bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptomic Networks Reveal the Tissue-Specific Cold Shock Responses in Japanese Flounder (Paralichthys olivaceus)
Authors: He Jiayi , Zhu Qing , Han Ping , Zhou Tianyu , Li Juyan , Wang Xubo , Cheng Jie
Published: May 2023

Low temperature is among the important factors affecting the distribution, survival, growth, and physiology of aquatic animals. In this study, coordinated transcriptomic responses to 10 °C acute cold stress were investigated in the gills, hearts, livers, and spleens of Japanese flounder (Paralichthys olivaceus), an important aquaculture species in east Asia. Histological examination suggested different levels of injury among P. olivaceus tissues after cold shock, mainly in the gills and livers. Based on transcriptome and weighted gene coexpression network analysis, 10 tissue-specific cold responsive modules (CRMs) were identified, revealing a cascade of cellular responses to cold stress. Specifically, five upregulated CRMs were enriched with induced differentially expressed genes (DEGs), mainly corresponding to the functions of “extracellular matrix”, “cytoskeleton”, and “oxidoreductase activity”, indicating the induced cellular response to cold shock. The “cell cycle/division” and “DNA complex” functions were enriched in the downregulated CRMs for all four tissues, which comprised inhibited DEGs, suggesting that even with tissue-specific responses, cold shock may induce severely disrupted cellular functions in all tissues, reducing aquaculture productivity. Therefore, our results revealed the tissue-specific regulation of the cellular response to low-temperature stress, which warrants further investigation and provides more comprehensive insights for the conservation and cultivation of P. olivaceus in cold water.
RPS27a and RPL40, Which Are Produced as Ubiquitin Fusion Proteins, Are Not Essential for p53 Signalling
Authors: Eastham Matthew John , Pelava Andria , Wells Graeme Raymond , Watkins Nicholas James , Schneider Claudia
Published: May 2023

Two of the four human ubiquitin-encoding genes express ubiquitin as an N-terminal fusion precursor polypeptide, with either ribosomal protein (RP) RPS27a or RPL40 at the C-terminus. RPS27a and RPL40 have been proposed to be important for the induction of the tumour suppressor p53 in response to defects in ribosome biogenesis, suggesting that they may play a role in the coordination of ribosome production, ubiquitin levels and p53 signalling. Here, we report that RPS27a is cleaved from the ubiquitin-RP precursor in a process that appears independent of ribosome biogenesis. In contrast to other RPs, the knockdown of either RPS27a or RPL40 did not stabilise the tumour suppressor p53 in U2OS cells. Knockdown of neither protein blocked p53 stabilisation following inhibition of ribosome biogenesis by actinomycin D, indicating that they are not needed for p53 signalling in these cells. However, the knockdown of both RPS27a and RPL40 in MCF7 and LNCaP cells robustly induced p53, consistent with observations made with the majority of other RPs. Importantly, RPS27a and RPL40 are needed for rRNA production in all cell lines tested. Our data suggest that the role of RPS27a and RPL40 in p53 signalling, but not their importance in ribosome biogenesis, differs between cell types.
Pharmacological Inhibition of Gasdermin D Suppresses Angiotensin II-Induced Experimental Abdominal Aortic Aneurysms
Authors: Guo Jia , Shi Jinyun , Qin Min , Wang Yan , Li Zhidong , Shoji Takahiro , Ikezoe Toru , Ge Yingbin , Xu Baohui
Published: May 2023

Background: Gasdermin D, a molecule downstream of the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing inflammasome, forms the membrane pore for the secretion of interleukin (IL)-1β and IL-18, and also mediates pyroptosis. This study was to explore the influence of treatment with disulfiram, a small molecule inhibitor to gasdermin D, on the formation and progression of experimental abdominal aortic aneurysms (AAA). Methods: AAAs were induced in 10-week-old male apolipoprotein E deficient mice by subcutaneous infusion of angiotensin II (1000 ng/min/kg body weight) for 28 days via osmotic minipumps. Three days prior to angiotensin II infusion, disulfiram (50 mg/kg) or an equal volume of saline as the vehicle control was administered daily via oral gavage. The influence on experimental AAAs was analyzed by serial measurements of aortic diameters via ultrasonography, grading AAA severity and histopathology at sacrifice. Serum IL-1β and IL-18 levels, systolic blood pressure, total cholesterol, and triglyceride were also measured. Additional experiments assayed the influences on the cell viability and IL-1β secretion of in vitro activated macrophages. Results: Disulfiram significantly reduced the enlargement, incidence, and severity of angiotensin II-induced experimental AAAs with attenuation of medial elastin breaks, mural macrophage accumulation, and systolic blood pressure. The AAA suppression was also associated with reduced systemic levels of IL-1β but not IL-18. However, disulfiram treatment had no impact on body weight gain and lipid levels in aneurysmal mice. Additionally, disulfiram treatment also markedly reduced the secretion of IL-1β from activated macrophages with a limited effect on cell viability in vitro. Conclusions: Gasdermin D inhibition by disulfiram attenuated angiotensin II-induced experimental AAAs with reduced systemic IL-1β levels and in vitro activated macrophage IL-1β secretion. Our study suggests that pharmacological gasdermin D inhibition may have translational potential for limiting clinical AAA progression.
3D Organoids for Regenerative Endodontics
Authors: Li Fang-Chi , Kishen Anil
Published: May 2023

Apical periodontitis is the inflammation and destruction of periradicular tissues, mediated by microbial factors originating from the infected pulp space. This bacteria-mediated inflammatory disease is known to interfere with root development in immature permanent teeth. Current research on interventions in immature teeth has been dedicated to facilitating the continuation of root development as well as regenerating the dentin–pulp complex, but the fundamental knowledge on the cellular interactions and the role of periapical mediators in apical periodontitis in immature roots that govern the disease process and post-treatment healing is limited. The limitations in 2D monolayer cell culture have a substantial role in the existing limitations of understanding cell-to-cell interactions in the pulpal and periapical tissues. Three-dimensional (3D) tissue constructs with two or more different cell populations are a better physiological representation of in vivo environment. These systems allow the high-throughput testing of multi-cell interactions and can be applied to study the interactions between stem cells and immune cells, including the role of mediators/cytokines in simulated environments. Well-designed 3D models are critical for understanding cellular functions and interactions in disease and healing processes for future therapeutic optimization in regenerative endodontics. This narrative review covers the fundamentals of (1) the disease process of apical periodontitis; (2) the influence and challenges of regeneration in immature roots; (3) the introduction of and crosstalk between mesenchymal stem cells and macrophages; (4) 3D cell culture techniques and their applications for studying cellular interactions in the pulpal and periapical tissues; (5) current investigations on cellular interactions in regenerative endodontics; and, lastly, (6) the dental–pulp organoid developed for regenerative endodontics.
Age-Dependent Alterations in Platelet Mitochondrial Respiration
Authors: Fišar Zdeněk , Hroudová Jana , Zvěřová Martina , Jirák Roman , Raboch Jiří , Kitzlerová Eva
Published: May 2023

Mitochondrial dysfunction is an important cellular hallmark of aging and neurodegeneration. Platelets are a useful model to study the systemic manifestations of mitochondrial dysfunction. To evaluate the age dependence of mitochondrial parameters, citrate synthase activity, respiratory chain complex activity, and oxygen consumption kinetics were assessed. The effect of cognitive impairment was examined by comparing the age dependence of mitochondrial parameters in healthy individuals and those with neuropsychiatric disease. The study found a significant negative slope of age-dependence for both the activity of individual mitochondrial enzymes (citrate synthase and complex II) and parameters of mitochondrial respiration in intact platelets (routine respiration, maximum capacity of electron transport system, and respiratory rate after complex I inhibition). However, there was no significant difference in the age-related changes of mitochondrial parameters between individuals with and without cognitive impairment. These findings highlight the potential of measuring mitochondrial respiration in intact platelets as a means to assess age-related mitochondrial dysfunction. The results indicate that drugs and interventions targeting mitochondrial respiration may have the potential to slow down or eliminate certain aging and neurodegenerative processes. Mitochondrial respiration in platelets holds promise as a biomarker of aging, irrespective of the degree of cognitive impairment.
The First Large Deletion of ATL3 Identified in a Patient Presenting with a Sensory Polyneuropathy
Authors: Pyromali Ioanna , Richard Laurence , Derouault Paco , Vallat Jean-Michel , Ghorab Karima , Magdelaine Corinne , Sturtz Franck , Favreau Frédéric , Lia Anne-Sophie
Published: May 2023

Hereditary sensory neuropathies (HSN) are a heterogenous group of sensory neuropathies. Mutations in ATL3 have been described in patients presenting with hereditary sensory neuropathy IF (HSN1F), a subtype of HSN. Herein, by analyzing targeted-NGS data of a patient presenting with sensory neuropathy symptoms using the CovCopCan bioinformatic tool, we discovered the presence of a deletion of around 3kb in ATL3 from Chr11:63,401,422 to Chr11:63,398,182. This deletion affects ATL3 exons 11 and 12 and could lead to the mutation c.(1036-861_1539+329del), p.(Ala346_Gln513del). In addition, an analysis of the breakpoints’ sequences revealed the presence of Alu transposable elements at the position of the breakpoints, which pointed to a possible erroneous recombination event following a non-allelic-homologous-recombination mechanism in this area. Moreover, electronic microscopy analysis of the patient’s nerve biopsy revealed a severe rarefaction of the myelinated fibers, a demyelinating–remyelinating process, and an abnormal aspect of the endoplasmic reticulum. These findings suggest that this structural variation could potentially be responsible for the HSN symptoms of the patient. Research of structural variations in ATL3 in numerous other patients presenting similar symptoms should be broadly investigated in order to improve patients’ diagnoses.
A Computer-Aided Diagnostic System to Identify Diabetic Retinopathy, Utilizing a Modified Compact Convolutional Transformer and Low-Resolution Images to Reduce Computation Time
Authors: Khan Inam Ullah , Raiaan Mohaimenul Azam Khan , Fatema Kaniz , Azam Sami , Rashid Rafi ur , Mukta Saddam Hossain , Jonkman Mirjam , De Boer Friso
Published: May 2023

Diabetic retinopathy (DR) is the foremost cause of blindness in people with diabetes worldwide, and early diagnosis is essential for effective treatment. Unfortunately, the present DR screening method requires the skill of ophthalmologists and is time-consuming. In this study, we present an automated system for DR severity classification employing the fine-tuned Compact Convolutional Transformer (CCT) model to overcome these issues. We assembled five datasets to generate a more extensive dataset containing 53,185 raw images. Various image pre-processing techniques and 12 types of augmentation procedures were applied to improve image quality and create a massive dataset. A new DR-CCTNet model is proposed. It is a modification of the original CCT model to address training time concerns and work with a large amount of data. Our proposed model delivers excellent accuracy even with low-pixel images and still has strong performance with fewer images, indicating that the model is robust. We compare our model’s performance with transfer learning models such as VGG19, VGG16, MobileNetV2, and ResNet50. The test accuracy of the VGG19, ResNet50, VGG16, and MobileNetV2 were, respectively, 72.88%, 76.67%, 73.22%, and 71.98%. Our proposed DR-CCTNet model to classify DR outperformed all of these with a 90.17% test accuracy. This approach provides a novel and efficient method for the detection of DR, which may lower the burden on ophthalmologists and expedite treatment for patients.
Immunological and Metabolic Causes of Infertility in Polycystic Ovary Syndrome
Authors: Kicińska Aleksandra Maria , Maksym Radoslaw B. , Zabielska-Kaczorowska Magdalena A. , Stachowska Aneta , Babińska Anna
Published: May 2023

Infertility has been recognized as a civilizational disease. One of the most common causes of infertility is polycystic ovary syndrome (PCOS). Closely interrelated immunometabolic mechanisms underlie the development of this complex syndrome and lead to infertility. The direct cause of infertility in PCOS is ovulation and implantation disorders caused by low-grade inflammation of ovarian tissue and endometrium which, in turn, result from immune and metabolic system disorders. The systemic immune response, in particular the inflammatory response, in conjunction with metabolic disorders, insulin resistance (IR), hyperadrenalism, insufficient secretion of progesterone, and oxidative stress lead not only to cardiovascular diseases, cancer, autoimmunity, and lipid metabolism disorders but also to infertility. Depending on the genetic and environmental conditions as well as certain cultural factors, some diseases may occur immediately, while others may become apparent years after an infertility diagnosis. Each of them alone can be a significant factor contributing to the development of PCOS and infertility. Further research will allow clinical management protocols to be established for PCOS patients experiencing infertility so that a targeted therapy approach can be applied to the factor underlying and driving the “vicious circle” alongside symptomatic treatment and ovulation stimulation. Hence, therapy of fertility for PCOS should be conducted by interdisciplinary teams of specialists as an in-depth understanding of the molecular relationships and clinical implications between the immunological and metabolic factors that trigger reproductive system disorders is necessary to restore the physiology and homeostasis of the body and, thus, fertility, among PCOS patients.
Serum Asprosin Correlates with Indirect Insulin Resistance Indices
Authors: Mirr Małgorzata , Braszak-Cymerman Anna , Ludziejewska Aleksandra , Kręgielska-Narożna Matylda , Bogdański Paweł , Bryl Wiesław , Owecki Maciej
Published: May 2023

Background and Objectives: Insulin resistance is a major contributor to the development of type 2 diabetes and can be assessed using indirect indicators calculated from non-invasive tests. Asprosin is a recently discovered adipokine with a postulated effect on glycemic regulation. This study aimed to investigate the correlation between serum asprosin levels and insulin resistance indices. The correlation between circulating asprosin and obesity indices was also investigated. Materials and Methods: A total of 50 non-diabetic patients with obesity and 50 healthy volunteers were studied. Laboratory data, including circulating asprosin and anthropometric data, were collected. The following insulin resistance indices were calculated: triglyceride–glucose index (TyG), TyG–neck circumference (TyG–NC), TyG–neck circumference to height ratio (TyG–NHtR), TyG–waist circumference (TyG–WC), TyG–waist to height ratio (TyG–WHtR), TyG–body mass index (TyG–BMI), and the ratio between triglycerides and high-density cholesterol (TG/HDLc). The obtained data were analyzed separately for males and females. Results: Asprosin concentrations were significantly higher in obese patients (p < 0.001). Asprosin concentrations positively correlated with body mass index (p < 0.001, r = 0.8 in females and r = 0.8 in males), waist circumference (p < 0.001, r = 0.73 in females and r = 0.81 in males), and all tested indices of insulin resistance. The strongest correlation was observed for TyG–BMI (p < 0.001, r = 0.78 in females and r = 0.81 in males). Circulating asprosin was higher in females (p < 0.001). Conclusions: Asprosin can be considered a marker of obesity and insulin resistance.
Gut-on-a-Chip Research for Drug Development: Implications of Chip Design on Preclinical Oral Bioavailability or Intestinal Disease Studies
Authors: Donkers Joanne M. , van der Vaart Jamie I. , van de Steeg Evita
Published: May 2023

The gut plays a key role in drug absorption and metabolism of orally ingested drugs. Additionally, the characterization of intestinal disease processes is increasingly gaining more attention, as gut health is an important contributor to our overall health. The most recent innovation to study intestinal processes in vitro is the development of gut-on-a-chip (GOC) systems. Compared to conventional in vitro models, they offer more translational value, and many different GOC models have been presented over the past years. Herein, we reflect on the almost unlimited choices in designing and selecting a GOC for preclinical drug (or food) development research. Four components that largely influence the GOC design are highlighted, namely (1) the biological research questions, (2) chip fabrication and materials, (3) tissue engineering, and (4) the environmental and biochemical cues to add or measure in the GOC. Examples of GOC studies in the two major areas of preclinical intestinal research are presented: (1) intestinal absorption and metabolism to study the oral bioavailability of compounds, and (2) treatment-orientated research for intestinal diseases. The last section of this review presents an outlook on the limitations to overcome in order to accelerate preclinical GOC research.
Iodide-Mediated Etching of Gold Nanostar for the Multicolor Visual Detection of Hydrogen Peroxide
Authors: Lai Yunping , Yu Beirong , Lin Tianran , Hou Li
Published: May 2023

A multicolor visual method for the detection of hydrogen peroxide (H2O2) was reported based on the iodide-mediated surface etching of gold nanostar (AuNS). First, AuNS was prepared by a seed-mediated method in a HEPES buffer. AuNS shows two different LSPR absorbance bands at 736 nm and 550 nm, respectively. Multicolor was generated by iodide-mediated surface etching of AuNS in the presence of H2O2. Under the optimized conditions, the absorption peak Δλ had a good linear relationship with the concentration of H2O2 with a linear range from 0.67~66.67 μmol L−1, and the detection limit is 0.44 μmol L−1. It can be used to detect residual H2O2 in tap water samples. This method offered a promising visual method for point-of-care testing of H2O2-related biomarkers.
Recent Advances in Conjugated Polymer-Based Biosensors for Virus Detection
Authors: Nguyen Thanh Ngoc , Phung Viet-Duc , Tran Vinh Van
Published: May 2023

Nowadays, virus pandemics have become a major burden seriously affecting human health and social and economic development. Thus, the design and fabrication of effective and low-cost techniques for early and accurate virus detection have been given priority for prevention and control of such pandemics. Biosensors and bioelectronic devices have been demonstrated as promising technology to resolve the major drawbacks and problems of the current detection methods. Discovering and applying advanced materials have offered opportunities to develop and commercialize biosensor devices for effectively controlling pandemics. Along with various well-known materials such as gold and silver nanoparticles, carbon-based materials, metal oxide-based materials, and graphene, conjugated polymer (CPs) have become one of the most promising candidates for preparation and construction of excellent biosensors with high sensitivity and specificity to different virus analytes owing to their unique π orbital structure and chain conformation alterations, solution processability, and flexibility. Therefore, CP-based biosensors have been regarded as innovative technologies attracting great interest from the community for early diagnosis of COVID-19 as well as other virus pandemics. For providing precious scientific evidence of CP-based biosensor technologies in virus detection, this review aims to give a critical overview of the recent research related to use of CPs in fabrication of virus biosensors. We emphasize structures and interesting characteristics of different CPs and discuss the state-of-the-art applications of CP-based biosensors as well. In addition, different types of biosensors such as optical biosensors, organic thin film transistors (OTFT), and conjugated polymer hydrogels (CPHs) based on CPs are also summarized and presented.
Cognition and Consciousness Entwined
Authors: Grindrod Peter , Brennan Martin
Published: May 2023

We argue that cognition (information processing) and internal phenomenological sensations, including emotions, are intimately related and are not separable. We aver that phenomenological sensations are dynamical “modes” of firing behaviour that (i) exist over time and over large parts of the cortex’s neuron-to-neuron network and (ii) are consequences of the network-of-networks architecture, coupling the individual neuronal dynamics and the necessary time delay incurred by neuron-to-neuron transmission: if you possess those system properties, then you will have the dynamical modes and, thus, the phenomenological sensations. These modes are consequences of incoming external stimuli and are competitive within the system, suppressing and locking-out one another. On the other hand, the presence of any such mode acts as a preconditioner for the immediate (dynamic) cognitive processing of information. Thus, internal phenomenological sensations, including emotions, reduce the immediate decision set (of feasible interpretations) and hence the cognitive load. For organisms with such a mental inner life, there would clearly be a large cognitive evolutionary advantage, resulting in the well-known “thinking fast, thinking slow” phenomena. We call this the entwinement hypothesis: how latent conscious phenomena arise from the dynamics of the cognitive processing load, and how these precondition the cognitive tasks immediately following. We discuss how internal dynamical modes, which are candidates for emotions down to single qualia, can be observed by reverse engineering large sets of simulations of system’s stimulated responses, either using vast supercomputers (with full 10B neuronal network analyses) or else using laptops to do the same for appropriately generalised Kuramoto models (networks of k-dimensional clocks, each representing the 10,000 neurons within a single neural column). We explain why such simplifications are appropriate. We also discuss the consequent cognitive advantages for information-processing systems exhibiting internal sensations and the exciting implications for next-generation (non-binary) computation and for AI.
Purchase Channels and Motivation for Exercise in the Slovenian Population: Customer Behavior as a Guarantee of Fitness Center Sustainability
Authors: Vuckovic Vojko , Cuk Ivan , Duric Sasa
Published: May 2023

The sustainability of fitness centers depends on two factors: member recruitment and retention, which is why these factors have received attention in recent decades. Temporal trends in fitness center membership purchase channels from 2016 to 2022 and motivation for exercise in 2022 in the Slovenian general population were investigated. The sample included 3419 participants, including 3131 participants (age 31.03 ± 11.31 years, 1430 females) and 288 participants (age 29.39 ± 10.43 years, 110 females) for the first and second objectives, respectively. Data were assessed using a web-based recruitment questionnaire and the EMI-2 motivation questionnaire. Traditional advertising strategies such as radio and flyers are the least effective (only 0.9% of memberships in 2022), while more sophisticated advertising strategies such as the internet and social media are becoming increasingly important in the advertising world (26.6% of memberships in 2022). On the other hand, word of mouth is the most influential method, attracting 51.3% of new members. Females, older members, and Eastern Slovenians were more motivated to exercise by health and esthetic motives, and males and younger members by challenge and competition. Fitness center management should focus on providing the best possible quality of service, tailoring it to the age, gender, and motivation of customers.
Assessing the Performance of 18F-FDG PET/CT in Bladder Cancer: A Narrative Review of Current Evidence
Authors: Bacchiani Mara , Salamone Vincenzo , Massaro Eleana , Sandulli Alessandro , Mariottini Riccardo , Cadenar Anna , Di Maida Fabrizio , Pradere Benjamin , Mertens Laura , Longoni Mattia , Krajewski Wojciech , Del Giudice Francesco , D’Andrea David , Laukhtina Ekaterina , Shariat Shahrokh , Minervini Andrea , Moschini Marco , Mari Andrea ,   on behalf of European Association of Urology-Young Academic Urologists (EAU-YAU): Urothelial Carcinoma Working Group
Published: May 2023

Introduction: Lymph node (LN) involvement is a crucial determinant of prognosis for patients with bladder cancer, and an accurate staging is of utmost importance to better identify timely and appropriate therapeutic strategies. To improve the accuracy of LN detection, as an alternative to traditional methods such as CT or MRI, 18F-FDG PET/CT has been increasingly used. 18F-FDG PET/CT is also used in post-treatment restaging after neoadjuvant chemotherapy. The aim of this narrative literature review is to provide an overview of the current evidence on the use of 18F-FDG PET/CT in the diagnosis, staging, and restaging of bladder cancer, with a particular focus on its sensitivity and specificity for the detection of LN metastasis. We aim to provide clinicians with a better understanding of 18F-FDG PET/CT’s potential benefits and limitations in clinical practice. Materials and Methods: We designed a narrative review starting from a wide search in the PubMed/MEDLINE and Embase databases, selecting full-text English articles that have examined the sensibility and specificity of PET/CT for nodal staging or restaging after neoadjuvant therapy in patients with bladder cancer. The extracted data were analyzed and synthesized using a narrative synthesis approach. The results are presented in a tabular format, with a summary of the main findings of each study. Results: Twenty-three studies met the inclusion criteria: fourteen studies evaluated 18F-FDG PET/CT for nodal staging, six studies examined its accuracy for restaging after neoadjuvant therapy, and three studies evaluated both applications. To date, the use of F-18 FDG PET/TC for detection of LN metastasis in bladder cancer is controversial and uncertain: some studies showed low accuracy rates, but over the years other studies have reported evidence of high sensitivity and specificity. Conclusions: 18F-FDG PET/CT provides important incremental staging and restaging information that can potentially influence clinical management in MIBC patients. Standardization and development of a scoring system are necessary for its wider adoption. Well-designed randomized controlled trials in larger populations are necessary to provide consistent recommendations and consolidate the role of 18F-FDG PET/CT in the management of bladder cancer patients.
Primary Ovarian Leiomyosarcoma Is a Very Rare Entity: A Narrative Review of the Literature
Authors: Mandato Vincenzo Dario , Torricelli Federica , Mastrofilippo Valentina , Palicelli Andrea , Costagliola Luigi , Aguzzoli Lorenzo
Published: May 2023

Background: Primary ovarian leiomyosarcoma is a very rare malignancy characterized by unclear management and poor survival. We reviewed all the cases of primary ovarian leiomyosarcoma to identify prognostic factors and the best treatment. Methods: We collected and analyzed the articles published in the English literature regarding primary ovarian leiomyosarcoma from January 1951 to September 2022, using PubMed research. Clinical and pathological characteristics, different treatments and outcomes were analyzed. Results: 113 cases of primary ovarian leiomyosarcoma were included. Most patients received surgical resection, associated with lymphadenectomy in 12.5% of cases. About 40% of patients received chemotherapy. Follow-up information was available for 100/113 (88.5%) patients. Stage and mitotic count were confirmed to affect survival, and lymphadenectomy and chemotherapy were associated with a better survival rate. A total of 43.4% of patients relapsed, and their mean disease-free survival was 12.5 months. Conclusions: Primary ovarian leiomyosarcomas are more common in women in their 50s (mean age 53 years). Most of them are at an early stage at presentation. Advanced stage and mitotic count showed a detrimental effect on survival. Surgical excision associated with lymphadenectomy and chemotherapy are associated with increased survival. An international registry could help collect clear and reliable data to standardize the diagnosis and treatment.
Metaplastic Breast Carcinoma in U.S. Population: Racial Disparities, Survival Benefit of Adjuvant Chemoradiation and Future Personalized Treatment with Genomic Landscape
Authors: Ullah Asad , Khan Jaffar , Yasinzai Abdul Qahar Khan , Tracy Katharine , Nguyen Tena , Tareen Bisma , Garcia Andrea Agualimpia , Heneidi Saleh , Segura Sheila E.
Published: May 2023

Purpose: In this population-based study, we aim to identify factors that are influential on the survival outcome in MBC and investigate novel molecular approaches in personalized disease management. Methods: The data of this study were collected from the SEER database from 2000–2018. A total of 5315 cases were extracted from the database. The data were evaluated for demographics, tumor characteristics, metastasis, and treatment. Survival analysis was completed by using SAS software for multivariate analysis, univariate analysis, and non-parametric survival analysis. The molecular data with the most common mutations in MBC were extracted from the Catalogue of Somatic Mutations in Cancer (COSMIC) database. Results: The mean age at the time of presentation was 63.1 with a standard deviation (SD) of 14.2 years. Most patients were White (77.3%) with 15.7% Black patients, 6.1% Asian or Pacific Islander, and 0.5% American Indian. Histologically, most of the reported tumors were grade III (74.4%); 37% of the cases were triple negative (ER-, PR- and HER2-), whereas the hormone status was unknown in 46% of the cases. Spread was localized in 67.3% of patients while 26.3% had regional spread and 6.3% had distant metastases. Most tumors were unilateral (99.9%) and between 20–50 mm in size (50.6%). The lungs were the most common site for distant metastasis at diagnosis (3.42%) followed by bone (1.94%), liver (0.98%), and brain (0.56%). A combination of surgery, chemotherapy, and radiation therapy was the most common treatment with a cause-specific survival rate of 78.1% (95% CI = 75.4–80.4). The overall survival rate at 5 years was 63.6% (95% confidence interval (CI) = 62.0–65.1) with a cause-specific survival of 71.1% (95% CI = 69.5–72.6). Cause-specific survival was found to be 63.2% (95% CI = 58.9–67.1) in Black patients as compared to 72.4% (95% CI = 70.1–74.1) in White patients. Black patients also presented with higher rates of grade III disease, distant metastasis, and larger tumor size. On multivariate analysis, age > 60, grade III+, metastasis, and tumor size > 50 mm were associated with worse survival. The most common mutations in MBC identified in COSMIC data were TP53, PIK3CA, LRP1B, PTEN, and KMT2C. Conclusion: Though rare, MBC is aggressive, with poor prognosis associated with high-grade tumors, metastasis, tumor size over 50 mm, and advanced age at the time of presentation. Overall, Black women had worse clinical outcomes. MBC is difficult to treat and carries a poor prognosis that affects various races disproportionately. Continued enhancement of treatment strategies to foster more individualized care as well as continued enrollment in clinical trials are needed to improve outcomes among patients with MBC.
Actinic Keratoses: A Prospective Pilot Study on a Novel Formulation of 4% 5-Fluorouracil Cream and a Review of Other Current Topical Treatment Options
Authors: Toffoli Ludovica , Dianzani Caterina , Bonin Serena , Guarneri Claudio , Guarneri Fabrizio , Giuffrida Roberta , Zalaudek Iris , Conforti Claudio
Published: May 2023

Background: Actinic keratosis (AK) is one of the most common skin diseases, with a low risk of progression into invasive squamous cell carcinoma. We aim to assess efficacy and safety of a novel formulation of 5-Fluorouracil (5-FU) 4% with once daily application for the treatment of multiple AKs. Methods: A pilot study was performed on 30 patients with a clinical and dermoscopic diagnosis of multiple AKs, enrolled between September 2021 and May 2022 at the Dermatology Departments of two Italian hospitals. Patients were treated with 5-FU 4% cream once daily for 30 consecutive days. The Actinic Keratosis Area and Severity Index (AKASI) was calculated before starting therapy, and at each follow-up, to assess objective clinical response. Results: The cohort analyzed included 14 (47%) males and 16 (53%) females (mean age: 71 ± 12 years). A significant decrease in AKASI score at both 6 and 12 weeks (p < 0.0001) was observed. Only three patients (10%) discontinued therapy, and 13 patients (43%) did not report any adverse reactions; no unexpected adverse events were observed. Conclusions: In the setting of topical chemotherapy and immunotherapy, the new formulation of 5-FU 4% proved to be a highly effective treatment for AKs and field cancerization.
Recent Advances in Enantioselective Catalytic Electrochemical Organic Transformations
Authors: Medici Fabrizio , Resta Simonetta , Andolina Stefano , Benaglia Maurizio
Published: May 2023

Different approaches can be undertaken to realise a stereoselective electrochemical synthesis. Significant contributions to enantioselective electrochemical organic synthesis have been reported and largely reviewed in recent years. However, the development of general strategies for the electrochemical enantiocontrol of a transformation still presents considerable challenges; in particular, relatively few contributions of highly enantioselective catalytic electrochemical reactions have been reported to date. In this review article, the most recent examples of asymmetric electrochemical catalysis are discussed. The article is organised by the three types of enantioselective catalysis: metal-based catalysis, organocatalysis and biocatalysis; in each section, the most significant and recent advances are presented and discussed.
Effect of Temperature and Tapioca Flour Concentration on Manufacture of CaO·SiO2 Heterogeneous Catalyst Pellets Made from Brick Burning Ash for Biodiesel Synthesis
Authors: Iskandar Norman , Widayat Widayat , Sulardjaka Sulardjaka , Syaiful Syaiful , Fuadi Fajar , Handayani Fitri
Published: May 2023

Solid catalysts are the best choice for an effective large-scale biodiesel production process. This study aimed to analyze the characteristics of catalysts due to the influence of variations in sintering temperature and binder composition on heterogeneous catalysts of CaO·SiO2 pellets made from brick-burning residue. The catalyst was made by the sol-gel method with silica insoles with 5% KOH solvent, CaO soles with HNO3 solvent of 1.5 N, and a CaO:SiO2 ratio of 1:5. The amount of tapioca flour binders was 1%, 2%, 3%, 4%, and 5%. The resulting gel was made into a catalyst powder, sintered at various temperatures of 600 °C, 700 °C, 800 °C, 900 °C, and 1000 °C, then pelleted with a hydraulic press with a diameter of 9 mm. Catalysts were tested with density test, hardness test, PSA, XRF, XRD, and SEM. The characteristics of the CaO·SiO2 catalysts were influenced by the composition of the binding material and the sintering temperature. The test results show that the influence of variations in the composition of the binder fluctuates because the characteristics of the catalyst are also affected by the compaction process. The higher the sintering temperature, the better the catalyst will be, but if the temperature is too high it can cause agglomeration.
Fabricating Dispersed Fine Silver Nanoparticles on Liquid Substrate for Improved Photocatalytic Water Splitting Efficiency
Authors: Zhang Chuhang
Published: May 2023

Dispersed silver nanoparticles (NPs) are synthesized on a silicone oil substrate under varied substrate temperature T by thermal vaporization method. Scanning electron microscopic investigation demonstrates that the mean size of the NPs are around 7.8 nm with a standard deviation of 1.0 nm. The NPs are transferred to a strontium titanate (STO) crystal as co-catalyst for water splitting efficiency test. The photoelectrochmical (PEC) measurement reveals the photocatalytic activity of NP co-catalyst sensitively relies on T during deposition process: the relative current density jr increases from 4.8 μA/cm2 to 25.4 μA/cm2 as T goes up from 253 K to 333 K. However, a slight decrease of jr from 25.4 μA/cm2 to 22.8 μA/cm2 is found as T further increases to 353 K. The dependent behavior of jr on T is explained in term of a competition mechanism between microstructure evolution and growth model of the NPs under different T: for T ranging from 253 K to 333 K, the effect of a higher crystalline structure for NPs fabricated under higher T improves the electron transfer rate from STO to NPs is dominant. As T increases to 353 K, the overlapping of NPs become a factor for photocatalytic activity of NP/STO system: the diffusion distance of electrons becomes larger and the apparent contact area between NPs and STO is reduced which in turn reduce the photocatalytic activity of NP/STO. The experimental method to synthesize NPs in this report may open up a way to further apply fine NPs in enhancing photocatalytic water splitting efficiency.
Intracellular Angiotensin II Stimulation of Sodium Transporter Expression in Proximal Tubule Cells via AT1 (AT1a) Receptor-Mediated, MAP Kinases ERK1/2- and NF-кB-Dependent Signaling Pathways
Authors: Li Xiaochun , Zhuo Jialong
Published: May 2023

The current prevailing paradigm in the renin-angiotensin system dictates that most, if not all, biological, physiological, and pathological responses to its most potent peptide, angiotensin II (Ang II), are mediated by extracellular Ang II activating its cell surface receptors. Whether intracellular (or intracrine) Ang II and its receptors are involved remains incompletely understood. The present study tested the hypothesis that extracellular Ang II is taken up by the proximal tubules of the kidney by an AT1 (AT1a) receptor-dependent mechanism and that overexpression of an intracellular Ang II fusion protein (ECFP/Ang II) in mouse proximal tubule cells (mPTC) stimulates the expression of Na+/H+ exchanger 3 (NHE3), Na+/HCO3- cotransporter, and sodium and glucose cotransporter 2 (Sglt2) by AT1a/MAPK/ERK1/2/NF-kB signaling pathways. mPCT cells derived from male wild-type and type 1a Ang II receptor-deficient mice (Agtr1a-/-) were transfected with an intracellular enhanced cyan fluorescent protein-tagged Ang II fusion protein, ECFP/Ang II, and treated without or with AT1 receptor blocker losartan, AT2 receptor blocker PD123319, MEK1/MEK2 inhibitor U0126, NF-кB inhibitor RO 106-9920, or p38 MAP kinase inhibitor SB202196, respectively. In wild-type mPCT cells, the expression of ECFP/Ang II significantly increased NHE3, Na+/HCO3-, and Sglt2 expression (p < 0.01). These responses were accompanied by >3-fold increases in the expression of phospho-ERK1/2 and the p65 subunit of NF-кB (p < 0.01). Losartan, U0126, or RO 106-9920 all significantly attenuated ECFP/Ang II-induced NHE3 and Na+/HCO3- expression (p < 0.01). Deletion of AT1 (AT1a) receptors in mPCT cells attenuated ECFP/Ang II-induced NHE3 and Na+/HCO3- expression (p < 0.01). Interestingly, the AT2 receptor blocker PD123319 also attenuated ECFP/Ang II-induced NHE3 and Na+/HCO3- expression (p < 0.01). These results suggest that, similar to extracellular Ang II, intracellular Ang II may also play an important role in Ang II receptor-mediated proximal tubule NHE3, Na+/HCO3-, and Sglt2 expression by activation of AT1a/MAPK/ERK1/2/NF-kB signaling pathways.
IRF3 Activation in Mast Cells Promotes FcεRI-Mediated Allergic Inflammation
Authors: Choi Young-Ae , Dhakal Hima , Lee Soyoung , Kim Namkyung , Lee Byungheon , Kwon Taeg Kyu , Khang Dongwoo , Kim Sang-Hyun
Published: May 2023

(1) Background: This study aims to elucidate a novel non-transcriptional action of IRF3 in addition to its role as a transcription factor in mast cell activation and associated allergic inflammation; (2) Methods: For in vitro experiments, mouse bone-marrow-derived mast cells (mBMMCs) and a rat basophilic leukemia cell line (RBL-2H3) were used for investigating the underlying mechanism of IRF3 in mast-cell-mediated allergic inflammation. For in vivo experiments, wild-type and Irf3 knockout mice were used for evaluating IgE-mediated local and systemic anaphylaxis; (3) Results: Passive cutaneous anaphylaxis (PCA)-induced tissues showed highly increased IRF3 activity. In addition, the activation of IRF3 was observed in DNP-HSA-treated mast cells. Phosphorylated IRF3 by DNP-HSA was spatially co-localized with tryptase according to the mast cell activation process, and FcεRI-mediated signaling pathways directly regulated that activity. The alteration of IRF3 affected the production of granule contents in the mast cells and the anaphylaxis responses, including PCA- and ovalbumin-induced active systemic anaphylaxis. Furthermore, IRF3 influenced the post-translational processing of histidine decarboxylase (HDC), which is required for granule maturation; and (4) Conclusion: Through this study, we demonstrated the novel function of IRF3 as an important factor inducing mast cell activation and as an upstream molecule for HDC activity.
Agricultural Biomass Waste to Biochar: A Review on Biochar Applications Using Machine Learning Approach and Circular Economy
Authors: Rex Prathiba , Mohammed Ismail Kalil , Meenakshisundaram Nagaraj , Barmavatu Praveen , Sai Bharadwaj A
Published: May 2023

Biochar has gained attention as an alternative source of solid energy and for the proper disposal of agricultural biomass waste (ABW). Microwave-assisted pyrolysis (MAP) is a promising approach for the production of biochar. This review article presents the beneficial use of biochar for soil fertilization, machine learning (ML), the circular bioeconomy, and the technology readiness level. The use of machine learning techniques helps to design, predict, and optimize the process. It can also improve the accuracy and efficacy of the biochar production process, thereby reducing costs. Furthermore, the use of biochar as a soil amendment can be an attractive option for farmers. The incorporation of biochar into soil has been shown to improve soil fertility, water retention, and crop productivity. This can lead to reduced dependence on synthetic fertilizers and increased agricultural yields. The development of a biochar economy has the potential to create new job opportunities and increase the national gross domestic product (GDP). Small-scale enterprises can play a significant role in the production and distribution of biochar, providing value-added products and helping to promote sustainable agriculture.
The Importance of Implementing a Transition Strategy for Patients with Muscular Dystrophy: From Child to Adult—Insights from a Tertiary Centre for Rare Neurological Diseases
Authors: Lupu Maria , Ioghen Mihaela , Perjoc Radu-Ștefan , Scarlat Andra-Maria , Vladâcenco Oana Aurelia , Roza Eugenia , Epure Diana Ana-Maria , Teleanu Raluca Ioana , Severin Emilia Maria
Published: May 2023

Progress in the field of muscular dystrophy (MD) using a multidisciplinary approach based on international standards of care has led to a significant increase in the life expectancy of patients. The challenge of transitioning from pediatric to adult healthcare has been acknowledged for over a decade, yet it continues to be a last-minute concern. Currently, there is no established consensus on how to evaluate the effectiveness of the transition process. Our study aimed to identify how well patients are prepared for the transition and to determine their needs. We conducted a descriptive, cross-sectional study on 15 patients aged 14 to 21 years. The patients completed a sociodemographic and a Transition Readiness Assessment Questionnaire (TRAQ). We also analyzed the comorbidities of these patients. Our study revealed that only 46.7% of the patients had engaged in a conversation with a medical professional, namely, a child neurologist, about transitioning. A total of 60% of the participants expressed having confidence in their self-care ability. However, the median TRAQ score of 3.6 shows that these patients overestimate themselves. We emphasize the necessity for a slow, personalized transition led by a multidisciplinary team to ensure the continuity of state-of-the-art care from pediatric to adult healthcare services and the achievement of the highest possible quality of life for these patients.
Digital Devices Use and Fine Motor Skills in Children between 3–6 Years
Authors: Operto Francesca Felicia , Viggiano Andrea , Perfetto Antonio , Citro Gabriella , Olivieri Miriam , Simone Valeria de , Bonuccelli Alice , Orsini Alessandro , Aiello Salvatore , Coppola Giangennaro , Pastorino Grazia Maria Giovanna
Published: May 2023

(1) Background: The principal aim of our research was to explore the relationship between digital devices use and fine motor skills in children aged three to six years and to explore the effect of some socio-demographic factors. (2) Methods: we enrolled 185 children aged between three to six years. The parents of all the participants fulfilled a questionnaire to explore the digital device use, and their children performed a standardized test to assess fine motor skills (APCM-2). We performed the Spearman correlation test to explore the relationship between different variables. (3) Results: the children spent an average of 3.08 ± 2.30 h/day on digital devices. We did not find a significant association between the time of use of digital devices and fine motor skills (p = 0.640; r = −0.036). The youngest children experienced digital tools earlier than older ones (p < 0.001; r = 0.424) and they were also the ones who used digital tools more time afterwards (p = 0.012; −0.202). The children who had working parents spent more time on digital devices (p = 0.028; r = 0.164/p = 0.037; r = 0.154) and used digital devices earlier (p = 0.023; r = 0.171). (4) Conclusions: This data suggest that it would be useful to monitor the use of digital tools, especially in the very first years of life. Future studies are needed to further explore this topic.