bluuebunny/crossref_metadata_2025 huggingface dataset:
The Sobering Sting: Oleoyl Serotonin Is a Novel Stephanoconus Snail Venom-Derived Antagonist of Cannabinoid Receptors That Counteracts Learning and Memory Deficits
Authors: An Dongchen , Carrazoni Guilherme Salgado , Souto das Neves Ben-Hur , D’Hooge Rudi , Peigneur Steve , Tytgat Jan
Published: February 2024

Cannabinoid receptors (CB1 and CB2) are promising targets for a better understanding of neurological diseases. Nevertheless, only a few ligands of CB have reached clinical application so far. Venoms are considered as interesting sources of novel biologically active compounds. Here, we describe an endocannabinoid-like molecule, oleoyl serotonin (OS), present in the venom of Stephanoconus snails. Using electrophysiological assays, it was shown that OS inhibits CB1 and CB2. Structure–activity relationship studies using a chimeric CB1/2 revealed that the domain encompassing the transmembrane helix V (TMHV)– intracellular loop 3 (ICL3)–TMHVI of the CB2 is critical for the binding and function of OS. We concluded that OS binds to sites of the CB2 that are different from the binding sites of the non-selective CB agonist WIN55,212-2. Behavioral assays in mice showed that OS counteracted learning and memory deficits caused by WIN55,212-2. Furthermore, a selectivity screening of OS showed high selectivity for CB over various ion channels and receptors. Overall, OS may represent a new approach to the prevention and treatment of learning and memory cognition impairment in neurological diseases.
L-DOS47 Elevates Pancreatic Cancer Tumor pH and Enhances Response to Immunotherapy
Authors: Jardim-Perassi Bruna Victorasso , Irrera Pietro , Oluwatola Oluwaseyi E. , Abrahams Dominique , Estrella Veronica C. , Ordway Bryce , Byrne Samantha R. , Ojeda Andrew A. , Whelan Christopher J. , Kim Jongphil , Beatty Matthew S. , Damgaci-Erturk Sultan , Longo Dario Livio , Gaspar Kim J. , Siegers Gabrielle M. , Centeno Barbara A. , Lau Justin Y. C. , Pilon-Thomas Shari A. , Ibrahim-Hashim Arig , Gillies Robert J.
Published: February 2024

Acidosis is an important immunosuppressive mechanism that leads to tumor growth. Therefore, we investigated the neutralization of tumor acidity to improve immunotherapy response. L-DOS47, a new targeted urease immunoconjugate designed to neutralize tumor acidity, has been well tolerated in phase I/IIa trials. L-DOS47 binds to CEACAM6, a cell-surface protein that is highly expressed in gastrointestinal cancers, allowing urease to cleave endogenous urea into two NH4+ and one CO2, thereby raising local pH. To test the synergetic effect of neutralizing tumor acidity with immunotherapy, we developed a pancreatic orthotopic murine tumor model (KPC961) expressing human CEACAM6. Using chemical exchange saturation transfer–magnetic resonance imaging (CEST-MRI) to measure the tumor extracellular pH (pHe), we confirmed that L-DOS47 raises the tumor pHe from 4 h to 96 h post injection in acidic tumors (average increase of 0.13 units). Additional studies showed that combining L-DOS47 with anti-PD1 significantly increases the efficacy of the anti-PD1 monotherapy, reducing tumor growth for up to 4 weeks.
Treated and Untreated Primary Progressive Multiple Sclerosis: Walkthrough Immunological Changes of Monocytes and T Regulatory Cells
Authors: Ipavec Nina , Rogić Vidaković Maja , Markotić Anita , Pavelin Sanda , Buljubašić Šoda Maja , Šoda Joško , Dolić Krešimir , Režić Mužinić Nikolina
Published: February 2024

The objective of this study was to investigate regulatory T cells (Tregs) and monocytes; specifically, the expression of CTLA-4 (CD152) and FOXP3+ in CD4+CD25+ Tregs and the expression of CD40+ and CD192+ monocyte subpopulations in subjects with primary progressive multiple sclerosis (PPMS). Immunological analysis was conducted on peripheral blood samples collected from the 28 PPMS subjects (15 treated with ocrelizumab and 13 untreated PPMS subjects) and 10 healthy control subjects (HCs). The blood samples were incubated with antihuman CD14, CD16, CD40, and CD192 antibodies for monocytes and antihuman CD4, CD25, FOXP3, and CTLA-4 antibodies for lymphocytes. The study results showed that in comparison to HCs both ocrelizumab treated (N = 15) and untreated (N = 13) PPMS subjects had significantly increased percentages of CTLA-4+ and FOXP3+ in CD4+CD25+ Tregs. Further, ocrelizumab treated PPMS subjects, compared to the untreated ones, had significantly decreased percentages of CD192+ and CD40+ nonclassical monocytes. Increased percentages of CTLA-4+ and FOXP3+ in CD4+CD25+ Tregs in both ocrelizumab treated and untreated PPMS subjects indicates the suppressive (inhibitory) role of Tregs in abnormal immune responses in PPMS subjects. Decreased percentages of CD40+ and CD192+ non-classical CD14+CD16++ monocytes for treated compared to untreated PPMS subjects suggest a possible role for ocrelizumab in dampening CNS inflammation.
Activation of MAP Kinase Pathway by Polyisoprenylated Cysteinyl Amide Inhibitors Causes Apoptosis and Disrupts Breast Cancer Cell Invasion
Authors: Lazarte Jassy Mary S. , Lamango Nazarius S.
Published: February 2024

Prognoses for TNBC remain poor due to its aggressive nature and the lack of therapies that target its “drivers”. RASA1, a RAS-GAP or GTPase-activating protein whose activity inhibits RAS signaling, is downregulated in up to 77% of TNBC cases. As such, RAS proteins become hyperactive and similar in effect to mutant hyperactive RAS proteins with impaired GTPase activities. PCAIs are a novel class of agents designed to target and disrupt the activities of KRAS and other G-proteins that are hyperactive in various cancers. This study shows the anticancer mechanisms of the PCAIs in two breast cancer cell lines, MDA-MB-468 and MDA-MB-231. PCAIs (NSL-YHJ-2-27) treatment increased BRAF phosphorylation, whereas CRAF phosphorylation significantly decreased in both cell lines. Moreover, the PCAIs also stimulated the phosphorylation of MEK, ERK, and p90RSK by 116, 340, and 240% in MDA-MB-468 cells, respectively. However, in MDA-MB-231 cells, a significant increase of 105% was observed only in p90RSK phosphorylation. Opposing effects were observed for AKT phosphorylation, whereby an increase was detected in MDA-MB-468 cells and a decrease in MDA-MB-231 cells. The PCAIs also induced apoptosis, as observed in the increased pro-apoptotic protein BAK1, by 51%, after treatment. The proportion of live cells in PCAIs-treated spheroids decreased by 42 and 34% in MDA-MB-468 and MDA-MB-231 cells, respectively, which further explains the PCAIs-induced apoptosis. The movement of the cells through the Matrigel was also inhibited by 74% after PCAIs exposure, which could have been due to the depleted levels of F-actin and vinculin punctate, resulting in the shrinkage of the cells by 76%, thereby impeding cell movement. These results show promise for PCAIs as potential therapies for TNBC as they significantly inhibit the hallmark processes and pathways that promote cell proliferation, migration, and invasion, which result in poor prognoses for breast cancer patients.
Bidirectional and Stepwise Rotation of Cells and Particles Using Induced Charge Electroosmosis Vortexes
Authors: Wang Shaoxi , Zhang Zhexin , Ma Xun , Yue Yuanbo , Li Kemu , Meng Yingqi , Wu Yupan
Published: February 2024

The rotation of cells is of significant importance in various applications including bioimaging, biophysical analysis and microsurgery. Current methods usually require complicated fabrication processes. Herein, we proposed an induced charged electroosmosis (ICEO) based on a chip manipulation method for rotating cells. Under an AC electric field, symmetric ICEO flow microvortexes formed above the electrode surface can be used to trap and rotate cells. We have discussed the impact of ICEO and dielectrophoresis (DEP) under the experimental conditions. The capabilities of our method have been tested by investigating the precise rotation of yeast cells and K562 cells in a controllable manner. By adjusting the position of cells, the rotation direction can be changed based on the asymmetric ICEO microvortexes via applying a gate voltage to the gate electrode. Additionally, by applying a pulsed signal instead of a continuous signal, we can also precisely and flexibly rotate cells in a stepwise way. Our ICEO-based rotational manipulation method is an easy to use, biocompatible and low-cost technique, allowing rotation regardless of optical, magnetic or acoustic properties of the sample.
A Narrative Review Exploring Attention Deficit/Hyperactivity Disorder in Patients with Early Psychosis
Authors: Toba-Oluboka Temi , Dempster Kara
Published: February 2024

While both Attention deficit hyperactivity disorder (ADHD) and schizophrenia are considered to have neurodevelopmental origins with associated impairments in executive functioning, there is a paucity of clinical guidelines pertaining specifically to this comorbidity. We sought to summarize the existing literature on ADHD in early psychosis patients, focusing on issues that would be most relevant to clinical practice. For this narrative review, we completed a search on PubMed and PsycINFO with 22 papers meeting criteria for review. Overall, it appears that a diagnosis of ADHD in childhood increases the risk of the subsequent development of a primary psychotic disorder. This risk may be modified by higher rates of substance use and could be related to shared premorbid risk factors for both conditions, such as obstetrical complications. Stimulant use has been associated with the onset of psychotic symptoms in some individuals, but it is unclear whether certain subgroups are more susceptible. Despite the fact that these two conditions co-occur relatively frequently, there is currently a lack of objective diagnostic tests for ADHD specific to populations with primary psychotic disorders, and a paucity of evidence on whether stimulants are effective for ADHD symptoms in this sub-group. Future research is warranted to investigate whether stimulant treatment confers any additional risks for symptom exacerbation in individuals with primary psychotic disorders taking antipsychotic maintenance treatment.
Correction: Gurevitz, M.; Leisman, G. Factors in Infancy That May Predict Autism Spectrum Disorder. Brain Sci. 2023, 13, 1374
Authors: Gurevitz Mina , Leisman Gerry
Published: February 2024

There was an error in the original publication [...]
Advanced Maternal Age: A Scoping Review about the Psychological Impact on Mothers, Infants, and Their Relationship
Authors: Ahmad Monica , Sechi Cristina , Vismara Laura
Published: February 2024

The mean age at childbirth in Europe has gradually increased, and it is now around 29 years of age. It has been shown that older maternal age is associated with problems of fertility; in fact, with increasing age, the chance of conceiving diminishes, and fetal and obstetric complications grow. Research has focused particularly on the biological risks associated with late pregnancy, both for the child and the woman. Less space has been dedicated to the potential psychological and relational benefits of motherhood at an advanced age. The aim of this review was to summarize the existing literature on this issue. Qualitative and quantitative studies were sourced from Pubmed, Science Direct, PsycINFO, and SciELO. The selected works highlight that advanced maternal age can be associated with some advantages for both mothers and their offspring in terms of physical healthcare, parenting styles, and child developmental outcomes. Specifically, the review suggests that older mothers have greater emotional maturity and feel more prepared for motherhood; also, advanced maternal age appears to exert a protective influence on children’s behavioral, social, and emotional functioning, compensating for the biological risks.
How Does Public Service Motivation Affect the Proactive Service Behaviors of Grid Workers? A Study of Survey Evidence from Eastern China
Authors: Chen Lijun , Lin Chuanxue , Zhou Xiaorui
Published: February 2024

In China, grid workers have increasingly become an indispensable and important force in basic social governance. They not only undertake several tasks, such as gaining publicity, collecting information, resolving conflicts, and assisting in management, but they also actively serve the grid residents enthusiastically and engage in proactive service behaviors. In order to better cultivate this important force, we hope to have a better understanding of the factors contributing to the behavioral performance of grid workers, especially the impact of organizational and personal factors. In this study, we sought to establish what factors influence the proactive service behaviors of grid workers. Based on a theoretical consideration of factors such as public service motivation, occupational identity, and organizational climate, a multi-factor influence hypothesis model was constructed to explain the proactive service behaviors of these workers. By analyzing data based on 348 paired survey samples received in two stages in eastern China, these hypotheses were then tested. The results reflect that grid workers’ public service motivation can stimulate proactive service behaviors. Furthermore, occupational identity plays a mediating role, while organizational support and organizational service climate play a positive moderating role between public service motivation and occupational identity. This finding clarifies the important influencing factors of proactive service behaviors among grassroots workers, such as grid workers, and has important implications for how to effectively motivate these groups to provide more proactive services, promoting their sustainable development and improve the effectiveness of grassroots governance.
Social Interoception and Autonomic System Reactivity during Synchronization Behavior
Authors: Balconi Michela , Angioletti Laura
Published: February 2024

Background: Within the social interoception field, little is known about the impact of interoception on autonomic system reactivity during synchronization tasks. The impact of social framing manipulation and Interoceptive Attentiveness (IA; defined as concentrated attention on the breath for a specific time interval) on autonomic responses during interpersonal synchronization was investigated in this research. Methods: Under two experimental interoceptive conditions—the concentration and no focus on the breath condition—participants completed two synchronization tasks. A social framing was given to participants by informing them that they needed to complete the tasks in unison to improve their collaboration abilities. Autonomic responses (electrodermal activity and cardiovascular indices) were collected throughout task performance. Results: Two orders of results were observed: high cognitive engagement was detected during the focus on the breath condition and for the social frame. This effect was specifically observed for the motor compared to the linguistic synchronization task. Meanwhile, a potential lack of emotional control was observed in the no focus on the breath condition when the synchronization tasks were not socially framed. Conclusions: Such results encourage the use of the hyperscanning paradigm to deepen the impact of IA in real-time and ecological interpersonal synchronization dynamics.
Propagation Behavior of P1-Wave Passing through Fluid-Saturated Porous Continuous Barrier in Layered Saturated Soil
Authors: Xu Xunqian , Li Yu , Kang Fengyi , Li Shue , Wan Guozhi , Li Qi , Wu Tao , Wang Siwen
Published: February 2024

The fluid-saturated porous continuous barrier has a better vibration isolation effect than the single-phase solid continuous barrier, and layer-forming saturated soils will have an impact on the vibration isolation effect of the barriers due to their irregular layer-forming distribution. Based on Biot’s theory of saturated porous media and Snell’s law, a dynamic model of a fluid-saturated porous continuous barrier in layered saturated soil is established in this study. By introducing the potential function and using the continuous boundary condition of the interface between the saturated soil and the barrier, the analytical solution of the inverse transmission amplitude ratio of a P1-wave passing through the fluid-saturated porous continuous barrier in stratified saturated soil is obtained. The rationality of the proposed method is verified by comparing the solution of the P-wave model at the interface between the elastic medium and the saturated coarse particle interlayer. The differences in the propagation characteristics of fluid-saturated porous continuous barriers in layered saturated soils, homogeneous saturated soils, and layered single-phase soils are analyzed via numerical examples, and the influence of changes in the physical and mechanical parameters of the fluid-saturated porous continuous barriers on the reflectance amplitude ratios under the conditions of a layered saturated soil foundation are also analyzed. The results show that the presence of fluid in the stratified saturated soil model changes the trend of the reflection amplitude ratio with the incidence angle. The reflection amplitude ratio of the P2-wave and the SV-wave increases first and then decreases with the increase in the incident angle, while the reflection amplitude ratio of P1-wave decreases first and then increases. Barrier thickness and porosity change the energy distribution relationship at the interface; a relatively thicker barrier thickness and a higher porosity would result in a higher amplitude of barrier reflections.
Influence of Mineral Admixtures on the Performance of Pervious Concrete and Microscopic Research
Authors: Yuan Wenhua , Ji Lianjie , Meng Long , Fang Min , Zhang Xiangchi
Published: February 2024

Pervious concrete is an innovative eco-friendly construction material. Through the application of mineral admixtures and microscopic analysis to optimize its performance and analyze its mechanisms, its traits as a sustainable building option may be further improved. This study primarily examines the impact of the optimal blend quantities of fly ash, silica fume, and reinforcing agent on the attributes, micro-morphology, and phase composition of porous concrete. The optimal admixture was chosen after analyzing the effects of various factors on the mix ratio and properties of permeable concrete. To understand the degree of impact, performance tests were conducted on the 28-day compressive strength, water permeability coefficient, and porosity. Furthermore, the micro-mechanisms of the admixtures and reinforcing agents on the properties of permeable concrete were analyzed from a microscopic point of view using scanning electron microscopy (SEM) and X-ray diffraction (XRD) analysis. This research found that the advantageous properties of permeable concrete were enhanced by the simultaneous integration of appropriate quantities of fly ash, silica fume, and reinforcing agent. This resulted in a 28-day compressive strength of 18.33 MPa and a permeability coefficient of 8.27 mm/s. Compared with the unadulterated mineral admixture, the optimal admixture of fly ash, silica fume, and reinforcing agent at the same time increased the 28-day compressive strength by about double; the permeability coefficient was reduced by 36%, but it was still at a high level; and the measured porosity did not differ much from the designed porosity. Through thorough microanalysis, the hydration reaction was significantly improved, which could enhance the microstructure and pore structure of the concrete. This was supported by a substantial increase in the macroscopic compressive strength and a decrease in the water permeability coefficient, which were consistent with the aforementioned enhancement found in the microanalysis.
Greenhouse Gas Emissions in Railways: Systematic Review of Research Progress
Authors: da Fonseca-Soares Diogo , Eliziário Sayonara Andrade , Galvincio Josicleda Domiciano , Ramos-Ridao Angel Fermin
Published: February 2024

Rail transportation plays a crucial role in reducing carbon emissions from the transportation system, making a significant contribution to environmental impact mitigation due to the efficiency of passenger and freight rail transportation. Accurate assessment of carbon emissions resulting from rail transit is essential to quantify the positive impact of this mode of transportation on overall urban transport emission reduction. Given that measuring carbon emissions throughout the lifecycle of rail transportation involves a wide array of factors, adopting a systematic framework for analyzing these aspects is crucial. This study conducts a comprehensive review of existing research related to carbon emissions in rail transportation and its mitigation. Initially, the distinct characteristics of carbon emissions associated with rail transportation are identified, along with the complexity involved in accurately measuring these emissions. Subsequently, a comparison and analysis are conducted regarding various models for measuring carbon emissions in rail transportation. Finally, the study examines some greenhouse gas emission measurement research within the railway system. Redirecting research efforts toward measuring carbon emissions in the rail transportation system is essential to help the development of robust and effective public policies. This measure will play a crucial role in emission reduction, climate change mitigation, and the promotion of more sustainable transportation. Furthermore, the identified results propose which LCA methodology offers a valuable framework improving the quality of railway transportation emissions for future generations.
State-Based Technical Condition Assessment and Prediction of Concrete Box Girder Bridges
Authors: Zhu Zewen , Ye Kuai , Yu Xinhua , Lin Zefang , Xu Gangzong , Guo Zhenyou , Lu Shoushan , Nie Biao , Chen Huapeng
Published: February 2024

The technical condition of bridges has become a crucial issue for organizing the maintenance and repairs in bridge management systems. It is of great practical engineering significance to construct an effective model for predicting the technical condition degradation of the bridge through the use of the historical inspection data. Based on the semi-Markov random process, this paper proposes a useful deterioration prediction model for bridges in the highway network. From the historical inspection data of the prefabricated concrete box girder bridges, the degradation curves of technical condition rating are obtained. The effect of bridge length on degradation rate of the prefabricated concrete box girder bridges is analyzed. According to the Weibull distribution parameters of different condition grades, the technical state degradation models for a bridge group and an individual bridge are proposed to predict the performance of the overall bridge and superstructure of the bridge. The results show that with the increase in bridge length, the degradation rate of bridge technical condition increases. The degradation rate of the technical condition of the superstructure is faster than that of the overall bridge. The proposed semi-Markov stochastic degradation model for the bridge group can not only predict the different condition ratings of the bridges at any time, but also predict the future deterioration trend of an individual bridge under any ratings.
The Impact of China’s New Infrastructure Development on Urban Innovation Quality—A Quasi-Natural Experiment of Smart City Pilots
Authors: Li Ziyan , Xie Shasha , Wei Zhe
Published: February 2024

Currently, human society is in the era of the digital economy, driven by a new wave of digital technology revolution. Against this backdrop, China actively draws on global development concepts, accelerating the advancement of new infrastructure construction. This initiative aims to stabilize current economic demands while laying a material foundation for long-term development. Therefore, the efficient implementation of this new infrastructure has become a pressing issue for China, as unlocking its empowering role in the national economy is of paramount importance. This study, based on balanced panel data from China’s initial smart city pilot projects from 2008 to 2018, employs both two-way fixed effects and mediation effect models to empirically examine the impact of new infrastructure construction on urban innovation quality, considering endogeneity issues. The research findings reveal that new infrastructure construction enhances urban innovation quality by expediting industrial structural upgrades and enhancing total factor productivity. Furthermore, due to variations in geographical location and population density, there is heterogeneity in the impact of new infrastructure on urban innovation quality, with investments in new infrastructure exerting a more pronounced positive effect in cities with high population density.
Influence of Sun Shading Devices on Energy Efficiency, Thermal Comfort and Lighting Comfort in a Warm Semi-Arid Dry Mediterranean Climate
Authors: Pérez-Carramiñana Carlos , González-Avilés Ángel Benigno , Castilla Nuria , Galiano-Garrigós Antonio
Published: February 2024

The dry Mediterranean climate (BShs) is the European region with the highest number of hours of sunshine per year. The high annual solar radiation makes sun shading devices necessary to comply with current energy efficiency standards. However, these standards do not sufficiently consider their effect on the indoor lighting comfort of buildings. The objective is to qualitatively and quantitatively determine how movable sun shading devices jointly influence the energy efficiency, thermal comfort and lighting comfort of buildings in BShs climate. The scientific novelty of the work consists of demonstrating the limitations of the sun shading systems commonly used in southeastern Spain and determining the optimal technical solution in this climate to simultaneously improve thermal and lighting comfort. This research comparatively studies the influence of various movable sun shading systems on the daylighting and thermal performance of an educational building. This study conducted on-site measurements, user surveys and computer simulations to study how to improve the thermal and lighting performances of the building. This work demonstrates that interior solar shading provides little improvement in thermal comfort and reduces the cooling demand by only 25%. External movable sun shading improves thermal comfort and reduces the cooling demand by more than 60%, but only adjustable blinds or awnings achieve adequate and homogeneous illuminance values as they diffuse daylight. The paper concludes that energy efficiency standards should be modified to ensure adequate lighting comfort in buildings.
Do Consumers Have Colour Aesthetic Preferences for the Facade Materials of Condominium Buildings?
Authors: Chen Kaida , Lin Hanliang , Chen Yen-Jong , Xu Yue , Ding Shuhui , Guo Yujie , You Shuying
Published: February 2024

The distinct cultural environment of various regions leads to unique consumer preferences for building facades, including the colours and materials that are used for the exteriors of condominium buildings. Understanding these preferences holds significant industry reference value for urban planning authorities and residential development companies. However, the colour and material aesthetic preferences of consumers for building facades have not received much research attention. To fill this gap, this study empirically investigates these preferences within the cultural context of Fuzhou, China. Using house prices as a reference perspective and econometric methods as research tools, this study explores the specific aesthetic preferences of urban consumer groups and compares the preferences of groups with different levels of consumption. The results confirm the existence of specific consumer preferences for building facade colours and materials and a close connection among the variations in these preferences and various combinations of facade colours and materials. Different quantities and types of materials can lead to distinct preferences for the quantities and features of facade colours. Apart from providing precise professional insights for urban planning authorities and residential developers, this study also offers a feasible conceptual reference for future studies to be conducted in other regions.
Robustness of Reinforced Concrete Slab Structures: Lessons Learned from Two Full-Scale Tests
Authors: Pérez Caldentey Alejandro , G. Diego Yolanda , Santos Anastasio P. , López Lina , Chiquito María , Castedo Ricardo
Published: February 2024

Within the research project ITSAFE, two full-scale structures were built, one consisting of a single-storey, two-span, 7.00 × 14.00 m2 RC frame with a solid slab and another consisting of a two-storey, 7.00 × 7.00 m2 RC frame with solid slabs. In the two-span frame, one of the central supports was first demolished using a pneumatic hammer, resulting in rather limited damage (a 14–15 cm deflection at the removed support location). However, torsional cracks appeared at the interface between a column and slab in one of the outer supports. When the second central support was removed, the structure collapsed with the failure of the support–slab connection. The same type of cracking was observed in the two-storey structure, where the column removal was dynamic, and a 22 cm deflection was measured. These experimental results question current practice in which, for internal supports, alternative load path mobilizing membrane forces in the slab are said to prevent their collapse, or in the cases of edge and corner columns, rupture line analysis is used and suggests that special reinforcement at the column–support connection is also needed to prevent the premature failure of the structure.
External Spatial Morphology of Creative Industries Parks in the Industrial Heritage Category Based on Spatial Syntax: Taking Tianjin as an Example
Authors: Jiang Zhuoran , Qi Zimeng , Chen Lijing , Xu Lei , Wan Da , Burak-Gajewski Piotr , Zawisza Rafal , Liu Li
Published: February 2024

Industrial heritage creative industrial parks are an organic component of historical neighborhood buildings. According to several field visits and surveys of creative industrial parks, it has been found that the external space of some creative industrial parks does not meet the needs of the people. This research primarily investigates the critical factors influencing the usability of external spaces in these revitalization projects. Spatial syntax, a field that has seen considerable advancement in recent years, offers a more scientific approach to understanding spatial relationships. Therefore, this paper employs spatial syntax as its principal methodology. It conducts a quantitative analysis of the external spatial morphology of four creative industrial parks of industrial heritage in Tianjin. The study critically evaluates the syntactic values and identifies issues in the external spatial morphology, including a dearth of cultural elements and limited environmental richness. Furthermore, it provides recommendations for the enhancement of these external spaces. The aim is to furnish data support and strategic insights to invigorate the revitalization efforts of Tianjin’s industrial heritage creative industrial parks.
Analysis of the Evolution Pattern and Regional Conservation of Cultural Heritage from the Perspective of Urban Sustainable Transformation: The Case of Xiamen, China
Authors: Zhang Jiahao , Wang Xuqian , Jiang Lan , Chen Zhihong , Xu Subin , Aoki Nobuo
Published: February 2024

This study focuses on the cultural heritage of Xiamen and uses the spatial analysis method of ArcGIS to analyze the spatiotemporal evolution and distribution characteristics of cultural heritage. Through analysis, we aim to optimize the structure of cultural heritage protection areas and tourism routes in urban planning by analyzing the spatial structure characteristics of Xiamen’s cultural heritage types in various historical periods. The results show that in terms of the time dimension, the existing cultural heritage in Xiamen was mainly built between 1840 and 1949, and the center of cultural heritage shows an overall trend of a “north-south direction”. In terms of spatial dimension, the existing cultural height in Xiamen shows a clustering distribution pattern, with clusters located in the Gulangyu and Xiagang areas of Siming District. According to the period, there is a clear spatial correlation pattern, showing a spatial clustering trend of “strong first and then weak”.
Research on an Intelligent Identification Method for Cable-Stayed Force with a Damper Based on Microwave Radar Measurements
Authors: Li Xiaogang , Huang Xiangsheng , Ding Peng , Wang Qiansong , Wang Qin
Published: February 2024

Aiming at the shortcomings of traditional contact cable force monitoring technology in accuracy, efficiency, and applicability, an assessment method based on microwave radar measurements is proposed to measure a sloping cable with a damper for lengths greater than 200 m in this study. A formula for calculating the cable-stayed force with a damper is derived, and an intelligent cable force monitoring platform is developed based on cloud technology. Based on the Chongqing Nanjimen Railway Bridge, a real bridge test was carried out. It was indicated that the microwave radar method could be used to freely adjust the measurement angle and possessed high applicability and penetration. It significantly improved the measurement accuracy and efficiency of cables with a damper for lengths greater than 200 m. It has good application value for the solution of the problems of complicated operation and high costs in the monitoring of cables with a damper. The formula for calculating the cable force with a damper was proven to be reliable and accurate when compared to the results of direct calculation and the equivalent cable length method. It was able to significantly reduce the calculation error of the cable force caused by the influence of the damper. Additionally, the intelligent cable force monitoring platform was utilized to enhance the level of digitization, providing technical support for the scientific management and maintenance of bridges.
Recent Advances in Neuroblastoma Research
Authors: Johnsen John Inge , Kogner Per
Published: February 2024

Neuroblastoma is a neural crest-derived tumor of the peripheral nervous system that is a leading cause of cancer-related deaths in children [...]
Circulating Tumor Cells: How Far Have We Come with Mining These Seeds of Metastasis?
Authors: Radhakrishnan Vijay , Kaifi Jussuf T. , Suvilesh Kanve N.
Published: February 2024

Circulating tumor cells (CTCs) are cancer cells that slough off from the tumor and circulate in the peripheral blood and lymphatic system as micro metastases that eventually results in macro metastases. Through a simple blood draw, sensitive CTC detection from clinical samples has proven to be a useful tool for determining the prognosis of cancer. Recent technological developments now make it possible to detect CTCs reliably and repeatedly from a simple and straightforward blood test. Multicenter trials to assess the clinical value of CTCs have demonstrated the prognostic value of these cancer cells. Studies on CTCs have filled huge knowledge gap in understanding the process of metastasis since their identification in the late 19th century. However, these rare cancer cells have not been regularly used to tailor precision medicine and or identify novel druggable targets. In this review, we have attempted to summarize the milestones of CTC-based research from the time of identification to molecular characterization. Additionally, the need for a paradigm shift in dissecting these seeds of metastasis and the possible future avenues to improve CTC-based discoveries are also discussed.
Artificial Intelligence-Based Treatment Decisions: A New Era for NSCLC
Authors: Fiste Oraianthi , Gkiozos Ioannis , Charpidou Andriani , Syrigos Nikolaos K.
Published: February 2024

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality among women and men, in developed countries, despite the public health interventions including tobacco-free campaigns, screening and early detection methods, recent therapeutic advances, and ongoing intense research on novel antineoplastic modalities. Targeting oncogenic driver mutations and immune checkpoint inhibition has indeed revolutionized NSCLC treatment, yet there still remains the unmet need for robust and standardized predictive biomarkers to accurately inform clinical decisions. Artificial intelligence (AI) represents the computer-based science concerned with large datasets for complex problem-solving. Its concept has brought a paradigm shift in oncology considering its immense potential for improved diagnosis, treatment guidance, and prognosis. In this review, we present the current state of AI-driven applications on NSCLC management, with a particular focus on radiomics and pathomics, and critically discuss both the existing limitations and future directions in this field. The thoracic oncology community should not be discouraged by the likely long road of AI implementation into daily clinical practice, as its transformative impact on personalized treatment approaches is undeniable.
The Combination of Anti-CD47 Antibody with CTLA4 Blockade Enhances Anti-Tumor Immunity in Non-Small Cell Lung Cancer via Normalization of Tumor Vasculature and Reprogramming of the Immune Microenvironment
Authors: Zhuang Zhan , Zhou Jinglin , Qiu Minglian , Li Jiamian , Lin Zhuangheng , Yi Huihan , Liu Xuerong , Huang Changyu , Tang Binghua , Liu Bo , Li Xu
Published: February 2024

In solid tumors, the formidable anti-tumor impact resulting from blocking the “don’t eat me” signal, arising from CD47–SIRPα interaction, is constrained, especially compared to its efficacy in hematopoietic malignancies. Activating macrophage anti-tumor activity not only necessitates the inhibition of the “don’t eat me” signal, but also the activation of the “eat me” (pre-phagocyte) signal. Intriguingly, the cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) antibody (Ab) has been identified to stimulate Fc receptor-mediated active phagocytes in the tumor microenvironment, thereby generating “eat me” signals. This study postulates that concurrently targeting CD47 and CTLA4 could intensify the anti-tumor effects by simultaneously blocking the “don’t eat me” signal while triggering the “eat me” signal. The experimental data from this investigation confirm that the combined targeting of CD47 and CTLA4 enhances immunity against solid tumors in LLC cell-transplanted tumor-bearing mice. This effect is achieved by reducing myeloid-derived suppressor cell infiltration while increasing the presence of effector memory CD8+ T cells, NK1.1+ CD8+ T cells, and activated natural killer T cells. Meanwhile, combination therapy also alleviated anemia. Mechanistically, the anti-CD47 Ab is shown to upregulate CTLA4 levels in NSCLC cells by regulating Foxp1. Furthermore, targeting CD47 is demonstrated to promote tumor vascular normalization through the heightened infiltration of CD4+ T cells. These findings suggest that the dual targeting of CD47 and CTLA4 exerts anti-tumor effects by orchestrating the “eat me” and “don’t eat me” signals, reshaping the immune microenvironment, and fostering tumor vascular normalization. This combined therapeutic approach emerges as a potent strategy for effectively treating solid tumors.
Preoperative Chronic Inflammation Is a Risk Factor for Postoperative Complications Independent of Body Composition in Gastric Cancer Patients Undergoing Radical Gastrectomy
Authors: Matsui Ryota , Inaki Noriyuki , Tsuji Toshikatsu , Fukunaga Tetsu
Published: February 2024

The purpose of this study was to investigate the association between preoperative inflammation and postoperative complications in gastric cancer patients having elective gastrectomy. Participants in this study were those who underwent radical gastrectomy between April 2008 and June 2018 and were diagnosed with stage I–III primary gastric cancer. Preoperative CRP values were used to divide the patients into two groups: the inflammation group comprised individuals having a CRP level of ≥0.5 mg/dL; the other was the non-inflammation group. The primary outcome was overall complications of Clavien–Dindo grade II or higher after surgery. Using propensity score matching to adjust for background, we compared the postoperative outcomes of the groups and conducted a multivariate analysis to identify risk variables for complications. Of 951 patients, 852 (89.6%) were in the non-inflammation group and 99 (10.4%) were in the inflammation group. After matching, both groups included 99 patients, and no significant differences in patient characteristics were observed between both groups. The inflammation group had a significantly greater total number of postoperative complications (p = 0.019). The multivariate analysis revealed that a preoperative CRP level of ≥0.5 mg/dL was an independent risk factor for total postoperative complications in all patients (odds ratio: 2.310, 95% confidence interval: 1.430–3.730, p < 0.001). In conclusion, in patients undergoing curative resection for gastric cancer, preoperative inflammation has been found to be an independent risk factor for overall complications after surgery. Patients with chronic inflammation require preoperative treatment to reduce inflammation because chronic inflammation is the greatest risk factor for postoperative complications.
Atypical Ductal Hyperplasia and Lobular In Situ Neoplasm: High-Risk Lesions Challenging Breast Cancer Prevention
Authors: Nicosia Luca , Mariano Luciano , Pellegrino Giuseppe , Ferrari Federica , Pesapane Filippo , Bozzini Anna Carla , Frassoni Samuele , Bagnardi Vincenzo , Pupo Davide , Mazzarol Giovanni , De Camilli Elisa , Sangalli Claudia , Venturini Massimo , Pizzamiglio Maria , Cassano Enrico
Published: February 2024

This retrospective study investigates the histopathological outcomes, upgrade rates, and disease-free survival (DFS) of high-risk breast lesions, including atypical ductal hyperplasia (ADH or DIN1b) and lobular in situ neoplasms (LIN), following Vacuum-Assisted Breast Biopsy (VABB) and surgical excision. The study addresses the challenge posed by these lesions due to their association with synchronous or adjacent Breast Cancer (BC) and increased future BC risk. The research, comprising 320 patients who underwent stereotactic VABB, focuses on 246 individuals with a diagnosis of ADH (120) or LIN (126) observed at follow-up. Pathological assessments, categorized by the UK B-coding system, were conducted, and biopsy samples were compared with corresponding excision specimens to determine upgrade rates for in situ or invasive carcinoma. Surgical excision was consistently performed for diagnosed ADH or LIN. Finally, patient follow-ups were assessed and compared between LIN and ADH groups to identify recurrence signs, defined as histologically confirmed breast lesions on either the same or opposite side. The results reveal that 176 (71.5%) patients showed no upgrade post-surgery, with ADH exhibiting a higher upgrade rate to in situ pathology than LIN1 (Atypical Lobular Hyperplasia, ALH)/LIN2 (Low-Grade Lobular in situ Carcinoma, LCIS) (38% vs. 20%, respectively, p-value = 0.002). Considering only patients without upgrade, DFS at 10 years was 77%, 64%, and 72% for ADH, LIN1, and LIN2 patients, respectively (p-value = 0.92). The study underscores the importance of a multidisciplinary approach, recognizing the evolving role of VABB. It emphasizes the need for careful follow-up, particularly for lobular lesions, offering valuable insights for clinicians navigating the complex landscape of high-risk breast lesions. The findings advocate for heightened awareness and vigilance in managing these lesions, contributing to the ongoing refinement of clinical strategies in BC care.
The Coexistence of Cervical Intraepithelial Neoplasia (CIN3) and Adenocarcinoma In Situ (AIS) in LEEP Excisions Performed for CIN3
Authors: Bruno Maria Teresa , Valenti Gaetano , Cassaro Nazario , Palermo Ilenia , Incognito Giosuè Giordano , Cavallaro Antonino Giovanni , Sgalambro Francesco , Panella Marco Marzio , Mereu Liliana
Published: February 2024

The purpose of this study was to evaluate the incidence of AIS and AC in the histological cone of women treated for CIN3. Furthermore, through the study of the specific HR HPV genotypes, we obtained more information on the possible different nature between the single CIN3 lesion and the CIN3 coexisting with the glandular lesion. Methods. A sample of 414 women underwent LEEP for CIN3. The study sample consisted of 370 women with a CIN3 lesion alone and 44 women with a CIN3 lesion coexisting with AIS or adenocarcinoma. We studied the individual HR HPV genotypes and their frequency in the two groups under study. Furthermore, the therapeutic results and follow-ups for the population were studied on the entire study sample. Results. In patients with a single CIN3 lesion, 11 high-risk genotypes were detected; in patients with CIN3 associated with AIS or AC, only 4 different genotypes were detected (16, 18, 45, 33). Overall, the frequency of HPV 18 was significantly higher in CIN3 coexisting with AIS compared to solitary CIN3 lesions, χ2 = 27.73 (p < 0.001), while the frequency of other high-risk genotypes was significantly higher in patients with a single CIN3 than in patients with CIN3 coexisting with AIS. In our study population, mixed lesions (CIN3 coexisting with AIS), unlike their squamous counterparts (single CIN3 lesions), were characterized by skip lesions, which demonstrate more aggressive behavior and a higher rate of viral persistence and recurrence. Conclusion. A relatively high rate (10.7%) of AIS-AC was found in women treated for CIN3. Our study confirms the multifocal biological nature of the CIN3 lesion coexisting with AIS compared to the single CIN3 lesion. All this justifies the different treatments to which CIN3 lesions coexisting with AIS are addressed; in fact, the latter are treated with hysterectomy, while CIN3 is treated with conization alone.
Lynch Syndrome: From Multidisciplinary Management to Precision Prevention
Authors: Dal Buono Arianna , Puccini Alberto , Franchellucci Gianluca , Airoldi Marco , Bartolini Michela , Bianchi Paolo , Santoro Armando , Repici Alessandro , Hassan Cesare
Published: February 2024

Background and Aims: Lynch syndrome (LS) is currently one of the most prevalent hereditary cancer conditions, accounting for 3% of all colorectal cancers and for up to 15% of those with DNA mismatch repair (MMR) deficiency, and it was one of the first historically identified. The understanding of the molecular carcinogenesis of LS tumors has progressed significantly in recent years. We aim to review the most recent advances in LS research and explore genotype-based approaches in surveillance, personalized cancer prevention, and treatment strategies. Methods: PubMed was searched to identify relevant studies, conducted up to December 2023, investigating molecular carcinogenesis in LS, surveillance strategies, cancer prevention, and treatment in LS tumors. Results: Multigene panel sequencing is becoming the benchmark in the diagnosis of LS, allowing for the detection of a pathogenic constitutional variant in one of the MMR genes. Emerging data from randomized controlled trials suggest possible preventive roles of resistant starch and/or aspirin in LS. Vaccination with immunogenic frameshift peptides appears to be a promising approach for both the treatment and prevention of LS-associated cancers, as evidenced by pre-clinical and preliminary phase 1/2a studies. Conclusions: Although robust diagnostic algorithms, including prompt testing of tumor tissue for MMR defects and referral for genetic counselling, currently exist for suspected LS in CRC patients, the indications for LS screening in cancer-free individuals still need to be refined and standardized. Investigation into additional genetic and non-genetic factors that may explain residual rates of interval cancers, even in properly screened populations, would allow for more tailored preventive strategies.