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Alkalinity-enhanced artificial substrates modulate local pH and increase survivorship of early-stage coral recruits
No full textData files used in the manuscript "Alkalinity enhanced artificial substrates modulate local pH and increase survivorship of early-stage coral recruits". Includes raw data and analysis codes, as well as processed data used for statistical analysis and figure generation.
Targeting APE1-Redox Function Reverses SOX9-mediated Chemoresistance in Esophageal Adenocarcinoma
No full textGastroesophageal reflux disease is the leading risk factor for esophageal adenocarcinoma (EAC), a malignancy that exhibits marked resistance to chemotherapy and results in poor clinical outcomes. This study aims to define and overcome the mechanisms underlying chemoresistance in EAC to enable the development of novel therapeutic strategies.
The study included analysis of RNA sequencing and public datasets. Experimental models consisted of 3-dimensional organotypic cultures, tumorospheres, patient-derived organoids, and de-identified tissue microarrays. In vivo experiments utilized the pL2-IL1β, Krt7CreER;R26rtTA;otet-CDX2, and patient-derived xenograft mouse models.
RNA sequencing revealed a significant enrichment of the SRY-Box Transcription Factor 9 (SOX9) molecular signature in patients with EAC. We identified an apurinic/apyrimidinic endonuclease (APE1)-dependent mechanism that activates SOX9 signaling on exposure to acidic bile salts, mimicking reflux conditions. Genetic knockdown or pharmacological inhibition of APE1's redox activity suppressed SOX9 activation under both reflux-mimicking conditions and oxaliplatin treatment. The redox function of APE1 was required to stabilize the SOX9 protein. Immunostaining demonstrated co-overexpression of APE1 and SOX9 in mouse and human EAC lesions, accompanied by Aldehyde Dehydrogenase 1 Family Member A1 expression, a SOX9 transcriptional target implicated in chemotherapeutic resistance. Clinically, patients with high SOX9 signature expression had significantly worse relapse-free survival. Moreover, in vivo treatment with the APE1-redox-specific inhibitor APX2009 enhanced the response of patient-derived xenograft tumors to oxaliplatin by downregulating SOX9.
Activation of SOX9 through the APE1-redox function is a key driver of EAC chemoresistance. Targeting APE1's redox activity offers a promising therapeutic strategy to overcome resistance by inhibiting the otherwise "undruggable" SOX9 transcription network
Optimal maternal feeding isotopic niche: influence of breeder trophic behaviour on larval growth and survival in bluefin tuna species
No full textMaternal effects play a fundamental role in shaping early larval growth and survival in marine fishes. This study explores the relationship between maternal trophic ecology and larval growth in bluefin tunas, with a focus on Southern Bluefin Tuna (SBT) and an expanded dataset from multiple Atlantic Bluefin Tuna (ABT) populations incorporated into the General Bluefin Model (GBM). Daily growth and stable isotopes (δ15N and δ13C) were obtained from 80 pre-flexion SBT larvae and 355 pre-flexion larvae from the GBM dataset. Results revealed a significant negative linear trend between larval age and δ15N values, consistent with the gradual attenuation of maternally inherited isotopic signatures during development. Faster growing larvae showed significantly lower δ15N and δ13C values, indicating that maternal trophic behaviour and prey sources critically influence larval growth potential. Maternal isotopic niche breadth, inferred from larval isotope data, was markedly narrower in groups with optimal larval growth, suggesting that specialized (stenophagous) maternal feeding strategies promote enhanced offspring performance. These patterns were observed consistently in two bluefin species across seven different populations, despite geographic and temporal variability, highlighting a robust ecological link between maternal foraging behaviour and larval development. From these findings, we introduce the hypothesis of an Optimal Maternal Feeding Isotopic Niche, representing a constrained isotopic range associated with increased larval growth and survival. This framework advances our understanding of the influence of maternal trophic ecology on offspring fitness and offers valuable insights for the conservation and management of highly migratory pelagic species with complex reproductive strategies
Expanding the Test-to-PrEP Strategy: Including People With HIV in Social Network-Based HIV Testing and PrEP Outreach, Miami, Florida, and San Juan, Puerto Rico, June 2024 to February 2025
No full textThis study assesses expansion of the "Test-to-PrEP" (T2P) social network strategy to include people with HIV (PWH) as distributors of HIV self-test kits (HIVST) and PrEP/HIV treatment resources, in Miami and a newly introduced site in San Juan. PWH showed strong interest despite perceived barriers such as stigma. Stakeholders found the strategy acceptable and compatible. Findings highlight the potential of PWH-led T2P implementation to advance HIV prevention and treatment, underscoring the need to support scale-up and address barriers. (. 2026;116(S1):S32-S35. https://doi.org/10.2105/AJPH.2025.308320)
Preferences for Game-Based Elements to Increase Preexposure Prophylaxis and HIV Prevention Engagement Among Latino Men Who Have Sex With Men: South Florida, 2022
No full textWe explored gaming elements as a tool to promote engagement in HIV prevention services among Latino men who have sex with men. We conducted thematic content analysis of semistructured interview data that we collected from 12 Latino men who have sex with men (April-August 2022) in South Florida. Themes emerged related to intervention delivery, components, and perceptions. Our findings will guide the development of a game-based intervention to improve preexposure prophylaxis and HIV prevention engagement among Latino men who have sex with men. (. 2026;116(S1):S10-S15. https://doi.org/10.2105/AJPH.2025.308353)
Pathological Assessment of Metastatic Disease to the Musculoskeletal System
No full textThe musculoskeletal system is a common site for metastases in advanced cancer. Metastases are associated with poor prognosis, and their detection is crucial for proper treatment. Accurate classification of neoplasms in cases of unknown primary tumors is essential to guide management. Clinical and radiological correlation, along with detailed histological analysis, immunohistochemical evaluation, and genetic testing are often required to achieve this goal