Publications by authors named "Nolan T"

Background: Compared to older adults with breast cancer (BC), adolescents and young adults (AYAs) develop more aggressive disease necessitating more intensive therapy with curative intent, which is disruptive to planned life trajectories. The burden of unmet needs among AYA BC survivors exists in two domains: (1) symptoms (e.g.

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Genetic control - the deliberate introduction of genetic traits to control a pest or vector population - offers a powerful tool to augment conventional mosquito control tools that have been successful in reducing malaria burden but that are compromised by a range of operational challenges. Self-sustaining genetic control strategies have shown great potential in laboratory settings, but hesitancy due to their invasive and persistent nature may delay their implementation. Here, instead, we describe a self-limiting strategy, designed to have geographically and temporally restricted effect, based on a Y chromosome-linked genome editor (YLE).

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Background: A MenABCWY vaccine containing 4CMenB and MenACWY-CRM vaccine components has been developed to protect against the five meningococcal serogroups that cause most invasive disease cases.

Methods: In this phase 3 study (NCT04707391), healthy participants aged 15-25 years, who had received MenACWY vaccination ≥4 years previously, were randomized (1:1) to receive two MenABCWY doses six months apart or one MenACWY-CRM dose. Primary objectives were to demonstrate the non-inferiority of MenABCWY 1 month post-vaccination versus MenACWY-CRM, with a lower limit of 2-sided 95% confidence interval above -10% for group differences in 4-fold rise in human serum bactericidal antibody (hSBA) titers against serogroups ACWY, and to evaluate reactogenicity and safety.

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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.

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Article Synopsis
  • The study evaluates a new meningococcal vaccine (MenABCWY) that combines components of the existing MenB vaccine (4CMenB) and the MenACWY vaccine, aiming to provide broad immunization against various meningococcal strains and ease vaccination schedules.
  • Conducted as a phase 3 randomized trial across multiple countries, healthy participants aged 10-25 were assigned to receive different vaccine schedules to assess safety, immune response, and consistency of vaccine lots.
  • The trial primarily focused on the immune response to MenB strains, comparing MenABCWY's effectiveness to 4CMenB and evaluating the consistency of immune responses among different production lots of the vaccines.
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Background: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States. Early detection via routine CRC screening can significantly lower risks for CRC-specific morbidity and mortality. Public health initiatives between 2000 and 2015 nearly doubled CRC screening rates for some US adults.

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Bacterial infections are a leading cause of mortality worldwide, underscoring the urgent need for effective detection methods. This study introduces a novel approach that combines surface-enhanced Raman spectroscopy (SERS) with an electro-optic technique for bacterial detection. The method utilizes a metal-semiconductor substrate that, when activated by an external electric field, significantly amplifies the SERS signal intensity.

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Article Synopsis
  • Meningococcal serogroup B (MenB) vaccination with the 4CMenB vaccine was tested for its effectiveness and safety among 3,651 healthy participants aged 10 to 25, using different dosing schedules (0-2, 0-6, and 0-2-6 months).
  • The study measured the immune response through two methods: a test-based approach showing high immune breadth (over 78%) and a responder-based approach indicating a significant percentage of participants achieved strong responses (up to 93.4% for the 0-2-6 schedule).
  • The results showed no major differences in effectiveness across the dosing schedules, confirming that the simpler 2-dose regimen (0-2)
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One of the grand challenges in chemical biology is identifying a small-molecule modulator for all proteins within a proteome. To expand the variety and number of ligandable proteins for drug discovery, the objective of this study was to synthesize and evaluate the protein target profiles of electrophilic and photoreactive fully functionalized small-molecule probes (FFSMPs) featuring increased scaffold-, appendage-, and protein-reactive functional group (PRFG) diversity. FFSMPs contain: (1) a protein-binding motif, (2) an electrophilic or photoreactive PRFG for target protein capture, and (3) a terminal alkyne for click chemistry-based proteomic applications.

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Brassinosteroid signaling is essential for plant growth as exemplified by the dwarf phenotype of loss-of-function mutants in (), a ubiquitously expressed Arabidopsis brassinosteroid receptor gene. Complementation of brassinosteroid-blind receptor mutants by expression with various tissue-specific promoters implied that local brassinosteroid signaling may instruct growth non-cell autonomously. Here, we performed such rescues with a panel of receptor variants and promoters, in combination with tissue-specific transgene knockouts.

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This phase 1 trial assessed the safety and immunogenicity of an investigational tetanus/diphtheria/acellular pertussis vaccine combined with CpG 1018 adjuvant 1500 μg (Tdap-1018 1500 μg) or 3000 μg (Tdap-1018 3000 μg) in adults and adolescents. In this randomized, active-controlled, multicenter, dose-escalation trial, healthy participants aged 10 to 22 years received 1 dose of Tdap-1018 1500 μg, Tdap-1018 3000 μg, or Boostrix. Geometric mean concentrations (GMCs) and booster response rates (BRRs) for antibodies against pertussis (pertussis toxin, filamentous hemagglutinin, pertactin), tetanus, and diphtheria antigens, and neutralizing antibodies against pertussis toxin were assessed 4 weeks after vaccination.

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CRISPR-Cas9 homing gene drives are designed to induce a targeted double-stranded DNA break at a wild type allele ('recipient'), which, when repaired by the host cell, is converted to the drive allele from the homologous ('donor') chromosome. Germline localisation of this process leads to super-Mendelian inheritance of the drive and the rapid spread of linked traits, offering a novel strategy for population control through the deliberate release of drive individuals. During the homology-based DNA repair, additional segments of the recipient chromosome may convert to match the donor, potentially impacting carrier fitness and strategy success.

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Following the development of a value of vaccination (VoV) framework for health technology assessment/cost-effectiveness analysis (HTA/CEA), and identification of three vaccination benefits for near-term inclusion in HTA/CEA, this final paper provides decision makers with methods and examples to consider benefits of health systems strengthening (HSS), equity, and macroeconomic gains. Expert working groups, targeted literature reviews, and case studies were used. Opportunity cost methods were applied for HSS benefits of rotavirus vaccination.

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