bluuebunny/crossref_metadata_2025 huggingface dataset:
Sedation Therapy in Intensive Care Units: Harnessing the Power of Antioxidants to Combat Oxidative Stress
Authors: Inoue Gen , Ohtaki Yuhei , Satoh Kazue , Odanaka Yuki , Katoh Akihito , Suzuki Keisuke , Tomita Yoshitake , Eiraku Manabu , Kikuchi Kazuki , Harano Kouhei , Yagi Masaharu , Uchida Naoki , Dohi Kenji
Published: July 2023

In critically ill patients requiring intensive care, increased oxidative stress plays an important role in pathogenesis. Sedatives are widely used for sedation in many of these patients. Some sedatives are known antioxidants. However, no studies have evaluated the direct scavenging activity of various sedative agents on different free radicals. This study aimed to determine whether common sedatives (propofol, thiopental, and dexmedetomidine (DEX)) have direct free radical scavenging activity against various free radicals using in vitro electron spin resonance. Superoxide, hydroxyl radical, singlet oxygen, and nitric oxide (NO) direct scavenging activities were measured. All sedatives scavenged different types of free radicals. DEX, a new sedative, also scavenged hydroxyl radicals. Thiopental scavenged all types of free radicals, including NO, whereas propofol did not scavenge superoxide radicals. In this retrospective analysis, we observed changes in oxidative antioxidant markers following the administration of thiopental in patients with severe head trauma. We identified the direct radical-scavenging activity of various sedatives used in clinical settings. Furthermore, we reported a representative case of traumatic brain injury wherein thiopental administration dramatically affected oxidative-stress-related biomarkers. This study suggests that, in the future, sedatives containing thiopental may be redeveloped as an antioxidant therapy through further clinical research.
Multi-Walled Carbon Nanotube Array Modified Electrode with 3D Sensing Interface as Electrochemical DNA Biosensor for Multidrug-Resistant Gene Detection
Authors: Chen Ruiting , Chen Hejing , Peng Huaping , Zheng Yanjie , Lin Zhen , Lin Xinhua
Published: July 2023

Drug resistance in cancer is associated with overexpression of the multidrug resistance (MDR1) gene, leading to the failure of cancer chemotherapy treatment. Therefore, the establishment of an effective method for the detection of the MDR1 gene is extremely crucial in cancer clinical therapy. Here, we report a novel DNA biosensor based on an aligned multi-walled carbon nanotube (MWCNT) array modified electrode with 3D nanostructure for the determination of the MDR1 gene. The microstructure of the modified electrode was observed by an atomic force microscope (AFM), which demonstrated that the electrode interface was arranged in orderly needle-shaped protrusion arrays. The electrochemical properties of the biosensor were characterized by cyclic voltammetry (CV), differential pulse voltammetry (DPV), and electrochemical impedance spectroscopy (EIS). Chronocoulometry (CC) was used for the quantitative detection of the MDR1 gene. Taking advantage of the good conductivity and large electrode area of the MWCNT arrays, this electrochemical DNA sensor achieved a dynamic range from 1.0 × 10−12 M to 1.0 × 10−8 M with a minimal detection limit of 6.4 × 10−13 M. In addition, this proposed DNA biosensor exhibited high sensitivity, selectivity, and stability, which may be useful for the trace analysis of the MDR1 gene in complex samples.
The Analogy between Tinnitus and Chronic Pain: A Phenomenological Approach
Authors: Norena Arnaud J.
Published: July 2023

Tinnitus is an auditory sensation without external acoustic stimulation or significance, which may be lived as an unpleasant experience and impact the subject’s quality of life. Tinnitus loudness, which is generally low, bears no relation to distress. Factors other than psychoacoustic (such as psychological factors) are therefore implicated in the way tinnitus is experienced. The aim of this article is to attempt to understand how tinnitus can, like chronic pain, generate a ‘crisis’ in the process of existence, which may go as far as the collapse of the subject. The main idea put forward in the present article is that tinnitus may be compared to the phenomenon of pain from the point of view of the way it is experienced. Although the analogy between tinnitus and pain has often been made in the literature, it has been limited to a parallel concerning putative physiopathological mechanisms and has never really been explored in depth from the phenomenological point of view. Tinnitus is comparable to pain inasmuch as it is felt, not perceived: it springs up (without intention or exploration), abolishes the distance between the subject and the sensation (there is only a subject and no object), and has nothing to say about the world. Like pain, tinnitus is formless and abnormal and can alter the normal order of the world with maximum intensity. Finally, tinnitus and pain enclose the subject within the limits of the body, which then becomes in excess. Tinnitus may be a source of suffering, which affects not only the body but a person’s very existence and, in particular, its deployment in time. Plans are thus abolished, so time is no longer ‘secreted’, it is enclosed in an eternal present. If the crisis triggered by tinnitus is not resolved, the subject may buckle and collapse (depression) when their resources for resisting are depleted. The path may be long and winding from the moment when tinnitus emerges to when it assaults existence and its eventual integration into a new existential norm where tinnitus is no longer a source of disturbance.
Modeling and Quantifying the Impact of Personified Communication on Purchase Behavior in Social Commerce
Authors: Zhao Jie , Zhu Chengxiang
Published: July 2023

The advancement of mobile internet technology has enabled companies to leverage social media for e-commerce, where some use personified images and language to communicate with consumers. This paper investigates how personified communication affects consumer behavior in social commerce and whether consumers are willing to accept this new form of communication. Specifically, the study explores consumers’ willingness to accept personified communication in social commerce, considering the role of cognitive needs in regulating the internal mechanism. The paper proposes suggestions for enterprises to improve their social media communication and presents an improved model based on the Technology Acceptance Model (TAM). The model introduces perceived interaction as a new independent variable and adds cognitive needs as a regulatory variable, which is more suitable for social commerce. The study conducts a questionnaire survey online and analyzes the data using AMOS and SPSS. The results demonstrate that perceived usefulness and perceived interaction positively impact consumers’ attitudes, which subsequently influences their willingness to purchase. Furthermore, cognitive needs as a regulatory variable significantly affect the path from perceived usefulness to attitude and purchase intention.
Measuring State and Trait Anxiety: An Application of Multidimensional Item Response Theory
Authors: Carlucci Leonardo , Innamorati Marco , Ree Melissa , D’Ignazio Giorgia , Balsamo Michela
Published: July 2023

The State-Trait Inventory for Cognitive and Somatic Anxiety (STICSA) is a widely used measure of state and trait anxiety. Within the Classical Testing Theory model, consistent findings provide support for its multidimensional factor structure, discriminant, convergent, and nomological validity, as well as age and gender invariance, across healthy and clinical samples. Nevertheless, some issues regarding STICSA dimensionality and item-scale composition remain unresolved (e.g., both bifactor and two-factor models were found to fit data equally well). The goal of this study was to investigate the STICSA’s dimensionality within the Item Response Theory, and to assess the tenability of the bifactor model as a plausible model over the multidimensional model. The sample consisted of 3338 Italian participants (58.21% females; 41.79% males) with an average age of 35.65 years (range: 18–99; SD = 20.25). Both bifactor and two-correlated dimensions of the STICSA scales were confirmed to fit data by applying the multidimensional Item Response Theory (mIRT). While the bifactor model showed better fit indices, the multidimensional model was more accurate and precise (0.86–0.88) in estimating state and trait latent anxiety. A further comparison between multidimensional item parameters revealed that the multidimensional and bifactor models were equivalent. Findings showed that the STICSA is an accurate and precise instrument for measuring somatic and cognitive symptomatology dimensions within state and trait anxiety. The use of the state/trait total score requires special attention from the clinicians and researchers to avoid bias in the psychodiagnostic assessment.
Precrastination and Time Perspective: Evidence from Intertemporal Decision-Making
Authors: Ma Boyang , Zhang Yong
Published: July 2023

Although procrastination has been extensively studied, precrastination remains an unsolved puzzle. Precrastination is the tendency to start tasks as soon as possible, even at the cost of extra effort. Using the near bucket paradigm with 81 undergraduate students, this study examined the relationship between precrastination and time perspective, proactive personality, and subjects’ differential performance in intertemporal decision-making. The results confirmed the cognitive-load-reduction (CLEAR) hypothesis. Precrastination was found to be positively predicted by the future time dimension of time perspective and negatively predicted by proactive personality. In addition, there is a significant positive correlation between precrastination and delay discounting of intertemporal decision-making, which exists only for the loss situation.
Study on the Impact of a Metro Depot Cover Structure on the Existing Metro Structure and Additional Settlement of Tracks
Authors: Peng Hua , Pang Feiyv , Li Zichen , Xiao Xiaoqi , Tang Shuhe
Published: July 2023

The superstructure of the metro depot is not only convenient for traffic but also solves the land-use problem. However, the construction of the superstructure comes after the metro depot has been put into normal operation. The foundation of the depot is bound to produce secondary settlement. Based on the calculation method of the friction-end bearing pile of Mindlin’s solution in the specification, the superstructure construction project above the Beijing Guogongzhuang metro depot is taken as the basis. Under certain conditions, the settlement of the pile foundation under the action of secondary load and the influence on the track structure are calculated. Moreover, the finite element analysis software ANSYS 18.0 is used to establish the analysis model of the construction of the superstructure of the applied depot. The results show that the influence of the pile foundation settlement produces a certain additional influence on the surrounding tracks, and the maximum value locates at the center of the bearing platform and gradually decreases outward. Under the conditions of informative construction, uniform loading of the structure and control of the construction process, local bias loads and uneven settlements are avoided. The impact of the construction on the track can be effectively controlled, and the impact on the structure can be kept within the allowable limits. By comparing this instance with a number of similar superstructure projects in Beijing, this study shows that the overall risk of this type of project can be controlled and can provide a technical reference for similar superstructure projects on top of a metro depot construction in the future.
Post-Handover Housing Quality Management and Standards in Korea
Authors: Park Junmo , Seo Deokseok
Published: July 2023

Housing quality is a subject of dispute worldwide, and these disputes are increasing due to the significant differences in the views of producers and consumers on quality standards. To arbitrate disputes, an objective evaluation of housing quality is necessary. In Korea, disputes over housing quality in the post-handover stage result in lawsuits, thus becoming a social issue. This study analyzed the results of lawsuits against housing complexes in Korea. The ratio of defect repair cost to construction cost (DRCCC) was adopted as an indicator, and the quality level of the building was evaluated using a control chart to select failures. The findings showed that there were more cases where the construction cost was small, the housing quality was poor, the deviation was wide, and the quality defect exceeded the limit level of the control chart. To improve housing quality, it is necessary to strengthen quality management, to control the quality within the management limit, and to adjust standards by reflecting the consumer’s viewpoint.
Ultraviolet Radiation Transmission in Building’s Fenestration: Part II, Exploring Digital Imaging, UV Photography, Image Processing, and Computer Vision Techniques
Authors: Onatayo Damilola Adeniyi , Srinivasan Ravi Shankar , Shah Bipin
Published: July 2023

The growing demand for sustainable and energy-efficient buildings has highlighted the need for reliable and accurate methods to detect fenestration deterioration and assess UV radiation transmission. Traditional detection techniques, such as spectrophotometers and radiometers, discussed in Part I, are often expensive and invasive, necessitating more accessible and cost-effective solutions. This study, which is Part II, provides an in-depth exploration of the concepts and methodologies underlying UV bandpass-filtered imaging, advanced image processing techniques, and the mechanisms of pixel transformation equations. The aim is to lay the groundwork for a unified approach to detecting ultraviolet (UV) radiation transmission in fenestration glazing. By exploiting the capabilities of digital imaging devices, including widely accessible smartphones, and integrating them with robust segmentation techniques and mathematical transformations, this research paves the way for an innovative and potentially democratized approach to UV detection in fenestration glazing. However, further research is required to optimize and tailor the detection methods and approaches using digital imaging, UV photography, image processing, and computer vision for specific applications in the fenestration industry and detecting UV transmission. The complex interplay of various physical phenomena related to UV radiation, digital imaging, and the unique characteristics of fenestration glazing necessitates the development of a cohesive framework that synergizes these techniques while addressing these intricacies. While extensively reviewing existing techniques, this paper highlights these challenges and sets the direction for future research in the UV imaging domain.
Update in Lung Cancer Molecular Pathology: Technological Advances and Clinical Practice
Authors: Graziano Paolo , Rossi Giulio
Published: July 2023

This Special Issue of eleven articles, including six original works and five reviews, demonstrates the modern heterogenous approach to lung cancer by means of various methodologies from international experts from various countries [...]
The Redox-Active Manganese(III) Porphyrin, MnTnBuOE-2-PyP5+, Impairs the Migration and Invasion of Non-Small Cell Lung Cancer Cells, Either Alone or Combined with Cisplatin
Authors: Soares Rita B. , Manguinhas Rita , Costa João G. , Saraiva Nuno , Gil Nuno , Rosell Rafael , Camões Sérgio P. , Batinic-Haberle Ines , Spasojevic Ivan , Castro Matilde , Miranda Joana P. , Guedes de Pinho Paula , Fernandes Ana S. , Oliveira Nuno G.
Published: July 2023

Manganese(III) porphyrin MnTnBuOE-2-PyP5+ (MnBuOE, BMX-001) is a third-generation redox-active cationic substituted pyridylporphyrin-based drug with a good safety/toxicity profile that has been studied in several types of cancer. It is currently in four phase I/II clinical trials on patients suffering from glioma, head and neck cancer, anal squamous cell carcinoma and multiple brain metastases. There is yet an insufficient understanding of the impact of MnBuOE on lung cancer. Therefore, this study aims to fill this gap by demonstrating the effects of MnBuOE on non-small cell lung cancer (NSCLC) A549 and H1975 cell lines. The cytotoxicity of MnBuOE alone or combined with cisplatin was evaluated by crystal violet (CV) and/or 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphophenyl)-2H-Tetrazolium (MTS) reduction assays. Intracellular ROS levels were assessed using two fluorescent probes. Furthermore, the impact of MnBuOE alone or in combination with cisplatin on collective cell migration, individual chemotactic migration and chemoinvasion was assessed using the wound-healing and transwell assays. The expression of genes related to migration and invasion was assessed through RT-qPCR. While MnBuOE alone decreased H1975 cell viability at high concentrations, when combined with cisplatin it markedly reduced the viability of the more invasive H1975 cell line but not of A549 cell line. However, MnBuOE alone significantly decreased the migration of both cell lines. The anti-migratory effect was more pronounced when MnBuOE was combined with cisplatin. Finally, MnBuOE alone or combined with cisplatin significantly reduced cell invasion. MnBuOE alone or combined with cisplatin downregulated MMP2, MMP9, VIM, EGFR and VEGFA and upregulated CDH1 in both cell lines. Overall, our data demonstrate the anti-metastatic potential of MnBuOE for the treatment of NSCLC.
Definitions, Biology, and Current Therapeutic Landscape of Myelodysplastic/Myeloproliferative Neoplasms
Authors: Gerke Margo B. , Christodoulou Ilias , Karantanos Theodoros
Published: July 2023

Myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are hematological disorders characterized by both proliferative and dysplastic features. According to the 2022 International Consensus Classification (ICC), MDS/MPN consists of clonal monocytosis of undetermined significance (CMUS), chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia (aCML), MDS/MPN with SF3B1 mutation (MDS/MPN-T-SF3B1), MDS/MPN with ring sideroblasts and thrombocytosis not otherwise specified (MDS/MPN-RS-T-NOS), and MDS/MPN-NOS. These disorders exhibit a diverse range of genetic alterations involving various transcription factors (e.g., RUNX1), signaling molecules (e.g., NRAS, JAK2), splicing factors (e.g., SF3B, SRSF2), and epigenetic regulators (e.g., TET2, ASXL1, DNMT3A), as well as specific cytogenetic abnormalities (e.g., 8 trisomies, 7 deletions/monosomies). Clinical studies exploring therapeutic options for higher-risk MDS/MPN overlap syndromes mostly involve hypomethylating agents, but other treatments such as lenalidomide and targeted agents such as JAK inhibitors and inhibitors targeting PARP, histone deacetylases, and the Ras pathway are under investigation. While these treatment modalities can provide partial disease control, allogeneic bone marrow transplantation (allo-BMT) is the only potentially curative option for patients. Important prognostic factors correlating with outcomes after allo-BMT include comorbidities, splenomegaly, karyotype alterations, and the bone marrow blasts percentage at the time of transplantation. Future research is imperative to optimizing therapeutic strategies and enhancing patient outcomes in MDS/MPN neoplasms. In this review, we summarize MDS/MPN diagnostic criteria, biology, and current and future treatment options, including bone marrow transplantation.
G4-QuadScreen: A Computational Tool for Identifying Multi-Target-Directed Anticancer Leads against G-Quadruplex DNA
Authors: Bhat-Ambure Jyotsna , Ambure Pravin , Serrano-Candelas Eva , Galiana-Roselló Cristina , Gil-Martínez Ariadna , Guerrero Mario , Martin Margarita , González-García Jorge , García-España Enrique , Gozalbes Rafael
Published: July 2023

The study presents ‘G4-QuadScreen’, a user-friendly computational tool for identifying MTDLs against G4s. Also, it offers a few hit MTDLs based on in silico and in vitro approaches. Multi-tasking QSAR models were developed using linear discriminant analysis and random forest machine learning techniques for predicting the responses of interest (G4 interaction, G4 stabilization, G4 selectivity, and cytotoxicity) considering the variations in the experimental conditions (e.g., G4 sequences, endpoints, cell lines, buffers, and assays). A virtual screening with G4-QuadScreen and molecular docking using YASARA (AutoDock-Vina) was performed. G4 activities were confirmed via FRET melting, FID, and cell viability assays. Validation metrics demonstrated the high discriminatory power and robustness of the models (the accuracy of all models is ~>90% for the training sets and ~>80% for the external sets). The experimental evaluations showed that ten screened MTDLs have the capacity to selectively stabilize multiple G4s. Three screened MTDLs induced a strong inhibitory effect on various human cancer cell lines. This pioneering computational study serves a tool to accelerate the search for new leads against G4s, reducing false positive outcomes in the early stages of drug discovery. The G4-QuadScreen tool is accessible on the ChemoPredictionSuite website.
Clock-like Mutation Signature May Be Prognostic for Worse Survival Than Signatures of UV Damage in Cutaneous Melanoma
Authors: Fröhlich Fabienne , Ramelyte Egle , Turko Patrick , Dzung Andreas , Freiberger Sandra N. , Mangana Joanna , Levesque Mitchell P. , Dummer Reinhard
Published: July 2023

Novel treatment modalities comprising immune checkpoint inhibitors and targeted therapies have revolutionized treatment of metastatic melanoma. Still, some patients suffer from rapid progression and decease within months after a diagnosis of stage IV melanoma. We aimed to assess whether genomic alterations may predict survival after the development of stage IV disease, irrespective of received therapy. We analyzed tumor samples of 79 patients with stage IV melanoma using a custom next-generation gene-sequencing panel, MelArray, designed to detect alterations in 190 melanoma-relevant genes. We classified the patients: first, as short survivors (survival ≤6 months after stage IV disease, n = 22) and long survivors (survival >6 months, n = 57); second, by using a cut-off of one year; and third, by comparing the longest surviving 20 patients to the shortest surviving 20. Among analyzed genes, no individual gene alterations, or combinations of alterations, could be dichotomously associated with survival. However, the cohort’s mutational profiles closely matched three known mutational signatures curated by the Catalog of Somatic Mutations in Cancer (COSMIC): UV signature COSMIC_7 (cosine-similarity 0.932), clock-like signature COSMIC_5 (cosine-similarity 0.829), and COSMIC_30 (cosine-similarity 0.726). Patients with UV signature had longer survival compared to patients with clock-like and COSMIC 30 (p < 0.0001). Subgroup dichotomization at 6 months showed that 75% of patients with UV signature survived longer than 6 months, and about 75% of patients with clock-like signature survived less than 6 months after development of stage IV disease. In our cohort, clock-like COSMIC_5 mutational signature predicted poor survival while a UV signature COSMIC_7 predicted longer survival. The prognostic value of mutational signatures should be evaluated in prospective studies.
Recent Advances in Clinical Research for Skin Cancer Chemoprevention
Authors: Tow Ruby , Hanoun Samuel , Andresen Bradley , Shahid Ayaz , Wang Jeffrey , Kelly Kristen M. , Meyskens Frank L. , Huang Ying
Published: July 2023

Neoplasm arising from the keratinocytes or melanocytes in the skin is the most prevalent type of cancer in the United States and worldwide. Since ultraviolet (UV) radiation may be a causing factor for several types of skin cancer, effective strategies to manage skin cancer include preventive measures such as minimizing exposure to UV and applying sunscreens. However, the effect of sunscreen in reducing skin cancer incidence remains uncertain. An alternative approach to prevent skin cancer is chemoprevention, which is defined as using either natural products or synthetic compounds to inhibit, delay, or reverse the development of cancer. Preclinical studies have demonstrated the effectiveness of multiple pharmacological agents and dietary supplements. However, whether preclinical findings can be translated into clinical application is unknown. This review evaluates the state of recent clinical trials investigating chemopreventive agents focusing on skin cancer to compare the target populations, interventions, endpoints, and outcomes of these trials. The ClinicalTrials and PubMed databases were searched for their available literature using the key words “skin cancer” and “chemoprevention”. The objective of this review is to provide updated information on the effectiveness and side effects of promising chemopreventive agents in human subjects and to identify research gaps.
Extraintestinal Cancers in Inflammatory Bowel Disease: A Literature Review
Authors: Massano Alessandro , Bertin Luisa , Zingone Fabiana , Buda Andrea , Visaggi Pierfrancesco , Bertani Lorenzo , de Bortoli Nicola , Fassan Matteo , Scarpa Marco , Ruffolo Cesare , Angriman Imerio , Bezzio Cristina , Casini Valentina , Ribaldone Davide Giuseppe , Savarino Edoardo Vincenzo , Barberio Brigida
Published: July 2023

Background: Inflammatory bowel disease (IBD) is a group of chronic multifactorial inflammatory disorders including two major entities: Crohn’s disease (CD) and ulcerative colitis (UC). Preliminary evidence suggests that patients with IBD may be at increased risk of developing intestinal and extraintestinal cancers (EICs). Actually, little is known about the association between IBD and EICs, and there is ever-growing concern regarding the safety of immunomodulators and biological therapy, which may represent a risk factor for carcinogenesis. Aims: The aim of this review is to summarize the evidence regarding the association between IBD and EICs, the safety of immunomodulators and biological therapy and the management of immunomodulators and biologic agents in IBD patients with prior or current EICs. Results: IBD patients have a higher risk of developing different forms of extraintestinal solid organ tumors and hematological malignancies. Immunomodulators and biological therapy may increase the risk of developing some types of EICs and may be consciously used in patients with IBD and current or prior history of malignancy. Conclusions: Decisions regarding the use of immunomodulators or biological therapies should be made on an individual basis, considering a multidisciplinary approach involving oncologists.
Elafin as a Prognostic Marker in Esophageal Squamous Cell Carcinoma: A Pilot Study Using Three-Dimensional Imaging and Genomic Profiling
Authors: Chen Wei-Chung , Wu Chun-Chieh , Liu Yu-Peng , Zhuo Guan-Yu , Wang Yao-Kuang , Chen Yi-Hsun , Chen Chu-Chih , Wang Yin-Han , Wu Ming-Tsang , Wu I-Chen
Published: July 2023

Esophageal cancers are globally the sixth deadliest malignancy, with limited curative options. The association of high serum elafin levels, a molecule produced by epithelial cells, with esophageal squamous cell carcinoma (ESCC) risk is established, but its link to poor ESCC prognosis remains unclear. To explore this question, we first used three-dimensional confocal imaging to create a model of the spatial distribution of elafin inside locoregional ESCC tissues. Then, after analyzing data obtained from whole-genome microarrays for ESCC cell lines and their more invasive sublines, we performed in vitro experiments using RNA sequencing to identify possible elafin-related pathways. Three-dimensional tissue imaging showed elafin distributed as an interweaved-like fibrous structure in the stroma of tissue obtained from patients with high serum levels of elafin and poorer prognoses. By contrast, the signal was confined inside or around the tumor nest in patients who had lower serum levels and better survival. The analysis of a TCGA dataset revealed that higher levels of elafin mRNA in stage I–IIIA ESCC patients were associated with shorter survival. The in vitro studies revealed that elafin promoted ESCC cell proliferation, migration, and invasion via the epithelial–mesenchymal transition pathway. Thus, elafin inhibition could potentially be used therapeutically to improve survival in patients with locoregional ESCC.
Editorial for “Impact of Regorafenib on Endothelial Transdifferentiation of Glioblastoma Stem-like Cells”
Authors: Kolothara Unnikrishnan Madhukrishna , Schmidt Mirko H. H.
Published: July 2023

Glioblastoma multiforme (GBM) is the most frequently occurring form of malignant primary brain tumor in adults [...]
CMGC Kinases in Health and Cancer
Authors: Chowdhury Iftekhar , Dashi Giovanna , Keskitalo Salla
Published: July 2023

CMGC kinases, encompassing cyclin-dependent kinases (CDKs), mitogen-activated protein kinases (MAPKs), glycogen synthase kinases (GSKs), and CDC-like kinases (CLKs), play pivotal roles in cellular signaling pathways, including cell cycle regulation, proliferation, differentiation, apoptosis, and gene expression regulation. The dysregulation and aberrant activation of these kinases have been implicated in cancer development and progression, making them attractive therapeutic targets. In recent years, kinase inhibitors targeting CMGC kinases, such as CDK4/6 inhibitors and BRAF/MEK inhibitors, have demonstrated clinical success in treating specific cancer types. However, challenges remain, including resistance to kinase inhibitors, off-target effects, and the need for better patient stratification. This review provides a comprehensive overview of the importance of CMGC kinases in cancer biology, their involvement in cellular signaling pathways, protein–protein interactions, and the current state of kinase inhibitors targeting these kinases. Furthermore, we discuss the challenges and future perspectives in targeting CMGC kinases for cancer therapy, including potential strategies to overcome resistance, the development of more selective inhibitors, and novel therapeutic approaches, such as targeting protein–protein interactions, exploiting synthetic lethality, and the evolution of omics in the study of the human kinome. As our understanding of the molecular mechanisms and protein–protein interactions involving CMGC kinases expands, so too will the opportunities for the development of more selective and effective therapeutic strategies for cancer treatment.
Recurrence of Basal Cell Carcinoma Treated with Surgical Excision and Histopathological Analysis with Frozen Section Technique with Complete Margin Control (CMC-FS): A 15-Year Experience of a Reference Center
Authors: Di Maria Alessandra , Barone Gianmaria , Ferraro Vanessa , Tredici Costanza , Manara Sofia , De Carlo Camilla , Gaeta Alessandro , Confalonieri Filippo
Published: July 2023

Background: Basal cell carcinoma (BCC) is the most common type of eyelid malignancy and it is considered to be dangerous due to its proximity to functionally essential organs. Early diagnosis and complete excision of the primary lesion are crucial to prevent infiltration and metastasis. The study aims to evaluate the extent of recurrence in subjects affected by BCC of the upper third of the face treated with surgical eradication and the frozen section technique with complete margin control (CMC-FS), in comparison with the gold standard Mohs micrographic surgery (MMS). Materials and Methods: The study included 111 patients with 111 biopsy-proven eyelid BCCs. On clinical examination, all lesions were removed with 2 mm margins clinically free of neoplasm. Prior to reconstruction, CMC-FS analysis of all surgical margins was performed on each tumor for histopathologic confirmation. Subsequently, all margins were presented for the permanent paraffin sections. Results: There were 69 primary carcinomas and 42 secondary carcinomas among the 111 samples. No recurrence occurred in 109 tumors followed-up for at least 5 years, with a total recurrence rate of 1.8%. The median time between lesion excision and diagnosis of recurrence was 20 months. Conclusions: at 5-year follow-up, CMC-FS guided excision of BCCs of the eyelids resulted in recurrence rates equivalent to MMS. Intraoperative microscopic control of all margins reduced the recurrence rate of the upper third of the facial BCCs, correlating with easier reconstruction with better esthetic and functional outcome.
A Machine Learning Approach Using FDG PET-Based Radiomics for Prediction of Tumor Mutational Burden and Prognosis in Stage IV Colorectal Cancer
Authors: Lee Hyunjong , Moon Seung Hwan , Hong Jung Yong , Lee Jeeyun , Hyun Seung Hyup
Published: July 2023

Introduction: We assessed the performance of F-18 fluorodeoxyglucose positron emission tomography (FDG PET)-based radiomics for the prediction of tumor mutational burden (TMB) and prognosis using a machine learning (ML) approach in patients with stage IV colorectal cancer (CRC). Methods: Ninety-one CRC patients who underwent pretreatment FDG PET/computed tomography (CT) and palliative chemotherapy were retrospectively included. PET-based radiomics were extracted from the primary tumor on PET imaging using the software LIFEx. For feature selection, PET-based radiomics associated with TMB were selected by logistic regression analysis. The performances of seven ML algorithms to predict high TMB were compared by the area under the receiver’s operating characteristic curves (AUCs) and validated by five-fold cross-validation. A PET radiomic score was calculated by averaging the z-score of each radiomic feature. The prognostic power of the PET radiomic score was assessed using Cox proportional hazards regression analysis. Results: Ten significant radiomic features associated with TMB were selected: surface-to-volume ratio, total lesion glycolysis, tumor volume, area, compacity, complexity, entropy, correlation, coarseness, and zone size non-uniformity. The k-nearest neighbors model obtained the good performance for prediction of high TMB (AUC: 0.791, accuracy: 0.814, sensitivity: 0.619, specificity: 0.871). On multivariable Cox regression analysis, the PET radiomic score (Hazard ratio = 4.498, 95% confidential interval = 1.024–19.759; p = 0.046) was a significant independent prognostic factor for OS. Conclusions: This study demonstrates that PET-based radiomics are useful image biomarkers for the prediction of TMB status in stage IV CRC. PET radiomic score, which integrates significant radiomic features, has the potential to predict survival in stage IV CRC patients.
Analytical Models for Measuring the Mechanical Properties of Yeast
Authors: Savin Nikita , Erofeev Alexander , Gorelkin Petr
Published: July 2023

The mechanical properties of yeast play an important role in many biological processes, such as cell division and growth, maintenance of internal pressure, and biofilm formation. In addition, the mechanical properties of cells can indicate the degree of damage caused by antifungal drugs, as the mechanical parameters of healthy and damaged cells are different. Over the past decades, atomic force microscopy (AFM) and micromanipulation have become the most widely used methods for evaluating the mechanical characteristics of microorganisms. In this case, the reliability of such an estimate depends on the choice of mathematical model. This review presents various analytical models developed in recent years for studying the mechanical properties of both cells and their individual structures. The main provisions of the applied approaches are described along with their limitations and advantages. Attention is paid to the innovative method of low-invasive nanomechanical mapping with scanning ion-conductance microscopy (SICM), which is currently starting to be successfully used in the discovery of novel drugs acting on the yeast cell wall and plasma membrane.
Inducible Rbpms-CreERT2 Mouse Line for Studying Gene Function in Retinal Ganglion Cell Physiology and Disease
Authors: Guo Luming , Xie Xiaoling , Wang Jing , Xiao Haiyan , Li Shuchun , Xu Mei , Quainoo Ebenezer , Koppaka Rithwik , Zhuo Jiaping , Smith Sylvia B. , Gan Lin
Published: July 2023

Retinal ganglion cells (RGCs) are the sole output neurons conveying visual stimuli from the retina to the brain, and dysfunction or loss of RGCs is the primary determinant of visual loss in traumatic and degenerative ocular conditions. Currently, there is a lack of RGC-specific Cre mouse lines that serve as invaluable tools for manipulating genes in RGCs and studying the genetic basis of RGC diseases. The RNA-binding protein with multiple splicing (RBPMS) is identified as the specific marker of all RGCs. Here, we report the generation and characterization of a knock-in mouse line in which a P2A-CreERT2 coding sequence is fused in-frame to the C-terminus of endogenous RBPMS, allowing for the co-expression of RBPMS and CreERT2. The inducible Rbpms-CreERT2 mice exhibited a high recombination efficiency in activating the expression of the tdTomato reporter gene in nearly all adult RGCs as well as in differentiated RGCs starting at E13.5. Additionally, both heterozygous and homozygous Rbpms-CreERT2 knock-in mice showed no detectable defect in the retinal structure, visual function, and transcriptome. Together, these results demonstrated that the Rbpms-CreERT2 knock-in mouse can serve as a powerful and highly desired genetic tool for lineage tracing, genetic manipulation, retinal physiology study, and ocular disease modeling in RGCs.
Genetic Downregulation of the Metabotropic Glutamate Receptor Type 5 Dampens the Reactive and Neurotoxic Phenotype of Adult ALS Astrocytes
Authors: Torazza Carola , Provenzano Francesca , Gallia Elena , Cerminara Maria , Balbi Matilde , Bonifacino Tiziana , Tessitore Sara , Ravera Silvia , Usai Cesare , Musante Ilaria , Puliti Aldamaria , Van Den Bosch Ludo , Jafar-nejad Paymaan , Rigo Frank , Milanese Marco , Bonanno Giambattista
Published: July 2023

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive degeneration of motor neurons (MNs). Astrocytes display a toxic phenotype in ALS, which results in MN damage. Glutamate (Glu)-mediated excitotoxicity and group I metabotropic glutamate receptors (mGluRs) play a pathological role in the disease progression. We previously demonstrated that in vivo genetic ablation or pharmacological modulation of mGluR5 reduced astrocyte activation and MN death, prolonged survival and ameliorated the clinical progression in the SOD1G93A mouse model of ALS. This study aimed to investigate in vitro the effects of mGluR5 downregulation on the reactive spinal cord astrocytes cultured from adult late symptomatic SOD1G93A mice. We observed that mGluR5 downregulation in SOD1G93A astrocytes diminished the cytosolic Ca2+ overload under resting conditions and after mGluR5 simulation and reduced the expression of the reactive glial markers GFAP, S100β and vimentin. In vitro exposure to an anti-mGluR5 antisense oligonucleotide or to the negative allosteric modulator CTEP also ameliorated the altered reactive astrocyte phenotype. Downregulating mGluR5 in SOD1G93A mice reduced the synthesis and release of the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α and ameliorated the cellular bioenergetic profile by improving the diminished oxygen consumption and ATP synthesis and by lowering the excessive lactate dehydrogenase activity. Most relevantly, mGluR5 downregulation hampered the neurotoxicity of SOD1G93A astrocytes co-cultured with spinal cord MNs. We conclude that selective reduction in mGluR5 expression in SOD1G93A astrocytes positively modulates the astrocyte reactive phenotype and neurotoxicity towards MNs, further supporting mGluR5 as a promising therapeutic target in ALS.
Differential Modulation of miR-122 Transcription by TGFβ1/BMP6: Implications for Nonresolving Inflammation and Hepatocarcinogenesis
Authors: Paluschinski Martha , Kordes Claus , Vucur Mihael , Buettner Veronika , Roderburg Christoph , Xu Haifeng C. , Shinte Prashant V. , Lang Philipp A. , Luedde Tom , Castoldi Mirco
Published: July 2023

Chronic inflammation is widely recognized as a significant factor that promotes and worsens the development of malignancies, including hepatocellular carcinoma. This study aimed to explore the potential role of microRNAs in inflammation-associated nonresolving hepatocarcinogenesis. By conducting a comprehensive analysis of altered microRNAs in animal models with liver cancer of various etiologies, we identified miR-122 as the most significantly downregulated microRNA in the liver of animals with inflammation-associated liver cancer. Although previous research has indicated the importance of miR-122 in maintaining hepatocyte function, its specific role as either the trigger or the consequence of underlying diseases remains unclear. Through extensive analysis of animals and in vitro models, we have successfully demonstrated that miR-122 transcription is differentially regulated by the immunoregulatory cytokines, by the transforming growth factor-beta 1 (TGFβ1), and the bone morphogenetic protein-6 (BMP6). Furthermore, we presented convincing evidence directly linking reduced miR-122 transcription to inflammation and in chronic liver diseases. The results of this study strongly suggest that prolonged activation of pro-inflammatory signaling pathways, leading to disruption of cytokine-mediated regulation of miR-122, may significantly contribute to the onset and exacerbation of chronic liver disease.
ΔNp63 Regulates Radioresistance in Human Head and Neck Squamous Carcinoma Cells
Authors: Sato Kota , Yoshino Hironori , Sato Yoshiaki , Nakano Manabu , Tsuruga Eichi
Published: July 2023

Radiation therapy is commonly used to treat head and neck squamous cell carcinoma (HNSCC); however, recurrence results from the development of radioresistant cancer cells. Therefore, it is necessary to identify the underlying mechanisms of radioresistance in HNSCC. Previously, we showed that the inhibition of karyopherin-β1 (KPNB1), a factor in the nuclear transport system, enhances radiation-induced cytotoxicity, specifically in HNSCC cells, and decreases the localization of SCC-specific transcription factor ΔNp63. This suggests that ΔNp63 may be a KPNB1-carrying nucleoprotein that regulates radioresistance in HNSCC. Here, we determined whether ΔNp63 is involved in the radioresistance of HNSCC cells. Cell survival was measured by a colony formation assay. Apoptosis was assessed by annexin V staining and cleaved caspase-3 expression. The results indicate that ΔNp63 knockdown decreased the survival of irradiated HNSCC cells, increased radiation-induced annexin V+ cells, and cleaved caspase-3 expression. These results show that ΔNp63 is involved in the radioresistance of HNSCC cells. We further investigated which specific karyopherin-α (KPNA) molecules, partners of KPNB1 for nuclear transport, are involved in nuclear ΔNp63 expression. The analysis of nuclear ΔNp63 protein expression suggests that KPNA1 is involved in nuclear ΔNp63 expression. Taken together, our results suggest that ΔNp63 is a KPNB1-carrying nucleoprotein that regulates radioresistance in HNSCC.
Comparison and Research Progress of Protein Detection Technology for Cultural Relic Materials
Authors: Wu Qian , Zhang Bingjian , Hu Yulan
Published: July 2023

The analysis of historical materials is an essential component of cultural heritage conservation. Protein was one of the most important and pervasive organic substances in ancient human societies. Through the qualitative and quantitative examination of protein-based materials, it is possible to clarify their source and functions of substances in cultural heritages, investigate the manufacturing technology of cultural heritage, and identify their deterioration mechanism. On the basis of these analyses, corresponding measurements are therefore feasible. Currently, mass spectrometry, chromatography, spectroscopy, nuclear magnetic, proteomics, and immunoassay are used to analyse protein materials. Proteomics techniques and enzyme-linked immunosorbent assay (ELISA) technology are two of the most common methods for detecting ancient proteins. This article discusses the evolution of protein component detection in ancient materials, as well as the implementation of proteomics and ELISA techniques for the analysis of proteins. In addition, the characteristics of these two techniques were contrasted in order to propose the most recent analytical techniques and the direction of future research.
Development of Composite Microencapsulated Phase Change Materials for Multi-Temperature Thermal Energy Storage
Authors: Su Weiguang , Darkwa Jo , Zhou Tongyu , Du Dengfeng , Kokogiannakis Georgios , Li Yilin , Wang Li , Gao Liying
Published: July 2023

Phase change energy storage materials have been recognized as potential energy-saving materials for balancing cooling and heating demands in buildings. However, individual phase change materials (PCM) with single phase change temperature cannot be adapted to different temperature requirements. To this end, the concept of fabricating different kinds of microencapsulated PCM (MEPCM) and combing them to form a multiphase change material (MPCM) for multi-seasonal applications in buildings has been proposed. To prove the feasibility of this idea, three kinds of MEPCMs were fabricated and used for the development of three different composite MPCMs, classified as MPCM-1, MPCM-2, and MPCM-3. Analysis of the results shows that each MPCM sample was able to release latent heat at two different temperatures thus making them suitable for multi-temperature thermal energy storage applications. The phase change temperatures of the MPCMs were however found to be slightly reduced by 0.09–0.31 °C as compared with the MEPCMs samples. The measured energy storage capacities for the MPCMs were also reduced in the range of 6.3–11.4% as compared with the theoretical values but they displayed relatively good thermal stability behaviour of up to 197.8–218.8 °C. It was further identified that the phase change temperatures and latent heat of the MPCM was attributed to the weight percentages of individual components, as the theoretical values for the three MPCM samples were all in good accordance with the measured values. Therefore, optimizing the weight ratios of the MEPCM in MPCM samples and their corresponding thermophysical properties based on specific climatic conditions would be a necessary step to take in future investigations. Thermal performance enhancement of the MPCM is also being recommended as an essential part of further research.
Synthesis, Characterization and Structural Analysis of Two New Biguanide Complexes
Authors: Pastrana-Dávila Andrea , Minotta Gianella , Ellena Javier , Santiago Pedro H. O. , D’Vries Richard F.
Published: July 2023

This study reports on the synthesis and characterization of two new coordination compounds of the active pharmaceutical ingredient metformin and transition metals. The cobalt compound with the formula [Co(Met)3][CoCl4]Cl·3H2O is a complex salt formed by a cationic Co(III) octahedral and anionic Co(II) tetrahedral subunits. The Cu(II) complex is represented by the formula [(Cu(Met)Cl)2-μ-Cl2] and is a dimeric compound with two chloride anions acting as a bridge, forming shared-edge square pyramidal units. Both compounds were characterized by single crystal X-ray diffraction, FT-IR spectroscopy and thermal analysis.
Conservation and Ecology of Raptors: Introduction to the Special Issue
Authors: Dobrev Dobromir , Dobrev Vladimir , Demerdzhiev Dimitar
Published: July 2023

Raptors are a diverse avian guild distributed worldwide and adapted to different environments [...]