bluuebunny/crossref_metadata_2025 huggingface dataset:
An Electrochemical Aptasensor Integrating Zeolitic Imidazolate Framework for Highly Selective Detection of Bioaerosols
Authors: Wang Pu , Zhang Rui , Wu Yunping , Chang Yangyang , Liu Meng
Published: September 2022

Bioaerosols are the biological materials in the air, which may cause a continuous threat to human health. However, there are many challenges in monitoring bioaerosols such as lack of sensitivity and selectivity. Herein, we synthesized a series of nanohybrids containing zeolitic imidazolate frameworks (ZIFs) and covalent organic frameworks (COFs) to construct an electrochemical aptasensor for detecting adenosine triphosphate (ATP), a biomarker for bioaerosols. The synthesized nanohybrids can not only improve the selectivity of aptasensor because of the original crystal and chemical features of ZIF-67, but also boost its sensitivity due to the excellent conductivity of COFs. After optimizing the nanohybrids, the novel developed sensing platform achieved highly selective detection of ATP with an excellent detection limit of 0.11 nM in a wide linear range from 0.1 nM to 100 nM. Furthermore, this assay was applied to detect bioaerosols in real air samples, and the result showed a positive correlation with that of the culturing-based method, suggesting its potential applicability.
The Effects of Different Antigen–Antibody Pairs on the Results of 20 Min ELISA and 8 Min Chromatographic Paper Test for Quantitative Detection of Acetamiprid in Vegetables
Authors: Wu Yuxiang , Guo Yemin , Yang Qingqing , Li Falan , Sun Xia
Published: September 2022

To establish rapid, high-sensitive, quantitative detection of ACP residues in vegetables. A 1G2 cell clone was selected as the most sensitive for anti-ACP antibody production following secondary immunization, cell fusion, and screening. The affinity of the 1G2 antibody to each of the four coating agents (imidacloprid–bovine serum albumin [BSA], thiacloprid–BSA, imidaclothiz–BSA, and ACP-BSA) was determined using a 20 min enzyme-linked immunosorbent assay (ELISA). The half maximal inhibitory concentration (IC50) was 0.51–0.62 ng/mL, showing no significant difference in affinity to different antigens. However, we obtained IC50 values of 0.58 and 1.40 ng/mL on the linear regression lines for 1G2 anti-ACP antibody/imidacloprid–BSA and 1G2 anti-ACP antibody/thiacloprid–BSA, respectively, via quantum dot (QD)-based immunochromatography. That is, the 1G2 antibody/imidacloprid–BSA pair (the best combination) was about three times more sensitive than the 1G2 antibody/thiacloprid–BSA pair in immunochromatographic detection. The best combination was used for the development of an 8 min chromatographic paper test. With simple and convenient sample pretreatment, we achieved an average recovery of 75–117%. The coefficient of variation (CoV) was <25% for all concentrations tested, the false–positive rate was <5%, the false–negative rate was 0%, and the linear range of the method was 50–1800 μg/kg. These performance metrics met the ACP detection standards in China, the European Union (EU), and the United States (US). In summary, in this study, we established an 8 min QD-based immunochromatographic stripe for the rapid and accurate quantitative determination of ACP residues in vegetables.
Carbon Nanotube and Its Derived Nanomaterials Based High Performance Biosensing Platform
Authors: Mondal Jagannath , An Jeong Man , Surwase Sachin S. , Chakraborty Kushal , Sutradhar Sabuj Chandra , Hwang Joon , Lee Jaewook , Lee Yong-Kyu
Published: September 2022

After the COVID-19 pandemic, the development of an accurate diagnosis and monitoring of diseases became a more important issue. In order to fabricate high-performance and sensitive biosensors, many researchers and scientists have used many kinds of nanomaterials such as metal nanoparticles (NPs), metal oxide NPs, quantum dots (QDs), and carbon nanomaterials including graphene and carbon nanotubes (CNTs). Among them, CNTs have been considered important biosensing channel candidates due to their excellent physical properties such as high electrical conductivity, strong mechanical properties, plasmonic properties, and so on. Thus, in this review, CNT-based biosensing systems are introduced and various sensing approaches such as electrochemical, optical, and electrical methods are reported. Moreover, such biosensing platforms showed excellent sensitivity and high selectivity against not only viruses but also virus DNA structures. So, based on the amazing potential of CNTs-based biosensing systems, healthcare and public health can be significantly improved.
Global and Regional Structural Differences and Prediction of Autistic Traits during Adolescence
Authors: Nees Frauke , Banaschewski Tobias , Bokde Arun L. W. , Desrivières Sylvane , Grigis Antoine , Garavan Hugh , Gowland Penny , Grimmer Yvonne , Heinz Andreas , Brühl Rüdiger , Isensee Corinna , Becker Andreas , Martinot Jean-Luc , Paillère Martinot Marie-Laure , Artiges Eric , Papadopoulos Orfanos Dimitri , Lemaître Hervé , Stringaris Argyris , van Noort Betteke , Paus Tomáš , Penttilä Jani , Millenet Sabina , Fröhner Juliane H. , Smolka Michael N. , Walter Henrik , Whelan Robert , Schumann Gunter , Poustka Luise ,   on behalf of the IMAGEN Consortium
Published: September 2022

Background: Autistic traits are commonly viewed as dimensional in nature, and as continuously distributed in the general population. In this respect, the identification of predictive values of markers such as subtle autism-related alterations in brain morphology for parameter values of autistic traits could increase our understanding of this dimensional occasion. However, currently, very little is known about how these traits correspond to alterations in brain morphology in typically developing individuals, particularly during a time period where changes due to brain development processes do not provide a bias. Therefore, in the present study, we analyzed brain volume, cortical thickness (CT) and surface area (SA) in a cohort of 14–15-year-old adolescents (N = 285, female: N = 162) and tested their predictive value for autistic traits, assessed with the social responsiveness scale (SRS) two years later at the age of 16–17 years, using a regression-based approach. We found that autistic traits were significantly predicted by volumetric changes in the amygdala (r = 0.181), cerebellum (r = 0.128) and hippocampus (r = −0.181, r = −0.203), both in boys and girls. Moreover, the CT of the superior frontal region was negatively correlated (r = −0.144) with SRS scores. Furthermore, we observed a significant association between the SRS total score and smaller left putamen volume, specifically in boys (r = −0.217), but not in girls. Our findings suggest that neural correlates of autistic traits also seem to lie on a continuum in the general population, are determined by limbic–striatal neuroanatomical brain areas, and are partly dependent on sex. As we imaged adolescents from a large population-based cohort within a small age range, these data may help to increase the understanding of autistic-like occasions in otherwise typically developing individuals.
Association between ABCB1 rs2235048 Polymorphism and THC Pharmacokinetics and Subjective Effects following Smoked Cannabis in Young Adults
Authors: Matheson Justin , Zhang Yollanda J. , Brands Bruna , Wickens Christine M. , Tiwari Arun K. , Zai Clement C. , Kennedy James L. , Le Foll Bernard
Published: September 2022

Genetic influences on acute responses to psychoactive drugs may contribute to individual variability in addiction risk. ABCB1 is a human gene that encodes P-glycoprotein, an ATP-dependent efflux pump that may influence the pharmacokinetics of delta-9-tetrahydrocannabinol (THC), the primary psychoactive component of cannabis. Using data from 48 young adults (aged 19–25 years) reporting 1–4 days of cannabis use per week who completed a placebo-controlled human laboratory experiment, we tested the hypothesis that the rs2235048 polymorphism of ABCB1 would influence acute responses to smoked cannabis. C-allele carriers reported on average greater frequency of weekly cannabis use compared to the TT genotype carriers (TC/CC mean ± SEM = 2.74 ± 0.14, TT = 1.85 ± 0.24, p = 0.004). After smoking a single cannabis cigarette to their desired high, C-allele carriers had higher area-under-the-curve (AUC) of both THC metabolites (11-OH-THC TC/CC = 7.18 ± 9.64, TT = 3.28 ± 3.40, p = 0.05; THC-COOH TC/CC = 95.21 ± 116.12, TT = 45.92 ± 42.38, p = 0.043), and these results were impact by self-reported ethnicity. There were no significant differences in self-reported subjective drug effects except for a greater AUC of visual analogue scale rating of drug liking (TC/CC = 35,398.33 ± 37,233.72, TT = 15,895.56 ± 13,200.68, p = 0.017). Our preliminary findings suggest that further work in a larger sample should investigate whether human ABCB1 influences cannabis-related phenotypes and plays a role in the risk of developing a cannabis use disorder.
Applying the Properties of Neurons in Machine Learning: A Brain-like Neural Model with Interactive Stimulation for Data Classification
Authors: Li Da , Li Molan , Huang Zhili
Published: September 2022

Some neural models achieve outstanding results in image recognition, semantic segmentation and natural language processing. However, their classification performance on structured and small-scale datasets that do not involve feature extraction is worse than that of traditional algorithms, although they require more time to train. In this paper, we propose a brain-like neural model with interactive stimulation (NMIS) that focuses on data classification. It consists of a primary neural field and a senior neural field that play different cognitive roles. The former is used to correspond to real instances in the feature space, and the latter stores the category pattern. Neurons in the primary field exchange information through interactive stimulation and their activation is transmitted to the senior field via inter-field interaction, simulating the mechanisms of neuronal interaction and synaptic plasticity, respectively. The proposed NMIS is biologically plausible and does not involve complex optimization processes. Therefore, it exhibits better learning ability on small-scale and structured datasets than traditional BP neural networks. For large-scale data classification, a nearest neighbor NMIS (NN_NMIS), an optimized version of NMIS, is proposed to improve computational efficiency. Numerical experiments performed on some UCI datasets show that the proposed NMIS and NN_NMIS are significantly superior to some classification algorithms that are widely used in machine learning.
A Combined Image- and Coordinate-Based Meta-Analysis of Whole-Brain Voxel-Based Morphometry Studies Investigating Subjective Tinnitus
Authors: Makani Punitkumar , Thioux Marc , Pyott Sonja J. , van Dijk Pim
Published: September 2022

Previous voxel-based morphometry (VBM) studies investigating tinnitus have reported structural differences in a variety of spatially distinct gray matter regions. However, the results have been highly inconsistent and sometimes contradictory. In the current study, we conducted a combined image- and coordinate-based meta-analysis of VBM studies investigating tinnitus to identify robust gray matter differences associated with tinnitus, as well as examine the possible effects of hearing loss on the outcome of the meta-analysis. The PubMed and Web of Science databases were searched for studies published up to August 2021. Additional manual searches were conducted for studies published up to December 2021. A whole-brain meta-analysis was performed using Seed-Based d Mapping with Permutation of Subject Images (SDM-PSI). Fifteen studies comprising 423 individuals with tinnitus and either normal hearing or hearing loss (mean age 50.94 years; 173 females) and 508 individuals without tinnitus and either normal hearing or hearing loss (mean age 51.59 years; 234 females) met the inclusion criteria. We found a small but significant reduction in gray matter in the left inferior temporal gyrus for groups of normal hearing individuals with tinnitus compared to groups of hearing-matched individuals without tinnitus. In sharp contrast, in groups with hearing loss, tinnitus was associated with increased gray matter levels in the bilateral lingual gyrus and the bilateral precuneus. Those results were dependent upon matching the hearing levels between the groups with or without tinnitus. The current investigation suggests that hearing loss is the driving force of changes in cortical gray matter across individuals with and without tinnitus. Future studies should carefully account for confounders, including hearing loss, hyperacusis, anxiety, and depression, to identify gray matter changes specifically related to tinnitus. Ultimately, the aggregation of standardized individual datasets with both anatomical and useful phenotypical information will permit a better understanding of tinnitus-related gray matter differences, the effects of potential comorbidities, and their interactions with tinnitus.
Investigating the Effect of Compassion Fade in Volunteer Tourism
Authors: Lee Sae-Mi
Published: September 2022

This study investigated the relationship between the type of volunteer tourism (human vs. flora vs. fauna) and the type of message (individual with no statistic vs. individual with small statistic vs. individual with large statistic) and potential tourists’ attitudes towards volunteer tourism and their intention to donate their time. To do so, this study conducted a between-subject 3 × 3 factorial design online experiment, where the influences of compassion fade on attitudes and behavioral intention to donate time for volunteer tourism, along with the impacts of positive affect, emotional involvement, and credibility, were examined. The results of the current study revealed that type of volunteer tourism and type of message do not affect attitude towards volunteer tourism and attitude towards the ad. Further analysis indicated that, among all three mediating variables, only positive affect mediated the relationship between type of volunteer tourism and attitude towards volunteer tourism, and all other hypotheses were not statistically significant. Moreover, the results indicated that there is a positive relationship between perceived ad credibility and attitude towards the ad, and also between perceived ad credibility and attitude towards volunteer tourism. The implications of these results are discussed based on the empirical findings.
Development of a Prediction Model of the Pedestrian Mean Velocity Based on LES of Random Building Arrays
Authors: Zaki Sheikh Ahmad , Shuhaimi Saidatul Sharin , Mohammad Ahmad Faiz , Ali Mohamed Sukri Mat , Jamaludin Khairur Rijal , Ahmad Mardiana Idayu
Published: September 2022

Wind speed in urban areas is influenced by the interaction between wind flow and building geometry; at the pedestrian level, the interaction is more complex, particularly with high building density. This study investigated the wind velocity distribution and the mean velocity ratio at the pedestrian level using the large-eddy simulation (LES) database based on random building arrays of several plan area densities, λp. The heights of random buildings are between 0.36 h and 3.76 h where h = 0.025 m. Mean streamwise velocity profiles were obtained at the pedestrian level for all arrays and were found to decrease as λp increased. Wind flow patterns at the pedestrian level were highly influenced by adjacent buildings, especially in denser conditions, λp > 0.17. The pedestrian-level mean velocity was obtained around each building, and the relationship between the local mean velocity ratio, Vp(t) and the local frontal area density, λf(t) was analyzed. Subsequently, a prediction model was formulated based on the building’s aspect ratio, αp; the correlation for high-rise buildings with 2.64 h ≤ αp ≤ 3.76 h was high at 0.8, while a lower correlation was obtained for lower buildings due to random positioning and surrounding geometric effects. Therefore, the impact of high-rise buildings on pedestrian wind velocity can be estimated more accurately using the formulated model.
Evaluation of the Low-Temperature Cracking Performance of Recycled Asphalt Mixture: A Development of Equivalent Fracture Temperature
Authors: Yang Tao , Jia Yanshun , Pan Yuanyuan , Zhao Yongli
Published: September 2022

This study aims to develop a new index to evaluate the low-temperature cracking performance (LTCP) of recycled asphalt mixtures. To achieve this, the assumption that fracture energy has limitation in evaluating the LTCP of mixtures was put forward firstly. To reveal this limitation theoretically, a concept of energy absorption rate that characterized the fracture energy of the mixtures was then given. Thirdly, an equivalent fracture temperature (EFT) corresponding to the critical cracking temperature in a thermal stress restrained specimen test (TSRST) was proposed to evaluate the LTCP of mixtures based on a three-point bending beam (3PBB) test. Finally, some data derived from previous work were collected to verify the proposed assumption, and the 3PBB test and TSRST were conducted to investigate the LTCP of five recycled mixtures with different reclaimed asphalt pavement (RAP) material contents and to verify the rationality of the proposed EFT. The results confirmed that fracture energy had some limitations in predicting the LTCP of mixtures. The EFT was as accurate as the critical cracking temperature in evaluating the LTCP of mixtures. Compared to fracture energy and critical cracking temperature, EFT had bigger absolute change and relative change between different mixtures, meaning it was better to differentiate the LTCP of mixtures. Compared to failure strain, EFT was also more definite and less variable when processed by different data analysts, meaning it was more objective.
Flexural Test and Numerical Simulation of a New Combination Splice for Prestressed, Precast Concrete Piles Using High-Strength Steel Strands
Authors: Chen Kepeng , Gan Gang
Published: September 2022

Prestressed, precast concrete piles using High-Strength Steel Strands (PPCPs using HSSS) are a new type of precast pile. Compared with prestressed high-strength concrete (PHC) piles, the adoption of ultra-high-strength concrete and HSSS not only improves the load-bearing capacity, but also enhances the ductility of precast piles. The engineering application of PPCPs using HSSS requires not only a high bearing capacity of the pile segments, but also reliable splicing to ensure cooperation between pile segments. Based on the characteristics of strand anchorage plates, this paper proposes a new combination splice using the clamp ring and welding (Combination Splice). The theoretical analysis and design method of this Combination Splice is introduced. This research gives a thorough investigation into the flexural performance of PPCPs using HSSS with the Combination Splice. The flexural tests of PPCPs using HSSS with the Combination Splice were firstly conducted on eight full-scale pile specimens with three different pile diameters and four different steel reinforcement ratios. The flexural performances are evaluated in terms of crack resistance, flexural capacities, crack distribution, as well as strain development. The results indicate that the Combination Splice remain safe and intact when the piles reach the ultimate bending capacity. The ultimate bending moment of tested specimens with the Combination Splice is, on average, 10% larger than that of specimens using a theoretical formula. In light of the experimental data, a finite element analysis (FEA) model has been created to simulate the flexural performance of the piles with the Combination Splice. The FEA results show that the load–displacement curves and crack distribution regions are in good agreement with the experimental findings, which verifies the reliability and accuracy of the FEA model. The parameter analysis investigates the effects of the assembly gap and clamp ring corrosion on the flexural performance of PPCPs using HSSS. The results show that assembly gaps have a greater influence on the flexural capacity and deformation, while the influence of the clamp ring corrosion is negligible, indicating that the Combination Splice has certain advantages in terms of durability.
Degradation of Reinforced Concrete Beams Subjected to Sustained Loading and Multi-Environmental Factors
Authors: Li Shengyuan , Lv Henglin , Huang Tianhua , Zhang Zhigang , Yao Jin , Ni Xin
Published: September 2022

In the process of service, reinforced concrete structures have to bear both load and multi-environmental factors. The deterioration of reinforced concrete beams is critical to the durability, safety, and sustainability of reinforced concrete structures. The main aim of the present research is to determine the degradation mechanism of reinforced concrete beams subjected to sustained loading and multi-environmental factors. Reinforced concrete beam specimens were prepared, loaded and then exerted multi-environmental factors. At the end of each degradation period, the degradation of concrete (chemical contents of concrete beam surfaces, carbonation depth, compressive strength and maximum cracks) and the corrosion of steel bars (corrosion ratio and tensile strength) were continuously measured. Moreover, degraded reinforced concrete beams were flexural loaded in four-point bending failure tests. The degradation mechanism of reinforced concrete beams subjected to sustained loading and multi-environmental factors was analyzed. Thus, this study can promote a comprehensive understanding of reinforced concrete beams subjected to sustained loading and multi-environmental factors.
Presentation and Elaboration of the Folk Intangible Cultural Heritage from the Perspective of the Landscape
Authors: Zhuang Qianda , Wan Mengying , Zheng Guoquan
Published: September 2022

The folklore of intangible cultural heritage (FICH) is mainly expressed in folkloric activities, which include traditional festivals, living customs, production practices, folk beliefs, life rituals and folk costumes. The more reasonable and efficient ways to achieve conservation and transmission of FICH have become an urgent problem to be solved. Landscape presentation offers a potential method to address that by excavating the landscape characteristics of FICH based on its in-depth connotation and development history. This study aims to explore the cultural connotation of the FICH and extract the elements of landscape design, thus presenting and expressing the FICH using landscape as a carrier, to achieve the conservation and inheritance of the FICH. This research took the Taishun Hundred-family Feast culture, one of FICH in Sankui Town, Taishun County, China, as the study case, and extracted the landscape design elements in FICH after its content excavation and conducted presentation with cultural objectification, landscape narrative and contextualization. The results showed that the Hundred-family Feast culture contains rich landscape genes which can be divided into the ritual culture, food culture, festival culture and spiritual culture. Some of the elements in the Hundred-family Feast culture in terms of patterns, forms and colours for the content of activities, material carriers and spiritual places were also extracted for the landscape presentation. According to the different types and places of the Hundred-family Feast culture activities, the centre of Sankui Town is divided into four landscape thematic areas, namely the Hundred-family Feast cultural entrance experience zone, the food culture experience zone, ritual culture experience zone, and activity performance experience zone. The landscape element and spatial carriers were designed and illustrated for conserving and recovering the Hundred-family Feast culture, respectively. This study innovatively analyses the FICH from the perspective of the characteristics and constituent elements of the landscape and establishes a more reasonable framework system for the method of landscape presentation of the FICH in a structured and comprehensive manner. It enriches the theoretical system of intangible cultural heritage protection and its inheritance via landscape presentation methods for folklore activities.
Experimental-Numerical Analysis of the Effect of Bar Diameter on Bond in Pull-Out Test
Authors: Burdziński Marcin , Niedostatkiewicz Maciej
Published: September 2022

Bar diameter is one of the basic factors affecting bond behavior, which is still of interest due to opposing opinions regarding its effect on bond behavior in the pull-out test. This paper presents an experimental and numerical bond analysis of ribbed reinforcing bar in concrete. The aim was to experimentally evaluate the effect of bar diameter on the bond behavior in the pull-out test and to perform numerical simulations of the conducted experiments in ABAQUS to verify their convergence to the obtained experimental results. The experiments used concrete of C35/45 grade and B500SP reinforcing steel bars of three diameters: 10, 12, and 16 mm. FEA simulations employed the Concrete Damaged Plasticity (CDP) material model and the Contact Cohesive Behavior (CCB) method to model the concrete–bar interface. The study shows that bar diameter significantly affects the bond, both on the bond stress–slip relationship and the type of bond failure, as well as on the bond strength. FEA simulations correctly reflected the bond behavior observed in the specimens. The analytical models presented estimates that were too conservative regarding the maximum bond stress relative to the experimental results.
Novel Selenoesters as a Potential Tool in Triple-Negative Breast Cancer Treatment
Authors: Radomska Dominika , Czarnomysy Robert , Szymanowska Anna , Radomski Dominik , Domínguez-Álvarez Enrique , Bielawska Anna , Bielawski Krzysztof
Published: September 2022

Disturbing cancer statistics, especially for breast cancer, are becoming a rationale for the development of new anticancer therapies. For the past several years, studies have been proving a greater role of selenium in the chemoprevention of many cancers than previously considered; hence, a trend to develop compounds containing this element as potential agents with anticancer activity has been set for some time. Therefore, our study aimed to evaluate the anticancer activity of novel selenoesters (EDA-71, E-NS-4) in MCF-7 and MDA-MB-231 human breast cancer cells. The assays evaluating proliferation and cell viability, and flow cytometer analysis of apoptosis/autophagy induction, changes in mitochondrial membrane potential, disruption of cell cycle phases, and protein activity of mTOR, NF-κB, cyclin E1/A2, and caspases 3/7, 8, 9, 10 were performed. The obtained results indicate that the tested selenoesters are highly cytotoxic and exhibit antiproliferative activity at low micromolar doses (<5 µM) compared with cisplatin. The most active compound—EDA-71—highly induces apoptosis, which proceeds via both pathways, as evidenced by the activation of all tested caspases. Furthermore, we observed the occurrence of autophagy (↓ mTOR levels) and cell cycle arrest in the S or G2/M phase (↓ cyclin E1, ↑ cyclin A2).
Exercise Promotes Pro-Apoptotic Ceramide Signaling in a Mouse Melanoma Model
Authors: Lee Jonghae , Savage Hannah , Maegawa Shinji , Ballarò Riccardo , Pareek Sumedha , Guerrouahen Bella Samia , Gopalakrishnan Vidya , Schadler Keri
Published: September 2022

Ceramides are essential sphingolipids that mediate cell death and survival. Low ceramide content in melanoma is one mechanism of drug resistance. Thus, increasing the ceramide content in tumor cells is likely to increase their sensitivity to cytotoxic therapy. Aerobic exercise has been shown to modulate ceramide metabolism in healthy tissue, but the relationship between exercise and ceramide in tumors has not been evaluated. Here, we demonstrate that aerobic exercise causes tumor cell apoptosis and accumulation of pro-apoptotic ceramides in B16F10 but not BP melanoma models using mice. B16F10 tumor-bearing mice were treated with two weeks of moderate treadmill exercise, or were control, unexercised mice. A reverse-phase protein array was used to identify canonical p53 apoptotic signaling as a key pathway upregulated by exercise, and we demonstrate increased apoptosis in tumors from exercised mice. Consistent with this finding, pro-apoptotic C16-ceramide, and the ceramide generating enzyme ceramide synthase 6 (CerS6), were higher in B16F10 tumors from exercised mice, while pro-survival sphingosine kinase 1 (Sphk1) was lower. These data suggest that exercise contributes to B16F10 tumor cell death, possibly by modulating ceramide metabolism toward a pro-apoptotic ceramide/sphingosine-1-phosphate balance. However, these results are not consistent in BP tumors, demonstrating that exercise can have different effects on tumors of different patient or mouse origin with the same diagnosis. This work indicates that exercise might be most effective as a therapeutic adjuvant with therapies that kill tumor cells in a ceramide-dependent manner.
Single-Cell Profiling of the Immune Atlas of Tumor-Infiltrating Lymphocytes in Endometrial Carcinoma
Authors: Jiang Fang , Jiao Yuhao , Yang Kun , Mao Mingyi , Yu Mei , Cao Dongyan , Xiang Yang
Published: September 2022

Endometrial carcinoma (EC) is a gynecological malignancy with a high incidence; however, thorough studies on tumor-infiltrating lymphocyte (TIL) populations in EC are lacking. We aimed to map the immune atlas of TILs in type I EC via single-cell RNA sequencing (scRNA-seq), mass cytometry and flow cytometry analysis. We found that natural killer (NK) cells and CD8+ T lymphocytes were the major components of TILs in EC patients. We first identified three transcriptionally distinct NK cell subsets, which are likely to possess diverse anti-tumor functions. Additionally, CD103+ cells substantially contributed to the CD8+ T cell population. The signature gene expression of CD103+ CD8+ T cells indicated the tissue residency, immunological memory, and exhaustion properties of this cell subset, which were defined as tissue-resident memory T cells (TRM cells). Moreover, based on scRNA-seq and mass cytometry analysis, we first identified the intrinsic heterogeneity of CD103+ CD8+ T cells that were thought to have a distinct cytotoxicity, cell adhesion and exhaustion status functions. Collectively, distinct subsets of NK cells were found and might shed light on future investigations. CD103+ CD8+ T cell population may be an important immunotherapeutic target in EC and targeting this cell population with combined immunosuppressive therapy might improve the efficacy of immunotherapy for EC.
IRF4 as an Oncogenic Master Transcription Factor
Authors: Wong Regina Wan Ju , Ong Jolynn Zu Lin , Theardy Madelaine Skolastika , Sanda Takaomi
Published: September 2022

IRF4 is a transcription factor in the interferon regulatory factor (IRF) family. Since the discovery of this gene, various research fields including immunology and oncology have highlighted the unique characteristics and the importance of IRF4 in several biological processes that distinguish it from other IRF family members. In normal lymphocyte development and immunity, IRF4 mediates critical immune responses via interactions with upstream signaling pathways, such as the T-cell receptor and B-cell receptor pathways, as well as their binding partners, which are uniquely expressed in each cell type. On the other hand, IRF4 acts as an oncogene in various mature lymphoid neoplasms when abnormally expressed. IRF4 induces several oncogenes, such as MYC, as well as genes that characterize each cell type by utilizing its ability as a master regulator of immunity. IRF4 and its upstream factor NF-κB form a transcriptional regulatory circuit, including feedback and feedforward loops, to maintain the oncogenic transcriptional program in malignant lymphoid cells. In this review article, we provide an overview of the molecular functions of IRF4 in mature lymphoid neoplasms and highlight its upstream and downstream pathways, as well as the regulatory circuits mediated by IRF4.
Prognostic Factors in Patients Treated with Pembrolizumab as a Second-Line Treatment for Advanced Biliary Tract Cancer
Authors: Park Chan Su , Sung Min Je , Kim So Jeong , Jo Jung Hyun , Lee Hee Seung , Chung Moon Jae , Bang Seungmin , Park Seung Woo , Song Si Young , Park Jeong Youp
Published: September 2022

Some BTC types respond to pembrolizumab, but there are no known prognostic factors to predict its treatment benefits. In this study, we attempted to identify the prognostic factors associated with pembrolizumab as a second-line treatment for gemcitabine-refractory BTC. This retrospective and single tertiary-center study involved all the consecutive patients (n = 80) with refractory advanced BTC, who were diagnosed as programmed cell death ligand 1-positive and treated with pembrolizumab between August 2017 and February 2021. The overall survival (OS) was analyzed using Cox regression analysis. The median OS was 6.0 months [95% confidence interval (CI): 3.87–8.20]; median progression-free survival was 1.9 months (95% CI: 1.82–1.98); and the response rate was 15.9%. In the multivariate Cox regression analysis, the TB [adjusted hazard ratio (HR) = 2.286; 95% CI: 1.177–4.440; p = 0.015), albumin levels (adjusted HR = 0.392; 95% CI: 0.211–0.725; p = 0.003), ALP levels (adjusted HR = 1.938; 95% CI: 1.105–3.400; p = 0.021), and LMR (adjusted HR = 0.325; 95% CI: 0.173–0.609; p < 0.001) were identified as significant variables associated with the OS. High albumin levels and LMR and low ALP levels and TB were significantly associated with better OS in patients treated with pembrolizumab.
An Overview of Pituitary Incidentalomas: Diagnosis, Clinical Features, and Management
Authors: Tahara Shigeyuki , Hattori Yujiro , Suzuki Koji , Ishisaka Eitaro , Teramoto Shinichiro , Morita Akio
Published: September 2022

Pituitary incidentalomas are tumors or mass lesions of the pituitary gland. These are incidentally discovered during imaging studies for symptoms that are not causally related to pituitary diseases. The most common symptom that triggers an examination is headache, and the most common type of pituitary incidentalomas are pituitary neuroendocrine tumors (PitNETs) and Rathke cleft cysts. The existing treatment strategy is controversial; however, surgical resection is recommended in cases of clinically non-functioning PitNETs with optic chiasm compression. In contrast, cystic lesions, such as Rathke cleft cysts, should be followed if the patients are asymptomatic. In this case, MRI and pituitary function tests are recommended every six months to one year; if there is no change, the follow-up period should be extended. The natural history of PitNET is partially known, and the management of pituitary incidentalomas is determined by this history. However, the pathogenesis of PitNET has significantly changed with the new World Health Organization classification, and follow-up is important based on this new classification. Therefore, a high level of evidence-based research is needed to consider treatment guidelines for pituitary incidentalomas in the future.
Comparing Apparent Diffusion Coefficient and FNCLCC Grading to Improve Pretreatment Grading of Soft Tissue Sarcoma—A Translational Feasibility Study on Fusion Imaging
Authors: Hettler Madelaine , Kitz Julia , Seif Amir Hosseini Ali , Guhlich Manuel , Panahi Babak , Ernst Jennifer , Conradi Lena-Christin , Ghadimi Michael , Ströbel Philipp , Jakob Jens
Published: September 2022

Histological subtype and grading are cornerstones of treatment decisions in soft tissue sarcoma (STS). Due to intratumoral heterogeneity, pretreatment grading assessment is frequently unreliable and may be improved through functional imaging. In this pilot study, 12 patients with histologically confirmed STS were included. Preoperative functional magnetic resonance imaging was fused with a computed tomography scan of the resected specimen after collecting core needle biopsies and placing radiopaque markers at distinct tumor sites. The Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grading criteria of the biopsies and apparent diffusion coefficients (ADCs) of the biopsy sites were correlated. Concordance in grading between the specimen and at least one biopsy was achieved in 9 of 11 cases (81.8%). In 7 of 12 cases, fusion imaging was feasible without relevant contour deviation. Functional analysis revealed a tendency for high-grade regions (Grade 2/3 (G2/G3)) (median (range) ± standard deviation: 1.13 (0.78–1.70) ± 0.23 × 10−3 mm2/s) to have lower ADC values than low-grade regions (G1; 1.43 (0.64–2.03) ± 0.46 × 10−3 mm2/s). In addition, FNCLCC scoring of multiple tumor biopsies proved intratumoral heterogeneity as expected. The ADC appears to correlate with the FNCLCC grading criteria. Further studies are needed to determine whether functional imaging may supplement histopathological grading.
Investigation of the Optimal Prime Boost Spacing Regimen for a Cancer Therapeutic Vaccine Targeting Human Papillomavirus
Authors: Da Silva Diane M. , Martinez Emma A. , Bogaert Lies , Kast W. Martin
Published: September 2022

Therapeutic vaccine studies should be designed to elicit durable, high magnitude, and efficacious T cell responses, all of which can be impacted by the choice of the vaccination schedule. Here, we compare different prime-boost intervals (PBI) in a human papillomavirus (HPV) model using a HPV16E7E6 Venezuelan equine encephalitis virus replicon particle (VRP) vaccination to address the optimal boosting schedule, quality of immune response, and overall in vivo efficacy. Six different vaccine regimens were tested with each group receiving booster vaccinations at different time intervals. Analysis of T-cell responses demonstrated a significant HPV16 E7 specific CD8+ T cell response with at minimum a one-week PBI between antigen re-exposure. Significant E7-specific in vivo cytotoxicity was also observed with longer PBIs. Additionally, longer PBIs led to an enhanced memory recall response to tumor challenge, which correlated with differential expansion of T cell memory subsets. Our findings imply that when using alphavirus vector platforms as a vaccination strategy, a one-week PBI is sufficient to induce high magnitude effector T cells with potent anti-tumor activity. However, longer PBIs lead to enhanced long-term protective anti-tumor immunity. These findings have implications for therapeutic vaccine clinical trials in which shorter intervals of prime-boost regimens may lead to suboptimal durable immune responses.
Impact of Preoperative Chemotherapy Features on Patient Outcomes after Hepatectomy for Initially Unresectable Colorectal Cancer Liver Metastases: A LiverMetSurvey Analysis
Authors: Innominato Pasquale F. , Cailliez Valérie , Allard Marc-Antoine , Lopez-Ben Santiago , Ferrero Alessandro , Marques Hugo , Hubert Catherine , Giuliante Felice , Pereira Fernando , Cugat Esteban , Mirza Darius F. , Costa-Maia Jose , Serrablo Alejandro , Lapointe Real , Dopazo Cristina , Tralhao Jose , Kaiser Gernot , Chen Jinn-Shiun , Garcia-Borobia Francisco , Regimbeau Jean-Marc , Skipenko Oleg , Lin Jen-Kou , Laurent Christophe , Opocher Enrico , Goto Yuichi , Chibaudel Benoist , de Gramont Aimery , Adam René
Published: September 2022

Background: Prognostic factors have been extensively reported after resection of colorectal liver metastases (CLM); however, specific analyses of the impact of preoperative systemic anticancer therapy (PO-SACT) features on outcomes is lacking. Methods: For this real-world evidence study, we used prospectively collected data within the international surgical LiverMetSurvey database from all patients with initially-irresectable CLM. The main outcome was Overall Survival (OS) after surgery. Disease-free (DFS) and hepatic-specific relapse-free survival (HS-RFS) were secondary outcomes. PO-SACT features included duration (cumulative number of cycles), choice of the cytotoxic backbone (oxaliplatin- or irinotecan-based), fluoropyrimidine (infusional or oral) and addition or not of targeted monoclonal antibodies (anti-EGFR or anti-VEGF). Results: A total of 2793 patients in the database had received PO-SACT for initially irresectable diseases. Short (<7 or <13 cycles in 1st or 2nd line) PO-SACT duration was independently associated with longer OS (HR: 0.85 p = 0.046), DFS (HR: 0.81; p = 0.016) and HS-RFS (HR: 0.80; p = 0.05). All other PO-SACT features yielded basically comparable results. Conclusions: In this international cohort, provided that PO-SACT allowed conversion to resectability in initially irresectable CLM, surgery performed as soon as technically feasible resulted in the best outcomes. When resection was achieved, our findings indicate that the choice of PO-SACT regimen had a marginal if any, impact on outcomes.
Electrocatalytic Investigation by Improving the Charge Kinetics between Carbon Electrodes and Dopamine Using Bio-Synthesized CuO Nanoparticles
Authors: Rajendrachari Shashanka , Kudur Jayaprakash Gururaj , Pandith Anup , Karaoglanli Abdullah Cahit , Uzun Orhan
Published: September 2022

We have successfully studied the charge transfer kinetics between carbon paste electrodes and dopamine using green synthesized rectangular monoclinic CuO nanoparticles (NPs) prepared by Alchemilla vulgaris leaves with the one-pot green synthesis method. The scanning electron microscopy (SEM) results confirmed the monoclinic structure with a particle size of around 85 nm. The investigation of thermal properties was carried out by thermogravimetric (TG) and differential thermal analysis (DTA). We also studied the electrochemical response of green synthesized CuO nanoparticles to detect Dopamine (DA) using cyclic voltammetry, which was proven to be an excellent electrocatalyst for the electro-oxidation of DA. The fabricated CuO nanoparticle modified carbon paste electrode (CMCPE) depicts fantastic selectivity, robustness, and sensitivity in analyzing DA in clinical and pharmaceutical preparations. The highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) orbitals of the DA were studied using positive and negative charges at the CuO modified carbon paste electrode interface. Frontier molecular orbitals of DA are plotted to understand electron transfer reactivity at the electrode interface.
Biosynthesis of 4-hydroxybenzylideneacetone by Whole-Cell Escherichia coli
Authors: Zhu Xingmiao , Chen Pengcheng , Zheng Pu
Published: September 2022

4-Hydroxy benzylideneacetone (4-HBA) is an organic synthesis intermediate and can be used as a precursor for the synthesis of raspberry ketone. Herein, 2-deoxy-D-ribose 5-phosphate aldolase (DERA) was overexpressed in E. coli BL21 (DE3) as an attractive catalyst for enzymatic aldol reactions. The aldol reaction between 4-hydroxybenzaldehyde (4-HBD) and acetone to biosynthesize 4-HBA was catalyzed by whole-cell E. coli BL21 (DE3) (pRSF-Deoc). The yield and 4-HBA concentration were 92.8% and 111.35 mM, respectively, when using 120 mM 4-HBD and acetone as substrates. When the concentration of 4-HBD was increased to 480 mM, 376.4 mM 4-HBA was obtained by a fed-batch strategy with a yield of 78.4%, which was about a 28% improvement compared to the one-time addition strategy. E. coli BL21 (DE3) (pRSF-Deoc) cells were further immobilized with K-carrageenan, and the immobilized cells still maintained a residual activity of above 90% after 10 repeated uses. Our study provides a promising method of biosynthesizing 4-HBA.
ACTN2 Mutant Causes Proteopathy in Human iPSC-Derived Cardiomyocytes
Authors: Zech Antonia T. L. , Prondzynski Maksymilian , Singh Sonia R. , Pietsch Niels , Orthey Ellen , Alizoti Erda , Busch Josefine , Madsen Alexandra , Behrens Charlotta S. , Meyer-Jens Moritz , Mearini Giulia , Lemoine Marc D. , Krämer Elisabeth , Mosqueira Diogo , Virdi Sanamjeet , Indenbirken Daniela , Depke Maren , Salazar Manuela Gesell , Völker Uwe , Braren Ingke , Pu William T. , Eschenhagen Thomas , Hammer Elke , Schlossarek Saskia , Carrier Lucie
Published: September 2022

Genetic variants in α-actinin-2 (ACTN2) are associated with several forms of (cardio)myopathy. We previously reported a heterozygous missense (c.740C>T) ACTN2 gene variant, associated with hypertrophic cardiomyopathy, and characterized by an electro-mechanical phenotype in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Here, we created with CRISPR/Cas9 genetic tools two heterozygous functional knock-out hiPSC lines with a second wild-type (ACTN2wt) and missense ACTN2 (ACTN2mut) allele, respectively. We evaluated their impact on cardiomyocyte structure and function, using a combination of different technologies, including immunofluorescence and live cell imaging, RNA-seq, and mass spectrometry. This study showed that ACTN2mut presents a higher percentage of multinucleation, protein aggregation, hypertrophy, myofibrillar disarray, and activation of both the ubiquitin-proteasome system and the autophagy-lysosomal pathway as compared to ACTN2wt in 2D-cultured hiPSC-CMs. Furthermore, the expression of ACTN2mut was associated with a marked reduction of sarcomere-associated protein levels in 2D-cultured hiPSC-CMs and force impairment in engineered heart tissues. In conclusion, our study highlights the activation of proteolytic systems in ACTN2mut hiPSC-CMs likely to cope with ACTN2 aggregation and therefore directs towards proteopathy as an additional cellular pathology caused by this ACTN2 variant, which may contribute to human ACTN2-associated cardiomyopathies.
Actin-Related Protein 4 and Linker Histone Sustain Yeast Replicative Ageing
Authors: Mołoń Mateusz , Stępień Karolina , Kielar Patrycja , Vasileva Bela , Lozanska Bonka , Staneva Dessislava , Ivanov Penyo , Kula-Maximenko Monika , Molestak Eliza , Tchórzewski Marek , Miloshev George , Georgieva Milena
Published: September 2022

Ageing is accompanied by dramatic changes in chromatin structure organization and genome function. Two essential components of chromatin, the linker histone Hho1p and actin-related protein 4 (Arp4p), have been shown to physically interact in Saccharomyces cerevisiae cells, thus maintaining chromatin dynamics and function, as well as genome stability and cellular morphology. Disrupting this interaction has been proven to influence the stability of the yeast genome and the way cells respond to stress during chronological ageing. It has also been proven that the abrogated interaction between these two chromatin proteins elicited premature ageing phenotypes. Alterations in chromatin compaction have also been associated with replicative ageing, though the main players are not well recognized. Based on this knowledge, here, we examine how the interaction between Hho1p and Arp4p impacts the ageing of mitotically active yeast cells. For this purpose, two sets of strains were used—haploids (WT(n), arp4, hho1Δ and arp4 hho1Δ) and their heterozygous diploid counterparts (WT(2n), ARP4/arp4, HHO1/hho1Δ and ARP4 HHO1/arp4 hho1Δ)—for the performance of extensive morphological and physiological analyses during replicative ageing. These analyses included a comparative examination of the yeast cells’ chromatin structure, proliferative and reproductive potential, and resilience to stress, as well as polysome profiles and chemical composition. The results demonstrated that the haploid chromatin mutants arp4 and arp4 hho1Δ demonstrated a significant reduction in replicative and total lifespan. These findings lead to the conclusion that the importance of a healthy interaction between Arp4p and Hho1p in replicative ageing is significant. This is proof of the concomitant importance of Hho1p and Arp4p in chronological and replicative ageing.