3 research outputs found
ABORTO NO CASO DE GRAVIDEZ RESULTANTE DE ESTUPRO: O PRAZO DE ESCOLHA PARA A VÍTIMA
Get PDFEm suma, o presente trabalho tem por objetivo responder ao seguinte questionamento: Ofende a dignidade da pessoa humana o fato de inexistir prazo legal para que a vítima possa realizar o aborto legal? O artigo faz um comparativo entre o entendimento jurídico e o entendimento da medicina, demonstrando que o parecer medicinal estipula um prazo para a interrupção da gravidez e também tende a solicitar documentos legais como prova do que ocorreu com a vítima, enquanto o âmbito jurídico só prevê a retirada do feto, não impondo qualquer prazo para realizar a interrupção da gravidez ou até mesmo algum documento para que a vítima comprove a violência sexual sofrida. Serão abordados conceitos doutrinários e jurisprudenciais, além de projetos de lei já em tramitação e também abordará pesquisas que analisam a realidade nos hospitais de todo o país para assim equacionar o problema apresentado, na tentativa de criar uma solução para o conflito
from Machine Learning Screening to In Vivo Efficacy
Get PDF© 2025 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.Despite improvements in cancer survival rates, metastatic and surgery-resistant cancers, such as pancreatic cancer, remain challenging, with poor prognoses and limited treatment options. Enhancing drug bioavailability in tumors, while minimizing off-target effects, is crucial. Metal-organic frameworks (MOFs) have emerged as promising drug delivery vehicles owing to their high loading capacity, biocompatibility, and functional tunability. However, the vast chemical diversity of MOFs complicates the rational design of biocompatible materials. This study employed machine learning and molecular simulations to identify MOFs suitable for encapsulating gemcitabine, paclitaxel, and SN-38, and identified PCN-222 as an optimal candidate. Following drug loading, MOF formulations are improved for colloidal stability and biocompatibility. In vitro studies on pancreatic cancer cell lines have shown high biocompatibility, cellular internalization, and delayed drug release. Long-term stability tests demonstrated a consistent performance over 12 months. In vivo studies in pancreatic tumor-bearing mice revealed that paclitaxel-loaded PCN-222, particularly with a hydrogel for local administration, significantly reduced metastatic spread and tumor growth compared to the free drug. These findings underscore the potential of PCN-222 as an effective drug delivery system for the treatment of hard-to-treat cancers.publishersversionepub_ahead_of_prin
Multiscale Profiling of Nanoscale Metal-Organic Framework Biocompatibility and Immune Interactions
Get PDFFunding Information: D.F.\u2010J. thanks the Royal Society for funding through University Research Fellowships and the European Research Council (ERC) under the European Union's Horizon 2020 Research and Innovation Programme (NanoMOFdeli), ERC\u20102016\u2010COG 726380. The authors thank the EPSRC (grant EP/S009000/1). D.M. acknowledges NanoDTC Cambridge \u2013 EPSRC EP/S022953/1. X.L. acknowledges funding from Asthma + Lung UK (previously the British Lung Foundation). The authors are thankful for the technical support from the Cellular Imaging and Analysis Facility at the Department of Veterinary Medicine, University of Cambridge. The authors acknowledge the Laborat\u00F3rio de An\u00E1lises/REQUIMTE/LAQV for the acquisition of the ICP\u2010OES data. Publisher Copyright: © 2025 The Author(s). Advanced Healthcare Materials published by Wiley-VCH GmbH.The clinical translation of metal-organic frameworks (MOFs) – a promising class of porous materials for nanomedicine – is hindered by a poor understanding of their complex interactions with the immune system and in vivo immunotoxicity. To address this gap, a hierarchical “Safety-by-Design” pipeline is established and validated, integrating machine learning (ML) with ex vivo human blood studies and targeted in vivo models. This multi-stage workflow enables the systematic profiling of MOF immunotoxicity, de-risking their development. The power of this approach is demonstrated using four clinically relevant MOFs – NU-901, PCN-222, UiO-66, and ZIF-8 – revealing distinct, framework-dependent immune fingerprints. The initial in silico screening correctly flagged NU-901 and ZIF-8 as potential hazards to human health. These predictions are subsequently validated ex vivo, where NU-901 is confirmed to be selectively cytotoxic to CD14+ monocytes, and ZIF-8 is identified as a specific pro-inflammatory agent via IL-6 induction. In contrast, candidates predicted to be safe – UiO-66 and PCN-222 – demonstrated high biocompatibility ex vivo and advanced to in vivo studies, where they caused only minimal and transient immune activation. This study provides a validated, resource-efficient roadmap for preclinical immunotoxicity assessment, establishing a rational paradigm to accelerate the safe clinical translation of MOFs and other advanced nanomedicines.publishersversioninpres
