Health Expect. 2025 Apr;28(2):e70260. doi: 10.1111/hex.70260.

ABSTRACT

BACKGROUND: Research about patient engagement for people with rare diseases has identified how the experiences of some members of the public are overlooked in relation to clinical trial design and trial participation. As part of a knowledge transfer partnership (KTP), the authors were granted access to patient insight reports about the needs of people with idiopathic pulmonary fibrosis (IPF), to inform clinical trial design and marketing strategy. These were contrasted with data from qualitative interviews, informed by and collected from people with IPF and the clinical staff who recruit them to trials.

OBJECTIVE: To identify patient and professional perspectives for IPF drug trials to create opportunities for innovation in patient engagement.

DESIGN: Ethnography. Qualitative researcher embedded in a pharmaceutical organisation.

SETTING AND PARTICIPANTS: International patient insight reports to inform a clinical trial protocol (n = 1) and marketing strategy (n = 6), including the experiences of over 100 patients with IPF. In the United Kingdom, interviews with patients with IPF (n = 32) and the staff who support them clinically and recruit them to trials of new medicines (n = 19) at one specialist interstitial lung disease (ILD) centre.

RESULTS: Methodological practices inherent in inpatient insight reports ensured the perspectives of some people with IPF were overlooked. Interviews with a more marginalised population of people with IPF, and the staff who support them, identified that some found trial information confusing, trial practices frustrating and the opportunities to engage in trial design absent.

DISCUSSION: Current pharmaceutical practices of working with contract research organisations and patient organisations exclude the perspectives of patients with IPF who do not engage with either. Trial recruitment information needs to be tailored to the needs of individuals, and trial processes need to enable a wider group of patients to participate.

CONCLUSIONS: People with IPF want the opportunity to participate in drug trials and trial science. However, methodological rigour and deliberative practices are required to enable a wider group of patients to have a stake in the design and conduct of drug trials for rare diseases. The challenge now is for regulators to mandate such inclusive practices and for pharmaceutical organisations to adopt them.

PATIENT OR PUBLIC CONTRIBUTION: A Patient Advisory Group (PAG) comprising six people with IPF gave input on the research protocol and then on the scope and content of the ongoing research. Two patients from international patient organisations served as a Steering Group (SG). Members of these groups provided their interpretations of the study findings and gave insight on their experiences in clinical design and participation.

PMID:40235185 | DOI:10.1111/hex.70260

JGH Open. 2025 Apr 15;9(4):e70157. doi: 10.1002/jgh3.70157. eCollection 2025 Apr.

ABSTRACT

CASE PRESENTATION: In Western Europe, intestinal tuberculosis is a rare differential diagnosis for Crohn's disease. In this report, we present a case of intestinal tuberculosis in a 59-year-old female initially suspected of Crohn's disease with persistent abdominal pain and diarrhea after appendectomy.

CONCLUSION: This case highlights the need for TB culture in patients with positive IGRA and suspected Crohn's disease.

PMID:40236937 | PMC:PMC11997620 | DOI:10.1002/jgh3.70157

Imeta. 2025 Mar 5;4(2):e70009. doi: 10.1002/imt2.70009. eCollection 2025 Apr.

ABSTRACT

Paralogous transcription factors (TFs) frequently recognize highly similar DNA motifs. Homodimerization can help distinguish them according to their different dimeric configurations. Here, by studying R2R3-MYB TFs, we show that homodimerization can also directly change the recognized DNA motifs to distinguish between similar TFs. By high-throughput SELEX, we profiled the specificity landscape for 40 R2R3-MYBs of subfamily VIII and curated 833 motif models. The dimeric models show that homodimeric binding has evoked specificity changes for AtMYBs. Focusing on AtMYB2 as an example, we show that homodimerization has modified its specificity and allowed it to recognize additional cis-regulatory sequences that are different from the closely related CCWAA-box AtMYBs and are unique among all AtMYBs. Genomic sites described by the modified dimeric specificities of AtMYB2 are conserved in evolution and involved in AtMYB2-specific transcriptional activation. Collectively, this study provides rich data on sequence preferences of VIII R2R3-MYBs and suggests an alternative mechanism that guides closely related TFs to respective cis-regulatory sites.

PMID:40236784 | PMC:PMC11995187 | DOI:10.1002/imt2.70009

Synth Syst Biotechnol. 2025 Mar 14;10(2):677-695. doi: 10.1016/j.synbio.2025.03.006. eCollection 2025 Jun.

ABSTRACT

DNA storage, characterized by its durability, data density, and cost-effectiveness, is a promising solution for managing the increasing data volumes in healthcare. This review explores state-of-the-art DNA storage technologies, and provides insights into designing a DNA storage system tailored for medical cold data. We anticipate that a practical approach for medical cold data storage will involve establishing regional, in vitro DNA storage centers that can serve multiple hospitals. The immediacy of DNA storage for medical data hinges on the development of novel, high-density, specialized coding methods. Established commercial techniques, such as DNA chemical synthesis and next-generation sequencing (NGS), along with mixed drying with alkaline salts and refined Polymerase Chain Reaction (PCR), potentially represent the optimal options for data writing, reading, storage, and accessing, respectively. Data security could be promised by the integration of traditional digital encryption and DNA steganography. Although breakthrough developments like artificial nucleotides and DNA nanostructures show potential, they remain in the laboratory research phase. In conclusion, DNA storage is a viable preservation strategy for medical cold data in the near future.

PMID:40235856 | PMC:PMC11999466 | DOI:10.1016/j.synbio.2025.03.006

Ecol Evol. 2025 Apr 15;15(4):e71262. doi: 10.1002/ece3.71262. eCollection 2025 Apr.

ABSTRACT

With the increasing interest in whole genome sequencing of eukaryotes, it is becoming evident that selecting the most suitable high molecular weight DNA extraction method is crucial for maximizing the benefits of long-read technologies. However, the DNA of many species cannot be processed immediately at the sampling site due to the remoteness of the location, necessitating tissue preservation that may affect DNA fragment size. This study aimed to identify the most suitable combination of four tissue preservation approaches and six DNA extraction methods to ensure high molecular weight DNA. A single Peltodoris atromaculata (Nudibranchia) specimen was sliced into ∼30 mg sub-samples, ensuring consistency across 24 preservation-extraction combinations processed in triplicates. Samples were either stored at 4°C, dried at room temperature, flash-frozen in liquid nitrogen, or preserved in ethanol and stored at -20°C. Afterward, they were processed using five commercially available kits specific for high molecular weight DNA extraction, as well as a custom DNA extraction protocol. Three aspects of DNA quality were evaluated: total yield, fragment size distribution, and availability of DNA for amplification. Most preservation-extraction combinations yielded optimal results in only some of the three DNA quality aspects. We identified six combinations suitable for long-read sequencing: a custom CTAB-based extraction protocol applied to frozen samples, Wizard (Promega) and Nanobind (PacBio) kits for both frozen and ethanol-preserved samples, and the ethanol preservation paired with Monarch (NEB) kits. The suitability of the six selected combinations was confirmed by PacBio sequencing, producing a total yield of 3.6 Gbp (3.2x estimated genome coverage). The results indicate that the success of high molecular weight DNA extractions is influenced by preservation methods. Although tested on nudibranchs, these findings are highly useful for genomic studies of other organisms, which may need to be preserved in remote locations before being transported to the laboratory for processing.

PMID:40235721 | PMC:PMC11997370 | DOI:10.1002/ece3.71262

Cureus. 2025 Mar 16;17(3):e80671. doi: 10.7759/cureus.80671. eCollection 2025 Mar.

ABSTRACT

We present the case of a 36-year-old man with a history of type 2 diabetes mellitus (T2DM) and prior plantar necrotizing fasciitis, who initially improved on semaglutide but later experienced weight gain and elevated hemoglobin A1C (HbA1c) levels. After switching to tirzepatide, he developed nausea, epigastric pain, and vomiting. Shortly after increasing the tirzepatide dosage, he presented to the emergency room with severe abdominal pain. Diagnostic imaging revealed an ulcer in the duodenal bulb with free air, indicating acute duodenal ulcer perforation. The patient underwent emergency surgery, and postoperative tests confirmed a Helicobacter pylori infection. He received eradication therapy and was discharged about two months later. This case highlights the potential risk of duodenal perforation associated with tirzepatide, particularly in patients with untreated Helicobacter pylori infection. The patient's worsening gastrointestinal symptoms and perforation after initiating tirzepatide suggest a potential drug-related effect, emphasizing the need for careful monitoring and further research into the mechanisms underlying gastrointestinal complications associated with tirzepatide.

PMID:40236372 | PMC:PMC11999657 | DOI:10.7759/cureus.80671

Res Sq [Preprint]. 2025 Apr 4:rs.3.rs-6271510. doi: 10.21203/rs.3.rs-6271510/v1.

ABSTRACT

The development of cholinergic neurotransmitter based cognitive enhancers for Alzheimer's disease and other neuropsychiatric disorders have focused recently on allosteric modulation of specific muscarinic acetylcholine receptor (mAChR) subtypes to reduce dose-limiting side-effects that have been the hallmark of earlier orthosteric mAChR agonists. VU0467319 (VU319) is an investigational positive allosteric modulator of the M 1 mAChR. A Phase 1 first-in-human study was conducted assessing safety and brain activity utilizing cognitive tasks and event-related potentials (ERPs) in single-ascending dose and food effect studies. VU319 was given orally to 52 healthy volunteers aged 18-55 years. The single ascending dose study tested 40 participants in five dose escalating cohorts (60, 120, 240, 400, 600 mg; 6 VU319/2 placebo per dose). The food effect study involved 12 participants, 10 VU319 (120 mg)/2 placebo. Exploratory cognitive and electrophysiological tasks were examined pre-dosing and at 5 hours post-dose. Tolerability was good with no observed dose limiting side effects throughout the full dose range tested. Drug exposure increased with dose in a less than dose-proportional manner with a half-life ranging from 36 to 43 hours. Absorption was increased with food. Exploratory cognitive/ERP testing showed evidence for drug-induced CNS activity on higher doses of VU319 compared to placebo. Single dose VU319 across five ascending cohorts appeared to have a favorable safety profile and a PK profile consistent with once daily dosing. Target engagement results suggest stimulation of the cholinergic system functioning in healthy adults following a single dose of VU319. These results provide a strong foundation for further studies of positive allosteric modulators of muscarinic M 1 receptors for potential cognitive or behavioral benefits.

PMID:40235479 | PMC:PMC11998771 | DOI:10.21203/rs.3.rs-6271510/v1

Orphanet J Rare Dis. 2025 Apr 15;20(1):180. doi: 10.1186/s13023-025-03695-3.

ABSTRACT

BACKGROUND: Fibrosing mediastinitis is a rare benign disease frequently complicated by pulmonary hypertension. A definitive diagnosis for fibrosing mediastinitis-associated pulmonary hypertension (FM-PH) and its etiologies necessitates mediastinal biopsy and subsequent pathological assessment. Endobronchial ultrasound (EBUS)-guided transbronchial mediastinal cryobiopsy is a recently developed technique that provides diagnostic advantages over standard needle biopsy, particularly in benign mediastinal disorders. Nevertheless, their safety and efficacy in diagnosing FM-PH remain elusive.

METHODS: We retrospectively studied patients with mediastinal lesion and pulmonary vascular compression who underwent both transbronchial needle aspiration and mediastinal cryobiopsy with EBUS guidance. Diagnostic yields of FM-PH and its etiologies, along with procedure-related adverse events, were analyzed. Immunohistochemical study was conducted to identify immunological properties of FM-PH.

RESULTS: Of the 529 patients with mediastinal lesions, 80 exhibited pulmonary vessel compression, including 10 who were ultimately diagnosed with FM-PH following mediastinal biopsy and right heart catheterization. Cryobiopsy showed a higher diagnostic yield for FM-PH compared to needle aspiration (100% versus 40%, p = 0.011). Disease etiologies included pneumoconiosis in 5 cases, tuberculosis in 3, and idiopathic FM-PH in the remaining 2. Cryobiopsy appeared to be superior to needle biopsy for etiological diagnosis, although this difference was not statistically significant (80% versus 60%, p = 0.628). Immunohistochemical analyses of cryosamples revealed mixed inflammatory infiltrates of B and T lymphocytes, as well as macrophages, surrounding or within FM-PH lesions. There was no significant bleeding or other complications.

CONCLUSION: Transbronchial mediastinal cryobiopsy might be a safe and effective diagnostic tool for FM-PH, offering valuable information for personalized treatment.

PMID:40234923 | DOI:10.1186/s13023-025-03695-3

Eur J Med Res. 2025 Apr 15;30(1):288. doi: 10.1186/s40001-025-02501-x.

ABSTRACT

BACKGROUND: The diagnosis of idiopathic pulmonary fibrosis (IPF) is complex, which requires lung biopsy, if necessary, and multidisciplinary discussions with specialists. Clinical diagnosis of the two ailments is particularly challenging due to the impact of interobserver variability. Several studies have endeavored to utilize image-based machine learning to diagnose IPF and its subtype of usual interstitial pneumonia (UIP). However, the diagnostic accuracy of this approach lacks evidence-based support.

OBJECTIVE: We conducted a systematic review and meta-analysis to explore the diagnostic efficiency of image-based machine learning (ML) for IPF.

DATA SOURCES AND METHODS: We comprehensively searched PubMed, Cochrane, Embase, and Web of Science databases up to August 24, 2024. During the meta-analysis, we carried out subgroup analyses by imaging source (computed radiography/computed tomography) and modeling type (deep learning/other) to evaluate its diagnostic performance for IPF.

RESULTS: The meta-analysis findings indicated that in the diagnosis of IPF, the C-index, sensitivity, and specificity of ML were 0.93 (95% CI 0.89-0.97), 0.79 (95% CI 0.73-0.83), and 0.84 (95% CI 0.79-0.88), respectively. The sensitivity of radiologists/clinicians in diagnosing IPF was 0.69 (95% CI 0.56-0.79), with a specificity of 0.93 (95% CI 0.74-0.98). For UIP diagnosis, the C-index of ML was 0.91 (95% CI 0.87-0.94), with a sensitivity of 0.92 (95% CI 0.80-0.97) and a specificity of 0.92 (95%CI 0.82-0.97). In contrast, the sensitivity of radiologists/clinicians in diagnosing UIP was 0.69 (95% CI 0.50-0.84), with a specificity of 0.90 (95% CI 0.82-0.94).

CONCLUSIONS: Image-based machine learning techniques demonstrate robust data processing and recognition capabilities, providing strong support for accurate diagnosis of idiopathic pulmonary fibrosis and usual interstitial pneumonia. Future multicenter large-scale studies are warranted to develop more intelligent evaluation tools to further enhance clinical diagnostic efficiency. Trial registration This study protocol was registered with PROSPERO (CRD42022383162).

PMID:40235000 | DOI:10.1186/s40001-025-02501-x

Thorax. 2025 Apr 15:thorax-2025-223299. doi: 10.1136/thorax-2025-223299. Online ahead of print.

NO ABSTRACT

PMID:40234006 | DOI:10.1136/thorax-2025-223299

Genome Biol. 2025 Apr 15;26(1):97. doi: 10.1186/s13059-025-03572-z.

ABSTRACT

Computational methods for assessing the likely impacts of mutations, known as variant effect predictors (VEPs), are widely used in the assessment and interpretation of human genetic variation, as well as in other applications like protein engineering. Many different VEPs have been released, and there is tremendous variability in their underlying algorithms, outputs, and the ways in which the methodologies and predictions are shared. This leads to considerable difficulties for users trying to navigate the selection and application of VEPs. Here, to address these issues, we provide guidelines and recommendations for the release of novel VEPs.

PMID:40234898 | DOI:10.1186/s13059-025-03572-z

Sci Rep. 2025 Apr 15;15(1):12884. doi: 10.1038/s41598-025-97366-9.

ABSTRACT

Bioluminescence imaging (BLI) is widely used in preclinical biomedical research for noninvasive tracking of cell populations and biochemical events in vivo. With recent improvements in BLI brightness from the engineering of bioluminescent enzymes (luciferases) and substrates (luciferins), optimizing luciferin formulations to maximize delivery and minimize toxicity becomes important, especially for marine coelenterazine-type luciferins with limited solubility. Here, we complete the characterization of a previously reported NanoLuc substrate, designated cephalofurimazine-9 (CFz9), and optimize its formulation with water-soluble excipients. We report a pH-controlled formulation of CFz9 enabling high-dose delivery to achieve peak brightness comparable to other furimazine analogs both inside and outside the brain while reducing toxicity. Thus, an optimized CFz9 formulation improves the performance and tolerability of whole-animal BLI with NanoLuc-based reporters.

PMID:40234651 | DOI:10.1038/s41598-025-97366-9

Mol Neurobiol. 2025 Apr 15. doi: 10.1007/s12035-025-04901-w. Online ahead of print.

ABSTRACT

GPAM, a key enzyme for lipid synthesis, is predominantly expressed in astrocytes (ASTs), where it facilitates lipid supply for myelin formation. Our previous studies identified GPAM as a novel causative gene for cerebral palsy (CP) and led to the development of a CP mouse model with GPAM deficiency (Gpam-/-). The model closely recapitulated the clinical phenotype of children with CP, due to the restricted proliferation of ASTs in the brain, reduced the amount of lipid, thinner brain white matter, and myelin dysplasia. The mammalian target of rapamycin (mTOR) pathway plays an important role in cell proliferation and lipid synthesis. Cytosolic arginine sensor (CASTOR1) interacts with GATOR2 to regulate mTOR complex 1 (mTORC1). Targeted degradation of CASTOR1 can activate the mTOR pathway. However, it remains unclear the involvement of mTOR pathway in neurological diseases such as CP. In this study, we demonstrated that the mTOR pathway was inhibited in Gpam-/- mice. Notably, CASTOR1 could regulate the activity of mTOR/S6K pathway, functioning as a negative upstream regulator. Furthermore, inhibition of CASTOR1 upregulated mTOR/S6K signaling, promoting astrocyte proliferation and myelination, which in turn enhanced motor function in the Gpam-/--induced CP mouse model. Collectively, these findings reveal the role of astrocytic mTOR in the pathogenesis of CP mice, broaden the therapeutic strategies, and provide a promising candidate target for CP treatment.

PMID:40234290 | DOI:10.1007/s12035-025-04901-w

Ann Oncol. 2025 Apr 14:S0923-7534(25)00131-0. doi: 10.1016/j.annonc.2025.03.020. Online ahead of print.

NO ABSTRACT

PMID:40234125 | DOI:10.1016/j.annonc.2025.03.020

Cell Rep Methods. 2025 Apr 8:101027. doi: 10.1016/j.crmeth.2025.101027. Online ahead of print.

ABSTRACT

Mitochondrial stress arises from a variety of sources, including mutations to mitochondrial DNA, the generation of reactive oxygen species, and an insufficient supply of oxygen or fuel. Mitochondrial stress induces a range of dedicated responses that repair damage and restore mitochondrial health. However, a systematic characterization of transcriptional and metabolic signatures induced by distinct types of mitochondrial stress is lacking. Here, we defined how primary human fibroblasts respond to a panel of mitochondrial inhibitors to trigger adaptive stress responses. Using metabolomic and transcriptomic analyses, we established integrated signatures of mitochondrial stress. We developed a tool, stress quantification using integrated datasets (SQUID), to deconvolute mitochondrial stress signatures from existing datasets. Using SQUID, we profiled mitochondrial stress in The Cancer Genome Atlas (TCGA) PanCancer Atlas, identifying a signature of pyruvate import deficiency in IDH1-mutant glioma. Thus, this study defines a tool to identify specific mitochondrial stress signatures, which may be applied to a range of systems.

PMID:40233762 | DOI:10.1016/j.crmeth.2025.101027

Drug Ther Bull. 2025 Apr 15:dtb-2024-000071. doi: 10.1136/dtb.2024.000071. Online ahead of print.

NO ABSTRACT

PMID:40234015 | DOI:10.1136/dtb.2024.000071

Sci Rep. 2025 Apr 15;15(1):12955. doi: 10.1038/s41598-025-97653-5.

ABSTRACT

Ionizing radiation induces DNA damage and impairs genomic integrity, leading to cell death and tissue injuries or carcinogenesis. Medical radiation protectors are essential and necessary. However, there are limited radioprotectors in clinics, which can't meet the growing demand for countering radiation emergencies. Traditional drug discovery approach has been proven expensive and risky. Computational drug repositioning provides an attractive strategy for radioprotector discovery. Here we constructed a systematic workflow to identify repositioning radioprotectors by comparison of biosimilarity between γ-ray and known medicines characterized by gene expression signatures from GEO and LINCS. Using enrichment scoring, medicines with negative scores were considered as candidates of revising or mitigating radiation injuries. Seven approved medicines were identified, and their targets enriched in steroid and estrogen metabolic, chemical carcinogenesis associated pathways. Lenalidomide, an approved medicine for multiple myeloma and anemia, was further verified as a promising potential radioprotector. It increases survival of mice after lethal doses of irradiation by alleviating bone marrow and intestinal injury in vivo, and inhibits apoptosis of cultured irradiated AHH- 1 and IEC- 6 cells in vitro. This study introduces rational drug repositioning to radiation medicine and provides viable candidates for radioprotective therapeutic regimens.

PMID:40234645 | DOI:10.1038/s41598-025-97653-5

Acta Pharmacol Sin. 2025 Apr 15. doi: 10.1038/s41401-025-01539-1. Online ahead of print.

ABSTRACT

Hyperlipidemia, a major risk factor for cardiovascular diseases, is associated with limitations in clinical lipid-lowering medications. Drug repurposing strategies expedite the research process and mitigate development costs, offering an innovative approach to drug discovery. This study employed systematic literature and guidelines review to compile a training set comprising 176 lipid-lowering drugs and 3254 non-lipid-lowering drugs. Multiple machine learning models were developed to predict the lipid-lowering potential of drugs. A multi-tiered validation strategy was implemented, encompassing large-scale retrospective clinical data analysis, standardized animal studies, molecular docking simulations and dynamics analyses. Through a comprehensive screening analysis utilizing machine learning, 29 FDA-approved drugs with lipid-lowering potential were identified. Clinical data analysis confirmed that four candidate drugs, with Argatroban as the representative, demonstrated lipid-lowering effects. In animal experiments, the candidate drugs significantly improved multiple blood lipid parameters. Molecular docking and dynamics simulations elucidated the binding patterns and stability of candidate drugs in interaction with related targets. We successfully identified multiple non-lipid-lowering drugs with lipid-lowering potential by integrating state-of-the-art machine learning techniques with multi-level validation methods, thereby providing new insights into lipid-lowering drugs, establishing a paradigm for AI-based drug repositioning research, and expanding the repertoire of lipid-lowering medications available to clinicians.

PMID:40234619 | DOI:10.1038/s41401-025-01539-1

Biomed Pharmacother. 2025 Apr 14;186:118047. doi: 10.1016/j.biopha.2025.118047. Online ahead of print.

ABSTRACT

In this study, we utilized the yeast two-hybrid system to screen for proteins interacting with USP24. Out of 250 such proteins, functional enrichment analysis using MetaCore™ indicated that 33 of them were involved in lung cancer progression. We then investigated gene expression and survival rates of these 33 proteins in lung cancer patients and cell lines through TCGA databases, Kaplan-Meier Plotter databases, and RNA-seq profile from A549/A549-T24 cells. By employing the patients' survival rate and gene expression profile of these 33 USP24-interacting proteins as gene signatures, we identified 10 potential drugs for inhibiting lung cancer progression or drug resistance via drug repurposing strategy using the Connectivity Map (CMap) database. Of these 10 drugs, six showed similar indicators in Clinical Trials, while the other four candidates (15-delta prostaglandin J2, Astemizole, Trifluoperazine, and 1,4-chrysenequinone) were chosen to evaluate their effect on re-sensitizing cytotoxicity of Taxol and Gefitinib in drug-resistant cancer cells. Experiments demonstrated that treatment with USP24-i-101 and Astemizole alone significantly inhibited drug resistance and re-sensitized the cytotoxicity of Taxol and Gefitinib in drug-resistant lung cancer cells. Notably, combination therapy with USP24-i-101and Astemizole re-sensitized the cytotoxicity of Taxol and Gefitinib in drug-resistant lung cancer, which could benefit in inhibiting drug resistance during cancer therapy.

PMID:40233501 | DOI:10.1016/j.biopha.2025.118047

Sci Data. 2025 Apr 15;12(1):634. doi: 10.1038/s41597-025-04922-z.

ABSTRACT

Distinctive facial phenotypes serve as crucial diagnostic markers for many rare genetic diseases. Although AI-driven image recognition achieves high diagnostic accuracy, it often fails to explain its predictions. In this study, we present the Facial phenotype-Gene-Disease Dataset (FGDD), an explainable dataset collected from 509 research publications. It contains 1,147 data records encompassing 197 disease-causing genes, 437 facial phenotypes, and 211 disease entities, with 689 records having disease labels. Each data record represents a patient group and includes demographic information, variation information, and phenotype information. Baseline and explainability validations conducted on FGDD confirmed the dataset's effectiveness. FGDD supports the training of diagnostic models for rare genetic diseases while delivering explainable results, and provides a foundation for exploring intricate connections between genes, diseases, and facial phenotypes.

PMID:40234471 | DOI:10.1038/s41597-025-04922-z