Navigating from cellular phenotypic screen to clinical candidate: selective targeting of the NLRP3 inflammasome.

The NLRP3 inflammasome plays a pivotal role in host defense and drives inflammation against microbial threats, crystals, and danger-associated molecular patterns (DAMPs). Dysregulation of NLRP3 activity is associated with various human diseases, making it an attractive therapeutic target. Patients with NLRP3 mutations suffer from Cryopyrin-Associated Periodic Syndrome (CAPS) emphasizing the clinical significance of modulating NLRP3.

A landscape of consciousness: Toward a taxonomy of explanations and implications.

Diverse explanations or theories of consciousness are arrayed on a roughly physicalist-to-nonphysicalist landscape of essences and mechanisms. Categories: Materialism Theories (philosophical, neurobiological, electromagnetic field, computational and informational, homeostatic and affective, embodied and enactive, relational, representational, language, phylogenetic evolution); Non-Reductive Physicalism; Quantum Theories; Integrated Information Theory; Panpsychisms; Monisms; Dualisms; Idealisms; Anomalous and Altered States Theories; Challenge Theories. There are many subcategories, especially for Materialism Theories.

A decade of change: The evolution of pharmacy services at U.S. cystic fibrosis centers.

Introduction: People with cystic fibrosis (pwCF) require a multidisciplinary care team due to disease complexity. The Cystic Fibrosis Foundation (CFF) notes that pharmacists are recommended, while other organizations consider pharmacists required. In 2016, the CFF initiated a grant program for CFF-accredited care centers and affiliate programs (CFF-ACCAP) to implement outpatient pharmacy services.

Assessment of long-term medication adherence with cystic fibrosis: An integrated approach.

Introduction: Cystic fibrosis (CF) is a genetic disorder that creates a multisystem pathology resulting in complex treatment regimens. In 2014, 43% of people with CF at an academic medical center experienced medication acquisition barriers. The creation of an integrated specialty pharmacy with an embedded CF team pharmacist was launched in 2016.

The UCSC Genome Browser database: 2024 update.

The UCSC Genome Browser (https://genome.ucsc.edu) is a web-based genomic visualization and analysis tool that serves data to over 7,000 distinct users per day worldwide.

GenArk: towards a million UCSC genome browsers.

Interactive graphical genome browsers are essential tools in genomics, but they do not contain all the recent genome assemblies. We create Genome Archive (GenArk) collection of UCSC Genome Browsers from NCBI assemblies. Built on our established track hub system, this enables fast visualization of annotations.

At-Home, Cell-Free Synthetic Biology Education Modules for Transcriptional Regulation and Environmental Water Quality Monitoring.

As the field of synthetic biology expands, the need to grow and train science, technology, engineering, and math (STEM) practitioners is essential. However, the lack of access to hands-on demonstrations has led to inequalities of opportunity and practice. In addition, there is a gap in providing content that enables students to make their own bioengineered systems.

GenArk: Towards a million UCSC Genome Browsers.

Interactive graphical genome browsers are essential tools for biologists working with DNA sequences. Although tens of thousands of new genome assemblies have become available over the last decade, accessibility is limited by the work involved in manually creating browsers and curating annotations. The results can push the limits of data storage infrastructure.

At-home, cell-free synthetic biology education modules for transcriptional regulation and environmental water quality monitoring.

As the field of synthetic biology expands, the need to grow and train science, technology, engineering, and math (STEM) practitioners is essential. However, the lack of access to hands-on demonstrations has led to inequalities of opportunity and practice. In addition, there is a gap in providing content that enables students to make their own bioengineered systems.

Development of a Near-Infrared Spectroscopy (NIRS)-Based Characterization Approach for Inherent Powder Blend Heterogeneity in Direct Compression Formulations.

With the advent of continuous direct compression (CDC) process, it becomes increasingly desirable to characterize inherent powder blend heterogeneity at a small batch scale for a robust and CDC-amenable formulation. To accomplish this goal, a near infrared spectroscopy (NIRS)-based characterization approach was developed and implemented on multiple direct compression (DC) blends in this study, with the intended purpose of complementing existing formulation development tools and enabling to build an early CMC data package for late-phased process analytical technology (PAT) method development. Three fumaric acid DC blends, designed to harbor varied degrees of inherent blend heterogeneity, were employed.

The UCSC Genome Browser database: 2023 update.

The UCSC Genome Browser (https://genome.ucsc.edu) is an omics data consolidator, graphical viewer, and general bioinformatics resource that continues to serve the community as it enters its 23rd year.

Retrospective review of vancomycin monitoring via trough only versus two-point estimated area under the curve in pediatric and adult patients with cystic fibrosis.

Objectives: The primary objective of this study was to compare the occurrence of acute kidney injury (AKI) in patients with cystic fibrosis (CF) receiving intravenous (IV) vancomycin monitored through single serum trough concentrations and two-point estimated area under the curve (AUC). Time to next exacerbation and return to baseline lung function were also assessed.

Methods: A retrospective review was conducted in patients of all ages with CF admitted to the University of Kentucky who received IV vancomycin between October 2015 and January 2021.

A Survey of Pandemic Impacts on Pharmacy Residency Applications, Interviews, and Selection Factors.

To assess the impact of the COVID-19 pandemic on pharmacy residency application/interview processes, match rate, and factors influencing match rankings at a single college of pharmacy In spring of 2020 and 2021, an anonymous survey of fourth-year pharmacy school (P4) residency applicants at one college of pharmacy was administered. Survey responses were compared to explore trends in showcase participation, number/type/geographic dispersion of applications submitted, interview invitations, grade point average (GPA), research experience, and match rate. A thematic analysis evaluated common factors influencing match rankings.

Variant interpretation: UCSC Genome Browser Recommended Track Sets.

The UCSC Genome Browser has been an important tool for genomics and clinical genetics since the sequence of the human genome was first released in 2000. As it has grown in scope to display more types of data it has also grown more complicated. The data, which are dispersed at many locations worldwide, are collected into one view on the Browser, where the graphical interface presents the data in one location.

Development of a Freeze-Dried CRISPR-Cas12 Sensor for Detecting in the Secondary Science Classroom.

Training the future synthetic biology workforce requires the opportunity for students to be exposed to biotechnology concepts and activities in secondary education. Detecting bacteria in arthropods using polymerase chain reaction (PCR) has become a common way for secondary students to investigate and apply recombinant DNA technology in the science classroom. Despite this important activity, cutting-edge biotechnologies such as clustered regularly interspaced short palindromic repeat (CRISPR)-based diagnostics have yet to be widely implemented in the classroom.

Optimization of Spray-Drying Parameters for Formulation Development at Preclinical Scale.

Spray-drying dispersion (SDD) is a well-established manufacturing technique used to prepare amorphous solid dispersions (ASDs), allowing for poorly soluble drugs to have improved bioavailability. However, the process of spray-drying with multiple factors and numerous variables can lead to a lengthy development timeline with intense resource requirements, which becomes the main obstacle limiting spray-drying development at the preclinical stage. The purpose of this work was to identify optimized preset parameters for spray-drying to support the early development of ASDs suitable for most circumstances rather than individual optimization.

The UCSC Genome Browser database: 2022 update.

The UCSC Genome Browser, https://genome.ucsc.edu, is a graphical viewer for exploring genome annotations.

Optimization of Vancomycin Dosing to Achieve Target Area Under the Curve in Pediatrics.

Objective: Vancomycin dosing requirements to achieve a target area under curve/minimum inhibitory concentration (AUC/MIC) of 400 to 600 mg•hr/L have not been established in pediatrics. Dose modeling studies and recent guidelines suggest dosing higher than historical recommendations. This study examines dosing requirements to achieve target AUC/MIC in human pediatric patients.

Impact of surfactant selection and incorporation on in situ nanoparticle formation from amorphous solid dispersions.

Spray dried amorphous solid dispersions (ASDs) stand as one of the most effective formulation strategies to address issues of low aqueous solubility when developing new chemical entities.An emerging research topic focusing on the formation of amorphous nanoparticles or nanodroplets from ASD formulations has attracted attention recently. These ASD nanoparticlescan be highly beneficial and able to further increase oral bioavailability.

Comparison of the predictive value of area under the curve versus maximum serum concentration of intravenous tobramycin in cystic fibrosis patients treated for an acute pulmonary exacerbation.

Objectives: The primary objective of this study was to compare the therapeutic predictive value of area under the curve (AUC ) versus maximum concentration (C ) in cystic fibrosis (CF) patients receiving intravenous (IV) tobramycin for a Pseudomonas aeruginosa (PsA) acute pulmonary exacerbation (APE). Acute kidney injury (AKI) incidence and the relationship between time undetectable and efficacy were also assessed.

Methods: A retrospective review was conducted in patients aged at least 1 month with a diagnosis of CF receiving IV tobramycin for treatment of a PsA APE and admitted to the University of Kentucky between August 2015 and August 2019.

The Role of Biologics in the Management of Asthma in the Pediatric Patient.

The management of pediatric patients with asthma continues to be a major health issue. For many patients, traditional therapies have been very effective, but for a large number of patients asthma remains poorly controlled. This leads to significant morbidity and impairment to quality of life.

CFTR modulator drug desensitization: Preserving the hope of long term improvement.

The development of modulator therapy has, for the first time, allowed direct targeting of the underlying cause of cystic fibrosis (CF), the cystic fibrosis transmembrane conductance regulator (CFTR). Patients treated with CFTR modulators have improvement in lung function and decreased rates of pulmonary exacerbations. In 2019, elexacaftor/tezacaftor/ivacaftor was approved for use in the United States, opening these therapies to 90% of patients with CF.

Discovery of a dual pathway aggregation mechanism for a therapeutic constrained peptide.

Constrained peptides (CPs) have emerged as attractive candidates for drug discovery and development. To fully unlock the therapeutic potential of CPs, it is crucial to understand their physical stability and minimize the formation of aggregates that could induce immune responses. Although amyloid like aggregates have been researched extensively, few studies have focused on aggregates from other peptide scaffolds (e.