bluuebunny/crossref_metadata_2025 huggingface dataset:
The Janus-Faced Role of Lipid Droplets in Aging: Insights from the Cellular Perspective
Authors: Bresgen Nikolaus , Kovacs Melanie , Lahnsteiner Angelika , Felder Thomas Klaus , Rinnerthaler Mark
Published: May 2023

It is widely accepted that nine hallmarks—including mitochondrial dysfunction, epigenetic alterations, and loss of proteostasis—exist that describe the cellular aging process. Adding to this, a well-described cell organelle in the metabolic context, namely, lipid droplets, also accumulates with increasing age, which can be regarded as a further aging-associated process. Independently of their essential role as fat stores, lipid droplets are also able to control cell integrity by mitigating lipotoxic and proteotoxic insults. As we will show in this review, numerous longevity interventions (such as mTOR inhibition) also lead to strong accumulation of lipid droplets in Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, and mammalian cells, just to name a few examples. In mammals, due to the variety of different cell types and tissues, the role of lipid droplets during the aging process is much more complex. Using selected diseases associated with aging, such as Alzheimer’s disease, Parkinson’s disease, type II diabetes, and cardiovascular disease, we show that lipid droplets are “Janus”-faced. In an early phase of the disease, lipid droplets mitigate the toxicity of lipid peroxidation and protein aggregates, but in a later phase of the disease, a strong accumulation of lipid droplets can cause problems for cells and tissues.
Application of Inositol Hexaphosphate and Inositol in Dental Medicine: An Overview
Authors: Druzijanic Ana , Kovic Mare , Roguljic Marija , Cigic Livia , Majstorovic Martina , Vucenik Ivana
Published: May 2023

Phosphorylated inositol hexaphosphate (IP6) is a naturally occurring carbohydrate, and its parent compound, myoinositol (Ins), is abundantly present in plants, particularly in certain high-fiber diets, but also in mammalian cells, where they regulate essential cellular functions. IP6 has profound modulation effects on macrophages, which warrants further research on the therapeutic benefits of IP6 for inflammatory diseases. Here, we review IP6 as a promising compound that has the potential to be used in various areas of dentistry, including endodontics, restorative dentistry, implantology, and oral hygiene products, due to its unique structure and characteristic properties. Available as a dietary supplement, IP6 + Ins has been shown to enhance the anti-inflammatory effect associated with preventing and suppressing the progression of chronic dental inflammatory diseases. IP6 in dentistry is now substantial, and this narrative review presents and discusses the different applications proposed in the literature and gives insights into future use of IP6 in the fields of orthodontics, periodontics, implants, and pediatric dentistry.
Serum Urotensin II Levels Are Elevated in Patients with Obstructive Sleep Apnea
Authors: Mihovilovic Ante , Dogas Zoran , Martinovic Dinko , Tokic Daria , Puizina Mladinic Ema , Kumric Marko , Ivkovic Natalija , Vilovic Marino , Bozic Josko
Published: May 2023

Obstructive sleep apnea (OSA) has become major public concern and is continuously investigated in new aspects of pathophysiology and management. Urotensin II (UII) is a powerful vasoconstrictor with a role in cardiovascular diseases. The main goal of this study was to evaluate serum UII levels in OSA patients and matched controls. A total of 89 OSA patients and 89 controls were consecutively enrolled. A medical history review and physical examination of the participants was conducted, with polysomnography performed in the investigated group. UII levels and other biochemical parameters were assessed according to the standard laboratory protocols. The median AHI in the OSA group was 39.0 (31.4–55.2) events/h, and they had higher levels of hsCRP when compared to control group (2.87 ± 0.71 vs. 1.52 ± 0.68 mg/L; p < 0.001). Additionally, serum UII levels were significantly higher in the OSA group (3.41 ± 1.72 vs. 2.18 ± 1.36 ng/mL; p < 0.001), while positive correlation was found between UII levels and hsCRP (r = 0.450; p < 0.001) and systolic blood pressure (SPB) (r = 0.317; p < 0.001). Finally, multiple regression analysis showed significant association of UII levels with AHI (0.017 ± 0.006, p = 0.013), SBP (0.052 ± 0.008, p < 0.001) and hsCRP (0.538 ± 0.164, p = 0.001). As UII levels were associated with blood pressure and markers of inflammation and OSA severity, it might play an important role in the complex pathophysiology of OSA and its cardiometabolic complications.
Activation Mechanisms and Diverse Functions of Mammalian Phospholipase C
Authors: Kanemaru Kaori , Nakamura Yoshikazu
Published: May 2023

Phospholipase C (PLC) plays pivotal roles in regulating various cellular functions by metabolizing phosphatidylinositol 4,5-bisphosphate in the plasma membrane. This process generates two second messengers, inositol 1,4,5-trisphosphate and diacylglycerol, which respectively regulate the intracellular Ca2+ levels and protein kinase C activation. In mammals, six classes of typical PLC have been identified and classified based on their structure and activation mechanisms. They all share X and Y domains, which are responsible for enzymatic activity, as well as subtype-specific domains. Furthermore, in addition to typical PLC, atypical PLC with unique structures solely harboring an X domain has been recently discovered. Collectively, seven classes and 16 isozymes of mammalian PLC are known to date. Dysregulation of PLC activity has been implicated in several pathophysiological conditions, including cancer, cardiovascular diseases, and neurological disorders. Therefore, identification of new drug targets that can selectively modulate PLC activity is important. The present review focuses on the structures, activation mechanisms, and physiological functions of mammalian PLC.
Lipidomics Profiling and Risk of Coronary Artery Disease in the BioHEART-CT Discovery Cohort
Authors: Zhu Dantong , Vernon Stephen T. , D’Agostino Zac , Wu Jingqin , Giles Corey , Chan Adam S. , Kott Katharine A. , Gray Michael P. , Gholipour Alireza , Tang Owen , Beyene Habtamu B. , Patrick Ellis , Grieve Stuart M. , Meikle Peter J. , Figtree Gemma A. , Yang Jean Y. H.
Published: May 2023

The current coronary artery disease (CAD) risk scores for predicting future cardiovascular events rely on well-recognized traditional cardiovascular risk factors derived from a population level but often fail individuals, with up to 25% of first-time heart attack patients having no risk factors. Non-invasive imaging technology can directly measure coronary artery plaque burden. With an advanced lipidomic measurement methodology, for the first time, we aim to identify lipidomic biomarkers to enable intervention before cardiovascular events. With 994 participants from BioHEART-CT Discovery Cohort, we collected clinical data and performed high-performance liquid chromatography with mass spectrometry to determine concentrations of 683 plasma lipid species. Statin-naive participants were selected based on subclinical CAD (sCAD) categories as the analytical cohort (n = 580), with sCAD+ (n = 243) compared to sCAD− (n = 337). Through a machine learning approach, we built a lipid risk score (LRS) and compared the performance of the existing Framingham Risk Score (FRS) in predicting sCAD+. We obtained individual classifiability scores and determined Body Mass Index (BMI) as the modifying variable. FRS and LRS models achieved similar areas under the receiver operating characteristic curve (AUC) in predicting the validation cohort. LRS enhanced the prediction of sCAD+ in the healthy-weight group (BMI < 25 kg/m2), where FRS performed poorly and identified individuals at risk that FRS missed. Lipid features have strong potential as biomarkers to predict CAD plaque burden and can identify residual risk not captured by traditional risk factors/scores. LRS compliments FRS in prediction and has the most significant benefit in healthy-weight individuals.
Public Health Needs the Public Trust: A Pandemic Retrospective
Authors: Halma Matthew T. J. , Guetzkow Joshua
Published: May 2023

The COVID crisis of the past three years has greatly impacted stakeholder relationships between scientists, health providers, policy makers, pharmaceutical industry employees, and the public. Lockdowns and restrictions of civil liberties strained an already fraught relationship between the public and policy makers, with scientists also seen as complicit in providing the justification for the abrogation of civil liberties. This was compounded by the suppression of open debate over contentious topics of public interest and a violation of core bioethical principles embodied in the Nuremberg Code. Overall, the policies chosen during the pandemic have had a corrosive impact on public trust, which is observable in surveys and consumer behaviour. While a loss of trust is difficult to remedy, the antidotes are accountability and transparency. This narrative review presents an overview of key issues that have motivated public distrust during the pandemic and ends with suggested remedies. Scientific norms and accountability must be restored in order to rebuild the vital relationship between scientists and the public they serve.
Role of Melatonin in the Onset of Metabolic Syndrome in Women
Authors: Peneva Vania Miloucheva , Terzieva Dora Dimitrova , Mitkov Mitko Dimitrov
Published: May 2023

Metabolic syndrome (MetS) is a constellation of several associated cardiometabolic risk factors that increase the risk of developing type 2 diabetes mellitus (T2DM), cardiovascular diseases, and mortality. The role of hormonal factors in the development of MetS is assumed. In women, an insulin-resistant state that is associated with polycystic ovarian syndrome and increased deposition of intra-abdominal adipose tissue promotes the development of MetS and increases cardiovascular risk. The neuroendocrine hormone melatonin is secreted mainly at night under the regulatory action of the suprachiasmatic nucleus in the hypothalamus. Melatonin secretion is influenced by exogenous factors such as light and seasons and endogenous factors such as age, sex, and body weight. At present, the role of melatonin in metabolic disorders in humans is not fully understood. In this review, we set out to analyze the relationship of melatonin with the main features of MetS in women. Data from experimental and clinical studies on the role of melatonin in glucose metabolism and on the involvement of melatonin in lipid disturbances in MetS are reviewed. The complex influence of melatonin on hypertension is discussed. The changes in melatonin, leptin, and ghrelin and their relation to various metabolic processes and vascular dysfunction are discussed.
COVID-19 Vaccines and Atrial Fibrillation: Analysis of the Post-Marketing Pharmacovigilance European Database
Authors: Ruggiero Rosanna , Donniacuo Maria , Mascolo Annamaria , Gaio Mario , Cappetta Donato , Rafaniello Concetta , Docimo Giovanni , Riccardi Consiglia , Izzo Imma , Ruggiero Donatella , Paolisso Giuseppe , Rossi Francesco , De Angelis Antonella , Capuano Annalisa
Published: May 2023

Atrial fibrillation (AF) has been described in COVID-19 patients. Recently, some case reports and US pharmacovigilance analyses described AF onset as a rare adverse event following COVID-19 vaccination. The possible correlation is unclear. We systematically analyzed the reports of AF related to COVID-19 vaccines collected in the European pharmacovigilance database, EudraVigilance (EV), from 2020 to November 2022. We carried out descriptive and disproportionality analyses. Moreover, we performed a sensitivity analysis, excluding the reports describing other possible alternative AF causes (pericarditis, myocarditis, COVID-19, or other drugs that may cause/exacerbate AF). Overall, we retrieved 6226 reports, which represented only 0.3% of all those related to COVID-19 vaccines collected in EV during our study period. AF reports mainly referred to adults (in particular, >65 years old), with an equal distribution in sex. Reports were mainly related to tozinameran (54.04%), elasomeran (28.3%), and ChAdOx1-S (14.32%). The reported AF required patient hospitalization in 35% of cases and resulted in a life-threatening condition in 10% of cases. The AF duration (when reported) was highly variable, but the majority of the events had a short duration (moda = 24 h). Although an increased frequency of AF reporting with mRNA vaccines emerges from our study, other investigations are required to investigate the possible correlation between COVID-19 vaccination and the rare AF occurrence.
Effects of Whole-Body Cryostimulation on Pain Management and Disease Activity in Active Rheumatic Polymyalgia: A Case-Report
Authors: Verme Federica , Scarpa Alessandra , Varallo Giorgia , Piterà Paolo , Capodaglio Paolo , Fontana Jacopo Maria
Published: May 2023

Polymyalgia rheumatica (PMR) is the most common inflammatory rheumatic disease among people over 50 and occurs with symptoms such as musculoskeletal pain and stiffness in the neck, shoulders, and hips. To date, corticosteroids represent the cornerstone of PMR treatment. However, it is well known that their prolonged use is associated with several adverse effects, making it crucial to find therapeutic alternatives. The purpose of this case report was to describe the effectiveness of 10 whole-body cryostimulation (WBC) sessions on a 74-year-old woman suffering from PMR. An improvement in disease impact, fatigue, pain, quality of sleep, and total physical activity was observed after WBC. Moreover, the patient reduced her daily drug intake by 67% following WBC treatments. Given the increasing prevalence of PMR and considering the side effects that drug treatments can lead to, WBC could represent a valuable adjuvant and well-tolerated alternative for treating PMR.
Probabilistic Incremental Dynamic Analysis for Seismic Isolation Systems through Integration with the NHERI-SimCenter Performance-Based Engineering Application
Authors: AlHamaydeh Mohammad , Maky Ahmed , ElKafrawy Mohamed
Published: May 2023

In the wake of the 1994 Northridge and 1995 Kobe earthquakes, structural designers adopted performance-based engineering concepts instead of traditional deterministic design approaches. The primary change was to evaluate the design according to stakeholders’ interests instead of the engineering parameters. This evaluation process required a probabilistic estimation for the included variables at all design stages. The NHERI-SimCenter application framework provides generic solutions implemented in different hazard simulation problems. Seismic isolation is an efficient, proven technique for improving seismic performance by limiting drift ratios and reducing damage. During the design stage, seismic isolation-system parameters must be carefully calibrated to control different aspects of the response, and it is necessary to run multiple simulations and count for parameter uncertainties. This research introduced components for seismic isolation and incremental dynamic analysis procedures integrated with framework modules, such as uncertainty quantifications and damage and loss estimation. Furthermore, an illustrative case study was included to reflect the impacts of this development.
Extracellular Vesicles and Epidermal Growth Factor Receptor Activation: Interplay of Drivers in Cancer Progression
Authors: Ferlizza Enea , Romaniello Donatella , Borrelli Francesco , Pagano Federica , Girone Cinzia , Gelfo Valerio , Kuhre Rikke Sofie , Morselli Alessandra , Mazzeschi Martina , Sgarzi Michela , Filippini Daria Maria , D’Uva Gabriele , Lauriola Mattia
Published: May 2023

Extracellular vesicles (EVs) are of great interest to study the cellular mechanisms of cancer development and to diagnose and monitor cancer progression. EVs are a highly heterogeneous population of cell derived particles, which include microvesicles (MVs) and exosomes (EXOs). EVs deliver intercellular messages transferring proteins, lipids, nucleic acids, and metabolites with implications for tumour progression, invasiveness, and metastasis. Epidermal Growth Factor Receptor (EGFR) is a major driver of cancer. Tumour cells with activated EGFR could produce EVs disseminating EGFR itself or its ligands. This review provides an overview of EVs (mainly EXOs and MVs) and their cargo, with a subsequent focus on their production and effects related to EGFR activation. In particular, in vitro studies performed in EGFR-dependent solid tumours and/or cell cultures will be explored, thus shedding light on the interplay between EGFR and EVs production in promoting cancer progression, metastases, and resistance to therapies. Finally, an overview of liquid biopsy approaches involving EGFR and EVs in the blood/plasma of EGFR-dependent tumour patients will also be discussed to evaluate their possible application as candidate biomarkers.
Co-Creation of Breast Cancer Risk Communication Tools and an Assessment of Risk Factor Awareness: A Qualitative Study of Patients and the Public in India
Authors: Pillai Divya , Narayan Jyoti , Gentry-Maharaj Aleksandra , Deo Suryanarayana , Vijaykumar Dehannathparambil Kottarathil , Mukherjee Poulome , Wadhwa Nitya , Bhasin Aparajita , Mishra Ashutosh , Rajanbabu Anupama , Kannan Ravi , Husain Zakir , Kumar Avinash , Antoniou Antonis C. , Manchanda Ranjit , Menon Usha
Published: May 2023

Background: Low awareness of BC and its associated risk factors causes delays in diagnosis and impacts survival. It is critical to communicate BC risk to patients in a format that they are easily able to understand. Our study aim was to develop easy-to-follow transmedia prototypes to communicate BC risk and evaluate user preferences, alongside exploring awareness of BC and its risk factors. Methods: Prototypes of transmedia tools for risk communication were developed with multidisciplinary input. A qualitative in-depth online interview study was undertaken using a pre-defined topic guide of BC patients (7), their relatives (6), the general public (6), and health professionals (6). Interviews were analyzed using a thematic approach. Findings: Most participants preferred pictographic representations (frequency format) of lifetime risk and risk factors and storytelling using short animations and comic strips (infographics) for communicating genetic risk and testing: “In a short time, they explained it very well, and I liked it”. Suggestions included minimizing technical terminology, decreasing the delivery speed, “two-way dialogue”, and using local “language for different locations”. There was low awareness of BC, with some understanding of age and hereditary risk factors but limited knowledge of reproductive factors. Interpretation: Our findings support use of multiple context-specific multimedia tools in communicating cancer risk in an easy-to-understand way. The preference for storytelling using animations and infographics is a novel finding and should be more widely explored.
Natural Products for the Prevention, Treatment and Progression of Breast Cancer
Authors: Svolacchia Fabiano , Brongo Sergio , Catalano Alessia , Ceccarini Agostino , Svolacchia Lorenzo , Santarsiere Alessandro , Scieuzo Carmen , Salvia Rosanna , Finelli Francesca , Milella Luigi , Saturnino Carmela , Sinicropi Maria Stefania , Fabrizio Tommaso , Giuzio Federica
Published: May 2023

In this review, we summarize the most used natural products as useful adjuvants in BC by clarifying how these products may play a critical role in the prevention, treatment and progression of this disease. BC is the leading cancer, in terms of incidence, that affects women. The epidemiology and pathophysiology of BC were widely reported. Inflammation and cancer are known to influence each other in several tumors. In the case of BC, the inflammatory component precedes the development of the neoplasm through a slowly increasing and prolonged inflammation that also favors its growth. BC therapy involves a multidisciplinary approach comprising surgery, radiotherapy and chemotherapy. There are numerous observations that showed that the effects of some natural substances, which, in integration with the classic protocols, can be used not only for prevention or integration in order to prevent recurrences and induce a state of chemoquiescence but also as chemo- and radiosensitizers during classic therapy.
Matrix Metalloproteinase 9 Induced in Esophageal Squamous Cell Carcinoma Cells via Close Contact with Tumor-Associated Macrophages Contributes to Cancer Progression and Poor Prognosis
Authors: Tsukamoto Shuichi , Koma Yu-ichiro , Kitamura Yu , Tanigawa Kohei , Azumi Yuki , Miyako Shoji , Urakami Satoshi , Hosono Masayoshi , Kodama Takayuki , Nishio Mari , Shigeoka Manabu , Yokozaki Hiroshi
Published: May 2023

Tumor-associated macrophages (TAMs) contribute to disease progression in various cancers, including esophageal squamous cell carcinoma (ESCC). We have previously used an indirect co-culture system between ESCC cell lines and macrophages to analyze their interactions. Recently, we established a direct co-culture system to closely simulate actual ESCC cell-TAM contact. We found that matrix metalloproteinase 9 (MMP9) was induced in ESCC cells by direct co-culture with TAMs, not by indirect co-culture. MMP9 was associated with ESCC cell migration and invasion, and its expression was controlled by the Stat3 signaling pathway in vitro. Immunohistochemical analyses revealed that MMP9 expression in cancer cells at the invasive front (“cancer cell MMP9”) was related to high infiltration of CD204 positive M2-like TAMs (p < 0.001) and was associated with worse overall and disease-free survival of patients (p = 0.036 and p = 0.038, respectively). Furthermore, cancer cell MMP9 was an independent prognostic factor for disease-free survival. Notably, MMP9 expression in cancer stroma was not associated with any clinicopathological factors or patient prognoses. Our results suggest that close interaction with TAMs infiltrating in cancer stroma or cancer nests induces MMP9 expression in ESCC cells, equipping them with more malignant features.
How ITD Insertion Sites Orchestrate the Biology and Disease of FLT3-ITD-Mutated Acute Myeloid Leukemia
Authors: Haage Tobias R. , Schraven Burkhart , Mougiakakos Dimitrios , Fischer Thomas
Published: May 2023

Mutations of the FLT3 gene are among the most common genetic aberrations detected in AML and occur mainly as internal tandem duplications (FLT3-ITD). However, the specific sites of FLT3-ITD insertion within FLT3 show marked heterogeneity regarding both biological and clinical features. In contrast to the common assumption that ITD insertion sites (IS) are restricted to the juxtamembrane domain (JMD) of FLT3, 30% of FLT3-ITD mutations insert at the non-JMD level, thereby integrating into various segments of the tyrosine kinase subdomain 1 (TKD1). ITDs inserted within TKD1 have been shown to be associated with inferior complete remission rates as well as shorter relapse-free and overall survival. Furthermore, resistance to chemotherapy and tyrosine kinase inhibition (TKI) is linked to non-JMD IS. Although FLT3-ITD mutations in general are already recognized as a negative prognostic marker in currently used risk stratification guidelines, the even worse prognostic impact of non-JMD-inserting FLT3-ITD has not yet been particularly considered. Recently, the molecular and biological assessment of TKI resistance highlighted the pivotal role of activated WEE1 kinase in non-JMD-inserting ITDs. Overcoming therapy resistance in non-JMD FLT3-ITD-mutated AML may lead to more effective genotype- and patient-specific treatment approaches.
Immunotherapy through the Lens of Non-Small Cell Lung Cancer
Authors: Stanley Robyn , Flanagan Saoirse , Reilly David O’ , Kearney Ella , Naidoo Jarushka , Dowling Catríona M.
Published: May 2023

Immunotherapy has revolutionised anti-cancer treatment in solid organ malignancies. Specifically, the discovery of CTLA-4 followed by PD-1 in the early 2000s led to the practice-changing clinical development of immune checkpoint inhibitors (ICI). Patients with lung cancer, including both small cell (SCLC) and non-small cell lung cancer (NSCLC), benefit from the most commonly used form of immunotherapy in immune checkpoint inhibitors (ICI), resulting in increased survival and quality of life. In NSCLC, the benefit of ICIs has now extended from advanced NSCLC to earlier stages of disease, resulting in durable benefits and the even the emergence of the word ‘cure’ in long term responders. However, not all patients respond to immunotherapy, and few patients achieve long-term survival. Patients may also develop immune-related toxicity, a small percentage of which is associated with significant mortality and morbidity. This review article highlights the various types of immunotherapeutic strategies, their modes of action, and the practice-changing clinical trials that have led to the widespread use of immunotherapy, with a focus on ICIs in NSCLC and the current challenges associated with advancing the field of immunotherapy.
The Impact of NAD Bioavailability on DNA Double-Strand Break Repair Capacity in Human Dermal Fibroblasts after Ionizing Radiation
Authors: Svetlova Maria , Solovjeva Ljudmila , Kropotov Andrey , Nikiforov Andrey
Published: May 2023

Nicotinamide adenine dinucleotide (NAD) serves as a substrate for protein deacetylases sirtuins and poly(ADP-ribose) polymerases, which are involved in the regulation of DNA double-strand break (DSB) repair molecular machinery by various mechanisms. However, the impact of NAD bioavailability on DSB repair remains poorly characterized. Herein, using immunocytochemical analysis of γH2AX, a marker for DSB, we investigated the effect of the pharmacological modulation of NAD levels on DSB repair capacity in human dermal fibroblasts exposed to moderate doses of ionizing radiation (IR). We demonstrated that NAD boosting with nicotinamide riboside did not affect the efficiency of DSB elimination after the exposure of cells to IR at 1 Gy. Moreover, even after irradiation at 5 Gy, we did not observe any decrease in intracellular NAD content. We also showed that, when the NAD pool was almost completely depleted by inhibition of its biosynthesis from nicotinamide, cells were still able to eliminate IR-induced DSB, though the activation of ATM kinase, its colocalization with γH2AX and DSB repair capacity were reduced in comparison to cells with normal NAD levels. Our results suggest that NAD-dependent processes, such as protein deacetylation and ADP-ribosylation, are important but not indispensable for DSB repair induced by moderate doses of IR.
Large-Scale Production of Anti-RNase A VHH Expressed in pyrG Auxotrophic Aspergillus oryzae
Authors: Karaman Elif , Eyüpoğlu Alp Ertunga , Mahmoudi Azar Lena , Uysal Serdar
Published: May 2023

Nanobodies, also referred to as VHH antibodies, are the smallest fragments of naturally produced camelid antibodies and are ideal affinity reagents due to their remarkable properties. They are considered an alternative to monoclonal antibodies (mAbs) with potential utility in imaging, diagnostic, and other biotechnological applications given the difficulties associated with mAb expression. Aspergillus oryzae (A. oryzae) is a potential system for the large-scale expression and production of functional VHH antibodies that can be used to meet the demand for affinity reagents. In this study, anti-RNase A VHH was expressed under the control of the glucoamylase promoter in pyrG auxotrophic A. oryzae grown in a fermenter. The feature of pyrG auxotrophy, selected for the construction of a stable and efficient platform, was established using homologous recombination. Pull-down assay, size exclusion chromatography, and surface plasmon resonance were used to confirm the binding specificity of anti-RNase A VHH to RNase A. The affinity of anti-RNase A VHH was nearly 18.3-fold higher (1.9 nM) when expressed in pyrG auxotrophic A. oryzae rather than in Escherichia coli. This demonstrates that pyrG auxotrophic A. oryzae is a practical, industrially scalable, and promising biotechnological platform for the large-scale production of functional VHH antibodies with high binding activity.
Influence of Wet Film Thickness on the Functional Applications of Biopolymers in Paper Conservation
Authors: Aleksić Gabriela , Cigula Tomislav , Vukoje Marina , Itrić Ivanda Katarina
Published: May 2023

In heritage conservation, paper deterioration can be slowed down by controlling the environmental conditions surrounding heritage objects and stabilizing the materials these objects are made of. As conservation materials can also cause optical, chemical, and physical changes in the object, their application should be safe, minimalistic, and purposeful. This paper aimed to observe the functional applications of three biopolymers used in paper conservation. For that purpose, a model paper was coated with methylcellulose (MC), cellulose nanocrystals (CNCs), and wheat starch (WSP) using different wet film deposits. The prepared samples were characterized by determining their physical, optical, and surface properties. The results show that changes in the wet film deposit thickness influenced paper properties. With CNCs, the increase has caused a drastic change of colour properties, with MC hydrophobicity increased and with WSP grammage and thickness increased. All coatings (except CNC24) have contributed to the preservation of the colour properties of the paper from the damage caused by thermal ageing.
Buckling Analysis of Laminated Stiffened Plates with Material Anisotropy Using the Rayleigh–Ritz Approach
Authors: Stamatelos Dimitrios G. , Labeas George N.
Published: May 2023

An energy-based solution for calculating the buckling loads of partially anisotropic stiffened plates is presented, such as antisymmetric cross-ply and angle-ply laminations. A discrete approach, for the mathematical modelling and formulations of the stiffened plates, is followed. The developed formulations extend the Rayleigh–Ritz method and explore the available anisotropic unstiffened plate buckling solutions to the interesting cases of stiffened plates with some degree of material anisotropy. The examined cases consider simply supported unstiffened and stiffened plates under uniform and linearly varying compressive loading. Additionally, a reference finite element (FE) model is developed to compare the calculated buckling loads and validate the modelling approach for its accuracy. The results of the developed method are also compared with the respective experimental results for the cases where they were available in the literature. Finally, an extended discussion regarding the assumptions and restrictions of the applied Rayleigh–Ritz method is made, so that the limitations of the developed method are identified and documented.
Microwave Dielectric Properties of Li3TiO3F Oxyfluorides Ceramics
Authors: Yao Guoguang , Zhao Jiuyan , Lu Ya , Liu Hongkai , Pei Cuijin , Ding Qian , Chen Miao , Zhang Yaming , Li Ding , Wang Fu
Published: May 2023

Using a solid-state reaction strategy, nominal Li3TiO3F oxyfluorides ceramics were fabricated, and its sintering behavior, microstructure, phase assemblages, as well as microwave dielectric performances were all investigated. The main phase of Li3TiO3F with cubic structures accompanied with small amounts of the LiF or Li2TiO3 secondary phase was identified by XRD analysis. SEM analysis showed that a uniform and dense microstructure was obtained for 750 °C-sintered samples. The dielectric constant (εr) and quality factor (Q × f) were found to be strongly correlated with porosity and grain size distribution, whereas the temperature coefficient of resonance frequency (τf) was mainly dominated by the phase assemblages. In particular, the 750 °C-sintered Li3TiO3F samples exhibited good microwave dielectric performances: εr = 18, Q × f = 57,300 GHz (under 9.2 GHz), τf = −43.0 ppm/°C.
Effect of Blend-Pelleted Products Based on Carinata Meal or Canola Meal in Combination with Lignosulfonate on Ruminal Degradation and Fermentation Characteristics, Intestinal Digestion, and Feed Milk Value When Fed to Dairy Cows
Authors: Ismael Aya , Refat Basim , Guevara-Oquendo Victor Hugo , Yu Peiqiang
Published: May 2023

The objectives of this study were to investigate the effect of newly developed blend-pelleted products based on carinata meal (BPPCR) or canola meal (BPPCN) in combination with peas and lignosulfonate on ruminal fermentation characteristics, degradation kinetics, intestinal digestion and feed milk values (FMV) when fed to high-producing dairy cows. Three dietary treatments were Control = control diet (common barley-based diet in western Canada); BPPCR = basal diet supplemented with 12.3%DM BPPCR (carinata meal 71.4% + pea 23.8% + lignosulfonate4.8%DM), and BPPCN = basal diet supplemented with 13.3%DM BPPCN (canola meal 71.4% + pea 23.8% + lignosulfonate 4.8%DM). In the whole project, nine mid-lactating Holstein cows (body weight, 679 ± 124 kg; days in milk, 96 ± 22) were used in a triplicated 3 × 3 Latin square study for an animal production performance study. For this fermentation and degradation kinetics study, the experiment was a 3 × 3 Latin square design with three different dietary treatments in three different periods with three available multiparous fistulated Holstein cows. The results showed that the control diet was higher (p < 0.05) in total VFA rumen concentration (138 mmol/L) than BPPCN. There was no dietary effect (p > 0.10) on the concentration of rumen ammonia and ruminal degradation kinetics of dietary nutrients. There was no significant differences (p > 0.10) among diets on the intestinal digestion of nutrients and metabolizable protein. Similarly, the feed milk values (FMV) were not affected (p > 0.10) by diets. In conclusion, the blend-pelleted products based on carinata meal for a new co-product from the bio-fuel processing industry was equal to the pelleted products based on conventional canola meal for high producing dairy cattle.
Effect of the N501Y Mutation on Ligands Complexed with SARS-CoV-2 RBD: Insights on Potential Drug Candidates for COVID-19
Authors: da Silva Camila Fonseca Amorim , Camalhonte Samanta Omae , de Oliveira Almeida Michell , Araujo Sheila Cruz , Sannomiya Miriam , Lago João Henrique Ghilardi , Honorio Kathia Maria
Published: May 2023

Bioactive compounds against SARS-CoV-2 targets could be potential treatments for COVID-19. Inhibitors of the receptor-binding domain (RBD) on the viral spike protein can block its binding to the human angiotensin-converting enzyme type II (ACE2) receptor. This study presents ligands based on natural products and synthetic compounds, targeting multiple N501/Y501 RBDs, besides RBD-ACE2, over different regions. The selected compounds were evaluated by docking using consensus scoring, pharmacokinetics/toxicological analyses, and molecular dynamics. Additionally, N501/Y501 RBD-ACE2 interaction properties and RBD–ligand complexes were compared. We identified that coenzyme Q10, 1-stearoyl-2-arachidonoylglycerol, and palmitone showed the greatest RBD interactions. Targeting specific residues (in particular, tyrosine) in the C-, N-terminal, and central RBD sites promoted more stable protein–ligand interactions than in the N-terminal region only. Our results indicate that the molecules had more energetically favorable interactions with residues from distinct RBD regions rather than only interacting with residues in the N-terminal site. Moreover, the compounds might better interact with mutated N501Y than N501 RBDs. These hits can be optimized to leads and investigated through QSAR models and biological assays to comprehend mechanisms better. Altogether, such strategies may anticipate antiviral strategies if or when future variants and other CoVs arise.
The Role of the Cardiac Biomarkers in the Renal Cell Carcinoma Multidisciplinary Management
Authors: Drăgan Anca , Sinescu Ioanel
Published: May 2023

Renal cell carcinoma, an aggressive malignancy, is often incidentally diagnosed. The patient remains asymptomatic to the late stage of the disease, when the local or distant metastases are already present. Surgical treatment remains the choice for these patients, although the plan must adapt to the characteristics of the patients and the extension of the neoplasm. Systemic therapy is sometimes needed. It includes immunotherapy, target therapy, or both, with a high level of toxicity. Cardiac biomarkers have prognosis and monitoring values in this setting. Their role in postoperative identification of myocardial injury and heart failure already have been demonstrated, as well as their importance in preoperative evaluation from the cardiac point of view and the progression of renal cancer. The cardiac biomarkers are also part of the new cardio-oncologic approach to establishing and monitoring systemic therapy. They are complementary tests for assessment of the baseline toxicity risk and tools to guide therapy. The goal must be to continue the treatment as long as possible with the initiation and optimisation of the cardiological treatment. Cardiac atrial biomarkers are reported to have also antitumoral and anti-inflammatory properties. This review aims to present the role of cardiac biomarkers in the multidisciplinary management of renal cell carcinoma patients.
Blood Basophils Relevance in Chronic Rhinosinusitis with Aspirin-Exacerbated Respiratory Disease
Authors: Brescia Giuseppe , Fabbris Cristoforo , Calvanese Leonardo , Bandolin Luigia , Pedruzzi Barbara , Di Pasquale Fiasca Valerio Maria , Marciani Silvia , Mularoni Francesca , Degli Esposti Pallotti Fabio , Negrisolo Michael , Spinato Giacomo , Frigo Anna Chiara , Marioni Gino
Published: May 2023

Aspirin-exacerbated respiratory disease (AERD) is characterized by eosinophilic asthma, chronic rhinosinusitis with nasal polyps (CRSwNP) and intolerance to cyclooxygenase-1 inhibitors. Interest is emerging in studying the role of circulating inflammatory cells in CRSwNP pathogenesis and its course, as well as their potential use for a patient-tailored approach. By releasing IL-4, basophils play a crucial role in activating the Th2-mediated response. The main aim of this study was to, first, investigate the level of the pre-operative blood basophils’ values, blood basophil/lymphocyte ratio (bBLR) and blood eosinophil-to-basophil ratio (bEBR) as predictors of recurrent polyps after endoscopic sinus surgery (ESS) in AERD patients. The secondary aim was to compare the blood basophil-related variables of the AERD series (study group) with those of a control group of 95 consecutive cases of histologically non-eosinophilic CRSwNP. The AERD group showed a higher recurrence rate than the control group (p < 0.0001). The pre-operative blood basophil count and pre-operative bEBR were higher in AERD patients than in the control group (p = 0.0364 and p = 0.0006, respectively). The results of this study support the hypothesis that polyps removal may contribute to reducing the inflammation and activation of basophils.
Automatic and Early Detection of Parkinson’s Disease by Analyzing Acoustic Signals Using Classification Algorithms Based on Recursive Feature Elimination Method
Authors: Alalayah Khaled M. , Senan Ebrahim Mohammed , Atlam Hany F. , Ahmed Ibrahim Abdulrab , Shatnawi Hamzeh Salameh Ahmad
Published: May 2023

Parkinson’s disease (PD) is a neurodegenerative condition generated by the dysfunction of brain cells and their 60–80% inability to produce dopamine, an organic chemical responsible for controlling a person’s movement. This condition causes PD symptoms to appear. Diagnosis involves many physical and psychological tests and specialist examinations of the patient’s nervous system, which causes several issues. The methodology method of early diagnosis of PD is based on analysing voice disorders. This method extracts a set of features from a recording of the person’s voice. Then machine-learning (ML) methods are used to analyse and diagnose the recorded voice to distinguish Parkinson’s cases from healthy ones. This paper proposes novel techniques to optimize the techniques for early diagnosis of PD by evaluating selected features and hyperparameter tuning of ML algorithms for diagnosing PD based on voice disorders. The dataset was balanced by the synthetic minority oversampling technique (SMOTE) and features were arranged according to their contribution to the target characteristic by the recursive feature elimination (RFE) algorithm. We applied two algorithms, t-distributed stochastic neighbour embedding (t-SNE) and principal component analysis (PCA), to reduce the dimensions of the dataset. Both t-SNE and PCA finally fed the resulting features into the classifiers support-vector machine (SVM), K-nearest neighbours (KNN), decision tree (DT), random forest (RF), and multilayer perception (MLP). Experimental results proved that the proposed techniques were superior to existing studies in which RF with the t-SNE algorithm yielded an accuracy of 97%, precision of 96.50%, recall of 94%, and F1-score of 95%. In addition, MLP with the PCA algorithm yielded an accuracy of 98%, precision of 97.66%, recall of 96%, and F1-score of 96.66%.
Two Rapid Power Iterative DOA Estimators for UAV Emitter Using Massive/Ultra-Massive Receive Array
Authors: Chen Yiwen , Jie Qijuan , Zhang Yiqiao , Shu Feng , Zhan Xichao , Yan Shihao , Cai Wenlong , Wang Xuehui , Sun Zhongwen , Zhang Peng , Chen Peng
Published: May 2023

To provide rapid direction finding (DF) for unmanned aerial vehicle (UAV) emitters in future wireless networks, a low-complexity direction of arrival (DOA) estimation architecture for massive multiple-input multiple-output (MIMO) receiver arrays is constructed. In this paper, we propose two strategies to address the extremely high complexity caused by eigenvalue decomposition of the received signal covariance matrix. Firstly, a rapid power iterative rotational invariance (RPI-RI) method is proposed, which adopts the signal subspace generated by power iteration to obtain the final direction estimation through rotational invariance between subarrays. RPI-RI causes a significant complexity reduction at the cost of a substantial performance loss. In order to further reduce the complexity and provide good directional measurement results, the rapid power iterative polynomial rooting (RPI-PR) method is proposed, which utilizes the noise subspace combined with the polynomial solution method to obtain the optimal direction estimation. In addition, the influence of initial vector selection on convergence in the power iteration is analyzed, especially when the initial vector is orthogonal to the incident wave. Simulation results show that the two proposed methods outperform the conventional DOA estimation methods in terms of computational complexity. In particular, the RPI-PR method achieves more than two orders of magnitude lower complexity than conventional methods and achieves performance close to the Cramér–Rao Lower Bound (CRLB). Moreover, it is verified that the initial vector and the relative error have a significant impact on the performance with respect to the computational complexity.
On Mathematics and Physics Teaching in Upper-Secondary School
Authors: Hansson Örjan , Juter Kristina , Redfors Andreas
Published: May 2023

This article reports on physics teaching in upper-secondary school with a focus on communication and relations made between mathematics, theoretical models in physics, and reality. Video data from four physics classrooms in three different teaching contexts, i.e., lessons, problem solving, and lab work, have been analysed by combining two theoretical frameworks: the Ternary Framework and Joint Action Theory in Didactics. Four physics teachers were selected from among a range of teachers who had responded to a web-based questionnaire, representing different teacher profiles from the questionnaire. The results indicate that the teacher profiles, including information on curriculum emphasis and views of mathematics, physics, and physics teaching, were good predictors for communication in the classrooms. The teacher profiles were found to influence teaching and the communication more than the teaching contexts. The benefits of formally correct mathematical treatment during physics teaching are discussed based on the results.
Investigating the Situation for Children with Autism and Their Families in Cambodia
Authors: Rose Richard , Jegannathan Bhoomikumar , Mong Dalin , Pat Puthy , Sok Derozet
Published: May 2023

Following periods of conflict and instability during the oppressive regime of the Khmer Rouge (1975–1978) and the period of Vietnamese occupation (1978–1992), the Kingdom of Cambodia has adopted policies and initiatives that aim to ensure greater equity and stability across all services in the country as a signatory to international agreements for the promotion of universal primary education (United Nations 2015). The education of children with disabilities continues to present challenges to both policy makers and service providers in Cambodia, though government agencies have made a commitment and invested resources to improve facilities and increase awareness of the difficulties experienced by children and families. Previous studies of provision for children on the autism spectrum in Cambodia suggest that they are little understood and that many experience difficulties accessing appropriate services or support. However, these reports have often been based on localised small-scale studies and have not provided a broader national perspective of the situation. A national analysis of the situation for persons with autism was conducted to provide a more detailed picture of the experiences of children with autistic spectrum disorders and their families. Data were collated using focus groups and interviews with service users and providers from a purposive stratified sample across the country. The findings reveal that a limited awareness and understanding of autism amongst both professionals and the general public has limited opportunities for development. Education facilities and expertise are limited, and access to therapeutic and specialist medical provision is poor. The pervasive nature of poverty has been a major contributory factor in the slow development of and accessibility to services to this population. A number of recommendations have been made and are being used to shape future policies for children with autism and their families in Cambodia.
A Portable Soft Exosuit to Assist Stair Climbing with Hip Flexion
Authors: Xu Yinsheng , Li Weimin , Chen Chunjie , Chen Shaocong , Wang Zhuo , Yang Fangliang , Liu Yao , Wu Xinyu
Published: May 2023

Soft exosuits are an emerging class of robots that have been shown to significantly reduce the metabolic cost of daily human movement. However, most soft exosuits are currently being studied for walking and running, and relatively minor research has been carried out on exosuits for stair climbing. Numerous exoskeletons used for stair climbing have a more rigid structure and are heavier, which may result in a greater force required by the wearer to overcome the weight from the exoskeleton when ascending stairs, which can result in metabolic costs. As a result, a reduction in rigid structures can reduce the weight of the exoskeleton and further reduce metabolic costs during stair climbing. In this paper, a waist-wearable soft exosuit was designed that assists hip flexion to aid stair climbing in older adults, in order to demonstrate the importance of choosing to assist hip flexion during stair climbing. An admittance delayed feedback control method was also proposed to use the angular information measured by the IMUs to enable the exosuit to adapt to different staircases. Metabolic experiments have shown that people who use soft exosuits have an average decrease of 6.9% in metabolism when they climb stairs than those who do not. The muscle fatigue experiments demonstrated a reduction in muscle fatigue of approximately 9.35%, 38.75% and 9.65% for the rectus femoris, lateral femoris and gastrocnemius muscles, respectively, when compared to cases without the soft exosuit. The results show that assisted hip flexion during stair climbing is a reasonable approach to effectively reduce metabolic consumption and muscle fatigue.