Miracle-dz/UniFAR-FTUs huggingface dataset:
Chronic Inflammatory Status Observed in Patients with Type 2 Diabetes Induces Modulation of Cytochrome P450 Expression and Activity

Diabetes mellitus is a metabolic disease that causes a hyperglycemic status which leads, over time, to serious damage to the heart, blood vessels, eyes, kidneys and nerves. The most frequent form of diabetes is type 2 diabetes mellitus (T2DM) which is often part of a metabolic syndrome (hyperglycaemia, hypertension, hypercholesterolemia, abdominal obesity) that usually requires the use of several medications from different drug classes to bring each of these conditions under control. T2DM is associated with an increase in inflammatory markers such as interleukin-6 (IL-6) and the tumor necrosis factor alpha (TNF-α). Higher levels of IL-6 and TNF-α are associated with a downregulation of several drug metabolizing enzymes, especially the cytochrome P450 (P450) isoforms CYP3As and CYP2C19. A decrease in these P450 isoenzymes may lead to unexpected rise in plasma levels of substrates of these enzymes. It could also give rise to a mismatch between the genotypes determined for these enzymes, the predicted phenotypes based on these genotypes and the phenotypes observed clinically. This phenomenon is described as phenoconversion. Phenoconversion typically results from either a disease (such as T2DM) or concomitant administration of medications inducing or inhibiting (including competitive or non-competitive inhibition) a P450 isoenzyme used by other substrates for their elimination. Phenoconversion could have a significant impact on drug effects and genotypic-focused clinical outcomes. As the aging population is exposed to polypharmacy along with inflammatory comorbidities, consideration of phenoconversion related to drug metabolizing enzymes is of importance when applying pharmacogenomic results and establishing personalized and more precise drug regimens.
Radiation-Induced Senescence Reprograms Secretory and Metabolic Pathways in Colon Cancer HCT-116 Cells

Understanding the global metabolic changes during the senescence of tumor cells can have implications for developing effective anti-cancer treatment strategies. Ionizing radiation (IR) was used to induce senescence in a human colon cancer cell line HCT-116 to examine secretome and metabolome profiles. Control proliferating and senescent cancer cells (SCC) exhibited distinct morphological differences and expression of senescent markers. Enhanced secretion of pro-inflammatory chemokines and IL-1, anti-inflammatory IL-27, and TGF-β1 was observed in SCC. Significantly reduced levels of VEGF-A indicated anti-angiogenic activities of SCC. Elevated levels of tissue inhibitors of matrix metalloproteinases from SCC support the maintenance of the extracellular matrix. Adenylate and guanylate energy charge levels and redox components NAD and NADP and glutathione were maintained at near optimal levels indicating the viability of SCC. Significant accumulation of pyruvate, lactate, and suppression of the TCA cycle in SCC indicated aerobic glycolysis as the predominant energy source for SCC. Levels of several key amino acids decreased significantly, suggesting augmented utilization for protein synthesis and for use as intermediates for energy metabolism in SCC. These observations may provide a better understanding of cellular senescence basic mechanisms in tumor tissues and provide opportunities to improve cancer treatment.
Effects of Focal Knee Joint Cooling on Static and Dynamic Strength of the Quadriceps: Innovative Approach to Muscle Conditioning

Recent evidence suggests an innovative approach to muscle conditioning: focal knee joint cooling (FKJC) appears to improve quadriceps function, including static (isometric) strength. However, there is limited evidence on the effects of FKJC on dynamic (concentric and eccentric) strength. Thus, the purpose of the study was to examine dynamic quadriceps strength following FKJC as well as static strength. Twenty-one college-aged participants volunteered. They randomly underwent 20 min of FKJC and control condition at least 72 h apart. FKJC involves two ice bags, placed on the anterior and posterior surfaces of the knee, whereas the control condition received a plastic ice bag filled with candy corn. We assessed isometric and isokinetic (concentric and eccentric) quadriceps strength at two different velocities (60°/s and 180°/s). Participants performed three maximal voluntary contractions for each mode of muscle contraction, before and after each treatment (immediately, 20, and 40 min after). The outcome variable was maximum knee extension peak torque. FKJC did not change peak torque during any mode of muscle contraction (p > 0.05). The current findings suggest that 20 min of FKJC does not change static (isometric) or dynamic (isokinetic) strength of the quadriceps. FKJC was neither beneficial nor harmful to static or dynamic muscular strength.
Glucose Prediction under Variable-Length Time-Stamped Daily Events: A Seasonal Stochastic Local Modeling Framework

Accurate glucose prediction along a long-enough time horizon is a key component for technology to improve type 1 diabetes treatment. Subjects with diabetes might benefit from supervision and control systems that accurately predict risks and trigger corrective actions early enough with improved mitigation. However, large intra-patient variability poses big challenges to glucose prediction. In previous works by the authors, clustering and local modeling techniques with seasonal stochastic models proved to be efficient, allowing for good glucose prediction accuracy for long prediction horizons. Continuous glucose monitoring (CGM) data were partitioned into fixed-length postprandial time subseries and clustered with Fuzzy C-Means to collect similar behaviors, enforcing seasonality at each cluster after subseries concatenation. Then, seasonal stochastic models were identified for each cluster and local predictions were integrated into a global prediction. However, free-living conditions do not support the fixed-length partition of CGM data since daily events duration is variable. In this work, a new algorithm is provided to overcome this constraint, allowing better coping with patient’s variability under variable-length time-stamped daily events in supervision and control applications. Besides predicted glucose, two real-time indices are additionally provided—a crispness index, indicating good representation of current glucose behavior by a single model, and a normality index, allowing for the detection of an abnormal glucose behavior (unusual according to registered historical data). The framework is tested in a proof-of-concept in silico study with ten patients over four month training data and two independent two month validation datasets, with and without abnormal behaviors, from the distribution version of the UVA/Padova simulator extended with diverse sources of intra-patient variability.
Phytochemicals Targeting JAK–STAT Pathways in Inflammatory Bowel Disease: Insights from Animal Models

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract that consists of Crohn’s disease (CD) and ulcerative colitis (UC). Cytokines are thought to be key mediators of inflammation-mediated pathological processes of IBD. These cytokines play a crucial role through the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) signaling pathways. Several small molecules inhibiting JAK have been used in clinical trials, and one of them has been approved for IBD treatment. Many anti-inflammatory phytochemicals have been shown to have potential as new drugs for IBD treatment. This review describes the significance of the JAK–STAT pathway as a current therapeutic target for IBD and discusses the recent findings that phytochemicals can ameliorate disease symptoms by affecting the JAK–STAT pathway in vivo in IBD disease models. Thus, we suggest that phytochemicals modulating JAK–STAT pathways are potential candidates for developing new therapeutic drugs, alternative medicines, and nutraceutical agents for the treatment of IBD.
Pinosylvin Shifts Macrophage Polarization to Support Resolution of Inflammation

Pinosylvin is a natural stilbenoid found particularly in Scots pine. Stilbenoids are a group of phenolic compounds identified as protective agents against pathogens for many plants. Stilbenoids also possess health-promoting properties in humans; for instance, they are anti-inflammatory through their suppressing action on proinflammatory M1-type macrophage activation. Macrophages respond to environmental changes by polarizing towards proinflammatory M1 phenotype in infection and inflammatory diseases, or towards anti-inflammatory M2 phenotype, mediating resolution of inflammation and repair. In the present study, we investigated the effects of pinosylvin on M2-type macrophage activation, aiming to test the hypothesis that pinosylvin could polarize macrophages from M1 to M2 phenotype to support resolution of inflammation. We used lipopolysaccharide (LPS) to induce M1 phenotype and interleukin-4 (IL-4) to induce M2 phenotype in J774 murine and U937 human macrophages, and we measured expression of M1 and M2-markers. Interestingly, along with inhibiting the expression of M1-type markers, pinosylvin had an enhancing effect on the M2-type activation, shown as an increased expression of arginase-1 (Arg-1) and mannose receptor C type 1 (MRC1) in murine macrophages, and C-C motif chemokine ligands 17 and 26 (CCL17 and CCL26) in human macrophages. In IL-4-treated macrophages, pinosylvin enhanced PPAR-γ expression but had no effect on STAT6 phosphorylation. The results show, for the first time, that pinosylvin shifts macrophage polarization from the pro-inflammatory M1 phenotype towards M2 phenotype, supporting resolution of inflammation and repair.
New O3-Type Layer-Structured Na0.80[Fe0.40Co0.40Ti0.20]O2 Cathode Material for Rechargeable Sodium-Ion Batteries

Herein, we formulated a new O3-type layered Na0.80[Fe0.40Co0. 40Ti0.20]O2 (NFCTO) cathode material for sodium-ion batteries (SIBs) using a double-substitution concept of Co in the parent NaFe0.5Co0. 5O2, having the general formula Na1-x[Fe0.5–x/2Co0.5–x/2M4+x]O2 (M4+ = tetravalent ions). The NFCTO electrode delivers a first discharge capacity of 108 mAhg−1 with 80% discharge capacity retention after 50 cycles. Notably, the first charge–discharge profile shows asymmetric yet reversible redox reactions. Such asymmetric redox reactions and electrochemical properties of the NFCTO electrode were correlated with the phase transition behavior and charge compensation reaction using synchrotron-based in situ XRD and ex situ X-ray absorption spectroscopy. This study provides an exciting opportunity to explore the interplay between the rich chemistry of Na1–x[Fe0.5–x/2Co0.5–x/2M4+x]O2 and sodium storage properties, which may lead to the development of new cathode materials for SIBs.
Distribution and Polarization of Caries in Adolescent Populations

The aim of this study was to determine the proportion of adolescents with severe caries to analyze the prevalence of caries and to visualize the unequal distribution. Data from three epidemiological studies (10- and 15-year-olds: GINIplus and LISA cohorts in Munich, Bavaria; 12-year-olds: LAGZ survey in Bavaria, Germany) with 2875 adolescents were available for analysis. All individuals were examined according to the WHO standard. Statistics included the calculation of mean dmft/DMFT values (standard deviation), Significant Caries Index (SiC) values, Specific Affected Caries Index (SaC) values, and Lorenz curves. Overall caries-free status was 58.6% in primary and 83.9% in secondary teeth (10-year-olds), 61.5% (12-year-olds), and 64.6% (15-year-olds). The proportion of 12- and 15-year-olds with at least four DMFTs was 9.4% and 8.3%, respectively. In addition, eight 15-year-olds with DMFT values ≥8 (0.6%) were registered. The SaC/SiC values amounted to 1.8/0.9 DMFT (10-year-olds), 2.6/2.8 DMFT (12-year-olds), and 2.5/2.5 DMFT (15-year-olds). The mean DMFT values in the upper 1% of subjects were 4.2 DMFT (10-year-olds), 8.5 DMFT (12-year-olds), and 8.5 DMFT (15-year-olds). Thus, caries is not equally distributed throughout adolescence, but individuals with severe caries are rare. Nevertheless, further interdisciplinary research seems to be needed to clarify potential risk factors.
Combined Effect of Impregnation with an Origanum vulgare Infusion and Osmotic Treatment on the Shelf Life and Quality of Chilled Chicken Fillets

The scope of this work is the study of a combined process including a dipping step into an oregano (Origanum vulgare ssp. hirtum) infusion (OV) followed by osmotic treatment of chicken fillets at 15 °C. Chicken fillets were immersed in an osmotic solution consisting of 40% glycerol and 5% NaCl with (OV/OD) and without (OD) prior antioxidant enrichment in a hypotonic oregano solution. A comparative shelf life study of all the samples (untreated, OD and OV/OD treated) was then conducted at 4 °C in order to assess the impact of this process on the quality and shelf life of chilled chicken fillets. Microbial growth, lipid oxidation and color/texture changes were measured throughout the chilled storage period. Rates of microbial growth of pretreated fillets were significantly reduced, mainly as a result of water activity decrease (OD step). Rancidity development closely related to off odors and sensory rejection was greatly inhibited in treated fillets owing to both inhibitory factors (OD and OV), with water-soluble phenols (OV step) exhibiting the main antioxidant effect. Shelf life of treated chicken fillets exhibited a more than three-fold increase as compared to the untreated samples based on both chemical and microbial spoilage indices, maintaining a positive and pleasant sensory profile throughout the storage period examined.
Confocal Laser Microscopy in Neurosurgery: State of the Art of Actual Clinical Applications

Achievement of complete resections is of utmost importance in brain tumor surgery, due to the established correlation among extent of resection and postoperative survival. Various tools have recently been included in current clinical practice aiming to more complete resections, such as neuronavigation and fluorescent-aided techniques, histopathological analysis still remains the gold-standard for diagnosis, with frozen section as the most used, rapid and precise intraoperative histopathological method that permits an intraoperative differential diagnosis. Unfortunately, due to the various limitations linked to this technique, it is still unsatisfactorily for obtaining real-time intraoperative diagnosis. Confocal laser technology has been recently suggested as a promising method to obtain near real-time intraoperative histological data in neurosurgery, due to its established use in other non-neurosurgical fields. Still far to be widely implemented in current neurosurgical clinical practice, this technology was initially studied in preclinical experiences confirming its utility in identifying brain tumors, microvasculature and tumor margins. Hence, ex vivo and in vivo clinical studies evaluated the possibility with this technology of identifying and classifying brain neoplasms, discerning between normal and pathologic tissue, showing very promising results. This systematic review has the main objective of presenting a state-of-the-art summary on actual clinical applications of confocal laser imaging in neurosurgical practice.
Home and Neighborhood Physical Activity Location Availability among African American Adolescent Girls Living in Low-Income, Urban Communities: Associations with Objectively Measured Physical Activity

Based on the ecological model of active living, the neighborhood environment may relate to individual physical activity (PA) behaviors. The purposes of this study were to (1) generate a replicable neighborhood-level physical activity location availability score (PALAS) from data variables associated with physical activity among adolescents and adults, and apply this score to Baltimore City, Maryland, and (2) determine if relationships exist between PA and PA location availability. Geographic information systems (GISs) were used to create the PALAS. Using linear regression models, we examined relations between objectively measured PA among low-income, urban, predominantly African American adolescent girls (n = 555, 2009–2012 data collection), and the PALAS rating of their neighborhood environment (neighborhood PALAS) and their home neighborhood area (PALAS variables/subcomponents within 0.25 miles of the home). A PALAS map of the study area was created, illustrating neighborhoods varying in availability and variety of PA locations. After adjusting for confounders, a higher neighborhood PALAS (β = 0.10, p = 0.041) and the presence of a recreation center in the home neighborhood area (β = 0.46, p = 0.011) were associated with more minutes per day spent in moderate to vigorous PA. Policy makers and stakeholders should consider increasing access to PA locations as a strategy to promote PA among adolescent girls.
Equivalent Impedance Models for Electrochemical Nanosensor-Based Integrated System Design

Models of electrochemical sensors play a critical role for electronic engineers in designing electrochemical nanosensor-based integrated systems and are also widely used in analyzing chemical reactions to model the current, electrical potential, and impedance occurring at the surface of an electrode. However, the use of jargon and the different perspectives of scientists and electronic engineers often result in different viewpoints on principles of electrochemical models, which can impede the effective development of sensor technology. This paper is aimed to fill the knowledge gap between electronic engineers and scientists by providing a review and an analysis of electrochemical models. First, a brief review of the electrochemical sensor mechanism from a scientist’s perspective is presented. Then a general model, which reflects a more realistic situation of nanosensors is proposed from an electronic engineer point of view and a comparison between the Randles Model is given with its application in electrochemical impedance spectroscopy and general sensor design. Finally, with the help of the proposed equivalent model, a cohesive explanation of the scan rate of cyclic voltammetry is discussed. The information of this paper can contribute to enriching the knowledge of electrochemical sensor models for scientists and is also able to guide the electronic engineer on designing next-generation sensor layouts.
Recent Trends in Enzyme Immobilization—Concepts for Expanding the Biocatalysis Toolbox

Enzymes have been exploited by humans for thousands of years in brewing and baking, but it is only recently that biocatalysis has become a mainstream technology for synthesis. Today, enzymes are used extensively in the manufacturing of pharmaceuticals, food, fine chemicals, flavors, fragrances and other products. Enzyme immobilization technology has also developed in parallel as a means of increasing enzyme performance and reducing process costs. The aim of this review is to present and discuss some of the more recent promising technical developments in enzyme immobilization, including the supports used, methods of fabrication, and their application in synthesis. The review highlights new support technologies such as the use of well-established polysaccharides in novel ways, the use of magnetic particles, DNA, renewable materials and hybrid organic–inorganic supports. The review also addresses how immobilization is being integrated into developing biocatalytic technology, for example in flow biocatalysis, the use of 3D printing and multi-enzymatic cascade reactions.
Fiber Bragg Grating Pressure Sensor Integrated with Epoxy Diaphragm

A fiber Bragg grating (FBG) sensor integrated with an epoxy diaphragm was developed for the measurement of pressure and water level. The bending strain of a circular diaphragm induced by uniform pressure was transferred to the FBG sensor. The response of the FBG sensor to the pressure was observed in terms of the Bragg wavelength shift which is linearly proportional to the strain. The effect of epoxy diaphragm thickness on the sensitivity and accuracy was investigated. The experimental results show that the sensitivity of FBG/epoxy diaphragm pressure sensor is decreasing with the increase of the diaphragm thickness. The sensitivities of the FBG pressure sensors with diaphragm thicknesses of 0.5 mm, 0.7 mm, and 1.0 mm were 175.5 pm/kPa, 89.5 pm/kPa, and 43.7 pm/kPa, respectively. The pressure measured by the proposed FBG sensor was compared with theoretical prediction and a close agreement was observed.
Cannabinoids, Phenolics, Terpenes and Alkaloids of Cannabis

Cannabis sativa is one of the oldest medicinal plants in the world. It was introduced into western medicine during the early 19th century. It contains a complex mixture of secondary metabolites, including cannabinoids and non-cannabinoid-type constituents. More than 500 compounds have been reported from C. sativa, of which 125 cannabinoids have been isolated and/or identified as cannabinoids. Cannabinoids are C21 terpeno-phenolic compounds specific to Cannabis. The non-cannabinoid constituents include: non-cannabinoid phenols, flavonoids, terpenes, alkaloids and others. This review discusses the chemistry of the cannabinoids and major non-cannabinoid constituents (terpenes, non-cannabinoid phenolics, and alkaloids) with special emphasis on their chemical structures, methods of isolation, and identification.
Melatonin as a Topical/Systemic Formulation for the Management of Periodontitis: A Systematic Review

Objectives: To qualitatively and quantitatively review the use of melatonin as a topical/systemic formulation for the management of periodontitis. Materials and methods: PubMed; Scopus; and Web of Science databases were searched using the MesH terms “melatonin” and “periodontitis”. Title and abstracts were screened to eliminate irrelevant and duplicate articles. The full text data of the screened articles were assessed using the selection criteria. Results: Of 176 identified articles (PubMed-66; Scopus-56; Web of Science-52; Cross-reference-2), only 12 studies qualified to be included in the systematic review. Four studies assessed the independent effect of 1% topical melatonin formulation while 8 articles assessed the adjunctive use of systemic melatonin formulation (1–10 mg) following scaling and root planing (SRP). All studies showed an improvement in periodontal parameters such as pocket depth, clinical attachment loss, periodontal disease index, community periodontal index, gingival bleeding scores, and prognostic marker levels in saliva and serum. A meta-analysis of data from 2 studies revealed that 1–2 mg (systemic) melatonin supplementation reduced pocket depth; although the difference was not statistically significant and hence cannot be interpreted or used for conclusive evidence. Risk of Bias Assessment tool (RoBANS) and Cochrane Collaboration RoB tool elicited a high risk of bias in the included studies. GRADE (recommendation assessment, development, and evaluation) inferred a weak recommendation for the use of melatonin in periodontitis management. Conclusions: Melatonin supplementation (topical and systemic) in periodontitis patients improved key periodontal parameters including pocket depth and clinical attachment loss. Clinical relevance: Melatonin could be a potential host modulatory agent for periodontitis management; although the data from the present review should be interpreted carefully due to the associated high risk of bias.