Pharmacogenomics and Personalized Medicine最新文献

{"title":"Association of the Reduced Function Met420del Polymorphism of SLC22A1 with Metformin-Induced Gastrointestinal Intolerance in Ethiopian Patients with Type 2 Diabetes Mellitus","authors":"Abraham Degaga, Sisay Sirgu, Hasniza Zaman Huri, Maw Shin Sim, Navin Kumar Loganadan, Tedla Kebede, Birhanemeskel Tegene, Ephrem Engidawork, Workineh Shibeshi","doi":"10.2147/pgpm.s457374","DOIUrl":"https://doi.org/10.2147/pgpm.s457374","url":null,"abstract":"<strong>Background:</strong> Despite its widespread use and favored profile, there are extensive variations in the treatment outcome of metformin therapy. Furthermore, studies reported that the inter-individual variability in the occurrence of metformin treatment associated side effects were related to the differences in individual genetic profiles. Thus, this study aimed to evaluate whether the reduced function methionine deletion at codon 420 (M<em>et420del</em>) variant of <em>SLC22A1</em> (rs72552763) is associated with metformin induced gastrointestinal intolerance in Ethiopian patients with type 2 diabetes mellitus (T2DM).<br/><strong>Patients and Methods:</strong> A retrospective observational study was conducted on 47 T2DM patients on metformin treatment for &lt; 3 years to assess the association of <em>SLC22A1</em> (rs72552763) polymorphism with metformin induced gastrointestinal intolerance. Accordingly, 24 metformin tolerant and 23 metformin intolerant individuals with T2DM were recruited. Genotyping of rs72552763 was performed using TaqMan^® Drug Metabolism Enzyme Genotyping Assay and its association to metformin induced gastrointestinal intolerance was assessed based on switching to a new class of glucose lowering agents or failure to up titrate dose due to metformin induced gastrointestinal intolerance. Chi-square, logistic regression and Mann–Whitney statistical tests were used as appropriate. Statistical significance was set at p &lt; 0.05.<br/><strong>Results:</strong> In our study, no significant association was observed between rs72552763 and metformin induced gastrointestinal intolerance. We found that the female gender and physical inactivity were risk factors for metformin gastrointestinal intolerance.<br/><strong>Conclusion:</strong> Our study found that the M<em>et420del</em> variant of <em>SLC22A1</em> (rs72552763) was not associated with metformin induced gastrointestinal intolerance in Ethiopian patients with T2DM. This is the study first to investigate the association of rs72552763 with metformin intolerance in the Ethiopian population with T2DM. However, the findings need to be cautiously interpreted given the relatively small sample size. In addition, a more complete investigation of <em>SLC22A1</em> variants would be required to fully assess the effect of the gene on metformin induced gastrointestinal intolerance as several variants with a more severe loss of function have been described.<br/><br/>","PeriodicalId":501056,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140834700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Three Liquid-Liquid Phase Separation-Related Genes Associated with Prognosis in Glioma","authors":"Ling Lv, Xin Zhang, Yajun Liu, Xutong Zhu, Ruihan Pan, Lifa Huang","doi":"10.2147/pgpm.s442000","DOIUrl":"https://doi.org/10.2147/pgpm.s442000","url":null,"abstract":"<strong>Purpose:</strong> Dysregulated liquid-liquid phase separation (LLPS) instigates tumorigenesis through biomolecular condensate dysfunction. However, the association between LLPS-associated genes and glioma remains underexplored.<br/><strong>Patients and Methods:</strong> Differentially expressed genes (DEGs) of glioma were obtained from the GSE50161 dataset, including 34 glioma and 13 normal samples. We analyzed differentially expressed LLPS-related genes in glioma from public databases. These genes informed refined molecular subtyping on the TCGA-glioma dataset. CIBERSORT assessed immune cell infiltration across three subclusters. A prognostic model was devised using univariate and lasso Cox regressions on intersecting genes. Prognostic gene expression was validated in glioma cells via RT-qPCR.<br/><strong>Results:</strong> A total of 673 differentially expressed LLPS-associated genes were identified in glioma. Three distinct molecular subtypes (C1, C2, and C3) of glioma were obtained with a marked variance in the expression of immune checkpoint genes PD1 and PDL1. Differences in immune cell infiltration were observed across subtypes. In addition, a tri-gene prognostic signature (<em>TAGLN2, NTNG2</em>, and <em>IGF2BP2</em>) was derived with significant survival differences between high and low-risk groups. The prognostic model displayed impressive AUC values for 1, 3, and 5-year survival in both training and validation sets. Further analysis highlighted a notable correlation between the three prognostic genes and immune cells in glioma samples. Furthermore, we found the upregulation of TAGLN2 and IGF2BP2 and the downregulation of NTNG2 in glioma tumors and cells.<br/><strong>Conclusion:</strong> This study innovatively uncovers the significant role of LLPS-related genes in glioma tumor grading and prognosis. The constructed tri-gene prognostic model holds promise for enhancing personalized prognosis assessments and optimizing immunotherapy strategies for glioma patients.<br/><br/><strong>Keywords:</strong> liquid-liquid phase separation, glioma, prognostic model, molecular subtype, immune cell infiltration<br/>","PeriodicalId":501056,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":"87 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140634859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ACE Gene Mutations (rs577350502) in Early-Onset and Recurrent Myocardial Infarction: A Case Report and Review","authors":"Xiaoxi Deng, Xiaofei Guo, Xiaojie Chen, Xinyu Zeng, Jiamin Guo, Xin Bai, Ping Zhang, Yuan Wang","doi":"10.2147/pgpm.s455740","DOIUrl":"https://doi.org/10.2147/pgpm.s455740","url":null,"abstract":"<strong>Background:</strong> Acute myocardial infarction (AMI) is a severe acute coronary syndrome, demonstrating a trend toward affecting younger individuals in recent years. The association between early-onset myocardial infarction and single nucleotide polymorphism necessitates further exploration and evaluation.<br/><strong>Case description:</strong> We present a case of a patient experiencing early-onset and recurrent myocardial infarction. The patient underwent stent implantation for myocardial infarction at the age of 53 and subsequently encountered two more myocardial infarctions within a span of 16 years. Following interventional therapy, genetic testing was conducted to assess the efficacy of subsequent anti-heart failure medications, with the aim to preemptively address heart failure risks. Genetic testing revealed a mutation in the angiotensin-converting enzyme (ACE) gene (rs577350502, g.63488533C&gt;A), characterized by an intron-deletion single nucleotide variant.<br/><strong>Conclusion:</strong> While this variant has not been previously reported to be associated with any specific disease, we hypothesize that it may contribute to the susceptibility and risk of myocardial infarction and coronary heart disease in the patient under consideration. This observation underscores the significance of investigating the insertion/deletion polymorphisms of the ACE gene in the context of AMI and emphasizes the necessity for further validation of this variant and other genetic markers associated with AMI in related diseases.<br/><br/>","PeriodicalId":501056,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":"62 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140630664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of a Novel Mitochondrial tRNA Mutation in Chinese Family with Type 2 Diabetes Mellitus","authors":"Xing Li, Jinyao Shang, Shuang Li, Yue Wang","doi":"10.2147/pgpm.s438978","DOIUrl":"https://doi.org/10.2147/pgpm.s438978","url":null,"abstract":"<strong>Background:</strong> Mutations in mitochondrial tRNA (mt-tRNA) could be the origin of some type 2 diabetes mellitus (T2DM) cases, but the mechanism remained largely unknown.<br/><strong>Aim:</strong> The aim of this study was to assess the impact of a novel mitochondrial tRNA^Cys/tRNA^Tyr A5826G mutation on the development and progression of T2DM.<br/><strong>Methods:</strong> A four-generation Han Chinese family with maternally inherited diabetes underwent clinical, genetic and biochemical analyses. The mitochondrial DNA (mtDNA) mutations of three matrilineal relatives were screened by PCR-Sanger sequencing. Furthermore, to see whether m.A5826G mutations affected mitochondrial functions, the cybrid cell lines were derived from three subjects with m.A5826G mutation and three controls without this mutation. ATP was evaluated by luminescent cell viability assay, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) were determined by flow cytometry. The student’s two-tailed, unpaired <em>t</em>-test was used to assess the statistical significance between the control and mutant results.<br/><strong>Results:</strong> The age at onset of diabetes in this pedigree varied from 40 to 63 years, with an average of 54 years. Mutational analysis of mitochondrial genomes revealed the presence of a novel m.A5826G mutation. Interestingly, the m.A5826G mutation occurred at the conjunction between tRNA^Cys and tRNA^Tyr, a very conserved position that was critical for tRNAs processing and functions. Using trans-mitochondrial cybrid cells, we found that mutant cells carrying the m.A5826G showed approximately 36.5% and 22.4% reductions in ATP and MMP, respectively. By contrast, mitochondrial ROS levels increased approximately 33.3%, as compared with the wild type cells.<br/><strong>Conclusion:</strong> A novel m.A5826G mutation was identified in a pedigree with T2DM, and this mutation would lead to mitochondrial dysfunction. Thus, the genetic spectrum of mitochondrial diabetes was expanded by including m.A5826G mutation in tRNA^Cys/tRNA^Tyr, our study provided novel insight into the molecular pathogenesis, early diagnosis, prevention and clinical treatment for mitochondrial diabetes.<br/><br/>","PeriodicalId":501056,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":"458 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140608967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Severe Vincristine-Induced Peripheral Neuropathic Weakness in Both Lower Limbs in an Asian Adolescent with CYP3A4 rs2740574 TT Genotype","authors":"Dongdong Zhang, Jie Bai","doi":"10.2147/pgpm.s460878","DOIUrl":"https://doi.org/10.2147/pgpm.s460878","url":null,"abstract":"<strong>Background:</strong> Vincristine (VCR)-induced peripheral neuropathy (VIPN) is a common adverse reaction during cancer treatment, typically characterized by numbness and paresthesias. This study aimed to report a rare case of VIPN with an atypical genotype, manifesting as grade 3 weakness of the lower limbs.<br/><strong>Case Presentation:</strong> A 19-year-old man, diagnosed with alveolar rhabdomyosarcoma for 8 months, was transferred to our hospital for further treatment after the failure of first-line treatment. He developed severe long-standing weakness in both lower limbs and could not walk after four sessions of second-line chemotherapy. The diagnosis of VIPN was confirmed based on the patient’s physical examination, imaging studies, electromyogram results, and treatment history. Furthermore, the pharmacogenetic analysis indicated that the patient harbored <em>CYP3A4</em> rs2740574 TT genotypes.<br/><strong>Conclusion:</strong> We have reported for the first time a VIPN patient whose main clinical manifestation is severe weakness in both lower limbs, accompanied by the <em>CYP3A4</em> rs2740574 TT phenotype. This case may provide new information on the phenotypic features of VIPN, and may help to better understand the disease pathogenesis and contributing factors.<br/><br/>","PeriodicalId":501056,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140569923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Downregulation of NAT1 Expression is Associated with Poor Prognosis and Immune Infiltration in COAD","authors":"Houxi Xu, Hongqun Zhang, Songxian Sun, Jingyuan Zhang, Jiege Huo, Chunxiang Zhou","doi":"10.2147/pgpm.s455490","DOIUrl":"https://doi.org/10.2147/pgpm.s455490","url":null,"abstract":"<strong>Background:</strong> An increasing corpus of evidence has identified the involvement of N-acetyltransferase 1 (NAT1), a member of the NAT family, in the progression of various cancers. However, the specific function of NAT1 in colon cancer (COAD) remains elusive. This study aims to decip her the role of NAT1 in COAD and its associated mechanisms.<br/><strong>Methods:</strong> The Tumor Immunity Evaluation Resource (TIMER), The Cancer Genome Atlas (TCGA), and the Gene Expression Omnibus (GEO) databases were employed to assess the NAT1 expression level in COAD. The differential expression between COAD and normal colon tissue was further validated using quantitative real-time reverse-transcription PCR (RT-qPCR) and Western blot (WB) analyses. Additionally, survival analysis of NAT1 in COAD was carried out using the PrognoScan database and TCGA dataset. The functions of NAT1 were explored through gene set enrichment analysis (GSEA) and immuno-infiltration analysis.<br/><strong>Results:</strong> There was a significant reduction in NAT1 expression in COAD samples compared to normal tissue. Notably, low NAT1 expression in COAD correlated significantly with various clinical parameters such as tumor stage (T stage, N stage, M stage, pathologic stage), primary therapy outcome, carcinoembryonic antigen (CEA) level, and lymphatic invasion. The downregulation of NAT1 was also strongly linked with poor outcomes in overall survival (OS), progression-free interval (PFI), and disease-specific survival (DSS). Cox regression analysis highlighted NAT1 as an independent prognostic indicator for overall survival in COAD patients. GSEA results revealed NAT1’s involvement in multiple pathways, including the neuroactive ligand-receptor interaction, olfactory transduction, olfactory signaling, extracellular matrix receptor interaction, calcium signaling, and focal adhesion pathways. Furthermore, NAT1 expression was found to significantly correlate with infiltration levels of various immune cells.<br/><strong>Conclusion:</strong> The findings reveal NAT1’s potential as a valuable prognostic biomarker for COAD. Moreover, its associated mechanisms offer insights that might pave the way for therapeutic interventions for COAD patients.<br/><br/>","PeriodicalId":501056,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":"81 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140569683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Lower Grade Glioma Antigens Based on Ferroptosis Status for mRNA Vaccine Development","authors":"Zhenxiang Zhao, Na Xing, Hao Guo, Jianfeng Li, Guozhu Sun","doi":"10.2147/pgpm.s449230","DOIUrl":"https://doi.org/10.2147/pgpm.s449230","url":null,"abstract":"<strong>Purpose:</strong> mRNA vaccines represent a promising and innovative strategy within the realm of cancer immunotherapy. However, their efficacy in treating lower-grade glioma (LGG) requires evaluation. Ferroptosis exhibits close associations with the initiation, evolution, and suppression of cancer. In this study, we explored the landscape of the ferroptosis-associated tumor microenvironment to facilitate the development of mRNA vaccines for LGG patients.<br/><strong>Patients and Methods:</strong> Genomic and clinical data of the LGG patients was obtained from the Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. Ferroptosis-related tumor antigens were identified based on differential expression, mutation status, correlation with antigen-presenting cells, and prognosis, relevance to immunogenic cell death (ICD). Antigen expression levels in LGG specimens and cell lines were validated using real time-polymerase chain reaction (RT-PCR). Consensus clustering was employed for patient classification. The immune landscapes of ferroptosis subtypes were further characterized, including immune responses, prognostic ability, tumor microenvironment, and tumor-related signatures.<br/><strong>Results:</strong> Five tumor antigens, namely, HOTAIR, IDO1, KIF20A, NR5A2, and RRM2 were identified in LGG. RT-PCR demonstrated higher expression of these genes in LGG compared to the control. Twelve gene modules and four ferroptosis subtypes (FS1-FS4) of LGG were defined. FS2 and FS4, characterized as “cold” tumors due to their decreased tumor mutation burden (TMB) and immune checkpoint proteins (ICPs), were deemed appropriate candidates for the mRNA vaccine.<br/><strong>Conclusion:</strong> HOTAIR, IDO1, KIF20A, NR5A2, and RRM2 were identified as promising candidate antigens for the development of an LGG mRNA vaccine, particularly offering potential benefits to FS2 and FS4 patients.<br/><br/><strong>Keywords:</strong> ferroptosis, lower grade glioma, mRNA vaccine, immunotherapy<br/>","PeriodicalId":501056,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140569902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploration of the Correlation Between GRHL1 Expression and Tumor Microenvironment in Endometrial Cancer and Immunotherapy","authors":"Suyang Guo, Wenqi Bai, Fengjie Cui, Xin Chen, Xiaojing Fang, Honghong Shen, Xianhua Gu","doi":"10.2147/pgpm.s453061","DOIUrl":"https://doi.org/10.2147/pgpm.s453061","url":null,"abstract":"<strong>Introduction:</strong> <em>GRHL1</em> belongs to the family of Grainyhead-like (GRHL). Previous studies have shown that dysregulation of growth and survival pathways is associated with the GRHL family of gene cancers. Immunotherapy with checkpoint inhibitors has changed the treatment paradigm for many tumors, including endometrial cancer (EC). However, the effect of <em>GRHL1</em> on immunotherapy in EC and its relationship with immune cell infiltration are poorly understood.<br/><strong>Methods:</strong> Differential expression of <em>GRHL1</em> between EC and normal EC tissues was analyzed by searching the TCGA database, and the results were verified utilizing immunohistochemistry analyses. Next, the relationship between <em>GRHL1</em>, CD8+ T cells and tumor microenvironment (TME) was also investigated, and the effect of <em>GRHL1</em> expression on immunotherapy in EC was evaluated.<br/><strong>Results:</strong> According to the findings, EC tissues had elevated expression levels of <em>GRHL1</em> relative to normal tissues. Patients with EC who expressed <em>GRHL1</em> at high levels experienced worse overall survival (OS) and Progression-free survival (PFS) than those whose expression was lower. In addition, <em>GRHL1</em> expression was negatively correlated with CD8+ T cells, and patients with high <em>GRHL1</em> expression were less effective in receiving immunotherapy.<br/><strong>Conclusion:</strong> The expression of <em>GRHL1</em> was high in EC patients, and high expression of <em>GRHL1</em> inhibits the proliferation of CD8+ T cells in the tumor microenvironment of EC and affect the efficacy of immunotherapy.<br/><br/><strong>Keywords:</strong> <em>GRHL1</em>, endometrial cancer, tumor microenvironment, CD8+ T cells, immunotherapy<br/>","PeriodicalId":501056,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140569903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Association Between Mitochondrial tRNAGlu Variants and Hearing Loss: A Case-Control Study","authors":"Xuejiao Yu, Sheng Li, Qinxian Guo, Jianhang Leng, Yu Ding","doi":"10.2147/pgpm.s441281","DOIUrl":"https://doi.org/10.2147/pgpm.s441281","url":null,"abstract":"<strong>Purpose:</strong> This study aimed to examine the frequencies of mt-tRNA^Glu variants in 180 pediatric patients with non-syndromic hearing loss (NSHL) and 100 controls.<br/><strong>Methods:</strong> Sanger sequencing was performed to screen for mt-tRNA^Glu variants. These mitochondrial DNA (mtDNA) pathogenic mutations were further assessed using phylogenetic conservation and haplogroup analyses. We also traced the origins of the family history of probands carrying potential pathogenic mtDNA mutations. Mitochondrial functions including mtDNA content, ATP and reactive oxygen species (ROS) were examined in cells derived from patients carrying the mt-tRNA^Glu A14692G and CO1/tRNA^Ser(UCN) G7444A variants and controls.<br/><strong>Results:</strong> We identified four possible pathogenic variants: m.T14709C, m.A14683G, m.A14692G and m.A14693G, which were found in NSHL patients but not in controls. Genetic counseling suggested that one child with the m.A14692G variant had a family history of NSHL. Sequence analysis of mtDNA suggested the presence of the CO1/tRNA^Ser(UCN) G7444A and mt-tRNA^Glu A14692G variants. Molecular analysis suggested that, compared with the controls, patients with these variants exhibited much lower mtDNA copy numbers, ATP production, whereas ROS levels increased (<em>p</em>&lt; 0.05 for all), suggesting that the m.A14692G and m.G7444A variants led to mitochondrial dysfunction.<br/><strong>Conclusion:</strong> mt-tRNA^Glu variants are important risk factors for NSHL.<br/><br/><strong>Plain Language Summary:</strong> The main aim of our study was to explore the association between the mt-tRNA^Glu variants and hearing loss. We found that m.T14709C, m.A14683G, m.A14692G and m.A14693G variants were associated with hearing impairments, these variants localized at extremely conserved nucleotides of mt-tRNA^Glu and may result a failure in tRNA metabolism, furthermore, patients with mt-tRNA^Glu variants exhibited much lower levels of mtDNA copy number, ATP as compared with controls, whereas ROS increased. As a result, mt-tRNA^Glu variants may serve as biomarkers for mitochondrial deafness, and screening for tRNA^Glu variants is recommended for early detection and diagnosis of mitochondrial deafness.<br/><br/><strong>Keywords:</strong> deafness, mitochondrial tRNA^Glu variants, pediatrics, tRNA metabolism<br/>","PeriodicalId":501056,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140316101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural Language Processing for Radiation Oncology: Personalizing Treatment Pathways","authors":"Hui Lin, Lisa Ni, Christina Phuong, Julian C Hong","doi":"10.2147/pgpm.s396971","DOIUrl":"https://doi.org/10.2147/pgpm.s396971","url":null,"abstract":"<strong>Abstract:</strong> Natural language processing (NLP), a technology that translates human language into machine-readable data, is revolutionizing numerous sectors, including cancer care. This review outlines the evolution of NLP and its potential for crafting personalized treatment pathways for cancer patients. Leveraging NLP’s ability to transform unstructured medical data into structured learnable formats, researchers can tap into the potential of big data for clinical and research applications. Significant advancements in NLP have spurred interest in developing tools that automate information extraction from clinical text, potentially transforming medical research and clinical practices in radiation oncology. Applications discussed include symptom and toxicity monitoring, identification of social determinants of health, improving patient-physician communication, patient education, and predictive modeling. However, several challenges impede the full realization of NLP’s benefits, such as privacy and security concerns, biases in NLP models, and the interpretability and generalizability of these models. Overcoming these challenges necessitates a collaborative effort between computer scientists and the radiation oncology community. This paper serves as a comprehensive guide to understanding the intricacies of NLP algorithms, their performance assessment, past research contributions, and the future of NLP in radiation oncology research and clinics.<br/><br/><strong>Keywords:</strong> artificial intelligence, personalized medicine, radiation therapy, natural language processing<br/>","PeriodicalId":501056,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139770477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}