Bilateral phyllodes tumor of the breast in a young nulliparous woman

Cystosarcoma phyllodes is a rare breast tumor with incidence of 1% of all the mammary tumors. Bilateral occurrence is very rare. Median age of presentation is 40-50 years. We present a case of 24 years old nulliparous female with phyllodes tumour developing in both the breasts one after another with a gap of five years. Patient underwent simple mastectomy on both sides. Histopathology report confirmed benign variety of cystosarcoma phyllodes on both sides

Clinical profile and factors associated with microalbuminuria in type 1 diabetes mellitus in children and adolescents

Background: The aim of this study was to determine the pattern of clinical presentation and factor associated with microalbuminuria.Methods: Urinary albumin excretion of children and adolescents diagnosed with type 1 diabetes mellitus attending diabetic clinic of Katihar medical college hospital over a period of one year. Collected blood and urine samples were analysed for glycated haemoglobin, cholesterol, triglycerides, and for 12 hour urinary albumin concentration. Blood pressures were recorded and clinical data collected.Results: During the study period 215 patients were diagnosed with type1 DM. Out of 215, fourty-three patients (20%) had persistent microalbuminuria. Factor associated with microalbuminuria in diabetic patients include duration of diabetes mellitus, higher blood pressure, higher cholesterol and triglyceride levels.Conclusion: Type 1 DM is treatable and testing is acceptable and accessible to the patients. As microalbuminuria is an early microvascular complications, it is highly recommended to screen all diabetic patients for the incidence of microalbuminuria and modifiable risk factors like dyslipidemia at the onset and then yearly assessment. Efforts need to be intensified in education of health workers and population at large for quick presentation and prompt diagnosis in order to predict overt diabetic nephropathy and also to prevent its progression.

A Strategy for LSST to Unveil a Population of Kilonovae without Gravitational-wave Triggers

We present a cadence optimization strategy to unveil a large population of kilonovae using optical imaging alone. These transients are generated during binary neutron star and potentially neutron star–black hole mergers and are electromagnetic counterparts to gravitational-wave signals detectable in nearby events with Advanced LIGO, Advanced Virgo, and other interferometers that will be online in the near future. Discovering a large population of kilonovae will allow us to determine how heavy-element production varies with the intrinsic parameters of the merger and across cosmic time. The rate of binary neutron star mergers is still uncertain, but only few (≾ 15) events with associated kilonovae may be detectable per year within the horizon of next-generation ground-based interferometers. The rapid evolution (~days) at optical/infrared wavelengths, relatively low luminosity, and the low volumetric rate of kilonovae makes their discovery difficult, especially during blind surveys of the sky. We propose future large surveys to adopt a rolling cadence in which g-i observations are taken nightly for blocks of 10 consecutive nights. With the current baseline2018a cadence designed for the Large Synoptic Survey Telescope (LSST), l≾ 7.5 poorly sampled kilonovae are expected to be detected in both the Wide Fast Deep (WFD) and Deep Drilling Fields (DDF) surveys per year, under optimistic assumptions on their rate, duration, and luminosity. We estimate the proposed strategy to return up to ~272 GW170817-like kilonovae throughout the LSST WFD survey, discovered independently from gravitational-wave triggers

Chemical Distribution of the Dynamical Ejecta in the Neutron Star Merger GW170817

GW170817 and its associated electromagnetic counterpart AT2017gfo continue to be a treasure trove as observations and modeling continue. Recent precision astrometry of AT2017gfo with the Hubble Space Telescope combined with previous constraints from Very Long Baseline Interferometry (VLBI) constraints narrowed down the inclination angle to 19-25 deg (90\% confidence). This paper explores how the inclusion of precise inclination information can reveal new insights about the ejecta properties, in particular, about the composition of the dynamical ejecta of AT2017gfo. Our analysis relies on updated kilonova modeling, which includes state-of-the-art heating rates, thermalization efficiencies, and opacities and is parameterized by $\bar{Y}_{\rm e,dyn}$, the average electron fraction of the dynamical ejecta component. Using this model, we incorporate the latest inclination angle constraint of AT2017gfo into a light curve fitting framework to derive updated parameter estimates. Our results suggest that the viewing angle of the observer is pointed towards the lanthanide-poor ($Y_{\rm e,dyn}\gtrsim0.25$), squeezed polar dynamical ejecta component, which can explain the early blue emission observed in the light curve of AT2017gfo. In contrast to a recent claim of spherical ejecta powering AT2017gfo, our study indicates that the composition of the dynamical ejecta has a strong angular dependence, with a lanthanide-rich ($Y_{\rm e,dyn}\lesssim0.25$), tidal component distributed around the merger plane with a half-opening angle of $35^\circ$. The inclination angle constraint reduces $\bar{Y}_{\rm e,dyn}$ from $0.24$ to $0.22$, with values $0.17\lesssim Y_{\rm e, dyn} \lesssim0.41$ enabling the robust production of $r$-process elements up to the $3^{\rm rd}$ peak in the tidal dynamical ejecta.Comment: 8 pages, 6 figure

Virmid: accurate detection of somatic mutations with sample impurity inference

Detection of somatic variation using sequence from disease-control matched data sets is a critical first step. In many cases including cancer, however, it is hard to isolate pure disease tissue, and the impurity hinders accurate mutation analysis by disrupting overall allele frequencies. Here, we propose a new method, Virmid, that explicitly determines the level of impurity in the sample, and uses it for improved detection of somatic variation. Extensive tests on simulated and real sequencing data from breast cancer and hemimegalencephaly demonstrate the power of our model. A software implementation of our method is available at http://sourceforge.net/projects/virmid/

Reprogramming of bivalent chromatin states in NRAS mutant melanoma suggests PRC2 inhibition as a therapeutic strategy.

The dynamic evolution of chromatin state patterns during metastasis, their relationship with bona fide genetic drivers, and their therapeutic vulnerabilities are not completely understood. Combinatorial chromatin state profiling of 46 melanoma samples reveals an association of NRAS mutants with bivalent histone H3 lysine 27 trimethylation (H3K27me3) and Polycomb repressive complex 2. Reprogramming of bivalent domains during metastasis occurs on master transcription factors of a mesenchymal phenotype, including ZEB1, TWIST1, and CDH1. Resolution of bivalency using pharmacological inhibition of EZH2 decreases invasive capacity of melanoma cells and markedly reduces tumor burden in vivo, specifically in NRAS mutants. Coincident with bivalent reprogramming, the increased expression of pro-metastatic and melanocyte-specific cell-identity genes is associated with exceptionally wide H3K4me3 domains, suggesting a role for this epigenetic element. Overall, we demonstrate that reprogramming of bivalent and broad domains represents key epigenetic alterations in metastatic melanoma and that EZH2 plus MEK inhibition may provide a promising therapeutic strategy for NRAS mutant melanoma patients

A Strategy for LSST to Unveil a Population of Kilonovae without Gravitational-wave Triggers

We present a cadence optimization strategy to unveil a large population of kilonovae using optical imaging alone. These transients are generated during binary neutron star and potentially neutron star–black hole mergers and are electromagnetic counterparts to gravitational-wave signals detectable in nearby events with Advanced LIGO, Advanced Virgo, and other interferometers that will be online in the near future. Discovering a large population of kilonovae will allow us to determine how heavy-element production varies with the intrinsic parameters of the merger and across cosmic time. The rate of binary neutron star mergers is still uncertain, but only few (≾ 15) events with associated kilonovae may be detectable per year within the horizon of next-generation ground-based interferometers. The rapid evolution (~days) at optical/infrared wavelengths, relatively low luminosity, and the low volumetric rate of kilonovae makes their discovery difficult, especially during blind surveys of the sky. We propose future large surveys to adopt a rolling cadence in which g-i observations are taken nightly for blocks of 10 consecutive nights. With the current baseline2018a cadence designed for the Large Synoptic Survey Telescope (LSST), l≾ 7.5 poorly sampled kilonovae are expected to be detected in both the Wide Fast Deep (WFD) and Deep Drilling Fields (DDF) surveys per year, under optimistic assumptions on their rate, duration, and luminosity. We estimate the proposed strategy to return up to ~272 GW170817-like kilonovae throughout the LSST WFD survey, discovered independently from gravitational-wave triggers

Enhancer Reprogramming Confers Dependence on Glycolysis and IGF Signaling in KMT2D Mutant Melanoma.

Histone methyltransferase KMT2D harbors frequent loss-of-function somatic point mutations in several tumor types, including melanoma. Here, we identify KMT2D as a potent tumor suppressor in melanoma through an in vivo epigenome-focused pooled RNAi screen and confirm the finding by using a genetically engineered mouse model (GEMM) based on conditional and melanocyte-specific deletion of KMT2D. KMT2D-deficient tumors show substantial reprogramming of key metabolic pathways, including glycolysis. KMT2D deficiency aberrantly upregulates glycolysis enzymes, intermediate metabolites, and glucose consumption rates. Mechanistically, KMT2D loss causes genome-wide reduction of H3K4me1-marked active enhancer chromatin states. Enhancer loss and subsequent repression of IGFBP5 activates IGF1R-AKT to increase glycolysis in KMT2D-deficient cells. Pharmacological inhibition of glycolysis and insulin growth factor (IGF) signaling reduce proliferation and tumorigenesis preferentially in KMT2D-deficient cells. We conclude that KMT2D loss promotes tumorigenesis by facilitating an increased use of the glycolysis pathway for enhanced biomass needs via enhancer reprogramming, thus presenting an opportunity for therapeutic intervention through glycolysis or IGF pathway inhibitors