Miracle-dz/UniFAR-FTUs huggingface dataset:
Global Methylome Scores Correlate with Histological Subtypes of Colorectal Carcinoma and Show Different Associations with Common Clinical and Molecular Features

Simple Summary Aberrant patterns of methylation at specific genome sequences (CpG) are driving forces for the carcinogenesis process of different cancers, including colorectal cancer (CRC) and, typically, include gene promoter hypermethylation and global genome hypomethylation. Despite that CRC is diagnosed based on histological evaluation, its association with global methylation patterns has not been established so far. By studying the methylation status of 450,000 CpG sites in 117 colorectal specimens, the authors obtained global scores reflecting the methylation level at different sequence distances from the genes. The authors identified that histological CRC subtypes show different global methylation scores and that the shift from promoter hypermethylation to genomic hypomethylation occurs at a small sequence between 250 bp and 1 Kb from the gene TSS. Abstract Background. The typical methylation patterns associated with cancer are hypermethylation at gene promoters and global genome hypomethylation. Aberrant CpG island hypermethylation at promoter regions and global genome hypomethylation have not been associated with histological colorectal carcinomas (CRC) subsets. Using Illumina’s 450 k Infinium Human Methylation beadchip, the methylome of 82 CRCs were analyzed, comprising different histological subtypes: 40 serrated adenocarcinomas (SAC), 32 conventional carcinomas (CC) and 10 CRCs showing histological and molecular features of microsatellite instability (hmMSI-H), and, additionally, 35 normal adjacent mucosae. Scores reflecting the overall methylation at 250 bp, 1 kb and 2 kb from the transcription starting site (TSS) were studied. Results. SAC has an intermediate methylation pattern between CC and hmMSI-H for the three genome locations. In addition, the shift from promoter hypermethylation to genomic hypomethylation occurs at a small sequence between 250 bp and 1 Kb from the gene TSS, and an asymmetric distribution of methylation was observed between both sides of the CpG islands (N vs. S shores). Conclusion. These findings show that different histological subtypes of CRC have a particular global methylation pattern depending on sequence distance to TSS and highlight the so far underestimated importance of CpGs aberrantly hypomethylated in the clinical phenotype of CRCs.
Machine Learning to Detect Posture and Behavior in Dairy Cows: Information from an Accelerometer on the Animal’s Left Flank

Simple Summary This study analyzed the possibility of automatically detecting dairy cow behavior by combining the use of a single triaxial accelerometer applied to the animal’s left flank with a machine learning technique. This combination enabled the detection of posture and the main types of behavior that are extremely useful in evaluating the animal’s welfare and health such as resting, feeding, and rumination with a high degree of accuracy. The novelty of the study was the success in reaching a high accuracy in detecting five different behaviors and the animal posture by using a single sensor and allowing farmers to save money. To the best of our knowledge, this is the first study that has successfully explored the feasibility of locating a sensor on the animal’s left flank, showing the opportunity of automatically measuring some physiological parameters, such as those ones related to respiration and rumen health, in a non-invasive way. Abstract The aim of the present study was to develop a model to identify posture and behavior from data collected by a triaxial accelerometer located on the left flank of dairy cows and evaluate its accuracy and precision. Twelve Italian Red-and-White lactating cows were equipped with an accelerometer and observed on average for 136 ± 29 min per cow by two trained operators as a reference. The acceleration data were grouped in time windows of 8 s overlapping by 33.0%, for a total of 35,133 rows. For each row, 32 different features were extracted and used by machine learning algorithms for the classification of posture and behavior. To build up a predictive model, the dataset was split in training and testing datasets, characterized by 75.0 and 25.0% of the observations, respectively. Four algorithms were tested: Random Forest, K Nearest Neighbors, Extreme Boosting Algorithm (XGB), and Support Vector Machine. The XGB model showed the best accuracy (0.99) and Cohen’s kappa (0.99) in predicting posture, whereas the Random Forest model had the highest overall accuracy in predicting behaviors (0.76), showing a balanced accuracy from 0.96 for resting to 0.77 for moving. Overall, very accurate detection of the posture and resting behavior were achieved.
Feeling the Heat: The Campylobacter jejuni HrcA Transcriptional Repressor Is an Intrinsic Protein Thermosensor

The heat-shock response, a universal protective mechanism consisting of a transcriptional reprogramming of the cellular transcriptome, results in the accumulation of proteins which counteract the deleterious effects of heat-stress on cellular polypeptides. To quickly respond to thermal stress and trigger the heat-shock response, bacteria rely on different mechanisms to detect temperature variations, which can involve nearly all classes of biological molecules. In Campylobacter jejuni the response to heat-shock is transcriptionally controlled by a regulatory circuit involving two repressors, HspR and HrcA. In the present work we show that the heat-shock repressor HrcA acts as an intrinsic protein thermometer. We report that a temperature upshift up to 42 °C negatively affects HrcA DNA-binding activity to a target promoter, a condition required for de-repression of regulated genes. Furthermore, we show that this impairment of HrcA binding at 42 °C is irreversible in vitro, as DNA-binding was still not restored by reversing the incubation temperature to 37 °C. On the other hand, we demonstrate that the DNA-binding activity of HspR, which controls, in combination with HrcA, the transcription of chaperones’ genes, is unaffected by heat-stress up to 45 °C, portraying this master repressor as a rather stable protein. Additionally, we show that HrcA binding activity is enhanced by the chaperonin GroE, upon direct protein–protein interaction. In conclusion, the results presented in this work establish HrcA as a novel example of intrinsic heat-sensing transcriptional regulator, whose DNA-binding activity is positively modulated by the GroE chaperonin.
Coordination of RNA Processing Regulation by Signal Transduction Pathways

Signal transduction pathways transmit the information received from external and internal cues and generate a response that allows the cell to adapt to changes in the surrounding environment. Signaling pathways trigger rapid responses by changing the activity or localization of existing molecules, as well as long-term responses that require the activation of gene expression programs. All steps involved in the regulation of gene expression, from transcription to processing and utilization of new transcripts, are modulated by multiple signal transduction pathways. This review provides a broad overview of the post-translational regulation of factors involved in RNA processing events by signal transduction pathways, with particular focus on the regulation of pre-mRNA splicing, cleavage and polyadenylation. The effects of several post-translational modifications (i.e., sumoylation, ubiquitination, methylation, acetylation and phosphorylation) on the expression, subcellular localization, stability and affinity for RNA and protein partners of many RNA-binding proteins are highlighted. Moreover, examples of how some of the most common signal transduction pathways can modulate biological processes through changes in RNA processing regulation are illustrated. Lastly, we discuss challenges and opportunities of therapeutic approaches that correct RNA processing defects and target signaling molecules.
Glyoxalase-I Is Upregulated in Acute Cerulein-Induced Pancreatitis: A New Mechanism in Pancreatic Inflammation?

Inflammation caused by oxidative stress (ROS) demonstrates an essential mechanism in the pathogenesis of acute pancreatitis (AP). Important sources for ROS comprise the reactive compound methylglyoxal (MGO) itself and the MGO-derived formation of advanced glycation end-products (AGEs). AGEs bind to the transmembrane receptor RAGE and activate NF-κB, and lead to the production of pro-inflammatory cytokines. MGO is detoxified by glyoxalase-I (Glo-I). The importance of Glo-I was shown in different models of inflammation and carcinogenesis. Nevertheless, the role of Glo-I and MGO in AP has not been evaluated so far. This study analyzed Glo-I in cerulein-(CN)-induced AP and determined the effects of Glo-I knockdown, overexpression and pharmacological modulation. Methods: AP was induced in C57BL6/J mice by i.p. injection of CN. Glo-I was analyzed in explanted pancreata by Western Blot, qRT-PCR and immunohistochemistry. AR42J cells were differentiated by dexamethasone and stimulated with 100 nM of CN. Cells were simultaneously treated with ethyl pyruvate (EP) or S-p-bromobenzylglutathione-cyclopentyl-diester (BrBz), two Glo-I modulators. Knockdown and overexpression of Glo-I was achieved by transient transfection with Glo-I siRNA and pEGFP-N1-Glo-I-Vector. Amylase secretion, TNF-α production (ELISA) and expression of Glo-I, RAGE and NF-κB were measured. Results: Glo-I was significantly upregulated on protein and mRNA levels in CN-treated mice and AR42J cells. Dexamethasone-induced differentiation of AR42J cells increased the expression of Glo-I and RAGE. Treatment of AR42J cells with CN and EP or BrBz resulted in a significant reduction of CN-induced amylase secretion, NF-κB, RAGE and TNF-α. Overexpression of Glo-I led to a significant reduction of CN-induced amylase levels, NF-κB expression and TNF-α, whereas Glo-I knockdown revealed only slight alterations. Measurements of specific Glo-I activity and MGO levels indicated a complex regulation in the model of CN-induced AP. Conclusion: Glo-I is overexpressed in a model of CN-induced AP. Pharmacological modulation and overexpression of Glo-I reduced amylase secretion and the release of pro-inflammatory cytokines in AP in vitro. Targeting Glo-I in AP seems to be an interesting approach for future in vivo studies of AP.
Functionalization of Biotinylated Polyethylene Glycol on Live Magnetotactic Bacteria Carriers for Improved Stealth Properties

Simple Summary The development of new approaches in the field of drug delivery systems is primarily based on increasing the accuracy and precision of the targeted site and improving the stability of the drug by preventing the phagocytosis process inside the body. Among many other methods used to fulfill the above-mentioned requirements, the use of magnetotactic bacteria (MTB) is proven to be a promising solution, as it is self-propelling in nature, and can also be controlled by an external magnetic field. For the present work, we developed an MTB/PEG–biotin complex by exploiting the process of covalent bond formation between bacteria and a biotin–PEG–NHS polymer. In addition to this, attachment efficacy and stability were also determined. In biological applications, cytotoxicity assay of THP-1 cells was performed, showing the MTB/PEG–biotin complex to be less harmful to the cells; meanwhile, to explore the stealth properties of the complex, we performed a cell association assay. With these results, we provide a significant contribution to the field of potential drug delivery system development. Abstract The early removal of drug delivery agents before reaching the affected target remains an area of interest to researchers. Several magnetotactic bacteria (MTB) have been used as self-propelled drug delivery agents, and they can also be controlled by an external magnetic field. By attaching the PEG–biotin polymer, the bacteria are turned into a stealth material that can escape from the phagocytosis process and reach the area of interest with the drug load. In the study, we developed a potential drug carrier by attaching the PEG–biotin to the MTB-through-NHS crosslinker to form a MTB/PEG–biotin complex. The attachment stability, efficacy, and bacterial viability upon attachment of the PEG–biotin polymer were investigated. Biological applications were carried out using a cytotoxicity assay of THP-1 cells, and the results indicate that the MTB/PEG–biotin complex is less harmful to cell viability compared to MTB alone. Along with cytotoxicity, an assay for cell association was also evaluated to assess the complex as a potential stealth material. The development of these complexes focuses on an easy, time-saving, and stable technique of polymer attachment with the bacteria, without damaging the cell’s surface, so as to make it a strong and reliable delivery agent.
Machine Learning Algorithms to Predict Mortality of Neonates on Mechanical Intubation for Respiratory Failure

Background: Early identification of critically ill neonates with poor outcomes can optimize therapeutic strategies. We aimed to examine whether machine learning (ML) methods can improve mortality prediction for neonatal intensive care unit (NICU) patients on intubation for respiratory failure. Methods: A total of 1734 neonates with respiratory failure were randomly divided into training (70%, n = 1214) and test (30%, n = 520) sets. The primary outcome was the probability of NICU mortality. The areas under the receiver operating characteristic curves (AUCs) of several ML algorithms were compared with those of the conventional neonatal illness severity scoring systems including the NTISS and SNAPPE-II. Results: For NICU mortality, the random forest (RF) model showed the highest AUC (0.939 (0.921–0.958)) for the prediction of neonates with respiratory failure, and the bagged classification and regression tree model demonstrated the next best results (0.915 (0.891–0.939)). The AUCs of both models were significantly better than the traditional NTISS (0.836 (0.800–0.871)) and SNAPPE-II scores (0.805 (0.766–0.843)). The superior performances were confirmed by higher accuracy and F1 score and better calibration, and the superior and net benefit was confirmed by decision curve analysis. In addition, Shapley additive explanation (SHAP) values were utilized to explain the RF prediction model. Conclusions: Machine learning algorithms increase the accuracy and predictive ability for mortality of neonates with respiratory failure compared with conventional neonatal illness severity scores. The RF model is suitable for clinical use in the NICU, and clinicians can gain insights and have better communication with families in advance.
The Use of Organic Acids (Lactic and Acetic) as a Microbial Decontaminant during the Slaughter of Meat Animal Species: A Review

Wild ungulate species provide a much-needed protein source to many communities in developed and developing countries. Frequently, these game meat animals are slaughtered, and the meat is unknowingly contaminated by microorganisms and released to the unsuspecting public. This review investigates the global usage of organic acids (lactic and acetic acids) as microbial decontamination strategies during slaughter. The results show that there is a more open-minded approach to adopting possible decontamination plans as a tool to improve meat safety during slaughter. Developed countries continue to adopt these strategies, while developing countries are lagging behind. While decontamination of carcasses can lead to a reduction of microbial load on these carcasses, this strategy must not be seen as a replacement of hygiene management during the animals’ slaughter.
Astrocytes, a Promising Opportunity to Control the Progress of Parkinson’s Disease

At present, there is no efficient treatment to prevent the evolution of Parkinson’s disease (PD). PD is generated by the concurrent activity of multiple factors, which is a serious obstacle for the development of etio-pathogenic treatments. Astrocytes may act on most factors involved in PD and the promotion of their neuroprotection activity may be particularly suitable to prevent the onset and progression of this basal ganglia (BG) disorder. The main causes proposed for PD, the ability of astrocytes to control these causes, and the procedures that can be used to promote the neuroprotective action of astrocytes will be commented upon, here.
Impact of Gluten-Free Sorghum Bread Genotypes on Glycemic and Antioxidant Responses in Healthy Adults

Sorghum is used to provide good quality gluten-free products due to phytochemicals and low glycemic index (GI). This study aimed to determine the chemical composition, the antioxidant activity and capacity, and the glycemic and insulinemic responses of gluten-free (GF) sorghum bread. GF bread samples were produced with three different sorghum genotypes. The samples were analyzed for chemical composition, resistant starch and dietary fiber content; antioxidant activity by ORAC; antioxidant capacity by FRAP; GI; and insulinemic responses. This double-blind, crossover, randomized clinical trial was conducted with 10 healthy men aged 28.0 ± 4.9 years (77.6 ± 11.7 kg and 24.2 ± 2.3 kg/m2). All sorghum bread showed significantly more fiber than rice bread (control). Brown sorghum bread was classified as low GI, bronze and white as medium GI, and control as high GI. Brown sorghum bread presented a low carbohydrate content, a significant amount of fiber, and a significantly lower 3 h AUC glucose response than those of the control, aside from the highest antioxidant activity value (p ≤ 0.001). Therefore, brown sorghum was superior to other genotypes analyzed in this study, and its production should be encouraged to provide gluten-free products with a better nutritional profile. More research is required to explore the effects of different sorghum genotypes in food products on human health.
Potential of Grape Extract in Comparison with Therapeutic Dosage of Antibiotics in Weaning Piglets: Effects on Performance, Digestibility and Microbial Metabolites of the Ileum and Colon

Simple Summary Diarrhea as a symptom of different enteric infections leads to poor animal health and performance at weaning, followed by economic losses. Phytogenic feed additives, e.g., grape extracts, have shown antimicrobial and anti-inflammatory properties and these might have beneficial effects on growth trends of weaning piglets and, thereby, potentially reduce the need for antibiotic treatments following weaning. An 8-week feeding trial investigated the potential effects of grape extract (GE) in a model with a negative control (NC) and positive control (PC; antibiotic treatment). Despite no changes in animal performance, dietary GE improved the digestibility of selected nutrients at the same, or even at higher level, as PC. Additionally, there was no clear effect of dietary intervention on the microbial metabolites from the ileum and colon at the end of the trial. These results indicated beneficial effects of GE compared to antibiotic treatment, as often applied at weaning. Abstract Enteric diseases in piglets, such as post-weaning diarrhea (PWD), often require antibiotic treatment of the entire litter. Grape polyphenols may help overcome PWD and thereby reduce the need for antibiotics. The potential of a grape extract (GE; continuous in-feed supplementation) on performance of weaning piglets, compared with both negative (NC; corn-based diet) and positive control (PC; NC + in-feed antibiotic (amoxicillin) in a therapeutic dosage for day 1–day 5 post weaning) was assessed. Apparent total tract digestibility (ATTD) and microbial metabolites were also evaluated on two sampling points (day 27/28 and day 55/56). We assigned 180 weaning piglets (6.9 ± 0.1 kg body weight (BW)) to 6 male and 6 female pens per treatment with 5 piglets each. Animals from PC showed higher BW on day 13 compared with NC and GE, and a tendency for higher BW on day 56 (p = 0.080) compared to NC. Furthermore, PC increased the average daily feed intake in the starter phase (day 1–day 13), and the average daily gain in the early grower phase (day 14–day 24). Overall, GE improved the ATTD at the same level as PC (ash, acid-hydrolyzed ether extract), or at a higher level than PC (dry matter, organic matter, gross energy, crude protein, P). There were no effects on microbial metabolites apart from minor trends for lactic acid and ammonia. Dietary inclusion of GE may have beneficial effects compared to therapeutic antibiotics, as frequently used at weaning.
Effects of Breaking Methods on the Viscosity, Rheological Properties and Nutritional Value of Tomato Paste

Ultrasound-assisted processing has potential application advantages as an emerging technology for preparing tomato paste. This work explored the influence of ultrasound break at 22 °C (US-Break-22) and 65 °C (US-Break-65) on the viscosity, rheological properties and nutritional values of newly prepared tomato paste, compared with traditional thermal break at 65 °C (Break-65) and 90 °C (Break-90). Results showed that the US-Break-65 paste had the largest apparent viscosity, yield stress, consistency coefficient, solid-like nature, and large amplitude oscillatory shear behavior, followed by the US-Break-22 paste, Break-90 paste, and Break-65 paste. Based on the results of the pectin-related enzymes, particle size, and serum pectin of the pastes, it was revealed that the above-mentioned properties were mainly determined by the particle size and pectin content in their serum. The level of ascorbic acid followed the order of US-Break-22 paste > US-Break-65 paste > Break-65 paste > Break-90 paste. The level of total carotenoids followed the order of US-Break-22 paste ≈ US-Break-65 paste > Break-90 paste ≈ Break-65 paste. The level of total cis-carotenoids followed the order of US-Break-65 paste > US-Break-22 paste > Break-90 paste > Break-65 paste. The level of phenolics and antioxidant activities followed the same order of US-Break-22 paste > US-Break-65 paste > Break-90 paste > Break-65 paste. Overall, the viscosity, rheological properties and nutritional values of the tomato pastes prepared by US-Break-65 and US-Break-22 were significantly higher than those prepared by Break-65 and Break-90. Therefore, ultrasound assisted processing can prepare high quality tomato paste and can be widely implemented in the tomato paste processing industry.
A Prospective Cohort Study on Quality of Life among the Pediatric Population after Surgery for Recurrent Patellar Dislocation

Patellofemoral instability is a frequent cause of knee pathology affecting quality of life among the pediatric population. Here, we present a prospective cohort study which included patients who had undergone surgical management using the lateral release and medial imbrication approach (LRMI) or medial patellofemoral ligament reconstruction (MPFL-R). The object of this study was to assess the quality of life among children that have undergone surgical treatment for patellar dislocation. Quality of life was assessed before and after surgery using the Pediatric International Knee Documentation Committee form (Pedi-IKDC), a questionnaire that aims to quantify knee functionality. Postoperative scarring was evaluated using The Stony Brook Scar Evaluation Scale. One hundred and eight patients were selected and grouped according to the type of procedure. Before surgery, the two groups had similar mean Pedi-IKDC scores (41,4 MPFL-R vs. 39,4 LRMI p = 0.314). Improvements were observed in the postoperative scores. The MPFL-R technique showed promising outcomes. When comparing the two surgical groups, there was a significant difference in favor of MPFL-R group (MPFL-R 77.71 points vs. LRMI 59.74 points, p < 0.0001–95% CI (11.22–24.72)). Using the Stony Brook Scar Evaluation Scale, a significant difference in scar quality in favor of MPFL-R was observed (4,5 MPFL-R vs. 2,77 LRMI p = 0.002). In conclusion, this study provides objective evidence-based outcome assessments that support the medial patellofemoral ligament reconstruction technique as the gold standard for patellofemoral instability.