Interval-valued analysis for discriminative gene selection and tissue sample classification using microarray data

AbstractAn important application of gene expression data is to classify samples in a variety of diagnostic fields. However, high dimensionality and a small number of noisy samples pose significant challenges to existing classification methods. Focused on the problems of overfitting and sensitivity to noise of the dataset in the classification of microarray data, we propose an interval-valued analysis method based on a rough set technique to select discriminative genes and to use these genes to classify tissue samples of microarray data. We first select a small subset of genes based on interval-valued rough set by considering the preference-ordered domains of the gene expression data, and then classify test samples into certain classes with a term of similar degree. Experiments show that the proposed method is able to reach high prediction accuracies with a small number of selected genes and its performance is robust to noise

Coexistence of Histologically Confirmed Hashimoto's Thyroiditis with Different Stages of Papillary Thyroid Carcinoma in a Consecutive Chinese Cohort

Purpose. To determine the relationship between Hashimoto's thyroiditis (HT) and all stages of papillary thyroid carcinoma (PTC) with or without local lymph node metastasis (LNM). Methods:. We conducted a retrospective study of thyroidectomies from 2008–2013 in First Affiliated Hospital of Nanjing Medical University. We categorized patients according to the presence of histopathologically proven HT. The prevalence of mPTC (maximum diameter ≤ 10 mm) and crPTC (clinical relevant PTC) and local LNM rates were compared. Results:. We evaluated 6,432 consecutive thyroidectomies. In total, 1,328 specimens were confirmed as HT. The prevalence of PTC in this HT cohort was 43.8%, significantly higher than non-HT group. After adjustment of gender and age, the prevalence of PTC was still higher in HT group. HT was a risk factor for PTC in multivariate analysis with odds ratio 2.725 (95% CI, 2.390–3.109) (P < 0.001). However, no correlation was found between HT and LNM of PTC. Conclusion:. HT was associated with an increased prevalence of all stages of PTC, independent of tumor size, gender, and age. In contrast, locally advanced disease defined by LNM was unrelated to HT. These data suggest an association of HT with low risk PTC and a potential protective immunologic effect from further disease progression

Xenotime-type high-entropy (Dy1/7Ho1/7Er1/7Tm1/7Yb1/7Lu1/7Y1/7)PO4: A promising thermal/environmental barrier coating material for SiCf/SiC ceramic matrix composites

Rare-earth phosphates (REPO4) are regarded as one of the promising thermal/environmental barrier coating (T/EBC) materials for SiCf/SiC ceramic matrix composites (SiC-CMCs) owing to their excellent resistance to water vapor and CaO–MgO–Al2O3–SiO2 (CMAS). Nevertheless, a relatively high thermal conductivity (κ) of the REPO4 becomes the bottleneck for their practical applications. In this work, novel xenotime-type high-entropy (Dy1/7Ho1/7Er1/7Tm1/7Yb1/7Lu1/7Y1/7)PO4 (HE (7RE1/7)PO4) has been designed and synthesized for the first time to solve this issue. HE (7RE1/7)PO4 with a homogeneous rare-earth element distribution exhibits high thermal stability up to 1750 ℃ and good chemical compatibility with SiO2 up to 1400 ℃. In addition, the thermal expansion coefficient (TEC) of HE (7RE1/7)PO4 (5.96×10−6 ℃−1 from room temperature (RT) to 900 ℃) is close to that of the SiC-CMCs. What is more, the thermal conductivities of HE (7RE1/7)PO4 (from 4.38 W·m−1·K−1 at 100 ℃ to 2.25 W·m−1·K−1 at 1300 ℃) are significantly decreased compared to those of single-component REPO4 with the minimum value ranging from 9.90 to 4.76 W·m−1·K−1. These results suggest that HE (7RE1/7)PO4 has the potential to be applied as the T/EBC materials for the SiC-CMCs in the future

Analysis of gut microbiotal diversity in healthy young adults in Sunan County, Gansu Province, China

ObjectiveTo examine gut microbiotal diversity in the Han Chinese and Yugur populations of Sunan County, Gansu Province, living in the same environmental conditions, and to analyze possible causes of differences in diversity.MethodsWe selected 28 people, ages 18–45 years old, all of whom were third-generation pure Yugur or Han Chinese from Sunan County. Fresh fecal samples were collected, and total bacterial deoxyribonucleic acid (DNA) was extracted. We performed 16S ribosomal ribonucleic acid (16S rRNA) high-throughput sequencing (HTS) and bioinformatics to study the relationships among between gut microbiota structure, genetics, and dietary habits in Yugur and Han Chinese subjects.ResultsWe found 350 differential operational taxonomic units (OTUs) in Han Chinese and Yugur gut microbiota, proving that gut microbiota differed between the two populations. That were less abundant among Yugurs than Han Chinese were Prevotella_9 and Alloprevotella. That were more abundant among Yugurs than Han Chinese were Anaerostipes and Christensenellaceae_R-7_group. And they were significantly associated with a high-calorie diet In addition. we found differences in predicted gut microbiota structural functions (The main functions were metabolic and genetic information) between the two populations.ConclusionYugur subjects demonstrated differences in gut microbiotal structure from Han Chinese subjects, and this difference influenced by dietary and may be influenced by genetic influences. This finding will provide a fundamental basis for further study of the relationships among gut microbiota, dietary factors, and disease in Sunan County

Artificial intelligence-aided rapid and accurate identification of clinical fungal infections by single-cell Raman spectroscopy

Integrating artificial intelligence and new diagnostic platforms into routine clinical microbiology laboratory procedures has grown increasingly intriguing, holding promises of reducing turnaround time and cost and maximizing efficiency. At least one billion people are suffering from fungal infections, leading to over 1.6 million mortality every year. Despite the increasing demand for fungal diagnosis, current approaches suffer from manual bias, long cultivation time (from days to months), and low sensitivity (only 50% produce positive fungal cultures). Delayed and inaccurate treatments consequently lead to higher hospital costs, mobility and mortality rates. Here, we developed single-cell Raman spectroscopy and artificial intelligence to achieve rapid identification of infectious fungi. The classification between fungi and bacteria infections was initially achieved with 100% sensitivity and specificity using single-cell Raman spectra (SCRS). Then, we constructed a Raman dataset from clinical fungal isolates obtained from 94 patients, consisting of 115,129 SCRS. By training a classification model with an optimized clinical feedback loop, just 5 cells per patient (acquisition time 2 s per cell) made the most accurate classification. This protocol has achieved 100% accuracies for fungal identification at the species level. This protocol was transformed to assessing clinical samples of urinary tract infection, obtaining the correct diagnosis from raw sample-to-result within 1 h

Co‐evolutionary adaptations of Acinetobacter baumannii and a clinical carbapenemase‐encoding plasmid during carbapenem exposure

Abstract: OXA‐23 is the predominant carbapenemase in carbapenem‐resistant Acinetobacter baumannii. The co‐evolutionary dynamics of A. baumannii and OXA‐23‐encoding plasmids are poorly understood. Here, we transformed A. baumannii ATCC 17978 with pAZJ221, a blaOXA−23‐containing plasmid from clinical A. baumannii isolate A221, and subjected the transformant to experimental evolution in the presence of a sub‐inhibitory concentration of imipenem for nearly 400 generations. We used population sequencing to track genetic changes at six time points and evaluated phenotypic changes. Increased fitness of evolving populations, temporary duplication of blaOXA−23 in pAZJ221, interfering allele dynamics, and chromosomal locus‐level parallelism were observed. To characterize genotype‐to‐phenotype associations, we focused on six mutations in parallel targets predicted to affect small RNAs and a cyclic dimeric (3′ → 5′) GMP‐metabolizing protein. Six isogenic mutants with or without pAZJ221 were engineered to test for the effects of these mutations on fitness costs and plasmid kinetics, and the evolved plasmid containing two copies of blaOXA−23 was transferred to ancestral ATCC 17978. Five of the six mutations contributed to improved fitness in the presence of pAZJ221 under imipenem pressure, and all but one of them impaired plasmid conjugation ability. The duplication of blaOXA−23 increased host fitness under carbapenem pressure but imposed a burden on the host in antibiotic‐free media relative to the ancestral pAZJ221. Overall, our study provides a framework for the co‐evolution of A. baumannii and a clinical blaOXA−23‐containing plasmid in the presence of imipenem, involving early blaOXA−23 duplication followed by chromosomal adaptations that improved the fitness of plasmid‐carrying cells

Pharmacokinetics/pharmacodynamics of polymyxin B in patients with bloodstream infection caused by carbapenem-resistant Klebsiella pneumoniae

Introduction: Polymyxin B is a last-line therapy for carbapenem-resistant microorganisms. However, a lack of clinical pharmacokinetic/pharmacodynamic (PK/PD) data has substantially hindered dose optimization and breakpoint setting.Methods: A prospective, multi-center clinical trial was undertaken with polymyxin B [2.5 mg/kg loading dose (3-h infusion), 1.25 mg/kg/12 h maintenance dose (2-h infusion)] for treatment of carbapenem-resistant K. pneumoniae (CRKP) bloodstream infections (BSI). Safety, clinical and microbiological efficacy were evaluated. A validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was applied to determine the concentrations of polymyxin B in blood samples. Population pharmacokinetic (PK) modeling and Monte Carlo simulations were conducted to examine the susceptibility breakpoint for polymyxin B against BSI caused by CRKP.Results: Nine patients were enrolled and evaluated for safety. Neurotoxicity (5/9), nephrotoxicity (5/9), and hyperpigmentation (1/9) were recorded. Blood cultures were negative within 3 days of commencing therapy in all 8 patients evaluated for microbiological efficacy, and clinical cure or improvement occurred in 6 of 8 patients. Cmax and Cmin following the loading dose were 5.53 ± 1.80 and 1.62 ± 0.41 mg/L, respectively. With maintenance dosing, AUCss,24 h was 79.6 ± 25.0 mg h/L and Css,avg 3.35 ± 1.06 mg/L. Monte Carlo simulations indicated that a 1 mg/kg/12-hourly maintenance dose could achieve &gt;90% probability of target attainment (PTA) for isolates with minimum inhibitory concentration (MIC) ≤1 mg/L. PTA dropped substantially for MICs ≥2 mg/L, even with a maximally recommended daily dose of 1.5 mg/kg/12-hourly.Conclusion: This is the first clinical PK/PD study evaluating polymyxin B for BSI. These results will assist to optimize polymyxin B therapy and establish its breakpoints for CRKP BSI