Comparative study of ergosterol and 7-dehydrocholesterol and their endoperoxides: Generation, identification, and impact in phospholipid membranes and melanoma cells.

Melanoma is an aggressive cancer that has attracted attention in recent years due to its high mortality rate of 80%. Damage caused by oxidative stress generated by radical (type I reaction) and singlet oxygen, O (type II reaction) oxidative reactions may induce cancer. Thus, studies that aim to unveil the mechanism that drives these oxidative damage processes become relevant.

Healing Effect of in Burn Injuries.

Background: Burn injury is still the leading cause of mortality and morbidity in burn patients. We comapred healing effect of , silver sulfadiazine and alpha ointments on burn injuries in rat model.

Methods: Sixty female Sprague-Dawley rats in an animal experimental study were randomly divided to 5 equal groups as , silver sulfadiazine and (SSD), alpha, gel base and the burn injury left untreated.

Automated live-cell single-molecule tracking in enteroid monolayers reveals transcription factor dynamics probing lineage-determining function.

Lineage transcription factors (TFs) provide one regulatory level of differentiation crucial for the generation and maintenance of healthy tissues. To probe TF function by measuring their dynamics during adult intestinal homeostasis, we established HILO-illumination-based live-cell single-molecule tracking (SMT) in mouse small intestinal enteroid monolayers recapitulating tissue differentiation hierarchies in vitro. To increase the throughput, capture cellular features, and correlate morphological characteristics with diffusion parameters, we developed an automated imaging and analysis pipeline, broadly applicable to two-dimensional culture systems.

Colocalization of Cancer-Associated Biomarkers on Single Extracellular Vesicles for Early Detection of Cancer.

Detection of cancer early, when it is most treatable, remains a significant challenge because of the lack of diagnostic methods sufficiently sensitive to detect nascent tumors. Early-stage tumors are small relative to their tissue of origin, heterogeneous, and infrequently manifest in clinical symptoms. The detection of early-stage tumors is challenging given the lack of tumor-specific indicators (ie, protein biomarkers, circulating tumor DNA) to enable detection using a noninvasive diagnostic assay.

Bioengineered larynx and vocal folds: where are we today? A review.

The larynx is responsible for breathing, producing sound, and protecting the trachea against food aspiration through the cough reflex. Nowadays, scaffolding surgery has made it easier to regenerate damaged tissues by facilitating the influx of cells and growth factors. This review provides a comprehensive overview of the current knowledge on tissue engineering of the larynx and vocal folds.

Precise immunofluorescence canceling for highly multiplexed imaging to capture specific cell states.

Cell states are regulated by the response of signaling pathways to receptor ligand-binding and intercellular interactions. High-resolution imaging has been attempted to explore the dynamics of these processes and, recently, multiplexed imaging has profiled cell states by achieving a comprehensive acquisition of spatial protein information from cells. However, the specificity of antibodies is still compromised when visualizing activated signals.

Advanced feedback enhances sensorimotor adaptation.

It is widely recognized that sensorimotor adaptation is facilitated when feedback is provided throughout the movement compared with when it is provided at the end of the movement. However, the source of this advantage is unclear: continuous feedback is more ecological, dynamic, and available earlier than endpoint feedback. Here, we assess the relative merits of these factors using a method that allows us to manipulate feedback timing independent of actual hand position.

Dynamic noise estimation: A generalized method for modeling noise fluctuations in decision-making.

Computational cognitive modeling is an important tool for understanding the processes supporting human and animal decision-making. Choice data in decision-making tasks are inherently noisy, and separating noise from signal can improve the quality of computational modeling. Common approaches to model decision noise often assume constant levels of noise or exploration throughout learning (e.

Machine learning analyses identify multi-modal frailty factors that selectively discriminate four cohorts in the Alzheimer's disease spectrum: a COMPASS-ND study.

Background: Frailty indicators can operate in dynamic amalgamations of disease conditions, clinical symptoms, biomarkers, medical signals, cognitive characteristics, and even health beliefs and practices. This study is the first to evaluate which, among these multiple frailty-related indicators, are important and differential predictors of clinical cohorts that represent progression along an Alzheimer's disease (AD) spectrum. We applied machine-learning technology to such indicators in order to identify the leading predictors of three AD spectrum cohorts; viz.

The effect of topical magnesium on healing of pre-clinical burn wounds.

Background: Magnesium (Mg) is an essential factor in the healing process. This study aimed to evaluate the effect of Mg creams on healing burn wounds in the rat model.

Methods: To induce burns under general anaesthesia, a 2 × 2 cm2, 100 °C plate was placed for 12 s between the scapulas in 100 male adult Sprague Dawley rats.

Toward precision brain health: accurate prediction of a cognitive index trajectory using neuroimaging metrics.

The goal of precision brain health is to accurately predict individuals' longitudinal patterns of brain change. We trained a machine learning model to predict changes in a cognitive index of brain health from neurophysiologic metrics. A total of 48 participants (ages 21-65) completed a sensorimotor task during 2 functional magnetic resonance imaging sessions 6 mo apart.

A novel pathogenic mutation of MeCP2 impairs chromatin association independent of protein levels.

Loss-of-function mutations in cause Rett syndrome (RTT), a severe neurological disorder that mainly affects girls. Mutations in do occur in males occasionally and typically cause severe encephalopathy and premature lethality. Recently, we identified a missense mutation (c.

Double-Strand Break Repair Pathways Differentially Affect Processing and Transduction by Dual AAV Vectors.

Recombinant adeno-associated viral vectors (rAAV) are a powerful tool for gene delivery but have a limited DNA carrying capacity. Efforts to expand this genetic payload have focused on engineering the vector components, such as dual trans-splicing vectors which double the delivery size by exploiting the natural concatenation of rAAV genomes in host nuclei. We hypothesized that inefficient dual vector transduction could be improved by modulating host factors which affect concatenation.

Current Methods for Hyperpolarized [1-C]pyruvate MRI Human Studies.

MRI with hyperpolarized (HP) C agents, also known as HP C MRI, can measure processes such as localized metabolism that is altered in numerous cancers, liver, heart, kidney diseases, and more. It has been translated into human studies during the past 10 years, with recent rapid growth in studies largely based on increasing availability of hyperpolarized agent preparation methods suitable for use in humans. This paper aims to capture the current successful practices for HP MRI human studies with [1-C]pyruvate - by far the most commonly used agent, which sits at a key metabolic junction in glycolysis.

Predicting 30-day risk from benzodiazepine/Z-drug dispensations in older adults using administrative data: A prognostic machine learning approach.

Objective: To develop a machine-learning (ML) model using administrative data to estimate risk of adverse outcomes within 30-days of a benzodiazepine (BZRA) dispensation in older adults for use by health departments/regulators.

Design, Setting And Participants: This study was conducted in Alberta, Canada during 2018-2019 in Albertans 65 years of age and older. Those with any history of malignancy or palliative care were excluded.

RNA polymerase II depletion from the inactive X chromosome territory is not mediated by physical compartmentalization.

Subnuclear compartmentalization has been proposed to play an important role in gene regulation by segregating active and inactive parts of the genome in distinct physical and biochemical environments. During X chromosome inactivation (XCI), the noncoding Xist RNA coats the X chromosome, triggers gene silencing and forms a dense body of heterochromatin from which the transcription machinery appears to be excluded. Phase separation has been proposed to be involved in XCI, and might explain the exclusion of the transcription machinery by preventing its diffusion into the Xist-coated territory.

Cell Proliferation, Viability, Differentiation, and Apoptosis of Iron Oxide Labeled Stem Cells Transfected with Lipofectamine Assessed by MRI.

To assess in vitro and in vivo tracking of iron oxide labeled stem cells transfected by lipofectamine using magnetic resonance imaging (MRI), rat dental pulp stem cells (DPSCs) were characterized, labeled with iron oxide nanoparticles, and then transfected with lipofectamine to facilitate the internalization of these nanoparticles. Cell proliferation, viability, differentiation, and apoptosis were investigated. Prussian blue staining and MRI were used to trace transfected labeled cells.

Single-molecule tracking (SMT): a window into live-cell transcription biochemistry.

How molecules interact governs how they move. Single-molecule tracking (SMT) thus provides a unique window into the dynamic interactions of biomolecules within live cells. Using transcription regulation as a case study, we describe how SMT works, what it can tell us about molecular biology, and how it has changed our perspective on the inner workings of the nucleus.

Transcription factor SOX15 regulates stem cell pluripotency and promotes neural fate during differentiation by activating the neurogenic gene Hes5.

SOX2 and SOX15 are Sox family transcription factors enriched in embryonic stem cells (ESCs). The role of SOX2 in activating gene expression programs essential for stem cell self-renewal and acquisition of pluripotency during somatic cell reprogramming is well-documented. However, the contribution of SOX15 to these processes is unclear and often presumed redundant with SOX2 largely because overexpression of SOX15 can partially restore self-renewal in SOX2-deficient ESCs.

Radiotherapy Fraction in Limited-Stage Small Cell Lung Cancer in the Modern Era: A Systematic Review and Meta-Analysis of 8006 Reconstructed Individual Patient Data.

The optimal thoracic radiotherapy (TRT) dose and fractionation for limited-stage small cell lung cancer (LS-SCLC) using modern techniques remain unclear. We conducted systematic review and meta-analyses of the efficacy and safety differences between definitive hypofractionated TRT (HypoTRT), conventional TRT (ConvTRT) and hyperfractionated TRT (HyperTRT), especially in the modern era. Eligible randomized controlled trials (RCTs), real-world cohorts, and single-arm trials published between 1990 and 2021 were identified.

Development and Validation of a Machine Learning Model to Estimate Risk of Adverse Outcomes Within 30 Days of Opioid Dispensation.

Importance: Machine learning approaches can assist opioid stewardship by identifying high-risk opioid prescribing for potential interventions.

Objective: To develop a machine learning model for deployment that can estimate the risk of adverse outcomes within 30 days of an opioid dispensation as a potential component of prescription drug monitoring programs using access to real-world data.

Design, Setting, And Participants: This prognostic study used population-level administrative health data to construct a machine learning model.

Enhancer-promoter interactions and transcription are largely maintained upon acute loss of CTCF, cohesin, WAPL or YY1.

It remains unclear why acute depletion of CTCF (CCCTC-binding factor) and cohesin only marginally affects expression of most genes despite substantially perturbing three-dimensional (3D) genome folding at the level of domains and structural loops. To address this conundrum, we used high-resolution Micro-C and nascent transcript profiling in mouse embryonic stem cells. We find that enhancer-promoter (E-P) interactions are largely insensitive to acute (3-h) depletion of CTCF, cohesin or WAPL.