bluuebunny/crossref_metadata_2025 huggingface dataset:
Children’s Influence on Their Parents’ Satisfaction with Physical Activity in Nature: An Exploratory Study
Authors: Rojo-Ramos Jorge , Castillo-Paredes Antonio , Mendoza-Muñoz María , Adsuar José Carmelo , Polo-Campos Irene , Gomez-Paniagua Santiago , Galán-Arroyo Carmen
Published: March 2023

Physical activity in nature has several benefits as it is important for good health, offering physical, social, psychological or even ecological benefits. Nevertheless, in order to maintain adherence to this practice, high levels of satisfaction with the practice are necessary. The objective of this study is to explore whether children’s characteristics influence parental satisfaction with physical activity in nature, analyzing possible differences according to the gender and age of their children. Two hundred and eighty parents responded to two sociodemographic questions in addition to the Physical Activity Enjoyment Scale (PACES), which consists of 16 items. The normality of the data was determined using the Kolmogorov-Smirnov test. Subsequently, nonparametric tests were used to analyze the variables of gender and age in the items, dimensions and total scores of the questionnaire. Statistical differences were found in some of the positive items, which varied according to the age of the children. However, no significant differences were found in the items with respect to the children’s gender or when examining the dimensions or total score of the questionnaire based on both variables. Likewise, age did not show significant correlations with the dimensions and the total score of the questionnaire. Consequently, this study indicates that a child’s age may influence parents’ positive perceptions of the enjoyment of physical activity in nature. Similarly, the gender of the child does not seem to influence these perceptions.
The Global Deterioration Scale for Down Syndrome Population (GDS-DS): A Rating Scale to Assess the Progression of Alzheimer’s Disease
Authors: Rodríguez-Hidalgo Emili , García-Alba Javier , Novell Ramon , Esteba-Castillo Susanna
Published: March 2023

The aim of this study is to adapt and validate the global deterioration scale (GDS) for the systematic tracking of Alzheimer’s disease (AD) progression in a population with Down syndrome (DS). A retrospective dual-center cohort study was conducted with 83 participants with DS (46.65 ± 5.08 years) who formed the primary diagnosis (PD) group: cognitive stability (n = 48), mild cognitive impairment (n = 24), and Alzheimer’s disease (n = 11). The proposed scale for adults with DS (GDS-DS) comprises six stages, from cognitive and/or behavioral stability to advanced AD. Two neuropsychologists placed the participants of the PD group in each stage of the GDS-DS according to cognitive, behavioral and daily living skills data. Inter-rater reliability in staging with the GDS-DS was excellent (ICC = 0.86; CI: 0.80–0.93), and the agreement with the diagnosis categories of the PD group ranged from substantial to excellent with κ values of 0.82 (95% CI: 0.73–0.92) and 0.85 (95% CI: 0.72, 0.99). Performance with regard to the CAMCOG-DS total score and orientation subtest of the Barcelona test for intellectual disability showed a slight progressive decline across all the GDS-DS stages. The GDS-DS scale is a sensitive tool for staging the progression of AD in the DS population, with special relevance in daily clinical practice.
Overweight in Older Adults: A Follow-Up of Fifteen Years of the SABE Survey
Authors: de Araujo Tânia Aparecida , Oliveira Isabela Martins , Silva Tarsila Guimarães Vieira da , da Silva Vanderlei Carneiro , Duarte Yeda Aparecida de Oliveira
Published: March 2023

Despite extensive research on overweight and obesity, there are few studies that present longitudinal statistical analyses among non-institutionalized older adults, particularly in low- and middle-income countries. This study aimed to assess the prevalence and factors associated with excess weight in older adults from the same cohort over a period of fifteen years. A total of 264 subjects aged (≥60 years) from the SABE survey (Health, Wellbeing and Aging) in the years 2000, 2006, 2010, and 2015 in the city of São Paulo, Brazil, were evaluated. Overweight was assessed by a BMI of ≥28 kg/m2. Multinomial logistic regression models adjusted for sociodemographic and health data were used to assess factors associated with excess weight. After normal weight, overweight was the most prevalent nutritional status in all evaluated periods: 34.02% in 2000 (95%CI: 28.29–40.26); 34.86% in 2006 (95%CI: 28.77–41.49%); 41.38% in 2010 (95%CI: 35.25–47.79); 33.75% in 2015 (95%CI: 28.02–40.01). Being male was negatively associated with being overweight in all years (OR: 0.34 in 2000; OR: 0.36 in 2006; OR: 0.27 in 2010; and OR: 0.43 in 2015). A greater number of chronic diseases and worse functionality were the main factors associated with overweight, regardless of gender, age, marital status, education, physical activity, and alcohol or tobacco consumption. Older adults with overweight and obesity, a greater number of chronic diseases, and difficulties in carrying out daily tasks required a greater commitment to healthcare. Health services must be prepared to accommodate this rapidly growing population in low- and middle-income countries.
Levels, Distributions, and Potential Risks of Hexachlorobutadiene from Two Tetrachloroethylene Factories in China
Authors: Liu Chengyou , Guo Jing , Liu Meng , Liu Jinlin , Zhang Lifei
Published: March 2023

A systematic investigation was conducted on the emission of hexachlorobutadiene (HCBD) from two tetrachloroethylene factories that used the acetylene method (F1) and the tetrachloride transformation method (F2). The levels of HCBD in the air for F1 were found to be in the range of 1.46–1170 µg/m3, whereas F2 had levels in the range of 1.96–5530 µg/m3. Similarly, the levels of HCBD in the soil for F1 were found to be in the range from 42.2 to 140 µg/kg, whereas F2 had levels in the range from 4.13 to 2180 µg/kg. Samples obtained from the air, soil, and sludge in the reaction area of the tetrachloroethylene factories in China showed high levels of HCBD. The F1 method unintentionally produced more HCBD than the F2 method during tetrachloroethylene production, leading to greater harm. The results of the risk assessment suggested the presence of harmful health effects on workers in the workplace. The investigation findings highlight the need for improved management systems to ensure the safe production of tetrachloroethylene.
Integrating Environmental Data with Medical Data in a Records-Linkage System to Explore Groundwater Nitrogen Levels and Child Health Outcomes
Authors: Prissel Christine M. , Grossardt Brandon R. , Klinger Gregory S. , St. Sauver Jennifer L. , Rocca Walter A.
Published: March 2023

Background: The Rochester Epidemiology Project (REP) medical records-linkage system offers a unique opportunity to integrate medical and residency data with existing environmental data, to estimate individual-level exposures. Our primary aim was to provide an archetype of this integration. Our secondary aim was to explore the association between groundwater inorganic nitrogen concentration and adverse child and adolescent health outcomes. Methods: We conducted a nested case-control study in children, aged seven to eighteen, from six counties of southeastern Minnesota. Groundwater inorganic nitrogen concentration data were interpolated, to estimate exposure across our study region. Residency data were then overlaid, to estimate individual-level exposure for our entire study population (n = 29,270). Clinical classification software sets of diagnostic codes were used to determine the presence of 21 clinical conditions. Regression models were adjusted for age, sex, race, and rurality. Results: The analyses support further investigation of associations between nitrogen concentration and chronic obstructive pulmonary disease and bronchiectasis (OR: 2.38, CI: 1.64–3.46) among boys and girls, thyroid disorders (OR: 1.44, CI: 1.05–1.99) and suicide and intentional self-inflicted injury (OR: 1.37, CI: >1.00–1.87) among girls, and attention deficit conduct and disruptive behavior disorders (OR: 1.34, CI: 1.24–1.46) among boys. Conclusions: Investigators with environmental health research questions should leverage the well-enumerated population and residency data in the REP.
Effect of Ceramic and Dentin Thicknesses and Type of Resin-Based Luting Agents on Intrapulpal Temperature Changes during Luting of Ceramic Inlays
Authors: Kincses Dóra , Jordáki Dóra , Szebeni Donát , Kunsági-Máté Sándor , Szalma József , Lempel Edina
Published: March 2023

The adhesive cementation of ceramic inlays may increase pulpal temperature (PT) and induce pulpal damage due to heat generated by the curing unit and the exothermic reaction of the luting agent (LA). The aim was to measure the PT rise during ceramic inlay cementation by testing different combinations of dentin and ceramic thicknesses and LAs. The PT changes were detected using a thermocouple sensor positioned in the pulp chamber of a mandibular molar. Gradual occlusal reduction obtained dentin thicknesses of 2.5, 2.0, 1.5, and 1.0 mm. Light-cured (LC) and dual-cured (DC) adhesive cements and preheated restorative resin-based composite (RBC) were applied to luting of 2.0, 2.5, 3.0, and 3.5 mm lithium disilicate ceramic blocks. Differential scanning calorimetry was used to compare the thermal conductivity of dentin and ceramic slices. Although ceramic reduced heat delivered by the curing unit, the exothermic reaction of the LAs significantly increased it in each investigated combination (5.4–7.9 °C). Temperature changes were predominantly influenced by dentin thickness followed by LA and ceramic thickness. Thermal conductivity of dentin was 24% lower than that of ceramic, and its thermal capacity was 86% higher. Regardless of the ceramic thickness, adhesive inlay cementation can significantly increase the PT, especially when the remaining dentin thickness is <2 mm.
Cold Storage Followed by Transplantation Induces Interferon-Gamma and STAT-1 in Kidney Grafts
Authors: McGraw Madison , Miller David , Lo Sorena , Parajuli Nirmala
Published: March 2023

Cold storage (CS)-mediated inflammation, a reality of donor kidney processing and transplantation, can contribute to organ graft failure. However, the mechanisms by which this inflammation is perpetuated during and after CS remain unclear. Here, we examined the immunoregulatory roles of signal transducer and activator of transcription (STAT) family proteins, most notably STAT1 and STAT3, with our in vivo model of renal CS and transplant. Donor rat kidneys were exposed to 4 h or 18 h of CS, which was then followed by transplantation (CS + transplant). STAT total protein level and activity (phosphorylation) were evaluated via Western blot analysis and mRNA expression was tabulated using quantitative RT-PCR after organ harvest on day 1 or day 9 post-surgery. In vivo assays were further corroborated via similar analyses featuring in vitro models, specifically proximal tubular cells (human and rat) as well as macrophage cells (Raw 264.7). Strikingly, gene expression of IFN-γ (a pro-inflammatory cytokine inducer of STAT) and STAT1 were markedly increased after CS + transplant. STAT3 dephosphorylation was additionally observed after CS, a result suggestive of dysregulation of anti-inflammatory signaling as phosphorylated STAT3 acts as a transcription factor in the nucleus to increase the expression of anti-inflammatory signaling molecules. In vitro, IFN-γ gene expression as well as amplification of downstream STAT1 and inducible nitric oxide synthase (iNOS; a hallmark of ischemia reperfusion injury) was remarkably increased after CS + rewarming. Collectively, these results demonstrate that aberrant induction of STAT1 is sustained in vivo post-CS exposure and post-transplant. Thus, Jak/STAT signaling may be a viable therapeutic target during CS to mitigate poor graft outcomes when transplanting kidneys from deceased donors.
An Insight into the Essential Role of Carbohydrate-Binding Modules in Enzymolysis of Xanthan
Authors: Ni Xin , Fu Tong , Wang Xueyan , Zhao Jingjing , Yu Zhimin , Li Xianzhen , Yang Fan
Published: March 2023

To date, due to the low accessibility of enzymes to xanthan substrates, the enzymolysis of xanthan remains deficient, which hinders the industrial production of functional oligoxanthan. To enhance the enzymatic affinity against xanthan, the essential role of two carbohydrate binding modules—MiCBMx and PspCBM84, respectively, derived from Microbacterium sp. XT11 and Paenibacillus sp. 62047—in catalytic properties of endotype xanthanase MiXen were investigated for the first time. Basic characterizations and kinetic parameters of different recombinants revealed that, compared with MiCBMx, PspCBM84 dramatically increased the thermostability of endotype xanthanase, and endowed the enzyme with higher substrate affinity and catalytic efficiency. Notably, the activity of endotype xanthanase was increased by 16 times after being fused with PspCBM84. In addition, the presence of both CBMs obviously enabled endotype xanthanase to produce more oligoxanthan, and xanthan digests prepared by MiXen-CBM84 showed better antioxidant activity due to the higher content of active oligosaccharides. The results of this work lay a foundation for the rational design of endotype xanthanase and the industrial production of oligoxanthan in the future.
Molecular Mechanism of Action of Neonicotinoid Insecticides
Authors: Thany Steeve H.
Published: March 2023

Since neonicotinoid insecticides were first introduced several years ago, most of them have been banned by the European Union due to their potentially adverse effects on humans and useful insects [...]
Characterization and Proteomic Analysis of Plasma EVs Recovered from Healthy and Diseased Dogs with Canine Leishmaniosis
Authors: Esteves Sofia , Lima Clara , Costa Inês , Osório Hugo , Fernandez-Becerra Carmen , Santarém Nuno , Cordeiro-da-Silva Anabela
Published: March 2023

Dogs are highly valued companions and work animals that are susceptible to many life-threatening conditions such as canine leishmaniosis (CanL). Plasma-derived extracellular vesicles (EVs), exploited extensively in biomarker discovery, constitute a mostly untapped resource in veterinary sciences. Thus, the definition of proteins associated with plasma EVs recovered from healthy and diseased dogs with a relevant pathogen would be important for biomarker development. For this, we recovered, using size-exclusion chromatography (SEC), EVs from 19 healthy and 20 CanL dogs’ plasma and performed proteomic analysis by LC-MS/MS to define their core proteomic composition and search for CanL-associated alterations. EVs-specific markers were identified in all preparations and also non-EVs proteins. Some EVs markers such as CD82 were specific to the healthy animals, while others, such as the Integrin beta 3 were identified in most samples. The EVs-enriched preparations allowed the identification of 529 canine proteins that were identified in both groups, while 465 and 154 were only identified in healthy or CanL samples, respectively. A GO enrichment analysis revealed few CanL-specific terms. Leishmania spp. protein identifications were also found, although with only one unique peptide. Ultimately, CanL-associated proteins of interest were identified and a core proteome was revealed that will be available for intra- and inter-species comparisons.
Antimicrobial Resistance and Genomic Characterization of Salmonella Infantis from Different Sources
Authors: Montone Angela Michela Immacolata , Cutarelli Anna , Peruzy Maria Francesca , La Tela Immacolata , Brunetti Roberta , Pirofalo Maria Gerarda , Folliero Veronica , Balestrieri Anna , Murru Nicoletta , Capuano Federico
Published: March 2023

The epidemiology of Salmonella Infantis is complex in terms of its distribution and transmission. The continuous collection and analysis of updated data on the prevalence and antimicrobic resistance are essential. The present work aimed to investigate the antimicrobial resistance and the correlation among S. Infantis isolates from different sources through the multiple-locus variable-number of tandem repeat (VNTR) analysis (MLVA). A total of 562 Salmonella strains isolated from 2018 to 2020 from poultry, humans, swine, water buffalo, mussels, cattle, and wild boar were serotyped, and 185 S. Infantis strains (32.92%) were identified. S. Infantis was commonly isolated in poultry and, to a lesser extent, in other sources. The isolates were tested against 12 antimicrobials, and a high prevalence of resistant strains was recorded. S. Infantis showed high resistance against fluoroquinolones, ampicillin, and tetracycline, which are commonly used in human and veterinary medicine. From all S. Infantis isolates, five VNTR loci were amplified. The use of MLVA was not sufficient to understand the complexity of the epidemiological relationships between S. Infantis strains. In conclusion, an alternative methodology to investigate genetic similarities and differences among S. Infantis strains is needed.
Claudin-4: A New Molecular Target for Epithelial Cancer Therapy
Authors: Fujiwara-Tani Rina , Mori Shiori , Ogata Ruiko , Sasaki Rika , Ikemoto Ayaka , Kishi Shingo , Kondoh Masuo , Kuniyasu Hiroki
Published: March 2023

Claudin-4 (CLDN4) is a key component of tight junctions (TJs) in epithelial cells. CLDN4 is overexpressed in many epithelial malignancies and correlates with cancer progression. Changes in CLDN4 expression have been associated with epigenetic factors (such as hypomethylation of promoter DNA), inflammation associated with infection and cytokines, and growth factor signaling. CLDN4 helps to maintain the tumor microenvironment by forming TJs and acts as a barrier to the entry of anticancer drugs into tumors. Decreased expression of CLDN4 is a potential marker of epithelial-mesenchymal transition (EMT), and decreased epithelial differentiation due to reduced CLDN4 activity is involved in EMT induction. Non-TJ CLDN4 also activates integrin beta 1 and YAP to promote proliferation, EMT, and stemness. These roles in cancer have led to investigations of molecular therapies targeting CLDN4 using anti-CLDN4 extracellular domain antibodies, gene knockdown, clostridium perfringens enterotoxin (CPE), and C-terminus domain of CPE (C-CPE), which have demonstrated the experimental efficacy of this approach. CLDN4 is strongly involved in promoting malignant phenotypes in many epithelial cancers and is regarded as a promising molecular therapeutic target.
Amphiphilic Polyethylene-b-poly(L-lysine) Block Copolymer: Synthesis, Self-Assembly, and Responsivity
Authors: Pei Lixia , Ma Hongyu , Jiang Yan , Zheng Handou , Gao Haiyang
Published: March 2023

Polyethylene-b-polypeptide copolymers are biologically interesting, but studies of their synthesis and properties are very few. This paper reports synthesis and characterization of well-defined amphiphilic polyethylene-block-poly(L-lysine) (PE-b-PLL) block copolymers by combining nickel-catalyzed living ethylene polymerization with controlled ring-opening polymerization (ROP) of ε-benzyloxycarbonyl-L-lysine-N-carboxyanhydride (Z-Lys-NCA) and sequential post-functionalization. Amphiphilic PE-b-PLL block copolymers self-assembled into spherical micelles with a hydrophobic PE core in aqueous solution. The pH and ionic responsivities of PE-b-PLL polymeric micelles were investigated by means of fluorescence spectroscopy, dynamic light scattering, UV-circular dichroism, and transmission electron microscopy. The variation of pH values led to the conformational alteration of PLL from α-helix to coil, thereby changing the micelle dimensions.
Characterization of tRNA-Derived Fragments in Lung Squamous Cell Carcinoma with Respect to Tobacco Smoke
Authors: Magesh Shruti , Gande Pranava , Yalamarty Rishabh , John Daniel , Chakladar Jaideep , Li Wei Tse , Ongkeko Weg M.
Published: March 2023

Lung squamous cell carcinoma (LUSC) is a highly heterogeneous cancer that is influenced by etiological agents such as tobacco smoke. Accordingly, transfer RNA-derived fragments (tRFs) are implicated in both cancer onset and development and demonstrate the potential to act as targets for cancer treatments and therapies. Therefore, we aimed to characterize tRF expression with respect to LUSC pathogenesis and clinical outcomes. Specifically, we analyzed the effect of tobacco smoke on tRF expression. In order to do so, we extracted tRF read counts from MINTbase v2.0 for 425 primary tumor samples and 36 adjacent normal samples. We analyzed the data in three primary cohorts: (1) all primary tumor samples (425 samples), (2) smoking-induced LUSC primary tumor samples (134 samples), and (3) non-smoking-induced LUSC primary tumor samples (18 samples). Differential expression analysis was performed to examine tRF expression in each of the three cohorts. tRF expression was correlated to clinical variables and patient survival outcomes. We identified unique tRFs in primary tumor samples, smoking-induced LUSC primary tumor samples, and non-smoking-induced LUSC primary tumor samples. In addition, many of these tRFs demonstrated correlations to worse patient survival outcomes. Notably, tRFs in the smoking-induced LUSC and non-smoking-induced LUSC primary tumor cohorts were significantly correlated to clinical variables pertaining to cancer stage and treatment efficacy. We hope that our results will be used to better inform future LUSC diagnostic and therapeutic modalities.
Influence of Lipidation Pattern of the KR12 Fragment of Peptide LL-37 on Its Antibacterial and Hemolytic Activities
Authors: Kamysz Elżbieta , Sikorska Emilia , Bauer Marta , Sikora Karol , Neubauer Damian
Published: March 2023

Contemporary medicine has been confronted by multidrug resistance. Therefore, new antibiotics are sought to alleviate the problem. In this study, we estimated the effect of the positioning and extent of lipidation (mainly octanoic acid residue) in the KR12-NH2 molecule on antibacterial and hemolytic activities. The effect of the conjugation of benzoic acid derivatives (C6H5-X-COOH, where X: CH2, CH2-CH2, CH=CH, C≡C, and CH2-CH2-CH2) with the N-terminal part of KR12-NH2 on biological activity was also studied. All analogs were tested against planktonic cells of ESKAPE bacteria and reference strains of Staphylococcus aureus. The effect of lipidation site on the helicity of the KR12-NH2 analogs was studied using CD spectroscopy. The ability of the selected peptides to induce the aggregation of POPG liposomes was evaluated with DLS measurements. We demonstrated that both the site and extent of peptide lipidation play an essential role in the bacterial specificity of the lipopeptides. Most of the C8α-KR12-NH2 (II) analogs that were more hydrophobic than the parent compound were also more hemolytic. A similar relationship was also found between the α-helical structure content in POPC and hemolytic activity. It is worth emphasizing that in our study, the highest selectivity against S. aureus strains with an SI value of at least 21.11 exhibited peptide XII obtained by the conjugation of the octanoic acid with the N-terminus of retro-KR12-NH2. All lipidated analogs with the highest net charge (+5) were the most selective toward pathogens. Therefore, the overall charge of KR12-NH2 analogs plays pivotal role in their biological activity.
The Molecular Mechanism of Polyphenols in the Regulation of Ageing Hallmarks
Authors: Pereira Quélita Cristina , dos Santos Tanila Wood , Fortunato Isabela Monique , Ribeiro Marcelo Lima
Published: March 2023

Ageing is a complex process characterized mainly by a decline in the function of cells, tissues, and organs, resulting in an increased risk of mortality. This process involves several changes, described as hallmarks of ageing, which include genomic instability, telomere attrition, epigenetic changes, loss of proteostasis, dysregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell depletion, and altered intracellular communication. The determining role that environmental factors such as diet and lifestyle play on health, life expectancy, and susceptibility to diseases, including cancer and neurodegenerative diseases, is wellestablished. In view of the growing interest in the beneficial effects of phytochemicals in the prevention of chronic diseases, several studies have been conducted, and they strongly suggest that the intake of dietary polyphenols may bring numerous benefits due to their antioxidant and anti-inflammatory properties, and their intake has been associated with impaired ageing in humans. Polyphenol intake has been shown to be effective in ameliorating several age-related phenotypes, including oxidative stress, inflammatory processes, impaired proteostasis, and cellular senescence, among other features, which contribute to an increased risk of ageing-associated diseases. This review aims to address, in a general way, the main findings described in the literature about the benefits of polyphenols in each of the hallmarks of ageing, as well as the main regulatory mechanisms responsible for the observed antiageing effects.
Salt-Affected Rocket Plants as a Possible Source of Glucosinolates
Authors: Corti Emilio , Falsini Sara , Gonnelli Cristina , Pieraccini Giuseppe , Nako Besiana , Papini Alessio
Published: March 2023

Soil salinity can have various negative consequences on agricultural products, from their quality and production to their aesthetic traits. In this work, the possibility to use salt-affected vegetables, that otherwise would be discarded, as a source of nutraceuticals was explored. To this aim, rocket plants, a vegetable featuring bioactive compounds such as glucosinolates, were exposed to increasing NaCl concentrations in hydroponics and analysed for their content in bioactive compounds. Salt levels higher than 68 mM produced rocket plants that did not comply with European Union regulations and would therefore be considered a waste product. Anyway, our findings, obtained by Liquid Chromatography-High Resolution Mass Spectrometry, demonstrated a significant increase in glucosinolates levels in such salt-affected plants. opening the opportunity for a second life of these market discarded products to be recycled as glucosinolates source. Furthermore, an optimal situation was found at NaCl 34 mM in which not only were the aesthetic traits of rocket plants not affected, but also the plants revealed a significant enrichment in glucosinolates. This can be considered an advantageous situation in which the resulting vegetables still appealed to the market and showed improved nutraceutical aspects.
Intracellular Conformation of Amyotrophic Lateral Sclerosis-Causative TDP-43
Authors: Kitamura Akira , Yuno Sachiko , Kawamura Rintaro , Kinjo Masataka
Published: March 2023

Transactive response element DNA/RNA-binding protein 43 kDa (TDP-43) is the causative protein of amyotrophic lateral sclerosis (ALS); several ALS-associated mutants of TDP-43 have been identified. TDP-43 has several domains: an N-terminal domain, two RNA/DNA-recognition motifs, and a C-terminal intrinsically disordered region (IDR). Its structures have been partially determined, but the whole structure remains elusive. In this study, we investigate the possible end-to-end distance between the N- and C-termini of TDP-43, its alterations due to ALS-associated mutations in the IDR, and its apparent molecular shape in live cells using Förster resonance energy transfer (FRET) and fluorescence correlation spectroscopy (FCS). Furthermore, the interaction between ALS-associated TDP-43 and heteronuclear ribonucleoprotein A1 (hnRNP A1) is slightly stronger than that of wild-type TDP-43. Our findings provide insights into the structure of wild-type and ALS-associated mutants of TDP-43 in a cell.
Mitochondrial Dysfunction in Intensive Care Unit-Acquired Weakness and Critical Illness Myopathy: A Narrative Review
Authors: Klawitter Felix , Ehler Johannes , Bajorat Rika , Patejdl Robert
Published: March 2023

Mitochondria are key structures providing most of the energy needed to maintain homeostasis. They are the main source of adenosine triphosphate (ATP), participate in glucose, lipid and amino acid metabolism, store calcium and are integral components in various intracellular signaling cascades. However, due to their crucial role in cellular integrity, mitochondrial damage and dysregulation in the context of critical illness can severely impair organ function, leading to energetic crisis and organ failure. Skeletal muscle tissue is rich in mitochondria and, therefore, particularly vulnerable to mitochondrial dysfunction. Intensive care unit-acquired weakness (ICUAW) and critical illness myopathy (CIM) are phenomena of generalized weakness and atrophying skeletal muscle wasting, including preferential myosin breakdown in critical illness, which has also been linked to mitochondrial failure. Hence, imbalanced mitochondrial dynamics, dysregulation of the respiratory chain complexes, alterations in gene expression, disturbed signal transduction as well as impaired nutrient utilization have been proposed as underlying mechanisms. This narrative review aims to highlight the current known molecular mechanisms immanent in mitochondrial dysfunction of patients suffering from ICUAW and CIM, as well as to discuss possible implications for muscle phenotype, function and therapeutic approaches.
Circulating Extracellular Vesicles microRNAs Are Altered in Women Undergoing Preterm Birth
Authors: Ramos Bruna Ribeiro Andrade , Tronco Júlia Abbade , Carvalho Márcio , Felix Tainara Francini , Reis Patrícia Pintor , Silveira Juliano Coelho , Silva Márcia Guimarães
Published: March 2023

Preterm labor (PTL) and preterm premature rupture of membranes (PPROM) lead to high perinatal morbidity/mortality rates worldwide. Small extracellular vesicles (sEV) act in cell communication and contain microRNAs that may contribute to the pathogenesis of these complications. We aimed to compare the expression, in sEV from peripheral blood, of miRNAs between term and preterm pregnancies. This cross-sectional study included women who underwent PTL, PPROM, and term pregnancies, examined at the Botucatu Medical School Hospital, SP, Brazil. sEV were isolated from plasma. Western blot used to detect exosomal protein CD63 and nanoparticle tracking analysis were performed. The expression of 800 miRNAs was assessed by the nCounter Humanv3 miRNA Assay (NanoString). The miRNA expression and relative risk were determined. Samples from 31 women—15 preterm and 16 term—were included. miR-612 expression was increased in the preterm groups. miR-612 has been shown to increase apoptosis in tumor cells and to regulate the nuclear factor κB inflammatory pathway, processes involved in PTL/PPROM pathogenesis. miR-1253, miR-1283, miR378e, and miR-579-3p, all associated with cellular senescence, were downregulated in PPROM compared with term pregnancies. We conclude that miRNAs from circulating sEV are differentially expressed between term and preterm pregnancies and modulate genes in pathways that are relevant to PTL/PPROM pathogenesis.
Heart-Type Fatty Acid Binding Protein Binds Long-Chain Acylcarnitines and Protects against Lipotoxicity
Authors: Zelencova-Gopejenko Diana , Videja Melita , Grandane Aiga , Pudnika-Okinčica Linda , Sipola Anda , Vilks Karlis , Dambrova Maija , Jaudzems Kristaps , Liepinsh Edgars
Published: March 2023

Heart-type fatty-acid binding protein (FABP3) is an essential cytosolic lipid transport protein found in cardiomyocytes. FABP3 binds fatty acids (FAs) reversibly and with high affinity. Acylcarnitines (ACs) are an esterified form of FAs that play an important role in cellular energy metabolism. However, an increased concentration of ACs can exert detrimental effects on cardiac mitochondria and lead to severe cardiac damage. In the present study, we evaluated the ability of FABP3 to bind long-chain ACs (LCACs) and protect cells from their harmful effects. We characterized the novel binding mechanism between FABP3 and LCACs by a cytotoxicity assay, nuclear magnetic resonance, and isothermal titration calorimetry. Our data demonstrate that FABP3 is capable of binding both FAs and LCACs as well as decreasing the cytotoxicity of LCACs. Our findings reveal that LCACs and FAs compete for the binding site of FABP3. Thus, the protective mechanism of FABP3 is found to be concentration dependent.
Attenuation of Ventilation-Enhanced Epithelial–Mesenchymal Transition through the Phosphoinositide 3-Kinase-γ in a Murine Bleomycin-Induced Acute Lung Injury Model
Authors: Li Li-Fu , Yu Chung-Chieh , Huang Chih-Yu , Wu Huang-Pin , Chu Chien-Ming , Liu Ping-Chi , Liu Yung-Yang
Published: March 2023

Mechanical ventilation (MV) used in patients with acute lung injury (ALI) induces lung inflammation and causes fibroblast proliferation and excessive collagen deposition—a process termed epithelial–mesenchymal transition (EMT). Phosphoinositide 3-kinase-γ (PI3K-γ) is crucial in modulating EMT during the reparative phase of ALI; however, the mechanisms regulating the interactions among MV, EMT, and PI3K-γ remain unclear. We hypothesized that MV with or without bleomycin treatment would increase EMT through the PI3K-γ pathway. C57BL/6 mice, either wild-type or PI3K-γ-deficient, were exposed to 6 or 30 mL/kg MV for 5 h after receiving 5 mg/kg AS605240 intraperitoneally 5 days after bleomycin administration. We found that, after bleomycin exposure in wild-type mice, high-tidal-volume MV induced substantial increases in inflammatory cytokine production, oxidative loads, Masson’s trichrome staining level, positive staining of α-smooth muscle actin, PI3K-γ expression, and bronchial epithelial apoptosis (p < 0.05). Decreased respiratory function, antioxidants, and staining of the epithelial marker Zonula occludens-1 were also observed (p < 0.05). MV-augmented bleomycin-induced pulmonary fibrogenesis and epithelial apoptosis were attenuated in PI3K-γ-deficient mice, and we found pharmacological inhibition of PI3K-γ activity through AS605240 (p < 0.05). Our data suggest that MV augmented EMT after bleomycin-induced ALI, partially through the PI3K-γ pathway. Therapy targeting PI3K-γ may ameliorate MV-associated EMT.
Transcriptomic Differentiation of Phenotypes in Chronic Rhinosinusitis and Its Implications for Understanding the Underlying Mechanisms
Authors: Urbančič Jure , Košak Soklič Tanja , Demšar Luzar Ajda , Hočevar Boltežar Irena , Korošec Peter , Rijavec Matija
Published: March 2023

Chronic rhinosinusitis (CRS) is a multifaceted disease with variable clinical courses and outcomes. We aimed to determine CRS-associated nasal-tissue transcriptome in clinically well-characterized and phenotyped individuals, to gain a novel insight into the biological pathways of the disease. RNA-sequencing of tissue samples of patients with CRS with polyps (CRSwNP), without polyps (CRSsNP), and controls were performed. Characterization of differently expressed genes (DEGs) and functional and pathway analysis was undertaken. We identified 782 common CRS-associated nasal-tissue DEGs, while 375 and 328 DEGs were CRSwNP- and CRSsNP-specific, respectively. Common key DEGs were found to be involved in dendritic cell maturation, the neuroinflammation pathway, and the inhibition of the matrix metalloproteinases. Distinct CRSwNP-specific DEGs were involved in NF-kβ canonical pathways, Toll-like receptor signaling, HIF1α regulation, and the Th2 pathway. CRSsNP involved the NFAT pathway and changes in the calcium pathway. Our findings offer new insights into the common and distinct molecular mechanisms underlying CRSwNP and CRSsNP, providing further understanding of the complex pathophysiology of the CRS, with future research directions for novel treatment strategies.
The Allergenic Activity of Blo t 2, a Blomia tropicalis IgE-Binding Molecule
Authors: Mondol Ernesto , Donado Karen , Regino Ronald , Hernandez Karen , Mercado Dilia , Mercado Ana Carolina , Benedetti Inés , Puerta Leonardo , Zakzuk Josefina , Caraballo Luis
Published: March 2023

Only few allergens derived from house dust mite (HDM) species have been evaluated in terms of their potential to induce allergic inflammation. In this study, we aimed to evaluate different aspects of the allergenicity and allergenic activity of Blo t 2, a Blomia tropicalis allergen. Blo t 2 was produced as a recombinant protein in Escherichia coli. Its allergenic activity was tested in humans by skin prick test and basophil activation assays, and in mice, by passive cutaneous anaphylaxis and a model of allergic airway inflammation. Sensitization rate to Blo t 2 (54.3%) was similar to that found to Blo t 21 (57.2%) and higher than to Der p 2 (37.5%). Most Blo t 2-sensitized patients showed a low intensity response (99.5%). Blo t 2 elicited CD203c upregulation and allergen induced skin inflammation. Additionally, immunized animals produced anti-Blo t 2 IgE antibodies and passive transfer of their serum to non-immunized animals induced skin inflammation after allergen exposure. Immunized animals developed bronchial hyperreactivity and a strong inflammatory lung reaction (eosinophils and neutrophils). These results confirm the allergenic activity of Blo t 2 and supports its clinical relevance.
The Protective Role of TREM2 in the Heterogenous Population of Macrophages during Post-Myocardial Infarction Inflammation
Authors: Kim Sang Hyun , Lee Kwan Yong , Chang Kiyuk
Published: March 2023

Advances in interventions after myocardial infarction (MI) have dramatically increased survival, but MI remains the leading cause of heart failure due to maladaptive ventricular remodeling following ischemic damage. Inflammation is crucial in both the initial response to ischemia and subsequent wound healing in the myocardium. To date, preclinical and clinical efforts have been made to elucidate the deleterious effects of immune cells contributing to ventricular remodeling and to identify therapeutic molecular targets. The conventional concept classifies macrophages or monocytes into dichotomous populations, while recent studies support their diverse subpopulations and spatiotemporal dynamicity. The single-cell and spatial transcriptomic landscapes of macrophages in infarcted hearts successfully revealed the heterogeneity of cell types and their subpopulations post-MI. Among them, subsets of Trem2hi macrophages were identified that were recruited to infarcted myocardial tissue in the subacute phase of MI. The upregulation of anti-inflammatory genes was observed in Trem2hi macrophages, and an in vivo injection of soluble Trem2 during the subacute phase of MI significantly improved myocardial function and the remodeling of infarcted mice hearts, suggesting the potential therapeutic role of Trem2 in LV remodeling. Further investigation of the reparative role of Trem2 in LV remodeling would provide novel therapeutic targets for MI.
Relationship between Dubas Bug (Ommatissus lybicus) Infestation and the Development of Fungal-Induced Leaf Spots in Date Palms (Phoenix dactylifera)
Authors: Al-Nabhani Salem S. , Velazhahan Rethinasamy , Hussain Shah , Al-Raqmi Suad , Al-Hashmi Maryam , Al-Sadi Abdullah M.
Published: March 2023

The dubas bug (Ommatissus lybicus) (Hemiptera: Tropiduchidae) is a serious pest in date palms in several date-producing countries, including Oman. Infestation results in a severe reduction in yield and a weakening of date palm growth. In addition, egg laying, which causes injuries to date palm leaves, results in the development of necrotic lesions on the leaves. This study aimed at investigating the role of fungi in the development of necrotic leaf spots following dubas bug infestation. Leaf samples developing leaf spot symptoms were collected from dubas-bug-infested leaves, as the leaf spot symptoms were not observed on the non-infested leaves. Isolation from date palm leaves collected from 52 different farms yielded 74 fungal isolates. Molecular identification of the isolates revealed that they belonged to 31 fungal species, 16 genera, and 10 families. Among the isolated fungi, there were five Alternaria species, four species each of Penicillium and Fusarium, three species each of Cladosporium and Phaeoacremonium, and two species each of Quambalaria and Trichoderma. Out of the thirty-one fungal species, nine were pathogenic on date palm leaves and induced varying levels of leaf spot symptoms. The pathogenic species were Alternaria destruens, Fusarium fujikuroi species complex, F. humuli, F. microconidium, Cladosporium pseudochalastosporoides, C. endophyticum, Quambalaria cyanescens, Phaeoacremonium krajdenii, and P. venezuelense, which were reported for the first time as leaf spot causal agents in date palms. The study provided novel information on the effect of dubas bug infestation in date palms on the development of fungal infection and associated leaf spot symptoms.
The Adult and Larva of a New Species of the Genus Dila (Coleoptera, Blaptinae, Blaptini) from Himalayas, with Molecular Phylogenetic Inferences of Related Genera of the Blaptini
Authors: Li Xiu-Min , Ji Baoyue , Tian Juan , Ren Guo-Dong
Published: March 2023

In this study, a new species of the genus Dila Fischer von Waldheim, 1844, D. ngaria Li and Ren sp. n., was described from the southwestern Himalayas. The adult and larva were associated using molecular phylogenetic analyses based on fragments of three mitochondrial and one nuclear gene fragment (COI, Cytb, 16S and 28S-D2). Additionally, a preliminary phylogenetic tree was reconstructed and discussed based on a molecular dataset with seven related genera and 24 species of the tribe Blaptini. Meanwhile, the monophyly of the subtribe Dilina and the taxonomic status of D. bomina Ren and Li, 2001 are discussed. This work provides new molecular data for phylogenetic studies on the tribe Blaptini in the future.
Fire Resistance of Phosphogypsum- and Hemp-Based Bio-Aggregate Composite with Variable Amount of Binder
Authors: Bumanis Girts , Andzs Martins , Sinka Maris , Bajare Diana
Published: March 2023

Bio-aggregate composites (BACs) are typically formed by binding plant origin aggregates using organic or inorganic binders. Composite boards are being manufactured from hemp shives and Portland cement or lime and such material is associated with the so-called “hempcrete”. To reach a low greenhouse gas emission rate, alternative binders must be considered. Gypsum binder releases a seven times lower amount of CO2 during production compared with Portland cement, while waste gypsum can be even more efficient. In this research, gypsum-based BACs were elaborated and tested. Phosphogypsum was evaluated as an alternative binder. The objective of the research was to evaluate the fire resistance of gypsum- and phosphogypsum-binder-based BAC. In this study, the amount of binder was varied and BACs with a density from 200 to 400 kg/m3 were tested. For the first time, commercial gypsum- and phosphogypsum-based hemp shive BAC fire performance was evaluated using a cone calorimeter. Results indicate that the role of gypsum content has a significant effect on the fire resistance. Time on ignition increased from 14 to 19 s and the heat release rate peak was reduced by 57%. Phosphogypsum binder, compared with commercial gypsum, showed a slight improvement of fire resistance as impurities with high water attraction are in the structure of PG.
Recoater-Induced Distortions and Build Failures in Selective Laser Melting of Thin-Walled Ti6Al4V Parts
Authors: Lu Xufei , Chiumenti Michele , Cervera Miguel , Slimani Mehdi , Gonzalez Iban
Published: March 2023

Additively manufactured thin-walled structures through selective laser melting (SLM) are of great interest in achieving carbon-neutral industrial manufacturing. However, residual stresses and warpages as well as recoater crashes often occur in SLM, leading to the build failure of parts, especially for large-scale and lightweight geometries. The challenge in this work consists of investigating how the recoater affects the warpage and (sometimes) causes the failure of different thin-walled Ti6Al4V parts (wall thickness of 1.0 mm). All these parts are printed on the same platform using a commercial SLM machine. After the loose powder removal and before the cutting operation, a 3D-scanner is used to obtain the actual warpage of each component. Next, an in-house coupled thermo-mechanical finite element model suitable for the numerical simulation of the SLM process is enhanced to consider the recoater effects. This numerical framework is calibrated to predict the thin-walled warpage as measured by the 3D-scanner. The combination of numerical predictions with experimental observations facilitates a comprehensive understanding of the mechanical behavior of different thin-walled components as well as the failure mechanism due to the recoater. The findings show that the use of a higher laser energy input causes larger residual stresses and warpage responsible for the recoater crashes. Finally, potential solutions to mitigate the warpage and the recoater crashes in the SLM of lightweight structures are assessed using the validated model.
Therapeutic Plasma Exchange for the Treatment of Hyperthyroidism: Approach to the Patient with Thyrotoxicosis or Antithyroid-Drugs Induced Agranulocytosis
Authors: Tizianel Irene , Sabbadin Chiara , Censi Simona , Clausi Cristina , Colpo Anna , Leahu Anca , Iacobone Maurizio , Mian Caterina , Scaroni Carla , Ceccato Filippo
Published: March 2023

Primary hyperthyroidism is an endocrine disorder characterized by excessive thyroid hormone synthesis and secretion by the thyroid gland. Clinical manifestations of hyperthyroidism can vary from subclinical to overt forms. In rare cases, hyperthyroidism may represent a clinical emergency, requiring admission to an intensive care unit due to an acute and severe exacerbation of thyrotoxicosis, known as a thyroid storm. First-line treatment of hyperthyroidism is almost always based on medical therapy (with thioamides, beta-adrenergic blocking agents, glucocorticoids), radioactive iodine or total thyroidectomy, tailored to the patient’s diagnosis. In cases of failure/intolerance/adverse events or contraindication to these therapies, as well as in life-threatening situations, including a thyroid storm, it is necessary to consider an alternative treatment with extracorporeal systems, such as therapeutic plasma exchange (TPE). This approach can promptly resolve severe conditions by removing circulating thyroid hormones. Here we described two different applications of TPE in clinical practice: the first case is an example of thyrotoxicosis due to amiodarone treatment, while the second one is an example of a severe adverse event to antithyroid drugs (agranulocytosis induced by methimazole).
The Association between Iron Deficiency and Renal Outcomes Is Modified by Sex and Anemia in Patients with Chronic Kidney Disease Stage 1–4
Authors: Yu Pei-Hua , Chao Yu-Lin , Kuo I-Ching , Niu Sheng-Wen , Chiu Yi-Wen , Chang Jer-Ming , Hung Chi-Chih
Published: March 2023

Iron deficiency is prevalent in women and patients with chronic kidney disease (CKD). Iron deficiency is not only related to anemia but contributes to adverse consequences for the kidney as well. Whether iron status is associated with renal outcomes after considering sex and anemia in patients with CKD stage 1–4 is unclear. Thus, we investigated the association of iron or iron saturation with renal outcomes in a CKD cohort. During a follow-up of 8.2 years, 781 (31.2%) patients met the composite renal outcome of renal replacement therapy and a 50% decline in renal function. In linear regression, iron was associated with sex, hemoglobin (Hb), and nutritional markers. In a fully adjusted Cox regression model, the male patients with normal iron had a significantly decreased risk of renal outcomes (hazard ratio (HR) 0.718; 95% confidence interval (CI) 0.579 to 0.889), but the female patients did not exhibit this association. The non-anemic patients (Hb ≥ 11 g/dL) had a decreased risk of renal outcomes (HR 0.715; 95% CI 0.568 to 0.898), but the anemic patients did not. In the sensitivity analysis, transferrin saturation (TSAT) showed similar results. When comparing iron and TSAT, both indicators showed similar prognostic values. In conclusion, iron deficiency, indicated by either iron or iron saturation, was associated with poor renal outcomes in the male or non-anemic patients with CKD stage 1–4.