Plasma cell segmentation is the first stage of a computer assisted automated diagnostic tool for multiple myeloma (MM). Owing to large variability in biological cell types, a method for one cell type ...cannot be applied directly on the other cell types. In this paper, we present PCSeg Tool for plasma cell segmentation from microscopic medical images. These images were captured from bone marrow aspirate slides of patients with MM. PCSeg has a robust pipeline consisting of a pre-processing step, the proposed modified multiphase level set method followed by post-processing steps including the watershed and circular Hough transform to segment clusters of cells of interest and to remove unwanted cells. Our modified level set method utilizes prior information about the probability densities of regions of interest (ROIs) in the color spaces and provides a solution to the minimal-partition problem to segment ROIs in one of the level sets of a two-phase level set formulation. PCSeg tool is tested on a number of microscopic images and provides good segmentation results on single cells as well as efficient segmentation of plasma cell clusters.
Phosphates are ubiquitous molecules that enable critical intracellular biochemical reactions. Therefore, cells have elaborate responses to phosphate limitation. Our understanding of long-term ...transcriptional responses to phosphate limitation is extensive. Contrastingly, a systems-level perspective presenting unifying biochemical concepts to interpret how phosphate balance is critically coupled to (and controls) metabolic information flow is missing. To conceptualize such processes, utilizing yeast metabolic networks we categorize phosphates utilized in metabolism into cycles, sources and sinks. Through this, we identify metabolic reactions leading to putative phosphate sources or sinks. With this conceptualization, we illustrate how mass action driven flux towards sources and sinks enable cells to manage phosphate availability during transient/immediate phosphate limitations. We thereby identify how intracellular phosphate availability will predictably alter specific nodes in carbon metabolism, and determine signature cellular metabolic states. Finally, we identify a need to understand intracellular phosphate pools, in order to address mechanisms of phosphate regulation and restoration.
Abstract
There is considerable evidence that the superconducting state of Sr
2
RuO
4
breaks time reversal symmetry. In the experiments showing time reversal symmetry breaking, its onset temperature,
...T
TRSB
, is generally found to match the critical temperature,
T
c
, within resolution. In combination with evidence for even parity, this result has led to consideration of a
d
x
z
±
i
d
y
z
order parameter. The degeneracy of the two components of this order parameter is protected by symmetry, yielding
T
TRSB
=
T
c
, but it has a hard-to-explain horizontal line node at
k
z
= 0. Therefore,
s
±
i
d
and
d
±
i
g
order parameters are also under consideration. These avoid the horizontal line node, but require tuning to obtain
T
TRSB
≈
T
c
. To obtain evidence distinguishing these two possible scenarios (of symmetry-protected versus accidental degeneracy), we employ zero-field muon spin rotation/relaxation to study pure Sr
2
RuO
4
under hydrostatic pressure, and Sr
1.98
La
0.02
RuO
4
at zero pressure. Both hydrostatic pressure and La substitution alter
T
c
without lifting the tetragonal lattice symmetry, so if the degeneracy is symmetry-protected,
T
TRSB
should track changes in
T
c
, while if it is accidental, these transition temperatures should generally separate. We observe
T
TRSB
to track
T
c
, supporting the hypothesis of
d
x
z
±
i
d
y
z
order.
Purpose To conduct a cost-benefit analysis of AcrySof IQ PanOptix trifocal intraocular lens (TFNT00 IOL) versus AcrySof monofocal IOL (SN60AT) from the patient perspective in the United States (US). ...Methods A de novo Markov model was developed to estimate the mean total lifetime patient costs and vision-related quality of life (measured as quality adjusted life-years (QALYs)) with each intervention (TFNT00 and SN60AT) and the incremental differences between these two treatments. The resulting incremental quality of life gain was mapped to the US patient willingness to pay threshold of $50,000 per QALY gain to estimate the lifetime net monetary value, measured as the net monetary benefit of TFNT00 IOL. Model inputs (transition probabilities, costs, discount rate, utilities, and event rates) were derived from the FDA IDE study (NCT03280108), published literature, clinical experience, and other relevant sources. Results Bilateral cataract surgery with implantation of the advanced technology IOL (AT-IOL) TFNT00 provides improved vision-related quality of life (QALY gain of 0.67) at an incremental lifetime cost of $2,783 compared to monofocal IOL. This incremental QALY gain translated into a lifetime net monetary benefit of $30,941 at the patient willingness to pay threshold of $50,000/QALY gain. Results were most sensitive to disutility due to wearing glasses, patient out of pocket costs for bilateral AT-IOL procedure, and post-operative spectacle dependence rates. Conclusions AcrySof IQ PanOptix IOL provides greater improvement in vision related quality of life compared to no presbyopia correction with a monofocal IOL. This study shows PanOptix is a cost-beneficial treatment strategy for patients willing to pay out of pocket for cataract surgery.
This paper reports the dielectric behaviour and electrical conduction properties of Y6-xBa4Ybx(SiO4)6O2 (YBaSiO: xYb) compounds. The Scanning Electron Microscopy (SEM) was utilized to obtain the ...surface microstructure of the compound. The micrographs showed both the circular and elongated shape of grains and their random distribution. The Fourier Transform Infrared Spectroscopy (FTIR) was used to confirm the presence of bond formations in the compounds. From the spectra, it was observed that the peaks at 690 cm−1 and a band from 850 cm−1 to 998 cm−1 are due to the stretching frequency of Y-O molecules and Si-O molecules, respectively. The peak centred at 1464 cm−1 is of vibration modes of Ba2+ions. These peaks confirmed the formation of oxy-apatite compounds. Both the dielectric permittivity and dielectric loss, decreases with increasing values of frequency due to reduction in the polarization effects on the higher side of frequency. This is because the dipole orientation lags with the rapidly reversing alternating current (ac) field. The value of dielectric loss was found to range between, 0 – 3.5 in frequency ∼ 100 Hz and 0 – 0.5 in frequency ∼ 100,000 Hz, up to temperature 500 °C. The impedance value decreases and hence a. c. conductivity increases, at higher frequencies. The increment in ac values followed the universal power law. The Nyquist plot showed that the area under the curves reduces and hence indicates negative temperature coefficient of resistance i.e., NTCR behaviour of compounds. The obtained results suggest the utilization of compound in electrical devices as power loss component, solid oxide fuel cells, and capacitors etc.
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The circulating cell-free nucleic acids (ccfNAs) consist of a heterogenous cocktail of both single (ssNA) and double-stranded (dsNA) nucleic acids. These ccfNAs are secreted into the blood ...circulation by both healthy and malignant cells
various mechanisms including apoptosis, necrosis, and active secretion. The major source of ccfNAs are the cells of hematopoietic system under healthy conditions. These ccfNAs include fragmented circulating cell free DNA (ccfDNA), coding or messenger RNA (mRNA), long non-coding RNA (lncRNA), microRNA (miRNA), and mitochondrial DNA/RNA (mtDNA and mtRNA), that serve as prospective biomarkers in assessment of various clinical conditions. For, e.g., free fetal DNA and RNA migrate into the maternal plasma, whereas circulating tumor DNA (ctDNA) has clinical relevance in diagnostic, prognostic, therapeutic targeting, and disease progression monitoring to improve precision medicine in cancer. The epigenetic modifications of ccfDNA as well as circulating cell-free RNA (ccfRNA) such as miRNA and lncRNA show disease-related variations and hold potential as epigenetic biomarkers. The messenger RNA present in the circulation or the circulating cell free mRNA (ccf-mRNA) and long non-coding RNA (ccf-lncRNA) have gradually become substantial in liquid biopsy by acting as effective biomarkers to assess various aspects of disease diagnosis and prognosis. Conversely, the simultaneous characterization of coding and non-coding RNAs in human biofluids still poses a significant hurdle. Moreover, a comprehensive assessment of ccfRNA that may reflect the tumor microenvironment is being explored. In this review, we focus on the novel approaches for exploring ccfDNA and ccfRNAs, specifically ccf-mRNA as biomarkers in clinical diagnosis and prognosis of cancer. Integrating the detection of circulating tumor DNA (ctDNA) for cancer genotyping in conjunction with ccfRNA both quantitatively and qualitatively, may potentially hold immense promise towards precision medicine. The current challenges and future directions in deciphering the complexity of cancer networks based on the dynamic state of ccfNAs will be discussed.
Oral cancer is one of the highly prevalent cancers worldwide and a leading cause of mortality in certain regions like South-Central Asia. It is a major public health problem. Late diagnosis, high ...mortality rates and morbidity are characteristics of the disease worldwide. For control of oral cancer an idea of the coverage of the same in the various regions is necessary. The estimated incidence, mortality and 5-year survival due to lip, oral cavity cancer in world is 3, 00, 373(2.1%), 1, 45, 328(1.8%) and 7, 02, 149(2.2%) respectively according to data of GLOBOCAN 2012. A changing trend in incidence and prevalence of oral cancer has been observed with more women and youngsters being affected by oral cancer.
In vitro drug release testing is an important quality control tool for formulation development. However, the literature has evidence that poly-lactide-co-glycolide (PLGA)-based formulations show a ...slower in vitro drug release than a real in vivo drug release. Much longer in vitro drug release profiles may not be reflective of real in vivo performances and may significantly affect the timeline for a formulation development. The objective of this study was to develop a surfactant mediated accelerated in vitro drug release method for the PLGA nanoparticles (NPs) of a novel chemotherapeutic agent AC1LPSZG, a model drug with a poor solubility. The Sotax USP apparatus 4 was used to test in vitro drug release in a phosphate buffer with a pH value of 6.8. The sink conditions were improved using surfactants in the order of sodium lauryl sulfate (SLS) < Tween 80 < cetyltrimethylammonium bromide (CTAB). The dissolution efficiency (DE) and area under the dissolution curve (AUC) were increased three-fold when increasing the CTAB concentration in the phosphate buffer (pH 6.8). Similar Weibull release kinetics and good linear correlations (R2~0.99) indicated a good correlation between the real-time in vitro release profile in the phosphate buffer (pH 6.8) and accelerated release profiles in the optimized medium. This newly developed accelerated and discriminatory in vitro test can be used as a quality control tool to identify critical formulation and process parameters to ensure a batch-to-batch uniformity. It may also serve as a surrogate for bioequivalence studies if a predictive in vitro in vivo correlation (IVIVC) is obtained. The results of this study are limited to AC1LPSZG NPs, but a similar consideration can be extended to other PLGA-based NPs of drugs with similar properties and solubility profiles.
Gene expression data generated from microarray technology is often analyzed for disease diagnostics and treatment. However, this data suffers with missing values that may lead to inaccurate findings. ...Since data capture is expensive, time consuming, and is required to be collected from subjects, it is worthwhile to recover missing values instead of re-collecting the data. In this paper, a novel but simple method, namely, DSNN (Doubly Sparse DCT domain with Nuclear Norm minimization) has been proposed for imputing missing values in microarray data. Extensive experiments including pathway enrichment have been carried out on four blood cancer dataset to validate the method as well as to establish the significance of imputation.
A new method, namely, DSNN, was proposed for missing value imputation on gene expression data. Method was validated on four dataset, CLL, AML, MM (Spanish data), and MM (Indian data). All the dataset were downloaded from GEO repository. Missing values were introduced in the original data from 10 to 90% in steps of 10% because method validation requires ground truth. Quantitative results on normalized mean square error (NMSE) between the ground truth and imputed data were computed. To further validate and establish the significance of the proposed imputation method, two experiments were carried out on the data imputed with the proposed method, data imputed with the state-of-art methods, and data with missing values. In the first experiment, classification of normal vs. cancer subjects was carried out. In the second experiment, biological significance of imputation was ascertained by identifying top candidate tumor drivers using the existing state-of-the-art SPARROW algorithm, followed by gene list enrichment analysis on top candidate drivers.
Quantitative NMSE results of the DSNN method were compared with three state-of-the-art imputation methods. DSNN method was observed to perform better compared to these other methods both at high as well as low observable data. Experiment-1 demonstrated superior results on classification with imputation compared to that performed on missing data matrix as well as compared to classification on imputed data with existing methods. In experiment-2, cancer affected pathways were discovered with higher significance in the data imputed with the proposed method compared to those discovered with the missing data matrix.
Missing value problem in microarray data is a serious problem and can adversely influence downstream analysis. A novel method, namely, DSNN is proposed for missing value imputation. The method is validated quantitatively on the application of classification and biologically by performing pathway enrichment analysis.
At nanoscale, man-made materials may show unique properties that differ from bulk and dissolved counterparts. The unique properties of engineered nanomaterials not only impart critical advantages but ...also confer toxicity because of their unwanted interactions with different biological compartments and cellular processes. In this review, we discuss various entry routes of nanomaterials in the human body, their applications in daily life, and the mechanisms underlying their toxicity. We further explore the passage of nanomaterials into air, water, and soil ecosystems, resulting in diverse environmental impacts. Briefly, we probe the available strategies for risk assessment and risk management to assist in reducing the occupational risks of potentially hazardous engineered nanomaterials including the control banding (CB) approach. Moreover, we substantiate the need for uniform guidelines for systematic analysis of nanomaterial toxicity, in silico toxicological investigations, and obligation to ensure the safe disposal of nanowaste to reduce or eliminate untoward environmental and health impacts. At the end, we scrutinize global regulatory trends, hurdles, and efforts to develop better regulatory sciences in the field of nanomedicines.
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