Evaluation of ki-67 as independent risk factor and its role in the incidence of local recurrence/distant metastasis in luminal A and luminal B (her2 negative) breast cancer: a retrospective analysis from a single cancer center

Objective: We aimed to assess the relationship between the Ki-67 index and the risk of recur- rences and survival in patients with breast cancer (BC) that had positive estrogen receptor (ER), positive proges- terone receptor (PR), and negative human epidermal growth factor receptor (HER2). Patients and Methods: A total of 108 patients who visited the Clinical Oncology Department at Assuit Univer- sity Hospital between 2015 and 2018 were involved in the study. The level of Ki-67 was measured and patients were divided into low Ki-67 (n=62) and high Ki-67 (n=46) groups using 14% as the cut-off value. The Cox-regression hazard model was used for both Univariate and Multivariate analyses. Kaplan-Meier survival curves were used for the survival analysis. Results: Age, menopausal status, performance status (PS), pathological type, tumor stage (T), nodal stage (N), grade (G), and TNM stage were all analysed in relation to the Ki-67 index; the only statistically significant variable was the T stage (p=0.043). Patients with high Ki-67 level had a greater mortality rate than those with low levels (p=0.004). In comparison to low index groups, the mean disease free survival (DFS) and overall survival (OS) were lower in the high index groups (DFS: 48.41± 4.19 months vs. 64.53± 2.48 months and OS: 54.74± 3.59 months vs. 66.54± 1.99 months with p=0.001 and 0.002, respectively). When compared to the low index group, the high Ki-67 group had a significantly higher incidence of local recurrence (LR) and metastasis (p=0.001). Conclusions: In patients with positive ER/PR and HER2, negative HER2 BC, the level of Ki-67 strongly inversely correlates with LR/metastasis, DFS, and OS

Prevention of venous thromboembolism in acute spontaneous intracerebral haemorrhage: A survey of opinion

INTRODUCTION: People immobilized following acute spontaneous intracerebral haemorrhage (ICH) are at risk of venous thromboembolism (VTE) but the role of short-term prophylactic anticoagulation remains uncertain. We surveyed UK clinical practice and opinion regarding preventing VTE after ICH. PATIENTS AND METHODS: An online survey was sent to stroke healthcare professionals within the United Kingdom and Ireland via a professional society (British and Irish Association of Stroke Physicians (BIASP)). RESULTS: One hundred and twenty-three staff members responded to the survey, of whom 80% were consultant stroke physicians. All responders except one considered the issue to be important or extremely important, but only 5 (4%) were “extremely certain” and 51 (41%) “fairly certain” regarding the optimal treatment approach. Intermittent pneumatic compression (IPC) devices alone were the most used method (in 60%) followed by IPC devices and switching to low molecular weight heparin (LMWH) (in 30%). We identified high levels of uncertainty regarding the role of anticoagulation, and its optimal timing; uncertainty was greater in lobar compared to deep ICH. Most respondents (93%) consider a randomised controlled trial investigating the role of pharmacological VTE prophylaxis after acute ICH as important and would consider participation. DISCUSSION AND CONCLUSION: The optimal method for the prevention of VTE in non-traumatic ICH patients remains an area of clinical uncertainty. Clinical trials assessing short-term anticoagulation in patients after acute ICH would be beneficial in providing evidence to resolve this clinical dilemma

First results from the CRESST-III low-mass dark matter program

The CRESST experiment is a direct dark matter search which aims to measure interactions of potential dark matter particles in an earth-bound detector. With the current stage, CRESST-III, we focus on a low energy threshold for increased sensitivity towards light dark matter particles. In this manuscript we describe the analysis of one detector operated in the first run of CRESST-III (05/2016-02/2018) achieving a nuclear recoil threshold of 30.1eV. This result was obtained with a 23.6g CaWO$_4$ crystal operated as a cryogenic scintillating calorimeter in the CRESST setup at the Laboratori Nazionali del Gran Sasso (LNGS). Both the primary phonon/heat signal and the simultaneously emitted scintillation light, which is absorbed in a separate silicon-on-sapphire light absorber, are measured with highly sensitive transition edge sensors operated at ~15mK. The unique combination of these sensors with the light element oxygen present in our target yields sensitivity to dark matter particle masses as low as 160MeV/c$^2$.Comment: 9 pages, 9 figure

Regioselective protein oxidative cleavage enabled by enzyme-like recognition of an inorganic metal oxo cluster ligand

Oxidative modifications of proteins are key to many applications in biotechnology. Metal-catalyzed oxidation reactions efficiently oxidize proteins but with low selectivity, and are highly dependent on the protein surface residues to direct the reaction. Herein, we demonstrate that discrete inorganic ligands such as polyoxometalates enable an efficient and selective protein oxidative cleavage. In the presence of ascorbate (1 mM), the Cu-substituted polyoxometalate K8[Cu2+(H2O)(α2-P2W17O61)], (CuIIWD, 0.05 mM) selectively cleave hen egg white lysozyme under physiological conditions (pH =7.5, 37 °C) producing only four bands in the gel electropherogram (12.7, 11, 10, and 5 kDa). Liquid chromatography/mass spectrometry analysis reveals a regioselective cleavage in the vicinity of crystallographic CuIIWD/lysozyme interaction sites. Mechanistically, polyoxometalate is critical to position the Cu at the protein surface and limit the generation of oxidative species to the proximity of binding sites. Ultimately, this study outlines the potential of discrete, designable metal oxo clusters as catalysts for the selective modification of proteins through radical mechanisms under non-denaturing conditions

New limits on the resonant absorption of solar axions obtained with a 169^{169}Tm-containing cryogenic detector

A search for resonant absorption of solar axions by $^{169}$Tm nuclei was carried out. A newly developed approach involving low-background cryogenic bolometer based on Tm$_3$Al$_5$O$_{12}$ crystal was used that allowed for significant improvement of sensitivity in comparison with previous $^{169}$Tm based experiments. The measurements performed with $8.18$ g crystal during $6.6$ days exposure yielded the following limits on axion couplings: $|g_{A\gamma} (g_{AN}^0 + g_{AN}^3) \leq 1.44 \times 10^{-14}$ GeV$^{-1}$ and $|g_{Ae} (g_{AN}^0 + g_{AN}^3) \leq 2.81 \times 10^{-16}$.Comment: 7 pages, 5 figure