Miracle-dz/UniFAR-FTUs huggingface dataset:
Licensed Anti-Microbial Drugs Logical for Clinical Trials against Pathogens Currently Suspected in Alzheimer’s Disease

There is now considerable evidence that several infectious agents (viruses, bacteria, or parasites) may play a contributing role in the development of Alzheimer’s disease (AD). The six primary suspects are herpes viruses, spirochetal bacteria, Chlamydia pneumoniae, Porphyromonas gingivalis, mycobacteria, and toxoplasma parasites. Also, some of the antimicrobial and antiviral agents that are used to treat them have shown promise for AD interventions. I describe this evidence and assert it is now time to accelerate clinical trials of these existing drugs, already federally approved, to determine if such treatments can delay, halt, or reverse AD.
Approaches to Integrating Metabolomics and Multi-Omics Data: A Primer

Metabolomics deals with multiple and complex chemical reactions within living organisms and how these are influenced by external or internal perturbations. It lies at the heart of omics profiling technologies not only as the underlying biochemical layer that reflects information expressed by the genome, the transcriptome and the proteome, but also as the closest layer to the phenome. The combination of metabolomics data with the information available from genomics, transcriptomics, and proteomics offers unprecedented possibilities to enhance current understanding of biological functions, elucidate their underlying mechanisms and uncover hidden associations between omics variables. As a result, a vast array of computational tools have been developed to assist with integrative analysis of metabolomics data with different omics. Here, we review and propose five criteria—hypothesis, data types, strategies, study design and study focus— to classify statistical multi-omics data integration approaches into state-of-the-art classes under which all existing statistical methods fall. The purpose of this review is to look at various aspects that lead the choice of the statistical integrative analysis pipeline in terms of the different classes. We will draw particular attention to metabolomics and genomics data to assist those new to this field in the choice of the integrative analysis pipeline.
Gut Microbiome Prolongs an Inhibitory Effect of Korean Red Ginseng on High-Fat-Diet-Induced Mouse Obesity

Although the anti-obesity effect of Korean red ginseng (Panax ginseng Meyer) has been revealed, its underlying mechanisms are not clearly understood. Here, we demonstrate an involvement of gut microbiome in the inhibitory effect of Korean red ginseng on high-fat-diet (HFD)-induced mouse obesity, and further provides information on the effects of saponin-containing red ginseng extract (SGE) and saponin-depleted red ginseng extract (GE). Mice were fed with either SGE or GE every third day for one month, and their food intakes, fat weights, plasma glucose, and insulin and leptin levels were measured. Immunofluorescence assays were conducted to measure pancreatic islet size. Stools from the mice were subjected to metagenomic analysis. Both SGE and GE attenuated HFD-induced gain of body weight, reducing HFD-induced increase of food intakes and fat weights. They also reduced HFD-increased plasma glucose, insulin, and leptin levels, decreased both fasting and postprandial glucose concentrations, and improved both insulin resistance and glucose intolerance. Immunofluorescence assays revealed that they blocked HFD-induced increase of pancreatic islet size. Our pyrosequencing of the 16S rRNA gene V3 region from stools revealed that both SGE and GE modulated HFD-altered composition of gut microbiota. Therefore, we conclude that Korean red ginseng inhibits HFD-induced obesity and diabetes by altering gut microbiome.
Mechanical Stabilization of Alginate Hydrogel Fiber and 3D Constructs by Mussel-Inspired Catechol Modification

Alginate is a representative biocompatible natural polymer with low cost for a variety of biomedical applications, such as wound dressing, drug delivery systems, tissue scaffolds, and 3D bioprinting. Particularly, the rapid and facile gelation of alginate via ionic interactions with divalent cations has been used for in situ 3D hydrogel fiber formation, which is potentially applicable to engineering cell alignment. However, challenges in enhancing the mechanical properties of alginate hydrogel fibers under physiological conditions are unresolved because of their fast dissociation by ion exchange. Herein, we report a stabilization strategy for alginate hydrogel fibers through mussel-inspired catechol chemistry, which involves inter-catechol crosslinking within a few minutes under basic conditions. The fabrication of catechol-tethered alginate hydrogel fibers through wet-spinning enabled the design of mechanically strong 3D constructs consisting of fibers. Catechol-to-quinone oxidation followed by covalent crosslinking enhanced the tensile strength of a single fiber. Additionally, the ‘gluing’ capability of the catechol stabilized the interface among the fibers, thus retaining the shape fidelity of the 3D constructs and encapsulating the cell density during culture. Our findings will be useful for designing bioink materials specialized in fibrous-type tissue scaffolds with mechanical stability.
The Association between Portion Sizes from High-Energy-Dense Foods and Body Composition in European Adolescents: The HELENA Study †

Obesity prevalence has been simultaneously increasing with high consumption of large food portion sizes (PS). However, there is scarce information on PS of energy-dense (ED) foods as a potential risk factor of obesity in adolescents. In the present study, we investigate the association between the PS of the most ED foods and body composition. A sample of 1889 adolescents (54.4% females) from the Healthy Lifestyle in Europe by Nutrition in Adolescence cross-sectional multicenter study (HELENA–CSS) study were included. Most ED foods (e.g., cheese) were selected according to higher fat and/or sugar content and low fiber and water. Linear and ordinal logistic regression models were adjusted for age, physical activity, total energy intake (TEI), and socioeconomic status (SES). Analysis was performed both in those adolescents reporting plausible energy intake according to the approach of Goldberg et al. and in the whole sample. In male plausible reporters, PS from “breakfast cereals” showed a significant and positive association with BMI (β = 0.012; 0.048). PS from “carbonated soft drinks” in males (OR = 1.001; 95% CI 1.000; 1.002) and “bread and rolls” in females (OR = 1.002; 95% CI 1.000; 1.004) were associated with higher probability of having obesity, while “sweet bakery products” were associated with lower probability of having obesity (OR = 0.996; 95% CI 0.991; 0.999) in females. The present study suggests association between PS of ED foods and obesity in European adolescents. Prospective studies are needed to examine the effect of prolonged exposure to large PS and obesity development.
Microsatellite Instability in Colorectal Cancer Liquid Biopsy—Current Updates on Its Potential in Non-Invasive Detection, Prognosis and as a Predictive Marker

Colorectal cancer (CRC) is the third most commonly-diagnosed cancer in the world and ranked second for cancer-related mortality in humans. Microsatellite instability (MSI) is an indicator for Lynch syndrome (LS), an inherited cancer predisposition, and a prognostic marker which predicts the response to immunotherapy. A recent trend in immunotherapy has transformed cancer treatment to provide medical alternatives that have not existed before. It is believed that MSI-high (MSI-H) CRC patients would benefit from immunotherapy due to their increased immune infiltration and higher neo-antigenic loads. MSI testing such as immunohistochemistry (IHC) and PCR MSI assay has historically been a tissue-based procedure that involves the testing of adequate tissue with a high concentration of cancer cells, in addition to the requirement for paired normal tissues. The invasive nature and specific prerequisite of such tests might hinder its application when surgery is not an option or when the tissues are insufficient. The application of next-generation sequencing, which is highly sensitive, in combination with liquid biopsy, therefore, presents an interesting possibility worth exploring. This review aimed to discuss the current body of evidence supporting the potential of liquid biopsy as a tool for MSI testing in CRC.
Possibilities for the Biological Control of Mycotoxins in Food and Feed

Seeking useful biological agents for mycotoxin detoxification has achieved success in the last twenty years thanks to the participation of many multidisciplinary teams. We have recently witnessed discoveries in the fields of bacterial genetics (inclusive of next-generation sequencing), protein encoding, and bioinformatics that have helped to shape the latest perception of how microorganisms/mycotoxins/environmental factors intertwine and interact, so the road is opened for new breakthroughs. Analysis of literature data related to the biological control of mycotoxins indicates the ability of yeast, bacteria, fungi and enzymes to degrade or adsorb mycotoxins, which increases the safety and quality of susceptible crops, animal feed and, ultimately, food of animal origin (milk, meat and eggs) by preventing the presence of residues. Microbial detoxification (transformation and adsorption) is becoming a trustworthy strategy that leaves no or less toxic compounds and contributes to food security. This review summarizes the data and highlights the importance and prospects of these methods.
Shifting the Gears of Metabolic Plasticity to Drive Cell State Transitions in Cancer

Simple Summary Metabolic adaptation by cancer cells is enabled through the rewiring of metabolic processes, thereby allowing them to survive and thrive in diverse tissue microenvironments. It is also exploited to maintain cancer stemness, drive epithelial–mesenchymal transition, and gain therapy resistance. These critical cellular events are pertinent to the various steps of cancer progression. Mechanistic insights into nutrient addiction arising from such metabolic rewiring have revealed therapeutic vulnerabilities that can be exploited as novel treatment modalities or for drug development. This review discusses concepts and principles of metabolic plasticity and highlights current preclinical and clinical strategies aimed at targeting these metabolic derangements. Abstract Cancer metabolism is a hallmark of cancer. Metabolic plasticity defines the ability of cancer cells to reprogram a plethora of metabolic pathways to meet unique energetic needs during the various steps of disease progression. Cell state transitions are phenotypic adaptations which confer distinct advantages that help cancer cells overcome progression hurdles, that include tumor initiation, expansive growth, resistance to therapy, metastasis, colonization, and relapse. It is increasingly appreciated that cancer cells need to appropriately reprogram their cellular metabolism in a timely manner to support the changes associated with new phenotypic cell states. We discuss metabolic alterations that may be adopted by cancer cells in relation to the maintenance of cancer stemness, activation of the epithelial–mesenchymal transition program for facilitating metastasis, and the acquisition of drug resistance. While such metabolic plasticity is harnessed by cancer cells for survival, their dependence and addiction towards certain metabolic pathways also present therapeutic opportunities that may be exploited.
Spread of Influenza Viruses in Poland and Neighboring Countries in Seasonal Terms

In Poland, flu supervision is coordinated by the National Influenza Center at the National Institute of Public Health—National Institute of Hygiene. In this publication, we want to determine geographical trends in influenza virus circulation in the region. A detailed analysis of virological and epidemiological data showed the course of the epidemic season in Poland, as well as in neighboring countries. The spatial differentiation of the incidence of infection between voivodships was examined, as well as compared to countries that border a given voivodship. The results show a significant variation in the incidence of infection in terms of time and space. This points to the need to increase the number of tests and to raise awareness among health care professionals and the public about the probability of an influenza pandemic, as undetected viruses can spread further into the European Union.
Thin-Film Composite Nanofiltration Membranes for Non-Polar Solvents

Organic solvent nanofiltration (OSN) has been recognized as an eco-friendly separation system owing to its excellent cost and energy saving efficiency, easy scale-up in the narrow area and mild operation conditions. Membrane properties are the key part in terms of determining the separation efficiency in the OSN system. In this review paper, the recently reported OSN thin-film composite (TFC) membranes were investigated to understand insight of membrane materials and performance. Especially, we highlighted the representative study concepts and materials of the selective layer of OSN TFC membranes for non-polar solvents. The proper choice of monomers and additives for the selective layer forms much more interconnected voids and the enhanced microporosity, which can improve membrane performance of the OSN TFC membrane with reducing the transport resistance. Therefore, this review paper could be an important bridge to connect with the next-generation OSN TFC membranes for non-polar solvents.
The Roles of MicroRNAs in Male Infertility

MicroRNAs applications were vastly studied throughout the years, spanning from potential cancer biomarkers to targeted therapies for various diseases. Out of these utilizations, this paper focuses on their role in male infertility. Approximately 10–15% of worldwide couples are affected by infertility. Out of these, 50% are due to male determinants. The majority of cases still have an undetermined cause. Previous studies have found that the aberrant expression of microRNAs could be linked to certain reproductive dysfunctions in males. Further on, this study looked into the most recent literature published on this subject in order to assess the connection between the up-/down-regulation of various microRNAs and the roles they play in male infertility. MicroRNAs were found to be abundant and stable in the seminal liquid, which led to a facile identification using regular RNA detection methods. It was observed that the concentration of microRNAs in semen was modified in the case of patients suffering from asthenozoospermia and azoospermia. Moreover, idiopathic male infertility was associated with a single nucleotide polymorphism of the microRNA binding site. Future studies should focus their attention on discovering future treatments against male infertility targeting specific microRNAs and also on developing new and improved contraceptive methods.
Enhanced Skin Permeation of Estradiol by Dimethyl Sulfoxide Containing Transdermal Patches

Dimethyl sulfoxide is a well-known and widely used dermal penetration enhancer. Its incorporation in transdermal patches would be highly desirable; however, due to its volatility this is extremely challenging. Here, we report on the feasibility of a dimethyl sulfoxide (DMSO) containing transdermal system containing estradiol as a model compound. Transdermal patches were prepared from duro-tak® 387-2510 containing various DMSO concentrations at different drying temperatures. The resulting patches were analyzed for DMSO content, estradiol and DMSO release, estradiol and DMSO permeation through excised porcine skin, and recrystallization during stability testing. Drying conditions in the range of 35° to 40° allowed a complete polymer solvents removal while retaining significant amounts of DMSO (≤10 mg/patch). Estradiol skin permeation increased 4-fold (Jss = 4.12 µg/cm−2·h−1) compared to DMSO-negative control (Jss = 1.1 ± 0.2 µg/cm−2·h−1). As additional benefit, estradiol recrystallization was inhibited by DMSO at even lowest solvent concentrations. Storage stability was limited to 6 months at 25 °C with a surprising discrepancy between DMSO content (significantly lower) and flux (not significantly different). Although the technical feasibility range is relatively narrow, such DMSO-containing matrix-type patches are able to significantly enhance drug permeation through the skin while ameliorating the product stability against recrystallization.
JNK and p38 Inhibitors Prevent Transforming Growth Factor-β1-Induced Myofibroblast Transdifferentiation in Human Graves’ Orbital Fibroblasts

Transforming growth factor-β1 (TGF-β1)-induced myofibroblast transdifferentiation from orbital fibroblasts is known to dominate tissue remodeling and fibrosis in Graves’ ophthalmopathy (GO). However, the signaling pathways through which TGF-β1 activates Graves’ orbital fibroblasts remain unclear. This study investigated the role of the mitogen-activated protein kinase (MAPK) pathway in TGF-β1-induced myofibroblast transdifferentiation in human Graves’ orbital fibroblasts. The MAPK pathway was assessed by measuring the phosphorylation of p38, c-Jun N-terminal kinase (JNK), and extracellular-signal-regulated kinase (ERK) by Western blots. The expression of connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), and fibronectin representing fibrogenesis was estimated. The activities of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) responsible for extracellular matrix (ECM) metabolism were analyzed. Specific pharmacologic kinase inhibitors were used to confirm the involvement of the MAPK pathway. After treatment with TGF-β1, the phosphorylation levels of p38 and JNK, but not ERK, were increased. CTGF, α-SMA, and fibronectin, as well as TIMP-1 and TIMP-3, were upregulated, whereas the activities of MMP-2/-9 were inhibited. The effects of TGF-β1 on the expression of these factors were eliminated by p38 and JNK inhibitors. The results suggested that TGF-β1 could induce myofibroblast transdifferentiation in human Graves’ orbital fibroblasts through the p38 and JNK pathways.
The Role of Rigid Residues in Modulating TEM-1 β-Lactamase Function and Thermostability

The relationship between protein motions (i.e., dynamics) and enzymatic function has begun to be explored in β-lactamases as a way to advance our understanding of these proteins. In a recent study, we analyzed the dynamic profiles of TEM-1 (a ubiquitous class A β-lactamase) and several ancestrally reconstructed homologues. A chief finding of this work was that rigid residues that were allosterically coupled to the active site appeared to have profound effects on enzyme function, even when separated from the active site by many angstroms. In the present work, our aim was to further explore the implications of protein dynamics on β-lactamase function by altering the dynamic profile of TEM-1 using computational protein design methods. The Rosetta software suite was used to mutate amino acids surrounding either rigid residues that are highly coupled to the active site or to flexible residues with no apparent communication with the active site. Experimental characterization of ten designed proteins indicated that alteration of residues surrounding rigid, highly coupled residues, substantially affected both enzymatic activity and stability; in contrast, native-like activities and stabilities were maintained when flexible, uncoupled residues, were targeted. Our results provide additional insight into the structure-function relationship present in the TEM family of β-lactamases. Furthermore, the integration of computational protein design methods with analyses of protein dynamics represents a general approach that could be used to extend our understanding of the relationship between dynamics and function in other enzyme classes.
New-Onset Diabetes after Kidney Transplantation

New-onset diabetes mellitus after transplantation (NODAT) is a frequent complication in kidney allograft recipients. It may be caused by modifiable and non-modifiable factors. The non-modifiable factors are the same that may lead to the development of type 2 diabetes in the general population, whilst the modifiable factors include peri-operative stress, hepatitis C or cytomegalovirus infection, vitamin D deficiency, hypomagnesemia, and immunosuppressive medications such as glucocorticoids, calcineurin inhibitors (tacrolimus more than cyclosporine), and mTOR inhibitors. The most worrying complication of NODAT are major adverse cardiovascular events which represent a leading cause of morbidity and mortality in transplanted patients. However, NODAT may also result in progressive diabetic kidney disease and is frequently associated with microvascular complications, eventually determining blindness or amputation. Preventive measures for NODAT include a careful assessment of glucose tolerance before transplantation, loss of over-weight, lifestyle modification, reduced caloric intake, and physical exercise. Concomitant measures include aggressive control of systemic blood pressure and lipids levels to reduce the risk of cardiovascular events. Hypomagnesemia and low levels of vitamin D should be corrected. Immunosuppressive strategies limiting the use of diabetogenic drugs are encouraged. Many hypoglycemic drugs are available and may be used in combination with metformin in difficult cases. In patients requiring insulin treatment, the dose and type of insulin should be decided on an individual basis as insulin requirements depend on the patient’s diet, amount of exercise, and renal function.
Crack Detection and Localisation in Steel-Fibre-Reinforced Self-Compacting Concrete Using Triaxial Accelerometers

Cracking in concrete structures can significantly affect their structural integrity and eventually lead to catastrophic failure if undetected. Recent advances in sensor technology for structural health monitoring techniques have led to the development of new and improved sensors for real-time detection and monitoring of cracks in various applications, from laboratory tests to large structures. In this study, triaxial accelerometers have been employed to detect and locate micro- and macrocrack formation in plain self-compacting concrete (SCC) and steel-fibre-reinforced SCC (SFRSCC) beams under three-point bending. Experiments were carried out with triaxial accelerometers mounted on the surface of the beams. The experimental results revealed that triaxial accelerometers could be used to identify the locations of cracks and provide a greater quantity of useful data for more accurate measurement and interpretation. The study sheds light on the structural monitoring capability of triaxial acceleration measurements for SFRSCC structural elements that can act as an early warning system for structural failure.