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1.
PLoS One ; 19(2): e0296808, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38329987

RESUMO

PURPOSE: Since identified in December 2019, the novel coronavirus disease 2019 (COVID-19) has had a global impact on medical resource use and costs for patients with cancer in South Korea. This study aimed to identify the medical use and costs among patients with cancer during the COVID-19 pandemic, to predict these patterns in South Korea in the future. METHODS: We conducted a secondary claims data analysis using the National Health Insurance Service database for the calendar period of 2019-2020. Monthly relative percent changes in cancer incidence, medical use, and billing costs for medical care utilization by cancer type were calculated. Then, the medical use and costs after January 2020 were predicted using a time series model with data before the COVID-19 outbreak (2014-2019). RESULTS: The incidence of cancer diagnoses has seen a notable decline since the outbreak of the COVID-19 in 2020 as compared to 2019. Despite the impact of COVID-19, there hasn't been a distinct decline in outpatient utilization when compared to inpatient utilization. While medical expenses for both inpatient and outpatient visits have slightly increased, the number of patients treated for cancer has decreased significantly compared to the previous year. In June 2020, overall outpatient costs experienced the highest increase (21.1%), while individual costs showed the most significant decrease (-4.9%) in June 2020. Finally, the number of hospitalisations and outpatient visits increased slightly from June-July in 2020, reducing the difference between the actual and predicted values. The decrease in the number of inpatient hospitalisations (-22~-6%) in 2020 was also high. CONCLUSIONS: The overall use of medical services by patients with cancer decreased in 2020 compared with that in the pre-COVID-19 pandemic period. In the future, the government should consider how to recover from the COVID-19 pandemic, and establish permanent health policies for patients with cancer.


Assuntos
COVID-19 , Neoplasias , Humanos , Gastos em Saúde , Pandemias , COVID-19/epidemiologia , Custos e Análise de Custo , Hospitalização , Neoplasias/epidemiologia , Neoplasias/terapia , Estudos Retrospectivos
2.
Animals (Basel) ; 14(3)2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38338032

RESUMO

The bovine coronavirus (BCoV) KBR-1 strain, obtained from calf diarrhea samples collected in 2017, belongs to group GIIa. To attenuate this strain, it was subcultured continuously (up to 79 times) in HRT-18 cells, followed by 80-120 passages in MDBK cells. The KBR-1-p120 strain harvested from MDBK cells at passage 120 harbored 13 amino acid mutations in the spike gene. Additionally, the KBR-1-p120 strain showed a high viral titer and cytopathogenic effects in MDBK cells. Seven-day-old calves (negative for BCoV antigen and antibodies) that did not consume colostrum were orally inoculated with the attenuated candidate strain (KBR-1-p120), or with KBR-1 passaged 10 times (KBR-1-p10) in HRT-18 cells. Calves inoculated with KBR-1-p10 had a low diarrhea score, and BCoV RNA was detected at 3-7 days post-inoculation (DPI). The virus was also present in the duodenum, jejunum, and ileum at autopsy; however, calves inoculated with KBR-1-p120 had low levels of BCoV RNA in feces at 4-6 DPI, and no diarrhea. In addition, an extremely small amount of BCoV RNA was present in the jejunum and ileum at autopsy. The small intestines of calves inoculated with KBR-1-p120 were emulsified and used to infect calves two more times, but pathogenicity was not recovered. Therefore, the KBR-1-p120 strain has potential as a live vaccine candidate.

3.
Vaccine ; 41(49): 7377-7386, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-37973511

RESUMO

In several countries, classical swine fever (CSF) has not been detected in domestic pigs, but has been detected in wild boars, making the disease difficult to control. To overcome this problem, we inoculated pigs with a CSF live marker vaccine (Flc-LOM-BErns strain), which has "distinguish infection from vaccinated animals (DIVA)" function, to determine whether it is suitable as an oral vaccine specifically for wild boars. Pigs inoculated intramuscularly or orally with the Flc-LOM-BErns vaccine were challenged 2 or 4 weeks later, respectively, with virulent CSFV. Pigs administered the oral Flc-LOM-BErns strain (105.0 and 6.0 TCID50/dose), and those vaccinated intramuscularly (103.0 TCID50/dose), had normal numbers of leukocytes and normal body temperature. Also, they generated protective neutralizing antibodies and anti-BVDV Erns antibodies. In addition, all pigs in these groups survived, with no CSFV RNA detected in feces, spleen, or other organs. Thus, the Flc-LOM-BErns vaccine shows excellent safety and efficacy, while having DIVA function and suitability for oral inoculation.


Assuntos
Vírus da Febre Suína Clássica , Peste Suína Clássica , Vacinas Virais , Suínos , Animais , Peste Suína Clássica/prevenção & controle , Vacinas Marcadoras , Anticorpos Antivirais , Vacinas Atenuadas , Sus scrofa
4.
Viruses ; 15(11)2023 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-38005843

RESUMO

From late 2013-2022, 1131 cases of porcine epidemic diarrhea (PED) were reported to the Korean Animal Health Integrated System (KAHIS). There were four major outbreaks from winter to spring (2013-2014, 2017-2018, 2018-2019, and 2021-2022), with the main outbreaks occurring in Chungnam (CN), Jeonbuk (JB), and Jeju (JJ). Analysis of the complete spike (S) gene of 140/1131 KAHIS PEDV cases nationwide confirmed that 139 belonged to the G2b genotype and 1 to the G2a genotype. Among them, two strains (K17GG1 and K17GB3) were similar to an S INDEL isolated in the United States (strain OH851), and 12 strains had deletions (nucleotides (nt) 3-99) or insertions (12 nt) within the S gene. PEDVs in JJ formed a regionally independent cluster. The substitution rates (substitutions/site/year) were as follows: 1.5952 × 10-3 in CN, 1.8065 × 10-3 in JB, and 1.5113 × 10-3 in JJ. A Bayesian skyline plot showed that the effective population size of PEDs in JJ fell from 2013-2022, whereas in CN and JB it was maintained. Genotyping of 340 Korean PEDV strains, including the 140 PEDVs in this study and 200 Korean reference strains from GenBank, revealed that only the highly pathogenic non-INDEL type (G2b) was dominant from 2020 onwards. Therefore, it is predicted that the incidence of PED will be maintained by the G2b (non-INDEL) genotype.


Assuntos
Infecções por Coronavirus , Vírus da Diarreia Epidêmica Suína , Doenças dos Suínos , Suínos , Animais , Estados Unidos , Vírus da Diarreia Epidêmica Suína/genética , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/veterinária , Prevalência , Teorema de Bayes , Doenças dos Suínos/epidemiologia , República da Coreia/epidemiologia , Filogenia , Glicoproteína da Espícula de Coronavírus/genética , Diarreia
5.
Vaccines (Basel) ; 11(10)2023 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-37897024

RESUMO

A chimeric pestivirus (KD26_E2LOM) was prepared by inserting the E2 gene of the classical swine fever virus (CSFV) LOM strain into the backbone of the bovine viral diarrhea virus (BVDV) KD26 strain. KD26_E2LOM was obtained by transfecting the cDNA pACKD26_E2LOM into PK-15 cells. KD26_E2LOM chimeric pestivirus proliferated to titers of 106.5 TCID50/mL and 108.0 TCID50/mL at 96 h post-inoculation into PK-15 cells or MDBK cells, respectively. It also reacted with antibodies specific for CSFV E2 and BVDV Erns, but not with an anti-BVDV E2 antibody. Piglets (55-60 days old) inoculated with a high dose (107.0 TCID50/mL) of KD26_E2LOM produced high levels of CSFV E2 antibodies. In addition, no co-habiting pigs were infected with KD26_E2LOM; however, some inoculated pigs excreted the virus, and the virus was detected in some organs. When pregnant sows were inoculated during the first trimester (55-60 days) with a high dose (107.0 TCID50/mL) of KD26_E2LOM, anti-CSFV E2 antibodies were produced at high levels; chimeric pestivirus was detected in one fetus and in the ileum of one sow. When 5-day-old calves that did not consume colostrum received a high dose (107.0 TCID50/mL) of KD26_E2LOM, one calf secreted the virus in both feces and nasal fluid on Day 2. A high dose of KD26_E2LOM does not induce specific clinical signs in most animals, does not spread from animal to animal, and generates CSFV E2 antibodies with DVIA functions. Therefore, chimeric pestivirus KD26_E2LOM is a potential CSFV live marker vaccine.

6.
Uisahak ; 32(2): 553-591, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37718562

RESUMO

One of the most remarkable medical achievements of the Korean War was the development of psychiatry. During the Korean War, soldiers and prisoners of war (POWs) experienced "gross stress reaction" and manifested poor concentration and memory as well as clinical depression and social alienation. Rest and relaxation rotations served as the primary treatment for their conditions. Civilians also bore the brunt of the war's effects. Delusions of grandeur and megalomania appear to have been common among Koreans, but there were few mental health facilities to provide treatment and care. Out of the furnace of war, psychiatry emerged as a newly specialized field, and in the 1950s, Korea became the very place where military psychiatry training under the U.S. military laid the groundwork for civilian psychiatry. This essay aims to enrich the study of mental illness during and after the Korean War by providing a more detailed picture of the mental problems experienced not only by veterans and POWs, but also by civilians in Korea. Examining mental health issues from this period is challenging due to the scarcity of resources for delving into the minds of the civilians involved. Taking military psychiatry as a starting point, this essay goes beyond existing scholarship to discuss psychiatry-related responses to the Korean War, including the influence of military psychiatry on civilian psychiatry, the endeavors of medical professionals and government policies, and contemporary expressions of mental distress during and after the war.


Assuntos
Povo Asiático , Guerra da Coreia , Psiquiatria , Humanos , Povo Asiático/psicologia , Psiquiatria Militar , Medicina Militar , Militares/psicologia , Prisioneiros de Guerra/psicologia
7.
Animals (Basel) ; 13(14)2023 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-37508089

RESUMO

This study aimed to investigate the genetic diversity of G- and P-type bovine RVAs (BoRVAs) prevalent in Vietnam. Between 2017 and 2018, the prevalence of BoRVAs detected in diarrhea samples from 8 regions was as low as 1.9% (11/582). The prevalence of the G-type was 45.5% for G6 and 18.2% for G10; however, 36.3% remain unidentified. Interestingly, all BoRVAs were investigated as P[11], and there was no diversity within this P-type. Geographically, the G6 and G10 types were not identified in any specific area; rather, they occurred in both Northern and Southern Vietnam. G6P[11] and G10P[11], which are combined G- and P-types, were identified in 71.4% and 28.6% of BoRVA-positive samples, respectively. Phylogenetic tree analysis revealed that the G6-type detected in Vietnamese cows is similar to strains derived from China, Japan, and Korea, whereas the G10 type is closely related to the Chinese strain. In addition, the P11 strain detected in Vietnamese cows is similar to the Spanish and Chinese strains. The BoRVA-positive rate was higher in cows aged less than 2 months (3.2%, 3/94) than in those aged 2 months or more (1.6%, 8/488). In summary, we detected the presence of G6P11 and G10P11 BoVRAs on Vietnamese cow farms, and found that they were more predominant in young calves than in older cows.

8.
Viruses ; 15(7)2023 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-37515287

RESUMO

In South Korea in 2013, the G1-based vaccine failed to prevent an outbreak of G2b-type porcine epidemic diarrhea virus (PEDV), which is more pathogenic than the traditional G1-type strain, thereby allowing the virus to spread. In 2017 and 2018, field samples were cultured sequentially on Vero cells to isolate HS (virulent) and SGP-M1 (partially attenuated) strains, respectively, of the G2b type. The HS strain harbors a single amino acid (aa) change and two aa deletions in the N-terminal domain of S1 (55I56G57E→55K56Δ57Δ). The SGP-M1 strain harbors a seven aa deletion in the C-terminal domain of S2 (1380~1386ΔFEKVHVQ). By co-infecting various animal cells with these two strains (HS and SGP-M1), we succeeded in cloning strain HSGP, which harbors the mutations present in the two original viruses. The CPE pattern of the HSGP strain was different from that of the HS and SGP-M1 strains, with higher viral titers. Studies in piglets showed attenuated pathogenicity of the HSGP strain, with no clinical symptoms or viral shedding, and histopathologic lesions similar to those in negative controls. These findings confirm that deletion of specific sequences from the S gene attenuates the pathogenicity of PEDV. In addition, HSGP strains created by combining two different strains have the potential for use as novel attenuated live vaccine candidates.


Assuntos
Infecções por Coronavirus , Vírus da Diarreia Epidêmica Suína , Doenças dos Suínos , Chlorocebus aethiops , Suínos , Animais , Células Vero , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/veterinária , Vacinas Atenuadas/genética , Diarreia
9.
Infect Chemother ; 55(2): 237-246, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37407241

RESUMO

BACKGROUND: This study aimed to identify the trends in pharmaceutical expenditure (PE), share of PE in health expenditure (HE), and trends in expenditure by pharmacological groups (ATC level 1 classification) in Korea for a 10-year period (2011 - 2020) and compare the data with those of other Organisation for Economic Co-operation and Development (OECD) countries. Using the findings, we determined the current status of pharmaceutical expenditure (PE) management in Korea and derived the implications for establishing future macroscopic policies on PE. MATERIALS AND METHODS: We analyzed the OECD Health Statistics and the Korean national health insurance claims database from January 2011 through December 2020. The outcome measures were HE, PE, and pharmaceutical sales data for ATC level 1 medicines from OECD Health Statistics data during 2011 - 2020. As OECD collects limited ATC level 1 data, we used the HIRA health insurance claims data for PEs of ATC level-1 classification, including D, L, P, and S. RESULTS: PE in Korea increased by 38.5% from 19.9 billion USD in 2011 to 27.6 billion USD in 2020, whereas the share of PE in HE decreased by 6.3%p from 26.4% in 2011 to 20.1% in 2020. In 2020, Korea ranked third in PE per capita (760.9 USD PPP) and had the highest share of PE (20.1%) among the 19 OECD countries studied. By ATC level 1 class, the highest PE was A (alimentary tract and metabolism) at 4.3 billion USD, and L (antineoplastic and immunomodulating agents) had the highest increase at 13.4%; in contrast, J (anti-infectives for systemic use) had the lowest increase in annual average PE at -0.2% in 2020 relative to 2011. Among the 17 OECD countries, Korea had the highest and the third-highest expenditures for ATC codes A and J, respectively. CONCLUSION: PE in Korea has continued to increase between 2011 and 2020, indicating the need for macroscopic management of PE. Our results on PE by ATC code may help health authorities in establishing future policies on PE.

10.
Sci Rep ; 13(1): 7434, 2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-37156854

RESUMO

Heat networks play a vital role in the energy sector by offering thermal energy to residents in certain countries. Effective management and optimization of heat networks require a deep understanding of users' heat usage patterns. Irregular patterns, such as peak usage periods, can exceed the design capacities of the system. However, previous work has mostly neglected the analysis of heat usage profiles or performed on a small scale. To close the gap, this study proposes a data-driven approach to analyze and predict heat load in a district heating network. The study uses data from over eight heating seasons of a cogeneration DH plant in Cheongju, Korea, to build analysis and forecast models using supervised machine learning (ML) algorithms, including support vector regression (SVR), boosting algorithms, and multilayer perceptron (MLP). The models take weather data, holiday information, and historical hourly heat load as input variables. The performance of these algorithms is compared using different training sample sizes of the dataset. The results show that boosting algorithms, particularly XGBoost, are more suitable ML algorithms with lower prediction errors than SVR and MLP. Finally, different explainable artificial intelligence approaches are applied to provide an in-depth interpretation of the trained model and the importance of input variables.

11.
Methods Mol Biol ; 2603: 235-243, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36370284

RESUMO

Secreted proteins play pivotal roles in signal transduction and cell-to-cell communication. Despite increasing interest in secretome analysis over the past decade, most studies on this topic have utilized serum-free medium (SFM). However, fetal bovine serum (FBS) is the most widely used serum supplement for cell culture, and secretome analysis using serum-containing medium (SCM) is important to identify proteins secreted under realistic conditions and to understand their physiological roles. In this chapter, we describe a simple and robust protocol based on bioorthogonal non-canonical amino acid tagging (BONCAT) and pulsed stable isotope labeling by amino acids in cell culture (pSILAC), for identification and quantitation of the cell secretome in SCM. In this protocol, the secretome of SFM is compared with that of SCM to confirm the effect of FBS. Additionally, for mass spectrometric data processing, we provide parameters that increase true positives and decrease both false positives and false negatives.


Assuntos
Aminoácidos , Proteínas , Proteínas/química , Espectrometria de Massas , Técnicas de Cultura de Células , Comunicação Celular , Marcação por Isótopo/métodos
12.
Animals (Basel) ; 12(24)2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36552475

RESUMO

The purpose of this study was to investigate annual changes in BoRVA strains by examining the VP4 and VP7 genes of rotaviruses in Korean calves. Between 2014 and 2018, 35 out of 138 samples of calf diarrhea feces collected nationwide were positive for BoRVA. Further genetic characterization of the VP7 and VP4 genes of 35 BoRVA isolates identified three different G-genotypes (G6, G8, and G10) and two different P genotypes (P[5] and P[11]). The G6 genotype was most common (94.3%) in BoRVA-positive calves, followed by the P[5] genotype (82.9%). Four genotypes comprised combinations of VP4 and VP7: 80% were G6P[5], 14.2% were G6P[11], 2.9% were G8P[5], and 2.9% were G10P[11]. Susceptibility to infection was highest in calves aged < 10 days (35%) and lowest in calves aged 30−50 days (15.4%). The data presented herein suggest that the G6P[5] genotype is the main causative agent of diarrhea in Korean calves. In addition, it is predicted that G6P[5] will continue to act as a major cause of diarrhea in Korean calves.

13.
Int J Mol Sci ; 23(22)2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36430395

RESUMO

Some of the recent studies on drug sensitivity prediction have applied graph neural networks to leverage prior knowledge on the drug structure or gene network, and other studies have focused on the interpretability of the model to delineate the mechanism governing the drug response. However, it is crucial to make a prediction model that is both knowledge-guided and interpretable, so that the prediction accuracy is improved and practical use of the model can be enhanced. We propose an interpretable model called DRPreter (drug response predictor and interpreter) that predicts the anticancer drug response. DRPreter learns cell line and drug information with graph neural networks; the cell-line graph is further divided into multiple subgraphs with domain knowledge on biological pathways. A type-aware transformer in DRPreter helps detect relationships between pathways and a drug, highlighting important pathways that are involved in the drug response. Extensive experiments on the GDSC (Genomics of Drug Sensitivity and Cancer) dataset demonstrate that the proposed method outperforms state-of-the-art graph-based models for drug response prediction. In addition, DRPreter detected putative key genes and pathways for specific drug-cell-line pairs with supporting evidence in the literature, implying that our model can help interpret the mechanism of action of the drug.


Assuntos
Antineoplásicos , Fontes de Energia Elétrica , Redes Neurais de Computação , Aprendizagem , Ensaios de Seleção de Medicamentos Antitumorais , Antineoplásicos/farmacologia
14.
Viruses ; 14(11)2022 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-36423131

RESUMO

Porcine group A rotavirus (PoRVA; family, Reovirideae) strains cause acute viral gastroenteritis in piglets (especially suckling and weaned pigs), resulting in significant economic losses. In this study, we analyzed the VP7 and VP4 genes of PoRVA isolated between 2014 and 2018 from domestic pigs in South Korea to investigate the prevalence of predominant circulating genotypes (G and P types). The prevalence of the PoRVA antigen in the diarrheic fecal samples was 14.1% (53/377). Further genetic characterization of the VP7 and VP4 genes of 53 PoRVA isolates identified six different G-genotypes and five different P genotypes. The G4 and G9 genotypes were the most common (each 39.6%) in PoRVA-positive pigs, followed by P[7] and P[6] (33.9% and 30.1%, respectively). Because the G5 and G9 genotype vaccines are currently mainly used in South Korea, this result provides valuable epidemiological information about the genetic characteristics of PoRVA circulating on domestic pig farms. Development of a novel PoRVA vaccine that targets the current strains circulating in South Korea may be required for more effective virus control on pig farms.


Assuntos
Gastroenterite , Infecções por Rotavirus , Rotavirus , Doenças dos Suínos , Suínos , Animais , Rotavirus/genética , Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/veterinária , Doenças dos Suínos/epidemiologia , Variação Genética , Filogenia
15.
Viruses ; 14(11)2022 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-36366474

RESUMO

Bovine coronavirus (BCoV) causes severe diarrhea in neonatal calves, winter dysentery in adult cattle, and respiratory disease in feedlot cattle, resulting in economic losses. A total of 16/140 calf diarrheic feces samples collected in South Korea between 2017 and 2018 were positive for BCoV. Phylogenetic analysis of the complete spike and hemagglutinin/esterase genes revealed that the 16 Korean BCoV strains belonged to group GIIa along with Korean strains isolated after 2000, whereas Korean BCoV strains isolated before 2000 belonged to group GI. Mice and goats inoculated with an inactivated KBR-1 strain (isolated from this study) generated higher antibody titers (96 ± 13.49 and 73 ± 13.49, respectively) when mixed with the Montanide01 adjuvant than when mixed with the Carbopol or IMS1313 adjuvants. Viral antigens were detected in the large intestine, jejunum, and ileum of calves inoculated with inactivated KBR-1 vaccine (104.0 TCID50/mL) at 14 days of post-challenge (DPC). However, no viral antigens were detected in calves vaccinated with a higher dose of inactivated KBR-1 strain (106.0 TCID50/mL) at 14 DPC, and they had high antibody titers and stable diarrhea scores. Currently, the group GIIa is prevalent in cows in South Korea, and although further research is needed in the future, the recently isolated KBR-1 strain has potential value as a new vaccine candidate.


Assuntos
Doenças dos Bovinos , Infecções por Coronavirus , Coronavirus Bovino , Feminino , Bovinos , Animais , Camundongos , Filogenia , Fezes , Diarreia/veterinária , Antígenos Virais , República da Coreia
16.
Animals (Basel) ; 12(19)2022 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-36230411

RESUMO

Classical swine fever virus (CSFV) is one of the major pathogens that causes severe economic damage to the swine industry. Circulation of CSFV in wild boars carries the potential risk of reintroducing the virus into CSFV-free pig farms. This study carried out a genetic analysis of CSFV isolates from wild boars and analyzed the mtDNA haplotypes of the wild boars. Blood samples (n = 2140) from wild Korean boars captured in 2020 were subjected to qRT-PCR to detect CSFV, which was classified as subgenotype 2.1d based on phylogenetic analysis. CSFV had been detected in wild boars only in northern regions (Gangwon and Gyeonggi) of South Korea between 2011 and 2019. However, CSFV was identified in wild boars in the more southern regions (Chungbuk and Gyeongbuk) in 2020. Based on mitochondrial DNA analysis, all wild boars with CSFV were haplotype 01 (H01). Thus, we presume that the H01 haplotype is more susceptible to CSFV. In the future, infection of wild boars by CSFV is expected to occur intermittently every year, and we predict that most wild boars infected with CSFV will be haplotype H01.

17.
Int J Mol Sci ; 23(19)2022 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-36232792

RESUMO

Molecular and sequencing technologies have been successfully used in decoding biological mechanisms of various diseases. As revealed by many novel discoveries, the role of non-coding RNAs (ncRNAs) in understanding disease mechanisms is becoming increasingly important. Since ncRNAs primarily act as regulators of transcription, associating ncRNAs with diseases involves multiple inference steps. Leveraging the fast-accumulating high-throughput screening results, a number of computational models predicting ncRNA-disease associations have been developed. These tools suggest novel disease-related biomarkers or therapeutic targetable ncRNAs, contributing to the realization of precision medicine. In this survey, we first introduce the biological roles of different ncRNAs and summarize the databases containing ncRNA-disease associations. Then, we suggest a new trend in recent computational prediction of ncRNA-disease association, which is the mode of action (MoA) network perspective. This perspective includes integrating ncRNAs with mRNA, pathway and phenotype information. In the next section, we describe computational methodologies widely used in this research domain. Existing computational studies are then summarized in terms of their coverage of the MoA network. Lastly, we discuss the potential applications and future roles of the MoA network in terms of integrating biological mechanisms for ncRNA-disease associations.


Assuntos
Biologia Computacional , RNA não Traduzido , Biomarcadores , Biologia Computacional/métodos , RNA Mensageiro , RNA não Traduzido/genética , RNA não Traduzido/metabolismo
18.
Viruses ; 14(7)2022 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-35891395

RESUMO

Human Norwalk viruses (HuNoVs), the most common etiological agents of acute gastroenteritis, are genetically diverse RNA viruses that frequently cause mass food poisoning internationally. Although nucleic acid detection methods, such as reverse transcription-quantitative polymerase chain reaction (RT-qPCR), are the gold standard for the diagnosis of norovirus infection, alternative methods are needed for the specific and sensitive viral protein detection for rapid diagnosis and surveillance. In this study, we developed a robust and high-throughput targeted proteomic assay workflow to directly detect the VP1 major capsid protein of HuNoVs. A parallel reaction monitoring (PRM) assay using a high-resolution mass spectrometer was used to detect representative peptides derived from VP1 in six different HuNoV genotypes. An optimized protocol using synthesized heavy isotope-labeled peptides as internal standards was also used to simultaneously genotype and quantify the VP1 protein in human stool specimens. This method is expected to become a new tool for studying the molecular epidemiology of HuNoV and to shed new light on targeted proteomics in clinical practice.


Assuntos
Infecções por Caliciviridae , Norovirus , Proteínas do Capsídeo/genética , Humanos , Espectrometria de Massas , Norovirus/genética , Proteômica
19.
Sci Adv ; 8(13): eabl9156, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35363520

RESUMO

Recent studies using single-cell RNA-sequencing have revealed cellular heterogeneity in the developing mammalian cerebellum, yet the regulatory logic underlying this cellular diversity remains to be elucidated. Using integrated single-cell RNA and ATAC analyses, we resolved developmental trajectories of cerebellar progenitors and identified putative trans- and cis-elements that control cell state transition. We reverse engineered gene regulatory networks (GRNs) of each cerebellar cell type. Through in silico simulations and in vivo experiments, we validated the efficacy of GRN analyses and uncovered the molecular control of a posterior transitory zone (PTZ), a distinct progenitor zone residing immediately anterior to the morphologically defined rhombic lip (RL). We showed that perturbing cell fate specification in the PTZ and RL causes posterior cerebellar vermis hypoplasia, the most common cerebellar birth defect in humans. Our study provides a foundation for comprehensive studies of developmental programs of the mammalian cerebellum.


Assuntos
Malformações do Sistema Nervoso , Transcriptoma , Animais , Diferenciação Celular/genética , Cerebelo/metabolismo , Epigênese Genética , Mamíferos/genética , Camundongos , Malformações do Sistema Nervoso/genética , Malformações do Sistema Nervoso/metabolismo
20.
Vet Sci ; 9(3)2022 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-35324874

RESUMO

On Jeju Island, South Korea, pigs have not been vaccinated against classical swine fever (CSF) since 1999. Analysis of bovine viral diarrhea virus (BVDV) isolated from pigs on Jeju Island between 2009 and 2019 identified five BVDV-1a strains and one BVDV-1b strain. These BVDV types were shown to be the same types as BVDV strains isolated from neighboring cow farms. BVDV antibody-positive pigs (both BVDV-1 and -2) were also detected at 54 of 168 pig farms during this period. In pig infection experiments using BVDV-1a and -2a strains isolated from neighboring cow farms, BVDV-1a was detected in the blood of one of four pigs infected at both 6 and 35 days post-infection (dpi) and in the blood of two of the four pigs at 28 dpi. Pigs showed higher anti-BVDV-1 titers (5.5 ± 1.5 log2) at 35 dpi. BVDV-2a was detected in the blood of one of four pigs infected with this virus at 28 dpi only, and lower antibody titers (2.75 ± 0.75 log2) were seen in these pigs at 35 dpi. While BVDV infection is not particularly pathogenic in pigs, it is still important to monitor porcine BVDV infections due to a differential diagnosis of CSFV.

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