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1.
Hemoglobin ; 48(1): 60-62, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38314576

RESUMO

Patients with the genotype of ß0/ß0 for ß-thalassemia (ß-thal) usually behave as ß-thal major (ß-TM) phenotype which is transfusion-dependent. The pathophysiology of ß-thal is the imbalance between α/ß-globin chains. The degree of α/ß-globin imbalance can be reduced by the more effective synthesis of γ-globin chains, and increased Hb F levels, modifying clinical severity of ß-TM. We report a Chinese child who had homozygous ß0-thal and a heterozygous KLF1 mutation. The patient had a moderate anemia since 6 months old, keeping a baseline Hb value of 8.0-9.0 g/dL. She had normal development except for a short stature (3rd percentile) until 6 years old, when splenomegaly and facial bone deformities occurred. Although genetic alteration of KLF1 expression in ß0/ß0 patients can result in some degree of disease alleviation, our case shows that it is insufficient to ameliorate satisfactorily the presentation. This point should be borne in mind for physicians who provide the genetic counseling and prenatal diagnosis to at-risk families.


Assuntos
Globinas beta , Talassemia beta , Criança , Feminino , Humanos , Lactente , alfa-Globinas/genética , Globinas beta/genética , Talassemia beta/genética , China , Seguimentos , Genótipo , Mutação
2.
Sex Health ; 20(4): 315-322, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37121601

RESUMO

BACKGROUND: Factory workers are a key population for HIV transmission in China, as they often engage in sexual risk behaviours. This study aims to evaluate sexual risk behaviours and associated factors among factory workers in Shenzhen, China. METHODS: A cross-sectional study was conducted by using multi-stage stratified cluster random sampling. Full-time workers aged ≥18years were eligible to participate in the study. A self-administered questionnaire was used to collect information. Univariate and multivariable logistic regression were applied to assess factors associated with sexual risk behaviours. RESULTS: A total of 2029 factory workers were included. Mean age was 37.2 (±4.4)years; 48.5% were men. Two-thirds (64.9%) had had vaginal intercourse. Their sexual risk behaviours included condomless sex with casual partners in the last sex episode (23.6%), multiple sex partners (11.5%) and engaging in commercial sex (8.4%), in the past year. Having HIV/AIDS knowledge (adjusted odds ratio (AOR) 0.41, 95% confidence interval (CI) 0.24-0.70) and using a condom at sexual debut (AOR 0.08, 95% CI 0.05-0.13) were factors associated with condomless sex with casual partners in the last sex episode. Males (AOR 3.03, 95% CI 1.96-4.69 and AOR 2.19, 95% CI 1.33-3.60), local workers (AOR 2.11, 95% CI 1.01-4.42 and AOR 3.42, 95% CI 1.63-7.21), being single (AOR 2.04, 95% CI 1.39-3.01 and AOR 2.49, 95% CI 1.61-3.87), having sexual debut aged Conclusions : Sexual risk behaviours were prevalent despite most participants having basic HIV/AIDS knowledge. Future workplace-based prevention programs should target factory workers and there should be a focus on enhanced sexual education to reduce HIV transmission in China.


Assuntos
Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Masculino , Feminino , Humanos , Adulto , Trabalho Sexual , Estudos Transversais , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Comportamento Sexual , Parceiros Sexuais , Preservativos , Assunção de Riscos , China/epidemiologia
3.
Comput Ind Eng ; 179: 109158, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36960126

RESUMO

The outbreak of the Coronavirus Disease 2019 (COVID-19) has put the resilience of a country's healthcare infrastructure to the most severe test. The challenge of taking emergency measures to optimize the supply of medical resources and effectively meet the medical needs of residents is an important issue that needs to be resolved urgently in the prevention and control of public health emergencies. This paper analyzes cascading failures and optimization of the resilience of the hospital infrastructure system (HIS) with the presence of the COVID-19. It proposes a propagation model to describe the COVID-19 infectious process and establishes a cascading failure model of a HIS to analyze its failure mechanism. It also proposes a method for optimizing the resilience of HIS. Then the supplies and demands in maintaining the operations of HIS are studied, and a restoration strategy is obtained. Finally, simulation analysis of the spread of the COVID-19 is carried out to illustrate the applicability of the proposed method.

4.
Hemoglobin ; 46(2): 129-131, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35950878

RESUMO

We report a new hemoglobin (Hb) variant that we have named Hb Wanjiang (HBB: c.255_264delinsTTTTTCTCAG). We identified this variant in a Chinese man by the next-generation sequencing (NGS) method. The father of the proband also carried the same variant. This variant results from a 10 bp deletion at codons 84-87 of the ß-globin chain, replaced with 10 nucleotides coming from the δ-globin gene at the same position, leading to the substitution of two amino acids in the peptide chain with no change in the ß-globin chain length. The heterozygotes had a normal hematological feature with no abnormal Hb variant detectable on capillary electrophoresis (CE) and high performance liquid chromatography (HPLC). The combination of Hb Wanjiang and ß-thalassemia (ß-thal) was not found to aggravate anemia.


Assuntos
Hemoglobinas Anormais , Globinas delta , Substituição de Aminoácidos , Aminoácidos , Códon , Hemoglobinas Anormais/genética , Humanos , Masculino , Nucleotídeos , Globinas beta/química , Globinas beta/genética , Globinas delta/genética
5.
Front Psychol ; 13: 837996, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35391955

RESUMO

Factory workers make up a large proportion of China's internal migrants and may be highly susceptible to job and adaptation stress, negative affective states (e.g., depression and anxiety), and Internet gaming disorder (IGD). This cross-sectional study investigated the relationships between job stress, psychological adaptation, negative affective states and IGD among 1,805 factory workers recruited by stratified multi-stage sampling between October and December 2019. Structural equation modeling (SEM) was conducted to test the proposed mediation model. Among the participants, 67.3% were male and 71.7% were aged 35 years old or below. The prevalence of probable depression, probable anxiety, and IGD was 39.3, 28.7, and 7.5%. Being male, younger age, and shorter duration of living in Shenzhen were associated with higher IGD scores. Job stress was significantly associated with IGD (ß = 0.11, p = 0.01) but not with negative affective states (ß = 0.01, p = 0.77). Psychological adaptation was significantly associated with negative affective states (ß = -0.37, p < 0.001) but not with IGD (ß = 0.09, p > 0.05). Negative affective states were positively associated with IGD (ß = 0.27, p < 0.001). The indirect effect of psychological adaptation (ß = -0.10, p = 0.004) but not job stress (ß = 0.003, p = 0.77) on IGD through negative affective states was statistically significant. The observed psychological correlates and mechanisms are modifiable, and can inform the design of evidence-based prevention programs for depression, anxiety, and IGD in this population.

6.
J Mater Chem B ; 10(10): 1571-1581, 2022 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-35147632

RESUMO

The ever-growing antibiotic-resistant bacteria pose a huge threat to public health. Restoring the susceptibility of ineffective antibiotics by inorganic nanomaterials and combining the photothermal and antibiotic effects could be an optional strategy to combat this resistance. Here, cefotaxime (CTX) loaded tellurium nanoparticles (Te NPs) were fabricated to recover the antibacterial activity of the ineffective ß-lactam antibiotic CTX against methicillin-resistant Staphylococcus aureus (MRSA) and at the same time perform photothermal therapy under light-emitting diode (LED) irradiation with a wavelength in the range of 420-480 nm. The combination of 50 µg mL-1 Te-CTX NPs with 5 min LED irradiation produced a 30.4 °C temperature increase and killed 99% of MRSA in vitro. In vivo evaluation in mice revealed that Te-CTX NPs and LED irradiation accelerated the healing of MRSA infected wounds and presented biosafety. Furthermore, this combination accelerated glutathione oxidation and resulted in the disruption of the antioxidant defence system of MRSA. Such a synergistic antibiotic and photothermal therapy provides an innovative way for the treatment of antibiotic-resistant bacterial infections.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Nanocompostos , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Cefotaxima , Sinergismo Farmacológico , Camundongos , Telúrio/farmacologia
7.
Artigo em Inglês | MEDLINE | ID: mdl-35055553

RESUMO

The Paris agreement is a unified arrangement for the global response to climate change and entered into force on 4 November 2016. Its long-term goal is to hold the global average temperature rise well below 2 °C. China is committed to achieving carbon neutrality by 2060 through various measures, one of which is green technology innovation (GTI). This paper aims to analyze the levels of GTI in 30 provinces in mainland China between 2001 and 2019. It uses the spatial econometric models and panel threshold models along with the slack based measure (SBM) and Global Malmquist-Luenberger (GML) index to analyze the spatial spillover and nonlinear effects of GTI on regional carbon emissions. The results show that GTI achieves growth every year, but the innovation efficiency was low. China's total carbon dioxide emissions were increasing at a marginal rate, but the carbon emission intensity was declining year by year. Carbon emissions were spatially correlated and show significant positive agglomeration characteristics. The spatial spillover of GTI plays an important role in reducing carbon dioxide emissions. In the underdeveloped regions in China, this emission reduction effect was even more significant.


Assuntos
Dióxido de Carbono , Invenções , Dióxido de Carbono/análise , China , Desenvolvimento Econômico , Eficiência , Modelos Econométricos
8.
Hemoglobin ; 46(6): 341-343, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36815319

RESUMO

Hb Zürich-Albisrieden, [α59(E8)Gly→Arg, HBA1: c.178G>C] is a rare and highly unstable α-globin chain variant. The involved mutation has been reported in both HBA1 and HBA2 genes. A few compound heterozygotes of Hb Zürich-Albisrieden and α0-thalassemia have shown that this variant is associated with severe Hb H disease. We describe here another case of Hb Zürich-Albisrieden who presented with transfusion-dependent anemia beginning shortly after birth.


Assuntos
Anemia , Hemoglobinas Anormais , Talassemia alfa , Humanos , Hemoglobinas Glicadas , Talassemia alfa/genética , Hemoglobinas Anormais/genética , Mutação , alfa-Globinas/genética
9.
Front Pediatr ; 9: 811812, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35127601

RESUMO

OBJECTIVE: To analyze genetic mutations in a Chinese pedigree affected with Alpha-thalassemia X-linked intellectual disability syndrome, providing a precise diagnosis and genetic counseling. METHODS: Clinical data was collected. A novel alternative splicing variant detected by whole-exome sequencing was validated by Sanger sequencing. The functional effect of the mutation was predicted with Mutation Tasting. The analysis of 5' splice site score was estimated with MaxEntScan. Changes in amino acid sequencing were predicted with Mutalyzer. The tertiary structures of the wild type and mutation-carrying protein were predicted by I-TASSER. RNA was extracted from peripheral blood lymphocytes from the proband, his mother and a healthy control. Quantitative Real-Time PCR was used to detect mRNA expression. RESULTS: The proband presented with severe intellectual disability, developmental delay, characteristic facies, seizures and cryptorchidism. A novel hemizygous duplication mutation in the ATRX gene in a splice site between exons 3 and 4, NM_000489: c.189+1dupG, was identified with WES in the proband. Sanger sequencing confirmed that the mutation was inherited from his mother, who carried a heterozygous mutation, while his father was not affected. Bioinformatics analysis indicated that the splicing region where the mutation was located is highly conserved and the variant was damaging, producing a truncated protein due to the premature translation of a stop codon. Sanger sequencing with the Quantitative Real-Time PCR product containing a G base inserted between bases 189 and 190. The level of mRNA expression showed that ATRX gene transcription decreased due to the mutation (P < 0.05). CONCLUSIONS: A novel mutation in ATRX was found in this pedigree and was confirmed to be pathogenic through functional studies. Our research expanded the spectrum of ATRX gene mutations, providing a precise diagnosis and a basis for genetic counseling.

10.
Biomed J ; 44(6 Suppl 2): S190-S200, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-35292267

RESUMO

BACKGROUND: The immunochemical fecal occult blood test (iFOBT) for colorectal cancer (CRC) screening and the serum carcinoembryonic antigen (CEA) assay for disease detection of CRC is associated with a high false-positive rate and a low detection sensitivity, respectively. There is an unmet need to define additional modalities to complement these assays. Different subsets of circulating tumor cells (CTCs) are present in the peripheral blood of cancer patients. Whether or not CTCs testing supplements these clinical assays and is valuable for patients with CRC was investigated. METHODS: CTCs were enriched from pre-operative patients with CRC (n = 109) and the non-cancerous controls (n = 65). CTCs expressing either epithelial cell adhesion molecule (EpCAM) or podoplanin (PDPN, the marker associated with poor cancer prognosis) were defined by immunofluorescence staining and were analyzed alone or in combination with iFOBT or serum CEA. RESULTS: Patients with early or advanced stage of CRC can be clearly identified and differentiated from the non-cancerous controls (p < 0.001) by EpCAM+-CTC or PDPN+-CTC count. The sensitivity and specificity of EpCAM+-CTCs was 85.3% and 78.5%, respectively, when the cutoff value was 23 EpCAM+-CTCs/mL of blood; and the sensitivity and specificity of PDPN+-CTCs was 78.0% and 75.4%, respectively, when the cutoff value was 7 PDPN+-CTCs/mL of blood. Combined analysis of iFOBT with the EpCAM+-CTC and PDPN+-CTC count reduced the false-positive rate of iFOBT from 56.3% to 18.8% and 23.4%, respectively. Combined analysis of serum CEA with the EpCAM+-CTC and PDPN+-CTC count increased the disease detection rate from 30.3% to 89.9% and 86.2%, respectively. CONCLUSION: CTC testing could supplement iFOBT to improve CRC screening and supplement serum CEA assay for better disease detection of patients with CRC.


Assuntos
Neoplasias Colorretais , Células Neoplásicas Circulantes , Biomarcadores Tumorais , Antígeno Carcinoembrionário , Neoplasias Colorretais/metabolismo , Detecção Precoce de Câncer , Molécula de Adesão da Célula Epitelial , Humanos , Células Neoplásicas Circulantes/patologia
11.
JMIR Mhealth Uhealth ; 8(10): e20847, 2020 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-33118956

RESUMO

BACKGROUND: Associations between higher levels of patient engagement and better health outcomes have been found in face-to-face interventions; studies on such associations with mobile health (mHealth) interventions have been limited and the results are inconclusive. OBJECTIVE: The objective of this study is to investigate the relationship between patient engagement in an mHealth intervention and depressive symptoms using repeated measures of both patient engagement and patient outcomes at 4 time points. METHODS: Data were drawn from a randomized controlled trial (RCT) of an mHealth intervention aimed at reducing depressive symptoms among people living with HIV and elevated depressive symptoms. We examined the association between patient engagement and depressive symptoms in the intervention group (n=150) where participants received an adapted cognitive-behavioral stress management (CBSM) course and physical activity promotion on their WeChat social media app. Depressive symptoms were repeatedly measured using the Patient Health Questionnaire (PHQ-9) at baseline and 1 month, 2 months, and 3 months. Patient engagement was correspondingly measured by the completion rate, frequency of items completed, and time spent on the program at 1 month, 2 months, and 3 months. Latent growth curve models (LGCMs) were used to explore the relationship between patient engagement and depressive symptoms at multiple time points in the intervention. RESULTS: The mean PHQ-9 scores were 10.2 (SD 4.5), 7.7 (SD 4.8), 6.5 (SD 4.7), and 6.7 (SD 4.1) at baseline, 1 month, 2 months, and 3 months, respectively. The mean completion rates were 50.6% (SD 31.8%), 51.5% (SD 32.2%), and 50.8% (SD 33.7%) at 1, 2, and 3 months, respectively; the average frequencies of items completed were 18.0 (SD 14.6), 32.6 (SD 24.8), and 47.5 (SD 37.2) at 1, 2, and 3 months, respectively, and the mean times spent on the program were 32.7 (SD 66.7), 65.4 (SD 120.8), and 96.4 (SD 180.4) minutes at 1, 2, and 3 months, respectively. LGCMs showed good model fit and indicated that a higher completion rate (ß at 3 months=-2.184, P=.048) and a greater frequency of items completed (ß at 3 months=-0.018, P=.04) were associated with fewer depressive symptoms at 3 months. Although not significant, similar trends were found in the abovementioned relationships at 1 and 2 months. There was no significant relationship between time spent on the program and depressive symptoms. CONCLUSIONS: This study revealed a positive association between patient engagement and health outcomes at 3 months of an mHealth intervention using LGCMs and repeated measures data. The results underscore the importance of improving patient engagement in mHealth interventions to improve patient-centered health outcomes. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-IPR-17012606; https://tinyurl.com/yxb64mef. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s12889-018-5693-1.


Assuntos
Infecções por HIV , Telemedicina , Depressão/epidemiologia , Depressão/terapia , Exercício Físico , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Infecções por HIV/terapia , Humanos , Participação do Paciente
12.
J Med Internet Res ; 22(8): e20328, 2020 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-32716899

RESUMO

BACKGROUND: People undergoing mass home- and community-based quarantine are vulnerable to mental health disorders during outbreaks of coronavirus disease (COVID-19), but few studies have evaluated the associated psychosocial factors. OBJECTIVE: This study aimed to estimate the prevalence of anxiety and depressive symptoms and identify associated demographic and psychosocial factors in the general Chinese population during the COVID-19 pandemic quarantine period. METHODS: Participants aged 18 years or above were recruited in a cross-sectional online survey using snowball sampling from February 26-29, 2020. The survey included questions on demographics, family relationships, chronic diseases, quarantine conditions, lifestyle, COVID-19 infection, and anxiety and depressive symptoms. Logistic regression analyses were conducted to identify factors associated with elevated anxiety or depressive symptoms. RESULTS: Out of 2331 participants, 762 (32.7%) experienced elevated anxiety or depressive symptoms. Nine risk factors associated with anxiety or depressive symptoms included younger age, reduced income, having cancer or other chronic diseases, having family members living with cancer, concerns related to COVID-19 infection for themselves or family members, living alone, having family conflicts, having <3 or >8 hours of sedentary time per day, and worsened sleep quality. CONCLUSIONS: The findings highlight an urgent need for psychological support for populations at high risk for elevated anxiety or depressive symptoms during the COVID-19 pandemic.


Assuntos
Ansiedade/epidemiologia , Infecções por Coronavirus/epidemiologia , Depressão/epidemiologia , Surtos de Doenças , Inquéritos Epidemiológicos , Saúde Mental/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Quarentena/psicologia , Adolescente , Adulto , Ansiedade/psicologia , COVID-19 , China/epidemiologia , Estudos Transversais , Depressão/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Fatores de Risco , Adulto Jovem
13.
Sci Rep ; 10(1): 4526, 2020 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-32161294

RESUMO

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers worldwide. While both genetic and environmental factors have been linked to the incidence and mortality associated with CRC, an ethnic aspect of its etiology has also emerged. Since previous large-scale cancer genomics studies are mostly based on samples of European ancestry, the patterns of clinical events and associated mechanisms in other minority ethnic patients suffering from CRC are largely unexplored. We collected 104 paired and adjacent normal tissue and CRC tumor samples from Taiwanese patients and employed an integrated approach - paired expression profiles of mRNAs and microRNAs (miRNAs) combined with transcriptome-wide network analyses - to catalog the molecular signatures of this regional cohort. On the basis of this dataset, which is the largest ever reported for this type of systems analysis, we made the following key discoveries: (1) In comparison to the The Cancer Genome Atlas (TCGA) data, the Taiwanese CRC tumors show similar perturbations in expressed genes but a distinct enrichment in metastasis-associated pathways. (2) Recurrent as well as novel CRC-associated gene fusions were identified based on the sequencing data. (3) Cancer subtype classification using existing tools reveals a comparable distribution of tumor subtypes between Taiwanese cohort and TCGA datasets; however, this similarity in molecular attributes did not translate into the predicted subtype-related clinical outcomes (i.e., death event). (4) To further elucidate the molecular basis of CRC prognosis, we developed a new stratification strategy based on miRNA-mRNA-associated subtyping (MMAS) and consequently showed that repressed WNT signaling activity is associated with poor prognosis in Taiwanese CRC. In summary, our findings of distinct, hitherto unreported biosignatures underscore the heterogeneity of CRC tumorigenesis, support our hypothesis of an ethnic basis of disease, and provide prospects for translational medicine.


Assuntos
Transformação Celular Neoplásica/genética , Neoplasias Colorretais/etiologia , Perfilação da Expressão Gênica , Transcriptoma , Biomarcadores Tumorais , Neoplasias Colorretais/epidemiologia , Biologia Computacional/métodos , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , MicroRNAs/genética , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Interferência de RNA , RNA Mensageiro/genética , Taiwan/epidemiologia
14.
Reliab Eng Syst Saf ; 202: 107037, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34170996

RESUMO

Most of the supply chain literature assumes that product substitution is an effective method to mitigate supply chain disruptions and that all production lines either survive or are disrupted together. Such assumptions, however, may not hold in the real world: (1) when there is a shortfall of all products, product substitution may be inadequate unless it is paired with other strategies such as dual sourcing; and (2) production lines do not survive forever and may fail. To relax such assumptions, this paper therefore investigates the situations that the manufacturer may optimize substitution policy and dual sourcing policy to cope with supply chain disruptions. The paper obtains and compares the optimal policies for both deterministic and stochastic demands. A real-world case is also studied to verify the effectiveness of the proposed model.

15.
Cancer Med ; 8(11): 5116-5127, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31328403

RESUMO

Approximately, 25% of nasopharyngeal carcinoma (NPC) patients develop recurrent disease. NPC may involve relatively few genomic alterations compared to other cancers due to its association with Epstein-Barr virus (EBV). We envisioned that in-depth sequencing of tumor tissues might provide new insights into the genetic alterations of this cancer. Thirty-three NPC paired tumor/adjacent normal or peripheral blood mononuclear cell samples were deep-sequenced (>1000×) with respect to a panel of 409 cancer-related genes. Newly identified mutations and its correlation with clinical outcomes were evaluated. Profiling of somatic mutations and copy number variations (CNV) in NPC tumors identified alterations in RTK/RAS/PI3K, NOTCH, DNA repair, chromatin remodeling, cell cycle, NF-κB, and TGF-ß pathways. In addition, patients harbored CNV among 409 cancer-related genes and missense mutations in TGF-ß/SMAD signaling were associated with poor overall survival and poor recurrence-free survival, respectively. The CNV events were correlated with plasma EBV copies, while mutations in TGFBR2 and SMAD4 abrogate SMAD-dependent TGF-ß signaling. Functional analysis revealed that the new TGFBR2 kinase domain mutants were incapable of transducing the signal, leading to failure of phosphorylation of SMAD2/3 and activation of downstream TGF-ß-mediated cell growth arrest. This study provides evidence supporting CNV and dysregulated TGF-ß signaling contributes to exacerbating the NPC pathogenesis.


Assuntos
Mutação , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Oncogenes , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo , Biomarcadores Tumorais , Variações do Número de Cópias de DNA , Feminino , Expressão Gênica , Perfilação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Ligação Proteica , Receptor do Fator de Crescimento Transformador beta Tipo II/genética , Receptor do Fator de Crescimento Transformador beta Tipo II/metabolismo , Proteína Smad4/genética , Proteína Smad4/metabolismo
16.
BMC Med Genomics ; 12(Suppl 5): 99, 2019 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-31296206

RESUMO

BACKGROUND: CoMut plot is widely used in cancer research publications as a visual summary of mutational landscapes in cancer cohorts. This summary plot can inspect gene mutation rate and sample mutation burden with their relevant clinical details, which is a common first step for analyzing the recurrence and co-occurrence of gene mutations across samples. The cBioPortal and iCoMut are two web-based tools that allow users to create intricate visualizations from pre-loaded TCGA and ICGC data. For custom data analysis, only limited command-line packages are available now, making the production of CoMut plots difficult to achieve, especially for researchers without advanced bioinformatics skills. To address the needs for custom data and TCGA/ICGC data comparison, we have created CoMutPlotter, a web-based tool for the production of publication-quality graphs in an easy-of-use and automatic manner. RESULTS: We introduce a web-based tool named CoMutPlotter to lower the barriers between complex cancer genomic data and researchers, providing intuitive access to mutational profiles from TCGA/ICGC projects as well as custom cohort studies. A wide variety of file formats are supported by CoMutPlotter to translate cancer mutation profiles into biological insights and clinical applications, which include Mutation Annotation Format (MAF), Tab-separated values (TSV) and Variant Call Format (VCF) files. CONCLUSIONS: In summary, CoMutPlotter is the first tool of its kind that supports VCF file, the most widely used file format, as its input material. CoMutPlotter also provides the most-wanted function for comparing mutation patterns between custom cohort and TCGA/ICGC project. Contributions of COSMIC mutational signatures in individual samples are also included in the summary plot, which is a unique feature of our tool. CoMutPlotter is freely available at http://tardis.cgu.edu.tw/comutplotter .


Assuntos
Biologia Computacional/métodos , Internet , Mutação , Neoplasias/genética , Estudos de Coortes , Gráficos por Computador , Humanos
17.
EMBO Rep ; 20(5)2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30948460

RESUMO

Adenosine deaminase acting on RNA (ADAR)-catalyzed adenosine-to-inosine RNA editing is potentially dysregulated in neoplastic progression. However, how this transcriptome recoding process is functionally correlated with tumorigenesis remains largely elusive. Our analyses of RNA editome datasets identify hypoxia-related genes as A-to-I editing targets. In particular, two negative regulators of HIF-1A-the natural antisense transcript HIF1A-AS2 and the ubiquitin ligase scaffold LIMD1-are directly but differentially modulated by ADAR1. We show that HIF1A-AS2 antagonizes the expression of HIF-1A in the immediate-early phase of hypoxic challenge, likely through a convergent transcription competition in cis ADAR1 in turn suppresses transcriptional progression of the antisense gene. In contrast, ADAR1 affects LIMD1 expression post-transcriptionally, by interfering with the cytoplasmic translocation of LIMD1 mRNA and thus protein translation. This multi-tier regulation coordinated by ADAR1 promotes robust and timely accumulation of HIF-1α upon oxygen depletion and reinforces target gene induction and downstream angiogenesis. Our results pinpoint ADAR1-HIF-1α axis as a hitherto unrecognized key regulator in hypoxia.


Assuntos
Adenosina Desaminase/genética , Hipóxia Celular/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Proteínas de Ligação a RNA/genética , Transdução de Sinais/genética , Carcinogênese/genética , Linhagem Celular Tumoral , Citoplasma/genética , Humanos , Proteínas com Domínio LIM/genética , Células MCF-7 , Edição de RNA/genética , RNA Mensageiro/genética , Transcrição Gênica/genética
18.
Environ Int ; 127: 253-266, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30928849

RESUMO

A circular economy relies on demonstrating the quality and environmental safety of wastes that are recovered and reused as products. Policy-level risk assessments, using generalised exposure scenarios, and informed by stakeholder communities have been used to appraise the acceptability of necessary changes to legislation, allowing wastes to be valued, reused and marketed. Through an extensive risk assessment exercise, summarised in this paper, we explore the burden of proof required to offer safety assurance to consumer and brand-sensitive food sectors in light of attempts to declassify, as wastes, quality-assured, source-segregated compost and anaerobic digestate products in the United Kingdom. We report the residual microbiological and chemical risks estimated for both products in land application scenarios and discuss these in the context of an emerging UK bioeconomy worth £52bn per annum. Using plausible worst case assumptions, as demanded by the quality food sector, risk estimates and hazard quotients were estimated to be low or negligible. For example, the human health risk of E. coli 0157 illness from exposure to microbial residuals in quality-assured composts, through a ready-to-eat vegetable consumption exposure route, was estimated at ~10-8 per person per annum. For anaerobic digestion residues, 7 × 10-3cases of E. coli 0157 were estimated per annum, a potential contribution of 0.0007% of total UK cases. Hazard quotients for potential chemical contaminants in both products were insufficient in magnitude to merit detailed quantitative risk assessments. Stakeholder engagement and expert review was also a substantive feature of this study. We conclude that quality-assured, source-segregated products applied to land, under UK quality protocols and waste processing standards, pose negligible risks to human, animal, environmental and crop receptors, providing that risk management controls set within the standards and protocols are adhered to.


Assuntos
Compostagem , Anaerobiose , Animais , Compostagem/economia , Escherichia coli , Humanos , Medição de Risco , Solo/química , Reino Unido
19.
Gigascience ; 7(1): 1-10, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29194536

RESUMO

Background: Despite their lack of protein-coding potential, long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) have emerged as key determinants in gene regulation, acting to fine-tune transcriptional and signaling output. These noncoding RNA transcripts are known to affect expression of messenger RNAs (mRNAs) via epigenetic and post-transcriptional regulation. Given their widespread target spectrum, as well as extensive modes of action, a complete understanding of their biological relevance will depend on integrative analyses of systems data at various levels. Findings: While a handful of publicly available databases have been reported, existing tools do not fully capture, from a network perspective, the functional implications of lncRNAs or circRNAs of interest. Through an integrated and streamlined design, circlncRNAnet aims to broaden the understanding of ncRNA candidates by testing in silico several hypotheses of ncRNA-based functions, on the basis of large-scale RNA-seq data. This web server is implemented with several features that represent advances in the bioinformatics of ncRNAs: (1) a flexible framework that accepts and processes user-defined next-generation sequencing-based expression data; (2) multiple analytic modules that assign and productively assess the regulatory networks of user-selected ncRNAs by cross-referencing extensively curated databases; (3) an all-purpose, information-rich workflow design that is tailored to all types of ncRNAs. Outputs on expression profiles, co-expression networks and pathways, and molecular interactomes, are dynamically and interactively displayed according to user-defined criteria. Conclusions: In short, users may apply circlncRNAnet to obtain, in real time, multiple lines of functionally relevant information on circRNAs/lncRNAs of their interest. In summary, circlncRNAnet provides a "one-stop" resource for in-depth analyses of ncRNA biology. circlncRNAnet is freely available at http://app.cgu.edu.tw/circlnc/.


Assuntos
Epigênese Genética , Redes Reguladoras de Genes , RNA Longo não Codificante/genética , RNA Mensageiro/genética , RNA/genética , Interface Usuário-Computador , Biologia Computacional , Bases de Dados de Ácidos Nucleicos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Internet , MicroRNAs/genética , MicroRNAs/metabolismo , RNA/metabolismo , Processamento Pós-Transcricional do RNA , RNA Circular , RNA Longo não Codificante/metabolismo , RNA Mensageiro/metabolismo , Análise de Sequência de RNA , Transcrição Gênica
20.
Artigo em Inglês | MEDLINE | ID: mdl-29211039

RESUMO

The prevalence of diabetes is steadily increasing in China. When diabetes is uncontrolled, it generates dire consequences for health and well-being. Numerous studies have shown that health outcomes were associated with social support and medication adherence. Previous study confirmed that social support was associated with medication adherence in patients with heart failure, HIV diseases, and first-episode psychosis. However, the relationship between social support and medication adherence in patients with type 2 diabetes mellitus (T2DM) is remains unclear. This study aims to examine whether social support is associated with medication adherence in patients with T2DM. This study was conducted in the First Affiliated Hospital of the General Hospital of the People's Liberation Army (PLA). In Beijing, a systematic random sample of 412 patients with T2DM over 18 years was recruited at baseline, and demographic characteristics, clinical data and their assessment of social support were collected from medical records and self-reported questionnaires. 330 of these patients completed a self-report measure of medication adherence at the sixth month after baseline data collection. Regression analysis showed that social support presented a positive effect on medication adherence, additionally, support utilization and the subscale of social support exhibited a significantly strong influence on medication adherence in patients with T2DM. Although medication adherence was influenced by multiple factors, this finding confirmed that social support must be recognized as a core element in interventions aimed at improving in the management of patients with T2DM.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Adesão à Medicação/estatística & dados numéricos , Apoio Social , Idoso , Povo Asiático , Pequim , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Autorrelato , Inquéritos e Questionários
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