bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Liraglutide, Empagliflozin and Their Combination on Left Atrial Strain and Arterial Function
Authors: Katogiannis Konstantinos , Thymis John , Kousathana Foteini , Pavlidis George , Korakas Emmanouil , Kountouri Aikaterini , Balampanis Konstantinos , Prentza Vasiliki , Kostelli Gavriella , Michalopoulou Helen , Tsilivarakis Damianos , Lambadiari Vaia , Ikonomidis Ignatios
Published: February 2024

Background and Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) are cardioprotective drugs. We investigated their effects on left atrial function, a major determinant of cardiac diastolic dysfunction in type 2 diabetes mellitus. We also explored the association of changes in arterial stiffness with those of the LA strain after treatment. Materials and Methods: A total of 200 patients (59.5 ± 9.1 year old, 151 male) with type 2 diabetes mellitus treated with metformin were randomized to insulin (n = 50 served as controls), liraglutide (n = 50), empagliflozin (n = 50) or their combination (liraglutide + empagliflozin) (n = 50). We measured at baseline and 6 months post-treatment: (a) left atrial and global left ventricular longitudinal strain by speckle tracking echocardiography; (b) pulse wave velocity (PWV) and central systolic blood pressure. Results: At baseline, there was a correlation of the LA reservoir strain with PWV (r = −0.209, p = 0.008), central SBP (r = −0.151, p = 0.030), EF (r = 0.214, p = 0.004) and GLS (r = −0.279, p = 0.009). The LA reservoir change 6 months post-treatment was correlated with the PWV change in all groups (r = −0.242, p = 0.028). The LA reservoir change 6 months post-treatment was correlated with the GLS change in all groups (r = −0.322, p = 0.004). Six months after intervention, patients treated with liraglutide, empagliflozin and their combination improved the left atrial reservoir strain (GLP1RA 30.7 ± 9.3 vs. 33.9 ± 9.7%, p = 0.011, SGLT2i 30 ± 8.3 vs. 32.3 ± 7.3%, p = 0.04, GLP1&SGLT2i 29.1 ± 8.7 vs. 31.3 ± 8.2, p = 0.007) compared to those treated with insulin (33 ± 8.3% vs. 32.8 ± 7.4, p = 0.829). Also, patients treated with liraglutide and the combination liraglutide and empagliflozin had improved left atrial conduction strain (p < 0.05). Empagliflozin or the combination liraglutide and empagliflozin showed a greater decrease of PWV and central and brachial systolic blood pressure than insulin or GLP-1RA. (p < 0.05). Conclusions: Impaired aortic elastic properties are associated with a decreased LA strain in type 2 diabetics. Treatment with liraglutide, empagliflozin and their combination for 6 months showed a greater improvement of left atrial function compared to insulin treatment in parallel with the improvement of arterial and myocardial functions.
Molecular Subtypes, microRNAs and Immunotherapy Response in Metastatic Colorectal Cancer
Authors: Gherman Alexandra , Bolundut Dinu , Ecea Radu , Balacescu Loredana , Curcean Sebastian , Dina Constantin , Balacescu Ovidiu , Cainap Calin
Published: February 2024

Currently, only a limited set of molecular traits are utilized to direct treatment for metastatic CRC (mCRC). The molecular classification of CRC depicts tumor heterogeneity based on gene expression patterns and aids in comprehending the biological characteristics of tumor formation, growth and prognosis. Additionally, it assists physicians in tailoring the therapeutic approach. Microsatellite instability (MSI-H)/deficient mismatch repair proteins (MMRd) status has become a ubiquitous biomarker in solid tumors, caused by mutations or methylation of genes and, in turn, the accumulation of mutations and antigens that subsequently induce an immune response. Immune checkpoint inhibitors (ICI) have recently received approval for the treatment of mCRC with MSI-H/MMRd status. However, certain individuals experience either initial or acquired resistance. The tumor-programmed cell death ligand 1 (PD-L1) has been linked to the ability of CRC to evade the immune system and promote its growth. Through comprehensive research conducted via the PUBMED database, the objectives of this paper were to review the molecular characteristics linked to tumor response in metastatic CRC in light of improved patients’ outcomes following ICI therapies as seen in clinical trials and to identify particular microRNAs that can modulate the expression of specific oncoproteins, such as PD-L1, and disrupt the mechanisms that allow the immune system to be evaded.
Analysis of Factors Contributing to Adverse Events and Evaluation of Their Impact on Prognosis in Metastatic Renal Cell Carcinoma Patients—Real-World Experience in a Single-Center Retrospective Study and Narrative Review
Authors: Domański Piotr , Piętak Mateusz , Staneta Szymon , Fortuniak Weronika , Kruczyk Barbara , Kobiernik Adam , Bakuła Piotr , Mydlak Anna , Demkow Tomasz , Sikora-Kupis Bożena , Dumnicka Paulina , Kucharz Jakub
Published: February 2024

Background and Objectives: More than 430,000 new cases of renal cell carcinoma (RCC) were reported in 2020. Clear cell RCC, which occurs in 80% of cases, is often associated with mutations in the VHL gene, leading to dysregulation of hypoxia-induced transcription factors pathways and carcinogenesis. The purpose of this study is to examine the adverse events (AEs) of cabozantinib treatment and the relationship between individual patient factors and the frequency of their occurrence in detail. Materials and Methods: Seventy-one patients with metastatic RCC were treated with second or further lines of cabozantinib at the Department of Genitourinary Oncology, Maria Sklodowska-Curie National Research Institute of Oncology. Comprehensive data, including demographics, clinicopathological factors, and AEs, were collected from January 2017 to June 2021. This study evaluated the impact of various patient-related factors on the rate of adverse events and treatment tolerance using a Cox proportional hazards model. Results: Cabozantinib-induced AEs were significantly associated with body mass index (BMI), body surface area (BSA), IMDC prognostic score, and treatment line. Notably, patients receiving cabozantinib post-tyrosine kinase inhibitors reported fewer AEs. Dose reduction was unrelated to adverse event frequency, but patients requiring dose reduction were characterized with lower body mass and BSA but not BMI. Conclusions: The factors described make it possible to predict the incidence of AEs, which allows for faster detection and easier management, especially in the high-risk group. AEs should be reported in detail in real-world studies, as their occurrence has a significant impact on prognosis.
Modelling the Sorting of Lithium-Ion Battery Components in a Zig-Zag Air Classifier
Authors: Kaas Alexandra , Wilke Christian , Rabaschus Johannes-Samuel , Mütze Thomas , Peuker Urs A.
Published: February 2024

The recycling of lithium-ion batteries, in particular, has become increasingly important in recent years. Due to the materials contained, such as copper or nickel, the return to the economic cycle is important. To ensure this, binding measures have been introduced by the European Commission. As part of the mechanical recycling of lithium-ion batteries, the zig-zag air classifier is used to separate battery components. One application is the separation of the current conductor foils from each other, which is investigated and modelled here. Existing models deriving from the literature are evaluated for material fractions coming from the recycling of different automotive lithium-ion batteries. Since the separation depends on the geometry of the foil particles, similarities for separation depending on the geometric characteristics of the electrodes are derived. It turns out that the material is too complex for the empirical model. However, the model can be used to evaluate the suitability of the apparatus and the quality of the separation.
Vertical Metabolome Transfer from Mother to Child: An Explainable Machine Learning Method for Detecting Metabolomic Heritability
Authors: Lovrić Mario , Horner David , Chen Liang , Brustad Nicklas , Schoos Ann-Marie , Lasky-Su Jessica , Chawes Bo , Rasmussen Morten
Published: February 2024

Vertical transmission of metabolic constituents from mother to child contributes to the manifestation of disease phenotypes in early life. This study probes the vertical transmission of metabolites from mothers to offspring by utilizing machine learning techniques to differentiate between true mother–child dyads and randomly paired non-dyads. Employing random forests (RF), light gradient boosting machine (LGBM), and logistic regression (Elasticnet) models, we analyzed metabolite concentration discrepancies in mother–child pairs, with maternal plasma sampled at 24 weeks of gestation and children’s plasma at 6 months. The propensity of vertical transfer was quantified, reflecting the likelihood of accurate mother–child matching. Our findings were substantiated against an external test set and further verified through statistical tests, while the models were explained using permutation importance and SHapley Additive exPlanations (SHAP). The best model was achieved using RF, while xenobiotics were shown to be highly relevant in transfer. The study reaffirms the transmission of certain metabolites, such as perfluorooctanoic acid (PFOA), but also reveals additional insights into the maternal influence on the child’s metabolome. We also discuss the multifaceted nature of vertical transfer. These machine learning-driven insights complement conventional epidemiological findings and offer a novel perspective on using machine learning as a methodology for understanding metabolic interactions.
Development of Drug Efficacy Testing Platform for Glomerulonephritis
Authors: Kwon Eun-Jeong , Choi Yunyeong , Kim Shin Young , Park Seokwoo , Yun Giae , Min Sei Hong , Kim Sejoong
Published: February 2024

We developed a 3D glomeruli tissue chip for glomerulonephritis (GN) testing, featuring a gravity-driven glomerular filtration barrier (GFB) with human podocytes and endothelial cells with a bidirectional flow in the bottom channel. Using puromycin-induced GN, we observed decreased cell viability, increased albumin permeability, and reduced WT1 and nephrin compared to the normal GFB. Tacrolimus restored cell viability, reduced albumin permeability, and increased WT1 expression. Using serum from five membranous nephropathy (MN) patients, we created MN models using a GFB-mimicking chip. A notable decline in cell viability was observed in the serum-induced MN1 and MN2 models. However, tacrolimus restored it. Albumin permeability was reduced in the MN1, MN2, and MN5 models by tacrolimus treatment. MN1 displayed the best clinical response to tacrolimus, exhibiting increased expression of WT1 in chip-based evaluations after tacrolimus treatment. We successfully evaluated the efficacy of tacrolimus using puromycin-induced and serum-induced GN models on a chip that mimicked the structure and function of the GFB. The GFB-mimicking chip holds promise as a personalized platform for assessing drug efficacy using patient serum samples.
Particle Swarm Optimization of Multilayer Multi-Sized Metamaterial Absorber for Long-Wave Infrared Polarimetric Imaging
Authors: Li Junyu , Li Jinzhao , Yi Fei
Published: February 2024

Infrared polarization imaging holds significant promise for enhancing target recognition in both civil and defense applications. The Division of Focal Plane (DoFP) scheme has emerged as a leading technology in the field of infrared polarization imaging due to its compact design and absence of moving parts. However, traditional DoFP solutions primarily rely on micro-polarizer arrays, necessitating precise alignment with the focal plane array and leading to challenges in alignment and the introduction of optical crosstalk. Recent research has sought to augment the performance of infrared detectors and enable polarization and spectral selection by integrating metamaterial absorbers with the pixels of the detector. Nevertheless, the results reported so far exhibit shortcomings, including low polarization absorption rates and inadequate polarization extinction ratios. Furthermore, there is a need for a comprehensive figure of merit to systematically assess the performance of polarization-selective thermal detectors. In this study, we employ the particle swarm optimization algorithm to present a multilayer, multi-sized metamaterial absorber capable of achieving a remarkable polarization-selective absorption rate of up to 87.2% across the 8–14 μm spectral range. Moreover, we attain a polarization extinction ratio of 38.51. To elucidate and predict the resonant wavelengths of the structure, we propose a modified equivalent circuit model. Our analysis employs optical impedance matching to unveil the underlying mechanisms responsible for the high absorption. We also introduce a comprehensive figure of merit to assess the efficacy of infrared polarization detection through the integration of metamaterials with microbolometers. Finally, drawing on the proposed figure of merit, we suggest future directions for improving integrated metamaterial absorber designs, with the potential to advance practical mid-infrared polarization imaging technologies.
Research on the Reliability of Threshold Voltage Based on GaN High-Electron-Mobility Transistors
Authors: Dai Pengfei , Wang Shaowei , Lu Hongliang
Published: February 2024

With the development of high-voltage and high-frequency switching circuits, GaN high-electron-mobility transistor (HEMT) devices with high bandwidth, high electron mobility, and high breakdown voltage have become an important research topic in this field. It has been found that GaN HEMT devices have a drift in threshold voltage under the conditions of temperature and gate stress changes. Under high-temperature conditions, the difference in gate contact also causes the threshold voltage to shift. The variation in the threshold voltage affects the stability of the device as well as the overall circuit performance. Therefore, in this paper, a review of previous work is presented. Temperature variation, gate stress variation, and gate contact variation are investigated to analyze the physical mechanisms that generate the threshold voltage (VTH) drift phenomenon in GaN HEMT devices. Finally, improvement methods suitable for GaN HEMT devices under high-temperature and high-voltage conditions are summarized.
Bacillus Species: Excellent Biocontrol Agents against Tomato Diseases
Authors: Karačić Vasiljka , Miljaković Dragana , Marinković Jelena , Ignjatov Maja , Milošević Dragana , Tamindžić Gordana , Ivanović Milan
Published: February 2024

Tomatoes encounter many pathogens, such as fungi and bacteria, which reduce the yield and quality of plants and lead to large losses in production. The application of plant protection products (PPPs) is still an important and most effective measure to control plant diseases. However, the use of chemicals in agriculture contributes to environmental pollution and biodiversity loss, and it can also threaten non-target living organisms. Biological control is a widely accessible, environmentally safe, and cost-efficient alternative for the prevention and suppression of plant diseases. Bacillus species with antimicrobial and plant growth-promoting effects are most frequently used as biocontrol agents to increase the resilience of agricultural production against biotic stresses. The present review discusses the antagonistic mechanisms and the biocontrol potential of Bacillus spp. against tomato diseases caused by different pathogens. The main mechanisms of Bacillus spp. include the production of antimicrobial compounds (antibiotics, extracellular enzymes, siderophores, and volatile compounds), competition for nutrients and space, and induced systemic resistance (ISR). Although Bacillus-based PPPs have been developed and commercialised worldwide for various crops and pathogens, the efficiency issues are still subject to debate. Additionally, a combined strategy for controlling tomato diseases based on Bacillus spp. and other available methods (conventional or natural-based) is a promising research field.
Unveiling the Pathological Mechanisms of Death Induced by SARS-CoV-2 Viral Pneumonia
Authors: Oprinca George-Călin , Mohor Cosmin-Ioan , Oprinca-Muja Alexandra , Hașegan Adrian , Cristian Adrian-Nicolae , Fleacă Sorin-Radu , Boeraș Ioana , Cardoș Roxana , Atasie Diter , Mihalache Manuela , Mihalache Cosmin , Tâlvan Elena Teodora , Mohor Călin-Ilie
Published: February 2024

In this comprehensive study of 15 deceased patients with confirmed SARS-CoV-2 infection, spanning a time frame of 1 to 68 days from confirmation to death, autopsies were meticulously conducted with stringent safety measures. Clinical, laboratory, histopathological, and molecular analyses were integrated, shedding light on diverse pulmonary lesions, including acute inflammatory changes, vascular abnormalities, and aberrant regenerative processes. Immunohistochemical analysis, utilizing various markers, successfully identified the SARS-CoV-2 nucleocapsid antigen within infected tissue cells and also revealed what type of inflammatory cells are involved in COVID-19 pathogenesis. Molecular investigations through rt-qPCR revealed the persistent presence and varying quantities of viral genes, even after 68 days. Moreover, the viral nucleocapsid was present even in patients who died after 50 days of infection onset. Employing statistical analyses such as Chi-square and phi coefficient tests, significant associations among microscopic lesions and their correlation with molecular and immunohistochemical findings were elucidated. We could draw a map of what kind of lesions were a direct consequence of viral invasion and what lesions where secondary to the acute immunological response. This integrative approach enhances our understanding of the intricate relationships between pathological features, providing valuable insights into the multifaceted landscape of COVID-19 pathogenesis.
Blastocystis: A Mysterious Member of the Gut Microbiome
Authors: Aykur Mehmet , Malatyalı Erdoğan , Demirel Filiz , Cömert-Koçak Burçak , Gentekaki Eleni , Tsaousis Anastasios D. , Dogruman-Al Funda
Published: February 2024

Blastocystis is the most common gastrointestinal protist found in humans and animals. Although the clinical significance of Blastocystis remains unclear, the organism is increasingly being viewed as a commensal member of the gut microbiome. However, its impact on the microbiome is still being debated. It is unclear whether Blastocystis promotes a healthy gut and microbiome directly or whether it is more likely to colonize and persist in a healthy gut environment. In healthy people, Blastocystis is frequently associated with increased bacterial diversity and significant differences in the gut microbiome. Based on current knowledge, it is not possible to determine whether differences in the gut microbiome are the cause or result of Blastocystis colonization. Although it is possible that some aspects of this eukaryote’s role in the intestinal microbiome remain unknown and that its effects vary, possibly due to subtype and intra-subtype variations and immune modulation, more research is needed to characterize these mechanisms in greater detail. This review covers recent findings on the effects of Blastocystis in the gut microbiome and immune modulation, its impact on the microbiome in autoimmune diseases, whether Blastocystis has a role like bacteria in the gut–brain axis, and its relationship with probiotics.
Gut Microbiota and Biomarkers of Intestinal Barrier Damage in Cirrhosis
Authors: Efremova Irina , Maslennikov Roman , Medvedev Oleg , Kudryavtseva Anna , Avdeeva Anastasia , Krasnov George , Romanikhin Filipp , Diatroptov Mikhail , Fedorova Maria , Poluektova Elena , Levshina Anna , Ivashkin Vladimir
Published: February 2024

Gut dysbiosis and subclinical intestinal damage are common in cirrhosis. The aim of this study was to examine the association of intestinal damage biomarkers (diamine oxidase [DAO], claudin 3, and intestinal fatty acid binding protein [I-FABP; FABP2]) with the state of the gut microbiota in cirrhosis. The blood levels of DAO were inversely correlated with blood levels of claudin 3, lipopolysaccharide (LPS), presepsin, TNF-α, and the severity of cirrhosis according to Child–Pugh scores. The blood level of I-FABP was directly correlated with the blood level of claudin 3 but not with that of DAO. Patients with small intestinal bacterial overgrowth (SIBO) had lower DAO levels than patients without SIBO. There was no significant difference in claudin 3 levels and I-FABP detection rates between patients with and without SIBO. The DAO level was directly correlated with the abundance of Akkermansiaceae, Akkermansia, Allisonella, Clostridiaceae, Dialister, Lactobacillus, Muribaculaceae, Negativibacillus, Ruminococcus, Thiomicrospiraceae, Verrucomicrobiae, and Verrucomicrobiota; and it was inversely correlated with the abundance of Anaerostipes, Erysipelatoclostridium, and Vibrio. The I-FABP level was directly correlated with Anaerostipes, Bacteroidia, Bacteroidota, Bilophila, Megamonas, and Selenomonadaceae; and it was inversely correlated with the abundance of Brucella, Pseudomonadaceae, Pseudomonas, and Vibrionaceae. The claudin 3 level was directly correlated with Anaerostipes abundance and was inversely correlated with the abundance of Brucella, Coriobacteriia, Eggerthellaceae, and Lactobacillus.
Employing Statistical Algorithms and Clustering Techniques to Assess Lithological Facies for Identifying Optimal Reservoir Rocks: A Case Study of the Mansouri Oilfields, SW Iran
Authors: Eftekhari Seyedeh Hajar , Memariani Mahmoud , Maleki Zahra , Aleali Mohsen , Kianoush Pooria , Shirazy Adel , Shirazi Aref , Pour Amin Beiranvand
Published: February 2024

The crucial parameters influencing drilling operations, reservoir production behavior, and well completion are lithology and reservoir rock. This study identified optimal reservoir rocks and facies in 280 core samples from a drilled well in the Asmari reservoir of the Mansouri field in SW Iran to determine the number of hydraulic flow units. Reservoir samples were prepared, and their porosity and permeability were determined by measuring devices. The flow zone index (FZI) was calculated for each sample using MATLAB software; then, a histogram analysis was performed on the logarithmic data of the FZI, and the number of hydraulic flow units was determined based on the obtained normal distributions. Electrical facies were determined based on artificial neural network (ANN) and multi-resolution graph-based clustering (MRGC) approaches. Five electrical facies with dissimilar reservoir conditions and lithological compositions were ultimately specified. Based on described lithofacies, shale and sandstone in zones three and five demonstrated elevated reservoir quality. This study aimed to determine the Asmari reservoir’s porous medium’s flowing fluid according to the C-mean fuzzy logic method. Furthermore, the third and fourth flow units in the Asmari Formation have the best flow units with high reservoir quality and permeability due to determining the siliceous–clastic facies of the rock units and log data. Outcomes could be corresponded to the flow unit determination in further nearby wellbores without cores.
How to Design Human-Vehicle Cooperation for Automated Driving: A Review of Use Cases, Concepts, and Interfaces
Authors: Peintner Jakob , Escher Bengt , Detjen Henrik , Manger Carina , Riener Andreas
Published: February 2024

Currently, a significant gap exists between academic and industrial research in automated driving development. Despite this, there is common sense that cooperative control approaches in automated vehicles will surpass the previously favored takeover paradigm in most driving situations due to enhanced driving performance and user experience. Yet, the application of these concepts in real driving situations remains unclear, and a holistic approach to driving cooperation is missing. Existing research has primarily focused on testing specific interaction scenarios and implementations. To address this gap and offer a contemporary perspective on designing human–vehicle cooperation in automated driving, we have developed a three-part taxonomy with the help of an extensive literature review. The taxonomy broadens the notion of driving cooperation towards a holistic and application-oriented view by encompassing (1) the “Cooperation Use Case”, (2) the “Cooperation Frame”, and (3) the “Human–Machine Interface”. We validate the taxonomy by categorizing related literature and providing a detailed analysis of an exemplar paper. The proposed taxonomy offers designers and researchers a concise overview of the current state of driver cooperation and insights for future work. Further, the taxonomy can guide automotive HMI designers in ideation, communication, comparison, and reflection of cooperative driving interfaces.
Steering of Vortices by Magnetic Field Tilting in Open Superconductor Nanotubes
Authors: Bogush Igor , Fomin Vladimir M. , Dobrovolskiy Oleksandr V.
Published: February 2024

In planar superconductor thin films, the places of nucleation and arrangements of moving vortices are determined by structural defects. However, various applications of superconductors require reconfigurable steering of fluxons, which is hard to realize with geometrically predefined vortex pinning landscapes. Here, on the basis of the time-dependent Ginzburg–Landau equation, we present an approach for the steering of vortex chains and vortex jets in superconductor nanotubes containing a slit. The idea is based on the tilting of the magnetic field B at an angle α in the plane perpendicular to the axis of a nanotube carrying an azimuthal transport current. Namely, while at α=0∘, vortices move paraxially in opposite directions within each half-tube; an increase in α displaces the areas with the close-to-maximum normal component |Bn| to the close(opposite)-to-slit regions, giving rise to descending (ascending) branches in the induced-voltage frequency spectrum fU(α). At lower B values, upon reaching the critical angle αc, the close-to-slit vortex chains disappear, yielding fU of the nf1 type (n≥1: an integer; f1: the vortex nucleation frequency). At higher B values, fU is largely blurry because of multifurcations of vortex trajectories, leading to the coexistence of a vortex jet with two vortex chains at α=90∘. In addition to prospects for the tuning of GHz-frequency spectra and the steering of vortices as information bits, our findings lay the foundation for on-demand tuning of vortex arrangements in 3D superconductor membranes in tilted magnetic fields.
Propagation-Invariant Space–Time Plasmonic Pulse in Subwavelength MIM Waveguide
Authors: Cho Eui-Soo , Lee Seung-Yeol
Published: February 2024

The metal-insulator-metal (MIM) plasmonic waveguide has been highly anticipated for confining and guiding surface plasmon polaritons (SPPs) on the subwavelength scale. However, perennial drawbacks such as a short propagation length and an unbounded transverse field have set limits on the use of the MIM waveguide in various applications. Herein, diffraction- and dispersion-free MIM modes are synthesized by using space–time wave packets (STWPs) and are therefore referred to as space–time MIM (ST-MIM) waveguide modes. Compared to a Gaussian pulse of the same duration and spectral bandwidth, the ST-MIM demonstrates enhanced propagation lengths of about 2.4 times for the symmetric mode and about 6.3 times for the antisymmetric mode. In the simulations, the ST-MIMs are confined in all transverse dimensions, thereby overriding the diffraction limits. In addition, the group velocities of the ST-MIMs can be arbitrarily designed, which makes it possible to synchronize the pulse propagation speeds of the symmetric and antisymmetric MIM modes.
Plasma Treatment of Large-Area Polymer Substrates for the Enhanced Adhesion of UV–Digital Printing
Authors: Fleischer Michal , Kelar Tučeková Zlata , Galmiz Oleksandr , Baťková Eva , Plšek Tomáš , Kolářová Tatiana , Kováčik Dušan , Kelar Jakub
Published: February 2024

UV–digital printing belongs to the commonly used method for custom large-area substrate decoration. Despite low surface energy and adhesion, transparent polymer materials, such as polymethylmethacrylate (PMMA) and polycarbonate (PC), represent an ideal substrate for such purposes. The diffuse coplanar surface barrier discharge (DCSBD) in a novel compact configuration was used for substrate activation to improve ink adhesion to the polymer surface. This industrially applicable version of DCSBD was prepared, tested, and successfully implemented for the UV–digital printing process. Furthermore, wettability and surface free energy measurement, X-ray photoelectron spectroscopy, atomic force, and scanning electron microscopy evaluated the surface chemistry and morphology changes. The changes in the adhesion of the surface and of ink were analyzed by a peel-force and a crosscut test, respectively. A short plasma treatment (1–5 s) enhanced the substrate’s properties of PMMA and PC while providing the pre-treatment suitable for further in-line UV–digital printing. Furthermore, we did not observe damage of or significant change in roughness affecting the substrate’s initial transparency.
Low Adherence to Mediterranean Diet Characterizes Metabolic Patients with Gastrointestinal Cancer
Authors: De Matteis Carlo , Crudele Lucilla , Gadaleta Raffaella Maria , Di Buduo Ersilia , Novielli Fabio , Petruzzelli Stefano , Cariello Marica , Moschetta Antonio
Published: February 2024

Background. Gastrointestinal (GI) cancers are one of the most relevant causes of death globally, frequently associated with poor dietary patterns. The Mediterranean Diet (MedDiet) contributes to cancer prevention. To assess adherence to MedDiet, our research group validated a new score, the Chrono Med Diet Score (CMDS), that captures increased visceral adiposity. Methods. We enrolled 401 subjects who underwent an evaluation for metabolic diseases and specific screening procedures according to current guidelines and were asked to answer CMDS. A total of 71 new cancer cases were recorded, including 40 GI and 31 non-gastrointestinal (NON-GI) cancers. Results. We found that CMDS was reduced in subjects who were diagnosed with cancers. Patients who reported a CMDS score of 12 or less had an over three times increased risk of being diagnosed with GI cancers and presented increased waist circumference and triglycerides and reduced HDL cholesterol compared to adherent subjects. Conclusions. Low CMDS values capture the risk for cancer diagnosis, especially for GI cancers. Thus, CMDS, along with waist circumference, can be considered as a bona fide marker for increased risk of cancer, requiring anticipated screening procedures for the detection of premalignant and early stage GI cancers in patients with low adherence to MedDiet.
Thermodynamic Analysis to Evaluate the Effect of Diet on Brain Glucose Metabolism: The Case of Fish Oil
Authors: Yildiz Cennet , Medina Isabel
Published: February 2024

Inefficient glucose metabolism and decreased ATP production in the brain are linked to ageing, cognitive decline, and neurodegenerative diseases (NDDs). This study employed thermodynamic analysis to assess the effect of fish oil supplementation on glucose metabolism in ageing brains. Data from previous studies on glucose metabolism in the aged human brain and grey mouse lemur brains were examined. The results demonstrated that Omega-3 fish oil supplementation in grey mouse lemurs increased entropy generation and decreased Gibbs free energy across all brain regions. Specifically, there was a 47.4% increase in entropy generation and a 47.4 decrease in Gibbs free energy in the whole brain, indicating improved metabolic efficiency. In the human model, looking at the specific brain regions, supplementation with Omega-3 polyunsaturated fatty acids (n-3 PUFAs) reduced the entropy generation difference between elderly and young individuals in the cerebellum and particular parts of the brain cortex, namely the anterior cingulate and occipital lobe, with 100%, 14.29%, and 20% reductions, respectively. The Gibbs free energy difference was reduced only in the anterior cingulate by 60.64%. This research underscores that the application of thermodynamics is a comparable and powerful tool in comprehending the dynamics and metabolic intricacies within the brain.
Food Security and Health Outcomes following Gray Divorce
Authors: Zhao Hang , Andreyeva Tatiana , Sun Xiaohan
Published: February 2024

The study evaluates the immediate and long-term consequences of gray divorce (i.e., marital dissolution after age 50) for the food security, depression, and disability of older Americans. Staggered Difference-in-Difference models were fitted to a nationally representative longitudinal sample of adults aged ≥ 50 years from the Health and Retirement Study, 1998–2018. Food insecurity and disability increase in the year of gray divorce and remain significantly elevated for up to six years or more following the event, consistent with the chronic strain model of gray divorce. Gray divorce has particularly adverse consequences for the food security of older women, while no gender differences were observed for disability. Increasing trends in gray divorce have important negative implications for food security and health of older Americans, particularly women, who appear to be less prepared to financially withstand a marital collapse in older age. Targeted policies to provide nutrition assistance and support in reemployment might be necessary to reduce the burden of food insecurity in the wake of gray divorce among women.
Relationship between Eating Alone and Handgrip Strength in Korean Older Adults
Authors: Yoo Min Young , Song Hong Ji , Park Kyung Hee , Seo Young-Gyun , An Hye-Ji , Paek Yu-Jin , Noh Hye-Mi
Published: February 2024

Sarcopenia is defined as an age-related decline in muscle mass, muscle strength, and physical performance. Eating alone has been linked to various health issues in older adults. This study investigated the relationship between eating alone and handgrip strength (HGS) in older adults using data from 7278 individuals (≥65 years) who participated in the 2014–2019 Korea National Health and Nutrition Examination Survey. HGS was measured using a digital grip strength dynamometer, relative HGS was calculated by dividing HGS by body mass index, and dynapenia was defined as an HGS < 28 kg for men and <18 kg for women. Multivariable logistic regression analysis showed that women who ate two meals alone were more likely to exhibit dynapenia than those who never ate alone (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.03–1.77). If the groups that never ate alone or ate one meal alone were combined as the reference group, the probability of dynapenia was higher in the combined groups that ate two or three meals alone (OR, 1.25; 95% CI, 1.04–1.50). No association was observed between eating alone and dynapenia in men. This suggests that eating alone is a modifiable related factor of dynapenia in older women.
Impact of Intensive Lifestyle Intervention on Remission of Metabolic Syndrome, Prediabetes, Diabetes, and Hypertension in Adults Living with Obesity
Authors: Magnan Pierre-Olivier , Iglesies-Grau Josep , Latour Élise , Guilbeault Valérie , Nigam Anil , Juneau Martin , Bherer Louis , Gayda Mathieu
Published: February 2024

Background: Lifestyle intervention programs have long been shown to be effective in preventing cardiometabolic risk factors (CMRFs) such as metabolic syndrome (MS), impaired fasting glycaemia (IFG), type II diabetes (T2DM), and hypertension (HTA). However, their potential for remission of these CMRFs in overweight/obese adults is less clear. The importance of attaining remission has significantly increased as these CMRFs are more and more prevalent. Objectives: The aim of this study is to determine the impact of an intensive lifestyle intervention program on the remission of MS, IFG, T2DM, and HTA in overweight/obese adults. Methods: Forty participants living with overweight/obesity were enrolled in an 18-month multidisciplinary primary prevention body mass loss intervention program. MS, IFG, T2DM, and HTA statuses were assessed at baseline, 9 months, and the end of the program. Results: At baseline, 25 participants (64.1%) had MS, 7 (17.9%) had IFG, 4 (10.2%) were living with diabetes, and 28 (70.0%) had HTA. At 18 months, six (24%) of the participants living with MS, two (28.6%) of the participants with IFG, two (50%) of the participants with diabetes, and two (7.1%) of the participants with HTA met all criteria for remission. Conclusion: An intensive lifestyle intervention program consisting of monitored exercise training and lifestyle modification counselling has great potential for achieving remission of CMRFs in adults living with overweight/obesity.
Antibacterial Activity and Mechanisms of Plant Flavonoids against Gram-Negative Bacteria Based on the Antibacterial Statistical Model
Authors: Yan Yu , Xia Xuexue , Fatima Aiman , Zhang Li , Yuan Ganjun , Lian Fengxian , Wang Yu
Published: February 2024

The antimicrobial quantitative structure–activity relationship of plant flavonoids against Gram-positive bacteria was established in our previous works, and the cell membrane was confirmed as a major site of action. To investigate whether plant flavonoids have similar antibacterial effects and mechanisms against both Gram-negative and Gram-positive bacteria, here, the minimum inhibitory concentrations (MICs) of 37 plant flavonoids against Escherichia coli were determined using the microdilution broth method, and then the correlation between their lipophilic parameter ACD/LogP or LogD7.40 value and their MIC was analyzed. Simultaneously, the correlation between the ACD/LogP or LogD7.40 value and the MIC of 46 plant flavonoids reported in the literature against E. coli was also analyzed. Both sets of results showed that there is a significant correlation between the LogP value and the MIC of plant flavonoids against Gram-negative bacteria. However, it is difficult to effectively predict the MIC of plant flavonoids against Gram-negative bacteria from their lipophilic parameters. By comparing two regression curves derived from plant flavonoids against Gram-negative and Gram-positive bacteria, it was further discovered that the antibacterial activities of most plant flavonoids against Gram-negative bacteria are stronger than those against Gram-positive bacteria when their LogP values are less than approximately 3.0, but the opposite is true when their LogP values are more than approximately 3.6. Moreover, this comparison also suggests that unlike mainly acting on the cell membrane of Gram-positive bacteria, plant flavonoids have multiple mechanisms against Gram-negative species, while the cell membrane is also an important action site among them. Combined with the correlation analyses between the enzyme inhibitory activity and the LogP value of the reported flavonoids, it was further suggested that DNA gyrase is another important target of plant flavonoids against Gram-negative bacteria.
A Drug Safety Briefing (II) in Transplantation from Real-World Individual Pharmacotherapy Management to Prevent Patient and Graft from Polypharmacy Risks at the Very Earliest Stage
Authors: Wolf Ursula
Published: February 2024

For early and long-term patient and graft survival, drug therapy in solid organ and hematopoietic stem cell transplantation inevitably involves polypharmacy in patients with widely varying and even abruptly changing conditions. In this second part, relevant medication briefing is provided, in addition to the scores defined in the previously published first part on the design of the Individual Pharmacotherapy Management (IPM). The focus is on the growing spectrum of contemporary polypharmacy in transplant patients, including early and long-term follow-up medications. 1. Unlike the available drug–drug interaction (DDI) tables, for the first time, this methodological all-in-one device refers to the entire risks, including contraindications, special warnings, adverse drug reactions (ADRs), and DDIs. The selection of 65 common critical drugs results from 10 years of daily IPM with real-world evidence from more than 60,800 IPM inpatient and outpatient medication analyses. It includes immunosuppressants and typical critical antimicrobials, analgesics, antihypertensives, oral anticoagulants, antiarrhythmics, antilipids, antidepressants, antipsychotics, antipropulsives, antiemetics, propulsives, proton pump inhibitors (PPIs), sedatives, antineoplastics, and protein kinase inhibitors. As a guide for the attending physician, the drug-related risks are presented in an alphabetical overview based on the Summaries of Product Characteristics (SmPCs) and the literature. 2. Further briefing refers to own proven clinical measures to manage unavoidable drug-related high-risk situations. Drug-induced injuries to the vulnerable graft and the immunosuppressed comorbid patient require such standardized, intensive IPM and the comprehensive preventive briefing toolset to optimize the outcomes in the polypharmacy setting.
An Inulin-Type Fructan CP-A from Codonopsis pilosula Alleviated 5-Fluorouracil-Induced Intestinal Mucositis via the ERK/MLCK/MLC2 Pathway and Regulation of Gut Microbiota
Authors: Zhou Jiangtao , Li Deyun , Wang Jiajing , Cheng Zhuoyang , Wang Changjian , Zhang Xuepeng , Xu Xiexin , Gao Jianping
Published: February 2024

Intestinal mucositis (IM) is a common adverse effect of chemotherapy, limiting its clinical application. Codonopsis pilosula-derived CP-A (an inulin-type fructan) is an edible Chinese medicine with anti-inflammatory and gastrointestinal protective effects, which may be useful for treating IM. Here, we explored CP-A’s role in ameliorating IM induced by 5-fluorouracil (5-FU) and investigated the underlying mechanism using in vitro experiments and rat models. Western blotting, immunohistochemistry (IHC), and real-time PCR (RT-PCR) analyses were used to assess protein expression related to the extracellular-regulated protein kinases (ERK)/myosin light chain kinase (MLCK)/myosin light chain 2 (MLC2) signaling pathway and tight junction proteins. Inflammatory factors were quantified using enzyme-linked immunosorbent assays (ELISAs), and 16S rRNA amplicon sequencing was employed for cecum content analysis. The results indicated that CP-A restored body weight and food intake and reversed histopathological changes in IM rats. Further, abnormal MLCK activation induced by 5-FU was attenuated by CP-A via the ERK/MLCK/MLC2 pathway. CP-A treatment improved tight junction protein levels and reduced inflammatory factor expression. Moreover, CP-A intervention regulated the intestinal microbiota community structure, increasing the abundance of Lactobacillus and decreasing the abundance of Shigella. In conclusion, CP-A mitigates 5-FU-induced IM by inhibiting the ERK/MLCK/MLC2 pathway, reducing the expression of inflammatory factors, improving the intestinal mucosal barrier, and regulating the intestinal microbial community. This study highlights CP-A’s therapeutic potential in IM treatment and provides insights for future research.
Implications of NLRP3 Suppression Using Glibenclamide and miR-223 against Colorectal Cancer
Authors: Hamza Shaimaa , Garanina Ekaterina E. , Shkair Layaly , Alsaadi Mohammad , Khaiboullina Svetlana F. , Tezcan Gulcin
Published: February 2024

The NLR family pyrin domain containing 3 (NLRP3) promotes the growth of colorectal cancer (CRC). However, the therapeutic effect of NLRP3 inhibition on CRC cell progression is controversial. This study comparatively investigated the therapeutic effect of a pharmacological NLRP3 inhibitor, glibenclamide (gli), and the post-translational suppression of NLRP3 by miR-223 on CRC cell progression in HCT-116 and HCT-15 cells. LPS and ATP were used to activate Gli-treated and LSB-hsa-miR-223-3p (WTmiR-223)-expressing HCT-116 cells. NLRP3.AB.pCCL.sin.cPPT.U6.miR-223-Decoy.hPGK.GFP.WPRE plasmid (DmiR-223) was the negative control for miR-223 expression. NLRP3, gasdermin D, and BAX expressions were analyzed using western blotting. Real-time PCR detected the RNA expression of autophagy-related genes ATG5, BECN1, and miR-223 in non-transfected cells. ELISA analyzed IL-1β and IL-18 in the medium. MTS-1, annexin V, wound-healing, and sphere-invasion assays were used to assess cell viability and progression. A multiplex cytokine assay detected proinflammatory cytokine secretion. LPS–ATP-activated NLRP3 produced gasdermin D cleavage, released IL-1b and IL-18, and activated cell migration and sphere invasion. In contrast, reduced cell growth, miR-223 expression, IFN-γ, CXCL10, and LIF secretion were found in cells after inflammasome activation. Both gli and WTmiR-223 induced autophagy genes ATG5 and BECN1 and reduced the NLRP3 activation and its downstream proteins. However, while gli had a limited effect on the production of IFN-γ, CXCL10, and LIF, WTmiR-223 increased the release of those cytokines. In addition, gli did not suppress cell growth, while WTmiR-223 promoted apoptosis. Notably, neither gli nor WTmiR-223 effectively prevented sphere invasion. These data suggest that, while WTmiR-223 could have a better anticancer effect in CRC compared to gli, the sole usage of miR-223-mediated NLRP3 suppression may not be sufficient to prevent CRC metastasis.
Pharmacokinetic Interaction of Kratom and Cannabidiol in Male Rats
Authors: Berthold Erin C. , Kamble Shyam H. , Kanumuri Siva Rama Raju , Kuntz Michelle A. , Senetra Alexandria S. , Chiang Yi-Hua , Mukhopadhyay Sushobhan , McCurdy Christopher R. , Sharma Abhisheak
Published: February 2024

Kratom and cannabidiol products are used to self-treat a variety of conditions, including anxiety and pain, and to elevate mood. Research into the individual pharmacokinetic properties of commercially available kratom and cannabidiol products has been performed, but there are no studies on coadministration of these products. Surveys of individuals with kratom use history indicate that cannabidiol use is one of the strongest predictors of both lifetime and past month kratom use. The purpose of this study was to determine if there are changes in pharmacokinetic properties when commercially available kratom and cannabidiol products are administered concomitantly. It was found that with concomitant administration of cannabidiol, there was a 2.8-fold increase in the exposure of the most abundant kratom alkaloid, mitragynine, and increases in the exposure of other minor alkaloids. The results of this work suggest that with cannabidiol coadministration, the effects of kratom may be both delayed and increased due to a delay in time to reach maximum plasma concentration and higher systemic exposure of the psychoactive alkaloids found in kratom.