bluuebunny/crossref_metadata_2025 huggingface dataset:
Antiproliferative Activity, Multikinase Inhibition, Apoptosis- Inducing Effects and Molecular Docking of Novel Isatin–Purine Hybrids
Authors: Alanazi Ashwag S. , Mirgany Tebyan O. , Alsfouk Aisha A. , Alsaif Nawaf A. , Alanazi Mohammed M.
Published: March 2023

The traditional single-treatment strategy for cancer is frequently unsuccessful due to the complexity of cellular signaling. However, suppression of multiple targets is vital to defeat tumor cells. In this research, new compounds for the treatment of cancer were developed successfully as novel hybrid anticancer agents. Based on a molecular hybridization strategy, we designed hybrid agents that target multiple protein kinases to fight cancer cells. The proposed hybrid agents combined purine and isatin moieties in their structures with 4-aminobenzohydrazide and hydrazine as different linkers. Having those two moieties in one molecule enabled the capability to inhibit multiple kinases, such as human epidermal receptor (EGFR), human epidermal growth factor receptor 2 (HER2), vascular endothelial growth factor receptor 2 (VEGFR2) and cyclin-dependent kinase 2 (CDK2). Anticancer activity was evaluated by performing cytotoxicity assays, kinase inhibition assays, cell cycle analysis, and BAX, Bcl-2, Caspase 3 and Caspase 9 protein level determination assays. The results showed that the designed hybrids tackled the cancer by inhibiting both cell proliferation and metastasis. A molecular docking study was performed to predict possible binding interactions in the active site of the investigated protein kinase enzymes.
The Survival Outcomes of Patients Requiring Prolonged Mechanical Ventilation
Authors: Huang Chienhsiu
Published: March 2023

Background and objectives: Patients who require prolonged mechanical ventilation typically experience poor long-term survival outcomes. However, there have been few studies conducted to investigate the five-year survival rate of these patients. This study aims to determine the factors that affect the five-year survival rate of patients who require prolonged mechanical ventilation, with the goal of improving their survival outcomes. Materials and Methods: The current retrospective, single-center study included all patients who required prolonged mechanical ventilation over a period of six years. We collected data on their age, sex, causes of acute respiratory failure leading to prolonged mechanical ventilation, comorbidities, receipt of a tracheostomy or not, weaning status, discharge conditions, and long-term outcomes. Results: The study examined the long-term outcomes of 403 patients who required prolonged mechanical ventilation until December 2018. Of the study population, 157 patients were successfully weaned from prolonged mechanical ventilation and discharged, 186 patients passed away in the hospital, and 60 patients remained ventilator-dependent. For all 403 patients receiving prolonged mechanical ventilation, the one-year and five-year survival rates were 24.3% and 14.6%, respectively. Among the 243 patients who were successfully weaned from prolonged mechanical ventilation, the corresponding rates were 32.6% and 21.0%. For the 157 discharged prolonged mechanical ventilation patients, the one-year and five-year survival rates were 50.3% and 32.6%, respectively. For the 60 ventilator-dependent patients, the one-year and five-year survival rates were 31.7% and 13.2%, respectively. The study revealed that successfully weaned from invasive mechanical ventilation and the receipt of a tracheostomy were influential factors in the five-year survival rate of patients requiring prolonged mechanical ventilation. Conclusions: Patients requiring prolonged mechanical ventilation may experience poor survival outcomes. Nevertheless, two key factors that can improve their long-term survival are successfully weaned from invasive mechanical ventilation and receipt of a tracheostomy.
Hereditary Congenital Methemoglobinemia Diagnosed at the Age of 79 Years: A Case Report
Authors: Nakata Marohito , Yokota Naoko , Tabata Kazuhiko , Morikawa Takuya , Shibata Hiroki , Kenzaka Tsuneaki
Published: March 2023

Background: Cardiopulmonary disorders are the most common cause of central cyanosis, and methemoglobinemia is often overlooked in the differential diagnosis of patients with central cyanosis. In most cases, methemoglobinemia is acquired and hereditary congenital methemoglobinemia is rare. Only a few case reports of congenital methemoglobinemia can be found in PubMed. To date, only four cases of congenital methemoglobinemia diagnosed after the age of 50 years have been reported. Case Presentation: A 79-year-old Japanese woman presented at our hospital with the chief complaints of dyspnea and cyanosis. She exhibited cyanosis of the lips and extremities, and her SpO2 was 80%, with oxygen administration at 5 L/min. Blood gas analysis revealed a PaO2 of 325.4 mmHg and methemoglobin level of 36.9%. The SpO2 and PaO2 values were dissociated, and methemoglobin levels were markedly elevated. Genetic analysis revealed a nonsynonymous variant in the gene encoding nicotinamide adenine dinucleotide cytochrome (NADH) B5 reductase 3 (CYB5R3), and the patient was diagnosed with congenital methemoglobinemia. Conclusions: It is important to consider methemoglobinemia in the differential diagnosis of patients with central cyanosis. At 79 years of age, our patient represents the oldest patient with this diagnosis. This report indicates that it is crucial to consider the possibility of methemoglobinemia regardless of the patient’s age.
Factors Associated with Psychotropic Medications Literacy among Community Pharmacists
Authors: Alqudah Abdelrahim , Al-Taani Ghaith , Handal Daniel , Al Sharab Rahaf , Al Shreideh Rawan , Al-Smadi Ahmed , Qnais Esam , Gammoh Omar
Published: March 2023

Background and objectives: Community pharmacists play an important role in ensuring the patient’s adherence to medications, thus achieving therapeutic outcomes. The present study had two aims: to measure the extent of knowledge that community pharmacists had about psychotropic medications and to determine the factors associated with higher knowledge scores. Methods: A cross-sectional design was employed, using a structured online questionnaire. The study instrument assessed demographics, general practice characteristics related to psychotropics and a battery of factual questions that assessed the knowledge of pharmacists about psychotropic medications using closed-ended responses. A total knowledge score consisting of the sum of correct responses was calculated; the passing score was 75%. A total of 676 pharmacists completed the survey. Results: Only 20% passed the threshold score (75%) for the factual knowledge questions, and only (11.0%) were very comfortable with their knowledge of psychotropic agents. A total of 49.0% of the respondents felt that they had been adequately trained to counsel patients on psychotropic agents. According to the regression model, pharmacists who reported higher knowledge were more experienced (0.63, (0.26–1.0), p < 0.001), reported studying the topic in the pharmacy school (0.77 (0.27–1.26), p = 0.002) holding a Doctor of Pharmacy (Pharm D) degree (0.24 (0.05–0.43), p = 0.01), and reported a higher perceived knowledge (0.29 (0.01–0.38), p = 0.038). Conclusion: Community pharmacists reported poor knowledge of psychotropic medications, and continuous medical and professional education programs are mandatory.
Charting the Journey of Young Leaders: A New Model of Transferability of Skills
Authors: Karagianni Despoina , Lainidi Olga , Montgomery Anthony
Published: March 2023

Globally, adolescents and young adults are calling for action from governments on global humanitarian crises, taking on leadership roles that have contributed to redefining leadership in terms of behavior and action rather than qualities and status. However, there is a significant gap with regard to the conceptual and theoretical understanding of how adolescents and young adults experience leadership. In this paper, we present the results of two qualitative studies that examined the phenomenon of leadership among adolescents and young adults. Study 1 involved interviews with young adult leaders to analyze the fit between traditional leadership theories and their experience of leadership. Following this, Study 2 utilized the results from Study 1 to design a diary study of adolescents attending a leadership program. Both studies revealed that leadership is experienced as a pathway that involves three mechanisms of transferability: sensemaking, action and reflection. The findings of the studies are contrasted with traditional models of leadership that underrepresent the developmental nature of leadership and the transferability of leadership skills across different environments.
An Ultrasonic Target Detection System Based on Piezoelectric Micromachined Ultrasonic Transducers
Authors: Gao Mingze , Tong Zhihao , Wu Zhipeng , Lou Liang
Published: March 2023

In this paper, an ultrasonic target detection system based on Piezoelectric Micromachined Ultrasonic Transducers (PMUTs) is proposed, which consists of the PMUTs based ultrasonic sensor and the sensor system. Two pieces of 3 × 3 PMUTs arrays with the resonant frequency of 115 kHz are used as transmitter and receiver of the PMUTs-based ultrasonic sensor. Then, the sensor system can calculate the target’s position through the signal received by the above receiver. The static and dynamic performance of the proposed prototype system are characterized on black, white, and transparent targets. The experiment results demonstrated that the proposed system can detect targets of different colors, transparencies, and motion states. In the static experiments, the static location errors of the proposed system in the range of 200 mm to 320 mm are 0.51 mm, 0.50 mm and 0.53 mm, whereas the errors of a commercial laser sensor are 2.89 mm, 0.62 mm, and N\A. In the dynamic experiments, the experimental materials are the targets with thicknesses of 1 mm, 1.5 mm, 2 mm and 2.5 mm, respectively. The proposed system can detect the above targets with a maximum detection error of 4.00%. Meanwhile, the minimum resolution of the proposed system is about 0.5 mm. Finally, in the comprehensive experiments, the proposed system successfully guides a robotic manipulator to realize the detecting, grasping, and moving of a transparent target with 1 mm. This ultrasonic target detection system has demonstrated a cost-effective method to detect targets, especially transparent targets, which can be widely used in the detection and transfer of glass substrates in automated production lines.
Sharpless Asymmetric Dihydroxylation: An Impressive Gadget for the Synthesis of Natural Products: A Review
Authors: Mushtaq Aqsa , Zahoor Ameer Fawad , Bilal Muhammad , Hussain Syed Makhdoom , Irfan Muhammad , Akhtar Rabia , Irfan Ali , Kotwica-Mojzych Katarzyna , Mojzych Mariusz
Published: March 2023

Sharpless asymmetric dihydroxylation is an important reaction in the enantioselective synthesis of chiral vicinal diols that involves the treatment of alkene with osmium tetroxide along with optically active quinine ligand. Sharpless introduced this methodology after considering the importance of enantioselectivity in the total synthesis of medicinally important compounds. Vicinal diols, produced as a result of this reaction, act as intermediates in the synthesis of different naturally occurring compounds. Hence, Sharpless asymmetric dihydroxylation plays an important role in synthetic organic chemistry due to its undeniable contribution to the synthesis of biologically active organic compounds. This review emphasizes the significance of Sharpless asymmetric dihydroxylation in the total synthesis of various natural products, published since 2020.
Towards the Sustainable Exploitation of Salt-Tolerant Plants: Nutritional Characterisation, Phenolics Composition, and Potential Contaminants Analysis of Salicornia ramosissima and Sarcocornia perennis alpini
Authors: Lopes Maria , Silva Ana Sanches , Séndon Raquel , Barbosa-Pereira Letricia , Cavaleiro Carlos , Ramos Fernando
Published: March 2023

Increasing soil salinisation represents a serious threat to food security, and therefore the exploitation of high-yielding halophytes, such as Salicornia and Sarcocornia, needs to be considered not merely in arid regions but worldwide. In this study, Salicornia ramosissima and Sarcocornia perennis alpini were evaluated for nutrients, bioactive compounds, antioxidant capacity, and contaminants. Both were shown to be nutritionally relevant, exhibiting notable levels of crude fibre and ash, i.e., 11.26–15.34 and 39.46–40.41% dry weight (dw), respectively, and the major minerals were Na, K, and Mg. Total phenolics thereof were 67.05 and 38.20 mg of gallic acid equivalents/g extract dw, respectively, mainly p-coumaric acid and quercetin. Both species displayed antioxidant capacity, but S. ramossima was prominent in both the DPPH and ß-carotene bleaching assays. Aflatoxin B1 was detected in S. ramosissima, at 5.21 µg/Kg dw, which may pose a health threat. The Cd and Pb levels in both were low, but the 0.01 mg/Kg Hg in S. perennis alpini met the maximum legal limit established for marine species including algae. Both species exhibit high potential for use in the agro-food, cosmetics, and pharmaceutical sectors, but specific regulations and careful cultivation strategies need to be implemented, in order to minimise contamination risks by mycotoxins and heavy metals.
Steered Molecular Dynamics Simulations Study on FABP4 Inhibitors
Authors: Tomarchio Rosario , Patamia Vincenzo , Zagni Chiara , Crocetti Letizia , Cilibrizzi Agostino , Floresta Giuseppe , Rescifina Antonio
Published: March 2023

Ordinary small molecule de novo drug design is time-consuming and expensive. Recently, computational tools were employed and proved their efficacy in accelerating the overall drug design process. Molecular dynamics (MD) simulations and a derivative of MD, steered molecular dynamics (SMD), turned out to be promising rational drug design tools. In this paper, we report the first application of SMD to evaluate the binding properties of small molecules toward FABP4, considering our recent interest in inhibiting fatty acid binding protein 4 (FABP4). FABP4 inhibitors (FABP4is) are small molecules of therapeutic interest, and ongoing clinical studies indicate that they are promising for treating cancer and other diseases such as metabolic syndrome and diabetes.
A Comprehensive Review of Natural Flavonoids with Anti-SARS-CoV-2 Activity
Authors: Yang Jun-Yu , Ma Yi-Xuan , Liu Yan , Peng Xiang-Jun , Chen Xiang-Zhao
Published: March 2023

The COVID-19 pandemic caused by SARS-CoV-2 has majorly impacted public health and economies worldwide. Although several effective vaccines and drugs are now used to prevent and treat COVID-19, natural products, especially flavonoids, showed great therapeutic potential early in the pandemic and thus attracted particular attention. Quercetin, baicalein, baicalin, EGCG (epigallocatechin gallate), and luteolin are among the most studied flavonoids in this field. Flavonoids can directly or indirectly exert antiviral activities, such as the inhibition of virus invasion and the replication and inhibition of viral proteases. In addition, flavonoids can modulate the levels of interferon and proinflammatory factors. We have reviewed the previously reported relevant literature researching the pharmacological anti-SARS-CoV-2 activity of flavonoids where structures, classifications, synthetic pathways, and pharmacological effects are summarized. There is no doubt that flavonoids have great potential in the treatment of COVID-19. However, most of the current research is still in the theoretical stage. More studies are recommended to evaluate the efficacy and safety of flavonoids against SARS-CoV-2.
Untargeted Metabolomic Analysis and Chemometrics to Identify Potential Marker Compounds for the Chemical Differentiation of Panax ginseng, P. quinquefolius, P. notoginseng, P. japonicus, and P. japonicus var. major
Authors: Ji Ruifeng , Garran Thomas Avery , Luo Yilu , Cheng Meng , Ren Mengyue , Zhou Xiuteng
Published: March 2023

The Panax L. genus is well-known for many positive physiological effects on humans, with major species including P. ginseng, P. quinquefolius, P. notoginseng, P. japonicus, and P. japonicus var. major, the first three of which are globally popular. The combination of UPLC-QTOF-MS and chemometrics were developed to profile “identification markers” enabling their differentiation. The establishment of reliable biomarkers that embody the intrinsic metabolites differentiating species within the same genus is a key in the modernization of traditional Chinese medicine. In this work, the metabolomic differences among these five species were shown, which is critical to ensure their appropriate use. Consequently, 49 compounds were characterized, including 38 identified robust biomarkers, which were mainly composed of saponins and contained small amounts of amino acids and fatty acids. VIP (projection variable importance) was used to identify these five kinds of ginseng. In conclusion, by illustrating the similarities and differences between the five species of ginseng with the use of an integrated strategy of combining UPLC-QTOF-MS and multivariate analysis, we provided a more efficient and more intelligent manner for explaining how the species differ and how their secondary metabolites affect this difference. The most important biomarkers that distinguished the five species included Notoginsenoside-R1, Majonoside R1, Vinaginsenoside R14, Ginsenoside-Rf, and Ginsenoside-Rd.
Investigation of Molecular Mechanism of Cobalt Porphyrin Catalyzed CO2 Electrochemical Reduction in Ionic Liquid by In-Situ SERS
Authors: Wu Feng , Jiang Fengshuo , Yang Jiahao , Dai Weiyan , Lan Donghui , Shen Jing , Fang Zhengjun
Published: March 2023

This study explores the electrochemical reduction in CO2 using room temperature ionic liquids as solvents or electrolytes, which can minimize the environmental impact of CO2 emissions. To design effective CO2 electrochemical systems, it is crucial to identify intermediate surface species and reaction products in situ. The study investigates the electrochemical reduction in CO2 using a cobalt porphyrin molecular immobilized electrode in 1-n-butyl-3-methyl imidazolium tetrafluoroborate (BMI.BF4) room temperature ionic liquids, through in-situ surface-enhanced Raman spectroscopy (SERS) and electrochemical technique. The results show that the highest faradaic efficiency of CO produced from the electrochemical reduction in CO2 can reach 98%. With the potential getting more negative, the faradaic efficiency of CO decreases while H2 is produced as a competitive product. Besides, water protonates porphyrin macrocycle, producing pholorin as the key intermediate for the hydrogen evolution reaction, leading to the out-of-plane mode of the porphyrin molecule. Absorption of CO2 by the ionic liquids leads to the formation of BMI·CO2 adduct in BMI·BF4 solution, causing vibration modes at 1100, 1457, and 1509 cm−1. However, the key intermediate of CO2−· radical is not observed. The υ(CO) stretching mode of absorbed CO is affected by the electrochemical Stark effect, typical of CO chemisorbed on a top site.
Experimental Study on Electrochemical Desulfurization of Coal Liquefaction Residue
Authors: Fan Jianming , Zhang Yongfeng , Li Na , Bai Ruzhan , Liu Qi , Zhou Xing
Published: March 2023

The occurrence of sulfur in coal direct liquefaction residue affects its further high quality and high value utilization. Electrochemical desulfurization is characterized by mild reaction conditions, simple operation, easy separation of sulfur conversion products and little influence on the properties of the liquefied residue. An anodic electrolytic oxidation desulphurization experiment was carried out on the liquefaction residue of the by-product of a coal-to-liquid enterprise in the slurry state. An electrochemical test and material characterization of raw materials before and after electrolysis showed that electrolytic oxidation can desulfurize the liquefaction residue under an alkaline condition. Linear sweep voltammetry (LSV) was used for the electrolysis experiments to obtain the optimal slurry concentration of 60 g/L. On this basis, the reaction kinetics were calculated, and the minimum activation energy in the interval at 0.9 (V vs. Hg/HgO) was 19.71 kJ/mol. The relationship between the electrolytic desulfurization of the liquefied residue and energy consumption was studied by the potentiostatic method. The influence of anodic potential and electrolytic temperature on the current density, cell voltage, desulfurization rate and energy consumption was investigated. The experimental results showed that the desulfurization rate and total energy consumption increase positively with the increase in reaction temperature and electrolytic potential in a certain range. The influence of the reaction temperature on the desulfurization rate and total energy consumption is more prominent than that of electrolytic potential, but the energy consumption of sulfur removal per unit mass does not show a positive correlation. Therefore, with the energy consumption per unit mass of sulfur removal as the efficiency index, the optimal experimental results were obtained: under the conditions of 0.8 (V vs. Hg/HgO) anode potential, 50 °C electrolytic temperature, 60 g/L slurry concentration and 14,400 s electrolytic time, the desulfurization rate was 18.85%, and the power consumption per unit mass of sulfur removal was 5585.74 W·s/g. The results of XPS, SEM, BET and IC showed that both inorganic and organic sulfur were removed by electrolytic oxidation, and the morphology, pore structure and chemical bond of the liquefied residue were affected by electrolytic oxidation. The research method provides a new idea and reference for the efficiency evaluation of desulfurization and hydrogen production from coal liquefaction residue.
MALDI MSI Separation of Same Donor’s Fingermarks Based on Time of Deposition—A Proof-of-Concept Study
Authors: Frisch Kim , Nielsen Kristine Lykke , Francese Simona
Published: March 2023

Despite the advent of DNA profiling, fingerprints still play an important role in suspect identification. However, if single crime scene marks may be challenging to identify, overlapping fingermarks, understandably, pose an even greater challenge. In the last decade, mass spectrometry-imaging methods have provided a possible solution to the separation of fingermarks from two or more donors, based on the differential chemical composition. However, there are no studies attempting to separate overlapping marks from the same donor. This is important in relation to fingermark deposition at different times, which could be critical, for example, to ascertain legitimate access to the scene. In the work presented here, we investigate whether Matrix-Assisted Laser Desorption Ionisation Mass Spectrometry Imaging can separate the same donor’s fingermarks deposited at different times based on intra-donor fingermark composition variability. Additionally, the hypothesis that the different times of deposition could be also determined was investigated in the view of linking the suspect at the scene at different times; the dating window of MALDI MSI within the selected molecular range was explored. Results show that it is possible to separate overlapping fingermarks from the same donor in most cases, even from natural marks. Fresh marks (0 days) could be separated from those of fourteen days of age, though the latter could not be distinguished from the set aged for seven days. Due to the use of only one donor, these are to be considered preliminary data, though findings are interesting enough to warrant further investigation of the capabilities and limitations of this approach using a larger cohort of donors.
The Identification of SQS/SQE/OSC Gene Families in Regulating the Biosynthesis of Triterpenes in Potentilla anserina
Authors: Jiao Yangmiao , Li Xu , Huang Xueshuang , Liu Fan , Zhang Zaiqi , Cao Liang
Published: March 2023

The tuberous roots of Potentilla anserina (Pan) are an edible and medicinal resource in Qinghai–Tibetan Plateau, China. The triterpenoids from tuberous roots have shown promising anti-cancer, hepatoprotective, and anti-inflammatory properties. In this study, we carried out phylogenetic analysis of squalene synthases (SQSs), squalene epoxidases (SQEs), and oxidosqualene cyclases (OSCs) in the pathway of triterpenes. In total, 6, 26, and 20 genes of SQSs, SQEs, and OSCs were retrieved from the genome of Pan, respectively. Moreover, 6 SQSs and 25 SQEs genes expressed in two sub-genomes (A and B) of Pan. SQSs were not expanded after whole-genome duplication (WGD), and the duplicated genes were detected in SQEs. Twenty OSCs were divided into two clades of cycloartenol synthases (CASs) and β-amyrin synthases (β-ASs) by a phylogenetic tree, characterized with gene duplication and evolutionary divergence. We speculated that β-ASs and CASs may participate in triterpenes synthesis. The data presented act as valuable references for future studies on the triterpene synthetic pathway of Pan.
Artemisia vestita: A Folk Medicine with Hidden Herbal Fortune
Authors: Dogra Shivani , Singh Joginder , Koul Bhupendra , Yadav Dhananjay
Published: March 2023

Traditional medicines are nature’s gift and our native heritage, which play a vital role in maintaining a disease-free life. Artemisia vestita Wall. ex Besser (family: Asteraceae), popularly known as “Kubsha” or “Russian wormwood”, is a highly enriched folklore medicine with wound- healing, antiphlogistic, antifebrile, antifeedant, anti-helminthic, antimicrobial, antiviral, antitumor, and antiproliferative potential attributed to the presence of various volatile and non-volatile secondary metabolites. A systematic and extensive review of the literature on A. vestita was carried out via the Web of Science, PubMed, INMEDPLAN, EMBASE, Google Scholar, and NCBI, as well as from several websites. The highly relevant literature contained in 109 references was selected for further inclusion in this review. A total of 202 bioactive compounds belonging to different chemical classes such as terpenoids, coumarins, flavonoids, alkaloids, acetylenes, tannins, carotenoids, and sterols have been reported in A. vestita, which are responsible for different pharmacological activities. The chemical structures obtained from the PubChem and Chem Spider databases were redrawn using the software Chem Draw® version 8.0. This review paper summarizes the distribution, botanical description, phytochemistry, pharmacological activities, and conservation of A. vestita, which will assist scientists for further investigation. Extensive studies on the active constituents, pharmaceutical standardization, mode of action, and sustainable conservation of A. vestita are needed to further explore its wound-healing and allied medicinal properties.
The Mechanism of Kelulut Honey in Reversing Metabolic Changes in Rats Fed with High-Carbohydrate High-Fat Diet
Authors: Hashim Khairun-Nisa , Chin Kok-Yong , Ahmad Fairus
Published: March 2023

Metabolic syndrome (MetS) is composed of central obesity, hyperglycemia, dyslipidemia and hypertension that increase an individual’s tendency to develop type 2 diabetes mellitus and cardiovascular diseases. Kelulut honey (KH) produced by stingless bee species has a rich phenolic profile. Recent studies have demonstrated that KH could suppress components of MetS, but its mechanisms of action are unknown. A total of 18 male Wistar rats were randomly divided into control rats (C group) (n = 6), MetS rats fed with a high carbohydrate high fat (HCHF) diet (HCHF group) (n = 6), and MetS rats fed with HCHF diet and treated with KH (HCHF + KH group) (n = 6). The HCHF + KH group received 1.0 g/kg/day KH via oral gavage from week 9 to 16 after HCHF diet initiation. Compared to the C group, the MetS group experienced a significant increase in body weight, body mass index, systolic (SBP) and diastolic blood pressure (DBP), serum triglyceride (TG) and leptin, as well as the area and perimeter of adipocyte cells at the end of the study. The MetS group also experienced a significant decrease in serum HDL levels versus the C group. KH supplementation reversed the changes in serum TG, HDL, leptin, adiponectin and corticosterone levels, SBP, DBP, as well as adipose tissue 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) level, area and perimeter at the end of the study. In addition, histological observations also showed that KH administration reduced fat deposition within hepatocytes, and prevented deterioration of pancreatic islet and renal glomerulus. In conclusion, KH is effective in preventing MetS by suppressing leptin, corticosterone and 11βHSD1 levels while elevating adiponectin levels.
Year I—Introducing NDT: A New Journal on Non-Destructive Testing Science, Technology and Their Applications
Authors: Tosti Fabio
Published: March 2023

It is with great pleasure that the journal NDT (ISSN 2813-477X) [...]
Global Scientific Trends on Healthy Eating from 2002 to 2021: A Bibliometric and Visualized Analysis
Authors: Fang Te , Cao Hongyi , Wang Yue , Gong Yang , Wang Zhongqing
Published: March 2023

Diet has been recognized as a vital risk factor for non-communicable diseases (NCDs), climate changes, and increasing population, which has been reflected by a rapidly growing body of the literature related to healthy eating. To reveal a panorama of the topics related to healthy eating, this study aimed to characterize and visualize the knowledge structure, hotspots, and trends in this field over the past two decades through bibliometric analyses. Publications related to healthy eating between 1 January 2002 and 31 December 2021 were retrieved and extracted from the Web of Science database. The characteristics of articles including publication years, journals, authors, institutions, countries/regions, references, and keywords were assessed. The analyses on co-authorship, co-occurrence, and co-citation were performed and network visualization maps were constructed by VOSviewer. Major subdomains identified by bibliometrics were further discussed and analyzed. A total of 12,442 articles on healthy eating were identified. Over the past two decades, the annual global publications increased from 71 to 1764, showing a nearly 25-fold growth. The journal Nutrients published the most articles and The American Journal of Clinical Nutrition possessed the highest citations. The United States, Harvard University, and Hu, Frank B. were identified as the most productive and influential country, institution, and author, respectively. The co-occurrence cluster analysis of the top 100 keywords formed four clusters: (1) the food insecurity environment for youths highlighting the necessity and significance of implementing healthy eating in early life; (2) sustainable advantages of the Mediterranean diet; (3) the importance of an overall healthy lifestyle optimization leveraged by eHealth; (4) the challenges during the course of healthy eating against obesity, which are prominent in reflecting the knowledge structure, hotspots, and trends. Moreover, COVID-19, orthorexia nervosa, sustainability, microbiota, food insecurity, and e-health are identified keywords that represented the latest high-frequency keywords and indicated the emerging frontiers of healthy eating. This study indicates that the number of publications on healthy eating will increase in the future and that healthy dietary patterns and clinical applications of healthy eating will be the next hotspots in this research field.
Radiological Benefits of Vitamin D Status and Supplementation in Patients with MS—A Two-Year Prospective Observational Cohort Study
Authors: Galus Weronika , Chmiela Tomasz , Walawska-Hrycek Anna , Krzystanek Ewa
Published: March 2023

Current data emphasize the immunomodulating role of vitamin D in enhancing the anti-inflammatory response. Vitamin D deficiency is an established risk factor for developing multiple sclerosis—the autoimmune demyelinating and degenerative disease of the central nervous system. Several studies confirmed that higher vitamin D serum level is associated with better clinical and radiological outcomes in patients with multiple sclerosis, whereas vitamin D supplementation benefits in multiple sclerosis remain inconclusive. Despite that, many experts suggest regular measurements of vitamin D serum levels and supplementation in patients with multiple sclerosis. In this study, 133 patients with multiple sclerosis (relapsing–remitting subtype) were prospectively observed in a 0-, 12- and 24-month time span in a clinical setting. The study group consisted of 71.4% of patients (95 out of 133) supplementing vitamin D. The associations between vitamin D serum levels, clinical outcomes (disability status expressed by EDSS, number of relapses and time to relapse) and radiological outcomes (new T2-weighted lesions and number of gadolinium-enhanced lesions) were evaluated. There were no statistically significant correlations between clinical outcomes and vitamin D serum levels or supplementations. Fewer new T2-weighted lesions were observed in patients with vitamin D supplementations (p = 0.034) in 24 months of observation. Moreover, an optimal or higher level of vitamin D (>30 ng/mL) maintained throughout the entire observation period was associated with a lower number of new T2-weighted lesions in 24 months of observation (p = 0.045). These results support vitamin D implementation commencement and amelioration in patients with multiple sclerosis.
Serum and Urinary Soluble α-Klotho as Markers of Kidney and Vascular Impairment
Authors: Martín-Vírgala Julia , Fernández-Villabrille Sara , Martín-Carro Beatriz , Tamargo-Gómez Isaac , Navarro-González Juan F. , Mora-Fernández Carmen , Calleros Laura , Astudillo-Cortés Elena , Avello-Llano Noelia , Mariño Guillermo , Dusso Adriana S. , Alonso-Montes Cristina , Panizo Sara , Cannata-Andía Jorge B. , Naves-Díaz Manuel , Carrillo-López Natalia
Published: March 2023

This study was designed to investigate the controversy on the potential role of sKlotho as an early biomarker in Chronic Kidney Disease–Mineral Bone Disorder (CKD-MBD), to assess whether sKlotho is a reliable marker of kidney α-Klotho, to deepen the effects of sKlotho on vascular smooth muscle cells (VSMCs) osteogenic differentiation and to evaluate the role of autophagy in this process. Experimental studies were conducted in CKD mice fed a normal phosphorus (CKD+NP) or high phosphorus (CKD+HP) diet for 14 weeks. The patients’ study was performed in CKD stages 2–5 and in vitro studies which used VSMCs exposed to non-calcifying medium or calcifying medium with or without sKlotho. The CKD experimental model showed that the CKD+HP group reached the highest serum PTH, P and FGF23 levels, but the lowest serum and urinary sKlotho levels. In addition, a positive correlation between serum sKlotho and kidney α-Klotho was found. CKD mice showed aortic osteogenic differentiation, together with increased autophagy. The human CKD study showed that the decline in serum sKlotho is previous to the rise in FGF23. In addition, both serum sKlotho and FGF23 levels correlated with kidney function. Finally, in VSMCs, the addition of sKlotho prevented osteogenic differentiation and induced autophagy. It can be concluded that serum sKlotho was the earliest CKD-MBD biomarker, a reliable indicator of kidney α-Klotho and that might protect against osteogenic differentiation by increasing autophagy. Nevertheless, further studies are needed to investigate the mechanisms of this possible protective effect.
Proteomic Analysis Reveals Changes in Tight Junctions in the Small Intestinal Epithelium of Mice Fed a High-Fat Diet
Authors: Muto Hisanori , Honda Takashi , Tanaka Taku , Yokoyama Shinya , Yamamoto Kenta , Ito Takanori , Imai Norihiro , Ishizu Yoji , Maeda Keiko , Ishikawa Tetsuya , Adachi Shungo , Sato Chikara , Tsuji Noriko M. , Ishigami Masatoshi , Fujishiro Mitsuhiro , Kawashima Hiroki
Published: March 2023

The impact of a high-fat diet (HFD) on intestinal permeability has been well established. When bacteria and their metabolites from the intestinal tract flow into the portal vein, inflammation in the liver is triggered. However, the exact mechanism behind the development of a leaky gut caused by an HFD is unclear. In this study, we investigated the mechanism underlying the leaky gut related to an HFD. C57BL/6J mice were fed an HFD or control diet for 24 weeks, and their small intestine epithelial cells (IECs) were analyzed using deep quantitative proteomics. A significant increase in fat accumulation in the liver and a trend toward increased intestinal permeability were observed in the HFD group compared to the control group. Proteomics analysis of the upper small intestine epithelial cells identified 3684 proteins, of which 1032 were differentially expressed proteins (DEPs). Functional analysis of DEPs showed significant enrichment of proteins related to endocytosis, protein transport, and tight junctions (TJ). Expression of Cldn7 was inversely correlated with intestinal barrier function and strongly correlated with that of Epcam. This study will make important foundational contributions by providing a comprehensive depiction of protein expression in IECs affected by HFD, including an indication that the Epcam/Cldn7 complex plays a role in leaky gut.
Very Low and High Levels of Vitamin D Are Associated with Shorter Leukocyte Telomere Length in 148,321 UK Biobank Participants
Authors: Kuo Chia-Ling , Kirk Ben , Xiang Meiruo , Pilling Luke C. , Kuchel George A. , Kremer Richard , Duque Gustavo
Published: March 2023

Background: Shorter leukocyte telomere length (LTL) is observed in multiple age-related diseases, which are also associated with vitamin D deficiency (i.e., osteosarcopenia, neurocognitive disorders, cancer, osteoarthritis, etc.), suggesting a close association between vitamin D and LTL. In this study, we examined the relationship between vitamin D levels and LTL in older participants of the UK Biobank. Methods: Data were collected from the UK Biobank. Participants aged 60 and older (n = 148,321) were included. Baseline LTL was measured using a multiplex qPCR technique and expressed as the ratio of the telomere amplification product (T) to that of a single-copy gene (S) (T/S ratio). Serum 25-hydroxyvitamin D (25OHD) was stratified by z score and linked to LTL in a linear regression model adjusting for covariates. Results: Compared to the medium level, a low (in the range of 16.6 nmol/L, 29.7 nmol/L) or extremely low (≤16.6 nmol/L) level of serum 25OHD was associated with shorter LTL: 0.018 SD (standardized β = −0.018, 95% CI −0.033 to −0.003, p = 0.022) and 0.048 SD (standardized β = −0.048, 95% CI −0.083 to −0.014, p = 0.006), respectively. Additionally, the high serum 25OHD groups (>95.9 nmol/L) had 0.038 SD (standardized β = −0.038, 95% CI −0.072 to −0.004, p = 0.030) shorter mean LTL than the group with medium 25OHD levels. The associations above were adjusted for multiple variables. Conclusions: In this population-based study, we identified an inverted U-shape relationship between LTL and vitamin D status. Our findings could be affected by unmeasured confounders. Whether high or low vitamin D-associated shorter LTL is mechanistically related to age-related conditions remains to be elucidated.
The Effect of Potassium Nitrate Supplementation on the Force and Properties of Extensor digitorum longus (EDL) Muscles in Mice
Authors: Liubertas Tomas , Poderys Jonas Liudas , Zigmantaite Vilma , Viskelis Pranas , Kucinskas Audrius , Grigaleviciute Ramune , Jurevicius Jonas , Urbonaviciene Dalia
Published: March 2023

Adding potassium nitrate (KNO3) to the diet improves the physiological properties of mammalian muscles (rebuilds weakened muscle, improves structure and functionality). The aim of this study was to investigate the effect of KNO3 supplementation in a mouse model. BALB/c mice were fed a KNO3 diet for three weeks, followed by a normal diet without nitrates. After the feeding period, the Extensor digitorum longus (EDL) muscle was evaluated ex vivo for contraction force and fatigue. To evaluate the possible pathological changes, the histology of EDL tissues was performed in control and KNO3-fed groups after 21 days. The histological analysis showed an absence of negative effects in EDL muscles. We also analyzed 15 biochemical blood parameters. After 21 days of KNO3 supplementation, the EDL mass was, on average, 13% larger in the experimental group compared to the controls (p < 0.05). The muscle-specific force increased by 38% in comparison with the control group (p < 0.05). The results indicate that KNO3 has effects in an experimental mouse model, showing nitrate-diet-induced muscle strength. This study contributes to a better understanding of the molecular changes in muscles following nutritional intervention and may help develop strategies and products designated to treat muscle-related issues.
Oral Toxicities in Cancer Patients, Who Receive Immunotherapy: A Case Series of 24 Patients
Authors: Nicolatou-Galitis Ourania , Psyrri Amanda , Tsoukalas Nikolaos , Galitis Evangelos , Linardou Helena , Galiti Dimitra , Athansiadis Ilias , Kalapanida Despoina , Razis Evangelia , Katirtzoglou Nikolaos , Kentepozidis Nikolaos , Kosmidis Paraskevas , Stavridi Flora , Kyrodimos Efthimios , Daliani Danai , Tsironis George , Mountzios Giannis , Karageorgopoulou Sofia , Gouveris Panagiotis , Syrigos Konstantinos
Published: March 2023

The oral problems of 24 cancer patients on immunotherapy between 2017–2022 and referred by their oncologists, were reported. The age range was 49–80 years, and the median was 64 years. Lung cancer was the most common disease. Three patients a had history of autoimmune disease prior to cancer diagnosis. Patients received immunotherapy for two to 48 months. Prior to immunotherapy, 17 patients received cytotoxic chemotherapy, five angiogenesis inhibitors and one1 radiotherapy to head/neck. During immunotherapy, four patients received chemotherapy, one received bevacizumab, and eight received bone targeting agents, either alone or in combination. Presenting symptoms were oral pain (18 patients, 75%), dental pain (five patients), xerostomia (five patients), burning/itching (seven patients), bleeding (three patients), swelling (three patients), and taste problems (dysgeusia) (three patients). One patient was asymptomatic. Immune-related lesions were observed in 15 patients (62.50%), of which three were exacerbations of prior autoimmune disease. Three patients reported severe deterioration and itching after using a mouthwash. We also observed six (25%) infections (four candidiasis and two herpes simplex), and six (25.00%) cases of medication-related osteonecrosis of the jaw (MRONJ). Five of those MRONJ cases developed among the eight patients with the administration of bone targeting agents and one in a patient with bevacizumab. Two patients presented with more than one lesion. In conclusion, immune-related lesions were most common; oral infections and MRONJ were also observed. Various oral complications might be related to the interplay between immunotherapy and other therapies prior or concurrent to immunotherapy.
Co-Developing Patient-Centered Information: A Focus Group Study of Asthma Patients’ Preferences and Attitudes towards New Medical Treatment Guidelines
Authors: Holst Sara Sommer , Vermehren Charlotte
Published: March 2023

Studies have suggested patient involvement as an important factor when seeking to improve patient-centered information. The objective of this study was to explore asthma patients’ preferences regarding information when co-developing patient-centered information and how they evaluate the material as a supportive initiative when they are deciding whether to switch to the new MART approach. The study was performed as a case study involving qualitative semi-structured focus group interviews inspired by the theoretical framework for supporting patient involvement in research. Two focus group interviews were held, with a total of nine interviewees. Three main interview themes were found: the identification of important topics about the new MART approach, feedback on the design and the preferred implementation of written patient-centered information. The asthma patients preferred written patient-centered material to be short and to be presented briefly at the local community pharmacy, and then discussed more thoroughly with their general practitioner (GP) at a consultation. In conclusion, this study identified asthma patients’ preferences when co-developing written patient-centered information and how the patients favored the material to be implemented as a support to them in their decision on whether to change asthma treatment.
Absolute Risk Reductions in COVID-19 Antiviral Medication Clinical Trials
Authors: Brown Ronald
Published: March 2023

COVID-19 antiviral medications approved or authorized for emergency use by the U.S. Food and Drug Administration are reported to have high efficacy in preventing severe illness, hospitalizations, and deaths. However, reports for some of these antivirals use relative risk reductions from clinical trials without absolute risk reductions. The present paper reappraises recently published clinical trial data for the COVID-19 antivirals paxlovid, remdesivir, and molnupiravir, and reports absolute risk reductions, relative risk reductions, as well as number needed to treat to reduce severe illness, hospitalizations, and deaths. Relative risk reductions are 88.88% for paxlovid (95% CI: 72.13–95.56%), 86.48% for remdesivir (95% CI: 41.41–96.88%), and 30.41% for molnupiravir (95% CI: 0.81–51.18%), while absolute risk reductions are much lower at 5.73% for paxlovid (95% CI: 3.79–7.68%), 4.58% for remdesivir (95% CI: 1.79–7.38%), and 2.96% for molnupiravir (95% CI: 0.09–5.83%). Low absolute risk reductions and the high number of patients needed to treat to reduce severe COVID-19 infections, hospitalizations, and deaths challenge the clinical efficacy of antivirals approved or authorized by the U.S Food and Drug Administration. These findings apply to other populations with similar control event rates. Accurate information should be disseminated to the public when selecting treatments for COVID-19.
Performance Analysis of LDPC-Coded OFDM in Underwater Wireless Optical Communications
Authors: Guo Jianzhong , Xiao Jinpeng , Chen Jing , Shan Xin , Kong Dejin , Wu Yan , Ai Yong
Published: March 2023

The performance of Low-Density Parity-Check (LDPC)-coded Orthogonal Frequency Division Multiplexing (OFDM) is investigated over turbulence channels in underwater wireless optical communications (UWOC). The relation between the bit error ratio (BER) and parameters such as the scintillation coefficient, signal-to-noise ratio (SNR), length of LDPC code, and order of OFDM is quantified by simulation. Results show that while the OFDM with subcarrier quadrature amplitude modulation (QAM-OFDM) has slightly better anti-turbulence performance than the OFDM with subcarrier phase shift keying modulation (PSK-OFDM), the LDPC-coded QAM-OFDM has a much better performance than the QAM-OFDM and the LDPC-coded PSK-OFDM, and, at SNR = 12, it decreases the BER by four orders of magnitude compared to the 16QAM-OFDM system when the scintillation coefficient σξ2 = 0.05.