Validation of an Epigenetic Prognostic Assay to Accurately Risk-Stratify Patients with Barrett Esophagus

INTRODUCTION: Esophageal adenocarcinoma (EAC) is the second-most lethal cancer in the United States, with Barrett esophagus (BE) being the strongest risk factor. Assessing the future risk of neoplastic progression in patients with BE is difficult; however, high-grade dysplasia (HGD) and early EAC are treatable by endoscopic eradication therapy (EET), with survival rates of 90%. Thus, it would be beneficial to develop a molecular assay to identify high-risk patients, who merit more frequent endoscopic surveillance or EET, as well as low-risk patients, who can avoid EET and undergo less frequent surveillance.METHODS: Deidentified endoscopic biopsies were acquired from 240 patients with BE at 6 centers and confirmed as future progressors or nonprogressors. Tissues were analyzed by a set of methylation-specific biomarker assays. Test performance was assessed in an independent validation set using 4 stratification levels: low risks, low-moderate risks, high-moderate risks, and high risks.RESULTS: Relative to patients in the low-risk group, high-risk patients were 15.2 times more likely to progress within 5 years to HGD or EAC. For patients in the high-risk category, the average risk of progressing to HGD or EAC within 5 years was 21.5%, 4-fold the BE population prevalence within 5 years, whereas low-risk patients had a progression risk of only 1.85%.DISCUSSION: This clinical assay, Esopredict, stratifies future neoplastic progression risk to identify higher-risk patients with BE who can benefit from EET or more frequent surveillance and lower-risk patients who can benefit from reduced surveillance

Functional gene delivery to and across brain vasculature of systemic AAVs with endothelial-specific tropism in rodents and broad tropism in primates

Delivering genes to and across the brain vasculature efficiently and specifically across species remains a critical challenge for addressing neurological diseases. We have evolved adeno-associated virus (AAV9) capsids into vectors that transduce brain endothelial cells specifically and efficiently following systemic administration in wild-type mice with diverse genetic backgrounds, and in rats. These AAVs also exhibit superior transduction of the CNS across non-human primates (marmosets and rhesus macaques), and in ex vivo human brain slices, although the endothelial tropism is not conserved across species. The capsid modifications translate from AAV9 to other serotypes such as AAV1 and AAV-DJ, enabling serotype switching for sequential AAV administration in mice. We demonstrate that the endothelial-specific mouse capsids can be used to genetically engineer the blood-brain barrier by transforming the mouse brain vasculature into a functional biofactory. We apply this approach to Hevin knockout mice, where AAV-X1-mediated ectopic expression of the synaptogenic protein Sparcl1/Hevin in brain endothelial cells rescued synaptic deficits

Functional gene delivery to and across brain vasculature of systemic AAVs with endothelial-specific tropism in rodents and broad tropism in primates

Delivering genes to and across the brain vasculature efficiently and specifically across species remains a critical challenge for addressing neurological diseases. We have evolved adeno-associated virus (AAV9) capsids into vectors that transduce brain endothelial cells specifically and efficiently following systemic administration in wild-type mice with diverse genetic backgrounds, and in rats. These AAVs also exhibit superior transduction of the CNS across non-human primates (marmosets and rhesus macaques), and in ex vivo human brain slices, although the endothelial tropism is not conserved across species. The capsid modifications translate from AAV9 to other serotypes such as AAV1 and AAV-DJ, enabling serotype switching for sequential AAV administration in mice. We demonstrate that the endothelial-specific mouse capsids can be used to genetically engineer the blood-brain barrier by transforming the mouse brain vasculature into a functional biofactory. We apply this approach to Hevin knockout mice, where AAV-X1-mediated ectopic expression of the synaptogenic protein Sparcl1/Hevin in brain endothelial cells rescued synaptic deficits

Functional enhancer elements drive subclass-selective expression from mouse to primate neocortex

Viral genetic tools to target specific brain cell types in humans and non-genetic model organisms will transform basic neuroscience and targeted gene therapy. Here we used comparative epigenetics to identify thousands of human neuronal subclass-specific putative enhancers to regulate viral tools, and 34% of these were conserved in mouse. We established an AAV platform to evaluate cellular specificity of functional enhancers by multiplexed fluorescent in situ hybridization (FISH) and single cell RNA sequencing. Initial testing in mouse neocortex yields a functional enhancer discovery success rate of over 30%. We identify enhancers with specificity for excitatory and inhibitory classes and subclasses including PVALB, LAMP5, and VIP/LAMP5 cells, some of which maintain specificity in vivo or ex vivo in monkey and human neocortex. Finally, functional enhancers can be proximal or distal to cellular marker genes, conserved or divergent across species, and could yield brain-wide specificity greater than the most selective marker genes

2025 Position statement on active outdoor play

Background: In 2015, the Position Statement on Active Outdoor Play was released in Canada, emphasizing the critical role of active outdoor play—with its risks—in fostering children’s healthy development. Building on this foundation, a 10-year update of the Position Statement on Active Outdoor Play (AOP10) was initiated to broaden its scope and impact, by encompassing all age groups and extending its reach conceptually and globally. Here we explain and present the new 2025 Position Statement. Methods: Development of the 2025 Position Statement was informed by 18 rigorous literature reviews, a series of leadership group meetings, three rounds of draft AOP10 surveys, followed by extensive communication, translation, production, and dissemination activities. Results: The 2025 Position Statement on Active Outdoor Play states: “Active outdoor play promotes holistic health and well-being for people of all ages, communities, and environments, and for our entire planet. It is critical given the multiple global challenges we face today (e.g., social and health inequities, climate change and digital addiction). Together, as a collective of the outdoor play sector, we recommend increasing opportunities for active outdoor play in all settings where people live, learn, work, and play. To achieve this, it is important to collaborate across sectors, settings, and societies to preserve, promote, and value equitable access to active play outdoors and in nature.” We also provide key evidence pertaining to the nine core themes that informed the development of the 2025 Position Statement and offer recommendations across sectors, calling for multi-sectoral, multi-level collaborations. Across all three survey rounds, responses indicated strong support for the 2025 Position Statement and its supporting content (Round 3: 93–98%). Comprehensive, proactive knowledge translation and dissemination plans were executed to maximize the reach and impact of the 2025 Position Statement. Conclusions: The 2025 Position Statement calls for systemic changes that prioritize equitable access to active outdoor play opportunities and aims to create healthier communities. Achieved through international collaboration and consensus, the 2025 Position Statement aspires to connect, advise, inspire, and activate active outdoor play worldwide

Variations and modelling of oxygen demand in amino acid production

The L-lysine fermentation by Brevibacteria lactofermentum was investigated in this study. The objective was to improve the process performance by manipulating cellular environment conditions. The main factor under consideration was dissolved oxygen concentration (DOC) in the broth. To implement effective process control, a process model was developed based on combined kinetic study and material balances. The process dynamics at the dissolved oxygen tensions (DOTs) of 2%, 5%, 10%, and 20% was analysed. The results showed that inhibition of high oxygen level could occur during the very early growth phase and depressive effect of low oxygen availability was confined to the rest of the process, suggesting that different fermentation stages required different DOTs. Batch experiments were conducted with 3% DOT for the first 24 h, 10% for 24-48 h, and 5% for the rest of the fermentation, and the results were compared with those under 20% DOT throughout. The final L-lysine concentration reached 51.4 g/l compared with 45 g/l; the overall yield increased from 0.300g/g to 0.343g/g; and the productivity was improved from 0.616 g/l/h to 0.633 g/l/h. Also importantly, the low DOT settings required much less energy for agitation and aeration

Principles and Applications of Cell Delivery Systems for Periodontal Regeneration

The management of periodontal defects has been an ongoing challenge in clinical periodontics. This is mainly a result of the fact that the tissues which comprise the periodontium, the periodontal ligament, and the cementum and alveolar bone, represent three unique tissues in their own right. Thus, reconstruction of the periodontium is not just a simple matter of regenerating one tissue but involves at least three quite diverse and unique tissues. Resective surgical therapy, with or without osseous recontouring, was considered the norm during the 1950s and into the 1960s, in the belief that attainment of shallow pocket depths was a worthwhile goal. More recently, attention has been focused more on regenerative and reconstructive therapies, rather than on resective therapies. Currently, clinical and scientific research is focusing on a number of approaches for periodontal regeneration

Omstead O\u27s

Omstead O’s is a five-song EP created as the Culminating Experience for the Songwriting and Production Master’s Program at BerkleeNYC. Released under Jack Omstead’s artist name and brand, Born Dude, the project fuses playful pop songwriting, emotional storytelling, and a nostalgic-yet-modern sound influenced by early 2010s pop and hip-hop. More than just a musical project, Omstead O’s comes to life through a custom-designed cereal box and cassette tape, forming a tactile, collectible experience. At its core, the project celebrates the joy, curiosity, and excitement often associated with youth. It stands as both a creative milestone and a launchpad for a larger vision where music and branding intersect to evoke real emotion. Over the course of ten months, Jack’s sonic identity took shape through consistent work both inside and outside of class. Nearly 100 songs were worked on during this period, resulting in a confident selection of tracks presented in Omstead O’s. Jack wrote, produced, mixed, and mastered all five songs while also designing the visual and physical components. This hands-on, multi-disciplinary approach allowed him to build a fully realized world around the music. The project showcases Jack’s commitment to storytelling across mediums and lays the foundation for future work that blends sound, design, and identity into a cohesive, immersive experience.https://remix.berklee.edu/graduate-studies-cmat/1163/thumbnail.jp