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1.
Exp Dermatol ; 33(1): e15015, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38284203

RESUMEN

IMP-3 expression is a poor prognostic factor of melanomas and it promotes melanoma cell migration and invasion by a pathway modulating HMGA2 mRNA expression. We tried to identify other putative targets of IMP-3. We identified putative IMP-3-binding RNAs, including AKT1, MAPK3, RB1 and RELA, by RNA immunoprecipitation coupled with next-generation sequencing. IMP-3 overexpression increased AKT and RELA levels in MeWo cells. siRNAs against AKT1 and RELA inhibited MeWo/Full-length IMP-3 cell migration. IMP-3 knockdown of A2058 cells decreased AKT1 and RELA expression and lowered migration ability. Co-transfection of A2058 cells with AKT1- or RELA-expressing plasmids with IMP-3 siRNA restored the inhibitory effects of IMP-3 knockdown on migration. HMGA2 did not influence AKT1 and RELA expression in melanoma cells. Human melanoma samples with high IMP-3 levels also showed high HMGA2, AKT1 and RELA expression. Our results show that IMP-3 enhances melanoma cell migration through the regulation of the AKT1 and RELA axis.


Asunto(s)
Melanoma , Proteínas Proto-Oncogénicas c-akt , Proteínas de Unión al ARN , Factor de Transcripción ReIA , Humanos , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Melanoma/genética , Melanoma/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Interferente Pequeño , Factor de Transcripción ReIA/genética , Factor de Transcripción ReIA/metabolismo , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo
2.
Nucleic Acids Res ; 50(W1): W616-W622, 2022 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-35536289

RESUMEN

With the proliferation of genomic sequence data for biomedical research, the exploration of human genetic information by domain experts requires a comprehensive interrogation of large numbers of scientific publications in PubMed. However, a query in PubMed essentially provides search results sorted only by the date of publication. A search engine for retrieving and interpreting complex relations between biomedical concepts in scientific publications remains lacking. Here, we present pubmedKB, a web server designed to extract and visualize semantic relationships between four biomedical entity types: variants, genes, diseases, and chemicals. pubmedKB uses state-of-the-art natural language processing techniques to extract semantic relations from the large number of PubMed abstracts. Currently, over 2 million semantic relations between biomedical entity pairs are extracted from over 33 million PubMed abstracts in pubmedKB. pubmedKB has a user-friendly interface with an interactive semantic graph, enabling the user to easily query entities and explore entity relations. Supporting sentences with the highlighted snippets allow to easily navigate the publications. Combined with a new explorative approach to literature mining and an interactive interface for researchers, pubmedKB thus enables rapid, intelligent searching of the large biomedical literature to provide useful knowledge and insights. pubmedKB is available at https://www.pubmedkb.cc/.


Asunto(s)
Computadores , Motor de Búsqueda , Humanos , PubMed , Semántica , Minería de Datos/métodos
3.
BMC Med Educ ; 24(1): 154, 2024 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-38374112

RESUMEN

BACKGROUND: To implement the ACGME Anesthesiology Milestone Project in a non-North American context, a process of indigenization is essential. In this study, we aim to explore the differences in perspective toward the anesthesiology competencies among residents and junior and senior visiting staff members and co-produce a preliminary framework for the following nation-wide survey in Taiwan. METHODS: The expert committee translation and Delphi technique were adopted to co-construct an indigenized draft of milestones. Descriptive analysis, chi-square testing, Pearson correlation testing, and repeated-measures analysis of variance in the general linear model were employed to calculate the F values and mean differences (MDs). RESULTS: The translation committee included three experts and the consensus panel recruited 37 participants from four hospitals in Taiwan: 9 residents, 13 junior visiting staff members (JVSs), and 15 senior visiting staff members (SVSs). The consensus on the content of the 285 milestones was achieved after 271 minor and 6 major modifications in 3 rounds of the Delphi survey. Moreover, JVSs were more concerned regarding patient care than were both residents (MD = - 0.095, P < 0.001) and SVSs (MD = 0.075, P < 0.001). Residents were more concerned regarding practice-based learning improvement than were JVSs (MD = 0.081; P < 0.01); they also acknowledged professionalism more than JVSs (MD = 0.072; P < 0.05) and SVSs (MD = 0.12; P < 0.01). Finally, SVSs graded interpersonal and communication skills lower than both residents (MD = 0.068; P < 0.05) and JVSs (MD = 0.065; P < 0.05) did. CONCLUSIONS: Most ACGME anesthesiology milestones are applicable and feasible in Taiwan. Incorporating residents' perspectives may bring insight and facilitate shared understanding to a new educational implementation. This study helped Taiwan generate a well-informed and indigenized draft of a competency-based framework for the following nation-wide Delphi survey.


Asunto(s)
Anestesiología , Internado y Residencia , Humanos , Anestesiología/educación , Taiwán , Técnica Delphi , Competencia Clínica , Educación de Postgrado en Medicina
4.
Am J Pathol ; 192(1): 130-145, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34619135

RESUMEN

High circulating lipids occurring in obese individuals and insulin-resistant patients are considered a contributing factor to type 2 diabetes. Exposure to high lipid concentration is proposed to both protect and damage beta-cells under different circumstances. Here, by feeding mice a high-fat diet (HFD) for 2 weeks to up to 14 months, the study showed that HFD initially causes the beta-cells to expand in population, whereas long-term exposure to HFD is associated with failure of beta-cells and the inability of animals to respond to glucose challenge. To prevent the failure of beta-cells and the development of type 2 diabetes, the molecular mechanisms that underlie this biphasic response of beta-cells to lipid exposure were explored. Using palmitic acid (PA) in cultured beta-cells and islets, the study demonstrated that chronic exposure to lipids leads to reduced viability and inhibition of cell cycle progression concurrent with down-regulation of a pro-growth/survival kinase AKT, independent of glucose. This AKT down-regulation by PA is correlated with the induction of mTOR/S6K activity. Inhibiting mTOR activity with rapamycin induced Raptor and restored AKT activity, allowing beta-cells to gain proliferation capacity that was lost after HFD exposure. In summary, a novel mechanism in which lipid exposure may cause the dipole effects on beta-cell growth was elucidated, where mTOR acts as a lipid sensor. These mechanisms can be novel targets for future therapeutic developments.


Asunto(s)
Regulación hacia Abajo , Células Secretoras de Insulina/enzimología , Ácido Palmítico/toxicidad , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Animales , Apoptosis/efectos de los fármacos , Línea Celular , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Ciclina D2/metabolismo , Dieta Alta en Grasa , Regulación hacia Abajo/efectos de los fármacos , Activación Enzimática/efectos de los fármacos , Células Secretoras de Insulina/efectos de los fármacos , Ratones , Fosfohidrolasa PTEN/metabolismo , Fosforilación/efectos de los fármacos , Proteína Reguladora Asociada a mTOR/metabolismo , Proteínas Quinasas S6 Ribosómicas 70-kDa/metabolismo
5.
Nucleic Acids Res ; 49(D1): D1152-D1159, 2021 01 08.
Artículo en Inglés | MEDLINE | ID: mdl-33035337

RESUMEN

The current state of the COVID-19 pandemic is a global health crisis. To fight the novel coronavirus, one of the best-known ways is to block enzymes essential for virus replication. Currently, we know that the SARS-CoV-2 virus encodes about 29 proteins such as spike protein, 3C-like protease (3CLpro), RNA-dependent RNA polymerase (RdRp), Papain-like protease (PLpro), and nucleocapsid (N) protein. SARS-CoV-2 uses human angiotensin-converting enzyme 2 (ACE2) for viral entry and transmembrane serine protease family member II (TMPRSS2) for spike protein priming. Thus in order to speed up the discovery of potential drugs, we develop DockCoV2, a drug database for SARS-CoV-2. DockCoV2 focuses on predicting the binding affinity of FDA-approved and Taiwan National Health Insurance (NHI) drugs with the seven proteins mentioned above. This database contains a total of 3,109 drugs. DockCoV2 is easy to use and search against, is well cross-linked to external databases, and provides the state-of-the-art prediction results in one site. Users can download their drug-protein docking data of interest and examine additional drug-related information on DockCoV2. Furthermore, DockCoV2 provides experimental information to help users understand which drugs have already been reported to be effective against MERS or SARS-CoV. DockCoV2 is available at https://covirus.cc/drugs/.


Asunto(s)
Antivirales/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Bases de Datos Farmacéuticas/estadística & datos numéricos , SARS-CoV-2/efectos de los fármacos , Antivirales/metabolismo , COVID-19/epidemiología , COVID-19/virología , Curaduría de Datos/métodos , Minería de Datos/métodos , Humanos , Internet , Modelos Moleculares , Pandemias , Unión Proteica/efectos de los fármacos , Dominios Proteicos , SARS-CoV-2/metabolismo , SARS-CoV-2/fisiología , Proteínas Virales/química , Proteínas Virales/metabolismo , Replicación Viral/efectos de los fármacos
6.
Int J Mol Sci ; 24(8)2023 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-37108701

RESUMEN

Compared to other techniques, RNA sequencing (RNA-Seq) has the advantage of having details of the expression abundance of all transcripts in a single run. In this study, we used RNA-Seq to monitor the maturity and dynamic characteristics of in vitro hepatocyte cultures. Hepatocytes, including mature hepatocytes and small hepatocytes, were analyzed in vitro using RNA-Seq and quantitative polymerase chain reaction (qPCR). The results demonstrated that the gene expression profiles measured by RNA-Seq showed a similar trend to the expression profiles measured by qPCR, and can be used to infer the success of in vitro hepatocyte cultures. The results of the differential analysis, which compared mature hepatocytes against small hepatocytes, revealed 836 downregulated and 137 upregulated genes. In addition, the success of the hepatocyte cultures could be explained by the gene list screened from the adopted gene enrichment test. In summary, we demonstrated that RNA-Seq could become an effective method for monitoring the whole transcriptome of hepatocyte cultures and provide a more comprehensive list of factors related to the differentiation of small hepatocytes into mature hepatocytes. This monitoring system not only shows high potential in medical applications but may also be a novel method for the clinical diagnosis of liver-related diseases.


Asunto(s)
Hepatocitos , Transcriptoma , Ratas , Animales , RNA-Seq , Hepatocitos/metabolismo , Análisis de Secuencia de ARN , Células Cultivadas , Hígado
7.
J Neurosci ; 41(13): 2828-2841, 2021 03 31.
Artículo en Inglés | MEDLINE | ID: mdl-33632727

RESUMEN

Common fusion machinery mediates the Ca2+-dependent exocytosis of synaptic vesicles (SVs) and dense-core vesicles (DCVs). Previously, Synapsin Ia (Syn Ia) was found to localize to SVs, essential for mobilizing SVs to the plasma membrane through phosphorylation. However, whether (or how) the phosphoprotein Syn Ia plays a role in regulating DCV exocytosis remains unknown. To answer these questions, we measured the dynamics of DCV exocytosis by using single-vesicle amperometry in PC12 cells (derived from the pheochromocytoma of rats of unknown sex) overexpressing wild-type or phosphodeficient Syn Ia. We found that overexpression of phosphodeficient Syn Ia decreased the DCV secretion rate, specifically via residues previously shown to undergo calmodulin-dependent kinase (CaMK)-mediated phosphorylation (S9, S566, and S603). Moreover, the fusion pore kinetics during DCV exocytosis were found to be differentially regulated by Syn Ia and two phosphodeficient Syn Ia mutants (Syn Ia-S62A and Syn Ia-S9,566,603A). Kinetic analysis suggested that Syn Ia may regulate the closure and dilation of DCV fusion pores via these sites, implying the potential interactions of Syn Ia with certain DCV proteins involved in the regulation of fusion pore dynamics. Furthermore, we predicted the interaction of Syn Ia with several DCV proteins, including Synaptophysin (Syp) and soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) proteins. By immunoprecipitation, we found that Syn Ia interacted with Syp via phosphorylation. Moreover, a proximity ligation assay (PLA) confirmed their phosphorylation-dependent, in situ interaction on DCVs. Together, these findings reveal a phosphorylation-mediated regulation of DCV exocytosis by Syn Ia.SIGNIFICANCE STATEMENT Although they exhibit distinct exocytosis dynamics upon stimulation, synaptic vesicles (SVs) and dense-core vesicles (DCVs) may undergo co-release in neurons and neuroendocrine cells through an undefined molecular mechanism. Synapsin Ia (Syn Ia) is known to recruit SVs to the plasma membrane via phosphorylation. Here, we examined whether Syn Ia also affects the dynamics of DCV exocytosis. We showed that Syn Ia regulates the DCV secretion rate and fusion pore kinetics during DCV exocytosis. Moreover, Syn Ia-mediated regulation of DCV exocytosis depends on phosphorylation. We further found that Syn Ia interacts with Synaptophysin (Syp) on DCVs in a phosphorylation-dependent manner. Thus, these results suggest that Syn Ia may regulate the release of DCVs via phosphorylation.


Asunto(s)
Membrana Celular/metabolismo , Exocitosis/fisiología , Vesículas Secretoras/metabolismo , Sinapsinas/metabolismo , Vesículas Sinápticas/metabolismo , Animales , Células PC12 , Fosfoproteínas/metabolismo , Ratas
8.
Bioinformatics ; 38(1): 30-37, 2021 12 22.
Artículo en Inglés | MEDLINE | ID: mdl-34398217

RESUMEN

MOTIVATION: To facilitate the process of tailor-making a deep neural network for exploring the dynamics of genomic DNA, we have developed a hands-on package called ezGeno. ezGeno automates the search process of various parameters and network structures and can be applied to any kind of 1D genomic data. Combinations of multiple abovementioned 1D features are also applicable. RESULTS: For the task of predicting TF binding using genomic sequences as the input, ezGeno can consistently return the best performing set of parameters and network structure, as well as highlight the important segments within the original sequences. For the task of predicting tissue-specific enhancer activity using both sequence and DNase feature data as the input, ezGeno also regularly outperforms the hand-designed models. Furthermore, we demonstrate that ezGeno is superior in efficiency and accuracy compared to the one-layer DeepBind model and AutoKeras, an open-source AutoML package. AVAILABILITY AND IMPLEMENTATION: The ezGeno package can be freely accessed at https://github.com/ailabstw/ezGeno. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Asunto(s)
Genómica , Programas Informáticos , Genoma , Unión Proteica , Redes Neurales de la Computación
9.
Am J Pathol ; 191(7): 1240-1254, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33894178

RESUMEN

The estrogen-related receptor (ERR) family of orphan nuclear receptors are transcriptional activators for genes involved in mitochondrial bioenergetics and metabolism. The goal of this study was to explore the role of ERRα in lipid metabolism and the potential effect of inhibiting ERRα on the development of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). In the current study, three experimental mouse models: high-fat diet, high-carbohydrate diet, and a genetic model of hepatic insulin resistance where the liver hyperinsulinemia signal is mimicked via hepatic deletion of Pten (phosphatase and tensin homolog deleted on chromosome 10), the negative regulator of the insulin/phosphatidylinositol 3-kinase signaling pathway, were used. A recently developed small-molecule inhibitor for ERRα was used to demonstrate that inhibiting ERRα blocked NAFLD development induced by either high-carbohydrate diet or high-fat diet feeding. ERRα inhibition also diminished lipid accumulation and attenuated NASH development in the Pten null mice. Glycerolipid synthesis was discovered as an additional mechanism for ERRα-regulated NAFLD/NASH development and glycerophosphate acyltransferase 4 was identified as a novel transcriptional target of ERRα. In summary, these results establish ERRα as a major transcriptional regulator of lipid biosynthesis in addition to its characterized primary function as a regulator for mitochondrial function. This study recognizes ERRα as a potential target for NAFLD/NASH treatment and elucidates novel signaling pathways regulated by ERRα.


Asunto(s)
Metabolismo de los Lípidos/fisiología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Receptores de Estrógenos/metabolismo , Triglicéridos/biosíntesis , Animales , Regulación de la Expresión Génica/fisiología , Lipogénesis/fisiología , Masculino , Ratones , Receptor Relacionado con Estrógeno ERRalfa
10.
Opt Express ; 30(23): 42129-42140, 2022 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-36366672

RESUMEN

In this study, a miniaturized full-color holographic reconstruction system that uses a single spatial light modulator to achieve full-color image reconstruction was developed. The reconstruction system uses a single light guide for light combination and is therefore less voluminous than conventional reconstruction systems. The experimental results demonstrated that the system had a full-color display, corrected light combination, and eliminated zero-order light. The vibrations of the light guide disrupted the temporal coherence of the laser beam, thus ensuring that the speckle in the reconstructed image was almost imperceptible to the human eye.

11.
BMC Infect Dis ; 22(1): 848, 2022 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-36376846

RESUMEN

BACKGROUND: Hepatitis C virus (HCV) is a global public health problem, with ~ 11 million people in Africa infected. There is incomplete information on HCV in Sudan, particularly in haemodialysis patients, who have a higher prevalence compared to the general population. Thus, our objectives were to genotype and molecularly characterize HCV isolated from end-stage renal disease haemodialysis patients. METHODS: A total of 541 patients were recruited from eight haemodialysis centres in Khartoum and screened for anti-HCV. Viral loads were determined using in-house real-time PCR in seropositive patients. HCV was genotyped and subtyped using sequencing of amplicons of 5' untranslated (UTR) and non-structural protein 5B (NS5B) regions, followed by phylogenetic analysis of corresponding sequences. RESULTS: The HCV seroprevalence in the study was 17% (93/541), with HCV RNA-positive viremic rate of 7% (40/541). A low HCV load, with a mean of 2.85 × 104 IU/ml and a range of 2.95 × 103 to 4.78 × 106 IU/ml, was detected. Phylogenetic analyses showed the presence of genotypes 1, 3, 4, and 5 with subtypes 1a, 1b, 1 g, 3a, 4a, 4 l, 4 m, 4 s, and 4t. Sequences of HCV from the same haemodialysis units, clustered in similar genotypes and subtypes intimating nosocomial infection. CONCLUSION: HCV infection is highly prevalent in haemodialysis patients from Sudan, with phylogenetic analysis intimating nosocomial infection. HCV genotyping is useful to locate potential transmission chains and to enable individualized treatment using highly effective direct-acting antivirals (DAAs).


Asunto(s)
Infección Hospitalaria , Hepatitis C Crónica , Hepatitis C , Fallo Renal Crónico , Humanos , Hepacivirus/genética , Genotipo , Antivirales , Estudios Seroepidemiológicos , Filogenia , Diálisis Renal , Fallo Renal Crónico/terapia , Infección Hospitalaria/epidemiología , Sudán/epidemiología
12.
Retina ; 42(4): 797-806, 2022 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-34923510

RESUMEN

PURPOSE: To investigate the relationship between different CYP4V2 disease-causing variants and disease severity in Bietti crystalline dystrophy (BCD). METHODS: Twenty-one subjects from 19 unrelated families with a clinical diagnosis of BCD were enrolled. A novel severity prediction score for BCD based on the predicted molecular impact of CYP4V2 variants was applied for grouping and subsequent analyses. The more severe variants led to less CYP4V2 protein function preservation and a higher severity prediction score. RESULTS: All subjects harbored two alleles of CYP4V2 disease-causing variants, of which c.802-8_810del17insGC was the most prevalent (14/21, 66.67%) and c.1507G>C was novel. According to the severity score, the subjects were categorized into severe, moderate, and mild groups with different preservation of central vision (mean logMAR visual acuity 0.95 ± 0.82, 0.89 ± 1.22, and 0.56 ± 0.64, respectively). The patients with a lower severity score had slower disease progression. CONCLUSION: This is the first cohort study of BCD in Taiwan, and we established a novel BCD severity index based on the molecular impact of different CYP4V2 variants. More severe impairment of CYP4V2 protein led to a more severe disease course with earlier progression. Our results could be helpful in identifying a therapeutic window for patients with BCD.


Asunto(s)
Distrofias Hereditarias de la Córnea , Enfermedades de la Retina , Estudios de Cohortes , Distrofias Hereditarias de la Córnea/diagnóstico , Distrofias Hereditarias de la Córnea/genética , Familia 4 del Citocromo P450/genética , Familia 4 del Citocromo P450/metabolismo , Análisis Mutacional de ADN , Humanos , Mutación , Linaje , Enfermedades de la Retina/diagnóstico , Enfermedades de la Retina/genética
13.
Nucleic Acids Res ; 48(3): 1175-1191, 2020 02 20.
Artículo en Inglés | MEDLINE | ID: mdl-31853539

RESUMEN

Precise noncoding RNA (ncRNA)-based network prediction is necessary to reveal ncRNA functions and pathological mechanisms. Here, we established a systemic pipeline to identify prognostic ncRNAs, predict their functions and explore their pathological mechanisms in lung adenocarcinoma (LUAD). After in silico and experimental validation based on evaluations of prognostic value in multiple LUAD cohorts, we selected the PTTG3P pseudogene from among other prognostic ncRNAs (MIR497HG, HSP078, TBX5-AS1, LOC100506990 and C14orf64) for mechanistic studies. PTTG3P upregulation in LUAD cells shortens the metaphase to anaphase transition in mitosis, increases cell viability after cisplatin or paclitaxel treatment, facilitates tumor growth that leads to poor survival in orthotopic lung models, and is associated with a poor survival rate in LUAD patients in the TCGA cohort who received chemotherapy. Mechanistically, PTTG3P acts as an ncRNA that interacts with the transcription factor FOXM1 to regulate the transcriptional activation of the mitotic checkpoint kinase BUB1B, which augments tumor growth and chemoresistance and leads to poor outcomes for LUAD patients. Overall, we established a systematic strategy to uncover prognostic ncRNAs with functional prediction methods suitable for pan-cancer studies. Moreover, we revealed that PTTG3P, due to its upregulation of the PTTG3P/FOXM1/BUB1B axis, could be a therapeutic target for LUAD patients.


Asunto(s)
Adenocarcinoma/genética , Neoplasias Pulmonares/genética , ARN no Traducido/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Animales , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Proliferación Celular , Cromatina/genética , Simulación por Computador , Resistencia a Antineoplásicos/genética , Proteína Forkhead Box M1/metabolismo , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Ratones , Mitosis , Pronóstico , Proteínas Serina-Treonina Quinasas/metabolismo , Transducción de Señal
14.
BMC Pediatr ; 22(1): 168, 2022 03 31.
Artículo en Inglés | MEDLINE | ID: mdl-35361141

RESUMEN

BACKGROUND: Tenofovir disoproxil fumarate (TDF) is effectively used as the first-line antiviral for chronic hepatitis B virus (HBV) infection in adults and children older than 12 years. To date, no confirmed case of virologic breakthrough (VBT) in a pediatric case has been reported. CASE PRESENTATION: Here we describe a case of a 5-year old, asymptomatically infected with HBV infection two months after chemotherapy for precursor B acute lymphoblastic leukemia (ALL). Although the 5-year old male is South African, his family originated from Guinea. At the end of the one-year follow-up, the infection progressed to chronic HBV infection, with a high viral load. At 36 weeks (8 months) post-treatment with lamivudine (LAM), there was a partial virologic response (PVR) and after 61 weeks (14 months), he was switched to TDF rescue monotherapy. Even with TDF treatment, he still experienced VBT and subsequent PVR. The full-length genome of HBV isolated 78 weeks after the switch to rescue TDF monotherapy was sequenced and belonged to genotype E. In addition to the LAM mutations (rtS256G and rtM267L), missense mutations in B-cell, T-cell, HLA class I and II-restricted epitopes emerged, which were to evade and escape host surveillance, leading to delayed viral clearance, persistence and disease progression. Two further events of VBT occurred between weeks 113 and 141 of TDF rescue-therapy. Viral loads and liver enzymes are normalizing progressively with long-term therapy. CONCLUSION: Although the host immune reconstitution may be delayed, prolonged TDF treatment was effective in treating this pediatric case of HBV infection with VBT and PVR.


Asunto(s)
Hepatitis B Crónica , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Antivirales/uso terapéutico , Niño , Preescolar , ADN Viral/farmacología , ADN Viral/uso terapéutico , Farmacorresistencia Viral , Virus de la Hepatitis B/genética , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Resultado del Tratamiento
15.
BMC Med Educ ; 22(1): 60, 2022 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-35078482

RESUMEN

BACKGROUND: The COVID-19 pandemic brought a new challenge to medical education-health-care students had fewer opportunities to interact with and treat real patients in clinical settings. Interpersonal communication skills are often developed through human interaction and communication in person, and few studies have proposed feasible digital solutions to develop learners' communication skills. Consequently, understanding how medical teachers facilitate and implement online training programmes, with feasible instruments, to enhance students' learning effectiveness when in-person training is not possible is critical. METHODS: By using a convenience sampling method, we recruited 26 health-care students from seven medical schools in Taiwan. Through semistructured interviews and the thematic analysis technique, we analysed the latent learning factors from the experience of implementing the technology-enhanced experiential e-learning tool 'mPath'. RESULTS: Three themes were generated: A) transferring theory into practice, B) increasing authenticity with analytical features, and C) maintaining autonomy with nondirective learning. The features accessibility, flexibility, intractability, and visualisation with the characteristics of remote accessibility and flexibility, repetition and retrospect, feedback requesting, and visualised analytical reports were considered to enhance learning outcomes. CONCLUSION: This study indicated how online training using technology could develop the participants' person-centred communication skills and what features influenced the learning outcomes of social distancing. mPath may be a feasible online learning approach and has provided inspiration for developing health-care students' communication skills when in-person training is not possible.


Asunto(s)
COVID-19 , Instrucción por Computador , Estudiantes de Medicina , Comunicación , Humanos , Pandemias , SARS-CoV-2 , Tecnología
16.
J Formos Med Assoc ; 121(10): 1956-1962, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35151563

RESUMEN

BACKGROUND/PURPOSE: Residents play an important role as teachers of junior colleagues and medical students. Clinical teaching also helps residents in clinical learning. However, the skills required for residents to be competent teachers are rarely described systemically. Beyond the widely adopted six core competencies for postgraduate training by the Accreditation Council for Graduate Medical Education (ACGME), the teaching competencies should be further developed, and the milestones should be clearly defined to serve as better references for resident training programs. METHODS: Twenty members, including five experts from major teaching hospitals across Taiwan and 15 from a public medical center, were invited to a workgroup to collaboratively develop a competency-based framework. The development process was similar to that suggested by the ACGME. The teaching competencies framework were drafted by an experienced physician educator. The draft was sent to each group member, and feedback was collected. Two workgroup meetings were held for consensus formation. The contents of the teaching competencies of residents were confirmed after two rounds of revision. The outline of the framework was also reported at an international meeting in September 2019. RESULTS: Two core competencies, instruction and assessment, with three sub-competencies and 37 milestones, were adopted in the final edition of resident-as-teacher competencies. The sub-competencies were "dissemination of knowledge" and "teaching of procedural skills" for instruction, and "direct observation and feedback" for assessment. CONCLUSION: A competency-based framework for resident-as-teacher was developed. The framework can be applied in combination with other existing competencies for holistic postgraduate training programs.


Asunto(s)
Internado y Residencia , Acreditación , Competencia Clínica , Educación de Postgrado en Medicina , Docentes Médicos , Humanos
17.
Sensors (Basel) ; 22(11)2022 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-35684812

RESUMEN

Falling is a major cause of personal injury and accidental death worldwide, in particular for the elderly. For aged care, a falling alarm system is highly demanded so that medical aid can be obtained immediately when the fall accidents happen. Previous studies on fall detection lacked practical considerations to deal with real-world situations, including the camera's mounting angle, lighting differences between day and night, and the privacy protection for users. In our experiments, IR-depth images and thermal images were used as the input source for fall detection; as a result, detailed facial information is not captured by the system for privacy reasons, and it is invariant to the lighting conditions. Due to the different occurrence rates between fall accidents and other normal activities, supervised learning approaches may suffer from the problem of data imbalance in the training phase. Accordingly, in this study, anomaly detection is performed using unsupervised learning approaches so that the models were trained only with the normal cases while the fall accident was defined as an anomaly event. The proposed system takes sequential frames as the inputs to predict future frames based on a GAN structure, and it provides (1) multi-subject detection, (2) real-time fall detection triggered by motion, (3) a solution to the situation that subjects were occluded after falling, and (4) a denoising scheme for depth images. The experimental results show that the proposed system achieves the state-of-the-art performance and copes with the real-world cases successfully.


Asunto(s)
Iluminación , Privacidad , Anciano , Cara , Humanos , Movimiento (Física)
18.
Opt Express ; 29(3): 4067-4081, 2021 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-33770994

RESUMEN

Förster resonance energy transfer (FRET) from a green-emitting quantum dot (GQD) into a red-emitting quantum dot (RQD) is an important mechanism in a multiple-color conversion process, particularly under the surface plasmon (SP) coupling condition for enhancing color conversion efficiency. Here, the dependencies of FRET efficiency on the relative concentrations of GQD and RQD in their mixtures and their surface molecule coatings for controlling surface charges are studied. Also, the SP coupling effects induced by two kinds of Ag nanoparticles on the emission behaviors of GQD and RQD are demonstrated, particularly when FRET is involved in the coupling process. FRET efficiency is reduced under the SP coupling condition. SP coupling can enhance the color conversion efficiency of either GQD or RQD. The combination of SP coupling and FRET can be used for controlling the relative converted light intensities in a multiple-color conversion process.

19.
Nanotechnology ; 32(29)2021 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-33848997

RESUMEN

Rhodamine 6G (R6G) molecules linked CdZnSeS/ZnS green-emitting quantum dots (QDs) are self-assembled onto Ag nanoparticles (NPs) for studying the surface plasmon (SP) coupling effect on the Förster resonance energy transfer (FRET) process from QD into R6G. SP coupling can enhance the emission efficiency of QD such that FRET has to compete with QD emission for transferring energy into R6G. It is found that FRET efficiency is reduced under the SP coupling condition. Although R6G emission efficiency can also be enhanced through SP coupling when it is directly linked onto Ag NP, the enhancement decreases when R6G is linked onto QD and then the QD-R6G complex is self-assembled onto Ag NP. In particular, R6G emission efficiency can be reduced through SP coupling when the number of R6G molecules linked onto a QD is high. A rate-equation model is built for resembling the measured photoluminescence decay profiles and providing us with more detailed explanations for the observed FRET and SP coupling behaviors.

20.
Nanotechnology ; 32(13): 135206, 2021 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-33271517

RESUMEN

By forming nanodisk (ND) structures on a blue-emitting InGaN/GaN quantum-well (QW) template, the QWs become close to the red-emitting quantum dots (QDs) and Ag nanoparticles (NPs) attached onto the sidewalls of the NDs such that Förster resonance energy transfer (FRET) and surface plasmon (SP) coupling can occur to enhance the efficiency of blue-to-red color conversion. With a larger ND height, more QWs are exposed to open air on the sidewall for more QD/Ag NP attachment through QD self-assembly and Ag NP drop casting such that the FRET and SP coupling effects, and hence the color conversion efficiency can be enhanced. A stronger FRET process leads to a longer QD photoluminescence (PL) decay time and a shorter QW PL decay time. It is shown that SP coupling can enhance the FRET efficiency.

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