bluuebunny/crossref_metadata_2025 huggingface dataset:
Pressure Vessel Design Problem Using Improved Gray Wolf Optimizer Based on Cauchy Distribution
Authors: Li Jun , Sun Kexue
Published: November 2023

The Gray Wolf Optimizer (GWO) is an established algorithm for addressing complex optimization tasks. Despite its effectiveness, enhancing its precision and circumventing premature convergence is crucial to extending its scope of application. In this context, our study presents the Cauchy Gray Wolf Optimizer (CGWO), a modified version of GWO that leverages Cauchy distributions for key algorithmic improvements. The innovation of CGWO lies in several areas: First, it adopts a Cauchy distribution-based strategy for initializing the population, thereby broadening the global search potential. Second, the algorithm integrates a dynamic inertia weight mechanism, modulated non-linearly in accordance with the Cauchy distribution, to ensure a balanced trade-off between exploration and exploitation throughout the search process. Third, it introduces a Cauchy mutation concept, using inertia weight as a probability determinant, to preserve diversity and bolster the capability for escaping local optima during later search phases. Furthermore, a greedy strategy is employed to incrementally enhance solution accuracy. The performance of CGWO was rigorously evaluated using 23 benchmark functions, demonstrating significant improvements in convergence rate, solution precision, and robustness when contrasted with conventional algorithms. The deployment of CGWO in solving the engineering challenge of pressure vessel design illustrated its superiority over traditional methods, highlighting its potential for widespread adoption in practical engineering contexts.
Characterization of the Migration of Soil Particles in Lateritic Soils under the Effect of Rainfall
Authors: Cao Dezhi , A Fayou , Li Yong , Yang Taiqiang , Liao Qingsong
Published: November 2023

Rainfall is the main cause of erosion damage in loose slope deposits. During rainfall infiltration, fine particles in the soil mass will move with water infiltration, thus changing the localized particle distribution of the soil mass, which, in turn, causes changes in the pore water pressure and volumetric water content within the slope and ultimately affects slope stability. In order to develop advanced soil and water conservation programs to prevent slope damage, it is crucial to understand and accurately reproduce the particle migration and aggregation characteristics of soils under different rainfall conditions. Therefore, this paper systematically investigates the soil particle migration characteristics of the soil body under rainfall conditions by simulating the internal erosion of the lateritic soil slope body under rainfall conditions via slope internal erosion simulation experiments and experimentally analyzing the migration and aggregation of fine particles in the slope body, as well as the changed rules regarding pore water pressure and volumetric water content at different locations of the slope body with rainfall. The results of this study show that (1) with the infiltration of rainfall, the fine particles in the slope body mainly infiltrate in the vertical direction in an early stage of rainfall; in a later stage, there is vertical downward and down-slope seepage. Therefore, fine particles always gather at the toe of the slope, which leads to relatively high water content and pore water pressure at the toe of the slope, and thus, the slope is always damaged from the toe of the slope. (2) Inside the slope, the fine particles always gather at the smallest pore diameter. With the enhancement of hydrodynamic force, they will be lost again, which leads to a sudden decrease in the local volumetric water content of the slope, and the pore space increases. Then, it is filled with seepage water, which makes the pore water pressure fluctuate or increase. (3) Based on the particle distribution parameter, the present study produced a distribution map of the fine particle content of the slope body under different rainfall intensities and established a model of the dynamic change of fine particles, which improves the understanding of the effect of the change in the fine particle composition of the slope body on the water content and the pore water pressure and may be helpful for the assessment of the initiation of the mudslides.
Stress Corrosion Cracking Analysis of a Hot Blast Stove Shell with an Internal Combustion Chamber
Authors: Park Donghwi , Guo Feng , Kim Naksoo
Published: November 2023

The stress corrosion cracking during the operation of the internal combustion hot blast stove was analysed. The computational fluid dynamics and finite element analysis models were established to analyse the temperature, stress and other variables related to the condensation of the water and acids. The corrosion characteristics of condensation of acid and the stress corrosion cracking of the metallic shell of the hot blast stove during the operation were predicted by applying the fluid temperature and mapping it to the solid temperature. The stress corrosion cracking surface mobility mechanism was adopted and modified with a weight concept to consider the effect of the acid condensation and its concentration. The regions that have higher crack propagation rates were analysed. The influence of the increase in the blast temperature on the crack propagation rate was studied with the increase in the blast temperature by 45 K and 90 K from the reference blast temperature. The maximum temperature of the refractory linings was 1847 K in the on-gas period, and the maximum change in the shell temperature was 5.2 K when the blast temperature was increased by 90 K. The maximum crack propagation rate for the reference blast temperature was evaluated as 7.61×10−7 m/s. The maximum value of the crack propagation rate was increased by 16.7% when the blast temperature increased by 90 K. The conical region was found to have higher crack propagation rates, which means that the conical region should be the region of interest for managing the internal combustion hot blast stoves.
Performance of Unreinforced Masonry Walls in Compression: A Review of Design Provisions, Experimental Research, and Future Needs
Authors: Blash Abrahem A. Ali , Bakar B. H. Abu , Udi Ufuoma Joseph , Dabbour Bassam S. A. , Jaafar Azhar Ayad , Yanhao Li , Abu Bakar Ilyani Akmar , Rashed Majed
Published: November 2023

Unreinforced masonry (URM) is a construction of brick or concrete block unit that is joined together using mortar, without steel reinforcement. Because of the heterogeneous nature and difference in mechanical properties of the masonry elements, analyzing and capturing the structural behaviour of URM walls under various loading conditions is therefore complex. In recent decades, research efforts have been focused on addressing and understanding the compressive behaviour of URM walls from the experimental viewpoint. However, from the existing experimental literature, there is a significant degree of variation in the mechanical and geometric properties of URM walls, especially the comprehensive comparison of apparently equivalent test parameters, which has yet to be examined. It is therefore necessary to highlight and critically examine major results derived from the experimental literature to better understand the performance of URM walls under compressive loads. This review paper presents the assessment performance with regard to axial compressive tests on URM walls, along with comprehensive comparisons among the experimental literature findings on the basis of masonry construction methods and various influencing parameters. Emphasis in the literature has been placed chiefly on the masonry elements, design provisions, axial load, slenderness ratio, openings, and stress–strain response. Based on observations from the study, experimental development trends have been highlighted to identify and outline potential directions for future studies.
Information Communication Technology (ICT) and Education
Authors: Balaban Igor , Rienties Bart , Winne Philip H.
Published: November 2023

COVID-19 has accelerated the shift to blended or fully online learning environments, enforcing educational institutions to embrace technology and offer their students an online or at least blended learning experience [...]
Novel Method for Ranking Generalized Fuzzy Numbers Based on Normalized Height Coefficient and Benefit and Cost Areas
Authors: Le Thi Hong Phuong , Chu Ta-Chung
Published: November 2023

This paper proposes a method for ranking generalized fuzzy numbers, which guarantees that both horizontal and vertical values are important parameters affecting the final ranking score. In this method, the normalized height coefficient is introduced to evaluate the influence of the height of fuzzy numbers on the final ranking score. The higher the normalized height coefficient of a generalized fuzzy number is, the higher its ranking. The left and right areas are presented to calculate the impact of the vertical value on the final ranking score. The left area is considered the benefit area. The right area is considered the cost area. A generalized fuzzy number is preferred if the benefit area is larger and the cost area is smaller. The proposed method can be employed to rank both normal and non-normal fuzzy numbers without normalization or height minimization. Numerical examples and comparisons with other methods highlight the feasibility and robustness of the proposed method, which can overcome the shortcomings of some existing methods and can support decision-makers in selecting the best alternative.
Intracranial Aneurysms and Lipid Metabolism Disorders: From Molecular Mechanisms to Clinical Implications
Authors: Pan Tonglin , Shi Yuan , Yu Guo , Mamtimin Abdureshid , Zhu Wei
Published: November 2023

Many vascular diseases are linked to lipid metabolism disorders, which cause lipid accumulation and peroxidation in the vascular wall. These processes lead to degenerative changes in the vessel, such as phenotypic transformation of smooth muscle cells and dysfunction and apoptosis of endothelial cells. In intracranial aneurysms, the coexistence of lipid plaques is often observed, indicating localized lipid metabolism disorders. These disorders may impair the function of the vascular wall or result from it. We summarize the literature on the relationship between lipid metabolism disorders and intracranial aneurysms below.
Unveiling the Mechanisms through Which Leader Integrity Shapes Ethical Leadership Behavior: Theory of Planned Behavior Perspective
Authors: Mohi Ud Din Qaiser , Zhang Li
Published: November 2023

Leadership integrity is crucial in shaping ethical leadership or promoting a rigorous adherence to moral principles and standards. This study explores the intricate relationship between leader integrity, moral identification, self-regulation, and ethical leadership behavior, providing practical insights for healthcare leaders seeking to enhance ethical practices. It addresses a critical gap in the research landscape by focusing on individual-level ethical leadership within the healthcare sector, where prior investigations have been limited. This study examines the mediating role of moral identification among leader integrity and ethical leadership behavior. We surveyed 181 health sector workers and employed SmartPLS to assess the conceptualized relationships. The analyses reveal a significant indirect influence of leader integrity on ethical leadership behavior, whereas moral identification mediates the relationship. Our findings further indicate an intriguing moderation effect of self-regulation on the relationship between moral identification and ethical leadership behavior. This divergence from previous research underscores the significance of contextual and methodological factors in studying leadership integrity and ethical behavior. Our study contributes to the literature on the relationship through planned behavior theory by demonstrating that moral identification mediates the relationship between leader integrity and ethical leadership behavior in the context of the theory of planned behavior. Our findings underscore the significance of fostering leader integrity within organizations to indirectly promote ethical leadership behaviors through moral identification. Organizations should prioritize initiatives that cultivate moral identification among their members to enhance ethical cultures.
Numerical Analysis of the Influence of Deep Excavation on Nearby Pile Foundation Building
Authors: Wang Kai , Yang Zheng , Guo Jianghao , Dang Yike , Yan Yuanling
Published: November 2023

In this paper, a numerical simulation is used to establish a three-dimensional model, which considers the height of buildings, the relative position between buildings, and foundation pits. These were studied in detail to investigate the changes in settlement of adjacent buildings and the displacement and internal force of piles caused by deep foundation pit excavation. The results indicate that the number of floors in the building, along with the angle and distance between the building and the excavation pit, have a significant impact on the settlement of the building and the deformation and internal force variation in the piles. For example, when D = 0.1 H, with the increase in the number of floors, the increase in the bending moment of pile 1 at the pile shaft is 62.63 kN·m, and the increase in the bending moment at the pile head is 224.72 kN·m. At this point, the maximum horizontal displacement of the pile shaft occurs at approximately 1.27 H. When θ = 45∘, the maximum difference between the maximum and minimum deformations of the building is 9.71 mm. When D ≤ 1.0 H, the majority of the building is in the primary influence range of surface settlement behind the wall, and the building undergoes a combined deformation of ‘upper convex’ and ‘concave’. When D > 1.0 H, the building predominantly resides in the secondary influence range, and the building undergoes a deformation of ‘upper convex’.
Preliminary Study on the Emission Dynamics of TVOC and Formaldehyde in Homes with Eco-Friendly Materials: Beyond Green Building
Authors: Jung Chuloh , Abdelaziz Mahmoud Naglaa Sami , Al Qassimi Nahla , Elsamanoudy Gamal
Published: November 2023

This preliminary study investigates the emission characteristics of formaldehyde (HCHO) and total volatile organic compounds (TVOC) in indoor environments, comparing the effects of eco-friendly materials and general materials. The study analyzes the concentration changes over time in the living rooms of experimental units to assess the effectiveness of eco-friendly materials in reducing indoor air pollutants. The results show that eco-friendly materials exhibit lower initial emissions of TVOC than general materials, gradually decreasing over time. Compared to the eco-friendly material unit, the general material unit takes longer to reach acceptable TVOC concentrations. The emission pattern of HCHO differs from TVOC, with the highest peak occurring on the seventh day. Major individual VOCs, except for benzene, exhibit a similar decreasing trend for TVOC over time. Eco-friendly materials demonstrate significant reductions in emissions compared to general materials in various material applications, including parquet flooring, wallpaper, built-in furniture, and kitchen furniture. However, the difference in emissions for door and window frames using eco-friendly materials is minimal. These findings emphasize the effectiveness of eco-friendly materials in reducing indoor air pollutants and provide valuable insights for creating healthier living environments. Further research is needed to optimize the application of eco-friendly materials in specific components and investigate their long-term impact on indoor air quality and occupant health.
Global Resistance Methods for the Design of Fiber-Reinforced Concrete (FRC) Beams with Material Nonlinear Finite Element Analysis
Authors: Shahrbijari Kamyar B. , Barros Joaquim A. O. , Valente Isabel B.
Published: November 2023

This article explores the application of the global resistance methods (GRMs) on the design of hybrid glass fiber-reinforced polymer (GFRP) and steel fiber-reinforced concrete (SFRC) beams. Addressing challenges posed by GFRP-reinforced beams, this study aims to assess the impact of material uncertainties on the behavior of such hybrid beams. The investigation involves the experimental testing of I-shaped SFRC beams, which are used to develop and validate nonlinear finite element analysis (NLFEA) models. These models incorporate material non-linearities while minimizing uncertainties related to modeling assumptions. Through the application of GRM, the study evaluates the global resistance safety factor, offering insights into the structural performance of hybrid reinforcement SFRC beams. Ultimately, this research seeks to facilitate a transition from traditional localized approaches to more accurate and comprehensive analyses for the design of hybrid reinforcement SFRC beams, contributing to the advancement of structural engineering by promoting safer, more resilient, and sustainable construction systems.
Contribution of Carbon Concrete Construction to the Circular and Resource Economy
Authors: Kortmann Jan , Minar Stefan
Published: November 2023

Fibre-reinforced composites are used in many industries. In the construction industry, for example, the building material carbon concrete is increasingly being used successfully. Although the demand for fibre-reinforced composites and fibre-reinforced plastics made of carbon fibres has risen continuously by approximately 11% per year over the last 10 years, there is currently still no coherent integration of fibre-containing waste into the corresponding material cycles. In addition, there are ever-increasing requirements for environmental and climate protection, which necessitate a transformation from linear waste management to a cycle-oriented recycling and resource management overall. Carbon concrete construction is already providing an important impetus for the construction industry. The use of reinforcement made of mat or grid-shaped and bar-shaped carbon fibres basically makes a significant contribution to the conservation of resources, and ultimately a reduction in CO2 emissions of up to 80% is possible. In connection with recyclability, it is demonstrated that with today’s common facilities, both the deconstruction and dismantling of components and structures made of carbon concrete and the collection and sorting of the demolition material using camera-based sorting with a grade purity of 98% are already possible. In addition, the article provides an outlook on the project WIRreFa|WIR! recyceln Fasern (We recycle fibres) and its approach to closing the material cycle of fibre composites.
Leukemia Cutis—The Current View on Pathogenesis, Diagnosis, and Treatment
Authors: Robak Ewa , Braun Marcin , Robak Tadeusz
Published: November 2023

Leukemia cutis (LC) is defined as the leukemic infiltration of the epidermis, the dermis, and the subcutaneous tissue. Leukemia cutis may follow or occur simultaneously with the diagnosis of systemic leukemia. However, cutaneous lesions are occasionally diagnosed as the primary manifestation of leukemia. Leukemic skin infiltrations demonstrate considerable variation regarding a number of changes, distribution, and morphology. The highest incidence of LC is observed in chronic lymphocytic leukemia, monocytic and myelomonocytic acute myeloid leukemia, and T-cell lineage leukemia. Although the pathogenic mechanism of the invasion of leukemic cells into the skin is not well understood, chemokine receptors and adhesion molecules as well as the genetic characteristics of leukemia are thought to play a role. Leukemic skin lesions may be localized or disseminated and may occur alone or in combination on any site of the skin, most frequently in the trunk and extremities. The most common clinical presentations of leukemia cutis are papules, nodules, macules, plaques, and ulcers. In most patients, the complete or partial resolution of cutaneous infiltrations occurs simultaneously with hematologic remission. However, in patients with resistant disease or recurrent skin infiltration, local radiotherapy can be used. This review presents recent data on the pathogenesis, diagnosis, and treatment of leukemic skin involvement in different types of leukemia.
Changing Trends in B-Cell Non-Hodgkin Lymphoma Treatment: The Role of Novel Monoclonal Antibodies in Clinical Practice
Authors: Tavarozzi Rita , Zacchi Giulia , Pietrasanta Daniela , Catania Gioacchino , Castellino Alessia , Monaco Federico , Gandolfo Carolina , Rivela Paolo , Sofia Antonella , Schiena Noemi , Bertassello Claudia , Limberti Giulia , Zallio Francesco , Zanni Manuela , Ladetto Marco
Published: November 2023

We are currently witnessing a dramatic shift in our approach to the treatment of B-cell non-Hodgkin lymphoma (B-NHL). In the evolving clinical landscape, novel treatments for this clinically heterogeneous disease span a wide range of interventions, encompassing targeted agents, cell therapy approaches, and novel monoclonal antibodies (NMABs). Among these, the latter are likely to exert the most profound impact due to their distinctive high efficacy and versatile applicability. NMABs represent a heterogeneous group of agents, including naked antibodies, immunotoxins, and T-cell-engaging molecules. In recent times, several NMABs have either gained regulatory approval or are on the verge of introduction into clinical practice, addressing multiple therapeutic indications and treatment regimens. Their anticipated impact is expected to be broad, initially in the context of relapsed/refractory (R/R) disease and subsequently extending to early treatment lines. The scope of this review is to provide a comprehensive overview of the biological characteristics, clinical properties, efficacy, and toxicity profiles of NMABs that have recently been introduced or are nearing integration into clinical practice.
Clinical PD-1/PD-L1 Blockades in Combination Therapies for Lymphomas
Authors: Katsuya Hiroo , Suzumiya Junji , Kimura Shinya
Published: November 2023

Immunotherapy with the programmed cell death protein 1 (PD-1)/PD-1 ligand (PD-L1) blockade has revolutionized the treatment of advanced solid cancers. However, these clinical benefits have been limited to cases of malignant lymphomas, showing promising results for only classic Hodgkin lymphoma (cHL) and primary mediastinal B-cell lymphoma (PMBCL). To bring clinical benefits to more patients with lymphoma, numerous combination therapies involving PD-1/PD-L1 blockade have been tested in clinical trials in both frontline and relapsed/refractory settings. This article reviews the current landscape of combination therapies with PD-1/PD-L1 blockade for lymphoma and discusses the potential therapeutic approaches. An interim analysis of a phase 3 study demonstrated increased progression-free survival with nivolumab combination therapy over the current frontline treatment in patients with advanced-stage cHL. The results of combination therapies for aggressive B-cell lymphomas, except for PMBCL, have been disappointing. Several clinical trials of combined PD-1/PD-L1 blockade and Bruton’s tyrosine kinase inhibitors are exploring its efficacy in patients with chronic lymphocytic leukemia (CLL) with Richter transformation. Several T-cell lymphoma subtypes respond to PD-1/PD-L1 blockade monotherapy. Further clinical trials are underway to investigate appropriate combination regimens with PD-1/PD-L1 blockade, especially for cHL, CLL with Richter transformation, and T-cell lymphoma, in both frontline and relapsed/refractory settings.
Harnessing 3D-CT Simulation and Planning for Enhanced Precision Surgery: A Review of Applications and Advancements in Lung Cancer Treatment
Authors: Hamanaka Kazutoshi , Miura Kentaro , Eguchi Takashi , Shimizu Kimihiro
Published: November 2023

The clinical application of three-dimensional computed tomography (3D-CT) technology has rapidly expanded in the last decade and has been applied to lung cancer surgery. Two consecutive reports of large-scale prospective clinical trials from Japan and the United States have brought a paradigm shift in lung cancer surgery and may have led to a rapid increase in sublobar lung resections. Sublobar resection, especially segmentectomy, requires a more precise understanding of the anatomy than lobectomy, and preoperative 3D simulation and intraoperative navigation support it. The latest 3D simulation software packages are user-friendly. Therefore, in this narrative review, we focus on recent attempts to apply 3D imaging technologies, particularly in the sublobar resection of the lung, and review respective research and outcomes. Improvements in CT accuracy and the use of 3D technology have advanced lung segmental anatomy. Clinical applications have enabled the safe execution of complex sublobar resection through a minimally invasive approach, such as video-assisted thoracoscopic surgery and robotic surgery. However, currently, many facilities still render 3D images on two-dimensional monitors for usage. In the future, it will be challenging to further spread and advance intraoperative navigation through the application of 3D output technologies such as extended reality.
Role of Immunotherapy in Gastroesophageal Cancers—Advances, Challenges and Future Strategies
Authors: Lynch Emer , Duffy Austin G. , Kelly Ronan J.
Published: November 2023

Background: Gastroesophageal cancers (GECs) carry considerable morbidity and mortality, and demonstrate geographical histological variances in addition to molecular heterogeneity. Consequently, the immunogenicity of the different subtypes, which can predict the likelihood of immunotherapy response, can vary. Immune checkpoint inhibitor (ICI) therapy has transformed the treatment of many cancer types over the past decade but has been slower to gain a foothold in the treatment paradigm of GECs. Methods: This article reviews the existing evidence and use approvals for immunotherapies and immune-based treatments in GECs, in the neoadjuvant, adjuvant and metastatic disease settings. The challenges of and limitations to ICI application in current clinical practice are examined. Ongoing clinical trials and future directions of research are also considered. Conclusion: ICI therapy has become an established treatment option within GECs, both perioperatively and in advanced disease. However, nuances in terms of its use are not yet fully understood. Ongoing research proposes to broaden the application of immunotherapies in GECs with the potential to continue to improve outcomes.
Stereotactic Radiosurgery of Multiple Brain Metastases: A Review of Treatment Techniques
Authors: Bodensohn Raphael , Maier Sebastian H. , Belka Claus , Minniti Giuseppe , Niyazi Maximilian
Published: November 2023

The advancement of systemic targeted treatments has led to improvements in the management of metastatic disease, particularly in terms of survival outcomes. However, brain metastases remain less responsive to systemic therapies, underscoring the significance of local interventions for comprehensive disease control. Over the past years, the threshold for treating brain metastases through stereotactic radiosurgery has risen. Yet, as the number of treated metastases increases, treatment complexity and duration also escalate. This trend has made multi-isocenter radiosurgery treatments, such as those with the Gamma Knife, challenging to plan and lengthy for patients. In contrast, single-isocenter approaches employing linear accelerators offer an efficient and expeditious treatment option. This review delves into the literature, comparing different linear-accelerator-based techniques with each other and in relation to dedicated systems, focusing on dosimetric considerations and feasibility.
Efficacy of Radiomics in Predicting Oncologic Outcome of Liver-Directed Combined Radiotherapy in Locally Advanced Hepatocellular Carcinoma
Authors: Park Jong Won , Lee Hansang , Hong Helen , Seong Jinsil
Published: November 2023

Purpose: We investigated whether radiomic features extracted from three-phase dynamic contrast-enhanced computed tomography (CECT) can be used to predict clinical outcomes, including objective treatment response (OR) and in-field failure-free survival rate (IFFR), in patients with hepatocellular carcinoma (HCC) who received liver-directed combined radiotherapy (LD-CRT). Methods: We included 409 patients, and they were randomly divided into training (n = 307) and validation (n = 102) cohorts. For radiomics models, we extracted 116 radiomic features from the region of interest on the CECT images. Significant clinical prognostic factors are identified to predict the OR and IFFR in the clinical models. We developed clinical models, radiomics models, and a combination of both features (CCR model). Results: Among the radiomic models evaluated for OR, the OR-PVP-Peri-1cm model showed favorable predictive performance with an area under the curve (AUC) of 0.647. The clinical model showed an AUC of 0.729, whereas the CCR model showed better performance (AUC 0.759). For the IFFR, the IFFR-PVP-Peri-1cm model showed an AUC of 0.673, clinical model showed 0.687, and the CCR model showed 0.736. We also developed and validated a prognostic nomogram based on CCR models. Conclusion: In predicting the OR and IFFR in patients with HCC undergoing LD-CRT, CCR models performed better than clinical and radiomics models. Moreover, the constructed nomograms based on these models may provide valuable information on the prognosis of these patients.
Therapeutic Efficacy and Safety of Lenvatinib after Atezolizumab Plus Bevacizumab for Unresectable Hepatocellular Carcinoma
Authors: Yano Shigeki , Kawaoka Tomokazu , Yamasaki Shintaro , Johira Yusuke , Kosaka Masanari , Shirane Yuki , Miura Ryoichi , Amioka Kei , Naruto Kensuke , Yamaoka Kenji , Fujii Yasutoshi , Uchikawa Shinsuke , Fujino Hatsue , Ono Atsushi , Nakahara Takashi , Murakami Eisuke , Miki Daiki , Tsuge Masataka , Teraoka Yuji , Kouno Hirotaka , Takaki Shintaro , Mori Nami , Tsuji Keiji , Oka Shiro
Published: November 2023

A total of 137 HCC patients treated with atezolizumab plus bevacizumab from October 2020 to September 2022 were enrolled. The median overall survival (OS) and progression-free survival (PFS) from the beginning of atezolizumab plus bevacizumab were 21.1 months (range, 18.8 months–not reached) and 10.5 months (range, 8.2–12.1 months), respectively. Fifty patients were diagnosed with progressive disease after atezolizumab plus bevacizumab. Of this group, 24 patients were administered lenvatinib, and the median OS and PFS from the beginning of lenvatinib were 15.3 months (range, 10.5 months–not reached) and 4.0 months (range, 2.5–6.4 months), respectively. The objective response rates based on the response evaluation criteria in solid tumors (RECISTs) criteria version 1.1 and modified RECISTs were 33.3% and 54.2%, respectively. There was no significant difference in the median serum alpha-fetoprotein level between before and after lenvatinib. In the multivariate analysis, Child–Pugh class A (hazard ratio 0.02, 95% confidence interval (CI) 0.02–0.76, p = 0.02) and intrahepatic tumor occupancy rate < 50% (hazard ratio < 0.01, 95% CI 0.003–0.35, p < 0.01) were the significant factors for OS. There were some frequent adverse events (AEs) in patients treated with lenvatinib such as hypertension, fatigue, anorexia, proteinuria, and so on, but none directly caused death. In conclusion, lenvatinib after atezolizumab plus bevacizumab for unresectable HCC should be considered an effective treatment option.
Treatment of Acute Myeloid Leukemia in Older Adults
Authors: Alsouqi Aseel , Geramita Emily , Im Annie
Published: November 2023

Acute Myeloid Leukemia (AML) is an aggressive myeloid malignancy predominantly affecting older adults. Despite the advancements in new therapies for AML, older and medically unfit patients continue to suffer from poor outcomes due to disease-related factors such as the mutational profile and patient-related factors such as comorbidities and performance status. In this review, we discuss a spectrum of therapeutic options for older patients with AML starting with a historical perspective and ending with therapies being investigated in clinical trials. We review the standard of care treatment options including combination venetoclax and hypomethylating agents, in addition to targeted therapies such as FLT3 and IDH inhibitors. Lastly, we shed light on challenges facing the care of older adults and their representation in clinical trials.
DanioCTC: Analysis of Circulating Tumor Cells from Metastatic Breast Cancer Patients in Zebrafish Xenografts
Authors: Reinhardt Florian , Coen Luisa , Rivandi Mahdi , Franken André , Setyono Eunike Sawitning Ayu , Lindenberg Tobias , Eberhardt Jens , Fehm Tanja , Niederacher Dieter , Knopf Franziska , Neubauer Hans
Published: November 2023

Circulating tumor cells (CTCs) serve as crucial metastatic precursor cells, but their study in animal models has been hindered by their low numbers. To address this challenge, we present DanioCTC, an innovative xenograft workflow that overcomes the scarcity of patient-derived CTCs in animal models. By combining diagnostic leukapheresis (DLA), the Parsortix microfluidic system, flow cytometry, and the CellCelector setup, DanioCTC effectively enriches and isolates CTCs from metastatic breast cancer (MBC) patients for injection into zebrafish embryos. Validation experiments confirmed that MDA-MB-231 cells, transplanted following the standard protocol, localized frequently in the head and blood-forming regions of the zebrafish host. Notably, when MDA-MB-231 cells spiked (i.e., supplemented) into DLA aliquots were processed using DanioCTC, the cell dissemination patterns remained consistent. Successful xenografting of CTCs from a MBC patient revealed their primary localization in the head and trunk regions of zebrafish embryos. DanioCTC represents a major step forward in the endeavors to study the dissemination of individual and rare patient-derived CTCs, thereby enhancing our understanding of metastatic breast cancer biology and facilitating the development of targeted interventions in MBC. Summary statement: DanioCTC is a novel workflow to inject patient-derived CTCs into zebrafish, enabling studies of the capacity of these rare tumor cells to induce metastases.
Extracranial Germ Cell Tumors in Children: Ten Years of Experience in Three Children’s Medical Centers in Shanghai
Authors: Jiang Shayi , Dong Kuiran , Li Kai , Liu Jiangbin , Du Xin , Huang Can , Jiao Yangyang , Han Yali , Yang Jingwei , Liao Xuelian , Li Yanhua , Zhang Ting , Li Shanshan , Lv Zhibao , Gao Yijin
Published: November 2023

Objective: The aim was to describe the clinical features of extracranial germ cell tumors (GCTs) in pediatrics and study the clinical risk factors related to survival for malignant germ cell tumors (MGCTs) in order to optimize therapeutic options. Methods: The clinical data of children with extracranial GCTs in three children’s medical centers in Shanghai were retrospectively analyzed. Results: In total, 1007 cases of extracranial GCTs diagnosed between 2010 and 2019 were included in this study, including teratomas (TERs) 706 (70.11%) and MGCTs 301 (29.89%). There were twice as many TER cases as MGCT cases. Approximately 50% of children with GCTs were <3 years old (43.39% for TERs, 67.13% for MGCTs). GCTs in children of different ages show differences in tumor anatomical locations and pathological subtypes. The 5-year event-free survival (EFS) and overall survival (OS) of all patients with MGCTs were 82.33% (95% CI, 77.32%, 86.62%) and 94.13% (95% CI, 90.02%, 96.69%), respectively. The multivariate Cox regression analysis identified a primary site in the mediastinum and alpha fetoprotein (AFP) levels ≥10,000 ng/mL as independent adverse prognostic factors (p < 0.0.0001, χ2 = 23.6638, p = 0.0225, χ2 = 5.2072.). There were no significant differences in OS among children receiving various chemotherapy regimens, such as the BEP, PEB, JEB and other regimens (VBP/VIP and AVCP/IEV) (p < 0.05). Conclusions: The clinical features of GCTs in Chinese pediatrics are similar to those reported in children in Europe and America. The age distribution of pathological types and primary sites in GCTs reflect the developmental origin of type I and type II GCTs transformed from mismigration primordial germ cells (PGCs). Optimizing the current platinum-based chemotherapy regimens and exploring the treatment strategies for MGCTs of the mediastinum are future research directions.
Prediction of Prognosis in Pancreatic Cancer According to Methionyl-tRNA Synthetase 1 Expression as Determined by Immunohistochemical Staining
Authors: Jang Sung Ill , Nahm Ji Hae , Lee See Young , Cho Jae Hee , Do Min-Young , Park Joon Seong , Lee Hye Sun , Yang Juyeon , Kong Jiwon , Jung Seunghwan , Kim Sunghoon , Lee Dong Ki
Published: November 2023

The serum level of CA 19-9 is a prognostic marker for pancreatic ductal adenocarcinoma (PDAC). We evaluated the ability of the expression level of methionyl-tRNA synthetase 1 (MARS1)—which facilitates cancer growth by modulating protein synthesis and the cell cycle—to predict the prognosis of PDAC. Immunohistochemical (IHC) staining was performed on pancreatic specimens obtained from patients with PDAC who were undergoing surgery. High MARS1 expression was defined as equal to, or greater than, that in normal acinar cells. Low MARS1 expression was defined as weaker than in normal acinar cells, and stronger than in the pancreatic duct epithelium. Univariate and multivariate analyses were performed on other factors related to prognosis. Among 137 PDAC patients, no significant differences in baseline characteristics were found between those with high (n = 82) and low (n = 55) MARS1 expression. The median overall survival time of patients with high MARS1 expression was shorter than that of those with low expression (15.2 versus 17.2 months, log-rank test p = 0.044). The median disease-free survival (DFS) was not significantly different between the two groups. However, the DFS was shorter in patients with high than in those with low MARS1 expression (8.9 versus 11.2 months, log-rank test p = 0.067). In a multivariate analysis, lymph node metastasis and high MARS1 expression were associated with a poor prognosis of PDAC. Elevated MARS1 expression detected by IHC staining is associated with a poor prognosis of PDAC, suggesting that MARS1 has potential as a prognostic marker.
A Comparative Analysis of Orthotopic and Subcutaneous Pancreatic Tumour Models: Tumour Microenvironment and Drug Delivery
Authors: Fernandez Jessica Lage , Årbogen Sara , Sadeghinia Mohammad Javad , Haram Margrete , Snipstad Sofie , Torp Sverre Helge , Einen Caroline , Mühlenpfordt Melina , Maardalen Matilde , Vikedal Krister , Davies Catharina de Lange
Published: November 2023

Pancreatic ductal adenocarcinoma (PDAC) remains a challenging malignancy, mainly due to its resistance to chemotherapy and its complex tumour microenvironment characterised by stromal desmoplasia. There is a need for new strategies to improve the delivery of drugs and therapeutic response. Relevant preclinical tumour models are needed to test potential treatments. This paper compared orthotopic and subcutaneous PDAC tumour models and their suitability for drug delivery studies. A novel aspect was the broad range of tumour properties that were studied, including tumour growth, histopathology, functional vasculature, perfusion, immune cell infiltration, biomechanical characteristics, and especially the extensive analysis of the structure and the orientation of the collagen fibres in the two tumour models. The study unveiled new insights into how these factors impact the uptake of a fluorescent model drug, the macromolecule called 800CW. While the orthotopic model offered a more clinically relevant microenvironment, the subcutaneous model offered advantages for drug delivery studies, primarily due to its reproducibility, and it was characterised by a more efficient drug uptake facilitated by its collagen organisation and well-perfused vasculature. The tumour uptake seemed to be influenced mainly by the structural organisation and the alignment of the collagen fibres and perfusion. Recognising the diverse characteristics of these models and their multifaceted impacts on drug delivery is crucial for designing clinically relevant experiments and improving our understanding of pancreatic cancer biology.
Advances and Prospects of d-Tagatose Production Based on a Biocatalytic Isomerization Pathway
Authors: Miao Peiyu , Wang Qiang , Ren Kexin , Zhang Zigang , Xu Tongtong , Xu Meijuan , Zhang Xian , Rao Zhiming
Published: November 2023

d-tagatose is a low-calorie alternative to sucrose natural monosaccharide that is nearly as sweet. As a ketohexose, d-tagatose has disease-relieving and health-promoting properties. Due to its scarcity in nature, d-tagatose is mainly produced through chemical and biological methods. Compared to traditional chemical methods, biological methods use whole cells and isolated enzymes as catalysts under mild reaction conditions with few by-products and no pollution. Nowadays, biological methods have become a very important topic in related fields due to their high efficiency and environmental friendliness. This paper introduces the functions and applications of d-tagatose and systematically reviews its production, especially by l-arabinose isomerase (L-AI), using biological methods. The molecular structures and catalytic mechanisms of L-AIs are also analyzed. In addition, the properties of L-AIs from different microbial sources are summarized. Finally, we overview strategies to improve the efficiency of d-tagatose production by engineering L-AIs and provide prospects for the future bioproduction of d-tagatose.
Modelling 3D Tumour Microenvironment In Vivo: A Tool to Predict Cancer Fate
Authors: Marines Johanna , Lorenzini Francesca , Kissa Karima , Fontenille Laura
Published: November 2023

Recently, many studies demonstrated the fundamental role of the tumour microenvironment (TME) in cancer progression. Here, we describe a method to visualize in 3D the behaviour of tumours in zebrafish embryos. We highlight two major actors of the TME, macrophages and vessels. This valuable tool is transposable to Patient-Derived Xenograft imaging in order to predict the fate of malignant tumours according to the dynamics of their TME.
Characterization of Enlarged Tongues in Cloned Piglets
Authors: Park Mi-Ryung , Ahn Jin Seop , Lee Min Gook , Lee Bo Ram , Ock Sun A , Byun Sung June , Hwang In-Sul
Published: November 2023

Although the efficiency of cloning remains very low, this technique has become the most reliable way to produce transgenic pigs. However, the high rate of abnormal offspring such as an enlarged tongue lowers the cloning efficiency by reducing the early survivability of piglets. Thus, the present study was conducted to identify the characteristics of the enlarged tongue from cloned piglets by histologic and transcriptomic analysis. As a result, it was observed that the tissues from enlarged tongues (n = 3) showed isolated and broken muscle bundles with wide spaces while the tissues from normal tongues (n = 3) showed the tight connection of muscle bundles without space by histological analysis. Additionally, transmission electron microscopy results also showed the formation of isolated and broken muscle bundles in enlarged tongues. The transcriptome analysis showed a total of 197 upregulated and 139 downregulated genes with more than 2-fold changes in enlarged tongues. Moreover, there was clear evidence for the difference between groups in the muscle system process with high relation in the biological process by gene ontology analysis. The analysis of the Kyoto Encyclopedia of Gene and Genomes pathway of differentially expressed genes indicated that the pentose phosphate pathway, glycolysis/gluconeogenesis, and glucagon signaling pathway were also involved. Conclusively, our results could suggest that the abnormal glycolytic regulation may result in the formation of an enlarged tongue. These findings might have the potential to understand the underlying mechanisms, abnormal development, and disease diagnosis in cloned pigs.
PUFGuard: Vehicle-to-Everything Authentication Protocol for Secure Multihop Mobile Communication
Authors: Gebali Fayez , Elhadad Mohamed K.
Published: November 2023

Vehicle area networks (VANs) encompass a spectrum of communication modes, including point-to-point visible light communication, 5G/6G cellular wireless communication, and Wi-Fi ad hoc multihop communication. The main focus of this paper is the introduction and application of physically unclonable functions (PUFs) as a pivotal element in secure key generation, authentication processes, and trust metric definition for neighboring vehicles. The multifaceted protocols proposed herein encompass comprehensive security considerations, ranging from authentication and anonymity to the imperative aspects of the proof of presence, freshness, and ephemeral session key exchanges. This paper provides a systematic and comprehensive framework for enhancing security in VANs, which is of paramount importance in the context of modern smart transportation systems. The contributions of this work are multifarious and can be summarized as follows: (1) Presenting an innovative and robust approach to secure key generation based on PUFs, ensuring the dynamic nature of the authentication. (2) Defining trust metrics reliant on PUFs to ascertain the authenticity and integrity of proximate vehicles. (3) Using the proposed framework to enable seamless transitions between different communication protocols, such as the migration from 5G/6G to Wi-Fi, by introducing the concept of multimodal authentication, which accommodates a wide spectrum of vehicle capabilities. Furthermore, upholding privacy through the encryption and concealment of PUF responses safeguards the identity of vehicles during communication.
Teeth Enamel Ultrastructural Analysis of Selected Equidae Taxa
Authors: Demeshkant Vitalii , Biegalski Michał , Rekovets Leonid
Published: November 2023

This paper presents historical and evolutionary insights into the “tarpan” group of small horses by examining molar tooth enamel ultrastructure. Mathematical methodologies were applied to enhance the analysis. Tooth enamel from species such as Equus gmelini (tarpan), E. latipes, and E. hydruntinus from Pleistocene Ukrainian localities, E. przewalskii from the Chornobyl Exclusion Zone in Ukraine, and E. caballus form sylvaticus (Polish konik) from Roztocze National Park, Poland, underwent scanning microscope examination. Measurements of enamel structures, including prisms (PE) and interprismatic matrix (IPM), were conducted, with the K-index used as their ratio, categorized by enamel type (I, II, III). The findings confirmed that the crystal structures of enamel in these horse groups vary based on genus evolution, diet, and environmental conditions, shaping the enamel’s morphological features. Through analysis, clusters were identified, allowing for potential reconstructions of relationships among study groups. The results revealed distinct differences between species, enabling their classification within an established phenogram. Two primary clusters emerged: one consisting of extinct small horse forms from diverse localities and another grouping modern forms. Notably, the Late Pleistocene European species E. latipes showed close affinities to the latter cluster.