bluuebunny/crossref_metadata_2025 huggingface dataset:
Oxidative Modification Status of Human Serum Albumin Caused by Chronic Low-Dose Radiation Exposure in Mamuju, Sulawesi, Indonesia
Authors: Yamaguchi Masaru , Tatara Yota , Nugraha Eka Djatnika , Tamakuma Yuki , Sato Yoshiaki , Miura Tomisato , Hosoda Masahiro , Yoshinaga Shinji , Syaifudin Mukh , Tokonami Shinji , Kashiwakura Ikuo
Published: December 2022

The recently discovered high-level natural background radiation area (HBRA) of Mamuju in Indonesia provides a unique opportunity to study the biological effects of chronic low-dose radiation exposure on a human population. The mean total effective dose in the HBRA was approximately 69.6 mSv y−1 (range: 47.1 to 115.2 mSv y−1), based on a re-evaluation of the individual radiation exposure dose; therefore, proteomic analyses of serum components and oxidative modification profiling of residents living in the HBRA were reconducted using liquid chromatography-tandem mass spectrometry. The analysis of the oxidative modification sequences of human serum albumin revealed significant moderate correlations between the radiation dose and the modification of 12 sequences, especially the 111th methionine, 162nd tyrosine, 356th tyrosine, and 470th methionine residues. In addition, a dose-dependent variation in 15 proteins of the serum components was detected in the serum of residents exposed to chronic low-dose radiation. These findings suggest that the alterations in the expression of specific proteins and the oxidative modification responses of serum albumin found in exposed humans may be important indicators for considering the effects of chronic low-dose radiation exposure on living organisms, implying their potential utility as biomarkers of radiation dose estimation.
Heat Conduction and Cracking of Functionally Graded Materials Using an FDEM-Based Thermo-Mechanical Coupling Model
Authors: Han Du , Fan Hongwei , Yan Chengzeng , Wang Tie , Yang Yu , Ali Sajid , Wang Gang
Published: December 2022

In this paper, the steady-state and transient heat transfer processes of functionally graded materials (FGMs) are analyzed using a coupled thermo-mechanical model in a GPU parallel multiphysics finite–discrete element software, namely MultiFracS. First, the coupled model to handle the heat transfer problem of heterogeneous materials is verified. Then, the advantages and disadvantages of FGMs and composite materials in response to thermal shock loads are compared and the results indicate that FGMs can overcome extreme environments better than composite materials. Finally, the influence of the geometric distribution characteristics of the double-edge cracks in the gradient material plate on the crack propagation is analyzed. The simulation results show that the interaction between the cracks affects the crack propagation path under the thermal load. The inclination angle and spacing of double-edge cracks greatly influence crack propagation. Specifically, a larger inclination angle and spacing can lead to a smaller crack propagation angle. The approach in this paper provides a new quantitative tool for investigating the thermal, elastic, and cracking of functionally graded materials.
The Use of Asymmetric Polynomial Profiles for Planning a Smooth Trajectory
Authors: Boryga Marek , Kołodziej Paweł , Gołacki Krzysztof
Published: December 2022

This paper presents planning of smooth trajectories using the asymmetric profiles of displacement, velocity, acceleration and jerk of described higher degree polynomials. The presented way of determination of polynomial and asymmetry coefficients as well as motion time includes the procedure at both constraints of single kinematic quantities, i.e., velocity, acceleration, jerk and introducing a few constraints simultaneously. Moreover, the paper presents a method of planning trajectories with intermediate points consisting in concatenation of the analyzed polynomials. The proposed method of trajectory planning was compared to that of using the S-curve. The results in the form of kinematic quantity courses are presented graphically. The discussed method guarantees continuity of displacement, velocity, acceleration and jerk. It can be used for planning trajectories of various technical objects (e.g., manipulators, mobile robots, CNC machine tools, optical disk drives, autonomous vehicles, etc.).
New Construction Solutions of Gear Using in Space Vehicle Control Systems
Authors: Pacana Jacek , Siwiec Dominika , Pacana Andrzej
Published: December 2022

Outer space presents construction challenges that are completely different from the terrestrial environment. They should be characterized by high resilience and indefinite durability because there is no possibility of repair during exploitation. There are drives in spacecraft control systems that are necessary to move solar panels, robotic arms, and manipulators, and also to position antennas. In these devices, they have applications where harmonic drives are characterized by high kinematic accuracy but relatively low mechanical strength. The analysis presented in this study is aimed at modifying the shape of the harmonic drive to increase its durability and reliability. In this study, the most vulnerable damage element of the harmonic drive is the flexspline. The calculation was carried out using the finite element method (FEM) in the computer program ABAQUS. A standardized shape was tested as a basic model, and several other design solutions were proposed. For each of them, the mechanical strength was determined, which allowed the selection of the most preferred shape for the flexspline of the harmonic drive. The specific environmental requirements of the expectations for sand for gear used in spacecraft control systems were included in the analysis. The selected construction solutions of the flexspline allow for longer work and transfer of greater loads by the harmonic driver than the solutions currently used. The choice of harmonic driver design shape allows for failure-free and maintenance-free work in space vehicle control systems.
Evolution of Domain-Specific Modeling Language: An Example of an Industrial Case Study on an RT-Sequencer
Authors: Kos Tomaž , Mernik Marjan , Kosar Tomaž
Published: December 2022

Model-driven engineering is a well-established software development methodology that uses models to develop applications where the end-users with visual elements model abstractions from a specific domain. These models are based on domain-specific modeling language (DSML), which is particular to the problem domain. During DSML use, new ideas emerge and DSMLs evolve. However, reports on DSML evolution are rare. This study presents a new DSML called RT-Sequencer that evolved from our DSML Sequencer to support, in addition to the Data Acquisition domain, also a new domain—Real-Time Control (RTC) systems. The process of defining models with a new language RT-Sequencer has changed in a way that new end-users were introduced—advanced end-users, which use general-purpose language (GPL) and advanced programming concepts to define modeling environments for the RT-Sequencer end-users. More specifically, an industrial experience with the RT-Sequencer is presented, where DSML was opened for extension so that a GPL code could be inserted into the model to create new visual blocks for the end-user, and the possibility to adapt and optimize the execution code for a particular task. Our experience shows the specific case of DSML evolution supporting another problem domain, and the implementation effort needed to extend domain-specific modeling language with GPL support.
A Comprehensive Quality Meta-Review of Genetic and Pharmacogenomic Aspects of Medication-Related Osteonecrosis of The Jaw (MRONJ)
Authors: Sacco Roberto , Olate Sergio , Calasans-Maia Monica Diuana , Sacco Nicola , Acocella Alessandro , De Almeida Barros Mourão Carlos Fernando , Moraschini Vittorio , Akintola Oladapo , Guerra Raphael Capelli , Yates Julian
Published: December 2022

Background: Antiresorptive and antiangiogenic medications can cause a serious adverse effect known as medication-related osteonecrosis of the jaw (MRONJ). In recent years, a new trend of research has emerged emphasizing the potential relation of MRONJ and genetic predisposition. Current evidence-based science of this adverse reaction is associated with poorly performed studies. Additionally, MRONJ research has recently observed a new trend of studies orientated towards the misuse of reviews. This quality meta-review intends to summarize the results of all systematic reviews and meta-analyses that have been published on MRONJ in relation to genetic and pharmacogenomics risk factors. Methods: The research study protocol was registered into the database of the International Network for the Registration of Systematic Reviews and Meta-Analyses (INPLASY) INPLASY202230002. A comprehensive search across several databases (PubMed, EMBASE, MEDLINE, and CINAHL) was conducted to locate multi-language papers published between January 2003 and November 2022. Data were collected from relevant research studies and appraised in accordance with the precise outcomes described in this evaluation. Results: Only five systematic reviews and meta-analyses were analysed in this meta-review. All the reviews included in this research presented qualities mistakes and shortcomings. Two quality assessment tools (Confidence in Evidence from Reviews of Qualitative research (CERQual) and Assessment of Multiple Systematic Reviews 2 (AMSTAR-2)) were used to evaluate each study included in this research. Conclusions: The data evaluated by this meta-review confirmed the poor-quality secondary research underpinning the genetic/pharmacogenomics aspect of MRONJ. Moreover, this study highlighted the many flaws of the current published systematic and meta-analysis studies published so far.
Chemical Composition and Antioxidant Activity of Asteraceae Family Plants
Authors: Piątkowska Ewa , Biel Wioletta , Witkowicz Robert , Kępińska-Pacelik Jagoda
Published: December 2022

Plants of the Asteraceae family have been used in traditional medicine for thousands of years. Now, forgotten for some time, they are gaining popularity again. The aim of this study was to determine and compare the proximate composition and antioxidant activity of inflorescences and leaves of Taraxacum officinale F.H. Wigg. (common dandelion), Tanacetum vulgare L. (tansy) and Solidago virgaurea L. (European goldenrod). The content of dry matter, crude protein, crude ash and crude fat was determined according to the Association of Official Analytical Chemists (AOAC). The content of total polyphenols was determined using methanol extracts. Antioxidant activity was determined by three methods. The protein content was the highest in Taraxacum officinale. The fat and ash content increased in the sequence of Solidago virgaurea < Tanacetum vulgare < Taraxacum officinale. The total content of polyphenols in the material and its antioxidant activity (AA) were different between species. Changes were also observed in the morphological parts of the plants. The results of the research encourage the use of not only those parts of plants known but also inflorescences or leaves, which can be excellent ingredients for drugs and other preparations used in medicine or cosmetology and also in the food industry.
Enhancement of the Magnetic Properties in Si4+-Li+-Substituted M-Type Hexaferrites for Permanent Magnets
Authors: You Jin-Young , Lee Kang-Hyuk , Kang Young-Min , Yoo Sang-Im
Published: December 2022

A series of charge-balanced Si4+-M1+,2+ (M = Mg2+, K+, Li+) substitution compositions with the chemical formulae of SrFe12−2xSixMgxO19 (x = 0, 0.05, 0.1, 0.2), Sr1−yFe12−ySiyKyO19 (y = 0.05, 0.1, 0.2), and SrFe12−z(Si0.6Li0.6)zO19 (z = 0.05, 0.1, 0.2, 0.4, 0.6) were prepared using conventional ceramic processes. While the sole doping of Si with x = 0.1 (SrFe12−xSixO19 (x = 0.1)) causes a noticeable Fe2O3 phase formation, the co-doping of Si-Mg and Si-Li allow a single M-type phase formation with x up to x = 0.1 and z = 0.4, respectively. Notably, a 2.6% increase in the saturation magnetization was obtained for Si-Li-substituted SrM with z = 0.05—that is, SrFe11.95Si0.03Li0.03O19. Enhancement of the magnet performance can also be achieved when anisotropic permanent magnets are fabricated based on the substitution composition SrFe11.95Si0.03Li0.03O19. The remnant magnetic flux density was improved by 2.5% compared to that of the unsubstituted SrM (from 4207 to 4314 G). The maximum energy product (BHmax) value also increased from 4.24 to 4.46 M·G·Oe. The enhancement in permanent magnet performance is attributed to the increase in the MS of SrM by the optimal Si-Li substitution. This is a promising result because enhanced permanent magnet performance is achieved with intrinsic magnetic property improvement.
Boronium Salt as an Antiviral Agent against Enveloped Viruses Influenza A and SARS-CoV-2
Authors: Ravine Terrence J. , Rayner Jonathan O. , Roberts Rosemary W. , Davis James H. , Soltani Mohammad
Published: December 2022

Quaternary ammonium compounds (QACs) are routinely used as disinfectants in a variety of settings. They are generally effective against a wide range of microbes but often exhibit undesirable toxicity. Consequently, companies are constantly seeking alternatives to QACs that are just as effective but with reduced health and environmental hazards. Two boronium salt derivatives were tested against influenza A and SARS-CoV-2 viruses. One salt possessed a terminal benzyl group, while the other lacked the same terminal benzyl group. Both salts demonstrated virus inactivation similar to a commercial QAC disinfectant. The non-benzylated form exhibited the same cell toxicity profile as the QAC. However, the benzylated form displayed less cell toxicity than both the non-benzylated form and QAC. These results suggest that the boronium salts may be suitable for use as a disinfecting agent against enveloped viruses in lieu of using a QAC. Continued evaluation of the boronium salts is warranted to determine the lowest effective concentration capable of effectively controlling influenza A and SARS-CoV-2 viruses that also demonstrates low cytotoxicity.
Effect of Window Openable Area and Shading on Indoor Thermal Comfort and Energy Efficiency in Residential Buildings with Various Operating Modes
Authors: Ran Jiandong , Xiong Ke , Dou Mei , Zhong Huizhi , Feng Ya , Tang Mingfang , Yang Zhenjing
Published: December 2022

Solar heat gain and natural ventilation cooling of the indoor environment in buildings are highly influenced by the shading and openable area of windows. In addition to the ambient condition, the Heating, ventilation and air conditioning (HVAC) system’s mode of use can affect the windows’ performance, especially when multiple modes are used in combination (mixed-mode). Although many studies have investigated the mixed-mode application, their conditions for starting/shutting down HVAC equipment and controlling window ventilation are inconsistent with the relevant codes. Here, we propose a mixed-mode operation that resolves the gap between the air conditioning operation temperature and the adaptive comfort upper temperature. It investigates residential buildings’ indoor thermal environment and energy efficiency by combining the effective ventilation opening area ratio (REV) and shading design. Simulation results show that our mixed-mode can reduce the indoor overheating hours by about 50% and the building’s energy consumption by about 50%. We thereby conclude that the openable area of exterior windows in residential buildings in Chongqing should not be less than 10% of the room’s floor axis area where the exterior windows are located. In general, our study expands the existing knowledge of passive energy-saving measures and provides a method for further research on building energy design in hot summer and cold winter regions.
A Systems Biology and LASSO-Based Approach to Decipher the Transcriptome–Interactome Signature for Predicting Non-Small Cell Lung Cancer
Authors: Ahmed Firoz , Khan Abdul Arif , Ansari Hifzur Rahman , Haque Absarul
Published: December 2022

The lack of precise molecular signatures limits the early diagnosis of non-small cell lung cancer (NSCLC). The present study used gene expression data and interaction networks to develop a highly accurate model with the least absolute shrinkage and selection operator (LASSO) for predicting NSCLC. The differentially expressed genes (DEGs) were identified in NSCLC compared with normal tissues using TCGA and GTEx data. A biological network was constructed using DEGs, and the top 20 upregulated and 20 downregulated hub genes were identified. These hub genes were used to identify signature genes with penalized logistic regression using the LASSO to predict NSCLC. Our model’s development involved the following steps: (i) the dataset was divided into 80% for training (TR) and 20% for testing (TD1); (ii) a LASSO logistic regression analysis was performed on the TR with 10-fold cross-validation and identified a combination of 17 genes as NSCLC predictors, which were used further for development of the LASSO model. The model’s performance was assessed on the TD1 dataset and achieved an accuracy and an area under the curve of the receiver operating characteristics (AUC-ROC) of 0.986 and 0.998, respectively. Furthermore, the performance of the LASSO model was evaluated using three independent NSCLC test datasets (GSE18842, GSE27262, GSE19804) and achieved high accuracy, with an AUC-ROC of >0.99, >0.99, and 0.95, respectively. Based on this study, a web application called NSCLCpred was developed to predict NSCLC.
Local Attraction of Substrates and Co-Substrates Enhances Weak Acid and Base Transmembrane Transport
Authors: Epalle Nathan Hugo , Beitz Eric
Published: December 2022

The transmembrane transport of weak acid and base metabolites depends on the local pH conditions that affect the protonation status of the substrates and the availability of co-substrates, typically protons. Different protein designs ensure the attraction of substrates and co-substrates to the transporter entry sites. These include electrostatic surface charges on the transport proteins and complexation with seemingly transport-unrelated proteins that provide substrate and/or proton antenna, or enzymatically generate substrates in place. Such protein assemblies affect transport rates and directionality. The lipid membrane surface also collects and transfers protons. The complexity in the various systems enables adjustability and regulation in a given physiological or pathophysiological situation. This review describes experimentally shown principles in the attraction and facilitation of weak acid and base transport substrates, including monocarboxylates, ammonium, bicarbonate, and arsenite, plus protons as a co-substrate.
Development and Application of an SPR Nanobiosensor Based on AuNPs for the Detection of SARS-CoV-2 on Food Surfaces
Authors: Tessaro Leticia , Aquino Adriano , Panzenhagen Pedro , Ochioni Alan Clavelland , Mutz Yhan S. , Raymundo-Pereira Paulo A. , Vieira Italo Rennan Sousa , Belem Natasha Kilsy Rocha , Conte-Junior Carlos Adam
Published: December 2022

A new transmission route of SARS-CoV-2 through food was recently considered by the World Health Organization (WHO), and, given the pandemic scenario, the search for fast, sensitive, and low-cost methods is necessary. Biosensors have become a viable alternative for large-scale testing because they overcome the limitations of standard techniques. Herein, we investigated the ability of gold spherical nanoparticles (AuNPs) functionalized with oligonucleotides to detect SARS-CoV-2 and demonstrated their potential to be used as plasmonic nanobiosensors. The loop-mediated isothermal amplification (LAMP) technique was used to amplify the viral genetic material from the raw virus-containing solution without any preparation. The detection of virus presence or absence was performed by ultraviolet–visible (UV–Vis) absorption spectroscopy, by monitoring the absorption band of the surface plasmonic resonance (SPR) of the AuNPs. The displacement of the peak by 525 nm from the functionalized AuNPs indicated the absence of the virus (particular region of gold). On the other hand, the region ~300 nm indicated the presence of the virus when RNA bound to the functionalized AuNPs. The nanobiosensor system was designed to detect a region of the N gene in a dynamic concentration range from 0.1 to 50 × 103 ng·mL−1 with a limit of detection (LOD) of 1 ng·mL−1 (2.7 × 103 copy per µL), indicating excellent sensitivity. The nanobiosensor was applied to detect the SARS-CoV-2 virus on the surfaces of vegetables and showed 100% accuracy compared to the standard quantitative reverse transcription polymerase chain reaction (RT-qPCR) technique. Therefore, the nanobiosensor is sensitive, selective, and simple, providing a viable alternative for the rapid detection of SARS-CoV-2 in ready-to-eat vegetables.
Single-Particle Optical Imaging for Ultrasensitive Bioanalysis
Authors: Liu Yujie , Li Binxiao , Liu Baohong , Zhang Kun
Published: December 2022

The quantitative detection of critical biomolecules and in particular low-abundance biomarkers in biofluids is crucial for early-stage diagnosis and management but remains a challenge largely owing to the insufficient sensitivity of existing ensemble-sensing methods. The single-particle imaging technique has emerged as an important tool to analyze ultralow-abundance biomolecules by engineering and exploiting the distinct physical and chemical property of individual luminescent particles. In this review, we focus and survey the latest advances in single-particle optical imaging (OSPI) for ultrasensitive bioanalysis pertaining to basic biological studies and clinical applications. We first introduce state-of-the-art OSPI techniques, including fluorescence, surface-enhanced Raman scattering, electrochemiluminescence, and dark-field scattering, with emphasis on the contributions of various metal and nonmetal nano-labels to the improvement of the signal-to-noise ratio. During the discussion of individual techniques, we also highlight their applications in spatial–temporal measurement of key biomarkers such as proteins, nucleic acids and extracellular vesicles with single-entity sensitivity. To that end, we discuss the current challenges and prospective trends of single-particle optical-imaging-based bioanalysis.
Granger-Causality-Based Multi-Frequency Band EEG Graph Feature Extraction and Fusion for Emotion Recognition
Authors: Zhang Jing , Zhang Xueying , Chen Guijun , Zhao Qing
Published: December 2022

Graph convolutional neural networks (GCN) have attracted much attention in the task of electroencephalogram (EEG) emotion recognition. However, most features of current GCNs do not take full advantage of the causal connection between the EEG signals in different frequency bands during the process of constructing the adjacency matrix. Based on the causal connectivity between the EEG channels obtained by Granger causality (GC) analysis, this paper proposes a multi-frequency band EEG graph feature extraction and fusion method for EEG emotion recognition. First, the original GC matrices between the EEG signals at each frequency band are calculated via GC analysis, and then they are adaptively converted to asymmetric binary GC matrices through an optimal threshold. Then, a kind of novel GC-based GCN feature (GC-GCN) is constructed by using differential entropy features and the binary GC matrices as the node values and adjacency matrices, respectively. Finally, on the basis of the GC-GCN features, a new multi-frequency band feature fusion method (GC-F-GCN) is proposed, which integrates the graph information of the EEG signals at different frequency bands for the same node. The experimental results demonstrate that the proposed GC-F-GCN method achieves better recognition performance than the state-of-the-art GCN methods, for which average accuracies of 97.91%, 98.46%, and 98.15% were achieved for the arousal, valence, and arousal–valence classifications, respectively.
Free-Form Shape Optimization of Advanced High-Strength Steel Members
Authors: Yin Lingfeng , Deng Tianyang , Niu Yu , Li Zhanjie
Published: December 2022

The high yielding strength of advanced high-strength steel (AHSS) provides great opportunities for cold-formed steel (CFS) members with much higher load-carrying capability. However, if manufactured into the traditional cross-section shapes, such as C and Z, the material advantage cannot be fully exploited due to the cross-section instabilities. The purpose of this study was to establish a shape optimization method for cold-formed sections with AHSS and explore the potentially material efficiency that AHSS could provide to these sections in terms of their axial strength. In this study, the insights provided from the elastic buckling analysis and nonlinear finite element (FE) simulations of a set of traditional CFS sections were employed to determine the appropriate section size and length for optimization. Then, the optimization method was established using the particle swarm optimization (PSO) algorithm with the integration of computational analysis through CUFSM and the design approach (i.e., the direct strength method, DSM). The objective function is the maximum axial strength of the CFS sections manufactured with AHSS using the same amount of material (i.e., the same cross-section area). Finally, the optimal sections were simulated and verified by FE analysis, and the characteristics of the optimal cross-sections were analyzed. Overall, the optimization method in this paper achieved good optimization results with greatly improved axial strength capacity from the optimal sections.
Shaking Table Testing of a Low-Rise Reinforced Concrete Intermediate Moment Resisting Frame
Authors: Hussain Sida , Shakeel Hamna , Ali Asif , Rizwan Muhammad , Ahmad Naveed
Published: December 2022

Multi-level shaking table tests were performed on a 1:3 reduced scale two-story reinforced concrete (RC) intermediate moment resisting frame (IMRF) conforming to the requirements given in the ACI-318-19. The exterior joints lacked shear reinforcement to assess the viability of the ACI model recommended for determining the design shear strength of the beam–column joint panel. One of the horizontal components of the 1994 Northridge earthquake accelerogram (090 CDMG Station 24278, Source: PEER strong motion database) was input to the frame for multi-level shaking table testing. Plastic hinges developed in beams under base input motion with a maximum acceleration equal to 0.40 g. The exterior joints incurred extensive damage under base input motion with a maximum acceleration equal to 0.70 g. The frame achieved displacement ductility and overstrength factors (determined as the ratio of the maximum resistance of the frame to the design base share force) equal to 2.40 and 2.50, respectively. This gives a response modification factor equal to 6. The satisfactory performance of the frame is attributed to the high efficiency of the beam–column joint, which was confined by spandrel beams on two faces and the high strength of the concrete. The inherent minimal confinement is sufficient to ensure satisfactory seismic behavior. The analysis confirmed overstrength equal to 1.58 for joint shear strength in comparison to the design strength determined using the ACI model. The data might serve as a reference for calibrating and validating numerical modeling techniques for performance evaluation, which are crucial in the context of performance-based engineering.
Assessing Accessibility and Social Equity of Tertiary Hospitals for Older Adults: A City-Wide Study of Tianjin, China
Authors: Chen Yuan , Ding Qiushi , Shen Yinghua
Published: December 2022

Building age-friendly cities with good accessibility and social equity can help improve older adults’ well-being and quality of life. However, current accessibility analysis of service facilities tends to target most general users, while few studies have been conducted regarding hospitals from an age-friendly perspective. This study aims to measure accessibility to tertiary hospitals and conduct its equity analysis for older adults aged 65 years or over. First, the gravity-based model and geographic information system are utilized to measure accessibility to tertiary hospitals within regions and across regions, and the overall accessibility of a region. Second, coefficient of variation and global Moran’s I are adopted to investigate differences in accessibility to tertiary hospitals by type among regions. Third, Lorenz curves and Gini coefficients are employed to analyze social equity of access to medical services for the elderly. Taking Tianjin, China as the case study, the results show that there exist spatial clusters in terms of accessibility to tertiary hospitals within districts, across districts, and of the whole district. Most districts in the city center have better access to these hospitals than the peripheral and suburban districts. The social equity of accessibility to tertiary hospitals is slightly better in the senior population than in the total population. This study can help the governments improve the spatial distribution and allocation of urban health care resources in a more equitable manner and promote the development of age-friendly cities in future.
Ewing Sarcoma as Secondary Malignant Neoplasm—Epidemiological and Clinical Analysis of an International Trial Registry
Authors: Zöllner Stefan K. , Kauertz Katja L. , Kaiser Isabelle , Kerkhoff Maximilian , Schaefer Christiane , Tassius Madita , Jabar Susanne , Jürgens Heribert , Ladenstein Ruth , Kühne Thomas , Haveman Lianne M. , Paulussen Michael , Ranft Andreas , Dirksen Uta
Published: December 2022

Ewing sarcoma (EwS) is the second most common bone and soft tissue tumor, affecting primarily adolescents and young adults. Patients with secondary EwS are excluded from risk stratification in several studies and therefore do not benefit from new therapies. More knowledge about patients with EwS as secondary malignant neoplasms (SMN) is needed to identify at-risk patients and adapt follow-up strategies. Epidemiology, clinical characteristics, and survival analyses of EwS as SMN were analyzed in 3844 patients treated in the last three consecutive international EwS trials, EICESS 92, Euro-E.W.I.N.G. 99, and EWING 2008. Forty-two cases of EwS as SMN (approximately 1.1% of all patients) were reported, preceded by a heterogeneous group of malignancies, mainly acute lymphoblastic leukemias (n = 7) and lymphomas (n = 7). Three cases of EwS as SMN occurred in the presumed radiation field of the primary tumor. The median age at diagnosis of EwS as SMN was 19.4 years (range, 5.9–72) compared with 10.8 years (range, 0.9–51.2) for primary EwS. The median interval between first malignancy and EwS diagnosis was 7.4 years. The 3-year overall survival (OS)/event-free survival (EFS) was 0.69 (SE = 0.09)/0.53 (SE = 0.10) for localized patients and 0.36 (SE = 0.13)/0.29 (SE = 0.12) for metastatic patients (OS: p = 0.02; EFS: p = 0.03). Survival in patients with EwS as SMN did not differ between hematologic or solid primary malignancies. EwS as SMN is rare; however, survival is similar to that of primary EwS, and its risk-adjusted treatment should be curative, especially in localized patients.
Trop-2 as a Therapeutic Target in Breast Cancer
Authors: Sakach Elizabeth , Sacks Ruth , Kalinsky Kevin
Published: December 2022

The emergence of Trop-2 as a therapeutic target has given rise to new treatment paradigms for the treatment of patients with advanced and metastatic breast cancer. Trop-2 is most highly expressed in triple negative breast cancer (TNBC), but the receptor is found across all breast cancer subtypes. With sacituzumab govitecan, the first FDA-approved, Trop-2 inhibitor, providing a survival benefit in patients with both metastatic TNBC and hormone receptor positive breast cancer, additional Trop-2 directed therapies are under investigation. Ongoing studies of combination regimens with immunotherapy, PARP inhibitors, and other targeted agents aim to further harness the effect of Trop-2 inhibition. Current investigations are also underway in the neoadjuvant and adjuvant setting to evaluate the therapeutic benefit of Trop-2 inhibition in patients with early stage disease. This review highlights the significant impact the discovery Trop-2 has had on our patients with heavily pretreated breast cancer, for whom few treatment options exist, and the future direction of novel Trop-2 targeted therapies.
Immunological and Genomic Analysis Reveals Clinically Relevant Distinctions between Angiosarcoma Subgroups
Authors: van Ravensteijn Stefan G. , Versleijen-Jonkers Yvonne M. H. , Hillebrandt-Roeffen Melissa H. S. , Weidema Marije E. , Nederkoorn Maikel J. L. , Bol Kalijn F. , Gorris Mark A. J. , Verrijp Kiek , Kroeze Leonie I. , de Bitter Tessa J. J. , de Voer Richarda M. , Flucke Uta E. , Desar Ingrid M. E.
Published: December 2022

Angiosarcomas (AS) are extremely rare and aggressive vascular malignancies subdivided in de novo primary AS (pAS) and secondary AS (sAS). We hypothesize that the combination of immunological and genomic profiles significantly differs between primary and secondary AS, with potential impact on treatment strategies and a role for immunotherapy. Tumor-infiltrating lymphocytes were analyzed using multiplex immunohistochemistry from 79 pAS and 178 sAS. Median cell density was significantly higher in sAS for CD3+ T-cells (p < 0.001), CD8+ cytotoxic T-cells (p = 0.033), CD4+ T-helper cells (p < 0.001) and FoxP3+ T-regulatory cells (p < 0.001). CD20+ B-cell density was comparable (p = 0.417). Comprehensive genomic profiling was performed in 25 pAS and 25 sAS. A (likely) pathogenic mutation was detected in 80% of pAS vs. 88% of sAS (p = 0.702). Amplifications were found in 15% of pAS vs. 84% of sAS (p < 0.001). DNA damage response (DDR) pathway mutations (p = 0.021) and MYC amplifications (p < 0.001) were predominantly seen in sAS. In conclusion we observed a clear and clinical relevant distinction in immune infiltration and genomic profiles between pAS and sAS. The T-cell infiltrated tumor microenvironment and frequent DDR gene mutations, especially in sAS, warrant clinical trials with immunotherapy.
Identification of Altered Primary Immunodeficiency-Associated Genes and Their Implications in Pediatric Cancers
Authors: Standing Shaelene , Tran Son , Murguia-Favela Luis , Kovalchuk Olga , Bose Pinaki , Narendran Aru
Published: December 2022

Background: Cancer is the leading cause of disease-related mortality in children and malignancies are more frequently observed in individuals with primary immunodeficiencies (PIDs). This study aimed to identify and highlight the molecular mechanisms, such as oncogenesis and immune evasion, by which PID-related genes may lead to the development of pediatric cancers. Method: We implemented a novel bioinformatics framework using patient data from the TARGET database and performed a comparative transcriptome analysis of PID-related genes in pediatric cancers between normal and cancer tissues, gene ontology enrichment, and protein–protein interaction analyses, and determined the prognostic impacts of commonly mutated and differentially expressed PID-related genes. Results: From the Fulgent Genetics Comprehensive Primary Immunodeficiency panel of 472 PID-related genes, 89 genes were significantly differentially expressed between normal and cancer tissues, and 20 genes were mutated in two or more patients. Enrichment analysis highlighted many immune system processes as well as additional pathways in the mutated PID-related genes related to oncogenesis. Survival outcomes for patients with altered PID-related genes were significantly different for 75 of the 89 DEGs, often resulting in a poorer prognosis. Conclusions: Overall, multiple PID-related genes demonstrated the connection between PIDs and cancer development and should be studied further, with hopes of identifying new therapeutic targets.
ACAP1 Deficiency Predicts Inferior Immunotherapy Response in Solid Tumors
Authors: Yi Qiyi , Pu Youguang , Chao Fengmei , Bian Po , Lv Lei
Published: December 2022

Background: ACAP1 plays a key role in endocytic recycling, which is essential for the normal function of lymphocytes. However, the expression and function of ACAP1 in lymphocytes have rarely been studied. Methods: Large-scale genomic data, including multiple bulk RNA-sequencing datasets, single-cell sequencing datasets, and immunotherapy cohorts, were exploited to comprehensively characterize ACAP1 expression, regulation, and function. Gene set enrichment analysis (GSEA) was used to uncover the pathways associated with ACAP1 expression. Eight algorithms, including TIMER, CIBERSORT, CIBERSORT-ABS, QUANTISEQ, xCELL, MCPCOUNTER, EPIC, and TIDE, were applied to estimate the infiltrating level of immune cells. Western blotting, qPCR, and ChIP-PCR were used to validate the findings from bioinformatic analyses. A T-cell co-culture killing assay was used to investigate the function of ACAP1 in lymphocytes. Results: ACAP1 was highly expressed in immune-related tissues and cells and minimally in other tissues. Moreover, single-cell sequencing analysis in tumor samples revealed that ACAP1 is expressed primarily in tumor-infiltrating lymphocytes (TILs), including T, B, and NK cells. ACAP1 expression is negatively regulated by promoter DNA methylation, with its promoter hypo-methylated in immune cells but hyper-methylated in other cells. Furthermore, SPI1 binds to the ACAP1 promoter and positively regulates its expression in immune cells. ACAP1 levels positively correlate with the infiltrating levels of TILs, especially CD8+ T cells, across a broad range of solid cancer types. ACAP1 deficiency is associated with poor prognosis and immunotherapeutic response in multiple cancer types treated with checkpoint blockade therapy (ICT). Functionally, the depletion of ACAP1 by RNA interference significantly impairs the T cell-mediated killing of tumor cells. Conclusions: Our study demonstrates that ACAP1 is essential for the normal function of TILs, and its deficiency indicates an immunologically “cold” status of tumors that are resistant to ICT.
A Review of Noble Metal Catalysts for Catalytic Removal of VOCs
Authors: Chu Shaoqi , Wang Enlai , Feng Fushan , Zhang Changsheng , Jiang Jie , Zhang Qinqin , Wang Fang , Bing Liancheng , Wang Guangjian , Han Dezhi
Published: December 2022

Volatile organic compounds (VOCs) are important precursors for the formation of secondary pollutants, such as fine particulate matter (PM) and ozone (O3), which will lead to severe atmospheric environmental problems to restrict the sustainable development of the social economy. Catalytic oxidation is a safe, eco-friendly, and simple method for eliminating VOCs, which can be converted into CO2 and H2O without the generation of other harmful substances. The fabrication and development of catalysts are very crucial to enhance the catalytic oxidation efficiency of the removal of VOCs. The noble metal catalyst is one of the commonly used catalysts for the catalytic oxidation of VOCs because of the high reaction activity, good stability, poisoning-resistant ability, and easy regeneration. In this review, the research progress of noble metal (Pt, Pd, Au, Ag, and Ir) catalysts for the removal of VOCs in recent years was summarized with the discussion of the influence factors in the preparation process on the catalytic performance. The reaction mechanisms of the removal of VOCs over the corresponding noble metal catalysts were also briefly discussed.
Augmenting the Photocatalytic Performance of Direct Z-Scheme Bi2O3/g-C3N4 Nanocomposite
Authors: Mahalakshmi Krishnasamy , Ranjith Rajendran , Thangavelu Pazhanivel , Priyadharshini Matheshwaran , Palanivel Baskaran , Manthrammel Mohamed Aslam , Shkir Mohd , Diravidamani Barathi
Published: December 2022

Huge demands for photocatalytically efficient visible-light-induced catalysts have spurred widespread interest in building adaptable heterojunctions. Here, we used in situ thermal polymerization to synthesise the Z-scheme Bi2O3/g-C3N4 heterojunction. The optical, structural, chemical, compositional and photocatalytic behaviours of the samples were analysed through various analytical techniques and photocatalytic methylene blue (MB) dye degradation reaction. Among the various ratios of Bi2O3/g-C3N4 heterojunction composites, the 1:1 ratio showed improved visible-light-induced catalytic activity, which attained 91.2% degradation efficiency after 120 min of visible-light exposure. The dye degradation efficiency was calculated under various environmental conditions by varying the dye concentration, solution pH and catalyst dosage. A improved Z-scheme photocatalytic mechanism was proposed in light of the results. A potential mechanism was suggested to explain the photocatalytic activity, and trapping experiments supported it. Last but not least, this strategy might be helpful to prepare the heterojunction photocatalyst for the degradation of organic pigments.
Deactivation and Regeneration of Palladium Catalysts for Hydrogenation Debenzylation of 2,4,6,8,10,12-Hexabenzyl-2,4,6,8,10,12-Hexaazaisowurtzitane (HBIW)
Authors: Zhang Qunfeng , Wang Mei , Qian Jiacheng , Lou Shuyuan , Jin Jianhong , Li Bingcheng , Lu Chunshan , Feng Feng , Lv Jinghui , Wang Qingtao , Li Xiaonian
Published: December 2022

2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (HNIW, also known as CL-20) is an important energetic compound. As one of the representatives of the third generation of energetic materials, it has an excellent performance, providing broad application prospects for the development of new weapons and equipment. The synthesis of CL-20 is usually obtained from 2,4,6,8,10,12-hexabenzyl-2,4,6,8,10,12-hexaazaisowurtzitane (HBIW) through two catalytic hydrogenolysis and debenzylation reactions, followed by nitration. The most critical step is the hydrogenolysis debenzyl-acetylation process of HBIW because this process requires a large amount of expensive palladium-based catalyst, and the catalyst is completely deactivated after one use. In response to this problem, there is no suitable solution at present, resulting in the high cost of the entire synthesis process. Therefore, reducing the production cost of CL-20 by increasing the catalyst stability is one of the current research priorities. By using AAS, XRD, XPS, TEM, BET, TG and other characterization techniques, the reasons for catalyst deactivation were explored. Studies have shown that the main reason for catalyst deactivation is that a large number of blockages accumulate in the pores of the catalyst after the reaction, which greatly weakens the transfer of the reactant HBIW, intermediate substances, and product 2,6,8,12-tetraacetyl-4,10-dibenzyl-2,4,6,8,10,12-hexaazaisowurtzitane (TADBIW) in the catalyst pores, and the blockage may block the active site of the catalyst. A regeneration treatment method for catalyst deactivation was developed. This method uses chloroform and glacial acetic acid as reagents, which, when combined with stirring and ultrasonic operation, finally restores the activity of the Pd(OH)2/C catalyst. The BET and TG parameters of the regenerated catalyst indicate that catalyst textural and structural properties have greatly recovered, indicating that this treatment method can remove the blockages in the catalyst pores.
Photocatalytic CO2 Conversion to Ethanol: A Concise Review
Authors: Li Dezheng , Hao Chunnan , Liu Huimin , Zhang Ruiqi , Li Yuqiao , Guo Jiawen , Vilancuo Clesio Calebe , Guo Jiapeng
Published: December 2022

Photo-catalytically converting the greenhouse gas CO2 into ethanol is an important avenue for the mitigation of climate issues and the utilization of renewable energies. Catalysts play critical roles in the reaction of photocatalytic CO2 conversion to ethanol, and a number of catalysts have been investigated, including semiconductors and plasmonic metal-based catalysts, as well as several other catalysts. In this review, the progress in the development of each category of catalysts is summarized, the current status is reviewed, the remaining challenges are pointed out, and the future research directions are prospected, with the aim being to pave pathways for the rational design of better catalysts.
Tunable Production of Diesel Bio-Blendstock by Rhenium-Catalyzed Hydrogenation of Crude Hexanoic Acid from Grape Pomace Fermentation
Authors: Licursi Domenico , Raspolli Galletti Anna Maria , Antonetti Claudia , Martinez Gonzalo A. , Jones Emma , Bertin Lorenzo , Di Fidio Nicola , Fulignati Sara , Pasini Gianluca , Frigo Stefano
Published: December 2022

The transition from fossil resources to renewable ones represents a pressing need. The acidogenic fermentation of biomass-derived ethanol to carboxylic acids represents a novel and smart possibility, opening the way for the production of further value-added bio-products through cascade chemical approaches. In this work, the hydrogenation of commercial hexanoic acid to give 1-hexanol/hexyl hexanoate mixtures was preliminary studied in the presence of commercial rhenium catalysts (Re2O7 and 5 wt% Re/C), which resulted as mainly active and selective towards 1-hexanol. On the other hand, the use of niobium phosphate as the acid co-catalyst markedly shifted the selectivity towards hexyl hexanoate. Moreover, 5 wt% Re/C and physical mixtures of (5 wt% Re/C + niobium phosphate) were further tested for the hydrogenation of crude hexanoic acid obtained through fermentation of white grape pomace, confirming the promising performance of these catalytic systems and their recyclability. For the first time, the employment of 1-hexanol/hexyl hexanoate mixtures as a diesel blendstock was evaluated, highlighting a significant reduction of soot and CO emissions, without any significant change in the engine performance. The promising properties of these oxygenated additives are favorable for the partial replacement of traditional fossil fuels, in accordance with the short-term goals of EU countries.
Advances in Innate Immunity to Overcome Immune Rejection during Xenotransplantation
Authors: Lu Tian-Yu , Xu Xue-Ling , Du Xu-Guang , Wei Jin-Hua , Yu Jia-Nan , Deng Shou-Long , Qin Chuan
Published: December 2022

Transplantation is an effective approach for treating end-stage organ failure. There has been a long-standing interest in xenotransplantation as a means of increasing the number of available organs. In the past decade, there has been tremendous progress in xenotransplantation accelerated by the development of rapid gene-editing tools and immunosuppressive therapy. Recently, the heart and kidney from pigs were transplanted into the recipients, which suggests that xenotransplantation has entered a new era. The genetic discrepancy and molecular incompatibility between pigs and primates results in barriers to xenotransplantation. An increasing body of evidence suggests that innate immune responses play an important role in all aspects of the xenogeneic rejection. Simultaneously, the role of important cellular components like macrophages, natural killer (NK) cells, and neutrophils, suggests that the innate immune response in the xenogeneic rejection should not be underestimated. Here, we summarize the current knowledge about the innate immune system in xenotransplantation and highlight the key issues for future investigations. A better understanding of the innate immune responses in xenotransplantation may help to control the xenograft rejection and design optimal combination therapies.