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PURPOSE: A critical task in oncology is extracting information related to cancer metastasis from electronic health records. Metastasis-related information is crucial for planning treatment, evaluating patient prognoses, and cancer research. However, the unstructured way in which findings of distant metastasis are often written in radiology reports makes it difficult to extract information automatically. The main aim of this study was to extract distant metastasis findings from free-text imaging and nuclear medicine reports to classify the patient status according to the presence or absence of distant metastasis. MATERIALS AND METHODS: We created a distant metastasis annotated corpus using positron emission tomography-computed tomography and computed tomography reports of patients with prostate, colorectal, and breast cancers. Entities were labeled M1 or M0 according to affirmative or negative metastasis descriptions. We used a named entity recognition model on the basis of a bidirectional long short-term memory model and conditional random fields to identify entities. Mentions were subsequently used to classify whole reports into M1 or M0. RESULTS: The model detected distant metastasis mentions with a weighted average F1 score performance of 0.84. Whole reports were classified with an F1 score of 0.92 for M0 documents and 0.90 for M1 documents. CONCLUSION: These results show the usefulness of the model in detecting distant metastasis findings in three different types of cancer and the consequent classification of reports. The relevance of this study is to generate structured distant metastasis information from free-text imaging reports in Spanish. In addition, the manually annotated corpus, annotation guidelines, and code are freely released to the research community.

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Background and aims: Latin American populations remain underrepresented in genetic studies of inflammatory bowel diseases (IBDs). Most genetic association studies of IBD rely on Caucasian, African, and Asian individuals. These associations have yet to be evaluated in detail in the Andean region of South America. We explored the contribution of IBD-reported genetic risk variants to a Chilean cohort and the ancestry contribution to IBD in this cohort. Methods: A total of 192 Chilean IBD patients were genotyped using Illumina's Global Screening Array. Genotype data were combined with similar information from 3,147 Chilean controls. The proportions of Aymara, African, European, and Mapuche ancestries were estimated using the software ADMIXTURE. We calculated the odds ratios (ORs) and 95% confidence intervals (CIs) for gender, age, and ancestry proportions. We also explored associations with previously reported IBD-risk variants independently and in conjunction with genetic ancestry. Results: The first and third quartiles of the proportion of Mapuche ancestry in IBD patients were 24.7 and 34.2%, respectively, and the corresponding OR was 2.30 (95%CI 1.52-3.48) for the lowest vs. the highest group. Only one variant (rs7210086) of the 180 reported IBD-risk SNPs was associated with IBD risk in the Chilean cohort (adjusted P = 0.01). This variant is related to myeloid cells. Conclusion: The type and proportion of Native American ancestry in Chileans seem to be associated with IBD risk. Variants associated with IBD risk in this Andean region were related to myeloid cells and the innate immune response.

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Lactose intolerance (LI) and vitamin D deficiency (VDD) have been linked to inflammatory bowel disease (IBD). We conducted an observational study in 192 Chilean IBD patients to investigate the prevalence of a specific gene variant (LCT-13910 CC genotype) associated with LI and the prevalence of VDD/Vitamin D Receptor (VDR) gene variants. Blood samples were analyzed using Illumina's Infinium Global Screening Array. The LCT-13910 CC genotype was found in 61% of IBD patients, similar to Chilean Hispanic controls and lower than Chilean Amerindian controls. The frequency of the LCT-13910-C allele in Chilean IBD patients (0.79) was comparable to the general population and higher than Europeans (0.49). Regarding VDR and VDD variants, in our study, the rs12785878-GG variant was associated with an increased risk of IBD (OR = 2.64, CI = 1.61-4.32; p-value = 0.001). Sixty-one percent of the Chilean IBD cohort have a genetic predisposition to lactose malabsorption, and a significant proportion exhibit genetic variants associated with VDD/VDR. Screening for LI and VDD is crucial in this Latin American IBD population.

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This paper aims to review, systematically synthesize, and analyze fragmented information about the importance of coat color in local goats and its relationship with productivity and other important traits. Topics on current research on color expression are addressed, the relationship that has as a mechanism of environmental adaptation, its relationship with the production of meat, milk, and derivates, and the economic value of this characteristic. The use of this attribute as a tool to establish selection criteria in breeding programs based on results reported in the scientific literature is significant, particularly for low-income production systems, where the implementation of classic genetic improvement schemes is limited due to the lack of productive information, which is distinctive of extensive marginal or low scaled production systems around the world.

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This study aimed to analyze the molecular characteristics of oral epithelial dysplasia (OED), highlighting the pathways and variants of genes that are frequently mutated in oral squamous cell carcinoma (OSCC) and other cancers. Ten archival OED cases were retrieved for retrospective clinicopathological analysis and exome sequencing. Comparative genomic analysis was performed between high-grade dysplasia (HGD) and low-grade dysplasia (LGD), focusing on 57 well-known cancer genes, of which 10 were previously described as the most mutated in OSCC. HGD cases had significantly more variants; however, a similar mutational landscape to OSCC was observed in both groups. CASP8+FAT1/HRAS, TP53, and miscellaneous molecular signatures were also present. FAT1 is the gene that is most affected by pathogenic variants. Hierarchical divisive clustering showed division between the two groups: "HGD-like cluster" with 4HGD and 2LGD and "LGD-like cluster" with 4 LGD. MLL4 pathogenic variants were exclusively in the "LGD-like cluster". TP53 was affected in one case of HGD; however, its pathway was usually altered. We describe new insights into the genetic basis of epithelial malignant transformation by genomic analysis, highlighting those associated with FAT1 and TP53. Some LGDs presented a similar mutational landscape to HGD after cluster analysis. Perhaps molecular alterations have not yet been reflected in histomorphology. The relative risk of malignant transformation in this molecular subgroup should be addressed in future studies.

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Abstract This study aimed to analyze the molecular characteristics of oral epithelial dysplasia (OED), highlighting the pathways and variants of genes that are frequently mutated in oral squamous cell carcinoma (OSCC) and other cancers. Ten archival OED cases were retrieved for retrospective clinicopathological analysis and exome sequencing. Comparative genomic analysis was performed between high-grade dysplasia (HGD) and low-grade dysplasia (LGD), focusing on 57 well-known cancer genes, of which 10 were previously described as the most mutated in OSCC. HGD cases had significantly more variants; however, a similar mutational landscape to OSCC was observed in both groups. CASP8+FAT1/HRAS, TP53, and miscellaneous molecular signatures were also present. FAT1 is the gene that is most affected by pathogenic variants. Hierarchical divisive clustering showed division between the two groups: "HGD-like cluster" with 4HGD and 2LGD and "LGD-like cluster" with 4 LGD. MLL4 pathogenic variants were exclusively in the "LGD-like cluster". TP53 was affected in one case of HGD; however, its pathway was usually altered. We describe new insights into the genetic basis of epithelial malignant transformation by genomic analysis, highlighting those associated with FAT1 and TP53. Some LGDs presented a similar mutational landscape to HGD after cluster analysis. Perhaps molecular alterations have not yet been reflected in histomorphology. The relative risk of malignant transformation in this molecular subgroup should be addressed in future studies.

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Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn disease (CD), has emerged as a global disease with an increasing incidence in developing and newly industrialized regions such as South America. This global rise offers the opportunity to explore the differences and similarities in disease presentation and outcomes across different genetic backgrounds and geographic locations. Our study includes 265 IBD patients. We performed an exploratory analysis of the databases of Chilean and North American IBD patients to compare the clinical phenotypes between the cohorts. We employed an unsupervised machine-learning approach using principal component analysis, uniform manifold approximation, and projection, among others, for each disease. Finally, we predicted the cohort (North American vs Chilean) using a random forest. Several unsupervised machine learning methods have separated the 2 main groups, supporting the differences between North American and Chilean patients with each disease. The variables that explained the loadings of the clinical metadata on the principal components were related to the therapies and disease extension/location at diagnosis. Our random forest models were trained for cohort classification based on clinical characteristics, obtaining high accuracy (0.86 = UC; 0.79 = CD). Similarly, variables related to therapy and disease extension/location had a high Gini index. Similarly, univariate analysis showed a later CD age at diagnosis in Chilean IBD patients (37 vs 24; P = .005). Our study suggests a clinical difference between North American and Chilean IBD patients: later CD age at diagnosis with a predominantly less aggressive phenotype (39% vs 54% B1) and more limited disease, despite fewer biological therapies being used in Chile for both diseases.

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BACKGROUND: A significant proportion of the clinical record is in free text format, making it difficult to extract key information and make secondary use of patient data. Automatic detection of information within narratives initially requires humans, following specific protocols and rules, to identify medical entities of interest. AIM: To build a linguistic resource of annotated medical entities on texts produced in Chilean hospitals. MATERIAL AND METHODS: A clinical corpus was constructed using 150 referrals in public hospitals. Three annotators identified six medical entities: clinical findings, diagnoses, body parts, medications, abbreviations, and family members. An annotation scheme was designed, and an iterative approach to train the annotators was applied. The F1-Score metric was used to assess the progress of the annotator's agreement during their training. RESULTS: An average F1-Score of 0.73 was observed at the beginning of the project. After the training period, it increased to 0.87. Annotation of clinical findings and body parts showed significant discrepancy, while abbreviations, medications, and family members showed high agreement. CONCLUSIONS: A linguistic resource with annotated medical entities on texts produced in Chilean hospitals was built and made available, working with annotators related to medicine. The iterative annotation approach allowed us to improve performance metrics. The corpus and annotation protocols will be released to the research community.

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Background: A significant proportion of the clinical record is in free text format, making it difficult to extract key information and make secondary use of patient data. Automatic detection of information within narratives initially requires humans, following specific protocols and rules, to identify medical entities of interest. Aim: To build a linguistic resource of annotated medical entities on texts produced in Chilean hospitals. Material and Methods: A clinical corpus was constructed using 150 referrals in public hospitals. Three annotators identified six medical entities: clinical findings, diagnoses, body parts, medications, abbreviations, and family members. An annotation scheme was designed, and an iterative approach to train the annotators was applied. The F1-Score metric was used to assess the progress of the annotator's agreement during their training. Results: An average F1-Score of 0.73 was observed at the beginning of the project. After the training period, it increased to 0.87. Annotation of clinical findings and body parts showed significant discrepancy, while abbreviations, medications, and family members showed high agreement. Conclusions: A linguistic resource with annotated medical entities on texts produced in Chilean hospitals was built and made available, working with annotators related to medicine. The iterative annotation approach allowed us to improve performance metrics. The corpus and annotation protocols will be released to the research community.

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Increased expression of the TRPM4 channel has been reported to be associated with the progression of prostate cancer. However, the molecular mechanism underlying its effect remains unknown. This work found that decreasing TRPM4 levels leads to the reduced proliferation of PC3 cells. This effect was associated with a decrease in total ß-catenin protein levels and its nuclear localization, and a significant reduction in Tcf/Lef transcriptional activity. Moreover, TRPM4 silencing increases the Ser33/Ser37/Thr41 ß-catenin phosphorylated population and reduces the phosphorylation of GSK-3ß at Ser9, suggesting an increase in ß-catenin degradation as the underlying mechanism. Conversely, TRPM4 overexpression in LNCaP cells increases the Ser9 inhibitory phosphorylation of GSK-3ß and the total levels of ß-catenin and its nonphosphorylated form. Finally, PC3 cells with reduced levels of TRPM4 showed a decrease in basal and stimulated phosphoactivation of Akt1, which is likely responsible for the decrease in GSK-3ß activity in these cells. Our results also suggest that the effect of TRPM4 on Akt1 is probably mediated by an alteration in the calcium/calmodulin-EGFR axis, linking TRPM4 activity with the observed effects in ß-catenin-related signaling pathways. These results suggest a role for TRPM4 channels in ß-catenin oncogene signaling and underlying mechanisms, highlighting this ion channel as a new potential target for future therapies in prostate cancer.

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