StarPhase: Comprehensive Phase-Aware Pharmacogenomic Diplotyper for Long-Read Sequencing Data.

Pharmacogenomics is central to precision medicine, informing medication safety and efficacy. Pharmacogenomic diplotyping of complex genes requires full-length DNA sequences and detection of structural rearrangements. We introduce StarPhase, a tool that leverages PacBio HiFi sequence data to diplotype 21 CPIC Level A pharmacogenes and provides detailed haplotypes and supporting visualizations for , , and .

Bacterial clustering biomaterials as anti-infective therapies.

In Nature, bacterial clustering by host-released peptides or nucleic acids is an evolutionarily conserved immune defense strategy employed to prevent adhesion of pathogenic microbes, which is prerequisite for most infections. Synthetic anti-adhesion strategies present as non-lethal means of targeting bacteria and may potentially be used to avoid resistance against antimicrobial therapies. From bacteria-agglutinating biomolecules discovered in nature to synthetic designs involving peptides, cationic polymers and nanoparticles, the modes of actions appear broad and unconsolidated.

A modified and weighted Gower distance-based clustering analysis for mixed type data: a simulation and empirical analyses.

Background: Traditional clustering techniques are typically restricted to either continuous or categorical variables. However, most real-world clinical data are mixed type. This study aims to introduce a clustering technique specifically designed for datasets containing both continuous and categorical variables to offer better clustering compatibility, adaptability, and interpretability than other mixed type techniques.

Steps to Avoid Falls in the Elderly - a TECHnology Enhanced Intervention (SAFE-TECH) study: randomized controlled trial protocol for a community-based, multi-component fall prevention program.

Background: Falls and fall-related injuries among older adults in Singapore are a serious health problem that require early intervention. In previous research, exercise interventions have been effective in improving functional outcomes and reducing falls for a broad group of older adults. However, results from multi-domain, multi-component falls prevention programs for high fall risk older adults in the community remain equivocal.

Slc25a21 in cisplatin-induced acute kidney injury: a new target for renal tubular epithelial protection by regulating mitochondrial metabolic homeostasis.

Acute kidney injury (AKI) is a significant global health issue, which is often caused by cisplatin therapy and characterized by mitochondrial dysfunction. Restoring mitochondrial homeostasis in tubular cells could exert therapeutic effects. Here, we investigated Slc25a21, a mitochondrial carrier, as a potential target for AKI intervention.

Development and Usability of an Advance Care Planning Website (My Voice) to Empower Patients With Heart Failure and Their Caregivers: Mixed Methods Study.

Background: Web-based advance care planning (ACP) interventions offer a promising solution to improve ACP engagement, but none are specifically designed to meet the needs of patients with heart failure and their caregivers.

Objective: We aimed to develop and assess the usability and acceptability of a web-based ACP decision aid called "My Voice," which is tailored for patients with heart failure and their caregivers.

Methods: This study's team and advisory board codeveloped the content for both patient and caregiver modules in "My Voice.

mRNA vaccines encoding membrane-anchored RBDs of SARS-CoV-2 mutants induce strong humoral responses and can overcome immune imprinting.

We investigated mRNA vaccines encoding a membrane-anchored receptor-binding domain (RBD), each a fusion of a variant RBD, the transmembrane (TM) and cytoplasmic tail fragments of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. In naive mice, RBD-TM mRNA vaccines against SARS-CoV-2 variants induced strong humoral responses against the target RBD. Multiplex surrogate viral neutralization (sVNT) assays revealed broad neutralizing activity against a range of variant RBDs.

Examining the Association Between Overweight, Obesity, and Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis.

Background: Irritable bowel syndrome (IBS) is a common yet debilitating disorder of gut-brain interaction, characterized by gut-brain axis dysregulation, visceral hypersensitivity, and other comorbidities. Obesity has been hypothesized to be a risk factor linked to IBS, albeit evidence remains conflicting. Given the growing global prevalence of obesity and IBS, we performed a meta-analysis examining their purported association.

Towards Clinical Application: Calcium Waves for In Vitro Qualitative Assessment of Propagated Primary Human Corneal Endothelial Cells.

Corneal endothelium cells (CECs) regulate corneal hydration between the leaky barrier of the corneal endothelium and the ionic pumps on the surface of CECs. As CECs do not regenerate, loss of CECs leads to poor vision and corneal blindness. Corneal transplant is the only treatment option; however, there is a severe shortage of donor corneas globally.

Optimal adaptive SMART designs with binary outcomes.

In a sequential multiple-assignment randomized trial (SMART), a sequence of treatments is given to a patient over multiple stages. In each stage, randomization may be done to allocate patients to different treatment groups. Even though SMART designs are getting popular among clinical researchers, the methodologies for adaptive randomization at different stages of a SMART are few and not sophisticated enough to handle the complexity of optimal allocation of treatments at every stage of a trial.

Anti-inflammatory supramolecular hydrogel loaded chicoric acid based on graphene oxide modified hyaluronic acid and polyethylene glycol for rheumatoid arthritis treatment.

Chicoric acid (CA) as one of Chinese medicines had anti-inflammatory, less gastrointestinal irritation, less drug-resistance and low cost properties compared with chemical synthesized drug and biologics for rheumatoid arthritis (RA) treatment. To make CA preciously and effectly RA therapy, we firstly developed a supramolecular hydrogel (GHCAP) comprising β-cyclodextrin and graphene oxide (GO) modified hyaluronic acid (CD-HA-GO) as the "host" polymer and adamantane-modified four-arm polyethylene glycol (PEG-AD) as the "guest" polymer, and then the CA was loaded into the supramolecular hydrogel (DGHCAP). The results showed that DGHCAP exhibited injectable, high modulus, high CA loading rate (43.

Lipid-lowering drug and complement factor H genotyping-personalized treatment strategy for age-related macular degeneration.

We investigated whether the effect of lipid-lowering drugs (LLDs) on age-related macular degeneration (AMD) differs according to the main complement genetic variants in Singapore Epidemiology of Eye Diseases (SEED) ( = 5,579) and UK Biobank studies ( = 445,727). The effect of LLD was determined for each stratum of 20 complement genetic variants. In SEED, 484 individuals developed AMD and 216 showed progression over 6 years.

Fear and Impact of COVID-19 Among Post-Infected Adults: Types and Associations with Quality of Life and Post-Traumatic Stress Symptoms.

Survivors of COVID-19 are susceptible to diminished health-related quality of life (HRQoL) and adverse psychological health, which may be exacerbated by their experiences of fear and the impact of the pandemic itself. This study aims to identify distinct fear and impact patterns related to the COVID-19 pandemic among survivors through latent profile analysis (LPA) and examine the associations of fear and impact patterns with post-traumatic stress symptoms (PTSS) and HRQoL. A total of 5,890 Vietnamese COVID-19 survivors completed the COVID-19 Impact Battery- Disability Scale (CIB-D), the Fear of COVID-19 Scale (FCoV-19 S), the Impact of Event Scale-Revised for PTSS, and the 36-Item Short Form Survey (SF-36) for HRQoL.

Progress in the discovery and development of anticancer agents from marine cyanobacteria.

Covering 2010-April 2024There have been tremendous new discoveries and developments since 2010 in anticancer research based on marine cyanobacteria. Marine cyanobacteria are prolific sources of anticancer natural products, including the tubulin agents dolastatins 10 and 15 which were originally isolated from a mollusk that feeds on cyanobacteria. Decades of research have culminated in the approval of six antibody-drug conjugates (ADCs) and many ongoing clinical trials.

The interaction effects between summer heat exposure and economic development on the settlement intention in floating population in China.

Limited studies examined the interaction effects between summer heat exposure and economic development on the settlement intention, especially for the floating population. Binary logistic regression model was used to examine the association of summer temperature, per capita GRDP (PGRDP), summer temperature × PGRDP with settlement intention. Additive interaction term for summer temperature and PGRDP level was used to test the interactive effects.

Spatiotemporal evolution and transmission dynamics of Alpha and Delta SARS-CoV-2 variants contributing to sequential outbreaks in Cambodia during 2021.

Background: Tracking the emergence, introduction and spread of SARS-CoV-2 variants of concern are essential for informing public health strategies. In 2021, Cambodia faced two major epidemic waves of SARS-CoV-2 triggered by the successive rise of the Alpha and Delta variants.

Methods: Phylodynamic analysis of 1,163 complete SARS-CoV-2 genomes from Cambodia, along with global sequences, were conducted between February and September 2021 to infer viral introductions, molecular epidemiology and population dynamics.

Factors Associated with Chronic Chikungunya in Vitória, Espírito Santo State, Brazil, Between 2016 and 2020.

Chikungunya patients may develop chronic joint pain that can persist for months to years. This study aimed to determine the factors associated with Chikungunya chronicity. This case-control study involved data from patients with laboratory-confirmed Chikungunya reported from March 2016 to December 2020 in Vitória, Espírito Santo state, Brazil.

Kinin B1- and B2-Receptor Subtypes Contract Isolated Bovine Ciliary Muscle: Their Role in Ocular Lens Function and Intraocular Pressure Reduction.

Bradykinin is an endogenously produced nonapeptide with many physiological and pathological functions that are mediated by two pharmacologically defined receptor subtypes, B1- and B2-receptors. Current studies sought to characterize the functional bradykinin (BK) receptors present in freshly isolated bovine ciliary muscle (BCM) using an organ-bath tissue contraction system. Cumulative longitudinal isometric tension responses of BCM strips (4-5 mm) were recorded before and after the addition of test compounds to BCM strips hooked up to an isometric strain gauge transducer system.