bluuebunny/crossref_metadata_2025 huggingface dataset:
Time Domain Nonlinear Dynamic Analysis of Vertically Loaded Tapered Pile in Layered Soils
Authors: Shua Qiangqiang , Liu Kexing , Li Jingkai , Tu Wenbo
Published: February 2024

A simplified model is proposed for predicting the nonlinear dynamic response of vertically loaded tapered piles in the time domain, in which the tapered pile is divided into several frustum segments and the four-spring is used for the simulation of the soil–pile interaction. The differential equations for the tapered pile are given and solved by the finite difference method. The vertical dynamic response of a typical tapered pile is investigated, and the consistency of the computational results compared with the finite element results convincingly verifies the reliability of the proposed simplified model. Then, recommended segment numbers, considering the computational efficiency and accuracy requirements for the dynamic analysis of tapered piles, are given. And parametric studies are also carried out to investigate the effect of soil and pile parameters on the nonlinear dynamic response of the tapered pile. The results show that soil nonlinearity significantly affects the vertical dynamic characteristics of the tapered pile. And the tapered pile shows better dynamic characteristics than the cylindrical pile with the same volume and pile length. In addition, the properties of the soil along the upper part of the tapered pile have a more considerable effect on the dynamic response of the tapered pile. These results help to further improve the theory of nonlinear dynamic response analysis of tapered piles and promote its widespread application in engineering practice.
An Analytical Study on the Damage to School Buildings by the 2015 Nepal Earthquake and Damage Level-Based Reconstruction Experience
Authors: Paudyal Youb Raj , Bhandary Netra Prakash
Published: February 2024

The 2015 Nepal Earthquake (Mw7.8) affected more than 9000 schools in the country. Damage distribution in the 14 most-affected administrative districts shows that the construction practices were an important determent for the level of damage extended. The use of improper construction materials, lack of construction supervision, and non-compliance with the existing building codes during design and construction probably contributed to severe damage to most of the school buildings. Based on the damage analysis data and experience of the rebuilding process after the 2015 Nepal Earthquake, this paper highlights the steps to be considered during a rebuilding plan for school buildings after an earthquake disaster. Preliminary damage assessment results show that in the most-affected districts, about 86% of schools (locations) were affected by the earthquake and about one million students were out of their schools for a long time. The damage survey data indicate that about 30% of classrooms collapsed, about 13% of classrooms sustained major damage, and about 17% of classrooms sustained minor damage within the most-affected 14 districts. This damage report is largely based on the secondary data provided by the concerned government authorities. Such evidence of loss and damage in earthquake disasters provides an opportunity to learn lessons for future preparedness and to encounter disaster challenges. This work shares an experience on the rebuilding process of damaged schools and classrooms. It is expected that the experience reported in this paper will help in better planning of the seismic safety of school buildings in Nepal as well as in other similar seismically active regions. Most papers related to the 2015 Nepal Earthquake focus on overall building damage, but this paper addresses the issues of school buildings. As a case report, this paper probably lacks scientific originality, but the presentation of the damage data and the rebuilding process are the original work of the authors.
Physical Activity, Insulin Resistance and Cancer: A Systematic Review
Authors: Navarro-Ledesma Santiago , Hamed-Hamed Dina , González-Muñoz Ana , Pruimboom Leo
Published: February 2024

Introduction: Insulin resistance (IR), a key aspect of type 2 diabetes and a defining characteristic of obesity and its associated conditions, emerges as a mechanistic pathway potentially implicated in cancer pathophysiology. This presents an appealing intervention target for cancer patients. The objective of this study is to conduct a systematic review, examining the scientific evidence regarding the impact of physical activity on modifying insulin resistance in individuals with cancer. Methods: The selection criteria were specific: only randomized controlled clinical trials published in the last 13 years and written in English or Spanish were included. The databases utilized for the search included PubMed, Scopus, Cochrane Library, EBSCO, and WEB OF SCIENCE. The protocol for this review was duly registered in the International Register of Systematic Reviews (CRD42023435002). The final search was conducted on 14 May 2023. Results: The outcomes were assessed using the tool proposed by the Cochrane Handbook to evaluate the risk of bias in the included studies. Among the 12 studies incorporated, 8 demonstrated a low risk of bias, two had an unclear risk of bias, and the remaining two showed a high risk of bias. The variety of exercise types used across all studies was extensive, making definitive conclusions challenging. Physical activity was linked to enhanced insulin sensitivity in seven studies, while five studies showed no significant changes in insulin resistance between the intervention and control groups. Importantly, none of the interventions employed in the included studies exhibited adverse effects on the study participants. Conclusions: The role of exercise as a medicine against insulin resistance has been evidenced in many different studies, mostly related to obesity and cardiovascular diseases. Engaging in physical activity could be a healthy option to combat the effects of insulin resistance in cancer patients, although evidence is weak and limited, according to the results of our systemic review. We further found that literature is lacking at the level of optimal doses, timing, and type of exercise. More studies are needed with more defined PA programs in type and length.
Comment on Wu et al. Baveno VII Criteria Is an Accurate Risk Stratification Tool to Predict High-Risk Varices Requiring Intervention and Hepatic Events in Patients with Advanced Hepatocellular Carcinoma. Cancers 2023, 15, 2480
Authors: Allaire Manon , Thabut Dominique
Published: February 2024

We read with great interest the original research conducted by Wu et al [...]
Management of Hepatocellular Carcinoma in 2024: The Multidisciplinary Paradigm in an Evolving Treatment Landscape
Authors: Kinsey Emily , Lee Hannah M.
Published: February 2024

Liver cancer is the third most common cause of cancer-related deaths worldwide, and hepatocellular carcinoma (HCC) makes up the majority of liver cancer cases. Despite the stabilization of incidence rates in recent years due to effective viral hepatitis treatments, as well as improved outcomes from early detection and treatment advances, the burden of HCC is anticipated to rise again due to increasing rates of metabolic dysfunction-associated steatotic liver disease and alcohol-related liver disease. The treatment landscape is evolving and requires a multidisciplinary approach, often involving multi-modal treatments that include surgical resection, transplantation, local regional therapies, and systemic treatments. The optimal approach to the care of the HCC patient requires a multidisciplinary team involving hepatology, medical oncology, diagnostic and interventional radiology, radiation oncology, and surgery. In order to determine which approach is best, an individualized treatment plan should consider the patient’s liver function, functional status, comorbidities, cancer stage, and preferences. In this review, we provide an overview of the current treatment options and key trials that have revolutionized the management of HCC. We also discuss evolving treatment paradigms for the future.
Efficacy and Mechanism of Hypofractionation Radiotherapy Combined with PD-1 Inhibitors in a Model of Head and Neck Melanoma
Authors: Yin Gaofei , Guo Wei , Chen Xiaohong , Zhang Yang , Huang Zhigang
Published: February 2024

Head and neck mucosal melanoma is one of the most common types of melanoma in China, but the prognosis is worse than other types, and there is no effective treatment plan to improve patient survival. This study analyzes the efficacy of hypofractionation radiotherapy combined with PD-1 inhibitor in the treatment of head and neck mucosal melanoma, as well as its impact on the tumor immune microenvironment. NPSG mice were used to construct a humanized bilateral lesion tumor model of the humanized immune system. The models were divided into an RT (8 Gy)+anti PD-1 group, an RT (2 GyX4)+anti PD-1 group, an Anti PD-1 group, an RT (8 Gy) group, and a blank group. Differences in efficacy and immune cells in blood, lymph nodes, and tumor tissues were compared between different treatment groups. The treatment effect of RT (8 Gy)+anti PD-1 was better than the other groups with a tumor growth inhibition value (TGI) over 60%. Significant recruitment and activation of CD8+T cells were found in the blood, lymph nodes, and tumor tissues and significantly inhibited the level of PD-1+CD8+T cells in the group of RT (8 Gy)+anti PD-1. This study confirmed the efficacy of hypofractionation radiotherapy combined with PD-1 inhibitors, which can inhibit tumor growth and produce distant effects. The appearance of a distant effect is related to the enhancement in the number and activity of CD8+T cells in the local tumor and peripheral blood and lymph nodes. This study confirms the therapeutic and immune regulatory effect of hypofractionation radiotherapy combined with PD-1 inhibitors.
Macrophages Promote Subtype Conversion and Endocrine Resistance in Breast Cancer
Authors: Zhang Xiaoyan , Yang Fengyu , Huang Zhijian , Liu Xiaojun , Xia Gan , Huang Jieye , Yang Yang , Li Junchen , Huang Jin , Liu Yuxin , Zhou Ti , Qi Weiwei , Gao Guoquan , Yang Xia
Published: February 2024

Background: The progression of tumors from less aggressive subtypes to more aggressive states during metastasis poses challenges for treatment strategies. Previous studies have revealed the molecular subtype conversion between primary and metastatic tumors in breast cancer (BC). However, the subtype conversion during lymph node metastasis (LNM) and the underlying mechanism remains unclear. Methods: We compared clinical subtypes in paired primary tumors and positive lymph nodes (PLNs) in BC patients and further validated them in the mouse model. Bioinformatics analysis and macrophage-conditioned medium treatment were performed to investigate the role of macrophages in subtype conversion. Results: During LNM, hormone receptors (HRs) were down-regulated, while HER2 was up-regulated, leading to the transformation of luminal A tumors towards luminal B tumors and from luminal B subtype towards HER2-enriched (HER2-E) subtype. The mouse model demonstrated the elevated levels of HER2 in PLN while retaining luminal characteristics. Among the various cells in the tumor microenvironment (TME), macrophages were the most clinically relevant in terms of prognosis. The treatment of a macrophage-conditioned medium further confirmed the downregulation of HR expression and upregulation of HER2 expression, inducing tamoxifen resistance. Through bioinformatics analysis, MNX1 was identified as a potential transcription factor governing the expression of HR and HER2. Conclusion: Our study revealed the HER2-E subtype conversion during LNM in BC. Macrophages were the crucial cell type in TME, inducing the downregulation of HR and upregulation of HER2, probably via MNX1. Targeting macrophages or MNX1 may provide new avenues for endocrine therapy and targeted treatment of BC patients with LNM.
Claudin 18.2 as a New Biomarker in Gastric Cancer—What Should We Know?
Authors: Mathias-Machado Maria Cecília , de Jesus Victor Hugo Fonseca , Jácome Alexandre , Donadio Mauro Daniel , Aruquipa Marcelo Porfirio Sunagua , Fogacci João , Cunha Renato Guerino , da Silva Leonard Medeiros , Peixoto Renata D’Alpino
Published: February 2024

Gastric cancer (GC) remains a formidable global health challenge, ranking among the top-five causes of cancer-related deaths worldwide. The majority of patients face advanced stages at diagnosis, with a mere 6% five-year survival rate. First-line treatment for metastatic GC typically involves a fluoropyrimidine and platinum agent combination; yet, predictive molecular markers have proven elusive. This review navigates the evolving landscape of GC biomarkers, with a specific focus on Claudin 18.2 (CLDN18.2) as an emerging and promising target. Recent phase III trials have unveiled the efficacy of Zolbetuximab, a CLDN18.2-targeting antibody, in combination with oxaliplatin-based chemotherapy for CLDN18.2-positive metastatic GC. As this novel therapeutic avenue unfolds, understanding the nuanced decision making regarding the selection of anti-CLDN18.2 therapies over other targeted agents in metastatic GC becomes crucial. This manuscript reviews the evolving role of CLDN18.2 as a biomarker in GC and explores the current status of CLDN18.2-targeting agents in clinical development. The aim is to provide concise insights into the potential of CLDN18.2 as a therapeutic target and guide future clinical decisions in the management of metastatic GC.
Understanding Cancer’s Defense against Topoisomerase-Active Drugs: A Comprehensive Review
Authors: Sharma Nilesh Kumar , Bahot Anjali , Sekar Gopinath , Bansode Mahima , Khunteta Kratika , Sonar Priyanka Vijay , Hebale Ameya , Salokhe Vaishnavi , Sinha Birandra Kumar
Published: February 2024

In recent years, the emergence of cancer drug resistance has been one of the crucial tumor hallmarks that are supported by the level of genetic heterogeneity and complexities at cellular levels. Oxidative stress, immune evasion, metabolic reprogramming, overexpression of ABC transporters, and stemness are among the several key contributing molecular and cellular response mechanisms. Topo-active drugs, e.g., doxorubicin and topotecan, are clinically active and are utilized extensively against a wide variety of human tumors and often result in the development of resistance and failure to therapy. Thus, there is an urgent need for an incremental and comprehensive understanding of mechanisms of cancer drug resistance specifically in the context of topo-active drugs. This review delves into the intricate mechanistic aspects of these intracellular and extracellular topo-active drug resistance mechanisms and explores the use of potential combinatorial approaches by utilizing various topo-active drugs and inhibitors of pathways involved in drug resistance. We believe that this review will help guide basic scientists, pre-clinicians, clinicians, and policymakers toward holistic and interdisciplinary strategies that transcend resistance, renewing optimism in the ongoing battle against cancer.
Intraoperative Flow Cytometry for the Rapid Diagnosis and Validation of Surgical Clearance of Non-Melanoma Skin Cancer: A Prospective Clinical Feasibility Study
Authors: Markopoulos Georgios , Lampri Evangeli , Tragani Ioulia , Kourkoumelis Nikolaos , Vartholomatos Georgios , Seretis Konstantinos
Published: February 2024

Non-melanoma skin cancer (NMSC) is the most prevalent cancer in humans, with a high global incidence. We present a prospective clinical feasibility study on the use of intraoperative flow cytometry (iFC) for the instant diagnosis of NMSC and its complete surgical clearance. Flow cytometry, a laser-based technique, quantifies cell features, which has applications in cancer research. This study aim is to explore the potential applicability of iFC in detecting and characterizing NMSC and its surgical margins. In total, 30 patients who underwent diagnosis for NMSC were recruited. The method demonstrated high sensitivity (95.2%) and specificity (87.1%), with an accuracy of 91.1%, as confirmed with a receiver operating characteristic curve analysis. The results also indicated that most tumors were diploid, with two cases being hypoploid. The average G0/G1 fractions for normal and tumor tissue samples were 96.03 ± 0.30% and 88.03 ± 1.29%, respectively, with the tumor index escalating from 3.89 ± 0.30% to 11.95 ± 1.29% in cancerous cells. These findings underscore iFC’s capability for precise intraoperative NMSC characterization and margin evaluation, promising enhanced complete tumor excision rates. Given the technique’s successful application in various other malignancies, its implementation in NMSC diagnosis and treatment holds significant promise and warrants further research in clinical trials.
Scalp Irradiation with 3D-Milled Bolus: Initial Dosimetric and Clinical Experience
Authors: Dibs Khaled , Gogineni Emile , Jhawar Sachin M. , Baliga Sujith , Grecula John C. , Mitchell Darrion L. , Palmer Joshua , Haglund Karl , Andraos Therese Youssef , Zoller Wesley , Ewing Ashlee , Bonomi Marcelo , Bhateja Priyanka , Tinoco Gabriel , Liebner David , Rocco James W. , Old Matthew , Gamez Mauricio E. , Chakravarti Arnab , Konieczkowski David J. , Blakaj Dukagjin M.
Published: February 2024

Background and purpose: A bolus is required when treating scalp lesions with photon radiation therapy. Traditional bolus materials face several issues, including air gaps and setup difficulty due to irregular, convex scalp geometry. A 3D-milled bolus is custom-formed to match individual patient anatomy, allowing improved dose coverage and homogeneity. Here, we describe the creation process of a 3D-milled bolus and report the outcomes for patients with scalp malignancies treated with Volumetric Modulated Arc Therapy (VMAT) utilizing a 3D-milled bolus. Materials and methods: Twenty-two patients treated from 2016 to 2022 using a 3D-milled bolus and VMAT were included. Histologies included squamous cell carcinoma (n = 14, 64%) and angiosarcoma (n = 8, 36%). A total of 7 (32%) patients were treated in the intact and 15 (68%) in the postoperative setting. The median prescription dose was 66.0 Gy (range: 60.0–69.96). Results: The target included the entire scalp for 8 (36%) patients; in the remaining 14 (64%), the median ratio of planning target volume to scalp volume was 35% (range: 25–90%). The median dose homogeneity index was 1.07 (range: 1.03–1.15). Six (27%) patients experienced acute grade 3 dermatitis and one (5%) patient experienced late grade 3 skin ulceration. With a median follow-up of 21.4 months (range: 4.0–75.4), the 18-month rates of locoregional control and overall survival were 75% and 79%, respectively. Conclusions: To our knowledge, this is the first study to report the clinical outcomes for patients with scalp malignancies treated with the combination of VMAT and a 3D-milled bolus. This technique resulted in favorable clinical outcomes and an acceptable toxicity profile in comparison with historic controls and warrants further investigation in a larger prospective study.
AI-Based Detection of Oral Squamous Cell Carcinoma with Raman Histology
Authors: Weber Andreas , Enderle-Ammour Kathrin , Kurowski Konrad , Metzger Marc C. , Poxleitner Philipp , Werner Martin , Rothweiler René , Beck Jürgen , Straehle Jakob , Schmelzeisen Rainer , Steybe David , Bronsert Peter
Published: February 2024

Stimulated Raman Histology (SRH) employs the stimulated Raman scattering (SRS) of photons at biomolecules in tissue samples to generate histological images. Subsequent pathological analysis allows for an intraoperative evaluation without the need for sectioning and staining. The objective of this study was to investigate a deep learning-based classification of oral squamous cell carcinoma (OSCC) and the sub-classification of non-malignant tissue types, as well as to compare the performances of the classifier between SRS and SRH images. Raman shifts were measured at wavenumbers k1 = 2845 cm−1 and k2 = 2930 cm−1. SRS images were transformed into SRH images resembling traditional H&E-stained frozen sections. The annotation of 6 tissue types was performed on images obtained from 80 tissue samples from eight OSCC patients. A VGG19-based convolutional neural network was then trained on 64 SRS images (and corresponding SRH images) and tested on 16. A balanced accuracy of 0.90 (0.87 for SRH images) and F1-scores of 0.91 (0.91 for SRH) for stroma, 0.98 (0.96 for SRH) for adipose tissue, 0.90 (0.87 for SRH) for squamous epithelium, 0.92 (0.76 for SRH) for muscle, 0.87 (0.90 for SRH) for glandular tissue, and 0.88 (0.87 for SRH) for tumor were achieved. The results of this study demonstrate the suitability of deep learning for the intraoperative identification of tissue types directly on SRS and SRH images.
Integrated Analysis of Single-Cell and Bulk RNA Sequencing Data Reveals Memory-like NK Cell Subset Associated with Mycobacterium tuberculosis Latency
Authors: Shekarkar Azgomi Mojtaba , Badami Giusto Davide , Lo Pizzo Marianna , Tamburini Bartolo , Dieli Costanza , La Manna Marco Pio , Dieli Francesco , Caccamo Nadia
Published: February 2024

Natural killer (NK) cells are innate-like lymphocytes that belong to the family of type-1 innate lymphoid cells and rapidly respond to virus-infected and tumor cells. In this study, we have combined scRNA-seq data and bulk RNA-seq data to define the phenotypic and molecular characteristics of peripheral blood NK cells. While the role of NK cells in immune surveillance against virus infections and tumors has been well established, their contribution to protective responses to other intracellular microorganisms, such as Mycobacterium tuberculosis (Mtb), is still poorly understood. In this study, we have combined scRNA-seq data and bulk RNA-seq data to illuminate the molecular characteristics of circulating NK cells in patients with active tuberculosis (TB) disease and subjects with latent Mtb infection (LTBI) and compared these characteristics with those of healthy donors (HDs) and patients with non-TB other pulmonary infectious diseases (ODs). We show here that the NK cell cluster was significantly increased in LTBI subjects, as compared to patients with active TB or other non-TB pulmonary diseases and HD, and this was mostly attributable to the expansion of an NK cell population expressing KLRC2, CD52, CCL5 and HLA-DRB1, which most likely corresponds to memory-like NK2.1 cells. These data were validated by flow cytometry analysis in a small cohort of samples, showing that LTBI subjects have a significant expansion of NK cells characterized by the prevalence of memory-like CD52+ NKG2C+ NK cells. Altogether, our results provide some new information on the role of NK cells in protective immune responses to Mtb.
Levels of Circulating Ketone Bodies in Patients Undergoing Cardiac Surgery on Cardiopulmonary Bypass
Authors: Levis Anja , Huber Markus , Mathis Déborah , Filipovic Mark G. , Stieger Andrea , Räber Lorenz , Stueber Frank , Luedi Markus M.
Published: February 2024

Ketone bodies (KBs) are energy-efficient substrates utilized by the heart depending on its metabolic demand and substrate availability. Levels of circulating KBs have been shown to be elevated in acute and chronic cardiovascular disease and are associated with severity of disease in patients with heart failure and functional outcome after myocardial infarction. To investigate whether this pattern similarly applies to patients undergoing cardiac surgery involving cardiopulmonary bypass (CPB), we analysed prospectively collected pre- and postoperative blood samples from 192 cardiac surgery patients and compared levels and perioperative changes in total KBs with Troponin T as a marker of myocardial cell injury. We explored the association of patient characteristics and comorbidities for each of the two biomarkers separately and comparatively. Median levels of KBs decreased significantly over the perioperative period and inversely correlated with changes observed for Troponin T. Associations of patient characteristics with ketone body perioperative course showed notable differences compared to Troponin T, possibly highlighting factors acting as a “driver” for the change in the respective biomarker. We found an inverse correlation between perioperative change in ketone body levels and changes in troponin, indicating a marked decrease in ketone body concentrations in patients exhibiting greater myocardial cell injury. Further investigations aimed at better understanding the role of KBs on perioperative changes are warranted.
Vasoactive Intestinal Peptide Receptor, CRTH2, Antagonist Treatment Improves Eosinophil and Mast Cell-Mediated Esophageal Remodeling and Motility Dysfunction in Eosinophilic Esophagitis
Authors: Yadavalli Chandra Sekhar , Upparahalli Venkateshaiah Sathisha , Verma Alok K. , Kathera Chandrasekhar , Duncan Pearce S. , Vaezi Michael , Paul Richard J. , Mishra Anil
Published: February 2024

Background and Aims: Ultrasonography has shown that eosinophils accumulate in each segment of the esophageal mucosa in human EoE, ultimately promoting esophageal motility dysfunction; however, no mechanistic evidence explains how or why this accumulation occurs. Methods: Quantitative PCR, ELISA, flow cytometry, immunostaining, and immunofluorescence analyses were performed using antibodies specific to the related antigens and receptors. Results: In deep esophageal biopsies of EoE patients, eosinophils and mast cells accumulate adjacent to nerve cell-derived VIP in each esophageal segment. qRT-PCR analysis revealed five- to sixfold increases in expression levels of VIP, CRTH2, and VAPC2 receptors and proteins in human blood- and tissue-accumulated eosinophils and mast cells. We also observed a significant correlation between mRNA CRTH2 levels and eosinophil- and nerve cell-derived VIPs in human EoE (p < 0.05). We provide evidence that eosinophil and mast cell deficiency following CRTH2 antagonist treatment improves motility dysfunction in a chronic DOX-inducible CC10-IL-13 murine model of experimental EoE. Conclusions: CRTH2 antagonist treatment is a novel therapeutic strategy for inflammatory cell-induced esophageal motility dysfunction in IL-13-induced chronic experimental EoE.
Cell-Free DNA 5-Hydroxymethylcytosine Signatures for Lung Cancer Prognosis
Authors: Shao Jianming , Olsen Randall J. , Kasparian Saro , He Chuan , Bernicker Eric H. , Li Zejuan
Published: February 2024

Accurate prognostic markers are essential for guiding effective lung cancer treatment strategies. The level of 5-hydroxymethylcytosine (5hmC) in tissue is independently associated with overall survival (OS) in lung cancer patients. We explored the prognostic value of cell-free DNA (cfDNA) 5hmC through genome-wide analysis of 5hmC in plasma samples from 97 lung cancer patients. In both training and validation sets, we discovered a cfDNA 5hmC signature significantly associated with OS in lung cancer patients. We built a 5hmC prognostic model and calculated the weighted predictive scores (wp-score) for each sample. Low wp-scores were significantly associated with longer OS compared to high wp-scores in the training [median 22.9 versus 8.2 months; p = 1.30 × 10−10; hazard ratio (HR) 0.04; 95% confidence interval (CI), 0.00–0.16] and validation (median 18.8 versus 5.2 months; p = 0.00059; HR 0.22; 95% CI: 0.09–0.57) sets. The 5hmC signature independently predicted prognosis and outperformed age, sex, smoking, and TNM stage for predicting lung cancer outcomes. Our findings reveal critical genes and signaling pathways with aberrant 5hmC levels, enhancing our understanding of lung cancer pathophysiology. The study underscores the potential of cfDNA 5hmC as a superior prognostic tool for guiding more personalized therapeutic strategies for lung cancer patients.
Molecular Characterization and Subtyping of Breast Cancer Cell Lines Provide Novel Insights into Cancer Relevant Genes
Authors: Pommerenke Claudia , Nagel Stefan , Haake Josephine , Koelz Anne Leena , Christgen Matthias , Steenpass Laura , Eberth Sonja
Published: February 2024

Continuous cell lines are important and commonly used in vitro models in breast cancer (BC) research. Selection of the appropriate model cell line is crucial and requires consideration of their molecular characteristics. To characterize BC cell line models in depth, we profiled a panel of 29 authenticated and publicly available BC cell lines by mRNA-sequencing, mutation analysis, and immunoblotting. Gene expression profiles separated BC cell lines in two major clusters that represent basal-like (mainly triple-negative BC) and luminal BC subtypes, respectively. HER2-positive cell lines were located within the luminal cluster. Mutation calling highlighted the frequent aberration of TP53 and BRCA2 in BC cell lines, which, therefore, share relevant characteristics with primary BC. Furthermore, we showed that the data can be used to find novel, potential oncogenic fusion transcripts, e.g., FGFR2::CRYBG1 and RTN4IP1::CRYBG1 in cell line MFM-223, and to elucidate the regulatory circuit of IRX genes and KLF15 as novel candidate tumor suppressor genes in BC. Our data indicated that KLF15 was activated by IRX1 and inhibited by IRX3. Moreover, KLF15 inhibited IRX1 in cell line HCC-1599. Each BC cell line carries unique molecular features. Therefore, the molecular characteristics of BC cell lines described here might serve as a valuable resource to improve the selection of appropriate models for BC research.
Different Impacts of DNA-PK and mTOR Kinase Inhibitors in Combination with Ionizing Radiation on HNSCC and Normal Tissue Cells
Authors: Klieber Nina , Hildebrand Laura S. , Faulhaber Eva , Symank Julia , Häck Nicole , Härtl Annamaria , Fietkau Rainer , Distel Luitpold V.
Published: February 2024

Despite substantial advancements in understanding the pathomechanisms of head and neck squamous cell carcinoma (HNSCC), effective therapy remains challenging. The application of kinase inhibitors (KIs) in HNSCC, specifically mTOR and DNA-PK inhibitors, can increase radiosensitivity and therefore presents a promising strategy when used simultaneously with ionizing radiation (IR) in cancer treatment. Our study focused on the selective DNA-PK-inhibitor AZD7648; the selective mTOR-inhibitor Sapanisertib; and CC-115, a dual inhibitor targeting both mTOR and DNA-PK. The impact of these KIs on HNSCC and normal tissue cells was assessed using various analytical methods including cell death studies, cell cycle analysis, real-time microscopy, colony-forming assays and immunohistochemical staining for γH2AX and downstream mTOR protein p-S6. We detected a strong inhibition of IR-induced DNA double-strand break (DSB) repair, particularly in AZD7648-treated HNSCC, whereas normal tissue cells repaired DNA DSB more efficiently. Additionally, AZD7648 + IR treatment showed a synergistic decline in cell proliferation and clonogenicity, along with an elevated G2/M arrest and cell death in the majority of HNSCC cell lines. CC-115 + IR treatment led to an elevation in G2/M arrest, increased cell death, and a synergistic reduction in cell proliferation, though the effect was notably lower compared to the AZD7648 + IR- treated group. Sapanisertib led to a high cellular toxicity in both HNSCC and normal tissue cells, even in non-irradiated cells. Regarding cell proliferation and the induction of apoptosis and necrosis, Sapanisertib + IR was beneficial only in HPV+ HNSCC. Overall, this study highlights the potential of AZD7648 as a radiosensitizing agent in advanced-stage HPV-positive and negative HNSCC, offering a promising therapeutic strategy. However, the dual mTOR/DNA-PK-I CC-115 did not provide a distinct advantage over the use of selective KIs in our investigations, suggesting limited benefits for its application in KI + IR therapy. Notably, the selective mTOR-inhibitor Sapanisertib was only beneficial in HPV+ HNSCC and should not be applied in HPV− cases.
Coconut-Solid-Waste-Derived Hard-Carbon Anode Materials for Fast Potassium Ion Storage
Authors: Ma Yi , Liu Wenhao , Liu Wenhan , Zhang Guangwan , Wang Yu , Wang Haokai , Chen Wei , Huang Meng , Wang Xuanpeng
Published: February 2024

Hard carbon, which features recyclability, low costs, and environmental friendliness, is an attractive anode material for K+ storage. Nevertheless, the state-of-the-art hard carbon is still unsatisfactory due to its poor multiplication performance and unclear energy storage mechanism. In this study, a one-pot carbonisation method using coconut solid waste biomass is applied to obtain high-performance hard-carbon (CHC) anode materials. The microstructure and electrochemical properties of the CHC are investigated at different carbonisation temperatures (1100–1500 °C). The CHC materials prepared at 1300 °C (CHC1300) have a high capacity of 265.8 mAh g−1 at a current density of 25 mA g−1 and a superior cyclability of 1000 cycles at 1.0 A g−1 with a capacity retention of 96.6%. This approach, referred to as the “biomass-to-application” strategy, holds promise for advancing the development of cost-effective and sustainable KIBs.
The Wavelet Transform for Feature Extraction and Surface Roughness Evaluation after Micromachining
Authors: Grochała Daniel , Grzejda Rafał , Parus Arkadiusz , Berczyński Stefan
Published: February 2024

Miniaturization is a dominant trend in machine building which requires the use of advanced techniques of manufacturing and control. Apart from dimensional and shape precision of miniaturized components, surface geometry, particularly roughness and so-called microroughness that results from the use of advanced treatment techniques, plays an important role in correct assembly, reliable operation and durability of the whole machine. The selection of filtration method in surface geometry of micro-objects can be a substantial problem. The authors of the paper propose to use wavelet filtration in digital processing of a point cloud to remove measurement noise and not to change the surface character of the measured object. Also, the authors propose, in this paper, some criteria for selecting the number of wavelet filtration levels based on minimalization of the RMS value. It is supposed to improve the efficiency of low-pass filtration of small areas of the surface, particularly compared to traditional λs Gaussian filtration.
Microstructure, Hardness and Corrosion Resistance of Al-TiC MMC Prepared by Laser Cladding on AZ31B Magnesium Alloy
Authors: Pi Haiwen , Zhi Geng , Chen Canyang , Li Chen , Zhou Jun , Long Yu
Published: February 2024

Magnesium alloy is extensively used in aircraft, automobiles, and electronic industries due to its low density, high specific strength, and enhanced machinability. However, low hardness and poor corrosion resistance limit its application. In this work, an Al-TiC metal matrix composite (MMC) was prepared on AZ31B magnesium alloy via laser cladding. The effects of laser power and TiC content on the microstructure, hardness, and corrosion resistance of the MMC were investigated. The results showed that the MMC with 10% TiC had a hardness of 184 HV0.1, which was 3.5 times higher than 52 HV0.1 of the substrate. The current density of MMC with 10% TiC was 3.90 × 10−7 A/cm2, which was three orders of magnitude lower than 5.45 × 10−4 A/cm2 of the substrate. Due to more intermetallic compounds (IMCs) and TiC particles, the MMC with 30% TiC had higher hardness. The increased laser power would not change the phase composition, but it contributed to the formation of a concave crescent shape, promoted the diffusion of Mg, and induced the formation of a thicker Al3Mg2 transition layer. Modifications in the TiC concentration markedly influenced the coating’s microstructural characteristics.
Organic Patinas on Small Historical Bronzes: From Mock-Ups to Actual Artworks
Authors: Galeotti Monica , Porcinai Simone , Cagnini Andrea , Baruffetti Maria , Biondi Caterina , Dal Fovo Alice , Fontana Raffaella
Published: February 2024

This paper deals with the study of organic coatings (patinas) on historical bronzes, specifically those applied on small-size statues in Renaissance workshops. These coatings, often transparent and translucent, contain a mixture of organic and inorganic components and may be still preserved in hidden parts of statues in indoor displays. However, the complexity of the original varnishes, their degradation and alteration over time, and the coexistence of materials added for conservation and maintenance purposes are challenging for their characterization. The often well-preserved surface of varnished bronzes and their small size make it mandatory to make the most of using noninvasive techniques for their investigation. To this end, to simulate the actual historical coatings, we prepared a set of mock-ups following ancient recipes and using materials that were available in the Renaissance. We used the samples to assess to what extent it is possible to disclose the formulation (binders, colourants, and other additives) and the thickness of a Renaissance patina with noninvasive methods. Microprofilometry (MP), optical coherence tomography (OCT), and eddy current (EC) gauge were tested on the samples and the results were combined with reflectance Fourier transform infrared (FT-IR) spectroscopy. The analyses performed on the mock-ups set the ground for investigating a Renaissance bronze featuring reddish semi-transparent varnish layers. The achievements are discussed in this paper, along with the limitations of the use of a noninvasive approach.
Hemostasis in Pre-Eclamptic Women and Their Offspring: Current Knowledge and Hemostasis Assessment with Viscoelastic Tests
Authors: Kontovazainitis Christos-Georgios , Gialamprinou Dimitra , Theodoridis Theodoros , Mitsiakos Georgios
Published: February 2024

Pre-eclampsia (PE) is a placenta-mediated disease and remains a major cause of maternal and neonatal mortality and morbidity. As PE develops, normal pregnancy’s hypercoagulable balance is disrupted, leading to platelet hyperactivation, excessive pathological hypercoagulability, and perturbed fibrinolysis. This narrative review aims to summarize the current knowledge regarding hemostasis in PE compared with healthy gestation and the potential effects of maternal PE on neonatal hemostasis. Finally, it aims to discuss hemostasis assessments for normal pregnancies and PE, emphasizing the role of viscoelastic tests, namely, thromboelastography (TEG) and thromboelastometry (ROTEM), for monitoring PE-associated hemostatic alterations. The use of TEG/ROTEM for assessing the hemostatic profile of PE women has been little considered, even though conventional coagulation tests (CCTs) have not helped to monitor hemostasis in this population. Compared with normal pregnancy, TEG/ROTEM in PE reveals an excessive hypercoagulability analogous with the severity of the disease, characterized by higher-stability fibrin clots. The TEG/ROTEM parameters can reflect PE severity and may be used for monitoring and as predictive markers for the disease.
A Survey on Challenges and Advances in Natural Language Processing with a Focus on Legal Informatics and Low-Resource Languages
Authors: Krasadakis Panteleimon , Sakkopoulos Evangelos , Verykios Vassilios S.
Published: February 2024

The field of Natural Language Processing (NLP) has experienced significant growth in recent years, largely due to advancements in Deep Learning technology and especially Large Language Models. These improvements have allowed for the development of new models and architectures that have been successfully applied in various real-world applications. Despite this progress, the field of Legal Informatics has been slow to adopt these techniques. In this study, we conducted an extensive literature review of NLP research focused on legislative documents. We present the current state-of-the-art NLP tasks related to Law Consolidation, highlighting the challenges that arise in low-resource languages. Our goal is to outline the difficulties faced by this field and the methods that have been developed to overcome them. Finally, we provide examples of NLP implementations in the legal domain and discuss potential future directions.
A Survey on Video Streaming for Next-Generation Vehicular Networks
Authors: Huang Chenn-Jung , Cheng Hao-Wen , Lien Yi-Hung , Jian Mei-En
Published: February 2024

As assisted driving technology advances and vehicle entertainment systems rapidly develop, future vehicles will become mobile cinemas, where passengers can use various multimedia applications in the car. In recent years, the progress in multimedia technology has given rise to immersive video experiences. In addition to conventional 2D videos, 360° videos are gaining popularity, and volumetric videos, which can offer users a better immersive experience, have been discussed. However, these applications place high demands on network capabilities, leading to a dependence on next-generation wireless communication technology to address network bottlenecks. Therefore, this study provides an exhaustive overview of the latest advancements in video streaming over vehicular networks. First, we introduce related work and background knowledge, and provide an overview of recent developments in vehicular networking and video types. Next, we detail various video processing technologies, including the latest released standards. Detailed explanations are provided for network strategies and wireless communication technologies that can optimize video transmission in vehicular networks, paying special attention to the relevant literature regarding the current development of 6G technology that is applied to vehicle communication. Finally, we proposed future research directions and challenges. Building upon the technologies introduced in this paper and considering diverse applications, we suggest a suitable vehicular network architecture for next-generation video transmission.
Research on an Enhanced Multimodal Network for Specific Emitter Identification
Authors: Peng Heli , Xie Kai , Zou Wenxu
Published: February 2024

Specific emitter identification (SEI) refers to the task of distinguishing similar emitters, especially those of the same type and transmission parameters, which is one of the most critical tasks of electronic warfare. However, SEI is still a challenging task when a feature has low physical representation. Feature representation largely determines the recognition results. Therefore, this article expects to move toward robust feature representation for SEI. Efficient multimodal strategies have great potential for applications using multimodal data and can further improve the performance of SEI. In this research, we introduce a multimodal emitter identification method that explores the application of multimodal data, time-series radar signals, and feature vector data to an enhanced transformer, which employs a conformer block to embed the raw data and integrates an efficient multimodal feature representation module. Moreover, we employ self-knowledge distillation to mitigate overconfident predictions and reduce intra-class variations. Our study reveals that multimodal data provide sufficient information for specific emitter identification. Simultaneously, we propose the CV-CutMixOut method to augment the time-domain signal. Extensive experiments on real radar datasets indicate that the proposed method achieves more accurate identification results and higher feature discriminability.
Hyperbolic-Embedding-Aided Geographic Routing in Intelligent Vehicular Networks
Authors: Pan Ying , Lyu Na
Published: February 2024

Intelligent vehicular networks can not only connect various smart terminals to manned or unmanned vehicles but also to roads and people’s hands. In order to support diverse vehicle-to-everything (V2X) applications in dynamic, intelligent vehicular networks, efficient and flexible routing is fundamental but challenging. Aimed to eliminate routing voids in traditional Euclidean geographic greedy routing strategies, we propose a hyperbolic-embedding-aided geographic routing strategy (HGR) in this paper. By embedding the network topology into a two-dimensional Poincaré hyperbolic disk, greedy forwarding is performed according to nodes’ hyperbolic coordinates. Simulation results demonstrated that the proposed HGR strategy can greatly enhance the routing success rate through a smaller stretch of the routing paths, with little sacrifice of routing computation time.
Hybrid Uncertainty Calibration for Multimodal Sentiment Analysis
Authors: Pan Qiuyu , Meng Zuqiang
Published: February 2024

In open environments, multimodal sentiment analysis (MSA) often suffers from low-quality data and can be disrupted by noise, inherent defects, and outliers. In some cases, unreasonable multimodal fusion methods can perform worse than unimodal methods. Another challenge of MSA is effectively enabling the model to provide accurate prediction when it is confident and to indicate high uncertainty when its prediction is likely to be inaccurate. In this paper, we propose an uncertain-aware late fusion based on hybrid uncertainty calibration (ULF-HUC). Firstly, we conduct in-depth research on the issue of sentiment polarity distribution in MSA datasets, establishing a foundation for an uncertain-aware late fusion method, which facilitates organic fusion of modalities. Then, we propose a hybrid uncertainty calibration method based on evidential deep learning (EDL) that balances accuracy and uncertainty, supporting the reduction of uncertainty in each modality of the model. Finally, we add two common types of noise to validate the effectiveness of our proposed method. We evaluate our model on three publicly available MSA datasets (MVSA-Single, MVSA-Multiple, and MVSA-Single-Small). Our method outperforms state-of-the-art approaches in terms of accuracy, weighted F1 score, and expected uncertainty calibration error (UCE) metrics, proving the effectiveness of the proposed method.
A Test System for Transmission Expansion Planning Studies
Authors: Dhamala Bhuban , Ghassemi Mona
Published: February 2024

This paper introduces a 17-bus 500 kV test system intended for transmission expansion planning (TEP) studies. The overhead lines used in the system are based on an actual 500 kV transmission line geometry. Although several test systems have been developed for various forms of power system analysis, few are specifically tailored for TEP studies at the transmission voltage level, as opposed to the distribution voltage level. Current test systems for TEP studies are limited to single loading conditions only for normal operating conditions, and the majority of these systems are intertwined with issues related to the energy market or devised specifically for integrating new generations and loads into the existing power systems. However, ensuring a test system satisfies both voltage drop and line loading criteria during both normal and all single contingency operations is crucial in TEP studies, and addressing these issues under contingency conditions poses notable challenges. Moreover, practical TEP scenarios involve varied loadings, including peak load and dominant loading (60% of peak load) scenarios, while the existing test systems are configured solely for single loading conditions. To address these technical gaps, this paper introduces the 17-bus test system operating at a transmission voltage level of 500 kV, meeting technical requirements under normal and all single contingency operations for both peak load and dominant load scenarios. Detailed specifications of the proposed test system and load flow analysis at both normal and contingency conditions for different loading conditions are presented. This test system serves as an invaluable resource for TEP studies.