bluuebunny/crossref_metadata_2025 huggingface dataset:
An Unusual Two-Domain Thyropin from Tick Saliva: NMR Solution Structure and Highly Selective Inhibition of Cysteine Cathepsins Modulated by Glycosaminoglycans
Authors: Matoušková Zuzana , Orsághová Katarína , Srb Pavel , Pytelková Jana , Kukačka Zdeněk , Buša Michal , Hajdušek Ondřej , Šíma Radek , Fábry Milan , Novák Petr , Horn Martin , Kopáček Petr , Mareš Michael
Published: February 2024

The structure and biochemical properties of protease inhibitors from the thyropin family are poorly understood in parasites and pathogens. Here, we introduce a novel family member, Ir-thyropin (IrThy), which is secreted in the saliva of Ixodes ricinus ticks, vectors of Lyme borreliosis and tick-borne encephalitis. The IrThy molecule consists of two consecutive thyroglobulin type-1 (Tg1) domains with an unusual disulfide pattern. Recombinant IrThy was found to inhibit human host-derived cathepsin proteases with a high specificity for cathepsins V, K, and L among a wide range of screened cathepsins exhibiting diverse endo- and exopeptidase activities. Both Tg1 domains displayed inhibitory activities, but with distinct specificity profiles. We determined the spatial structure of one of the Tg1 domains by solution NMR spectroscopy and described its reactive center to elucidate the unique inhibitory specificity. Furthermore, we found that the inhibitory potency of IrThy was modulated in a complex manner by various glycosaminoglycans from host tissues. IrThy was additionally regulated by pH and proteolytic degradation. This study provides a comprehensive structure–function characterization of IrThy—the first investigated thyropin of parasite origin—and suggests its potential role in host–parasite interactions at the tick bite site.
7,8-Dihydroxy Efavirenz Is Not as Effective in CYP46A1 Activation In Vivo as Efavirenz or Its 8,14-Dihydroxy Metabolite
Authors: Mast Natalia , Li Yong , Pikuleva Irina A.
Published: February 2024

High dose (S)-efavirenz (EFV) inhibits the HIV reverse transcriptase enzyme and is used to lower HIV load. Low-dose EFV allosterically activates CYP46A1, the key enzyme for cholesterol elimination from the brain, and is investigated as a potential treatment for Alzheimer’s disease. Simultaneously, we evaluate EFV dihydroxymetabolites for in vivo brain effects to compare with those of (S)-EFV. We have already tested (rac)-8,14dihydroxy EFV on 5XFAD mice, a model of Alzheimer’s disease. Herein, we treated 5XFAD mice with (rac)-7,8dihydroxy EFV. In both sexes, the treatment modestly activated CYP46A1 in the brain and increased brain content of acetyl-CoA and acetylcholine. Male mice also showed a decrease in the brain levels of insoluble amyloid β40 peptides. However, the treatment had no effect on animal performance in different memory tasks. Thus, the overall brain effects of (rac)-7,8dihydroxy EFV were weaker than those of EFV and (rac)-8,14dihydroxy EFV and did not lead to cognitive improvements as were seen in treatments with EFV and (rac)-8,14dihydroxy EFV. An in vitro study assessing CYP46A1 activation in co-incubations with EFV and (rac)-7,8dihydroxy EFV or (rac)-8,14dihydroxy EFV was carried out and provided insight into the compound doses and ratios that could be used for in vivo co-treatments with EFV and its dihydroxymetabolite.
Untargeted Metabolomic Profiling Reveals Differentially Expressed Serum Metabolites and Pathways in Type 2 Diabetes Patients with and without Cognitive Decline: A Cross-Sectional Study
Authors: Al-Akl Neyla S. , Khalifa Olfa , Ponirakis Georgios , Parray Aijaz , Ramadan Marwan , Khan Shafi , Chandran Mani , Ayadathil Raheem , Elsotouhy Ahmed , Own Ahmed , Al Hamad Hanadi , Decock Julie , Alajez Nehad M. , Albagha Omar , Malik Rayaz A. , El-Agnaf Omar M. A. , Arredouani Abdelilah
Published: February 2024

Diabetes is recognized as a risk factor for cognitive decline, but the underlying mechanisms remain elusive. We aimed to identify the metabolic pathways altered in diabetes-associated cognitive decline (DACD) using untargeted metabolomics. We conducted liquid chromatography–mass spectrometry-based untargeted metabolomics to profile serum metabolite levels in 100 patients with type 2 diabetes (T2D) (54 without and 46 with DACD). Multivariate statistical tools were used to identify the differentially expressed metabolites (DEMs), and enrichment and pathways analyses were used to identify the signaling pathways associated with the DEMs. The receiver operating characteristic (ROC) analysis was employed to assess the diagnostic accuracy of a set of metabolites. We identified twenty DEMs, seven up- and thirteen downregulated in the DACD vs. DM group. Chemometric analysis revealed distinct clustering between the two groups. Metabolite set enrichment analysis found significant enrichment in various metabolite sets, including galactose metabolism, arginine and unsaturated fatty acid biosynthesis, citrate cycle, fructose and mannose, alanine, aspartate, and glutamate metabolism. Pathway analysis identified six significantly altered pathways, including arginine and unsaturated fatty acid biosynthesis, and the metabolism of the citrate cycle, alanine, aspartate, glutamate, a-linolenic acid, and glycerophospholipids. Classifier models with AUC-ROC > 90% were developed using individual metabolites or a combination of individual metabolites and metabolite ratios. Our study provides evidence of perturbations in multiple metabolic pathways in patients with DACD. The distinct DEMs identified in this study hold promise as diagnostic biomarkers for DACD patients.
Synthesis and Antitumor Activity Evaluation of Novel Echinatin Derivatives with a 1,3,4-Oxadiazole Moiety
Authors: Tian Xing , Sun Zihan , Zhong Ye , Yang Huali , Cheng Maosheng , Liu Yang
Published: February 2024

A series of novel echinatin derivatives with 1,3,4-oxadiazole moieties were designed and synthesized. Most of the newly synthesized compounds exhibited moderate antiproliferative activity against the four cancer cell lines. Notably, Compound T4 demonstrated the most potent activity, with IC50 values ranging from 1.71 µM to 8.60 µM against the four cancer cell lines. Cell colony formation and wound healing assays demonstrated that T4 significantly inhibited cell proliferation and inhibited migration. We discovered that T4 exhibited moderate binding affinity with the c-KIT protein through reverse docking. The results were effectively validated through subsequent molecular docking and c-KIT enzyme activity assays. In addition, Western blot analysis revealed that T4 inhibits the phosphorylation of downstream proteins of c-KIT. The results provide valuable inspiration for exploring novel insights into the design of echinatin-related hybrids as well as their potential application as c-KIT inhibitors to enhance the efficacy of candidates.
Analysis of the Model of Atherosclerosis Formation in Pig Hearts as a Result of Impaired Activity of DNA Repair Enzymes
Authors: Paslawski Robert , Kowalczyk Paweł , Paslawska Urszula , Wiśniewski Jerzy , Dzięgiel Piotr , Janiszewski Adrian , Kiczak Liliana , Zacharski Maciej , Gawdzik Barbara , Kramkowski Karol , Szuba Andrzej
Published: February 2024

Excessive consumption of food rich in saturated fatty acids and carbohydrates can lead to metabolic disturbances and cardiovascular disease. Hyperlipidemia is a significant risk factor for acute cardiac events due to its association with oxidative stress. This leads to arterial wall remodeling, including an increase in the thickness of the intima media complex (IMT), and endothelial dysfunction leading to plaque formation. The decreased nitric oxide synthesis and accumulation of lipids in the wall result in a reduction in the vasodilating potential of the vessel. This study aimed to establish a clear relationship between markers of endothelial dysfunction and the activity of repair enzymes in cardiac tissue from a pig model of early atherosclerosis. The study was conducted on 28 female Polish Landrace pigs, weighing 40 kg (approximately 3.5 months old), which were divided into three groups. The control group (n = 11) was fed a standard, commercial, balanced diet (BDG) for 12 months. The second group (n = 9) was fed an unbalanced, high-calorie Western-type diet (UDG). The third group (n = 8) was fed a Western-type diet for nine months and then switched to a standard, balanced diet (regression group, RG). Control examinations, including blood and urine sampling, were conducted every three months under identical conditions with food restriction for 12 h and water restriction for four hours before general anesthesia. The study analyzed markers of oxidative stress formed during lipid peroxidation processes, including etheno DNA adducts, ADMA, and NEFA. These markers play a crucial role in reactive oxygen species analysis in ischemia–reperfusion and atherosclerosis in mammalian tissue. Essential genes involved in oxidative-stress-induced DNA demethylation like OGG1 (8-oxoguanine DNA glycosylase), MPG (N-Methylpurine DNA Glycosylase), TDG (Thymine-DNA glycosylase), APEX (apurinic/apirymidinic endodeoxyribonuclease 1), PTGS2 (prostaglandin-endoperoxide synthase 2), and ALOX (Arachidonate Lipoxygenase) were measured using the Real-Time RT-PCR method. The data suggest that high oxidative stress, as indicated by TBARS levels, is associated with high levels of DNA repair enzymes and depends on the expression of genes involved in the repair pathway. In all analyzed groups of heart tissue homogenates, the highest enzyme activity and gene expression values were observed for the OGG1 protein recognizing the modified 8oxoG. Conclusion: With the long-term use of an unbalanced diet, the levels of all DNA repair genes are increased, especially (significantly) Apex, Alox, and Ptgs, which strongly supports the hypothesis that an unbalanced diet induces oxidative stress that deregulates DNA repair mechanisms and may contribute to genome instability and tissue damage.
CD163-Mediated Small-Vessel Injury in Alzheimer’s Disease: An Exploration from Neuroimaging to Transcriptomics
Authors: Chen Yuewei , Lu Peiwen , Wu Shengju , Yang Jie , Liu Wanwan , Zhang Zhijun , Xu Qun
Published: February 2024

Patients with Alzheimer’s disease (AD) often present with imaging features indicative of small-vessel injury, among which, white-matter hyperintensities (WMHs) are the most prevalent. However, the underlying mechanism of the association between AD and small-vessel injury is still obscure. The aim of this study is to investigate the mechanism of small-vessel injury in AD. Differential gene expression analyses were conducted to identify the genes related to WMHs separately in mild cognitive impairment (MCI) and cognitively normal (CN) subjects from the ADNI database. The WMH-related genes identified in patients with MCI were considered to be associated with small-vessel injury in early AD. Functional enrichment analyses and a protein–protein interaction (PPI) network were performed to explore the pathway and hub genes related to the mechanism of small-vessel injury in MCI. Subsequently, the Boruta algorithm and support vector machine recursive feature elimination (SVM-RFE) algorithm were performed to identify feature-selection genes. Finally, the mechanism of small-vessel injury was analyzed in MCI from the immunological perspectives; the relationship of feature-selection genes with various immune cells and neuroimaging indices were also explored. Furthermore, 5×FAD mice were used to demonstrate the genes related to small-vessel injury. The results of the logistic regression analyses suggested that WMHs significantly contributed to MCI, the early stage of AD. A total of 276 genes were determined as WMH-related genes in patients with MCI, while 203 WMH-related genes were obtained in CN patients. Among them, only 15 genes overlapped and were thus identified as the crosstalk genes. By employing the Boruta and SVM-RFE algorithms, CD163, ALDH3B1, MIR22HG, DTX2, FOLR2, ALDH2, and ZNF23 were recognized as the feature-selection genes linked to small-vessel injury in MCI. After considering the results from the PPI network, CD163 was finally determined as the critical WMH-related gene in MCI. The expression of CD163 was correlated with fractional anisotropy (FA) values in regions that are vulnerable to small-vessel injury in AD. The immunostaining and RT-qPCR results from the verifying experiments demonstrated that the indicators of small-vessel injury presented in the cortical tissue of 5×FAD mice and related to the upregulation of CD163 expression. CD163 may be the most pivotal candidates related to small-vessel injury in early AD.
Blue Light Attracts More Spodoptera frugiperda Moths and Promotes Their Flight Speed
Authors: Yang Haibo , Lu Jing , Zhu Pinhong , Sun Yalan , Hu Zhenjie , Li Dingxu , Huang Jianrong
Published: February 2024

Light traps are a useful method for monitoring and controlling the important migratory pest, the fall armyworm, Spodoptera frugiperda. Studies have shown that S. frugiperda is sensitive to blue, green, or ultraviolet (UV) light, but the conclusions are inconsistent. Furthermore, conventional black light traps are less effective for trapping S. frugiperda. To improve the trapping efficiency of this pest, it is crucial to determine the specific wavelength to which S. frugiperda is sensitive and measure its flight capability under that wavelength. This study investigated the effects of light wavelength on the phototaxis and flight performance of S. frugiperda. The results showed that blue light was the most sensitive wavelength among the three different LED lights and was unaffected by gender. The flight capability of S. frugiperda varied significantly in different light conditions, especially for flight speed. The fastest flight speed was observed in blue light, whereas the slowest was observed in UV light compared to dark conditions. During a 12 h flight period, speed declined more rapidly in blue light and more slowly in UV, whereas speed remained stable in dark conditions. Meanwhile, the proportion of fast-flying individuals was highest under blue light, which was significantly higher than under UV light. Therefore, the use of light traps equipped with blue LED lights can improve the trapping efficiency of S. frugiperda. These results also provide insights for further research on the effects of light pollution on migratory insects.
Metabolically Abnormal Non-Obese Phenotype Is Significantly Associated with All-Cause Mortality in Hemodialysis Patients
Authors: Lee Jin Hyeog , Yun Hae-Ryong , Kim Hyung Woo , Park Jung Tak , Han Seung Hyeok , Kim Yong-Lim , Kim Yon Su , Yang Chul Woo , Kim Nam-Ho , Kang Shin-Wook , Yoo Tae-Hyun
Published: February 2024

The association between obesity and all-cause mortality in patients undergoing kidney failure with replacement therapy (KFRT) has shown conflicting results. This study aimed to evaluate whether metabolic abnormalities (MA) increase the risk of all-cause mortality in these patients. Between 2009 and 2015, 1141 patients undergoing KFRT were recruited from the Clinical Research Center for End-Stage Renal Disease dataset. Patients were divided into four groups according to the presence of obesity and MA. Multivariate Cox proportional hazard analysis was performed to determine the association between the phenotypes and all-cause mortality. During a mean follow-up of 4.2 years, all-cause mortality was observed in 491 (43.0%) patients. Obesity had a 24% decreased risk of all-cause mortality compared with non-obesity. In contrast, the presence of MA showed a 1.53-fold increased risk of all-cause mortality. There was a significant interaction between obesity and MA (p = 0.006). In Cox proportional hazard analyses after adjustment of confounding factors, the metabolically abnormal non-obesity (MANO) phenotype showed a 1.63-fold increased risk of all-cause mortality compared with the metabolically healthy non-obesity phenotype. In subgroup analysis, the risk of all-cause mortality was higher in the MANO phenotype; this phenotype was significantly associated with a higher all-cause mortality in patients undergoing KFRT.
Orthodontic Pain and Dietary Impact Considering Age Groups: A Comparative Study
Authors: Negruțiu Bianca-Maria , Vaida Luminița Ligia , Judea-Pusta Claudia , Romanec Cristian , Moca Abel Emanuel , Costea Cristina Paula , Staniș Claudia-Elena , Rus Marius
Published: February 2024

(1) Background: orthodontic treatment can frequently be associated with discomfort and pain, a significant factor contributing to treatment discontinuation. (2) Methods: This study, conducted on 160 orthodontic patients across different age groups, aimed to explore the influence of age on patients’ responses to treatment, particularly regarding changes in dietary patterns and weight loss. The patients were categorized into three age groups and assessed through a questionnaire about pain perception, pain latency, dietary changes, and weight loss associated with orthodontic appliances. (3) Results: Younger patients (6–12 years) reported lower pain levels, shorter pain latency and fewer alterations in dietary habits compared to adults (over 18 years). Females over 18 represented a significant portion of the sample, suggesting a self-driven inclination towards orthodontic treatment for aesthetic reasons. Fixed orthodontic appliances induced more significant pain than removable ones. Adults experienced more changes in dietary habits and weight loss than younger individuals. (4) Conclusions: the results provide valuable insights for orthodontic practitioners aiming to mitigate adverse effects and improve overall patient experience during treatment.
The Status of Fertility Preservation (FP) Insurance Mandates and Their Impact on Utilization and Access to Care
Authors: Sauerbrun-Cutler May-Tal , Rollo Allegra , Gadson Alexis , Eaton Jennifer L.
Published: February 2024

Fertility preservation (FP) is the use of a specific medical intervention to protect the fertility of individuals whose disease or disease treatment may lead to infertility. These medical interventions include the cryopreservation of oocytes, embryos, ovarian tissue, sperm, and testicular tissue; oocyte and embryo cryopreservation are the most widely used interventions in the United States. Although guidelines recommend FP prior to undergoing gonadotoxic treatments, cost barriers are high. For example, the average cost of an oocyte cryopreservation cycle in the United States exceeds $10,000. High cost and lack of insurance coverage are two of the most cited reasons explaining the low Reproductive Endocrinology and Infertility (REI) referral rates and limited FP utilization. Broadening insurance mandates for FP prior to gonadotoxic treatments could improve utilization and provide cancer survivors with improved quality of life post treatment.
Structure-Function Correlation of Retinal Fibrosis in Eyes with Neovascular Age-Related Macular Degeneration
Authors: Schranz Markus , Sacu Stefan , Reiter Gregor S. , Baratsits Magdalena , Desissaire Silvia , Pircher Michael , Mylonas Georgios , Hitzenberger Christoph , Schmidt-Erfurth Ursula , Roberts Philipp Ken
Published: February 2024

Purpose: To assess retinal function in areas of presumed fibrosis due to neovascular age-related macular degeneration (nAMD), using multimodal imaging and structure-function correlation. Design: Cross-sectional observational study. Methods: 30 eyes of 30 consecutive patients with nAMD with a minimum history of one year of anti-vascular endothelial growth factor therapy were included. Each patient underwent microperimetry (MP), color fundus photography (CFP), standard spectral-domain-based OCT (SD-OCT), and polarization sensitive-OCT (PS-OCT) imaging. PS-OCT technology can depict retinal fibrosis based on its birefringence. CFP, SD-OCT, and PS-OCT were evaluated independently for the presence of fibrosis at the corresponding MP stimuli locations. MP results and morphologic findings in CFP, SD-OCT, and PS-OCT were co-registered and analyzed using mixed linear models. Results: In total, 1350 MP locations were evaluated to assess the functional impact of fibrosis according to a standardized protocol. The estimated means of retinal areas with signs of fibrosis were 12.60 db (95% confidence interval: 10.44–14.76) in CFP, 11.60 db (95% COI: 8.84–14.36) in OCT, and 11.02 db (95% COI 8.10–13.94) in PS-OCT. Areas evaluated as subretinal fibrosis in three (7.2 db) or two (10.1 db) modalities were significantly correlated with a lower retinal sensitivity than a subretinal fibrosis observed in only one (15.3 db) or none (23.3 db) modality (p < 0.001). Conclusions: CFP, SD-OCT and PS-OCT are all suited to detect areas of reduced retinal sensitivity related to fibrosis, however, a multimodal imaging approach provides higher accuracy in the identification of areas with low sensitivity in MP (i.e., impaired retinal function), and thereby improves the detection rate of subretinal fibrosis in nAMD.
Characteristic Differences between Normotensive and Hypertensive Pseudoexfoliative Glaucoma
Authors: Shin Da Young , Park Chan Kee , Lee Na Young
Published: February 2024

Purpose: To compare the differences between eyes with pseudoexfoliative glaucoma (PXG) when they are divided into two groups (hypertensive PXG and normotensive PXG) according to the intraocular pressure (IOP). Methods: This is a retrospective study. Data from 86 hypertensive PXG eyes and 80 normotensive PXG eyes were included. Hypertensive PXG was defined as PXG with IOP ≥ 22 mmHg, and normotensive PXG was defined as with IOP ≤ 21 mmHg). Central corneal thickness (CCT) was measured by ultrasound pachymetry. Lamina cribrosa thickness (LT) was evaluated using swept-source optical coherence tomography. Results: No significant differences were observed between hypertensive and normotensive PXG in terms of age, gender, axial length, hypertension, or diabetes. Normotensive PXG eyes had thinner CCT than hypertensive PXG eyes (p = 0.02). To compare LT, a sub-analysis was performed after matching age, VF MD and retinal nerve fiber layer thickness. The normotensive PXG group (n = 32) demonstrated significantly thinner LT compared with the hypertensive PXG group (n = 32) at similar ages and levels of glaucoma severity (p < 0.001). Conclusions: Eyes with normotensive PXG demonstrated thinner CCT and LT compared with those with hypertensive PXG, suggesting structural vulnerability to glaucoma.
Aging with a Liver Graft: Analysis of Very Long-Term Survivors after Liver Transplantation
Authors: De Simone Paolo , Bronzoni Jessica , Martinelli Caterina , Ducci Juri , Campani Daniela , Gitto Stefano , Marchetti Piero , Biancofiore Giandomenico
Published: February 2024

Background: In Italy, data on long-term survivors after liver transplantation are lacking. Materials and Methods: We conducted a hybrid design study on a cohort of 359 adult recipients who received transplants between 1996 and 2002 to identify predictors of survival and the prevalence of co-morbidities among long-term survivors. Results: The actuarial (95% CI) patient survival was 96% (94.6–98.3%), 69% (64.2–73.6%), 55% (49.8–59.9%), 42.8% (37.6–47.8%), and 34% (29.2–38.9%) at 1, 5, 10, 15, and 20 years, respectively. The leading causes of death were hepatitis C virus recurrence (24.6%), extrahepatic malignancies (16.9%), infection (14.4%), and hepatocellular carcinoma recurrence (14.4%). The factors associated with the survival probability were younger donor and recipient ages (p = 0.001 and 0.004, respectively), female recipient sex (p < 0.001), absence of HCV (p < 0.01), absence of HCC (p = 0.001), and absence of diabetes mellitus at one year (p < 0.01). At the latest follow-up, the leading comorbidities were hypertension (53.6%), obesity (18.7%), diabetes mellitus (17.1%), hyperlipidemia (14.7%), chronic kidney dysfunction (14.7%), and extrahepatic malignancies (13.8%), with 73.9% of patients having more than one complication. Conclusions: Aging with a liver graft is associated with an increased risk of complications and requires ongoing care to reduce the long-term attrition rate resulting from chronic immunosuppression.
Learning Curve for Starting a Successful Single-Centre TAVR Programme with Multiple Devices: Early and Mid-Term Follow-Up
Authors: Magyari Balázs , Kittka Bálint , Goják Ilona , Schönfeld Kristóf , Szapáry László Botond , Simon Mihály , Kiss Rudolf , Bertalan Andrea , Várady Edit , Gyimesi András , Szokodi István , Horváth Iván Gábor
Published: February 2024

Aims: We report 30-day, 1-year, and 3-year outcomes for a new TAVR programme that used five different transcatheter heart valve (THV) systems. Methods: From 2014 to 2020, 122 consecutive patients with severe aortic stenosis (AS) received TAVR based on the Heart Team decision. Outcomes were analysed for the whole study population and in addition the first 63 patients (Cohort A, 2014 to 2019) were compared to the last 59 patients (Cohort B, 2019 to 2020). Outcomes included VARC-2 definitions and device performance assessed via transthoracic echocardiography by independent high-volume investigators. Results: The mean patient age was 77.9 ± 6.1 years old, and 48 (39.3%) were male. The mean logistic Euroscore II was 4.2 ± 4.5, and the mean STS score was 6.9 ± 4.68. The systems used were as follows: Medtronic Corevalve Evolute R/PRO (82 patients—67.2%); Abbott Portico (13—10.6%); Boston Scientific Lotus (10—8.2%); Meril Myval (11—9%); and Boston Scientific Neo Accurate (6—5%). Access was transfemoral (95.9% of patients); surgical cut down (18% vs. percutaneous 77.8%); subclavian (n = 2); trans-axillary (n = 2); and direct aorta (n = 1). VARC-2 outcomes were as follows: device success rate 97.5%; stroke rate 1.6%; major vascular complication 3.3%; permanent pacemaker implantation 12.4%. At discharge, the incidences of grade I and II aortic regurgitation were 39.95 and 55.5%, respectively. At one year, all-cause mortality was 7.4% without admissions for valve-related dysfunction. The 3-year all-cause mortality and all-stroke rates were 22.9% and 4.1%, respectively. Between the 1-year and 3-year follow-ups, valve-related dysfunction was detected in three patients; one had THV system endocarditis that led to death. There was a remarkable but statistically non-significant decrease in mortality from Cohort A to Cohort B [four (6.3%) vs. one patient (1.7%), p = 0.195] and major vascular complications occurred at a significantly higher rate in the Cohort B [zero (0%) vs. four (6.8% patient, p = 0.036)]. Overall, we found that using multiple devices was safe and allowed for a learning team to achieve a high device success rate from the beginning (97.5%). Conclusions: TAVR with different THV systems showed acceptable early and mid-term outcomes for survival, technical success, and valve-related adverse events in high-risk patients with significant AS, even in the learning curve phase.
The Role of Quantified Parameters on River Plume Structure: Numerical Simulation
Authors: Zhang Jiaxin , Hong Kan , Yuan Yeping , Lin Ying-Tien , Han Dongrui
Published: February 2024

A three-dimensional numerical model was established with OpenFOAM-5.x to investigate plume characteristics under windless and rainless weather conditions. The large eddy simulation was applied, combined with a modified solver for solving governing equations with the Boussinesq approximation in a single rotating frame. The relationship between plume characteristics (e.g., gradient Richardson number and maximum plume width) and quantified parameters (e.g., rotation period, shelf slope, and reduced gravity) was analyzed progressively. The results show the model can reproduce the change in plume types and instability found in the laboratory experiments. With the increase in the rotation period, river plumes change from a surface-advected type to a bottom-attached type. The outline of the plume bulge accurately delineates the external region where the gradient Richardson number is less than 0.25, as well as the region near the wall. When the shelf slope approaches 0, the offshore movement becomes stronger while the alongshore coastal current comes into being with a delay associated with the slope and the rotation period. Compared with the extremely gentle slope case and the steep slope case, the maximum width in the gentle slope case changes significantly at about 1.5 rotation periods. Greater reduced gravity does promote offshore propagation, especially near the surface.
Argo Buoy Trajectory Prediction: Multi-Scale Ocean Driving Factors and Time–Space Attention Mechanism
Authors: Ning Pengfei , Zhang Dianjun , Zhang Xuefeng , Zhang Jianhui , Liu Yulong , Jiang Xiaoyi , Zhang Yansheng
Published: February 2024

The Array for Real-time Geostrophic Oceanography (Argo) program provides valuable data for maritime research and rescue operations. This paper is based on Argo historical and satellite observations, and inverted sea surface and submarine drift trajectories. A neural network method was developed to predict the position of Argo buoys, improving target tracking and emergency support capabilities. Based on a deep learning framework using a Simple Recurrent Unit (SRU), a new Time–Space Feature Fusion Method based on an Attention Mechanism (TSFFAM) model was constructed. The TSFFAM mechanism can predict the target trajectory more accurately, avoiding the disadvantages of traditional Long Short-Term Memory (LSTM) models, which are time consuming and difficult to train. The TSFFAM model is able to better capture multi-scale ocean factors, leading to more accurate and efficient buoy trajectory predictions. In addition, it aims to shed light on the mechanism of the joint multi-element and multi-scale effects of laminar and surface currents on multi-scale ocean factors, thereby deepening our understanding of the multi-element and multi-scale interactions in different spatio-temporal regimes of the ocean. Experimental verification was conducted in the Pacific Ocean using buoy trajectory data, and the experimental results showed that the buoy trajectory prediction models proposed in this paper can achieve high prediction accuracy, with the TSFFAM model improving the accuracy rate by approximately 20%. This research holds significant practical value for the field of maritime studies, precise rescue operations, and efficient target tracking.
Assessment of Hydrodynamic Performance and Motion Suppression of Tension Leg Floating Platform Based on Tuned Liquid Multi-Column Damper
Authors: Cui Fuyin , Chen Shuling , Hao Hongbin , Han Changzhi , Ni Ruidong , Zhuo Yueyue
Published: February 2024

To address the unstable motion of a tension leg platform (TLP) for floating wind turbines in various sea conditions, an improved method of incorporating a tuned liquid multi-column damper (TLMCD) into the TLP foundation is proposed. In order to evaluate the control effect of TLMCD on the motion response of the floating foundation, a multiphase flow solver based on a viscous flow CFD method and overlapping grid technique is applied to model the coupled multi-body dynamics interaction problem involving liquid tanks, waves, and a spring mooring system. This method has been proven to accurately capture the high-frequency motions of the structure and account for complex viscous interferences affecting the geometric motions. Additionally, the volume of fluid (VOF) method and the first-order linear superposition method are used to model the focused wave, enabling a simulation of the effects of transient wave loads on the floating foundation. The results show that the tuned damping effect of TLMCD on the TLP is mainly in the pitch motion, with the maximum pitch amplitude control volume ratio of TLMCD reaching up to 86% and the maximum surge amplitude control volume ratio of TLMCD reaching up to 25.2% under the operating conditions. These findings highlight the potential for additional research on and implementation of TLMCD technology.
Inhibitory Effect of L-Methionine on Alternaria alternata Based on Metabolomics Analysis
Authors: Zhu Xianran , Zhang Shaoying , Yu Youwei , Li Shengwang , Yang Chao , Chang Yuan
Published: February 2024

Alternaria alternata is the main pathogenic fungus of postharvest black spots in fruits and vegetables. This study aimed to explore the antifungal activity of methionine on A. alternata in vitro and to reveal related antifungal mechanisms through a metabolomics analysis. The results showed that the inhibitory effects of L-methionine (Met) treatment on mycelium growth, spore germination, and the germ tube elongation of A. alternata were enhanced with an increase in the Met concentration, but the inhibitory effects decreased when the Met concentration was higher than 50 mmolL−1. The results of propidium iodide staining and scanning electron microscopy showed that the Met treatment damaged the plasma membrane integrity of the A. alternata spores and caused an irreversible deformation of mycelium. In addition, after the Met treatment, the leakage of electrolytes, nucleic acid, and proteins in the A. alternata cells was significantly higher than that in the control group, indicating that the Met treatment increased the permeability of the cell membranes. Eighty-one different metabolites, divided into seven categories, were identified through the metabolomics analysis, including forty-three downregulated metabolites and thirty-eight upregulated metabolites. Among them, these differential metabolites were mainly involved in amino acid synthesis and metabolism, the pentose phosphate pathway, and the TCA cycle. Therefore, the antifungal effect of the Met treatment on A. alternata was mainly to damage the integrity of the cell membranes, make nucleic acid and protein contents leak, and affect the TCA cycle, carbohydrate metabolism, amino acid synthesis metabolism, and the metabolic pathways associated with cell membrane biosynthesis. Thus, the growth and development of A. alternata were inhibited. The research enriched the investigation of the effect of the antifungal mechanism of Met treatment on A. alternata and provided a theoretical basis for the application of Met to prevent and treat postharvest black spots in fruits and vegetables.
Influence of Salinity on the Extracellular Enzymatic Activities of Marine Pelagic Fungi
Authors: Salazar-Alekseyeva Katherine , Herndl Gerhard J. , Baltar Federico
Published: February 2024

Even though fungi are ubiquitous in the biosphere, the ecological knowledge of marine fungi remains rather rudimentary. Also, little is known about their tolerance to salinity and how it influences their activities. Extracellular enzymatic activities (EEAs) are widely used to determine heterotrophic microbes’ enzymatic capabilities and substrate preferences. Five marine fungal species belonging to the most abundant pelagic phyla (Ascomycota and Basidiomycota) were grown under non-saline and saline conditions (0 g/L and 35 g/L, respectively). Due to their sensitivity and specificity, fluorogenic substrate analogues were used to determine hydrolytic activity on carbohydrates (β-glucosidase, β-xylosidase, and N-acetyl-β-D-glucosaminidase); peptides (leucine aminopeptidase and trypsin); lipids (lipase); organic phosphorus (alkaline phosphatase), and sulfur compounds (sulfatase). Afterwards, kinetic parameters such as maximum velocity (Vmax) and half-saturation constant (Km) were calculated. All fungal species investigated cleaved these substrates, but some species were more efficient than others. Moreover, most enzymatic activities were reduced in the saline medium, with some exceptions like sulfatase. In non-saline conditions, the average Vmax ranged between 208.5 to 0.02 μmol/g biomass/h, and in saline conditions, 88.4 to 0.02 μmol/g biomass/h. The average Km ranged between 1553.2 and 0.02 μM with no clear influence of salinity. Taken together, our results highlight a potential tolerance of marine fungi to freshwater conditions and indicate that changes in salinity (due to freshwater input or evaporation) might impact their enzymatic activities spectrum and, therefore, their contribution to the oceanic elemental cycles.
On Smoothing and Habit Formation of Variable Life Annuity Benefits
Authors: Steffensen Mogens , Vikkelsøe Savannah Halling
Published: February 2024

This paper studies optimal consumption and investment strategies with lifetime uncertainty to design a smooth pension product. In a simplified Black–Scholes market, we investigate three strategies for consumption and investment: the classical strategy, the habit strategy, and the hybrid strategy. Incorporating additive habit formation in preferences leads to a request for less consumption volatility. Studying the consumption dynamics, it turns out that the hybrid strategy complies with the same preferences as the habit strategy. In our design of a smooth pension product, we are highly inspired by the consumption structure under the hybrid strategy and let consumption be specified as a time-dependent weighted average of last year’s consumption level and a standard market rate life annuity. We give two approaches for the investment portfolio. The numerical examples show that consumption under these approaches is less volatile than consumption under the classical strategy.
Multi-Scenario Simulation of Ecosystems Based on Adaptive Restoration to Promote Human–Nature Harmony: A Case Study of Loess Hills Micro-Watershed
Authors: Li Qiang , Shi Xueyi , Zhao Zhongqiu , Wu Qingqing
Published: February 2024

The ecological environment in loess hilly regions is fragile, and the contradiction between the development of human society and ecological environment protection is becoming more and more prominent with the intensification of human interference. In order to give full play to the role of ecosystem adaptation in ecological restoration, this study seeks natural conditions that are suitable for the stable existence of ecosystems in the Wanhuigou catchment using the reference ecosystem method and uses these conditions as constraints of the GeoSOS-FLUS model for multi-scenario simulation. Based on ecosystem service value and ecological compensation mechanisms, the comprehensive benefits of different scenarios are compared, and economic development is taken into account while ensuring that ecological protection remains a priority. The results show the following: (1) The unstable ecosystems concentrated on a gentle slope (5–15°) at altitudes of 1201–1379 m, 1201–1594 m, 1379–1715 m and 1715–1856 m are suitable for restoration to farmland, shrub, grassland and forest ecosystems, respectively, and the change characteristics of soil and vegetation communities also verify the above conclusions. (2) The scenario of agricultural development from 2020 to 2030 and the early stages from 2030 to 2050 is the best among the three scenarios, while the scenario of ecological protection is the best in the middle and late stages of 2030–2050. Formulating relevant policies and ecological protection measures according to the scenario of ecological protection is more conducive to promoting the harmonious coexistence of humans and nature. (3) Under the scenario of ecological protection, the unstable ecosystem distributed along the gentle slope (5–15°) of 1379–1483 m and 1483–1594 m achieves the most significant improvement in ecosystem service value by focusing on and giving priority to the restoration of natural conditions that are suitable for the stable existence of ecosystems. This study provides ideas and references for the formation of ecosystem restoration and development strategies for small watersheds in loess hilly regions, and it is of great significance for the promotion of a harmonious coexistence between humans and nature.
A Comparative Evaluation of Ecosystem Services Provided by Street Trees in Seoul for the Suggestion of Social Equity
Authors: Choi Yongwan , Machado Jessica , Kim Gunwoo
Published: February 2024

Cities must overcome their limitations on quantitative growth by pursuing sustainable development. Road-centered development leads to social problems, including inequality, during urban expansion. This study focuses on quantifying the ecosystem services provided by street trees in the Gangnam and Gangbuk Districts of Seoul, South Korea. This research utilized public data and field surveys conducted between April and August 2023, which is the best time to grow coniferous and deciduous trees. The results helped quantify the improvement in the air quality and ecological economic value from the perspective of plant species structure and carbon storage. The street trees in Gangnam stored 3691.61 t (metric tons) and sequestered 359.45 t of carbon; removed 2.28 t of air pollutants; and reduced 3977.46 m3 of rainwater runoff annually. In contrast, the street trees in Gangbuk stored 831.61 t and sequestered 74.97 t of carbon; removed 0.4 t of air pollutants; and annually reduced rainwater runoff by 1491.74 m3. By quantifying the ecosystem services of street trees, this study showed a gap in the supply of ecosystem services, which are relatively poor in economically poor areas, thus contributing to a more holistic understanding of urban growth and advocating for inclusive and socially equitable development strategies and management policies in Seoul.
Acoustic Similarity Predicts Vowel Phoneme Detection in an Unfamiliar Regional Accent: Evidence from Monolinguals, Bilinguals and Second-Language Learners
Authors: Williams Daniel , Ağabeyoğlu Turgut , Gafos Adamantios , Escudero Paola
Published: February 2024

When encountering an unfamiliar accent, a hypothesized perceptual challenge is associating its phonetic realizations with the intended phonemic categories. Greater accumulated exposure to the language might afford richer representations of phonetic variants, thereby increasing the chance of detecting unfamiliar accent speakers’ intended phonemes. The present study examined the extent to which the detection of vowel phonemes spoken in an unfamiliar regional accent of English is facilitated or hindered depending on their acoustic similarity to vowels produced in a familiar accent. Monolinguals, experienced bilinguals and native German second-language (L2) learners completed a phoneme detection task. Based on duration and formant trajectory information, unfamiliar accent speakers’ vowels were classed as acoustically “similar” or “dissimilar” to counterpart phonemes in the familiar accent. All three participant groups were substantially less sensitive to the phonemic identities of “dissimilar” compared to “similar” vowels. Unlike monolinguals and bilinguals, L2 learners showed a response shift for “dissimilar” vowels, reflecting a cautious approach to these items. Monolinguals displayed somewhat heightened sensitivity compared to bilinguals, suggesting that greater accumulated exposure aided phoneme detection for both “similar” and “dissimilar” vowels. Overall, acoustic similarity predicted the relative success of detecting vowel phonemes in cross-dialectal speech perception across groups with varied linguistic backgrounds.
Spontaneous Intracranial Hypotension and Subdural Hematomas Treatment Management Using MMA Embolization and Target Blood Patch: A Case Report
Authors: Cirillo Luigi , Verna Francesca , Princiotta Ciro , Dall’Olio Massimo , Rustici Arianna , Bortolotti Carlo , Badaloni Filippo , Mascarella Davide , Cortelli Pietro , Cevoli Sabina
Published: February 2024

We report a patient suffering from spontaneous intracranial hypotension (SIH) who, following a non-selective lumbar blood patch, returned to his healthcare provider with severe symptoms of neurological deficits. It was subsequently discovered that the aforementioned deficits were due to a bilateral subdural hematoma, and an emergency surgical drainage of the hematoma has been performed. However, the hematoma reformed and potential cerebrospinal fluid leakage was consequently investigated through myelography. Following the diagnostic finding of a venous diverticulum, a selective blood patch was executed in the affected area, and in order to stabilize the hematoma, an embolization of the middle meningeal arteries was performed. The combination of such operations allowed for the resorption of the hematoma and the improvement of neurological symptoms.
Herbal- and Dietary-Supplement-Induced Liver Injury: A Review of the Recent Literature
Authors: Patel-Rodrigues Palak A. , Cundra Lindsey , Alhaqqan Dalal , Gildea Daniel T. , Woo Stephanie M. , Lewis James H.
Published: February 2024

Herbal-induced liver injury (HILI) continues to increase in prevalence each year due to the ongoing popularity of herbal supplements and complementary and alternative medicines. A detailed literature review of case reports and clinical studies published from March 2021 to March 2023 was performed. We discuss the epidemiology and diagnosis of HILI as well as the current and proposed laws and regulations. The 2021 ACG guidelines and 2022 AASLD practice guidelines for the diagnosis and management of drug and herbal-induced liver injury are discussed. We describe updates to previously reported etiologies of HILI such as ayurveda, ashwagandha, turmeric, kratom, green tea extract, and garcinia cambogia. Newly described supplements resulting in HILI, such as tinospora cordifolia, horse chestnut, alkaline water, and more, are described. We discuss newly and previously identified hepatoprotective herbal supplements as they have been reported in the study of animal models and human liver cells. This review suggests the need for ongoing research on the causes and mechanisms of HILI to ensure its proper diagnosis, prevention, and treatment in the future. The goal of this review is to provide novice and expert readers with knowledge regarding the possible etiologies of HILI and a general overview.
Effect of Graphene Nanoplatelet Content on Mechanical and Elevated-Temperature Tribological Performance of Self-Lubricating ZE10 Magnesium Alloy Nanocomposites
Authors: Kandemir Sinan , Yöyler Sibel , Kumar Rahul , Antonov Maksim , Dieringa Hajo
Published: February 2024

Magnesium (Mg) and graphene in alloy formulations are of paramount importance for lightweight engineering applications. In the present study, ZE10 Mg-alloy-based nanocomposites reinforced with graphene nanoplatelets (GNPs) having a thickness of 10–20 nm were fabricated via ultrasound-assisted stir casting. The effect of GNP contents (0.25, 0.5, and 1.0 wt.%) on the microstructure, Vickers hardness, and tensile properties of nanocomposites was investigated. Further, tribological studies were performed under a ball-on-disc sliding wear configuration against a bearing ball counterbody, at room and elevated temperatures of 100 °C and 200 °C, to comprehend temperature-induced wear mechanisms and friction evolution. It was revealed that the GNP addition resulted in grain coarsening and increased porosity rate of the Mg alloy. While the composites exhibited improved hardness by 20–35% at room temperature and 100 °C, a minor change was observed in their hardness and tensile yield strength values at 200 °C with respect to the GNP-free alloy. A notable improvement in lowering and stabilizing friction (coefficient of friction at 200 °C~0.25) and wear values was seen for the self-lubricating GNP-added composites at all sliding temperatures. The worn surface morphology indicated a simultaneous occurrence of abrasive and adhesive wear mode in all samples at room temperature and 100 °C, while delamination and smearing along with debris compaction (tribolayer protection) were the dominant mechanisms of wear at 200 °C. Inclusively, the results advocate steady frictional conditions, improved wear resistance, and favorable wear-protective mechanisms for the Mg alloy–GNP nanocomposites at room and elevated temperatures.
Phase Equilibria Related to NiGa5 in the Binary Ni-Ga System
Authors: Chang Chih-Chia Bill , Kao C. R.
Published: February 2024

The assembly of Ga alloys with Ni or Ni alloy has been widely developed for various low-temperature applications in recent years. In the constituent Ni-Ga binary system, however, the phase equilibrium with the phase “NiGa5” and its stability has scarcely been investigated. The present study used the diffusion couple technique combined with SEM-EPMA and XRD analysis to examine the phase stability and the homogeneity range of the phase. The results show that “NiGa5” is a stable phase in the binary system with little homogeneity range and suggest that the peritectic reaction L+Ni3Ga7→NiGa5 lies between 112.0 and 115.5 °C. This work provides new information for the modification of the Ga-rich low-T region of the Ni-Ga phase diagram.