bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in Serum Blood Parameters in Farmed Rainbow Trout (Oncorhynchus mykiss) Fed with Diets Supplemented with Waste Derived from Supercritical Fluid Extraction of Sweet Basil (Ocimum basilicum)
Authors: Pastorino Paolo , Bergagna Stefania , Vercelli Cristina , Pagliasso Giulia , Dellepiane Lucrezia , Renzi Monia , Barbero Raffaella , Re Giovanni , Elia Antonia Concetta , Dondo Alessandro , Barceló Damià , Prearo Marino
Published: April 2022

The antimicrobial and immunostimulant proprieties of aromatic plant extracts have been widely described, but their effects on serum blood biochemistry in fish have not. For this study, we assessed the changes in serum blood biochemical parameters in rainbow trout fed with a fish diet supplemented with a basil supercritical extract (F1-BEO). Our hypothesis was that treatment and time would be associated with changes in 10 serum blood biochemical parameters. F1-BEO was added to a commercial feed (0.5, 1, 2, 3% w/w). The fish were fed for 30 days, and the blood samples were collected at 2 time points (15 and 30 days). A two-way ANOVA showed a significant effect of treatment, time, and interaction treatment × time on creatinine, urea, total protein, albumin, magnesium, and phosphorus (p < 0.05), a significant effect of both time and interaction treatment × time on cholesterol (CHOL), glutamic oxaloacetic transaminase (GOT), and glutamic pyruvic transaminase (GPT) levels, and a significant effect of time on triglycerides (p < 0.05). While changes in several of the parameters were observed, the levels remained within the normal range for rainbow trout. Notably, after 30 days there was a significant decrease in CHOL in fish treated with 0.5% and 1% w/w F1-BEO (p < 0.05). The statistically non-significant increase in GOT and GPT in the fish fed with F1-BEO up to 3% w/w indicated a positive effect of basil on liver health. Our findings suggest a potential use for basil extracts (for example., F1-BEO) in fish feed to reduce antibiotic use and improve fish welfare.
Evaluation of Selected Quality Parameters of “Agristigna” Monovarietal Extra Virgin Olive Oil and Its Apple Vinegar-Based Dressing during Storage
Authors: Loizzo Monica R. , Sicari Vincenzo , Spizzirri Umile G. , Romeo Rosa , Tundis Rosa , Mincione Antonio , Nicoletta Fiore P. , Restuccia Donatella
Published: April 2022

This study aimed to investigate the quality parameters and the oxidative stability (180 days of storage) of a water–oil emulsion formulated with Calabrian (Italy) monovarietal Agristigna extra virgin olive oil and apple vinegar. The best extra virgin olive oil/apple vinegar ratio was found to be 85/15 (v/v) and lecithin (2% w/v) was the best additive to reach proper stability and viscosity over time. An increase of lightness parameters was evidenced in both products in a storage time-dependent manner. During storage, both oil and dressing showed a free acidity level beyond the accepted limit for extra virgin olive oil, whereas a slight increase of the peroxide value was observed only for Glasoil at the end of the observation time without affecting sensory attributes. A general decrease of phytochemicals was observed for extra virgin olive oil and Glasoil, with different reduction trends and degrees depending on the chemical class. A lower stability of Glasoil during shelf-life was confirmed by the worsening of the rheological features and by the polyunsaturated fatty acids reduction (up to −21.71%) with a corresponding increase of the monounsaturated fatty acids/polyunsaturated fatty acids ratio (about +25.69%).
Mitochondrial DNA Profiling by Fractal Lacunarity to Characterize the Senescent Phenotype as Normal Aging or Pathological Aging
Authors: Zaia Annamaria , Maponi Pierluigi
Published: April 2022

Biocomplexity, chaos, and fractality can explain the heterogeneity of aging individuals by regarding longevity as a “secondary product” of the evolution of a dynamic nonlinear system. Genetic-environmental interactions drive the individual senescent phenotype toward normal, pathological, or successful aging. Mitochondrial dysfunctions and mitochondrial DNA (mtDNA) mutations represent a possible mechanism shared by disease(s) and the aging process. This study aims to characterize the senescent phenotype and discriminate between normal (nA) and pathological (pA) aging by mtDNA mutation profiling. MtDNA sequences from hospitalized and non-hospitalized subjects (age-range: 65–89 years) were analyzed and compared to the revised Cambridge Reference Sequence (rCRS). Fractal properties of mtDNA sequences were displayed by chaos game representation (CGR) method, previously modified to deal with heteroplasmy. Fractal lacunarity analysis was applied to characterize the senescent phenotype on the basis of mtDNA sequence mutations. Lacunarity parameter β, from our hyperbola model function, was statistically different (p < 0.01) between the nA and pA groups. Parameter β cut-off value at 1.26 × 10−3 identifies 78% nA and 80% pA subjects. This also agrees with the presence of MT-CO gene variants, peculiar to nA (C9546m, 83%) and pA (T9900w, 80%) mtDNA, respectively. Fractal lacunarity can discriminate the senescent phenotype evolving as normal or pathological aging by individual mtDNA mutation profile.
Transcriptomic Analysis of Canine Osteosarcoma from a Precision Medicine Perspective Reveals Limitations of Differential Gene Expression Studies
Authors: Nance Rebecca L. , Cooper Sara J. , Starenki Dmytro , Wang Xu , Matz Brad , Lindley Stephanie , Smith Annette N. , Smith Ashley A. , Bergman Noelle , Sandey Maninder , Koehler Jey , Agarwal Payal , Smith Bruce F.
Published: April 2022

Despite significant advances in cancer diagnosis and treatment, osteosarcoma (OSA), an aggressive primary bone tumor, has eluded attempts at improving patient survival for many decades. The difficulty in managing OSA lies in its extreme genetic complexity, drug resistance, and heterogeneity, making it improbable that a single-target treatment would be beneficial for the majority of affected individuals. Precision medicine seeks to fill this gap by addressing the intra- and inter-tumoral heterogeneity to improve patient outcome and survival. The characterization of differentially expressed genes (DEGs) unique to the tumor provides insight into the phenotype and can be useful for informing appropriate therapies as well as the development of novel treatments. Traditional DEG analysis combines patient data to derive statistically inferred genes that are dysregulated in the group; however, the results from this approach are not necessarily consistent across individual patients, thus contradicting the basis of precision medicine. Spontaneously occurring OSA in the dog shares remarkably similar clinical, histological, and molecular characteristics to the human disease and therefore serves as an excellent model. In this study, we use transcriptomic sequencing of RNA isolated from primary OSA tumor and patient-matched normal bone from seven dogs prior to chemotherapy to identify DEGs in the group. We then evaluate the universality of these changes in transcript levels across patients to identify DEGs at the individual level. These results can be useful for reframing our perspective of transcriptomic analysis from a precision medicine perspective by identifying variations in DEGs among individuals.
Genetic Association of Beta-Lactams-Induced Hypersensitivity Reactions: A Protocol for Systematic Review and Meta-Analysis
Authors: Lumkul Lalita , Chuamanochan Mati , Nochaiwong Surapon , Sompornrattanaphan Mongkhon , Kulalert Prapasri , Lao-araya Mongkol , Wongyikul Pakpoom , Phinyo Phichayut
Published: April 2022

Beta-lactam (BL) antibiotics are among the drugs commonly related to hypersensitivity reactions. Several candidate gene studies and genome-wide association studies have reported associations of genetic variants and hypersensitivity reactions induced by BL antibiotics. However, the results were inconclusive. This protocol details a comprehensive systematic review of genetic factors associated with BL-induced hypersensitivity. A systematic search of literature related to genetic associations of BL-induced hypersensitivity will be performed through PubMed, Medline, Scopus, EMBASE, Web of Science, CINAHL, and the Cochrane central register of Controlled Trials (CENTRAL) from their inception dates with no language restrictions. Two reviewers will independently screen, extract, and appraise the risk of bias. Frequencies of genetic variants that comply with Hardy–Weinberg equilibrium will be extracted and pooled. Genetic models will be applied to variant effect calculation as per allele and genotype analysis. Based on statistical heterogeneity among studies, common effect estimation (odds ratio) and its corresponding 95% confidence interval will be analyzed. Sensitivity and subgroup analyses will be performed to determine the robustness of eligible studies. This systematic review and meta-analysis will provide comprehensive evidence of genetic effects regarding BL-induced hypersensitivity. The findings will enlighten the determination of disease-related genotypes that would potentially reveal allergy profiling in patients.
PanelDesign: Integrating Epidemiological Information into the Design of Diagnostic NGS Gene Panels
Authors: Schmidtke Jörg , Philipp Peter , Rommel Kathrin , Glaubitz Ralf , Epplen Jörg T. , Krawczak Michael
Published: April 2022

We report upon PanelDesign, a framework to support the design of diagnostic next generation DNA sequencing panels with epidemiological information. Two publicly available resources, namely Genomics England PanelApp and Orphadata, were combined into a single data set to allow genes in a given NGS panel to be ranked according to the frequency of the associated diseases, thereby highlighting potential core genes as defined by the Eurogenetest/ESHG guidelines for diagnostic next generation DNA sequencing. In addition, PanelDesign can be used to evaluate the contribution of different genes to a given disease following ACMG (American College of Medical Genetics) technical standards.
High Concentration or Combined Treatment of Antisense Oligonucleotides for Spinal Muscular Atrophy Perturbed SMN2 Splicing in Patient Fibroblasts
Authors: Wijaya Yogik Onky Silvana , Niba Emma Tabe Eko , Nishio Hisahide , Okamoto Kentaro , Awano Hiroyuki , Saito Toshio , Takeshima Yasuhiro , Shinohara Masakazu
Published: April 2022

Spinal muscular atrophy (SMA) is caused by survival motor neuron 1 SMN1 deletion. The survival motor neuron 2 (SMN2) encodes the same protein as SMN1 does, but it has a splicing defect of exon 7. Some antisense oligonucleotides (ASOs) have been proven to correct this defect. One of these, nusinersen, is effective in SMA-affected infants, but not as much so in advanced-stage patients. Furthermore, the current regimen may exhibit a ceiling effect. To overcome these problems, high-dose ASOs or combined ASOs have been explored. Here, using SMA fibroblasts, we examined the effects of high-concentration ASOs and of combining two ASOs. Three ASOs were examined: one targeting intronic splicing suppressor site N1 (ISS-N1) in intron 7, and two others targeting the 3′ splice site and 5′ region of exon 8. In our experiments on all ASO types, a low or intermediate concentration (50 or 100 nM) showed better splicing efficiency than a high concentration (200 nM). In addition, a high concentration of each ASO created a cryptic exon in exon 6. When a mixture of two different ASOs (100 nM each) was added to the cells, the cryptic exon was included in the mRNA. In conclusion, ASOs at a high concentration or used in combination may show less splicing correction and cryptic exon creation.
Robust Mutation Profiling of SARS-CoV-2 Variants from Multiple Raw Illumina Sequencing Data with Cloud Workflow
Authors: Lim Hendrick Gao-Min , Hsiao Shih-Hsin , Fann Yang C. , Lee Yuan-Chii Gladys
Published: April 2022

Several variants of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are emerging all over the world. Variant surveillance from genome sequencing has become crucial to determine if mutations in these variants are rendering the virus more infectious, potent, or resistant to existing vaccines and therapeutics. Meanwhile, analyzing many raw sequencing data repeatedly with currently available code-based bioinformatics tools is tremendously challenging to be implemented in this unprecedented pandemic time due to the fact of limited experts and computational resources. Therefore, in order to hasten variant surveillance efforts, we developed an installation-free cloud workflow for robust mutation profiling of SARS-CoV-2 variants from multiple Illumina sequencing data. Herein, 55 raw sequencing data representing four early SARS-CoV-2 variants of concern (Alpha, Beta, Gamma, and Delta) from an open-access database were used to test our workflow performance. As a result, our workflow could automatically identify mutated sites of the variants along with reliable annotation of the protein-coding genes at cost-effective and timely manner for all by harnessing parallel cloud computing in one execution under resource-limitation settings. In addition, our workflow can also generate a consensus genome sequence which can be shared with others in public data repositories to support global variant surveillance efforts.
Evaluating the Practices and Challenges of Youth Volleyball Development in Amhara Regional State, Ethiopia by Using the CIPP Model
Authors: Teshome Zemenu , Wolde Bezabeh , Abrham Teketel , Tadesse Tefera
Published: April 2022

Youth athletes’ talent identification and development has become a serious concern around the globe. However, empirical evidence regarding youth sports policies and practices is limited. Emphasizing the talent development needs of youth volleyball players, in this study, the authors evaluated the practices and challenges of a youth volleyball development program in Amhara Regional State, Ethiopia. This study addressed this concern by drawing upon Stufflebeam’s context, input, process, product (CIPP) model to explore a youth volleyball development program across the training sites located in Amhara Regional State, Ethiopia. With the help of this model, this study evaluated the prevailing contexts, allocated inputs, program implementation processes, and products. To this end, this study used multiple case studies involving ten youth project sites. The study participants included samples of participants (n = 179), consisting of youth volleyball players (n = 167), their coaches (n = 8), regional volleyball administrators, and regional educational office physical education coordinators (n = 4). The study participants identified some benefits from participating in the youth volleyball program, which included increased physical activity and health, enhanced positive interpersonal relationships, and knowledge of how to cope with challenges. However, they reported several challenges attributable to contextual constraints which included a lack of the necessary facilities and resources, lack of concern and convenient settings, poor implementation practices, and minimal outcomes. The findings suggest that the challenges of youth volleyball development in Ethiopia are complex and emanate from the context, input, process, and products. Accordingly, when addressing the issues of youth volleyball, it is necessary to develop systems, processes, methods, and tools that recognize all these concerns.
Budget Impact Analysis of Pharmacist-Led Medication Management in Cardiovascular and Type 2 Diabetic Patients
Authors: Mucalo Iva , Brajković Andrea , Strgačić Marija , Ramalho-de-Oliveira Djenane , Ribarić Elizabeta , Bobinac Ana
Published: April 2022

The paper aims to identify and measure the costs and savings associated with the delivery of Comprehensive Medication Management (CMM) services in Croatia in patients diagnosed with hypertension accompanied by at least one additional established cardiovascular disease (CVD) and/or type 2 diabetes mellitus (DMT2) who use five or more medicines daily. The budget impact analysis (BIA) employed in this study compares the total costs of CMM to the cost reductions expected from CMM. The cost reductions (or savings) are based on the reduced incidence of unwanted clinical events and healthcare service utilisation rates due to CMM. The BIA model is populated by data on medication therapy costs, labour, and training from the pilot CMM intervention introduced in Zagreb’s main Health Centre, while relevant international published sources were used to estimate the utilisation, incidence, and unwanted clinical events rates. Total direct costs, including pharmacists’ labour and training (EUR 2,667,098) and the increase in the cost of prescribed medication (EUR 5,182,864) amounted to EUR 7,849,962 for 3 years, rendering the cost per treated patient per year EUR 57. CMM is expected to reduce the utilisation rates of healthcare services and the incidence of unwanted clinical events, leading to a total 3-year reduction in healthcare costs of EUR 7,787,765. Given the total CMM costs of EUR 7,849,962, CMM’s 3-year budget impact equals EUR 92,869, rendering per treated patient an incremental cost of CMM EUR 0.67. Hence, CMM appears to be an affordable intervention for addressing medication mismanagement and irrational drug use.
Satisfaction with the Care Received and the Childbirth and Puerperium Experience in Christian and Muslim Pregnant Women
Authors: Fernández-Carrasco Francisco Javier , Silva-Muñoz Gustavo Adolfo , Vázquez-Lara Juana María , Gómez-Salgado Juan , García-Iglesias Juan Jesús , Rodríguez-Díaz Luciano
Published: April 2022

Over the last three decades, there has been an increase in the population as a result of the migratory flow due to the arrival of migrants to Spain, including young women of childbearing age and with reproductive capacity. This phenomenon has made childbirth assistance an extremely important priority in recent years. The aim of this study was to assess the satisfaction and experience during childbirth and the postpartum period in pregnant women according to their religion after assistance in a tertiary hospital. A descriptive cross-sectional study was conducted on a sample of 242 women using the validated Spanish version of the Mackey Childbirth Satisfaction Rating Scale (MCSRS) to measure satisfaction with the childbirth experience during the months of January to April 2021. Statistically significant differences were found in the domains of birth satisfaction (p < 0.01), satisfaction with the obstetrician (p < 0.01), and perception of pain during labour (p < 0.01). The Christian group of women scored higher in these three domains as compared to the Muslim group. The rate of breastfeeding at birth was 5.26 times higher among the Muslim group compared to the Christian group (p = 0.02). The experience of childbirth and the puerperium significantly influenced the levels of satisfaction of pregnant women with the process of childbirth in a different way according to the religious culture of the patient.
Checklist and New Occurrences of Odonata (Insecta) from Volta Grande do Xingu, Pará, Brazil
Authors: Carvalho-Soares Anderson André , Ferreira Kesley Gadelha , Sousa Kenned Silva , Nascimento Ana Caroline Leal , Mendoza-Penagos Cristian Camilo , Vieira Thiago Bernardi , Salcedo Ana Karina Moreyra , Oliveira-Junior José Max Barbosa , Calvão Lenize Batista , Dias-Silva Karina
Published: April 2022

The order Odonata (Insecta) is composed of aquatic insects popularly known as dragonflies and damselflies. Members of this order are closely linked to the conservation status of their habitats; however, the Wallacean shortfall in some regions still remains high. The Volta Grande do Xingu region is known to have high endemism of some groups, such as Actinopterygii (fish), which can be applied to other groups that do not yet have their fauna known at the site, such as the order Odonata. The Wallacean shortfall and constant anthropic changes (for example, the construction of the Belo Monte Hydroelectric) have been obstacles in the preservation of these and other groups. In that regard, the main aim of this paper is to provide a checklist of Odonata (Insecta) adult species from the streams of Volta Grande do Xingu, Pará, Brazil. The collections were carried out in 19 streams in the Volta Grande do Xingu region in September 2019, corresponding to the drought period. A total of 526 specimens were collected, where two suborders, six families, 26 genera and 43 species were identified. Three species of Odonata were registered for the first time in the state of Pará: Erythrodiplax famula (Erichson in Schomburgk, 1848); Acanthagrion chacoense Calvert, 1909 and Epipleoneura lamina Williamson, 1915. These data allow us to help increase the knowledge of Odonata fauna in the streams of Volta Grande do Xingu, a region that is under intense anthropic pressure. This helps to reduce the Wallacean shortfall, with another area sampled for the state of Pará.
Comment on Surendran et al. The Missed Opportunity of Patient-Centered Medical Homes to Thrive in an Asian Context. Int. J. Environ. Res. Public Health 2021, 18, 1817
Authors: Ngoh Sharon , Tang Wern Ee , Chng Edwin , Chong Phui-Nah
Published: April 2022

We have noted the views expressed by the authors of the article “The Missed Opportunity of Patient-Centered Medical Homes (PCMH) to Thrive in an Asian Context” by Surendran et al. [...]
APOB CRISPR-Cas9 Engineering in Hypobetalipoproteinemia: A Promising Tool for Functional Studies of Novel Variants
Authors: Vanhoye Xavier , Janin Alexandre , Caillaud Amandine , Rimbert Antoine , Venet Fabienne , Gossez Morgane , Dijk Wieneke , Marmontel Oriane , Nony Séverine , Chatelain Charlotte , Durand Christine , Lindenbaum Pierre , Rieusset Jennifer , Cariou Bertrand , Moulin Philippe , Di Filippo Mathilde
Published: April 2022

Hypobetalipoproteinemia is characterized by LDL-cholesterol and apolipoprotein B (apoB) plasma levels below the fifth percentile for age and sex. Familial hypobetalipoproteinemia (FHBL) is mostly caused by premature termination codons in the APOB gene, a condition associated with fatty liver and steatohepatitis. Nevertheless, many families with a FHBL phenotype carry APOB missense variants of uncertain significance (VUS). We here aimed to develop a proof-of-principle experiment to assess the pathogenicity of VUS using the genome editing of human liver cells. We identified a novel heterozygous APOB-VUS (p.Leu351Arg), in a FHBL family. We generated APOB knock-out (KO) and APOB-p.Leu351Arg knock-in Huh7 cells using CRISPR-Cas9 technology and studied the APOB expression, synthesis and secretion by digital droplet PCR and ELISA quantification. The APOB expression was decreased by 70% in the heterozygous APOB-KO cells and almost abolished in the homozygous-KO cells, with a consistent decrease in apoB production and secretion. The APOB-p.Leu351Arg homozygous cells presented with a 40% decreased APOB expression and undetectable apoB levels in cellular extracts and supernatant. Thus, the p.Leu351Arg affected the apoB secretion, which led us to classify this new variant as likely pathogenic and to set up a hepatic follow-up in this family. Therefore, the functional assessment of APOB-missense variants, using gene-editing technologies, will lead to improvements in the molecular diagnosis of FHBL and the personalized follow-up of these patients.
Stem Cell Homing in Intrathecal Applications and Inspirations for Improvement Paths
Authors: Maric Dusan M. , Velikic Gordana , Maric Dusica L. , Supic Gordana , Vojvodic Danilo , Petric Vedrana , Abazovic Dzihan
Published: April 2022

A transplanted stem cell homing is a directed migration from the application site to the targeted tissue. Intrathecal application of stem cells is their direct delivery to cerebrospinal fluid, which defines the homing path from the point of injection to the brain. In the case of neurodegenerative diseases, this application method has the advantage of no blood–brain barrier restriction. However, the homing efficiency still needs improvement and homing mechanisms elucidation. Analysis of current research results on homing mechanisms in the light of intrathecal administration revealed a discrepancy between in vivo and in vitro results and a gap between preclinical and clinical research. Combining the existing research with novel insights from cutting-edge biochips, nano, and other technologies and computational models may bridge this gap faster.
Potential Pro-Inflammatory Effect of Vitamin E Analogs through Mitigation of Tetrahydrocannabinol (THC) Binding to the Cannabinoid 2 Receptor
Authors: Manandhar Anjela , Haron Mona H. , Ross Samir A. , Klein Michael L. , Elokely Khaled M.
Published: April 2022

Vitamin E acetate, which is used as a diluent of tetrahydrocannabinol (THC), has been reported as the primary causative agent of e-cigarette, or vaping, product use-associated lung injury (EVALI). Here, we employ in vitro assays, docking, and molecular dynamics (MD) computer simulations to investigate the interaction of vitamin E with the membrane-bound cannabinoid 2 receptor (CB2R), and its role in modulating the binding affinity of THC to CB2R. From the MD simulations, we determined that vitamin E interacts with both CB2R and membrane phospholipids. Notably, the synchronized effect of these interactions likely facilitates vitamin E acting as a lipid modulator for the cannabinoid system. Furthermore, MD simulation and trajectory analysis show that when THC binds to CB2R in the presence of vitamin E, the binding cavity widens, facilitating the entry of water molecules into it, leading to a reduced interaction of THC with CB2R. Additionally, the interaction between THC and vitamin E in solution is stabilized by several H bonds, which can directly limit the interaction of free THCs with CB2R. Overall, both the MD simulations and the in vitro dissociation assay results indicate that THC binding to CB2R is reduced in the presence of vitamin E. Our study discusses the role of vitamin E in limiting the effect of THCs and its implications on the reported pathology of EVALI.
Storage Mite Precision Allergy Molecular Diagnosis in the Moderate-to-Severe T2-High Asthma Phenotype
Authors: González-Pérez Ruperto , Poza-Guedes Paloma , Pineda Fernando , Castillo Miriam , Sánchez-Machín Inmaculada
Published: April 2022

Storage mites (SM) may induce allergic respiratory symptoms in sensitized individuals, in both rural and urban settings. The relationship among specific IgE reactions to determined groups of SM allergens in the coincident asthma pheno-endotypes has not yet been investigated. We aimed to study a Precision Allergy Molecular Diagnosis (PAMD@) model to depict the SM molecular profile in individuals presenting with Type-2 inflammation, in two different (moderate and severe) asthma phenotypes. A customized PAMD@ panel, including SM allergens and their concurrent protein allergenic characterization was investigated. Mite group 2 allergens were most frequently recognized, including Lep d 2 (83.45%), followed by Gly d 2 (69.17%) and Tyr p 2 (47,37%), in 133/164 asthmatic subjects. Blo t 5 and Blo t 21 exhibited significant higher titres in both asthma groups. Although relevant mite group 2 allergens cross-reactivity is suggested, individualized sensitization patterns were relevantly identified. The present PAMD@ panel confirmed the dominance of mite group 2 allergens in moderate-to-severe T2 asthmatics. A broadly heterogeneous molecular repertoire of SM allergens was found in all subjects, regardless of their asthma severity. Blomia tropicalis deserves special attention in certain territories, as diagnostic and/or therapeutic approaches merely based on Pyroglyphidae mites may be insufficient.
COVID-19: Are We Facing Secondary Pellagra Which Cannot Simply Be Cured by Vitamin B3?
Authors: Novak Kujundžić Renata
Published: April 2022

Immune response to SARS-CoV-2 and ensuing inflammation pose a huge challenge to the host’s nicotinamide adenine dinucleotide (NAD+) metabolism. Humans depend on vitamin B3 for biosynthesis of NAD+, indispensable for many metabolic and NAD+-consuming signaling reactions. The balance between its utilization and resynthesis is vitally important. Many extra-pulmonary symptoms of COVID-19 strikingly resemble those of pellagra, vitamin B3 deficiency (e.g., diarrhoea, dermatitis, oral cavity and tongue manifestations, loss of smell and taste, mental confusion). In most developed countries, pellagra is successfully eradicated by vitamin B3 fortification programs. Thus, conceivably, it has not been suspected as a cause of COVID-19 symptoms. Here, the deregulation of the NAD+ metabolism in response to the SARS-CoV-2 infection is reviewed, with special emphasis on the differences in the NAD+ biosynthetic pathway’s efficiency in conditions predisposing for the development of serious COVID-19. SARS-CoV-2 infection-induced NAD+ depletion and the elevated levels of its metabolites contribute to the development of a systemic disease. Acute liberation of nicotinamide (NAM) in antiviral NAD+-consuming reactions potentiates “NAM drain”, cooperatively mediated by nicotinamide N-methyltransferase and aldehyde oxidase. “NAM drain” compromises the NAD+ salvage pathway’s fail-safe function. The robustness of the host’s NAD+ salvage pathway, prior to the SARS-CoV-2 infection, is an important determinant of COVID-19 severity and persistence of certain symptoms upon resolution of infection.
Obesity and Dyslipidemia Synergistically Exacerbate Psoriatic Skin Inflammation
Authors: Ikeda Kenta , Morizane Shin , Akagi Takahiko , Hiramatsu-Asano Sumie , Tachibana Kota , Yahagi Ayano , Iseki Masanori , Kaneto Hideaki , Wada Jun , Ishihara Katsuhiko , Morita Yoshitaka , Mukai Tomoyuki
Published: April 2022

Patients with psoriasis are frequently complicated with metabolic syndrome; however, it is not fully understood how obesity and dyslipidemia contribute to the pathogenesis of psoriasis. To investigate the mechanisms by which obesity and dyslipidemia exacerbate psoriasis using murine models and neonatal human epidermal keratinocytes (NHEKs), we used wild-type and Apoe-deficient dyslipidemic mice, and administered a high-fat diet for 10 weeks to induce obesity. Imiquimod was applied to the ear for 5 days to induce psoriatic dermatitis. To examine the innate immune responses of NHEKs, we cultured and stimulated NHEKs using IL-17A, TNF-α, palmitic acid, and leptin. We found that obesity and dyslipidemia synergistically aggravated psoriatic dermatitis associated with increased gene expression of pro-inflammatory cytokines and chemokines. Treatment of NHEKs with palmitic acid and leptin amplified pro-inflammatory responses in combination with TNF-α and IL-17A. Additionally, pretreatment with palmitic acid and leptin enhanced IL-17A-mediated c-Jun N-terminal kinase phosphorylation. These results revealed that obesity and dyslipidemia synergistically exacerbate psoriatic skin inflammation, and that metabolic-disorder-associated inflammatory factors, palmitic acid, and leptin augment the activation of epidermal keratinocytes. Our results emphasize that management of concomitant metabolic disorders is essential for preventing disease exacerbation in patients with psoriasis.
Expression Patterns of Sugar Transporter Genes in the Allocation of Assimilates and Abiotic Stress in Lily
Authors: Zeng Zhen , Lyu Tong , Jia Xin , Chen Yue , Lyu Yingmin
Published: April 2022

During the growth cycle of lilies, assimilates undergo a process of accumulation, consumption and reaccumulation in bulbs and are transported and allocated between aboveground and underground organs and tissues. The sink–source relationship changes with the allocation of assimilates, affecting the vegetative growth and morphological establishment of lilies. In this study, the carbohydrate contents in different tissues of five critical stages during lily development were measured to observe the assimilates allocation. The results showed bulbs acted as the main source to provide energy before the budding stage (S3); after the flowering stage (S4), bulbs began to accumulate assimilates as a sink organ again. During the period when the plant height was 30cm with leaf-spread (S2), leaves mainly accumulated assimilates from bulbs through the symplastic pathway, while when leaves were fully expanded, it transformed to export carbohydrates. At the S4 stage, flowers became a new active sink with assimilates influx. To further understand the allocation of assimilates, 16 genes related to sugar transport and metabolism (ST genes) were identified and categorized into different subfamilies based on the phylogenetic analysis, and their protein physicochemical properties were also predicted. Tissue-specific analysis showed that most of the genes were highly expressed in stems and petals, and it was mainly the MST (monosaccharide transporter) genes that were obviously expressed in petals during the S4 stage, suggesting that they may be associated with the accumulation of carbohydrates in flowers and thus affect flower development process. LoSWEET14 (the Sugar will eventually be exported transporters) was significantly correlated with starch in scales and with soluble sugar in leaves. Sugar transporters LoHXT6 and LoSUT1 were significantly correlated with soluble sugar and sucrose in leaves, suggesting that these genes may play key roles in the accumulation and transportation of assimilates in lilies. In addition, we analyzed the expression patterns of ST genes under different abiotic stresses, and the results showed that all genes were significantly upregulated. This study lays a solid foundation for further research on molecular mechanism of sink–source change and response to abiotic stresses in lilies.
Diagnostic Value of MAML2 Rearrangements in Mucoepidermoid Carcinoma
Authors: Thierauf Julia C. , Farahani Alex A. , Indave B. Iciar , Bard Adam Z. , White Valerie A. , Smith Cameron R. , Marble Hetal , Hyrcza Martin D. , Chan John K. C. , Bishop Justin , Shi Qiuying , Ely Kim , Agaimy Abbas , Martinez-Lage Maria , Nose Vania , Rivera Miguel , Nardi Valentina , Dias-Santagata Dora , Garg Salil , Sadow Peter , Le Long P. , Faquin William , Ritterhouse Lauren L. , Cree Ian A. , Iafrate A. John , Lennerz Jochen K.
Published: April 2022

Mucoepidermoid carcinoma (MEC) is often seen in salivary glands and can harbor MAML2 translocations (MAML2+). The translocation status has diagnostic utility as an objective confirmation of the MEC diagnosis, for example, when distinction from the more aggressive adenosquamous carcinoma (ASC) is not straightforward. To assess the diagnostic relevance of MAML2, we examined our 5-year experience in prospective testing of 8106 solid tumors using RNA-seq panel testing in combinations with a two-round Delphi-based scenario survey. The prevalence of MAML2+ across all tumors was 0.28% (n = 23/8106) and the majority of MAML2+ cases were found in head and neck tumors (78.3%), where the overall prevalence was 5.9% (n = 18/307). The sensitivity of MAML2 for MEC was 60% and most cases (80%) were submitted for diagnostic confirmation; in 24% of cases, the MAML2 results changed the working diagnosis. An independent survey of 15 experts showed relative importance indexes of 0.8 and 0.65 for “confirmatory MAML2 testing” in suspected MEC and ASC, respectively. Real-world evidence confirmed that the added value of MAML2 is a composite of an imperfect confirmation test for MEC and a highly specific exclusion tool for the diagnosis of ASC. Real-world evidence can help move a rare molecular-genetic biomarker from an emerging tool to the clinic.
AC-265347 Inhibits Neuroblastoma Tumor Growth by Induction of Differentiation without Causing Hypocalcemia
Authors: Gonçalves-Alves Eliana , Garcia Marta , Rodríguez-Hernández Carlos J. , Gómez-González Soledad , Ecker Rupert C. , Suñol Mariona , Muñoz-Aznar Oscar , Carcaboso Angel M. , Mora Jaume , Lavarino Cinzia , Mateo-Lozano Silvia
Published: April 2022

Neuroblastoma is the most common extracranial solid tumor of childhood, with heterogeneous clinical manifestations ranging from spontaneous regression to aggressive metastatic disease. The calcium-sensing receptor (CaSR) is a G protein-coupled receptor (GPCR) that senses plasmatic fluctuation in the extracellular concentration of calcium and plays a key role in maintaining calcium homeostasis. We have previously reported that this receptor exhibits tumor suppressor properties in neuroblastoma. The activation of CaSR with cinacalcet, a positive allosteric modulator of CaSR, reduces neuroblastoma tumor growth by promoting differentiation, endoplasmic reticulum (ER) stress and apoptosis. However, cinacalcet treatment results in unmanageable hypocalcemia in patients. Based on the bias signaling shown by calcimimetics, we aimed to identify a new drug that might exert tumor-growth inhibition similar to cinacalcet, without affecting plasma calcium levels. We identified a structurally different calcimimetic, AC-265347, as a promising therapeutic agent for neuroblastoma, since it reduced tumor growth by induction of differentiation, without affecting plasma calcium levels. Microarray analysis suggested biased allosteric modulation of the CaSR signaling by AC-265347 and cinacalcet towards distinct intracellular pathways. No upregulation of genes involved in calcium signaling and ER stress were observed in patient-derived xenografts (PDX) models exposed to AC-265347. Moreover, the most significant upregulated biological pathways promoted by AC-265347 were linked to RHO GTPases signaling. AC-265347 upregulated cancer testis antigens (CTAs), providing new opportunities for CTA-based immunotherapies. Taken together, this study highlights the importance of the biased allosteric modulation when targeting GPCRs in cancer. More importantly, the capacity of AC-265347 to promote differentiation of malignant neuroblastoma cells provides new opportunities, alone or in combination with other drugs, to treat high-risk neuroblastoma patients.
Atlantic Salmon Mucins Inhibit LuxS-Dependent A. Salmonicida AI-2 Quorum Sensing in an N-Acetylneuraminic Acid-Dependent Manner
Authors: Padra János Tamás , Loibman Stefany Ojaimi , Thorell Kaisa , Sundh Henrik , Sundell Kristina , Lindén Sara K.
Published: April 2022

One of the most important bacterial diseases in salmonid aquaculture is furunculosis, caused by Aeromonas salmonicida. Bacterial communication through secreted autoinducer signals, quorum sensing, takes part in the regulation of gene expression in bacteria, influencing growth and virulence. The skin and mucosal surfaces, covered by a mucus layer, are the first point of contact between fish and bacteria. Mucins are highly glycosylated and are the main components of mucus. Here, we validate the Vibrio harveyi BB170 bioreporter assay for quantifying A. salmonicida quorum sensing and study the effects of Atlantic salmon mucins as well as mono- and disaccharides on the AI-2 levels of A. salmonicida. Atlantic salmon mucins from skin, pyloric ceca, proximal and distal intestine reduced A. salmonicida AI-2 levels. Among the saccharides abundant on mucins, fucose, N-acetylneuraminic acid and GlcNAcβ1-3Gal inhibited AI-2 A. salmonicida secretion. Removal of N-acetylneuraminic acid, which is the most abundant terminal residue on mucin glycans on Atlantic salmon mucins, attenuated the inhibitory effects on AI-2 levels of A. salmonicida. Deletion of A. salmonicida luxS abolished AI-2 production. In conclusion, Atlantic salmon mucins regulate A. salmonicida quorum sensing in a luxS and N-acetylneuraminic acid-dependent manner.
Inhibitory Effect of CUSTOS, a Formulated Allium-Based Extract, on the Growth of Some Selected Plant Pathogens
Authors: Oladejo Oluwashina , Imani Jafargholi
Published: April 2022

Plants are in intimate association with a great diversity of pathogenic and mutualistic microbes that use host plants for proliferation. Plants, in turn, have evolved mechanisms that are contingent upon their innate immune system to resist perceived biotic stresses. The objective of this work is to determine the antimicrobial properties of an allium-based antimicrobial formulation named CUSTOS on the growth of plant pathogenic microorganisms such as fungi, oomycetes, and bacteria. Two anthracnose-related species of the fungal genus Colletotrichum, Colletotrichum gloeosporioides, the oomycete Phytophthora cactorum, and the bacterium Xanthomonas fragariae associated with strawberry plants were tested in vitro. Furthermore, two fungi Alternaria dauci and Botrytis cinerea, associated with carrot plants, were tested in planta. CUSTOS inhibited the growth of all plant pathogens tested. We found that both curative and preventive planta treatments with CUSTOS inhibited the growth of Alternaria dauci and Botrytis cinerea in carrots. Furthermore, the differential expression levels of the PR 10 genes were correlated with the magnitude of infection. We also found that the field application of CUSTOS on strawberry plants results in a reduction of fungal pathogens on strawberry fruits stored under refrigeration. In summary, CUSTOS may induce pathogen resistance in fruit and vegetable plants and can be used as both a curative and a preventive against rotting and disease.
Electrocatalyst Derived from NiCu–MOF Arrays on Graphene Oxide Modified Carbon Cloth for Water Splitting
Authors: Jia Lisha , Wagner Pawel , Chen Jun
Published: April 2022

Electrocatalysts are capable of transforming water into hydrogen, oxygen, and therefore into energy, in an environmentally friendly and sustainable manner. However, the limitations in the research of high performance catalysts act as an obstructer in the development of using water as green energy. Here, we report on a delicate method to prepare novel bimetallic metal organic framework derived electrocatalysts (C–NiCu–BDC–GO–CC) using graphene oxide (GO) modified carbon cloth as a 3D flexible and conductive substrate. The resultant electrocatalyst, C–NiCu–BDC–GO–CC, exhibited very low electron transfer resistance, which benefited from its extremely thin 3D sponge-like morphology. Furthermore, it showed excellent oxygen evolution reaction (OER) activity, achieving 10 mA/cm2 at a low overpotential of 390 mV in 1 M KOH electrolyte with a remarkable durability of 10 h.
Potential of Antimicrobial Peptide-Overexpressed Tenebrio molitor Larvae Extract as a Natural Preservative for Korean Traditional Sauces
Authors: Hwang Dooseon , Lee Seung , Goo Tae-Won , Yun Eun-Young
Published: April 2022

Here, we aimed to produce a natural food preservative using a crude extract from edible, immunized Tenebrio molitor larvae (iTME), injected with edible bacteria using an edible solvent. Results showed that iTME had concentration-dependent inhibitory activity against food-poisoning bacteria Escherichia coli, Bacillus cereus, and Staphylococcus aureus, as well as against harmful fungi Aspergillus flavus, Aspergillus parasiticus, and Pichia anomala. Moreover, iTME showed antimicrobial activity against beneficial microorganisms Bacillus subtilis and Aspergillus oryzae, but not Lactobacillus acidophilus. Furthermore, the minimum inhibitory concentration of iTME against E. coli, B. cereus, and S. aureus was 1 mg/mL, and iTME did not lose its inhibitory activity when treated at varying temperature, pH, and salinity. In addition, the antibacterial activity was lost after reacting the iTME with trypsin and chymotrypsin. The addition of iTME to Ganjang inoculated with harmful bacteria inhibited bacterial growth. Therefore, we propose that iTME can be used as a safe natural preservative to prolong food shelf life by inhibiting the growth of food-poisoning bacteria in a variety of foods, including traditional sauces.
Genetic Variability of Polypedilum (Diptera: Chironomidae) from Southwest Ecuador
Authors: Ballesteros Isabel , Bravo-Castro Mishell , Villamarín-Cortez Santiago , Jijón Gabriela , Prat Narcís , Ríos-Touma Blanca , Villamarín Christian
Published: April 2022

Chironomids show a wide distribution and can occupy several habitats due to their high adaptive capacity in different freshwater environments. The genus Polypedilum is found along a wide elevational and environmental gradient in the neotropics, and its genetic variability could help to elucidate factors determining its distribution and tolerance to the environmental changes of different species or populations. This study examines the genetic variability of Polypedilum in an important biogeographic area that acts as a geographical barrier of biodiversity at the border of the Choco and Tumbes biomes. We identified five Polypedilum morphotypes using classic taxonomic methods. We examined 68 Polypedilum individuals from eight sampling sites in El Oro Province, Ecuador, analyzing the putative molecular species using the cytochrome c oxidase subunit 1 (CO1) mitochondrial gene fragment. Then, we calculated molecular diversity indices, Haplotype diversity (Hd), and θs and θπ estimators. Seven Polypedilum OTUs were determined from which a high molecular diversity was registered. A CCA was conducted to understand the population composition in relation to environmental characteristics. Results indicated that dissolved oxygen and temperature are the main environmental factors affecting Polypedilum distribution across elevational gradients and between basins.
CRISPR/Cas9-Mediated Mutagenesis of Abdominal-A and Ultrabithorax in the Asian Corn Borer, Ostrinia furnacalis
Authors: Bi Honglun , Merchant Austin , Gu Junwen , Li Xiaowei , Zhou Xuguo , Zhang Qi
Published: April 2022

(1) Background: Abdominal-A (Abd-A) and Ultrabithorax (Ubx) are homeotic genes that determine the identity and morphology of the thorax and abdomen in insects. The Asian corn borer, Ostrinia furnacalis (Guenée) (Lepidoptera: Pyralidae), is a devastating maize pest throughout Asia, the Western Pacific, and Australia. Building on previous knowledge, we hypothesized that the knockout of Abd-A and Ubx would disrupt the abdominal body planning in O. furnacalis. (2) Methods: CRISPR/Cas9-targeted mutagenesis was employed to decipher the functions of these homeotic genes. (3) Results: Knockout insects demonstrated classical homeotic transformations. Specifically, the mutagenesis of OfAbd-A resulted in: (1) Fused segments and segmental twist during the larval stage; (2) Embryonic lethality; and (3) The pleiotropic upregulation of other homeotic genes, including Lab, Pd, Dfd, Antp, and Abd-B. The mutagenesis of OfUbx led to: (1) Severe defects in the wing pads, which limited the ability of the adults to fly and mate; (2) Female sterility; and (3) The pleiotropic upregulation of other homeotic genes, including Dfd, Abd-B, and Wnt1. (4) Conclusions: These combined results not only support our hypothesis, but they also strengthen the potential of using homeotic genes as molecular targets for the genetic control of this global insect pest.