Integration of personalised ultrasensitive ctDNA monitoring of patients with metastatic breast cancer to reduce imaging requirements.

Circulating tumour DNA (ctDNA) is an emerging biomarker for monitoring cancers. The personalised disease monitoring in metastatic breast cancer (PDM-MBC) study is an ongoing study instigated to evaluate ctDNA as a biomarker to individualise imaging requirements in patients with MBC. Patients receiving first-line endocrine therapy (aromatase inhibitor + cyclin-dependent kinase 4/6 inhibitor) had plasma samples collected pre-treatment, weeks 2 and 4, and concurrently with imaging until progressive disease (PD).

Protective Effects of the Food Supplement Flexovital in a Model of Cardiovascular-Kidney-Metabolic Syndrome in Mice.

The prevalence of cardiovascular-kidney-metabolic (CKM) syndrome is increasing rapidly, and cardiovascular complications pose significant risks in individuals with kidney disease and metabolic dysfunction. Understanding the mechanisms of CKM disorders is crucial, as is the discovery of novel preventive treatments. This study aimed to examine the therapeutic effects of a specially formulated nitric oxide-enhancing food additive in a mouse model of CKM syndrome induced by unilateral nephrectomy (UNX) in combination with chronic Western diet (WD) feeding.

Decreased Adipose Lipid Turnover Associates With Cardiometabolic Risk and the Metabolic Syndrome.

Background: Disturbed white adipose tissue function is important for cardiometabolic risk and metabolic syndrome (MetS). Whether this involves adipose lipid turnover (lipolysis and synthesis of triglycerides) is unknown and was presently investigated in subcutaneous adipose tissue, the body's largest fat depot.

Methods: In cross-sectional studies in 78 subjects, adipose lipid age, representing overall lipid turnover (mobilization and storage), and lipid storage capacity were assessed by the incorporation of atmospheric C into adipose lipids.

Longitudinal changes in regional fat and muscle composition and cardiometabolic biomarkers over 5 years of hormone therapy in transgender individuals.

Background: Longitudinal studies investigating hormone therapy in transgender individuals are rare and often limited to 1- to 2-year follow-up periods.

Objectives And Methods: We examined changes in body composition, muscle volumes, and fat distribution as well as muscle strength, arterial stiffness, and cardiometabolic biomarkers in both transgender men (TM; n = 17, age 25 ± 5 years) and transgender women (TW; n = 16, age 28 ± 5 years) at baseline and after 1 and 5-6 years of hormone therapy in a longitudinal prospective cohort design. Whole-body and regional fat and muscle volumes were analyzed using magnetic resonance imaging, and blood samples were taken.

Personalized circulating tumor DNA analysis for sensitive disease monitoring and detection of relapse in neuroblastoma.

Circulating tumor DNA (ctDNA) has shown potential as a non-invasive tumor biomarker in neuroblastoma. Previous studies used generic assays for detection of selected predefined oncogenic variants as markers of ctDNA, which limits the sensitivity and excludes a subset of patients from analysis. Here we assessed patient-specific ctDNA analysis for treatment evaluation and detection of relapse in neuroblastoma.

Completion and reporting of COVID-19 clinical trials registered on ClinicalTrials.gov during the first 6 months of the pandemic: cohort study.

Background: Early in the COVID-19 pandemic, numerous clinical trials were initiated. Although concerns were raised regarding the quality of the trials, the eventual research output yielded from the trials remains unknown. The objective of this study was to include all clinical trials registered on ClinicalTrials.

The strength of interspecies interaction in a microbial community determines its susceptibility to invasion.

Previous work shows that a host's resident microbial community can provide resistance against an invading pathogen. However, this community is continuously changing over time due to adaptive mutations, and how these changes affect the invasion resistance of these communities remains poorly understood. To address this knowledge gap, we used an experimental evolution approach in synthetic communities of Escherichia coli and Salmonella Typhimurium to investigate how the invasion resistance of this community against a bacterium expressing a virulent phenotype, i.

Cardiometabolic risk assessment in transgender individuals - differential impact of sex hormones and sex chromosomes.

Background: While transgender individuals represent a significant group seeking medical care, the differential effect of sex on cardiometabolic risk metrics is incompletely understood. Therefore, the current study aimed to characterize the impact of sex hormones and chromosomes on a contemporary panel of cardiometabolic risk biomarkers and functional cardiovascular measurements.

Methods: 17 transmen and 17 transwomen were studied at baseline (T0), 4 weeks (hormonal castration, T1), and 11 months following gender-affirming hormone treatment (T12).

A novel model of cardiovascular-kidney-metabolic syndrome combining unilateral nephrectomy and high-salt-sugar-fat diet in mice.

The aim of this study was to explore biological interaction and pathophysiology mechanisms in a new mouse model of cardiovascular-kidney-metabolic (CKM) syndrome, induced by chronic moderate renal failure in combination with consumption of a customized Western diet rich in carbohydrates, fat and salt. Male C57BL/6J mice were subjected to unilateral nephrectomy, fed a customized Western diet rich not only in sugar and fat but also in salt, and followed for 12 weeks or 20 weeks. Sham-operated mice on a standard chow served as healthy controls.

Choice of alcohol over a natural reward: an experimental study in light and heavy social drinkers.

Rationale & Objectives: A core symptom of alcohol use disorder (AUD) is a progressively increased choice of alcohol over alternative rewards despite negative consequences. Here, we investigated choice between personalized alcohol vs. natural rewards in a laboratory setting, and compared this behavior between non-treatment-seeking heavy drinkers and light social drinkers.

A light-efficient and versatile multiplexing method for snapshot spectral imaging.

The study of rapid and stochastic events that involve multiple species, such as chemical reactions and plasma dynamics, requires means to capture multispectral information in two dimensions at both high temporal- and spatial resolution. Commercially available cameras that provide high temporal resolution are based on either signal intensification or rapid data acquisition. Intensified cameras provide extremely short acquisition times using intensification by means of micro channel plates, but the conversion between electrons and photons makes these cameras inherently monochrome.

Withdrawing versus Withholding Treatments in Medical Reimbursement Decisions: A Study on Public Attitudes.

Background: The use of policies in medical treatment reimbursement decisions, in which only future patients are affected, prompts a moral dilemma: is there an ethical difference between withdrawing and withholding treatment?

Design: Through a preregistered behavioral experiment involving 1,067 participants, we tested variations in public attitudes concerning withdrawing and withholding treatments at both the bedside and policy levels.

Results: In line with our first hypothesis, participants were more supportive of rationing decisions presented as withholding treatments compared with withdrawing treatments. Contrary to our second prestated hypothesis, participants were more supportive of decisions to withdraw treatment made at the bedside level compared with similar decisions made at the policy level.

Quantifying combined effects of colistin and ciprofloxacin against Escherichia coli in an in silico pharmacokinetic-pharmacodynamic model.

Co-administering a low dose of colistin (CST) with ciprofloxacin (CIP) may improve the antibacterial effect against resistant Escherichia coli, offering an acceptable benefit-risk balance. This study aimed to quantify the interaction between ciprofloxacin and colistin in an in silico pharmacokinetic-pharmacodynamic model from in vitro static time-kill experiments (using strains with minimum inhibitory concentrations, MIC 0.023-1 mg/L and MIC 0.

Suppression of the conditionally lethal phenotype by different compensatory mutations.

RNase P is an essential enzyme found across all domains of life that is responsible for the 5'-end maturation of precursor tRNAs. For decades, numerous studies have sought to elucidate the mechanisms and biochemistry governing RNase P function. However, much remains unknown about the regulation of RNase P expression, the turnover and degradation of the enzyme, and the mechanisms underlying the phenotypes and complementation of specific RNase P mutations, especially in the model bacterium, In , the temperature-sensitive (ts) mutation in the protein subunit of RNase P has arguably been one of the most well-studied mutations for examining the enzyme's activity in vivo.

Plutonium oxide melt structure and covalency.

Advances in nuclear power reactors include the use of mixed oxide fuel, containing uranium and plutonium oxides. The high-temperature behaviour and structure of PuO above 1,800 K remain largely unexplored, and these conditions must be considered for reactor design and planning for the mitigation of severe accidents. Here, we measure the atomic structure of PuO through the melting transition up to 3,000 ± 50 K using X-ray scattering of aerodynamically levitated and laser-beam-heated samples, with O/Pu ranging from 1.

Treatment Monitoring of a Patient with Synchronous Metastatic Angiosarcoma and Breast Cancer Using ctDNA.

Angiosarcoma is a rare and aggressive type of soft-tissue sarcoma with high propensity to metastasize. For patients with metastatic angiosarcoma, prognosis is dismal and treatment options are limited. To improve the outcomes, identifying patients with poor treatment response at an earlier stage is imperative, enabling alternative therapy.

Heteroresistance to piperacillin/tazobactam in is mediated by increased copy number of multiple β-lactamase genes.

Background: Piperacillin/tazobactam is a β-lactam/β-lactamase inhibitor combination with a broad spectrum of activity that is often used as empirical and/or targeted therapy among hospitalized patients. Heteroresistance (HR) is a form of antibiotic resistance in which a minority population of resistant cells coexists with a majority susceptible population that has been found to be a cause of antibiotic treatment failure in murine models.

Objectives: To determine the prevalence of HR and mechanisms of HR to piperacillin/tazobactam among bloodstream infection (BSI) isolates.