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We submit that the safe operating space of the planetary boundary of novel entities is exceeded since annual production and releases are increasing at a pace that outstrips the global capacity for assessment and monitoring. The novel entities boundary in the planetary boundaries framework refers to entities that are novel in a geological sense and that could have large-scale impacts that threaten the integrity of Earth system processes. We review the scientific literature relevant to quantifying the boundary for novel entities and highlight plastic pollution as a particular aspect of high concern. An impact pathway from production of novel entities to impacts on Earth system processes is presented. We define and apply three criteria for assessment of the suitability of control variables for the boundary: feasibility, relevance, and comprehensiveness. We propose several complementary control variables to capture the complexity of this boundary, while acknowledging major data limitations. We conclude that humanity is currently operating outside the planetary boundary based on the weight-of-evidence for several of these control variables. The increasing rate of production and releases of larger volumes and higher numbers of novel entities with diverse risk potentials exceed societies' ability to conduct safety related assessments and monitoring. We recommend taking urgent action to reduce the harm associated with exceeding the boundary by reducing the production and releases of novel entities, noting that even so, the persistence of many novel entities and/or their associated effects will continue to pose a threat.
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http://dx.doi.org/10.1021/acs.est.1c04158 | DOI Listing |
J Cardiol
September 2025
Catholic Research Institute for Intractable Cardiovascular Disease, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; Department of Cardiology, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. Electronic addr
Heart failure with preserved ejection fraction (HFpEF) accounts for more than half of all HF cases and its incidence and prevalence continue to increase, with a substantial burden of morbidity and mortality. Despite advances in our understanding of heterogeneous pathophysiology underlying HFpEF, the diagnosis, risk assessment, and management of this disease entity remain challenging in everyday practice. Artificial intelligence (AI) algorithm can handle large amounts of complex data and machine learning (ML), a subfield of AI, allows for the identification of relevant patterns by learning from big data.
View Article and Find Full Text PDFGraefes Arch Clin Exp Ophthalmol
September 2025
Department of Ophthalmology, Emory University School of Medicine, 1365B Clifton Road, NE, Suite 2400, Atlanta, GA, 30322, USA.
Purpose: Congenital X-linked retinoschisis (XLRS) has limited treatment options. Gene augmentation via pars plana vitrectomy (PPV) and subretinal RS1 gene delivery is promising, yet it is unclear how PPV may impact outcomes. We explored literature to better understand PPV outcomes in XLRS.
View Article and Find Full Text PDFInt J Pharm
September 2025
School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, United Kingdom. Electronic address:
Nanocrystals (NCs), nano-sized drug particles, offer a promising strategy to enhance the bioavailability of poorly soluble compounds, a challenge that affects 70-90 % of new chemical entities. Among the available production methods, wet media milling is widely adopted due to its scalability and efficiency. However, conventional lab-scale mills often require large suspension volumes and high amounts of drug, limiting their suitability for early-stage development, particularly with novel or scarce compounds.
View Article and Find Full Text PDFAging Cell
September 2025
CREEC/CANECEV, MIVEGEC (CREES) Department, University of Montpellier, CNRS, IRD, Montpellier, France.
Aging, and by extension age-related diseases, has traditionally been understood through classical evolutionary genetic models, such as the mutation accumulation and antagonistic pleiotropy theories. However, these frameworks primarily focus on the declining efficacy of organismal-level selection against mutations with deleterious effects in late life. Here, we propose a novel hypothesis: many chronic diseases associated with aging may emerge, at least in part, as a result of selection acting at lower organizational levels, including non-replicative biological entities, enabled by the relaxation of selective pressures that constrained within-organism evolutionary processes in early life.
View Article and Find Full Text PDFFront Immunol
September 2025
Department of Hepatobiliary and Pancreatic Surgery, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China.
Pancreatic ductal adenocarcinoma (PDAC) remains a devastating malignancy characterized by profound lethality, aggressive local invasion, dismal prognosis, and significant resistance to existing therapies. Two critical biological features underpin the challenges in treating PDAC: extensive perineural invasion (PNI), the process by which cancer cells infiltrate and migrate along nerves, and a profoundly immunosuppressive, or "cold," tumor microenvironment (TME). PNI is not only a primary route for local tumor dissemination and recurrence but also a major contributor to the severe pain often experienced by patients.
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