Marantic Endocarditis Associated with Pancreatic Cancer: A Case Series

Marantic endocarditis, otherwise known as nonbacterial thrombotic endocarditis (NBTE), is a well-documented phenomenon due to hypercoagulability from an underlying cause. It has been associated with a variety of inflammatory states including malignancy. Surprisingly, although hypercoagulability is often seen in patients with pancreatic cancer, marantic endocarditis has rarely been reported antemortem in this population. We report three cases of marantic endocarditis in patients with advanced pancreatic cancer. In two instances, the patients’ neurological symptoms preceded the diagnosis of advanced pancreatic cancer. Health care professionals should be alert to the possibility of marantic endocarditis in any patient with cancer, especially pancreatic cancer, who presents with symptoms of neurological dysfunction or an arterial thrombotic event. Prompt diagnosis and treatment with heparin, unfractionated or low molecular weight, may prevent catastrophic CNS events and decrease morbidity in patients with pancreatic cancer and other malignancies

Evaluation of pre-analytical factors affecting plasma DNA analysis.

Pre-analytical factors can significantly affect circulating cell-free DNA (cfDNA) analysis. However, there are few robust methods to rapidly assess sample quality and the impact of pre-analytical processing. To address this gap and to evaluate effects of DNA extraction methods and blood collection tubes on cfDNA yield and fragment size, we developed a multiplexed droplet digital PCR (ddPCR) assay with 5 short and 4 long amplicons targeting single copy genomic loci. Using this assay, we compared 7 cfDNA extraction kits and found cfDNA yield and fragment size vary significantly. We also compared 3 blood collection protocols using plasma samples from 23 healthy volunteers (EDTA tubes processed within 1 hour and Cell-free DNA Blood Collection Tubes processed within 24 and 72 hours) and found no significant differences in cfDNA yield, fragment size and background noise between these protocols. In 219 clinical samples, cfDNA fragments were shorter in plasma samples processed immediately after venipuncture compared to archived samples, suggesting contribution of background DNA by lysed peripheral blood cells. In summary, we have described a multiplexed ddPCR assay to assess quality of cfDNA samples prior to downstream molecular analyses and we have evaluated potential sources of pre-analytical variation in cfDNA studies

Automated segmentation of tissue images for computerized IHC analysis

This paper presents two automated methods for the segmentation ofimmunohistochemical tissue images that overcome the limitations of themanual approach aswell as of the existing computerized techniques. The first independent method, based on unsupervised color clustering, recognizes automatically the target cancerous areas in the specimen and disregards the stroma; the second method, based on colors separation and morphological processing, exploits automated segmentation of the nuclear membranes of the cancerous cells. Extensive experimental results on real tissue images demonstrate the accuracy of our techniques compared to manual segmentations; additional experiments show that our techniques are more effective in immunohistochemical images than popular approaches based on supervised learning or active contours. The proposed procedure can be exploited for any applications that require tissues and cells exploration and to perform reliable and standardized measures of the activity of specific proteins involved in multi-factorial genetic pathologie

Effect of various fluxes on different metals and alloys in A-TIG process: a review

Welding is the process of coalescence of two metals/alloys for creating a seamless joint, is a quintessential fabrication process utilised in almost every manufacturing sector. There is a range of welding processes that are used according to their features and the requirement of the fabricator. The tungsten inert gas (TIG) welding process is an extensively used welding process owing to its inherent characteristics like high weld quality, surface cleanliness, and autogenous welding mode. Unfortunately, the TIG process suffers some drawbacks, the most pronounced one is the shallow weld bead and low depth of penetration (DOP). This renders the process unusable for welding thicker sections in a single pass and consequently requires multiple passes which adds to the expenditure. A modification to this process is the A-TIG welding where A stands for Activated, the method utilises activating flux material to augment the penetration depth and depth to width ratio (DWR) of the weld bead. The current work is comprehensive and focuses mainly on the basics of the A-TIG process, understanding of weld pool dynamics that are governing the depth of penetration, analysis of various flux materials for their effects on different metals/alloys and finally the outcomes fetched from using A-TIG process on different commercially important alloys

Adenoma thyroid with supraclavicular tuberculous lymphadenitis Masquerading as malignancy thyroid with Metastasis - Diagnostic dilemma

Abstract: Thyroid swelling or goitre is one of the commonest presentations among female patients more than males attending ENT out patients. The clinical importance of thyroid swelling is related to evaluating their functional status and assess,whether it is benign,malignant ,hypo or hyper active.Even if benign should look for pressure symptoms which justifies surgery.Tuberculous lymphadenitis is the most common form of extrapulmonary tuberculosis.Coexistence of thyroid swelling with supraclavicular lymph node mimicking malignancy with metastatic deposit is unusual and always to be evaluated. We report a case of a 45-year female,who on outside initial evaluation was diagnosed as follicular carcinoma of thyroid. However clinical examination revealed a palpable supraclavicular lymph node. Thus subjected to a repeat FNA (fine needle aspiration) from thyroid which revealed benign thyroid follicular adenoma and FNA from supraclavicular lymph node revealed tuberculous lymphadenitis, which was further confirmed by histological sections post operatively. This case emphasizes the need for thorough clinical examination and utility of image guided FNA to rule out the biological nature of these lesion

Surface defects incorporated diamond machining of silicon

Abstract This paper reports the performance enhancement benefits in diamond turning of the silicon wafer by incorporation of the surface defect machining (SDM) method. The hybrid micromachining methods usually require additional hardware to leverage the added advantage of hybrid technologies such as laser heating, cryogenic cooling, electric pulse or ultrasonic elliptical vibration. The SDM method tested in this paper does not require any such additional baggage and is easy to implement in a sequential micro-machining mode. This paper made use of Raman spectroscopy data, average surface roughness data and imaging data of the cutting chips of silicon for drawing a comparison between conventional single-point diamond turning (SPDT) and SDM while incorporating surface defects in the (i) circumferential and (ii) radial directions. Complementary 3D finite element analysis (FEA) was performed to analyse the cutting forces and the evolution of residual stress on the machined wafer. It was found that the surface defects generated in the circumferential direction with an interspacing of 1 mm revealed the lowest average surface roughness (Ra) of 3.2 nm as opposed to 8 nm Ra obtained through conventional SPDT using the same cutting parameters. The observation of the Raman spectroscopy performed on the cutting chips showed remnants of phase transformation during the micromachining process in all cases. FEA was used to extract quantifiable information about the residual stress as well as the sub-surface integrity and it was discovered that the grooves made in the circumferential direction gave the best machining performance. The information being reported here is expected to provide an avalanche of opportunities in the SPDT area for low-cost machining solution for a range of other nominal hard, brittle materials such as SiC, ZnSe and GaAs as well as hard steels.</jats:p

Cell-specific occupancy dynamics between the pioneer-like factor Opa/ZIC and Ocelliless/OTX regulate early head development in embryos

During development, embryonic patterning systems direct a set of initially uncommitted pluripotent cells to differentiate into a variety of cell types and tissues. A core network of transcription factors, such as Zelda/POU5F1, Odd-paired (Opa)/ZIC3 and Ocelliless (Oc)/OTX2, are conserved across animals. While Opa is essential for a second wave of zygotic activation after Zelda, it is unclear whether Opa drives head cell specification, in the Drosophila embryo. Our hypothesis is that Opa and Oc are interacting with distinct cis-regulatory regions for shaping cell fates in the embryonic head. Super-resolution microscopy and meta-analysis of single-cell RNAseq datasets show that opa’s and oc’s overlapping expression domains are dynamic in the head region, with both factors being simultaneously transcribed at the blastula stage. Additionally, analysis of single-embryo RNAseq data reveals a subgroup of Opa-bound genes to be Opa-independent in the cellularized embryo. Interrogation of these genes against Oc ChIPseq combined with in situ data, suggests that Opa is competing with Oc for the regulation of a subgroup of genes later in gastrulation. Specifically, we find that Oc binds to late, head-specific enhancers independently and activates them in a head-specific wave of zygotic transcription, suggesting distinct roles for Oc in the blastula and gastrula stages

Anticancer efficacy of the hypoxia-activated prodrug evofosfamide is enhanced in combination with proapoptotic receptor agonists against osteosarcoma

Tumor hypoxia is a major cause of treatment failure for a variety of malignancies. However, hypoxia also leads to treatment opportunities as demonstrated by the development of compounds that target regions of hypoxia within tumors. Evofosfamide is a hypoxia-activated prodrug that is created by linking the hypoxia-seeking 2-nitroimidazole moiety to the cytotoxic bromo-isophosphoramide mustard (Br-IPM). When evofosfamide is delivered to hypoxic regions of tumors, the DNA cross-linking toxin, Br-IPM, is released leading to cell death. This study assessed the anticancer efficacy of evofosfamide in combination with the Proapoptotic Receptor Agonists (PARAs) dulanermin and drozitumab against human osteosarcoma in vitro and in an intratibial murine model of osteosarcoma. Under hypoxic conditions in vitro, evofosfamide cooperated with dulanermin and drozitumab, resulting in the potentiation of cytotoxicity to osteosarcoma cells. In contrast, under the same conditions, primary human osteoblasts were resistant to treatment. Animals transplanted with osteosarcoma cells directly into their tibiae developed mixed osteosclerotic/osteolytic bone lesions and consequently developed lung metastases 3 weeks post cancer cell transplantation. Tumor burden in the bone was reduced by evofosfamide treatment alone and in combination with drozitumab and prevented osteosarcoma-induced bone destruction while also reducing the growth of pulmonary metastases. These results suggest that evofosfamide may be an attractive therapeutic agent, with strong anticancer activity alone or in combination with either drozitumab or dulanermin against osteosarcoma.Vasilios Liapis, Aneta Zysk, Mark DeNichilo, Irene Zinonos, Shelley Hay, Vasilios Panagopoulos, Alexandra Shoubridge, Christopher Difelice, Vladimir Ponomarev, Wendy Ingman, Gerald J. Atkins, David M. Findlay, Andrew C. W. Zannettino and Andreas Evdokio