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1.
iScience ; 27(9): 110623, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39228791

RESUMEN

Machine learning has the potential to be a powerful tool in the fight against antimicrobial resistance (AMR), a critical global health issue. Machine learning can identify resistance mechanisms from DNA sequence data without prior knowledge. The first step in building a machine learning model is a feature extraction from sequencing data. Traditional methods like single nucleotide polymorphism (SNP) calling and k-mer counting yield numerous, often redundant features, complicating prediction and analysis. In this paper, we propose PanKA, a method using the pangenome to extract a concise set of relevant features for predicting AMR. PanKA not only enables fast model training and prediction but also improves accuracy. Applied to the Escherichia coli and Klebsiella pneumoniae bacterial species, our model is more accurate than conventional and state-of-the-art methods in predicting AMR.

2.
Genome Biol ; 25(1): 209, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39107817

RESUMEN

Pangenome inference is an indispensable step in bacterial genomics, yet its scalability poses a challenge due to the rapid growth of genomic collections. This paper presents PanTA, a software package designed for constructing pangenomes of large bacterial datasets, showing unprecedented efficiency levels multiple times higher than existing tools. PanTA introduces a novel mechanism to construct the pangenome progressively without rebuilding the accumulated collection from scratch. The progressive mode is shown to consume orders of magnitude less computational resources than existing solutions in managing growing datasets. The software is open source and is publicly available at https://github.com/amromics/panta and at 10.6084/m9.figshare.23724705 .


Asunto(s)
Genoma Bacteriano , Programas Informáticos , Genómica/métodos , Bacterias/genética , Filogenia
3.
BMC Genomics ; 25(1): 709, 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39039439

RESUMEN

Whole genome analysis for microbial genomics is critical to studying and monitoring antimicrobial resistance strains. The exponential growth of microbial sequencing data necessitates a fast and scalable computational pipeline to generate the desired outputs in a timely and cost-effective manner. Recent methods have been implemented to integrate individual genomes into large collections of specific bacterial populations and are widely employed for systematic genomic surveillance. However, they do not scale well when the population expands and turnaround time remains the main issue for this type of analysis. Here, we introduce AMRomics, an optimized microbial genomics pipeline that can work efficiently with big datasets. We use different bacterial data collections to compare AMRomics against competitive tools and show that our pipeline can generate similar results of interest but with better performance. The software is open source and is publicly available at https://github.com/amromics/amromics under an MIT license.


Asunto(s)
Genoma Bacteriano , Genómica , Programas Informáticos , Flujo de Trabajo , Genómica/métodos , Biología Computacional/métodos , Bacterias/genética , Genoma Microbiano , Farmacorresistencia Bacteriana/genética
4.
Cureus ; 16(4): e59029, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38800146

RESUMEN

BACKGROUND:  Supracondylar humeral fractures are the most prevalent elbow fractures in pediatric patients. Current treatment modalities typically involve closed reduction and fixation using percutaneous Kirschner wires. The lateral cross-wiring technique has demonstrated favorable functional and cosmetic outcomes, thereby reducing the incidence of ulnar nerve injury. OBJECTIVES:  This study aimed to assess the efficacy of the lateral cross-wiring technique in achieving optimal functional and cosmetic recovery while mitigating the risk of ulnar nerve injury in pediatric patients with displaced supracondylar humeral fractures. MATERIALS AND METHODS: A prospective analysis was conducted on 48 patients who underwent lateral cross-wiring for displaced supracondylar fractures (Gartland type III, including extension and flexion types) of the humerus. Follow-up assessments were performed over a minimum period of eight months post-surgery. RESULTS: Among the 48 patients, all demonstrated satisfactory restoration of the carrying angle and functional ability postoperatively. Notably, no iatrogenic cases of radial or ulnar nerve injury were observed during the follow-up period. CONCLUSION:  The lateral cross-wiring technique emerges as an effective treatment option for displaced supracondylar fractures of the humerus in pediatric patients. It facilitates both functional and cosmetic recovery while concurrently reducing the risk of ulnar nerve injury, thus warranting consideration in the management of such fractures.

5.
Spine Deform ; 12(5): 1311-1318, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38801508

RESUMEN

PURPOSE: This study evaluated the relationship between maximal axial vertebra rotation (maxAVR) and other clinical and radiological indexes, compared to apical vertebra rotation (AVR) in idiopathic adolescent scoliosis (AIS). METHODS: Forty consecutive patients of AIS with Cobb angle of major curve > 40° were included. They were scanned by an EOS imaging system and had trunk rotational angle (TRA) measured by scoliometer. The correlation between variables was assessed using Pearson's correlation coefficient and loaded onto a meta-analysis model. RESULTS: There were (34 girls and 6 boys) with an average age of 13.8 ± 1.6 years. AVR was maxAVR in only 47.5% (19/40) cases of the major curves and 42.3% (11/26) cases of the minor curves. The correlation between maxAVR and TRA was significantly higher than the correlation between AVR and TRA for the MT curves (p = 0.0001) and TL/L curves (p = 0.0001). On multivariate regression analysis, the magnitude of maxAVR showed a significant correlation with TRA (p = 0.0002), Cobb angle (p = 0.001), and coronal deformity angular ratio (C-DAR) (p = 0.027). CONCLUSIONS: The apical vertebra was not the most rotated in most cases. The correlation between maxAVR and TRA was significantly higher than the correlation between AVR and TRA. Moreover, the maxAVR was multivariately related to TRA, Cobb angle, and C-DAR. LEVEL OF EVIDENCE: Level II, diagnostic.


Asunto(s)
Escoliosis , Humanos , Escoliosis/diagnóstico por imagen , Escoliosis/fisiopatología , Adolescente , Femenino , Masculino , Rotación , Niño , Vértebras Torácicas/diagnóstico por imagen , Vértebras Torácicas/fisiopatología , Radiografía/métodos , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/fisiopatología , Columna Vertebral/diagnóstico por imagen , Columna Vertebral/fisiopatología
6.
Cureus ; 16(4): e58437, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38765341

RESUMEN

Purpose Understanding the relevant risk factors for patellar instability and the clinical and radiographic tests necessary to determine optimal treatment. This case series intends to evaluate arthroscopic indications in the treatment of patellar instability in children. Methods From 2013 to 2021, 33 patients (seven to 16 years of age) with 35 knees sustaining first-time dislocation with loose bodies, recurrent dislocation or subluxation, and habitual dislocation were arthroscopically operated on according to the flow chart. Periods of follow-up were two to 10 years (avg. 5.5 years). Follow-up assessment included the recurrence, complications (joint stiffness and excessive reduction), and the final function outcomes by using the Kujala score. Results Among 35 knees, there were two (5.7%) first dislocations, 30 (85.7%) recurrent dislocations, and three (8.6%) habitual dislocations, lateral release 27/35 (77.1%), medial reefing 23/35 (65.7%), reconstruction of the medial patellofemoral ligament (MPFL) 12/35 (34.3%). The major complication was a knee of extensive stiffness after medial reefing and lateral release. Recurrence was in 4/35 (11.4%) of knees, not correlated to lateral release (p=0.21), medial reefing, or reconstruction of MPFL (p=0.07); in about 23 knees of medial reefing, recurrence was significantly correlated to number of knots (p=0.045). The final functional results according to Kujala were 88-100 (avg. 95.5). Conclusions This study showed the role of arthroscopy in both medial reefing and reconstruction of MPFL in children by low recurrence rate and high Kujala score at final follow-up. There was no significant correlation between recurrence and the procedures as arthroscopic indications counted on the flow chart.

7.
BMC Bioinformatics ; 25(1): 193, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38755527

RESUMEN

We have developed AMRViz, a toolkit for analyzing, visualizing, and managing bacterial genomics samples. The toolkit is bundled with the current best practice analysis pipeline allowing researchers to perform comprehensive analysis of a collection of samples directly from raw sequencing data with a single command line. The analysis results in a report showing the genome structure, genome annotations, antibiotic resistance and virulence profile for each sample. The pan-genome of all samples of the collection is analyzed to identify core- and accessory-genes. Phylogenies of the whole genome as well as all gene clusters are also generated. The toolkit provides a web-based visualization dashboard allowing researchers to interactively examine various aspects of the analysis results. Availability: AMRViz is implemented in Python and NodeJS, and is publicly available under open source MIT license at https://github.com/amromics/amrviz .


Asunto(s)
Genoma Bacteriano , Genómica , Programas Informáticos , Genómica/métodos , Farmacorresistencia Bacteriana/genética , Filogenia , Bacterias/genética , Bacterias/efectos de los fármacos , Antibacterianos/farmacología
8.
Eur Spine J ; 33(6): 2213-2221, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38581434

RESUMEN

PURPOSE: Lumbar spinal stenosis (LSS) is common in our aging population resulting in pain and functional impairment. Recent advances in pain research have identified several single nucleotide polymorphisms (SNP) associated with inter-individual symptom and treatment response. The goal of the current study was to investigate the association of SNPs in Neuropeptide Y (NPY) and Catechol-O-methyltransferase (COMT) with pain, function, and treatment outcomes in Lumbar spinal stenosis (LSS) patients receiving non-surgical treatments. METHODS: An exploratory observational biomarker study was performed ancillary to a previously published clinical trial evaluating three different non-surgical treatments for LSS. Saliva samples were obtained for single nucleotide polymorphism genotyping and blood samples were collected for NPY protein. Data on pain and function collected as part of the clinical trial at baseline, 2 and 6 months were examined for association with known polymorphisms in NPY and COMT. RESULTS: Subjects with the NPY rs16147 TT genotype exhibited higher baseline symptom severity but also a higher likelihood of responding to non-surgical treatments. Subjects with the COMT rs4680 GG genotype also exhibited higher baseline symptom severity but did not demonstrate greater response to treatment. CONCLUSIONS: NPY rs16147 and COMT rs4680 are important potential biomarkers associated with pain and function. NPY genotype may be useful in predicting response to non-surgical treatments in older adults with LSS.


Asunto(s)
Catecol O-Metiltransferasa , Vértebras Lumbares , Neuropéptido Y , Polimorfismo de Nucleótido Simple , Estenosis Espinal , Humanos , Estenosis Espinal/genética , Femenino , Masculino , Anciano , Catecol O-Metiltransferasa/genética , Resultado del Tratamiento , Neuropéptido Y/genética , Persona de Mediana Edad , Dolor/genética , Dolor/etiología , Anciano de 80 o más Años
9.
Am J Emerg Med ; 79: 212-213, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38462426

RESUMEN

BACKGROUND: Foam tape is commonly used in the emergency department as a dressing over chest tubes owing to its occlusive and compressible properties. There is a paucity of data regarding the incidence of significant cutaneous reactions to this material. We conducted a prospective trial to evaluate the incidence of dermatitis following application of foam tape to the upper arm of a cohort of healthy volunteers. METHODS: This was a prospective, interventional trial. We enrolled a cohort of consenting, healthy physicians, nurses, and ancillary staff at a teaching facility who did not have known hypersensitivity to foam tape. Study investigators applied a 2 × 2 inch piece of 3 M microfoam adhesive to the medial aspect of each subject's upper arm. The contralateral arm served as a reference for comparison. The adhesive remained in place for 48 h and the study authors assessed patients utilizing the previously validated Cutaneous Irritancy Scoring System (CISS). Categorical variables analyzed by chi-square, continuous variables with t-tests. RESULTS: There were 40 subjects in the study group; 52% female, mean age 40±7 years, 55% non-White race. 10/40 (25%; 95%CI[14%, 41%]) of subjects had erythema; 9/40 (22%) had an erythema score of 1 and 1/40 (2.5%) had a score of 2. With respect to edema, 2/40 (5%; 95% CI[1%,18%]); 1/40(2.5%) had an edema score of 1, and 1/40(2.5%) had a score of 2. There were 9/40 subjects with an irritancy score > 0; (22%; 95%CI[12%,38%]); 7/40(18%) had an irritancy score of 1, and 2/4(5.0%) had a score of 2. In terms of the severity score, 10/40 (25%; 95%CI[14%, 41%]) had a score > 0; 9/40(22%) had a score of 1, and 1/40(2.5%) had a score of 2. Overall, 10/40 (25%; 95%CI[14%, 41%]) of subjects had at least one positive measure of a reaction of any kind. Subjects' age, gender and race were not found to be statistically significantly associated with the incidence of erythema, edema, or irritancy. In addition, these characteristics were not statistically significantly associated with severity score > 0. The p values for all the above bivariate analyses were > 0.05. CONCLUSIONS: Cutaneous reactions occurred in 25% of healthy volunteers after the application of foam tape to the arm. Patient characteristics were not associated with risk of a skin reaction. CLINICAL TRIALS REGISTRATION: #NCT06059417.


Asunto(s)
Dermatitis , Eritema , Humanos , Femenino , Adulto , Persona de Mediana Edad , Masculino , Estudios Prospectivos , Voluntarios Sanos , Incidencia , Eritema/inducido químicamente , Eritema/epidemiología , Adhesivos , Edema
10.
Heliyon ; 10(6): e27043, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38509882

RESUMEN

Despite the raised awareness of the role of pharmacogenomic (PGx) in personalized medicines for COVID-19, data for COVID-19 drugs is extremely scarce and not even a publication on this topic for post-COVID-19 medications to date. In the current study, we investigated the genetic variations associated with COVID-19 and post-COVID-19 therapies by using whole genome sequencing data of the 1000 Vietnamese Genomes Project (1KVG) in comparison with other populations retrieved from the 1000 Genomes Project Phase 3 (1KGP3) and the Genome Aggregation Database (gnomAD). Moreover, we also evaluated the risk of drug interactions in comorbid COVID-19 and post-COVID-19 patients based on pharmacogenomic profiles of drugs using a computational approach. For COVID-19 therapies, variants related to the response of two causal treatment agents (tolicizumab and ritonavir) and antithrombotic drugs are common in the Vietnamese cohort. Regarding post-COVID-19, drugs for mental manipulations possess the highest number of clinical annotated variants carried by Vietnamese individuals. Among the superpopulations, East Asian populations shared the most similar genetic structure with the Vietnamese population, whereas the African population showed the most difference. Comorbid patients are at an increased drug-drug interaction (DDI) risk when suffering from COVID-19 and after recovering as well due to a large number of potential DDIs which have been identified. Our results presented the population-specific understanding of the pharmacogenomic aspect of COVID-19 and post-COVID-19 therapy to optimize therapeutic outcomes and promote personalized medicine strategy. We also partly clarified the higher risk in COVID-19 patients with underlying conditions by assessing the potential drug interactions.

11.
PLoS One ; 19(2): e0288526, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38324614

RESUMEN

It was necessary to have a tool that could predict the amount of protein and optimize the gene sequences to produce recombinant proteins efficiently. The Transim model published by Tuller et al. in 2018 can calculate the translation rate in E. coli using features on the mRNA sequence, achieving a Spearman correlation with the amount of protein per mRNA of 0.36 when tested on the dataset of operons' first genes in E. coli K-12 MG1655 genome. However, this Spearman correlation was not high, and the model did not fully consider the features of mRNA and protein sequences. Therefore, to enhance the prediction capability, our study firstly tried expanding the testing dataset, adding genes inside the operon, and using the microarray of the mRNA expression data set, thereby helping to improve the correlation of translation rate with the amount of protein with more than 0.42. Next, the applicability of 6 traditional machine learning models to calculate a "new translation rate" was examined using initiation rate and elongation rate as inputs. The result showed that the SVR algorithm had the most correlated new translation rates, with Spearman correlation improving to R = 0.6699 with protein level output and to R = 0.6536 with protein level per mRNA. Finally, the study investigated the degree of improvement when combining more features with the new translation rates. The results showed that the model's predictive ability to produce a protein per mRNA reached R = 0.6660 when using six features, while the correlation of this model's final translation rate to protein level was up to R = 0.6729. This demonstrated the model's capability to predict protein expression of a gene, rather than being limited to predicting expression by an mRNA and showed the model's potential for development into gene expression predicting tools.


Asunto(s)
Escherichia coli K12 , Escherichia coli , ARN Mensajero/genética , ARN Mensajero/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Escherichia coli K12/genética , Escherichia coli K12/metabolismo , Genoma , Proteínas Recombinantes/metabolismo , Biosíntesis de Proteínas/genética
12.
BMC Genomics ; 25(1): 52, 2024 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-38212682

RESUMEN

BACKGROUND: Most skin-related traits have been studied in Caucasian genetic backgrounds. A comprehensive study on skin-associated genetic effects on underrepresented populations such as Vietnam is needed to fill the gaps in the field. OBJECTIVES: We aimed to develop a computational pipeline to predict the effect of genetic factors on skin traits using public data (GWAS catalogs and whole-genome sequencing (WGS) data from the 1000 Genomes Project-1KGP) and in-house Vietnamese data (WGS and genotyping by SNP array). Also, we compared the genetic predispositions of 25 skin-related traits of Vietnamese population to others to acquire population-specific insights regarding skin health. METHODS: Vietnamese cohorts of whole-genome sequencing (WGS) of 1008 healthy individuals for the reference and 96 genotyping samples (which do not have any skin cutaneous issues) by Infinium Asian Screening Array-24 v1.0 BeadChip were employed to predict skin-associated genetic variants of 25 skin-related and micronutrient requirement traits in population analysis and correlation analysis. Simultaneously, we compared the landscape of cutaneous issues of Vietnamese people with other populations by assessing their genetic profiles. RESULTS: The skin-related genetic profile of Vietnamese cohorts was similar at most to East Asian cohorts (JPT: Fst = 0.036, CHB: Fst = 0.031, CHS: Fst = 0.027, CDX: Fst = 0.025) in the population study. In addition, we identified pairs of skin traits at high risk of frequent co-occurrence (such as skin aging and wrinkles (r = 0.45, p = 1.50e-5) or collagen degradation and moisturizing (r = 0.35, p = 1.1e-3)). CONCLUSION: This is the first investigation in Vietnam to explore genetic variants of facial skin. These findings could improve inadequate skin-related genetic diversity in the currently published database.


Asunto(s)
Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Piel , Pueblos del Sudeste Asiático , Humanos , Estudio de Asociación del Genoma Completo , Fenotipo , Vietnam
13.
JOR Spine ; 7(1): e1303, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38222800

RESUMEN

Background: Low back pain is a global health problem that originated mainly from intervertebral disc degeneration (IDD). Autophagy, negatively regulated by the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway, prevents metabolic and degenerative diseases by removing and recycling damaged cellular components. Despite growing evidence that autophagy occurs in the intervertebral disc, the regulation of disc cellular autophagy is still poorly understood. Methods: Annulus fibrosus (rAF) cell cultures derived from healthy female rabbit discs were used to test the effect of autophagy inhibition or activation on disc cell fate and matrix homeostasis. Specifically, different chemical inhibitors including rapamycin, 3-methyladenine, MK-2206, and PP242 were used to modulate activities of different proteins in the PI3K/Akt/mTOR signaling pathway to assess IL-1ß-induced cellular senescence, apoptosis, and matrix homeostasis in rAF cells grown under nutrient-poor culture condition. Results: Rapamycin, an inhibitor of mTOR complex 1 (mTORC1), reduced the phosphorylation of mTOR and its effector p70/S6K in rAF cell cultures. Rapamycin also induced autophagic flux as measured by increased expression of key autophagy markers, including LC3 puncta number, LC3-II expression, and cytoplasmic HMGB1 intensity and decreased p62/SQSTM1 expression. As expected, IL-1ß stimulation promoted rAF cellular senescence, apoptosis, and matrix homeostatic imbalance with enhanced aggrecanolysis and MMP-3 and MMP-13 expression. Rapamycin treatment effectively mitigated IL-1ß-mediated inflammatory stress changes, but these alleviating effects of rapamycin were abrogated by chemical inhibition of Akt and mTOR complex 2 (mTORC2). Conclusions: These findings suggest that rapamycin blunts adverse effects of inflammation on disc cells by inhibiting mTORC1 to induce autophagy through the PI3K/Akt/mTOR pathway that is dependent on Akt and mTORC2 activities. Hence, our findings identify autophagy, rapamycin, and PI3K/Akt/mTOR signaling as potential therapeutic targets for IDD treatment.

14.
JOR Spine ; 7(1): e1286, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38234974

RESUMEN

Background: Intervertebral disc degeneration (IDD) is a leading contributor to low back pain (LBP). Autophagy, strongly activated by hypoxia and nutrient starvation, is a vital intracellular quality control process that removes damaged proteins and organelles to recycle them for cellular biosynthesis and energy production. While well-established as a major driver of many age-related diseases, autophagy dysregulation or deficiency has yet been confirmed to cause IDD. Methods: In vitro, rat nucleus pulposus (NP) cells treated with bafilomycin A1 to inhibit autophagy were assessed for glycosaminoglycan (GAG) content, proteoglycan synthesis, and cell viability. In vivo, a transgenic strain (Col2a1-Cre; Atg7 fl/fl) mice were successfully generated to inhibit autophagy primarily in NP tissues. Col2a1-Cre; Atg7 fl/fl mouse intervertebral discs (IVDs) were evaluated for biomarkers for apoptosis and cellular senescence, aggrecan content, and histological changes up to 12 months of age. Results: Here, we demonstrated inhibition of autophagy by bafilomycin produced IDD features in the rat NP cells, including increased apoptosis and cellular senescence (p21 CIP1) and decreased expression of disc matrix genes Col2a1 and Acan. H&E histologic staining showed significant but modest degenerative changes in NP tissue of Col2a1-Cre; Atg7 fl/fl mice compared to controls at 6 and 12 months of age. Intriguingly, 12-month-old Col2a1-Cre; Atg7 fl/fl mice did not display increased loss of NP proteoglycan. Moreover, markers of apoptosis (cleaved caspase-3, TUNEL), and cellular senescence (p53, p16 INK4a , IL-1ß, TNF-α) were not affected in 12-month-old Col2a1-Cre; Atg7 fl/fl mice compared to controls. However, p21 CIP1and Mmp13 gene expression were upregulated in NP tissue of 12-month-old Col2a1-Cre; Atg7 fl/fl mice compared to controls, suggesting p21 CIP1-mediated cellular senescence resulted from NP-targeted Atg7 knockout might contribute to the observed histological changes. Conclusion: The absence of overt IDD features from disrupting Atg7-mediated macroautophagy in NP tissue implicates other compensatory mechanisms, highlighting additional research needed to elucidate the complex biology of autophagy in regulating age-dependent IDD.

15.
Nucleic Acids Res ; 52(3): e15, 2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38084888

RESUMEN

Whole genome sequencing has increasingly become the essential method for studying the genetic mechanisms of antimicrobial resistance and for surveillance of drug-resistant bacterial pathogens. The majority of bacterial genomes sequenced to date have been sequenced with Illumina sequencing technology, owing to its high-throughput, excellent sequence accuracy, and low cost. However, because of the short-read nature of the technology, these assemblies are fragmented into large numbers of contigs, hindering the obtaining of full information of the genome. We develop Pasa, a graph-based algorithm that utilizes the pangenome graph and the assembly graph information to improve scaffolding quality. By leveraging the population information of the bacteria species, Pasa is able to utilize the linkage information of the gene families of the species to resolve the contig graph of the assembly. We show that our method outperforms the current state of the arts in terms of accuracy, and at the same time, is computationally efficient to be applied to a large number of existing draft assemblies.


Asunto(s)
Algoritmos , Bacterias , Genoma Bacteriano , Bacterias/clasificación , Bacterias/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Análisis de Secuencia de ADN/métodos
16.
Eur Spine J ; 33(3): 892-899, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37046075

RESUMEN

PURPOSE: Lumbar spinal stenosis (LSS) is the most common reason for spinal surgery in patients over the age of 65, and there are few effective non-surgical treatments. Therefore, the development of novel treatment or preventative modalities to decrease overall cost and morbidity associated with LSS is an urgent matter. The cause of LSS is multifactorial; however, a significant contributor is ligamentum flavum hypertrophy (LFH) which causes mechanical compression of the cauda equina or nerve roots. We assessed the role of a novel target, microRNA-29a (miR-29a), in LFH and investigated the potential for using miR-29a as a therapeutic means to combat LSS. METHODS: Ligamentum flavum (LF) tissue was collected from patients undergoing decompressive surgery for LSS and assessed for levels of miR-29a and pro-fibrotic protein expression. LF cell cultures were then transfected with either miR-29a over-expressor (agonist) or inhibitor (antagonist). The effects of over-expression and under-expression of miR-29a on expression of pro-fibrotic proteins was assessed. RESULTS: We demonstrated that LF at stenotic levels had a loss of miR-29a expression. This was associated with greater LF tissue thickness and higher mRNA levels of collagen I and III. We also demonstrated that miR29-a plays a direct role in the regulation of collagen gene expression in ligamentum flavum. Specifically, agents that increase miR-29a may attenuate LFH, while those that decrease miR-29a promote fibrosis and LFH. CONCLUSION: This study demonstrates that miR-29a may potentially be used to treat LFH and provides groundwork to initiate the development of a therapeutic product for LSS.


Asunto(s)
Cauda Equina , MicroARNs , Estenosis Espinal , Humanos , Colágeno Tipo I , Hipertrofia , MicroARNs/genética , Procedimientos Neuroquirúrgicos , Estenosis Espinal/terapia
17.
Sci Rep ; 13(1): 23083, 2023 12 27.
Artículo en Inglés | MEDLINE | ID: mdl-38155188

RESUMEN

Most current genotype imputation methods are reference-based, which posed several challenges to users, such as high computational costs and reference panel inaccessibility. Thus, deep learning models are expected to create reference-free imputation methods performing with higher accuracy and shortening the running time. We proposed a imputation method using recurrent neural networks integrating with an additional discriminator network, namely GRUD. This method was applied to datasets from genotyping chips and Low-Pass Whole Genome Sequencing (LP-WGS) with the reference panels from The 1000 Genomes Project (1KGP) phase 3, the dataset of 4810 Singaporeans (SG10K), and The 1000 Vietnamese Genome Project (VN1K). Our model performed more accurately than other existing methods on multiple datasets, especially with common variants with large minor allele frequency, and shrank running time and memory usage. In summary, these results indicated that GRUD can be implemented in genomic analyses to improve the accuracy and running-time of genotype imputation.


Asunto(s)
Genoma , Polimorfismo de Nucleótido Simple , Humanos , Genotipo , Frecuencia de los Genes , Estudio de Asociación del Genoma Completo/métodos , Técnicas de Genotipaje/métodos
18.
Indian J Microbiol ; 63(3): 386-394, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37781021

RESUMEN

Tomato (Solanum lycopersicum L.) is an important grown vegetable in Vietnam. Bacterial wilt caused by Pseudomonas solanacearum has been considered to be an important disease resulting in a harvest loss up to 90% and significant economic loss to farmers. In this study, two bacteriophages DLDT_So2 and BHDT_So9 specific to P. solanacearum were isolated. Morphological analysis indicated that DLDT_So2 and BHDT_So9 had podovirus morphology and were classified into Autographiviridae family. The latent period and burst size of DLDT_So2 was found to be approximately 120 min and 20.0 ± 2.4 virions per infected cell. Meanwhile, the latent period of BHDT_So9 was 140 min with a burst size of 11.5 ± 2.8 virions per infected cell. Of the 23 bacterial strains tested, the phages infected 7/11 strains of P. solanacearum and none of the other bacteria tested were susceptible to the phages. Stability of the phages at different temperatures, pHs, solvents was also investigated. The genomes of DLDT_So2 and BHDT_So9 are 41,341 bp and 41,296 bp and long with a total GC content of 63%, contains 48 and 46 predicted protein-encoding CDSs. No virulence or antibiotic resistance genes were found in the genomes, suggesting they would be useful biocontrol agents against P. solanacearum. Classification of the phage using average nucleotide identity, phylogenetic analysis was also carried out. The two phages represented new species when they had overall average nucleotide identity of < 95%. This is first report of the isolation and characterization of P. solanacearum-specific phages from tomato farms in Vietnam. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-023-01090-9.

19.
Healthcare (Basel) ; 11(18)2023 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-37761699

RESUMEN

Osteoarthritis (OA) is the degeneration of cartilage in joints that results in bones rubbing against each other; it causes uncomfortable symptoms such as pain, swelling, and stiffness and can lead to disability. It usually occurs in the elderly and causes a large medical burden. The aim of this study is to evaluate the cost-effectiveness between the standard treatment for osteoarthritis and standard treatment with added crystalline glucosamine sulfate at various stages. Markov analysis modeling was applied to evaluate the effect of both adding glucosamine compared to standard treatment from a societal perspective during whole patients' lifetimes. Data input was collected from reviews in previous studies. The outcome was measured in quality-adjusted life years (QALYs), and the Incremental Cost-Effectiveness Ratio (ICER) from a societal perspective was applied with 3% and discounted for all costs and outcomes. One-way analysis via the Tornado diagram was performed to investigate the change in factors in the model. In general, adding glucosamine into the standard treatment proved to be more cost-effective compared to the standard treatment. Particularly, the early-stage addition of glucosamine in the treatment was cost-effective compared to the post-stage addition of glucosamine. The addition of supplementing crystalline glucosamine sulfate to the whole regimen at any stage was cost-effective at the willingness-to-pay (WTP) threshold.

20.
Healthcare (Basel) ; 11(16)2023 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-37628537

RESUMEN

Osteoarthritis (OA) is a chronic condition that most frequently affects older adults. It is currently the most common disability. The cost of treating an aging population places pressure on the healthcare budget. As a result, it is imperative to evaluate medicines' cost-effectiveness and, accordingly, their influence on health resource allocation. Our study aims to summarize the cost and outcome of utilizing glucosamine in OA treatment. Databases like Medline, Cochrane, and Scopus were searched as part of the identification process up until April 2023. Our primary inclusion criteria centered on the economic evaluation of glucosamine in OA treatments, providing an incremental cost-effectiveness ratio (ICER). The Quality of Health Economic Studies (QHES) instrument was applied to grade the quality of the studies. Seven qualified studies that discussed the cost-effectiveness of glucosamine with or without other formulations were selected. All of them demonstrated that glucosamine was cost-effective. There was an increase in quality-adjusted life years (QALYs) when incorporating glucosamine in conventional care. Moreover, patented crystalline glucosamine sulfate (pCGS) was more cost-effective than the other formulations of glucosamine (OFG). Overall, utilizing pCGS was more beneficial than using OFG in terms both of cost and quality of life.

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