Miracle-dz/UniFAR-FTUs huggingface dataset:
Gallbladder Polyp Classification in Ultrasound Images Using an Ensemble Convolutional Neural Network Model

Differential diagnosis of true gallbladder polyps remains a challenging task. This study aimed to differentiate true polyps in ultrasound images using deep learning, especially gallbladder polyps less than 20 mm in size, where clinical distinction is necessary. A total of 501 patients with gallbladder polyp pathology confirmed through cholecystectomy were enrolled from two tertiary hospitals. Abdominal ultrasound images of gallbladder polyps from these patients were analyzed using an ensemble model combining three convolutional neural network (CNN) models and a 5-fold cross-validation. True polyp diagnosis with the ensemble model that learned only using ultrasonography images achieved an area under receiver operating characteristic curve (AUC) of 0.8960 and accuracy of 83.63%. After adding patient age and polyp size information, the diagnostic performance of the ensemble model improved, with a high specificity of 88.35%, AUC of 0.9082, and accuracy of 87.61%, outperforming the individual CNN models constituting the ensemble model. In the subgroup analysis, the ensemble model showed the best performance with AUC of 0.9131 for polyps larger than 10 mm. Our proposed ensemble model that combines three CNN models classifies gallbladder polyps of less than 20 mm in ultrasonography images with high accuracy and can be useful for avoiding unnecessary cholecystectomy with high specificity.
Synthesis, DFT Calculations, Antiproliferative, Bactericidal Activity and Molecular Docking of Novel Mixed-Ligand Salen/8-Hydroxyquinoline Metal Complexes

Despite the common use of salens and hydroxyquinolines as therapeutic and bioactive agents, their metal complexes are still under development. Here, we report the synthesis of novel mixed-ligand metal complexes (MSQ) comprising salen (S), derived from (2,2′-{1,2-ethanediylbis[nitrilo(E) methylylidene]}diphenol, and 8-hydroxyquinoline (Q) with Co(II), Ni(II), Cd(II), Al(III), and La(III). The structures and properties of these MSQ metal complexes were investigated using molar conductivity, melting point, FTIR, 1H NMR, 13C NMR, UV–VIS, mass spectra, and thermal analysis. Quantum calculation, analytical, and experimental measurements seem to suggest the proposed structure of the compounds and its uncommon monobasic tridentate binding mode of salen via phenolic oxygen, azomethine group, and the NH group. The general molecular formula of MSQ metal complexes is [M(S)(Q)(H2O)] for M (II) = Co, Ni, and Cd or [M(S)(Q)(Cl)] and [M(S)(Q)(H2O)]Cl for M(III) = La and Al, respectively. Importantly, all prepared metal complexes were evaluated for their antimicrobial and anticancer activities. The metal complexes exhibited high cytotoxic potency against human breast cancer (MDA-MB231) and liver cancer (Hep-G2) cell lines. Among all MSQ metal complexes, CoSQ and LaSQ produced IC50 values (1.49 and 1.95 µM, respectively) that were comparable to that of cisplatin (1.55 µM) against Hep-G2 cells, whereas CdSQ and LaSQ had best potency against MDA-MB231 with IC50 values of 1.95 and 1.43 µM, respectively. Furthermore, the metal complexes exhibited significant antimicrobial activities against a wide spectrum of both Gram-positive and -negative bacterial and fungal strains. The antibacterial and antifungal efficacies for the MSQ metal complexes, the free S and Q ligands, and the standard drugs gentamycin and ketoconazole decreased in the order AlSQ > LaSQ > CdSQ > gentamycin > NiSQ > CoSQ > Q > S for antibacterial activity, and for antifungal activity followed the trend of LaSQ > AlSQ > CdSQ > ketoconazole > NiSQ > CoSQ > Q > S. Molecular docking studies were performed to investigate the binding of the synthesized compounds with breast cancer oxidoreductase (PDB ID: 3HB5). According to the data obtained, the most probable coordination geometry is octahedral for all the metal complexes. The molecular and electronic structures of the metal complexes were optimized theoretically, and their quantum chemical parameters were calculated. PXRD results for the Cd(II) and La(III) metal complexes indicated that they were crystalline in nature.
Comparison of Bovine Mammary Involution and Intramammary Infections Following Intramammary Treatment with Casein Hydrolysate and Other Conventional Treatments at Dry-Off

Simple Summary Alternatives to antibiotic therapy for mastitis in dairy cattle are of interest to the dairy industry and society. Reduced use of antibiotics while maintaining or improving animal welfare is desirable. We studied the intramammary infusion of casein hydrolysate, alone or combined with standard dry cow treatment, at the beginning of the dry period before cows have their next calf. The effects on mammary involution and milk quality suggested that infusion of casein hydrolysate alone or combined with internal teat sealant may be an alternative to antibiotic dry cow therapy. Abstract Alternatives to routine antibiotic treatment of dairy cattle during the dry period before their next calving are of interest. This was a preliminary study of whether intramammary infusion of casein hydrolysate, administered alone or combined with standard dry treatment, accelerated the rate of mammary involution early in the dry period. Four treatments were studied in a split udder design. One udder half was assigned a treatment, and the contralateral half was administered dry cow treatment + internal teat sealant as a control. Treatments were casein hydrolysate, casein hydrolysate + dry cow treatment, casein hydrolysate + teat sealant and casein hydrolysate + dry cow treatment + teat sealant. Cows (n = 16) were blocked by a number of intramammary infections per udder half (0 or 1+) and randomized to treatments. Milk production was not different between control or treated udder halves post-calving. A generalized linear mixed model tested for differences between the treatment groups in the concentration of mammary involution indicators in milk: somatic cell count, bovine lactoferrin and bovine serum albumin. At 7 days, dry udder halves treated with casein hydrolysate had higher milk concentrations of lactoferrin than those treated with casein hydrolysate + dry cow treatment, casein hydrolysate + teat sealant and control. At 10 days dry, bovine serum albumin was higher in udder halves treated with casein hydrolysate than in those treated with casein hydrolysate + dry cow treatment, casein hydrolysate + dry cow treatment + teat sealant and control. Post-calving, casein hydrolysate-treated udder halves produced 51% of total milk, unchanged from before dry-off. There were seven total intramammary infections entering the dry period, all caused by coagulase-negative staphylococci. Cure rates (3/7, 43%) were not different among all treatments and control, partly because of the small sample size. Intramammary infusion of casein hydrolysate at the end of lactation may be an alternative or possible adjunct to antibiotic dry cow therapy.
Role of Inflammatory Mediators, Macrophages, and Neutrophils in Glioma Maintenance and Progression: Mechanistic Understanding and Potential Therapeutic Applications

Simple Summary The tumor microenvironment is a complex network comprised of neoplastic and a variety of immune cells, proteins, and inflammatory mediators. Previous studies have shown that during cancer progression, diverse inflammatory molecules, either directly or indirectly via recruiting immune cells, support the process of carcinogenesis. The present review focuses on the mechanistic understanding of the oncogenic role of these inflammatory mediators and immune cells, particularly tumor-associated macrophages (TAMs) and tumor-associated neutrophils (TANs) in glioma maintenance and progression. Moreover, the potential therapeutic benefits of targeting inflammatory mediators, immune cells, and associated signaling pathways in glioma genesis have also been discussed. Abstract Gliomas are the most common, highly malignant, and deadliest forms of brain tumors. These intra-cranial solid tumors are comprised of both cancerous and non-cancerous cells, which contribute to tumor development, progression, and resistance to the therapeutic regimen. A variety of soluble inflammatory mediators (e.g., cytokines, chemokines, and chemotactic factors) are secreted by these cells, which help in creating an inflammatory microenvironment and contribute to the various stages of cancer development, maintenance, and progression. The major tumor infiltrating immune cells of the tumor microenvironment include TAMs and TANs, which are either recruited peripherally or present as brain-resident macrophages (microglia) and support stroma for cancer cell expansion and invasion. These cells are highly plastic in nature and can be polarized into different phenotypes depending upon different types of stimuli. During neuroinflammation, glioma cells interact with TAMs and TANs, facilitating tumor cell proliferation, survival, and migration. Targeting inflammatory mediators along with the reprogramming of TAMs and TANs could be of great importance in glioma treatment and may delay disease progression. In addition, an inhibition of the key signaling pathways such as NF-κB, JAK/STAT, MAPK, PI3K/Akt/mTOR, and TLRs, which are activated during neuroinflammation and have an oncogenic role in glioblastoma (GBM), can exert more pronounced anti-glioma effects.
A Binary Logistic Regression Model as a Tool to Predict Craft Beer Susceptibility to Microbial Spoilage

Beer spoilage caused by microorganisms, which is a major concern for brewers, produces undesirable aromas and flavors in the final product and substantial financial losses. To address this problem, brewers need easy-to-apply tools that inform them of beer susceptibility to the microbial spoilage. In this study, a growth/no growth (G/NG) binary logistic regression model to predict this susceptibility was developed. Values of beer physicochemical parameters such as pH, alcohol content (% ABV), bitterness units (IBU), and yeast-fermentable extract (% YFE) obtained from the analysis of twenty commercially available craft beers were used to prepare 22 adjusted beers at different levels of each parameter studied. These preparations were assigned as a first group of samples, while 17 commercially available beers samples as a second group. The results of G/NG from both groups, after artificially inoculating with one wild yeast and different lactic acid bacteria (LAB) previously adapted to grow in a beer-type beverage, were used to design the model. The developed G/NG model correctly classified 276 of 331 analyzed cases and its predictive ability was 100% in external validation. This G/NG model has good sensitivity and goodness of fit (87% and 83.4%, respectively) and provides the potential to predict craft beer susceptibility to microbial spoilage.
Childhood Trauma, the Combination of MAO-A and COMT Genetic Polymorphisms and the Joy of Being Aggressive in Forensic Psychiatric Patients

Aggression and violent offenses are common amongst forensic psychiatric patients. Notably, research distinguishes two motivationally distinct dimension of aggression–instrumental and reactive aggression. Instrumental aggression comprises of appetitive, goal-directed aggressive acts, whereas reactive aggression consists of affective, defensive violence with both their biological basis remaining largely unknown. Childhood trauma and functional genetic polymorphisms in catecholamines converting enzymes, such as mono-amino-oxidase A (MAO-A) and catechol-o-methyltransferase (COMT) have been suggested to augment an aggressive behavioral response in adulthood. However, it warrants clarification if these factors influence one or both types of aggression. Furthermore, it remains elusive, if having a combination of unfavorable enzyme genotypes and childhood maltreatment further increases violent behavior. Hence, we set out to address these questions in the current study. First, analysis revealed an overall marginally increased frequency of the unfavorable MAO-A genotype in the test population. Second, each gene polymorphisms together with a traumatic childhood significantly increased the AFAS (Appetitive and Facilitative Aggression Scale) scores for both reactive and appetitive aggression. Third, having a combination of both disadvantageous genotypes and a negative childhood served as a minor positive predictor for increased reactive aggression, but had a strong influence on the joy of being aggressive.
Evaluating, Filtering and Clustering Genetic Disease Cohorts Based on Human Phenotype Ontology Data with Cohort Analyzer

Exhaustive and comprehensive analysis of pathological traits is essential to understanding genetic diseases, performing precise diagnosis and prescribing personalized treatments. It is particularly important for disease cohorts, as thoroughly detailed phenotypic profiles allow patients to be compared and contrasted. However, many disease cohorts contain patients that have been ascribed low numbers of very general and relatively uninformative phenotypes. We present Cohort Analyzer, a tool that measures the phenotyping quality of patient cohorts. It calculates multiple statistics to give a general overview of the cohort status in terms of the depth and breadth of phenotyping, allowing us to detect less well-phenotyped patients for re-examining or excluding from further analyses. In addition, it performs clustering analysis to find subgroups of patients that share similar phenotypic profiles. We used it to analyse three cohorts of genetic diseases patients with very different properties. We found that cohorts with the most specific and complete phenotypic characterization give more potential insights into the disease than those that were less deeply characterised by forming more informative clusters. For two of the cohorts, we also analysed genomic data related to the patients, and linked the genomic data to the patient-subgroups by mapping shared variants to genes and functions. The work highlights the need for improved phenotyping in this era of personalized medicine. The tool itself is freely available alongside a workflow to allow the analyses shown in this work to be applied to other datasets.
Different Patterns of mRNA Nuclear Retention during Meiotic Prophase in Larch Microsporocytes

Recent studies show a crucial role of post-transcriptional processes in the regulation of gene expression. Our research has shown that mRNA retention in the nucleus plays a significant role in such regulation. We studied larch microsporocytes during meiotic prophase, characterized by pulsatile transcriptional activity. After each pulse, the transcriptional activity is silenced, but the transcripts synthesized at this time are not exported immediately to the cytoplasm but are retained in the cell nucleus and especially in Cajal bodies, where non-fully-spliced transcripts with retained introns are accumulated. Analysis of the transcriptome of these cells and detailed analysis of the nuclear retention and transport dynamics of several mRNAs revealed two main patterns of nuclear accumulation and transport. The majority of studied transcripts followed the first one, consisting of a more extended retention period and slow release to the cytoplasm. We have shown this in detail for the pre-mRNA and mRNA encoding RNA pol II subunit 10. In this pre-mRNA, a second (retained) intron is posttranscriptionally spliced at a precisely defined time. Fully mature mRNA is then released into the cytoplasm, where the RNA pol II complexes are produced. These proteins are necessary for transcription in the next pulse to occur.mRNAs encoding translation factors and SERRATE followed the second pattern, in which the retention period was shorter and transcripts were rapidly transferred to the cytoplasm. The presence of such a mechanism in various cell types from a diverse range of organisms suggests that it is an evolutionarily conserved mechanism of gene regulation.
Quality of Fish-Oil-Based Dietary Supplements Available on the Italian Market: A Preliminary Study

The global market of food supplements is growing rapidly with a large turnover. Fish oil supplements represent a significant part of this turnover as they are believed to have important health benefits. Conversely, there are few papers in the literature about the quality control of fish oil capsules. As prior studies illustrate, a perfect agreement with the label is rarely found, and in some isolated cases, large amounts of soybean oil are also detected, indicating a true adulteration rather than a non-compliance with the label. None of the available studies refer to the Italian market, which ranks first in Europe in the consumption of food supplements. In this present communication, a quality control of fish-oil-based supplements from the Italian market was carried out for the first time. With minor deviations, all results showed substantial agreement with the label. However, the most important conclusion from this research is that compliance with the label is not enough to judge a product of good quality. The analysis of the overall fatty acid composition showed that some supplements have a high level of saturated fatty acids, and therefore they did not undergo a proper purification process. This may represent a safety issue since the purification process also allows the removal of toxic contaminants.
The Chemically-Modified Tetracycline COL-3 and Its Parent Compound Doxycycline Prevent Microglial Inflammatory Responses by Reducing Glucose-Mediated Oxidative Stress

We used mouse microglial cells in culture activated by lipopolysaccharide (LPS) or α-synuclein amyloid aggregates (αSa) to study the anti-inflammatory effects of COL-3, a tetracycline derivative without antimicrobial activity. Under LPS or αSa stimulation, COL-3 (10, 20 µM) efficiently repressed the induction of the microglial activation marker protein Iba-1 and the stimulated-release of the pro-inflammatory cytokine TNF-α. COL-3′s inhibitory effects on TNF-α were reproduced by the tetracycline antibiotic doxycycline (DOX; 50 µM), the glucocorticoid dexamethasone, and apocynin (APO), an inhibitor of the superoxide-producing enzyme NADPH oxidase. This last observation suggested that COL-3 and DOX might also operate themselves by restraining oxidative stress-mediated signaling events. Quantitative measurement of intracellular reactive oxygen species (ROS) levels revealed that COL-3 and DOX were indeed as effective as APO in reducing oxidative stress and TNF-α release in activated microglia. ROS inhibition with COL-3 or DOX occurred together with a reduction of microglial glucose accumulation and NADPH synthesis. This suggested that COL-3 and DOX might reduce microglial oxidative burst activity by limiting the glucose-dependent synthesis of NADPH, the requisite substrate for NADPH oxidase. Coherent with this possibility, the glycolysis inhibitor 2-deoxy-D-glucose reproduced the immunosuppressive action of COL-3 and DOX in activated microglia. Overall, we propose that COL-3 and its parent compound DOX exert anti-inflammatory effects in microglial cells by inhibiting glucose-dependent ROS production. These effects might be strengthened by the intrinsic antioxidant properties of DOX and COL-3 in a self-reinforcing manner.
Bovine Satellite Cells Isolated after 2 and 5 Days of Tissue Storage Maintain the Proliferative and Myogenic Capacity Needed for Cultured Meat Production

Cultured meat is an emerging alternative food technology which aims to deliver a more ethical, sustainable, and healthy muscle-tissue-derived food item compared to conventional meat. As start-up companies are rapidly forming and accelerating this technology, many aspects of this multi-faceted science have still not been investigated in academia. In this study, we investigated if bovine satellite cells with the ability to proliferate and undergo myogenic differentiation could be isolated after extended tissue storage, for the purpose of increasing the practicality for cultured meat production. Proliferation of bovine satellite cells isolated on the day of arrival or after 2 and 5 days of tissue storage were analyzed by metabolic and DNA-based assays, while their myogenic characteristics were investigated using RT-qPCR and immunofluorescence. Extended tissue storage up to 5 days did not negatively affect proliferation nor the ability to undergo fusion and create myosin heavy chain-positive myotubes. The expression patterns of myogenic and muscle-specific genes were also not affected after tissue storage. In fact, the data indicated a positive trend in terms of myogenic potential after tissue storage, although it was non-significant. These results suggest that the timeframe of which viable myogenic satellite cells can be isolated and used for cultured meat production can be greatly extended by proper tissue storage.
The Role of Strigolactones in the Regulation of Root System Architecture in Grapevine (Vitis vinifera L.) in Response to Root-Restriction Cultivation

This study investigated the effects of root-restriction cultivation on the root architecture, endogenous strigolactone (SL) content, and SL-related genes expression in grapevine (Vitis vinifera L.). In addition, we clarified the effects of synthetic SL analog GR24 application on grapevine roots to explore the role of SLs in their development. The results showed that the root architecture changed significantly under root-restriction cultivation. At 40 days after transplantation (DAT), the contents of two types of SLs in roots under root restriction were both significantly lower than that in roots of the control. SL content was significantly positively correlated with the expression levels of VvCCD8 and VvD27, indicating that they play vital roles in SLs synthesis. After GR24 treatment for 20 days, the root length was significantly shorter than in the control. A low concentration (0.1 μM) of GR24 significantly reduced the root diameter and increased the fine-root density, while a high concentration (10 μM) of GR24 significantly reduced the lateral root (LR) length and increased the LR density. Concomitantly, GR24 (0.1 μM) reduced endogenous SL content. After GR24 treatment for 5 days, the total content of two tested SLs was highly positively correlated with the expression levels of VvDAD2, whereas it was highly negatively correlated with VvSMAXL4 at 20 days after GR24 treatment. This study helps to clarify the internal mechanism of root-restriction cultivation affecting the changes in grapevine root architecture, as well as further explore the important role of SLs in the growth of grapevine roots in response to root-restriction treatment.