MTA-SZTE Research Group on Artificial Intelligence

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    Antibiotic candidates for Gram-positive bacterial infections induce multidrug resistance

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    Several antibiotic candidates are in development against Gram-positive bacterial pathogens, but their long-term utility is unclear. To investigate this issue, we studied the laboratory evolution of resistance to antibiotics that have not yet reached the market. We found that, with the exception of compound SCH79797, antibiotic resistance generally readily evolves in Staphylococcus aureus . Cross-resistance was detected between such candidates and antibiotics currently in clinical use, including vancomycin, daptomycin, and the promising antibiotic candidate teixobactin. These patterns were driven by overlapping molecular mechanisms through mutations in regulatory systems. In particular, teixobactin-resistant bacteria displayed clinically relevant multidrug resistance and retained their virulence in an invertebrate infection model, raising concerns. More generally, we demonstrate that putative resistance mutations against candidate antibiotics are already present in natural bacterial populations. Therefore, antibiotic resistance in nature may evolve readily from the selection of preexisting genetic variants. Our work highlights the importance of predicting future evolution of resistance to antibiotic candidates at an early stage of drug development

    Bacteriophage Treatment Induces Phenotype Switching and Alters Antibiotic Resistance of ESBL Escherichia coli

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    Background/Objectives: Bacteriophage therapy represents a promising strategy to combat multidrug-resistant pathogens, such as Escherichia coli. In this study, we explored the effects of a bacteriophage infection on an Extended Spectrum Beta-Lactamase (ESBL) positive E. coli isolate. Methods: We used next generation sequencing, proteomics and phenotypic screens to investigate the effect of bacteriophage infections on E. coli metabolism and resistance phenotypes. Results: The bacteriophage infection led to notable alterations in colony morphology, indicating profound changes in bacterial metabolism. Proteomic analysis revealed significant shifts in protein expression, with 65 proteins upregulated and 246 downregulated post-infection. The downregulated proteins were involved in various metabolic pathways, including nucleic acid, protein and lipid metabolism, and iron acquisition. Bacteriophage treatment also led to increased bacterial membrane permeability. Altogether, these alterations in bacterial metabolism and membrane permeability may lead to a general reduction in antibiotic resistance. Indeed, the bacteriophage-infected E. coli exhibited increased sensitivity to various classes of antibiotics, including beta-lactams, fluoroquinolones, trimethoprim-sulfamethoxazole, and aminoglycosides. Conclusions: Our findings highlight the potential of bacteriophage therapy as an adjunct to existing antibiotics, enhancing their efficacy against resistant strains

    Comparative analysis of nickel–titanium instrumentation systems for root canal anatomy preservation: an in vitro study

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    This study aimed to evaluate the efficacy of various nickel–titanium (Ni-Ti) root canal instrumentation systems in preserving root canal anatomy, focusing on their capacity to limit changes in canal angulation. One hundred canals in fifty extracted human molars were prepared with different techniques: Step-Back, Reciproc, MTwo, ProTaper Universal (PTU), and ProTaper Next (PTN). The curvature of each canal was measured before and after treatment using Schneider’s methodology, a widely accepted method for assessing canal curvature. Descriptive and statistical analyses, including the Kruskal–Wallis test, were employed to compare angular changes across the systems. The results indicated that all techniques effectively reduced canal curvature, with each system exhibiting a reduction in mean canal angle after instrumentation. Although the Reciproc system showed the smallest mean change in angulation, no statistically significant differences were identified between any of the systems (p = 0.182). This finding suggests that while minor differences in performance may exist, they do not translate into clinically meaningful distinctions in preserving root canal anatomy. The Reciproc system’s slight advantage aligns with other studies, highlighting its conservative design and minimal dentinal stress; however, its superiority was not statistically validated in this study. The results suggest that all five systems are clinically comparable in preserving root canal anatomy, highlighting that dentists can choose from these widely available techniques without compromising anatomical preservation. While this study had limitations, including a relatively small sample size and an in vitro design, it aligns with previous findings on the mechanical behavior of Ni-Ti systems in endodontic practice

    Gibberellic Acid (GA3): a Versatile Chiral Building Block for Syntheses of Pharmaceutical Agents

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    Gibberellic acid (GA3), an ent‐kaurene tetracyclic diterpene, has been considered to be a chiral pool for the chemical transformation of significant heterocyclic compounds. This chiral pool continues to influence modern synthetic chemistry as an inexpensive and versatile starting material since it is widely applied in agriculture. This review focuses on the stereoselective syntheses of bioactive agents with pharmaceutical potency prepared from Gibberellic acid

    Thrombolysis in lacunar stroke: Comparison of early neurological improvement and 90-day functional outcome with cardioembolic stroke without large-vessel occlusion

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    Thrombolysis (IVT) is effective in the treatment of lacunar stroke (LAC). However, most studies compared the outcome of LAC to a heterogenous control group. We aimed to compare early neurological improvement (ENI) and late functional outcomes following thrombolysis for LAC with a homogenous control group of cardioembolic stroke (CE) without large-vessel occlusion (LVO).Patient data were obtained from the national multicentre STAY ALIVE Acute Stroke Registry. At each centre, a team of vascular neurologists determined the TOAST classification. ENI was defined as a minimum 4-point decrease in the NIHSS score between admission and discharge, or a complete resolution of symptoms. For late functional outcome, we analysed the dichotomised 90-day mRS scores (good outcome was mRS≤2).142 LAC and 156 CE patients were analysed. Following IVT, the percentage of ENI did not differ significantly (LAC 41.1% vs CE 49.7%, p=0.154), and multivariable analysis did not identify any clinical parameters that would predict ENI after IVT in either group. LAC patients had unfavourable, albeit non-significant, odds of having good 90-day functional outcomes compared to CE patients (aOR 0.483, 95%CI 0.201-1.161, p=104).We report the first analysis of short- and long-term outcomes of IVT in LAC, using a homogenous control group of CE patients without LVO. The prevalence of ENI and 90-day functional outcomes were similar. However, LAC patients had unfavourable odds of achieving good functional outcomes compared to the control group. Therefore, we emphasise that LAC should not be considered a minor stroke subtype

    From Thought to Action: The Decision‐Making Process of Foster Parents

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    Although foster care represents an essential practice for helping children and families in difficult situations, nowadays, in Italy, the number of people open to engaging in this kind of care is limited compared to the real need, and agencies have difficulties recruiting new foster parents. The present qualitative study is aimed at identifying the process that leads families to become foster parents and investigating how this decision has been put into practice, with the aim of improving practices in the foster care system. A constructivist grounded theory approach was used to study the experiences of foster parent dyads in Northern Italy. The basic social process of ‘acting generatively’ was identified. This represented the inner need to act experienced by the people who approach foster care and who are guided by the desire to go beyond the self, to serve others and to take care of future generations. Six axial codes representing the six main phases in this process, characterized from a sociorelational point of view, were identified: values awareness, generative ideation, generative agreement, evaluation, generative intention and generative action. This article describes a foster decision‐making model that may help social workers in recruiting foster families

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