Development and Discovery of a Selective Degrader of Casein Kinases 1 δ/ε.

Members of the casein kinase 1 (CK1) family have emerged as key regulators of cellular signaling and as potential drug targets. Functional annotation of the 7 human isoforms would benefit from isoform-selective inhibitors, allowing studies on the role of these enzymes in normal physiology and disease pathogenesis. However, due to significant sequence homology within the catalytic domain, isoform selectivity is difficult to achieve with conventional small molecules.

Identification of Compounds Contributing to Glucocorticoid Activity in Indoor Dust Supported by Orthogonal Fractionation.

Indoor dust contains various endocrine-disrupting contaminants, yet the effect drivers of observed glucocorticoid activity are completely unknown. This study conducted an effect-directed analysis using orthogonal fractionation to identify effect drivers of glucocorticoid activity in indoor dust. After the detection of bioactivity using a human cell line stably transfected with a reporter gene, the sample underwent parallel HPLC fractionations with octadecyl, pentafluorophenyl, and aminopropyl columns to obtain orthogonal fractions.

Pre-implantation Scalp EEG Can Predict VNS Efficacy in Children.

Vagal nerve stimulation (VNS) is a therapeutical option for the treatment of drug-resistant epileptic patients. The response to VNS varies from patient to patient and is difficult to predict. The proposed study is based on our previous work, identifying relative mean power in pre-implantation EEG as a reliable marker for VNS efficacy prediction in adult patients.

Persistent humid climate favored the Qin and Western Han Dynasties in China around 2,200 y ago.

The Qin and Western Han dynasties (221 BCE to 24 CE) represent an era of societal prosperity in China. However, due to a lack of high-resolution paleoclimate records it is still unclear whether the agricultural boost documented for this period was associated with more favorable climatic conditions. Here, multiparameter analysis of annually resolved tree-ring records and process-based physiological modeling provide evidence of stable and consistently humid climatic conditions during 270 to 77 BCE in northern China.

Respiratory Viruses in Patients With Hematological Malignancy in Boreal Autumn/Winter 2023-2024: EPICOVIDEHA-EPIFLUEHA Report.

Community-acquired respiratory viral infections (CARV) significantly impact patients with hematological malignancies (HM), leading to high morbidity and mortality. However, large-scale, real-world data on CARV in these patients is limited. This study analyzed data from the EPICOVIDEHA-EPIFLUEHA registry, focusing on patients with HM diagnosed with CARV during the 2023-2024 autumn-winter season.

Protocol: The impact of integrated thematic instruction model on primary and secondary school students compared to standard teaching: A protocol of systematic review.

This is the protocol for a Campbell systematic review. The objectives are as follows. This systematic review will examine the impact of the Integrated Thematic Instruction (ITI) on academic attainment and other possible outcomes of primary and secondary school students compared to standard teaching.

Estimating the energy of dissipative neural systems.

There is, at present, a lack of consensus regarding precisely what is meant by the term 'energy' across the sub-disciplines of neuroscience. Definitions range from deficits in the rate of glucose metabolism in consciousness research to regional changes in neuronal activity in cognitive neuroscience. In computational neuroscience virtually all models define the energy of neuronal regions as a quantity that is in a continual process of dissipation to its surroundings.

Vancomycin wound penetration in open-heart surgery patients receiving negative pressure wound therapy for deep sternal wound infection.

Introduction: It is hypothesized that systemically administered antibiotics penetrate wound sites more effectively during negative pressure wound therapy (NPWT). However, there is a lack of clinical data from patients who receive NPWT for deep sternal wound infection (DSWI) after open-heart surgery. Here, we evaluated vancomycin penetration into exudate in this patient group.

Effects of two different dexamethasone dosing regimens on ventilator-free days and long-term mortality in COVID-19 patients with moderate-to-severe ARDS: the REMED randomized clinical trial.

Background: Dexamethasone 6 mg in patients with severe COVID-19 has been shown to decrease mortality and morbidity. The effects of higher doses of corticosteroid, that would further increase anti-inflammatory effects, are uncertain. The objective of our study was to assess the effect of 20 mg dexamethasone vs.

Microbial enzymes as powerful natural anti-biofilm candidates.

Bacterial biofilms pose significant challenges, from healthcare-associated infections to biofouling in industrial systems, resulting in significant health impacts and financial losses globally. Classic antimicrobial methods often fail to eradicate sessile microbial communities within biofilms, requiring innovative approaches. This review explores the structure, formation, and role of biofilms, highlighting the critical importance of exopolysaccharides in biofilm stability and resistance mechanisms.

Survey on the current practice of research ethics committees in the Czech academic environment: a mixed-methods study.

Background: The primary objective of this study was to conduct a comprehensive questionnaire survey on the practices of research ethics committees reviewing academic research projects in Czechia. The study aims to provide an unbiased and objective assessment of the current practices of research ethics committees, namely to obtain the missing data on their functioning in the context of academic research, to identify difficulties and shortages that threaten the responsible functioning of research ethics committees in the country and to investigate the implementation of Additional Protocol on Biomedical Research CETS No. 195 in their practice.

Evaluating the need for standardised disease manifestation categories in patients infected with the tick-borne encephalitis virus: A Delphi panel.

Categorization systems for tick-borne encephalitis virus (TBEV) infection lack consistency in classifying disease severity. To evaluate the need for a standard, consensus-based categorisation system for TBEV infection across subtypes, we gathered an expert panel of clinicians and scientists with diverse expertise in TBEV infection. Consensus was sought using the Delphi technique, which consisted of 2 web-based survey questionnaires and a final, virtual, consensus-building exercise.

Are We Estimating the Mean and Variance Correctly in the Presence of Observations Outside of Measurable Range?

Laboratory measurements used for safety assessments in clinical trials are subject to the limits of the used laboratory equipment. These limits determine the range of values which the equipment can accurately measure. When observations fall outside the measurable range, this creates a problem in estimating parameters of the normal distribution.

Ring 18 chromosome associated with cleft palate: case report and comprehensive literature review of clinical symptoms.

Background: Ring 18 chromosome is a rare chromosomal aberration associated with a wide range of symptoms affecting all organ systems. One possible symptom associated with this condition is an orofacial cleft. However, to date, there are very few reported cases where the cleft has been surgically treated.

Myasthenia gravis: understanding treatment patterns and direct medical costs in the Czech Republic.

Background: Myasthenia gravis (MG) is a rare autoimmune disorder with significant clinical implications, including life-threatening myasthenic crises and exacerbations. Understanding real-world treatment patterns, especially associated direct medical costs, is essential for the effective management of healthcare delivery.

Methods: We conducted a descriptive cohort study using health administrative claims data from the Czech Republic covering more than 1,500 prevalent MG patients.

Using iVR to deliver optimal psychotherapy experience-current perspectives on VRET for acrophobia.

Immersive Virtual Reality (iVR) presents a promising avenue for treating acrophobia through Virtual Reality Exposure Therapy (VRET). This paper explores the current state of VRET for acrophobia, identifying significant technological and practical barriers that limit its effectiveness and hinder widespread adoption. Key challenges include the need for more advanced and realistic user experiences, and for the integration of biofeedback mechanisms.

The impact of 3-sulfo-taurolithocholic acid on ATPase activity in patients' colorectal cancer and normal colon tissues, and its hepatic effects in rodents.

Colorectal cancer is influenced by genetic mutations, lifestyle factors, and diet, particularly high fat intake, which raises bile acid levels in the intestinal lumen. This study hypothesized that bile acids contribute to tumorigenesis by disrupting ion transport and ATPase activity in the intestinal mucosa. The effects of 3-sulfo-taurolithocholic acid (TLC-S) on ATPase activity were investigated in colorectal cancer samples from 10 patients, using adjacent healthy tissue as controls, and in rodent liver function.

Exploring the dynamics of reactive oxygen species from CaviPlasma and their disinfection and degradation potential - the case of cyanobacteria and cyanotoxins.

We investigated the production of highly reactive oxygen species (ROS) in solutions undergoing treatment using CaviPlasma (CP) technology. This technology combines plasma discharge with hydrodynamic cavitation. This study focused on factors such as pH, conductivity, presence of salts and organic matter affecting ROS formation and their stability in solutions.

Degradable starch microspheres transarterial chemoembolization (DSM-TACE) in patients with unresectable hepatocellular carcinoma: results from the Prospective Multicenter Observational HepaStar Trial.

Objectives: Despite increasing interest, prospective data on the use of degradable starch microsphere-transarterial chemoembolization (DSM-TACE) in the management of patients with unresectable HCC are still scarce. The objective of the HepaStar study was to collect prospective safety and effectiveness data in a prospective multicenter observational study.

Materials And Methods: Between January 2017 and December 2022, consecutive participants with unresectable or recurrent HCC treated with DSM-TACE as standard of care at 6 participating centers in Europe were enrolled.

Full-length direct RNA sequencing uncovers stress granule-dependent RNA decay upon cellular stress.

Cells react to stress by triggering response pathways, leading to extensive alterations in the transcriptome to restore cellular homeostasis. The role of RNA metabolism in shaping the cellular response to stress is vital, yet the global changes in RNA stability under these conditions remain unclear. In this work, we employ direct RNA sequencing with nanopores, enhanced by 5' end adapter ligation, to comprehensively interrogate the human transcriptome at single-molecule and -nucleotide resolution.

Hyperglycemia-Driven Insulin Signaling Defects Promote Parkinson's Disease-like Pathology in Mice.

This study aims to determine the effect of chronic hyperglycemia, induced by a high-fat diet and STZ-induced diabetes, on the development of Parkinson's disease-like characteristics. Understanding this relationship is crucial in pharmacology, neurology, and diabetes, as it could potentially lead to developing new therapeutic strategies for Parkinson's disease. Our study employed a comprehensive approach to investigate the effect of hyperglycemia on Parkinson's disease-like characteristics.

Arthropod Food Webs in the Foreland of a Retreating Greenland Glacier: Integrating Molecular Gut Content Analysis With Structural Equation Modelling.

The Arctic has warmed nearly four times faster than the global average since 1979, resulting in rapid glacier retreat and exposing new glacier forelands. These forelands offer unique experimental settings to explore how global warming impacts ecosystems, particularly for highly climate-sensitive arthropods. Understanding these impacts can help anticipate future biodiversity and ecosystem changes under ongoing warming scenarios.