Multidrug-resistant ST11-KL64 hypervirulent with multiple genes isolated from children's blood.

Introduction: Hypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKP) poses an increasing public health risk due to its high treatment difficulty and associated mortality, especially in bone marrow transplant (BMT) patients. The emergence of strains with multiple resistance mechanisms further complicates the management of these infections.

Methods: We isolated and characterized a novel ST11-KL64 hv-CRKP strain from a pediatric bone marrow transplantation patient.

Temperature Effects in Conventional and RAFT Photopolymerization.

Photochemical processes are often thought to be temperature-independent. However, photochemical polymerization involves photochemical processes such as light-driven radical generation coupled with thermal-driven reactions such as monomer propagation. The apparent activation energy of propagation, ( ), of a series of three monomers, methyl acrylate (MA), methyl methacrylate (MMA), and styrene (STY), are deduced from Arrhenius analysis of conventional and RAFT photopolymerization of these monomers across a range of corresponding temperatures.

A compliant metastructure design with reconfigurability up to six degrees of freedom.

Compliant mechanisms with reconfigurable degrees of freedom are gaining attention in the development of kinesthetic haptic devices, robotic systems, and mechanical metamaterials. However, available devices exhibit limited programmability and form-customizability, restricting their versatility. To address this gap, we propose a metastructure concept featuring reconfigurable motional freedom and tunable stiffness, adaptable to various form factors and applications.

Immunotherapy for advanced-stage squamous cell lung cancer: the state of the art and outstanding questions.

Immune-checkpoint inhibitors (ICIs) have transformed the treatment paradigm for advanced-stage squamous non-small-cell lung cancer (LUSC), a histological subtype associated with inferior outcomes compared with lung adenocarcinoma. However, only a subset of patients derive durable clinical benefit. In the first-line setting, multiple ICI regimens are available, including anti-PD-(L)1 antibodies as monotherapy, in combination with chemotherapy, or with an anti-CTLA4 antibody with or without chemotherapy.

Phase 1b/2 study of orally administered pexidartinib in combination with radiation therapy and temozolomide in patients with newly diagnosed glioblastoma.

Background: Glioblastoma (GBM) has a median survival of <2 years. Pexidartinib (PLX3397) is a small-molecule inhibitor of CSF1R, KIT, and oncogenic FTL3, which are implicated in GBM treatment resistance. Results from glioma models indicate that combining radiation therapy (RT) and pexidartinib reduces radiation resistance.

A new empirical equation for the gas/particle partitioning of OPFRs in ambient atmosphere.

Gas/particle (G/P) partitioning is a core process governing the atmospheric transport of organophosphate flame retardants (OPFRs). However, accurately predicting the G/P partition performance of OPFRs remains a challenge. In this study, four independent models were employed to estimate the characteristics of OPFR G/P partitioning within the octanol-air partition coefficient range of 4.

Accurate Intramyocardial Hemorrhage Assessment with Fast, Free-running, Cardiac Quantitative Susceptibility Mapping.

Purpose To evaluate the performance of a high-dynamic-range quantitative susceptibility mapping (HDR-QSM) cardiac MRI technique to detect intramyocardial hemorrhage (IMH) and quantify iron content using phantom and canine models. Materials and Methods A free-running whole-heart HDR-QSM technique for IMH assessment was developed and evaluated in calibrated iron phantoms and 14 IMH female canine models. IMH detection and iron content quantification performance of this technique was compared with the conventional iron imaging approaches, R2*(1/T2*) maps, using measurements from ex vivo imaging as the reference standard.

Enzymatic hydrolysis processing of soybean meal altered its structure and protein digestive dynamics in pigs.

Introduction: The study evaluated the enzymatic hydrolysis processing on physicochemical properties and protein digestive dynamics of soybean meal (SBM), as well as the relationship between protein secondary structure and digestive parameters was established.

Methods: Scanning Electron Microscopy (SEM) and Fourier Transform Infrared Spectroscopy (FTIR) were employed to analyze the microstructure and protein structure of the SBM and enzymatic hydrolysis processed soybean meal (ESBM). SBM and ESBM were incubated with pepsin at pH 3.

Nationwide, Couple-Based Genetic Carrier Screening.

Background: Genomic sequencing technology allows for identification of reproductive couples with an increased chance, as compared with that in the general population, of having a child with an autosomal recessive or X-linked genetic condition.

Methods: We investigated the feasibility, acceptability, and outcomes of a nationwide, couple-based genetic carrier screening program in Australia as part of the Mackenzie's Mission project. Health care providers offered screening to persons before pregnancy or early in pregnancy.

Racial Disparities in Preoperative Breast MRI Use and Surgical Margin Outcomes among Patients with Recently Diagnosed Breast Cancer.

Purpose To evaluate racial disparities in preoperative breast MRI use and surgical margin outcomes among patients with recently diagnosed breast cancer. Materials and Methods This retrospective study included patients with breast cancer who presented to a single cancer center between 2008 and 2020, underwent breast surgery, and self-identified as White or Black. Patients were divided into MRI or no-MRI cohorts based on preoperative MRI use.

HTLV-1 infected T cells cause bone loss via small extracellular vesicles.

Adult T cell leukaemia (ATL), caused by infection with human T- lymphotropic virus type 1 (HTLV-1), is often complicated by hypercalcemia and osteolytic lesions. Therefore, we studied the communication between patient-derived ATL cells (ATL-PDX) and HTLV-1 immortalized CD4+ T cell lines (HTLV/T) with osteoclasts and their effects on bone mass in mice. Intratibial inoculation of some HTLV/T leads to a profound local decrease in bone mass similar to marrow-replacing ATL-PDX, despite the fact that few HTLV/T cells persisted in the bone.

Sacubitril/Valsartan in Pediatric Heart Failure (PANORAMA-HF): A Randomized, Multicenter, Double-Blind Trial.

Background: Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), is an established treatment for heart failure (HF) with reduced left ventricular ejection fraction. It has not been rigorously compared with angiotensin-converting enzyme inhibitors in children. PANORAMA-HF (Prospective Trial to Assess the Angiotensin Receptor Blocker Neprilysin Inhibitor LCZ696 Versus Angiotensin-Converting Enzyme Inhibitor for the Medical Treatment of Pediatric HF) is a randomized, double-blind trial that evaluated the pharmacokinetics and pharmacodynamics (PK/PD), safety, and efficacy of sacubitril/valsartan versus enalapril in children 1 month to <18 years of age with HF attributable to systemic left ventricular systolic dysfunction (LVSD).

Protein is expressed in all major organs after intravenous infusion of mRNA-lipid nanoparticles in swine.

delivery of mRNA is promising for the study of gene expression and the treatment of diseases. Lipid nanoparticles (LNPs) enable efficient delivery of mRNA constructs, but protein expression has been assumed to be limited to the liver. With specialized LNPs, delivery to extrahepatic tissue occurs in small animal models; however, it is unclear if global delivery of mRNA to all major organs is possible in humans because delivery may be affected by differences in innate immune response and relative organ size.

Monocytes Reprogrammed by 4-PBA Potently Contribute to the Resolution of Inflammation and Atherosclerosis.

Background: Chronic inflammation initiated by inflammatory monocytes underlies the pathogenesis of atherosclerosis. However, approaches that can effectively resolve chronic low-grade inflammation targeting monocytes are not readily available. The small chemical compound 4-phenylbutyric acid (4-PBA) exhibits broad anti-inflammatory effects in reducing atherosclerosis.

An Evaluation of Sex-Specific Pharmacokinetics and Bioavailability of Kokusaginine: An In Vitro and In Vivo Investigation.

Kokusaginine is a bioactive ingredient extracted from L., which has a range of biological activities. Its pharmacokinetic (PK) properties are particularly important for clinical applications; however, they have not been fully elucidated.

Global Seroprevalence of Tick-Borne Encephalitis Antibodies in Humans, 1956-2022: A Literature Review and Meta-Analysis.

Despite the availability of tick-borne encephalitis (TBE) vaccines, the incidence of TBE is increasing. To understand the historical patterns of infection, we conducted a global meta-analysis of studies before December 2023 reporting human antibody prevalence against TBEV (TBE virus) among general or high-risk population groups stratified by country, collection year, serological method, and vaccination status. Pooled data were compared within groups over time by random-effects modeling.

Exploring K values smaller than unity in remoxipride: A physiologically-based CNS model approach highlighting brain metabolism in drugs with passive blood-brain barrier transport.

(aim): K values are crucial indicators of drug distribution into the brain, representing the steady-state relationship between unbound concentrations in plasma and in brain extracellular fluid (brainECF). K values < 1 are often interpreted as indicators of dominant active efflux transport processes at the blood-brain barrier (BBB). However, the potential impact of brain metabolism on this value is typically not addressed.

Partition coefficient screening - An effective approach for finding the best conditions for byproduct removal as demonstrated by a bispecific antibody purification case.

In recombinant protein purification, differences in isoelectric point (pI)/surface charge and hydrophobicity between the product and byproducts generally form the basis for separation. For bispecific antibodies (bsAbs), in many cases the physicochemical difference between product and byproducts is subtle, making byproduct removal considerably challenging. In a previous report, with a bsAb case study, we showed that partition coefficient (K) screening for the product and byproducts under various conditions facilitated finding conditions under which effective separation of two difficult-to-remove byproducts was achieved by anion exchange (AEX) chromatography.

Economic evaluation of hepatocellular carcinoma surveillance in chronic hepatitis B patients with virological remission.

Background: Subsequent risk of hepatocellular carcinoma (HCC) persists in chronic hepatitis B (CHB) patients with virological remission. We aimed to assess the cost-effectiveness of HCC surveillance in those patients and determine appropriate age to commence or discontinue surveillance.

Methods: We developed an individual-based state transition model, simulating the advancement of HCC in CHB patients with virological remission.