bluuebunny/crossref_metadata_2025 huggingface dataset:
Racing Performance of the Quarter Horse: Genetic Parameters, Trends and Correlation for Earnings, Best Time and Time Class
Authors: Faria Ricardo , Vicente António , Silva Josineudson
Published: June 2023

The aim of this study was to evaluate the sprint racing performance of Quarter Horses in Brazil. Estimating genetic parameters, trends and correlations were obtained by single- and two-trait analyses using Bayesian inference (earnings to 2 years of equestrian age, best time and time class at distances of 301 m and 402 m). The data comprised a period of 38 equestrian years (1978 to 2015) with 23,482 sprint race records from 5861 animals. The heritability estimates were of low to moderate magnitude, ranging from 0.10 to 0.37 (single-trait) and from 0.15 to 0.41 (two-traits), and the repeatability was 0.31 to 0.46. The additive, residual and phenotypic correlations between earnings to 2 years of equestrian age and the other traits (best time and time class in distances 301 m and 402 m) were high (−0.95, −0.96, 0.69 and 0.92), low (−0.29, −0.37, 0.26 and 0.27) and moderate (−0.41, −0.47, 0.37 and 0.47), respectively. There is a positive genetic trend for all traits considered. However, evaluation of the last 10 equestrian years (2006 to 2015) showed negative trends (genetic loss) and trends close to zero (genetic stagnation). The design of breeding programs using the earnings trait in conjunction with other racing performance traits can enhance changes in the genetic gains as a whole in speed-racing Quarter Horses. These findings suggest that the traits studied should be included in breeding selection programs for racing Quarter Horses.
Goat Pleomorphic Adenoma Gene 1 (PLAG1): mRNA Expression, CNV Detection and Associations with Growth Traits
Authors: Wang Qian , Wei Zhenyu , Zhu Haijing , Pan Chuanying , Akhatayeva Zhanerke , Song Xiaoyue , Lan Xianyong
Published: June 2023

The pleomorphic adenoma gene 1 (PLAG1) gene, as the major gene responsible for growth, plays a vital role in myogenesis. Meanwhile, the relationship between copy number variation (CNV) of this gene and growth traits in goats remains unclear. Therefore, this study investigated four aspects: bioinformatics analysis, mRNA expression (n = 6), CNV detection (n = 224), and association analysis. The findings indicated that the gene had a large number of conserved motifs, and the gene expression level was higher in fetal goats than in adult goats. Three CNV loci were selected from the database, among which CNV1 was located in the bidirectional promoter region and was associated with goat growth traits. CNV analysis showed that CNV2 and CNV3 of the PLAG1 gene were associated with growth traits such as body weight, heart girth, height at hip cross, and hip width (p < 0.05), with CNV1 loss genotype being the superior genotype, and CNV2 and CNV3 median and gain genotypes of being superior genotypes. This finding further confirms that the PLAG1 gene is the dominant gene for growth traits, which will serve as theoretical guidance for goat breeding.
Increased Effect of Foot-and-Mouth Disease Virus Vaccine Structural Protein Antibody Positivity Rates in Piglets Orally Treated with Amino–Zinc Complex
Authors: Lee Byoung-Ryol , Lee Hu-Jang , Kim Nam-Hoon , Kim Yong-Sik , Park Kwang Il
Published: June 2023

Foot-and-mouth disease (FMD) is a highly contagious animal disease that occurs in cloven-hoofed animals including pigs. To prevent FMD, vaccines and adjuvants are routinely used to induce an immune response; however, it requires an extended period of time to produce sufficient antibodies to prevent viral infection. In this study, we evaluated the increased effectiveness of the FMD vaccine structural protein (SP) antibody by administrating the Amino–Zn adjuvant to 100 pigs from 3 test pig farms in their feed. The FMD vaccine antibody titer and immunological index were analyzed using an enzyme-linked immunosorbent assay (ELISA) kit, and the hematological and blood biochemical parameters were analyzed using an automatic blood analyzer. The titer of the FMD vaccine SP antibodies in the 0.2% Amino–Zn-administered group was significantly increased compared to that of the positive control group only injected with FMD vaccine at 4 weeks after the first vaccination and at 4, 8, and 16 weeks after the second vaccination (p < 0.05). The FMD vaccine SP antibody positive rate was 100% until shipment. The IFN-γ and IgA levels were significantly increased by Amino–Zn administration 4 weeks after the first vaccination and 4 weeks after the second vaccination (p < 0.05). On the other hand, serum AST, and CPK (p < 0.001) were significantly decreased by Amino–Zn administration. These results show that the administration of Amino–Zn is effective in enhancing the antibody titer and immunogenicity of the FMD vaccine and can be used as an oral adjuvant (OrAd) to prevent viral diseases, such as FMD.
The Effect of Radial Extracorporeal Shock Wave Therapy (rESWT) on the Skin Surface Temperature of the Longissimus Dorsi Muscle in Clinically Healthy Racing Thoroughbreds: A Preliminary Study
Authors: Śniegucka Karolina , Soroko-Dubrovina Maria , Zielińska Paulina , Dudek Krzysztof , Žuffová Kristína
Published: June 2023

Radial extracorporeal shock wave therapy (rESWT) is increasingly being used to treat musculoskeletal injuries in horses. The aim of this study was to assess the influence of rESWT on the skin surface temperature of the longissimus dorsi muscle in clinically healthy racing horses. A total of 24 thoroughbreds were divided into a study group (n = 12) and an rESWT-sham group (n = 12). The study group underwent rESWT, whereas the rESWT-sham group had rESWT without probe activation in the treated area. Both groups underwent thermographic examination before and just after rESWT to determine and compare skin surface temperatures. Palpation examination was performed after the first and second thermography examination to assess longissimus dorsi muscle tone. Additionally, thermographic examination was repeated 10 min after the rESWT. In both groups, there was an increase in skin surface temperature just after rESWT, and a decrease 10 min after it to below the initial value. In the study group, the skin surface temperature just after rESWT was higher than in the rESWT-sham group. Additionally, in the study group the average muscle tone before rESWT was significantly higher than just after the procedure, whereas in the rESWT-sham group the average change in muscle tone was not significant. The results proved that rESWT increases skin surface temperature of the longissimus dorsi muscle in clinically healthy horses. Further research is necessary in order to configure shockwave treatment with appropriate parameters for effective and safe therapy.
Human–Animal Interactions in Dairy Goats
Authors: Carnovale Francesca , Marcone Giovanni , Serrapica Francesco , Lambiase Claudia , Sabia Emilio , Arney David , De Rosa Giuseppe
Published: June 2023

It is widely assumed that the quality of human–animal interactions may have a strong impact on animals’ living conditions and is fundamental to improving farm animal welfare. This work aims to evaluate the effectiveness of methods for assessing and monitoring the welfare of lactating goats. In particular, attention was paid to the methods regarding the assessment of the human–animal relationship. The experimental protocol included three tests and observations in the milking parlour, namely: avoidance distance in the pen, avoidance distance at the manger, approach test within 2 min and behavioural observations of stockmen and animals during milking. Fourteen dairy goat farms located in the province of Potenza (Southern Italy) with flocks ranging in size from 67 to 450 lactating goats were used. All farms raised the Rossa Mediterranean goat breed. The percentage of goats that permitted themselves to be touched at the manger (mean ± SD: 12.36 ± 9.50) was higher than that found in the pen (9.67 ± 11.86) and within 2 min inside the pen (8.19 ± 13.78). The avoidance distance at the manger (0.63 ± 0.28 m) was shorter than that recorded in the pen (1.19 ± 0.58 m). Avoidance distance at the manger was positively correlated with that in the pen (Spearman correlation test (rs) = 0.607; p < 0.01), as was the percentage of goats touched at the manger and in the pen (rs = 0.647; p < 0.01). Approximately 60% of the stockman interactions observed during milking were neutral, while positive and negative interactions had similar values to each other, approximately 20%. The number of neutral stockman interactions was positively correlated with the percentage of goats moving when approached at a distance >1 m (rs = 0.799; p < 0.001) and was negatively correlated with the animals touched at the manger (rs = −0.607; p < 0.05), in the pen (rs = −0.613; p < 0.05) and within 2 min (rs = −0.669; p < 0.01). As regards the degree of association between the behaviour of the milker and the animals during the milking routine, the percentage of neutral interactions tended to be positively correlated only with the number of kicks performed by the animals (rs = 0.476; p < 0.10). It is concluded that avoidance distance at the manger and in the pen, as for other farm animals, are valid tests to evaluate the human–animal relationship in goats. In addition, avoidance distance at the manger may reliably replace the test performed in the pen.
Using Targeted Nano-Antibiotics to Improve Antibiotic Efficacy against Staphylococcus aureus Infections
Authors: Le Hung , Dé Emmanuelle , Le Cerf Didier , Karakasyan Carole
Published: June 2023

The poor bioavailability of antibiotics at infection sites is one of the leading causes of treatment failure and increased bacterial resistance. Therefore, developing novel, non-conventional antibiotic delivery strategies to deal with bacterial pathogens is essential. Here, we investigated the encapsulation of two fluoroquinolones, ciprofloxacin and levofloxacin, into polymer-based nano-carriers (nano-antibiotics), with the goal of increasing their local bioavailability at bacterial infection sites. The formulations were optimized to achieve maximal drug loading. The surfaces of nano-antibiotics were modified with anti-staphylococcal antibodies as ligand molecules to target S. aureus pathogens. The interaction of nano-antibiotics with the bacterial cells was investigated via fluorescent confocal microscopy. Conventional tests (MIC and MBC) were used to examine the antibacterial properties of nano-antibiotic formulations. Simultaneously, a bioluminescence assay model was employed, revealing the rapid and efficient assessment of the antibacterial potency of colloidal systems. In comparison to the free-form antibiotic, the targeted nano-antibiotic exhibited enhanced antimicrobial activity against both the planktonic and biofilm forms of S. aureus. Furthermore, our data suggested that the efficacy of a targeted nano-antibiotic treatment can be influenced by its antibiotic release profile.
Improvement of Fresh Ovine “Tuma” Cheese Quality Characteristics by Application of Oregano Essential Oils
Authors: Garofalo Giuliana , Ponte Marialetizia , Greco Carlo , Barbera Marcella , Mammano Michele Massimo , Fascella Giancarlo , Greco Giuseppe , Salsi Giulia , Orlando Santo , Alfonzo Antonio , Di Grigoli Antonino , Piazzese Daniela , Bonanno Adriana , Settanni Luca , Gaglio Raimondo
Published: June 2023

In the present work, oregano essential oils (OEOs) were applied to process the fresh ovine cheese “Tuma” obtained by pressed cheese technology. Cheese making trials were performed under industrial conditions using ewe’s pasteurized milk and two strains of Lactococcus lactis (NT1 and NT4) as fermenting agents. Two experimental cheese products (ECP) were obtained through the addition of 100 (ECP100) and 200 (ECP200) µL/L of OEO to milk, while the control cheese product (CCP) was OEO-free. Both Lc. lactis strains showed in vitro and in vivo ability to grow in the presence of OEOs and to dominate over indigenous milk lactic acid bacteria (LAB) resistant to pasteurization. In the presence of OEOs, the most abundant compound found in cheese was carvacrol, constituting more than 65% of the volatile fraction in both experimental products. The addition of OEOs did not influence ash, fat, or protein content, but it increased by 43% the antioxidant capacity of the experimental cheeses. ECP100 cheeses showed the best appreciation scores by the sensory panel. In order to investigate the ability OEOs to be used as a natural preservative, a test of artificial contamination was carried out, and the results showed a significant reduction of the main dairy pathogens in OEO-added cheeses.
The Influence of Antioxidants on Oxidative Stress-Induced Vascular Aging in Obesity
Authors: Sharebiani Hiva , Keramat Shayan , Chavoshan Abdolali , Fazeli Bahar , Stanek Agata
Published: June 2023

Obesity is a worldwide trend that is growing in incidence very fast. Adipose tissue dysfunction caused by obesity is associated with the generation of oxidative stress. Obesity-induced oxidative stress and inflammation play a key role in the pathogenesis of vascular diseases. Vascular aging is one of the main pathogenesis mechanisms. The aim of this study is to review the effect of antioxidants on vascular aging caused by oxidative stress in obesity. In order to achieve this aim, this paper is designed to review obesity-caused adipose tissue remodeling, vascular aging generated by high levels of oxidative stress, and the effects of antioxidants on obesity, redox balance, and vascular aging. It seems that vascular diseases in obese individuals are complex networks of pathological mechanisms. In order to develop a proper therapeutic tool, first, there is a need for a better understanding of interactions between obesity, oxidative stress, and aging. Based on these interactions, this review suggests different lines of strategies that include change in lifestyle to prevent and control obesity, strategies for adipose tissue remodelling, oxidant–antioxidant balance, inflammation suppression, and strategies against vascular aging. Some antioxidants support different lines of these strategies, making them appropriate for complex conditions such as oxidative stress-induced vascular diseases in obese individuals.
Epoxy Resin-Reinforced F-Assisted Na3Zr2Si2PO12 Solid Electrolyte for Solid-State Sodium Metal Batteries
Authors: Fu Yao , Liu Dangling , Sun Yongjiang , Zhao Genfu , Guo Hong
Published: June 2023

Solid sodium ion batteries (SIBs) show a significant amount of potential for development as energy storage systems; therefore, there is an urgent need to explore an efficient solid electrolyte for SIBs. Na3Zr2Si2PO12 (NZSP) is regarded as one of the most potential solid-state electrolytes (SSE) for SIBs, with good thermal stability and mechanical properties. However, NZSP has low room temperature ionic conductivity and large interfacial impedance. F−doped NZSP has a larger grain size and density, which is beneficial for acquiring higher ionic conductivity, and the composite system prepared with epoxy can further improve density and inhibit Na dendrite growth. The composite system exhibits an outstanding Na+ conductivity of 0.67 mS cm−1 at room temperature and an ionic mobility number of 0.79. It also has a wider electrochemical stability window and cycling stability.
Infrared Thermography Imaging for Assessment of Peripheral Perfusion in Patients with Septic Shock
Authors: Kazune Sigita , Vasiljevs Edgars , Caica-Rinca Anastasija , Marcinkevics Zbignevs , Grabovskis Andris
Published: June 2023

Skin temperature changes can be used to assess peripheral perfusion in circulatory shock patients. However, research has been limited to point measurements from acral parts of the body. Infrared thermography allows non-invasive evaluation of temperature distribution over a larger surface. Our study aimed to map thermographic patterns in the knee and upper thigh of 81 septic shock patients within 24 h of admission and determine the relationship between skin temperature patterns, mottling, and 28-day mortality. We extracted skin temperature measurements from zones corresponding to mottling scores and used a linear mixed model to analyze the distribution of skin temperature in patients with different mottling scores. Our results showed that the distribution of skin temperature in the anterior thigh and knee is physiologically heterogeneous and has no significant association with mottling or survival at 28 days. However, overall skin temperature of the anterior thigh and knee is significantly lower in non-survivors when modified by mottling score. No differences were found in skin temperature between the survivor and non-survivor groups. Our study shows the potential usefulness of infrared thermography in evaluating skin temperature patterns in resuscitated septic shock patients. Overall skin temperature of the anterior thigh and knee may be an important indicator of survival status when modified by mottling score.
Multimodal Deep Learning for Predicting Adverse Birth Outcomes Based on Early Labour Data
Authors: Asfaw Daniel , Jordanov Ivan , Impey Lawrence , Namburete Ana , Lee Raymond , Georgieva Antoniya
Published: June 2023

Cardiotocography (CTG) is a widely used technique to monitor fetal heart rate (FHR) during labour and assess the health of the baby. However, visual interpretation of CTG signals is subjective and prone to error. Automated methods that mimic clinical guidelines have been developed, but they failed to improve detection of abnormal traces. This study aims to classify CTGs with and without severe compromise at birth using routinely collected CTGs from 51,449 births at term from the first 20 min of FHR recordings. Three 1D-CNN and LSTM based architectures are compared. We also transform the FHR signal into 2D images using time-frequency representation with a spectrogram and scalogram analysis, and subsequently, the 2D images are analysed using a 2D-CNNs. In the proposed multi-modal architecture, the 2D-CNN and the 1D-CNN-LSTM are connected in parallel. The models are evaluated in terms of partial area under the curve (PAUC) between 0–10% false-positive rate; and sensitivity at 95% specificity. The 1D-CNN-LSTM parallel architecture outperformed the other models, achieving a PAUC of 0.20 and sensitivity of 20% at 95% specificity. Our future work will focus on improving the classification performance by employing a larger dataset, analysing longer FHR traces, and incorporating clinical risk factors.
Bioactive Restorative Materials Applied over Coronal Dentine—A Bibliometric and Critical Review
Authors: Pires Paula Maciel , Rosa Thamirys da Costa , Ribeiro-Lages Mariana Batista , Duarte Maysa Lannes , Cople Maia Lucianne , Neves Aline de Almeida , Sauro Salvatore
Published: June 2023

The objective of the research was to examine the scientific literature concerning restorative materials with bioactive properties for the purpose of covering dentin. Searches were performed in various databases including MEDLINE, Scopus, Web of Science, Cochrane Library, Lilacs/BBO, and Embase. Inclusion criteria involved studies that utilized the terms “dentin” and “bioactive”, along with “ion-releasing”, “smart materials”, “biomimetic materials” and “smart replacement for dentin”. The information extracted included the title, authors, publication year, journal and the country of affiliation of the corresponding author. The studies were categorized based on their study design, type of material, substrate, analytical method, and bioactivity. A total of 7161 records were recovered and 159 were included for data extraction. Most of the publications were in vitro studies (n = 149), testing different types of materials in sound dentine (n = 115). Most studies were published in Dental Materials (n = 29), and an increase in publications could be observed after the year 2000. Most of the articles were from the USA (n = 34), followed by Brazil (n = 28). Interfacial analysis was the most investigated (n = 105), followed by bond strength (n = 86). Bioactivity potential was demonstrated for most tested materials (n = 148). This review presents insights into the current trends of bioactive materials development, clearly showing a severe lack of clinical studies.
Recent Advances in Metal–Organic Frameworks (MOFs) and Their Composites for Non-Enzymatic Electrochemical Glucose Sensors
Authors: Li Panpan , Peng Yi , Cai Jinpeng , Bai Yang , Li Qing , Pang Huan
Published: June 2023

In recent years, with pressing needs such as diabetes management, the detection of glucose in various substrates has attracted unprecedented interest from researchers in academia and industry. As a relatively new glucose sensor, non-enzymatic target detection has the characteristics of high sensitivity, good stability and simple manufacturing process. However, it is urgent to explore novel materials with low cost, high stability and excellent performance to modify electrodes. Metal–organic frameworks (MOFs) and their composites have the advantages of large surface area, high porosity and high catalytic efficiency, which can be utilized as excellent materials for electrode modification of non-enzymatic electrochemical glucose sensors. However, MOFs and their composites still face various challenges and difficulties that limit their further commercialization. This review introduces the applications and the challenges of MOFs and their composites in non-enzymatic electrochemical glucose sensors. Finally, an outlook on the development of MOFs and their composites is also presented.
Contractile Work of the Soleus and Biarticular Mechanisms of the Gastrocnemii Muscles Increase the Net Ankle Mechanical Work at High Walking Speeds
Authors: Kharazi Mohamadreza , Theodorakis Christos , Mersmann Falk , Bohm Sebastian , Arampatzis Adamantios
Published: June 2023

Increasing walking speed is accompanied by an increase of the mechanical power and work performed at the ankle joint despite the decrease of the intrinsic muscle force potential of the soleus (Sol) and gastrocnemius medialis (GM) muscles. In the present study, we measured Achilles tendon (AT) elongation and, based on an experimentally determined AT force–elongation relationship, quantified AT force at four walking speeds (slow 0.7 m.s−1, preferred 1.4 m.s−1, transition 2.0 m.s−1, and maximum 2.6 ± 0.3 m.s−1). Further, we investigated the mechanical power and work of the AT force at the ankle joint and, separately, the mechanical power and work of the monoarticular Sol at the ankle joint and the biarticular gastrocnemii at the ankle and knee joints. We found a 21% decrease in maximum AT force at the two higher speeds compared to the preferred; however, the net work of the AT force at the ankle joint (ATF work) increased as a function of walking speed. An earlier plantar flexion accompanied by an increased electromyographic activity of the Sol and GM muscles and a knee-to-ankle joint energy transfer via the biarticular gastrocnemii increased the net ATF mechanical work by 1.7 and 2.4-fold in the transition and maximum walking speed, respectively. Our findings provide first-time evidence for a different mechanistic participation of the monoarticular Sol muscle (i.e., increased contractile net work carried out) and the biarticular gastrocnemii (i.e., increased contribution of biarticular mechanisms) to the speed-related increase of net ATF work.
Clinicopathological Outlines of Post-COVID-19 Pulmonary Fibrosis Compared with Idiopathic Pulmonary Fibrosis
Authors: Cîrjaliu Roxana-Elena , Deacu Mariana , Gherghișan Ioana , Marghescu Angela-Ștefania , Enciu Manuela , Băltățescu Gabriela Izabela , Nicolau Antonela Anca , Tofolean Doina-Ecaterina , Arghir Oana Cristina , Fildan Ariadna-Petronela
Published: June 2023

This review brings together the current knowledge regarding the risk factors and the clinical, radiologic, and histological features of both post-COVID-19 pulmonary fibrosis (PCPF) and idiopathic pulmonary fibrosis (IPF), describing the similarities and the disparities between these two diseases, using numerous databases to identify relevant articles published in English through October 2022. This review would help clinicians, pathologists, and researchers make an accurate diagnosis, which can help identify the group of patients selected for anti-fibrotic therapies and future therapeutic perspectives.
Human Regulatory Macrophages Derived from THP-1 Cells Using Arginylglycylaspartic Acid and Vitamin D3
Authors: Pham Hoang Lan , Hoang Thi Xoan , Kim Jae Young
Published: June 2023

Regulatory macrophages (Mregs) are unique in that they have anti-inflammatory and immunosuppressive properties. Thus, treating inflammatory diseases using Mregs is an area of active research. Human Mregs are usually generated by culturing peripheral blood monocytes stimulated using a macrophage colony-stimulating factor with interferon (IFN)-γ. Herein, we generated Mregs with an elongated cell morphology from THP-1 cells that were stimulated with phorbol 12-myristate 13-acetate and cultured with both arginylglycylaspartic acid and vitamin D3. These Mregs regulated macrophage function, and respectively downregulated and upregulated the expression of pro-inflammatory and immunosuppressive mediators. They also expressed Mregs-specific markers, such as dehydrogenase/reductase 9, even when exposed to such inflammatory stimulants as IFN-γ, lipopolysaccharide, purified xenogeneic antigen, and xenogeneic cells. The Mregs also exerted anti-inflammatory and anticoagulatory actions in response to xenogeneic cells, as well as exerting immunosuppressive effects on mitogen-induced Jurkat T-cell proliferation. Our method of generating functional Mregs in vitro without cytokines is simple and cost-effective.
An Uncommon Cause of Recurrent Presyncope, Dizziness, and Tachycardia: A Case Report of Diffuse, Adult-Onset Nesidioblastosis/Non-Insulinoma Pancreatogenous Hypoglycemia Syndrome (NIPHS)
Authors: Dieterle Martin Philipp , Husari Ayman , Prozmann Sophie Nicole , Wiethoff Hendrik , Stenzinger Albrecht , Röhrich Manuel , Pfeiffer Uwe , Kießling Wolfgang Rüdiger , Engel Helena , Sourij Harald , Steinberg Thorsten , Tomakidi Pascal , Kopf Stefan , Szendroedi Julia
Published: June 2023

Neurovegetative and autonomic symptoms are common presentations of various diseases, ranging from psychosomatic to severe organic disorders. A 23-year-old man presented with a history of recurrent presyncope, dizziness, and tachycardia. Repeated diagnostic work-up in various clinical settings could not identify any definite cause for approximately eight years. However, the incidental detection of postprandial and exercise-induced hypoglycemia was suggestive of an insulin-related disorder. A 72 h plasma glucose fasting test revealed endogenous hyperinsulinism. Upon imaging studies, no tumor mass potentially indicating insulinoma could be detected. 68Ga-DOTA-Exendin-4 PET/CT showed diffuse tracer enrichment throughout the whole pancreas. A subtotal pancreatectomy was performed, and the diagnosis of diffuse, adult-onset nesidioblastosis was established histopathologically. This corresponds to the clinical findings of a functional β-cell disorder, also known as non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS). After nine months, the symptoms recurred, making complete pancreatectomy necessary. Postoperative laboratory evaluation exhibited no residual endogenous C-peptide production. This case illustrates the diagnostic challenges in patients presenting with unspecific, neurovegetative and autonomic symptoms with a severe and rare underlying cause.
Mannose-Binding Lectin Reduces Oxidized Low-Density Lipoprotein Induced Vascular Endothelial Cells Injury by Inhibiting LOX1-ox-LDL Binding and Modulating Autophagy
Authors: Zhou Xuelian , Chen Xuefeng , Zhang Li , Yuan Jinna , Lin Hu , Zhu Mingqiang , Xu Xiaoqin , Dong Guanping , Fu Junfen , Wu Wei
Published: June 2023

Objective: To investigate the role of mannose-binding lectin (MBL) in modulating autophagy and protecting endothelial cells (ECs) from oxidized low-density lipoprotein (ox-LDL)-induced injury. Methods: Serum MBL concentration and carotid intima-media thickness (cIMT) were measured in 94 obese and 105 healthy children. ECs were transfected with MBL over-expression plasmid, LOX1 was knocked-down to explore the protective role of MBL in ox-LDL induced ECs injury. Dendritic cells (DCs) were co-cultured with ECs, and inflammatory factors, DC maturation, and autophagy was assessed. WT and ApoE−/− mice were fed with a high fat diet (HFD) with or without MBL-adenovirus injection for 16 weeks and aortic vascular endothelial tissue was isolated, then atherosclerotic plaque, cell injury and autophagy were analyzed. Results: Serum MBL concentration in obese children was lower than healthy controls and was negatively correlated with cIMT. The uptake of ox-LDL was decreased in LOX1 knock-down ECs. MBL over-expression in vitro inhibited LOX1-ox-LDL binding. Both LOX1 knock-down and MBL over-expression can ameliorate EC autophagy and cell injury. MBL over-expression in vivo alleviated atherosclerotic plaque formation, influenced DC maturation and down-regulated IL-6, IL-12, and TNF-a levels. Conclusions: MBL exerts a protective role in ox-LDL-induced EC injury by modulating DC maturation and EC autophagy via inhibiting LOX1-ox-LDL binding.
Carrier-Free Inhalable Dry Microparticles of Celecoxib: Use of the Electrospraying Technique
Authors: Jahangiri Azin , Nokhodchi Ali , Asare-Addo Kofi , Salehzadeh Erfan , Emami Shahram , Yaqoubi Shadi , Hamishehkar Hamed
Published: June 2023

Upregulation of cyclooxygenase (COX-2) plays an important role in lung cancer pathogenesis. Celecoxib (CLX), a selective COX-2 inhibitor, may have beneficial effects in COVID-19-induced inflammatory storms. The current study aimed to develop carrier-free inhalable CLX microparticles by electrospraying as a dry powder formulation for inhalation (DPI). CLX microparticles were prepared through an electrospraying method using a suitable solvent mixture at two different drug concentrations. The obtained powders were characterized in terms of their morphology, solid state, dissolution behavior, and aerosolization performance. Electrosprayed particles obtained from the ethanol–acetone solvent mixture with a drug concentration of 3 % w/v exhibited the best in vitro aerosolization properties. The value of the fine particle fraction obtained for the engineered drug particles was 12-fold higher than that of the untreated CLX. When the concentration of CLX was increased, a remarkable reduction in FPF was obtained. The smallest median mass aerodynamic diameter was obtained from the electrosprayed CLX at a 3% concentration (2.82 µm) compared to 5% (3.25 µm) and untreated CLX (4.18 µm). DSC and FTIR experiments showed no change in drug crystallinity or structure of the prepared powders during the electrospraying process. The findings of this study suggest that electrospraying has potential applications in the preparation of DPI formulations.
Urodynamics Are Essential to Predict the Risk for Upper Urinary Tract Damage after Acute Spinal Cord Injury
Authors: Birkhäuser Veronika , Anderson Collene E. , Kozomara Marko , Bywater Mirjam , Gross Oliver , Kiss Stephan , Knüpfer Stephanie C. , Koschorke Miriam , Leitner Lorenz , Mehnert Ulrich , Sadri Helen , Sammer Ulla , Stächele Lara , Tornic Jure , Liechti Martina D. , Brinkhof Martin W. G. , Kessler Thomas M.
Published: June 2023

We used clinical parameters to develop a prediction model for the occurrence of urodynamic risk factors for upper urinary tract (UUT) damage during the first year after acute spinal cord injury (SCI). A total of 97 patients underwent urodynamic investigation at 1, 3, 6, and 12 months after acute SCI, within the framework of a population-based longitudinal study at a single university SCI center. Candidate predictors included demographic characteristics and neurological and functional statuses 1 month after SCI. Outcomes included urodynamic risk factors for UUT damage: detrusor overactivity combined with detrusor sphincter dyssynergia, maximum storage detrusor pressure (pDetmax) ≥ 40 cmH2O, bladder compliance < 20 mL/cmH2O, and vesicoureteral reflux. Multivariable logistic regression was used for the prediction model development and internal validation, using the area under the receiver operating curve (aROC) to assess model discrimination. Two models showed fair discrimination for pDetmax ≥ 40 cmH2O: (i) upper extremity motor score and sex, aROC 0.79 (95% CI: 0.69–0.89), C-statistic 0.78 (95% CI: 0.69–0.87), and (ii) neurological level, American Spinal Injury Association Impairment Scale grade, and sex, aROC 0.78 (95% CI: 0.68–0.89), C-statistic 0.76 (95% CI: 0.68–0.85). We identified two models that provided fair predictive values for urodynamic risk factors of UUT damage during the first year after SCI. Pending external validation, these models may be useful for clinical trial planning, although less so for individual-level patient management. Therefore, urodynamics remains essential for reliably identifying patients at risk of UUT damage.
Synthesizing Electronic Health Records for Predictive Models in Low-Middle-Income Countries (LMICs)
Authors: Ghosheh Ghadeer O. , Thwaites C. Louise , Zhu Tingting
Published: June 2023

The spread of machine learning models, coupled with by the growing adoption of electronic health records (EHRs), has opened the door for developing clinical decision support systems. However, despite the great promise of machine learning for healthcare in low-middle-income countries (LMICs), many data-specific limitations, such as the small size and irregular sampling, hinder the progress in such applications. Recently, deep generative models have been proposed to generate realistic-looking synthetic data, including EHRs, by learning the underlying data distribution without compromising patient privacy. In this study, we first use a deep generative model to generate synthetic data based on a small dataset (364 patients) from a LMIC setting. Next, we use synthetic data to build models that predict the onset of hospital-acquired infections based on minimal information collected at patient ICU admission. The performance of the diagnostic model trained on the synthetic data outperformed models trained on the original and oversampled data using techniques such as SMOTE. We also experiment with varying the size of the synthetic data and observe the impact on the performance and interpretability of the models. Our results show the promise of using deep generative models in enabling healthcare data owners to develop and validate models that serve their needs and applications, despite limitations in dataset size.
Effects of the Co-Overexpression of the BCL and BDNF Genes on the Gamma-Aminobutyric Acid-Ergic Differentiation of Wharton’s-Jelly-Derived Mesenchymal Stem Cells
Authors: Borkowska Paulina , Morys Julia , Zielinska Aleksandra , Kowalski Jan
Published: June 2023

One of the problems with using MSCs (mesenchymal stem cells) to treat different neurodegenerative diseases of the central nervous system is their low ability to spontaneously differentiate into functional neurons. The aim of this study was to investigate how the co-overexpression of the BCL and BDNF genes affects the ability of genetically modified MSCs to differentiate into GABA-ergic neurons. A co-overexpression of two genes was performed, one of which, BCL, was supposed to increase the resistance of the cells to the toxic agents in the brain environment. The second one, BDNF, was supposed to direct the cells onto the neuronal differentiation pathway. As a result, the co-overexpression of both BCL2 + BDNF and BCLXL + BDNF caused an increase in the MAP2 gene expression level (a marker of the neuronal pathway) and the SYP gene that is associated with synaptogenesis. In both cases, approximately 18% of the genetically modified and then differentiated cells exhibited the presence of the GAD protein, which is characteristic of GABA-ergic neurons. Despite the presence of GAD, after both modifications, only the BCL2 and BDNF co-overexpression correlated with the ability of the modified cells to release gamma-aminobutyric acid (GABA) after depolarization. Our study identified a novel model of genetically engineered MSCs that can be used as a tool to deliver the antiapoptotic proteins (BCL) and neurotrophic factor (BDNF) directly into the brain microenvironment. Additionally, in the investigated model, the genetically modified MSCs could easily differentiate into functional GABA-ergic neurons and, moreover, due to the secreted BCL and BDNF, promote endogenous neuronal growth and encourage synaptic connections between neurons.
Biomimetics with Trade-Offs
Authors: Vincent Julian
Published: June 2023

Our knowledge of physics and chemistry is relatively well defined. Results from that knowledge are predictable as, largely, are those of their technical offspring such as electrical, chemical, mechanical and civil engineering. By contrast, biology is relatively unconstrained and unpredictable. A factor common to all areas is the trade-off, which provides a means of defining and quantifying a problem and, ideally, its solution. In order to understand the anatomy of the trade-off and how to handle it, its development (as the dialectic) is tracked from Hegel and Marx to its implementation as dialectical materialism in Russian philosophy and TRIZ, the Theory of Invention. With the ready availability of mathematical techniques, such as multi-objective analysis and the Pareto set, the trade-off is well-adapted to bridging the gaps between the quantified and the unquantifiable, allowing modelling and the transfer of concepts by analogy. It is thus an ideal tool for biomimetics. An intracranial endoscope can be derived with little change from the egg-laying tube of a wood wasp. More complex transfers become available as the technique is developed. Most important, as more trade-offs are analyzed, their results are stored to be used again in the solution of problems. There is no other system in biomimetics which can do this.
Binary Restructuring Particle Swarm Optimization and Its Application
Authors: Zhu Jian , Liu Jianhua , Chen Yuxiang , Xue Xingsi , Sun Shuihua
Published: June 2023

Restructuring Particle Swarm Optimization (RPSO) algorithm has been developed as an intelligent approach based on the linear system theory of particle swarm optimization (PSO). It streamlines the flow of the PSO algorithm, specifically targeting continuous optimization problems. In order to adapt RPSO for solving discrete optimization problems, this paper proposes the binary Restructuring Particle Swarm Optimization (BRPSO) algorithm. Unlike other binary metaheuristic algorithms, BRPSO does not utilize the transfer function. The particle updating process in BRPSO relies solely on comparison results between values derived from the position updating formula and a random number. Additionally, a novel perturbation term is incorporated into the position updating formula of BRPSO. Notably, BRPSO requires fewer parameters and exhibits high exploration capability during the early stages. To evaluate the efficacy of BRPSO, comprehensive experiments are conducted by comparing it against four peer algorithms in the context of feature selection problems. The experimental results highlight the competitive nature of BRPSO in terms of both classification accuracy and the number of selected features.
Mediating Effect of Quality of Sleep Moderated by Meaning in Life on the Relationship between Hwabyung and Suicidal Ideation in Middle-Aged Korean Women
Authors: Jeong Goo-Churl , An Jae-Sun , Shin Sun-Hwa
Published: June 2023

The purpose of this study was to determine the role of the quality of sleep and meaning in life in the process by which Hwabyung symptoms affect suicidal ideation in middle-aged Korean women. A total of 265 women aged 40–65 years were enrolled in an online survey. The study variables were measured using the Hwabyung, quality of sleep, meaning in life, and suicidal ideation scales. The data were analyzed using the PROCESS Procedure for SPSS Release 3.5 (Model 14) program with a 95% bias-corrected bootstrap confidence interval. Hwabyung symptoms in middle-aged women had a significant direct effect on suicidal ideation, and an indirect effect through the quality of sleep was also statistically significant. Meaning in life was found to significantly moderate the indirect effect of Hwabyung on suicidal ideation through the quality of sleep. In other words, the greater the meaning in life, the weaker the effect of Hwabyung on suicidal ideation through the quality of sleep. The Hwabyung of middle-aged women caused a psychological crisis and was a great threat to physical health by lowering the quality of sleep. The low quality of sleep and the increase in suicidal ideation due to Hwabyung pose a great threat to the survival of middle-aged women. It was found that it is very important to find meaning in one’s life as an effective way to reduce suicidal ideation in middle-aged women.
The Role of Emergent Literacy Assessment in Brazilian Portuguese Literacy Acquisition during COVID-19
Authors: Borges Érica Prates Krás , Koltermann Gabriella , Minervino Carla Alexandra da Silva Moita , de Salles Jerusa Fumagalli
Published: June 2023

The contributions of emergent literacy skills to reading and writing development have been evidenced in different linguistic contexts. The worsening of the Brazil literacy scenario during the pandemic denoted the importance of a better understanding of these contributions’ specificities in Brazilian Portuguese to support evidence-based mitigation strategies. This study aimed to analyze the associations between emergent literacy components (emergent writing, alphabet knowledge, vocabulary, and phonological awareness) and word/pseudoword reading and spelling performance in first grade students during COVID-19. A total of 42 children (Mage = 6.29 years, SD = 0.45, 52.4% female) participated remotely in this study. Correlations and multilinear regression analyses were conducted. The results show significant associations between emergent literacy components and reading and spelling performance. Stronger associations were found with specific emergent skills such as letter writing, spontaneous writing, letter-sound production, and alliteration. Regression models indicated that children’s performance in early literacy skills explained 49% of the variance in reading and 55% of the variance in spelling. This study highlighted the role of emergent writing and alphabet knowledge as reading and spelling predictors during literacy acquisition in Brazilian Portuguese. Implications for educational context and directions for remediating the negative impact of the pandemic on learning were discussed.
Optimizing Truss Structures Using Composite Materials under Natural Frequency Constraints with a New Hybrid Algorithm Based on Cuckoo Search and Stochastic Paint Optimizer (CSSPO)
Authors: Khodadadi Nima , Harati Ehsan , De Caso Francisco , Nanni Antonio
Published: June 2023

This article highlights the absence of published paradigms hybridized by The Cuckoo Search (CS) and Stochastic Paint Optimizer (SPO) for optimizing truss structures using composite materials under natural frequency constraints. The article proposes a novel optimization algorithm called CSSPO for optimizing truss structures made of composite materials, known as fiber-reinforced polymer (FRP) composites, to address this gap. Optimization problems of truss structures under frequency constraints are recognized as challenging due to their non-linear and non-convex search spaces that contain numerous local optima. The proposed methodology produces high-quality optimal solutions with less computational effort than the original methods. The aim of this work is to compare the performance of carbon FRP (CFRP), glass FRP (GFRP), and steel using a novel hybrid algorithm to provide valuable insights and inform decision-making processes in material selection and design. Four benchmark structure trusses with natural frequency constraints were utilized to demonstrate the efficiency and robustness of the CSSPO. The numerical analysis findings indicate that the CSSPO outperforms the classical SPO and exhibits comparable or superior performance when compared to the SPO. The study highlights that implementing CFRP and GFRP composites in truss construction leads to a notable reduction in weight compared to using steel.
New Approaches to Targeted Therapy in Melanoma
Authors: Fernandez Manuel Felipe , Choi Jacob , Sosman Jeffrey
Published: June 2023

It was just slightly more than a decade ago when metastatic melanoma carried a dismal prognosis with few, if any, effective therapies. Since then, the evolution of cancer immunotherapy has led to new and effective treatment approaches for melanoma. However, despite these advances, a sizable portion of patients with advanced melanoma have de novo or acquired resistance to immune checkpoint inhibitors. At the same time, therapies (BRAF plus MEK inhibitors) targeting the BRAFV600 mutations found in 40–50% of cutaneous melanomas have also been critical for optimizing management and improving patient outcomes. Even though immunotherapy has been established as the initial therapy in most patients with cutaneous melanoma, subsequent effective therapy is limited to BRAFV600 melanoma. For all other melanoma patients, driver mutations have not been effectively targeted. Numerous efforts are underway to target melanomas with NRAS mutations, NF-1 LOF mutations, and other genetic alterations leading to activation of the MAP kinase pathway. In this era of personalized medicine, we will review the current genetic landscape, molecular classifications, emerging drug targets, and the potential for combination therapies for non-BRAFV600 melanoma.
Induction of Senescence by Loss of Gata4 in Cardiac Fibroblasts
Authors: Zhang Zhentao , Shayani Gabriella , Xu Yanping , Kim Ashley , Hong Yurim , Feng Haiyue , Zhu Hua
Published: June 2023

Cardiac fibroblasts are a major source of cardiac fibrosis during heart repair processes in various heart diseases. Although it has been shown that cardiac fibroblasts become senescent in response to heart injury, it is unknown how the senescence of cardiac fibroblasts is regulated in vivo. Gata4, a cardiogenic transcription factor essential for heart development, is also expressed in cardiac fibroblasts. However, it remains elusive about the role of Gata4 in cardiac fibroblasts. To define the role of Gata4 in cardiac fibroblasts, we generated cardiac fibroblast-specific Gata4 knockout mice by cross-breeding Tcf21-MerCreMer mice with Gata4fl/fl mice. Using this mouse model, we could genetically ablate Gata4 in Tcf21 positive cardiac fibroblasts in an inducible manner upon tamoxifen administration. We found that cardiac fibroblast-specific deletion of Gata4 spontaneously induces senescence in cardiac fibroblasts in vivo and in vitro. We also found that Gata4 expression in both cardiomyocytes and non-myocytes significantly decreases in the aged heart. Interestingly, when αMHC-MerCreMer mice were bred with Gata4fl/fl mice to generate cardiomyocyte-specific Gata4 knockout mice, no senescent cells were detected in the hearts. Taken together, our results demonstrate that Gata4 deficiency in cardiac fibroblasts activates a program of cellular senescence, suggesting a novel molecular mechanism of cardiac fibroblast senescence.