bluuebunny/crossref_metadata_2025 huggingface dataset:
A Comprehensive Overview of Micro-Influencer Marketing: Decoding the Current Landscape, Impacts, and Trends
Authors: Chen Jie , Zhang Yangting , Cai Han , Liu Lu , Liao Miyan , Fang Jiaming
Published: March 2024

This research provides a comprehensive overview of micro-influence marketing, analyzing the characteristics of influencers and the mechanisms of their impact. A systematic review was conducted, encompassing 2091 citing articles and references across 74 studies involving 95 research institutions and over 12,000 samples. Employing an interdisciplinary approach that integrates insights from computer science, information science, communication, culture, psychology, sociology, education, business, and management, this study outlines the distinct features of micro-influencers. These features include performable authenticity, affinity expressed through consistency and transparency, musical and artistic media talent, and competitive individual traits. The research synthesizes antecedents of trust and attachment mechanisms commonly employed in influencer theory, taking an objective standpoint and minimizing emphasis on audience engagement and perception to trigger influence. The findings highlight that followers’ pursuit of self-branding, driven by self-consciousness, social consciousness, credibility, and social presence, significantly influences the impact of self-expressive products on the audience’s purchase intention. The research contributes to micro-influence marketing theory by integrating mechanics, offering practical implications for micro-influencers, and suggesting future research agendas.
Attentional Bias of Individuals with Social Anxiety towards Facial and Somatic Emotional Cues in a Holistic Manner
Authors: Wang Yuetan , Liang Jingjing , Zhu Ziwen , Gao Jingyi , Yao Qiuyan , Ding Xiaobin
Published: March 2024

Attentional bias towards threatening information is a crucial factor contributing to the development and persistence of social anxiety. However, the attentional bias towards threat information and the preferential processing pattern of emotional cues in individuals with social anxiety disorder during integrated facial and physical stimuli processing remain unclear. In this study, we employed a dot-probe paradigm to investigate the attentional bias towards integrated emotions (facial–body) among students with high and low levels of social anxiety (Experiment 1). Experiments 2 and 3 examined the attentional bias of socially anxious individuals when faced with conflicting emotional cues from faces or bodies in relation to integrated emotions. The data revealed that participants both high and low levels of social anxiety participants exhibited accelerated orienting and biased attention towards facial–body emotional processing. When there was inconsistency between emotional cues from faces or bodies and integrated emotions, higher levels of social anxiety were associated with increased vigilance towards threatening faces or bodies. These findings underscore that individuals with social anxiety possess an ability to rapidly capture threatening cues during the processing of facial–body emotional stimuli while also demonstrating a tendency to avoid relying solely on facial cues by compensating through bodily cues for emotion perception.
Multivariate Evaluation of Photovoltaic Utilization Potential of Primary and Secondary School Buildings: A Case Study in Hainan Province, China
Authors: Wang Chaohong , Zhang Xudong , Chen Wang , Jiang Feihu , Zhao Xiaogang
Published: March 2024

Modernization and industrialization have significantly increased energy consumption, causing environmental problems. Given that China is the largest energy user, the rise in building energy consumption necessitates clean energy alternatives. The purpose of this study is to summarize typical building models for primary and secondary schools in Hainan Province, and to use software to simulate and calculate the photovoltaic utilization potential of primary and secondary school buildings. In China, the government is usually the manager of primary and secondary schools, and due to their architectural characteristics, these buildings can be used to assess photovoltaic applications. The aim is to drive the application of photovoltaic systems in all types of buildings and promote urban energy reform. This study summarizes the types of primary and secondary school buildings in Hainan Province and analyzes them. It evaluates rooftop photovoltaic projects at the Second Middle School and the Siyuan School in Wanning City, Hainan Province, and uses PVsyst 7.2 software to assess the photovoltaic utilization potential. The results show that the optimal orientation in Hainan Province is south-facing, and the optimal inclination angle is 10° to 20°. The most favorable orientations of facade photovoltaic systems are 20° southeast or southwest. The longest dynamic investment payback period is approximately 15 years, and the environmental benefits are $0.012/kWh. The findings indicate significant potential for photovoltaic applications in primary and secondary school buildings. A combination of facade and rooftop photovoltaics can result in the zero-energy consumption of these buildings, reducing the pressure on urban power grids and achieving sustainable utilization.
Research on the Permeability and Pore Structure Distribution Characteristics of High-Performance Mortar for Surface Treatment of Bridge Piers and Columns
Authors: Yu Xianzheng , Liu Hua , Fan Xiaolin , Zhu Liangyu , Zhang Chengqi , Zhang Shiyi
Published: March 2024

In marine environments, bridge piers and columns are prone to corrosion caused by harmful media, particularly chloride ions. This corrosion can lead to cracking of the steel bars in the protective layer of the bridge piers. To enhance the corrosion resistance of concrete in bridge piers, this article introduces the use of nanoclay-modified cement mortar. This innovative material offers high-performance surface treatment options that can effectively slow down the erosion process of harmful media and reduce the risk of bridge pier column cracking. To evaluate the ion erosion resistance of this nanoclay-modified cement mortar, we conducted detailed experiments on the pore structure of cement paste. The pore structure of cement paste with different dosages of nano-kaolinite clay and the dispersion method was studied using mercury intrusion porosimetry (MIP). The fractal dimension of the pore surface area of the net cement paste was calculated from the fractal model based on thermodynamic relationships of the pore structure-related parameters obtained with mercury pressure experiments. The relationship among the multiple fractal dimensions, pore structure parameters, dispersion mode, and permeability is explored. The results show that the addition of nano-kaolinite clay particles can improve the internal pore structure of cement materials. When 1.5% nano-kaolinite clay is mechanical dispersed, the total specific pore volume and the most probable pore size are reduced by 47.83% and 56.87%, respectively, compared with the control group. The fractal dimension image of cement-based materials with nano-kaolinite clay has a range of singular points and does not have fractal characteristics in this range. Nano-kaolinite clay has a significant effect on the fractal dimension of pore size range I. The fractal dimension of the whole pore size range is not suitable for the analysis of permeability, and the fractal dimension calculated by selecting less than the critical pore size range has a good correlation with permeability.
Leadership in Energy and Environmental Design Commercial Interior Version 4 (LEED-CI v4) Gold-Certified Office Space Projects: A Pairwise Comparative Analysis between Three Mediterranean Countries
Authors: Pushkar Svetlana
Published: March 2024

Over the past five years, Leadership in Energy and Environmental Design Commercial Interior version 4 (LEED-CI v4)-certified office projects have been intensively studied in the USA and China, but they have not yet been studied in the Mediterranean region. The purpose of this study was to explore office building certification strategies for LEED-CI v4-certified projects in the Mediterranean region. The study design included pairwise comparative analyses between Spain (number of projects (n) n1 = 14), Türkiye (n2 = 13), and Israel (n3 = 11). Cliff’s δ and exact Wilcoxon–Mann–Whitney tests were used to process ordinal and discrete data, while the natural logarithm of the odds ratio and 2 × 2 Fisher’s exact tests were used to handle dichotomous data. It was found that Spain and Türkiye outperformed Israel in the Location and Transportation (LT) category due to their desire to reduce the use of private transport. Spain and Türkiye were ahead of Israel in the LTc5 “reduced parking footprint” credit (p = 0.008 and 0.0005, respectively). Israel outperformed Spain and Türkiye in the Energy and Atmosphere (EA) category due to the sum of all six EA credits (p = 0.086 and 0.010). Spain overtook Türkiye and Israel in the Materials and Resources (MRs) category due to Spain’s increased use of environmental product declarations. Spain and Türkiye were ahead of Israel in the following four MRs credits: MRc1 “long-term commitment” (p = 0.030), MRc2 “interiors life cycle impact reduction” (p = 0.037), MRc3 “building product disclosure and optimization—environmental product declarations” (p = 0.029), and MRc5 “building product disclosure and optimization—material ingredients” (p = 0.034). Spain, Türkiye, and Israel showed similarly low levels of achievement in the Indoor Environmental Quality (EQ) category (p ≥ 0.405). However, Spain and Türkiye outperformed Israel in the following two credits: EQc1 “enhanced indoor air quality strategies” and EQc2 “low-emitting materials” (p = 0.001 and 0.060, respectively). In parallel, Israel outperformed Türkiye in the EQc3 “construction indoor air quality management plan” (p = 0.026), and Israel outperformed Spain in the EQc8 “quality views” credit (p = 0.066). As a result, a pairwise comparison of the three Mediterranean countries showed that each country has a unique LEED certification strategy. Knowledge of the above green building strategies will be helpful for LEED professionals.
Nonlinear Analysis of Bearing Characteristics of Stiffened Deep Cement Mixing Piles under Vertical Loading
Authors: Jiu Yongzhi , Gao Yunfeng , Lei Fuguang , Zhu Yanzhi , Zhang Zhizeng
Published: March 2024

Stiffened deep cement mixing (SDCM) piles are composite piles that combine the advantages of single large-diameter deep cement mixing (DCM) and precast concrete piles. They comprise precast concrete piles as the core and cast-in-place DCM piles as the outer layer. This study evaluates the bearing characteristics of SDCM piles under vertical loading. The composite modulus of elasticity of SDCM piles is first introduced and determined using the area-weighted average method. Then, the reliability of the proposed method is described by comparing the calculated results with the findings of the existing literature. Furthermore, a nonlinear simplified analysis method based on the load transfer method is proposed for vertical bearing characteristics of equal- and short-core SDCM piles under vertical loading. This method is developed by the finite difference method. The accuracy of the simplified method is validated by comparing its results with those from existing tests, theoretical analysis, and finite element simulations. The results of their study indicated that the area-weighted average method calculates the composite modulus of elasticity of the composite pile section of the SDCM piles with an error below 0.5% compared to the analytical method. This finding represents sufficient accuracy. The simplified calculation method established in this study is computationally stable. When the iteration factor is set to 10−6, as the number of discrete nodes n on the pile increases, the calculation results are stable with a good convergence when n > 30. The vertical bearing capacity and pile top stiffness of SDCM piles increased with the length of the core piles. There was a reasonable core-to-length ratio for SDCM piles in specific scenarios. An excessively long DCM pile section made its lower part force-free for a given length of core piles. The appropriate length of core piles should be determined in actual projects to avoid unnecessary material waste. An optimum ratio of core piles for SDCM piles was determined. Beyond this optimal value, an increase in the ratio of core piles controlled the pile settlement in a limited manner.
Creativity in Project Implementation: An Empirical Study of Project Managers
Authors: Almashhour Raghad , Abuzaid Haneen , El-Sayegh Sameh
Published: March 2024

The construction industry is a dynamic and ever-evolving sector, continuously adapting to societal needs. Within this context, project managers play a pivotal role in steering projects from inception to completion. This study delves into the vital dimension of creativity among project managers in the United Arab Emirates (UAE) and its substantial contribution to the growth of the construction industry in the region. Research in the broader field of construction and project management has traditionally concentrated on factors such as scheduling, cost control, and risk management. However, a noticeable gap exists in the exploration of the relationship between project manager creativity and project success. Hence, the objective of this study is to comprehensively explore various dimensions of project managers’ creativity and evaluate its influence, alongside other criteria, on the outcomes of construction projects. Dimensions and indicators of creativity are derived from a meticulous literature review, and online survey questionnaires were employed to gather insights from individuals engaged in construction projects. The resulting hypothetical model underwent rigorous statistical analysis, employing confirmatory factor analysis and structural equation modeling. Findings indicate a positive impact of tacit knowledge sharing and emotional intelligence on the creativity of construction project managers in the UAE. Moreover, the study establishes that project managers’ creativity, combined with other criteria, significantly contributes to the success of construction projects in the region. These insights are instrumental for fostering creativity among project managers and enhancing overall project success within the construction industry. The study’s originality lies in its distinct contribution to the discourse on creativity in the construction sector.
Identifying Damage in Structures: Definition of Thresholds to Minimize False Alarms in SHM Systems
Authors: Ditommaso Rocco , Ponzo Felice Carlo
Published: March 2024

In recent years, the development of quick and streamlined methods for the detection and localization of structural damage has been achieved by analysing key dynamic parameters before and after significant events or as a result of aging. Many Structural Health Monitoring (SHM) systems rely on the relationship between occurred damage and variations in eigenfrequencies. While it is acknowledged that damage can affect eigenfrequencies, the reverse is not necessarily true, particularly for minor frequency variations. Thus, reducing false positives is essential for the effectiveness of SHM systems. The aim of this paper is to identify scenarios where observed changes in eigenfrequencies are not caused by structural damage, but rather by non-stationary combinations of input and system response (e.g., wind effects, traffic vibrations), or by stochastic variations in mass, damping, and stiffness (e.g., environmental variations). To achieve this, statistical variations of thresholds were established to separate linear non-stationary behaviour from nonlinear structural behaviour. The Duffing oscillator was employed in this study to perform various nonlinear analyses via Monte Carlo simulations.
Flexural Performances of Novel Wet Joints with Sleeve Connections in Precast Composite Floor System
Authors: Zhang Wenbin , Feng Yan , Zeng Xiangqiang , Xu Ming , Gong Liang , Rui Lijun
Published: March 2024

A new type of assembled integral multi-ribbed composite floor system with novel wet joint and steel sleeve connections, which exhibits satisfactory strength and stiffness, was proposed in the previous study. To further study the flexural performances of the joints, six groups of specimens, including two cast in situ concrete slabs and four composite slabs sized 4700 mm × 1200 mm × 300 mm and 2450 mm × 1200 mm × 300 mm, were investigated under four-point flexural tests. Four main influence factors were experimentally studied, i.e., casting methods, joint amounts, shear span lengths, and steel sleeve layout directions, on the failure modes, crack distributions, and deflection–load carrying capacity relationship. Test results indicated that the proposed composite slab system could provide the ultimate bearing capacity lower by 7% than that of the cast in situ concrete slabs, largely exceeding the code-predicted strength. No strain difference between the steel sleeve connections and steel rebars indicated good wet joint connection behavior. More hollow-core sections and long shear spans increased the potential of interfacial splitting cracks, leading to a shorter elastic stage and lower elastic stiffness. A finite element model was further parametrically conducted to explore the structural performances. Finite element results also indicate that the precast concrete slab had a more significant influence on the failure loads than the influences of concrete compressive strength and lap-splice steel rebar strength. These findings indicate that the proposed composite slab systems possess a satisfactory performance in the ultimate bearing capacity and deformability. Thus, such an assembled integral multi-ribbed composite floor system can be widely applied in construction.
De-Escalation Surgery in cT3-4 Breast Cancer Patients after Neoadjuvant Therapy: Predictors of Breast Conservation and Comparison of Long-Term Oncological Outcomes with Mastectomy
Authors: Tinterri Corrado , Barbieri Erika , Sagona Andrea , Bottini Alberto , Canavese Giuseppe , Gentile Damiano
Published: March 2024

Background: Neoadjuvant therapy (NAT) has become increasingly employed for the treatment of cT3-4 breast cancer (BC), enabling breast-conserving surgery (BCS) in cases traditionally considered for mastectomy. This study aims to identify predictors for breast conservation post-NAT and to evaluate whether BCS influences long-term oncological outcomes. Methods: We retrospectively analyzed data from patients with cT3-4 BC who received NAT at the Breast Unit of IRCCS Humanitas Research Hospital, Milan, Italy, from October 2009 to April 2020. Surgical outcomes and long-term oncological results, such as disease-free survival (DFS), distant DFS (DDFS), overall survival (OS), and BC-specific survival (BCSS), were compared between the BCS and mastectomy groups. Results: Among 114 patients analyzed, 37 (32.5%) underwent BCS, and 77 (67.5%) had a mastectomy. The key predictors for opting for BCS included absence of vascular invasion, reduced tumor size post-NAT, and achieving ypT0 status. No significant differences in DFS, DDFS, OS, and BCSS were observed between the two surgical groups (log-ranks, p = 0.520, p = 0.789, p = 0.216, p = 0.559, respectively). Conclusions: BCS after NAT is a feasible and safe option for patients with cT3-4 BC, without adversely affecting long-term oncological outcomes. Identifying predictors of breast conservation can guide surgical decision-making, ensuring that patients receive optimal treatment.
Immune Checkpoint Inhibitors and Male Fertility: Should Fertility Preservation Options Be Considered before Treatment?
Authors: Ntemou Elissavet , Delgouffe Emily , Goossens Ellen
Published: March 2024

In recent years, immune checkpoint inhibitors (ICIs) have become a viable option for many cancer patients, including specific subgroups of pediatric patients. Despite their efficiency in treating different types of cancer, ICIs are responsible for a number of immune-related adverse events, including inflammatory toxicities, that can affect several organs. However, our knowledge of the impact of ICIs on the testis and male fertility is limited. It is possible that ICI treatment affects testicular function and spermatogenesis either directly or indirectly (or both). Treatment with ICIs may cause increased inflammation and immune cell infiltration within the seminiferous tubules of the testis, disturbing spermatogenesis or testosterone deficiency (primary hypogonadism). Additionally, the interference of ICIs with the hypothalamic–pituitary–gonadal axis may alter testosterone production, affecting testicular function (secondary hypogonadism) and spermatogenesis. This review provides an overview of the available evidence on the potential association between ICIs and the disruption of spermatogenesis, with special focus on ICIs targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1). Moreover, it highlights the need for further investigations and encourages the discussion of associated risks and fertility-preservation considerations between clinicians and patients.
Lung NETs and GEPNETs: One Cancer with Different Origins or Two Distinct Cancers?
Authors: Evangelou Georgios , Vamvakaris Ioannis , Papafili Anastasia , Anagnostakis Maximilian , Peppa Melpomeni
Published: March 2024

Lung neuroendocrine tumors (LNETs) and gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are two distinct types of neuroendocrine tumors (NETs) that have traditionally been treated as a single entity despite originating from different sources. Although they share certain phenotypic characteristics and the expression of neuroendocrine markers, they exhibit differences in their microenvironment, molecular mutations, and responses to various therapeutic regimens. Recent research has explored the genetic alterations in these tumors, revealing dissimilarities in the frequently mutated genes, the role of EGFR in carcinogenesis, the presence of transcription factors, and the immunogenicity of the tumor and its microenvironment. Spread Through Air Spaces (STAS), a phenomenon unique to lung carcinomas, appears to play a crucial role in LNET prognosis. These distinctions are also evident in the cascade response of lung and GI tract neuroendocrine tumors to somatostatin analogs, Peptide Receptor Radionuclide Therapy (PRRT), chemotherapy, and immunotherapy. Identifying similarities and differences between the two groups may improve our understanding of the underlying mechanisms and facilitate the development of more effective treatment strategies.
PIP4K2B Protein Regulation by NSD1 in HPV-Negative Head and Neck Squamous Cell Carcinoma
Authors: Topchu Iuliia , Bychkov Igor , Roshchina Ekaterina , Makhov Petr , Boumber Yanis
Published: March 2024

Head and neck squamous cell carcinoma (HNSCC) ranks among the most prevalent global cancers. Despite advancements in treatments, the five-year survival rate remains at approximately 66%. The histone methyltransferase NSD1, known for its role in catalyzing histone H3 lysine 36 di-methylation (H3K36me2), emerges as a potential oncogenic factor in HNSCC. Our study, employing Reverse Phase Protein Array (RPPA) analysis and subsequent validation, reveals that PIP4K2B is a key downstream target of NSD1. Notably, PIP4K2B depletion in HNSCC induces downregulation of the mTOR pathway, resulting in diminished cell growth in vitro. Our investigation highlights a direct, positive regulatory role of NSD1 on PIP4K2B gene transcription through an H3K36me2-dependent mechanism. Importantly, the impact of PIP4K2B appears to be context-dependent, with overexpression rescuing cell growth in laryngeal HNSCC cells but not in tongue/hypopharynx cells. In conclusion, our findings implicate PIP4K2B as a novel NSD1-dependent protein in HNSCC, suggesting its potential significance for laryngeal cancer cell survival. This insight contributes to our understanding of the molecular landscape in HNSCC and establishes PIP4KB as a promising target for drug development.
Systemic Chemotherapy in Colorectal Peritoneal Metastases Treated with Cytoreductive Surgery: Systematic Review and Meta-Analysis
Authors: Tonello Marco , Cenzi Carola , Pizzolato Elisa , Fiscon Riccardo , Del Bianco Paola , Pilati Pierluigi , Sommariva Antonio
Published: March 2024

Background. For patients with colorectal cancer (CRC) peritoneal metastases (PM) who are eligible for cytoreductive surgery (CRS), the indication and timing of systemic chemotherapy (SC) are still under debate. This study aims to analyze the role of pre, post or perioperative SC on the survival and surgical complications of patients treated with CRS-HIPEC. Methods. After a systematic search in MEDLINE, Cochrane Database of Systematic Reviews, Scopus, Web of Science and Embase, a meta-analysis was performed to compare postoperative complications, disease-free survival (DFS) and overall survival (OS) according to SC administration and timing. PROSPERO: CRD42023478977. Results. Of 1203 studies screened, 15 were included in the meta-analysis (4523 patients). Post-operative SC was associated with increased overall survival (post-SC vs. no post-SC: HR 0.81, p = 0.00001, I2 = 0%; pre-SC vs. post-SC: HR 0.65, p = 0.01, I2 = 28%), whereas SC (pre or post) or pre-SC compared to surgery alone was not (SC vs. no SC: p = 0.29, I2 = 80%; pre-SC vs. no pre-SC: p = 0.59, I2 = 58%). Similar results were seen for DFS. SC was not associated with an increased complication rate (p = 0.47, I2 = 64%). Conclusions. Systemic chemotherapy administration in patients undergoing radical surgery for colorectal peritoneal metastases is associated with increased survival only in the adjuvant/post-operative setting. Considering the limitations of the included studies, further trials are needed to answer this unresolved question.
Molecular Pathology of Pancreatic Cystic Lesions with a Focus on Malignant Progression
Authors: Hu Yan , Jones Dan , Esnakula Ashwini K. , Krishna Somashekar G. , Chen Wei
Published: March 2024

The malignant progression of pancreatic cystic lesions (PCLs) remains understudied with a knowledge gap, yet its exploration is pivotal for effectively stratifying patient risk and detecting cancer at its earliest stages. Within this review, we delve into the latest discoveries on the molecular level, revealing insights into the IPMN molecular landscape and revised progression model, associated histologic subtypes, and the role of inflammation in the pathogenesis and malignant progression of IPMN. Low-grade PCLs, particularly IPMNs, can develop into high-grade lesions or invasive carcinoma, underscoring the need for long-term surveillance of these lesions if they are not resected. Although KRAS and GNAS remain the primary oncogenic drivers of neoplastic development in IPMNs, additional genes that are important in tumorigenesis have been recently identified by whole exome sequencing. A more complete understanding of the genes involved in the molecular progression of IPMN is critical for effective monitoring to minimize the risk of malignant progression. Complicating these strategies, IPMNs are also frequently multifocal and multiclonal, as demonstrated by comparative molecular analysis. Algorithms for preoperative cyst sampling and improved radiomic techniques are emerging to model this spatial and temporal genetic heterogeneity better. Here, we review the molecular pathology of PCLs, focusing on changes associated with malignant progression. Developing models of molecular risk stratification in PCLs which can complement radiologic and clinical features, facilitate the early detection of pancreatic cancer, and enable the development of more personalized surveillance and management strategies are summarized.
TP53 and/or BRCA1 Mutations Based on CtDNA Analysis as Prognostic Biomarkers for Primary Triple-Negative Breast Cancer
Authors: Arimura Akiko , Sakai Kazuko , Kaneshiro Kazuhisa , Morisaki Takafumi , Hayashi Saori , Mizoguchi Kimihisa , Yamada Mai , Kai Masaya , Ono Mayumi , Nishio Kazuto , Nakamura Masafumi , Kubo Makoto
Published: March 2024

Precise biomarkers for predicting the therapeutic efficacy of molecularly targeted drugs are limited at the protein level; thus, it has been important to broadly scrutinize individual cancer driver gene mutations for effective cancer treatments. Multiplex cancer genome profiling can comprehensively identify gene mutations that are therapeutic targets using next-generation sequencing (NGS). In addition, circulating tumor DNA (ctDNA) is a DNA fragment released into the blood by tumor cell-derived cell death or apoptosis. Liquid biopsy with ctDNA is a novel clinical test for identifying genetic mutations in an entire population noninvasively, in real-time, and heterogeneously. Although there are several reports on ctDNA, fewer have evaluated ctDNA with NGS before an initial treatment for breast cancer patients. Therefore, we examined whether analyzing tumor-associated gene mutations in primary breast cancer based on ctDNA could serve as a biomarker for prognosis and optimal treatment selection. Ninety-five primary breast cancer patients treated at our department from January 2017 to October 2020 were included. Pretreatment plasma samples were subjected to NGS analysis of ctDNA, and correlations with patients’ clinicopathological characteristics were evaluated. Fifty-nine (62.1%) patients were positive for ctDNA. ctDNA tended to be positive in hormone receptor-negative, and TP53 (34%), BRCA1 (20%), and BRCA2 (17%) gene mutations were more frequent. Regarding recurrence-free survival, the prognosis was poor in the TP53 and/or BRCA1 mutation-positive groups, especially in triple-negative breast cancer (TNBC) patients. In conclusion, the results of this study indicate that ctDNA with liquid biopsy could identify the poor prognosis group before treatment among TNBC patients and for those for whom optimal treatment selection is desirable; additionally, optimal treatment could be selected according to the ctDNA analysis results.
EMT Dynamics in Lymph Node Metastasis of Oral Squamous Cell Carcinoma
Authors: Ghantous Yasmine , Mozalbat Shiraz , Nashef Aysar , Abdol-Elraziq Murad , Sudri Shiran , Araidy Shareef , Tadmor Hagar , Abu El-naaj Imad
Published: March 2024

Background: Epithelial–mesenchymal transition (EMT) enables tumor cell invasion and metastasis. Many studies have demonstrated the critical role of EMT in lymph node metastasis in oral squamous cell carcinoma (OSCC). During EMT, epithelial cancer cells lose intercellular adhesion and apical–basal polarity and acquire mesenchymal properties such as motility and invasiveness. A significant feature of EMT is cadherin switching, involving the downregulation of E-cadherin and upregulation of N-cadherin. The TGF-β/SMAD pathway can also induce EMT. We aimed to evaluate EMT markers as predictors of lymph node metastasis in OSCC. Methods: We performed genetic profiling of 159 primary OSCCs from TCGA and analyzed the expression of EMT markers, including cadherin switch genes (CDH1, CDH2), and TGF-β/SMAD pathway genes. Samples were divided into advanced (stage III–IV) and early (stage I–II) stage groups. Differential expression analysis was performed, as well as an independent validation study containing fresh OSCC samples. Results: TGF-β/SMAD pathway genes such as SMAD6 were upregulated in advanced stage tumors. N-cadherin and SNAIL2 were overexpressed in node-positive tumors. Keratins were downregulated in these groups. Conclusion: Our findings demonstrate that EMT marker expression correlates with lymph node metastasis in OSCC. Developing therapies targeting regulators such as N-cadherin may prevent metastasis and improve outcomes.
Exercise Suppresses Head and Neck Squamous Cell Carcinoma Growth via Oncostatin M
Authors: Yoshimura Takuya , Hirano Yuka , Hamada Taiji , Yokoyama Seiya , Suzuki Hajime , Takayama Hirotaka , Migita Hirono , Ishida Takayuki , Nakamura Yasunori , Ohsawa Masahiro , Asakawa Akihiro , Ishihata Kiyohide , Tanimoto Akihide
Published: March 2024

Major advances have been made in cancer treatment, but the prognosis for elderly cancer patients with sarcopenia and frailty remains poor. Myokines, which are thought to exert preventive effects against sarcopenia, have been reported to be associated with the prognosis of various cancers, but their effect on head and neck squamous cell carcinoma (HNSCC) is unknown. The aim of this study was to clarify the influence of exercise on the control of HNSCC and to examine the underlying mechanism involved. Mice were injected with HSC-3-M3 cells, a human cell line of highly metastatic and poorly differentiated tongue cancer, at the beginning of the study. Just prior to transplantation, blood was collected from the mice, and the levels of myokines were measured by ELISA. Oncostatin M (OSM), a selected myokine, was added to HSC-3-M3 cells, after which the cell proliferation ability, cell cycle, and protein expression were analyzed in vitro. Tumor cell viability was lower (control: 100%, exercise: 75%), tumors were smaller (control: 26.2 mm3, exercise: 6.4 mm3), and survival was longer in the exercise group than in the control group in vivo. OSM inhibited HSC-3-M3 cell proliferation in a concentration-dependent manner in vitro. The addition of OSM increased the proportion of cells in the G0/G1 phase, decreased the proportion of cells in the G2/M phase, and increased the expression of the CDK inhibitors p21 and p27. These results indicate that exercise may directly inhibit the proliferation of HNSCC cell lines via OSM.
Responses to Medical Treatment in 192 Patients with Pancreatic Neuroendocrine Neoplasms Referred to the Copenhagen Neuroendocrine Tumour Centre in 2000–2020
Authors: Petersen Sofie Skovlund , Møller Stine , Slott Cecilie , Krogh Jesper , Hansen Carsten Palnæs , Kjaer Andreas , Holmager Pernille , Oturai Peter , Garbyal Rajendra Singh , Langer Seppo W. , Knigge Ulrich , Andreassen Mikkel
Published: March 2024

Background: Given the rarity and heterogeneity of pancreatic neuroendocrine neoplasms (pNEN), treatment algorithms and sequencing are primarily guided by expert opinions with limited evidence. Aim: To investigate overall survival (OS), median progression-free survival (mPFS), and prognostic factors associated with the most common medical treatments for pNEN. Methods: Retrospective single-center study encompassing patients diagnosed and monitored between 2000 and 2020 (n = 192). Results: Median OS was 36 (95% CI: 26–46) months (99 months for grade (G) 1, 62 for G2, 14 for G3, and 10 for neuroendocrine carcinomas). Patients treated with somatostatin analogues (SSA) (n = 59, median Ki-67 9%) had an mPFS of 28 months. Treatment line (HR (first line as reference) 4.1, 95% CI: 1.9–9.1, p ≤ 0.001) emerged as an independent risk factor for time to progression. Patients with a Ki-67 index ≥10% (n = 28) had an mPFS of 27 months. Patients treated with streptozocin/5-fluorouracil (STZ/5FU) (n = 70, first-line treatment n = 68, median Ki-67 10%) had an mPFS of 20 months, with WHO grade serving as an independent risk factor (HR (G1 (n = 8) vs. G2 (n = 57)) 2.8, 95% CI: 1.1–7.2, p-value = 0.031). Median PFS was 21 months for peptide receptor radionuclide therapy (PRRT) (n = 41, first line n = 2, second line n = 29, median Ki-67 8%), 5 months for carboplatin and etoposide (n = 66, first-line treatment n = 60, median Ki-67 80%), and 3 months for temozolomide-based therapy (n = 56, first-line treatment n = 17, median Ki-67 30%). Conclusion: (1) Overall survival was, as expected, highly dependent on grade; (2) median PFS for SSA was around 2.5 years without difference between tumors with Ki-67 above or below 10%; (3) STZ/5FU as first-line treatment exhibited a superior mPFS of 20 months compared to what has historically been reported for targeted treatments; (4) PRRT in G2 pNEN achieved an mPFS similar to first-line chemotherapy; and (5) limited treatment efficacy was observed in high-grade tumors when treated with carboplatin and etoposide or temozolomide.
Cancer Screening: Present Recommendations, the Development of Multi-Cancer Early Development Tests, and the Prospect of Universal Cancer Screening
Authors: Galeș Laurenția Nicoleta , Păun Mihai-Andrei , Anghel Rodica Maricela , Trifănescu Oana Gabriela
Published: March 2024

Cancer continues to pose a considerable challenge to global health. In the search for innovative strategies to combat this complex enemy, the concept of universal cancer screening has emerged as a promising avenue for early detection and prevention. In contrast to targeted approaches that focus on specific populations or high-risk individuals, universal screening seeks to cast a wide net to detect incipient malignancies in different demographic groups. This paradigm shift in cancer care underscores the importance of comprehensive screening programs that go beyond conventional boundaries. As our understanding of the complex molecular and genetic basis of cancer deepens, the need to develop comprehensive screening methods becomes increasingly apparent. In this article, we look at the rationale and potential benefits of universal cancer screening.
The Added Value of Transcatheter CT Hepatic Angiography (CTHA) Image Guidance in Percutaneous Thermal Liver Ablation: An Experts’ Opinion Pictorial Essay
Authors: Puijk Robbert S. , Dijkstra Madelon , van der Lei Susan , Schulz Hannah H. , Vos Danielle J. W. , Timmer Florentine E. F. , Geboers Bart , Scheffer Hester J. , de Vries Jan J. J. , Smits Maarten L. J. , Bruijnen Rutger C. G. , Deschamps Frédéric , de Baère Thierry , Odisio Bruno C. , Meijerink Martijn R.
Published: March 2024

With the rapidly evolving field of image-guided tumor ablation, there is an increasing demand and need for tools to optimize treatment success. Known factors affecting the success of (non-)thermal liver ablation procedures are the ability to optimize tumor and surrounding critical structure visualization, ablation applicator targeting, and ablation zone confirmation. A recent study showed superior local tumor progression-free survival and local control outcomes when using transcatheter computed tomography hepatic angiography (CTHA) guidance in percutaneous liver ablation procedures. This pictorial review provides eight clinical cases from three institutions, MD Anderson (Houston, TX, USA), Gustave Roussy (Paris, France), and Amsterdam UMC (Amsterdam, The Netherlands), with the intent to demonstrate the added value of real-time CTHA guided tumor ablation for primary liver tumors and liver-only metastatic disease. The clinical illustrations highlight the ability to improve the detectability of the initial target liver tumor(s) and identify surrounding critical vascular structures, detect ‘vanished’ and/or additional tumors intraprocedurally, differentiate local tumor progression from non-enhancing scar tissue, and promptly detect and respond to iatrogenic hemorrhagic events. Although at the cost of adding a minor but safe intervention, CTHA-guided liver tumor ablation minimizes complications of the actual ablation procedure, reduces the number of repeat ablations, and improves the oncological outcome of patients with liver malignancies. Therefore, we recommend adopting CTHA as a potential quality-improving guiding method within the (inter)national standards of practice.
Catalytic Activity Prediction of α-Diimino Nickel Precatalysts toward Ethylene Polymerization by Machine Learning
Authors: Abbas Zaheer , Meraz Md Mostakim , Yang Wenhong , Yang Weisheng , Sun Wen-Hua
Published: March 2024

The present study explored machine learning methods to predict the catalytic activities of a dataset of 165 α-diimino nickel complexes in ethylene polymerization. Using 25 descriptors as the inputs, the XGBoost model presented the optimal performance among six different algorithms (R2 = 0.999, Rt2 = 0.921, Q2 = 0.561). The results of the analysis indicate that high activity is related to the presence of polarizable atoms and less bulky substituents within the N-aryl group. This approach offers valuable insights on the variation principle of catalytic activity as a function of complex structure, helping to effectively design and optimize α-diimino Ni catalysts with desirable performance.
Transformation of Light Alkanes into High-Value Aromatics
Authors: Akhtar Muhammad Naseem
Published: March 2024

This research work is focused on the transformation of light alkane (propane) into high-value aromatics using gallo-alumino-silicate catalysts. Two sets of gallo-alumino-silicates were synthesized for this study. In the first set, the ratio of Ga/(Al+Ga) was modified, while the Si/(Al+Ga) ratio was held constant. In the subsequent set, the Si/(Al+Ga) ratio was adjusted, while maintaining a consistent Ga/(Al+Ga) ratio. This approach aimed to directly assess the impact of each ratio on catalyst performance. The comprehensive characterization of all catalysts was conducted using various instrumental techniques, i.e., BET surface area, XRD, NH3-TPD, 27Al, 71Ga and 29Si MAS NMR, and XPS. A gradual reduction in the percentage of crystallinity and rise in meso-surface area was noticed with a rise in Ga/(Al+Ga) ratio. The total acidity (NH3-TPD) demonstrated a decline as the Si/(Al+Ga) ratio increased, attributed to an overall decline in Al3+ or Ga3+ species. The XPS intensity of the Ga 2p3/2 peak rose in correlation with an elevated ratio of Ga/(Al+Ga), suggesting the formation of extra-framework Ga species. The propane conversion, aromatic yield, and aromatization/cracking ratio exhibited an increase with an increasing Ga/(Al+Ga) ratio, reaching an optimum value of 0.46 before declining. Conversely, an appreciable drop in the conversion of propane and yield of aromatics was detected with the rise in Si/(Al+Ga) ratio, attributing to the decline in acidity. The catalyst having a Ga/(Al+Ga) ration of 0.46 exhibited the highest propane conversion and aromatic yield of 83.0% and 55.0% respectively.
Characterization of Lysophospholipase D Activity in Mammalian Cell Membranes
Authors: Xie Yuhuan , Ella Krishna M. , Gibbs Terra C. , Yohannan Marianne E. , Knoepp Stewart M. , Balijepalli Pravita , Meier G. Patrick , Meier Kathryn E.
Published: March 2024

Lysophosphatidic acid (LPA) is a lipid mediator that binds to G-protein-coupled receptors, eliciting a wide variety of responses in mammalian cells. Lyso-phospholipids generated via phospholipase A2 (PLA2) can be converted to LPA by a lysophospholipase D (lyso-PLD). Secreted lyso-PLDs have been studied in more detail than membrane-localized lyso-PLDs. This study utilized in vitro enzyme assays with fluorescent substrates to examine LPA generation in membranes from multiple mammalian cell lines (PC12, rat pheochromocytoma; A7r5, rat vascular smooth muscle; Rat-1, rat fibroblast; PC-3, human prostate carcinoma; and SKOV-3 and OVCAR-3, human ovarian carcinoma). The results show that membranes contain a lyso-PLD activity that generates LPA from a fluorescent alkyl-lyso-phosphatidylcholine, as well as from naturally occurring acyl-linked lysophospholipids. Membrane lyso-PLD and PLD activities were distinguished by multiple criteria, including lack of effect of PLD2 over-expression on lyso-PLD activity and differential sensitivities to vanadate (PLD inhibitor) and iodate (lyso-PLD inhibitor). Based on several lines of evidence, including siRNA knockdown, membrane lyso-PLD is distinct from autotaxin, a secreted lyso-PLD. PC-3 cells express GDE4 and GDE7, recently described lyso-PLDs that localize to membranes. These findings demonstrate that membrane-associated lyso-D activity, expressed by multiple mammalian cell lines, can contribute to LPA production.
Steroidogenesis Upregulation through Mitochondria-Associated Endoplasmic Reticulum Membranes and Mitochondrial Dynamics in Rat Testes: The Role of D-Aspartate
Authors: Latino Debora , Venditti Massimo , Falvo Sara , Grillo Giulia , Santillo Alessandra , Messaoudi Imed , Ben Rhouma Mariem , Minucci Sergio , Chieffi Baccari Gabriella , Di Fiore Maria Maddalena
Published: March 2024

Mitochondria-Associated Endoplasmic Reticulum Membranes (MAMs) mediate the communication between the Endoplasmic Reticulum (ER) and the mitochondria, playing a fundamental role in steroidogenesis. This study aimed to understand how D-aspartate (D-Asp), a well-known stimulator of testosterone biosynthesis and spermatogenesis, affects the mechanism of steroidogenesis in rat testes. Our results suggested that D-Asp exerts this function through MAMs, affecting lipid trafficking, calcium signaling, ER stress, and mitochondrial dynamics. After 15 days of oral administration of D-Asp to rats, there was an increase in both antioxidant enzymes (SOD and Catalase) and in the protein expression levels of ATAD3A, FACL4, and SOAT1, which are markers of lipid transfer, as well as VDAC and GRP75, which are markers of calcium signaling. Additionally, there was a decrease in protein expression levels of GRP78, a marker of aging that counteracts ER stress. The effects of D-Asp on mitochondrial dynamics strongly suggested its active role as well. It induced the expression levels of proteins involved in fusion (MFN1, MFN2, and OPA1) and in biogenesis (NRF1 and TFAM), as well as in mitochondrial mass (TOMM20), and decreased the expression level of DRP1, a crucial mitochondrial fission marker. These findings suggested D-Asp involvement in the functional improvement of mitochondria during steroidogenesis. Immunofluorescent signals of ATAD3A, MFN1/2, TFAM, and TOMM20 confirmed their localization in Leydig cells showing an intensity upgrade in D-Asp-treated rat testes. Taken together, our results demonstrate the involvement of D-Asp in the steroidogenesis of rat testes, acting at multiple stages of both MAMs and mitochondrial dynamics, opening new opportunities for future investigation in other steroidogenic tissues.
Immune Cells, Gut Microbiota, and Vaccines: A Gender Perspective
Authors: Rio Pierluigi , Caldarelli Mario , Chiantore Monica , Ocarino Francesca , Candelli Marcello , Gasbarrini Antonio , Gambassi Giovanni , Cianci Rossella
Published: March 2024

The development of preventive and therapeutic vaccines has played a crucial role in preventing infections and treating chronic and non-communicable diseases, respectively. For a long time, the influence of sex differences on modifying health and disease has not been addressed in clinical and preclinical studies. The interaction of genetic, epigenetic, and hormonal factors plays a role in the sex-related differences in the epidemiology of diseases, clinical manifestations, and the response to treatment. Moreover, sex is one of the leading factors influencing the gut microbiota composition, which could further explain the different predisposition to diseases in men and women. In the same way, differences between sexes occur also in the immune response to vaccines. This narrative review aims to highlight these differences, focusing on the immune response to vaccines. Comparative data about immune responses, vaccine effectiveness, and side effects are reviewed. Hence, the intricate interplay between sex, immunity, and the gut microbiota will be discussed for its potential role in the response to vaccination. Embracing a sex-oriented perspective in research may improve the efficacy of the immune response and allow the design of tailored vaccine schedules.