bluuebunny/crossref_metadata_2025 huggingface dataset:
Human Polβ Natural Polymorphic Variants G118V and R149I Affects Substate Binding and Catalysis
Authors: Kladova Olga A. , Tyugashev Timofey E. , Mikushina Elena S. , Soloviev Nikita O. , Kuznetsov Nikita A. , Novopashina Daria S. , Kuznetsova Aleksandra A.
Published: March 2023

DNA polymerase β (Polβ) expression is essential for the cell’s response to DNA damage that occurs during natural cellular processes. Polβ is considered the main reparative DNA polymerase, whose role is to fill the DNA gaps arising in the base excision repair pathway. Mutations in Polβ can lead to cancer, neurodegenerative diseases, or premature aging. Many single-nucleotide polymorphisms have been identified in the POLB gene, but the consequences of these polymorphisms are not always clear. It is known that some polymorphic variants in the Polβ sequence reduce the efficiency of DNA repair, thereby raising the frequency of mutations in the genome. In the current work, we studied two polymorphic variants (G118V and R149I separately) of human Polβ that affect its DNA-binding region. It was found that each amino acid substitution alters Polβ’s affinity for gapped DNA. Each polymorphic variant also weakens its binding affinity for dATP. The G118V variant was found to greatly affect Polβ’s ability to fill gapped DNA and slowed the catalytic rate as compared to the wild-type enzyme. Thus, these polymorphic variants seem to decrease the ability of Polβ to maintain base excision repair efficiency.
An Uncommon Case of Moyamoya Syndrome Is Accompanied by an Arteriovenous Malformation with the Involvement of Dural Arteries
Authors: Nurimanov Chingiz , Mammadinova Iroda , Makhambetov Yerbol , Akshulakov Serik
Published: March 2023

(1) Background: This report describes the surgical management of a case of concurrent AVM with the involvement of dural arteries and moyamoya syndrome. Given the infrequency of this combination, there is currently no established management strategy available. (2) Case Description: A 49-year-old male patient with multiple symptoms including headaches, tinnitus, and visual impairment diagnosed with the coexistence of an arteriovenous malformation with the involvement of dural arteries and moyamoya syndrome was admitted to the national tertiary hospital. The patient underwent surgical management through embolization of the AVM from the afferents of the dural arteries, which has resulted in positive clinical outcomes. However, this approach may not be suitable for all cases, and a multidisciplinary team approach may be required to develop an individualized treatment strategy. (3) Conclusion: The contradictory nature of the treatment approaches in cases of combined AVM with the involvement of dural arteries and MMD highlights the complex nature of this condition and the need for further research to identify the most effective treatment strategies.
Time Dependent Changes in the Ovine Neurovascular Unit; A Potential Neuroprotective Role of Annexin A1 in Neonatal Hypoxic-Ischemic Encephalopathy
Authors: Park Hyun Young , van Bruggen Valéry L. E. , Peutz-Kootstra Carine J. , Ophelders Daan R. M. G. , Jellema Reint K. , Reutelingsperger Chris P. M. , Rutten Bart P. F. , Wolfs Tim G. A. M.
Published: March 2023

Perinatal brain injury following hypoxia-ischemia (HI) is characterized by high mortality rates and long-term disabilities. Previously, we demonstrated that depletion of Annexin A1, an essential mediator in BBB integrity, was associated with a temporal loss of blood-brain barrier (BBB) integrity after HI. Since the molecular and cellular mechanisms mediating the impact of HI are not fully scrutinized, we aimed to gain mechanistic insight into the dynamics of essential BBB structures following global HI in relation to ANXA1 expression. Global HI was induced in instrumented preterm ovine fetuses by transient umbilical cord occlusion (UCO) or sham occlusion (control). BBB structures were assessed at 1, 3, or 7 days post-UCO by immunohistochemical analyses of ANXA1, laminin, collagen type IV, and PDGFRβ for pericytes. Our study revealed that within 24 h after HI, cerebrovascular ANXA1 was depleted, which was followed by depletion of laminin and collagen type IV 3 days after HI. Seven days post-HI, increased pericyte coverage, laminin and collagen type IV expression were detected, indicating vascular remodeling. Our data demonstrate novel mechanistic insights into the loss of BBB integrity after HI, and effective strategies to restore BBB integrity should potentially be applied within 48 h after HI. ANXA1 has great therapeutic potential to target HI-driven brain injury.
IgG1 Is the Optimal Subtype for Treating Atherosclerosis by Inducing M2 Macrophage Differentiation, and Is Independent of the FcγRIIA Gene Polymorphism
Authors: Duan Rui , Liu Yan , Tang Dongmei , Lin Run , Huang Jinrong , Zhao Ming
Published: March 2023

In recent years, it has been established that atherosclerosis is an autoimmune disease. However, little is currently known about the role of FcγRIIA in atherosclerosis. Herein, we sought to investigate the relationship between FcγRIIA genotypes and the effectiveness of different IgG subclasses in treating atherosclerosis. We constructed and produced different subtypes of IgG and Fc-engineered antibodies. In vitro, we observed the effect of different subtypes of IgG and Fc-engineered antibodies on the differentiation of CD14+ monocytes from patients or healthy individuals. In vivo, Apoe−/− mice were fed a high-fat diet (HFD) for 20 weeks and administered injections of different CVI-IgG subclasses or Fc-engineered antibodies. Flow cytometry was used to assess the polarization of monocytes and macrophages. Although CVI-IgG4 reduced the release of MCP-1 compared to the other subtypes, IgG4 did not yield an anti-inflammatory effect by induction of human monocyte and macrophage differentiation in vitro. Furthermore, genetic polymorphisms of FcγRIIA were not associated with different CVI-IgG subclasses during the treatment of atherosclerosis. In vivo, CVI-IgG1 decreased Ly6Chigh monocyte differentiation and promoted M2 macrophage polarization. We also found that the secretion of IL-10 was upregulated in the CVI-IgG1-treated group, whereas V11 and GAALIE exerted no significant effect. These findings highlight that IgG1 is the optimal subtype for treating atherosclerosis, and CVI-IgG1 can induce monocyte/macrophage polarization. Overall, these results have important implications for the development of therapeutic antibodies.
Oxygen-Releasing Hyaluronic Acid-Based Dispersion with Controlled Oxygen Delivery for Enhanced Periodontal Tissue Engineering
Authors: Müller-Heupt Lena Katharina , Wiesmann-Imilowski Nadine , Schröder Sofia , Groß Jonathan , Ziskoven Pablo Cores , Bani Philipp , Kämmerer Peer Wolfgang , Schiegnitz Eik , Eckelt Anja , Eckelt John , Ritz Ulrike , Opatz Till , Al-Nawas Bilal , Synatschke Christopher V. , Deschner James
Published: March 2023

Periodontitis is a chronic biofilm-associated inflammatory disease of the tooth-supporting tissues that causes tooth loss. It is strongly associated with anaerobic bacterial colonization and represents a substantial global health burden. Due to a local hypoxic environment, tissue regeneration is impaired. Oxygen therapy has shown promising results as a potential treatment of periodontitis, but so far, local oxygen delivery remains a key technical challenge. An oxygen (O2)-releasing hyaluronic acid (HA)-based dispersion with a controlled oxygen delivery was developed. Cell viability of primary human fibroblasts, osteoblasts, and HUVECs was demonstrated, and biocompatibility was tested using a chorioallantoic membrane assay (CAM assay). Suppression of anaerobic growth of Porphyromonas gingivalis was shown using the broth microdilution assay. In vitro assays showed that the O2-releasing HA was not cytotoxic towards human primary fibroblasts, osteoblasts, and HUVECs. In vivo, angiogenesis was enhanced in a CAM assay, although not to a statistically significant degree. Growth of P. gingivalis was inhibited by CaO2 concentrations higher than 256 mg/L. Taken together, the results of this study demonstrate the biocompatibility and selective antimicrobial activity against P. gingivalis for the developed O2-releasing HA-based dispersion and the potential of O2-releasing biomaterials for periodontal tissue regeneration.
Incidence and Risk Factors for Long-Term Persistence of Diastolic Dysfunction after Aortic Valve Replacement for Aortic Stenosis Compared with Aortic Regurgitation
Authors: Iliuță Luminița , Andronesi Andreea Gabriella , Scafa-Udriște Alexandru , Rădulescu Bogdan , Moldovan Horațiu , Furtunescu Florentina Ligia , Panaitescu Eugenia
Published: March 2023

(1) Background: Severe left ventricular (LV) diastolic dysfunction with a restrictive diastolic pattern (LVDFP) is generally associated with a worse prognosis. Its evolution and reversibility in the short- and medium-term after aortic valve replacement (AVR) has been little-studied. We aimed to evaluate the evolution of LV remodeling and LV systolic and diastolic function after AVR in aortic stenosis (AS) patients compared to aortic regurgitation (AR). Moreover, we tried to identify the main predictive parameters for postoperative evolution (cardiovascular hospitalization or death and quality of life) and the independent predictors for the persistence of restrictive LVDFP after AVR. (2) Methods: A five-year prospective study on 397 patients undergoing AVR for AS (226 pts) or AR (171 pts), evaluated clinically and by echocardiography preoperatively and until 5 years postoperatively. (3) Results: 1. In patients with AS, early post AVR, LV dimensions decreased and diastolic filling and LV ejection fraction (LVEF) improved more rapidly compared to patients with AR. At 1 year postoperatively, persistent restrictive LVDFP was found especially in the AR group compared to the AS group (36.84% vs. 14.16%). 2. Cardiovascular event-free survival at the 5-year follow-up was lower in the AR group (64.91% vs. 87.17% in the AS group). The main independent predictors of short- and medium-term prognosis after AVR were: restrictive LVDFP, severe LV systolic dysfunction, severe pulmonary hypertension (PHT), advanced age, severe AR, and comorbidities. 3. The persistence of restrictive LVDFP after AVR was independently predicted by: preoperative AR, the E/Ea ratio > 12, the LA dimension index > 30 mm/m2, an LV endsystolic diameter (LVESD) > 55 mm, severe PHT, and associated second-degree MR (p < 0.05). (4) Conclusions: AS patients had an immediate postoperative evolution in terms of LV remodeling, and LV systolic and diastolic function were more favorable compared to those with AR. The restrictive LVDFP was reversible, especially after the AVR for AS. The main prognostic predictors were the presence of restrictive LVDFP, advanced age, preoperative AR, severe LV systolic dysfunction, and severe PHT.
Heart Diseases of Uncertain Etiology: A New Definition of Heart Failure for Epidemiological Studies
Authors: Puddu Paolo Emilio , Menotti Alessandro
Published: March 2023

It has been a long time since, in the spectrum of ischemic (IHD) or coronary (CHD) heart diseases, a differentiation was performed between the forms presenting with and those without pain [...]
Optimizing Adjuvant Therapy after Surgery for Colorectal Cancer Liver Metastases: A Systematic Review
Authors: Georgilis Emmanouil , Gavriatopoulou Maria , Tsilimigras Diamantis I. , Malandrakis Panagiotis , Theodosopoulos Theodosios , Ntanasis-Stathopoulos Ioannis
Published: March 2023

The liver is the most common site of colorectal cancer metastatic spread. Although metastasectomy is the gold standard for fit patients with resectable colorectal cancer liver metastases (CRLMs), their management after surgical treatment remains controversial. The objective of this systematic review was to collate the currently available data of the agents used in the adjuvant setting in order to define the most optimal therapeutic strategy. A systematic review of the literature was conducted by searching PubMed/Medline and Cochrane library databases. We included studies that evaluated the efficacy, the tolerability and the safety profile of various chemotherapeutic agents that are used as adjuvant treatment after surgical resection of CRLMs. The outcomes of interest were regression-free survival (RFS), disease-free survival (DFS), overall survival (OS) and severe toxicities. From 543 initial articles, 29 publications with 7028 patients were finally included. In general, the results of the eligible studies indicated that adjuvant therapy after resection of CRLMs led to improved RFS/DFS rates, but this benefit did not contribute to a statistically significant prolongation of OS. Moreover, the choice of the therapeutic strategy, namely systematic or regional chemotherapy or the combination of both, did not seem to have a differential impact on patient outcomes. However, these results should be interpreted with caution since the majority of the chosen studies are of low or moderate quality. In this context, further high-quality clinical trials conducted on patient sub-populations with modern therapies are required in order to reduce in-study and between-study heterogeneity and determine which patients are expected to derive the maximum benefit from adjuvant therapy after surgery for CRLMs.
The Association between CFTR Gene Mutation Heterozygosity and Asthma Development: A Systematic Review
Authors: Koumpagioti Despoina , Moriki Dafni , Boutopoulou Barbara , Matziou Vasiliki , Loukou Ioanna , Priftis Kostas N. , Douros Konstantinos
Published: March 2023

Asthma is caused by complex interactions between environmental and genetic factors. Various genes have been implicated as potential risk factors in the development of asthma; among them is cystic fibrosis transmembrane conductance regulator (CFTR) gene. The aim of this systematic review was to investigate the association of CFTR mutation heterozygosity with the development of asthma, by updating the existing data with recent studies’ findings. Therefore, a systematic review of the literature was conducted on Pubmed, ESBCO (Cinahl) and Scopus Databases up to December 2022. After the eligibility assessment, 17 studies were included in this review. Nine of them supported a lack of relationship between CFTR mutation heterozygosity and asthma susceptibility, and eight reported a positive association. Consequently, more extensive research is needed through high-quality studies to provide valid evidence and highlight the clinical benefits of identifying CFTR mutations in asthma patients, their impact on asthma severity, or treatment perspectives.
Pyridostigmine Bromide Pills and Pesticides Exposure as Risk Factors for Eye Disease in Gulf War Veterans
Authors: Truax Lauren E. , Huang Jaxon J. , Jensen Katherine , Locatelli Elyana V. T. , Cabrera Kimberly , Peterson Haley O. , Cohen Noah K. , Mangwani-Mordani Simran , Jensen Andrew , Goldhardt Raquel , Galor Anat
Published: March 2023

To examine associations between the pyridostigmine bromide (PB) pill and/or pesticide exposure during the 1990–1991 Gulf War (GW) and eye findings years after deployment. A cross-sectional study of South Florida veterans who were deployed on active duty during the GW Era (GWE). Information on GW exposures and ocular surface symptoms were collected via standardized questionnaires and an ocular surface examination was performed. Participants underwent spectral domain–ocular coherence tomography (SD-OCT) imaging that included retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), and macular maps. We examined for differences in eye findings between individuals exposed versus not exposed to PB pills or pesticides during service. A total of 40.7% (n = 44) of individuals reported exposure to PB pills and 41.7% (n = 45) to pesticides; additionally, 24 reported exposure to both in the GW arena. Demographics were comparable across groups. Individuals exposed to PB pills reported higher dry eye (DE) symptoms scores (the 5-Item Dry Eye Questionnaire, DEQ-5: 9.3 ± 5.3 vs. 7.3 ± 4.7, p = 0.04) and more intense ocular pain (average over the last week: 2.4 ± 2.6 vs. 1.5 ± 1.8, p = 0.03; Neuropathic Pain Symptom Inventory modified for the Eye (NPSI-E): 18.2 ± 20.0 vs. 10.8 ± 13.8, p = 0.03) compared to their non-exposed counterparts. DE signs were comparable between the groups. Individuals exposed to PB pills also had thicker OCT measurements, with the largest difference in the outer temporal segment of the macula (268.5 ± 22.2 μm vs. 260.6 ± 14.5 μm, p = 0.03) compared to non-exposed individuals. These differences remained significant when examined in multivariable models that included demographics and deployment history. Individuals exposed to pesticides had higher neuropathic ocular pain scores (NPSI-E: 17.1 ± 21.1 vs. 11.6 ± 12.9, p = 0.049), but this difference did not remain significant in a multivariable model. Individuals exposed to PB pills during the GWE reported more severe ocular surface symptoms and had thicker OCT measures years after deployment compared to their non-exposed counterparts.
Fusionless All-Pedicle Screws for Posterior Deformity Correction in AIS Immature Patients Permit the Restoration of Normal Vertebral Morphology and Removal of the Instrumentation Once Bone Maturity Is Reached
Authors: Burgos Jesús , Mariscal Gonzalo , Antón-Rodrigálvarez Luis Miguel , Sanpera Ignacio , Hevia Eduardo , García Vicente , Barrios Carlos
Published: March 2023

The aim of this study was to report the restoration of normal vertebral morphology and the absence of curve progression after the removal of instrumentation in AIS patients that underwent posterior correction of the deformity by a common all-screws construct without fusion. A series of 36 AIS immature patients (Risser 3 or less) were included in the study. Instrumentation was removed once the maturity stage was complete (Risser 5). The curve correction was assessed pre- and postoperatively, before instrumentation removal, directly post-removal, and more than two years after instrumentation was removed. Epiphyseal vertebral growth modulation was assessed by the coronal wedging ratio (WR) at the apical level of the main curve (MC). The mean preoperative coronal Cobb was corrected from 53.7° ± 7.5 to 5.5° ± 7.5° (89.7%) at the immediate postop. After implant removal (31.0 ± 5.8 months), the MC was 13.1°. T5–T12 kyphosis showed significant improvement from 19.0° before curve correction to 27.1° after implant removal (p < 0.05). Before surgery, the WR was 0.71 ± 0.06, and after removal, 0.98 ± 0.08 (p < 0.001). At the end of the follow-up, the mean sagittal range of motion (ROM) of the T12-S1 segment was 51.2 ± 21.0°. The SRS-22 scores improved from 3.31 ± 0.25 preoperatively to 3.68 ± 0.25 at the final assessment (p < 0.001). In conclusion, a fusionless posterior approach using common all-pedicle screws correctly constructed satisfactory scoliotic main curves and permitted the removal of instrumentation once bone maturity was reached. The final correction was highly satisfactory, and an acceptable ROM of the previously lower instrumented segments was observed.
S100B Protein but Not 3-Nitrotyrosine Positively Correlates with Plasma Ammonia in Patients with Inherited Hyperammonemias: A New Promising Diagnostic Tool?
Authors: Czarnecka Anna , Obara-Michlewska Marta , Wesół-Kucharska Dorota , Greczan Milena , Kaczor Magdalena , Książyk Janusz , Rokicki Dariusz , Zielińska Magdalena
Published: March 2023

Individuals with inherited hyperammonemias often present developmental and intellectual deficiencies which are likely to be exaggerated by hyperammonemia episodes in long-term outcomes. In order to find a new, systemic marker common to the course of congenital hyperammonemias, we decided to measure the plasma level of S100 calcium-binding protein B (S100B), which is associated with cerebral impairment. Further, we analyzed three mechanistically diverged but linked with oxidative–nitrosative stress biochemical parameters: 3-nitrotyrosine (3-NT), a measure of plasma proteins’ nitration; advanced oxidation protein products (AOPP), a measure of protein oxidation; and glutathione peroxidase (GPx) activity, a measure of anti-oxidative enzymatic capacity. The plasma biomarkers listed above were determined for the first time in congenital hyperammonemia. Also, the level of pro- and anti-inflammatory mediators (i.e., IL-12, IL-6, IL-8, TNF-α, IL-1β, and IL-10) and chemokines (IP-10, MCP-1, MIG, and RANTES) were quantified. S100B was positively correlated with plasma ammonia level, while noticeable levels of circulating 3-NT in some of the patients’ plasma did not correlate with ammonia concentration. Overall, the linear correlation between ammonia and S100B but not standard oxidative stress-related markers offers a unique perspective for the future identification and monitoring of neurological deficits risk-linked with hyperammonemia episodes in patients with inherited hyperammonemias. The S100B measure may support the development of therapeutic targets and clinical monitoring in these disorders.
Evolution of Antibiotic Resistance in Escherichia coli and Klebsiella pneumoniae Clinical Isolates in a Multi-Profile Hospital over 5 Years (2017–2021)
Authors: Mączyńska Beata , Frej-Mądrzak Magdalena , Sarowska Jolanta , Woronowicz Krystyna , Choroszy-Król Irena , Jama-Kmiecik Agnieszka
Published: March 2023

In recent years, we have witnessed a growing drug resistance among bacteria, which is associated with the use and availability of an increasing number of broad-spectrum antimicrobial agents, as well as with their irrational and excessive use. The present study aims to analyze changes in the drug resistance of Gram-negative Enterobacterales: Escherichia coli and Klebsiella pneumoniae, isolated from infections in a multi-profile hospital over five years (from 2017 to 2021). Among the practical outcomes of the evaluation of these data will be the possibility of determining changes in susceptibility to the antibiotics used in the hospital. In turn, this will help propose new therapeutic options, especially for empirical therapy that is necessary in severe infections. The analysis of the use of individual groups of antibiotics allowed for identification of the causes of the increasing resistance of Gram-negative bacilli. The highest number of infections whose etiological agent was K. pneumoniae ESBL(+) and E. coli ESBL(+) was observed in 2018. In the analyzed five-year period, the number of multi-resistant (MDR) K. pneumoniae strains increased successively, which seems to be related to the growing use, especially in the pandemic period, of broad-spectrum antibiotics, mainly penicillins with inhibitors, third-generation cephalosporins, and carbapenems.
Epidemiology of Immune-Mediated Glomerulopathies before and after SARS-CoV-2 Vaccination: A Tertiary Referral Hospital Experience
Authors: Zamora Jorge Iván , López-Martínez Marina , Patricio Liebana Marc , Leon Román Juan Carlos , Bermejo Sheila , Vergara Ander , Agraz Irene , Terrades Natalia Ramos , Azancot Maria Antonieta , Toapanta Nestor , Gabaldon Maria Alejandra , Soler Maria José
Published: March 2023

Background: Vaccination is a known trigger for the appearance of immune-mediated glomerulopathies (IMG). The appearance of IMG after SARS-CoV-2 vaccination with suspected causality has been described. Our aim is to analyze the incidence of IMG flares before and after SARS-CoV-2 vaccination in our center. Methods: All persons with native kidney biopsy (KB) from January 2019 to March 2022 in our center were included in the study. We compared the incidence of IMG before and after the start of vaccination. We also collected information about whether the patients had received a SARS-CoV-2 vaccine or have suffered from COVID in the six weeks before the IMG. We also evaluated the analytical characteristics of the outbreaks. Results: A total of 386 KB were studied. Of them, 86/218 (39.4%) were IMG performed pre- and 85/168 (50.6%) post-SV (029). The incidence of idiopathic nephrotic syndrome (INS), studied separately, was also significantly increased post-vaccination (n = 18 (10.7%)) compared to pre-vaccination (n = 11 (5%)) (p = 0.036). There were no differences in the incidence of vasculitis or IgA nephropathy. Up to 17 (20%) flares occurred 6 weeks before SARS-CoV-2 vaccination and only 2 (2.4%) within the first 6 weeks after SARS-CoV-2 infection. Within those 17 flares, the most common diagnosis was IgAN (n = 5 (29.4%)); a total of 14 (82.4%) received an mRNA vaccine and 9 (52.9%) took place after the 1st vaccine dose. There were 13 cases of minimal change disease (MCD) with debut/recurrence pre-SV and 20 MCD with debut/recurrence post-SV (p = 0.002). Conclusions: The incidence of IMG, INS and MCD flares in our center increased significantly after SARS-CoV-2 vaccination. Importantly, 20% of IMG flares took place within the first 6 weeks after receiving a vaccine dose, with the first dose being the riskiest one and IgAN the most frequent diagnosis.
Zinc Oxide Non-Eugenol Cement versus Resinous Cement on Single Implant Restoration: A Split-Mouth Study
Authors: Reda Rodolfo , Zanza Alessio , Bellanova Valentina , Patil Shankargouda , Bhandi Shilpa , Di Nardo Dario , Testarelli Luca
Published: March 2023

Cement-retained implant restorations still represents a widely used prosthetic solution today, considering the simple execution, the possibility of correcting the implant axis according to the dental axis and an extremely satisfactory aesthetic. The objective of the study is to evaluate whether resin-based cements are actually more aggressive towards the peri-implant tissue compared to zinc oxide cements. In the present study 18 patients (8 males and 10 females) were examined with a split-mouth design. The follow-up period for patients after delivery of the cement-retained single crown is a maximum of 48 months. A total of 36 implants were inserted and monitored during this period. Clinical and radiographic tests were carried out on all 36 implants, with constant re-evaluation, as well as the occurrence of some prosthetic or biological problems that brought the patient back to visit. The results for both cements were in line with the indications of the respective manufacturers. During the observational period, no implant failed, with a survival rate of 100% on these 36 implants. In conclusion, it is possible to establish that the number of decementations of the cement-retained crowns cemented with Temp Bond non-eugenol was higher, but not statistically significant. In contrast, the biological complications per implant and the MBL were significantly higher in the cement-retained crowns cemented with Implacem.
Long-Term Degradation Assessment of a Polyurethane-Based Surgical Adhesive—Assessment and Critical Consideration of Preclinical In Vitro and In Vivo Testing
Authors: Bremer Lisanne , Hagemeister Kerstin , Moss Michaela , Ernst Lisa , Tolba René H. , Jockenhoevel Stefan , Apel Christian
Published: March 2023

Tissue adhesives constitute a great possibility to improve conventional wound closure. In contrast to sutures, they enable nearly immediate hemostasis and can prevent fluid or air leaks. In the present study, a poly(ester)urethane-based adhesive was investigated which already proved to be suitable for different indications, such as reinforcing vascular anastomosis and sealing liver tissue. Using in vitro and in vivo setups, the degradation of the adhesives was monitored over a period of up to 2 years, to evaluate long-term biocompatibility and determine degradation kinetics. For the first time, the complete degradation of the adhesive was documented. In subcutaneous locations, tissue residues were found after 12 months and in intramuscular locations, tissue degradation was complete after about 6 months. A detailed histological evaluation of the local tissue reaction revealed good biocompatibility throughout the different degradation stages. After full degradation, complete remodeling to physiological tissue was observed at the implant locations. In addition, this study critically discusses common issues related to the assessment of biomaterial degradation kinetics in the context of medical device certification. This work highlighted the importance and encouraged the implementation of biologically relevant in vitro degradation models to replace animal studies or at least reduce the number of animals in preclinical testing prior to clinical studies. Moreover, the suitability of frequently used implantation studies based on ISO 10993-6 at standard locations was critically discussed, especially in light of the associated lack of reliable predictions for degradation kinetics at the clinically relevant site of implantation.
New Finding of Eggs and Leptocephalus for Muraenesox cinereus off Jeju Island, Korea and Its Relation to Environmental Variables
Authors: Ji Hwan-Sung , Yu Hyo-Jae , Lee Seung-Jong , Kang Sukyung , Kim Jin-Koo
Published: March 2023

The daggertooth pike conger, Muraenesox cinereus, is an important demersal fish species in East Asia but the catch amount has declined in recent years. Spawning areas of M. cinereus have not yet been determined; identifying these have serious implications for resource management. Ichthyoplankton surveys are an effective method of distinguishing fish spawning areas and periods. Fish eggs were sampled from the waters adjacent to South Korea in August 2020 and 2022 using a Multiple Opening/Closing Net and Environmental Sensing System or a bongo net. In 2021, M. cinereus eggs were not collected. Three unidentified eggs (2.0–2.2 mm in diameter) were collected from the southeastern sea of Jeju Island at a seawater depth of 20–30 m and temperature of 20–22 °C. Muraenesox cinereus preleptocephali were gathered at 10–20 m depths from Jeju Island’s southernmost and eastern sea areas. The eggs and preleptocephali were identified as M. cinereus by their mitochondrial DNA 16S rRNA sequences. This is a new finding of eggs and leptocephalus of Muraenesox cinereus off Jeju Island, South Korea, which increases our understanding of the recruitment process of M. cinereus to facilitate resource management and species conservation.
A State-Dependent Hypoplastic Bounding Surface Model for Gassy Sand
Authors: Wang Mingyuan , Sun Jizhu , Wang Yong
Published: March 2023

As a kind of partially saturated soil often containing dissolved gas with a high degree of saturation (S > 85%), gassy sand sediment widely exists in the marine environment all over the world. Due to the effect of gas dissolution and exsolution on the pore fluid compressibility, its stress–strain and pore pressure responses are quite different from those of common saturated and unsaturated soils when subjected to undrained loading. Since almost all the gas bubbles are occluded in the pore water of offshore gassy sand, the matric suction may be neglected, and an undrained constitutive model for gassy sand is developed based on the existing hypoplastic bounding surface model for saturated sand. Both Boyle’s and Henry’s laws are employed in the model to characterize the equilibrium behavior of the gas compressibility and solubility, and then the equivalent compressibility coefficient of the pore fluid is obtained. To avoid unrealistic volumetric expansion, the concepts of the critical state and state-dependent dilatancy stress ratio are incorporated to describe its ultimate shear strength and dilatancy characteristics, respectively. Finally, the triaxial undrained test results on gas-charged sand from Hangzhou Bay are analyzed at three initial saturation degrees of 85%, 90%, and 100%, and two effective confining pressures of 50 kPa and 200 kPa. Moreover, carbon dioxide (CO2) was selected in the test, and the samples were loose with a relative density of 30%. It is noted that a good agreement is achieved between the simulation results and the experimental data, including the influence of gas content and confining pressure on the shear dilatancy and the mean effective stress increase at the beginning of the effective stress path, among others.
Neural Network, Nonlinear-Fitting, Sliding Mode, Event-Triggered Control under Abnormal Input for Port Artificial Intelligence Transportation Robots
Authors: Zhu Yaping , Zhang Qiang , Liu Yang , Hu Yancai , Zhang Sihang
Published: March 2023

A new control algorithm was designed to solve the problems of actuator physical failure, remote network attack, and sudden change in trajectory curvature when a port’s artificial intelligence-based transportation robots track transportation in a freight yard. First of all, the nonlinear, redundant, saturated sliding surface was designed based on the redundant information of sliding mode control caused by the finite nature of control performance; the dynamic acceleration characteristic of super-twisted sliding mode reaching law was considered to optimize the control high frequency change caused by trajectory mutation; and an improved super-twist reaching law was designed. Then, a nonlinear factor was designed to construct a nonlinear, fault-tolerant filtering mechanism to compensate for the abnormal part of the unknown input that cannot be executed by adaptive neural network reconstruction. On this basis, the finite-time technology and parameter-event-triggered mechanism were combined to reduce the dependence on communication resources. As a result, the design underwent simulation verification to verify its effectiveness and superiority. In the comparative simulation, under a consistent probability of a network attack, the tracking accuracy of the algorithm proposed in this paper was 22.65%, 12.69% and 11.48% higher those that of the traditional algorithms.
Automated Atmospheric Correction of Nanosatellites Using Coincident Ocean Color Radiometer Data
Authors: McCarthy Sean , Crawford Summer , Wood Christopher , Lewis Mark D. , Jolliff Jason K. , Martinolich Paul , Ladner Sherwin , Lawson Adam , Montes Marcos
Published: March 2023

Here we present a machine-learning-based method for utilizing traditional ocean-viewing satellites to perform automated atmospheric correction of nanosatellite data. These sensor convolution techniques are required because nanosatellites do not usually possess the wavelength combinations required to atmospherically correct upwelling radiance data for oceanographic applications; however, nanosatellites do provide superior ground-viewing spatial resolution (~3 m). Coincident multispectral data from the Suomi National Polar-Orbiting Partnership Visible Infrared Imaging Radiometer Suite (Suomi NPP VIIRS; referred to herein as “VIIRS”) were used to remove atmospheric contamination at each of the nanosatellite’s visible wavelengths to yield an estimate of spectral water-leaving radiance [Lw(l)], which is the basis for surface ocean optical products. Machine learning (ML) algorithms (KNN, decision tree regressors) were applied to determine relationships between Lw and top-of-atmosphere (Lt)/Rayleigh (Lr) radiances within VIIRS training data, and then applied to test cases for (1) the Marine Optical Buoy (MOBY) in Hawaii and (2) the AErosol RObotic Network Ocean Color (AERONET-OC), Venice, Italy. For the test cases examined, ML-based methods appeared to improve statistical results when compared to alternative dark spectrum fitting (DSF) methods. The results suggest that ML-based sensor convolution techniques offer a viable path forward for the oceanographic application of nanosatellite data streams.
Numerical Analysis of Flow Characteristics in Impeller-Guide Vane Hydraulic Coupling Zone of an Axial-Flow Pump as Turbine Device
Authors: Yang Fan , Li Zhongbin , Lv Yuting , Li Jindong , Zhou Guangxin , Nasr Ahmed
Published: March 2023

An axial-flow pump as a turbine (PAT), as compared to the conventional Francis turbine, has the advantages of not being restricted by the terrain and having lower cost to reverse the pump as a turbine for power generation. When an axial-flow pump is reversed as a turbine, the internal flow pattern is more complicated than when in the pump mode, which can cause instability in the whole system and result in degradation of the hydraulic performance and structural vibration. The impeller and guide vane are the core of the axial-flow PAT unit. This research compares the experimental and numerical simulation results in order to verify the energy performance and pressure pulsation signal of the axial-flow PAT. The unsteady flow regime, fluid force, and pressure pulsation characteristics of the impeller-guide vane hydraulic coupling zone are analyzed in detail. The findings demonstrate that both the dominant frequency of the fluid force pulsation signal and the flow field pressure pulsation signal appear at 3 times of the rotation frequency. The blade passing frequency (BPF) of the impeller is the dominant frequency, and other frequency components are also dominated by the harmonic frequency of the BPF. The impeller and guide vane are primarily subject to radial fluid force. Under partial working conditions, the pressure pulsation intensity in the flow field greatly increases, and the pressure pulsation amplitude at the guide vane outlet and impeller outlet appears to be more sensitive to the flow rate change.
The Role of Folic Acid in SARS-CoV-2 Infection: An Intriguing Linkage under Investigation
Authors: Karakousis Nikolaos D. , Gourgoulianis Konstantinos I. , Kotsiou Ourania S.
Published: March 2023

Background: SARS-CoV-2 is a life-threatening RNA virus that may cause an acute respiratory syndrome associated with extremely high morbidity and mortality rates. Folic acid (FA), also known as folate, is an essential vitamin vital for human homeostasis, participating in many biochemical pathways, and its deficiency has been associated with viral infection vulnerability. In this review, we investigated the association between FA intake and SARS-CoV-2 infection, along with the existence of any potential impact of FA on the health outcome of patients suffering from this new viral infection. Methods: Studies included were patients’ and in silico and molecular docking studies. Results: Data from in silico studies and molecular docking support that FA inhibits SARS-CoV-2 entry into the host and viral replication, binding at essential residues. Accordingly, in patients’ studies, a protective role of FA supplementation against SARS-CoV-2 infection is indicated. However, contradictory data from observational studies indicate that FA supplementation, often linked to deficits during systemic inflammation due to SARS-CoV-2, increases the risk of post-infection mortality. Conclusions: Future randomized controlled trial studies, including the FA pharmacological group, are needed to better understand the role of FA as a potential protective or mortality risk indicator in COVID-19 patients.
Cochlear Implantation in Pediatrics: The Effect of Cochlear Coverage
Authors: Alothman Noura , Almuhawas Fida , Badghaish Reem , Alotaibi Al Hanouf , Alhabib Salman F. , Alzhrani Farid , Hagr Abdulrahman
Published: March 2023

The effect of insertion depth and position of cochlear implant (CI) electrode arrays on speech perception remains unclear. This study aimed to determine the relationship between cochlear coverage and speech performance in children with prelingual hearing loss with CI. Pure tone audiometry (PTA) and speech audiometry, including speech reception threshold (SRT) using spondee words and speech discrimination score (SDS) using phonetically balanced monosyllabic words, were tested. The Categories of Auditory Performance (CAP) and Speech Intelligibility Rating (SIR) scales were also used. Thirty-one ears were implanted with the FLEX 28 electrode array, and 54 with the FORM 24 were included in the current study. For the studied ear, the mean cochlear duct length was 30.82 ± 2.24 mm; the mean cochlear coverage was 82.78 ± 7.49%. Cochlear coverage was a significant negative predictor for the mean pure tone threshold across frequecnies of 0.5, 1, 2, and 4 kHz (PTA4) (p = 0.019). Cochlear coverage was a significant positive predictor of SDS (p = 0.009). In children with cochlear coverage ≥ 82.78%, SDS was significantly better than in those with coverage < 82.78% (p = 0.04). Cochlear coverage was not a significant predictor of the SRT, CAP, or SIR. In conclusion, the cochlear coverage of the CI electrode array has an impact on the users’ SDS. Further long-term studies with larger sample sizes should be conducted to address the most critical factors affecting CI recipients’ outcomes.
The Threat of COVID-19 on Food Security: A Modelling Perspective of Scenarios in the Informal Settlements in Windhoek
Authors: Nickanor Ndeyapo M. , Tawodzera Godfrey , Kazembe Lawrence N.
Published: March 2023

Due to the heterogeneity among households across locations, predicting the impacts of stay-at-home mitigation and lockdown strategies for COVID-19 control is crucial. In this study, we quantitatively assessed the effects of the Namibia government’s lockdown control measures on food insecurity in urban informal settlements with a focus on Windhoek, Namibia. We developed three types of conditional regression models to predict food insecurity prevalence (FIP) scenarios incorporating household frequency of food purchase (FFP) as the impacting factor, based on the Hungry Cities Food Matrix. Empirical data were derived from the 2017 African Food Security Urban Network (AFSUN) Windhoek study and applied univariate probit and bivariate partial observability models to postulate the relation between food insecurity and FFP within the context of stay-at-home disease mitigation strategy. The findings showed that FFP was positively correlated with the prevalence of food insecurity (r = 0.057, 95% CI: 0.0394, 0.085). Daily purchases portrayed a survivalist behaviour and were associated with increased food insecurity (coeff = 0.076, p = 0.05). Only those who were purchasing food twice monthly were significantly associated with reduced food insecurity (coeff = −0.201, p = 0.001). Those households in informal settlements were severely impacted by food insecurity (coeff = 0.909, p-value = 0.007). We conclude that public health compliance should precede with cash or food support to poor households in balance with the need for long-term placement of control measures to fully contain COVID-19 or related infectious diseases.
An Experimental Investigation of Multiple Sluicing in Mandarin Chinese
Authors: Bai Xue , Cortés Rodríguez Álvaro , Takahashi Daiko
Published: March 2023

This paper examines multiple sluicing constructions in Mandarin Chinese (henceforth, MC) experimentally. The acceptability status of such constructions in MC is controversial, and the judgments reported in the previous literature vary. Obtaining experimental evidence on the acceptability status is, therefore, important to advance the research on multiple sluicing in MC. Consequently, the present study conducts two sets of experiments to investigate factors affecting the acceptability of multiple sluicing sentences and the influence of the distribution of shi preceding wh-remnants on acceptability ratings. The results show that multiple sluicing in MC is generally a marked construction. Nevertheless, factors including prepositionhood and specificity have ameliorating effects on the acceptability of such constructions. Moreover, the influence of the distribution of shi on the acceptability ratings is related to the nature of wh-remnants; that is, its presence significantly improves the acceptability of cases of multiple sluicing when it precedes bare wh-arguments. We argue that the observed ameliorating effects on multiple sluicing can be explained by a cue-based retrieval approach to cross-linguistic elliptical constructions. Compared to bare wh-arguments, prepositional and discourse-linked wh-phrases provide cues to facilitate the retrieval of information from antecedent clauses.
Autonomic Nervous System Adaptation and Circadian Rhythm Disturbances of the Cardiovascular System in a Ground-Based Murine Model of Spaceflight
Authors: Hélissen Ophélie , Kermorgant Marc , Déjean Sébastien , Mercadie Aurélie , Le Gonidec Sophie , Zahreddine Rana , Calise Denis , Nasr Nathalie , Galès Céline , Arvanitis Dina N. , Pavy-Le Traon Anne
Published: March 2023

Whether in real or simulated microgravity, Humans or animals, the kinetics of cardiovascular adaptation and its regulation by the autonomic nervous system (ANS) remain controversial. In this study, we used hindlimb unloading (HU) in 10 conscious mice. Blood pressure (BP), heart rate (HR), temperature, and locomotor activity were continuously monitored with radio-telemetry, during 3 days of control, 5 days of HU, and 2 days of recovery. Six additional mice were used to assess core temperature. ANS activity was indirectly determined by analyzing both heart rate variability (HRV) and baroreflex sensitivity (BRS). Our study showed that HU induced an initial bradycardia, accompanied by an increase in vagal activity markers of HRV and BRS, together with a decrease in water intake, indicating the early adaptation to fluid redistribution. During HU, BRS was reduced; temperature and BP circadian rhythms were altered, showing a loss in day/night differences, a decrease in cycle amplitude, a drop in core body temperature, and an increase in day BP suggestive of a rise in sympathetic activity. Reloading induced resting tachycardia and a decrease in BP, vagal activity, and BRS. In addition to cardiovascular deconditioning, HU induces disruption in day/night rhythmicity of locomotor activity, temperature, and BP.
Mechanical Behaviour Evaluation of Full Iron Tailings Concrete Columns under Large Eccentric Short-Term Loading
Authors: Ma Xinxin , Sun Jianheng , Zhang Fengshuang , Yuan Jing , Yang Mingjing , Meng Zhiliang , Bai Yongbing , Liu Yunpeng
Published: March 2023

In this study, full iron tailings concrete (FITC) was created using iron tailings from a tailings pond in Qian’an, China. Iron tailings account for 86.8% of the total mass of solid raw materials in the FITC. To enable large-scale use of FITC, a comprehensive investigation of the structural behaviour of full-iron tailing-reinforced concrete (FITRC) specimens is warranted. Therefore, eight rectangular reinforced concrete (RC) columns with conventional reinforced concrete (CRC) as a control were tested to investigate the effects of section dimensions, initial eccentricities, and concrete strengths, on the structural behaviour of FITRC columns under large eccentric short-term loading. The experimental and analytical results indicated that the sectional strain of the FITRC columns satisfied the plane-section assumption under short-term loading, and the lateral deflection curve agreed well with the half-sinusoidal curve. In addition, the FITRC columns exhibited a slightly lower cracking load and lower ultimate load capacity than the CRC columns, and the crack widths were larger than those of the CRC columns. The reduction in the load capacity observed in the FITRC was within the permissible range stated in the design code, thereby satisfying the code requirements. The deformation coefficients of the FITRC and CRC columns were identical, and the cracking and ultimate loads calculated according to the current code and theories were in good agreement with the measured results.