Miracle-dz/UniFAR-FTUs huggingface dataset:
Metabolomic Variability of Different Soybean Genotypes: β-Carotene-Enhanced (Glycine max), Wild (Glycine soja), and Hybrid (Glycine max × Glycine soja) Soybeans

We obtained a new hybrid soybean (Hybrid) by hybridizing β-carotene-enhanced soybean (BCE; Glycine max L.) containing the phytoene synthase-2A-carotene desaturase gene and wild-type soybean (Wild; Glycine soja). To investigate metabolic changes between variants, we performed metabolic profiling of leaves (three growth stages) and seeds. Multivariate analyses revealed significant metabolic differences between genotypes in seeds and leaves, with seeds showing accumulation of phytosterols, tocopherols, and carotenoids (BCE only), indicating co-induction of the methylerythritol 4-phosphate and mevalonic acid pathways. Additionally, Hybrid produced intermediate levels of carotenoids and high levels of amino acids. Principal component analysis revealed metabolic discrimination between growth stages of soybean leaves and identified differences in leaf groups according to different genotypes at 8, 12, and 16 weeks, with Wild showing higher levels of environmental stress-related compounds relative to BCE and Hybrid leaves. The metabolic profiling approach could be a useful tool to identify metabolic links in various soybean cultivars.
Prevalence and Impact of the Relative Age Effect on Competition Performance in Swimming: A Systematic Review

This systematic review aimed to examine the prevalence of the relative age effect (RAE) in swimming and its impact on competition performance according to different types of interacting constraints. A systematic literature search, following the PRISMA guidelines for preparing systematic reviews, was performed through four electronic databases, and nine studies met the inclusion criteria. The quality of the selected studies was evaluated using STROBE, and an average score of 16.2 points was obtained. In these studies, the prevalence of the RAE in swimming was observed in more than half (58.65%) of the participants analysed, and the effect of the RAE was more accentuated in young categories (decreased as age increased and was inverted in older ones) and in male swimmers (double that in female swimmers). The impact of the RAE on competitive performance appeared to be related to the strength demands of the event, as the performance in simultaneous strokes, in shorter events, and of swimmers in the postadolescence period seems to be more affected by the RAE. These results indicate that the RAE in competitive swimming relies on individual and environmental (the swimmer’s age group and gender) but also task (the competitive events) determinants or limitations. This should serve as a guide for a more effective design of selection and development procedures for young athletes.
Coping Strategies and Stress Related Disorders in Patients with COVID-19

Patients with severe COVID-19 experience high-stress levels and thus are at risk for developing acute stress disorder (ASD) and/or post-traumatic stress disorder (PTSD). The present study aims to search for correlations between psychiatric response to stress and coping strategies among individuals with acute vs. remitted COVID-19. Ninety subjects with COVID-19 were included in the study, divided into two samples by disease category. Our focus was analysing the perceived stress intensity according to NSESSS and PCL-C-17 scales, and coping strategies with COPE-60. High NSESSS scores were found in 40% of acute patients, and 15.6% of remitted patients had high PCL-C-17 scores fulfilling the criteria for PTSD. We found a negative correlation between stress level and disease category. Acute patients used significantly more engagement and emotion-focused coping methods, but less disengagement types of coping than patients in the remitted phase. Remitted patients under high stress levels are prone to use disengagement and emotion-focused coping strategies. In conclusion, remitted COVID-19 patients experience lower levels of stress and use less emotion-focused strategies, except among those who developed PTSD post-COVID-19 infection, presenting with high-stress levels and using more disengagement and emotion-focused types of coping strategies.
Effect of Pholiota nameko Polysaccharides Inhibiting Methylglyoxal-Induced Glycation Damage In Vitro

Advanced glycation end products (AGEs) can induce oxidative stress and inflammation. AGEs are major risk factors for the development of many aging-related diseases, such as cancer and diabetes. In this study, Pholiota nameko polysaccharides (PNPs) were prepared from water extract of P. nameko via graded alcohol precipitation (40%, 60%, and 80% v/v). We explored the in vitro antiglycation ability of the PNPs and inhibition of methylglyoxal (MG)-induced Hs68 cell damage. In a bovine serum albumin (BSA) glycation system, PNPs significantly inhibited the formation of Amadori products. Fluorescence spectrophotometry revealed that the PNPs trapped MG and reduced MG-induced changes in functional groups (carbonyl and ε-NH2) in the BSA. Pretreating Hs68 cells with PNPs enhanced the cell survival rate and protected against MG-induced cell damage. This was due to decreased intracellular ROS content. PNPs thus mitigate skin cell damage and oxidative stress resulting from glycation stress, making them a potential raw material for antiaging-related skincare products.
Pirfenidone Reduces Epithelial–Mesenchymal Transition and Spheroid Formation in Breast Carcinoma through Targeting Cancer-Associated Fibroblasts (CAFs)

Simple Summary Cancer-associated fibroblasts (CAFs) stimulate phenotypic transformation and acquisition of stemness in carcinoma cells. Targeting CAF-derived cytokines may suppress initiation of these events. This study aimed to show the inhibitory effects of pirfenidone on phenotypic transformation and stemness of cancer cells. To this end, we leverage the use of a 3D microfluidic device to analyze carcinoma progression phenotypes. We found that pirfenidone decreased tumor spheroid formation and epithelial–mesenchymal transition (EMT) the inhibition of cytokine production by CAFs. In the microfluidic model, we demonstrate that pirfenidone significantly inhibits the migration of carcinoma cells and CAFs. This study highlights the potential application of pirfenidone in suppressing invasion and potentially metastasis in breast cancer which can be further investigated in vivo. Abstract The aim of this study was to assess the effects of pirfenidone (PFD) on promoting epithelial–mesenchymal-transition (EMT) and stemness features in breast carcinoma cells through targeting cancer-associated-fibroblasts (CAFs). Using The Cancer Genome Atlas (TCGA) database, we analyzed the association between stromal index, EMT, and stemness-related genes across 1084 breast cancer patients, identifying positive correlation between YAP1, EMT, and stemness genes in samples with a high-stromal index. We monitored carcinoma cell invasion and spheroid formation co-cultured with CAFs in a 3D microfluidic device, followed by exposing carcinoma cells, spheroids, and CAFs with PFD. We depicted a positive association between the high-stromal index and the expression of EMT and stemness genes. High YAP1 expression in samples correlated with more advanced EMT status and stromal index. Additionally, we found that CAFs promoted spheroid formation and induced the expression of YAP1, VIM, and CD44 in spheroids. Treatment with PFD reduced carcinoma cell migration and decreased the expression of these genes at the protein level. The cytokine profiling showed significant depletion of various EMT- and stemness-regulated cytokines, particularly IL8, CCL17, and TNF-beta. These data highlight the potential application of PFD on inhibiting EMT and stemness in carcinoma cells through the targeting of critical cytokines.
Fifty Shades of Scandium: Comparative Study of PET Capabilities Using Sc-43 and Sc-44 with Respect to Conventional Clinical Radionuclides

Scandium-44 has been proposed as a valuable radionuclide for Positron Emission Tomography (PET). Recently, scandium-43 was introduced as a more favorable option, as it does not emit high-energy γ-radiation; however, its currently employed production method results in a mixture of scandium-43 and scandium-44. The interest in new radionuclides for diagnostic nuclear medicine critically depends on the option for image-based quantification. We aimed to evaluate and compare the quantitative capabilities of scandium-43/scandium-44 in a commercial PET/CT device with respect to more conventional clinical radionuclides (fluorine-18 and gallium-68). With this purpose, we characterized and compared quantitative PET data from a mixture of scandium-43/scandium-44 (~68% scandium-43), scandium-44, fluorine-18 and gallium-68, respectively. A NEMA image-quality phantom was filled with the different radionuclides using clinical-relevant lesion-to-background activity concentration ratios; images were acquired in a Siemens Biograph Vision PET/CT. Quantitative accuracy with scandium-43/scandium-44 in the phantom’s background was within 9%, which is in agreement with fluorine-18-based PET standards. Coefficient of variance (COV) was 6.32% and signal recovery in the lesions provided RCmax (recovery coefficient) values of 0.66, 0.90, 1.03, 1.04, 1.12 and 1.11 for lesions of 10-, 13-, 17-, 22-, 28- and 37-mm diameter, respectively. These results are in agreement with EARL reference values for fluorine-18 PET. The results in this work showed that accurate quantitative scandium-43/44 PET/CT is achievable in commercial devices. This may promote the future introduction of scandium-43/44-labelled radiopharmaceuticals into clinical use.
A Rare Case of Three Distinct Gastrointestinal Neoplasms Occurring Simultaneously in an Elderly Patient

Duodenal adenocarcinoma (DA), gastrointestinal stromal tumor (GIST), and pancreatic neuroendocrine tumor (PNET) are a set of rare gastrointestinal (GI) cancers characterized by nonspecific symptoms such as anemia, weight loss, and abdominal pain. We report an interesting case of DA, GIST, and PNET in a 79-year-old African American male who presented to the emergency department with syncope. The patient was tachycardic and found to have severe anemia. Further computed tomography (CT) of the abdomen and pelvis with contrast revealed a mass within the duodenal bulb along with a pancreatic cystic lesion. The patient underwent gastroduodenectomy and distal pancreatectomy with incidental findings of GIST in the posterior gastric wall. The patient after surgical removal of all tumors no longer experienced abdominal pain and had hematocrit and hemoglobin (H&H) level of 9.1/31.7 postoperation day (POD) 14. The case unfolds a rare presentation of three neoplasms that were moderate to well-differentiated with no metastases. It highlights the importance of assessment of rare GI neoplasms concurrently with colorectal cancer when geriatric patients present with nonspecific GI symptoms.
A Systems Approach to Interrogate Gene Expression Patterns in African American Men Presenting with Clinically Localized Prostate Cancer

Simple Summary Men of African origin have a 2–3 times greater chance of developing prostate cancer than those of European origin, and of patients that are diagnosed with the disease, men of African descent are 2 times more likely to die compared to white men. Men of African origin are still greatly underrepresented in genetic studies and clinical trials. This, unfortunately, means that new discoveries in cancer treatment are missing key information on the group with a greater chance of mortality. The objective of this study was to increase our knowledge of prostate cancer in men undergoing a prostate biopsy. We carried out RNA sequencing of biopsy specimens and examined racial differences in prostate gene expression. A gene expression signature was uncovered which separated the men based on their race. Furthermore, within men of African descent this signature separated men with the most severe clinical characteristics. Abstract An emerging theory about racial differences in cancer risk and outcomes is that psychological and social stressors influence cellular stress responses; however, limited empirical data are available on racial differences in cellular stress responses among men who are at risk for adverse prostate cancer outcomes. In this study, we undertook a systems approach to examine molecular profiles and cellular stress responses in an important segment of African American (AA) and European American (EA) men: men undergoing prostate biopsy. We assessed the prostate transcriptome with a single biopsy core via high throughput RNA sequencing (RNA-Seq). Transcriptomic analyses uncovered impacted biological pathways including PI3K-Akt signaling pathway, Neuroactive ligand-receptor interaction pathway, and ECM-receptor interaction. Additionally, 187 genes mapping to the Gene Ontology (GO) terms RNA binding, structural constituent of ribosome, SRP-dependent co-translational protein targeting to membrane and the biological pathways, translation, L13a-mediated translational silencing of Ceruloplasmin expression were differentially expressed (DE) between EA and AA. This signature allowed separation of AA and EA patients, and AA patients with the most severe clinical characteristics. AA patients with elevated expression levels of this genomic signature presented with higher Gleason scores, a greater number of positive core biopsies, elevated dehydroepiandrosterone sulfate levels and serum vitamin D deficiency. Protein-protein interaction (PPI) network analysis revealed a high degree of connectivity between these 187 proteins.
The Effect of Trans Fatty Acids on Human Health: Regulation and Consumption Patterns

Health effects of trans fatty acids (TFAs) on human organisms can vary according to their type, structure, composition, and origin. Even though the adverse health effects of industrial TFAs (iTFAs) have been widely discussed, the health effects of natural TFAs (nTFAs) are still questionable. Hence, it is important to review the literature and provide an overall picture on the health effects of different TFAs coming from industrial and ruminant sources, underlining those types that have adverse health effects as well as suggesting methods for reducing their harmful effects. Multiple databases (PubMed, Medline, Cochrane Library, etc.) were searched with the key words “trans fatty acid sources”, “ruminant”, “industrial”, “conjugated trans linoleic acid”, “human”, “coronary heart disease”, “cancer”, etc. Reference lists of the studies were scanned discussing the health effects of iTFAs and nTFAs. The review of the literature showed that iTFAs are found to be more harmful than ruminant-produced nTFAs. Although several beneficial effects (such as reduced risk of diabetes) for nTFAs have been observed, they should be used with caution. Since during labeling it is usually not mentioned whether the TFAs contained in food are of industrial or natural origin, the general suggestion is to reduce their consumption.
More Than a Moggy; A Population Genetics Analysis of the United Kingdom’s Non-Pedigree Cats

The domestic cat is one of the most popular pets in the world. It is estimated that 89–92% of domestic cats in the UK are non-pedigree Domestic shorthair (DSH), Domestic longhair (DLH), or Domestic semi-longhair cats (DSLH). Despite their popularity, little is known of the UK non-pedigree cats’ population structure and breeding dynamics. Using a custom designed single nucleotide variant (SNV) array, this study investigated the population genetics of 1344 UK cats. Principal components analysis (PCA) and fastSTRUCTURE analysis verified that the UK’s DSH, DLH, and DSLH cats are random-bred, rather than admixed, mix breed, or crossbred. In contrast to pedigree cats, the linkage disequilibrium of these random-bred cats was least extensive and decayed rapidly. Homozygosity by descent (HBD) analysis showed the majority of non-pedigree cats had proportionally less of their genome in HBD segments compared to pedigree cats, and that these segments were older. Together, these findings suggest that the DSH, DLH, and DSLH cats should be considered as a population of random-bred cats rather than a crossbred or pedigree-admixed cat. Unexpectedly, 19% of random-bred cat genomes displayed a higher proportion of HBD segments associated with more recent inbreeding events. Therefore, while non-pedigree cats as a whole are genetically diverse, they are not impervious to inbreeding and its health risks.
Large-Scale Non-Targeted Metabolomics Reveals Antioxidant, Nutraceutical and Therapeutic Potentials of Sorghum

Sorghum is one of the most important food and feed cereal crops and has been gaining industrial importance in recent years for its biofuel, nutraceutical and antioxidant values. A genetic profile variation study was undertaken for the accumulation of phytochemicals in 61 diverse sorghum accessions differing in their growth habitat and grain color through non-targeted Gas Chromatography–Mass Spectrometry (GC-MS/MS) analysis. Mass Spectrometry–Data Independent AnaLysis (MS-DIAL) and MetaboAnalyst identified 221 metabolites belonging to 27 different phytochemicals. Tropical and temperate sorghums were distinct in their metabolic profiles with minimum overlaps, and 51 different metabolites were crucial in differentiating the two groups. Temperate sorghums had the ability to accumulate more of phenolic acids, phytosterols, flavonoids, carotenoids, and tropical sorghums for stress-related amino acids, sugars and fatty acids. Grain-color-based Partial Least Square–Discriminant Analysis (PLS-DA) analysis identified 94 Variable Importance in Projections (VIP) metabolites containing majority of flavonoids, phenylpropanoids and phytosterols. This study identified two sorghum lines (IS 7748 and IS 14861) with rich amounts of antioxidants (catechins and epicatechins) belonging to the group of condensed tannins that otherwise do not accumulate commonly in sorghum. Out of 13 metabolic pathways identified, flavonoid biosynthesis showed the highest expression. This study provided new opportunities for developing biofortified sorghum with enhanced nutraceutical and therapeutics through molecular breeding and metabolic engineering.
NBD2 Is Required for the Rescue of Mutant F508del CFTR by a Thiazole-Based Molecule: A Class II Corrector for the Multi-Drug Therapy of Cystic Fibrosis

Cystic fibrosis (CF) is caused by loss-of-function mutations in the CF transmembrane conductance regulator (CFTR) protein, an anion channel that regulates epithelial surface fluid secretion. The deletion of phenylalanine at position 508 (F508del) is the most common CFTR mutation. F508del CFTR is characterized by folding and trafficking defects, resulting in decreased functional expression of the protein on the plasma membrane. Several classes of small molecules, named correctors, have been developed to rescue defective F508del CFTR. Although individual correctors failed to improve the clinical status of CF patients carrying the F508del mutation, better results were obtained using correctors combinations. These results were obtained according to the premise that the administration of correctors having different sites of action should enhance F508del CFTR rescue. We investigated the putative site of action of an aminoarylthiazole 4-(3-chlorophenyl)-N-(3-(methylthio)phenyl)thiazol-2-amine, named FCG, with proven CFTR corrector activity, and its synergistic effect with the corrector VX809. We found that neither the total expression nor the maturation of WT CFTR transiently expressed in human embryonic kidney 293 cells was influenced by FCG, administrated alone or in combination with VX809. On the contrary, FCG was able to enhance F508del CFTR total expression, and its combination with VX809 provided a further effect, being able to increase not only the total expression but also the maturation of the mutant protein. Analyses on different CFTR domains and groups of domains, heterologously expressed in HEK293 cells, show that NBD2 is necessary for FCG corrector activity. Molecular modelling analyses suggest that FCG interacts with a putative region located into the NBD2, ascribing this molecule to class II correctors. Our study indicates that the continuous development and testing of combinations of correctors targeting different structural and functional defects of mutant CFTR is the best strategy to ensure a valuable therapeutic perspective to a larger cohort of CF patients.
Heritability and De Novo Mutations in Oesophageal Atresia and Tracheoesophageal Fistula Aetiology

Tracheoesophageal Fistula (TOF) is a congenital anomaly for which the cause is unknown in the majority of patients. OA/TOF is a variable feature in many (often mono-) genetic syndromes. Research using animal models targeting genes involved in candidate pathways often result in tracheoesophageal phenotypes. However, there is limited overlap in the genes implicated by animal models and those found in OA/TOF-related syndromic anomalies. Knowledge on affected pathways in animal models is accumulating, but our understanding on these pathways in patients lags behind. If an affected pathway is associated with both animals and patients, the mechanisms linking the genetic mutation, affected cell types or cellular defect, and the phenotype are often not well understood. The locus heterogeneity and the uncertainty of the exact heritability of OA/TOF results in a relative low diagnostic yield. OA/TOF is a sporadic finding with a low familial recurrence rate. As parents are usually unaffected, de novo dominant mutations seems to be a plausible explanation. The survival rates of patients born with OA/TOF have increased substantially and these patients start families; thus, the detection and a proper interpretation of these dominant inherited pathogenic variants are of great importance for these patients and for our understanding of OA/TOF aetiology.
Lactobacillus rhamnosus Probio-M9 Improves the Quality of Life in Stressed Adults by Gut Microbiota

Objective: To evaluate the effect of the probiotic, Lactobacillus rhamnosus Probio-M9 (Probio-M9), on the quality of life in stressed adults. Methods: Twelve postgraduate student volunteers were recruited. Six volunteers received oral Probio-M9 for 21 days, while the remaining six received a placebo instead. Fecal samples were collected from the volunteers before and after the intervention. Metagenomic sequencing, nontargeted metabonomics, and quality-of-life follow-up questionnaires were used to evaluate the impact of Probio-M9 consumption on the gut microbiota and life quality of the volunteers. Results: Probio-M9 improved the psychological and physiological quality-of-life symptoms significantly in stressed adults (p < 0.05). The probiotic intervention was beneficial in increasing and maintaining the diversity of gut microbiota. The abundance of Barnesiella and Akkermansia increased in the probiotics group. The feature metabolites of pyridoxamine, dopamine, and 5-hydroxytryptamine (5-HT) were positively correlated with Barnesiella and Akkermansia levels, which might be why the mental state of the volunteers in the probiotic group improved after taking Probio-M9. Conclusions: We identified that oral Probio-M9 can regulate the stability of gut microbiota and affect the related beneficial metabolites, thereby affecting the quality of life (QoL) of stressed adults. Probio-M9 might improve the psychological and physiological quality of life in stressed adults via the gut-brain axis pathway. The causal relationship should be further explored in future studies.