Search Results (6,641)

Milk beer, a modern Chinese dairy beverage, is usually fermented by the co-culture of lactic acid bacteria (LAB) and Kluyveromyces marxianus (K. marxianus), with the latter known for its ability to produce aroma compounds. However, the accumulation of lactic acid produced by LAB can inhibit the growth of K. marxianus, which inevitably hinders the diversity and intensity of flavor compounds in milk beer. In this study, adaptive laboratory evolution (ALE) was applied to the parental strain Kluyveromyces marxianus CICC1953 (Km-P) under different concentrations of lactic acid to obtain an evolved strain Km-ALE-X20 with enhanced acid tolerance and increased titer of phenylethyl alcohol, which has a floral, rose-like aroma. Km-ALE-X20 demonstrated a 16-fold increase in OD₆₀₀ and a 28-fold increase in phenylethyl alcohol production compared with Km-P in chemically defined medium (CDM) containing 20 g/L lactic acid. Comparative genomics analysis suggested that mutated genes CTA1, TSL1, ERG2 were related to enhanced acid tolerance, while ARO8, ARO9, FKS2 were related to increased production of aroma compounds. Furthermore, Km-ALE-X20-fermented milk beer showed 33.87% and 32.43% higher production in alcohol and ester compounds than that of Km-P-fermented milk beer. Interestingly, sensory analysis showed that while Km-ALE-X20-fermented milk beer had higher sensory scores for rose and fruity aroma attributes, Km-P-fermented milk beer possessed a more balanced aroma profile. This paper highlights the first application of ALE to enhance the signature rose aroma of K. marxianus-fermented milk beer and provides an efficient framework for ALE-based breeding of aroma-producing food microorganisms. Full article

Acrolein, a highly reactive environmental toxicant widely present in urban air and tobacco smoke, has been implicated in the development of multiple malignancies. In oral tissues, chronic acrolein exposure induces oxidative stress, inflammation, and genetic mutations, all of which are closely linked to the development of oral squamous cell carcinoma (OSCC). Although accumulating evidence indicates a strong association between acrolein exposure and OSCC, its prognostic significance remains poorly understood. In this study, we analyzed transcriptome data to identify differentially expressed genes (DEGs) between tumor and adjacent normal tissues, and screened acrolein-related candidates by intersecting DEGs with previously identified acrolein-associated gene sets. Functional alterations of these genes were assessed using Gene Set Variation Analysis (GSVA), and a protein–protein interaction (PPI) network was constructed to identify key regulatory genes. A prognostic model was developed using Support Vector Machine–Recursive Feature Elimination (SVM-RFE) combined with LASSO-Cox regression and validated in an independent external cohort. Among the acrolein-related DEGs, four key genes (PLK1, AURKA, CTLA4, and PPARG) were ultimately selected for model construction. Kaplan–Meier analysis showed significantly worse overall survival in the high-risk group (p < 0.0001). Receiver operating characteristic (ROC) curve analysis further confirmed the strong predictive performance of the model, with area under the curve (AUC) values of 0.72 at 1 year, 0.72 at 3 years, and 0.75 at 5 years. Furthermore, the high risk score was significantly correlated with a ‘cold’ immune microenviroment, suggesting that acrolein-related genes may modulate the tumor immune microenvironment. Collectively, these findings highlight the role of acrolein in OSCC progression, suggesting the importance of reducing acrolein exposure for cancer prevention and public health, and call for increased attention to the relationship between environmental toxicants and disease initiation, providing a scientific basis for public health interventions and cancer prevention strategies. Full article

Backgroundand Objectives: Cervical adenocarcinoma (CAC) is a histologically distinct subtype of cervical cancer with a rising incidence in many regions. While the roles of key driver mutations are known, a comprehensive understanding of its genomic landscape, particularly variations across different populations and tumor stages, remains incomplete. This study aims to characterize the somatic genomic landscape of CAC by identifying recurrent mutations, copy number alterations (CNAs), and patterns of co-occurrence, with a focus on variations across racial groups and between primary and metastatic tumors. Materials and Methods: We conducted a comprehensive genomic analysis of 102 tumor samples from 99 patients diagnosed with cervical adenocarcinoma using data from the American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) database. Results: The most frequently mutated genes were PIK3CA (25.5%), TP53 (21.6%), ARID1A (20.6%), and KRAS (16.7%). Significant amplification of ERBB2 was also observed (n = 3; 4.83%). Our analysis revealed notable genomic disparities across racial groups, with TP53 mutations being significantly more frequent in White patients compared to Asian and Black patients (p = 0.0236). Furthermore, we identified significant co-occurrence between mutations in KRAS and MSH2 (p = 0.011) as well as ATM and STK11 (p = 0.037). In comparing tumor types, mutations in BCL6 were found to be significantly enriched in metastatic samples. Conclusions: This study validates the primary drivers of cervical adenocarcinoma and reveals novel findings, including notable racial disparities in TP53 mutation frequency and unique patterns of co-occurring mutations. These findings highlight the genomic heterogeneity of the disease and suggest that ancestry and tumor evolution may influence its molecular pathogenesis, offering potential avenues for the development of targeted therapies and personalized biomarkers. Full article

Bioactive natural products (NPs) may play a critical role in cancer progression by targeting nucleic acids and a wide array of proteins, including enzymes. Furthermore, a large number of derivatives (NPDs), including semi-synthetic products and pharmacophores from NPs, have been developed to enhance the solubility and stability of NPs. Acute myeloid leukemia (AML) is a poor-prognosis hematologic malignancy characterized by the clonal accumulation in the blood and bone marrow of myeloid progenitors with high proliferative capacity, survival and propagation abilities. A number of potential pathways and targets have been identified for development in AML, and include, but are not limited to, Fms-like tyrosine kinase 3 (FLT3) and isocitrate dehydrogenases resulting from genetic mutations, BCL2 family members, various signaling kinases and histone deacetylases, as well as tumor-associated antigens (such as CD13, CD33, P-gp). By targeting nucleic acids, FLT3 or CD33, several FDA-approved NPs and NPDs (i.e., cytarabine, anthracyclines, midostaurin, melphalan and calicheamicin linked to anti-CD33) are the major agents of upfront treatment of AML. However, the effective treatment of the disease remains challenging, in part due to the heterogeneity of the disease but also to the involvement of the bone marrow microenvironment and the immune system in favoring leukemic stem cell persistence. This review summarizes the current state of the art, and provides a summary of selected NPs/NPDs which are either entering or have been investigated in preclinical and clinical trials, alone or in combination with current chemotherapy. With multifaceted actions, these biomolecules may target all hallmarks of AML, including multidrug resistance and deregulated metabolism. Full article

Human zinc finger Ran-binding protein 3 (ZRANB3) is crucial for DNA damage tolerance (DDT), as it prevents excessive damage, restores fork progression, and ultimately maintains genome stability. This unique and ancient architecture mainly exerts its function during replication fork reversal (RFR) and within the p53/Polι axis; thus, ZRANB3 is considered a tumour suppressor. However, possible additional roles in DNA synthesis and cell metabolism have been proposed. In tumour cells, ZRANB3 gene expression is deregulated, a condition that is frequently associated with poor survival and adverse clinical outcomes. ZRANB3 can be altered by functional mutations, gene copy number alterations, and a combination of the two. Although its mRNA levels typically correlate with p53 expression, this correlation breaks down in the context of p53 mutations and high proliferative activity. This comprehensive review integrates the currently available yet fragmented literature on ZRANB3, both at the gene and protein levels, examines its regulation in cancer development, and discusses the evidence supporting its role as a tumour suppressor and prognostic biomarker. Full article

Background: Progressive familial intrahepatic cholestasis (PFIC) describes a group of genetically heterogeneous disorders. Several mutations in the ATP-Binding Cassette Subfamily B Member 4 (ABCB4) gene have been confirmed to cause reduced phosphatidylcholine levels in bile, leading to a deficiency of biliary vesicles and instability of mixed in micelles. The disease spectrum ranges from PFIC type 3 (PFIC3) to milder conditions. Herein, we present a rare case of PFIC3 in a young woman, emphasizing the importance of early detection and management. Methods: The patient was diagnosed using next-generation sequencing, with genetic testing and analysis performed by the Chengdu Hua Chuang Testing Institute. Variant pathogenicity was evaluated according to the American College of Medical Genetics and Genomics guidelines and classified into five categories: pathogenic, likely pathogenic, uncertain significance, likely benign, and benign. Nomenclature was assigned following the Human Genome Variation Society standards. Results: Contrast-enhanced abdominal computed tomography demonstrated liver cirrhosis with marked splenomegaly. Histological examination of liver biopsy specimens using hematoxylin and eosin and Masson staining further confirmed cirrhotic changes. Genetic testing was subsequently performed and revealed a likely pathogenic variant, c.2757T > A (p. Tyr919Ter), in exon 22 of the ABCB4 gene, which was also detected in the patient’s mother but absent in her father. Finally, PFIC3 was diagnosed. Following initiation of ursodeoxycholic acid therapy, the patient showed moderate improvement in liver function tests, underscoring a clinical case with therapeutic implications. Conclusions: Molecular genetic analyses of ABCB4 are essential for the accurate diagnosis of PFIC3. Clinicians should consider cholestatic liver diseases, particularly PFIC, as a differential diagnosis in cases of liver cirrhosis with unknown etiology, especially in young patients who lack prior symptoms or a family history of liver disease. Full article

Background: Molecular classification has reshaped prognostication and treatment in endometrial carcinoma (EC). However, real-world evidence from Asian populations remains scarce. This study evaluated clinicopathologic characteristics and survival outcomes across molecular subtypes of EC in a Thai tertiary care center. Methods: This retrospective cohort included patients with histologically confirmed EC who underwent primary surgery at Chiang Mai University Hospital between 2015 and 2023, and had at least one investigation for molecular classification, including immunohistochemistry (IHC) for mismatch repair (MMR) proteins and p53, as well as POLE sequencing using the Idylla™ POLE–POLD1 Mutation Assay with confirmatory Sanger sequencing. Final molecular subtype assignment followed established hierarchical algorithms. Clinicopathologic variables were analyzed using Chi-square and logistic regression. Progression-free survival (PFS) and overall survival (OS) were estimated with Kaplan–Meier and compared using the log-rank test. Results: Among 803 EC cases diagnosed during the study period, 184 met the inclusion criteria. Of 184 patients, molecular subtypes were classified as POLE-mutated in 2.2%, dMMR in 38.6%, p53-abnormal (p53-abn) in 45.1% and NSMP (1.6%). dMMR tumors occurred predominantly in older women and exhibited mainly endometrioid histology, whereas p53-abn tumors were largely non-endometrioid and high-risk in the vast majority. In multivariate analysis, histologic type was the only independent predictor of both MMR deficiency (adjusted OR = 15.22; 95% CI 4.99–46.37; p < 0.001) and p53 abnormality (adjusted OR = 79.42; 95% CI 10.60–595.05; p = 0.003). Survival outcomes varied by molecular class: POLE-mutated tumors had excellent prognosis with no recurrence or death, dMMR tumors had intermediate outcomes, and p53-abn tumors showed the poorest PFS and OS. Overall survival differed significantly among subtypes. Conclusions: Molecular classification provides strong prognostic discrimination in EC, even with selective testing. MMR and p53 IHC serve as practical frontline tools, while POLE sequencing should be prioritized for intermediate- and high-risk endometrioid tumors. Expanded molecular testing in Asian populations is essential to refine risk stratification and optimize individualized management. Full article

The Na⁺/K⁺/2Cl⁻ cotransporter (NKCC) gene encodes a critical membrane transporter involved in cellular ion homeostasis and plays a pivotal role in osmoregulation and salinity adaptation in aquatic organisms. This study identified and validated SNP markers in the NKCC gene associated with low-salinity tolerance in Scylla paramamosain. Four SNPs (g.196C>A, g.8374T>A, g.8385T>A and g.91143T>A) were screened and genotyped in low-salinity tolerant and intolerant groups. Association analysis revealed that mutant genotypes at all four sites were significantly enriched in the tolerant group (p <0.05), with the values of odds ratios (OR) greater than 1. The tolerant group exhibited significantly higher genetic diversity than the intolerant group. Haplotype analysis showed the wild CTTT haplotype dominated in the intolerant group, while mutant-containing haplotypes were significantly elevated in the tolerant group. A positive correlation was observed between the mutant and NKCC expression. Functional validation by qRT-PCR demonstrated that mutant allele carriers exhibited significantly higher NKCC mRNA expression levels than the wild-type carriers. Moreover, the expression level of homozygous mutations is significantly higher than that of heterozygous mutations. These validated SNPs could provide effective molecular markers for marker-assisted selection breeding of low-salinity tolerant S. paramamosain strains, offering important theoretical and practical implications for sustainable aquaculture development. Full article

Monogenic forms of severe early-onset obesity often involve genetic disruptions in the hypothalamic leptin-melanocortin pathway. Pathogenic variants in the SIM1 gene, a key transcription factor required for the development of the paraventricular nucleus, are a known cause of Prader–Willi-like syndrome, characterized by hyperphagia, severe obesity, and developmental delay. We performed targeted next-generation sequencing of 52 obesity-associated genes on a cohort of pediatric patients with severe early-onset obesity. Identified variants were analyzed for population frequency and predicted pathogenicity using in silico tools. The structural impact of the novel missense variants was assessed using protein domain modeling with AlphaFold3. We identified five rare SIM1 variants in eleven patients. Four were heterozygous nonsynonymous variants: one frameshift in the bHLH domain (p.Ser18Ter), one frameshift in the Per-ARNT-Sim domain (p.His143Ter), and two missense variants, p.Pro30Ala and p.Ser663Leu. Structural modeling suggested that the missense variants are likely to disrupt critical protein–protein interactions. The fifth variant was a synonymous change, c.1173G>A, p.(Ser391Ser), which was detected in five unrelated patients. Bioinformatic analysis predicted that this variant could alter splicing. Structural modeling suggested that the missense variants interfere with SIM1 function. This study expands the mutational spectrum of SIM1-linked monogenic obesity, reporting novel likely pathogenic frameshift variants, a missense variant, and a recurrent synonymous variant with a potential splice-site effect. The majority of the variants are predicted to affect the SIM1 protein. Our findings strengthen the critical role of the SIM1 gene in hypothalamic development and energy homeostasis. The results underscore the importance of including the SIM1 gene in genetic testing panels for children with severe obesity and hyperphagia, enabling precise diagnosis and potential future personalized management. Functional in vitro or in vivo validation of these variants is required to confirm their pathogenicity. Full article

This paper proposes JADEGBO, a hybrid gradient-based metaheuristic for solving complex single- and multi-constraint engineering design problems as well as cost-sensitive security optimisation tasks. The method combines Adaptive Differential Evolution with Optional External Archive (JADE), which provides self-adaptive exploration through p-best mutation, an external archive, and success-based parameter learning, with the Gradient-Based Optimiser (GBO), which contributes Newton-inspired gradient search rules and a local escaping operator. In the proposed scheme, JADE is first employed to discover promising regions of the search space, after which GBO performs an intensified local refinement of the best individuals inherited from JADE. The performance of JADEGBO is assessed on the CEC2017 single-objective benchmark suite and compared against a broad set of classical and recent metaheuristics. Statistical indicators, convergence curves, box plots, histograms, sensitivity analyses, and scatter plots show that the hybrid typically attains the best or near-best mean fitness, exhibits low run-to-run variance, and maintains a favourable balance between exploration and exploitation across rotated, shifted, and composite landscapes. To demonstrate practical relevance, JADEGBO is further applied to the following four well-known constrained engineering design problems: welded beam, pressure vessel, speed reducer, and three-bar truss design. The algorithm consistently produces feasible high-quality designs and closely matches or improves upon the best reported results while keeping computation time competitive. Full article

Group A rotaviruses (RVAs) remain the leading cause of acute gastroenteritis (AGE) in young children in low- and middle-income countries. In Brazil, the oral attenuated RVA vaccine (Rotarix^®), monovalent genotype G1P[8], is distributed by the national immunization program and has drastically reduced morbidity and mortality associated with RVA etiology. In this study, Rotarix^® G1P[8] was detected using specific qRT-PCR from the fecal shedding of children living in the Amazon region, and 18.3% (29/158) were positive and 75.8% (22/29) presented with AGE. The VP4 (VP8*) gene of these sheddings, submitted to Sanger nucleotide sequencing, showed an occurrence of mutations, including the silent mutation at 144C > G (one child) and the following missense mutations— 499T > C (F167L) (two children), 644G > C (C215S) (one child), and 787G > A (E263K) (one child). These mutations had no impact on the protein model structure in silico deduced from the VP4 (VP8*) mutants. The in silico protein model deduced from the VP4 (VP8*) nucleotide sequences, bound to type 1H sugar antigens (H1) and its precursor Lac-para-N-biose (LNB), had a stronger binding to the G1P[8] genotype, when compared to G3P[8]. Rotarix^® shedding was higher in HBGA secretors than in non-secretors (79.3%; 23/29). A total of 11.4% (18/158) of children with Rotarix^® G1P[8] shedding were unvaccinated, indicating the occurrence of indirect protection. Stability evidence of Rotarix^® VP4 (VP8*) spike protein from samples collected in vivo is presented. Full article

Background/Objectives: Immunotherapy has improved outcomes for selected patients with advanced non-small-cell lung cancer (NSCLC), yet the predictive value of individual biomarkers such as PD-L1 remains limited. Systemic inflammatory indices derived from routine blood tests may complement molecular and immunohistochemical features, offering a broader view of host–tumor immunobiology. Methods: We conducted a retrospective study of 298 patients with stage IIIB–IV NSCLC treated with immune checkpoint inhibitors (ICIs) at a tertiary oncology center between 2022 and 2024. Baseline neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune–inflammation index (SII) were collected alongside PD-L1 expression and molecular alterations (EGFR, KRAS, ALK, TP53). Patients were stratified into inflammatory–molecular clusters integrating these parameters. Associations with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated using Kaplan–Meier and multivariate Cox analyses. Results: Four distinct inflammatory–molecular clusters demonstrated significantly different outcomes (p < 0.001). Patients with low NLR and high PD-L1 expression (Cluster A) showed the highest ORR (41%), longest median PFS (13.0 months), and OS (22.5 months). The EGFR/ALK-driven, inflammation-dominant cluster (Cluster C) exhibited poor response (ORR 7%) and shortest survival (PFS 4.3 months). High NLR (HR 2.12), PD-L1 < 1% (HR 1.91), and EGFR mutation (HR 2.36) independently predicted shorter PFS. A combined model incorporating NLR, PD-L1, and molecular status outperformed individual biomarkers (AUC 0.82). Conclusions: Integrating systemic inflammatory indices with PD-L1 expression and molecular alterations identifies clinically meaningful NSCLC subgroups with distinct immunotherapy outcomes. This multidimensional approach improves prediction of ICI response and may enhance real-world patient stratification, particularly in settings with limited access to extended molecular profiling. Full article

Background: The KMT2A (MLL1) gene is altered in a variety of hematological malignancies and solid tumors. KMT2A-rearranged (KMT2Ar) AML represents a distinct subtype associated with poor outcomes and high relapse rate despite initial responsiveness to chemotherapy. Methods: A total of 3863 cases of AML peripheral blood samples were analyzed using the FoundationOne Heme combined comprehensive hybrid capture-based DNA and RNA sequencing assay. Results: Of the 3863 AML cases, 521 (13.4%) featured genomic alterations (GAs) in the KMT2A gene, 99.1% of which were large rearrangements (KMT2Ar). A total of 56.9% were males with a median age of 62 years. Of the KMT2Ar cases, there were 43.1% KMT2A duplications, 52.7% fusions, and 4.2% not otherwise specified rearrangements. A total of 0.9% of the KMT2A-altered AML cases were short variant mutations. There were no KMT2A (0%) amplifications or deletions. KMT2Ar cases were associated with increased GA frequencies in FLT3 (27.3% vs. 19.8%; p = 0.0002), KRAS (17.2% vs. 7.8%; p < 0.0001) (overall; 1.1% KRAS G12C), and IDH2 (16.0% vs. 10.4%; p < 0.0001), while KMT2A wild-type AML (KMT2Awt) had significantly increased GA frequencies in RUNX1 (20.7% vs. 15.8%; p = 0.0081), ASXL1 (16.6% vs. 10.5%; p = 0.0003), and TET2 (16.4% vs. 10.1%; p = 0.0002), NPM1 (17.5% vs. 0.2%; p < 0.0001), and TP53 (17.8% vs. 7.9%; p < 0.0001). Conclusions: KMT2A rearrangements are common in AML (13.4% of cases featured KMT2Ar). A total of 99.1% of alterations in KMT2A are large rearrangements, with fusions being the most commonly observed alteration (52.7% of total rearrangements). No amplifications or deletions were seen. This genomic landscape study highlights significant genomic differences between KMT2Ar and KMT2Awt AML patients, which may enrich our understanding of the molecular profile and clusters of mutations in AML. Full article

Targeted next-generation sequencing (tNGS) closes the gap between point-of-care rapid tests and phenotypic drug susceptibility testing (pDST) in drug-resistant tuberculosis (DR-TB). The 2025 World Health Organization (WHO) consolidated guidelines and the operational handbook place tNGS after initial automated nucleic acid amplification tests (aNAATs) for the delivery of catalogue-linked molecular drug susceptibility testing (DST) for a broad drug panel, reserving whole-genome sequencing (WGS) and/or pDST for discordance resolution, confirmation, and surveillance. This review summarizes (i) the core tNGS principles and panel design; (ii) platform-specific workflows for Illumina and Nanopore, including direct-from-sample implementations and typical turnaround times; (iii) catalogue-based interpretation against the 2023 WHO Mycobacterium tuberculosis mutation catalogue, with emphasis on bedaquiline/clofazimine (BDQ/CFZ) resistance and management of uncertain variants; (iv) pooled accuracy and sources of genotype–phenotype discordance; and (v) practical requirements for bioinformatics, quality assurance/external quality assessment (QA/EQA), and standardized reporting. We summarize operational and economic considerations (throughput, batching, and network design) to clarify where tNGS adds value compared with alternative strategies and to outline priority research needs, including (i) performance standards for culture-free tNGS, (ii) robust heteroresistance detection, (iii) standardized variant curation, and (iv) data-sharing frameworks to refine genotype–phenotype links. When embedded within validated QA/EQA frameworks and catalogue-linked reporting systems, tNGS can shorten the time to effective therapy by rapidly informing fluoroquinolone (FQ) susceptibility and providing early, tiered resistance signals for newer agents (e.g., BDQ), with indeterminate findings prompting reflex pDST/WGS. Full article

Early-onset colorectal cancer (EOCRC) continues to rise, with the steepest increases observed among Hispanic/Latino (H/L) populations, underscoring the urgency of identifying ancestry- and treatment-specific biomarkers. The JAK-STAT signaling axis plays a central role in colorectal tumor biology, yet its relevance under FOLFOX-based chemotherapy in EOCRC remains poorly defined. In this study, we evaluated 2515 colorectal cancer (CRC) cases (266 H/L; 2249 non-Hispanic White [NHW]), stratifying analyses by ancestry, age of onset, and FOLFOX exposure. Statistical comparisons were performed using Fisher’s exact and chi-square tests, and survival patterns were assessed via Kaplan–Meier analysis. To extend conventional analytics, we deployed AI-HOPE and AI-HOPE-JAK-STAT, conversational artificial intelligence platforms capable of harmonizing genomic, clinical, demographic, and treatment variables through natural language queries, to accelerate multi-parameter biomarker exploration. JAK-STAT pathway alterations showed marked variation by ancestry and treatment context. Among H/L EOCRC cases, alterations were significantly enriched in patients who did not receive FOLFOX compared with those who did (21.2% vs. 4.1%; p = 0.003). A similar pattern emerged in late-onset CRC (LOCRC) NHW patients, where alterations were more frequent without FOLFOX exposure (13.3% vs. 7.5%; p = 0.0002). Notably, JAK-STAT alterations were significantly more common in untreated H/L EOCRC compared with untreated NHW EOCRC (21.2% vs. 9.9%; p = 0.002). Survival analyses revealed that JAK-STAT pathway alterations conferred improved overall survival across several NHW strata, including EOCRC treated with FOLFOX (p = 0.0008), EOCRC not treated with FOLFOX (p = 0.07), and LOCRC not treated with FOLFOX (p = 0.01). These findings suggest that JAK-STAT alterations may function as ancestry- and treatment-dependent prognostic markers in EOCRC, particularly among disproportionately affected H/L patients. However, prognostic interpretation in H/L subgroups is limited by small mutation-positive sample sizes, reflecting historical underrepresentation and highlighting the need for larger ancestry-balanced studies. The integration of AI-enabled platforms streamlined analyses and reveals the potential of artificial intelligence to accelerate discovery and advance precision medicine for populations historically underrepresented in cancer genomics research. Full article