bluuebunny/crossref_metadata_2025 huggingface dataset:
An Application of wt-Distances to Characterize Complete b-Metric Spaces
Authors: Romaguera Salvador
Published: January 2023

The notion of wt-distance, introduced by Hussain et al. provides a natural generalization to the b-metric framework of the well-known and fruitful concept of w-distance, initiated by Kada et al. Since then, several authors have obtained fixed point theorems for complete b-metric spaces with the help of wt-distances. In this note, we generalize the b-metric version of the celebrated Matkowski fixed point theorem, stated by Czerwik, by replacing the involved b-metric with any wt-distance on the corresponding complete b-metric space. From this result, we derive characterizations of complete b-metric spaces that constitute full generalizations of both a prominent characterization of metric completeness due to Suzuki and Takahashi, and the classical characterization of metric completeness obtained by Hu.
An Insoluble Amino-Functionalized Hexaazatriphenylene as Stable Organic Cathode in Lithium-Ion Batteries
Authors: Xu Pengfei , Jin Xiao , Zhang Biao , Wang Xin , Liu Dong
Published: January 2023

Organic electrode materials have received increasing attention in rechargeable batteries due to their earth abundance and variable structures. However, the practical application of most organic electrode materials is limited by the high solubility in the electrolyte. Herein, an insoluble amino-functionalized hexaazatriphenylene (defined as HATN-[NH2]3) in the electrolyte is developed as stable organic cathode material for lithium-ion batteries (LIBs). The resultant HATN-[NH2]3 electrode achieves a high reversible capacity of 192.5 mAh g−1 at a current density of 0.05 A g−1. Remarkably, the electrode exhibits almost no capacity fade after 500 cycles at 0.5 A g−1. The high stability can be ascribed to insoluble property caused by hydrogen bonds between HATN-[NH2]3 molecules. Moreover, density functional theory calculations suggest that amino functionalization can reduce the band gap of HATN, in favor of improved conductivity and thus enhanced rate performance. This work offers a simple but efficient strategy to develop stable organic electrode materials in LIBs and beyond.
A New Conformal Penetrating Heating Strategy for Atherosclerotic Plaque
Authors: Wang Hongying , Zhao Shiqing , Zou Jincheng , Zhang Aili
Published: January 2023

(1) Background: A combination of radiofrequency (RF) volumetric heating and convection cooling has been proposed to realize plaque ablation while protecting the endothelial layer. However, the depth of the plaque and the thickness of the endothelial layer vary in different atherosclerotic lesions. Current techniques cannot be used to achieve penetrating heating for atherosclerosis with two targets (the specified protection depth and the ablation depth). (2) Methods: A tissue-mimicking phantom heating experiment simulating atherosclerotic plaque ablation was conducted to investigate the effects of the control parameters, the target temperature (Ttarget), the cooling water temperature (Tf), and the cooling water velocity (Vf). To further quantitatively analyze and evaluate the ablation depth and the protection depth of the control parameters, a three-dimensional model was established. In addition, a conformal penetrating heating strategy was proposed based on the numerical results. (3) Results: It was found that Ttarget and Tf were factors that regulated the ablation results, and the temperatures of the plaques varied linearly with Ttarget or Tf. The simulation results showed that the ablation depth increased with the Ttarget while the protection depth decreased correspondently. This relationship reversed with the Tf. When the two parameters Ttarget and Tfwere controlled together, the ablation depth was 0.47 mm–1.43 mm and the protection depth was 0 mm–0.26 mm within 2 min of heating. (4) Conclusions: With the proposed control algorithm, the requirements of both the ablation depth and the endothelium protection depth can be met for most plaques through the simultaneous control of Ttarget and Tf.
Intra-Population Alteration on Voltinism of Asian Corn Borer in Response to Climate Warming
Authors: Liu Kaiqiang , Wang Zhenying , Zhang Tiantao , He Kanglai
Published: January 2023

The Asian corn borer (ACB) Ostrinia furnacalis (Guenée) can occur in one to seven generations annually from cool (48°00′ N) to warm (18°10′ N) region of corn cultivation in China. Although ACB is commonly known as a facultative larval diapause insect, the co-existence of various voltinism suggests that intra-population variation may have evolved for the nature of diapause, i.e., voltinism plasticity. Here, we conducted recurrent selection efforts to establish three strains of, respectively, univoltine (with obligate diapause), multivoltine (with facultative diapause), and non-diapausing ACB under various temperature and photoperiod environments. The univoltine (Lu) strain has evolved a stable univoltinism under a diapause suppressing condition (16 h daylength at 28 °C), with the diapause incidence constantly over 80% after three generations of selection. The multivoltine strain (Lm) under the high temperature (28 °C) was shown to have a typical facultative diapause induced by a range of short-day lengths (11–13.5 h). Diapause incidence was constantly <2.6% under the long day length (16 h) when the temperature was from 18 to 28 °C, i.e., low temperature could not enhance the diapause response in the Lm strain. However, the development was prolonged from 14.2 ± 0.3 d to 46.0 ± 0.8 d when the temperature was reduced from 28 °C to 18 °C. The majority (94.4%) of the developed Ln strain still maintained the non-diapausing nature under a diapause enhancing condition, i.e., a short (13 h) daylength at a low temperature (22 °C). Lm and Ln were able to complete their second generation in Heihe (50°14′ N) if the first-generation moth oviposits before 18 June. The study suggests that ACB has evolutionary intra-population variation in voltinism. Under the climate change scenario warmer spring and summer might affect the proportion of sympatric voltine biotype populations that evolve toward being multivoltine.
Transcriptomic Analysis of Hepatitis B Infected Liver for Prediction of Hepatocellular Carcinoma
Authors: Karaoglu Diren Arda , Uner Meral , Simsek Cem , Gure Ali Osmay , Demirkol-Canli Secil
Published: January 2023

Hepatocellular cancer (HCC) is a leading cause of cancer-related mortality worldwide, and chronic hepatitis B virus infection (CHB) has been a major risk factor for HCC development. The pathogenesis of HBV-related HCC has been a major focus revealing the interplay of a multitude of intracellular signaling pathways, yet the precise mechanisms and their implementations to clinical practice remain to be elucidated. This study utilizes publicly available transcriptomic data from the livers of CHB patients in order to identify a population with a higher risk of malignant transformation. We report the identification of a novel list of genes (PCM1) which can generate clear transcriptomic sub-groups among HBV-infected livers. PCM1 includes genes related to cell cycle activity and liver cancer development. In addition, markers of inflammation, M1 macrophages and gamma delta T cell infiltration are present within the signature. Genes within PCM1 are also able to differentiate HCC from normal liver, and some genes within the signature are associated with poor prognosis of HCC at the mRNA level. The analysis of the immunohistochemical stainings validated that proteins coded by a group of PCM1 genes were overexpressed in liver cancer, while minimal or no expression was detected in normal liver. Altogether, our findings suggest that PCM1 can be developed into a clinically applicable method to identify CHB patients with a higher risk of HCC development.
Selection and Evaluation of mRNA and miRNA Reference Genes for Expression Studies (qPCR) in Archived Formalin-Fixed and Paraffin-Embedded (FFPE) Colon Samples of DSS-Induced Colitis Mouse Model
Authors: Unkovič Ana , Boštjančič Emanuela , Belič Aleš , Perše Martina
Published: January 2023

The choice of appropriate reference genes is essential for correctly interpreting qPCR data and results. However, the majority of animal studies use a single reference gene without any prior evaluation. Therefore, many qPCR results from rodent studies can be misleading, affecting not only reproducibility but also translatability. In this study, the expression stability of reference genes for mRNA and miRNA in archived FFPE samples of 117 C57BL/6JOlaHsd mice (males and females) from 9 colitis experiments (dextran sulfate sodium; DSS) were evaluated and their expression analysis was performed. In addition, we investigated whether normalization reduced/neutralized the influence of inter/intra-experimental factors which we systematically included in the study. Two statistical algorithms (NormFinder and Bestkeeper) were used to determine the stability of reference genes. Multivariate analysis was made to evaluate the influence of normalization with different reference genes on target gene expression in regard to inter/intra-experimental factors. Results show that archived FFPE samples are a reliable source of RNA and imply that the FFPE procedure does not change the ranking of stability of reference genes obtained in fresh tissues. Multivariate analysis showed that the histological picture is an important factor affecting the expression levels of target genes.
Identification of Driver Genes and miRNAs in Ovarian Cancer through an Integrated In-Silico Approach
Authors: Beg Anam , Parveen Rafat , Fouad Hassan , Yahia M. E. , Hassanein Azza S.
Published: January 2023

Ovarian cancer is the eighth-most common cancer in women and has the highest rate of death among all gynecological malignancies in the Western world. Increasing evidence shows that miRNAs are connected to the progression of ovarian cancer. In the current study, we focus on the identification of miRNA and its associated genes that are responsible for the early prognosis of patients with ovarian cancer. The microarray dataset GSE119055 used in this study was retrieved via the publicly available GEO database by NCBI for the analysis of DEGs. The miRNA GSE119055 dataset includes six ovarian carcinoma samples along with three healthy/primary samples. In our study, DEM analysis of ovarian carcinoma and healthy subjects was performed using R Software to transform and normalize all transcriptomic data along with packages from Bioconductor. Results: We identified miRNA and its associated hub genes from the samples of ovarian cancer. We discovered the top five upregulated miRNAs (hsa-miR-130b-3p, hsa-miR-18a-5p, hsa-miR-182-5p, hsa-miR-187-3p, and hsa-miR-378a-3p) and the top five downregulated miRNAs (hsa-miR-501-3p, hsa-miR-4324, hsa-miR-500a-3p, hsa-miR-1271-5p, and hsa-miR-660-5p) from the network and their associated genes, which include seven common genes (SCN2A, BCL2, MAF, ZNF532, CADM1, ELAVL2, and ESRRG) that were considered hub genes for the downregulated network. Similarly, for upregulated miRNAs we found two hub genes (PRKACB and TAOK1).
Ultra-Rare Variants Identify Biological Pathways and Candidate Genes in the Pathobiology of Non-Syndromic Cleft Palate Only
Authors: Iovino Emanuela , Scapoli Luca , Palmieri Annalisa , Sgarzani Rossella , Nouri Nayereh , Pellati Agnese , Carinci Francesco , Seri Marco , Pippucci Tommaso , Martinelli Marcella
Published: January 2023

In recent decades, many efforts have been made to elucidate the genetic causes of non-syndromic cleft palate (nsCPO), a complex congenital disease caused by the interaction of several genetic and environmental factors. Since genome-wide association studies have evidenced a minor contribution of common polymorphisms in nsCPO inheritance, we used whole exome sequencing data to explore the role of ultra-rare variants in this study. In a cohort of 35 nsCPO cases and 38 controls, we performed a gene set enrichment analysis (GSEA) and a hypergeometric test for assessing significant overlap between genes implicated in nsCPO pathobiology and genes enriched in ultra-rare variants in our cohort. GSEA highlighted an enrichment of ultra-rare variants in genes principally belonging to cytoskeletal protein binding pathway (Probability Density Function corrected p-value = 1.57 × 10−4); protein-containing complex binding pathway (p-value = 1.06 × 10−2); cell adhesion molecule binding pathway (p-value = 1.24 × 10−2); ECM-receptor interaction pathway (p-value = 1.69 × 10−2); and in the Integrin signaling pathway (p-value = 1.28 × 10−2). Two genes implicated in nsCPO pathobiology, namely COL2A1 and GLI3, ranked among the genes (n = 34) with nominal enrichment in the ultra-rare variant collapsing analysis (Fisher’s exact test p-value < 0.05). These genes were also part of an independent list of genes highly relevant to nsCPO biology (n = 25). Significant overlap between the two sets of genes (hypergeometric test p-value = 5.86 × 10−3) indicated that enriched genes are likely to be implicated in physiological palate development and/or the pathological processes of oral clefting. In conclusion, ultra-rare variants collectively impinge on biological pathways crucial to nsCPO pathobiology and point to candidate genes that may contribute to the individual risk of disease. Sequencing can be an effective approach to identify candidate genes and pathways for nsCPO.
Adipose Tissue and Adipose-Tissue-Derived Cell Therapies for the Treatment of the Face and Hands of Patients Suffering from Systemic Sclerosis
Authors: Coulange Zavarro Anouck , Velier Mélanie , Arcani Robin , Abellan Lopez Maxime , Simoncini Stéphanie , Benyamine Audrey , Gomes De Pinho Quentin , Coatmeur Raphael , Wang Jiucun , Xia Jingjing , Barone Ludovica , Casanova Dominique , Dignat-George Françoise , Sabatier Florence , Granel Brigitte , Magalon Jérémy , Daumas Aurélie
Published: January 2023

Adipose tissue is recognized as a valuable source of cells with angiogenic, immunomodulatory, reparative and antifibrotic properties and emerged as a therapeutic alternative for the regeneration and repair of damaged tissues. The use of adipose-tissue-based therapy is expanding in autoimmune diseases, particularly in Systemic Sclerosis (SSc), a disease in which hands and face are severely affected, leading to disability and a decrease in quality of life. Combining the advantage of an abundant supply of fat tissue and a high abundance of stem/stromal cells, fat grafting and adipose tissue-derived cell-based therapies are attractive therapeutic options in SSc. This review aims to synthesize the evidence to determine the effects of the use of these biological products for face and hands treatment in the context of SSc. This highlights several points: the need to use relevant effectiveness criteria taking into account the clinical heterogeneity of SSc in order to facilitate assessment and comparison of innovative therapies; second, it reveals some impacts of the disease on fat-grafting success; third, an important heterogeneity was noticed regarding the manufacturing of the adipose-derived products and lastly, it shows a lack of robust evidence from controlled trials comparing adipose-derived products with standard care.
Cardiac Resynchronization Therapy and Hypertrophic Cardiomyopathy: A Comprehensive Review
Authors: Radu Andrei , Cojocaru Cosmin , Onciul Sebastian , Scarlatescu Alina , Zlibut Alexandru , Nastasa Alexandrina , Dorobantu Maria
Published: January 2023

Hypertrophic cardiomyopathy (HCM) is an inherited primary myocardial disease characterized by asymmetrical/symmetrical left ventricle (LV) hypertrophy, with or without LV outflow tract (LVOT) dynamic obstruction, and poor prognosis. Cardiac resynchronization therapy (CRT) has emerged as a minimally invasive tool for patients with heart failure (HF) with decreased LV ejection fraction (LVEF) and prolonged QRS duration of over 120 ms with or without left bundle branch block (LBBB). Several HCM patients are at risk of developing LBBB because of disease progression or secondary to septal myomectomy, while others might develop HF with decreased LVEF, alleged end-stage/dilated HCM, especially those with thin myofilament mutations. Several studies have shown that patients with myectomy-induced LBBB might benefit from left bundle branch pacing or CRT to relieve symptoms, improve exercise capacity, and increase LVEF. Otherwise, patients with end-stage/dilated HCM and prolonged QRS interval could gain from CRT in terms of NYHA class improvement, LV systolic performance increase and, to some degree, LV reverse remodeling. Moreover, several electrical and imaging parameters might aid proper selection and stratification of HCM patients to benefit from CRT. Nonetheless, current available data are scarce and further studies are still required to accurately clarify the view. This review reassesses the importance of CRT in patients with HCM based on current research by contrasting and contextualizing data from various published studies.
Hand Grip Strength Relative to Waist Circumference as a Means to Identify Men and Women Possessing Intact Mobility in a Cohort of Older Adults with Type 2 Diabetes
Authors: Kis Ofer S. , Buch Assaf , Eldor Roy , Moran Daniel S.
Published: January 2023

Possessing intact mobility in older adults assures their continued independence. The early identification of reduced mobility in older adults with type 2 diabetes (T2DM) is paramount for preventing their future physical deterioration. Hand grip strength (HGS), relative to body size, is associated with mobility in older T2DM patients. This study aims to identify an HGS index that best identifies mobilityintact older T2DM patients, along with its optimal cut-off point. The baseline data are from a cohort of 122 older T2DM patients (59% women) (mean age of 70.2 ± 4.4 years). Three mobility tests encompassing three main mobility domains were measured, including usual gait speed (UGS), timed up and go (TUG), and a two-minute walk test (2MWT). Passing scores were defined as those either above the established cut-off points or above the 25th percentile of population norms. Passing all three tests was considered as possessing intact mobility. Receiver operating characteristic (ROC) curves of the most relevant HGS indices were constructed to determine the area under the curve (AUC) that best identifies patients with intact mobility. In a sample of 122 older adults with T2DM, 63.9% of women and 60% of men were found to possess intact mobility. HGS relative to waist circumference (WC) was found to have the strongest association with intact mobility, presenting the highest AUC in both men (0.78) and women (0.72) for discriminating mobility status, with an optimal cut-off of 0.355 (kg/cm) and 0.245 (kg/cm) in men and women, respectively. HGS relative to WC best differentiated between mobility-intact older adults with T2DM and those with mobility limitations, especially in men. Using HGS/WC as a simple and safe screening mode for mobility in a clinical setting could potentially identify older patients with T2DM that require therapeutic interventions.
Lower Extremity Arterial Disease in Type 2 Diabetes Mellitus: Metformin Inhibits Femoral Artery Ultrastructural Alterations as well as Vascular Tissue Levels of AGEs/ET-1 Axis-Mediated Inflammation and Modulation of Vascular iNOS and eNOS Expression
Authors: Shati Ayed A. , Maarouf Amro , Dawood Amal F. , Bayoumy Nervana M. , Alqahtani Youssef A. , A. Eid Refaat , Alqahtani Saeed M. , Abd Ellatif Mohamed , Al-Ani Bahjat , Albawardi Alia
Published: January 2023

Lower extremity arterial disease (LEAD) is a major risk factor for amputation in diabetic patients. The advanced glycation end products (AGEs)/endothelin-1 (ET-1)/nitric oxide synthase (NOS) axis-mediated femoral artery injury with and without metformin has not been previously investigated. Type 2 diabetes mellitus (T2DM) was established in rats, with another group of rats treated for two weeks with 200 mg/kg metformin, before being induced with T2DM. The latter cohort were continued on metformin until they were sacrificed at week 12. Femoral artery injury was established in the diabetic group as demonstrated by substantial alterations to the femoral artery ultrastructure, which importantly were ameliorated by metformin. In addition, diabetes caused a significant (p < 0.0001) upregulation of vascular tissue levels of AGEs, ET-1, and iNOS, as well as high blood levels of glycated haemoglobin, TNF-α, and dyslipidemia. All of these parameters were also significantly inhibited by metformin. Moreover, metformin treatment augmented arterial eNOS expression which had been inhibited by diabetes progression. Furthermore, a significant correlation was observed between femoral artery endothelial tissue damage and glycemia, AGEs, ET-1, TNF-α, and dyslipidemia. Thus, in a rat model of T2DM-induced LEAD, an association between femoral artery tissue damage and the AGEs/ET-1/inflammation/NOS/dyslipidemia axis was demonstrated, with metformin treatment demonstrating beneficial vascular protective effects.
CDC25C Protein Expression Correlates with Tumor Differentiation and Clinical Outcomes in Lung Adenocarcinoma
Authors: Stern Esther , Pines Guy , Lazar Li Or , Vainer Gilad W. , Beltran Nitzan , Dodi Omri , Gamaev Lika , Hikri Simon Ofir , Abraham Michal , Wald Hanna , Peled Amnon , Wald Ori
Published: January 2023

Given that, even after multimodal therapy, early-stage lung cancer (LC) often recurs, novel prognostic markers to help guide therapy are highly desired. The mRNA levels of cell division cycle 25C (CDC25C), a phosphatase that regulates G2/M cell cycle transition in malignant cells, correlate with poor clinical outcomes in lung adenocarcinoma (LUAD). However, whether CDC25C protein detected by immunohistochemistry can serve as a prognostic marker in LUAD is yet unknown. We stained an LC tissue array and a cohort of 61 LUAD tissue sections for CDC25C and searched for correlations between CDC25C staining score and the pathological characteristics of the tumors and the patients’ clinical outcomes. Clinical data were retrieved from our prospectively maintained departmental database. We found that high expression of CDC25C was predominant among poorly differentiated LUAD (p < 0.001) and in LUAD > 1cm (p < 0.05). Further, high expression of CDC25C was associated with reduced disease-free survival (p = 0.03, median follow-up of 39 months) and with a trend for reduced overall survival (p = 0.08). Therefore, high expression of CDC25C protein in LUAD is associated with aggressive histological features and with poor outcomes. Larger studies are required to further validate CDC25C as a prognostic marker in LUAD.
Relationship between Novel Elastography Techniques and Renal Fibrosis—Preliminary Experience in Patients with Chronic Glomerulonephritis
Authors: Maralescu Felix-Mihai , Vaduva Adrian , Schiller Adalbert , Petrica Ligia , Sporea Ioan , Popescu Alina , Sirli Roxana , Dema Alis , Bodea Madalina , Grosu Iulia , Bob Flaviu
Published: January 2023

Introduction: A renal biopsy represents the gold standard in the diagnosis, prognosis, and management of patients with glomerulonephritis. So far, non-invasive elastographic techniques have not confirmed their utility in replacing a biopsy; however, the new and improved software from Hologic Supersonic Mach 30 is a promising method for assessing the renal tissue’s stiffness and viscosity. We investigated whether this elastography technique could reveal renal tissue fibrosis in patients with chronic glomerulonephritis. Materials and methods: Two-dimensional-shear wave elastography (SWE) PLUS and viscosity plane-wave ultrasound (Vi PLUS) assessments were performed in 40 patients with chronic glomerulopathies before being referred for a renal biopsy. For each kidney, the mean values of five stiffness and viscosity measures were compared with the demographic, biological, and histopathological parameters of the patients. Results: In total, 26 men and 14 women with a mean age of 52.35 ± 15.54 years, a mean estimated glomerular filtration rate (eGFR) of 53.8 ± 35.49 mL/min/1.73m2, and a mean proteinuria of 6.39 ± 7.42 g/24 h were included after providing their informed consent. Out of 40 kidney biopsies, 2 were uninterpretable with inappropriate material and were divided into four subgroups based on their fibrosis percentage. Even though these elastography techniques were unable to differentiate between separate fibrosis stages, when predicting between the fibrosis and no-fibrosis group, we found a cut-off value of <20.77 kPa with the area under the curve (AUC) of 0.860, a p < 0.001 with 88.89% sensitivity, and a 75% specificity for the 2D SWE PLUS measures and a cut-off value of <2.8 Pa.s with an AUC of 0.792, a p < 0.001 with 94% sensitivity, and a 60% specificity for the Vi PLUS measures. We also found a cut-off value of <19.75 kPa for the 2D SWE PLUS measures (with an AUC of 0.789, p = 0.0001 with 100% sensitivity, and a 74.29% specificity) and a cut-off value of <1.28 Pa.s for the Vi PLUS measures (with an AUC 0.829, p = 0.0019 with 60% sensitivity, and a 94.29% specificity) differentiating between patients with over 40% fibrosis and those with under 40%. We also discovered a positive correlation between the glomerular filtration rate (eGFR) and 2D-SWE PLUS values (r = 0.7065, p < 0.0001) and Vi PLUS values (r = 0.3637, p < 0.0211). C reactive protein (CRP) correlates with the Vi PLUS measures (r = −0.3695, p = 0.0189) but not with the 2D SWE PLUS measures (r = −0.2431, p = 0.1306). Conclusion: Our findings indicate that this novel elastography method can distinguish between individuals with different stages of renal fibrosis, correlate with the renal function and inflammation, and are easy to use and reproducible, but further research is needed for them to be employed routinely in clinical practice.
In Vitro Evaluation of the Cytotoxic Potential of Thiosemicarbazide Coordinating Compounds in Hepatocyte Cell Culture
Authors: Pantea Valeriana , Cobzac Vitalie , Tagadiuc Olga , Palarie Victor , Gudumac Valentin
Published: January 2023

Cancer is a global medical problem and, despite research efforts in the field of tumor treatment, there is currently a shortage of specific anticancer drugs. Most anticancer drugs show significant side effects. The liver is the organ that has central functions in drug metabolism, being a major target of the harmful action of anticancer compounds. In this context, it is essential to evaluate the cytotoxic effects of potential anticancer substances. Therefore, hepatotoxicity and hepatocyte viability were determined in vitro to evaluate the action of seven new local thiosemicarbazide coordination compounds (CCT) on normal liver cells. Doxorubicin was used as a reference substance. The control group consisted of hepatocytes not exposed to CCT action. The cell viability of hepatocytes treated with CCT decreased significantly by 5–12% compared to the control, but was statistically significantly higher by 5–14% compared to doxorubicin, except after CMD-8 and CMT-67 influence, when it does not change. Thus, new local CCT had a selective effect on hepatocytes in vitro and were less hepatotoxic compared to doxorubicin, which may be the basis for further study of its potential in anticancer drugs.
An Ultra High Gain Converter for Driving HASEL Actuator Used in Soft Mobile Robots
Authors: Lodh Tirthasarathi , Le Hanh-Phuc
Published: January 2023

Soft robots have the potential to fundamentally change interactions between robots and the surrounding environment, and between robots and animals, and robots and humans in ways that today’s hard robots are incapable of doing. However, to realize this potential, soft robot actuators require extremely high voltage supplies of more than 4 kV. The electronics that can satisfy this need currently are either too large and bulky or unable to achieve the high power efficiency required for mobile systems. To meet this challenge, this paper conceptualizes, analyzes, designs, and validates a hardware prototype of an ultra-high gain (UHG) converter that can support extremely large conversion ratios up to ∼1000× to provide up to 5 kV output voltage from an input voltage of ∼5–10 V. This converter is demonstrated to be able to drive HASEL (Hydraulically Amplified Self-Healing Electrostatic) actuators, a promising candidate to realize future soft mobile robotic fishes, from an input voltage range of a 1-cell battery pack. The circuit topology employs a unique hybrid combination of a high-gain switched magnetic element (HGSME) and a diode and capacitor-based voltage multiplier rectifier (DCVMR) to enable compact magnetic elements, efficient soft-charging in all flying capacitors, and adjustable output voltage capability with simple duty-cycle modulation. Achieving an efficiency of 78.2% at 15 W output power, while providing 3.85 kV output from 8.5 V input, the proposed UGH converter proves to be a promising candidate for future untethered soft robots.
Porphyrin-Based Covalent Organic Frameworks with Donor-Acceptor Structure for Enhanced Peroxidase-like Activity as a Colorimetric Biosensing Platform
Authors: Wang Qian , Lv Liang , Chi Wenhao , Bai Yujiao , Gao Wenqing , Zhu Peihua , Yu Jinghua
Published: January 2023

Hydrogen peroxide (H2O2) and glucose play a key role in many cellular signaling pathways. The efficient and accurate in situ detection of H2O2 released from living cells has attracted extensive research interests. Herein, a new porphyrin-based porous covalent organic framework (TAP-COF) was fabricated via one-step condensation of 1,6,7,12-tetrachloroperylene tetracarboxylic acid dianhydride and 5,10,15,20-tetrakis (4-aminophenyl)porphyrin iron(III). The obtained TAP-COF has high surface areas, abundant surface catalytic active sites, and highly effective electron transport due to its precisely controllable donor–acceptor arrangement and 3D porous structure. Then, the new TAP-COF exhibited excellent peroxidase-like catalytic activity, which could effectively catalyze oxidation of the substrate 3,3′,5,5′-tetramethylbenzidine by H2O2 to produce a typical blue-colored reaction. On this basis, simple, rapid and selective colorimetric methods for in situ H2O2 detection were developed with the detection limit of 2.6 nM in the wide range of 0.01 to 200 μM. The colorimetric approach also could be used for in situ detection of H2O2 released from living MCF-7 cells. This portable sensor based on a COF nanozyme not only opens a new path for point-of-care testing, but also has potential applications in the field of cell biology and clinical diagnosis.
Bacterial Membrane Mimetics: From Biosensing to Disease Prevention and Treatment
Authors: Arya Sagar S. , Morsy Nada K. , Islayem Deema K. , Alkhatib Sarah A. , Pitsalidis Charalampos , Pappa Anna-Maria
Published: January 2023

Plasma membrane mimetics can potentially play a vital role in drug discovery and immunotherapy owing to the versatility to assemble facilely cellular membranes on surfaces and/or nanoparticles, allowing for direct assessment of drug/membrane interactions. Recently, bacterial membranes (BMs) have found widespread applications in biomedical research as antibiotic resistance is on the rise, and bacteria-associated infections have become one of the major causes of death worldwide. Over the last decade, BM research has greatly benefited from parallel advancements in nanotechnology and bioelectronics, resulting in multifaceted systems for a variety of sensing and drug discovery applications. As such, BMs coated on electroactive surfaces are a particularly promising label-free platform to investigate interfacial phenomena, as well as interactions with drugs at the first point of contact: the bacterial membrane. Another common approach suggests the use of lipid-coated nanoparticles as a drug carrier system for therapies for infectious diseases and cancer. Herein, we discuss emerging platforms that make use of BMs for biosensing, bioimaging, drug delivery/discovery, and immunotherapy, focusing on bacterial infections and cancer. Further, we detail the synthesis and characteristics of BMs, followed by various models for utilizing them in biomedical applications. The key research areas required to augment the characteristics of bacterial membranes to facilitate wider applicability are also touched upon. Overall, this review provides an interdisciplinary approach to exploit the potential of BMs and current emerging technologies to generate novel solutions to unmet clinical needs.
A Synergistic pH-Responsive Serum Albumin-Based Drug Delivery System Loaded with Doxorubicin and Pentacyclic Triterpene Betulinic Acid for Potential Treatment of NSCLC
Authors: Torres-Martinez Zally , Pérez Daraishka , Torres Grace , Estrada Sthephanie , Correa Clarissa , Mederos Natasha , Velazquez Kimberly , Castillo Betzaida , Griebenow Kai , Delgado Yamixa
Published: January 2023

Nanosized drug delivery systems (DDS) have been studied as a novel strategy against cancer due to their potential to simultaneously decrease drug inactivation and systemic toxicity and increase passive and/or active drug accumulation within the tumor(s). Triterpenes are plant-derived compounds with interesting therapeutic properties. Betulinic acid (BeA) is a pentacyclic triterpene that has great cytotoxic activity against different cancer types. Herein, we developed a nanosized protein-based DDS of bovine serum albumin (BSA) as the drug carrier combining two compounds, doxorubicin (Dox) and the triterpene BeA, using an oil-water-like micro-emulsion method. We used spectrophotometric assays to determine protein and drug concentrations in the DDS. The biophysical properties of these DDS were characterized using dynamic light scattering (DLS) and circular dichroism (CD) spectroscopy, confirming nanoparticle (NP) formation and drug loading into the protein structure, respectively. The encapsulation efficiency was 77% for Dox and 18% for BeA. More than 50% of both drugs were released within 24 h at pH 6.8, while less drug was released at pH 7.4 in this period. Co-incubation viability assays of Dox and BeA alone for 24 h demonstrated synergistic cytotoxic activity in the low μM range against non-small-cell lung carcinoma (NSCLC) A549 cells. Viability assays of the BSA-(Dox+BeA) DDS demonstrated a higher synergistic cytotoxic activity than the two drugs with no carrier. Moreover, confocal microscopy analysis confirmed the cellular internalization of the DDS and the accumulation of the Dox in the nucleus. We determined the mechanism of action of the BSA-(Dox+BeA) DDS, confirming S-phase cell cycle arrest, DNA damage, caspase cascade activation, and downregulation of epidermal growth factor receptor (EGFR) expression. This DDS has the potential to synergistically maximize the therapeutic effect of Dox and diminish chemoresistance induced by EGFR expression using a natural triterpene against NSCLC.
Theories about Developmental Dyslexia
Authors: Stein John
Published: January 2023

Despite proving its usefulness for over a century, the concept of developmental dyslexia (DD) is currently in severe disarray because of the recent introduction of the phonological theory of its causation. Since mastering the phonological principle is essential for all reading, failure to do so cannot be used to distinguish DD from the many other causes of such failure. To overcome this problem, many new psychological, signal detection, and neurological theories have been introduced recently. All these new theories converge on the idea that DD is fundamentally caused by impaired signalling of the timing of the visual and auditory cues that are essential for reading. These are provided by large ‘magnocellular’ neurones which respond rapidly to sensory transients. The evidence for this conclusion is overwhelming. Especially convincing are intervention studies that have shown that improving magnocellular function improves dyslexic children’s reading, together with cohort studies that have demonstrated that the magnocellular timing deficit is present in infants who later become dyslexic, long before they begin learning to read. The converse of the magnocellular deficit in dyslexics may be that they gain parvocellular abundance. This may often impart the exceptional ‘holistic’ talents that have been ascribed to them and that society needs to nurture.
Design and Validation of a Test to Evaluate the Execution Time and Decision-Making in Technical–Tactical Football Actions (Passing and Driving)
Authors: Calle-Jaramillo Guillermo Andres , Gonzalez-Palacio Enoc Valentin , Perez-Mendez Lewis Adrian , Rojas-Jaramillo Andres , Gonzalez-Jurado Jose Antonio
Published: January 2023

Reaction time and decision-making (DMA) in football have usually been evaluated using edited images or videos of game situations. The purpose of this research is to design and validate a test that simultaneously evaluates execution time (ET) and decision-making (DMA) in the subcategories of type of action (TA) and direction of movement (DM). Methodology: A quantitative, cross-sectional, and descriptive study of 30 young players. A total of 32 stimuli were programmed, corresponding to 64 responses, from which the total index (TI) was obtained from the division between DMA and ET. Results: The content validity index (CVI = 0.78) showed a high degree of consensus among experts. In the validation process, the intraclass correlation coefficient (ICC) was used to assess intraclass and interobserver reliability, and a moderate level of agreement was found between subjects for the TA (ICC = 0.593) and ET (ICC = 0.602) and a moderate high level of concordance for DM (ICC = 0.804) and TI (ICC = 0.855). Regarding interobserver reliability, an excellent level of agreement was found for all variables: TA (ICC = 0.998), DM (ICC = 0.998), ET (ICC = 1.000), and TI (ICC = 1.000). For the relationship between intraobserver and interobserver variables, statistical significance was established as p < 0.01. Finally, the intraobserver ETM (5.40%) and interobserver ETM (0.42%) was low compared with the reference value (5.9%). Conclusion: The designed test meets the validity criteria since the variables show sufficient intraclass reliability (test–retest) and reliability among observers.
Determining Critical Cause Combination of Fatality Accidents on Construction Sites with Machine Learning Techniques
Authors: Shuang Qing , Zhang Zerong
Published: January 2023

The construction industry is fraught with danger. The investigation of the causes of occupational accidents receives considerable attention. The purpose of this research is to determine the hierarchical relationship and critical combination of the fatal causes of accidents on construction sites. The framework for fatal cause attribute was established. Machine learning technologies were developed to predict the different types of accidents. Using feature importance, the hierarchical relationship of fatal causes was extracted. An iterative analysis algorithm was created to quantify the cause combinations. The F1 prediction score was 92.93%. The results revealed that combinations existed in fatal causes analysis, even if they were hierarchical. Furthermore, this study made recommendations for improving safety management and preventing occupational accidents. The findings of this study guide construction participants in providing early warning signs of fatal and unsafe factors, ultimately assisting in the prevention of fatalities.
Sliding Mode Control for Semi-Active Damping of Vibrations Using on/off Viscous Structural Nodes
Authors: Ostrowski Mariusz , Jedlińska Aleksandra , Popławski Błażej , Blachowski Bartlomiej , Mikułowski Grzegorz , Pisarski Dominik , Jankowski Łukasz
Published: January 2023

Structural vibrations have adverse effects and can lead to catastrophic failures. Among various methods for mitigation of vibrations, the semi-active control approaches have the advantage of not requiring a large external power supply. In this paper, we propose and test a sliding mode control method for the semi-active mitigation of vibrations in frame structures. The control forces are generated in a purely dissipative manner by means of on/off type actuators that take the form of controllable structural nodes. These nodes are essentially lockable hinges, modeled as viscous dampers, which are capable of the on/off control of the transmission of bending moments between the adjacent beams. The control aim is formulated in terms of the displacement of a selected degree of freedom. A numerically effective model of such a node is developed, and the proposed control method is verified in a numerical experiment of a four-story shear structure subjected to repeated random seismic excitations. In terms of the root-mean-square displacement, the control reduced the response by 48.4–78.4% on average, depending on the number and placement of the applied actuators. The peak mean amplitude at the first mode of natural vibrations was reduced by as much as 70.6–96.5%. Such efficiency levels confirm that the proposed control method can effectively mitigate vibrations in frame structures.
Potent Inhibition of Macropinocytosis by Niclosamide in Cancer Cells: A Novel Mechanism for the Anticancer Efficacy for the Antihelminthic
Authors: Sennoune Souad R. , Nandagopal Gunadharini Dharmalingam , Ramachandran Sabarish , Mathew Marilyn , Sivaprakasam Sathish , Jaramillo-Martinez Valeria , Bhutia Yangzom D. , Ganapathy Vadivel
Published: January 2023

Niclosamide, a drug used to treat tapeworm infection, possesses anticancer effects by interfering with multiple signaling pathways. Niclosamide also causes intracellular acidification. We have recently discovered that the amino acid transporter SLC38A5, an amino acid-dependent Na+/H+ exchanger, activates macropinocytosis in cancer cells via amino acid-induced intracellular alkalinization. Therefore, we asked whether niclosamide will block basal and SLC38A5-mediated macropinocytosis via intracellular acidification. We monitored macropinocytosis in pancreatic and breast cancer cells using TMR-dextran and the function of SLC38A5 by measuring Li+-stimulated serine uptake. The peptide transporter activity was measured by the uptake of glycylsarcosine. Treatment of the cancer cells with niclosamide caused intracellular acidification. The drug blocked basal and serine-induced macropinocytosis with differential potency, with an EC50 of ~5 μM for the former and ~0.4 μM for the latter. The increased potency for amino acid-mediated macropinocytosis is due to direct inhibition of SLC38A5 by niclosamide in addition to the ability of the drug to cause intracellular acidification. The drug also inhibited the activity of the H+-coupled peptide transporter. We conclude that niclosamide induces nutrient starvation in cancer cells by blocking macropinocytosis, SLC38A5 and the peptide transporter. These studies uncover novel, hitherto unknown, mechanisms for the anticancer efficacy of this antihelminthic.
Plasma nanoDSF Denaturation Profile at Baseline Is Predictive of Glioblastoma EGFR Status
Authors: Eyraud Rémi , Ayache Stéphane , Tsvetkov Philipp O. , Kalidindi Shanmugha Sri , Baksheeva Viktoriia E. , Boissonneau Sébastien , Jiguet-Jiglaire Carine , Appay Romain , Nanni-Metellus Isabelle , Chinot Olivier , Devred François , Tabouret Emeline
Published: January 2023

Glioblastoma (GBM) is the most frequent and aggressive primary brain tumor in adults. Recently, we demonstrated that plasma denaturation profiles of glioblastoma patients obtained using Differential Scanning Fluorimetry can be automatically distinguished from healthy controls with the help of Artificial Intelligence (AI). Here, we used a set of machine-learning algorithms to automatically classify plasma denaturation profiles of glioblastoma patients according to their EGFR status. We found that Adaboost AI is able to discriminate EGFR alterations in GBM with an 81.5% accuracy. Our study shows that the use of these plasma denaturation profiles could answer the unmet neuro-oncology need for diagnostic predictive biomarker in combination with brain MRI and clinical data, in order to allow for a rapid orientation of patients for a definitive pathological diagnosis and then treatment. We complete this study by showing that discriminating another mutation, MGMT, seems harder, and that post-surgery monitoring using our approach is not conclusive in the 48 h that follow the surgery.
HER2 and BARD1 Polymorphisms in Early HER2-Positive Breast Cancer Patients: Relationship with Response to Neoadjuvant Anti-HER2 Treatment
Authors: Novillo Apolonia , Gaibar María , Romero-Lorca Alicia , Malón Diego , Antón Beatriz , Moreno Amalia , Fernández-Santander Ana
Published: January 2023

The addition to chemotherapy of anti-HER2 drugs such as trastuzumab or pertuzumab has improved outcomes in HER2-positive breast cancer patients. However, resistance to these drugs in some patients remains a major concern. This study examines the possible association between the response to neoadjuvant anti-HER2 treatment in breast cancer patients and the presence of 28 SNPs in 17 genes involved in different cell processes (PON1, CAT, GSTP1, FCGR3, ATM, PIK3CA, HER3, BARD1, LDB2, BRINP1, chr6 intergenic region, RAB22A, TRPC6, LINC01060, EGFR, ABCB1, and HER2). Tumor samples from 50 women with early breast cancer were genotyped using the iPlex®Gold chemistry and MassARRAY platform, and patients were classified as good responders (Miller–Payne tumor grades 4–5) and poor responders (Miller–Payne tumor grades 1–3), as assessed upon surgery after 6 months of treatment. Proportions of patients with the HER2Ala1170Pro (rs1058808) SNP double mutation were higher in good (58.62%) than poor (20%) responders (p = 0.025). Similarly, proportions of patients carrying the synonymous SNP rs2070096 (BARD1Thr351=) (wv + vv) were higher in patients showing a pathological complete response (46.67%) than in those not showing this response (15.15%) (p = 0.031). The SNPs rs1058808 (HER2Ala1170Pro) and rs2070096 (BARD1Thr351=) were identified here as potential biomarkers of a good response to anti-HER2 treatment.
Combination, Modulation and Interplay of Modern Radiotherapy with the Tumor Microenvironment and Targeted Therapies in Pancreatic Cancer: Which Candidates to Boost Radiotherapy?
Authors: Benkhaled Sofian , Peters Cedric , Jullian Nicolas , Arsenijevic Tatjana , Navez Julie , Van Gestel Dirk , Moretti Luigi , Van Laethem Jean-Luc , Bouchart Christelle
Published: January 2023

Pancreatic ductal adenocarcinoma cancer (PDAC) is a highly diverse disease with low tumor immunogenicity. PDAC is also one of the deadliest solid tumor and will remain a common cause of cancer death in the future. Treatment options are limited, and tumors frequently develop resistance to current treatment modalities. Since PDAC patients do not respond well to immune checkpoint inhibitors (ICIs), novel methods for overcoming resistance are being explored. Compared to other solid tumors, the PDAC’s tumor microenvironment (TME) is unique and complex and prevents systemic agents from effectively penetrating and killing tumor cells. Radiotherapy (RT) has the potential to modulate the TME (e.g., by exposing tumor-specific antigens, recruiting, and infiltrating immune cells) and, therefore, enhance the effectiveness of targeted systemic therapies. Interestingly, combining ICI with RT and/or chemotherapy has yielded promising preclinical results which were not successful when translated into clinical trials. In this context, current standards of care need to be challenged and transformed with modern treatment techniques and novel therapeutic combinations. One way to reconcile these findings is to abandon the concept that the TME is a well-compartmented population with spatial, temporal, physical, and chemical elements acting independently. This review will focus on the most interesting advancements of RT and describe the main components of the TME and their known modulation after RT in PDAC. Furthermore, we will provide a summary of current clinical data for combinations of RT/targeted therapy (tRT) and give an overview of the most promising future directions.