bluuebunny/crossref_metadata_2025 huggingface dataset:
Online Voting Scheme Using IBM Cloud-Based Hyperledger Fabric with Privacy-Preservation
Authors: Clarke Ross , McGuire Luke , Baza Mohamed , Rasheed Amar , Alsabaan Maazen
Published: July 2023

The current traditional paper ballot voting schemes suffer from several limitations such as processing delays due to counting paper ballots, lack of transparency, and manipulation of the ballots. To solve these limitations, an electronic voting (e-voting) scheme has received massive interest from both governments and academia. In e-voting, individuals can cast their vote online using their smartphones without the need to wait in long lines. Additionally, handicapped voters who face limited wheelchair access in many polling centers could now participate in elections hassle-free. The existing e-voting schemes suffer from several limitations as they are either centralized, based on public blockchains, or utilize local private blockchains. This results in privacy issues (using public blockchains) or large financial costs (using local/private blockchains) due to the amount of computing power and technical knowledge needed to host blockchains locally. To address the aforementioned limitations, in this paper, we propose an online voting scheme using IBM cloud-based Hyperledger Fabric. Our scheme allows voters to cast their encrypted votes in a secure manner. Then any participant can obtain the ballot results in a decentralized and transparent manner, without sacrificing the privacy of individual voters. We implement the proposed scheme using IBM cloud-based Hyperledger Fabric. The experimental results identify the performance characteristics of our scheme and demonstrate that it is feasible to run an election consisting of thousands of participants using cloud-based Fabric.
Patterns and Drivers of Change in the Normalized Difference Vegetation Index in Nunavik (Québec, Canada) over the Period 1984–2020
Authors: Gaspard Anna , Simard Martin , Boudreau Stéphane
Published: July 2023

Altered temperature and precipitation regimes associated with climate change generally result in improved conditions for plant growth. For Arctic and sub-Arctic ecosystems, this new climatic context promotes an increase in primary productivity, a phenomenon often referred to as “greening”. Although this phenomenon has been widely documented at the circumpolar scale, little information is available at the scale of plant communities, the basic unit of the Arctic and sub-Arctic landscape mosaic. The objectives of this study were (1) to quantify the variation of NDVI within the different plant communities of Nunavik (Québec, QC, Canada) in order to identify which ones contributed the most to the greening and (2) to identify the climatic and biophysical drivers of the greening. To do so, we used Landsat imagery to produce a time series of summer NDVI for the period 1984 to 2020. A fine-resolution map of Northern Québec vegetation was then overlaid on the time series of NDVI imagery and on maps of surficial deposits, topography, and gridded climate data to obtain information at the plant community level. We found that greening was more important in shrub-dominated communities, particularly near the tree line. Summer temperature, fall and winter precipitation, and surficial deposits were identified as drivers of greening. Through utilizing detailed vegetation maps to accurately quantify changes in Nunavik’s plant communities, this study provides valuable insights into the dynamics of the region’s ecosystem under rapid climate change.
Composition, Distribution, and Attribution of Hydrochemistry in Drainage Systems in the North of Tianshan Mountains, China
Authors: Zhang Jia-Xin , Zhu Bing-Qi
Published: July 2023

The characteristics and sources of the hydrochemical composition of natural water are mainly influenced and limited at the basin scale by what factors, this has become a focal issue of environmental change in the middle latitude areas and even globally. In this study, three large drainage systems (Junggar, Yili, and Erlqis) in the north of the Tianshan Mountains were selected to study the hydrochemistry of different river basins and understand the relevant causes and attributions of different water bodies in arid environments in the Central Asian Orogenic Belt (CAOB). Natural water samples from the three drainage systems and their hydrochemical data, combined with literature data of the north and south Tianshan Mountains and surrounding areas, were systematically collected and comprehensively compared with other higher, middle, and low latitude watersheds with different climate conditions. The results show that the total dissolved solid concentrations in the CAOB drainage systems are generally higher than those of rivers in Chinese monsoon and humid regions, and also higher than the world average level. The relative concentrations of different ions are similar to those of rivers in the monsoon region of eastern China and most rivers in the world dominated by carbonate weathering. The ionic compositions of surface water bodies from different sub-basins in the study area are distributed near the Ca apex in the piper diagram, while those of phreatic and confined groundwater samples tend to the Na apex. The compositional differences in the anions are not like those in the cations, rarely distinguishable for these different water types. In a sub-drainage basin scale from I to VIII sub-basins in the study area, major ion concentrations and distributions in these basins are evidently heterogeneous. Almost all the cation and anion concentrations span > 1 order of magnitude, especially sodium and chlorine; however, the calcium and alkalinity concentrations and distributions are relatively homogeneous for some basins in the Junggar and Yili drainage systems. The relative homogeneity between anions and the relative heterogeneity between cations can be recognized in the ion chemistry of natural water samples between different types, indicating that the composition and distribution of cations in water is more conducive than those of anions to identifying the differences and commonalities between different regions. Atmospheric precipitation plays a key role on the hydrogeochemical process in the north of the Tianshan Mountains, and the elevation differentiation of chemical weathering and ion concentrations are closely related to it. The positive correlation between total solute flux and runoff cannot be explained by the dilution effect, indicating that hydroclimatic factors such as runoff and aridity have a strong effect in limiting the hydrochemistry of natural water bodies in the study area.
Tracking the Convection Potential Based on a Foundation Remote Sensing Air Sounding Profile System
Authors: Lin Xiaomeng , Chen Hong , Zhang Nan , Wei Yinghua , Liu Yiwei , Wang Yanchun
Published: July 2023

Using ground-based remote sensing equipment (wind profile radar and microwave radiometer) data and ground automatic station data, a ground-based remote sensing sounding profile system (FAS) is constructed, which aims to make use of its advantages of high resolution, high accuracy, and low cost to make up for the lack of space–time density in existing conventional sounding layer information. The retrieval results of remote sensing sounding profiles in Beijing from May 2021 to September 2022 were tested and evaluated. The results show that the correlation coefficient between FAS and conventional sounding specific humidity is 0.89, the root–mean–square deviation is 1.53 g/kg, and the evolution trends of different data sources of convective available potential energy (CAPE) and vertical wind shear are synchronous. A case study was conducted to evaluate the effectiveness of 40 severe convective processes in the Beijing Plain area. The results show that, due to the minute-level time resolution of FAS, the retrieved convective parameters could track the evolution trend of the atmospheric state with high timeliness, dynamically describe the configuration of thermodynamic parameters, and indicate the time-varying local convective potential and instability level. Therefore, it has certain short-term forecasting significance for the occurrence time, intensity, and convection type.
Exploring the Immunomodulatory Properties of Stem Cells in Combating COVID-19: Can We Expect More?
Authors: Mallis Panagiotis
Published: July 2023

Since the first appearance of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) in December 2019, the disease has displayed a remarkable interindividual variability in the global population, resulting in different mortality and morbidity rates. Still, an effective cure against SARS-CoV-2 has not been developed, and therefore, alternative therapeutic protocols must also be evaluated. Considering that stem cells, especially Mesenchymal Stromal Cells (MSCs), are characterized by both regenerative and immunomodulatory properties and that their safety and tolerability have been investigated previously, these cells could potentially be applied against coronavirus disease 19 (COVID-19). In addition, an individual’s genetic background is further related to disease pathogenesis, especially rare Inborn Errors of Immunity (IEIs), autoantibodies against Interferon type I, and the presence of different Human Leukocyte Antigens (HLA) alleles, which are actively associated with protection or susceptibility in relation to SARS-CoV-2. Herein, the use of MSCs as a potential stem cell therapy will require a deep understanding of their immunomodulatory properties associated with their HLA alleles. In such a way, HLA-restricted MSC lines can be developed and applied precisely, offering more solutions to clinicians in attenuating the mortality of SARS-CoV-2.
Semantic Segmentation of Gastric Polyps in Endoscopic Images Based on Convolutional Neural Networks and an Integrated Evaluation Approach
Authors: Yan Tao , Qin Ye Ying , Wong Pak Kin , Ren Hao , Wong Chi Hong , Yao Liang , Hu Ying , Chan Cheok I , Gao Shan , Chan Pui Pun
Published: July 2023

Convolutional neural networks (CNNs) have received increased attention in endoscopic images due to their outstanding advantages. Clinically, some gastric polyps are related to gastric cancer, and accurate identification and timely removal are critical. CNN-based semantic segmentation can delineate each polyp region precisely, which is beneficial to endoscopists in the diagnosis and treatment of gastric polyps. At present, just a few studies have used CNN to automatically diagnose gastric polyps, and studies on their semantic segmentation are lacking. Therefore, we contribute pioneering research on gastric polyp segmentation in endoscopic images based on CNN. Seven classical semantic segmentation models, including U-Net, UNet++, DeepLabv3, DeepLabv3+, Pyramid Attention Network (PAN), LinkNet, and Muti-scale Attention Net (MA-Net), with the encoders of ResNet50, MobineNetV2, or EfficientNet-B1, are constructed and compared based on the collected dataset. The integrated evaluation approach to ascertaining the optimal CNN model combining both subjective considerations and objective information is proposed since the selection from several CNN models is difficult in a complex problem with conflicting multiple criteria. UNet++ with the MobineNet v2 encoder obtains the best scores in the proposed integrated evaluation method and is selected to build the automated polyp-segmentation system. This study discovered that the semantic segmentation model has a high clinical value in the diagnosis of gastric polyps, and the integrated evaluation approach can provide an impartial and objective tool for the selection of numerous models. Our study can further advance the development of endoscopic gastrointestinal disease identification techniques, and the proposed evaluation technique has implications for mathematical model-based selection methods for clinical technologies.
Performance Comparison of Object Detection Networks for Shrapnel Identification in Ultrasound Images
Authors: Hernandez-Torres Sofia I. , Hennessey Ryan P. , Snider Eric J.
Published: July 2023

Ultrasound imaging is a critical tool for triaging and diagnosing subjects but only if images can be properly interpreted. Unfortunately, in remote or military medicine situations, the expertise to interpret images can be lacking. Machine-learning image interpretation models that are explainable to the end user and deployable in real time with ultrasound equipment have the potential to solve this problem. We have previously shown how a YOLOv3 (You Only Look Once) object detection algorithm can be used for tracking shrapnel, artery, vein, and nerve fiber bundle features in a tissue phantom. However, real-time implementation of an object detection model requires optimizing model inference time. Here, we compare the performance of five different object detection deep-learning models with varying architectures and trainable parameters to determine which model is most suitable for this shrapnel-tracking ultrasound image application. We used a dataset of more than 16,000 ultrasound images from gelatin tissue phantoms containing artery, vein, nerve fiber, and shrapnel features for training and evaluating each model. Every object detection model surpassed 0.85 mean average precision except for the detection transformer model. Overall, the YOLOv7tiny model had the higher mean average precision and quickest inference time, making it the obvious model choice for this ultrasound imaging application. Other object detection models were overfitting the data as was determined by lower testing performance compared with higher training performance. In summary, the YOLOv7tiny object detection model had the best mean average precision and inference time and was selected as optimal for this application. Next steps will implement this object detection algorithm for real-time applications, an important next step in translating AI models for emergency and military medicine.
Model-Based Characterization of E. coli Strains with Impaired Glucose Uptake
Authors: Krausch Niels , Kaspersetz Lucas , Gaytán-Castro Rogelio Diego , Schermeyer Marie-Therese , Lara Alvaro R. , Gosset Guillermo , Cruz Bournazou Mariano Nicolas , Neubauer Peter
Published: July 2023

The bacterium Escherichia coli is a widely used organism in biotechnology. For high space-time yields, glucose-limited fed-batch technology is the industry standard; this is because an overflow metabolism of acetate occurs at high glucose concentrations. As an interesting alternative, various strains with limited glucose uptake have been developed. However, these have not yet been characterized under process conditions. To demonstrate the efficiency of our previously developed high-throughput robotic platform, in the present work, we characterized three different exemplary E. coli knockout (KO) strains with limited glucose uptake capacities at three different scales (microtiter plates, 10 mL bioreactor system and 100 mL bioreactor system) under excess glucose conditions with different initial glucose concentrations. The extensive measurements of growth behavior, substrate consumption, respiration, and overflow metabolism were then used to determine the appropriate growth parameters using a mechanistic mathematical model, which allowed for a comprehensive comparative analysis of the strains. The analysis was performed coherently with these different reactor configurations and the results could be successfully transferred from one platform to another. Single and double KO mutants showed reduced specific rates for substrate uptake qSmax and acetate production qApmax; meanwhile, higher glucose concentrations had adverse effects on the biomass yield coefficient YXSem. Additional parameters compared to previous studies for the oxygen uptake rate and carbon dioxide production rate indicated differences in the specific oxygen uptake rate qOmax. This study is an example of how automated robotic equipment, together with mathematical model-based approaches, can be successfully used to characterize strains and obtain comprehensive information more quickly, with a trade-off between throughput and analytical capacity.
Xanthine–Dopamine Hybrid Molecules as Multitarget Drugs with Potential for the Treatment of Neurodegenerative Diseases
Authors: Załuski Michał , Karcz Tadeusz , Drabczyńska Anna , Vielmuth Christin , Olejarz-Maciej Agnieszka , Głuch-Lutwin Monika , Mordyl Barbara , Siwek Agata , Satała Grzegorz , Müller Christa E. , Kieć-Kononowicz Katarzyna
Published: July 2023

Multitarget drugs based on a hybrid dopamine–xanthine core were designed as potential drug candidates for the treatment of neurodegenerative diseases. Monoamine oxidase B (MAO-B) inhibitors with significant ancillary A2A adenosine receptor (A2AAR) antagonistic properties were further developed to exhibit additional phosphodiesterase-4 and -10 (PDE4/10) inhibition and/or dopamine D2 receptor (D2R) agonistic activity. While all of the designed compounds showed MAO-B inhibition in the nanomolar range mostly combined with submicromolar A2AAR affinity, significant enhancement of PDE-inhibitory and D2R-agonistic activity was additionally reached for some compounds through various structural modifications. The final multitarget drugs also showed promising antioxidant properties in vitro. In order to evaluate their potential neuroprotective effect, representative ligands were tested in a cellular model of toxin-induced neurotoxicity. As a result, protective effects against oxidative stress in neuroblastoma cells were observed, confirming the utility of the applied strategy. Further evaluation of the newly developed multitarget ligands in preclinical models of Alzheimer’s and Parkinson’s diseases is warranted.
Systems Biology and Omics Approaches for Complex Human Diseases
Authors: Selvarajoo Kumar , Giuliani Alessandro
Published: July 2023

For many years, there has been general interest in developing virtual cells or digital twin models [...]
COVID-19 and HIV: Clinical Outcomes among Hospitalized Patients in the United States
Authors: Faiz Zohaa , Quazi Mohammed A. , Vahil Neel , Barrows Charles M. , Ikram Hafiz Abdullah , Nasrullah Adeel , Farooq Asif , Gangu Karthik , Sheikh Abu Baker
Published: July 2023

The concurrence of HIV and COVID-19 yields unique challenges and considerations for healthcare providers, patients living with HIV, and healthcare systems at-large. Persons living with HIV may face a higher risk of acquiring SARS-CoV-2 infection and experiencing worse clinical outcomes compared to those without. Notably, COVID-19 may have a disproportionate impact on historically disadvantaged populations, including African Americans and those stratified in a lower socio-economic status. Using the National Inpatient Sample (NIS) database, we compared patients with a diagnosis of both HIV and COVID-19 and those who exclusively had a diagnosis of COVID-19. The primary outcome was in-hospital mortality. Secondary outcomes were intubation rate and vasopressor use; acute MI, acute kidney injury (AKI); AKI requiring hemodialysis (HD); venous thromboembolism (VTE); septic shock and cardiac arrest; length of stay; financial burden on healthcare; and resource utilization. A total of 1,572,815 patients were included in this study; a COVID-19-positive sample that did not have HIV (n = 1,564,875, 99.4%) and another sample with HIV and COVID-19 (n = 7940, 0.56%). Patients with COVID-19 and HIV did not have a significant difference in mortality compared to COVID-19 alone (10.2% vs. 11.3%, respectively, p = 0.35); however, that patient cohort did have a significantly higher rate of AKI (33.6% vs. 28.6%, aOR: 1.26 [95% CI 1.13–1.41], p < 0.001). Given the complex interplay between HIV and COVID-19, more prospective studies investigating the factors such as the contribution of viral burden, CD4 cell count, and the details of patients’ anti-retroviral therapeutic regimens should be pursued.
Validating Prediction Tools for Autoimmune Encephalitis in Adult Taiwanese Patients: A Retrospective Study
Authors: Lu Yan-Ting , Lin Chih-Hsiang , Ho Chen-Jui , Chen Shih-Ying , Tsai Meng-Han
Published: July 2023

Autoimmune encephalitis (AE) is a neurological emergency. We aimed to analyze the application and effectiveness of the currently available prediction tools for AE patients in Taiwan. We retrospectively collected 27 AE patients between January 2008 and December 2019. Antibody Prevalence in Epilepsy (APE) score, Response to Immunotherapy in Epilepsy (RITE) score, and anti-NMDAR Encephalitis One Year Functional Status (NEOS) score were applied to validate their usability. Based on the defined cutoff values, the sensitivity and specificity of each score were calculated. A receiver operating characteristic (ROC) curve and the area under the curve (AUC) were generated for each scoring system. The AUC value of APE was 0.571. The AUC value of RITE was 0.550. The AUC values for the NEOS score at discharge and long-term follow-up were 0.645 and 0.796, respectively. The performance of APE and RITE scores was suboptimal in the Taiwanese cohort, probably due to the limitations of the small sample size and single ethnicity. On the other hand, the NEOS score performed better on long-term follow-up than at discharge.
NJN: A Dataset for the Normal and Jaundiced Newborns
Authors: Abdulrazzak Ahmad Yaseen , Mohammed Saleem Latif , Al-Naji Ali
Published: July 2023

Neonatal jaundice is a prevalent condition among newborns, with potentially severe complications that can result in permanent brain damage if left untreated during its early stages. The existing approaches for jaundice detection involve invasive procedures such as blood sample collection, which can inflict pain and distress on the patient, and may give rise to additional complications. Alternatively, a non-invasive method using image-processing techniques and implementing kNN, Random Forest, and XGBoost machine learning algorithms as a classifier can be employed to diagnose jaundice, necessitating a comprehensive database of infant images to achieve a diagnosis with high accuracy. This data article presents the NJN collection, a repository of newborn images encompassing diverse birthweights and skin tones, spanning an age range of 2 to 8 days. The dataset is accompanied by an Excel sheet file in CSV format containing the RGB and YCrCb channel values, as well as the status of each sample. The dataset and associated resources are openly accessible at Zenodo website. Moreover, the Python code for data testing utilizing various AI techniques is provided. Consequently, this article offers an unparalleled resource for AI researchers, enabling them to train their AI systems and develop algorithms that can assist neonatal intensive care unit (NICU) healthcare specialists in monitoring neonates while facilitating the fast, real-time, non-invasive, and accurate diagnosis of jaundice.
Reflection-Boosted Wearable Ring-Type Pulse Oximeters for SpO2 Measurement with High Sensitivity and Low Power Consumption
Authors: Joo Min Gyu , Lim Dae Hyeong , Park Kyu-Kwan , Baek Jiwon , Choi Jong Min , Baac Hyoung Won
Published: July 2023

In this study, we demonstrated a Monte Carlo simulation to model a finger structure and to calculate the intensity of photons passing through tissues, in order to determine optimal angular separation between a photodetector (PD) and a light-emitting diode (LED), to detect SpO2. Furthermore, our model was used to suggest a mirror-coated ring-type pulse oximeter to improve the sensitivity by up to 80% and improve power consumption by up to 65% compared to the mirror-uncoated structure. A ring-type pulse oximeter (RPO) is widely used to detect photoplethysmography (PPG) signals for SpO2 measurement during sleep and health-status monitoring. Device sensitivity and the power consumption of an RPO, which are key performance indicators, vary greatly with the geometrical arrangement of PD and LED within the inner surface of an RPO. We propose a reflection-boosted design of an RPO to achieve both high sensitivity and low power consumption, and determine an optimal configuration of a PD and LED by performing a 3D Monte Carlo simulation and confirming its agreement with experimental measurement. In order to confirm the reflection-boosted performance in terms of signal-to-noise ratio, R ratio, and perfusion index (PI), RPOs were fabricated with and without a highly reflective coating, and then used for SpO2 measurement from eight participants. Our simulation allows the numerical calculation of the intensity of photon passing and scattering through finger tissues. The reflection-boosted RPO enables reliable measurement with high sensitivity, resulting in less power consumption for the LED and longer device usage than conventional RPOs without any reflective coating, in order to maintain the same level of SNR and PI. Compared to the non-reflective reference RPO, the reflection-boosted RPO design greatly enhanced both detected light intensity (67% in dc and 322% in ac signals at a wavelength λ1 = 660 nm, and also 81% and 375% at λ2 = 940 nm, respectively) and PI (23.3% at λ1 and 25.5% at λ2). Thus, the reflection-boosted design not only enhanced measurement reliability but also significantly improved power consumption, i.e., by requiring only 36% and 30% power to drive the LED sources with λ1 and λ2, respectively, to produce the device performance of a non-reflective RPO reference. It is expected that our proposed RPO provides long-term monitoring capability with low power consumption and an enhanced PI for SpO2 measurement.
Experimental Behavior of High-Strength Concrete Reinforced with Aramid Fiber and Polyurethane Resin
Authors: Amalraj Edwin Fernando Packianathan , Ilangovan Padmanaban
Published: July 2023

Over the past few decades, research has been conducted to develop high-strength concrete (HSC) for high-rise structures and bridge decks. The research discussed in the study focuses on using polyurethane resin (PR) and aramid fibers (AF) to develop HSC, which enhances its strength, durability, and structural properties without increasing the cementitious content. This approach can lead to more sustainable and cost-effective construction practices by reducing the cementitious materials required. In the present investigation, M50-grade concrete mixes were designed in accordance with the guidelines mentioned in Indian Standard (IS) 10262 along with the addition of supplementary cementitious materials, such as fly ash and silica fume. Initially, varying percentages of AF (0% to 3%) and PR (0% to 6%) were added into the concrete mixes and detailed experimental investigations were completed on workability, strength, durability, and structural properties. It is concluded that the addition of AF and PR shows significant improvements in strength, durability, and structural properties compared to traditional HSC created with zero AF and PR content. As reinforced concrete (RC) elements serve as the final product for human construction projects, it is crucial to ensure that their structural properties are reliable. In order to validate the findings from experimental investigations, numerical simulations were conducted using the ANSYS commercial package software. Specifically, the structural properties of RC beams were analyzed using this software, allowing for further validation and verification of the experimental results. From the detailed investigation, it is concluded that 2.5% addition of AF and 4% addition of PR demonstrates better results and is considered the optimum ingredient dosage, which can be used as a reference for future studies and practical applications. These findings can result in the development of new and improved building materials and techniques that can potentially lead to safer, more durable, and sustainable structures.
Earthquake Economic Loss Assessment of Reinforced Concrete Structures Using Multiple Response Variables
Authors: Liu Xiaoxiao , Chen Jingming , Wang Hongchen , Jia Zhaoping , Wu Ziyan
Published: July 2023

For buildings that meet the requirements of current seismic design codes, damage to nonstructural components and the internal objects of buildings often become the main source of the seismic economic losses of these buildings. However, the current specifications only consider the safety of ‘no collapse under strong earthquake’ and do not consider ‘functional recoverability’. In this paper, a six-story frame building was taken as an example. Four joint performance limit states were proposed, as per FEMA 273, to establish a two-dimensional probabilistic seismic demand model that considers parameter correlations. The limit state function was established, and the two-dimensional seismic vulnerability curve was calculated. The seismic intensity–economic loss curve and the annual average economic loss established by one-dimensional and two-dimensional seismic vulnerability curves were compared. The results showed that the seismic performance of the structure was lower than expected when using only a one-dimensional seismic vulnerability curve. However, the situation was more serious under high-intensity earthquake and high-performance levels.
Three-Dimensional Breast Cancer Model to Investigate CCL5/CCR1 Expression Mediated by Direct Contact between Breast Cancer Cells and Adipose-Derived Stromal Cells or Adipocytes
Authors: Watzling Martin , Klaus Lorenz , Weidemeier Tamara , Horder Hannes , Ebert Regina , Blunk Torsten , Bauer-Kreisel Petra
Published: July 2023

The tumor microenvironment (TME) in breast cancer is determined by the complex crosstalk of cancer cells with adipose tissue-inherent cells such as adipose-derived stromal cells (ASCs) and adipocytes resulting from the local invasion of tumor cells in the mammary fat pad. This leads to heterotypic cellular contacts between these cell types. To adequately mimic the specific cell-to-cell interaction in an in vivo-like 3D environment, we developed a direct co-culture spheroid model using ASCs or differentiated adipocytes in combination with MDA-MB-231 or MCF-7 breast carcinoma cells. Co-spheroids were generated in a well-defined and reproducible manner in a high-throughput process. We compared the expression of the tumor-promoting chemokine CCL5 and its cognate receptors in these co-spheroids to indirect and direct standard 2D co-cultures. A marked up-regulation of CCL5 and in particular the receptor CCR1 with strict dependence on cell–cell contacts and culture dimensionality was evident. Furthermore, the impact of direct contacts between ASCs and tumor cells and the involvement of CCR1 in promoting tumor cell migration were demonstrated. Overall, these results show the importance of direct 3D co-culture models to better represent the complex tumor–stroma interaction in a tissue-like context. The unveiling of tumor-specific markers that are up-regulated upon direct cell–cell contact with neighboring stromal cells, as demonstrated in the 3D co-culture spheroids, may represent a promising strategy to find new targets for the diagnosis and treatment of invasive breast cancer.
Targeting Transcription Factor YY1 for Cancer Treatment: Current Strategies and Future Directions
Authors: Hosea Rendy , Hillary Sharon , Wu Shourong , Kasim Vivi
Published: July 2023

Cancer represents a significant and persistent global health burden, with its impact underscored by its prevalence and devastating consequences. Whereas numerous oncogenes could contribute to cancer development, a group of transcription factors (TFs) are overactive in the majority of tumors. Targeting these TFs may also combat the downstream oncogenes activated by the TFs, making them attractive potential targets for effective antitumor therapeutic strategy. One such TF is yin yang 1 (YY1), which plays crucial roles in the development and progression of various tumors. In preclinical studies, YY1 inhibition has shown efficacy in inhibiting tumor growth, promoting apoptosis, and sensitizing tumor cells to chemotherapy. Recent studies have also revealed the potential of combining YY1 inhibition with immunotherapy for enhanced antitumor effects. However, clinical translation of YY1-targeted therapy still faces challenges in drug specificity and delivery. This review provides an overview of YY1 biology, its role in tumor development and progression, as well as the strategies explored for YY1-targeted therapy, with a focus on their clinical implications, including those using small molecule inhibitors, RNA interference, and gene editing techniques. Finally, we discuss the challenges and current limitations of targeting YY1 and the need for further research in this area.
Early Onset Metastatic Colorectal Cancer: Current Insights and Clinical Management of a Rising Condition
Authors: Medici Bianca , Riccò Beatrice , Caffari Eugenia , Zaniboni Silvia , Salati Massimiliano , Spallanzani Andrea , Garajovà Ingrid , Benatti Stefania , Chiavelli Chiara , Dominici Massimo , Gelsomino Fabio
Published: July 2023

Despite a recent overall decrease in colorectal cancer (CRC) incidence and mortality, there has been a significant rise in CRC diagnoses in young adults. Early onset colorectal cancer (EOCRC) is defined as CRC diagnosed before the age of 50. Possible predisposing conditions include not only genetic syndromes but also other risk factors, such as microbiome alteration, antibiotic exposure, obesity, diabetes mellitus, and inflammatory bowel disease. EOCRC tends to be diagnosed later than in the older counterpart because of a lack of awareness and the fact that screening for CRC usually starts at the age of 50. Furthermore, CRC in young adults seems to be related to unique molecular features and more aggressive clinical behavior. This paper aims to provide an in-depth review of this poorly understood subject, with a comprehensive review of the state of the art and considerations for future perspectives.
Astroglial Cell-to-Cell Interaction with Autoreactive Immune Cells in Experimental Autoimmune Encephalomyelitis Involves P2X7 Receptor, β3-Integrin, and Connexin-43
Authors: Milicevic Katarina D. , Bataveljic Danijela B. , Bogdanovic Pristov Jelena J. , Andjus Pavle R. , Nikolic Ljiljana M.
Published: July 2023

In multiple sclerosis (MS), glial cells astrocytes interact with the autoreactive immune cells that attack the central nervous system (CNS), which causes and sustains neuroinflammation. However, little is known about the direct interaction between these cells when they are in close proximity in the inflamed CNS. By using an experimental autoimmune encephalomyelitis (EAE) model of MS, we previously found that in the proximity of autoreactive CNS-infiltrated immune cells (CNS-IICs), astrocytes respond with a rapid calcium increase that is mediated by the autocrine P2X7 receptor (P2X7R) activation. We now reveal that the mechanisms regulating this direct interaction of astrocytes and CNS-IICs involve the coupling between P2X7R, connexin-43, and β3-integrin. We found that P2X7R and astroglial connexin-43 interact and concentrate in the immediate proximity of the CNS-IICs in EAE. P2X7R also interacts with β3-integrin, and the block of astroglial αvβ3-integrin reduces the P2X7R-dependent calcium response of astrocytes upon encountering CNS-IICs. This interaction was dependent on astroglial mitochondrial activity, which regulated the ATP-driven P2X7R activation and facilitated the termination of the astrocytic calcium response evoked by CNS-IICs. By further defining the interactions between the CNS and the immune system, our findings provide a novel perspective toward expanding integrin-targeting therapeutic approaches for MS treatment by controlling the cell–cell interactions between astrocytes and CNS-IICs.
Interplay between Protein Kinase C Epsilon and Reactive Oxygen Species during Myogenic Differentiation
Authors: Pozzi Giulia , Presta Valentina , Masselli Elena , Condello Giancarlo , Cortellazzi Samuele , Arcari Maria Luisa , Micheloni Cristina , Vitale Marco , Gobbi Giuliana , Mirandola Prisco , Carubbi Cecilia
Published: July 2023

Reactive oxygen species (ROS) are currently recognized as a key driver of several physiological processes. Increasing evidence indicates that ROS levels can affect myogenic differentiation, but the molecular mechanisms still need to be elucidated. Protein kinase C (PKC) epsilon (PKCe) promotes muscle stem cell differentiation and regeneration of skeletal muscle after injury. PKCs play a tissue-specific role in redox biology, with specific isoforms being both a target of ROS and an up-stream regulator of ROS production. Therefore, we hypothesized that PKCe represents a molecular link between redox homeostasis and myogenic differentiation. We used an in vitro model of a mouse myoblast cell line (C2C12) to study the PKC–redox axis. We demonstrated that the transition from a myoblast to myotube is typified by increased PKCe protein content and decreased ROS. Intriguingly, the expression of the antioxidant enzyme superoxide dismutase 2 (SOD2) is significantly higher in the late phases of myogenic differentiation, mimicking PKCe protein content. Furthermore, we demonstrated that PKCe inhibition increases ROS and reduces SOD2 protein content while SOD2 silencing did not affect PKCe protein content, suggesting that the kinase could be an up-stream regulator of SOD2. To support this hypothesis, we found that in C2C12 cells, PKCe interacts with Nrf2, whose activation induces SOD2 transcription. Overall, our results indicate that PKCe is capable of activating the antioxidant signaling preventing ROS accumulation in a myotube, eventually promoting myogenic differentiation.
Materials in the CaO-K2O-SO3-H2O System Based on Powder Mixtures including Calciolangbeinite K2Ca2(SO4)3 and Calcium Sulfate Anhydrite CaSO4
Authors: Kuznetsov Alexander I. , Safronova Tatiana V. , Shatalova Tatiana B. , Filippov Yaroslav Y. ,   Leonid A. Vaymugin, Vlasenko Vyacheslav S. , Likhanov Maxim S.
Published: July 2023

Materials (cement stone samples) in the CaO-K2O-SO3-H2O system with the target phase compositions, including syngenite K2Ca(SO4)2·H2O and calcium sulfate dihydrate CaSO4·2H2O, were prepared from powder mixtures of calcium sulfate anhydrite CaSO4, and/or calciolangbeinite K2Ca2(SO4)3, and potassium sulfate K2SO4 via hydration reactions at a water/powder ratio within an interval of 0.5–0.9. It was revealed that samples with contents of 25, 50, 75 and 100 mol% of syngenite K2Ca(SO4)2·H2O demonstrated a nonlinear dependence of their respective microstructures on their phase compositions. The microstructures of samples with phase compositions of 25 and 75 mol% of syngenite K2Ca(SO4)2·H2O consisted of pillar crystals. The microstructures of samples with phase compositions of 50 and 100 mol% of syngenite K2Ca(SO4)2·H2O consisted of plate crystals. An explanation of microstructure formation was set forth, taking into account equilibria of the dissolution–crystallization processes during cement stone formation. Materials obtained in the CaO-K2O-SO3-H2O system consisting of biocompatible and resorbable (soluble in water) phases can be recommended for testing as potential substances for bone defect treatments.
Synthesis of the Bipyridine-Type Ligand 3-(2-Pyridyl)-5,6-diphenyl-1,2,4-triazine and Structural Elucidation of Its Cu(I) and Ag(I) Complexes
Authors: Hatzidimitriou Antonios , Stamatiou Antonios , Tzimopoulos Dimitrios , Akrivos Pericles D.
Published: July 2023

The synthesis of a substituted diimine with a bipydirine-type backbone, (3-(2-pyridyl)-5,6-diphenyl-1,2,4-triazine, L) and its coordination towards Cu(I) and Ag(I) is studied in the presence of diphosphine ligand bis(diphenylphosphino)methane, dppm. The metal complexes are characterized by IR, 1H, and 13C NMR and single crystal X ray diffraction studies. They are dinuclear, as they are held by diphosphine bridges between the tetrahedral metal centers, forming eight-membered ring with the participation of the bridging diphosphinomethane ligands. Within each ring, the planar orientations of M2P2 and of all four P atoms are realized. Solid state excitation spectra are dominated by metal-to-ligand charge transfer bands (MLCT), while geometry relaxation permits only low-intensity emission for the copper compound.
Stoichiometric and Nonstoichiometric Surface Structures of Pyrochlore Y2Zr2O7 and Their Relative Stabilities: A First-Principles Investigation
Authors: Wu Huajian , Zhang Jianning , Wang Yiren , Shang Jiacheng , Jiang Yong
Published: July 2023

First-principle total energy calculations were performed to investigate the atomic structures and relative stabilities of two low miller-index surfaces of pyrochlore Y2Zr2O7. The stoichiometric Y2Zr2O7 (110) and (100) surfaces were predicted, with lowest formation energies of 1.20 and 1.47 J/m2, respectively. Based on a thermodynamic defect model, non-stoichiometric Y2Zr2O7 surface energies were further evaluated as a function of environmental oxygen partial pressure (pO2) and temperature (T). With all of the results, we were able to construct the surface phase diagrams for T = 300 and 1400 K. The strong correlation between the structural stabilities and the surface stoichiometry was revealed as varying T and pO2. At a given T, the most stable termination of the (110) surfaces would change from a (Y,Zr)−rich (ns−2Y2Zr6O) to O−rich ones (ns−4O_2 and ns−4O_1) as increasing pO2, while that of the (100) surfaces would change from the stoichiometric (stoi−1Y1Zr_1) to the O−rich one (ns−5O). The critical pO2 value for termination transition moves to its higher end as increasing T.
Evaluation of Curing Effects on Bitumen Emulsion-Based Cold In-Place Recycling Mixture Considering Field-Water Evaporation and Heat-Transfer Conditions
Authors: Zhao Zili , Ni Fujian , Zheng Junqiu , Cheng Zhiqiang , Xie Shengjia
Published: July 2023

The strength growth of a bitumen emulsion-based cold in-place recycling asphalt mixture (BE-CIR) is time-dependent and time-consuming due to the addition of water. There is a great difference between the curing conditions of specification in the laboratory and the in situ conditions, which often leads to a great discrepancy between the results of lab specimens and the field cores. The main objective of this paper is to evaluate the curing effect on laboratory BE-CIR considering field-water evaporation and heat-transfer conditions. Four different curing methods were designed by using different combinations of waterproof layers, heat insulation layers, and variable temperature modes. The variations in temperature indexes, moisture content, air void, and indirect tensile strength (ITS) with curing time were tested, and the mutual influence of these indicators was analyzed. Furthermore, the results of the laboratory samples were compared with the field cores. Testing results show that the performance of the BE-CIR mixture is significantly different from that with no treatment, which is manifested as higher moisture content and lower air void and ITS under the same curing time. The internal temperature of the mixture is the main factor affecting the variation of moisture content, especially on the first curing day. The air void of the mixture has a strong linear relationship with the moisture content. Moisture content and ITS under different curing methods showed similar trends and could be divided into two stages. Taking the field cores as a benchmark, it can be concluded that the field-water evaporation condition should be considered in the setting of indoor curing methods, while the heat transfer could not.
Study on the Anisotropy of Triply Periodic Minimal Surface Porous Structures
Authors: Zhang Mingkang , Li Jinwei , Liu Chang , Deng Mingjian , Liao Xing , Wang Di
Published: July 2023

Because their topological structures have certain crystallographic symmetry, there is anisotropy in triply periodic minimal surface (TPMS) porous structures. Anisotropy can affect the mechanical properties of porous structures; thus, it is necessary to research the anisotropy of TPMS structures. In this study, based on quaternionic three-dimensional rotation, TPMS structures were rotated around three crystal directions: [100], [110], and [111]. The mechanical anisotropy behaviors of TPMS porous structures, including gyroid, diamond, primitive, and I-graph-wrapped package (IWP) graph surfaces, were studied through finite element analysis (FEA). The FEA results show that the anisotropy of the IWP structure with rotation in the [110] direction was the most significant, and its relative elastic modulus increased by 275.33% when the IWP was rotated 60° in the [110] direction. These results indicate that the uniaxial compression performance of TPMS structures can be significantly improved by using structural anisotropy. However, it should be noted that due to this significant anisotropy, the performance of such structures will significantly decrease in specific directions. For example, after the primitive structure was rotated 60° in the [111] and [110] directions, its relative elastic modulus decreased by 72.66% and 77.6%, respectively. Therefore, it was necessary to reasonably consider the bearing capacity in fragile directions under complex working conditions. Based on the anisotropy of TPMS, gradient TPMS structures with three rotation angles were designed and manufactured using selective laser melting technology. The compressive results show that multi-peaks appeared in the primitive structure with gradient rotation in the [111] direction from 0° to 40°, and step-by-step behaviors were observed in the IWP structure with gradient rotation in the [110] direction from 0° to 60°. This result shows that the yielding platform can be enhanced using gradient rotation designation based on the anisotropy of TPMS porous structures.
Ring-Core Photonic Crystal Fiber Sensor Based on SPR for Extra-Wide Refractive Index Detection
Authors: He Jie , Wang Jianxin , Yang Lin , Lv Jingwei , Liu Wei , Liu Qiang , Chu Paul K. , Liu Chao
Published: July 2023

Spurred by the rapid development of fiber optic sensing technology, photonic crystal fiber (PCF) sensors based on surface plasmon resonance (SPR) have received widespread attention. However, they can only detect a narrow range, and the coating process is complex. Herein, a wide-range SPR sensor is designed. It consists of a ring-core PCF filled with plasmonic materials. Compared to the process of depositing a coating inside the air hole, the analyte and gold nanowires fill our PCF, thus simplifying the manufacturing complexity. The ring-core structure enhances the directional power transmission between the guided mode and the surface plasmon polariton (SPP) mode. The sensor is numerically analyzed using the finite element method (FEM). The results show that the PCF-SPR sensor has a wavelength sensitivity and amplitude sensitivity of 40,000 nm/RIU and 2141 RIU−1, and the resolution is 2.5 × 10−6 RIU−1 for the detection range of 1.13–1.45. The high-sensitivity sensor boasting a wide refractive index detection range performs better than conventional solid-core PCF-SPR sensors, boding well for biochemical sensing.
Piezoelectric Materials Design for High-Performance Sensing
Authors: Deng Weili , Jin Long , Yang Weiqing
Published: July 2023

Piezoelectric materials can realize the mutual conversion of electrical energy and mechanical energy, and are widely used in electronic devices such as piezoelectric filters, micro-displacers, actuators, and sensors, which have crucial uses in the fields of information and communication, biomedicine, military defense, etc [...]