bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Ablative Techniques in the Management of Hepatocellular Carcinoma: Indications and Outcomes
Authors: Koza Asanda , Bhogal Ricky H. , Fotiadis Nicos , Mavroeidis Vasileios K.
Published: March 2023

The management of hepatocellular carcinoma (HCC) remains complex and will continue to rely on the multidisciplinary input of hepatologists, surgeons, radiologists, oncologists and radiotherapists. With the appropriate staging of patients and selection of suitable treatments, the outcomes for HCC are improving. Surgical treatments encompassing both liver resection and orthotopic liver transplantation (OLT) are the definitive curative-intent options. However, patient suitability, as well as organ availability, pose essential limitations. Consequently, non-surgical options, such as ablative techniques, play an increasingly important role, especially in small HCCs, where overall and disease-free survival can be comparable to surgical resection. Ablative techniques are globally recommended in recognised classification systems, showing increasingly promising results. Recent technical refinements, as well as the emerging use of robotic assistance, may expand the treatment paradigm to achieve improved oncological results. At present, in very early stage and early stage unresectable disease, percutaneous thermal ablation is considered the treatment of choice. Owing to their different features, various ablative techniques, including radiofrequency ablation, microwave ablation, cryotherapy ablation and irreversible electroporation, have been shown to confer different comparative advantages and applicability. We herein review the role of available ablative techniques in the current complex multidisciplinary management of HCC, with a main focus on the indications and outcomes, and discuss future perspectives.
Antifungal Drug Resistance: An Emergent Health Threat
Authors: Vitiello Antonio , Ferrara Francesco , Boccellino Mariarosaria , Ponzo Annarita , Cimmino Carla , Comberiati Emilio , Zovi Andrea , Clemente Salvatore , Sabbatucci Michela
Published: March 2023

Fungal infections, named mycosis, can cause severe invasive and systemic diseases that can even lead to death. In recent years, epidemiological data have recorded an increase in cases of severe fungal infections, caused mainly by a growing number of immunocompromised patients and the emergence of fungal pathogenic forms that are increasingly resistant to antimycotic drug treatments. Consequently, an increase in the incidence of mortality due to fungal infections has also been observed. Among the most drug-resistant fungal forms are those belonging to the Candida and Aspergillus spp. Some pathogens are widespread globally, while others are endemic in some areas only. In addition, some others may represent a health threat for some specific subpopulations and not for the general public. In contrast to the extensive therapeutic armamentarium available for the antimicrobial chemotherapeutic treatment of bacteria, for fungal infections there are only a few classes of antimycotic drugs on the market, such as polyenes, azoles, echinocandins, and a few molecules are under trial. In this review, we focused on the systemic mycosis, highlighted the antifungal drug compounds available in the pipeline, and analyzed the main molecular mechanisms for the development of antifungal resistance to give a comprehensive overview and increase awareness on this growing health threat.
Viscoelastic Properties of Zona Pellucida of Oocytes Characterized by Transient Electrical Impedance Spectroscopy
Authors: Azarkh Danyil , Cao Yuan , Floehr Julia , Schnakenberg Uwe
Published: March 2023

The success rate in vitro fertilization is significantly linked to the quality of the oocytes. The oocyte’s membrane is encapsulated by a shell of gelatinous extracellular matrix, called zona pellucida, which undergoes dynamic changes throughout the reproduction cycle. During the window of highest fertility, the zona pellucida exhibits a softening phase, while it remains rigid during oocyte maturation and again after fertilization. These variations in mechanical properties facilitate or inhibit sperm penetration. Since successful fertilization considerably depends on the state of the zona pellucida, monitoring of the hardening process of the zona pellucida is vital. In this study, we scrutinized two distinct genetic mouse models, namely, fetuin-B wild-type and fetuin-B/ovastacin double deficient with normal and super-soft zona pellucida, respectively. We evaluated the hardening with the help of a microfluidic aspiration-assisted electrical impedance spectroscopy system. An oocyte was trapped by a microhole connected to a microfluidic channel by applying suction pressure. Transient electrical impedance spectra were taken by microelectrodes surrounding the microhole. The time-depending recovery of zona pellucida deflections to equilibrium was used to calculate the Young’s modulus and, for the first time, absolute viscosity values. The values were obtained by fitting the curves with an equivalent mechanical circuit consisting of a network of dashpots and springs. The observer-independent electrical readout in combination with a fitting algorithm for the calculation of the viscoelastic properties demonstrates a step toward a more user-friendly and easy-to-use tool for the characterizing and better understanding of the rheological properties of oocytes.
Craft-and-Stick Xurographic Manufacturing of Integrated Microfluidic Electrochemical Sensing Platform
Authors: Kongkaew Supatinee , Meng Lingyin , Limbut Warakorn , Liu Guozhen , Kanatharana Proespichaya , Thavarungkul Panote , Mak Wing Cheung
Published: March 2023

An innovative modular approach for facile design and construction of flexible microfluidic biosensor platforms based on a dry manufacturing “craft-and-stick” approach is developed. The design and fabrication of the flexible graphene paper electrode (GPE) unit and polyethylene tetraphthalate sheet (PET)6/adhesive fluidic unit are completed by an economic and generic xurographic craft approach. The GPE widths and the microfluidic channels can be constructed down to 300 μm and 200 μm, respectively. Both units were assembled by simple double-sided adhesive tapes into a microfluidic integrated GPE (MF-iGPE) that are flexible, thin (<0.5 mm), and lightweight (0.4 g). We further functionalized the iGPE with Prussian blue and glucose oxidase for the fabrication of MF-iGPE glucose biosensors. With a closed-channel PET fluidic pattern, the MF-iGPE glucose biosensors were packaged and sealed to protect the integrated device from moisture for storage and could easily open with scissors for sample loading. Our glucose biosensors showed 2 linear dynamic regions of 0.05–1.0 and 1.0–5.5 mmol L−1 glucose. The MF-iGPE showed good reproducibility for glucose detection (RSD < 6.1%, n = 6) and required only 10 μL of the analyte. This modular craft-and-stick manufacturing approach could potentially further develop along the concept of paper-crafted model assembly kits suitable for low-resource laboratories or classroom settings.
eSEE-d: Emotional State Estimation Based on Eye-Tracking Dataset
Authors: Skaramagkas Vasileios , Ktistakis Emmanouil , Manousos Dimitris , Kazantzaki Eleni , Tachos Nikolaos S. , Tripoliti Evanthia , Fotiadis Dimitrios I. , Tsiknakis Manolis
Published: March 2023

Affective state estimation is a research field that has gained increased attention from the research community in the last decade. Two of the main catalysts for this are the advancement in the data analysis using artificial intelligence and the availability of high-quality video. Unfortunately, benchmarks and public datasets are limited, thus making the development of new methodologies and the implementation of comparative studies essential. The current work presents the eSEE-d database, which is a resource to be used for emotional State Estimation based on Eye-tracking data. Eye movements of 48 participants were recorded as they watched 10 emotion-evoking videos, each of them followed by a neutral video. Participants rated four emotions (tenderness, anger, disgust, sadness) on a scale from 0 to 10, which was later translated in terms of emotional arousal and valence levels. Furthermore, each participant filled three self-assessment questionnaires. An extensive analysis of the participants’ answers to the questionnaires’ self-assessment scores as well as their ratings during the experiments is presented. Moreover, eye and gaze features were extracted from the low-level eye-recorded metrics, and their correlations with the participants’ ratings are investigated. Finally, we take on the challenge to classify arousal and valence levels based solely on eye and gaze features, leading to promising results. In particular, the Deep Multilayer Perceptron (DMLP) network we developed achieved an accuracy of 92% in distinguishing positive valence from non-positive and 81% in distinguishing low arousal from medium arousal. The dataset is made publicly available.
Embodying Consciousness through Interoception and a Balanced Time Perspective
Authors: Klamut Olga , Weissenberger Simon
Published: March 2023

This review presents current research and scientific knowledge in body mind sciences through the lens of interoception, as a representative of the body; and time perspective, as the representative of the mind. This intertwining dichotomy has been a subject of discourse in many fields, all having the common denominator of consciousness. Our aim is to expand on the congruities of these seemingly deconstructed worlds-of science and philosophy, of the body and the mind, to show that the place of consciousness lies in the zone between these two. Being aware of the body in the present moment. We introduce interoception and time perspective, focusing on how interoceptive signals are depicted in autonomic nervous system (ANS) regulation, and how this relates to the concept of a balanced time perspective (BTP), a highly adaptive psychological characteristic. Time perspective and interoception are also reviewed in the case of clinical conditions. We assess findings on interoceptive pathways in the body, finding convergence with balanced time perspective through the neuroanatomical lens. We conclude with findings that both dysregulated interoceptive states and a time perspective disbalance are recognized as defining features of mental disorders, proposing prospective practical therapeutic approaches, as well as implications for further research in the field.
Classification of Migraine Using Static Functional Connectivity Strength and Dynamic Functional Connectome Patterns: A Resting-State fMRI Study
Authors: Nie Weifang , Zeng Weiming , Yang Jiajun , Zhao Le , Shi Yuhu
Published: March 2023

Migraine is a common, chronic dysfunctional disease with recurrent headaches. Its etiology and pathogenesis have not been fully understood and there is a lack of objective diagnostic criteria and biomarkers. Meanwhile, resting-state functional magnetic resonance imaging (RS-fMRI) is increasingly being used in migraine research to classify and diagnose brain disorders. However, the RS-fMRI data is characterized by a large amount of data information and the difficulty of extracting high-dimensional features, which brings great challenges to relevant studies. In this paper, we proposed an automatic recognition framework based on static functional connectivity (sFC) strength features and dynamic functional connectome pattern (DFCP) features of migraine sufferers and normal control subjects, in which we firstly extracted sFC strength and DFCP features and then selected the optimal features using the recursive feature elimination based on the support vector machine (SVM−RFE) algorithm and, finally, trained and tested a classifier with the support vector machine (SVM) algorithm. In addition, we compared the classification performance of only using sFC strength features and DFCP features, respectively. The results showed that the DFCP features significantly outperformed sFC strength features in performance, which indicated that DFCP features had a significant advantage over sFC strength features in classification. In addition, the combination of sFC strength and DFCP features had the optimal performance, which demonstrated that the combination of both features could make full use of their advantage. The experimental results suggested the method had good performance in differentiating migraineurs and our proposed classification framework might be applicable for other mental disorders.
A Bibliometric Analysis of Consumer Neuroscience towards Sustainable Consumption
Authors: Liu Yan , Zhao Rui , Xiong Xin , Ren Xinyun
Published: March 2023

Consumer neuroscience is a new paradigm for studying consumer behavior, focusing on neuroscientific tools to explore the underlying neural processes and behavioral implications of consumption. Based on the bibliometric analysis tools, this paper provides a review of progress in research on consumer neuroscience during 2000–2021. In this paper, we identify research hotspots and frontiers in the field through a statistical analysis of bibliometric indicators, including the number of publications, countries, institutions, and keywords. Aiming at facilitating carbon neutrality via sustainable consumption, this paper discusses the prospects of applying neuroscience to sustainable consumption. The results show 364 publications in the field during 2000–2021, showing a rapid upward trend, indicating that consumer neuroscience research is gaining ground. The majority of these consumer neuroscience studies chose to use electroencephalogram tools, accounting for 63.8% of the total publications; the cutting-edge research mainly involved event-related potential (ERP) studies of various marketing stimuli interventions, functional magnetic resonance imaging (fMRI)-based studies of consumer decision-making and emotion-specific brain regions, and machine-learning-based studies of consumer decision-making optimization models.
An Oriented H-BIM Approach for the Seismic Assessment of Cultural Heritage Buildings: Palazzo Vecchio in Florence
Authors: Cardinali Vieri , Ciuffreda Anna Livia , Coli Massimo , De Stefano Mario , Meli Francesca , Tanganelli Marco , Trovatelli Francesco
Published: March 2023

H-BIM paradigms are constituted by 3-D informative contents documenting the current and past state of existing structures. Although the transversal vision and the multidisciplinary interpretation have been attributed to BIM models, in the field of monumental structures, these databases can be organized in different ways depending on the adopted protocol and classifications for the required output of the work. In this manuscript, an H-BIM approach targeted at collecting and providing useful information to execute seismic vulnerability analyses of monumental structures is presented. The BIM modeling followed a protocol based on the following steps: geometrical acquisitions, scan-to-BIM modeling, and informative data collection. The methodology has been applied to the oldest part of Palazzo Vecchio in Florence (IT), an important monumental masonry structure representing the political headquarter of the city since the Middle Ages. The parametric modeling was realized classifying the information according to structural perspectives based on the cognitive steps for the investigation of the existing structures. Finally, a seismic assessment has been realized through a simplified procedure developed for cultural heritage buildings. The outcomes of the evaluation are still part of the collected information of the H-BIM model, as an example of continuous improvement of the available contents of the database.
Soil–Structure Interaction Consideration for Base Isolated Structures under Earthquake Excitation
Authors: Yanik Arcan , Ulus Yalcincan
Published: March 2023

This study aims to analytically implement base isolation with soil–structure interaction (SSI) on a sample structure and to develop a very simple solution to add these combined effects into the mass, damping and stiffness matrices of the structure. A spectrum analysis is also carried out considering the base-isolated structures and SSI. Dynamic simulations are performed throughout the study. In these simulations, three shear frame structures with different properties are considered. The strong ground motions selected for these analyses are eighteen different events with far-fault and near-fault components. In addition, four different base and soil structure combination cases are taken into account. These four analytical cases are a conventional structure with a fixed base and with SSI and a seismically isolated structure with or without the SSI. The numerical results showed that when SSI is considered, the effectiveness of the base isolation system may decrease, and the effect is prominent in softer soil conditions.
Seismic Performance of Concrete Column Connection with Square-Upper-Circular-Lower Steel Tube for Antique Buildings
Authors: Sun Xianghong , Guo Qingwei , Xuan Yunpeng , Wu Bingxue , Gao Jiabin
Published: March 2023

The antique building combines traditional design with contemporary technology, making it an important structural style. Columns, as a crucial structural component, directly affect how well the building functions as a whole. This paper proposes a new connection form with the upper square concrete-filled steel tube-lower circular concrete-filled steel tube (USCFST-LCCFST). This study investigates the seismic performance of the proposed connection form of the columns. First, the finite element software ABAQUS-2021 is used to simulate and analyze the connection forms of the upper square concrete-filled steel tube and lower circular reinforced concrete (USCFST-LCRC) and the upper square steel reinforced concrete and lower circular reinforced concrete (USSRC-LCRC) above the antique building, respectively, which confirms the rationality of the modeling method explored in this paper. Then, geometric modeling of the USCFST-LCCFST connection is performed using ABAQUS. Simulation results demonstrate the superior seismic performance of the proposed connection form. In addition, the influence law of steel tube yield strength and the ratio of upper and lower column linear stiffness on its seismic performance are analyzed and determined through the variational parameter analysis of the USCFST-LCCFST connection form. The steel tube yield strength of USCFST-LCCFST column connection components is recommended to be 355–420 MPa and the ratio of upper and lower column linear stiffness should be no less than 0.063. In order to ensure the good seismic performance of the connection, the steel tube yield strength and the ratio of upper and lower column stiffness should be efficiently controlled in the design of antique buildings’ USCFST-LCCFST column connection components.
Recycling of Plastic Polymer: Reinforcement of Building Material Using Polymer Plastics of Used COVID-19 Syringes
Authors: Fahim Golam , Hossain Md. Tofazzal , Penheiro Stapheny , Zakir Md. Iffat Bin , Shamsuzzaman Md. , Morshed Mohammad Sarwar , Khan Sakib Hossain , Hamja Abu
Published: March 2023

Plastic waste causes severe environmental impacts worldwide and threatens the lives of all creatures. In the medical field, most of the equipment, especially personal protective equipment (PPE), is made from single-use plastic. During COVID-19, the usage of PPE has increased, and is disposed of in landfills after being used once. Worldwide, millions of tons of waste syringes are generated from COVID-19 vaccination. A practical alternative to utilizing this waste is recycling it to reinforce building materials. This research introduces an approach to using COVID-19 syringe plastic waste to reinforce building material as composite concrete. Reinforced fiber polymer (FRP) concrete materials were used to mold cylindrical specimens, which underwent mechanical tests for mechanical properties. This study used four compositions with 0%, 5%, 10%, and 15% of FRP to create cylindrical samples for optimum results. Sequential mechanical tests were carried out on the created samples. These specimens were cured for a long period to obtain water absorption capability. After several investigations, the highest tensile and compressive strengths, approximately 2.0 MPa and 10.5 MPa, were found for the 5% FRP composition samples. From the curing test, the lowest water absorbability of around 5% was found for the 5% FRP composition samples.
Preferences of Young Polish Renters: Findings from the Mediation Analysis
Authors: Sobieraj Janusz , Bryx Marek , Metelski Dominik
Published: March 2023

The worsening housing problems of young adults in many countries have become a worldwide problem. Researchers point to a number of factors that influence young people’s decisions to own or rent their own apartments or houses. The term generation of renters or the lost generation has appeared in the literature in relation to the young adult generation. This article offers insights into the housing preferences of young adults aged 18 to 45 in Poland, with a particular focus on the renter cohort. Conclusions are drawn about whether young adults who are already renting prefer to buy an apartment or house rather than maintain their status quo, and what determines their decisions in this regard. The study identifies a number of socioeconomic factors that influence the housing decisions of young renters in Poland. It addresses some of the problems and challenges of today’s housing market and, in particular, examines what leads young Polish renters to switch from renting to buying their first home or, alternatively, to live in a rented apartment for years (thus showing indifference to homeownership). Some of the reasons for the change in attitude toward this issue are highlighted. The study is quantitative in nature, relying on an online survey and a mediation analysis that is particularly well suited to explaining the relationship between many different variables. Of the eight hypotheses tested in the study (using mediation analysis), only three could be proven, namely that the amount of rent payments and other costs for economic reasons influences the willingness to buy an apartment or a house, and also that the length of the rental period has a negative influence on the willingness to buy a house. Finally, the mediation model provides evidence that the higher a young renter’s tolerance threshold for mortgage interest compared to “rent payments”, the more inclined they are to buy an apartment or house. The study suggests that the housing finance subsystem has some shortcomings as far as financing young people is concerned. Strategically, there are two complementary solutions that could be implemented: (1) a long-term home savings plan or program and (2) innovative housing loan options tailored to the financial situation of young people.
Evolutionary Game Analysis for Key Participants’ Behavior in Digital Transformation of the Chinese Construction Industry
Authors: Zhang Chaoyong , Lv Lelin , Wang Zhuofu
Published: March 2023

The transformation and upgrading of the construction industry has made obvious progress in China. However, the low degree of digitalization is still prominent. The digital transformation decision-making behavior of key participants in the construction industry is easily affected by economic interests, meaning that the implementation of digital transformation is a dynamic evolution process of repeated adjustment and continuous learning. Therefore, this study constructed a tripartite evolutionary game model of the government, service providers, and construction enterprises, and analyzed the strategy selection of each game player and the stability of the system equilibrium point. Moreover, the validity of the model and the influence of various factors on the system were verified and analyzed by numerical simulation. The results showed the following: (1) The government’s tax refund ratio and subsidy coefficient can significantly increase the motivation of construction enterprises and digital construction service providers within a certain threshold. (2) Whether enterprises carry out a comprehensive digital transformation depends on the revenue of the system solution strategy; the greater the revenue, the more positive the enterprises. (3) The adoption of high rewards and high penalties by the superior government can effectively encourage the local government to actively promote digital transformation. The contribution of this study lies in providing a theoretical basis and decision support for promoting the digital transformation of construction enterprises.
Non-Linear Analysis of Flat Slabs Prestressed with Unbonded Tendons Submitted to Punching Shear
Authors: Brigo Heraldo , Ashihara Luana J. , Marques Marília G. , Liberati Elyson A. P.
Published: March 2023

This article describes a numerical study for the evaluation of the punching shear behavior of non-adherent prestressed flat slabs without shear reinforcement. Nonlinear three-dimensional models were used, along with the finite element method (FEA) through the ATENA software in order to validate the constitutive models adopted for concrete and steel. The numerical results were compared with the experimental results. The results revealed a good agreement among load capacity, deformations, and cracking panorama, as well as the relation between numerical and experimental failure loads. After validation, a parametric study was carried out to analyze the influence of tendon spacing, slab thickness, and column rectangularity in prestressed flat slabs. Finally, the results obtained in the numerical models in relation to the failure load were compared with the estimated values for the failure load according to the main normative predictions dealing with the flat slab system.
Increased Local Testosterone Levels Alter Human Fallopian Tube mRNA Profile and Signaling
Authors: Russo Angela , Cain Brian P. , Jackson-Bey Tia , Lopez Carrero Alfredo , Miglo Jane , MacLaughlan Shannon , Isenberg Brett C. , Coppeta Jonathan , Burdette Joanna E.
Published: March 2023

Fallopian tube epithelium (FTE) plays a critical role in reproduction and can be the site where High Grade Serous Ovarian Carcinoma (HGSOC) originates. Tumorigenic oviductal cells, which are the murine equivalent of human fallopian tube secretory epithelial cells (FTSEC), enhance testosterone secretion by the ovary when co-cultured with the ovary, suggesting that testosterone is part of the signaling axis between the ovary and FTSEC. Furthermore, testosterone promotes proliferation of oviductal cells. Oral contraceptives, tubal ligation, and salpingectomy, which are all protective against developing ovarian cancer, also decrease circulating levels of androgen. In the current study, we investigated the effect of increased testosterone on FTE and found that testosterone upregulates wingless-type MMTV integration family, member 4 (WNT4) and induces migration and invasion of immortalized human fallopian tube cells. We profiled primary human fallopian tissues grown in the microfluidic system SOLO-microfluidic platform –(MFP) by RNA sequencing and found that p53 and its downstream target genes, such as paired box gene 2 (PAX2), cyclin-dependent kinase inhibitor 1A (CDK1A or p21), and cluster of differentiation 82 (CD82 or KAI1) were downregulated in response to testosterone treatment. A microfluidic platform, the PREDICT-Multi Organ System (PREDICT-MOS) was engineered to support insert technology that allowed for the study of cancer cell migration and invasion through Matrigel. Using this system, we found that testosterone enhanced FTE migration and invasion, which was reversed by the androgen receptor (AR) antagonist, bicalutamide. Testosterone also enhanced FTSEC adhesion to the ovarian stroma using murine ovaries. Overall, these results indicate that primary human fallopian tube tissue and immortalized FTSEC respond to testosterone to shift expression of genes that regulate invasion, while leveraging a new strategy to study migration in the presence of dynamic fluid flow.
Molecular Tailored Therapeutic Options for Advanced Gastrointestinal Stromal Tumors (GISTs): Current Practice and Future Perspectives
Authors: Catalano Fabio , Cremante Malvina , Dalmasso Bruna , Pirrone Chiara , Lagodin D’Amato Agostina , Grassi Massimiliano , Comandini Danila
Published: March 2023

Gastrointestinal stromal tumors (GISTs) are one of the most common mesenchymal tumors characterized by different molecular alterations that lead to specific clinical presentations and behaviors. In the last twenty years, thanks to the discovery of these mutations, several new treatment options have emerged. This review provides an extensive overview of GISTs’ molecular pathways and their respective tailored therapeutic strategies. Furthermore, current treatment strategies under investigation and future perspectives are analyzed and discussed.
Presence of Multi-Morbidities and Colorectal Cancer Screening Utilization among Breast Cancer Survivors
Authors: Tsai Meng-Han , Grunert Caitlyn , Vo Jacqueline B. , Moore Justin X. , Guha Avirup
Published: March 2023

Purpose: Our study aimed to examine the association between the presence of chronic diseases with guideline-concordant colorectal cancer (CRC) screening utilization among breast cancer survivors. Methods: We analyzed data among women with a history of breast cancer from the 2016, 2018, and 2020 Behavioral Risk Factor Surveillance System. Receipt of guideline-concordant CRC screening was the outcome of interest. Diabetes, coronary heart disease/myocardial infarction, stroke, chronic obstructive pulmonary disease, emphysema/chronic bronchitis, arthritis, depressive disorder, or kidney diseases were included in chronic disease conditions. Results: Among 1324 survivors, those with multi-morbidities (3+ chronic diseases; 88.3%) had higher CRC screening use compared to those with one (84.4%) or two (85.4%) diseases (p-value < 0.05). In multivariable analysis, survivors with multi-morbidities were two times more likely to have CRC screening compared to those with only one disease (OR, 2.10; 95% CI, 1.11–3.98). Among survivors with multi-morbidities, Black women (OR, 14.07; 95% CI, 5.61–35.27), and those with frequent poor physical health (OR, 3.32; 95% CI, 1.57–7.00) were positively associated with CRC screening use. Conversely, survivors with frequent poor mental health were 67% less likely to receive CRC screening (OR, 0.33; 95% CI, 0.14–0.74). Conclusion: Among breast cancer survivors, multi-morbidities were positively associated with CRC screening.
Semi-Supervised Learning to Automate Tumor Bud Detection in Cytokeratin-Stained Whole-Slide Images of Colorectal Cancer
Authors: Bokhorst John-Melle , Nagtegaal Iris D. , Zlobec Inti , Dawson Heather , Sheahan Kieran , Simmer Femke , Kirsch Richard , Vieth Michael , Lugli Alessandro , van der Laak Jeroen , Ciompi Francesco
Published: March 2023

Tumor budding is a histopathological biomarker associated with metastases and adverse survival outcomes in colorectal carcinoma (CRC) patients. It is characterized by the presence of single tumor cells or small clusters of cells within the tumor or at the tumor-invasion front. In order to obtain a tumor budding score for a patient, the region with the highest tumor bud density must first be visually identified by a pathologist, after which buds will be counted in the chosen hotspot field. The automation of this process will expectedly increase efficiency and reproducibility. Here, we present a deep learning convolutional neural network model that automates the above procedure. For model training, we used a semi-supervised learning method, to maximize the detection performance despite the limited amount of labeled training data. The model was tested on an independent dataset in which human- and machine-selected hotspots were mapped in relation to each other and manual and machine detected tumor bud numbers in the manually selected fields were compared. We report the results of the proposed method in comparison with visual assessment by pathologists. We show that the automated tumor bud count achieves a prognostic value comparable with visual estimation, while based on an objective and reproducible quantification. We also explore novel metrics to quantify buds such as density and dispersion and report their prognostic value. We have made the model available for research use on the grand-challenge platform.
Insights into Gold Nanoparticles Possibilities for Diagnosis and Treatment of the Head and Neck Upper Aerodigestive Tract Cancers
Authors: Andrade Lídia M. , Costa Guilherme M. J.
Published: March 2023

Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer affecting people and accounts for more than 300,000 deaths worldwide. Improvements in treatment modalities, including immunotherapy, have demonstrated promising prognoses for eligible patients. Nevertheless, the five-year overall survival rate has not increased significantly, and the tumor recurrence ratio remains at 50% or higher, except for patients with HPV-positive HNSCC. Over the last decades, nanotechnology has provided promising tools, especially for biomedical applications, due to some remarkable physicochemical properties of numerous nanomaterials, particularly gold nanoparticles. This review addresses the features and some applications of gold nanoparticles reported in the literature over the last five years regarding the diagnosis and treatment of head and neck cancer, highlighting the exciting possibilities of this nanomaterial in oncology. Methods: The scientific papers selected for this review were obtained from the PubMed Advanced, Web of Science, Scopus, ClinicalTrials.gov, and Google Scholar platforms. Conclusions: Results from papers applying gold nanoparticles have suggested that their application is a feasible approach to diagnostics, prognostics, and the treatment of HNC. Moreover, phase I clinical trials suggest that gold nanoparticles are safe and can potentially become theranostic agents for humans.
Precision Surgery of Colorectal Liver Metastases in the Current Era: A Systematic Review
Authors: Papaconstantinou Dimitrios , Pararas Nikolaos , Pikouli Anastasia , Nastos Constantinos , Charalampopoulos Anestis , Dellaportas Dionysios , Bagias George , Pikoulis Emmanouil
Published: March 2023

Liver resection for colorectal liver metastases (CRLM) is widely considered the treatment with the highest curative potential. However, not all patients derive the same oncological benefit, underlining the need for better patient stratification and treatment allocation. In this context, we performed a systematic review of the literature to determine the role of RAS status in selecting the optimal surgical strategy. Evidence comparing anatomical with non-anatomical resections depending on RAS mutational status was scarce and conflicting, with two studies reporting superiority in mutated RAS (mutRAS) patients and two studies reporting equivalent outcomes. The rate of incomplete microscopic resection (R1) was found to be increased among mutRAS patients, possibly due to higher micrometastatic spread lateral to the primary lesion. The impact of R1 resection margins was evaluated separately for mutRAS and wild-type patients in three studies, of which, two indicated an additive detriment to long-term survival in the former group. In the current era of precision surgery, RAS status can be utilized to predict the efficacy of liver resection in the treatment of CRLM, avoiding a potentially morbid operation in patients with adverse tumor profiles.
Psychosocial Impact of Virtual Cancer Care through Technology: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Caminiti Caterina , Annunziata Maria Antonietta , Di Giulio Paola , Isa Luciano , Mosconi Paola , Nanni Maria Giulia , Piredda Michela , Verusio Claudio , Diodati Francesca , Maglietta Giuseppe , Passalacqua Rodolfo
Published: March 2023

This meta-analysis of RCTs aimed to determine whether replacing face-to-face hospital care with telemedicine deteriorates psychosocial outcomes of adult cancer patients, in terms of quality of life (QoL), anxiety, distress, and depression. RCTs on interventions aimed at improving patient psychosocial outcomes were excluded. MEDLINE, EmBASE, and PsycInfo were searched on 13 May 2022 without language or date restrictions. In total, 1400 records were identified and 8 RCTs included (4434 subjects). Study methodological quality was moderate. Statistically significant improvements were observed in favor of the intervention for QoL (SMD = 0.22, 95% CI 0.01 to 0.43, p = 0.04), anxiety (SMD = −0.17, 95% CI −0.30 to −0.04, p < 0.01), and global distress (SMD = −0.38, 95% CI −0.51 to −0.25, p < 0.01). A meta-analysis on depression could not be performed. In subgroup analyses, the intervention appeared to be more beneficial for patients receiving active treatment vs. follow-up, for “other cancer types” vs. breast cancer, and for “other modes of administration” vs. telephone. Given the many potential advantages of being assisted at home, telemedicine appears to be a viable option in oncology. However, more research is necessary to determine the types of patients who may benefit the most from these alternative care modalities.
Proton or Carbon Ion Therapy for Skull Base Chordoma: Rationale and First Analysis of a Mono-Institutional Experience
Authors: Tubin Slavisa , Fossati Piero , Mock Ulrike , Lütgendorf-Caucig Carola , Flechl Birgit , Pelak Maciej , Georg Petra , Fussl Christoph , Carlino Antonio , Stock Markus , Hug Eugen
Published: March 2023

Background: Skull base chordomas are radio-resistant tumors that require high-dose, high-precision radiotherapy, as can be delivered by particle therapy (protons and carbon ions). We performed a first clinical outcome analysis of particle therapy based on the initial 4-years of operation. Methods: Between August 2017 and October 2021, 44 patients were treated with proton (89%) or carbon ion therapy (11%). Prior gross total resection had been performed in 21% of lesions, subtotal resection in 57%, biopsy in 12% and decompression in 10%. The average prescription dose was 75.2 Gy RBE in 37 fractions for protons and 66 Gy RBE in 22 fractions for carbon ions. Results: At a median follow-up of 34.3 months (range: 1–55), 2-, and 3-year actuarial local control rates were 95.5% and 90.9%, respectively. The 2-, and 3-year overall and progression-free survival rates were 97.7%, 93.2%, 95.5% and 90.9%, respectively. The tumor volume at the time of particle therapy was highly predictive of local failure (p < 0.01), and currently, there is 100% local control in patients with tumors < 49 cc. No grade ≥3 toxicities were observed. There was no significant difference in outcome or side effect profile seen for proton versus carbon ion therapy. Five patients (11.4%) experienced transient grade ≤2 radiation-induced brain changes. Conclusions: The first analysis suggests the safety and efficacy of proton and carbon ion therapy at our center. The excellent control of small to mid-size chordomas underlines the effectiveness of particle therapy and importance of upfront maximum debulking of large lesions.
The Effect of Risk-Reducing Salpingo-Oophorectomy on Breast Cancer Incidence and Histopathological Features in Women with a BRCA1 or BRCA2 Germline Pathogenic Variant
Authors: Stuursma Annechien , van der Vegt Bert , Jansen Liesbeth , Berger Lieke P. V. , Mourits Marian J. E. , de Bock Geertruida H.
Published: March 2023

Background: Risk-reducing salpingo-oophorectomy (RRSO) is advised for female BRCA1/2 germline pathogenic variant (GPV) carriers to reduce tubal/ovarian cancer risk. RRSO may also affect breast cancer (BC) incidence. The aim was to investigate the effect of RRSO on BC incidence and histopathological features in female BRCA1/2 GPV carriers. Methods: Prospectively collected clinical data from BRCA1/2 GPV carriers in our hospital-based data/biobank were linked to the Dutch Nationwide Pathology Databank (PALGA) in January 2022. Multivariable Cox-proportional hazard models were used to calculate hazard ratios (HRs) with 95% confidence intervals (95% CIs), where the pre-RRSO group was considered the reference group and the primary endpoint was the first primary BC. Histopathological features of BCs pre- and post-RRSO were compared using descriptive statistics. Results: In 1312 women, 164 incident primary BCs were observed. RRSO did not decrease BC risk for BRCA1 GPV (HR: 1.48, 95% CI: 0.91–2.39) or BRCA2 GPV (HR: 0.95, 95% CI: 0.43–2.07) carriers. BCs tended to be smaller post-RRSO (median: 12 mm) than pre-RRSO (15 mm, p: 0.08). There were no statistically significant differences in histopathological features. Conclusions: RRSO did not decrease BC risk or affect BC features in BRCA1/2 GPV in this study, although BCs diagnosed post-RRSO tended to be smaller.
Impact of Sex-Specific Preoperative Fat Mass Assessment on Long-Term Prognosis after Gastrectomy for Gastric Cancer
Authors: Matsui Ryota , Inaki Noriyuki , Tsuji Toshikatsu , Fukunaga Tetsu
Published: March 2023

We investigated the impact of the difference in fat distribution between men and women on long-term prognosis after gastrectomy in patients with advanced gastric cancer. Patients with advanced gastric cancer deeper than p-T2 who underwent gastrectomy between April 2008 and June 2018 were included. Visceral fat mass index (VFI) and subcutaneous fat mass index (SFI) were calculated by dividing the cross-sectional area at the umbilical level by the height squared. The medians of VFI and SFI by sex were defined as cut-off values, below which values were defined as low VFI and low SFI. Of the 485 patients, 323 (66.6%) were men and 162 (33.4%) were women. Men with a low VFI had a significantly worse overall survival (OS) (p = 0.004) and women with a low SFI had a significantly worse OS (p = 0.007). Patients with a low VFI and low SFI had the worst prognosis. Multivariate analysis showed that a low VFI was an independent poor prognostic factor in men, while a low SFI was an independent poor prognostic factor in women. In conclusion, a low visceral fat mass in men and a low subcutaneous fat mass in women were independent poor prognostic factors after radical gastrectomy for advanced gastric cancer.
Phase IIa Clinical Biomarker Trial of Dietary Arginine Restriction and Aspirin in Colorectal Cancer Patients
Authors: Zell Jason A. , Taylor Thomas H. , Albers C. Gregory , Carmichael Joseph C. , McLaren Christine E. , Wenzel Lari , Stamos Michael J.
Published: March 2023

After potentially curative treatment, colorectal cancer (CRC) patients remain at high risk for recurrence, second primary CRC, and high-risk adenomas. In combination with existing data, our previous findings provide a rationale for reducing tissue polyamines as tertiary prevention in non-metastatic CRC patients. The goal of this study was to demonstrate rectal tissue polyamine reduction in optimally treated stage I-III CRC patients after intervention with daily oral aspirin + dietary arginine restriction. A single-institution phase IIa clinical trial was conducted. Patients were treated with aspirin 325 mg/day and an individualized dietary regimen designed to reduce arginine intake by ≥30% over a 12-week study period. Dietary intake, endoscopy with rectal biopsies, and phlebotomy were performed pre- and post-intervention. The primary endpoint was to demonstrate ≥50% decrease in rectal tissue putrescine levels from baseline as a measure of polyamine reduction in the target tissue. Twenty eligible patients completed the study. After study intervention, mean dietary arginine intake decreased from 3.7 g/day ± 1.3 SD to 2.6 g/day ± 1.2 SD (29.7% decrease, p < 0.02 by Sign test). Mean plasma arginine levels decreased from 46.0 ng/mL ± 31.5 SD at baseline to 35 ng/mL ± 21.7 SD (p < 0.001). Rectal tissue putrescine levels were 0.90 nMol/mg-protein pre-intervention and 0.99 nMol/mg-protein post-intervention (p < 0.64, NS). No significant differences were observed for the other tissue polyamines investigated: spermidine (p < 0.13), spermine (p < 0.21), spermidine:spermine ratio (p < 0.71). Among CRC survivors, treatment with daily oral aspirin and an individualized dietary arginine restriction intervention resulted in lower calculated dietary arginine intake and plasma arginine levels but did not affect rectal tissue polyamine levels.
Sodium-Glucose Cotransporter-2 Inhibitor versus Beta-Blocker Use for Hepatocellular Carcinoma Risk among People with Hepatitis B or C Virus Infection and Diabetes Mellitus
Authors: Hu Wei-Syun , Lin Cheng-Li
Published: March 2023

Objective: The current study detects the effect of sodium-glucose cotransporter-2 inhibitor (SGLT2I) versus beta-blocker (BB) in diabetes mellitus (DM) with chronic hepatitis B or C on hepatocellular carcinoma (HCC) outcomes. Methods: The multivariate logistic regression model, including all baseline characteristics and index year, was used to calculate the propensity scores, and we performed the greedy algorithm on propensity scores to create matched pairs of SGLT2I and BB users. Hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) of HCC were estimated by Cox proportional hazards regression models, and we adjusted for confounding factors by including the baseline characteristics in the regression models. Results: After matching in a ratio of 1:1, 7023 SGLT2I users and 7023 BB users were included in the following statistical analyses. The overall HRs showed a significantly lower risk of HCC in SGLT2I users in comparison to a reference group of BB users with an adjusted HR of 0.27 (0.21, 0.34). Conclusions: Compared to BB use, SGLT2I was associated with a significant risk reduction in HCC occurrence.
New Perspectives on Primary Prophylaxis of Invasive Fungal Infection in Children Undergoing Hematopoietic Stem Cell Transplantation: A 10-Year Retrospective Cohort Study
Authors: Ricard Noémi , Zebali Lelia , Renard Cécile , Goutagny Marie-Pierre , Benezech Sarah , Bertrand Yves , Philippe Michael , Domenech Carine
Published: March 2023

Background: Allogenic hematopoietic stem cell transplantation (a-HCT) remains a therapeutic treatment for many pediatric hematological diseases. The occurrence of invasive fungal infections (IFIs) is a complication for which ECIL-8 recommends primary antifungal prophylaxis. In this study, we evaluated the impact of our local strategy of not systematically administering primary antifungal prophylaxis in children undergoing a-HCT on the occurrence and mortality of IFIs. Methods: We performed a retrospective monocentric study from 2010 to 2020. We retained all proven and probable IFIs diagnosed during the first year post a-HCT. Results: 308 patients were included. Eighteen patients developed twenty IFIs (thirteen proven, seven probable) (6.5%) among which aspergillosis (n = 10, 50%) and candidosis (n = 7, 35%) were the most frequently diagnosed infections. Only 2% of children died because of an IFI, which represents 14% of all deaths. Multivariate analysis found that age > 10 years (OR: 0.29), the use of a therapeutic antiviral treatment (OR: 2.71) and a low neutrophil count reconstitution (OR: 0.93) were significantly associated with the risk of IFI occurrence. There was also a trend of malignant underlying disease and status ≥ CR2 but it was not retained in multivariate analysis. Conclusions: IFI occurrence was not higher in our cohort than what is reported in the literature with the use of systematic antifungal prophylaxis, with a good survival rate nonetheless. Thus, a prophylaxis could be considered for children with a high risk of IFI such as those aged over 10 years.