Revealing New Analytical Insights into RNA Complexes: Divalent siRNA Characterization by Liquid Chromatography and Mass Spectrometry.

Accurate characterization of therapeutic RNA, including purity and identity, is critical in drug discovery and development. Here, we utilize denaturing and non-denaturing chromatography for the analysis of ∼25 kDa divalent small interfering RNA (di-siRNA), which comprises a complex 2:1 triplex structure. Ion pair reversed-phase (IPRP) liquid chromatography (LC) experiments with UV absorbance and mass spectrometry (MS) showcase a single denaturing LC method for identity confirmation, impurity profiling, and sequencing with automated MS data interpretation.

Pharmacogenetic markers and macrolide safety in influenza patients: insights from a prospective study.

Background: Macrolides are widely used antibiotics, but adverse drug reactions (ADRs), particularly in genetically predisposed individuals, can compromise their safety. This study examines the impact of pharmacogenetic markers on macrolide safety in participants with bacterial complications of influenza.

Objective: To evaluate how polymorphisms in genes encoding transporter proteins (ABCB1) and enzymes (CYP3A4, CYP3A5) influence ADR risk during macrolide therapy.

Mental Health Vulnerabilities and Environmental Justice: A Collaborative Online International Learning Experience.

Collaboration and intercultural interaction and engagement are relevant to all aspects of higher education including distance/remote/virtual courses. Collaborative Online International Learning (COIL) experiences connect students in different countries and provide them with meaningful and significant opportunities for global and intercultural exposure. Such an educational environment enhances students' cultural awareness and knowledge, and guides their personal, relational, and professional actions.

Red blood cell urate levels are linked to hemolysis in vitro and post-transfusion as a function of donor sex, population and genetic polymorphisms in SLC2A9 and ABCG2.

Background: Storage of packed red blood cells (RBCs) for transfusion leads to biochemical and morphological changes, increasing hemolysis risk. Urate levels in blood bags at donation contribute to the molecular heterogeneity and hemolytic propensity of stored RBCs. However, studies to date have been underpowered to investigate at scale the contribution of donor demographics and genetics to the heterogeneity in urate levels across donations.

Proposed resources required for a comprehensive program for CCT CHD imaging.

Background: Cardiac Computed Tomography (CCT) is increasingly used for evaluation of congenital heart disease (CHD) in patients of all ages. Pediatric and adult congenital heart disease (ACHD) surgical programs require high quality CCT imaging as part of the multimodality imaging support expected of comprehensive care centers. Despite these expectations, there are no benchmarks or defined programmatic elements specific to the performance of CCT in patients with CHD.

Experimental tools and emerging principles of organellar mechanotransduction.

Mechanotransduction is the process by which cells detect mechanical forces and convert them into biochemical or electrical signals. This process occurs across various cellular compartments, including the plasma membrane, cytoskeleton, and intracellular organelles. While research has focused mainly on force sensing at the plasma membrane, the mechanisms and significance of intracellular mechanotransduction are just beginning to be understood.

Perianal angiolymphoid hyperplasia with eosinophilia mimicking Kaposi sarcoma in a patient living with HIV.

A woman in her 70s with well-controlled HIV on antiretroviral therapy presented with a several-month history of an asymptomatic perianal lesion. Skin examination showed a 0.5-1 cm red-pink, shiny, exophytic papule with visible telangiectasias near the anal verge.

Advancing precision psychiatry and targeted treatments: Insights from immunopsychiatry.

Despite tremendous advancements in neuroscience, there has been limited impact on patient care. Current psychiatric treatments are largely non-specific, and drug development is hindered by outdated, overinclusive diagnostic categories and a "one-size-fits-all" approach. Additionally, mechanisms underlying psychiatric illnesses and their treatments with conventional medications remain poorly understood.

Residual-attention deep learning model for atrial fibrillation detection from Holter recordings.

Background: Detecting subtle patterns of atrial fibrillation (AF) and irregularities in Holter recordings is intricate and unscalable if done manually. Artificial intelligence-based techniques can be beneficial. In fact, with the rapid advancement of AI, deep learning (DL) demonstrated the capability to identify AF from ECGs with significant performance.

Red blood cell pyruvate kinase properties in Townes and Berkeley sickle cell disease mouse models - Of mice and men.

Pyruvate kinase (PK), a key ATP-generating enzyme in glycolysis, is a target for novel sickle cell disease (SCD) therapies. Enhancing PK activity lowers 2,3-diphosphyglycerate (2,3-DPG), increases adenosine triphosphate (ATP), and may prevent red blood cell (RBC) sickling. Townes and Berkeley SCD mouse models are commonly used for the development of novel drugs for SCD, but differ from humans in 2,3-DPG and ATP levels, which could be related to underlying differences in PK properties.

Modulatory effect of Echium plantagineum oil on the n-3 LC-PUFA biosynthetic capacity of chicken (Gallus gallus).

Poultry can be a sustainable source of eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) through the bioconversion of dietary alpha-linolenic acid (ALA, 18:3n-3). However, this process is currently limited by the high n-6/n-3 ratio in poultry diets affecting the competition between n-6 and n-3 fatty acids (FA) for the same biosynthetic enzymes, and the rate-limiting Δ6 desaturase which act at both, the first and final steps of DHA synthesis pathway. Echium plantagineum oil (EO) is an unusual source of stearidonic acid (SDA, 18:4n-3) which bypasses the first Δ6 desaturase step potentially increasing n-3 long-chain polyunsaturated fatty acids (LC-PUFA) synthesis.

Prenatally Diagnosed Absent Septum Pellucidum and Septo-Optic Dysplasia: A Narrative Review and Practical Recommendations for Pediatric Neurologists.

Evaluation of the cavum septum pellucidum is required in standard second-trimester screening fetal anatomy ultrasound scans. The absence of septum pellucidum triggers further evaluation and referral for subspecialty counseling. Absence of septum pellucidum is linked to other midline anomalies including septo-optic dysplasia.

Comparison of Postoperative Antibiotic Protocols for Pediatric Complicated Appendicitis: A Western Pediatric Surgery Research Consortium Study.

Background: There is no consensus on the appropriate duration of postoperative antibiotics for complicated appendicitis in children. Commonly used antibiotic endpoints include normalization of white blood cell count (WBC) or completion of a minimum number of prespecified treatment days. We compared clinical outcomes resulting from varying postoperative antibiotic protocols for complicated appendicitis in children.

Incomplete human reference genomes can drive false sex biases and expose patient-identifying information in metagenomic data.

As next-generation sequencing technologies produce deeper genome coverages at lower costs, there is a critical need for reliable computational host DNA removal in metagenomic data. We find that insufficient host filtration using prior human genome references can introduce false sex biases and inadvertently permit flow-through of host-specific DNA during bioinformatic analyses, which could be exploited for individual identification. To address these issues, we introduce and benchmark three host filtration methods of varying throughput, with concomitant applications across low biomass samples such as skin and high microbial biomass datasets including fecal samples.

The 2024 American Association for Thoracic Surgery expert consensus document: Current standards in donor lung procurement and preservation.

Background: Donor lung procurement and preservation is critical for lung transplantation success. Unfortunately, the large variability in techniques impacts organ utilization rates and transplantation outcomes. Compounding this variation, recent developments in cold static preservation and new technological advances with machine perfusion have increased the complexity of the procedure.

Primary Antibody Deficiencies: Curation Of Gene-Disease Relationships Using A ClinGen Validation Framework.

Background: The Clinical Genome Resource (ClinGen) is an international collaborative effort between scientists and clinicians, diagnostic and research laboratories as well as the patient community. Using a standardized framework, ClinGen has established guidelines to classify gene-disease relationships as Definitive, Strong, Moderate, and Limited based on available scientific and clinical evidence. When the genetic and functional evidence for a gene-disease relationship has conflicting interpretations or contradictory evidence, they can be Disputed or Refuted.

International Expert-Based Consensus Definition, Classification Criteria, and Minimum Data Elements for Osteoradionecrosis of the Jaw: An Inter-Disciplinary Modified Delphi Study.

Purpose: Osteoradionecrosis of the jaw (ORNJ) is a severe iatrogenic disease characterized by bone death after radiation therapy (RT) to the head and neck. With over 9 published definitions and at least 16 classification systems, the true incidence and severity of ORNJ are obscured by lack of a standard for disease definition and severity assessment, leading to inaccurate estimation of incidence, reporting ambiguity, and likely under-diagnosis worldwide. This study aimed to achieve consensus on an explicit definition and phenotype of ORNJ and related precursor states through data standardization to facilitate effective diagnosis, monitoring, and multidisciplinary management of ORNJ.

Adapting to evolving MRI data: A transfer learning approach for Alzheimer's disease prediction.

Integrating 3D magnetic resonance imaging (MRI) with machine learning has shown promising results in healthcare, especially in detecting Alzheimer's Disease (AD). However, changes in MRI technologies and acquisition protocols often yield limited data, leading to potential overfitting. This study explores Transfer Learning (TL) approaches to enhance AD diagnosis using a Baseline model consisting of a 3D-Convolutional Neural Network trained on 80 3T MRI scans.

Transporter Expressions as Part of Required Scaling Factor to Support In vitro In vivo Extrapolation for Blood-Brain Barrier Drug Permeability.

Access of drugs to the central nervous system is limited by the blood-brain barrier, and this in turn affects drug efficacy/toxicity. To date, most drug discovery optimization paradigms have relied heavily on in vitro transporter assays and preclinical species pharmacokinetic evaluation to provide a qualitative assessment of human brain penetration. Because of the lack of human brain pharmacokinetic data, mechanistic models for preclinical species, combined with in vitro and in silico data, are useful for translation to human.