Search Results (53)

Background: Artificial Intelligence as a Medical Device (AIaMD) introduces regulatory, methodological, ethical, and clinical challenges that are not fully addressed by traditional device trial frameworks. Given rapidly evolving and jurisdiction-specific guidance, a consolidated mapping of trial design expectations and regulatory requirements is needed. Objective: To map regulatory requirements and clinical trial design approaches for AIaMD across major jurisdictions and to identify key methodological and implementation gaps relevant to adaptive/continuously learning systems. Methods: A scoping review was conducted in accordance with the PRISMA-ScR reporting guideline. Peer-reviewed literature (2017–2025) was searched in PubMed, Embase, Web of Science, and the Cochrane Library. Gray literature was identified from major regulators and policy bodies (FDA, EMA, MHRA, PMDA, WHO, CDSCO). Eligible records addressed AIaMD clinical evaluation, trial design, regulatory pathways, post-market surveillance, or reporting standards. Data were charted using a predefined extraction framework and synthesized descriptively with thematic analysis across regulatory, methodological, ethical, and clinical implementation domains. Results: Included sources demonstrate substantial heterogeneity in evidence expectations and AI-specific pathways across jurisdictions. Recurrent themes include the need for predefined change management, performance monitoring and drift controls, dataset representativeness and bias evaluation, transparency and versioning, cybersecurity, and real-world evidence integration. Reporting frameworks (SPIRIT-AI, CONSORT-AI, MI-CLAIM) are frequently cited as mechanisms to improve reproducibility and regulatory readiness. Conclusions: Evidence and regulatory expectations for AIaMD remain fragmented. Harmonization of terminology, trial design principles, and post-market governance—supported by standardized reporting—would improve clinical validity, safety assurance, and scalability across regions. This review has several limitations. As a scoping synthesis, it prioritizes breadth of coverage rather than quantitative meta-analysis. Included sources vary in methodological rigor and reporting detail, and evolving regulatory guidance may change rapidly over time. Nevertheless, integrating peer-reviewed and regulatory evidence provides a comprehensive overview of current expectations and emerging gaps. In conclusion, effective evaluation of AIaMD requires a shift from static, one-time validation toward continuous lifecycle oversight that integrates adaptive trial designs, transparent reporting standards, bias surveillance, and structured post-market monitoring. Regulatory heterogeneity currently poses significant barriers to multinational development; however, coordinated adoption of standardized evidence frameworks and collaborative governance mechanisms may reduce duplication while preserving patient safety. By translating methodological principles into operational guidance, this review aims to support regulators, sponsors, and clinical investigators in designing trials that are both scientifically rigorous and practically implementable for continuously learning systems. Full article

The etiology of idiopathic sudden sensorineural hearing loss (iSSNHL) remains unclear, and genome-wide genetic evidence is limited. We conducted a multicenter Japanese case–control genome-wide association study including 192 clinically defined iSSNHL cases and 15,302 controls aged ≥80 years without a history of hearing loss. After cross-platform SNP harmonization and imputation (Eagle/Minimac4), association testing was performed using dosage-based logistic regression in PLINK 2.0, adjusting for sex and principal components (PC1–PC10). Gene- and pathway-level analyses were conducted using MAGMA and the PANTHER overrepresentation test. Genomic inflation was modest (λ_GC = 1.04). Eight loci reached genome-wide significance (p < 5 × 10⁻⁸), led by FHIT, with additional loci near LHX2, TRMT1L, MEGF10, SPATS1, SAMD5, MYT1L, and ID4; 21 loci met the suggestive threshold (p < 1 × 10⁻⁶). MAGMA identified eight genes at FDR < 0.05 (FHIT, TRMT1L, MEGF10, RNF2, SWT1, VAMP1, TAPBPL, and C9orf3). These findings suggest that immune-inflammatory and cellular stress–homeostasis mechanisms may contribute to iSSNHL susceptibility and provide candidate loci for future replication and functional studies. Full article

The mechanisms underlying wound healing mediated by cannabinoid receptor 1 (CB1)—known for its neuromodulatory functions—remain incompletely understood. Therefore, we investigated the impact of activating CB1 using specific agonists, both in vitro and in vivo, with a focus on wound healing. In the in vitro study, fibroblasts were isolated and cultured from the dermis of human skin and treated with a CB1 agonist, 2-arachidonyl glyceryl ether (2-AGE). In the in vivo study, a mouse acute wound model was created using a skin biopsy punch and treated with the CB1 agonist arachidonoyl 2′-chloroethylamide (ACEA). The in vitro study revealed that 2-AGE increased cell proliferation and differentiation, upregulated the expression of alpha-smooth muscle actin (α-SMA), N-cadherin, and vimentin, and enhanced cell migration as well as the synthesis of type I and III collagen and fibronectin in normal human dermal fibroblasts. The CB1 antagonist AM251 abolished 2-AGE-induced expression of α-SMA, type I collagen, and fibronectin. In vivo, ACEA treatment accelerated wound closure, increased expression of α-SMA, type I collagen, and fibronectin, and ultimately increased epidermal and dermal thickness. Overall, these findings suggest that the activation of CB1 promotes wound healing and provides evidence for the therapeutic potential of CB1 agonists in wound treatment. Full article

The Yan goose (YE, Anser cygnoides) is a valuable indigenous poultry genetic resource, renowned for its superior meat quality and environmental adaptability. Despite its economic importance, the genetic basis underlying these adaptive traits remains unclear. In this study, we employed whole-genome resequencing (WGS) to perform high-throughput sequencing on a conserved population of 15 samples. Bioinformatic analyses were conducted to systematically evaluate the population’s genetic structure, and a genome-wide scan for selection signals related to economically significant traits was performed using the integrated haplotype score (iHS) method. An average of 4.43 million high-quality SNPs were identified, which were predominantly located in intergenic and intronic regions. Population structure analysis revealed a close genetic relationship within the conserved population of YE, with no significant lineage stratification observed. Pairwise sequentially Markovian coalescent (PSMC) analysis indicated that the YE underwent a severe genetic bottleneck during the Last Glacial Maximum (LGM), followed by gradual population recovery in the early Neolithic period. Genome-wide selection signal scanning identified multiple genomic regions under strong selection, annotating key genes associated with growth and development (e.g., GHRL, AKT1, and MAPK3), lipid deposition (e.g., PLPP4, SAMD8, and LPIN1), and disease resistance and stress resilience (e.g., TP53, STAT3). Functional enrichment analysis revealed significant enrichment of these genes in pathways related to glycerophospholipid metabolism (p < 0.01), purine metabolism (p < 0.01), and immune response (p < 0.01). This study not only provides a theoretical foundation for the scientific conservation of the YE germplasm resources but also offers valuable genomic resources for identifying functional genes underlying important economic traits and advancing molecular breeding strategies. Full article

Objective(s): To characterize the somatic mutational landscape of laryngeal squamous cell carcinoma (LSCC) using AACR Project GENIE data to identify potential biomarkers for tumor progression and guide precision therapy. Methods: Clinical and genomic data from 135 LSCC samples (primary and metastatic) were analyzed from the AACR Project GENIE database. Mutations were compared by tumor site and gender using chi-squared and Mann–Whitney U tests; co-occurrence and mutual-exclusivity analyses were performed. Results: TP53 mutations were most common (89.6%), followed by KMT2D (27.4%), FAT1 (20.7%), and NOTCH1 (20.7%). CDK8 mutations were enriched in females (p = 0.011) and ATP8B1 in males (p = 0.013). DMD mutations characterized primary tumors (p = 0.049), whereas ATP8B1 and SAMD9L were linked to metastases (p < 0.001). The cohort was 85.9% male and 71.5% White; 59.2% of samples were primary and 39.2% recurrent/metastatic. Co-occurrence analysis identified distinct molecular subtypes. The identification of distinct molecular subtypes and gender-specific mutations, such as CDK8 in females and ATP8B1 in males, suggests potential avenues for tailored therapeutic interventions. Conclusions: LSCC exhibits marked genetic heterogeneity dominated by TP53 alterations. ATP8B1 and SAMD9L mutations may mark metastatic disease, and gender-specific mutations suggest avenues for personalized therapy. These insights support development of targeted strategies, including immunotherapies such as pembrolizumab in TP53-altered tumors. These insights into the genomic heterogeneity of LSCC lay the groundwork for developing targeted therapeutic strategies and patient stratification, ultimately advancing a personalized medicine approach to this disease. Full article

Avian reovirus (ARV) is an important pathogen of poultry, yet the molecular responses to ARV across cell types remain unknown. The present study explores the differential transcriptomic responses to ARV S1133 infection in three cell types, i.e., chicken embryo kidney (CEK), chicken embryo liver (CELi), and macrophage-derived cells (HD11) at 6, 12, and 24 h post-inoculation (hpi). CELi cells exhibited the highest viral replication rates at all timepoints, with maximal titer observed at 24 hpi, whereas HD11 cells showed limited viral replication but extensive host transcriptional activity. Differential gene expression analysis revealed that macrophage-derived (HD11) cells, despite the lower viral load, presented the most pronounced transcriptional changes. CEK cells demonstrated a unique activation of immune-related pathways, specifically those related to lymphocyte chemotaxis and type II interferon response. CELi cells showed upregulation of expression of genes involved in defense against viruses. Protein–protein interaction (PPI) analysis identified key antiviral genes, including IFI6, OASL, RSAD2, SAMD9L, and MX1, as central nodes. In CELi, significant alternative splicing events were observed in transcripts of several genes, including those implicated in immunity. Taken together, results indicate that inoculation of ARV triggered cell-type and time-dependent viral replication and stimulated transcriptional activity linked with unique but functionally interconnected pathways. Full article

Background/Objectives: Systemic sclerosis (SSc) is a heterogeneous connective tissue disease characterized by immune dysregulation, vasculopathy, and fibrosis. Objectives: To evaluate the genetic architecture and autoantibody profile in a Kazakh cohort of patients with SSc. Methods: A total of 26 Kazakh patients with diffuse SSc were examined for disease activity and organ impairment using EScSG and the modified Rodnan skin score (mRSS). Eighteen healthy volunteers were enrolled in the control group. Antinuclear factor (ANF) was estimated on HEp-2 cells, while antibodies to Scl-70, CENP-B, U1-snRNP, SS-A/Ro52, SS-A/Ro60, Sm/RNP, Sm, SS-B, Rib-P0, and nucleosomes were determined by immunoblotting. The level of IL-6 cytokine was detected using ELISA. To investigate the genetic basis of SSc in Kazakh patients, a custom AmpliSeq panel including targeting immune/fibrosis pathways and 120 genes was used on the Ion Proton sequencer. The statistical analysis of categorical variables was conducted using Fisher’s exact test and Chi-square (χ²) test. Results: The examination of SSc patients (mRSS 16 ± 7.2; EScSG 3.54 ± 2.18) revealed a broad range of antibodies to Scl-70, CENP-B, SS-A/Ro60, SS-A/Ro52, U1-snRNP, and RNP/Sm, which were undetectable in the control group. Genetic analysis identified multiple variants across immune regulatory genes, including likely pathogenic changes in SAMD9L, REL, IL6ST, TNFAIP3, ITGA2, ABCC2, AIRE, IL6R, AFF3, and TREX1. Variants of uncertain clinical significance were detected in LY96, IRAK1, RBPJ, IL6ST, ITGA2, AIRE, IL6R, JAZF1, IKZF3, IL18, IL12B, PRKCQ, PXK, and DNASE1L3. Novel variants at the following genomic coordinates were identified and have not been previously reported in association with SSc: LY96 (chr8:74922341 CT/C), PTPN22 (chr1:114381166 CT/C), IRAK1 (indels at chrX:153278833), and SAMD9L (chr7:92761606 GT/G; chr7:92764981 T/TT). Conclusions: The first immunogenetic investigation of SSc in Kazakhstan revealed a polygenic architecture involving immune signalling pathways that partially overlap with international cohorts while exhibiting region-specific variation. Although the limited sample size and lack of functional validation constrain the interpretability of the findings, the results provide a framework for larger research to confirm the pathogenic mechanisms and establish clinical relevance. Full article

The Sterile alpha motif domain-containing protein 4 (SAMD4) family consists of two evolutionarily conserved and highly homologous RNA-binding proteins, SAMD4A and SAMD4B. Previous studies have established SAMD4A as a tumor suppressor that is downregulated in breast cancer, while the function of SAMD4B in tumorigenesis remains poorly defined. In this study, we observed that SAMD4B expression is upregulated in breast cancer. Functional assays demonstrated that SAMD4B facilitated breast cancer cell proliferation, migration, and invasion by inducing epithelial–mesenchymal transition (EMT). Furthermore, SAMD4B accelerated G1-to-S phase cell cycle progression by modulating p53 expression, collectively supporting an oncogenic function of SAMD4B in breast cancer. Mechanistically, we found that SAMD4B enhanced TCF/LEF transcriptional activity and upregulated the expression of β-catenin, Cyclin D1, c-Myc, and Axin2. Further investigations confirmed that SAMD4B activated the Wnt/β-catenin pathway by stabilizing β-catenin mRNA and increasing β-catenin protein expression level. Importantly, treatment with XAV-939, a specific Wnt/β-catenin pathway inhibitor, abrogated the pro-oncogenic effects of SAMD4B overexpression, including Wnt/β-catenin pathway activation, enhanced proliferation, and increased metastatic capacity. These results confirm that SAMD4B promotes the malignant phenotypes of breast cancer cells in a manner dependent on the Wnt/β-catenin pathway. In summary, our findings clarify that SAMD4B exerts an oncogenic role in breast cancer progression by activating the Wnt/β-catenin pathway. These data identify SAMD4B as a potential therapeutic target in breast cancer, although further in vivo investigations are required to validate its clinical relevance. Full article

Complete or partial deletions of chromosome 7 (-7/del7q) represent the most frequent chromosomal abnormalities observed in myeloid neoplasms (MNs) and are associated with a poor prognosis. -7/del7q is observed in 10–15% of adult patients with myelodysplasia (MDS) or with acute myeloid leukemia (AML). The occurrence of -7/del7q is particularly frequent in pediatric MDS, often associated with germline mutations of GATA2 or SAMD9/SAMD9L genes. The disease biology of -7/del7q and the genes driving leukemic development have not been completely elucidated, but the haploinsufficiency of tumor suppressor genes located in chromosome 7 deleted regions seems to play a relevant role. The response to standard treatments based either on chemotherapy or hypomethylating agents plus Venetoclax is limited. No approved targeted therapies exist for patients with -7/del7q; however, some recent studies have discovered some vulnerabilities of these myeloid neoplasms than can be efficiently targeted. Full article

Systemic sclerosis (SSc) is an autoimmune connective tissue disorder characterized by vascular abnormalities, immune dysfunction, and progressive fibrosis. One of the most common manifestations of SSc is interstitial lung disease (ILD), known by a progressive course leading to significant morbidity and mortality. Aim: to investigate autoantibodies, cytokines, and genetic markers in SSc-ILD through a systematic review and analysis of a Kazakh cohort of SSc-ILD patients. Methods: A PubMed search over the past 10 years was performed with “SSc-ILD”, “autoantibodies”, “cytokines”, and “genes”. Thirty patients with SSc were assessed for lung involvement, EScSG score, and modified Rodnan skin score. IL-6 was measured by ELISA, antinuclear factor on HEp-2 cells by indirect immunofluorescence, and specific autoantibodies by immunoblotting. Genetic analysis was performed using a 120-gene AmpliSeq panel on the Ion Proton platform. Results: The literature review identified 361 articles, 26 addressed autoantibodies, 20 genetic variants, and 12 cytokine profiles. Elevated levels of IL-6, TGF-β, IL-33, and TNF-α were linked to SSc. Based on the results of the systemic review, we created a preliminary immunogenic panel for SSc-ILD with following analysis in Kazakh patients with SSc (n = 30). Fourteen of them (46.7%) demonstrated signs of ILD and/or lung hypertension, with frequent detection of antibodies such as Scl-70, U1-snRNP, SS-A, and genetic variants in SAMD9L, REL, IRAK1, LY96, IL6R, ITGA2B, AIRE, TREX1, and CD40 genes. Conclusions: Current research confirmed the presence of the broad range of autoantibodies and variations in IRAK1, TNFAIP3, SAMD9L, REL, IRAK1, LY96, IL6R, ITGA2B, AIRE, TREX1, CD40 genes in of Kazakhstani cohort of SSc-ILD patients. Full article

Myxoma virus (MYXV), a rabbit-specific poxvirus and non-pathogenic in humans and mice, is an excellent candidate oncolytic virus for cancer therapy. MYXV also has immunotherapeutic benefits. In ovarian cancer (OC), immunosuppressive tumor-associated macrophages (TAMs) are key to inhibiting antitumor immunity while hindering therapeutic benefit by chemotherapy and dendritic cell (DC) vaccine. Because MYXV favors binding/entry of macrophages/monocytes, we examined the therapeutic potential of MYXV against TAMs. We found previously that a replication-defective MYXV with targeted deletion of an essential gene, M062R, designated ΔM062R MYXV, activated both the host DNA sensing pathway and the SAMD9 pathway. Treatment with ΔM062R confers therapeutic benefit comparable to that of wild-type replicating MYXV in preclinical models. Here we found that ΔM062R MYXV, when integrated with cisplatin and DC immunotherapy, further improved treatment benefit, likely through promoting tumor antigen-specific T cell function. Moreover, we also tested ΔM062R MYXV in targeting human immunosuppressive TAMs from OC patient ascites in a co-culture system. We found that ΔM062R treatment subverted the immunosuppressive properties of TAMs and elevated the avidity of cytokine production in tumor antigen-specific CD4⁺ T cells. Overall, ΔM062R presents a promising immunotherapeutic platform as a beneficial adjuvant to chemotherapy and DC vaccine. Full article

This study aimed to identify genetic variants using a customized next-generation sequencing (NGS) panel for pediatric myelodysplastic syndrome (pMDS) and to explore their associations with cytogenetic and clinical characteristics. Cytogenetic analyses were conducted using G-banding and fluorescence in situ hybridization. NGS was performed with the Ion Torrent Personal Genome Machine for the following genes: GATA2, RUNX1, CEBPA, ANKRD26, ETV6, SAMD9, SAMD9L, PTPN11, NRAS, SETBP1, DDX41, TP53, FLT3, SRP72, and JAK3. Analyses were performed with Ion Reporter 5.20.8.0 software. Genetic variants were classified using the dbSNP, 1000 Genomes, COSMIC, and Varsome databases. We analyzed 25 cases of pMDS; 15 presented abnormal karyotypes, and 19 showed genetic variants. Among the 29 variants identified across 12/15 genes, 27% were pathogenic and 14% were likely pathogenic, with NRAS and GATA2 most frequently associated with disease progression. A new somatic variant of uncertain significance in SETBP1 was detected in seven patients showing heterogeneous clinical outcomes. Genetic variants were found in 7/10 patients with normal karyotypes, indicating that submicroscopic alterations can shed light on disease biology. Our results highlight the critical role of a targeted NGS panel in identifying molecular alterations associated with pMDS pathogenesis, thereby enhancing diagnostic precision, prognosis, and aiding in treatment selection. Full article

This study aimed to investigate population genetic differences related to reproductive traits between Duroc and Yorkshire (Dutch Large White) pigs using two approaches: linear mixed models that dissect additive and dominant effects, and selective sweep analysis. (1) Methods: Genome-wide single-nucleotide polymorphism (SNP) data of 3917 Duroc and 3217 Yorkshire pigs were analyzed. The first principal component (PC1) was used as a simulated phenotype to capture population-level variance. Additive and dominant genetic effects were partitioned and evaluated by using the combination of the linear mixed models (LMM) and ADDO’s algorithm (LMM + ADDO). In parallel, selective sweep signals were detected using fixation index (F_ST) and nucleotide diversity (θ_π) analyses. A comparative assessment was then conducted between the LMM + ADDO and the selective sweep analysis results. Significant loci were annotated using quantitative trait loci (QTL) databases and the Ensembl genome browser. (2) Results: There are 39040 SNPs retained after quality control. Using the LMM + ADDO framework with PC1 as a simulated phenotype, a total of 632 significant SNPs and 184 candidate genes were identified. Notably, 587 SNPs and 171 genes were uniquely detected by the LMM + ADDO method and not among loci detected by the top 5% of F_ST and θ_π values. Key candidate genes associated with litter size included HSPG2, KAT6B, SAMD8, and LRMDA, while DLGAP1, MYOM1, and VTI1A were associated with teat number traits. (3) Conclusions: This study demonstrates the power of integrating additive and dominant effect modeling with population genetics approaches for the detection of genomic regions under selection. The findings provide novel insights into the genetic architecture of reproductive traits in pigs and have practical implications for understanding the inheritance of complex traits. Full article

Background/Objectives: Artificial intelligence is revolutionizing healthcare. In the recent years, AI tools have been incorporated by medical specialties that heavily rely on imaging techniques to aid in the diagnosis, management, and monitoring of a wide array of clinical conditions. Methods: Thoracic surgery is not an exception: AI is becoming a reality, although it is only the beginning. AI-based tools can be employed in medicine, and by extracting useful information from big data, they allow for the early diagnosis of diseases like lung cancer. Diagnostic imaging is the most promising clinical application of AI in medicine. Results: As for other specialties, ethical issues represent a challenge in thoracic surgery and must be addressed before introducing these applications. Data protection and biases, privacy, ‘the black box’ problem (explainability), and responsibility are some challenges that AI must supplant. Conclusions: In this review, the authors aim to highlight the importance of AI in thoracic surgery. AI applications, future directions, and clinical benefits and challenges, particularly in this area, will be addressed, highlighting solutions to successfully incorporate AI into healthcare protocols. Full article

The evaluation of external pelvimetry measurements and the genetic factors influencing them is essential for improving morphological characteristics and reproductive performance in cattle. This study represents the first comprehensive analysis of the association between single nucleotide polymorphisms (SNPs) and external pelvimetry traits in Romanian Simmental cattle, a breed recognized for its distinctive pelvic morphology. The relationship between single-nucleotide polymorphisms (SNPs) and external pelvimetry traits—including croup height (CH), buttock height (BH), croup width (CW), rump angle (RA), and croup length (CL)—was examined in Simmental cows. From an initial set of 110 SNPs, 33 markers were retained after applying quality control filters, including a minor allele frequency (MAF) greater than 0.05 and Hardy–Weinberg equilibrium. These SNPs, located on multiple chromosomes, were identified within intronic, exonic, or regulatory regions of relevant genes such as CLSTN2, DPYD, FBXL7, FBXL13, SEMA6A, RUNX2, FSTL4, DST, DCBLD2, FRMD6, CAV2.3, ABL2, SH3BP4, RSBN1L,and SAMD12, suggesting that these genetic variants may influence the development and morphology of the pelvic bones. Statistical analysis revealed significant relationships between certain allele variants and croup measurements, highlighting that the presence of alternative alleles can modify their morphological traits. Notably, the G allele in CLSTN2 reduced croup height by 5.74 cm (p = 0.0227), while the T allele in RUNX2 decreased rump angle by 4.49° (p = 0.0119). Full article