Miracle-dz/UniFAR-FTUs huggingface dataset:
Determining genetic variants in children and adolescents suffering from Tetralogy of Fallot with a positive family history: methodology

Background and aim: Congenital heart disease (CHD) affects close to 1% of all live births and is considered as the main reason for morbidity and mortality in early childhood. In this study, we aimed to investigate molecular genetic factors associated with Tetralogy of Fallot (TOF), using high throughput technologies in the consanguineous families with at least two affected individuals. Method: This family study started from March 2017 to May 2019, in the pediatric cardiovascular research center, Cardiovascular Research Institute, Isfahan, Iran. Families with consanguineous marriage who had at least two patients in pedigree were invited to attend. Genomic DNA was extracted from peripheral blood lymphocytes of the patient and samples were investigated for variations such as deletion or duplication in the genome, using single nucleotide polymorphism array (SNP array). In the next step, if the SNP array was negative, the next generation sequencing (NGS) was performed in the probands. The raw data was analyzed and filtered to identify the genetic cause of the disease. Results: In this study, total five families were evaluated. All affected and unaffected individuals of each family included in the pedigree. Fourteen subjects, 9 males and 5 females, 8.92±6.21 years old were included. The prevalence of consanguineous marriage was 92.2% among parents, 71.4% among maternal grandparents and 28.6% among paternal grandparents. Almost, 64.3% of our participants had a sibling with a similar disease. The prevalence of Atrial Septal Defect (ASD), Ventricular Septal Defect (VSD), and arrhythmia and TOF was 7.1%. Conclusion: We found some families with two or more CHD cases and with high rate of consanguineous marriage, having a genetic predisposition. In the next step, high throughput techniques such as NGS and SNP-array was performed in order to find any genetic variation. Functional study will be done, to confirm and determine the role of the identified variants in the function of genes involved in disease phenotype. (www.actabiomedica.it)
Comparison of Genetically Engineered Immunodeficient Animal Models for Nonclinical Testing of Stem Cell Therapies

For the recovery or replacement of dysfunctional cells and tissue—the goal of stem cell research—successful engraftment of transplanted cells and tissues are essential events. The event is largely dependent on the immune rejection of the recipient; therefore, the immunogenic evaluation of candidate cells or tissues in immunodeficient animals is important. Understanding the immunodeficient system can provide insights into the generation and use of immunodeficient animal models, presenting a unique system to explore the capabilities of the innate immune system. In this review, we summarize various immunodeficient animal model systems with different target genes as valuable tools for biomedical research. There have been numerous immunodeficient models developed by different gene defects, resulting in many different features in phenotype. More important, mice, rats, and other large animals exhibit very different immunological and physiological features in tissue and organs, including genetic background and a representation of human disease conditions. Therefore, the findings from this review may guide researchers to select the most appropriate immunodeficient strain, target gene, and animal species based on the research type, mutant gene effects, and similarity to human immunological features for stem cell research.
Design of a diagnostic system based on molecular markers derived from the ascomycetes pan-genome analysis: The case of Fusarium dieback disease

A key factor to take actions against phytosanitary problems is the accurate and rapid detection of the causal agent. Here, we develop a molecular diagnostics system based on comparative genomics to easily identify fusariosis and specific pathogenic species as the Fusarium kuroshium, the symbiont of the ambrosia beetle Euwallaceae kuroshio Gomez and Hulcr which is responsible for Fusarium dieback disease in San Diego CA, USA. We performed a pan-genome analysis using sixty-three ascomycetes fungi species including phytopathogens and fungi associated with the ambrosia beetles. Pan-genome analysis revealed that 2,631 orthologue genes are only shared by Fusarium spp. , and on average 3,941 (SD ± 1,418.6) are species-specific genes. These genes were used for PCR primer design and tested on DNA isolated from i) different strains of ascomycete species, ii) artificially infected avocado stems and iii) plant tissue of field-collected samples presumably infected. Our results let us propose a useful set of primers to either identify any species from Fusarium genus or, in a specific manner, species such as F. kuroshium, F. oxysporum, and F. graminearum. The results suggest that the molecular strategy employed in this study can be expanded to design primers against different types of pathogens responsible for provoking critical plant diseases.
Animal Models in the Evaluation of the Effectiveness of Phage Therapy for Infections Caused by Gram-Negative Bacteria from the ESKAPE Group and the Reliability of Its Use in Humans

The authors emphasize how extremely important it is to highlight the role played by animal models in an attempt to determine possible phage interactions with the organism into which it was introduced as well as to determine the safety and effectiveness of phage therapy in vivo taking into account the individual conditions of a given organism and its physiology. Animal models in which phages are used make it possible, among other things, to evaluate the effective therapeutic dose and to choose the possible route of phage administration depending on the type of infection developed. These results cannot be applied in detail to the human body, but the knowledge gained from animal experiments is invaluable and very helpful. We would like to highlight how useful animal models may be for the possible effectiveness evaluation of phage therapy in the case of infections caused by gram-negative bacteria from the ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species) group of pathogens. In this review, we focus specifically on the data from the last few years.
High-Sensitivity High-Throughput Detection of Nucleic Acid Targets on Metasurface Fluorescence Biosensors

Worldwide infection disease due to SARS-CoV-2 is tremendously affecting our daily lives. High-throughput detection methods for nucleic acids are emergently desired. Here, we show high-sensitivity and high-throughput metasurface fluorescence biosensors that are applicable for nucleic acid targets. The all-dielectric metasurface biosensors comprise silicon-on-insulator nanorod array and have prominent electromagnetic resonances enhancing fluorescence emission. For proof-of-concept experiment on the metasurface biosensors, we have conducted fluorescence detection of single-strand oligoDNAs, which model the partial sequences of SARS-CoV-2 RNA indicated by national infection institutes, and succeeded in the high-throughput detection at low concentrations on the order of 100 amol/mL without any amplification technique. As a direct detection method, the metasurface fluorescence biosensors exhibit high performance.
Tackling Food Insecurity in Cabo Verde Islands: The Nutritional, Agricultural and Environmental Values of the Legume Species

Legume species are important food sources to reduce hunger and deal with malnutrition; they also play a crucial role in sustainable agriculture in the tropical dry islands of Cabo Verde. To improve the knowledge of the heritage of plant genetic resources in this Middle Income Country, this study had three main goals: (i) to provide a checklist of food legumes; (ii) to investigate which species are traded in local markets and, based on field surveys, to compare species for their chemical, phenolic, antioxidant, and nutritional composition; and (iii) to discuss the agronomic value and contribution to food security in this archipelago. Our results revealed that 15 species are used as food and 5 of them are locally traded (Cajanus cajan, Lablab purpureus, Phaseolus lunatus, Phaseolus vulgaris, and Vigna unguiculata). The role of these species as sources of important minerals, antioxidants, and nutritional components for food security is highlighted, and the native ones (Lablab purpureus and Vigna unguiculata) stand-out as particularly well-adapted to the climate of these islands, which are already experiencing the adverse effects of climate change. We conclude that the sustainable use of these genetic resources can contribute to the reduction of hunger and poverty, thus meeting some challenges of the Sustainable Development Goals.
Association of Inflammatory and Insulinemic Potential of Diet and Lifestyle with Risk of Hepatocellular Carcinoma

Background: We prospectively examined the extent to which greater inflammatory and insulinemic potential of diet and lifestyle are associated with the risk of developing hepatocellular carcinoma (HCC) in two nationwide cohorts. Methods: Five kinds of pattern scores, including the empirical dietary inflammatory pattern (EDIP), empirical dietary index for hyperinsulinemia (EDIH) and insulin resistance (EDIR), empirical lifestyle pattern score for hyperinsulinemia (ELIH) and insulin resistance (ELIR) were calculated. Multivariable hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression. Results: After an average follow-up of 25.6 years among 119,316 participants, 142 incident HCC cases were documented. Higher adherence to EDIP (HR by comparing extreme tertiles: 2.03; 95% CI, 1.31–3.16; Ptrend = 0.001), EDIH (HR, 1.61; 95% CI, 1.06–2.43; Ptrend = 0.02), and EDIR (HR, 1.62; 95% CI: 1.08–2.42; Ptrend = 0.02) was associated with increased risk of HCC. Likewise, participants with higher scores of ELIH (HR, 1.89; 95% CI, 1.25–2.87; Ptrend = 0.001) and ELIR (HR, 2.05; 95% CI, 1.34–3.14, Ptrend = 0.0004) had higher risk of developing HCC. Additional adjustment for diabetes mellitus and/or body mass index attenuated the magnitude of the associations, indicating that diabetes and/or adiposity may partly mediate the association of these patterns with HCC risk. Conclusions: Our findings suggest that inflammation and insulin resistance/hyperinsulinemia are potential mechanisms linking dietary or lifestyle factors and HCC development. Impact: Inflammation and insulin resistance/hyperinsulinemia may partly mediate the association of diet and other lifestyles with HCC development, and interventions to reduce the adverse effect of pro-inflammatory and hyperinsulinemic diet and lifestyle may reduce HCC risk.
Assessment of the Nutraceutical Effects of Oleuropein and the Cytotoxic Effects of Adriamycin, When Administered Alone and in Combination, in MG-63 Human Osteosarcoma Cells

Oleuropein (OLEU) is the most distinguished phenolic compound found in olive fruit and the leaves of Olea europaea L. , with several pharmacological properties, including anti-cancer actions. Adriamycin (ADR) is an anthracycline widely used as a chemotherapeutic agent, although it presents significant side effects. The aim of the present study was to investigate the effect of oleuropein alone (20 μg/mL) and in co-treatment with ADR (50 nM), in MG-63 human osteosarcoma cells. Therefore, cellular and molecular techniques, such as MTT assay, flow cytometry, real-time Polymerase Chain Reaction (PCR), western blot and Elisa method, as well as Nuclear Magnetic Resonance (NMR) spectroscopy, were applied to unveil changes in the signal transduction pathways involved in osteosarcoma cells survival. The observed alterations in gene, protein and metabolite levels denote that OLEU not only inhibits MG-63 cells proliferation and potentiates ADR’s cytotoxicity, but also exerts its action, at least in part, through the induction of autophagy.
Relationships between resilience and quality of life in parents of children with cancer

A child suffering from cancer can be considerably stressful for parents, exerting a negative impact on their psychological well-being and quality of life. This study explored the relationships between resilience and quality of life in parents of children with cancer. We recruited 146 parents of children with cancer in two tertiary hospitals in mainland China. The results revealed that greater parental resilience was associated with better quality of life. It is essential to develop interventions that can enhance resilience for parents of children with cancer, thereby improving their quality of life. ClinicalTrials.gov ID: NCT03631485
A Comparative Investigation on Phenolic Composition, Characterization and Antioxidant Potentials of Five Different Australian Grown Pear Varieties

Pear (Pyrus communis L.) is widely spread throughout the temperate regions of the world, such as China, America and Australia. This fruit is popular among consumers due to its excellent taste and perceived health benefits. Various bioactive compounds, which contribute to these health benefits, have been detected in the pear fruits, including a range of phenolic compounds. Five Australian grown pear varieties, which include Packham’s Triumph, Josephine de Malines, Beurre Bosc, Winter Nelis and Rico were selected for this study to examine the phenolic compounds in pears. Beurre Bosc exhibited the highest total polyphenol content (TPC) (3.14 ± 0.02 mg GAE/g), total tannin content (TTC) (1.43 ± 0.04 mg CE/g) and 2,2′-diphenyl-1-picrylhydrazyl (DPPH) (5.72 ± 0.11 mg AAE/g), while the Josephine de Malines variety was high in total flavonoid content (TFC) (1.53 ± 0.09 mg QE/g), ferric reducing antioxidant power (FRAP) (4.37 ± 0.04 mg AAE/g), 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) (4.44 ± 0.01 mg AAE/g) and total antioxidant capacity (TAC) (5.29 ± 0.09 mg AAE/g). The liquid chromatography coupled with electrospray-ionization quadrupole time-of-flight mass spectrometry (LC-ESI-QTOF-MS/MS) data indicate that a total of 73 phenolic compounds were detected in Beurre Bosc (37 compounds), Josephine de Malines (34), Rico (22), Packham’s Triumph (15) and Winter Nelis (9), respectively. From HPLC-PDA quantification, the Beurre Bosc pear variety showed significantly higher in phenolic acids (chlorogenic acid; 17.58 ± 0.88 mg/g) and while flavonoids were significantly higher in Josephine de Malines (catechin; 17.45 ± 1.39 mg/g), as compared to other pear varieties. The analyses suggest that the Australian grown pears might contain an ideal source of phenolic compounds which benefit human health. The information provided by the present work can serve as practical supporting data for the use of pears in the nutraceutical, pharmaceutical and food industries.
Validation of common reference genes stability in exosomal mRNA‐isolated from liver and breast cancer cell lines

Accurate relative gene expression analysis by reverse transcription‐quantitative polymerase chain reaction relies on the usage of suitable reference genes for data normalization. The RNA content of small extracellular vesicles including exosomes is growingly considered as cancer biomarkers. So, reliable relative quantification of exosomal messenger RNA (mRNA) is essential for cancer diagnosis and prognosis applications. However, suitable reference genes for accurate normalization of a target gene in exosomes derived from cancer cells are not depicted yet. Here, we analyzed the expression and stability of eight well‐known reference genes namely GAPDH, B2M, HPRT1, ACTB, YWHAZ, UBC, RNA18S, and TBP in exosomes‐isolated from the liver (Huh7, HepG2, PLC/PRF/5) and breast (SK‐BR‐3) cancer cell lines using five different algorithms including geNorm, BestKeeper, Delta Ct, NormFinder, and RefFinder. Our results showed that ACTB, TBP, and HPRT1 were not expressed in exosomes‐isolated from studied liver and breast cancer cell lines. The geNorm and BestKeeper algorithms indicated GAPDH and UBC as the most stable candidates. Moreover, Delta Ct and NormFinder algorithms showed YWHAZ as the most stable reference genes. Comprehensive ranking calculated by the RefFinder algorithm also pointed out GAPDH, YWHAZ, and UBC as the first three stable reference genes. Taken together, this study validated the common reference genes stability in exosomal mRNA derived from liver and breast cancer cell lines for the first time. We believe that this study would be the first step in finding more stable reference genes in exosomes that triggers more accurate detection of exosomal biomarkers.
Müller glia–myeloid cell crosstalk accelerates optic nerve regeneration in the adult zebrafish

Neurodegenerative disorders, characterized by progressive neuronal loss, eventually lead to functional impairment in the adult mammalian central nervous system (CNS). Importantly, these deteriorations are irreversible, due to the very limited regenerative potential of these CNS neurons. Stimulating and redirecting neuroinflammation was recently put forward as an important approach to induce axonal regeneration, but it remains elusive how inflammatory processes and CNS repair are intertwined. To gain more insight into these interactions, we investigated how immunomodulation affects the regenerative outcome after optic nerve crush (ONC) in the spontaneously regenerating zebrafish. First, inducing intraocular inflammation using zymosan resulted in an acute inflammatory response, characterized by an increased infiltration and proliferation of innate blood‐borne immune cells, reactivation of Müller glia, and altered retinal cytokine expression. Strikingly, inflammatory stimulation also accelerated axonal regrowth after optic nerve injury. Second, we demonstrated that acute depletion of both microglia and macrophages in the retina, using pharmacological treatments with both the CSF1R inhibitor PLX3397 and clodronate liposomes, compromised optic nerve regeneration. Moreover, we observed that csf1ra/b double mutant fish, lacking microglia in both retina and brain, displayed accelerated RGC axonal regrowth after ONC, which was accompanied with unusual Müller glia proliferative gliosis. Altogether, our results highlight the importance of altered glial cell interactions in the axonal regeneration process after ONC in adult zebrafish. Unraveling the relative contribution of the different cell types, as well as the signaling pathways involved, may pinpoint new targets to stimulate repair in the vertebrate CNS.
Effect of Enteral Lipid Supplement on Severe Retinopathy of Prematurity

Key Points Question Does enteral fatty acid supplementation with arachidonic acid (AA) and docosahexaenoic acid (DHA) from birth to 40 weeks’ postmenstrual age reduce severe retinopathy of prematurity (ROP) in extremely preterm infants? Findings This randomized clinical trial found that enteral AA and DHA supplementation lowered the risk of severe ROP by 50%. In addition, the group that received enteral AA and DHA supplementation showed higher serum levels of both AA and DHA compared with controls. Meaning Supplementing the diet of the most immature infants born at less than 27 weeks’ gestational age with an enteral lipid solution with AA:DHA had no significant adverse effects and seems to be a promising intervention to prevent sight-threatening ROP and thereby reduce visual impartment and blindness.
Control Design With Optimization for Fuzzy Steering-by-Wire System Based on Nash Game Theory

In this article, we apply a high-order control to a dynamical system with uncertainty. There are two characteristics. First, the uncertain part, which is time-varying but bounded, is described in a fuzzy aspect. Specifically, the uncertainty lies within a fuzzy set and the bound is regarded as a fuzzy number. Second, the systems are uniformly bounded and uniformly ultimately bounded with a deterministic controller based on the Lyapunov theory. To obtain better system performance and lower control input, we apply the noncooperative game theory to optimize the parameters by establishing a Nash game. Then, the D-operation is proposed for the uncertainty related to fuzzy numbers. Finally, we perform the numerical simulations of the steering-by-wire system for verification.
Correction

APPLIED BIOLOGICAL SCIENCES Correction for “Lipid-like materials for low-dose, in vivo gene silencing,” by Kevin T. Love, Kerry P. Mahon, Christopher G. Levins, Kathryn A. Whitehead, William Querbes, J. Robert Dorkin, June Qin, William Cantley, Liu Liang Qin, Timothy Racie, Maria Frank-Kamenetsky, Ka Ning Yip, Rene Alvarez, Dinah W. Y. Sah, Antonin de Fougerolles, Kevin Fitzgerald, Victor Koteliansky, Akin Akinc, Robert Langer, and Daniel G. Anderson, which appeared in issue 5, February 2, 2010, of Proc Natl Acad Sci USA (107:1864–1869; first published January 11, 2010; 10.1073/pnas.0910603106). The authors note that due to a printer’s error, the caption for Fig. 2 did not appear in full. The caption “(B) Luciferase” should instead appear as “(B) Luciferase silencing at low doses of siRNA (s.d., n = 4). ” The figure and its corrected legend appear below.
Prognostic Value of Plasma hPG80 (Circulating Progastrin) in Metastatic Renal Cell Carcinoma

Simple Summary Metastatic renal cell carcinoma (mRCC) accounts for one-third of all newly diagnosed renal cell cancers. A better understanding of the biology and molecular basis of disease progression has resulted in several drug targets being identified and led to approval of several new drugs for treating mRCC in the past decade. A growing need has emerged for identifying novel molecular tumor biology based and stage-specific prognostic and predictive biomarkers in mRCC reflective of biology beyond the currently available prognostic models which are solely based on clinical characteristics. We investigated hPG80 (circulating progastrin), which is associated with kidney cancer biology and found that hPG80 levels is both an independent prognostic marker in mRCC and also improves current clinical prognostic models. This will help stratify mRCC patients more accurately in future and improve the management of mRCC patients. Abstract Precise management of kidney cancer requires the identification of prognostic factors. hPG80 (circulating progastrin) is a tumor promoting peptide present in the blood of patients with various cancers, including renal cell carcinoma (RCC). In this study, we evaluated the prognostic value of plasma hPG80 in 143 prospectively collected patients with metastatic RCC (mRCC). The prognostic impact of hPG80 levels on overall survival (OS) in mRCC patients after controlling for hPG80 levels in non-cancer age matched controls was determined and compared to the International Metastatic Database Consortium (IMDC) risk model (good, intermediate, poor). ROC curves were used to evaluate the diagnostic accuracy of hPG80 using the area under the curve (AUC). Our results showed that plasma hPG80 was detected in 94% of mRCC patients. hPG80 levels displayed high predictive accuracy with an AUC of 0.93 and 0.84 when compared to 18–25 year old controls and 50–80 year old controls, respectively. mRCC patients with high hPG80 levels (>4.5 pM) had significantly lower OS compared to patients with low hPG80 levels (<4.5 pM) (12 versus 31.2 months, respectively; p = 0.0031). Adding hPG80 levels (score of 1 for patients having hPG80 levels > 4.5 pM) to the six variables of the IMDC risk model showed a greater and significant difference in OS between the newly defined good-, intermediate- and poor-risk groups (p = 0.0003 compared to p = 0.0076). Finally, when patients with IMDC intermediate-risk group were further divided into two groups based on hPG80 levels within these subgroups, increased OS were observed in patients with low hPG80 levels (<4.5 pM). In conclusion, our data suggest that hPG80 could be used for prognosticating survival in mRCC alone or integrated to the IMDC score (by adding a variable to the IMDC score or by substratifying the IMDC risk groups), be a prognostic biomarker in mRCC patients.