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1.
Nature ; 631(8021): 583-592, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38768635

RESUMEN

Rare coding variants that substantially affect function provide insights into the biology of a gene1-3. However, ascertaining the frequency of such variants requires large sample sizes4-8. Here we present a catalogue of human protein-coding variation, derived from exome sequencing of 983,578 individuals across diverse populations. In total, 23% of the Regeneron Genetics Center Million Exome (RGC-ME) data come from individuals of African, East Asian, Indigenous American, Middle Eastern and South Asian ancestry. The catalogue includes more than 10.4 million missense and 1.1 million predicted loss-of-function (pLOF) variants. We identify individuals with rare biallelic pLOF variants in 4,848 genes, 1,751 of which have not been previously reported. From precise quantitative estimates of selection against heterozygous loss of function (LOF), we identify 3,988 LOF-intolerant genes, including 86 that were previously assessed as tolerant and 1,153 that lack established disease annotation. We also define regions of missense depletion at high resolution. Notably, 1,482 genes have regions that are depleted of missense variants despite being tolerant of pLOF variants. Finally, we estimate that 3% of individuals have a clinically actionable genetic variant, and that 11,773 variants reported in ClinVar with unknown significance are likely to be deleterious cryptic splice sites. To facilitate variant interpretation and genetics-informed precision medicine, we make this resource of coding variation from the RGC-ME dataset publicly accessible through a variant allele frequency browser.


Asunto(s)
Variación Genética , Humanos , Variación Genética/genética , Secuenciación del Exoma , Mutación con Pérdida de Función/genética , Exoma/genética , Heterocigoto , Mutación Missense/genética , Frecuencia de los Genes , Alelos , Sistemas de Lectura Abierta/genética
2.
PLoS Comput Biol ; 19(10): e1011544, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37819942

RESUMEN

Emerging ultra-low coverage single-cell DNA sequencing (scDNA-seq) technologies have enabled high resolution evolutionary studies of copy number aberrations (CNAs) within tumors. While these sequencing technologies are well suited for identifying CNAs due to the uniformity of sequencing coverage, the sparsity of coverage poses challenges for the study of single-nucleotide variants (SNVs). In order to maximize the utility of increasingly available ultra-low coverage scDNA-seq data and obtain a comprehensive understanding of tumor evolution, it is important to also analyze the evolution of SNVs from the same set of tumor cells. We present Phertilizer, a method to infer a clonal tree from ultra-low coverage scDNA-seq data of a tumor. Based on a probabilistic model, our method recursively partitions the data by identifying key evolutionary events in the history of the tumor. We demonstrate the performance of Phertilizer on simulated data as well as on two real datasets, finding that Phertilizer effectively utilizes the copy-number signal inherent in the data to more accurately uncover clonal structure and genotypes compared to previous methods.


Asunto(s)
Neoplasias , Árboles , Humanos , Variaciones en el Número de Copia de ADN/genética , Neoplasias/genética , Análisis de Secuencia de ADN , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Análisis de la Célula Individual
3.
Nano Lett ; 23(24): 11424-11429, 2023 Dec 27.
Artículo en Inglés | MEDLINE | ID: mdl-38009634

RESUMEN

Dark excitons play a vital role in exciton condensation and optical properties of monolayer transition metal dichalcogenides (MTMDs). Previous literature mainly focuses on the detection of the energy of the dark exciton, while spatial detection and control are equally important but are less studied. Here we report that for MTMD embedded in a semiconductor microcavity and under a uniform in-plane magnetic field the spatial distribution of the dark exciton can be probed by measuring that of the cavity photon for small exciton-exciton interaction energy. Further, we propose to realize the anomalous exciton Hall effect by exploiting spatially inhomogeneous coupling of the bright and dark excitons under a Gaussian excitation beam. This effect occurs regardless of the exciton-exciton interaction, which will strengthen the diffusion of excitons in the excitation region. These results provide an improved understanding of the excitons in MTMDs, thereby facilitating their potential practical applications.

4.
Mol Biol Evol ; 39(7)2022 07 02.
Artículo en Inglés | MEDLINE | ID: mdl-35700225

RESUMEN

Transcription regulatory sequences (TRSs), which occur upstream of structural and accessory genes as well as the 5' end of a coronavirus genome, play a critical role in discontinuous transcription in coronaviruses. We introduce two problems collectively aimed at identifying these regulatory sequences as well as their associated genes. First, we formulate the TRS Identification problem of identifying TRS sites in a coronavirus genome sequence with prescribed gene locations. We introduce CORSID-A, an algorithm that solves this problem to optimality in polynomial time. We demonstrate that CORSID-A outperforms existing motif-based methods in identifying TRS sites in coronaviruses. Second, we demonstrate for the first time how TRS sites can be leveraged to identify gene locations in the coronavirus genome. To that end, we formulate the TRS and Gene Identification problem of simultaneously identifying TRS sites and gene locations in unannotated coronavirus genomes. We introduce CORSID to solve this problem, which includes a web-based visualization tool to explore the space of near-optimal solutions. We show that CORSID outperforms state-of-the-art gene finding methods in coronavirus genomes. Furthermore, we demonstrate that CORSID enables de novo identification of TRS sites and genes in previously unannotated coronavirus genomes. CORSID is the first method to perform accurate and simultaneous identification of TRS sites and genes in coronavirus genomes without the use of any prior information.


Asunto(s)
Infecciones por Coronavirus , Coronavirus , Coronavirus/genética , Infecciones por Coronavirus/genética , Humanos , ARN Mensajero/genética , ARN Viral/genética , Transcripción Genética
5.
J Environ Manage ; 335: 117530, 2023 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-36863150

RESUMEN

A comprehensive and scientific assessment of benthic ecosystem health is key to the rational selection of endogenous pollution reduction technologies for lakes. However, current assessments are mainly limited to biological indicators and ignore the actual benthic ecosystem situations, such as the impact of eutrophication and heavy metal pollution, which may lead to the one-sidedness of the evaluation results. In this study, taking Baiyangdian Lake, the largest shallow mesotrophic-eutrophic lake in the North China Plain, as an example, the chemical assessment index and biological integrity index were first combined to estimate the biological conditions, nutritional status and heavy metal pollution of lakes. The indicator system incorporated three biological assessments (benthic index of biotic integrity (B-IBI), submerged aquatic vegetation index of biological integrity (SAV-IBI) and microbial index of biological integrity (M-IBI)) and three chemical assessments (dissolved oxygen (DO), comprehensive trophic level index (TLI) and index of geoaccumulation (Igeo)). Twenty-three attributes of B-IBI, fourteen attributes of SAV-IBI and twelve attributes of M-IBI were screened by range, responsiveness, and redundancy tests to keep the core metrics that were significantly correlated with disturbance gradients or showed strong discriminatory power between reference and impaired sites. The assessment results of B-IBI, SAV-IBI, and M-IBI showed significant differences in the response to anthropogenic activities and seasonal change, among which the submerged plants showed more significant seasonal differences. It is difficult to reach a comprehensive conclusion regarding the benthic ecosystem health status based on a single biological community. In comparison with biological indicators, the score of chemical indicators is relatively low. DO, TLI and Igeo provide an essential supplement for the benthic ecosystem health assessment of lakes with eutrophication and heavy metal pollution problems. Using the new integrated assessment method, the benthic ecosystem health of Baiyangdian Lake was rated as fair, especially the northern parts of the lake adjacent to the inflow mouth of the Fu River, which were in poor condition, indicating that the lake has experienced anthropogenic disturbance, resulting in eutrophication, heavy metal pollution and biological community degradation. Whether it's spring or summer, the integrated assessment method provides a more plausible and comprehensive view of benthic ecosystem health under the pressure of increasing human activities and changing habitat and hydrological conditions, overcoming the narrow perspective and uncertainties of the single-index method. Thus, it can assist lake managers in providing technical support for ecological indication and restoration.


Asunto(s)
Ecosistema , Metales Pesados , Humanos , Lagos , Biomarcadores Ambientales , Monitoreo del Ambiente/métodos , China
6.
Bioinformatics ; 36(8): 2328-2336, 2020 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-31873730

RESUMEN

MOTIVATION: Variants identified by current genomic analysis pipelines contain many incorrectly called variants. These can be potentially eliminated by applying state-of-the-art filtering tools, such as Variant Quality Score Recalibration (VQSR) or Hard Filtering (HF). However, these methods are very user-dependent and fail to run in some cases. We propose VEF, a variant filtering tool based on decision tree ensemble methods that overcomes the main drawbacks of VQSR and HF. Contrary to these methods, we treat filtering as a supervised learning problem, using variant call data with known 'true' variants, i.e. gold standard, for training. Once trained, VEF can be directly applied to filter the variants contained in a given Variants Call Format (VCF) file (we consider training and testing VCF files generated with the same tools, as we assume they will share feature characteristics). RESULTS: For the analysis, we used whole genome sequencing (WGS) Human datasets for which the gold standards are available. We show on these data that the proposed filtering tool VEF consistently outperforms VQSR and HF. In addition, we show that VEF generalizes well even when some features have missing values, when the training and testing datasets differ in coverage, and when sequencing pipelines other than GATK are used. Finally, since the training needs to be performed only once, there is a significant saving in running time when compared with VQSR (4 versus 50 min approximately for filtering the single nucleotide polymorphisms of a WGS Human sample). AVAILABILITY AND IMPLEMENTATION: Code and scripts available at: github.com/ChuanyiZ/vef. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Asunto(s)
Genómica , Programas Informáticos , Genoma , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Polimorfismo de Nucleótido Simple , Secuenciación Completa del Genoma
7.
Exp Cell Res ; 370(1): 127-136, 2018 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-29913153

RESUMEN

Phosphoprotein associated with glycosphingolipid-enriched microdomains 1(PAG1) is a ubiquitous protein that is essential for the development and progression of various malignancies. A previous study in our laboratory confirmed that PAG1 plays an important role in modulating the inherent radioresistance of laryngeal cancer cells, but the underlying mechanisms are still poorly defined. In this study, we found that PAG1 was significantly increased in laryngeal cancer tissues compared to adjacent non-tumor tissues (P < 0.05). The expression of PAG1 was positively correlated with lymph node metastasis (P < 0.05) and TNM stage (P < 0.05). High expression of PAG1 also predicted a poor prognosis in patients with laryngeal cancer. Moreover, gain-of-function and loss-of-function studies showed that PAG1 overexpression was able to promote growth, increase migration and invasion, and enhance inherent radioresistance of laryngeal cancer cells. Mechanistic investigations revealed that the activation of STAT3 was required for PAG1-mediated inherent radioresistance of laryngeal cancer. Inhibition of STAT3 activity with a chemical inhibitor sensitized radioresistant cells to radiation. Importantly, PAG1-integrin ß1 complex was involved in the regulation of STAT3 activation. In addition, downregulation of PAG1 could suppress tumor growth and reverse inherent radioresistance in the nude mouse xenograft model. Taken together, these results suggested that PAG1 conferred inherent radioresistance by activating STAT3, which provided a novel therapeutic strategy for laryngeal cancer.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Neoplasias Laríngeas/genética , Proteínas de la Membrana/genética , Tolerancia a Radiación/genética , Factor de Transcripción STAT3/genética , Animales , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación hacia Abajo/genética , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Integrina beta1/genética , Metástasis Linfática/genética , Metástasis Linfática/patología , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos
8.
Biodegradation ; 29(1): 11-22, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29080942

RESUMEN

For municipal wastewater treatment, main stream biological nutrient removal (BNR) process is becoming more and more important. This lab-scale study, novel MBR_based BNR processes (named A2N-MBR and A2NO-MBR) were built. Comparison of the COD removal, results obtained demonstrated that COD removal efficiencies were almost the same in three processes, with effluent concentration all bellowed 30 mg L-1. However, the two-sludge systems (A2N-MBR and A2NO-MBR) had an obvious advantage over the A2/O for denitrification and phosphorus removal, with the average TP removal rates of 91.20, 98.05% and TN removal rates of 73.00, 79.49%, respectively, higher than that of 86.45 and 61.60% in A2/O process. Illumina Miseq sequencing revealed that Candidatus_Accumulibacter, which is capable of using nitrate as an electron acceptor for phosphorus and nitrogen removal simultaneously, was the dominant phylum in both A2N-MBR and A2NO-MBR process, accounting for 28.74 and 23.98%, respectively. Distinguishingly, major organism groups related to nitrogen and phosphorus removal in A2/O system were Anaerolineaceae_uncultured, Saprospiraceae_uncultured and Thauera, with proportions of 11.31, 8.56 and 5.00%, respectively. Hence, the diversity of dominant PAOs group was likely responsible for the difference in nitrogen and phosphorus removal in the three processes.


Asunto(s)
Bacterias/metabolismo , Reactores Biológicos/microbiología , Membranas Artificiales , Nitrógeno/aislamiento & purificación , Fósforo/aislamiento & purificación , Aerobiosis , Amoníaco/metabolismo , Anaerobiosis , Biodegradación Ambiental , Análisis de la Demanda Biológica de Oxígeno , Desnitrificación , Nitratos/metabolismo , Nitrificación , Filogenia , Aguas del Alcantarillado/microbiología , Aguas Residuales/microbiología
9.
Water Sci Technol ; 78(8): 1741-1752, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30500798

RESUMEN

An alternate anaerobic/anoxic-aerobic double membrane bioreactors process (A2N-DMBR) was proposed to improve denitrifying phosphorus removal efficiency. The system was operated for 70 d under different nitrogen/phosphorus (N/P) ratios with synthetic wastewater to present the performance evaluation of nutrients removal and microbial community structure in the A2N-DMBR process. The results showed that when the influent total phosphorus (TP) was 6.4 mg/L, the corresponding N/P ratio of 8.8, the high removal capacity of nitrogen and phosphorus could be achieved with the average effluent TP and total nitrogen (TN) concentration of 0.8 mg/L and 12.0 mg/L, respectively. Periodical test showed that pH and oxidation-reduction potential (ORP) could be used as control parameters for anaerobic phosphate release, and ORP was also closely related with the phosphate uptake in anoxic phase. The high-throughput sequencing analysis revealed that the Proteobacteria and Xanthomonadales-nobank related to biological nitrogen and phosphorus removal was domination bacteria at phylum and genus level in A2N-DMBR system, with the proportion of 42.5% and 39.1%, respectively. Furthermore, Dechloromonas, which was further detected as putative denitrifying phosphorus accumulating organisms (DPAOs), was enriched (9.9%) in the system.


Asunto(s)
Reactores Biológicos , Fósforo/análisis , Eliminación de Residuos Líquidos/métodos , Contaminantes Químicos del Agua/análisis , Desnitrificación , Nitrógeno , Aguas del Alcantarillado
10.
Eur J Radiol ; 166: 111003, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37506477

RESUMEN

PURPOSE: To assess the continuous-time random-walk (CTRW) model's diagnostic value in breast lesions and to explore the associations between the CTRW parameters and breast cancer pathologic factors. METHOD: This retrospective study included 85 patients (70 malignant and 18 benign lesions) who underwent 3.0T MRI examinations. Diffusion-weighted images (DWI) were acquired with 16b-values to fit the CTRW model. Three parameters (Dm, α, and ß) derived from CTRW and apparent diffusion coefficient (ADC) from DWI were compared among the benign/malignant lesions, molecular prognostic factors, and molecular subtypes by Mann-Whitney U test. Spearman correlation was used to evaluate the associations between the parameters and prognostic factors. The diagnostic performance was assessed by the area under the receiver operating characteristic curve (AUC) based on the diffusion parameters. RESULTS: All parameters, ADC, Dm, α, and ß were significantly lower in the malignant than benign lesions (P < 0.05). The combination of all the CTRW parameters (Dm, α, and ß) provided the highest AUC (0.833) and the best sensitivity (94.3%) in differentiating malignant status. And the positive status of estrogen receptor (ER) and progesterone receptor (PR) showed significantly lower ß compared with the negative counterparts (P < 0.05). The high Ki-67 expression produced significantly lower Dm and ADC values (P < 0.05). Additionally, combining multiple CTRW parameters improved the performance of diagnosing molecular subtypes of breast cancer. Moreover, Spearman correlations analysis showed that ß produced significant correlations with ER, PR and Ki-67 expression (P < 0.05). CONCLUSIONS: The CTRW parameters could be used as non-invasive quantitative imaging markers to evaluate breast lesions.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Pronóstico , Estudios Retrospectivos , Antígeno Ki-67 , Sensibilidad y Especificidad , Interpretación de Imagen Asistida por Computador/métodos , Reproducibilidad de los Resultados , Imagen por Resonancia Magnética , Imagen de Difusión por Resonancia Magnética/métodos , Receptores de Estrógenos , Mama/patología
11.
bioRxiv ; 2023 Nov 02.
Artículo en Inglés | MEDLINE | ID: mdl-37214792

RESUMEN

Coding variants that have significant impact on function can provide insights into the biology of a gene but are typically rare in the population. Identifying and ascertaining the frequency of such rare variants requires very large sample sizes. Here, we present the largest catalog of human protein-coding variation to date, derived from exome sequencing of 985,830 individuals of diverse ancestry to serve as a rich resource for studying rare coding variants. Individuals of African, Admixed American, East Asian, Middle Eastern, and South Asian ancestry account for 20% of this Exome dataset. Our catalog of variants includes approximately 10.5 million missense (54% novel) and 1.1 million predicted loss-of-function (pLOF) variants (65% novel, 53% observed only once). We identified individuals with rare homozygous pLOF variants in 4,874 genes, and for 1,838 of these this work is the first to document at least one pLOF homozygote. Additional insights from the RGC-ME dataset include 1) improved estimates of selection against heterozygous loss-of-function and identification of 3,459 genes intolerant to loss-of-function, 83 of which were previously assessed as tolerant to loss-of-function and 1,241 that lack disease annotations; 2) identification of regions depleted of missense variation in 457 genes that are tolerant to loss-of-function; 3) functional interpretation for 10,708 variants of unknown or conflicting significance reported in ClinVar as cryptic splice sites using splicing score thresholds based on empirical variant deleteriousness scores derived from RGC-ME; and 4) an observation that approximately 3% of sequenced individuals carry a clinically actionable genetic variant in the ACMG SF 3.1 list of genes. We make this important resource of coding variation available to the public through a variant allele frequency browser. We anticipate that this report and the RGC-ME dataset will serve as a valuable reference for understanding rare coding variation and help advance precision medicine efforts.

12.
Ann Transl Med ; 10(6): 309, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35433975

RESUMEN

Background: There has always been controversy about the choice of anterior approach or posterior approach for the surgical approach of thoracolumbar burst fractures (TBFs). The aim of this study was to systematically evaluate the efficacy and safety of anterior and posterior approaches in the treatment of TBFs. Methods: Multiple databases including PubMed, Excerpt Medica Database (Embase), Cochrane Library, and Web of Science (WOS) were used to search for relevant studies, namely full-text articles comparing the anterior versus posterior approach for the treatment of TBFs, which based on population, intervention, control, outcome, and study (PICOS) framework. Review Manager 5.4 was used to assess the effects of the results among selected studies. The risk of bias of the trials was assessed using the Newcastle Ottawa scale (NOS) and the Cochrane Collaboration's tool. Forest plots and funnel plots were also generated for the included articles. Results: Finally, 723 patients were included in 13 studies which satisfied the eligibility criteria, funnel plots and Egger's test showed that there was no significant bias in the publications. There were no differences in terms of length of stay [mean difference (MD): -1.31, (-5.31, 2.69); P=0.52], hospitalization expenses [standardized mean difference (SMD): 1.26, (-0.38, 2.89); P=0.13], and return to work between the anterior approach and posterior approach. However, the posterior approach had the advantages of better Cobb angle correction [MD: 2.06, (0.17, 3.94); P=0.03], shorter operation time [MD: 58.29, (35.39, 81.18); P<0.00001], and lower estimated blood loss [MD: 185.92, (131.76, 240.07); P<0.00001]. Discussion: The posterior approach appeared to be superior to the anterior approach in the treatment of TBFs. However, more high-quality randomized controlled trials should be conducted to confirm the conclusions of this study and guide clinical decision-making.

13.
Front Surg ; 9: 875475, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35574530

RESUMEN

Objectives: This study aimed to introduce a sternoclavicular joint (SCJ)-specific plate for the treatment of medial-end clavicle fracture and evaluate the clinical and radiological results of this method. Methods: From January 2006 to December 2020, 31 patients with displaced medial-end clavicle fractures were included in this study, with 8 patients with accompanying SCJ dislocation. Abduction and forward elevation of the shoulder, the Visual Analogue Scale (VAS), and the American Shoulder and Elbow Surgeons Score (ASES) were used for evaluation before index surgery and at the latest follow-up. Results: After an average of 98.5 (range, 13 to 171) months, the mean VAS significantly decreased from 6.8 ± 1.0 preoperatively to 0.9 ± 0.8 at the latest follow-up (P < 0.001). The mean ASES score significantly increased from 34.3 ± 7.8 preoperatively to 90.2 ± 4.9 at the latest follow-up (P < 0.001). The mean abduction of the shoulder significantly increased from 72.1 ± 6.6 preoperatively to 169.5 ± 8.5 at the latest follow-up (P < 0.001). The mean forward elevation of the shoulder significantly increased from 97.1 ± 11.0 preoperatively to 163.1 ± 11.5 at the latest follow-up (P < 0.001). The union of all fractures was achieved, and all implants were removed. No loose or breakage of implants was observed. No vascular or nerve damage occurred during the operation. Conclusions: This SCJ-specific plate provided excellent long-term results for the treatment of displaced medial-end clavicle fractures and was an alternative implant for medial-end clavicle fractures with or without small or comminuted medial fragments, especially those associated with SCJ dislocation.

14.
Zhongguo Gu Shang ; 35(8): 752-6, 2022 Aug 25.
Artículo en Zh | MEDLINE | ID: mdl-35979769

RESUMEN

OBJECTIVE: To explore the clinical effect of Kirschner wire retractor-assisted reduction and inverted insertion of elastic nail in the treatment of children's irreducible subradial 1/3 fractures. METHODS: A total of 34 children with irreducible subradial 1/3 fractures treated by surgery from August 2016 to December 2020 were retrospective analyzed. Among them, 16 cases underwent Kirschner wire retractor-assisted closed reduction and percutaneous elastic intramedullary nailing with inverted insertion(observation group), 10 males and 6 females, aged from 4 to 10 years old with an average of(6.0±0.4)years;18 cases underwent open reduction and plate internal fixation (control group), 11 males and 7 females, the age from 3 to 10 years with an average of(7.0±0.5) years. The operation time, intraoperative blood loss, hospital stay, incision length, fracture healing time and complications of the two groups were observed and the wrist function was evaluated by Cooney wrist joint score. RESULTS: All patients were followed up for 3-12 years old with an average of (11.40±0.48) months in the observation group and 4-13 months with an average of (11.50±0.39) months in the control group. Bone healing was achieved in all patients, and there was no incision infection in both groups. The operation time, intraoperative blood loss, hospital stay and incision length in observation groups were lower than those of control group (P<0.05). There was no significant difference in the fracture healing time between two groups(P>0.05). There was no significant difference in postoperative healing and recovery of wrist function between groups(P>0.05). CONCLUSION: Compared with open reduction and plate internal fixation, Kirschner wire retractor-assisted reduction and percutaneous elastic intramedullary nail fixation for irreducible subradial radial 1/3 fractures has the advantages of less trauma, shorter operation time, less blood loss, and satisfactory short-term clinical results.


Asunto(s)
Fijación Intramedular de Fracturas , Fracturas del Radio , Pérdida de Sangre Quirúrgica , Clavos Ortopédicos , Hilos Ortopédicos , Niño , Preescolar , Femenino , Fijación Interna de Fracturas/métodos , Fijación Intramedular de Fracturas/métodos , Curación de Fractura , Humanos , Masculino , Fracturas del Radio/cirugía , Estudios Retrospectivos , Resultado del Tratamiento
15.
Nat Commun ; 12(1): 2204, 2021 04 13.
Artículo en Inglés | MEDLINE | ID: mdl-33850139

RESUMEN

Intra-tumor heterogeneity renders the identification of somatic single-nucleotide variants (SNVs) a challenging problem. In particular, low-frequency SNVs are hard to distinguish from sequencing artifacts. While the increasing availability of multi-sample tumor DNA sequencing data holds the potential for more accurate variant calling, there is a lack of high-sensitivity multi-sample SNV callers that utilize these data. Here we report Moss, a method to identify low-frequency SNVs that recur in multiple sequencing samples from the same tumor. Moss provides any existing single-sample SNV caller the ability to support multiple samples with little additional time overhead. We demonstrate that Moss improves recall while maintaining high precision in a simulated dataset. On multi-sample hepatocellular carcinoma, acute myeloid leukemia and colorectal cancer datasets, Moss identifies new low-frequency variants that meet manual review criteria and are consistent with the tumor's mutational signature profile. In addition, Moss detects the presence of variants in more samples of the same tumor than reported by the single-sample caller. Moss' improved sensitivity in SNV calling will enable more detailed downstream analyses in cancer genomics.


Asunto(s)
ADN de Neoplasias/genética , Neoplasias Hepáticas/genética , Nucleótidos , Algoritmos , Carcinoma Hepatocelular , Neoplasias Colorrectales/genética , Frecuencia de los Genes , Genómica/métodos , Humanos , Leucemia Mieloide Aguda/genética , Mutación , Polimorfismo de Nucleótido Simple
16.
Nat Commun ; 12(1): 6728, 2021 11 18.
Artículo en Inglés | MEDLINE | ID: mdl-34795232

RESUMEN

Genes in SARS-CoV-2 and other viruses in the order of Nidovirales are expressed by a process of discontinuous transcription which is distinct from alternative splicing in eukaryotes and is mediated by the viral RNA-dependent RNA polymerase. Here, we introduce the DISCONTINUOUS TRANSCRIPT ASSEMBLYproblem of finding transcripts and their abundances given an alignment of paired-end short reads under a maximum likelihood model that accounts for varying transcript lengths. We show, using simulations, that our method, JUMPER, outperforms existing methods for classical transcript assembly. On short-read data of SARS-CoV-1, SARS-CoV-2 and MERS-CoV samples, we find that JUMPER not only identifies canonical transcripts that are part of the reference transcriptome, but also predicts expression of non-canonical transcripts that are supported by subsequent orthogonal analyses. Moreover, application of JUMPER on samples with and without treatment reveals viral drug response at the transcript level. As such, JUMPER enables detailed analyses of Nidovirales transcriptomes under varying conditions.


Asunto(s)
COVID-19/genética , SARS-CoV-2/genética , Empalme Alternativo/genética , Perfilación de la Expresión Génica , Humanos , Transcriptoma/genética
17.
ANZ J Surg ; 91(4): 653-657, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33522678

RESUMEN

BACKGROUND: The treatment of traumatic sternoclavicular joint (SCJ) dislocation (SCJD) with internal fixation has been reported with good short-term results, but data on its long-term results are scarce. METHODS: Patients with traumatic SCJD treated with an SCJ-specific plate between January 2003 and January 2018 were evaluated retrospectively. All implants were routinely removed. Data from radiography, the American Shoulder and Elbow Surgeons score, the visual analogue scale and abduction and forward elevation of the shoulder were collected and evaluated before the index surgery, at implant removal and at the latest follow-up. RESULTS: A total of 22 patients were included in this study with a mean follow-up period of 94.8 months. All patients maintained good reduction after the index surgery and implant removal. The visual analogue scale significantly improved from 7.1 ± 1.3 before the index surgery to 0.9 ± 1.0 at implant removal (P < 0.001) and to 1.0 ± 1.1 at the latest follow-up (P < 0.001); the American Shoulder and Elbow Surgeons score significantly improved from 37.9 ± 10.1 to 90.8 ± 7.8 (P < 0.001) and to 86.7 ± 8.6; and both abduction and forward elevation of the shoulder significantly improved at the latest follow-up (P < 0.001). There was no significant difference in the clinical results after implant removal. CONCLUSION: Traumatic SCJD treated with an SCJ-specific plate appeared to be efficient, with satisfactory clinical and radiological results at long-term follow-up.


Asunto(s)
Luxaciones Articulares , Articulación Esternoclavicular , Placas Óseas , Fijación Interna de Fracturas , Humanos , Luxaciones Articulares/diagnóstico por imagen , Luxaciones Articulares/cirugía , Estudios Retrospectivos , Articulación Esternoclavicular/diagnóstico por imagen , Articulación Esternoclavicular/cirugía , Resultado del Tratamiento
18.
J Phys Condens Matter ; 32(36): 365402, 2020 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-32380484

RESUMEN

Fulde-Ferrell (FF) state is an exotic superconducting or superfluid state, characterized by Cooper pairs with a finite center-of-mass momentum, and it has been intensively investigated in spinful systems, but the spin population imbalance is usually necessary. Here we propose a model to realize and modulate the spinless FF superfluid, namely, Haldane model with nearest-neighbor interaction. The FF state appears when the space-inversion and time-reversal symmetries are broken simultaneously, and there exists the first order phase transition. A higher Berezinskii-Kosterlitz-Thouless transition temperature is obtained at larger absolute value of Peierls phase and smaller energy offset of the sublattices. Our proposal provides a feasible option for experimental researchers to detect the FF superfluid.

19.
Chemosphere ; 243: 125300, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31734595

RESUMEN

The removal of nutrients in a combined modified University of Cape Town and post-anoxic/aerobic-membrane bioreactor (UCT-A/MBR) was investigated. Denitrifying phosphorus removal (DPR) and nitrate-dependent anaerobic ferrous oxidation (NAFO) were applied to enhance the nutrient removal performances. The results showed that NAFO with the addition of Fe(II) and DPR could promote nitrogen and phosphorus removal. The total nitrogen removal efficiency gradually increased from 71.05 ±â€¯2.00% to 73.84 ±â€¯1.74% and 75.70 ±â€¯1.47% with no Fe(II) addition, addition to the post-anoxic tank, and addition to the anoxic tank, and the total phosphorus removal efficiency increased from 89.37 ±â€¯1.91% to 95.21 ±â€¯0.85% and 96.01 ±â€¯1.10%, respectively. Gene sequencing was conducted, and Saprospiraceae was determined to be the dominant DPR-related bacteria, with its abundance increasing from 16.31% to 22.45% after Fe(II) addition. Additionally, the proportion of the NAFO-related bacteria Azospira increased from 0.58% to 1.91% after Fe(II) addition. The microbial succession caused by the addition of Fe(II) may have resulted in the enhanced removal performance.


Asunto(s)
Reactores Biológicos/normas , Desnitrificación , Compuestos Ferrosos/farmacología , Nutrientes/aislamiento & purificación , Fósforo/aislamiento & purificación , Bacterias/efectos de los fármacos , Reactores Biológicos/microbiología , Aguas del Alcantarillado/microbiología , Eliminación de Residuos Líquidos/métodos
20.
Environ Sci Pollut Res Int ; 27(32): 40483-40494, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32666456

RESUMEN

The single-stage partial nitritation-anammox (PN/A) process is severely limited by a long start-up time and unstable removal efficiency. In this study, PN/A was developed in 67 days in a novel packed bed equipped with porous bio-carriers by gradually increasing the influent nitrogen loading rate (0.15-0.73 kg-N m-3·d-1) and controlling the dissolved oxygen (< 1.2 mg L-1). An average ammonium nitrogen removal efficiency (ARE) and total nitrogen removal efficiency (TNR) of 87.01 and 72.41%, respectively, were obtained. This represents a reliable alternative method of achieving rapid PN/A start-up. The results of 16S rRNA sequencing showed that Proteobacteria and Planctomycetes, with which ammonia-oxidizing bacteria and anammox bacteria were affiliated, accounted for 38.8%, representing the dominant phylum in the system after acclimation. The abundance of Nitrosomonas and Candidatus Brocadia increased by 16 and 1.79%, respectively. The results of metagenomics and metatranscriptomics revealed that the nitrite oxidation process was blocked by the transcriptional suppression of nitrite oxidoreductase and the entire nitrogen metabolism process was dominated by the partial nitritation and anammox process. Moreover, a high abundance of heterotrophic bacteria with potential for nitrogen removal was detected. In the nitrogen cycle, a widespread nitrite-accumulated denitrification helps to form a nitrite loop, which promotes the efficiency of total nitrogen removal. This is crucial for further improving the nitrogen removal mechanism in the PN/A system.


Asunto(s)
Desnitrificación , Nitrógeno , Reactores Biológicos , Oxidación-Reducción , ARN Ribosómico 16S/genética
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