bluuebunny/crossref_metadata_2025 huggingface dataset:
Biomarkers to Predict Lethal Radiation Injury to the Rat Lung
Authors: Medhora Meetha , Gao Feng , Gasperetti Tracy , Narayanan Jayashree , Himburg Heather , Jacobs Elizabeth R. , Clough Anne V. , Fish Brian L. , Szabo Aniko
Published: March 2023

Currently, there are no biomarkers to predict lethal lung injury by radiation. Since it is not ethical to irradiate humans, animal models must be used to identify biomarkers. Injury to the female WAG/RijCmcr rat has been well-characterized after exposure to eight doses of whole thorax irradiation: 0-, 5-, 10-, 11-, 12-, 13-, 14- and 15-Gy. End points such as SPECT imaging of the lung using molecular probes, measurement of circulating blood cells and specific miRNA have been shown to change after radiation. Our goal was to use these changes to predict lethal lung injury in the rat model, 2 weeks post-irradiation, before any symptoms manifest and after which a countermeasure can be given to enhance survival. SPECT imaging with 99mTc-MAA identified a decrease in perfusion in the lung after irradiation. A decrease in circulating white blood cells and an increase in five specific miRNAs in whole blood were also tested. Univariate analyses were then conducted on the combined dataset. The results indicated that a combination of percent change in lymphocytes and monocytes, as well as pulmonary perfusion volume could predict survival from radiation to the lungs with 88.5% accuracy (95% confidence intervals of 77.8, 95.3) with a p-value of < 0.0001 versus no information rate. This study is one of the first to report a set of minimally invasive endpoints to predict lethal radiation injury in female rats. Lung-specific injury can be visualized by 99mTc-MAA as early as 2 weeks after radiation.
Irradiation-Induced Dysbiosis: The Compounding Effect of High-Fat Diet on Metabolic and Immune Functions in Mice
Authors: Clifford Briana K. , Amorim Nadia M. L. , Kaakoush Nadeem O. , Boysen Lykke , Tedla Nicodemus , Goldstein David , Hardeman Edna C. , Simar David
Published: March 2023

The negative impact of irradiation or diet on the metabolic and immune profiles of cancer survivors have been previously demonstrated. The gut microbiota plays a critical role in regulating these functions and is highly sensitive to cancer therapies. The aim of this study was to investigate the effect of irradiation and diet on the gut microbiota and metabolic or immune functions. We exposed C57Bl/6J mice to a single dose of 6 Gy radiation and after 5 weeks, fed them a chow or high-fat diet (HFD) for 12 weeks. We characterised their faecal microbiota, metabolic (whole body and adipose tissue) functions, and systemic (multiplex cytokine, chemokine assay, and immune cell profiling) and adipose tissue inflammatory profiles (immune cell profiling). At the end of the study, we observed a compounding effect of irradiation and diet on the metabolic and immune profiles of adipose tissue, with exposed mice fed a HFD displaying a greater inflammatory signature and impaired metabolism. Mice fed a HFD also showed altered microbiota, irrespective of irradiation status. An altered diet may exacerbate the detrimental effects of irradiation on both the metabolic and inflammatory profiles. This could have implications for the diagnosis and prevention of metabolic complications in cancer survivors exposed to radiation.
Changes in Memory, Sedation, and Receptor Kinetics Imparted by the β2-N265M and β3-N265M GABAA Receptor Point Mutations
Authors: Abdulzahir Alifayaz , Klein Steven , Lor Chong , Perkins Mark G. , Frelka Alyssa , Pearce Robert A.
Published: March 2023

Point mutations in the β2 (N265S) and β3 (N265M) subunits of γ-amino butyric acid type A receptors (GABAARs) that render them insensitive to the general anesthetics etomidate and propofol have been used to link modulation of β2-GABAARs to sedation and β3-GABAARs to surgical immobility. These mutations also alter GABA sensitivity, and mice carrying the β3-N265M mutation have been reported to have impaired baseline memory. Here, we tested the effects of the β2-N265M and β3-N265M mutations on memory, movement, hotplate sensitivity, anxiety, etomidate-induced sedation, and intrinsic kinetics. We found that both β2-N265M and β3-N265M mice exhibited baseline deficits in the Context Preexposure Facilitation Effect learning paradigm. Exploratory activity was slightly greater in β2-N265M mice, but there were no changes in either genotype in anxiety or hotplate sensitivity. β2-N265M mice were highly resistant to etomidate-induced sedation, and heterozygous mice were partially resistant. In rapid solution exchange experiments, both mutations accelerated deactivation two- to three-fold compared to wild type receptors and prevented modulation by etomidate. This degree of change in the receptor deactivation rate is comparable to that produced by an amnestic dose of etomidate but in the opposite direction, indicating that intrinsic characteristics of GABAARs are optimally tuned under baseline conditions to support mnemonic function.
Generation of Periventricular Reactive Astrocytes Overexpressing Aquaporin 4 Is Stimulated by Mesenchymal Stem Cell Therapy
Authors: García-Bonilla María , Ojeda-Pérez Betsaida , Shumilov Kirill , Rodríguez-Pérez Luis-Manuel , Domínguez-Pinos Dolores , Vitorica Javier , Jiménez Sebastián , Ramírez-Lorca Reposo , Echevarría Miriam , Cárdenas-García Casimiro , Iglesias Teresa , Gutiérrez Antonia , McAllister James P. , Limbrick David D. , Páez-González Patricia , Jiménez Antonio J.
Published: March 2023

Aquaporin-4 (AQP4) plays a crucial role in brain water circulation and is considered a therapeutic target in hydrocephalus. Congenital hydrocephalus is associated with a reaction of astrocytes in the periventricular white matter both in experimental models and human cases. A previous report showed that bone marrow-derived mesenchymal stem cells (BM-MSCs) transplanted into the lateral ventricles of hyh mice exhibiting severe congenital hydrocephalus are attracted by the periventricular astrocyte reaction, and the cerebral tissue displays recovery. The present investigation aimed to test the effect of BM-MSC treatment on astrocyte reaction formation. BM-MSCs were injected into the lateral ventricles of four-day-old hyh mice, and the periventricular reaction was detected two weeks later. A protein expression analysis of the cerebral tissue differentiated the BM-MSC-treated mice from the controls and revealed effects on neural development. In in vivo and in vitro experiments, BM-MSCs stimulated the generation of periventricular reactive astrocytes overexpressing AQP4 and its regulatory protein kinase D-interacting substrate of 220 kDa (Kidins220). In the cerebral tissue, mRNA overexpression of nerve growth factor (NGF), vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1 (HIF1α), and transforming growth factor beta 1 (TGFβ1) could be related to the regulation of the astrocyte reaction and AQP4 expression. In conclusion, BM-MSC treatment in hydrocephalus can stimulate a key developmental process such as the periventricular astrocyte reaction, where AQP4 overexpression could be implicated in tissue recovery.
The APSANTICO Study: A Prospective Observational Study to Evaluate Antiphospholipid Antibody Profiles in Patients with Thromboembolic Antiphospholipid Syndrome (APS) after COVID-19 Infection and/or Vaccination
Authors: Ott Olivia , Herrmann Eva , Schulz Annabel , Lindhoff-Last Edelgard
Published: March 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new virus discovered in December 2019 that causes coronavirus disease 19 (COVID-19) and various vaccinations have been developed. The extent to which COVID-19 infections and/or COVID-19 vaccinations alter antiphospholipid antibodies (aPL) in patients with thromboembolic antiphospholipid syndrome (APS) remains unclear. Eighty-two patients with confirmed thromboembolic APS were included in this prospective non-interventional trial. Blood parameters including lupus anticoagulants, anticardiolipin IgG- and IgM-antibodies, and anti-ß2-glycoprotein I IgG- and IgM-antibodies were assessed prior to and after COVID-19 vaccination and/or COVID-19 infection. No increases in aPL in the total study population were detected. In fact, low but significant decreases were observed for anticardiolipin IgG- and anti-β2-glycoprotein I IgG-antibodies, while anticardiolipin IgM- and anti-b2-glycoprotein I IgM-antibodies slightly increased only in patients with COVID-19 infection and vaccination. Although the investigated patient group is known to have a high risk of recurrent thrombosis, only one arterial thrombotic event was diagnosed (1.2%, 1/82). This low recurrence rate was probably due to the high vaccination rates prior to infections and a high rate of effective anticoagulation. Our data show that COVID-19 infections and/or vaccinations do not deteriorate the clinical course of anticoagulated thromboembolic APS patients.
Strain-Specific Interactions between the Viral Capsid Proteins VP4, VP7 and VP6 Influence Rescue of Rotavirus Reassortants by Reverse Genetics
Authors: Valusenko-Mehrkens Roman , Gadicherla Ashish K. , Johne Reimar , Falkenhagen Alexander
Published: March 2023

Rotavirus A (RVA) genome segments can reassort upon co-infection of target cells with two different RVA strains. However, not all reassortants are viable, which limits the ability to generate customized viruses for basic and applied research. To gain insight into the factors that restrict reassortment, we utilized reverse genetics and tested the generation of simian RVA strain SA11 reassortants carrying the human RVA strain Wa capsid proteins VP4, VP7, and VP6 in all possible combinations. VP7-Wa, VP6-Wa, and VP7/VP6-Wa reassortants were effectively rescued, but the VP4-Wa, VP4/VP7-Wa, and VP4/VP6-Wa reassortants were not viable, suggesting a limiting effect of VP4-Wa. However, a VP4/VP7/VP6-Wa triple-reassortant was successfully generated, indicating that the presence of homologous VP7 and VP6 enabled the incorporation of VP4-Wa into the SA11 backbone. The replication kinetics of the triple-reassortant and its parent strain Wa were comparable, while the replication of all other rescued reassortants was similar to SA11. Analysis of the predicted structural protein interfaces identified amino acid residues, which might influence protein interactions. Restoring the natural VP4/VP7/VP6 interactions may therefore improve the rescue of RVA reassortants by reverse genetics, which could be useful for the development of next generation RVA vaccines.
The Role of IL-13 and IL-4 in Adipose Tissue Fibrosis
Authors: Arndt Lilli , Lindhorst Andreas , Neugebauer Julia , Hoffmann Anne , Hobusch Constance , Alexaki Vasileia-Ismini , Ghosh Adhideb , Blüher Matthias , Wolfrum Christian , Glaß Markus , Gericke Martin
Published: March 2023

White adipose tissue (WAT) fibrosis, characterized by an excess of extracellular (ECM) matrix components, is strongly associated with WAT inflammation and dysfunction due to obesity. Interleukin (IL)-13 and IL-4 were recently identified as critical mediators in the pathogenesis of fibrotic diseases. However, their role in WAT fibrosis is still ill-defined. We therefore established an ex vivo WAT organotypic culture system and demonstrated an upregulation of fibrosis-related genes and an increase of α-smooth muscle actin (αSMA) and fibronectin abundance upon dose-dependent stimulation with IL-13/IL-4. These fibrotic effects were lost in WAT lacking il4ra, which encodes for the underlying receptor controlling this process. Adipose tissue macrophages were found to play a key role in mediating IL-13/IL-4 effects in WAT fibrosis as their depletion through clodronate dramatically decreased the fibrotic phenotype. IL-4-induced WAT fibrosis was partly confirmed in mice injected intraperitoneally with IL-4. Furthermore, gene correlation analyses of human WAT samples revealed a strong positive correlation of fibrosis markers with IL-13/IL-4 receptors, whereas IL13 and IL4 correlations failed to confirm this association. In conclusion, IL-13 and IL-4 can induce WAT fibrosis ex vivo and partly in vivo, but their role in human WAT remains to be further elucidated.
Comparative Gut Microbiome Differences between High and Low Aortic Arch Calcification Score in Patients with Chronic Diseases
Authors: Liu Yi-Hsueh , Peng Po , Hung Wei-Chun , Wu Ping-Hsun , Kao Cheng-Yuan , Wu Pei-Yu , Huang Jiun-Chi , Hung Chih-Hsing , Su Ho-Ming , Chen Szu-Chia , Kuo Chao-Hung
Published: March 2023

Gut dysbiosis can induce chronic inflammation and contribute to atherosclerosis and vascular calcification. The aortic arch calcification (AoAC) score is a simple, noninvasive, and semiquantitative assessment tool to evaluate vascular calcification on chest radiographs. Few studies have discussed the relationship between gut microbiota and AoAC. Therefore, this study aimed to compare the microbiota composition between patients with chronic diseases and high or low AoAC scores. A total of 186 patients (118 males and 68 females) with chronic diseases, including diabetes mellitus (80.6%), hypertension (75.3%), and chronic kidney disease (48.9%), were enrolled. Gut microbiota in fecal samples were analyzed by sequencing of the 16S rRNA gene, and differences in microbial function were examined. The patients were divided into three groups according to AoAC score, including 103 patients in the low AoAC group (AoAC ≤ 3), 40 patients in the medium AoAC group (3 < AoAC ≤ 6), and 43 patients in the high AoAC group (AoAC > 6). Compared to the low AoAC group, the high AoAC group had a significantly lower microbial species diversity (Chao1 index and Shannon index) and increased microbial dysbiosis index. Beta diversity showed that the microbial community composition was significantly different among the three groups (p = 0.041, weighted UniFrac PCoA). A distinct microbial community structure was found in the patients with a low AoAC, with an increased abundance at the genus level of Agathobacter, Eubacterium coprostanoligenes group, Ruminococcaceae UCG-002, Barnesiella, Butyricimonas, Oscillibacter, Ruminococcaceae DTU089, and Oxalobacter. In addition, there was an increased relative abundance of class Bacilli in the high AoAC group. Our findings support the association between gut dysbiosis and the severity of AoAC in patients with chronic diseases.
A Comparative Study of the Inhibitory Action of Berberine Derivatives on the Recombinant Protein FtsZ of E. coli
Authors: Di Somma Angela , Canè Carolina , Rotondo Natalie Paola , Cavalluzzi Maria Maddalena , Lentini Giovanni , Duilio Angela
Published: March 2023

Medicinal plants belonging to the genus Berberis may be considered an interesting source of drugs to counteract the problem of antimicrobial multiresistance. The important properties associated with this genus are mainly due to the presence of berberine, an alkaloid with a benzyltetrahydroisoquinoline structure. Berberine is active against both Gram-negative and Gram-positive bacteria, influencing DNA duplication, RNA transcription, protein synthesis, and the integrity of the cell surface structure. Countless studies have shown the enhancement of these beneficial effects following the synthesis of different berberine analogues. Recently, a possible interaction between berberine derivatives and the FtsZ protein was predicted through molecular docking simulations. FtsZ is a highly conserved protein essential for the first step of cell division in bacteria. The importance of FtsZ for the growth of numerous bacterial species and its high conservation make it a perfect candidate for the development of broad-spectrum inhibitors. In this work, we investigate the inhibition mechanisms of the recombinant FtsZ of Escherichia coli by different N-arylmethyl benzodioxolethylamines as berberine simplified analogues appropriately designed to evaluate the effect of structural changes on the interaction with the enzyme. All the compounds determine the inhibition of FtsZ GTPase activity by different mechanisms. The tertiary amine 1c proved to be the best competitive inhibitor, as it causes a remarkable increase in FtsZ Km (at 40 μM) and a drastic reduction in its assembly capabilities. Moreover, a fluorescence spectroscopic analysis carried out on 1c demonstrated its strong interaction with FtsZ (Kd = 26.6 nM). The in vitro results were in agreement with docking simulation studies.
Cell Intrinsic IL-38 Affects B Cell Differentiation and Antibody Production
Authors: Huard Arnaud , Wilmes Christian , Kiprina Anastasiia , Netzer Christoph , Palmer Gaby , Brüne Bernhard , Weigert Andreas
Published: March 2023

IL-38 is an IL-1 family receptor antagonist with an emerging role in chronic inflammatory diseases. IL-38 expression has been mainly observed not only in epithelia, but also in cells of the immune system, including macrophages and B cells. Given the association of both IL-38 and B cells with chronic inflammation, we explored if IL-38 affects B cell biology. IL-38-deficient mice showed higher amounts of plasma cells (PC) in lymphoid organs but, conversely, lower levels of plasmatic antibody titers. Exploring underlying mechanisms in human B cells revealed that exogenously added IL-38 did not significantly affect early B cell activation or differentiation into plasma cells, even though IL-38 suppressed upregulation of CD38. Instead, IL-38 mRNA expression was transiently upregulated during the differentiation of human B cells to plasma cells in vitro, and knocking down IL-38 during early B cell differentiation increased plasma cell generation, while reducing antibody production, thus reproducing the murine phenotype. Although this endogenous role of IL-38 in B cell differentiation and antibody production did not align with an immunosuppressive function, autoantibody production induced in mice by repeated IL-18 injections was enhanced in an IL-38-deficient background. Taken together, our data suggest that cell-intrinsic IL-38 promotes antibody production at baseline but suppresses the production of autoantibodies in an inflammatory context, which may partially explain its protective role during chronic inflammation.
Peritoneal Mesothelioma in a High Volume Peritoneal Surface Malignancies Unit
Authors: Pereira Fernando , Pereira Mónica , Manzanedo Israel , Serrano Ángel , Pérez-Viejo Estibalitz
Published: March 2023

Diffuse malignant peritoneal mesothelioma (PM) is a rare neoplasm, traditionally associated with a poor prognosis. There are other varieties of PM that are even less frequent and of uncertain malignancy. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has achieved prolonged survival in selected patients. The aim of this study is to analyze the patients with PM assessed in our center. Clinicopathological characteristics, diagnostic procedures and survival results from patients with PM appraised at our unit, according to the applied treatment, were analyzed. Seventeen patients were assessed between 2007 and 2019. Three cases had multicystic PM that were treated with complete CRS + HIPEC; all patients are alive and free of disease after a long follow-up. Three other cases had biphasic PM; a curative treatment could be performed in none of them, and their survival was minimal (<6 moths). Lastly, 11 cases with epithelioid PM were treated. Two cases were considered unresectable at laparoscopy (PCI 39); one of them had a long survival (67 months) with three iterative laparoscopic palliatives HIPECs for refractory ascites. The other nine cases were treated with curative CRS + HIPEC, with a median PCI of 14 (range 4–25), and a median overall survival (OS) of 58 months, with a 5-year OS of 47.4%. In conclusion, CRS + HIPEC, when possible, appears to be the optimal treatment for patients with PM. Knowledge of this therapeutic option is crucial, both to offer it to patients and to avoid delays in their referral to appropriate centers for treatment.
Cryopreservation of Fetal Porcine Kidneys for Xenogeneic Regenerative Medicine
Authors: Matsui Kenji , Kinoshita Yoshitaka , Inage Yuka , Matsumoto Naoto , Morimoto Keita , Saito Yatsumu , Takamura Tsuyoshi , Matsunari Hitomi , Yamanaka Shuichiro , Nagashima Hiroshi , Kobayashi Eiji , Yokoo Takashi
Published: March 2023

Kidney xenotransplantation has been attracting attention as a treatment option for end-stage renal disease. Fetal porcine kidneys are particularly promising grafts because they can reduce rejection through vascularization from host vessels. We are proposing xenogeneic regenerative medicine using fetal porcine kidneys injected with human nephron progenitor cells. For clinical application, it is desirable to establish reliable methods for the preservation and quality assessment of grafts. We evaluated the differentiation potency of vitrified porcine fetal kidneys compared with nonfrozen kidneys, using an in vivo differentiation model. Fetal porcine kidneys connected to the bladder were frozen via vitrification and stored in liquid nitrogen. Several days later, they were thawed and transplanted under the retroperitoneum of immunocompromised mice. After 14 days, the frozen kidneys grew and differentiated into mature nephrons, and the findings were comparable to those of nonfrozen kidneys. In conclusion, we demonstrated that the differentiation potency of vitrified fetal porcine kidneys could be evaluated using this model, thereby providing a practical protocol to assess the quality of individual lots.
Role of Vitrectomy in Nontractional Refractory Diabetic Macular Edema
Authors: Ranno Stefano , Vujosevic Stela , Mambretti Manuela , Metrangolo Cristian , Alkabes Micol , Rabbiolo Giovanni , Govetto Andrea , Carini Elisa , Nucci Paolo , Radice Paolo
Published: March 2023

Background: Currently, the gold standard of diabetic macular edema (DME) treatment is anti-vascular endothelial growth factor (VEGF) injections, although a percentage of patients do not respond optimally. Vitrectomy with or without internal limiting membrane (ILM) peeling is a well-established treatment for DME cases with a tractional component while its role for nontractional cases is unclear. The aim of this study is to evaluate the role of vitrectomy with or without ILM peeling in nontractional refractory DME. Methods: We performed a retrospective review of twenty-eight eyes with nontractional refractory DME treated with vitrectomy at San Giuseppe Hospital, Milan, between 2016 and 2018. All surgeries were performed by a single experienced vitreoretinal surgeon. In 43.4% of cases, the ILM was peeled. Best corrected visual acuity and optical coherence tomography (OCT) scans were assessed preoperatively and at 6, 12, and 24 months post-vitrectomy. Results: The mean central macular thickness improved from 413.1 ± 84.4 to 291.3 ± 57.6 μm at two years (p < 0.0001). The mean logarithm of the minimum angle of resolution logMAR best-corrected visual acuity (BCVA) improved after two years, from 0.6 ± 0.2 to 0.2 ± 0.1 (p < 0.0001). We found no difference between ILM peeling vs. no ILM peeling group in terms of anatomical (p = 0.8) and visual outcome (p = 0.3). Eyes with DME and subfoveal serous retinal detachment (SRD) at baseline had better visual outcomes at the final visit (p = 0.001). Conclusions: We demonstrated anatomical and visual improvement of patients who underwent vitrectomy for nontractional refractory DME with and without ILM peeling. Improvement was greater in patients presenting subretinal fluid preoperatively.
Evaluation of Infective Endocarditis in Children: A 19-Year Retrospective Study in Taiwan
Authors: Chien Shao-Ju , Tseng Yi-Ju , Huang Ying-Hua , Liu Hsi-Yun , Wu Yi-Hua , Chang Ling-Sai , Yang Yao-Hsu , Lin Ying-Jui
Published: March 2023

Background: Infective endocarditis (IE) is an important cause of morbidity and mortality in pediatric patients with heart disease. Little literature has explored differences in the presentation of endocarditis in children with and without heart disease. This study aimed to compare the clinical outcomes and determine the risk of in-hospital death in the study population. Methods: Data were retrospectively collected from 2001 to 2019 from the Chang Gung Research Database (CGRD), which is the largest collection of multi-institutional electronic medical records in Taiwan. Children aged 0–20 years with IE were enrolled. We extracted and analyzed the demographic and clinical features, complications, microbiological information, and outcomes of each patient. Results: Of the 208 patients with IE, 114 had heart disease and 94 did not. Compared to those without heart disease, more streptococcal infections (19.3% vs. 2.1%, p < 0.001) and cardiac complications (29.8% vs. 6.4%, p < 0.001) were observed in patients with heart disease. Although patients with heart disease underwent valve surgery more frequently (43.9% vs. 8.5%, p < 0.001) and had longer hospital stays (28.5 vs. 12.5, p = 0.021), their mortality was lower than that of those without heart disease (3.5% vs. 10.6%, p = 0.041). Thrombocytopenia was independent risk factor for in-hospital mortality in pediatric patients with IE (OR = 6.56, 95% CI: 1.43–40.37). Conclusion: Among pediatric patients diagnosed with IE, microbiological and clinical features differed between those with and without heart disease. Platelet counts can be used as a risk factor for in-hospital mortality in pediatric patients with IE.
Numerical Analysis of Mechanical Behaviors of Composite Tensile Armored Flexible Risers in Deep-Sea Oil and Gas
Authors: Liu Hu , Li Meng , Shen Yijun
Published: March 2023

As oil and natural gas production continue to go deeper into the ocean, the flexible riser, as a connection to the surface of the marine oil and gas channel, will confront greater problems in its practical application. Composite materials are being considered to replace steel in the unbonded flexible pipe in order to successfully meet the lightweight and high-strength criteria of ultra-deep-water oil and gas production. The carbon-fiber-reinforced material substitutes the steel of the tensile armor layer with a greater strength-to-weight ratio. However, its performance in deep-water environments is less researched. To investigate the mechanical response of a carbon fiber composite flexible riser in the deep sea, this study establishes the ABAQUS quasi-static analysis model to predict the performance of the pipe. Considering the special constitutive relations of composite materials, the tensile stiffness of steel pipe and carbon fiber-reinforced composite flexible pipe are predicted. The results show that the replacement of steel strips with carbon fiber can provide 85.06% tensile stiffness while reducing the weight by 77.7%. Moreover, carbon-fiber-reinforced strips have a lower radial modulus, which may not be sufficient to cause buckling under axial compression, so the instability of the carbon fiber composite armor layer under axial compression is further studied in this paper; furthermore, the characteristics of axial stiffness are analyzed, and the effects of the friction coefficient and hydrostatic pressure are discussed.
Carbon Fiber Composites for Large-Scale Wind Turbine Blades: Applicability Study and Comprehensive Evaluation in China
Authors: Teng Hanwei , Li Shujian , Cao Zheng , Li Shuang , Li Changping , Ko Tae Jo
Published: March 2023

Wind energy is a type of clean energy that can address global energy shortages and environmental issues. Wind turbine blades are a critical component in capturing wind energy. Carbon fiber composites have been widely recognized for their excellent overall performance in large-scale wind turbine blades. However, in China, the wide application of carbon fiber composites in wind turbine blades still faces many problems and challenges. This paper examines the current state of carbon fiber composites for wind turbine blades and the geographical distribution characteristics of wind resources in China. The economic revenues from increasing the length of wind turbine blades in four typical wind farms, including offshore wind farms, are compared. Using a mathematical model, the energy efficiency of carbon fiber composites in the application of large wind turbine blades is evaluated from the aspects of cost, embedded energy, and carbon footprint. Further, the current relationship between supply and demand for the industrial structure of carbon fiber in China is revealed. The manufacturing technologies for carbon fiber composite wind turbine blades are analyzed, and corresponding countermeasures are proposed. Finally, the incentive policy for applying carbon fiber composites to wind turbine blades is explained, and the development prospects are explored. In this paper, the economics and energy efficiency of the application of carbon fiber composite materials in large wind turbine blades are analyzed and comprehensively evaluated by using mathematical models, which will provide a valuable reference for China’s wind turbine blade industry.
NeuTHOR Station—A Novel Integrated Platform for Monitoring BNCT Clinical Treatment, Animal and Cell Irradiation Study at THOR
Authors: Huang Yu-Shiang , Peir Jinn-Jer , Wu Chuan-Jen , Wang Mei-Ya , Chen Yi-Wei , Lee Jia-Cheng , Chou Fong-In
Published: March 2023

(1) Background: A well-established Boron Neutron Capture Therapy (BNCT) facility includes many essential systems, which are the epithermal neutron beam system, on-line monitoring system (OMS), QA/QC (quality assurance or quality control) system, boron concentration (BC) measurement system, and treatment planning system (TPS). Accurate data transmission, monitoring, and deposition among these systems are of vital importance before, during, and after clinical, animal, and cell BNCT irradiation. This work developed a novel integrated platform NeuTHOR Station (NeuTHORS) for BNCT at Tsing Hua Open-pool Reactor (THOR). Apart from the data of the OMS and QA/QC system, the data of BC and TPS can be loaded on NeuTHORS before BNCT clinical, animal, and cell irradiation. (2) Methods: A multi-paradigm computer programming language c# (c sharp) was used to develop the integrated platform NeuTHORS. The design of NeuTHORS is based on the standard procedures of BNCT treatment or experiment at THOR. Moreover, parallel testing with OMS-BNCT (the former OMS) and QA/QC of THOR was also performed for more than 70 times to verify the validation of NeuTHORS. (3) Results: According to the comparisons of the output, NeuTHORS and OMS-BNCT and QA/QC of THOR show very good consistency. NeuTHORS is now installed on an industrial PC (IPC) and successfully performs the monitoring of BNCT Treatment at THOR. Patients’ f BC and TPS data are also input into NeuTHORS and stored on IPC through an internal network from BC measurement room and TPS physicist. Therefore, the treatment data of each patient can be instantaneously established after each BNCT treatment for further study on BNCT. NeuTHORS can also be applied on data acquisition for a BNCT-related study, especially for animal or cell irradiation experiments. (4) Conclusions: A novel integrated platform NeuTHOR Station for monitoring BNCT clinical treatment and animal and cell irradiation study has been successfully established at THOR. With this platform, BNCT radiobiology investigations will be efficiently performed and a thorough data storage and analysis system of BNCT treatments or experiments can thus be systematically built up for the further investigation of BNCT at THOR.
Oncologists’ Knowledge, Practice and Attitude toward Fertility Preservation: A National Survey
Authors: Al Ghaithi Ahmed , Al Rashdi Eyas , Al Shukri Maryam , Al Ghabshi Rahma , Albalushi Halima
Published: March 2023

Background: Improved chemotherapy and radiotherapy treatment protocols, fortunately, increased the rates of cancer survivors over the years. However, these treatments may result in infertility or subfertility. Oncologists are considered the gateway for knowledge about cancer and its treatments’ effects. Several studies showed that many oncologists do not discuss fertility preservation with their patients. This study aimed to explore the perspective of oncologists in Oman on fertility preservation. Methods: A cross-sectional study of physicians and surgeons dealing with patients with cancer was conducted from June 2021 to December 2021. A standardized and validated questionnaire was used to collect data. Results: Participants reported that they are knowledgeable about sperm cryopreservation and gonadotropin-releasing hormone agonists use but not other methods of fertility preservation. About 94% of the participants reported that they need more knowledge about fertility preservation. More than half of the participants had never encountered cancer patients who used ovarian cryopreservation, testicular tissue cryopreservation, in vitro fertilization with embryo cryopreservation and oocyte cryopreservation. The majority (78%) agreed that discussing fertility preservation with newly diagnosed cancer patients is a high priority. Conclusions: Oncologists in Oman are supportive of fertility preservation. The lack of knowledge and unavailability of well-structured fertility preservation services in Oman hinders the initiation of fertility preservation discussions.
Contact of Rough Surfaces: An Incremental Model Accounting for Strain Gradient Plasticity
Authors: Jiang Chunyun , Yuan Weike , Zheng Yanbin , Wang Gangfeng
Published: March 2023

In the contact of rough surfaces, most contact patches are at the scale of micrometers, and thus, their contact deformation can be dominated by the size-dependent plasticity. In this paper, we propose a new strategy to analyze the role of strain gradient plasticity in the contact response between a realistic rough surface and a rigid plane, which modifies the incremental contact model based on the mechanism-based gradient plasticity (MSGP) theory. For several different rough surfaces with their topography measured experimentally, the relations between applied load and real contact area are derived in a simple but effective way. It is found that strain gradient plasticity significantly increases the level of mean contact pressure. The hardening effect caused by strain gradient plasticity weakens somewhat as the contact area increases. Compared with previous methods, the present model might be more efficient and of wider application.
New Frontiers in Parallel Robots
Authors: Shao Zhufeng , Zhang Dan , Caro Stéphane
Published: March 2023

In the field of parallel robots, marked by the birth and application of the Gough–Stewart parallel mechanism [...]
Intelligent Analysis of Construction Costs of Shield Tunneling in Complex Geological Conditions by Machine Learning Method
Authors: Ye Xiaomu , Ding Pengfei , Jin Dawei , Zhou Chuanyue , Li Yi , Zhang Jin
Published: March 2023

The estimation of construction costs for shield tunneling projects is typically based on a standard quota, which fails to consider the variation of geological parameters and often results in significant differences in unit cost. To address this issue, we propose a novel model based on a random forest machine learning procedure for analyzing the construction cost of shield tunnelling in complex geological conditions. We focus specifically on the unit consumption of grease, grouting, labor, water, and electricity. Using a dataset of geotechnical parameters and consumption quantities from a shield tunneling project, we employ KNN and correlation analysis to reduce the input dataset dimension from 17 to 6 for improved model accuracy and efficiency. Our proposed approach is applied to a shield tunneling project, with results showing that the compressive strength of geomaterial is the most influential parameter for grease, labor, water, and electricity, while it is the second most influential for grouting quantity. Based on these findings, we calculate the unit consumption and cost of the tunnelling project, which we classify into three geological categories: soil, soft rock, and hard rock. Comparing our results to the standard quota value, it is found that the unit cost of shield tunneling in soil is slightly lower (6%), while that in soft rock is very close to the standard value. However, the cost in the hard rock region is significantly greater (38%), which cannot be ignored in project budgeting. Ultimately, our results support the use of compressive strength as a classification index for shield tunneling in complex geological conditions, representing a valuable contribution to the field of tunneling cost prediction.
Refined Green–Lindsay Model for the Response of Skin Tissue under a Ramp-Type Heating
Authors: Zenkour Ashraf M. , Saeed Tareq , Alnefaie Khadijah M.
Published: March 2023

Based on Green–Lindsay generalized thermoelasticity theory, this paper presents a new refined higher-order time-derivative thermoelasticity model. Thinner one-dimensional skin tissue is considered when its inner surface is free of traction and does not show any temperature increase. The skin tissue’s bounding surface has been heated by ramp-type heating. The classical thermoelastic theories are obtained from the present general formula. The governing equations of the present model are obtained. To move the system into a space state, the Laplace transform is used. The inverse of the Laplace transform is also used with Tzuo’s method to solve the problem. As a result, the field quantities are obtained numerically, and the results of the current model are graphically represented with a comparison to two different theories of thermoelasticity. The effects of various parameters on thermomechanical waves through the skin tissue are analyzed. The theory notes a vibrational behavior in heat transfer and a different effect on the parameters discussed in this article.
Initial Experience of Robot-Assisted Transabdominal Preperitoneal (TAPP) Inguinal Hernia Repair by a Single Surgeon in South Korea
Authors: Choi Yun Suk , Kim Kyeong Deok , Choi Moon Suk , Heo Yoon Seok , Yi Jin Wook , Choe Yun-Mee
Published: March 2023

Background and Objectives: Inguinal hernia is a common surgical disease. Traditional open herniorrhaphy has been replaced by laparoscopic herniorrhaphy. Nowadays, many attempts at robotic herniorrhaphy have been reported in western countries, but there have been no reports in South Korea. The purpose of this study is to report our initial experience with robotic inguinal hernia surgery, compared to laparoscopic inguinal hernia surgery. Materials and Methods: We analyzed the clinical data from 100 patients who received inguinal hernia surgery in our hospital from November 2020 to June 2022. Fifty patients underwent laparoscopic surgery, and 50 patients underwent robotic surgery using the da Vinci Xi system. All hernia surgeries were performed by a single surgeon using the transabdominal preperitoneal (TAPP) method. Results: The mean operation time and hospital stay were not statistically different. On the first postoperative day, the visual analog scale (VAS) pain score was significantly lower in the robotic surgery group (2.9 ± 0.5 versus 2.5 ± 0.7, p = 0.015). Cumulative sum analysis revealed an approximately 12-case learning curve for robotic-assisted TAPP hernia surgery. Conclusions: Robotic-assisted TAPP inguinal hernia surgery is technically acceptable to surgeons who have performed laparoscopic inguinal hernia surgery, and the learning curve is relatively short. It is thought to be a good step toward learning other robot-assisted operations.
Design of the New Closo-Dodecarborate-Containing Gemcitabine Analogue for the Albumin-Based Theranostics Composition
Authors: Raskolupova Valeria I. , Wang Meiling , Dymova Maya A. , Petrov Gleb O. , Shchudlo Ivan M. , Taskaev Sergey Yu. , Abramova Tatyana V. , Godovikova Tatyana S. , Silnikov Vladimir N. , Popova Tatyana V.
Published: March 2023

Combination therapy is becoming an increasingly important treatment strategy because multi-drugs can maximize therapeutic effect and overcome potential mechanisms of drug resistance. A new albumin-based theranostic containing gemcitabine closo-dodecaborate analogue has been developed for combining boron neutron capture therapy (BNCT) and chemotheraphy. An exo-heterocyclic amino group of gemcitabine was used to introduce closo-dodecaborate, and a 5′-hydroxy group was used to tether maleimide moiety through an acid-labile phosphamide linker. The N-trifluoroacylated homocysteine thiolactone was used to attach the gemcitabine analogue to human serum albumin (HSA) bearing Cy5 or Cy7 fluorescent dyes. The half-maximal inhibitory concentration (IC50) of the designed theranostic relative to T98G cells was 0.47 mM with the correlation coefficient R = 0.82. BNCT experiments resulted in a decrease in the viability of T98G cells, and the survival fraction was ≈ 0.4.
A Theoretical Analysis of Interaction Energies and Intermolecular Interactions between Amphotericin B and Potential Bioconjugates Used in the Modification of Nanocarriers for Drug Delivery
Authors: Cuellar Jennifer , Parada-Díaz Lorena , Garza Jorge , Mejía Sol M.
Published: March 2023

Amphotericin B (AmB) is an antibiotic with a wide spectrum of action and low multidrug resistance, although it exhibits self-aggregation, low specificity, and solubility in aqueous media. An alternative for its oral administration is its encapsulation in polymers modified with bioconjugates. The aim of the present computational research is to determine the affinity between AmB and six bioconjugates to define which one could be more suitable. The CAM-B3LYP-D3/6-31+G(d,p) method was used for all computational calculations. The dimerization enthalpy of the most stable and abundant systems at pH = 7 allows obtaining this affinity order: AmB_1,2-distearoyl-sn-glycerol-3-phosphorylethanolamine (DSPE) > AmB_γ-cyclodextrin > AmB_DSPEc > AmB_retinol > AmB_cholesterol > AmB_dodecanol, where DSPEc is a DSPE analog. Quantum theory of atoms in molecules, the non-covalent interactions index, and natural bond orbital analysis revealed the highest abundance of noncovalent interactions for AmB-DSPE (51), about twice the number of interactions of the other dimers. Depending on the interactions’ strength and abundance of the AmB-DSPE dimer, these are classified as strong: O-H---O (2), N-H---O (3) and weak: C-H---O (25), H---H (18), C-H---C (3). Although the C-H---O hydrogen bond is weak, the number of interactions involved in all dimers cannot be underestimated. Thus, non-covalent interactions drive the stabilization of copolymers, and from our analysis, the most promising candidates for encapsulating are DSPE and γ-cyclodextrin.
Type 2 Diabetes: Also a “Clock Matter”?
Authors: Docimo Annamaria , Verde Ludovica , Barrea Luigi , Vetrani Claudia , Memoli Pasqualina , Accardo Giacomo , Colella Caterina , Nosso Gabriella , Orio Marcello , Renzullo Andrea , Savastano Silvia , Colao Annamaria , Muscogiuri Giovanna
Published: March 2023

Background: We investigated whether chronotype is associated with glycemic control, antidiabetic treatment, and risk of developing complications in patients with type 2 diabetes (T2DM). Methods: The diabetologists filled out an online questionnaire on the Google Form platform to collect the following parameters of subjects with T2DM: body mass index (BMI), fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), diabetes history, antidiabetic treatment, diabetic complications, and chronotype categories. Results: We enrolled 106 subjects with T2DM (M/F: 58/48; age: 63.3 ± 10.4 years; BMI: 28.8 ± 4.9 kg/m2). Thirty-five point eight% of the subjects showed a morning chronotype (MC), 47.2% an intermediate chronotype (IC), and 17% an evening chronotype (EC). EC subjects reported significantly higher HbA1c (p < 0.001) and FPG (p = 0.004) values, and higher prevalence of cardiovascular complications (CVC) (p = 0.028) and of subjects taking basal (p < 0.001) and rapid insulin (p = 0.01) compared to MC subjects. EC subjects reported significantly higher HbA1c (p < 0.001) and FPG (p = 0.015) than IC subjects. An inverse association was found between chronotype score, HbA1c (r = −0.459; p < 0.001), and FPG (r = −0.269; p = 0.05), remaining significant also after adjustment for BMI, age, and disease duration. Conclusions: EC is associated with higher prevalence of CVC and poorer glycemic control independently of BMI and disease duration in subjects with T2DM.
Dietary Fats and Cognitive Status in Italian Middle-Old Adults
Authors: Currenti Walter , Godos Justyna , Alanazi Amer M. , Lanza Giuseppe , Ferri Raffaele , Caraci Filippo , Grosso Giuseppe , Galvano Fabio , Castellano Sabrina
Published: March 2023

The increase in life expectancy led to a significant rise in the prevalence of age-related neurological diseases, such as cognitive impairment, dementia, and Alzheimer’s disease. Although genetics certainly play a role, nutrition emerged as a key factor in maintaining optimal cognitive function among older adults. Therefore, the study aimed to investigate whether specific categories and subcategories of dietary fats, based on carbon-chain length, are associated with cognitive status in a cohort of 883 Italian participants over the age of 50. Methods: The intake of total, single class of dietary fat, such as saturated fatty acids (SFA), monounsaturated fatty acid (MUFA), and polyunsaturated fatty acid (PUFA), and also single fatty acids grouped according to carbon-chain length, were evaluated by food frequency questionnaires (FFQs). Cognitive health was assessed using the short portable mental status questionnaire (SPMSQ). Results: After adjustment for potential confounding factors subjects with a moderate consumption of both short-chain SFA (for Q2 vs. Q1, OR = 0.23, 95% CI: 0.08, 0.66) and middle-chain SFA specifically lauric acid (C12:0) intake (for Q2 vs. Q1, OR = 0.27, 95% CI: 0.09, 0.77) were less likely to suffer from cognitive impairment. Among single MUFAs, erucic acid (C22:1) intake resulted in an inverse association, in a linear way, with cognitive impairment (for Q4 vs. Q1, OR = 0.04, 95% CI: 0.00, 0.39). Conversely, moderate intake of linoleic acid (C18:2) was associated with cognitive impairment (Q3 vs. Q1, OR = 4.59, 95% CI: 1.51, 13.94). Regarding other PUFAs, individuals consuming moderate intake alpha linolenic acid (C18:3) were less likely to have cognitive impairment (for Q3 vs. Q1, OR = 0.19, 95% CI: 0.06, 0.64). Conclusions: Total SFA intake appeared to be inversely associated with cognitive impairment. Regarding specific subtypes of fatty acids, the results mostly referred to short- and middle-chain SFA. Further studies are needed to validate the results of the present study.
Pentaclethra macroloba: A Review of the Biological, Pharmacological, Phytochemical, Cosmetic, Nutritional and Biofuel Potential of this Amazonian Plant
Authors: Nobre Lamarão Maria Louze , Ferreira Lindalva Maria de Meneses Costa , Gyles Lynch Desireé , Morais Luiz Roberto Barbosa , Silva-Júnior José Otávio Carréra , Ribeiro-Costa Roseane Maria
Published: March 2023

Pracaxi (Penthaclethra macroloba (Willd.) Kuntze) is an Amazonian plant, traditionally used by the native population to treat health disorders such as inflammation, erysipelas, wound healing, muscle pain, ear pain, diarrhea, snake and insect bites as well as for cancer treatment. Other common uses include using the oil for frying, skin and hair beautification, and as an alternative source of energy. This review is focused on highlighting its taxonomy, occurrence and botanical origins, popular uses, pharmacology and biological activities, cytotoxicity, biofuel activity and phytochemistry in order to explore future therapeutic use and other applications. Pracaxi contains triterpene saponins, sterols, tannins, oleanolic acid, unsaturated fatty acids and long-chain fatty acids, with a high behenic acid value, which may serve for incorporation into drug delivery systems as well for the development of new drugs. These components are correlated with its anti-inflammatory, antimicrobial, healing, anti-hemolytic, anti-hemorrhagic, antiophidic, and larvicidal activities against Aedes aegypti and Helicorverpa zea, which ratify the popular/traditional uses. The species is nitrogen fixing; it is easy to propagate in floodplains and the terra firma, and it can be used for the reforestation of degraded areas. Additionally, the oil extracted from the seeds can leverage the bioeconomy of the region based on sustainable exploration.