bluuebunny/crossref_metadata_2025 huggingface dataset:
Sustainable Development Goals and End-of-Life Electric Vehicle Battery: Literature Review
Authors: Akram Muhammad Nadeem , Abdul-Kader Walid
Published: July 2023

With a global urgency to decrease greenhouse gas emissions, there has been an increasing demand for electric vehicles on the roads to replace vehicles that use internal combustion. Subsequently, the demand and consumption of raw materials have increased, and thus, there has been an increasing number of retired lithium-ion batteries (LIBs) that contain valuable elements. This literature review paper looks at the following: lifecycle assessments (LCA) of EV batteries, the recycling of LIBs while analyzing what studies have been conducted to improve recycling processes, what recycling facilities have been established or are being planned, studies on the circular economy, the environmental benefits of recycling end-of-life (EOL) batteries, and how LIB recycling is aligned with the Sustainable Devel opment Goals, focusing in particular on Goal 13: Climate Action.
E7 Peptide Enables BMSC Adhesion and Promotes Chondrogenic Differentiation of BMSCs Via the LncRNA H19/miR675 Axis
Authors: Shi Weili , Wu Jiangyi , Pi Yanbin , Yan Xingran , Hu Xiaoqing , Cheng Jin , Yu Huilei , Shao Zhenxing
Published: July 2023

Therapeutic strategies based on utilizing endogenous BMSCs have been developed for the regeneration of bone, cartilage, and ligaments. We previously found that E7 peptide (EPLQLKM) could enhance BMSC homing in bio-scaffolds and, therefore, promote cartilage regeneration. However, the profile and mechanisms of E7 peptide in cartilage regeneration remain elusive. In this study, we examined the effect of E7 peptide on the BMSC phenotype, including adhesion, viability and chondrogenic differentiation, and its underlying mechanism. The konjac glucomannan microsphere (KGM), a carrier material that is free of BMSC adhesion ability, was used as the solid base of E7 peptide to better explore the independent role of E7 peptide in BMSC behavior. The results showed that E7 peptide could support BMSC adhesion and viability in a comparable manner to RGD and promote superior chondrogenic differentiation to RGD. We examined differentially expressed genes of BMSCs induced by E7 compared to RGD. Subsequently, a real-time PCR validated the significantly upregulated expression of lncRNA H19, and the knockdown of lncRNA H19 or miR675, a downstream functional unit of H19, could significantly obscure the chondrogenic differentiation induced by E7. In conclusion, this study confirmed the independent role of E7 in the adhesion and viability of BMSCs and revealed the pro-chondrogenic effect of E7 on BMSCs via the H19/miR675 axis. These results could help establish new therapeutic strategies based on employing endogenous BMSCs for cartilage tissue regeneration.
Three-Dimensional Bioprinting of Ovine Aortic Valve Endothelial and Interstitial Cells for the Development of Multicellular Tissue Engineered Tissue Constructs
Authors: Immohr Moritz Benjamin , Teichert Helena Lauren , dos Santos Adrego Fabió , Schmidt Vera , Sugimura Yukiharu , Bauer Sebastian Johannes , Barth Mareike , Lichtenberg Artur , Akhyari Payam
Published: July 2023

To investigate the pathogenic mechanisms of calcified aortic valve disease (CAVD), it is necessary to develop a new three-dimensional model that contains valvular interstitial cells (VIC) and valvular endothelial cells (VEC). For this purpose, ovine aortic valves were processed to isolate VIC and VEC that were dissolved in an alginate/gelatin hydrogel. A 3D-bioprinter (3D-Bioplotter® Developer Series, EnvisionTec, Gladbeck, Germany) was used to print cell-laden tissue constructs containing VIC and VEC which were cultured for up to 21 days. The 3D-architecture, the composition of the culture medium, and the hydrogels were modified, and cell viability was assessed. The composition of the culture medium directly affected the cell viability of the multicellular tissue constructs. Co-culture of VIC and VEC with a mixture of 70% valvular interstitial cell and 30% valvular endothelial cell medium components reached the cell viability best tested with about 60% more living cells compared to pure valvular interstitial cell medium (p = 0.02). The tissue constructs retained comparable cell viability after 21 days (p = 0.90) with different 3D-architectures, including a “sandwich” and a “tube” design. Good long-term cell viability was confirmed even for thick multilayer multicellular tissue constructs. The 3D-bioprinting of multicellular tissue constructs with VEC and VIC is a successful new technique to design tissue constructs that mimic the structure of the native aortic valve for research applications of aortic valve pathologies.
Emerging Field-Effect Transistor Biosensors for Life Science Applications
Authors: Panahi Abbas , Ghafar-Zadeh Ebrahim
Published: July 2023

Field-effect transistors (FETs) have gained significant interest and hold great potential as groundbreaking sensing technology in the fields of biosensing and life science research [...]
A New Principle toward Robust Matching in Human-like Stereovision
Authors: Xie Ming , Lai Tingfeng , Fang Yuhui
Published: July 2023

Visual signals are the upmost important source for robots, vehicles or machines to achieve human-like intelligence. Human beings heavily depend on binocular vision to understand the dynamically changing world. Similarly, intelligent robots or machines must also have the innate capabilities of perceiving knowledge from visual signals. Until today, one of the biggest challenges faced by intelligent robots or machines is the matching in stereovision. In this paper, we present the details of a new principle toward achieving a robust matching solution which leverages on the use and integration of top-down image sampling strategy, hybrid feature extraction, and Restricted Coulomb Energy (RCE) neural network for incremental learning (i.e., cognition) as well as robust match-maker (i.e., recognition). A preliminary version of the proposed solution has been implemented and tested with data from Maritime RobotX Challenge. The contribution of this paper is to attract more research interest and effort toward this new direction which may eventually lead to the development of robust solutions expected by future stereovision systems in intelligent robots, vehicles, and machines.
Multivariate Optimization of Electrochemical Biosensors for the Determination of Compounds Related to Food Safety—A Review
Authors: Fernández Héctor , Zon María Alicia , Maccio Sabrina Antonella , Alaníz Rubén Darío , Di Tocco Aylen , Carrillo Palomino Roodney Alberto , Cabas Rodríguez Jose Alberto , Granero Adrian Marcelo , Arévalo Fernando J. , Robledo Sebastian Noel , Pierini Gastón Darío
Published: July 2023

We summarize the application of multivariate optimization for the construction of electrochemical biosensors. The introduction provides an overview of electrochemical biosensing, which is classified into catalytic-based and affinity-based biosensors, and discusses the most recent published works in each category. We then explore the relevance of electrochemical biosensors for food safety analysis, taking into account analytes of different natures. Then, we describe the chemometrics tools used in the construction of electrochemical sensors/biosensors and provide examples from the literature. Finally, we carefully discuss the construction of electrochemical biosensors based on design of experiments, including the advantages, disadvantages, and future perspectives of using multivariate optimization in this field. The discussion section offers a comprehensive analysis of these topics.
A Brief Review of In Situ and Operando Electrochemical Analysis of Bacteria by Scanning Probes
Authors: Lin Tzu-En , Darvishi Sorour
Published: July 2023

Bacteria are similar to social organisms that engage in critical interactions with one another, forming spatially structured communities. Despite extensive research on the composition, structure, and communication of bacteria, the mechanisms behind their interactions and biofilm formation are not yet fully understood. To address this issue, scanning probe techniques such as atomic force microscopy (AFM), scanning electrochemical microscopy (SECM), scanning electrochemical cell microscopy (SECCM), and scanning ion-conductance microscopy (SICM) have been utilized to analyze bacteria. This review article focuses on summarizing the use of electrochemical scanning probes for investigating bacteria, including analysis of electroactive metabolites, enzymes, oxygen consumption, ion concentrations, pH values, biofilms, and quorum sensing molecules to provide a better understanding of bacterial interactions and communication. SECM has been combined with other techniques, such as AFM, inverted optical microscopy, SICM, and fluorescence microscopy. This allows a comprehensive study of the surfaces of bacteria while also providing more information on their metabolic activity. In general, the use of scanning probes for the detection of bacteria has shown great promise and has the potential to provide a powerful tool for the study of bacterial physiology and the detection of bacterial infections.
Magnetically Assisted Immobilization-Free Detection of microRNAs Based on the Signal Amplification of Duplex-Specific Nuclease
Authors: Liu Gang , La Ming , Wang Jiwei , Liu Jiawen , Han Yongjun , Liu Lin
Published: July 2023

The double specific nuclease (DSN)-based methods for microRNAs (miRNAs) detection usually require the immobilization of DNA probes on a solid surface. However, such strategies have the drawbacks of low hybridization and cleavage efficiency caused by steric hindrance effect and high salt concentration on the solid surface. Herein, we proposed an immobilization-free method for miRNA detection on the basic of DSN-assisted signal amplification. The biotin- and fluorophore-labeled probes were captured by streptavidin-modified magnetic beads through streptavidin–biotin interactions, thus producing a poor fluorescence signal. Once the DNA probes were hybridized with target miRNA in solution to form DNA-miRNA duplexes, DNA stands in the duplexes would be selectively digested by DSN. The released target miRNA could initiate the next hybridization/cleavage recycling in the homogeneous solution, finally resulting in the release of numerous fluorophore-labeled fragments. The released fluorophores remained in solution and emitted strong fluorescence after treatment by the streptavidin-modified magnetic beads. The immobilization-free method achieved the assays of miRNA-21 with a detection limit down to 0.01 pM. It was employed to evaluate the expression levels of miRNA-21 in different cancer cells with satisfactory results.
Scope of Onsite, Portable Prevention Diagnostic Strategies for Alternaria Infections in Medicinal Plants
Authors: Shukla Sadhana , Singh Pushplata , Shukla Shruti , Ali Sajad , Didwania Nidhi
Published: July 2023

Medicinal plants are constantly challenged by different biotic inconveniences, which not only cause yield and economic losses but also affect the quality of products derived from them. Among them, Alternaria pathogens are one of the harmful fungal pathogens in medicinal plants across the globe. Therefore, a fast and accurate detection method in the early stage is needed to avoid significant economic losses. Although traditional methods are available to detect Alternaria, they are more time-consuming and costly and need good expertise. Nevertheless, numerous biochemical- and molecular-based techniques are available for the detection of plant diseases, but their efficacy is constrained by differences in their accuracy, specificity, sensitivity, dependability, and speed in addition to being unsuitable for direct on-field studies. Considering the effect of Alternaria on medicinal plants, the development of novel and early detection measures is required to detect causal Alternaria species accurately, sensitively, and rapidly that can be further applied in fields to speed up the advancement process in detection strategies. In this regard, nanotechnology can be employed to develop portable biosensors suitable for early and correct pathogenic disease detection on the field. It also provides an efficient future scope to convert innovative nanoparticle-derived fabricated biomolecules and biosensor approaches in the diagnostics of disease-causing pathogens in important medicinal plants. In this review, we summarize the traditional methods, including immunological and molecular methods, utilized in plant-disease diagnostics. We also brief advanced automobile and efficient sensing technologies for diagnostics. Here we are proposing an idea with a focus on the development of electrochemical and/or colorimetric properties–based nano-biosensors that could be useful in the early detection of Alternaria and other plant pathogens in important medicinal plants. In addition, we discuss challenges faced during the fabrication of biosensors and new capabilities of the technology that provide information regarding disease management strategies.
Standardizing an Experimental Murine Model of Extraparenchymal Neurocysticercosis That Immunologically Resembles Human Infection
Authors: Espinosa-Cerón Alejandro , Méndez Alejandro , Hernández-Aceves Juan , Juárez-González Juan C. , Villalobos Nelly , Hernández Marisela , Díaz Georgina , Soto Paola , Concha Luis , Pérez-Osorio Iván N. , Ortiz-Retana Juan J. , Bobes Raúl J. , Parkhouse Robert M. , Hamamoto Filho P. T. , Fragoso Gladis , Sciutto Edda
Published: July 2023

Background: Neurocysticercosis (NCC) is endemic in non-developed regions of the world. Two forms of NCC have been described, for which neurological morbidity depends on the location of the lesion, which can be either within the cerebral parenchyma or in extraparenchymal spaces. The extraparenchymal form (EXP-NCC) is considered the most severe form of NCC. EXP-NCC often requires several cycles of cysticidal treatment and the concomitant use of glucocorticoids to prevent increased inflammation, which could lead to intracranial hypertension and, in rare cases, to death. Thus, the improvement of EXP-NCC treatment is greatly needed. Methods: An experimental murine model of EXP-NCC, as an adequate model to evaluate new therapeutic approaches, and the parameters that support it are described. EXP-NCC was established by injecting 30 Taenia crassiceps cysticerci, which are less than 0.5 mm in diameter, into the cisterna magna of male and female Wistar rats. Results: Cyst implantation and infection progression were monitored by detecting the HP10 antigen and anti-cysticercal antibodies in the serum and cerebral spinal fluid (CSF) of infected rats and by magnetic resonance imaging. Higher HP10 levels were observed in CSF than in the sera, as in the case of human EXP-NCC. Low cell recruitment levels were observed surrounding established cysticerci in histological analysis, with a modest increase in GFAP and Iba1 expression in the parenchyma of female animals. Low cellularity in CSF and low levels of C-reactive protein are consistent with a weak inflammatory response to this infection. After 150 days of infection, EXP-NCC is accompanied by reduced levels of mononuclear cell proliferation, resembling the human disease. EXP-NCC does not affect the behavior or general status of the rats. Conclusions: This model will allow the evaluation of new approaches to control neuroinflammation and immunomodulatory treatments to restore and improve the specific anti-cysticercal immunity in EXP-NCC.
The Role of Staging Laparoscopy for Gastric Cancer Patients: Current Evidence and Future Perspectives
Authors: Schena Carlo Alberto , Laterza Vito , De Sio Davide , Quero Giuseppe , Fiorillo Claudio , Gunawardena Gayani , Strippoli Antonia , Tondolo Vincenzo , de’Angelis Nicola , Alfieri Sergio , Rosa Fausto
Published: July 2023

A significant proportion of patients diagnosed with gastric cancer is discovered with peritoneal metastases at laparotomy. Despite the continuous improvement in the performance of radiological imaging, the preoperative recognition of such an advanced disease is still challenging during the diagnostic work-up, since the sensitivity of CT scans to peritoneal carcinomatosis is not always adequate. Staging laparoscopy offers the chance to significantly increase the rate of promptly diagnosed peritoneal metastases, thus reducing the number of unnecessary laparotomies and modifying the initial treatment strategy of gastric cancer. The aim of this review was to provide a comprehensive summary of the current literature regarding the role of staging laparoscopy in the management of gastric cancer. Indications, techniques, accuracy, advantages, and limitations of staging laparoscopy and peritoneal cytology were discussed. Furthermore, a focus on current evidence regarding the application of artificial intelligence and image-guided surgery in staging laparoscopy was included in order to provide a picture of the future perspectives of this technique and its integration with modern tools in the preoperative management of gastric cancer.
The Talented LncRNAs: Meshing into Transcriptional Regulatory Networks in Cancer
Authors: Segal Dana , Dostie Josée
Published: July 2023

As a group of diseases characterized by uncontrollable cell growth, cancer is highly multifaceted in how it overrides checkpoints controlling proliferation. Amongst the regulators of these checkpoints, long non-coding RNAs (lncRNAs) can have key roles in why natural biological processes go haywire. LncRNAs represent a large class of regulatory transcripts that can localize anywhere in cells. They were found to affect gene expression on many levels from transcription to mRNA translation and even protein stability. LncRNA participation in such control mechanisms can depend on cell context, with given transcripts sometimes acting as oncogenes or tumor suppressors. Importantly, the tissue-specificity and low expression levels of lncRNAs make them attractive therapeutic targets or biomarkers. Here, we review the various cellular processes affected by lncRNAs and outline molecular strategies they use to control gene expression, particularly in cancer and in relation to transcription factors.
Unraveling the Significance of EPH/Ephrin Signaling in Liver Cancer: Insights into Tumor Progression and Therapeutic Implications
Authors: Papadakos Stavros P. , Stergiou Ioanna E. , Gkolemi Nikolina , Arvanitakis Konstantinos , Theocharis Stamatios
Published: July 2023

Liver cancer is a complex and challenging disease with limited treatment options and dismal prognosis. Understanding the underlying molecular mechanisms driving liver cancer progression and metastasis is crucial for developing effective therapeutic strategies. The EPH/ephrin system, which comprises a family of cell surface receptors and their corresponding ligands, has been implicated in the pathogenesis of HCC. This review paper aims to provide an overview of the current understanding of the role of the EPH/ephrin system in HCC. Specifically, we discuss the dysregulation of EPH/ephrin signaling in HCC and its impact on various cellular processes, including cell proliferation, migration, and invasion. Overall, the EPH/ephrin signaling system emerges as a compelling and multifaceted player in liver cancer biology. Elucidating its precise mechanisms and understanding its implications in disease progression and therapeutic responses may pave the way for novel targeted therapies and personalized treatment approaches for liver cancer patients. Further research is warranted to unravel the full potential of the EPH/ephrin system in liver cancer and its clinical translation.
Systematic Assessment of Small RNA Profiling in Human Extracellular Vesicles
Authors: Wang Jing , Chen Hua-Chang , Sheng Quanhu , Dawson T. Renee , Coffey Robert J. , Patton James G. , Weaver Alissa M. , Shyr Yu , Liu Qi
Published: July 2023

Motivation: Extracellular vesicles (EVs) are produced and released by most cells and are now recognized to play a role in intercellular communication through the delivery of molecular cargo, including proteins, lipids, and RNA. Small RNA sequencing (small RNA-seq) has been widely used to characterize the small RNA content in EVs. However, there is a lack of a systematic assessment of the quality, technical biases, RNA composition, and RNA biotypes enrichment for small RNA profiling of EVs across cell types, biofluids, and conditions. Methods: We collected and reanalyzed small RNA-seq datasets for 2756 samples from 83 studies involving 55 with EVs only and 28 with both EVs and matched donor cells. We assessed their quality by the total number of reads after adapter trimming, the overall alignment rate to the host and non-host genomes, and the proportional abundance of total small RNA and specific biotypes, such as miRNA, tRNA, rRNA, and Y RNA. Results: We found that EV extraction methods varied in their reproducibility in isolating small RNAs, with effects on small RNA composition. Comparing proportional abundances of RNA biotypes between EVs and matched donor cells, we discovered that rRNA and tRNA fragments were relatively enriched, but miRNAs and snoRNA were depleted in EVs. Except for the export of eight miRNAs being context-independent, the selective release of most miRNAs into EVs was study-specific. Conclusion: This work guides quality control and the selection of EV isolation methods and enhances the interpretation of small RNA contents and preferential loading in EVs.
Medical Needs and Therapeutic Options for Melanoma Patients Resistant to Anti-PD-1-Directed Immune Checkpoint Inhibition
Authors: Hassel Jessica C. , Zimmer Lisa , Sickmann Thomas , Eigentler Thomas K. , Meier Friedegund , Mohr Peter , Pukrop Tobias , Roesch Alexander , Vordermark Dirk , Wendl Christina , Gutzmer Ralf
Published: July 2023

Available 4- and 5-year updates for progression-free and for overall survival demonstrate a lasting clinical benefit for melanoma patients receiving anti-PD-directed immune checkpoint inhibitor therapy. However, at least one-half of the patients either do not respond to therapy or relapse early or late following the initial response to therapy. Little is known about the reasons for primary and/or secondary resistance to immunotherapy and the patterns of relapse. This review, prepared by an interdisciplinary expert panel, describes the assessment of the response and classification of resistance to PD-1 therapy, briefly summarizes the potential mechanisms of resistance, and analyzes the medical needs of and therapeutic options for melanoma patients resistant to immune checkpoint inhibitors. We appraised clinical data from trials in the metastatic, adjuvant and neo-adjuvant settings to tabulate frequencies of resistance. For these three settings, the role of predictive biomarkers for resistance is critically discussed, as well as are multimodal therapeutic options or novel immunotherapeutic approaches which may help patients overcome resistance to immune checkpoint therapy. The lack of suitable biomarkers and the currently modest outcomes of novel therapeutic regimens for overcoming resistance, most of them with a PD-1 backbone, support our recommendation to include as many patients as possible in novel or ongoing clinical trials.
Analysis of Expression of Programmed Cell Death Ligand 1 (PD-L1) and BRAFV600E Mutation in Thyroid Cancer
Authors: Sekino Mizuki , Iwadate Manabu , Yamaya Yukie , Matsumoto Yoshiko , Suzuki Satoshi , Mizunuma Hiroshi , Nakano Keiichi , Nakamura Izumi , Suzuki Shinichi
Published: July 2023

In thyroid cancer, it has been suggested that PD-L1 overexpression is associated with some clinicopathological factors and prognosis. The aim of this study is to characterize the expression of PD-L1, the presence of the BRAFV600E mutation, as well as cellular and humoral immunity in thyroid cancer, and to investigate the factors that predict the effectiveness of anti-PD-L1 antibody therapy. Blood samples were collected from 33 patients who were newly diagnosed with thyroid cancer after surgery or biopsy. PD-L1 expression, BRAFV600E mutation, and CD8+ expression were examined by immunohistological staining using clinical thyroid cancer specimens. With a PD-L1 staining cut-off value of 1%, 13 (39.4%) patients were classified as PD-L1 positive. Stimulation Index (SI) is an indicator of T cell activation. PD-L1 expression was significantly correlated with low SI level (p = 0.046). Moreover, BRAFV600E mutation was detected in 24 of the 33 (72.7%) patients, and was significantly associated with PD-L1 expression (p = 0.047). In addition, enhanced CD8+ expression was significantly associated with PD-L1 expression (p = 0.003). Multivariate analyses confirmed that high CRP levels (p = 0.039) were independently and significantly associated with poor progression-free survival. These findings suggest that elevated PD-L1 status can be a prognostic indicator for survival in patients with thyroid cancer when comprehensively assessed using the expression of CD8+, the presence of BRAFV600E mutation and the patient’s immune status.
Usefulness of BRCA and ctDNA as Prostate Cancer Biomarkers: A Meta-Analysis
Authors: Domrazek Kinga , Pawłowski Karol , Jurka Piotr
Published: July 2023

Prostate cancer represents the most common male urologic neoplasia. Tissue biopsies are the gold standard in oncology for diagnosing prostate cancer. We conducted a study to find the most reliable and noninvasive diagnostic tool. We performed a systematic review and meta-analysis of two biomarkers which we believe are the most interesting: BRCA (BRCA1 and 2) and ctDNA. Our systematic research yielded 248 articles. Forty-five duplicates were first excluded and, upon further examination, a further 203 articles were excluded on the basis of the inclusion and exclusion criteria, leaving 25 articles. A statistical analysis of the obtained data has been performed. With a collective calculation, BRCA1 was expressed in 2.74% of all cases from 24,212 patients examined and BRCA2 in 1.96% of cases from 20,480 patients. In a total calculation using ctDNA, it was observed that 89% of cases from 1198 patients exhibited high expression of circulating tumor DNA. To date, no ideal PCa biomarker has been found. Although BRCA1 and BRCA2 work well for breast and ovarian cancers, they do not seem to be reliable for prostate cancer. ctDNA seems to be a much better biomarker; however, there are few studies in this area. Further studies need to be performed.
Identification of a Novel SSTR3 Full Agonist for the Treatment of Nonfunctioning Pituitary Adenomas
Authors: Modena Daniela , Moras Maria Luisa , Sandrone Giovanni , Stevenazzi Andrea , Vergani Barbara , Dasgupta Pooja , Kliever Andrea , Gulde Sebastian , Marangelo Alessandro , Schillmaier Mathias , Luque Raul M. , Bäuerle Stephen , Pellegata Natalia S. , Schulz Stefan , Steinkühler Christian
Published: July 2023

Somatostatin receptor (SSTR) agonists have been extensively used for treating neuroendocrine tumors. Synthetic therapeutic agonists showing selectivity for SSTR2 (Octreotide) or for SSTR2 and SSTR5 (Pasireotide) have been approved for the treatment of patients with acromegaly and Cushing’s syndrome, as their pituitary tumors highly express SSTR2 or SSTR2/SSTR5, respectively. Nonfunctioning pituitary adenomas (NFPAs), which express high levels of SSTR3 and show only modest response to currently available SSTR agonists, are often invasive and cannot be completely resected, and therefore easily recur. The aim of the present study was the evaluation of ITF2984, a somatostatin analog and full SSTR3 agonist, as a new potential treatment for NFPAs. ITF2984 shows a 10-fold improved affinity for SSTR3 compared to Octreotide or Pasireotide. Molecular modeling and NMR studies indicated that the higher affinity for SSTR3 correlates with a higher stability of a distorted β-I turn in the cyclic peptide backbone. ITF2984 induces receptor internalization and phosphorylation, and triggers G-protein signaling at pharmacologically relevant concentrations. Furthermore, ITF2984 displays antitumor activity that is dependent on SSTR3 expression levels in the MENX (homozygous mutant) NFPA rat model, which closely recapitulates human disease. Therefore, ITF2984 may represent a novel therapeutic option for patients affected by NFPA.
PRMT-1 and p120-Catenin as EMT Mediators in Osimertinib Resistance in NSCLC
Authors: Racherla Kavya Sri , Dovalovsky Katrina , Patel Meet , Harper Emma , Barnard Jacob , Nasifuzzaman S M , Smith Mason , Sikand Riya , Drinka Eva , Puri Neelu
Published: July 2023

Osimertinib, an irreversible tyrosine kinase inhibitor, is a first-line therapy in EGFR-mutant NSCLC patients. Prolonged treatment with Osimertinib leads to resistance due to an acquired C797S mutation in the EGFR domain and other mechanisms, such as epithelial-mesenchymal transition (EMT). In this study, we investigated the role of PRMT-1 and p120-catenin in mediating Osimertinib resistance (OR) through EMT. These studies found upregulation of gene and protein expression of PRMT-1, p120-catenin and Kaiso factor. Knockdown of p120-catenin using siRNA increased OR efficacy by 45% as compared to cells treated with mock siRNA and OR. After 24 h of transfection, the percentage wound closure in cells transfected with p120-catenin siRNA was 26.2%. However, in mock siRNA-treated cells the wound closure was 7.4%, showing its involvement in EMT. We also found high levels of p120-catenin expressed in 30% of smokers as compared to 5.5% and 0% of non-smokers and quit-smokers (respectively) suggesting that smoking may influence p120-catenin expression in NSCLC patients. These results suggest that biomarkers such as PRMT-1 may mediate EMT by methylating Twist-1 and increasing p120-catenin expression, which causes transcriptional activation of genes associated with Kaiso factor to promote EMT in Osimertinib-resistant cells.
Alterations in the Epigenetic Machinery Associated with Prostate Cancer Health Disparities
Authors: Craddock Jenna , Jiang Jue , Patrick Sean M. , Mutambirwa Shingai B. A. , Stricker Phillip D. , Bornman M. S. Riana , Jaratlerdsiri Weerachai , Hayes Vanessa M.
Published: July 2023

Prostate cancer is driven by acquired genetic alterations, including those impacting the epigenetic machinery. With African ancestry as a significant risk factor for aggressive disease, we hypothesize that dysregulation among the roughly 656 epigenetic genes may contribute to prostate cancer health disparities. Investigating prostate tumor genomic data from 109 men of southern African and 56 men of European Australian ancestry, we found that African-derived tumors present with a longer tail of epigenetic driver gene candidates (72 versus 10). Biased towards African-specific drivers (63 versus 9 shared), many are novel to prostate cancer (18/63), including several putative therapeutic targets (CHD7, DPF3, POLR1B, SETD1B, UBTF, and VPS72). Through clustering of all variant types and copy number alterations, we describe two epigenetic PCa taxonomies capable of differentiating patients by ancestry and predicted clinical outcomes. We identified the top genes in African- and European-derived tumors representing a multifunctional “generic machinery”, the alteration of which may be instrumental in epigenetic dysregulation and prostate tumorigenesis. In conclusion, numerous somatic alterations in the epigenetic machinery drive prostate carcinogenesis, but African-derived tumors appear to achieve this state with greater diversity among such alterations. The greater novelty observed in African-derived tumors illustrates the significant clinical benefit to be derived from a much needed African-tailored approach to prostate cancer healthcare aimed at reducing prostate cancer health disparities.
Feature Importance Analysis of a Deep Learning Model for Predicting Late Bladder Toxicity Occurrence in Uterine Cervical Cancer Patients
Authors: Cheon Wonjoong , Han Mira , Jeong Seonghoon , Oh Eun Sang , Lee Sung Uk , Lee Se Byeong , Shin Dongho , Lim Young Kyung , Jeong Jong Hwi , Kim Haksoo , Kim Joo Young
Published: July 2023

(1) In this study, we developed a deep learning (DL) model that can be used to predict late bladder toxicity. (2) We collected data obtained from 281 uterine cervical cancer patients who underwent definitive radiation therapy. The DL model was trained using 16 features, including patient, tumor, treatment, and dose parameters, and its performance was compared with that of a multivariable logistic regression model using the following metrics: accuracy, prediction, recall, F1-score, and area under the receiver operating characteristic curve (AUROC). In addition, permutation feature importance was calculated to interpret the DL model for each feature, and the lightweight DL model was designed to focus on the top five important features. (3) The DL model outperformed the multivariable logistic regression model on our dataset. It achieved an F1-score of 0.76 and an AUROC of 0.81, while the corresponding values for the multivariable logistic regression were 0.14 and 0.43, respectively. The DL model identified the doses for the most exposed 2 cc volume of the bladder (BD2cc) as the most important feature, followed by BD5cc and the ICRU bladder point. In the case of the lightweight DL model, the F-score and AUROC were 0.90 and 0.91, respectively. (4) The DL models exhibited superior performance in predicting late bladder toxicity compared with the statistical method. Through the interpretation of the model, it further emphasized its potential for improving patient outcomes and minimizing treatment-related complications with a high level of reliability.
Regulation and Functions of α6-Integrin (CD49f) in Cancer Biology
Authors: Khademi Rahele , Malekzadeh Hossein , Bahrami Sara , Saki Najmaldin , Khademi Reyhane , Villa-Diaz Luis G.
Published: July 2023

Over the past decades, our knowledge of integrins has evolved from being understood as simple cell surface adhesion molecules to receptors that have a complex range of intracellular and extracellular functions, such as delivering chemical and mechanical signals to cells. Consequently, they actively control cellular proliferation, differentiation, and apoptosis. Dysregulation of integrin signaling is a major factor in the development and progression of many tumors. Many reviews have covered the broader integrin family in molecular and cellular studies and its roles in diseases. Nevertheless, further understanding of the mechanisms specific to an individual subunit of different heterodimers is more useful. Thus, we describe the current understanding of and exploratory investigations on the α6-integrin subunit (CD49f, VLA6; encoded by the gene itga6) in normal and cancer cells. The roles of ITGA6 in cell adhesion, stemness, metastasis, angiogenesis, and drug resistance, and as a diagnosis biomarker, are discussed. The role of ITGA6 differs based on several features, such as cell background, cancer type, and post-transcriptional alterations. In addition, exosomal ITGA6 also implies metastatic organotropism. The importance of ITGA6 in the progression of a number of cancers, including hematological malignancies, suggests its potential usage as a novel prognostic or diagnostic marker and useful therapeutic target for better clinical outcomes.
Local Treatment of Hepatocellular Carcinoma with Oligometastases: A Systematic Review and Meta-Analysis
Authors: Kim Sooyeon , Lee Jungsue , Rim Chai Hong
Published: July 2023

Although recent studies have shown favorable results after local treatment for oligometastases, the clinical decision of applying local treatment for oligometastatic hepatocellular carcinoma (HCC) remains controversial. This meta-analysis aimed to investigate the benefits of local treatment for HCC oligometastases. Pubmed, Embase, Medline, and the Cochrane library were searched for studies until 1 May 2022. Clinical studies involving at least five cases of HCC oligometsatases treated with local modalities were included. The primary endpoint was overall survival (OS). The benefit of local treatment was assessed as the pooled odds ratio (OR) among comparative series, and the pooled OS percentile was calculated from all studies including patients treated with local treatment. Complications of grade ≥ 3 were assessed subjectively. A total of 10 studies involving 527 patients were included. Radiotherapy and radiofrequency ablation (RFA) were mainly performed (six and five studies) as local modalities treating oligometastases. Pooled OR of comparative series favored the use of local treatment (4.664, 95% confidence interval [CI]: 2.595–8.380, p < 0.001, I2: ~0.0%). Including all cohorts with patients who underwent local treatment, pooled rates of 1-year OS were 71.8% (95% CI: 59.0–81.9; I2 = 81.5%), and pooled 2-year OS were 43.3% (95% CI: 29.1–59.6; I2 = 85.4%). Except for temporal or pre-existing toxicities, grade ≤ 3 complications were reported less than 10% in most studies, although common toxicities include pneumothorax and hematologic deficiency after RFA and radiotherapy, respectively. Grade 5 toxicity has not yet been reported. This systematic review supports the application of local treatment for treating HCC oligometastases.
The Hippo Pathway Effectors YAP/TAZ-TEAD Oncoproteins as Emerging Therapeutic Targets in the Tumor Microenvironment
Authors: Mokhtari Reza Bayat , Ashayeri Neda , Baghaie Leili , Sambi Manpreet , Satari Kosar , Baluch Narges , Bosykh Dmitriy A. , Szewczuk Myron R. , Chakraborty Sayan
Published: July 2023

Various cancer cell-associated intrinsic and extrinsic inputs act on YAP/TAZ proteins to mediate the hyperactivation of the TEAD transcription factor-based transcriptome. This YAP/TAZ-TEAD activity can override the growth-limiting Hippo tumor-suppressor pathway that maintains normal tissue homeostasis. Herein, we provide an integrated summary of the contrasting roles of YAP/TAZ during normal tissue homeostasis versus tumor initiation and progression. In addition to upstream factors that regulate YAP/TAZ in the TME, critical insights on the emerging functions of YAP/TAZ in immune suppression and abnormal vasculature development during tumorigenesis are illustrated. Lastly, we discuss the current methods that intervene with the YAP/TAZ-TEAD oncogenic signaling pathway and the emerging applications of combination therapies, gut microbiota, and epigenetic plasticity that could potentiate the efficacy of chemo/immunotherapy as improved cancer therapeutic strategies.
Electrochemical Sensing of Zinc Oxide and Peroxide Nanoparticles: Modification with Meso-tetrakis(4-carboxyphenyl) Porphyrin
Authors: Wang Kailai , Lai Edward P. C.
Published: July 2023

An electrochemical method was developed to investigate the redox properties of zinc oxide (ZnO), zinc peroxide (ZnO2), and sodium-doped zinc peroxide (Na-ZnO2) nanoparticles. The intention was to distinguish the identity of these nanoparticles among themselves, and from other transition metal oxide nanoparticles (TMONPs). Analysis of 3 mM sodium metabisulfite by cyclic voltammetry (CV) produced anodic/cathodic peak currents that are linearly related to the mass of deposited nanoparticles. A graphite working electrode was essential to the oxidation of metabisulfite. ZnO nanoparticles were crucial to the enhancement of metabisulfite oxidation current, and PPy coating could suppress the current enhancement by covering all nanoparticle surfaces. Furthermore, meso-tetrakis(4-carboxyphenyl) porphyrin was demonstrated to be a good chemical reagent that facilitates the differentiation of ZnO from ZnO2 and nanoparticles by CV analysis.
The Experiences of Australian School Mental Health Professionals during COVID-19 Lockdowns
Authors: Berger Emily , Mackie Grace , Reupert Andrea , Greenfeld Daliya , Allen Kelly-Ann , May Fiona , Wurf Gerald , Summers Dianne , Morris Zoe
Published: July 2023

Young people have emerged as one of the most impacted groups from the COVID-19 pandemic and related restrictions to daily activities, with disruptions to schooling, social interactions, and connections. Simultaneously, students’ access to school mental health professionals were restricted or modified. The aim of this paper was to identify how school mental health professionals supported and addressed the mental health needs of young people during COVID-19 restrictions in Australia. School mental health professionals were surveyed during the 2020 lockdowns using a questionnaire designed by researchers in the United States of America. The innovations school mental health staff adopted to support students during lockdowns and remote learning were presented, including telehealth services, digital resources, and the online training and support they received/provided. The barriers and facilitators to providing counselling and assessment services during lockdowns were identified, including issues with providing psychometric assessments during remote learning, and ethical concerns when delivering remote counselling to students. Recommendations have been included, which address how school mental health professionals could be supported to assess and treat young people during future pandemics and school restrictions.
Do Girls Have an Advantage Compared to Boys When Their Motor Skills Are Tested Using the Movement Assessment Battery for Children, 2nd Edition?
Authors: Smits-Engelsman Bouwien , Coetzee Dané , Valtr Ludvík , Verbecque Evi
Published: July 2023

This study aims to investigate sex-related differences in raw item scores on the Movement Assessment Battery for Children, 2nd Edition (MABC-2) in a large data set collected in different regions across the world, seeking to unravel whether there is an interaction effect between sex and the origin of the sample (European versus African). In this retrospective study, a secondary analysis was performed on anonymized data of 7654 children with a mean age of 8.6 (range 3 to 16; SD: 3.4), 50.0% of whom were boys. Since country-specific norms were not available for all samples, the raw scores per age band (AB) were used for analysis. Our results clearly show that in all age bands sex-related differences are present. In AB1 and AB2, girls score better on most manual dexterity and balance items, but not aiming and catching items, whereas in AB3 the differences seem to diminish. Especially in the European sample, girls outperform boys in manual dexterity and balance items, whereas in the African sample these differences are less marked. In conclusion, separate norms for boys and girls are needed in addition to separate norms for geographical regions.
Examining a Complex Model Linking Maternal Reflective Functioning, Maternal Meta-Emotion Philosophies, and Child Emotion Regulation
Authors: Shao Rong , Liu Sitong , Coplan Robert J. , Chen Xi , Liu Junsheng
Published: July 2023

Parental Reflective Functioning (PRF) refers to parents’ ability to understand their children’s behavior in light of underlying mental states such as thoughts, desires, and intentions. This study aimed to investigate whether maternal meta-emotion philosophies (i.e., emotion coaching, emotion dismissing) mediated the relation between maternal RF and child emotion regulation (ER). Additionally, children’s genders and ages were examined as moderators of the associations between maternal RF and maternal meta-emotion philosophies. The sample comprises 667 Chinese mothers of children aged 4–6 years. Mothers completed questionnaires assessing their reflective functioning, emotion coaching and dismissing, and child emotion regulation. Results indicated both a direct link between maternal RF and child emotion regulation, as well as indirect pathways mediated by emotion coaching and dismissing. A child’s gender and age also moderated the relations between maternal RF and meta-emotion philosophies. Specifically, the negative association between maternal pre-mentalizing modes and emotion coaching was stronger for mothers of girls than boys; whereas the negative association between maternal certainty of mental states and emotion dismissing, as well as the positive association between maternal interest and curiosity and emotion coaching were both stronger for mothers of younger children than older children. The findings suggest that emotion coaching and dismissing mediate the relation between maternal PRF and the emotion regulation of children.
Nanostructures and Thin Films of Poly(Ethylene Glycol)-Based Surfactants and Polystyrene Nanocolloid Particles on Mica: An Atomic Force Microscopy Study
Authors: Walker John , Schofield Andrew B. , Koutsos Vasileios
Published: July 2023

We studied the nanostructures and ultrathin films resulting from the deposition and adsorption of polystyrene nanocolloidal particles and methoxy poly(ethylene glycol) methacrylate surfactants on mica surfaces from mixed suspensions in water. The samples were prepared by droplet evaporation and dip coating and imaged with atomic force microscopy. Topography and phase imaging revealed a significant richness in morphological features of the deposited/adsorbed films. We observed uniform ultrathin films and extended islands of the surfactant oligomers indicating their self-assembly in monolayers and multilayers, while the polystyrene nanocolloids were embedded within the surfactant structures. Droplet evaporation resulted in the migration of particles towards the edges of the droplet leaving an intricate network of imprints within the surfactant film. Dip coating induced the formation of extended nanocolloid clusters with colloidal crystalline structuring.
Research Progress on the Wear and Corrosion Resistant Plasma Electrolytic Oxidation Composite Coatings on Magnesium and Its Alloys
Authors: Zhao Chen , Wang Xingwei , Yu Bo , Cai Meirong , Yu Qiangliang , Zhou Feng
Published: July 2023

Plasma electrolytic oxidation (PEO), as a cost effective and environmentally friendly technology, has been applied on magnesium and its alloys to improve wear and corrosion resistance. Additionally, combining with particles addition in the electrolyte and/or various post-treatments could diminish the intrinsic structural defects of the PEO coatings and provide multifunctionalities, including wear resistance, corrosion resistance, self-lubrication, and self-healing. This paper reviews recent progress on PEO composite coatings prepared by in situ incorporation of functional particles and/or post-treatments on magnesium and its alloys. The focus is given to the microstructural and functional changes of the PEO coatings, particularly on the wear and corrosion behaviors.
Computation of the Exact Forms of Waves for a Set of Differential Equations Associated with the SEIR Model of Epidemics
Authors: Vitanov Nikolay K. , Dimitrova Zlatinka I.
Published: July 2023

We studied obtaining exact solutions to a set of equations related to the SEIR (Susceptible-Exposed-Infectious-Recovered) model of epidemic spread. These solutions may be used to model epidemic waves. We transformed the SEIR model into a differential equation that contained an exponential nonlinearity. This equation was then approximated by a set of differential equations which contained polynomial nonlinearities. We solved several equations from the set using the Simple Equations Method (SEsM). In doing so, we obtained many new exact solutions to the corresponding equations. Several of these solutions can describe the evolution of epidemic waves that affect a small percentage of individuals in the population. Such waves have frequently been observed in the COVID-19 pandemic in recent years. The discussion shows that SEsM is an effective methodology for computing exact solutions to nonlinear differential equations. The exact solutions obtained can help us to understand the evolution of various processes in the modeled systems. In the specific case of the SEIR model, some of the exact solutions can help us to better understand the evolution of the quantities connected to the epidemic waves.