bluuebunny/crossref_metadata_2025 huggingface dataset:
Tomato Residue Management from a Biorefinery Perspective and towards a Circular Economy
Authors: Almeida Patrícia V. , Gando-Ferreira Licínio M. , Quina Margarida J.
Published: June 2024

The tomato industry is a relevant socio-economic activity in the European Union, while it generates a large variety of residues. Tomatoes unfit for consumption, tomato peels, seeds, industrial pomace, and plants are examples of residues of this industry. Commonly, some of the residues can be left in the field, composted, used for animal feeding, or valorized through anaerobic digestion. However, more economic value can be attributed to these residues if a biorefinery approach is applied. Indeed, many value-added compounds can be obtained by the integration of different processes while closing the carbon and nutrient loops. The extraction of bioactive compounds followed by anaerobic digestion and composting seems to be a viable proposal for a biorefinery approach. Thus, this study aims to review the biorefinery strategies for valorizing tomato residues, highlighting the main processes proposed. The recovery of lycopene, β-carotene, and phenolic compounds has been widely studied at the lab scale, while energy recovery has already been applied at the industrial scale. Although techno-economic analysis is scarce for tomato residue valorization processes, positive net present values (NPV) and low payback times (PBT) have been reported in the literature. Thus, more work comparing multiple extraction technologies and biorefinery strategies coupled with economic and environmental assessment should be performed to select the most promising management route for tomato residues.
Research and Technologies to Reduce Grain Postharvest Losses: A Review
Authors: Nath Bidhan , Chen Guangnan , O’Sullivan Cherie M. , Zare Dariush
Published: June 2024

Reducing postharvest losses offers a significant opportunity to enhance food availability without requiring extra production resources. A substantial portion of cereal grain goes to waste annually due to a lack of science-based knowledge, unconscious handling practices, suboptimal technical efficiency, and inadequate infrastructure. This article extensively reviews losses occurring during postharvest operations across various crops, examining diverse postharvest operations in different countries. Recent advancements in postharvest technology research are thoroughly discussed. The primary obstacles and challenges hindering the adoption and implementation of postharvest technologies are also explored. The appropriate postharvest technology relies on specific factors, including the kind of crops, production locales, seasons, and existing environmental and socioeconomic conditions.
Using Event-Related Potentials to Evidence the Visual and Semantic Impact: A Pilot Study with N400 Effect and Food Packaging
Authors: Rojas Juan-Carlos , Contero Manuel , Vergara Margarita , Higuera-Trujillo Juan Luis
Published: June 2024

Packaging design is pivotal in motivating consumer decisions, as a key communication tool from creation to purchase. Currently, the interpretation and evaluation of packaging’s impact are shifting toward non-traditional methods. This pilot study evaluated the packaging perception of York Ham and Turkey Breast products. The event-related potential (ERP) technique, the methodology priming words (positive and negative), and target images (original and modified packaging) were applied. A total of 23 participants were sampled using a 32-channels scalp elastic electrode cap and viewed 200 trials of word–image matching. Participants responded whether the images and adjectives matched or not, using the two groups of images. The results demonstrate an N400 effect in the parietal area. This region was observed to show evidence of cognitive processing related to congruency or incongruency, by contrasting the priming and target of this study. The evaluation positioned the York Ham packaging as the best rated. The findings show a relevant contribution to ERPs and research related to the food packaging perception.
Exploration of New Lipid Nutrients and Their Characterization in Herbal Teas Using Non-Targeted Liquid Chromatography–Mass Spectrometry
Authors: Malek Md , B. Gowda Siddabasave , M. Gangadhara Rachana , Gowda Divyavani , Hui Shu-Ping
Published: June 2024

Herbal teas are blends of leaves, seeds, fruits, and flowers from various plants that provide relaxation, anti-inflammatory benefits, and immune system support for conditions such as diabetes and asthma. Despite their health benefits, comprehensive lipidomic data on herbal teas are limited in the literature. We used non-targeted liquid chromatography–linear ion trap orbitrap mass spectrometry to identify and correlate the lipid species in the following six herbal tea samples: fennel, ginger, juniper, lemon peel, orange peel, and rosehip. A total of 204 lipid molecular species were identified, and multivariate analysis revealed a significant difference between lipid species in herbal teas. Saturated fatty acids (SFAs) and polyunsaturated fatty acids (PUFAs) are significantly abundant in juniper, including ω-3 and ω-6 fatty acids, followed by fennel. Cluster correlations showed that ginger contained mainly sphingolipids and lysophospholipids, whereas fennel was rich in phospholipids. No significant variations in the content of triacylglycerols were observed in any of the herbal teas analyzed. The ratio of PUFAs to SFAs in herbal teas showed that orange peel had the highest ratio, followed by lemon peel and fennel, indicating their potential health benefits. In addition, using high-resolution mass spectrometry, various lipids such as fatty acid esters of hydroxy fatty acids and N-acyl-lysophosphatidylethanolamines were identified and characterized in these herbal teas. This study provides a comprehensive lipid analysis and detailed characterization of lipids in six herbal teas, highlighting their plausible applications in the field of nutrition and various food industries for the development of functional foods.
Elucidating the Interaction of Indole-3-Propionic Acid and Calf Thymus DNA: Multispectroscopic and Computational Modeling Approaches
Authors: Wei Yushi , Zhang Dan , Pan Junhui , Gong Deming , Zhang Guowen
Published: June 2024

Indole-3-propionic acid (IPA) is a plant growth regulator with good specificity and long action. IPA may be harmful to human health because of its accumulation in vegetables and fruits. Therefore, in this study, the properties of the interaction between calf thymus DNA (ctDNA) and IPA were systematically explored using multispectroscopic and computational modeling approaches. Analysis of fluorescence spectra showed that IPA binding to ctDNA to spontaneously form a complex was mainly driven by hydrogen bonds and hydrophobic interaction. DNA melting analysis, viscosity analysis, DNA cleavage study, and circular dichroism measurement revealed the groove binding of IPA to ctDNA and showed that the binding did not significantly change ctDNA confirmation. Furthermore, molecular docking found that IPA attached in the A-T rich minor groove region of the DNA. Molecular dynamics simulation showed that DNA and IPA formed a stable complex and IPA caused slight fluctuations for the residues at the binding site. Gel electrophoresis experiments showed that IPA did not significantly disrupt the DNA structure. These findings may provide useful information on the potential toxicological effects and environmental risk assessments of IPA residue in food at the molecular level.
Advances in Carbon Xerogels: Structural Optimization for Enhanced EDLC Performance
Authors: Choi Jongyun , Jung Ji Chul , Jung Wonjong
Published: June 2024

This review explores the recent progress on carbon xerogels (CXs) and highlights their development and use as efficient electrodes in organic electric double-layer capacitors (EDLCs). In addition, this work examines how the adjustment of synthesis parameters, such as pH, polymerization duration, and the reactant-to-catalyst ratio, crucially affects the structure and electrochemical properties of xerogels. The adaptability of xerogels in terms of modification of their porosity and structure plays a vital role in the improvement of EDLC applications as it directly influences the interaction between electrolyte ions and the electrode surface, which is a key factor in determining EDLC performance. The review further discusses the substantial effects of chemical activation with KOH on the improvement of the porous structure and specific surface area, which leads to notable electrochemical enhancements. This structural control facilitates improvement in ion transport and storage, which are essential for efficient EDLC charge–discharge (C–D) cycles. Compared with commercial activated carbons for EDLC electrodes, CXs attract interest for their superior surface area, lower electrical resistance, and stable performance across diverse C–D rates, which underscore their promising potential in EDLC applications. This in-depth review not only summarizes the advancements in CX research but also highlights their potential to expand and improve EDLC applications and demonstrate the critical role of their tunable porosity and structure in the evolution of next-generation energy storage systems.
Representing Zooplankters: An Example from the Foraminifera
Authors: Scott George H.
Published: June 2024

Because of their excellent preservation record, testate zooplankters provide valuable proxy ocean climate data through the Quaternary–Recent. Commonly, specimen abundances are sought, which are time-consuming to collect manually and require taxonomic expertise. While machine learning models obviate these problems, it is questioned whether the current use of specimens selected by experts to train the models impartially captures the variation within the source populations. To illustrate the potential value of the latter and their relevance to the selection of representative specimens, the 2D outline shape of the planktonic foraminifer Truncorotalia crassaformis from four globally distributed, late-Quaternary–modern collections is examined. Large intra-sample variation is attributed to changes in the size and shape of the last-formed chamber, which often departs radically from its predecessors. Similar outlines occur in each collection, and no single axial shape is dominant when the aggregated data, aligned on their centroids and adjusted for size and position, are projected onto their principal components. Several partitions based on distance from the centroid of the standardized data are considered as sources of representative specimens, with that at ±1.645σ (standard deviations, nominally 90%) suggested as suitable. This procedure obviates the need for expert-based consensus sampling; for greater environmental resolution, it can be applied to individual water mass samples. It assists, but does not fully resolve, the following basic diagnostic question: which characters separate Truncorotalia crassaformis from its relatives?
Parents’ Awareness of Infectious Diseases Epidemiology in Poland and Ukraine
Authors: Stępień Maciej , Cholewik Martyna , Żuromski Jan , Bieńkowski Carlo , Pokorska-Śpiewak Maria
Published: June 2024

Background: There has been a decline in vaccine-related confidence in Ukraine over the past few years, resulting in high rates of infectious diseases. Due to the arrival of a large number of refugees in Poland following the outbreak of war in Ukraine in February 2022, the risk of infectious diseases in Poland among children and adults has increased. The present study aimed to analyze the relationship between parents’ knowledge of the epidemiological situation of infectious diseases in Poland and Ukraine and socio-demographic factors and their attitudes towards vaccination. Material and methods: A cross-sectional survey study was designed. Data were collected through an online questionnaire between November 2022 and January 2023, where the inclusion criteria was having a child under 18 years of age. Study participants’ stratification was based on responses to seven knowledge questions; those who answered all questions correctly were allocated to group 1, and the others to group 2 for further analysis. Results: A total of 547 parents were included. Their median age was 34 years [IQR: 31–39]. There were 233 (42.60%) participants who answered all the knowledge questions correctly. Respondents from group 1 were older (p = 0.033), were more likely to be in favor of recommended vaccination (p = 0.040), to be vaccinated with four doses against SARS-CoV-2 (p = 0.014), to have their children vaccinated against SARS-CoV-2 (p < 0.001), and to believe that the influx of migrants from Ukraine would increase the incidence rate of infectious diseases in Poland in the future (p < 0.001). They also declared awareness of the impact of migration on the epidemiological situation in Poland (p < 0.001) more often. According to the logistic regression model, older parents (OR = 1.31, p = 0.029), those who were willing to receive additional vaccinations due to migration (OR = 4.29, p = 0.003), those who were aware of the impact of migration on the epidemiological situation (OR = 2.38, p < 0.001), and those who believed that migration would have affected the incidence rate of infectious diseases in Poland (OR = 2.28, p = 0.003) were significantly more likely to belong to group 1. However, parents who were willing to vaccinate their children with additional vaccinations due to migration were significantly less likely to answer all the questions correctly (OR = 0.21, p = 0.002). Conclusions: Awareness of the epidemiological situation in Poland and Ukraine among parents is related to a greater awareness of the impact of migration and the use of recommended vaccinations and those against SARS-CoV-2. Additional vaccinations should be further promoted among both Poles and migrants.
Anthropogenic Activity in the Topo-Climatic Interaction of the Tapajós River Basin, in the Brazilian Amazon
Authors: Franco Vânia dos Santos , Lima Aline Maria Meiguins de , Oliveira Rodrigo Rafael Souza de , Souza Everaldo Barreiros de , Sodré Giordani Rafael Conceição , Santos Diogo Correa , Adami Marcos , Serrão Edivaldo Afonso de Oliveira , Dias Thaiane Soeiro da Silva
Published: June 2024

This research aimed to analyze the relationship between deforestation (DFT) and climatic variables during the rainy (CHU+) and less-rainy (CHU−) seasons in the Tapajós River basin. Data were sourced from multiple institutions, including the Climatic Research Unit (CRU), Center for Weather Forecasts and Climate Studies (CPTEC), PRODES Program (Monitoring of Brazilian Amazon Deforestation Project), National Water Agency (ANA) and National Centers for Environmental Prediction/National Oceanic and Atmospheric Administration (NCEP/NOAA). The study assessed anomalies (ANOM) in maximum temperature (TMAX), minimum temperature (TMIN) and precipitation (PREC) over three years without the occurrence of the El Niño–Southern Oscillation (ENSO) atmospheric–oceanic phenomenon. It also examined areas with higher DFT density using the Kernel methodology and analyzed the correlation between DFT and climatic variables. Additionally, it assessed trends using the Mann–Kendall technique for both climatic and environmental data. The results revealed significant ANOM in TEMP and PREC. In PREC, the highest values of ANOM were negative in CHU+. Regarding temperature, the most significant values were positive ANOM in the south, southwest and northwestern regions of the basin. Concerning DFT density, data showed that the highest concentration was of medium density, primarily along the highways. The most significant correlations were found between DFT and TEMP during the CHU− season in the Middle and Lower Tapajós sub-basins, regions where the forest still exhibits more preserved characteristics. Furthermore, the study identified a positive trend in TEMP and a negative trend in PREC.
Developing Problematic Performance Value Scores: Binding Routine Activity Performance, Environmental Barriers, and Health Conditions
Authors: Choi Jimin , Park JiYoung
Published: June 2024

Background: Community design features, such as sidewalks and street crossings, present significant challenges for individuals with disabilities, hindering their physical performance and social integration. However, limited research has been conducted on the application of Universal Design (UD) to address these challenges, particularly concerning specific demographic groups and population cohorts. Understanding the influence of environmental features on physical performance is crucial for developing inclusive solutions like UD, which can enhance usability and social integration across diverse populations. Objective: This study aims to bridge this gap by investigating the complex relationships between environmental barriers, health conditions, and routine activity performance. An index was developed to evaluate users’ UD performance based on functional capacity, providing scientifically rigorous and objectively measured evidence of UD effectiveness in creating inclusive built environments. Method: Using data from the Problematic Activities Survey (PAS) conducted in the U.S., Canada, and Australia and targeting individuals with and without functional limitations, multinomial logit models were employed to estimate the probabilities of encountering performance problems. This analysis led to the development of the Problematic Performance Value (PPV) score. Results: The results demonstrated significant disparities in PPVs across various health conditions, particularly concerning curb ramps. Individuals facing mobility issues in their legs/feet, arms/hands, or back/neck encounter more pronounced challenges, especially when curb ramps lack proper design elements. Similarly, individuals with vision impairments face heightened difficulties with traffic signals, particularly due to issues with audible signal systems. These findings underscore the importance of addressing micro-level environmental challenges to accommodate individuals with varying functional capacities effectively. Conclusions: By providing insights into the most problematic daily activities encountered by diverse populations, the PPV score serves as a valuable indicator for guiding environmental design improvements and promoting equitable space usage. This can be used to guide improved UD solutions and decide areas of concentration by providing generalized information on specific environmental features that contribute to user performance.
Childhood Adversities and the ATTACHTM Program’s Influence on Immune Cell Gene Expression
Authors: Yu Zhiyuan , Cole Steve , Ross Kharah , Hart Martha , Anis Lubna , Letourneau Nicole
Published: June 2024

Objective: To determine whether maternal Adverse Childhood Experiences (ACEs) are (a) associated with increased inflammatory gene expression in mother–child dyads and (b) whether a parenting intervention (ATTACH™) moderates the association between maternal ACEs and mother and/or child inflammatory gene expression. Methods: Twenty mother–child dyads, recruited from a domestic violence shelter in Calgary, AB, Canada, were randomized into an ATTACH™ parenting intervention group (n = 9) or a wait-list control group (n = 11). Maternal ACEs were assessed. The mothers and children each provided one non-fasting blood sample after the intervention group completed the ATTACH™ program, which was assayed to quantify the Conserved Transcriptional Response to Adversity (CTRA) score, indicating inflammatory gene expression profile. Mixed-effect linear models were used, separately in mothers and children, to examine the associations between CTRA score, maternal ACEs, and the ACEs-by-intervention group interaction term. The covariates were age, sex, ethnicity, and maternal medication use. Results: Higher maternal ACEs were associated with higher child CTRA scores (b = 0.123 ± SE 0.044, p = 0.005), indicating an increased pro-inflammatory gene expression profile. The ATTACH™ parenting intervention moderated this association between maternal ACEs and child CTRA scores (b = 0.328 ± SE 0.133, p = 0.014). In mothers, the ACEs-by-intervention interaction terms were insignificant (p = 0.305). Conclusions: Maternal ACEs could exert an intergenerational impact on child inflammatory activity, and this association could be moderated by participating in the ATTACH™ parenting intervention.
The Cumulative Effect of Expanding the Breadth and Scope of Coverage for Substance Use Disorder Treatment on Behavioral Health Acute Inpatient Admissions: Evidence from Virginia Medicaid
Authors: Salehian Shiva , Cunningham Peter , Barnes Andrew , Lee Shoou-Yih Daniel
Published: June 2024

We evaluated the impact of Medicaid policies in Virginia (VA), namely the Addiction and Recovery Treatment Services (ARTS) program and Medicaid expansion, on the number of behavioral health acute inpatient admissions from 2016 to 2019. We used Poisson fixed-effect event study regression and compared average proportional differences in admissions over three time periods: (1) prior to ARTS; (2) following ARTS but before Medicaid expansion; (3) post-Medicaid expansion. The number of behavioral health acute inpatient admissions decreased by 2.6% (95% CI [−5.1, −0.2]) in the first quarter of 2018 and this decrease gradually intensified by 4.9% (95% CI [−7.5, −2.4]) in the fourth quarter of 2018 compared to the second quarter of 2017 (beginning of ARTS) in VA relative to North Carolina (NC). Following the first quarter of 2019 (beginning of Medicaid expansion), decreases in VA admissions became larger relative to NC. The average proportional difference in admissions estimated a decrease of 2.7% (95% CI, [−4.1, −0.8]) after ARTS but before Medicaid expansion and a decrease of 2.9% (95% CI, [−6.1, 0.4]) post-Medicaid expansion compared to pre-ARTS in VA compared to NC. Behavioral health acute inpatient admissions in VA decreased following ARTS implementation, and the decrease became larger after Medicaid expansion.
Smart Speakers as an Environmental Control Unit for Severe Motor Dependence: The Case of a Young Adult with Duchenne Muscular Dystrophy
Authors: Tavares Rafael , Inácio Andreia , Sousa Helena , Ribeiro Jaime
Published: June 2024

Duchenne muscular dystrophy (DMD) is a disease that primarily affects males and causes a gradual loss of muscle strength. This results in a deterioration of motor skills and functional mobility, which can impact the performance of various occupations. Individuals with DMD often rely heavily on caregivers to assist with daily activities, which can lead to caregiver burden. A case study was conducted to explore and describe potential variations in the performance of a young adult diagnosed with DMD and his caregivers resulting from the integration of smart speakers (SS)-controlled Internet of Things (IoT) devices in the home environment. The study also examined the potential of SS as an environment control unit (ECU) and analysed variations in caregiver burden. Smart devices and SS were installed in the most frequently used spaces, namely, the bedroom and living room. The study employed WebQDA software to perform content analysis and Microsoft Excel to calculate the scores of the structured instruments. The implementation of the IoT-assisted environment compensated for previously physical tasks, resulting in a slight increase in independent performance and reduced demands on caregivers.
Financial Decisions Based on Zero-Sum Games: New Conceptual and Mathematical Outcomes
Authors: Angelini Pierpaolo
Published: June 2024

All the n possible returns on a financial asset are the components of an element of a linear space over R. This paper shows how to transfer all these n possible returns on a one-dimensional straight line. In this research work, two or more than two financial assets are studied. More than two financial assets are always studied in pairs, so they are treated inside the budget set of a given decision-maker. Two univariate financial assets give rise to a bivariate financial asset characterized by a bivariate (two-dimensional) distribution of probability. This research work shows how constrained choices being made by a given decision-maker under conditions of uncertainty and riskiness maximize his utility of an ordinal nature. For this reason, prevision bundles are dealt with. Furthermore, every choice identifies a zero-sum game. Since a specific kind of choice associated with two or more than two objects is investigated, new conceptual and mathematical outcomes related to financial decisions are shown.
A Novel 10-Base Pair Deletion in the First Exon of GmHY2a Promotes Hypocotyl Elongation, Induces Early Maturation, and Impairs Photosynthetic Performance in Soybean
Authors: Zhu Xiaobin , Wang Haiyan , Li Yuzhuo , Rao Demin , Wang Feifei , Gao Yi , Zhong Weiyu , Zhao Yujing , Wu Shihao , Chen Xin , Qiu Hongmei , Zhang Wei , Xia Zhengjun
Published: June 2024

Plants photoreceptors perceive changes in light quality and intensity and thereby regulate plant vegetative growth and reproductive development. By screening a γ irradiation-induced mutant library of the soybean (Glycine max) cultivar “Dongsheng 7”, we identified Gmeny, a mutant with elongated nodes, yellowed leaves, decreased chlorophyll contents, altered photosynthetic performance, and early maturation. An analysis of bulked DNA and RNA data sampled from a population segregating for Gmeny, using the BVF-IGV pipeline established in our laboratory, identified a 10 bp deletion in the first exon of the candidate gene Glyma.02G304700. The causative mutation was verified by a variation analysis of over 500 genes in the candidate gene region and an association analysis, performed using two populations segregating for Gmeny. Glyma.02G304700 (GmHY2a) is a homolog of AtHY2a in Arabidopsis thaliana, which encodes a PΦB synthase involved in the biosynthesis of phytochrome. A transcriptome analysis of Gmeny using the Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed changes in multiple functional pathways, including photosynthesis, gibberellic acid (GA) signaling, and flowering time, which may explain the observed mutant phenotypes. Further studies on the function of GmHY2a and its homologs will help us to understand its profound regulatory effects on photosynthesis, photomorphogenesis, and flowering time.
The Complex Intracellular Lifecycle of Staphylococcus aureus Contributes to Reduced Antibiotic Efficacy and Persistent Bacteremia
Authors: Volk Cecilia F. , Proctor Richard A. , Rose Warren E.
Published: June 2024

Staphylococcus aureus bacteremia continues to be associated with significant morbidity and mortality, despite improvements in diagnostics and management. Persistent infections pose a major challenge to clinicians and have been consistently shown to increase the risk of mortality and other infectious complications. S. aureus, while typically not considered an intracellular pathogen, has been proven to utilize an intracellular niche, through several phenotypes including small colony variants, as a means for survival that has been linked to chronic, persistent, and recurrent infections. This intracellular persistence allows for protection from the host immune system and leads to reduced antibiotic efficacy through a variety of mechanisms. These include antimicrobial resistance, tolerance, and/or persistence in S. aureus that contribute to persistent bacteremia. This review will discuss the challenges associated with treating these complicated infections and the various methods that S. aureus uses to persist within the intracellular space.
The Role of Copper Overload in Modulating Neuropsychiatric Symptoms
Authors: Manchia Mirko , Paribello Pasquale , Pinna Martina , Faa Gavino
Published: June 2024

Copper is a transition metal essential for growth and development and indispensable for eukaryotic life. This metal is essential to neuronal function: its deficiency, as well as its overload have been associated with multiple neurodegenerative disorders such as Alzheimer’s disease and Wilson’s disease and psychiatric conditions such as schizophrenia, bipolar disorder, and major depressive disorders. Copper plays a fundamental role in the development and function of the human Central Nervous System (CNS), being a cofactor of multiple enzymes that play a key role in physiology during development. In this context, we thought it would be timely to summarize data on alterations in the metabolism of copper at the CNS level that might influence the development of neuropsychiatric symptoms. We present a non-systematic review with the study selection based on the authors’ judgement to offer the reader a perspective on the most significant elements of neuropsychiatric symptoms in Wilson’s disease. We highlight that Wilson’s disease is characterized by marked heterogeneity in clinical presentation among patients with the same mutation. This should motivate more research efforts to disentangle the role of environmental factors in modulating the expression of genetic predisposition to this disorder.
Understanding Hypoxia-Driven Tumorigenesis: The Interplay of HIF1A, DNA Methylation, and Prolyl Hydroxylases in Head and Neck Squamous Cell Carcinoma
Authors: Ostapowicz Julia , Ostrowska Kamila , Rawłuszko-Wieczorek Agnieszka A. , Wojtera Bartosz , Koczot Sabina , Golusiński Wojciech , Suchorska Wiktoria M.
Published: June 2024

Hypoxia-inducible factor 1-alpha (HIF1A) is a key transcription factor aiding tumor cells’ adaptation to hypoxia, regulated by the prolyl hydroxylase family (EGLN1-3) by directing toward degradation pathways. DNA methylation potentially influences EGLN and HIF1A levels, impacting cellular responses to hypoxia. We examined 96 HNSCC patients and three cell lines, analyzing gene expression of EGLN1-3, HIF1A, CA9, VEGF, and GLUT1 at the mRNA level and EGLN1 protein levels. Methylation levels of EGLNs and HIF1A were assessed through high-resolution melting analysis. Bioinformatics tools were employed to characterize associations between EGLN1-3 and HIF1A expression and methylation. We found significantly higher mRNA levels of EGLN3, HIF1A, GLUT1, VEGF, and CA9 (p = 0.021; p < 0.0001; p < 0.0001; p = 0.004, and p < 0.0001, respectively) genes in tumor tissues compared to normal ones and downregulation of the EGLN1 mRNA level in tumor tissues (p = 0.0013). In HNSCC patients with hypermethylation of HIF1A in normal tissue, we noted a reduction in HIF1A mRNA levels compared to tumor tissue (p = 0.04). In conclusion, the differential expression of EGLN and HIF1A genes in HNSCC tumors compared to normal tissues influences patients’ overall survival, highlighting their role in tumor development. Moreover, DNA methylation could be responsible for HIF1A suppression in the normal tissues of HNSCC patients.
A Plasma Pyrophosphate Cutoff Value for Diagnosing Pseudoxanthoma Elasticum
Authors: Rubera Isabelle , Clotaire Laetitia , Laurain Audrey , Destere Alexandre , Martin Ludovic , Duranton Christophe , Leftheriotis Georges
Published: June 2024

Pseudoxanthoma elasticum (PXE) is a rare inherited systemic disease responsible for a juvenile peripheral arterial calcification disease. The clinical diagnosis of PXE is only based on a complex multi-organ phenotypic score and/or genetical analysis. Reduced plasma inorganic pyrophosphate concentration [PPi]p has been linked to PXE. In this study, we used a novel and accurate method to measure [PPi]p in one of the largest cohorts of PXE patients, and we reported the valuable contribution of a cutoff value to PXE diagnosis. Plasma samples and clinical records from two French reference centers for PXE (PXE Consultation Center, Angers, and FAVA-MULTI South Competent Center, Nice) were assessed. Plasma PPi were measured in 153 PXE and 46 non-PXE patients. The PPi concentrations in the plasma samples were determined by a new method combining enzymatic and ion chromatography approaches. The best match between the sensitivity and specificity (Youden index) for diagnosing PXE was determined by ROC analysis. [PPi]p were lower in PXE patients (0.92 ± 0.30 µmol/L) than in non-PXE patients (1.61 ± 0.33 µmol/L, p < 0.0001), corresponding to a mean reduction of 43 ± 19% (SD). The PPi cutoff value for diagnosing PXE in all patients was 1.2 µmol/L, with a sensitivity of 83.3% and a specificity of 91.1% (AUC = 0.93), without sex differences. In patients aged <50 years (i.e., the age period for PXE diagnosis), the cutoff PPi was 1.2 µmol/L (sensitivity, specificity, and AUC of 93%, 96%, and 0.97, respectively). The [PPi]p shows high accuracy for diagnosing PXE; thus, quantifying plasma PPi represents the first blood assay for diagnosing PXE.
In Vivo Expression of Chicken Gut Anaerobes Identifies Carbohydrate- or Amino Acid-Utilising, Motile or Type VI Secretion System-Expressing Bacteria
Authors: Rajova Jana , Zeman Michal , Seidlerova Zuzana , Vlasatikova Lenka , Matiasovicova Jitka , Sebkova Alena , Faldynova Marcela , Prikrylova Hana , Karasova Daniela , Crhanova Magdalena , Kulich Pavel , Babak Vladimir , Volf Jiri , Rychlik Ivan
Published: June 2024

Complex gut microbiota increases chickens’ resistance to enteric pathogens. However, the principles of this phenomenon are not understood in detail. One of the possibilities for how to decipher the role of gut microbiota in chickens’ resistance to enteric pathogens is to systematically characterise the gene expression of individual gut microbiota members colonising the chicken caecum. To reach this aim, newly hatched chicks were inoculated with bacterial species whose whole genomic sequence was known. Total protein purified from the chicken caecum was analysed by mass spectrometry, and the obtained spectra were searched against strain-specific protein databases generated from known genomic sequences. Campylobacter jejuni, Phascolarctobacterium sp. and Sutterella massiliensis did not utilise carbohydrates when colonising the chicken caecum. On the other hand, Bacteroides, Mediterranea, Marseilla, Megamonas, Megasphaera, Bifidobacterium, Blautia, Escherichia coli and Succinatimonas fermented carbohydrates. C. jejuni was the only motile bacterium, and Bacteroides mediterraneensis expressed the type VI secretion system. Classification of in vivo expression is key for understanding the role of individual species in complex microbial populations colonising the intestinal tract. Knowledge of the expression of motility, the type VI secretion system, and preference for carbohydrate or amino acid fermentation is important for the selection of bacteria for defined competitive exclusion products.
Purified Clinoptilolite-Tuff as an Efficient Sorbent for Food-Derived Peanut Allergens
Authors: Ranftler Carmen , Zehentner Magdalena , Pengl Andreas , Röhrich Andreas , Tschegg Cornelius , Nagl Dietmar
Published: June 2024

The avoidance of allergen intake is crucial for persons affected by peanut allergy; however, the cross-contamination of food is common and leads to unpredictable consequences after the consumption of supposedly “safe” food. The aim of the present study was to eliminate harmful traces of peanut allergens from food using purified clinoptilolite-tuff (PCT)—a specially processed zeolite material. Analyses were performed using a peanut ELISA and a Coomassie blue (Bradford) assay. Mimicking conditions of the human gastrointestinal tract demonstrated a higher efficacy of PCT in the intestine (pH 6.8) than in the stomach (pH 1.5). Adsorption rates were fast (<2 min) and indicated high capacities (23 µg and 40 µg per 1 mg of PCT at pH 1.5 and pH 6.8, respectively). Allergenically relevant peanut protein concentrations were sorbed in artificial fluids (32 µg/mL by 4 mg/mL of PCT at pH 1.5 and 80.8 µg/mL by 0.25 mg/mL of PCT at pH 6.8) when imitating a daily dose of 2 g of PCT in an average stomach volume of 500 mL. Experiments focusing on the bioavailability of peanut protein attached to PCT revealed sustained sorption at pH 1.5 and only minor desorption at pH 6.8. Accompanied by gluten, peanut proteins showed competing binding characteristics with PCT. This study therefore demonstrates the potential of PCT in binding relevant quantities of peanut allergens during the digestion of peanut-contaminated food.
Relationship between Hypoxia and Hypercapnia Tolerance and Life Expectancy
Authors: Tregub Pavel P. , Komleva Yulia K. , Kulikov Vladimir P. , Chekulaev Pavel A. , Tregub Oksana F. , Maltseva Larisa D. , Manasova Zaripat Sh. , Popova Inga A. , Andriutsa Natalia S. , Samburova Natalia V. , Salmina Alla B. , Litvitskiy Peter F.
Published: June 2024

The review discusses the potential relationship between hypoxia resistance and longevity, the influence of carbon dioxide on the mechanisms of aging of the mammalian organism, and intermittent hypercapnic–hypoxic effects on the signaling pathways of aging mechanisms. In the article, we focused on the potential mechanisms of the gero-protective efficacy of carbon dioxide when combined with hypoxia. The review summarizes the possible influence of intermittent hypoxia and hypercapnia on aging processes in the nervous system. We considered the perspective variants of the application of hypercapnic–hypoxic influences for achieving active longevity and the prospects for the possibilities of developing hypercapnic–hypoxic training methods.
Non-Specific Lipid Transfer Protein Amb a 6 Is a Source-Specific Important Allergenic Molecule in Ragweed Pollen
Authors: Grijincu Manuela , Tănasie Gabriela , Zbîrcea Lauriana-Eunice , Buzan Maria-Roxana , Tamaș Tudor-Paul , Cotarcă Monica-Daniela , Huțu Ioan , Babaev Elijahu , Stolz Frank , Dorofeeva Yulia , Valenta Rudolf , Păunescu Virgil , Panaitescu Carmen , Chen Kuan-Wei
Published: June 2024

Pollen from common ragweed is an important allergen source worldwide and especially in western and southern Romania. More than 100 million patients suffer from symptoms of respiratory allergy (e.g., rhinitis, asthma) to ragweed pollen. Among the eleven characterized allergens, Amb a 6 is a non-specific lipid transfer protein (nsLTP). nsLTPs are structurally stable proteins in pollen and food from different unrelated plants capable of inducing severe reactions. The goal of this study was to produce Amb a 6 as a recombinant and structurally folded protein (rAmb a 6) and to characterize its physicochemical and immunological features. rAmb a 6 was expressed in Spodoptera frugiperda Sf9 cells as a secreted protein and characterized by mass spectrometry and circular dichroism (CD) spectroscopy regarding molecular mass and fold, respectively. The IgE-binding frequency towards the purified protein was evaluated using sera from 150 clinically well-characterized ragweed-allergic patients. The allergenic activities of rAmb a 6 and the nsLTP from the weed Parietaria judaica (Par j 2) were evaluated in basophil activation assays. rAmb a 6-specific IgE reactivity was associated with clinical features. Pure rAmb a 6 was obtained by insect cell expression. Its deduced molecular weight corresponded to that determined by mass spectrometry (i.e., 10,963 Da). rAmb a 6 formed oligomers as determined by SDS-PAGE under non-reducing conditions. According to multiple sequence comparisons, Amb a 6 was a distinct nsLTP with less than 40% sequence identity to currently known plant nsLTP allergens, except for nsLTP from Helianthus (i.e., 52%). rAmb a 6 is an important ragweed allergen recognized by 30% of ragweed pollen allergic patients. For certain patients, rAmb a 6-specific IgE levels were higher than those specific for the major ragweed allergen Amb a 1 and analysis also showed a higher allergenic activity in the basophil activation test. rAmb a 6-positive patients suffered mainly from respiratory symptoms. The assumption that Amb a 6 is a source-specific ragweed allergen is supported by the finding that none of the patients showing rAmb a 6-induced basophil activation reacted with Par j 2 and only one rAmb a 6-sensitized patient had a history of plant food allergy. Immunization of rabbits with rAmb a 6 induced IgG antibodies which strongly inhibited IgE binding to rAmb a 6. Our results demonstrate that Amb a 6 is an important source-specific ragweed pollen allergen that should be considered for diagnosis and allergen-specific immunotherapy of ragweed pollen allergy.
Evaluation of Prostate-Specific Membrane Antigen (PSMA) Immunohistochemical Expression in Early-Stage Breast Cancer Subtypes
Authors: Andryszak Natalia , Kurzawa Paweł , Krzyżaniak Monika , Nowicki Michał , Ruchała Marek , Iżycki Dariusz , Czepczyński Rafał
Published: June 2024

Breast cancer, known for its diverse subtypes, ranks as one of the leading causes of cancer-related deaths. Prostate-specific membrane antigen (PSMA), primarily associated with prostate cancer, has also been identified in breast cancer, though its role remains unclear. This study aimed to evaluate PSMA expression across different subtypes of early-stage breast cancer and investigate its correlation with clinicopathological factors. This retrospective study included 98 breast cancer cases. PSMA expression was examined in both tumor cells and tumor-associated blood vessels. The analysis revealed PSMA expression in tumor-associated blood vessels in 88 cases and in tumor cells in 75 cases. Ki67 expression correlated positively with PSMA expression in blood vessels (p < 0.0001, RSpearman 0.42) and tumor cells (p = 0.010, RSpearman 0.26). The estrogen and progesterone receptor expression correlated negatively with PSMA levels in blood vessels (p = 0.0053, R Spearman −0.26 and p = 0.00026, R Spearman −0.347, respectively). Human epidermal growth factor receptor 2 (HER2) status did not significantly impact PSMA expression. We did not detect any statistically significant differences between breast cancer subtypes. These findings provide evidence for a heterogenous PSMA expression in breast cancer tissue and suggest its correlation with tumor aggressiveness. Despite the limited sample size, the study provides valuable insights into the potential of PSMA as a prognostic, diagnostic, and therapeutic target in the management of breast cancer.
Glutamate-Mediated Excitotoxicity in the Pathogenesis and Treatment of Neurodevelopmental and Adult Mental Disorders
Authors: Nicosia Noemi , Giovenzana Mattia , Misztak Paulina , Mingardi Jessica , Musazzi Laura
Published: June 2024

Glutamate is the main excitatory neurotransmitter in the brain wherein it controls cognitive functional domains and mood. Indeed, brain areas involved in memory formation and consolidation as well as in fear and emotional processing, such as the hippocampus, prefrontal cortex, and amygdala, are predominantly glutamatergic. To ensure the physiological activity of the brain, glutamatergic transmission is finely tuned at synaptic sites. Disruption of the mechanisms responsible for glutamate homeostasis may result in the accumulation of excessive glutamate levels, which in turn leads to increased calcium levels, mitochondrial abnormalities, oxidative stress, and eventually cell atrophy and death. This condition is known as glutamate-induced excitotoxicity and is considered as a pathogenic mechanism in several diseases of the central nervous system, including neurodevelopmental, substance abuse, and psychiatric disorders. On the other hand, these disorders share neuroplasticity impairments in glutamatergic brain areas, which are accompanied by structural remodeling of glutamatergic neurons. In the current narrative review, we will summarize the role of glutamate-induced excitotoxicity in both the pathophysiology and therapeutic interventions of neurodevelopmental and adult mental diseases with a focus on autism spectrum disorders, substance abuse, and psychiatric disorders. Indeed, glutamatergic drugs are under preclinical and clinical development for the treatment of different mental diseases that share glutamatergic neuroplasticity dysfunctions. Although clinical evidence is still limited and more studies are required, the regulation of glutamate homeostasis is attracting attention as a potential crucial target for the control of brain diseases.
Human Brain In Vitro Model for Pathogen Infection-Related Neurodegeneration Study
Authors: Yan Yuwei , Cho Ann-Na
Published: June 2024

Recent advancements in stem cell biology and tissue engineering have revolutionized the field of neurodegeneration research by enabling the development of sophisticated in vitro human brain models. These models, including 2D monolayer cultures, 3D organoids, organ-on-chips, and bioengineered 3D tissue models, aim to recapitulate the cellular diversity, structural organization, and functional properties of the native human brain. This review highlights how these in vitro brain models have been used to investigate the effects of various pathogens, including viruses, bacteria, fungi, and parasites infection, particularly in the human brain cand their subsequent impacts on neurodegenerative diseases. Traditional studies have demonstrated the susceptibility of different 2D brain cell types to infection, elucidated the mechanisms underlying pathogen-induced neuroinflammation, and identified potential therapeutic targets. Therefore, current methodological improvement brought the technology of 3D models to overcome the challenges of 2D cells, such as the limited cellular diversity, incomplete microenvironment, and lack of morphological structures by highlighting the need for further technological advancements. This review underscored the significance of in vitro human brain cell from 2D monolayer to bioengineered 3D tissue model for elucidating the intricate dynamics for pathogen infection modeling. These in vitro human brain cell enabled researchers to unravel human specific mechanisms underlying various pathogen infections such as SARS-CoV-2 to alter blood-brain-barrier function and Toxoplasma gondii impacting neural cell morphology and its function. Ultimately, these in vitro human brain models hold promise as personalized platforms for development of drug compound, gene therapy, and vaccine. Overall, we discussed the recent progress in in vitro human brain models, their applications in studying pathogen infection-related neurodegeneration, and future directions.
A Glimpse into Humoral Response and Related Therapeutic Approaches of Takayasu’s Arteritis
Authors: Guo Shuning , Tian Yixiao , Li Jing , Zeng Xiaofeng
Published: June 2024

Takayasu’s arteritis (TAK) manifests as an insidiously progressive and debilitating form of granulomatous inflammation including the aorta and its major branches. The precise etiology of TAK remains elusive, with current understanding suggesting an autoimmune origin primarily driven by T cells. Notably, a growing body of evidence bears testimony to the widespread effects of B cells on disease pathogenesis and progression. Distinct alterations in peripheral B cell subsets have been described in individuals with TAK. Advancements in technology have facilitated the identification of novel autoantibodies in TAK. Moreover, emerging data suggest that dysregulated signaling cascades downstream of B cell receptor families, including interactions with innate pattern recognition receptors such as toll-like receptors, as well as co-stimulatory molecules like CD40, CD80 and CD86, may result in the selection and proliferation of autoreactive B cell clones in TAK. Additionally, ectopic lymphoid neogenesis within the aortic wall of TAK patients exhibits functional characteristics. In recent decades, therapeutic interventions targeting B cells, notably utilizing the anti-CD20 monoclonal antibody rituximab, have demonstrated efficacy in TAK. Despite the importance of the humoral immune response, a systematic understanding of how autoreactive B cells contribute to the pathogenic process is still lacking. This review provides a comprehensive overview of the biological significance of B cell-mediated autoimmunity in TAK pathogenesis, as well as insights into therapeutic strategies targeting the humoral response. Furthermore, it examines the roles of T-helper and T follicular helper cells in humoral immunity and their potential contributions to disease mechanisms. We believe that further identification of the pathogenic role of autoimmune B cells and the underlying regulation system will lead to deeper personalized management of TAK patients. We believe that further elucidation of the pathogenic role of autoimmune B cells and the underlying regulatory mechanisms holds promise for the development of personalized approaches to managing TAK patients.