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Scientific Reports Jun 2024Nasally colonized staphylococci carry antibiotic resistance genes and may lead to serious opportunistic infections. We are investigating nasal carriage of Staphylococcus...
Nasally colonized staphylococci carry antibiotic resistance genes and may lead to serious opportunistic infections. We are investigating nasal carriage of Staphylococcus aureus and Staphylococci other than S. aureus (SOSA) among young volunteers in Egypt to determine their risk potential. Nasal swabs collected over 1 week in June 2019 from 196 volunteers were cultured for staphylococcus isolation. The participants were interviewed to assess sex, age, general health, hospitalization and personal hygiene habits. Identification was carried out using biochemical tests and VITEK 2 automated system. Disc diffusion and minimum inhibitory concentration tests were performed to determine antibiotic susceptibility. Screening for macrolide resistance genes (ermA, ermB, ermC, ermT and msrA) was performed using polymerase chain reaction. Thirty four S. aureus and 69 SOSA were obtained. Multi-drug resistance (MDR) was detected among most staphylococcal species, ranging from 30.77% among S. hominis to 50% among S. epidermidis. Phenotypic resistance to all tested antibiotics, except for linezolid, was observed. Susceptibility to rifampicin, vancomycin and teicoplanin was highest. ermB showed the highest prevalence among all species (79.41% and 94.2% among S. aureus and SOSA, respectively), and constitutive macrolide-lincosamide-streptogramin B (MLS) resistance was equally observed in S. aureus and SOSA (11.11% and 16.22%, respectively), whereas inducible MLS resistance was more often found in S. aureus (77.78% and 43.24%, respectively). The species or resistance level of the carried isolates were not significantly associated with previous hospitalization or underlying diseases. Although over all colonization and carriage of resistance genes are within normal ranges, the increased carriage of MDR S. aureus is alarming. Also, the fact that many macrolide resitance genes were detected should be a warning sign, particularly in case of MLS inducible phenotype. More in depth analysis using whole genome sequencing would give a better insight into the MDR staphylococci in the community in Egypt.
Topics: Humans; Egypt; Female; Male; Staphylococcus; Microbial Sensitivity Tests; Staphylococcal Infections; Anti-Bacterial Agents; Adult; Phenotype; Young Adult; Genotype; Staphylococcus aureus; Drug Resistance, Multiple, Bacterial; Adolescent
PubMed: 38937465
DOI: 10.1038/s41598-024-60924-8 -
ENeuro Jun 2024Ghrelin is a stomach-derived hormone that increases feeding and is elevated in response to chronic psychosocial stressors. The effects of ghrelin on feeding are mediated...
Ghrelin is a stomach-derived hormone that increases feeding and is elevated in response to chronic psychosocial stressors. The effects of ghrelin on feeding are mediated by the binding of ghrelin to the growth hormone secretagogue receptor (GHSR), a receptor located in hypothalamic and extra-hypothalamic regions important for regulating food intake and metabolic rate. The ability of ghrelin to enter the brain, however, seems to be restricted to circumventricular organs like the median eminence and the brain stem area postrema (AP), whereas ghrelin does not readily enter other GHSR expressing regions like the ventral tegmental area (VTA). Interestingly, social stressors result in increased blood brain barrier permeability, and this could therefore facilitate the entry of ghrelin into the brain. To investigate this, we exposed mice to social defeat stress for 21 days, then peripherally injected a Cy5-labelled biologically active ghrelin analogue. Results demonstrate that chronically stressed mice exhibit higher Cy5-ghrelin fluorescence in several hypothalamic regions in addition to the ARC, including the hippocampus and midbrain. Furthermore, Cy5-ghrelin injections resulted in increased FOS expression in regions associated with the reward system in the chronically stressed mice. Further histologic analyses identified a reduction in branching of hypothalamic astrocytes in the ARC-median eminence junction, suggesting increased blood-brain barrier permeability. These data support the hypothesis that during metabolically challenging conditions like chronic stress, ghrelin may be more able to cross the blood brain barrier and diffuse throughout the brain to target GHSR expressing brain regions away from circumventricular organs. Ghrelin is secreted in response to negative energy balance states including stress and is associated with changes in food intake and energy balance. The receptors for ghrelin are found throughout the brain but ghrelin seems to only reach circumventricular regions where the blood brain barrier is more porous. In this paper we demonstrate that chronic social defeat stress increases brain permeability to ghrelin to allow for entry and activation of target sites in the mesolimbic dopaminergic system that are not accessible to ghrelin under non-stress conditions. Overall, these results provide for an explanation as to how ghrelin can access the mesolimbic dopaminergic system in a state dependent manner.
PubMed: 38937108
DOI: 10.1523/ENEURO.0093-24.2024 -
Journal of Cardiovascular Magnetic... Jun 2024In-vivo diffusion tensor CMR (DT-CMR) is an emerging technique for microstructural tissue characterisation in the myocardium. Most studies are performed at 3T, where...
BACKGROUND
In-vivo diffusion tensor CMR (DT-CMR) is an emerging technique for microstructural tissue characterisation in the myocardium. Most studies are performed at 3T, where higher signal to noise ratio (SNR) should benefit this signal starved method. However, a few studies have suggested that DT-CMR is possible at 1.5T, where EPI artefacts may be less severe and 1.5T hardware is more widely available.
METHODS
We recruited 20 healthy volunteers and performed mid-ventricular short axis DT-CMR at 1.5 T and 3 T. Acquisitions were performed at peak systole and end-diastole using both stimulated echo acquisition mode (STEAM) and motion compensated spin-echo (MCSE) sequences at matched spatial resolutions. DT-CMR parameters were averaged over the LV and compared between 1.5 T and 3 T sequences using both datasets with and without the blow reference data included.
RESULTS
Eleven (1.5T) and 12 (3T) diastolic MCSE acquisitions were rejected as the helix angle (HA) demonstrated <50% normal appearance circumferentially or the acquisition was abandoned due to poor image quality; a maximum of one acquisition was rejected for other datasets. Subjective HA map quality was significantly better at 3T than 1.5T for STEAM (p<0.05), but not for MCSE and other DT-CMR quality measures were consistent with improvements in STEAM at 3T over 1.5T. When b data was excluded, no significant differences in mean diffusivity were observed between field strengths, but fractional anisotropy was significantly higher at 1.5T than 3T for STEAM systole (p<0.05). Absolute second eigenvector orientation (E2A, sheetlet angle) was significantly higher at 1.5T than 3T for MCSE systole and STEAM diastole, but significantly lower for STEAM systole (all p<0.05). Transmural HA distribution was less steep at 1.5T than 3T for STEAM diastole data (p<0.05). SNR in the b images was higher at 3T than 1.5T for all acquisitions (p<0.05).
CONCLUSION
While 3T provides benefits in terms of SNR, both STEAM and MCSE can be performed at 1.5T. However, MCSE is unreliable in diastole at both field strengths and STEAM benefits from the improved SNR at 3T over 1.5T. Future clinical research studies may be able to leverage the wider availability of 1.5T CMR hardware where MCSE acquisitions are desirable.
PubMed: 38936803
DOI: 10.1016/j.jocmr.2024.101052 -
PLoS Computational Biology Jun 2024Therapeutic interventions are designed to perturb the function of a biological system. However, there are many types of proteins that cannot be targeted with...
Therapeutic interventions are designed to perturb the function of a biological system. However, there are many types of proteins that cannot be targeted with conventional small molecule drugs. Accordingly, many identified gene-regulatory drivers and downstream effectors are currently undruggable. Drivers and effectors are often connected by druggable signaling and regulatory intermediates. Methods to identify druggable intermediates therefore have general value in expanding the set of targets available for hypothesis-driven validation. Here we identify and prioritize potential druggable intermediates by developing a network perturbation theory, termed NetPert, for response functions of biological networks. Dynamics are defined by a network structure in which vertices represent genes and proteins, and edges represent gene-regulatory interactions and protein-protein interactions. Perturbation theory for network dynamics prioritizes targets that interfere with signaling from driver to response genes. Applications to organoid models for metastatic breast cancer demonstrate the ability of this mathematical framework to identify and prioritize druggable intermediates. While the short-time limit of the perturbation theory resembles betweenness centrality, NetPert is superior in generating target rankings that correlate with previous wet-lab assays and are more robust to incomplete or noisy network data. NetPert also performs better than a related graph diffusion approach. Wet-lab assays demonstrate that drugs for targets identified by NetPert, including targets that are not themselves differentially expressed, are active in suppressing additional metastatic phenotypes.
PubMed: 38935814
DOI: 10.1371/journal.pcbi.1012195 -
PloS One 2024Under the long-term effect of mineral resource exploitation, especially open-pit mining, ecosystems are severely disturbed. Constructing and optimizing urban ecological...
Under the long-term effect of mineral resource exploitation, especially open-pit mining, ecosystems are severely disturbed. Constructing and optimizing urban ecological networks influenced by open-pit mines based on mine-city coordination helps integrate ecological restoration and the construction of urban ecological environments. We applied an InVEST model to Fushun City to evaluate urban ecosystem services under the influence of large open-pit mines. Twenty-one key patches important for maintaining landscape connectivity were screened as the ecological sources in the network, from which ecological resistance surfaces were constructed by combining the impacts of mines on the environment. Minimum cumulative resistance (MCR) and gravity models were then used to extract and classify ecological corridors favorable to species migration and diffusion. Fushun City had large spatial differences in ecosystem service functions, with high-value areas concentrated in the forest-rich Dongzhou District and the northern Shuncheng District. Under the influence of open-pit mining, the ecosystem service capacity of the region south of the Hunhe River was poor and lacked ecological sources. Urban ecological resistance surfaces reached a maximum in the open-pit mining area, and 210 ecological corridors were estimated using the MCR model, of which 46 were important. Only two corridors crossed the West and East open pit, forming two "ecological fracture surfaces." The Dongzhou and eastern Shuncheng districts had complex network structures and stable ecological environments. In contrast, the central and southern parts of Fushun City lacked ecological corridors owing to the influence of mining pits and gangue mountains, had simple network structures, and low connectivities with other sources. Combined with Fushun City's development plan, we propose that ecological network optimization should add new ecological source sites, reconstruct and repair ecological corridors, and upgrade ecological breakpoints. This study provides reference and basis for ecological network research in mining cities influenced by open-pit mines.
Topics: Mining; China; Ecosystem; Cities; Conservation of Natural Resources; Models, Theoretical
PubMed: 38935690
DOI: 10.1371/journal.pone.0303016 -
PloS One 2024Monitoring and improving the quality of sleep are crucial from a public health perspective. In this study, we propose a change-point detection method using diffusion...
Monitoring and improving the quality of sleep are crucial from a public health perspective. In this study, we propose a change-point detection method using diffusion maps for a more accurate detection of respiratory arrest points. Conventional change-point detection methods are limited when dealing with complex nonlinear data structures, and the proposed method overcomes these limitations. The proposed method embeds subsequence data in a low-dimensional space while considering the global and local structures of the data and uses the distance between the data as the score of the change point. Experiments using synthetic and real-world contact-free sensor data confirmed the superiority of the proposed method when dealing with noise, and it detected apnea events with greater accuracy than conventional methods. In addition to improving sleep monitoring, the proposed method can be applied in other fields, such as healthcare, manufacturing, and finance. This study will contribute to the development of advanced monitoring systems that adapt to diverse conditions while protecting privacy.
Topics: Humans; Sleep Apnea Syndromes; Polysomnography; Algorithms; Monitoring, Physiologic
PubMed: 38935677
DOI: 10.1371/journal.pone.0306139 -
MSystems Jun 2024causes both hospital- and community-acquired infections in humans worldwide. Due to the high incidence of infection, is also one of the most sampled and sequenced...
UNLABELLED
causes both hospital- and community-acquired infections in humans worldwide. Due to the high incidence of infection, is also one of the most sampled and sequenced pathogens today, providing an outstanding resource to understand variation at the bacterial subspecies level. We processed and downsampled 83,383 public Illumina whole-genome shotgun sequences and 1,263 complete genomes to produce 7,954 representative substrains. Pairwise comparison of average nucleotide identity revealed a natural boundary of 99.5% that could be used to define 145 distinct strains within the species. We found that intermediate frequency genes in the pangenome (present in 10%-95% of genomes) could be divided into those closely linked to strain background ("strain-concentrated") and those highly variable within strains ("strain-diffuse"). Non-core genes had different patterns of chromosome location. Notably, strain-diffuse genes were associated with prophages; strain-concentrated genes were associated with the vSaβ genome island and rare genes (<10% frequency) concentrated near the origin of replication. Antibiotic resistance genes were enriched in the strain-diffuse class, while virulence genes were distributed between strain-diffuse, strain-concentrated, core, and rare classes. This study shows how different patterns of gene movement help create strains as distinct subspecies entities and provide insight into the diverse histories of important functions.
IMPORTANCE
We analyzed the genomic diversity of , a globally prevalent bacterial species that causes serious infections in humans. Our goal was to build a genetic picture of the different strains of and which genes may be associated with them. We reprocessed >84,000 genomes and subsampled to remove redundancy. We found that individual samples sharing >99.5% of their genome could be grouped into strains. We also showed that a portion of genes that are present in intermediate frequency in the species are strongly associated with some strains but completely absent from others, suggesting a role in strain specificity. This work lays the foundation for understanding individual gene histories of the species and also outlines strategies for processing large bacterial genomic data sets.
PubMed: 38934646
DOI: 10.1128/msystems.00143-24 -
Haematologica Jun 2024Macrophages are one of the key mediators of the therapeutic effects exerted by monoclonal antibodies, such as the anti-CD19 antibody tafasitamab, approved in combination...
Macrophages are one of the key mediators of the therapeutic effects exerted by monoclonal antibodies, such as the anti-CD19 antibody tafasitamab, approved in combination with lenalidomide for the treatment of relapsed or refractory (r/r) diffuse large B cell lymphoma (DLBCL). However, antibody-dependent cellular phagocytosis (ADCP) in the tumor microenvironment can be counteracted by increased expression of the inhibitory receptor SIRPα on macrophages and its ligand, the immune checkpoint molecule CD47 on tumor cells. The aim of this study was to investigate the impact of the CD47-SIRPα axis on tafasitamabmediated phagocytosis and explore the potential of anti-CD47 blockade to enhance its antitumor activity. Elevated expression of both SIRPα and CD47 was observed in DLBCL patient-derived lymph node biopsies compared to healthy controls. CRISPR-mediated CD47 overexpression impacted tafasitamab-mediated ADCP in vitro and increased expression of SIRPα on macrophages correlated with decreased ADCP activity of tafasitamab against DLBCL cell lines. Combination of tafasitamab and an anti-CD47 blocking antibody enhanced ADCP activity of in vitro generated macrophages. Importantly, tafasitamab-mediated phagocytosis was elevated in combination with CD47 blockade using primary DLBCL cells and patient-derived lymphoma-associated macrophages (LAMs) in an autologous setting. Furthermore, lymphoma cells with low CD19 expression were efficiently eliminated by the combination treatment. Finally, combined treatment of tafasitamab and an anti-CD47 antibody resulted in enhanced tumor volume reduction and survival benefit in lymphoma xenograft mouse models. These findings provide evidence that CD47 blockade can enhance the phagocytic potential of tumor targeting immunotherapies such as tafasitamab and suggest there is value in exploring the combination in the clinic.
PubMed: 38934068
DOI: 10.3324/haematol.2023.284795 -
Nanoscale Advances Jun 2024Recently, MXenes have been widely investigated for use as electrodes in various ion storage batteries. In this study, ZrN, HfN and ZrHfN were explored as potential anode...
Recently, MXenes have been widely investigated for use as electrodes in various ion storage batteries. In this study, ZrN, HfN and ZrHfN were explored as potential anode materials for Ca-ion batteries. AIMD simulations predict higher structural stability for our proposed MXenes at a temperature of 300 K. The adsorption energies at the most favourable adsorption sites are 1.31, 1.33 and 1.27 eV for ZrN, HfN and ZrHfN, respectively. During the adsorption process, a significant amount of charge transfer occurs from the Ca atom to the nanosheets. DOS and PDOS analyses reveal that the adsorption of Ca atoms enhances the conductivity of the nanosheets. Moreover, the low diffusion barriers are found to be 0.076, 0.073 and 0.097 eV when the Ca atom migrates from its favourable adsorption site to a nearby site on ZrN, HfN and ZrHfN nanosheets, resulting in high charging rates. The theoretical capacities of ZrN, HfN and ZrHfN nanosheets are 1034, 561 and 707 mA h g, respectively. All the results from this study suggest that our proposed nanosheets can be potential anode materials for Ca-ion batteries. Among them, the ZrN nanosheet shows superior anodic properties for Ca-ion batteries, which is also confirmed by specific capacity, diffusion barrier and open circuit voltage calculations.
PubMed: 38933860
DOI: 10.1039/d4na00140k -
Nanoscale Advances Jun 2024Metal oxides with hollow porous structures are attractive and promising anode candidates for Li-ion batteries due to their high surface area, high loading capacity, and...
Metal oxides with hollow porous structures are attractive and promising anode candidates for Li-ion batteries due to their high surface area, high loading capacity, and low density. In this work, hierarchical hollow porous structures of nickel (Ni)-doped λ-MnO were prepared a facile, and cost-effective approach, where different amounts of Ni were introduced into MnO structures to tailor their physical and chemical properties. When the prepared Ni-doped MnO hollow structures were studied as anode materials for Li-ion batteries, the electrode showed excellent electrochemical properties, such as stable cyclability and admirable rate capability. Moreover, Ni doping significantly enhances the diffusion properties of the active materials. The material was also investigated as an anode in another high power and energy Li-ion storage device, namely, a Li-ion hybrid capacitor, which exhibited excellent comprehensive electrochemical performance in terms of good specific cell capacity of 25 mA h g at a high current density of 5 A g and achieved a maximum power density of 29 W kg (with energy density of 30 W h kg) with a long cycle life. These results indicate that the Ni-doped MnO is suitable for application as an anode material and give considerable insight into future Li-energy storage applications.
PubMed: 38933856
DOI: 10.1039/d4na00023d