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Abstract: Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is a common and life-threatening infection that imposes up to 30% mortality even when appropriate therapy is used. Despite in vitro efficacy determined by minimum inhibitory concentration (MIC) breakpoints, antibiotics often fail to resolve these infections in vivo, resulting in persistent MRSA bacteremia. Recently, several genetic, epigenetic, and proteomic correlates of persistent outcomes have been identified. However, the extent to which single variables or their composite patterns operate as independent predictors of outcome or reflect shared underlying mechanisms of persistence is unknown. To explore this question, we employed a tensor-based integration of host transcriptional and cytokine datasets across a well-characterized cohort of patients with persistent or resolving MRSA bacteremia outcomes. This method yielded high correlative accuracy with outcomes and immunologic signatures united by transcriptomic and cytokine datasets. Results reveal that patients with persistent MRSA bacteremia exhibit signals of granulocyte dysfunction, suppressed antigen presentation, and deviated lymphocyte polarization. In contrast, patients with resolving bacteremia heterogeneously exhibit correlates of robust antigen-presenting cell trafficking and enhanced neutrophil maturation corresponding to appropriate T lymphocyte polarization and B lymphocyte response. These results suggest that transcriptional and cytokine correlates of persistent versus resolving bacteremia outcomes are complex and may not be disclosed by conventional modeling. In this respect, a tensor-based integration approach may help to reveal consensus molecular and cellular mechanisms and their biological interpretation.

INTRODUCTION: Staphylococcus aureus bacteremia (SAB) is a life-threatening infection particularly involving methicillin-resistant S. aureus (MRSA). In contrast to resolving MRSA bacteremia (RB), persistent MRSA bacteremia (PB) blood cultures remain positive despite appropriate antibiotic treatment. Host immune responses distinguishing PB vs. RB outcomes are poorly understood. Here, integrated transcriptomic, IL-10 cytokine levels, and genomic analyses sought to identify signatures differentiating PB vs. RB outcomes. METHODS: Whole-blood transcriptomes of propensity-matched PB (n=28) versus RB (n=30) patients treated with vancomycin were compared in one independent training patient cohort. Gene expression (GE) modules were analyzed and prioritized relative to host IL-10 cytokine levels and DNA methyltransferase-3A (DNMT3A) genotype. RESULTS: Differential expression of T and B lymphocyte gene expression early in MRSA bacteremia discriminated RB from PB outcomes. Significant increases in effector T and B cell signaling pathways correlated with RB, lower IL-10 cytokine levels and DNMT3A heterozygous A/C genotype. Importantly, a second PB and RB patient cohort analyzed in a masked manner demonstrated high predictive accuracy of differential signatures. DISCUSSION: Collectively, the present findings indicate that human PB involves dysregulated immunity characterized by impaired T and B cell responses associated with excessive IL-10 expression in context of the DNMT3A A/A genotype. These findings reveal distinct immunologic programs in PB vs. RB outcomes, enable future studies to define mechanisms by which host and/or pathogen drive differential signatures and may accelerate prediction of PB outcomes. Such prognostic assessment of host risk could significantly enhance early anti-infective interventions to avert PB and improve patient outcomes.

This work investigates the AC conductivity, impedance spectroscopy, and modulus formulation of varied compositions of glass samples within the modified borovanadate glassy system, synthesized using the melt-quenching technique. Up to 10 mol% of BaO, the AC conductivity shows a rising trend as BaO content rises; however, for x = 15&20 mol%, there is a drop. The Almond West model fits the experimental data of ac conductivity and parameters such as crossover frequency, frequency exponent (s), and direct current conductivity are retrieved. All samples feature a CBH conduction mechanism at varying frequencies, except for VBa1, which has a small polaron quantum mechanical mechanism. There is good agreement in the activation energy derived from conductivity (0.565–0.742 eV), electric modulus (0.526–0.616 eV), and impedance research (0.530–0.743 eV). Dielectric studies reveal non-Debye-type behavior. According to impedance formalism, electric conduction occurs through Ba2+ ions and electron/polarons. This characteristic renders the glasses well-suited for energy storage devices. [ABSTRACT FROM AUTHOR]

The quaternary glass system 60TeO2-(25−x)Bi2O3-15B2O3-xKCl has been prepared by the melt-quenching process with x ranging from 0 to 20 mol%. X-ray diffraction patterns confirmed the amorphous nature of the synthesized glasses, showing no sharp crystalline peaks. The techniques field emission scanning electron microscopy and energy dispersive X-ray spectroscopy provide information about the surface morphology and elemental composition of the synthesized glass system, respectively. Physical parameters such as density, molar volume, ion concentration, interionic distance, polaron radius, and cation field strength were calculated to determine structural stability. Density and molar volume both decrease with an increase in KCl content. Oxygen packing density decreases with increasing KCl concentration, indicating a rise in non-bridging oxygen atoms. Using differential scanning calorimetry, the glass transition temperature (Tg) was calculated. Its value is found to decrease as the KCl content increases. FTIR and Raman spectra indicate the transformation of TeO4 units into TeO3 units and BO4 units into BO3 units with an increase in KCl content. The diffuse reflectance spectra method is used to study optical parameters such as optical band gap, cut-off wavelength, Urbach energy, refractive index, and metallization criteria. The optical indirect band gap energies (Eopt) range from 2.78 to 3.31 eV and are calculated by applying Tauc's relation. On the other hand, the values of the urbach energy (EU) vary from 0.289 to 0.183 eV, indicating disorderliness or defects in the glass samples decrease with increasing KCl content. The synthesized glasses can be considered for non-linear optical applications since their metallization criterion (M) values ranged from 0.373 to 0.407. The dielectric parameters of the glasses were calculated on a frequency scale of 10–1 to 106 Hz by varying the temperature from 453 to 553 K. Dielectric analysis of the as-prepared glasses shows the non-Debye type behavior. [ABSTRACT FROM AUTHOR]

In the present study, lead-modified bismuth borovanadate glasses were synthesized using the conventional melt-quench technique, maintaining a fixed composition of (50 − x)V2O5–40B2O3–10Bi2O3–xPbO, where x ranged from 5 to 25 mol% in 5 mol% increments. To confirm the amorphous nature of the samples, X-ray diffraction was utilized. Several physical properties, including density (ρg) (3.55 to 4.41 g/cm3), molar volume (Vm) (47.21 to 39.83 cm3/mol), crystalline volume (Vc) (42.09 to 35.94 cm3/mol), and oxygen packing density (OPD) (80.49 to 75.32 g-atom/l), were examined and found to exhibit composition-dependent variations. Additionally, various other parameters were determined, including interionic distance (Ri) (1.16 to 0.65 cm−1), lead yield field (F) (0.38 to 1.21 cm−2), concentrations of Pb2+ ions (N) (ranging from 0.64 to 3.78 ions/cm3), and Polaron radius (Rp) (ranging from 4.68 to 2.60 cm−1). The analysis of DSC thermograms revealed a positive correlation between the concentration of lead oxide and the glass transition temperature (Tg), which varied from 254 to 295 ºC. This suggests an improvement in the thermal stability of the glass system with increasing lead oxide content. Structural investigations using infrared and Raman spectroscopy indicated that V2O5 served a dual role as a network former (with VO5 units) and as a modifier (with VO4 units). The presence of PbO and Bi2O3 as modifiers facilitated the transformation of BO3 units into BO4 units and the formation of diborovanadate ([B2V2O9]2−) groups and strong B–O–V linkages. The optical energy band gap (Eopt), determined through UV–visible spectroscopy, showed a consistent increase with the progressive incorporation of PbO. Both direct allowed (1.986 to 2.392 eV) and indirect allowed (1.582 to 2.087 eV) band gaps exhibited this rising trend. Furthermore, the prepared glasses demonstrated a high level of optical basicity (1.182 to 1.168), electronic polarizability (3.419 to 3.327) of oxide ions, third-order non-linear optical susceptibility (0.141 to 0.063 × 10–10 esu), and metallization criterion (0.281 to 0.323). These results suggest that the glasses prepared in this study have the potential for use in non-linear optical applications. [ABSTRACT FROM AUTHOR]

The goal of the current work is to identify the structural, magnetic, and optical properties of Gd-doped SnO2 nanoparticles and their potential use in the treatment of water contaminated with dye. These Gd-doped SnO2 (Gd = 0%, 0.5%, 1.5%, 3%, 5%) samples were prepared by the cost-effective sol–gel approach. XRD & FTIR were used to study structural properties and to confirm that the synthesized samples have single-phase crystalline nature. Using XRD Crystallite size have been calculated and found to be in the range 12.14–9.60 nm. Particle size obtained from HRTEM lying in the range 15.94–9.86 nm which was in well agreement with XRD. Raman, PL and XPS spectroscopy were utilized to investigate defects/oxygen vacancies in the lattice. Magnetic investigations indicate that the magnetic character of synthesized samples with maximum magnetization3.95 × 10–3 emu/g for Gd 5%. UV-DRS further showed that the band gap was reduced up to 5% Gd (Eg = 3.68 eV) in comparison to pure SnO2 (Eg = 3.81 eV) due to the formation of vacancy defects. In comparison to pure SnO2, Gd-doped SnO2 (Gd 5%) was found to have a maximum photodegradation efficiency of 95.64% in 60 min under UV irradiation for Rose Bengal dye. Henceforth, it can be concluded that SnO2 is a remarkable multifunctional material having uses in spintronic devices and as a catalyst in the degradation of organic dyes because of the improvement in the ferromagnetic character and enhancement in catalytic behavior on incorporation of rare-earth ions. [ABSTRACT FROM AUTHOR]

Introduction: Staphylococcus aureus bacteremia (SAB) is a life-threatening infection particularly involving methicillin-resistant S. aureus (MRSA). In contrast to resolving MRSA bacteremia (RB), persistent MRSA bacteremia (PB) blood cultures remain positive despite appropriate antibiotic treatment. Host immune responses distinguishing PB vs. RB outcomes are poorly understood. Here, integrated transcriptomic, IL-10 cytokine levels, and genomic analyses sought to identify signatures differentiating PB vs. RB outcomes., Methods: Whole-blood transcriptomes of propensity-matched PB (n=28) versus RB (n=30) patients treated with vancomycin were compared in one independent training patient cohort. Gene expression (GE) modules were analyzed and prioritized relative to host IL-10 cytokine levels and DNA methyltransferase-3A ( DNMT3A ) genotype., Results: Differential expression of T and B lymphocyte gene expression early in MRSA bacteremia discriminated RB from PB outcomes. Significant increases in effector T and B cell signaling pathways correlated with RB, lower IL-10 cytokine levels and DNMT3A heterozygous A/C genotype. Importantly, a second PB and RB patient cohort analyzed in a masked manner demonstrated high predictive accuracy of differential signatures., Discussion: Collectively, the present findings indicate that human PB involves dysregulated immunity characterized by impaired T and B cell responses associated with excessive IL-10 expression in context of the DNMT3A A/A genotype. These findings reveal distinct immunologic programs in PB vs. RB outcomes, enable future studies to define mechanisms by which host and/or pathogen drive differential signatures and may accelerate prediction of PB outcomes. Such prognostic assessment of host risk could significantly enhance early anti-infective interventions to avert PB and improve patient outcomes., Competing Interests: VGF reports Grant/Research Support: MedImmune, Cerexa/Forest/Actavis/Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Cubist/Merck; Medical Biosurfaces; Locus; Affinergy; Contrafect; Karius; Genentech, Regeneron, BasileaPaid Consultant: Pfizer, Novartis Galderma, Novadigm, Durata, Debiopharm, Genentech, Achaogen, Affinium, Medicines Co., Cerexa, Tetraphase, Trius, MedImmune, Bayer, Theravance, Cubist, Basilea, Affinergy, Janssen, xBiotech, Contrafect, Regeneron, Basilea, Destiny. Membership: Merck Co-Chair V710 Vaccine. Educational fees: Green Cross, Cubist, Cerexa, Durata, Theravance; Debiopharm. Royalties: UpToDate. MRY is a founder and shareholder of NovaDigm Therapeutics, Inc., which develops vaccines and immunotherapeutics targeting multi-drug-resistant pathogens, including S. aureus. He has received research funding from the U.S. National Institutes of Health and the U.S. Department of Defense and has received honoraria for educational activities or consultation from Alexion/AstraZeneca, Genentech-Roche and Horizon/Amgen. EFR is on the board of Federation of Clinical Immunology Societies. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (Copyright © 2024 Parmar, Pickering, Ahn, Rossetti, Gjertson, Ruffin, Chan, Fowler, Yeaman, Reed and MRSA Systems Immunology Group.)

Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is a common and life-threatening infection that imposes up to 30% mortality even when appropriate therapy is used. Despite in vitro efficacy determined by minimum inhibitory concentration breakpoints, antibiotics often fail to resolve these infections in vivo, resulting in persistent MRSA bacteremia. Recently, several genetic, epigenetic, and proteomic correlates of persistent outcomes have been identified. However, the extent to which single variables or their composite patterns operate as independent predictors of outcome or reflect shared underlying mechanisms of persistence is unknown. To explore this question, we employed a tensor-based integration of host transcriptional and cytokine datasets across a well-characterized cohort of patients with persistent or resolving MRSA bacteremia outcomes. This method yielded high correlative accuracy with outcomes and immunologic signatures united by transcriptomic and cytokine datasets. Results reveal that patients with persistent MRSA bacteremia (PB) exhibit signals of granulocyte dysfunction, suppressed antigen presentation, and deviated lymphocyte polarization. In contrast, patients with resolving bacteremia (RB) heterogeneously exhibit correlates of robust antigen-presenting cell trafficking and enhanced neutrophil maturation corresponding to appropriate T lymphocyte polarization and B lymphocyte response. These results suggest that transcriptional and cytokine correlates of PB vs. RB outcomes are complex and may not be disclosed by conventional modeling. In this respect, a tensor-based integration approach may help to reveal consensus molecular and cellular mechanisms and their biological interpretation., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)