11,145 research outputs found
MicroRNA-330-5p as a putative modulator of neoadjuvant chemoradiotherapy sensitivity in oesophageal adenocarcinoma
Oesophageal adenocarcinoma (OAC) is the sixth most common cause of cancer deaths worldwide, and the 5-year survival rate for patients diagnosed with the disease is approximately 17%. The standard of care for locally advanced disease is neoadjuvant chemotherapy or, more commonly, combined neoadjuvant chemoradiation therapy (neo-CRT) prior to surgery. Unfortunately, ~60-70% of patients will fail to respond to neo-CRT. Therefore, the identification of biomarkers indicative of patient response to treatment has significant clinical implications in the stratification of patient treatment. Furthermore, understanding the molecular mechanisms underpinning tumour response and resistance to neo-CRT will contribute towards the identification of novel therapeutic targets for enhancing OAC sensitivity to CRT. MicroRNAs (miRNA/miR) function to regulate gene and protein expression and play a causal role in cancer development and progression. MiRNAs have also been identified as modulators of key cellular pathways associated with resistance to CRT. Here, to identify miRNAs associated with resistance to CRT, pre-treatment diagnostic biopsy specimens from patients with OAC were analysed using miRNA-profiling arrays. In pre-treatment biopsies miR-330-5p was the most downregulated miRNA in patients who subsequently failed to respond to neo-CRT. The role of miR-330 as a potential modulator of tumour response and sensitivity to CRT in OAC was further investigated in vitro. Through vector-based overexpression the E2F1/p-AKT survival pathway, as previously described, was confirmed as a target of miR-330 regulation. However, miR-330-mediated alterations to the E2F1/p-AKT pathway were insufficient to significantly alter cellular sensitivity to chemotherapy (cisplatin and 5-flurouracil). In contrast, silencing of miR-330-5p enhanced, albeit subtly, cellular resistance to clinically relevant doses of radiation. This study highlights the need for further investigation into the potential of miR-330-5p as a predictive biomarker of patient sensitivity to neo-CRT and as a novel therapeutic target for manipulating cellular sensitivity to neo-CRT in patients with OAC
A Viking burial at Balnakeil, Sutherland
A full discussion of a young Viking male pagan grave with full consideration of its context and broader significance in the context of the Norse in the British Isles
Altered expression of caspases-4 and -5 during inflammatory bowel disease and colorectal cancer : diagnostic and therapeutic potential
Caspases are a group of proteolytic enzymes involved in the co-ordination of cellular processes, including cellular homeostasis, inflammation and apoptosis. Altered activity of caspases, particularly caspase-1, has been implicated in the development of intestinal diseases, such as inflammatory bowel disease (IBD) and colorectal cancer (CRC). However, the involvement of two related inflammatory caspase members, caspases-4 and -5, during intestinal homeostasis and disease has not yet been established. This study demonstrates that caspases-4 and -5 are involved in IBD-associated intestinal inflammation. Furthermore, we found a clear correlation between stromal caspase-4 and -5 expression levels, inflammation and disease activity in ulcerative colitis patients. Deregulated intestinal inflammation in IBD patients is associated with an increased risk of developing CRC. We found robust expression of caspases-4 and -5 within intestinal epithelial cells, exclusively within neoplastic tissue, of colorectal tumours. An examination of adjacent normal, inflamed and tumour tissue from patients with colitis-associated CRC confirmed that stromal expression of caspases-4 and -5 is increased in inflamed and dysplastic tissue, while epithelial expression is restricted to neoplastic tissue. In addition to identifying caspases-4 and -5 as potential targets for limiting intestinal inflammation, this study has identified epithelial-expressed caspases-4 and -5 as biomarkers with diagnostic and therapeutic potential in CRC
Is the timed-up and go test feasible in mobile devices? A systematic review
The number of older adults is increasing worldwide, and it is expected that by 2050 over 2 billion individuals will be more than 60 years old. Older adults are exposed to numerous pathological problems such as Parkinson’s disease, amyotrophic lateral sclerosis, post-stroke, and orthopedic disturbances. Several physiotherapy methods that involve measurement of movements, such as the Timed-Up and Go test, can be done to support efficient and effective evaluation of pathological symptoms and promotion of health and well-being. In this systematic review, the authors aim to determine how the inertial sensors embedded in mobile devices are employed for the measurement of the different parameters involved in the Timed-Up and Go test. The main contribution of this paper consists of the identification of the different studies that utilize the sensors available in mobile devices for the measurement of the results of the Timed-Up and Go test. The results show that mobile devices embedded motion sensors can be used for these types of studies and the most commonly used sensors are the magnetometer, accelerometer, and gyroscope available in off-the-shelf smartphones. The features analyzed in this paper are categorized as quantitative, quantitative + statistic, dynamic balance, gait properties, state transitions, and raw statistics. These features utilize the accelerometer and gyroscope sensors and facilitate recognition of daily activities, accidents such as falling, some diseases, as well as the measurement of the subject's performance during the test execution.info:eu-repo/semantics/publishedVersio
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A semantic Grid for molecular science
Proceedings of the 2003 UK e-Science All Hands Meeting, 31st August - 3rd September, Nottingham UKThe properties of molecules have very well defined semantics and allow the creation of a semantic GRID. Markup languages (CML - Chemical Markup Language) and dictionary-based ontologies have been designed to support a wide range of applications, including chemical supply, publication and the safety of compounds. Many properties can be computed by Quantum Mechanical (QM) programs and we have developed a "black-box" system based on XML wrappers for all components. This is installed on a Condor system on which we have computed properties for 250, 000 compounds. The results of this will be available in an OpenData/OpenSource peer-to-peer (P2P) system (WorldWide Molecular Matrix - WWMM)
Detection of Pathological HFO Using Supervised Machine Learning and iEEG Data
Epilepsy is the second most common neurological disorder and it affects approxi mately 50 million people worldwide. One of the main characteristics of this disorder is the presence of recurrent seizures which tend to be controlled through medication. Nonetheless, 20% of the patients with this disorder are resistant to drug treatment meaning that they need to go through alternative procedures
‘Do you see what I see?’ Medical imaging: the interpretation of visual information
Röntgen's discovery of x-rays in 1895, gave to medicine the extraordinary benefit of being able to see inside the living body without surgery. Over time, technology has added to the sophistication of imaging processes in medicine and we now have a wide range of techniques at our disposal for the investigation and early detection of disease. But radiology deals with visual information; and like any information this requires interpretation. It is a practical field and medical images are used to make inferences about the state of peoples' health. These inferences are subject to the same variability and error as any decision-making process and so the criteria for the success of medical imaging are based not entirely on the images themselves but on the performance of the decision-makers. Research in the accuracy of medical imaging must draw on techniques from a wide range of disciplines including physics, psychology, computing, neuroscience and medicine in attempting to better understand the processes involved in visual decision-making in this context and to minimise diagnostic error
An analytical connection between temporal and spatio-temporal growth rates in linear stability analysis
We derive an exact formula for the complex frequency in spatio-temporal
stability analysis that is valid for arbitrary complex wave numbers. The
usefulness of the formula lies in the fact that it depends only on purely
temporal quantities, which are easily calculated. We apply the formula to two
model dispersion relations: the linearized complex Ginzburg--Landau equation,
and a model of wake instability. In the first case, a quadratic truncation of
the exact formula applies; in the second, the same quadratic truncation yields
an estimate of the parameter values at which the transition to absolute
instability occurs; the error in the estimate decreases upon increasing the
order of the truncation. We outline ways in which the formula can be used to
characterize stability results obtained from purely numerical calculations, and
point to a further application in global stability analyses.Comment: 36 pages, 16 figures; Article has been tweaked and reduced in size
but essential features remain the same; Supplementary material (16 pages) is
also include
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