Genomic tools for early selection among Thoroughbreds and Polo Argentino horses for practicing polo.

The Polo Argentino (PA) horse is a recognized breed, developed originally by mixing crossbred and Thoroughbred (TB) horses to play polo. Early PA selection is difficult due to unreliable performance estimations. This study investigated the usefulness of genomic markers previously linked to morphological and functional traits as a tool for the early selection of PA. To this, we genotyped 520 PA and 30 TB horses using the Equine GGPArray (Illumina, n = 71,778 SNPs). Analyses included a genetic characterization of six genetic markers associated with behavioral (DRD4), muscular development (MSTN), and body size (LCORL, HMGA6, ZFAT, and LASP1) genes. Genetic differences in the DRD4, MSTN, and LCORL SNP were found between the two breeds, in the last two FST index between breeds was 0.13 and 0.6, respectively (p < 0.01). In DRD4, G allele was the more prevalent in PA (0.56 vs 0.45 in TB, p < 0.05), but no differences were observed between the genotypes associated with phenotypes. In MSTN, heterozygous genotypes were the most common in PA (48 %), with a significant decrease in AA (Hardy-Weinberg p < 0.05), suggesting a negative selection against it in polo horses. In body size, HMGA2 was monomorphic in all horses, while ZFAT and LASP1 SNP showed higher variability. Interestingly, 99 % of PA showed a TT genotype in LCORL (only 66 % in TB), demonstrating selection for smaller horses. Our results suggest that empirical selection in PA has generated an incipient genomic differentiation in discrete traits which could be used as a marker-assisted selection tool for early selection of polo horses.

Genetic analysis of cervical cancer with lymph node metastasis.

OBJECTIVE: To find out the differences in gene characteristics between cervical cancer patients with and without lymph node metastasis, and to provide reference for therapy. METHODS: From January 2018 to June 2022, recurrent cervical cancer patients 39 cases with lymph node metastasis and 73 cases without lymph node metastasis underwent testing of 1,021 cancer-related genes by next-generation sequencing. Maftools software was used to analyze somatic single nucleotide/insertion-deletion variation mutation, co-occurring mutation, cosmic mutation characteristics, oncogenic signaling pathways. RESULTS: EP300 and FBXW7 were significantly enriched in lymph node-positive patients. Lymph node-positive patients with EP300 or FBXW7 mutations had lower overall survival (OS) after recurrence. Both lymph node-positive and -negative patients had plenty of co-occurring mutations but few mutually exclusive mutations. Lymph node-positive co-occurring mutation number ≥6 had lower OS, while lymph node-negative co-occurring mutation number ≥3 had lower OS after recurrence. The etiology of SBS3 was defects in DNA double strand break repair by homologous recombination, which exclusively exist in lymph node-positive patients. There was no difference in median tumor mutation burden (TMB) between positive and negative lymph nodes, but TMB was significantly associated with PIK3CA mutation. CONCLUSION: The somatic SNV/Indels of EP300 and FBXW7, SBS3 homologous recombination-mediated DNA repair defect were enriched in lymph node-positive patients. For lymph node-positive patients, EP300 or FBXW7 mutations predicted poor prognosis. No matter lymph node-positive or negative, more co-occurring mutation number predicted poor prognosis. PIK3CA mutation may account for the higher TMB and help identify patients who benefit from immunotherapy.

Tracing the fine-scale demographic history and recent admixture in Hmong-Mien speakers.

The linguistic, historical, and subsistent uniqueness of Hmong-Mien (HM) speakers offers a wonderful opportunity to investigate how these factors impact the genetic structure. The genetic differentiation among HM speakers and their population history are not well characterized. Here, we generate genome-wide data from 65 Yao ethnicity samples and analyze them with published data, particularly by leveraging haplotype-based methods. We determined that the fine-scale genetic substructure of HM speakers corresponds better with linguistic classification than with geography. Particularly, parallels between serial founder events and language differentiations can be observed in West Hmongic speakers. Multiple lines of evidence indicate that ~500-year-old GaoHuaHua individuals are most closely related to West Hmongic-speaking Bunu. The strong genetic bottleneck of some HM-speaking groups, especially Bunu, could potentially be associated with their long-term practice of swidden agriculture to some degree. The inferred admixture dates for most of the HM speakers overlap with the reign of the Ming dynasty (1368-1644 CE). Besides a common genetic origin for HM speakers, their genetic ancestry is shared primarily with neighboring Han Chinese and Tai-Kadai speakers in south China. In conclusion, our analyses reveal that recent isolation and admixture events have contributed to the genetic population history of present-day HM speakers.

A Systematic Review of Epigenetics of Endometriosis.

Objective: To assess the current literature evaluating the epigenetics of endometriosis in humans. Evidence Review: A systematic review was conducted in accordance with the PRISMA guidelines within PubMed, EBSCOhost, Cochrane Library, Embase, Scopus, and Web of Science Core Collection. A comprehensive search strategy was developed by a data informationist. Observational and interventional studies assessing epigenetics in humans published in English up to January 15th, 2023, were included. Two reviewers independently screened studies evaluating the role of epigenetics in endometriosis. The risk of bias was assessed using Cochrane RoB 2.0 tool and the Newcastle-Ottawa scale. Extracted data were analyzed descriptively. Results: We identified 18.639 studies, of which 57 were included, comprising 1.623 patients with endometriosis and 1.243 controls. Among the 57 studies included, 50 (88%) were case-control studies, and 7 (12%) were cross-sectional. Fifty-nine percent of the studies were Asian, 25% were from America, 14% were European, and 2% were from Africa. Acetylation and methylation were the two main key histone modifications that were centered in this review. Accordingly, we classified the studies as those focusing on genome-wide methylation and those on histone acetylation. Several studies identified an association between endometriosis and hypermethylated genes, including the PGR-B, SF-1, and RASSF1A. The genes HOXA10, COX-2, IL-12B, and GATA6 were found to be hypomethylated in endometriotic tissue by several studies. In regards to histone modification, multiple studies reported that the acetylation levels of histones H3 and H4 affect multiple genes associated with endometriosis. In addition, HDAC2 was found to be elevated in endometriosis patients in two studies. Conclusion: Several studies reported a significant difference between specific genes' methylation levels in endometrial biopsies and normal tissue, which suggests that DNA methylation may play an important role in the modulation of the genotype in endometriotic tissue. Acetylation and methylation are the two key histone modifications leading to differential gene expression in endometriotic tissues. The alterations in gene expression reported by the 57 studies can have direct implications on cell cycle growth, cell cycle arrest, and apoptosis and, therefore, might play a key role in the pathogenesis of endometriosis. This review offers insight that histone modifications need further research to evaluate their role as potential biomarkers and treatment targets for endometriosis. Although several key similarities were reported, there were some disagreements among the results, which might be attributable to the heterogeneity between studies. Further research with a more robust standardization is needed to validate the epigenetic changes in endometriosis.

Clinical utility of endoscopic ultrasound-guided tissue acquisition for comprehensive genomic profiling of patients with biliary tract cancer, especially with intrahepatic cholangiocarcinoma.

BACKGROUND/AIMS: Endoscopic ultrasound-guided tissue acquisition (EUS-TA) is a standard diagnostic method for biliary tract cancer (BTC), and samples obtained in this manner may be used for comprehensive genomic profiling (CGP). This study evaluated the utility of EUS-TA for CGP in a clinical setting and determined the factors associated with the adequacy of CGP in patients with BTC. METHODS: CGP was attempted for 105 samples from 94 patients with BTC at the Aichi Cancer Center, Japan, from October 2019 to April 2022. RESULTS: Overall, 77.1% (81/105) of the samples were adequate for CGP. For 22-G or 19-G fine-needle biopsy (FNB), the sample adequacy was 85.7% (36/42), which was similar to that of surgical specimens (94%, p=0.45). Univariate analysis revealed that 22-G or larger FNB needle usage (86%, p=0.003), the target primary lesions (88%, p=0.015), a target size ≥30 mm (100%, p=0.0013), and number of punctures (90%, p=0.016) were significantly positively associated with CGP sample adequacy. CONCLUSIONS: EUS-TA is useful for CGP tissue sampling in patients with BTC. In particular, the use of 22-G or larger FNB needles may allow for specimen adequacy comparable to that of surgical specimens.

Genetic Profile of Rotavirus Type A in Children under 5 Years Old in Africa: A Systematic Review of Prevalence.

Human type A rotavirus (RV-A) is world-recognized as the major pathogen causing viral gastroenteritis in children under 5 years of age. The literature indicates a substantial increase in the diversity of rotavirus strains across continents, especially in Africa, which can pose significant challenges including an increase of disease burden and a reduction of vaccines' effectiveness. However, few studies have mapped the variety of circulating virus strains in different regions, which may hamper decisions on epidemiological surveillance and preventive public health measures. Thus, our aim was to compile the most updated available evidence on the genetic profile of RV-A among children in Africa and determine the prevalence of different genotypes according to the geographical regions by means of a broad systematic review. Systematic searches were performed in PubMed, Scopus, Web of Science, and Scielo without language, time limits, or geographical restrictions within the African continent. We selected full-text peer-reviewed articles assessing the genetic profile (i.e., genotyping) of RV-A in children up to 5 years old in Africa. Overall, 682 records were retrieved, resulting in 75 studies included for evidence synthesis. These studies were published between 1999 and 2022, were conducted in 28 countries from the five African regions, and 48% of the studies were carried out for 24 months or more. Most studies (n = 55; 73.3%) evaluated RV-A cases before the introduction of the vaccines, while around 20% of studies (n = 13) presented data after the vaccine approval in each country. Only seven (9.3%) studies compared evidence from both periods (pre- and post-vaccine introduction). Genotyping methods to assess RV-A varied between RT-PCR, nested or multiplex RT-PCR, testing only the most common P and G-types. We observed G1 and P[8] to be the most prevalent strains in Africa, with values around 31% and 43%, respectively. Yet if all the genotypes with the following highest prevalence were added ((G1 + G2, G3, G9) and (P[8] + P[6], P[4])), these figures would represent 80% and 99% of the total prevalence. The combination G1P[8] was the most reported in the studies (around 22%). This review study demonstrated an increased strain diversity in the past two decades, which could represent a challenge to the efficacy of the current vaccine.

Personalized Versus Precision Nanomedicine for Treatment of Ovarian Cancer.

The response to treatment is substantially varied between individual patients with ovarian cancer. However, chemotherapy treatment plans rarely pay sufficient attention to the mentioned factors. Instead, standardized treatment protocols are usually employed for most ovarian cancer patients. Variations in an individual's sensitivity to drugs significantly limit the effectiveness of treatment in some patients and lead to severe toxicities in others. In the present investigation, a nanotechnology-based approach for personalized treatment of ovarian carcinoma (the most lethal type of gynecological cancer) constructed on the individual genetic profile of the patient's tumor is developed and validated. The expression of predefined genes and proteins is analyzed for each patient sample. Finally, a mixture of the complex nanocarrier-based targeted delivery system containing drug(s)/siRNA(s)/targeted peptide is selected from the pre-synthesized bank and tested in vivo on murine cancer model using cancer cells isolated from tumors of each patient. Based on the results of the present study, an innovative approach and protocol for personalized treatment of ovarian cancer are suggested and evaluated. The results of the present study clearly show the advantages and perspectives of the proposed individual treatment approach.

Rapamycin as a Potential Alternative Drug for Squamous Cell Gingiva Carcinoma (Ca9-22): A Focus on Cell Cycle, Apoptosis and Autophagy Genetic Profile.

Oral cancer is considered as one of the most common malignancies worldwide. Its conventional treatment primarily involves surgery with or without postoperative adjuvant therapy. The targeting of signaling pathways implicated in tumorigenesis is becoming increasingly prevalent in the development of new anticancer drug candidates. Based on our recently published data, Rapamycin, an inhibitor of the mTOR pathway, exhibits selective antitumor activity in oral cancer by inhibiting cell proliferation and inducing cancer cell apoptosis, autophagy, and cellular stress. In the present study, our focus is on elucidating the genetic determinants of Rapamycin's action and the interaction networks accountable for tumorigenesis suppression. To achieve this, gingival carcinoma cell lines (Ca9-22) were exposed to Rapamycin at IC50 (10 µM) for 24 h. Subsequently, we investigated the genetic profiles related to the cell cycle, apoptosis, and autophagy, as well as gene-gene interactions, using QPCR arrays and the Gene MANIA website. Overall, our results showed that Rapamycin at 10 µM significantly inhibits the growth of Ca9-22 cells after 24 h of treatment by around 50% by suppression of key modulators in the G2/M transition, namely, Survivin and CDK5RAP1. The combination of Rapamycin with Cisplatin potentializes the inhibition of Ca9-22 cell proliferation. A P1/Annexin-V assay was performed to evaluate the effect of Rapamycin on cell apoptosis. The results obtained confirm our previous findings in which Rapamycin at 10 µM induces a strong apoptosis of Ca9-22 cells. The live cells decreased, and the late apoptotic cells increased when the cells were treated by Rapamycin. To identify the genes responsible for cell apoptosis induced by Rapamycin, we performed the RT2 Profiler PCR Arrays for 84 apoptotic genes. The blocked cells were believed to be directed towards cell death, confirmed by the downregulation of apoptosis inhibitors involved in both the extrinsic and intrinsic pathways, including BIRC5, BNIP3, CD40LG, DAPK1, LTA, TNFRSF21 and TP73. The observed effects of Rapamycin on tumor suppression are likely to involve the autophagy process, evidenced by the inhibition of autophagy modulators (TGFß1, RGS19 and AKT1), autophagosome biogenesis components (AMBRA1, ATG9B and TMEM74) and autophagy byproducts (APP). Identifying gene-gene interaction (GGI) networks provided a comprehensive view of the drug's mechanism and connected the studied tumorigenesis processes to potential functional interactions of various kinds (physical interaction, co-expression, genetic interactions etc.). In conclusion, Rapamycin shows promise as a clinical agent for managing Ca9-22 gingiva carcinoma cells.

Morphologic, phenotypic, and genotypic similarities between primary tumors and corresponding 3D cell cultures grown in a repeatable system-preliminary results.

BACKGROUND: Three-dimensional (3D) cell cultures are the new frontier for reproducing the tumor micro-environment in vitro. The aims of the study were (1) to establish primary 3D cell cultures from canine spontaneous neoplasms and (2) to demonstrate the morphological, phenotypic and genotypic similarities between the primary canine neoplasms and the corresponding 3D cultures, through the expression of tumor differentiation markers. RESULTS: Seven primary tumors were collected, including 4 carcinomas and 3 soft tissue sarcomas. 3D cell cultures reproduced the morphological features of the primary tumors and showed an overlapping immunophenotype of the primary epithelial tumors. Immunohistochemistry demonstrated the growth of stromal cells and macrophages admixed with the neoplastic epithelial component, reproducing the tumor microenvironment. Mesenchymal 3D cultures reproduced the immunophenotype of the primary tumor completely in 2 out of 3 examined cases while a discordant expression was documented for a single marker in one case. No single nucleotide variants or small indel were detected in TP53 or MDM2 genes, both in primary tumors and in 3D cell cultures specimens. In one sample, MDM2 amplicons were preferentially increased in number compared to TP53 ones, indicating amplification of MDM2, detectable both in the primary tumor and in the corresponding cell culture specimen. CONCLUSION: Here we demonstrate a good cell morphology, phenotype and genetic profile overlap between primary tumors and the corresponding 3D cultures grown in a repeatable system.

Advances in diffuse glial tumors diagnosis / Avanços no diagnóstico dos gliomas difusos

Abstract In recent decades, there have been significant advances in the diagnosis of diffuse gliomas, driven by the integration of novel technologies. These advancements have deepened our understanding of tumor oncogenesis, enabling a more refined stratification of the biological behavior of these neoplasms. This progress culminated in the fifth edition of the WHO classification of central nervous system (CNS) tumors in 2021. This comprehensive review article aims to elucidate these advances within a multidisciplinary framework, contextualized within the backdrop of the new classification. This article will explore morphologic pathology and molecular/genetics techniques (immunohistochemistry, genetic sequencing, and methylation profiling), which are pivotal in diagnosis, besides the correlation of structural neuroimaging radiophenotypes to pathology and genetics. It briefly reviews the usefulness of tractography and functional neuroimaging in surgical planning. Additionally, the article addresses the value of other functional imaging techniques such as perfusion MRI, spectroscopy, and nuclear medicine in distinguishing tumor progression from treatment-related changes. Furthermore, it discusses the advantages of evolving diagnostic techniques in classifying these tumors, as well as their limitations in terms of availability and utilization. Moreover, the expanding domains of data processing, artificial intelligence, radiomics, and radiogenomics hold great promise and may soon exert a substantial influence on glioma diagnosis. These innovative technologies have the potential to revolutionize our approach to these tumors. Ultimately, this review underscores the fundamental importance of multidisciplinary collaboration in employing recent diagnostic advancements, thereby hoping to translate them into improved quality of life and extended survival for glioma patients.

Resumo Nas últimas décadas, houve avanços significativos no diagnóstico de gliomas difusos, impulsionados pela integração de novas tecnologias. Esses avanços aprofundaram nossa compreensão da oncogênese tumoral, permitindo uma estratificação mais refinada do comportamento biológico dessas neoplasias. Esse progresso culminou na quinta edição da classificação da OMS de tumores do sistema nervoso central (SNC) em 2021. Esta revisão abrangente tem como objetivo elucidar esses avanços de forma multidisciplinar, no contexto da nova classificação. Este artigo irá explorar a patologia morfológica e as técnicas moleculares/genéticas (imuno-histoquímica, sequenciamento genético e perfil de metilação), que são fundamentais no diagnóstico, além da correlação dos radiofenótipos da neuroimagem estrutural com a patologia e a genética. Aborda sucintamente a utilidade da tractografia e da neuroimagem funcional no planejamento cirúrgico. Destacaremos o valor de outras técnicas de imagem funcional, como ressonância magnética de perfusão, espectroscopia e medicina nuclear, na distinção entre a progressão do tumor e as alterações relacionadas ao tratamento. Discutiremos as vantagens das diferentes técnicas de diagnóstico na classificação desses tumores, bem como suas limitações em termos de disponibilidade e utilização. Além disso, os crescentes avanços no processamento de dados, inteligência artificial, radiômica e radiogenômica têm grande potencial e podem em breve exercer uma influência substancial no diagnóstico de gliomas. Essas tecnologias inovadoras têm o potencial de revolucionar nossa abordagem a esses tumores. Em última análise, esta revisão destaca a importância fundamental da colaboração multidisciplinar na utilização dos recentes avanços diagnósticos, com a esperança de traduzi-los em uma melhor qualidade de vida e uma maior sobrevida.

Higher Prevalence of Nonsense Pathogenic DMD Variants in a Single-Center Cohort from Brazil: A Genetic Profile Study That May Guide the Choice of Disease-Modifying Treatments.

Dystrophinopathies are muscle diseases caused by pathogenic variants in DMD, the largest gene described in humans, representing a spectrum of diseases ranging from asymptomatic creatine phosphokinase elevation to severe Duchenne muscular dystrophy (DMD). Several therapeutic strategies are currently in use or under development, each targeting different pathogenic variants. However, little is known about the genetic profiles of northeast Brazilian patients with dystrophinopathies. We describe the spectrum of pathogenic DMD variants in a single center in northeast Brazil. This is an observational, cross-sectional study carried out through molecular-genetic analysis of male patients diagnosed with dystrophinopathies using Multiplex Ligation-dependent Probe Amplification (MLPA) followed by Next-Generation Sequencing (NGS)-based strategies. A total of 94 male patients were evaluated. Deletions (43.6%) and duplications (10.6%) were the most recurring patterns of pathogenic variants. However, small variants were present in 47.1% of patients, most of them nonsense variants (27.6%). This is the largest South American single-center case series of dystrophinopathies to date. We found a higher frequency of treatment-amenable nonsense single-nucleotide variants than most previous studies. These findings may have implications for diagnostic strategies in less-known populations, as a higher frequency of nonsense variants may mean a higher possibility of treating patients with disease-modifying drugs.

GPX3 Variant Genotype Affects the Risk of Developing Severe Forms of COVID-19.

In SARS-CoV-2 infection, excessive activation of the immune system intensively increases reactive oxygen species levels, causing harmful hyperinflammatory and oxidative state cumulative effects which may contribute to COVID-19 severity. Therefore, we assumed that antioxidant genetic profile, independently and complemented with laboratory markers, modulates COVID-19 severity. The study included 265 COVID-19 patients. Polymorphism of GSTM1, GSTT1, Nrf2 rs6721961, GSTM3 rs1332018, GPX3 rs8177412, GSTP1 rs1695, GSTO1 rs4925, GSTO2 rs156697, SOD2 rs4880 and GPX1 rs1050450 genes was determined with appropriate PCR-based methods. Inflammation (interleukin-6, CRP, fibrinogen, ferritin) and organ damage (urea, creatinine, transaminases and LDH) markers, complete blood count and coagulation status (d-dimer, fibrinogen) were measured. We found significant association for COVID-19 progression for patients with lymphocytes below 1.0 × 109/L (OR = 2.97, p = 0.002). Increased IL-6 and CRP were also associated with disease progression (OR = 8.52, p = 0.001, and OR = 10.97, p < 0.001, respectively), as well as elevated plasma AST and LDH (OR = 2.25, p = 0.021, and OR = 4.76, p < 0.001, respectively). Of all the examined polymorphisms, we found significant association with the risk of developing severe forms of COVID-19 for GPX3 rs8177412 variant genotype (OR = 2.42, p = 0.032). This finding could be of particular importance in the future, complementing other diagnostic tools for prediction of COVID-19 disease course.

Healthy lifestyle and genomic ancestry related to good glycemic control in type 1 diabetes patients from Northeastern Brazil: a hierarchical analysis.

Introduction: This study aimed to investigate the sociodemographic factors, dietary adherence, regular physical activity, and genomic ancestry percentage associated with good glycemic control in Brazilian patients with type 1 diabetes (T1D) using a hierarchical approach. Methods: A cross-sectional study was conducted in 152 T1D patients. Glycated hemoglobin (HbA1C) levels were measured to evaluate the glycemic control status (good, moderate, or poor). Independent factors included sex, age, self-reported skin color, educational level, family income, dietary patterns, and physical activity. The percentage of genomic ancestry (Native American, European, and African) was influenced by a panel of 46 autosomal insertion/deletion ancestry markers. Statistical analyses included receiver operating characteristic curves, and hierarchical logistic regression analysis. Results: The hierarchical analysis, patients who had high dietary adherence showed a positive association with good glycemic control (adjustedOR = 2.56, 95% CI:1.18-5.59, P = 0.016). Thus, age greater than 40 years was associated with good glycemic control compared to the children and adolescents group (adjustedOR = 4.55, 95% CI:1.14-18.1, P = 0.031). Males were associated with good glycemic control (adjustedOR = 2.00, 95% CI:1.01-4.00, P =0.047). Conclusion: The study findings suggest that consistent adherence to dietary regimens is associated with good glycemic control after adjusting for sociodemographic and genomic ancestry factors in an admixed population of T1D patients from Northeast Brazil.

Distinguished biological adaptation architecture aggravated population differentiation of Tibeto-Burman-speaking people.

Tibeto-Burman (TB) people have endeavored to adapt to the hypoxic, cold, and high-UV high-altitude environments in the Tibetan Plateau and complex disease exposures in lowland rainforests since the late Paleolithic period. However, the full landscape of genetic history and biological adaptation of geographically diverse TB-speaking people, as well as their interaction mechanism, remain unknown. Here, we generate a whole-genome meta-database of 500 individuals from 39 TB-speaking populations and present a comprehensive landscape of genetic diversity, admixture history, and differentiated adaptative features of geographically different TB-speaking people. We identify genetic differentiation related to geography and language among TB-speaking people, consistent with their differentiated admixture process with incoming or indigenous ancestral source populations. A robust genetic connection between the Tibetan-Yi corridor and the ancient Yellow River people supports their Northern China origin hypothesis. We finally report substructure-related differentiated biological adaptative signatures between highland Tibetans and Loloish speakers. Adaptative signatures associated with the physical pigmentation (EDAR and SLC24A5) and metabolism (ALDH9A1) are identified in Loloish people, which differed from the high-altitude adaptative genetic architecture in Tibetan. TB-related genomic resources provide new insights into the genetic basis of biological adaptation and better reference for the anthropologically informed sampling design in biomedical and genomic cohort research.

Dopamine multilocus genetic profile influence on reward network in chronic insomnia disorder with depression.

BACKGROUND: Chronic insomnia disorder (CID) is frequently comorbid with depression, and both conditions are believed to involve disruptions in the reward network. However, the potential effects of genetic polymorphisms in modulating this network remain largely unexplored. METHODS: In this study, we recruited 50 CID patients with high (CID-HD) and low (CID-LD) depressive symptoms and assessed their reward networks using resting-state functional MRI. Additionally, we calculated the multilocus genetic profile score (MGPS) to examine the influence of depression and dopamine genetic variation on the nucleus accumbens functional connectivity (NAFC) network in CID patients. RESULTS: Although the MGPS did not show a significant difference between the two CID groups, its influence on the NAFC network was observed in the salience network (SN) and visual network (VN) in CID patients. When comparing CID-HD patients to CID-LD patients, we found that CID-HD patients exhibited decreased NAFC in the internal reward network, default mode network, SN, and sensorimotor network, while showing increased NAFC in the executive control network (ECN) and VN. Furthermore, the influence of MGPS on the reward network was only significant in CID-HD patients, specifically in the internal reward network and ECN. CONCLUSION: These findings suggest that genetic variations related to dopamine may modulate the reward network differently in CID patients with and without depressive symptoms. These results contribute to our understanding of the pathophysiology of polygenic effects underlying brain network abnormalities in CID patients with depression.

TERT promoter mutation positive oral cavity carcinomas, a clinically and genetically distinct subgroup of head and neck squamous cell carcinomas.

BACKGROUNDS: The importance of TERT promoter (pTERT) mutation of oral cavity squamous cell carcinoma (OCSCC) with clinical features and genetic alterations are not well recognized. METHODS: We retrospectively analyzed genetic data from multiple databases, including 260 cases from the C-CAT database, 407 cases from the MSK-MetTropism database, and 40 OCSCC datasets from in-house clinical samples. RESULTS: From C-CAT database, TP53 (66%), CDKN2A (51%), and pTERT (29%) were the most frequent mutations observed. pTERT mutations were more prevalent in OCSCC (63%), younger individuals, and women (46%), with lower rates of alcohol abuse and smoking and co-mutated with TP53, HRAS, and CASP8. MSK-MetTroposim data validated with the enrichment of pTERT mutations in OCSCC, among women and Asian individuals. In-house datasets OCSCC with pTERT mutation (50%) characterized by fewer recurrent neck metastases. CONCLUSION: The study suggests that OCSCC with pTERT mutation represents a distinct subgroup with unique clinical and genetic characteristics.

Unraveling crime scenes strand by strand: the forensic odyssey of Bruce Budowle.

Bruce Budowle speaks to Ashling Cannon, Journal Development Editor for BioTechniques, about advancements & challenges in forensic science. Budowle completed his doctorate in genetics at Virginia Tech (VA, USA) formally known as Virginia Polytechnic Institute and State University. He then went on to complete a postdoctoral fellowship at the University of Alabama at Birmingham (AL, USA) to study genetic risk factors for acute lymphocytic leukemia, diabetes and melanoma. Budowle was early in his career and hadn't spent much time in forensics at this stage, but in 1982 an advert caught his eye for a job with the FBI to develop genetic marker systems to identify people who have left biological evidence at crime scenes. Budowle spent 26 years with the FBI and helped develop a plethora of genetic analysis methods. In 1985, it became a reality that DNA could be a signature for identifying people, and there were huge developments in DNA forensic analysis. In 2009, Budowle moved into academia and went to the University of North Texas Health Science Center (TX, USA), eventually becoming the Director of the Center for Human Identification, where he oversaw missing person and traditional crime cases, taught students and carried out fundamental and applied research. Budowle feels incredibly lucky to have had the resources, opportunities and academic infrastructure to learn and develop his knowledge. Budowle recently retired from academia and now spends his time building capacity for DNA forensics applications in Africa through the Department of Justice, with a well-established program known as the International Criminal Investigative Training Assistance Program (ICITAP) as well as with the non-government organization (NGO) DNAforAfrica.

Multilocus Genetic Profile Reflecting Low Dopaminergic Signaling Is Directly Associated with Obesity and Cardiometabolic Disorders Due to Antipsychotic Treatment.

Treatment with second-generation antipsychotics (SGAs) can cause obesity and other cardiometabolic disorders linked to D2 receptor (DRD2) and to genotypes affecting dopaminergic (DA) activity, within reward circuits. We explored the relationship of cardiometabolic alterations with single genetic polymorphisms DRD2 rs1799732 (NG_008841.1:g.4750dup -> C), DRD2 rs6277 (NG_008841.1:g.67543C>T), COMT rs4680 (NG_011526.1:g.27009G>A), and VNTR in both DRD4 NC_000011.10 (637269-640706) and DAT1 NC_000005.10 (1392794-1445440), as well as with a multilocus genetic profile score (MLGP). A total of 285 psychiatric patients treated with SGAs for at least three months were selected. Cardiometabolic parameters were classified according to ATP-III and WHO criteria. Blood samples were taken for routinely biochemical assays and PCR genotyping. Obesity (BMI, waist (W)), high diastolic blood pressure (DBP), and hypertriglyceridemia (HTG) were present in those genetic variants related to low dopaminergic activity: InsIns genotype in rs1799732 (BMI: OR: 2.91 [1.42-5.94]), DRD4-VNTR-L allele (W: OR: 1.73 [1.04-2.87]) and 9R9R variant in DAT1-VNTR (W: OR: 2.73 [1.16-6.40]; high DBP: OR: 3.33 [1.54-7.31]; HTG: OR: 4.38 [1.85-10.36]). A low MLGP score indicated a higher risk of suffering cardiometabolic disorders (BMI: OR: 1.23 [1.05-1.45]; W: OR: 1.18 [1.03-1.34]; high DBP: OR: 1.22 [1.06-1.41]; HTG: OR: 1.20 [1.04-1.39]). The MLGP score was more sensitive for detecting the risk of suffering these alterations. Low dopaminergic system function would contribute to increased obesity, BDP, and HTG following long-term SGA treatment.

Recent Progress and Challenges in the Development of Edible Vaccines Produced by Genetically Modified Plants.

Biotechnologists have pioneered the idea of an edible vaccination in recent years. Subunit vaccines, such as those used to create edible vaccines, involve the introduction of certain genes into transgenic plants, which are subsequently coaxed into producing the corresponding protein. Bananas, potatoes, legumes, lettuce, soybeans, corn, and rice are all examples of foods that fall under this category. They have a low unit cost, can be stored conveniently, and are simple to administer to patients of varying ages. There is great hope that the use of edible vaccinations, particularly in underdeveloped countries, could drastically reduce the prevalence of diseases, including measles, cholera, hepatitis B, and diarrhea. The development of effective and widely applicable edible vaccination, however, faces a number of technological and regulatory hurdles. When compared to traditional immunizations, edible vaccines offer significant cost savings, increased productivity, and reduced risk. It raises the possibility of a more efficient approach to illness prevention. This article includes important uses, production, host plants, benefits, drawbacks, mechanism of action, and many regulatory difficulties related to edible vaccines. In this article, we have discussed the most recent developments and successes with edible and intradermal vaccines in terms of the system used for immunogen production, the molecular properties of these vaccines, and their ability to generate a protective systemic and mucosal response.

Genetic alterations of KRAS and TP53 in intrahepatic cholangiocarcinoma associated with poor prognosis.

The aim of this study is to investigate certain genetic features of intrahepatic cholangiocarcinoma (ICCA). A total of 12 eligible ICCA patients were enrolled, and tumor tissues from the patients were subjected to next-generation sequencing of a multi-genes panel. Tumor mutation burden (TMB), mutated genes, copy number variants (CNVs), and pathway enrichment analysis were performed. The median TMB was 2.76 Mutation/Mb (range, 0-36.62 Mutation/Mb) in ICCA patients. The top two most commonly mutated genes in ICCA were KRAS (33%) and TP53 (25%). The co-mutations of KRAS and TP53 were 16.7% (2/12) in ICCA patients. Notably, patient P6 with the highest TMB did not have KRAS and TP53 mutations. Additionally, TP53 and/or KRAS alterations were significantly associated with poor progression-free survival than those with wild type (1.4 months vs 18 months). DNA damage repair and homologs recombinant repair deficiencies were significantly associated with high TMB in ICCA cases. In conclusion, we found that certain genetic mutations of TP53 and KRAS could predict poor prognosis in ICCA patients.