Reducing cost in DNA-based data storage by sequence analysis-aided soft information decoding of variable-length reads.

MOTIVATION: DNA-based data storage is one of the most attractive research areas for future archival storage. However, it faces the problems of high writing and reading costs for practical use. There have been many efforts to resolve this problem, but existing schemes are not fully suitable for DNA-based data storage, and more cost reduction is needed. RESULTS: We propose whole encoding and decoding procedures for DNA storage. The encoding procedure consists of a carefully designed single low-density parity-check code as an inter-oligo code, which corrects errors and dropouts efficiently. We apply new clustering and alignment methods that operate on variable-length reads to aid the decoding performance. We use edit distance and quality scores during the sequence analysis-aided decoding procedure, which can discard abnormal reads and utilize high-quality soft information. We store 548.83 KB of an image file in DNA oligos and achieve a writing cost reduction of 7.46% and a significant reading cost reduction of 26.57% and 19.41% compared with the two previous works. AVAILABILITY AND IMPLEMENTATION: Data and codes for all the algorithms proposed in this study are available at: https://github.com/sjpark0905/DNA-LDPC-codes.

Clinical and Economic Impact of Pharmacists' Intervention on Care of Pediatric Hematology and Oncology Patients.

INTRODUCTION: Children with cancer may be one of the most vulnerable groups to drug-related adverse events because they possess characteristics of patients with cancer as well as pediatric patients. To evaluate the clinical and economic impact of pharmacists' intervention on the care of pediatric hematology and oncology patients in the inpatient and outpatient settings of a children's hospital. METHODS: The pharmacist-intervention records from 2017 were retrospectively reviewed. Intervention rate, type of drug-related problems, acceptance rate, and frequently involved drugs in pharmacist interventions were analyzed. One physician and one pharmacist evaluated the clinical significance of each intervention. A cost-benefit analysis was conducted from hospital and patient perspective. The benefit from cost savings by reducing the number of prescribed drugs that are disposed was estimated as the benefit from hospital perspective. The benefit from cost avoidance based on the potential to avoid an adverse drug event (ADE) was estimated as the benefit from patient perspective. The cost of reviewing prescriptions was estimated based on the pharmacists' salary and the time involved. RESULTS: In 2017, 2361 interventions were performed in 381 pediatric patients with cancer. The acceptance rate was 97.2%. More than half of the interventions were regarded as clinically "significant" (58.8%) and "very significant" (14.6%). The cost-benefit of US$28,705 was determined from hospital perspective, with a cost-benefit ratio of 1.45:1. The cost-benefit of US$35,611 was calculated from patient perspective, with a cost-benefit ratio of 1.55:1. CONCLUSIONS: Pharmacists' intervention in the care of hematology and oncology pediatric patients was effective in preventing clinically significant ADEs and had a positive economic impact on the health-care budget from both hospital and patient perspective.

Understanding the biodegradation pathways of azo dyes by immobilized white-rot fungus, Trametes hirsuta D7, using UPLC-PDA-FTICR MS supported by in silico simulations and toxicity assessment.

No biodegradation methods are absolute in the treatment of all textile dyes, which leads to structure-dependent degradation. In this study, biodegradation of three azo dyes, reactive black 5 (RB5), acid blue 113 (AB113), and acid orange 7 (AO7), was investigated using an immobilized fungus, Trametes hirsuta D7. The degraded metabolites were identified using UPLC-PDA-FTICR MS and the biodegradation pathway followed was proposed. RB5 (92%) and AB113 (97%) were effectively degraded, whereas only 30% of AO7 was degraded. Molecular docking simulations were performed to determine the reason behind the poor degradation of AO7. Weak binding affinity, deficiency in H-bonding interactions, and the absence of interactions between the azo (-NN-) group and active residues of the model laccase enzyme were responsible for the low degradation efficiency of AO7. Furthermore, cytotoxicity and genotoxicity assays confirmed that the fungus-treated dye produced non-toxic metabolites. The observations of this study will be useful for understanding and further improving enzymatic dye biodegradation.

Assessment of artificial neural network to identify compositional differences in ultrahigh-resolution mass spectra acquired from coal mine affected soils.

This study assessed the applicability of artificial neural networks (ANNs) as a tool to identify compounds contributing to compositional differences in coal-contaminated soils. An artificial neural network model was constructed from laser desorption ionization ultrahigh-resolution mass spectra obtained from coal contaminated soils. A good correlation (R2 = 1.00 for model and R2 = 0.99 for test) was observed between the measured and predicted values, thus validating the constructed model. To identify chemicals contributing to the coal contents of the soils, the weight values of the constructed model were evaluated. Condensed hydrocarbon and low oxygen containing compounds were found to have larger weight values and hence they were the main contributors to the coal contents of soils. In contrast, compounds identified as lignin did not contribute to the coal contents of soils. These findings were consistent with the conventional knowledge on coal and results from the conventional partial least square method. Therefore, we concluded that the weight interpretation following ANN analysis presented herein can be used to identify compounds that contribute to the compositional differences of natural organic matter (NOM) samples.

An Increase in Medial Joint Space Width After Medial Open-Wedge High Tibial Osteotomy Is Associated With an Increase in the Postoperative Weight-Bearing Line Ratio Rather Than With Cartilage Regeneration: Comparative Analysis of Patients Who Underwent Second-Look Arthroscopic Assessment.

PURPOSE: To investigate relevant factors influencing increases in medial joint space width (JSW) after medial open-wedge high tibial osteotomy (MOWHTO). METHODS: Between January 2010 and December 2018, the electronic medical records of consecutive patients who underwent MOWHTO and subsequent second-look arthroscopic assessment at least 12 months after MOWHTO were retrospectively evaluated. The patients were classified into 2 groups according to changes in the medial JSW of the knee at the time of the second-look operation compared with that at baseline before the initial surgical procedure. Various radiographic parameters, arthroscopic findings, and clinical scores were compared between the groups, and regression analysis was performed to identify factors related to increases in medial JSW. RESULTS: A total of 114 patients were analyzed. In a bivariate analysis, patients who experienced an increase in medial JSW showed a significantly higher postoperative weight-bearing line ratio (WBLR) (P = .008) and a greater proportion of severe preoperative cartilage lesions in the medial compartment of the knee compared with patients with a maintained or reduced medial JSW (P = .035). In terms of clinical scores, patients with an increased medial JSW showed relatively favorable clinical outcomes at the time of the second-look operation. Regression analysis indicated only postoperative WBLR as a relevant factor associated with an increase in medial JSW after MOWHTO (odds ratio, 1.057; P = .01). Additional analysis with patients reclassified according to the postoperative WBLR showed that as the postoperative WBLR increased, the medial JSW increased, without a significant change in the lateral JSW. CONCLUSIONS: An increase in the medial JSW of the knee joint after MOWHTO appears to be associated with an increase in the postoperative WBLR, not with cartilage regeneration. Obtaining adequate correction so that the postoperative WBLR is within 60% to 70% would be desirable in terms of postoperative changes in the medial JSW, as well as clinical outcomes. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Biodegradation and metabolic pathway of anthraquinone dyes by Trametes hirsuta D7 immobilized in light expanded clay aggregate and cytotoxicity assessment.

Biodegradation and metabolic pathways of three anthraquinone dyes, Reactive Blue 4 (RB4), Remazol Brilliant Blue - R (RBBR), and Acid Blue 129 (AB129) by Trametes hirsuta D7 fungus immobilized in light expanded clay aggregate (LECA) were investigated. Morphological characteristics observed with scanning electron microscope (SEM) showed successful immobilization of the fungus in LECA. Based on UV absorbance measurement, immobilized T. hirsuta D7 effectively degraded 90%, 95%, and 96% of RB4, RBBR and AB129, respectively. Metabolites were identified with high-resolution mass spectrometry (HRMS) and degradation pathway of the dyes by T. hirsuta D7 was proposed. Toxicity assay on human dermal fibroblast (HDF) showed that anthraquinone dyes exhibits significant toxicity of 35%, 40%, and 34% reduction of cell viability by RB4, RBBR, and AB129, respectively. Fungal treatment resulted in an abatement of the toxicity and cell viability was increased up to 94%. The data clearly showed the effectiveness of immobilized T. hirsuta D7 in LECA on detoxification of anthraquinone dyes. This study provides potential and fundamental understanding of wastewater treatment using the newly isolated fungus T. hirsuta D7.

Safety assessment of cerium oxide nanoparticles: combined repeated-dose toxicity with reproductive/developmental toxicity screening and biodistribution in rats.

Cerium oxide nanoparticles (CeO2 NPs) are widely used in various commercial applications because of their characteristic properties. People can be easily exposed to CeO2 NPs in real life, but the safety assessment of CeO2 NPs has not been fully investigated. Therefore, in this study, we conducted a combined repeated-dose and reproductive/developmental toxicity screening study (OECD testing guideline 422) to investigate the potential hazards on human health, including reproductive/developmental functions, after repeated daily CeO2 NPs oral gavage administration to both males and females. In addition, tissues from parental animals and their pups were collected to analyze the internal accumulation of cerium. CeO2 NPs were orally administered to Sprague-Dawley rats at doses of 0, 100, 300 and 1000 mg/kg during their pre-mating, mating, gestation and early lactation periods. In the general systemic and reproductive/developmental examinations, no marked toxicities were observed in any in-life and terminal observation parameters in this study. In the biodistribution analysis, cerium was not detected in either parental or pup tissues (blood, liver, lungs and kidneys). Repeated oral exposure of CeO2 NPs did not induce marked toxicities affecting general systemic and reproductive/developmental functions up to the dose level of 1000 mg/kg and the CeO2 NPs were not systemically absorbed in parental animals or their pups. This result could be used in risk assessment for humans, and additional toxicity studies with CeO2 NPs will be necessary considering various physicochemical properties and exposure probabilities of these nanoparticles.

Outcomes of Direct Oral Anticoagulants in Patients With Mitral Stenosis.

BACKGROUND: Patients with mitral stenosis and atrial fibrillation (AF) require anticoagulation for stroke prevention. Thus far, all studies on direct oral anticoagulants (DOACs) have excluded patients with moderate to severe mitral stenosis. OBJECTIVES: The aim of this study was to validate the efficacy of DOACs in patients with mitral stenosis. METHODS: The study population was enrolled from the Health Insurance Review and Assessment Service (HIRA) database in the Republic of Korea, and it included patients who were diagnosed with mitral stenosis and AF and either were prescribed DOACs for off-label use or received conventional treatment with warfarin. The primary efficacy endpoint was ischemic strokes or systemic embolisms, and the safety outcome was intracranial hemorrhage. RESULTS: A total of 2,230 patients (mean age 69.7 ± 10.5 years; 682 [30.6%] males) were included in the present study. Thromboembolic events occurred at a rate of 2.22%/year in the DOAC group, and 4.19%/year in the warfarin group (adjusted hazard ratio for DOAC: 0.28; 95% confidence interval: 0.18 to 0.45). Intracranial hemorrhage occurred in 0.49% of the DOAC group and 0.93% of the warfarin group (adjusted hazard ratio for DOAC: 0.53; 95% confidence interval: 0.22 to 1.26). CONCLUSIONS: In patients with AF accompanied with mitral stenosis, DOAC use is promising and hypothesis generating in preventing thromboembolism. Our results need to be replicated in a randomized trial.

PI3Ka-Akt1-mediated Prdm4 induction in adipose tissue increases energy expenditure, inhibits weight gain, and improves insulin resistance in diet-induced obese mice.

Stimulation of white adipose tissue (WAT) browning is considered as a potential approach to treat obesity and metabolic diseases. Our previous studies have shown that phytochemical butein can stimulate WAT browning through induction of Prdm4 in adipocytes. Here, we investigated the effects of butein on diet-induced obesity and its underlying molecular mechanism. Treatment with butein prevented weight gains and improved metabolic profiles in diet-induced obese mice. Butein treatment groups also displayed higher body temperature, increased energy expenditure, and enhanced expression of thermogenic genes in adipose tissue. Butein also suppressed body weight gains and improved glucose and insulin tolerance in mice housed at thermoneutrality (30 °C). These effects were associated with adipose-selective induction of Prdm4, suggesting the role of Prdm4 in butein-mediated anti-obese effects. To directly assess the in vivo role of Prdm4, we generated aP2-Prdm4 transgenic mouse lines overexpressing Prdm4 in adipose tissues. Adipose-specific transgenic expression of Prdm4 recapitulated the butein's actions in stimulating energy expenditure, cold tolerance, and thermogenic gene expression, resulting in prevention of obesity and improvement of metabolism. Mechanistically, direct inhibition of PI3Kα activity followed by selective suppression of its downstream Akt1 mirrored butein's effect on Ucp1 expression and oxygen consumption. In addition, effects of butein were completely abolished in Akt1 KO mouse embryonic fibroblasts. Together, these studies demonstrate the role of butein in obesity and metabolic diseases, further highlighting that adipose PI3Kα-Akt1-Prdm4 axis is a regulator of energy expenditure.

Computational model-based probabilistic analysis of in vivo material properties for ligament stiffness using the laxity test and computed tomography.

The objective of this paper was to evaluate in vivo material properties in order to address technical aspects of computational modeling of ligaments in the tibiofemoral joint using a probabilistic method. The laxity test was applied to the anterior-posterior drawer under 30° and 90° of flexion with a series of stress radiographs, a Telos device, and computed tomography. Ligament stiffness was investigated using sensitivity analysis based on the Monte-Carlo method with a subject-specific finite element model generated from in vivo computed tomography and magnetic resonance imaging data, subjected to laxity test conditions. The material properties of ligament stiffness and initial ligament strain in a subject-specific finite element model were optimized to minimize the differences between the movements of the tibia and femur in the finite element model and the computed tomography images in the laxity test. The posterior cruciate ligament was the most significant factor in flexion and posterior drawer, while the anterior cruciate ligament primarily was the most significant factor for the anterior drawer. The optimized material properties model predictions in simulation and the laxity test were more accurate than predictions based on the initial material properties in subject-specific computed tomography measurement. Thus, this study establishes a standard for future designs in allograft, xenograft, and artificial ligaments for anterior cruciate ligament and posterior cruciate ligament injuries.