bluuebunny/crossref_metadata_2025 huggingface dataset:
A Numerical Implementation of Fractional-Order PID Controllers for Autonomous Vehicles
Authors: Batiha Iqbal M. , Ababneh Osama Y. , Al-Nana Abeer A. , Alshanti Waseem G. , Alshorm Shameseddin , Momani Shaher
Published: March 2023

In the context of reaching the best way to control the movement of autonomous cars linearly and angularly, making them more stable and balanced on different roads and ensuring that they avoid road obstacles, this manuscript chiefly aims to reach the optimal approach for a fractional-order PID controller (or PIγDρ-controller) instead of the already classical one used to provide smooth automatic parking for electrical autonomous cars. The fractional-order PIγDρ-controller is based on the particle swarm optimization (PSO) algorithm for its design, with two different approximations: Oustaloup’s approximation and the continued fractional expansion (CFE) approximation. Our approaches to the fractional-order PID using the results of the PSO algorithm are compared with the classical PID that was designed using the results of the Cohen–Coon, Ziegler–Nichols and bacteria foraging algorithms. The scheme represented by the proposed PIγDρ-controller can provide the system of the autonomous vehicle with more stable results than that of the PID controller.
Ischemic Conditioning to Reduce Fatigue in Isometric Skeletal Muscle Contraction
Authors: Allois Ruben , Pagliaro Pasquale , Roatta Silvestro
Published: March 2023

Ischemic preconditioning (IPC) is a non-invasive protective maneuver that alternates short periods of occlusion and reperfusion of tissue blood flow. Given the heterogeneity in the magnitude and frequency of IPC-induced improvements in physical performance, here we aimed to investigate, in a well-controlled experimental set-up, the local effects of IPC in exposed muscles in terms of tissue oxygenation and muscle fatigue. Nineteen subjects were enrolled in one of the two groups, IPC (3 × 5/5 min right arm ischemia/reperfusion; cuff inflations 250 mmHg) and SHAM (3 × 5/5 min pseudo ischemia/reperfusion; 20 mmHg). The subjects performed a fatiguing contraction protocol before and 30 min after the IPC treatment, consisting of unilateral intermittent isometric elbow flexions (3 s ON/OFF, 80% of maximal voluntary contraction) until exhaustion. While muscle strength did not differ between groups, post- vs. pre-treatment endurance was significantly reduced in the SHAM group (4.1 ± 1.9 vs. 6.4 ± 3.1 repetitions until exhaustion, p < 0.05) but maintained in IPC (7.3 ± 2.0 vs. 7.1 ± 4.3, n.s.). The decrease in tissue oxygenation and the increase in deoxygenated hemoglobin were significantly reduced post- vs. pre-IPC (p < 0.05), but not post- vs. pre-SHAM. The results suggest that IPC delays the onset of fatigue likely through improved metabolic efficiency of muscles.
Normal β-Cell Glut2 Expression Is not Required for Regulating Glucose-Stimulated Insulin Secretion and Systemic Glucose Homeostasis in Mice
Authors: Bathina Siresha , Faniyan Tumininu S. , Bainbridge Lauren , Davis Autumn , Chhabra Kavaljit H.
Published: March 2023

Objective: Glucose transporter 2 (GLUT2) is expressed in the pancreatic β-cell, intestine, liver, and kidney in mice. Although GLUT2 is considered as a major regulator of insulin secretion, in vivo contribution of β-cell Glut2 to glucose-stimulated insulin secretion and systemic glucose homeostasis is undefined. Therefore, the main objective of this study is to determine the role of β-cell Glut2 in regulating insulin secretion and blood glucose levels in mice. Methods: We produced mice in which we can knock down Glut2 at a desired time specifically in β-cells (β-Glut2 KD) by crossing Glut2LoxP/LoxP mice with Ins1CreERT2 mouse strain and using the Cre-Lox recombination technique. We measured fasting blood glucose levels, glucose tolerance, and glucose-stimulated insulin secretion in the β-Glut2 KD mice. We used qRT-PCR and immunofluorescence to validate the deficiency of β-cell Glut2 in β-Glut2 KD mice. Results: We report that both male and female β-Glut2 KD mice have normal glucose-stimulated insulin secretion. Moreover, the β-Glut2 KD mice exhibit normal fasting blood glucose levels and glucose tolerance. The β-Glut2 KD mice have upregulated GLUT1 in islets. Conclusions: Our findings demonstrate that normal β-cell Glut2 expression is not essential for regulating glucose-stimulated insulin secretion and systemic glucose homeostasis in mice. Therefore, the currently assumed role of β-cell GLUT2 in regulating insulin secretion and blood glucose levels needs to be recalibrated. This will allow an opportunity to determine the contribution of other β-cell glucose transporters or factors whose normal expression may be necessary for mediating glucose stimulated insulin secretion.
An Efficient Bayesian Method for Estimating the Degree of the Skewness of X Chromosome Inactivation Based on the Mixture of General Pedigrees and Unrelated Females
Authors: Kong Yi-Fan , Li Shi-Zhu , Wang Kai-Wen , Zhu Bin , Yuan Yu-Xin , Li Meng-Kai , Zhou Ji-Yuan
Published: March 2023

Skewed X chromosome inactivation (XCI-S) has been reported to be associated with some X-linked diseases. Several methods have been proposed to estimate the degree of XCI-S (denoted as γ) for quantitative and qualitative traits based on unrelated females. However, there is no method available for estimating γ based on general pedigrees. Therefore, in this paper, we propose a Bayesian method to obtain the point estimate and the credible interval of γ based on the mixture of general pedigrees and unrelated females (called mixed data for brevity), which is also suitable for only general pedigrees. We consider the truncated normal prior and the uniform prior for γ. Further, we apply the eigenvalue decomposition and Cholesky decomposition to our proposed methods to accelerate the computation speed. We conduct extensive simulation studies to compare the performances of our proposed methods and two existing Bayesian methods which are only applicable to unrelated females. The simulation results show that the incorporation of general pedigrees can improve the efficiency of the point estimation and the precision and the accuracy of the interval estimation of γ. Finally, we apply the proposed methods to the Minnesota Center for Twin and Family Research data for their practical use.
Diversity of HLA-A2-Restricted and Immunodominant Epitope Repertoire of Human T-Lymphotropic Virus Type 1 (HTLV-1) Tax Protein: Novel Insights among N-Terminal, Central and C-Terminal Regions
Authors: Pereira-Santos Thaiza Aline , da Rocha Anderson Santos , Lopes-Ribeiro Ágata , Corrêa-Dias Laura Cardoso , Melo-Oliveira Patrícia , Reis Erik Vinicius de Sousa , da Fonseca Flávio Guimarães , Barbosa-Stancioli Edel Figueiredo , Tsuji Moriya , Coelho-dos-Reis Jordana Grazziela Alves
Published: March 2023

The present study sought to search for the immunodominance related to the N-terminal, Central and C-terminal regions of HTLV-1 Tax using novel, cutting-edge peptide microarray analysis. In addition, in silico predictions were performed to verify the presence of nine amino acid peptides present along Tax restricted to the human leukocyte antigen (HLA)-A2.02*01 haplotype, as well as to verify the ability to induce pro-inflammatory and regulatory cytokines, such as IFN-γ and IL-4, respectively. Our results indicated abundant dose-dependent reactivity for HLA-A*02:01 in all regions (N-terminal, Central and C-terminal), but with specific hotspots. Furthermore, the results of fold-change over the Tax11–19 reactivity obtained at lower concentrations of HLA-A*02:01 reveal that peptides from the three regions contain sequences that react 100 times more than Tax11–19. On the other hand, Tax11–19 has similar or superior HLA-A*02:01 reactivity at higher concentrations of this haplotype. The in silico analysis showed a higher frequency of IFN-γ-inducing peptides in the N-terminal portion, while the C-terminal portion showed a higher frequency of IL-4 inducers. Taken together, these results shed light on the search for new Tax immunodominant epitopes, in addition to the canonic Tax11–19, for the rational design of immunomodulatory strategies for HTLV-1 chronic diseases.
Spatiotemporal Regulation of FMNL2 by N-Terminal Myristoylation and C-Terminal Phosphorylation Drives Rapid Filopodia Formation
Authors: Lorenzen Lina , Frank Dennis , Schwan Carsten , Grosse Robert
Published: March 2023

The actin nucleating and polymerizing formin-like 2 (FMNL2) is upregulated in several cancers and has been shown to play important roles in cell migration, invasion, cell–cell adhesion and filopodia formation. Here, using structured illumination microscopy we show that FMNL2 promotes rapid and highly dynamic filopodia formation in epithelial cells while remaining on the tip of the growing filopodia. This filopodia tip localization depends fully on its N-terminal myristoylation. We further show that FMNL2-dependent filopodia formation requires its serine 1072 phosphorylation within the diaphanous-autoregulatory domain (DAD) by protein kinase C (PKC) α. Consistent with this, filopodia formation depends on PKC activity and PKCα localizes to the base of growing filopodia. Thus, a PKCα–FMNL2 signaling module spatiotemporally controls dynamic filopodia formation.
Microfluidic Platform Integrated with Carbon Nanofibers-Decorated Gold Nanoporous Sensing Device for Serum PSA Quantification
Authors: Felici Emiliano , Regiart Matías , Pereira Sirley , Ortega Francisco , Angnes Lúcio , Messina Germán , Fernández-Baldo Martín
Published: March 2023

Prostate cancer is a disease with a high incidence and mortality rate in men worldwide. Serum prostate-specific antigens (PSA) are the main circulating biomarker for this disease in clinical practices. In this work, we present a portable and reusable microfluidic device for PSA quantification. This device comprises a polymethyl methacrylate microfluidic platform coupled with electrochemical detection. The platinum working microelectrode was positioned in the outflow region of the microchannel and was modified with carbon nanofibers (CNF)-decorated gold nanoporous (GNP) structures by the dynamic hydrogen bubble template method, through the simultaneous electrodeposition of metal precursors in the presence of CNF. CNF/GNP structures exhibit attractive properties, such as a large surface to volume ratio, which increases the antibody’s immobilization capacity and the electroactive area. CNFs/GNP structures were characterized by scanning electron microscopy, energy dispersive spectrometry, and cyclic voltammetry. Anti-PSA antibodies and HRP were employed for the immune-electrochemical reaction. The detection limit for the device was 5 pg mL−1, with a linear range from 0.01 to 50 ng mL−1. The coefficients of variation within and between assays were lower than 4.40%, and 6.15%, respectively. Additionally, its clinical performance was tested in serum from 30 prostate cancer patients. This novel device was a sensitive, selective, portable, and reusable tool for the serological diagnosis and monitoring of prostate cancer.
Recent Advances in Recognition Receptors for Electrochemical Biosensing of Mycotoxins—A Review
Authors: Kaur Manpreet , Gaba Jyoti , Singh Komal , Bhatia Yashika , Singh Anoop , Singh Narinder
Published: March 2023

Mycotoxins are naturally occurring toxic secondary metabolites produced by fungi in cereals and foodstuffs during the stages of cultivation and storage. Electrochemical biosensing has emerged as a rapid, efficient, and economical approach for the detection and quantification of mycotoxins in different sample media. An electrochemical biosensor consists of two main units, a recognition receptor and a signal transducer. Natural or artificial antibodies, aptamers, molecularly imprinted polymers (MIP), peptides, and DNAzymes have been extensively employed as selective recognition receptors for the electrochemical biosensing of mycotoxins. This article affords a detailed discussion of the recent advances and future prospects of various types of recognition receptors exploited in the electrochemical biosensing of mycotoxins.
HPTLC-Bioluminescent Bioautography Screening of Herbal Teas for Adulteration with Hypolipidemic Drugs
Authors: Wang Yuting , Xi Xingjun , Wang Liao , Chen Yisheng
Published: March 2023

Teas based on nutraceutical herbs are an effective tool against hyperlipidemia. However, the adulteration with chemical drugs is frequently detected. By coupling bioluminescent bioautography with high performance thin-layer chromatography (HPTLC), we developed a facile method suitable for screening hypolipidemic drugs (ciprofibrate and bezafibrate) adulteration in five different herbal teas (lotus leaf, Apocynum, Ginkgo biloba, Gynostemia and chrysanthemum). First, the sensitivity of a bioluminescent bacteria to the analyte was evaluated on different HPTLC layer materials, revealing that the best performance was achieved on the silica gel layer. On this basis, sample extracts were separated on silica gel plates via a standardized HPTLC procedure, forming a selective detection window for the targeted compound. Then, the separation results were rapidly visualized by the bioluminescence inhibition of bacteria cells within 6 min after dipping. The observed inhibition displayed an acceptable limit of detection (<20 ng/zone or 2 mg/kg) and linearity (R2 ≥ 0.9279) within a wide concentration range (50–1000 ng/zone). Furthermore, the optimized method was performed with artificially adulterated samples and the recovery rates were determined to be within the range of 71% to 91%, bracing its practical reliability. Showing superiorly high simplicity, throughput and specificity, this work demonstrated that the analytical method jointly based on HPTLC and bioautography was an ideal tool for screening bioactive compounds in complex biological matrix.
Perceptions of Knowledge, Disease Impact and Predictive Genetic Testing in Family Members at Risk to Develop Early-Onset Alzheimer’s Disease (EOAD) and Their Levels of Suicidal Ideation: A Mixed Study
Authors: Reyes-Domínguez Yesica Arlae , Figuera Luis E. , Brambila-Tapia Aniel Jessica Leticia
Published: March 2023

Early-onset Alzheimer’s disease (EOAD) is an autosomal dominantly inherited disease, in which a founder effect has been described for A431E mutation in the PSEN1 gene, with most of the affected patients being residents of a small town in the state of Jalisco in Mexico. To date, no studies have been performed in order to know the impact of the disease on this population. Therefore, the objective of this study was to investigate the perceptions in the knowledge, the impact of the disease and the intention to take the predictive genetic testing in the population at genetic risk of Jalisco. For this objective, we performed a mixed study that included a qualitative methodology (semi-structured interviews), and, in addition, we measured suicidal ideation, stress and depression with quantitative instruments in order to compare them with a control group. Of the 28 invited individuals, 9 accepted to participate, from which, 5 (55.56%) participants did not know their genetic risk to develop the disease and 5 (55.56%) would want to take the predictive genetic testing in order to be prepared to face the disease; however, among those who did not want to know, 2 individuals (22.22%) mentioned that they would consider suicide if they were positive for the pathogenic variant. On the impact of the disease, we detected that the adaptation to the familiar’s needs was the most frequent answer, including changes in their lifestyle (being responsible since very young, changes in social life and familiar dynamic), this being their main stressor, followed by changes in plans for the future and contemplating the possibility of being affected. Although no differences in stress and depression between groups were observed, we detected that suicidal ideation was significantly higher in the group of cases. These results highlight the importance to involve all the family in genetic counseling in order to clarify any doubts and also to attend to them psychologically to prevent suicidal ideation and attempts.
Integrated Kinetic Fins for Western Facades in Territories with Low Solar Altitudes
Authors: Fahmy Marwa Kamal , Eltaweel Ahmad , Rizi Rana Abdollahi , Imani Negin
Published: March 2023

Insufficient daylighting can negatively affect working quality and productivity and increase lighting energy consumption in buildings. Particularly, the western orientation has a non-uniform daylighting distribution, especially at the zone next to the window resulting from the unequal radiation distribution of sunlight. Therefore, this study presents an innovative system known as Integrated Kinetic Fins (IKF), which can respond parametrically to the sun’s movement; to enhance the daylighting distribution during the late working hours for the western façades and decrease the high illuminance daylighting spots near the windows. The study optimizes the fin parameters based on a selected territory; then, the fi angles are automatically controlled. The IKF is applicable in regions with clear skies and low solar altitudes. Finally, a comparison between a traditional kinetic system and the IKF is made, and the results are reported. The system shows an enhancement of daylight distribution during these late hours, where the contrast has been improved by 22% and uniformity has been enhanced by 10%, which consequently contributes to reducing potential glare.
Multi-Technique Approach by Traditional and Innovative Methodologies to Support the Restoration of a Wall Painting from the 16th Century at Palazzo Gallo in Bagnaia, Viterbo, Central Italy
Authors: Vettraino Riccardo , Valentini Valeria , Pogliani Paola , Ricci Marco , Laureti Stefano , Calvelli Serena , Zito Rocco , Lanteri Luca , Pelosi Claudia
Published: March 2023

This paper summarizes the main results of the study, diagnostics, and restorations conducted and applied to a 16th century wall painting (a portion of the frieze and the Riario coat of arm) in Palazzo Gallo (Bagnaia, Viterbo district—central Italy) recently concluded, which was also the subject of a master’s degree thesis in Conservation and Restoration of Cultural Heritage at the University of Tuscia, Viterbo. Innovative imaging techniques were used for the first time on a wall painting on-site: hypercolorimetric multispectral imaging (HMI) and pulse-compression thermography (PuCT), combined with more traditional analysis such as X-ray fluorescence spectroscopy, Fourier transform infrared spectroscopy, and cross-section investigation. HMI allowed for mapping the conservation status before and after the removal of the scialbo layer that covered the original paintings. It also allowed different areas of the painting to be compared and for verifying the effectiveness of the cleaning. PuCT enabled the detection of cracks and discontinuities in the ground layers and to evaluate the depth of such anomalies, giving valuable support in the consolidation step. Moreover, passive thermography was used to monitor the penetration level of a hydraulic mortar in real time, a technique that was greatly helpful for verifying the successful fill and consolidation of voids beneath the pictorial layer. Overall, the multi-technique approach reported here was of considerable assistance for restoration of the mentioned artwork, the result of which has also been documented.
Development of Concrete Extrusion Nozzle for Producing Free-Form Concrete Panels and Extrusion Test
Authors: Youn Jongyoung , Jeong Kyeongtae , Kim Jihye , Kim Hyekwon , Lee Donghoon
Published: March 2023

FCP (Free-form Concrete Panel) is used to easily realize the huge and complex curved surfaces of free-form buildings, and research on FCP manufacturing technology is being conducted. However, as the concrete was extruded manually into the manufactured mold, the precision of the FCP was lowered and errors occurred. Therefore, this study developed concrete extrusion equipment that includes a nozzle part, an open/close part, and a control part, according to the required performance derived from previous research analysis. The mixing ratio of concrete was selected at an appropriate value of W/C 38% and extruded uniformly with a width of 60 mm and a thickness of 22 mm. Depending on the opening/closing function, it was possible to open and close at the desired position. The concrete extrusion nozzle for FCP production is the basic equipment, and miniaturization and automation of the nozzle are required in the future. This is expected to contribute to the development of new free-form construction technology and equipment.
Seismic Assessment of the Archangeloi (Başmelekler) Church in Kumyaka, Türkiye
Authors: Gunes Baris
Published: March 2023

This study describes the seismic assessment of the Archangeloi (Başmelekler) Church in Kumyaka (Sige), Türkiye. The Archangeloi Church is an important religious monument that has survived to the present day from the eighth century. Through field surveys, the structural system, damages and masonry texture were determined. Pushover analysis was performed with OpenSees software, which has an advanced nonlinear analysis capability. The Damage TC3D material damage model with advanced features was used, allowing a more stable and effective application of mixed implicit–explicit analyses. Displacement-based pushover analyses were performed with different control points, and the damage patterns, ultimate strength and strength reductions were obtained effectively. The pushover analysis reflected the structure’s expected behavior, especially its post-ultimate strength and failure patterns, owing to the material damage model’s advanced mixed implicit–explicit capacity. Kinematic analyses were performed to determine the overturning mechanisms. Due to the analysis assumptions and pre-assigned failure mechanisms, lower failure multipliers were obtained with the kinematic analysis than with the pushover analysis. Under seismic loading, the structure did not satisfy the required performance targets. Extensive damage occurred throughout the structure, even at the lowest performance levels. The selected modeling/analysis method and material damage model to determine this church’s structural performance reflect the expected structural behavior.
Evaluation and Optimization Paths of Design Elements of Underground Building Atria Based on IPA–Kano Model
Authors: Jia Xinming , Yan Bo , Wang Jinyao , Fang Ling
Published: March 2023

The interior of an underground atrium is often a combination of multiple design elements. The lack of methodology and quantitative data support makes it impossible for developers and operators to know the public’s preferences for further renovation, which seriously hinders the sustainable development of underground atria. This paper addresses this issue by evaluating the IPA–Kano model for underground atria with three cases selected in the main urban area of Chongqing for comparison. Then, three types of design elements have been identified to have different impacts on underground building atria on the basis of analyzing the relationship between design elements and users’ subjective perceptions of underground building atria. They are the basic, importance, and attraction elements. Finally, the optimization path for underground building atria is determined by integrating the actual performance of these three types of design elements. It is indicated that design elements such as seating, interface, and signage must be prioritized for improvement.
Numerical Analysis of Modified PVA Fiber Rubber Concrete in Frame Beams
Authors: Li Lijuan , Xing Fang , Xu Zhijun , Chen Wang , Chen Wuxin , Li Yongquan
Published: March 2023

The feasibility of PVA fiber rubber concrete modified by modifier in the structure was investigated using the portal frame as the research object. The basic mechanical properties of modified PVA rubber concrete materials were tested mechanically first, and then ABAQUS was used to establish the ordinary concrete portal frame model, and after confirming the model’s rationality, the rubber concrete, PVA rubber concrete, and modified PVA rubber concrete models were established on this basis, and the displacement and strain comparison analysis with ordinary concrete was carried out. The simulation results show that using PVA rubber concrete material in the concrete frame structure can improve the large deformation of rubber concrete, and using PVA rubber concrete treated with a modifier can improve structural strength and deformation even more.
Impact of Pandemic Safety Measures on Students’ Thermal Comfort—Case Study: Romania
Authors: Rus Tania , Moldovan Raluca , Albu Horatiu , Beu Dorin
Published: March 2023

The indoor environmental quality of a building has attracted everyone’s attention since a worldwide pandemic was declared and forced people indoors. After several months, people were able to return to their usual activities, but with strict safety measures added due to the circumstances. This paper focuses on the impact of safety measures on students’ thermal comfort, a case study performed in a continental climate zone, during the winter. The methodology used involved the collection of both quantitative and qualitative data. Descriptive statistics and frequencies alongside correlations and cross-tabular methods were used to analyze the collected data. The results indicated that the predicted mean vote (PMV) underestimated students’ thermal perception. A difference of 1.5 °C was found between the operative neutral temperature of the PMV and students’ thermal sensation votes while wearing masks. Likewise, a lower neutral operative temperature was found for students wearing masks than for those without masks. Students wearing masks preferred a slightly cooler environment and a significant difference was found (p = 0.001) between students’ thermal comfort votes. All of these findings indicate that there is a potential for energy savings without affecting students’ thermal comfort.
Do Not Forget about Hormonal Therapy for Recurrent Endometrial Cancer: A Review of Options, Updates, and New Combinations
Authors: Wagner Vincent M. , Backes Floor J.
Published: March 2023

Hormonal therapy has long been a treatment modality for recurrent endometrial cancer. It is appealing for patients with low-grade, slow-growing tumors or in patients for which other treatment types may be too toxic. Hormonal therapy is well tolerated and has response rates ranging from 9 to 33%. Hormonal treatment options take advantage of the estrogen-dependent molecular pathways in endometrial cancers. Current options for hormonal therapies include progesterone therapy (medroxyprogesterone acetate and megestrol acetate) as a single agent or in combination and agents that target the estrogen pathway. Aromatase inhibitors have had modest single-agent activity, but synergistic effects have been found when used in combination with targeted therapy including mTOR inhibitors and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. Molecular profiling of endometrial cancers has begun to help individualize treatments. This review will report on existing data and ongoing trials investigating novel hormonal therapy agents.
Integrated Analysis of N1-Methyladenosine Methylation Regulators-Related lncRNAs in Hepatocellular Carcinoma
Authors: Song Danjun , Wang Xi , Wang Yining , Liang Weiren , Luo Jun , Zheng Jiaping , Zhu Kai
Published: March 2023

N1-methyladenosine (m1A) and long non-coding RNAs (lncRNAs) play significant roles in tumor progression in hepatocellular carcinoma (HCC). However, their association with HCC is still unclear. In this study, lncRNAs related to m1A were extracted from the mRNA expression matrix in The Cancer Genome Atlas (TCGA) database. Five m1A-related lncRNAs (AL031985.3, NRAV, WAC-AS1, AC026412.3, and AC099850.4) were identified based on lasso Cox regression and they generated a prognostic signature of HCC. The prognostic signature was identified as an independent prognosis factor in HCC patients. Moreover, the prognostic signature achieved better performance than TP53 mutation status or tumor mutational burden (TMB) scores in the stratification of patient survival. The immune landscape indicated that most immune checkpoint genes and immune cells were distributed differently between both risk groups. A higher IC50 of chemotherapeutics (sorafenib, nilotinib, sunitinib, and gefitinib) was observed in the high-risk group, and a lower IC50 of gemcitabine in the low-risk group, suggesting the potential of the prognostic signature in chemosensitivity. In addition, fifty-five potential small molecular drugs were found based on drug sensitivity and NRAV expression. Together, five m1A-related lncRNAs generated a prognostic signature that could be a promising prognostic prediction approach and therapeutic response assessment tool for HCC patients.
Genomic Interplay between Neoneurogenesis and Neoangiogenesis in Carcinogenesis: Therapeutic Interventions
Authors: Dlamini Zodwa , Khanyile Richard , Molefi Thulo , Damane Botle Precious , Bates David Owen , Hull Rodney
Published: March 2023

Angiogenesis, the generation of new blood vessels, is one of the hallmarks of cancer. The growing tumor requires nutrients and oxygen. Recent evidence has shown that tumors release signals to attract new nerve fibers and stimulate the growth of new nerve fibers. Neurogenesis, neural extension, and axonogenesis assist in the migration of cancer cells. Cancer cells can use both blood vessels and nerve fibers as routes for cells to move along. In this way, neurogenesis and angiogenesis both contribute to cancer metastasis. As a result, tumor-induced neurogenesis joins angiogenesis and immunosuppression as aberrant processes that are exacerbated within the tumor microenvironment. The relationship between these processes contributes to cancer development and progression. The interplay between these systems is brought about by cytokines, neurotransmitters, and neuromodulators, which activate signaling pathways that are common to angiogenesis and the nervous tissue. These include the AKT signaling pathways, the MAPK pathway, and the Ras signaling pathway. These processes also both require the remodeling of tissues. The interplay of these processes in cancer provides the opportunity to develop novel therapies that can be used to target these processes.
Adoptive Cell Therapy in Hepatocellular Carcinoma: A Review of Clinical Trials
Authors: Ozer Muhammet , Goksu Suleyman Yasin , Akagunduz Baran , George Andrew , Sahin Ilyas
Published: March 2023

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Immune checkpoint inhibitors (ICIs) have become the new reference standard in first-line HCC treatment, replacing tyrosine kinase inhibitors (TKIs) such as sorafenib. Many clinical trials with different combinations are already in development to validate novel immunotherapies for the treatment of patients with HCC. Adoptive cell therapy (ACT), also known as cellular immunotherapy, with chimeric antigen receptors (CAR) or gene-modified T cells expressing novel T cell receptors (TCR) may represent a promising alternative approach to modify the immune system to recognize tumor cells with better clinical outcomes. In this review, we briefly discuss the overview of ACT as a promising treatment modality in HCC, along with recent updates of ongoing clinical trials.
Best Practices for Providing Patient-Centered Tele-Palliative Care to Cancer Patients
Authors: Aldana Grecia Lined , Evoh Onyinyechi Vanessa , Reddy Akhila
Published: March 2023

Cancer patients receiving palliative care may face significant challenges in attending outpatient appointments. Patients on controlled substances such as opioids require frequent visits and often rely on assistive devices and/or a caregiver to accompany them to these visits. In addition, pain, fatigue, and shortness of breath may magnify the challenges associated with in-person visits. The rapid adoption of telemedicine in response to the COVID-19 pandemic has proven to be highly beneficial for advanced cancer patients and caregivers. The hurried COVID-19-related implementation of telemedicine is now evolving into a permanent platform for providing palliative care. This review will focus on the best practices and recommendations to deliver high-quality, interdisciplinary tele-palliative care.
The FEDRA Longitudinal Study: Repeated Volumetric Breast Density Measures and Breast Cancer Risk
Authors: Masala Giovanna , Assedi Melania , Bendinelli Benedetta , Pastore Elisa , Gilio Maria Antonietta , Mazzalupo Vincenzo , Querci Andrea , Fontana Miriam , Duroni Giacomo , Facchini Luigi , Saieva Calogero , Palli Domenico , Ambrogetti Daniela , Caini Saverio
Published: March 2023

Mammographic breast density (MBD) is a strong independent risk factor for breast cancer (BC). We investigated the association between volumetric MBD measures, their changes over time, and BC risk in a cohort of women participating in the FEDRA (Florence-EPIC Digital mammographic density and breast cancer Risk Assessment) study. The study was carried out among 6148 women with repeated MBD measures from full-field digital mammograms and repeated information on lifestyle habits, reproductive history, and anthropometry. The association between MBD measures (modeled as time-dependent covariates), their relative annual changes, and BC risk were evaluated by adjusted Cox models. During an average of 7.8 years of follow-up, 262 BC cases were identified. BC risk was directly associated with standard deviation increments of volumetric percent density (VPD, HR 1.37, 95%CI 1.22–1.54) and dense volume (DV, HR 1.29, 95%CI 1.18–1.41). An inverse association emerged with non-dense volume (NDV, HR 0.82, 95%CI 0.69–0.98). No significant associations emerged between annual changes in VPD, DV, NDV, and BC risk. Higher values of MBD measures, modeled as time-dependent covariates, were positively associated with increased BC risk, while an inverse association was evident for increasing NDV. No effect of annual changes in MBD emerged.
Impact of a Training Program on Oncology Nurses’ Confidence in the Provision of Self-Management Support and 5As Behavioral Counseling Skills
Authors: Howell Doris , McGowan Patrick , Bryant-Lukosius Denise , Kirkby Ryan , Powis Melanie , Sherifali Diana , Kukreti Vishal , Rask Sara , Krzyzanowska Monica K.
Published: March 2023

Background: Cancer patients and their families play a central role in the self-management of the medical, emotional, and lifestyle consequences of cancer. Nurses with training in self-management support can enable cancer patients to better manage the effects of cancer and treatment. Methods: As part of a randomized controlled trial, we developed a training program to build nurses’ confidence in the provision of self-management support (SMS). The SMS skills taught were adapted from the Stanford Peer Support training programs and embedded within the 5As (Assess, Advise, Agree, Assist, and Arrange) behavioral counseling process. We evaluated the impact of the training program on oncology nurses’ and coaches’ confidence using a Student’s t-test for paired samples in a nonrandomized, one-group pre/postsurvey. Results: Participants were experienced oncology nurses from three participating cancer centers. A two-tailed Student’s t-test for paired samples showed a significant improvement in nurses’ confidence for the 15 SMS microskills targeted in the training between the pretest and post-test as follows: for Center 1, a mean difference of 0.79 (t = 7.18, p ≤ 0.00001); for Center 2, a mean difference of 0.73 (t = 8.4, p ≤ 0.00001); for Center 3, a mean difference of 1.57 (t = 11.45, p ≤ 0.00001); and for coaches, a mean difference of 0.52 (t = 7.6, p ≤ 0.00001). Conclusions: Our training program improved oncology staff nurses’ and cancer coaches’ confidence in 15 SMS microskills and has potential for SMS training of nurses in routine care.
Laparoscopic Microwave Ablation: Which Technologies Improve the Results
Authors: Santambrogio Roberto , Vertemati Maurizio , Barabino Matteo , Zappa Marco Antonio
Published: March 2023

Liver resection is the best treatment for hepatocellular carcinoma (HCC) when resectable. Unfortunately, many patients with HCC cannot undergo liver resection. Percutaneous thermoablation represents a valid alternative for inoperable neoplasms and for small HCCs, but it is not always possible to accomplish it. In cases where the percutaneous approach is not feasible (not a visible lesion or in hazardous locations), laparoscopic thermoablation may be indicated. HCC diagnosis is commonly obtained from imaging modalities, such as CT and MRI, However, the interpretation of radiological images, which have a two-dimensional appearance, during the surgical procedure and in particular during laparoscopy, can be very difficult in many cases for the surgeon who has to treat the tumor in a three-dimensional environment. In recent years, more technologies have helped surgeons to improve the results after ablative treatments. The three-dimensional reconstruction of the radiological images has allowed the surgeon to assess the exact position of the tumor both before the surgery (virtual reality) and during the surgery with immersive techniques (augmented reality). Furthermore, indocyanine green (ICG) fluorescence imaging seems to be a valid tool to enhance the precision of laparoscopic thermoablation. Finally, the association with laparoscopic ultrasound with contrast media could improve the localization and characteristics of tumor lesions. This article describes the use of hepatic three-dimensional modeling, ICG fluorescence imaging and laparoscopic ultrasound examination, convenient for improving the preoperative surgical preparation for personalized laparoscopic approach.
Efficacy of Antibodies Targeting TfR1 in Xenograft Mouse Models of AIDS-Related Non-Hodgkin Lymphoma
Authors: Daniels-Wells Tracy R. , Candelaria Pierre V. , Kranz Emiko , Wen Jing , Wang Lan , Kamata Masakazu , Almagro Juan C. , Martínez-Maza Otoniel , Penichet Manuel L.
Published: March 2023

Transferrin receptor 1 (TfR1), also known as CD71, is a transmembrane protein involved in the cellular uptake of iron and the regulation of cell growth. This receptor is expressed at low levels on a variety of normal cells, but is upregulated on cells with a high rate of proliferation, including malignant cells and activated immune cells. Infection with the human immunodeficiency virus (HIV) leads to the chronic activation of B cells, resulting in high expression of TfR1, B-cell dysfunction, and ultimately the development of acquired immunodeficiency syndrome-related B-cell non-Hodgkin lymphoma (AIDS-NHL). Importantly, TfR1 expression is correlated with the stage and prognosis of NHL. Thus, it is a meaningful target for antibody-based NHL therapy. We previously developed a mouse/human chimeric IgG3 specific for TfR1 (ch128.1/IgG3) and showed that this antibody exhibits antitumor activity in an in vivo model of AIDS-NHL using NOD-SCID mice challenged intraperitoneally with 2F7 human Burkitt lymphoma (BL) cells that harbor the Epstein-Barr virus (EBV). We have also developed an IgG1 version of ch128.1 that shows significant antitumor activity in SCID-Beige mouse models of disseminated multiple myeloma, another B-cell malignancy. Here, we aim to explore the utility of ch128.1/IgG1 and its humanized version (hu128.1) in mouse models of AIDS-NHL. To accomplish this goal, we used the 2F7 cell line variant 2F7-BR44, which is more aggressive than the parental cell line and forms metastases in the brain of mice after systemic (intravenous) administration. We also used the human BL cell line JB, which in contrast to 2F7, is EBV-negative, allowing us to study both EBV-infected and non-infected NHL tumors. Treatment with ch128.1/IgG1 or hu128.1 of SCID-Beige mice challenged locally (subcutaneously) with 2F7-BR44 or JB cells results in significant antitumor activity against different stages of disease. Treatment of mice challenged systemically (intravenously) with either 2F7-BR44 or JB cells also showed significant antitumor activity, including long-term survival. Taken together, our results suggest that targeting TfR1 with antibodies, such as ch128.1/IgG1 or hu128.1, has potential as an effective therapy for AIDS-NHL.
Endothelial Progenitor Cells Promote Osteosarcoma Progression and Invasiveness via AKT/PI3K Signaling
Authors: Doppelt-Flikshtain Ofri , Younis Amin , Tamari Tal , Ginesin Ofir , Shentzer-Kutiel Talia , Nikomarov David , Bar-Sela Gil , Coyac Benjamin R. , Assaraf Yehuda G. , Zigdon-Giladi Hadar
Published: March 2023

Background: Osteosarcoma (OS) mortality is attributed to lung metastases. Endothelial progenitor cells (EPCs) mediate the angiogenic switch in several cancers. The spatial proximity between EPCs and OS in the bone led to the hypothesis that EPCs-osteosarcoma interactions may possibly promote OS progression and aggressiveness. Methods: A PI3K inhibitor, Bevacizumab (an anti-VEGF-A antibody), and an anti-FGF2 antibody were added to the EPCs’ conditioned medium (EPC-CM), and their impacts on OS cell (U2-OS and 143B) proliferation, migration, invasion, MMP9 expression, and AKT phosphorylation were determined. The autocrine role of VEGF-A was assessed using Bevacizumab treatment and VEGF-A silencing in OS cells. Toward this end, an orthotopic mouse OS model was established. Mouse and human tumors were immunolabeled with antibodies to the abovementioned factors. Results: EPC-CM enhanced osteosarcoma MMP9 expression, invasiveness, and migration via the PI3K/AKT pathway. The addition of Bevacizumab and an anti-FGF2 antibody to the EPC-CM diminished OS cell migration. The autocrine role of VEGF-A was assessed using Bevacizumab and VEGF-A silencing in OS cells, resulting in decreased AKT phosphorylation and, consequently, diminished invasiveness and migration. Consistently, OS xenografts in mice displayed high VEGF-A and FGF2 levels. Remarkably, lung metastasis specimens derived from OS patients exhibited marked immunolabeling of CD31, VEGF-A, and FGF2. Conclusions: EPCs promote OS progression not only by physically incorporating into blood vessels, but also by secreting cytokines, which act via paracrine signaling. EPCs induced in vitro MMP9 overexpression, invasion, and migration. Additional animal studies are warranted to further expand these results. These findings may pave the way toward the development of novel EPCs-targeted therapeutics aimed at blocking OS metastasis.
Sonocatalytic Degradation of Chrysoidine R Dye Using Ultrasonically Synthesized NiFe2O4 Catalyst
Authors: Gote Yogesh M. , Sinhmar Pankaj S. , Gogate Parag R.
Published: March 2023

The novel ultrasound-assisted co-precipitation method was successfully applied for the synthesis of the NiFe2O4 catalyst, which offered the advantages of lower particle size and better crystalline structure without affecting the phase planes. Furthermore, the efficacy of synthesized catalysts was evaluated using ultrasound-assisted catalytic degradation of Chrysoidine R dye. The study was designed to evaluate the effect of different parameters, such as pH, duty cycle, power output, and catalyst loading on Chrysoidine R dye degradation using a 5 wt% NiFe2O4 catalyst synthesized ultrasonically. At the optimized condition of 120 W ultrasonic power, 70% duty cycle, 3 pH, 0.5 g/L catalyst loading, and 160 min of reaction time, the best degradation of 45.01% was obtained. At similar conditions, the conventionally synthesized catalyst resulted in about 15% less degradation. Chrysoidine R dye degradation was observed to follow second-order kinetics. To accelerate the degradation, studies were performed using hydrogen peroxide at various loadings where it was elucidated that optimum use of 75 ppm loading showed the maximum degradation of 92.83%, signifying the important role of the co-oxidant in ultrasound-assisted catalytic degradation of Chrysoidine R dye. Overall, the present study clearly demonstrated the potential benefits of ultrasound in catalyst synthesis as well as in catalytic degradation.
Facile Construction of Intramolecular g-CN-PTCDA Donor-Acceptor System for Efficient CO2 Photoreduction
Authors: Wei Jiajia , Chen Xing , Ren Xitong , Tian Shufang , Bai Feng
Published: March 2023

Due to the different electron affinity, the construction of a donor-acceptor (DA) system in the graphitic carbon nitride (g-CN) matrix is an attractive tactic to accelerate photo-induced electron-holes separation, and then further elevate its photocatalytic performance. In this work, perylene tetracarboxylic dianhydride (PTCDA) with magnificent electron affinity and excellent thermal stability was chosen to copolymerize with urea via facile one-pot thermal copolymerization to fabricate g-CN-PTCDA equipped with DA structures. The specific surface area of g-CN-PTCDA would be enlarged and the visible light absorption range would be broadened simultaneously when adopting this copolymerization strategy. A series of characterizations such as electron paramagnetic resonance (EPR), steady and transient photoluminescence spectra (PL), electrochemical impedance spectroscopy (EIS), and photocurrent tests combined with computational simulation confirmed the charge separation and transfer efficiency dramatically improved due to the DA structures construction. When 0.25% wt PTCDA was introduced, the CO evolution rate was nearly 23 times than that of pristine g-CN. The CO evolution rate could reach up to 87.2 μmol g−1 h−1 when certain Co2+ was added as co-catalytic centers. Meanwhile, g-CN-1 mg PTCDA-Co exhibited excellent long-term stability and recyclability as a heterogeneous photocatalyst. This research may shed light on designing more effective DA structures for solar-to-energy conversion by CO2 reduction.
Immobilization of Alpha Acetolactate Decarboxylase in Hybrid Gelatin/Alginate Support for Application to Reduce Diacetyl Off-Flavor in Beer
Authors: Costa Gustavo P. , Queiroz Leonardo B. , Manfroi Vitor , Rodrigues Rafael C. , Hertz Plinho F.
Published: March 2023

Beer production is the largest among alcoholic beverages. Its production process is complex and demands several steps. Lager beers commonly present an off-flavor of butter that is due to the presence of diacetyl, and to avoid such a problem, a long period of maturation (3–5 weeks) is required. Another way is the application of (α-acetolactate decarboxylase) ALDC to accelerate the process. The objectives of the present work were to develop a low-cost support using gelatin, a residue from capsules from the nutraceutical industry, to immobilize the ALDC enzyme. For this, the yield, efficiency and activity recovered, and the stability of free and immobilized enzymes at different temperatures and pH were evaluated. To evaluate the capacity of immobilized enzymes when applied directly to beer and their operational stability, three concentrations of glutaraldehyde (1%, 2.5% and 5%) were tested in distilled water as a cross-linking agent. The best results obtained were 95.6%, 27.0% and 23.6%, respectively, for yield, efficiency and activity recovery. Immobilization provided a high activity over a wide pH range. The immobilized enzyme showed greater stability at temperatures of 50 and 60 °C. The immobilized derivative showed adequate reuse capacity, and its dehydrated form had excellent activity after long periods of storage.