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1.
Nucleic Acids Res ; 52(17): 10645-10653, 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39011881

RESUMO

RNA methylation adjacent to the 5' cap plays a critical role in controlling mRNA stability and protein synthesis. In trypanosomes the 5'-terminus of mRNA is protected by hypermethylated cap 4. Trypanosomes encode a cytoplasmic recapping enzyme TbCe1 which possesses an RNA kinase and guanylyltransferase activities that can convert decapped 5'-monophosphate-terminated pRNA into GpppRNA. Here, we demonstrated that the RNA kinase activity is stimulated by two orders of magnitude on a hypermethylated pRNA derived from cap 4. The N6, N6-2'-O trimethyladenosine modification on the first nucleotide was primarily accountable for enhancing both the RNA kinase and the guanylyltransferase activity of TbCe1. In contrast, N6 methyladenosine severely inhibits the guanylyltransferase activity of the mammalian capping enzyme. Furthermore, we showed that TbCmt1 cap (guanine N7) methyltransferase was localized in the cytoplasm, and its activity was also stimulated by hypermethylation at 2'-O ribose, suggesting that TbCe1 and TbCmt1 act together as a recapping enzyme to regenerate translatable mRNA from decapped mRNA. Our result establishes the functional role of cap 4 hypermethylation in recruitment and activation of mRNA recapping pathway. Methylation status at the 5'-end of transcripts could serve as a chemical landmark to selectively regulate the level of functional mRNA by recapping enzymes.


Assuntos
Nucleotidiltransferases , Proteínas de Protozoários , Capuzes de RNA , RNA Mensageiro , Trypanosoma brucei brucei , Capuzes de RNA/metabolismo , Capuzes de RNA/genética , Trypanosoma brucei brucei/genética , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Metilação , Nucleotidiltransferases/metabolismo , Nucleotidiltransferases/genética , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Metiltransferases/metabolismo , Metiltransferases/genética , Citoplasma/metabolismo , Adenosina/análogos & derivados , Adenosina/metabolismo , Adenosina/genética
2.
Clin Radiol ; 79(11): e1366-e1371, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39266371

RESUMO

AIM: This study evaluated the readability of existing patient education materials and explored the potential of generative AI tools, such as ChatGPT-4 and Google Gemini, to simplify these materials to a sixth-grade reading level, in accordance with guidelines. MATERIALS AND METHODS: Seven patient education documents were selected from a major radiology group. ChatGPT-4 and Gemini were provided the documents and asked to reformulate to target a sixth-grade reading level. Average reading level (ARL) and proportional word count (PWC) change were calculated, and a 1-sample t-test was conducted (p=0.05). Three radiologists assessed the materials on a Likert scale for appropriateness, relevance, clarity, and information retention. RESULTS: The original materials had an ARL of 11.72. ChatGPT ARL was 7.32 ± 0.76 (6/7 significant) and Gemini ARL was 6.55 ± 0.51 (7/7 significant). ChatGPT reduced word count by 15% ± 7%, with 95% retaining at least 75% of information. Gemini reduced word count by 33% ± 7%, with 68% retaining at least 75% of information. ChatGPT outputs were more appropriate (95% vs. 57%), clear (92% vs. 67%), and relevant (95% vs. 76%) than Gemini. Interrater agreement was significantly different for ChatGPT (0.91) than for Gemini (0.46). CONCLUSION: Generative AI significantly enhances the readability of patient education materials, which did not achieve the recommended sixth-grade ARL. Radiologist evaluations confirmed the appropriateness and relevance of the AI-simplified texts. This study emphasizes the capabilities of generative AI tools and the necessity for ongoing expert review to maintain content accuracy and suitability.


Assuntos
Compreensão , Educação de Pacientes como Assunto , Radiologia , Humanos , Educação de Pacientes como Assunto/métodos , Radiologia/educação , Inteligência Artificial , Letramento em Saúde , Materiais de Ensino/normas
3.
J Dairy Sci ; 107(1): 438-458, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37690712

RESUMO

In this single cohort study, we investigated associations between the concentrations of a suite of serum biomarkers measured in the first 30 d of lactation and subsequent reproductive performance measured as mating start date to conception intervals, in pasture-based Holstein cows. A secondary objective was to examine associations between biomarker concentrations and 305-d milk yield to assess whether any positive associations between biomarker concentration and reproductive performance were explained by reduced milk production. The data used had been collected as part of an ongoing project from 2017 to 2020 to compile a data set from a large population of lactating dairy cows. Biomarkers measured were those associated with energy balance (ß-hydroxybutyrate [BHB] and nonesterified fatty acids [NEFA]), protein nutritional status (urea and albumin), immune status (globulin, albumin to globulin ratio and haptoglobin), and macromineral status (calcium and magnesium). Associations between biomarker concentrations and mating start date to conception interval were investigated using Cox proportional hazard models, using between 634 and 1,121 lactations (varying by biomarker) from 632 to 1,103 cows and 11 to 17 mating periods from 10 to 13 herds. Based on hazard ratio (HR) estimates and associated 95% confidence intervals (CI), hazard of conception on any particular day of the herds' mating periods was positively associated with the concentrations of albumin (HR = 1.09; 95% CI: 1.05-1.12), albumin to globulin ratio (HR = 2.82; 95% CI: 1.66-4.79), calcium (HR = 2.01; 95% CI: 1.18-3.43), and magnesium (HR = 2.17; 95% CI: 1.01-4.66), and negatively associated with globulin concentration (HR = 0.98; 95% CI: 0.97 to 1.00). There was also some evidence that NEFA concentration was negatively associated (HR = 0.76; 95% CI: 0.57 to 1.01), and urea concentration positively associated (HR = 1.05; 95% CI: 0.99 to 1.11), with reproductive performance, but no evidence that BHB and haptoglobin concentrations were associated with reproductive performance. Except for NEFA, presence and direction of the associations between the biomarker and milk yield were not discordant with that for reproductive performance. Also, except for NEFA, we found no substantial evidence of nonlinear relationships between biomarker concentration and either reproductive performance or milk yield. Correlations between biomarker concentrations were generally weak, indicating that multibiomarker panels may collectively predict reproductive performance better than any single biomarker. We noted substantial variation in the concentrations of all biomarkers within, and for some biomarkers, between herd-year groups. Collectively, these results indicate that there may be scope to improve biomarker concentrations through nutritional, management, and genetic interventions, and by association, reproductive performance and milk yield may also improve.


Assuntos
Lactação , Leite , Humanos , Feminino , Bovinos , Animais , Leite/metabolismo , Ácidos Graxos não Esterificados , Estudos de Coortes , Cálcio/metabolismo , Haptoglobinas/metabolismo , Magnésio/metabolismo , Biomarcadores/metabolismo , Austrália , Albuminas/metabolismo , Ureia/metabolismo , Ácido 3-Hidroxibutírico
4.
J Dairy Sci ; 107(7): 4461-4475, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38331182

RESUMO

Grain mixes varying in proportions of wheat grain, barley grain, canola meal, and corn grain were fed to grazing dairy cows in early lactation to determine the contribution of canola meal and corn grain to milk yield, BW, BCS, eating behavior, and blood serum metabolite concentrations. The experiment used 80 multiparous, seasonally calving Holstein-Friesian dairy cows during the first 100 d of lactation, the treatment period, and over the subsequent carryover period of 100 d, during which all cows were fed a common diet. Cows were divided into 4 cohorts (blocks) based on calving date and within each cohort, 5 cows were randomly allocated to each of the 4 treatments. Dietary treatments included disc-milled grain mixes comprising (on a DM basis) (1) a control treatment of wheat (25%) and barley (75%); (2) wheat (25%), barley (50%), and canola meal (25%); (3) wheat (25%), barley (50%), and corn (25%), and (4) wheat (25%), barley (25%), canola meal (25%), and corn (25%). Treatment diets were introduced at 19 DIM ± 4.7 d, which included a 7-d adaptation period and were applied up until 100 DIM. Each grain mix was fed at 9 kg of DM/cow per day, offered twice daily, in equal proportions in the parlor at milking times. In addition to the grain mix, all cows grazed perennial ryegrass pasture at a daily allowance of ∼35 kg of DM/cow per day (measured to ground level). Results were analyzed in terms of corn and canola presence or absence in the diet. Including canola meal in grain mixes increased grain intake and pasture intake by 0.6 and 2.1 kg of DM/cow per day, respectively, resulting in an increased milk yield of 2.6 kg/cow per day during the first 100 d of lactation. Including canola meal also increased yields of milk fat and protein, and concentrations of milk fat, as well as increasing mean BW and BCS over the 100 d. The inclusion of canola meal in the grain mixes also resulted in greater blood serum BHB and urea concentrations, compared with feeding grain mixes that did not contain canola meal. The inclusion of corn grain provided no milk production benefits and did not change BW, BCS, or any feeding behavior variables. There were no carryover effects on milk production from either canola meal or corn grain after the treatment period. In summary, the results demonstrate that the provision of canola meal in grain mixes can improve milk production and increase mean BCS. Further, there are no benefits to milk yield when a proportion of barley is substituted for corn, in a wheat and barley grain mix fed to grazing dairy cows in early lactation. However, these results are dependent on the level of inclusion and the feeding system employed.


Assuntos
Ração Animal , Dieta , Lactação , Leite , Zea mays , Animais , Bovinos , Feminino , Leite/metabolismo , Leite/química , Dieta/veterinária , Grão Comestível
5.
Ann Oncol ; 34(3): 251-261, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36535566

RESUMO

BACKGROUND: Pembrolizumab previously demonstrated robust antitumor activity and manageable safety in a phase Ib study of patients with heavily pretreated, programmed death ligand 1 (PD-L1)-positive, recurrent or metastatic nasopharyngeal carcinoma (NPC). The phase III KEYNOTE-122 study was conducted to further evaluate pembrolizumab versus chemotherapy in patients with platinum-pretreated, recurrent and/or metastatic NPC. Final analysis results are presented. PATIENTS AND METHODS: KEYNOTE-122 was an open-label, randomized study conducted at 29 sites, globally. Participants with platinum-pretreated recurrent and/or metastatic NPC were randomly assigned (1 : 1) to pembrolizumab or chemotherapy with capecitabine, gemcitabine, or docetaxel. Randomization was stratified by liver metastasis (present versus absent). The primary endpoint was overall survival (OS), analyzed in the intention-to-treat population using the stratified log-rank test (superiority threshold, one-sided P = 0.0187). Safety was assessed in the as-treated population. RESULTS: Between 5 May 2016 and 28 May 2018, 233 participants were randomly assigned to treatment (pembrolizumab, n = 117; chemotherapy, n = 116); Most participants (86.7%) received study treatment in the second-line or later setting. Median time from randomization to data cut-off (30 November 2020) was 45.1 months (interquartile range, 39.0-48.8 months). Median OS was 17.2 months [95% confidence interval (CI) 11.7-22.9 months] with pembrolizumab and 15.3 months (95% CI 10.9-18.1 months) with chemotherapy [hazard ratio, 0.90 (95% CI 0.67-1.19; P = 0.2262)]. Grade 3-5 treatment-related adverse events occurred in 12 of 116 participants (10.3%) with pembrolizumab and 49 of 112 participants (43.8%) with chemotherapy. Three treatment-related deaths occurred: 1 participant (0.9%) with pembrolizumab (pneumonitis) and 2 (1.8%) with chemotherapy (pneumonia, intracranial hemorrhage). CONCLUSION: Pembrolizumab did not significantly improve OS compared with chemotherapy in participants with platinum-pretreated recurrent and/or metastatic NPC but did have manageable safety and a lower incidence of treatment-related adverse events.


Assuntos
Neoplasias Nasofaríngeas , Platina , Humanos , Neoplasias Nasofaríngeas/tratamento farmacológico , Anticorpos Monoclonais Humanizados , Docetaxel , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
6.
Hong Kong Med J ; 29(2): 105-111, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36990676

RESUMO

INTRODUCTION: This study aims to determine the outcomes of stereotactic body radiotherapy (SBRT) for liver metastases in patients not eligible for surgery. METHODS: This study included 31 consecutive patients with unresectable liver metastases who received SBRT between January 2012 and December 2017; 22 patients had primary colorectal cancer and nine patients had primary non-colorectal cancer. Treatments ranged from 24 Gy to 48 Gy in 3 to 6 fractions over 1 to 2 weeks. Survival, response rates, toxicities, clinical characteristics, and dosimetric parameters were evaluated. Multivariate analysis was performed to identify significant prognostic factors for survival. RESULTS: Among these 31 patients, 65% had received at least one prior regimen of systemic therapy for metastatic disease, whereas 29% had received chemotherapy for disease progression or immediately after SBRT. The median follow-up interval was 18.9 months; actuarial in-field local control rates at 1, 2, and 3 years after SBRT were 94%, 55%, and 42%, respectively. The median survival duration was 32.9 months; 1-year, 2-year, and 3-year actuarial survival rates were 89.6%, 57.1%, and 46.2%, respectively. The median time to progression was 10.9 months. Stereotactic body radiotherapy was well-tolerated, with grade 1 toxicities of fatigue (19%) and nausea (10%). Patients who received post-SBRT chemotherapy had significant longer overall survival (P=0.039 for all patients and P=0.001 for patients with primary colorectal cancer). CONCLUSION: Stereotactic body radiotherapy can be safely administered to patients with unresectable liver metastases, and it may delay the need for chemotherapy. This treatment should be considered for selected patients with unresectable liver metastases.


Assuntos
Neoplasias Hepáticas , Radiocirurgia , Humanos , Radiocirurgia/efeitos adversos , Prognóstico , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/patologia , Estudos Retrospectivos
7.
Epidemiol Mikrobiol Imunol ; 72(4): 213-220, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38242706

RESUMO

BACKGROUND AND AIM: Haemolytic uraemic syndrome (HUS) is a triad of haemolytic anaemia, thrombocytopaenia, and acute kidney injury. It is a leading cause of acute kidney injury in children and has a high rate of long-term sequelae. Streptococcus pneumoniae-associated HUS (SpHUS) is a rare complication from pneumococcal disease. This article aims to systematically review SpHUS following the global introduction of pneumococcal conjugate vaccines (PCVs). MATERIAL AND METHODS: A comprehensive literature search was conducted in MEDLINE, EMBASE, and the Cochrane library from 1st January 2000 to 13th April 2022. RESULTS: Thirteen studies were included in this review, involving a total of 7,177 children with HUS, of which 336 cases were associated with Streptococcus pneumoniae. SpHUS accounted for 4.8% of all HUS cases, in which most patients were younger than 24 months old. Nine studies (80.4%, 281) were during the country's PCV era, whereas 4 studies (19.6%, 66) were before the introduction of PCV into the national vaccination programme. Pneumonia was the commonest clinical presentation (77.3%; 75/97), followed by septicaemia (33.0%; 32/97), and meningitis (29.9%; 29/97). Most cases presenting with pneumonia were complicated by empyema or pleural effusion (54.4%, n=49/90). Only 5 studies reported the isolated serotypes, with the most prevalent serotype being 19A (44.4%, n=20/45), followed by serotype 3 (17.8%, n = 8/45) and 7F (6.7%, n = 3/45). Of those reporting fatality, there were 12 deaths with a fatality rate of 9.8% (n = 12/122). CONCLUSION: SpHUS is rare, but commonly presents in children younger than 2 years old. There remains a high risk of long-term complications and relatively high mortality rate even in the era of conjugate vaccines.


Assuntos
Injúria Renal Aguda , Síndrome Hemolítico-Urêmica , Infecções Pneumocócicas , Pneumonia , Criança , Humanos , Lactente , Pré-Escolar , Streptococcus pneumoniae , Vacinas Pneumocócicas , Infecções Pneumocócicas/complicações , Infecções Pneumocócicas/epidemiologia , Sorogrupo , Síndrome Hemolítico-Urêmica/complicações , Síndrome Hemolítico-Urêmica/epidemiologia , Injúria Renal Aguda/complicações
8.
Anim Genet ; 53(1): 166-170, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34910829

RESUMO

We developed a high-resolution and comprehensive typing method for swine leukocyte antigen 3 (SLA-3), an MHC class I gene, employing locus-specific genomic PCR followed by subsequent direct sequencing. A total of 292 individuals from nine pure, one cross-breed and six cell lines were successfully typed. A total of 21 SLA-3 alleles were identified, of which four were found to be novel alleles. However, the allelic diversity of SLA-3 was lower than that of previously reported class I genes, SLA-1 and -2. More SLA-3 alleles were observed in the Landrace and Yorkshire breeds than the other breeds. SLA-3*04:01 was identified in seven out of nine breeds and was the most widely distributed allele across all breeds. Therefore, the typing method reported in this study completes our efforts to develop high-resolution typing methods for major SLA molecules, facilitating the combined analysis of major SLA genes from field samples, which is important to understand the relationship between the adaptive immune responses against pathogens and the immunogenetic makeup of an individual.


Assuntos
Técnicas de Genotipagem/veterinária , Antígenos de Histocompatibilidade Classe I/genética , Análise de Sequência de DNA/veterinária , Sus scrofa/genética , Animais , Análise de Sequência de DNA/métodos
9.
BMC Med Ethics ; 23(1): 105, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36319979

RESUMO

BACKGROUND: Residual dried blood spots (rDBS) from newborn screening programmes represent a valuable resource for medical research, from basic sciences, through clinical to public health. In Hong Kong, there is no legislation for biobanking. Parents' view on the retention and use of residual newborn blood samples could be cultural-specific and is important to consider for biobanking of rDBS. OBJECTIVE: To study the views and concerns on long-term storage and secondary use of rDBS from newborn screening programmes among Hong Kong Chinese parents. METHODS: A mixed-method approach was used to study the views and concerns on long-term storage and secondary use of rDBS from newborn screening programmes among Hong Kong Chinese parents of children 0-3 years or expecting parents through focus groups (8 groups; 33 participants) and a survey (n = 1012, 85% mothers) designed with insights obtained from the focus groups. We used framework analysis to summarise the themes as supportive factors, concerns and critical arguments for retention and secondary use of rDBS from focus group discussion. We used multiple logistic regression to assess factors associated with support for retention and secondary use of rDBS in the survey. RESULTS: Both in focus groups and survey, majority of parents were not aware of the potential secondary use of rDBS. Overall secondary use of rDBS in medical research was well accepted by a large proportion of Hong Kong parents, even if all potential future research could not be specified in a broad consent. However parents were concerned about potential risks of biobanking rDBS including leaking of data and mis-use of genetic information. Parents wanted to be asked for permission before rDBS are stored and mainly did not accept an "opt-out" approach. The survey showed that parents born in mainland China, compared to Hong Kong born parents, had lower awareness of newborn screening but higher support in biobanking rDBS. Higher education was associated with support in rDBS biobanking only among fathers. CONCLUSION: Long-term storage and secondary use of rDBS from newborn screening for biomedical research and a broad consent for biobanking of rDBS are generally acceptable to Hong Kong parents given their autonomy is respected and their privacy is protected, highlighting the importance of an accountable governance and a transparent access policy for rDBS biobanks.


Assuntos
Bancos de Espécimes Biológicos , Triagem Neonatal , Recém-Nascido , Criança , Feminino , Humanos , Triagem Neonatal/métodos , Hong Kong , Pais , Mães
10.
Hong Kong Med J ; 28(1): 64-72, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-33518531

RESUMO

Intensive care is expensive, and the numbers of intensive care unit (ICU) beds and trained specialist medical staff able to provide services in Hong Kong are limited. The most recent increase in coronavirus disease 2019 (COVID-19) infections over July to August 2020 resulted in more than 100 new cases per day for a prolonged period. The increased numbers of critically ill patients requiring ICU admission posed a capacity challenge to ICUs across the territory, and it may be reasonably anticipated that should a substantially larger outbreak occur, ICU services will be overwhelmed. Therefore, a transparent and fair prioritisation process for decisions regarding patient ICU admission is urgently required. This triage tool is built on the foundation of the existing guidelines and framework for admission, discharge, and triage that inform routine clinical practice in Hospital Authority ICUs, with the aim of achieving the greatest benefit for the greatest number of patients from the available ICU resources. This COVID-19 Crisis Triage Tool is expected to provide structured guidance to frontline doctors on how to make triage decisions should ICU resources become overwhelmed by patients requiring ICU care, particularly during the current COVID-19 pandemic. The triage tool takes the form of a detailed decision aid algorithm based on a combination of established prognostic scores, and it should increase objectivity and transparency in triage decision making and enhance decision-making consistency between doctors within and across ICUs in Hong Kong. However, it remains an aid rather than a complete substitute for the carefully considered judgement of an experienced intensive care clinician.


Assuntos
COVID-19 , Hospitalização , Triagem , Adulto , COVID-19/epidemiologia , Surtos de Doenças , Hong Kong/epidemiologia , Humanos , Unidades de Terapia Intensiva , Pandemias , SARS-CoV-2 , Triagem/métodos
11.
Malays J Pathol ; 44(2): 261-267, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36043589

RESUMO

INTRODUCTION: Macroprolactinaemia is usually detected by polyethylene glycol (PEG) precipitation in clinical laboratories. Laboratory data on prolactin and macroprolactin screening by PEG precipitation in a tertiary hospital were reviewed in order to revise the local policy for reflex screening and reporting of macroprolactin in patients with hyperprolactinaemia. MATERIALS AND METHODS: Paired prolactin results from 464 patients before and after PEG precipitation, either requested by a clinician or performed as a reflex test, were retrieved and reviewed. RESULTS: Recovery of prolactin after PEG treatment was highly variable (3.7 to 97.7%). The distribution of prolactin recovery percentages after PEG precipitation in patients with true hyperprolactinaemia was markedly different from that in patients without true hyperprolactinaemia. The proportion of patients with true hyperprolactinaemia increased gradually with increasing pre-PEG prolactin concentrations; the reverse was true with macroprolactinaemia. Five patients (1.1%) were found to have co-existing macroprolactinaemia and true hyperprolactinaemia. CONCLUSION: Results from this retrospective study indicate that macroprolactinaemia is common and can be present even in patients with very high serum prolactin concentrations. There is no cut-off limit for pre-PEG serum prolactin concentration that can totally exclude macroprolactinaemia. Moreover, co-existence of true hyperprolactinaemia and macroprolactinaemia in the same patient is not a rare phenomenon. Post-PEG prolactin concentration and percentage recovery should be reported together to guide the interpretation and management of hyperprolactinaemia.


Assuntos
Hiperprolactinemia , Humanos , Hiperprolactinemia/diagnóstico , Programas de Rastreamento , Polietilenoglicóis , Prolactina , Estudos Retrospectivos
12.
Malays J Pathol ; 44(1): 61-66, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35484887

RESUMO

Merkel cell carcinoma (MCC) is a rare malignant cutaneous neuroendocrine tumour affecting mainly elderly patients and is more common in the West than in Asia. It is associated with Merkel cell polyomavirus (MCPyV), immunosuppression, and ultraviolet light. In this study, we retrospectively investigated the first series of MCC from Taiwan and identified 19 cases from three tertiary centres. All patients were males with a median age of 67.5. Twelve (63%) cases occurred in the extremities, with one unique case presenting initially as nodal metastasis of unknown primary. Immunohistochemically, the great majority of tumours expressed CK20 (89%), synaptophysin (89%), and INSM1 (84%), with none positive for TTF1. Eleven (58%) cases were positive for MCPyV by immunohistochemistry (clone CM2B4). All patients were treated with excision, including four with additional radiotherapy and one with radiotherapy and chemotherapy. Nodal status and treatment modalities significantly affected survival. The median survival time of MCPyV-positive cases was much longer than the negative cases (median 40 vs. 10 months). In summary, we presented the first report on the clinicopathological features of MCC in Taiwan, with 58% cases associated with MCPyV. The prognosis of patients with MCPyV-positive tumours was better than those negative for MCPyV.


Assuntos
Carcinoma de Célula de Merkel , Poliomavírus das Células de Merkel , Infecções por Polyomavirus , Neoplasias Cutâneas , Idoso , Carcinoma de Célula de Merkel/patologia , Feminino , Humanos , Masculino , Infecções por Polyomavirus/complicações , Infecções por Polyomavirus/patologia , Prognóstico , Proteínas Repressoras , Estudos Retrospectivos , Neoplasias Cutâneas/patologia , Taiwan
13.
J Biol Chem ; 295(27): 9076-9086, 2020 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-32381506

RESUMO

RNA triphosphatase catalyzes the first step in mRNA cap formation, hydrolysis of the terminal phosphate from the nascent mRNA transcript. The RNA triphosphatase from the protozoan parasite Trypanosoma cruzi, TcCet1, belongs to the family of triphosphate tunnel metalloenzymes (TTMs). TcCet1 is a promising antiprotozoal drug target because the mechanism and structure of the protozoan RNA triphosphatases are completely different from those of the RNA triphosphatases found in mammalian and arthropod hosts. Here, we report several crystal structures of the catalytically active form of TcCet1 complexed with a divalent cation and an inorganic tripolyphosphate in the active-site tunnel at 2.20-2.51 Å resolutions. The structures revealed that the overall structure, the architecture of the tunnel, and the arrangement of the metal-binding site in TcCet1 are similar to those in other TTM proteins. On the basis of the position of three sulfate ions that cocrystallized on the positively charged surface of the protein and results obtained from mutational analysis, we identified an RNA-binding site in TcCet1. We conclude that the 5'-end of the triphosphate RNA substrate enters the active-site tunnel directionally. The structural information reported here provides valuable insight into designing inhibitors that could specifically block the entry of the triphosphate RNA substrate into the TTM-type RNA triphosphatases of T. cruzi and related pathogens.


Assuntos
Hidrolases Anidrido Ácido/ultraestrutura , Capuzes de RNA/metabolismo , RNA/metabolismo , Hidrolases Anidrido Ácido/metabolismo , Sequência de Aminoácidos , Sítios de Ligação/fisiologia , Domínio Catalítico/fisiologia , Cinética , Metaloproteínas/metabolismo , Modelos Moleculares , RNA/ultraestrutura , Processamento Pós-Transcricional do RNA , RNA Mensageiro/metabolismo , Homologia de Sequência de Aminoácidos , Trypanosoma cruzi/metabolismo , Trypanosoma cruzi/ultraestrutura
14.
Br Med Bull ; 138(1): 41-57, 2021 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-33884400

RESUMO

INTRODUCTION: This is an overall review on mindfulness-based interventions (MBIs). SOURCES OF DATA: We identified studies in PubMed, EMBASE, CINAHL, PsycINFO, AMED, Web of Science and Google Scholar using keywords including 'mindfulness', 'meditation', and 'review', 'meta-analysis' or their variations. AREAS OF AGREEMENT: MBIs are effective for improving many biopsychosocial conditions, including depression, anxiety, stress, insomnia, addiction, psychosis, pain, hypertension, weight control, cancer-related symptoms and prosocial behaviours. It is found to be beneficial in the healthcare settings, in schools and workplace but further research is warranted to look into its efficacy on different problems. MBIs are relatively safe, but ethical aspects should be considered. Mechanisms are suggested in both empirical and neurophysiological findings. Cost-effectiveness is found in treating some health conditions. AREAS OF CONTROVERSY: Inconclusive or only preliminary evidence on the effects of MBIs on PTSD, ADHD, ASD, eating disorders, loneliness and physical symptoms of cardiovascular diseases, diabetes, and respiratory conditions. Furthermore, some beneficial effects are not confirmed in subgroup populations. Cost-effectiveness is yet to confirm for many health conditions and populations. GROWING POINTS: Many mindfulness systematic reviews and meta-analyses indicate low quality of included studies, hence high-quality studies with adequate sample size and longer follow-up period are needed. AREAS TIMELY FOR DEVELOPING RESEARCH: More research is needed on online mindfulness trainings and interventions to improve biopsychosocial health during the COVID-19 pandemic; Deeper understanding of the mechanisms of MBIs integrating both empirical and neurophysiological findings; Long-term compliance and effects of MBIs; and development of mindfulness plus (mindfulness+) or personalized mindfulness programs to elevate the effectiveness for different purposes.


Assuntos
COVID-19/psicologia , COVID-19/terapia , Atenção Plena , COVID-19/epidemiologia , Humanos
15.
Opt Express ; 29(5): 6824-6833, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33726194

RESUMO

We have fabricated a Si racetrack optical modulator based on a III-V/Si hybrid metal-oxide-semiconductor (MOS) capacitor. The III-V/Si hybrid MOS optical phase shifter was integrated to a Si racetrack resonator with a coupling length of 200 µm and a coupling gap of 700 nm. The fabricated Si racetrack resonator demonstrated a small VπL of 0.059 Vcm. For 10-dB optical intensity modulation, the Si racetrack resonator showed a 60% smaller driving voltage than a Mach-Zehnder interferometer modulator with the same phase shifter, leading to a better balance between high energy efficiency and large modulation bandwidth.

16.
Osteoporos Int ; 32(5): 961-970, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33104822

RESUMO

Bone mineral density (BMD) may be increased due to vertebral compression fractures (VCF). Our study showed trabecular bone scores (TBS) was less affected than BMD by fractured vertebrae. The TBS of most compression fractures, including old and recent VCF with mild or moderate deformity and old VCF with severe deformity, could still be used in predicting fracture risk. INTRODUCTION: Trabecular bone score (TBS), a noninvasive tool estimating bone microarchitecture, provides complementary information to lumbar spine bone mineral density (BMD). Lumbar spine BMD might be increased due to both degenerative disease and vertebral compression fractures (VCF). Lumbar spine TBS has been confirmed not influenced by osteoarthrosis, but the effects of VCF are still not been well evaluated. This study aimed to investigate whether lumbar spine TBS was affected by fractured vertebrae. METHODS: We studied postmenopausal women and men above 50 years old who underwent DXA between January 1, 2017, and May 31, 2019. By calculating the difference of BMD and TBS between L1 and the mean of L2-3, the study compared the difference of values between the control group and fracture group to determine the effects of fractured vertebrae on BMD and TBS. RESULTS: A total of 377 participants were enrolled with 202 in the control group (157 females; age: 68.06 ± 6.47 years) and 175 in the fracture group (147 females; age: 71.71 ± 9.44 years). The mean BMD of the L1 vertebrae in the fracture group was significantly higher than that in the control group (p < 0.0001). There was no significant difference between the mean differences of TBS between L1 and the means of L2-3 vertebrae in the control group and the most compression fractures, including old and recent VCF with mild or moderate deformity and old VCF with severe deformity. CONCLUSION: Lumbar spine TBS, unlike BMD, is less affected by fractured vertebrae. The TBS of most compression fractures, including old and recent VCF with mild or moderate deformity and old VCF with severe deformity, could still be used in predicting fracture risk.


Assuntos
Fraturas por Compressão , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Absorciometria de Fóton , Idoso , Idoso de 80 Anos ou mais , Densidade Óssea , Osso Esponjoso/diagnóstico por imagem , Feminino , Fraturas por Compressão/diagnóstico por imagem , Fraturas por Compressão/etiologia , Humanos , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Fraturas por Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/etiologia , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/etiologia
17.
Nanotechnology ; 32(14): 145717, 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33463532

RESUMO

High-quality van der Waals heterostructures assembled from hBN-encapsulated monolayer transition metal dichalcogenides enable observations of subtle optical and spin-valley properties whose identification was beyond the reach of structures exfoliated directly on standard SiO2/Si substrates. Here, we describe different van der Waals heterostructures based on uncapped single-layer MoS2 stacked onto hBN layers of different thicknesses and hBN-encapsulated monolayers. Depending on the doping level, they reveal the fine structure of excitonic complexes, i.e. neutral and charged excitons. In the emission spectra of a particular MoS2/hBN heterostructure without an hBN cap we resolve two trion peaks, T1 and T2, energetically split by about 10 meV, resembling the pair of singlet and triplet trion peaks (T S and T T ) in tungsten-based materials. The existence of these trion features suggests that monolayer MoS2 has a dark excitonic ground state, despite having a 'bright' single-particle arrangement of spin-polarized conduction bands. In addition, we show that the effective excitonic g-factor significantly depends on the electron concentration and reaches the lowest value of -2.47 for hBN-encapsulated structures, which reveals a nearly neutral doping regime. In the uncapped MoS2 structures, the excitonic g-factor varies from -1.15 to -1.39 depending on the thickness of the bottom hBN layer and decreases as a function of rising temperature.

18.
Med J Malaysia ; 75(2): 167-168, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32281600

RESUMO

Intestinal obstruction in infancy due to duplication cyst is rare. This is a case of a three-month old boy presented to the hospital with symptoms and signs of intermittent intestinal obstruction for three-week duration. Investigation with ultrasound revealed a small bowel duplication cyst. Patient underwent successful segmental jejunal resection and made an uneventful recovery. He made significant weight gain at one-year follow-up. The diagnostic approach to infant with intestinal obstruction is described with special emphasis on ultrasonographic features of jejunal duplication cyst.


Assuntos
Cistos , Obstrução Intestinal/diagnóstico por imagem , Obstrução Intestinal/cirurgia , Humanos , Lactente , Intestino Delgado , Malásia , Masculino , Resultado do Tratamento , Ultrassonografia
20.
Clin Radiol ; 74(5): 329-337, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30898383

RESUMO

The hype over artificial intelligence (AI) has spawned claims that clinicians (particularly radiologists) will become redundant. It is still moot as to whether AI will replace radiologists in day-to-day clinical practice, but more AI applications are expected to be incorporated into the workflows in the foreseeable future. These applications could produce significant ethical and legal issues in healthcare if they cause abrupt disruptions to its contextual integrity and relational dynamics. Sustaining trust and trustworthiness is a key goal of governance, which is necessary to promote collaboration among all stakeholders and to ensure the responsible development and implementation of AI in radiology and other areas of clinical work. In this paper, the nature of AI governance in biomedicine is discussed along with its limitations. It is argued that radiologists must assume a more active role in propelling medicine into the digital age. In this respect, professional responsibilities include inquiring into the clinical and social value of AI, alleviating deficiencies in technical knowledge in order to facilitate ethical evaluation, supporting the recognition, and removal of biases, engaging the "black box" obstacle, and brokering a new social contract on informational use and security. In essence, a much closer integration of ethics, laws, and good practices is needed to ensure that AI governance achieves its normative goals.


Assuntos
Inteligência Artificial/tendências , Processamento de Imagem Assistida por Computador/métodos , Papel Profissional , Radiologia/métodos , Humanos , Processamento de Imagem Assistida por Computador/tendências , Radiologistas , Radiologia/tendências
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