bims-curels 2026-08-16 papers

Issue of 2026–08–16
four papers selected by
Cure Mito Foundation

Front Digit Health. 2026 ;8 1833779

A call for principle-based acceptance of synthetic patients: establishing the AI-driven foundation for regulatory submissions.

Jordi Guitart.

The pharmaceutical industry stands at the precipice of an AI-driven data revolution, with synthetic patients emerging as a transformative tool to accelerate drug discovery and development while enhancing patient privacy. However, a critical regulatory gap persists: the absence of a standardized basis from leading regulatory bodies for accepting AI-generated patient populations as evidence in regulatory submissions. This manuscript addresses this void by proposing five foundational principles-Representativeness, Utility, Robustness, Privacy Preservation, and Transparency-anchored by the "Fit for Purpose" philosophy. We introduce the operational concept of a "Technical Validation Playbook" to facilitate the first wave of regulatory acceptances for synthetic patient data. We further outline actionable recommendations for regulatory agencies and pharmaceutical sponsors to advance the acceptance of synthetic patient populations through existing qualification and scientific advice mechanisms. By establishing a proactive, principle-based approach, this framework aims to catalyze regulatory-industry alignment and unlock the transformative potential of synthetic patients, particularly for populations with unmet medical needs such as rare diseases where traditional placebo-controlled trials face insurmountable ethical and recruitment challenges.

Keywords: GANs; VAEs; clinical trials; drug development; generative AI; rare diseases; regulatory framework; synthetic patient data

DOI: https://doi.org/10.3389/fdgth.2026.1833779

Cells. 2026 Aug 03. pii: 1403. [Epub ahead of print]15(15):

Exploring Heteroplasmic Variants in mtDNA: Insights from Single-Cell Transcriptomics.

Marco Barresi, Ivano Di Meo, Alessia Nasca, Eleonora Lamantea, Andrea Legati, Daniele Ghezzi.

Mitochondrial DNA (mtDNA) heteroplasmy, which is the coexistence of wild-type and mutant mtDNA variants within the same cell, plays a critical role in modulating cellular phenotypes, disease severity, and penetrance. Bulk RNA sequencing cannot detect cell-to-cell heteroplasmy variability, limiting our understanding of the pathological mechanisms of mtDNA variants. In this study, we leveraged single-cell RNA sequencing (scRNA-seq) combined with a robust bioinformatics pipeline to characterize mtDNA heteroplasmy. We employed four fibroblast lines from patients harboring heteroplasmic mtDNA pathogenic variants in genes encoding respiratory complex I subunits. While RNA heteroplasmy corresponded to DNA-based measurements at the bulk level, single-cell analysis uncovered a diverged distribution in three out of four lines: most cells had near-homoplasmic (wild-type or mutant) mtDNA, with few cells showing intermediate levels. Furthermore, we found that high mutation levels correlate with transcriptional profile changes, although these responses were highly sample-specific, suggesting that the nuclear background and cellular context critically influence mitochondrial dysfunction and compensatory mechanisms. Our findings highlight the potential of single-cell technologies to better understand the complex link between mtDNA genetic diversity and mitochondrial phenotypic variability and to study crucial aspects of mitochondrial biology and pathology, such as clonal dynamics, at single-cell resolution.

Keywords: heteroplasmy; mitochondrial DNA; mtDNA variant; single-cell transcriptomics

DOI: https://doi.org/10.3390/cells15151403

J Clin Ethics. 2026 ;37(3): 257-267

Understanding a Clinical Ethics Consult: Survey of Parents.

Vanessa N Madrigal, Kathryn Detwiler, Rebecca R Seltzer, Jennifer Shepard, William Sveen, Talia Bernhard Greenberg, Dörte Thorndike, Xiaobai Li, Renee D Boss, Miriam C Shapiro.

AbstractObjective: To explore parents' understanding of clinical ethics consults, what might influence their openness to an ethics consult in the future, and what they define as medical ethics.
STUDY DESIGN: Electronic survey of parents of children with complex medical conditions. Questions were adapted from a study of adult patients' and family members' experiences of ethical concerns in the healthcare setting. Respondents were also invited to participate in subsequent interviews.
RESULTS: We surveyed 218 parents and interviewed 28. Most respondents (63%) were not familiar with ethics consults and did not know how to request one (88%). For those reporting interest in a future ethics consult, knowing more about how ethics consults could help (71%) and a doctor's recommendation (58%) would most influence their interest. Hesitancy in speaking with an ethics consultant most often stemmed from worry that their child/family would not be understood (77%). Parents defined "medical ethics" as relating to serious medical conditions (67%), communication with the medical team (61%), and goals of care (57%). Interviews demonstrated generally consistent themes with the survey.
CONCLUSIONS: Pediatric ethics consultation is not a commonly recognized or utilized resource for families facing medical complexity and ethical challenges. More needs to be understood about how best to meet patient and family needs via ethics consults.

DOI: https://doi.org/10.1086/741894

Perspect Clin Res. 2026 Jul-Sep;17(3):17(3): 167-170

Quality of real-world registry studies.

Arun Bhatt.

Registry studies are types of real-world studies (RWS), which are used to generate clinical evidence regarding therapeutic use, potential benefits, or risks of a medical product in real-world medical practice, and to support regulatory decisions. RWS are conducted using real-world data (RWD), which are collected for patient care management, but not collected in compliance with good clinical practice standards for documentation. Hence, ensuring data quality, integrity, and reliability for studies using RWD is difficult. It is important to ensure the quality of research, data, and evidence during the planning and conduct of registry studies. This brief review discusses the elements critical to ensuring quality during planning and reporting of RWS.

Keywords: Data quality; evidence quality; registry; research quality

DOI: https://doi.org/10.4103/picr.picr_3_26