bluuebunny/crossref_metadata_2025 huggingface dataset:
Revolutionizing Cancer Treatment: Recent Advances in Immunotherapy
Authors: Ghemrawi Rose , Abuamer Lama , Kremesh Sedra , Hussien Ghadeer , Ahmed Rahaf , Mousa Walaa , Khoder Ghalia , Khair Mostafa
Published: September 2024

Cancer immunotherapy has emerged as a transformative approach in oncology, utilizing the body’s immune system to specifically target and destroy malignant cells. This review explores the scope and impact of various immunotherapeutic strategies, including monoclonal antibodies, chimeric antigen receptor (CAR)-T cell therapy, checkpoint inhibitors, cytokine therapy, and therapeutic vaccines. Monoclonal antibodies, such as Rituximab and Trastuzumab, have revolutionized treatment paradigms for lymphoma and breast cancer by offering targeted interventions that reduce off-target effects. CAR-T cell therapy presents a potentially curative option for refractory hematologic malignancies, although challenges remain in effectively treating solid tumors. Checkpoint inhibitors have redefined the management of cancers like melanoma and lung cancer; however, managing immune-related adverse events and ensuring durable responses are critical areas of focus. Cytokine therapy continues to play a vital role in modulating the immune response, with advancements in cytokine engineering improving specificity and reducing systemic toxicity. Therapeutic vaccines, particularly mRNA-based vaccines, represent a frontier in personalized cancer treatment, aiming to generate robust, long-lasting immune responses against tumor-specific antigens. Despite these advancements, the field faces significant challenges, including immune resistance, tumor heterogeneity, and the immunosuppressive tumor microenvironment. Future research should address these obstacles through emerging technologies, such as next-generation antibodies, Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-based gene editing, and AI-driven drug discovery. By integrating these novel approaches, cancer immunotherapy holds the promise of offering more durable, less toxic, and highly personalized treatment options, ultimately improving patient outcomes and survival rates.
Dust Pollution in Construction Sites in Point-Pattern Housing Development
Authors: Manzhilevskaya Svetlana
Published: September 2024

Construction in cities and agglomerations is one of the main sources of air pollution in most countries in the world. Fine dust particles, PM0.5–PM10, which form as a result of construction processes, are among the most dangerous pollutants. With the increase in the volume of point-pattern housing development in cities, the task of maintaining clean air and environmental conditions becomes important. This requires research, the monitoring of dust emissions throughout the entire construction period and the development of design solutions based on the results obtained. The study examines the determination of the dispersed composition of dust generated on a construction site. A graphical representation of the dispersed composition is given by constructing integral curves on a logarithmic grid and approximating them using two-link and three-link splines. The gravimetric measurement method was used to analyze the concentration of dust in the air released during construction work near residential areas. Dust analysis at the construction site revealed significant differences in particle size that cannot be explained by statistical errors alone. The reasons for this are both working conditions and climatic factors, including humidity and wind intensity. In this regard, it is preferable to use models that take into account random processes instead of traditional deterministic methods to study the dust that shapes during construction.
Assessment of Vertical Dynamic Responses in a Cracked Bridge under a Pedestrian-Induced Load
Authors: Zhen Bin , Lu Sifan , Ouyang Lijun , Yuan Weixin
Published: September 2024

Cracks, common indicators of deterioration in bridge frameworks, frequently stem from wear and rust, leading to increased local flexibility and changes in the structure’s dynamic behavior. This study examines how these cracks affect the dynamics of footbridges when subjected to loads generated by walking individuals. The pedestrian is modeled as a linear oscillator, while the cracked bridge is represented by a simply supported beam following Euler–Bernoulli’s theory. The use of the Dirac delta function allows for the precise representation of the localized stiffness reduction at the crack location, facilitating the calculation of analytical expressions for the beam’s vibration modes. The research suggests that the presence of cracks minimally affects the bridge’s mid-span displacement. However, with a limited depth of cracks, the appearance of cracks notably amplifies the mid-span acceleration amplitude of the bridge, leading to a pronounced concentration of energy at the third natural frequency of the bridge in the acceleration spectrum. As the depth and number of cracks increase, the acceleration amplitude continues to decrease, but the corresponding spectrum remains almost unchanged. The study’s outcomes enhance the comprehension of how cracks affect the performance of bridge structures when subjected to loads from pedestrians, offering insights for the monitoring and evaluation of the condition of cracked footbridges.
Axial Compression Performance of L-Shaped Partially Encased Steel–Concrete Composite Stub Columns
Authors: Qi Yuansen , Zhu Haochuan , Xu Youwu , Xiao Zhibin , Jin Zhenfen
Published: September 2024

The L-shaped partially encased steel–concrete composite (PEC) stub column, composed of profile steel, concrete, and transverse links, tends to occupy less space than the rectangle-shaped PEC column when used as side or corner columns. In this study, an axial compression test involving three L-shaped PEC stub columns was conducted to investigate the influence of critical factors on axial compression performance. The test results indicated that the axial compression capacity can be effectively enhanced with an increase in material strength. Furthermore, finite element (FE) analysis was carried out with parameters such as material strength, steel thickness, transverse link spacing, transverse link diameter, transverse link distribution, and longitudinal rebar diameter. The results revealed that the primary failure modes of L-shaped PEC columns were concrete spalling and local buckling of the flange. Additionally, it was found that the increase in steel strength, steel thickness, and transverse link diameter, as well as the decrease in transverse link spacing, significantly improved the axial compression capacity and concrete confinement effect. However, an increase in concrete strength diminished the concrete confinement effect. Additionally, the accuracy of the axial compression capacity calculation methods in the Eurocode 4 and T/CECS719-2010 specifications for L-shaped PEC stub columns was verified. Finally, a calculation method based on the superposition principle incorporating the concrete confinement effect was proposed, and validated by comparing with experimental and FE results. Overall, this study could provide a theoretical basis for the engineering application of L-shaped PEC columns.
Exploring the Sustainability-Oriented Strategies of Small- and Medium-Sized Construction Enterprises in China’s Construction Industry under Financing Guarantee Constraints: A Multi-Agent Computational Model Approach
Authors: Mei Zhu , Han Wenbo , Zhang Jingjing , Zhou Qiaomei
Published: September 2024

In the context of China’s swift urbanization and heightened sustainability challenges, SMCEs in the construction industry play a critical role in driving both economic growth and sustainable development. This pioneering study introduces an integrative approach blending sustainability-oriented strategies (SSs) with financing guarantees, addressing key obstacles faced by these firms. Leveraging a multi-agent computational model, we dissect the dynamic interplay among construction SMCEs, governmental bodies, financial institutions, and guarantors, underscoring the transformative impact of financing guarantees on sustainable advancement. Our investigation reveals that optimally structured financing guarantees not only resolve funding challenges but also actively foster adherence to sustainability practices. This dual functionality positions such financial instruments as key enablers of SMCEs’ quest for sustainability, aligning economic objectives with ecological imperatives. Furthermore, we spotlight the transformative effect of strategic management on elevating SMCEs’ commitment to sustainable operations. Collectively, these insights offer actionable pathways for SMCEs embarking on sustainability endeavors, showcasing innovative financial solutions that do not detract from their economic prosperity.
Study on the Characteristics of Community Elderly Care Service Facilities Usage and Optimization Design Based on Life Cycle Theory
Authors: Yang Yujun , Li Chenxi , Zhou Dian
Published: September 2024

As the aging population in China increases, home-based elderly care is set to become the main mode of elderly care in the future. The construction of community elderly care service facilities is receiving more and more attention from society. Currently, residential area design standards in China lack clear guidance on the spatial planning of facilities, which will lead to unreasonable facility layout planning and insufficient convenience in the utilization of facilities by the elderly. Fully considering the distribution characteristics of community elderly care service facilities and the needs of the community life circle when planning residential areas can effectively solve this problem. This study takes Xi’an City as the research object, based on the theory of life circle, through questionnaire surveys and cluster analysis, analyzes the current situation of the construction of elderly care service facilities and the characteristics of the use by the elderly. Combined with the community life circle model, the study scope is divided into community life circle levels, and put forward the planning strategies of coverage rate, number, richness, and spatial layout of the facilities, respectively. These strategies are designed to enhance the quality of life for seniors, ensuring that they have access to essential support and resources within their communities. It demonstrated that middle-aged elderly prefer community canteens and activity centers, while those with limited mobility and multiple chronic diseases have a higher demand for health service centers and community canteens. The utilization weight analysis shows that vegetable markets and supermarkets are most frequently used, whereas health service centers are the least utilized. The research proposes strategic planning enhancements, including full coverage of basic facilities, targeted increases in high-demand facilities, and tailored facilities for elderly characteristics. It recommends cross-community layouts to ensure service radius coverage, development reservations for future needs, and quality improvements to address the low satisfaction rates of existing facilities. The study concludes that a targeted approach to facility planning, considering the elderly’s diverse needs, can enhance the community elderly care service system’s sustainability and effectiveness.
Seismic Behavior of Precast Prestressed Concrete Frame with Hinge-Relocated Mortise–Tenon Connections
Authors: Zhao Hanxi , Takahashi Noriyuki
Published: September 2024

To satisfy the easy-construction demands of precast concrete (PCa) frames after an earthquake, a PCa frame with mortise–tenon (MT) connections is proposed in this paper. MT connections are secured solely through the binding force of unbonded prestressed tendons without grouting for easy construction. The design and construction of the joint are detailed. During an earthquake, the hinge system of the connection allows for slight rotational movements. Finite element analysis was employed to assess the joint’s hysteresis behavior, revealing a three-stage earthquake response mechanism: closing, hinge relocation, and self-centering. Based on the hysteresis performance of the beam and column in the precast prestressed concrete (PCaPC) frame, a seismic response model for PCaPC buildings was established.
The Spatial Patterns and Building Policies of Rural Settlements in the Context of Demolition: The Case of Xian’an, China
Authors: Long Wang , Li Qiang , Feng Zhangxian , Chang Xiaodong , Liao Jiquan
Published: September 2024

In China, the “land-restructuring” policy provides balanced land for urban settlements that is strictly limited in expansion. Therefore, reassessing and adjusting the layout of rural settlements is of great practical significance for promoting rural revitalization. In this paper, taking Xian’an district in Hubei Province as an example, we use the weighted rank-sum ratio comprehensive evaluation method and spatial association analysis method to analyze the development level and spatial pattern of settlements. The results show that: (1) The development level of settlements in Xian’an shows obvious spatial differences, with a spatial pattern of ‘high in the core–low in the periphery’ and ‘high in the northwest–low in the southeast’, which is the result of the combined effect of natural geographical conditions and socioeconomic conditions; (2) The comprehensive development level of settlements, evaluated based on four major indicators—population size, resource endowment, spatial characteristics, and material construction—reveals the presence of cluster effects, distance decay effects, administrative hierarchy effects, and “long board” effects; (3) Within village communities, settlements with significantly high levels and settlements with significantly low levels have a similar geographic distribution and mosaic spatial patterns. Lastly, based on the overall development level and spatial association patterns of settlements, this article presents possible options for governmental settlement governance from the standpoint of rural building management.
A Fuzzy Logic Application to Manage Construction-Cost Escalation
Authors: Canesi Rubina , D’Alpaos Chiara
Published: September 2024

In large-scale projects, such as transport infrastructures, the cost-planning phase stands out as one of the most crucial for the project’s success. Cost and time overruns, during the construction phase, are often the cause of project failure. A meticulous, conscious, and accurate ex-ante analysis of cost and time assessment can greatly contribute to the efficient and effective completion of a project. Various approaches have been developed to estimate and mitigate cost overruns. Such mitigation is subject to careful analysis of project risks, encompassing construction, environmental, social acceptance, and market risks. In this contribution, we propose the implementation of the risk-assessment tool, suggested by the National Anti-Corruption Authority (ANAC), using fuzzy logic to enhance its effectiveness. Thanks to the implementation of fuzzy prioritizations, the risk matrix and the associated risk levels, which are obtained by combining the event’s probability of occurrence and its expected impact on costs, have been clearly and structurally defined. This tool can facilitate risk ranking and, therefore, the implementation of their management strategies during the design and construction phases as well as the consensus-creation process. This application can therefore be used by public authorities as a transparent and manageable tool to assess expected risk during the design and implementation phases of the project.
Exploring Inclusion, Diversity, Equity, and Accessibility in the Built Environment: A Case Study
Authors: Zallio Matteo , Chivǎran Camelia , Clarkson P. John
Published: September 2024

Continuous changes in society and the need for sustainable development demand updates in designing better built environments to respond to the variety of user needs. Notwithstanding the growing interest of research and the introduction of guidelines and standards on inclusion, diversity, equity, and accessibility, there are still several limitations in effectively and efficiently embedding such principles for the design of buildings and neighborhoods. Previous research demonstrated the critical need for innovative tools and methods to support professionals in designing responsive, inclusive spaces for an extended range of users. This article reports the results of a pilot study using the new IDEA Audit Tool for assessing how inclusion, diversity, equity, and accessibility are perceived by building occupants in a specific facility. The analysis of significant data provided by this study shows the challenges and highlights the benefits of the tool, including fostering an evidence-based decision-making process, speeding up the prioritization of critical design improvements, demonstrated through a six-month trial with a London-based inclusive design firm. The research-driven outcomes showcase the huge potential that the tool offers to improve the company strategy while evolving towards more inclusive, accessible spaces that foster diversity and equity, and has the potential to be replicated in several fields of action to raise awareness and improve the application of IDEA principles in all phases of the design process.
Three-Dimensional Web-Based Client Presentation of Integrated BIM and GIS for Smart Cities
Authors: Varlık Abdullah , Dursun İsmail
Published: September 2024

Smart cities use technological solutions to reduce the drawbacks of urban living. The importance of BIM and GIS integration has increased with the popularity of smart city and 3D city concepts in recent years. In addition to 3D city models, Building Information Modeling (BIM) is an essential element of smart cities. The 3D city model web client in this study displays three-dimensional (3D) city models created using photogrammetric techniques, BIM, and campus infrastructure projects. The comparison and integration of the aforementioned systems were evaluated. A web-based 3D client framework and implementation for combined BIM and 3D city models are the goals of the submitted work. The Web is a very challenging platform for 3D data presentation. The Cesium engine based on HTML5 and WebGL is an open-source creation and the virtualcityMAP application using the Cesium infrastructure was used in this study.
Advanced Risk Assessment for Deep Excavation in Karst Regions Using Improved Dempster–Shafer and Dynamic Bayesian Networks
Authors: Lei Zhenyu , Wang Yanhong , Zhang Yu , Gu Feng , Zan Zihui , Mei Yuan , Liu Wenzhan , Zhou Dongbo
Published: September 2024

This study presents a novel risk-assessment methodology for deep foundation pit projects in karst regions, aimed at enhancing project safety and decision-making processes. This approach amalgamates fuzzy dynamic Bayesian networks with a refined Dempster–Shafer (DS) evidence theory to tackle the intricate uncertainties present in such contexts. A comprehensive risk index system, derived from historical accident cases, relevant standards, and the literature, encompasses environmental, design, construction, and management factors. Initial probabilities for each risk factor are determined through the integration of expert knowledge and fuzzy theory. The enhanced Dempster–Shafer theory is utilized to fuse diverse information sources, culminating in a robust and dynamic risk evaluation model. This model leverages real-time monitoring data to dynamically assess and adjust risk levels throughout the construction process. The validation of the proposed method is demonstrated through a detailed case study of the Guangzhou Tangxi Section 1 deep foundation pit project, which effectively identified critical risk factors and facilitated proactive construction strategy adjustments. To further evaluate the reliability of the methodology, comparisons were made with three alternative methods, and applications were conducted on three additional deep foundation pit projects. These comparative analyses confirm the superior reliability and applicability of the proposed methodology across varied scenarios.
Experimental Study of the Influence of Supplementary Reinforcement on Tensile Breakout Capacity of Headed Anchors in Nuclear Power Plant Equipment Foundations
Authors: Xu Yang , Chen Chaoqun , Xie Minglei , Gong Jinxin
Published: September 2024

Anchor bolts are often used in nuclear power plants to connect equipment and equipment foundations. Under a severe earthquake, tensile breakout failure is prone to occur in the anchor bolts. As the total amount of installed machines rises, the inertial forces transferred to the anchor bolts under seismic loads also increase significantly. Therefore, the capacity is no longer satisfied by concrete alone, and specialized supplementary reinforcement needs to be installed around the bolts. The study analyzed the tensile behavior of anchor bolts in foundations with supplementary reinforcement experimentally. A total of 16 single-headed anchors in RC foundations with various diameters, yield strengths, and forms of supplementary reinforcement were tested under monotonic tensile loading. The results show that supplemental tie bars and supplemental U-shaped bars, respectively, rely on the bond with the concrete and their own tensile strength to increase the tensile breakout capacity. Furthermore, based on the failure mechanism, a new model considering the terms of concrete resistance and reinforcement resistance for the tensile breakout capacity of headed anchors around with supplementary reinforcement was proposed. Compared with the strut–tie model by EN 1992-4:2018, the predicted results of the model proposed by this study are relatively consistent with the experimental results, while the results by EN 1992-4:2018 are overly conservative.
Shear Force of Interior Beam–Column Joints under Symmetrical Loading with Two Transverse Forces on the Beam
Authors: Doicheva Albena
Published: September 2024

The beam-to-column connection is a particularly vulnerable element in frame structures under seismic action and is often responsible for building damages. Experimental investigations carried out over the past six decades on shear strength in frame joints have not led to the establishment of a uniform procedure in the design codes of different countries. The reason lies probably in the varied nature of the investigated parameters and in the varied configurations of beam–column connections. A good knowledge of the forces passing through the frame joints in the beam–beam and column–column direction would allow both their adequate computation in new buildings and the verification of existing ones without requiring experimental studies. In the design codes of the leading countries in seismic engineering, the shear force is determined by the capacitive method, considering only the area of the longitudinal reinforcement of the beam passing through the column. This method shows us how much shear force the beam reinforcement can take, but not what the magnitude of the resulting forces actually is as a result of the acting loads. In addition, the method of the codes does not indicate the contribution of the concrete to the total magnitude of the shear force in the beam–column connection. In the proposed mathematical model for calculating the forces that leave the beam, the full dimensions of the cross-section of the beam were taken into account. The material properties and cross-sectional shape were also taken into account. A determining factor for the magnitude of forces entering the beam–column joint is the acting load on the beam. In this paper, the load of two transverse forces was considered. The forces are applied in different possible positions, while remaining symmetrically located on the beam. The calculations are based on Menabrea’s theorem to determine the hyperstatic unknowns. The results of the proposed method for the considered beam show that the magnitude of the shear force differs from that accepted in the literature and the norms by 2% to 27%, depending on the stage of development of the crack. In comparison, the Eurocode-recommended method shows differences in the order of 27% to 40% for the adopted beam under static loads.
Immunological Tumor Microenvironment of Solitary Fibrous Tumors—Associating Immune Infiltrate with Variables of Prognostic Significance
Authors: Medina-Ceballos Emilio , Machado Isidro , Giner Francisco , Blázquez-Bujeda Álvaro , Espino Mónica , Navarro Samuel , Llombart-Bosch Antonio
Published: September 2024

Background and objectives: Solitary fibrous tumors (SFTs) are morphologically heterogeneous tumors characterized by the NAB2::STAT6 gene fusion. Clinical outcomes may vary widely, and while most cases have favorable outcomes, some can progress to aggressive disease, manifesting as recurrence and metastasis, and ultimately resulting in patient death. Herein, we analyze the immunological tumor microenvironment (ITME) of SFTs, aiming to determine its prognostic value and correlation with established risk stratification systems (RSSs). Methods: A retrospective observational multicenter study of 52 fusion-confirmed SFTs with clinical follow-up data. Immunohistochemical analysis including CD163, CD68, CD3, CD8, CD20, PDL-1, PD-1, and LAG1 were evaluated in tissue microarrays, using an analog scale with scores ranging from 0 to 3 (0 = ≤9, 1 = 10–49, 2 = 50–99, and 3 = >100 positive cells per 10 high-power fields). The expression of these markers was correlated with clinical outcomes, morphological characteristics previously evaluated in whole slide tissue sections (hypercellularity/hypocellularity, round–oval or spindle dominant constituent cell (DCC) morphology, and necrosis), Ki67, overall survival, and RSS. Results: Only one of the fifty-two cases studied showed progression. In the multivariate analysis, neither the presence nor absence of immune cells (B-lymphocytes, T-lymphocytes, and macrophages) showed any association with the assessed RSSs (Demicco, Sugita, G-score, and Huang). Interestingly, the case that showed progression had high immune infiltrate with expression of CD68, CD163, CD8, and CD20 markers (score of 3). Round–oval cell morphology was associated with the presence of higher levels of CD163 macrophages. Lastly, the scant presence of CD20+ lymphocytes correlated with less necrosis, and cases with higher PDL-1 expression correlated with increased Ki67 values. All cases were negative for LAG-1 and PD-1. Conclusions: SFT ITME components correlated with independent variables with prognostic significance. Nevertheless, ITME did not correlate with RSS scores.
Adverse Obstetric Outcomes after Breast Cancer Diagnosis: An Observational Database Study in Germany
Authors: Scholz Anna Sophie , von Au Alexandra , Gutsfeld Raphael , Dijkstra Tjeerd Maarten Hein , Dannehl Dominik , Hassdenteufel Kathrin , Hahn Markus , Hawighorst-Knapstein Sabine , Chaudhuri Ariane , Bauer Armin , Wallwiener Markus , Brucker Sara Yvonne , Hartkopf Andreas Daniel , Wallwiener Stephanie
Published: September 2024

Background/Objectives: Breast cancer may negatively affect later pregnancy and childbirth. We aimed to analyze the impact of previous breast cancer on obstetric outcomes in postdiagnosis pregnancies. Methods: Insurance claims data in Southern Germany were used to identify breast cancer (BC) survivors with at least one subsequent delivery after cancer diagnosis between 2010 and 2020. In total, 74 BC survivors were compared to 222 age-matched controls with frequency matching on their age at their postdiagnosis delivery. Results: Endocrine therapy was associated with a significantly lower probability of birth compared to BC survivors without endocrine therapy (HR 0.36; 95% CI 0.18–0.53; p < 0.0001). The risks of preterm birth, low birth weight (LBW), gestational diabetes, hypertensive disorders, and cesarean section were not significantly increased among BC survivors compared to healthy controls. BC survivors were at an increased risk for a small-for-gestational-age (SGA) fetus (OR 3.24; 95% CI 1.17–8.97, p = 0.03). Delivery in less than 2 years after diagnosis increased the risk for SGA (OR 5.73; 95% CI 1.37–24.02, p = 0.03) and LBW (OR 4.57; 95% CI 1.32–15.87, p = 0.02). Conclusions: Our findings are encouraging regarding the risks of preterm delivery, gestational diabetes, hypertensive disorders, and cesarean section to women who consider pregnancy after BC. Delivery in less than 2 years after diagnosis was associated with an increased risk for SGA and LBW.
Advancing Cholangiocarcinoma Care: Insights and Innovations in T Cell Therapy
Authors: Dadgar Neda , Arunachalam Arun K. , Hong Hanna , Phoon Yee Peng , Arpi-Palacios Jorge E. , Uysal Melis , Wehrle Chase J. , Aucejo Federico , Ma Wen Wee , Melenhorst Jan Joseph
Published: September 2024

Cholangiocarcinoma (CCA) is a rare and aggressive malignancy originating from the bile ducts, with poor prognosis and limited treatment options. Traditional therapies, such as surgery, chemotherapy, and radiation, have shown limited efficacy, especially in advanced cases. Recent advancements in immunotherapy, particularly T cell-based therapies like chimeric antigen receptor T (CAR T) cells, tumor-infiltrating lymphocytes (TILs), and T cell receptor (TCR)-based therapies, have opened new avenues for improving outcomes in CCA. This review provides a comprehensive overview of the current state of T cell therapies for CCA, focusing on CAR T cell therapy. It highlights key challenges, including the complex tumor microenvironment and immune evasion mechanisms, and the progress made in preclinical and clinical trials. The review also discusses ongoing clinical trials targeting specific CCA antigens, such as MUC1, EGFR, and CD133, and the evolving role of precision immunotherapy in enhancing treatment outcomes. Despite significant progress, further research is needed to optimize these therapies for solid tumors like CCA. By summarizing the most recent clinical results and future directions, this review underscores the promising potential of T cell therapies in revolutionizing CCA treatment.
Tolerability and Outcomes for Treatment of Older Myxoid Liposarcoma Population
Authors: Coombs Reilly A. , Jebastin Thangaiah Judith , Siontis Brittany L. , Robinson Steven I. , Okuno Scott H. , Houdek Matthew T. , Xu-Welliver Meng , Ho Thanh P.
Published: September 2024

Background: Myxoid liposarcoma predominantly affects young and middle-aged individuals, and little is known regarding treatment tolerability and outcomes in older patients. This study aims to better understand this older patient population. Methods: This single institution retrospective study included patients aged 70 years and older with localized (non-metastatic) myxoid liposarcoma. Results: Sixteen patients were included. The median age was 75 years, and 9 (56%) were female. Fourteen (88%) were extremity tumors and two (12%) were trunk. The median tumor size was 10.4 cm (range, 3.6 to 28 cm). Five (31%) tumors had a round cell component. All patients had surgery. Fourteen (88%) had perioperative radiation, and three (19%) had perioperative chemotherapy. One patient had postoperative infection, and one patient had neutropenic fever from preoperative chemotherapy. The median follow up from surgery was 6.3 years. Eight (50%) patients died from MLPS. The median relapse-free survival and overall survival were 34 months and 75 months, respectively. Conclusions: Most older patients with localized MLPS received perioperative radiation therapy with surgery, and few serious toxicities were reported. Even with treatment, half of the patients relapsed.
The Contribution of Macrophage Plasticity to Inflammatory Arthritis and Their Potential as Therapeutic Targets
Authors: Kulakova Karina , Lawal Tope Remilekun , Mccarthy Eoghan , Floudas Achilleas
Published: September 2024

Inflammatory arthritis are common chronic inflammatory autoimmune diseases characterised by progressive, destructive inflammation of the joints leading to a loss of function and significant comorbidities; importantly, there are no cures and only 20% of patients achieve drug-free remission for over 2 years. Macrophages play a vital role in maintaining homeostasis, however, under the wrong environmental cues, become drivers of chronic synovial inflammation. Based on the current “dogma”, M1 macrophages secrete pro-inflammatory cytokines and chemokines, promoting tissue degradation and joint and bone erosion which over time lead to accelerated disease progression. On the other hand, M2 macrophages secrete anti-inflammatory mediators associated with wound healing, tissue remodelling and the resolution of inflammation. Currently, four subtypes of M2 macrophages have been identified, namely M2a, M2b, M2c and M2d. However, more subtypes may exist due to macrophage plasticity and the ability for repolarisation. Macrophages are highly plastic, and polarisation exists as a continuum with diverse intermediate phenotypes. This plasticity is achieved by a highly amenable epigenome in response to environmental stimuli and shifts in metabolism. Initiating treatment during the early stages of disease is important for improved prognosis and patient outcomes. Currently, no treatment targeting macrophages specifically is available. Such therapeutics are being investigated in ongoing clinical trials. The repolarisation of pro-inflammatory macrophages towards the anti-inflammatory phenotype has been proposed as an effective approach in targeting the M1/M2 imbalance, and in turn is a potential therapeutic strategy for IA diseases. Therefore, elucidating the mechanisms that govern macrophage plasticity is fundamental for the success of novel macrophage targeting therapeutics.
Microgravity Effect on Pancreatic Islets
Authors: Zeger Lukas , Barasa Povilas , Han Yilin , Hellgren Josefin , Redwan Itedale Namro , Reiche Myrthe E. , Florin Gunnar , Christoffersson Gustaf , Kozlova Elena N.
Published: September 2024

We previously demonstrated that boundary cap neural crest stem cells (BCs) induce the proliferation of beta-cells in vitro, increase survival of pancreatic islets (PIs) in vivo after transplantation, and themselves strongly increase their proliferation capacity after exposure to space conditions. Therefore, we asked if space conditions can induce the proliferation of beta-cells when PIs are alone or together with BCs in free-floating or 3D-printed form. During the MASER 15 sounding rocket experiment, half of the cells were exposed to 6 min of microgravity (µg), whereas another group of cells were kept in 1 g conditions in a centrifuge onboard. The proliferation marker EdU was added to the cells just before the rocket reached µg conditions. The morphological assessment revealed that PIs successfully survived and strongly proliferated, particularly in the free-floating condition, though the fusion of PIs hampered statistical analysis. Proliferation of beta-cells was displayed in 3D-printed islets two weeks after µg exposure, suggesting that the effects of µg may be delayed. Thus, PIs in 3D-printed scaffolds did not fuse, and this preparation is more suitable than free-floating specimens for morphological analysis in µg studies. PIs maintained their increased proliferation capacity for weeks after µg exposure, an effect that may not appear directly, but can emerge after a delay.
COL6A6 Peptide Vaccine Alleviates Atherosclerosis through Inducing Immune Response and Regulating Lipid Metabolism in Apoe−/− Mice
Authors: Tang Dongmei , Liu Yan , Duan Rui , Lin Run , Li Zhonghao , Liu Xianyan , Huang Jingrong , Zhao Ming
Published: September 2024

Atherosclerosis is an autoimmune disease characterized by lipid imbalances and chronic inflammation within blood vessels, with limited preventive and treatment options currently available. In this study, a vaccine prepared with COL6A6 peptide (named the Pep_A6 vaccine) was administered to immunize Apoe−/− mice, and the immune mechanism of the Pep_A6 vaccine against atherosclerosis was first investigated. The results of arterial oil red O staining demonstrated that the Pep_A6 vaccine significantly reduced the atherosclerotic plaque area in Apoe−/− mice fed with a high-fat diet for 20 weeks. A flow cytometry analysis revealed that the Pep_A6 vaccine inhibited Th1 cell differentiation and increased the proportion of Treg cells. Furthermore, there was a significant increase in Ly6Clow monocytes observed in the vaccinated group. The ELISA results showed that the Pep_A6 vaccine induced a significant expression of Pep_A6-specific antibody IgG and IgG1 in mouse serum. Additionally, we found that the Pep_A6 vaccine significantly decreased serum LDL-C content and regulated the expression of genes related to liver lipid metabolism. Together, our findings suggest that the Pep_A6 vaccine alleviates atherosclerosis by inducing a positive immune response and regulating lipid metabolism, providing new insights into potential prevention strategies for atherosclerosis as an innovative vaccine.
The Nucleolus and Its Interactions with Viral Proteins Required for Successful Infection
Authors: Ulloa-Aguilar José Manuel , Herrera Moro Huitron Luis , Benítez-Zeferino Rocío Yazmin , Cerna-Cortes Jorge Francisco , García-Cordero Julio , León-Reyes Guadalupe , Guzman-Bautista Edgar Rodrigo , Farfan-Morales Carlos Noe , Reyes-Ruiz José Manuel , Miranda-Labra Roxana U. , De Jesús-González Luis Adrián , León-Juárez Moises
Published: September 2024

Nuclear bodies are structures in eukaryotic cells that lack a plasma membrane and are considered protein condensates, DNA, or RNA molecules. Known nuclear bodies include the nucleolus, Cajal bodies, and promyelocytic leukemia nuclear bodies. These bodies are involved in the concentration, exclusion, sequestration, assembly, modification, and recycling of specific components involved in the regulation of ribosome biogenesis, RNA transcription, and RNA processing. Additionally, nuclear bodies have been shown to participate in cellular processes such as the regulation of transcription of the cell cycle, mitosis, apoptosis, and the cellular stress response. The dynamics and functions of these bodies depend on the state of the cell. It is now known that both DNA and RNA viruses can direct their proteins to nuclear bodies, causing alterations in their composition, dynamics, and functions. Although many of these mechanisms are still under investigation, it is well known that the interaction between viral and nuclear body proteins is necessary for the success of the viral infection cycle. In this review, we concisely describe the interaction between viral and nuclear body proteins. Furthermore, we focus on the role of the nucleolus in RNA virus infections. Finally, we discuss the possible implications of the interaction of viral proteins on cellular transcription and the formation/degradation of non-coding RNAs.
Screening a Compound Library to Identify Additives That Boost Cytochrome P450 Enzyme Function in Vascularised Liver Spheres
Authors: Lucendo-Villarin Baltasar , Wang Yu , Mallanna Sunil K. , Kimbrel Erin A. , Hay David C.
Published: September 2024

To accurately study human organ function and disease ‘in the dish’, it is necessary to develop reliable cell-based models that closely track human physiology. Our interest lay with the liver, which is the largest solid organ in the body. The liver is a multifunctional and highly regenerative organ; however, severe liver damage can have dire consequences for human health. A common cause of liver damage is adverse reactions to prescription drugs. Therefore, the development of predictive liver models that capture human drug metabolism patterns is required to optimise the drug development process. In our study, we aimed to identify compounds that could improve the metabolic function of stem cell-derived liver tissue. Therefore, we screened a compound library to identify additives that improved the maturity of in vitro-engineered human tissue, with the rationale that by taking such an approach, we would be able to fine-tune neonatal and adult cytochrome P450 metabolic function in stem cell-derived liver tissue.
Voltammetric Sensor Based on Titania Nanoparticles Synthesized with Aloe vera Extract for the Quantification of Dithiophosphates in Industrial and Environmental Samples
Authors: Vilasó-Cadre Javier E. , Ramírez-Rodríguez Alondra , Hidalgo Juan , Reyes-Domínguez Iván A. , Cruz Roel , Flores Mizraim U. , Rodríguez-Torres Israel , Briones-Gallardo Roberto , Hidalgo Luis , Piña Leyte-Vidal Juan Jesús
Published: September 2024

In this work, TiO2 spherical nanoparticles with a mean diameter of 10.08 nm (SD = 4.54 nm) were synthesized using Aloe vera extract. Rutile, brookite, and anatase crystalline phases were identified. The surface morphology of a carbon paste electrode does not change in the presence of nanoparticles; however, the surface chemical composition does. The voltammetric response to dicresyl dithiophosphate was higher when the electrode was modified with TiO2 nanoparticles. After an electrochemical response study from pH 1.0 to 12.0, pH 7.0 was selected for the electroanalysis. The electroactive area of the modified sensor was 0.036 cm2, while it was 0.026 cm2 for the bare electrode. The oxidation process showed mixed adsorption-diffusion control. The charge transfer resistance of the modified sensor (530.1 Ω, SD = 4.08 Ω) was much lower than that of the bare electrode (4298 Ω, SD = 8.53 Ω). The linear quantitative range by square wave voltammetry was from 5 to 150 μmol/L, with a limit of detection of 1.89 μmol/L and a limit of quantification of 6.26 μmol/L under optimal pulse parameters of 50 Hz frequency, 1 mV step potential, and 25 mV pulse amplitude. The sensor response was repeatable and reproducible over 30 days. The results on real flotation and synthetically contaminated soil samples were statistically equivalent to those obtained by UV-vis spectrophotometry. A dithiocarbamate showed an interfering effect on the sensor response to dithiophosphate.
Are There Benefits to Breastfeeding for Long Durations That Continue after Breastfeeding Has Stopped? An Analysis of Acute Respiratory Illness in Nigerian Children
Authors: Ademu Lilian Ouja , Paul Rajib , Racine Elizabeth F.
Published: September 2024

Background: While an abundance of evidence exists regarding infectious outcomes in children as they relate to the short-term benefits of breastfeeding, there is limited evidence related to similar impacts beyond one year and after breastfeeding has stopped. Specifically, little is known about the long-term benefits of breastfeeding for acute health outcomes after infancy, particularly in Nigeria. Methods: The Nigeria Demographic and Health Survey data was used in this study. We utilized data (n = 5391) on children who had stopped breastfeeding for at least 12 months before the survey. Breastfeeding duration was categorized into 1–6 months, 7–12 months, 13–18 months, 18–24 months, and > 24 months. Any recent incident of acute respiratory illness in children was operationalized using the responses to related questions (recent incidents of fever, cough, running nose, and short, rapid, or difficulty breathing in children). Adjusted logistic regression was used to estimate odds ratios, and statistical significance was determined at p ≤ 0.05. Results: Post-infancy and after breastfeeding had stopped, the odds of recent acute respiratory illness were significantly less (AOR = 0.37, 95% CI [0.15–0.79], p = 0.04) in children breastfed for 19–24 months compared to those breastfed for 1–6 months. No significant association was found between the other durations and ARI post-infancy (p > 0.05). Conclusions: These findings indicate that breastfeeding for up to 24 months has a long-term protective effect from an acute health condition that contributes to the high under-five mortality rates recorded for decades in Nigeria specifically, and more broadly, in sub-Saharan Africa.
BMI, Dental Caries, and Risk Factors among Elementary School Children: A Cross-Sectional Study
Authors: Farsi Deema J.
Published: September 2024

Background/Objectives: Obesity and dental caries are multifactorial diseases with high prevalence amongst Saudi children. The aim of the study was to determine their association with common risk factors. Methods: This cross-sectional study examined 300 children attending elementary schools. After taking their height and weight, their body mass indices (BMIs) were calculated. Oral examination was performed to record the decayed, missed, and filled scores (dmft/DMFT). A thorough questionnaire was compiled and validated to gather information on diet and physical activity (PA). The KIDMED score was calculated from a 16-item questionnaire to assess diet. Junk food and PA scores were also calculated based on relevant questions. Nonparametric tests were used to assess the associations between the scores and health outcomes (dmft/DMFT and BMI). Results: Fifty-eight of the children had poor diets, which was associated with higher dmft/DMFT (p = 0.012). PA levels were very low, and the average PA score was 2.12 ± 0.61. No association was found between BMI percentiles and PA level, nor between BMI percentiles and diet quality. Older children had lower BMI percentiles compared with younger children (coefficient = −9.35, 95% CI: −17.05, −1.65), and a borderline significant negative association was observed between dmft/DMFT and BMI percentile. Conclusions: Poor diets and chips consumption were related to dental caries. Obesity was not related to diet quality nor PA level.
Single Center-Based Real-World Experience on Anti-IL 1 Biological Response Modifiers: A Case Series and Literature Review
Authors: Jones Olcay
Published: September 2024

Background: This communication summarizes our single-center experience with the use of anti-IL-1 biologic response modifiers for treating autoimmune and autoinflammatory conditions in children. Methods: We outline our rationale for the off-label use of anakinra and discuss emerging treatment paradigms that necessitate further research and validation. Results: Anakinra has enabled personalized treatment, whether used as a single agent on an as-needed basis, as part of a background treatment regimen, or in combination with colchicine. Our data also highlight the significance of anakinra in treating post-infectious inflammatory diseases, demonstrating its high efficacy in novel applications such as rheumatic fever and post-viral arthritis. Canakinumab, on the other hand, has provided long-term remission. Both medications were well-tolerated, with no serious adverse effects reported. Conclusions: Based on our observations and successful outcomes, we advocate for future collaborative efforts to improve access to anti-IL-1 medications to better manage excessive and harmful inflammation in children.
Food Insecurity Screening and Referral Practices of Pediatric Clinicians in Metropolitan Washington, DC
Authors: Essel Kofi , Burke Michael , Fischer Laura , Weissman Mark , Dietz William
Published: September 2024

Background/Objectives: In 2022, 17.3% of US households with children experienced food insecurity (FI). The objective of this study was to examine pediatric clinicians’ FI screening and management immediately following the release of the American Academy of Pediatrics (AAP) 2015 FI Policy Statement. Methods: Data were collected in 2016 from 85 primary care pediatric clinicians via an online survey of clinicians in the Washington, DC metropolitan area. Descriptive statistics were calculated using univariate/bivariate analyses. Fisher’s exact test and Chi-square tests were used to explore the association between FI screening, health insurance, and clinician demographics. Results: Sixty-six percent of clinicians indicated that they infrequently screened for FI. Only 13% of clinicians used a standardized FI screening tool. Forty-five percent of clinicians screened for FI only when they perceived an acute concern. About 70% of them screened for FI when a patient presented with poor weight gain or was underweight. Conclusions: Immediately after the release of the AAP Policy Statement, it was found that few pediatric clinicians appropriately and frequently screened for FI in our regional sample. Our data emphasize the common misconceptions held by clinicians around FI and the necessity to incorporate training that underscores the invisibility of FI along with effective techniques to screen and intervene.