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Genomic and phenotypic characterization of plasmid-mediated extensively drug-resistant Salmonella Typhi from Lahore Pakistan carrying IncY IncQ1 and IncC replicons
Abstract Antimicrobial resistance and emergence of MDR and XDR Salmonella enterica subsp. enterica serovar Typhi is a major threat in Pakistan. Failure of treatment with conventional antibiotics leads to importance of exploring alternative treatment plan. Therefore, this study aimed to check the resistance patterns and delineate the molecular basis of resistance among clinical isolates of S . typhi. 384 clinical isolates of S. Typhi were processed according to standard microbiological techniques. Antimicrobial sensitivity testing was performed by using VITEK-2 compact system. DNA was extracted and Gene specific PCR was done to confirm XDR S. Typhi. Whole Genome Sequencing was performed and Plasmidfinder software was used for plasmids identification. Among 382 S. Typhi, males were predominant which accounted for 61.7% and 43.2% samples were from age group of less than 10 years. Carbapenems and azithromycin showed 100% sensitivity. XDR S. Typhi accounted for 38% of total isolates. Most commonly found plasmids were IncQ1, IncY and IncC. Whole genome assemblies generated using SPAdes v3.15.5 achieved a mean coverage depth of ~ 125 × , revealing the principal plasmid replicons IncQ1, IncY, IncC, and IncA/C2 associated with multidrug resistance in Salmonella Typhi. XDR Salmonella Typhi poses a significant challenge in the treatment of typhoid fever and serious threat for public health. Horizontal transfer of plasmids among Enterobacterales contributes to the emergence and maintenance of XDR S. Typhi.
High-accuracy fatigue life prediction and early fracture warning for ferromagnetic metals via spin correlation amplification
Effects of UV-C irradiation and Spirulina priming on physiology and sanitary quality in creole maize
Author Correction: Organocatalytic enantioselective [2π + 2σ] cycloaddition reactions of bicyclo[1.1.0]butanes with α,β-unsaturated aldehydes
Hybrid attention optimized hierarchical multiscale transformer architecture for image super-resolution
Impact of NPAS2 on mPFC dopamine synthesis and nap behavior
Enhanced power management in PV-Integrated hybrid energy storage systems using fuzzy 2DOF-PI control optimized by hippopotamus algorithm
Abstract This study presents an advanced control strategy for a standalone photovoltaic (PV) system integrated with a hybrid energy storage system (HESS) comprising batteries and supercapacitors (SCs). The proposed system employs a novel Fuzzy Logic-based Two-Degree-of-Freedom Proportional-Integral (Fuzzy 2DOF-PI) controller, optimized using the Hippopotamus Optimization (HO) algorithm, to enhance power management and stability. The batteries address long-term energy demands, while SCs handle instantaneous power fluctuations, mitigating stress on the batteries and extending their lifespan. The control strategy ensures optimal power distribution, maintains DC bus voltage stability, and prevents battery overcharging by regulating the State of Charge (SOC) within safe limits. The system’s performance is validated through MATLAB/Simulink simulations under varying solar irradiance and load conditions. Comparative analyses with classical PI, Fuzzy PI-based Teaching-Learning-Based Optimization (TLBO), and Particle Swarm Optimization (PSO) demonstrate the better dynamic response, reduced transient time, and minimized overshoot of the proposed approach. Results indicate improvements of at least 15% in peak overshoot and 10% in transient duration, highlighting the robustness and efficiency of the Fuzzy 2DOF-PI controller in hybrid energy storage applications.
Toroidicity as a route towards non-volatile quaternary memory in antiferromagnets
Sex-related differences in blood concentrations and emergence profiles following total intravenous anesthesia with remimazolam and remifentanil
Abstract Remimazolam is a novel, short-acting benzodiazepine, which is characterized by rapid onset and quick recovery. The clinical efficacy and metabolism of many intravenous anesthetics are known to be influenced by sex; however, the effects of sex on the anesthetic efficacy and metabolism of remimazolam remain unclear. This prospective observational study examined sex-related differences in pharmacokinetics and emergence profiles after total intravenous anesthesia was induced with remimazolam and remifentanil in patients undergoing oral and maxillofacial surgery. Thirty-five American Society of Anesthesiologists Physical Status 1 adults (19 females, 16 males), aged 18–49 years, received standardized dosing based on their actual body weights. Serum remimazolam concentrations were measured at the end of administration and immediately before extubation using high-performance liquid chromatography. Although the emergence time did not differ significantly between the sexes, the mean emergence time of the females was approximately 80 s shorter. Serum remimazolam concentrations were significantly lower in females at both measurement time points ( p < 0.001). This may suggest that remimazolam is metabolized more rapidly in women. Although these sex-related pharmacokinetic differences did not affect the time to awakening under combined remimazolam and remifentanil anesthesia, clinicians should be aware of potential sex differences in the pharmacokinetics of remimazolam.
Author Correction: Generalizable and scalable protein stability prediction with rewired protein generative models
Artificial intelligence driven approach for securing backup data and enhancing cyber resilience in sustainable smart infrastructure
Single-cell multi-omic analysis of mitochondrial mutational mosaicism and dynamics
Abstract Mitochondrial DNA (mtDNA) mutations occur more frequently than nuclear mutations and are associated with various diseases. While single-cell sequencing enables mtDNA variant heteroplasmy analysis, a holistic view of mtDNA mutational landscapes in individual cells has remained limited. Here, we leverage mitochondrial single-cell ATAC-seq and mtDNA-hypermutated POLG D274A knock-in HEK293 cell lines to introduce two metrics—single-cell mtDNA mutations per million base pairs (scmtMPM) and heteroplasmy-weighted mitochondrial local constraint scores (scwMSS)—to capture cellular mutational loads and somatic mosaicism. We demonstrate that individual POLG D274A cells exhibit complex mutational landscapes, with pathogenic mutations and truncating variants only present at subthreshold levels, indicative of their negative selection. In human healthy donors and mitochondriopathy patients, we identify constrained mutations in complex I, highlighting previously unrecognized mtDNA mutational landscape heterogeneity present on the single-cell level. Overall, scmtMPM and scwMSS provide a framework to investigate fundamental properties of mitochondrial genetics, disease, and somatic mosaicism.
Protective effect of iron against cadmium-induced lesions in rat testis via downregulation of NQO1/Nrf2 and NF-κB
Condensin accelerates long-range intra-chromosomal interactions
Energy absorption and rebound behavior of 3D-printed TPU lattice structures
Space and space-time topologies in a type-II hyperbolic lattice
Correction to “Dual‐Targeting Biomimetic Semiconducting Polymer Nanocomposites for Amplified Theranostics of Bone Metastasis”
Perineal muscle strength as a predictor of stress urinary incontinence among young parous women in Mangaluru India
Implantable soft bladder-machine interface for neurogenic bladder dysfunction
Decoding clone evolution in HER2 amplified breast cancer through single-cell and spatial transcriptomics analysis of copy number variations
Abstract HER2-positive breast cancer exhibits marked genomic instability and heterogeneity, yet the clonal architecture and copy number variation (CNV) dynamics between ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC), remain poorly understood. We analyzed single-cell RNA sequencing data from 14 HER2-positive breast cancer patients and spatial transcriptomics from 8 patients. CNVs were inferred to evaluate genomic alterations and reconstruct tumor subclone evolutionary trajectories. Survival analyses were performed on CNV-correlated transcripts. We identified 68,064 cells and 4,764 spatial transcriptomic spots, and observed early and pervasive CNV events in DCIS. IDC exhibiting a higher CNV burden supported the hypothesis of progressive genomic instability during tumor evolution. Shared CNV regions across DCIS and IDC suggested the common clonal origin, favoring a multi-threaded evolutionary model. Amplifications in chromosome 17q12-21 were associated with poor prognosis. CNV-driven clonal evolution probably originates at early stages of HER2-positive breast cancer and persists through disease progression. Early CNV events may serve as predictive biomarkers and potential intervention targets to prevent disease advancement.