air, the MSD of oxygen and water molecules in silane film was significantly reduced, which indicated that silane film could prevent the diffusion of corrosive medium, thus protecting material. Silane films with various crosslinking degrees have different shielding effects on oxygen and water molecules. The MSD of oxygen in silane films with different crosslinking degrees was: APTMS-OH-1>APTMS-OH-4>APTMS-OH-12>APTMS-OH-8, while the MSD of water in silane films with different crosslinking degrees was: APTMS-OH-1>APTMS-OH-4≈APTMS-OH-12>APTMS-OH-8. The MSD of both oxygen and water molecules was the lowest in silane films with a crosslinking degree of 8, which showed that silane films had the highest shielding effect.
The Performance of the Improved Clay Soil on Road Subgrade
Authors: Liu Jia , Wang Hailin , Tian Yu
Published: August 2023

The poor fillings of embankments cause insufficient strength and excessive deformation to road subgrade. This study took a kind of onsite over-wet red clay soil as the research sample with lime and cement as additives to improve it, which could be used as the subgrade filling. Laboratory experiments scanning electron microscopy (SEM), California bearing ratio (CBR), water absorption, and unconfined compressive strength (UCS) were conducted to analyze the performance of the improved soil. The results showed that the improved clay soil had rich fibrous components, enabling the UCS values of the improved soil to reach greater than 0.6 MPa on average at 6% proportion by weight, which meant a higher strength compared to plain soil. The variation of maximum dry density value and optimum water content value on compaction curves indicated that the improved red clay soil could reduce its sensitivity to water, making it easy to be compacted. With the increase in additive proportion, the CBR values increased while water absorption potential decreased significantly, showing that the improved soil was likely to hold stable humidity for the subgrade without becoming too humid or too dry. The application to road subgrade in the field proved good practicability and performance of the improved clay soil.
Simulation study of machining deformation under different machining strategies of 7055 aluminum plate
Authors: Li Yang , Li Yanan , Yan Hongwei , Shi Guohui , Li Ying
Published: August 2023

In this research, the finite element approach was used to investigate the influence of machining type and machining sequence on the machining deformation of a 7055 aluminum alloy thick plate with an initial residual stress condition. The results reveal that the frame-first machining type produces much less machining distortion than the layer-first machining type. The machining distortion of the thick plate with the end-first connection with the frame-first machining sequence is the smallest. By developing an appropriate machining strategy, the machining distortion of the thick plate may be successfully decreased.
Corrosion Mechanism of Typical Shale Gas Gathering and Transportation Pipelines in Southwest China
Authors: Sun Ming , Cui Wei , Lin Nan
Published: August 2023

The shale gas surface gathering and transportation pipeline in southwest China has experienced serious internal corrosion, which affects the production of shale gas wells and has great potential safety hazards. To find out the corrosion type and corrosion mechanism, the corrosion analysis and mechanism research of gathering and transportation pipelines are carried out, including corrosion morphology observation, corrosion product analysis, fluid mechanics calculation, etc. The results show that the corrosion products of the gathering and transportation pipeline are mainly FeCO3 with high S content, and the corrosion type is sulfate-reducing bacteria (SRB) and CO2 corrosion. At the same time, the corrosion pits are mainly distributed on the approach stream side, which is closely related to the scouring effect of the medium flow in the vertical branch pipe on the wall surface of the tee. The corrosion weight loss test shows that the corrosion rate of sterile solution is significantly lower than that of bacterium solution, indicating that the presence of SRB significantly expedites the corrosion of materials.
Simulation Study of Composite Insulator Material Defects Based on Microwave Detection
Authors: Xiao Chi , Li Junlin , Wang Pei , Liu Junjie , Zhang Qiwen
Published: August 2023

Glass Fiber Reinforced Polymer (GFRP) is a kind of raw material used in the manufacture of composite insulator mandrels. If crack defects occur in the composite insulator mandrel, it will eventually lead to brittle fractures, which will cause extremely serious accidents. Aiming at detecting the internal defects of GFRP materials by the microwave reflection method, we carried out a numerical modeling analysis adopting the electromagnetic simulation method. Samples with different depths of defects are used for sweep frequency calculation, and the frequency range is from 18 to 26.5 GHz. A simple method for judging defective GFRP boards and non-defective GFRP boards is obtained. In addition, as the depth of the defect increases, the valley value of the S11 signal increases, and at the same time, the absolute value of the phase change of the signal decreases. The simulation results show that the microwave reflection method is feasible for detecting the defects of composite insulator materials.
Study on tool wear state monitoring based on EEMD information entropy and PSO-SVM
Authors: Dong Delong , Wang Tianzhong , Wang Jinhui , Niu Jintao , Qiao Yang , Wang Xiangyu
Published: August 2023

Tool wear state is closely related to the workpiece surface, so tool wear monitoring has an important engineering significance. This paper proposes a tool for wear monitoring means based on EEMD information entropy and PSO-SVM. Firstly, the force signal of the cutting process collected force by the sensor is decomposed by EEMD, and information entropy of the decomposed signal was used as the tool wear feature quantity. Then the PSO-SVM model was used to classify and identify the extracted tool wear feature quantity, and the recognition accuracy of the method was 97.75%. Compared with BP neural network and SVM model without algorithm optimization, it can quickly and accurately identify three types of tool wear states meanwhile realizing monitoring of tool wear state.
Thermal insulation characteristics of high-temperature heat seals for hypersonic aero-engines
Authors: Li Haiping , Cai Huikun , Du Zhihong , You Yancheng , Zhu Chengxiang
Published: August 2023

The high-temperature baseline sealing thermal protection technology is of great significance to realizing hypersonic aero-engines and aircraft. Based on the fact that there are few studies on the high-temperature baseline heat sealing in the ultra-high temperature environment (above 1000 °C), the paper establishes a simulation model to analyze the influence of different characteristic parameters on the thermal protection performance of the heat seal at ultra-high temperature and carried out experiments. Verification, simulation, and experiment error are less than 6%. The research results show that the aluminum silicate fiber has the best thermal insulation effect in the material of the inner thermal insulation layer, and the temperature can be lowered by more than 900 °C under an environment of 1200 °C. It is used to prepare heat seals. In addition, the filling density and thickness of the inner thermal insulation layer have little influence on the thermal insulation effect, and the influence coefficient does not exceed 5%. In the test of the degree of degradation of the thermal insulation performance of the heat seal, it is found that it does not exceed 5%, which meets the requirements for use. This paper further promotes the development of high-temperature thermal protection technology. It can also provide a corresponding technical basis for developing supersonic aero-engines.
Vascular Stents with Controllable Negative Poisson’s Ratio Based on Energy Homogenization Method
Authors: An Ran , Ge Xueyuan , Wang Miaohui
Published: August 2023

Based on the energy uniformization method and topology optimization method, a negative Poisson’s ratio generating model was designed. Using the generated cells, a novel negative Poisson’s ratio vascular stent was designed. A finite element model of the expansion process, including the vessel, stent, and balloon, was established. The analysis results showed an obvious tensile deformation pattern. Based on this expansion model, 23 sample points were sampled using the Latin hypercube method. Material parameters were used as variables, and cell equivalent Poisson’s ratio was used as a response. Least squares regression, moving least squares methods, Kriging, and radial basis function response surface models were established, and the fitted surface patterns were consistent with the design. The equivalent Poisson’s ratio measured by the cell was less than 8% different from the theoretical Poisson’s ratio obtained by uniformization.
Evaluation of different classification methods using electronic nose data to diagnose sarcoidosis
Authors: van der Sar Iris G , van Jaarsveld Nynke , Spiekerman Imme A , Toxopeus Floor J , Langens Quint L , Wijsenbeek Marlies S , Dauwels Justin , Moor Catharina C
Published: August 2023

Electronic nose (eNose) technology is an emerging diagnostic application, using artificial intelligence to classify human breath patterns. These patterns can be used to diagnose medical conditions. Sarcoidosis is an often difficult to diagnose disease, as no standard procedure or conclusive test exists. An accurate diagnostic model based on eNose data could therefore be helpful in clinical decision-making. The aim of this paper is to evaluate the performance of various dimensionality reduction methods and classifiers in order to design an accurate diagnostic model for sarcoidosis. Various methods of dimensionality reduction and multiple hyperparameter optimised classifiers were tested and cross-validated on a dataset of patients with pulmonary sarcoidosis (n = 224) and other interstitial lung disease (n = 317). Best performing methods were selected to create a model to diagnose patients with sarcoidosis. Nested cross-validation was applied to calculate the overall diagnostic performance. A classification model with feature selection and random forest (RF) classifier showed the highest accuracy. The overall diagnostic performance resulted in an accuracy of 87.1% and area-under-the-curve of 91.2%. After comparing different dimensionality reduction methods and classifiers, a highly accurate model to diagnose a patient with sarcoidosis using eNose data was created. The RF classifier and feature selection showed the best performance. The presented systematic approach could also be applied to other eNose datasets to compare methods and select the optimal diagnostic model.
Local strategies towards 100% renewable energy cities and regions for West Nusa Tenggara, Indonesia
Authors: Gokarn Kanak , Steingrube Annette , Sen Rohit
Published: August 2023

Much of the focus in the global transition towards renewable energy, a key steppingstone towards achieving the goals of the Paris Agreement, has been on the national and international levels. This focus tends to hide the immense variation present at the sub-national level. Local and regional governments are critical actors in the energy transition, and their involvement is crucial as they are ideally placed to guide their respective communities and to ensure that this transition is just, equitable and inclusive. Even though they may show the ability and ambition, the need for effective multilevel governance and enabling national policy frameworks to channel resources to the local and regional levels is more urgent than ever. Through the 100% Renewables Cities and Regions Roadmap project, the Province of West Nusa Tenggara (NTB) in Indonesia has chosen to aim to achieve one hundred percent renewable energy use in its territory by 2050 on the way to net-zero emissions. This paper discusses the results of the energy systems modelling conducted in NTB that presents a viable pathway towards this goal, which forms the basis of further recommendations and ways forward for the province in terms of priority sectors and actions.
Chemical components from the bark layers of Eucalyptus pellita F Muell.
Authors: Andika R , Himmi SK , Ismayati M , Sari RK , Arinana A , Tjahyono B , Tarmadi D , Guswenrivo I , Adi DS , Imanullah A , Krishanti NPRA , Iqbal A , Tobimatsu Y , Yusuf S
Published: August 2023

The utilization of E. pellita bark as waste is still not widely carried out due to a lack of information about the chemical content. Therefore, the current study aimed to analyze the chemical content of the bark of E. pellita using pyrolysis-gas chromatography-mass spectrometry (PyGCMS). The results showed the total extractive content of E. pellita’s inner bark, outer bark, and mix-bark was 12.17%, 16.19%, and 14.85%, respectively. The holocellulose content of E. pellita mix-bark was 65.45%, while the inner bark and outer bark were 60.68% and 59.29%, respectively. The alpha-cellulose content of E. pellita bark was 57.97%, while the inner and outer barks were 56.43% and 54.14%; the lignin content of the clason mix-bark of E. pellita was 25.39%, and for the inner bark and outer bark were 28% and 26.72%, respectively. The results of pyGCMS showed that the extractives of the bark of E. pellita were catechol, 3-methyl-catechol, resorcinol, 3,5-Dimethoxy-4-hydroxytoluene, and (E)-3,3′-Dimethoxy-4,4′-dihydroxystilbene
Aligning “Energy Culture” as Part of Sustainable Tourism Ideas
Authors: Rudiany NP , Isnarti R , Ramadhan I , Kusumawardhana I
Published: August 2023

The idea of sustainable tourism is closely related to the aspects of the economy, environment and socio-cultural. In short, sustainable tourism aims to economically empower the people in potential tourism areas without disturbing the balance of natural biodiversity and the established social relations among them. Along with sustainable tourism development, governments are also eager to speed up the use of renewable energy in tourism sites. However, the government tends to increase the installation of modern infrastructure to produce renewable energy for tourist areas. As a consequence, the development of sustainable tourism requires more budget and technical coordination between stakeholders, while it might affect the safety of local people. This research proposes the term “energy culture” as an integral part of sustainable tourism. In this concept, the related parties shall encourage the utilization of the energy source from local potential. This energy culture will strengthen the value of sustainability in developing tourist attractions. It helps preserve the material culture of energy, norms, and practices to provide a sustainable energy source to the people.
Synthesis and characterization of liposomes encapsulating silver nanoprisms obtained by millifluidic-based production for drug delivery
Authors: Yanar Fatih , Kimpton Harriet , Cristaldi Domenico Andrea , Mosayyebi Ali , Carugo Dario , Zhang Xunli
Published: August 2023

Silver nanoprisms (SNPs) have attracted significant attention due to their surface plasmon resonance behaviour, which is strongly dependent on their size and shape. The enhanced light absorption and scattering capacity of SNPs, make them a promising candidate system for non-invasive imaging and drug delivery in nanoparticle-assisted diagnostics and therapy. However, systemic administration of silver nanoparticles (AgNPs) at high concentrations may result in toxic side-effects, arising from non-targeted bio-distribution. These drawbacks could be mitigated by employing liposomes as carriers for AgNPs. However, there is a lack of systematic studies on production and subsequent physico-chemical characterisation of liposomal systems encapsulating SNPs. The present study therefore investigated the synthesis of liposomes encapsulating SNPs (Lipo/SNPs) using a continuous-flow millimetre-scale reactor, whereby liposome formation was governed by a solvent exchange mechanism. An aqueous phase and an ethanolic lipid phase were conveyed through two separate inlet channels, and subsequently travelled through a serpentine-shaped channel where mixing between the two phases took place. The synthesis process was optimised by varying both liposome formulation and the operating fluidic parameters, including the ratio between inlet flow rates (or flow rate ratio) and the total flow rate. The obtained Lipo/SNPs were characterised for their size and electrostatic charge, using a dynamic light scattering apparatus. Liposome morphology and encapsulation efficiency of SNPs within liposomes were determined by transmission electron microscopy (TEM) imaging. The synthesised negatively charged Lipo/SNP samples were found to have an average size of ∼150 nm (size dispersity < 0.3). The AgNPs encapsulation efficiency was equal to 77.48%, with mostly single SNPs encapsulated in liposomes. By using a multiangle TEM imaging approach, quasi-3D images were obtained, further confirming the encapsulation of nanoparticles within liposomes. Overall, the formulation and production technique developed in the present study has potential to contribute towards mitigating challenges associated with AgNP-mediated drug delivery and diagnostics.
Functionally graded materials: review on manufacturing by Liquid and gas based techniques
Authors: Ramesh M , Karthik A , Jafrey Daniel James D , Karthik Pandiyan G
Published: August 2023

New materials called functionally graded materials (FGMs) have qualities that gradually alter in relation to their dimensions. This collection of materials represents a significant advancement over earlier composite material. FGM is made up of two or more components that work together to produce the qualities necessary for the intended use. This article provides an overview of the various FGM classifications, fabrication techniques (gas based and liquid based), and applications. The problems associated with the manufacturing of FGM are addressed in the study. This paper also reviews the present state of knowledge in the areas of selection of material, manufacturing process, characterization studies, and modelling of FGM. The potential applications of the FGM, with their advantages and disadvantages, are discussed in this paper. The proposed new primary paths for FGMs research are based on the categories that have been presented and the most recent improvements in analysis and production methods.
Electro-localization method using a muscle conductive phantom for needle position detection towards medical training
Authors: Gomez-Tames Jose , Yu Wenwei
Published: August 2023

Simulation in healthcare can help train, improve, and evaluate medical personnel’s skills. In the case of needle insertion/manipulation inside the muscle during an nEMG examination, a training simulator Requires estimating the position of the needle to output the electrical muscle activity in real time according to the training plan. External cameras can be used to estimate the needle location; however, different error sources can make its implementation difficult and new medical sensing technologies are needed. This study introduces and demonstrates the feasibility of a conductive phantom that serves as the medium for needle insertion and senses the 3D needle position based on a technique named electro-localization for the first time. The proposed conductive phantom is designed so that different voltage distributions are generated in the phantom using electrodes placed on its borders. The needle is inserted in the phantom, and the recorded voltages are mapped to spatial coordinates using a finite element method (FEM)-based computational model of the conductive phantom to estimate the 3D needle tip position. Experimental and simulation results of phantom voltage distributions agreed. In 2D mapping (no depth consideration), the needle position error was 1.7 mm, which was marginally reduced if only the central area of the phantom was used (1.5 mm). In 3D mapping, the error was 4 mm. This study showed the feasibility of using a conductive muscle phantom as a new embedded sensor that estimates needle position for medical training of nEMG without relying on external sensors.
Benchmarking multi-platform sequencing technologies for human genome assembly
Authors: Wang Jingjing , Veldsman Werner Pieter , Fang Xiaodong , Huang Yufen , Xie Xuefeng , Lyu Aiping , Zhang Lu
Published: August 2023

Genome assembly is a computational technique that involves piecing together deoxyribonucleic acid (DNA) fragments generated by sequencing technologies to create a comprehensive and precise representation of the entire genome. Generating a high-quality human reference genome is a crucial prerequisite for comprehending human biology, and it is also vital for downstream genomic variation analysis. Many efforts have been made over the past few decades to create a complete and gapless reference genome for humans by using a diverse range of advanced sequencing technologies. Several available tools are aimed at enhancing the quality of haploid and diploid human genome assemblies, which include contig assembly, polishing of contig errors, scaffolding and variant phasing. Selecting the appropriate tools and technologies remains a daunting task despite several studies have investigated the pros and cons of different assembly strategies. The goal of this paper was to benchmark various strategies for human genome assembly by combining sequencing technologies and tools on two publicly available samples (NA12878 and NA24385) from Genome in a Bottle. We then compared their performances in terms of continuity, accuracy, completeness, variant calling and phasing. We observed that PacBio HiFi long-reads are the optimal choice for generating an assembly with low base errors. On the other hand, we were able to produce the most continuous contigs with Oxford Nanopore long-reads, but they may require further polishing to improve on quality. We recommend using short-reads rather than long-reads themselves to improve the base accuracy of contigs from Oxford Nanopore long-reads. Hi-C is the best choice for chromosome-level scaffolding because it can capture the longest-range DNA connectedness compared to 10× linked-reads and Bionano optical maps. However, a combination of multiple technologies can be used to further improve the quality and completeness of genome assembly. For diploid assembly, hifiasm is the best tool for human diploid genome assembly using PacBio HiFi and Hi-C data. Looking to the future, we expect that further advancements in human diploid assemblers will leverage the power of PacBio HiFi reads and other technologies with long-range DNA connectedness to enable the generation of high-quality, chromosome-level and haplotype-resolved human genome assemblies.
OTTM: an automated classification tool for translational drug discovery from omics data
Authors: Yang Xiaobo , Zhang Bei , Wang Siqi , Lu Ye , Chen Kaixian , Luo Cheng , Sun Aihua , Zhang Hao
Published: August 2023

Omics data from clinical samples are the predominant source of target discovery and drug development. Typically, hundreds or thousands of differentially expressed genes or proteins can be identified from omics data. This scale of possibilities is overwhelming for target discovery and validation using biochemical or cellular experiments. Most of these proteins and genes have no corresponding drugs or even active compounds. Moreover, a proportion of them may have been previously reported as being relevant to the disease of interest. To facilitate translational drug discovery from omics data, we have developed a new classification tool named Omics and Text driven Translational Medicine (OTTM). This tool can markedly narrow the range of proteins or genes that merit further validation via drug availability assessment and literature mining. For the 4489 candidate proteins identified in our previous proteomics study, OTTM recommended 40 FDA-approved or clinical trial drugs. Of these, 15 are available commercially and were tested on hepatocellular carcinoma Hep-G2 cells. Two drugs—tafenoquine succinate (an FDA-approved antimalarial drug targeting CYC1) and branaplam (a Phase 3 clinical drug targeting SMN1 for the treatment of spinal muscular atrophy)—showed potent inhibitory activity against Hep-G2 cell viability, suggesting that CYC1 and SMN1 may be potential therapeutic target proteins for hepatocellular carcinoma. In summary, OTTM is an efficient classification tool that can accelerate the discovery of effective drugs and targets using thousands of candidate proteins identified from omics data. The online and local versions of OTTM are available at http://otter-simm.com/ottm.html.
A denoised multi-omics integration framework for cancer subtype classification and survival prediction
Authors: Pang Jiali , Liang Bilin , Ding Ruifeng , Yan Qiujuan , Chen Ruiyao , Xu Jie
Published: August 2023

The availability of high-throughput sequencing data creates opportunities to comprehensively understand human diseases as well as challenges to train machine learning models using such high dimensions of data. Here, we propose a denoised multi-omics integration framework, which contains a distribution-based feature denoising algorithm, Feature Selection with Distribution (FSD), for dimension reduction and a multi-omics integration framework, Attention Multi-Omics Integration (AttentionMOI) to predict cancer prognosis and identify cancer subtypes. We demonstrated that FSD improved model performance either using single omic data or multi-omics data in 15 The Cancer Genome Atlas Program (TCGA) cancers for survival prediction and kidney cancer subtype identification. And our integration framework AttentionMOI outperformed machine learning models and current multi-omics integration algorithms with high dimensions of features. Furthermore, FSD identified features that were associated to cancer prognosis and could be considered as biomarkers.
Longitudinal imaging highlights preferential basal ganglia circuit atrophy in Huntington’s disease
Authors: Liu Chin-Fu , Younes Laurent , Tong Xiao J , Hinkle Jared T , Wang Maggie , Phatak Sanika , Xu Xin , Bu Xuan , Looi Vivian , Bang Jee , Tabrizi Sarah J , Scahill Rachael I , Paulsen Jane S , Georgiou-Karistianis Nellie , Faria Andreia V , Miller Michael I , Ratnanather J Tilak , Ross Christopher A
Published: August 2023

Huntington’s disease is caused by a CAG repeat expansion in the Huntingtin gene (HTT), coding for polyglutamine in the Huntingtin protein, with longer CAG repeats causing earlier age of onset. The variable ‘Age’ × (‘CAG’—L), where ‘Age’ is the current age of the individual, ‘CAG’ is the repeat length and L is a constant (reflecting an approximation of the threshold), termed the ‘CAG Age Product’ (CAP) enables the consideration of many individuals with different CAG repeat expansions at the same time for analysis of any variable and graphing using the CAG Age Product score as the X axis. Structural MRI studies have showed that progressive striatal atrophy begins many years prior to the onset of diagnosable motor Huntington’s disease, confirmed by longitudinal multicentre studies on three continents, including PREDICT-HD, TRACK-HD and IMAGE-HD. However, previous studies have not clarified the relationship between striatal atrophy, atrophy of other basal ganglia structures, and atrophy of other brain regions. The present study has analysed all three longitudinal datasets together using a single image segmentation algorithm and combining data from a large number of subjects across a range of CAG Age Product score. In addition, we have used a strategy of normalizing regional atrophy to atrophy of the whole brain, in order to determine which regions may undergo preferential degeneration. This made possible the detailed characterization of regional brain atrophy in relation to CAG Age Product score. There is dramatic selective atrophy of regions involved in the basal ganglia circuit—caudate, putamen, nucleus accumbens, globus pallidus and substantia nigra. Most other regions of the brain appear to have slower but steady degeneration. These results support (but certainly do not prove) the hypothesis of circuit-based spread of pathology in Huntington’s disease, possibly due to spread of mutant Htt protein, though other connection-based mechanisms are possible. Therapeutic targets related to prion-like spread of pathology or other mechanisms may be suggested. In addition, they have implications for current neurosurgical therapeutic approaches, since delivery of therapeutic agents solely to the caudate and putamen may miss other structures affected early, such as nucleus accumbens and output nuclei of the striatum, the substantia nigra and the globus pallidus.
Evaluating medical undergraduates’ and dermatology faculty members’ perception of using three-dimensional images as part of dermatology education in a time of COVID-19: a mixed-methods study
Authors: Lim Delwyn Zhi Jie , Lim Yen Loo , Chua Sze-Hon , Lim Ziying Vanessa
Published: August 2023

Background

The coronavirus-19 pandemic has impacted the delivery of medical education in dermatology, leading to decreased patient contact. There arose a need to pioneer innovative teaching tools to augment current methods for now and beyond the pandemic.

Objectives

We aimed to assess the utility of three-dimensional (3D) images in the learning and teaching of dermatology by analysing the perceptions of medical undergraduates and faculty members in a qualitative and quantitative study.

Methods

Medical undergraduates (n = 119) and dermatology faculty members (n = 20) were recruited on a voluntary basis to watch a showcase session using a portable 3D imaging system allowing 3D images of skin lesions to be examined and digitally manipulated. After the session, participants filled in an anonymous questionnaire evaluating their perceptions.

Results

Of the 119 learners, most (> 84%) strongly agreed/agreed that (i) they would have more confidence in the field of dermatology; (ii) their ability to describe skin lesions would increase; (iii) their understanding of common dermatological conditions would increase; (iv) 3D images allow a greater approximation to real-life encounters than 2D images; and (v) learning with this modality would be useful. Of the 20 faculty members, most (> 84%) strongly agreed/agreed that (i) it is easier to teach with the aid of 3D images, and (ii) they would want access to 3D images during teaching sessions. Skin tumours were perceived to be learnt best via this modality in terms of showcasing topography (P < 0.01) and close approximation to real-life (P < 0.001). Overall, thematic analysis from qualitative analysis revealed that conditions learnt better with 3D images were those with surface changes and characteristic topography.

Conclusions

Our results show that the greatest utility of 3D images lies in conditions where lesions have skin surface changes in the form of protrusions or depressions, such as in skin tumours or ulcers. As such, 3D images can be useful teaching tools in dermatology, especially in conditions where appreciation of surface changes and topography is important.
Adalimumab Clearance, Rather Than Trough Level, May Have Greatest Relevance to Crohn’s Disease Therapeutic Outcomes Assessed Clinically and Endoscopically
Authors: Wright Emily K , Chaparro Maria , Gionchetti Paolo , Hamilton Amy L , Schulberg Julien , Gisbert Javier P , Chiara Valerii Maria , Rizzello Fernando , De Cruz Peter , Panetta John C , Everts-van der Wind Annelie , Kamm Michael A , Dervieux Thierry
Published: August 2023

Objective

We postulated that adalimumab [ADA] drug clearance [CL] may be a more critical determinant of therapeutic outcome than ADA concentration. This was tested in Crohn’s disease [CD] patients undergoing ADA maintenance treatment.

Methods

CD patients from four cohorts received ADA induction and started maintenance therapy. Therapeutic outcomes consisted of endoscopic remission [ER], sustained C-reactive protein [CRP] based clinical remission [defined as CRP levels below 3 mg/L in the absence of symptoms], and faecal calprotectin [FC] level below 100 µg/g. Serum albumin, ADA concentration, and anti-drug antibody status were determined using immunochemistry and homogeneous mobility shift assay, respectively. CL was determined using a nonlinear mixed effect model with Bayesian priors. Statistical analysis consisted of Mann–Whitney test and logistic regression with calculation of odds ratio. Repeated event analysis was conducted using a nonlinear mixed effect model.

Results

In 237 enrolled patients [median age 40 years, 45% females], median CL was lower in patients achieving ER as compared with those with persistent active endoscopic disease [median 0.247 L/day vs 0.326 L/day, respectively] [p <0.01]. There was no significant difference in ADA concentration between patients in endoscopic remission compared with those with recurrence [median 9.3 µg/mL vs 11.7 µg/mL, respectively]. Sustained CRP-based clinical remission and FC levels below 100 µg/g were generally associated with lower CL and higher ADA concentration. Repeated event analysis confirmed those findings with better performances of CL than concentration in associating with ER and other outcomes.

Conclusion

Lower ADA clearance is associated with an improved clinical outcome for patients with Crohn’s disease and may be a superior pharmacokinetic measure than concentration.
Combining cardiopulmonary exercise testing with echocardiography: a multiparametric approach to the cardiovascular and cardiopulmonary systems
Authors: Del Punta Lavinia , De Biase Nicolò , Armenia Silvia , Di Fiore Valerio , Maremmani Davide , Gargani Luna , Mazzola Matteo , De Carlo Marco , Mengozzi Alessandro , Lomonaco Tommaso , Galeotti Gian Giacomo , Dini Frank L , Masi Stefano , Pugliese Nicola Riccardo
Published: August 2023

Exercise intolerance is a prominent feature of several cardiovascular conditions. However, the physical effort requires the intertwined adaptation of several factors, namely the cardiovascular system, the lungs, and peripheral muscles. Several abnormalities in each domain may be present in a given patient. Cardiopulmonary exercise testing (CPET) has been used to investigate metabolic and ventilatory alterations responsible for exercise intolerance but does not allow for direct evaluation of cardiovascular function. However, this can readily be obtained by concomitant exercise-stress echocardiography (ESE). The combined CPET-ESE approach allows for precise and thorough phenotyping of the pathophysiologic mechanisms underpinning exercise intolerance. Thus, it can be used to refine the diagnostic workup of patients with dyspnoea of unknown origin, as well as improve risk stratification and potentially guide the therapeutic approach in specific conditions, including left and right heart failure or valvular heart disease. However, given its hitherto sporadic use, both the conceptual and technical aspects of CPET-ESE are often poorly known by the clinician. Improving knowledge in this field could significantly aid in anticipating individual disease trajectories and tailoring treatment strategies accordingly. Therefore, we designed this review to revise the pathophysiologic correlates of exercise intolerance, the practical principles of the combined CPET-ESE examination, and its main applications according to current literature.
Real Exchange Rates and the Earnings of Immigrants
Authors: Dustmann Christian , Ku Hyejin , Surovtseva Tetyana
Published: August 2023

We relate origin-destination real price differences to immigrants’ reservation wages and their career trajectories, exploiting administrative data from Germany and the 2004 enlargement of the European Union. We find that immigrants who enter Germany when a unit of earnings from Germany allows for larger consumption at home settle for lower entry wages, but subsequently catch up to those arriving with less favourable exchange rates, through transition to better-paying occupations and firms. Similar patterns hold in the United States data. Our analysis offers one explanation for the widespread phenomenon of immigrants’ downgrading, with new implications for immigrant cohort effects and assimilation profiles.
Reference genomes for BALB/c Nude and NOD/SCID mouse models
Authors: Schmid-Siegert Emanuel , Qin Mengting , Tian Huan , Arpat Bulak , Chen Bonnie , Xenarios Ioannis
Published: August 2023

Mouse xenograft models play a vital role in tumor studies for research as well as for screening of drugs for the pharmaceutical industry. In particular, models with compromised immunity are favorable to increase the success of transplantation, such as, e.g. NOD/SCID and BALB/c Nude strains. The genomic sequence and alterations of many of these models still remain elusive and might hamper a model’s further optimization or proper adapted usage. This can be in respect to treatments (e.g. NOD/SCID sensitivity to radiation), experiments or analysis of derived sequencing data of such models. Here we present the genome assemblies for the NOD/SCID and BALB/c Nude strains to overcome this short-coming for the future and improve our understanding of these models in the process. We highlight as well first insights into observed genomic differences for these models compared to the C57BL/6 reference genome. Genome assemblies for both are close to full-chromosome representations and provided with liftover annotations from the GRCm39 reference genome.
Two independent DNA repair pathways cause mutagenesis in template switching deficient Saccharomyces cerevisiae
Authors: Jiang Yangyang Kate , Medley Eleanor A , Brown Grant W
Published: August 2023

Upon DNA replication stress, cells utilize the postreplication repair pathway to repair single-stranded DNA and maintain genome integrity. Postreplication repair is divided into 2 branches: error-prone translesion synthesis, signaled by proliferating cell nuclear antigen (PCNA) monoubiquitination, and error-free template switching, signaled by PCNA polyubiquitination. In Saccharomyces cerevisiae, Rad5 is involved in both branches of repair during DNA replication stress. When the PCNA polyubiquitination function of Rad5 s disrupted, Rad5 recruits translesion synthesis polymerases to stalled replication forks, resulting in mutagenic repair. Details of how mutagenic repair is carried out, as well as the relationship between Rad5-mediated mutagenic repair and the canonical PCNA-mediated mutagenic repair, remain to be understood. We find that Rad5-mediated mutagenic repair requires the translesion synthesis polymerase ζ but does not require other yeast translesion polymerase activities. Furthermore, we show that Rad5-mediated mutagenic repair is independent of PCNA binding by Rev1 and so is separable from canonical mutagenic repair. In the absence of error-free template switching, both modes of mutagenic repair contribute additively to replication stress response in a replication timing-independent manner. Cellular contexts where error-free template switching is compromised are not simply laboratory phenomena, as we find that a natural variant in RAD5 is defective in PCNA polyubiquitination and therefore defective in error-free repair, resulting in Rad5- and PCNA-mediated mutagenic repair. Our results highlight the importance of Rad5 in regulating spontaneous mutagenesis and genetic diversity in S. cerevisiae through different modes of postreplication repair.
Autophagy impairment and lifespan reduction caused by Atg1 RNAi or Atg18 RNAi expression in adult fruit flies (Drosophila melanogaster)
Authors: Bierlein Mariah , Charles Joseph , Polisuk-Balfour Trevor , Bretscher Heidi , Rice Micaela , Zvonar Jacklyn , Pohl Drake , Winslow Lindsey , Wasie Brennah , Deurloo Sara , Van Wert Jordan , Williams Britney , Ankney Gabrielle , Harmon Zachary , Dann Erica , Azuz Anna , Guzman-Vargas Alex , Kuhns Elizabeth , Neufeld Thomas P , O’Connor Michael B , Amissah Felix , Zhu Changqi C
Published: August 2023

Autophagy, an autophagosome and lysosome-based eukaryotic cellular degradation system, has previously been implicated in lifespan regulation in different animal models. In this report, we show that expression of the RNAi transgenes targeting the transcripts of the key autophagy genes Atg1 or Atg18 in adult fly muscle or glia does not affect the overall levels of autophagosomes in those tissues and does not change the lifespan of the tested flies but the lifespan reduction phenotype has become apparent when Atg1 RNAi or Atg18 RNAi is expressed ubiquitously in adult flies or after autophagy is eradicated through the knockdown of Atg1 or Atg18 in adult fly adipocytes. Lifespan reduction was also observed when Atg1 or Atg18 was knocked down in adult fly enteroblasts and midgut stem cells. Overexpression of wild-type Atg1 in adult fly muscle or adipocytes reduces the lifespan and causes accumulation of high levels of ubiquitinated protein aggregates in muscles. Our research data have highlighted the important functions of the key autophagy genes in adult fly adipocytes, enteroblasts, and midgut stem cells and their undetermined roles in adult fly muscle and glia for lifespan regulation.
Biochemical characterization of a new ulvan lyase and its applicability in utilization of ulvan and preparation of ulva oligosaccharides
Authors: Li Chen , Tang Tiancheng , Jiang Jinju , Yao Zhong , Zhu Benwei
Published: August 2023

Ulva is globally distributed specie and has a high economic value. Ulvan is one of the main active substances in Ulva, which has a variety of biological properties. Ulvan lyase degrades ulvan through a β-elimination mechanism which cleaves the β-glycosidic bond between Rha3S and GlcA or IdoA. The complex monosaccharide composition of ulvan makes it promising for use in food and pharmaceutical applications. This thesis explores a putative ulvan lyase from Alteromonas sp. KUL_42. We expressed and purified the protein, performed a series of characterizations and signal peptide had been removed. The results showed that the protein molecular weight of ULA-2 was 53.97 kDa, and it had the highest catalytic activity at 45 °C and pH 8.0 in Tris–HCl buffer. The Km and Vmax values were 2.24 mg · mL−1 and 2.048 μmol · min−1 · mL−1, respectively. The activity of ULA-2 was able to maintain more than 80% at 20 ~ 30 °C. ESI-MS analysis showed that the primary end-products were mainly disaccharides to tetrasaccharides. The study of ULA-2 enriches the ulvan lyase library, promotes the development and high-value utilization of Ulva resources, and facilitates further research applications of ulvan lyase in ulva oligosaccharides.
Cytokine signaling in chimeric antigen receptor T-cell therapy
Authors: Kagoya Yuki
Published: August 2023

Adoptive immunotherapy using chimeric antigen-receptor (CAR)-engineered T cells can induce robust antitumor responses against hematologic malignancies. However, its efficacy is not durable in the majority of the patients, warranting further improvement of T-cell functions. Cytokine signaling is one of the key cascades regulating T-cell survival and effector functions. In addition to cytokines that use the common γ chain as a receptor subunit, multiple cytokines regulate T-cell functions directly or indirectly. Modulating cytokine signaling in CAR-T cells by genetic engineering is one promising strategy to augment their therapeutic efficacy. These strategies include ectopic expression of cytokines, cytokine receptors, and synthetic molecules that mimic endogenous cytokine signaling. Alternatively, autocrine IL-2 signaling can be augmented through reprogramming of CAR-T cell properties through transcriptional and epigenetic modification. On the other hand, cytokine production by CAR-T cells triggers systemic inflammatory responses, which mainly manifest as adverse events such as cytokine-release syndrome (CRS) and neurotoxicity. In addition to inhibiting direct inflammatory mediators such as IL-6 and IL-1 released from activated macrophages, suppression of T-cell-derived cytokines associated with the priming of macrophages can be accomplished through genetic modification of CAR-T cells. In this review, I will outline recently developed synthetic biology approaches to exploit cytokine signaling to enhance CAR-T cell functions. I will also discuss therapeutic target molecules to prevent or alleviate CAR-T cell-related toxicities.
Embedding research study recruitment within the patient portal preCheck-in
Authors: Leuchter Richard K , Ma Suzette , Bell Douglas S , Hays Ron D , Vidorreta Fernando Javier Sanz , Binder Sandra L , Sarkisian Catherine A
Published: August 2023

Objective

Patient portals are increasingly used to recruit patients in research studies, but communication response rates remain low without tactics such as financial incentives or manual outreach. We evaluated a new method of study enrollment by embedding a study information sheet and HIPAA authorization form (HAF) into the patient portal preCheck-in (where patients report basic information like allergies).

Materials and Methods

Eligible patients who enrolled received an after-visit patient-reported outcomes survey through the patient portal. No additional recruitment/messaging efforts were made.

Results

A total of 386 of 843 patients completed preCheck-in, 308 of whom signed the HAF and enrolled in the study (37% enrollment rate). Of 93 patients who were eligible to receive the after-visit survey, 45 completed it (48% completion rate).

Conclusion

Enrollment and survey completion rates were higher than what is typically seen with recruitment by patient portal messaging, suggesting that preCheck-in recruitment can enhance research study recruitment and warrants further investigation.
Treating Delinquent and Feebleminded Juveniles at the Beloit Industrial School for Girls in Early Twentieth-Century Kansas
Authors: McCrea Heather L
Published: August 2023

This study explores the troubling and unintended consequences of public health efforts to address the problem of juvenile delinquency and feeblemindedness. Health care professionals, superintendents, and other authority figures equated undesirable juvenile behaviors such as keeping “bad company” or “falling in with the wrong crowd,” truancy, and petty theft with poor breeding, low intelligence, and inheritable criminal tendencies. This article interrogates historical documentation culled from the Kansas State Historical Society (KSHS) and focuses on a few specific cases to reveal the ways a patriarchal political and medical state system both protected and alienated young woman accused of a myriad of behavior issues including delinquency, incorrigibility, and feeblemindedness. I highlight the lives of juvenile women sentenced to the Beloit Industrial School for Girls not simply to better understand an isolated period in United States history but also reproduction. The broader implications of the narratives of girls housed at the Beloit Industrial School for Girls throughout the first half of the twentieth century in Kansas reveal troubling and unintended consequences of public health efforts to fix the problems of delinquency, contagion, and the generational inheritance of undesirable characteristics.