Liquid biopsy of peripheral blood using mass spectrometry detects primary extramedullary disease in multiple myeloma patients.

Multiple myeloma (MM) is the second most prevalent hematological malignancy, characterized by infiltration of the bone marrow by malignant plasma cells. Extramedullary disease (EMD) represents a more aggressive condition involving the migration of a subclone of plasma cells to paraskeletal or extraskeletal sites. Liquid biopsies could improve and speed diagnosis, as they can better capture the disease heterogeneity while lowering patients' discomfort due to minimal invasiveness.

Single-cell profiling of surface glycosphingolipids opens a new dimension for deconvolution of breast cancer intratumoral heterogeneity and phenotypic plasticity.

Glycosylated sphingolipids (GSLs) are a diverse group of cellular lipids typically reported as being rare in normal mammary tissue. In breast cancer (BCa), GSLs have emerged as noteworthy markers associated with breast cancer stem cells, mediators of phenotypic plasticity, and contributors to cancer cell chemoresistance. GSLs are potential surface markers that can uniquely characterize the heterogeneity of the tumor microenvironment, including cancer cell subpopulations and epithelial-mesenchymal plasticity (EMP).

A computational workflow for analysis of missense mutations in precision oncology.

Every year, more than 19 million cancer cases are diagnosed, and this number continues to increase annually. Since standard treatment options have varying success rates for different types of cancer, understanding the biology of an individual's tumour becomes crucial, especially for cases that are difficult to treat. Personalised high-throughput profiling, using next-generation sequencing, allows for a comprehensive examination of biopsy specimens.

A genome-wide association meta-analysis of all-cause and vascular dementia.

Introduction: Dementia is a multifactorial disease with Alzheimer's disease (AD) and vascular dementia (VaD) pathologies making the largest contributions. Yet, most genome-wide association studies (GWAS) focus on AD.

Methods: We conducted a GWAS of all-cause dementia (ACD) and examined the genetic overlap with VaD.

Intercellular interaction between FAP+ fibroblasts and CD150+ inflammatory monocytes mediates fibrostenosis in Crohn's disease.

Crohn's disease (CD) is marked by recurring intestinal inflammation and tissue injury, often resulting in fibrostenosis and bowel obstruction, necessitating surgical intervention with high recurrence rates. To elucidate the mechanisms underlying fibrostenosis in CD, we analyzed the transcriptome of cells isolated from the transmural ileum of patients with CD, including a trio of lesions from each patient: non-affected, inflamed, and stenotic ileum samples, and compared them with samples from patients without CD. Our computational analysis revealed that profibrotic signals from a subset of monocyte-derived cells expressing CD150 induced a disease-specific fibroblast population, resulting in chronic inflammation and tissue fibrosis.

Fibrotic extracellular matrix impacts cardiomyocyte phenotype and function in an iPSC-derived isogenic model of cardiac fibrosis.

Cardiac fibrosis occurs following insults to the myocardium and is characterized by the abnormal accumulation of non-compliant extracellular matrix (ECM), which compromises cardiomyocyte contractile activity and eventually leads to heart failure. This phenomenon is driven by the activation of cardiac fibroblasts (cFbs) to myofibroblasts and results in changes in ECM biochemical, structural and mechanical properties. The lack of predictive in vitro models of heart fibrosis has so far hampered the search for innovative treatments, as most of the cellular-based in vitro reductionist models do not take into account the leading role of ECM cues in driving the progression of the pathology.

The role of N6-methyladenosine RNA methylation in the crosstalk of circadian clock and neuroinflammation in rodent suprachiasmatic nuclei.

N6-methyladenosine (mA) is the most abundant epitranscriptomic mark that regulates the fate of RNA molecules. Recent studies have revealed a bidirectional interaction between mA modification and the circadian clock. However, the precise temporal dynamics of mA global enrichment in the central circadian pacemaker have not been fully elucidated.

Long circulating liposomal platform utilizing hydrophilic polymer-based surface modification: preparation, characterisation, and biological evaluation.

Liposomes are one of the most important drug delivery vectors, nowadays used in clinics. In general, polyethylene glycol (PEG) is used to ensure the stealth properties of the liposomes. Here, we have employed hydrophilic, biocompatible and highly non-fouling N-(2-hydroxypropyl) methacrylamide (HPMA)-based copolymers containing hydrophobic cholesterol anchors for the surface modification of liposomes, which were prepared by the method of lipid film hydration and extrusion through 100 nm polycarbonate filters.

HIV-protease inhibitors potentiate the activity of carfilzomib in triple-negative breast cancer.

Background: Resistance to chemotherapy is a major problem in the treatment of patients with triple-negative breast cancer (TNBC). Preclinical data suggest that TNBC is dependent on proteasomes; however, clinical observations indicate that the efficacy of proteasome inhibitors in TNBC may be limited, suggesting the need for combination therapies.

Methods: We compared bortezomib and carfilzomib and their combinations with nelfinavir and lopinavir in TNBC cell lines and primary cells with regard to their cytotoxic activity, functional proteasome inhibition, and induction of the unfolded protein response (UPR).

GASP: A Pan-Specific Predictor of Family 1 Glycosyltransferase Acceptor Specificity Enabled by a Pipeline for Substrate Feature Generation and Large-Scale Experimental Screening.

Glycosylation represents a major chemical challenge; while it is one of the most common reactions in Nature, conventional chemistry struggles with stereochemistry, regioselectivity, and solubility issues. In contrast, family 1 glycosyltransferase (GT1) enzymes can glycosylate virtually any given nucleophilic group with perfect control over stereochemistry and regioselectivity. However, the appropriate catalyst for a given reaction needs to be identified among the tens of thousands of available sequences.

CoVAMPnet: Comparative Markov State Analysis for Studying Effects of Drug Candidates on Disordered Biomolecules.

Computational study of the effect of drug candidates on intrinsically disordered biomolecules is challenging due to their vast and complex conformational space. Here, we developed a comparative Markov state analysis (CoVAMPnet) framework to quantify changes in the conformational distribution and dynamics of a disordered biomolecule in the presence and absence of small organic drug candidate molecules. First, molecular dynamics trajectories are generated using enhanced sampling, in the presence and absence of small molecule drug candidates, and ensembles of soft Markov state models (MSMs) are learned for each system using unsupervised machine learning.

Social and environmental stressors of cardiometabolic health.

Exposures to social and environmental stressors arise individual behavioural response and thus indirectly affect cardiometabolic health. The aim of this study was to investigate several social and environmental stressors and the paths of their influence on cardiometabolic health. The data of 2154 participants (aged 25-64 years) from the cross-sectional population-based study were analysed.

C-methionine in the diagnostics and management of glioblastoma patients with rapid early progression: nonrandomized, open label, prospective clinical trial (GlioMET).

Background: Glioblastoma (GBM) is the most common and aggressive primary brain cancer. The treatment of GBM consists of a combination of surgery and subsequent oncological therapy, i.e.

Factors influencing the efficacy of recombinant tissue plasminogen activator: Implications for ischemic stroke treatment.

Intravenous thrombolysis with a recombinant tissue plasminogen activator (rt-PA) is the first-line treatment of acute ischemic stroke. However, successful recanalization is relatively low and the underlying processes are not completely understood. The goal was to provide insights into clinically important factors potentially limiting rt-PA efficacy such as clot size, rt-PA concentration, clot age and also rt-PA in combination with heparin anticoagulant.

Subpleural pulmonary nodule marking with patent blue V dye prior to surgical resection.

Background And Objective: Subpleural located pulmonary nodules are perioperatively invisible to the surgeon. Their precise identification is conventionally possible by palpation, but often at the cost of performing a thoracotomy. The aim of the study was to evaluate the success rate and feasibility of the pre-operative CT-guided marking subpleural localized nodule using a mixture of Patent Blue V and an iodine contrast agent prior to the extra-anatomical video-assisted thoracoscopic surgery (VATS) resection in patients for whom the primary anatomical resection in terms of segmentectomy or lobectomy was not indicated.

Rupture point is associated with divergent hemodynamics in intracranial aneurysms.

Background: Understanding the risk factors leading to intracranial aneurysm (IA) rupture have still not been fully clarified. They are vital for proper medical guidance of patients harboring unruptured IAs. Clarifying the hemodynamics associated with the point of rupture could help could provide useful information about some of the risk factors.

AggreProt: a web server for predicting and engineering aggregation prone regions in proteins.

Recombinant proteins play pivotal roles in numerous applications including industrial biocatalysts or therapeutics. Despite the recent progress in computational protein structure prediction, protein solubility and reduced aggregation propensity remain challenging attributes to design. Identification of aggregation-prone regions is essential for understanding misfolding diseases or designing efficient protein-based technologies, and as such has a great socio-economic impact.

Empagliflozin drives ferroptosis in anoikis-resistant cells by activating miR-128-3p dependent pathway and inhibiting CD98hc in breast cancer.

A tumour suppressor miRNA, miR-128-3p, is widely involved in various biological processes and has been found to get downregulated in breast cancer patients. We previously published that ectopically expressed miR-128-3p suppressed migration, invasion, cell cycle arrest, and breast cancer stem cells. In the present study, we explored the role of Empagliflozin (EMPA) as a miR-128-3p functionality-mimicking drug in inducing ferroptosis by inhibiting CD98hc.

Intact cell mass spectrometry coupled with machine learning reveals minute changes induced by single gene silencing.

Intact (whole) cell MALDI TOF mass spectrometry is a commonly used tool in clinical microbiology for several decades. Recently it was introduced to analysis of eukaryotic cells, including cancer and stem cells. Besides targeted metabolomic and proteomic applications, the intact cell MALDI TOF mass spectrometry provides a sufficient sensitivity and specificity to discriminate cell types, isogenous cell lines or even the metabolic states.

Clinical correlation between disease progression and central vein sign in pediatric onset multiple sclerosis: A binational study.

Background: The central vein sign (CVS) has been proposed as a novel MRI biomarker to improve diagnosis of pediatric-onset MS (POMS). However, the role of CVS in POMS progression has yet to be discovered.

Objectives: To investigate the appearance of CVS and its correlation with POMS disease progression.

Cascade of care for hypertension among apparently healthy and unhealthy individuals of 25-64 years in the Czech Republic.

Background: Despite accessible diagnostics and treatment of hypertension, a high proportion of patients worldwide remain unaware of their diagnosis, and even more remain untreated. Several studies suggest that absence of comorbidities is a predictive factor for unawareness and consequently non-treatment of hypertension. There are only a few studies that have assessed the hypertension prevalence and management among apparently healthy individuals.