bluuebunny/crossref_metadata_2025 huggingface dataset:
Usefulness of COL11A1 as a Prognostic Marker of Tumor Infiltration
Authors: Freire Javier , García-Berbel Pilar , Caramelo Belén , García-Berbel Lucía , Ovejero Victor J. , Cadenas Nuria , Azueta Ainara , Gómez-Román Javier
Published: September 2023

Background: Determining the infiltration of carcinomas is essential for the proper follow-up and treatment of cancer patients. However, it continues to be a diagnostic challenge for pathologists in multiple types of tumors. In previous studies (carried out in surgical specimens), the protein COL11A1 has been postulated as an infiltration marker mainly expressed in the extracellular matrix (ECM). We hypothesized that a differential expression of COL11A1 may exist in the peritumoral stroma of tumors that have acquired infiltrating properties and that it may be detected in the small biopsies usually available in normal clinical practice. Material and methods: In our study, we performed immunohistochemical staining in more than 350 invasive and noninvasive small samples obtained via core needle biopsy (CNB), colonoscopy, or transurethral resection of bladder tumor (TURBT) of breast, colorectal, bladder, and ovarian cancer. Results: Our results revealed that COL11A1 immunostaining had a sensitivity to classify the samples into infiltrative vs. noninfiltrative tumors of 94% (breast), 97% (colorectal), >90% (bladder), and 74% (ovarian); and a specificity of 97% (breast), 100% (colorectal), and >90% (bladder). In ovarian cancer, the negative predictive value (0.59) did not present improvement over the usual histopathological markers. In all samples tested, the cumulative sensitivity was 86% and the specificity 96% (p < 0.0001). Conclusions: COL11A1-positive immunostaining in small biopsies of breast, colon, bladder and ovarian cancer is an accurate predictive marker of tumor infiltration that can be easily implemented in daily clinical practice.
Effect of Carbamylated Erythropoietin in a Chronic Model of TNBS-Induced Colitis
Authors: Silva Inês , Gomes Mário , Alípio Carolina , Vitoriano Jéssica , Estarreja João , Mendes Priscila , Pinto Rui , Mateus Vanessa
Published: September 2023

Background: Inflammatory bowel disease (IBD) is a public health issue with a growing prevalence, which can be divided into two phenotypes, namely Crohn’s disease (CD) and ulcerative colitis (UC). Currently, used therapy is based only on symptomatic and/or palliative pharmacological approaches. These treatments seek to induce and maintain remission of the disease and ameliorate its secondary effects; however, they do not modify or reverse the underlying pathogenic mechanism. Therefore, it is essential to investigate new potential treatments. Carbamylated erythropoietin (cEPO) results from the modification of the Erythropoietin (EPO) molecule, reducing cardiovascular-related side effects from the natural erythropoiesis stimulation. cEPO has been studied throughout several animal models, which demonstrated an anti-inflammatory effect by decreasing the production of several pro-inflammatory cytokines. Aim: This study aimed to evaluate the efficacy and safety of cEPO in a chronic TNBS-induced colitis model in rodents. Methods: Experimental colitis was induced by weekly intrarectal (IR) administrations of 1% TNBS for 5 weeks in female CD-1 mice. Then, the mice were treated with 500 IU/kg/day or 1000 IU/kg/day of cEPO through intraperitoneal injections for 14 days. Results: cEPO significantly reduced the concentration of alkaline phosphatase (ALP), fecal hemoglobin, tumor necrosis factor (TNF)-α, and interleukin (IL)-10. Also, it demonstrated a beneficial influence on the extra-intestinal manifestations, with the absence of significant side effects of its use. Conclusion: Considering the positive results from cEPO in this experiment, it may arise as a new possible pharmacological approach for the future management of IBD.
Obesity-Related Kidney Disease: Current Understanding and Future Perspectives
Authors: Kreiner Frederik F. , Schytz Philip Andreas , Heerspink Hiddo J. L. , von Scholten Bernt Johan , Idorn Thomas
Published: September 2023

Obesity is a serious chronic disease and an independent risk factor for the new onset and progression of chronic kidney disease (CKD). CKD prevalence is expected to increase, at least partly due to the continuous rise in the prevalence of obesity. The concept of obesity-related kidney disease (OKD) has been introduced to describe the still incompletely understood interplay between obesity, CKD, and other cardiometabolic conditions, including risk factors for OKD and cardiovascular disease, such as diabetes and hypertension. Current therapeutics target obesity and CKD individually. Non-pharmacological interventions play a major part, but the efficacy and clinical applicability of lifestyle changes and metabolic surgery remain debatable, because the strategies do not benefit everyone, and it remains questionable whether lifestyle changes can be sustained in the long term. Pharmacological interventions, such as sodium-glucose co-transporter 2 inhibitors and the non-steroidal mineralocorticoid receptor antagonist finerenone, provide kidney protection but have limited or no impact on body weight. Medicines based on glucagon-like peptide-1 (GLP-1) induce clinically relevant weight loss and may also offer kidney benefits. An urgent medical need remains for investigations to better understand the intertwined pathophysiologies in OKD, paving the way for the best possible therapeutic strategies in this increasingly prevalent disease complex.
Auranofin Modulates Thioredoxin Reductase/Nrf2 Signaling in Peripheral Immune Cells and the CNS in a Mouse Model of Relapsing–Remitting EAE
Authors: Al-Kharashi Layla A. , Al-Harbi Naif O. , Ahmad Sheikh F. , Attia Sabry M. , Algahtani Mohammad M. , Ibrahim Khalid E. , Bakheet Saleh A. , Alanazi Mohammed M. , Alqarni Saleh A. , Alsanea Sary , Nadeem Ahmed
Published: September 2023

Multiple sclerosis (MS) is one of the most prevalent chronic inflammatory autoimmune diseases. It causes the demyelination of neurons and the subsequent degeneration of the central nervous system (CNS). The infiltration of leukocytes of both myeloid and lymphoid origins from the systemic circulation into the CNS triggers autoimmune reactions through the release of multiple mediators. These mediators include oxidants, pro-inflammatory cytokines, and chemokines which ultimately cause the characteristic plaques observed in MS. Thioredoxin reductase (TrxR) and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling plays a crucial role in the regulation of inflammation by modulating the transcription of antioxidants and the suppression of inflammatory cytokines. The gold compound auranofin (AFN) is known to activate Nrf2 through the inhibition of TrxR; however, the effects of this compound have not been explored in a mouse model of relapsing–remitting MS (RRMS). Therefore, this study explored the influence of AFN on clinical features, TrxR/Nrf2 signaling [heme oxygenase 1 (HO-1), superoxide dismutase 1 (SOD-1)] and oxidative/inflammatory mediators [IL-6, IL-17A, inducible nitric oxide synthase (iNOS), myeloperoxidase (MPO), nitrotyrosine] in peripheral immune cells and the CNS of mice with the RR type of EAE. Our results showed an increase in TrxR activity and a decrease in Nrf2 signaling in SJL/J mice with RR-EAE. The treatment with AFN caused the amelioration of the clinical features of RR-EAE through the elevation of Nrf2 signaling and the subsequent upregulation of the levels of antioxidants as well as the downregulation of oxidative/pro-inflammatory mediators in peripheral immune cells and the CNS. These data suggest that AFN may be beneficial in the treatment of RRMS.
Ovarian Torsion in Polycystic Ovary Syndrome: A Potential Threat?
Authors: Psilopatis Iason , Damaskos Christos , Garmpis Nikolaos , Vrettou Kleio , Garmpi Anna , Antoniou Efstathios A. , Chionis Athanasios , Nikolettos Konstantinos , Kontzoglou Konstantinos , Dimitroulis Dimitrios
Published: September 2023

Polycystic ovary syndrome (PCOS) constitutes the most prevalent endocrine disorder in women of reproductive age worldwide. Given the increased risk of ovarian torsion in the presence of large ovarian cysts, polycystic ovarian syndrome could be regarded as one of the most significant risk factors for ovarian and/or adnexal torsion in cases of significantly enlarged ovaries. The aim of the present review is to investigate, for the first time, the association between polycystic ovarian syndrome and ovarian torsion. We performed a review of the literature using the MEDLINE and LIVIVO databases in order to find relevant studies. By using the search terms “polycystic ovarian syndrome” and “ovarian torsion”, we were able to identify 14 studies published between 1995 and 2019. The present work constitutes the most up-to-date, comprehensive literature review focusing on the risk of ovarian/adnexal torsion in patients with polycystic ovaries. Ovarian/adnexal torsion seems to be a feared complication in patients with polycystic ovary syndrome. Acute lower abdominal pain in patients with known polycystic ovaries represents the most common symptom, while diagnostic assessment almost always incorporates transvaginal ultrasound and computer tomography or magnetic resonance tomography scans. In case of suspected torsion, emergency laparoscopy with ovarian or adnexal detorsion seems to be the standard therapeutic approach with a view to restitute the interrupted blood supply. In cases of repeated ovarian/adnexal torsions, ovariopexy or ovariectomy/adnexectomy had to be discussed with the patient in the context of risk recurrence minimization.
Immunosenescence and Immune Exhaustion Are Associated with Levels of Protein-Bound Uremic Toxins in Patients on Hemodialysis
Authors: Tourountzis Theodoros , Lioulios Georgios , Van Laecke Steven , Ginikopoulou Evdoxia , Nikolaidou Vasiliki , Moysidou Eleni , Stai Stamatia , Christodoulou Michalis , Fylaktou Asimina , Glorieux Griet , Stangou Maria
Published: September 2023

Background: The accumulation of protein-bound uremic toxins (PBUTs) in chronic kidney disease may affect patients’ immune status. The aim of the study was to evaluate their potential impacts on lymphocyte alterations in patients on hemodialysis (HD). Methods: The plasma levels of PBUTs were assessed in 54 patients on HD and 31 healthy individuals, using ultra-performance liquid chromatography. The results correlated with the senescent and exhausted status of lymphocytes, based on certain surface molecules, analyzed by flow cytometry. Results: The plasma levels of PBUTs were significantly increased in the patients on HD compared with the healthy controls. The patients with residual kidney function had reduced hippuric acid (HA) levels, total (p = 0.03) and free (p = 0.04), and free IxS levels (p = 0.02). The total and free HA levels correlated negatively with less differentiated subpopulations, CD4+CD45RA+CD31+ (p = 0.037 and p = 0.027), CD8+CD28+CD57− (p = 0.01, p = 0.01), and naïve B cells (CD19+IgD+CD27−) (p = 0.04, p = 0.03). Both the total and the free pCS levels correlated positively with exhausted CD4 cells, p = 0.02 and p = 0.01, respectively. A multivariate analysis showed that IxS and age were the main independent parameters implicated in the reduction intotal CD4 and B lymphocytes and their naïve and early differentiated subsets. Conclusions: Increased PBUTs levels are associated with immune disturbances of patients on HD, HA, and IxS in the immunosenescent and pCS in the immunoexhaustion alterations.
Polymorphisms in the Drug Transporter Gene ABCB1 Are Associated with Drug Response in Saudi Epileptic Pediatric Patients
Authors: Magadmi Rania , Alyoubi Reem , Moshrif Tahani , Bakhshwin Duaa , Suliman Bandar A. , Kamel Fatemah , Jamal Maha , Burzangi Abdulhadi S. , Basit Sulman
Published: September 2023

Epilepsy is one of the most common chronic neurodisorders in the pediatric age group. Despite the availability of over 20 anti-seizure medications (ASMs) on the market, drug-resistant epilepsy still affects one-third of individuals. Consequently, this research aimed to investigate the association between single-nucleotide polymorphisms (SNPs) of the ATP-binding cassette subfamily B member 1 (ABCB1) gene in epileptic pediatric patients and their response to ASMs. This multicentric, cross-sectional study was conducted among Saudi children with epilepsy in Jeddah, Saudi Arabia. The polymorphism variants of ABCB1 rs1128503 at exon 12, rs2032582 at exon 21, and rs1045642 at exon 26 were genotyped using the Sanger sequencing technique. The study included 85 children with epilepsy: 43 patients demonstrated a good response to ASMs, while 42 patients exhibited a poor response. The results revealed that good responders were significantly more likely to have the TT genotypes at rs1045642 and rs2032582 SNPs compared to poor responders. Additionally, haplotype analysis showed that the T-G-C haplotype at rs1128503, rs2032582, and rs1045642 was only present in poor responders. In conclusion, this study represents the first pharmacogenetic investigation of the ABCB1 gene in Saudi epileptic pediatric patients and demonstrates a significant association between rs1045642 and rs2032582 variants and patient responsiveness. Despite the small sample size, the results underscore the importance of personalized treatment for epileptic patients.
ITCH-Mediated Ubiquitylation of ITGB3 Promotes Cell Proliferation and Invasion of Ectopic Endometrial Stromal Cells in Ovarian Endometriosis
Authors: Zhang Liansuo , Shao Wei , Li Mingqing , Liu Songping
Published: September 2023

Post-translational modification of proteins is involved in the occurrence of endometriosis (EM); however, the role of ubiquitination modification in EM remains unclear. Integrin β3 (ITGB3) is one of the β-subunits of integrins, which plays a key role in tumor progression. In this study, we investigated the roles of ITGB3 and ITCH, one of the ubiquitin E3 ligases, in ectopic endometrial stromal cells (ESCs) and EM. Primary ectopic ESCs and normal ESCs were isolated and purified. Western blot was used to detect the expression of ITGB3 and ITCH in ESCs. The interaction between ITGB3 and ITCH in ESCs was investigated by the co-immunoprecipitation and ubiquitylation analysis. With or without the overexpression of ITCH and/or ITGB3, the proliferation and invasion of ectopic ESCs were detected by the CCK8 assay and transwell migration assay, respectively. We found that ITGB3 is upregulated in ectopic ESCs from patients with EM. ITCH interacts with ITGB3 by co-immunoprecipitation, and ITCH-overexpressing significantly increased the ubiquitination of ITGB3. The data of the CCK8 assays showed that ITGB3 overexpression significantly promoted cell proliferation of ectopic ESCs at 12, 24, 48, and 72 h. The transwell migration assays showed that ITGB3 overexpression significantly enhanced the invasive ability. However, ITCH had the opposite effects in both assays. Our findings indicate that ITCH-mediated ubiquitylation of ITGB3 regulates the proliferation and invasion ability of ectopic ESCs in EM.
The Use of Small-Molecule Compounds for Cell Adhesion and Migration in Regenerative Medicine
Authors: Mitchell Juan , Lo Kevin W.-H.
Published: September 2023

Cell adhesion is essential for cell survival, communication, and regulation, and it is of fundamental importance in the development and maintenance of tissues. Cell adhesion has been widely explored due to its many important roles in the fields of tissue regenerative engineering and cell biology. This is because the mechanical interactions between a cell and its extracellular matrix (ECM) can influence and control cell behavior and function. Currently, biomaterials for regenerative medicine have been heavily investigated as substrates for promoting a cells’ adhesive properties and subsequent proliferation, tissue differentiation, and maturation. Specifically, the manipulation of biomaterial surfaces using ECM coatings such as fibronectin extracted from animal-derived ECM have contributed significantly to tissue regenerative engineering as well as basic cell biology research. Additionally, synthetic and natural bioadhesive agents with pronounced abilities to enhance adhesion in numerous biological components and molecules have also been assessed in the field of tissue regeneration. Research into the use of facilitative bioadhesives has aimed to further optimize the biocompatibility, biodegradability, toxicity levels, and crosslinking duration of bioadhesive materials for improved targeted delivery and tissue repair. However, the restrictive drawbacks of some of these bioadhesive and animal-derived materials include the potential risk of disease transmission, immunogenicity, poor reproducibility, impurities, and instability. Therefore, it is necessary for alternative strategies to be sought out to improve the quality of cell adhesion to biomaterials. One promising strategy involves the use of cell-adhesive small molecules. Small molecules are relatively inexpensive, stable, and low-molecular-weight (<1000 Da) compounds with great potential to serve as efficient alternatives to conventional bioadhesives, ECM proteins, and other derived peptides. Over the past few years, a number of cell adhesive small molecules with the potential for tissue regeneration have been reported. In this review, we discuss the current progress using cell adhesive small molecules to regulate tissue regeneration.
Comparison of Serum and Urine as Sources of miRNA Markers for the Detection of Ovarian Cancer
Authors: Kupec Tomas , Bleilevens Andreas , Klein Birgit , Hansen Thomas , Najjari Laila , Wittenborn Julia , Stickeler Elmar , Maurer Jochen
Published: September 2023

Ovarian cancer is the second most fatal gynecological cancer. Early detection, which could be achieved through widespread screening, has not yet had an impact on mortality. The aim of our pilot study was to investigate the expression of miRNAs analyzed by a human miRNA microarray chip in urine and serum of patients with ovarian cancer. We analyzed three serum and three urine samples from healthy donors and five serum and five urine samples from patients with ovarian cancer taken at first diagnosis, before any treatment. We selected the seven miRNAs with the highest expression fold change in the microarray chip (cancer vs. control) in urine and serum, for validation by qPCR. We were able to validate two of the seven miRNAs in serum. In contrast to these findings, we were able to validate all of the top seven miRNAs identified in urine using qPCR. The top seven miRNAs in urine identified by microarray chip showed significantly greater differences in expression between patients with ovarian cancer and healthy donors compared to serum. Based on our finding, we can suggest that urine as a biomaterial is more suitable than serum for miRNA profiling by microarray chip in the search for new biomarkers in ovarian cancer.
The Effects of Biologics on Hematologic Malignancy Development in Patients with Ankylosing Spondylitis, Psoriasis, or Psoriatic Arthritis: A National Cohort Study
Authors: Tsai Chia-Jung , Lin Yu-Chih , Chen Chung-Yu , Hung Chih-Hsing , Lin Yi-Ching
Published: September 2023

Biologics are used for ankylosing spondylitis (AS), psoriasis, and psoriatic arthritis (PsA) treatment. The association between biologics and the development of hematologic malignancies is controversial, and data on patients with AS, psoriasis, and PsA are scarce. This retrospective cohort study used data from 2010 to 2020 from Taiwan’s National Health Insurance Research Database (NHIRD). Patients with AS, psoriasis, and PsA were divided into a biologics and non biologics group after 1:10 propensity score matching. The hematologic malignancy incidences and the time-/dose-dependent effects on biologics were analyzed by Poisson regression to evaluate the incidence rate ratio (IRR). Of the 4157 biologics users and 38,399 non biologics users included in the study, 10 and 72 persons developed hematologic malignancies, respectively. Biologics only significantly increased the risk of hematologic malignancies in non-Hodgkin’s lymphoma (IRR: 2.48, 95% confidence interval (CI): 1.28–4.80). Different treatment patterns, types of biologics prescribed, cumulative defined daily doses, comorbidities, and comedications did not significantly affect hematologic malignancy development. A significantly increased risk was observed when biologics had been prescribed for 1–2 years (IRR: 2.95, 95% CI: 1.14–7.67). Clinical professionals should be aware of a patients’ risk of hematologic malignancies during the second year of biologic treatment.
Preparation and Characterization of Nano-Silver-Loaded Antibacterial Membrane via Coaxial Electrospinning
Authors: Hu Qingxi , Huang Zhenwei , Zhang Haiguang , Ramalingam Murugan
Published: September 2023

The coaxial electrospinning process has been widely used in the biomedical field, and its process parameters affect product quality seriously. In this paper, the influence of key process parameters of coaxial electrostatic spinning (solution concentration, electrospinning voltage, acceptance distance and liquid supply velocity) on the preparation of a membrane with Chitosan, Polyethylene oxide and nano-silver as the core layer and Polycaprolactone as the shell layer was studied. The optimal combination of key process parameters was obtained by using an orthogonal test, scanning electron microscope, transmission electron microscope and macro-characterization diagram. The results showed that the coaxial electrospun membrane had good mechanical properties (tensile strength is about 2.945 Mpa), hydrophilicity (the water contact angle is about 72.28°) and non-cytotoxicity, which was conducive to cell adhesion and proliferation. The coaxial electrospun membrane with nano-silver has an obvious inhibitory effect on Escherichia coli and Staphylococcus aureus. In summary, the coaxial electrospun membrane that we produced is expected to be used in clinical medicine, such as vascular stent membranes and bionic blood vessels.
3D-Printed Tumor-on-a-Chip Model for Investigating the Effect of Matrix Stiffness on Glioblastoma Tumor Invasion
Authors: Amereh Meitham , Seyfoori Amir , Dallinger Briana , Azimzadeh Mostafa , Stefanek Evan , Akbari Mohsen
Published: September 2023

Glioblastoma multiform (GBM) tumor progression has been recognized to be correlated with extracellular matrix (ECM) stiffness. Dynamic variation of tumor ECM is primarily regulated by a family of enzymes which induce remodeling and degradation. In this paper, we investigated the effect of matrix stiffness on the invasion pattern of human glioblastoma tumoroids. A 3D-printed tumor-on-a-chip platform was utilized to culture human glioblastoma tumoroids with the capability of evaluating the effect of stiffness on tumor progression. To induce variations in the stiffness of the collagen matrix, different concentrations of collagenase were added, thereby creating an inhomogeneous collagen concentration. To better understand the mechanisms involved in GBM invasion, an in silico hybrid mathematical model was used to predict the evolution of a tumor in an inhomogeneous environment, providing the ability to study multiple dynamic interacting variables. The model consists of a continuum reaction–diffusion model for the growth of tumoroids and a discrete model to capture the migration of single cells into the surrounding tissue. Results revealed that tumoroids exhibit two distinct patterns of invasion in response to the concentration of collagenase, namely ring-type and finger-type patterns. Moreover, higher concentrations of collagenase resulted in greater invasion lengths, confirming the strong dependency of tumor behavior on the stiffness of the surrounding matrix. The agreement between the experimental results and the model’s predictions demonstrates the advantages of this approach in investigating the impact of various extracellular matrix characteristics on tumor growth and invasion.
Unraveling Interconnections: Analyzing the Impact of a Founder’s Characteristics on Business Growth Strategy
Authors: Liu Ying , Polkinghorne Martyn
Published: September 2023

This study examines the influence of founder characteristics on the selection of business growth strategies in companies undergoing an initial public offering (IPO). The research is based upon quantitative analysis of data from entrepreneur-led IPOs on the London Stock Exchange. The study investigates the impact of founder’s work experience, external directorships, education, age, ownership, and the presence of a founder–CEO, on the choice between mergers and acquisitions (M&A) and research and development (R&D) as growth strategies. The results show that founders with a throughput functional background and extensive external directorships are more likely to adopt M&A as a growth strategy. Moreover, founders with higher education levels and a PhD are more inclined towards R&D investment. The findings also suggest that older founders are more likely to invest in R&D, whilst higher levels of ownership tends to deter R&D expenditure. Interestingly, the presence of a founder–CEO is associated with a lower likelihood of investing in R&D and a higher propensity for M&A, although these correlations are not statistically significant. These results shed light on the influence of founder characteristics on strategic decision-making during the IPO stage and provide implications for understanding the dynamics of business growth strategies in transitioning companies.
Accounting for Climate When Determining the Impact of Weather on Retail Sales
Authors: Dimitrov Stanko , Chenavaz Régis Y. , Escobar Octavio
Published: September 2023

In this paper, we explore the importance of accounting for climate when determining the impact of weather on product sales. Using a France-wide scanner panel dataset provided by our industry partner, we show that if climate is not accounted for, product categories may be misclassified as being weather sensitive when they are not, and vice versa. This is motivated by previous research and industry reports that suggest a relationship between weather and retail sales. However, these studies often fail to distinguish between weather and climate, leading to inaccurate conclusions. Our results highlight the need to control for climate in order to accurately assess the effects of weather on retail sales. We use ordinary least squares regression to estimate the relationship between temperature and sales for 29 different product categories. The regression models control for various factors, including shelf space allocation, week of observation, quantity purchased, promotion, store brand, store surface area, store competition, and consumer behavior measures. We find that when accounting for climate, only a subset of the product categories is sensitive to weather. Additionally, we show that climate can be approximated using a week index, eliminating the need for additional data collection and approximation efforts. Our findings have implications for both researchers and practitioners. Researchers should be aware of the importance of accounting for climate when studying the impact of weather on retail sales, as failing to do so may lead to erroneous conclusions. Practitioners can use our results to inform their marketing and sales strategies, taking into account the weather sensitivity of different product categories and the role of climate in shaping consumer behavior. Overall, our study emphasizes the need to consider climate when determining the impact of weather on retail sales, and provides practical insights for retailers and economists.
Neoadjuvant Intratumoral Immunotherapy with Cowpea Mosaic Virus Induces Local and Systemic Antitumor Efficacy in Canine Mammary Cancer Patients
Authors: Valdivia Guillermo , Alonso-Miguel Daniel , Perez-Alenza Maria Dolores , Zimmermann Anna Barbara Emilia , Schaafsma Evelien , Kolling Fred W. , Barreno Lucia , Alonso-Diez Angela , Beiss Veronique , Affonso de Oliveira Jessica Fernanda , Suárez-Redondo María , Fiering Steven , Steinmetz Nicole F. , vom Berg Johannes , Peña Laura , Arias-Pulido Hugo
Published: September 2023

The lack of optimal models to evaluate novel agents is delaying the development of effective immunotherapies against human breast cancer (BC). In this prospective open label study, we applied neoadjuvant intratumoral immunotherapy with empty cowpea mosaic virus-like particles (eCPMV) to 11 companion dogs diagnosed with canine mammary cancer (CMC), a spontaneous tumor resembling human BC. We found that two neoadjuvant intratumoral eCPMV injections resulted in tumor reduction in injected tumors in all patients and in noninjected tumors located in the ipsilateral and contralateral mammary chains of injected dogs. Tumor reduction was independent of clinical stage, tumor size, histopathologic grade, and tumor molecular subtype. RNA-seq-based analysis of injected tumors indicated a decrease in DNA replication activity and an increase in activated dendritic cell infiltration in the tumor microenvironment. Immunohistochemistry analysis demonstrated significant intratumoral increases in neutrophils, T and B lymphocytes, and plasma cells. eCPMV intratumoral immunotherapy demonstrated antitumor efficacy without any adverse effects. This novel immunotherapy has the potential for improving outcomes for human BC patients.
Metal Halide Perovskite Light-Emitting Transistor with Tunable Emission Based on Electrically Doped Semiconductor Nanocrystal-Based Microcavities
Authors: Scotognella Francesco
Published: September 2023

Electroluminescence of metal halide perovskites has been widely reported via the fabrication and optimization of light-emitting diodes and light-emitting transistors. Light-emitting transistors are particularly interesting owing to the additional control of the gate voltage on the electroluminescence. In this work, the design of a microcavity, with a defect mode that can be tuned with an applied voltage, integrated with a metal halide light-emitting transistor is shown. The optical properties of the device have been simulated with the transfer matrix method, considering the wavelength-dependent refractive indexes of all the employed materials. The tunability of the microcavity has been obtained via the employment of doped semiconductor nanocrystalline films, which show a tunable plasma frequency and, thus, a tunable refractive index as a function of the applied voltage. Consequently, the tunability of the electroluminescence of the metal halide perovskite light-emitting transistor has been demonstrated.
Expanding Heteroaromatic and 2-Aminosugar Chemical Space Accessible from the Biopolymer Chitin
Authors: Rossa Thaís A. , Neville Jessica C. , Jun Seongmin Paul , Söhnel Tilo , Sperry Jonathan
Published: September 2023

Herein, we report the expansion of chemical space available from chitin, accessible via the biogenic N-platforms 3A5AF, M4A2C, and di-HAF. The biologically active heteroaromatics furo[3,2-d]pyrimidin-4-one and furo[3,2-d]pyrimidin-4-amine can be selectively accessed from 3A5AF and M4A2C, respectively. The chiral pool synthon di-HAF is a viable substrate for Achmatowicz rearrangement, providing streamlined access to 2-aminosugars possessing a versatile hydroxymethyl group at C5.
Chemical Sensing and Analysis with Optical Nanostructures
Authors: Dong Chenyu , Wang Yifan , Zhao Xiaoyan , Bian Jie , Zhang Weihua
Published: September 2023

Nanostructures and nanomaterials, especially plasmonic nanostructures, often show optical properties that conventional materials lack and can manipulate light, as well as various light–matter interactions, in both their near-field and far-field regions with a high efficiency. Thanks to these unique properties, not only can they be used to enhance the sensitivity of chemical sensing and analysis techniques, but they also provide a solution for designing new sensing devices and simplifying the design of analytical instruments. The earliest applications of optical nanostructures are surface-enhanced spectroscopies. With the help of the resonance field enhancement of plasmonic nanostructures, molecular signals, such as Raman, infrared absorption, and fluorescence can be significantly enhanced, and even single-molecule analysis can be realized. Moreover, the resonant field enhancements of plasmonic nanostructures are often associated with other effects, such as optical forces, resonance shifts, and photothermal effects. Using these properties, label-free plasmonic sensors, nano-optical tweezers, and plasmonic matrix-assisted laser desorption/ionization have also been demonstrated in the past two decades. In the last few years, the research on optical nanostructures has gradually expanded to non-periodic 2D array structures, namely metasurfaces. With the help of metasurfaces, light can be arbitrarily manipulated, leading to many new possibilities for developing miniaturized integrated intelligent sensing and analysis systems. In this review, we discuss the applications of optical nanostructures in chemical sensing and analysis from both theoretical and practical aspects, aiming at a concise and unified framework for this field.
The Feeling of Pleasure for Overweight Children during Different Types of Physical Activity
Authors: Hawani Aymen , Chikha Anis , Souissi Mohamed , Trabelsi Omar , Mrayah Maher , Souissi Nizar , Marsigliante Santo , Muscella Antonella
Published: September 2023

The feeling of pleasure during physical education (PE) could increase with physical activity participation and adherence for overweight children. While traditional games are known to have positive benefits on motor skill development, especially for children with poorer motor skills, and on the body mass of children, little is known about overweight children’s feelings of enjoyment when playing these games. To identify a program of physical activity appreciated by overweight children, we tested the effect of different activities, namely soccer (SO), shot put (SP), and traditional motor games (TMGs), on the feelings of pleasure for 28 overweight male children (aged 12.11 ± 0.63 years, BMI 26.89 ± 0.15 kg·m−2) participating in a 3-month cross-over study. To measure affective responses to exercises, we applied a validated feeling scale. The data were collected during eight PE lessons, which were organized for each cycle taught. Post hoc pairwise comparisons revealed a significant difference (Z = −3.195, p < 0.01) between the mean feeling score reported after the SO cycle (2.48 ± 0.41) and that after the TMGs (3.04 ± 0.32). A similar significant difference (Z = −3.304, p < 0.01) was found between the mean feeling scores reported after the SP cycle (2.27 ± 0.32) and the TMGs (3.04 ± 0.32). There was no significant difference between the mean feeling scores reported after the SO (2.48 ± 0.41) and SP cycles (2.27 ± 0.32). In conclusion, the findings of the present study suggest that TMGs may have beneficial effects on the feelings of pleasure for overweight children. Therefore, TMGs might potentially be considered as an alternative to conventional physical activities.
Similarities and Differences between Multisystem Inflammatory Syndrome in Children (MIS-C) and Kawasaki Disease Shock Syndrome
Authors: Lee Jin , Kim Beom Joon , Cho Kyoung-Soon , Rhim Jung Woo , Lee Soo-Young , Jeong Dae Chul
Published: September 2023

This study aimed to investigate the characteristics of COVID-19-associated multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease shock syndrome (KDSS) and to compare the similarities and differences between the two diseases. The incidence of KDSS and MIS-C was also estimated. Medical records of patients diagnosed with MIS-C or KDSS at four hospitals from January 2013 to December 2022 were retrospectively reviewed. Thirty-one patients were enrolled in the study in either an MIS-C group (n = 22) or a KDSS group (n = 9). The incidence of KDSS in KD was 0.8% (9/1095) and the incidence of MIS-C versus KD was 10.2% (22/216). Compared with the MIS-C group, the KDSS group had longer hospital stays and more severe systemic inflammation (e.g., anemia, elevated C-reactive protein, hypoalbuminemia, and pyuria) and organ dysfunction (e.g., number of involved organs, shock, vasoactive infusion, and intensive care unit admission). All patients in the MIS-C group, but none in the KDSS group, including two patients during the COVID-19 pandemic, had laboratory evidence of SARS-CoV-2 infection. MIS-C and KDSS shared demographic, clinical, and laboratory characteristics; organ dysfunction; treatment; and outcomes. Overall severity was more severe in patients with KDSS than in those with MIS-C. The most important difference between MIS-C and KDSS was whether SARS-CoV-2 was identified as an infectious trigger.
Psychometric Properties of the Italian Version of the Toileting Habit Profile Questionnaire-Revised (THPQ-R) in Children with Autism Spectrum Disorder
Authors: Berardi Anna , Galeoto Giovanni , Ruffini Martina , Simeon Rachele , González-Bernal Jerónimo , Seco-Calvo Jesús Angel
Published: September 2023

Introduction: Children with autism spectrum disorder (ASD) often seem not to feel the need to go to the bathroom in whatever context they are in and may suffer from hypo-responsiveness. Recent studies show a correlation between sensory problems, constipation, and fecal incontinence in children. This requires an assessment tool to identify evacuation issues in children with sensory dysfunction. Therefore, the purpose of this study is to validate the Italian version of The Toileting Habit Profile Questionnaire-Revised (THPQ-R) in children with ASD. Methods: The inclusion criteria were a confirmed diagnosis of ASD and an age between 3 and 8 years old. The Toileting Habit Profile Questionnaire Revised (THPQ-R) was recently validated in the Italian language on a healthy population. The Italian version has 17 items with two alternative response options, frequently/always or never/rarely, based on how often the behavior occurs. The THPQ-R questionnaire is easy to administer, interpret, and manage. For concurrent validity, we used the Italian version of the Sensory Processing Measure and Sensory Processing Measure—Preschool. Results: For the THPQ-R validation, 43 participants were recruited. The internal consistency, reporting an α value of 0.763, showed that the THPQ-R was a very reliable scale. The THPQ-R appears to be correlated only with the domains “Social Participation T-point”, “Hearing T-point”, and “Planning and Ideas T-point”. However, these correlations are not statistically significant. Conclusion: The THPQ-R highlights positive results regarding validity and reliability and shows a positive correlation between defecation disorders and social participation.
The Journey to Sustainable Participation in Physical Activity for Adolescents Living with Cerebral Palsy
Authors: Kilgour Gaela , Stott Ngaire Susan , Steele Michael , Adair Brooke , Hogan Amy , Imms Christine
Published: September 2023

Purpose: To understand adolescents’ and their parents’ perspectives on ‘being active’, this study explored the experience of participation in physical activity (PA), the role of long-term participation in PA, and the importance of remaining active for life. Methods: Eight ambulant adolescents with CP (aged 11–16 years, seven male) participated in a high-level mobility programme twice per week for 12 weeks. Guided using interpretive description, adolescents and 12 of their parents were interviewed before, after and nine months following the programme. Thirty-eight interviews were coded, analysed, and interpreted, informed by audit information, reflective journaling, and team discussions. Results: Adolescents and their parents highly value being active now and into adulthood. Sustainable participation in PA requires adolescents and families to navigate complex environments (interpersonal, organisational, community, and policy). Core themes were: ‘Just Doing it’, ‘Getting the Mix Right’ (right people, right place, right time), ‘Balancing the Continua’ and ‘Navigating the Systems’. The continua involved balancing intra-personal attributes: ‘I will try anything’ through to ‘I will do it if I want to’ and ‘It’s OK to be different’ through to ‘It sucks being disabled’. Conclusions: The journey to sustainable participation was complex and dynamic. Experiences of successful journeys are needed to help adolescents with CP “stay on track” to sustainable participation.
Enhancing Handwriting Performance of Children with Developmental Coordination Disorder (DCD) Using Computerized Visual Feedback
Authors: Bartov Rachel , Wagner Michael , Shvalb Nir , Hochhauser Michal
Published: September 2023

Recent studies have analyzed the writing metrics of children with developmental coordination disorder (DCD) using computerized systems. To date, the use of computerized visual feedback to improve handwriting has not been investigated. This study aimed to examine the effects of computerized visual feedback on handwriting performance in time, spatial orientation, and pressure indices for children with DCD. Twenty-seven children aged 7 to 12 years with DCD assessed by the Movement Assessment Battery for Children and the Developmental Coordination Disorder Questionnaire received one weekly intervention session for 8 weeks, during which they twice copied an excerpt onto a tablet. Once, they received visual feedback where the writing color corresponded to the degree of pressure on the writing surface, and once they received no visual feedback. The two conditions were counterbalanced throughout the sessions. Pre-intervention sessions were compared with post-intervention sessions and with new texts for time, spatial orientation, and pressure measures. The findings revealed significantly decreased total and mean letter writing, in-air, and writing time and increased capacity in the visual feedback condition. In the spatial variables, a significant decrease in letter height variance was found. Pressure increased significantly throughout the intervention with visual feedback, whereas it decreased post-test in the writing task in both conditions and was maintained in the new text. Visual feedback intervention can increase the kinesthetic–haptic feedback required to regulate pressure during writing, promoting more efficient feedforward processes and improving output quality and capacity. The training effectiveness was transferable, and the intervention accessibility could increase student autonomy.
Identifying Network Biomarkers in Early Diagnosis of Hepatocellular Carcinoma via miRNA–Gene Interaction Network Analysis
Authors: Yang Zhiyuan , Qi Yuanyuan , Wang Yijing , Chen Xiangyun , Wang Yuerong , Zhang Xiaoli
Published: September 2023

Background: Hepatocellular carcinoma (HCC) is a highly heterogeneous cancer at the histological level. Despite the emergence of new biological technology, advanced-stage HCC remains largely incurable. The prediction of a cancer biomarker is a key problem for targeted therapy in the disease. Methods: We performed a miRNA–gene integrated analysis to identify differentially expressed miRNAs (DEMs) and genes (DEGs) of HCC. The DEM–DEG interaction network was constructed and analyzed. Gene ontology enrichment and survival analyses were also performed in this study. Results: By the analysis of healthy and tumor samples, we found that 94 DEGs and 25 DEMs were significantly differentially expressed in different datasets. Gene ontology enrichment analysis showed that these 94 DEGs were significantly enriched in the term “Liver” with a statistical p-value of 1.71 × 10−26. Function enrichment analysis indicated that these genes were significantly overrepresented in the term “monocarboxylic acid metabolic process” with a p-value = 2.94 × 10−18. Two sets (fourteen genes and five miRNAs) were screened by a miRNA–gene integrated analysis of their interaction network. The statistical analysis of these molecules showed that five genes (CLEC4G, GLS2, H2AFZ, STMN1, TUBA1B) and two miRNAs (hsa-miR-326 and has-miR-331-5p) have significant effects on the survival prognosis of patients. Conclusion: We believe that our study could provide critical clinical biomarkers for the targeted therapy of HCC.
A Systematic Review of Existing Early Warning Systems’ Challenges and Opportunities in Cloud Computing Early Warning Systems
Authors: Agbehadji Israel Edem , Mabhaudhi Tafadzwanashe , Botai Joel , Masinde Muthoni
Published: September 2023

This paper assessed existing EWS challenges and opportunities in cloud computing through the PSALSAR framework for systematic literature review and meta-analysis. The research used extant literature from Scopus and Web of Science, where a total of 2516 pieces of literature were extracted between 2004 and 2022, and through inclusion and exclusion criteria, the total was reduced to 98 for this systematic review. This review highlights the challenges and opportunities in transferring in-house early warning systems (that is, non-cloud) to the cloud computing infrastructure. The different techniques or approaches used in different kinds of EWSs to facilitate climate-related data processing and analytics were also highlighted. The findings indicate that very few EWSs (for example, flood, drought, etc.) utilize the cloud computing infrastructure. Many EWSs are not leveraging the capability of cloud computing but instead using online application systems that are not cloud-based. Secondly, a few EWSs have harnessed the computational techniques and tools available on a single platform for data processing. Thirdly, EWSs combine more than one fundamental tenet of the EWS framework to provide a holistic warning system. The findings suggest that reaching a global usage of climate-related EWS may be challenged if EWSs are not redesigned to fit the cloud computing service infrastructure.
Regional Contribution in Electrophysiological-Based Classifications of Attention Deficit Hyperactive Disorder (ADHD) Using Machine Learning
Authors: Chauhan Nishant , Choi Byung-Jae
Published: September 2023

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental condition in children and is characterized by challenges in maintaining attention, hyperactivity, and impulsive behaviors. Despite ongoing research, we still do not fully understand what causes ADHD. Electroencephalography (EEG) has emerged as a valuable tool for investigating ADHD-related neural patterns due to its high temporal resolution and non-invasiveness. This study aims to contribute to diagnostic accuracy by leveraging EEG data to classify children with ADHD and healthy controls. We used a dataset containing EEG recordings from 60 children with ADHD and 60 healthy controls. The EEG data were captured during cognitive tasks and comprised signals from 19 channels across the scalp. Our primary objective was to develop a machine learning model capable of distinguishing ADHD subjects from controls using EEG data as discriminatory features. We employed several well-known classifiers, including a support vector machine, random forest, decision tree, AdaBoost, Naive Bayes, and linear discriminant analysis, to discern distinctive EEG patterns. To further enhance classification accuracy, we explored the impact of regional data on the classification outcomes. We arranged the EEG data according to the brain regions from which they were derived (namely frontal, temporal, central, parietal, and occipital) and examined their collective effects on the accuracy of our classifications. Notably, we considered combinations of three regions at a time and found that certain combinations led to enhanced accuracy. Our findings underscore the potential of EEG-based classification in distinguishing children with ADHD from healthy controls. The Naive Bayes classifier yielded the highest accuracy (84%) when applied to specific region combinations. Moreover, we evaluated the classification performance based on hemisphere-specific EEG data and found promising results, particularly when using the right hemisphere region channels.