bluuebunny/crossref_metadata_2025 huggingface dataset:
Involvement of Nrf2 Activation and NF-kB Pathway Inhibition in the Antioxidant and Anti-Inflammatory Effects of Hesperetin in Activated BV-2 Microglial Cells
Authors: Evans Jasmine A. , Mendonca Patricia , Soliman Karam F. A.
Published: July 2023

Alzheimer’s disease is a progressive neurodegenerative disorder leading to cognitive decline and memory loss. The incidence of this disease continues to increase due to the limited number of novel therapeutics that prevent or slow down its progression. Flavonoids have been investigated for their potential effects on cellular damage triggered by excessive reactive oxygen species (ROS) and neuroinflammatory conditions. This study investigated the effect of the flavonoid hesperetin on LPS-activated murine BV-2 microglial cells. Results show that hesperetin reduced nitric oxide levels and increased catalase, glutathione, and superoxide dismutase levels, suggesting its potential to reduce neuroinflammation and oxidative stress. Moreover, RT-PCR arrays showed that hesperetin modulated multiple genes that regulate oxidative stress. Hesperetin downregulated the mRNA expression of ERCC6, NOS2, and NCF1 and upregulated HMOX1 and GCLC. RT-PCR results showed that hesperetin-induced Nrf2 mRNA and protein expression in LPS-activated BV-2 microglial cells is involved in the transcription of several antioxidant genes, suggesting that hesperetin’s antioxidant effects may be exerted via the Keap1/Nrf2 signaling pathway. Furthermore, the data demonstrated that hesperetin reduced the gene expression of PD-L1, which is upregulated as an individual ages and during chronic inflammatory processes, and inhibited the expression of genes associated with NF-kB signaling activation, which is overactivated during chronic inflammation. It was concluded from this investigation that hesperetin may have therapeutic potential to prevent or slow down the progression of neurodegenerative diseases, such as Alzheimer's disease, by reducing chronic oxidative stress and modulating neuroinflammation.
The Genetic Basis of Probable REM Sleep Behavior Disorder in Parkinson’s Disease
Authors: Perez-Lloret Santiago , Chevalier Guenson , Bordet Sofia , Barbar Hanny , Capani Francisco , Udovin Lucas , Otero-Losada Matilde
Published: July 2023

Patients with Parkinson’s Disease (PD) experience REM sleep behavior disorder (RBD) more frequently than healthy controls. RBD is associated with torpid disease evolution. To test the hypothesis that differential genetic signatures might contribute to the torpid disease evolution in PD patients with RBD we compared the rate of genetic mutations in PD patients with or without probable RBD. Patients with a clinical diagnosis of PD in the Parkinson’s Progression Markers Initiative (PPMI) database entered the study. We excluded those with missing data, dementia, psychiatric conditions, or a diagnosis change over the first five years from the initial PD diagnosis. Probable RBD (pRBD) was confirmed by a REM Sleep Behavior Disorder Screening Questionnaire score > 5 points. Logistic regression and Machine Learning (ML) algorithms were used to relate Single Nucleotide Polymorphism (SNPs) in PD-related genes with pRBD. We included 330 PD patients fulfilling all inclusion and exclusion criteria. The final logistic multivariate model revealed that the following SNPs increased the risk of pRBD: GBA_N370S_rs76763715 (OR, 95% CI: 3.38, 1.45–7.93), SNCA_A53T_rs104893877 (8.21, 2.26–36.34), ANK2. CAMK2D_rs78738012 (2.12, 1.08–4.10), and ZNF184_rs9468199 (1.89, 1.08–3.33). Conversely, SNP COQ7. SYT17_rs11343 reduced pRBD risk (0.36, 0.15–0.78). The ML algorithms led to similar results. The predictive models were highly specific (95–99%) but lacked sensitivity (9–39%). We found a distinctive genetic signature for pRBD in PD. The high specificity and low sensitivity of the predictive models suggest that genetic mutations are necessary but not sufficient to develop pRBD in PD. Additional investigations are needed.
Other-Benefiting Lying Behavior in Preschool Children and Its Relation to Theory of Mind and Empathy
Authors: Zhang Xiaoyan , Wang Shenqinyi , Wang Ying , Zhao Qiuming , Shang Siyuan , Sai Liyang
Published: July 2023

The present study examined children’s lies to help others obtain benefits (other-benefiting lying) and its relation to theory of mind (ToM) and empathy among 3–5-year-old preschool children. One hundred nine children were recruited from preschools in China. A modified hide-and-seek paradigm was used to measure children’s other-benefiting lying behavior, a ToM scale was used to measure children’s ToM abilities, and an empathy scale was used to measure children’s empathy abilities. Results showed that children tended to tell more lies to help other to get benefits as age increased, and further analyses showed that this other-benefiting lying was related to children’s ToM component of false belief understanding and their cognitive empathy performance. These findings provide evidence that cognitive factors play important roles in children’s lying to help others.
College Student’s Academic Help-Seeking Behavior: A Systematic Literature Review
Authors: Li Ruihua , Che Hassan Norlizah , Saharuddin Norzihani
Published: July 2023

Seeking academic help has a positive impact on students’ ability to handle challenges, leading to improved academic success. As the academic landscape becomes more competitive, the importance of students seeking and using academic support is widely recognized for enhancing their learning experience and achievements. The main objective of this study is to review the prior literature that has examined the academic support provided to college students, addressing the knowledge and methods required in an academic help-seeking process. Based on a systematic literature review, this study’s data were gathered from a review of 55 documents from the 11 years between 2012 and 2022. The literature was then individually analyzed using the ATLAS.ti 22 programs. The analysis shows five central themes: (1) Defining student help-seeking; (2) Academic help-seeking and academic performance; (3) Resources of academic help-seeking; (4) Factors of academic help-seeking; (5) Academic Help Seeking Online. This study also identifies potential new directions for future research that could be useful to school administrators in developing policies to assist students with help-seeking behavior, which could have significant implications for the theoretical development and practical guidance of student help-seeking behavior.
Experimental Study on Axial Compressive Performance of Light-Steel Skeleton–Cement–Fly Ash Foam Wallboard
Authors: Liu Chengcong , Bai Yu , Jiang Xinli , Su Hexian
Published: July 2023

Foamed cement fly ash is a new type of lightweight construction material that can be combined with a light steel frame to form light-steel skeleton–cement–fly ash foam wallboard (LSSCFAFW). The research on the axial compressive performance of light steel and light concrete composite wallboard is relatively limited. Four pieces of LSSCFAFWs were manufactured, and the impact of stand column quantity and various filler parameters on the LSSCFAFW was investigated. The failure mode of the wallboard and the influence of different parameter variables on its axial compressive performance were obtained through experiments. Moreover, the test results indicated essentially the same damage patterns in terms of stand-column buckling, filler crushing, and self-tapping screw failure. The addition of polypropylene fiber to this wallboard can prevent filler from falling off. The axial compressive performance of the LSSCFAFW demonstrates a direct proportion with the number of columns and cement content, improving as the number of stand columns and the cement content increase. However, the addition of polypropylene fiber to the filler has a minimal effect on the axial compressive performance of this wallboard. Compared to the control group, increasing the number of stand columns, adding 0.4% polypropylene fibers, and increasing the cement dosage to 50% improved the ultimate bearing capacity of the wallboards by 12%, 8%, and 56% respectively. The result of this study can provide references for the research and application of light steel frame to form LSSCFAFW.
A Study of the Effects of Job Stress on the Psychosocial Safety Behavior of Construction Workers: The Mediating Role of Psychological Resilience
Authors: Lu Chenning , Yu Deming , Luo Qingyue , Xu Can
Published: July 2023

A large number of studies have been conducted to demonstrate that job stress negatively affects construction workers’ physiological safety behaviors, but there is a lack of research on the impact of psychosocial safety behaviors on construction workers, which is an important component of overall workplace safety. This study modeled the effects between three job stressors (the job itself, job insecurity, and family-work conflict) and psychosocial safety behavior sub-dimensions (psychosocial safety compliance and psychosocial safety participation), using psychological resilience as a mediating variable. Data were obtained from 304 construction workers in China. The results showed that there were positive and negative effects between the three job stressors, psychosocial safety behavior sub-dimensions, and psychological resilience. Psychological resilience was mediated differently across the three job stressors and psychosocial safety behavior sub-dimensions. This study reveals the mechanisms by which job stress affects the psychosocial safety behaviors of construction workers and provides more empirical evidence to unravel the relationships between various job stressors and psychosocial safety behavior sub-dimensions. In addition, this paper discusses measures to improve psychosocial safety behaviors based on the perspectives of job stressors and psychological resilience.
Kindness in Architecture: The Multispecies Co-Living and Co-Design
Authors: Saeidi Sareh , Anderson Matthew , Davidová Marie
Published: July 2023

The research’s main objective is to explore and encourage modes of architectural practice that can foster multispecies co-living to reduce biodiversity loss and increase the quality of life for both human and nonhuman inhabitants of architecture. This is achieved through conceptual discussions, comprehensive architectural case studies and work-based design explorations that support cross-species co-living in the context of Eastern Norway (Østlandet)—a geographical region of south-eastern Norway consisting of the counties Vestfold, Telemark, Viken, Oslo and Innlandet. A pluralistic method builds on analytical, critical and work-based explorative studies consisting of two parts: (a) historical and contemporary case studies in Norway that support modes of cross-species co-living and (b) design explorations by the second author investigating the operational potential of kindness in architecture. The notion of kindness in this research is built upon an understanding of the amalgam of concepts: solidarity, kinship and being kind, explained in the article’s introduction. The potential for designing with and for nonhumans to reinvigorate modes of co-living and support existing habitats is investigated, focusing on the ways three bird species relate to a specific building in Eastern Norway due to their habitat needs in the region: Cyanistes caeruleus, Eurasian blue tit (blåmeis in Norwegian); Passer montanus, Eurasian tree sparrow (pilfink in Norwegian); and Delichon urbicum, northern or common house martin (taksvale in Norwegian). The research contributes to ongoing discussions within architectural discourse regarding multispecies inhabitation and architecture’s role in the current biodiversity crisis and provides insight into both historical and contemporary/ongoing design solutions for multispecies co-living.
Research Progress on the Impact of Acoustic Waves on the Agglomeration of Oily Fine Particles in Industrial Oil Mist Environment
Authors: Li Dekang , Wang Xin , Li Tian , Yang Luying , Liu Yuhong , Wang Fei , Xu Yuwei , Yang Yang
Published: July 2023

Currently, undetectable damage to workers and factory products is caused by the large number of oily fine particles present in the industrial environment. Previous studies have shown that different intensities of sound waves can promote the coalescence of fine particles, and the combination of water vapor condensation can further enhance the effect of acoustic coalescence. However, the research on acoustic coalescence is not extensive enough at present, especially research on the mechanism of the coalescence and growth of oily fine particles under acoustic and water vapor complex fields, which is even less studied. This paper focused on summarizing domestic and foreign research results on the interaction mechanism of acoustic convergence on particles and the agglomeration and growth of particles under the action of acoustic convergence and combined water vapor condensation, so as to explore the technical path of using acoustic convergence and combined water vapor condensation to regulate the size of oily fine particles and improve the purification efficiency in industrial situations. This research has significant scientific significance and application value for industrial environmental control, pollutant emission control, and healthy environment construction.
Development of Ultra-High-Performance Silica Fume-Based Mortar Incorporating Graphene Nanoplatelets for 3-Dimensional Concrete Printing Application
Authors: Salah Husam A. , Mutalib Azrul A. , Kaish A. B. M. A. , Syamsir Agusril , Algaifi Hassan Amer
Published: July 2023

Although the use of 3D printing in civil engineering has grown in popularity, one of the primary challenges associated with it is the absence of steel bars inside the printed mortar. As a result, developing 3D printing mortar with ultra-high compressive, flexural, and tensile strengths is critical. In the present study, an ultra-high-performance mortar incorporating silica fume (SF) and graphene nanoplatelets (GNPs) was developed for 3D printing application. The concrete mixture added SF to the concrete mixture in the range between 0% and 20%, while GNPs were added as a partial replacement by cement weight from 0.5% to 2%. The flowability and the machinal properties of the proposed mortar, including compressive (CS), tensile (TS), and flexural strength (FS), were investigated and assessed. Microstructure analysis involving FESEM and EDX was also investigated and evaluated, while response surface methodology (RSM) was considered to predict and optimize the optimum value of GNPs and SF. Workability results show that the flowability is reduced when the amount of graphene increases. Based on the predicted and experimental results, ultra-high-strength mortar can be developed by including 1.5% of GNPs and 20% of SF, in which the CS jumped from 70.7 MPa to 133.3 MPa at the age of 28 days. The FS and TS were 20.66 MPa and 14.67 MPa compared to the control mix (9.75 MPa and 6.36 MPa), respectively. This favorable outcome was credited to the pozzolanic activity of SF and the effectiveness of GNPs in compacting the pores and bridging the cracks at the nanoscale level, which were verified by FE-SEM and EDX. In addition, the developed quadratic equations proved their accuracy in predicting and optimizing the mechanical properties with low error (less than 0.09) and high correlation (R2 > 0.97). It can be concluded that the current work is an important step forward in developing a 3D printing mortar. The lack of reinforcement in the printed mortar structure has been a considerable difficulty, and the SF and GNPs have increased the compressive, flexural, and tensile strengths of the mortar. Thus, these improvements will encourage the industry to utilize sustainable materials to produce more affordable housing.
Hybrid Photovoltaic Thermal Systems: Present and Future Feasibilities for Industrial and Building Applications
Authors: Samykano Mahendran
Published: July 2023

The growing demands of modern life, industrialization, and technological progress have significantly increased energy requirements. However, this heightened need for energy has raised concerns about its impact on the environment and the rising costs associated with it. Therefore, the engineering sector is actively seeking sustainable and cost-effective energy solutions. Among the promising innovations in solving the problem is the photovoltaic thermal system (PVT), which aims to capture electrical and thermal energy from solar radiation. Despite its potential, the application of PVT systems is currently limited due to the unpredictable nature of solar energy and the absence of efficient thermal energy storage capabilities. To address these challenges, researchers have explored the use of phase change materials and nano-improved phase change materials (NEPCMs) to optimize energy extraction from solar systems. By incorporating these materials, the PVT system can maximize energy utilization. This article provides a comprehensive overview of the potential applications of PVT techniques in both industrial and building settings. It also offers a detailed assessment of their commercial and environmental aspects. The research findings highlight several advantages of PVT systems, including reduced electricity consumption, efficient utilization of cooling and heating loads during off-peak periods, improved temperature stability, and enhanced thermal comfort. Furthermore, the integration of NEPCMs in PVT systems has demonstrated superior thermal performance, enabling 8.3% more heat energy storage during charging and 25.1% more heat energy release during discharging. Additionally, the implementation of solar-assisted combined heating and power systems showed the potential to prevent the emission of 911 tons of CO2 per year compared to conventional PV systems. These systems offer a promising pathway towards mitigating environmental impacts while meeting energy demands. Overall, this review article serves as a valuable resource for fellow researchers by providing detailed insights into the viability of PVT systems for various applications in the industrial and building sectors.
Effect of Web Perforations on the Web Buckling Resistance of 7075-T6 and AA-6086 High-Strength Aluminium Alloy C-Shaped Members under End-Two-Flange Loading Case
Authors: Sun Xiaoyong , Fu Jianhang , Sun Gang
Published: July 2023

Recently, new types of C-shaped members made from AA-6086 and 7075-T6 high-strength aluminium alloy have become more popular due to their high yield strength and lower cost. These members are often manufactured with pre-punched web perforations to simplify the installation of services, but this can reduce their strength. Also, such aluminium C-shaped members that contain perforated webs are vulnerable to web buckling failure, as aluminium alloy has a lower elastic modulus compared to steel. However, this influence has not been investigated for high-strength aluminium alloy sections to date. An extensive numerical investigation was undertaken to examine the effect of web perforations on the web buckling resistance of high-strength aluminium alloy C-shaped members under an end-two-flange (ETF) loading case, and this study focused on two types of aluminium alloys, namely 7075-T6 and AA-6086. To achieve this, a nonlinear finite element (FE) model was developed and validated using the test data in the literature. The material properties used in the FE models were obtained from the relevant literature. A parametric investigation was carried out, consisting of a total of 1458 models. In this investigation, a number of variables were examined, including the web hole size, web hole location, bearing length, fillet radius and aluminium alloy grades. The results showed that increasing the a/h ratio from 0.1 to 0.5 resulted in a decrease of 9.7% and 9.3% in the web buckling resistance for the 7075-T6 aluminium and AA-6086 aluminium, respectively. When the length of the bearing plates (N) varied from 100 mm to 200 mm, the web buckling resistance experienced an average increase of 61.7% for the 7075-T6 aluminium and 54.1% for the AA-6086 aluminium. Also, the web buckling resistance increased by 6.2% for the 7075-T6 aluminium alloy, while the strength increased by 4.0% for the AA-6086 aluminium alloy when the x/h ratio increased from 0.1 to 0.5. The numerical data generated from the parametric study were used to assess the accuracy and suitability of the latest design recommendations, and it was found that the design rules presented in the previous literature cannot provide reliable and safe predictions for estimating the web buckling resistance of aluminium C-shaped members that contain perforated webs under an ETF loading case. Finally, new design formulas were proposed in the form of strength reduction factors. A reliability assessment was then undertaken, and the results of this analysis indicated that the proposed design formulas can accurately predict the web buckling resistance of such members with perforated webs.
Data-Driven Smart Avatar for Thermal Comfort Evaluation in Chile
Authors: Hormazábal Nina , Franco Patricia , Urtubia David , Ahmed Mohamed A.
Published: July 2023

This work proposes a data-driven decision-making approach to develop a smart avatar that allows for evaluating the thermal comfort experienced by a user in Chile. The ANSI/ASHRAE 55-2020 standard is the basis for the predicted mean vote (PMV) comfort index, which is calculated by a random forest (RF) regressor using temperature, humidity, airspeed, metabolic rate, and clothing as inputs. To generate data from four cities with different climates, a 3.0 m × 3.0 m × 2.4 m shoe box with two adiabatic walls was modeled in Rhino and evaluated using Grasshopper’s ClimateStudio plugin based on Energy Plus+. Long short-term memory (LSTM) was used to forecast the PMV for the next hour and inform decisions. A rule-based decision-making algorithm was implemented to emulate user behavior, which included turning the air conditioner (AC) or heater ON/OFF, recommendations such as dressing/undressing, opening/closing the window, and doing nothing in the case of neutral thermal comfort. The RF regressor achieved a root mean square error (RMSE) of 0.54 and a mean absolute error (MAE) of 0.28, while the LSTM had an RMSE of 0.051 and an MAE of 0.025. The proposed system was successful in saving energy in Calama (31.2%), Valparaiso (69.2%), and the southern cities of Puerto Montt and Punta Arena (23.6%), despite the increased energy consumption needed to maintain thermal comfort.
Predictive Model of Temperature Regimes of a Concrete Gravity Dam during Construction: Reducing Cracking Risks
Authors: Aniskin Nikolai Alekseevich , Nguyen Trong Chuc
Published: July 2023

In consideration of the mild climatic conditions of North Vietnam with average monthly air temperatures ranging from 15 °C in winter to 26.5 °C, this study analyzes the regulation of the temperature regime and thermally stressed state of a concrete gravity dam made of rolled concrete. Despite the favorable weather conditions, there remains a risk of thermal cracking, necessitating the presentation of crack-formation models from different countries to assess and mitigate the risk of cracking through the adjustment of construction conditions. The study has developed a predictive model for the temperature regime and thermally stressed state of a layer-by-layer concrete mass under the given construction conditions using the factor-analysis method. Regression equations were then derived from the factorial experiment to quantify the responses of the maximum temperature and maximum stress in the concrete mass. The numerical finite-element method using the Midas Civil software package was employed to calculate the temperature regime and thermally stressed state of the concrete mass. To validate the mathematical predictive model, it was tested on the Ban Lai gravity dam in North Vietnam. The dam, which was constructed from rolled concrete and stands 56 m tall, was selected as the object in this practical example. The results obtained from applying the predictive model were compared to the results obtained from numerical calculations of the dam under construction, as well as the findings from field observations. These results were found to be in good agreement, indicating the effectiveness of the predictive model. Furthermore, an evaluation of the potential for temperature cracking of the concrete during the construction period was conducted.
The Bivalent Bromodomain Inhibitor MT-1 Inhibits Prostate Cancer Growth
Authors: Shukla Sanjeev , Riveros Carlos , Al-Toubat Mohammed , Chardon-Robles Jonathan , Osumi Teruko , Serrano Samuel , Kase Adam M. , Petit Joachim L. , Meurice Nathalie , Gleba Justyna , Copland John A. , Chauhan Jay , Fletcher Steven , Balaji K. C.
Published: July 2023

Bromodomains (BD) are epigenetic readers of histone acetylation involved in chromatin remodeling and transcriptional regulation of several genes including protooncogene cellular myelocytomatosis (c-Myc). c-Myc is difficult to target directly by agents due to its disordered alpha helical protein structure and predominant nuclear localization. The epigenetic targeting of c-Myc by BD inhibitors is an attractive therapeutic strategy for prostate cancer (PC) associated with increased c-Myc upregulation with advancing disease. MT-1 is a bivalent BD inhibitor that is 100-fold more potent than the first-in-class BD inhibitor JQ1. MT-1 decreased cell viability and causes cell cycle arrest in G0/G1 phase in castration-sensitive and resistant PC cell lines in a dose-dependent fashion. The inhibition of c-Myc function by MT-1 was molecularly corroborated by the de-repression of Protein Kinase D1 (PrKD) and increased phosphorylation of PrKD substrate proteins: threonine 120, serine 11, and serine 216 amino acid residues in β-Catenin, snail, and cell division cycle 25c (CDC25c) proteins, respectively. The treatment of 3D cell cultures derived from three unique clinically annotated heavily pretreated patient-derived PC xenografts (PDX) mice models with increasing doses of MT-1 demonstrated the lowest IC50 in tumors with c-Myc amplification and clinically resistant to Docetaxel, Cabazitaxel, Abiraterone, and Enzalutamide. An intraperitoneal injection of either MT-1 or in combination with 3jc48-3, an inhibitor of obligate heterodimerization with MYC-associated protein X (MAX), in mice implanted with orthotopic PC PDX, decreased tumor growth. This is the first pre-clinical study demonstrating potential utility of MT-1 in the treatment of PC with c-Myc dysregulation.
Intraoperative Contrast-Enhanced Ultrasonography (Io-CEUS) in Minimally Invasive Thoracic Surgery for Characterization of Pulmonary Tumours: A Clinical Feasibility Study
Authors: Schauer Martin Ignaz , Jung Ernst-Michael , Platz Batista da Silva Natascha , Akers Michael , Loch Elena , Markowiak Till , Piler Tomas , Larisch Christopher , Neu Reiner , Stroszczynski Christian , Hofmann Hans-Stefan , Ried Michael
Published: July 2023

Background: The intraoperative detection of solitary pulmonary nodules (SPNs) continues to be a major challenge, especially in minimally invasive video-assisted thoracic surgery (VATS). The location, size, and intraoperative frozen section result of SPNs are decisive regarding the extent of lung resection. This feasibility study investigates the technical applicability of intraoperative contrast-enhanced ultrasonography (Io-CEUS) in minimally invasive thoracic surgery. Methods: In this prospective, monocentric clinical feasibility study, n = 30 patients who underwent Io-CEUS during elective minimally invasive lung resection for SPNs between October 2021 and February 2023. The primary endpoint was the technical feasibility of Io-CEUS during VATS. Secondary endpoints were defined as the detection and characterization of SPNs. Results: In all patients (female, n = 13; mean age, 63 ± 8.6 years) Io-CEUS could be performed without problems during VATS. All SPNs were detected by Io-CEUS (100%). SPNs had a mean size of 2.2 cm (0.5–4.5 cm) and a mean distance to the lung surface of 2.0 cm (0–6.4 cm). B-mode, colour-coded Doppler sonography, and contrast-enhanced ultrasound were used to characterize all tumours intraoperatively. Significant differences were found, especially in vascularization as well as in contrast agent behaviour, depending on the tumour entity. After successful lung resection, a pathologic examination confirmed the presence of lung carcinomas (n = 17), lung metastases (n = 10), and benign lung tumours (n = 3). Conclusions: The technical feasibility of Io-CEUS was confirmed in VATS before resection regarding the detection of suspicious SPNs. In particular, the use of Doppler sonography and contrast agent kinetics revealed intraoperative specific aspects depending on the tumour entity. Further studies on Io-CEUS and the application of an endoscopic probe for VATS will follow.
A Theranostic Approach to Imaging and Treating Melanoma with 203Pb/212Pb-Labeled Antibody Targeting Melanin
Authors: Jiao Rubin , Allen Kevin J. H. , Malo Mackenzie E. , Yilmaz Orhan , Wilson John , Nelson Bryce J. B. , Wuest Frank , Dadachova Ekaterina
Published: July 2023

Metastatic melanoma is a deadly disease that claims thousands of lives each year despite the introduction of several immunotherapeutic agents into the clinic over the past decade, inspiring the development of novel therapeutics and the exploration of combination therapies. Our investigations target melanin pigment with melanin-specific radiolabeled antibodies as a strategy to treat metastatic melanoma. In this study, a theranostic approach was applied by first labeling a chimeric antibody targeting melanin, c8C3, with the SPECT radionuclide 203Pb for microSPECT/CT imaging of C57Bl6 mice bearing B16-F10 melanoma tumors. Imaging was followed by radioimmunotherapy (RIT), whereby the c8C3 antibody is radiolabeled with a 212Pb/212Bi “in vivo generator”, which emits cytotoxic alpha particles. Using microSPECT/CT, we collected sequential images of B16-F10 murine tumors to investigate antibody biodistribution. Treatment with the 212Pb/212Bi-labeled c8C3 antibody demonstrated a dose-response in tumor growth rate in the 5–10 µCi dose range when compared to the untreated and radiolabeled control antibody and a significant prolongation in survival. No hematologic or systemic toxicity of the treatment was observed. However, administration of higher doses resulted in a biphasic tumor dose response, with the efficacy of treatment decreasing when the administered doses exceeded 10 µCi. These results underline the need for more pre-clinical investigation of targeting melanin with 212Pb-labeled antibodies before the clinical utility of such an approach can be assessed.
Primary Total Prostate Cryoablation for Localized High-Risk Prostate Cancer: 10-Year Outcomes and Nomograms
Authors: Chen Chung-Hsin , Tsai Chung-You , Pu Yeong-Shiau
Published: July 2023

The role of prostate cryoablation was still uncertain for patients with high-risk prostate cancer (PC). This study was designed to investigate 10-year disease-free survival and establish a nomogram in localized high-risk PC patients. Between October 2008 and December 2020, 191 patients with high-risk PC who received primary total prostate cryoablation (PTPC) were enrolled. The primary endpoint was biochemical recurrence (BCR), defined using Phoenix criteria. The performance of pre-operative and peri-operative nomograms was determined using the Harrell concordance index (C-index). Among the cohort, the median age and PSA levels at diagnosis were 71 years and 12.3 ng/mL, respectively. Gleason sum 8–10, stage ≥ T3a, and PSA > 20 ng/mL were noted in 27.2%, 74.4%, and 26.2% of patients, respectively. During the median follow-up duration of 120.4 months, BCR-free rates at 1, 3, 5, and 10 years were 92.6%, 76.6%, 66.7%, and 50.8%, respectively. The metastasis-free, cancer-specific, and overall survival rates were 89.5%, 97.4%, and 90.5% at 10 years, respectively. The variables in the pre-operative nomogram for BCR contained PSA at diagnosis, clinical stage, and Gleason score (C-index: 0.73, 95% CI, 0.67–0.79). The variables in the peri-operative nomogram for BCR included PSA at diagnosis, Gleason score, number of cryoprobes used, and PSA nadir (C-index: 0.83, 95% CI, 0.78–0.88). In conclusion, total prostate cryoablation appears to be an effective treatment option for selected men with high-risk PC. A pre-operative nomogram can help select patients suitable for cryoablation. A peri-operative nomogram signifies the importance of the ample use of cryoprobes and helps identify patients who may need early salvage treatment.
Anticancer Potential of the Cyclolinopeptides
Authors: Fojnica Adnan , Gromilic Zehra , Vranic Semir , Murkovic Michael
Published: July 2023

Novel therapeutic agents to combat cancer is an active area of research, as current treatment options have limitations in efficacy and tolerability. One of these therapeutic agents in our immediate environment is cyclolinopeptides (CLPs). CLPs have several advantages that make them suitable for daily consumption and potential therapeutics in cancer research. They are natural compounds, having high specificity, low toxicity, low cost, and an overall simple extraction process. Over the years, numerous in vitro studies in cancer cells demonstrated CLPs to possess anti-proliferative, apoptotic, and anti-angiogenic effects, as well as the ability to induce cell cycle arrest and inhibit cancer cell growth in various cancer types, including breast cancer, gastric cancer, and melanoma. This paper provides an overview of the significance and potential of CLPs as therapeutic agents, emphasizing their promising role in cancer treatment based on different cancer cell lines. The mechanism of action of CLPs in cancer cells is multifaceted. It involves the modulation of multiple signaling pathways, including inhibition of protein kinases, modulation of apoptosis-related proteins, and regulation of oxidative stress and inflammation.
Relationships among Inflammatory Biomarkers and Objectively Assessed Physical Activity and Sleep during and after Chemotherapy for Gynecologic Malignancies
Authors: Tometich Danielle B. , Hoogland Aasha I. , Small Brent J. , Janelsins Michelle C. , Bryant Crystal , Rodriguez Yvelise , Gonzalez Brian D. , Li Xiaoyin , Bulls Hailey W. , James Brian W. , Arboleda Bianca , Colon-Echevarria Claudia , Townsend Mary K. , Tworoger Shelley S. , Rodriguez Paulo , Oswald Laura B. , Bower Julienne E. , Apte Sachin M. , Wenham Robert M. , Chon Hye Sook , Shahzad Mian M. , Jim Heather S. L.
Published: July 2023

Little is known regarding associations between inflammatory biomarkers and objectively measured physical activity and sleep during and after chemotherapy for gynecologic cancer; thus, we conducted a longitudinal study to address this gap. Women with gynecologic cancer (patients) and non-cancer controls (controls) completed assessments before chemotherapy cycles 1, 3, and 6 (controls assessed contemporaneously), as well as at 6- and 12-month follow-ups. Physical activity and sleep were measured using wrist-worn actigraphs and sleep diaries, and blood was drawn to quantify circulating levels of inflammatory markers. Linear and quadratic random-effects mixed models and random-effects fluctuation mixed models were used to examine physical activity and sleep over time, as well as the associations with inflammatory biomarkers. On average, patients (n = 97) and controls (n = 104) were 62 and 58 years old, respectively. Compared to controls, patients were less active, more sedentary, had more time awake after sleep onset, and had lower sleep efficiency (p-values < 0.05). Across groups, higher levels of TNF-α were associated with more sedentary time and less efficient sleep (p-values ≤ 0.05). Higher levels of IL-1β, TNF-α, and IL-6 were associated with lower levels of light physical activity (p-values < 0.05). Associations between inflammatory biomarkers, physical activity, and sleep did not differ between patients and controls. Given these results, we speculate that inflammation may contribute to less physical activity and more sleep problems that persist even 12 months after completing chemotherapy.
The Neurodevelopmental and Molecular Landscape of Medulloblastoma Subgroups: Current Targets and the Potential for Combined Therapies
Authors: Slika Hasan , Alimonti Paolo , Raj Divyaansh , Caraway Chad , Alomari Safwan , Jackson Eric M. , Tyler Betty
Published: July 2023

Medulloblastoma is the most common malignant pediatric brain tumor and is associated with significant morbidity and mortality in the pediatric population. Despite the use of multiple therapeutic approaches consisting of surgical resection, craniospinal irradiation, and multiagent chemotherapy, the prognosis of many patients with medulloblastoma remains dismal. Additionally, the high doses of radiation and the chemotherapeutic agents used are associated with significant short- and long-term complications and adverse effects, most notably neurocognitive delay. Hence, there is an urgent need for the development and clinical integration of targeted treatment regimens with greater efficacy and superior safety profiles. Since the adoption of the molecular-based classification of medulloblastoma into wingless (WNT) activated, sonic hedgehog (SHH) activated, group 3, and group 4, research efforts have been directed towards unraveling the genetic, epigenetic, transcriptomic, and proteomic profiles of each subtype. This review aims to delineate the progress that has been made in characterizing the neurodevelopmental and molecular features of each medulloblastoma subtype. It further delves into the implications that these characteristics have on the development of subgroup-specific targeted therapeutic agents. Furthermore, it highlights potential future avenues for combining multiple agents or strategies in order to obtain augmented effects and evade the development of treatment resistance in tumors.
Functional In Vivo Screening Identifies microRNAs Regulating Metastatic Dissemination of Prostate Cancer Cells to Bone Marrow
Authors: Ivkovic Tina Catela , Cornella Helena , Voss Gjendine , Ku Anson , Persson Margareta , Rigo Robert , Gruvberger-Saal Sofia K. , Saal Lao H. , Ceder Yvonne
Published: July 2023

Distant metastasis is the major cause of cancer-related deaths in men with prostate cancer (PCa). An in vivo functional screen was used to identify microRNAs (miRNAs) regulating metastatic dissemination of PCa cells. PC3 cells transduced with pooled miRZiP™ lentivirus library (anti-miRNAs) were injected intraprostatic to 13 NSG mice followed by targeted barcode/anti-miR sequencing. PCa cells in the primary tumours showed a homogenous pattern of anti-miRNAs, but different anti-miRNAs were enriched in liver, lung, and bone marrow, with anti-miR-379 highly enriched in the latter. The bone metastasis-promoting phenotype induced by decreased miR-379 levels was also confirmed in a less metastatic PCa cell line, 22Rv1, where all mice injected intracardially with anti-miR-379-22Rv1 cells developed bone metastases. The levels of miR-379 were found to be lower in bone metastases compared to primary tumours and non-cancerous prostatic tissue in a patient cohort. In vitro functional studies suggested that the mechanism of action was that reduced levels of miR-379 gave an increased colony formation capacity in conditions mimicking the bone microenvironment. In conclusion, our data suggest that specific miRNAs affect the establishment of primary tumours and metastatic dissemination, with a loss of miR-379 promoting metastases in bone.
Cancer-Associated Thrombosis on Bevacizumab: Risk of Recurrence and Bleeding When Bevacizumab Is Stopped or Continued
Authors: Mayenga Marie , Falvo Nicolas , Mahé Isabelle , Jannot Anne-Sophie , Gazeau Benoit , Meyer Guy , Gendron Nicolas , Sanchez Olivier , Djennaoui Sadji , Planquette Benjamin
Published: July 2023

Cancer-associated thrombosis (CAT) is a common complication during cancer, with complex management due to an increased risk of both recurrence and bleeding. Bevacizumab is an effective anti-angiogenic treatment but increases the risk of bleeding and potentially the risk of venous thromboembolism (VTE). The aim of this study was to evaluate the efficacy and safety of anticoagulant therapy in patients with CAT receiving bevacizumab, according to the continuation or discontinuation of bevacizumab. In a retrospective multicenter study, patients receiving anticoagulant for CAT occurring under bevacizumab therapy were included. The primary endpoint combined recurrent VTE and/or major or clinically relevant non-major bleeding. Among the 162 patients included, bevacizumab was discontinued in 70 (43.2%) patients and continued in 92 (56.8%) patients. After a median follow-up of 318 days, 21 (30.0%) patients in the discontinuation group experienced VTE recurrence or major or clinically relevant non-major bleeding, compared to 27 (29.3%) in the continuation group. The analysis of survival following the first event showed no significant difference between the groups in uni- or multivariate analysis (p = 0.19). The primary endpoint was not influenced by the duration of bevacizumab exposure. These results suggest that the efficacy and safety of anticoagulant therapy in patients with CAT receiving bevacizumab is not modified regardless of whether bevacizumab is continued or discontinued.
Mapping the Potential of Microfluidics in Early Diagnosis and Personalized Treatment of Head and Neck Cancers
Authors: Pillai Sangeeth , Kwan Jan C. , Yaziji Fares , Yu Hanwen , Tran Simon D.
Published: July 2023

Head and neck cancers (HNCs) account for ~4% of all cancers in North America and encompass cancers affecting the oral cavity, pharynx, larynx, sinuses, nasal cavity, and salivary glands. The anatomical complexity of the head and neck region, characterized by highly perfused and innervated structures, presents challenges in the early diagnosis and treatment of these cancers. The utilization of sub-microliter volumes and the unique phenomenon associated with microscale fluid dynamics have facilitated the development of microfluidic platforms for studying complex biological systems. The advent of on-chip microfluidics has significantly impacted the diagnosis and treatment strategies of HNC. Sensor-based microfluidics and point-of-care devices have improved the detection and monitoring of cancer biomarkers using biological specimens like saliva, urine, blood, and serum. Additionally, tumor-on-a-chip platforms have allowed the creation of patient-specific cancer models on a chip, enabling the development of personalized treatments through high-throughput screening of drugs. In this review, we first focus on how microfluidics enable the development of an enhanced, functional drug screening process for targeted treatment in HNCs. We then discuss current advances in microfluidic platforms for biomarker sensing and early detection, followed by on-chip modeling of HNC to evaluate treatment response. Finally, we address the practical challenges that hinder the clinical translation of these microfluidic advances.
Neodymium-Doped Zinc Oxide Nanoparticles Catalytic Cathode for Enhanced Efficiency of Microbial Desalination Cells
Authors: Chauhan Sunil , Rai Shweta , Pandit Soumya , Roy Arpita , Gacem Amel , El-Hiti Gamal A. , Yadav Krishna Kumar , Ravindran Balasubramani , Cheon Ji-Kwang , Jeon Byong-Hun
Published: July 2023

The Microbial Desalination Cell is a novel method for desalinating water that also generates energy via substrate oxidation. The MDC comprises three chambers: the anode chamber, the desalination chamber, and the cathode chamber. The fundamental problem with the technology is that it generates very little power during the oxygen reduction reaction (ORR). One solution to this issue is to use a highly active cathode catalyst, which effectively increases the ORR rate. Neodymium-doped ZnO nanoparticles were produced and employed as a cathode catalyst in the three-chambered MDC1 to improve performance. Zn1−xNdxO nanocrystalline samples containing x = 0.0, 0.03, 0.6, and 0.10 were synthesized efficiently through the cost-efficient sol-gel method. Transmission electron microscopy (TEM) and X-ray diffraction techniques revealed the nanocrystalline nature and the phase purity of the Zn1−xNdxO samples. The structural properties of ZnO nanostructured materials were elucidated by Rietveld refinement of the XRD patterns, which showed displacement of Zn and O ions and revealed changes in the electron density around the Zn-O bond with Nd substitution. The local features of light emission from Zn1−xNdxO samples have been studied with photoluminescence. The UV and green-yellow emissions originate from the exciton transition and the transition between the Nd3+ deep level, oxygen vacancy and interstitial oxygen. The results were compared to MDC-2, which did not have a catalyst on the cathode. Both MDCs were tested using a saline water solution containing 15 g/L of NaCl to measure their desalination performance. The better reduction kinetics was confirmed by cyclic voltammetry of the MDC-1 cathode. MDC-1 had a higher desalination efficiency (77.02% ± 2.0%) due to the presence of an Nd-doped ZnO catalyst than MDC-2 (59.3% ± 8.3%). MDC-1’s maximum power density of 3.65 W/m3 was 2.78 times greater than MDC-2’s (0.78 W/m3). Furthermore, the coulombic efficiency of MDC-1 was found to be (8.8 ± 0.3%), which was much higher than that of MDC-2 (4.56 ± 0.2%). As a result, the Nd-doped ZnO-based catalyst developed in this study can potentially improve ORR in MDC cathodes, enabling them to generate more power.
The Role of Fe in Ni-Fe/TiO2 Catalysts for the Dry Reforming of Methane
Authors: Dhillon Gagandeep Singh , Cao Guoqiang , Yi Nan
Published: July 2023

A series of nickel- and iron-modified titanium dioxide (Ni-Fe/TiO2) are studied for the dry reforming of methane (DRM) at 550 °C. Temperature-programmed surface reactions using CH4 and CO2 as probe molecules, as well as activity results, confirmed that both CO2 and CH4 conversion decreased with the addition of Fe. The XPS results obtained from reduced and used catalysts suggested changes in the surface nickel and iron species. Characterizations, particularly thermogravimetric analysis (TGA) and Raman spectroscopy over used catalysts, revealed that the addition of Fe can greatly inhibit the coke formation. In situ DRIFTS further identified that the addition of Fe favored the formation of carbonate species, which can facilitate the removal of coke deposited on the surface.
Effect of the Ni-to-CaO Ratio on Integrated CO2 Capture and Direct Methanation
Authors: Woo Jin-Hyeok , Jo Seongbin , Kim Ju-Eon , Kim Tae-Young , Son Han-Dong , Ryu Ho-Jung , Hwang Byungwook , Kim Jae-Chang , Lee Soo-Chool , Gilliard-AbdulAziz Kandis Leslie
Published: July 2023

Direct methanation in an integrated CO2 capture and utilization system has recently gained considerable attention as a promising approach owing to its simplified process and lower requirement of total thermal energy as compared to conventional CO2 capture and utilization techniques. This study formulated macroporous structured Ni/CaO catal-sorbents by controlling the Ni-to-CaO ratio. The influence of this ratio on the CO2 capture (capacity and kinetics) and direct methanation performances (productivity and kinetics) was evaluated at 500 °C. CO2 capture combined with direct methanation experiments revealed that 10Ni/CaO exhibited the best CO2 capture capacity, kinetics, and CH4 productivity with the thermal stability of Ni and CaO species.