Late-stage installation and functionalization of alkyl pyridiniums: a general HTE amenable strategy to access diverse aryl alanine containing macrocyclic peptides.

This manuscript describes a strategy to readily access diverse aryl and homoaryl alanine-containing pharmaceutically relevant macrocyclic peptides. A two-step sequence involving the late-stage installation of the pyridinium functionality on macrocyclic peptides followed by reductive couplings was implemented. These transformations are amenable to microscale high-throughput experimentation (HTE) and enable rapid access to aryl alanine-containing macrocyclic peptides that would otherwise be inaccessible solid-phase peptide synthesis using commercially available amino acids.

Perspectives on Conducting Behavioral Intervention With Adolescents Using a Virtual Platform-A Thematic Analysis From the Viewpoint of Study Coordinators.

Background: The COVID-19 pandemic led to widespread adoption of virtual communication platforms. Virtual study visits were implemented in the pilot cluster randomized trial (CRT) stage of Teen Adherence in KidnEy transplant Improving Tracking To Optimize Outcomes (TAKE-IT TOO). The present study aimed to understand study coordinators' perspectives on conducting a behavioral intervention with adolescent kidney transplant recipients using virtual conferencing platforms.

Emergency department-initiated oral naltrexone for patients with moderate to severe alcohol use disorder: A pilot feasibility study.

Objectives: Alcohol use disorder (AUD) is the most common substance use disorder in the United States. Despite availability of four FDA-approved medications, fewer than 10% of patients are prescribed medication. This study aimed to evaluate the impact and feasibility of emergency department (ED)-initiated oral naltrexone in patients with moderate to severe AUD.

Irritability and Social Media Use in US Adults.

Importance: Efforts to understand the complex association between social media use and mental health have focused on depression, with little investigation of other forms of negative affect, such as irritability and anxiety.

Objective: To characterize the association between self-reported use of individual social media platforms and irritability among US adults.

Design, Setting, And Participants: This survey study analyzed data from 2 waves of the COVID States Project, a nonprobability web-based survey conducted between November 2, 2023, and January 8, 2024, and applied multiple linear regression models to estimate associations with irritability.

Anticipatory Violence and Health Among Black Adults in the United States.

This study analyzes the relationship between anticipatory community and police violence and health outcomes including mental and physical well-being, sleep problems, and functional disability. Using data from a nationally representative survey of 3015 self-identified Black and African American adults in the USA collected in 2023, findings from a series of regression analyses reveal that anticipating community violence is linked to poorer self-rated health and increased sleep problems. Anticipatory police violence is associated with poorer physical health and sleep disturbances.

Neuroligin-3 R451C induces gain-of-function gene expression in astroglia in an astroglia-enriched brain organoid model.

Astroglia are integral to brain development and the emergence of neurodevelopmental disorders. However, studying the pathophysiology of human astroglia using brain organoid models has been hindered by inefficient astrogliogenesis. In this study, we introduce a robust method for generating astroglia-enriched organoids through BMP4 treatment during the neural differentiation phase of organoid development.

Thermodynamics of nucleosome breathing and positioning.

Nucleosomes are fundamental units of chromatin in which a length of genomic DNA is wrapped around a histone octamer spool in a left-handed superhelix. Large-scale nucleosome maps show a wide distribution of DNA wrapping lengths, which in some cases are tens of base pairs (bp) shorter than the 147 bp canonical wrapping length observed in nucleosome crystal structures. Here, we develop a thermodynamic model that assumes a constant free energy cost of unwrapping a nucleosomal bp.

Patient-Reported Improvements in Patients with PNH Treated with Iptacopan from Two Phase 3 Studies.

Iptacopan, a first-in-class, oral, selective complement factor B inhibitor, demonstrated efficacy and safety as monotherapy in C5 inhibitor (C5i)-experienced (APPLY-PNH [NCT04558918]) and C5i-naive (APPOINT-PNH [NCT04820530]) patients with paroxysmal nocturnal hemoglobinuria (PNH). In APPLY-PNH and APPOINT-PNH, changes in fatigue (FACIT-Fatigue) and health-related quality of life (HRQOL; EORTC QLQ-C30) from baseline to Day 168 were evaluated. The proportion of patients achieving meaningful within-patient change (MWPC) on the FACIT-Fatigue and 4 EORTC QLQ-C30 subscales (physical functioning, role functioning, fatigue, dyspnea) was evaluated using anchor-based thresholds.

The WAVE complex in developmental and adulthood brain disorders.

Actin polymerization and depolymerization are fundamental cellular processes required not only for the embryonic and postnatal development of the brain but also for the maintenance of neuronal plasticity and survival in the adult and aging brain. The orchestrated organization of actin filaments is controlled by various actin regulatory proteins. Wiskott‒Aldrich syndrome protein-family verprolin-homologous protein (WAVE) members are key activators of ARP2/3 complex-mediated actin polymerization.

Analytical performance of OncoPrism-HNSCC, an RNA-based assay to inform immune checkpoint inhibitor treatment decisions for recurrent/metastatic head and neck squamous cell carcinoma.

Background: While immune checkpoint inhibitor (ICI) therapies can significantly improve outcomes for patients with recurrent/metastatic head and neck squamous cell carcinoma (RM-HNSCC), only about 15-20% benefit from such treatments. Clinical tests that guide the use of ICIs are therefore critically needed. OncoPrism-HNSCC was developed to address this need.

An Explanatory Mixed-methods Study of "ICU net benefit": Triage and Trajectory for Sepsis and Acute Respiratory Failure.

Rationale: Patients with sepsis and/or acute respiratory failure are at high risk for death or long hospital stays, yet limited evidence exists to guide triage to intensive care units (ICUs) or general medical wards for the majority of these patients who do not initially require life support.

Objectives: To identify factors that influence how hospitals triage patients with capacity-sensitive conditions and those factors that may account for observed ICU relative to ward, or ward relative to ICU, benefits for such patients.

Methods: We conducted an explanatory sequential mixed-methods study.

Establishing a new human pneumococcal standard reference serum, MPRSS-01.

Measuring the immunogenicity of pneumococcal vaccines involves the use of immunoassays to measure serotype-specific immunoglobulin G (IgG) antibody levels post-vaccination with the current human reference serum standard (007sp) for anti-pneumococcal capsule antibodies. Development of new pneumococcal conjugate vaccines (PCVs) with additional serotypes not in 007sp (e.g.

p Matching Enables Quantum Proton Delocalization in Acid-1-Methylimidazole Binary Mixtures.

Short hydrogen bonds (SHBs), characterized by donor-acceptor heteroatom separations below 2.7 Å, are prevalent in condensed-phase systems. Recently, we identified SHBs in nonaqueous binary mixtures of acetic acid and 1-methylimidazole (MIm), where electronic and nuclear quantum effects facilitate extensive proton delocalization.

Development of a Population Pharmacokinetic Gabapentin Model Leveraging Therapeutic Drug Monitoring Concentrations.

Gabapentin has variable pharmacokinetics (PK), which contributes to difficulty in dosing and increased risk of adverse events. The objective of this study was to leverage gabapentin concentrations from therapeutic drug monitoring (TDM) to develop a population PK (popPK) model and characterize significant covariates that impact gabapentin PK. Data were retrospectively collected from 82 hospitalized adult patients with TDM gabapentin concentrations.

The Camden Study-A Pregnancy Cohort Study of Pregnancy Complications and Birth Outcomes in Camden, New Jersey, USA.

Background: Pregnancy is a unique stage of the life course characterized by trade-offs between the nutritional, immune, and metabolic needs of the mother and fetus. The Camden Study was originally initiated to examine nutritional status, growth, and birth outcomes in adolescent pregnancies and expanded to study dietary and molecular predictors of pregnancy complications and birth outcomes in young women.

Methods: From 1985-2006, 4765 pregnant participants aged 12 years and older were recruited from Camden, NJ, one of the poorest cities in the US.

New Strains of the Entomopathogenic Nematodes , , and for White Grub Management.

White grubs possess natural defense mechanisms against entomopathogenic nematodes (EPNs). Hence, EPN isolates that naturally infect white grubs tend to be among the most effective biological control agents of white grubs. We tested the virulence of four EPN isolates recently isolated from infected white grubs in turfgrass areas in central New Jersey, USA against third-instar larvae of , , and , which are pests of turfgrass and ornamental plants in the northeastern USA.

Genetic Variant Analyses Identify Novel Candidate Autism Risk Genes from a Highly Consanguineous Cohort of 104 Families from Oman.

Deficits in social communication, restricted interests, and repetitive behaviours are hallmarks of autism spectrum disorder (ASD). Despite high genetic heritability, the majority of clinically diagnosed ASD cases have unknown genetic origins. We performed genome sequencing on mothers, fathers, and affected individuals from 104 families with ASD in Oman, a Middle Eastern country underrepresented in international genetic studies.

Is There a Role for Surgery in the Treatment of Metastatic Urothelial Carcinoma?

: Bladder cancer is one of the most common malignancies worldwide with over 614,000 new cases and 220,000 deaths annually. Five percent of newly diagnosed patients have metastatic disease. Metastatic urothelial carcinoma (mUC) is primarily treated with cisplatin-based chemotherapy, immunotherapy, targeted therapy, or combinations.

Relationships Among Soda and Energy Drink Consumption, Substance Use, Mental Health and Risk-Taking Behavior in Adolescents.

: Energy drink (ED) use is increasing among children and adolescents, but little is known about the impacts on health, including substance use and mental health. The purpose of this study was to examine the relationship between soda and ED consumption and substance use, mental health, and risk taking in a nationally representative sample of high school students. We used data from the 2019 Youth Risk Behavior Surveillance System (YRBS) from New Jersey, Montana, and Florida to assess these relationships using binary and multinomial regression analyses to determine odds ratios, comparing non-consumers with daily consumers.

Galantamine-Memantine Combination in the Treatment of Parkinson's Disease Dementia.

Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects over 1% of population over age 60. It is defined by motor and nonmotor symptoms including a spectrum of cognitive impairments known as Parkinson's disease dementia (PDD). Currently, the only US Food and Drug Administration-approved treatment for PDD is rivastigmine, which inhibits acetylcholinesterase and butyrylcholinesterase increasing the level of acetylcholine in the brain.

Higher-Order DNA Secondary Structures and Their Transformations: The Hidden Complexities of Tetrad and Quadruplex DNA Structures, Complexes, and Modulatory Interactions Induced by Strand Invasion Events.

We demonstrate that a short oligonucleotide complementary to a G-quadruplex domain can invade this iconic, noncanonical DNA secondary structure in ways that profoundly influence the properties and differential occupancies of the resulting DNA polymorphic products. Our spectroscopic mapping of the conformational space of the associated reactants and products, both before and after strand invasion, yield unanticipated outcomes which reveal several overarching features. First, strand invasion induces the disruption of DNA secondary structural elements in both the invading strand (which can assume an iDNA tetrad structure) and the invaded species (a G-quadruplex).

Chemokine CXCL12 Activates CXC Receptor 4 Metastasis Signaling Through the Upregulation of a CXCL12/CXCR4/MDMX (MDM4) Axis.

Background: The metastasis-promoting G-protein-coupled receptor CXC Receptor 4 (CXCR4) is activated by the chemokine CXCL12, also known as stromal cell-derived factor 1 (SDF-1). The CXCL12/CXCR4 pathway in cancer promotes metastasis but the molecular details of how this pathway cross-talks with oncogenes are understudied. An oncogene pathway known to promote breast cancer metastasis in MDA-MB-231 xenografts is that of Mouse Double Minute 2 and 4 (MDM2 and MDM4, also known as MDMX).

Sequential Endoluminal Doxorubicin and Gemcitabine Alternating Weekly with Sequential Mitomycin and Docetaxel for Recurrent Non-Muscle Invasive Urothelial Carcinoma.

After first-line treatment failure, patients with non-muscle invasive urothelial carcinoma (NMIUC) are recommended to undergo radical cystectomy. However, those unable to pursue radical surgery or desiring bladder preservation require effective salvage therapies. Multi-agent treatment regimens are particularly useful for targeting the complex resistance mechanisms of recurrent UC.