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Topology Induced by Fuzzy Coloring in Fuzzy Graphs
No full textIn fuzzy graphs, the concept of fuzzy topology induced by fuzzy coloring on the vertex set of a fuzzy graph is a relatively advanced and specialized topic that combines the principles of fuzziness, graph theory, and topology. Fuzzy topology typically refers to the study of topological structures where the open sets are not crisp but fuzzy in nature, meaning they have degrees of membership rather than being either fully included or excluded. When fuzzy coloring is applied to set of vertices of a fuzzy graph, it leads to the creation of fuzzy topological spaces where the relationships between the vertices are characterized by fuzzy sets or fuzzy relations. This interplay between fuzzy coloring and fuzzy topology can help model systems with imprecise, uncertain, or gradated connectivity. This chapter provides the technique of inducing fuzzy topology on fuzzy graph’s set of vertices induced by vertex coloring. It initiates color lower fuzzy approximation and color upper fuzzy approximation of fuzzy subgraphs and defines the closed and open sets of the fuzzy topology generated by fuzzy chromatic
partition. It explores key properties of color lower fuzzy approximation and color upper fuzzy approximation of fuzzy subgraphs. It also establishes some real-time applications of the color lower fuzzy approximation and color upper fuzzy approximation
Remibrutinib in Chronic Spontaneous Urticaria
No full textBackground: Chronic spontaneous urticaria is an idiopathic syndrome defined by recurring itch, hives, or angioedema (or a combination of these symptoms) for more than 6 weeks. Remibrutinib, an oral, highly selective Bruton's tyrosine kinase inhibitor, showed efficacy and favorable safety in phase 2b trials. Data from phase 3 trials are needed. Methods: In the identical, multicenter, double-blind, randomized, placebo-controlled REMIX-1 and REMIX-2 trials, we evaluated the efficacy and safety of remibrutinib in patients with symptomatic chronic spontaneous urticaria after treatment with second-generation H1-antihistamines. Patients were randomly assigned in a 2:1 ratio to receive oral remibrutinib at a dose of 25 mg twice daily or placebo. The primary end point was the change from baseline to week 12 in the urticaria activity score during a 7-day period (UAS7), which comprises severity scores for itch and hives during 1 week (scores range from 0 to 42, with higher scores indicating greater severity). Key secondary end points included adverse events and a UAS7 of 6 or lower at weeks 2 and 12 and a UAS7 of 0 at week 12. Results: A total of 470 patients in REMIX-1 and 455 in REMIX-2 were randomly assigned to receive either remibrutinib (313 and 300 patients, respectively) or placebo (157 and 155 patients, respectively). The remibrutinib group had a significantly greater decrease in the UAS7 at week 12 than the placebo group (least-squares mean [±SE] change, -20.0±0.7 vs. -13.8±1.0 [P<0.001] in REMIX-1 and -19.4±0.7 vs. -11.7±0.9 [P<0.001] in REMIX-2), which appeared to be sustained through week 24. At week 12, significantly more patients in the remibrutinib group than in the placebo group had a UAS7 of 6 or lower (REMIX-1, 49.8% vs. 24.8% [P<0.001]; REMIX-2, 46.8% vs. 19.6% [P<0.001]) and a UAS7 of 0 (REMIX-1, 31.1% vs. 10.5% [P<0.001]; REMIX-2, 27.9% vs. 6.5% [P<0.001]). The percentages of patients with any adverse event and with serious adverse events were similar in the remibrutinib group and the placebo group, although a higher percentage of patients in the remibrutinib group than in the placebo group had petechiae (3.8% vs. 0.3% in the combined groups). Conclusions: Treatment with oral remibrutinib resulted in a significant improvement in a composite measure of itching and hives at week 12. (Funded by Novartis Pharmaceuticals; REMIX-1 and REMIX-2 ClinicalTrials.gov numbers, NCT05030311 and NCT05032157, respectively.)
Skyrmions in Nanotechnology
No full textSkyrmions, topologically protected textures, have been observed in different fields of nanotechnology and have emerged as promising candidates for different applications due to their topological stability, low-power operation, and dynamic response to external stimuli. First introduced in particle physics, skyrmions have since been observed in different condensed matter fields, including magnetism, ferroelectricity, photonics, and acoustics. Their unique topological properties enable robust manipulation and detection, paving the way for innovative applications in room temperature sensing, storage, and computing. Recent advances in materials engineering and device integration have demonstrated several strategies for an efficient manipulation of skyrmions, addressing key challenges in their practical implementation. In this review, we summarize the state-of-the-art research on skyrmions across different platforms, highlighting their fundamental properties and characteristics, recent experimental breakthroughs, and technological potential. We present future perspectives and remaining challenges, emphasizing the interdisciplinary impact of skyrmions on nanotechnology
Transcranial magnetic resonance imaging–guided focused ultrasound for neuropathic pain treatment
No full textIntroduction: Magnetic resonance imaging-guided focused ultrasound (MRgFUS) has shown promising results for a variety of neurological conditions, including movement disorders, brain tumors, and degenerative diseases. Recent clinical trials have demonstrated that MRgFUS can produce therapeutic effects in essential tremor (ET) and Parkinson’s disease (PD), comparable to those achieved with other neurosurgical interventions. Furthermore, there has been increasing attention on the development of FUS technology and its clinical applications, aimed at exploring new uses and enhancing existing ones. Areas covered: In this review, a comprehensive search was conducted across multiple platforms, including PubMed, Scopus, and the Cochrane Library. Filters were applied to include studies based on publication year and clinical trials involving human subjects (excluding animal studies). A thorough analysis of the results was crucial for achieving the objectives of our research. While some studies are still awaiting results, they show promise; others have already been completed. Expert opinion: The authors specifically selected six studies that yielded excellent results, covering aspects such as treatment side effects, pain location, key findings, ultrasound temperature, and sample size. he aim of this review is to provide an overview of the recent literature and ongoing clinical trials regarding the application of MRgFUS in the treatment of neuropathic pain
Measurement of the muon flux in the tunnels of Doss Trento hill
No full textIn the context of astroparticle physics, nuclear astrophysics and quantum computing projects, it is important identifying underground laboratories where the cosmogenic background is suppressed. Located about 500 m far from the center of Trento (Italy) the Piedicastello tunnels are covered by 100 m limestone rock of the Doss Trento hill. The site exceeds 6000m2 surface and is currently hosting events, temporary exhibitions, and educational activities. The cosmogenic background was measured in different locations within the Piedicastello tunnels with three portable scintillator telescopes having different geometrical acceptances. The muon flux measured in the deepest part was found to be about two orders of magnitude lower than the surface flux. This preliminary measurement suggests the use of the site as a facility in which a low environmental background is required
Raffaello Franchini e Girolamo Cotroneo interpreti del rapporto Croce-Dilthey
No full textL'articolo si propone di mettere in evidenza le analisi del difficile rapporto di Benedetto Croce con lo storicismo Diltheyano operate da due pensatori contemporanei - Raffaello Franchini e Girolamo Cotroneo - dalla comune matrice crocian
The SIRT2-p53 axis is involved in the antileukemic effect of bergamot juice extract and flavanones in an in vitro model of M5-subtype acute myeloid leukemia
No full textAcute myeloid leukemia (AML) is one of the most alarming hematological malignancies, being frequently associated with the lowest survival rate compared to other types of leukemia. AML arises and progresses with the acquisition of new genetic and/or epigenetic modifications, responsible for its high genetic and clinical heterogeneity. Gene aberrations, such as the over-expression of SIRT2, an enzyme belonging to the histone deacetylases family, represent a key mechanism of AML pathogenesis. The SIRT2 upregulation was associated with proliferation and survival of AML cells and is particularly evident in AML patients belonging to the M5 subtype. Therefore, novel effective approaches and molecular targets are constantly researched to improve the life expentancy of AML patients. An ever-growing interest towards plant kingdom by the scientific community brought to light several bioactive molecules, including flavonoids, which stood out among others as potential anticancer agents. One of the most studied sources of this class of phytochemicals is Citrus fruits, whose species are widespread throughout the world. In particular, Citrus bergamia Risso (bergamot) has attracted the interest of the scientific community for its pharmacological properties, among which the anticancer properties demonstrated in a wide array of solid tumors, but not yet in the field of hematological malignancies, such as AML.
Therefore, for the first time, we aimed at the investigation of the potential antileukemic activity of a flavonoid-rich extract of bergamot juice (BJe), along with the most common flavonones of the whole Citrus genus (i.e., naringenin – NAR, hesperetin -HSP, naringin – NRG, neohesperidin - NHP) in human leukemia THP-1 cell line, employed as in vitro model of AML-M5. Subsequently, acknowledged the SIRT2 crucial role in AML-M5 progression, we evaluated the potential inhibition of SIRT2 enzyme as an antileukemic mechanism, through in silico, cell-free and in vitro models.
Our results demonstrated that BJe, NAR and HSP induced a significant reduction of THP-1 cell proliferation, without altering the growth of non-cancer peripheral blood mononuclear cells (PBMCs). The antiproliferative effects of BJe and the investigated flavanones were related to a cell cycle arrest in S phase and an induction of apoptosis. Both mechanisms were contextually confirmed at molecular level, where both BJe, NAR and HSP modulated the gene and protein expressions of S phase regulators, such as p21 and cyclin E1, as well as of apoptotic effectors, such as caspase 3.
Interestingly, one of mechanisms responsible for the antiproliferative effects induced by BJe/NAR/HSP in leukemia THP-1 cells might also have been the inhibition of SIRT2 enzyme. This is because NAR and HSP were able to directly interact with the SIRT2 inhibitory site, as detected from molecular docking simulations. Moreover, both BJe, NAR and HSP, as well even more their equimolar combination (NAR-HSP) reduced the SIRT2 activity in the isolated enzyme (cell-free model). A SIRT2 inhibition by BJe, NAR, HSP and by their synergistic combination (NAR-HSP) was witnessed also in THP-1 cells, through an increase of acetylated p53, a specific substrate for SIRT2 deacetylation. Both BJe, NAR, and HSP were also able to reduce SIRT2 gene expression, yet only BJe significantly enhanced the gene and protein levels of the downstream factor p53.
Our results suggested the role of BJe, NAR and HSP as potential antileukemic agents by targeting the SIRT2/p53 axis, which seems to be implied in both cell cycle arrest and apoptosis, induced in leukemia THP-1 cells. Therefore, BJe as well as the Citrus flavanones NAR and HSP were unveiled to be promising candidates in the AML-M5 managment by acting as SIRT2 inhibitors
Bioccumulation and biochemical response of cadmium in Labeo rohita accross varying sizes
No full textThis study assessed the effects of sublethal Cd exposure (0.66 mg·L−1) on Labeo rohita (n = 270) of different size groups over 1, 7, and 14 days. Results revealed that Cd accumulation in gill, intestine, and kidney increased significantly, with the highest levels in smaller fish. Antioxidant enzymes (CAT, SOD) and GST activity declined, particularly on day 14. Treated groups showed elevated liver/plasma protein, glucose, and cortisol levels, indicating oxidative stress and disrupted biochemical homeostasis. Smaller fish were more affected. These findings highlight Cd toxicity's implications for aquatic ecosystems and human health, emphasizing the need for environmental monitoring and pollution control
Tipizzazioni grafiche e scribi greci a Ossirinco tra I e III sec. d.C. Nuove (e vecchie) identificazioni
No full textWilliam A. Johnson’s seminal book (Bookrolls and Scribes in Oxyrhynchus, Toronto 2004) oπers a comprehensive bibliological discussion of the literary volumina produced at Oxyrhynchus. In this work, Johnson lists 45 Greek scribes, though some of these identifications remain uncertain. Later research have led to identify additional copyists active in other volumina, as well as newly discovered papyrus fragments that can be traced back to already known scribes. Several hands can be categorized into well-defined graphic types or ‘normative scripts’, despite displaying idiosyncratic features that allow them to be identified and distinguished from other similar hands. The present contribution has a twofold goal: i) to analyse some graphic typologies attested at Oxyrhynchus by several hands: some of these scribes have already been detected, while others are recognized here for the first time; 2) to address some methodological
challenges on the dfficult identification of new copyists when dealing with distinct graphic types
and a very fragmentary evidence, as is the case of our papyrus pieces. Frequently, we are lacking
of a suffcient amount of text to make wide-ranging graphic comparisons