Simultaneous Quantitation of Multiple Biological Thiols Using Reactive Ionization and Derivatization with Charged Mass Tags.

The biologically important thiols (cysteine, homocysteine, N-acetyl cysteine, and glutathione) are key species in redox homeostasis, and there is a clinical need to measure them rapidly, accurately, and simultaneously at low levels in complex biofluids. The solution to the challenge presented here is based on a new derivatizing reagent that combines a thiol-selective unit to optimize the chemical transformation and a precharged pyridinium unit chosen to maximize sensitivity in mass spectrometry. Derivatization is performed simultaneously with ionization ("reactive ionization"), and mass spectrometry is used to record and characterize the thiol reaction products.

Using human factors methods to mitigate bias in artificial intelligence-based clinical decision support.

Objectives: To highlight the often overlooked role of user interface (UI) design in mitigating bias in artificial intelligence (AI)-based clinical decision support (CDS).

Materials And Methods: This perspective paper discusses the interdependency between AI-based algorithm development and UI design and proposes strategies for increasing the safety and efficacy of CDS.

Results: The role of design in biasing user behavior is well documented in behavioral economics and other disciplines.

Point-of-Care Ultrasound Infrastructure.

Point-of-care ultrasound (POCUS) infrastructure is the underpinning of a well integrated POCUS program. In order to achieve its full potential and fully integrate into the health care system, a POCUS program requires a robust and resilient infrastructure. The essential components of POCUS infrastructure are hardware, software, and an informed, well-integrated governance structure.

Thrombopoietic agents enhance bone healing in mice, rats, and pigs.

Achieving bone union remains a significant clinical dilemma. The use of osteoinductive agents, specifically bone morphogenetic proteins (BMPs), has gained wide attention. However, multiple side effects, including increased incidence of cancer, have renewed interest in investigating alternatives that provide safer, yet effective bone regeneration.

Polycomb group protein Mel18 inhibits hematopoietic stem cell self-renewal through repressing the transcription of self-renewal and proliferation genes.

Polycomb group (PcG) proteins play important roles in hematopoietic stem cell (HSC) self-renewal. Mel18 and Bmi1 are homologs of the PCGF subunit within the Polycomb repressive complex 1 (PRC1). Bmi1 (PCGF4) enhances HSC self-renewal and promotes terminal differentiation.

Experience with Aposematic Defense Triggers Attack Bias in a Mantid Predator ().

Studies of predator psychology in aposematism have suggested important effects of signal detection through space and time on outcomes of attack behavior. Both the integration of aposematic signals from prey and experience state of the predator can have important effects on attack decisions. The universality of these effects however, especially as it applies to non-avian predators such as arthropods, remains poorly understood.

Impulsive Choices Emerge When the Anterior Cingulate Cortex Fails to Encode Deliberative Strategies.

Impulsive individuals excessively discount the value of delayed rewards, and this is thought to reflect deficits in brain regions critical for impulse control such as the anterior cingulate cortex (ACC). Delay discounting (DD) is an established measure of cognitive impulsivity, referring to the devaluation of rewards delayed in time. This study used male Wistar rats performing a DD task to test the hypothesis that neural activity states in ACC ensembles encode strategies that guide decision-making.

Projected epidemiological trends and burden of liver cancer by 2040 based on GBD, CI5plus, and WHO data.

Incidence of liver cancer as one of the most common cancers worldwide and become the significant contributor for the mortality among cancer patients. The disease burden, risk factors, and trends in incidence and mortality of liver cancer globally was described subsequently estimated the projections of liver cancer incidence or mortality by 2040. Data regarding age-standardized incidence and mortality rates for liver cancer was obtained from multiple databases, including GLOBOCAN 2020, CI5 volumes I-XI, WHO mortality database, and Global Burden of Disease (GBD)-2019.

Post-Intensive Care Syndrome Family.

Family members of patients admitted to intensive care units often experience psychological distress, including depression, anxiety, and trauma symptoms, known as post-intensive care syndrome-family (PICS-F), due to the stress from having a critically ill loved one and resultant caregiver burden. Awareness of this syndrome is needed, as are prevention and management strategies, to improve outcomes.

Creating a Culture of an Awake and Walking Intensive Care Unit: In-Hospital Strategies to Mitigate Post-Intensive Care Syndrome.

The ABCDEF bundle and Awake and Walking intensive care unit (ICU) approach aim to prevent the long-term consequences of critical illness (ie, post-intensive care syndrome) by promoting patient wakefulness, cognition, and mobility. Humanizing the ICU experience is the key, preserving patients' function and autonomy. Successful implementation requires cultivating an ICU culture focused on avoiding sedatives and initiating prompt mobilization, addressing organizational barriers through tailored strategies.

Synthesis and structure-activity relationship of boronic acid bioisosteres of combretastatin A-4 as anticancer agents.

The boronic acid group plays an important role in drug discovery. Following our discovery of a boronic acid analog of combretastatin A-4 (CA-4), a series of analogs featuring a boronic acid group on the C phenyl ring of CA-4 was synthesized and evaluated for cytotoxicity, as well as for their ability to inhibit tubulin polymerization, inhibit the binding of [H]colchicine to tubulin and cause depolymerization of cellular microtubules. Modifications on the C ring of CA-4, either eliminating the methoxy group or replacing the C phenyl ring with a pyridine ring, resulted in a reduced potency for inhibiting tubulin polymerization, colchicine binding and cytotoxic activities as compared to CA-4.

Exploring dysfunctional barrier phenotypes associated with glaucoma using a human pluripotent stem cell-based model of the neurovascular unit.

Glaucoma is a neurodegenerative disease that results in the degeneration of retinal ganglion cells (RGCs) and subsequent loss of vision. While RGCs are the primary cell type affected in glaucoma, neighboring cell types selectively modulate RGCs to maintain overall homeostasis. Among these neighboring cell types, astrocytes, microvascular endothelial cells (MVECs), and pericytes coordinate with neurons to form the neurovascular unit that provides a physical barrier to limit the passage of toxic materials from the blood into neural tissue.

Deciphering the tissue-specific functional effect of Alzheimer risk SNPs with deep genome annotation.

Alzheimer's disease (AD) is a highly heritable brain dementia, along with substantial failure of cognitive function. Large-scale genome-wide association studies (GWASs) have led to a set of SNPs significantly associated with AD and related traits. GWAS hits usually emerge as clusters where a lead SNP with the highest significance is surrounded by other less significant neighboring SNPs.

Single essential oils and their binary mixtures protect against ethanol-induced defects in a zebrafish fetal alcohol spectrum disorder model at the same level as folic acid.

This study evaluated protective effects of clove (SEO), thyme white (TEO), oregano (OEO), and caraway (CEO) essential oils (EOs), and their binary mixtures, in a zebrafish fetal alcohol spectrum disorder model. Furthermore, folic acid (FA) was used for comparison as it had previously shown protection against ethanol (EtOH)-induced defects. The co-exposure of zebrafish embryos to EtOH (150 mM) and FA (75 μM) or EOs and their binary mixtures (0.

Tissue-Safe Low-Temperature Plasma Treatment for Effective Management of Mature Peri-Implantitis Biofilms on Titanium Surfaces.

The unique screw-shape design and microstructure of implants pose a challenge for mechanical debridement in removing biofilms. Biofilms exhibit increased resistance to antimicrobials relative to single planktonic cells, emphasizing the need for effective biofilm removal during periodontal therapy for peri-implantitis treatment. To tackle this issue, our team evaluated the effectiveness of low-temperature plasma (LTP) for disinfecting titanium discs contaminated with multispecies biofilms associated with peri-implantitis, specifically focusing on biofilms matured for 14 and 21 days as well as biofilms that had formed on Straumann Ti-SLA implants for 21 days.

Splitting the chains: ultra-basal insulin analog uncovers a redox mechanism of hormone clearance.

Reporting in , Kjeldsen and colleagues describe a redox mechanism of insulin clearance based on separation of A- and B chains. Exploiting an ultra-long-acting analog protected from classical clearance pathways, the study highlights principles of protein stability in pharmacology.

Photo-responsive decellularized small intestine submucosa hydrogels.

Decellularized small intestine submucosa (dSIS) is a promising biomaterial for promoting tissue regeneration. Isolated from the submucosal layer of animal jejunum, SIS is rich in extracellular matrix (ECM) proteins, including collagen, laminin, and fibronectin. Following mild decellularization, dSIS becomes an acellular matrix that supports cell adhesion, proliferation, and differentiation.

Bone loss with aging is independent of gut microbiome in mice.

Emerging evidence suggests a significant role of gut microbiome in bone health. Aging is well recognized as a crucial factor influencing the gut microbiome. In this study, we investigated whether age-dependent microbial change contributes to age-related bone loss in CB6F1 mice.