DEN: an R-Bioconductor based package to extract active sub-networks from human interaction map by integrating gene-expression data

Living cells are complex, dynamic, self-regulatory, interactive systems, showing differential states across time and space. Complexity of cellular systems is highlighted with the multi-layered regulatory mechanisms involving the interactions between bio-molecules (such as DNA, RNA, mi-RNA and proteins). These interactions are analyzed in the form of static networks. Likewise, number of experimental techniques like microarray, RNASeq allow quantification of cellular dynamics and aid in discerning differential gene expression across diverse conditions. Computational biology is in need of methods for integration of static networks and gene expression data, since it provides interesting insights into the dynamics of biological systems. DEN is an R/Bioconductor based package designed to assemble different types of human bio-molecular interactions as a complete interactome and contains functions to extract dynamic active networks by integration of gene expression data

Use of mechanical circulatory support devices among patients with acute myocardial infarction complicated by cardiogenic shock

Importance: Mechanical circulatory support (MCS) devices, including intravascular microaxial left ventricular assist devices (LVADs) and intra-aortic balloon pumps (IABPs), are used in patients who undergo percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) complicated by cardiogenic shock despite limited evidence of their clinical benefit. Objective: To examine trends in the use of MCS devices among patients who underwent PCI for AMI with cardiogenic shock, hospital-level use variation, and factors associated with use. Design, Setting, and Participants: This cross-sectional study used the CathPCI and Chest Pain-MI Registries of the American College of Cardiology National Cardiovascular Data Registry. Patients who underwent PCI for AMI complicated by cardiogenic shock between October 1, 2015, and December 31, 2017, were identified from both registries. Data were analyzed from October 2018 to August 2020. Exposures: Therapies to provide hemodynamic support were categorized as intravascular microaxial LVAD, IABP, TandemHeart, extracorporeal membrane oxygenation, LVAD, other devices, combined IABP and intravascular microaxial LVAD, combined IABP and other device (defined as TandemHeart, extracorporeal membrane oxygenation, LVAD, or another MCS device), or medical therapy only. Main Outcomes and Measures: Use of MCS devices overall and specific MCS devices, including intravascular microaxial LVAD, at both patient and hospital levels and variables associated with use. Results: Among the 28 304 patients included in the study, the mean (SD) age was 65.4 (12.6) years and 18 968 were men (67.0%). The overall MCS device use was constant from the fourth quarter of 2015 to the fourth quarter of 2017, although use of intravascular microaxial LVADs significantly increased (from 4.1% to 9.8%; P \u3c .001), whereas use of IABPs significantly decreased (from 34.8% to 30.0%; P \u3c .001). A significant hospital-level variation in MCS device use was found. The median (interquartile range [IQR]) proportion of patients who received MCS devices was 42% (30%-54%), and the median proportion of patients who received intravascular microaxial LVADs was 1% (0%-10%). In multivariable analyses, cardiac arrest at first medical contact or during hospitalization (odds ratio [OR], 1.82; 95% CI, 1.58-2.09) and severe left main and/or proximal left anterior descending coronary artery stenosis (OR, 1.36; 95% CI, 1.20-1.54) were patient characteristics that were associated with higher odds of receiving intravascular microaxial LVADs only compared with IABPs only. Conclusions and Relevance: This study found that, among patients who underwent PCI for AMI complicated by cardiogenic shock, overall use of MCS devices was constant, and a 2.5-fold increase in intravascular microaxial LVAD use was found along with a corresponding decrease in IABP use and a significant hospital-level variation in MCS device use. These trends were observed despite limited clinical trial evidence of improved outcomes associated with device use

Association of Cutibacterium acnes with human thyroid cancer

IntroductionThe diverse subtypes of thyroid carcinoma have distinct clinical outcomes despite a comparable spectrum of underlying genetic alterations. Beyond genetic alterations, sparse efforts have been made to characterize the microbes associated with thyroid cancer. In this study, we examine the microbial profile of thyroid cancer.MethodsWe sequenced the whole transcriptome of 70 thyroid cancers (40 papillary and 30 anaplastic). Using Infectious Pathogen Detector IPD 2.0, we analysed the relative abundance of 1060 microbes across 70 tumours from patients with thyroid cancer against 118 tumour samples from patients with breast, cervical, colorectal, and tongue cancer.ResultsOur analysis reveals a significant prevalence of Cutibacterium acnes in 58.6% thyroid cancer samples compared to other cancer types (p=0.00038). Immune cell fraction analysis between thyroid cancer samples with high and low Cutibacterium loads identify enrichment of immunosuppressive cells, including Tregs (p=0.015), and other anti-inflammatory cytokines in the tumour microenvironment, suggesting an immune evasion/immunosuppression milieu is associated with the infection. A higher burden of Cutibacterium acnes was also found to be associated with poor survival defining a distinct sub-group of thyroid cancer.ConclusionCutibacterium acnes is associated with immune suppression and poor prognosis in a subpopulation of thyroid cancer. This study may help design novel therapeutic measures involving appropriate antibiotics to manage the disease better

Multi-State Energy Classifier to Evaluate the Performance of the NILM Algorithm

With the large-scale deployment of smart meters worldwide, research in non-intrusive load monitoring (NILM) has seen a significant rise due to its dual use of real-time monitoring of end-user appliances and user-centric feedback of power consumption usage. NILM is a technique for estimating the state and the power consumption of an individual appliance in a consumer’s premise using a single point of measurement device such as a smart meter. Although there are several existing NILM techniques, there is no meaningful and accurate metric to evaluate these NILM techniques for multi-state devices such as the fridge, heat pump, etc. In this paper, we demonstrate the inadequacy of the existing metrics and propose a new metric that combines both event classification and energy estimation of an operational state to give a more realistic and accurate evaluation of the performance of the existing NILM techniques. In particular, we use unsupervised clustering techniques to identify the operational states of the device from a labeled dataset to compute a penalty threshold for predictions that are too far away from the ground truth. Our work includes experimental evaluation of the state-of-the-art NILM techniques on widely used datasets of power consumption data measured in a real-world environment

Mesopotamian morass: Identity and anti-imperialism in Iraq 1933–1941

Scholars have debated the nature and causes of nationalism in interwar Iraq since the end of the Second World War, with varying conclusions. One new school of thought presents a link between Nazi fascism and anti-Semitism and Iraqi nationalism. This thesis examines diplomatic, political, and intelligence documents regarding the Kingdom of Iraq from 1933 to 1941, bookended by the Simele Massacre and the Farhud. By linking these two terrible moments of violence with a diplomatic perspective of German, British, and Iraq relations, this study integrates proof of German ambivalence towards Arab nationalism with a simultaneous trend in anti-imperialist friction between Britain and Iraq. Certain minority groups, such as the Assyrians and the Iraqi Jews, found themselves associated with British imperialism, and this conflation of identity became the driving force behind the killings they encountered, not Nazi ideology. The study thus disassociates nationalism in Iraq from Nazi anti-Semitism and instead links it to resistance against continued British imperialism

Microwave-assisted synthesis of ß-amino alcohols

ß-amino alcohols are common substructures in many biologically active compounds and can also be used as catalysts for asymmetric reactions. One common method for forming these moieties is by ring opening of unsymmetrical epoxides using amines via a substitution reaction. However, the majority of these methods requires excess of reagents, inorganic initiators, and/or extended reaction times. We have developed an efficient, regioselective route to synthesize amino alcohols via microwave-assisted aminolysis of several hindered and unhindered epoxides using amine nucleophiles of varying strengths. Microwave reactions can be done without Lewis acids or promoters, even for the most hindered trisubstituted epoxides. In most of these cases, the reaction requires only a 1:1 ratio of amine to epoxide. Regioselectivity for the SN2 pathway can be increased in some reactions by decreasing the polarity of the solvent

Influence of the Choice of Disease Mapping Method on Population Characteristics in Areas of High Disease Burdens

Disease maps are powerful tools for depicting spatial variations in disease risk and its underlying drivers.  However, producing effective disease maps requires careful consideration of the statistical and spatial properties of the disease data. In fact, the choice of mapping method influences the resulting spatial pattern of the disease, as well as the understanding of its underlying population characteristics. New developments in mapping methods and software in addition to continuing improvements in data quality and quantity are requiring map-makers to make a multitude of decisions before a map of disease burdens can be created. The impact of such decisions on a map, including the choice of appropriate mapping method, not been addressed adequately in the literature. This research demonstrates how choice of mapping method and associated parameters influence the spatial pattern of disease. We use four different disease-mapping methods – unsmoothed choropleth maps, smoothed choropleth maps produced using the headbanging method, smoothed kernel density maps, and smoothed choropleth maps produced using spatial empirical Bayes methods and 5-years of zip code level HIV incidence (2007- 2011) data from Dallas and Tarrant Counties, Texas. For each map, the leading population characteristics and their relative importance with regards to HIV incidence is identified using a regression analysis of a CDC recommended list of socioeconomic determinants of HIV. Our results show that the choice of mapping method leads to different conclusions regarding the associations between HIV disease burden and the underlying demographic and socioeconomic characteristics. Thus, the choice of mapping method influences the patterns of disease we see or fail to see. Accurate depiction of areas of high disease burden is important for developing and targeting appropriate public health interventions

Domain-restricted mutation analysis to identify novel driver events in human cancer

Analysis of mutational spectra across various cancer types has given valuable insights into tumorigenesis. Different approaches have been used to identify novel drivers from the set of somatic mutations, including the methods which use sequence conservation, geometric localization and pathway information. Recent computational methods suggest use of protein domain information for analysis and understanding of the functional consequence of non-synonymous mutations. Similarly, evidence suggests recurrence at specific position in proteins is robust indicators of its functional impact. Building on this, we performed a systematic analysis of TCGA exome derived somatic mutations across 6089 PFAM domains and significantly mutated domains were identified using randomization approach. Multiple alignment of individual domain allowed us to prioritize for conserved residues mutated at analogous positions across different proteins in a statistically disciplined manner. In addition to the known frequently mutated genes, this analysis independently identifies low frequency Meprin and TRAF-Homology (MATH) domain in Speckle Type BTB/POZ (SPOP) protein, in prostate adenocarcinoma. Results from this analysis will help generate hypotheses about the downstream molecular mechanism resulting in cancer phenotypes

COMPARATIVE STUDIES OF NOVEL OXADIAZOLE DERIVATIVE HAVING CHIRAL CENTER ANDTHEIRANTI-MICROBIAL ACTIVITIES

Objective: To synthesize a series of (-) S & (+) S oxadiazole derivatives by the reaction of (-) (2S)-2-amino-2-(2-chlorophenyl) acetohydrazide & (+) (2S)-2-amino-2-(2-chloro phenyl) acetohydrazide with con. H2SO4, L(+) Tartaric acid, L(-) Tartaric acid, Hydrazine Hydrate, POCl3 and Various aromatic acid respectively. Methods: The structures of novel synthesized compounds have been established on the basis of elemental analysis, IR, 1H NMR, 13C NMR and mass spectral data and screened for their antibacterial and antifungal activities against different microorganisms by micro dilution method. Gentamycin, Ampicillin, Chloramphenicol, Ciprofloxacin, Norfloxacin, Nystatin, Greseofulvin were used as standard drugs for bacterial and fungus. Results: The newly synthesized compounds indicate that some of them show better antibacterial and antifungal activity than compared to their reference drug. Conclusion: Comparison of 1, 3, 4 oxadiazole having chiral center, characterized and exhibited promising antibacterial and antifungal activity