bluuebunny/crossref_metadata_2025 huggingface dataset:
Security and Privacy in Connected Vehicle Cyber Physical System Using Zero Knowledge Succinct Non Interactive Argument of Knowledge over Blockchain
Authors: Khan Rabia , Mehmood Amjad , Iqbal Zeeshan , Maple Carsten , Epiphaniou Gregory
Published: February 2023

Security has been the most widely researched topic, particularly within IoT, and has been considered as the major hurdle in the adoption of different applications of IoT. When it comes to IoV, security is considered as the most inevitable component to ensure a safe and smooth driving experience. CAV is the new era of transportation, integrating intelligence and self-driving capabilities within vehicles and that requires strong security measures to ensure safety. Security alone is not enough. Instead, a complete package including privacy of the vehicles and passengers needs to be added in addition to secure communication. This is because CAVs are under continuous cyber threats and attacks and the most important among them is the DDoS, where a remote attacker can hijack/launch attacks on vehicles remotely. Single point of failure attacks target the centralized trusted body in order to mislead the connected vehicles for personal gains. In this paper, the authors have proposed a secure communication system for CAVs using blockchain, which also ensures the privacy of the vehicle/people. The paper highlights the major components of the proposed system, and its performance is evaluated to check its efficiency against DDoS and Eclipse attacks. The unlinkability and anonymity of the vehicles have been ensured using the zk-SNAKR protocol over Blockchain.
Enhancement of Underwater Images with Retinex Transmission Map and Adaptive Color Correction
Authors: Chen Erkang , Ye Tian , Chen Qianru , Huang Bin , Hu Yendo
Published: February 2023

Underwater images often suffer from low contrast, low visibility, and color deviation. In this work, we propose a hybrid underwater enhancement method consisting of addressing an inverse problem with novel Retinex transmission map estimation and adaptive color correction. Retinex transmission map estimation does not rely on channel priors and aims to decouple from the unknown background light, thus avoiding error accumulation problem. To this end, global white balance is performed before estimating the transmission map using multi-scale Retinex. To further improve the enhancement performance, we design the adaptive color correction which cleverly chooses between two color correction procedures and prevents channel stretching imbalance. Quantitative and qualitative comparisons of our method and state-of-the-art underwater image enhancement methods demonstrate superiority of the proposed method. It achieves the best performance in terms of full-reference image quality assessment. In addition, it also achieves superior performance in the non-reference evaluation.
The Influence of Calcium Ions on the Electrotransfer Efficiency of Plasmid DNA and Cell Viability
Authors: Palepšienė Rūta , Maciulevičius Martynas , Ruzgys Paulius , Jakštys Baltramiejus , Šatkauskas Saulius
Published: February 2023

Gene electrotransfer (GET) is recognized as a promising technique for the development of an efficient tool for gene therapy. Such a therapy would have applications in the treatment of a variety of genetic diseases, including cancer. However, despite its wide applicability, the technique is limited by the lack of understanding of the fundamental mechanism of electroporation as well as other important factors that directly or indirectly influence its success rate. In the current study, we analyzed the impact of low concentrations (0–1 mM) of Ca2+ on the process of DNA electrotransfer using flow cytometry. The results revealed that the presence of a CaCl2 concentration as low as 0.25 mM decreased the efficiency of GET by ~1.5-fold and cell viability decreased by ~2–3-fold. In addition, we determined that the observed phenomenon of the decrease in pDNA electrotransfer due to the influence of Ca2+ was not the consequence of cell death but rather should be attributed to secondary mechanisms. The data presented in this study provide an insight into the importance of Ca2+ in the process of gene electrotransfer that may be directly applicable to in vivo settings.
Differential Strategies of Continuous Agri-Product Supply Chain Considering Consumer Perception of Eco-Quality
Authors: Chen Shan , Duan Yuelin , Su Jiafu , Tuo Junbo
Published: February 2023

Considering the influence of the consumers’ perception of eco-quality (CPQ) on the dynamic strategies of the continuous agri-product supply chain, the paper examines a two-stage agri-product supply chain composed of a supplier and a retailer, where the supplier invests in eco-quality improvement and the retailer invests in advertising. Taking the CPQ, eco-quality and goodwill as ternary state variables, the paper formulates joint decision-making models of a continuous agri-product supply chain based on differential game theory. The paper has analyzed equilibrium strategies in decentralized and centralized scenarios, respectively, and further developed an advertising–eco-quality investment cost-sharing contract to coordinate the supply chain. Finally, comparative and numerical analyses have been conducted. The analyses results reveal that consumers’ perceptions of eco-quality and their goodwill preference towards an agri-product encourage the supplier and retailer to improve the eco-quality of the agri-product and the level of advertising. Indeed, the greater the impact of goodwill on demand, the higher level of the supplier’s eco-quality investment and the retailer’s advertising effort, and the higher the profits of the supply chain. The paper also finds that the proposed cost-sharing contract can achieve a Pareto improvement in the continuous agri-product supply chain system. Furthermore, the higher the consumer goodwill preference, the more motivated suppliers and retailers are to cooperate.
An Integrated BWM-TOPSIS-I Approach to Determine the Ranking of Alternatives and Application of Sustainability Analysis of Renewable Energy
Authors: Alshamrani Ahmad , Majumder Priyanka , Das Amrit , Hezam Ibrahim M. , Božanić Darko
Published: February 2023

The purpose of this paper is to identify the most significant alternatives of renewable energy sustainability using a hybrid decision-making model of multiple criteria. Sustainable energy sources cannot run out and can be used for an indefinite period of time. In addition to meeting our energy needs, sustainable energy does not need to be renewed or replenished, nor does it pose any threat of being wrong or running out. Our energy demands can only be met by renewable energy. The bestworst methodand technique for order preference by similarities to ideal solution-I processes have proposed a hybrid model named the bestworst method—technique for order preference by similarities to ideal solution-I, for this purpose. This study uses comparative analysis and sensitivity analysis to determine the results of the proposed study.
Functional Prediction of Microbial Communities in Sediment Microbial Fuel Cells
Authors: Kuo Jimmy , Liu Daniel , Lin Chorng-Horng
Published: February 2023

Sediment microbial fuel cells (MFCs) were developed in which the complex substrates present in the sediment could be oxidized by microbes for electron production. In this study, the functional prediction of microbial communities of anode-associated soils in sediment MFCs was investigated based on 16S rRNA genes. Four computational approaches, including BugBase, Functional Annotation of Prokaryotic Taxa (FAPROTAX), the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt2), and Tax4Fun2, were applied. A total of 67, 9, 37, and 38 functional features were statistically significant. Among these functional groups, the function related to the generation of precursor metabolites and energy was the only one included in all four computational methods, and the sum total of the proportion was 93.54%. The metabolism of cofactor, carrier, and vitamin biosynthesis was included in the three methods, and the sum total of the proportion was 29.94%. The results suggested that the microbial communities usually contribute to energy metabolism, or the metabolism of cofactor, carrier, and vitamin biosynthesis might reveal the functional status in the anode of sediment MFCs.
Exploring the Effects of EEG-Based Alpha Neurofeedback on Working Memory Capacity in Healthy Participants
Authors: Nawaz Rab , Wood Guilherme , Nisar Humaira , Yap Vooi Voon
Published: February 2023

Neurofeedback, an operant conditioning neuromodulation technique, uses information from brain activities in real-time via brain–computer interface (BCI) technology. This technique has been utilized to enhance the cognitive abilities, including working memory performance, of human beings. The aims of this study are to investigate how alpha neurofeedback can improve working memory performance in healthy participants and to explore the underlying neural mechanisms in a working memory task before and after neurofeedback. Thirty-six participants divided into the NFT group and the control group participated in this study. This study was not blinded, and both the participants and the researcher were aware of their group assignments. Increasing power in the alpha EEG band was used as a neurofeedback in the eyes-open condition only in the NFT group. The data were collected before and after neurofeedback while they were performing the N-back memory task (N = 1 and N = 2). Both groups showed improvement in their working memory performance. There was an enhancement in the power of their frontal alpha and beta activities with increased working memory load (i.e., 2-back). The experimental group showed improvements in their functional connections between different brain regions at the theta level. This effect was absent in the control group. Furthermore, brain hemispheric lateralization was found during the N-back task, and there were more intra-hemisphere connections than inter-hemisphere connections of the brain. These results suggest that healthy participants can benefit from neurofeedback and from having their brain networks changed after the training.
Advances in Animal Models for Studying Bone Fracture Healing
Authors: Gao Hui , Huang Jinming , Wei Quan , He Chengqi
Published: February 2023

Fracture is a common traumatic injury that is mostly caused by traffic accidents, falls, and falls from height. Fracture healing is a long-term and complex process, and the mode of repair and rate of healing are influenced by a variety of factors. The prevention, treatment, and rehabilitation of fractures are issues that urgently need to be addressed. The preparation of the right animal model can accurately simulate the occurrence of fractures, identify and observe normal and abnormal healing processes, study disease mechanisms, and optimize and develop specific treatment methods. We summarize the current status of fracture healing research, the characteristics of different animal models and the modeling methods for different fracture types, analyze their advantages and disadvantages, and provide a reference basis for basic experimental fracture modeling.
Dietary Supplementation with Probiotic Bacillus licheniformis S6 Improves Intestinal Integrity via Modulating Intestinal Barrier Function and Microbial Diversity in Weaned Piglets
Authors: Sun Wenjuan , Chen Wenning , Meng Kun , Cai Long , Li Guiguan , Li Xilong , Jiang Xianren
Published: February 2023

Bacillus licheniformis (B. Licheniformis) has been considered to be an effective probiotic to maintain gut health and boost productivity in the pig industry, but there is no complete understanding of its mechanisms. We determined whether weaned piglets exposed to BL−S6 (probiotic) had altered intestinal barrier function or microbiota composition. In our study, 108 weaned piglets (54 barrows and 54 gilts) were divided equally into three groups, each with six pens and six piglets/pen, and fed a basal diet supplemented without or with antibiotic (40 g/t of Virginiamycin and 500 g/t of Chlortetracycline) or probiotic (1000 g/t of B. Licheniformis) for a 14-day trial. On day 14, one piglet was chosen from each pen to collect blood and intestinal samples. Compared with the control group, dietary supplementation with a probiotic promoted body weight (BW) gain and average daily gains (ADG) while reducing diarrhea incidence (p < 0.05). Probiotics enhanced superoxidase dismutase (SOD) activity and decreased malondialdehyde (MDA) levels in serum (p < 0.05), and increased the level of mRNA expression of SOD1, Nrf2, and HO-1 (p < 0.05) in the jejunum mucosa. Moreover, supplementation with probiotics improved intestinal mucosal integrity as evidenced by higher villus heights and a higher ratio of villus heights to crypt depths (duodenum and jejunum) and higher mRNA and protein levels of occludin and ZO-1 in jejunum mucosa (p < 0.05). The intestinal sIgA levels (p < 0.05) were elevated in the probiotic group, and that of serum immunoglobulin A (IgA) tended to be higher (p = 0.09). Furthermore, weaning piglets who were given probiotics had a better balance of the cecum microbiota, with lactobacillus abundance increased and clostridium_sensu_stricto_1 abundance decreased. In conclusion, dietary supplementation with the probiotic BL−S6 promoted intestinal integrity, which was associated, in part, with modulating intestinal barrier function and microbial diversity in weaned piglets; it may offer a promising alternative to antibiotics to prevent diarrhea.
Overexpression of E-Cadherin Is a Favorable Prognostic Biomarker in Oral Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis
Authors: Lorenzo-Pouso Alejandro I. , Silva Fábio França-Vieira e , Pérez-Jardón Alba , Chamorro-Petronacci Cintia M. , Oliveira-Alves Mônica G. , Álvarez-Calderón-Iglesias Óscar , Caponio Vito Carlo Alberto , Pinti Morena , Perrotti Vittoria , Pérez-Sayáns Mario
Published: February 2023

Oral squamous cell carcinoma (OSCC) is characterized by poor survival, mostly due to local invasion, loco-regional recurrence, and metastasis. Given that the weakening of cell-to-cell adhesion is a feature associated with the migration and invasion of cancer cells, different studies have explored the prognostic utility of cell adhesion molecules such as E-cadherin (E-cad). This study aims to summarize current evidence in a meta-analysis, focusing on the prognostic role of E-cad in OSCC. To find studies meeting inclusion criteria, Scopus, Web of Science, EMBASE, Medline, and OpenGrey databases were systematically assessed and screened. The selection process led to 25 studies, which were considered eligible for inclusion in the meta-analysis, representing a sample of 2553 patients. E-cad overexpression was strongly associated with longer overall survival (OS) with Hazard Ratio (HR)  = 0.41 95% confidence interval (95% CI) (0.32–0.54); p < 0.001 and disease-free survival with HR 0.47 95% CI (0.37–0.61); p < 0.001. In terms of OS, patients with tongue cancer experienced better survivability when expressing E-cad with HR 0.28 95% CI (0.19–0.43); p < 0.001. Globally, our findings indicate the prognostic role of the immunohistochemical assessment of E-cad in OSCC and its expression might acquire a different role based on the oral cavity subsites.
The Conserved Transcriptional Activation Activity Identified in Dual-Specificity Tyrosine-(Y)-Phosphorylation-Regulated Kinase 1
Authors: Ouyang Xiuke , Wang Zhuqing , Wu Bingtong , Yang Xiuxia , Dong Bo
Published: February 2023

Dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1 (DYRK1) encodes a conserved protein kinase that is indispensable to neuron development. However, whether DYRK1 possesses additional functions apart from kinase function remains poorly understood. In this study, we firstly demonstrated that the C-terminal of ascidian Ciona robusta DYRK1 (CrDYRK1) showed transcriptional activation activity independent of its kinase function. The transcriptional activation activity of CrDYRK1 could be autoinhibited by a repression domain in the N-terminal. More excitingly, both activation and repression domains were retained in HsDYRK1A in humans. The genes, activated by the activation domain of HsDYRK1A, are mainly involved in ion transport and neuroactive ligand–receptor interaction. We further found that numerous mutation sites relevant to the DYRK1A-related intellectual disability syndrome locate in the C-terminal of HsDYRK1A. Then, we identified several specific DNA motifs in the transcriptional regulation region of those activated genes. Taken together, we identified a conserved transcription activation domain in DYRK1 in urochordates and vertebrates. The activation is independent of the kinase activity of DYRK1 and can be repressed by its own N-terminal. Transcriptome and mutation data indicate that the transcriptional activation ability of HsDYRK1A is potentially involved in synaptic transmission and neuronal function related to the intellectual disability syndrome.
Bioinformatic Analyses of Peripheral Blood Transcriptome Identify Altered Neutrophil-Related Pathway and Different Transcriptomic Profiles for Acute Pancreatitis in Patients with and without Chylomicronemia Syndrome
Authors: Liu Chia-Lun , Dai Yang-Hong
Published: February 2023

Acute pancreatitis (AP) is a serious inflammatory condition of the pancreas that can be associated with chylomicronemia syndrome (CS). Currently, no study has explored the differences between non-CS-associated AP and CS-associated AP in terms of gene expression. Transcriptomic profiles of blood samples from patients with AP were retrieved from GSE194331 (non-CS-associated) and GSE149607 (CS-associated). GSE31568 was used to examine the linkage between non-CS-associated AP and the expression of micro RNAs (miRNAs). Differentially expressed genes (DEGs) were identified, a gene regulatory network was constructed, and hub genes were defined. Subsequently, single-sample gene set enrichment analysis (ssGSEA) scores of hub genes were calculated to represent their regulatory-level activity. A total of 1851 shared DEGs were identified between non-CS-associated and CS-associated AP. Neutrophils were significantly enriched in both conditions. In non-CS-associated AP, miRNAs including hsa-miR-21, hsa-miR-146a, and hsa-miR-106a demonstrated a lower expression level as compared with the healthy control. Furthermore, the expression patterns and regulatory activities were largely opposite between non-CS-associated and CS-associated AP, with significantly lower estimated neutrophils in the latter case. In summary, we found that the regulation of neutrophils was altered in AP. There was a different gene expression pattern and lower estimated neutrophil infiltration in CS-associated AP. Whether these findings are clinically significant requires further investigation.
Copper Binding and Redox Activity of α-Synuclein in Membrane-Like Environment
Authors: Bacchella Chiara , Camponeschi Francesca , Kolkowska Paulina , Kola Arian , Tessari Isabella , Baratto Maria Camilla , Bisaglia Marco , Monzani Enrico , Bubacco Luigi , Mangani Stefano , Casella Luigi , Dell’Acqua Simone , Valensin Daniela
Published: February 2023

α-Synuclein (αSyn) constitutes the main protein component of Lewy bodies, which are the pathologic hallmark in Parkinson’s disease. αSyn is unstructured in solution but the interaction of αSyn with lipid membrane modulates its conformation by inducing an α-helical structure of the N-terminal region. In addition, the interaction with metal ions can trigger αSyn conformation upon binding and/or through the metal-promoted generation of reactive oxygen species which lead to a cascade of structural alterations. For these reasons, the ternary interaction between αSyn, copper, and membranes needs to be elucidated in detail. Here, we investigated the structural properties of copper-αSyn binding through NMR, EPR, and XAS analyses, with particular emphasis on copper(I) coordination since the reduced state is particularly relevant for oxygen activation chemistry. The analysis was performed in different membrane model systems, such as micellar sodium dodecyl sulfate (SDS) and unilamellar vesicles, comparing the binding of full-length αSyn and N-terminal peptide fragments. The presence of membrane-like environments induced the formation of a copper:αSyn = 1:2 complex where Cu+ was bound to the Met1 and Met5 residues of two helical peptide chains. In this coordination, Cu+ is stabilized and is unreactive in the presence of O2 in catechol substrate oxidation.
MEG Node Degree for Focus Localization: Comparison with Invasive EEG
Authors: Rampp Stefan , Kaltenhäuser Martin , Müller-Voggel Nadia , Doerfler Arnd , Kasper Burkhard S. , Hamer Hajo M. , Brandner Sebastian , Buchfelder Michael
Published: February 2023

Epilepsy surgery is a viable therapy option for patients with pharmacoresistant focal epilepsies. A prerequisite for postoperative seizure freedom is the localization of the epileptogenic zone, e.g., using electro- and magnetoencephalography (EEG/MEG). Evidence shows that resting state MEG contains subtle alterations, which may add information to the workup of epilepsy surgery. Here, we investigate node degree (ND), a graph-theoretical parameter of functional connectivity, in relation to the seizure onset zone (SOZ) determined by invasive EEG (iEEG) in a consecutive series of 50 adult patients. Resting state data were subjected to whole brain, all-to-all connectivity analysis using the imaginary part of coherence. Graphs were described using parcellated ND. SOZ localization was investigated on a lobar and sublobar level. On a lobar level, all frequency bands except alpha showed significantly higher maximal ND (mND) values inside the SOZ compared to outside (ratios 1.11–1.20, alpha 1.02). Area-under-the-curve (AUC) was 0.67–0.78 for all expected alpha (0.44, ns). On a sublobar level, mND inside the SOZ was higher for all frequency bands (1.13–1.38, AUC 0.58–0.78) except gamma (1.02). MEG ND is significantly related to SOZ in delta, theta and beta bands. ND may provide new localization tools for presurgical evaluation of epilepsy surgery.
The Bidirectional Relationship of NPY and Mitochondria in Energy Balance Regulation
Authors: Sousa Diana , Lopes Eduardo , Rosendo-Silva Daniela , Matafome Paulo
Published: February 2023

Energy balance is regulated by several hormones and peptides, and neuropeptide Y is one of the most crucial in feeding and energy expenditure control. NPY is regulated by a series of peripheral nervous and humoral signals that are responsive to nutrient sensing, but its role in the energy balance is also intricately related to the energetic status, namely mitochondrial function. During fasting, mitochondrial dynamics and activity are activated in orexigenic neurons, increasing the levels of neuropeptide Y. By acting on the sympathetic nervous system, neuropeptide Y modulates thermogenesis and lipolysis, while in the peripheral sites, it triggers adipogenesis and lipogenesis instead. Moreover, both central and peripheral neuropeptide Y reduces mitochondrial activity by decreasing oxidative phosphorylation proteins and other mediators important to the uptake of fatty acids into the mitochondrial matrix, inhibiting lipid oxidation and energy expenditure. Dysregulation of the neuropeptide Y system, as occurs in metabolic diseases like obesity, may lead to mitochondrial dysfunction and, consequently, to oxidative stress and to the white adipose tissue inflammatory environment, contributing to the development of a metabolically unhealthy profile. This review focuses on the interconnection between mitochondrial function and dynamics with central and peripheral neuropeptide Y actions and discusses possible therapeutical modulations of the neuropeptide Y system as an anti-obesity tool.
Breathwork Interventions for Adults with Clinically Diagnosed Anxiety Disorders: A Scoping Review
Authors: Banushi Blerida , Brendle Madeline , Ragnhildstveit Anya , Murphy Tara , Moore Claire , Egberts Johannes , Robison Reid
Published: February 2023

Anxiety disorders are the most common group of mental disorders, but they are often underrecognized and undertreated in primary care. Dysfunctional breathing is a hallmark of anxiety disorders; however, mainstays of treatments do not tackle breathing in patients suffering anxiety. This scoping review aims to identify the nature and extent of the available research literature on the efficacy of breathwork interventions for adults with clinically diagnosed anxiety disorders using the DSM-5 classification system. Using the PRISMA extension for scoping reviews, a search of PubMed, Embase, and Scopus was conducted using terms related to anxiety disorders and breathwork interventions. Only clinical studies using breathwork (without the combination of other interventions) and performed on adult patients diagnosed with an anxiety disorder using the DSM-5 classification system were included. From 1081 articles identified across three databases, sixteen were included for the review. A range of breathwork interventions yielded significant improvements in anxiety symptoms in patients clinically diagnosed with anxiety disorders. The results around the role of hyperventilation in treatment of anxiety were contradictory in few of the examined studies. This evidence-based review supports the clinical utility of breathwork interventions and discusses effective treatment options and protocols that are feasible and accessible to patients suffering anxiety. Current gaps in knowledge for future research directions have also been identified.
A Pooled Analysis of Preoperative Inflammatory Biomarkers to Predict 90-Day Outcomes in Patients with an Aneurysmal Subarachnoid Hemorrhage: A Single-Center Retrospective Study
Authors: Nie Zhaobo , Lin Fa , Li Runting , Chen Xiaolin , Zhao Yuanli
Published: February 2023

An inflammatory response after an aneurysmal subarachnoid hemorrhage (aSAH) has always been in the spotlight. However, few studies have compared the prognostic impact of inflammatory biomarkers. Moreover, why these inflammatory biomarkers contribute to a poor prognosis is also unclear. We retrospectively reviewed aSAH patients admitted to our institution between January 2015 and December 2020. The 90-day unfavorable functional outcome was defined as a modified Rankin scale (mRS) of ≥ 3. Independent inflammatory biomarker-related risk factors associated with 90-day unfavorable outcomes were derived from a forward stepwise multivariate analysis. Receiver operating characteristic curve analysis was conducted to identify the best cut-off value of inflammatory biomarkers. Then, patients were divided into two groups according to each biomarker’s cut-off value. To eliminate the imbalances in baseline characteristics, propensity score matching (PSM) was carried out to assess the impact of each biomarker on in-hospital complications. A total of 543 patients were enrolled in this study and 96 (17.7%) patients had unfavorable 90-day outcomes. A multivariate analysis showed that the white blood cell (WBC) count, the systemic inflammation response index, the neutrophil count, the neutrophil-to-albumin ratio, the monocyte count, and the monocyte-to-lymphocyte ratio were independently associated with 90-day unfavorable outcomes. The WBC count showed the best predictive ability (area under the curve (AUC) = 0.710, 95% CI = 0.652–0.769, p < 0.001). After PSM, almost all abnormal levels of inflammatory biomarkers were associated with a higher incidence of pneumonia during hospitalization. The WBC count had the strongest association with poor outcomes. Similar to nearly all other inflammatory biomarkers, the cause of poor prognosis may be the higher incidence of in-hospital pneumonia.
Procrastination in University Students: A Proposal of a Theoretical Model
Authors: Araya-Castillo Luis , Burgos Mildred , González Patricia , Rivera Yuracid , Barrientos Nicolás , Yáñez Jara Víctor , Ganga-Contreras Francisco , Sáez Walter
Published: February 2023

Procrastination is a phenomenon that affects university students and consists of not finishing a task or finishing it late, which has a direct impact on their academic performance. This is relevant because, in a context of high competition, higher education institutions and their decision-makers need to be aware of the factors that influence university students’ procrastination in order to implement actions that favor student attraction and retention. Based on the above, this research aims to propose a theoretical model of procrastination in university students, based on the literature review and content validation assessment through a semi-structured questionnaire. The proposed model is made up of nine dimensions: Psychological, Physiological, Social, Academic, Leisure, Time Management, Resources, Labor, and Environmental. Dimensions were obtained based on adequate levels of content validity provided by the literature and the questionnaire. In the future, the research proposes to study the way in which these dimensions are present in procrastination and design a scale that allows for their measurement.
From Heritage to Sustainability: The Future of the Past in the Hot Arid Climate of the UAE
Authors: Salameh Muna , Touqan Basim
Published: February 2023

Achieving future energy objectives and promoting social, economic, and environmental sustainability can be inspired by heritage and historic structures, which make up a sizeable component of the existing building industry. Heritage architecture and urban sites are known for their capability of positive interaction with the climate to provide better thermal conditions, beside their capability of strengthening cultural identity and improving the economic sector for the related sites. Thus, the main purpose of this research is to highlight the positive sustainable effects (social, economic and environmental) for a proposal of conserving and reconstructing a vernacular heritage architecture site in the hot arid climate in the UAE. The research used a qualitative methodology based on multicriteria descriptive schemes beside ENVI-met software. The research’s findings presented the capability of the conserved heritage area to strengthen the social and cultural identity and improve the economic sector. Moreover, the results demonstrated that the conserved heritage district had a better microclimate and predicted mean vote for outdoor thermal comfort compared to the basic case heritage district prior to rehabilitation and another modern district. The conclusion promotes heritage conservation in hot arid climates and encourages the preservation of vernacular architecture and traditional sites to achieve the sustainable goals for creating sustainable cities that can mitigate climate change.
Restoration of Tilted Buildings via Micropile Underpinning: A Case Study of a Multistory Building Supported by a Raft Foundation
Authors: Elsawwaf Ahmed , El Sawwaf Mostafa , Farouk Ahmed , Aamer Farag , El Naggar Hany
Published: February 2023

This paper presents a real case study of a micropiling process that was developed to stop the continuous tilting of a 9-story residential building in Dakahlia, Egypt. Shortly after the construction of the building, the surface raft foundation exhibited severe settlement problems. In order to carry out a geotechnical investigation, boreholes were drilled around the constructed building. It was discovered that in addition to a thick, soft clay layer in the soil profile, there was also a crucial eccentricity between the centroid of the total building loads and the centroid of the raft. The issue needed to be addressed immediately, and a micropiling system was proposed to satisfy the geotechnical and structural conditions associated with the case history. In addition to describing the field measurements, detailed methodology, and micropile installation process, this paper also presents three different design approaches for determining the number and location of the micropiles. Although the underpinning process itself initially induced some settlement, micropiling the raft proved to be an efficient solution to stop the continuous tilting of the building. A micropile load test confirmed the advantageous effect of the grouting technique used for Type B micropiles, where the grout is injected under high pressure.
Cyclic Behavior of Rectangular Bridge Piers Subjected to the Coupling Effects of Chloride Corrosion and Bidirectional Loading
Authors: Yuan Wenting , Li Xinping , Pang Xiaohang , Tian Chao , Li Zelong , Zhou Peng , Wang Yuren
Published: February 2023

The degradation of seismic performance for RC bridge piers induced by chloride corrosion has previously been studied by treating the earthquake as a unilateral cyclic loading. Such studies do not consider the true response of the pier under the joint effect of corrosion damage and real multi-dimensional earthquake action. Thus, in the present study, the cyclic behavior of rectangular bridge piers subjected to the coupling effects of chloride corrosion and bidirectional loading was numerically investigated. First, the corrosion-induced deterioration of material mechanical properties is introduced. Second, the numerical model of two corroded piers is built and validated with the test results in the literature. Then, the time-dependent biaxial seismic performance of a rectangular bridge pier under the circular-shaped (CS) biaxial displacement pattern, square-shaped (SS) biaxial displacement pattern, uniaxial displacement in the X-direction (UX) pattern, and uniaxial displacement in the Y-direction (UY) pattern is analyzed using the validated model. The simulation results conclude that the trajectory of biaxial loading paths and corrosion levels significantly influence the peak force, deformation capacity, and dissipated energy of the piers. The biaxial loading path effect for the corrosive pier includes two stages with different biaxial force trajectory characteristics. Compared with the uncorroded pier, the corrosion level of 13.7% and biaxial loading induces up to a 40% reduction in strength and a 54% decrease in the residual ultimate displacement of the corroded pier. For the same corrosion degree, the dissipated energy under the SS biaxial displacement path is the largest among the four loading paths.
Virtual Reality-Assisted Awake Craniotomy: A Retrospective Study
Authors: Bernard Florian , Clavreul Anne , Casanova Morgane , Besnard Jérémy , Lemée Jean-Michel , Soulard Gwénaëlle , Séguier Renaud , Menei Philippe
Published: February 2023

Background: Awake craniotomy (AC) with brain mapping for language and motor functions is often performed for tumors within or adjacent to eloquent brain regions. However, other important functions, such as vision and visuospatial and social cognition, are less frequently mapped, at least partly due to the difficulty of defining tasks suitable for the constrained AC environment. Objective: The aim of this retrospective study was to demonstrate, through illustrative cases, how a virtual reality headset (VRH) equipped with eye tracking can open up new possibilities for the mapping of language, the visual field and complex cognitive functions in the operating room. Methods: Virtual reality (VR) tasks performed during 69 ACs were evaluated retrospectively. Three types of VR tasks were used: VR-DO80 for language evaluation, VR-Esterman for visual field assessment and VR-TANGO for the evaluation of visuospatial and social functions. Results: Surgery was performed on the right hemisphere for 29 of the 69 ACs performed (42.0%). One AC (1.5%) was performed with all three VR tasks, 14 ACs (20.3%) were performed with two VR tasks and 54 ACs (78.3%) were performed with one VR task. The median duration of VRH use per patient was 15.5 min. None of the patients had “VR sickness”. Only transitory focal seizures of no consequence and unrelated to VRH use were observed during AC. Patients were able to perform all VR tasks. Eye tracking was functional, enabling the medical team to analyze the patients’ attention and exploration of the visual field of the VRH directly. Conclusions: This preliminary experiment shows that VR approaches can provide neurosurgeons with a way of investigating various functions, including social cognition during AC. Given the rapid advances in VR technology and the unbelievable sense of immersion provided by the most recent devices, there is a need for ongoing reflection and discussions of the ethical and methodological considerations associated with the use of these advanced technologies in AC and brain mapping procedures.
Perturbation of Autophagy by a Beclin 1-Targeting Stapled Peptide Induces Mitochondria Stress and Inhibits Proliferation of Pancreatic Cancer Cells
Authors: Li Na , Zhang Xiaozhe , Chen Jingyi , Gao Shan , Wang Lei , Zhao Yanxiang
Published: February 2023

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer, with a dismal five-year survival rate of less than 10%. PDAC possesses prominent genetic alterations in the oncogene KRAS and tumor suppressors p53, SMAD4 and CDKN2A. However, efforts to develop targeted drugs against these molecules have not been successful, and novel therapeutic modalities for PDAC treatment are urgently needed. Autophagy is an evolutionarily conserved self-degradative process that turns over intracellular components in a lysosome-dependent manner. The role of autophagy in PDAC is complicated and context-dependent. Elevated basal autophagy activity has been detected in multiple human PDAC cell lines and primary tumors resected from patients. However, clinical trials using chloroquine (CQ) to inhibit autophagy failed to show therapeutic efficacy. Here we show that a Beclin 1-targeting stapled peptide (Tat-SP4) developed in our lab further enhanced autophagy in multiple PDAC cell lines possessing high basal autophagy activity. Tat-SP4 also triggered faster endolysosomal degradation of EGFR and induced significant mitochondria stress as evidenced by partial loss of Δψ, increased level of ROS and reduced OXPHOS activity. Tat-SP4 exerted a potent anti-proliferative effect in PDAC cell lines in vitro and prohibited xenograft tumor growth in vivo. Intriguingly, excessive autophagy has been reported to trigger a unique form of cell death termed autosis. Tat-SP4 does induce autosis-like features in PDAC cells, including mitochondria stress and non-apoptotic cell death. Overall, our study suggests that autophagy perturbation by a Beclin 1-targeting peptide and the resulting autosis may offer a new strategy for PDAC drug discovery.
F-Box Protein 43, Stabilized by N6-Methyladenosine Methylation, Enhances Hepatocellular Carcinoma Cell Growth and Invasion via Promoting p53 Degradation in a Ubiquitin Conjugating Enzyme E2 C-Dependent Manner
Authors: Zhou Huijun , Zeng Chong , Liu Jie , Luo Haijun , Huang Wei
Published: February 2023

The roles of F-box protein 43 (FBXO43) in carcinogenesis have been rarely revealed. The present study investigates the expression, function, and underlying mechanism of FBXO43 in hepatocellular carcinoma (HCC). Firstly, the expression and clinical significance of FBXO43 in HCC were investigated bioinformatically and experimentally using online omics data and local tissue samples. The role of N6-methyladenosine modification (m6A) of mRNA in regulating FBXO43 expression and the effects of m6A/FBXO43 axis alteration on cell proliferation and invasion were investigated further. Moreover, the underlying mechanism of the oncogenic FBXO43 was also explored. The results demonstrated that FBXO43 was significantly upregulated in HCC and was positively correlated with advanced progression and poor prognosis in patients. METTL3 and IGF2BP2 expressions were positively correlated with FBXO43 expression and served as the writer and reader of FBXO43 m6A, respectively, which stabilized and upregulated FBXO43 mRNA in HCC. FBXO43 silencing significantly reduced cell proliferation and invasion, and ectopic expression of FBXO43 could significantly restore the inhibitory effects caused by METTL3 and IGF2BP2 depletion in HCC cells. Mechanistically, FBXO43 depletion reduced the expression of UBE2C, a p53 ubiquitin-conjugating enzyme, suppressed proteasomal degradation of p53, and thus inhibited cell proliferation and invasion in HCC. In summary, the present study revealed that METTL3/IGF2BP2 mediated m6A contributed to the upregulation of FBXO43 that promoted the malignant progression of HCC by stimulating p53 degradation in a UBE2C-dependent manner, highlighting the promising application of FBXO43 as a target in HCC treatment.
Inhibition of Macropinocytosis Enhances the Sensitivity of Osteosarcoma Cells to Benzethonium Chloride
Authors: Xia Haichao , Huang Yanran , Zhang Lulu , Luo Lijuan , Wang Xiaoxuan , Lu Qiuping , Xu Jingtao , Yang Chunmei , Jiwa Habu , Liang Shiqiong , Xie Liping , Luo Xiaoji , Luo Jinyong
Published: February 2023

Osteosarcoma (OS) is a primary malignant tumor of bone. Chemotherapy is one of the crucial approaches to prevent its metastasis and improve prognosis. Despite continuous improvements in the clinical treatment of OS, tumor resistance and metastasis remain dominant clinical challenges. Macropinocytosis, a form of non-selective nutrient endocytosis, has received increasing attention as a novel target for cancer therapy, yet its role in OS cells remains obscure. Benzethonium chloride (BZN) is an FDA-approved antiseptic and bactericide with broad-spectrum anticancer effects. Here, we described that BZN suppressed the proliferation, migration, and invasion of OS cells in vitro and in vivo, but simultaneously promoted the massive accumulation of cytoplasmic vacuoles as well. Mechanistically, BZN repressed the ERK1/2 signaling pathway, and the ERK1/2 activator partially neutralized the inhibitory effect of BZN on OS cells. Subsequently, we demonstrated that vacuoles originated from macropinocytosis and indicated that OS cells might employ macropinocytosis as a compensatory survival mechanism in response to BZN. Remarkably, macropinocytosis inhibitors enhanced the anti-OS effect of BZN in vitro and in vivo. In conclusion, our results suggest that BZN may inhibit OS cells by repressing the ERK1/2 signaling pathway and propose a potential strategy to enhance the BZN-induced inhibitory effect by suppressing macropinocytosis.
Lenalidomide in Multiple Myeloma: Review of Resistance Mechanisms, Current Treatment Strategies and Future Perspectives
Authors: Kulig Piotr , Milczarek Sławomir , Bakinowska Estera , Szalewska Laura , Baumert Bartłomiej , Machaliński Bogusław
Published: February 2023

Multiple myeloma (MM) is the second most common hematologic malignancy, accounting for approximately 1% of all cancers. Despite the initial poor prognosis for MM patients, their life expectancy has improved significantly with the development of novel agents. Immunomodulatory drugs (IMiDs) are widely used in MM therapy. Their implementation has been a milestone in improving the clinical outcomes of patients. The first molecule belonging to the IMiDs was thalidomide. Subsequently, its novel derivatives, lenalidomide (LEN) and pomalidomide (POM), were implemented. Almost all MM patients are exposed to LEN, which is the most commonly used IMiD. Despite the potent anti-MM activity of LEN, some patients eventually relapse and become LEN-resistant. Drug resistance is one of the greatest challenges of modern oncology and has become the main cause of cancer treatment failures. The number of patients receiving LEN is increasing, hence the problem of LEN resistance has become a great obstacle for hematologists worldwide. In this review, we intended to shed more light on the pathophysiology of LEN resistance in MM, with particular emphasis on the molecular background. Moreover, we have briefly summarized strategies to overcome LEN resistance and we have outlined future directions.
MR Intensity Normalization Methods Impact Sequence Specific Radiomics Prognostic Model Performance in Primary and Recurrent High-Grade Glioma
Authors: Salome Patrick , Sforazzini Francesco , Brugnara Gianluca , Kudak Andreas , Dostal Matthias , Herold-Mende Christel , Heiland Sabine , Debus Jürgen , Abdollahi Amir , Knoll Maximilian
Published: February 2023

Purpose: This study investigates the impact of different intensity normalization (IN) methods on the overall survival (OS) radiomics models’ performance of MR sequences in primary (pHGG) and recurrent high-grade glioma (rHGG). Methods: MR scans acquired before radiotherapy were retrieved from two independent cohorts (rHGG C1: 197, pHGG C2: 141) from multiple scanners (15, 14). The sequences are T1 weighted (w), contrast-enhanced T1w (T1wce), T2w, and T2w-FLAIR. Sequence-specific significant features (SF) associated with OS, extracted from the tumour volume, were derived after applying 15 different IN methods. Survival analyses were conducted using Cox proportional hazard (CPH) and Poisson regression (POI) models. A ranking score was assigned based on the 10-fold cross-validated (CV) concordance index (C-I), mean square error (MSE), and the Akaike information criterion (AICs), to evaluate the methods’ performance. Results: Scatter plots of the 10-CV C-I and MSE against the AIC showed an impact on the survival predictions between the IN methods and MR sequences (C1/C2 C-I range: 0.62–0.71/0.61–0.72, MSE range: 0.20–0.42/0.13–0.22). White stripe showed stable results for T1wce (C1/C2 C-I: 0.71/0.65, MSE: 0.21/0.14). Combat (0.68/0.62, 0.22/0.15) and histogram matching (HM, 0.67/0.64, 0.22/0.15) showed consistent prediction results for T2w models. They were also the top-performing methods for T1w in C2 (Combat: 0.67, 0.13; HM: 0.67, 0.13); however, only HM achieved high predictions in C1 (0.66, 0.22). After eliminating IN impacted SF using Spearman’s rank-order correlation coefficient, a mean decrease in the C-I and MSE of 0.05 and 0.03 was observed in all four sequences. Conclusion: The IN method impacted the predictive power of survival models; thus, performance is sequence-dependent.
Development and Internal Validation of a Risk Prediction Model to Identify Myeloma Based on Routine Blood Tests: A Case-Control Study
Authors: Smith Lesley , Carmichael Jonathan , Cook Gordon , Shinkins Bethany , Neal Richard D.
Published: February 2023

Myeloma is one of the hardest cancers to diagnose in primary care due to its rarity and non-specific symptoms. A rate-limiting step in diagnosing myeloma is the clinician considering myeloma and initiating appropriate investigations. We developed and internally validated a risk prediction model to identify those with a high risk of having undiagnosed myeloma based on results from routine blood tests taken for other reasons. A case-control study, based on 367 myeloma cases and 1488 age- and sex-matched controls, was used to develop a risk prediction model including results from 15 blood tests. The model had excellent discrimination (C-statistic 0.85 (95%CI 0.83, 0.89)) and good calibration (calibration slope 0.87 (95%CI 0.75, 0.90)). At a prevalence of 15 per 100,000 population and a probability threshold of 0.4, approximately 600 patients would need additional reflex testing to detect one case. We showed that it is possible to combine signals and abnormalities from several routine blood test parameters to identify individuals at high-risk of having undiagnosed myeloma who may benefit from additional reflex testing. Further work is needed to explore the full potential of such a strategy, including whether it is clinically useful and cost-effective and how to make it ethically acceptable.