bluuebunny/crossref_metadata_2025 huggingface dataset:
A Disease-Prediction Protocol Integrating Triage Priority and BERT-Based Transfer Learning for Intelligent Triage
Authors: Wang Boran , Gao Zhuliang , Lin Zhikang , Wang Rui
Published: March 2023

Large hospitals can be complex, with numerous discipline and subspecialty settings. Patients may have limited medical knowledge, making it difficult for them to determine which department to visit. As a result, visits to the wrong departments and unnecessary appointments are common. To address this issue, modern hospitals require a remote system capable of performing intelligent triage, enabling patients to perform self-service triage. To address the challenges outlined above, this study presents an intelligent triage system based on transfer learning, capable of processing multilabel neurological medical texts. The system predicts a diagnosis and corresponding department based on the patient’s input. It utilizes the triage priority (TP) method to label diagnostic combinations found in medical records, converting a multilabel problem into a single-label one. The system considers disease severity and reduces the “class overlapping” of the dataset. The BERT model classifies the chief complaint text, predicting a primary diagnosis corresponding to the complaint. To address data imbalance, a composite loss function based on cost-sensitive learning is added to the BERT architecture. The study results indicate that the TP method achieves a classification accuracy of 87.47% on medical record text, outperforming other problem transformation methods. By incorporating the composite loss function, the system’s accuracy rate improves to 88.38% surpassing other loss functions. Compared to traditional methods, this system does not introduce significant complexity, yet substantially improves triage accuracy, reduces patient input confusion, and enhances hospital triage capabilities, ultimately improving the patient’s medical experience. The findings could provide a reference for intelligent triage development.
Integrative Analysis of the Predictive Value of Perilipin Family on Clinical Significance, Prognosis and Immunotherapy of Glioma
Authors: Li Xuanxuan , Kang Kuo , Shen Lin , Shen Liangfang , Zhou Yangying
Published: March 2023

Gliomas are common tumors of the central nervous system. The PLINs family is widely involved in the regulation of lipid metabolism and has been associated with the development and invasive metastasis of various malignancies. However, the biological role of the PLINs family in gliomas is still unclear. TIMER and UALCAN were used to assess PLINs mRNA expression in gliomas. “Survminer” and “Survival” were used to evaluate the connection between PLINs expression and glioma patients’ survival. cBioPortal was applied to assess PLINs’ genetic alterations in glioblastoma multiforme (GBM) and low-grade glioma (LGG). The correlation of PLINs expression with tumor immune cells was analyzed by TIMER. The expressions of PLIN1, PLIN4, and PLIN5 were decreased in GBM compared to normal tissues. However, PLIN2 and PLIN3 were significantly increased in GBM. Prognostic analysis showed that LGG patients with high PLIN1 expression had better overall survival (OS), and high expression of PLIN2/3/4/5 was associated with unfavorable OS. We further determined that the expression of PLINs members in gliomas was strongly related to tumor immune cells and immune checkpoint-associated genes. PLINS may be potential biomarkers for regulating the tumor microenvironment and predicting the efficacy of immunotherapy. In addition, we determined that PLIN1 may affect glioma patients’ therapeutic sensitivity to temozolomide. Our results demonstrated the biological significance and clinical values of PLINs in gliomas and provide a basis for future in-depth exploration of the specific mechanisms of each member of PLINs in gliomas.
Differential Activation of NRF2 Signaling Pathway in Renal-Cell Carcinoma Caki Cell Lines
Authors: Hitefield Naomi L. , Mackay Stephen , Hays Lauren E. , Chen Shimin , Oduor Ian O. , Troyer Dean A. , Nyalwidhe Julius O.
Published: March 2023

Renal-cell carcinoma (RCC) is a heterogeneous disease consisting of several subtypes based on specific genomic profiles and histological and clinical characteristics. The subtype with the highest prevalence is clear-cell RCC (ccRCC), next is papillary RCC (pRCC), and then chromophobe RCC (chRCC). The ccRCC cell lines are further subdivided into prognostic expression-based subtypes ccA or ccB. This heterogeneity necessitates the development, availability, and utilization of cell line models with the correct disease phenotypic characteristics for RCC research. In this study, we focused on characterizing proteomic differences between the Caki-1 and Caki-2 cell lines that are commonly used in ccRCC research. Both cells are primarily defined as human ccRCC cell lines. Caki-1 cell lines are metastatic, harboring wild-type VHL, whereas Caki-2 are considered as the primary ccRCC cell lines expressing wild-type von Hippel–Lindau protein (pVHL). Here, we performed a comprehensive comparative proteomic analysis of Caki-1 and Caki-2 cells using tandem mass-tag reagents together with liquid chromatography mass spectrometry (LC/MS) for the identification and quantitation of proteins in the two cell lines. Differential regulation of a subset of the proteins identified was validated using orthogonal methods including western blot, q-PCR, and immunofluorescence assays. Integrative bioinformatic analysis identifies the activation/inhibition of specific molecular pathways, upstream regulators, and causal networks that are uniquely regulated and associated with the two cell lines and RCC subtypes, and potentially the disease stage. Altogether, we have identified multiple molecular pathways, including NRF2 signaling, which is the most significantly activated pathway in Caki-2 versus Caki-1 cells. Some of the differentially regulated molecules and signaling pathways could serve as potential diagnostic and prognostic biomarkers and therapeutic targets amongst ccRCC subtypes.
Intestinal Damage, Inflammation and Microbiota Alteration during COVID-19 Infection
Authors: Saviano Angela , Brigida Mattia , Petruzziello Carmine , Zanza Christian , Candelli Marcello , Morabito Loprete Maria Rita , Saleem Faiz , Ojetti Veronica
Published: March 2023

Background: The virus SARS-CoV-2 is responsible for respiratory disorders due to the fact that it mainly infects the respiratory tract using the Angiotensin-converting enzyme 2 (ACE2) receptors. ACE2 receptors are also highly expressed on intestinal cells, representing an important site of entry for the virus in the gut. Literature studies underlined that the virus infects and replicates in the gut epithelial cells, causing gastrointestinal symptoms such as diarrhea, abdominal pain, nausea/vomiting and anorexia. Moreover, the SARS-CoV-2 virus settles into the bloodstream, hyperactivating the platelets and cytokine storms and causing gut–blood barrier damage with an alteration of the gut microbiota, intestinal cell injury, intestinal vessel thrombosis leading to malabsorption, malnutrition, an increasing disease severity and mortality with short and long-period sequelae. Conclusion: This review summarizes the data on how SARS-CoV-2 effects on the gastrointestinal systems, including the mechanisms of inflammation, relationship with the gut microbiota, endoscopic patterns, and the role of fecal calprotectin, confirming the importance of the digestive system in clinical practice for the diagnosis and follow-up of SARS-CoV-2 infection.
Fecal Microbiota Transplantation in Inflammatory Bowel Disease
Authors: Boicean Adrian , Birlutiu Victoria , Ichim Cristian , Anderco Paula , Birsan Sabrina
Published: March 2023

Inflammatory bowel diseases represent a complex array of diseases of incompletely known etiology that led to gastrointestinal tract chronic inflammation. In inflammatory bowel disease, a promising method of treatment is represented by fecal microbiota transplantation (FMT), FMT has shown its increasing effectiveness and safety in recent years for recurrent CDI; moreover, it showed real clinical benefits in treating SARS-CoV-2 and CDI co-infection. Crohn’s disease and ulcerative colitis are characterized by immune dysregulation, resulting in digestive tract damage caused by immune responses. Most current therapeutic strategies are associated with high costs and many adverse effects by directly targeting the immune response, so modifying the microbial environment by FMT offers an alternative approach that could indirectly influence the host’s immune system in a safe way. Studies outline the endoscopic and clinical improvements in UC and CD in FMT patients versus control groups. This review outlines the multiple benefits of FMT in the case of IBD by improving patients unbalanced gut, therefore improving endoscopic and clinical symptomatology. We aim to emphasize the clinical importance and benefits of FMT in order to prevent flares or complications of IBD and to highlight that further validation is needed for establishing a clinical protocol for FMT in IBD.
Outcomes of a QST Protocol in Healthy Subjects and Chronic Pain Patients: A Controlled Clinical Trial
Authors: Dias Patrícia , Tavares Isaura , Fonseca Sara , Pozza Daniel Humberto
Published: March 2023

Chronic pain is an important cause of disability with a high burden to society. Quantitative sensory testing (QST) is a noninvasive multimodal method used to discriminate the function of nerve fibers. The aim of this study is to propose a new, reproducible, and less time-consuming thermal QST protocol to help characterize and monitor pain. Additionally, this study also compared QST outcomes between healthy and chronic pain subjects. Forty healthy young/adult medical students and fifty adult/elderly chronic pain patients were evaluated in individual sessions including pain history, followed by QST assessments divided into three proposed tests: pain threshold, suprathreshold, and tonic pain. In the chronic pain group, a significantly higher pain threshold (hypoesthesia) and a higher pain sensibility (hyperalgesia) were demonstrated at threshold temperature when compared to healthy participants. The sensitivity to the suprathreshold and tonic stimulus did not prove to be significantly different between both groups. The main results demonstrated that the heat threshold QST tests can be helpful in evaluating hypoesthesia and that the sensitivity threshold temperature test can demonstrate hyperalgesia in individuals with chronic pain. In conclusion, this study demonstrates the importance of using tools such as QST as a complement to detect changes in several pain dimensions.
A Computational Fluid Dynamics Investigation of a Flapping Hydrofoil as a Thruster
Authors: Alberti Luca , Carnevali Emanuele , Costa Daniele , Crivellini Andrea
Published: March 2023

The paper features a computational fluid dynamics study of a flapping NACA0015 hydrofoil moving with a combination of sinusoidal heaving and pitching. Several kinematic configurations are explored, varying sequentially pitch and heave amplitude, Strouhal number and phase angle, in an attempt to determine the influence of each parameter on the propulsive performance. To optimize efficiency the angle of attack should assume the highest value that also avoids the arise of the leading edge vortex generated in the dynamic stall state. At low Strouhal number optimum is reached at high heave amplitudes, which correspond to the configurations minimizing the hysteresis in the (Cy,Cx) plane. The same outcome in terms of hysteresis minimization has been verified to occur when optimal phase shift was considered. Differently, when the Strouhal number and the angle of attack become higher, to exploit efficiently the lift increment owed to dynamic stall it emerged the necessity of adopting low heave amplitude to improve separation resistance, avoiding the occurrence of deep stall.
New Generation Dielectrophoretic-Based Microfluidic Device for Multi-Type Cell Separation
Authors: Sharbati Pouya , Sadaghiani Abdolali K. , Koşar Ali
Published: March 2023

This study introduces a new generation of dielectrophoretic-based microfluidic device for the precise separation of multiple particle/cell types. The device features two sets of 3D electrodes, namely cylindrical and sidewall electrodes. The main channel of the device terminates with three outlets: one in the middle for particles that sense negative dielectrophoresis force and two others at the right and left sides for particles that sense positive dielectrophoresis force. To evaluate the device performance, we used red blood cells (RBCs), T-cells, U937-MC cells, and Clostridium difficile bacteria as our test subjects. Our results demonstrate that the proposed microfluidic device could accurately separate bioparticles in two steps, with sidewall electrodes of 200 µm proving optimal for efficient separation. Applying different voltages for each separation step, we found that the device performed most effectively at 6 Vp-p applied to the 3D electrodes, and at 20 Vp-p and 11 Vp-p applied to the sidewall electrodes for separating RBCs from bacteria and T-cells from U937-MC cells, respectively. Notably, the device’s maximum electric fields remained below the cell electroporation threshold, and we achieved a separation efficiency of 95.5% for multi-type particle separation. Our findings proved the device’s capacity for separating multiple particle types with high accuracy, without limitation for particle variety.
Trends in Paper-Based Sensing Devices for Clinical and Environmental Monitoring
Authors: Kummari Shekher , Panicker Lakshmi R. , Rao Bommi Jagadeeswara , Karingula Sampath , Sunil Kumar Venisheety , Mahato Kuldeep , Goud Kotagiri Yugender
Published: March 2023

Environmental toxic pollutants and pathogens that enter the ecosystem are major global issues. Detection of these toxic chemicals/pollutants and the diagnosis of a disease is a first step in efficiently controlling their contamination and spread, respectively. Various analytical techniques are available to detect and determine toxic chemicals/pathogens, including liquid chromatography, HPLC, mass spectroscopy, and enzyme-linked immunosorbent assays. However, these sensing strategies have some drawbacks such as tedious sample pretreatment and preparation, the requirement for skilled technicians, and dependence on large laboratory-based instruments. Alternatively, biosensors, especially paper-based sensors, could be used extensively and are a cost-effective alternative to conventional laboratory testing. They can improve accessibility to testing to identify chemicals and pollutants, especially in developing countries. Due to its low cost, abundance, easy disposal (by incineration, for example) and biocompatible nature, paper is considered a versatile material for the development of environmentally friendly electrochemical/optical (bio) sensor devices. This review presents an overview of sensing platforms constructed from paper, pointing out the main merits and demerits of paper-based sensing systems, their fabrication techniques, and the different optical/electrochemical detection techniques that they exploit.
Biophysical Sensors Based on Triboelectric Nanogenerators
Authors: Ma Zimeng , Cao Xia , Wang Ning
Published: March 2023

Triboelectric nanogenerators (TENGs) can not only collect mechanical energy around or inside the human body and convert it into electricity but also help monitor our body and the world by providing interpretable electrical signals during energy conversion, thus emerging as an innovative medical solution for both daily health monitoring and clinical treatment and bringing great convenience. This review tries to introduce the latest technological progress of TENGs for applications in biophysical sensors, where a TENG functions as a either a sensor or a power source, and in some cases, as both parts of a self-powered sensor system. From this perspective, this review begins from the fundamental working principles and then concisely illustrates the recent progress of TENGs given structural design, surface modification, and materials selection toward output enhancement and medical application flexibility. After this, the medical applications of TENGs in respiratory status, cardiovascular disease, and human rehabilitation are covered in detail, in the form of either textile or implantable parts for pacemakers, nerve stimulators, and nerve prostheses. In addition, the application of TENGs in driving third-party medical treatment systems is introduced. Finally, shortcomings and challenges in TENG-based biophysical sensors are highlighted, aiming to provide deeper insight into TENG-based medical solutions for the development of TENG-based self-powered electronics with higher performance for practical applications.
Exploring Monocytes-Macrophages in Immune Microenvironment of Glioblastoma for the Design of Novel Therapeutic Strategies
Authors: Caverzán Matías Daniel , Beaugé Lucía , Oliveda Paula Martina , Cesca González Bruno , Bühler Eugenia Micaela , Ibarra Luis Exequiel
Published: March 2023

Gliomas are primary malignant brain tumors. These tumors seem to be more and more frequent, not only because of a true increase in their incidence, but also due to the increase in life expectancy of the general population. Among gliomas, malignant gliomas and more specifically glioblastomas (GBM) are a challenge in their diagnosis and treatment. There are few effective therapies for these tumors, and patients with GBM fare poorly, even after aggressive surgery, chemotherapy, and radiation. Over the last decade, it is now appreciated that these tumors are composed of numerous distinct tumoral and non-tumoral cell populations, which could each influence the overall tumor biology and response to therapies. Monocytes have been proved to actively participate in tumor growth, giving rise to the support of tumor-associated macrophages (TAMs). In GBM, TAMs represent up to one half of the tumor mass cells, including both infiltrating macrophages and resident brain microglia. Infiltrating macrophages/monocytes constituted ~ 85% of the total TAM population, they have immune functions, and they can release a wide array of growth factors and cytokines in response to those factors produced by tumor and non-tumor cells from the tumor microenvironment (TME). A brief review of the literature shows that this cell population has been increasingly studied in GBM TME to understand its role in tumor progression and therapeutic resistance. Through the knowledge of its biology and protumoral function, the development of therapeutic strategies that employ their recruitment as well as the modulation of their immunological phenotype, and even the eradication of the cell population, can be harnessed for therapeutic benefit. This revision aims to summarize GBM TME and localization in tumor niches with special focus on TAM population, its origin and functions in tumor progression and resistance to conventional and experimental GBM treatments. Moreover, recent advances on the development of TAM cell targeting and new cellular therapeutic strategies based on monocyte/macrophages recruitment to eradicate GBM are discussed as complementary therapeutics.
The Effects of Four Compounds That Act on the Dopaminergic and Serotonergic Systems on Working Memory in Animal Studies; A Literature Review
Authors: Grosu Ștefania-Alexandra , Chirilă Marinela , Rad Florina , Enache Andreea , Handra Claudia-Mariana , Ghiță Isabel
Published: March 2023

The dopaminergic and serotonergic systems are two of the most important neuronal pathways in the human brain. Almost all psychotropic medications impact at least one neurotransmitter system. As a result, investigating how they affect memory could yield valuable insights into potential therapeutic applications or unanticipated side effects. The aim of this literature review was to collect literature data from animal studies regarding the effects on memory of four drugs known to act on the serotonergic and dopaminergic systems. The studies included in this review were identified in the PubMed database using selection criteria from the PRISMA protocol. We analyzed 29 articles investigating one of four different dopaminergic or serotonergic compounds. Studies conducted on bromocriptine have shown that stimulating D2 receptors may enhance working memory in rodents, whereas inhibiting these receptors could have the opposite effect, reducing working memory performance. The effects of serotonin on working memory are not clearly established as studies on fluoxetine and ketanserin have yielded conflicting results. Further studies with better-designed methodologies are necessary to explore the impact of compounds that affect both the dopaminergic and serotonergic systems on working memory.
Electroencephalography Based Microstate Functional Connectivity Analysis in Emotional Cognitive Reappraisal Combined with Happy Music
Authors: Hua Wangchun , Li Yingjie
Published: March 2023

Currently, research mainly focuses on the effects of happy music on the subjective assessment of cognitive reappraisal, but relevant results of the neural mechanism are lacking. By analysing the functional connectivity of microstates based on electroencephalography (EEG), we investigated the effect of cognitive reappraisal combined with happy music on emotional regulation and the dynamic characteristics of brain functional activities. A total of 52 healthy college students were divided into music group and control group. EEG data and behavioural scores were collected during an experiment of cognitive reappraisal combined with happy music. The dynamic time window of the brain functional network was determined by microstate analysis, and the metrics of functional connectivity, clustering coefficient (Cp) and characteristic path length (Lp), were calculated based on the phase-locked value. The arousal of cognitive reappraisal significantly increased (p = 0.005) in music group, but the valence did not change significantly. This suggested that happy music did not affect emotional regulation from the behavioural perspective. Four microstate global templates (A–D) were determined. With happy music, the duration (p = 0.043) and Lp (p = 0.033) of microstate B increased significantly, indicating that the transfection efficiency of the brain network decreased, reflecting a negative effect on cognitive reappraisal. The duration (p = 0.017) of microstate D decreased and of Cp (p < 0.001) increased significantly, indicating that the local information-processing ability of the brain network increased. We conclude that happy music can change the characteristics of brain functional networks and have a positive effect on cognitive reappraisal in specific period. The research provides a certain electrophysiological basis for applying happy music to cognitive reappraisal.
Lie Recognition with Multi-Modal Spatial–Temporal State Transition Patterns Based on Hybrid Convolutional Neural Network–Bidirectional Long Short-Term Memory
Authors: Abdullahi Sunusi Bala , Bature Zakariyya Abdullahi , Gabralla Lubna A. , Chiroma Haruna
Published: March 2023

Recognition of lying is a more complex cognitive process than truth-telling because of the presence of involuntary cognitive cues that are useful to lie recognition. Researchers have proposed different approaches in the literature to solve the problem of lie recognition from either handcrafted and/or automatic lie features during court trials and police interrogations. Unfortunately, due to the cognitive complexity and the lack of involuntary cues related to lying features, the performances of these approaches suffer and their generalization ability is limited. To improve performance, this study proposed state transition patterns based on hands, body motions, and eye blinking features from real-life court trial videos. Each video frame is represented according to a computed threshold value among neighboring pixels to extract spatial–temporal state transition patterns (STSTP) of the hand and face poses as involuntary cues using fully connected convolution neural network layers optimized with the weights of ResNet-152 learning. In addition, this study computed an eye aspect ratio model to obtain eye blinking features. These features were fused together as a single multi-modal STSTP feature model. The model was built using the enhanced calculated weight of bidirectional long short-term memory. The proposed approach was evaluated by comparing its performance with current state-of-the-art methods. It was found that the proposed approach improves the performance of detecting lies.
Interpretable Machine Learning Model Predicting Early Neurological Deterioration in Ischemic Stroke Patients Treated with Mechanical Thrombectomy: A Retrospective Study
Authors: Yang Tongtong , Hu Yixing , Pan Xiding , Lou Sheng , Zou Jianjun , Deng Qiwen , Zhang Qingxiu , Zhou Junshan , Zhu Junrong
Published: March 2023

Early neurologic deterioration (END) is a common and feared complication for acute ischemic stroke (AIS) patients treated with mechanical thrombectomy (MT). This study aimed to develop an interpretable machine learning (ML) model for individualized prediction to predict END in AIS patients treated with MT. The retrospective cohort of AIS patients who underwent MT was from two hospitals. ML methods applied include logistic regression (LR), random forest (RF), support vector machine (SVM), and extreme gradient boosting (XGBoost). The area under the receiver operating characteristic curve (AUC) was the main evaluation metric used. We also used Shapley Additive Explanation (SHAP) and Local Interpretable Model-Agnostic Explanations (LIME) to interpret the result of the prediction model. A total of 985 patients were enrolled in this study, and the development of END was noted in 157 patients (15.9%). Among the used models, XGBoost had the highest prediction power (AUC = 0.826, 95% CI 0.781–0.871). The Delong test and calibration curve indicated that XGBoost significantly surpassed those of the other models in prediction. In addition, the AUC in the validating set was 0.846, which showed a good performance of the XGBoost. The SHAP method revealed that blood glucose was the most important predictor variable. The constructed interpretable ML model can be used to predict the risk probability of END after MT in AIS patients. It may help clinical decision making in the perioperative period of AIS patients treated with MT.
Elderly Users’ Emotional and Behavioral Responses to Self-Service Technology in Fast-Food Restaurants
Authors: Nam Jinyoung , Kim Seongcheol , Jung Yoonhyuk
Published: March 2023

While COVID-19 has accelerated digital transformation, increasing labor costs and 52-h workweek rules are replacing human labor with self-service technologies (SSTs). Self-service technology is increasingly being implemented in restaurant settings. However, the elderly, who have relatively lower levels of digital literacy, are being excluded from services that can alleviate the economic and social difficulties of their daily lives. This study thus aims to explain how elderly users feel about and respond to SST in fast-food restaurants. An off-site survey was conducted with individuals who had experience using SST. We analyzed the data using the partial least squares structural equation modeling method by SmartPLS 3.0. The results showed that SST’s reduction, perceived ease of use of SST, and perceived time pressure significantly influenced users’ negative emotions toward the SST. However, perceived physical condition and perceived crowding did not have significant influences on users’ emotions. In empirically investigating individuals’ negative emotions toward and coping strategies for challenges posed by SST, this study emphasizes the development of a nationwide digital inclusion policy that can help bridge the digital divide.
Computer Vision Observation for Progressive Failure Characteristics of a Moderately Weathered Red Mudstone Foundation: Design and Experiment
Authors: Bai Yu , Hu Qijun , Feng Shiqing , Zheng Lining , He Leping , Wang Yichun
Published: March 2023

The bearing stratum of high-rise and ultra-high-rise buildings in southwest China has inevitably faced moderately weathered red mudstone. It was a waste of the potential bearing stratum calculated according to the specification, as the bearing stratum obtained from laboratory and in situ tests was much higher than the values suggested by the specification. Rock mass surface deformation detection is of great significance in the safety management of a foundation project. Some correlation between surface deformation and failure characteristics may exist that could help to understand the bearing stratum of the moderately weathered red mudstone. This research was conducted to study the progressive failure characteristics of the moderately weathered red mudstone through surface deformation. In situ load, triaxial, and binocular visual technology were employed for data acquisition. The proposed conjecture was illustrated and verified by a group of experiments from three construction sites. Five stages could be described as the progressive failure of the moderately weathered red mudstone: compaction, elasticity, elastoplasticity, plasticity, and failure. Furthermore, the surface displacement increment fluctuates with the loading time and fades into the distance. Therefore, this research could provide a robust, practical application for analyzing the progressive failure of moderately weathered red mudstone.
Algorithm-Aided Design for Composite Bridges
Authors: Boretti Valentina , Sardone Laura , Bohórquez Graterón Luis Alberto , Masera Davide , Marano Giuseppe Carlo , Domaneschi Marco
Published: March 2023

Bridges are geometrically complex infrastructures, and their designs usually exhibit significant geometric variations between different structural solutions. The modelling complexity implies a low degree of model reuse in comparable projects; moreover, with the development of new technologies and design ways, the AEC industry often requires computational cost reduction, less time for model developments and analysis, and little-to-zero material waste in the face of the environmental emergency. The present document proposes a generative approach to enhance the bridge design process, increasing efficiency by reducing computational costs and modelling efforts, tackling the aforementioned objectives. The following methodology relies on a workflow to create flexible geometric models, introducing parameters and numerical relationships between all the design variables. Therefore, from a generative development, different geometric solutions of a bridge’s family are created by modifying the parameter settings within the same model. Then, the present work aims to define a modelling and analysis strategy for a multi-girder composite bridge project based on parametric development, structural analysis, and optimization. The results integrate building information modeling (BIM) to explore and create high-potential designs with complex geometries and find cost-effective solutions.
Transmitting Culture through Building Systems: The Case of the Tile Vault
Authors: Alcindor Mónica , Jackson Delton
Published: March 2023

Until now, the technology behind building systems has largely been neglected, and an exploration of the cultural transmission of these systems has been undervalued as a way of understanding changes in the symbolic worldview of society. This article analyses the developmental transitions in a specific building system, specifically the tile vault, as a case study that illustrates the changing values of a construction process as it has evolved, together with an understanding of the philosophy that has accompanied those changes over time. An ethnohistorical and ethnographic method has been used, enabling a longitudinal and rich analysis through time that illustrates the indissolubility of the technical issues from the prevailing social institutions of each era. These are based on a careful reading of changing conditions (environmental, social, and cultural), and of the progressive participatory appropriation which takes place through cooperative, synergistic working.
Chondrosarcoma Resistance to Radiation Therapy: Origins and Potential Therapeutic Solutions
Authors: Gilbert Antoine , Tudor Mihaela , Montanari Juliette , Commenchail Kevin , Savu Diana Iulia , Lesueur Paul , Chevalier François
Published: March 2023

Chondrosarcoma is a malignant cartilaginous tumor that is particularly chemoresistant and radioresistant to X-rays. The first line of treatment is surgery, though this is almost impossible in some specific locations. Such resistances can be explained by the particular composition of the tumor, which develops within a dense cartilaginous matrix, producing a resistant area where the oxygen tension is very low. This microenvironment forces the cells to adapt and dedifferentiate into cancer stem cells, which are described to be more resistant to conventional treatments. One of the main avenues considered to treat this type of tumor is hadrontherapy, in particular for its ballistic properties but also its greater biological effectiveness against tumor cells. In this review, we describe the different forms of chondrosarcoma resistance and how hadrontherapy, combined with other treatments involving targeted inhibitors, could help to better treat high-grade chondrosarcoma.
The Battlefield of Chemotherapy in Pediatric Cancers
Authors: Bo Letao , Wang Youyou , Li Yidong , Wurpel John N. D. , Huang Zoufang , Chen Zhe-Sheng
Published: March 2023

The survival rate for pediatric cancers has remarkably improved in recent years. Conventional chemotherapy plays a crucial role in treating pediatric cancers, especially in low- and middle-income countries where access to advanced treatments may be limited. The Food and Drug Administration (FDA) approved chemotherapy drugs that can be used in children have expanded, but patients still face numerous side effects from the treatment. In addition, multidrug resistance (MDR) continues to pose a major challenge in improving the survival rates for a significant number of patients. This review focuses on the severe side effects of pediatric chemotherapy, including doxorubicin-induced cardiotoxicity (DIC) and vincristine-induced peripheral neuropathy (VIPN). We also delve into the mechanisms of MDR in chemotherapy to the improve survival and reduce the toxicity of treatment. Additionally, the review focuses on various drug transporters found in common types of pediatric tumors, which could offer different therapeutic options.
Precision Oncology: Evolving Clinical Trials across Tumor Types
Authors: Song I-Wen , Vo Henry Hiep , Chen Ying-Shiuan , Baysal Mehmet A. , Kahle Michael , Johnson Amber , Tsimberidou Apostolia M.
Published: March 2023

Advances in molecular technologies and targeted therapeutics have accelerated the implementation of precision oncology, resulting in improved clinical outcomes in selected patients. The use of next-generation sequencing and assessments of immune and other biomarkers helps optimize patient treatment selection. In this review, selected precision oncology trials including the IMPACT, SHIVA, IMPACT2, NCI-MPACT, TAPUR, DRUP, and NCI-MATCH studies are summarized, and their challenges and opportunities are discussed. Brief summaries of the new ComboMATCH, MyeloMATCH, and iMATCH studies, which follow the example of NCI-MATCH, are also included. Despite the progress made, precision oncology is inaccessible to many patients with cancer. Some patients’ tumors may not respond to these treatments, owing to the complexity of carcinogenesis, the use of ineffective therapies, or unknown mechanisms of tumor resistance to treatment. The implementation of artificial intelligence, machine learning, and bioinformatic analyses of complex multi-omic data may improve the accuracy of tumor characterization, and if used strategically with caution, may accelerate the implementation of precision medicine. Clinical trials in precision oncology continue to evolve, improving outcomes and expediting the identification of curative strategies for patients with cancer. Despite the existing challenges, significant progress has been made in the past twenty years, demonstrating the benefit of precision oncology in many patients with advanced cancer.
The Role of cMET in Gastric Cancer—A Review of the Literature
Authors: Van Herpe Filip , Van Cutsem Eric
Published: March 2023

Gastric cancer (GC) is an important cause of cancer worldwide with over one million new cases yearly. The vast majority of cases present in stage IV disease, and it still bears a poor prognosis. However, since 2010, progress has been made with the introduction of targeted therapies against HER2 and with checkpoint inhibitors (PDL1). More agents interfering with other targets (FGFR2B, CLDN18.2) are being investigated. cMET is a less frequent molecular target that has been studied for gastric cancer. It is a proto-oncogene that leads to activation of the MAPK pathway and the PI3K pathway, which is responsible for activating the MTOR pathway. The prevalence of cMET is strongly debated as different techniques are being used to detect MET-driven tumors. Because of the difference in diagnostic assays, selecting patients who benefit from cMET inhibitors is difficult. In this review, we discuss the pathway of cMET, its clinical significance and the different diagnostic assays that are currently used, such as immunohistochemy (IHC), fluorescence in situ hybridization (FISH), the H-score and next-generation sequencing (NGS). Next, we discuss all the current data on cMET inhibitors in gastric cancer. Since the data on cMET inhibitors are very heterogenous, it is difficult to provide a general consensus on the outcome, as inclusion criteria differ between trials. Diagnosing cMET-driven gastric tumors is difficult, and potentially the only accurate determination of cMET overexpression/amplification may be next-generation sequencing (NGS).
The Survival Outcomes, Prognostic Factors and Adverse Events following Systemic Chemotherapy Treatment in Bone Sarcomas: A Retrospective Observational Study from the Experience of the Cancer Referral Center in Northern Thailand
Authors: Sirikul Wachiranun , Buawangpong Nida , Pruksakorn Dumnoensun , Charoentum Chaiyut , Teeyakasem Pimpisa , Koonrungsesomboon Nut
Published: March 2023

This study aimed to assess survival outcomes, prognostic factors, and adverse events following chemotherapy treatment for osteosarcoma and Ewing’s sarcoma. This retrospective observational study was conducted to collect the data of the patients with osteosarcoma or Ewing’s sarcoma who received chemotherapy treatment between 2008 and 2019. The flexible parametric survival model was performed to explore the adjusted survival probability and the prognostic factors. A total of 102 patients (79 with osteosarcoma and 23 with Ewing’s sarcoma) were included. The estimated 5-year disease-free survival (DFS) and 5-year overall survival (OS) probabilities in patients with resectable disease were 60.9% and 63.3% for osteosarcoma, and 54.4% and 88.3% for Ewing’s sarcoma, respectively, whereas the 5-year DFS and 5-year OS for those with unresectable/metastatic disease remained below 25%. Two prognostic factors for osteosarcoma included a response to neoadjuvant chemotherapy and female gender. Ewing’s sarcoma patients aged 25 years and older were significantly associated with poorer survival outcomes. Of 181 chemotherapy treatment cycles, common self-reported adverse symptoms included tumor pain (n = 32, 17.7%), fever (n = 21, 11.6%), and fatigue (n = 16, 8.8%), while common grade III adverse events included febrile neutropenia (n = 13, 7.3%) and neutropenia (n = 9, 5.1%). There was no chemotherapy-related mortality (grade V) or anaphylaxis events.
Clinical Application of Small Extracellular Vesicles in Gynecologic Malignancy Treatments
Authors: Zheng Fei , Wang Jiao , Wang Dandan , Yang Qing
Published: March 2023

Small extracellular vesicles (sEVs) are the key mediators of intercellular communication. They have the potential for clinical use as diagnostic or therapeutic biomarkers and have been explored as vectors for drug delivery. Identification of reliable and noninvasive biomarkers, such as sEVs, is important for early diagnosis and precise treatment of gynecologic diseases to improve patient prognosis. Previous reviews have summarized routine sEVs isolation and identification methods; however, novel and unconventional methods have not been comprehensively described. This review summarizes a convenient method of isolating sEVs from body fluids and liquid biopsy-related sEV markers for early, minimally invasive diagnosis of gynecologic diseases. In addition, the characteristics of sEVs as drug carriers and in precision treatment and drug resistance are introduced, providing a strong foundation for identifying novel and potential therapeutic targets for sEV therapy. We propose potential directions for further research on the applications of sEVs in the diagnosis and treatment of gynecologic diseases.
Reprogramming of the Genome-Wide DNA Methylation Landscape in Three-Dimensional Cancer Cell Cultures
Authors: Heredia-Mendez Alma Jaqueline , Sánchez-Sánchez Gricelda , López-Camarillo César
Published: March 2023

During the last century, 2D cell cultures have been the tool most widely used to study cancer biology, drug discovery, genomics, and the regulation of gene expression at genetic/epigenetic levels. However, this experimental approach has limitations in faithfully recreating the microenvironment and cellular processes occurring in tumors. For these reasons, 3D cell cultures have recently been implemented to optimize the conditions that better recreate the biological and molecular features of tumors, including cell–cell and cell–extracellular matrix (ECM) interactions, growth kinetics, metabolic activities, and the development of gradients in the cellular microenvironment affecting the availability of oxygen and nutrients. In this sense, tumor cells receive stimuli from the local environment, resulting in significant changes in their signaling pathways, gene expression, and transcriptional and epigenetic patterns. In this review, we discuss how different types of 3D cell culture models can be applied to characterize the epigenetic footprints of cancer cell lines, emphasizing that DNA methylation patterns play an essential role in the emergence and development of cancer. However, how 3D cancer cell cultures remodel the epigenetic programs is poorly understood, with very few studies in this emerging topic. Here, we have summarized the studies on the reprogramming of the epigenetic landscape of DNA methylation during tumorigenesis and discuss how it may be affected by microenvironmental factors, specifically in 3D cell cultures.
Ceramide Synthase 1 Inhibits Brain Metastasis of Non-Small Cell Lung Cancer by Interacting with USP14 and Downregulating the PI3K/AKT/mTOR Signaling Pathway
Authors: Xu Yiquan , Pan Junfan , Lin Ying , Wu Yun , Chen Yusheng , Li Hongru
Published: March 2023

Brain metastasis (BM) is common in patients with non-small cell lung cancer (NSCLC) and is associated with a poor prognosis. Ceramide synthase 1 (CERS1) participates in malignancy development, but its potential role in NSCLC BM remains unclear. This study aimed to explore the physiological effects and molecular mechanism of CERS1 in NSCLC BM. CERS1 expression was evaluated in NSCLC tissues and cell lines, and its physiological roles were subsequently explored in vivo and in vitro. Mass spectrometry and co-immunoprecipitation were performed to explore CERS1-interacting proteins. The associated signaling pathways of CERS1 in NSCLC BM were further investigated using bioinformatics analysis and molecular biotechnology. We demonstrated that CERS1 was significantly downregulated in NSCLC cell lines and BM tissues, and its upregulation was associated with better prognoses. In vitro, CERS1 overexpression inhibited cell migration, invasion, and the ability to penetrate the blood-brain barrier. Moreover, CERS1 interacted with ubiquitin-specific protease 14 (USP14) and inhibited BM progression by downregulating the PI3K/AKT/mTOR signaling pathway. Further, CERS1 expression substantially suppressed BM tumor formation in vivo. This study demonstrated that CERS1 plays a suppressor role in NSCLC BM by interacting with USP14 and downregulating the PI3K/AKT/mTOR signaling pathway, thereby serving as a novel therapeutic target for NSCLC BM.
Activin and BMP Signalling in Human Testicular Cancer Cell Lines, and a Role for the Nucleocytoplasmic Transport Protein Importin-5 in Their Crosstalk
Authors: Radhakrishnan Karthika , Luu Michael , Iaria Josie , Sutherland Jessie M. , McLaughlin Eileen A. , Zhu Hong-Jian , Loveland Kate L.
Published: March 2023

Testicular germ cell tumours (TGCTs) are the most common malignancy in young men. Originating from foetal testicular germ cells that fail to differentiate correctly, TGCTs appear after puberty as germ cell neoplasia in situ cells that transform through unknown mechanisms into distinct seminoma and non-seminoma tumour types. A balance between activin and BMP signalling may influence TGCT emergence and progression, and we investigated this using human cell line models of seminoma (TCam-2) and non-seminoma (NT2/D1). Activin A- and BMP4-regulated transcripts measured at 6 h post-treatment by RNA-sequencing revealed fewer altered transcripts in TCam-2 cells but a greater responsiveness to activin A, while BMP4 altered more transcripts in NT2/D1 cells. Activin significantly elevated transcripts linked to pluripotency, cancer, TGF-β, Notch, p53, and Hippo signalling in both lines, whereas BMP4 altered TGF-β, pluripotency, Hippo and Wnt signalling components. Dose-dependent antagonism of BMP4 signalling by activin A in TCam-2 cells demonstrated signalling crosstalk between these two TGF-β superfamily arms. Levels of the nuclear transport protein, IPO5, implicated in BMP4 and WNT signalling, are highly regulated in the foetal mouse germline. IPO5 knockdown in TCam-2 cells using siRNA blunted BMP4-induced transcript changes, indicating that IPO5 levels could determine TGF-β signalling pathway outcomes in TGCTs.
Effect of the Metabotropic Glutamate Receptor Type 5 Negative Allosteric Modulator Dipraglurant on Motor and Non-Motor Symptoms of Parkinson’s Disease
Authors: Epping-Jordan Mark P. , Girard Françoise , Bessis Anne-Sophie , Mutel Vincent , Boléa Christelle , Derouet Francis , Bessif Abdelhak , Mingard Brice , Barbier Stéphanie , Paradis Justine S. , Rocher Jean-Philippe , Lütjens Robert , Kalinichev Mikhail , Poli Sonia
Published: March 2023

Parkinson’s disease (PD) patients suffer not only from the primary motor symptoms of the disease but also from a range of non-motor symptoms (NMS) that cause disability and low quality of life. Excessive glutamate activity in the basal ganglia resulting from degeneration of the nigrostriatal dopamine pathway has been implicated in the motor symptoms, NMS and dyskinesias in PD patients. In this study, we investigated the effects of a selective mGlu5 negative allosteric modulator (NAM), dipraglurant, in a rodent motor symptoms model of PD, but also in models of anxiety, depression and obsessive-compulsive disorder, all of which are among the most prevalent NMS symptoms. Dipraglurant is rapidly absorbed after oral administration, readily crosses the blood-brain barrier, and exhibits a high correlation between plasma concentration and efficacy in behavioral models. In vivo, dipraglurant dose-dependently reduced haloperidol-induced catalepsy, increased punished licks in the Vogel conflict-drinking model, decreased immobility time in the forced swim test, decreased the number of buried marbles in the marble-burying test, but had no effect on rotarod performance or locomotor activity. These findings suggest that dipraglurant may have benefits to address some of the highly problematic comorbid non-motor symptoms of PD, in addition to its antidyskinetic effect demonstrated in PD-LID patients.