Merck & Co., Inc., Rahway, NJ, USA (United States)

Simulating Directed Evolution In Silico with an Iterative, Physics-Based Workflow

Abstract Directed evolution consistently delivers engineered enzymes that facilitate diverse biocatalytic transformations. Despite advances in automation and high-throughput workflows, our ability to rapidly engineer novel enzymes is limited by our inability to thoroughly sample...

Area-Level Disparities in Pneumococcal Vaccination Among Publicly Insured US Adults: 2016-2019

Objectives: Understanding pneumococcal vaccine uptake across county-level social vulnerability is important for identifying geographic disparities and informing strategies to increase vaccine uptake and reduce the incidence of pneumococcal disease (PD). Using a retrospective coho...

Automated Electrostatic Attraction/Repulsion Hydrophilic Interaction Liquid Chromatography Screening for Polar and Charged Analytes in Complex Matrices

Abstract Electrostatic repulsion hydrophilic interaction liquid chromatography (ERLIC) provides unique selectivity for highly polar and charged analytes, yet method development remains challenging. Careful optimization of organic solvent gradients and buffer concentrations is ess...

Open-label Phase 1 study to evaluate drug-drug interactions between ulonivirine and islatravir in adults without HIV

ABSTRACT Ulonivirine is a non-nucleoside reverse transcriptase inhibitor in clinical development for once-weekly oral treatment of HIV-1 in combination with islatravir. This open-label, 3-period, Phase 1 study (MK-8507-016, NCT06619678) in adults without HIV evaluated the potenti...

Frespaciguat ( MK-5475 ): A Novel Inhaled Soluble Guanylate Cyclase Stimulator for Pulmonary Hypertension Associated with COPD

Abstract Soluble guanylate cyclase (sGC) stimulators are a validated therapeutic approach for pulmonary vasodilation; however, oral agents can cause systemic hypotension and may worsen ventilation-perfusion mismatch in pulmonary hypertension associated with chronic obstructive pu...

Platform‐Specific Immunoassay Development and Orthogonal Characterization for Improved Host Cell Protein Control in Vero Cell‐Derived Vaccines

Vero host cell proteins (HCPs) are critical process-related impurities in Vero cell-derived vaccines and require robust analytical control to support product quality, safety, and manufacturing consistency. During development of the V590 vaccine candidate, discontinuation of the o...

Real-world ctDNA test utilization and associated costs in US patients with bladder cancer who underwent radical cystectomy

BACKGROUND: Circulating tumor DNA (ctDNA) can inform prognosis and treatment effectiveness in bladder cancer. We evaluated real-world utilization and costs of ctDNA testing among US patients with bladder cancer undergoing radical cystectomy following initiation of Medicare covera...

Comparative Renal Effectiveness of GLP-1RA and SGLT2i in US Veterans with Type 2 Diabetes and CKD

Objective: To address limited comparative evidence in older, clinically complex patients with type 2 diabetes and moderate-to-advanced chronic kidney disease (CKD), we compared nephroprotective outcomes after GLP-1RA versus SGLT2i initiation among US Veterans aged ≥65 years with...

Companion diagnostics for pembrolizumab in patients with dMMR/MSI-H tumors

Pembrolizumab is approved in the US for unresectable or metastatic mismatch repair–deficient (dMMR)/microsatellite instability–high (MSI-H) solid tumors that progressed after prior treatment and with no satisfactory alternative treatment options. As part of post-marketing commitm...

IL-2 mutein selectively expands thymic memory Tregs with increased transendocytosis activity in healthy participants

Tregs play an essential role in immune tolerance, and Treg-promoting therapies are in development for the treatment of many inflammatory disorders. Interleukin-2 (IL-2)-based therapies increase Treg frequency, but little is known about impacts on Treg heterogeneity and function....

Structure-Based Drug Design of Quinoline CYP8B1 Inhibitors for the Potential Treatment of Metabolic Disease

Abstract CYP8B1 has been identified as a potential target for the treatment of metabolic diseases, such as nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D). CYP8B1 enzyme inhibitor 1 was discovered from a high-throughput screen of our compound collection; howeve...

Effects of days on feed and trenbolone acetate + estradiol 17-β implantation on empty body composition and retained energy of Charolais × Angus steers across serially slaughtered endpoints

ABSTRACT Objective The objective of this experiment was to evaluate the effects of feeding duration and trenbolone ac-etate + estradiol 17-β implantation on empty body com-position of Charolais × Angus steers. Materials and Methods Pairs of Charolais × Angus steers (n = 80; BW of...

Dual plasmepsin IX and X inhibitors are refractory to development of resistance

Abstract Artemisinin-based combination therapies (ACTs) remain the cornerstone of malaria treatment, but emerging resistance threatens their efficacy. The potential for the development of drug resistance against plasmepsin X (PMX)-selective inhibitors and dual plasmepsin IX/X (PM...

The Randomization Effect in a Double-Blind Placebo-Controlled Depression Study

BACKGROUND: Double-blind, placebo-controlled trials are often affected by higher-than-anticipated placebo responses that may contribute to study failure. It is common to observe symptomatic improvement immediately after randomization regardless of treatment allocation. METHODS: T...

Incidence of Invasive Pneumococcal Disease in US Children by Risk Group, 1998-2023

Abstract Background Children with risk conditions are vulnerable to invasive pneumococcal disease (IPD) and are targeted for routine and supplemental pneumococcal vaccination. This study aimed to quantify the incidence of IPD in US children by risk group since PCV introduction. M...

History of worsening heart failure and outcomes with vericiguat in ambulatory HFrEF: an exploratory post-hoc analysis of VICTOR

Stefan Störk, Javed Butler, Caroline Morbach, Fabian Kerwagen, Johann Bauersachs, Ephraim B Winzer, Justin Ezekowitz, Carolyn S P Lam, Inga Bayh, Stefan He

The health and economic burden of invasive pneumococcal diseases attributable to PCV21 versus PCV20 serotypes among adults aged ≥ 45 years in Spain

Abstract Background The 21-valent pneumococcal conjugate vaccine (PCV21) is a new vaccine that includes eight serotypes not found in any currently licensed vaccines. This study estimates the lifetime clinical and economic burden of invasive pneumococcal disease (IPD) in Spain att...

Dose-Exposure-Response Modeling: Methods and Practical Implementation, 2nd ed

Jixian Wang. Boca Raton, FL: Chapman & Hall/CRC Press, 2026, xvi + 345 pp., $ 166.99(H), ISBN: 978-1-032-59625-9.This is the second edition of Jixian Wang’s book on exposure-response modeling, now ...

A new standard for lyophilizer characterization, comparability and efficient technology transfers

This paper details the implementation of the ΔT and ΔP methodologies—recently introduced in the literature—for monitoring of mass flow during sublimation, demonstrating their application across multiple pharmaceutical companies. As a relatively new approach, this work is assessin...

Trends in vaccination in pharmacy and medical settings among Medicaid recipients in the United States, 2018–2023: a claims analysis

BACKGROUND: Medicaid beneficiaries typically have low vaccination rates, in part due to limited access. Pharmacies provide easy-to-access locations for vaccination. RESEARCH DESIGN AND METHODS: This was a retrospective analysis of trends in pharmacy-based vaccination by age and r...