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In this study, we investigated the influence of quasi-one-dimensional (Quasi-1D) characteristics on the source and drain contact resistances within vertical nanowire (NW) field-effect transistors (FETs) of diminutive diameter. The top contact of the NW is segregated into two distinct regions: the first encompassing the upper surface, designated as the axial contact, and the second encircling the side surface, known as the radial contact, which is formed during the top-contact metal deposition process. Quantum confinement effects, prominent within Quasi-1D NWs, exert significant constraints on radial transport, consequently inducing a noticeable impact on contact resistance. Notably, in the radial direction, electron tunneling occurs only through quantized, discrete energy levels. Conversely, along the axial direction, electron tunneling freely traverses continuous energy levels. In a meticulous numerical analysis, these disparities in transport mechanisms unveiled that NWs with diameters below 30 nm exhibit a markedly higher radial contact resistance compared to their axial counterparts. Furthermore, an increase in the overlap length (less than 5 nm) contributes to a modest reduction in radial resistance; however, it remains consistently higher than the axial contact resistance.
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The negative impact of student-to-teacher victimization on teachers' perceptions of the work environment and their well-being is supported by growing empirical literature. For instance, violence in the classroom can have a negative impact on teachers themselves and hinder teachers from playing crucial roles in students' classroom experiences, resulting in adverse effects on student performance. However, the research field is limited in understanding the adverse effects on teachers' perceptions more directly related to student learning, such as teacher neglect. To fill the gap in the literature, the current study analyzes data from a nationwide sample of 1,054 middle and high school teachers in South Korea where teachers are generally treated with high regard and social status, often exerting a strong influence and authority over students in both an educational and parental way. Specifically, we conduct propensity score matching to investigate potential influences that student-to-teacher victimization can have on the following three outcome variables: teacher neglect, commitment, and pride. Results of mean comparisons after accounting for other confounding factors show that when compared with nonvictims, victims of student-to-teacher victimization are more likely to neglect their students; these victims also tend to exhibit less pride as teachers. Yet, the results also showed no significant statistical difference in teacher commitment. The current findings highlight the importance of developing programs to prevent and intervene in students' aggressive behaviors toward teachers. Particularly, administrators are recommended to consider providing training for teachers, specific to understanding student-to-teacher victimization in order to promote a more positive school environment and better student-to-teacher relationships in classrooms, including improving teachers' job performance.
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Colorectal cancer (CRC) ranks among the three most common cancers in Guam (GU), Hawai'i (HI), and the mainland United States (US). CRC prevalence in these areas is high among Filipinos, and indigenous CHamorus and Native Hawaiians; however, data on these populations are frequently aggregated in epidemiological studies, which can mask true CRC disparities. We examined CRC cumulative incidence rates (CIRs) among CHamorus in GU, Filipinos in GU, HI, and the US, and Native Hawaiians in HI and the US. CRC CIRs were calculated for two age groups (20-49 years; early onset, and 50-79 years; senior) and four time periods (2000-2004, 2005-2009, 2010-2014, and 2015-2019), stratified by ethnicity, sex, and location. Data analyzed included all invasive CRC cases reported to the Surveillance, Epidemiology, and End Results 9-Registry (n = 166,666), the Hawai'i Tumor Registry (n = 10,760), and the Guam Cancer Registry (n = 698) between 2000 and 2019. Senior CIRs were highest in HI and lowest in GU throughout all time periods, with a downward trend observed for senior CIRs in the US and HI, but not GU. This downward trend held true for all ethnic groups, except for CHamorus in GU, females in GU, and females of CHamoru ethnicity in GU. In contrast, early onset CIRs increased across all locations, sexes, and ethnic groups, except for Filipinos in HI and males of Filipino ethnicity in HI. Our findings provide crucial insights for future research and policy development aimed at reducing the burden of CRC among indigenous populations.
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Neoplasias Colorretais , Havaiano Nativo ou Outro Ilhéu do Pacífico , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Neoplasias Colorretais/epidemiologia , Guam/epidemiologia , Havaí/epidemiologia , Incidência , Estados Unidos/epidemiologia , IdosoRESUMO
Expression quantitative trait loci (eQTL) analysis measures the contribution of genetic variation in gene expression on complex traits. Although this methodology has been used to examine gene regulation in numerous human tissues, eQTL research in solid tissues is relatively lacking. We conducted eQTL analysis on placentas collected from an East Asian population in an effort to identify gene regulatory mechanisms in this tissue. Placentas (n = 102) were collected at the time of cesarean delivery. mRNA was extracted, sequenced with NGS, and compared with matched maternal and fetal DNA arrays performed using maternal and neonatal cord blood. Linear regression modeling was performed using tensorQTL. Fine-mapping along with epigenomic annotation was used to select putative functional variants. We identified 2,703 coding genes that contained at least one eQTL with statistical significance (false discovery rate <0.05). After fine-mapping, we found 108 previously unreported eQTL variants with posterior inclusion probability >0.1. Of these, 19% were located in genomic regions with evidence from public placental epigenome suggesting that they may be functionally relevant. For example, variant rs28379289 located in the placenta-specific regulatory region changes the binding affinity of transcription factor leading to higher expression of LGALS3, which is known to affect placental function. This study expands the knowledge base of regulatory elements within the human placenta and identifies 108 previously unreported placenta eQTL signals, which are listed in our publicly available GMI eQTL database. Further studies are needed to identify and characterize genetic regulatory mechanisms that affect placental function in normal pregnancy and placenta-related diseases.
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População do Leste Asiático , Locos de Características Quantitativas , Feminino , Humanos , Recém-Nascido , Gravidez , Estudo de Associação Genômica Ampla , Placenta , Polimorfismo de Nucleotídeo Único/genética , Locos de Características Quantitativas/genéticaRESUMO
PURPOSE: Brain metastasis rarely occurs in soft tissue sarcoma (STS). Here, we present five cases of STS with brain metastases with genetic profiles. MATERIALS AND METHODS: We included five patients from Seoul National University Hospital who were diagnosed with STS with metastasis to the brain. Tissue from the brain metastasis along with that from the primary site or other metastases were used for DNA and RNA sequencing to identify genetic profiles. Gene expression profiles were compared with sarcoma samples from The Cancer Genome Atlas. RESULTS: The overall survival after diagnosis of brain metastasis ranged from 2.2 to 34.3 months. Comparison of mutational profiles between brain metastases and matched primary or other metastatic samples showed similar profiles. In two patients, copy number variation profiles between brain metastasis and other tumors showed several differences including MYCL, JUN, MYC, and DDR2 amplification. Gene ontology analysis showed that the group of genes significantly highly expressed in the brain metastasis samples was enriched in the G-protein coupled receptor activity, structural constituent of chromatin, protein heterodimerization activity, and binding of DNA, RNA, and protein. Gene set enrichment analysis showed enrichment in the pathway of neuroactive ligand-receptor interaction and systemic lupus erythematosus. CONCLUSION: The five patients had variable ranges of clinical courses and outcomes. Genomic and transcriptomic analysis of STS with brain metastasis implicates possible involvement of complex expression modification and epigenetic changes rather than the addition of single driver gene alteration.
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Neoplasias Encefálicas , Sarcoma , Neoplasias de Tecidos Moles , Humanos , Variações do Número de Cópias de DNA , Sarcoma/genética , Sarcoma/patologia , Neoplasias de Tecidos Moles/patologia , Genômica , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/secundário , Perfilação da Expressão Gênica , DNARESUMO
CONTEXT: Rotator cuff tear is one of the most common causes of shoulder pain and has become a prominent disease most frequently treated by surgery. OBJECTIVES: To investigate the long-term therapeutic effect of integrative Korean medicine (KM) as a conservative treatment in treating rotator cuff tears. DESIGN: A multicenter observational study. SETTINGS: The settings involve four regional network KM hospitals. PATIENTS: The study participants are 288 patients aged 19-70 with rotator cuff tear identified by radiologist based on magnetic resonance imaging who received integrative KM treatment for the chief complaint of shoulder pain between 1 January 2015 and 31 March 2020. INTERVENTION: None. MAIN OUTCOMES: The primary outcome was the pain score in the affected shoulder, measured by the numeric rating scale (NRS). The secondary outcomes were Shoulder Pain and Disability Index (SPADI), 5-Level Quality of life: EuroQol 5-Dimension (EQ-5D-5L), Patient Global Impression of Change (PGIC), and range of motion (ROM) scores. RESULTS: Eligible patients for MCID achievement analysis for minimally clinical important change were 167, and 109 completed the follow-up survey. The mean NRS pain score in the affected shoulder was 5.80 ± 1.27 at admission, 3.50 ± 1.32 at discharge, and 3.83 ± 2.04 at follow-up.The mean SPADI score was 51.48 ± 20.18 at admission, 37.76 ± 19.23 at discharge, and 24.26 ± 21.80 at follow-up. The improvement at discharge (P-value < 0.001) and follow-up (P-value < 0.001) compared to those at admission was statistically significant. The results also presented a significant improvement in ROM for all motions at discharge after treatment (P-value < 0.001). The number of patients who achieved minimal clinically important difference in NRS was 116 (69.5%) at discharge and 71 (65.1%) at follow-up, and in SPADI was 82 (50.9%) at discharge and 77 (70.6%) at follow-up. CONCLUSION: The results of this study suggested that integrative KM treatment can help improve pain, functional impairment, QoL, and ROM in patients with a rotator cuff tear TRIAL REGISTRATION: NCT04566939.
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Lesões do Manguito Rotador , Humanos , Seguimentos , Pacientes Internados , Qualidade de Vida , Amplitude de Movimento Articular , República da Coreia , Estudos Retrospectivos , Manguito Rotador/patologia , Manguito Rotador/cirurgia , Lesões do Manguito Rotador/cirurgia , Dor de Ombro/terapia , Inquéritos e Questionários , Resultado do Tratamento , Adulto Jovem , Adulto , Pessoa de Meia-Idade , IdosoRESUMO
We present an in-depth single-cell atlas of in vitro multiculture systems on human primary airway epithelium derived from normal and diseased lungs of 27 individual donors. Our large-scale single-cell profiling identified new cell states and differentiation trajectories of rare airway epithelial cell types in human distal lungs. By integrating single-cell datasets of human lung tissues, we discovered immune-primed subsets enriched in lungs and organoids derived from patients with chronic respiratory disease. To demonstrate the full potential of our platform, we further illustrate transcriptomic responses to various respiratory virus infections in vitro airway models. Our work constitutes a single-cell roadmap for the cellular and molecular characteristics of human primary lung cells in vitro and their relevance to human tissues in vivo.
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Células Epiteliais , Pulmão , Humanos , Células Epiteliais/metabolismo , Epitélio , Diferenciação Celular/fisiologia , OrganoidesRESUMO
Underrepresentation of non-European (EUR) populations hinders growth of global precision medicine. Resources such as imputation reference panels that match the study population are necessary to find low-frequency variants with substantial effects. We created a reference panel consisting of 14,393 whole-genome sequences including more than 11,000 Asian individuals. Genome-wide association studies were conducted using the reference panel and a population-specific genotype array of 72,298 subjects for eight phenotypes. This panel yields improved imputation accuracy of rare and low-frequency variants within East Asian populations compared with the largest reference panel. Thirty-nine previously unidentified associations were found, and more than half of the variants were East Asian specific. We discovered genes with rare protein-altering variants, including LTBP1 for height and GPR75 for body mass index, as well as putative regulatory mechanisms for rare noncoding variants with cell type-specific effects. We suggest that this dataset will add to the potential value of Asian precision medicine.
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População do Leste Asiático , Estudo de Associação Genômica Ampla , Humanos , Genoma Humano , Polimorfismo de Nucleotídeo Único , Genótipo , Receptores Acoplados a Proteínas G/genéticaRESUMO
BACKGROUND: Compared to the U.S. population, cervical cancer (CC) incidence is significantly higher among the CHamoru, Micronesian, and Caucasian populations in Guam. From 2008-2012, CC was the fifth most common cancer diagnosed on the island. Despite the prevalence of CC and low HPV vaccine uptake, there is a concerning lack of awareness and preventative behavior among young adults. This study was aimed at influencing college students' knowledge and awareness of CC, CC screening, HPV, and the HPV vaccination. METHODS: We delivered a 30-minute educational intervention to a sample of 108 university students in a classroom setting. The effect of the educational intervention was measured through a pre-and post-test on CC and HPV health behaviors, knowledge, and awareness. Results were analyzed using SPSS and an exact McNemar's test was used to examine the difference in the proportion of correct answers to the tests. Two-way mixed ANOVA was used to examine between (gender, ethnicity, and class level) and within subjects (pre-and post-test) program effects. RESULTS: Of the 108 participants, only 39 (36.1%) reported being vaccinated for HPV, 23 (21.3%) had not been vaccinated, and 46 (42.6%) did not know if they had been vaccinated for HPV. Only forty-one (60.3%) female participants had had a Pap smear. When comparing the pre-to-posttest responses, most questions had an increase in correct responses. Time also influenced CCA and HPV knowledge and awareness scores as there was a significant increase in scores from the pre- to post-test. CONCLUSION: The educational intervention was an effective tool for increasing knowledge and awareness of CC, HPV, and HPV vaccination among college students. While study results demonstrate the educational intervention's success as a baseline measure of knowledge, the inclusion of behavioral outcome measures, such as intent to get vaccinated or screened, could result in more robust future studies.
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Infecções por Papillomavirus , Neoplasias do Colo do Útero , Adulto Jovem , Feminino , Humanos , Masculino , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/prevenção & controle , Guam , Infecções por Papillomavirus/prevenção & controle , Estudantes , EscolaridadeRESUMO
BACKGROUND: Although single-cell RNA sequencing of xenograft samples has been widely used, no comprehensive bioinformatics pipeline is available for human and mouse mixed single-cell analyses. Considering the numerous homologous genes across the human and mouse genomes, misalignment errors should be evaluated, and a new algorithm is required. We assessed the extents and effects of misalignment errors and exonic multi-mapping events when using human and mouse combined reference data and developed a new bioinformatics pipeline with expression-based species deconvolution to minimize errors. We also evaluated false-positive signals presumed to originate from ambient RNA of the other species and address the importance to computationally remove them. RESULT: Error when using combined reference account for an average of 0.78% of total reads, but such reads were concentrated to few genes that were greatly affected. Human and mouse mixed single-cell data, analyzed using our pipeline, clustered well with unmixed data and showed higher k-nearest-neighbor batch effect test and Local Inverse Simpson's Index scores than those derived from Cell Ranger (10 × Genomics). We also applied our pipeline to multispecies multisample single-cell library containing breast cancer xenograft tissue and successfully identified all samples using genomic array and expression. Moreover, diverse cell types in the tumor microenvironment were well captured. CONCLUSION: We present our bioinformatics pipeline for mixed human and mouse single-cell data, which can also be applied to pooled libraries to obtain cost-effective single-cell data. We also address misalignment, multi-mapping error, and ambient RNA as a major consideration points when analyzing multispecies single-cell data.
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Biologia Computacional , Genoma , Algoritmos , Animais , Genômica , Humanos , Camundongos , RNARESUMO
Although some studies have focused on immigrants' fear of crime in the United States, it is important to point out that the number of North Korean defectors to South Korea has rapidly increased since the 1990s. Therefore, understanding factors associated with fear of crime for North Korean immigrants, especially female defectors, is important for ensuring their successful transitions into South Korean culture. The present study used existing survey data from a sample of female North Korean defectors to explore factors related to fear of crime. Results indicate that the number of North Korean friends, language proficiency, and patriarchal attitudes toward gender were significant predictors of fear of crime for the North Korean female defectors. Findings are described and discussed as a potential source for policymaking to reduce North Korean immigrants' acculturative stress and fear of crime and to encourage smooth transitions into new cultures.
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Crime , Idioma , República Democrática Popular da Coreia , Medo , Feminino , Humanos , Masculino , República da CoreiaRESUMO
The role of routine activity theory (RAT) as a guiding theoretical approach to understand online victimization has been well documented. However, the recent emphasis in criminology on its applicability to online victimization has largely been based on evidence from Anglo-American studies. This study fills this gap by testing the predictive utility of RAT for cyberstalking victimization, using data from a sample of female Iranian students. Our structural equation model showed that online exposure to motivated offenders, target suitability, and ineffective online guardianship were positively and significantly associated with cyberstalking victimization. Our results provide strong support for RAT, indicating its generalizability to a different sociopolitical context.
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Bullying , Vítimas de Crime , Criminosos , Feminino , Humanos , Irã (Geográfico) , Masculino , EstudantesRESUMO
We investigated the molecular mechanisms of paclitaxel resistance in TNBC using seven patient-derived xenograft (PDX) models and TNBC cell lines. Among the seven PDX models, four models showed resistance to paclitaxel. Dysregulation of JAK/STAT pathways and JAK2 copy number gains were observed in the four paclitaxel-resistant PDX tumors. In TNBC cell lines, silencing the JAK2 gene showed a significant but mild synergistic effect when combined with paclitaxel in vitro. However, JAK1/2 inhibitor treatment resulted in restoration of paclitaxel sensitivity in two out of four paclitaxel-resistant PDX models and JAK1/2 inhibitor alone significantly suppressed the tumor growth in one out of the two remaining PDX models. Transcriptome data derived from the murine microenvironmental cells revealed an enrichment of genes involved in the cell cycle processes among the four paclitaxel-resistant PDX tumors. Histologic examination of those PDX tumor tissues showed increased Ki67-positive fibroblasts in the tumor microenvironment. Among the four different cancer-associated fibroblast (CAF) subtypes, cycling CAF exhibiting features of active cell cycle was enriched in the paclitaxel-resistant PDX tumors. Additionally, fibroblasts treated with the conditioned media from the JAK2-silenced breast cancer cells showed downregulation of cell cycle-related genes. Our data suggest that the JAK2 gene may play a critical role in determining responses of TNBC to paclitaxel by modulating the intrinsic susceptibility of cancer cells against paclitaxel and also by eliciting functional transitions of CAF subtypes in the tumor microenvironment. KEY MESSAGES : We investigated the molecular mechanisms of paclitaxel resistance in TNBC. JAK2 signaling was associated with paclitaxel resistance in TNBC PDX models. Paclitaxel-resistant PDX tumors were enriched with microenvironment cCAF subpopulation. JAK2 regulated paclitaxel-resistant CAF phenotype transition.
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Antineoplásicos Fitogênicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Janus Quinase 2/genética , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/genética , Paclitaxel/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Animais , Antineoplásicos Fitogênicos/farmacologia , Fibroblastos Associados a Câncer/metabolismo , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Janus Quinase 2/antagonistas & inibidores , Janus Quinase 2/metabolismo , Neoplasias Mamárias Experimentais/metabolismo , Camundongos , Nitrilas/farmacologia , Paclitaxel/farmacologia , Pirazóis/farmacologia , Pirimidinas/farmacologia , Neoplasias de Mama Triplo Negativas/metabolismo , Microambiente Tumoral/efeitos dos fármacosRESUMO
Gastric cancer (GC) is commonly treated by chemotherapy using 5-fluorouracil (5-FU) derivatives and platinum combination, but predictive biomarker remains lacking. We develop patient-derived xenografts (PDXs) from 31 GC patients and treat with a combination of 5-FU and oxaliplatin, to determine biomarkers associated with responsiveness. When the PDXs are defined as either responders or non-responders according to tumor volume change after treatment, the responsiveness of PDXs is significantly consistent with the respective clinical outcomes of the patients. An integrative genomic and transcriptomic analysis of PDXs reveals that pathways associated with cell-to-cell and cell-to-extracellular matrix interactions enriched among the non-responders in both cancer cells and the tumor microenvironment (TME). We develop a 30-gene prediction model to determine the responsiveness to 5-FU and oxaliplatin-based chemotherapy and confirm the significant poor survival outcomes among cases classified as non-responder-like in three independent GC cohorts. Our study may inform clinical decision-making when designing treatment strategies.
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Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Neoplasias Gástricas/tratamento farmacológico , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Adenocarcinoma/genética , Animais , Feminino , Fluoruracila/administração & dosagem , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos Endogâmicos NOD , Camundongos Knockout , Camundongos SCID , Oxaliplatina/administração & dosagem , Neoplasias Gástricas/genética , Análise de Sobrevida , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/genéticaRESUMO
BACKGROUNDMolecular characterization in pediatric papillary thyroid cancer (PTC), distinct from adult PTC, is important for developing molecularly targeted therapies for progressive radioiodine-refractory (131I-refractory) PTC.METHODSPTC samples from 106 pediatric patients (age range: 4.3-19.8 years; n = 84 girls, n = 22 boys) who were admitted to SNUH (January 1983-March 2020) were available for genomic profiling. Previous transcriptomic data from 125 adult PTC samples were used for comparison.RESULTSWe identified genetic drivers in 80 tumors: 31 with fusion oncogenes (RET in 21 patients, ALK in 6 patients, and NTRK1/3 in 4 patients); 47 with point mutations (BRAFV600E in 41 patients, TERTC228T in 2 patients [1 of whom had a coexisting BRAFV600E], and DICER1 variants in 5 patients); and 2 with amplifications. Fusion oncogene PTCs, which are predominantly detected in younger patients, were at a more advanced stage and showed more recurrent or persistent disease compared with BRAFV600E PTCs, which are detected mostly in adolescents. Pediatric fusion PTCs (in patients <10 years of age) had lower expression of thyroid differentiation genes, including SLC5A5, than did adult fusion PTCs. Two girls with progressive 131I-refractory lung metastases harboring a TPR-NTRK1 or CCDC6-RET fusion oncogene received fusion-targeted therapy; larotrectinib and selpercatinib decreased the size of the tumor and restored 125I radioiodine uptake. The girl with the CCDC6-RET fusion oncogene received 131I therapy combined with selpercatinib, resulting in a tumor response. In vitro 125I uptake and 131I clonogenic assays showed that larotrectinib inhibited tumor growth and restored radioiodine avidity.CONCLUSIONSIn pediatric patients with fusion oncogene PTC who have 131I-refractory advanced disease, selective fusion-directed therapy may restore radioiodine avidity and lead to a dramatic tumor response, underscoring the importance of molecular testing in pediatric patients with PTC.FUNDINGThe Ministry of Science, ICT and Future Planning (NRF-2016R1A2B4012417 and 2019R1A2C2084332); the Korean Ministry of Health and Welfare (H14C1277); the Ministry of Education (2020R1A6A1A03047972); and the SNUH Research Fund (04-2015-0830).TRIAL REGISTRATIONTwo patients received fusion-targeted therapy with larotrectinib (NCT02576431; NAVIGATE) or selpercatinib (LOXO-RET-18018).
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Terapia de Alvo Molecular/métodos , Proteínas Proto-Oncogênicas c-ret/genética , Receptor trkA/genética , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/terapia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/terapia , Adolescente , Fatores Etários , Criança , Pré-Escolar , Terapia Combinada , Feminino , Humanos , Radioisótopos do Iodo/farmacocinética , Radioisótopos do Iodo/uso terapêutico , Masculino , Proteínas de Fusão Oncogênica/genética , Proteínas Proto-Oncogênicas c-ret/antagonistas & inibidores , Pirazóis/uso terapêutico , Piridinas/uso terapêutico , Pirimidinas/uso terapêutico , Compostos Radiofarmacêuticos/farmacocinética , Compostos Radiofarmacêuticos/uso terapêutico , Receptor trkA/antagonistas & inibidores , Câncer Papilífero da Tireoide/radioterapia , Neoplasias da Glândula Tireoide/radioterapia , Transcriptoma , Adulto JovemRESUMO
Early life stress (ELS) is strongly associated with psychiatric disorders such as anxiety, depression, and schizophrenia in adulthood. To date, biological, behavioral, and structural aspects of ELS have been studied extensively, but their functional effects remain unclear. Here, we examined NeuroPET studies of dopaminergic, glutamatergic, and serotonergic systems in ELS animal models. Maternal separation and restraint stress were used to generate single or complex developmental trauma. Body weights of animals exposed to single trauma were similar to those of control animals; however, animals exposed to complex trauma exhibited loss of body weight when compared to controls. In behavioral tests, the complex developmental trauma group exhibited a decrease in time spent in the open arm of the elevated plus-maze and an increase in immobility time in the forced swim test when compared to control animals. In NeuroPET studies, the complex trauma group displayed a reduction in brain uptake values when compared to single trauma and control groups. Of neurotransmitter systems analyzed, the rate of decrease in brain uptake was the highest in the serotonergic group. Collectively, our results indicate that developmental trauma events induce behavioral deficits, including anxiety- and depressive-like phenotypes and dysfunction in neurotransmitter systems.
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Encéfalo/metabolismo , Encéfalo/fisiologia , Neurotransmissores/metabolismo , Ferimentos e Lesões/metabolismo , Ferimentos e Lesões/fisiopatologia , Animais , Animais Recém-Nascidos/metabolismo , Animais Recém-Nascidos/fisiologia , Ansiedade/metabolismo , Ansiedade/fisiopatologia , Transtornos de Ansiedade/metabolismo , Transtornos de Ansiedade/fisiopatologia , Comportamento Animal/fisiologia , Depressão/metabolismo , Depressão/fisiopatologia , Modelos Animais de Doenças , Comportamento Exploratório/fisiologia , Feminino , Masculino , Privação Materna , Aprendizagem em Labirinto/fisiologia , Imagem Molecular/métodos , Ratos , Ratos Sprague-Dawley , Estresse Psicológico/metabolismo , Estresse Psicológico/fisiopatologia , Natação/fisiologiaRESUMO
Playing through pain and injury is a common and accepted behavior in the athletic realm. The purpose of this research was to apply Tittle's control balance theory to explain why athletes engage in playing through pain and injury despite its risky nature. We hypothesized that playing through pain and injury is a form of submission described by Tittle and that it can be predicted by the concept of control deficit. To this end, we collected and used data from a sample of 410 professional soccer players from Guilan province, Iran, and tested several propositions derived from control balance theory. Hierarchical linear regression was used to analyze the data. The study findings demonstrate that players with more control deficits are more likely to play through pain and injury. This relationship is conditioned by self-control, opportunity, motivation, perceived benefits, and provocations. For example, the relationship between control deficit and playing through pain and injury is stronger for those with lower self-control. Our findings support the utility of control balance theory in explaining an act of submission (i.e., playing through pain and injury).
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Traumatismos em Atletas , Futebol , Atletas , Traumatismos em Atletas/epidemiologia , Humanos , Irã (Geográfico)/epidemiologia , Dor/epidemiologia , Fatores de RiscoRESUMO
The global incidence of early-onset colorectal cancer (EO-CRC) is rapidly rising. However, the reason for this rise in incidence as well as the genomic characteristics of EO-CRC remain largely unknown. We performed whole-exome sequencing in 47 cases of EO-CRC and targeted deep sequencing in 833 cases of CRC. Mutational profiles of EO-CRC were compared with previously published large-scale studies. EO-CRC and The Cancer Genome Atlas (TCGA) data were further investigated according to copy number profiles and mutation timing. We classified colorectal cancer into three subgroups: the hypermutated group consisted of mutations in POLE and mismatch repair genes; the whole-genome doubling group had early functional loss of TP53 that led to whole-genome doubling and focal oncogene amplification; the genome-stable group had mutations in APC and KRAS, similar to conventional colon cancer. Among non-hypermutated samples, whole-genome doubling was more prevalent in early-onset than in late-onset disease (54% vs 38%, Fisher's exact P = 0.04). More than half of non-hypermutated EO-CRC cases involved early TP53 mutation and whole-genome doubling, which led to notable differences in mutation frequencies between age groups. Alternative carcinogenesis involving genomic instability via loss of TP53 may be related to the rise in EO-CRC.
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Neoplasias Colorretais/patologia , Sequenciamento do Exoma/métodos , Genoma Humano , Mutação com Perda de Função , Instabilidade de Microssatélites , Proteína Supressora de Tumor p53/genética , Adulto , Idade de Início , Neoplasias Colorretais/genética , Feminino , Humanos , Masculino , Adulto JovemRESUMO
Emotional memory processing engages a large neuronal network of brain regions including the cerebellum. However, the molecular and cellular mechanisms of the cerebellar cortex modulating the fear memory network are unclear. Here, we illustrate that synaptic signaling in cerebellar Purkinje cells (PCs) via STAT3 regulates long-term fear memory. Transcriptome analyses revealed that PC-specific STAT3 knockout (STAT3PKO) results in transcriptional changes that lead to an increase in the expression of glutamate receptors. The amplitude of AMPA receptor-mediated excitatory postsynaptic currents at parallel fiber (PF) to PC synapses was larger in STAT3PKO mice than in wild-type (WT) littermates. Fear conditioning induced long-term depression of PF-PC synapses in STAT3PKO mice while the same manipulation induced long-term potentiation in WT littermates. STAT3PKO mice showed an aberrantly enhanced long-term fear memory. Neuronal activity in fear-related regions increased in fear-conditioned STAT3PKO mice. Our data suggest that STAT3-dependent molecular regulation in PCs is indispensable for proper expression of fear memory.
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Medo , Memória de Longo Prazo , Plasticidade Neuronal/genética , Células de Purkinje/metabolismo , Fator de Transcrição STAT3/genética , Animais , Masculino , Camundongos , Fator de Transcrição STAT3/deficiência , Fator de Transcrição STAT3/metabolismoRESUMO
Criminologists have long considered the extent to which victimization experiences influence fear of future victimization. As a result, some scholars have proposed risky lifestyles theory as a theoretical framework linking individuals' lifestyles and experiences to their fear of victimization. This study contributes to and extends this line of research by exploring whether risky lifestyles and prior victimization influence fear of future victimization among a large sample of incarcerated felons in South Korea. Results show that although risky lifestyles heighten fear of sexual assault and fear of property theft among inmates, risky lifestyles are not predictive of fear of violent assault. This finding expands the scope of risky lifestyles theory and provides an understanding of why fear of victimization occurs within the prison context.