bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Neutrophil Extracellular Traps in Health and Disease Pathophysiology: Recent Insights and Advances
Authors: Islam Md. Monirul , Takeyama Naoshi
Published: October 2023

Neutrophils are the principal trouper of the innate immune system. Activated neutrophils undergo a noble cell death termed NETosis and release a mesh-like structure called neutrophil extracellular traps (NETs) as a part of their defensive strategy against microbial pathogen attack. This web-like architecture includes a DNA backbone embedded with antimicrobial proteins like myeloperoxidase (MPO), neutrophil elastase (NE), histones and deploys in the entrapment and clearance of encountered pathogens. Thus NETs play an inevitable beneficial role in the host’s protection. However, recent accumulated evidence shows that dysregulated and enhanced NET formation has various pathological aspects including the promotion of sepsis, pulmonary, cardiovascular, hepatic, nephrological, thrombotic, autoimmune, pregnancy, and cancer diseases, and the list is increasing gradually. In this review, we summarize the NET-mediated pathophysiology of different diseases and focus on some updated potential therapeutic approaches against NETs.
Why Do We Study Aquatic Organisms?
Authors: Kloc Malgorzata , Kubiak Jacek Z.
Published: October 2023

Aquatic organisms comprising various plant and animal taxa represent a wide range of adaptations to a specific environment, but they also share many features with nonaquatic organisms of a given taxonomic group.[...]
Genetic and Lifestyle-Related Factors Influencing Serum Hyper-Propionylcarnitine Concentrations and Their Association with Metabolic Syndrome and Cardiovascular Disease Risk
Authors: Lee Yong-Hwa , Park Sunmin
Published: October 2023

The genetic and environmental determinants of serum propionylcarnitine concentrations (PC) remain largely unexplored. This study investigated the impact of genetic and environmental factors on serum propionylcarnitine levels in middle-aged and elderly participants from the Ansan/Ansung cohort of the Korean Genome and Epidemiology Study. Our goal was to understand the role of PC on the risk of metabolic syndrome (MetS) leading to cardiovascular disease, particularly concerning branched-chain amino acid (BCAA) metabolism. We analyzed participants’ demographic, lifestyle, and biochemical data with and without MetS. Serum metabolite concentrations, including carnitine, acylcarnitine, and amino acid concentrations, were measured, and the components of MetS were evaluated. Genetic variants associated with low and high PC were selected using genome-wide association studies after adjusting for MetS-related parameters. Further, genetic variants and lifestyle factors that interacted with the polygenic risk score (PRS) were analyzed. Participants with MetS were older and less educated, and their alcohol intake was higher than non-MetS participants. PC was significantly associated with the MetS risk and increased the serum levels of BCAAs and other amino acids. Higher PC positively correlated with MetS components, insulin resistance, and cardiovascular risk factors. Intake of calcium, sodium, and vitamin D were inversely associated with PC, but coffee consumption was positively linked to PC. Multiple C2 And Transmembrane Domain Containing-1 (MCTP1)_rs4290997, Kinesin Family Member-7 (KIF7)_rs2350480, Coagulation Factor-II (F2)_rs2070850, Peroxisomal Biogenesis Factor-3 (PEX3)_rs223231, TBC1 Domain Family Member-22A (TBC1D22A)_rs910543, and Phospholipase A2 Group-IV-C (PLA2G4C)_rs7252136 interact with each other to have a threefold influence on PC. The PRS for the six-genetic variant model also interacted with age; the diet rich in beans, potato, and kimchi; and smoking status, influencing PC. In conclusion, elevated PC was associated with MetS and cardiovascular disease risk, suggesting their potential as disease biomarkers.
Chemical Chaperone 4-PBA Mitigates Tumor Necrosis Factor Alpha-Induced Endoplasmic Reticulum Stress in Human Airway Smooth Muscle
Authors: Delmotte Philippe , Yap Jane Q. , Dasgupta Debanjali , Sieck Gary C.
Published: October 2023

Airway inflammation and pro-inflammatory cytokines such as tumor necrosis factor alpha (TNFα) underlie the pathophysiology of respiratory diseases, including asthma. Previously, we showed that TNFα activates the inositol-requiring enzyme 1α (IRE1α)/X-box binding protein 1 spliced (XBP1s) endoplasmic reticulum (ER) stress pathway in human airway smooth muscle (hASM) cells. The ER stress pathway is activated by the accumulation of unfolded proteins in the ER. Accordingly, chemical chaperones such as 4-phenylbutyric acid (4-PBA) may reduce ER stress activation. In the present study, we hypothesized that chemical chaperone 4-PBA mitigates TNFα-induced ER stress in hASM cells. hASM cells were isolated from bronchiolar tissue obtained from five patients with no history of smoking or respiratory diseases. The hASM cells’ phenotype was confirmed via the expression of alpha-smooth muscle actin and elongated morphology. hASM cells from the same patient sample were then separated into three 12 h treatment groups: (1) TNFα (20 ng/mL), (2) TNFα + 4-PBA (1 μM, 30 min pretreatment), and (3) untreated control. The expressions of total IRE1α and phosphorylated IRE1α (pIRE1αS724) were determined through Western blotting. The splicing of XBP1 mRNA was analyzed using RT-PCR. We found that TNFα induced an increase in pIRE1αS724 phosphorylation, which was mitigated by treatment with chemical chaperone 4-PBA. We also found that TNFα induced an increase in XBP1s mRNA, which was also mitigated by treatment with chemical chaperone 4-PBA. These results support our hypothesis and indicate that chemical chaperone 4-PBA treatment mitigates TNFα-induced ER stress in hASM cells.
Structural Variation Evolution at the 15q11-q13 Disease-Associated Locus
Authors: Paparella Annalisa , L’Abbate Alberto , Palmisano Donato , Chirico Gerardina , Porubsky David , Catacchio Claudia R. , Ventura Mario , Eichler Evan E. , Maggiolini Flavia A. M. , Antonacci Francesca
Published: October 2023

The impact of segmental duplications on human evolution and disease is only just starting to unfold, thanks to advancements in sequencing technologies that allow for their discovery and precise genotyping. The 15q11-q13 locus is a hotspot of recurrent copy number variation associated with Prader–Willi/Angelman syndromes, developmental delay, autism, and epilepsy and is mediated by complex segmental duplications, many of which arose recently during evolution. To gain insight into the instability of this region, we characterized its architecture in human and nonhuman primates, reconstructing the evolutionary history of five different inversions that rearranged the region in different species primarily by accumulation of segmental duplications. Comparative analysis of human and nonhuman primate duplication structures suggests a human-specific gain of directly oriented duplications in the regions flanking the GOLGA cores and HERC segmental duplications, representing potential genomic drivers for the human-specific expansions. The increasing complexity of segmental duplication organization over the course of evolution underlies its association with human susceptibility to recurrent disease-associated rearrangements.
Animal Models of Human Disease
Authors: Lange Sigrun , Inal Jameel M.
Published: October 2023

The use of animal models of human disease is critical for furthering our understanding of disease mechanisms, for the discovery of novel targets for treatment, and for translational research. This Special Topic entitled “Animal Models of Human Disease” aimed to collect state-of-the-art primary research studies and review articles from international experts and leading groups using animal models to study human diseases. Submissions were welcomed on a wide range of animal models and pathologies, including infectious disease, acute injury, regeneration, cancer, autoimmunity, degenerative and chronic disease. Seven participating MDPI journals supported the Special Topic, namely: Biomedicines, Cells, Current Issues in Molecular Biology, Diagnostics, Genes, the International Journal of Molecular Sciences, and the International Journal of Translational Medicine. In total, 46 papers were published in this Special Topic, with 37 full length original research papers, 2 research communications and 7 reviews. These contributions cover a wide range of clinically relevant, translatable, and comparative animal models, as well as furthering understanding of fundamental sciences, covering topics on physiological processes, on degenerative, inflammatory, infectious, autoimmune, neurological, metabolic, heamatological, hormonal and mitochondrial disorders, developmental processes and diseases, cardiology, cancer, trauma, stress, and ageing.
Adverse Effects of Micro- and Nanoplastics on Humans and the Environment
Authors: Niccolai Elena , Colzi Ilaria , Amedei Amedeo
Published: October 2023

The pervasive pollution caused by nano- and microplastics (N/MPLs) is a pressing concern, and was exacerbated during the COVID-19 pandemic due to the substantial release of disposable Personal Protective Equipment (PPE) into the environment [...]
Unveiling the Molecular Landscape of FOXA1 Mutant Prostate Cancer: Insights and Prospects for Targeted Therapeutic Strategies
Authors: Hwang Kyung Won , Yun Jae Won , Kim Hong Sook
Published: October 2023

Prostate cancer continues to pose a global health challenge as one of the most prevalent malignancies. Mutations of the Forkhead box A1 (FOXA1) gene have been linked to unique oncogenic features in prostate cancer. In this study, we aimed to unravel the intricate molecular characteristics of FOXA1 mutant prostate cancer through comprehensive in silico analysis of transcriptomic data from The Cancer Genome Atlas (TCGA). A comparison between FOXA1 mutant and control groups unearthed 1525 differentially expressed genes (DEGs), which map to eight intrinsic and six extrinsic signaling pathways. Interestingly, the majority of intrinsic pathways, but not extrinsic pathways, were validated using RNA-seq data of 22Rv1 cells from the GEO123619 dataset, suggesting complex biology in the tumor microenvironment. As a result of our in silico research, we identified novel therapeutic targets and potential drug candidates for FOXA1 mutant prostate cancer. KDM1A, MAOA, PDGFB, and HSP90AB1 emerged as druggable candidate targets, as we found that they have approved drugs throughout the drug database CADDIE. Notably, as most of the approved drugs targeting MAOA and KDM1A were monoamine inhibitors used for mental illness or diabetes, we suggest they have a potential to cure FOXA1 mutant primary prostate cancer without lethal side effects.
Involvement of the Calmodulin-like Protein Gene VaCML92 in Grapevine Abiotic Stress Response and Stilbene Production
Authors: Aleynova Olga A. , Kiselev Konstantin V. , Suprun Andrey R. , Ananev Alexey A. , Dubrovina Alexandra S.
Published: October 2023

Calmodulin-like proteins (CMLs) are an important family of plant calcium sensor proteins that sense and decode changes in the intracellular calcium concentration in response to environmental and developmental stimuli. Nonetheless, the specific functions of individual CML family members remain largely unknown. This study aims to explore the role of the Vitis amurensis VaCML92 gene in the development of its high stress resistance and the production of stilbenes. The expression of VaCML92 was sharply induced in V. amurensis cuttings after cold stress. The VaCML92 gene was cloned and its role in the abiotic stress responses and stilbene production in grapevine was further investigated. The VaCML92-overexpressing callus cell cultures of V. amurensis and soil-grown plants of Arabidopsis thaliana exhibited enhanced tolerance to cold stress and, to a lesser extent, to the drought, while their tolerance to heat stress and high salinity was not affected. In addition, the overexpression of VaCML92 increased stilbene production in the V. amurensis cell cultures by 7.8–8.7-fold. Taken together, the data indicate that the VaCML92 gene is involved as a strong positive regulator in the rapid response to cold stress, the induction of cold stress resistance and in stilbene production in wild grapevine.
Far-Infrared Ameliorates Pb-Induced Renal Toxicity via Voltage-Gated Calcium Channel-Mediated Calcium Influx
Authors: Ko Chin-Meng , Then Chee-Kin , Kuo Yu-Ming , Lin Yen-Kuang , Shen Shing-Chuan
Published: October 2023

Far-infrared (FIR), characterized by its specific electromagnetic wavelengths, has emerged as an adjunctive therapeutic strategy for various diseases, particularly in ameliorating manifestations associated with renal disorders. Although FIR was confirmed to possess antioxidative and anti-inflammatory attributes, the intricate cellular mechanisms through which FIR mitigates lead (Pb)-induced nephrotoxicity remain enigmatic. In this study, we investigated the effects of FIR on Pb-induced renal damage using in vitro and in vivo approaches. NRK52E rat renal cells exposed to Pb were subsequently treated with ceramic-generated FIR within the 9~14 μm range. Inductively coupled plasma mass spectrometry (ICP-MS) enabled quantitative Pb concentration assessment, while proteomic profiling unraveled intricate cellular responses. In vivo investigations used Wistar rats chronically exposed to lead acetate (PbAc) at 6 g/L in their drinking water for 15 weeks, with or without a concurrent FIR intervention. Our findings showed that FIR upregulated the voltage-gated calcium channel, voltage-dependent L type, alpha 1D subunit (CaV1.3), and myristoylated alanine-rich C kinase substrate (MARCKS) (p < 0.05), resulting in increased calcium influx (p < 0.01), the promotion of mitochondrial activity, and heightened ATP production. Furthermore, the FIR intervention effectively suppressed ROS production, concurrently mitigating Pb-induced cellular death. Notably, rats subjected to FIR exhibited significantly reduced blood Pb levels (30 vs. 71 μg/mL; p < 0.01), attenuated Pb-induced glomerulosclerosis, and enhanced Pb excretion compared to the controls. Our findings suggest that FIR has the capacity to counteract Pb-induced nephrotoxicity by modulating calcium influx and optimizing mitochondrial function. Overall, our data support FIR as a novel therapeutic avenue for Pb toxicity in the kidneys.
Auxin Involvement in Ceratopteris Gametophyte Meristem Regeneration
Authors: Withers Kelley A. , Kvamme Athena , Youngstrom Christopher E. , Yarvis Rebekah M. , Orpano Rachel , Simons Gabriel P. , Irish Erin E. , Cheng Chi-Lien
Published: October 2023

Growth and development of the Ceratopteris hermaphroditic gametophytes are dependent on cell proliferation in the marginal meristem, which when destroyed will regenerate at a new location on the body margin. We established a laser ablation method to destroy a single initial cell in the meristem. Ablation caused the cessation of cell proliferation accompanied by the disappearance of the expression of an auxin synthesis gene (CrTAA2) and a cell proliferation marker gene (CrWOXB). New meristem regeneration occurred within a predictable distance from the original two days post-ablation, signified by cell proliferation and the expression of CrTAA2. Treatment with the naturally occurring auxin indole-3-acetic acid (IAA), synthetic auxin 2,4-dichlorophenoxyacetic acid (2,4-D), or the transport inhibitor naphthylphthalamic acid (NPA) altered positioning of the original marginal meristem toward the apex of the gametophyte. IAA altered positioning of the regenerated meristem after damaging the original meristem. A model of auxin involvement in the positioning of the marginal meristem in Ceratopteris is presented to encompass these results.
Phylosymbiosis: The Eco-Evolutionary Pattern of Insect–Symbiont Interactions
Authors: Qin Man , Jiang Liyun , Qiao Gexia , Chen Jing
Published: October 2023

Insects harbor diverse assemblages of bacterial and fungal symbionts, which play crucial roles in host life history. Insects and their various symbionts represent a good model for studying host–microbe interactions. Phylosymbiosis is used to describe an eco-evolutionary pattern, providing a new cross-system trend in the research of host-associated microbiota. The phylosymbiosis pattern is characterized by a significant positive correlation between the host phylogeny and microbial community dissimilarities. Although host–symbiont interactions have been demonstrated in many insect groups, our knowledge of the prevalence and mechanisms of phylosymbiosis in insects is still limited. Here, we provide an order-by-order summary of the phylosymbiosis patterns in insects, including Blattodea, Coleoptera, Diptera, Hemiptera, Hymenoptera, and Lepidoptera. Then, we highlight the potential contributions of stochastic effects, evolutionary processes, and ecological filtering in shaping phylosymbiotic microbiota. Phylosymbiosis in insects can arise from a combination of stochastic and deterministic mechanisms, such as the dispersal limitations of microbes, codiversification between symbionts and hosts, and the filtering of phylogenetically conserved host traits (incl., host immune system, diet, and physiological characteristics).
Glomerular Hyperfiltration: A Marker of Fibrosis Severity in Metabolic Associated Steatotic Liver Disease in an Adult Population
Authors: Dalbeni Andrea , Garbin Marta , Zoncapè Mirko , Romeo Sara , Cattazzo Filippo , Mantovani Anna , Cespiati Annalisa , Fracanzani Anna Ludovica , Tsochatzis Emmanouil , Sacerdoti David , Mantovani Alessandro , Lombardi Rosa
Published: October 2023

Glomerular hyperfiltration (GH) is an increase in the glomerular filtration rate, possibly progressing to chronic kidney disease (CKD). Metabolic-associated steatotic liver disease (MASLD) is linked to an increased risk of CKD, especially if fibrosis is present; however, the association between GH and MASLD has not been explored. To evaluate GH prevalence in MASLD and its possible correlation with liver fibrosis. 772 consecutive patients with ultrasound MASLD (mean age 47.3 ± 8.9 years, 67.1% males) were enrolled. GH was defined as estimated glomerular filtration rate (eGFR) greater than the upper quartile of values in the cohort. Liver stiffness measurement (LSM) by FibroScan ≥ 7.2 kPa suggested liver fibrosis. GH was present in 20% of patients, liver fibrosis in 30%. In total, 53.4% of the cohort was obese, 40.9% hypertensive, 36.3% diabetic and 70.8% dyslipidaemic. GH patients compared to non-GH were significantly younger (38.4 ± 8.3 vs. 49.5 ± 7.7, p < 0.001), with higher prevalence of LSM > 7.2 kPa (35.5% vs. 29%, p < 0.001), without any difference in metabolic comorbidities. In multivariate analysis, age (OR 0.85, CI 95% 0.82–0.87) and significant fibrosis (OR 1.83; CI 95%1.10–3.03) remained independently associated with GH, regardless of the presence of metabolic alterations and nephrotoxic drugs. GH, an early marker of renal damage, is highly prevalent in MASLD and is associated with hepatic fibrosis. GH may be considered an early marker of both liver and renal disease and its recognition could prompt the management of risk factors aimed at preventing the progression of both hepatic and renal disease.
Age-Related Shift in Cardiac and Metabolic Phenotyping Linked to Inflammatory Cytokines and Antioxidant Status in Mice
Authors: Kang Ryeonshi , Laborde Charlotte , Savchenko Lesia , Swiader Audrey , Pizzinat Nathalie , Marsal Dimitri , Sainte-Marie Yannis , Boal Frederic , Tronchere Helene , Roncalli Jerome , Kunduzova Oksana
Published: October 2023

Age-related alterations in cardiac function, metabolic, inflammatory and antioxidant profiles are associated with an increased risk of cardiovascular mortality and morbidity. Here, we examined cardiac and metabolic phenotypes in relation to inflammatory status and antioxidant capacity in young, middle-aged and old mice. Real-time reverse transcription–polymerase chain reactions were performed on myocardium and immunoassays on plasma. Left ventricular (LV) structure and function were assessed by echocardiography using high-frequency ultrasound. Middle-aged mice exhibited an altered metabolic profile and antioxidant capacity compared to young mice, whereas myocardial expression of inflammatory factors (TNFα, IL1β, IL6 and IL10) remained unchanged. In contrast, old mice exhibited increased expression of inflammatory cytokines and plasma levels of resistin compared to young and middle-aged mice (p < 0.05). The pro-inflammatory signature of aged hearts was associated with alterations in glutathione redox homeostasis and elevated contents of 4-hydroxynonenal (4-HNE), a marker of lipid peroxidation and oxidative stress. Furthermore, echocardiographic parameters of LV systolic and diastolic functions were significantly altered in old mice compared to young mice. Taken together, these findings suggest age-related shifts in cardiac phenotype encompass the spectrum of metabo-inflammatory abnormalities and altered redox homeostasis.
Rifaximin Reduces Risk of All-Cause Hospitalization in Cirrhotic Liver Transplant Candidates with Hepatic Encephalopathy
Authors: Parisse Simona , Lai Quirino , Martini Francesca , Martini Alice , Ferri Flaminia , Mischitelli Monica , Melandro Fabio , Mennini Gianluca , Rossi Massimo , Alvaro Domenico , Ginanni Corradini Stefano
Published: October 2023

In cirrhotic patients listed for liver transplantation (LT) with a history of hepatic encephalopathy (HE), rifaximin reduces the number of hospitalizations, but whether it influences the time to first hospitalization is unknown. Aims: to evaluate the time-dependent impact of rifaximin on the risk of all-cause hospitalization and dropout in patients on the LT waiting list. Methods: Consecutive patients listed for LT were retrospectively enrolled. After balancing populations with and without rifaximin treatment using the inverse probability therapy weighting analysis, Fine–Gray multivariable competing risk analyses were run to explore risk factors for the first episode of hospitalization and dropout. Results: When comparing 92 patients taking rifaximin to the untreated group of 152, rifaximin treatment was not associated with any of the study outcomes. In the subset of patients with a history of HE at waitlist entry (N = 81 rifaximin-treated and N = 39 untreated), rifaximin intake was independently associated with a lower risk of hospitalization for all causes (SHR 0.638; 95.0% CI 0.418–0.973; p = 0.037) and for HE (SHR 0.379; 95.0% CI 0.207–0.693; p = 0.002). Conclusions: cirrhotic LT candidates with a prior history of HE rifaximin treatment are associated with a lower risk of time-dependent all-cause hospitalization, likely due to its unique effect on gut microbiome composition/function.
Influence of Diabetes Mellitus and Nutritional Parameters on Clinical and Functional Aspects and Quality of Life in Patients Hospitalized Due to Exacerbation of Chronic Obstructive Pulmonary Disease
Authors: Correa-Gutiérrez Cristhian Alonso , Ji Zichen , Aragón-Espinosa Patricia , Rodrigues-Oliveira Sarah , Zeng Luyi , Meizoso-Pita Olalla , Sevillano-Collantes Cristina , Hernández-Vázquez Julio , Puente-Maestu Luis , de Miguel-Díez Javier
Published: October 2023

Patients with chronic obstructive pulmonary disease (COPD) may experience exacerbations. During severe exacerbations, nutritional and endocrinological comorbidities can play an important role in the clinical and functional aspects of these patients. The aim of this study was to analyse the influence of the presence of diabetes mellitus (DM) and nutritional parameters on the deterioration of symptoms and quality of life during a severe exacerbation in patients with COPD. An observational study was conducted on COPD patients admitted due to an exacerbation. The COPD Assessment Test (CAT) questionnaire was administered, and clinical and functional parameters were compared based on the presence of nutritional and endocrinological alterations. A total of 50 patients were included, of whom 30 (60%) were male. The mean age was 70.5 years (standard deviation (SD) 9.6). The median CAT score during exacerbation was 25 (interquartile range (IQR) 17.5–30), and the baseline score was 13.5 (IQR 7–19), which represented a statistically significant difference (p < 0.001). Patients with iron deficiencies had a lower total CAT score (p = 0.041), specifically for items related to daily activity (p = 0.009) and energy (p = 0.007). Diabetic patients exhibited a greater decline in pulmonary function during exacerbation (p = 0.016), while patients with high thyroid-stimulating hormone (TSH) levels had a shorter hospital stay (p = 0.016). For COPD patients admitted due to an exacerbation, the metabolic assessment is useful and relevant in the clinical set-up, as endocrinological comorbidities negatively affect clinical and functional aspects of these patients.
Over a Century of Study and Still Misunderstood: Recognizing the Spectrum of Acute and Chronic Wernicke–Korsakoff Syndrome
Authors: Scalzo Simon J. , Bowden Stephen C.
Published: October 2023

The aim of this study was to objectively evaluate the hypothesis that the neuropsychological presentation of Korsakoff’s syndrome, the chronic phase of Wernicke–Korsakoff syndrome (WKS), is invariably a severe, selective amnesia against a background of relatively preserved general intellectual functions in a consecutive clinical sample. An analysis of the neuropsychological profiles of nine cases with a recorded history of WKS was undertaken. All cases were adult males (ages 32 to 70) with a long history of alcohol use disorder. Eight cases were chosen retrospectively on a consecutive basis from patient referrals. One additional case was recruited prospectively. Conventional understanding and some current opinion of Korsakoff’s syndrome predicts anterograde memory to be consistently more impaired than other cognitive abilities, but this was not found in this case series. The Mean Wechsler Delayed Memory Index was not significantly different from the Wechsler Full-Scale IQ (FSIQ), p = 0.130. Regression of Delayed Memory on FSIQ produced a non-significant intercept, p = 0.213. The ‘hallmark’ criterion of anterograde memory score at least 20 points less than intelligence score was observed in four of eight cases with available data, equating to a ‘sensitivity’ of 50%. Three of eight cases with available data had an FSIQ less than the memory score. Contrary to a common view, general intellectual function was not consistently preserved in Korsakoff’s syndrome relative to memory function. This study illustrates one of the specific merits of case series, namely, to critique an established view. Clinicians and researchers should expand their diagnostic criteria for Korsakoff’s syndrome to include more variable cognitive phenotypes, including a potentially reversible dementia-like impairment of variable severity, and focus on potential treatment opportunities.
Fear of COVID-19 Predicts Depression, Anxiety and Post-Traumatic Stress Disorders in Patients with Implantable Cardioverter Defibrillators and Is Mediated by Positive and Negative Affects—A Cross-Sectional Study
Authors: Dörner Marc , von Känel Roland , Pazhenkottil Aju P. , Altwegg Rahel , Nager Ladina , Attanasio Veronica , Guth Lisa , Zirngast Sina , Menzi Anna , Princip Mary , Hackl-Zuccarella Claudia
Published: October 2023

The COVID-19 pandemic affected both the physical and mental health of the general population. People with cardiac diseases seem to be particularly vulnerable to the implications of the pandemic. However, studies on the mental health impact of the COVID-19 pandemic on people with implantable cardioverter defibrillator (ICDs) are lacking. Thus, we aimed to explore the level of fear of COVID-19 and the prevalence of anxiety, depression and post-traumatic stress disorder (PTSD) in ICD patients. Furthermore, we aimed to identify novel predictors for anxiety, depression and PTSD, including COVID-19-related variables, and to assess whether positive affects (PAs) and negative affects (NAs) mediate the relationship between the level of fear of COVID-19 and anxiety, depression and PTSD, respectively. The data of 363 patients with ICDS who had been prospectively included in this study between 2020 and 2023, were analyzed. Potential predictors for anxiety, depression, and PTSD were identified using logistic regression. To identify indirect mediating effects of PAs and NAs, we applied the PROCESS regression path analysis modeling tool. The prevalence of anxiety was 9.19%, of depression 10.85%, and of PTSD 12.99%. Being unemployed was the strongest predictor for anxiety (OR = 10.39) and depression (OR = 6.54). Younger age predicted anxiety (OR = 0.95) and PTSD (OR = 0.92). Receiving low social support was associated with anxiety (OR = 0.91), depression (OR = 0.88) and PTSD (OR = 0.91). Patients with a history of COVID-19 (OR = 3.58) and those who did not feel well-informed about COVID-19 (OR = 0.29) were more likely to be depressed. Higher levels of fear of COVID-19 predicted anxiety (OR = 1.10), depression (OR = 1.12) and PTSD (OR = 1.14). The relationship between fear of COVID-19 and anxiety or depression was fully mediated by PAs and NAs, while NAs partially mediated the relationship between fear of COVID-19 and PTSD. Vulnerable subgroups of ICD patients may need additional psychological and educational interventions due to fear of COVID-19, anxiety, depression and PTSD during the pandemic.
Grounding the Restorative Effect of the Environment in Tertiary Qualities: An Integration of Embodied and Phenomenological Perspectives
Authors: Biassoni Federica , Gandola Michela , Gnerre Martina
Published: October 2023

This paper proposes an integration of embodied and phenomenological perspectives to understand the restorative capacity of natural environments. It emphasizes the role of embodied simulation mechanisms in evoking positive affects and cognitive functioning. Perceptual symbols play a crucial role in generating the restorative potential in environments, highlighting the significance of the encounter between the embodied individual and the environment. This study reviews Stress Reduction Theory (SRT) and Attention Restoration Theory (ART), finding commonalities in perceptual fluency and connectedness to nature. It also explores a potential model based on physiognomic perception, where the environment’s pervasive qualities elicit an affective response. Restorativeness arises from a direct encounter between the environment’s phenomenal structure and the embodied perceptual processes of individuals. Overall, this integrative approach sheds light on the intrinsic affective value of environmental elements and their influence on human well-being.
Improving the Accuracy of Satellite-Derived Bathymetry Using Multi-Layer Perceptron and Random Forest Regression Methods: A Case Study of Tavşan Island
Authors: Çelik Osman İsa , Büyüksalih Gürcan , Gazioğlu Cem
Published: October 2023

The spatial and spectral information brought by the Very High Resolution (VHR) and multispectral satellite images present an advantage for Satellite-Derived Bathymetry (SDB), especially in shallow-water environments with dense wave patterns. This work focuses on Tavşan Island, located in the Sea of Marmara (SoM), and aims to evaluate the accuracy and reliability of two machine learning (ML) regression methods, Multi-Layer Perceptron (MLP) and Random Forest (RF), for bathymetry mapping using Worldview-2 (WV-2) imagery. In situ bathymetry measurements were collected to enhance model training and validation. Pre-processing techniques, including water pixel extraction, sun-glint correction, and median filtering, were applied for image enhancement. The MLP and RF regression models were then trained using a comprehensive dataset that included spectral bands from the satellite image and corresponding ground truth depth values. The accuracy of the models was assessed using metrics such as Root-Mean-Square Error (RMSE), Mean Absolute Error (MAE), and R2 value. The RF regression model outperformed the MLP model, with a maximum R2 value of 0.85, lowest MAE values from 0.65 to 1.86 m, and RMSE values from 0.93 to 2.41 m at depth intervals between 6 and 9 m. These findings highlight the effectiveness of ML regression methods, specifically the RF model, for SDB based on remotely sensed images in wave-dense shallow-water environments.
Vibrational Responses of an Ultra-Large Cold-Water Pipe for Ocean Thermal Energy Conversion: A Numerical Approach
Authors: Tan Jian , Zhang Yulong , Zhang Li , Duan Qingfeng , An Chen , Duan Menglan
Published: October 2023

The transportation of seawater on a grand scale via an ultra-large cold-water pipe situated within the context of ocean thermal energy conversion (OTEC) floating installations inherently presents challenges associated with instability and potential malfunction in the face of demanding operational circumstances. This study endeavors to augment the stability and security of cold-water pipe (CWP) operations by scrutinizing their vibrational attributes across diverse boundary configurations. Initially, we invoke Euler–Bernoulli beam theory to forge the analytical framework and proffer a semi-analytical resolution by utilizing the generalized integral transform technique (GITT). Subsequently, we authenticate the convergence and precision of our proposed approach through comparative analysis with extant theories. Our findings underscore the conspicuous influence of boundary conditions on the convergence of transverse displacement. The influence of internal flow on the transverse displacement and the natural frequency manifests substantial variability under different boundary conditions. Significantly, an escalation in the internal flow velocity triggers a concomitant reduction in the natural frequency, ultimately culminating in instability once the critical velocity threshold is reached. Additionally, the reliance of the transverse displacement and the natural frequency on the clump weight at the bottom is markedly pronounced. Our discoveries propose that pipe stability can be ameliorated by adjusting the clump weight at the bottom. Furthermore, the novel insights obtained through our proposed approach can significantly aid in the early-stage design and analysis of CWP.
Compatibility Assessment of Novel Orodispersible Film Vehicle for Personalized Medicine with Selected Active Pharmaceutical Ingredients
Authors: Polonini Hudson C. , Ferreira Anderson O. , Raposo Nádia R. B. , da Silva Paulo José L. C. , Brandão Marcos Antônio F.
Published: October 2023

Orodispersible films (ODFs) are solid pharmaceutical forms for rapid local or systemic release of active ingredients. They are formed by a water-soluble polymer film that hydrates rapidly, adhering and dissolving immediately when placed on the tongue or in the oral cavity. In this paper, we describe the compatibility and disintegration times of compounded ODFs using OrPhylloTM, a new ready-to-use-vehicle, and APIs from different pharmacological classes, such as 5-hydroxytryptophan (5-HTP) 50 mg, bromopride 5 mg, coenzyme Q10 20 mg, melatonin 3 mg, resveratrol 5 mg, tadalafil 10 mg, vitamin B12 1 mg, or vitamin D3 2000 UI. ODFs were compounded and, subsequently, the samples were assayed using HPLC at initial (t = 0), 7 days (t = 7), 14 days (t = 14), 30 days (t = 30), 60 days (t = 60), 90 days (t = 90), 120 days (t = 120), 150 days (t = 150), and 180 days (t = 180) after compounding. Given the percentage of recovery of the APIs within the films, the beyond-use date of the final products (API + vehicle) was at least 90 days for vitamin D3, 150 days for bromopride and 5-HTP, and 180 days for coenzyme Q10, tadalafil, vitamin B12, resveratrol, and melatonin, when stored at room temperature. The average disintegration time was 46.22 s. This suggests that the OrPhylloTM vehicle is suitable for compounding ODFs with APIs from different pharmacological classes, with good compatibility and fast disintegration.
Monitoring Seasonal Fluctuations in Saline Lakes of Tunisia Using Earth Observation Data Processed by GRASS GIS
Authors: Lemenkova Polina
Published: October 2023

This study documents the changes in the Land Use/Land Cover (LULC) in the region of saline lakes in north Tunisia, Sahara Desert. Remote sensing data are a valuable data source in monitoring LULC in lacustrine landscapes, because variations in the extent of lakes are visible from space and can be detected on the images. In this study, changes in LULC of the salt pans of Tunisia were evaluated using a series of 12 Landsat 8-9 Operational Land Imager (OLI) and Thermal Infrared (TIRS) images. The images were processed with the Geographic Resources Analysis Support System (GRASS) Geographic Information System (GIS) software. The study area included four salt lakes of north Tunisia in the two regions of the Gulf of Hammamet and Gulf of Gabès: (1) Sebkhet de Sidi el Hani (Sousse Governorate), (2) Sebkha de Moknine (Mahdia Governorate), (3) Sebkhet El Rharra and (4) Sebkhet en Noual (Sfax). A quantitative estimate of the areal extent analysed in this study is 182 km × 185 km for each Landsat scene in two study areas: Gulf of Hammamet and Gulf of Gabès. The images were analysed for the period 2017–2023 on months February, April and July for each year. Spatio-temporal changes in LULC and their climate–environmental driving forces were analysed. The results were interpreted and the highest changes were detected by accuracy assessment, computing the class separability matrices, evaluating the means and standard deviation for each band and plotting the reject probability maps. Multi-temporal changes in LULC classes are reported for each image. The results demonstrated that changes in salt lakes were determined for winter/spring/summer months as detected changes in water/land/salt/sand/vegetation areas. The accuracy of the classified images was evaluated using pixel rejection probability values, which were filtered out using the ‘r.mapcalc’ module of GRASS GIS. The confidence levels were computed and visualised with a series of maps along with the error matrix and measured convergence level of classified pixels. This paper contributes to the environmental monitoring of Tunisian landscapes and analysis of climate effects on LULC in landscapes of north Africa.
Transition Characteristics and Driving Mechanisms of Rural Settlements in Suburban Villages of Megacities under Policy Intervention: A Case Study of Dayu Village in Shanghai, China
Authors: Li Kaiming , Li Kaishun , Liu Yong , Yue Liying , Jiang Xiji
Published: October 2023

China’s distinct rural revitalization process has attracted global attention due to its impressive speed, massive scale, and policy interventions. A relatively limited amount of research has been conducted on how rural transition characteristics and policy mechanisms are interrelated at the micro level. To fill this research gap, following the main research thread of dividing rural development stages, revealing transition characteristics and exploring policy mechanisms, this paper utilizes a participatory rural appraisal, a landscape metrics analysis, and in-depth interviews to analyze the spatial transition laws of Dayu Village. First, the results show that the village experienced three stages from 1990 to 2020: strict homestead control, village relocation, and land consolidation. Second, the village exhibits multidimensional transition characteristics. With a reduced rural settlement area, regular patch formation, and a dense interior subdivision of rural houses, the land use layout changed from homogeneous to multiple nests. As the industrial structure became more diversified, the villagers’ livelihoods became more differentiated. Inflows of tourists and migrants changed the population structure, causing social relations to become defamiliarized. Moreover, mechanism research finds that policy can promote rural settlement transition by allocating land resources and regulating village behavior. The policy’s scope expanded from a single settlement to the whole village, optimizing external forces, with village behavior effects acting as an internal force. The degree of matching between policy formulation and villagers’ needs is the key to promoting the transition of rural settlements. This research deepens the understanding of the transition laws of suburban villages in megacities in developing countries at the micro scale and provides a reference for land policies in similar villages.
Enhanced Microvascular Adaptation to Acute Physical Stress and Reduced Oxidative Stress in Male Athletes Who Consumed Chicken Eggs Enriched with n-3 Polyunsaturated Fatty Acids and Antioxidants—Randomized Clinical Trial
Authors: Kolar Luka , Šušnjara Petar , Stupin Marko , Stupin Ana , Jukić Ivana , Mihaljević Zrinka , Kolobarić Nikolina , Bebek Iva , Nejašmić Diana , Lovrić Marija , Drenjančević Ines
Published: October 2023

This randomized interventional study aimed to determine the effects of n-3 polyunsaturated fatty acids, selenium, vitamin E, and lutein supplementation in the form of enriched chicken egg consumption on microvascular endothelium-dependent vasodilation, oxidative stress, and microvascular response to an acute strenuous training session (ASTS) in competitive athletes. Thirty-one male athletes were assigned to a control (n = 17) or a Nutri4 group (n = 14) who consumed three regular or enriched chicken eggs per day, respectively, for 3 weeks. Significantly enhanced endothelium-dependent responses to vascular occlusion (PORH) and iontophoresis of acetylcholine (AChID) were observed in the Nutri4 group but not in the control group after egg consumption. Formation of peroxynitrite and hydrogen peroxide in peripheral blood mononuclear cells, as well as serum concentration of 8-iso prostaglandin F2α, decreased in the Nutri4 group while remaining unchanged in controls. PORH and AChID were reduced post-ASTS compared with pre-ASTS, both before and after the diets, in both groups. However, the range of PORH responsiveness to ASTS (ΔPORH) increased after consumption of enriched eggs. These results suggest that consumption of enriched chicken eggs has a beneficial effect on microvascular endothelium-dependent vasodilation and the reduction of oxidative stress levels in competitive athletes. Also, microvascular adaptation to the ASTS was improved after consumption of Nutri4 eggs.
Differential Expression of Serum Proinflammatory Cytokine TNF-α and Genetic Determinants of TNF-α, CYP2C19*17, miR-423 Genes and Their Effect on Coronary Artery Disease Predisposition and Progression
Authors: Almassabi Rehab F. , Mir Rashid , Javid Jamsheed , AbuDuhier Faisel M. , Almotairi Reema , Alhelali Marwan H. , Algehainy Naseh , Alsaedi Basim S. O. , Albalawi Salem Owaid , Elfaki Imadeldin
Published: October 2023

Coronary artery disease (CAD) is the leading cause of death and hospitalization worldwide and represents a problem for public health systems everywhere. In Saudi Arabia, the prevalence of CAD is estimated to be 5.5%. Risk factors for CAD include older age, male gender, obesity, high blood pressure, smoking, diabetes, hyperlipidemia, and genetic factors. Reducing the risk factors in susceptible individuals will decrease the prevalence of CAD. Genome wide association studies have helped to reveal the association of many loci with diseases like CAD. In this study, we examined the link between single nucleotide variations (SNVs) of TNF-α-rs1800629 G>A, CYP2C19*17 (rs12248560) C>T, and miR-423 rs6505162 C>A and the expression of TNF-α with CAD. We used the mutation specific PCR, ARMS-PCR, and ELISA. The results showed that the A allele of the TNF-α rs1800629 G>A SNP is linked to CAD with odd ratio (OR) (95% CI) = 2.10, p-value = 0.0013. The T allele of the CYP2C19*17 (rs12248560) C>T is linked to CAD with OR (95% CI) = 2.02, p-value = 0.003. In addition, the A allele of the miR-423 rs6505162 C>A SNV is linked to CAD with OR (95% CI) = 1.49, p-value = 0.036. The ELISA results indicated that the TNF-α serum levels are significantly increased in CAD patients compared to healthy controls. We conclude the TNF-α rs1800629 G>A, CYP2C19*17, and miR-423 rs6505162 C>A are potential genetic loci for CAD in the Saudi population. These findings require further verification in future studies. After being verified, our results might be utilized in genetic testing to identify individuals that are susceptible to CAD and, therefore, for whom reducing modifiable risk factors (e.g., poor diet, diabetes, obesity, and smoking) would result in prevention or delay of CAD.
Frontiers of Collaboration between Primary Care and Specialists in the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease: A Review
Authors: Nagai Koki , Nagai Kazuki , Iwaki Michihiro , Kobayashi Takashi , Nogami Asako , Oka Masanao , Saito Satoru , Yoneda Masato
Published: October 2023

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), is the most common liver disease. It has a rapidly growing patient population owing to the increasing prevalence of obesity and type 2 diabetes. Patients with MASLD are primarily treated by family physicians when fibrosis is absent or mild and by gastroenterologists/hepatologists when fibrosis is more advanced. It is imperative that a system for the appropriate treatment and surveillance of hepatocellular carcinoma be established in order to ensure that highly fibrotic cases are not overlooked among the large number of MASLD patients. Family physicians should check for viral hepatitis, autoimmune hepatitis, alcoholic liver disease, and drug-induced liver disease, and should evaluate fibrosis using NIT; gastroenterologists/hepatologists should perform liver biopsy, ultrasound elastography (260 units in Japan as of October 2023), and MR elastography (35 units in Japan as of October 2023). This review presents the latest findings in MASLD and the role, accuracy, and clinical use of NIT. It also describes the collaboration between Japanese primary care and gastroenterologists/hepatologists in Japan in the treatment of liver diseases, including MASLD.
Study of the Effect of Retarder and Expander on the Strength and Cracking Performance of Rubber Concrete Based on Back Propagation Neural Network
Authors: Sui Chune , Qiao Dan , Wu Yalong , Zhu Han , Lan Haoyu , Yang Wenjun , Guo Qi
Published: October 2023

The advantages of rubber concrete (RC) are good ductility, fatigue resistance, and impact resistance, but few studies have been conducted on the effects of different rubber admixtures on the strength of RC and the cracking performance of rubber mortar. In this study, the compressive and flexural tests of rubber concrete and the crack resistance test of rubber mortar were carried out by changing the rubber content and adding expansion agent and retarder in this test. The test results show that the strength of RC decreases with the increase in rubber admixture. At 15% of rubber admixture, the expansion agent and retarder increase the compressive strength and flexural strength of RC the most; the compressive strength increased to 116% (22.6 MPa) and 109% (21.2 MPa), and the flexural strength increased to 111% (4.02 MPa) and 116%. (4.21 MPa). At the same rubber admixture, the expander improves the cracking time of the rubber mortar by about 3 times, and the retarder improves the cracking time of the rubber mortar by about 1.6 times. The BP neural network (BPNN) was established to simulate and predict the compressive and flexural strengths of RC with different admixtures and the cracking time of rubber mortar. The simulation results show that the predicted 7-day compressive strength of RC fits best with the actual value, with a value of 0.994, and the predicted 28-day flexural strength was closest to the measured value, with an average relative error of 1.7%. It was shown that the calculation results of the artificial intelligence prediction model are more accurate. The simulation results and test results show that the expander and retarder significantly improve the strength of RC as well as the cracking performance of rubber mortar.