bluuebunny/crossref_metadata_2025 huggingface dataset:
Endurance Swimming Is Related to Summer Lake Survival of Rainbow Trout in a Warm Lake with Avian Piscivores
Authors: Verhille Christine E. , Farrell Anthony P.
Published: April 2023

Fitness of fish is assumed to be influenced by locomotion performance, but empirical evidence linking swimming capacity to survival in nature remains sparse. Poor triploid (3N) fish aerobic swimming performance in conjunction with production of sibling diploid (2N) and 3N populations of genetically identical origin to minimize variability among compared populations make 3N trout an informative system to test hypotheses about fitness consequences of fish locomotion. Here, we ask if reduced survival of 3N relative to 2N trout in natural ecosystems during periods of high temperature relate to a lower aerobic swimming capacity and aerobic scope of 3N compared with 2N conspecifics. Three-yearly cohorts of conspecific 2N and 3N hatchery-reared, yearling rainbow trout were ranked for swimming endurance, externally marked for their endurance quantile, and then stocked into two lakes as yearlings to quantify their survival in the wild over summer as a function of ploidy, temperature and endurance; all while tracking temperature and depth habitat utilization via telemetry. As expected, 3N swimming endurance was lower than that of 2N, but with considerable individual overlap. Aerobic swimming endurance, especially for 3N, was predictive of summer survival in a warm lake where piscivorous birds potentially exerted high predation pressure, resulting in low fish survival. This empirical evidence of a connection between swimming endurance and fitness provides support for long held assumptions of this relationship and could inform future sport fishing stocking industry practices to match fish strains to ideal habitats.
FEDformer-Based Paddy Quality Assessment Model Affected by Toxin Change in Different Storage Environments
Authors: Li Zihan , Zhang Qingchuan , Dong Wei , Liu Yingjie , Wei Siwei , Zuo Min
Published: April 2023

The storage environment can significantly impact paddy quality, which is vital to human health. Changes in storage can cause growth of fungi that affects grain quality. This study analyzed grain storage monitoring data from over 20 regions and found that five factors are essential in predicting quality changes during storage. The study combined these factors with the FEDformer (Frequency Enhanced Decomposed Transformer for Long-term Series Forecasting) model and k-medoids algorithm to construct a paddy quality change prediction model and a grading evaluation model, which showed the highest accuracy and lowest error in predicting quality changes during paddy storage. The results emphasize the need for monitoring and controlling the storage environment to preserve grain quality and ensure food safety.
On Coupled System of Langevin Fractional Problems with Different Orders of μ-Caputo Fractional Derivatives
Authors: Almaghamsi Lamya , Alruwaily Ymnah , Karthikeyan Kulandhaivel , El-hady El-sayed
Published: April 2023

In this paper, we study coupled nonlinear Langevin fractional problems with different orders of μ-Caputo fractional derivatives on arbitrary domains with nonlocal integral boundary conditions. In order to ensure the existence and uniqueness of the solutions to the problem at hand, the tools of the fixed-point theory are applied. An overview of the main results of this study is presented through examples.
Efficient Degradation for Raffinose and Stachyose of a β-D-Fructofuranosidase and Its New Function to Improve Gel Properties of Coagulated Fermented-Soymilk
Authors: Chen Zhou , Shen Yimei , Xu Jiangqi
Published: April 2023

A novel β-D-fructofuranosidase gene was identified via database mining from Leptothrix cholodnii. The gene was chemically synthesized and expressed in Escherichia coli, resulting in the production of a highly efficient enzyme known as LcFFase1s. The enzyme exhibited optimal activity at pH 6.5 and a temperature of 50 °C while maintaining stability at pH 5.5–8.0 and a temperature below 50 °C. Furthermore, LcFFase1s exhibited remarkable resistance to commercial proteases and various metal ions that could interfere with its activity. This study also revealed a new hydrolysis function of LcFFase1s, which could completely hydrolyze 2% raffinose and stachyose within 8 h and 24 h, respectively, effectively reducing the flatulence factor in legumes. This discovery expands the potential applications of LcFFase1s. Additionally, the incorporation of LcFFase1s significantly reduced the particle size of coagulated fermented-soymilk gel, resulting in a smoother texture while maintaining the gel hardness and viscosity formed during fermentation. This represents the first report of β-D-fructofuranosidase enhancing coagulated fermented-soymilk gel properties, highlighting promising possibilities for future applications of LcFFase1s. Overall, the exceptional enzymatic properties and unique functions of LcFFase1s render it a valuable tool for numerous applications.
Young Onset Alzheimer’s Disease Associated with C9ORF72 Hexanucleotide Expansion: Further Evidence for a Still Unsolved Association
Authors: Vinceti Giulia , Gallingani Chiara , Zucchi Elisabetta , Martinelli Ilaria , Gianferrari Giulia , Simonini Cecilia , Bedin Roberta , Chiari Annalisa , Zamboni Giovanna , Mandrioli Jessica
Published: April 2023

Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are recognized as part of a disease continuum (FTD-ALS spectrum), in which the most common genetic cause is chromosome 9 open reading frame 72 (C9ORF72) gene hexanucleotide repeat expansion. The clinical phenotype of patients carrying this expansion varies widely and includes diseases beyond the FTD-ALS spectrum. Although a few cases of patients with C9ORF72 expansion and a clinical or biomarker-supported diagnosis of Alzheimer’s disease (AD) have been described, they have been considered too sparse to establish a definite association between the C9ORF72 expansion and AD pathology. Here, we describe a C9ORF72 family with pleomorphic phenotypical expressions: a 54-year-old woman showing cognitive impairment and behavioral disturbances with both neuroimaging and cerebrospinal fluid (CSF) biomarkers consistent with AD pathology, her 49-year-old brother with typical FTD-ALS, and their 63-year-old mother with the behavioral variant of FTD and CSF biomarkers suggestive of AD pathology. The young onset of disease in all three family members and their different phenotypes and biomarker profiles make the simple co-occurrence of different diseases an extremely unlikely explanation. Our report adds to previous findings and may contribute to further expanding the spectrum of diseases associated with C9ORF72 expansion.
The Hexosamine Biosynthesis Pathway: Regulation and Function
Authors: Paneque Alysta , Fortus Harvey , Zheng Julia , Werlen Guy , Jacinto Estela
Published: April 2023

The hexosamine biosynthesis pathway (HBP) produces uridine diphosphate-N-acetyl glucosamine, UDP-GlcNAc, which is a key metabolite that is used for N- or O-linked glycosylation, a co- or post-translational modification, respectively, that modulates protein activity and expression. The production of hexosamines can occur via de novo or salvage mechanisms that are catalyzed by metabolic enzymes. Nutrients including glutamine, glucose, acetyl-CoA, and UTP are utilized by the HBP. Together with availability of these nutrients, signaling molecules that respond to environmental signals, such as mTOR, AMPK, and stress-regulated transcription factors, modulate the HBP. This review discusses the regulation of GFAT, the key enzyme of the de novo HBP, as well as other metabolic enzymes that catalyze the reactions to produce UDP-GlcNAc. We also examine the contribution of the salvage mechanisms in the HBP and how dietary supplementation of the salvage metabolites glucosamine and N-acetylglucosamine could reprogram metabolism and have therapeutic potential. We elaborate on how UDP-GlcNAc is utilized for N-glycosylation of membrane and secretory proteins and how the HBP is reprogrammed during nutrient fluctuations to maintain proteostasis. We also consider how O-GlcNAcylation is coupled to nutrient availability and how this modification modulates cell signaling. We summarize how deregulation of protein N-glycosylation and O-GlcNAcylation can lead to diseases including cancer, diabetes, immunodeficiencies, and congenital disorders of glycosylation. We review the current pharmacological strategies to inhibit GFAT and other enzymes involved in the HBP or glycosylation and how engineered prodrugs could have better therapeutic efficacy for the treatment of diseases related to HBP deregulation.
Content and Face Validity of the Evaluation Tool of Health Information for Consumers (ETHIC): Getting Health Information Accessible to Patients and Citizens
Authors: Cocchi Simone , Cipolat Mis Chiara , Mazzocut Mauro , Barbieri Irene , Bassi Maria Chiara , Cavuto Silvio , Di Leo Silvia , Miraglia Raineri Alessandra , Cafaro Valentina ,   ETHIC Validation Group
Published: April 2023

Background: Health information concerns both individuals’ engagement and the way services and professionals provide information to facilitate consumers’ health decision making. Citizens’ and patients’ participation in the management of their own health is related to the availability of tools making health information accessible, thus promoting empowerment and making care more inclusive and fairer. A novel instrument was developed (Evaluation Tool of Health Information for Consumers—ETHIC) for assessing the formal quality of health information materials written in Italian language. This study reports ETHIC’s content and face validity. Methods: A convenience sample of 11 experts and 5 potential users was involved. The former were requested to evaluate relevance and exhaustiveness, the latter both readability and understandability of ETHIC. The Content Validity Index (CVI) was calculated for ETHIC’s sections and items; experts and potential users’ feedback were analyzed by the authors. Results: All sections and most items were evaluated as relevant. A new item was introduced. Potential users provided the researchers with comments that partly confirmed ETHIC’s clarity and understandability. Conclusions: Our findings strongly support the relevance of ETHIC’s sections and items. An updated version of the instrument matching exhaustivity, readability, and understandability criteria was obtained, which will be assessed for further steps of the validation process.
Association between Diet and Adiposity in Adults: Influence of Sedentary Behavior Patterns
Authors: Beretta Victor Spiandor , Tebar William Rodrigues , Scarabottolo Catarina Covolo , Delfino Leandro Dragueta , Saraiva Bruna Thamyres Ciccotti , Santos Amanda Barbosa , Antunes Ewerton Pegorelli , Leoci Isabella Cristina , Ferrari Gerson , Christofaro Diego Giulliano Destro
Published: April 2023

This study analyzed the influence of sedentary behavior (SB) on the association between dietary patterns and adiposity in community-dwelling adults. Eight hundred and forty-three adults (age: 56.5 ± 18.3 years) participated in this cross-sectional epidemiological study. Dietary patterns were evaluated using self-report questions regarding the weekly frequency of consumption of certain foods. Adiposity was determined using anthropometric measurements of weight, waist circumference, and height. SB was evaluated according to the time spent on screen devices. The usual physical activity level and socioeconomic status were considered confounding factors. Associations were determined using multivariate linear models with simultaneous adjustments for confounding variables. A statistical analysis indicated that fruit consumption was negatively related to the body mass index, regardless of the adjustment for SB domains. Red meat consumption was positively related to the body mass index, and fried food consumption was positively related to the waist-to-height ratio, regardless of the adjustment for SB domains. The consumption of fried food was positively associated with global and central adiposity after the adjustments for confounding factors and time spent on screen devices. We concluded that dietary habits are related to adiposity in adults. However, SB domains seem to influence the relationship between body adiposity and dietary habits, mainly regarding the consumption of fried foods.
Validation of Generalized Anxiety Disorder 6 (GAD-6)—A Modified Structure of Screening for Anxiety in the Adolescent French Population
Authors: Todorović Anja , Baumann Cédric , Blanchin Myriam , Bourion-Bédès Stéphanie
Published: April 2023

Anxiety disorders remain underdiagnosed and undertreated, especially in child and adolescent populations. This study aimed to examine the construct validity of the Generalized Anxiety Disorder Scale 7 (GAD-7) in a sample of French adolescents by combining the Classical Test Theory (CTT) and the Item Response Theory (IRT) and to assess the invariance of items. A total of 284 adolescents enrolled in school in the Lorraine region were randomly selected to participate in a cross-sectional study. A psychometric evaluation was performed using a combination of CTT and IRT analyses. The study of psychometric properties of GAD-7 revealed poor adequation to the sample population, and engendered the deletion of one item (#7) and the merger of two response modalities (#2 and #3). These modifications generated the new GAD-6 scale, which had a good internal consistency reliability (Cronbach α = 0.85; PSI = 0.83), acceptable goodness-of-fit indices (χ2 = 28.89, df = 9, P = 0.001; RMSEA (90% CI) = 0.088 [0.054; 0.125]; SRMR = 0.063; CFI = 0.857), and an acceptable convergent validity (r = –0.62). Only one item (#5) had a consistent Differential Item Functioning (DIF) by gender. This study evaluated the structure of the GAD-7 scale, which was essentially intended at discriminating adolescent patients with high levels of anxiety, and adapted it to a population of adolescents from the general population. The GAD-6 scale presents better psychometric properties in this general population than the original GAD-7 version.
Fatigue on Waking, Insomnia, and Workplace Relationship Problems May Help to Detect Suicidal Ideation among New Middle-Aged Primary Care Patients: A 6-Month Prospective Study in Japan
Authors: Fujieda Megumi , Uchida Katsuhisa , Ikebe Shinichiro , Kimura Akihiro , Kimura Masashi , Watanabe Toshiaki , Sakamoto Hisako , Matsumoto Teruaki , Uchimura Naohisa
Published: April 2023

Signs of suicidal depression often go undetected in primary care settings. This study explored predictive factors for depression with suicidal ideation (DSI) among middle-aged primary care patients at 6 months after an initial clinic visit. New patients aged 35–64 years were recruited from internal medicine clinics in Japan. Baseline characteristics were elicited using self-administered and physician questionnaires. DSI was evaluated using the Zung Self-Rating Depression Scale and the Profile of Mood States at enrollment and 6 months later. Multiple logistic regression analysis was conducted to calculate adjusted odds ratios for DSI. Sensitivity, specificity, and likelihood ratios for associated factors were calculated. Among 387 patients, 13 (3.4%) were assessed as having DSI at 6 months. Adjusted for sex, age, and related factors, significant odds ratios for DSI were observed for “fatigue on waking ≥1/month” (7.90, 95% confidence intervals: 1.06–58.7), “fatigue on waking ≥1/week” (6.79, 1.02–45.1), “poor sleep status” (8.19, 1.05–63.8), and “relationship problems in the workplace” (4.24, 1.00–17.9). Fatigue on waking, sleep status, and workplace relationship problems may help predict DSI in primary care. Because the sample size in this investigation was small, further studies with larger samples are needed to confirm our findings.
The Roles of Carbon Trading System and Sustainable Energy Strategies in Reducing Carbon Emissions—An Empirical Study in China with Panel Data
Authors: Yu Yue , Xu Yishuang
Published: April 2023

Carbon emission reduction is now a vital element in urban development. This study explores the effectiveness of the two emerging methods to reduce carbon emission, which are carbon emissions trading system (ETS) and sustainable energy strategy, in the process of urbanization. We review the policy in the past decades to demonstrate the development of these two streams of carbon emission reduction methods and empirically test the effectiveness of the two methods with panel data across 30 provinces in China from 2009 to 2019. The sustainable energy strategy is confirmed to be effective in reducing carbon emissions in the region, while the effectiveness of carbon emissions trading system varies. We find that (1) substituting fossil fuel with other sustainable energy resources can effectively reduce the carbon emission; (2) the rewards from carbon emissions trading is a good incentive for the enterprises to reduce the carbon emissions; however, it is more tempting in the provinces that have the carbon emissions trading system, although the trading can be conducted across the province boarder. Our findings indicate that the sustainable energy strategy is a good practice and worth expanding to the whole country. It can be difficult for some provinces to transform and adopt the sustainable energy strategy if the fossil fuel is the major source for economic production. It is important to avoid setting fossil fuel as the main source for economic production or household consumption in the urbanization process. Meanwhile the carbon emissions trading system is found to contribute to CO2 emissions reduction only within the province. Therefore, having more provinces piloting the ETS will help the CO2 emission reduction further.
Multi-City Analysis of the Acute Effect of Polish Smog on Cause-Specific Mortality (EP-PARTICLES Study)
Authors: Święczkowski Michał , Dobrzycki Sławomir , Kuźma Łukasz
Published: April 2023

Polish smog is a specific type of air pollution present in Eastern Poland, which may cause particularly adverse cardiovascular effects. It is characterized primarily by high concentrations of particulate matter (PM) and different favorable conditions of formation. Our study aimed to assess whether PM and nitrogen dioxide (NO2) have a short-term impact on mortality due to acute coronary syndrome (ACS) and ischemic stroke (IS). The study covered the years 2016–2020, a total of 6 million person-years from five main cities in Eastern Poland. To evaluate the association between air pollution and cause-specific mortality, a case-crossover study design with conditional logistic regression was used at days with LAG from 0 to 2. We recorded 87,990 all-cause deaths, including 9688 and 3776 deaths due to ACS and IS, respectively. A 10 μg/m3 increase in air pollutants was associated with an increase in mortality due to ACS (PM2.5 OR = 1.029, 95%CI 1.011–1.047, p = 0.002; PM10 OR = 1.015, 95%CI 1–1.029, p = 0.049) on LAG 0. On LAG 1 we recorded an increase in both IS (PM2.5 OR = 1.03, 95%CI 1.001–1.058, p = 0.04) and ACS (PM2.5 OR = 1.028, 95%CI 1.01–1.047, p = 0.003; PM10 OR = 1.026, 95%CI 1.011–1.041, p = 0.001; NO2 OR = 1.036, 95%CI 1.003–1.07, p = 0.04). There was a strong association between air pollution and cause-specific mortality in women (ACS: PM2.5 OR = 1.032, 95%CI 1.006–1.058, p = 0.01; PM10 OR = 1.028, 95%CI 1.008–1.05, p = 0.01) and elderly (ACS: PM2.5 OR = 1.03, 95%CI 1.01–1.05, p = 0.003; PM10 OR = 1.027, 95% CI 1.011–1.043, p < 0.001 and IS: PM2.5 OR = 1.037, 95%CI 1.007–1.069, p = 0.01; PM10 OR = 1.025, 95%CI 1.001–1.05, p = 0.04). The negative influence of PMs was observed on mortality due to ACS and IS. NO2 was associated with only ACS-related mortality. The most vulnerable subgroups were women and the elderly.
Potential Benefits of Dietary Plant Compounds on Normal and Tumor Brain Cells in Humans: In Silico and In Vitro Approaches
Authors: Pirvu Lucia Camelia , Neagu Georgeta , Albulescu Adrian , Stefaniu Amalia , Pintilie Lucia
Published: April 2023

Neuroblastoma can be accessed with compounds of larger sizes and wider polarities, which do not usually cross the blood–brain barrier. Clinical data indicate cases of spontaneous regression of neuroblastoma, suggesting a reversible point in the course of cell brain tumorigenesis. Dual specificity tyrosine-phosphorylation-regulated kinase2 (DYRK2) is a major molecular target in tumorigenesis, while curcumin was revealed to be a strong inhibitor of DYRK2 (PBD ID: 5ZTN). Methods: in silico studies by CLC Drug Discovery Workbench (CLC) and Molegro Virtual Docker (MVD) Software on 20 vegetal compounds from the human diet tested on 5ZTN against the native ligand curcumin, in comparison with anemonin. In vitro studies were conducted on two ethanolic extracts from Anemone nemorosa tested on normal and tumor human brain cell lines NHA and U87, compared with four phenolic acids (caffeic, ferulic, gentisic, and para-aminobenzoic/PABA). Conclusions: in silico studies revealed five dietary compounds (verbascoside, lariciresinol, pinoresinol, medioresinol, matairesinol) acting as stronger inhibitors of 5ZTN compared to the native ligand curcumin. In vitro studies indicated that caffeic acid has certain anti-proliferative effects on U87 and small benefits on NHA viability. A. nemorosa extracts indicated potential benefits on NHA viability, and likely dangerous effects on U87.
Autophagy in Spinocerebellar Ataxia Type 3: From Pathogenesis to Therapeutics
Authors: Paulino Rodrigo , Nóbrega Clévio
Published: April 2023

Machado–Joseph disease (MJD) or spinocerebellar ataxia 3 (SCA3) is a rare, inherited, monogenic, neurodegenerative disease, and the most common SCA worldwide. MJD/SCA3 causative mutation is an abnormal expansion of the triplet CAG at exon 10 within the ATXN3 gene. The gene encodes for ataxin-3, which is a deubiquitinating protein that is also involved in transcriptional regulation. In normal conditions, the ataxin-3 protein polyglutamine stretch has between 13 and 49 glutamines. However, in MJD/SCA3 patients, the size of the stretch increases from 55 to 87, contributing to abnormal protein conformation, insolubility, and aggregation. The formation of aggregates, which is a hallmark of MJD/SCA3, compromises different cell pathways, leading to an impairment of cell clearance mechanisms, such as autophagy. MJD/SCA3 patients display several signals and symptoms in which the most prominent is ataxia. Neuropathologically, the regions most affected are the cerebellum and the pons. Currently, there are no disease-modifying therapies, and patients rely only on supportive and symptomatic treatments. Due to these facts, there is a huge research effort to develop therapeutic strategies for this incurable disease. This review aims to bring together current state-of-the-art strategies regarding the autophagy pathway in MJD/SCA3, focusing on evidence for its impairment in the disease context and, importantly, its targeting for the development of pharmacological and gene-based therapies.
Neural Isoforms of Agrin Are Generated by Reduced PTBP1−RNA Interaction Network Spanning the Neuron−Specific Splicing Regions in AGRN
Authors: Bushra Samira , Lin Ying-Ni , Joudaki Atefeh , Ito Mikako , Ohkawara Bisei , Ohno Kinji , Masuda Akio
Published: April 2023

Agrin is a heparan sulfate proteoglycan essential for the clustering of acetylcholine receptors at the neuromuscular junction. Neuron−specific isoforms of agrin are generated by alternative inclusion of three exons, called Y, Z8, and Z11 exons, although their processing mechanisms remain elusive. We found, by inspection of splicing cis−elements into the human AGRN gene, that binding sites for polypyrimidine tract binding protein 1 (PTBP1) were extensively enriched around Y and Z exons. PTBP1−silencing enhanced the coordinated inclusion of Y and Z exons in human SH−SY5Y neuronal cells, even though three constitutive exons are flanked by these alternative exons. Deletion analysis using minigenes identified five PTBP1−binding sites with remarkable splicing repression activities around Y and Z exons. Furthermore, artificial tethering experiments indicated that binding of a single PTBP1 molecule to any of these sites represses nearby Y or Z exons as well as the other distal exons. The RRM4 domain of PTBP1, which is required for looping out a target RNA segment, was likely to play a crucial role in the repression. Neuronal differentiation downregulates PTBP1 expression and promotes the coordinated inclusion of Y and Z exons. We propose that the reduction in the PTPB1−RNA network spanning these alternative exons is essential for the generation of the neuron−specific agrin isoforms.
Development of an Inflammation-Triggered In Vitro “Leaky Gut” Model Using Caco-2/HT29-MTX-E12 Combined with Macrophage-like THP-1 Cells or Primary Human-Derived Macrophages
Authors: Le Nguyen Phan Khoi , Altenburger Markus Jörg , Lamy Evelyn
Published: April 2023

The “leaky gut” syndrome describes a damaged (leaky) intestinal mucosa and is considered a serious contributor to numerous chronic diseases. Chronic inflammatory bowel diseases (IBD) are particularly associated with the “leaky gut” syndrome, but also allergies, autoimmune diseases or neurological disorders. We developed a complex in vitro inflammation-triggered triple-culture model using 21-day-differentiated human intestinal Caco-2 epithelial cells and HT29-MTX-E12 mucus-producing goblet cells (90:10 ratio) in close contact with differentiated human macrophage-like THP-1 cells or primary monocyte-derived macrophages from human peripheral blood. Upon an inflammatory stimulus, the characteristics of a “leaky gut” became evident: a significant loss of intestinal cell integrity in terms of decreased transepithelial/transendothelial electrical resistance (TEER), as well as a loss of tight junction proteins. The cell permeability for FITC-dextran 4 kDa was then increased, and key pro-inflammatory cytokines, including TNF-alpha and IL-6, were substantially released. Whereas in the M1 macrophage-like THP-1 co-culture model, we could not detect the release of IL-23, which plays a crucial regulatory role in IBD, this cytokine was clearly detected when using primary human M1 macrophages instead. In conclusion, we provide an advanced human in vitro model that could be useful for screening and evaluating therapeutic drugs for IBD treatment, including potential IL-23 inhibitors.
In Vivo Inflammation Caused by Achromobacter spp. Cystic Fibrosis Clinical Isolates Exhibiting Different Pathogenic Characteristics
Authors: Sandri Angela , Saitta Giulia Maria , Veschetti Laura , Boschi Federico , Passarelli Mantovani Rebeca , Carelli Maria , Melotti Paola , Signoretto Caterina , Boaretti Marzia , Malerba Giovanni , Lleò Maria M.
Published: April 2023

Achromobacter spp. lung infection in cystic fibrosis has been associated with inflammation, increased frequency of exacerbations, and decline of respiratory function. We aimed to evaluate in vivo the inflammatory effects of clinical isolates exhibiting different pathogenic characteristics. Eight clinical isolates were selected based on different pathogenic characteristics previously assessed: virulence in Galleria mellonella larvae, cytotoxicity in human bronchial epithelial cells, and biofilm formation. Acute lung infection was established by intratracheal instillation with 10.5 × 108 bacterial cells in wild-type and CFTR-knockout (KO) mice expressing a luciferase gene under control of interleukin-8 promoter. Lung inflammation was monitored by in vivo bioluminescence imaging up to 48 h after infection, and mortality was recorded up to 96 h. Lung bacterial load was evaluated by CFU count. Virulent isolates caused higher lung inflammation and mice mortality, especially in KO animals. Isolates both virulent and cytotoxic showed higher persistence in mice lungs, while biofilm formation was not associated with lung inflammation, mice mortality, or bacterial persistence. A positive correlation between virulence and lung inflammation was observed. These results indicate that Achromobacter spp. pathogenic characteristics such as virulence and cytotoxicity may be associated with clinically relevant effects and highlight the importance of elucidating their mechanisms.
Intelligent Augmented Reality for Learning Geometry
Authors: Uriarte-Portillo Aldo , Zatarain-Cabada Ramón , Barrón-Estrada María Lucía , Ibáñez María Blanca , González-Barrón Lucía-Margarita
Published: April 2023

This work describes a learning tool named ARGeoITS that combines augmented reality with an intelligent tutoring system to support geometry learning. The work depicts a study developed in Mexico to measure the impact on the learning and motivation of students using two different learning systems: an intelligent tutoring system with augmented reality (ARGeoITS) and a system with only augmented reality (ARGeo). To study the effect of this type of technology (ARGeoITS, ARGeo) and time of assessment (pre-, post-) on learning gains and motivation, we applied a 2 × 2 factorial design to 106 middle school students. Both pretest and post-test questionnaires were applied to each group to determine the students’ learning gains, as was an IMMS motivational survey to evaluate the students’ motivation. The results show that: (1) students who used the intelligent tutoring system ARGeoITS scored higher in learning gain (7.47) compared with those who used ARGeo (6.83); and (2) both the ARGeoITS and ARGeo learning tools have a positive impact on students’ motivation. The research findings imply that intelligent tutoring systems that integrate augmented reality can be exploited as an effective learning environment to help middle–high school students learn difficult topics such as geometry.
Mild and Fast Construction of Ni-Based Electrodes for Industrial-Grade Water Splitting
Authors: Lu Zikang , Liang Rikai , Shao Yuqi , Hao Weiju
Published: April 2023

Achieving high−efficiency and stable hydrogen evolution from water splitting is a great challenge. Herein, a facilely prepared two−dimenssional self−supported catalytic electrode with excellent stability is constructed for large−scale hydrogen production from alkaline simulated seawater. The bifunctional catalytic electrode is prepared by a fast and mild one−step of sodium borohydride etching on a nickel foam (NF) substrate without adding other additives (NF@NiBx−3h). The overpotential of the hydrogen/oxygen evolution reaction (HER/OER) in alkaline−simulated seawater at 10 mA cm−2 is 96 mV and 261 mV. At 200 mA cm−2, the NF@NiBx−3h electrode shows good stability over 7 days throughout the water splitting process due to the corrosion resistance of the NF substrate, and strong adhesion between the Ni−B active material and the substrate. This work demonstrates a novel strategy for fabricating catalytic electrodes with high−performance, low cost and excellent stability.
Cimicids of Medical and Veterinary Importance
Authors: Hamlili Fatima , Bérenger Jean , Parola Philippe
Published: April 2023

Members of the Cimicidae family are significant pests for mammals and birds, and they have attracted medical and veterinary interest. A number of recent studies have investigated bed bugs, due to their dramatic resurgence all over the world. Indeed, bed bugs are of significant public health and socioeconomic importance since they lead to financial burdens and dermatological complications and may have mental and psychological consequences. It is important to note that certain cimicids with a preference for specific hosts (birds and bats) use humans as an alternative host, and some cimicids have been reported to willingly feed on human blood. In addition, members of the Cimicidae family can lead to economic burdens and certain species are the vectors for pathogens responsible for diseases. Therefore, in this review, we aim to provide an update on the species within the Cimicidae family that have varying medical and veterinary impacts, including their distribution and their associated microorganisms. Various microbes have been documented in bed bugs and certain important pathogens have been experimentally documented to be passively transmitted by bed bugs, although no conclusive evidence has yet associated them with epidemiological outbreaks. Additionally, among the studied cimicids (bat bugs, chicken bugs, and swallow bugs), only the American swallow bug has been considered to be a vector of several arboviruses, although there is no proven evidence of transmission to humans or animals. Further studies are needed to elucidate the reason that certain species in the Cimicidae family cannot be biologically involved in transmission to humans or animals. Additional investigations are also required to better understand the roles of Cimicidae family members in the transmission of human pathogens in the field.
First Report of the Pepper Fruit Fly Atherigona orientalis (Schiner 1968) (Diptera: Muscidae) Infesting Commercial Pepper Crops in Greece
Authors: Roditakis Emmanouil , Kremi Katerina , Mylona Kyriaki , Georgousis Vasilios , Avtzis Dimitrios N. , Simoglou Konstantinos B.
Published: April 2023

The pepper fruit fly Atherigona orientalis (Schiner 1968) (Diptera: Muscidae) is a cosmopolitan tropical pest which has been recently recorded in several European countries. The biology of the pest has been primarily associated not only with decomposing fruits and vegetables, but even vertebrate and invertebrate carrion, dung and faeces. Relatively recently, A. orientalis has been reported as a primary pest of pepper fruits as well. In this short communication, we report, for the first time in Greece and, to the best of our knowledge, in Europe, cases of pepper fruit fly damage to pepper fruits in commercial greenhouse crops (in Crete in 2022). In this direction, possible implications and concerns regarding the occurrence of this pest in Crete are discussed.
Retrospective Analysis of the Effectiveness of Oral Semaglutide in Type 2 Diabetes Mellitus and Its Effect on Cardiometabolic Parameters in Japanese Clinical Settings
Authors: Yamada Hodaka , Yoshida Masashi , Funazaki Shunsuke , Morimoto Jun , Tonezawa Shiori , Takahashi Asuka , Nagashima Shuichi , Masahiko Kimura , Kiyoshi Otsuka , Hara Kazuo
Published: April 2023

Glucagon-like peptide-1 receptor agonists (GLP-1RA) have a more potent glycated hemoglobin (HbA1c)-lowering effect than existing therapies and are widely used for treating type 2 diabetes mellitus (T2DM). Once-daily oral semaglutide is the world’s first oral GLP-1RA. This study aimed to provide real-world data on oral semaglutide in Japanese patients with T2DM and its effects on cardiometabolic parameters. This was a single-center retrospective observational study. We examined changes in HbA1c and body weight (BW) and the rate of achieving HbA1c < 7% after 6 months of oral semaglutide treatment in Japanese patients with T2DM. Furthermore, we examined differences in the efficacy of oral semaglutide with multiple patient backgrounds. A total of 88 patients were included in this study. Overall, the mean (standard error of the mean) HbA1c at 6 months decreased by −1.24% (0.20%) from baseline, and BW at 6 months (n = 85) also decreased by −1.44 kg (0.26 kg) from baseline. The percentage of patients who achieved HbA1c < 7% changed significantly from 14% at baseline to 48%. HbA1c decreased from baseline regardless of age, sex, body mass index, chronic kidney disease, or diabetes duration. Additionally, alanine aminotransferase, total cholesterol, triglyceride, and non-high-density lipoprotein cholesterol were significantly reduced from baseline. Oral semaglutide may be an effective option for the intensification of therapy in Japanese patients with T2DM who have inadequate glycemic control with existing therapy. It may also reduce BW and improve cardiometabolic parameters.
Nutritional Care Practices in Geriatric Rehabilitation Facilities across Europe: A Cross-Sectional Study
Authors: Everink Irma H. J. , Grund Stefan , Benzinger Petra , de Vries Anne , Gordon Adam L. , van Wijngaarden Janneke P. , Bauer Jürgen M. , Schols Jos M. G. A.
Published: April 2023

Many patients in geriatric rehabilitation (GR) are physically frail at the time of admission and suffer from malnutrition and sarcopenia, which may worsen rehabilitation outcomes. This study aims to obtain insight into the current nutritional care practices in GR facilities across Europe. Methods: In this cross-sectional study, a questionnaire focused on nutritional care practices in GR was distributed across experts in EUGMS member countries. Data were analyzed by using descriptive statistics. Results: In total, 109 respondents working in 25 European countries participated, and the results showed that not all GR patients were screened and treated for malnutrition, and not all participants used (inter)national guidelines when performing nutritional care. The results also showed variations across European geographical areas related to screening and treatment of malnutrition, sarcopenia, and frailty. Even though the participants underlined the importance of dedicating time to nutritional care, they experienced barriers in its implementation, which were mostly due to a lack of resources. Conclusion: As malnutrition, sarcopenia, and frailty are often present in patients admitted to GR, in addition to being interrelated, it is recommended to develop an integrated approach to screening and treatment of all three clinical problems.
Continuing Challenges in the Definitive Diagnosis of Cushing’s Disease: A Structured Review Focusing on Molecular Imaging and a Proposal for Diagnostic Work-Up
Authors: Slagboom Tessa N. A. , Stenvers Dirk Jan , van de Giessen Elsmarieke , Roosendaal Stefan D. , de Win Maartje M. L. , Bot Joseph C. J. , Aronica Eleonora , Post René , Hoogmoed Jantien , Drent Madeleine L. , Pereira Alberto M.
Published: April 2023

The definitive diagnosis of Cushing’s disease (CD) in the presence of pituitary microadenoma remains a continuous challenge. Novel available pituitary imaging techniques are emerging. This study aimed to provide a structured analysis of the diagnostic accuracy as well as the clinical use of molecular imaging in patients with ACTH-dependent Cushing’s syndrome (CS). We also discuss the role of multidisciplinary counseling in decision making. Additionally, we propose a complementary diagnostic algorithm for both de novo and recurrent or persistent CD. A structured literature search was conducted and two illustrative CD cases discussed at our Pituitary Center are presented. A total of 14 CD (n = 201) and 30 ectopic CS (n = 301) articles were included. MRI was negative or inconclusive in a quarter of CD patients. 11C-Met showed higher pituitary adenoma detection than 18F-FDG PET–CT (87% versus 49%). Up to 100% detection rates were found for 18F-FET, 68Ga-DOTA-TATE, and 68Ga-DOTA-CRH, but were based on single studies. The use of molecular imaging modalities in the detection of pituitary microadenoma in ACTH-dependent CS is of added and complementary value, serving as one of the available tools in the diagnostic work-up. In selected CD cases, it seems justified to even refrain from IPSS.
Practical Aspects of Upper Gastrointestinal Bleeding in Children
Authors: Sur Lucia Maria , Armat Ionel , Sur Genel , Tisa Ioana Badiu , Bordea Madalina Adriana , Lupan Iulia , Samasca Gabriel , Lazar Calin
Published: April 2023

Upper gastrointestinal bleeding (UGB) in children is a potentially life-threatening condition that represents a challenge for pediatricians and pediatric surgeons. It is defined as bleeding from any location within the upper esophagus to the ligament of Treitz. UGB can have many causes that vary with age. The impact on the child is often proportional to the amount of blood lost. This can range from mild bleeding that is unlikely to cause hemodynamic instability, to massive bleeding that requires admission to the intensive care unit. Proper and prompt management are very important factors in reducing morbidity and mortality. This article aims to summarize current research regarding the diagnosis and treatment of UGB. Most of the data used in the literature published on this subject is extrapolated from adulthood.
Soluble PCSK9 Inhibition: Indications, Clinical Impact, New Molecular Insights and Practical Approach—Where Do We Stand?
Authors: Bellino Michele , Galasso Gennaro , Silverio Angelo , Tedeschi Michele , Formisano Ciro , Romei Stefano , Esposito Luca , Cancro Francesco Paolo , Vassallo Maria Giovanna , Accarino Giulio , Verdoia Monica , Di Muro Francesca Maria , Vecchione Carmine , De Luca Giuseppe
Published: April 2023

Current research on cardiovascular prevention predominantly focuses on risk-stratification and management of patients with coronary artery disease (CAD) to optimize their prognosis. Several basic, translational and clinical research efforts aim to determine the etiological mechanisms underlying CAD pathogenesis and to identify lifestyle-dependent metabolic risk factors or genetic and epigenetic parameters responsible for CAD occurrence and/or progression. A log-linear association between the absolute exposure of LDL cholesterol (LDL-C) and the risk of atherosclerotic cardio-vascular disease (ASCVD) was well documented over the year. LDL-C was identified as the principal enemy to fight against, and soluble proprotein convertase subtilisin kexin type 9 (PCSK9) was attributed the role of a powerful regulator of blood LDL-C levels. The two currently available antibodies (alirocumab and evolocumab) against PCSK9 are fully human engineered IgG that bind to soluble PCSK9 and avoid its interaction with the LDLR. As documented by modern and dedicated “game-changer” trials, antibodies against soluble PCSK9 reduce LDL-C levels by at least 60 percent when used alone and up to 85 percent when used in combination with high-intensity statins and/or other hypolipidemic therapies, including ezetimibe. Their clinical indications are well established, but new areas of use are advocated. Several clues suggest that regulation of PCSK9 represents a cornerstone of cardiovascular prevention, partly because of some pleiotropic effects attributed to these newly developed drugs. New mechanisms of PCSK9 regulation are being explored, and further efforts need to be put in place to reach patients with these new therapies. The aim of this manuscript is to perform a narrative review of the literature on soluble PCSK9 inhibitor drugs, with a focus on their indications and clinical impact.
Role of Doxycycline as an Osteoarthritis Disease-Modifying Drug
Authors: Shanmugasundaram Saseendar , Solanki Ketansinh , Saseendar Samudeeswari , Chavada Vijay K. , D’Ambrosi Riccardo
Published: April 2023

Doxycycline is a drug that has been proposed to modify osteoarthritis (OA) progression, in addition to its role as an antibiotic. However, available evidence thus far comprises sporadic reports, with no consensus on its benefits. Hence, this review attempts to analyze the evidence available thus far on the role of doxycycline as a disease-modifying osteoarthritis drug (DMOAD) in knee osteoarthritis. The earliest evidence of doxycycline in OA appeared in 1991 when doxycycline was found to inhibit the type XI collagenolytic activity of extracts from the human osteoarthritic cartilage, and gelatinase and tetracycline were found to inhibit this metalloproteinase activity in articular cartilage in vivo, which could modify cartilage breakdown in osteoarthritis. Apart from the inhibition of cartilage damage by metalloproteinases (MMPs) and other cartilage-related mechanisms, doxycycline also affects the bone and interferes with many enzyme systems. The most significant finding after reviewing various studies was that doxycycline has a definitive role in structural changes in osteoarthritis progression and radiological joint space width, but its role in the improvement of clinical outcomes as a DMOAD has not been established. However, there is much of a gap and lack of evidence in this regard. Doxycycline, as an MMP inhibitor, has theoretical advantages for clinical outcomes, but the present studies reveal only beneficial structural changes in osteoarthritis and very minimal or nonexistent advantages in clinical outcomes. Current evidence does not favor the regular use of doxycycline for the treatment of osteoarthritis as an individual treatment option or in combination with others. However, multicenter large cohort studies are warranted to determine the long-term benefits of doxycycline.
A Supplement with Ribes Nigrum, Boswellia Serrata, Bromelain and Vitamin D to Stop Local Inflammation in Chronic Sinusitis: A Case-Control Study
Authors: De Luca Pietro , D’Ascanio Luca , Cingolani Cristina , Latini Gino , Grigaliute Egle , Di Mauro Paola , Ralli Massimo , La Mantia Ignazio , Di Stadio Arianna
Published: April 2023

Although chronic sinusitis widely affects the adult population, the treatments currently used did not always satisfactorily solve the symptoms. Traditional therapy with steroids and antibiotics presents risks and benefits and the new drugs, i.e., monoclonal antibody, are valid solutions despite being quite expensive. Natural molecules could be a valid treatment that combines good efficacy and low price. We conducted a case -control study to evaluate the benefit of an oral supplement with Ribes nigrum, Boswellia serrata, Bromelain and Vitamin D on chronic sinusitis symptoms. 60 patients were randomly assigned to one of the three groups: control using nasal steroids only, treatment 1 using nasal steroid and 1 dose of the oral supplement for 30 days and treatment 2 in which patients used nasal steroid and two oral supplement doses daily for 15 days. Conditions of the nasal mucosa and a blood sample (WBC, IgE and CRP) were analyzed at T0, T1 (15 days after treatment) and T2 (30 days after treatment. Patients treated with the supplement improved their nasal findings (hyperemia of mucosa and rhinorrhea) with statistically significant differences from the control. Our preliminary data suggest that the addition of supplement containing Ribes nigrum, Boswellia serrata, Vitamin D and Bromelain to the traditional local therapy (nasal spray with cortisone) can be a supporting therapy to modulate the local inflammation in the nose in patients affected by chronic sinusitis.
Immunomodulatory Effects Mediated by Nano Amorphous Calcium Phosphate/Chitosan Oligosaccharide Lactate Coatings Decorated with Selenium on Titanium Implants
Authors: Pantović Pavlović Marijana R. , Ignjatović Nenad L. , Panić Vladimir V. , Mirkov Ivana I. , Kulaš Jelena B. , Malešević Anastasija Lj. , Pavlović Miroslav M.
Published: April 2023

The aim of this work is in situ anodization/anaphoretic deposition of a nano amorphous calcium phosphate (ACP)/chitosan oligosaccharide lactate (ChOL) multifunctional hybrid coating decorated with selenium (Se) on a titanium substrate and in vivo investigation of its immunomodulatory and anti-inflammatory effect. Investigating phenomena at the implant–tissue interface of interest for controlled inflammation and immunomodulation was also the aim of the research. In our earlier research, we designed coatings based on ACP and ChOL on titanium with anticorrosive, antibacterial and biocompatible properties, while in the presented results we show that selenium addition makes this coating an immunomodulator. The immunomodulatory effect of the novel hybrid coating is characterized by the examination of the functional aspects in the tissue around the implant (in vivo): proinflammatory cytokines’ gene expression, M1 (iNOS) and M2 (Arg1) macrophages, fibrous capsule formation (TGF-β) and vascularization (VEGF). The EDS, FTIR and XRD analyses prove the formation of a ACP/ChOL/Se multifunctional hybrid coating on Ti and the presence of Se. A higher M2/M1 macrophage ratio in the ACP/ChOL/Se-coated implants compared to pure titanium implants (a higher level of Arg1 expression) is noted at all time points examined (after 7, 14 and 28 days). Lower inflammation measured by gene expression of proinflammatory cytokines IL-1β and TNF, lower expression of TGF-β in the surrounding tissue and higher IL-6 expression (solely at day 7 post-implantation) is noted in presence of the ACP/ChOL/Se-coated implants.