RESUMO
This study aimed to evaluate the differences in the baseline characteristics and patterns of antibiotic usage among hospitals based on their participation in the Korea National Antimicrobial Use Analysis System (KONAS). We obtained claims data from the National Health Insurance for inpatients admitted to all secondary- and tertiary-care hospitals between January 2020 and December 2021 in Korea. 15.9% (58/395) of hospitals were KONAS participants, among which the proportion of hospitals with > 900 beds (31.0% vs. 2.6%, P < 0.001) and tertiary care (50.0% vs. 5.2%, P < 0.001) was higher than that among non-participants. The consumption of antibiotics targeting antimicrobial-resistant gram positive bacteria (33.7 vs. 27.1 days of therapy [DOT]/1,000 patient-days, P = 0.019) and antibiotics predominantly used for resistant gram-negative bacteria (4.8 vs. 3.7 DOT/1,000 patient-days, P = 0.034) was higher in KONAS-participating versus -non-participating hospitals. The current KONAS data do not fully represent all secondary- and tertiary-care hospitals in Korea; thus, the KONAS results should be interpreted with caution.
Assuntos
Antibacterianos , República da Coreia , Humanos , Antibacterianos/uso terapêutico , Hospitais , Centros de Atenção Terciária , Padrões de Prática Médica/estatística & dados numéricos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/isolamento & purificação , Prescrições de Medicamentos/estatística & dados numéricos , Feminino , Masculino , Farmacorresistência BacterianaRESUMO
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/farmacologiaRESUMO
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/metabolismoRESUMO
Between 2016 and 2018, the prevalence of porcine kobuvirus (PKoV) and porcine astrovirus (PAstV) in Korean wild boars (n = 845) was 28.0% and 10.7%, respectively. Coinfection by both viruses was detected in 5.1% of boars. Phylogenetic analysis revealed that 134 PKoV isolates belonged to diverse lineages within the species Aichivirus C; however, one strain (WKoV16CN-8627) clustered with bovine kobuvirus (Aichivirus B). Forty-seven PAstVs belonged to lineage PAstV4, and only one strain (WAst17JN-10931) was a novel addition to lineage PAstV2. The two viruses were more prevalent in boars weighing ≤ 60 kg than in boars weighing > 61 kg.
Assuntos
Kobuvirus/classificação , Kobuvirus/isolamento & purificação , Mamastrovirus/classificação , Mamastrovirus/isolamento & purificação , Filogenia , Sus scrofa/virologia , Animais , Infecções por Astroviridae/epidemiologia , Infecções por Astroviridae/virologia , Bovinos , DNA Viral , Diarreia/virologia , Fezes/virologia , Genótipo , Kobuvirus/genética , Mamastrovirus/genética , Prevalência , República da Coreia/epidemiologia , Análise de Sequência de DNA , Suínos , Doenças dos Suínos/epidemiologia , Doenças dos Suínos/virologiaRESUMO
Porcine parvovirus 1 (PPV1) is a major cause of reproductive failure in pigs. To date, six additional porcine parvoviruses (PPV2-PPV7) have been identified. In this study, we detected 11 PPV1 strains, five PPV3 strains, three PPV4 strains, six PPV5 strains, five PPV6 strains, and one PPV7 strain in Korean wild boars. PPV1, -3, and -5, and PPV6 from Korean wild boars harbor conserved motifs within the Ca2+ binding loop and the catalytic center of the PLA1 motif. Intra-species recombination among PPV7 strains was also identified. Genetic characterization revealed that PPV1 from Korean wild boars may be similar to virulent PPV strains.
Assuntos
DNA Viral/genética , Infecções por Parvoviridae/virologia , Parvovirus Suíno/classificação , Sus scrofa/virologia , Substituição de Aminoácidos , Animais , Feminino , Técnicas de Genotipagem , Masculino , Parvovirus Suíno/genética , Parvovirus Suíno/isolamento & purificação , Filogenia , República da Coreia , SuínosRESUMO
We propose to use cRFP (common Repository of FBS Proteins) in the MS (mass spectrometry) raw data search of cell secretomes. cRFP is a small supplementary sequence list of highly abundant fetal bovine serum proteins added to the reference database in use. The aim behind using cRFP is to prevent the contaminant FBS proteins from being misidentified as other proteins in the reference database, just as we would use cRAP (common Repository of Adventitious Proteins) to prevent contaminant proteins present either by accident or through unavoidable contacts from being misidentified as other proteins. We expect it to be widely used in experiments where the proteins are obtained from serum-free media after thorough washing of the cells, or from a complex media such as SILAC, or from extracellular vesicles directly.
Assuntos
Células Cultivadas/metabolismo , Proteoma/análise , Proteômica/métodos , Soro/química , Animais , Bovinos , Meios de Cultura/química , Bases de Dados de Proteínas , Humanos , Espectrometria de MassasRESUMO
Schwann cells (SCs), the primary glia in the peripheral nervous system (PNS), display remarkable plasticity in that fully mature SCs undergo dedifferentiation and convert to repair SCs upon nerve injury. Dedifferentiated SCs provide essential support for PNS regeneration by producing signals that enhance the survival and axon regrowth of damaged neurons, but the identities of neurotrophic factors remain incompletely understood. Here we show that SCs express and secrete progranulin (PGRN), depending on the differentiation status of SCs. PGRN expression and secretion markedly increased as primary SCs underwent dedifferentiation, while PGRN secretion was prevented by administration of cAMP, which induced SC differentiation. We also found that sciatic nerve injury, a physiological trigger of SC dedifferentiation, induced PGRN expression in SCs in vivo. These results suggest that dedifferentiated SCs express and secrete PGRN that functions as a paracrine factor to support the survival and axon growth of neighboring neurons after injury.
Assuntos
Axônios/patologia , Proliferação de Células/efeitos dos fármacos , Neurônios Motores/patologia , Progranulinas/metabolismo , Células de Schwann/metabolismo , Neuropatia Ciática/patologia , Animais , Axônios/efeitos dos fármacos , Bucladesina/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Técnicas de Cocultura , Meios de Cultivo Condicionados/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Fluoresceínas/metabolismo , Espectrometria de Massas , Camundongos , Camundongos Endogâmicos ICR , Neurônios Motores/efeitos dos fármacos , Progranulinas/farmacologia , RNA Mensageiro/metabolismo , Células de Schwann/química , Medula Espinal/citologiaRESUMO
A maximum clade credibility tree constructed using the full-length spike (S) and hemagglutinin-esterase genes revealed that Vietnamese Bovine coronavirus (BCoV) strains belong to a single cluster (C1); therefore, they might share a common origin with Cuban and Chinese BCoV strains. The omega values of cluster 1 (C1) and cluster 2 (C2) were 0.15734 and 0.11613, respectively, and naive empirical bayes analysis identified two amino acid positions (179 and 501) in the S protein in C1 and three amino acid positions (113, 501, and 525) in that of C2 that underwent positive selection (p > 99%). The evolutionary rate of C1 was estimated to be 7.6206 × 10-4 substitutions/site/year, and the most recent common ancestor (tMRCA) of Vietnamese BCoVs was estimated to date back to 1962 (95% HPD 1950-1973). The effective population sizes of C1 and C2 underwent a rapid reduction after 2000 and 2004, respectively.
Assuntos
Doenças dos Bovinos/genética , Infecções por Coronavirus/virologia , Coronavirus Bovino/genética , Evolução Molecular , Animais , Bovinos , Doenças dos Bovinos/transmissão , Doenças dos Bovinos/virologia , Infecções por Coronavirus/genética , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/veterinária , Coronavirus Bovino/patogenicidade , Fezes/virologia , Glicoproteína da Espícula de Coronavírus/genética , Vietnã , Proteínas do Envelope Viral/genéticaRESUMO
While lipid extraction from wet microalgae has attracted attention as an economical method for microalgal biofuel production, few studies have focused the actual separation of extract phase from the emulsified extraction mixture. Here, a novel approach which utilizes hydrophobic/oleophilic filter was developed for the efficient solvent recovery. The filter was surface-modified by coating a functional polymer via initiated vapor deposition for the selective solvent permeability. While acid-treated Chlorella sorokiniana HS1 and n-hexane was stirred for lipid extraction, tubular filter module was immersed into the mixture for separation. The mixture was kept stirred during the separation to inhibit the buildup of cell debris on the filter by inducing crossflow on the filter. Extract phase was separated directly from the raffinate phase with high separation efficiency (> 98.3%) while maintaining permeation flux. The place-, space- and energy-efficient strategy reported here could be a useful tool for the solvent extraction process.
Assuntos
Chlorella/química , Filtração/instrumentação , Lipídeos/isolamento & purificação , Extração Líquido-Líquido , Microalgas/química , Interações Hidrofóbicas e Hidrofílicas , Lipídeos/química , Solventes/químicaRESUMO
In spite of the huge research interest, ionic polymers could not have been synthesized in the vapor phase because the monomers of ionic polymers contain nonvolatile ionic salts, preventing the monomers from vaporization. Here, we suggest a new, one-step synthetic pathway to form a series of cross-linked ionic polymers (CIPs) in the vapor phase via initiated chemical vapor deposition (iCVD). 2-(Dimethylamino)ethyl methacrylate (DMAEMA) and 4-vinylbenzyl chloride (VBC) monomers are introduced into the iCVD reactor in the vapor phase to form a copolymer film. Simultaneously in the course of the deposition process, the tertiary amine in DMAEMA and benzylic chloride in VBC undergo a Menshutkin nucleophilic substitution reaction to form an ionic ammonium-chloride complex, forming a highly cross-linked ionic copolymer film of p(DMAEMA-co-VBC). To the best of our knowledge, this is the first report on the synthesis of CIP films in the vapor phase. The newly developed CIP thin film is further applied to the surface modification of the membrane for oil/water separation. With the hydrophilic and underwater oleophobic membrane whose surface is modified with the CIP film, excellent separation efficiency (>99%) and unprecedentedly high permeation flux (average 2.32 × 105 L m-2 h-1) are achieved.
RESUMO
Cancer cell secretomes are considered a potential source for the discovery of cancer markers. In this study, the secretomes of four breast cancer (BC) cell lines (Hs578T, MCF-7, MDA-MB-231, and SK-BR-3) were profiled with liquid chromatography-tandem mass spectrometry analysis. A total of 1410 proteins were identified with less than 1% false discovery rate, of which approximately 55% (796 proteins) were predicted to be secreted from cells. To find BC-specific proteins among the secreted proteins, data of immunohistochemical staining compiled in the Human Protein Atlas were investigated by comparing the data of BC tissues with those of normal tissues. By applying various criteria, including higher expression level in BC tissues, higher predicted potential of secretion, and sufficient number of tandem mass spectra, 12 biomarker candidate proteins including ganglioside GM2 activator (GM2A) were selected for confirmation. Western blot analysis and ELISA for plasma samples of healthy controls and BC patients revealed elevation of GM2A in BC patients, especially those who were estrogen receptor-negative. Additionally, siRNA-mediated knockdown of GM2A in BC cells decreased migration in vitro, whereas the overexpression of GM2A led to an increase in cell migration. Although GM2A as a diagnostic and prognostic marker in BC should be carefully verified further, this study has established the potential role of GM2A in BC progression.
Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Movimento Celular , Proteína Ativadora de G(M2)/metabolismo , Proteoma/metabolismo , Proteômica , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/metabolismo , Western Blotting , Neoplasias da Mama/sangue , Estudos de Casos e Controles , Linhagem Celular Tumoral , Movimento Celular/genética , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Proteína Ativadora de G(M2)/deficiência , Humanos , Proteínas de Neoplasias/análise , Proteínas de Neoplasias/sangue , Proteínas de Neoplasias/metabolismo , Estadiamento de Neoplasias , Proteoma/análiseRESUMO
Sirtuins are NAD(+) -dependent deacetylases that regulate a range of cellular processes. Although diverse functions of sirtuins have been proposed, those functions of SIRT6 and SIRT7 that are mediated by their interacting proteins remain elusive. In the present study, we identified SIRT6- and SIRT7-interacting proteins, and compared their interactomes to investigate functional links. Our interactomes revealed 136 interacting proteins for SIRT6 and 233 for SIRT7 while confirming seven and 111 proteins identified previously for SIRT6 and SIRT7, respectively. Comparison of SIRT6 and SIRT7 interactomes under the same experimental conditions disclosed 111 shared proteins, implying related functional links. The interaction networks of interactomes indicated biological processes associated with DNA repair, chromatin assembly, and aging. Interactions of two highly acetylated proteins, nucleophosmin (NPM1) and nucleolin, with SIRT6 and SIRT7 were confirmed by co-immunoprecipitation. NPM1 was found to be deacetylated by both SIRT6 and SIRT7. In senescent cells, the acetylation level of NPM1 was increased in conjunction with decreased levels of SIRT6 and SIRT7, suggesting that the acetylation of NPM1 could be regulated by SIRT6 and SIRT7 in the aging process. Our comparative interactomic study of SIRT6 and SIRT7 implies important functional links to aging by their associations with interacting proteins. All MS data have been deposited in the ProteomeXchange with identifiers PXD000159 and PXD000850 (http://proteomecentral.proteomexchange.org/dataset/PXD000159, http://proteomecentral.proteomexchange.org/dataset/PXD000850).
Assuntos
Mapas de Interação de Proteínas , Sirtuínas/metabolismo , Acetilação , Envelhecimento , Células HEK293 , Humanos , Imunoprecipitação , Proteínas Nucleares/análise , Proteínas Nucleares/metabolismo , Nucleofosmina , Fosfoproteínas/análise , Fosfoproteínas/metabolismo , Proteômica/métodos , Proteínas de Ligação a RNA/análise , Proteínas de Ligação a RNA/metabolismo , Sirtuínas/análise , Espectrometria de Massas em Tandem/métodos , NucleolinaRESUMO
To discover serological colorectal cancer (CRC) markers, we analyzed cell line secretome to gather proteins of higher potential to be secreted from tissues into circulation. A total of 898 human proteins were identified, of which 62.2% were predicted to be released or shed from cells. The identified proteins were compared with tissue proteomes to find candidate proteins whose expressions were elevated in tumor tissues compared with normal tissues as revealed by (i) quantitative proteomic analysis based on cICAT and mTRAQ or (ii) data mining of immunohistochemical images piled in Human Protein Atlas database. By applying various stringent criteria, 11 candidate proteins were selected. Among these, we validated an significant increase (p = 0.0018) of melanotransferrin (TRFM) at the plasma level of CRC patients through Western blotting, using 130 plasma samples containing 30 healthy controls, 80 CRC patients, and 20 patients of other diseases. Finally, we measured the expression level of TRFM in 325 plasma samples containing 77 healthy controls and 228 CRC patients (34.6 ± 4.2 ng/mL and 67.0 ± 6.4 ng/mL, p < 0.0001) through ELISA and demonstrated the area under the receiver operating characteristic curve of 0.723 (p < 0.0001) with a 92.5% specificity, 48.2% sensitivity, and 95.7% positive predictive value. Furthermore, unlike CEA and PAI-1, up-regulation of TRFM in pathological stages I & II groups compared with stages III & IV groups lead us to expect the use TRFM for early-stage diagnosis of CRC. In this study, we suggest TRFM as a potential serological marker for CRC and expect our discovery strategy to help identify highly cancer-specific and body-fluid-accessible biomarkers.
Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Colorretais/diagnóstico , Regulação Neoplásica da Expressão Gênica/fisiologia , Glicoproteínas de Membrana/sangue , Proteômica/métodos , Área Sob a Curva , Western Blotting , Cromatografia Líquida , Neoplasias Colorretais/sangue , Biologia Computacional , Mineração de Dados , Ensaio de Imunoadsorção Enzimática , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Imuno-Histoquímica , Glicoproteínas de Membrana/genética , Espectrometria de Massas em TandemRESUMO
Solid-pseudopapillary neoplasm is an uncommon pancreatic tumor with distinct clinicopathologic features. Solid-pseudopapillary neoplasms are characterized by mutations in exon 3 of CTNNB1. However, little is known about the gene and microRNA expression profiles of solid-pseudopapillary neoplasms. Thus, we sought to characterize solid-pseudopapillary neoplasm-specific gene expression and identify the signaling pathways activated in these tumors. Comparisons of gene expression in solid-pseudopapillary neoplasm to pancreatic ductal carcinomas, neuroendocrine tumors, and non-neoplastic pancreatic tissues identified solid-pseudopapillary neoplasm-specific mRNA and microRNA profiles. By analyzing 1686 (1119 upregulated and 567 downregulated) genes differentially expressed in solid-pseudopapillary neoplasm, we found that the Wnt/ß-catenin, Hedgehog, and androgen receptor signaling pathways, as well as genes involved in epithelial mesenchymal transition, are activated in solid-pseudopapillary neoplasms. We validated these results experimentally by assessing the expression of ß-catenin, WIF-1, GLI2, androgen receptor, and epithelial-mesenchymal transition-related markers with western blotting and immunohistochemistry. Our analysis also revealed 17 microRNAs, especially the miR-200 family and miR-192/215, closely associated with the upregulated genes associated with the three pathways activated in solid-pseudopapillary neoplasm and epithelial mesenchymal transition. Our results provide insight into the molecular mechanisms underlying solid-pseudopapillary neoplasm tumorigenesis and its characteristic less epithelial cell differentiation than the other common pancreatic tumors.
Assuntos
Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pancreáticas/genética , Transdução de Sinais/genética , Biomarcadores Tumorais/análise , Transformação Celular Neoplásica/genética , Análise por Conglomerados , Transição Epitelial-Mesenquimal/genética , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Proteínas Hedgehog/genética , Humanos , MicroRNAs/análise , Neoplasias Pancreáticas/química , Neoplasias Pancreáticas/patologia , RNA Mensageiro/análise , Receptores Androgênicos/genética , Reprodutibilidade dos Testes , Estudos Retrospectivos , Via de Sinalização Wnt/genéticaRESUMO
This essay examines the period between 1897 and 1910, when trachoma, a contagious eye disease, became an "Oriental" problem that justified exclusionary immigration policy against Asians entering the United States. It also investigates the ways in which the public fear and alleged threat of the eye disease destabilized and undermined the rights of Asian immigrants. Many scholars have explored the link between trachoma and southern and eastern European newcomers, in particular Jews, but they have not paid much attention to Chinese or Japanese immigrants, for whose exclusion trachoma played a significant role. This is primarily because the number of Asian immigrants was much smaller than that of their European counterparts and because the Chinese Exclusion Acts, which had already been in place, functioned as a stronger and more lasting deterrent to Asian immigration than exclusion or deportation through medical inspection. Moreover, into the 1910s, medical and scientific innovations for detecting parasitic diseases (e.g. hookworm) helped American authorities exclude Asians in larger numbers. Still, the analysis of the discourses surrounding trachoma and immigration from Asia, though short-lived, demonstrates the role of medical inspection in controlling and regulating Asian immigrants, in particular Chinese and Japanese, into the United States and in constructing their legal and political rights. In 1906, the fear of trachoma justified an order to segregate Japanese students from white children in San Francisco even at the cost of compromising their rights as citizens. Along with fierce criticisms against immigration officials by the American public, the 1910 investigation of the San Francisco Immigration Office problematized the admission of trachoma-afflicted Asian immigrants. Those critical of the Immigration Office and its implementation of American immigration policy called for exclusionary measures to limit the privileges of exempt classes and domiciled aliens and hinder the exertion of their rights to leave and reenter their adopted country. The two examples show that trachoma was a convenient excuse to condemn inefficient immigration policy and regulate allegedly diseased Asian bodies. In 1910, the federal government made a decision to relegate to steamship companies full responsibility for medical inspection at Asian ports. Since they had to pay a fine for every immigrant excluded at American borders for medical reasons, including trachoma, steamship companies carried out more rigorous examinations. With medical advancements and growing interest in parasitic diseases, trachoma soon lost its appeal to immigration authorities. However, the association of immigration, race, and disease has continued to provide a rationale for immigration control beyond American borders.
Assuntos
Emigrantes e Imigrantes/história , Emigração e Imigração/história , Tracoma/história , Emigrantes e Imigrantes/legislação & jurisprudência , Emigração e Imigração/legislação & jurisprudência , Ásia Oriental/etnologia , História do Século XIX , História do Século XX , Humanos , Tracoma/etnologia , Tracoma/prevenção & controle , Estados UnidosRESUMO
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 RetrospectivosRESUMO
Aim: To determine the trends in the usage of antimicrobial drugs by patients with pneumonia with prescriptions from long-term care (LTC) hospitals in the Republic of Korea. Method: This retrospective study was conducted from 2011 to 2022 using the National Health Insurance Review and Assessment Service claim data in Korea. We calculated antibiotic usage expressed as a daily defined dose (DDD) per 1000 patients per day (DID). Results: The number of patients with pneumonia in LTC hospitals increased by 2.7 times, from 30,000 in 2011 to 79,000 in 2022. Furthermore, antibiotic consumption per episode by patients with pneumonia in LTC hospitals increased from 17.14 DDD in 2011 to 18.11 DDD in 2022. Among the Access, Watch, and Reserve classification groups, the Watch group showed the highest usage; further, the Access group showed a decreasing trend, whereas the Watch and Reserve groups showed an increasing trend (p < 0.01). In the Watch group, the most commonly used antibiotic was J01CR05 (piperacillin and beta-lactamase inhibitor), followed in order by J01DD04 (ceftriaxone), J01MA12 (levofloxacin), and J01DH02 (meropenem). In the Reserve group, J01XB01 (colistin) and J01AA12 (tigecycline) were commonly used. Conclusion: The antibiotics prescribed for pneumonia in LTC hospitals have continuously increased the use of broad-spectrum antibiotics. Accordingly, appropriate use of antibiotics in LTC hospital settings and assessment of antibiotics used are warranted.
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.
RESUMO
Neuromodulation technologies are crucial for investigating neuronal connectivity and brain function. Magnetic neuromodulation offers wireless and remote deep brain stimulations that are lacking in optogenetic- and wired-electrode-based tools. However, due to the limited understanding of working principles and poorly designed magnetic operating systems, earlier magnetic approaches have yet to be utilized. Furthermore, despite its importance in neuroscience research, cell-type-specific magnetic neuromodulation has remained elusive. Here we present a nanomaterials-based magnetogenetic toolbox, in conjunction with Cre-loxP technology, to selectively activate genetically encoded Piezo1 ion channels in targeted neuronal populations via torque generated by the nanomagnetic actuators in vitro and in vivo. We demonstrate this cell-type-targeting magnetic approach for remote and spatiotemporal precise control of deep brain neural activity in multiple behavioural models, such as bidirectional feeding control, long-term neuromodulation for weight control in obese mice and wireless modulation of social behaviours in multiple mice in the same physical space. Our study demonstrates the potential of cell-type-specific magnetogenetics as an effective and reliable research tool for life sciences, especially in wireless, long-term and freely behaving animals.
RESUMO
Lung cancer-related transcription factors (TFs) were identified by integrating previously reported genomic, transcriptomic, and proteomic data and were quantified by multiple reaction monitoring (MRM) in various cell lines. All experiments were performed without affinity depletion or subfractionation of cell lysates. Since the target proteins were expected to be present in low abundance, we experimentally optimized MRM transition parameters with chemically synthesized peptides. Quantitation was based on stable isotope-labeled standard peptides (SIS peptides). Out of 288 MRM measurements (36 peptides representing 28 TFs × 8 cell lines), 241 were successfully obtained within a quantitation limit of 15 amol, 221 measurements (91.7%) showed coefficients of variation (CVs) of ≤ 20%, and 149 (61.8%) showed CVs of ≤ 10%, quantifying as low as 19.4 amol/µg protein for STAT2 with a CV of 6.3% in an A549 cell. Comparisons between MRM measurements and levels of the corresponding mRNAs revealed linear, nonlinear, or no relationship between protein and mRNA levels, indicating the need for an MRM assay. An integrative analysis of MRM and gene expression profiles from doxorubicin-resistant H69AR and sensitive H69 cells further showed that 14 differentially expressed TFs, such as STAT1 and SMAD4, regulated genes associated with drug resistance and cell differentiation-related processes. Thus, the analytical performance of MRM for the quantitation of low abundance TFs suggests its usefulness for biological application.