Two-stage deep learning architecture for pneumonia detection and its diagnosis in chest radiographs

Approximately two million pediatric deaths occur every year due to Pneumonia. Detection and diagnosis of Pneumonia plays an important role in reducing these deaths. Chest radiography is one of the most commonly used modalities to detect pneumonia. In this paper, we propose a novel two-stage deep learning architecture to detect pneumonia and classify its type in chest radiographs. This architecture contains one network to classify images as either normal or pneumonic, and another deep learning network to classify the type as either bacterial or viral. In this paper, we study and compare the performance of various stage one networks such as AlexNet, ResNet, VGG16 and Inception-v3 for detection of pneumonia. For these networks, we employ transfer learning to exploit the wealth of information available from prior training. For the second stage, we find that transfer learning with these same networks tends to overfit the data. For this reason we propose a simpler CNN architecture for classification of pneumonic chest radiographs and show that it overcomes the overfitting problem. We further enhance the performance of our system in a novel way by incorporating lung segmentation using a U-Net architecture. We make use of a publicly available dataset comprising 5856 images (1583 - Normal, 4273 - Pneumonic). Among the pneumonia patients, 2780 patients are identified as bacteria type and the rest belongs to virus category. We test our proposed algorithm(s) on a set of 624 images and we achieve an area under the receiver operating characteristic curve of 0.996 for pneumonia detection. We also achieve an accuracy of 97.8% for classification of pneumonic chest radiographs thereby setting a new benchmark for both detection and diagnosis. We believe the proposed two-stage classification of chest radiographs for pneumonia detection and its diagnosis would enhance the workflow of radiologists

Novel 2,5-disubstituted-1,3,4-oxadiazole derivatives induce apoptosis in HepG2 cells through p53 mediated intrinsic pathway

AbstractA series of novel 1,3,4-oxadiazole derivatives (OSD, OCOD, ONOD, OPD, COD, PMOD, and PCOD) were synthesized and characterized. Their structures were confirmed on the basis of IR, NMR and mass spectroscopy and molecular weights were found in the range 300–325g/mol. Cancerous cell lines (MCF-7, HepG2) and non-cancerous cell lines (Chang liver cells) were treated with these compounds for 48h, which caused dose dependent decrease in the cell viability. From the seven derivatives, OSD was found to be most potent with IC50 value close to 50μM on all tested cell lines. Hence, this compound was selected for mechanistic study on HepG2 cell lines. Fluorescent cell staining and DNA fragmentation study of 50μM OSD on HepG2 cells, showed events marked by apoptosis such as nuclear fragmentation, cytoplasm shrinkage and DNA damage. Further, the cells with same treatment were quantified for apoptosis using annexin V-PI flow cytometric technique. The percentage of apoptotic cells was significantly higher (p<0.05) after OSD treatment compared to control cells. OSD induced a significant increase (p<0.05) in the expression of the tumor suppressor p53 in HepG2 cells. The constitutive expression of anti-apoptotic protein Bcl-2 significantly decreased (p<0.05) after treatment, while the expression of proapoptotic protein Bax significantly increased (p<0.05). The change in Bax to Bcl-2 ratio suggested involvement of Bcl-2 family in induction of apoptosis. Furthermore, the levels of caspase-9 and caspase-3 were significantly (p<0.05) up regulated in HepG2 cells after OSD treatment. The data suggest that 1,3,4-oxadiazole derivatives induce apoptosis mediated by intrinsic pathway of apoptosis. The findings strengthen the potential of the 1,3,4-oxadiazole scaffold OSD, as an agent with chemotherapeutic and cytostatic activity in human hepatocellular carcinoma in vitro

Colorimetric method of Ziprasidone In bulk and in pharmaceutical dosage forms

ABSTRACT A new simple, sensitive and precise visible spectrophotometric method has been developed for the determination of Ziprasidone in bulk and in pharmaceutical formulations. This method is based on the hydrolysis of Ziprasidone, followed by diazotization and coupling with N-(1-naphthyl) ethylene diamine dihydrochloride to form an azo dye which was estimated at an absorption maximum of 540nm (pink color). This method has the linearity in the concentration range of 2-10µg/ml. This method is statistically evaluated for efficacy

KDM6A Regulates Cell Plasticity and Pancreatic Cancer Progression by Non-Canonical Activin Pathway

BACKGROUND & AIMS: Inactivating mutations of KDM6A, a histone demethylase, were frequently found in pancreatic ductal adenocarcinoma (PDAC). We investigated the role of KDM6A in PDAC development. METHODS: We performed a pancreatic tissue microarray analysis of KDM6A protein levels. We used human PDAC cell lines for KDM6A knockout and knockdown experiments. We performed Bru-seq analysis to elucidate the effects of KDM6A loss on global transcription. We performed studies with Ptf1a(Cre); LSL-Kras(G12D); Trp53(R172H/+); Kdm6a(fl/fl or fl/Y), Ptf1a(Cre); Kdm6a(fl/fl or fl/Y), and orthotopic xenograft mice to investigate the impacts of Kdm6a deficiency on pancreatic tumorigenesis and pancreatitis. RESULTS: Loss of KDM6A was associated with metastasis in PDAC patients. Bru-seq analysis revealed upregulation of the epithelial-mesenchymal transition pathway in PDAC cells deficient of KDM6A. Loss of KDM6A promoted mesenchymal morphology, migration, and invasion in PDAC cells in vitro. Mechanistically, activin A and subsequent p38 activation likely mediated the role of KDM6A loss. Inhibiting either activin A or p38 reversed the effect. Pancreas-specific Kdm6a-knockout mice pancreata demonstrated accelerated PDAC progression, developed a more aggressive undifferentiated type PDAC, and increased metastases in the background of Kras and p53 mutations. Kdm6a-deficient pancreata in a pancreatitis model had a delayed recovery with increased PDAC precursor lesions compared to wild-type pancreata. CONCLUSIONS: Loss of KDM6A accelerates PDAC progression and metastasis, most likely by a non-canonical p38-dependant activin A pathway. KDM6A also promotes pancreatic tissue recovery from pancreatitis. Activin A might be utilized as a therapeutic target for KDM6A-deficient PDACs

Screening methods for obstructive sleep apnoea in severely obese pregnant women

Obstructive sleep apnoea (OSA) is an often-overlooked diagnosis, more prevalent in the obese population. Screening method accuracy, uptake and hence diagnosis is variable. There is limited data available regarding the obese pregnant population; however, many studies highlight potential risks of apnoeic episodes to mother and foetus, including hypertension, diabetes and preeclampsia. A total of 162 women with a body mass index (BMI) ≥ 35 were recruited from a tertiary referral hospital in the northwest of England. They were invited to attend three research antenatal clinics, completing an Epworth Sleepiness Scale (ESS) questionnaire at each visit. A monitor measuring the apnoea hypopnoea index (AHI) was offered at the second visit. Data taken from consent forms, hospital notes and hospital computer records were collated and anonymized prior to statistical analysis. A total of 12.1% of women had an ESS score of >10, suggesting possible OSA. Rates increased throughout pregnancy, although unfortunately, the attrition rate was high; 29.0% of women used the RUSleeping (RUS) meter, and only one (2.1%) met pre-specified criteria for OSA (AHI ≥ 15). This individual had OSA categorized as severe and underwent investigations for preeclampsia, eventually delivering by emergency caesarean section due to foetal distress. The accuracy of the ESS questionnaire, particularly the RUS monitor, to screen for OSA in the pregnant population remains unclear. Further research on a larger sample size using more user-friendly technology to confidently measure AHI would be beneficial. There are currently no guidelines regarding screening for OSA in the obese pregnant population, yet risks to both mother and foetus are well researched

Critical weather limits for paddy rice under diverse ecosystems of India

Rice yields are largely influenced by variability in weather. Here, we demonstrate the effect of weather variables viz., maximum and minimum temperatures, rainfall, morning and evening relative humidity, bright sunshine hours on the yield of rice cv. Swarna, grown across five rice ecologies of India through field experiments during kharif (wet) season (Jun-Sept.). Critical thresholds of weather elements were identified for achieving above average, average and below average yield for each ecology. The investigation could determine how different weather elements individually and collectively affect rice yield in different rice ecosystems of India. While a sudden increase in minimum temperature by 8-10 °C (&gt; 30 °C) during reproductive period resulted in 40-50 per cent yield reduction at Mohanpur, a sudden decrease (&lt; 20 °C) caused yield decline at Dapoli. The higher yields may be attributed to a significant difference in bright sunshine hours between reproductive phases of above-average and below-average yield years (ranging from 2.8 to 7.8 hours during P5 stages and 1.7 to 5.1 during P4 stages). Rice cultivar Swarna performed differently at various sowing dates in a location as well as across locations (6650 kg ha-1 at Dapoli to 1101 kg ha-1 at Samastipur). It was also found that across all locations, the above average yield could be associated with higher range of maximum temperature compared to that of below average yield. Principal component analysis explained 77 per cent of cumulative variance among the variables at first growth stage, whereas 70 per cent at second growth stage followed by 74 per cent and 66 per cent at subsequent growth stages. We found that coastal locations, in contrast to inland ones, could maximize the yield potential of the cultivar Swarna, due to the longer duration of days between panicle initiation to physiological maturity. We anticipate that the location-specific thresholds of weather factors will encourage rice production techniques that are climate resilient

A defect of sphingolipid metabolism modifies the properties of normal appearing white matter in multiple sclerosis

Maintaining the appropriate complement and content of lipids in cellular membranes is critical for normal neural function. Accumulating evidence suggests that even subtle perturbations in the lipid content of neurons and myelin can disrupt their function and may contribute to myelin and axonal degradation. In this study, we determined the composition and quantified the content of lipids and sterols in normal appearing white matter (NAWM) and normal appearing grey matter (NAGM) from control and multiple sclerosis brain tissues by electrospray ionization tandem mass spectrometry. Our results suggest that in active-multiple sclerosis, there is a shift in the lipid composition of NAWM and NAGM to a higher phospholipid and lower sphingolipid content. We found that this disturbance in lipid composition was reduced in NAGM but not in NAWM of inactive-multiple sclerosis. The pattern of disturbance in lipid composition suggests a metabolic defect that causes sphingolipids to be shuttled to phospholipid production. Modelling the biophysical consequence of this change in lipid composition of NAWM indicated an increase in the repulsive force between opposing bilayers that could explain decompaction and disruption of myelin structure

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

An overview of progress in electrolytes for secondary zinc-air batteries and other storage systems based on zinc

The revived interest and research on the development of novel energy storage systems with exceptional inherent safety, environmentally benign and low cost for integration in large scale electricity grid and electric vehicles is now driven by the global energy policies. Within various technical challenges yet to be resolved and despite extensive studies, the low cycle life of the zinc anode is still hindering the implementation of rechargeable zinc batteries at industrial scale. This review presents an extensive overview of electrolytes for rechargeable zinc batteries in relation to the anode issues which are closely affected by the electrolyte nature. Widely studied aqueous electrolytes, from alkaline to acidic pH, as well as non-aqueous systems including polymeric and room temperature ionic liquids are reported. References from early rechargeable Zn-air research to recent results on novel Zn hybrid systems have been analyzed. The ambition is to identify the challenges of the electrolyte system and to compile the proposed improvements and solutions. Ultimately, all the technologies based on zinc, including the more recently proposed novel zinc hybrid batteries combining the strong points of lithium-ion, redox-flow and metal-air systems, can benefit from this compilation in order to improve secondary zinc based batteries performance.Basque Country University (ZABALDUZ2012 program), and the Basque Country Government (Project: CIC energiGUNÉ16 of the ELKARTEK program) and the European Commission through the project ZAS: “Zinc Air Secondary innovative nanotech based batteries for efficient energy storage” (Grant Agreement 646186