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1.
J Viral Hepat ; 31(7): 391-403, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38654623

RESUMO

In Vietnam and the Philippines, viral hepatitis is the leading cause of cirrhosis and liver cancer. This study aims to understand the barriers and enablers of people receiving care for hepatitis B and C to support both countries' efforts to eliminate viral hepatitis as a public health threat by 2030. Retrospective, semi-structured interviews were conducted with a purposive, quota-based sample of 63 people living with hepatitis B or C in one province of Vietnam and one region of the Philippines. A rapid deductive approach to thematic analysis produced key findings among the three phases of care: (1) pre-awareness and testing, (2) linkage and treatment initiation and (3) ongoing treatment and recovery. The research found that participants followed five typical journeys, from a variety of entry points. Barriers during the pre-awareness and testing phase included limited awareness about hepatitis and its management, stigma and psychological impacts. Enablers included being familiar with the health system and/or patients benefiting from social connections within the health systems. During the linkage and treatment initiation phase, barriers included difficult physical access, complex navigation and inadequate counselling. In this phase, family support emerged as a critical enabler. During the ongoing treatment and recovery phase, the cost of care and socially and culturally informed perceptions of the disease and medication use were both barriers and enablers. Exploring peoples' journeys with hepatitis B and C in Vietnam and the Philippines revealed many similarities despite the different cultural and health system contexts. Insights from this study may help generate a contextualized, people-centred evidence base to inform the design and improvement of primary care services for hepatitis in both research sites.


Assuntos
Acessibilidade aos Serviços de Saúde , Humanos , Vietnã/epidemiologia , Filipinas/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Idoso , Hepatite B , Entrevistas como Assunto , Adulto Jovem , Hepatite C/epidemiologia , Hepatite C/tratamento farmacológico
2.
Plant Biotechnol J ; 19(2): 230-239, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33047464

RESUMO

Gene editing and/or allele introgression with absolute precision and control appear to be the ultimate goals of genetic engineering. Precision genome editing in plants has been developed through various approaches, including oligonucleotide-directed mutagenesis (ODM), base editing, prime editing and especially homologous recombination (HR)-based gene targeting. With the advent of CRISPR/Cas for the targeted generation of DNA breaks (single-stranded breaks (SSBs) or double-stranded breaks (DSBs)), a substantial advancement in HR-mediated precise editing frequencies has been achieved. Nonetheless, further research needs to be performed for commercially viable applications of precise genome editing; hence, an alternative innovative method for genome editing may be required. Within this scope, we summarize recent progress regarding precision genome editing mediated by microhomology-mediated end joining (MMEJ) and discuss their potential applications in crop improvement.


Assuntos
Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Edição de Genes , Sistemas CRISPR-Cas/genética , Quebras de DNA de Cadeia Dupla , Reparo do DNA por Junção de Extremidades , Marcação de Genes , Recombinação Homóloga
3.
Plant Cell Rep ; 40(6): 999-1011, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33074435

RESUMO

KEY MESSAGE: CRISPR/Cas9-based multiplexed editing of SlHyPRP1 resulted in precise deletions of its functional motif(s), thereby resulting in salt stress-tolerant events in cultivated tomato. Crop genetic improvement to address environmental stresses for sustainable food production has been in high demand, especially given the current situation of global climate changes and reduction of the global food production rate/population rate. Recently, the emerging clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas)-based targeted mutagenesis has provided a revolutionary approach to crop improvement. The major application of CRISPR/Cas in plant genome editing has been the generation of indel mutations via error-prone nonhomologous end joining (NHEJ) repair of DNA DSBs. In this study, we examined the power of the CRISPR/Cas9-based novel approach in the precise manipulation of protein domains of tomato hybrid proline-rich protein 1 (HyPRP1), which is a negative regulator of salt stress responses. We revealed that the precise elimination of SlHyPRP1 negative-response domain(s) led to high salinity tolerance at the germination and vegetative stages in our experimental conditions. CRISPR/Cas9-based domain editing may be an efficient tool to engineer multidomain proteins of important food crops to cope with global climate changes for sustainable agriculture and future food security.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes/métodos , Proteínas de Plantas/genética , Estresse Salino/fisiologia , Solanum lycopersicum/genética , Agrobacterium tumefaciens/genética , Alelos , Clonagem Molecular , Produtos Agrícolas/genética , Regulação da Expressão Gênica de Plantas , Genoma de Planta , Germinação/genética , Solanum lycopersicum/fisiologia , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/fisiologia , Domínios Proteicos , RNA Guia de Cinetoplastídeos , Estresse Salino/genética , Transformação Bacteriana
4.
Plant Biotechnol J ; 18(10): 2133-2143, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32176419

RESUMO

Genome editing via the homology-directed repair (HDR) pathway in somatic plant cells is very inefficient compared with error-prone repair by nonhomologous end joining (NHEJ). Here, we increased HDR-based genome editing efficiency approximately threefold compared with a Cas9-based single-replicon system via the use of de novo multi-replicon systems equipped with CRISPR/LbCpf1 in tomato and obtained replicon-free but stable HDR alleles. The efficiency of CRISPR/LbCpf1-based HDR was significantly modulated by physical culture conditions such as temperature and light. Ten days of incubation at 31 °C under a light/dark cycle after Agrobacterium-mediated transformation resulted in the best performance among the tested conditions. Furthermore, we developed our single-replicon system into a multi-replicon system that effectively increased HDR efficiency. Although this approach is still challenging, we showed the feasibility of HDR-based genome editing of a salt-tolerant SlHKT1;2 allele without genomic integration of antibiotic markers or any phenotypic selection. Self-pollinated offspring plants carrying the HKT1;2 HDR allele showed stable inheritance and germination tolerance in the presence of 100 mm NaCl. Our work may pave the way for transgene-free editing of alleles of interest in asexually and sexually reproducing plants.

5.
J Public Health Manag Pract ; 24 Suppl 2: S9-S18, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29369252

RESUMO

BACKGROUND: Global progress in reducing maternal mortality requires improving access to maternal and child health services for the most vulnerable groups. This article reports results of implementation research that aimed to increase the acceptability of village-based ethnic minority midwives (EMMs) by local communities in Vietnam through implementing an integrated interventions package. METHODS: The study was carried out in 2 provinces in Vietnam, Dien Bien and Kon Tum. A quasi-experimental survey with pretest/posttest design was adopted, which included 6 months of intervention implementation. The interventions package included introductory "launch" meetings, monthly review meetings at community health centers, and 5-day refresher training for EMMs. A mixed-methods approach was used involving both quantitative and qualitative data. A structured questionnaire was used in the pre- and posttest surveys, complemented by in-depth interviews and focus group discussions with EMMs, relatives of pregnant women, community representatives, and health managers. RESULTS: Introductions of EMMs to their local communities by local authorities and supervision of performance of EMMs contributed to significant increases in utilization of services provided by EMMs, from 58.6% to 87.7%. Key facilitators included information on how to contact EMMs, awareness of services provided by EMMs, and trust in services provided by EMMs. The main barriers to utilization of EMM services, which may affect sustainability of the EMM scheme, were low self-esteem of EMMs and small allowances to EMMs, which also affected the recognition of EMMs in the community. CONCLUSIONS: Providing continuous support and integration of EMMs within frontline service provision and ensuring adequate local budget for monthly allowances are the key factors that should allow sustainability of the EMM scheme and continued improvement of access to maternal and child health care among poor ethnic minority people living in mountainous areas in Vietnam.


Assuntos
Tocologia/estatística & dados numéricos , Saúde das Minorias/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Adulto , Etnicidade/estatística & dados numéricos , Feminino , Grupos Focais/métodos , Humanos , Saúde das Minorias/etnologia , Aceitação pelo Paciente de Cuidados de Saúde/etnologia , Gravidez , Pesquisa Qualitativa , População Rural/estatística & dados numéricos , Inquéritos e Questionários , Vietnã
6.
J Public Health Manag Pract ; 24 Suppl 2: S19-S27, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29369253

RESUMO

BACKGROUND: Gender inequalities influence the utilization of maternal health services in Vietnam, but little research has been published. This study, therefore, aimed to explore the association between gender inequalities and women's utilization of maternal health services in Vietnam. METHODS: The study was conducted in 8 provinces in the South Central Coast region of Vietnam during August 2013 to May 2014. A total of 907 women who delivered a year prior to the date of interview participated in the study. A multiple logistic regression model was used to examine the association between gender inequalities (including sociodemographic determinants of health) and utilization of 4 or more antenatal care (ANC4+) services, institutional delivery, and ever used contraceptive methods. RESULTS: The utilization rate of maternal health services was varied, from 53.9% for ANC4+ to 87.7% for ever used a contraceptive method and 97% for institutional delivery. Ethnicity was identified as the most influential variable out of all sociodemographic determinants of health. Regarding gender inequalities, couple communication was the only variable having significant association with women's utilization of maternal health services. CONCLUSION: Women's equal role within context of their daily life and relations with their husbands (discussing maternal care with husband and having equal income to husband) supported their use of maternal health services. Therefore, there should be concerted efforts from all relevant stakeholders including the health system to focus on disadvantaged women in planning and delivery of maternal health services, especially to ethnic minority women. Male involvement strategy should be implemented to promote maternal health care, especially during the prenatal and postpartum period. To provide more culturally sensitive and right-based approaches in delivery of maternal health services to disadvantaged women in Vietnam, interventions are recommended that promote male involvement, that is, to engage men in service delivery to adapt and ensure the most appropriate and effective maternal health care.


Assuntos
Serviços de Saúde Materna/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Sexismo/tendências , Adolescente , Adulto , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Gravidez , Inquéritos e Questionários , Vietnã
7.
Medicine (Baltimore) ; 103(17): e38000, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38669370

RESUMO

This study aimed to assess the clinical utility of blood lactate-to-bicarbonate (L/B) ratio, as a prognostic factor for 28-day in-hospital mortality in children with dengue shock syndrome (DSS), admitted to the pediatric intensive care unit (PICU). This single-center retrospective study was conducted at a tertiary children hospital in southern Vietnam from 2013 to mid-2022. Prognostic models for DSS mortality were developed, using a predefined set of covariates in the first 24 hours of PICU admission. Area under the curves (AUCs), multivariable logistic and Least Absolute Shrinkage and Selection Operator (LASSO) regressions, bootstrapping and calibration slope were performed. A total of 492 children with DSS and complete clinical and biomarker data were included in the analysis, and 26 (5.3%) patients died. The predictive values for DSS mortality, regarding lactate showing AUC 0.876 (95% CI, 0.807-0.944), and that of L/B ratio 0.867 (95% CI, 0.80-0.934) (P values of both biomarkers < .001). The optimal cutoff point of the L/B ratio was 0.25, while that of lactate was 4.2 mmol/L. The multivariable model showed significant clinical predictors of DSS fatality including severe bleeding, cumulative amount of fluid infused and vasoactive-inotropic score (>30) in the first 24 hours of PICU admission. Combined with the identified clinical predictors, the L/B ratio yielded higher prognostic values (odds ratio [OR] = 8.66, 95% confidence interval [CI], 1.96-38.3; P < .01) than the lactate-based model (OR = 1.35, 95% CI, 1.15-1.58; P < .001). Both the L/B and lactate models showed similarly good performances. Considering that the L/B ratio has a better prognostic value than the lactate model, it may be considered a potential prognostic biomarker in clinical use for predicting 28-day mortality in PICU-admitted children with DSS.


Assuntos
Bicarbonatos , Biomarcadores , Mortalidade Hospitalar , Unidades de Terapia Intensiva Pediátrica , Ácido Láctico , Dengue Grave , Humanos , Masculino , Feminino , Estudos Retrospectivos , Prognóstico , Ácido Láctico/sangue , Dengue Grave/sangue , Dengue Grave/mortalidade , Dengue Grave/diagnóstico , Criança , Pré-Escolar , Biomarcadores/sangue , Bicarbonatos/sangue , Unidades de Terapia Intensiva Pediátrica/estatística & dados numéricos , Vietnã/epidemiologia , Valor Preditivo dos Testes , Lactente , Área Sob a Curva
8.
Nat Commun ; 15(1): 5837, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38992034

RESUMO

To inform clinical trial design and real-world precision pediatric oncology practice, we classified diagnoses, assessed the landscape of mutations, and identified genomic variants matching trials in a large unselected institutional cohort of solid tumors patients sequenced at Dana-Farber / Boston Children's Cancer and Blood Disorders Center. Tumors were sequenced with OncoPanel, a targeted next-generation DNA sequencing panel. Diagnoses were classified according to the International Classification of Diseases for Oncology (ICD-O-3.2). Over 6.5 years, 888 pediatric cancer patients with 95 distinct diagnoses had successful tumor sequencing. Overall, 33% (n = 289/888) of patients had at least 1 variant matching a precision oncology trial protocol, and 14% (41/289) were treated with molecularly targeted therapy. This study highlights opportunities to use genomic data from hospital-based sequencing performed either for research or clinical care to inform ongoing and future precision oncology clinical trials. Furthermore, the study results emphasize the importance of data sharing to define the genomic landscape and targeted treatment opportunities for the large group of rare pediatric cancers we encounter in clinical practice.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Disseminação de Informação , Neoplasias , Medicina de Precisão , Humanos , Neoplasias/genética , Neoplasias/tratamento farmacológico , Criança , Medicina de Precisão/métodos , Masculino , Pré-Escolar , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Adolescente , Lactente , Mutação , Ensaios Clínicos como Assunto , Terapia de Alvo Molecular/métodos , Genômica/métodos , Recém-Nascido
9.
Eur J Dev Res ; 35(1): 196-218, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35221545

RESUMO

Given the increasing importance of green bond as the main funding source for the Sustainable Development Goals, the green bond is an emerging concept in the region of Southeast Asia. In addition, the concurrent Covid-19 pandemic has caused disruption to the development of green bond around the world. This research explores the current development status of the green bond in Southeast Asian countries. A total of thirty-two semi-structured interviews were held with capital market participants in Southeast Asian countries. The results highlight barriers, opportunities, and regulation difficulties, and expected growth for the development of the green bond market. This research is concluded by indicating several propositions that can be tested in the future to generalize the findings from this work. We thus extend the knowledge of green bond in the financial markets of Southeast Asian countries, which also delivers implications for practitioners and policy-makers regarding the development of green bond in Southeast Asian countries.


Compte tenu de l'importance croissante de l'obligation verte en tant que principal attribut financier des objectifs de développement durable (ODD), l'obligation verte est un concept émergent dans la région de l'Asie du Sud-Est. En outre, la pandémie concomitante de Covid-19 a perturbé le développement des obligations vertes dans le monde. Cette étude explore l'état actuel du développement de l'obligation verte dans les pays d'Asie du Sud-Est. Au total, trente-deux entretiens semi-directifs ont été menés avec des acteurs du marché des capitaux dans les pays d'Asie du Sud-Est. Les résultats mettent en évidence les obstacles, les opportunités et les difficultés de réglementation, ainsi que la croissance attendue pour le développement du marché des obligations vertes. Dans sa conclusion, cette étude émet plusieurs propositions qui peuvent être testées à l'avenir pour généraliser les résultats de ce travail. Nous étoffons ainsi la connaissance concernant les obligations vertes sur les marchés financiers des pays d'Asie du Sud-Est, ce qui comporte également des implications pour les praticien·ne·s et les décisionnaires en ce qui concerne le développement des obligations vertes dans les pays d'Asie du Sud-Est.

10.
PLoS One ; 18(12): e0279691, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38085730

RESUMO

INTRODUCTION: Breastfeeding has many benefits for mothers, children, and the environment over both the short and longr-term. Prenatal intention to breastfeed is a powerful predictor of short-term breastfeeding outcomes. OBJECTIVE: This study aims to analyze breastfeeding intentions, including the intention to feed infants with breastmilk only and to continue exclusive breastfeeding to 6 months among pregnant mothers in Hanoi, Vietnam. METHODS: The analysis included 1230 singleton mothers, between 24- and 36-weeks' gestation, who attended antenatal clinics in two hospitals in Hanoi in 2020. RESULTS: The proportion of mothers with an "breastfeeding intention" (i.e., intention to feed an infant with breastmilk only) and "exclusive breastfeeding intention" to 6 months was 59.9% and 41.7%, respectively. Mothers who were 25 years or older (aOR = 1.35, 95%CI:1.00-1.81), had an undergraduate educational degree or higher (aOR = 1.38, 95%CI: 1.08-1.76), had observed another woman breastfeeding (aOR = 1.43, 95%CI: 1.03-2.00), were not living with parents-in-law (aOR = 1.34, CI: 1.05-1.70), and were multiparous (aOR = 1.60, 95%CI: 1.16-2.19) had higher odds of "exclusive breastfeeding intention" to 6 months. Among primiparous women, those who thought their husbands support breastfeeding were more likely to intend to feed an infant with breastmilk only. Among multiparous women, feeding the previous child with breastmilk exclusively before the introduction of complementary foods and not giving solid foods together with water until 6 months, were significant predictors for both breastfeeding intentions. CONCLUSION: Mothers without exclusive breastfeeding experience should be provided with greater support to promote exclusive breastfeeding intention and outcomes.


Assuntos
Aleitamento Materno , Intenção , Lactente , Criança , Feminino , Gravidez , Humanos , Estudos Transversais , Vietnã , Mães , Vitaminas
11.
JCO Precis Oncol ; 7: e2200334, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36996377

RESUMO

PURPOSE: Osteosarcoma risk stratification, on the basis of the presence of metastatic disease at diagnosis and histologic response to chemotherapy, has remained unchanged for four decades, does not include genomic features, and has not facilitated treatment advances. We report on the genomic features of advanced osteosarcoma and provide evidence that genomic alterations can be used for risk stratification. MATERIALS AND METHODS: In a primary analytic patient cohort, 113 tumor and 69 normal samples from 92 patients with high-grade osteosarcoma were sequenced with OncoPanel, a targeted next-generation sequencing assay. In this primary cohort, we assessed the genomic landscape of advanced disease and evaluated the correlation between recurrent genomic events and outcome. We assessed whether prognostic associations identified in the primary cohort were maintained in a validation cohort of 86 patients with localized osteosarcoma tested with MSK-IMPACT. RESULTS: In the primary cohort, 3-year overall survival (OS) was 65%. Metastatic disease, present in 33% of patients at diagnosis, was associated with poor OS (P = .04). The most frequently altered genes in the primary cohort were TP53, RB1, MYC, CCNE1, CCND3, CDKN2A/B, and ATRX. Mutational signature 3 was present in 28% of samples. MYC amplification was associated with a worse 3-year OS in both the primary cohort (P = .015) and the validation cohort (P = .012). CONCLUSION: The most frequently occurring genomic events in advanced osteosarcoma were similar to those described in prior reports. MYC amplification, detected with clinical targeted next-generation sequencing panel tests, is associated with poorer outcomes in two independent cohorts.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Humanos , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Mutação , Osteossarcoma/diagnóstico , Osteossarcoma/genética , Osteossarcoma/patologia , Prognóstico , Amplificação de Genes
12.
Medicine (Baltimore) ; 102(46): e36054, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37986332

RESUMO

Dengue-associated complications, including dengue shock syndrome, severe respiratory distress, and pediatric acute liver failure (PALF), are associated with high mortality rates in patients with dengue. There is increasing prevalence of overweight and obesity among children worldwide. Obesity may activate inflammatory mediators, leading to increased capillary permeability and plasma leakage in patients with dengue. Several studies have shown a correlation between obesity and DSS, but did not include dengue fatality or PALF. Therefore, we hypothesized possible associations between obesity and critical dengue-associated clinical outcomes among PICU-admitted children with DSS, including dengue-related mortality, mechanical ventilation (MV) requirements, and dengue-associated PALF. The nutritional status of the participants was assessed using World Health Organization growth charts. A total of 858 participants with complete nutritional data were enrolled in this study. Obesity was significantly associated with risk of severe respiratory failure and MV support (odds ratio = 2.3, 95% CI: 1.31-4.06, P < .01); however, it was not associated with dengue-associated mortality or acute liver failure. Obese pediatric patients with DSS should be closely monitored for severe respiratory distress and the need for high-flow oxygenation support, particularly MV, soon after hospitalization.


Assuntos
Síndrome do Desconforto Respiratório , Dengue Grave , Humanos , Criança , Respiração Artificial , Dengue Grave/complicações , Dengue Grave/terapia , Obesidade/complicações , Obesidade/epidemiologia , Estado Nutricional , Dispneia/complicações , Síndrome do Desconforto Respiratório/terapia , Síndrome do Desconforto Respiratório/complicações
13.
Nat Med ; 28(8): 1581-1589, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35739269

RESUMO

To evaluate the clinical impact of molecular tumor profiling (MTP) with targeted sequencing panel tests, pediatric patients with extracranial solid tumors were enrolled in a prospective observational cohort study at 12 institutions. In the 345-patient analytical population, median age at diagnosis was 12 years (range 0-27.5); 298 patients (86%) had 1 or more alterations with potential for impact on care. Genomic alterations with diagnostic, prognostic or therapeutic significance were present in 61, 16 and 65% of patients, respectively. After return of the results, impact on care included 17 patients with a clarified diagnostic classification and 240 patients with an MTP result that could be used to select molecularly targeted therapy matched to identified alterations (MTT). Of the 29 patients who received MTT, 24% had an objective response or experienced durable clinical benefit; all but 1 of these patients received targeted therapy matched to a gene fusion. Of the diagnostic variants identified in 209 patients, 77% were gene fusions. MTP with targeted panel tests that includes fusion detection has a substantial clinical impact for young patients with solid tumors.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Neoplasias , Adolescente , Adulto , Biomarcadores Tumorais/genética , Criança , Pré-Escolar , Genômica , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Lactente , Recém-Nascido , Terapia de Alvo Molecular/métodos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/patologia , Estudos Prospectivos , Adulto Jovem
14.
Front Plant Sci ; 12: 722552, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34447405

RESUMO

Plant gene targeting (GT) can be utilized to precisely replace up to several kilobases of a plant genome. Recent studies using the powerful clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) nucleases significantly improved plant GT efficiency. However, GT for loci without associated selection markers is still inefficient. We previously utilized Lachnospiraceae bacterium Cas12a (LbCas12a) in combination with a replicon for tomato GT and obtained high GT efficiency with some selection markers. In this study, we advance our GT system by inhibiting the cNHEJ pathway with small chemical molecules such as NU7441. Further optimization of the GT is also possible with the treatment of silver nitrate possibly via its pronounced actions in ethylene inhibition and polyamine production. Importantly, the GT efficiency is significantly enhanced with the use of a temperature-tolerant LbCas12a (ttLbCas12a) that is capable of performing target cleavage even at low temperatures. Targeted deep sequencing, as well as conventional methods, are used for the assessment of the editing efficiency at both cell and plant levels. Our work demonstrates the significance of the selection of gene scissors, the appropriate design and number of LbCas12a crRNAs, the use of chemical treatments, and the establishment of favorable experimental conditions for further enhancement of plant HDR to enable efficient GT in tomato.

15.
Clin Cancer Res ; 26(12): 2882-2890, 2020 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-32122923

RESUMO

PURPOSE: Several aggressive pediatric cancers harbor alterations in SMARCB1, including rhabdoid tumors, epithelioid sarcoma, and chordoma. As tumor profiling has become more routine in clinical care, we investigated the relationship between SMARCB1 genetic variants identified by next-generation sequencing (NGS) and INI1 protein expression. Therapeutic approaches for INI1-deficient tumors are limited. Early reports suggest a potential role for immune checkpoint inhibition in these patients. Thus, we also investigated PD-L1 and CD8 expression in INI1-negative pediatric brain and solid tumors. EXPERIMENTAL DESIGN: We performed immunohistochemistry (IHC) for INI1 and immune markers (PD-L1, CD8, and CD163) and NGS on tumor samples from 43 pediatric patients who had tumors with INI1 loss on previous IHC or SMARCB1 genomic alterations on prior somatic sequencing. RESULTS: SMARCB1 two-copy deletions and inactivating mutations on NGS were associated with loss of INI1 protein expression. Single-copy deletion of SMARCB1 was not predictive of INI1 loss in tumor histologies not known to be INI1-deficient. In the 27 cases with INI1 loss and successful tumor sequencing, 24 (89%) had a SMARCB1 alteration detected. In addition, 47% (14/30) of the patients with INI1-negative tumors had a tumor specimen that was PD-L1 positive and 60% (18/30) had positive or rare CD8 staining. We report on 3 patients with INI1-negative tumors with evidence of disease control on immune checkpoint inhibitors. CONCLUSIONS: A significant proportion of the INI1-negative tumors express PD-L1, and PD-L1 positivity was associated with extracranial tumor site. These results suggest that clinical trials of immune checkpoint inhibitors are warranted in INI1-negative pediatric cancers.


Assuntos
Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/genética , Inibidores de Checkpoint Imunológico/uso terapêutico , Mutação , Neoplasias/patologia , Proteína SMARCB1/deficiência , Adolescente , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/genética , Criança , Pré-Escolar , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Masculino , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/imunologia , Prognóstico , Proteína SMARCB1/genética
16.
Rice (N Y) ; 12(1): 95, 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31858277

RESUMO

Continuing crop domestication/redomestication and modification is a key determinant of the adaptation and fulfillment of the food requirements of an exploding global population under increasingly challenging conditions such as climate change and the reduction in arable lands. Monocotyledonous crops are not only responsible for approximately 70% of total global crop production, indicating their important roles in human life, but also the first crops to be challenged with the abovementioned hurdles; hence, monocot crops should be the first to be engineered and/or de novo domesticated/redomesticated. A long time has passed since the first green revolution; the world is again facing the challenge of feeding a predicted 9.7 billion people in 2050, since the decline in world hunger was reversed in 2015. One of the major lessons learned from the first green revolution is the importance of novel and advanced trait-carrying crop varieties that are ideally adapted to new agricultural practices. New plant breeding techniques (NPBTs), such as genome editing, could help us succeed in this mission to create novel and advanced crops. Considering the importance of NPBTs in crop genetic improvement, we attempt to summarize and discuss the latest progress with major approaches, such as site-directed mutagenesis using molecular scissors, base editors and especially homology-directed gene targeting (HGT), a very challenging but potentially highly precise genome modification approach in plants. We therefore suggest potential approaches for the improvement of practical HGT, focusing on monocots, and discuss a potential approach for the regulation of genome-edited products.

17.
Int J Public Health ; 62(Suppl 1): 35-40, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27878609

RESUMO

OBJECTIVES: This study aimed at understanding the patterns of the utilization of prenatal diagnostic (PND) services among pregnant women, their satisfaction and its associated factors at three regional prenatal diagnostic centres in Viet Nam. METHODS: A cross-sectional design was used, with a consecutive sampling method to recruit pregnant women who used PND services at the three biggest regional PND services centres in Viet Nam between January and June, 2014. A total of 298 participants, about 100 participants per centre were interviewed and included in data analysis. Descriptive analyses and logistic regression methods were applied to identify association between satisfaction of women and their socio-economic characteristics. RESULTS: 80% of pregnant women received counselling on PND services, whilst 90% received ultrasonography services; 65.4% were satisfied with the PND services they used. Pregnant women, who were in a lower income group and received counselling but did not receive ultrasonography, were more likely to have higher satisfaction levels of PND services. CONCLUSIONS: A process to ensure that every pregnant woman receives sufficient PND counselling before and after receiving PND testing must be given careful and thorough consideration.


Assuntos
Serviços de Diagnóstico/estatística & dados numéricos , Satisfação do Paciente/estatística & dados numéricos , Diagnóstico Pré-Natal/normas , Adulto , Aconselhamento/estatística & dados numéricos , Estudos Transversais , Feminino , Humanos , Gravidez , Diagnóstico Pré-Natal/estatística & dados numéricos , Classe Social , Inquéritos e Questionários , Ultrassonografia/estatística & dados numéricos , Vietnã
18.
Int J Womens Health ; 8: 571-580, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27799825

RESUMO

INTRODUCTION: Since 2011, the Vietnam's Ministry of Health implemented the ethnic minority midwives (EMMs) scheme in order to increase the utilization of maternal health services by women from ethnic minorities and those living in hard-to-reach mountainous areas. This paper analyzes the utilization of antenatal, delivery, and postpartum care provided by EMMs and reports the key determinants of utilization of EMM services as perceived by service users. METHODS: A structured questionnaire was administered in 2015 to all mothers (n=320) who gave birth to a live-born during a 1-year period in 31 villages which had EMM in two provinces, Dien Bien and Kon Tum. A multivariate logistic regression model was used to examine the association between all potential factors and the use of services provided by EMMs. RESULTS: We found that EMMs provided more antenatal care and postnatal care as compared with delivery services, which corresponded to their job descriptions. The results also showed that utilization of antenatal care provided by EMMs was lower than that of postnatal care. The proportion of those who never heard about EMM was high (24%). Among the mothers who knew about EMM services, 33.4% had antenatal checkups, 20.1% were attended during home deliveries, and 57.3% had postnatal visits by an EMM. Key factors that determined the use of EMM services included knowledge of the location of EMM's house, being aware about EMMs by health workers, trust in services provided by EMMs, and perception that many others mothers in a village also knew about EMM services. CONCLUSION: EMM seems to be an important mechanism to ensure assistance during home births and postnatal care for ethnic minority groups, who are often resistant to attend health facilities. Building trust and engaging with communities are the key facilitators to increase the utilization of services provided by EMMs. Communication campaigns to raise awareness about EMMs and to promote their services in the village, particularly by other health workers, represent an important strategy to further improve effectiveness of EMM scheme.

19.
BMC Proc ; 5 Suppl 2: S6, 2011 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-21554764

RESUMO

BACKGROUND: Genetic disease studies investigate relationships between changes in chromosomes and genetic diseases. Single haplotypes provide useful information for these studies but extracting single haplotypes directly by biochemical methods is expensive. A computational method to infer haplotypes from genotype data is therefore important. We investigate the problem of computing the minimum number of recombination events for general pedigrees with two sites for all members. RESULTS: We show that this NP-hard problem can be parametrically reduced to the Bipartization by Edge Removal problem and therefore can be solved by an O(2k · n2) exact algorithm, where n is the number of members and k is the number of recombination events. CONCLUSIONS: Our work can therefore be useful for genetic disease studies to track down how changes in haplotypes such as recombinations relate to genetic disease.

20.
Algorithms Mol Biol ; 6: 8, 2011 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-21504601

RESUMO

BACKGROUND: Genetic disease studies investigate relationships between changes in chromosomes and genetic diseases. Single haplotypes provide useful information for these studies but extracting single haplotypes directly by biochemical methods is expensive. A computational method to infer haplotypes from genotype data is therefore important. We investigate the problem of computing the minimum number of recombination events for general pedigrees with a small number of sites for all members. RESULTS: We show that this NP-hard problem can be parametrically reduced to the Bipartization by Edge Removal problem with additional parity constraints. We solve this problem with an exact algorithm that runs in time, where n is the number of members, m is the number of sites, and k is the number of recombination events. CONCLUSIONS: This algorithm infers haplotypes for a small number of sites, which can be useful for genetic disease studies to track down how changes in haplotypes such as recombinations relate to genetic disease.

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