Serum drug levels and medication adherence in heart failure: A comparative cohort analysis.

Objective: To determine changes in medication adherence in two cohorts of heart failure patients differing by year of data collection and using a direct method of adherence detection - serum drug level testing.

Methods: We added a second cohort of patients to a prospective monocentric registry of chronic heart failure patients (LEVEL-CHF registry). The two cohorts share the same inclusion criteria but differ by the year of enrolment (2018 and 2020).

Identification of a novel Azaspirooxindolinone-based PROTAC for selective BTK degradation and enhanced anticancer activity.

Bruton's Tyrosine Kinase (BTK) is a key driver of hematological malignancies, autoimmune disorders, and neuroinflammation, making it an attractive therapeutic target. Proteolysis targeting chimeras (PROTACs) offer a novel strategy for BTK degradation via the E3 ubiquitin ligase pathway. Here, we evaluated nine azaspirooxindolinone-based PROTAC derivatives for their cytotoxicity and BTK-targeting activity.

Design, synthesis, and biological evaluation of novel azaspirooxindolinone derivatives as potent inhibitors of ITK and BTK-dependent cancers.

Interleukin-2-inducible T-cell kinase (ITK) and Bruton's tyrosine kinase (BTK) are two important members of the Tec family with crucial roles in immune system function. Deregulation in ITK and BTK activity is linked to several hematological malignancies, making them key targets for cancer immunotherapy. In this study, we synthesized a series of azaspirooxindolinone derivatives and evaluated their cytotoxic activity against ITK/BTK-negative and positive cancer cell lines, followed by enzymatic inhibition studies to assess the ITK/BTK kinase selectivity of two hit compounds.

MInfer: Bridging MetaboAnalyst and Jacobian analysis for metabolomic networks.

Background And Objective: Metabolomic interaction networks provide critical insights into the dynamic relationships between metabolites and their regulatory mechanisms. This study introduces MInfer, a novel computational framework that integrates outputs from MetaboAnalyst, a widely used metabolomic analysis tool, with Jacobian analysis to enhance the derivation and interpretation of these networks.

Methods: MInfer combines the comprehensive data processing capabilities of MetaboAnalyst with the mathematical modeling power of Jacobian analysis.

The burden of multimorbidity in patients with systemic lupus erythematosus - single-centre analysis.

Aims: Multimorbidity is a growing problem in the general population as well as in patients with rheumatic diseases like systemic lupus erythematosus (SLE). However, patients with SLE have twice the risk of developing multimorbidity than non-SLE patients. The aim of this study was to determine the prevalence of multimorbidity in patients with SLE treated in a university hospital.

Contemporary review of prognostic markers of prostate cancer from a pathologist perspective.

Prostate cancer is the most frequently diagnosed malignant tumour in men worldwide. To treat this condition, prognostic markers to distinguish indolent from aggressive disease, and biomarkers for metastatic forms are needed. From a pathologist's perspective, despite the plethora of emerging biomarkers, none to date has made its way into clinical practice.

Trends in Microbiology 2024.

Microbiology is a key component of modern science, significantly influencing various fields, such as agriculture, medicine, and environmental management, particularly through the One Health approach, which recognizes the interconnectedness of human, animal, and environmental health [...

The kinetics of uracil-N-glycosylase distribution inside replication foci.

Mismatched nucleobase uracil is commonly repaired through the base excision repair initiated by DNA uracil glycosylases. The data presented in this study strongly indicate that the nuclear uracil-N-glycosylase activity and nuclear protein content in human cell lines is highest in the S phase of the cell cycle and that its distribution kinetics partially reflect the DNA replication activity in replication foci. In this respect, the data demonstrate structural changes of the replication focus related to the uracil-N-glycosylase distribution several dozens of minutes before end of its replication.

Gait characteristics in idiopathic normal pressure hydrocephalus: a review on the effects of CSF tap test and shunt surgery.

Background: Idiopathic normal pressure hydrocephalus (iNPH) is a progressive disease characterized by disproportionate ventricular enlargement at brain imaging with gait disturbance and an increased risk of falling. Gait assessment is a key feature in the diagnosis of iNPH and characterization of post-surgical outcomes.

Research Question: How do gait parameters change 24 h after CSF tap test (CSFTT) and after ventriculoperitoneal shunt surgery?

Methods: The PRISMA guidelines were used to perform the systematic review.

Impact of antiphospholipid syndrome on placenta and uterine NK cell function: insights from a mouse model.

Antiphospholipid syndrome (APS) is associated with recurrent pregnancy morbidity, yet the underlying mechanisms remain elusive. We performed multifaceted characterization of the biological and transcriptomic signatures of mouse placenta and uterine natural killer (uNK) cells in APS. Histological analysis of APS placentas unveiled placental abnormalities, including disturbed angiogenesis, occasional necrotic areas, fibrin deposition, and nucleated red blood cell enrichment.

Triterpenoid phthalimides as selective anti-cancer agents targeting mitochondrial apoptosis.

Starting from benzyl 30-oxobetulinate and 30-oxobetulin diacetate, substituted dienes were synthesized and subjected to Diels-Alder reaction, yielding a variety of triterpenoid phthalates, phthalimides, and related derivatives. A total of 55 new compounds were prepared and tested for in vitro cytotoxic activity against eight cancer cell lines and two non-cancerous cell lines. Four compounds with IC values of 5 μM or lower were selected for further investigation.

Impact of the International Tumor Budding Consensus Conference Recommendations in Oral Cancer.

Objectives: Tumor budding was suggested as a valuable prognostic factor in oral squamous cell carcinoma (OSCC) but lacks a standardized scoring system. This study evaluates tumor budding in OSCC using the scoring system recommended by the International Tumor Budding Consensus Conference (ITBCC) 2016.

Materials And Methods: The study included 114 patients with resected OSCC.

Evaluation of corticoresistance in patients with thyroid eye disease and use of rituximab as a second-line treatment.

Purpose: High-dose intravenous glucocorticoids are the standard first-line treatment in active, moderate to severe and severe thyroid eye disease (TED). We evaluate the usefulness of clinical activity score (CAS) and thyroid-stimulating immunoglobulin (TSI) as predictors and/or post-treatment markers of corticoresistance in patients with TED and the effect of rituximab in second-line treatment.

Methods: We enrolled 236 patients with an active TED into this retrospective single-tertiary-center cohort study.

Real-world effectiveness of cladribine as an escalation strategy for MS: Insights from the Czech nationwide ReMuS registry.

Background: Cladribine, a selective immune reconstitution therapy, is approved for the treatment of adult patients with highly active multiple sclerosis (MS).

Objectives: Provide experience with cladribine therapy in a real-world setting.

Methods: This is a registry-based retrospective observational cohort study.

Unfolded protein response markers Grp78 and eIF2alpha are upregulated with increasing alpha-synuclein levels in Lewy body disease.

Aims: Endoplasmic reticulum stress followed by the unfolded protein response is one of the cellular mechanisms contributing to the progression of α-synuclein pathology in Parkinson's disease and other Lewy body diseases. We aimed to investigate the activation of endoplasmic reticulum stress and its correlation with α-synuclein pathology in human post-mortem brain tissue.

Methods: We analysed brain tissue from 45 subjects-14 symptomatic patients with Lewy body disease, 19 subjects with incidental Lewy body disease, and 12 healthy controls.

Impact of prior oral anticoagulation on admission stroke severity in patients with atrial fibrillation.

Background And Aims: In patients with atrial fibrillation, oral anticoagulation therapy is indicated for both primary and secondary prevention of stroke/systemic embolism. Though direct oral anticoagulants with greater safety and efficacy than warfarin were introduced into clinical practice at the beginning of the last decade, even now not all patients with AF have adequate preventative anticoagulant treatment. The primary goal of this study was to evaluate the impact of prior use of oral anticoagulants on admission stroke severity in those with AF.

Predictors of symptomatic intracerebral hemorrhage after endovascular treatment for acute ischemic stroke due to tandem lesion in anterior circulation.

Background: Endovascular treatment (EVT) of tandem lesion (TL) in the anterior circulation acute ischemic stroke (IS) usually requires periprocedural antithrombotic treatment and early initiation of dual antiplatelet therapy (DAPT) after carotid stenting. However, it may contribute to an occurrence of symptomatic intracerebral hemorrhage (SICH) in some cases. We investigated factors influencing the SICH occurrence and assessed the possible predictors of SICH after EVT.