Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
Showing 3 appraisals
PloS one
Transcriptomic characterization of key psoriasis-associated genes based on single-cell RNA-seq and machine learning
BACKGROUND: Psoriasis is a multifaceted skin and systemic disorder driven by a complex interplay of genetic, immunological, and environmental factors. Genetic predisposition plays a pivotal role, with the IL-17/IL-23 immune axis recognized as a central pathogenic pathway. Ongoing research, however, continues to uncover additional critical drivers, cytokines, intracellular signaling networks, and potential therapeutic targets. METHODS: Single-cell RNA sequencing (scRNA-seq) datasets comprising both psoriatic and healthy samples were obtained from the Gene Expression Omnibus (GEO). Cell-type proportions were estimated using Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT), and weighted gene co-expression network analysis (WGCNA) was applied to explore correlations between cell types and gene signatures. Machine learning algorithms were subsequently employed to identify four psoriasis-associated key genes: DEFB4A, GJB2, SERPINB3, and SERPINB13. Their expression was validated in bulk RNA-seq datasets. Using scRNA-seq data, we further investigated the lesional regulatory roles of these genes and their associated pathway alterations, and we proposed targeted therapeutic strategies. RESULTS: A series of algorithms identified 271 hub genes significantly associated with psoriasis lesions and basal cells. Machine learning analysis refined this set to four key genes in psoriasis: DEFB4A, GJB2, SERPINB3, and SERPINB13. CONCLUSIONS: These four psoriasis-associated driver genes were upregulated in lesional skin. We also screened small-molecule compounds targeting these genes, offering potential therapeutic strategies.
14 July 2026
Read appraisal →BMJ supportive & palliative care
Time toxicity of patients with cancer enrolled in clinical trials: a systematic review and meta-analysis
PURPOSE: Time toxicity-the time patients spend receiving treatment, managing side effects, attending follow-ups and undergoing rehabilitation-is increasingly recognised as an important burden of cancer care. While time toxicity has been studied in routine clinical settings, it has rarely been quantified among patients with cancer enrolled in pharmacotherapy clinical trials. This systematic review aims to quantify time toxicity in this population. DESIGN: We searched Ovid MEDLINE, Embase and Cochrane CENTRAL from inception to 12 June 2025. Studies were included if they reported time toxicity among patients with cancer enrolled in clinical trials. Time toxicity was defined as calendar days with healthcare contact. Primary outcomes were (1) total days, (2) planned days and (3) unplanned days per month. Study quality was assessed using the Joanna Briggs Institute's (JBI) Checklist for Cohort Studies. RESULTS: Four retrospective studies reporting on an aggregate of 1809 patients were included. Two studies had low risk for bias and two had unclear risk of bias. Patients experienced time toxicity a mean of 7.6 days per month, with the highest burden in the first month of trial participation. Planned and unplanned days averaged 2.2 and 2.0 days per month, respectively. The ratio of planned to unplanned days remained consistent over time. CONCLUSIONS: Time toxicity is a substantial, under-recognised burden in cancer pharmacotherapy trials-approximately two times that experienced by non-participants. Its measurement and mitigation should be prioritised to improve patient-centred care, support shared decision-making and inform trial design, policy and consent processes. REGISTRATION: Study protocol preregistration: https://doi.org/10.17605/OSF.IO/BVY7C.
1 July 2026
Read appraisal →The Keio journal of medicine
Comparison of Clinical Development of Digital Therapeutics among Japan, the United States, and Germany
Digital therapeutics (DTx) have demonstrated promising potential as a novel therapeutic approach, with their clinical development gaining momentum. Comparison of DTx development between Japan, a relative newcomer, and Germany and the U.S., known for favorable circumstances, is a topic of interest. DTx developed in Japan as of November 2023 were identified on the Pharmaceuticals and Medical Devices Agency (PMDA) website and in the literature. Similar DTx available in the U.S. and Germany were identified in the databases maintained by the U.S. Food and Drug Administration (USFDA) and Federal Institute for Drugs and Medical Devices (BfArM). Data on their clinical trials and regulatory status were obtained from these databases and their respective national clinical trial registries. The data obtained were compared and analyzed. By November 2023, Japan had developed DTx, encompassing 11 therapeutic areas. Seven DTx had reached or completed the confirmatory study stage, whereas five DTx were in the exploratory phase. Twenty DTx in the therapeutic areas were selected from the U.S. and Germany. A total of 27 DTx were reviewed regarding the designs of confirmatory studies and regulatory actions taken. Trial designs demonstrated more similarities than differences across the countries and therapeutic areas. Placebo trial design-associated difficulties were conspicuous. Although regulatory actions to place DTx in the market differed across countries, they effectively ensured the efficacy and safety of DTx that were suitable for marketing considering the most current science. The regulatory measures in the three countries seem to have positively impacted DTx development.
27 June 2026
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