bluuebunny/crossref_metadata_2025 huggingface dataset:
Advancing High-Performance Metal Matrix Composites: Uniting Nature’s Design and Engineering Innovation
Authors: Sadeghi Behzad
Published: September 2023

We are pleased to present this Special Issue entitled “Advanced High-Performance Metal Matrix Composites (MMCs),” which explores promising materials science that will change everything from aerospace to automotive technology [...]
Bisphosphonates and Dental Implants: A Systematic Review and Meta-Analysis
Authors: Sulaiman Nabaa , Fadhul Fadi , Chrcanovic Bruno Ramos
Published: September 2023

The purpose of the present systematic review was to investigate the influence of bisphosphonates (BPs) on the dental implant failure rate and marginal bone loss (MBL). An electronic search was undertaken in three databases, plus a manual search of journals. Meta-analyses were performed, besides a meta-regression in order to verify how the log odds ratio (OR) was associated with follow-up time. The five- and ten-year estimated implant survivals were calculated. The review included 33 publications. Altogether, there were 1727 and 21,986 implants placed in patients taking and not taking BPs, respectively. A pairwise meta-analysis (26 studies) showed that implants in BP patients had a higher failure risk in comparison to non-BP patients (OR 1.653, p = 0.047). There was an estimated decrease of 0.004 in log OR for every additional month of follow-up, although it was not significant (p = 0.259). The global estimated implant survival in patients taking BPs after 5 and 10 years was 94.2% (95% CI, 94.0–94.4) and 90.1% (95% CI, 89.8–90.3), respectively. It was not possible to make any reliable analysis concerning MBL, as only two studies reported MBL results separated by groups. There is a 65.3% higher risk of implant failure in patients taking BPs in comparison to patients not taking this class of drugs.
Discontinuous Control Algorithm for Buck Converter under Time-Varying Load and Input Voltage
Authors: Krasnova Svetlana A. , Kochetkov Sergey , Utkin Victor A.
Published: September 2023

In this paper, the problem of the output voltage regulation of buck converters is considered. The novelty of the problem statement is that the external electric load and the input voltage of the converter are unknown bounded functions of a certain class. In particular, the external load equivalent scheme is similar to the successive connection of the inductive and resistive elements. In this case, the behavior of the load current is described by the differential equation with time-varying coefficients. In this equation, the equivalent inductance and resistance are described by unknown arbitrary bounded functions with several bounded derivatives. Under known bounds for these functions and their derivatives, the initial system can be transformed into the special form with smooth bounded perturbation. This disturbance is an unknown function, and its action channel differs from the input channel. Therefore, the influence on the unknown external load can not be compensated for directly by the control input. Due to this reason, the new control strategy is developed in the paper with the help of a “vortex” algorithm, which provides asymptotic convergence of the regulation error to zero in time. How to choose the converter parameters and the bounds for the input voltage to operate the closed-loop system properly are shown. The convergence proof is organized with the help of the Lyapunov function approach, and the transient rate is also estimated. The simulation results show the efficiency of the designed control law for the wide class of input voltage and electrical parameter functions. The proposed control scheme may be further used in electric drive systems.
Classification of Motor Imagery Using Trial Extension in Spatial Domain with Rhythmic Components of EEG
Authors: Molla Md. Khademul Islam , Ahamed Sakir , Almassri Ahmed M. M. , Wagatsuma Hiroaki
Published: September 2023

Electrical activities of the human brain can be recorded with electroencephalography (EEG). To characterize motor imagery (MI) tasks for brain–computer interface (BCI) implementation is an easy and cost-effective tool. The MI task is represented by a short-time trial of multichannel EEG. In this paper, the signal of each channel of raw EEG is decomposed into a finite set of narrowband signals using a Fourier-transformation-based bandpass filter. Rhythmic components of EEG are represented by each of the narrowband signals that characterize the brain activities related to MI tasks. The subband signals are arranged to extend the dimension of the EEG trial in the spatial domain. The spatial features are extracted from the set of extended trials using a common spatial pattern (CSP). An optimum number of features are employed to classify the motor imagery tasks using an artificial neural network. An integrated approach with full-band and narrowband signals is implemented to derive discriminative features for MI classification. In addition, the subject-dependent parameter optimization scheme enhances the performance of the proposed method. The performance evaluation of the proposed method is obtained using two publicly available benchmark datasets (Dataset I and Dataset II). The experimental results in terms of classification accuracy (93.88% with Dataset I and 91.55% with Dataset II) show that it performs better than the recently developed algorithms. The enhanced MI classification accuracy is very much applicable in BCI implementation.
Automatic Piston-Type Flow Standard Device Calibration System
Authors: Song Xinming , Wang Xiaoli , Ma Min
Published: September 2023

Measurement of flow is crucial for assuring product quality, increasing manufacturing effectiveness, and promoting the development of science and technology. With the advancement of calibration and automation, standard devices using the mass method, volumetric method, and master meter method have limitations, such as low calibration efficiency and automation, large size, and complex operation. Innovations in this area are desperately needed. To realize the automation of calibrating ultrasonic water meters, a piston-type flow standard device calibration system with a high degree of automation, high calibration efficiency, small size, and easy operation was designed. A piston-type flow standard device was designed, the standard device was modeled, the selection of the main hardware and the design of the automated control of the hardware parts were completed; an automation control system adapted to the flow standard device was developed; and, furthermore, a water meter flow point calibration algorithm integrating the start–stop method and the dual-time method, as well as a water meter flow correction algorithm, was devised to improve the efficiency of ultrasonic water meter calibration. An uncertainty assessment of the designed system was completed; the standard uncertainty and expanded uncertainty of the device were 0.013% and 0.026%. Meanwhile, flow calibration tests were conducted, validating the rationality of the automated calibration algorithm for ultrasonic water meters. The results show that ultrasonic water meters calibrated with flow correction have a flow error within ±3% in the “low flow range” and within ±2% in the “high flow range”, with a repeatability of less than 0.05%. This indicates that a piston-type flow standard device, coupled with an automation calibration control system, can efficiently, accurately, and conveniently perform water meter calibration, and the system has good practical value.
Probabilistic Slope Stability Analysis of Mount St. Helens Using Scoops3D and a Hybrid Intelligence Paradigm
Authors: Kumar Sumit , Choudhary Shiva Shankar , Burman Avijit , Singh Raushan Kumar , Bardhan Abidhan , Asteris Panagiotis G.
Published: September 2023

In the past, numerous stratovolcanoes worldwide witnessed catastrophic flank collapses. One of the greatest risks associated with stratovolcanoes is a massive rock failure. On 18 May 1980, we witnessed a rock slope failure due to a volcano eruption, and a 2185.60 m high rock slope of Mount St. Helens was collapsed. Thus, from the serviceability perspective, this work presents an effective computational technique to perform probabilistic analyses of Mount St. Helens situated in Washington, USA. Using the first-order second-moment method, probability theory and statistics were employed to map the uncertainties in rock parameters. Initially, Scoops3D was used to perform slope stability analysis followed by probabilistic evaluation using a hybrid computational model of artificial neural network (ANN) and firefly algorithm (FF), i.e., ANN-FF. The performance of the ANN-FF model was examined and compared with that of conventional ANN and other hybrid ANNs built using seven additional meta-heuristic algorithms. In the validation stage, the proposed ANN-FF model was the best-fitted hybrid model with R2 = 0.9996 and RMSE = 0.0042. Under seismic and non-seismic situations, the reliability index and the probability of failure were estimated. The suggested method allows for an effective assessment of the failure probability of Mount St. Helens under various earthquake circumstances. The developed MATLAB model is also attached as a supplementary material for future studies.
Risk Factors Associated with Failure and Technical Complications of Implant-Supported Single Crowns: A Retrospective Study
Authors: Larsson Adam , Manuh Justice , Chrcanovic Bruno Ramos
Published: September 2023

Background and Objectives: Implant-supported single crowns have become a routine approach for the replacement of missing single teeth, being considered as one of the most common ways of rehabilitation when adjacent teeth are healthy. The present retrospective study aimed to investigate the risk factors possibly associated with failure and technical complications of implant-supported single crowns and their supporting implants. Materials and Methods: Patients treated at one faculty (2009–2019) were considered for inclusion. Complications investigated included ceramic fracture/chipping, crown loss of retention/mobility, crown failure/fracture, loosening/loss/fracture of prosthetic screw, and implant failure/fracture. Any condition/situation that led to the removal/replacement of crowns (implant failure not included) was considered prosthesis failure. Univariate/multivariate Cox regression models were used to evaluate the associations between clinical covariates and failure. Results: 278 patients (358 crowns) were included. Mean ± SD follow-up was 56.5 ± 29.7 months. Seven implants (after a mean of 76.5 ± 43.7 months) and twenty crowns (21.3 ± 23.5 months) failed. The cumulative survival rate (CSR) for crowns was 93.5% after 5, remaining at 92.2% between 6 and 11 years. The most common reasons for crown failure were porcelain large fracture (n = 6), crown repeatedly loose (n = 6), and porcelain chipping (n = 5). Men and probable bruxism were identified in the Cox regression model as being associated with crown failure. The most common observed technical complications were mobility of the crown and chipping of the ceramic material, with the latter being observed even in crowns manufactured of monolithic zirconia. Cases with at least one technical complication (not considering loss of screw hole sealing) were more common among probable bruxers than in non-bruxers (p = 0.002). Cases of ceramic chipping were more common among bruxers than in non-bruxers (p = 0.014, log-rank test). Conclusions: Probable bruxism and patient’s sex (men) were factors associated with a higher risk of failure of implant-supported single crowns.
Time-Course Lipidomics of Ornithine-Induced Severe Acute Pancreatitis Model Reveals the Free Fatty Acids Centered Lipids Dysregulation Characteristics
Authors: Yang Jinxi , Wang Manjiangcuo , Qiu Qi , Huang Yan , Wang Yiqin , Pu Qianlun , Jiang Na , Wang Rui , Wen Li , Zhang Xiaoying , Han Chenxia , Du Dan
Published: September 2023

The relationship between the type and intensities of lipids of blood and pancreas and the pathological changes in the pancreas during severe acute pancreatitis (SAP) remains unclear. In our study, we employed a rat model of SAP induced through intraperitoneal ornithine injections. We collected serum and pancreas samples at various time points (0–144 h) for histopathological and biochemical assessments, followed by lipidomic analyses using LC-MS/MS or in situ mass spectrometry imaging (MSI) To discern changes over time or at specific points, we employed time-course and univariate analyses for lipid screening, respectively. Our findings indicated that the peak inflammation in the Orn-SAP model occurred within the 24–30 h timeframe, with evident necrosis emerging from 24 h onwards, followed by regeneration starting at 48 h. Time-course analysis revealed an overall decrease in glycerophospholipids (PEs, PCs, LPEs, LPCs), while CEs exhibited an increase within the pancreas. Univariate analysis unveiled a significant reduction in serum TAGs containing 46–51 carbon atoms at 24 h, and CERs in the pancreas significantly increased at 30 h, compared with 0 h. Moreover, a substantial rise in TAGs containing 56–58 carbon atoms was observed at 144 h, both in serum and pancreas. MSI demonstrated the CERs containing saturated mono-acyl chains of 16 and 18 carbon atoms influenced pancreatic regeneration. Tracing the origin of FFAs hydrolyzed from pancreatic glycerophospholipids and serum TAGs during the early stages of inflammation, as well as FFAs utilized for CEs and CERs synthesis during the repair phase, may yield valuable strategies for diagnosing and managing SAP.
Transcriptional and Metabolic Profiling of Arabidopsis thaliana Transgenic Plants Expressing Histone Acetyltransferase HAC1 upon the Application of Abiotic Stress—Salt and Low Temperature
Authors: Ivanova Tatiana , Dincheva Ivayla , Badjakov Ilian , Iantcheva Anelia
Published: September 2023

Augmented knowledge of plant responses upon application of stress could help improve our understanding of plant tolerance under abiotic stress conditions. Histone acetylation plays an important role in gene expression regulation during plant growth and development and in the response of plants to abiotic stress. The current study examines the level of transcripts and free metabolite content in transgenic Arabidopsis thaliana plants expressing a gene encoding histone acetyltransferase from Medicago truncatula (MtHAC1) after its heterologous expression. Stable transgenic plants with HAC1 gain and loss of function were constructed, and their T5 generation was used. Transgenic lines with HAC1-modified expression showed a deviation in root growth dynamics and leaf area compared to the wild-type control. Transcriptional profiles were evaluated after the application of salinity stress caused by 150 mM NaCl at four different time points (0, 24, 48, and 72 h) in treated and non-treated transgenic and control plants. The content and quantity of free metabolites—amino acids, mono- and dicarbohydrates, organic acids, and fatty acids—were assessed at time points 0 h and 72 h in treated and non-treated transgenic and control plants. The obtained transcript profiles of HAC1 in transgenic plants with modified expression and control were assessed after application of cold stress (low temperature, 4 °C).
No City Left Behind: Building Climate Policy Bridges between the North and South
Authors: Hachaichi Mohamed
Published: September 2023

Cities are progressively heightening their climate aspirations to curtail urban carbon emissions and establish a future where economies and communities can flourish within the Earth’s ecological limits. Consequently, numerous climate initiatives are being launched to control urban carbon emissions, targeting various sectors, including transport, residential, agricultural, and energy. However, recent scientific literature underscores the disproportionate distribution of climate policies. While cities in the Global North have witnessed several initiatives to combat climate change, cities in the Global South remain uncovered and highly vulnerable to climate hazards. To address this disparity, we employed the Balanced Iterative Reducing and Clustering using the Hierarchies (BRICH) algorithm to cluster cities from diverse geographical areas that exhibit comparable socioeconomic profiles. This clustering strives to foster enhanced cooperation and collaboration among cities globally, with the goal of addressing climate change in a comprehensive manner. In summary, we identified similarities, patterns, and clusters among peer cities, enabling mutual and generalizable learning among worldwide peer-cities regarding urban climate policy exchange. This exchange occurs through three approaches: (i) inner-mutual learning, (ii) cross-mutual learning, and (iii) outer-mutual learning. Our findings mark a pivotal stride towards attaining worldwide climate objectives through a shared responsibility approach. Furthermore, they provide preliminary insights into the implementation of “urban climate policy exchange” among peer cities on a global scale.
The Effects of Airflow on the Mechanosensitive Channels of Escherichia coli MG1655 and the Impact of Survival Mechanisms Triggered
Authors: Ramirez Violette I. , Wray Robin , Blount Paul , King Maria D.
Published: September 2023

Understanding how bacteria respond to ventilated environments is a crucial concept, especially when considering accurate airflow modeling and detection limits. To properly design facilities for aseptic conditions, we must minimize the parameters for pathogenic bacteria to thrive. Identifying how pathogenic bacteria continue to survive, particularly due to their multi-drug resistance characteristics, is necessary for designing sterile environments and minimizing pathogen exposure. A conserved characteristic among bacterial organisms is their ability to maintain intracellular homeostasis for survival and growth in hostile environments. Mechanosensitive (MS) channels are one of the characteristics that guide this phenomenon. Interestingly, during extreme stress, bacteria will forgo favorable homeostasis to execute fast-acting survival strategies. Physiological sensors, such as MS channels, that trigger this survival mechanism are not clearly understood, leaving a gap in how bacteria translate physical stress to an intracellular response. In this paper, we study the role of mechanosensitive ion channels that are potentially triggered by aerosolization. We hypothesize that change in antimicrobial uptake is affected by aerosolization stress. Bacteria regulate their defense mechanisms against antimicrobials, which leads to varying susceptibility. Based on this information we hypothesize that aerosolization stress affects the antimicrobial resistance defense mechanisms of Escherichia coli (E. coli). We analyzed the culturability of knockout E. coli strains with different numbers of mechanosensitive channels and compared antibiotic susceptibility under stressed and unstressed airflow conditions. As a result of this study, we can identify how the defensive mechanisms of resistant bacteria are triggered for their survival in built environments. By changing ventilation airflow velocity and observing the change in antibiotic responses, we show how pathogenic bacteria respond to ventilated environments via mechanosensitive ion channels.
Co-Circulation of SARS-CoV-2 and Other Respiratory Pathogens in Upper and Lower Respiratory Tracts during Influenza Season 2022–2023 in Lazio Region
Authors: Bordi Licia , Vulcano Antonella , Sberna Giuseppe , Nonis Marino , Giacomini Paolo , Maggi Fabrizio , Fontana Carla , Lalle Eleonora
Published: September 2023

Lower respiratory tract infections (LRTIs) occur when there is a lower airway tract infection. They are well-known for increasing the susceptibility of patients to bacterial/fungal co-infections and super-infections. In this study, we present the results of our investigation, which involved 381 consecutive patients admitted to our hospital during the Influenza season from October 2022 to April 2023. Among the 381 specimens, 75 were bronchoalveolar (BAL), and 306 were nasopharyngeal swabs (NPSs). Notably, 34.4% of the examined samples tested positive for SARS-CoV-2. Of these, we observed that 7.96% of NPSs showed positivity only for other respiratory viruses, while a substantial percentage (77%) of BAL specimens exhibited positive results only for bacterial co-infections. The results of our study not only confirm the importance of co-infections in COVID-19 but also emphasize the significance of utilizing rapid diagnostic tests (RDTs) for the timely diagnosis of LRTIs. In fact, RDTs allow for the identification of multiple pathogens, providing clinicians with useful and timely information to establish effective therapy.
Nanoparticles Carrying Conserved Regions of Influenza A Hemagglutinin, Nucleoprotein, and M2 Protein Elicit a Strong Humoral and T Cell Immune Response and Protect Animals from Infection
Authors: Zykova Anna A. , Blokhina Elena A. , Stepanova Liudmila A. , Shuklina Marina A. , Ozhereleva Olga O. , Tsybalova Liudmila M. , Kuprianov Victor V. , Ravin Nikolai V.
Published: September 2023

Current influenza vaccines are mainly strain-specific and have limited efficacy in preventing new influenza A strains. Efficient control of infection can potentially be achieved through the development of broad-spectrum vaccines based on conserved antigens. A combination of several such antigens, including the conserved region of the second subunit of the hemagglutinin (HA2), the extracellular domain of the M2 protein (M2e), and epitopes of nucleoprotein (NP), which together can elicit an antibody- and cell-mediated immune response, would be preferred for vaccine development. In this study, we obtained recombinant virus-like particles formed by an artificial self-assembling peptide (SAP) carrying two epitopes from NP, tandem copies of M2e and HA2 peptides, along with a T helper Pan DR-binding epitope (PADRE). Fusion proteins expressed in Escherichia coli self-assembled in vitro into spherical particles with a size of 15–35 nm. Immunization of mice with these particles induced strong humoral immune response against M2e and the entire virus, and lead to the formation of cytokine-secreting antigen-specific CD4+ and CD8+ effector memory T cells. Immunization provided high protection of mice against the lethal challenge with the influenza A virus. Our results show that SAP-based nanoparticles carrying conserved peptides from M2, HA, and NP proteins of the influenza A virus, as well as T helper epitope PADRE, can be used for the development of universal flu vaccines.
N-Doped Graphene Quantum Dots Confined within Silica Nanochannels for Enhanced Electrochemical Detection of Doxorubicin
Authors: Zhang Chaoyan , Zhou Xiaoyu , Yan Fei , Lin Jing
Published: September 2023

Herein, we describe a fast and highly sensitive electrochemical sensor for doxorubicin (DOX) detection based on the indium tin oxide (ITO) modified with a binary material consisting of vertically-ordered mesoporous silica films (VMSFs) and N-doped graphene quantum dots (NGQDs). VMSFs, with high permeability and efficient molecular transport capacity, is attached to the ITO electrode via a rapid and controllable electrochemical method, which can serve as a solid template for the confinement of numerous NGQDs through facile electrophoresis. By virtue of the excellent charge transfer capacity, π-π and electrostatic preconcentration effects of NGQDs, as well as the electrostatic enrichment ability of VMSF, the presented NGQDs@VMSF/ITO shows amplified electrochemical signal towards DOX with a positive charge, resulting in good analytical performance in terms of a wide linear range (5 nM~0.1 μM and 0.1~1 μM), high sensitivity (30.4 μA μM−1), and a low limit of detection (0.5 nM). Moreover, due to the molecular sieving property of VMSF, the developed NGQDs@VMSF/ITO sensor has good selectivity and works well in human serum and urine samples, with recoveries of 97.0~109%, thus providing a simple and reliable method for the direct electrochemical analysis of DOX without complex sample pretreatment procedures.
Characterization of Olive Oil Volatile Compounds after Elution through Selected Bleaching Materials—Gas Chromatography–Mass Spectrometry Analysis
Authors: Al-Dabbas Maher M. , Al-Jaloudi Rawan , Abdullah Mai Adnan , Abughoush Mahmoud
Published: September 2023

Using different bleaching materials to eliminate or reduce organic volatiles in deteriorated olive oils will positively affect its characteristics. This study aims to identify the volatiles of oxidized olive oil after physical bleaching using selected immobilized adsorbents. Oxidized olive oil was eluted using open-column chromatography packed with silica gel, bentonite, resin, Arabic gum, and charcoal at a 1:5 eluent system (w/v, adsorbent: oxidized olive oil). The smoke point was determined. The collected distilled vapor was injected into GC-MS to identify the volatiles eluted after partial refining with each of these bleaching compounds. The results showed that volatile compounds were quantitatively and qualitatively affected by the type of adsorbents used for the elution of olive oil and the smoking points of eluted oils. The most prominent detected volatile compounds were limonene (14.53%), piperitone (10.35%), isopropyl-5-methyl-(2E)-hexenal (8.6%), methyl octadecenoate (6.57%), and citronellyl acetate (5.87%). Both bentonite and resin were superior in decreasing the ratio of volatile compounds compared with other bleaching materials used. Resin immobilized medium was significantly affected (p < 0.05), raising the smoke point. These results highlighted some information regarding the characteristics of volatile compounds that result after the physical elution of olive oil through selected adsorbents.
Unveiling the Effects of Copper Ions in the Aggregation of Amyloidogenic Proteins
Authors: Oliveri Valentina
Published: September 2023

Amyloid diseases have become a global concern due to their increasing prevalence. Transition metals, including copper, can affect the aggregation of the pathological proteins involved in these diseases. Copper ions play vital roles in organisms, but the disruption of their homeostasis can negatively impact neuronal function and contribute to amyloid diseases with toxic protein aggregates, oxidative stress, mitochondrial dysfunction, impaired cellular signaling, inflammation, and cell death. Gaining insight into the imbalance of copper ions and its impact on protein folding and aggregation is crucial for developing focused therapies. This review examines the influence of copper ions on significant amyloid proteins/peptides, offering a comprehensive overview of the current understanding in this field.
Comparison of the Declared Nutrient Content of Plant-Based Meat Substitutes and Corresponding Meat Products and Sausages in Germany
Authors: Gréa Corinna , Dittmann Anna , Wolff David , Werner Romy , Turban Christin , Roser Silvia , Hoffmann Ingrid , Storcksdieck genannt Bonsmann Stefan
Published: September 2023

Plant-based meat substitutes (PBMS) are becoming increasingly popular due to growing concerns about health, animal welfare, and environmental issues associated with animal-based foods. The aim of this study was to compare the declared energy and nutrient contents of PBMS with corresponding meat products and sausages available on the German market. Mandatory nutrition labelling data of 424 PBMS and 1026 meat products and sausages, surveyed in 2021 and 2020, respectively, as part of the German national monitoring of packaged food were used to test for differences in energy and nutrient contents. Principal component analysis (PCA) was used to describe characteristics in the energy and nutrient contents. The comparison showed that most of the PBMS subcategories had significantly lower contents of fat and saturated fat but higher contents of carbohydrate and sugar than corresponding meat subcategories. For salt, the only striking difference was that PBMS salamis had lower salt content than meat salamis. Overall, the PCA revealed protein as a main characteristic for most PBMS categories, with the protein content being equivalent to or, in most protein-based PBMS, even higher than in the corresponding meat products. The wide nutrient content ranges within subcategories, especially for salt, reveal the need and potential for reformulation.
Soft Drinks and Symptoms of Depression and Anxiety in Overweight Subjects: A Longitudinal Analysis of an European Cohort
Authors: Castro Adoración , Gili Margalida , Visser Marjolein , Penninx Brenda W. J. H. , Brouwer Ingeborg A. , Montaño Juan José , Pérez-Ara María Ángeles , García-Toro Mauro , Watkins Ed , Owens Matt , Hegerl Ulrich , Kohls Elisabeth , Bot Mariska , Roca Miquel
Published: September 2023

Background: Studies about the association of carbonated/soft drinks, coffee, and tea with depression and anxiety are scarce and inconclusive and little is known about this association in European adults. Our aim was to examine the association between the consumption of these beverages and depressive and anxiety symptom severity. Methods: A total of 941 European overweight adults (mean age, 46.8 years) with subsyndromal depression that participated in the MooDFOOD depression prevention randomized controlled trial (Clinical Trials.gov identifier: NCT2529423; date of the study: from 2014 to 2018) were analyzed. Depressive and anxiety symptom severity and beverage consumption were assessed using multilevel mixed-effects ordinal logistic regression models for each beverage consumption (carbonated/soft drink with sugar, carbonated/soft drink with non-nutritive sweeteners, coffee, and tea) with the three repeated measures of follow-up (baseline and 6 and 12 months). A case report form for participants’ sociodemographic and clinical characteristics, the Food Frequency Questionnaire, the Patient Health Questionnaire-9, the Generalized Anxiety Disorder 7-Item Scale, the MINI International Neuropsychiatric Interview 5.0, the Short Questionnaire to Assess Health-Enhancing Psychical Activity, and the Alcohol Use Disorders Identification Test were the research tools used. Results: Daily consumption of carbonated/soft drinks with sugar was associated with a higher level of anxiety. Trends towards significance were found for associations between both daily consumption of carbonated/soft drinks with sugar and non-nutritive sweeteners and a higher level of depression. No relationship was found between coffee and tea consumption and the level of depression and anxiety. Conclusions: The high and regular consumption of carbonated/soft drink with sugar (amount of consumption: ≥1 unit (200 mL)/day) tended to be associated with higher level of anxiety in a multicountry sample of overweight subjects with subsyndromal depressive symptoms. It is important to point out that further research in this area is essential to provide valuable information about the intake patterns of non-alcoholic beverages and their relationship with affective disorders in the European adult population.
Liquorice Toxicity: A Comprehensive Narrative Review
Authors: Ceccuzzi Giovanna , Rapino Alessandro , Perna Benedetta , Costanzini Anna , Farinelli Andrea , Fiorica Ilaria , Marziani Beatrice , Cianci Antonella , Rossin Federica , Cesaro Alice Eleonora , Spampinato Michele Domenico , De Giorgio Roberto , Guarino Matteo
Published: September 2023

Background: Renowned since ancient times for its medical properties, liquorice is nowadays mainly used for flavoring candies or soft drinks. Continuous intake of large amounts of liquorice is a widely known cause of pseudo-hyperaldosteronism leading to hypertension and hypokalemia. These manifestations are usually mild, although in some cases may generate life-threatening complications, i.e., arrhythmias, muscle paralysis, rhabdomyolysis, and coma. In addition, liquorice has an important estrogenic-like activity. Methods: We summarized the current knowledge about liquorice and reviewed 104 case reports in both the English and Italian languages from inception to June 2023 concerning complications due to an excess of liquorice intake. Results: In contrast to most published data, female sex and old age do not appear to be risk factors. However, hypertension and electrolyte imbalance (mainly hypokalemia) are prevalent features. The detection of glycyrrhetinic acid in blood is very uncommon, and the diagnosis is essentially based on an accurate history taking. Conclusions: Although there is not a significant mortality rate, liquorice toxicity often requires hospitalization and therefore represents a significant health concern. Major pharmaceutical drug regulatory authorities should solicit public awareness about the potentially dangerous effects caused by excessive use of liquorice.
Effects of Low-Calorie Sweetener Restriction on Glycemic Variability and Cardiometabolic Health in Children with Type 1 Diabetes: Findings of a Pilot and Feasibility Study
Authors: Sylvetsky Allison C. , Moore Hailey R. , Zhu Xinyu , Kaidbey Jasmine H. , Kang Leyi , Saeed Abbas , Khattak Shazmeena , Grilo Mariana F. , Vallone Natalie , Kuttamperoor Janae , Cogen Fran R. , Elmi Angelo , Walter Peter J. , Cai Hongyi , DiPietro Loretta , Goran Michael I. , Streisand Randi
Published: September 2023

Low-calorie sweeteners (LCS) are commonly consumed by children with type 1 diabetes (T1D), yet their role in cardiometabolic health is unclear. This study examined the feasibility, acceptability, and preliminary effects of 12 weeks of LCS restriction among children with T1D. Children (n = 31) with T1D completed a two-week run-in (n = 28) and were randomly assigned to avoid LCS (LCS restriction, n = 15) or continue their usual LCS intake (n = 13). Feasibility was assessed using recruitment, retention, and adherence rates percentages. Acceptability was assessed through parents completing a qualitative interview (subset, n = 15) and a satisfaction survey at follow-up. Preliminary outcomes were between-group differences in change in average daily time-in-range (TIR) over 12 weeks (primary), and other measures of glycemic variability, lipids, inflammatory biomarkers, visceral adiposity, and dietary intake (secondary). Linear regression, unadjusted and adjusted for age, sex, race, and change in BMI, was used to compare mean changes in all outcomes between groups. LCS restriction was feasible and acceptable. No between-group differences in change in TIR or other measures of glycemic variability were observed. However, significant decreases in TNF-alpha (−0.23 ± 0.08 pg/mL) and improvements in cholesterol (−0.31 ± 0.18 mmol/L) and LDL (−0.60 ± 0.39 mmol/L) were observed with usual LCS intake, compared with LCS restriction. Those randomized to LCS restriction did not report increases in total or added sugar intake, and lower energy intake was reported in both groups (−190.8 ± 106.40 kcal LCS restriction, −245.3 ± 112.90 kcal usual LCS intake group). Decreases in percent energy from carbohydrates (−8.5 ± 2.61) and increases in percent energy from protein (3.2 ± 1.16) and fat (5.2 ± 2.02) were reported with usual LCS intake compared with LCS restriction. Twelve weeks of LCS restriction did not compromise glycemic variability or cardiometabolic outcomes in this small sample of youth with T1D. Further examination of LCS restriction among children with T1D is warranted.
Differences in Dietary Intake, Eating Occasion Timings and Eating Windows between Chronotypes in Adults Living with Type 2 Diabetes Mellitus
Authors: Katsarova Stanislava S. , Redman Emma , Arsenyadis Franciskos , Brady Emer M. , Rowlands Alex V. , Edwardson Charlotte L. , Goff Louise M. , Khunti Kamlesh , Yates Thomas , Hall Andrew P. , Davies Melanie J. , Henson Joseph
Published: September 2023

Chronotype studies investigating dietary intake, eating occasions (EO) and eating windows (EW) are sparse in people with type 2 Diabetes mellitus (T2DM). This analysis reports data from the CODEC study. The Morningness-Eveningness questionnaire (MEQ) assessed chronotype preference. Diet diaries assessed dietary intake and temporal distribution. Regression analysis assessed whether dietary intake, EW, or EO differed by chronotype. 411 participants were included in this analysis. There were no differences in energy, macronutrient intake or EW between chronotypes. Compared to evening chronotypes, morning and intermediate chronotypes consumed 36.8 (95% CI: 11.1, 62.5) and 20.9 (95% CI: −2.1, 44.1) fewer milligrams of caffeine per day, respectively. Evening chronotypes woke up over an hour and a half later than morning (01:36 95% CI: 01:09, 02:03) and over half an hour later than intermediate chronotypes (00:45 95% CI: 00:21; 01:09. Evening chronotypes went to sleep over an hour and a half later than morning (01:48 95% CI: 01:23; 02:13) and an hour later than intermediate chronotypes (01:07 95% CI: 00:45; 01:30). Evening chronotypes’ EOs and last caffeine intake occurred later but relative to their sleep timings. Future research should investigate the impact of chronotype and dietary temporal distribution on glucose control to optimise T2DM interventions.
Disruption of Vitamin D Signaling Impairs Adaptation of Cerebrocortical Microcirculation to Carotid Artery Occlusion in Hyperandrogenic Female Mice
Authors: Nagy Dorina , Hricisák László , Walford Guillaume Peter , Lékai Ágnes , Karácsony Gábor , Várbíró Szabolcs , Ungvári Zoltán , Benyó Zoltán , Pál Éva
Published: September 2023

Vitamin D deficiency contributes to the pathogenesis of age-related cerebrovascular diseases, including ischemic stroke. Sex hormonal status may also influence the prevalence of these disorders, indicated by a heightened vulnerability among postmenopausal and hyperandrogenic women. To investigate the potential interaction between sex steroids and disrupted vitamin D signaling in the cerebral microcirculation, we examined the cerebrovascular adaptation to unilateral carotid artery occlusion (CAO) in intact, ovariectomized, and hyperandrogenic female mice with normal or functionally inactive vitamin D receptor (VDR). We also analyzed the morphology of leptomeningeal anastomoses, which play a significant role in the compensation. Ablation of VDR by itself did not impact the cerebrocortical adaptation to CAO despite the reduced number of pial collaterals. While ovariectomy did not undermine compensatory mechanisms following CAO, androgen excess combined with VDR inactivity resulted in prolonged hypoperfusion in the cerebral cortex ipsilateral to the occlusion. These findings suggest that the cerebrovascular consequences of disrupted VDR signaling are less pronounced in females, providing a level of protection even after ovariectomy. Conversely, even short-term androgen excess with lacking VDR signaling may lead to unfavorable outcomes of ischemic stroke, highlighting the complex interplay between sex steroids and vitamin D in terms of cerebrovascular diseases.
Comparisons of Different Carbohydrate Quality Indices for Risk of Type 2 Diabetes in the Malmö Diet and Cancer Study
Authors: Ramstedt Michaela , Janzi Suzanne , Olsson Kjell , González-Padilla Esther , Ramne Stina , Borné Yan , Ericson Ulrika , Sonestedt Emily
Published: September 2023

Carbohydrate quality might be more important than quantity to reduce type 2 diabetes (T2D) risk. Various metrics of carbohydrate quality exist; however, their associations with T2D have only been studied to a limited extent. Consequently, the aim was to investigate the association between four different pre-defined carbohydrate quality indices, with various amounts of fiber (≥1 g) and free sugar (<1 or <2 g) per 10 g of carbohydrates, and T2D risk among 26,622 individuals without diabetes from the Malmö Diet and Cancer cohort. Dietary data were collected through a food diary, diet frequency questionnaire, and interview. After a mean follow-up of 18 years, 4046 cases were identified through registers. After adjusting for potential confounders, no statistically significant associations were found for any of the indices. When excluding individuals with past dietary changes and potential misreporting of energy (36% of the population), lower risk was found for the following intake ratios: 10:1:2 carbohydrate:fiber:free sugar (HR = 0.82; 95% CI = 0.70–0.97), and 10:1&1:2 carbohydrate:fiber and fiber:free sugar, respectively (HR = 0.84; 95% CI = 0.72–0.97). Our findings indicate that adherence to a diet with high amounts of fiber and moderate amounts of free sugar in relation to total carbohydrate intake may be associated with a lower risk of T2D.
Selective Androgen Receptor Modulators Combined with Treadmill Exercise Have No Bone Benefit in Healthy Adult Rats
Authors: Komrakova Marina , Schilling Arndt Friedrich , Lehmann Wolfgang , Vasilev Veselin , Georgieva Katerina , Gerginska Fanka , Boyadjiev Nikolay , Delchev Slavi
Published: September 2023

The effects of combination treatments using the selective androgen receptor modulators (SARMs) ostarine (OST) or ligandrol (LIG) with treadmill exercise (TE) were studied in healthy adult rats. Fifteen-week-old male Wistar rats were divided into groups (n = 10/group). Experiment 1 consisted of (1) Control group: sedentary rats receiving vehicle; (2) OST: sedentary rats receiving OST; (3) TE: training rats receiving vehicle; (4) OST + TE: training rats receiving OST. Experiment 2 consisted of (1) LIG: sedentary group receiving LIG; (2) LIG + TE: training group receiving LIG. The TE regime was as follows: 25 m/min, 5° elevation, 40 min, five times/week, and the sedentary regime was 5 min, three times/week. OST and LIG were administered subcutaneously (0.4 mg/kg body weight/day, five times/week). After eight weeks, bone samples underwent microcomputed tomographical, biomechanical, histological, and ashing analyses. All the treatments had weak effects on the bone structure without affecting bone biomechanics. The OST + TE improved bone structure, while the LIG + TE had unfavorable effects. In serum, OST, OST + TE, and LIG + TE altered cholesterol and lipoprotein levels; TE did not change the serum parameters. The SARM treatments had no clear bone benefit, and the serum effects can be considered as side effects. TE represents a safe treatment. Because SARMs are increasingly applied in gyms along with physical activities, attention should be paid to possible side effects.
Molecular Dynamics Simulations of Drug-Conjugated Cell-Penetrating Peptides
Authors: Ivánczi Márton , Balogh Balázs , Kis Loretta , Mándity István
Published: September 2023

Cell-penetrating peptides (CPPs) are small peptides capable of translocating through biological membranes carrying various attached cargo into cells and even into the nucleus. They may also participate in transcellular transport. Our in silico study intends to model several peptides and their conjugates. We have selected three CPPs with a linear backbone, including penetratin, a naturally occurring oligopeptide; two of its modified sequence analogues (6,14-Phe-penetratin and dodeca-penetratin); and three natural CPPs with a cyclic backbone: Kalata B1, the Sunflower trypsin inhibitor 1 (SFT1), and Momordica cochinchinensis trypsin inhibitor II (MCoTI-II). We have also built conjugates with the small-molecule drug compounds doxorubicin, zidovudine, and rasagiline for each peptide. Molecular dynamics (MD) simulations were carried out with explicit membrane models. The analysis of the trajectories showed that the interaction of penetratin with the membrane led to spectacular rearrangements in the secondary structure of the peptide, while cyclic peptides remained unchanged due to their high conformational stability. Membrane–peptide and membrane–conjugate interactions have been identified and compared. Taking into account well-known examples from the literature, our simulations demonstrated the utility of computational methods for CPP complexes, and they may contribute to a better understanding of the mechanism of penetration, which could serve as the basis for delivering conjugated drug molecules to their intracellular targets.
Evaluation of Two Osmosis-Based Methods for the Preparation of Drug Delivery Systems Based on Red Blood Cells
Authors: Gutierrez-Millan Carmen , Barez Diaz Celia , Alvarez Vizan Lydia , Colino Clara I.
Published: September 2023

Erythrocytes have been thoroughly investigated as drug delivery systems for a wide range of therapeutic molecules and using different kinds of loading methods, outstanding the osmosis-based methods as the most used ones. Most of them involve too much handling of blood components and the immediate obtention of fresh blood. Based on our group’s considerable experience in dialysis-based carrier erythrocyte preparation, this study details a simple method based on hypotonic dilution and subsequent resealing that has been developed for stavudine using packed erythrocytes from a local blood bank. Properties of the obtained carrier erythrocytes were studied in comparison to those prepared by dialysis. Erythrocytes’ morphology, osmotic fragility, hematological parameters, and in vitro release profiles were evaluated. Loaded erythrocytes obtained with the proposed method did not show impaired properties in comparison with those obtained with our reference method, provided that the buffer composition remained the same. In the present work, we have optimized a simplified method for erythrocytes’ drug loading, which can use blood transfusion products and could be easily automatized and scalable.
Elucidating Berberine’s Therapeutic and Photosensitizer Potential through Nanomedicine Tools
Authors: Marques Célia , Fernandes Maria Helena , Lima Sofia A. Costa
Published: September 2023

Berberine, an isoquinoline alkaloid extracted from plants of the Berberidaceae family, has been gaining interest due to anti-inflammatory and antioxidant activities, as well as neuro and cardiovascular protective effects in animal models. Recently, photodynamic therapy demonstrated successful application in many fields of medicine. This innovative, non-invasive treatment modality requires a photosensitizer, light, and oxygen. In particular, the photosensitizer can selectively accumulate in diseased tissues without damaging healthy cells. Berberine’s physicochemical properties allow its use as a photosensitising agent for photodynamic therapy, enabling reactive oxygen species production and thus potentiating treatment efficacy. However, berberine exhibits poor aqueous solubility, low oral bioavailability, poor cellular permeability, and poor gastrointestinal absorption that hamper its therapeutic and photodynamic efficacy. Nanotechnology has been used to minimize berberine’s limitations with the design of drug delivery systems. Different nanoparticulate delivery systems for berberine have been used, as lipid-, inorganic- and polymeric-based nanoparticles. These berberine nanocarriers improve its therapeutic properties and photodynamic potential. More specifically, they extend its half-life, increase solubility, and allow a high permeation and targeted delivery. This review describes different nano strategies designed for berberine delivery as well as berberine’s potential as a photosensitizer for photodynamic therapy. To benefit from berberine’s overall potential, nanotechnology has been applied for berberine-mediated photodynamic therapy.