Methods behind neoantigen prediction for personalized anticancer vaccines.

Next to conventional cancer therapies, immunotherapies such as immune checkpoint inhibitors have broadened the cancer treatment landscape over the past decades. Recent advances in next generation sequencing and bioinformatics technologies have made it possible to identify a patient's own immunogenic neoantigens. These cancer neoantigens serve as important targets for personalized immunotherapy which has the benefit of being more active and effective in targeting cancer cells.

Challenges in neoantigen-directed therapeutics.

A fundamental prerequisite for the efficacy of cancer immunotherapy is the presence of functional, antigen-specific T cells within the tumor. Neoantigen-directed therapy is a promising strategy that aims at targeting the host's immune response against tumor-specific antigens, thereby eradicating cancer cells. Initial forays have been made in clinical environments utilizing vaccines and adoptive cell therapy; however, many challenges lie ahead.

A synthetic DNA template for fast manufacturing of versatile single epitope mRNA.

A flexible, affordable, and rapid vaccine platform is necessary to unlock the potential of personalized cancer vaccines in order to achieve full clinical efficiency. mRNA cancer vaccine manufacture relies on the rigid sequence design of multiepitope constructs produced by laborious bacterial cloning and time-consuming plasmid preparation. Here, we introduce a synthetic DNA template (SDT) assembly process, which allows cost- and time-efficient manufacturing of single (neo)epitope mRNA.

Cocaine-Induced Changes in Sperm Methylation Are Associated with Cocaine Resistance in Male Offspring.

Paternal environmental perturbations can influence the physiology and behavior of offspring. For example, our previous work showed reduced cocaine reinforcement in male, but not female, progeny of rat sires that self-administered cocaine. The information transfer from sire to progeny may occur through epigenetic marks in sperm, encompassing alterations in small noncoding RNAs, including microRNAs (miRNAs) and/or DNA methylation.

Results of the United States Food and Drug Administration Clinical Trial of the CustomFlex Artificial Iris.

Purpose: To evaluate safety and efficacy of a custom-manufactured artificial iris device (CustomFlex Artificial Iris; HumanOptics AG) for the treatment of congenital and acquired iris defects.

Design: Multicenter, prospective, unmasked, nonrandomized, interventional clinical trial.

Participants: Patients with photophobia, sensitivity secondary to partial or complete congenital or acquired iris defects, or both.

Preconception maternal cocaine self-administration increases the reinforcing efficacy of cocaine in male offspring.

Rationale: Although the influence of gestational cocaine exposure on offspring has been the focus of a sustained research effort, the effect of preconception cocaine self-administration by dams on progeny has received far less attention.

Method: In the current study, adult female rats were allowed to self-administer cocaine 2 h a day for 60 days and then after a 10-day wash out period, bred to naïve males. Maternal behavior was measured in dams until weaning.

Novel biomarkers to assess in utero effects of maternal opioid use: First steps toward understanding short- and long-term neurodevelopmental sequelae.

Maternal opioid use disorder is common, resulting in significant neonatal morbidity and cost. Currently, it is not possible to predict which opioid-exposed newborns will require pharmacotherapy for neonatal abstinence syndrome. Further, little is known regarding the effects of maternal opioid use disorder on the developing human brain.

H3.3 Barcoding of Nucleus Accumbens Transcriptional Activity Identifies Novel Molecular Cascades Associated with Cocaine Self-administration in Mice.

Although numerous epigenetic modifications have been associated with addiction, little work has explored the turnover of histone variants. Uniquely, the H3.3 variant incorporates stably and preferentially into chromatin independently of DNA replication at active sites of transcription and transcription factor binding.

Selective expansion of myeloid and NK cells in humanized mice yields human-like vaccine responses.

Mice engrafted with components of a human immune system have become widely-used models for studying aspects of human immunity and disease. However, a defined methodology to objectively measure and compare the quality of the human immune response in different models is lacking. Here, by taking advantage of the highly immunogenic live-attenuated yellow fever virus vaccine YFV-17D, we provide an in-depth comparison of immune responses in human vaccinees, conventional humanized mice, and second generation humanized mice.

Environmental, genetic and epigenetic contributions to cocaine addiction.

Decades of research on cocaine has produced volumes of data that have answered many important questions about the nature of this highly addictive drug. Sadly, none of this information has translated into the development of effective therapies for the treatment of cocaine addiction. This review endeavors to assess the current state of cocaine research in an attempt to identify novel pathways for therapeutic development.

Paternal cocaine taking elicits epigenetic remodeling and memory deficits in male progeny.

This corrects the article DOI: 10.1038/mp.2017.

Paternal cocaine taking elicits epigenetic remodeling and memory deficits in male progeny.

Paternal environmental perturbations including exposure to drugs of abuse can produce profound effects on the physiology and behavior of offspring via epigenetic modifications. Here we show that adult drug-naive male offspring of cocaine-exposed sires have memory formation deficits and associated reductions in NMDA receptor-mediated hippocampal synaptic plasticity. Reduced levels of the endogenous NMDA receptor co-agonist d-serine were accompanied by increased expression of the d-serine degrading enzyme d-amino acid oxidase (Dao1) in the hippocampus of cocaine-sired male progeny.

Results of topography-guided laser in situ keratomileusis custom ablation treatment with a refractive excimer laser.

Purpose: To evaluate the safety and effectiveness of topography-guided custom ablation treatment (T-CAT) to correct myopia and myopic astigmatism with laser in situ keratomileusis (LASIK).

Setting: Nine clinical sites in the USA.

Design: Prospective observational nonrandomized unmasked study.

Otx2 ChIP-seq reveals unique and redundant functions in the mature mouse retina.

During mouse retinal development and into adulthood, the transcription factor Otx2 is expressed in pigment epithelium, photoreceptors and bipolar cells. In the mature retina, Otx2 ablation causes photoreceptor degeneration through a non-cell-autonomous mechanism involving Otx2 function in the supporting RPE. Surprisingly, photoreceptor survival does not require Otx2 expression in the neural retina, where the related Crx homeobox gene, a major regulator of photoreceptor development, is also expressed.

Topographically guided laser in situ keratomileusis for myopia using a customized aspherical treatment zone.

Purpose: To assess the efficacy, predictability, safety, and quality-of-life effects of topography-guided laser in situ keratomileusis (LASIK) for the correction of myopia with astigmatism using the EC-5000 CXII excimer laser equipped with a customized aspheric treatment zone algorithm.

Setting: Ophthalmology clinics in the United States and Mexico.

Methods: In a multicenter United States Food and Drug Administration study of topography-guided LASIK, 4 centers enrolled 135 eyes with a spherical manifest refraction error ranging from -0.

Topographically guided LASIK for myopia using the Nidek CXII customized aspheric treatment zone (CATz).

Purpose: To assess the efficacy, predictability, and safety of topography-guided laser in situ keratomileusis (LASIK) for the surgical correction of low to moderate myopia with astigmatism using the Nidek CXIII excimer laser equipped with the customized aspheric treatment zone (CATz) algorithm.

Methods: In a multicenter US Food and Drug Administration study of topography-guided LASIK, 4 centers enrolled 135 eyes with manifest refraction sphere that ranged from -0.50 to -7.

Laser in situ keratomileusis for spherical hyperopia and hyperopic astigmatism using the NIDEK EC-5000 excimer laser.

Purpose: To assess the efficacy, predictability, and safety of LASIK for the surgical correction of low to moderate hyperopia and hyperopic astigmatism using the NIDEK EC-5000 excimer laser.

Methods: In a multicenter United States Food and Drug Administration (FDA) regulated study of LASIK, 7 centers enrolled 293 eyes with manifest refraction sphere that ranged from +0.50 to +6.