bluuebunny/crossref_metadata_2025 huggingface dataset:
Research on Multi-Scale Feature Extraction and Working Condition Classification Algorithm of Lead-Zinc Ore Flotation Foam
Authors: Jiang Xiaoping , Zhao Huilin , Liu Junwei , Ma Suliang , Hu Mingzhen
Published: March 2023

To address the problems of difficult online monitoring, low recognition efficiency and the subjectivity of work condition identification in mineral flotation processes, a foam flotation performance state recognition method is developed to improve the issues mentioned above. This method combines multi-dimensional CNN (convolutional neural networks) characteristics and improved LBP (local binary patterns) characteristics. We have divided the foam flotation conditions into six categories. First, the multi-directional and multi-scale selectivity and anisotropy of nonsubsampled shearlet transform (NSST) are used to decompose the flotation foam images at multiple frequency scales, and a multi-channel CNN network is designed to extract static features from the images at different frequencies. Then, the flotation video image sequences are rotated and dynamic features are extracted by the LBP-TOP (local binary patterns from three orthogonal planes), and the CNN-extracted static picture features are fused with the LBP dynamic video features. Finally, classification decisions are made by a PSO-RVFLNs (particle swarm optimization-random vector functional link networks) algorithm to accurately identify the foam flotation performance states. Experimental results show that the detection accuracy of the new method is significantly improved by 4.97% and 6.55%, respectively, compared to the single CNN algorithm and the traditional LBP algorithm, respectively. The accuracy of flotation performance state classification was as high as 95.17%, and the method reduced manual intervention, thus improving production efficiency.
Understanding Temporal Patterns and Determinants of Ground-Level Ozone
Authors: Wang Junshun , Dong Jin , Guo Jingxian , Cai Panli , Li Runkui , Zhang Xiaoping , Xu Qun , Song Xianfeng
Published: March 2023

Ground-level ozone pollution causes adverse health effects, and the detailed influences of meteorological factors and precursors on ozone at an hourly scale need to be further understood. We conducted an in-depth analysis of the phase relationships and periods of ground-level ozone in Shunyi station, Beijing, and contributing factors using wavelet analysis and geographic detectors in 2019. The combined effects of different factors on ozone were also calculated. We found that temperature had the strongest influence on ozone, and they were in phase over time. NO2 had the greatest explanatory power for the temporal variations in ozone among precursors. The wavelet power spectrum indicated that ozone had a periodic effect on multiple time scales, the most significant being the 22–26 h period. The wavelet coherence spectrum showed that in January–March and October–December, NO2 and ozone had an antiphase relationship, largely complementary to the in-phase relationship of temperature and ozone. Thus, the main influencing factors varied during the year. The interactions of temperature with NO2 significantly affected the temporal variations in ozone, and explanatory power surpassed 70%. The findings can deepen understanding of the effects of meteorological factors and precursors on ozone and provide suggestions for mitigating ozone pollution.
Canine Coronavirus Infection Modulates the Biogenesis and Composition of Cell-Derived Extracellular Vesicles
Authors: Pandit Rachana , Ipinmoroti Ayodeji O. , Crenshaw Brennetta J. , Li Ting , Matthews Qiana L.
Published: March 2023

Coronavirus (CoV) has persistently become a global health concern causing various diseases in a wide variety of hosts, including humans, birds, and companion animals. However, the virus-mediated responses in animal hosts have not been studied extensively due to pathogenesis complexity and disease developments. Extracellular vesicles (EVs) are widely explored in viral infections for their intercellular communication, nanocarrier, and immunomodulatory properties. We proposed that coronavirus hijacks the host exosomal pathway and modulates the EV biogenesis, composition, and protein trafficking in the host. In the present study, Crandell–Rees feline kidney (CRFK) cells were infected with canine coronavirus (CCoV) in an exosome-free medium at the multiplicity of infection (MOI) of 400 infectious units (IFU) at various time points. The cell viability was significantly decreased over time, as determined by the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Post-infection EVs were isolated, and transmission electron microscopy (TEM) showed the presence of small EVs (sEVs) after infection. NanoSight particle tracking analysis (NTA) revealed that EV sizes averaged between 100 and 200 nm at both incubation times; however, the mean size of infection-derived EVs was significantly decreased at 48 h when compared to uninfected control EVs. Quantitative analysis of protein levels performed by dot blot scanning showed that the expression levels of ACE-2, annexin-V, flotillin-1, TLR-7, LAMP, TNF-α, caspase-1, caspase-8, and others were altered in EVs after infection. Our findings suggested that coronavirus infection impacts cell viability, modulates EV biogenesis, and alters cargo composition and protein trafficking in the host, which could impact viral progression and disease development. Future experiments with different animal CoVs will provide a detailed understanding of host EV biology in infection pathogenesis and progression. Hence, EVs could offer a diagnostic and therapeutic tool to study virus-mediated host responses that could be extended to study the interspecies jump of animal CoVs to cause infection in humans.
Single Nucleotide Polymorphisms of the RAC1 Gene as Novel Susceptibility Markers for Neuropathy and Microvascular Complications in Type 2 Diabetes
Authors: Azarova Iuliia , Klyosova Elena , Polonikov Alexey
Published: March 2023

Single nucleotide polymorphisms (SNP) in the RAC1 (Rac family small GTPase 1) gene have recently been linked to type 2 diabetes (T2D) and hyperglycemia due to their contribution to impaired redox homeostasis. The present study was designed to determine whether the common SNPs of the RAC1 gene are associated with diabetic complications such as neuropathy (DN), retinopathy (DR), nephropathy, angiopathy of the lower extremities (DA), and diabetic foot syndrome. A total of 1470 DNA samples from T2D patients were genotyped for six common SNPs by the MassArray Analyzer-4 system. The genotype rs7784465-T/C of RAC1 was associated with an increased risk of DR (p = 0.016) and DA (p = 0.03) in males, as well as with DR in females (p = 0.01). Furthermore, the SNP rs836478 showed an association with DR (p = 0.005) and DN (p = 0.025) in males, whereas the SNP rs10238136 was associated with DA in females (p = 0.002). In total, three RAC1 haplotypes showed significant associations (FDR < 0.05) with T2D complications in a sex-specific manner. The study’s findings demonstrate, for the first time, that the RAC1 gene’s polymorphisms represent novel and sex-specific markers of neuropathy and microvascular complications in type 2 diabetes, and that the gene could be a new target for the pharmacological inhibition of oxidative stress as a means of preventing diabetic complications.
Immunohistochemical Evaluation of Candidate Biomarkers for Fluorescence-Guided Surgery of Myxofibrosarcoma Using an Objective Scoring Method
Authors: Rijs Zeger , Belt Esther , Kalisvaart Gijsbert M. , Sier Cornelis F. M. , Kuppen Peter J. K. , Cleven Arjen H. G. , Vahrmeijer Alexander L. , van de Sande Michiel A. J. , van Driel Pieter B. A. A.
Published: March 2023

Introduction: Myxofibrosarcoma (MFS) is the most common soft-tissue sarcoma subtype in elderly patients. Local recurrence (LR) remains a major concern as the lack of intraoperative guidance and an infiltrative growth pattern with long, slender tails hamper surgeons’ ability to achieve adequate resection margins for MFS. Fluorescence-guided surgery (FGS) could overcome this concern by delineating tumor tissue during surgery. One of the most important steps to successful FGS is to define a tumor-specific biomarker that is highly overexpressed in tumor tissue while low or absent in adjacent healthy tissue. The aim of this study is to evaluate the expression of eight previously selected promising biomarkers for FGS in MFS tissue samples with adjacent healthy tissue using immunohistochemistry (IHC). Methods: The following eight biomarkers were stained in seventeen paraffin-embedded MFS samples: tumor endothelial marker-1 (TEM-1, also known as endosialin/CD248), vascular endothelial growth factor receptor-1 (VEGFR-1, also known as Flt-1), vascular endothelial growth factor receptor-2 (VEGFR-2, also known as Flk1), vascular endothelial growth factor-A (VEGF-A), epidermal growth factor receptor (EGFR), insulin-like growth factor-1 receptor (IGF-1R), platelet derived growth factor receptor-α (PDGFR-α), and cluster of differentiation 40 (CD40, also known as TNFRSF5). A pathologist specializing in sarcoma annotated the margin between the tumor and adjacent healthy tissue in each MFS tissue sample. Subsequently, we used an objective IHC scoring method to assess and compare the difference in staining intensity between the tumor and adjacent healthy tissue, which is crucial for the use of FGS. Results: TEM-1, VEGF-A, and PDGFR-α stained all MFS tumors, while the other biomarkers did not show expression in all MFS tumors. Ultimately, TEM-1 was identified as the most suitable biomarker for FGS in MFS based on higher tumor-to-background (TBR) staining intensity compared to VEGF-A and PDGFR-α, regardless of preoperative therapy. Conclusion: TEM-1-targeted FGS tracers should be further investigated to optimize MFS treatment.
Preventive Strategies for Cognitive Decline and Dementia: Benefits of Aerobic Physical Activity, Especially Open-Skill Exercise
Authors: Yamasaki Takao
Published: March 2023

As there is no curative treatment for dementia, including Alzheimer’s disease (AD), it is important to establish an optimal nonpharmaceutical preventive intervention. Physical inactivity is a representative modifiable risk factor for dementia, especially for AD in later life (>65 years). As physical activity and exercise are inexpensive and easy to initiate, they may represent an effective nonpharmaceutical intervention for the maintenance of cognitive function. Several studies have reported that physical activity and exercise interventions are effective in preventing cognitive decline and dementia. This review outlines the effects of physical activity and exercise-associated interventions in older adults with and without cognitive impairment and subsequently summarizes their possible mechanisms. Furthermore, this review describes the differences between two types of physical exercise—open-skill exercise (OSE) and closed-skill exercise (CSE)—in terms of their effects on cognitive function. Aerobic physical activity and exercise interventions are particularly useful in preventing cognitive decline and dementia, with OSE exerting a stronger protective effect on cognitive functions than CSE. Therefore, the need to actively promote physical activity and exercise interventions worldwide is emphasized.
Usability and Biomechanical Testing of Passive Exoskeletons for Construction Workers: A Field-Based Pilot Study
Authors: Bennett Sean T. , Han Wei , Mahmud Dilruba , Adamczyk Peter G. , Dai Fei , Wehner Michael , Veeramani Dharmaraj , Zhu Zhenhua
Published: March 2023

The labor-intensive nature of the construction industry requires workers to frequently perform physically demanding manual work, thereby exposing them to the risk of musculoskeletal injury (approximately 31.2 cases per 10,000 full-time equivalent workers). Exoskeletons and exosuits (collectively called EXOs here) are designed to protect workers from these injuries by reducing exertion and muscle fatigue during work. However, the usability of EXOs in construction is still not clear. This is because extant EXO assessments in construction were mainly conducted in laboratory environments with test participants who are not construction professionals. In this research, we conducted a pilot study to investigate the usability of EXOs in a real construction workplace. Four experienced workers were recruited to push/empty construction gondolas with and without a Back-Support EXO, HeroWear Apex. Three workers were recruited to install/remove wooden blocks between steel studs with and without two Arm-Support EXOs, i.e., Ekso EVO and Hilti EXO-001. Their motions, postures, heart rates, and task completion times were recorded and compared. The workers were also surveyed to gather their attitudes toward the EXO’s usefulness and ease of use. The study results demonstrated that the workers responded to the use of EXOs differently and consequently were not unanimously in favor of EXO adoption in practice. The preliminary results and findings from this pilot study help in building a foundation of understanding to improve EXO products to fit the needs of construction workers and foster EXO-enabled construction tasks in the future.
Experimental and Numerical Investigation of the Behavior of Steel Beams Strengthened by Bolted Hybrid FRP Composites
Authors: AbouEl-Hamd Omnia R. , Sweedan Amr M. I. , El-Ariss Bilal , El-Sawy Khaled M.
Published: March 2023

The strengthening of steel beams using hybrid fiber-reinforced polymers (HFRPs) has gained enormous attention over the last decades. Few researchers have investigated the effectiveness of the fastening techniques without a bonding agent to overcome the undesirable debonding failure of the bonded FRP–steel system. This paper reports the outcomes of experimental and numerical investigations conducted on steel beams strengthened by HFRP using steel bolts. Twenty-two steel beams were tested in four-point loading to investigate the effect of the HFRP length and the bolt arrangement on the flexural behavior of the strengthened systems. The observed failure modes, load-deflection relations, deflection profiles, and strain measurements were also studied. The tested beams showed a ductile behavior, with 15.1 and 22.2% enhancements in the yield and ultimate flexural capacities, respectively. Simplified empirical equations were developed to predict the ultimate load of the bolted HFRP–steel beams. ANSYS software was used to model the beams’ behavior and investigate the effects of the HFRP thickness, bolt spacing, steel grade, loading scheme, and beam length on the effectiveness of the adopted fastening technique. Increasing the HFRP length enhanced the utilization of HFRPs as well as the beam’s ductility, with a reduction of up to 51.2% in the mid-span deflection. Moreover, the strain compatibility of the HFRP–steel beams was improved with an 87.2% reduction in the interfacial slippage. The bolt arrangement showed an insignificant effect on the overall performance of the beams. The numerical results verified the effectiveness of the fastening technique in enhancing the flexural performance of the steel beams, with gains of up to 16.7% and 34.5% in the yield and ultimate load-carrying capacities, respectively.
Fostering Digitalization of Construction Projects through Integration: A Conceptual Project Governance Model
Authors: Liu Zhixue , Ding Ronggui , Gong Zheng , Ejohwomu Obuks
Published: March 2023

The construction industry has fared poorly in the process of digital transformation, while the main challenge is the digitalization of construction projects. Changes in project management approaches are urgently required in construction organizations to better align digital technology and organizational conditions. However, little literature has explored the pivotal role of the project management approach from an organizational perspective. To fill this gap, this research investigates ways of using a project governance model for integration to promote the digitalization of construction projects through a case study. The three integration dimensions, namely stakeholder integration, lifecycle integration, and project management knowledge integration, are identified, and governance elements under each dimension are displayed—and further stratified—based on the three levels of the governance model, including institutional level, organizational level, and behavioral level. The logical relationship between elements and their roles in project digitization is finally summarized. The developed conceptual model will provide an approach for construction enterprises to promote project digitalization.
Design and Implementation of a Futuristic EV Energy Trading System (FEETS) Connected with Buildings, PV, and ESS for a Carbon-Neutral Society
Authors: Park Sangmin , Park SeolAh , Yun Sang-Pil , Lee Kyungeun , Kang Byeongkwan , Choi Myeong-in , Jang Hyeonwoo , Park Sehyun
Published: March 2023

To realize carbon neutrality, understanding the energy consumed in the building sector, which is more than that in other sectors, such as industry, agriculture, and commerce, is pivotal. Approximately 37% of energy consumption belongs to the building sector, and management of building energy is a critical factor. In this paper, we present an energy sharing scenario for energy stabilization, assuming that electric vehicles and their charging stations are widely distributed in the future. Consequently, fewer fuel cars will exist, and electric cars will become the major mode of transportation. Therefore, it is essential to install charging stations for electric vehicles in the parking lots of future buildings, and business models are expected to expand. In this paper, we introduce a future energy stabilization mechanism for peak power management in buildings and present a platform that entails connection-based energy trading technology based on a scenario. We also propose an energy supply strategy to prevent excess prices incurred due to peak consumption. Then, we analyzed the electricity bill for one month through scenario-based simulations of an existing building and the proposed system. When applying the proposed system, we derived a result that can reduce electricity rates by 38.3% (best case) to 78.5% (worst case) compared with the existing rates.
Identifying Collapsible Soils from Seismic Cone (SCPT): A Qualitative Approach
Authors: Rocha Breno Padovezi , Silveira Isabela Augusto , Rodrigues Roger Augusto , Lodi Paulo Cesar , Giacheti Heraldo Luiz
Published: March 2023

Collapsible soils are unsaturated low-density soils that undergo abrupt settlement when flooded without any increase in the in-situ stress level. The first stage of the site characterization is identifying collapsible soils, since these are problematic soils. Seismic cone testing (SCPT) has been increasingly used for site characterization, because it allows combining stratigraphic logging with the maximum shear modulus (G0) determination. In this paper, laboratory and in-situ tests carried out at 21 sites with collapsible and non-collapsible soils are interpreted to differentiate between such soils, based on the seismic cone test (SCPT). Collapsible soils have G0/qc values greater than 23 and qc1 values less than 70, while non-collapsible soils have G0/qc values less than 23 and qc1 values greater than 70. The investigated collapsible soils have microstructure (bonding/cementation), but the classical approach cannot be sufficient to identify collapsible soils alone. An approach was used to identify collapsible soils based on maximum shear modulus (G0), normalized cone resistance (qc1), and cone resistance (qc). The chart G0/qc versus qc1 and boundaries is an alternative for distinguishing between collapsible and non-collapsible soils in the early stage of site investigation. This qualitative approach should be used in the preliminary investigation phase to select potentially collapsible soils and helps guide the sampling of potentially collapsible soils for laboratory testing. Further SCPT data from different soil types, particularly the collapsible ones, are valuable to adjust or confirm the boundary equations suggested.
Nanocomposites Produced with the Addition of Carbon Nanotubes Dispersed on the Surface of Cement Particles Using Different Non-Aqueous Media
Authors: Rocha Vanessa Vilela , Bacelar Bruno Athaíde , Coelho Isabela Domingues , Ludvig Péter
Published: March 2023

The inclusion of carbon nanotubes (CNTs) in cementitious composites has been studied due to their electrical, thermal, and mechanical enhancing properties. Considering the hydrophobic characteristics of CNTs, these nanomaterials need to be well dispersed in the aqueous media in which they are inserted to guarantee those gains. Among the methods applied to produce such composites is the dispersion of CNTs on the surface of anhydrous cement particles using non-aqueous suspensions such as acetone, ethanol, or isopropanol. Even though those non-aqueous media have been individually studied by researchers, comparisons of the efficiency of CNTs dispersion was not found in the literature. Therefore, as a novelty, the present article aims to analyze the influence of the addition of the multi-walled CNTs dispersed in the cited three types of non-aqueous suspensions on the cement paste’s electrical and mechanical properties. Pastes containing 0%, 0.5%, and 1.0% of CNTs were prepared on the surface of anhydrous cement particles using a pre-dispersion technique based on simultaneous sonication and mechanical agitation in the three cited media. Tests to determine electric-volumetric resistivity, compressive strength, and splitting tensile strength were performed. It was observed that acetone dispersion decreases the cement paste’s electrical resistivity, even without the addition of CNTs. The cementitious composites with CNTs demonstrated increased mechanical strength (both compressive and tensile) using all three dispersion media. Statistical analysis (analysis of variance—ANOVA—and Tukey’s Test) was performed to evaluate the significance of the results.
Quantitative Biomarkers Derived from a Novel Contrast-Free Ultrasound High-Definition Microvessel Imaging for Distinguishing Thyroid Nodules
Authors: Kurti Melisa , Sabeti Soroosh , Robinson Kathryn A. , Scalise Lorenzo , Larson Nicholas B. , Fatemi Mostafa , Alizad Azra
Published: March 2023

Low specificity in current ultrasound modalities for thyroid cancer detection necessitates the development of new imaging modalities for optimal characterization of thyroid nodules. Herein, the quantitative biomarkers of a new high-definition microvessel imaging (HDMI) were evaluated for discrimination of benign from malignant thyroid nodules. Without the help of contrast agents, this new ultrasound-based quantitative technique utilizes processing methods including clutter filtering, denoising, vessel enhancement filtering, morphological filtering, and vessel segmentation to resolve tumor microvessels at size scales of a few hundred microns and enables the extraction of vessel morphological features as new tumor biomarkers. We evaluated quantitative HDMI on 92 patients with 92 thyroid nodules identified in ultrasound. A total of 12 biomarkers derived from vessel morphological parameters were associated with pathology results. Using the Wilcoxon rank-sum test, six of the twelve biomarkers were significantly different in distribution between the malignant and benign nodules (all p < 0.01). A support vector machine (SVM)-based classification model was trained on these six biomarkers, and the receiver operating characteristic curve (ROC) showed an area under the curve (AUC) of 0.9005 (95% CI: [0.8279,0.9732]) with sensitivity, specificity, and accuracy of 0.7778, 0.9474, and 0.8929, respectively. When additional clinical data, namely TI-RADS, age, and nodule size were added to the features, model performance reached an AUC of 0.9044 (95% CI: [0.8331,0.9757]) with sensitivity, specificity, and accuracy of 0.8750, 0.8235, and 0.8400, respectively. Our findings suggest that tumor vessel morphological features may improve the characterization of thyroid nodules.
Novel Generation of FAP Inhibitor-Based Homodimers for Improved Application in Radiotheranostics
Authors: Martin Marcel , Ballal Sanjana , Yadav Madhav Prasad , Bal Chandrasekhar , Van Rymenant Yentl , De Loose Joni , Verhulst Emile , De Meester Ingrid , Van Der Veken Pieter , Roesch Frank
Published: March 2023

Radiopharmaceuticals based on the highly potent FAP inhibitor (FAPi) UAMC-1110 have shown great potential in molecular imaging, but the short tumor retention time of the monomers do not match the physical half-lives of the important therapeutic radionuclides 177Lu and 225Ac. This was improved with the dimer DOTAGA.(SA.FAPi)2, but pharmacological and radiolabeling properties still need optimization. Therefore, the novel FAPi homodimers DO3A.Glu.(FAPi)2 and DOTAGA.Glu.(FAPi)2. were synthesized and quantitatively radiolabeled with 68Ga, 90Y, 177Lu and 225Ac. The radiolabeled complexes showed high hydrophilicity and were generally stable in human serum (HS) and phosphate-buffered saline (PBS) at 37 °C over two half-lives, except for [225Ac]Ac-DOTAGA.Glu.(FAPi)2 in PBS. In vitro affinity studies resulted in subnanomolar IC50 values for FAP and high selectivity for FAP over the related proteases PREP and DPP4 for both compounds as well as for [natLu]Lu-DOTAGA.Glu.(FAPi)2. In a first proof-of-principle patient study (medullary thyroid cancer), [177Lu]Lu-DOTAGA.Glu.(FAPi)2 was compared to [177Lu]Lu-DOTAGA.(SA.FAPi)2. High uptake and long tumor retention was observed in both cases, but [177Lu]Lu-DOTAGA.Glu.(FAPi)2 significantly reduces uptake in non-target and critical organs (liver, colon). Overall, the novel FAPi homodimer DOTAGA.Glu.(FAPi)2 showed improved radiolabeling in vitro and pharmacological properties in vivo compared to DOTAGA.(SA.FAPi)2. [177Lu]Lu-DOTAGA.Glu.(FAPi)2 and [225Ac]Ac-DOTAGA.Glu.(FAPi)2 appear promising for translational application in patients.
Current Understanding of Microbiomes in Cancer Metastasis
Authors: Liu Jiaqi , Luo Feiyang , Wen Liyan , Zhao Zhanyi , Sun Haitao
Published: March 2023

Cancer has been the first killer that threatens people’s lives and health. Despite recent improvements in cancer treatment, metastasis continues to be the main reason for death from cancer. The functions of microbiome in cancer metastasis have been studied recently, and it is proved that microbiome can influence tumor metastasis, as well as positive or negative responses to therapy. Here, we summarize the mechanisms of microorganisms affecting cancer metastasis, which include epithelial-mesenchymal transition (EMT), immunity, fluid shear stress (FSS), and matrix metalloproteinases (MMPs). This review will not only give a further understanding of relationship between microbiome and cancer metastasis, but also provide a new perspective for the microbiome’s application in cancer metastasis prevention, early detection, and treatment.
Comparison of Hormone-Sensitive Oligorecurrent Prostate Cancer Patients Based on Routine Use of Choline and/or PSMA PET/CT to Guide Metastasis-Directed Therapy
Authors: Metz Raphaël , Rauscher Aurore , Vaugier Loïg , Supiot Stéphane , Drouet Franck , Campion Loic , Rousseau Caroline
Published: March 2023

Background: In hormone-sensitive oligorecurrent prostate cancer (PC), the literature showed [68Ga]Ga-PSMA (PSMA) and [18F]F-choline (FCH) PET/CT can successfully guide metastasis-directed therapies (MDT). This observational retrospective study aimed to explore, in routine use, the impact of FCH or PSMA PET/CT in guiding MDT for hormone-sensitive oligometastatic PC at different recurrences. Methods: In 2017–2020, patients initially treated with radical prostatectomy but, in biochemical recurrence (with PSA ≤ 2 ng/mL), diagnosed as oligometastatic based on FCH or PSMA PET/CT, were identified. MDT was stereotactic body radiotherapy (SBRT), elective nodal or prostate bed radiotherapy ± boost and ± androgen deprivation therapy (ADT). The primary endpoint was biochemical relapse-free survival (BR-FS), defined as a PSA increase ≥ 0.2 ng/mL above the nadir and increasing over two successive samples and the secondaries were ADT-free survival (ADT-FS). Results: 123 patients (70 PSMA and 53 FCH) were included. The median follow-up was 42.2 months. The median BR-FS was 24.7 months in the PSMA group versus 13.0 months in the FCH group (p = 0.008). Similarly, ADT-FS (p = 0.001) was longer in patients in the PSMA group. In multivariate analysis, a short PSA doubling time before imaging (p = 0.005) and MDT with SBRT (p = 0.001) were poor prognostic factors for BR-FS. Conclusions: Routine use of FCH or PSMA PET/CT in hormone-sensitive PC showed an advantage for using PSMA PET/CT to guide MDT in terms of BR-FS and ADT-FS in patients with low PSA value. Prospective studies are needed to confirm these hypotheses.
Examination of the Functional Relationship between PD-L1 DNA Methylation and mRNA Expression in Non-Small-Cell Lung Cancer
Authors: Larsen Trine V. , Dybdal Nina , Daugaard Tina F. , Lade-Keller Johanne , Lin Lin , Sorensen Boe S. , Nielsen Anders L.
Published: March 2023

Immunotherapy targeting the interaction between programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) is a treatment option for patients with non-small-cell lung cancer (NSCLC). The expression of PD-L1 by the NSCLC cells determines treatment effectiveness, but the relationship between PD-L1 DNA methylation and expression has not been clearly described. We investigated PD-L1 DNA methylation, mRNA expression, and protein expression in NSCLC cell lines and tumor biopsies. We used clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR-Cas9) to modify PD-L1 genetic contexts and endonuclease deficient Cas9 (dCas9) fusions with ten-eleven translocation methylcytosine dioxygenase 1 (TET1) and DNA (cytosine-5)-methyltransferase 3A (DNMT3A) to manipulate PD-L1 DNA methylation. In NSCLC cell lines, we identified specific PD-L1 CpG sites with methylation levels inversely correlated with PD-L1 mRNA expression. However, inducing PD-L1 mRNA expression with interferon-γ did not decrease the methylation level for these CpG sites, and using CRISPR-Cas9, we found that the CpG sites did not directly confer a negative regulation. dCas9-TET1 and dCas9-DNMT3A could induce PD-L1 hypo- and hyper-methylation, respectively, with the latter conferring a decrease in expression showing the functional impact of methylation. In NSCLC biopsies, the inverse correlation between the methylation and expression of PD-L1 was weak. We conclude that there is a regulatory link between PD-L1 DNA methylation and expression. However, since these measures are weakly associated, this study highlights the need for further research before PD-L1 DNA methylation can be implemented as a biomarker and drug target for measures to improve the effectiveness of PD-1/PD-L1 immunotherapy in NSCLC.
Effect of MgFe-LDH with Reduction Pretreatment on the Catalytic Performance in Syngas to Light Olefins
Authors: Li Jie , Li Changxiao , Tang Qiong , Zuo Zhijun , Liu Lei , Dong Jinxiang
Published: March 2023

MgFe-layered double hydroxides (LDH) were widely used as catalysts for Fischer–Tropsch synthesis to produce light olefins, in which the state of Fe-species may affect the resulting catalytic active sites. Herein, the typical MgFe-LDH was hydrothermally synthesized and the obtained MgFe-LDH was pretreated with H2 at different temperatures to reveal the effects of the state of Fe-species on the catalytic performance in Fischer–Tropsch synthesis. MgFe-LDH materials were characterized by X-ray diffraction (XRD), N2 adsorption–desorption, scanning electron microscopy (SEM), transmission electron microscopy (TEM), H2 temperature-programmed reduction (H2-TPR), and X-ray photoelectron spectroscopy (XPS). It was found that a MgO-FeO solid solution would be formed with the increase of the reduction temperature, which made the electrons transfer from Mg atoms to Fe atoms and strengthened the adsorption of CO. The pre-reduced treatment toward Mg-Fe-LDH enabled the FeCx active sites to be easily formed in situ during the reaction process, leading to the high conversion of CO. CO2 temperature-programmed desorption (CO2-TPD) and H2 temperature-programmed desorption (H2-TPD) analysis confirmed that the surface basicity of the catalysts was increased and the hydrogenation capacity was weakened, the secondary hydrogenation of the olefins was inhibited, and therefore as were the enhancement of O/P in the product and the high selectivity of light olefins (42.7%).
The Similar and Distinct Roles of Satellite Glial Cells and Spinal Astrocytes in Neuropathic Pain
Authors: McGinnis Aidan , Ji Ru-Rong
Published: March 2023

Preclinical studies have identified glial cells as pivotal players in the genesis and maintenance of neuropathic pain after nerve injury associated with diabetes, chemotherapy, major surgeries, and virus infections. Satellite glial cells (SGCs) in the dorsal root and trigeminal ganglia of the peripheral nervous system (PNS) and astrocytes in the central nervous system (CNS) express similar molecular markers and are protective under physiological conditions. They also serve similar functions in the genesis and maintenance of neuropathic pain, downregulating some of their homeostatic functions and driving pro-inflammatory neuro-glial interactions in the PNS and CNS, i.e., “gliopathy”. However, the role of SGCs in neuropathic pain is not simply as “peripheral astrocytes”. We delineate how these peripheral and central glia participate in neuropathic pain by producing different mediators, engaging different parts of neurons, and becoming active at different stages following nerve injury. Finally, we highlight the recent findings that SGCs are enriched with proteins related to fatty acid metabolism and signaling such as Apo-E, FABP7, and LPAR1. Targeting SGCs and astrocytes may lead to novel therapeutics for the treatment of neuropathic pain.
VEGF Stimulates Activation of ERK5 in the Absence of C-Terminal Phosphorylation Preventing Nuclear Localization and Facilitating AKT Activation in Endothelial Cells
Authors: Mondru Anil Kumar , Aljasir Mohammad A. , Alrumayh Ahmed , Nithianandarajah Gopika N. , Ahmed Katie , Muller Jurgen , Goldring Christopher E. P. , Wilm Bettina , Cross Michael J.
Published: March 2023

Extracellular-signal-regulated kinase 5 (ERK5) is critical for normal cardiovascular development. Previous studies have defined a canonical pathway for ERK5 activation, showing that ligand stimulation leads to MEK5 activation resulting in dual phosphorylation of ERK5 on Thr218/Tyr220 residues within the activation loop. ERK5 then undergoes a conformational change, facilitating phosphorylation on residues in the C-terminal domain and translocation to the nucleus where it regulates MEF2 transcriptional activity. Our previous research into the importance of ERK5 in endothelial cells highlighted its role in VEGF-mediated tubular morphogenesis and cell survival, suggesting that ERK5 played a unique role in endothelial cells. Our current data show that in contrast to EGF-stimulated HeLa cells, VEGF-mediated ERK5 activation in human dermal microvascular endothelial cells (HDMECs) does not result in C-terminal phosphorylation of ERK5 and translocation to the nucleus, but instead to a more plasma membrane/cytoplasmic localisation. Furthermore, the use of small-molecule inhibitors to MEK5 and ERK5 shows that instead of regulating MEF2 activity, VEGF-mediated ERK5 is important for regulating AKT activity. Our data define a novel pathway for ERK5 activation in endothelial cells leading to cell survival.
The Microstructure Evolution and Dynamic Recrystallization Mechanism of Cu-1.1–Ni-0.7–Co-0.45–Si-0.3Cr Alloys during High-Temperature Deformation
Authors: Zhou Meng , Li Yunzhang , Tang Shunlong , Ban Yijie , Zhang Yi , Gan Bin , Li Xu , Fu Lihua , Tian Baohong , Liu Yong , Volinsky Alex A.
Published: March 2023

Copper alloys with a combination of good electrical conductivity and mechanical properties are widely used in automotive electronics, large-scale integrated circuits, and other fields. In this study, a new type of Cu–Ni–Si alloy with added trace elements of Co and Cr was fabricated. Hot compression tests of this alloy at different temperatures and strain rates were conducted using a Gleeble-1500D simulator. Then, the microstructure transformation and precipitation behaviors of the Cu-1.1–Ni-0.7–Co-0.45–Si-0.3Cr alloy were studied during a hot deformation process. The results show that the hot deformation behavior of the Cu-1.1–Ni-0.7–Co-0.45–Si-0.3Cr alloy includes continuous dynamic recrystallization (CDRX) and discontinuous dynamic recrystallization (DDRX). The intensity of the texture in the microstructure is decreased, and the randomness of the texture in the microstructure is increased together with the recrystallization progress. The degree of recrystallization of the new Cu-1.1–Ni-0.7–Co-0.45–Si-0.3Cr alloy is increased when the hot deformation temperature rises. Additionally, the results indicate that there are two types of precipitates which are formed in the alloy during the hot deformation process. These two precipitates can pin dislocations and grain boundaries, and therefore, they significantly improve the hot compression resistance of the Cu-1.1–Ni-0.7–Co-0.45–Si-0.3Cr alloy.
Artificial Neural Network Model for Membrane Desalination: A Predictive and Optimization Study
Authors: Chan MieowKee , Shams Amin , Wang ChanChin , Lee PeiYi , Jahani Yousef , Mirbagheri Seyyed Ahmad
Published: March 2023

Desalination is a sustainable method to solve global water scarcity. A Response Surface Methodology (RSM) approach is widely applied to optimize the desalination performance, but further investigations with additional inputs are restricted. An Artificial neuron network (ANN) method is proposed to reconstruct the parameters and demonstrate multivariate analysis. Graphene oxide (GO) content, Polyhedral Oligomeric Silsesquioxane (POSS) content, operating pressure, and salinity were combined as input parameters for a four-dimensional regression analysis to predict the three responses: contact angle, salt rejection, and permeation flux. Average coefficient of determination (R2) values ranged between 0.918 and 0.959. A mathematical equation was derived to find global max and min values. Three objective functions and three-dimensional diagrams were applied to optimize effective cost conditions. It served as the database for the membranologists to decide the amount of GO to be used to fabricate membranes by considering the effects of operating conditions such as salinity and pressure to achieve the desired salt rejection, permeation flux, contact angle, and cost. The finding suggested that a membrane with 0.0063 wt% of GO, operated at 14.2 atm for a 5501 ppm salt solution, is the preferred optimal condition to achieve high salt rejection and permeation flux simultaneously.
A Novel Approach to Grain Shape Factor in 3D Hexagonal Cellular Automaton
Authors: Bao Lei , Shi Jun
Published: March 2023

Cellular automata (CA) modeling is a powerful and efficient tool for simulating the dynamic evolution of polycrystalline microstructures in modern materials and metallurgy studies, such as solidification, plastic deformation and recrystallization. We propose a novel model to calculate the shape factor of grains in three-dimensional hexagonal grid (3D-HEX) CA, which overcomes the disadvantages of 3D-HEX CA, such as complex algorithms and a long computation time. The shape factor is a quantitative measure of grain morphology based on the ratio of the surface area of the grain to its volume-equivalent-sphere and volume-equivalent-chain. It indicates how the shape of a grain or phase affects its mechanical properties, such as stiffness, deformation and fracture. Our model can easily calculate the shape factor for any grain by counting its surface cells and volume cells. We test our model on 1000 grains with different shapes (equiaxed, irregular and chain-like) by Monte Carlo (MC) methods. MC methods evaluate the validity of a calculation model by comparing the simulated outcomes with the observed or expected outcomes. The results show that our model can accurately describe the grain morphology and has a good comparability and generality.
Effect of Process Parameters on Arc Shape, Macroscopic Features, and Microhardness in Pulsed GMA–Additive Manufacturing
Authors: Zhang Gang , He Guanyu , Gu Yufen , Shi Yu
Published: March 2023

Gas metal arc welding-based additive manufacturing (GMA–AM) is a promising, low-cost approach to fabricate large-scale and complex geometry components using layer-by-layer deposition of metals. However, the low forming accuracy of GMA–AM still limits its one-off industrial application due to the strong and nonlinear interactions between arc–droplet transfer and molten pool. To fully understand the influential mechanism of this inherent interaction in the GMA–AM process to precisely control the part accuracy, the arc–droplet transfer behavior in the GMA–AM process with different current waveforms was firstly studied experimentally. The phenomena of the arc swing and the differing droplet transfer with the increase in deposited height were interpreted. The thermal force status of the molten pool and its balance boundary conditions were also theoretically analyzed. Finally, the microstructure and the hardness of the AM parts with different cooling times were tested and analyzed. The experimental results demonstrate that using the spray droplet transfer mode can generate a stable AM process under direct current application conditions, but it easily ends the AM process at the third or fourth layer deposition owing to excessive heat input. A more highly accurate deposition morphology can be obtained in one droplet per pulse mode under pulsed current application conditions, which also indicates that the AM process with a constant current welding supply is stabler and easily produces better deposition than the process with a constant voltage welding supply. With the increase in cooling time, the microstructure evolved from fine ferrite to equiaxed ferrite and to columnar ferrite combined with acicular ferrite with a lower proportion of pearlite in the vertical direction of the part, and the average hardness changed to ~168 HV (bottom), ~175 HV (middle), and ~250 HV (top). The analysis indicates that the heat accumulation of the molten pool is a critical factor that affects the deposition accuracy. To this end, a novel strategy that uses the heat accumulation to compensate for the energy formed in the molten pool is proposed to further reduce the arc heat input and weaken the heat accumulation, and its feasibility is discussed.
Some European Gentiana Species Are Used Traditionally to Cure Wounds: Bioactivity and Conservation Issues
Authors: Pasdaran Ardalan , Naychov Zheko , Batovska Daniela , Kerr Philip , Favre Adrien , Dimitrov Vladimir , Aneva Ina , Hamedi Azadeh , Kozuharova Ekaterina
Published: March 2023

Wound care will always be among the main tasks in all surgical specialties. Several medicinal plants have proven efficacy to cure wounds. Ethnobotanical research and ethnopharmacological research have virtually endless potential to find new lead compounds. The aim of this research review is to assess the potential of some Gentiana species as sources of promising active compounds to support wound healing. Gentians are among the most popular medicinal plants used in many countries for a wide spectrum of health conditions. Traditionally, those used to cure wounds are Gentiana lutea, G. punctata, G. asclepiadea, G. cruciata, G. oliverii, G. septemphida, and G. gelida. Candidate compounds with skin regeneration and wound-healing potential isolated from gentians are isogentisin, isoorientin, mangiferin, lupeol, pinoresinol, syringaresinol, eustomoside, and sweroside. Based on the rich source of traditional knowledge on the properties of gentians to cure various skin and soft tissue complications; only very few modern pharmacological studies have been performed to test this potential. Our review demonstrates that this field deserves further investigation. Many gentians are declining in number and have high IUCN conservation status, and cultivation and micropropagation methods are the only solution for the development of new drugs based on gentian extracts.
Is Laser Therapy an Adjuvant in the Treatment of Peri-Implant Mucositis? A Randomized Clinical Trial
Authors: Lazăr Luminița , Dakó Timea , Mureșan Izabella-Éva , Suciu Mircea , Maftei George-Alexandru , Tatarciuc Monica , Lazăr Ana-Petra
Published: March 2023

(1) Background: Early diagnosis and treatment of peri-implant mucositis may reduce inflammatory markers and halt the progression of the condition to peri-implantitis. Adjunctive laser treatment may have therapeutic benefits that are not yet well known. The aim of this study was to determine the advantages and limitations of laser therapy as an adjuvant in the treatment of peri-implant mucositis. (2) Methods: A total of 42 patients with at least 2 implants situated in different hemiarches were included in this study and divided into two groups: G1 (received laser therapy) and G2 (no laser therapy). Periodontal health status indices were recorded at the initial moment (T0), and all patients underwent non-surgical debridement therapy accompanied by oral hygiene training. In patients from group G1, one implant site received adjuvant laser therapy (subgroup IL), and the other one did not receive active laser light (IC). The plaque index (PI), probing pocket depth (PPD), and bleeding on probing (BOP) values recorded after 3 months (T1) and 6 months (T2) were analyzed and compared with those at T0. (3) Results: PI values considerably reduced at moment T1 and T2 for both G1 and G2 (p = 0.0031). PPD was also reduced, but the difference between the groups and the three recording moments was not statistically significant. Statistically significant differences were found when comparing the BOP values between G1 IL and G1 IC for T0/T1 (p = 0.0182) and T1/T2 (p < 0.0001), but there was no significant difference between G2 and G1 IL or G1 IC. (4) Conclusions: Laser therapy as an adjunct to conventional treatment of peri-implant mucositis leads to a statistically significant reduction in bleeding on probing at 3-month and 6-month re-evaluations. Moreover, it leads to an evident reduction in probing depth but with no statistical significance. These results should be interpreted with caution, and more in-depth research should be performed to create a complete laser therapy protocol for peri-implant mucositis.
Non-Aneurysmal Perimesencephalic Subarachnoid Hemorrhage: A Literature Review
Authors: Roman-Filip Iulian , Morosanu Valentin , Bajko Zoltan , Roman-Filip Corina , Balasa Rodica Ioana
Published: March 2023

Spontaneous non-aneurysmal subarachnoid haemorrhage (NAPMSAH) (addressing point 1) is a relatively rare occurrence in clinical settings as it is rarely misdiagnosed and usually involves a significantly better prognosis than the classical aneurysmal pattern. We hereby focused on a comprehensive analysis of this distinct pathological entity with the purpose of analysing possible pathophysiological entities, outcomes and treatment options involving this diagnosis with a focus on demographical, epidemiological and clinical data. The clinical setting includes focal neurological signs related to the anatomical structures, while computer tomography followed by tomographic angiography are the most common diagnosis tools, with a typical hyperdense lesion involving the midbrain, fourth ventricle and subthalamic areas without an angiographic correspondent, such as an aneurysmal pathology. Further investigations can also be used to highlight this diagnosis, such as interventional angiography or magnetic resonance imaging. Given the rarity of this condition and its relatively better prognosis, treatment options usually remain conservative. In the present review, the main characteristics of NAPMSAH are discussed.